sha,source_x,title,doi,pmcid,pubmed_id,license,abstract,publish_time,authors,journal,Microsoft Academic Paper ID,WHO #Covidence,has_full_text
c630ebcdf30652f0422c3ec12a00b50241dc9bd9,CZI,Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target,10.1007/s00134-020-05985-9,,32125455,cc-by-nc,,2020,"Zhang, Haibo; Penninger, Josef M.; Li, Yimin; Zhong, Nanshan; Slutsky, Arthur S.",Intensive Care Med,2002765492,#3252,True
53eccda7977a31e3d0f565c884da036b1e85438e,CZI,Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations,10.1038/s41421-020-0147-1,,,cc-by,,2020,"Cao, Yanan; Li, Lin; Feng, Zhimin; Wan, Shengqing; Huang, Peide; Sun, Xiaohui; Wen, Fang; Huang, Xuanlin; Ning, Guang; Wang, Weiqing",Cell Discovery,3003430844,#1861,True
210a892deb1c61577f6fba58505fd65356ce6636,CZI,Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data,10.3390/jcm9020538,,,cc-by,"The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the incubation period and other time intervals that govern the epidemiological dynamics of COVID-19 infections. Our results show that the incubation period falls within the range of 2–14 days with 95% confidence and has a mean of around 5 days when approximated using the best-fit lognormal distribution. The mean time from illness onset to hospital admission (for treatment and/or isolation) was estimated at 3–4 days without truncation and at 5–9 days when right truncated. Based on the 95th percentile estimate of the incubation period, we recommend that the length of quarantine should be at least 14 days. The median time delay of 13 days from illness onset to death (17 days with right truncation) should be considered when estimating the COVID-19 case fatality risk.",2020,"Linton, M. Natalie; Kobayashi, Tetsuro; Yang, Yichi; Hayashi, Katsuma; Akhmetzhanov, R. Andrei; Jung, Sung-mok; Yuan, Baoyin; Kinoshita, Ryo; Nishiura, Hiroshi",Journal of Clinical Medicine,3006065484,#1043,True
e3b40cc8e0e137c416b4a2273a4dca94ae8178cc,CZI,Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China,10.3390/jcm9020575,,32093211,cc-by,"In December 2019, cases of unidentified pneumonia with a history of exposure in the Huanan Seafood Market were reported in Wuhan, Hubei Province. A novel coronavirus, SARS-CoV-2, was identified to be accountable for this disease. Human-to-human transmission is confirmed, and this disease (named COVID-19 by World Health Organization (WHO)) spread rapidly around the country and the world. As of 18 February 2020, the number of confirmed cases had reached 75,199 with 2009 fatalities. The COVID-19 resulted in a much lower case-fatality rate (about 2.67%) among the confirmed cases, compared with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Among the symptom composition of the 45 fatality cases collected from the released official reports, the top four are fever, cough, short of breath, and chest tightness/pain. The major comorbidities of the fatality cases include hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic bronchitis. The source of the virus and the pathogenesis of this disease are still unconfirmed. No specific therapeutic drug has been found. The Chinese Government has initiated a level-1 public health response to prevent the spread of the disease. Meanwhile, it is also crucial to speed up the development of vaccines and drugs for treatment, which will enable us to defeat COVID-19 as soon as possible.",2020,"Deng, Sheng-Qun; Peng, Hong-Juan",J Clin Med,177663115,#1999,True
92c2c9839304b4f2bc1276d41b1aa885d8b364fd,CZI,Imaging changes in severe COVID-19 pneumonia,10.1007/s00134-020-05976-w,,32125453,cc-by-nc,,2020,"Zhang, Wei",Intensive Care Med,3006643024,#3242,False
0df0d5270a9399cf4e23c0cdd877a80616a9725e,CZI,An updated estimation of the risk of transmission of the novel coronavirus (2019-nCov),10.1016/j.idm.2020.02.001,,,cc-by-nc-nd,"The basic reproduction number of an infectious agent is the average number of infections one case can generate over the course of the infectious period, in a naïve, uninfected population. It is well-known that the estimation of this number may vary due to several methodological issues, including different assumptions and choice of parameters, utilized models, used datasets and estimation period. With the spreading of the novel coronavirus (2019-nCoV) infection, the reproduction number has been found to vary, reflecting the dynamics of transmission of the coronavirus outbreak as well as the case reporting rate. Due to significant variations in the control strategies, which have been changing over time, and thanks to the introduction of detection technologies that have been rapidly improved, enabling to shorten the time from infection/symptoms onset to diagnosis, leading to faster confirmation of the new coronavirus cases, our previous estimations on the transmission risk of the 2019-nCoV need to be revised. By using time-dependent contact and diagnose rates, we refit our previously proposed dynamics transmission model to the data available until January 29th 2020 and re-estimated the effective daily reproduction ratio that better quantifies the evolution of the interventions. We estimated when the effective daily reproduction ratio has fallen below 1 and when the epidemics will peak. Our updated findings suggest that the best measure is persistent and strict self-isolation. The epidemics will continue to grow, and can peak soon with the peak time depending highly on the public health interventions practically implemented.",2020,"Tang, Biao; Bragazzi, Nicola Luigi; Li, Qian; Tang, Sanyi; Xiao, Yanni; Wu, Jianhong",Infectious Disease Modelling,3006028839,#729,True
f24242580be243d5fc3f432915d86af6854bb8b7,CZI,"Real-time forecasts of the 2019-nCoV epidemic in China from February 5th to February 24th, 2020",10.1016/j.idm.2020.02.002,,,cc-by-nc-nd,"The initial cluster of severe pneumonia cases that triggered the 2019-nCoV epidemic was identified in Wuhan, China in December 2019. While early cases of the disease were linked to a wet market, human-to-human transmission has driven the rapid spread of the virus throughout China. The Chinese government has implemented containment strategies of city-wide lockdowns, screening at airports and train stations, and isolation of suspected patients; however, the cumulative case count keeps growing every day. The ongoing outbreak presents a challenge for modelers, as limited data are available on the early growth trajectory, and the epidemiological characteristics of the novel coronavirus are yet to be fully elucidated. We use phenomenological models that have been validated during previous outbreaks to generate and assess short-term forecasts of the cumulative number of confirmed reported cases in Hubei province, the epicenter of the epidemic, and for the overall trajectory in China, excluding the province of Hubei. We collect daily reported cumulative case data for the 2019-nCoV outbreak for each Chinese province from the National Health Commission of China. Here, we provide 5, 10, and 15 day forecasts for five consecutive days, February 5th through February 9th, with quantified uncertainty based on a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model. Our most recent forecasts reported here based on data up until February 9, 2020, largely agree across the three models presented and suggest an average range of 7,409 – 7,496 additional cases in Hubei and 1,128 – 1,929 additional cases in other provinces within the next five days. Models also predict an average total cumulative case count between 37,415 – 38,028 in Hubei and 11,588 – 13,499 in other provinces by February 24, 2020. Mean estimates and uncertainty bounds for both Hubei and other provinces have remained relatively stable in the last three reporting dates (February 7th – 9th). We also observe that each of the models predicts that the epidemic has reached saturation in both Hubei and other provinces. Our findings suggest that the containment strategies implemented in China are successfully reducing transmission and that the epidemic growth has slowed in recent days.",2020,"Roosa, K.; Lee, Y.; Luo, R.; Kirpich, A.; Rothenberg, R.; Hyman, J. M.; Yan, P.; Chowell, G.",Infectious Disease Modelling,3006028741,#865,True
d13a685f861b0f1ba05afa6e005311ad1820fd3a,CZI,RETRACTED: Chinese medical staff request international medical assistance in fighting against COVID-19,10.1016/s2214-109x(20)30065-6,,32105614,cc-by,,2020,"Zeng, Yingchun; Zhen, Yan",The Lancet. Global health,2627046314,#5386,False
e1b336d8be1a4c0ccc5a1bf41e48b3b004d3ece1,CZI,COVID-19 outbreak on the Diamond Princess cruise ship: estimating the epidemic potential and effectiveness of public health countermeasures,10.1093/jtm/taaa030,,,cc-by-nc,"Cruise ships carry a large number of people in confined spaces with relative homogeneous mixing. On 3 February, 2020, an outbreak of COVID-19 on cruise ship Diamond Princess was reported with 10 initial cases, following an index case on board around 21-25 January. By 4 February, public health measures such as removal and isolation of ill passengers and quarantine of non-ill passengers were implemented. By 20 February, 619 of 3,700 passengers and crew (17%) were tested positive.We estimated the basic reproduction number from the initial period of the outbreak using (SEIR) models. We calibrated the models with transient functions of countermeasures to incidence data. We additionally estimated a counterfactual scenario in absence of countermeasures, and established a model stratified by crew and guests to study the impact of differential contact rates among the groups. We also compared scenarios of an earlier versus later evacuation of the ship.The basic reproduction rate was initially 4 times higher on-board compared to the ${R}_0$ in the epicentre in Wuhan, but the countermeasures lowered it substantially. Based on the modeled initial ${R}_0$ of 14.8, we estimated that without any interventions within the time period of 21 January to 19 February, 2920 out of the 3700 (79%) would have been infected. Isolation and quarantine therefore prevented 2307 cases, and lowered the ${R}_0$ to 1.78. We showed that an early evacuation of all passengers on 3 February would have been associated with 76 infected persons in their incubation time.The cruise ship conditions clearly amplified an already highly transmissible disease. The public health measures prevented more than 2000 additional cases compared to no interventions. However, evacuating all passengers and crew early on in the outbreak would have prevented many more passengers and crew from infection.",2020,"Rocklöv, J.; Sjödin, H.; Wilder-Smith, A.",Journal of Travel Medicine,3006304371,#2926,True
e9239100c5493ea914dc23c3d7a262f4326022ac,CZI,Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection,10.1128/mBio.02764-19,,,cc-by,"Coronaviruses (CoVs) are common human and animal pathogens that can transmit zoonotically and cause severe respiratory disease syndromes. CoV infection requires spike proteins, which bind viruses to host cell receptors and catalyze virus-cell membrane fusion. Several CoV strains have spike proteins with two receptor-binding domains, an S1A that engages host sialic acids and an S1B that recognizes host transmembrane proteins. As this bivalent binding may enable broad zoonotic CoV infection, we aimed to identify roles for each receptor in distinct infection stages. Focusing on two betacoronaviruses, murine JHM-CoV and human Middle East respiratory syndrome coronavirus (MERS-CoV), we found that virus particle binding to cells was mediated by sialic acids; however, the transmembrane protein receptors were required for a subsequent virus infection. These results favored a two-step process in which viruses first adhere to sialic acids and then require subsequent engagement with protein receptors during infectious cell entry. However, sialic acids sufficiently facilitated the later stages of virus spread through cell-cell membrane fusion, without requiring protein receptors. This virus spread in the absence of the prototype protein receptors was increased by adaptive S1A mutations. Overall, these findings reveal roles for sialic acids in virus-cell binding, viral spike protein-directed cell-cell fusion, and resultant spread of CoV infections.IMPORTANCE CoVs can transmit from animals to humans to cause serious disease. This zoonotic transmission uses spike proteins, which bind CoVs to cells with two receptor-binding domains. Here, we identified the roles for the two binding processes in the CoV infection process. Binding to sialic acids promoted infection and also supported the intercellular expansion of CoV infections through syncytial development. Adaptive mutations in the sialic acid-binding spike domains increased the intercellular expansion process. These findings raise the possibility that the lectin-like properties of many CoVs contribute to facile zoonotic transmission and intercellular spread within infected organisms.",2020,"Qing, Enya; Hantak, Michael; Perlman, Stanley; Gallagher, Tom",mBio,3005811007,#2427,True
469ed0f00c09e2637351c9735c306f27acf3aace,CZI,First two months of the 2019 Coronavirus Disease (COVID-19) epidemic in China: real-time surveillance and evaluation with a second derivative model,10.1186/s41256-020-00137-4,,,cc-by,"Similar to outbreaks of many other infectious diseases, success in controlling the novel 2019 coronavirus infection requires a timely and accurate monitoring of the epidemic, particularly during its early period with rather limited data while the need for information increases explosively.",2020,"Chen, Xinguang; Yu, Bin",Global Health Research and Policy,3006645647,#5595,True
4e550e034ccca6fa2a91e481ddba24db67bc9ae5,CZI,Effectiveness of airport screening at detecting travellers infected with novel coronavirus (2019-nCoV),10.2807/1560-7917.ES.2020.25.5.2000080,,,cc-by,"We simulated 100 2019-nCoV infected travellers planning to board a flight who would pose a risk for seeding transmission in a new region. The duration of travel was considered as the flight time plus a small amount of additional travel time (ca 1 hour) for airport procedures. We assumed that infected individuals will develop symptoms, including fever, at the end of their incubation period (mean 5.2 days (Table)) [8] and progress to more severe symptoms after a few days, resulting in hospitalisation and isolation. We also took into account that individuals may have asymptomatic (subclinical) infection that would not be detected by thermal scanning or cause them to seek medical care, although these individuals may be infectious, and that infected travellers may exhibit severe symptoms during their travel and be hospitalised upon arrival without undergoing entry screening. We then estimated the proportion of infected travellers who would be detected by exit and entry screening, develop severe symptoms during travel, or go undetected, under varying assumptions of: (i) the duration of travel; (ii) the sensitivity of exit and entry screening; (iii) the proportion of asymptomatic infections; (iv) the incubation period and (v) the time from symptom onset to hospitalisation (Table).",2020,"Quilty, Billy J; Clifford, Sam; group2, CMMID nCoV working; Flasche, Stefan; Eggo, Rosalind M",Eurosurveillance,3005151538,#682,True
4bbb0c59babc718f67953fae032dad6ae0d7aeb1,CZI,Genome Detective Coronavirus Typing Tool for rapid identification and characterization of novel coronavirus genomes,10.1093/bioinformatics/btaa145,,32108862,cc-by-nc,"SUMMARY: Genome Detective is a web-based, user-friendly software application to quickly and accurately assemble all known virus genomes from next generation sequencing datasets. This application allows the identification of phylogenetic clusters and genotypes from assembled genomes in FASTA format. Since its release in 2019, we have produced a number of typing tools for emergent viruses that have caused large outbreaks, such as Zika and Yellow Fever Virus in Brazil. Here, we present The Genome Detective Coronavirus Typing Tool that can accurately identify the novel severe acute respiratory syndrome (SARS) related coronavirus (SARS-CoV-2) sequences isolated in China and around the world. The tool can accept up to 2,000 sequences per submission and the analysis of a new whole genome sequence will take approximately one minute. The tool has been tested and validated with hundreds of whole genomes from ten coronavirus species, and correctly classified all of the SARS-related coronavirus (SARSr-CoV) and all of the available public data for SARS-CoV-2. The tool also allows tracking of new viral mutations as the outbreak expands globally, which may help to accelerate the development of novel diagnostics, drugs and vaccines to stop the COVID-19 disease. AVAILABILITY: https://www.genomedetective.com/app/typingtool/cov. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.",2020,"Cleemput, S.; Dumon, W.; Fonseca, V.; Karim, W. A.; Giovanetti, M.; Alcantara, L. C.; Deforche, K.; de Oliveira, T.","Bioinformatics (Oxford, England)",3003548522,#2776,True
c821803c55c6aad89b6d0c1d3ba252051e464017,CZI,Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Pneumonia Monitored by Quantitative RT-PCR,10.3346/jkms.2020.35.e79,,,cc-by-nc,"Since mid-December of 2019, coronavirus disease 2019 (COVID-19) has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, beta-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.",2020,"Lim, Jaegyun; Jeon, Seunghyun; Shin, Hyun-Young; Kim, Moon Jung; Seong, Yu Min; Lee, Wang Jun; Choe, Kang-Won; Kang, Yu Min; Lee, Baeckseung; Park, Sang-Joon",Journal of Korean Medical Science,3005657121,#3770,True
c3bee2a4caca614b34f92c17b643b854dcdab28d,CZI,Emergence of Novel Coronavirus 2019-nCoV: Need for Rapid Vaccine and Biologics Development,10.3390/pathogens9020148,,,cc-by,"Novel Coronavirus (2019-nCoV) is an emerging pathogen that was first identified in Wuhan, China in late December 2019. This virus is responsible for the ongoing outbreak that causes severe respiratory illness and pneumonia-like infection in humans. Due to the increasing number of cases in China and outside China, the WHO declared coronavirus as a global health emergency. Nearly 35,000 cases were reported and at least 24 other countries or territories have reported coronavirus cases as early on as February. Inter-human transmission was reported in a few countries, including the United States. Neither an effective anti-viral nor a vaccine is currently available to treat this infection. As the virus is a newly emerging pathogen, many questions remain unanswered regarding the virus’s reservoirs, pathogenesis, transmissibility, and much more is unknown. The collaborative efforts of researchers are needed to fill the knowledge gaps about this new virus, to develop the proper diagnostic tools, and effective treatment to combat this infection. Recent advancements in plant biotechnology proved that plants have the ability to produce vaccines or biopharmaceuticals rapidly in a short time. In this review, the outbreak of 2019-nCoV in China, the need for rapid vaccine development, and the potential of a plant system for biopharmaceutical development are discussed.",2020,"Shanmugaraj, Balamurugan; Malla, Ashwini; Phoolcharoen, Waranyoo",Pathogens,3003886061,#1502,True
715842fa536064980818ad7e31ce511272a4b6bc,CZI,The coronavirus 2019-nCoV epidemic: Is hindsight 20/20?,10.1016/j.eclinm.2020.100289,,,cc-by-nc-nd,,2020,"Malta, Monica; Rimoin, Anne W.; Strathdee, Steffanie A.",EClinicalMedicine,3004912618,#3333,True
601d3c7ae4ebcd2d835e9cf8d7427ebd0b5db83f,CZI,Nonstructural proteins NS7b and NS8 are likely to be phylogenetically associated with evolution of 2019-nCoV,10.1016/j.meegid.2020.104272,,,cc-by-nc-nd,"The seventh novel human infecting Betacoronavirus that causes pneumonia (2019 novel coronavirus, 2019-nCoV) originated in Wuhan, China. The evolutionary relationship between 2019-nCoV and the other human respiratory illness-causing coronavirus is not closely related. We sought to characterize the relationship of the translated proteins of 2019-nCoV with other species of Orthocoronavirinae. A phylogenetic tree was constructed from the genome sequences. A cluster tree was developed from the profiles retrieved from the presence and absence of homologs of ten 2019-nCoV proteins. The combined data were used to characterize the relationship of the translated proteins of 2019-nCoV to other species of Orthocoronavirinae. Our analysis reliably suggests that 2019-nCoV is most closely related to BatCoV RaTG13 and belongs to subgenus Sarbecovirus of Betacoronavirus, together with SARS coronavirus and Bat-SARS-like coronavirus. The phylogenetic profiling cluster of homolog proteins of one annotated 2019-nCoV protein against other genome sequences revealed two clades of ten 2019-nCoV proteins. Clade 1 consisted of a group of conserved proteins in Orthocoronavirinae comprising Orf1ab polyprotein, Nucleocapsid protein, Spike glycoprotein, and Membrane protein. Clade 2 comprised six proteins exclusive to Sarbecovirus and Hibecovirus. Two of six Clade 2 nonstructural proteins, NS7b and NS8, were exclusively conserved among 2019-nCoV, BetaCoV_RaTG, and BatSARS-like Cov. NS7b and NS8 have previously been shown to affect immune response signaling in the SARS-CoV experimental model. Thus, we speculated that knowledge of the functional changes in the NS7b and NS8 proteins during evolution may provide important information to explore the human infective property of 2019-nCoV.",2020,"Fahmi, Muhamad; Kubota, Yukihiko; Ito, Masahiro","Infection, Genetics and Evolution",2286137332,#4581,True
06c89f69aa7b5f9648d2c1543b8246fe9c3610cf,CZI,Pathogenicity and Transmissibility of 2019-nCoV—A Quick Overview and Comparison with Other Emerging Viruses,10.1016/j.micinf.2020.01.004,,,cc-by-nc-nd,"A zoonotic coronavirus, labeled as 2019-nCoV by The World Health Organization (WHO), has been identified as the causative agent of the viral pneumonia outbreak in Wuhan, China, at the end of 2019. Although 2019-nCoV can cause a severe respiratory illness like SARS and MERS, evidence from clinics suggested that 2019-nCoV is generally less pathogenic than SARS-CoV, and much less than MERS-CoV. The transmissibility of 2019-nCoV is still debated and needs to be further assessed. To avoid the 2019-nCoV outbreak turning into an epidemic or even a pandemic and to minimize the mortality rate, China activated emergency response procedures, but much remains to be learned about the features of the virus to refine the risk assessment and response. Here, the current knowledge in 2019-nCoV pathogenicity and transmissibility is summarized in comparison with several commonly known emerging viruses, and information urgently needed for a better control of the disease is highlighted.",2020,"Chen, Jieliang",Microbes and Infection,,#236,True
acb678bdd7634055de18d0b89bb6a4890e6a0306,CZI,Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro,10.1038/s41422-020-0282-0,,,cc-by,,2020,"Wang, Manli; Cao, Ruiyuan; Zhang, Leike; Yang, Xinglou; Liu, Jia; Xu, Mingyue; Shi, Zhengli; Hu, Zhihong; Zhong, Wu; Xiao, Gengfu",Cell Research,3005212621,#205,True
47772f3e98d8c61bb9782531a0338ba85f27bf3f,CZI,Potential for global spread of a novel coronavirus from China,10.1093/jtm/taaa011,,,cc-by-nc,,2020,"Bogoch, I. I.; Watts, A.; Thomas-Bachli, A.; Huber, C.; Kraemer, M. U. G.; Khan, K.",Journal of travel medicine,3004047749,#102,True
544a170a18bae9bf44c531c2b0b4bdc5e85ea8f5,CZI,Severe acute respiratory symptoms and suspected sars again 2020,10.12809/hkmj208375,,,cc-by-nc-nd,,2020,"Hon, K. L.; Leung, K. K. Y.",Hong Kong Medical Journal,2029408250,#3395,True
4ff89a71126d2932544a8337ba28787fde5f02a8,CZI,Statistics-Based Predictions of Coronavirus Epidemic Spreading in Mainland China,10.20535/ibb.2020.4.1.195074,,,cc-by,"Information about the open-access article 'Statistics-Based Predictions of Coronavirus Epidemic Spreading in Mainland China' in DOAJ. DOAJ is an online directory that indexes and provides access to quality open access, peer-reviewed journals.",2020,"Nesteruk, Igor",Innovative Biosystems and Bioengineering,3006304781,#1218,True
ac37ba61c91bb6939a507dbf4efe2119ddafeb9c,CZI,"Early transmission patterns of coronavirus disease 2019 (COVID-19) in travellers from Wuhan to Thailand, January 2020",10.2807/1560-7917.ES.2020.25.8.2000097,,,cc-by,,2020,"Okada, Pilailuk; Buathong, Rome; Phuygun, Siripaporn; Thanadachakul, Thanutsapa; Parnmen, Sittiporn; Wongboot, Warawan; Waicharoen, Sunthareeya; Wacharapluesadee, Supaporn; Uttayamakul, Sumonmal; Vachiraphan, Apichart; Chittaganpitch, Malinee; Mekha, Nanthawan; Janejai, Noppavan; Iamsirithaworn, Sopon; Lee, Raphael TC; Maurer-Stroh, Sebastian",Eurosurveillance,3005657121,#2582,True
6dfe2e77c8175b3eb38d6fc3ccc440fb81a0e2f0,CZI,HRCT Imaging Features in Representative Imported Cases of 2019 Novel Coronavirus Pneumonia,10.1093/pcmedi/pbaa004,,,cc-by-nc,"With the spread of novel coronavirus (2019-nCoV) pneumonia, chest high-resolution computed tomography (HRCT) has been one of the key diagnostic tools. To achieve early and accurate diagnostics, determining the radiological characteristics of the disease is of great importance. In this small scale research we retrospectively reviewed and selected six cases confirmed with 2019-nCoV infection in West China Hospital and investigated their initial and follow-up HRCT features, along with the clinical characteristics. The 2019-nCoV pneumonia basically showed a multifocal or unifocal involvement of ground-glass opacity (GGO), sometimes with consolidation and fibrosis. No pleural effusion or lymphadenopathy was identified in our presented cased. The follow-up CT generally demonstrated mild to moderate progression of the lesion, with only one case showing remission by the reducing extent and density of the airspace opacification.",2020,"Diao, Kaiyue; Han, Peilun; Pang, Tong; Li, Yuan; Yang, Zhigang",Precision Clinical Medicine,3006467527,#781,True
c9fee561c2a3834645dbb61dc4ae6448051da492,CZI,Comprehensive Genomic Characterization Analysis of lncRNAs in Cells With Porcine Delta Coronavirus Infection,10.3389/fmicb.2019.03036,,,cc-by,"Porcine delta coronavirus (PDCoV) is a novel emerging enterocytetropic virus causing diarrhea, vomiting, dehydration, and mortality in suckling piglets. Long non-coding RNAs (lncRNAs) are known to be important regulators during virus infection. Here, we describe a comprehensive transcriptome profile of lncRNA in PDCoV-infected swine testicular (ST) cells. In total, 1,308 annotated and 1,190 novel lncRNA candidate sequences were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these lncRNAs might be involved in numerous biological processes. Clustering analysis of differentially expressed lncRNAs showed that 454 annotated and 376 novel lncRNAs were regulated after PDCoV infection. Furthermore, we constructed a lncRNA-protein-coding gene co-expression interaction network. The KEGG analysis of the co-expressed genes showed that these differentially expressed lncRNAs were enriched in pathways related to metabolism and TNF signaling. Our study provided comprehensive information about lncRNAs that would be a useful resource for studying the pathogenesis of and designing antiviral therapy for PDCoV infection.",2020,"Liui, Junli; Wang, Fangfang; Du, Liuyang; Li, Juan; Yu, Tianqi; Jin, Yulan; Yan, Yan; Zhou, Jiyong; Gu, Jinyan",Frontiers in Microbiology,3003967510,#5462,True
655537fc8cc52bccf43cf7189ab060d3097caa7a,CZI,Potential Factors Influencing Repeated SARS Outbreaks in China,10.3390/ijerph17051633,,,cc-by,"Within last 17 years two widespread epidemics of severe acute respiratory syndrome (SARS) occurred in China, which were caused by related coronaviruses (CoVs): SARS-CoV and SARS-CoV-2. Although the origin(s) of these viruses are still unknown and their occurrences in nature are mysterious, some general patterns of their pathogenesis and epidemics are noticeable. Both viruses utilize the same receptor—angiotensin-converting enzyme 2 (ACE2)—for invading human bodies. Both epidemics occurred in cold dry winter seasons celebrated with major holidays, and started in regions where dietary consumption of wildlife is a fashion. Thus, if bats were the natural hosts of SARS-CoVs, cold temperature and low humidity in these times might provide conducive environmental conditions for prolonged viral survival in these regions concentrated with bats. The widespread existence of these bat-carried or -released viruses might have an easier time in breaking through human defenses when harsh winter makes human bodies more vulnerable. Once succeeding in making some initial human infections, spreading of the disease was made convenient with increased social gathering and holiday travel. These natural and social factors influenced the general progression and trajectory of the SARS epidemiology. However, some unique factors might also contribute to the origination of SARS in Wuhan. These factors are discussed in different scenarios in order to promote more research for achieving final validation.",2020,"Sun, Zhong; Thilakavathy, Karuppiah; Kumar, S. S.; He, Guozhong; Liu, V. Shi",International Journal of Environmental Research and Public Health,2615948593,#3296,True
bb7cd48a85b72f8d73e57d655c6d8a034fce3778,CZI,Puzzle of highly pathogenic human coronaviruses (2019-nCoV),10.1007/s13238-020-00693-y,,32088858,cc-by,,2020,"Li, Jing; Liu, Wenjun",Protein Cell,2766462213,#1815,True
3c42431c5b95e707486ce7441ac139071e07b706,CZI,RETRACTION: Retraction-Chinese medical staff request international medical assistance in fighting against COVID-19,10.1016/s2214-109x(20)30076-0,,32113504,cc-by,,2020,"The Editors Of The Lancet Global, Health",The Lancet. Global health,2794878804,#5486,False
6a93283b499ae5bc6aaf29f14e701dc8f25138ea,CZI,"Critical care response to a hospital outbreak of the 2019-nCoV infection in Shenzhen, China",10.1186/s13054-020-2786-x,,,cc-by,,2020,"Liu, Yong; Li, Jinxiu; Feng, Yongwen",Critical Care,2537200785,#1225,True
6fc52ed878c271020a2a375bb6e4b12943a7666c,CZI,Effectiveness for the Response to COVID-19: The MERS Outbreak Containment Procedures,10.24171/j.phrp.2020.11.1.01,,,cc-by-nc-nd,"In the current issue of Osong Public Health and Research Perspectives, 3 studies are presented dealing with COVID-19. A study by Kim et al, analyzed the genetic information of the COVID-19 virus isolated from a patient in South Korea. The virus was identified by real-time reverse transcriptase (RT) PCR followed by Next Generation Sequencing of the full-length of the genome [5]. In an interim report by the COVID-19 National Emergency Response Center of the KCDC, epidemiological and clinical characteristics of COVID-19 in 28 cases in South Korea were reported. There were 53.9% of cases who were males, with 16 cases in patients who had traveled abroad, of which 11 cases (39.3%) were from Wuhan, China, and 12 of the remaining cases were believed to have been infected in South Korea. The incubation period was 4.8 days. Most secondary infected cases were from family members outside the family home (66.7%) and within the family home (75%) [6].",2020,"Cho, Hae-Wol",Osong Public Health and Research Perspectives,3005887838,#2662,False
1d7f8850c5244fdc9b387038e7eeae9bcbbde6d2,CZI,Optimization Method for Forecasting Confirmed Cases of COVID-19 in China,10.3390/jcm9030674,,32131537,cc-by,"In December 2019, a novel coronavirus, called COVID-19, was discovered in Wuhan, China, and has spread to different cities in China as well as to 24 other countries. The number of confirmed cases is increasing daily and reached 34,598 on 8 February 2020. In the current study, we present a new forecasting model to estimate and forecast the number of confirmed cases of COVID-19 in the upcoming ten days based on the previously confirmed cases recorded in China. The proposed model is an improved adaptive neuro-fuzzy inference system (ANFIS) using an enhanced flower pollination algorithm (FPA) by using the salp swarm algorithm (SSA). In general, SSA is employed to improve FPA to avoid its drawbacks (i.e., getting trapped at the local optima). The main idea of the proposed model, called FPASSA-ANFIS, is to improve the performance of ANFIS by determining the parameters of ANFIS using FPASSA. The FPASSA-ANFIS model is evaluated using the World Health Organization (WHO) official data of the outbreak of the COVID-19 to forecast the confirmed cases of the upcoming ten days. More so, the FPASSA-ANFIS model is compared to several existing models, and it showed better performance in terms of Mean Absolute Percentage Error (MAPE), Root Mean Squared Relative Error (RMSRE), Root Mean Squared Relative Error (RMSRE), coefficient of determination ( R 2 ), and computing time. Furthermore, we tested the proposed model using two different datasets of weekly influenza confirmed cases in two countries, namely the USA and China. The outcomes also showed good performances.",2020,"Al-Qaness, Mohammed A. A.; Ewees, Ahmed A.; Fan, Hong; Abd El Aziz, Mohamed",J Clin Med,3006671704,#4638,True
f294f0df7468a8ac9e27776cc15fa20297a9f040,CZI,Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV,10.3390/v12020244,,,cc-by,"After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as “coronavirus disease 2019” (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.",2020,"Xu, Jiabao; Zhao, Shizhe; Teng, Tieshan; Abdalla, Abualgasim Elgaili; Zhu, Wan; Xie, Longxiang; Wang, Yunlong; Guo, Xiangqian",Viruses,2163319355,#1449,True
60e51d3d13b027492b9f3b8693c58dd8b5385ada,CZI,"Novel coronavirus infection during the 2019–2020 epidemic: preparing intensive care units—the experience in Sichuan Province, China",10.1007/s00134-020-05954-2,,,cc-by-nc,"Novel coronavirus infection special intensive care team We set up a special emergency multi-disciplinary intensive care team to discuss the problems that we might encounter and countermeasures. Team members include intensive care unit (ICU) physician, infectious disease physician, nurse, respiratory therapist, nosocomial infection control expert, and administrative staff. We first evaluated the isolation conditions and the capacity of our department to admit a larger number of patients. Second, we specified the protection levels for different types of health care activities. Third, we assigned special work such as patient screening, consultation, and transfer to designated staff to minimize the number of health workers who had contact with patients with nCoV infection.ID - LiaoER -",2020,"Liao, Xuelian; Wang, Bo; Kang, Yan",Intensive Care Medicine,,#305,True
253cfd411f93ef88f702accd0fa195f24d1d2925,CZI,Return of the Coronavirus: 2019-nCoV,10.3390/v12020135,,,cc-by,"The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the most recent emergent group 2B coronavirus.",2020,"Gralinski, E. Lisa; Menachery, D. Vineet",Viruses,3002812395,#61,True
e7fbca71f16c3fbb78d754c95f24f58afc944c68,CZI,Application of the ARIMA model on the COVID-2019 epidemic dataset,10.1016/j.dib.2020.105340,,,cc-by-nc-nd,"Coronavirus disease 2019 (COVID-2019) has been recognized as a global threat, and several studies are being conducted using various mathematical models to predict the probable evolution of this epidemic. These mathematical models based on various factors and analyses are subject to potential bias. Here, we propose a simple econometric model that could be useful to predict the spread of COVID-2019. We performed Auto Regressive Integrated Moving Average (ARIMA) model prediction on the Johns Hopkins epidemiological data to predict the epidemiological trend of the prevalence and incidence of COVID-2019. For further comparison or for future perspective, case definition and data collection have to be maintained in real time.",2020,"Benvenuto, Domenico; Giovanetti, Marta; Vassallo, Lazzaro; Angeletti, Silvia; Ciccozzi, Massimo",Data in Brief,3002991745,#2363,True
c200af0e42a9aa8539b208d993015a75a2fe1151,CZI,Passengers' destinations from China: low risk of Novel Coronavirus (2019-nCoV) transmission into Africa and South America,10.1017/S0950268820000424,,32100667,cc-by,"Novel Coronavirus (2019-nCoV [SARS-COV-2]) was detected in humans during the last week of December 2019 at Wuhan city in China, and caused 24 554 cases in 27 countries and territories as of 5 February 2020. The objective of this study was to estimate the risk of transmission of 2019-nCoV through human passenger air flight from four major cities of China (Wuhan, Beijing, Shanghai and Guangzhou) to the passengers' destination countries. We extracted the weekly simulated passengers' end destination data for the period of 1-31 January 2020 from FLIRT, an online air travel dataset that uses information from 800 airlines to show the direct flight and passengers' end destination. We estimated a risk index of 2019-nCoV transmission based on the number of travellers to destination countries, weighted by the number of confirmed cases of the departed city reported by the World Health Organization (WHO). We ranked each country based on the risk index in four quantiles (4th quantile being the highest risk and 1st quantile being the lowest risk). During the period, 388 287 passengers were destined for 1297 airports in 168 countries or territories across the world. The risk index of 2019-nCoV among the countries had a very high correlation with the WHO-reported confirmed cases (0.97). According to our risk score classification, of the countries that reported at least one Coronavirus-infected pneumonia (COVID-19) case as of 5 February 2020, 24 countries were in the 4th quantile of the risk index, two in the 3rd quantile, one in the 2nd quantile and none in the 1st quantile. Outside China, countries with a higher risk of 2019-nCoV transmission are Thailand, Cambodia, Malaysia, Canada and the USA, all of which reported at least one case. In pan-Europe, UK, France, Russia, Germany and Italy; in North America, USA and Canada; in Oceania, Australia had high risk, all of them reported at least one case. In Africa and South America, the risk of transmission is very low with Ethiopia, South Africa, Egypt, Mauritius and Brazil showing a similar risk of transmission compared to the risk of any of the countries where at least one case is detected. The risk of transmission on 31 January 2020 was very high in neighbouring Asian countries, followed by Europe (UK, France, Russia and Germany), Oceania (Australia) and North America (USA and Canada). Increased public health response including early case recognition, isolation of identified case, contract tracing and targeted airport screening, public awareness and vigilance of health workers will help mitigate the force of further spread to naïve countries.",2020,"Haider, Najmul; Yavlinsky, Alexei; Simons, David; Osman, Abdinasir Yusuf; Ntoumi, Francine; Zumla, Alimuddin; Kock, Richard",Epidemiol Infect,3006028839,#2270,True
5734e3b81e16fe1976a129c5a0872716f3dd50b8,CZI,A new coronavirus associated with human respiratory disease in China,10.1038/s41586-020-2008-3,,32015508,cc-by,"Emerging infectious diseases, such as SARS and Zika, present a major threat to public health(1-3). Despite intense research efforts, how, when and where new diseases appear are still the source of considerable uncertainly. A severe respiratory disease was recently reported in the city Wuhan, Hubei province, China. Up to 25th of January 2020, at least 1,975 cases have been reported since the first patient was hospitalized on the 12th of December 2019. Epidemiological investigation suggested that the outbreak was associated with a seafood market in Wuhan. We studied one patient who was a worker at the market, and who was admitted to Wuhan Central Hospital on 26th of December 2019 experiencing a severe respiratory syndrome including fever, dizziness and cough. Metagenomic RNA sequencing(4) of a bronchoalveolar lavage fluid sample identified a novel RNA virus from the family Coronaviridae, designed here as WH-Human-1 coronavirus. Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) previously sampled from bats in China. This outbreak highlights the ongoing capacity of viral spill-over from animals to cause severe disease in humans.",2020,"Wu, Fan; Zhao, Su; Yu, Bin; Chen, Yan-Mei; Wang, Wen; Song, Zhi-Gang; Hu, Yi; Tao, Zhao-Wu; Tian, Jun-Hua; Pei, Yuan-Yuan; Yuan, Ming-Li; Zhang, Yu-Ling; Dai, Fa-Hui; Liu, Yi; Wang, Qi-Min; Zheng, Jiao-Jiao; Xu, Lin; Holmes, Edward C.; Zhang, Yong-Zhen",Nature,3003217347,#258,True
c2302facc633f9dfaf8597ffe57ca929e5d08b78,CZI,Moral imperative for the immediate release of 2019-nCoV sequence data,10.1093/nsr/nwaa030,,,cc-by,,2020,"Wu, Chung- I.; Poo, Mu-ming",National Science Review,2805337112,#1185,True
8819d114fe2dd2335a0545d53fea17deb6aa3943,CZI,Technical guidance for laboratory testing of 2019-nCoV infection (third edition),10.1016/j.bsheal.2020.02.001,,,cc-by-nc-nd,,2020,,Biosafety and Health,2992772421,#351,False
417cbe38a2f8a93d0827cd67f4c42076921d6050,CZI,Discovery and development of safe-in-man broad-spectrum antiviral agents,10.1016/j.ijid.2020.02.018,,,cc-by-nc-nd,"Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 119 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.",2020,"Andersen, Petter I.; Ianevski, Aleksandr; Lysvand, Hilde; Vitkauskiene, Astra; Oksenych, Valentyn; Bjørås, Magnar; Telling, Kaidi; Lutsar, Irja; Dampis, Uga; Irie, Yasuhiko; Tenson, Tanel; Kantele, Anu; Kainov, Denis E.",International Journal of Infectious Diseases,2980655992,#1172,True
2892aee133b8b4037ace7ec6dfe6cab17e466292,CZI,"Li Wenliang, a face to the frontline healthcare worker? The first doctor to notify the emergence of the SARS-CoV-2, (COVID-19), outbreak",10.1016/j.ijid.2020.02.052,,,cc-by-nc-nd,,2020,"Petersen, Eskild; Hui, David; Hamer, Davidson H.; Blumberg, Lucille; Madoff, Lawrence C.; Pollack, Marjorie; Lee, Shui Shan; McLellan, Susan; Memish, Ziad; Praharaj, Ira; Wasserman, Sean; Ntoumi, Francine; Azhar, Esam Ibraheem; McHugh, Timothy D.; Kock, Richard; Ippolito, Guiseppe; Zumla, Ali; Koopmans, Marion",International Journal of Infectious Diseases,2600370084,#4474,True
6abb30ae61aa5e41f16a28b9437940d5d76d745b,CZI,"Phase-adjusted estimation of the number of Coronavirus Disease 2019 cases in Wuhan, China",10.1038/s41421-020-0148-0,,,cc-by,"An outbreak of clusters of viral pneumonia due to a novel coronavirus (2019-nCoV/SARS-CoV-2) happened in Wuhan, Hubei Province in China in December 2019. Since the outbreak, several groups reported estimated R0 of Coronavirus Disease 2019 (COVID-19) and generated valuable prediction for the early phase of this outbreak. After implementation of strict prevention and control measures in China, new estimation is needed. An infectious disease dynamics SEIR (Susceptible, Exposed, Infectious, and Removed) model was applied to estimate the epidemic trend in Wuhan, China under two assumptions of Rt. In the first assumption, Rt was assumed to maintain over 1. The estimated number of infections would continue to increase throughout February without any indication of dropping with Rt = 1.9, 2.6, or 3.1. The number of infections would reach 11,044, 70,258, and 227,989, respectively, by 29 February 2020. In the second assumption, Rt was assumed to gradually decrease at different phases from high level of transmission (Rt = 3.1, 2.6, and 1.9) to below 1 (Rt = 0.9 or 0.5) owing to increasingly implemented public health intervention. Several phases were divided by the dates when various levels of prevention and control measures were taken in effect in Wuhan. The estimated number of infections would reach the peak in late February, which is 58,077–84,520 or 55,869–81,393. Whether or not the peak of the number of infections would occur in February 2020 may be an important index for evaluating the sufficiency of the current measures taken in China. Regardless of the occurrence of the peak, the currently strict measures in Wuhan should be continuously implemented and necessary strict public health measures should be applied in other locations in China with high number of COVID-19 cases, in order to reduce Rt to an ideal level and control the infection.",2020,"Wang, Huwen; Wang, Zezhou; Dong, Yinqiao; Chang, Ruijie; Xu, Chen; Yu, Xiaoyue; Zhang, Shuxian; Tsamlag, Lhakpa; Shang, Meili; Huang, Jinyan; Wang, Ying; Xu, Gang; Shen, Tian; Zhang, Xinxin; Cai, Yong",Cell Discovery,3004397688,#1750,True
6d16e166279a7d116a78a21d4bd4c00b505a617e,CZI,The reproductive number of COVID-19 is higher compared to SARS coronavirus,10.1093/jtm/taaa021,,,cc-by-nc,"Teaser: Our review found the average R0 for 2019-nCoV to be 3.28, which exceeds WHO estimates of 1.4 to 2.5.Here we review the basic reproduction number (R0) of the 2019-nCoV virus. R0 is an indication of the transmissibility of a virus, representing the average number of new infections generated by an infectious person in a totally naïve population. For R0 greater than one the number infected is likely to increase, and for R0 less than one transmission is likely to die out. The basic reproduction number is a central concept in infectious disease epidemiology, indicating the risk of an infectious agent with respect to epidemic spread.",2020,"Liu, Ying; Gayle, Albert A.; Wilder-Smith, Annelies; Rocklöv, Joacim",Journal of Travel Medicine,3006642361,#852,True
5423004ce74c612a32c8ff24b3f161eb92a62979,CZI,"Middle East respiratory syndrome coronavirus (MERS-CoV) neutralising antibodies in a high-risk human population, Morocco, November 2017 to January 2018",10.2807/1560-7917.ES.2019.24.48.1900244,,,cc-by,,2019,"Abbad, Anass; Perera, Ranawaka APM; Anga, Latifa; Faouzi, Abdellah; Minh, Nhu Nguyen Tran; Malik, Sk Md Mamunur Rahman; Iounes, Nadia; Maaroufi, Abderrahmane; Kerkhove, Maria D Van; Peiris, Malik; Nourlil, Jalal",Eurosurveillance,2991640369,#3502,True
779c1b5cb3afe3d50219aa2af791014a22eb355a,CZI,"Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections",10.3390/v12020194,,,cc-by,"In early December 2019 a cluster of cases of pneumonia of unknown cause was identified in Wuhan, a city of 11 million persons in the People’s Republic of China. Further investigation revealed these cases to result from infection with a newly identified coronavirus, termed the 2019-nCoV. The infection moved rapidly through China, spread to Thailand and Japan, extended into adjacent countries through infected persons travelling by air, eventually reaching multiple countries and continents. Similar to such other coronaviruses as those causing the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), the new coronavirus was reported to spread via natural aerosols from human-to-human. In the early stages of this epidemic the case fatality rate is estimated to be approximately 2%, with the majority of deaths occurring in special populations. Unfortunately, there is limited experience with coronavirus infections during pregnancy, and it now appears certain that pregnant women have become infected during the present 2019-nCoV epidemic. In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. Recommendations are also made for the consideration of pregnant women in the design, clinical trials, and implementation of future 2019-nCoV vaccines.",2020,"Schwartz, David A.; Graham, Ashley L.",Viruses,3004581842,#590,True
355f8c97211726732a20ce50da8b11ffdf3303ab,CZI,"Laboratory readiness and response for novel coronavirus (2019-nCoV) in expert laboratories in 30 EU/EEA countries, January 2020",10.2807/1560-7917.ES.2020.25.6.2000082,,,cc-by,"Timely detection of novel coronavirus (2019-nCoV) infection cases is crucial to interrupt the spread of this virus. We assessed the required expertise and capacity for molecular detection of 2019-nCoV in specialised laboratories in 30 European Union/European Economic Area (EU/EEA) countries. Thirty-eight laboratories in 24 EU/EEA countries had diagnostic tests available by 29 January 2020. A coverage of all EU/EEA countries was expected by mid-February. Availability of primers/probes, positive controls and personnel were main implementation barriers.",2020,"Reusken, Chantal B.E.M.; Broberg, Eeva K.; Haagmans, Bart; Meijer, Adam; Corman, Victor M.; Papa, Anna; Charrel, Remi; Drosten, Christian; Koopmans, Marion; Leitmeyer, Katrin",Eurosurveillance,3006255311,#664,False
cb0831902de1f8a19992ff86bcc7e15fa2d7d687,CZI,"Initial Cluster of Novel Coronavirus (2019-nCoV) Infections in Wuhan, China Is Consistent with Substantial Human-to-Human Transmission",10.3390/jcm9020488,,32054045,cc-by,"Reanalysis of the epidemic curve from the initial cluster of cases with novel coronavirus (2019-nCoV) in December 2019 indicates substantial human-to-human transmission. It is possible that the common exposure history at a seafood market in Wuhan originated from the human-to-human transmission events within the market, and the early, strong emphasis that market exposure indicated animal-to-human transmission was potentially the result of observer bias. To support the hypothesis of zoonotic origin of 2019-nCoV stemming from the Huanan seafood market, the index case should have had exposure history related to the market and the virus should have been identified from animals sold at the market. As these requirements remain unmet, zoonotic spillover at the market must not be overemphasized.",2020,"Nishiura, Hiroshi; Linton, Natalie M.; Akhmetzhanov, Andrei R.",J Clin Med,3005599914,#933,True
cef8a948bad454c49e10e6aed8c0cb2ce3215c62,CZI,Potential association between COVID-19 mortality and health-care resource availability,10.1016/S2214-109X(20)30068-1,,,cc-by-nc-nd,"As recorded by the Chinese Center for Disease Control and Prevention (China CDC), by Feb 16, 2020, there had been 70 641 confirmed cases and 1772 deaths due to COVID-19, with an average mortality of about 2·5%. However, in-depth analysis of these data show clear disparities in mortality rates between Wuhan (>3%), different regions of Hubei (about 2·9% on average), and across the other provinces of China (about 0·7% on average). We postulate that this is likely to be related to the rapid escalation in the number of infections around the epicentre of the outbreak, which has resulted in an insufficiency of health-care resources, thereby negatively affecting patient outcomes in Hubei, while this has not yet been the situation for the other parts of China (figure A, B). If we assume that average levels of health care are similar throughout China, higher numbers of infections in a given population can be considered an indirect indicator of a heavier health-care burden. Plotting mortality against the incidence of COVID-19 (cumulative number of confirmed cases since the start of the outbreak, per 10 000 population) showed a significant positive correlation (figure C), suggesting that mortality is correlated with health-care burden.",,"Ji, Yunpeng; Ma, Zhongren; Peppelenbosch, Maikel P.; Pan, Qiuwei",The Lancet Global Health,2343822881,#1979,False
4af62711ee4cca0c90baf73be3e83ea95e68c045,CZI,Estimation of the reproductive number of Novel Coronavirus (COVID-19) and the probable outbreak size on the Diamond Princess cruise ship: A data-driven analysis,10.1016/j.ijid.2020.02.033,,,cc-by-nc-nd,"Backgrounds Up to February 16, 2020, 355 cases have been confirmed as having COVID-19 infection on the Diamond Princess cruise ship. It is of crucial importance to estimate the reproductive number (R0) of the novel virus in the early stage of outbreak and make a prediction of daily new cases on the ship. Method We fitted the reported serial interval (Mean and standard deviation) with a gamma distribution and applied “earlyR” package in R to estimate the R0 in the early stage of COVID-19 outbreak. We applied “projections” package in R to simulate the plausible cumulative epidemic trajectories and future daily incidence by fitting the data of existing daily incidence, a serial interval distribution, and the estimated R0 into a model based on the assumption that daily incidence obeys approximately Poisson distribution determined by daily infectiousness. Results The Maximum-Likelihood (ML) value of R0 was 2.28 for COVID-19 outbreak at early stage on the ship. The median with 95% confidence interval (CI) of R0 values was 2.28 (2.06-2.52) estimated by the bootstrap resampling method. The probable number of new cases for the next ten days would gradually increase, and the estimated cumulative cases would reach 1514 (1384-1656) at the tenth day in the future. However, if R0 value was reduced by 25% and 50%, the estimated total number of cumulative cases would be reduced to 1081 (981-1177) and 758 (697-817), respectively. Conclusion The median with 95% CI of R0 of COVID-19 was about 2.28 (2.06-2.52) during the early stage experienced on the Diamond Princess cruise ship. The future daily incidence and probable outbreak size is largely dependent on the change of R0. Unless strict infection management and control are taken, our findings indicate the potential of COVID-19 to cause greater outbreak on the ship.",2020,"Zhang, Sheng; Diao, MengYuan; Yu, Wenbo; Pei, Lei; Lin, Zhaofen; Chen, Dechang",International Journal of Infectious Diseases,3001305894,#1430,True
83c96f2a481be06a5c58552cbad2ca67ce789dc2,CZI,Identification of COVID-19 Can be Quicker through Artificial Intelligence framework using a Mobile Phone-Based Survey in the Populations when Cities/Towns Are Under Quarantine,10.1017/ice.2020.61,,,cc-by,We are proposing to use machine learning algorithms to be able to improve possible case identifications of COVID-19 more quicker when we use a mobile phone-based web survey. This will also reduce the spread in the susceptible populations.,2020,"Vazquez, Arni S.R. Srinivasa Rao; Jose A.",Infection Control & Hospital Epidemiology,2816053183,#3078,True
b0f4f2cb1c392ec68afaa865ecdd5db824ccf457,CZI,Nepal’s First Case of COVID-19 and public health response,10.1093/jtm/taaa024,,,cc-by-nc,"SARS, in 2003, spread both within a geographical region and, more significantly, to different cities from a single location, through infected travelers.4 The air-travel frequency from major cities in China to Nepal is lower compared to that of other countries.5 However, there are other factors to consider. Firstly, Nepal is an emerging tourist destination and 2020 has been declared “Visit Nepal” year with an expected 500,000 tourists. Among the total number of tourists in 2018, 153633, the second-highest number, were Chinese tourists, with the highest influx during February and December.6 COVID-19 outbreak coincides (similar to SARS) with Chinese new year during which the Chinese travel extensively, increasing chances for transmission.7 Study into coronavirus infections in Nepal, has shown the incidence to be higher in winter (DecemberFebruary).8 Furthermore, Nepal shares northern border with China with several border crossing points. Several Nepalese students study in China and in Wuhan, the epicenter of the outbreak. Thus, the potential for the spread of COVID-19 through travel and the overlap between the months of peak tourist season in Nepal and the months of the emergence of the epidemic could pose a risk to Nepal. One confirmed case in Nepal was a Nepalese student, studying in Wuhan, with symptom-onset on January 3. The infected 32-year-old male had returned on January 9 to spend winter holidays in Nepal. He had prior knowledge about the outbreak in China and visited the Sukraraj Tropical (truncated)",2020,"Shrestha, Ranish; Shrestha, Sunil; Khanal, Pratik; Bhuvan, K. C.",Journal of Travel Medicine,,#2547,True
ecd8df7900c3c07863a0ed0e1b6c5d5ecae4e651,CZI,Comparative Serological Study for the Prevalence of Anti-MERS Coronavirus Antibodies in High- and Low-Risk Groups in Qatar,10.1155/2019/1386740,,134769660,cc-by,"Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) could be asymptomatic or cause mild influenza-like illness. Therefore, the prevalence of MERS-CoV infections in the general population could be underestimated, which necessitates active surveillance to determine the epidemiological importance of asymptomatic cases. The aim of this study is to evaluate the performance of various serological assays and to estimate the seroprevalence of anti-MERS-CoV antibodies in high- and low-risk groups in Qatar. A total of 4858 samples were screened, including 4719 samples collected from healthy blood donors (BD) over a period of five years (2012-2016), 135 samples from baseline case contacts (CC) collected from individuals in close contact with three positive PCR-confirmed patients (CP), and four samples from MERS-CoV CP. Initial screening using anti-MERS-CoV IgG (IgG rS1-ELISA kit) revealed ten reactive samples from BD (10/4719, 0.21%), one from CC (1/135, 0.74%), and three from CP (3/4, 75%). Samples from CP but not from BD were also reactive by whole-virus anti-MERS-CoV IgG (n = 3/4) and IgM (n = 1/4) indirect immunefluorescent tests (IIFT) and pseudoparticle neutralization test (ppNT). The reactive sample from CC was also confirmed by ppNT. Surprisingly, one out of thirteen (7.7%) randomly selected IgG rS1-ELISA-negative BD samples from the initial screening was reactive by the IgM-IIFT (but not by the IgG-IIFT) and was subsequently confirmed by ppNT. All IgG rS1-ELISA-reactive samples from BD exhibited considerable reactivity to the four circulating human coronaviruses (HKU1, OC43, 229E, and NL63). Cross-reactivity with SARS was only reported for samples from CP using IgG and IgM-IIFT. In conclusion, we report a low prevalence of anti-MERS antibodies in the general population, which coincides with the low number of all reported cases by the time of our study (2017) in Qatar (n = 21). The false-positive results and the observed cross-reactivity between MERS-CoV and other circulating human coronavirus necessitate more detailed evaluation of available serological assays.",2019,"Al Kahlout, Reham A.; Nasrallah, Gheyath K.; Farag, Elmoubasher A.; Wang, Lingshu; Lattwein, Erik; Müller, Marcel A.; El Zowalaty, Mohamed E.; Al Romaihi, Hamad E.; Graham, Barney S.; Al Thani, Asmaa A.; Yassine, Hadi M.",Journal of Immunology Research,2913478568,#2447,True
4a077b9696d19b7d7fa3e71560b7fd5f414a4d19,CZI,"Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020",10.2807/1560-7917.ES.2020.25.5.2000062,,,cc-by,"In January 2020, an increasing number of cases confirmed to be infected with 2019-nCoV were detected outside Wuhan. For 88 cases detected between 20 and 28 January, the travel history (to and) from Wuhan is known, as well as their symptom onset date. Their ages range from 2 to 72 years of age (information missing for four cases); 31 were female and 57 were male. During this initial stage of the epidemic, it is most likely that these travellers were infected in Wuhan. Consequently, their time spent in Wuhan can be taken as the duration of exposure to infection. Of these 88 cases with known travel history, 63 were Wuhan residents who travelled elsewhere and 25 were visitors who stayed in Wuhan for a limited time. By taking the date of symptom onset and travel history together, we inferred the possible incubation period for each of these cases. The data used for this analysis has been translated from Chinese sources such as provincial centres of disease control, and made publicly available [8]. We took the data as available on 29 January 2020 (Supplementary Material S1).",2020,"Backer, Jantien A; Klinkenberg, Don; Wallinga, Jacco",Eurosurveillance,,#668,True
0938d2fb07611897abf38cea727ddbeea77b73d9,CZI,Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess,10.3390/jcm9030657,,32121356,cc-by,"To understand the time-dependent risk of infection on a cruise ship, the Diamond Princess, I estimated the incidence of infection with novel coronavirus (COVID-19). The epidemic curve of a total of 199 confirmed cases was drawn, classifying individuals into passengers with and without close contact and crew members. A backcalculation method was employed to estimate the incidence of infection. The peak time of infection was seen for the time period from 2 to 4 February 2020, and the incidence has abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 February on which a movement restriction policy was imposed. Without the intervention from 5 February, it was predicted that the cumulative incidence with and without close contact would have been as large as 1373 (95% CI: 570, 2176) and 766 (95% CI: 587, 946) cases, respectively, while these were kept to be 102 and 47 cases, respectively. Based on an analysis of illness onset data on board, the risk of infection among passengers without close contact was considered to be very limited. Movement restriction greatly reduced the number of infections from 5 February onwards.",2020,"Nishiura, Hiroshi",J Clin Med,3005847234,#3329,True
09de57e5401565a1e80361d32b09ce66b3a988c8,CZI,Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies,10.3390/v12030254,,,cc-by,"The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.",2020,"Ahmed, F. Syed; Quadeer, A. Ahmed; McKay, R. Matthew",Viruses,3005472135,#2017,True
6e5ed49cd3824f3c7c435bf91302ad07f979dece,CZI,Frontiers in antiviral therapy and immunotherapy,10.1002/cti2.1115,,,cc-by,,2020,"Heaton, Steven M",Clinical & Translational Immunology,2956917138,#1302,False
0f34f180295196b73c5bf7c4892fb023d388cb15,CZI,2019-nCoV in context: lessons learned?,10.1016/S2542-5196(20)30035-8,,,cc-by,,2020,"Kock, Richard A.; Karesh, William B.; Veas, Francisco; Velavan, Thirumalaisamy P.; Simons, David; Mboera, Leonard E. G.; Dar, Osman; Arruda, Liã Bárbara; Zumla, Alimuddin",The Lancet Planetary Health,3004999328,#513,True
d4b843968ab01451c9553576eff63a52ad8ba9a4,CZI,Serial interval of novel coronavirus (COVID-19) infections,10.1016/j.ijid.2020.02.060,,,cc-by-nc-nd,"Objective To estimate the serial interval of novel coronavirus (COVID-19) from information on 28 infector-infectee pairs. Methods We collected dates of illness onset for primary cases (infectors) and secondary cases (infectees) from published research articles and case investigation reports. We subjectively ranked the credibility of the data and performed analyses on both the full dataset (n = 28) and a subset of pairs with highest certainty in reporting (n = 18). In addition, we adjust for right truncation of the data as the epidemic is still in its growth phase. Results Accounting for right truncation and analyzing all pairs, we estimated the median serial interval at 4.0 days (95% credible interval [CrI]: 3.1, 4.9). Limiting our data to only the most certain pairs, the median serial interval was estimated at 4.6 days (95% CrI: 3.5, 5.9). Conclusions The serial interval of COVID-19 is close to or shorter than its median incubation period. This suggests that a substantial proportion of secondary transmission may occur prior to illness onset. The COVID-19 serial interval is also shorter than the serial interval of severe acute respiratory syndrome (SARS), indicating that calculations made using the SARS serial interval may introduce bias.",2020,"Nishiura, Hiroshi; Linton, Natalie M.; Akhmetzhanov, Andrei R.",International Journal of Infectious Diseases,3004658686,#4488,True
43ac139b156b7a9397d9da995694319fdeeba0f4,CZI,Recommended psychological crisis intervention response to the 2019 novel coronavirus pneumonia outbreak in China: a model of West China Hospital,10.1093/pcmedi/pbaa006,,,cc-by-nc,"The novel coronavirus pneumonia (COVID-19)epidemic has brought serious social psychological impact to the Chinese people, especially those quarantined and thus with limited access to face-to-face communication and traditional social psychological interventions. To better deal with the urgent psychological problems of people involved in the COVID-19 epidemic, we developed a new psychological crisis intervention model by utilizing internet technology. This new model, one of West China Hospital, integrates physicians, psychiatrists, psychologists and social workers into Internet platforms to carry out psychological intervention to patients, their families and medical staff. We hope this model will make a sound basis for developing a more comprehensive psychological crisis intervention response system that is applicable for urgent social and psychological problems.",2020,"Zhang, Jun; Wu, Weili; Zhao, Xin; Zhang, Wei",Precision Clinical Medicine,3003487504,#1181,True
ebfc471829e1303889bd23779d1c2ffb9467ab7e,CZI,Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province,10.1097/CM9.0000000000000744,,32044814,cc-by-nc-nd,"BACKGROUND: A novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyzed the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak. METHODS: Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens. RESULTS: None of the 137 patients (61 males, 76 females, aged 20-83 years, mean age 55 ± 16 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their condition. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea. CONCLUSIONS: The majority of patients with 2019-nCoV coronavirus pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.",2020,"Kui, Liu; Fang, Yuan-Yuan; Deng, Yan; Liu, Wei; Wang, Mei-Fang; Ma, Jing-Ping; Xiao, Wei; Wang, Ying-Nan; Zhong, Min-Hua; Li, Cheng-Hong; Li, Guang-Cai; Liu, Hui-Guo",Chin Med J (Engl),3006485704,#691,True
b70d27459fd8143edf76721da40cdbca399c9fb1,CZI,Science in the fight against the novel coronavirus disease,10.1097/CM9.0000000000000777,,32118642,cc-by-nc-nd,,2020,"Wang, Jian-Wei; Cao, Bin; Wang, Chen",Chin Med J (Engl),2120794924,#3282,True
9ec258353291e981ef7eeb36111794c40b15c752,CZI,The outbreak of COVID-19: An overview,10.1097/jcma.0000000000000270,,32134861,cc-by-nc-nd,"In late December 2019, a previous unidentified coronavirus, currently named as the 2019 novel coronavirus#, emerged from Wuhan, China, and resulted in a formidable outbreak in many cities in China and expanded globally, including Thailand, Republic of Korea, Japan, United States, Philippines, Viet Nam, and our country (as of 2/6/2020 at least 25 countries). The disease is officially named as Coronavirus Disease-2019 (COVID-19, by WHO on February 11, 2020). It is also named as Severe Pneumonia with Novel Pathogens on January 15, 2019 by the Taiwan CDC, the Ministry of Health and is a notifiable communicable disease of the fifth category. COVID-19 is a potential zoonotic disease with low to moderate (estimated 2%-5%) mortality rate. Person-to-person transmission may occur through droplet or contact transmission and if there is a lack of stringent infection control or if no proper personal protective equipment available, it may jeopardize the first-line healthcare workers. Currently, there is no definite treatment for COVID-19 although some drugs are under investigation. To promptly identify patients and prevent further spreading, physicians should be aware of the travel or contact history of the patient with compatible symptoms.",2020,"Wu, Y. C.; Chen, C. S.; Chan, Y. J.",Journal of the Chinese Medical Association : JCMA,1757890151,#5321,True
ead6fda7cdb2bb2469ff48365833bd63d0b7dd1a,CZI,Estimation of the Transmission Risk of the 2019-nCoV and Its Implication for Public Health Interventions,10.3390/jcm9020462,,,cc-by,"Since the emergence of the first cases in Wuhan, China, the novel coronavirus (2019-nCoV) infection has been quickly spreading out to other provinces and neighboring countries. Estimation of the basic reproduction number by means of mathematical modeling can be helpful for determining the potential and severity of an outbreak and providing critical information for identifying the type of disease interventions and intensity. A deterministic compartmental model was devised based on the clinical progression of the disease, epidemiological status of the individuals, and intervention measures. The estimations based on likelihood and model analysis show that the control reproduction number may be as high as 6.47 (95% CI 5.71–7.23). Sensitivity analyses show that interventions, such as intensive contact tracing followed by quarantine and isolation, can effectively reduce the control reproduction number and transmission risk, with the effect of travel restriction adopted by Wuhan on 2019-nCoV infection in Beijing being almost equivalent to increasing quarantine by a 100 thousand baseline value. It is essential to assess how the expensive, resource-intensive measures implemented by the Chinese authorities can contribute to the prevention and control of the 2019-nCoV infection, and how long they should be maintained. Under the most restrictive measures, the outbreak is expected to peak within two weeks (since 23 January 2020) with a significant low peak value. With travel restriction (no imported exposed individuals to Beijing), the number of infected individuals in seven days will decrease by 91.14% in Beijing, compared with the scenario of no travel restriction.",2020,"Tang, Biao; Wang, Xia; Li, Qian; Bragazzi, Nicola Luigi; Tang, Sanyi; Xiao, Yanni; Wu, Jianhong",Journal of Clinical Medicine,3003403425,#535,True
a14b5655cb13ed64cb8cff7c806a7b58c858b8b7,CZI,Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts,10.1016/S2214-109X(20)30074-7,,,cc-by-nc-nd,"Summary Background Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19. Methods We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R0), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. Findings Simulated outbreaks starting with five initial cases, an R0 of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R0 was 2·5 or 3·5 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R0 of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R0 of 2·5 more than 70% of contacts had to be traced, and for an R0 of 3·5 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R0 was 1·5. For R0 values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset. Interpretation In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. Funding Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.",2020,"Hellewell, Joel; Abbott, Sam; Gimma, Amy; Bosse, Nikos I.; Jarvis, Christopher I.; Russell, Timothy W.; Munday, James D.; Kucharski, Adam J.; Edmunds, W. John; Sun, Fiona; Flasche, Stefan; Quilty, Billy J.; Davies, Nicholas; Liu, Yang; Clifford, Samuel; Klepac, Petra; Jit, Mark; Diamond, Charlie; Gibbs, Hamish; van Zandvoort, Kevin; Funk, Sebastian; Eggo, Rosalind M.",The Lancet Global Health,3005722800,#2829,True
00e5a723d44eb9f2698c38b518eff85c00f9753b,CZI,Six weeks into the 2019 coronavirus disease (COVID-19) outbreak- it is time to consider strategies to impede the emergence of new zoonotic infections,10.1097/CM9.0000000000000760,,32097202,cc-by-nc-nd,,2020,"Harypursat, Vijay; Chen, Yao-Kai",Chin Med J (Engl),3005943294,#1985,True
fbf7b36a98caf3fa41ff9f011dbc9eec0d02609d,CZI,La comunicación científica y el acceso abierto en la contención de enfermedades: El caso del Coronavirus novel 2019 (2019-nCoV),10.35839/repis.4.1.613,,,cc-by-nc,,2020,"Arteaga-Livias, Franz K.; Rodriguez-Morales, Alfonso J.",Revista Peruana de Investigación en Salud,,#346,True
fd28e6d03eef27b0454f13ca539dc1498242a4c2,CZI,A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version),10.1186/s40779-020-0233-6,,,cc-by,"In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.",2020,"Jin, Ying-Hui; Cai, Lin; Cheng, Zhen-Shun; Cheng, Hong; Deng, Tong; Fan, Yi-Pin; Fang, Cheng; Huang, Di; Huang, Lu-Qi; Huang, Qiao; Han, Yong; Hu, Bo; Hu, Fen; Li, Bing-Hui; Li, Yi-Rong; Liang, Ke; Lin, Li-Kai; Luo, Li-Sha; Ma, Jing; Ma, Lin-Lu; Peng, Zhi-Yong; Pan, Yun-Bao; Pan, Zhen-Yu; Ren, Xue-Qun; Sun, Hui-Min; Wang, Ying; Wang, Yun-Yun; Weng, Hong; Wei, Chao-Jie; Wu, Dong-Fang; Xia, Jian; Xiong, Yong; Xu, Hai-Bo; Yao, Xiao-Mei; Yuan, Yu-Feng; Ye, Tai-Sheng; Zhang, Xiao-Chun; Zhang, Ying-Wen; Zhang, Yin-Gao; Zhang, Hua-Min; Zhao, Yan; Zhao, Ming-Juan; Zi, Hao; Zeng, Xian-Tao; Wang, Yong-Yan; Wang, Xing-Huan; Management, for the Zhongnan Hospital of Wuhan University Novel Coronavirus; Research Team, Evidence-Based Medicine Chapter of China International Exchange; Promotive Association for, Medical; Health, Care",Military Medical Research,3004824173,#405,True
7b7c71218f8d7ea1a1f8f702e4262b839bf7cc8a,CZI,Outbreak of Novel Coronavirus (SARS-Cov-2): First Evidences From International Scientific Literature and Pending Questions,10.3390/healthcare8010051,,32120965,cc-by,"On 31 December, 2019, a cluster of 27 pneumonia cases of unknown etiology was reported by Chinese health authorities in Wuhan City (China) [...].",2020,"Amodio, Emanuele; Vitale, Francesco; Cimino, Livia; Casuccio, Alessandra; Tramuto, Fabio",Healthcare (Basel),3005538648,#3464,True
823305045f63acc52d90c2a299b25fc8f4ebe587,CZI,"Epidemiological Identification of A Novel Pathogen in Real Time: Analysis of the Atypical Pneumonia Outbreak in Wuhan, China, 2019-2020",10.3390/jcm9030637,,32120913,cc-by,"Virological tests have now shown conclusively that a novel coronavirus is causing the 2019-2020 atypical pneumonia outbreak in Wuhan, China. We demonstrate that non-virological descriptive characteristics could have determined that the outbreak is caused by a novel pathogen in advance of virological testing. Characteristics of the ongoing outbreak were collected in real time from two medical social media sites. These were compared against characteristics of eleven pathogens that have previously caused cases of atypical pneumonia. The probability that the current outbreak is due to ""Disease X"" (i.e., previously unknown etiology) as opposed to one of the known pathogens was inferred, and this estimate was updated as the outbreak continued. The probability (expressed as a percentage) that Disease X is driving the outbreak was assessed as over 29% on 31 December 2019, one week before virus identification. After some specific pathogens were ruled out by laboratory tests on 5 January 2020, the inferred probability of Disease X was over 49%. We showed quantitatively that the emerging outbreak of atypical pneumonia cases is consistent with causation by a novel pathogen. The proposed approach, which uses only routinely observed non-virological data, can aid ongoing risk assessments in advance of virological test results becoming available.",2020,"Jung, Sung-Mok; Kinoshita, Ryo; Thompson, Robin N.; Linton, Natalie M.; Yang, Yichi; Akhmetzhanov, Andrei R.; Nishiura, Hiroshi",J Clin Med,3003574291,#3387,True
247161ad51b7f362e9cadfcd39e94dd6a1a26ca3,CZI,"A conceptual model for the outbreak of Coronavirus disease 2019 (COVID-19) in Wuhan, China with individual reaction and governmental action",10.1016/j.ijid.2020.02.058,,,cc-by-nc-nd,"The ongoing Coronavirus Disease 2019 (COVID-19) outbreak, originated in the end of 2019 in Wuhan, China, has claimed more than 2200 lives and posed a huge threat to global public health. The Chinese government has implemented control measures including setting up special hospitals and travel restriction to mitigate the spread. We propose conceptual models for the outbreak in Wuhan with the consideration of individual behavioural reaction and governmental actions, e.g., holiday extension, travel restriction, hospitalisation and quarantine. We employed the estimates of these two key components from the 1918 influenza pandemic in London, United Kingdom, incorporated zoonotic introductions and the emigration, then computed future trends and the reporting ratio. The model is concise in structure, and it successfully captures the course of the COVID-19 outbreak, and thus sheds light on understanding the trends of the outbreak.",2020,"Lin, Qianying; Zhao, Shi; Gao, Daozhou; Lou, Yijun; Yang, Shu; Musa, Salihu S.; Wang, Maggie H.; Cai, Yongli; Wang, Weiming; Yang, Lin; He, Daihai",International Journal of Infectious Diseases,2604381070,#4507,True
4ecbacf61daab591e76f7471eb6e7fc1a4e0ed70,CZI,Potential role of inanimate surfaces for the spread of coronaviruses and their inactivation with disinfectant agents,10.1016/j.infpip.2020.100044,,,cc-by-nc-nd,"Summary The novel human coronavirus 2019-nCoV has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described, probably via droplets but possibly also via contaminated hands or surfaces. In a recent review on the persistence of human and veterinary coronaviruses on inanimate surfaces it was shown that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days. Some disinfectant agents effectively reduce coronavirus infectivity within 1 minute such 62% - 71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite. Other compounds such as 0.05% - 0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. An effective surface disinfection may help to ensure an early containment and prevention of further viral spread.",2020,"Kampf, Günter",Infection Prevention in Practice,3006062275,#867,True
804a9591280b7f64fa79cd3e4a9358976b084ffb,CZI,Revisiting the dangers of the coronavirus in the ophthalmology practice,10.1038/s41433-020-0790-7,,,cc-by,"A possible threat in the ophthalmology clinic While the 2019-nCoV transmission route is still unknown, countries have been preparing measures based on past experiences with coronaviruses namely SARS-CoV and MERS-CoV. These viruses transmit primarily through droplets and other bodily secretions. In the ophthalmology practice, healthcare workers may be particularly susceptible to these infections. Firstly, ophthalmologists are extremely reliant on physical examination during patient consultation. Of particular concern is the proximity between the patient and ophthalmologist during the slit lamp microscope examination. It has been shown that droplets from a cough or sneeze can be propelled for up to 6?m [8], a range that definitely encompasses the distance between the patient and ophthalmologist. Secondly, during the SARS-CoV epidemic, clinical reports have suggested tears as a medium of infection. In a case series by Loon et al., it was shown that viral RNA of the SARS-CoV can be detected by reverse-transcription polymerase chain reaction (RT-PCR) from the tears of infected individuals [9]. While anecdotal in nature, such accounts highlight the possible infectivity of tears, a fluid which ophthalmologists and instruments come in contact on a daily basis. If true, this represents a crucial need for further development of disinfection and personal protective equipment (PPE) protocols for the ophthalmology clinic.SN - 1476-5454",2020,"Seah, Ivan; Su, Xinyi; Lingam, Gopal",Eye,3005477973,#375,True
12d267205009c178b6a50506db717ff650d93415,CZI,A pneumonia outbreak associated with a new coronavirus of probable bat origin,10.1038/s41586-020-2012-7,,32015507,cc-by,"Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome-related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats(1-4). Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans(5-7). Here we report the identification and characterization of a novel coronavirus (2019-nCoV) which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started from 12 December 2019, has caused 2,050 laboratory-confirmed infections with 56 fatal cases by 26 January 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The 2019-nCoV virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.",2020,"Zhou, Peng; Yang, Xing-Lou; Wang, Xian-Guang; Hu, Ben; Zhang, Lei; Zhang, Wei; Si, Hao-Rui; Zhu, Yan; Li, Bei; Huang, Chao-Lin; Chen, Hui-Dong; Chen, Jing; Luo, Yun; Guo, Hua; Jiang, Ren-Di; Liu, Mei-Qin; Chen, Ying; Shen, Xu-Rui; Wang, Xi; Zheng, Xiao-Shuang; Zhao, Kai; Chen, Quan-Jiao; Deng, Fei; Liu, Lin-Lin; Yan, Bing; Zhan, Fa-Xian; Wang, Yan-Yi; Xiao, Geng-Fu; Shi, Zheng-Li",Nature,3004280078,#246,True
f3fa89e819a64d2d6c74f6d590661ca435878c26,CZI,Overview of The 2019 Novel Coronavirus (2019-nCoV): The Pathogen of Severe Specific Contagious Pneumonia (SSCP),10.1097/JCMA.0000000000000270,,32049687,cc-by-nc-nd,"In late December 2019 a previous unidentified coronavirus, currently named as the 2019 novel coronavirus (2019-nCoV), emerged from Wuhan, China and resulted in a formidable outbreak in many cities in China and expanding globally, including Thailand, Republic of Korea, Japan, USA, Philippines, Viet Nam, and our country (as of 2/6/2020 at least 25 countries). The disease is officially named as the Severe Specific Contagious Pneumonia (SSCP) in 1/15/2019 and is a notifiable communicable disease of the 5 category by the Taiwan CDC, the Ministry of Health. SSCP is a potential zoonotic disease with low to moderate (estimated 2-5%) mortality rate. Person-to-person transmission may occur through droplet or contact transmission and jeopardized first-line healthcare workers if lack of stringent infection control or no proper personal protective equipment available. Currently, there is no definite treatment for SSCP although some drugs are under investigation. To promptly identify patients and prevent further spreading, physicians should be aware of travel or contact history for patients with compatible symptoms.",2020,"Wu, Yi-Chi; Chen, Ching-Sung; Chan, Yu-Jiun",J Chin Med Assoc,3006472059,#717,True
018269476cd191365d6b8bed046078aea07c8c01,CZI,A mathematical model for simulating the phase-based transmissibility of a novel coronavirus,10.1186/s40249-020-00640-3,,,cc-by,"Background As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. The virus was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020. This study aimed to develop a mathematical model for calculating the transmissibility of the virus. Methods In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probably be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market (reservoir) to people, we simplified the model as Reservoir-People (RP) transmission network model. The next generation matrix approach was adopted to calculate the basic reproduction number (R 0) from the RP model to assess the transmissibility of the SARS-CoV-2. Results The value of R 0 was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58. Conclusions Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea.",2020,"Yin, Tian-Mu Chen; Jia, Rui; Qiu-Peng, Wang; Ze-Yu, Zhao; Jing-An, Cui; Ling",Infectious Diseases of Poverty,2998953329,#2762,True
489040d34aa5dc8e6eba3d4e9d3d48f0bcc6061f,CZI,"Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China [version 2; peer review: 2 approved]",10.12688/f1000research.22211.2,,,cc-by,"A novel coronavirus (2019-nCoV) originating in Wuhan, China presents a potential respiratory viral pandemic to the world population. Current efforts are focused on containment and quarantine of infected individuals. Ultimately, the outbreak could be controlled with a protective vaccine to prevent 2019-nCoV infection. While vaccine research should be pursued intensely, there exists today no therapy to treat 2019-nCoV upon infection, despite an urgent need to find options to help these patients and preclude potential death. Herein, I review the potential options to treat 2019-nCoV in patients, with an emphasis on the necessity for speed and timeliness in developing new and effective therapies in this outbreak. I consider the options of drug repurposing, developing neutralizing monoclonal antibody therapy, and an oligonucleotide strategy targeting the viral RNA genome, emphasizing the promise and pitfalls of these approaches. Finally, I advocate for the fastest strategy to develop a treatment now, which could be resistant to any mutations the virus may have in the future. The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain (ACE2-Fc), providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. The ACE2-Fc therapy would also supplement decreased ACE2 levels in the lungs during infection, thereby directly treating acute respiratory distress pathophysiology as a third mechanism of action. The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken. Such a treatment could help infected patients before a protective vaccine is developed and widely available in the coming months to year(s).",2020,"Kruse, Robert L.",F1000Research,3004071935,#1971,True
97040e1e32165ddc6f5ac806f9d970c4141c561e,CZI,2019-novel Coronavirus (2019-nCoV): estimating the case fatality rate - a word of caution,10.4414/smw.2020.20203,,32031234,cc-by-nc-nd,,2020,"Battegay, Manuel; Kuehl, Richard; Tschudin-Sutter, Sarah; Hirsch, Hans H.; Widmer, Andreas F.; Neher, Richard A.",Swiss Med Wkly,3005409672,#491,True
09c84b9de7fc5c3fed4736e7a3cd45e112377042,CZI,COVID-19 in the Shadows of MERS-CoV in the Kingdom of Saudi Arabia,10.2991/jegh.k.200218.003,,,cc-by-nc,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has plagued the Middle East since it was first reported in 2012. Recently, at the end of December 2019, a cluster of pneumonia cases were reported from Wuhan city, Hubei Province, China, linked to a wet seafood market with a new coronavirus identified as the etiologic agent currently named SARS-CoV-2. Most cases are in Mainland China with international spread to 25 countries. The novelty of the virus, the rapid national and international spread, and the lack of therapeutic and preventative strategies have led the WHO International Health Regulation emergency committee to declare the disease as Public Health Emergency of International Concern (PHEIC) on January 30, 2020. As it relates to countries with the ongoing MERS-CoV community cases and hospital acquired infections, there will be a huge challenge for HCWs to deal with both coronaviruses, especially with the lack of standardized and approved point of care testing. This challenge will now be faced by the whole global health community dealing with COVID-19 since both coronaviruses have similar presentation. Those patients should now be tested for both MERS-CoV and SARS-CoV-2 simultaneously, and with the continuing wide international spread of SARS-CoV-2, the travel history to China in the last 14 days will be of less significance",2020,"Memish, Mazin Barry; Maha Al, Amri; Ziad, A.",Journal of Epidemiology and Global Health,2093640054,#2899,True
7af7848a33dc0c6599e902e9c155ab68fa72ffad,CZI,Communicating the Risk of Death from Novel Coronavirus Disease (COVID-19),10.3390/jcm9020580,,,cc-by,"To understand the severity of infection for a given disease, it is common epidemiological practice to estimate the case fatality risk, defined as the risk of death among cases. However, there are three technical obstacles that should be addressed to appropriately measure this risk. First, division of the cumulative number of deaths by that of cases tends to underestimate the actual risk because deaths that will occur have not yet observed, and so the delay in time from illness onset to death must be addressed. Second, the observed dataset of reported cases represents only a proportion of all infected individuals and there can be a substantial number of asymptomatic and mildly infected individuals who are never diagnosed. Third, ascertainment bias and risk of death among all those infected would be smaller when estimated using shorter virus detection windows and less sensitive diagnostic laboratory tests. In the ongoing COVID-19 epidemic, health authorities must cope with the uncertainty in the risk of death from COVID-19, and high-risk individuals should be identified using approaches that can address the abovementioned three problems. Although COVID-19 involves mostly mild infections among the majority of the general population, the risk of death among young adults is higher than that of seasonal influenza, and elderly with underlying comorbidities require additional care.",2020,"Kobayashi, Tetsuro; Jung, Sung-mok; Linton, M. Natalie; Kinoshita, Ryo; Hayashi, Katsuma; Miyama, Takeshi; Anzai, Asami; Yang, Yichi; Yuan, Baoyin; Akhmetzhanov, R. Andrei; Suzuki, Ayako; Nishiura, Hiroshi",Journal of Clinical Medicine,3005847234,#1603,True
7e8409337e69a72191475029805c6776ad43b60b,CZI,"2019-nCoV (Wuhan virus), a novel Coronavirus: Human-to-human transmission, travel-related cases, and vaccine readiness",10.3855/jidc.12425,,,cc-by,"On 31 December 2019 the Wuhan Health Commission reported a cluster of atypical pneumonia cases that was linked to a wet market in the city of Wuhan, China. The first patients began experiencing symptoms of illness in mid-December 2019. Clinical isolates were found to contain a novel coronavirus with similarity to bat coronaviruses. As of 28 January 2020, there are in excess of 4,500 laboratory-confirmed cases, with > 100 known deaths. As with the SARS-CoV, infections in children appear to be rare. Travel-related cases have been confirmed in multiple countries and regions outside mainland China including Germany, France, Thailand, Japan, South Korea, Vietnam, Canada, and the United States, as well as Hong Kong and Taiwan. Domestically in China, the virus has also been noted in several cities and provinces with cases in all but one provinence. While zoonotic transmission appears to be the original source of infections, the most alarming development is that human-to-human transmission is now prevelant. Of particular concern is that many healthcare workers have been infected in the current epidemic. There are several critical clinical questions that need to be resolved, including how efficient is human-to-human transmission? What is the animal reservoir? Is there an intermediate animal reservoir? Do the vaccines generated to the SARS-CoV or MERS-CoV or their proteins offer protection against 2019-nCoV? We offer a research perspective on the next steps for the generation of vaccines. We also present data on the use of in silico docking in gaining insight into 2019-nCoV Spike-receptor binding to aid in therapeutic development. Diagnostic PCR protocols can be found at https://www.who.int/health-topics/coronavirus/laboratory-diagnostics-for-novel-coronavirus.",2020,"Ralph, R.; Lew, J.; Zeng, T.; Francis, M.; Xue, B.; Roux, M.; Ostadgavahi, A. T.; Rubino, S.; Dawe, N. J.; Al-Ahdal, M. N.; Kelvin, D. J.; Richardson, C. D.; Kindrachuk, J.; Falzarano, D.; Kelvin, A. A.",Journal of Infection in Developing Countries,3004705239,#1512,True
24a525b0319b028b8898f731d49b84f467ae2c73,CZI,A potential role for integrins in host cell entry by SARS-CoV-2,10.1016/j.antiviral.2020.104759,,,cc-by,,2020,"Sigrist, Christian; Bridge, Alan; Le Mercier, Philippe",Antiviral Research,2163643581,#2945,True
2271485cae8757f2abdb1c2d012bb892c5421ba4,CZI,A strategy to prevent future pandemics similar to the 2019-nCoV outbreak,10.1016/j.bsheal.2020.01.003,,,cc-by-nc-nd,"A novel bat-origin coronavirus emerged in Wuhan, China in December 2019 and continues to spread across China and the world. At the time of writing, a massive global response has been implemented to control the disease as it spreads from person to person. Yet the high-risk human-wildlife interactions and interfaces that led to the emergence of SARS-CoV and of 2019-nCoV continue to exist in emerging disease hotspots globally. To prevent the next pandemic related to these interfaces, we call for research and investment in three areas: 1) surveillance among wildlife to identify the high-risk pathogens they carry; 2) surveillance among people who have contact with wildlife to identify early spillover events; and 3) improvement of market biosecurity regarding the wildlife trade. As the emergence of a novel virus anywhere can impact the furthest reaches of our connected world, international collaboration among scientists is essential to address these risks and prevent the next pandemic.",2020,"Daszak, Peter; Olival, Kevin J.; Li, Hongying",Biosafety and Health,3004767366,#416,True
19ff77e874c0706f794908e9b6878314671d385a,CZI,A distinct name is needed for the new coronavirus,10.1016/S0140-6736(20)30419-0,,,pd,,2020,"Jiang, Shibo; Shi, Zhengli; Shu, Yuelong; Song, Jingdong; Gao, George F.; Tan, Wenjie; Guo, Deyin",The Lancet,3003788575,#1297,True
22694a0a131da58c1a82a0d2d1556e0ccd8617c5,CZI,"The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health — The latest 2019 novel coronavirus outbreak in Wuhan, China - International Journal of Infectious Diseases",10.1016/j.ijid.2020.01.009,,,cc-by-nc-nd,"The city of Wuhan in China is the focus of global attention due to an outbreak of a febrile respiratory illness due to a coronavirus 2019-nCoV. In December 2019, there was an outbreak of pneumonia of unknown cause in Wuhan, Hubei province in China, with an epidemiological link to the Huanan Seafood Wholesale Market where there was also sale of live animals. Notification of the WHO on 31 Dec 2019 by the Chinese Health Authorities has prompted health authorities in Hong Kong, Macau, and Taiwan to step up border surveillance, and generated concern and fears that it could mark the emergence of a novel and serious threat to public health (WHO, 2020a; Parr, 2020).",2020,"Hui, David S.",International Journal of Infectious Diseases,,#2254,True
637939a0f462b9e821ff62fc20e9fedfe78df73e,CZI,"Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven analysis in the early phase of the outbreak",10.1016/j.ijid.2020.01.050,,,cc-by-nc-nd,"Backgrounds An ongoing outbreak of a novel coronavirus (2019-nCoV) pneumonia hit a major city of China, Wuhan, December 2019 and subsequently reached other provinces/regions of China and countries. We present estimates of the basic reproduction number,R0, of 2019-nCoV in the early phase of the outbreak. Methods Accounting for the impact of the variations in disease reporting rate, we modelled the epidemic curve of 2019-nCoV cases time series, in mainland China from January 10 to January 24, 2020, through the exponential growth. With the estimated intrinsic growth rate (γ), we estimated R0 by using the serial intervals (SI) of two other well-known coronavirus diseases, MERS and SARS, as approximations for the true unknown SI. Findings The early outbreak data largely follows the exponential growth. We estimated that the meanR0 ranges from 2.24 (95%CI: 1.96-2.55) to 3.58 (95%CI: 2.89-4.39) associated with 8-fold to 2-fold increase in the reporting rate. We demonstrated that changes in reporting rate substantially affect estimates of R0. Conclusion The mean estimate ofR0 for the 2019-nCoV ranges from 2.24 to 3.58, and significantly larger than 1. Our findings indicate the potential of 2019-nCoV to cause outbreaks.",2020,"Zhao, Shi; Lin, Qianyin; Ran, Jinjun; Musa, Salihu S.; Yang, Guangpu; Wang, Weiming; Lou, Yijun; Gao, Daozhou; Yang, Lin; He, Daihai; Wang, Maggie H.",International Journal of Infectious Diseases,3004397688,#100,True
9756bb3c608ed790d2306fc8db815a694eeca45f,CZI,Transmission routes of 2019-nCoV and controls in dental practice,10.1038/s41368-020-0075-9,,,cc-by,"A novel β-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal–oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.",2020,"Peng, Xian; Xu, Xin; Li, Yuqing; Cheng, Lei; Zhou, Xuedong; Ren, Biao",International Journal of Oral Science,659484933,#3135,True
a67012609fad77c2a1dc55f139b044c546cd13a8,CZI,Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study,10.1097/cm9.0000000000000722,,32004165,cc-by-nc-nd,"BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital of Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown beta-CoV strain in all five patients, with 99.8-99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6-87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.",2020,"Ren, L. L.; Wang, Y. M.; Wu, Z. Q.; Xiang, Z. C.; Guo, L.; Xu, T.; Jiang, Y. Z.; Xiong, Y.; Li, Y. J.; Li, H.; Fan, G. H.; Gu, X. Y.; Xiao, Y.; Gao, H.; Xu, J. Y.; Yang, F.; Wang, X. M.; Wu, C.; Chen, L.; Liu, Y. W.; Liu, B.; Yang, J.; Wang, X. R.; Dong, J.; Li, L.; Huang, C. L.; Zhao, J. P.; Hu, Y.; Cheng, Z. S.; Liu, L. L.; Qian, Z. H.; Qin, C.; Jin, Q.; Cao, B.; Wang, J. W.",Chinese medical journal,3003639008,#122,True
ce5f0965088e41390e671d3d16d65ccd777efa21,CZI,Proposal for prevention and control of the 2019 novel coronavirus disease in newborn infants,10.1136/archdischild-2020-318996,,32132140,cc-by-nc,,2020,"Li, F.; Feng, Z. C.; Shi, Y.",Archives of disease in childhood. Fetal and neonatal edition,3004790666,#4804,True
a0682c2b9aabc40d6daca4496ceec2ccd0583aab,CZI,Epitope-based peptide vaccine design and target site depiction against Middle East Respiratory Syndrome Coronavirus: An immune-informatics study,10.1186/s12967-019-2116-8,,,cc-by,"Background: Middle East Respiratory Syndrome Coronavirus (MERS-COV) is the main cause of lung and kidney infections in developing countries such as Saudi Arabia and South Korea. This infectious single-stranded, positive (+) sense RNA virus enters the host by binding to dipeptidyl-peptide receptors. Since no vaccine is yet available for MERS-COV, rapid case identification, isolation, and infection prevention strategies must be used to combat the spreading of MERS-COV infection. Additionally, there is a desperate need for vaccines and antiviral strategies. Methods: The present study used immuno-informatics and computational approaches to identify conserved B-and T cell epitopes for the MERS-COV spike (S) protein that may perform a significant role in eliciting the resistance response to MERS-COV infection. Results: Many conserved cytotoxic T-lymphocyte epitopes and discontinuous and linear B-cell epitopes were predicted for the MERS-COV S protein, and their antigenicity and interactions with the human leukocyte antigen (HLA) B7 allele were estimated. Among B-cell epitopes, QLQMGFGITVQYGT displayed the highest antigenicity-score, and was immensely immunogenic. Among T-cell epitopes, MHC class-I peptide YKLQPLTFL and MHC class-II peptide YCILEPRSG were identified as highly antigenic. Furthermore, docking analyses revealed that the predicted peptides engaged in strong bonding with the HLA-B7 allele. Conclusion: The present study identified several MERS-COV S protein epitopes that are conserved among various isolates from different countries. The putative antigenic epitopes may prove effective as novel vaccines for eradication and combating of MERS-COV infection.",2019,"Tahir Ul Qamar, M.; Saleem, S.; Ashfaq, U. A.; Bari, A.; Anwar, F.; Alqahtani, S.",Journal of Translational Medicine,2987491742,#21,True
0eb44c0cc59184754a0a2cd8ee3c8b2302a8927c,CZI,Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR,10.2807/1560-7917.ES.2020.25.3.2000045,,,cc-by,"BackgroundThe ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur.AimWe aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available.MethodsHere we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology.ResultsThe workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive - Global (EVAg), a European Union infrastructure project.ConclusionThe present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.",2020,"Corman, V. M.; Landt, O.; Kaiser, M.; Molenkamp, R.; Meijer, A.; Chu, D. K.; Bleicker, T.; Brünink, S.; Schneider, J.; Schmidt, M. L.; Mulders, D. G.; Haagmans, B. L.; van der Veer, B.; van den Brink, S.; Wijsman, L.; Goderski, G.; Romette, J. L.; Ellis, J.; Zambon, M.; Peiris, M.; Goossens, H.; Reusken, C.; Koopmans, M. P.; Drosten, C.",Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,3001195213,#233,True
90d04764b497a224a1d969f4e317fc19a5feab35,CZI,On the Coronavirus (COVID-19) Outbreak and the Smart City Network: Universal Data Sharing Standards Coupled with Artificial Intelligence (AI) to Benefit Urban Health Monitoring and Management,10.3390/healthcare8010046,,,cc-by,"As the Coronavirus (COVID-19) expands its impact from China, expanding its catchment into surrounding regions and other countries, increased national and international measures are being taken to contain the outbreak. The placing of entire cities in ‘lockdown’ directly affects urban economies on a multi-lateral level, including from social and economic standpoints. This is being emphasised as the outbreak gains ground in other countries, leading towards a global health emergency, and as global collaboration is sought in numerous quarters. However, while effective protocols in regard to the sharing of health data is emphasised, urban data, on the other hand, specifically relating to urban health and safe city concepts, is still viewed from a nationalist perspective as solely benefiting a nation’s economy and its economic and political influence. This perspective paper, written one month after detection and during the outbreak, surveys the virus outbreak from an urban standpoint and advances how smart city networks should work towards enhancing standardization protocols for increased data sharing in the event of outbreaks or disasters, leading to better global understanding and management of the same.",2020,"Allam, Zaheer; Jones, David S.",Healthcare,2558035409,#3221,True
bf20dda99538a594eafc258553634fd9195104cb,CZI,Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak,10.3390/jcm9020388,,,cc-by,"Background: In December 2019, an outbreak of respiratory illness caused by a novel coronavirus (2019-nCoV) emerged in Wuhan, China and has swiftly spread to other parts of China and a number of foreign countries. The 2019-nCoV cases might have been under-reported roughly from 1 to 15 January 2020, and thus we estimated the number of unreported cases and the basic reproduction number, R0, of 2019-nCoV. Methods: We modelled the epidemic curve of 2019-nCoV cases, in mainland China from 1 December 2019 to 24 January 2020 through the exponential growth. The number of unreported cases was determined by the maximum likelihood estimation. We used the serial intervals (SI) of infection caused by two other well-known coronaviruses (CoV), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) CoVs, as approximations of the unknown SI for 2019-nCoV to estimate R0. Results: We confirmed that the initial growth phase followed an exponential growth pattern. The under-reporting was likely to have resulted in 469 (95% CI: 403−540) unreported cases from 1 to 15 January 2020. The reporting rate after 17 January 2020 was likely to have increased 21-fold (95% CI: 18−25) in comparison to the situation from 1 to 17 January 2020 on average. We estimated the R0 of 2019-nCoV at 2.56 (95% CI: 2.49−2.63). Conclusion: The under-reporting was likely to have occurred during the first half of January 2020 and should be considered in future investigation.",2020,"Zhao, Shi; Musa, Salihu S.; Lin, Qianying; Ran, Jinjun; Yang, Guangpu; Wang, Weiming; Lou, Yijun; Yang, Lin; Gao, Daozhou; He, Daihai; Wang, Maggie H.",Journal of Clinical Medicine,3004200727,#131,True
16d4d6332fb5f17df0c487e2c9202716d01889be,CZI,SARS-CoV-2 infection in children: Transmission dynamics and clinical characteristics,10.1016/j.jfma.2020.02.009,,,cc-by-nc-nd,,2020,"Cao, Qing; Chen, Yi-Ching; Chen, Chyi-Liang; Chiu, Cheng-Hsun",Journal of the Formosan Medical Association,3005688502,#3205,True
3e5edc4ff36064478e209800a15365cd5f710756,CZI,First case of Coronavirus Disease 2019 (COVID-19) pneumonia in Taiwan,10.1016/j.jfma.2020.02.007,,,cc-by-nc-nd,"An outbreak of respiratory illness proved to be infected by a 2019 novel coronavirus, officially named Coronavirus Disease 2019 (COVID-19), was notified first in Wuhan, China, and has spread rapidly in China and to other parts of the world. Herein, we reported the first confirmed case of novel coronavirus pneumonia (NCP) imported from China in Taiwan. This case report revealed a natural course of NCP with self-recovery, which may be a good example in comparison with medical treatments.",2020,"Cheng, Shao-Chung; Chang, Yuan-Chia; Fan Chiang, Yu-Long; Chien, Yu-Chan; Cheng, Mingte; Yang, Chin-Hua; Huang, Chia-Husn; Hsu, Yuan-Nian",Journal of the Formosan Medical Association,3005657121,#2326,True
58b5c77c9fb3f68a3ad84a3f15275dc0e4554192,CZI,From SARS to COVID-19: A previously unknown SARS-CoV-2 virus of pandemic potential infecting humans – Call for a One Health approach,10.1016/j.onehlt.2020.100124,,,cc-by-nc-nd,"Human coronaviruses continue to pose a threat to human health. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 which causes coronavirus disease-2019 (COVID-19), an acute respiratory disease marked the third introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. This recent ongoing emergence of a previously unknown coronavirus in China leads to huge impacts on humans globally. Here, we discuss the outbreak in a one health context, highlighting the need for the implementation of one health measures and practices to improve human health and reduce the emergence of pandemic viruses.",2020,"El Zowalaty, Mohamed E.; Järhult, Josef D.",One Health,,#1850,True
0f5842185d3392825e5ab3768ecb832fb25a3b25,CZI,Real-Time Estimation of the Risk of Death from Novel Coronavirus (COVID-19) Infection: Inference Using Exported Cases,10.3390/jcm9020523,,,cc-by,"The exported cases of 2019 novel coronavirus (COVID-19) infection that were confirmed outside China provide an opportunity to estimate the cumulative incidence and confirmed case fatality risk (cCFR) in mainland China. Knowledge of the cCFR is critical to characterize the severity and understand the pandemic potential of COVID-19 in the early stage of the epidemic. Using the exponential growth rate of the incidence, the present study statistically estimated the cCFR and the basic reproduction number—the average number of secondary cases generated by a single primary case in a naïve population. We modeled epidemic growth either from a single index case with illness onset on 8 December, 2019 (Scenario 1), or using the growth rate fitted along with the other parameters (Scenario 2) based on data from 20 exported cases reported by 24 January 2020. The cumulative incidence in China by 24 January was estimated at 6924 cases (95% confidence interval [CI]: 4885, 9211) and 19,289 cases (95% CI: 10,901, 30,158), respectively. The latest estimated values of the cCFR were 5.3% (95% CI: 3.5%, 7.5%) for Scenario 1 and 8.4% (95% CI: 5.3%, 12.3%) for Scenario 2. The basic reproduction number was estimated to be 2.1 (95% CI: 2.0, 2.2) and 3.2 (95% CI: 2.7, 3.7) for Scenarios 1 and 2, respectively. Based on these results, we argued that the current COVID-19 epidemic has a substantial potential for causing a pandemic. The proposed approach provides insights in early risk assessment using publicly available data.",2020,"Jung, Sung-mok; Akhmetzhanov, Andrei R.; Hayashi, Katsuma; Linton, Natalie M.; Yang, Yichi; Yuan, Baoyin; Kobayashi, Tetsuro; Kinoshita, Ryo; Nishiura, Hiroshi",Journal of Clinical Medicine,3005847234,#965,True
9b0c87f808b1b66f2937d7a7acb524a756b6113b,CZI,"Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review",10.3390/jcm9030623,,,cc-by,"Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.",2020,"Pang, Junxiong; Wang, Min Xian; Ang, Ian Yi Han; Tan, Sharon Hui Xuan; Lewis, Ruth Frances; Chen, Jacinta I. Pei; Gutierrez, Ramona A.; Gwee, Sylvia Xiao Wei; Chua, Pearleen Ee Yong; Yang, Qian; Ng, Xian Yi; Yap, Rowena K. S.; Tan, Hao Yi; Teo, Yik Ying; Tan, Chorh Chuan; Cook, Alex R.; Yap, Jason Chin-Huat; Hsu, Li Yang",Journal of Clinical Medicine,3001515529,#2155,True
cff7fb355c096e08503caf3108f7b01525318634,CZI,Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests,10.1016/j.ijid.2020.02.050,,,cc-by-nc-nd,"A severe respiratory ongoing outbreak of pneumonia associated with 2019 novel coronavirus was recently emerged in China. Here, we reported the epidemiological, clinical, laboratory and radiological characteristics of 19 suspect cases. We compared the positive ratio of 2019-nCoV nucleic acid amplification test from different samples including oropharyngeal swab, blood, urine and stool with 3different Fluorescent RT-PCR kits. Nine out of the 19 patients were detected 2019-nCoV infection using oropharyngeal swab samples, and the virus nucleic acid was also detected in eight of these nine patients using stool samples. None of positive results was identified in the blood and urine samples. Thses three different kits got the same result for each sample and the positive ratio of nucleic acid detection for 2019-nCoV was only 47.4% in the suspect patients. Therefore, it is possible that the really infected patients have been missed by using nucleic acid detection only. It might be better to make a diagnosis combining the Computed Tomography scans and the nucleic acid detection together.",2020,"Xie, Chunbao; Jiang, Lingxi; Huang, Guo; Pu, Hong; Gong, Bo; Lin, He; Ma, Shi; Chen, Xuemei; Long, Bo; Si, Guo; Yu, Hua; Jiang, Li; Yang, Xingxiang; Shi, Yi; Yang, Zhenglin",International Journal of Infectious Diseases,2081372128,#2506,True
4790e3eb0374a7f159014ef77ec42a6b9de91c29,CZI,Personal knowledge on novel coronavirus pneumonia,10.1097/CM9.0000000000000757,,32068600,cc-by-nc-nd,,2020,"Kang, Han-Yujie; Wang, Yi-Shan; Tong, Zhao-Hui",Chin Med J (Engl),3002108456,#1226,True
e4d53d6c63d62095343315894b1f882efe299f7d,CZI,"Differential diagnosis of illness in patients under investigation for the novel coronavirus (SARS-CoV-2), Italy, February 2020",10.2807/1560-7917.ES.2020.25.8.2000170,,,cc-by,,2020,"Bordi, Licia; Nicastri, Emanuele; Scorzolini, Laura; Caro, Antonino Di; Capobianchi, Maria Rosaria; Castilletti, Concetta; Lalle, Eleonora; group, on behalf of INMI COVID-19 study; Centers2, Collaborating",Eurosurveillance,2046423558,#2677,True
1c7db6e51155dadaaffd563ef1e560011b25ae92,CZI,"Novel Coronavirus Outbreak in Wuhan, China, 2020: Intense Surveillance Is Vital for Preventing Sustained Transmission in New Locations",10.3390/jcm9020498,,32054124,cc-by,"The outbreak of pneumonia originating in Wuhan, China, has generated 24,500 confirmed cases, including 492 deaths, as of 5 February 2020. The virus (2019-nCoV) has spread elsewhere in China and to 24 countries, including South Korea, Thailand, Japan and USA. Fortunately, there has only been limited human-to-human transmission outside of China. Here, we assess the risk of sustained transmission whenever the coronavirus arrives in other countries. Data describing the times from symptom onset to hospitalisation for 47 patients infected early in the current outbreak are used to generate an estimate for the probability that an imported case is followed by sustained human-to-human transmission. Under the assumptions that the imported case is representative of the patients in China, and that the 2019-nCoV is similarly transmissible to the SARS coronavirus, the probability that an imported case is followed by sustained human-to-human transmission is 0.41 (credible interval [0.27, 0.55]). However, if the mean time from symptom onset to hospitalisation can be halved by intense surveillance, then the probability that an imported case leads to sustained transmission is only 0.012 (credible interval [0, 0.099]). This emphasises the importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak will not become a global pandemic.",2020,"Thompson, Robin N.",J Clin Med,3006121899,#910,True
ffee1423c1320d7070fe9a871224a468768a4c10,CZI,"Authoritarianism, outbreaks, and information politics",10.1016/S2468-2667(20)30030-X,,,cc-by,,2020,"Kavanagh, Matthew M.",The Lancet Public Health,3006271029,#834,True
353852971069ad5794445e5c1ab6077ce23da75d,CZI,Crowdsourcing data to mitigate epidemics,10.1016/S2589-7500(20)30055-8,,,cc-by-nc-nd,,2020,"Leung, Gabriel M.; Leung, Kathy",The Lancet Digital Health,2154231974,#1386,True
fa46fb0587956a218b9b81d5aa6b2a6c7ec68126,CZI,"Should, and how can, exercise be done during a coronavirus outbreak? — An interview with Dr. Jeffrey A. Woods",10.1016/j.jshs.2020.01.005,,,cc-by-nc-nd,,2020,"Zhu, Weimo",Journal of Sport and Health Science,,#206,True
4a8852f2970eadd44d677311548ca6eea1c5079f,CZI,The novel Coronavirus (SARS-CoV-2) is a one health issue,10.1016/j.onehlt.2020.100123,,,cc-by-nc-nd,,2020,"Marty, Aileen Maria; Jones, Malcolm K.",One Health,3005802710,#2589,True
02652961663ca435c195fb0ed3e43642e04cfab3,CZI,Authors’ response: Plenty of coronaviruses but no SARS-CoV-2,10.2807/1560-7917.ES.2020.25.8.2000197,,,cc-by,,2020,"Reusken, Chantal B; Haagmans, Bart; Meijer, Adam; Corman, Victor M; Papa, Anna; Charrel, Remi; Drosten, Christian; Koopmans, Marion",Eurosurveillance,,#2561,True
913cd784df40966fdfd97281dd38d9c9b421f32e,CZI,2019 Novel Coronavirus (COVID-19) Pneumonia: Serial Computer Tomography Findings,10.3348/kjr.2020.0112,,32100486,cc-by-nc,"From December 2019, Coronavirus disease 2019 (COVID-19) pneumonia (formerly known as the 2019 novel Coronavirus [2019-nCoV]) broke out in Wuhan, China. In this study, we present serial CT findings in a 40-year-old female patient with COVID-19 pneumonia who presented with the symptoms of fever, chest tightness, and fatigue. She was diagnosed with COVID-19 infection confirmed by real-time reverse-transcriptase-polymerase chain reaction. CT showed rapidly progressing peripheral consolidations and ground-glass opacities in both lungs. After treatment, the lesions were shown to be almost absorbed leaving the fibrous lesions.",2020,"Wei, J.; Xu, H.; Xiong, J.; Shen, Q.; Fan, B.; Ye, C.; Dong, W.; Hu, F.",Korean journal of radiology,3005148615,#4414,True
2ef7ce66fc8445aa7bfabc121193e2ae0091fecb,CZI,2019-nCoV: Polite with children!,10.4081/pr.2020.8495,,,cc-by-nc,"A novel epidemic is challenging the global health care system. Starting from probably November to December 2019, another Coronavirus entered the arena of human pathogens, to be then defined 2019- nCoV [...].",2020,"Aricò, Désirée Caselli; Maurizio",Pediatric Reports. 2020;12(1),3006451293,#700,True
421f8341eae777852e0b4584e7221b39a0544518,CZI,"The Politics of Disease Epidemics: a Comparative Analysis of the SARS, Zika, and Ebola Outbreaks",10.1007/s40609-018-0123-y,,,cc-by,"Over the past few decades, disease outbreaks have become increasingly frequent and widespread. The epicenters of these outbreaks have differed, and could be linked to different economic contexts. Arguably, the responses to these outbreaks have been “political” and inherently burdensome to marginalized populations. Key lessons can be learned from exploring the narratives about the different epidemics in varying income settings. Based on a review of the published medical, social, and political literature, which was accessed using four electronic databases—PubMed, Sociological Abstracts, Scholars Portal, and Web of Science, the overall objective of this paper discuss scholars’ narratives on the “politics” of Ebola in a low-income setting, Zika virus in a middle-income setting, and SARS in a high-income setting. Various themes of the politics of epidemics were prominent in the literature. The narratives demonstrated the influence of power in whose narratives and what narratives are presented in the literature. While marginalized populations were reported to have borne the brunt of all disease outbreaks in the different contexts, the prevalence of their narratives within the reviewed literature was limited. Regardless of income setting, there is a need to give voice to the most marginalized communities during an epidemic. The experiences and narratives of those most vulnerable to an epidemic—specifically poor communities—need to be represented in the literature. This could contribute to mitigating some of the negative impact of the politics in epidemics.",2020,"Kapiriri, Lydia; Ross, Alison",Global Social Welfare,2890713974,#1136,True
ec53f9de631ca4386bc32b0947afc297418480f8,CZI,Emerging threats from zoonotic coronaviruses-from SARS and MERS to 2019-nCoV,10.1016/j.jmii.2020.02.001,,,cc-by-nc-nd,,2020,"Lee, Ping-Ing; Hsueh, Po-Ren","Journal of Microbiology, Immunology and Infection",3005473082,#224,True
1cf06efb631fff1394f207cd3ad09376ed85f8cb,CZI,"2019 novel coronavirus disease (COVID-19) in Taiwan: Reports of two cases from Wuhan, China",10.1016/j.jmii.2020.02.009,,,cc-by-nc-nd,"We reported two cases with community-acquired pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who returned from Wuhan, China in January, 2020. The reported cases highlight non-specific clinical presentations of 2019 novel coronavirus disease (COVID-19) as well as the importance of rapid laboratory-based diagnosis.",2020,"Huang, Wei-Hsuan; Teng, Ling-Chiao; Yeh, Ting-Kuang; Chen, Yu-Jen; Lo, Wei-Jung; Wu, Ming-Ju; Chin, Chun-Shih; Tsan, Yu-Tse; Lin, Tzu-Chieh; Chai, Jyh-Wen; Lin, Chin-Fu; Tseng, Chien-Hao; Liu, Chia-Wei; Wu, Chi-Mei; Chen, Po-Yen; Shi, Zhi-Yuan; Liu, Po-Yu","Journal of Microbiology, Immunology and Infection",3005943294,#1299,True
e827d65c421e5a5ed761cc56cc2a5f06a3545a82,CZI,Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia,10.1038/s41392-020-0127-9,,,cc-by,"Salvage corticosteroids treatment for critical patients with 2019-nCoV? Corticosteroids are widely used to prevent lung injury caused by severe community-acquired pneumonia (sCAP) due to their excellent pharmacological effects on the suppression of exuberant and dysfunctional systematic inflammation5. Some scholars may not support the corticosteroids treatment for novel coronavirus pneumonia (NCP), because observational studies and systematic reviews have indicated inconclusive clinical evidence on the effect of corticosteroids therapy for viral pneumonias (such as SARS, MERS and H1N1). Additionally, pulse-dose therapy or long-term administration to high dose of corticosteroids in early stage were reported to be possibly harmful6,7,8. However, these conclusions obscured the clinical benefits of corticosteroids on some subgroups of patients, particularly those with severe symptoms, as the clinical effects might be related to the indication (severities of illness), the timing of intervention, the dose and duration of corticosteroids therapy9.",2020,"Gao, Wei Zhou; Yisi, Liu; Dongdong, Tian; Cheng, Wang; Sa, Wang; Jing, Cheng; Ming, Hu; Minghao, Fang; Yue",Signal Transduction and Targeted Therapy,2337846891,#1644,True
e9457327ddb51cf3ceb3698660ff08f526a09d44,CZI,Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease,10.1097/CM9.0000000000000775,,32118640,cc-by-nc-nd,"BACKGROUND: Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aims to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia. METHODS: Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher exact test. Logistic regression analysis was performed to explore the risk factors for disease progression. RESULTS: Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 [51, 70] vs. 37 [32, 41] years, U = 4.932, P = 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 [37.8, 38.6] vs. 37.5 [37.0, 38.4]°C, U = 2.057, P = 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ = 5.611, P = 0.028) and respiratory rate (34 [18, 48] vs. 24 [16, 60] breaths/min, U = 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 [14.3, 64.8] vs. 10.6 [1.9, 33.1] mg/L, U = 1.315, P = 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ± 6.60 vs. 41.27 ± 4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio [OR], 8.546; 95% confidence interval [CI]: 1.628-44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577-25.000; P = 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036-78.147, P = 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942-40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098-50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224-34.701, P = 0.028) were risk factors for disease progression. CONCLUSIONS: Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature on admission, respiratory failure, albumin, C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.",2020,"Liu, Wei; Tao, Zhao-Wu; Lei, Wang; Ming-Li, Yuan; Kui, Liu; Ling, Zhou; Shuang, Wei; Yan, Deng; Jing, Liu; Liu, Hui-Guo; Ming, Yang; Yi, Hu",Chin Med J (Engl),2370051937,#3344,True
32b10bf8534bb8843320576bbf033d983e89f692,CZI,Letter to the editor: Plenty of coronaviruses but no SARS-CoV-2,10.2807/1560-7917.ES.2020.25.8.2000171,,,cc-by,,2020,"Colson, Philippe; Scola, Bernard La; Esteves-Vieira, Vera; Ninove, Laetitia; Zandotti, Christine; Jimeno, Marie-Thérèse; Gazin, Céline; Bedotto, Marielle; Filosa, Véronique; Giraud-Gatineau, Audrey; Chaudet, Hervé; Brouqui, Philippe; Lagier, Jean-Christophe; Raoult, Didier",Eurosurveillance,1979783167,#2657,True
63af0d8b639b0abe14d9be9eaa3a135bb9a9eaf1,CZI,High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa,10.1038/s41368-020-0074-x,,,cc-by,"It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-nCov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas (TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression (FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.",2020,"Xu, Hao; Zhong, Liang; Deng, Jiaxin; Peng, Jiakuan; Dan, Hongxia; Zeng, Xin; Li, Taiwen; Chen, Qianming",International Journal of Oral Science,2140051496,#1738,True
1ddf28f6c2bc0a7db607b0771748e34fb6659f51,CZI,Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses,10.3389/fmicb.2020.00298,,,cc-by,"Seven coronaviruses (CoVs) have been isolated from humans so far. Among them, three emerging pathogenic CoVs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and a newly identified CoV (2019-nCoV), once caused or continue to cause severe infections in humans, posing significant threats to global public health. SARS-CoV infection in humans (with about 10% case fatality rate) was first reported from China in 2002, while MERS-CoV infection in humans (with about 34.4% case fatality rate) was first reported from Saudi Arabia in June 2012. 2019-nCoV was first reported from China in December 2019, and is currently infecting more than 70000 people (with about 2.7% case fatality rate). Both SARS-CoV and MERS-CoV are zoonotic viruses, using bats as their natural reservoirs, and then transmitting through intermediate hosts, leading to human infections. Nevertheless, the intermediate host for 2019-nCoV is still under investigation and the vaccines against this new CoV have not been available. Although a variety of vaccines have been developed against infections of SARS-CoV and MERS-CoV, none of them has been approved for use in humans. In this review, we have described the structure and function of key proteins of emerging human CoVs, overviewed the current vaccine types to be developed against SARS-CoV and MERS-CoV, and summarized recent advances in subunit vaccines against these two pathogenic human CoVs. These subunit vaccines are introduced on the basis of full-length spike (S) protein, receptor-binding domain (RBD), non-RBD S protein fragments, and non-S structural proteins, and the potential factors affecting these subunit vaccines are also illustrated. Overall, this review will be helpful for rapid design and development of vaccines against the new 2019-nCoV and any future CoVs with pandemic potential. This review was written for the topic of Antivirals for Emerging Viruses: Vaccines and Therapeutics in the Virology section of Frontiers in Microbiology.",2020,"Du, Ning Wang; Jian, Shang; Shibo, Jiang; Lanying",Frontiers in Microbiology,2169912260,#2793,True
e5d10e5272dca2d3de5ec969be8df777adee2aa3,CZI,Novel coronavirus 2019 (COVID-19): Emergence and implications for emergency care,10.1002/emp2.12034,,,cc-by-nc-nd,"Abstract A novel coronavirus (COVID-19) causing acute illness with severe symptoms has been isolated in Wuhan, Hubei Province, China. Since its emergence, cases have been found worldwide, reminiscent of severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks over the past 2 decades. Current understanding of this epidemic remains limited due to its rapid development and available data. While occurrence outside mainland China remains low, the likelihood of increasing cases globally continues to rise. Given this potential, it is imperative that emergency clinicians understand the preliminary data behind the dynamics of this disease, recognize possible presentations of patients, and understand proposed treatment modalities.",2020,"Yee, Jane; Unger, Lucy; Zadravecz, Frank; Cariello, Paloma; Seibert, Allan; Johnson, Michael Austin; Fuller, Matthew Joseph",Journal of the American College of Emergency Physicians Open,3005586004,#1442,False
9788dc8167b08ed6cfba73a0a4606b5e53bc5e37,CZI,Emerging zoonoses: A one health challenge,10.1016/j.eclinm.2020.100300,,,cc-by,,2020,,EClinicalMedicine,2151572120,#4340,False
801bdee04f820908695b58d1d23a04d3ecbf103f,CZI,Finding equipoise: CEPI revises its equitable access policy,10.1016/j.vaccine.2019.12.055,,,cc-by-nc-nd,"Launched at Davos in January 2017 with funding from sovereign investors and philanthropic institutions, the Coalition for Epidemic Preparedness Innovations (CEPI) is an innovative partnership between public, private, philanthropic, and civil organisations whose mission is to stimulate, finance and co-ordinate vaccine development against diseases with epidemic potential in cases where market incentives fail. As of December 2019, CEPI has committed to investing up to $706 million in vaccine development. This includes 19 vaccine candidates against its priority pathogens (Lassa fever virus, Middle East respiratory syndrome coronavirus, Nipah virus, Chikungunya, Rift Valley fever) and three vaccine platforms to develop vaccines against Disease X, a novel or unanticipated pathogen. As an entity largely supported by public funds, ensuring equitable access to vaccines whose development it supports in low- and middle-income countries is CEPI’s primary focus. CEPI developed an initial equitable access policy shortly after its formation, with key stakeholders expressing strong views about its content and prescriptive nature. The CEPI board instructed that it be revisited after a year. This paper describes the process of revising the policy, and how key issues were resolved. CEPI will continue to take an iterative, rather than prescriptive, approach to its policy—one that reflects the needs of multiple stakeholders and ensures it can meet its equitable access goals.",2020,"Huneycutt, Brenda; Lurie, Nicole; Rotenberg, Sara; Wilder, Richard; Hatchett, Richard",Vaccine,3003629790,#1835,True
8bcd1c3897124adec322dffb8a315fc4e24cb17e,CZI,Origin and evolution of pathogenic coronaviruses,10.1038/s41579-018-0118-9,,30531947,cc-by,"Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs.",2019,"Cui, Jie; Li, Fang; Shi, Zheng-Li",Nat Rev Microbiol,2903899730,#1405,True
606233835c3d6d195b7d230745ccb0fded626aa7,CZI,"Distribution of the COVID-19 epidemic and correlation with population emigration from wuhan, China",10.1097/CM9.0000000000000782,,32118644,cc-by-nc-nd,"BACKGROUND: The ongoing new coronavirus pneumonia (Corona Virus Disease 2019, COVID-19) outbreak is spreading in China, but it has not yet reached its peak. Five million people emigrated from Wuhan before lockdown, potentially representing a source of virus infection. Determining case distribution and its correlation with population emigration from Wuhan in the early stage of the epidemic is of great importance for early warning and for the prevention of future outbreaks. METHODS: The official case report on the COVID-19 epidemic was collected as of January 30, 2020. Time and location information on COVID-19 cases was extracted and analyzed using ArcGIS and WinBUGS software. Data on population migration from Wuhan city and Hubei province were extracted from Baidu Qianxi, and their correlation with the number of cases was analyzed. RESULTS: The COVID-19 confirmed and death cases in Hubei province accounted for 59.91% (5806/9692) and 95.77% (204/213) of the total cases in China respectively. Hot spot provinces included Sichuan and Yunnan, which are adjacent to Hubei. The time risk of Hubei province on the following day was 1.960 times that on the previous day. The number of cases in some cities was relatively low, but the time risk appeared to be continuously rising. The correlation coefficient between the provincial number of cases and emigration from Wuhan was up to 0.943. The lockdown of 17 cities in Hubei province and the implementation of nationwide control measures efficiently prevented an exponential growth in the number of cases. CONCLUSIONS: The population that emigrated from Wuhan was the main infection source in other cities and provinces. Some cities with a low number of cases showed a rapid increase in case load. Owing to the upcoming Spring Festival return wave, understanding the risk trends in different regions is crucial to ensure preparedness at both the individual and organization levels and to prevent new outbreaks.",2020,"Chen, Ze-Liang; Zhang, Qi; Lu, Yi; Guo, Zhong-Min; Zhang, Xi; Zhang, Wen-Jun; Guo, Cheng; Liao, Cong-Hui; Li, Qian-Lin; Han, Xiao-Hu; Lu, Jia-Hai",Chin Med J (Engl),3005811358,#3436,True
919c524f19f79213e6f81aa38502c70287d273dc,CZI,"The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020",10.3390/jcm9020330,,,cc-by,"A cluster of pneumonia cases linked to a novel coronavirus (2019-nCoV) was reported by China in late December 2019. Reported case incidence has now reached the hundreds, but this is likely an underestimate. As of 24 January 2020, with reports of thirteen exportation events, we estimate the cumulative incidence in China at 5502 cases (95% confidence interval: 3027, 9057). The most plausible number of infections is in the order of thousands, rather than hundreds, and there is a strong indication that untraced exposures other than the one in the epidemiologically linked seafood market in Wuhan have occurred.",2020,"Nishiura, Hiroshi; Jung, Sung-mok; Linton, Natalie M.; Kinoshita, Ryo; Yang, Yichi; Hayashi, Katsuma; Kobayashi, Tetsuro; Yuan, Baoyin; Akhmetzhanov, Andrei R.",Journal of Clinical Medicine,3001423274,#52,True
8fb937ce37aa1ad36478e6bc9c1df60d7f594f78,CZI,The coronavirus outbreak: the central role of primary care in emergency preparedness and response,10.3399/bjgpopen20X101041,,31992543,cc-by,,2020,"Dunlop, C.; Howe, A.; Li, D.; Allen, L. N.",BJGP open,3004394961,#231,True
7721a5991adb22000506b40f511a800f879d5914,CZI,Fear of the novel coronavirus,10.3855/jidc.12496,,,cc-by,,2020,"Kelvin, D. J.; Rubino, S.",Journal of Infection in Developing Countries,3004434794,#1613,True
147de820d90c0ce89fb5ae6836ea1794b808fdf2,CZI,Voice from China: nomenclature of the novel coronavirus and related diseases,10.1097/CM9.0000000000000787,,32118646,cc-by-nc-nd,,2020,,Chin Med J (Engl),2966143089,#3475,True
b6b8a2c0c3b83decefa4174ba17271c7cad45c5b,CZI,COVID-19 R0: Magic number or conundrum?,10.4081/idr.2020.8516,,,cc-by-nc,"There is an increasing concern about COVID-19 worldwide. This is a new emerging infectious disease caused by a novel coronavirus (SARS-CoV-2), which recently broke out from the Chinese city of Wuhan and has quickly spread in China, with sporadic cases in each continent [...].",2020,"Petrosillo, Giulio Viceconte; Nicola",Infectious Disease Reports,3006407045,#1946,True
376a81a940b9cdc1b10609164d5b1a5edac60956,CZI,Virus emergentes y reemergentes: un nuevo reto para la salud mundial del milenio,10.1016/j.ram.2020.02.001,,,cc-by-nc-nd,,2020,"Cuestas, María Lujan; Minassian, María Laura",Revista Argentina de Microbiología,2136639808,#2653,True
46bf124930f3ef18bc9dd2d4ae356a45d3bae461,CZI,Chest Radiographic and CT Findings of the 2019 Novel Coronavirus Disease (COVID-19): Analysis of Nine Patients Treated in Korea,10.3348/kjr.2020.0132,,32100485,cc-by-nc,"OBJECTIVE: This study presents a preliminary report on the chest radiographic and computed tomography (CT) findings of the 2019 novel coronavirus disease (COVID-19) pneumonia in Korea. MATERIALS AND METHODS: As part of a multi-institutional collaboration coordinated by the Korean Society of Thoracic Radiology, we collected nine patients with COVID-19 infections who had undergone chest radiography and CT scans. We analyzed the radiographic and CT findings of COVID-19 pneumonia at baseline. Fisher's exact test was used to compare CT findings depending on the shape of pulmonary lesions. RESULTS: Three of the nine patients (33.3%) had parenchymal abnormalities detected by chest radiography, and most of the abnormalities were peripheral consolidations. Chest CT images showed bilateral involvement in eight of the nine patients, and a unilobar reversed halo sign in the other patient. In total, 77 pulmonary lesions were found, including patchy lesions (39%), large confluent lesions (13%), and small nodular lesions (48%). The peripheral and posterior lung fields were involved in 78% and 67% of the lesions, respectively. The lesions were typically ill-defined and were composed of mixed ground-glass opacities and consolidation or pure ground-glass opacities. Patchy to confluent lesions were primarily distributed in the lower lobes (p = 0.040) and along the pleura (p < 0.001), whereas nodular lesions were primarily distributed along the bronchovascular bundles (p = 0.006). CONCLUSION: COVID-19 pneumonia in Korea primarily manifested as pure to mixed ground-glass opacities with a patchy to confluent or nodular shape in the bilateral peripheral posterior lungs. A considerable proportion of patients with COVID-19 pneumonia had normal chest radiographs.",2020,"Yoon, Soon Ho; Lee, Kyung Hee; Kim, Jin Yong; Lee, Young Kyung; Ko, Hongseok; Kim, Ki Hwan; Park, Chang Min; Kim, Yun Hyeon",Korean J Radiol,3006643024,#2077,True
d13a685f861b0f1ba05afa6e005311ad1820fd3a,CZI,Chinese medical staff request international medical assistance in fighting against COVID-19,10.1016/S2214-109X(20)30065-6,,,cc-by,,2020,"Zeng, Yingchun; Zhen, Yan",The Lancet Global Health,2794878804,#1729,False
1ffc99bb608ef7b8ac94ed926b1025a96f8871d9,CZI,How African migrants in China cope with barriers to health care,10.1016/S2468-2667(20)30048-7,,,cc-by-nc-nd,,2020,"Bodomo, Adams; Liem, Andrian; Lin, Lavinia; Hall, Brian J.",The Lancet Public Health,2200321211,#2733,False
c8cdc074d17ad030e2de3393193a5f5afeac4ccf,CZI,Coronavirus outbreak: the role of companies in preparedness and responses,10.1016/S2468-2667(20)30051-7,,,cc-by-nc-nd,"As in previous health crises, the coronavirus disease 2019 (COVID-19) outbreak has raised questions about preparedness and emergency responses in many countries. In this crisis, what role can companies play? Public and private companies must continue to produce or provide their services, but with consideration of the health context. Many companies are involved with the COVID-19 outbreak because they are established in or work with China (client or supplier), and most have already activated their business continuity planning or equivalent. During an infectious disease outbreak like COVID-19, most large companies around the world have a major part to play, especially in terms of preparedness and emergency response. Indeed, companies should be integrated into the governmental health contingency plan developed in many countries, and by WHO and the International Labor Organization. Helped by their occupational practitioners, healthcare advisers, and safety professionals, companies that have a financial capacity and responsibilities (including governmental, federal, or state administrations) will thus have to prepare their business continuity planning for when cases of infected patients occur in the company. They also must be prepared for the potential psychosocial and psychological effects of outbreaks. All health professionals should be involved in the development and implementation of recommendations for companies and their environments",,"Fadel, Marc; Salomon, Jérôme; Descatha, Alexis",The Lancet Public Health,3004394961,#2985,False
46ef984b54bda15d5f23858a2d0a0eb64f39f5d8,CZI,Caring for persons in detention suffering with mental illness during the Covid-19 outbreak,10.1016/j.fsiml.2020.100013,,,cc-by-nc-nd,,2020,"Liebrenz, M.; Bhugra, D.; Buadze, A.; Schleifer, R.",Forensic Science International: Mind and Law,2057404917,#2194,True
99f2888fb4a7fd7ab3cb2e7e9f43f66f7e6a23ce,CZI,"Quantifying the association between domestic travel and the exportation of novel coronavirus (2019-nCoV) cases from Wuhan, China in 2020: A correlational analysis",10.1093/jtm/taaa022,,,pd,,2020,"Zhao, Shi; Zhuang, Zian; Cao, Peihua; Ran, Jinjun; Gao, Daozhou; Lou, Yijun; Yang, Lin; Cai, Yongli; Wang, Weiming; He, Daihai; Wang, Maggie H.",Journal of Travel Medicine,3003807992,#1424,True
b8daf6d2ca5045194115bf8e9f41819cd3e5b47a,CZI,Clinical presentation and outcomes of long-term care residents with coronavirus respiratory infection: A retrospective cohort study,10.1093/ofid/ofz360.2126,,,cc-by-nc-nd,"Background. Human coronaviruses (CoVs) are a major cause of respiratory infection and institutional outbreaks, yet the epidemiology and clinical outcomes of these viruses is poorly described among the elderly residing in long-term care facilities (LTCFs). Methods. We performed a retrospective cohort study of LTCF residents with positive nasopharyngeal or mid-turbinate swabs for CoVs (OC43, 229E, NL63 and HKU1) between January 2013 and December 2018. Demographic and clinical data were obtained from resident charts including clinical presentation, treatment, outcome, and transmission to other residents. Variables were compared using univariate analysis. Results. 3268 residents met inclusion criteria (median age 93 years, 90% male) comprising 7.5% (246/3268) of all positive respiratory virus specimens detected during the study period. 97(39%) of cases were associated with a respiratory outbreak while 149(61%) were sporadic cases that did not result in transmission. OC43 (52%) was the most commonly identified CoV and was more commonly associated with outbreak cases (76% vs. 37%; P < 0.001). In total, 87% of all cases had two or more of runny nose/ congestion, cough, sore throat/hoarse voice or fever. The most common symptoms among residents were cough (85%), runny nose/congestion (79%), and sore throat/ hoarse voice (59%) and only 17% of residents had a measured temperature of ≥ 37.8C. Only 6% of residents received antibiotic treatment for suspected secondary bacterial pneumonia. The 30-day mortality rate was 3.7% with 67% of deaths attributable to the CoV infection. There was no statistically significant difference in symptoms, treatment or outcomes associated with outbreaks or seasonality. Conclusion. CoVs make up an important proportion of respiratory viral infections among LTCF residents and may result in frequent outbreaks. Most residents remain afebrile and have self-limited illness while only a small minority develop secondary bacterial pneumonia and death. Given these findings the benefits of control measures should be weighed against the impact on resident quality of life.",2019,"Williams, V. R.; Pajak, D.; Salt, N.; Leis, J. A.",Open Forum Infectious Diseases,2981463336,#149,False
78360444f3b4540339efc9e7e5f2610a7e46c023,CZI,Q&A: The novel coronavirus outbreak causing COVID-19,10.1186/s12916-020-01533-w,,,cc-by,"What is COVID-19, and what do we know so far about its clinical presentation? The virus responsible for COVID-19, SARS-CoV-2, is in the species SARS-like corona viruses. At 125 nm, it is slightly larger than influenza, SARS and MERS viruses. It is almost certainly a descendant from a bat corona virus of which there are many. The closest is a virus that originated from the Rhinolophus bat which is > 96% homologous with the current SARS-CoV-2 virus. It is only 79% homologous with the original SARS CoV [1]. The near identical gene sequences of 90 analysed cases from outside of China suggests it has likely emerged after a solitary species jump in early December 2019 from an unknown (likely mammalian) intermediate host [2]. Pangolins are an endangered ant-eating mammal from which scientists in Guangzhou have shown a coronavirus with 99% homology, with a receptor binding domain identical to that of SARS-CoV-2. However, this has not been confirmed, and, in addition, the pangolin's rarity means this may not be the only mammal involved.",2020,"Heymann, Dale Fisher; David",BMC Medicine,3005943294,#2807,True
af000c5a8e181550fd16291e5d4f0f70ca9161a1,CZI,"First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020",10.2807/1560-7917.ES.2020.25.6.2000094,,,cc-by,"A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) causing a cluster of respiratory infections (coronavirus disease 2019, COVID-19) in Wuhan, China, was identified on 7 January 2020. The epidemic quickly disseminated from Wuhan and as at 12 February 2020, 45,179 cases have been confirmed in 25 countries, including 1,116 deaths. Strengthened surveillance was implemented in France on 10 January 2020 in order to identify imported cases early and prevent secondary transmission. Three categories of risk exposure and follow-up procedure were defined for contacts. Three cases of COVID-19 were confirmed on 24 January, the first cases in Europe. Contact tracing was immediately initiated. Five contacts were evaluated as at low risk of exposure and 18 at moderate/high risk. As at 12 February 2020, two cases have been discharged and the third one remains symptomatic with a persistent cough, and no secondary transmission has been identified. Effective collaboration between all parties involved in the surveillance and response to emerging threats is required to detect imported cases early and to implement adequate control measures.",2020,"Stoecklin, Sibylle Bernard; Rolland, Patrick; Silue, Yassoungo; Mailles, Alexandra; Campese, Christine; Simondon, Anne; Mechain, Matthieu; Meurice, Laure; Nguyen, Mathieu; Bassi, Clément; Yamani, Estelle; Behillil, Sylvie; Ismael, Sophie; Nguyen, Duc; Malvy, Denis; Lescure, François Xavier; Georges, Scarlett; Lazarus, Clément; Tabaï, Anouk; Stempfelet, Morgane; Enouf, Vincent; Coignard, Bruno; Levy-Bruhl, Daniel; team, Investigation",Eurosurveillance,3006007867,#868,True
95cc4248c19a3cc9a54ebcfa09fc7c80518dac5d,CZI,Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods,10.1016/j.apsb.2020.02.008,,,cc-by-nc-nd,"SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.",2020,"Wu, Canrong; Liu, Yang; Yang, Yueying; Zhang, Peng; Zhong, Wu; Wang, Yali; Wang, Qiqi; Xu, Yang; Li, Mingxue; Li, Xingzhou; Zheng, Mengzhu; Chen, Lixia; Li, Hua",Acta Pharmaceutica Sinica B,2763848918,#2121,True
4faf34d795e5ff74a886528e46268af783fe712b,CZI,Structure analysis of the receptor binding of 2019-nCoV,10.1016/j.bbrc.2020.02.071,,,cc-by,"2019-nCoV is a newly identified coronavirus with high similarity to SARS-CoV. We performed a structural analysis of the receptor binding domain (RBD) of spike glycoprotein responsible for entry of coronaviruses into host cells. The RBDs from the two viruses share 72% identity in amino acid sequences, and molecular simulation reveals highly similar ternary structures. However, 2019-nCoV has a distinct loop with flexible glycyl residues replacing rigid prolyl residues in SARS-CoV. Molecular modeling revealed that 2019-nCoV RBD has a stronger interaction with angiotensin converting enzyme 2 (ACE2). A unique phenylalanine F486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ACE2. ACE2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. Structural analysis suggests that ACE2 from these animals can potentially bind RBD of 2019-nCoV, making them all possible natural hosts for the virus. 2019-nCoV is thought to be transmitted through respiratory droplets. However, since ACE2 is predominantly expressed in intestines, testis, and kidney, fecal-oral and other routes of transmission are also possible. Finally, antibodies and small molecular inhibitors that can block the interaction of ACE2 with RBD should be developed to combat the virus.",2020,"Chen, Yun; Guo, Yao; Pan, Yihang; Zhao, Zhizhuang Joe",Biochemical and Biophysical Research Communications,3006594788,#1158,True
a6eb398b44cfa0686f072f5cdbd07372587f0ed0,CZI,Wuhan coronavirus (2019-nCoV): The need to maintain regular physical activity while taking precautions,10.1016/j.jshs.2020.02.001,,,cc-by-nc-nd,,2020,"Chen, Peijie; Mao, Lijuan; Nassis, George P.; Harmer, Peter; Ainsworth, Barbara E.; Li, Fuzhong",Journal of Sport and Health Science,3004629033,#1208,True
b921ec0b4974533423b7af989620ff4ccc5e2f79,CZI,Characterization of novel monoclonal antibodies against MERS-coronavirus spike protein,10.1016/j.virusres.2020.197863,,31945421,cc-by-nc-nd,"Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes severe pulmonary infection, with approximately 35% mortality. Spike glycoprotein (S) of MERS-CoV is a key target for vaccines and therapeutics because S mediates viral entry and membrane-fusion to host cells. Here, four different S subunit proteins, receptor-binding domain (RBD; 358-606 aa), S1 (1-751 aa), S2 (752-1296 aa), and SDeltaTM (1-1296 aa), were generated using the baculoviral system and immunized in mice to develop neutralizing antibodies. We developed 77 hybridomas and selected five neutralizing mAbs by immunization with SDeltaTM against MERS-CoV EMC/2012 strain S-pseudotyped lentivirus. However, all five mAbs did not neutralize the pseudotyped V534A mutation. Additionally, one mAb RBD-14F8 did not show neutralizing activity against pseudoviruses with amino acid substitution of L506 F or D509 G (England1 strain, EMC/2012 L506 F, and EMC/2012 D509 G), and RBD-43E4 mAb could not neutralize the pseudotyped I529 T mutation, while three other neutralizing mAbs showed broad neutralizing activity. This implies that the mutation in residue 506-509, 529, and 534 of S is critical to generate neutralization escape variants of MERS-CoV. Interestingly, all five neutralizing mAbs have binding affinity to RBD, although most mAbs generated by RBD did not have neutralizing activity. Additionally, chimeric antibodies of RBD-14F8 and RBD-43E4 with human Fc and light chain showed neutralizing effect against wild type MERS-CoV KOR/KNIH/002, similar to the original mouse mAbs. Thus, our mAbs can be utilized for the identification of specific mutations of MERS-CoV.",2020,"Goo, J.; Jeong, Y.; Park, Y. S.; Yang, E.; Jung, D. I.; Rho, S.; Park, U.; Sung, H.; Park, P. G.; Choi, J. A.; Seo, S. H.; Cho, N. H.; Lee, H.; Lee, J. M.; Kim, J. O.; Song, M.",Virus research,2999847588,#35,True
a3e8cfc509af101c522d4193c8917d6e8f68b37b,CZI,"Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series",10.1136/bmj.m606,,,cc-by-nc,"Objective To study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for coronavirus disease 2019 (covid-2019).Design Retrospective case series.Setting Seven hospitals in Zhejiang province, China.Participants 62 patients admitted to hospital with laboratory confirmed SARS-Cov-2 infection. Data were collected from 10 January 2020 to 26 January 2020.Main outcome measures Clinical data, collected using a standardised case report form, such as temperature, history of exposure, incubation period. If information was not clear, the working group in Hangzhou contacted the doctor responsible for treating the patient for clarification.Results Of the 62 patients studied (median age 41 years), only one was admitted to an intensive care unit, and no patients died during the study. According to research, none of the infected patients in Zhejiang province were ever exposed to the Huanan seafood market, the original source of the virus; all studied cases were infected by human to human transmission. The most common symptoms at onset of illness were fever in 48 (77%) patients, cough in 50 (81%), expectoration in 35 (56%), headache in 21 (34%), myalgia or fatigue in 32 (52%), diarrhoea in 3 (8%), and haemoptysis in 2 (3%). Only two patients (3%) developed shortness of breath on admission. The median time from exposure to onset of illness was 4 days (interquartile range 3-5 days), and from onset of symptoms to first hospital admission was 2 (1-4) days.Conclusion As of early February 2020, compared with patients initially infected with SARS-Cov-2 in Wuhan, the symptoms of patients in Zhejiang province are relatively mild.",2020,"Xu, Xiao-Wei; Wu, Xiao-Xin; Jiang, Xian-Gao; Xu, Kai-Jin; Ying, Ling-Jun; Ma, Chun-Lian; Li, Shi-Bo; Wang, Hua-Ying; Zhang, Sheng; Gao, Hai-Nv; Sheng, Ji-Fang; Cai, Hong-Liu; Qiu, Yun-Qing; Li, Lan-Juan",BMJ,3001118548,#1262,True
58be092086c74c58e9067121a6ba4836468e7ec3,CZI,The Author's Response: Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Pneumonia Monitored by Quantitative RT-PCR,10.3346/jkms.2020.35.e89,,32080993,cc-by-nc,,2020,"Lim, Jaegyun; Jeon, Seunghyun; Shin, Hyun Young; Kim, Moon Jung; Seong, Yu Min; Lee, Wang Jun; Choe, Kang Won; Kang, Yu Min; Lee, Baeckseung; Park, Sang Joon",J Korean Med Sci,3005657121,#1576,True
80993091f576dc7fdbec10552b45b4af5eec2b8b,CZI,"Short-term Forecasts of the COVID-19 Epidemic in Guangdong and Zhejiang, China: February 13–23, 2020",10.3390/jcm9020596,,,cc-by,"The ongoing COVID-19 epidemic continues to spread within and outside of China, despite several social distancing measures implemented by the Chinese government. Limited epidemiological data are available, and recent changes in case definition and reporting further complicate our understanding of the impact of the epidemic, particularly in the epidemic’s epicenter. Here we use previously validated phenomenological models to generate short-term forecasts of cumulative reported cases in Guangdong and Zhejiang, China. Using daily reported cumulative case data up until 13 February 2020 from the National Health Commission of China, we report 5- and 10-day ahead forecasts of cumulative case reports. Specifically, we generate forecasts using a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model, which have each been previously used to forecast outbreaks due to different infectious diseases. Forecasts from each of the models suggest the outbreaks may be nearing extinction in both Guangdong and Zhejiang; however, the sub-epidemic model predictions also include the potential for further sustained transmission, particularly in Zhejiang. Our 10-day forecasts across the three models predict an additional 65–81 cases (upper bounds: 169–507) in Guangdong and an additional 44–354 (upper bounds: 141–875) cases in Zhejiang by February 23, 2020. In the best-case scenario, current data suggest that transmission in both provinces is slowing down.",2020,"Roosa, Kimberlyn; Lee, Yiseul; Luo, Ruiyan; Kirpich, Alexander; Rothenberg, Richard; Hyman, M. James; Yan, Ping; Chowell, Gerardo",Journal of Clinical Medicine,,#1506,True
74ef189f090e07b5df4d7367b09fd4859c3f01b1,CZI,COVID-19 and artificial intelligence: protecting health-care workers and curbing the spread,10.1016/S2589-7500(20)30054-6,,,cc-by,,2020,"McCall, Becky",The Lancet Digital Health,2904251400,#1375,False
459c780b398aa89f292490a6b455845448b7d537,CZI,In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus,10.1016/j.joim.2020.02.005,,,cc-by-nc-nd,"Objective In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus (2019-nCoV), an ongoing novel coronavirus that causes pneumonia. Methods There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database. Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion (ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV interaction. In the second step we searched Chinese herbal databases to identify treatments containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb. Results Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these 26 treatments were related to regulating viral infection, immune/inflammation reactions and hypoxia response. Conclusion Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.",2020,"Zhang, Deng-hai; Wu, Kun-lun; Zhang, Xue; Deng, Sheng-qiong; Peng, Bin",Journal of Integrative Medicine,1577002143,#1346,True
519cc50b5527635a0a05f7efe73b2f30c62d9936,CZI,The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2,10.1038/s41564-020-0695-z,,,cc-by,"The present outbreak of a coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) is the third documented spillover of an animal coronavirus to humans in only two decades that has resulted in a major epidemic. The Coronaviridae Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the classification of viruses and taxon nomenclature of the family Coronaviridae, has assessed the placement of the human pathogen, tentatively named 2019-nCoV, within the Coronaviridae. Based on phylogeny, taxonomy and established practice, the CSG recognizes this virus as forming a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus, and designates it as SARS-CoV-2. In order to facilitate communication, the CSG proposes to use the following naming convention for individual isolates: SARS-CoV-2/host/location/isolate/date. While the full spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined, the independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance. This will improve our understanding of virus–host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.",2020,"Gorbalenya, Alexander E.; Baker, Susan C.; Baric, Ralph S.; de Groot, Raoul J.; Drosten, Christian; Gulyaeva, Anastasia A.; Haagmans, Bart L.; Lauber, Chris; Leontovich, Andrey M.; Neuman, Benjamin W.; Penzar, Dmitry; Perlman, Stanley; Poon, Leo L. M.; Samborskiy, Dmitry V.; Sidorov, Igor A.; Sola, Isabel; Ziebuhr, John; Coronaviridae Study Group of the International Committee on Taxonomy of, Viruses",Nature Microbiology,3005788786,#3173,True
b36310af655a9ba95c32c0d8e88e5fb445edb7a1,CZI,"Transmission potential of the novel coronavirus (COVID-19) onboard the Diamond Princess Cruises Ship, 2020",10.1016/j.idm.2020.02.003,,,cc-by-nc-nd,"An outbreak of COVID-19 developed aboard the Princess Cruises Ship during January-February 2020. Using mathematical modeling and time-series incidence data describing the trajectory of the outbreak among passengers and crew members, we characterize how the transmission potential varied over the course of the outbreak. Our estimate of the mean reproduction number in the confined setting reached values as high as ∼11, which is higher than mean estimates reported from community-level transmission dynamics in China and Singapore (approximate range: 1.1-7). Our findings suggest that Rt decreased substantially compared to values during the early phase after the Japanese government implemented an enhanced quarantine control. Most recent estimates of Rt reached values largely below the epidemic threshold, indicating that a secondary outbreak of the novel coronavirus was unlikely to occur aboard the Diamond Princess Ship.",2020,"Mizumoto, Kenji; Chowell, Gerardo",Infectious Disease Modelling,3006223500,#2901,True
a209539267a73a6fb2ed9ea4766a50687b9b8cfb,CZI,Non-invasive respiratory support for patients with novel coronavirus pneumonia: clinical efficacy and reduction in risk of infection transmission,10.1097/CM9.0000000000000761,,32097201,cc-by-nc-nd,,2020,"Xia, Jin-Gen; Zhao, Jian-Ping; Cheng, Zhen-Shun; Hu, Yi; Duan, Jun; Zhan, Qing-Yuan",Chin Med J (Engl),3005079553,#1916,True
2d1374051e0b6d5b8a3f42c4906e0a56ea1d5b9d,CZI,Uncertainties about the transmission routes of 2019 novel coronavirus,10.1111/irv.12735,,,cc-by,"The 2019 novel coronavirus (now named as SARS‐CoV‐2) caused an outbreak of SARS‐like illness in the late of December 2019. At present, the origin, susceptible population, and infection sources already have been clear.1, 2 However, the transmission routes, a key step to the epidemic control, have not yet been fully ascertained. Here, we focus on the potential transmission routes that have been investigated in the SARS‐CoV‐2 epidemic recently. SARS‐CoV‐2, similar to SARS and MERS, is predominantly spread via respiratory tract with high infectivity. It is commonly recognized that droplet transmission is the main route. Spread by aerosol is suspected to be another important route of transmission but unestablished now. Epidemiological experts, as well as the WHO, consider more evidence is needed to confirm.3 Besides, there are other routes except respiratory transmission. The previous study indicated that different human coronaviruses, such as SARS‐CoV and MERS‐CoV, can maintain infectious for a different time on inanimate surfaces.4 Meanwhile, it was reported that SARS‐CoV‐2 was also founded on the surface of the door handles, cell phones, and other items in the residential sites of confirmed cases.5 Therefore, individuals will be probably infected if they touch the nose, mouth, or eyes after contacting the contaminated items.",2020,"Han, Qingmei; Lin, Qingqing; Ni, Zuowei; You, Liangshun",Influenza and Other Respiratory Viruses,3002533591,#4142,False
ccc1cedafbb30ee3184f9fc7999f4aa457805cab,CZI,Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study,10.1016/S2589-7500(20)30026-1,,,cc-by,"Summary Background As the outbreak of coronavirus disease 2019 (COVID-19) progresses, epidemiological data are needed to guide situational awareness and intervention strategies. Here we describe efforts to compile and disseminate epidemiological information on COVID-19 from news media and social networks. Methods In this population-level observational study, we searched DXY.cn, a health-care-oriented social network that is currently streaming news reports on COVID-19 from local and national Chinese health agencies. We compiled a list of individual patients with COVID-19 and daily province-level case counts between Jan 13 and Jan 31, 2020, in China. We also compiled a list of internationally exported cases of COVID-19 from global news media sources (Kyodo News, The Straits Times, and CNN), national governments, and health authorities. We assessed trends in the epidemiology of COVID-19 and studied the outbreak progression across China, assessing delays between symptom onset, seeking care at a hospital or clinic, and reporting, before and after Jan 18, 2020, as awareness of the outbreak increased. All data were made publicly available in real time. Findings We collected data for 507 patients with COVID-19 reported between Jan 13 and Jan 31, 2020, including 364 from mainland China and 143 from outside of China. 281 (55%) patients were male and the median age was 46 years (IQR 35–60). Few patients (13 [3%]) were younger than 15 years and the age profile of Chinese patients adjusted for baseline demographics confirmed a deficit of infections among children. Across the analysed period, delays between symptom onset and seeking care at a hospital or clinic were longer in Hubei province than in other provinces in mainland China and internationally. In mainland China, these delays decreased from 5 days before Jan 18, 2020, to 2 days thereafter until Jan 31, 2020 (p=0·0009). Although our sample captures only 507 (5·2%) of 9826 patients with COVID-19 reported by official sources during the analysed period, our data align with an official report published by Chinese authorities on Jan 28, 2020. Interpretation News reports and social media can help reconstruct the progression of an outbreak and provide detailed patient-level data in the context of a health emergency. The availability of a central physician-oriented social network facilitated the compilation of publicly available COVID-19 data in China. As the outbreak progresses, social media and news reports will probably capture a diminishing fraction of COVID-19 cases globally due to reporting fatigue and overwhelmed health-care systems. In the early stages of an outbreak, availability of public datasets is important to encourage analytical efforts by independent teams and provide robust evidence to guide interventions. Funding Fogarty International Center, US National Institutes of Health.",2020,"Sun, Kaiyuan; Chen, Jenny; Viboud, Cécile",The Lancet Digital Health,3005041554,#1359,True
57df78198df2774be87635b81f850b6eeb2dd6f8,CZI,Measuring multimorbidity beyond counting diseases: systematic review of community and population studies and guide to index choice,10.1136/bmj.m160,,,cc-by,"Objectives To identify and summarise existing indices for measuring multimorbidity beyond disease counts, to establish which indices include mental health comorbidities or outcomes, and to develop recommendations based on applicability, performance, and usage.Design Systematic review.Data sources Seven medical research databases (Medline, Web of Science Core Collection, Cochrane Library, Embase, PsycINFO, Scopus, and CINAHL Plus) from inception to October 2018 and bibliographies and citations of relevant papers. Searches were limited to English language publications.Eligibility criteria for study selection Original articles describing a new multimorbidity index including more information than disease counts and not focusing on comorbidity associated with one specific disease. Studies were of adults based in the community or at population level.Results Among 7128 search results, 5560 unique titles were identified. After screening against eligibility criteria the review finally included 35 papers. As index components, 25 indices used conditions (weighted or in combination with other parameters), five used diagnostic categories, four used drug use, and one used physiological measures. Predicted outcomes included mortality (18 indices), healthcare use or costs (13), hospital admission (13), and health related quality of life (7). 29 indices considered some aspect of mental health, with most including it as a comorbidity. 12 indices are recommended for use.Conclusions 35 multimorbidity indices are available, with differing components and outcomes. Researchers and clinicians should examine existing indices for suitability before creating new ones.Systematic review registration PROSPERO CRD42017074211.",2020,"Stirland, Lucy E.; González-Saavedra, Laura; Mullin, Donncha S.; Ritchie, Craig W.; Muniz-Terrera, Graciela; Russ, Tom C.",BMJ,2080410907,#1244,True
7a07d2f6803fd33f326be4952954b321c8eaaa2b,CZI,Wuhan novel coronavirus 2019nCoV,10.31646/gbio.50,,,cc-by,"Information about the open-access article 'Wuhan novel coronavirus 2019nCoV' in DOAJ. DOAJ is an online directory that indexes and provides access to quality open access, peer-reviewed journals.",2020,"MacIntyre, C Raina",Global Biosecurity,3002186368,#602,True
a6ce4ce12c7af1cfb4d71764b963285b687e6b51,CZI,Assessing the Impact of Reduced Travel on Exportation Dynamics of Novel Coronavirus Infection (COVID-19),10.3390/jcm9020601,,,cc-by,"The impact of the drastic reduction in travel volume within mainland China in January and February 2020 was quantified with respect to reports of novel coronavirus (COVID-19) infections outside China. Data on confirmed cases diagnosed outside China were analyzed using statistical models to estimate the impact of travel reduction on three epidemiological outcome measures: (i) the number of exported cases, (ii) the probability of a major epidemic, and (iii) the time delay to a major epidemic. From 28 January to 7 February 2020, we estimated that 226 exported cases (95% confidence interval: 86,449) were prevented, corresponding to a 70.4% reduction in incidence compared to the counterfactual scenario. The reduced probability of a major epidemic ranged from 7% to 20% in Japan, which resulted in a median time delay to a major epidemic of two days. Depending on the scenario, the estimated delay may be less than one day. As the delay is small, the decision to control travel volume through restrictions on freedom of movement should be balanced between the resulting estimated epidemiological impact and predicted economic fallout.",2020,"Anzai, Asami; Kobayashi, Tetsuro; Linton, M. Natalie; Kinoshita, Ryo; Hayashi, Katsuma; Suzuki, Ayako; Yang, Yichi; Jung, Sung-mok; Miyama, Takeshi; Akhmetzhanov, R. Andrei; Nishiura, Hiroshi",Journal of Clinical Medicine,3005118804,#1873,True
194f563839d8eccfdbc1d7f63a33529c42c96ec2,CZI,Imaging changes of severe COVID-19 pneumonia in advanced stage,10.1007/s00134-020-05990-y,,,cc-by-nc,"We recently reported in Intensive Care Medicine the imaging changes of acute stage from a case of 75-year-old male patient with severe COVID-19 pneumonia combined acute respiratory distress syndrome (ARDS), septic shock, and multiple organ disfunction syndrome (MODS) who had a history of 10-year hypertension and 1-year diabetes. He presently received advanced life support treatment including respiratory support (invasive mechanical ventilation) and circulatory support (vasoconstrictor assistance), as well as intermittent renal replacement therapy (IRRT) in intensive care unit (ICU) of our hospital—a tertiary teaching hospital of medical university. Because his MODS still existed on the day 20 after symptom onset, we had to re-examine the chest computed tomographic (CT). The results showed that early changes of reticular pulmonary fibrosis appeared in Panels D, E, and F (marked by green arrows), compensatory emphysema occurred in Panels D and E (marked by blue arrows), and pulmonary cavity formation appeared in Panel F (marked by blue arrows), compared with acute stage of the day 5 after symptom onset, inflammatory lesions and ground glass shadow of Panels A and B (marked by red arrows), as well as septal line of Panel C (marked by yellow arrows). Presently, this patient is still under the condition of advanced life support therapy (Fig. 1).ER -",2020,"Zhang, Wei",Intensive Care Medicine,3006643024,#3025,False
1f5c1597a84ed1d4f84c488cd19098a091a3d513,CZI,"Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARSCoV-2): Facts and myths",10.1016/j.jmii.2020.02.012,,,cc-by-nc-nd,"Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2,000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treatment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2.",2020,"Lai, Chih-Cheng; Liu, Yen Hung; Wang, Cheng-Yi; Wang, Ya-Hui; Hsueh, Shun-Chung; Yen, Muh-Yen; Ko, Wen-Chien; Hsueh, Po-Ren","Journal of Microbiology, Immunology and Infection",2029688661,#4530,True
b603913495d3cbce15eff09e645007cdf42a6e1b,CZI,Molecular Diagnosis of a Novel Coronavirus (2019-nCoV) Causing an Outbreak of Pneumonia,10.1093/clinchem/hvaa029,,32031583,pd,"BACKGROUND: A novel coronavirus of zoonotic origin (2019-nCoV) has recently been identified in patients with acute respiratory disease. This virus is genetically similar to SARS coronavirus and bat SARS-like coronaviruses. The outbreak was initially detected in Wuhan, a major city of China, but has subsequently been detected in other provinces of China. Travel-associated cases have also been reported in a few other countries. Outbreaks in health care workers indicate human-to-human transmission. Molecular tests for rapid detection of this virus are urgently needed for early identification of infected patients. METHODS: We developed two 1-step quantitative real-time reverse-transcription PCR assays to detect two different regions (ORF1b and N) of the viral genome. The primer and probe sets were designed to react with this novel coronavirus and its closely related viruses, such as SARS coronavirus. These assays were evaluated using a panel of positive and negative controls. In addition, respiratory specimens from two 2019-nCoV-infected patients were tested. RESULTS: Using RNA extracted from cells infected by SARS coronavirus as a positive control, these assays were shown to have a dynamic range of at least seven orders of magnitude (2x10-4-2000 TCID50/reaction). Using DNA plasmids as positive standards, the detection limits of these assays were found to be below 10 copies per reaction. All negative control samples were negative in the assays. Samples from two 2019-nCoV-infected patients were positive in the tests. CONCLUSIONS: The established assays can achieve a rapid detection of 2019n-CoV in human samples, thereby allowing early identification of patients.",2020,"Chu, Daniel K. W.; Pan, Yang; Cheng, Samuel M. S.; Hui, Kenrie P. Y.; Krishnan, Pavithra; Liu, Yingzhi; Ng, Daisy Y. M.; Wan, Carrie K. C.; Yang, Peng; Wang, Quanyi; Peiris, Malik; Poon, Leo L. M.",Clin Chem,3003637715,#545,True
ed3dae51cc8af4b99b820ce4eaf28f9c9995b060,CZI,Are children less susceptible to COVID-19?,10.1016/j.jmii.2020.02.011,,,cc-by-nc-nd,,2020,"Lee, Ping-Ing; Hu, Ya-Li; Chen, Po-Yen; Huang, Yhu-Chering; Hsueh, Po-Ren","Journal of Microbiology, Immunology and Infection",2415654588,#1967,True
96f65d71931741ea4668f2fbcae54a8d8905abac,CZI,From SARS-CoV to 2019-nCoV Outbreak: Similarities in the Early Epidemics and Prediction of Future Trends,10.1097/CM9.0000000000000776,,32118641,cc-by-nc-nd,,2020,"Chen, Ze-Liang; Zhang, Wen-Jun; Lu, Yi; Guo, Cheng; Guo, Zhong-Min; Liao, Cong-Hui; Zhang, Xi; Zhang, Yi; Han, Xiao-Hu; Li, Qian-Lin; Lu, Jia-Hai",Chin Med J (Engl),3002084665,#3435,True
e4b23ec957446463f8d7be44f3ddbbf6155ae10c,CZI,Single-cell RNA sequencing data suggest a role for angiotensin-converting enzyme 2 in kidney impairment in patients infected with 2019-nCoV,10.1097/CM9.0000000000000783,,32118645,cc-by-nc-nd,,2020,"Deng, Yi-Yao; Zheng, Ying; Cai, Guang-Yan; Chen, Xiang-Mei; Hong, Quan",Chin Med J (Engl),2794521141,#3423,True
69ca8c0a79935fbe985f02fc53c1a9da5c42acd3,CZI,Effect of isolation practice on the transmission of middle east respiratory syndrome coronavirus among hemodialysis patients: A 2-year prospective cohort study,10.1097/MD.0000000000018782,,32011472,cc-by-nc-nd,"Hemodialysis (HD) patients had a high rate of infection transmission and mortality during the middle east respiratory syndrome coronavirus (MERS-CoV) outbreak in Saudi Arabia. A standardized guideline on isolation technique for exposed HD patients is not available. Thus, this study aimed to evaluate the effect of different isolation strategies on the prevention of secondary viral transmission and clinical outcomes among exposed HD patients.During the 2015 MERS-CoV outbreak in Korea, 116 patients in 3 HD units were incidentally exposed to individuals with confirmed MERS-CoV infection and underwent different types of isolation, which were as follows: single-room isolation (n = 54, 47%), cohort isolation (n = 46, 40%), and self-imposed quarantine (n = 16, 13%). The primary outcome was rate of secondary viral transmission. The secondary outcome measures were changes in clinical and biochemical markers during the isolation period, difference in clinical and biochemical markers according to the types of isolation practice, and effect of isolation practice on patient survival.During a mean isolation period of 15 days, no further cases of secondary transmission were detected among HD patients. Plasma hemoglobin, serum calcium, and serum albumin levels and single-pool Kt/V decreased during the isolation period but normalized thereafter. Patients who were subjected to self-imposed quarantine had higher systolic and diastolic blood pressure, lower total cholesterol level, and lower Kt/V than those who underwent single-room or cohort isolation. During the 24-month follow-up period, 12 patients died. However, none of the deaths occurred during the isolation period, and no differences were observed in patient survival rate according to different isolation strategies.Although 116 participants in 3 HD units were incidentally exposed to MERS-CoV during the 2015 outbreak in Korea, strict patient surveillance and proper isolation practice prevented secondary transmission of the virus. Thus, a renal disaster protocol, which includes proper contact surveillance and isolation practice, must be established in the future to accommodate the needs of HD patients during disasters or outbreaks.",2020,"Park, Hayne Cho; Lee, Sang-Ho; Kim, Juhee; Kim, Do Hyoung; Cho, AJin; Jeon, Hee Jung; Oh, Jieun; Noh, Jung-Woo; Jeong, Da-Wun; Kim, Yang-Gyun; Lee, Chang-Hee; Yoo, Kyung Don; Lee, Young-Ki",Medicine (Baltimore),3000673943,#287,True
5ba8056230c17ec133169d79aacf61ed7d4b458b,CZI,"The novel coronavirus outbreak in Wuhan, China",10.1186/s41256-020-00135-6,,,cc-by,"The novel coronavirus (2019-nCoV, or COVID-19) epidemic first broke out in Wuhan and has been spreading in whole China and the world. The numbers of new infections and deaths in Wuhan are still increasing, which have posed major public health and governance concerns. A series of mandatory actions have been taken by the municipal and provincial governments supported by the central government, such as measures to restrict travels across cities, case detection and contact tracing, quarantine, guidance and information to the public, detection kit development, etc. Challenges such as lacking effective drugs, insufficient hospital services and medical supplies, logistics, etc. have much alleviated with the solidarity of the whole society. The pandemic will definitely be ended with the continuous efforts of both national and international multi-sectoral bodies.",2020,"Zhu, Hengbo; Wei, Li; Niu, Ping",Global Health Research and Policy,2023898906,#3037,True
861f05718b673306c2044167d92bb31d68a0d9bb,CZI,Tracking online heroisation and blame in epidemics,10.1016/S2468-2667(20)30033-5,,,cc-by,,2020,"Atlani-Duault, Laëtitia; Ward, Jeremy K.; Roy, Melissa; Morin, Céline; Wilson, Andrew",The Lancet Public Health,2804996859,#3217,True
66b67940ae16f657fd93fad230081d20d98c55f7,CZI,A precision medicine approach to managing Wuhan Coronavirus pneumonia,10.1093/pcmedi/pbaa002,,,cc-by-nc,"In December, 2019, several patients with pneumonia of an unknown cause were detected in Wuhan, China. On January 7, 2020, the causal organism was identified as a new coronavirus, later named as the “2019 novel coronavirus” (2019-nCoV). Genome sequencing found the genetic sequence of 2019-nCoV homologous to that of Severe Acute Respiratory Syndrome-Associated Coronavirus (SARS-CoV). As of January 29, 2020, the virus had been diagnosed in more than 7,000 patients in China and 77 outside this country. It is reported that both symptomatic and asymptomatic patients with 2019-nCov can play a role in disease transmission via airborne and contact. This finding has caused a great concern about the prevention of illness spread. The clinical features of the infection are not specific and are often indistinguishable from those of other respiratory infections, making it difficult to diagnose. Given that the virus has a strong ability to spread between individuals, it is of top priority to identify potential or suspected patients as soon as possible. Or the virus may cause a serious pandemic. Therefore, a precision medicine approach to managing this disease is urgently needed for detecting and controlling the spread of the virus. In this article, we present such an approach to managing 2019-nCoV-related pneumonia based on the unique traits of the virus recently revealed, and on our experience with coronaviruses at West China Hospital in Chengdu, China.",2020,"Minjin Wang, Yanbing Zhou, Zhiyong Zong, Zongan Liang, Yu Cao, Hong Tang, Bin Song, Zixing Huang, Yan Kang, Ping Feng, Binwu Ying, Weimin Li",Precision Clinical Medicine,3006495046,#262,True
d666c86af7eeaee9a830f99d863045f52571ea5f,CZI,"Extracorporeal membrane oxygenation support in 2019 novel coronavirus disease: indications, timing, and implementation",10.1097/CM9.0000000000000778,,32118643,cc-by-nc-nd,,2020,"Li, Min; Gu, Si-Chao; Wu, Xiao-Jing; Xia, Jin-Gen; Zhang, Yi; Zhan, Qing-Yuan",Chin Med J (Engl),3005079553,#3360,True
b25291591ed2b529efff2b281c7be556950a256b,CZI,Editor's Note,10.14789/jmj.2020.66.1-en,,,cc-by,"A few years ago, when I wrote an editorial note, there was an unseasonable heavy snowfall,making the city of Tokyo havoc. This time the cause is the 2019 Novel Coronavirus (SARS-CoV-2).Infection by this novel virus had become grave news involving the whole world by the end ofJanuary. Now, as I am writing this, there is no cure, and the number of patients is also increasingday by day in Japan. Masks are out of stock throughout the city, and I have heard that people queueup for few masks in front of drug stores from early in the morning.The effectiveness of wearing a mask to prevent infection is limited. What is the cause of such asituation? As a matter of fact, in an epidemic of infection, the most serious problem is not infectionitself, but unscientific rumors and people who are easily swayed by them. Avoidance of vaccinationby insisting that vaccines have no effect or that they are harmful to the body is fundamentally thesame. The anti-vaccination movement still exists despite the evidence-based medicine, and thereare concerns about its expansion. However, even with scientific evidence, it is not easy to persuadeanti-vaccinationists, and this is the moment, when we, academia, feel powerless.Nevertheless, we should not be discouraged. The mission of academia is to conduct reliableresearch. Reliable data are obtained from such research, and scientific solution of the problemssteadily proceed. Based on the outcomes of these data and solutions, scientists themselves shouldcreate the methods of advocacy and persuasion or rely on experts in this area.However, scientists should solve the problems with science. Academic journals such as theJuntendo Medical Journal may be of marked significance in this regard. It is important to get theexcellent findings, but even negative data need to be published somewhere and shared amongvarious people, whenever they lead to academically important questions. Such data promote thediscussions, deeper research perspectives, and new themes. Submitting articles in English has beenestablished in the Juntendo Medical Journal. The journal will achieve further progress in the nearfuture.Toshihiro MitaDepartment of Tropical Medicine and ParasitologyCall for feature article proposalsTo introduce the latest medical findings, Juntendo Medical Journal features a specific focus areafor each issue. We would like to request all our readers to address any suggestions or proposals forsuitable focus areas to our editorial office.",2020,,Juntendo Medical Journal,2887248870,#3229,False
140e6d0298bfcd1e825a4b81dcabc50d1658357a,CZI,The Novel Coronavirus: A Bird's Eye View,10.15171/ijoem.2020.1921,,32020915,cc-by-nc-sa,"The novel coronavirus (2019-nCoV) outbreak, which initially began in China, has spread to many countries around the globe, with the number of confirmed cases increasing every day. With a death toll exceeding that of the SARS-CoV outbreak back in 2002 and 2003 in China, 2019-nCoV has led to a public health emergency of international concern, putting all health organizations on high alert. Herein, we present on an overview of the currently available information on the pathogenesis, epidemiology, clinical presentation, diagnosis, and treatment of this virus.",2020,"Habibzadeh, Parham; Stoneman, Emily K.",Int J Occup Environ Med,3004735879,#319,True
2aff265697682af71816737a2fd85f1d9bc9a0c4,CZI,The Rate of Underascertainment of Novel Coronavirus (2019-nCoV) Infection: Estimation Using Japanese Passengers Data on Evacuation Flights,10.3390/jcm9020419,,32033064,cc-by,"From 29 to 31 January 2020, a total of 565 Japanese citizens were evacuated from Wuhan, China on three chartered flights. All passengers were screened upon arrival in Japan for symptoms consistent with novel coronavirus (2019-nCoV) infection and tested for presence of the virus. Assuming that the mean detection window of the virus can be informed by the mean serial interval (estimated at 7.5 days), the ascertainment rate of infection was estimated at 9.2% (95% confidence interval: 5.0, 20.0). This indicates that the incidence of infection in Wuhan can be estimated at 20,767 infected individuals, including those with asymptomatic and mildly symptomatic infections. The infection fatality risk (IFR)-the actual risk of death among all infected individuals-is therefore 0.3% to 0.6%, which may be comparable to Asian influenza pandemic of 1957-1958.",2020,"Nishiura, Hiroshi; Kobayashi, Tetsuro; Yang, Yichi; Hayashi, Katsuma; Miyama, Takeshi; Kinoshita, Ryo; Linton, Natalie M.; Jung, Sung-Mok; Yuan, Baoyin; Suzuki, Ayako; Akhmetzhanov, Andrei R.",J Clin Med,3004658686,#536,True
,CZI,"Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, Shenzhen, China, 2020",10.3201/eid2606.200239,,32125269,cc-by,"Since early January 2020, after the outbreak of 2019 novel coronavirus infection in Wuhan, China, ≈365 confirmed cases have been reported in Shenzhen, China. The mode of community and intrafamily transmission is threatening residents in Shenzhen. Strategies to strengthen prevention and interruption of these transmissions should be urgently addressed.",2020,"Liu, Jiaye; Liao, Xuejiao; Qian, Shen; Yuan, Jing; Wang, Fuxiang; Liu, Yingxia; Wang, Zhaoqin; Wang, Fu-Sheng; Liu, Lei; Zhang, Zheng",Emerg Infect Dis,2116732940,#3346,
,CZI,Risk for Transportation of 2019 Novel Coronavirus Disease from Wuhan to Other Cities in China,10.3201/eid2605.200146,,32053479,cc-by,"On January 23, 2020, China quarantined Wuhan to contain 2019 novel coronavirus disease (COVID-19). We estimated the probability of transportation of COVID-19 from Wuhan to 369 other cities in China before the quarantine. Expected COVID-19 risk is >50% in 130 (95% CI 89-190) cities and >99% in the 4 largest metropolitan areas.",2020,"Du, Zhanwei; Wang, Lin; Cauchemez, Simon; Xu, Xiaoke; Wang, Xianwen; Cowling, Benjamin J.; Meyers, Lauren Ancel",Emerg Infect Dis,3006320625,#872,
,CZI,Latest assessment on COVID-19 from the European Centre for Disease Prevention and Control (ECDC),10.2807/1560-7917.ES.2020.25.8.2002271,,,cc-by,,2020,"team, Eurosurveillance editorial",Eurosurveillance,,#2535,
,CZI,"COVID-19 in 2 Persons with Mild Upper Respiratory Symptoms on a Cruise Ship, Japan",10.3201/eid2606.200452,,32118533,cc-by,"We describe 2 cases of COVID-19 in patients with mild upper respiratory symptoms. Both patients worked on a cruise ship quarantined off the coast of Japan. One patient had persistent, low-grade upper respiratory tract symptoms without fever. The other patient had rapid symptom cessation but persistent viral RNA detection.",2020,"Arashiro, Takeshi; Furukawa, Keiichi; Nakamura, Akira",Emerging infectious diseases,2108857951,#3520,
,CZI,"Potential Presymptomatic Transmission of SARS-CoV-2, Zhejiang Province, China, 2020",10.3201/eid2605.200198,,32091386,cc-by,"We report a 2-family cluster of persons infected with severe acute respiratory syndrome coronavirus 2 in the city of Zhoushan, Zhejiang Province, China, during January 2020. The infections resulted from contact with an infected but potentially presymptomatic traveler from the city of Wuhan in Hubei Province.",2020,"Tong, Zhen-Dong; Tang, An; Li, Ke-Feng; Li, Peng; Wang, Hong-Ling; Yi, Jing-Ping; Zhang, Yong-Li; Yan, Jian-Bo",Emerg Infect Dis,3006655826,#1754,
,CZI,Ten hot issues of breast cancer under the novel coronavirus,10.0376/cma.j.issn.0376-2491.2020.0002,,32036640,,,2020,"Jiang, Z. F.; Li, J. B.",Zhonghua Yi Xue Za Zhi,3003451419,#615,
,CZI,Coronavirus Infections-More Than Just the Common Cold,10.1001/jama.2020.0757,,,,,2020,"Paules, C. I.; Marston, H. D.; Fauci, A. S.",JAMA - Journal of the American Medical Association,3000834295,#146,
,CZI,"The Novel Coronavirus Originating in Wuhan, China: Challenges for Global Health Governance",10.1001/jama.2020.1097,,31999307,,,2020,"Phelan, A. L.; Katz, R.; Gostin, L. O.",Jama,3003749070,#87,
,CZI,2019 Novel Coronavirus—Important Information for Clinicians,10.1001/jama.2020.1490,,,,"In early December 2019 a patient was diagnosed with an unusual pneumonia in the city of Wuhan, China. By December 31 the World Health Organization (WHO) regional office in Beijing had received notification of a cluster of patients with pneumonia of unknown cause from the same city. Wuhan, the capital city of Hubei Province in central China, is the nation’s seventh largest city, with a population of 11 million people. Over the next few days, researchers at the Wuhan Institute of Virology performed metagenomics analysis using next-generation sequencing from a sample collected from a bronchoalveolar lavage and identified a novel coronavirus as the potential etiology. They called it novel coronavirus 2019 (nCoV-2019). The US Centers for Disease Control and Prevention (CDC) refers to it as 2019 novel coronavirus (2019-nCoV).",2020,"del Rio, Carlos; Malani, Preeti N.",JAMA,,#329,
,CZI,"Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China",10.1001/jama.2020.1585,,32031570,,"IMPORTANCE: In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. OBJECTIVE: To describe the epidemiological and clinical characteristics of NCIP. DESIGN, SETTING, AND PARTICIPANTS: Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. EXPOSURES: Documented NCIP. MAIN OUTCOMES AND MEASURES: Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. RESULTS: Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). CONCLUSIONS AND RELEVANCE: In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.",2020,"Wang, Dawei; Hu, Bo; Hu, Chang; Zhu, Fangfang; Liu, Xing; Zhang, Jing; Wang, Binbin; Xiang, Hui; Cheng, Zhenshun; Xiong, Yong; Zhao, Yan; Li, Yirong; Wang, Xinghuan; Peng, Zhiyong",JAMA,3005079553,#537,
,CZI,Clinical characteristics of 28 patients with novel coronavirus pneumonia,10.1001/jama.2020.1585,,,,"Objective To analysis the clinical characteristics and experiences in diagnosis and treatment of the patients with novel coronavirus pneumonia (NCP). Methods Clinical data of 28 patients with NCP in Nanning Fourth People's Hospital from January 22 to February 5 in 2020 were collected. The clinical manifestations, epidemiological history, laboratory tests, imaging examinations and treatments of patients were analyzed retrospectively. Results The 28 patients with confirmed viral pneumonia included 11 males and 17 females, ranging from 11 to 68 years. They all had history of epidemiological exposure and were all positive for 2019-nCoV nucleic acid in throat swabs. There were one mild case, 25 ordinary cases and two severe cases. There were four groups of family clusters. The illness onset ranged from 1 to 12 days after exposure, and the time from the symptom onset to the positive result of the nucleic acid test was 0 to 13 days. The clinical symptoms were mainly fever and cough, which progressed rapidly in a short period of time. Since the onset of illness, the peak values of axillary temperature of the 28 patients were 36.6~39.5 ℃, while five patients had no fever throughout the course of the disease with the peak temperature of ≤37 ℃. There were two patients presented with decreased white blood cell counts, five patients with elevated C reactive protein, six patients with abnormal alanine aminotransferase, three patients with abnormal aspartate aminotransferase,10 patients with elevated creatine kinase, three patients with elevated creatine kinase isoenzyme, four patients with elevated lactate dehydrogenase, and all with normal procalcitonin levels. The chest computed tomography examinations showed that the common features were ground glass shadows (21 cases), blurred edges (18 cases), speckles and patchy shadows (17 cases), thickening and disorder of some lung textures (7 cases), and visible band shadows (7 cases). Pulmonary lesions often progressed rapidly. One 11-year-old child was treated with alpha-interferon alone, and 27 patients were treated with alpha-interferon inhalation plus lopinavir/ritonavir with 4 withdrawal due to adverse reactions. Up to February 12, nine patients had been discharged from the hospital, who were ordinary cases, without death cases. Conclusions The NCP patients mostly present with fever and cough. Pulmonary lesions often progress rapidly. Respiratory pathogen testing should be conducted as early as possible and repeatedly. Disisolation should be cautious for suspected people who are negative for 2019-nCoV nucleic acid in pharynx swabs.",2020,"ZHAO, Rui; LIANG, Yunguang; LIN, Yanrong; LU, Ning; LI, Qiulian; LI, Youling; PAN, Pan; HE, Wei",Chinese Journal of Infectious Diseases,3005079553,#2054,
,CZI,"Manifestations of Digestive system in hospitalized patients with novel coronavirus pneumonia in Wuhan, China: a single-center, descriptive study",10.1001/jama.2020.1585,,,,"Objective To study the manifestations of digestive system of hospitalized patients with novel coronavirus pneumonia (NCP) in Wuhan, China, and to provide reference for disease control and treatment. Methods The data of hospitalized patients with NCP in the Sino-French Branch of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology was retrospectively analyzed, which included general information, nucleic acid test, severity degree of disease, incubation period, initial symptoms and manifestations of digestive system. The general information, positive rate of nucleic acid detection, and manifestations of digestive system were compared between critical patients who required non-invasive or invasive assisted ventilation (critical group) and non-critical patients without assisted ventilation (non-critical group). Continuous corrected chi-square test and independent sample median test were performed for statistical analysis. Results Among the 305 patients there were 146 males (47.9%) and 159 females (52.1%), median age 57 years old. Nucleic acid assay of nasopharynx swab or pharynx swab of 84.1% (228/271) patients were positive. Forty-six patients (15.1%) were in critical group and 259 patients (84.9%) were in non-critical group. The incubation period was one to fifteen days, and the median period was six days. The initial symptoms mainly were fever (81.1%, 163/201), cough (39.3%, 79/201), fatigue (54.7%, 110/201), and loss of appetite (50.2%, 101/201). In one to ten days after the disease onset, 79.1% (159/201) of patients developed gastrointestinal symptoms including nausea (29.4%, 59/201), vomiting (15.9%, 32/201), or abdominal pain (6.0%, 12/201). 49.5% (146/295) of patients had diarrhea, median time was 3.3 days, (3.3±1.6) times per day, and a duration of (4.1±2.5) days. Excluding possible drug-related diarrhea, the incidence of diarrhea still was 22.2%. Only 6.9% (4/58) of patients were found leukocytes or fecal occult blood positive in regular stool test. ALT, AST, or bilirubin increased in 39.1% (119/304) of patients at admission. Patients with ALT or AST ≥ 80 U/L only accounted for 7.9% (24/304) and 6.3% (19/304), respectively. About 2.0% (6/304) of patients also had increased bilirubin level, average level was (37.4 ± 21.1) μmol/L. The median age of critical group was older than that of non-critical group (65.5 years vs. 56 years), at admission the rates of abnormal liver function test abnormal and slightly increased AST (40~80 U/L) of critical group were both higher than those of non-critical group (67.4% (31/46) vs. 34.1% (88/258) and 47.8% (22/46) vs. 21.7% (56/228)), and the differences were statistically significant ( x 2 =5.885, 18.154 and 15.723;all P <0.05). There were no statistically significant differences in the proportion of male (58.7% (27/46) vs. 45.9% (119/259)), the positive rate of nucleic acid detection (94.6% (35/37) vs. 82.5% (193/234)), the percentage of patients with gastrointestinal symptoms (85.0% (17/20) vs. 78.5% (142/181)), the rate of diarrhea (44.7% (17/38)vs. 50.2% (129/257)) and ratio of patients with abnormal bilirubin level (6.5% (3/46) vs. 1.2% (3/258)) (all P >0.05). Conclusions The manifestation of digestive system of hospitalized NCP patients in Wuhan is significant, the ratio of patients with diarrhea and abnormal aminotransferase level is high. And at admission the rate of patients with abnormal liver function rate of critical group is higher than that of non-critical group, which will provide reference for the prevention and treatment of NCP.",2020,"FANG, Dan; MA, Jingdong; GUAN, Jialun; WANG, Muru; SONG, Yang; TIAN, Dean; LI, Peiyuan",Chinese Journal of Digestion,3005079553,#2296,
,CZI,Analysis of clinical characteristics of new coronavirus pneumonia patients in secondary epidemic areas,10.1001/jama.2020.1585,,,,"Objective Understand the clinical characteristics of confirmed pneumonia patients infected with new corona virus in secondary epidemic areas and guide the diagnosis and treatment of novel pneumonia in secondary epidemic areas and provide a reference for clinical prevention and control of the epidemic situation. Methods The clinical data of 33 patients admitted with pneumonia caused by a novel coronavirus in the Second Affiliated Hospital of Wenzhou Medical University from January 15 to February 1, 2020, were retrospectively reviewed. At the onset of the disease, we analyzed the primary symptoms such as fever, cough, fatigue, chest tightness, chest pain and also a significant blood test results of the patients. According to the patient's contact history, it was divided into the direct infection group of the main epidemic area and the indirect contact infection group of the main epidemic areas. The difference between clinical manifestations among the two groups was analyzed. Results The main clinical symptoms of patients with novel coronavirus pneumonia in the secondary epidemic area were respiratory tract and systemic symptoms. After grouping according to the presence and absence of direct contact in the main epidemic area, there was no significant difference in baseline data between the two groups, and there was no significant difference in symptoms and signs between the two groups ( P < 0.05). Some patients had serum amyloid protein (SAP) increased abnormall. Conclusions The respiratory tract and systemic symptoms are the primary symptoms of the patients with the new type of coronavirus pneumonia in the secondary epidemic area, which are not typical. The abnormal increase of serum amyloid protein (SAA) may be used as an auxiliary index for diagnosis and treatment.",2020,"JI, Weiping; CHEN, Xinxin; XU, Hui; JIN, Chenci; HU, Yunming; JI, Chengyuan; SHEN, Xian",Chinese Critical Care Medicine,3005079553,#2247,
,CZI,"Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China",10.1001/jama.2020.1623,,32031568,,,2020,"Chang, De; Lin, Minggui; Wei, Lai; Xie, Lixin; Zhu, Guangfa; Dela Cruz, Charles S.; Sharma, Lokesh",JAMA,3005347918,#538,
,CZI,Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus: Lessons From Previous Epidemics,10.1001/jama.2020.1960,,32044915,,,2020,"Swerdlow, David L.; Finelli, Lyn",JAMA,3005637261,#646,
,CZI,US Emergency Legal Responses to Novel Coronavirus: Balancing Public Health and Civil Liberties,10.1001/jama.2020.2025,,,,"With increasing numbers of cases of coronavirus disease 2019 (COVID-19) globally and in the United States, Health and Human Services (HHS) Secretary Alex Azar declared a national public health emergency on January 31. The emergency declaration of the HHS authorizes additional resources, enhanced federal powers, interjurisdictional coordination, and waivers of specific regulations. State and local public health emergency declarations are also likely. During crises, government has a special responsibility to thoughtfully balance public health protections and civil liberties.",2020,"Gostin, Lawrence O.; Hodge, James G., Jr.",JAMA,3006598047,#859,
,CZI,Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China,10.1001/jama.2020.2131,,,,"Previous studies suggest that COVID-19 is more likely to infect older adult men, particularly those with chronic comorbidities.2-4 Few infections in children have been reported. We identified all infected infants in China and described demographic, epidemiologic, and clinical features.",2020,"Wei, Min Yuan, Jingping Liu,Yu Fu,Tao Yu,Xue Zhang,Zhi-Jiang",JAMA,3006490857,#884,
,CZI,Preparing for the Most Critically Ill Patients With COVID-19: The Potential Role of Extracorporeal Membrane Oxygenation,10.1001/jama.2020.2342,,32074258,,,2020,"MacLaren, Graeme; Fisher, Dale; Brodie, Daniel",JAMA,1908342561,#1551,
,CZI,COVID-19 in Singapore—Current Experience: Critical Global Issues That Require Attention and Action,10.1001/jama.2020.2467,,,,"On December 31, 2019, China informed the World Health Organization of a novel viral pneumonia in the city of Wuhan, in Hubei Province. Singapore is an independent city-state 3400 km (2125 miles) from Wuhan, but as a major air hub had an average of 330 000 visitor arrivals from China each month in 2019. On January 2, 2020, Singapore’s Ministry of Health alerted all physicians to identify any patient with pneumonia and a recent travel history to Wuhan. On January 3, Singapore started temperature screening at its airport of all travelers arriving from Wuhan. Researchers in China identified a novel coronavirus as the causative agent on January 9, the genetic sequence was released on January 12, and human transmission to health care workers was confirmed on January 20.",2020,"Wong, John E. L.; Leo, Yee Sin; Tan, Chorh Chuan",JAMA,,#1353,
,CZI,Presumed Asymptomatic Carrier Transmission of COVID-19,10.1001/jama.2020.2565,,32083643,,,2020,"Bai, Yan; Yao, Lingsheng; Wei, Tao; Tian, Fei; Jin, Dong-Yan; Chen, Lijuan; Wang, Meiyun",JAMA,2041408682,#1696,
,CZI,Coronavirus Disease 2019 and Influenza,10.1001/jama.2020.2633,,32101254,,,2020,"Livingston, Edward; Bucher, Karen; Rekito, Andrew",Jama,3006364226,#3805,
,CZI,Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention,10.1001/jama.2020.2648,,32091533,,,2020,"Wu, Zunyou; McGoogan, Jennifer M.",JAMA,,#1741,
,CZI,Positive RT-PCR Test Results in Patients Recovered From COVID-19,10.1001/jama.2020.2783,,32105304,,,2020,"Lan, L.; Xu, D.; Ye, G.; Xia, C.; Wang, S.; Li, Y.; Xu, H.",Jama,1980645084,#2865,
,CZI,COVID-19—New Insights on a Rapidly Changing Epidemic,10.1001/jama.2020.3072,,,,"Since first reported in Wuhan, China, in late December 2019, the outbreak of the novel coronavirus now known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has spread globally. As of February 27, 2020, more than 82 000 cases of coronavirus disease 2019 (COVID-19) (the disease caused by SARS-CoV-2) and 2800 deaths have been reported, of which approximately 95% of cases and 97% of deaths are in China. Cases have now been reported in 49 other countries. A particularly large outbreak occurred among the passengers and crew of the Diamond Princess cruise ship, where more than 700 infections are reported.",2020,"del Rio, Carlos; Malani, Preeti N.",JAMA,,#2788,
,CZI,"Response to COVID-19 in Taiwan: Big Data Analytics, New Technology, and Proactive Testing",10.1001/jama.2020.3151,,32125371,,"Taiwan is 81 miles off the coast of mainland China and was expected to have the second highest number of cases of coronavirus disease 2019 (COVID-19) due to its proximity to and number of flights between China.1 The country has 23 million citizens of which 850 000 reside in and 404 000 work in China.2,3 In 2019, 2.71 million visitors from the mainland traveled to Taiwan.4 As such, Taiwan has been on constant alert and ready to act on epidemics arising from China ever since the severe acute respiratory syndrome (SARS) epidemic in 2003. Given the continual spread of COVID-19 around the world, understanding the action items that were implemented quickly in Taiwan and assessing the effectiveness of these actions in preventing a large-scale epidemic may be instructive for other countries. COVID-19 occurred just before the Lunar New Year during which time millions of Chinese and Taiwanese were expected to travel for the holidays. Taiwan quickly mobilized and instituted specific approaches for case identification, containment, and resource allocation to protect the public health. Taiwan leveraged its national health insurance database and integrated it with its immigration and customs database to begin the creation of big data for analytics; it generated real-time alerts during a clinical visit based on travel history and clinical symptoms to aid case identification. It also used new technology, including QR code scanning and online reporting of travel history and health symptoms to classify travelers’ infectious risks based on flight origin and travel history in the past 14 days. Persons with low risk (no travel to level 3 alert areas) were sent a health declaration border pass via SMS (short message service) messaging to their phones for faster immigration clearance; those with higher risk (recent travel to level 3 alert areas) were quarantined at home and tracked through their mobile phone to ensure that they remained at home during the incubation period. Moreover, Taiwan enhanced COVID-19 case finding by proactively seeking out patients with severe respiratory symptoms (based on information from the National Health Insurance [NHI] database) who had tested negative for influenza and retested them for COVID-19; 1 was found of 113 cases. The toll-free number 1922 served as a hotline for citizens to report suspicious symptoms or cases in themselves or others; as the disease progressed, this hotline has reached full capacity, so each major city was asked to create its own hotline as an alternative. It is not known how often this hotline has been used. The government addressed the issue of disease stigma and compassion for those affected by providing food, frequent health checks, and encouragement for those under quarantine. This rapid response included hundreds of action items (eTable in the Supplement).",2020,"Wang, C. Jason; Ng, Chun Y.; Brook, Robert H.",JAMA,2157954477,#3284,
,CZI,Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore,10.1001/jama.2020.3204,,,,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China.To report the initial experience in Singapore with the epidemiologic investigation of this outbreak, clinical features, and management.Descriptive case series of the first 18 patients diagnosed with polymerase chain reaction (PCR)–confirmed SARS-CoV-2 infection at 4 hospitals in Singapore from January 23 to February 3, 2020; final follow-up date was February 25, 2020.Confirmed SARS-CoV-2 infection.Clinical, laboratory, and radiologic data were collected, including PCR cycle threshold values from nasopharyngeal swabs and viral shedding in blood, urine, and stool. Clinical course was summarized, including requirement for supplemental oxygen and intensive care and use of empirical treatment with lopinavir-ritonavir.Among the 18 hospitalized patients with PCR-confirmed SARS-CoV-2 infection (median age, 47 years; 9 [50%] women), clinical presentation was an upper respiratory tract infection in 12 (67%), and viral shedding from the nasopharynx was prolonged for 7 days or longer among 15 (83%). Six individuals (33%) required supplemental oxygen; of these, 2 required intensive care. There were no deaths. Virus was detectable in the stool (4/8 [50%]) and blood (1/12 [8%]) by PCR but not in urine. Five individuals requiring supplemental oxygen were treated with lopinavir-ritonavir. For 3 of the 5 patients, fever resolved and supplemental oxygen requirement was reduced within 3 days, whereas 2 deteriorated with progressive respiratory failure. Four of the 5 patients treated with lopinavir-ritonavir developed nausea, vomiting, and/or diarrhea, and 3 developed abnormal liver function test results.Among the first 18 patients diagnosed with SARS-CoV-2 infection in Singapore, clinical presentation was frequently a mild respiratory tract infection. Some patients required supplemental oxygen and had variable clinical outcomes following treatment with an antiretroviral agent.",2020,"Young, Barnaby Edward; Ong, Sean Wei Xiang; Kalimuddin, Shirin; Low, Jenny G.; Tan, Seow Yen; Loh, Jiashen; Ng, Oon-Tek; Marimuthu, Kalisvar; Ang, Li Wei; Mak, Tze Minn; Lau, Sok Kiang; Anderson, Danielle E.; Chan, Kian Sing; Tan, Thean Yen; Ng, Tong Yong; Cui, Lin; Said, Zubaidah; Kurupatham, Lalitha; Chen, Mark I. Cheng; Chan, Monica; Vasoo, Shawn; Wang, Lin-Fa; Tan, Boon Huan; Lin, Raymond Tzer Pin; Lee, Vernon Jian Ming; Leo, Yee-Sin; Lye, David Chien; for the Singapore Novel Coronavirus Outbreak Research, Team",JAMA,2156226164,#3256,
,CZI,"Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From a Symptomatic Patient",10.1001/jama.2020.3227,,,,"Coronaviruses have been implicated in nosocomial outbreaks with environmental contamination as a route of transmission. Similarly, nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported. However, the mode of transmission and extent of environmental contamination are unknown.",2020,"Ong, Sean Wei Xiang; Tan, Yian Kim; Chia, Po Ying; Lee, Tau Hong; Ng, Oon Tek; Wong, Michelle Su Yen; Marimuthu, Kalisvar",JAMA,2968894028,#3868,
,CZI,Priorities for the US Health Community Responding to COVID-19,10.1001/jama.2020.3413,,32125355,,,2020,"Adalja, Amesh A.; Toner, Eric; Inglesby, Thomas V.",JAMA,3006304371,#3467,
,CZI,"To ease anxiety over coronavirus, leaders prescribe dose of common sense",10.1002/adaw.32649,,,,Wash hands thoroughly.,2020,"Enos, Gary",Alcoholism & Drug Abuse Weekly,2052183476,#5199,
,CZI,Hematologic parameters in patients with COVID-19 infection,10.1002/ajh.25774,,32129508,,,2020,"Fan, Bingwen Eugene; Chong, Vanessa Cui Lian; Chan, Stephrene Seok Wei; Lim, Gek Hsiang; Lim, Kian Guan Eric; Tan, Guat Bee; Mucheli, Sharavan Sadasiv; Kuperan, Ponnudurai; Ong, Kiat Hoe",Am J Hematol,2600109316,#4086,
,CZI,Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV,10.1002/cbic.202000047,,,,"With the current trajectory of the 2019-nCoV outbreak unknown, public health and medicinal measures will both be needed to contain spreading of the virus and to optimize patient outcomes. Although little is known about the virus, an examination of the genome sequence shows strong homology with its better-studied cousin, SARS-CoV. The spike protein used for host cell infection shows key nonsynonymous mutations that might hamper the efficacy of previously developed therapeutics but remains a viable target for the development of biologics and macrocyclic peptides. Other key drug targets, including RNA-dependent RNA polymerase and coronavirus main proteinase (3CLpro), share a strikingly high (>95 %) homology to SARS-CoV. Herein, we suggest four potential drug candidates (an ACE2-based peptide, remdesivir, 3CLpro-1 and a novel vinylsulfone protease inhibitor) that could be used to treat patients suffering with the 2019-nCoV. We also summarize previous efforts into drugging these targets and hope to help in the development of broad-spectrum anti-coronaviral agents for future epidemics.",2020,"Morse, J. S.; Lalonde, T.; Xu, S.; Liu, W. R.",ChemBioChem,3005527412,#3842,
,CZI,News,10.1002/cind.842_3.x,,,,"Chinese scientists released genetic information on the coronavirus causing an outbreak of SARS-like illness in Wuhan, China. The Vaccine Research Institute at the US National Institutes of Health (NIH) immediately began development of a new vaccine. After the 2003 SARS outbreak, it took 20 months from the release of the viral genome to get a vaccine ready for human trials. The zika virus took six months. Now, the NIH is pushing to have a vaccine ready for testing in three to six months. The race is on. The NIH team took the template for a SARS vaccine and swapped enough code from the new virus to start a new vaccine. Researchers, having experience with SARS, already knew which part of the virus to choose for the vaccine’s antigen, a sort of red flag for the immune system. This synthetic antigen will prod the body to make antibodies.",2020,,Chemistry & Industry,2973850158,#2705,
,CZI,"Machine Learning, COVID-19 (2019-nCoV), and multi-OMICS",10.1002/cyto.a.23990,,,,"The primary plan of my editorial for this month was to highlight and comment on the special issue of this month: “Machine Learning for Single Cell Data”. I wish to emphasize and thank the Guest Editors of this special issue, Yvan Saeys and Greg Finak, for their outstanding success and hard work to assemble excellent manuscripts for this issue. I am referring to their guest editorial giving you more details on aims and scopes and elaborating on specific articles. I started drafting this editorial while attending the annual Photonics West conference in San Francisco, presumably the largest showcase on photonics technologies and instrumentation. Scientifically, the sub‐conference BIOS demonstrated the broadness and vividness of photonics technologies in life sciences and particularly in single cell analysis. When searching for relevant literature for this editorial, I was also tracking the actual global developments. This brought me to change my focus and comment on some issues that are relevant to our field and somewhat related to that of the special issue. First of all, Nature Methods announced their Method of the Year 2019 1. It is: “Single‐cell multimodal omics” and acknowledges (among others) the important contribution of highly multiplexed flow cytometry and cell sorting to the increased understanding of single cell biology and cell systems. This is motivating and confirms that cytometry is receiving the focus of attention. Concurrently, in the last weeks the relevance of the recent COVID‐19 (2019‐nCoV) outbreak and its effects started to become evident as everybody was monitoring the number of cases registered globally 2. As conference chairs, we were facing the fact that many of our speakers and colleagues became unavailable. Not only that, but the eeriness of the infection (it is transmissible already during its asymptomatic latency period of up to two weeks, recent results indicate even longer) gave many attendees an uneasy feeling. This brings me to two points worth discussing. (a) Are large scale conferences with global attendance still state of the art or should they be rethought; and (b) to what extent can cytometry support global efforts in various fields of epidemic outbreaks of infectious diseases? In the past one to two decades the world faced several outbreaks of different viral infections that were luckily not as disastrous as initially anticipated but still claimed victims. These were coronaviruses such as the Severe Acute Respiratory Syndrome coronavirus (SARS‐CoV) in 2002/2003, the Middle East Respiratory Syndrome coronavirus (MERS‐CoV) with occasional outbreaks since 2012 or influenza viruses like the H1N1 pandemic in 2009/2010. It is only a matter of time until other pandemics follow. Global travel for work and leisure supports viral spread and can transport the infection to nearly all places of the globe within days. Global conferences contribute to such a rapid spread and one should reconsider this model of scientific exchange from time to time and scrutinize potential alternatives. Models for sustainable international conferences are under testing and combine venues in close proximity to institutions with a substantial expertise on the focus area of the conference with virtual participation and contribution by internet for participants on more distant places. Although personal meetings are essential for optimal information exchange, a reduction in travel would not only reduce the risk of dissemination of disease but, as a side effect, could result in budgetary savings, reduce travel‐related emissions (in the wake of Greta), and eliminate jetlag. Now, what can Cytometry do for help in pandemics? Cytometry has already supported several achievements as a quick and non‐representative literature search shows. Image cytometry methods 3 and bead‐based flow cytometry methods 4 are at hand to enable for screening and detecting antibody virus interactions and detect viral antigens. Airway memory T‐cells and viral E protein mutations have been identified in CoV infections a potential targets for vaccine strategies 5, 6. Immune responses seem to be indicative of disease severity 6, 7 but more studies are needed to have a practical assay for decision making at hand. In fact, easy to use and rapid assays derived from Cytomics or multi‐OMICS approaches are needed to rapidly distinguish severe from mild cases and identify future critically ill individuals before symptom onset. Such a test would clearly take the pressure off of the clinicians because only those with high probability to becoming critically ill would receive intensive care early. Hopefully we will see more related studies in this journal in the near future.",2020,"Tárnok, Attila",Cytometry Part A,2949717189,#5479,
,CZI,Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics,10.1002/ddr.21656,,32129518,,"At the time of writing this commentary (February 2020), the coronavirus COVID-19 epidemic has already resulted in more fatalities compared with the SARS and MERS coronavirus epidemics combined. Therapeutics that may assist to contain its rapid spread and reduce its high mortality rates are urgently needed. Developing vaccines against the SARS-CoV-2 virus may take many months. Moreover, vaccines based on viral-encoded peptides may not be effective against future coronavirus epidemics, as virus mutations could make them futile. Indeed, new Influenza virus strains emerge every year, requiring new immunizations. A tentative suggestion based on existing therapeutics, which would likely be resistant to new coronavirus mutations, is to use available angiotensin receptor 1 (AT1R) blockers, such as losartan, as therapeutics for reducing the aggressiveness and mortality from SARS-CoV-2 virus infections. This idea is based on observations that the angiotensin-converting enzyme 2 (ACE2) very likely serves as the binding site for SARS-CoV-2, the strain implicated in the current COVID-19 epidemic, similarly to strain SARS-CoV implicated in the 2002-2003 SARS epidemic. This commentary elaborates on the idea of considering AT1R blockers as tentative treatment for SARS-CoV-2 infections, and proposes a research direction based on datamining of clinical patient records for assessing its feasibility.",2020,"Gurwitz, David",Drug Dev Res,2002765492,#4134,
,CZI,COVID-19: Lessons from SARS and MERS,10.1002/eji.202070035,,32104909,,"Within weeks of the first cases, a series of papers were released detailing the epidemiology of the disease (now termed COVID‐19) [1-3]. By early January 2020 the virus was identified and the sequence determined. The virus (termed SARS‐CoV‐2) shares 88% sequence identity to two coronaviruses found in bats, bat‐SLCoVZC45 and bat‐SL‐CoVZXC21, 79% identity with the Severe Acute Respiratory Syndrome (SARS) coronavirus and 50% identity with Middle Eastern Respiratory Syndrome (MERS) coronavirus [4]. From the first cohort of patients, 8 complete genomes were 99.9% identical in sequence. Given that the typical RNA coronavirus evolves at a rate of 104 nucleotide substitutions per year, this suggests a recent single source emergence in early December or late November 2019 [4]. SARS‐CoV‐2 is thought to be transmitted via contaminated hands, surfaces and aerosolised droplets; extensive human‐to‐human transmission is evident, with clusters of infected families and medical staff [5]. The number of confirmed cases has increased rapidly, at a rate that far outstripped the rate of rise of cases of SARS in 2002/3, raising serious global health concerns. By the 21st January, COVID‐19 cases were widespread across mainland China, soon spreading beyond the Chinese borders.",2020,"Park, Mirae; Thwaites, Ryan S.; Openshaw, Peter J. M.",European journal of immunology,2950551830,#3882,
,CZI,The indispensable role of emergency medicine in national preparedness for high consequence infectious diseases (HCIDs),10.1002/emp2.12041,,,,,2020,"Sánchez, Sarimer M.; Shenoy, Erica S.; Biddinger, Paul D.",Journal of the American College of Emergency Physicians Open,2317345803,#2556,
,CZI,Novel coronavirus pneumonia combined with viral conjunctivitis: three cases report,10.1002/hep.20111,,,,"Since January 2020, as ophthalmologists working at the center of the novel coronavirus pneumonia (NCP) outbreak in Wuhan, China, we found 3 cases in 30 NCP patients with binocular conjunctivitis. Of them, one case visited for conjunctivitis as a first symptom and then diagnosed as NCP, and two cases visited for binocular conjunctivitis during the NCP onset. In 3 patients, conjunctivitis was manifested as signs of viral conjunctivitis from mild to moderate. Their symptoms of two patients disappeared after treatment with antiviral eyedrops for 7 to 10 days and another patient died of NCP. Interestingly,although we detected positive viral nucleic acid in the conjunctiva sacs of 2 of other 27 NCP patients by using swabs and RT-PCR technology, no conjunctivitis occurred in these two patients.",2020,"YE, Ya; SONG, Yanping; YAN, Ming; HU, Cheng; CHEN, Xiao; YU, Juan; REN, Xingfeng",Chinese Journal of Experimental Ophthalmology,2090258227,#2082,
,CZI,Recent advances in the detection of respiratory virus infection in humans,10.1002/jmv.25674,,31944312,,"Respiratory tract viral infection caused by viruses or bacteria is one of the most common diseases in human worldwide, while those caused by emerging viruses, such as the novel coronavirus, 2019-nCoV that caused the pneumonia outbreak in Wuhan, China most recently, have posed great threats to global public health. Identification of the causative viral pathogens of respiratory tract viral infections is important to select an appropriate treatment, save people's lives, stop the epidemics, and avoid unnecessary use of antibiotics. Conventional diagnostic tests, such as the assays for rapid detection of antiviral antibodies or viral antigens, are widely used in many clinical laboratories. With the development of modern technologies, new diagnostic strategies, including multiplex nucleic acid amplification and microarray-based assays, are emerging. This review summarizes currently available and novel emerging diagnostic methods for the detection of common respiratory viruses, such as influenza virus, human respiratory syncytial virus (RSV), coronavirus, human adenovirus (hAdV), and human rhinovirus (hRV). Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. It is anticipated that such data will assist researchers and clinicians to develop appropriate diagnostic strategies for timely and effective detection of respiratory virus infections. This article is protected by copyright. All rights reserved.",2020,"Zhang, N.; Wang, L.; Deng, X.; Liang, R.; Su, M.; He, C.; Hu, L.; Su, Y.; Ren, J.; Yu, F.; Du, L.; Jiang, S.",Journal of medical virology,2999535351,#2,
,CZI,"Emerging coronaviruses: Genome structure, replication, and pathogenesis",10.1002/jmv.25681,,,,"The recent emergence of a novel coronavirus (2019-nCoV), which is causing an outbreak of unusual viral pneumonia in patients in Wuhan, a central city in China, is another warning of the risk of CoVs posed to public health. In this minireview, we provide a brief introduction of the general features of CoVs and describe diseases caused by different CoVs in humans and animals. This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats.",2020,"Chen, Y.; Liu, Q.; Guo, D.",Journal of Medical Virology,3001456238,#989,
,CZI,Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human,10.1002/jmv.25682,,31967321,,"The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019-nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many patients were potentially exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To determine the possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on existing sequences of the newly identified coronavirus 2019-nCoV. Results obtained from our analyses suggest that the 2019-nCoV appears to be a recombinant virus between the bat coronavirus and an origin-unknown coronavirus. The recombination occurred within the viral spike glycoprotein, which recognizes cell surface receptor. Additionally, our findings suggest that snake is the most probable wildlife animal reservoir for the 2019-nCoV based on its RSCU bias resembling snake compared to other animals. Taken together, our results suggest that homologous recombination within the spike glycoprotein may contribute to cross-species transmission from snake to humans. This article is protected by copyright. All rights reserved.",2020,"Ji, W.; Wang, W.; Zhao, X.; Zai, J.; Li, X.",Journal of medical virology,3000771439,#17,
,CZI,Global Health Concern Stirred by Emerging Viral Infections,10.1002/jmv.25683,,,,"Emerging viral infections continue to pose a major threat to global public health. In 1997, a highly pathogenic avian influenza A (H5N1) virus was found to directly spread from poultry to humans unlike previously reported transmission routs of human-to-human and livestock-to-human, stirring a grave concern for a possible influenza pandemic. This article is protected by copyright. All rights reserved.",2020,"Luo, G. G.; Gao, S. J.",Journal of medical virology,3000796089,#124,
,CZI,The 2019‐new coronavirus epidemic: Evidence for virus evolution,10.1002/jmv.25688,,,,"There is a worldwide concern about the new coronavirus 2019‐nCoV as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequences of 2019‐nCoV, 12 whole genome sequences of 2019‐nCoV, and 12 highly similar whole genome sequences available in gene bank (five from the severe acute respiratory syndrome, two from Middle East respiratory syndrome, and five from bat SARS‐like coronavirus). Fast unconstrained Bayesian approximation analysis shows that the nucleocapsid and the spike glycoprotein have some sites under positive pressure, whereas homology modeling revealed some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019‐nCoV significantly clustered with bat SARS‐like coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in Spike Glycoprotein and nucleocapsid protein. From these results, the new 2019‐nCoV is distinct from SARS virus, probably trasmitted from bats after mutation conferring ability to infect humans.",2020,"Benvenuto, Domenico; Giovanetti, Marta; Ciccozzi, Alessandra; Spoto, Silvia; Angeletti, Silvia; Ciccozzi, Massimo",Journal of Medical Virology,,#2364,
,CZI,"Updated understanding of the outbreak of 2019 novel coronavirus (2019‐nCoV) in Wuhan, China",10.1002/jmv.25689,,,,"To help health workers and the public recognize and deal with the 2019 novel coronavirus (2019‐nCoV) quickly, effectively, and calmly with an updated understanding. A comprehensive search from Chinese and worldwide official websites and announcements was performed between 1 December 2019 and 9:30 am 26 January 2020 (Beijing time). A latest summary of 2019‐nCoV and the current outbreak was drawn. Up to 24 pm, 25 January 2020, a total of 1975 cases of 2019‐nCoV infection were confirmed in mainland China with a total of 56 deaths having occurred. The latest mortality was approximately 2.84% with a total of 2684 cases still suspected. The China National Health Commission reported the details of the first 17 deaths up to 24 pm, 22 January 2020. The deaths included 13 males and 4 females. The median age of the people who died was 75 (range 48‐89) years. Fever (64.7%) and cough (52.9%) were the most common first symptoms among those who died. The median number of days from the occurence of the first symptom to death was 14.0 (range 6‐41) days, and it tended to be shorter among people aged 70 years or more (11.5 [range 6‐19] days) than those aged less than 70 years (20 [range 10‐41] days; P = .033). The 2019‐nCoV infection is spreading and its incidence is increasing nationwide. The first deaths occurred mostly in elderly people, among whom the disease might progress faster. The public should still be cautious in dealing with the virus and pay more attention to protecting the elderly people from the virus.
The 2019‐nCoV infection is spreading and its incidence is increasing nationwide. The first occurred deaths were majorly elderly people who might have faster disease progression. Although the current mortality is lower than that of the SARS‐CoV and the MERS‐CoV, it seems that the 2019‐nCoV is very contagious. The public should still be cautious in dealing with the virus and pay more attention to protecting the elderly people from the virus.",2020,"Wang, Weier; Tang, Jianming; Wei, Fangqiang",Journal of Medical Virology,3003790823,#1264,
,CZI,Potential of large 'first generation' human-to-human transmission of 2019-nCoV,10.1002/jmv.25693,,31997390,,"To investigate the genetic diversity, time origin, and evolutionary history of the 2019-nCoV outbreak in China and Thailand, a total of 12 genome sequences of the virus with known sampling date (24 December 2019 and 13 January 2020) and geographic location (primarily Wuhan city, Hubei Province, China, but also Bangkok, Thailand) were analyzed. Phylogenetic and likelihood-mapping analyses of these genome sequences were performed. Based on our results, the star-like signal and topology of 2019-nCoV may be indicative of potentially large 'first generation' human-to-human virus transmission. We estimated that 2019-nCoV likely originated in Wuhan on 9 November 2019 (95% credible interval: 25 September 2019 and 19 December 2019), and that Wuhan is the major hub for the spread of the 2019-nCoV outbreak in China and elsewhere. Our results could be useful for designing effective prevention strategies for 2019-nCoV in China and beyond. This article is protected by copyright. All rights reserved.",2020,"Li, X.; Zai, J.; Wang, X.; Li, Y.",Journal of medical virology,3003224476,#73,
,CZI,Updates on Wuhan 2019 Novel Coronavirus Epidemic,10.1002/jmv.25695,,,,"Abstract What emerged in December 2019 as a cluster of respiratory ailments with inexplicable etiological findings in Wuhan has now claimed roughly 259 lives, sickened nearly 12 thousand more, and spread to at least 26 more nations including Hong Kong, Taiwan and Macao. This article is protected by copyright. All rights reserved.",2020,"Kofi Ayittey, Foster; Dzuvor, Christian; Kormla Ayittey, Matthew; Bennita Chiwero, Nyasha; Habib, Ahmed",Journal of Medical Virology,3005053690,#225,
,CZI,Immunoinformatics-aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019-nCoV,10.1002/jmv.25698,,,,"Abstract The 2019 novel coronavirus (2019-nCoV) outbreak has caused a large number of deaths with thousands of confirmed cases worldwide, especially in East Asia. This study took an immunoinformatics approach to identify significant cytotoxic T lymphocyte (CTL) and B cell epitopes in the 2019-nCoV surface glycoprotein. Also, interactions between identified CTL epitopes and their corresponding MHC class I supertype representatives prevalent in China were studied by molecular dynamics simulations. We identified five CTL epitopes, three sequential B cell epitopes and five discontinuous B cell epitopes in the viral surface glycoprotein. Also, during simulations, the CTL epitopes were observed to be binding MHC class I peptide-binding grooves via multiple contacts, with continuous hydrogen bonds and salt bridge anchors, indicating their potential in generating immune responses. Some of these identified epitopes can be potential candidates for development of 2019-nCoV vaccines. This article is protected by copyright. All rights reserved.",2020,"Baruah, Vargab; Bose, Sujoy",Journal of Medical Virology,3005011674,#344,
,CZI,The first two cases of 2019-nCoV in Italy: where they come from?,10.1002/jmv.25699,,,,"ABSTRACT A novel Coronavirus, 2019-nCoV, has been identified as the causal pathogen of an ongoing epidemic, with the first cases reported in Wuhan, China, last December 2019, and has since spread to other countries worldwide, included Europe and very recently Italy. In this short report, phylogenetic reconstruction was used to better understand the transmission dynamic of the virus from its first introduction in China focusing on the more recent evidence of infection in a couple of Chinese tourists arrived in Italy on 23rd January 2020 and labeled as Coronavirus Italian cases. A Maximum Clade Credibility tree has been built using a dataset of 54 genome sequences of 2019-nCoV plus 2 closely related bat strains (SARS-like CoV) available in GeneBank. Bayesian time-scaled phylogenetic analysis was implemented in BEAST 1.10.4. The Bayesian phylogenetic reconstruction showed that the 2019-2020 nCoV firstly introduced in Wuhan on the 25th November 2019, started epidemic transmission reaching many countries worldwide, including Europe and Italy where the two strains isolated dated back 19th January 2020, the same that the Chinese tourists arrived in Italy. Strains isolated outside China were intermixed with strains isolated in China as evidence of likely imported cases in Rome, Italy and Europe, as well. In conclusion, this report suggests that further spread of 2019-nCoV epidemic was supported by human mobility and that quarantine of suspected or diagnosed cases is useful to prevent further transmission. Viral genome phylogenetic analysis represents a useful tool for evaluation of transmission dynamics and preventive action. This article is protected by copyright. All rights reserved.",2020,"Giovanetti, Marta; Benvenuto, Domenico; Angeletti, Silvia; Ciccozzi, Massimo",Journal of Medical Virology,3004815273,#321,
,CZI,Genomic variance of the 2019-nCoV coronavirus,10.1002/jmv.25700,,,,"Abstract There is rising global concern for the recently emerged novel Coronavirus (2019-nCov). Full genomic sequences have been released by the worldwide scientific community in the last few weeks in order to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and SARS. We confirm high sequence similarity (>99%) between all sequenced 2019-nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019-nCoV. Despite the low heterogeneity of the 2019-nCoV genomes, we could identify at least two hyper-variable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8-encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti-coronavirus approaches. This article is protected by copyright. All rights reserved.",2020,"Ceraolo, Carmine; Giorgi, Federico M.",Journal of Medical Virology,3004499272,#421,
,CZI,Transmission dynamics and evolutionary history of 2019-nCoV,10.1002/jmv.25701,,,,"Abstract To investigate the time origin, genetic diversity, and transmission dynamics of the recent 2019-nCoV outbreak in China and beyond, a total of 32 genomes of virus strains sampled from China, Thailand, and USA with sampling dates between 24 December 2019 and 23 January 2020 were analyzed. Phylogenetic, transmission network, and likelihood-mapping analyses of the genome sequences were performed. Based on likelihood-mapping analysis, the increasing tree-like signals (from 0 to 8.2%, 18.2%, and 25.4%) over time may be indicative of increasing genetic diversity of 2019-nCoV in human hosts. We identified three phylogenetic clusters using the Bayesian inference framework and three transmission clusters using transmission network analysis, with only one cluster identified by both methods using the above genome sequences of 2019-nCoV strains. The estimated mean evolutionary rate for 2019-nCoV ranged from 1.7926 ? 10-3 to 1.8266 ? 10-3 substitutions per site per year. Based on our study, undertaking epidemiological investigations and genomic data surveillance could positively impact public health in terms of guiding prevention efforts to reduce 2019-nCOV transmission in real time. This article is protected by copyright. All rights reserved.",2020,"Li, Xingguang; Wang, Wei; Zhao, Xiaofang; Zai, Junjie; Zhao, Qiang; Li, Yi; Chaillon, Antoine",Journal of Medical Virology,3004826757,#396,
,CZI,Evolving status of the 2019 novel coronavirus Infection: proposal of conventional serologic assays for disease diagnosis and infection monitoring [Commentary/Review],10.1002/jmv.25702,,,,"Abstract The novel coronavirus (nCoV-2019) outbreak in Wuhan, China has spread rapidly nationwide, with some cases occurring in other parts of the world. Although most patients present with mild febrile illness with patchy pulmonary inflammation, a significant portion develop severe acute respiratory distress syndrome (ARDS), with a current case fatality of 2.3-3%. Diagnosis is based on clinical history and laboratory and chest radiographic findings, but confirmation currently relies on nucleic acid-based assays. The latter are playing an important role in facilitating patient isolation, treatment and assessment of infectious activities. However, due to their limited capacity to handle an epidemic of the current scale and insufficient supply of assay kits, only a portion of suspected cases can be tested, leading to incompleteness and inaccuracy in updating new cases, as well as delayed diagnosis. Furthermore, there has not been enough time to assess specificity and sensitivity. Conventional serological assays, such as enzyme-linked immunoassay (ELISA) for specific IgM and IgG antibodies, should offer a high-throughput alternative, which allows for uniform tests for all suspected patients, and can facilitate more complete identification of infected cases and avoidance of unnecessary cross infection among unselected patients. This article is protected by copyright. All rights reserved.",2020,"Xiao, Shu-Yuan; Wu, Yingjie; Liu, Huan",Journal of Medical Virology,3005036059,#529,
,CZI,The progress of 2019 Novel Coronavirus (2019-nCoV) event in China,10.1002/jmv.25705,,32048741,,"It has been more than one month since the first 2019-nCov infected person was diagnosed. However, the number of cumulative cases is keeping upward, including the severe cases and death cases. It has been proved that droplets transmission is the major route for 2019-nCov infection, and interpersonal contact could also cause the disease. Due to the fast-growing of Wuhan pneumonia and relative low cure rate, Chinese government is facing great challenges, and has taken emergency measures on disease prevention and clinical treatment, including population mobility control, building five or more hospitals for Wuhan pneumonia treatment, such as ""Huo Shen Shan"" hospital as well as developing a specific vaccine. In the meanwhile, the government shared the updated Genome Sequence of 2019-nCoV to the public, and scientists from China and oversea are working tightly and efficiently on public health emergency. This article is protected by copyright. All rights reserved.",2020,"Guan, Wang; Xian, Jin",J Med Virol,3005586597,#774,
,CZI,Economic Impacts of Wuhan 2019-nCoV on China and the World,10.1002/jmv.25706,,32048740,,"Uncertainties over the Wuhan 2019 Novel Coronavirus (2019-nCoV), which has killed 1,017 people and sickened more than 43,100 as of Feb 11,(1) has interrupted global trade and supply chains, depressed asset prices, and forced multinational businesses to make hard decisions with limited information. This article is protected by copyright. All rights reserved.",2020,"Ayittey, Foster Kofi; Ayittey, Matthew Kormla; Chiwero, Nyasha Bennita; Kamasah, Japhet Senyo; Dzuvor, Christian",J Med Virol,3005741104,#799,
,CZI,Potential Interventions for Novel Coronavirus in China: A Systemic Review,10.1002/jmv.25707,,32052466,,"An outbreak of a novel coronavirus (COVID-19 or 2019-CoV) infection has posed significant threats to international health and the economy. In the absence of treatment for this virus, there is an urgent need to find alternative methods to control the spread of disease. Here, we have conducted an online search for all treatment options related to coronavirus infections as well as some RNA virus infection and we have found that general treatments, coronavirus-specific treatments, and antiviral treatments should be useful in fighting COVID-19. We suggest that the nutritional status of each infected patient should be evaluated before the administration of general treatments and the current children's RNA virus vaccines including influenza vaccine should be immunized for uninfected people and health care workers. In addition, convalescent plasma should be given to COVID-19 patients if it is available. In conclusion, we suggest that all the potential interventions be implemented to control the emerging COVID-19 if the infection is uncontrollable. This article is protected by copyright. All rights reserved.",2020,"Zhang, Lei; Liu, Yunhui",J Med Virol,3006252254,#854,
,CZI,Does SARS-CoV-2 has a longer incubation period than SARS and MERS?,10.1002/jmv.25708,,,,"Abstract The outbreak of a novel coronavirus (SARS-CoV-2) since Dec 2019 in Wuhan, the major transportation hub in central China, became an emergency of major international concern. While several etiological studies have begun to reveal the specific biological features of this virus, the epidemic characteristics need to be elucidated. Notably, a long incubation time was reported to be associated with SARS-CoV-2 infection, leading to adjustments in screening and control policies. To avoid the risk of virus spread, all potentially exposed subjects are required to be isolated for 14 days, which is the longest predicted incubation time. However, based on our analysis of a larger dataset available so far, we find there is no observable difference between the incubation time for SARS-CoV-2, SARS and MERS, highlighting the need for larger and well annotated datasets. This article is protected by copyright. All rights reserved.",2020,"Jiang, Xuan; Rayner, Simon; Luo, Min-Hua",Journal of Medical Virology,3005802419,#857,
,CZI,"Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV",10.1002/jmv.25709,,,,"Abstract First reported from Wuhan, PR China, on 31 December 2019, the ongoing outbreak of a novel coronavirus (2019-nCoV) causes great global concerns. Based on the advice of the International Health Regulations Emergency Committee and the fact that to date 24 other countries also reported cases, the WHO Director-General declared that the outbreak of 2019-nCoV constitutes a Public Health Emergency of International Concern on 30 January 2020. Together with the other two highly pathogenic coronaviruses, the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), 2019-nCov and other yet to be identified coronaviruses pose a global threat to public health. In this mini-review, we provide a brief introduction on the pathology and pathogenesis of SARS-CoV and MERS-CoV, and extrapolate this knowledge to the newly identified 2019-nCoV. This article is protected by copyright. All rights reserved.",2020,"Liu, Jia; Zheng, Xin; Tong, Qiaoxia; Li, Wei; Wang, Baoju; Sutter, Kathrin; Trilling, Mirko; Lu, Mengji; Dittmer, Ulf; Yang, Dongliang",Journal of Medical Virology,3005949806,#856,
,CZI,The course of clinical diagnosis and treatment of a case infected with coronavirus disease 2019,10.1002/jmv.25711,,,,"Abstract A pneumonia outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first identified in Wuhan, present a major threat to public health since December 2019. There are more than 50,000 confirmed cases and 1300 dead cases worldwide for the past month or more, because of the occurrence of a highly contagious performance. Patients had clinical manifestations of fever, cough, shortness of breath, diarrhea, vomiting and so on. We herein report a case of SARS-CoV-2, describe the epidemic history, clinical diagnosis and the changes of clinical parameters during the combination therapy. This article is protected by copyright. All rights reserved.",,"Han, Wenzheng; Quan, Bin; Guo, Wei; Zhang, Jun; Lu, Yong; Feng, Gang; Wu, Qiwen; Fang, Fang; Cheng, Long; Jiao, Nanlin; Li, Xiaoning; Chen, Qing",Journal of Medical Virology,2416899403,#1304,
,CZI,Antibodies to Coronaviruses Are Higher in Older Compared with Younger Adults and Binding Antibodies Are More Sensitive than Neutralizing Antibodies in Identifying Coronavirus-Associated Illnesses,10.1002/jmv.25715,,,,"ABSTRACT Problem Human coronaviruses (HCoV) are common causes of respiratory illnesses (RI) despite pre-existing humoral immunity. Methods Sera were obtained near onset of RI and 3 to 4 weeks later as part of a prospective study of 200 subjects evaluated for RI from 2009 to 2013. Antibodies against common HCoV strains were measured by enzyme-linked immunosorbent assay (ELISA) and neutralization assay comparing older adults with cardiopulmonary diseases (99 subjects) to younger, healthy adults (101 subjects). Virus shedding was detected in respiratory secretions by polymerase chain reaction. Results Of 43 HCoV-associated illnesses, 15 (35%) occurred in 14 older adults (aged ≥ 60 years) and 28 (65%) in 28 younger adults (aged 21 to 40 years). Binding and neutralizing antibodies were higher in older adults. Only 16 (35.7%) of RI with increases in binding antibodies also had increases in neutralizing antibodies to HCoV. Increases in binding antibodies with RI were more frequent than increased neutralizing antibodies and virus shedding, and more frequent in younger compared to older adults. Conclusions Functional neutralizing antibodies were not stimulated as often as binding antibodies, explaining in part a susceptibility to reinfection with HCoV. Monitoring binding antibodies may be more sensitive for serologic detection of HCoV infections. This article is protected by copyright. All rights reserved.",,"Gorse, Geoffrey J.; Donovan, Mary M.; Patel, Gira B.",Journal of Medical Virology,2089727343,#1307,
,CZI,COVID-2019: the role of the nsp2 and nsp3 in its pathogenesis,10.1002/jmv.25719,,32083328,,"Last December 2019, a new virus, named COVID-2019 causing many cases of severe pneumonia was reported in Wuhan, China. The virus knowledge is limited and especially about COVID-2019 pathogenesis. The Open Reading Frame 1ab (ORF1ab) of COVID-2019 has been analyzed to evidence the presence of mutation caused by selective pressure on the virus. For selective pressure analysis fast-unconstrained Bayesian approximation (FUBAR) was used. Homology modelling has been performed by SwissModel and HHPred servers. The presence of transmembrane helical segments in Coronavirus ORF1ab nsp2 and nsp3, was tested by TMHMM, MEMSAT and MEMPACK tools. Three-dimensional structures have been analyzed and displayed using PyMOL. FUBAR analysis revealed the presence of potential sites under positive selective pressure (p-value < 0.05). Position 723 in the COVID-2019 has a serine instead a glycine residue, while at aminoacidic position 1010 a proline instead an isoleucine. Significant (p < 0.05) pervasive negative selection in 2416 sites (55%) was found. The positive selective pressure could account for some clinical features of this virus compared to SARS and Bat SARS-like CoV. The stabilizing mutation falling in the endosome-associated-protein-like domain of the nsp2 protein could account for COVID-2019 high ability of contagious, while the destabilizing mutation in nsp3 proteins could suggest a potential mechanism differentiating COVID-2019 from SARS. These data could be helpful for further investigation aimed to identify potential therapeutic targets or vaccine strategy, especially in the actual moment when the epidemic is ongoing and the scientific community is trying to enrich knowledge about this new viral pathogen. This article is protected by copyright. All rights reserved.",2020,"Angeletti, Silvia; Benvenuto, Domenico; Bianchi, Martina; Giovanetti, Marta; Pascarella, Stefano; Ciccozzi, Massimo",J Med Virol,3003752833,#1704,
,CZI,Facing the COVID-19 outbreak: What should we know and what could we do?,10.1002/jmv.25720,,32091134,,"A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, Hubei Province in China in December 2019 and caused a serious type of pneumonia called coronavirus disease 2019 or COVID-19. This epidemic quickly spread across China and extended to more than 20 other countries. This commentary discusses the reasons for the fast spread of SARS-CoV-2 in three aspects: the infectious sources, including the biological nature of the virus; the susceptible population; and the transmission routes. The current situations and suggestions regarding the control of the disease are summarized. This article is protected by copyright. All rights reserved.",2020,"Yang, Yi; Shang, Weilong; Rao, Xiancai",J Med Virol,3006304371,#1731,
,CZI,Combination of RT-qPCR Testing and Clinical Features For Diagnosis of COVID-19 facilitates management of SARS-CoV-2 Outbreak,10.1002/jmv.25721,,32096564,,"In December 2019, a cluster of acute respiratory illness occurred in Wuhan, Hubei Province, China. This disease is now officially known as 2019 novel coronavirus disease (COVID-19) from WHO, novel coronavirus pneumonia This article is protected by copyright. All rights reserved.",2020,"Wang, Yishan; Kang, Hanyujie; Liu, Xuefeng; Tong, Zhaohui",J Med Virol,2060528165,#1919,
,CZI,Understanding of COVID-19 based on current evidence,10.1002/jmv.25722,,32096567,,"Since December 2019, a series of unexplained pneumonia cases has been reported in Wuhan, China. On January 12, 2020, the World Health Organization (WHO) temporarily named this new virus as the 2019 novel coronavirus (2019-nCoV). On February 11, 2020, the WHO officially named the disease caused by the 2019-nCoV as Corona Virus Disease (COVID-19). The COVID-19 epidemic is spreading all over the world, especially in China. Based on the published evidence, we systematically discuss the characteristics of COVID-19 in the hope of providing a reference for future studies and help for the prevention and control of the COVID-19 epidemic. This article is protected by copyright. All rights reserved.",2020,"Sun, Pengfei; Lu, Xiaosheng; Xu, Chao; Sun, Wenjuan; Pan, Bo",J Med Virol,2513700352,#1931,
,CZI,Early Phylogenetic Estimate of the Effective Reproduction Number Of Sars-CoV-2,10.1002/jmv.25723,,32096566,,"To reconstruct the evolutionary dynamics of the 2019 novel coronavirus recently causing an outbreak in Wuhan, China, 52 SARS-CoV-2 genomes available on 04 February 2020 at GISAID were analysed. The two models used to estimate the reproduction number (coalescent-based exponential growth and a birth-death skyline method) indicated an estimated mean evolutionary rate of 7.8 x 10(-4) subs/site/year (range 1.1x10(-4) -15x10(-4) ) and a mean tMRCA of the tree root of 73 days. The estimated R value was 2.6 (range 2.1-5.1), and increased from 0.8 to 2.4 in December 2019. The estimated mean doubling time of the epidemic was between 3.6 and 4.1 days. This study proves the usefulness of phylogeny in supporting the surveillance of emerging new infections even as the epidemic is growing. This article is protected by copyright. All rights reserved.",2020,"Lai, Alessia; Bergna, Annalisa; Acciarri, Carla; Galli, Massimo; Zehender, Gianguglielmo",J Med Virol,2123665197,#1969,
,CZI,Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection,10.1002/jmv.25725,,32100876,,"OBJECTIVE: This study aimed to assess the presence of novel coronavirus in tears and conjunctival secretions of SARS-CoV-2 infected patients. METHODS: A prospective interventional case series study was performed, and 30 confirmed novel coronavirus pneumonia (NCP) patients were selected at the First Affiliated Hospital of Zhejiang University from January 26, 2020 to February 9, 2020. At an interval of 2-3 days, tear and conjunctival secretions were collected twice with disposable sampling swabs for reverse transcription polymerase chain reaction (RT-PCR) assay. RESULTS: 21 common type and 9 severe type NCP patients were enrolled. Two samples of tear and conjunctival secretions were obtained from the only one patient with conjunctivitis yielded positive RT-PCR results. 58 samples from other patents were all negative. CONCLUSION: We speculate that SARS-CoV-2 may be detected in the tears and conjunctival secretions in NCP patients with conjunctivitis. This article is protected by copyright. All rights reserved.",2020,"Xia, Jianhua; Tong, Jianping; Liu, Mengyun; Shen, Ye; Guo, Dongyu",J Med Virol,3006355661,#2115,
,CZI,Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2,10.1002/jmv.25726,,32100877,,"From the beginning of 2002 and 2012, severe respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) crossed the species barriers to infect humans caused thousands of infections and hundreds of deaths, respectively. Currently, a novel coronavirus (SARS-CoV-2) causes the outbreaks of Coronavirus Disease 2019 (COVID-19) was discovered. Until February 18, 2020, there are 72533 confirmed COVID-19 cases (including 10644 severe cases) and 1872 deaths in China. SARS-CoV-2 is surging in the public and caused substantial burdens due to its human-to-human transmission. However, the intermediate host of SARS-CoV-2 is still unclear. Finding the possible intermediate host of SARS-CoV-2 is imperative to prevent further spread of the epidemic. In this study, we used systematic comparison and analysis to predict the interaction between the receptor binding domain (RBD) of coronavirus spike protein and the host receptor, Angiotensin Converting Enzyme 2 (ACE2). The interaction between the key amino acids of S protein RBD and ACE2 indicated that like previous suggested pangolins and snacks, the turtles (C. picta bellii, C. mydas, and P. sinensis) may act as the potential intermediate hosts transmitting SARS-CoV-2 to human. This article is protected by copyright. All rights reserved.",2020,"Liu, Zhixin; Xiao, Xiao; Wei, Xiuli; Li, Jian; Yang, Jing; Tan, Huabing; Zhu, Jianyong; Zhang, Qiwei; Wu, Jianguo; Liu, Long",J Med Virol,2513547424,#2181,
,CZI,Development and Clinical Application of A Rapid IgM-IgG Combined Antibody Test for SARS-CoV-2 Infection Diagnosis,10.1002/jmv.25727,,,,"Abstract The outbreak of the novel coronavirus disease (COVID-19) quickly spread all over China and to more than 20 other countries. Although the virus (SARS-Cov-2) nucleic acid RT-PCR test has become the standard method for diagnosis of SARS-CoV-2 infection, these real-time PCR test kits have many limitations. In addition, high false negative rates were reported. There is an urgent need for an accurate and rapid test method to quickly identify large number of infected patients and asymptomatic carriers to prevent virus transmission and assure timely treatment of patients. We have developed a rapid and simple point-of-care lateral flow immunoassay which can detect IgM and IgG antibodies simultaneously against SARS-CoV-2 virus in human blood within 15 minutes which can detect patients at different infection stages. With this test kit, we carried out clinical studies to validate its clinical efficacy uses. The clinical detection sensitivity and specificity of this test were measured using blood samples collected from 397 PCR confirmed COVID-19 patients and 128 negative patients at 8 different clinical sites. The overall testing sensitivity was 88.66% and specificity was 90.63%. In addition, we evaluated clinical diagnosis results obtained from different types of venous and fingerstick blood samples. The results indicated great detection consistency among samples from fingerstick blood, serum and plasma of venous blood. The IgM-IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test. It can be used for the rapid screening of SARS-CoV-2 carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories. This article is protected by copyright. All rights reserved.",2020,"Li, Zhengtu; Yi, Yongxiang; Luo, Xiaomei; Xiong, Nian; Liu, Yang; Li, Shaoqiang; Sun, Ruilin; Wang, Yanqun; Hu, Bicheng; Chen, Wei; Zhang, Yongchen; Wang, Jing; Huang, Baofu; Lin, Ye; Yang, Jiasheng; Cai, Wensheng; Wang, Xuefeng; Cheng, Jing; Chen, Zhiqiang; Sun, Kangjun; Pan, Weimin; Zhan, Zhifei; Chen, Liyan; Ye, Feng",Journal of Medical Virology,2940585450,#2600,
,CZI,A Systematic Review of Lopinavir Therapy for SARS Coronavirus and MERS Coronavirus–A Possible Reference for Coronavirus Disease-19 Treatment Option,10.1002/jmv.25729,,,,"Abstract In the past few decades, coronaviruses have risen as a global threat to public health. Currently, the outbreak of coronavirus disease-19 (COVID-19) from Wuhan caused a worldwide panic. There are no specific antiviral therapies for COVID-19. However, there are agents that were used during the SARS and MERS epidemics. We could learn from SARS and MERS. Lopinavir (LPV) is an effective agent that inhibits the protease activity of coronavirus. In this review, we discuss the literature on the efficacy of LPV in vitro and in vivo, especially in patients with SARS and MERS, so that we might clarify the potential for the use of LPV in patients with COVID-19. This article is protected by copyright. All rights reserved.",2020,"Yao, Tian-Tian; Qian, Jian-Dan; Zhu, Wen-Yan; Wang, Yan; Wang, Gui-Qiang",Journal of Medical Virology,,#2495,
,CZI,"Evolutionary history, potential intermediate animal host, and cross-species analyses of SARS-CoV-2",10.1002/jmv.25731,,,,"Abstract To investigate the evolutionary history of the recent outbreak of SARS-CoV-2 in China, a total of 70 genomes of virus strains from China and elsewhere with sampling dates between 24 December 2019 and 3 February 2020 were analyzed. To explore the potential intermediate animal host of the SARS-CoV-2 virus, we re-analyzed virome datasets from pangolins and representative SARS-related coronaviruses isolates from bats, with particular attention paid to the spike glycoprotein gene. We performed phylogenetic, split network, transmission network, likelihood-mapping, and comparative analyses of the genomes. Based on Bayesian time-scaled phylogenetic analysis using the tip-dating method, we estimated the time to the most recent common ancestor (TMRCA) and evolutionary rate of SARS-CoV-2, which ranged from 22?24 November 2019 and 1.19?1.31 ? 10-3 substitutions per site per year, respectively. Our results also revealed that the BetaCoV/bat/Yunnan/RaTG13/2013 virus was more similar to the SARS-CoV-2 virus than the coronavirus obtained from the two pangolin samples (SRR10168377 and SRR10168378). We also identified a unique peptide (PRRA) insertion in the human SARS-CoV-2 virus, which may be involved in the proteolytic cleavage of the spike protein by cellular proteases, and thus could impact host range and transmissibility. Interestingly, the coronavirus carried by pangolins did not have the RRAR motif. Therefore, we concluded that the human SARS-CoV-2 virus, which is responsible for the recent outbreak of COVID-19, did not come directly from pangolins. This article is protected by copyright. All rights reserved.",2020,"Li, Xingguang; Zai, Junjie; Zhao, Qiang; Nie, Qing; Li, Yi; Foley, Brian T.; Chaillon, Antoine",Journal of Medical Virology,858457542,#2602,
,CZI,Clinical trial analysis of 2019-nCoV therapy registered in China,10.1002/jmv.25733,,,,"Abstract So far, there is a lack of effective drugs for the new coronavirus pneumonia. With more and more patients diagnosed, China has carried out more than one hundred clinical studies of new coronavirus infection, including antiviral drugs, antimalarial drugs, glucocorticoids, plasma therapy, virus vaccine and other western drugs, while Chinese medicine researches accounted for half of studies. Most of the trials were initiated by investigators and the study period would last for one to eleven months. The primary endpoints included symptom improvement and virus nucleic acid turning negative, but the optimal endpoint has not been determined. Although the final results of studies will take a long time to complete, the interim research data may provide some help for the current urgent demand for drug treatment. Compared with that of during SARS period in 2003, China have the stronger capability to carry out clinical trials of new drugs in emergency period. This article is protected by copyright. All rights reserved.",2020,"Zhang, Qi; Wang, Yakun; Qi, Changsong; Shen, Lin; Li, Jian",Journal of Medical Virology,3005811358,#3022,
,CZI,Clinical characteristics of 50466 hospitalized patients with 2019-nCoV infection,10.1002/jmv.25735,,,,"Abstract Objective We aim to summarize reliable evidences of evidence-based medicine for the treatment and prevention of the 2019 novel coronavirus (2019-nCoV) by analyzing all the published studies on the clinical characteristics of patients with 2019-nCoV. Methods PubMed, Cochrane Library, Embase, and other databases were searched. Several studies on the clinical characteristics of 2019-nCoV infection were collected for Meta-analysis. Results Ten studies were included in Meta-analysis, including a total number of 50466 patients with 2019-nCoV infection. Meta-analysis shows that, among these patients, the incidence of fever was 89.1%, the incidence of cough was 72.2%, and the incidence of muscle soreness or fatigue was 42.5%. The incidence of acute respiratory distress syndrome (ARDS) was 14.8%, the incidence of abnormal chest computer tomography (CT) was 96.6%, the percentage of severe cases in all infected cases was 18.1%, and the case fatality rate of patients with 2019-nCoV infection was 4.3%. Conclusion Fever and cough are the most common symptoms in patients with 2019-nCoV infection, and most of these patients have abnormal chest CT examination. Several people have muscle soreness or fatigue as well as ARDS. Diarrhea, hemoptysis, headache, sore throat, shock, and other symptoms only occur in a small number of patients. The case fatality rate of patients with 2019-nCoV infection is lower than that of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). This article is protected by copyright. All rights reserved.",2020,"Sun, Pengfei; Qie, Shuyan; Liu, Zongjan; Ren, Jizhen; Li, Kun; Xi, Jianing",Journal of Medical Virology,2034423661,#2949,
,CZI,Development of epitope-based peptide vaccine against novel Coronavirus 2019 (SARS-COV-2): Immunoinformatics approach,10.1002/jmv.25736,,,,"ABSTRACT Recently, a novel Coronavirus (SARS-COV-2) emerged which is responsible for the recent outbreak in Wuhan, China. Genetically, it is closely related to the SARS-CoV and MERS-CoV. The situation is getting worse and worse, therefore, there is an urgent need for designing a suitable peptide vaccine component against the SARS-COV-2. Here, we characterized spike glycoprotein to obtain immunogenic epitopes. Next, we chose 13 Major Histocompatibility Complex-(MHC) I and 3 MHC-II epitopes, having antigenic properties. These epitopes are usually linked to specific linkers to build vaccine components and molecularly dock on Toll-Like Receptor (TLR)-5 to get binding affinity. Therefore, in order to provide a fast immunogenic profile of these epitopes we performed immunoinformatics analysis so that rapid development of vaccine might bring this disastrous situation to the end earlier. This article is protected by copyright. All rights reserved.",2020,"Bhattacharya, Manojit; Ranjan Sharma, Ashish; Patra, Prasanta; Ghosh, Pratik; Sharma, Garima; Chandra Patra, Bidhan; Lee, Sang-Soo; Chakraborty, Chiranjib",Journal of Medical Virology,3004614392,#2731,
,CZI,The Wuhan SARS-CoV-2 – What's Next for China,10.1002/jmv.25738,,,,"Abstract When an outbreak of pneumonia of unknown etiology occurred in Wuhan city, Hubei Province, China in December of 2019, the mystery1 was the nature of the causative agent. Because many of the patients had visited a fish and wild animal market, the possibility of a recurrence of severe acute respiratory syndrome (SARS) needed to be investigated2. Finally, could this outbreak of pneumonia be caused by a novel coronavirus that was different from those causing SARS or Middle East respiratory syndrome (MERS)3? This article is protected by copyright. All rights reserved.",2020,"Lu, Hongzhou; Stratton, Charles W.; Tang, Yi-Wei",Journal of Medical Virology,,#2894,
,CZI,Coronavirus disease (COVID-19) and neonate: What neonatologist need to know,10.1002/jmv.25740,,,,"Abstract Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) cause china epidemics with high morbidity and mortality, the infection has been transmitted to other countries. About 3 neonates and more than 230 children cases are reported. The disease condition of mainly children was mild. There is currently no evidence that SARS-CoV-2can be transmitted transplacentally from mother to the newborn. The treatment strategy for children with Coronavirus disease (COVID-19) is based on adult experience. Thus far, no deaths have been reported in the paediatric age group. This review describes the current understanding of COVID-19 infection in newborns and children. This article is protected by copyright. All rights reserved.",2020,"Lu, Qi; Shi, Yuan",Journal of Medical Virology,2604381070,#2896,
,CZI,Fecal specimen diagnosis 2019 Novel Coronavirus-Infected Pneumonia,10.1002/jmv.25742,,32124995,,"The emergence and spread of 2019 Novel Coronavirus-Infected Pneumonia (COVID-19) from Wuhan, China, it has spread globally. We extracted the data on 14 patients with laboratory-confirmed COVID-19 from Jinhua Municipal Central hospital through January 27th, 2020. We found that compared to pharyngeal swab specimens, nucleic acid detection of COVID-19 in fecal specimens was equally accurate. And we found that patients with a positive stool test did not experience gastrointestinal symptoms and had nothing to do with the severity of the lung infection. These results may help to understand the clinical diagnosis and the changes of clinical parameters of COVID-19. This article is protected by copyright. All rights reserved.",2020,"Zhang, JingCheng; Wang, SaiBin; Xue, YaDong",J Med Virol,3004824173,#3250,
,CZI,Analyzing the Epidemiological Outbreak of COVID-19: A Visual Exploratory Data Analysis (EDA) Approach,10.1002/jmv.25743,,32124990,,"There is an obvious concern globally regarding the fact about the emerging coronavirus 2019-nCoV as a worldwide public health threat. As the outbreak of COVID-19 causes by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) progresses within China and beyond, rapidly available epidemiological data are needed to guide strategies for situational awareness and intervention. The recent outbreak of pneumonia in Wuhan, China caused by the SARS-CoV-2 emphasizes the importance of analyzing the epidemiological data of this novel virus and predicting their risks of infecting people all around the globe. In this article, we present an effort to compile and analyze epidemiological outbreak information on COVID-19 based on the several open datasets on Novel Corona Virus 2019 provided by the Johns Hopkins University, World Health Organization (WHO), Chinese Center for Disease Control and Prevention (CDC), National Health Commission (NHC), and DXY. An Exploratory Data Analysis (EDA) with visualizations has been made in order to understand the number of different cases reported (confirmed, death, recovered) in different provinces of China and outside of China. Overall, at the outset of an outbreak like this, it is highly important to readily provide information in order to begin the evaluation necessary to understand the risks and begin containment activities. This article is protected by copyright. All rights reserved.",2020,"Dey, Samrat Kumar; Rahman, Md Mahbubur; Siddiqi, Umme Raihan; Howlader, Arpita",J Med Virol,2167830100,#3419,
,CZI,Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures,10.1002/jmv.25748,,,,"Abstract By Feb 27th, 2020, the outbreak of COVID-19 caused 82623 confirmed cases and 2858 deaths globally, more than Severe Acute Respiratory Syndrome (SARS) (8273 cases, 775 deaths) and Middle East Respiratory Syndrome (MERS) (1139 cases, 431 deaths) caused in 2003 and 2013 respectively. COVID-19 has spread to 46 countries internationally. Total fatality rate of COVID-19 is estimated at 3.46% by far based on published data from Chinese Center for Disease Control and Prevention (China CDC). Average incubation period of COVID-19 is around 6.4 days, ranges from 0-24 days. The basic reproductive number (R0) of COVID-19 ranges from 2-3.5 at the early phase regardless of different prediction models, which is higher than SARS and MERS. A study from China CDC showed majority of patients (80.9%) were considered asymptomatic or mild pneumonia but released large amounts of viruses at the early phase of infection, which posed enormous challenges for containing the spread of COVID-19. Nosocomial transmission was another severe problem. 3019 health workers were infected by Feb 12, 2020, which accounted for 3.83% of total number of infections, and extremely burdened the health system, especially in Wuhan. Limited epidemiological and clinical data suggest that the disease spectrum of COVID-19 may differ from SARS or MERS. We summarize latest literatures on genetic, epidemiological, and clinical features of COVID-19 in comparison to SARS and MERS and emphasize special measures on diagnosis and potential interventions. This review will improve our understanding of the unique features of COVID-19 and enhance our control measures in the future. This article is protected by copyright. All rights reserved.",2020,"Wang, Yixuan; Wang, Yuyi; Chen, Yan; Qin, Qingsong",Journal of Medical Virology,3005929298,#4416,
,CZI,The transmission and diagnosis of 2019 novel coronavirus infection disease (COVID-19): A Chinese perspective,10.1002/jmv.25749,,32141619,,"2019 novel coronavirus (SARS-CoV-2), which originated in Wuhan, China, has attracted the world's attention over the last month. The Chinese government has taken emergency measures to control the outbreak and has undertaken initial steps in the diagnosis and treatment of 2019 novel coronavirus infection disease (COVID-19). However, SARS-CoV-2 possesses powerful pathogenicity as well as transmissibility and still holds many mysteries that are yet to be solved, such as whether the virus can be transmitted by asymptomatic patients or by mothers to their infants. Our research presents selected available cases of COVID-19 in China to better understand the transmission and diagnosis regarding this infectious disease. This article is protected by copyright. All rights reserved.",2020,"Han, Y.; Yang, H.",Journal of medical virology,3005036059,#4709,
,CZI,Transmission dynamics of the COVID-19 outbreak and effectiveness of government interventions: A data-driven analysis,10.1002/jmv.25750,,32141624,,"Using the parameterized SEIR model, we simulated the spread dynamics of COVID-19 outbreak and impact of different control measures, conducted the sensitivity analysis to identify the key factor, plotted the trend curve of effective reproductive number(R) and performed data fitting after the simulation. By simulation and data fitting, the model showed the peak existing confirmed cases of 59769 arriving on 15 February 2020, with coefficient of determination close to 1 and the fitting bias 3.02%, suggesting high precision of the data fitting results. More rigorous government control policies were associated with slower increase of the infected population. Isolation and protective procedures would be less effective as more cases accrue, so the optimization of treatment plan and the development of specific drugs would be of more importance. There was an upward trend of R in the beginning, followed by a downward trend, a temporary rebound and another continuous decline. The feature of high infectiousness for sars-cov-2 led to the upward trend, and government measures contributed to the temporary rebound and declines. The declines of R could be exploited as strong evidence for the effectiveness of the interventions. Evidence from the four-phase stringent measures showed that it was significant to ensure early detection, early isolation, early treatment, adequate medical supplies, patients' being admitted to designated hospitals and comprehensive therapeutic strategy. Collaborative efforts are required to combat the novel coronavirus, focusing on both persistent strict domestic interventions and vigilance against exogenous imported cases. This article is protected by copyright. All rights reserved.",2020,"Fang, Y.; Nie, Y.; Penny, M.",Journal of medical virology,3006211350,#4665,
,CZI,Strategies suggested for emergency diagnosis and treatment of traumatic orthopedicsin the epidemic periodof Corona Virus Disease 2019,10.1002/jnr.24132,,,,"Objective To suggest strategies for emergency diagnosis and treatment of trauma orthopedics in the epidemic period of Corona Virus Disease 2019(COVID-19). Methods In the epidemic of COVID-19 from January 21 to February 15, 2020, 128 patients with orthopaedic trauma sought emergency treatment at Department of Orthopedic Surgery, The People’s Hospital of Wuhan University. They were 71 males and 57 females with an average age of 48.7 years (from 5 to 88 years).Of them, 107 cases were treated at the outpatient department and 21 hospitalized. Emergency operations were carried out for 4 cases and selective operationsfor 17 cases. COVID-19 infections were recorded in the patients and medical staff as well. Measures taken and experiences learned were summarized since the epidemicoutbreak of COVID-19. Results Of the 107 cases treated at the outpatient department, 3 had a definite diagnosis of COVID-19 and 3 a suspected diagnosis of COVID-19. Of the 4 cases undergoing emergency surgery, one was suspected of having COVID-19. Of the 17 cases undergoing selective surgery, one was diagnosed definitely as COVID-19and 2 were suspected of COVID-19. Two nurses were diagnosed definitely as having mildCOVID-19.One doctor and one nurse were suspected of COVID-19. Since the COVID-19 infections in medical staff occurred all before the preventive and control measures for COVID-19 had been implemented,is was not ruled out that their infections might have come from communities. Conclusions It is particularly important for medical institutions of all levels to maintain safe and effective routine services while doing well in COVID-19 prevention. In the epidemic of COVID-19, front-line medical staff in emergency traumatic orthopedics is faced with great challenges in the process of diagnosing and treating patients. High-quality and safe medical services can be provided as long as nosocomial COVID-19infection is effectively controlled by rigid screening of patientsnewly admitted, classified management of inpatients, optimal management of inpatient wards, standard preventive measures in perioperative period, a perfect system for medical protection, and medical education for patients and their carers.",2020,"YANG, Yue; YU, Aixi; XIAO, Wenxia; SUN, Zhibo; LIU, Feng; WU, Fei",Chinese Journal of Orthopaedic Trauma,2747384503,#2086,
,CZI,Nursing human resource management of infectious disease hospitals under novel coronavirus pneumonia threats,10.1002/job.396,,,,"With the outbreak of novel coronavirus pneumonia, Beijing You'an Hospital has become one of the three infectious disease specialist hospitals designated to treat patients of such pneumonia. Under the premise of comprehensively implementing various emergency treatment tasks and ensuring the normal operation of other wards, the Nursing Department has put in place emergency plans and deployed due manpower for rapid response, timely personnel deployment, and reasonable reserve echelon structure. These measures have been taken as required by the patients’ numbers, critical conditions, disease diagnosis, and the guidelines of treatment and protection. While ensuring the completion of treatment work, we manage to leverage nursing human resources in a scientific, standardized and maximized efficiency manner, to ensure the quality of nursing, and the physical and mental health of nursing staff.",2020,"GUO, Huimin; ZHANG, Lili; YANG, Jiankun; BAO, Zhiying; REN, Zhen",Chinese Journal of Hospital Administration,2015808954,#2271,
,CZI,Medicinal chemistry strategies toward host targeting antiviral agents,10.1002/med.21664,,,,"Direct-acting antiviral agents (DAAs) represent a class of drugs targeting viral proteins and have been demonstrated to be very successful in combating viral infections in clinic. However, DAAs suffer from several inherent limitations, including narrow-spectrum antiviral profiles and liability to drug resistance, and hence there are still unmet needs in the treatment of viral infections. In comparison, host targeting antivirals (HTAs) target host factors for antiviral treatment. Since host proteins are probably broadly required for various viral infections, HTAs are not only perceived, but also demonstrated to exhibit broad-spectrum antiviral activities. In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. In this review, we summarize various host proteins as antiviral targets from a medicinal chemistry prospective. Challenges and issues associated with HTAs are also discussed. Abstract Direct-acting antiviral agents (DAAs) represent a class of drugs targeting viral proteins and have been demonstrated to be very successful in combating viral infections in clinic. However, DAAs suffer from several inherent limitations, including narrow-spectrum antiviral profiles and liability to drug resistance, and hence there are still unmet needs in the treatment of viral infections. In comparison, host targeting antivirals (HTAs) target host factors for antiviral treatment. Since host proteins are probably broadly required for various viral infections, HTAs are not only perceived, but also demonstrated to exhibit broad-spectrum antiviral activities. In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. In this review, we summarize various host proteins as antiviral targets from a medicinal chemistry prospective. Challenges and issues associated with HTAs are also discussed.",2020,"Ji, Xingyue; Li, Zhuorong",Medicinal Research Reviews,3006259301,#971,
,CZI,In Case You Haven't Heard…,10.1002/mhw.32253,,,,"China reported a major drop in new coronavirus cases to 2,641 on Feb. 15, a decline after Chinese officials began implementing measures to contain the illness, and a slight increase in new deaths to 143, Fox News reported Feb. 16. The new figures bring the total number of deaths from the virus, now known as COVID-19, to 1,523 globally, and there are 66,492 confirmed cases in the country, according to China's National Health Commission. The outbreak has taxed health care workers, doctors and nurses throughout China, particularly in Wuhan, where it first originated in December 2019. Robots have been deployed in some hospitals to deliver medicines and disinfect surfaces so workers are free to do other tasks. Survivors of the outbreak in China could face a mental health toll after weeks of being quarantined from the rest of the world, which could create anxiety and fear, according to some mental health professionals.",2020,,Mental Health Weekly,,#1710,
,CZI,Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults,10.1002/ppul.24718,,,,"Abstract Purpose To discuss the different characteristics of clinical, laboratory, and chest computed tomography (CT) in pediatric patients from adults with 2019 novel coronavirus (COVID-19) infection. Methods The clinical, laboratory, and chest CT features of 20 pediatric inpatients with COVID-19 infection confirmed by pharyngeal swab COVID-19 nucleic acid test were retrospectively analyzed during 23 January and 8 February 2020. The clinical and laboratory information was obtained from inpatient records. All the patients were undergone chest CT in our hospital. Results Thirteen pediatric patients (13/20, 65%) had an identified history of close contact with COVID-19 diagnosed family members. Fever (12/20, 60%) and cough (13/20, 65%) were the most common symptoms. For laboratory findings, procalcitonin elevation (16/20, 80%) should be pay attention to, which is not common in adults. Coinfection (8/20, 40%) is common in pediatric patients. A total of 6 patients presented with unilateral pulmonary lesions (6/20, 30%), 10 with bilateral pulmonary lesions (10/20, 50%), and 4 cases showed no abnormality on chest CT (4/20, 20%). Consolidation with surrounding halo sign was observed in 10 patients (10/20, 50%), ground-glass opacities were observed in 12 patients (12/20, 60%), fine mesh shadow was observed in 4 patients (4/20, 20%), and tiny nodules were observed in 3 patients (3/20, 15%). Conclusion Procalcitonin elevation and consolidation with surrounding halo signs were common in pediatric patients which were different from adults. It is suggested that underlying coinfection may be more common in pediatrics, and the consolidation with surrounding halo sign which is considered as a typical sign in pediatric patients.",2020,"Xia, Wei; Shao, Jianbo; Guo, Yu; Peng, Xuehua; Li, Zhen; Hu, Daoyu",Pediatric Pulmonology,2340258942,#4404,
,CZI,Novel coronavirus infection and pregnancy,10.1002/uog.22006,,,,"Clinical manifestation of COVID-19 infection during pregnancy Due to the physiological changes in their immune and cardiopulmonary systems, pregnant women are more likely to develop severe illness after infection with respiratory viruses. In 2009, pregnant women accounted for 1% of patients infected with influenza A subtype H1N1 virus, but they accounted for 5% of all H1N1-related deaths6. In addition, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), two notable strains of the coronavirus family, are both known to be responsible for severe complications during pregnancy, including the need for endotracheal intubation, admission to an intensive care unit (ICU), renal failure and death7, 8. Interestingly, the impact of COVID-19 infection on pregnant women appears to be less severe. Chen et al.9 reported the clinical characteristics of nine pregnant women with laboratory-confirmed COVID-19 in the third trimester, which comprised mainly fever and cough. Other symptoms included myalgia, malaise, sore throat, diarrhea and shortness of breath. Data from laboratory tests showed that the majority of patients had lymphopenia and increased C-reactive protein, and chest CT scans showed multiple patchy ground-glass shadows in the lungs. Pregnancy complications that appeared after the onset of COVID-19 infection included fetal distress in two of nine patients and premature rupture of the membranes in two of nine patients. None of the patients developed severe COVID-19 pneumonia or died. Another series10 of nine pregnant women with COVID-19 pneumonia presenting from mid-trimester onwards, or during the postpartum period, reported similar findings except for one woman requiring ICU care and ventilation for acute respiratory distress syndrome after the infection was diagnosed 2?days postpartum. In general, both studies reported that the clinical characteristics of the pregnant women with COVID-19 pneumonia were similar to those of non-pregnant adult patients who developed COVID-19 pneumonia2-4. These observations are also in line with what has been learned about COVID-19 pneumonia in pregnancy in several other hospitals in Wuhan, China. Pregnant healthcare professionals should follow risk-assessment and infection-control guidelines following exposure to patients with suspected or confirmed COVID-19. Adherence to recommended infection prevention and control practices is an important part of protecting all healthcare professionals in clinical settings11.",2020,"Yang, H.; Wang, C.; Poon, L. C.",Ultrasound in Obstetrics & Gynecology,3005679569,#4390,
,CZI,Histopathologic Evaluation and Scoring of Viral Lung Infection,10.1007/978-1-0716-0211-9_16,,31883098,,"Emergent coronaviruses such as MERS-CoV and SARS-CoV can cause significant morbidity and mortality in infected individuals. Lung infection is a common clinical feature and contributes to disease severity as well as viral transmission. Animal models are often required to study viral infections and therapies, especially during an initial outbreak. Histopathology studies allow for identification of lesions and affected cell types to better understand viral pathogenesis and clarify effective therapies. Use of immunostaining allows detection of presumed viral receptors and viral tropism for cells can be evaluated to correlate with lesions. In the lung, lesions and immunostaining can be qualitatively described to define the cell types, microanatomic location, and type of changes seen. These features are important and necessary, but this approach can have limitations when comparing treatment groups. Semiquantitative and quantitative tissue scores are more rigorous as these provide the ability to statistically compare groups and increase the reproducibility and rigor of the study. This review describes principles, approaches, and resources that can be useful to evaluate coronavirus lung infection, focusing on MER-CoV infection as the principal example.",2020,"Meyerholz, David K.; Beck, Amanda P.","Methods in molecular biology (Clifton, N.J.)",2996797247,#3837,
,CZI,Deducing the Crystal Structure of MERS-CoV Helicase,10.1007/978-1-0716-0211-9_6,,31883088,,"RNA virus encodes a helicase essential for viral RNA transcription and replication when the genome size is larger than 7kb. Coronavirus (CoV) has an exceptionally large RNA genome (~30kb) and it encodes an essential replicase, the nonstructural protein 13 (nsp13), a member of superfamily 1 helicases. Nsp13 is among the evolutionary most conserved proteins not only in CoVs but also in nidovirales. Thus, it is considered as an important drug target. However, the high-resolution structure of CoV nsp13 remained unavailable even until more than a decade after the outbreak of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, which hindered the structure-based drug design. This is in part due to the intrinsic flexibility of nsp13. Here, we describe protocols of deducing the crystal structure of Middle East respiratory syndrome coronavirus (MERS-CoV) helicase in detail, which include protein expression, purification, crystallization, enzymatic characterization, and structure determination. With these methods, catalytically active recombinant MERS-CoV nsp13 protein can be prepared and crystallized and the crystal structure can be solved.",2020,"Cui, Sheng; Hao, Wei","Methods in molecular biology (Clifton, N.J.)",2997961760,#4045,
,CZI,Antigen Capture Enzyme-Linked Immunosorbent Assay for Detecting Middle East Respiratory Syndrome Coronavirus in Humans,10.1007/978-1-0716-0211-9_7,,31883089,,"The Middle East respiratory syndrome (MERS) is the second novel zoonotic disease infecting humans caused by coronavirus (CoV) in this century. To date, more than 2200 laboratory-confirmed human cases have been identified in 27 countries, and more than 800 MERS-CoV associated deaths have been reported since its outbreak in 2012. Rapid laboratory diagnosis of MERS-CoV is the key to successful containment and prevention of the spread of infection. Though the gold standard for diagnosing MERS-CoV infection in humans is still nucleic acid amplification test (NAAT) of the up-E region, an antigen capture enzyme-linked immunosorbent assay (ELISA) could also be of use for early diagnosis in less developed locations. In the present method, a step-by-step guide to perform a MERS-CoV nucleocapsid protein (NP) capture ELISA using two NP-specific monoclonal antibodies is provided for readers to develop their in-house workflow or diagnostic kit for clinical use and for mass-screening project of animals (e.g., dromedaries and bats) to better understand the spread and evolution of the virus.",2020,"Fung, J.; Lau, S. K. P.; Woo, P. C. Y.","Methods in molecular biology (Clifton, N.J.)",2997407711,#36,
,CZI,SARS-CoV-2: a potential novel etiology of fulminant myocarditis,10.1007/s00059-020-04909-z,,,,,2020,"Chen, Chen; Zhou, Yiwu; Wang, Dao Wen",Herz,,#4609,
,CZI,Critical care management of adults with community-acquired severe respiratory viral infection,10.1007/s00134-020-05943-5,,,,"With the expanding use of molecular assays, viral pathogens are increasingly recognized among critically ill adult patients with community-acquired severe respiratory illness; studies have detected respiratory viral infections (RVIs) in 17–53% of such patients. In addition, novel pathogens including zoonotic coronaviruses like the agents causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019 nCoV) are still being identified. Patients with severe RVIs requiring ICU care present typically with hypoxemic respiratory failure. Oseltamivir is the most widely used neuraminidase inhibitor for treatment of influenza; data suggest that early use is associated with reduced mortality in critically ill patients with influenza. At present, there are no antiviral therapies of proven efficacy for other severe RVIs. Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti-influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs. Evidence-based supportive care is the mainstay for management of severe respiratory viral infection. Non-invasive ventilation in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is associated with a high likelihood of transition to invasive ventilation. Limited existing knowledge highlights the need for data regarding supportive care and adjunctive pharmacologic therapy that is specific for critically ill patients with severe RVI. There is a need for more pragmatic and efficient designs to test different therapeutics both individually and in combination.",2020,"Arabi, Yaseen M.; Fowler, Robert; Hayden, Frederick G.",Intensive Care Medicine,3005617185,#684,
,CZI,COVID-19: a novel coronavirus and a novel challenge for critical care,10.1007/s00134-020-05955-1,,32125458,,,2020,"Arabi, Yaseen M.; Murthy, Srinivas; Webb, Steve",Intensive Care Med,3006207556,#3461,
,CZI,How to face the novel coronavirus infection during the 2019–2020 epidemic: the experience of Sichuan Provincial People’s Hospital,10.1007/s00134-020-05964-0,,,,"January 17, 2020: the Sichuan Provincial People’s Hospital officially launched the 2019 influenza emergency response plan and established a leading group for influenza prevention and control. The president of Sichuan Provincial People’s Hospital serves as the team leader, and its members include related departments such as the administrative department, the intensive care unit, the infectious disease department, the respiratory department, nurses, the nosocomial infection control department and the radiology department. Afterwards we established multiple working groups: the emergency team, the prevention and control team, the medical emergency team, the material security team, the publicity and education team and the information updating team. Since the transmission dynamics were unclear, establishing fever clinics, isolation wards and emergency wards were the most important measures.JO - Intensive Care Medicine",2020,"Pan, Lingai; Wang, Li; Huang, Xiaobo",,,#1122,
,CZI,Intensive care during the coronavirus epidemic,10.1007/s00134-020-05966-y,,,,"As a response to the epidemic, the local government had appointed several designated hospitals for patients with SARS-CoV-2 infection. Despite a common coping strategy for mass casualty (earthquake and blast injury) in China, SARI epidemic has proposed a new challenge for healthcare workers, especially intensivists. About 15–20% of suspected and confirmed patients with SARS-CoV-2 infection in fever clinics developed severe hypoxemia (since the second week of disease course), and required some form of ventilatory support such as high-flow nasal cannula, and non-invasive and invasive mechanical ventilation. In addition, other complications might occur, including, but not limited to, shock, acute kidney injury, gastrointestinal bleeding, and rhabdomyolysis. No antiviral agents have been proven to be effective against the coronavirus. Therefore, management of critically ill patients with SARS-CoV-2 infection still remains supportive rather than definitive, indicating remarkable workload for intensive care physicians and nurses. This surge of critically ill patients in designated hospitals as well as fever clinics represents urgent demands for intensive care with regards to space, supplies, and staff (Table 1) [5,6,7,8]. Response to these demands requires cooperation between the medical rescue team, infection control specialists, local health authorities, and center for disease control and prevention [9].ER -",2020,"Qiu, Haibo; Tong, Zhaohui; Ma, Penglin; Hu, Ming; Peng, Zhiyong; Wu, Wenjuan; Du, Bin; China Critical Care Clinical Trials, Group",Intensive Care Medicine,2531638709,#1780,
,CZI,Severe SARS-CoV-2 infections: practical considerations and management strategy for intensivists,10.1007/s00134-020-05967-x,,,,"Etiological agent and epidemiology The new agent causing this pneumonia, a coronavirus (SARS-CoV-2), was identified and sequenced [3] and diagnostic tests were developed [4]. On January 30, 2020, the World Health Organization issued a worldwide public health alert on the emergence of a new epidemic viral disease. On February 3, 2020, 17,391 confirmed cases (153 cases outside of China) have been reported (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/). The overall mortality rate of affected patients is difficult to assess at this time, because of the lack of a reliable denominator. Severe forms represent 14% of the reported cases, and the overall mortality is around 2% of the confirmed cases. To date, 153 cases have been reported in 23 countries outside China (overall, 24 cases in Europe), most of them being imported cases: tourists coming from China, or China-originating persons returning to their country of residence after traveling to visit family in Wuhan or other Chinese regions. In Europe, at least three cases in Germany and one case in France involved patients with no history of travel to China. The German case occurred after exposure to an asymptomatic contact coming from China [5].AU - Lucet, Jean-Christophe",2020,"Bouadma, Lila; Lescure, Francois-Xavier; Yazdanpanah, Yazdan; Timsit, Jean-Francois",Intensive Care Medicine,1780890786,#2356,
,CZI,"The novel coronavirus (SARS-CoV-2) infections in China: prevention, control and challenges",10.1007/s00134-020-05977-9,,,,"Since December 2019, an outbreak of novel coronavirus (SARS-CoV-2) that began from Wuhan, Hubei Province, has rapidly spread to 34 provincial-level divisions of China [1] and 25 countries around the world [2]. Up to February 15, 2020, 68,586 cases in China and 526 cases in other countries have been identified as having COVID-19 (eFigure 1). The estimated mortality rate is 3.1% in Wuhan, 2.8% in Hubei Province, 0.6% in other provinces of China, 2.4% in China and 0.4% in other countries, respectively. Faced with such a grim situation, the Chinese government has taken a series of unprecedented rigorous measures. First, all the 31 provincial-level divisions in China mainland have launched the highest level of responding mechanism for major public health emergency. Second, Wuhan and other 12 cities in Hubei Province have consecutively shut down all outbound transportation channels and suspended public transportation. Third, the State Council announced that both the Spring Festival holiday and winter vacation will be extended. Fourth, two emergency makeshift hospitals (Huoshenshan and Leishenshan hospitals) with a total capacity of 2600 beds were built and more than ten cabin hospitals were renovated with more than 10,000 beds in Wuhan. Fifth, more than 30,000 members from military and public hospitals have successively headed out to Wuhan and other cities in Hubei Province.ER -",2020,"Zhang, Sheng; Diao, Meng Yuan; Duan, Liwei; Lin, Zhaofen; Chen, Dechang",Intensive Care Medicine,3006332573,#3024,
,CZI,Challenges and countermeasures for organ donation during the SARS-CoV-2 epidemic: the experience of Sichuan Provincial People’s Hospital,10.1007/s00134-020-05978-8,,,,"Up to 09:40 February 17, 2020, there have been 70,640 confirmed SARS-CoV-2 (aka 2019-nCoV) cases in China. Sichuan Provincial People’s Hospital acts as an organ transplant center in west of China, approximately 200 solid organ transplants performed each year and can perform heart, lung, liver, kidney, small bowel, stem cell transplantation, so it is necessary to establish a hospital-specific protocol to deal with the SARS-CoV-2 infection for the donor and recipient.",2020,"Pan, Lingai; Zeng, Jie; Yang, Hongji",Intensive Care Medicine,,#1954,
,CZI,Critical care crisis and some recommendations during the COVID-19 epidemic in China,10.1007/s00134-020-05979-7,,,,"Lack of critical care resource in face of COVID-19 epidemics Based on data reported by the National Health Commission of China, there have been about 2000 new confirmed cases and?>?4000 suspected cases daily over the past week in Wuhan [3]. About 15% of the patients have developed severe pneumonia, and about 6% need noninvasive or invasive ventilatory support. Currently, there are about 1000 patients who need ventilatory support and another 120 new patients daily who require noninvasive or invasive ventilation support in Wuhan city; however, there are only about 600 ICU beds [4]. To address this shortfall, 70 ICU beds were created from general beds and the government quickly transformed three general hospitals to critical care hospitals with a total of about 2500 beds that specialize in patients with severe SARS-CoV-2 pneumonia (equipped with monitors and high-flow nasal cannula, noninvasive ventilator or invasive ventilators). An equally great (or potentially greater) problem is the shortage of trained personnel to treat these critically ill patients. Until the crisis, there were about 300 ICU physicians and 1000 ICU nurses in Wuhan city. By the end of January, more than 600 additional ICU doctors and 1500 ICU nurses were transferred to Wuhan from the rest of China. As well, an additional 3000 staff including infectious disease, respiratory, internal medicine physicians and nurses were transferred to Wuhan by the government. There are logistical issues which make care of the patients difficult. These include donning of personal protective equipment (e.g., gloves, gowns, respiratory and eye protection), lack of instruments and disposables, and shortages of supplemental oxygen. Many severe hypoxemic patients only receive high-flow nasal oxygen (HFNO) or noninvasive mechanical ventilation rather than invasive mechanical ventilation because of intubation delay or lack of mechanical ventilators (especially at early phase). Our preliminary data show that only about 25% of patients who died were intubated and received mechanical ventilation.JO - Intensive Care Medicine",2020,"Xie, Jianfeng; Tong, Zhaohui; Guan, Xiangdong; Du, Bin; Qiu, Haibo; Slutsky, Arthur S.",,2615040641,#3097,
,CZI,Clinical features and short-term outcomes of 18 patients with corona virus disease 2019 in intensive care unit,10.1007/s00134-020-05987-7,,,,,2020,"Cao, Jianlei; Hu, Xiaoyong; Cheng, Wenlin; Yu, Lei; Tu, Wen-Jun; Liu, Qiang",Intensive Care Medicine,2392835677,#3449,
,CZI,"Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China",10.1007/s00134-020-05991-x,,32125452,,,2020,"Ruan, Qiurong; Yang, Kun; Wang, Wenxia; Jiang, Lingyu; Song, Jianxin",Intensive Care Med,2997099310,#3311,
,CZI,Proposal for detection of 2019-nCoV nucleic acid in clinical laboratories,10.1007/s00246-015-1290-6,,,,"In December, the outbreak of a novel coronavirus (2019-nCoV) in Wuhan, China, has attracted extensive global attention. On January 20, 2020,the Chinese health authorities upgraded the coronavirus to a Class B infectious disease in the Law of the People's Republic of China on the Prevention and Treatment of Infectious Diseases , and considered it as Class A infectious diseases in disease control and prevention. On January 22, 2020, the 2019-nCoV nucleic acid detection test was listed as the diagnostic criteria in the 'guidelines for diagnosis and treatment of pneumonia due to 2019-nCoV (Trial Version 2)' . Therefore, standardizing the operation process of the 2019-nCoV nucleic acid detection in clinical laboratories has become a top priority. It is of paramount importance to establish standard protocols for detection of the 2019-nCoV nucleic acids in clinical laboratories to improve the reliability of the results and ensure the biosafety of laboratory personnel.",2020,"TONG, Yongqing",Chinese Journal of Laboratory Medicine,2253369457,#2145,
,CZI,Imaging features of 2019 novel coronavirus pneumonia,10.1007/s00259-020-04720-2,,,,,2020,"Xu, Xi; Yu, Chengcheng; Zhang, Lieguang; Luo, Liangping; Liu, Jinxin",European Journal of Nuclear Medicine and Molecular Imaging,3006313342,#870,
,CZI,(18)F-FDG PET/CT findings of COVID-19: a series of four highly suspected cases,10.1007/s00259-020-04734-w,,32088847,,"PURPOSE: The aim of this case series is to illustrate the (18)F-FDG PET/CT findings of patients with acute respiratory disease caused by COVID-19 in Wuhan, Hubei province of China. METHODS: We describe the (18)F-FDG PET/CT results from four patients who were admitted to the hospital with respiratory symptoms and fever between January 13 and January 20, 2020, when the COVID-19 outbreak was still unrecognized and the virus infectivity was unknown. A retrospective review of the patients' medical history, clinical and laboratory data, as well as imaging findings strongly suggested a diagnosis of COVID-19. RESULTS: All patients had peripheral ground-glass opacities and/or lung consolidations in more than two pulmonary lobes. Lung lesions were characterized by a high (18)F-FDG uptake and there was evidence of lymph node involvement. Conversely, disseminated disease was absent, a finding suggesting that COVID-19 has pulmonary tropism. CONCLUSIONS: Although (18)F-FDG PET/CT cannot be routinely used in an emergency setting and is generally not recommended for infectious diseases, our pilot data shed light on the potential clinical utility of this imaging technique in the differential diagnosis of complex cases.",2020,"Qin, Chunxia; Liu, Fang; Yen, Tzu-Chen; Lan, Xiaoli",Eur J Nucl Med Mol Imaging,2316423350,#1781,
,CZI,Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2,10.1007/s00259-020-04735-9,,,,"The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2, also called 2019-nCoV) recently break out in Wuhan, China, and was named as COVID-19. With the spread of the disease, similar cases have also been confirmed in other regions of China. We aimed to report the imaging and clinical characteristics of these patients infected with SARS-CoV-2 in Guangzhou, China.",2020,"Xu, Xi; Yu, Chengcheng; Qu, Jing; Zhang, Lieguang; Jiang, Songfeng; Huang, Deyang; Chen, Bihua; Zhang, Zhiping; Guan, Wanhua; Ling, Zhoukun; Jiang, Rui; Hu, Tianli; Ding, Yan; Lin, Lin; Gan, Qingxin; Luo, Liangping; Tang, Xiaoping; Liu, Jinxin",European Journal of Nuclear Medicine and Molecular Imaging,3001118548,#2504,
,CZI,Standardized diagnosis and treatment of colorectal cancer during the outbreak of novel coronavirus pneumonia in Renji hospital,10.1007/s002689900293,,,,"Novel coronavirus pneumonia (NCP) is currently raging in China. It has been proven that NCP can be transmitted from human to human and cause hospital infection, which seriously threatens surgical staffs and inpatients. Although colorectal surgery is not a front-line subject in the fight against the epidemic, but in this special situation, now it is a difficult task that with the premise of how to maximize the protection for patients and their families, health of medical staff, and the safety of wards and hospitals, we can provide the highest quality medical services to ensure the orderly development of previous clinical work. Referring to the "Diagnosis and Treatment Scheme for NCP (Trial Version 4 and 5)" and combining the actual practice situation in our hospital with the "Summary of New Coronavirus Files of Shanghai Renji Hospital", we summarize how to carry out the clinical practice of colorectal surgery under the situation of the prevention and control of the NCP epidemiology, meanwhile under such situation aiming the procedure of diagnose and treatment for emergency patients with colorectal tumor, we share the experiences of the diagnosis of colorectal tumor, the management of patients with colorectal cancer who are scheduled to be admitted for surgery, the protection of wards, the perioperative management. More importantly, we introduce in detail the operative management and perioperative management of colorectal surgery patients suspected or diagnosed with new coronary pneumonia, including prevention and control measures for medical staff, operating rooms and surgical instruments. The main points are as follows: (1) Multidisciplinary team (MDT) must be run through the diagnosis and treatment of colorectal cancer. The members include not only routine departments, but also respiratory department and infectious department. (2) Colonoscopy examination may cause cross infection of NCP to patients and doctors. Therefore, it is prior to examine the emergency cases and life-threatening patients (bleeding, obstruction, gastrointestinal foreign bodies, etc.). If the emergent patients (intestinal obstruction) with suspected or confirmed NCP, the surgeons must perform emergency surgery, and intestinal decompressive tube through colonoscopy is not recommended. (3) The colorectal cancer patients with suspected or confirmed NCP should be placed in the isolated room with separate medical devices, and the operative room with negative pressure (under-5 Pa) must be separated. All disposable medical items, body fluids and feces of the patients in perioperative periods must be unified disposed according to the medical waste standard. (4) The surgical medical workers who process colorectal cancer patients with NCP must be protected by three-level. After operation, the medical workers must receive medical observation and be isolated for 14 days. We hope our "Renji experience" will be beneficial to colleagues.",2020,"LUO, Yang; ZHONG, Ming",Chinese Journal of Gastrointestinal Surgery,2009124022,#1958,
,CZI,"Old Threat, New Enemy: Is Your Interventional Radiology Service Ready for the Coronavirus Disease 2019?",10.1007/s00270-020-02440-6,,32103304,,,2020,"Da Zhuang, Kun; Tan, Bien Soo; Tan, Ban Hock; Too, Chow Wei; Tay, Kiang Hiong",Cardiovascular and interventional radiology,2070556329,#4046,
,CZI,Imaging changes in patients with 2019-nCov,10.1007/s00330-020-06713-z,,,,,2020,"Pan, Yueying; Guan, Hanxiong",European Radiology,3004780338,#288,
,CZI,"Initial CT findings and temporal changes in patients with the novel coronavirus pneumonia (2019-nCoV): a study of 63 patients in Wuhan, China",10.1007/s00330-020-06731-x,,,,The purpose of this study was to observe the imaging characteristics of the novel coronavirus pneumonia.,2020,"Pan, Yueying; Guan, Hanxiong; Zhou, Shuchang; Wang, Yujin; Li, Qian; Zhu, Tingting; Hu, Qiongjie; Xia, Liming",European Radiology,3006354146,#869,
,CZI,Outbreak of novel coronavirus (COVID-19): What is the role of radiologists?,10.1007/s00330-020-06748-2,,,,• Novel coronavirus (COVID-19)-infected pneumonia usually manifests as bilateral ground-glass opacities in the lung periphery on chest CT scans.,2020,"Kim, Hyungjin",European Radiology,3005943294,#1223,
,CZI,The 2019 novel cornoavirus pneumonia with onset of oculomotor nerve palsy: a case study,10.1007/s00415-020-09773-9,,,,"On December 31, 2019, several cases of pneumonia of unknown etiology have been reported in Wuhan, Hubei province, China [1,2,3]. On January 7, 2020, Chinese health authorities confirmed that these cases were associated with a novel coronavirus, which was subsequently named 2019nCoV by WHO [4]. Previous study [5] reported that virus infection can cause several neurological complications, including polyneuritis, Guillain–Barre syndrome (GBS), meningitis, encephalomyelitis, and encephalopathy. We describe a rare case of 2019-CoV infection and acute unilateral isolated oculomotor nerve palsy. In this case, the diagnosis was made based on the chest computed CT manifestations and throat swab sample test. A 62-year-old man was admitted to our department with a 5-day history of persistent diplopia and a droopy left eyelid. During initial hospital assessment, he endorsed limb weakness and poor spirit. He denied any fever, neck stiffness, headache, cough, shortness of breath, chest pain, or photophobia. He had a history of alcohol and tobacco use, type II diabetes mellitus and hypertension (both well controlled by drugs), and lacunar infarction (without sequela).DA - 2020/02/25",2020,"Wei, Heng; Yin, Hongxiang; Huang, Min; Guo, Zhenli",Journal of Neurology,2758126530,#1918,
,CZI,Stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from Hong Kong,10.1007/s00417-020-04641-8,,,,Coronavirus disease (COVID-19) has rapidly emerged as a global health threat. The purpose of this article is to share our local experience of stepping up infection control measures in ophthalmology to minimise COVID-19 infection of both healthcare workers and patients.,2020,"Lai, Tracy H. T.; Tang, Emily W. H.; Chau, Sandy K. Y.; Fung, Kitty S. C.; Li, Kenneth K. W.",Graefe's Archive for Clinical and Experimental Ophthalmology,3004790666,#3156,
,CZI,Development of an indirect ELISA for detecting porcine deltacoronavirus IgA antibodies,10.1007/s00705-020-04541-6,,32052195,,"Porcine deltacoronavirus (PDCoV) is a novel coronavirus that can cause vomiting and watery diarrhea in pigs and death in piglets. Since PDCoV was first detected in 2009 in Hong Kong, the prevalence of PDCoV has increased in recent years, resulting in serious economic losses to the swine industry. The coronavirus spike (S) protein is an antigen that has been demonstrated to contain epitopes that induce neutralizing antibodies. The presence of serum and milk IgA antibodies against pathogens that replicate primarily on mucosal surfaces is important for mucosal immunity. Here, an indirect anti-PDCoV IgA antibody enzyme-linked immunosorbent assay (PDCoV S1 IgA ELISA) using the purified S1 portion of S protein as the coating antigen was developed to detect PDCoV IgA antibodies in serum and sow's milk. A receiver operating characteristic (ROC) curve analysis showed high specificity and sensitivity of the PDCoV-S1-IgA-ELISA based on samples confirmed by IFA. Anti-PDCoV IgA antibodies in 152 serum samples and 65 milk samples collected from six farms that had experienced diarrhea outbreaks within previous last two years were detected by this assay, and 62.5% of the serum samples and 100% of the milk samples were positive for PDCoV. The indirect ELISA method established in this study will provide a convenient tool for measurement of serum and milk IgA levels against PDCoV in pig herds, rapid detection of PDCoV infection in pigs, and evaluation of the immunogenicity of vaccines.",2020,"Lu, Manman; Liu, Qiuge; Wang, Xiaobo; Zhang, Jialin; Zhang, Xin; Shi, Da; Liu, Jianbo; Shi, Hongyan; Chen, Jianfei; Feng, Li",Arch Virol,3006146227,#877,
,CZI,Coronavirus COVID-19 impacts to dentistry and potential salivary diagnosis,10.1007/s00784-020-03248-x,,32078048,,,2020,"Sabino-Silva, Robinson; Jardim, Ana Carolina Gomes; Siqueira, Walter L.",Clin Oral Investig,2141065236,#1504,
,CZI,"Public awareness of coronavirus in Al-Jouf region, Saudi Arabia",10.1007/s10389-020-01209-y,,,,"Since 2012 and to date, outbreak/new cases of Middle East respiratory syndrome-related coronavirus (MERS-CoV) were always reported in Saudi Arabia. Al-Jouf region is considered as one of the most vulnerable areas to the disease outbreak. This research aimed to assess (to the best of our knowledge), for the first time, the current level of awareness towards MERS-CoV among the Al-Jouf region population through a well-designed multistage questionnaire.",2020,"Nooh, Hanaa Zakaria; Alshammary, Rawan Humaidy; Alenezy, Jomanh Mohammed; Alrowaili, Njood Hial; Alsharari, Amani Jaded; Alenzi, Njood Menwer; Sabaa, Hanan E.",Journal of Public Health,3006484532,#1794,
,CZI,Containing 2019-nCoV (Wuhan) coronavirus,10.1007/s10729-020-09504-6,,,,"The novel coronavirus 2019-nCoV first appeared in December 2019 in Wuhan, China. While most of the initial cases were linked to the Huanan Seafood Wholesale Market, person-to-person transmission has been verified. Given that a vaccine cannot be developed and deployed for at least a year, preventing further transmission relies upon standard principles of containment, two of which are the isolation of known cases and the quarantine of persons believed at high risk of exposure. This note presents probability models for assessing the effectiveness of case isolation and quarantine within a community during the initial phase of an outbreak with illustrations based on early observations from Wuhan.",2020,"Kaplan, Edward H.",Health Care Management Science,3004824173,#4764,
,CZI,The Role of Augmented Intelligence (AI) in Detecting and Preventing the Spread of Novel Coronavirus,10.1007/s10916-020-1536-6,,,,"The 2019-nCov will not be the last epidemic to challenge public health experts. The growth of AI-driven techniques to identify epidemiologic risks early will be key to our improvement of prediction, prevention, and detection of future global health risks. The devastating situation in Wuhan, China and future epidemics will also find value in ongoing research in 2019-nCov case detection, spread prediction, treatment effectiveness, and containment. The wide variety, velocity, and veracity of data now available in crises yield data sets that many researchers will now need to incorporate into evermore complex models. This requires expansion of talent within AI for healthcare applications. AI is no longer a niche research area nor is it a tool for the most advanced healthcare systems only, its global impact on healthcare is real and its potential to save lives in this epidemic as well as future epidemics should not be underestimated. It is critical to the global health of all humankind for the scientific community to embrace AI and leverage its power in securing our collective future.ER -",2020,"Long, Justin B.; Ehrenfeld, Jesse M.",Journal of Medical Systems,3005084260,#299,
,CZI,Antivirals in medical biodefense,10.1007/s11262-020-01737-5,,,,"The viruses historically implicated or currently considered as candidates for misuse in bioterrorist events are poxviruses, filoviruses, bunyaviruses, orthomyxoviruses, paramyxoviruses and a number of arboviruses causing encephalitis, including alpha- and flaviviruses. All these viruses are of concern for public health services when they occur in natural outbreaks or emerge in unvaccinated populations. Recent events and intelligence reports point to a growing risk of dangerous biological agents being used for nefarious purposes. Public health responses effective in natural outbreaks of infectious disease may not be sufficient to deal with the severe consequences of a deliberate release of such agents. One important aspect of countermeasures against viral biothreat agents are the antiviral treatment options available for use in post-exposure prophylaxis. These issues were adressed by the organizers of the 16th Medical Biodefense Conference, held in Munich in 2018, in a special session on the development of drugs to treat infections with viruses currently perceived as a threat to societies or associated with a potential for misuse as biothreat agents. This review will outline the state-of-the-art methods in antivirals research discussed and provide an overview of antiviral compounds in the pipeline that are already approved for use or still under development.",2020,"Bugert, J. J.; Hucke, F.; Zanetta, P.; Bassetto, M.; Brancale, A.",Virus Genes,2728328470,#1327,
,CZI,Physikalischer Schutz vor respiratorischen Viren,10.1007/s11298-020-7917-9,,,,"Durch die Bildung eines Films auf den Zellen der Nasenschleimhaut kann ein Spray dabei helfen, sich vor Erkältungsviren zu schützen. Der aus Rotalgen gewonnene Wirkstoff Carragelose bildet eine physikalische Barriere auf der Nasenschleimhaut, in der sich respiratorische Viren - darunter auch humane Coronaviren - verfangen. So wird der Kontakt zwischen ihnen und menschlichen Zellen weitestgehend unterbunden und der weitere Infektionsweg deutlich erschwert. In klinischen Studien an Patienten mit viral bedingten grippalen Infekten konnte gezeigt werden, dass Carragelose-haltige Sprays zur Anwendung in der Nase (wie algovir Effekt) die Viruslast nach drei bis vier Behandlungstagen um mehr als 90% reduzieren können. Getestet wurde die Wirksamkeit des Wirkstoffs unter anderem an verschiedenen Typen humaner Coronaviren - jedoch nicht an dem Coronavirus SARS-CoV-2. Daher können derzeit keine endgültigen Rückschlüsse zur Aktivität und Effektivität des Wirkstoffs gegen 2SARS-CoV-2 gezogen werden. Allerdings haben Carragelose-Erkältungssprays ein ausgezeichnetes Sicherheitsprofil, weshalb sie durchaus ergänzend zu den gängigen Maßnahmen zum Schutz vor respiratorischen Viren wie Händedesinfektion und Mundschutz angewendet und den Apothekenkunden empfohlen werden können. AU - API, Redaktion",2020,,CME,2168055967,#3470,
,CZI,Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission,10.1007/s11427-020-1637-5,,32009228,,,2020,"Xu, Xintian; Chen, Ping; Wang, Jingfang; Feng, Jiannan; Zhou, Hui; Li, Xuan; Zhong, Wu; Hao, Pei",Sci China Life Sci,2999364275,#253,
,CZI,Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury,10.1007/s11427-020-1643-8,,,,"The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.",2020,"Liu, Yingxia; Yang, Yang; Zhang, Cong; Huang, Fengming; Wang, Fuxiang; Yuan, Jing; Wang, Zhaoqin; Li, Jinxiu; Li, Jianming; Feng, Cheng; Zhang, Zheng; Wang, Lifei; Peng, Ling; Chen, Li; Qin, Yuhao; Zhao, Dandan; Tan, Shuguang; Yin, Lu; Xu, Jun; Zhou, Congzhao; Jiang, Chengyu; Liu, Lei",Science China Life Sciences,3005655936,#693,
,CZI,Bat origin of a new human coronavirus: there and back again,10.1007/s11427-020-1645-7,,,,,2020,"Li, Xiang; Song, Yuhe; Wong, Gary; Cui, Jie",Science China Life Sciences,3006649197,#697,
,CZI,Clinical trials for the treatment of Coronavirus disease 2019 (COVID-19): A rapid response to urgent need,10.1007/s11427-020-1660-2,,,,"Clinical trial for COVID-19 was first registered on January 23, 2020. In the last few weeks, an escalating number of clinical trials has been planned and registered with ongoing investigations taking place. From the Chinese Clinical Trial Registry (http://www.chictr.org.cn) and U.S. National Library of Medicine Clinical Trial Registry (https://clinicaltrials. gov), there are 125 clinical trials registered by February 18, 2020, focusing on the treatment of COVID-19. There is an upward trend on the number of registered clinical trials (Figure 1). Among the 125 clinical trials on treatment, 33.3% used anti-viral agents, 14.7% anti-inflammation or immunomodulators, 33.3% herbs or traditional Chinese medicine (TCM), 9.3% cell-based therapy, 2.3% antioxidation and 7.0% other approaches. Pharmaceutical companies, government, institutions, physicians and scientists are the main force behind these researches. 17 years ago (2003), SARS affectedAU - Zhang, Tengyue",2020,"He, Yudi; Xu, Wenshuai; Ma, Aiping; Yang, Yanli; Xu, Kai-Feng",Science China Life Sciences,3006394629,#3246,
,CZI,Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19),10.1007/s11606-020-05762-w,,,,"In late December 2019, a cluster of cases with 2019 Novel Coronavirus pneumonia (SARS-CoV-2) in Wuhan, China, aroused worldwide concern. Previous studies have reported epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19). The purpose of this brief review is to summarize those published studies as of late February 2020 on the clinical features, symptoms, complications, and treatments of COVID-19 and help provide guidance for frontline medical staff in the clinical management of this outbreak.",2020,"Jiang, Fang; Deng, Liehua; Zhang, Liangqing; Cai, Yin; Cheung, Chi Wai; Xia, Zhengyuan",Journal of General Internal Medicine,2604381070,#4546,
,CZI,"Can Chinese Medicine Be Used for Prevention of Corona Virus Disease 2019 (COVID-19)? A Review of Historical Classics, Research Evidence and Current Prevention Programs",10.1007/s11655-020-3192-6,,32065348,,"OBJECTIVE: Since December 2019, an outbreak of corona virus disease 2019 (COVID-19) occurred in Wuhan, and rapidly spread to almost all parts of China. This was followed by prevention programs recommending Chinese medicine (CM) for the prevention. In order to provide evidence for CM recommendations, we reviewed ancient classics and human studies. METHODS: Historical records on prevention and treatment of infections in CM classics, clinical evidence of CM on the prevention of severe acute respiratory syndrome (SARS) and H1N1 influenza, and CM prevention programs issued by health authorities in China since the COVID-19 outbreak were retrieved from different databases and websites till 12 February, 2020. Research evidence included data from clinical trials, cohort or other population studies using CM for preventing contagious respiratory virus diseases. RESULTS: The use of CM to prevent epidemics of infectious diseases was traced back to ancient Chinese practice cited in Huangdi's Internal Classic (Huang Di Nei Jing) where preventive effects were recorded. There were 3 studies using CM for prevention of SARS and 4 studies for H1N1 influenza. None of the participants who took CM contracted SARS in the 3 studies. The infection rate of H1N1 influenza in the CM group was significantly lower than the non-CM group (relative risk 0.36, 95% confidence interval 0.24-0.52; n=4). For prevention of COVID-19, 23 provinces in China issued CM programs. The main principles of CM use were to tonify qi to protect from external pathogens, disperse wind and discharge heat, and resolve dampness. The most frequently used herbs included Radix astragali (Huangqi), Radix glycyrrhizae (Gancao), Radix saposhnikoviae (Fangfeng), Rhizoma Atractylodis Macrocephalae (Baizhu), Lonicerae Japonicae Flos (Jinyinhua), and Fructus forsythia (Lianqiao). CONCLUSIONS: Based on historical records and human evidence of SARS and H1N1 influenza prevention, Chinese herbal formula could be an alternative approach for prevention of COVID-19 in high-risk population. Prospective, rigorous population studies are warranted to confirm the potential preventive effect of CM.",2020,"Luo, Hui; Tang, Qiao-Ling; Shang, Ya-Xi; Liang, Shi-Bing; Yang, Ming; Robinson, Nicola; Liu, Jian-Ping",Chin J Integr Med,3006394629,#1125,
,CZI,Prevention and consideration for the biosafety of laboratory testing under epidemic condition,10.1007/s12072-016-9736-3,,,,"Laboratory testing plays an important role in the diagnosis and treatment of patients with Novel Coronavirus pneumonia. However, the lack of understanding of the virus in the early stage led to great difficulties in biosafety protection for clinical laboratories. Based on the latest researches and findings about the virus, this paper provides some personal opinions on the biosafety prevention in clinical laboratorians under epidemic condition for the reference of laboratory workers.",2020,"YE, Qing; LI, Wei; ZHOU, Mingming; FU, Junfen; SHU, Qiang; GONG, Fangqi; SHANG, Shiqiang",Chinese Journal of Laboratory Medicine,2402472675,#2083,
,CZI,Clinical Features and Treatment of 2019-nCov Pneumonia Patients in Wuhan: Report of A Couple Cases,10.1007/s12250-020-00203-8,,,,"The two patients were a couple. The male was 38 years old, and was admitted to the hospital due to fever for one week and dyspnea for one day on Dec. 27, 2019. On admission, he had slight cough of a little green viscous sputum. He had been treated with normal anti-infective therapy in another hospital for 3 days, but did not respond it. After then, he visited our department. The radiography of the chest at the OPD suggested the right lung infection.ER -",2020,"Zhang, Zhan; Li, Xiaochen; Zhang, Wei; Shi, Zheng-Li; Zheng, Zhishui; Wang, Tao",Virologica Sinica,3004978148,#484,
,CZI,Old Weapon for New Enemy: Drug Repurposing for Treatment of Newly Emerging Viral Diseases,10.1007/s12250-020-00204-7,,,,"In a very recent work by a research team led by Drs. Gengfu Xiao, Wu Zhong and Zhihong Hu, the antiviral efficiency of the FDA-approved drugs including ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine (CQ) and two well-known broad-spectrum antiviral drugs remdesivir (RDV, GS-5734) and favipiravir (T-705) were evaluated against a clinical isolate of 2019-nCoV in a cell culture infection model (Wang et al.2020). The authors found that two compounds CQ (EC50 value?=?1.13 µmol/L; CC50?>?100 µmol/L, SI?>?88.50) and RDV (EC50?=?0.77 µmol/L; CC50?>?100 µmol/L; SI?>?129.87) potently blocked virus infection at low-micromolar concentration and showed high selectivity index (SI). From the in vitro results, these two compounds appear promising to be transformed into clinical drugs for treatment of 2019-nCoV infections.AU - Guo, Deyin",2020,,Virologica Sinica,3006339206,#651,
,CZI,Compensation of ACE2 Function for Possible Clinical Management of 2019-nCoV-Induced Acute Lung Injury,10.1007/s12250-020-00205-6,,32034638,,,2020,"Wu, Yuntao",Virol Sin,3004883038,#485,
,CZI,The First Disease X is Caused by a Highly Transmissible Acute Respiratory Syndrome Coronavirus,10.1007/s12250-020-00206-5,,,,"Based on the announcement of the World Health Organization (WHO) in 2018, the Wuhan pneumonia caused by an unknown etiology should be recognized as the first Disease X. Later, the pathogen was identified to be a novel coronavirus denoted 2019-nCoV, which has 79.5% and 96% whole genome sequence identify to SARS-CoV and bat SARS-related coronavirus (SARSr-CoV-RaTG13), respectively, suggesting its potential bat origin. With high human-to-human transmission rate (R0), 2019-nCoV has quickly spread in China and other countries, resulting in 34,953 confirmed cases and 725 deaths as of 8 February 2020, thus calling for urgent development of therapeutics and prophylactics. Here we suggest renaming 2019-nCoV as “transmissible acute respiratory syndrome coronavirus (TARS-CoV)” and briefly review the advancement of research and development of neutralizing antibodies and vaccines targeting the receptor-binding domain (RBD) and viral fusion inhibitors targeting the heptad repeat 1 (HR1) domain in spike protein of 2019-nCoV.",2020,"Jiang, Shibo; Shi, Zheng-Li",Virologica Sinica,3006422522,#969,
,CZI,Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools,10.1007/s12250-020-00207-4,,32125642,,"Currently there is no effective antiviral therapy for SARS-CoV-2 infection, which frequently leads to fatal inflammatory responses and acute lung injury. Here, we discuss the various mechanisms of SARS-CoV-mediated inflammation. We also assume that SARS-CoV-2 likely shares similar inflammatory responses. Potential therapeutic tools to reduce SARS-CoV-2-induced inflammatory responses include various methods to block FcR activation. In the absence of a proven clinical FcR blocker, the use of intravenous immunoglobulin to block FcR activation may be a viable option for the urgent treatment of pulmonary inflammation to prevent severe lung injury. Such treatment may also be combined with systemic anti-inflammatory drugs or corticosteroids. However, these strategies, as proposed here, remain to be clinically tested for effectiveness.",2020,"Fu, Yajing; Cheng, Yuanxiong; Wu, Yuntao",Virol Sin,3006390878,#3407,
,CZI,The Risk and Prevention of Novel Coronavirus Pneumonia Infections Among Inpatients in Psychiatric Hospitals,10.1007/s12264-020-00476-9,,,,"Since the middle of December 2019, human-to-human transmission of novel coronavirus pneumonia (NCP, also called COVID-19) has occurred among close contacts [1]. After the outbreak on January 21, 2020, it was swiftly included among the Class B infectious diseases stipulated in the Law of the People’s Republic of China on the Prevention and Control of Infectious Diseases, and measures for prevention and control of Class A infectious diseases were adopted. At 21:27 on February 12, 2020, the China News Network updated information to include epidemic data from the National Health Commission and official channels in Hong Kong, Macao, and Taiwan regions: the highest death rate was in Wuhan City (Table 1). Overload of inpatients at hospitals may play a negative role in the overall therapeutic effect and contribute to the death rateER -",2020,"Zhu, Yuncheng; Chen, Liangliang; Ji, Haifeng; Xi, Maomao; Fang, Yiru; Li, Yi",Neuroscience Bulletin,2006683952,#1720,
,CZI,A numerical study of ventilation strategies for infection risk mitigation in general inpatient wards,10.1007/s12273-020-0623-4,,,,"Aerial dispersion of human exhaled microbial contaminants and subsequent contamination of surfaces is a potential route for infection transmission in hospitals. Most general hospital wards have ventilation systems that drive air and thus contaminants from the patient areas towards the corridors. This study investigates the transport mechanism and deposition patterns of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) within a typical six bedded general inpatient ward cubicle through numerical simulation. It demonstrates that both air change and exhaust airflow rates have significant effects on not only the airflow but also the particle distribution within a mechanically ventilated space. Moreover, the location of an infected patient within the ward cubicle is crucial in determining the extent of infection risk to other ward occupants. Hence, it is recommended to provide exhaust grilles in close proximity to a patient, preferably above each patient’s bed. To achieve infection prevention and control, high exhaust airflow rate is also suggested. Regardless of the ventilation design, all patients and any surfaces within a ward cubicle should be regularly and thoroughly cleaned and disinfected to remove microbial contamination. The outcome of this study can serve as a source of reference for hospital management to better ventilation design strategies for mitigating the risk of infection.",2020,"Satheesan, Manoj Kumar; Mui, Kwok Wai; Wong, Ling Tim",Building Simulation,2886620552,#1937,
,CZI,"Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts' consensus statement",10.1007/s12519-020-00343-7,,32034659,,"Since the outbreak of 2019 novel coronavirus infection (2019-nCoV) in Wuhan City, China, by January 30, 2020, a total of 9692 confirmed cases and 15,238 suspected cases have been reported around 31 provinces or cities in China. Among the confirmed cases, 1527 were severe cases, 171 had recovered and been discharged at home, and 213 died. And among these cases, a total of 28 children aged from 1 month to 17 years have been reported in China. For standardizing prevention and management of 2019-nCoV infections in children, we called up an experts' committee to formulate this experts' consensus statement. This statement is based on the Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (the fourth edition) (National Health Committee) and other previous diagnosis and treatment strategies for pediatric virus infections. The present consensus statement summarizes current strategies on diagnosis, treatment, and prevention of 2019-nCoV infection in children.",2020,"Shen, Kunling; Yang, Yonghong; Wang, Tianyou; Zhao, Dongchi; Jiang, Yi; Jin, Runming; Zheng, Yuejie; Xu, Baoping; Xie, Zhengde; Lin, Likai; Shang, Yunxiao; Lu, Xiaoxia; Shu, Sainan; Bai, Yan; Deng, Jikui; Lu, Min; Ye, Leping; Wang, Xuefeng; Wang, Yongyan; Gao, Liwei; China National Clinical Research Center for Respiratory, Diseases; National Center for Children’s Health, Beijing China; Group of Respirology, Chinese Pediatric Society Chinese Medical Association; Chinese Medical Doctor Association Committee on Respirology, Pediatrics; China Medicine Education Association Committee on, Pediatrics; Chinese Research Hospital Association Committee on, Pediatrics; Chinese Non-government Medical Institutions Association Committee on, Pediatrics; China Association of Traditional Chinese Medicine, Committee on Children’s Health; Medicine, Research; China News of Drug Information Association, Committee on Children’s Safety Medication; Global Pediatric Pulmonology, Alliance",World J Pediatr,3004896587,#482,
,CZI,Recommendation for the diagnosis and treatment of novel coronavirus infection in children in Hubei (Trial version 1),10.1007/s12519-020-00343-7,,32051073,,"Since December 2019, a cluster of patients have been diagnosed to be infected with 2019 novel coronavirus (2019-nCoV) in Wuhan, China. The epidemic has been spreading to other areas of the country and abroad. A few cases have progressed rapidly to acute respiratory distress syndrome and/or multiple organ function failure. The epidemiological survey has indicated that the general population is susceptible to 2019-nCoV. A total of 14 children (6 months to 14 years of age, including 5 cases in Wuhan) have been confirmed to be infected with 2019-nCoV in China so far. In order to further standardize and enhance the clinical management of 2019-nCoV infection in children, reduce the incidence, and decrease the number of severe cases, we have formulated this diagnosis and treatment recommendation according to the recent information at home and abroad.",2020,"Pediatric Branch of Hubei Medical, Association; Pediatric Branch of Wuhan Medical, Association; Pediatric Medical Quality Control Center of, Hubei",Zhongguo Dang Dai Er Ke Za Zhi,3004896587,#813,
,CZI,Diagnosis and treatment of 2019 novel coronavirus infection in children: a pressing issue,10.1007/s12519-020-00344-6,,,,"Clinical features of infected pediatric patients The age of onset ranged from 1 month to 17 years in the 28 confirmed pediatric patients. All were family clusters or with a close contact history. The clinical features are variable in pediatric patients. Several patients displayed no obvious clinical symptoms at diagnosis, and they were found by screening because of close contacts with confirmed patients; and further chest imaging suggested pneumonia. Several gradually presented with fever, fatigue, dry cough, accompanied by other upper respiratory symptoms including nasal congestion, runny nose, and seldom gastrointestinal symptoms such as nausea, vomiting and diarrhea. Laboratory examination in pediatric patients showed that blood routine was often normal, and C-reactive protein was normal or transiently elevated. Lung imaging examination revealed mild increase of lung markings or ground-glass opacity or pneumoniaID - Shen2020",2020,"Shen, Kun-Ling; Yang, Yong-Hong",World Journal of Pediatrics,3004943457,#276,
,CZI,Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus,10.1007/s12519-020-00345-5,,,,"Since December 2019, an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China. As of 8 pm, 31 January 2020, more than 20 pediatric cases have been reported in China. Of these cases, ten patients were identified in Zhejiang Province, with an age of onset ranging from 112 days to 17 years. Following the latest National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCoV (the 4th edition) and current status of clinical practice in Zhejiang Province, recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health, the National Children’s Regional Medical Center, Children’s Hospital, Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.",2020,"Chen, Zhi-Min; Fu, Jun-Fen; Shu, Qiang; Chen, Ying-Hu; Hua, Chun-Zhen; Li, Fu-Bang; Lin, Ru; Tang, Lan-Fang; Wang, Tian-Lin; Wang, Wei; Wang, Ying-Shuo; Xu, Wei-Ze; Yang, Zi-Hao; Ye, Sheng; Yuan, Tian-Ming; Zhang, Chen-Mei; Zhang, Yuan-Yuan",World Journal of Pediatrics,3005489812,#334,
,CZI,New coronavirus: new challenges for pediatricians,10.1007/s12519-020-00346-4,,,,"Children comprise a special population whose immune response system is distinct from adults. Therefore, pediatric patients infected with 2019-nCoV have their own clinical features and therapeutic responses. Herein, we formulate this recommendation for diagnosis and treatment of 2019-nCoV infection in children which is of paramount importance for clinical practiceSN - 1867-0687",2020,"Chen, Zhi-Min; Fu, Jun-Fen; Shu, Qiang",World Journal of Pediatrics,3005938935,#572,
,CZI,Management strategies of neonatal jaundice during the coronavirus disease 2019 outbreak,10.1007/s12519-020-00347-3,,32112336,,"The outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV) has become a most challenging health emergency. Owing to rigorous quarantine and control measures taken in China, routine neonatal health surveillance and follow-up have become challenging. Without follow-up surveillance, some rapid and progressive newborn diseases, such as bilirubin encephalopathy, may be ignored. The characteristics of onset age of kernicterus suggest that monitoring of bilirubin level at home provides a useful way to alert hospital visits and to prevent the development of extremely hyperbilirubinemia. Therefore, we developed an online follow-up program for convenient monitoring of bilirubin level of newborns that is based on our practical experiences. The aim is to make our management strategies of neonatal jaundice tailored to the infection prevention and control during the COVID-19 epidemic.",2020,"Ma, X. L.; Chen, Z.; Zhu, J. J.; Shen, X. X.; Wu, M. Y.; Shi, L. P.; Du, L. Z.; Fu, J. F.; Shu, Q.",World journal of pediatrics : WJP,3004657851,#2898,
,CZI,Practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-nCoV) patients,10.1007/s12630-020-01591-x,,32052373,,"A global health emergency has been declared by the World Health Organization as the 2019-nCoV outbreak spreads across the world, with confirmed patients in Canada. Patients infected with 2019-nCoV are at risk for developing respiratory failure and requiring admission to critical care units. While providing optimal treatment for these patients, careful execution of infection control measures is necessary to prevent nosocomial transmission to other patients and to healthcare workers providing care. Although the exact mechanisms of transmission are currently unclear, human-to-human transmission can occur, and the risk of airborne spread during aerosol-generating medical procedures remains a concern in specific circumstances. This paper summarizes important considerations regarding patient screening, environmental controls, personal protective equipment, resuscitation measures (including intubation), and critical care unit operations planning as we prepare for the possibility of new imported cases or local outbreaks of 2019-nCoV. Although understanding of the 2019-nCoV virus is evolving, lessons learned from prior infectious disease challenges such as Severe Acute Respiratory Syndrome will hopefully improve our state of readiness regardless of the number of cases we eventually manage in Canada.",2020,"Wax, Randy S.; Christian, Michael D.",Can J Anaesth,3005561939,#874,
,CZI,What we do when a COVID-19 patient needs an operation: operating room preparation and guidance,10.1007/s12630-020-01617-4,,,,"We read with interest the recent review in the Journal by Wax and Christian1 on coronavirus disease 2019 (COVID-19). The first case of COVID-19 in Singapore was confirmed on 23 January 2020.2 In the week of February 13–19, the World Health Organization reported that Singapore had more cases of COVID-19 than any other country outside of mainland China.3 We wish to share the protocol that we use in our hospital in preparing an operating room (OR) for confirmed or suspected COVID-19 patients coming for surgery. An OR with a negative pressure environment located at a corner of the operating complex, and with a separate access, is designated for all confirmed (or suspected) COVID-19 cases. The OR actually consists of five interconnected rooms, of which only the ante room and anesthesia induction rooms have negative atmospheric pressures. The OR proper, preparation, and scrub rooms all have positive pressures (eFig. 1 in the Electronic Supplementary Material [ESM]). Understanding the airflow within the OR is crucial to minimizing the risk of infection. The same OR and the same anesthesia machine will only be used for COVID-19 cases for the duration of the epidemic. An additional heat and moisture exchanger (HME) filter is placed on the expiratory limb of the circuit. Both HME filters and the soda lime are changed after each case. The anesthetic drug trolley is kept in the induction room. Before the start of each operation, the anesthesiologist puts all the drugs and equipment required for the procedure onto a tray to avoid handling of the drug trolley during the case. Nevertheless, if there is a need for additional drugs, hand hygiene and glove changing are performed before entering the induction room and handling the drug trolley.SN - 1496-8975",2020,"Ti, Lian Kah; Ang, Lin Stella; Foong, Theng Wai; Ng, Bryan Su Wei",Canadian Journal of Anesthesia/Journal canadien d'anesthésie,2147204280,#5491,
,CZI,"Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV)",10.1007/s13337-020-00571-5,,,,"The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV.",2020,"Kumar, Swatantra; Maurya, Vimal K.; Prasad, Anil K.; Bhatt, Madan L. B.; Saxena, Shailendra K.",VirusDisease,3006282354,#4531,
,CZI,Coronavirus: Stehen wir am Beginn einer neuen Pandemie?,10.1007/s15006-020-0080-0,,,,"Beunruhigende Nachrichten aus China, erste Erkrankungsfälle in Europa. Das Coronoavirus breitet sich aus. MMW-Schriftleiter Prof. Johannes Bogner, München, berichtet aus infektiologischer Sicht über den derzeitigen Kenntnisstand und macht Sie zugleich fit für Fragen Ihrer Patienten.",2020,"Bogner, Johannes R.",MMW - Fortschritte der Medizin,3005035093,#144,
,CZI,2019 Novel coronavirus: where we are and what we know,10.1007/s15010-020-01401-y,,,,"There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.",2020,"Cheng, Zhangkai J.; Shan, Jing",Infection,3004114601,#1221,
,CZI,"Coronavirus outbreaks: prevention and management recommendationsAB - What role can pharmacists play? The International Pharmaceutical Federation is emphasizing the active role of community and hospital pharmacists can play in preventing the spread of COVID-19 [17]. Pharmacists are often a reliable and first point of contact for individuals having concerns or needing information and advice regarding ailments. Moreover, pharmacists are readily available at community pharmacies and hospital and accessible to the general population. Essential responsibilities of pharmacists include: having appropriate medicinal products in stock; promoting proper handwashing to prevent disease; controlling in-hospital infection; and providing patient care and support. Pharmacists also play a crucial role in the prevention, early detection of certain types of new cases and referring suspected cases to the relevant healthcare authorities [17].JO - Drugs & Therapy Perspectives",10.1007/s40267-020-00717-x,,,,,2020,"Khan, Zakir; Muhammad, Khayal; Ahmed, Ali; Rahman, Hazir",,2293363732,#4768,
,CZI,The SARS-CoV-2 Vaccine Pipeline: an Overview,10.1007/s40475-020-00201-6,,,,"The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease (COVID-19).",2020,"Chen, Wen-Hsiang; Strych, Ulrich; Hotez, Peter J.; Bottazzi, Maria Elena",Current Tropical Medicine Reports,2609522093,#3200,
,CZI,COVID-19: a critical care perspective informed by lessons learnt from other viral epidemics,10.1016/j.accpm.2020.02.002,,,,,2020,"Ling, Lowell; Joynt, Gavin M.; Lipman, Jeff; Constantin, Jean-Michel; Joannes-Boyau, Olivier",Anaesthesia Critical Care & Pain Medicine,2153224243,#1382,
,CZI,Coronavirus Disease 2019 (COVID-19): A critical care perspective beyond China,10.1016/j.accpm.2020.03.001,,,,,2020,"Rello, Jordi; Tejada, Sofia; Userovici, Caroline; Arvaniti, Kostoula; Pugin, Jérôme; Waterer, Grant",Anaesthesia Critical Care & Pain Medicine,2604381070,#4462,
,CZI,Corona Virus International Public Health Emergencies: Implications for Radiology Management,10.1016/j.acra.2020.02.003,,,,"The outbreak of 2019 novel coronavirus (2019-nCoV) pneumonia was reported in Wuhan, Hubei Province, China in December 2019 and has spread internationally. This article discusses how radiology departments can most effectively respond to this public health emergency.",2020,"Zhang, Han-Wen; Yu, Juan; Xu, Hua-Jian; Lei, Yi; Pu, Zu-Hui; Dai, Wei-Cai; Lin, Fan; Wang, Yu-Li; Wu, Xiao-Liu; Liu, Li-Hong; Li, Min; Mo, Yong-Qian; Zhang, Hong; Luo, Si-Ping; Chen, Huan; Lyu, Gui-Wen; Zhou, Zhao-Guang; Liu, Wei-Min; Liu, Xiao-Lei; Song, Hai-Yan; Chen, Fu-Zhen; Zeng, Liang; Zhong, Hua; Guo, Ting-Ting; Hu, Ya-Qiong; Yang, Xin-Xin; Liu, Pin-Ni; Li, Ding-Fu",Academic Radiology,2380955547,#2064,
,CZI,"A climatologic investigation of the SARS-CoV outbreak in Beijing, China",10.1016/j.ajic.2005.12.006,,,,"The first cases of severe acute respiratory syndrome (SARS) were identified in November 2002, in Guangdong Province, China. The epidemic spread rapidly within China and internationally, with 8454 recorded infections and 792 deaths by June 15, 2003. Temperature, relative humidity, and wind velocity were the three key meteorological determinants affecting the transmission of SARS. The peak spread of SARS occurred at a mean temperature of 16.9 degrees C (95% CI, 10.7 degrees C to 23.1 degrees C), with a mean relative humidity of 52.2% (95% CI, 33.0% to 71.4%) and wind speed of 2.8 ms(-1) (95% CI, 2.0 to 3.6 ms(-1)). In northern China, these conditions are most likely to occur in the spring and suggest that SARS has a seasonal nature akin to viruses such as influenza and the common cold. A regression equation (Y=218.692-0.698X(t)-2.043X(h)+2.282X(w)) was derived to represent the optimal climatic conditions for the 2003 SARS epidemic. Further investigations in other regions are necessary to verify these results.",2006,"Yuan, J.; Yun, H.; Lan, W.; Wang, W.; Sullivan, S. G.; Jia, S.; Bittles, A. H.",American Journal of Infection Control,1963995582,#2072,
,CZI,A systematic risk-based strategy to select personal protective equipment for infectious diseases,10.1016/j.ajic.2019.06.023,,,,"Background: Personal protective equipment (PPE) is a primary strategy to protect health care personnel (HCP) from infectious diseases. When transmission-based PPE ensembles are not appropriate, HCP must recognize the transmission pathway of the disease and anticipate the exposures to select PPE. Because guidance for this process is extremely limited, we proposed a systematic, risk-based approach to the selection and evaluation of PPE ensembles to protect HCP against infectious diseases. Methods: The approach used in this study included the following 4 steps: (1) job hazard analysis, (2) infectious disease hazard analysis, (3) selection of PPE, and (4) evaluation of selected PPE. Selected PPE should protect HCP from exposure, be usable by HCP, and fit for purpose. Results: The approach was demonstrated for the activity of intubation of a patient with methicillin-resistant Staphylococcus aureus or Severe Acute Respiratory Syndrome coronavirus. As expected, the approach led to the selection of different ensembles of PPE for these 2 pathogens. Discussion: A systematic risk-based approach to the selection of PPE will help health care facilities and HCP select PPE when transmission-based precautions are not appropriate. Owing to the complexity of PPE ensemble selection and evaluation, a team with expertise in infectious diseases, occupational health, the health care activity, and related disciplines, such as human factors, should be engaged. Conclusions: Participation, documentation, and transparency are necessary to ensure the decisions can be communicated, critiqued, and understood by HCP. (C) 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.",2020,"Jones, Rachael M.; Bleasdale, Susan C.; Maita, Dayana; Brosseau, Lisa M.; Program, C. D. C. Prevention Epictr",American Journal of Infection Control,2964662575,#3682,
,CZI,Coronavirus Disease 2019 (COVID-19) and Pregnancy: What obstetricians need to know,10.1016/j.ajog.2020.02.017,,,,"Coronavirus Disease 2019 (COVID-19) is an emerging disease with a rapid increase in cases and deaths since its first identification in Wuhan, China, in December 2019. Limited data are available about COVID-19 during pregnancy; however, information on illnesses associated with other highly pathogenic coronaviruses (i.e., severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS)) might provide insights into COVID-19’s effects during pregnancy.",2020,"Rasmussen, Sonja A.; Smulian, John C.; Lednicky, John A.; Wen, Tony S.; Jamieson, Denise J.",American Journal of Obstetrics and Gynecology,2604381070,#1778,
,CZI,Fear of COVID 2019: First suicidal case in India !,10.1016/j.ajp.2020.101989,,,,,2020,"Goyal, Kapil; Chauhan, Poonam; Chhikara, Komal; Gupta, Parakriti; Singh, Mini P.",Asian Journal of Psychiatry,1995569061,#2278,
,CZI,Iranian mental health during the COVID-19 epidemic,10.1016/j.ajp.2020.101990,,,,,2020,"Zandifar, Atefeh; Badrfam, Rahim",Asian Journal of Psychiatry,2959884400,#4381,
,CZI,SARS-CoV-2: a novel deadly virus in a globalised world,10.1016/j.antiviral.2005.10.005,,32078595,,,2020,"Dilcher, Meik; Werno, Anja; Jennings, Lance C.",N Z Med J,2047323912,#1662,
,CZI,Comparison of broad-spectrum antiviral activities of the synthetic rocaglate CR-31-B (−) and the eIF4A-inhibitor Silvestrol,10.1016/j.antiviral.2020.104706,,,,"Rocaglates, a class of natural compounds isolated from plants of the genus Aglaia, are potent inhibitors of translation initiation. They are proposed to form stacking interactions with polypurine sequences in the 5′-untranslated region (UTR) of selected mRNAs, thereby clamping the RNA substrate onto eIF4A and causing inhibition of the translation initiation complex. Since virus replication relies on the host translation machinery, it is not surprising that the rocaglate Silvestrol has broad-spectrum antiviral activity. Unfortunately, synthesis of Silvestrol is sophisticated and time-consuming, thus hampering the prospects for further antiviral drug development. Here, we present the less complex structured synthetic rocaglate CR-31-B (−) as a novel compound with potent broad-spectrum antiviral activity in primary cells and in an ex vivo bronchial epithelial cell system. CR-31-B (−) inhibited the replication of corona-, Zika-, Lassa-, Crimean Congo hemorrhagic fever viruses and, to a lesser extent, hepatitis E virus (HEV) at non-cytotoxic low nanomolar concentrations. Since HEV has a polypurine-free 5′-UTR that folds into a stable hairpin structure, we hypothesized that RNA clamping by Silvestrol and its derivatives may also occur in a polypurine-independent but structure-dependent manner. Interestingly, the HEV 5′-UTR conferred sensitivity towards Silvestrol but not to CR-31-B (−). However, if an exposed polypurine stretch was introduced into the HEV 5′-UTR, CR-31-B (−) became an active inhibitor comparable to Silvestrol. Moreover, thermodynamic destabilization of the HEV 5′-UTR led to reduced translational inhibition by Silvestrol, suggesting differences between rocaglates in their mode of action, most probably by engaging Silvestrol's additional dioxane moiety.",2020,"Müller, Christin; Obermann, Wiebke; Schulte, Falk W.; Lange-Grünweller, Kerstin; Oestereich, Lisa; Elgner, Fabian; Glitscher, Mirco; Hildt, Eberhard; Singh, Kamini; Wendel, Hans-Guido; Hartmann, Roland K.; Ziebuhr, John; Grünweller, Arnold",Antiviral Research,,#2162,
,CZI,The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade,10.1016/j.antiviral.2020.104742,,,,"In 2019, a new coronavirus (2019-nCoV) infecting Humans has emerged in Wuhan, China. Its genome has been sequenced and the genomic information promptly released. Despite a high similarity with the genome sequence of SARS-CoV and SARS-like CoVs, we identified a peculiar furin-like cleavage site in the Spike protein of the 2019-nCoV, lacking in the other SARS-like CoVs. In this article, we discuss the possible functional consequences of this cleavage site in the viral cycle, pathogenicity and its potential implication in the development of antivirals.",2020,"Coutard, B.; Valle, C.; de Lamballerie, X.; Canard, B.; Seidah, N. G.; Decroly, E.",Antiviral Research,3005409321,#624,
,CZI,Of chloroquine and COVID-19,10.1016/j.antiviral.2020.104762,,,,"Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2). The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research.",2020,"Touret, Franck; de Lamballerie, Xavier",Antiviral Research,3006304371,#4426,
,CZI,Recent advances in lab-on-a-chip technologies for viral diagnosis,10.1016/j.bios.2020.112041,,,,"The global risk of viral disease outbreaks emphasizes the need for rapid, accurate, and sensitive detection techniques to speed up diagnostics allowing early intervention. An emerging field of microfluidics also known as the lab-on-a-chip (LOC) or micro total analysis system includes a wide range of diagnostic devices. This review briefly covers both conventional and microfluidics-based techniques for rapid viral detection. We first describe conventional detection methods such as cell culturing, immunofluorescence or enzyme-linked immunosorbent assay (ELISA), or reverse transcription polymerase chain reaction (RT-PCR). These methods often have limited speed, sensitivity, or specificity and are performed with typically bulky equipment. Here, we discuss some of the LOC technologies that can overcome these demerits, highlighting the latest advances in LOC devices for viral disease diagnosis. We also discuss the fabrication of LOC systems to produce devices for performing either individual steps or virus detection in samples with the sample to answer method. The complete system consists of sample preparation, and ELISA and RT-PCR for viral-antibody and nucleic acid detection, respectively. Finally, we formulate our opinions on these areas for the future development of LOC systems for viral diagnostics.",2020,"Zhu, Hanliang; Fohlerová, Zdenka; Pekárek, Jan; Basova, Evgenia; Neužil, Pavel",Biosensors and Bioelectronics,3002683399,#156,
,CZI,Outbreak of a new coronavirus: what anaesthetists should know,10.1016/j.bja.2020.02.008,,32115186,,,2020,"Peng, Philip W. H.; Ho, Pak-Leung; Hota, Susy S.",British journal of anaesthesia,2044189336,#3894,
,CZI,Laboratory biosafety guide for the novel coronavirus,10.1016/j.bsheal.2020.01.001,,,,,2020,"Department of Health Science, Technology; Education, National Health Commission of People's Republic of China",Biosafety and Health,2619475730,#119,
,CZI,Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis,10.1016/j.cca.2020.03.004,,,,,2020,"Lippi, Giuseppe; Plebani, Mario",Clinica Chimica Acta,3006645647,#4506,
,CZI,"Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to Feb 2020",10.1016/j.cca.2020.03.009,,,,"Background There’s an outbreak of a novel coronavirus (SARS-CoV-2) infection since December 2019, first in China, and currently with more than 80 thousand confirmed infection globally in 29 countries till March 2, 2020. Identification, isolation and caring for patients early are essential to limit human-to-human transmission including reducing secondary infections among close contacts and health care workers, preventing transmission amplification events. The RT-PCR detection of viral nucleic acid test (NAT) was one of the most quickly established laboratory diagnosis method in a novel viral pandemic, just as in this COVID-19 outbreak. Methods 4880 cases that had respiratory infection symptoms or close contact with COVID-19 patients in hospital in Wuhan, China, were tested for SARS-CoV-2 infection by use of quantitative RT-PCR (qRT-PCR) on samples from the respiratory tract. Positive rates were calculated in groups divided by genders or ages. Results The positive rate was about 38% for the total 4880 specimens. Male and older population had a significant higher positive rates. However, 57% was positive among the specimens from the Fever Clinics. Binary logistic regression analysis showed that age, not gender, was the risk factor for SARS-CoV-2 infection in fever clinics. Conclusions Therefore, we concluded that viral NAT played an important role in identifying SARS-CoV-2 infection.",2020,"Liu, Rui; Han, Huan; Liu, Fang; Lv, Zhihua; Wu, Kailang; Liu, Yingle; Feng, Yong; Zhu, Chengliang",Clinica Chimica Acta,2053972970,#5447,
,CZI,The Novel Coronavirus Outbreak: What We Know and What We Don’t,10.1016/j.cell.2020.02.027,,,,"Phylogenetic analyses reveal that SARS-CoV-2 is closely related to a group of SARS-like coronaviruses. However, it remains unclear where the virus comes from and how it was transmitted to humans in the first place. Unlike with other zoonotic agents such as hantavirus and arenavirus, thus far we haven’t found a SARS virus in animals that is the same as that in humans. Fortunately, SARS virus has not appeared in humans since 2004. In contrast, this new virus seems to have stronger transmission capabilities among people. Compared to the primary virus in humans, we still know less about whether, what, and how the virus has changed and the effect of the changes for their epidemics in humans. Control and prevention of the disease is especially difficult in China and elsewhere if there are infected individuals with no clinical signs.",2020,,Cell,2405540444,#1886,
,CZI,SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor,10.1016/j.cell.2020.02.052,,,,"The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.",,"Hoffmann, Markus; Kleine-Weber, Hannah; Schroeder, Simon; Krüger, Nadine; Herrler, Tanja; Erichsen, Sandra; Schiergens, Tobias S.; Herrler, Georg; Wu, Nai-Huei; Nitsche, Andreas; Müller, Marcel A.; Drosten, Christian; Pöhlmann, Stefan",Cell,3006448444,#4561,
,CZI,A novel coronavirus (COVID-19) outbreak: a call for action,10.1016/j.chest.2020.02.014,,,,,2020,"Zhang, Yi; Xu, Jiuyang; Li, Hui; Cao, Bin",Chest,3005943294,#1256,
,CZI,Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China,10.1016/j.chom.2020.02.001,,,,"An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.",2020,"Wu, Aiping; Peng, Yousong; Huang, Baoying; Ding, Xiao; Wang, Xianyue; Niu, Peihua; Meng, Jing; Zhu, Zhaozhong; Zhang, Zheng; Wang, Jiangyuan; Sheng, Jie; Quan, Lijun; Xia, Zanxian; Tan, Wenjie; Cheng, Genhong; Jiang, Taijiao",Cell Host & Microbe,3004896487,#546,
,CZI,Asymptomatic novel coronavirus pneumonia patient outside WuHan: The value of CT images in the course of the disease,10.1016/j.clinimag.2020.02.008,,,,"The purpose of this case report is to describe the imaging and associated clinical features of an asymptomatic novel coronavirus pneumonia (COVID-19) patient outside WuHan, China. The principle findings are that in this patient with laboratory-confirmed COVID-19, CT findings preceded symptoms and included bilateral pleural effusions, previously not reported in association with COVID-19. The role of this case report is promotion of potential recognition amongst radiologists of this new disease, which has been declared a global health emergency by the World Health Organization (WHO).",2020,"Lin, Chen; Ding, Yuxiao; Xie, Bin; Sun, Zhujian; Li, Xiaogang; Chen, Zixian; Niu, Meng",Clinical Imaging,3004511262,#1575,
,CZI,Novel coronavirus: how things are in Wuhan,10.1016/j.cmi.2020.02.005,,,,,2020,"Khan, S.; Nabi, G.; Han, G.; Siddique, R.; Lian, S.; Shi, H.; Bashir, N.; Ali, A.; Shereen, M. A.",Clinical Microbiology and Infection,3006085809,#3378,
,CZI,"First Atypical case of 2019 novel coronavirus in Yan'an, China",10.1016/j.cmi.2020.02.011,,,,,2020,"Hao, Wendong; Li, Manxiang; Huang, Xiaoqi",Clinical Microbiology and Infection,3004790666,#1303,
,CZI,"Computers and viral diseases. Preliminary bioinformatics studies on the design of a synthetic vaccine and a preventative peptidomimetic antagonist against the SARS-CoV-2 (2019-nCoV, COVID-19) coronavirus",10.1016/j.compbiomed.2020.103670,,,,"This paper concerns study of the genome of the Wuhan Seafood Market isolate believed to represent the causative agent of the disease COVID-19. This is to find a short section or sections of viral protein sequence suitable for preliminary design proposal for a peptide synthetic vaccine and a peptidomimetic therapeutic, and to explore some design possibilities. The project was originally directed towards a use case for the Q-UEL language and its implementation in a knowledge management and automated inference system for medicine called the BioIngine, but focus here remains mostly on the virus itself. However, using Q-UEL systems to access relevant and emerging literature, and to interact with standard publically available bioinformatics tools on the Internet, did help quickly identify sequences of amino acids that are well conserved across many coronaviruses including 2019-nCoV. KRSFIEDLLFNKV was found to be particularly well conserved in this study and corresponds to the region around one of the known cleavage sites of the SARS virus that are believed to be required for virus activation for cell entry. This sequence motif and surrounding variations formed the basis for proposing a specific synthetic vaccine epitope and peptidomimetic agent. The work can, nonetheless, be described in traditional bioinformatics terms, and readily reproduced by others, albeit with the caveat that new data and research into 2019-nCoV is emerging and evolving at an explosive pace. Preliminary studies using molecular modeling and docking, and in that context the potential value of certain known herbal extracts, are also described.",2020,"Robson, B.",Computers in Biology and Medicine,1655564745,#1938,
,CZI,"History is repeating itself, a probable zoonotic spillover as a cause of an epidemic: the case of 2019 novel Coronavirus",10.1016/j.cortex.2016.02.016,,32009128,,"Pathogen transmission from a vertebrate animal to a human, also known as zoonotic spillover, represents a global public health burden, which while associated with multiple outbreaks, still remains a poorly understood phenomenon. Coronaviruses, like influenza viruses, circulate in nature in various animal species. Alpha-coronaviruses and beta-coronaviruses can infect mammals and gamma-coronaviruses and delta-coronaviruses tend to infect birds, but some of them can also be transmitted to mammals. Although still preliminary, current data suggest that bats are the most probable initial source of the current 2019 novel CoV (2019nCoV) outbreak, that begun on December 2019 in Wuhan, China, apparently spreading from a ""wet market"" to multiple cities and provinces in China. This epidemic of 2019nCoV, already reaching more than 6,000 cases to-day (end of January 2020) (>90% in China), will not be the last one linked to zoonotic spillover events.",2020,"Rodriguez-Morales, Alfonso J.; Bonilla-Aldana, D. Katterine; Balbin-Ramon, Graciela Josefina; Rabaan, Ali A.; Sah, Ranjit; Paniz-Mondolfi, Alberto; Pagliano, Pasquale; Esposito, Silvano",Infez Med,2297614983,#277,
,CZI,New thinking in the treatment of 2019 novel coronavirus pneumonia,10.1016/j.ctcp.2020.101131,,,,,2020,"Yang, Qing-Xin; Zhao, Ting-Hui; Sun, Chong-Zhou; Wu, Li-Meng; Dai, Qiang; Wang, Shuai-dao; Tian, Hui",Complementary Therapies in Clinical Practice,3004824173,#4388,
,CZI,Effects of progressive muscle relaxation on anxiety and sleep quality in patients with COVID-19,10.1016/j.ctcp.2020.101132,,,,"Background Patients with Coronavirus Disease 2019(COVID-19) will experience high levels of anxiety and low sleep quality due to isolation treatment. Some sleep-improving drugs may inhibit the respiratory system and worsen the condition. Prolonged bedside instruction may increase the risk of medical infections. Objective To investigate the effect of progressive muscle relaxation on anxiety and sleep quality of COVID-19. Methods In this randomized controlled clinical trial, a total of 51 patients who entered the isolation ward were included in the study and randomly divided into experimental and control groups. The experimental group used progressive muscle relaxation (PMR) technology for 30 min per day for 5 consecutive days. During this period, the control group received only routine care and treatment. Before and after the intervention, the Spielberger State-Trait Anxiety Scale (STAI) and Sleep State Self-Rating Scale (SRSS) were used to measure and record patient anxiety and sleep quality. Finally, data analysis was performed using SPSS 25.0 software. Results The average anxiety score (STAI) before intervention was not statistically significant (P = 0.730), and the average anxiety score after intervention was statistically significant (P < 0.001). The average sleep quality score (SRSS) of the two groups before intervention was not statistically significant (P = 0.838), and it was statistically significant after intervention (P < 0.001). Conclusion Progressive muscle relaxation as an auxiliary method can reduce anxiety and improve sleep quality in patients with COVID-19.",2020,"Liu, Kai; Chen, Ying; Wu, Duozhi; Lin, Ruzheng; Wang, Zaisheng; Pan, Liqing",Complementary Therapies in Clinical Practice,2904096912,#4505,
,CZI,Recent discovery and development of inhibitors targeting coronaviruses,10.1016/j.drudis.2020.01.015,,,,"Human coronaviruses (CoVs) are enveloped viruses with a positive-sense single-stranded RNA genome. Currently, six human CoVs have been reported including human coronavirus 229E (HCoV-229E), OC43 (HCoV-OC43), NL63 (HCoV-NL63), HKU1 (HCoV-HKU1), severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and MiddleEast respiratory syndrome (MERS) coronavirus (MERS-CoV). They cause moderate to severe respiratory and intestinal infections in humans. In this review, we focus on recent advances in the research and development of small-molecule anti-human coronavirus therapies targeting different stages of the CoV life cycle. Recent advances in the research and development of small-molecule anti-human coronavirus therapies.",2020,"Pillaiyar, T.; Meenakshisundaram, S.; Manickam, M.",Drug Discovery Today,3003448227,#2569,
,CZI,Comparison of pulmonary availability and anti-inflammatory effect of dehydroandrographolide succinate via intratracheal and intravenous administration,10.1016/j.ejps.2020.105290,,,,"Dehydroandrographolide succinate (DAS) injection, which was approved in China for the treatment of viral pneumonia and upper respiratory tract infections, is often off-label used for nebulization therapy to avoid the adverse drug reactions associated with the injection. However, the aerodynamic properties and pulmonary fate of nebulized DAS was largely uninvestigated. In this study, the main objectives were to evaluate the in vitro aerodynamic deposition profiles of nebulizer generated aerosols and comparatively investigate the local drug availability and anti-inflammatory efficacy of DAS between intratracheal and intravenous dosing. The in vitro evaluation of aerodynamic characteristics and droplet size distribution showed more than 50% aerosol particles with size being < 5 μm, allowing the aerosols to reach the lower respiratory tract. Following intratracheal administration, the drug underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 47.3%. Compared to the intravenous delivery, the intratracheal administration dramatically increased the drug availability in the lung tissue in rats by more than 80-fold, leading to an improved and prolonged local anti-inflammatory efficacy in a lipopolysaccharide induced lung injury model in mice. The present results demonstrated that inhalation delivery of DAS is a convenient and effective alternative to intravenous injections.",2020,"Wei-Ya, Chen; Yuan-Song, Wang; Chun-Yu, Liu; Yu-Bin, Ji; Fei-Fei, Yang; Yong-Hong, Dr Liao",European Journal of Pharmaceutical Sciences,1978908825,#3102,
,CZI,A new pandemic out of China: the Wuhan 2019-nCoV coronavirus syndrome,10.1016/j.hlpt.2020.02.001,,,,,2020,"Singer, D. R. J.",Health Policy and Technology,3004825441,#1496,
,CZI,Strengthening ICU health security for a coronavirus epidemic,10.1016/j.iccn.2020.102812,,,,,2020,"Jansson, Miia; Liao, Xuelian; Rello, Jordi",Intensive and Critical Care Nursing,3004798505,#539,
,CZI,"Real-time forecasts of the COVID-19 epidemic in China from February 5th to February 24th, 2020",10.1016/j.idm.2020.02.002,,,,"The initial cluster of severe pneumonia cases that triggered the COVID-19 epidemic was identified in Wuhan, China in December 2019. While early cases of the disease were linked to a wet market, human-to-human transmission has driven the rapid spread of the virus throughout China. The Chinese government has implemented containment strategies of city-wide lockdowns, screening at airports and train stations, and isolation of suspected patients; however, the cumulative case count keeps growing every day. The ongoing outbreak presents a challenge for modelers, as limited data are available on the early growth trajectory, and the epidemiological characteristics of the novel coronavirus are yet to be fully elucidated.We use phenomenological models that have been validated during previous outbreaks to generate and assess short-term forecasts of the cumulative number of confirmed reported cases in Hubei province, the epicenter of the epidemic, and for the overall trajectory in China, excluding the province of Hubei. We collect daily reported cumulative confirmed cases for the 2019-nCoV outbreak for each Chinese province from the National Health Commission of China. Here, we provide 5, 10, and 15 day forecasts for five consecutive days, February 5th through February 9th, with quantified uncertainty based on a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model.Our most recent forecasts reported here, based on data up until February 9, 2020, largely agree across the three models presented and suggest an average range of 7409–7496 additional confirmed cases in Hubei and 1128–1929 additional cases in other provinces within the next five days. Models also predict an average total cumulative case count between 37,415 and 38,028 in Hubei and 11,588–13,499 in other provinces by February 24, 2020.Mean estimates and uncertainty bounds for both Hubei and other provinces have remained relatively stable in the last three reporting dates (February 7th – 9th). We also observe that each of the models predicts that the epidemic has reached saturation in both Hubei and other provinces. Our findings suggest that the containment strategies implemented in China are successfully reducing transmission and that the epidemic growth has slowed in recent days. Keywords: COVID-19, Coronavirus, China, Real-time forecasts, Phenomenological models",2020,"Chowell, K. Roosa; Lee, Y.; Luo, R.; Kirpich, A.; Rothenberg, R.; Hyman, J. M.; Yan, P.; G",Infectious Disease Modelling,3006028741,#1669,
,CZI,Chloroquine for the 2019 novel coronavirus SARS-CoV-2,10.1016/j.ijantimicag.2020.105923,,32070753,,,2020,"Colson, Philippe; Rolain, Jean-Marc; Raoult, Didier",International journal of antimicrobial agents,3006128040,#4035,
,CZI,Management of corona virus disease-19 (COVID-19): the Zhejiang experience,10.1016/j.ijantimicag.2020.105924,,32096367,,"The current epidemic situation of corona virus disease-19 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 inZhejiang Province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on ""Four-Anti and Two-Balance"" for clinical practice. The ""Four-Anti and Two-Balance""strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinarypersonalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in10% patients'blood samples at acute periodand 50% of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifyingcytokine storms and application of artificial liver blood purification system. The ""Four-Anti and Two-Balance""strategyeffectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviraleffects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favoredthe balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short periods of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis should be prescribed rationally and was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbialdysbiosis with decreasedprobiotics such as Lactobacillus and Bifidobacterium. Nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the SARS-CoV-2 infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience above and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.",2020,"Xu, Kaijin; Cai, Hongliu; Shen, Yihong; Ni, Qin; Chen, Yu; Hu, Shaohua; Li, Jianping; Wang, Huafen; Yu, Liang; Huang, He; Qiu, Yunqing; Wei, Guoqing; Fang, Qiang; Zhou, Jianying; Sheng, Jifang; Liang, Tingbo; Li, Lanjuan",Zhejiang Da Xue Xue Bao Yi Xue Ban,3006645647,#1909,
,CZI,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): the epidemic and the challenges,10.1016/j.ijantimicag.2020.105924,,,,"ABSTRACT Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously provisionally named 2019 novel coronavirus or 2019-nCoV) disease (COVID-19) in China at the end of 2019, has caused a large global outbreak and a major public health issue. As of February 11, 2020, data from the WHO has shown that more than 43,000 confirmed cases have been identified in 28 countries/regions, with more than 99% of the cases being detected in China. On January 30, 2020, WHO has declared COVID-19 as the sixth public health emergency of international concern. The SARS-CoV-2 is closely related to two bat-derived severe acute respiratory syndrome-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. It is spread by human-to-human transmission via droplets or direct contact, and infection has been estimated to have mean incubation period of 6.4 days and a basic reproduction number of 2.24-3.58. Among the patients with pneumonia caused by the SARS-CoV-2 (novel coronavirus pneumonia or Wuhan pneumonia), fever was the most common symptom, followed by cough. Bilateral lung involvement with ground glass opacity was the most common finding from computerized tomography images of the chest. Although the one case of SARS-CoV-2 pneumonia in the United States responding well to remdesivir, which is now undergoing a clinical trial in China. Currently, controlling infection to prevent the spread of the SARS-CoV-2 is the primary intervention being used. However, public health authorities should keep monitoring the situation closely, as the more we can learn about this novel virus and its associated outbreak, the better we can respond.",2020,"Lai, Chih-Cheng; Shih, Tzu-Ping; Ko, Wen-Chien; Tang, Hung-Jen; Hsueh, Po-Ren",International Journal of Antimicrobial Agents,3006645647,#1132,
,CZI,Chloroquine and hydroxychloroquine as available weapons to fight COVID-19,10.1016/j.ijantimicag.2020.105932,,,,,2020,"Colson, Philippe; Rolain, Jean-Marc; Lagier, Jean-Christophe; Brouqui, Philippe; Raoult, Didier",International Journal of Antimicrobial Agents,3006128040,#4597,
,CZI,Arguments in favor of remdesivir for treating SARS-CoV-2 infections,10.1016/j.ijantimicag.2020.105933,,,,,2020,"Ko, Wen-Chien; Rolain, Jean-Marc; Lee, Nan-Yao; Chen, Po-Lin; Huang, Ching-Tai; Lee, Ping-Ing; Hsueh, Po-Ren",International Journal of Antimicrobial Agents,3006645647,#4533,
,CZI,"Short-term effects of ambient PM1 and PM2.5 air pollution on hospital admission for respiratory diseases: Case-crossover evidence from Shenzhen, China",10.1016/j.ijheh.2019.11.001,,,,"Background Ambient PM1 (particulate matter with aerodynamic diameter ≤1 μm) is an important contribution of PM2.5 mass. However, little is known worldwide regarding the PM1-associated health effects due to a wide lack of ground-based PM1 measurements from air monitoring stations. Methods We collected daily records of hospital admission for respiratory diseases and station-based measurements of air pollution and weather conditions in Shenzhen, China, 2015–2016. Time-stratified case-crossover design and conditional logistic regression models were adopted to estimate hospitalization risks associated with short-term exposures to PM1 and PM2.5. Results PM1 and PM2.5 showed significant adverse effects on respiratory disease hospitalizations, while no evident associations with PM1–2.5 were identified. Admission risks for total respiratory diseases were 1.09 (95% confidence interval: 1.04 to 1.14) and 1.06 (1.02 to 1.10), corresponding to per 10 μg/m3 rise in exposure to PM1 and PM2.5 at lag 0–2 days, respectively. Both PM1 and PM2.5 were strongly associated with increased admission for pneumonia and chronic obstructive pulmonary diseases, but exhibited no effects on asthma and upper respiratory tract infection. Largely comparable risk estimates were observed between male and female patients. Groups aged 0–14 years and 45–74 years were significantly affected by PM1- and PM2.5-associated risks. PM-hospitalization associations exhibited a clear seasonal pattern, with significantly larger risks in cold season than those in warm season among some subgroups. Conclusions Our study suggested that PM1 rather than PM1–2.5 contributed to PM2.5-induced risks of hospitalization for respiratory diseases and effects of PM1 and PM2.5 mainly occurred in cold season.",2020,"Zhang, Yunquan; Ding, Zan; Xiang, Qianqian; Wang, Wei; Huang, Li; Mao, Feiyue",International Journal of Hygiene and Environmental Health,2989937665,#3088,
,CZI,First respiratory transmitted food borne outbreak?,10.1016/j.ijheh.2020.113490,,32088598,,"The world is faced with a remarkable coronavirus outbreak with epicentre in Wuhan, China. Altogether 40554 cases have been confirmed globally with novel coronavirus (SARS-CoV-2) until February 10, 2020. Rigorous surveillance in other countries is required to prevent further global expansion of the outbreak, but resolving the exact mechanism of the initial transmission events is crucial. Most initial cases had visited Huanan South Seafood Market in Wuhan selling also various exotic live animals. Based on the limited initial human-to-human transmission and timely clustering of cases in Huanan market among elderly men, coupled with knowledge that coronaviruses are derived from animals and relationship of SARS-CoV-2 to bat coronavirus, zoonotic transmission in the first instance is probable. To target the actions, similar epidemiological actions to human cases are needed with animal or food exposures. According to current information, an exceptionally wide contamination of seafood market might explain the initiation of the SARS-CoV-2 outbreak. Seafood tanks, air contamination by live animals or rodents are possibilities, but sold animals normally come from various sources. The mode of transmission may become clearer in future: usually in outbreak investigations, hindsight is easy, but for now information about the initial source of this outbreak is limited.",2020,"Jalava, Katri",Int J Hyg Environ Health,2092729099,#1832,
,CZI,The 2019 Novel Coronavirus Outbreak - A Global Threat,10.1016/j.ijid.2020.01.009,,32138488,,"The 2019 Novel Corona virus infection (COVID 19) is an ongoing public health emergency of international significance. There are significant knowledge gaps in the epidemiology, transmission dynamics, investigation tools and management. In this article, we review the available evidence about this disease. Every decade has witnessed the evolution of a new coronavirus epidemic since the last three decades. The varying transmission patterns, namely, nosocomial transmission and spread through mildly symptomatic cases is an area of concern. There is a spectrum of clinical features from mild to severe life threatening disease with major complications like severe pneumonia, ARDS, acute cardiac injury and septic shock. Presence of bilateral ground glass opacity and consolidation on imaging in appropriate clinical background should raise a suspicion about COVID 19. Poor prognostic factors include Multilobular infiltration on chest imaging, Lymphopenia, Bacterial co-infection, Smoking history, Chronic medical conditions like Hypertension and age >60 years (MuLBSTA score). Diagnosis is confirmed with PCR based testing of appropriate respiratory samples. Management is primarily supportive, with newer antivirals (lopinavir ritonavir and Remdesivir) under investigation. Role of steroids is still inconclusive. Standard infection control and prevention techniques should be followed. Vigilant screening of suspected cases and their contacts is important. Isolation of symptomatic cases and home quarantine of asymptomatic contacts is recommended. To conclude, controlling this highly transmissible disease requires international co-ordination.",2020,"Khot, W. Y.; Nadkar, M. Y.",The Journal of the Association of Physicians of India,2999409984,#4769,
,CZI,"Comments on ""Preliminary estimation of the basic reproduction number of novel Coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven Analysis in the early phase of the outbreak""",10.1016/j.ijid.2020.02.024,,,,,2020,"Dhungana, Hom Nath",International Journal of Infectious Diseases,3004397688,#1403,
,CZI,The basic reproduction number of novel coronavirus (2019-nCoV) estimation based on exponential growth in the early outbreak in China from 2019 to 2020: A reply to Dhungana,10.1016/j.ijid.2020.02.025,,,,,2020,"Zhao, Shi; Lin, Qianyin; Ran, Jinjun; Musa, Salihu S.; Yang, Guangpu; Wang, Weiming; Lou, Yijun; Gao, Daozhou; Yang, Lin; He, Daihai; Wang, Maggie H.",International Journal of Infectious Diseases,3004397688,#1345,
,CZI,2019-novel Coronavirus severe adult respiratory distress syndrome in two cases in Italy: An uncommon radiological presentation,10.1016/j.ijid.2020.02.043,,,,"Introduction Several recent case reports have described common early chest imaging findings of lung pathology caused by 2019 novel Coronavirus (SARS-COV2) which appear to be similar to those seen previously in SARS-CoV and MERS-CoV infected patients. Objective We present some remarkable imaging findings of the first two patients identified in Italy with COVID-19 infection travelling from Wuhan, China. The follow-up with chest X-Rays and CT scans was also included, showing a progressive adult respiratory distress syndrome (ARDS). Results Moderate to severe progression of the lung infiltrates, with increasing percentage of high-density infiltrates sustained by a bilateral and multi-segmental extension of lung opacities, were seen. During the follow-up, apart from pleural effusions, a tubular and enlarged appearance of pulmonary vessels with a sudden caliber reduction was seen, mainly found in the dichotomic tracts, where the center of a new insurgent pulmonary lesion was seen. It could be an early alert radiological sign to predict initial lung deterioration. Another uncommon element was the presence of mediastinal lymphadenopathy with short-axis oval nodes. Conclusions Although only two patients have been studied, these findings are consistent with the radiological pattern described in literature. Finally, the pulmonary vessels enlargement in areas where new lung infiltrates develop in the follow-up CT scan, could describe an early predictor radiological sign of lung impairment.",2020,"Albarello, Fabrizio; Pianura, Elisa; Di Stefano, Federica; Cristofaro, Massimo; Petrone, Ada; Marchioni, Luisa; Palazzolo, Claudia; Schininà, Vincenzo; Nicastri, Emanuele; Petrosillo, Nicola; Campioni, Paolo; Petersen, Eskild; Zumla, Alimuddin; Ippolito, Giuseppe",International Journal of Infectious Diseases,2087800735,#2446,
,CZI,"Is the Africa prepared for tackling the COVID-19 (SARS-CoV-2) epidemic? - lessons from past outbreaks, ongoing pan-African public health efforts, and implications for the future",10.1016/j.ijid.2020.02.049,,,,,2020,"Kapata, Nathan; Ihekweazu, Chikwe; Ntoumi, Francine; Tajudeen, Raji; Chanda-Kapata, Pascalina; Mwaba, Peter; Mukonka, Victor; Bates, Matthew; Tembo, John; Corman, Victor; Mfinanga, Sayoki; Asogun, Danny; Elton, Linzy; Arruda, Liã Bárbara; Thomason, Margaret J.; Mboera, Leonard; Yavlinsky, Alexei; Haider, Najmul; Simons, David; Hollmann, Lara; Lule, Swaib A.; Veas, Francisco; Abdel Hamid, Muzamil Mahdi; Dar, Osman; Edwards, Sarah; Vairo, Francesco; McHugh, Timothy D.; Drosten, Christian; Kock, Richard; Ippolito, Giuseppe; Zumla, Alimuddin",International Journal of Infectious Diseases,3006645647,#2857,
,CZI,Recurrence of positive SARS-CoV-2 RNA in COVID-19: A case report,10.1016/j.ijid.2020.03.003,,,,"The ongoing outbreak of COVID-19 that began in Wuhan, China, has constituted a Public Health Emergency of International Concern, with cases confirmed in multiple countries. Currently patients are the main source of infection. We report a confirmed case of COVID-19 whose oropharyngeal swab test of SARS-CoV-2 RNA turned positive in convalescence. This case highlights the importance of dynamic surveillance of SARS-CoV-2 RNA for infectivity assessment.",2020,"Chen, Dabiao; Xu, Wenxiong; Lei, Ziying; Huang, Zhanlian; Liu, Jing; Gao, Zhiliang; Peng, Liang",International Journal of Infectious Diseases,3006645647,#4608,
,CZI,New regulatory strategies to manage medicines shortages in Europe,10.1016/j.ijpharm.2020.119171,,,,"Medicine shortages have been spreading in European countries. In many cases, the unavailability of medicinal products has a substantial impact on the capability of National Healthcare Systems in ensuring the continuity of care. Shortages originate from multifactorial causes. In particular, they can be due to supply-related factors (e.g., manufacturing issues, regulatory issues, logistics, distribution) and demand-related ones (e.g., fluctuating drug demand, parallel market, tendering, price and reimbursement policies). However, some extraordinary geopolitical events (e.g., Brexit) may also affect medicines’ availability. The capability of European Regulatory Authorities and other stakeholders, which are involved in the pharmaceutical distribution chain and the healthcare assistance services, to define suitable problem-solving strategies has been limited for years by the fragmentation of the European regulatory framework, starting from the lack of a univocal definition of a medicine shortage. Only in 2019, the EMA and HMA joint task force released the first harmonized “shortage” definition in the European Economic Area (EEA) and guidance on public communication. This manuscript aims to review the current European regulatory framework on medicine shortages. To support the activities of regulators, manufacturers and other healthcare professionals, an algorithm was also proposed to be used as a harmonized procedure to determine the shortage/unavailability impact on public health and to rationalize the problem-solving strategies adopted in all different settings.",2020,"Musazzi, Umberto M.; Di Giorgio, Domenico; Minghetti, Paola",International Journal of Pharmaceutics,2942764320,#3143,
,CZI,World Health Organization declares Global Emergency: A review of the 2019 Novel Coronavirus (COVID-19),10.1016/j.ijsu.2020.02.034,,,,"An unprecedented outbreak of pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December of 2019. A novel coronavirus was identified as the causative agent and was subsequently termed COVID-19 by the World Health Organization (WHO). Considered a relative of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), COVID-19 is a betacoronavirus that affects the lower respiratory tract and manifests as pneumonia in humans. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 50,580 laboratory-confirmed cases and 1,526 deaths worldwide. In response to this global outbreak, we summarise the current state of knowledge surrounding COVID-19.",2020,"Sohrabi, Catrin; Alsafi, Zaid; O’Neill, Niamh; Khan, Mehdi; Kerwan, Ahmed; Al-Jabir, Ahmed; Iosifidis, Christos; Agha, Riaz",International Journal of Surgery,2965809604,#2395,
,CZI,Tuberculosis and novel Wuhan coronavirus infection: pathological interrelationship,10.1016/j.ijtb.2020.02.004,,,,,2020,"Yasri, Sora; Wiwanitkit, Viroj",Indian Journal of Tuberculosis,1932726324,#2084,
,CZI,What are we doing in the dermatology outpatient department amidst the raging of 2019-nCoV?,10.1016/j.jaad.2020.02.030,,,,,2020,"Chen, Yusha; Pradhan, Sushmita; Xue, Siliang",Journal of the American Academy of Dermatology,3006436003,#1156,
,CZI,Letter from the Editor,10.1016/j.jaad.2020.02.031,,,,,2020,"Elston, Dirk M.",Journal of the American Academy of Dermatology,2963953047,#983,
,CZI,Coronavirus (COVID-19) Outbreak: What the Department of Radiology Should Know,10.1016/j.jacr.2020.02.008,,32092296,,"In December 2019, a novel coronavirus (COVID-19) pneumonia emerged in Wuhan, China. Since then, this highly contagious COVID-19 has been spreading worldwide, with a rapid rise in the number of deaths. Novel COVID-19-infected pneumonia (NCIP) is characterized by fever, fatigue, dry cough, and dyspnea. A variety of chest imaging features have been reported, similar to those found in other types of COVID-19 syndromes. The purpose of the present review is to briefly discuss the known epidemiology and the imaging findings of COVID-19 syndromes, with a focus on the reported imaging findings of NCIP. Moreover, the authors review precautions and safety measures for radiology department personnel to manage patients with known or suspected NCIP. Implementation of a robust plan in the radiology department is required to prevent further transmission of the virus to patients and department staff members.",2020,"Kooraki, Soheil; Hosseiny, Melina; Myers, Lee; Gholamrezanezhad, Ali",Journal of the American College of Radiology : JACR,3005943294,#3714,
,CZI,Psychological intervention in oral patients in novel coronavirus pneumonia outbreak period,10.1016/j.jamda.2007.10.003,,,,"Public health emergencies have an impact on the public mental health. The outbreak of the novel coronavirus has affected the normal diagnosis and treatment services in oral medical institutions across the country. Delay of non-emergency dental service will have a potential impact on the experience, cognition, treatment and rehabilitation of patients with oral diseases. Through literature review, this paper reviewed the oral psychosomatic diseases closely related to patients' psychological state, such as oral mucosal disease, temporomandibular joint disease, bruxism, periodontal disease and so on. It was believed that these patients might be more susceptible to the impact of stress events, and dental specialists should pay more attention to them. At the same time, this paper analyzes the possible psychological stress symptoms of patients with different oral diseases, and puts forward suggestions for remote consultation and emergency treatment of dentists. From the perspective of social role, dentists not only played the role of expert in dental home professional guidance, but also played the role of psychological counseling for patients.",2020,"QU, Xing; ZHOU, Xue Dong",Chinese Journal of Stomatology,1991886054,#1941,
,CZI,Coronaphobia: Fear and the 2019-nCoV Outbreak,10.1016/j.janxdis.2020.102196,,,,,2020,"Asmundson, Gordon J. G.; Taylor, Steven",Journal of Anxiety Disorders,3005195331,#629,
,CZI,The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak,10.1016/j.jaut.2020.102433,,,,"Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the causative agent of a potentially fatal disease that is of great global public health concern. Based on the large number of infected people that were exposed to the wet animal market in Wuhan City, China, it is suggested that this is likely the zoonotic origin of COVID-19. Person-to-person transmission of COVID-19 infection led to the isolation of patients that were subsequently administered a variety of treatments. Extensive measures to reduce person-to-person transmission of COVID-19 have been implemented to control the current outbreak. Special attention and efforts to protect or reduce transmission should be applied in susceptible populations including children, health care providers, and elderly people. In this review, we highlights the symptoms, epidemiology, transmission, pathogenesis, phylogenetic analysis and future directions to control the spread of this fatal disease.",2020,"Rothan, Hussin A.; Byrareddy, Siddappa N.",Journal of Autoimmunity,3006645647,#2415,
,CZI,The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China,10.1016/j.jaut.2020.102434,,,,"The 2019-nCoV is officially called SARS-CoV-2 and is the cause of the disease named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002–2003 and MERS in 2012. While human strains of Coronavirus are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Extreme quarantine measures, including sealing off large cities, closing borders and confining people to their homes, were instituted in January 2020 to prevent spread of the virus, but by that time much of the damage had been done, as human-human transmission became evident. While these quarantine measures are necessary and have prevented a historical disaster along the lines of the Spanish flu, earlier recognition and earlier implementation of quarantine measures may have been even more effective. Lessons learned from SARS resulted in faster determination of the nucleic acid sequence and a more robust quarantine strategy. However, it is clear that finding an effective antiviral and developing a vaccine are still significant challenges. The costs of the epidemic are not limited to medical aspects, as the virus has led to significant sociological, psychological and economic effects globally. Unfortunately, emergence of SARS-CoV-2 has led to numerous reports of Asians being subjected to racist behavior and hate crimes across the world.",2020,"Yang, Yongshi; Peng, Fujun; Wang, Runsheng; Guan, Kai; Jiang, Taijiao; Xu, Guogang; Sun, Jinlyu; Chang, Christopher",Journal of Autoimmunity,2999409984,#4387,
,CZI,"Rapid random access detection of the novel SARS-coronavirus-2 (SARS-CoV-2, previously 2019-nCoV) using an open access protocol for the Panther Fusion",10.1016/j.jcv.2020.104305,,,,,2020,"Cordes, Anne K.; Heim, Albert",Journal of Clinical Virology,1982149511,#2656,
,CZI,2019-novel coronavirus outbreak: A new challenge,10.1016/j.jgar.2020.02.021,,,,"Objectives Following the public health emergency declared by the World Health Organization and the recent outbreak by 2019-nCoV in China and through other 29 countries, we aimed to summarize the clinical aspects of novel beta-coronavirus infection and its possible clinical presentations together with suggested therapeutic algorithms for patients who may require antibiotic treatment. Methods We reviewed the currently available literature of microbiologically confirmed infections by 2019-ConV (or COVID-19) occurred at the time of writing (13 February 2020). A literature search was performed using the PubMed database and the Cochrane library. Search terms included ""novel coronavirus"" or ""2019-nCoV"" or “COVID-19”. Results Published cases occurred mostly in males (age ranged from 8 to 92). Cardiovascular, digestive and endocrine system diseases were commonly reported, except previous chronic pulmonary diseases (e.g., COPD, asthma, bronchiectasis) that were surprisingly underreported. Fever was presented in all the case series available, flanked by cough, dyspnea, myalgias and fatigue. Multiple bilateral lobular and subsegmental areas of consolidation or bilateral ground-glass opacities were the main reported radiological features of 2019-nCoV, at least in the early phases of disease. Conclusions The new 2019-nCoV epidemics is mainly associated with respiratory disease and few extrapulmonary signs. However, there is a low rate of associated pre-existing respiratory comorbidities.",2020,"Lupia, Tommaso; Scabini, Silvia; Pinna, Simone Mornese; Di Perri, Giovanni; De Rosa, Francesco Giuseppe; Corcione, Silvia",Journal of Global Antimicrobial Resistance,3003218364,#5473,
,CZI,Identification of potential cross-protective epitope between 2019-nCoV and SARS virus,10.1016/j.jgg.2020.01.003,,,,,2020,"Qiu, Tianyi; Mao, Tiantian; Wang, Yuan; Zhou, Mengdi; Qiu, Jingxuan; Wang, Jianwei; Xu, Jianqing; Cao, Zhiwei",Journal of Genetics and Genomics,3004310457,#121,
,CZI,Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines,10.1016/j.jgg.2020.02.001,,,,,2020,"Liu, Xin; Wang, Xiu-Jie",Journal of Genetics and Genomics,3006049090,#757,
,CZI,Preparedness and proactive infection control measures against the emerging novel coronavirus in China,10.1016/j.jhin.2020.01.010,,,,,2020,"Cheng, V. C. C.; Wong, S. C.; To, K. K. W.; Ho, P. L.; Yuen, K. Y.",Journal of Hospital Infection,3000694338,#3198,
,CZI,Novel coronavirus is putting the whole world on alert,10.1016/j.jhin.2020.01.019,,,,,2020,"Khan, S.; Ali, A.; Siddique, R.; Nabi, G.",Journal of Hospital Infection,3005427413,#226,
,CZI,Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents,10.1016/j.jhin.2020.01.022,,,,"Summary Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62–71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.",2020,"Kampf, G.; Todt, D.; Pfaender, S.; Steinmann, E.",Journal of Hospital Infection,3005057892,#3162,
,CZI,"Novel coronavirus, poor quarantine, and the risk of pandemic",10.1016/j.jhin.2020.02.002,,,,,2020,"Khan, S.; Siddique, R.; Ali, A.; Xue, M.; Nabi, G.",Journal of Hospital Infection,3005588847,#763,
,CZI,Novel coronavirus pneumonia emergency in Zhuhai: impact and challenges,10.1016/j.jhin.2020.02.005,,,,,2020,"Jin, Hao; Lu, Ligong; Liu, Junwei; Cui, Min",Journal of Hospital Infection,3006132735,#966,
,CZI,The non-contact handheld cutaneous infra-red thermometer for fever screening during the COVID-19 global emergency,10.1016/j.jhin.2020.02.010,,,,,2020,"Aw, Dr Junjie",Journal of Hospital Infection,2319752646,#1700,
,CZI,Journal of Hospital Infection to move to Article-Based Publishing,10.1016/j.jhin.2020.02.013,,,,,2020,,Journal of Hospital Infection,2886249692,#3225,
,CZI,COVID-19 in medical personnel: observation from Thailand,10.1016/j.jhin.2020.02.016,,32114054,,,2020,"Joob, Beuy; Wiwanitkit, Viroj",J Hosp Infect,2403835304,#3061,
,CZI,Integrated infection control strategy to minimize nosocomial infection of corona virus disease 2019 among ENT healthcare workers,10.1016/j.jhin.2020.02.018,,,,,2020,"Lu, Dan; Wang, Haiyang; Yu, Rong; HuiYang; Zhao, Yu",Journal of Hospital Infection,2010285947,#2893,
,CZI,"Practical experiences and suggestions on the eagle-eyed observer, a novel promising role for controlling nosocomial infection of the COVID-19 outbreak",10.1016/j.jhin.2020.02.020,,,,,2020,"Peng, Jianhui; Ren, Nina; Wang, Mingke; Zhang, Gangqing",Journal of Hospital Infection,2093686886,#4477,
,CZI,Association between 2019-nCoV transmission and N95 respirator use,10.1016/j.jhin.2020.02.021,,,,,2020,"Wang, Xinghuan; Pan, Zhenyu; Cheng, Zhenshun",Journal of Hospital Infection,3004826757,#4417,
,CZI,Effective strategies to prevent coronavirus disease-2019 (COVID-19) outbreak in hospital,10.1016/j.jhin.2020.02.022,,,,,2020,"Lee, Ing-Kit; Wang, Chih-Chi; Lin, Meng-Chih; Kung, Chia-Te; Lan, Kuo-Chung; Lee, Chien-Te",Journal of Hospital Infection,3005657121,#4526,
,CZI,Understanding the emerging coronavirus: what it means for health security and infection prevention,10.1016/j.jhin.2020.02.023,,,,,2020,"Peters, Alexandra; Vetter, Pauline; Guitart, Chloé; Lotfinejad, Nasim; Pittet, Didier",Journal of Hospital Infection,2079438251,#4475,
,CZI,Diagnosis of SARS-CoV-2 Infection based on CT scan vs. RT-PCR: Reflecting on Experience from MERS-CoV,10.1016/j.jhin.2020.03.001,,,,,2020,"Al-Tawfiq, Jaffar A.; Memish, Ziad A.",Journal of Hospital Infection,2168296380,#4635,
,CZI,Exploring the reasons for healthcare workers infected with novel coronavirus disease 2019 (COVID-19) in China,10.1016/j.jhin.2020.03.002,,,,,2020,"Wang, Jiancong; Zhou, Mouqing; Liu, Fangfei",Journal of Hospital Infection,3001118548,#4420,
,CZI,Duration of quarantine in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a question needing an answer,10.1016/j.jhin.2020.03.003,,,,"In December 2019 a new form of pneumonia was observed in the Chinese province of Hubei.[1] The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was subsequently identified as responsible of this condition, defined coronavirus disease (COVID-19).[2] The virus has now spread outside Chinese borders with 82,297 cases and 2,804 deaths worldwide at the 26th of February.[3] After infection, symptoms appear after an incubation time of 3-5 days, with 80% of those infected developing a mild disease, 15% a severe disease and 5% will require support in intensive care unit (ICU).[4] Overall, the estimated case-fatality rate is comprised between 0.4% and 2.9% and the basic reproduction number is approximately 3.28.[4,5] SARS-CoV-2 is a new pathogen for humankind and any type of immune protection exist, thus everybody can be potentially infected. Moreover, no primary prophylaxis measures (vaccination) nor effective treatments are available. If the above represented percentages are applied to the worldwide populations, it appears clear why any measure should be considered to avoid a further diffusion of the virus and prevent the saturation and collapse of health systems and the most catastrophic pandemic since 1919 Spanish flu. Isolation of those affected and the use of personal protective equipment (PPE) are the mainstay to block transmission of this pathogen, which is presumed through respiratory droplets. A 14 days quarantine is applied to subjects coming from endemic areas or who had contact with confirmed cases. It is assumed that, if in this period the subject does not develop any sign or symptoms compatible with COVID-19, he is not infected and thus the quarantine can be removed, and the subject returned to the community. Domiciliary quarantine of 14 days since a positive test is applied also for patients with a diagnosed mild disease who did not need medical support. These rules are effective in controlling infections in the community, but several doubts arise when it is necessary to transpose them in the hospital setting. Hospitals are indeed a delicate place in epidemics: they collect fragile persons who can be exposed to the virus and are subsequently readmitted to the community thus spreading the infection. Indeed, the ongoing outbreak in Northern Italy has been linked to a single infected patient who accessed to a community hospital where he transmitted the virus to several other patients and health-care operators.[6] Moreover, the isolation of patients in the hospital setting impose a significant burden in terms of PPE used by the health-care operators, space dedicated and time employed in their management. Even more complex is the situation of patients in ICU, where viral spreading is facilitated by endotracheal tubes and manoeuvres performed on the respiratory tract. Therefore, a clear definition of the infectiousness timing and intensity of viral spreading is mandatory to alleviate the burden on the health-care system. Unfortunately, the data available on the topic are scarce and composed only of measurements of viral shedding, without an assessment of the infectivity. Kim et al.[7] assessed the viral load kinetics of SARS-CoV-2 in upper and lower respiratory tract materials in the first two confirmed patients in Korea. They employed real-time reverse transcriptase polymerase chain reaction (rRT-PCR) to detect SARS-CoV-2 and converted cycle threshold (CT) values of rRT-PCR into RNA copy number. The detection limit of rRT-PCR was 2,690 copies/mL. Overall, viral load above detection limit was detected until 14 and 25 days after symptoms onset and for 13 and 11 days after the first detection, respectively.[7] Of note, both patients received treatment with lopinavir/ritonavir. Instead, Zou and colleagues analysed viral load in repeated nasal and throat swabs obtained from the 17 symptomatic patients.[8] They also employed rRT-PCR and considered a CT of 40 as detection limit. Higher viral loads were observed in nasal swabs and in samples collected soon after symptoms onset. Overall, only two patients prese ted positive samples, and only in nasal swab, 14 days after symptoms onset, and with low viral load. In conclusion, a larger amount of data about duration of viral spreading and infectivity in hospitalized patients, especially in ICU, is badly needed to better define quarantine period and avoid nosocomial transmission. Before their availability, the canonical 14 days period of quarantine should be respected.",2020,"Lombardi, Andrea; Bozzi, Giorgio; Mangioni, Davide; Muscatello, Antonio; Peri, Anna Maria; Taramasso, Lucia; Ungaro, Riccardo; Bandera, Alessandra; Gori, Andrea",Journal of Hospital Infection,3005788786,#5464,
,CZI,"Emergence of a novel coronavirus causing respiratory illness from Wuhan, China",10.1016/j.jinf.2020.01.014,,,,,2020,"Tang, Julian W.; Tambyah, Paul A.; Hui, David S.C.",Journal of Infection,3003843886,#39,
,CZI,Genetic diversity and potential recombination between ferret coronaviruses from European and American lineages,10.1016/j.jinf.2020.01.016,,,,,2020,"Xu, Yifei",Journal of Infection,3005204082,#2098,
,CZI,Emergence of SARS-like Coronavirus poses new challenge in China,10.1016/j.jinf.2020.01.017,,,,,2020,"Wang, Ruichen; Zhang, Xu; Irwin, David M.; Shen, Yongyi",Journal of Infection,3003671106,#45,
,CZI,The continuous evolution and dissemination of 2019 novel human coronavirus,10.1016/j.jinf.2020.02.001,,,,,2020,"Zhang, Jiahao; Ma, Kaixiong; Li, Huanan; Liao, Ming; Qi, Wenbao",Journal of Infection,3003886061,#1434,
,CZI,Novel coronavirus (2019-nCoV) cases in Hong Kong and implications for further spread,10.1016/j.jinf.2020.02.002,,,,,2020,"Kwok, Kin On; Wong, Valerie; Wei, Vivian Wan In; Wong, Samuel Yeung Shan; Tang, Julian Wei-Tze",Journal of Infection,3006078464,#1599,
,CZI,Clinical Features of Atypical 2019 Novel Coronavirus Pneumonia with an initially Negative RT-PCR Assay,10.1016/j.jinf.2020.02.008,,,,,2020,"Hao, Wendong",Journal of Infection,3005656138,#1633,
,CZI,Recent insights into 2019-nCoV: a brief but comprehensive review,10.1016/j.jinf.2020.02.010,,,,"A novel coronavirus designated as 2019-nCoV hit the central Chinese city of Wuhan in late December 2019, and subsequently spread rapidly to all provinces of China and multiple countries. Up to 0:00 am February 9, 2020, a total of 37,287 cases have been confirmed infection of 2019-nCoV in China mainland, and 302 cases have also been cumulatively reported from 24 countries. According to the latest data, a total of 813 deaths occurred in China mainland, with the mortality reaching approximately 2.2%. At present, there is no vaccine or specific drugs for human coronavirus, so that it's critical to understand the nature of the virus and its clinical characteristics to response to the 2019-nCoV outbreak. Thus, we summarize the not much but timely reports on the 2019-nCoV in the present study, briefly but comprehensively.",2020,"Han, Qingmei; Lin, Qingqing; Jin, Shenhe; You, Liangshun",Journal of Infection,2978182211,#1986,
,CZI,Chinese medical personnel against the 2019-nCoV,10.1016/j.jinf.2020.02.011,,,,,2020,"Feng, Zhan-hui; Cheng, Yong-ran; Chen, Juan; Ye, Lan; Zhou, Meng-Yun; Wang, Ming-Wei",Journal of Infection,2414960577,#1646,
,CZI,Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV,10.1016/j.jinf.2020.02.013,,,,,2020,"Li, Rui; Qiao, Songlin; Zhang, Gaiping",Journal of Infection,2082231154,#1584,
,CZI,Trend and forecasting of the COVID-19 outbreak in China,10.1016/j.jinf.2020.02.014,,,,,,"Li, Qiang; Feng, Wei; Quan, Ying-Hui",Journal of Infection,3005902168,#2988,
,CZI,"Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19):A multi-center study in Wenzhou city, Zhejiang, China",10.1016/j.jinf.2020.02.016,,,,"Background Little is known about COVID-19 outside Hubei. The aim of this paper was to describe the clinical characteristics and imaging manifestations of hospitalized patients with confirmed COVID-19 infection in Wenzhou, Zhejiang, China. Methods In this retrospective cohort study, 149 RT-PCR confirmed positive patients were consecutively enrolled from January 17th to February 10th, 2020 in three tertiary hospitals of Wenzhou. Outcomes were followed up until Feb 15th, 2020. Findings A total of 85 patients had Hubei travel/residence history, while another 49 had contact with people from Hubei and 15 had no traceable exposure history to Hubei. Fever, cough and expectoration were the most common symptoms, 14 patients had decreased oxygen saturation, 33 had leukopenia, 53 had lymphopenia, and 82 had elevated C reactive protein. On chest computed tomography, lung segments 6 and 10 were mostly involved. A total of 287 segments presented ground glass opacity, 637 presented mixed opacity and 170 presented consolidation. Lesions were more localized in the peripheral lung with a patchy form. No significant difference was found between patients with or without Hubei exposure history. Seventeen patients had normal CT on admission of these, 12 had negative findings even10 days later. Interpretation Most patients presented with a mild infection in our study. The imaging pattern of multifocal peripheral ground glass or mixed opacity with predominance in the lower lung is highly suspicious of COVID-19 in the first week of disease onset. Nevetheless, some patients can present with a normal chest finding despite testing positive for COVID-19. Funding: We did not receive any fundings.",2020,"Yang, Wenjie; Cao, Qiqi; Qin, Le; Wang, Xiaoyang; Cheng, Zenghui; Pan, Ashan; Dai, Jianyi; Sun, Qingfeng; Zhao, Fengquan; Qu, Jieming; Yan, Fuhua",Journal of Infection,3005477624,#2089,
,CZI,Characteristics of COVID-19 infection in Beijing,10.1016/j.jinf.2020.02.018,,,,"Background : Since the first case of a novel coronavirus (COVID-19) infection pneumonia was detected in Wuhan, China, a series of confirmed cases of the COVID-19 were found in Beijing. We analyzed the data of 262 confirmed cases to determine the clinical and epidemiological characteristics of COVID-19 in Beijing. Methods : We collected patients who were transferred by Beijing Emergency Medical Sevice to the designated hospitals. The information on demographic, epidemiological, clinical, laboratory test for the COVID-19 virus, diagnostic classification, cluster case and outcome were obtained. Furthermore we compared the characteristics between severe and common confirmed cases which including mild cases, no-pneumonia cases and asymptomatic cases, and we also compared the features between COVID-19 and 2003 SARS. Findings : By Feb 10, 2020, 262 patients were transferred from the hospitals across Beijing to the designated hospitals for special treatment of the COVID-19 infected by Beijing emergency medical service. Among of 262 patients, 46 (17.6%) were severe cases, 216 (82.4%) were common cases, which including 192 (73.3%) mild cases, 11(4.2%) non-pneumonia cases and 13 (5.0%) asymptomatic cases respectively. The median age of patients was 47.5 years old and 48.5% were male. 192 (73.3%) patients were residents of Beijing, 50 (26.0%) of which had been to Wuhan, 116 (60.4%) had close contact with confirmed cases, 21 (10.9%) had no contact history. The most common symptoms at the onset of illness were fever (82.1%), cough (45.8%), fatigue (26.3%), dyspnea (6.9%) and headache (6.5%). The median incubation period was 6.7 days, the interval time from between illness onset and seeing a doctor was 4.5 days. As of Feb 10, 17.2% patients have discharged and 81.7% patients remain in hospital in our study, the fatality of COVID-19 infection in Beijing was 0.9%. Interpretation : On the basis of this study, we provided the ratio of the COVID-19 infection on the severe cases to the mild, asymptomatic and non-pneumonia cases in Beijing. Population was generally susceptible, and with a relatively low fatality rate. The measures to prevent transmission was very successful at early stage, the next steps on the COVID-19 infection should be focused on early isolation of patients and quarantine for close contacts in families and communities in Beijing. Funding Beijing Municipal Science and Technology Commission and Ministry of Science and Technology.",2020,"Tian, Sijia; Hu, Nan; Lou, Jing; Chen, Kun; Kang, Xuqin; Xiang, Zhenjun; Chen, Hui; Wang, Dali; Liu, Ning; Liu, Dong; Chen, Gang; Zhang, Yongliang; Li, Dou; Li, Jianren; Lian, Huixin; Niu, Shengmei; Zhang, Luxi; Zhang, Jinjun",Journal of Infection,3005679569,#2148,
,CZI,Simulating and Forecasting the Cumulative Confirmed Cases of SARS-CoV-2 in China by Boltzmann Function-based Regression Analyses,10.1016/j.jinf.2020.02.019,,,,,2020,"Fu, Xinmiao; Ying, Qi; Zeng, Tieyong; Long, Tao; Wang, Yan",Journal of Infection,3006355661,#1993,
,CZI,Novel coronavirus disease (Covid-19): the first two patients in the UK with person to person transmission,10.1016/j.jinf.2020.02.020,,,,,2020,"Lillie, Patrick J.; Samson, Anda; Li, Ang; Adams, Kate; Capstick, Richard; Barlow, Gavin D.; Easom, Nicholas; Hamilton, Eve; Moss, Peter J.; Evans, Adam; Ivan, Monica; Team, P. H. E. Incident; Taha, Yusri; Duncan, Christopher J. A.; Schmid, Matthias L.",Journal of Infection,3006007867,#2881,
,CZI,Clinical and CT imaging features of 2019 novel coronavirus disease (COVID-19),10.1016/j.jinf.2020.02.022,,,,"Tang JW, et al. and colleagues have written to this Journal describing the emergence of 2019 novel coronavirus disease (COVID-19).1 We have had an opportunity to examine in detail the chest computed tomography (CT) findings in cases with microbiologically confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, to familiarize radiologists and clinicians with the imaging manifestations of this new outbreak. Meanwhile, we also studied the clinical characteristics of the cases, combined with CT manifestations, to provide more clues for the correct diagnosis of the disease. Six female patients (P1-P6) aged from 27 to 63 years were referred to the fever clinic of our hospital. None of the patients had underlying diseases such as diabetes, malignant tumour or respiratory disease. Among the 6 cases, 5 (P1-P5) had a history of exposure to Wuhan or Hubei, and P6 had no clear epidemiological history. All the patients performed oropharyngeal swabs test and confirmed as COVID-19. Common respiratory viruses, mycoplasma and chlamydia were negative. For patients’ venous blood tests at disease onset, as given in (Table 1), we found that leucocytes, lymphocytes and percentage were slightly decreased or normal, eosinophil count and percentage were slightly decreased in 4 cases and normal in 2 cases. Additionally, 4 days later, P1 reperformed the follow-up hematologic examination. Compared with the blood test at disease onset, the results showed that the eosinophil count was still below the normal range, which was even lower than the first time.",,"Zhu, Ying; Liu, Yang-Li; Li, Zi-Ping; Kuang, Jian-Yi; Li, Xiang-Min; Yang, You-You; Feng, Shi-Ting",Journal of Infection,3005929298,#3478,
,CZI,"Corona Virus Disease 2019, a growing threat to children?",10.1016/j.jinf.2020.02.024,,,,,,"Yang, Pu; Liu, Pin; Li, Dan; Zhao, Dongchi",Journal of Infection,3006645647,#3480,
,CZI,Insights into the cross-species evolution of 2019 novel coronavirus,10.1016/j.jinf.2020.02.025,,,,"Recent study reported in this journal that the threats of continuous evolution and dissemination of 2019 human coronaviruses.1 Since its emergence in December 2019, a “seventh” member of the family of 2019 human coronavirus named “SARS-CoV-2” was responsible for an outbreak of coronavirus disease (COVID-19) in Wuhan, China.2 As of February 23, 2020, China had reported more than 77,042 confirmed cases of SARS-CoV-2, with 2,445 fatalities and counting (http://www.nhc.gov.cn). Strikingly, SARS-CoV-2 had been transmitted rapidly in more than 29 countries to date (https://www.who.int), including Asia, Europe, North America, Africa, and Oceania, posing serious concerns about its pandemic potential. Despite of droplet and contact transmissions of SARS-CoV-2, recent studies demonstrated that SARS-CoV-2 might be transmitted via aerosol and fecal–oral routes 3 (Figure 1), which needs to be paid attention in particular.",,"Zhang, Jiahao; Jia, Weixin; Zhu, Junhai; Li, Bo; Xing, Jinchao; Liao, Ming; Qi, Wenbao",Journal of Infection,3003886061,#3479,
,CZI,Identification of the hyper-variable genomic hotspot for the novel coronavirus SARS-CoV-2,10.1016/j.jinf.2020.02.027,,,,"A recent study in this journal studied the genomes of the novel SARS-like coronavirus (SARS-CoV-2) in China and suggested that the SARS-CoV-2 had undergone genetic recombination with SARS-related CoV1. By February 14, 2020, a total of 66,576 confirmed cases of COVID-19, people infected with SARS-CoV-2, were reported in China, leading to 1,524 deaths, per the Chinese CDC (http://2019ncov.chinacdc.cn/2019-nCoV/). Several full genomic sequences of this virus have been released for the study of its evolutionary origin and molecular characteristics2, 3, 4. Here, we analyzed the potential mutations that may have evolved after the virus became epidemic among humans and also the mutations resulting in the human adaptation. The sequences of BetaCoV were downloaded on February 3, 2020 from the GISAID platform5. A total of 58 accessions were available, among which BetaCoV/bat/Yunnan/RaTG13/2013 is a known close relative of SARS-CoV-2. Four accessions, namely, BetaCov/Italy/INM1/2020, BetaCov/Italy/INM2/2020, BetaCoV/Kanagawa/1/2020, and BetaCoV/USA/IL1/2020, were excluded because of the short-truncated sequences or multiple ambiguous nucleotides. A total of 54 accessions (Supplementary table 1) isolated from humans were utilized in the following analysis. The sequences NC_004718.3 of SARS coronavirus6 genes were utilized to define the protein products of SARS-CoV-2. The protein sequences of ORF1ab, S, E, M, and N genes were translated, and all of the loci without experimental evidences were excluded. First, the protein sequences of SARS-CoV-2 were compared with RaTG13, human SARS (NC_004718.3), bat SARS (DQ022305.2), and human MERS (NC_019843.3) by calculating the similarity in a given sliding window (Figure 1A). The sliding window was set to 500 for ORF1ab and S, and to 50 for proteins E, M, and N considering their short length. SARS-CoV-2 were highly similar to RaTG13 isolated from bats, showing 96% identity based on the whole-nucleotide sequences and 83% based on the protein sequences, suggesting a bat zoonotic origin of SARS-CoV-2. ORF1a, and the head of S seemed to have diverged from other beta coronaviruses.",,"Wen, Feng; Yu, Hai; Guo, Jinyue; Li, Yong; Luo, Kaijian; Huang, Shujian",Journal of Infection,3005538648,#4195,
,CZI,Clinical manifestations and outcome of SARS-CoV-2 infection during pregnancy,10.1016/j.jinf.2020.02.028,,,,"Tang and colleagues, in this Journal, drew readers attention to emerging COVID19.1 We focused on the pregnant COVID19 patients. Given the maternal physiologic and immune function changes in pregnancy,2 pregnant individuals might face greater risk of getting infected by SARS-CoV-2 and might have more complicated clinical events. We described epidemiological, clinical characteristics, pregnancy and perinatal outcomes of all hospitalized pregnant patients diagnosed with COVID-19 in China. We identified all hospitalized pregnant patients with laboratory-confirmed SARS-CoV-2 infection between December 8, 2019, and February 25, 2020 officially reported by the central government, in areas outside Wuhan, China. Information including age, geographic location, epidemiological history, prenatal course, maternal and newborn hospital course, discharge data and outcome were obtained by Centers for Disease Control and Prevention and Local Health Commission. When necessary, we attempted to contact local hospital or patients by telephone to supply missing information. This investigation was part of an emergency public health outbreak investigation and therefore not subject to institutional review board. There were a total of 13 Chinese patients with SARS-CoV-2 admitted to hospitals outside of Wuhan (Table 1). There were 3 patients from Zhejiang, 3 from other cities of Hubei and 1 each from Fujian, Shanxi, Beijing, Guangdong, Jiangxi, Heilongjiang and Anhui. The maternal age ranged between 22 to 36 years. Two women were less than 28 weeks of gestation and the other 11 patients were in their third trimesters at presentation. None of the patients had underlying medical disease.",,"Liu, Yangli; Chen, Haihong; Tang, Kejing; Guo, Yubiao",Journal of Infection,2279386236,#3797,
,CZI,Lymphopenic community acquired pneumonia as signature of severe COVID-19 infection: Lymphopenia in severe COVID-19 infection,10.1016/j.jinf.2020.02.029,,,,"In two recent articles from Huang C et al and Yang X in The Lancet,2,3 85% of critically ill patients with COVID-19 showed lymphopenia. The presence of lymphopenia as a signature of severe COVID-19 was confirmed by Wang D et al, who, in their study published in JAMA, reported that ICU patients suffering this infection had a median lymphocyte count of 800 cells/mm,3 with non survivors exhibiting persistent lymphopenia.4 ICU patients present also with high levels of plasma cytokines.2 The existence of hyper-cytokinemia in COVID-19 patients with lymphopenia could indicate a poor control of the pathogen, as showed in severe patients infected with the 2009 Pandemic Influenza virus. Interestingly, hypercytokinemia and lymphopenia were also evident in critical patients with Severe Acute Respiratory Syndrome due to the Coronavirus emerged in 2003 (SARS-CoV).5,6 These features (lymphopenia + hypercytokinemia) fit the characteristics of a particular immunological phenotype of community acquired pneumonia (CAP), lymphopenic CAP (L-CAP), which, as we recently demonstrated in an article published in the Journal of Infection, is associated with increased severity, mortality and a dysregulated immunological response.7 In their works, Yang X et al and Chen N et al propose a direct cytotoxic action of the virus to explain the low lymphocyte counts observed in the severe cases of COVID-19.3,8 But, in our opinion, host factors could also contribute to induce lymphopenia in these cases. Compared with those patients not requiring intensive care, COVID-19 patients admitted to the ICU are older and are more likely to have hypertension, diabetes, cardiovascular and cerebrovascular disease.4 Aging and chronic diseases induce chronic endothelial dysfunction. As we recently reviewed in J Clin Med, endothelial dysfunction induces disassembly of intercellular junctions, endothelial cell death and blood-tissue barrier disruption, along with enhanced leukocyte adhesion and extravasation, which could contribute to explain the lymphopenia observed in severe COVID-19 patients.9 Recent findings from our group have evidenced the interconnection between lymphopenia and endothelial dysfunction in patients with CAP and organ failure.10 Endothelial dysfunction induces also increased oxidative stress and systemic inflammation, glycocalyx degradation and shedding along with a pro-coagulant and anti-fibrinolytic state.9 In aged individuals with chronic diseases, these features could represent predisposing factors for presenting a severe respiratory failure following COVID-19 infection.",,"Bermejo-Martin, Jesús F.; Almansa, Raquel; Menéndez, Rosario; Mendez, Raúl; Kelvin, David J.; Torres, Antoni",Journal of Infection,2953538649,#3547,
,CZI,Public health might be endangered by possible prolonged discharge of SARS-CoV-2 in stool,10.1016/j.jinf.2020.02.031,,,,"The published data, which showed the COVID-19 patients with low digestive?manifestation, might be misleading. Case with negative URT test showed positive in?rectal scarab which challenge the isolation protocol.?As fomite transmission caused clusters of infection of SARS, adequate disinfection?operations should be adopted in SARS-CoV-2 outbreak.",,"He, Yu; Wang, Zhengli; Li, Fang; Shi, Yuan",Journal of Infection,3006332573,#3634,
,CZI,Traditional chinese medicine is a resource for drug discovery against 2019 novel coronavirus (SARS-CoV-2),10.1016/j.joim.2020.02.004,,,,,2020,"Ling, Chang-quan",Journal of Integrative Medicine,2958029267,#1288,
,CZI,Molecular immune pathogenesis and diagnosis of COVID-19,10.1016/j.jpha.2020.03.001,,,,"Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) in the twenty-first century. In this minireview, we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis, diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections, which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.",2020,"Li, Xiaowei; Geng, Manman; Peng, Yizhao; Meng, Liesu; Lu, Shemin",Journal of Pharmaceutical Analysis,1601033402,#4519,
,CZI,Quantitative computed tomography analysis for stratifying the severity of Coronavirus Disease 2019,10.1016/j.jpha.2020.03.004,,,,"Purpose To examine the feasibility of using a computer tool for stratifying the severity of Coronavirus Disease 2019 (COVID-19) based on computed tomography (CT) images. Materials and methods We retrospectively examined 44 confirmed COVID-19 cases. All cases were evaluated separately by radiologists (visually) and through an in-house computer software. The degree of lesions was visually scored by the radiologist, as follows, for each of the 5 lung lobes: 0, no lesion present; 1, <1/3 involvement; 2, >1/3 and < 2/3 involvement; and 3, >2/3 involvement. Lesion density was assessed based on the proportion of ground-glass opacity (GGO), consolidation and fibrosis of the lesions. The parameters obtained using the computer tool included lung volume (mL), lesion volume (mL), lesion percentage (%), and mean lesion density (HU) of the whole lung, right lung, left lung, and each lobe. The scores obtained by the radiologists and quantitative results generated by the computer software were tested for correlation. A Chi-square test was used to test the consistency of radiologist- and computer-derived lesion percentage in the right/left lung, upper/lower lobe, and each of the 5 lobes. Result The results showed a strong to moderate correlation between lesion percentage scores obtained by radiologists and the computer software (r ranged from 0.7679 to 0.8373, P < 0.05), and a moderate correlation between the proportion of GGO and mean lesion density (r = −0.5894, P < 0.05), and proportion of consolidation and mean lesion density (r = 0.6282, P < 0.05). Computer-aided quantification showed a statistical significant higher lesion percentage for lower lobes than that assessed by the radiologists (χ2 = 8.160, P = 0.004). Conclusions Our experiments demonstrated that the computer tool could reliably and accurately assess the severity and distribution of pneumonia on CT scans.",2020,"Shen, Cong; Yu, Nan; Cai, Shubo; Zhou, Jie; Sheng, Jiexin; Liu, Kang; Zhou, Heping; Guo, Youmin; Niu, Gang",Journal of Pharmaceutical Analysis,2970191042,#4449,
,CZI,Management strategy of Novel coronavirus pneumonia in burn and wound care ward,10.1016/j.jpra.2018.04.003,,,,"The prevention and control of novel coronavirus pneumonia (NCP) has already entered a key period . The patients treated in the burn and wound care ward are susceptible to viral infection because of disease, age and other factors, so it is very important to manage the burn and wound care ward during the prevention and control of NCP epidemic. In this paper, combining with the key clinical problems of prevention and control in hospital during the epidemic period of NCP infection, medical evidence, and clinical and management experience, the author formulates prevention and control management strategy of the author's unit in order to provide reference for prevention and control of burn and wound care ward.",2020,"LI, Ning; LIU, Ting Min; CHEN, Hua Ling; LIAO, Jian Mei",Chinese Journal of Burns,2808056403,#1965,
,CZI,Pulmonary pathology of early phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer,10.1016/j.jtho.2020.02.010,,,,"There is currently a lack of pathologic data on the novel coronavirus (SARS-CoV-2) pneumonia, or COVID-19, from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma were retrospectively found to have had COVID-19 at the time of surgery. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that, apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Since both patients did not exhibit symptoms of pneumonia at the time of surgery, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia.",2020,"Tian, Sufang; Hu, Weidong; Niu, Li; Liu, Huan; Xu, Haibo; Xiao, Shu-Yuan",Journal of Thoracic Oncology,3005943294,#2529,
,CZI,"Editorial: Coronaviruses: Facts, Myths and Hypotheses",10.1016/j.jtho.2020.02.024,,,,"Abstract 26 There is currently a lack of pathologic data on the novel coronavirus (SARS-CoV-2) 27 pneumonia, or COVID-19, from autopsy or biopsy. Two patients who recently 28 underwent lung lobectomies for adenocarcinoma were retrospectively found to have had 29 COVID-19 at the time of surgery. These two cases thus provide important first 30 opportunities to study the pathology of COVID-19. Pathologic examinations revealed 31 that, apart from the tumors, the lungs of both patients exhibited edema, proteinaceous 32 exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular 33 infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. 34 Since both patients did not exhibit symptoms of pneumonia at the time of surgery, these 35 changes likely represent an early phase of the lung pathology of COVID-19 pneumonia. 36 37 Key words: coronavirus; COVID-19 pneumonia, pathology; SARS-CoV-2 38 39 40",2020,"Carbone, Michele; Green, Joshua B.; Bucci, Enrico M.; Lednicky, John J.",Journal of Thoracic Oncology,2077304999,#5094,
,CZI,The Treatment and Outcome of a Lung Cancer Patient Infected with SARS-CoV-2,10.1016/j.jtho.2020.02.025,,,,,2020,"Zhang, Hongyan; Huang, Yihua; Xie, Conghua",Journal of Thoracic Oncology,2044076874,#4377,
,CZI,Suggestions for thoracic surgery clinical practice in non-epidemic area of coronavirus infected disease-19,10.1016/j.jvs.2010.08.027,,,,"In this paper, the mechanism of destroying human alveolar epithelial cells and pulmonary tissue by 2019 novel coronavirus (2019-nCoV) was discussed firstly. There may be multiple mechanisms including killing directly the target cells and hyperinflammatory responses. Secondly, the clinical features, CT imaging, short-term and long-term pulmonary function damage of the 2019 novel coronavirus pneumonia (COVID-19) was analyzed. Finally, some suggestions for thoracic surgery clinical practice in non-epidemic area during and after the epidemic of COVID-19 was provided, to help all the thoracic surgery patients receive active and effective treatment.",2020,"DAI, Fuqiang; TAN, Qunyou",Chinese Journal of Surgery,2113129487,#2314,
,CZI,The Novel Coronavirus 2019 Epidemic and Kidneys,10.1016/j.kint.2020.03.001,,,,,2020,"Naicker, Saraladevi; Yang, Chih-Wei; Hwang, Shang-Jyh; Liu, Bi-Cheng; Chen, Jiang-Hua; Jha, Vivekanand",Kidney International,3005643121,#4918,
,CZI,"Anti-HCV, nucleotide inhibitors, repurposing against COVID-19",10.1016/j.lfs.2020.117477,,,,"Aims A newly emerged Human Coronavirus (HCoV) is reported two months ago in Wuhan, China (COVID-19). Until today >2700 deaths from the 80,000 confirmed cases reported mainly in China and 40 other countries. Human to human transmission is confirmed for COVID-19 by China a month ago. Based on the World Health Organization (WHO) reports, SARS HCoV is responsible for >8000 cases with confirmed 774 deaths. Additionally, MERS HCoV is responsible for 858 deaths out of about 2500 reported cases. The current study aims to test anti-HCV drugs against COVID-19 RNA dependent RNA polymerase (RdRp). Materials and methods In this study, sequence analysis, modeling, and docking are used to build a model for Wuhan COVID-19 RdRp. Additionally, the newly emerged Wuhan HCoV RdRp model is targeted by anti-polymerase drugs, including the approved drugs Sofosbuvir and Ribavirin. Key findings The results suggest the effectiveness of Sofosbuvir, IDX-184, Ribavirin, and Remidisvir as potent drugs against the newly emerged HCoV disease. Significance The present study presents a perfect model for COVID-19 RdRp enabling its testing in silico against anti-polymerase drugs. Besides, the study presents some drugs that previously proved its efficiency against the newly emerged viral infection.",2020,"Elfiky, Abdo A.",Life Sciences,1174154477,#2799,
,CZI,Guide to Understanding the 2019 Novel Coronavirus,10.1016/j.mayocp.2020.02.003,,,,,2020,"Shah, Aditya; Kashyap, Rahul; Tosh, Pritish; Sampathkumar, Priya; O’Horo, John C.",Mayo Clinic Proceedings,3003790823,#2933,
,CZI,"One world, one health: The novel coronavirus COVID-19 epidemic",10.1016/j.medcli.2020.02.002,,32093921,,,2020,"Trilla, Antoni",Med Clin (Barc),3005802710,#1924,
,CZI,Novel coronavirus: From discovery to clinical diagnostics,10.1016/j.meegid.2020.104211,,,,"A novel coronavirus designated as 2019-nCoV first appeared in Wuhan, China in late December 2019. Dozens of people died in China, and thousands of people infected as 2019-nCoV continues to spread around the world. We have described the discovery, emergence, genomic characteristics, and clinical diagnostics of 2019-nCoV.",2020,"Phan, Tung","Infection, Genetics and Evolution",3004202398,#108,
,CZI,Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event,10.1016/j.meegid.2020.104212,,,,"Background A novel coronavirus (2019-nCoV) associated with human to human transmission and severe human infection has been recently reported from the city of Wuhan in China. Our objectives were to characterize the genetic relationships of the 2019-nCoV and to search for putative recombination within the subgenus of sarbecovirus. Methods Putative recombination was investigated by RDP4 and Simplot v3.5.1 and discordant phylogenetic clustering in individual genomic fragments was confirmed by phylogenetic analysis using maximum likelihood and Bayesian methods. Results Our analysis suggests that the 2019-nCoV although closely related to BatCoV RaTG13 sequence throughout the genome (sequence similarity 96.3%), shows discordant clustering with the Bat_SARS-like coronavirus sequences. Specifically, in the 5′-part spanning the first 11,498 nucleotides and the last 3′-part spanning 24,341–30,696 positions, 2019-nCoV and RaTG13 formed a single cluster with Bat_SARS-like coronavirus sequences, whereas in the middle region spanning the 3′-end of ORF1a, the ORF1b and almost half of the spike regions, 2019-nCoV and RaTG13 grouped in a separate distant lineage within the sarbecovirus branch. Conclusions The levels of genetic similarity between the 2019-nCoV and RaTG13 suggest that the latter does not provide the exact variant that caused the outbreak in humans, but the hypothesis that 2019-nCoV has originated from bats is very likely. We show evidence that the novel coronavirus (2019-nCov) is not-mosaic consisting in almost half of its genome of a distinct lineage within the betacoronavirus. These genomic features and their potential association with virus characteristics and virulence in humans need further attention.",2020,"Paraskevis, D.; Kostaki, E.G.; Magiorkinis, G.; Panayiotakopoulos, G.; Sourvinos, G.; Tsiodras, S.","Infection, Genetics and Evolution",3003223635,#41,
,CZI,Genetic diversity and evolution of SARS-CoV-2,10.1016/j.meegid.2020.104260,,,,COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and rapid evolution of this novel coronavirus.,2020,"Phan, Tung","Infection, Genetics and Evolution",3006448444,#1522,
,CZI,"Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China",10.1016/j.micinf.2020.01.003,,,,"On 10 January 2020, a new coronavirus causing a pneumonia outbreak in Wuhan City in central China was denoted as 2019-nCoV by the World Health Organization (WHO). As of 24 January 2020, there were 887 confirmed cases of 2019-nCoV infection, including 26 deaths, reported in China and other countries. Therefore, combating this new virus and stopping the epidemic is a matter of urgency. Here, we focus on advances in research and development of fast diagnosis methods, as well as potential prophylactics and therapeutics to prevent or treat 2019-nCoV infection.",2020,"Yu, Fei; Du, Lanying; Ojcius, David M.; Pan, Chungen; Jiang, Shibo",Microbes and Infection,3003191692,#118,
,CZI,Mysterious infections in China: Novel coronavirus identified as cause of pneumonia,10.1016/j.micinf.2020.01.003,,,,,2020,,Deutsche Apotheker Zeitung,3003191692,#116,
,CZI,The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future,10.1016/j.micinf.2020.02.002,,,,"At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.",2020,"Li, Jin-Yan; You, Zhi; Wang, Qiong; Zhou, Zhi-Jian; Qiu, Ye; Luo, Rui; Ge, Xing-Yi",Microbes and Infection,3004668429,#1384,
,CZI,Lessons learned from the 2019-nCoV epidemic on prevention of future infectious diseases,10.1016/j.micinf.2020.02.004,,,,"Only a month after the outbreak of pneumonia caused by 2019-nCoV, more than forty-thousand people were infected. This put enormous pressure on the Chinese government, medical healthcare provider, and the general public, but also made the international community deeply nervous. On the 25th day after the outbreak, the Chinese government implemented strict traffic restrictions on the area where the 2019-nCoV had originated—Hubei province, whose capital city is Wuhan. Ten days later, the rate of increase of cases in Hubei showed a significant difference (p = 0.0001) compared with the total rate of increase in other provinces of China. These preliminary data suggest the effectiveness of a traffic restriction policy for this pandemic thus far. At the same time, solid financial support and improved research ability, along with network communication technology, also greatly facilitated the application of epidemic prevention measures. These measures were motivated by the need to provide effective treatment of patients, and involved consultation with three major groups in policy formulation—public health experts, the government, and the general public. It was also aided by media and information technology, as well as international cooperation. This experience will provide China and other countries with valuable lessons for quickly coordinating and coping with future public health emergencies.",2020,"Pan, Xingchen; Ojcius, David M.; Gao, Tianyue; Li, Zhongsheng; Pan, Chunhua; Pan, Chungen",Microbes and Infection,2321034157,#1367,
,CZI,Is COVID-19 Receiving ADE From Other Coronaviruses?,10.1016/j.micinf.2020.02.006,,,,"One of the most perplexing questions regarding the current COVID-19 coronavirus epidemic is the discrepancy between the severity of cases observed in the Hubei province of China and those occurring elsewhere in the world. One possible answer is antibody dependent enhancement (ADE) of SARS-CoV-2 due to prior exposure to other coronaviruses. ADE modulates the immune response and can elicit sustained inflammation, lymphopenia, and/or cytokine storm, one or all of which have been documented in severe cases and deaths. ADE also requires prior exposure to similar antigenic epitopes, presumably circulating in local viruses, making it a possible explanation for the observed geographic limitation of severe cases and deaths.",2020,"Tetro, Jason A.",Microbes and Infection,3006338236,#1484,
,CZI,Internatioanl News Letter - April 2020,10.1016/j.midw.2020.102668,,,,,2020,"Duff, Elizabeth",Midwifery,2990427063,#4644,
,CZI,Effect of TLR agonist on infections bronchitis virus replication and cytokine expression in embryonated chicken eggs,10.1016/j.molimm.2020.02.001,,,,"Avian infectious bronchitis (IB) is an acute, highly infectious and contagious viral disease of chickens caused by avian infectious bronchitis virus (IBV) belonging to the genus Coronavirus and family Coronaviridae. It can affect all age groups of birds. The toll-like receptors (TLRs) are a major class of innate immune pattern recognition receptors that have a key role in immune response and defense against various infections.The TLRs are essential for initiation of innate immune responses and in the development of adaptive immune responses. An in ovo model was employed to study the antiviral activity of TLR ligands (Pam3CSK4, LPS and CpG ODN) on replication of IBV. It was hypothesized that optimum dose and specific timing of TLR ligands may reduce viral load of IBV in specific pathogen free (SPF) embryonated chicken eggs (ECEs). Further, the mechanism involved in the TLR-mediated antiviral response in chorioallantoic membrane (CAM) of ECEs was investigated. The ECEs of 9–11 days old were treated with different doses (high, intermediate and low) of TLR-2 (Pam3CSK4), TLR-4 (LPS) and TLR-21 (CpG ODN) ligands. In addition, to know the timing of TLR ligand treatment, six time intervals were analyzed viz. 36, 24 and 12 h prior to infection, time of infection (co-administration of TLR ligands and avian IBV) and 12 and 24 h post-IBV infection. For studying the relative expression of immuno-stimulatory genes (IFN-α, IFN-β, IFN-γ, IL-1β, iNOS and OAS) in CAM, TLR ligands were administered through intra-allantoicroute and CAM were collected at 4, 8 and 16 h post treatment. The results demonstrated that intermediate dose of all the three TLR ligands significantly reduced virus titers and used in the present study. However, the LPS reduced virus titer pre- and post-IBV infection but Pam3CSK4 and CpG ODN reduced only pre-IBV infection. Further analysis showed that TLR ligands induced IFN-γ, IL-1β and IFN stimulated genes viz. iNOS and OAS genes in CAM. The present study pointed towards the novel opportunities for rational design of LPS as immuno-stimulatory agent in chickens with reference to IBV. It may be speculated that in ovo administration of these TLR ligands may enhance resistance against viral infection in neonatal chicken and may contribute towards the development of more effective and safer vaccines including in ovo vaccines.",2020,"Sharma, Bal Krishan; Kakker, Naresh Kumar; Bhadouriya, Sakshi; Chhabra, Rajesh",Molecular Immunology,3006185830,#2404,
,CZI,"Novel Viruses, Zoonotic Infections, and Travel Health",10.1016/j.nwh.2020.02.002,,,,,2020,"Brucker, Mary C.",Nursing for Women's Health,1603291205,#1687,
,CZI,Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus,10.1016/j.pcad.2020.02.007,,,,,2020,"McCarty, Mark F.; DiNicolantonio, James J.",Progress in Cardiovascular Diseases,3005568099,#824,
,CZI,Traditional Chinese Medicine for COVID-19 Treatment,10.1016/j.phrs.2020.104743,,,,,2020,"Ren, Jun-ling; Zhang, Ai-Hua; Wang, Xi-Jun",Pharmacological Research,2998439854,#4461,
,CZI,"In bid to rapidly expand coronavirus testing, U.S. agency abruptly changes rules | Science | AAAS",10.1016/j.prevetmed.2015.10.018,,,,"The Food and Drug Administration (FDA) today recommended a dramatic shift in how it implements regulations that control whether laboratories can use diagnostic kits created in-house to test for infections of coronavirus-2019 (COVID-19). “We issued a policy this morning that allows us to have a lot of flexibility around the development of diagnostic tests,” said FDA Commissioner Stephen Hahn at a White House briefing with President Donald Trump this afternoon. “We expect this policy to have a significant impact.” The change could greatly expand the number of laboratories able to do coronavirus testing. The U.S. government has come under severe criticism for not providing nearly enough tests needed to understand the extent of spread in the population. A test kit produced and distributed by the U.S. Centers for Disease Control and Prevention (CDC) was shelved after state and local lab trying it out discovered that it contained a faulty reagent. As a result, many labs that have the capability to test themselves have not been allowed to do so. The new recommendations focus on “high-complexity testing laboratories” that are certified under federal rules known as Clinical Laboratory Improvement Amendments. This group of facilities includes many hospital labs, like the one that epidemiologist Michael Mina works at Brigham and Women’s Hospital in Boston. “Essentially it’s opening up a clear and concise avenue for labs like the one at Brigham and Women’s,” says Mina. “It’s what I’ve been advocating for a month now.”",2020,"Cohen, Jon",Science Magazine,1927230155,#2778,
,CZI,Psychological crisis interventions in Sichuan Province during the 2019 novel coronavirus outbreak,10.1016/j.psychres.2020.112895,,,,,2020,"Zhou, Xiaobo",Psychiatry Research,3006425298,#3033,
,CZI,The psychiatric impact of the novel coronavirus outbreak,10.1016/j.psychres.2020.112902,,,,,2020,"Carvalho, Poliana Moreira de Medeiros; Moreira, Marcial Moreno; de Oliveira, Matheus Nogueira Arcanjo; Landim, José Marcondes Macedo; Neto, Modesto Leite Rolim",Psychiatry Research,3004810054,#2749,
,CZI,Psychological crisis intervention during the outbreak period of new coronavirus pneumonia from experience in Shanghai,10.1016/j.psychres.2020.112903,,,,"Since the middle of December 2019, human-to-human transmission of novel coronavirus pneumonia (NCP) has occurred among close contacts. At the same time, greater attention should be paid to psychological crisis intervention (PCI) among affected populations, for the timely prevention of inestimable damage from a secondary psychological crisis. PCI has been initiated via remote (telephone and internet) and onsite medical services to help medical workers, patients, and others affected to overcome any psychological difficulties. This paper outlines experiences based on the work of the Shanghai Medical Team.",2020,"Jiang, Xixi; Deng, Lili; Zhu, Yuncheng; Ji, Haifeng; Tao, Lily; Liu, Li; Yang, Daoliang; Ji, Weidong",Psychiatry Research,2615103260,#2848,
,CZI,Wuhan novel coronavirus (COVID-19): why global control is challenging?,10.1016/j.puhe.2020.02.001,,,,,2020,"Lee, A.",Public Health,3006113744,#2609,
,CZI,And now for something completely different: from 2019-nCoV and COVID-19 to 2020-nMan,10.1016/j.pulmoe.2020.02.010,,,,"Infectious diseases have accompanied mankind since the beginning of humanity and have had a profound impact on the history and development of humanity and civilisation. This is natural if we are aware that microorganisms represent the majority of the biomass on planet Earth, and that there are more microorganisms, specifically bacteria, in the human body than there are cells. To be more precise, about 1012 human cells for every 1013 bacteria, as an adaptive advantage of the replication of bacteria that occurs every 20–40 min, as against tens of years in the human species. Infectious diseases, in particular pandemics and local epidemics, have influenced the course of wars, all descendants, including those of rulers, and the fate of peoples and nations.1 By way of example, we should remember the importance of malaria in the fall of the Roman Empire, the Black Death in the 14th century which killed nearly a third of the world’s population, and the impact of the “Spanish” flu pandemic of 1918–19 in Portugal, which in a few months decimated 1% of the Portuguese population and reduced average life expectancy to 20 years and, more recently, smallpox, declared eradicated by the World Health Organization (WHO) in 1980 as a result of vaccination,2 and with an estimated mortality in the 20th century of between 300 and 500 million people.3 In light of this impact, it is legitimate to consider infections one of the main modellers of mankind and of present and future generations, as well as generations of the descendants of survivors. We have also been major challengers of infectious diseases in the 21st century. Most notably in 2009 and 2010, when the 2009 influenza pandemic caused by the A (H1N1) subtype strain occurred, which originated in Mexico, with a virulence rate of 5–10% of the world’s population, and an estimated mortality of 300,000 people. In Portugal there were 124 deaths, with an average age of 47.6 years, corresponding to a crude death rate of 1.17 per 100,000 inhabitants.4 However, it is in the first decades of the 21st century when the number of outstanding cases corresponded entirely to Coronaviridae of the family Coronaviridae, from the Latin corona, given its crown shape under electronic microscope. These viruses belong to a large family of RNA viruses, with abundant expression in the animal kingdom, particularly bats, and also other mammals, birds and reptiles. The first outbreak of coronavirus disease was the result of a cross-species barrier jump, originating in bats, and probably the musk cat as a secondary host, which began on November 16, 2002 and was named SARS-CoV (Severe Acute Respiratory Syndrome - CoronaVirus) in Guangdong Province, of the People’s Republic of China, and extended to 17 countries, including Canada, the United States of America (USA), Australia, Germany, France, Sweden, the United Kingdom and Spain. The WHO declared an end to the risk of new cases on 19 May 2004, with an estimated total of approximately 8096 cases and at least 774 deaths.5",2020,"Froes, F.",Pulmonology,3006602665,#4676,
,CZI,High resolution CT features of novel coronavirus pneumonia in children,10.1016/j.radcr.2019.03.016,,,,"Objective To investigate the high resolution CT (HRCT) features of novel coronavirus pneumonia (NCP) in children . Methods A retrospective analysis was performed on the chest HRCT findings of 22 children diagnosed with 2019-nCov pneumonia by clinical and nucleic acid testing in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 25, 2020 to February 5, 2020. There were 12 boys and 10 girls, aged from 2 months to 14 years old, with a median age of 4 years, and 14 patients were under 5 years old. The characteristics of lung lesions on HRCT imaging such as distribution, shape, density, etc. and whether there were hilar and mediastinal lymph node enlargement and pleural changes were observed by 2 radiologists. Results In all of the 22 patients, 3 patients (3/22) had normal chest CT, and 19 patients (19/22) had infiltrated lesions in lung. Among them, 7 patients had unilateral lung involvement, 12 patients had bilateral involvement. The HRCT manifestations were as follows. Six patients showed ground glass shadow, including 4 cases showed light ground glass shadow and 2 had typical crazy paving sign. Four patients showed lung consolidation, with localized strip shadow and patchy high-density shadow. Six patients showed patchy lesions with surrounding ground glass shadow, including 1 case with white lung in the right. The bronchopneumonia-like changes in 3 cases, showed scattered spot-like or patchy uneven high-density shadows. The lesions in the lower lobe were more serious than those in the upper lobe, and the lesions in the lateroposterior zone of the lung were more common than those in the apical and central area of the lung. No enlarged lymph nodes and pleural effusion were seen in all patients, and 1 case had thickened interlobar pleura. Conclusions The HRCT manifestations of NCP in children are diversified, comprehensive judgments need to be made in combination with epidemiological data, clinical manifestations, and laboratory tests, but the chest HRCT can be used as an important basis for early clinical diagnosis and prevention and control interventions.",2020,"MA, Huijing; SHAO, Jianbo; WANG, Yongjiao; ZHAI, Aiguo; ZHENG, Nannan; LI, Quan; LIU, Yan",Chinese Journal of Radiology,2934726322,#2174,
,CZI,High resolution CT findings and clinical features of novel coronavirus pneumonia in Guangzhou,10.1016/j.radcr.2019.03.016,,,,"To investigate the initial HRCT manifestations and clinical features of imported novel coronavirus pneumonia (NCP) in Guangzhou. Methods. A retrospective analysis of 91 NCP patients admitted to the Guangzhou Eighth People’s Hospital from January 22 to 30, 2020 was performed including 39 males and 52 females, with a median age of 50 (33-62) years, then their clinical features and HRCT characteristics were analyzed. Results. The main clinical presentations included fever in 70 cases and cough in 57 cases(mainly dry coughin39 cases). The first time HRCT showed that 24 cases with NCP were normal, however other 67 cases were abnormal. The ground glass opacity in the lung on HRCT was found in 65 cases, including 64 cases with dilated blood vessel crossing the lesion, 50 cases with thickened adjacent pleura, and 47 cases with thickening of interstitial septum. The patchy opacity was seen in 42 cases, and no enlarged lymph nodes were observed in all patients. As for the lesion distribution, there were two cases with bilateral diffuse changes, 57 cases with multiple lesions, 8 cases with the lesion in only one lobe. The lesions were mainly located under the pleura area in 46 cases, including 39 cases in the lower lobe and other 7 cases in the upper lobe. And there were 13 cases without characteristic distribution in the lung. Conclusions. The initial images of NCP in Guangzhou mainly showed multiple ground glass opacity, which were mostly seen in the subpleural and lower lung fields, most of them with thickened pulmonary interstitium. Guangzhou has a higher proportion of NCP patients with mild and general patients, and some confirmed patients show negative HRCT for the first time. Patients without HRCT changes should be reviewed in a timely manner.",2020,"Yu, Chengcheng; Qu, Jing; Zhang, Songfeng; Jiang, Songfeng; Chen, Bihua; Guan, Wanhua; Gan, Qingxin; Huang, Deyang; Ling, Zhoukun; Jiang, Rui; Lin, Lin; Liu, Jinxin",Chinese Journal of Radiology,2934726322,#1898,
,CZI,A Novel Coronavirus Emerges,10.1016/j.rce.2020.01.001,,32063263,,,2020,"Ena, J.; Wenzel, R. P.",Rev Clin Esp,3006338959,#1146,
,CZI,Key points of serious adverse eventand protection of patients in ophthalmic clinical trials during novel coronavirus pneumonia outbreak,10.1016/j.rmed.2019.02.021,,,,"The prevention and control of novel coronavirus pneumonia is the most priority recently, and various measures during the prevention and control period will have varying degrees of impact on the implement of clinical trials. However, various examinations in ophthalmological clinical trials need close contact between operators and patients, which put us at risk of cross-infection. This paper indicated some suggestions based on the criteria of clinical trials under major public health emergencies, the management of clinical trials during epidemic period including the follow-up of subjects, the treatment of epidemic serious adverse event (SAE) and the management requirements of co-sponsors, as well as the requirements and management principles for environment, subjects, examiners and inspection equipment in the process of ophthalmic clinical trials. It may be helpful to the ophthalmic clinical trial researchers and subjects during the period of novel coronavirus infection.",2020,"ZHANG, Peng; LU, Yingyi; SONG, Shuang; YU, Xiaobing; DAI, Hong",Chinese Journal of Experimental Ophthalmology,2921734897,#2062,
,CZI,Community pharmacist in public health emergencies: Quick to action against the coronavirus 2019-nCoV outbreak,10.1016/j.sapharm.2020.02.003,,,,"The 2019-nCoV infection that is caused by a novel strain of coronavirus was first detected in China in the end of December 2019 and declared a public health emergency of international concern by the World Health Organization on January 30, 2020. Community pharmacists in one of the first areas that had confirmed cases of the viral infection, Macau, joined the collaborative force in supporting the local health emergency preparedness and response arrangements. This paper aimed to improve the understanding of community pharmacists’ role in case of 2019-CoV outbreak based on the practical experiences in consultation with the recommendations made by the International Pharmaceutical Federation on the Coronavirus 2019-nCoV outbreak.",2020,"Lam Ung, Carolina Oi",Research in Social and Administrative Pharmacy,3005668029,#762,
,CZI,A data driven time-dependent transmission rate for tracking an epidemic: a case study of 2019-nCoV,10.1016/j.scib.2020.02.005,,,,,2020,"Huang, Norden E.; Qiao, Fangli",Science Bulletin,3005064183,#492,
,CZI,The inflection point about COVID-19 may have passed,10.1016/j.scib.2020.02.025,,,,,2020,"Gu, Chaolin; Zhu, Jie; Sun, Yifei; Zhou, Kai; Gu, Jiang",Science Bulletin,1969146377,#3170,
,CZI,A disconnected policy network: The UK's response to the Sierra Leone Ebola epidemic,10.1016/j.socscimed.2020.112851,,,,"This paper investigates whether the inclusion of social scientists in the UK policy network that responded to the Ebola crisis in Sierra Leone (2013–16) was a transformational moment in the use of interdisciplinary research. In contrast to the existing literature, that relies heavily on qualitative accounts of the epidemic and ethnography, this study tests the dynamics of the connections between critical actors with quantitative network analysis. This novel approach explores how individuals are embedded in social relationships and how this may affect the production and use of evidence. The meso-level analysis, conducted between March and June 2019, is based on the traces of individuals' engagement found in secondary sources. Source material includes policy and strategy documents, committee papers, meeting minutes and personal correspondence. Social network analysis software, UCINet, was used to analyse the data and Netdraw for the visualisation of the network. Far from being one cohesive community of experts and government officials, the network of 134 people was weakly held together by a handful of super-connectors. Social scientists’ poor connections to the government embedded biomedical community may explain why they were most successful when they framed their expertise in terms of widely accepted concepts. The whole network was geographically and racially almost entirely isolated from those affected by or directly responding to the crisis in West Africa. Nonetheless, the case was made for interdisciplinarity and the value of social science in emergency preparedness and response. The challenge now is moving from the rhetoric to action on complex infectious disease outbreaks in ways that value all perspectives equally.",2020,"Georgalakis, James",Social Science & Medicine,3006112521,#817,
,CZI,EuNPs-mAb fluorescent probe based immunochromatographic strip for rapid and sensitive detection of porcine epidemic diarrhea virus,10.1016/j.talanta.2020.120865,,,,"Porcine epidemic diarrhea (PED), induced by porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, vomiting, dehydration and high mortality in neonatal piglets, resulting in significant economic losses in the pig industries. In this study, an immunochromatographic assay (ICA) based on a EuNPs-mAb fluorescent probe was developed and optimized for rapid detection of PEDV. The limit of detection (LOD) of the ICA was 0.218 μg/mL (2.725 × 103 TCID50/mL) and its linear detection range was 0.03125–8 μg/mL (3.91 × 102-105 TCID50/mL). The ICA was also validated for the detection of PEDV in swine stool samples. 60 swine stool samples from southern China were analyzed by the ICA and RT-PCR, and the results showed that the coincidence rate of the ICA to RT-PCR was 86.67%, which was significantly higher than that of AuNPs based ICA. The ICA is sensitive and specific and can achieve on-site rapid detection of swine stool samples. Therefore, the ICA has a great potential for PED diagnosis and prevention.",2020,"Xu, Fei; Jin, Zhiyuan; Zou, Siyi; Chen, Chaoqun; Song, Qifang; Deng, Shengchao; Xiao, Wei; Zhang, Xiaoli; Jia, Aiqing; Tang, Yong",Talanta,2084580389,#2107,
,CZI,Unveiling the Origin and Transmission of 2019-nCoV,10.1016/j.tim.2020.02.001,,,,"A novel coronavirus has caused thousands of human infections in China since December 2019, raising a global public health concern. Recent studies (Huang et al., Chan et al., and Zhou et al.) have provided timely insights into its origin and ability to spread among humans, informing infection prevention and control practices.",,"Xu, Yifei",Trends in Microbiology,2747380789,#1734,
,CZI,"SARS-CoV, MERS-CoV and now the 2019-novel CoV: Have we investigated enough about coronaviruses? – A bibliometric analysis",10.1016/j.tmaid.2020.101566,,,,,2020,"Bonilla-Aldana, D. Katterine; Quintero-Rada, Keidenis; Montoya-Posada, Juan Pablo; Ramírez, Sebastian; Paniz-Mondolfi, Alberto; Rabaan, Ali; Sah, Ranjit; Rodríguez-Morales, Alfonso J.",Travel Medicine and Infectious Disease,,#64,
,CZI,"The next big threat to global health? 2019 novel coronavirus (2019-nCoV): What advice can we give to travellers? – Interim recommendations January 2020, from the Latin-American society for Travel Medicine (SLAMVI)",10.1016/j.tmaid.2020.101567,,,,,2020,"Biscayart, Cristian; Angeleri, Patricia; Lloveras, Susana; Chaves, Tânia do Socorro Souza; Schlagenhauf, Patricia; Rodríguez-Morales, Alfonso J.",Travel Medicine and Infectious Disease,,#67,
,CZI,The association between domestic train transportation and novel coronavirus (2019-nCoV) outbreak in China from 2019 to 2020: A data-driven correlational report,10.1016/j.tmaid.2020.101568,,32006656,,,2020,"Zhao, Shi; Zhuang, Zian; Ran, Jinjun; Lin, Jiaer; Yang, Guangpu; Yang, Lin; He, Daihai",Travel medicine and infectious disease,3003807992,#4317,
,CZI,Outbreak of novel Corona Virus (2019-nCoV); implications for travelers to Pakistan?,10.1016/j.tmaid.2020.101571,,,,,2020,"Rahman Qureshi, Ubaid Ur; Saleem, Sadia; Khan, Aisha; Afzal, Muhammad Sohail; Ali, Muhammad Shahzad; Ahmed, Haroon",Travel Medicine and Infectious Disease,3005325774,#218,
,CZI,"What goes on board aircraft? Passengers include Aedes, Anopheles, 2019-nCoV, dengue, Salmonella, Zika, et al",10.1016/j.tmaid.2020.101572,,,,,2020,"Wilson, Mary E.",Travel Medicine and Infectious Disease,3004776013,#365,
,CZI,"Maps, masks and media – Traveller and practitioner resources for 2019 novel coronavirus (2019-nCoV) acute respiratory virus",10.1016/j.tmaid.2020.101574,,,,,2020,"Chiodini, Jane",Travel Medicine and Infectious Disease,,#490,
,CZI,"Coronavirus infections reported by ProMED, February 2000–January 2020",10.1016/j.tmaid.2020.101575,,,,"Introduction Sources describing the global burden of emerging diseases accurately are still limited. We reviewed coronavirus infections reported by ProMED and assessed the reliability of the data retrieved compared to published reports. We evaluated the effectiveness of ProMED as a source of epidemiological data on coronavirus. Methods Using the keyword “coronavirus” in the ProMED search engine, we reviewed all the information from the reports and collected data using a structured form, including year, country, gender, occupation, the number of infected individuals, and the number of fatal cases. Results We identified 109 entries reported between February 29, 2000 and January 22, 2020. A total of 966 cases were reported, with death reported in 188 cases, suggesting an overall case fatality rate (CFR) of 19.5%. Of 70 cases for which the gender was reported, 47 (67.1%) were male. Most of the cases were reported from China, the United Arab Emirates, and Saudi Arabia, with reports from other countries, including imported cases in Europe and North America. Conclusions Internet-based reporting systems such as ProMED are useful to gather information and synthesize knowledge on emerging infections. Although certain areas need to be improved, ProMED provided useful information about coronaviruses especially during outbreaks.",2020,"Bonilla-Aldana, D. Katterine; Holguin-Rivera, Yeimer; Cortes-Bonilla, Isabella; Cardona-Trujillo, María C.; García-Barco, Alejandra; Bedoya-Arias, Hugo A.; Rabaan, Ali A.; Sah, Ranjit; Rodriguez-Morales, Alfonso J.",Travel Medicine and Infectious Disease,,#424,
,CZI,Coronavirus 2019-nCoV: Is the genie already out of the bottle?,10.1016/j.tmaid.2020.101577,,,,,2020,"Hanscheid, Thomas; Valadas, Emília; Grobusch, Martin P.",Travel Medicine and Infectious Disease,3004801973,#489,
,CZI,Going global – Travel and the 2019 novel coronavirus,10.1016/j.tmaid.2020.101578,,,,,2020,"Rodríguez-Morales, Alfonso J.; MacGregor, Kirsten; Kanagarajah, Sanch; Patel, Dipti; Schlagenhauf, Patricia",Travel Medicine and Infectious Disease,,#487,
,CZI,The COVID-19 outbreak and implications for the Tokyo 2020 Summer Olympic Games,10.1016/j.tmaid.2020.101604,,,,,2020,"Gallego, Viviana; Nishiura, Hiroshi; Sah, Ranjit; Rodriguez-Morales, Alfonso J.",Travel Medicine and Infectious Disease,2891291435,#2288,
,CZI,"Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis",10.1016/j.tmaid.2020.101606,,,,,2020,"Huang, Yihui; Tu, Mengqi; Wang, Shipei; Chen, Sichao; Zhou, Wei; Chen, Danyang; Zhou, Lin; Wang, Min; Zhao, Yan; Zeng, Wen; Huang, Qi; Xu, Hai'bo; Liu, Zeming; Guo, Liang",Travel Medicine and Infectious Disease,2897243354,#2839,
,CZI,COVID-19: Zoonotic aspects,10.1016/j.tmaid.2020.101607,,,,,2020,"Ahmad, Tauseef; Khan, Muhammad; Haroon; Musa, Taha Hussein; Nasir, Saima; Hui, Jin; Bonilla-Aldana, D. Katterine; Rodriguez-Morales, Alfonso J.",Travel Medicine and Infectious Disease,2921548154,#2451,
,CZI,Asymptomatic coronavirus infection: MERS-CoV and SARS-CoV-2 (COVID-19),10.1016/j.tmaid.2020.101608,,,,,2020,"Al-Tawfiq, Jaffar A.",Travel Medicine and Infectious Disease,2921429935,#2444,
,CZI,COVID-19 in Latin America: The implications of the first confirmed case in Brazil,10.1016/j.tmaid.2020.101613,,32126292,,,2020,"Rodriguez-Morales, Alfonso J.; Gallego, Viviana; Escalera-Antezana, Juan Pablo; Mendez, Claudio A.; Zambrano, Lysien I.; Franco-Paredes, Carlos; Suárez, Jose A.; Rodriguez-Enciso, Hernan D.; Balbin-Ramon, Graciela Josefina; Savio-Larriera, Eduardo; Risquez, Alejandro; Cimerman, Sergio",Travel Med Infect Dis,2026978646,#3315,
,CZI,Remdesivir as a possible therapeutic option for the COVID-19,10.1016/j.tmaid.2020.101615,,,,,2020,"Al-Tawfiq, Jaffar A.; Al-Homoud, Ali H.; Memish, Ziad A.",Travel Medicine and Infectious Disease,2985999596,#4636,
,CZI,Positive result of Sars-Cov-2 in sputum from a cured patient with COVID-19,10.1016/J.TMAID.2020.101619,,,,"ince December 2019, an outbreak of the novel coronavirus (SARS-CoV-2) infection has spread rapidly in Wuhan, China [1]1. Over a month since the outbreak, more than 13,000 patients with COVID-19 have be cured and discharged from hospital until now. For the clinical cure criteria in China, twice successive negative results of Sars-Cov-2 nucleic acid detection are the important index, in addition to normal body temperature for 3 days as well as obvious improvement in respiratory symptoms and CT scan [2]. In the present work, we reported that Sars-Cov-2 nucleic acid was still detectable in sputum obtained by nebulization from a cured patient. On January 22, a 49-year-old man presented himself with fever for 4 days to a clinic. Throat swab detection was positive for SARS-CoV-2 nucleic acid by real-time RT-PCR. Subsequently, the patient was diagnosed with COVID-19 according to the diagnostic criteria [2] as follows (1): the positive result of SARS-CoV-2 nucleic acid detection (2); a history of short stay in Wuhan within 14 days; and (3) symptoms of fever, and multiple patchy areas of ground-glass opacity on CT scan. After the active treatment, the patient recovered from fever and other respiratory symptoms on February 4. On February 9 and February 10, the SARS-CoV-2 nucleic acid detection was successively negative in his throat swab samples. The CT scan result showed that the inflammation was significantly decreased in both lungs. Both the results of SARS-CoV-2 nucleic acid detection and CT scans indicated a recovery trend, and the patient was ready for discharge. On February 13, the throat swab and sputum by nebulization were collected before the patient was discharged. Notably, SARS-CoV-2 nucleic acid was still detected in sputum from the patient although negative result of throat swab detection.",2020,"Qu, Ye-Min; Cong, Hai-Yan",Travel Medicine and Infectious Disease,3006645647,#4977,
,CZI,Coronavirus Disease 2019: Coronaviruses and Blood Safety,10.1016/j.tmrv.2020.02.003,,,,"With the outbreak of unknown pneumonia in Wuhan, China in December 2019, a new coronavirus, Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) aroused the attention of the entire world. The current outbreak of infections with SARS-CoV-2 is termed Corona Virus Disease- 2019 (COVID-19). The World Health Organization (WHO) declared COVID-19 in China as a Public Health Emergency of International Concern (PHEIC). Two other corona virus infections-- SARS in 2002–2003 and Middle East Respiratory Syndrome (MERS) in 2012-- both caused severe respiratory syndrome in humans. All three of these emerging infectious diseases leading to a global spread are caused by beta-coronaviruses. Although coronaviruses usually infect the upper or lower respiratory tract, viral shedding in plasma or serum is common. Therefore, there is still a theoretical risk of transmission of coronaviruses through the transfusion of labile blood products. Because more and more asymptomatic infections are being found among COVID-19 cases, considerations of blood safety and coronaviruses have arisen especially in endemic areas. In this review, we detail current evidence and understanding of the transmission of SARS-CoV, MERS-CoV and SARS-CoV-2 through blood products as of February 10, 2020 and also discuss pathogen inactivation methods on coronaviruses.",2020,"Chang, Le; Yan, Ying; Wang, Lunan",Transfusion Medicine Reviews,2892593968,#1681,
,CZI,COVID-19 and blood safety: help with a dilemma,10.1016/j.tmrv.2020.02.004,,,,,2020,"Dodd, Roger Y.; Stramer, Susan L.",Transfusion Medicine Reviews,2785996973,#1998,
,CZI,"Another coronavirus, another epidemic, another warning",10.1016/j.vaccine.2020.02.039,,,,,2020,"Poland, Gregory A.",Vaccine,2302832176,#1361,
,CZI,Efficacy of orally administered porcine epidemic diarrhea vaccine-loaded hydroxypropyl methylcellulose phthalate microspheres and RANKL-secreting L. lactis,10.1016/j.vetmic.2020.108604,,,,"Here, we examined the efficacy of are combinant subunit antigen-based oral vaccine for preventing porcine epidemic diarrhea virus (PEDV). First, we generated a soluble recombinant partial spike S1 protein (aP2) from PEDV in E. coli and then evaluated the utility of aP2 subunit vaccine-loaded hydroxypropyl methylcellulose phthalate microspheres (HPMCP) and RANKL-secreting L. lactis (LLRANKL) as a candidate oral vaccine in pregnant sows. Pregnant sows were vaccinated twice (with a 2 week interval between doses) at 4 weeks before farrowing. Titers of virus-specific IgA antibodies in colostrum, and neutralizing antibodies in serum, of sows vaccinated with HPMCP (aP2) plus LL RANKL increased significantly at 4 weeks post-first vaccination. Furthermore, the survival rate of newborn suckling piglets delivered by sows vaccinated with HPMCP (aP2) plus LL RANKL was similar to that of piglets delivered by sows vaccinated with a commercial killed porcine epidemic diarrhea virus (PED) vaccine. The South Korean government promotes a PED vaccine program (live-killed-killed) to increase the titers of IgA and IgG antibodies in pregnant sows and prevent PEDV. The oral vaccine strategy described herein, which is based on a safe and efficient recombinant subunit antigen, is an alternative PED vaccination strategy that could replace the traditional strategy, which relies on attenuated live oral vaccines or artificial infection with virulent PEDV.",2020,"Choe, SeEun; Song, Sok; Piao, Dachuan; Park, Gyu-Nam; Shin, Jihye; Choi, Yun-Jaie; Kang, Sang-Kee; Cha, Ra Mi; Hyun, Bang-Hun; Park, Bong-Kyun; An, Dong-Jun",Veterinary Microbiology,3005277414,#2324,
,CZI,Swine acute diarrhea syndrome coronavirus (SADS-CoV) antagonizes interferon-β production via blocking IPS-1 and RIG-I,10.1016/j.virusres.2019.197843,,,,"Swine acute diarrhea syndrome coronavirus (SADS-CoV), a newly emerging enteric coronavirus, is considered to be associated with swine acute diarrhea syndrome (SADS) which has caused significantly economic losses to the porcine industry. Interactions between SADS-CoV and the host innate immune response is unclear yet. In this study, we used IPEC-J2 cells as a model to explore potential evasion strategies employed by SADS-CoV. Our results showed that SADS-CoV infection failed to induce IFN-β production, and inhibited poly (I:C) and Sendai virus (SeV)-triggered IFN-β expression. SADS-CoV also blocked poly (I:C)-induced phosphorylation and nuclear translocation of IRF-3 and NF-κB. Furthermore, SADS-CoV did not interfere with the activity of IFN-β promoter stimulated by IRF3, TBK1 and IKKε, but counteracted its activation induced by IPS-1 and RIG-I. Collectively, this study is the first investigation that shows interactions between SADS-CoV and the host innate immunity, which provides information of the molecular mechanisms underlying SASD-CoV infection.",2020,"Zhou, Zhihai; Sun, Yuan; Yan, Xiaoling; Tang, Xiaoyu; Li, Qianniu; Tan, Yaorong; Lan, Tian; Ma, Jingyun",Virus Research,,#2043,
,CZI,"Genetic characterization and phylogenetic analysis of porcine deltacoronavirus (PDCoV) in Shandong Province, China",10.1016/j.virusres.2020.197869,,,,"Porcine deltacoronavirus (PDCoV) is the etiological agent of acute diarrhoea and vomiting in pigs, threatening the swine industry worldwide. Although several PDCoV studies have been conducted in China, more sequence information is needed to understand the molecular characterization of PDCoV. In this study, the partial ORF1a, spike protein (S) and nucleocapsid protein (N) were sequenced from Shandong Province between 2017 and 2018. The sequencing results for the S protein from 10 PDCoV strains showed 96.7 %–99.7 % nucleotide sequence identity with the China lineage strains, while sharing a lower level of nucleotide sequence identity, ranging from 95.7 to 96.8%, with the Vietnam/Laos/Thailand lineage strains. N protein sequencing analysis showed that these strains showed nucleotide homologies of 97.3%–99.3% with the reference strains. Phylogenetic analyses based on S protein sequences showed that these PDCoV strains were classified into the China lineage. The discontinuous 2 + 3 aa deletions at 400–401 and 758–760 were found in the Nsp2 and Nsp3 coding region in five strains, respectively, with similar deletions having been identified in Vietnam, Thailand, and Laos. Three novel patterns of deletion were observed for the first time in the Nsp2 and Nsp3 regions. Importantly, those findings suggest that PDCoV may have undergone a high degree of variation since PDCoV was first detected in China.",2020,"Sun, Wenchao; Wang, Li; Huang, Haixin; Wang, Wei; Cao, Liang; Zhang, Jinyong; Zheng, Min; Lu, Huijun",Virus Research,3000185706,#2388,
,CZI,The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines,10.1016/S0140-6736(03)13412-5,,,,"The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern. However, no specific antiviral treatments or vaccines are available yet. This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2. An outbreak of 2019-novel coronavirus (SARS-CoV-2) that causes atypical pneumonia (COVID-19) has raged in China since mid-December 2019 and has spread to 26 countries (February 20, 2020). The epidemic was identified by the first four cases confirmed on December 29, 2019 and was traced to the Huanan Seafood Wholesale Market, Wuhan city, Hubei Province, China1. A total of 75,465 cases with SARS-CoV-2 infections have been confirmed up to date (February 20, 2020), and 2,236 people have died in China2. COVID-19 spreads rapidly by human-to-human transmission with a median incubation period of 3.0 days (range, 0 to 24.0), and the time from symptom onset to developing pneumonia is 4.0 days (range, 2.0 to 7.0)3. Respiratory droplets and direct contact are conventional transmission routes for SARS-CoV-2, and fecal-to-oral transmission might also have a role3. Fever, dry cough, and fatigue are common symptoms at onset of COVID-194. Most patients have lymphopenia and bilateral ground-glass opacity changes on chest CT scans4,5. No specific antiviral treatments or vaccines are available because it is a new emerging viral disease. Development of SARS-CoV-2-based vaccines is urgently required. The entire virus particle-based preparation of vaccines, including inactivated and attenuated virus vaccines is advisable, because it is based on previous studies about the prevention and control of seasonal influenza vaccines6. The first SARS-CoV-2 (Wuhan-Hu-1) was successfully sequenced and its genomic sequence submitted to GenBank on January 5, 2020 (Accession no. MN908947.3)7. Subsequently large-scale culture of SARS-CoV-2 was quickly performed, and an inactivated virus vaccine could be prepared through the employment of established physical and chemical methods such as UV light, formaldehyde, and β-propiolactone8. The development of attenuated-virus vaccines is also possible by carefully screening the serially propagated SARS-CoV-2 with reduced pathogenesis such as induced minimal lung injury, diminished limited neutrophil influx, and increased anti-inflammatory cytokine expressions compared with the wild-type virus9. Both inactivated and attenuated virus vaccines have their own disadvantages and side effects (Table 1). Alternatively, new vaccine designs based on the putative protective antigen/peptides derived from SARS-CoV-2 should be considered",2020,"Shang, Weilong; Yang, Yi; Rao, Yifan; Rao, Xiancai",,2129542667,#5211,
,CZI,Viral Load Kinetics of SARS-CoV-2 Infection in First Two Patients in Korea,10.1016/S0140-6736(07)60497-8,,32080991,,"As of February 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak started in China in December 2019 has been spreading in many countries in the world.With the numbers of confirmed cases are increasing, information on the epidemiologic investigation and clinical manifestation have been accumulated. However, data on viral load kinetics in confirmed cases are lacking. Here, we present the viral load kinetics of the first two confirmed patients with mild to moderate illnesses in Korea in whom distinct viral load kinetics are shown. This report suggests that viral load kinetics of SARS-CoV-2 may be different from that of previously reported other coronavirus infections such as SARS-CoV.",2020,"Kim, Jin Yong",Journal of Korean Medical Science,2139772076,#3706,
,CZI,Middle East respiratory syndrome,10.1016/S0140-6736(19)33221-0,,,,"The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.",,"Memish, Ziad A.; Perlman, Stanley; Van Kerkhove, Maria D.; Zumla, Alimuddin",The Lancet,2112147913,#3836,
,CZI,Responding to health emergencies in the Eastern Mediterranean region in times of conflict,10.1016/S0140-6736(20)30069-6,,,,"WHO's Eastern Mediterranean region (EMR) is facing emergencies on a scale that is perhaps unprecedented in its history. There is armed conflict in 12 of the region's 22 countries.1 , 2 The region's 680 million people3 represent 9% of the global population, yet the EMR is home to 43% of those who need humanitarian assistance4 and is the source of 64% of the world's refugees.5 The health effects of these crises are immense. Direct health consequences include trauma-related deaths and disability, gender-based violence, and mental disorders. Disruption of health systems contributes to increased morbidity and mortality from infectious diseases, malnutrition, obstetric complications, and non-communicable diseases (NCDs). Health indicators in the EMR are among the worst in the world.6 State fragility and conflict are among the biggest challenges to attainment of Sustainable Development Goal 3.7 Conflict is a global health security threat because affected countries are less able to prevent, detect, and respond to disease outbreaks. More than 70% of disease outbreaks worldwide occur in fragile and conflict-affected settings.8 Yemen has experienced the largest cholera outbreak in history.9 During the second half of 2019, there were six concurrent disease outbreaks in Sudan.10 Wild polio virus returned to Syria due to conflict,11 while Afghanistan and Pakistan are two of three countries where the virus remains endemic.12 The average International Health Regulations (IHR) core capacity score is much lower for the 12 conflict-affected countries than for the other countries in the region,6 placing them at greater risk of spread and public health consequences of the ongoing outbreak of coronavirus disease 2019 (COVID-19) and other epidemic-prone diseases. WHO's global COVID-19 strategic preparedness and response plan13 therefore prioritises countries with weak health systems for technical and operational support from international partners. COVID-19 has already affected ten countries in the region, as of Feb 28, 2020, including Afghanistan, Iraq, and Pakistan.",,"Brennan, Richard; Hajjeh, Rana; Al-Mandhari, Ahmed",The Lancet,2508300253,#3209,
,CZI,A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster,10.1016/S0140-6736(20)30154-9,,,,"BackgroundAn ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date.",,"Chan, Jasper Fuk-Woo; Yuan, Shuofeng; Kok, Kin-Hang; To, Kelvin Kai-Wang; Chu, Hin; Yang, Jin; Xing, Fanfan; Liu, Jieling; Yip, Cyril Chik-Yan; Poon, Rosana Wing-Shan; Tsoi, Hoi-Wah; Lo, Simon Kam-Fai; Chan, Kwok-Hung; Poon, Vincent Kwok-Man; Chan, Wan-Mui; Ip, Jonathan Daniel; Cai, Jian-Piao; Cheng, Vincent Chi-Chung; Chen, Honglin; Hui, Christopher Kim-Ming; Yuen, Kwok-Yung",The Lancet,3002539152,#20,
,CZI,"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China",10.1016/S0140-6736(20)30183-5,,31986264,,"A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients.|All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not.|By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα.|The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies.|Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.",2020,"Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; Cheng, Z.; Yu, T.; Xia, J.; Wei, Y.; Wu, W.; Xie, X.; Yin, W.; Li, H.; Liu, M.; Xiao, Y.; Gao, H.; Guo, L.; Xie, J.; Wang, G.; Jiang, R.; Gao, Z.; Jin, Q.; Wang, J.; Cao, B.",Lancet,3001118548,#34,
,CZI,Analysis of clinical features of 153 patients with novel coronavirus pneumonia in Chongqing,10.1016/S0140-6736(20)30183-5,,,,"Objective To analyze the clinical data of 153 patients with novel coronavirus pneumonia (COVID-19) in chongqing ,and provide reference and thinking for the diagnosis and treatment. Methods Analyze the clinical data, laboratory examination and chest imaging characteristics of 153 COVID-19 patients in Chongqing Public Health Medical Center from January 26 to February 5, 2020. According to the relevant diagnostic criteria ,patients were divided into non-severe group(n=132) and severe group(n=21),and analyze the correlation between serum index changes and disease severity. Results Combined with diabetes and chronic respiratory diseases, the severity of the disease was statistically significant ( χ 2 =11.04和6.94, P <0.05). No symptoms were found in patients with mild illness ( χ 2 =4.09, P <0.05) .The proportion of fever and muscle soreness in the severe group was higher than that in the non-severe group ( χ 2 =4.40 and 22.67, P <0.05).Among the concomitant symptoms, the proportion of cough and shortness of breath in the severe group was higher than that in the non-severe group ( χ 2 =8.46 and 4.80, P <0.05).C-reactive protein and d-dimer were higher in the severe group than in the non-severe group ( t =43.44 and 37.13, P <0.05), and the number of CD 3 + T lymphocyte cells, CD 4 + T lymphocyte cells and CD 8 + T lymphocyte cells in the severe group was lower than that in the non-severe group (Z=27.25, 20.60 and 17.36, P <0.05).Compared with the non-severe group, both lungs and the right lung lower lobe were more susceptible to involved ( χ 2 =6.95和20.39, P <0.05) . Conclusion Severity of COVID-19 was associated with underlying disease, symptoms, site of involvement, C-reactive protein, d-dimer, CD 3 + T lymphocyte count, CD 4 + T lymphocyte count, and CD 8 + T lymphocyte count. ",2020,"WAN, Qiu",Chinese Journal of Clinical Infectious Diseases,3001118548,#2137,
,CZI,Clinical features of 2019 novel coronavirus infection patients and a feasible screening procedure,10.1016/S0140-6736(20)30183-5,,,,"Objective To study the clinical characteristics of 2019 coronavirus (2019-nCoV) pneumonia patients and make a feasible screening process in fever clinic. Methods Epidemiologic features, clinical presentation, laboratory findings and image features of the screened patients were retrospectively collected and analyzed. Results Totally, 46 patients were screened, 9 of them were laboratory-confirmed 2019-nCoV infection, and others were defined as laboratory-excluded patients. Laboratory-confirmed patients had higher frequency of travelling or residence in Wuhan within two weeks of onset (P<0.05), but there were no differences on age, sex, other epidemiologic features and comorbidities between the two groups (P>0.05). The most common feature of the laboratory-confirmed patients was fever (100%), but the symptoms showed no differences between the two groups (P>0.05). Laboratory-confirmed patients had lower white blood cell count than the laboratory-excluded patients (P<0.05), and all of them had pneumonia in chest CT scan. None of the patients with normal chest CT had positive 2019-nCoV nucleic acid test. Conclusions No specific symptom was helpful in the diagnosis of 2019-nCoV infection. However, patients without chest CT scan changes had a very low risk of 2019-nCoV infection despite of the epidemiologic history and fever. We recommended a screening procedure that might be helpful to reduce the rate of miss diagnosis and improve screening efficiency.",2020,"LI, Yan; XU, Shengyong; DU, Tiekuan; XU, Jun; LI, Yi; YU, Xuezhong; ZHU, Huadong",Chinese Journal of Emergency Medicine,3001118548,#2201,
,CZI,Data sharing and outbreaks: best practice exemplified,10.1016/S0140-6736(20)30184-7,,,,,2020,"Heymann, David L.",The Lancet,3001293154,#844,
,CZI,Emerging understandings of 2019-nCoV,10.1016/S0140-6736(20)30186-0,,31986259,,,2020,The Lancet,Lancet,3004668429,#25,
,CZI,"Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study",10.1016/S0140-6736(20)30211-7,,,,"BackgroundIn December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia.",,"Chen, Nanshan; Zhou, Min; Dong, Xuan; Qu, Jieming; Gong, Fengyun; Han, Yang; Qiu, Yang; Wang, Jingli; Liu, Ying; Wei, Yuan; Xia, Jia'an; Yu, Ting; Zhang, Xinxin; Zhang, Li",The Lancet,3002108456,#78,
,CZI,Clinical research progresss of antiviral drugs for the novel coronavirus pneumonia,10.1016/S0140-6736(20)30211-7,,,,"The novel coronavirus (2019-nCoV or SARS-CoV-2) is a highly contagious and deadly virus that has infected more than 50 000 people and killed more than 1 000 people in 25 countries around the world. People who infected by the novel coronavirus may suffer from fever and cough, some may gradually appear breathing difficulties and other serious manifestations, some severe patients may have acute respiratory distress syndrome and septic shock leading to death. However, there are no definite and effective antiviral drugs for the novel coronavirus pneumonia all around the world. Therefore, this article aims to provide new idea for the effective treatment of the novel coronavirus pneumonia by summarizing the basic research and clinical progress of antiviral drugs at home and abroad.",2020,"WU, Weigang; YANG, Guilin; ZENG, Xiaobin; WU, Shipin; ZHOU, Boping",Chinese Journal of Experimental and Clinical Virology,3002108456,#2120,
,CZI,Offline: 2019-nCoV outbreak—early lessons,10.1016/S0140-6736(20)30212-9,,,,,2020,"Horton, Richard",The Lancet,3004037946,#77,
,CZI,A novel coronavirus outbreak of global health concern - Comment - Correction,10.1016/S0140-6736(20)30250-6,,,,"Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet 2020; published online Jan 24. https://dox.doi.org/S0140-6736(20)30185-9—In this. Comment, the first sentence of the third paragraph should have read “Of the 41 patients in this cohort, 22 (55%) developed severe dyspnoea and 13 (32%) required admission to an intensive care unit, and six died.” And in the table, the title of the third row should have read “Location of first detection”. These corrections have been made to the online version as of Jan 29, 2020, and will be made to the printed version.",2020,"Chen Wang, Peter W Horby, Frederick G Hayden, George F Gao",The Lancet,3001465255,#847,
,CZI,Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding,10.1016/S0140-6736(20)30251-8,,,,"BackgroundIn late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed.",,"Lu, Roujian; Zhao, Xiang; Li, Juan; Niu, Peihua; Yang, Bo; Wu, Honglong; Wang, Wenling; Song, Hao; Huang, Baoying; Zhu, Na; Bi, Yuhai; Ma, Xuejun; Zhan, Faxian; Wang, Liang; Hu, Tao; Zhou, Hong; Hu, Zhenhong; Zhou, Weimin; Zhao, Li; Chen, Jing; Meng, Yao; Wang, Ji; Lin, Yang; Yuan, Jianying; Xie, Zhihao; Ma, Jinmin; Liu, William J.; Wang, Dayan; Xu, Wenbo; Holmes, Edward C.; Gao, George F.; Wu, Guizhen; Chen, Weijun; Shi, Weifeng; Tan, Wenjie",The Lancet,3004318991,#80,
,CZI,"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China (vol 395, pg 497, 2020)",10.1016/s0140-6736(20)30252-x,,,,,2020,"Huang, C.; Wang, Y.; Li, X.",Lancet,3001118548,#3649,
,CZI,"Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study",10.1016/S0140-6736(20)30260-9,,,,"Summary Background Since Dec 31, 2019, the Chinese city of Wuhan has reported an outbreak of atypical pneumonia caused by the 2019 novel coronavirus (2019-nCoV). Cases have been exported to other Chinese cities, as well as internationally, threatening to trigger a global outbreak. Here, we provide an estimate of the size of the epidemic in Wuhan on the basis of the number of cases exported from Wuhan to cities outside mainland China and forecast the extent of the domestic and global public health risks of epidemics, accounting for social and non-pharmaceutical prevention interventions. Methods We used data from Dec 31, 2019, to Jan 28, 2020, on the number of cases exported from Wuhan internationally (known days of symptom onset from Dec 25, 2019, to Jan 19, 2020) to infer the number of infections in Wuhan from Dec 1, 2019, to Jan 25, 2020. Cases exported domestically were then estimated. We forecasted the national and global spread of 2019-nCoV, accounting for the effect of the metropolitan-wide quarantine of Wuhan and surrounding cities, which began Jan 23–24, 2020. We used data on monthly flight bookings from the Official Aviation Guide and data on human mobility across more than 300 prefecture-level cities in mainland China from the Tencent database. Data on confirmed cases were obtained from the reports published by the Chinese Center for Disease Control and Prevention. Serial interval estimates were based on previous studies of severe acute respiratory syndrome coronavirus (SARS-CoV). A susceptible-exposed-infectious-recovered metapopulation model was used to simulate the epidemics across all major cities in China. The basic reproductive number was estimated using Markov Chain Monte Carlo methods and presented using the resulting posterior mean and 95% credibile interval (CrI). Findings In our baseline scenario, we estimated that the basic reproductive number for 2019-nCoV was 2·68 (95% CrI 2·47–2·86) and that 75 815 individuals (95% CrI 37 304–130 330) have been infected in Wuhan as of Jan 25, 2020. The epidemic doubling time was 6·4 days (95% CrI 5·8–7·1). We estimated that in the baseline scenario, Chongqing, Beijing, Shanghai, Guangzhou, and Shenzhen had imported 461 (95% CrI 227–805), 113 (57–193), 98 (49–168), 111 (56–191), and 80 (40–139) infections from Wuhan, respectively. If the transmissibility of 2019-nCoV were similar everywhere domestically and over time, we inferred that epidemics are already growing exponentially in multiple major cities of China with a lag time behind the Wuhan outbreak of about 1–2 weeks. Interpretation Given that 2019-nCoV is no longer contained within Wuhan, other major Chinese cities are probably sustaining localised outbreaks. Large cities overseas with close transport links to China could also become outbreak epicentres, unless substantial public health interventions at both the population and personal levels are implemented immediately. Independent self-sustaining outbreaks in major cities globally could become inevitable because of substantial exportation of presymptomatic cases and in the absence of large-scale public health interventions. Preparedness plans and mitigation interventions should be readied for quick deployment globally. Funding Health and Medical Research Fund (Hong Kong, China).",2020,"Wu, Joseph T.; Leung, Kathy; Leung, Gabriel M.",The Lancet,3003573988,#106,
,CZI,What next for the coronavirus response?,10.1016/S0140-6736(20)30292-0,,,,,2020,"Zarocostas, John",The Lancet,3005352349,#356,
,CZI,Offline: 2019-nCoV—“A desperate plea”,10.1016/S0140-6736(20)30299-3,,,,,2020,"Horton, Richard",The Lancet,,#407,
,CZI,What to do next to control the 2019-nCoV epidemic?,10.1016/S0140-6736(20)30300-7,,,,,2020,"Wang, Fu-Sheng; Zhang, Chao",The Lancet,3005057182,#367,
,CZI,"Department of Error: Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study (The Lancet (2020) 395(10225) (689–697), (S0140673620302609), (10.1016/S0140-6736(20)30260-9))",10.1016/S0140-6736(20)30302-0,,,,"Wu JT, Leung K, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. Lancet 2020; published online Jan 31. https://doi.org/10.1016/10.1016/S0140-6736(20)30260-9—In this Article, the data sharing statement has been amended to clarify the sources from which data can be obtained. This correction has been made to the online version as of Feb 4, 2020, and will be made to the printed version.",2020,,The Lancet,,#2997,
,CZI,Baricitinib as potential treatment for 2019-nCoV acute respiratory disease,10.1016/S0140-6736(20)30304-4,,,,,2020,"Richardson, Peter; Griffin, Ivan; Tucker, Catherine; Smith, Dan; Oechsle, Olly; Phelan, Anne; Stebbing, Justin",The Lancet,3004919484,#217,
,CZI,Reducing mortality from 2019-nCoV: host-directed therapies should be an option,10.1016/S0140-6736(20)30305-6,,,,,2020,"Zumla, Alimuddin; Hui, David S.; Azhar, Esam I.; Memish, Ziad A.; Maeurer, Markus",The Lancet,3004743633,#244,
,CZI,Full spectrum of COVID-19 severity still being depicted,10.1016/S0140-6736(20)30308-1,,,,,,"Xu, Zhou; Li, Shu; Tian, Shen; Li, Hao; Kong, Ling-quan",The Lancet,3006304557,#898,
,CZI,2019-nCoV epidemic: address mental health care to empower society,10.1016/S0140-6736(20)30309-3,,,,,,"Bao, Yanping; Sun, Yankun; Meng, Shiqiu; Shi, Jie; Lu, Lin",The Lancet,3005380688,#527,
,CZI,2019-nCoV epidemic: what about pregnancies?,10.1016/S0140-6736(20)30311-1,,,,,2020,"Favre, Guillaume; Pomar, Léo; Musso, Didier; Baud, David",The Lancet,3005113694,#411,
,CZI,2019-nCoV transmission through the ocular surface must not be ignored,10.1016/S0140-6736(20)30313-5,,,,,,"Lu, Cheng-wei; Liu, Xiu-fen; Jia, Zhi-fang",The Lancet,3005091255,#390,
,CZI,Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury,10.1016/S0140-6736(20)30317-2,,,,,,"Russell, Clark D.; Millar, Jonathan E.; Baillie, J. Kenneth",The Lancet,3005403371,#523,
,CZI,From Hendra to Wuhan: what has been learned in responding to emerging zoonotic viruses,10.1016/S0140-6736(20)30350-0,,,,,2020,"Wang, Lin-Fa; Anderson, Danielle E.; Mackenzie, John S.; Merson, Michael H.",The Lancet,3005787104,#721,
,CZI,Africa prepares for coronavirus,10.1016/S0140-6736(20)30355-X,,,,,2020,"Makoni, Munyaradzi",The Lancet,3006009475,#839,
,CZI,Early lessons from the frontline of the 2019-nCoV outbreak,10.1016/S0140-6736(20)30356-1,,,,,2020,"Zhang, Hong",The Lancet,3005675140,#711,
,CZI,"2019-nCoV, fake news, and racism",10.1016/S0140-6736(20)30357-3,,,,,2020,"Shimizu, Kazuki",The Lancet,3005716085,#731,
,CZI,Anti-Chinese sentiment during the 2019-nCoV outbreak,10.1016/S0140-6736(20)30358-5,,,,,2020,"Chung, Roger Yat-Nork; Li, Minnie Ming",The Lancet,3005805019,#787,
,CZI,Minimise nosocomial spread of 2019-nCoV when treating acute respiratory failure,10.1016/S0140-6736(20)30359-7,,,,,2020,"Cabrini, Luca; Landoni, Giovanni; Zangrillo, Alberto",The Lancet,3005875949,#793,
,CZI,Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records,10.1016/S0140-6736(20)30360-3,,,,"Summary Background Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection. Methods Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation. Findings All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0 × 10⁹ cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8–9 and a 5-min Apgar score of 9–10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus. Interpretation The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy. Funding Hubei Science and Technology Plan, Wuhan University Medical Development Plan.",2020,"Chen, Huijun; Guo, Juanjuan; Wang, Chen; Luo, Fan; Yu, Xuechen; Zhang, Wei; Li, Jiafu; Zhao, Dongchi; Xu, Dan; Gong, Qing; Liao, Jing; Yang, Huixia; Hou, Wei; Zhang, Yuanzhen",The Lancet,3005679569,#789,
,CZI,On the use of corticosteroids for 2019-nCoV pneumonia,10.1016/S0140-6736(20)30361-5,,,,,2020,"Shang, Lianhan; Zhao, Jianping; Hu, Yi; Du, Ronghui; Cao, Bin",The Lancet,3005905966,#733,
,CZI,Offline: How to defeat political populism,10.1016/S0140-6736(20)30363-9,,,,,2020,"Horton, Richard",The Lancet,3005799376,#842,
,CZI,What are the risks of COVID-19 infection in pregnant women?,10.1016/S0140-6736(20)30365-2,,,,,2020,"Qiao, Jie",The Lancet,3006304225,#741,
,CZI,"First imported case of 2019 novel coronavirus in Canada, presenting as mild pneumonia",10.1016/S0140-6736(20)30370-6,,,,,2020,"Silverstein, William Kyle; Stroud, Lynfa; Cleghorn, Graham Edward; Leis, Jerome Allen",The Lancet,3006411443,#836,
,CZI,Full spectrum of COVID-19 severity still being depicted – Authors' reply,10.1016/S0140-6736(20)30371-8,,,,,,"Gu, Xiaoying; Cao, Bin; Wang, Jianwei",The Lancet,3006017470,#978,
,CZI,Do not violate the International Health Regulations during the COVID-19 outbreak,10.1016/S0140-6736(20)30373-1,,,,,2020,"Habibi, Roojin; Burci, Gian Luca; de Campos, Thana C.; Chirwa, Danwood; Cinà, Margherita; Dagron, Stéphanie; Eccleston-Turner, Mark; Forman, Lisa; Gostin, Lawrence O.; Meier, Benjamin Mason; Negri, Stefania; Ooms, Gorik; Sekalala, Sharifah; Taylor, Allyn; Yamin, Alicia Ely; Hoffman, Steven J.",The Lancet,3006304371,#845,
,CZI,COVID-19: what is next for public health?,10.1016/s0140-6736(20)30374-3,,,,"The WHO Scientific and Technical Advisory Group for Infectious Hazards (STAG-IH), working with the WHO secretariat, reviewed available information about the outbreaks of 2019 novel coronavirus disease (COVID-19) on Feb 7, 2020, in Geneva, Switzerland, and concluded that the continuing strategy of containment for elimination should continue, and that the coming 2–3 weeks through to the end of February, 2020, will be crucial to monitor the situation of community transmission to update WHO public health recommendations if required.",2020,"Heymann, David L.; Shindo, Nahoko; Bedford, Juliet; Enria, Delia; Giesecke, Johan; Heymann, David; Ihekweazu, Chikwe; Kobinger, Gary; Lane, Clifford; Memish, Ziad; Myoung-don, Oh; Sall, Amadou Alpha; Ungchusak, Kum; Wieler, Lothar; Infect, W. H. O. Sci Tech Advisory Grp",Lancet,3005995896,#3637,
,CZI,COVID-19 Update From China,10.1016/S0140-6736(20)30375-5,,,,"By mid-February 2020 there were 60,000 confirmed cases of COVID-19, the vast majority diagnosed in Hubei Province (including Wuhan city) in mainland China. China CDC Chief Epidemiologist Zunyou Wu, MD, PhD discusses the latest COVID-19 developments in the country with JAMA Editor in Chief Howard Bauchner, MD.",2020,JAMA,JAMA,3005550222,#887,
,CZI,Timely research papers about COVID-19 in China,10.1016/S0140-6736(20)30375-5,,,,,,"Xiang, Yu-Tao; Li, Wen; Zhang, Qinge; Jin, Yu; Rao, Wen-Wang; Zeng, Liang-Nan; Lok, Grace K. I.; Chow, Ines H. I.; Cheung, Teris; Hall, Brian J.",The Lancet,3005550222,#1088,
,CZI,COVID-19: fighting panic with information,10.1016/S0140-6736(20)30379-2,,,,,2020,"The, Lancet",The Lancet,3006304371,#1357,
,CZI,Offline: Facts are not enough,10.1016/S0140-6736(20)30405-0,,,,,2020,"Horton, Richard",The Lancet,2035283980,#1628,
,CZI,Preparedness and vulnerability of African countries against importations of COVID-19: a modelling study,10.1016/S0140-6736(20)30411-6,,,,,2020,"Marius Gilbert, Giulia Pullano, Francesco Pinotti, Eugenio Valdano, Chiara Poletto, Pierre-Yves Boëlle, Eric D’Ortenzio, Yazdan Yazdanpanah,; Serge Paul Eholie, Mathias Altmann, Bernardo Gutierrez, Moritz U G Kraemer, Vittoria Colizza",The Lancet,3004759370,#1335,
,CZI,"Statement in support of the scientists, public health professionals, and medical professionals of China combatting COVID-19",10.1016/S0140-6736(20)30418-9,,,,,2020,"Calisher, Charles; Carroll, Dennis; Colwell, Rita; Corley, Ronald B.; Daszak, Peter; Drosten, Christian; Enjuanes, Luis; Farrar, Jeremy; Field, Hume; Golding, Josie; Gorbalenya, Alexander; Haagmans, Bart; Hughes, James M.; Karesh, William B.; Keusch, Gerald T.; Lam, Sai Kit; Lubroth, Juan; Mackenzie, John S.; Madoff, Larry; Mazet, Jonna; Palese, Peter; Perlman, Stanley; Poon, Leo; Roizman, Bernard; Saif, Linda; Subbarao, Kanta; Turner, Mike",The Lancet,2287268028,#1326,
,CZI,Scientists are sprinting to outpace the novel coronavirus,10.1016/S0140-6736(20)30420-7,,,,,2020,"Ghebreyesus, Tedros Adhanom; Swaminathan, Soumya",The Lancet,2314463002,#1846,
,CZI,COVID-19 control in China during mass population movements at New Year,10.1016/S0140-6736(20)30421-9,,,,"Government policies enacted during the Chinese Lunar New Year holiday are likely to have helped reduce the spread of the virus by decreasing contact and increasing physical distance between those who have COVID-19 and those who do not. As part of these social distancing policies, the Chinese Government encouraged people to stay at home; discouraged mass gatherings; cancelled or postponed large public events; and closed schools, universities, government offices, libraries, museums, and factories. Only limited segments of urban public transport systems remained operational and all cross-province bus routes were taken out of service. As a result of these policies and public information and education campaigns, Chinese citizens started to take measures to protect themselves against COVID-19, such as staying at home as far as possible, limiting social contacts, and wearing protective masks when they needed to move in public.",,"Chen, Simiao; Yang, Juntao; Yang, Weizhong; Wang, Chen; Bärnighausen, Till",The Lancet,1220324463,#2005,
,CZI,The danger of stories in global health,10.1016/S0140-6736(20)30427-X,,,,,2020,"Harman, Sophie",The Lancet,2896599320,#4565,
,CZI,Indian pharma threatened by COVID-19 shutdowns in China,10.1016/S0140-6736(20)30459-1,,,,"As factories in China are closed, India is working to maintain supplies of active pharmaceutical ingredients. Patralekha Chatterjee reports from New Delhi. India supplies low-cost generic drugs to millions of people, both within and outside the country. But Indian pharmaceutical companies procure almost 70% of the active pharmaceutical ingredients (APIs) for their medicines from China, the world's leading producer and exporter of APIs by volume. As factories in China are closed to try to stem the coronavirus disease 2019 outbreak, pharmaceutical companies and the Indian Government are becoming concerned over the vulnerability of the Indian pharmaceutical supply chain.",2020,"Chatterjee, Patralekha",The Lancet,819170924,#2755,
,CZI,The psychological impact of quarantine and how to reduce it: rapid review of the evidence,10.1016/S0140-6736(20)30460-8,,,,"The December, 2019 coronavirus disease outbreak has seen many countries ask people who have potentially come into contact with the infection to isolate themselves at home or in a dedicated quarantine facility. Decisions on how to apply quarantine should be based on the best available evidence. We did a Review of the psychological impact of quarantine using three electronic databases. Of 3166 papers found, 24 are included in this Review. Most reviewed studies reported negative psychological effects including post-traumatic stress symptoms, confusion, and anger. Stressors included longer quarantine duration, infection fears, frustration, boredom, inadequate supplies, inadequate information, financial loss, and stigma. Some researchers have suggested long-lasting effects. In situations where quarantine is deemed necessary, officials should quarantine individuals for no longer than required, provide clear rationale for quarantine and information about protocols, and ensure sufficient supplies are provided. Appeals to altruism by reminding the public about the benefits of quarantine to wider society can be favourable.",,"Brooks, Samantha K.; Webster, Rebecca K.; Smith, Louise E.; Woodland, Lisa; Wessely, Simon; Greenberg, Neil; Rubin, Gideon James",The Lancet,3006659024,#2354,
,CZI,How to fight an infodemic,10.1016/S0140-6736(20)30461-X,,,,"WHO's newly launched platform aims to combat misinformation around COVID-19. John Zarocostas reports from WHO is leading the effort to slow the spread of the 2019 coronavirus disease (COVID-19) outbreak. But a global epidemic of misinformation—spreading rapidly through social media platforms and other outlets—poses a serious problem for public health. “We’re not just fighting an epidemic; we’re fighting an infodemic”, said WHO Director-General Tedros Adhanom Ghebreyesus at the Munich Security Conference on Feb 15. Immediately after COVID-19 was declared a Public Health Emergency of International Concern, WHO's risk communication team launched a new information platform called WHO Information Network for Epidemics (EPI-WIN), with the aim of using a series of amplifiers to share tailored information with specific target groups. Sylvie Briand, director of Infectious Hazards Management at WHO's Health Emergencies Programme and architect of WHO's strategy to counter the infodemic risk, told The Lancet, “We know that every outbreak will be accompanied by a kind of tsunami of information, but also within this information you always have misinformation, rumours, etc. We know that even in the Middle Ages there was this phenomenon”. “But the difference now with social media is that this phenomenon is amplified, it goes faster and further, like the viruses that travel with people and go faster and further. So it is a new challenge, and the challenge is the [timing] because you need to be faster if you want to fill the void…What is at stake during an outbreak is making sure people will do the right thing to control the disease or to mitigate its impact. So it is not only information to make sure people are informed; it is also making sure people are informed to act appropriately.” About 20 staff and some consultants are involved in WHO's communications teams globally, at any given time. This includes social media personnel at each of WHO's six regional offices, risk communications consultants, and WHO communications officers.",2020,"Zarocostas, John",The Lancet,2799474450,#3015,
,CZI,Secondary attack rate and superspreading events for SARS-CoV-2,10.1016/S0140-6736(20)30462-1,,,,,2020,"Liu, Yang; Eggo, Rosalind M.; Kucharski, Adam J.",The Lancet,2121671559,#2593,
,CZI,Lessons for managing high-consequence infections from first COVID-19 cases in the UK,10.1016/S0140-6736(20)30463-3,,,,"These first UK cases of COVID-19 raise important points about the management of cases of HCID in England. The decision to test for SARS-CoV-2 is based on a clinical and epidemiological case definition, and testing is only approved if this is met. When tested, neither of these people clearly met the current case definition, and had criteria been strictly applied, testing might not have been done. A decision to test was made because of high clinical suspicion and in response to latest available information about the distribution of infection. It is important that testing is appropriately targeted, and this is best done by applying clear case definitions. However, with any newly emerging infection, case definitions must evolve rapidly as information accrues. There should also be room for flexibility on the basis of discussion with clinical and public health experts",,"Moss, Peter; Barlow, Gavin; Easom, Nicholas; Lillie, Patrick; Samson, Anda",The Lancet,2217820961,#2702,
,CZI,"Looming threat of COVID-19 infection in Africa: act collectively, and fast",10.1016/S0140-6736(20)30464-5,,,,"Models that enable the continent to better allocate scarce resources to better prepare and respond to the COVID-19 epidemic are crucial. The modelling study by Marius Gilbert and colleagues in The Lancet identifies each African country's risk of importation of COVID-19 from China, using data on the volume of air travel from three airports in provinces in China to African countries. Gilbert and colleagues use two indicators to determine the capacity of countries to detect and respond to cases: preparedness, using the WHO International Health Regulations Monitoring and Evaluation Framework; and vulnerability, using the Infectious Disease Vulnerability Index. Based on their analysis, Egypt, Algeria, and South Africa had the highest importation risk, and a moderate to high capacity to respond to outbreaks. Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, and Kenya had moderate risk with variable capacity and high vulnerability. In the model, the risk mainly originates from Guangdong, Fujian, and Beijing. The study provides a valuable tool that can help countries in Africa prioritise and allocate resources as they prepare to respond to the potential introduction and spread of COVID-19.",,"Nkengasong, John N.; Mankoula, Wessam",The Lancet,3006304225,#2701,
,CZI,COVID-19: preparing for superspreader potential among Umrah pilgrims to Saudi Arabia,10.1016/S0140-6736(20)30466-9,,,,"The ongoing coronavirus disease 2019 (COVID-19) outbreak is a Public Health Emergency of International Concern (PHEIC), and the emergence of new epicentres of spread, such as South Korea and Iran, besides Wuhan, China, should draw attention to potential superspreader events.Of concern is the continuous Umrah pilgrimage to Saudi Arabia by Muslim pilgrims from more than 180 countries. In addition to the non-pilgrim air traffic (39 million people in 2018), Saudi Arabia received 7·5 million Umrah visa holders in 2019",,"Ebrahim, Shahul H.; Memish, Ziad A.",The Lancet,2074979691,#2703,
,CZI,COVID-19 and the anti-lessons of history,10.1016/S0140-6736(20)30468-2,,,,"As the outbreak of coronavirus disease 2019 (COVID-19) in China's Hubei province continues and new cases of the disease increase globally,1 there is pressure on historians to show the value of history for policy. How can the past assist in the real-time management of the crisis? What insights can be gleaned from the ongoing epidemic for future disease preparedness and prevention? Lurking in the background of these interrogatives is a more or less explicit accusation: why haven't past lessons been learned? The gist of some commentaries seems to be: “there is almost nothing surprising about this pandemic”.2 The history-as-lessons approach pivots on the assumption that epidemics are structurally comparable events, wherever and whenever they take place. The COVID-19 outbreak “creates a sense of déjà vu” with the 2003 outbreak of severe acute respiratory syndrome (SARS).3 Citing early estimates of the disease's infectiousness, based on an analysis of the first 425 confirmed cases in Wuhan,4 comparisons have been drawn with the 1918–19 influenza pandemic.5 Although in some respects the outbreak of COVID-19 presents a compelling argument for why history matters, there are problems with analogical views of the past because they constrain our ability to grasp the complex place-and-time-specific variables that drive contemporary disease emergence. A lessons approach to epidemics produces what Kenneth Burke, borrowing from the economist and sociologist Thorstein Veblen, called “trained incapacity”—“that state of affairs whereby one's very abilities can function as blindnesses”.6 Habitual modes of thinking can diminish our capacity to make lateral connections. When the present is viewed through the lens of former disease outbreaks, we typically focus on similitudes and overlook important differences. In other words, analogies create blind spots. As Burke commented, “a way of seeing is also a way of not seeing—a focus on object A involves a neglect of object B”.",,"Peckham, Robert",The Lancet,2116636416,#3136,
,CZI,The response of Milan's Emergency Medical System to the COVID-19 outbreak in Italy,10.1016/S0140-6736(20)30493-1,,,,"The number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), is dramatically increasing worldwide.The first person-to-person transmission in Italy was reported on Feb 21, 2020, and led to an infection chain that represents the largest COVID-19 outbreak outside Asia to date. Here we document the response of the Emergency Medical System (EMS) of the metropolitan area of Milan, Italy, to the COVID-19 outbreak.On Jan 30, 2020, WHO declared the COVID-19 outbreak a public health emergency of international concern.2 Since then, the Italian Government has implemented extraordinary measures to restrict viral spread, including interruptions of air traffic from China, organised repatriation flights and quarantines for Italian travellers in China, and strict controls at international airports' arrival terminals. Local medical authorities adopted specific WHO recommendations to identify and isolate suspected cases of COVID-19.Such recommendations were addressed to patients presenting with respiratory symptoms and who had travelled to an endemic area in the previous 14 days or who had worked in the health-care sector, having been in close contact with patients with severe respiratory disease with unknown aetiology. Suspected cases were transferred to preselected hospital facilities where the SARS-CoV-2 test was available and infectious disease units were ready for isolation of confirmed cases.",,"Spina, Stefano; Marrazzo, Francesco; Migliari, Maurizio; Stucchi, Riccardo; Sforza, Alessandra; Fumagalli, Roberto",The Lancet,2050082093,#2989,
,CZI,Mass masking in the COVID-19 epidemic: people need guidance,10.1016/S0140-6736(20)30520-1,,,,"WHO recommends against wearing masks in community settings because of lack of evidence.2 However, absence of evidence of effectiveness should not be equated to evidence of ineffectiveness, especially when facing a novel situation with limited alternative options. It has long been recommended that for respiratory infections like influenza, affected patients should wear masks to limit droplet spread. If everyone puts on a mask in public places, it would help to remove stigmatisation that has hitherto discouraged masking of symptomatic patients in many places.3 Furthermore, transmission from asymptomatic infected individuals has been documented for COVID-19, and viral load is particularly high at early disease stage.4 , 5 Masking, as a public health intervention, would probably intercept the transmission link and prevent these apparently healthy infectious sources.",,"Leung, Chi Chiu; Lam, Tai Hing; Cheng, Kar Keung",The Lancet,3006419170,#3483,
,CZI,Has China faced only a herald wave of SARS-CoV-2?,10.1016/S0140-6736(20)30521-3,,,,"The attack rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) calculated by mathematical models, from estimates of the basic reproduction number, R0, of 2–3, suggests that 50–60% of the population should eventually be infected because the population seems to be entirely naive to the new virus.1 The observed attack rate on board the Diamond Princess cruise ship remained slightly below 20% (705 of 3711 passengers and crew members became infected).1 It is of upmost importance to know whether the SARS-CoV-2 outbreak in China is subsiding, as local authorities and the entire international community might wish. With 80 026 COVID-19 cases officially reported from China as of March 2, 2020,2 the proportion of the population affected remains far from 50%, or even 20%, of China's 1·4 billion people. Has China just experienced a herald wave, to use terminology borrowed from those who study tsunamis, and is the big wave still to come? Serosurveys can help answer these questions precisely.3 To serosurvey the outbreak would involve testing sera of blood samples from the most representative sample of the population at the epicentre of the epidemic, Wuhan. Serology analysis with neutralising antibodies from the 1000 people could allow for the rate of SARS-CoV-2 infections to be estimated with good accuracy. This rate could be extrapolated to the city's entire population and thus inform more precisely whether the provisional attack rate during this period was a few cases per thousand or perhaps affected 1–2% of the population, 20%, or more. Serosurveys should be seen as polls before elections; they can be repeated several times,3 week after week, to monitor the epidemic precisely. There is no reason to wait for the end of the epidemic before doing serosurveys. The results would be tremendously informative to China, first and foremost, and to the entire international community, on the risk of big secondary epidemic waves",,"Flahault, Antoine",The Lancet,3006355661,#4102,
,CZI,"COVID-19: too little, too late?",10.1016/S0140-6736(20)30522-5,,,,,2020,"The, Lancet",The Lancet,2519393586,#4430,
,CZI,COVID-19: the gendered impacts of the outbreak,10.1016/S0140-6736(20)30526-2,,,,"Policies and public health efforts have not addressed the gendered impacts of disease outbreaks.1 The response to coronavirus disease 2019 (COVID-19) appears no different. We are not aware of any gender analysis of the outbreak by global health institutions or governments in affected countries or in preparedness phases. Recognising the extent to which disease outbreaks affect women and men differently is a fundamental step to understanding the primary and secondary effects of a health emergency on different individuals and communities, and for creating effective, equitable policies and interventions. Although sex-disaggregated data for COVID-19 show equal numbers of cases between men and women so far, there seem to be sex differences in mortality and vulnerability to the disease.2 Emerging evidence suggests that more men than women are dying, potentially due to sex-based immunological3 or gendered differences, such as patterns and prevalence of smoking.4 However, current sex-disaggregated data are incomplete, cautioning against early assumptions. Simultaneously, data from the State Council Information Office in China suggest that more than 90% of health-care workers in Hubei province are women, emphasising the gendered nature of the health workforce and the risk that predominantly female health workers incur.",,"Wenham, Clare; Smith, Julia; Morgan, Rosemary",The Lancet,3006304371,#5424,
,CZI,Mitigate the effects of home confinement on children during the COVID-19 outbreak,10.1016/S0140-6736(20)30547-X,,,,"In response to the coronavirus disease 2019 (COVID-19) outbreak, the Chinese Government has ordered a nationwide school closure as an emergency measure to prevent spreading of the infection. Public activities are discouraged. The Ministry of Education estimates that more than 220 million children and adolescents are confined to their homes; this includes 180 million primary and secondary students and 47 million preschool children).1 Thanks to the strong administrative system in China, the emergency home schooling plan has been rigorously implemented.2 Massive efforts are being made by schools and teachers at all levels to create online courses and deliver them through TV broadcasts and the internet in record time. The new virtual semester has just started in many parts of the country, and various courses are offered online in a well organised manner. These actions are helping to alleviate many parents' concerns about their children's educational attainment by ensuring that school learning is largely undisrupted. Although these measures and efforts are highly commendable and necessary, there are reasons to be concerned because prolonged school closure and home confinement during a disease outbreak might have negative effects on children's physical and mental health.3 , 4 Evidence suggests that when children are out of school (eg, weekends and summer holidays), they are physically less active, have much longer screen time, irregular sleep patterns, and less favourable diets, resulting in weight gain and a loss of cardiorespiratory fitness.3 , 5 Such negative effects on health are likely to be much worse when children are confined to their homes without outdoor activities and interaction with same aged friends during the outbreak.",,"Wang, Guanghai; Zhang, Yunting; Zhao, Jin; Zhang, Jun; Jiang, Fan",The Lancet,1968779433,#4165,
,CZI,Are high-performing health systems resilient against the COVID-19 epidemic?,10.1016/S0140-6736(20)30551-1,,,,"As of March 5, 2020, there has been sustained local transmission of coronavirus disease 2019 (COVID-19) in Hong Kong, Singapore, and Japan.1 Containment strategies seem to have prevented smaller transmission chains from amplifying into widespread community transmission. The health systems in these locations have generally been able to adapt,2 , 3 but their resilience could be affected if the COVID-19 epidemic continues for many more months and increasing numbers of people require services. We outline some of the core dimensions of these resilient health systems4 and their responses to the COVID-19 epidemic. First, after variable periods of adaptation, the three locations took actions to manage the outbreak of a new pathogen. Surveillance systems were readjusted to identify potential cases while public health staff identified their contacts. National laboratory networks developed diagnostic tests once the COVID-19 genetic sequences were published5 and laboratory testing capacity was increased in all three locations, although expansion of the diagnostic capacity to university and large private laboratories in Japan is still ongoing. In Hong Kong, initially, only pneumonia patients without a microbiological diagnosis were tested, but surveillance has been broadened to include all inpatients with pneumonia and a purposively sampled proportion of outpatients and emergency attendees totalling about 1500 per day (Leung GM, unpublished). Japan's testing strategy has also evolved with diagnostic tests now offered to all suspected cases irrespective of their travel history; however, there are reports of cases that should have been tested but were not.",,"Legido-Quigley, Helena; Asgari, Nima; Teo, Yik Ying; Leung, Gabriel M.; Oshitani, Hitoshi; Fukuda, Keiji; Cook, Alex R.; Hsu, Li Yang; Shibuya, Kenji; Heymann, David",The Lancet,2980700437,#5422,
,CZI,SARS-CoV-2 is an appropriate name for the new coronavirus,10.1016/S0140-6736(20)30557-2,,,,"We have read with great interest the Correspondence by Shibo Jiang and colleagues,1 in which they propose a name change for the newly emerged coronavirus,2 which was recently designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses.3 The authors argued that the use of SARS in the virus name could confuse the public about the disease that it causes; in addition, they noted that the name SARS-CoV-2 is not consistent with the disease name chosen by WHO, coronavirus disease 2019. The authors also indicated that scientifically, SARS-CoV-2 is naturally occurring and different from other SARS-like or SARS-related coronaviruses that are mainly characterised by their genome sequences. Furthermore, given the probability of future attenuation of this virus to a low-pathogenic form, the authors predict that the use of the name SARS-CoV-2 might have adverse effects, both socially and economically. On these grounds, the authors suggest that the name of the new virus is changed to human coronavirus 2019 (HCoV-19). Although these concerns and suggestions are appreciated, we feel that the adoption of SARS-CoV-2 by the Coronavirus Study Group was appropriate. To facilitate good practice and scientific exchange, the International Committee on Taxonomy of Viruses has established standardised formats for classifying viruses. Under these rules, a newly emerged virus is normally assigned to a species based on phylogeny and taxonomy.4 Through DivErsity pArtitioning by hieRarchical Clustering-based analyses,5 the newly emerged coronavirus was deemed not sufficiently novel but is a sister virus to SARS-CoV, the primary viral isolate defining the species. The SARS-CoV species includes viruses such as SARS-CoV, SARS-CoV_PC4-227, and SARSr-CoV-btKY72. SARS-CoV-2 is the newest member of this viral species. The use of SARS in naming SARS-CoV-2 does not derive from the name of the SARS disease but is a natural extension of the taxonomic practice for viruses in the SARS species. The use of SARS for viruses in this species mainly refers to their taxonomic relationship to the founding virus of this species, SARS-CoV. In other words, viruses in this species can be named SARS regardless of whether or not they cause SARS-like diseases.",,"Wu, Yuntao; Ho, Wenzhe; Huang, Yaowei; Jin, Dong-Yan; Li, Shiyue; Liu, Shan-Lu; Liu, Xuefeng; Qiu, Jianming; Sang, Yongming; Wang, Qiuhong; Yuen, Kwok-Yung; Zheng, Zhi-Ming",The Lancet,2047323912,#5425,
,CZI,Coronavirus spreads,10.1016/S0262-4079(20)30188-3,,,,"The deadly virus that emerged in Wuhan, China, may be much more contagious than initially thought. Jessica Hamzelou reports",2020,"Hamzelou, Jessica",New Scientist,3002306895,#145,
,CZI,Viruses from animals,10.1016/S0262-4079(20)30236-0,,,,Infections that cross over from other species are a deadly problem,2020,"Le Page, Michael",New Scientist,3003282835,#500,
,CZI,How bad will it get?,10.1016/S0262-4079(20)30278-5,,,,"While the coronavirus death rate may be lower than some estimates, case numbers may be far higher, reports Debora MacKenzie",2020,"MacKenzie, Debora",New Scientist,3005843255,#944,
,CZI,Wuhan-like virus discovered seven years ago,10.1016/S0262-4079(20)30281-5,,,,,2020,"MacKenzie, Debora",New Scientist,3006474128,#943,
,CZI,Is it super-spreading?,10.1016/S0262-4079(20)30375-4,,,,"If the covid-19 virus is transmitted largely by superspreaders, it might not go pandemic, reports Debora MacKenzie",2020,"MacKenzie, Debora",New Scientist,2078552808,#1553,
,CZI,Drug trials under way,10.1016/S0262-4079(20)30376-6,,,,"We'll soon know if covid-19 can be treated with drugs developed for HIV and Ebola, reports Alice Klein",2020,"Klein, Alice",New Scientist,2888181989,#1605,
,CZI,Will heat kill the coronavirus?,10.1016/S0262-4079(20)30377-8,,,,"We don't know if changing seasons will help stem the outbreak, says Michael Le Page",2020,"Le Page, Michael",New Scientist,2989729408,#1596,
,CZI,China uses mass surveillance tech to fight spread of coronavirus,10.1016/S0262-4079(20)30378-X,,,,,2020,"Lu, Donna",New Scientist,2792118424,#1808,
,CZI,Calculating virus spread,10.1016/S0262-4079(20)30402-4,,,,"Getting a full picture of the coronavirus outbreak is extremely difficult. Maths can help plug some of the gaps, says Adam Kucharski",2020,"Kucharski, Adam",New Scientist,3006474128,#1600,
,CZI,Covid-19 spreads in US,10.1016/S0262-4079(20)30472-3,,,,Multiple outbreaks worldwide have led to countries stepping up their responses. By Debora MacKenzie and Press Association,2020,"MacKenzie, Debora; Association, Press",New Scientist,2113767588,#4881,
,CZI,How well prepared are we?,10.1016/S0262-4079(20)30473-5,,,,"Covid-19 is rapidly spreading around the world during a period when many healthcare systems are already under pressure, reports Debora MacKenzie",2020,"MacKenzie, Debora",New Scientist,753948547,#4880,
,CZI,"We were warned, so why couldn't we prevent it?",10.1016/S0262-4079(20)30476-0,,,,"SARS and MERS gave us ample warning of the risk of new coronaviruses, but we failed to set up sufficient defences, reports Debora MacKenzie",2020,"MacKenzie, Debora",New Scientist,1983232861,#4879,
,CZI,World braces for economic impact,10.1016/S0262-4079(20)30477-2,,,,"The repercussions for businesses, workers and supply chains could be severe",2020,"Vaughan, Adam",New Scientist,3005609763,#5499,
,CZI,A correlation study ofCT and clinical features of different clinical types of 2019 novel coronavirus pneumonia,10.1016/s0618-8278(19)30533-x,,,,"Objective To investigate the CT and clinical features of 2019 novel coronavirus (NCP) pneumonia. Methods Chest CT and clinical data of confirmed 103 patients with 2019 novel coronavirus pneumonia in January 2020, retrospectively. According to diagnosis and treatment of NCP infected pneumonia (trial version 5), all the patients were classified into mild( n =58), severe ( n =36) and very severe ( n =9) type, and their clinical findings, laboratory examination and CT finding were analyzed. CT features included lesions’ distribution, location, size, shape, edge, number, density, percentage of pneumonia lesions of the whole lung and extra-pulmonary manifestations. The CT features of different clinical subtypes were compared using χ 2 test or Fisher's exact probability. Comparisons between the percentage of pneumonic lesions to total lung volume were computed by using analysis of variance (normal distribution) or Kruskal-Wallis rank sum test (non-normal distribution). Results In terms of clinical manifestations, the patients with severe NCP were more common in elderly men, with a median age of 65 years. Fever was the first symptom in 49 (84%) of 58 patients with NCP, and fever was the first symptom in both severe and critical NCP patients. The incidence of cough in severe (25 / 36, 69%) and critical (6 /9, 67%) NCP patients was higher than that in general (20 /58, 34%). All critical patients have dyspnea. In terms of CT findings, common NCP showed double lung (40/58,71%) multiple (40 / 58,69%) ground glass (31/58,52%) or mixed (25 / 58,43%) lesions (56 / 58,97%); severe and critical NCP showed double lung lesions, heavy NCP mainly showed multiple (34 / 36,96%) patches (33 / 36,92%) mixed density lesions (26 / 36,72%); 9 severe NCP lesions were more than 3 cm Mixed density lesions. The percentage of pneumonia focus in the whole lung volume: the common type (12.5% ± 6.1%) was significantly lower than the severe type (25.9% ± 10.7%) and the critical type (47.2% ± 19.2%) NCP, the difference was statistically significant ( P values were < 0.001 and 0.002 respectively), and the severe type NCP was also significantly lower than the critical type ( P = 0.032). Conclusions CT and clinical features of different clinical types of NCP pneumonia are different. Chest CT findings have unique characteristic, which can not only make early diagnosis, but also evaluate its clinical course and severity.",2020,"HUANG, Lu; HAN, Rui; YU, Pengxin; WANG, Shaokang; XIA, Liming",Chinese Journal of Radiology,2937473538,#2257,
,CZI,Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China,10.1016/S1470-2045(20)30096-6,,,,,2020,"Liang, Wenhua; Guan, Weijie; Chen, Ruchong; Wang, Wei; Li, Jianfu; Xu, Ke; Li, Caichen; Ai, Qing; Lu, Weixiang; Liang, Hengrui; Li, Shiyue; He, Jianxing",The Lancet Oncology,3006355661,#951,
,CZI,Risk of COVID-19 for patients with cancer,10.1016/S1470-2045(20)30149-2,,,,"The authors concluded by use of epidemiological statistics that because the proportion of patients with cancer histories was higher in a cohort with COVID-19 than in the population in China, patients with cancer were more likely to develop COVID-19. They found 18 COVID-19 patients with cancer histories among 1590 COVID-19 patients from 575 hospitals in 31 provincial regions. Of these 16 patients (two of the 18 patients had unknown treatment status), only four had undergone surgery or chemotherapy within the previous month; 12 had recovered from initial cancer treatments (eg, surgery or chemotherapy) and had no obvious immunosuppression. We therefore do not think the COVID-19 infections in the 12 survivors of previous cancers were associated with their cancers. COVID-19 is a highly contagious infection to which everyone, to our knowledge, is susceptible; the most important morbidity factor is exposure to an infection source.2 Furthermore, although the authors indicate that patients with cancer had worse outcomes from COVID-19, they also reported the median age of these patients (63·1 years) to be significantly higher than for those without cancer (48·7 years), suggesting that older age is associated with worse COVID-19 outcomes",,"Wang, Hanping; Zhang, Li",The Lancet Oncology,2600570919,#3482,
,CZI,Risk of COVID-19 for cancer patients,10.1016/S1470-2045(20)30150-9,,,,"We read the excellent Comment by Wenhua Liang and colleagues1 in The Lancet Oncology with great interest. Of 1590 cases with confirmed coronavirus disease 2019 (COVID-19), 18 patients had a history of cancer. The authors concluded that patients with cancer had a higher risk of COVID-19 and with a poorer prognosis than those without cancer. First, the data in the Comment by Liang and colleagues1 showed a higher percentage of patients with cancer in the COVID-19 cohort than in the overall population. However, this observation is not sufficient to conclude that patients with cancer had a higher risk of COVID-19. The incidence of COVID-19 in patients with cancer would be more informative in assessing whether or not patients with cancer have an increased risk of COVID-19. Second, we reviewed the cancer history of the 18 individuals discussed in Liang and colleagues' Comment.1 We are concerned that such a small sample size with a large amount of heterogeneity, presenting as various cancer types with different biological behaviours, highly variable disease courses (from 0–16 years), and diverse treatment strategies, might be filled with contingency and thus not ideally representative of the whole population with cancer. Notably, half of the patients with cancer had a disease course of more than 4 years, indicating that a substantial proportion of these patients might be clinically cured.",,"Xia, Yang; Jin, Rui; Zhao, Jing; Li, Wen; Shen, Huahao",The Lancet Oncology,2947157398,#3481,
,CZI,Game consumption and the 2019 novel coronavirus,10.1016/S1473-3099(20)30063-3,,,,,,"Li, Jie; Li, Jun; Xie, Xiaoru; Cai, Xiaomei; Huang, Jian; Tian, Xuemei; Zhu, Hong",The Lancet Infectious Diseases,3005031775,#515,
,CZI,The first 2019 novel coronavirus case in Nepal,10.1016/S1473-3099(20)30067-0,,,,,2020,"Bastola, Anup; Sah, Ranjit; Rodriguez-Morales, Alfonso J.; Lal, Bibek Kumar; Jha, Runa; Ojha, Hemant Chanda; Shrestha, Bikesh; Chu, Daniel K. W.; Poon, Leo L. M.; Costello, Anthony; Morita, Kouichi; Pandey, Basu Dev",The Lancet Infectious Diseases,3004634239,#628,
,CZI,Pandemic potential of 2019-nCoV,10.1016/S1473-3099(20)30068-2,,,,,2020,"Thompson, Robin",The Lancet Infectious Diseases,3004907789,#514,
,CZI,Correction to Lancet Infect Dis 2019; 20: 275–76,10.1016/S1473-3099(20)30071-2,,,,,2020,,The Lancet Infectious Diseases,,#2468,
,CZI,Challenges of coronavirus disease 2019,10.1016/S1473-3099(20)30072-4,,,,,,"The Lancet Infectious, Diseases",The Lancet Infectious Diseases,2981418129,#1103,
,CZI,Outbreak of coronavirus disease 2019,10.1016/S1473-3099(20)30076-1,,,,,,"Burki, Talha",The Lancet Infectious Diseases,3006609801,#1163,
,CZI,"Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study",10.1016/S1473-3099(20)30086-4,,,,"Summary Background A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. We aimed to describe the CT findings across different timepoints throughout the disease course. Methods Patients with COVID-19 pneumonia (confirmed by next-generation sequencing or RT-PCR) who were admitted to one of two hospitals in Wuhan and who underwent serial chest CT scans were retrospectively enrolled. Patients were grouped on the basis of the interval between symptom onset and the first CT scan: group 1 (subclinical patients; scans done before symptom onset), group 2 (scans done ≤1 week after symptom onset), group 3 (>1 week to 2 weeks), and group 4 (>2 weeks to 3 weeks). Imaging features and their distribution were analysed and compared across the four groups. Findings 81 patients admitted to hospital between Dec 20, 2019, and Jan 23, 2020, were retrospectively enrolled. The cohort included 42 (52%) men and 39 (48%) women, and the mean age was 49·5 years (SD 11·0). The mean number of involved lung segments was 10·5 (SD 6·4) overall, 2·8 (3·3) in group 1, 11·1 (5·4) in group 2, 13·0 (5·7) in group 3, and 12·1 (5·9) in group 4. The predominant pattern of abnormality observed was bilateral (64 [79%] patients), peripheral (44 [54%]), ill-defined (66 [81%]), and ground-glass opacification (53 [65%]), mainly involving the right lower lobes (225 [27%] of 849 affected segments). In group 1 (n=15), the predominant pattern was unilateral (nine [60%]) and multifocal (eight [53%]) ground-glass opacities (14 [93%]). Lesions quickly evolved to bilateral (19 [90%]), diffuse (11 [52%]) ground-glass opacity predominance (17 [81%]) in group 2 (n=21). Thereafter, the prevalence of ground-glass opacities continued to decrease (17 [57%] of 30 patients in group 3, and five [33%] of 15 in group 4), and consolidation and mixed patterns became more frequent (12 [40%] in group 3, eight [53%] in group 4). Interpretation COVID-19 pneumonia manifests with chest CT imaging abnormalities, even in asymptomatic patients, with rapid evolution from focal unilateral to diffuse bilateral ground-glass opacities that progressed to or co-existed with consolidations within 1–3 weeks. Combining assessment of imaging features with clinical and laboratory findings could facilitate early diagnosis of COVID-19 pneumonia. Funding None.",2020,"Shi, Heshui; Han, Xiaoyu; Jiang, Nanchuan; Cao, Yukun; Alwalid, Osamah; Gu, Jin; Fan, Yanqing; Zheng, Chuansheng",The Lancet Infectious Diseases,3001118548,#1769,
,CZI,Initiation of a new infection control system for the COVID-19 outbreak,10.1016/S1473-3099(20)30110-9,,,,,,"Chen, Xuejiao; Tian, Junzhang; Li, Guanming; Li, Guowei",The Lancet Infectious Diseases,2914278034,#1195,
,CZI,The first Vietnamese case of COVID-19 acquired from China,10.1016/S1473-3099(20)30111-0,,,,,2020,"Van Cuong, Le; Giang, Hoang Thi Nam; Linh, Le Khac; Shah, Jaffer; Van Sy, Le; Hung, Trinh Huu; Reda, Abdullah; Truong, Luong Ngoc; Tien, Do Xuan; Huy, Nguyen Tien",The Lancet Infectious Diseases,2198156900,#1193,
,CZI,Viral load of SARS-CoV-2 in clinical samples,10.1016/S1473-3099(20)30113-4,,,,,2020,"Pan, Yang; Zhang, Daitao; Yang, Peng; Poon, Leo L. M.; Wang, Quanyi",The Lancet Infectious Diseases,2041451020,#1791,
,CZI,Asymptomatic cases in a family cluster with SARS-CoV-2 infection,10.1016/S1473-3099(20)30114-6,,,,,2020,"Pan, Xingfei; Chen, Dexiong; Xia, Yong; Wu, Xinwei; Li, Tangsheng; Ou, Xueting; Zhou, Liyang; Liu, Jing",The Lancet Infectious Diseases,3005688502,#1275,
,CZI,Open access epidemiological data from the COVID-19 outbreak,10.1016/S1473-3099(20)30119-5,,32087115,,,2020,"Xu, Bo; Kraemer, Moritz U. G.; Open, Covid-Data Curation Group",Lancet Infect Dis,3005879071,#1450,
,CZI,An interactive web-based dashboard to track COVID-19 in real time,10.1016/S1473-3099(20)30120-1,,,,,2020,"Dong, Ensheng; Du, Hongru; Gardner, Lauren",The Lancet Infectious Diseases,167054977,#1317,
,CZI,Correction to Lancet Infect Dis 2020; published online Feb 18. https://doi.org/10.1016/S1473-3099(20)30111-0,10.1016/S1473-3099(20)30128-6,,,,"Cuong LV, Giang HTN, Linh LC, et al. The first Vietnamese case of COVID-19 acquired from China. Lancet Infectious Diseases 2020; published online Feb 18. https://doi.org/10.1016/S1473-3099(20)30111-0—In this Letter, parts A and B in the figure were labelled the wrong way around. This correction has been made to the online version as of Feb 24, 2020, and will be made to the printed version.",2020,,The Lancet Infectious Diseases,2604173926,#2034,
,CZI,Can we contain the COVID-19 outbreak with the same measures as for SARS?,10.1016/S1473-3099(20)30129-8,,,,"The severe acute respiratory syndrome (SARS) outbreak in 2003 resulted in more than 8000 cases and 800 deaths. SARS was eventually contained by means of syndromic surveillance, prompt isolation of patients, strict enforcement of quarantine of all contacts, and in some areas top-down enforcement of community quarantine. By interrupting all human-to-human transmission, SARS was effectively eradicated. By contrast, by Feb 28, 2020, within a matter of 2 months since the beginning of the outbreak of coronavirus disease 2019 (COVID-19), more than 82?000 confirmed cases of COVID-19 have been reported with more than 2800 deaths. Although there are striking similarities between SARS and COVID-19, the differences in the virus characteristics will ultimately determine whether the same measures for SARS will also be successful for COVID-19. COVID-19 differs from SARS in terms of infectious period, transmissibility, clinical severity, and extent of community spread. Even if traditional public health measures are not able to fully contain the outbreak of COVID-19, they will still be effective in reducing peak incidence and global deaths. Exportations to other countries need not result in rapid large-scale outbreaks, if countries have the political will to rapidly implement countermeasures.",,"Wilder-Smith, Annelies; Chiew, Calvin J.; Lee, Vernon J.",The Lancet Infectious Diseases,3006642361,#4409,
,CZI,COVID-19: combining antiviral and anti-inflammatory treatments,10.1016/S1473-3099(20)30132-8,,,,"Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are characterised by an overexuberant inflammatory response and, for SARS, viral load is not correlated with the worsening of symptoms. In our previous Correspondence to The Lancet, we described how BenevolentAI's proprietary artificial intelligence (AI)-derived knowledge graph, queried by a suite of algorithms, enabled identification of a target and a potential therapeutic against SARS coronavirus 2 (SARS-CoV-2; the causative organism in COVID-19). We identified a group of approved drugs that could inhibit clathrin-mediated endocytosis and thereby inhibit viral infection of cells (appendix). The drug targets are members of the numb-associated kinase (NAK) family—including AAK1 and GAK—the inhibition of which has been shown to reduce viral infection in vitro. Baricitinib was identified as a NAK inhibitor, with a particularly high affinity for AAK1, a pivotal regulator of clathrin-mediated endocytosis. We suggested that this drug could be of use in countering SARS-CoV-2 infections, subject to appropriate clinical testing.",,"Stebbing, Justin; Phelan, Anne; Griffin, Ivan; Tucker, Catherine; Oechsle, Olly; Smith, Dan; Richardson, Peter",The Lancet Infectious Diseases,2340158383,#2700,
,CZI,COVID-19 pneumonia: what has CT taught us?,10.1016/S1473-3099(20)30134-1,,,,,2020,"Lee, Elaine Y. P.; Ng, Ming-Yen; Khong, Pek-Lan",The Lancet Infectious Diseases,2009186097,#1818,
,CZI,Convalescent plasma as a potential therapy for COVID-19,10.1016/S1473-3099(20)30141-9,,,,,2020,"Chen, Long; Xiong, Jing; Bao, Lei; Shi, Yuan",The Lancet Infectious Diseases,2614362308,#2668,
,CZI,"A family cluster of SARS-CoV-2 infection involving 11 patients in Nanjing, China",10.1016/S1473-3099(20)30147-X,,,,,2020,"Huang, Rui; Xia, Juan; Chen, Yuxin; Shan, Chun; Wu, Chao",The Lancet Infectious Diseases,3006355661,#2836,
,CZI,Taking the right measures to control COVID-19,10.1016/S1473-3099(20)30152-3,,,,"First, although COVID-19 is spread by the airborne route, air disinfection of cities and communities is not known to be effective for disease control and needs to be stopped. The widespread practice of spraying disinfectant and alcohol in the sky, on roads, vehicles, and personnel has no value; moreover, large quantities of alcohol and disinfectant are potentially harmful to humans and should be avoided.3 , 4 Second, in the use of personal protective equipment, we should try to distinguish different risk factors, adopt different epidemic prevention measures, and reduce the waste of personal protective equipment, as these resources are already in short supply. Although surgical masks are in widespread use by the general population, there is no evidence that these masks prevent the acquisition of COVID-19, although they might slightly reduce the spread from an infected patient. High-filtration masks such as N95 masks and protective clothing (goggles and gowns) should be used in hospitals where health-care workers are in direct contact with infected patients.5 Third, the practice of blocking traffic and lockdown of villages is of no value for the prevention and control of COVID-19. Since the outbreak of COVID-19, some countries have suspended flights to and from China, and prevented Chinese people from travelling to their countries; both of these actions violate WHO International Health Regulations.6 Similarly, in community prevention and control of the disease, the measures taken by individual villages and communities to seal off roads are of no value.7 Such measures could result in civil unrest and reduce compliance with infection prevention and control advice. Fourth, public health education must be based on scientific evidence to reduce the anxiety and distress caused by misinformation. In particular, epidemiological findings need to be reported in a timely and objective manner so that they can be accurately assessed and interpreted. The risk of transmission with brief contact (less than 15 min face-to-face contact) or infection onset after 14 days of exposure to a known infected person (the estimated maximum incubation period) is low and should not be over-exaggerated. Misinformation spreads panic among the general population and is not conducive to implementation of epidemic control measures.8 Fifth, WHO has made it clear that there are currently no known effective treatments for COVID-19 and does not recommend the use of antiviral drugs, antibiotics, glucocorticoids, or traditional Chinese medicine. Despite this, there have been reports of the use of oseltamivir, lopinavir/ritonavir, prednisone, antibiotics, and traditional Chinese medicine for the treatment of patients with COVID-19.9 Care should be taken to not give patients drugs of unknown efficacy, which might be detrimental to critically ill patients with COVID-19; clinical trials are urgently required in this context.10 Likewise, the development of a vaccine is an urgent public health priority.",,"Xiao, Yonghong; Torok, Mili Estee",The Lancet Infectious Diseases,3006007867,#4397,
,CZI,Guidelines for pregnant women with suspected SARS-CoV-2 infection,10.1016/S1473-3099(20)30157-2,,,,"Coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) can cause severe adverse pregnancy outcomes, such as miscarriage, premature delivery, intrauterine growth restriction, and maternal death.1 , 2 Vertical transmission of the virus responsible for 2019 novel coronavirus disease (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has not yet been detected, whereas perinatal transmission has been suspected in one case.3 Consequences of infection with SARS-CoV-2 for pregnancies are uncertain, with no evidence so far of severe outcomes for mothers and infants; however, the possibility should be considered.4 The recent experience with Zika virus suggests that when a new pathogen emerges, the health-care community should be prepared for the worst-case scenario.5 Therefore, recommendations for management of pregnant women at risk of SARS-CoV-2 infection are urgently needed. To this end, we propose a detailed management algorithm for health-care providers (appendix).",,"Favre, Guillaume; Pomar, Léo; Qi, Xiaolong; Nielsen-Saines, Karin; Musso, Didier; Baud, David",The Lancet Infectious Diseases,1940662020,#3484,
,CZI,Covert COVID-19 and false-positive dengue serology in Singapore,10.1016/S1473-3099(20)30158-4,,,,"Dengue and coronavirus disease 2019 (COVID-19) are difficult to distinguish because they have shared clinical and laboratory features.1 , 2 We describe two patients in Singapore with false-positive results from rapid serological testing for dengue, who were later confirmed to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative virus of COVID-19. The first case is a 57-year-old man with no relevant past medical, travel, or contact history, who presented to a regional hospital on Feb 9, 2020, with 3 days of fever and cough. He had thrombocytopenia (platelet count 140 × 109/mL) and a normal chest radiograph. He was discharged after a negative rapid test for dengue NS1, IgM, and IgG (SD Bioline Dengue Duo Kit; Abbott, South Korea). He returned to a public primary health-care clinic with persistent fever, worsening thrombocytopenia (89 × 109/mL), and new onset lymphopenia (0·43 × 109/mL). A repeat dengue rapid test was positive for dengue IgM and IgG (Dengue Combo; Wells Bio, South Korea). He was referred to hospital for dengue with worsening cough and dyspnoea. A chest radiograph led to testing for SARS-CoV-2 by RT-PCR (in-house laboratory-developed test detecting the N and ORF1ab genes) from a nasopharyngeal swab, which returned positive. The original seropositive sample and additional urine and blood samples tested negative for dengue, chikungunya, and Zika viruses by RT-PCR,3 , 4 , 5 and a repeat dengue rapid test (SD Bioline) was also negative. Thus, the initial dengue seroconversion result was deemed a false positive.",,"Yan, Gabriel; Lee, Chun Kiat; Lam, Lawrence T. M.; Yan, Benedict; Chua, Ying Xian; Lim, Anita Y. N.; Phang, Kee Fong; Kew, Guan Sen; Teng, Hazel; Ngai, Chin Hong; Lin, Li; Foo, Rui Min; Pada, Surinder; Ng, Lee Ching; Tambyah, Paul Anantharajah",The Lancet Infectious Diseases,2810796836,#4251,
,CZI,Outbreak investigation for COVID-19 in northern Vietnam,10.1016/S1473-3099(20)30159-6,,,,"Two Vietnamese adults returned to their home province of Vinh Phuc in northern Vietnam on Jan 17, 2020, from Wuhan, China, where they had been living since Nov 15, 2019, for a business trip. They presented with mild respiratory symptoms to their local health facilities at 4 days and 8 days, respectively, after arrival in Vinh Phuc. Both individuals were initially placed into respiratory isolation in hospital. Case 1 tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative organism of coronavirus disease 2019 (COVID-19), on Jan 30, 2020, and remained in isolation until recovery. Case 2 was discharged from isolation in hospital after having one negative test result on Jan 28 (11 days after returning from Wuhan). Following discharge, the patient attended a family social function. 2 days later, she was readmitted after a second nasal swab for SARS-CoV-2 taken during her time in hospital was reported as positive. Screening of 79 individuals who had been in contact with these two patients (namely, family members in the same household and anyone who had been within 2 m of them) was initiated on Jan 31. Six individuals from the same work team, who had also travelled from Wuhan on Jan 17, were isolated, and four of them tested positive for SARS-CoV-2 (cases 3, 4, and 8 in Vinh Phuc, and one case from another province). Five secondary cases were diagnosed within the social network of case 2. These included three household members (cases 6, 7, and 11) and two people who had attended the social function (cases 5 and 9; appendix p 1). Four of these individuals reported mild respiratory symptoms; the remaining patient was asymptomatic (case 7) at the time of diagnosis.",,"Thanh, Hai Nguyen; Van, Truong Nguyen; Thu, Huong Ngo Thi; Van, Binh Nghiem; Thanh, Binh Doan; Thu, Ha Phung Thi; Kieu, Anh Nguyen Thi; Viet, Nhung Nguyen; Marks, Guy B.; Fox, Greg J.; Nguyen, Thu-Anh",The Lancet Infectious Diseases,2904779985,#4012,
,CZI,"Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial",10.1016/S2213-2600(19)30417-5,,,,"BackgroundThere is no proven specific pharmacological treatment for patients with the acute respiratory distress syndrome (ARDS). The efficacy of corticosteroids in ARDS remains controversial. We aimed to assess the effects of dexamethasone in ARDS, which might change pulmonary and systemic inflammation and result in a decrease in duration of mechanical ventilation and mortality.",,"Villar, Jesús; Ferrando, Carlos; Martínez, Domingo; Ambrós, Alfonso; Muñoz, Tomás; Soler, Juan A.; Aguilar, Gerardo; Alba, Francisco; González-Higueras, Elena; Conesa, Luís A.; Martín-Rodríguez, Carmen; Díaz-Domínguez, Francisco J.; Serna-Grande, Pablo; Rivas, Rosana; Ferreres, José; Belda, Javier; Capilla, Lucía; Tallet, Alec; Añón, José M.; Fernández, Rosa L.; González-Martín, Jesús M.; Álvarez, Julián; Asensio, María J.; Blanco, Jesús; Blasco, Marisa; Cachafeiro, Lucia; del Campo, Rafael; Carbonell, José A.; Carbonell, Nieves; Cariñena, Agustín; Carriedo, Demetrio; Chico, Mario; Corpas, Ruth; Cuervo, Javier; Domínguez-Antelo, Cristina; Fernández, Lorena; Gamboa, Eneritz; González-Luengo, Raúl I.; Ortiz Díaz-Miguel, Ramón; Pérez-González, Raquel; Prieto, Ana M.; Prieto, Isidro; Rojas-Viguera, Leticia; Romera, Miguel A.; Sánchez-Ballesteros, Jesús; Segura, José M.; Serrano, Ainhoa; Solano, Rosario; Soro, Marina",The Lancet Respiratory Medicine,3004626187,#510,
,CZI,Coronavirus in China,10.1016/S2213-2600(20)30056-4,,,,"On Dec 31, 2019, China alerted WHO to several cases of pneumonia associated with an unknown virus. The cases were concentrated in Wuhan City, in Hubei Province in central China, home to 11 million people. By Jan 7, 2020, there was confirmation that a new type of coronavirus had emerged. It was temporarily named 2019-nCoV. It is the seventh identified coronavirus that can cause diseases of the respiratory tract in humans. On Jan 9, there was the first reported death from 2019-nCoV—a 61-year-old man who had visited the now-closed Huanan Seafood Wholesale Market, where the virus is thought to have originated. As of Jan 30, 2020, 7736 confirmed cases of 2019-nCoV had been reported in China, with a further 12?167 suspected cases. There had been 1370 severe cases, and 170 deaths. A few dozen additional cases had been detected in 18 countries around the world, of which only seven cases had no history of travel in China.",,"Burki, Talha Khan",The Lancet Respiratory Medicine,3004220385,#201,
,CZI,Coronavirus epidemic: preparing for extracorporeal organ support in intensive care,10.1016/S2213-2600(20)30060-6,,,,,2020,"Ronco, Claudio; Navalesi, Paolo; Vincent, Jean Louis",The Lancet Respiratory Medicine,3004784537,#379,
,CZI,Australian Government releases face masks to protect against coronavirus,10.1016/S2213-2600(20)30064-3,,,,,2020,"Kirby, Tony",The Lancet Respiratory Medicine,3004752580,#512,
,CZI,Protecting health-care workers from subclinical coronavirus infection,10.1016/S2213-2600(20)30066-7,,,,,2020,"Chang, De; Xu, Huiwen; Rebaza, Andre; Sharma, Lokesh; Dela Cruz, Charles S.",The Lancet Respiratory Medicine,3005798348,#833,
,CZI,Toning down the 2019-nCoV media hype—and restoring hope,10.1016/S2213-2600(20)30070-9,,,,,2020,"Ippolito, Giuseppe; Hui, David S.; Ntoumi, Francine; Maeurer, Markus; Zumla, Alimuddin",The Lancet Respiratory Medicine,,#768,
,CZI,Therapeutic and triage strategies for 2019 novel coronavirus disease in fever clinics,10.1016/S2213-2600(20)30071-0,,,,,2020,"Zhang, Jinnong; Zhou, Luqian; Yang, Yuqiong; Peng, Wei; Wang, Wenjing; Chen, Xuelin",The Lancet Respiratory Medicine,3005678464,#832,
,CZI,Pathological findings of COVID-19 associated with acute respiratory distress syndrome,10.1016/S2213-2600(20)30076-X,,,,,2020,"Xu, Zhe; Shi, Lei; Wang, Yijin; Zhang, Jiyuan; Huang, Lei; Zhang, Chao; Liu, Shuhong; Zhao, Peng; Liu, Hongxia; Zhu, Li; Tai, Yanhong; Bai, Changqing; Gao, Tingting; Song, Jinwen; Xia, Peng; Dong, Jinghui; Zhao, Jingmin; Wang, Fu-Sheng",The Lancet Respiratory Medicine,2835497422,#1187,
,CZI,"Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study",10.1016/S2213-2600(20)30079-5,,,,"Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.",2020,"Yang, Xiaobo; Yu, Yuan; Xu, Jiqian; Shu, Huaqing; Xia, Jia'an; Liu, Hong; Wu, Yongran; Zhang, Lu; Yu, Zhui; Fang, Minghao; Yu, Ting; Wang, Yaxin; Pan, Shangwen; Zou, Xiaojing; Yuan, Shiying; Shang, You",The Lancet Respiratory Medicine,2109520345,#1733,
,CZI,Pandemic: examining readiness for infectious disease outbreaks,10.1016/S2213-2600(20)30082-5,,,,,2020,"Burki, Talha Khan",The Lancet Respiratory Medicine,1982319340,#1411,
,CZI,Staff safety during emergency airway management for COVID-19 in Hong Kong,10.1016/S2213-2600(20)30084-9,,,,,2020,"Cheung, Jonathan Chun-Hei; Ho, Lap Tin; Cheng, Justin Vincent; Cham, Esther Yin Kwan; Lam, Koon Ngai",The Lancet Respiratory Medicine,2774197594,#1857,
,CZI,Correction to Lancet Respir Med 2020; published online Feb 17. https://doi.org/10.1016/S2213-2600(20)30076-X,10.1016/S2213-2600(20)30085-0,,,,"Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; published online Feb 17. https://doi.org/10.1016/S2213-2600(20)30076-X—In this Case Report “by obtaining biopsy samples at autopsy” has been replace with “by postmortem biopsies” in paragraph 1, “microvascular” has been replaced with “microvesicular” in two incidences in paragraph 5, and “(B) Frequency of Th17 (CD4+ CCR6+CCR4+) subset” has been changed to “(B) Frequency of Th17 (CD4+ CCR6+) subset” on page 3 of the appendix. These corrections have been made to the online version as of Feb 25, 2020, and will be made to the printed version.",,,The Lancet Respiratory Medicine,2913752377,#2035,
,CZI,Respiratory support for patients with COVID-19 infection,10.1016/S2213-2600(20)30110-7,,,,"As of Feb 27, 2020, coronavirus disease 2019 (COVID-19) has affected 47 countries and territories around the world.1 Xiaobo Yang and colleagues2 described 52 of 710 patients with confirmed COVID-19 admitted to an intensive care unit (ICU) in Wuhan, China. 29 (56%) of 52 patients were given non-invasive ventilation at ICU admission, of whom 22 (76%) required further orotracheal intubation and invasive mechanical ventilation. The ICU mortality rate among those who required non-invasive ventilation was 23 (79%) of 29 and among those who required invasive mechanical ventilation was 19 (86%) of 22.2 Jonathan Chun-Hei Cheung and colleagues3 do not recommend use of a high-flow nasal cannula or non-invasive ventilation until the patient has viral clearance. Supporting the recommendation of the authors, I would like to add some points in relation to the use of high-flow nasal oxygen therapy and non-invasive ventilation in patients with COVID-19 infection: First, although exhaled air dispersion during high-flow nasal oxygen therapy and non-invasive ventilation via different interfaces is restricted, provided that there is a good mask interface fitting,4 not all hospitals around the world have access to such interfaces or enough personal-protective equipment of sufficiently high quality (ie, considered fit-tested particulate respirators, N95 or equivalent, or higher level of protection) for aerosol-generating procedures, and several hospitals do not have a negative pressure isolation room. Of 1688 health-care workers who have become infected with COVID-19, five (0·3%) have died;5 a sign of the vastly difficult working conditions for health-care workers.",,"Ñamendys-Silva, Silvio A.",The Lancet Respiratory Medicine,2379191983,#4491,
,CZI,Correction to Lancet Glob Health 2020; published online Feb 28. https://doi.org/10.1016/S2214-109X(20)30074-7,10.1016/S2214-109X(20)30083-8,,,,,2020,,The Lancet Global Health,2322586088,#4643,
,CZI,Timely mental health care for the 2019 novel coronavirus outbreak is urgently needed,10.1016/S2215-0366(20)30046-8,,,,"The 2019 novel coronavirus (2019-nCoV) pneumonia, believed to have originated in a wet market in Wuhan, Hubei province, China at the end of 2019, has gained intense attention nationwide and globally. To lower the risk of further disease transmission, the authority in Wuhan suspended public transport indefinitely from Jan 23, 2020; similar measures were adopted soon in many other cities in China. As of Jan 25, 2020, 30 Chinese provinces, municipalities, and autonomous regions covering over 1·3 billion people have initiated first-level responses to major public health emergencies. A range of measures has been urgently adopted,1,2 such as early identification and isolation of suspected and diagnosed cases, contact tracing and monitoring, collection of clinical data and biological samples from patients, dissemination of regional and national diagnostic criteria and expert treatment consensus, establishment of isolation units and hospitals, and prompt provision of medical supplies and external expert teams to Hubei province. The emergence of the 2019-nCoV pneumonia has parallels with the 2003 outbreak of severe acute respiratory syndrome (SARS), which was caused by another coronavirus that killed 349 of 5327 patients with confirmed infection in China.3 Although the diseases have different clinical presentations, the infectious cause, epidemiological features, fast transmission pattern, and insufficient preparedness of health authorities to address the outbreaks are similar. So far, mental health care for the patients and health professionals directly affected by the 2019-nCoV epidemic has been under-addressed, although the National Health Commission of China released the notification of basic principles for emergency psychological crisis interventions for the 2019-nCoV pneumonia on Jan 26, 2020. This notification contained a reference to mental health problems and interventions that occurred during the 2003 SARS outbreak, and mentioned that mental health care should be provided for patients with 2019-nCoV pneumonitis, close contacts, suspected cases who are isolated at home, patients in fever clinics, families and friends of affected people, health professionals caring for infected patients, and the public who are in need. To date, epidemiological data on the mental health problems and psychiatric morbidity of those suspected or diagnosed with the 2019-nCoV and their treating health professionals have not been available; therefore how best to respond to challenges during the outbreak is unknown. The observations of mental health consequences and measures taken during the 2003 SARS outbreak could help inform health authorities and the public to provide mental health interventions to those who are in need.",,"Xiang, Yu-Tao; Yang, Yuan; Li, Wen; Zhang, Ling; Zhang, Qinge; Cheung, Teris; Ng, Chee H.",The Lancet Psychiatry,3004804052,#207,
,CZI,"The mental health of medical workers in Wuhan, China dealing with the 2019 novel coronavirus",10.1016/S2215-0366(20)30047-X,,,,"The severe situation is causing mental health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger, and fear. These mental health problems not only affect the medical workers' attention, understanding, and decision making ability, which might hinder the fight against 2019-nCoV, but could also have a lasting effect on their overall wellbeing. Protecting the mental health of these medical workers is thus important for control of the epidemic and their own long-term health. The local government of Wuhan has implemented policies to address these mental health problems. Medical staff infected with 2019-nCoV while at work will be identified as having work-related injuries.As of Jan 25, 2020, 1230 medical workers have been sent from other provinces to Wuhan to care for patients who are infected and those with suspected infection, strengthen logistics support, and help reduce the pressure on health-care personnel.Most general hospitals in Wuhan have established a shift system to allow front-line medical workers to rest and to take turns in high-pressured roles. Online platforms with medical advice have been provided to share information on how to decrease the risk of transmission between the patients in medical settings, which aims to eventually reduce the pressure on medical workers.",,"Kang, Lijun; Li, Yi; Hu, Shaohua; Chen, Min; Yang, Can; Yang, Bing Xiang; Wang, Ying; Hu, Jianbo; Lai, Jianbo; Ma, Xiancang; Chen, Jun; Guan, Lili; Wang, Gaohua; Ma, Hong; Liu, Zhongchun",The Lancet Psychiatry,3005207746,#317,
,CZI,Psychological interventions for people affected by the COVID-19 epidemic,10.1016/S2215-0366(20)30073-0,,,,,2020,"Duan, Li; Zhu, Gang",The Lancet Psychiatry,2556905174,#1316,
,CZI,The neglected health of international migrant workers in the COVID-19 epidemic,10.1016/S2215-0366(20)30076-6,,,,,2020,"Liem, Andrian; Wang, Cheng; Wariyanti, Yosa; Latkin, Carl A.; Hall, Brian J.",The Lancet Psychiatry,3006304371,#1289,
,CZI,Online mental health services in China during the COVID-19 outbreak,10.1016/S2215-0366(20)30077-8,,,,,,"Liu, Shuai; Yang, Lulu; Zhang, Chenxi; Xiang, Yu-Tao; Liu, Zhongchun; Hu, Shaohua; Zhang, Bin",The Lancet Psychiatry,2020421786,#1189,
,CZI,Mental health care for medical staff in China during the COVID-19 outbreak,10.1016/S2215-0366(20)30078-X,,,,,,"Chen, Qiongni; Liang, Mining; Li, Yamin; Guo, Jincai; Fei, Dongxue; Wang, Ling; He, Li; Sheng, Caihua; Cai, Yiwen; Li, Xiaojuan; Wang, Jianjian; Zhang, Zhanzhou",The Lancet Psychiatry,2896665283,#1191,
,CZI,Mental health services for older adults in China during the COVID-19 outbreak,10.1016/S2215-0366(20)30079-1,,,,,2020,"Yang, Yuan; Li, Wen; Zhang, Qinge; Zhang, Ling; Cheung, Teris; Xiang, Yu-Tao",The Lancet Psychiatry,2129112369,#1188,
,CZI,A contingency plan for the management of the 2019 novel coronavirus outbreak in neonatal intensive care units,10.1016/S2352-4642(20)30040-7,,,,,,"Wang, Jianhui; Qi, Hongbo; Bao, Lei; Li, Fang; Shi, Yuan",The Lancet Child & Adolescent Health,3004657851,#517,
,CZI,Managing neonates with respiratory failure due to SARS-CoV-2 – Authors' reply,10.1016/S2352-4642(20)30072-9,,,,"Since December, 2019, a pneumonia of unknown cause, which has clinical manifestations similar to severe acute respiratory syndrome,1,2 originated in Wuhan, China, and has rapidly spread across China and to at least 23 countries. By Feb 5, 2020, the number of laboratory-confirmed cases had exceeded 20 000, with more than 400 deaths. About 100 children were affected, with the youngest being 30 h after birth. A novel virus named 2019 novel coronavirus (2019-nCoV) was considered to be the causative agent of this pneumonia. Neonates are thought to be susceptible to the virus because their immune system is not well developed, which is of great concern to neonatal medical service providers. Paediatricians and neonatologists belonging to the National Clinical Research Center for Child Health and Disorders and Pediatric Committee of Medical Association of Chinese People’s Liberation Army have contributed to the control efforts in China. We aim to elicit a contingency plan for the 2019-nCoV outbreak in neonatal intensive care units (NICUs), mainly focused on diagnostic and discharge criteria, treatment, prevention, and control strategies",2020,"Wang, Jianhui; Shi, Yuan",The Lancet Child & Adolescent Health,,#5270,
,CZI,Managing neonates with respiratory failure due to SARS-CoV-2,10.1016/S2352-4642(20)30073-0,,,,"In their Comment in The Lancet Child & Adolescent Health, Jianhui Wang and colleagues1 suggested a plan to handle neonates with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and outbreaks in neonatal intensive care units (NICUs). This is a timely reflection, given the public health problem represented by this infection and the need to anticipate any critical care issue, irrespective of patients' ages. However, the plan is incomplete or unsuitable in many points. We do not know anything about neonatal SARS-CoV-2 infections, and we must reasonably follow data from adult critical care. First, testing all NICU-admitted neonates for SARS-CoV-2 represents a wrongful use of resources. Neonatal respiratory failure can result from a wide range of causes, and testing everybody when other causes are reasonably suspected will divert laboratory resources from adult critical care. Tests should be done for infants from families infected by SARS-CoV-2 or exposed to other infected people, irrespective of their symptoms.",,"De Luca, Daniele",The Lancet Child & Adolescent Health,2002765492,#5421,
,CZI,Enteric involvement of coronaviruses: is faecal–oral transmission of SARS-CoV-2 possible?,10.1016/S2468-1253(20)30048-0,,,,,2020,"Yeo, Charleen; Kaushal, Sanghvi; Yeo, Danson",The Lancet Gastroenterology & Hepatology,,#1260,
,CZI,Liver injury in COVID-19: management and challenges,10.1016/S2468-1253(20)30057-1,,,,"SARS-CoV-2 shares 82% genome sequence similarity to SARS-CoV and 50% genome sequence homology to Middle East respiratory syndrome coronavirus (MERS-CoV)—all three coronaviruses are known to cause severe respiratory symptoms. Liver impairment has been reported in up to 60% of patients with SARS3 and has also been reported in patients infected with MERS-CoV.4 At least seven relatively large-scale case studies have reported the clinical features of patients with COVID-19.1 , 5 , 6 , 7 , 8 , 9 , 10 In this Comment, we assess how the liver is affected using the available case studies and data from The Fifth Medical Center of PLS General Hospital, Beijing, China. These data indicate that 2–11% of patients with COVID-19 had liver comorbidities and 14–53% cases reported abnormal levels of alanine aminotransferase and aspartate aminotransferase (AST) during disease progression (table). Patients with severe COVID-19 seem to have higher rates of liver dysfunction. In a study in The Lancet by Huang and colleagues,5 elevation of AST was observed in eight (62%) of 13 patients in the intensive care unit (ICU) compared with seven (25%) of 28 patients who did not require care in the ICU. Moreover, in a large cohort including 1099 patients from 552 hospitals in 31 provinces or provincial municipalities, more severe patients with disease had abnormal liver aminotransferase levels than did non-severe patients with disease.1 Furthermore, in another study,8 patients who had a diagnosis of COVID-19 confirmed by CT scan while in the subclinical phase (ie, before symptom onset) had significantly lower incidence of AST abnormality than did patients diagnosed after the onset of symptoms. Therefore, liver injury is more prevalent in severe cases than in mild cases of COVID-19.",,"Zhang, Chao; Shi, Lei; Wang, Fu-Sheng",The Lancet Gastroenterology & Hepatology,2398802113,#4278,
,CZI,Novel Coronavirus and Hospital Infection Prevention: Preparing for the Impromptu Speech,10.1017/ice.2020.55,,32122422,,,2020,"Bearman, Gonzalo; Pryor, Rachel; Albert, Heather; Brath, Lisa; Britton, Amy; Cooper, Kaila; Doll, Michelle; Godbout, Emily J.; Hemphill, Robin; Stevens, Michael P.",Infect Control Hosp Epidemiol,1736130314,#3457,
,CZI,Escalating infection control response to the rapidly evolving epidemiology of the Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 in Hong Kong,10.1017/ice.2020.58,,,,"Background:To describe the infection control preparedness for Coronavirus Disease (COVID-19) due to SARS-CoV-2 [previously known as 2019-novel coronavirus] in the first 42 days after announcement of a cluster of pneumonia in China, on 31 December 2019 (day 1) in Hong Kong.Methods:A bundle approach of active and enhanced laboratory surveillance, early airborne infection isolation, rapid molecular diagnostic testing, and contact tracing for healthcare workers (HCWs) with unprotected exposure in the hospitals was implemented. Epidemiological characteristics of confirmed cases, environmental and air samples were collected and analyzed.Results:From day 1 to day 42, forty-two (3.3%) of 1275 patients fulfilling active (n=29) and enhanced laboratory surveillance (n=13) confirmed to have SARS-CoV-2 infection. The number of locally acquired case significantly increased from 1 (7.7%) of 13 [day 22 to day 32] to 27 (93.1%) of 29 confirmed case [day 33 to day 42] (p<0.001). Twenty-eight patients (66.6%) came from 8 family clusters. Eleven (2.7%) of 413 HCWs caring these confirmed cases were found to have unprotected exposure requiring quarantine for 14 days. None of them was infected and nosocomial transmission of SARS-CoV-2 was not observed. Environmental surveillance performed in a patient with viral load of 3.3x106 copies/ml (pooled nasopharyngeal/ throat swab) and 5.9x106 copies/ml (saliva) respectively. SARS-CoV-2 revealed in 1 (7.7%) of 13 environmental samples, but not in 8 air samples collected at a distance of 10 cm from patient's chin with or without wearing a surgical mask.Conclusion:Appropriate hospital infection control measures could prevent nosocomial transmission of SARS-CoV-2.",,"Cheng, Vincent C. C.; Wong, Shuk-Ching; Chen, Jonathan H. K.; Yip, Cyril C. Y.; Chuang, Vivien W. M.; Tsang, Owen T. Y.; Sridhar, Siddharth; Chan, Jasper F. W.; Ho, Pak-Leung; Yuen, Kwok-Yung",Infection Control & Hospital Epidemiology,2040330380,#4656,
,CZI,Protecting Chinese Healthcare Workers While Combating the 2019 Novel Coronavirus,10.1017/ice.2020.60,,,,"Hospital-associated transmission is an important route of spreading the 2019 novel coronavirus (2019-nCoV) infection and pneumonia (Corona Virus Disease 2019, COVID-19) [1]. Healthcare workers (HCWs) are at high risk while combating COVID-19 at the very frontline, and nosocomial outbreaks among HCWs are not unusual in similar settings; the 2003 severe acute respiratory syndrome (SARS) outbreak led to over 966 HCW infections with 1.4% deaths in mainland China [2]. As of 11 February 2020, 3019 HCWs might have been infected with 2019-nCov in China, 1716 HCW cases were confirmed by nucleic acid testing[3], and at least 6 HCWs died, including the famous whistleblower Dr Li Wenliang. In view of this severe situation, we are recommending urgent interventions to help to protect HCWs.",,"Zhou, Pengcheng; Huang, Zebing; Xiao, Yinzong; Huang, Xun; Fan, Xue-Gong",Infection Control & Hospital Epidemiology,3004450134,#4651,
,CZI,The novel coronavirus (COVID-19) infection in Hangzhou: An experience to share,10.1017/ice.2020.62,,,,"Current situation in Hangzhou Hangzhou, the capital of Zhejiang province in China, was confronted with the pandemic of a novel coronavirus (COVID-19) that originated in Wuhan, Hubei province1 . According to the Health Commission of Zhejiang Province2 , six cases was first reported on January 19, 2020, and the cumulative cases reached 169 as of February 20, 2020. The situation in Hangzhou was once rather severe as it was once the top ranking city with respect to number of confirmed cases in Zhejiang province at the beginning of the epidemic. Since Hangzhou government took rigorous measures to contain the epidemic, positive trends have been seen. The daily number of newly confirmed cases has sharply decreased within the last week and there was only one confirmed case from February 17 to 20. Similarly, another point to be emphasized was that Hangzhou reported no deaths in its administrative region. We used a regression of log-incidence over time model3 ,which could provide a fitted trajectory for the actual daily incidence to verify the control effect. As show in Fig.1, the optimal splitting point, which was defined as the peak in number of daily new cases simulated by the model, occurred on January 25. That date was just about a week after launching the highest level of emergency public health alert and response in Hangzhou, which indicates that the prevention and control measures may be effective",,"Diao, MengYuan; Zhang, Sheng; Chen, Dechang; Hu, Wei",Infection Control & Hospital Epidemiology,3005847234,#4654,
,CZI,"The time-varying serial interval of the coronavirus disease (COVID-19) and its gender-specific difference: A data-driven analysis using public surveillance data in Hong Kong and Shenzhen, China from January 10 to February 15, 2020",10.1017/ice.2020.64,,,,"To the Editor. An outbreak of coronavirus disease (COVID-19), started in Wuhan, China in the end of 2019 [1], has now reached 40 countries and poses huge threat to global public health and economic [2]. Given the risk of human-to-human transmission, the serial interval (SI), which refers to the time interval from symptom onset of a primary case (i.e., infector) to that of a secondary case (i.e., infectee) [3], is the other essential quantity besides the basic reproduction number to drive the spreading speed. We examine the publicly available materials and collect the records of COVID-19 transmission events in two neighboring large cities, Hong Kong [4] and Shenzhen [5], in south China from January 10 to February 15, 2020 and extract the SI data. We identify 48 transmission events including 21 in Hong Kong and 27 in Shenzhen, among which 40 events contain the gender information of the primary cases. The last onset date of the primary cases among all collected transmission events is February 2, 2020.",,"Zhao, Shi; Cao, Peihua; Chong, Marc K. C.; Gao, Daozhou; Lou, Yijun; Ran, Jinjun; Wang, Kai; Wang, Weiming; Yang, Lin; He, Daihai; Wang, Maggie H.",Infection Control & Hospital Epidemiology,3006643024,#5426,
,CZI,Structure-based stabilization of non-native protein-protein interactions of coronavirus nucleocapsid proteins in antiviral drug design,10.1021/acs.jmedchem.9b01913,,,,"Structure-based stabilization of protein-protein interactions (PPIs) is a promising strategy for drug discovery. However, this approach has mainly focused on the stabilization of native PPIs and non-native PPIs have received little consideration. Here, we identified a non-native interaction interface on the 3D dimeric structure of the N-terminal domain of the MERS-CoV nucleocapsid protein (MERS-CoV N-NTD). The interface formed a conserved hydrophobic cavity suitable for targeted drug screening. By considering the hydrophobic complementarity during the virtual screening step, we identified 5-benzyloxygramine as a new N protein PPI orthosteric stabilizer that possesses both antiviral and N-NTD protein-stabilizing activity. X-ray crystallography and small-angle X-ray scattering showed that 5-benzyloxygramine stabilizes the N-NTD dimers through simultaneous hydrophobic interactions to both partners, resulting in abnormal N protein oligomerization that was further confirmed in the cell. This unique approach based on the identification and stabilization of non-native PPIs of N protein could be applied towards drug discovery against CoV diseases.",2020,"Lin, Shan-Meng; Lin, Shih-Chao; Hsu, Jia-Ning; Chang, Chung-ke; Chien, Ching-Ming; Wang, Yong-Sheng; Wu, Hung-Yi; Jeng, U. Ser; Kehn-Hall, Kylene; Hou, Ming-hon",Journal of Medicinal Chemistry,2035437208,#2598,
,CZI,Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential,10.1021/acsinfecdis.0c00052,,32125140,,"The recent outbreak of coronavirus disease 2019 (COVID-19) highlights an urgent need for therapeutics. Through a series of drug repurposing screening campaigns, niclosamide, an FDA-approved anthelminthic drug, was found to be effective against various viral infections with nanomolar to micromolar potency such as SARS-CoV, MERS-CoV, ZIKV, HCV and human adenovirus, indicating its potential as an antiviral agent. In this brief article, we summarize the broad antiviral activities of niclosamide and highlight its potential clinical use for treatment of COVID-19.",2020,"Xu, Jimin; Shi, Pei-Yong; Li, Hongmin; Zhou, Jia",ACS Infect Dis,2021189636,#3265,
,CZI,Pharma mobilizes to combat the coronavirus,10.1021/cen-09805-buscon4,,,,"The World Health Organization has declared the fast-moving coronavirus outbreak in China a “public health emergency of international concern,” a measure that can spur coordinated global efforts to combat it. With infections steadily rising, major drug companies are mobilizing to develop diagnostics, vaccines, and possible treatments for the virus, 2019-nCoV. According to WHO, as of Jan. 30 more than 7,800 people worldwide are confirmed to have been infected by the virus, and another 12,000-plus cases are suspected. Almost all of the cases are in China, where 170 people have died. Although smaller biotech firms were among the first to publicly respond to the outbreak, big pharma firms say they have been quietly working on tests and treatments for several weeks. Roche has sent the first commercial diagnostic to China, and Johnson & Johnson says it is using the same technologies deployed for the rapid development of an Ebola vaccine to(..)",2020,,C&EN Global Enterprise,2095772697,#807,
,CZI,China’s chemical industry shadowed by the coronavirus,10.1021/cen-09806-buscon1,,,,"With its escalating infections, city shutdowns, and nationwide transportation halts, the epidemic of the novel coronavirus is starting to strain China’s chemical industry. But experts see the impact as manageable and—they hope—short lived. By the afternoon of Feb. 6, more than 28,000 people in China were confirmed infected with the virus, almost 20,000 of them in the central Chinese province of Hubei. The death toll in China was 564, compared with 349 deaths in all of China from the severe acute respiratory syndrome (SARS) virus in 2003. The government shut down travel in and out of all cities in Hubei and extended the Lunar New Year holiday until Feb. 9 or 10 for most factories nationwide. Even if the epidemic is controlled in the next few months, frozen consumption, reduced factory output, and disturbed supply chains will cut 0.1 to 0.2 percentage points from global economic growth in 2020, according",2020,,C&EN Global Enterprise,,#1002,
,CZI,Coronavirus puts drug chemical industry on alert,10.1021/cen-09806-buscon2,,,,"Major drug companies have issued statements in recent days assuring the public that their inventories are adequate in the face of supply chain threats stemming from the novel coronavirus. Suppliers of active pharmaceutical ingredients (APIs) are also assuring customers that they are prepared for temporary interruption in the supply of key ingredients from firms in China, where the outbreak originated. API makers in Europe and the US warn, however, that supply disruptions could result from a protracted delay in restarting production at plants closed in recent weeks by the Chinese government or from prolonged transportation restrictions. James Bruno, president of the consulting firm Chemical and Pharmaceutical Solutions, says travel restrictions are already interrupting business with Chinese suppliers. “First of all, nobody is going to be able to get to China,” he says, “so all the audits are going to be canceled.” Bruno adds that the restrictions will prolong plant closures",2020,,C&EN Global Enterprise,3005804754,#809,
,CZI,Artificial intelligence finds drugs that could fight the new coronavirus,10.1021/cen-09806-scicon1,,,,"Two independent groups last week reported that they had used artificial intelligence in different ways to find possible treatments for the novel coronavirus, named 2019-nCoV. On Feb. 4, researchers from the AI drug discovery company BenevolentAI and Imperial College London reported that they had used AI software to find an already-approved drug that might limit the virus’s ability to infect people (Lancet 2020, DOI: 10.1016/S0140-6736(20)30304-4). On Feb. 6, Insilico Medicine announced that its AI algorithms had designed new molecules that could stop the virus from replicating in people’s bodies. The company says it submitted a paper to the bioRxiv server, but the preprint had not been posted there as of press time. BenevolentAI’s algorithms connect molecular structure data to biomedical information about relevant receptors and diseases to find potential drug targets. The group adapted its search to newly available information about 2019-nCoV and focused on the enzyme adaptor-associated protein kinase",2020,,C&EN Global Enterprise,3006492276,#808,
,CZI,Biotech start-ups hit by coronavirus work stoppages,10.1021/cen-09807-buscon3,,,,"s the outbreak of the new coronavirus, now officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to mushroom, the related work stoppages in China have put a spotlight on Western biotech companies’ dependence on Chinese contract research organizations (CROs). The situation has prompted some start-ups to rethink their contingency plans—particularly when it comes to chemistry services. Biotech firms had anticipated delays related to the Lunar New Year holidays, and so far outbreak-related travel restrictions have extended that work gap by only a week. But as the virus spreads—according to Chinese authorities, as of Feb. 13, more than 60,100 people had been infected and nearly 1,400 had died, most of them in China—some biotech firms that rely on China are becoming nervous about how long their projects could be on hold. Much attention is on WuXi AppTec, the largest Chinese CRO.",2020,,C&EN Global Enterprise,2548087481,#1174,
,CZI,"Sanofi, BARDA team for coronavirus vaccine",10.1021/cen-09808-buscon15,,,,"Sanofi Pasteur is working with the US Biomedical Advanced Research and Development Authority (BARDA) to develop a vaccine against the novel coronavirus, known as severe acute respiratory syndrome-CoV-2, which as of Feb. 20 had infected more than 75,000 people and killed more than 2,100. Sanofi will build on work on a vaccine against SARS, another coronavirus that circulated in the early 2000s. In December 2019, BARDA awarded the firm a $226 million contract to expand manufacturing capacity for use in a potential flu pandemic. Sanofi says the new vaccine will use the same technology.",2020,,C&EN Global Enterprise,2625213092,#1881,
,CZI,Structure of novel coronavirus’s spike protein solved,10.1021/cen-09808-scicon3,,,,"n a piece of research accomplished with astonishing speed, scientists from the University of Texas at Austin and the National Institutes of Health have released a cryo-electron microscopy (cryo-EM) structure of part of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that has infected tens of thousands of people and killed more than 2,000 since the end of December (Science 2020, DOI: 10.1126/science.abb2507). The part of the virus imaged, called the spike protein, helps the virus attach to and infect human cells, and the determination of its structure comes just weeks after the virus’s genome sequence was published. The breakthrough is a huge step toward developing a vaccine against the virus as well as treatments for COVID-19, the disease that it causes, the researchers say. UT Austin’s Jason McLellan and his colleagues, who have spent many years studying other coronaviruses, had already figured out how to use select",2020,,C&EN Global Enterprise,,#1880,
,CZI,Diagnosing COVID-19,10.1021/cen-09808-scicon8,,,,"hina continues to fight the outbreak of a novel coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has infected tens of thousands and killed more than 2,100 people since the end of 2019. The outbreak’s hot spot is in the central province of Hubei, in particular, its capital city Wuhan, where there have been more than 62,000 infections and 2,029 deaths as of last week, according to the World Health Organization (WHO). There, doctors and scientists are desperately struggling to find reliable ways to diagnose infected patients to help treat them and control the spread of the virus. The struggle has involved two diagnostic options—computed tomography (CT) scans of patients’ lungs and a nucleic acid lab test—each with advantages and disadvantages. With “a suddenly rampant new virus, it is normal to have multiple test approaches,” says a virologist at the Chinese Center for Disease Control and Prevention",2020,,C&EN Global Enterprise,2095772697,#1882,
,CZI,"Coronavirus latest: children are as susceptible as adults, study suggests",10.1037/11533-000,,,,"Updates on the respiratory illness that has infected tens of thousands of people and killed thousands. Children are just as likely to get infected with the new coronavirus as adults, finds one of the most detailed studies yet published on the spread of the virus, known as SARS-CoV-2. The analysis — based on data from Shenzhen, China — provides a partial answer to one of the most pressing questions surrounding the outbreak: the role of children.",2020,Nature,Nature,653912363,#4490,
,CZI,Coronavirus latest: Scientists clash over virus name,10.1038/531426a,,,,"Some researchers in China are unhappy with the designated name for the new coronavirus, SARS-CoV-2. They worry that the use of ‘SARS-CoV’ will confuse the public and impede efforts to control the pathogen’s spread.",2020,Nature,Nature,2307634664,#827,
,CZI,Therapeutic options for the 2019 novel coronavirus (2019-nCoV),10.1038/d41573-020-00016-0,,,,"Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV, some of which are already moving into clinical trials. Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV, some of which are already moving into clinical trials.",2020,"Li, Guangdi; Clercq, Erik De",Nature Reviews Drug Discovery,3004894342,#606,
,CZI,New virus in China requires international control effort,10.1038/d41586-020-00135-z,,,,,2020,"Liu, S. L.",Nature,3000446153,#303,
,CZI,Stop the Wuhan virus,10.1038/d41586-020-00153-x,,,,"Vigilance, preparedness, speed, transparency and global coordination are now crucial to stopping a new infectious disease from becoming a global emergency. [Figure not available: see fulltext.].",2020,,Nature,3000892382,#94,
,CZI,Coronavirus latest: WHO says outbreak is not yet pandemic,10.1038/d41586-020-00154-w,,,,"Scientists are concerned about a new virus that has infected tens of thousands of people and killed more than 2,000. The virus, which emerged in the Chinese city of Wuhan in December, is a coronavirus and belongs to the same family as the pathogen that causes severe acute respiratory syndrome, or SARS. It causes a respiratory illness called COVID-19, which can spread from person to person. Here’s the latest news on the outbreak. 24 February 16:30 GMT — WHO says outbreak isn’t a pandemic At a press briefing on 24 February, the World Health Organization (WHO) said that, despite the spread of the disease, the coronavirus outbreak does not yet amount to a pandemic. “Using the word pandemic now does not fit the facts, but it may cause fear,” said WHO director-general Tedros Adhanom Ghebreyesus.",2020,,Nature,3004083679,#1875,
,CZI,Coronavirus latest: Trump requests $2.5 billion for coronavirus response,10.1038/d41586-020-00154-w,,,,"Trump requests emergency funding for coronavirus response The White House on 24 February requested up to $2.5 billion to fund the US response to COVID-19. In a letter to Congress, the Office of Management and Budget requested $1.25 billion in new funding and proposed to make up the rest by repurposing funds allocated to other programs, including $535 million assigned to the Ebola response.Updates on the respiratory illness that has infected tens of thousands of people. Updates on the respiratory illness that has infected tens of thousands of people.",2020,,Nature,2143542499,#2033,
,CZI,"Coronavirus latest: global infections pass 90,000",10.1038/d41586-020-00154-w,,,,"Updates on the respiratory illness that has infected tens of thousands of people. The number of people worldwide who have been infected with the coronavirus has passed 90,000. More than 3,000 people have died since the outbreak began in December. The vast majority of cases — more than 80,000 — have occurred in China, but around 60 other countries are now also dealing with outbreaks. Many nations are preparing for a global pandemic, as reports of cases caused by community spread — rather than importation from China — rise. South Korea, Italy and Iran are fighting the largest outbreaks outside of China.",2020,Nature,Nature,2475094986,#3142,
,CZI,Coronavirus latest: First infection detected in Africa,10.1038/d41586-020-00154-w,,,,Updates on the respiratory illness that has infected tens of thousands of people. Updates on the respiratory illness that has infected tens of thousands of people.,2020,Nature,Nature,2170093155,#1037,
,CZI,Coronavirus latest: Chinese cases spike after changes to diagnosis method,10.1038/d41586-020-00154-w,,,,Updates on the respiratory illness that has infected tens of thousands of people. Updates on the respiratory illness that has infected tens of thousands of people.,2020,,Nature,3004780074,#888,
,CZI,Coronavirus latest: deaths in China surpass SARS toll,10.1038/d41586-020-00154-w,,,,"Updates on the respiratory illness that has infected tens of thousands of people. Updates on the respiratory illness that has infected tens of thousands of people. Here’s the latest news on the outbreak. 10 February 04:30 GMT — Deaths in China surpass toll from SARS More than 900 people in China have died from the new virus, a greater number than those who died from severe acute respiratory syndrome (SARS) in the 2002–03 epidemic. That outbreak, which also originated in China, killed 774 people worldwide. The number of people in the country infected with the new coronavirus has risen to 40,171, according to the latest update from China‘s National Health Commission.",2020,Nature,Nature,3004892222,#559,
,CZI,"Coronavirus latest: infections in China pass 20,000",10.1038/d41586-020-00154-w,,,,Updates on the respiratory illness that has infected thousands of people. Updates on the respiratory illness that has infected thousands of people.,2020,,Nature,3004912618,#290,
,CZI,China coronavirus: Six questions scientists are asking,10.1038/d41586-020-00166-6,,31992880,,,2020,"Callaway, E.; Cyranoski, D.",Nature,3001388158,#237,
,CZI,Coronavirus outbreak: what's next?,10.1038/d41586-020-00236-9,,32020111,,,2020,"Lewis, Dyani",Nature,3004083679,#311,
,CZI,China coronavirus: labs worldwide scramble to analyse live samples,10.1038/d41586-020-00262-7,,32020116,,,2020,"Callaway, Ewen",Nature,3004196996,#339,
,CZI,"Calling all coronavirus researchers: keep sharing, stay open",10.1038/d41586-020-00307-x,,32020126,,,2020,,Nature,2946951548,#350,
,CZI,Coronavirus: hospitals must learn from past pandemics,10.1038/d41586-020-00354-4,,,,"Use techniques honed during the SARS, H1N1 and Ebola epidemics to separate sick and well, keep workers safe and prepare for the next outbreak, says Nahid Bhadelia Use techniques honed during the SARS, H1N1 and Ebola epidemics to separate sick and well, keep workers safe and prepare for the next outbreak, says Nahid Bhadelia",2020,"Bhadelia, Nahid",Nature,3006492624,#794,
,CZI,When will the coronavirus outbreak peak?,10.1038/d41586-020-00361-5,,,,"Officials want to know but predictions vary wildly, from now to after hundreds of millions of people are infected. Officials want to know but predictions vary wildly, from now to after hundreds of millions of people are infected.",2020,"Cyranoski, David",Nature,3005762913,#1152,
,CZI,Did pangolins spread the China coronavirus to people?,10.1038/d41586-020-00364-2,,,,Genetic sequences of viruses isolated from the scaly animals are 99% similar to that of the circulating virus — but the work is yet to be formally published. Genetic sequences of viruses isolated from the scaly animals are 99% similar to that of the circulating virus — but the work is yet to be formally published.,2020,"Cyranoski, David",Nature,3004620471,#502,
,CZI,Coronavirus: why a permanent ban on wildlife trade might not work in China,10.1038/d41586-020-00377-x,,,,,2020,"Ribeiro, Joana; Bingre, Pedro; Strubbe, Diederik; Reino, Luís",Nature,3005823408,#738,
,CZI,China: clamp down on violations of wildlife trade ban,10.1038/d41586-020-00378-w,,,,,2020,"Zhou, Z. M.; Buesching, C. D.; Macdonald, D. W.; Newman, C.",Nature,3005823978,#2482,
,CZI,Why does the coronavirus spread so easily between people?,10.1038/d41586-020-00405-w,,,,"As the number of coronavirus infections approaches 100,000 people worldwide, researchers are racing to understand what makes it spread so easily. A handful of genetic and structural analyses have identified a key feature of the virus — a protein on its surface — that might explain why it infects human cells so readily. Other groups are investigating the doorway through which the new coronavirus enters human tissues — a receptor on cell membranes. Both the cell receptor and the virus protein offer potential targets for drugs to block the pathogen, but researchers say it is too early to be sure. “Understanding transmission of the virus is key to its containment and future prevention,” says David Veesler, a structural virologist at the University of Washington in Seattle, who posted his team’s findings about the virus protein on the biomedical preprint server bioRxiv on 20 February1. The new virus spreads much more readily than the one that caused severe acute respiratory syndrome, or SARS (also a coronavirus), and has infected more than ten times the number of people who contracted SARS.",2020,"Mallapaty, Smriti",,3005674816,#4897,
,CZI,Scientists fear coronavirus spread in countries least able to contain it,10.1038/d41586-020-00405-w,,,,Concerns are rising about the virus’s potential to circulate undetected in Africa and Asia. Concerns are rising about the virus’s potential to circulate undetected in Africa and Asia.,2020,"Mallapaty, Smriti",Nature,3005674816,#751,
,CZI,Daily briefing: The potential for repurposing existing drugs to fight COVID-19 coronavirus,10.1038/d41586-020-00412-x,,,,"Time is of the essence — here’s what we’ve already got. Plus, biology’s cryo-electron microscopy boom and why Scotland is bringing back bogs. Time is of the essence — here’s what we’ve already got. Plus, biology’s cryo-electron microscopy boom and why Scotland is bringing back bogs.",2020,"Graham, Flora",Nature,2793560999,#776,
,CZI,More than 80 clinical trials launch to test coronavirus treatments,10.1038/d41586-020-00444-3,,,,"As HIV drugs, stem cells and traditional Chinese medicines vie for a chance to prove their worth, the WHO attempts to bring order to the search. As HIV drugs, stem cells and traditional Chinese medicines vie for a chance to prove their worth, the WHO attempts to bring order to the search.",2020,Nature,Nature,3005925177,#886,
,CZI,Avoid stigmatizing names for 2019 novel coronavirus,10.1038/d41586-020-00458-x,,32071450,,,2020,"Shu, Lele",Nature,3005489812,#1271,
,CZI,‘No one is allowed to go out’: your stories from the coronavirus outbreak,10.1038/d41586-020-00478-7,,,,"From laboratory closures to equipment shortages, researchers worldwide tell Nature how they have been affected by the epidemic. ‘No one is allowed out’: readers tell Nature about their experiences. The outbreak of a new coronavirus is wreaking havoc worldwide. In China, the epicentre of the epidemic, the virus has infected tens of thousands of people and killed more than 2,100. Unprecedented measures meant to contain the spread have brought millions of daily lives to a halt, and the effects have touched economies and global supply chains.",2020,"Stoye, Emma",Nature,,#1764,
,CZI,Mystery deepens over animal source of coronavirus,10.1038/d41586-020-00548-w,,32127703,,,2020,"Cyranoski, David",Nature,1504098263,#4350,
,CZI,Mystery deepens over animal source of coronavirus Podcast Extra: ‘There is lots of anxiety’: a scientist’s view from South Korea Coronavirus latest: Brazil reports first case in South America,10.1038/d41586-020-00548-w 10.1038/d41586-020-00565-9 10.1038/d41586-020-00154-w,,,,"Pangolins are a prime suspect, but a slew of genetic analyses has yet to find conclusive proof. Pangolins are a prime suspect, but a slew of genetic analyses has yet to find conclusive proof. Nick Howe speaks to chemist Bartosz Grzybowski about his experience with the coronavirus outbreak in South Korea. Nick Howe speaks to chemist Bartosz Grzybowski about his experience with the coronavirus outbreak in South Korea. A case of COVID-19 has been confirmed in Brazil — the first in South America. On 26 February, Brazil’s minister of health, Luiz Henrique Mandetta, confirmed that a man who traveled to northern Italy between 9 and 21 February has the disease. Italy’s outbreak has escalated to 324 cases and 12 deaths, according to a virus tracker maintained by Johns Hopkins University in Baltimore, Maryland.",2020,"Cyranoski, David; Grzybowski, Bartosz; Nature",Nature,,#2315,
,CZI,Time to use the p-word? Coronavirus enters dangerous new phase,10.1038/d41586-020-00551-1,,,,"As outbreaks surge worldwide, scientists fear that COVID-19 might soon become pandemic. As outbreaks surge worldwide, scientists fear that COVID-19 might soon become pandemic.",2020,"Callaway, Ewen",Nature,2031123810,#2009,
,CZI,Daily briefing: When a tiny lab accident almost leads to amputation,10.1038/d41586-020-00581-9,,,,"Three weeks ago, on the basis of genetic analyses, pangolins became the prime suspect as the animal source of the coronavirus that causes COVID-19. Further analysis of those data — alongside three other genome studies of pangolin coronaviruses — shows that although the scaly anteater is still a contender, the link is far from conclusive. Whatever the source, scientists emphasize that animals should not be vilified for their role in the outbreak. “The problem is not the animals, it’s that we get in contact with them,” says animal-behaviour researcher Sara Platto. (Nature | 4 min read)",2020,"Graham, Flora",Nature,2416623887,#2638,
,CZI,"Coronavirus nixes conference, twilight zone beckons and a faded star brightens",10.1038/d41586-020-00589-1,,,,"Coronavirus enters dangerous new phase The new coronavirus has spread to more than 70 nations and the total number of infections worldwide had passed 90,000 as Nature went to press (see ‘Rapid spread’). Researchers have warned that the surge in outbreaks outside China, where the virus emerged and most cases have occurred, means that the coronavirus is becoming unstoppable. The World Health Organization has resisted describing the situation as a pandemic. Director-general Tedros Adhanom Ghebreyesus said on 2 March that there was still a chance of containing the virus. Mike Ryan, director of the WHO’s emergencies programme, said that using the word pandemic would mean that efforts to contain and slow the spread of the virus have failed, which has proved untrue in China, Singapore and other regions. But other scientists say the surge in international cases marks a tipping point. “I think the epidemiological conditions for a pandemic are met,” says Marc Lipsitch, an infectious-disease epidemiologist at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts. He and others say that although containment measures seem to have kept outbreaks from escalating outside China for more than a month, such procedures might soon become unfeasible on a broader scale. Those efforts have involved quickly identifying infected people and their close contacts, and isolating them to prevent further transmission. “We’ve got to think more carefully about what measures might be sustainable in terms of reducing transmission without shutting down cities completely and stopping people from moving,” says Ben Cowling, an infectious-disease epidemiologist at the University of Hong Kong. The efforts include ‘social distancing’, which reduces the average chances that uninfected people will encounter an infected person. But some epidemiologists say too little is known about the outbreak to deploy this effectively.",2020,Nature,Nature,2281645967,#4920,
,CZI,Behind the scenes in the biosafety office,10.1038/d41586-020-00593-5,,,,It’s never a dull day for those tasked with keeping biological research safe for all.,2020,"Powell, Kendall",Nature,2041620149,#3902,
,CZI,Backchat: Covering coronavirus,10.1038/d41586-020-00598-0,,,,"In this edition of Backchat we take a deep dive into Nature's coverage of coronavirus. As cases climb, what are some of the challenges involved in reporting on the virus? Nick Howe hosts our roundtable discussion, with guests Ewen Callaway, Nisha Gaind, and David Cyranoski. Nick Howe hosts our roundtable discussion, with guests Ewen Callaway, Nisha Gaind, and David Cyranoski.",2020,,Nature,3004280078,#2995,
,CZI,Open peer-review platform for COVID-19 preprints,10.1038/d41586-020-00613-4,,32127711,,,2020,"Johansson, Michael A.; Saderi, Daniela",Nature,2301495257,#4351,
,CZI,Coronavirus response: a focus on containment is still apt,10.1038/d41586-020-00623-2,,32127714,,,2020,,Nature,3005352349,#4349,
,CZI,Coronavirus and the race to distribute reliable diagnostics,10.1038/d41587-020-00002-2,,,,International teams worked at speed to make tests for the virus available in record time. The medical community is rallying to develop a set of rapid and reliable molecular diagnostic tests for the new human coronavirus that appeared in China — now dubbed sudden acute respiratory syndrome coronavirus-2 (SARS-CoV-2).,2020,Nature,Nature,2094269437,#1369,
,CZI,Coronavirus puts drug repurposing on the fast track,10.1038/d41587-020-00003-1,,,,Existing antivirals and knowledge gained from the SARS and MERS outbreaks gain traction as the fastest route to fight the current coronavirus epidemic. Existing antivirals and knowledge gained from the SARS and MERS outbreaks gain traction as the fastest route to fight the current coronavirus epidemic.,2020,"Harrison, Charlotte",Nature Biotechnology,2910217498,#2629,
,CZI,Four ways researchers are responding to the COVID-19 outbreak,10.1038/d41591-020-00002-4,,,,How did researchers react so quickly to the SARS-CoV-2 epidemic? Nature Medicine has asked some key experts. How did researchers react so quickly to the SARS-CoV-2 epidemic? Nature Medicine has asked some key experts.,2020,"Keener, Amanda B.",Nature Medicine,3006304371,#1368,
,CZI,Functional Cell Receptors for Human Coronavirus,10.1038/nature12328,,,,"Viruses infect host cells by binding to receptors on thesurface of cells. Receptor is an important factor affecting host range and interspecific transmission. In December 2019, an outbreak of unexplained pneumonia occurred in Wuhan, Hubei province. The pathogen was a new coronavirus, named 2019 NovelCoronavirus (2019-nCoV) by WHO. Angiotensin-converting enzyme 2 (ACE2) was found to be the receptor of 2019-nCoV.This review provides a brief overview of human coronavirus receptors and their applications, with a view to providing references for the tracing, cross-species transmission, epidemiological analysis and antiviral and vaccine studies of 2019-nCoV.",2020,"YAN, Li; XIANG, Jie; CUI, Tianpen",Chinese Journal of Laboratory Medicine,2120967846,#2095,
,CZI,Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor,10.1038/nature12711,,24172901,,"The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history. An ongoing outbreak of Middle East respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.",2013,"Ge, Xing-Yi; Li, Jia-Lu; Yang, Xing-Lou; Chmura, Aleksei A.; Zhu, Guangjian; Epstein, Jonathan H.; Mazet, Jonna K.; Hu, Ben; Zhang, Wei; Peng, Cheng; Zhang, Yu-Ji; Luo, Chu-Ming; Tan, Bing; Wang, Ning; Zhu, Yan; Crameri, Gary; Zhang, Shu-Yi; Wang, Lin-Fa; Daszak, Peter; Shi, Zheng-Li",Nature,1993577573,#1398,
,CZI,A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence,10.1038/nm.3985,,26552008,,"The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.",2015,"Menachery, Vineet D.; Yount, Boyd L., Jr.; Debbink, Kari; Agnihothram, Sudhakar; Gralinski, Lisa E.; Plante, Jessica A.; Graham, Rachel L.; Scobey, Trevor; Ge, Xing-Yi; Donaldson, Eric F.; Randell, Scott H.; Lanzavecchia, Antonio; Marasco, Wayne A.; Shi, Zhengli-Li; Baric, Ralph S.",Nat Med,2195009776,#1374,
,CZI,SARS and MERS: recent insights into emerging coronaviruses,10.1038/nrmicro.2016.81,,27344959,,"The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses.",2016,"de Wit, Emmie; van Doremalen, Neeltje; Falzarano, Darryl; Munster, Vincent J.",Nat Rev Microbiol,2470646526,#1404,
,CZI,NOVEL CORONAVIRUS THAT RECENTLY EMERGED IN CHINA,10.1038/s41422-020-0282-0,,32048481,,,2020,"Israeli, Eitan",Harefuah,3005212621,#767,
,CZI,Virus against virus: a potential treatment for 2019-nCov (SARS-CoV-2) and other RNA viruses,10.1038/s41422-020-0290-0,,32071427,,,2020,"Nguyen, Tuan M.; Zhang, Yang; Pandolfi, Pier Paolo",Cell Res,3004310457,#1280,
,CZI,A novel coronavirus (2019-nCoV) causing pneumonia-associated respiratory syndrome,10.1038/s41423-020-0372-4,,,,,2020,"Jiang, Shibo; Xia, Shuai; Ying, Tianlei; Lu, Lu",Cellular & Molecular Immunology AB -The novel coronavirus was denoted as 2019-nCoV by WHO (https://www.who.int/emergencies/diseases/novel-coronavirus-2019) and the Wuhan pneumonia was named as novel coronavirus-infected pneumonia (NCIP) by Chinese scient,3005255913,#243,
,CZI,Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein,10.1038/s41423-020-0374-2,,,,,2020,"Xia, Shuai; Zhu, Yun; Liu, Meiqin; Lan, Qiaoshuai; Xu, Wei; Wu, Yanling; Ying, Tianlei; Liu, Shuwen; Shi, Zhengli; Jiang, Shibo; Lu, Lu",Cellular & Molecular Immunology,3006116465,#581,
,CZI,Epitopes for a 2019-nCoV vaccine,10.1038/s41423-020-0377-z,,,,,2020,"Lucchese, Guglielmo",Cellular & Molecular Immunology,3006116465,#1806,
,CZI,Novel antibody epitopes dominate the antigenicity of spike glycoprotein in SARS-CoV-2 compared to SARS-CoV,10.1038/s41423-020-0385-z,,,,,2020,"Zheng, Ming; Song, Lun",Cellular & Molecular Immunology,2092639010,#4320,
,CZI,Prevent and predict,10.1038/s41559-020-1150-5,,,,"As the COVID-19 outbreak continues, the next pandemic could be prevented by ending the wildlife trade and reinvesting in the monitoring of potential zoonoses.",2020,Nature,Nature Ecology & Evolution,1973735196,#1370,
,CZI,Rapid outbreak response requires trust,10.1038/s41564-020-0670-8,,,,,2020,,Nature Microbiology,2990816838,#644,
,CZI,Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses,10.1038/s41564-020-0688-y,,32094589,,"Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS-CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here, we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent SARS-CoV-2, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells, and confirm that human ACE2 is the receptor for the recently emerging SARS-CoV-2.",2020,"Letko, Michael; Marzi, Andrea; Munster, Vincent",Nat Microbiol,3006448444,#1966,
,CZI,We shouldn't worry when a virus mutates during disease outbreaks,10.1038/s41564-020-0690-4,,,,"Mutation. The word naturally conjures fears of unexpected and freakish changes. Ill-informed discussions of mutations thrive during virus outbreaks, including the ongoing spread of SARS-CoV-2. In reality, mutations are a natural part of the virus life cycle and rarely impact outbreaks dramatically.",2020,"Grubaugh, Nathan D.; Petrone, Mary E.; Holmes, Edward C.",Nature Microbiology,2030160453,#4129,
,CZI,COVID-19 and the cardiovascular system,10.1038/s41569-020-0360-5,,,,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system. Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.",2020,"Zheng, Ying-Ying; Ma, Yi-Tong; Zhang, Jin-Ying; Xie, Xiang",Nature Reviews Cardiology,2105828115,#5518,
,CZI,Outbreak of a novel coronavirus,10.1038/s41579-020-0332-0,,,,,2020,"Du Toit, A.",Nature reviews. Microbiology,3004886529,#103,
,CZI,Novel coronavirus takes flight from bats?,10.1038/s41579-020-0336-9,,,,Two recent studies provide initial insights into a novel coronavirus that is associated with an outbreak of human respiratory disease.,2020,"York, Ashley",Nature Reviews Microbiology,3006139879,#713,
,CZI,Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin,10.1038/s41586-018-0010-9,,29618817,,"Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health (1) . Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS) (2-10) . Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.",2018,"Zhou, Peng; Fan, Hang; Lan, Tian; Yang, Xing-Lou; Shi, Wei-Feng; Zhang, Wei; Zhu, Yan; Zhang, Ya-Wei; Xie, Qing-Mei; Mani, Shailendra; Zheng, Xiao-Shuang; Li, Bei; Li, Jin-Man; Guo, Hua; Pei, Guang-Qian; An, Xiao-Ping; Chen, Jun-Wei; Zhou, Ling; Mai, Kai-Jie; Wu, Zi-Xian; Li, Di; Anderson, Danielle E.; Zhang, Li-Biao; Li, Shi-Yue; Mi, Zhi-Qiang; He, Tong-Tong; Cong, Feng; Guo, Peng-Ju; Huang, Ren; Luo, Yun; Liu, Xiang-Ling; Chen, Jing; Huang, Yong; Sun, Qiang; Zhang, Xiang-Li-Lan; Wang, Yuan-Yuan; Xing, Shao-Zhen; Chen, Yan-Shan; Sun, Yuan; Li, Juan; Daszak, Peter; Wang, Lin-Fa; Shi, Zheng-Li; Tong, Yi-Gang; Ma, Jing-Yun",Nature,2794573360,#1342,
,CZI,China’s response to a novel coronavirus stands in stark contrast to the 2002 SARS outbreak response,10.1038/s41591-020-0771-1,,,,,2020,"Nkengasong, J.",Nature Medicine,,#150,
,CZI,"Communication, collaboration and cooperation can stop the 2019 coronavirus",10.1038/s41591-020-0775-x,,32015560,,,2020,,Nat Med,2095522790,#349,
,CZI,Emergence of a novel human coronavirus threatening human health,10.1038/s41591-020-0796-5,,,,"In late December 2019, a cluster of patients with ‘atypical pneumonia’ of unknown etiology was reported in Wuhan, China. A novel human coronavirus, now provisionally called ‘SARS-CoV-2’, was identified as the cause of this disease, now named ‘COVID-19’.",2020,"Poon, Leo L. M.; Peiris, Malik",Nature Medicine,2127593754,#2567,
,CZI,Author Correction: China's response to a novel coronavirus stands in stark contrast to the 2002 SARS outbreak response,10.1038/s41591-020-0816-5,,32139890,,An amendment to this paper has been published and can be accessed via a link at the top of the paper.,2020,"Nkengasong, J.",Nature medicine,3002119243,#4926,
,CZI,Early clinical manifestations and pulmonary imaging analysis of patients with Novel coronavirus pneumonia,10.1038/s41598-019-40799-w,,,,"Objective To investigate the early clinical characteristics and radiographic changes in confirmed Novel coronavirus pneumonia (NCP) and excluded NCP patients. Methods Twenty-four patients with suspected NCP admitted to Shanghai Jiao Tong University Affiliated Sixth People’s Hospital and Jinshan Branch Hospital between January and February, 2020 were chosen as our research subjects. Early clinical features and radiographic changes were analyzed in 10 patients of confirmed NCP and 14 patients of excluded NCP. Results In the early stage, all 24 suspected patients were mild, and had normal blood gas analysis. Of 10 diagnosed patients, 50% were male. All the 10 patients had fever and fatigue, with body temperature between 37.5℃ and 38.5℃. Only 1 patient had dry cough. 2 patients had no clear epidemiological exposure history, the other 8 had a clear epidemiological exposure, with a possible incubation period of 1-10 days. From CT imaging, lesions were characterized as ground glass shadow ( n =9), which could be unilateral ( n =1) or bilateral ( n =9), and were mainly close to the pleura ( n =9), with nodule shadow ( n =1) and without focal necrosis, and could combined with pleural effusion ( n =1. Among patients excluded NCP, all 14 patients had a clear history of epidemic exposure, with an onset time of 1 to 13 days. 12 patients had fever , including 4 with temperature > 38.5°C, 8 with temperature 37.3-38.5°C, and 2 without fever. All patients had fatigue , 7 patients had dry cough and 2 patients had chest pain. From CT imaging, ground glass shadow appeared in 4 patients , lesions were unilateral in 10 patients and bilateral in 4 patients , and the lesions were relatively sporadic, without necrosis or pleural effusion. Conclusion 1.Not all patients with NCP have a direct history of epidemiology exposure, some patients may be infected unknowingly. 2. According to CT imaging, NCP seems to have no special manifestations different from other viral pneumonia. 3. NCP is more common among middle-aged people.",2020,"YANG, Tao; YU, Xiaona; HE, Xingxing; ZHOU, Wei; FU, Yifu; FENG, QiMing",Chinese Journal of Emergency Medicine,2921678383,#2090,
,CZI,Strategy of hospital logistic support to the battle against novel coronavirus pneumonia,10.1039/C6CS00898D,,,,"Nowadays hospitals have been at the forefront fighting against novel coronavirus pneumonia, with diagnosing and treating of patients as a top priority. In order to ensure the smooth progress of diagnosis and treatment, and prevent the occurrence of nosocomial infection, logistics support needs to make allowances for the isolation ward in time from the perspectives of logistics, facilities and equipment, and to transform the in-and-out double channels of ward access as required, thus setting up the partition of the three zones. Secondly, logistics support needs to optimize the logistics service workflow, including the medical waste management, the environmental disinfection isolation, and to optimize the catering service within hospitals to reduce the gathering and flow of personnel. Thirdly, logistics support needs to increase personnel training, and to eliminate psychological panic as well as to stabilize the logistics support team by putting logistics management cadres on the front line. Meanwhile, the logistics department needs to take over the hospital access screening work, strictly manage those who enter the hospital, maximize the safety and reliability of the logistics support within the hospital, and ensure the smooth progress of the epidemic prevention work.",2020,"CHEN, Changgui; XUAN, Junfang; HUANG, Xiaohua; SHOU, Hongyan; FU, Jinhong; WANG, Gongyi; CAI, Zhaobin",Chinese Journal of Hospital Administration,2762136999,#2342,
,CZI,Processing of the SARS-CoV pp1a/ab nsp7-10 region,10.1042/BCJ20200029,,32083638,,"Severe acute respiratory syndrome coronavirus (SARS-CoV) is the causative agent of a respiratory disease with a high case fatality rate. During the formation of the coronaviral replication/transcription complex (RTC), essential steps include processing of the conserved polyprotein nsp7-10 region by the main protease Mpro and subsequent complex formation of the released nsp's. Here, we analyzed processing of the coronavirus nsp7-10 region using native mass spectrometry showing consumption of substrate, rise and fall of intermediate products and complexation. Importantly, there is a clear order of cleavage efficiencies, which is influenced by the polyprotein tertiary structure. Furthermore, the predominant product is an nsp7+8(2:2) hetero-tetramer with nsp8 scaffold. In conclusion, native MS, opposed to other methods, can expose the processing dynamics of viral polyproteins and the landscape of protein interactions in one set of experiments. Thereby, new insights into protein interactions, essential for generation of viral progeny, were provided, with relevance for development of antivirals.",2020,"Krichel, Boris; Falke, Sven; Hilgenfeld, Rolf; Redecke, Lars; Uetrecht, Charlotte",Biochem J,2990067939,#1601,
,CZI,COVID-19: Gastrointestinal manifestations and potential fecal-oral transmission,10.1053/j.gastro.2020.02.054,,,,,2020,"Gu, Jinyang; Han, Bing; Wang, Jian",Gastroenterology,2793345173,#4567,
,CZI,Evidence for gastrointestinal infection of SARS-CoV-2,10.1053/j.gastro.2020.02.055,,,,,2020,"Xiao, Fei; Tang, Meiwen; Zheng, Xiaobin; Liu, Ye; Li, Xiaofeng; Shan, Hong",Gastroenterology,3005688502,#4401,
,CZI,Anesthetic Management of Patients with Suspected 2019 Novel Coronavirus Infection During Emergency Procedures,10.1053/j.jvca.2020.02.039,,,,"Objectives To prevent cross-infection in the operating rooms by taking anesthesia management procedures for emergency procedures in patients with confirmed or suspected 2019-nCoV, and report clinical and anesthesia-related characteristics of these patients. Design This was a retrospective, multicenter clinical study. Setting This study used a multicenter dataset from four hospitals in Wuhan, China. Participants Patients and healthcare providers with confirmed or suspected 2019-nCoV from Jan 23 to Jan 31, 2020, at Wuhan Union Hospital, Wuhan Children's Hospital, The Central Hospital of Wuhan and Wuhan Fourth Hospital in Wuhan, China. Interventions Anesthetic management and infection control guidelines for emergency procedures in patients with suspected 2019-nCoV were drafted and applied in four hospitals in Wuhan. Measurements and Main Results Cross-infection in the operating rooms of these four hospitals has been effectively reduced by taking these measures and procedures. As for patients with laboratory-confirmed 2019-nCoV infection or suspected infection, majority of them were female (23 [62%] of 37); with a mean age of 41.0 years old (SD, 19.6; range, 4 to 78). Ten (27%) patients had chronic medical illness, including 4 (11%) with diabetes, 8 (22%) with hypertension, and 8 (22%) with digestive system disease. Twenty-five (68%) patients showed lymphopenia and 23 (62%) patients exhibited multiple mottling and ground-glass opacity on CT scanning. Conclusions Our study indicated that 2019-nCoV specific guidelines for emergency procedures in patients with confirmed or suspected 2019-nCoV may effectively prevent cross-infection in the operating rooms. Most patients with confirmed or suspected 2019-nCoV presented with fever, dry cough, and developed bilateral multiple mottling and ground-glass opacity on chest CT scans.",2020,"Zhao, Shuai; Ling, Ken; Yan, Hong; Zhong, Liang; Peng, Xiaohong; Yao, Shanglong; Huang, Jiapeng; Chen, Xiangdong",Journal of Cardiothoracic and Vascular Anesthesia,2883079614,#2485,
,CZI,Importation and Human-to-Human Transmission of a Novel Coronavirus in Vietnam,10.1056/NEJMc2001272,,,,,2020,"Phan, Lan T.; Nguyen, Thuong V.; Luong, Quang C.; Nguyen, Thinh V.; Nguyen, Hieu T.; Le, Hung Q.; Nguyen, Thuc T.; Cao, Thang M.; Pham, Quang D.",New England Journal of Medicine,3003951199,#50,
,CZI,Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany,10.1056/NEJMc2001468,,32003551,,,2020,"Rothe, C.; Schunk, M.; Sothmann, P.; Bretzel, G.; Froeschl, G.; Wallrauch, C.; Zimmer, T.; Thiel, V.; Janke, C.; Guggemos, W.; Seilmaier, M.; Drosten, C.; Vollmar, P.; Zwirglmaier, K.; Zange, S.; Wolfel, R.; Hoelscher, M.",The New England journal of medicine,3004239190,#92,
,CZI,A Locally Transmitted Case of SARS-CoV-2 Infection in Taiwan,10.1056/NEJMc2001573,,,,"On January 25, 2020, a 52-year-old woman with a history of type 2 diabetes presented with fever to an emergency department in central Taiwan. She was admitted to the hospital because of suspicion of pneumonia associated with SARS-CoV-2 infection. She had lived in Wuhan from October 21, 2019, to January 20, 2020. She returned to Taiwan from Wuhan on January 20 on an airplane. On the same day, a throat swab was obtained from another passenger on that flight; that passenger was confirmed to have the first known imported case of SARS-CoV-2 infection in Taiwan when the swab was found to be positive for the virus on January 21.",2020,"Liu, Ying-Chu; Liao, Ching-Hui; Chang, Chin-Fu; Chou, Chu-Chung; Lin, Yan-Ren",New England Journal of Medicine,3005688502,#755,
,CZI,Journey of a Thai Taxi Driver and Novel Coronavirus,10.1056/NEJMc2001621,,,,"On January 20, 2020, a 51-year-old male taxi driver had fever, cough, and myalgia and went to a local pharmacy to get unspecified over-the-counter medications. At the time, he was not aware of the emergence of SARS-CoV-2 or the illness it causes (Covid-19). As the symptoms persisted, he decided to visit a private primary care clinic in Bangkok on January 23. The body temperature was 36.8°C (98°F). The clinic physician ordered a throat swab for influenza A and B; the swab was negative for both strains. Additional medications were prescribed for treatment of the patient’s symptoms.",2020,"Pongpirul, Wannarat A.; Pongpirul, Krit; Ratnarathon, Anuttra C.; Prasithsirikul, Wisit",New England Journal of Medicine,3006119592,#743,
,CZI,SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients,10.1056/NEJMc2001737,,,,,2020,"Zou, Lirong; Ruan, Feng; Huang, Mingxing; Liang, Lijun; Huang, Huitao; Hong, Zhongsi; Yu, Jianxiang; Kang, Min; Song, Yingchao; Xia, Jinyu; Guo, Qianfang; Song, Tie; He, Jianfeng; Yen, Hui-Ling; Peiris, Malik; Wu, Jie",New England Journal of Medicine,1942354472,#1253,
,CZI,"Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China",10.1056/NEJMc2001899,,,,,2020,"Hoehl, Sebastian; Berger, Annemarie; Kortenbusch, Marhild; Cinatl, Jindrich; Bojkova, Denisa; Rabenau, Holger; Behrens, Pia; Böddinghaus, Boris; Götsch, Udo; Naujoks, Frank; Neumann, Peter; Schork, Joscha; Tiarks-Jungk, Petra; Walczok, Antoni; Eickmann, Markus; Vehreschild, Maria J. G. T.; Kann, Gerrit; Wolf, Timo; Gottschalk, René; Ciesek, Sandra",New England Journal of Medicine,3006355661,#1184,
,CZI,"Another Decade, Another Coronavirus",10.1056/NEJMe2001126,,,,,2020,"Perlman, S.",The New England journal of medicine,3002715510,#154,
,CZI,Covid-19 — Navigating the Uncharted,10.1056/NEJMe2002387,,,,"In their Journal article, Li and colleagues3 provide a detailed clinical and epidemiologic description of the first 425 cases reported in the epicenter of the outbreak: the city of Wuhan in Hubei province, China. Although this information is critical in informing the appropriate response to this outbreak, as the authors point out, the study faces the limitation associated with reporting in real time the evolution of an emerging pathogen in its earliest stages. Nonetheless, a degree of clarity is emerging from this report. The median age of the patients was 59 years, with higher morbidity and mortality among the elderly and among those with coexisting conditions (similar to the situation with influenza); 56% of the patients were male. Of note, there were no cases in children younger than 15 years of age. Either children are less likely to become infected, which would have important epidemiologic implications, or their symptoms were so mild that their infection escaped detection, which has implications for the size of the denominator of total community infections.",2020,"Fauci, Anthony S.; Lane, H. Clifford; Redfield, Robert R.",New England Journal of Medicine,,#2804,
,CZI,Audio Interview: Preparing for the Spread of Covid-19,10.1056/NEJMe2003319,,32101683,,,2020,"Rubin, Eric J.; Baden, Lindsey R.; Morrissey, Stephen",N Engl J Med,3006612756,#2414,
,CZI,Audio Interview: What Clinicians Need to Know in Diagnosing and Treating Covid-19,10.1056/NEJMe2004244,,32130833,,,2020,"Rubin, Eric J.; Baden, Lindsey R.; Morrissey, Stephen",N Engl J Med,2921737714,#4456,
,CZI,Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia,10.1056/NEJMoa1211721,,23075143,,"A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.",2012,"Zaki, Ali M.; van Boheemen, Sander; Bestebroer, Theo M.; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.",N Engl J Med,2166867592,#1347,
,CZI,"A Novel Coronavirus from Patients with Pneumonia in China, 2019",10.1056/NEJMoa2001017,,31978945,,"In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed another clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).",2020,"Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao, X.; Huang, B.; Shi, W.; Lu, R.; Niu, P.; Zhan, F.; Ma, X.; Wang, D.; Xu, W.; Wu, G.; Gao, G. F.; Tan, W.",The New England journal of medicine,3001897055,#8,
,CZI,Current status and progress of 2019 novel coronavirus pneumonia,10.1056/NEJMoa2001017,,,,"Recently, the 2019 novel coronavirus (2019-nCoV) pneumonia outbroke in Wuhan and rapidly spread to all over China and even the world. Because of the strong infectivity and various clinical symptoms, it has brought certain difficulties to the epidemic prevention and control. Currently there is no specific drug for 2019-nCoV. Previous drugs used to treat other coronaviruses may be effective, but further clinical trials remain needed. We reviewed literature on the epidemiology, etiology, clinical manifestations, imaging manifestations, laboratory examination, diagnosis, complications, treatment and outcome of 2019-nCoV pneumonia.",2020,"YANG, Xinying; MIAO, Congliang; JIN, Mengdi; ZHOU, Dandan; ZHUANG, Jinqiang; HONG, Jiang",Chinese Critical Care Medicine,3001897055,#2088,
,CZI,Report of the first cases of mother and infant infections with 2019 novel coronavirus in Xinyang City Henan Province,10.1056/NEJMoa2001191,,,,"Objective To report the first case of a neonatal pneumonia with 2019-nCoV infection, and the experience of successfully diagnosis and treatment in late pregnancy woman with novel coronavirus pneumonia (critical type) in Xinyang city. Methods The successfully diagnosis and treatment of a woman with 38 weeks singleton pregnancy complicated with novel coronavirus pneumonia (critical type), and a case of neonatal pneumonia with 2019-nCoV infection were retrospectively analyzed. Results A single male was successfully delivered at 38-week gestation of his mother by cesarean section under third level protection in operation room. The delivery woman was diagnosed with 2019-nCoV infection at day 2 of delivery. Dyspnea and severe hypoxemia soon developed, and invasive mechanical ventilation was given. After active rescue and treatment, the delivery woman had been taken off line successfully and the condition was stable. Pharyngeal swab specimen of the neonate was sent for examination 3 days after birth, and was positive for novel coronavirus nucleic acid by fluorescence reverse transcript polymerase chain reaction. Conclusion 2019-nCoV may be transmitted vertically from mother to child.",2020,"LI, Mengdie; XU, Ming; ZHAN, Weiqiang; HAN, Tao; ZHANG, Guosheng; LU, Yibin",Chinese Journal of Infectious Diseases,3003465021,#2207,
,CZI,First Case of 2019 Novel Coronavirus in the United States,10.1056/NEJMoa2001191,,,,"On January 19, 2020, a 35-year-old man presented to an urgent care clinic in Snohomish County, Washington, with a 4-day history of cough and subjective fever. On checking into the clinic, the patient put on a mask in the waiting room. After waiting approximately 20 minutes, he was taken into an examination room and underwent evaluation by a provider. He disclosed that he had returned to Washington State on January 15 after traveling to visit family in Wuhan, China. The patient stated that he had seen a health alert from the U.S. Centers for Disease Control and Prevention (CDC) about the novel coronavirus outbreak in China and, because of his symptoms and recent travel, decided to see a health care provider.",2020,"Holshue, Michelle L.; DeBolt, Chas; Lindquist, Scott; Lofy, Kathy H.; Wiesman, John; Bruce, Hollianne; Spitters, Christopher; Ericson, Keith; Wilkerson, Sara; Tural, Ahmet; Diaz, George; Cohn, Amanda; Fox, LeAnne; Patel, Anita; Gerber, Susan I.; Kim, Lindsay; Tong, Suxiang; Lu, Xiaoyan; Lindstrom, Steve; Pallansch, Mark A.; Weldon, William C.; Biggs, Holly M.; Uyeki, Timothy M.; Pillai, Satish K.",New England Journal of Medicine,3003465021,#127,
,CZI,"Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia",10.1056/NEJMoa2001316,,,,,2020,"Li, Qun; Guan, Xuhua; Wu, Peng; Wang, Xiaoye; Zhou, Lei; Tong, Yeqing; Ren, Ruiqi; Leung, Kathy S. M.; Lau, Eric H. Y.; Wong, Jessica Y.; Xing, Xuesen; Xiang, Nijuan; Wu, Yang; Li, Chao; Chen, Qi; Li, Dan; Liu, Tian; Zhao, Jing; Li, Man; Tu, Wenxiao; Chen, Chuding; Jin, Lianmei; Yang, Rui; Wang, Qi; Zhou, Suhua; Wang, Rui; Liu, Hui; Luo, Yingbo; Liu, Yuan; Shao, Ge; Li, Huan; Tao, Zhongfa; Yang, Yang; Deng, Zhiqiang; Liu, Boxi; Ma, Zhitao; Zhang, Yanping; Shi, Guoqing; Lam, Tommy T. Y.; Wu, Joseph T. K.; Gao, George F.; Cowling, Benjamin J.; Yang, Bo; Leung, Gabriel M.; Feng, Zijian",New England Journal of Medicine,,#57,
,CZI,Clinical Characteristics of Coronavirus Disease 2019 in China,10.1056/NEJMoa2002032,,,,"BACKGROUND Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)",2020,"Guan, Wei-jie; Ni, Zheng-yi; Hu, Yu; Liang, Wen-hua; Ou, Chun-quan; He, Jian-xing; Liu, Lei; Shan, Hong; Lei, Chun-liang; Hui, David S. C.; Du, Bin; Li, Lan-juan; Zeng, Guang; Yuen, Kwok-Yung; Chen, Ru-chong; Tang, Chun-li; Wang, Tao; Chen, Ping-yan; Xiang, Jie; Li, Shi-yue; Wang, Jin-lin; Liang, Zi-jing; Peng, Yi-xiang; Wei, Li; Liu, Yong; Hu, Ya-hua; Peng, Peng; Wang, Jian-ming; Liu, Ji-yang; Chen, Zhong; Li, Gang; Zheng, Zhi-jian; Qiu, Shao-qin; Luo, Jie; Ye, Chang-jiang; Zhu, Shao-yong; Zhong, Nan-shan",New England Journal of Medicine,3005477624,#2822,
,CZI,A Novel Coronavirus Emerging in China - Key Questions for Impact Assessment,10.1056/NEJMp2000929,,31978293,,,2020,"Munster, V. J.; Koopmans, M.; van Doremalen, N.; van Riel, D.; de Wit, E.",The New England journal of medicine,3002533507,#9,
,CZI,Escaping Pandora's Box - Another Novel Coronavirus,10.1056/NEJMp2002106,,32101660,,,2020,"Morens, David M.; Daszak, Peter; Taubenberger, Jeffery K.",N Engl J Med,2260741209,#2163,
,CZI,Defining the Epidemiology of Covid-19 — Studies Needed,10.1056/NEJMp2002125,,,,,2020,"Lipsitch, Marc; Swerdlow, David L.; Finelli, Lyn",New England Journal of Medicine,,#1287,
,CZI,Responding to Covid-19 — A Once-in-a-Century Pandemic?,10.1056/NEJMp2003762,,,,"In any crisis, leaders have two equally important responsibilities: solve the immediate problem and keep it from happening again. The Covid-19 pandemic is a case in point. We need to save lives now while also improving the way we respond to outbreaks in general. The first point is more pressing, but the second has crucial long-term consequences. The long-term challenge — improving our ability to respond to outbreaks — isn’t new. Global health experts have been saying for years that another pandemic whose speed and severity rivaled those of the 1918 influenza epidemic was a matter not of if but of when.1 The Bill and Melinda Gates Foundation has committed substantial resources in recent years to helping the world prepare for such a scenario. Now we also face an immediate crisis. In the past week, Covid-19 has started behaving a lot like the once-in-a-century pathogen we’ve been worried about. I hope it’s not that bad, but we should assume it will be until we know otherwise. There are two reasons that Covid-19 is such a threat. First, it can kill healthy adults in addition to elderly people with existing health problems. The data so far suggest that the virus has a case fatality risk around 1%; this rate would make it many times more severe than typical seasonal influenza, putting it somewhere between the 1957 influenza pandemic (0.6%) and the 1918 influenza pandemic (2%).2",2020,"Gates, Bill",New England Journal of Medicine,,#2812,
,CZI,Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection,10.1073/pnas.1922083117,,32054787,,"The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV-induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.",2020,"de Wit, Emmie; Feldmann, Friederike; Cronin, Jacqueline; Jordan, Robert; Okumura, Atsushi; Thomas, Tina; Scott, Dana; Cihlar, Tomas; Feldmann, Heinz",Proc Natl Acad Sci U S A,3006564542,#984,
,CZI,The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus,10.1074/jbc.AC120.013056,,32094225,,"Antiviral drugs for managing infections with human coronaviruses are not yet approved, posing a serious challenge to current global efforts aimed at containing the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Remdesivir (RDV) is an investigational compound with a broad spectrum of antiviral activities against RNA viruses, including SARS-CoV and Middle East respiratory syndrome (MERS-CoV). RDV is a nucleotide analog inhibitor of RNA-dependent RNA polymerases (RdRps). Here, we co-expressed the MERS-CoV nonstructural proteins nsp5, nsp7, nsp8, and nsp12 (RdRp) in insect cells as a part a polyprotein to study the mechanism of inhibition of MERS-CoV RdRp by RDV. We initially demonstrated that nsp8 and nsp12 form an active complex. The triphosphate form of the inhibitor (RDV-TP) competes with its natural counterpart ATP. Of note, the selectivity value for RDV-TP obtained here with a steady-state approach suggests that it is more efficiently incorporated than ATP and two other nucleotide analogues. Once incorporated at position i, the inhibitor caused RNA synthesis arrest at position i+3. Hence, the likely mechanism of action is delayed RNA chain termination. The additional three nucleotides may protect the inhibitor from excision by the viral 3'-5' exonuclease activity. Together, these results help to explain the high potency of RDV against RNA viruses in cell-based assays.",2020,"Gordon, Calvin J.; Tchesnokov, Egor P.; Feng, Joy Y.; Porter, Danielle P.; Gotte, Matthias",J Biol Chem,2749506538,#1988,
,CZI,A time delay dynamic system with external source for the local outbreak of 2019-nCoV,10.1080/00036811.2020.1732357,,,,"How to model the 2019 CoronaVirus (2019-nCov) spread in China is one of the most urgent and interesting problems in applied mathematics. In this paper, we propose a novel time delay dynamic system with external source to describe the trend of local outbreak for the 2019-nCoV. The external source is introduced in the newly proposed dynamic system, which can be considered as the suspected people travel to different areas. The numerical simulations exhibit the dynamic system with the external source is more reliable than the one without it, and the rate of isolation is extremely important for controlling the increase of cumulative confirmed people of 2019-nCoV. Based on our numerical simulation results with the public data, we suggest that the local government should have some more strict measures to maintain the rate of isolation. Otherwise the local cumulative confirmed people of 2019-nCoV might be out of control.",2020,"Chen, Yu; Cheng, Jin; Jiang, Yu; Liu, Keji",Applicable Analysis,3005139704,#2331,
,CZI,A serological survey of canine respiratory coronavirus in New Zealand,10.1080/00480169.2019.1667282,,,,"Aims: To determine the seroprevalence of canine respiratory coronavirus (CRCoV) in New Zealand dogs, and to explore associations with age, sex, breed, month, and geographical region of sampling and reported presence of clinical signs suggestive of respiratory disease. Methods: A total of 1,015 canine serum samples were randomly selected from submissions to a diagnostic laboratory between March and December 2014, and were analysed for CRCoV antibodies using a competitive ELISA. Logistic regression analysis was used to determine associations between seroprevalence of CRCoV and breed category, age, sex, sampling month, region, and reported health status of dogs. Results: Overall, 538/1,015 (53.0%) samples were seropositive for CRCoV, with 492/921 (53.4%) positive dogs in the North Island and 46/94 (49%) in the South Island. Age of dog, sampling month, region, and presence of abnormal respiratory signs were included in the initial logistic regression model. Seroprevalence was higher in dogs aged >= 3 compared with <= 2 years (p<0.01). The lowest seroprevalence was observed in July (30/105; 28.5%) and August (32/100; 32%), and the highest in June (74/100; 74%). Seroprevalence in dogs from Auckland was higher than in dogs from the Hawkes Bay, Manawatu, Marlborough, and Waikato regions (p<0.05). Abnormal respiratory signs (coughing, nasal discharge, or sneezing) were reported for 28/1,015 (2.8%) dogs sampled. Seroprevalence for CRCoV tended to be higher among dogs with respiratory signs (67.9 (95% CI=47.6-83.4)%) than dogs with no reported respiratory signs (52.6 (95% CI=49.5-55.7)%). Conclusions: Serological evidence of infection with CRCoV was present in more than half of the dogs tested from throughout New Zealand. Differences in CRCoV seroprevalence between regions and lack of seasonal pattern indicate that factors other than external temperatures may be important in the epidemiology of CRCoV in New Zealand.",2020,"More, G. D.; Dunowska, M.; Acke, E.; Cave, N. J.",New Zealand Veterinary Journal,2972874979,#3840,
,CZI,Coronavirus disinfection in histopathology,10.1080/01478885.2020.1734718,,,,"The 2019 Coronavirus epidemic, provisionally called 2019-nCoV, was first identified in Wuhan, China, in persons exposed to a seafood or wet market. There is an international push to contain the virus and prevent its spread. It is feasible that potentially infectious samples may be received in histopathology laboratories for diagnosis. This technical note presents disinfection procedures and histotechnology processes that should alleviate the risk of infection to laboratory staff. Using data obtained from similar coronaviruses, e.g. severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), experts are confident that 70% ethanol and 0.1% sodium hypochlorite should inactivate the virus. Formalin fixation and heating samples to 56oC, as used in routine tissue processing, were found to inactivate several coronaviruses and it is believed that 2019-nCoV would be similarly affected.",2020,"Henwood, Anthony F.",Journal of Histotechnology,2080044878,#2831,
,CZI,"Emerging novel Coronavirus (2019-nCoV) - Current scenario, evolutionary perspective based on genome analysis and recent developments",10.1080/01652176.2020.1727993,,,,"Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade’s first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as “Public Health Emergency of International Concern” on January 30th, 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.",2020,"Malik, Yashpal Singh; Sircar, Shubhankar; Bhat, Sudipta; Sharun, Khan; Dhama, Kuldeep; Dadar, Maryam; Tiwari, Ruchi; Chaicumpa, Wanpen",Veterinary Quarterly,3004789303,#561,
,CZI,2019 novel coronavirus: an emerging global threat,10.1080/08998280.2020.1731272,,,,"The coronavirus (CoV) epidemic that began in China in December 2019 follows earlier epidemics of severe acute respiratory syndrome CoV in China and Middle East respiratory syndrome CoV in Saudi Arabia. The full genome of the 2019 novel coronavirus (2019-nCoV) has now been shared, and data have been gathered from several case series. As of February 11, 2020, there have been 45,182 laboratory-confirmed cases, the vast majority in China, with 1115 deaths, for an overall case-fatality rate of 2.5%. Cases have been confirmed in 27 countries. On average, each patient infects 2.2 other people. Symptomatic infection appears to predominantly affect adults, with a 5-day estimated incubation period between infection and symptom onset. The most common presenting symptoms are fever, cough, dyspnea, and myalgias and/or fatigue. All cases reported to date have shown radiographic evidence of pneumonia. 2019-nCoV is diagnosed by real-time reverse transcriptase polymerase chain reaction. Treatment is largely supportive, with regimens including antiviral therapy. Corticosteroids are not routinely recommended. Hand hygiene, prompt identification and isolation of suspect patients, and appropriate use of personal protective equipment are the most reliable methods to contain the epidemic",2020,"Columbus, Cristie; Brust, Karen B.; Arroliga, Alejandro C.",Baylor University Medical Center Proceedings,3003766409,#2319,
,CZI,The Effects of Social Media Use on Preventive Behaviors during Infectious Disease Outbreaks: The Mediating Role of Self-relevant Emotions and Public Risk Perception,10.1080/10410236.2020.1724639,,,,,2020,"Oh, Sang-Hwa; Lee, Seo Yoon; Han, Changhyun",Health Communication,2894148978,#1222,
,CZI,Effects of misleading media coverage on public health crisis: a case of the 2019 novel coronavirus outbreak in China,10.1080/13032917.2020.1730621,,,,"ABSTRACTThe coronavirus outbreak in Wuhan, China has sparked a global epidemic, which the World Health Organization declared a public health emergency of international concern on 31st January 2020 (Beijing time). This crisis has attracted intense media attention. Recently, some media outlets inappropriately labelled the coronavirus by race, using such headlines as ?Chinese virus pandemonium? and even suggesting ?China kids stay home.? The biased and misleading coverage presented via Western media channels has incited anger throughout the Chinese community and has placed undue stress upon Chinese individuals living outside China. This post-published review takes a tourism-focused perspective to examine findings from a quantitative study (Rodriguez-Seijas, Stohl, Hasin, & Eaton, 2015) published in 2015 in JAMA Psychiatry. The current paper highlights the potential impacts of misleading and biased media coverage on Chinese individuals? mental health. Specifically, this work considers perceived racial discrimination stemming from coronavirus as a public health crisis and the effects of such discrimination on individuals of Chinese heritage. Similarly imperative are pertinent effects on country image and destination image with respect to tourism marketing and tourist behaviour during times of crisis. By considering racism in the context of the coronavirus outbreak, this paper identifies potential avenues for relevant research in tourism and hospitality.",2020,"Wen, Jun; Aston, Joshua; Liu, Xinyi; Ying, Tianyu",Anatolia,2783117446,#1021,
,CZI,The global spread of 2019-nCoV: a molecular evolutionary analysis,10.1080/20477724.2020.1725339,,32048560,,"The global spread of the 2019-nCoV is continuing and is fast moving, as indicated by the WHO raising the risk assessment to high. In this article, we provide a preliminary phylodynamic and phylogeographic analysis of this new virus. A Maximum Clade Credibility tree has been built using the 29 available whole genome sequences of 2019-nCoV and two whole genome sequences that are highly similar sequences from Bat SARS-like Coronavirus available in GeneBank. We are able to clarify the mechanism of transmission among the countries which have provided the 2019-nCoV sequence isolates from their patients. The Bayesian phylogeographic reconstruction shows that the 2019-2020 nCoV most probably originated from the Bat SARS-like Coronavirus circulating in the Rhinolophus bat family. In agreement with epidemiological observations, the most likely geographic origin of the new outbreak was the city of Wuhan, China, where 2019-nCoV time of the most recent common ancestor emerged, according to molecular clock analysis, around November 25(th), 2019. These results, together with previously recorded epidemics, suggest a recurring pattern of periodical epizootic outbreaks due to Betacoronavirus. Moreover, our study describes the same population genetic dynamic underlying the SARS 2003 epidemic, and suggests the urgent need for the development of effective molecular surveillance strategies of Betacoronavirus among animals and Rhinolophus of the bat family.",2020,"Benvenuto, Domenico; Giovanetti, Marta; Salemi, Marco; Prosperi, Mattia; De Flora, Cecilia; Junior Alcantara, Luiz Carlos; Angeletti, Silvia; Ciccozzi, Massimo",Pathog Glob Health,3006367816,#795,
,CZI,Are we ready for the new fatal Coronavirus: scenario of Pakistan?,10.1080/21645515.2020.1724000,,,,"Scenario of Pakistan Pakistan, is the most affected countries, has experienced many diseases outbreaks and other disasters. Geographically and politically China and Pakistan are closely connected as shown in Figure 3. A large number of Chinese people are working in Pakistan on different developmental projects (China Pakistan Economic Corridor, Dams, Gawdar Port), and on the other hand many Pakistanis are residing in China carrying out their studies, business and jobs. The outbreak of coronavirus has appeared during the peak travel time when the Chinese from Pakistan and around the world are traveling to China, while the Pakistani community, especially students, are traveling back to Pakistan due to winter break. One of such case has been reported on 24 January 2020 after a person traveled from China to Pakistan on 21 January 2020 via Dubai and was diagnosed for 2019-nCoV on 24 January.3 However, the case was not notified officially by the government of Pakistan. In the depicted situation, the future is very alarming. After the ending of Chinese New Year celebrations, the Chinese will travel back to their jobs abroad, which may result in an outbreak of the fatal virus infection in Pakistan and other countries.",2020,"Ahmad, Tauseef; Khan, Muhammad; Khan, Fazal Mehmood; Hui, Jin",Human Vaccines & Immunotherapeutics,3005978769,#802,
,CZI,Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan,10.1080/22221751.2020.1719902,,,,"A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike's receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection. FAU - Chan, Jasper Fuk-Woo",,"Chan, J. F. Auid-Orcid https orcid org; Kok, K. H. Auid-Orcid https orcid org X.; Zhu, Z.; Chu, H.; To, K. K.; Yuan, S.; Yuen, K. Y.",,3003464757,#62,
,CZI,"An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies",10.1080/22221751.2020.1723441,,32005086,,,2020,"Jiang, S.; Du, L.; Shi, Z.",Emerging microbes & infections,3003788575,#136,
,CZI,RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak,10.1080/22221751.2020.1725399,,32020836,,"From December 2019, an outbreak of unusual pneumonia was reported in Wuhan with many cases linked to Huanan Seafood Market that sells seafood as well as live exotic animals. We investigated two patients who developed acute respiratory syndromes after independent contact history with this market. The two patients shared common clinical features including fever, cough, and multiple ground-glass opacities in the bilateral lung field with patchy infiltration. Here, we highlight the use of a low-input metagenomic next-generation sequencing (mNGS) approach on RNA extracted from bronchoalveolar lavage fluid (BALF). It rapidly identified a novel coronavirus (named 2019-nCoV according to World Health Organization announcement) which was the sole pathogens in the sample with very high abundance level (1.5% and 0.62% of total RNA sequenced). The entire viral genome is 29,881 nt in length (GenBank MN988668 and MN988669, Sequence Read Archive database Bioproject accession PRJNA601736) and is classified into β-coronavirus genus. Phylogenetic analysis indicates that 2019-nCoV is close to coronaviruses (CoVs) circulating in Rhinolophus (Horseshoe bats), such as 98.7% nucleotide identity to partial RdRp gene of bat coronavirus strain BtCoV/4991 (GenBank KP876546, 370 nt sequence of RdRp and lack of other genome sequence) and 87.9% nucleotide identity to bat coronavirus strain bat-SL-CoVZC45 and bat-SL-CoVZXC21. Evolutionary analysis based on ORF1a/1b, S, and N genes also suggests 2019-nCoV is more likely a novel CoV independently introduced from animals to humans.",2020,"Chen, Liangjun; Liu, Weiyong; Zhang, Qi; Xu, Ke; Ye, Guangming; Wu, Weichen; Sun, Ziyong; Liu, Fang; Wu, Kailang; Zhong, Bo; Mei, Yi; Zhang, Wenxia; Chen, Yu; Li, Yirong; Shi, Mang; Lan, Ke; Liu, Yingle",Emerg Microbes Infect,3005510968,#337,
,CZI,HIV-1 did not contribute to the 2019-nCoV genome,10.1080/22221751.2020.1727299,,32056509,,,2020,"Xiao, Chuan; Li, Xiaojun; Liu, Shuying; Sang, Yongming; Gao, Shou-Jiang; Gao, Feng",Emerg Microbes Infect,3006369964,#901,
,CZI,Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody,10.1080/22221751.2020.1729069,,32065055,,"The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 11,900 laboratory-confirmed human infections, including 259 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor-binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. These results suggest that CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, implying that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.",2020,"Tian, Xiaolong; Li, Cheng; Huang, Ailing; Xia, Shuai; Lu, Sicong; Shi, Zhengli; Lu, Lu; Jiang, Shibo; Yang, Zhenlin; Wu, Yanling; Ying, Tianlei",Emerg Microbes Infect,3003227632,#1100,
,CZI,Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes,10.1080/22221751.2020.1729071,,32065057,,"In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.",2020,"Zhang, Wei; Du, Rong-Hui; Li, Bei; Zheng, Xiao-Shuang; Yang, Xing-Lou; Hu, Ben; Wang, Yan-Yi; Xiao, Geng-Fu; Yan, Bing; Shi, Zheng-Li; Zhou, Peng",Emerg Microbes Infect,2040396289,#1080,
,CZI,Public's early response to the novel coronavirus-infected pneumonia,10.1080/22221751.2020.1732232,,32122250,,,2020,"Zhan, Siyi; Yang, Ying Ying; Fu, Chuanxi",Emerg Microbes Infect,3003668884,#3254,
,CZI,Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity,10.1080/22221751.2020.1732837,,32102625,,"The novel coronavirus (2019-nCoV) infection caused pneumonia. we retrospectively analyzed the virus presence in the pharyngeal swab, blood, and the anal swab detected by real-time PCR in the clinical lab. Unexpectedly, the 2109-nCoV RNA was readily detected in the blood (6 of 57 patients) and the anal swabs (11 of 28 patients). Importantly, all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity (p-value = 0.0001). Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage. However, the concentration of viral RNA in the anal swab (Ct value = 24 + 39) was higher than in the blood (Ct value = 34 + 39) from patient 2, suggesting that the virus might replicate in the digestive tract. Altogether, our results confirmed the presence of virus RNA in extra-pulmonary sites.",2020,"Chen, W.; Lan, Y.; Yuan, X.; Deng, X.; Li, Y.; Cai, X.; Li, L.; He, R.; Tan, Y.; Gao, M.; Tang, G.; Zhao, L.; Wang, J.; Fan, Q.; Wen, C.; Tong, Y.; Tang, Y.; Hu, F.; Li, F.; Tang, X.",Emerging microbes & infections,2487808280,#2765,
,CZI,No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2,10.1080/22221751.2020.1733440,,32102621,,,2020,"Liu, S. L.; Saif, L. J.; Weiss, S. R.; Su, L.",Emerging microbes & infections,2043547112,#2887,
,CZI,Treatment strategy for gastrointestinal tumor under the outbreak of novel coronavirus pneumonia in China,10.1089/lap.2017.0051,,,,"The outbreak of the novel coronavirus pneumonia (NCP) has become a public health emergency in China. Chinese authorities and health agencies had devoted great efforts to control this disease. As surgeons specialized in the treatment of gastrointestinal tumors, we should always be aware of the prevention for NCP and incorporate this awareness into every detail of clinical practice. For the patients with gastrointestinal tumors, pre-admission screening should be done in order to rule out NCP. Real-time RT-PCR panel and chest CT scan should be conducted for patients with fever (>37.3℃), travel history to Hubei Province within 14 days, or contact history with residents from Wuhan district within 14 days. Prevention measures for both medical staffs and the screen-negative admitted patients should also be enhanced because false negative is possible. Medical instruments should be properly discarded or disinfected according to standardized procedures established by the local center for disease control and prevention (CDC). Surgical operation should be reduced at a minimal level to prevent cross infection in this special period.Surgical intervention for benign tumor should be postponed. For malignant tumor, multidisciplinary therapy (MDT) is recommended and non-surgical anti-tumor therapy should be selected with higher priority. Neoadjuvant therapy is highly recommended for gastrointestinal cancer at advanced stages that meet the indications of NCCN guideline (gastric cancer T stage ≥ 2/rectal cancer T stage ≥ 3/unresectable colon cancer). Gastric or esophagogastricjunction (EGJ) malignant tumor with obstruction can be managed with gastric tube decompression or stent placement to relieve the symptoms. Transnasal enteral feeding tube intubation/percutaneous endoscopic gastrostomy could be adopted to ensure enteral nutrition supply. For colorectal malignancy with simple intestinal obstruction, stent placement can achieve a high success rate, which not only helps avoid emergency surgery, but also creates a better condition for subsequent surgery. Transcatheter arterial embolization for hemostasis is an alternative choice for gastrointestinal tumor with bleeding. However, emergency operation still must be performed for patients with acute uncontrolled bleeding, obstruction or after other alternative treatment measures fail. All cases with suspicious or confirmed with NCP must be reported to the local CDC department. All invasive intervention must be performed in a designated isolation area. Tertiary prevention measure must be adopted for all anesthetists with additional face mask or medical goggle protection to prevent respiratory droplet transmission. Preventive enterostomy is preferable in lower digestive tract surgery. Thoroughly disinfecting the operating room after surgery is necessary. Fever after surgery must be carefully differentiated whether it's caused by post-surgery abdominal infection/inflammation or NCP. Single-room isolation and related examinations should be performed according to the standard procedures. We believe that with the unprecedentedly joint efforts of doctors and patients, we will eventually win this war against NCP.",2020,"CHEN, Yonghe",Chinese Journal of Gastrointestinal Surgery,2606110885,#2332,
,CZI,Imported Novel Coronavirus Infections: Observation on Active and Passive Case Detection in Thailand,10.1089/pop.2020.0014,,,,"In December 2019, a viral disease – the novel coronavirus – emerged in China and spread widely.1 At present, the disease has already exported to many countries,2 and is becoming an important public health problem. Thailand is a Southeast Asian country that has many international flights connecting to China and there are already imported cases of the disease in Thailand. The first ex-China case of the new disease was detected in Thailand. We would like to share observations on the spread of this disease in Thailand. To date (24 January 2020), there are imported cases of novel coronavirus infections in Thailand. Of these cases, 1 patient is a Thai who returned from tourism activity in China and the others are 4 Chinese tourists. Focusing on disease detection, 4 patients were detected at health screening points at immigration posts at international airports. The Thai patient visited the physician herself after developing a fever upon returning to Thailand. Of interest, during the period of disease outbreak, active screening is done at Thai international airports and 21,374 travelers have already been screened. Active screening can detect 80% of imported cases; 20% are detected passively. Based on these data, it has been demonstrated that active screening at the airport is still a good method for detecting new emerging disease but it cannot provide 100% efficacy in case detection. The health-related self-concern of the patient is also important to help with passive case detection. Therefore, promotion of health knowledge concerning the new disease is very important for the international traveler.",2020,"Sookaromdee, Pathum; Wiwaniveitkit, Viroj",Population Health Management,2061002138,#3117,
,CZI,Anesthesia Procedure of Emergency Operation for Patients with Suspected or Confirmed COVID-19,10.1089/sur.2020.040,,32096692,,,2020,"Wen, Xianjie; Li, Yiqun",Surg Infect (Larchmt),2364907110,#1917,
,CZI,Three Emerging Coronaviruses in Two Decades,10.1093/ajcp/aqaa029,,32053148,,"In the past two decades, the world has seen three coronaviruses emerge and cause outbreaks that have caused considerable global health consternation. Coronaviruses are enveloped, nonsegmented, single-stranded, positive-sense RNA viruses that have a characteristic appearance on electron microscopy negative staining Image 1. As a matter of fact, the characteristic electron microscopy appearance was the clue to amplify and sequence nucleic acids from Dr Urbani’s (one of the health care providers who died of severe acute respiratory syndrome [SARS] in 2003) respiratory specimen using a consensus coronavirus primer.1 The sequence of the virus was significantly different from other coronaviruses known to cause human disease at the time. The virus was ultimately named SARS-CoV, as febrile patients had severe acute respiratory syndrome and could present with pneumonia and lower respiratory symptoms such as cough and dyspnea.2 The SARS-CoV outbreak started in Guangdong, China, and spread to many countries in Southeast Asia, North America, Europe, and South Africa. Transmission was primarily person to person through droplets that occurred during coughing or sneezing, through personal contact (shaking hands), or by touching contaminated surfaces. Of note, health professionals were particularly at risk of acquiring the disease, as transmission also occurred if isolation precautions were not followed and during certain procedures. The last case of SARS-CoV occurred in September 2003, after having infected over 8,000 persons and causing 774 deaths with a case fatality rate calculated at 9.5%.",2020,"Guarner, Jeannette",Am J Clin Pathol,3006290567,#879,
,CZI,Characteristics of peripheral blood leukocyte differential counts in patients with COVID-19,10.1093/ajcp/aqw151.021,,32114745,,"To investigate the early changes of peripheral blood leukocyte differential counts in patients with COVID-19. Ten patients with COVID-19 and 30 patients with other viral pneumonia (non-COVID-19) admitted to Shanghai Jiao Tong University Affiliated Sixth People's Hospital and Jinshan Branch Hospital from January 22 to February 17, 2020 were enrolled in this study. The differential counts of white blood cells were analyzed. Patients in COVID-19 group showed relatively lower absolute white blood cell (WBC) count 4.95(3.90,6.03)×10(9)/L, lymphocyte absolute count 1.20(0.98,1.50)×10(9)/L and eosinophil absolute count 0.01(0.01,0.01)×10(9)/L. Leukopenia developed in two patients(2/10), lymphocytopenia also in two patients(2/10). Seven over ten patients presented with eosinophil cytopenia. In non-COVID-19 group, absolute WBC count was 8.20 (6.78,9.03) ×10(9)/L (P<0.001), lymphocyte absolute count 1.75(1.20,2.53)×10(9)/L(P=0.036), eosinophil absolute count 0.02(0.01,0.03)×10(9)/L(P=0.05). Lymphocytopenia occurred in (16.7%) patients, eosinophil cytopenia in 16.7% patients too. In conclusion, leukopenia, lymphocytopenia and eosinophil cytopenia are more common in COVID-19 patients than those in non- COVID-19 patients.",2020,"Li, Y. X.; Wu, W.; Yang, T.; Zhou, W.; Fu, Y. M.; Feng, Q. M.; Ye, J. M.",Zhonghua Nei Ke Za Zhi,2588578963,#3058,
,CZI,Selection and Use of Respiratory Protection by Healthcare Workers to Protect from Infectious Diseases in Hospital Settings,10.1093/annweh/wxaa020,,,,"Abstract Objectives Infection control policies and guidelines recommend using facemasks and respirators to protect healthcare workers (HCWs) from respiratory infections. Common types of respirators used in healthcare settings are filtering facepiece respirators (FFRs) and powered air-purifying respirators (PAPRs). Aims of this study were to examine the current attitudes and practices of HCWs regarding the selection and use of respiratory protection and determine the acceptability of a novel PAPR. Methods In-depth interviews were undertaken with 20 HCWs from a large tertiary hospital in Sydney, Australia. Participants were fit tested with a lightweight tight-fitting half-facepiece PAPR (CleanSpace2™ Power Unit, PAF-0034, by CleanSpace Technology®) using the TSI™ Portacount quantitative fit test method. Results Interview results showed that HCWs had a limited role in the selection and use of facemasks and respirators and had been using the devices provided by the hospital. The majority of subjects had no knowledge of hospital policy for the use of facemasks and respirators, had not been trained on the use of respirators, and had not been fit tested previously. Compliance with the use of facemasks and respirators was perceived as being low and facemasks and respirators were typically used only for short periods of time. All 20 participants were successfully fit tested to the CleanSpace2™ PAPR (overall geometric mean fit factor—6768). According to the exit surveys, CleanSpace2™ PAPRs were easy to don (14/20) and doff (15/20) and comfortable to wear (14/20). Most participants believed that PAPRs provide higher protection, comfort and reusability over N95 FFR and can be used during pandemics and other high-risk situations. Conclusions HCWs should be aware of infection control policies and training should be provided on the correct use of respiratory protective devices. PAPRs can be used in hospital settings to protect HCWs from certain highly infectious and emerging pathogens, however, HCWs require adequate training on storage, use, and cleaning of PAPRs.",2020,"Chughtai, Abrar Ahmad; Seale, Holly; Rawlinson, William D.; Kunasekaran, Mohana; Macintyre, C. Raina",Annals of Work Exposures and Health,2800868152,#5147,
,CZI,Emergency management practice of novel coronavirus pneumonia in designated hospitals,10.1093/bja/aew177,,,,"At present, we are fighting against the outbreak of novel coronavirus pneumonia (NCP) in China. For the purposes of diagnosis and treatment of NCP patients, Hangzhou Xixi Hospital, as a designated hospital, make available the wards quickly, initiated the management system of public health emergencies, and established a 'tolerate admission- strict discharge' patients management program. Meanwhile, the hospital has established an emergency supply and coordinated distribution mechanism for medical protection materials, and a full-system and multi-model training system, ensuring smooth progress of the diagnosis and treatment work.",2020,"CHEN, Changgui; ZHANG, Songping; HUANG, Xiaohua; HUANG, Jinsong; CAI, Zhaobin",Chinese Journal of Hospital Administration,2480878409,#2341,
,CZI,Origin and evolution of the 2019 novel coronavirus,10.1093/cid/ciaa112,,,,"As of today, the intermediate host of 2019-nCoV has not been determined. Considering that intermediate hosts are generally mammals [5], they are likely the living mammals sold in the South China seafood market. Therefore, strengthening the monitoring of wild mammals is an urgent measure to prevent similar viruses from infecting humans in the future. More than 1,000 confirmed cases have been reported in China. The number of provinces and cities in China as well as other Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa112/5721420 by World Health Organization user on 06 February 2020 countries with confirmed cases are steadily increasing. It is necessary to further strengthen the monitoring to ensure that it will not cause diseases like Global Outbreak of 2003 SARS.",2020,"Liangsheng Zhang, Fu-ming Shen, Fei Chen, Zhenguo Lin","Clinical Infectious Diseases,",3004748218,#248,
,CZI,Consistent detection of 2019 novel coronavirus in saliva,10.1093/cid/ciaa149,,,,"The 2019-novel-coronavirus (2019-nCoV) was detected in the self-collected saliva of 91.7% (11/12) of patients. Serial saliva viral load monitoring generally showed a declining trend. Live virus was detected in saliva by viral culture. Saliva is a promising non-invasive specimen for diagnosis, monitoring, and infection control in patients with 2019-nCoV infection.",2020,"To, Kelvin Kai-Wang; Tsang, Owen Tak‐Yin; Chik-Yan Yip, Cyril; Chan, Kwok-Hung; Wu, Tak-Chiu; Chan, Jacky M. C.; Leung, Wai-Shing; Chik, Thomas Shiu-Hong; Choi, Chris Yau-Chung; Kandamby, Darshana H.; Lung, David Christopher; Tam, Anthony Raymond; Poon, Rosana Wing-Shan; Fung, Agnes Yim-Fong; Hung, Ivan Fan-Ngai; Cheng, Vincent Chi-Chung; Chan, Jasper Fuk-Woo; Yuen, Kwok-Yung",Clinical Infectious Diseases,3005690553,#724,
,CZI,De-isolating COVID-19 Suspect Cases: A Continuing Challenge,10.1093/cid/ciaa179,,,,"As of 15 February 2020, Singapore had screened a total of 991 suspect cases for COVID-19, of which 72 cases tested positive, 812 cases tested negative, while the remaining 107 had pending results.(1) Besides optimising sample type to increase yield, (2) the challenge in clinical management of suspect cases lies in deciding whether they may be de-isolated or if further isolation and repeat testing is required. No single indicator may be effectively used to decide on de-isolation of a suspect case. In our series of positive cases, samples from one suspect case only returned positive on the fifth repeated sample (nasopharyngeal swab), on the seventh day of clinical illness. Current evidence suggests that transmission of COVID-19 may be possible even from asymptomatic contacts,(3) and polymerase chain reaction (PCR) testing may not return positive initially. (4) Our suspect case was kept isolated because of a high index of clinical suspicion, with a clinically compatible illness and history of close contact with a laboratory-proven COVID-19 case. While multiplex respiratory virus panels, in general, may be helpful in the evaluation of other viral acute respiratory infections (ARIs), even the detection of an alternate respiratory pathogen may not definitively exclude COVID-19 infection. Dual infections can occur in 10- 20% of viral acute respiratory infections, as has been reported with SARS-CoV and MERSCoV. (5) In our case series, one patient with confirmed COVID-19 by nasopharyngeal aspirate also exhibited clinical symptoms compatible with dengue fever. This was laboratory confirmed by dengue NS1 antigen test. (PL Lim, personal communication).",2020,"Tay, Jun-Yang; Lim, Poh Lian; Marimuthu, Kalisvar; Sadarangani, Sapna Pradip; Ling, Li Min; Ang, Brenda Sze Peng; Chan, Monica; Leo, Yee-Sin; Vasoo, Shawn",Clinical Infectious Diseases,1556287221,#2378,
,CZI,A Case Series of children with 2019 novel coronavirus infection: clinical and epidemiological features,10.1093/cid/ciaa198,,32112072,,We first described the 2019 novel coronavirus infection in 10 children occurring in areas other than Wuhan. The coronavirus diseases in children are usually mild and epidemiological exposure is a key clue to recognize pediatric case. Prolonged virus shedding is observed in respiratory tract and feces at the convalescent stage.,2020,"Cai, J.; Xu, J.; Lin, D.; Yang, Z.; Xu, L.; Qu, Z.; Zhang, Y.; Zhang, H.; Jia, R.; Liu, P.; Wang, X.; Ge, Y.; Xia, A.; Tian, H.; Chang, H.; Wang, C.; Li, J.; Wang, J.; Zeng, M.",Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,3004790666,#2743,
,CZI,Clinical Characteristics of Imported Cases of COVID-19 in Jiangsu Province: A Multicenter Descriptive Study,10.1093/cid/ciaa199,,32109279,,"BACKGROUND: We aimed to report the clinical characteristics of imported coronavirus disease-19 (COVID-19) in Jiangsu Province. METHODS: We retrospectively investigated the clinical, imaging, and laboratory characteristics of confirmed cases of COVID-19 with WHO interim guidance in three Grade A hospitals of Jiangsu from Jan 22 to Feb 14, 2020. Real time RT-PCR was used to detect the new coronavirus in respiratory samples. RESULTS: Of the 80 patients infected with COVID-19, 41 patients were female, with a median age of 46.1 years. Except for 3 severe patients, the rest of the 77 patients exhibited mild or moderate symptoms. 9 patients were unconfirmed until a third-time nucleic acid test. 38 cases had a history of chronic diseases. The main clinical manifestations of the patients were fever and cough, which accounted for 63 cases (78.75%) and 51 cases (-63.75%) respectively. Only 3 patients (3.75%) showed liver dysfunction. Imaging examination showed that 55 patients (-68.75%) showed abnormal, 25 cases (31.25%) had no abnormal density shadow in the parenchyma of both lungs. Up to now, 21 cases were discharged from the hospital, and no patient died. The average length of stay for discharged patients was 8 days. CONCLUSIONS: Compared with the cases in Wuhan, the cases in Jiangsu exhibited mild or moderate symptoms and no obvious gender susceptivity. The proportion of patients having liver dysfunction and abnormal CT imaging was relatively lower than that of Wuhan. Notably, infected patients may be falsely excluded based on two consecutively negative respiratory pathogenic nucleic acid test results.",2020,"Wu, J.; Liu, J.; Zhao, X.; Liu, C.; Wang, W.; Wang, D.; Xu, W.; Zhang, C.; Yu, J.; Jiang, B.; Cao, H.; Li, L.",Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,3005679569,#2978,
,CZI,A case of 2019 Novel Coronavirus in a pregnant woman with preterm delivery,10.1093/cid/ciaa200,,32119083,,We presented a case of a 30-week pregnant woman with COVID-19 delivering a healthy baby with no evidence of COVID-19.,2020,"Wang, Xiaotong; Zhou, Zhiqiang; Zhang, Jianping; Zhu, Fengfeng; Tang, Yongyan; Shen, Xinghua",Clin Infect Dis,2066024373,#3279,
,CZI,A Well Infant with Coronavirus Disease 2019 (COVID-19) with High Viral Load,10.1093/cid/ciaa201,,,,A well 6-month-old infant with coronavirus disease 2019 (COVID-19) had persistently positive nasopharyngeal swabs to day 16 of admission. This case highlights the difficulties in establishing the true incidence of COVID-19 as asymptomatic individuals can excrete the virus. These patients may play important roles in human-to-human transmission in the community.,2020,"Kam, Kai-qian; Yung, Chee Fu; Cui, Lin; Lin Tzer Pin, Raymond; Mak, Tze Minn; Maiwald, Matthias; Li, Jiahui; Chong, Chia Yin; Nadua, Karen; Tan, Natalie Woon Hui; Thoon, Koh Cheng",Clinical Infectious Diseases,3005657121,#2851,
,CZI,Genomic diversity of SARS-CoV-2 in Coronavirus Disease 2019 patients,10.1093/cid/ciaa203,,,,"A novel coronavirus (SARS-CoV-2) has infected more than 75,000 individuals and spread to over 20 countries. It is still unclear how fast the virus evolved and how the virus interacts with other microorganisms in the lung.We have conducted metatranscriptome sequencing for the bronchoalveolar lavage fluid of eight SARS-CoV-2 patients, 25 community-acquired pneumonia (CAP) patients, and 20 healthy controls.The median number of intra-host variants was 1-4 in SARS-CoV-2 infected patients, which ranged between 0 and 51 in different samples. The distribution of variants on genes was similar to those observed in the population data (110 sequences). However, very few intra-host variants were observed in the population as polymorphism, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intra-host variants in a person-to-person spread, the risk should not be overlooked. The microbiota in SARS-CoV-2 infected patients was similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria.SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intra-host variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral evolution in the population and associated clinical changes.",2020,"Shen, Zijie; Xiao, Yan; Kang, Lu; Ma, Wentai; Shi, Leisheng; Zhang, Li; Zhou, Zhuo; Yang, Jing; Zhong, Jiaxin; Yang, Donghong; Guo, Li; Zhang, Guoliang; Li, Hongru; Xu, Yu; Chen, Mingwei; Gao, Zhancheng; Wang, Jianwei; Ren, Lili; Li, Mingkun",Clinical Infectious Diseases,3006645647,#3950,
,CZI,A glimpse into the origins of genetic diversity in SARS-CoV-2,10.1093/cid/ciaa213,,32129842,,,2020,"Wertheim, Joel O.",Clin Infect Dis,2076855096,#4411,
,CZI,2019 novel coronavirus is undergoing active recombination,10.1093/cid/ciaa219,,,,"The 2019 novel coronavirus (2019-nCoV) outbreak in Wuhan since December 2019 [1] has quickly spread to twenty-five countries [2], caused more than 44,000 cases and 1,000 deaths so far [3]. The fast sharing of 2019-nCoV genomes in GISAID (https://www.gisaid.org) provides a valuable dataset for 2019-nCoV haplotype network analysis, which is crucial for transmission and evolutionary track surveillance and secondary outbreak prevention. We called single-nucleotide variations (SNVs) for all the 84 2019-nCov genomes in GISAID using MN908947 as the reference. Genomes with same SNVs are grouped into a haplotype (shown as a pie chart node in Fig. 1, see Tab. S1 for the accessions), then the network is constructed using the median join [4] method in popART [5]. We found the 2019-nCoV haplotype network has obvious characteristics of single origin from haplotype hap_011: first, the network is star-like, centralized on the haplotype hap_011; second, hap_011 has the largest sample size and majority of the samples are from Hubei province—where outbreak originated (Tab. S1); third, most of satellite haplotypes are also from Hubei (Fig. 1); fourth, the average collection dates of hap_011 (has 0 mutation relative to MN908947) is earlier than all other mutation groups (Fig. S1). The single origin of 2019-nCov indicates a persistent animal to human transmission is unlikely, otherwise, multiple nodes with above characteristics should be observed.",2020,"Yi, Huiguang",Clinical Infectious Diseases,2954504078,#4262,
,CZI,Racing towards the development of diagnostics for a novel coronavirus (2019-nCoV),10.1093/clinchem/hvaa038,,32031590,,,2020,"Dennis Lo, Y. M.; Chiu, Rossa W. K.",Clin Chem,3005417802,#544,
,CZI,"Emergence of a Novel Coronavirus Disease (COVID-19) and the Importance of Diagnostic Testing: Why Partnership between Clinical Laboratories, Public Health Agencies, and Industry Is Essential to Control the Outbreak",10.1093/clinchem/hvaa071,,,,,2020,"Binnicker, Matthew J.",Clinical Chemistry,1963699916,#1412,
,CZI,Expert consensus on emergency surgery management for traumatic orthopedics under prevention and control of novel coronavirus pneumonia,10.1093/ejcts/ezw326,,,,"Since December 2019, novel coronavirus pneumonia (NCP) has been reported in Wuhan, Hubei Province, and spreads rapidly to all through Hubei Province and even to the whole country. The virus is 2019 novel coronavirus (2019-nCoV), never been seen previously in human, but all the population is generally susceptible. The virus spreads through many ways and is highly infectious, which brings great difficulties to the prevention and control of NCP. Based on the needs of orthopedic trauma patients for emergency surgery and review of the latest NCP diagnosis and treatment strategy and the latest principles and principles of evidence-based medicine in traumatic orthopedics, the authors put forward this expert consensus to systematically standardize the clinical pathway and protective measures of emergency surgery for orthopedic trauma patients during prevention and control of NCP and provide reference for the emergency surgical treatment of orthopedic trauma patients in hospitals at all levels.",2020,"LIU, Jing; LI, Hui; ZHOU, Wu; LIU, Guohui; ZHANG, Yingze; JIANG, Baoguo; TANG, Peifu; LIU, Guodong; WU, Xinbao; YUAN, Zhi; ZHOU, Fang; WANG, Tianbing; FU, Zhongguo; HOU, Zhiyong; SU, Jiacan; YU, Bin; SHAO, Zengwu; XIA, Tian; XIONG, Liming; FANG, Yue; WANG, Guanglin; LIN, Peng; CHEN, Yanxi; NI, Jiangdong; YANG, Lei; WANG, Dongliang; HE, Chengjian; LIU, Ximing; CHE, Biao; LI, Yaming; WANG, Junwen; CHEN, Ming; ZHAO, Meng; CAO, Faqi; SUN, Yun; MI, Bobin; LIU, Mengfei; XIONG, Yuan; XUE, Hang; HU, Liangcong; HU, Yiqiang; CHEN, Lang; YAN, Chenchen",Chinese Journal of Trauma,2572688892,#2186,
,CZI,Coronaviruses: a paradigm of new emerging zoonotic diseases,10.1093/femspd/ftaa006,,,,"A novel type of coronavirus (2019-nCoV) infecting humans appeared in Wuhan, China, at the end of December 2019. Since the identification of the outbreak the infection quickly spread involving in one month more than 31,000 confirmed cases with 638 death. Molecular analysis suggest that 2019-nCoV could be originated from bats after passaging in intermediate hosts, highlighting the high zoonotic potential of coronaviruses.",2020,"Salata, Cristiano; Calistri, Arianna; Parolin, Cristina; Palù, Giorgio",Pathogens and Disease,2097158803,#1116,
,CZI,"The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned?",10.1093/ije/dyaa033,,,,"To provide an overview of the three major deadly coronaviruses and identify areas for improvement of future preparedness plans, as well as provide a critical assessment of the risk factors and actionable items for stopping their spread, utilizing lessons learned from the first two deadly coronavirus outbreaks, as well as initial reports from the current novel coronavirus (COVID-19) epidemic in Wuhan, China.Utilizing the Centers for Disease Control and Prevention (CDC, USA) website, and a comprehensive review of PubMed literature, we obtained information regarding clinical signs and symptoms, treatment and diagnosis, transmission methods, protection methods and risk factors for Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) and COVID-19. Comparisons between the viruses were made.Inadequate risk assessment regarding the urgency of the situation, and limited reporting on the virus within China has, in part, led to the rapid spread of COVID-19 throughout mainland China and into proximal and distant countries. Compared with SARS and MERS, COVID-19 has spread more rapidly, due in part to increased globalization and the focus of the epidemic. Wuhan, China is a large hub connecting the North, South, East and West of China via railways and a major international airport. The availability of connecting flights, the timing of the outbreak during the Chinese (Lunar) New Year, and the massive rail transit hub located in Wuhan has enabled the virus to perforate throughout China, and eventually, globally.We conclude that we did not learn from the two prior epidemics of coronavirus and were ill-prepared to deal with the challenges the COVID-19 epidemic has posed. Future research should attempt to address the uses and implications of internet of things (IoT) technologies for mapping the spread of infection.",2020,"Peeri, Noah C.; Shrestha, Nistha; Rahman, Md Siddikur; Zaki, Rafdzah; Tan, Zhengqi; Bibi, Saana; Baghbanzadeh, Mahdi; Aghamohammadi, Nasrin; Zhang, Wenyi; Haque, Ubydul",International Journal of Epidemiology,3006113744,#1525,
,CZI,A familial cluster of infection associated with the 2019 novel coronavirus indicating potential person-to-person transmission during the incubation period,10.1093/infdis/jiaa077,,,,"An ongoing outbreak of pneumonia associated with 2019 novel coronavirus (2019-nCoV) was reported in China. It is unclear if the infectivity exists during the incubation period, although a person-to-person transmission has been reported in previous studies. We report the epidemiological features of a familial cluster of four patients in Shanghai, of which one was 88 years old man with moving difficulties and was only exposed to his asymptomatic family members who developed symptoms later. The epidemiological evidence has shown a potential transmission of the 2019-nCoV during the incubation period.",2020,"Yu, Ping; Zhu, Jiang; Zhang, Zhengdong; Han, Yingjun; Huang, Lihong",The Journal of Infectious Diseases,3002539152,#1085,
,CZI,Evaluation of serologic and antigenic relationships between middle eastern respiratory syndrome coronavirus and other coronaviruses to develop vaccine platforms for the rapid response to emerging coronaviruses,10.1093/infdis/jit609,,,,"Background: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs.Methods: Using synthetic genomics and Venezuelan equine encephalitis virus replicons (VRPs) expressing spike and nucleocapsid proteins from MERS-CoV and other human and bat CoVs, we characterize the antigenic responses (using Western blot and enzyme-linked immunosorbent assay) and serologic responses (using neutralization assays) against 2 MERS-CoV isolates in comparison with those of other human and bat CoVs.Results: Serologic and neutralization responses against the spike glycoprotein were primarily strain specific, with a very low level of cross-reactivity within or across subgroups. CoV N proteins within but not across subgroups share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using a convalescent-phase serum specimen from a patient infected with MERS-CoV (NA 01) and human antiserum against SARS-CoV, human CoV NL63, and human CoV OC43.Conclusions: Vaccine design for emerging CoVs should involve chimeric spike protein containing neutralizing epitopes from multiple virus strains across subgroups to reduce immune pathology, and a diagnostic platform should include a panel of nucleocapsid and spike proteins from phylogenetically distinct CoVs.",2014,"Agnihothram, Sudhakar; Gopal, Robin; Yount Jr, Boyd L.; Donaldson, Eric F.; Menachery, Vineet D.; Graham, Rachel L.; Scobey, Trevor D.; Gralinski, Lisa E.; Denison, Mark R.; Zambon, Maria; Baric, Ralph S.; Yount, Boyd L., Jr.",Journal of Infectious Diseases,2100790445,#2452,
,CZI,"The New Coronavirus, the Current King of China",10.1093/jpids/piaa018,,,,"Coronaviruses are respiratory viruses whose appearance on electron microscopy looks like tiny crowns (Figure 1). The first coronaviruses discovered were the cause of pediatric and adult respiratory infections that were not particularly dangerous. One study from Vanderbilt found coronavirus in about 5% of samples from upper respiratory illness and 8% from lower respiratory illness [1]. Most clinically significant coronavirus infections have been found in children < 2 years of age, as reviewed in this journal in 2009 [2], although adults also might suffer severe infections [3, 4]. This was the picture as late as 2018: a group of respiratory viruses that could cause serious illness in the very young, but with negligible mortality [5, 6].",2020,"Plotkin, Stanley A.",Journal of the Pediatric Infectious Diseases Society,3001897055,#1519,
,CZI,"Pneumonia of Unknown Etiology in Wuhan, China: Potential for International Spread Via Commercial Air Travel",10.1093/jtm/taaa008,,,,"There is currently an outbreak of a pneumonia of unknown etiology in Wuhan, China. While there are still several unanswered questions, we evaluate the potential for international dissemination of this disease via commercial air travel should the outbreak continue.",2020,"Bogoch, I. I.; Watts, A.; Thomas-Bachli, A.; Huber, C.; Kraemer, M. U. G.; Khan, K.",Journal of travel medicine,2999612210,#4,
,CZI,Travelers Give Wings to Novel Coronavirus (2019-nCoV),10.1093/jtm/taaa015,,,,,2020,"Wilson, Mary E.; Chen, Lin H.",Journal of Travel Medicine,3004555297,#260,
,CZI,"Isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus (2019-nCoV) outbreak",10.1093/jtm/taaa020,,,,Community containment includes measures that range from increasing social distancing to coummunity-wide quarantine. Whether these measures will be sufficient to control 2019-ncov depends on addressing some unanswered questions.,2020,"Wilder-Smith, A.; Freedman, D. O.",Journal of Travel Medicine,3006533361,#850,
,CZI,Solidarity with China as it holds the global front line during COVID-19 outbreak,10.1093/jtm/taaa027,,32125432,,,2020,"Lin, Leesa",J Travel Med,2766093046,#3352,
,CZI,Saudi Arabia`s measures to curb the COVID-19 outbreak: temporary suspension of the Umrah pilgrimage,10.1093/jtm/taaa029,,32109274,,,2020,"Ebrahim, S. H.; Memish, Z. A.",Journal of travel medicine,2516540472,#2796,
,CZI,The pandemic of social media panic travels faster than the COVID-19 outbreak,10.1093/jtm/taaa031,,32125413,,,2020,"Depoux, Anneliese; Martin, Sam; Karafillakis, Emilie; Bsd, Raman Preet; Wilder-Smith, Annelies; Larson, Heidi",J Travel Med,1501709847,#3421,
,CZI,On the origin and continuing evolution of SARS-CoV-2,10.1093/nsr/nwaa036,,,,"The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Although the L type (∼70%) is more prevalent than the S type (∼30%), the S type was found to be the ancestral version. Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020. Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure. These findings strongly support an urgent need for further immediate, comprehensive studies that combine genomic data, epidemiological data, and chart records of the clinical symptoms of patients with coronavirus disease 2019 (COVID-19).",2020,"Tang, Xiaolu; Wu, Changcheng; Li, Xiang; Song, Yuhe; Yao, Xinmin; Wu, Xinkai; Duan, Yuange; Zhang, Hong; Wang, Yirong; Qian, Zhaohui; Cui, Jie; Lu, Jian",National Science Review,2377437096,#3293,
,CZI,In this issue of Occupational Medicine,10.1093/occmed/kqaa028,,,,"The recent COVID-19 outbreak in Wuhan city (Hubei Province of central China), presents significant public health challenges not only in china but across all affected countries worldwide. Koh [1] succinctly describes what coronaviruses are, and outlines six known species associated with human illnesses. The article also describes countries of origin of previous coronavirus disease outbreaks and reports number of known fatalities with associated case-fatality rates. Occupations implicated in the current COVID-19 outbreak are detailed and groups at high risk of contracting the infection e.g. healthcare workers highlighted. Social stigmatisation associated with COVID-19 is explored and suggested measures to contain the infection discussed.",2020,"Jackson-Koku, Gordon",Occupational Medicine,2891398425,#1623,
,CZI,Changes of CT Findings in a 2019 Novel Coronavirus (2019-nCoV) pneumonia patient,10.1093/qjmed/hcaa038,,32073631,,,2020,"Fang, Xin; Zhao, Ming; Li, Shuang; Yang, Lanqing; Wu, Bing",QJM,3004511262,#1312,
,CZI,Novel coronavirus (2019-nCoV): Update on 3rd Coronavirus Outbreak of 21st Century,10.1093/qjmed/hcaa081,,32125418,,,2020,"Sahu, Kamal Kant; Mishra, Ajay Kumar; Lal, Amos",QJM,3000883359,#3309,
,CZI,Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel coronavirus pneumonia,10.1097/BPO.0b013e3182840de2,,,,"A novel coronavirus pneumonia (NCP) epidemic has occurred in Wuhan, Hubei Province since December 2019, caused by a novel coronavirus (2019-nCoV) never been seen previously in human. China has imposed the strictest quarantine and closed management measures in history to control the spreading of the disease. However, severe trauma can still occur in the NCP patients. In order to standardize the emergency treatment and the infection prevention and control of severe trauma patients with hidden infection, suspected or confirmed infection of 2019-nCoV, Trauma Surgery Branch of Chinese Medical Doctors' Association organized this expert consensus. The consensus illustrated the classification of the NCP patients, severe trauma patients in need of emergency surgery, emergency surgery type, hierarchical protection for medical personnel and treatment places. Meanwhile, the consensus standardized the screening, injury severity evaluation, emergency surgical treatment strategy and postoperative management strategy of severe trauma patients during the epidemic period of NCP, providing a basis for the clinical treatment of such kind of patients.",2020,"LI, Yang; LI, Zhanfei; MAO, Qingxiang; LIU, Ding; ZHANG, Letian; YANG, Fan; XIE, Yu; ZHOU, Siru; ZHANG, Huayu; AI, Shanmu; TANG, Hao; ZHONG, Qiu; GUO, Qingshan; WANG, Yaoli; ZHANG, Weiguo; CHEN, Liyong; BAI, Xiangjun; ZHANG, Lianyang",Chinese Journal of Trauma,1976983792,#2202,
,CZI,Epidemiological and clinical characteristics of novel coronavirus infection in children: Thoughts on the diagnostic criteria of suspected cases outside Hubei Province,10.1097/INF.0b013e31806211bf,,,,"Objective To improve the diagnostic criteria of suspected cases through investigating the epidemiological and clinical manifestations of confirmed cases of new-type coronavirus infection in children. Methods We retrospective analyzed the epidemiological and clinical manifestations of 6 children with new coronavirus infection diagnosed in Chongqing Three Gorges Central Hospital from February 3, 2020 to February 15, 2020 . Compared with the diagnostic criteria of suspected cases,we summarized the problems encountered in the application of this standard in clinical work and try to put forward Suggestions for improvement. Results Among the 6 children with confirmed cases: 5 males and 1 female; 3 from Hubei Province and 3 from Wanzhou ; 6 cases of clustered onset of the family; Visiting nature: 3 cases of suspected case income, 3 cases of community or outpatient screening . Three cases with fever and / or respiratory symptoms, one of which had symptoms of diarrhea; all children's blood routine and lymphocyte counts were within the normal range; chest CT imaging except for cases No. 1 and No. 5 were in line with typical new coronavirus pneumonia signs. In addition, the remaining 3 patients had abnormal imaging but did not have the characteristics of new coronavirus pneumonia, and 1 case was normal. Comparison results:Only case 1 of all cases fully met the diagnostic criteria, and the remaining cases did not meet the diagnostic criteria of early suspected cases. Conclusion In order to improve the accuracy and practicality of the diagnosis of suspected cases in children, it is recommended to refine and standardize the diagnostic criteria of some suspected cases.",2020,"JIANG, Jianyu; DUAN, Ling; XIONG, Daoxue; FENG, Yan; LIU, Xiangjun; YU, Jie; PENG, Zhe; LANG, Chunhui",Chinese Pediatric Emergency Medicine,1981966501,#2238,
,CZI,Experience of treating severe cases of 2019 novel coronavirus pneumonia in Changde area,10.1097/JCMA.0000000000000270,,,,"Since the cluster of the 2019 novel coronavirus (2019-nCoV) pneumonia, a large number of patients gathered, the mortality of critical patients has remained high and the treatment was unclear. In this outbreak, Hunan Changde region immediately set up a hospital and intensive care unit. The patients relieved through respiratory support, hemodynamics management, nutritional support, the application of antiviral drugs, analgesic and sedation. The treatment experience in severe cases of 2019-nCov pneumonia patients were summarized as follows: in terms of respiratory support, we needed to pay attention to the advantages of high-flow nasal cannula oxygen therapy (HFNC) and the intervention of mechanical ventilation, pay attention to the ventilator parameters, and adopt prone position timely. In the aspects of fluid resuscitation and volume management, we should pay attention to the characteristics of severe patients' volume status, perform early evaluation, and clinicians should focused on hemodynamic management beside the bed. In the aspect of nutritional support and evaluation and maintenance of intestinal function, early enteral nutrition should be adopted in time. However, the trade-off between the risk of intestinal function and nutritional support in patients with mechanical ventilation and the antiviral benefits of Kaletra needed to be reevaluated, the optimized way of analgesia and sedation was adopted, at the same time, the usage and side effects of antiviral drugs should be paid attention to. We should grasp the opportunity of transportation for severe patients. It is suggested that some warning scores should be used to facilitate early recognition of patients with severe infection and then they should be earlier transferred to the designated hospital for intensive care.",2020,"JIN, Xin; FANG, Yimin; HUANG, Shaohua; LUO, Lin; QIN, Yunjian; ZHOU, Rui; PENG, Yue; YANG, Mingshi; AI, Yuhang",Chinese Critical Care Medicine,3006472059,#2235,
,CZI,The explosive epidemic outbreak of novel coronavirus disease 2019 (COVID-19) and the persistent threat of respiratory tract infectious diseases to global health security,10.1097/mcp.0000000000000676,,32132379,,,2020,"Zumla, A.; Niederman, M. S.",Current opinion in pulmonary medicine,3006645647,#5544,
,CZI,Materialism and dialectics of epidemic prevention and control: only by respecting science can we get twice the result with half the effort,10.1097/PHH.0000000000000326,,,,"The epidemic caused by 2019 novel coronavirus has been highly concerned by the international community including World Health Organization (WHO). This is an endless battle against human life and health. Never forget the past, the teacher of the future. When you think hard, draw inferences from one instance. Many phenomena and problems in the work of epidemic prevention, control and treatment are worthy of our deep reflection. We should use scientific thinking and dialectical materialism to make a practical and realistic summary. The purpose is to win the battle as soon as possible, and more importantly, to avoid repeating the same mistakes and prevent trouble before it happens.",2020,"WU, Xiukun",Chinese Critical Care Medicine,2341369673,#2119,
,CZI,Chest CT Findings in Patients with Corona Virus Disease 2019 and its Relationship with Clinical Features,10.1097/RLI.0000000000000670,,32091414,,"OBJECTIVES: To investigate the chest computed tomography (CT) findings in patients with confirmed corona virus disease 2019 (COVID-19) and to evaluate its relationship with clinical features. MATERIALS AND METHODS: Study sample consisted of 80 patients diagnosed as COVID-19 from January to February 2020. The chest CT images and clinical data were reviewed and the relationship between them was analyzed. RESULTS: Totally 80 patients diagnosed with COVID-19 were included. With regards to the clinical manifestations, 58/80 (73%) of patients had cough, 61/80 (76%) of patients had high temperature levels. The most frequent CT abnormalities observed were ground glass opacity (GGO) (73/80 cases, 91%), consolidation (50/80 cases, 63%) and interlobular septal thickening (47/80, 59%). Most of the lesions were multiple, with an average of 12±6 lung segments involved. The most common involved lung segments were the dorsal segment of the right lower lobe (69/80, 86%), the posterior basal segment of the right lower lobe (68/80, 85%), the lateral basal segment of the right lower lobe (64/80, 80%), the dorsal segment of the left lower lobe (61/80, 76%) and the posterior basal segment of the left lower lobe (65/80, 81%). The average pulmonary inflammation index (PII) value was (34%±20%) for all the patients. Correlation analysis showed that the PII value was significantly correlated with the values of lymphocyte count, monocyte count, C-reactive protein, procalcitonin, days from illness onset and body temperature (p<0.05). CONCLUSION: The common chest CT findings of COVID-19 are multiple GGO, consolidation and interlobular septal thickening in both lungs, which are mostly distributed under the pleura. There are significant correlations between the degree of pulmonary inflammation and the main clinical symptoms and laboratory results. CT plays an important role in the diagnosis and evaluation of this emerging global health emergency.",2020,"Wu, Jiong; Wu, Xiaojia; Zeng, Wenbing; Guo, Dajing; Fang, Zheng; Chen, Linli; Huang, Huizhe; Li, Chuanming",Invest Radiol,2824769728,#1744,
,CZI,The Clinical and Chest CT Features Associated with Severe and Critical COVID-19 Pneumonia,10.1097/RLI.0000000000000672,,32118615,,"OBJECTIVE: To investigate the clinical and CT features associated with severe and critical Corona Virus Disease 2019 (COVID-19) pneumonia. MATERIALS AND METHODS: Eighty-three patients with COVID-19 pneumonia including 25 severe/critical cases and 58 ordinary cases were enrolled. The chest CT images and clinical data of them were reviewed and compared. The risk factors associated with disease severity were analyzed. RESULTS: Compared with the ordinary patients, the severe/critical patients had older ages, higher incidence of comorbidities, cough, expectoration, chest pain and dyspnea. The incidences of consolidation, linear opacities, crazy-paving pattern and bronchial wall thickening in severe/critical patients were significantly higher than those of the ordinary patients. Besides, severe/critical patients showed higher incidences of lymph node enlargement, pericardial effusion and pleural effusion than the ordinary patients. The CT scores of severe/critical patients were significantly higher than those of the ordinary patients (P < 0.001). Receiver operating characteristic (ROC) curve showed that the sensitivity and specificity of CT Score were 80.0% and 82.8% respectively for the discrimination of the two types. The clinical factors of age > 50 years old, comorbidities, dyspnea, chest pain, cough, expectoration, decreased lymphocytes and increased inflammation indicators were risk factors for severe/critical COVID-19 pneumonia. CT findings of consolidation, linear opacities, crazy-paving pattern, bronchial wall thickening, high CT scores and extrapulmonary lesions were features of severe/critical COVID-19 pneumonia. CONCLUSIONS: There are significant differences in clinical symptoms, laboratory examinations and CT manifestations between the ordinary patients and the severe/critical patients. Many factors are related to the severity of the disease, which can help clinicians to judge the severity of the patient and evaluate the prognosis.",2020,"Li, Kunhua; Wu, Jiong; Wu, Faqi; Guo, Dajing; Chen, Linli; Fang, Zheng; Li, Chuanming",Invest Radiol,2145981491,#3060,
,CZI,Clinical and High-Resolution CT Features of the COVID-19 Infection: Comparison of the Initial and Follow-up Changes,10.1097/rli.0000000000000674,,32134800,,"OBJECTIVES: In late December, 2019, an outbreak of coronavirus disease (COVID-19) in Wuhan, China was caused by a novel coronavirus, newly named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to quantify severity of COVID-19 infection on High-Resolution CT and to determine its relationship with clinical parameters. MATERIALS AND METHODS: From Jan 11, 2020, to Feb 5, 2020, the clinical, laboratory and HRCT features of 42 patients (26-75 years, 25 males) with COVID-19 were analyzed. The initial and follow-up CT obtained a mean of 4.5 days and 11.6 days from the illness onset were retrospectively assessed for the severity and progression of pneumonia. Correlations among clinical parameters, initial CT features and progression of opacifications were evaluated with Spearman correlation and linear regression analysis. RESULTS: Thirty-five (83%) patients exhibited a progressive process according to CT features during the early stage from onset. Follow-up CT findings showed progressive opacifications, consolidation, interstitial thickening, fibrous strips and air bronchograms, compared to initial CT (all p<0.05). Before regular treatments, there was a moderate correlation between the days from onset and sum score of opacifications (R=0.68, p<0.01). The C-reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase showed significantly positive correlation with the severity of pneumonia assessed on initial CT (R range 0.36-0.75, p<0.05). The highest temperature and the severity of opacifications assessed on initial CT were significantly related to the progression of opacifications on follow-up CT (p=0.001-0.04). CONCLUSIONS: Patients with the COVID-19 infection usually presented with typical ground-grass opacities and other CT features, which showed significant correlations with some clinical and laboratory measurements. Follow-up CT images often demonstrated progressions during the early stage from illness onset.",2020,"Xiong, Y.; Sun, D.; Liu, Y.; Fan, Y.; Zhao, L.; Li, X.; Zhu, W.",Investigative radiology,2014210218,#5341,
,CZI,Management highlights for patients with orthopedic trauma during the epidemic of Corona Virus Disease 2019,10.1097/TA.0000000000002292,,,,"Although the epidemic outbreak of Corona Virus Disease 2019 (COVID-19) restricted freecoming and going of people, it was inevitable that fracture patients, elderly ones with low-energy fracture in part ICU lar, sought medical attention. In this special situation, itwas crucial for trauma orthopaedists to do well in prevention and control of COVID-19 infection and in perioperative management of their patients as well while they went on with routine diagnosis and treatment. It was also of great significance for prognosis of the patients and prevention and control of the epidemic that orthopaedic surgeons chose proper surgical and anesthesia methods. In the process of diagnosis, treatment, nursing and rehabilitation, medical staff too was challenged by how to prevent themselves from infection and how to eliminate cluster COVID-19 transmission. This paper, from the perspectives of orthopedic surgeons, nurses and patients, expounds briefly on the management of patients with orthopedic trauma during the epidemic period of COVID-19 in a mode of multidisciplinary comprehensive interventions.",2020,"YIN, Yingchao; HOU, Zhiyong; ZHU, Yanbin; YANG, Shuhong; CHEN, Wei; WANG, Xiuli; LI, Xiuting; ZHANG, Qi; ZHANG, Yingze",Chinese Journal of Orthopaedic Trauma,2928212465,#2080,
,CZI,Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients,10.1099/0022-1317-81-11-2755,,,,"Background: A patient’s infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. Methods: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients’ oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. Results: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0–62.0) years were analyzed. After in-hospital treatment, patients’ inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0–11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients’ stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0–16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0–4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients’ urine specimens after throat swabs were negative. Using a multiple linear regression model ( F =2.669, P =0.044, and adjusted R 2 =0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients’ stools ( t =-2.699, P =0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs 8.0 days, respectively; t =2.550, P =0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs 11 days, respectively; t =4.631, P <0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results ( P >0.05). Conclusions: In brief, as the clearance of viral RNA in patients’ stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.",2020,"LING, Yun; XU, Shui Bao; LIN, Yi Xiao; TIAN, Di; ZHU, Zhao Qin; DAI, Fa Hui; WU, Fan; SONG, Zhi gang; HUANG, Wei; CHEN, Jun; HU, Bi Jie; WANG, Sheng; MAO, En Qiang; ZHU, Lei; ZHANG, Wen Hong; LU, Hong Zhou",Chinese Medical Journal,2157458496,#2192,
,CZI,"Clinical analysis of 23 cases of 2019 novel coronavirus infection in Xinyang City, Henan Province",10.1101/2020.02.06.20020974,,,,"Objective To analyze the epidemiological characteristics and clinical features of the patients with 2019-nCoV infection, so as to provide basis for clinical diagnosis. Methods The epidemiology, clinical symptoms, laboratory and radiologic data of 23 patients with 2019-nCoV infection admitted to the Fifth People's Hospital of Xinyang City from January 22,2020 to January 29, 2020 were retrospectively analyzed. Results The 23 patients with 2019 nCov infection consisted of 15 men and 8 women, and the median age was 46.0 (40.5, 52.0) years (27-80 years); 9 of them had basic disease (39%), including hypertension (17%), cardiovascular diseases (17%), diabetes (9%), hypothyroidism (4%) and old tuberculosis (4%). All the 23 patients had contact history in Wuhan area or with confirmed infections. Clinical symptoms included: fever (100%), cough (70%), expectoration (43%), myalgia (26%), headache (17%) and dyspnea (17%), and the less common symptoms were diarrhea (4.3%). Blood routine test: white blood cells (WBC) < 4×10 9 /L in 11 cases (48%), (4-10)×10 9 /L in 10 cases (43%), >10 × 109/L in 2 cases (9%); lymphocytopenia in 13 cases (56%). All 23 patients had different degrees of infective lesions in chest CT examination, with 9 cases (39%) on one side and 14 cases (61%) on both sides. Classification: 19 mild cases, 4 severe cases, no critical or death case. Complications included acute respiratory distress syndrome [4 (17%)]. No case was reported with the damage of liver or kidney function and with secondary infection. Conclusions Epidemic history of contact, fever, pneumonia signs of chest CT, normal or decreased count of WBC and lymphocytopenia are the clinical basis for diagnosis of the disease. However, at present, the treatment of patients has not been completed, the effective treatment strategy and final prognosis are not clear.",2020,"XU, Ming; LI, Mengdie; ZHAN, Weiqiang; HAN, Tao; LIU, Litao; ZHANG, Guosheng; LU, Yibin",Chinese Critical Care Medicine,3005477624,#2101,
,CZI,Reconsideration on the multiple value of Behavior determining Health: in the perspective of the situation of COVID-19,10.1109/MPUL.2014.2355302,,,,"Why has the concept of behavior determining health created more and more extensive and far-reaching influence ever since it was put forward? The reason lies in its multiple values. It is of great practical significance and has important implications for long-term health care to explore and analyze in the perspective of the situation of COVID-19 its philosophical values, cultural values, methodological values, social values and the national strategic value of 'healthy China'.",2020,"ZHU, Lifang; BIE, Mingke; SONG, Guojian; YANG, Zhiyin",Chinese Journal of Behavioral Medicine and Brain Science,1979830743,#2041,
,CZI,"Gold nanoparticle‐adjuvanted S protein induces a strong antigen‐specific IgG response against severe acute respiratory syndrome‐related coronavirus infection, but fails to induce protective antibodies and limit eosinophilic infiltration in lungs",10.1111/1348-0421.12754,,,,"The spike (S) protein of coronavirus, which binds to cellular receptors and mediates membrane fusion for cell entry, is a candidate vaccine target for blocking coronavirus infection. However, some animal studies have suggested that inadequate immunization against severe acute respiratory syndrome coronavirus (SARS‐CoV) induces a lung eosinophilic immunopathology upon infection. The present study evaluated two kinds of vaccine adjuvants for use with recombinant S protein: gold nanoparticles (AuNPs), which are expected to function as both an antigen carrier and an adjuvant in immunization; and Toll‐like receptor (TLR) agonists, which have previously been shown to be an effective adjuvant in an ultraviolet‐inactivated SARS‐CoV vaccine. All the mice immunized with more than 0.5 µg S protein without adjuvant escaped from SARS after infection with mouse‐adapted SARS‐CoV; however, eosinophilic infiltrations were observed in the lungs of almost all the immunized mice. The AuNP‐adjuvanted protein induced a strong IgG response but failed to improve vaccine efficacy or to reduce eosinophilic infiltration because of highly allergic inflammatory responses. Whereas similar virus titers were observed in the control animals and the animals immunized with S protein with or without AuNPs, Type 1 interferon and pro‐inflammatory responses were moderate in the mice treated with S protein with and without AuNPs. On the other hand, the TLR agonist‐adjuvanted vaccine induced highly protective antibodies without eosinophilic infiltrations, as well as Th1/17 cytokine responses. The findings of this study will support the development of vaccines against severe pneumonia‐associated coronaviruses.",2020,"Sekimukai, Hanako; Iwata; Yoshikawa, Naoko; Fukushi, Shuetsu; Tani, Hideki; Kataoka, Michiyo; Suzuki, Tadaki; Hasegawa, Hideki; Niikura, Kenichi; Arai, Katsuhiko; Nagata, Noriyo",Microbiology and Immunology,2982765016,#70,
,CZI,World Economic Prospects Monthly,10.1111/1468-0319.12472,,,,"Overview: Coronavirus to cut global growth to new lows ▀ The rapid spread of coronavirus will weaken China's GDP growth sharply in the short term, causing disruption for the rest of the world. We now expect global GDP growth to slow to just 1.9% y/y in Q1 this year and have lowered our forecast for 2020 as a whole from 2.5% to 2.3%, down from 2.6% in 2019. ▀ Prior to the coronavirus outbreak, there had been signs that the worst was over for both world trade and the manufacturing sector. However, this tentative optimism has been dashed by the current disruption. ▀ While the near-term impact of the virus is uncertain, the disruption to China will clearly be significant in Q1 ? we expect Chinese GDP growth to plunge to just 3.8% y/y. Even though growth there will rebound in Q2 and Q3, it will take time for the loss in activity to be fully recovered and we now expect GDP growth of just 5.4% for 2020 as a whole, a downward revision of 0.6pp from last month. ▀ Weaker Chinese imports and tourism and disruption to global supply chains will take a toll on the rest of the world, particularly in the Asia-Pacific region. And the shock will exacerbate the ongoing slowdown in the US and may result in the eurozone barely expanding for a second quarter running in Q1. ▀ Weaker oil demand in the short term has prompted us to lower our Brent oil price forecast. We have cut our projection for growth in crude demand in 2020 by 0.2m b/d to 0.9 mb/d and now forecast Brent crude will average $62.4pb in 2020, down from about $65pb in our January forecast. ▀ Quarterly global growth is likely to strengthen a little in H2 this year as the disruption fades and firms make up for the lost output earlier in the year and the effect of China's policy response starts to feed through. But for 2020 overall, global growth is now likely to be just 2.3%, 0.2pp weaker than previously assumed as a result of the epidemic.",2020,,Economic Outlook,39126301,#1711,
,CZI,From the frontlines of COVID-19 – How prepared are we as obstetricians: a commentary,10.1111/1471-0528.16192,,,,"Abstract The World Health Organization (WHO) has declared the outbreak of novel coronavirus (2019-nCoV) ? now known as Coronavirus Disease (COVID-19)1 - as a global health emergency. Singapore currently stands as the country with the highest number of reported cases of COVID-19 outside of China2, excluding patients on a cruise ship offshore of Japan.",2020,"Chua, Monica Shi Qi; Lee, Jill Cheng Sim; Sulaiman, Suzanna; Tan, Hak Koon",BJOG: An International Journal of Obstetrics & Gynaecology,,#4027,
,CZI,2019 novel coronavirus infection and gastrointestinal tract,10.1111/1751-2980.12851,,32096611,,"Since end of December 2019, a cluster of patients with pneumonia of unknown origin was reported from Wuhan, Hubei province, China. As of Feb 17th, 2020, statistical data show that the outbreak constitutes an epidemic threat in China, where the exponential increase in patients has reached 75114 confirmed cases, with 2239 deaths. Different from SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus) infection, the initial presentations or the chief complain of some patients with the 2019 novel coronavirus (COVID-19) were gastrointestinal symptoms. So we call upon all the first-line medical staff to be cautious and pay more attention to those untypical patients especially from the epidemic area. Besides, as the viral nucleic acids could be found in the fecal samples and anal swabs of some patients with COVID-19 infection, the possibility of fecal-oral transmission need to be took into account. Based on the previously and recently studies, we speculate that COVID-19 may have some relationship with the gut microbiota through angiotensin-converting enzyme 2 (ACE2) receptor, thus targeting gut microbiota might be a new therapeutic option for the treatment of virus-related pneumonia. This article is protected by copyright. All rights reserved.",2020,"Gao, Qin Yan; Chen, Ying Xuan; Fang, Jing Yuan",J Dig Dis,3004896587,#1991,
,CZI,The Novel Coronavirus – A Snapshot of Current Knowledge,10.1111/1751-7915.13557,,,,"Summary Another animal to human transmission of a coronavirus occurred in December 2019 on a live animal market in the Chinese city of Wuhan causing an epidemic in China, reaching now different continents. This minireview summarizes the research literature on the virological, clinical and epidemiological aspects of this epidemic published until end of February 2020.",2020,"Brüssow, Harald",Microbial Biotechnology,,#5073,
,CZI,Hospital Emergency Management Plan During the COVID-19 Epidemic,10.1111/acem.13951,,,,"Abstract The confirmed and suspected cases of the 2019 novel coronavirus disease (COVID-19) have increased not only in Wuhan, Hubei Province but also China and the world. Enormous demand for handling the COVID-19 outbreak challenged both the healthcare personnel and medical supply system. In West China Hospital, Emergency Department (ED) undertook the mission of clinical reception, primary diagnosis, and interim treatment for the suspected cases of COVID-19.",2020,"Cao, Yubin; Li, Qin; Chen, Jing; Guo, Xia; Miao, Cheng; Yang, Hui; Chen, Zihang; Li, Chunjie",Academic Emergency Medicine,2322715620,#3204,
,CZI,Editorial 58(1),10.1111/aje.12732,,,,"As I write, the world is gripped by news of a novel coronavirus sweeping across the planet. The epidemic is causing terrible anguish to many thousands of families and astounding economic damage in Asia. Whilst yet unconfirmed, several research results now point at the hunting, trade and consumption of pangolins as a likely source of the epidemic. Whether or not pangolins do finally prove to be at the origin of this particular virus, the research highlights that the possibility is very real. This may turn out to be a turning point for pangolin conservation, perhaps for the conservation of a great many other species. In 2015, the IUCN Species Survival Commission Pangolin Specialist Group reported concerns that the profound decline in Asian pangolins would lead to traffickers procuring supplies from Africa. The next five years saw their predictions largely fulfilled. Robust results from a range of research approaches showed first an increase in trade and value of pangolins within the West and central Africa and, more recently, growing international trafficking, with China and Vietnam as major destinations. In 2016, the CITES 17th Conference of Parties moved all African pangolin species onto Appendix 1. Not a single research paper published on pangolins in the past 5 years has suggested anything other than desperate jeopardy for all eight of the world’s species. All available researches point to increasing harvesting, with the rise ultimately driven by trade for profit. The plight of over‐hunted pangolins has become a rallying call for conservation over the past few years. New NGO and government funding initiatives have arisen, dedicated to research for their conservation. The dramatically steep decline of the Asian species has been written about in both Science and Nature, the most widely read scientific journals of the day, in the last few years. The pangolin, alongside the elephant, is a poster species for action against the illegal wildlife trade. However, the research community’s awareness of the impending doom has not in the least stemmed the trade. This issue contains a Short Communication reporting for the first time trade in pangolins in yet another country, South Sudan. I am unsure of what the public response to the possibility that pangolins can transmit deadly viruses will be. I hope it is to leave them alone, rather than to try to eradicate them. This Journal remains committed to improving knowledge of the African ecosystems and increasingly to reporting research that shows how they are changing in the face of our actions. This issue, as each issue, makes a new and relevant contribution to that objective.",2020,"Abernethy, Katharine",African Journal of Ecology,3000618339,#3469,
,CZI,"Initial public health response and interim clinical guidance for the 2019 novel coronavirus outbreak - United States, December 31, 2019-February 4, 2020",10.1111/ajt.15805,,32090470,,,2020,"Patel, Anita; Jernigan, Daniel B.; nCo, V. C. D. C. Response Team",Am J Transplant,3004775012,#454,
,CZI,Coronavirus Disease 2019: Implications of Emerging Infections for Transplantation,10.1111/ajt.15832,,32090448,,"The recent identification of an outbreak of 2019- novel Coronavirus is currently evolving, and the impact on transplantation is unknown. However, it is imperative that we anticipate the potential impact on the transplant community in order to avert severe consequences of this infection on both the transplant community and contacts of transplant patients.",2020,"Michaels, Marian G.; La Hoz, Ricardo M.; Danziger Isakov, Lara; Blumberg, Emily A.; Kumar, Deepali; Green, Michael; Pruett, Timothy L.; Wolfe, Cameron R.",Am J Transplant,2896660745,#1800,
,CZI,"Clinical characteristics of 140 patients infected by SARS-CoV-2 in Wuhan, China",10.1111/all.14238,,32077115,,"BACKGROUND: Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) infection has been widely spread. We aim to investigate the clinical characteristic and allergy status of patients infected by SARS-CoV-2. METHODS: Electronical medical records including demographics, clinical manifestation, comorbidities, laboratory data and radiological materials of 140 hospitalized COVID-19 patients, with confirmed result of SARS-CoV-2 viral infection were extracted and analysed. RESULTS: An approximately 1:1 ratio of male (50.7%) and female COVID-19 patients was found, with an overall median age of 57.0 years. All patients were community acquired cases. Fever (91.7%), cough (75.0%), fatigue (75.0%) and gastrointestinal symptoms (39.6%) were the most common clinical manifestations, whereas hypertension (30.0%) and diabetes mellitus (12.1%) were the most common comorbidities. Drug hypersensitivity (11.4%) and urticaria (1.4%) were self-reported by several patients. Asthma or other allergic diseases was not reported by any of the patients. Chronic obstructive pulmonary disease (COPD, 1.4%) and current smokers (1.4%) were rare. Bilateral ground glass or patchy opacity (89.6%) were the most common signs of radiological finding. Lymphopenia (75.4%) and eosinopenia (52.9%) were observed in most patients. Blood eosinophil counts correlate positively with lymphocyte counts in severe (r=0.486, p<0.001) and non-severe (r=0.469, p<0.001) patients after hospital admission. Significantly higher levels of D-dimer, C-reactive protein and procalcitonin were associated with severe patients compared to non-severe patients (all p<0.001). CONCLUSION: Detailed clinical investigation of 140 hospitalized COVID-19 cases suggest eosinopenia together with lymphopenia may be a potential indicator for diagnosis. Allergic diseases, asthma and COPD are not risk factors for SARS-CoV-2 infection. Elder age, high number of comorbidities and more prominent laboratory abnormalities were associated with severe patients.",2020,"Zhang, Jin-Jin; Dong, Xiang; Cao, Yi-Yuan; Yuan, Ya-Dong; Yang, Yi-Bin; Yan, You-Qin; Akdis, Cezmi A.; Gao, Ya-Dong",Allergy,3005079553,#1433,
,CZI,Novel corona virus disease (COVID-19) in pregnancy: What clinical recommendations to follow?,10.1111/aogs.13836,,,,"Interim guidance has been issued by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) on managing COVID-19, which include some recommendations specific to pregnant women mostly drawn on experience from previous coronavirus outbreaks.8, 9 Chinese expert recommendations for the care of pregnant women with suspected and confirmed COVID-9 were developed and disseminated in China quite early following the outbreak in Wuhan.10 These recommendations have been dynamic, evolving as more knowledge about epidemiology, pathogenesis, disease progression and clinical course among infected pregnant patients has been gathered. Limited clinical experience in managing pregnant women with COVID-19 and their neonates has been reported from China recently based on a case series of nine pregnancies with confirmed COVID-19 treated in Zhongnan Hospital of Wuhan University and 10 neonates (nine pregnancies) delivered at five different hospitals,11, 12 although many more cases (>100) of suspected or confirmed COVID-19 have been treated and delivered in several hospitals in China according to the news releases and media reports. So far, no maternal deaths have been reported. There appears to be some risk of premature rupture of membranes, preterm delivery, fetal tachycardia and fetal distress when the infection occurs in the third trimester of pregnancy. However, there is no evidence suggesting transplacental transmission based on very limited data, as the analysis of amniotic fluid, cord blood, neonatal throat swab, and breast milk samples available from six of the nine patients were found to be negative for SARS-COV-2. Whether virus shedding occurs vaginally is also not known.",2020,"Liang, Huan; Acharya, Ganesh",Acta Obstetricia et Gynecologica Scandinavica,3006645647,#4514,
,CZI,Emergency management for preventing and controlling nosocomial infection of 2019 novel coronavirus: implications for the dermatology department,10.1111/bjd.19011,,,,"Summary As of Feb 15, 2019, the novel coronavirus (2019-nCoV) has rapidly spread throughout China and across the world with more than 60,000 laboratory-confirmed cases. Due to the current lack of specific treatment and the risk of transmission during the viral incubation period, infection prevention and control of 2019-nCoV are both urgent and critical to global health. In this article, we aim to highlight the necessity of implementing protective measures, and recommend how to set proper emergency management plans for preventing and controlling nosocomial infection of 2019-nCoV in dermatology departments.",2020,"Tao, J.; Song, Z.; Yang, L.; Huang, C.; Feng, A.; Man, X.",British Journal of Dermatology,2356688126,#4435,
,CZI,The novel Chinese coronavirus (2019-nCoV) infections,10.1111/eci.13135,,,,,2020,,European Journal of Clinical Investigation,3004412595,#2706,
,CZI,The Novel Chinese Coronavirus (2019-nCoV) Infections: challenges for fighting the storm,10.1111/eci.13209,,32003000,,"Since end of December 2019, a cluster of patients with pneumonia of unknown origin was reported from Wuhan, Hubei province, China. They shared a connection with the Huanan South China Seafood Market in Wuhan, and now it has been confirmed that the disease is caused by a novel coronavirus (provisionally named 2019-nCoV). As of today (30 January 2020), 7734 cases have been confirmed in China, and 90 cases have also been cumulatively reported from Taiwan, Thailand, Vietnam, Malaysia, Nepal, Sri Lanka, Cambodia, Japan, Singapore, Republic of Korea, United Arab Emirate, United States, The Philippines, India, Australia, Canada, Finland, France, and Germany (Finland, France and Germany are the only European countries in which cases [n= 1, n = 5, and n = 4, respectively] have been reported up to date). According to the released news, the case rate fatality is 2.2% (170/7824).",2020,"Bassetti, M.; Vena, A.; Roberto Giacobbe, D.",European journal of clinical investigation,3004412595,#113,
,CZI,"A combination regimen by lopinave/litonawe (LPV/r), emtricitabine and tenofovir alafenamide fumarate (FTC/TAF) for treatment of novel coronavirus pneumonia (TARCoV)",10.1111/hiv.12833,,,,"Objective To explore the efficacy of a combination regimen by Lopinave/Litonawe (LPV/r), emtricitabine and tenofovir alafenamide fumarate (FTC/TAF) for the treatment of novel coronavirus pneumonia (NCP). Methods We design the protocol as a real world study, which includes two groups: prospective intervention cohort (T1) and historical control group (T2). For T1 group, ninety patients will be enrolled who are diagnosed as NCP. All patients in T1 group will receive standard therapies following the recommendation in the guidelines of National Commission of Health, and they will be administered an anti-virus regimen includes LPV/r and FTC/TAF. The T2 group will enroll patients who have received single regimen includes LPV/r. The major outcome is the survival rate of patients. Secondary outcomes are the time of seroconversion of RNA, ARDS progression rate and length of hospital stay. Conclusions The results of this real world study might provide clinical practitioners a high efficiency and fast antivirus regimen for NCP. In addition, the conduction of this study will accelerate screening for other new effective therapeutic method.",2020,"JIANG, Hua; WANG, Yu; WANG, Kai; YANG, Xingxiang; ZHANG, Jiancheng; DENG, Hongfei; WANG, Lu; ZENG, Jun",Chinese Journal of Emergency Medicine,3005182192,#2239,
,CZI,The world is changing fast!,10.1111/ijcp.13486,,,,"The world is changing fast! As of 9 February 2020, there now have been at least 813 deaths from a novel strain of coronavirus that is thought to have originated in Wuhan, China (2019-nCoV), at the end of 2019. These deaths are in the context of the 37 558 cases of 2019-nCov which have already been diagnosed in China and multiple other countries.1 In the United Kingdom (UK), recent research by University College London, funded by the Nuffield Foundation, has found that 1 in 20 UK teachers now report long-lasting mental health problems, illustrating a dramatic increase from around 1/100 teachers affected in this way in the 1990s.2 In the United States (US), a recent report by Accenture (Artificial Intelligence [AI]: Healthcare's new nervous system), estimates that AI in health will be worth around $6.6 billion by 2021 and that “…when combined, key clinical health AI applications can potentially create $150 billion in annual savings for the US healthcare economy by 2026.”3 What do these facts and statistics have in common? Taken together they illustrate the massive range and rate of change in health and the responsibility of healthcare globally. In this context a valid question can be asked about the role of general medical journals such as the International Journal of Clinical Practice (IJCP). Having taken over as Editor in Chief of IJCP in January this year, I have the honour of leading an internationally renowned medical journal, with a team of extremely accomplished clinician editors, published by Wiley, one of the world's leading biomedical publishers. In our rapidly changing healthcare world, IJCP is eager, committed and ideally suited to undergo a transition process as well. As a team, our view is that in a healthcare environment of seemingly ever-increasing specialisation, one key role that a Journal such as ours should move to fulfil is to publish important, high quality medical research and opinion that will inform specialist clinicians about important general medical concepts, practical insights and recent advances. Similarly, we will also aim to inform generalists about key speciality medical advances that have relevance to generalists in the provision of care to their patients. In this work a foundational aspect of our editorial approach will be rather than looking for reasons to reject submissions, to clearly identify problems with submitted research and opinion if they exist, and work closely with authors to address these issues, allowing those authors to raise the quality of their work to the highest level. In that context, as well as continuing to publish submissions from internationally important clinicians and medical researchers worldwide, we also see that IJCP should aim to specifically encourage less experienced authors who nonetheless have important information to share with the global healthcare community. In this way, IJCP will drive forward its primary function of improving global health through the dissemination of world leading medical information and debate. The world is changing fast, and IJCP has the energy and vision to change with it!",2020,"Young, Charles",International Journal of Clinical Practice,1600193582,#2076,
,CZI,"The 2019 Coronavirus: Learning Curves, Lessons, and the Weakest Link",10.1111/ijcp.13488,,32052918,,"In the space of just six weeks, a new coronavirus, from a family that historically was not viewed as a global health concern, has become daily headline news around the globe. The 21(st) century marked its arrival with the emergence of three previously unknown coronaviruses. SARS-CoV (severe acute respiratory syndrome coronavirus) was recognized in November 2002 [1, 2], MERS-CoV (Middle East respiratory syndrome coronavirus) in June 2012 [3, 4], and 2019-nCoV in December 2019 [5]. Previously, human coronaviruses, known since the 1960s, were viewed as being only marginally relevant to the clinic, except for infants, the elderly, and immunocompromised individuals [1, 6, 7].",2020,"Stein, Richard Albert",Int J Clin Pract,3006608759,#863,
,CZI,Global challenges in health and health care for nurses and midwives everywhere,10.1111/inr.12578,,32083728,,"The next decade is likely to produce any number of global challenges that will affect health and health care, including pan-national infections such as the new coronavirus COVID-19 and others that will be related to global warming. Nurses will be required to react to these events, even though they will also be affected as ordinary citizens. The future resilience of healthcare services will depend on having sufficient numbers of nurses who are adequately resourced to face the coming challenges.",2020,"Catton, H.",Int Nurs Rev,1998583863,#1682,
,CZI,Anesthesia management for cesarean section during novel coronavirous epidemic,10.1111/j.1447-0756.1995.tb00913.x,,,,"Thirty-six puerperas who underwent emergency cesarean section at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 24, 2020 to February 9, 2020, who all wore medical surgical masks, were retrospectively included in this study. Anesthesia management was performed under tertiary medical protection measures. A dedicated anesthesia equipment was separately sterilized. Narcotic drugs were used for one patient only, and disposable medical supplies were used for anesthetic supplies. Contact transmission should be avoided when a neonate required resuscitation, and early isolation and nucleic acid testing were provided for the neonates. The rate of suspected cases of novel coronavirus (2019-nCoV) was 11% , and the rate of clinically diagnosed cases was 17% before surgery. The rate of clinically diagnosed cases of 2019-nCoV was 22%, the rate of confirmed cases was 8%, and the total positive rate of diagnosis was 31% after surgery. The rate of neuraxial anesthesia was 86%, the rate of general anesthesia was 14%, the time of spinal puncture was (15±7) min, the time of tracheal intubation under general anesthesia was (2.1±1.3) min, the operation time was (95±36) min, and blood loss was (276±166) ml. The Apgar score of newborns was 8.8 ± 0.5. There was 1 neonate whose mother was diagnosed as having 2019 novel coronavirous disease after operation, an oropharyngeal swab specimen was obtained at 36 h of birth, and the swab was tested positive for 2019-nCoV by nucleic acid testing. As of February 10, 2020, an anesthesiologist involved in the operation was diagnosed to have infection by 2019-nCoV. In conclusion, diagnosis of 2019 novel coronavirous disease during pregnancy is more difficult, it is necessary to perform anesthesia management for cesarean section under tertiary medical protection. Although the difficulty in anesthesia operation is increased under tertiary medical protection, anesthesiologists can carry out standardized anesthesia management and guarantee the safety of maternal and infants and anesthesiologists themselves as long as they are rigorously trained and adhere to protective protocols.",2020,"ZHOU, Zhiqiang",Chinese Journal of Anesthesiology,2045416734,#2044,
,CZI,Novel coronavirus pneumonia related liver injury: etiological analysis and treatment strategy,10.1111/j.1478-3231.2006.01349.x,,,,"The outbreak of novel coronavirus pneumonia(NCP) caused by 2019 novel coronavirus has become a global public health challenge. Some patients accompany with liver function damage in addition to the main typical respiratory symptom. Here we analyzed the clinical features, susceptible population, potential causes and therapeutic strategies of NCP related liver injury.",2020,"HU, Lilin; WANG, Weijun; ZHU, Qingjing; YANG, Ling",Chinese Journal of Hepatology,2076942479,#2261,
,CZI,Virus Isolation from the First Patient with SARS-CoV-2 in Korea,10.1111/j.1708-8305.2007.00165.x,,,,Novel coronavirus (SARS-CoV-2) is found to cause a large outbreak started from Wuhan since December 2019 in China and SARS-CoV-2 infections have been reported with epidemiological linkage to China in 25 countries until now. We isolated SARS-CoV-2 from the oropharyngeal sample obtained from the patient with the first laboratory-confirmed SARS- CoV-2 infection in Korea. Cytopathic effects of SARS-CoV-2 in the Vero cell cultures were confluent 3 days after the first blind passage of the sample. Coronavirus was confirmed with spherical particle having a fringe reminiscent of crown on transmission electron microscopy.Phylogenetic analyses of whole genome sequences showed that it clustered with other SARS- CoV-2 reported from Wuhan.,2020,"Park, Wan Beom",Journal of Korean Medical Science,1989129786,#3884,
,CZI,Preliminary prediction of the basic reproduction number of the Wuhan novel coronavirus 2019-nCoV,10.1111/jebm.12376,,32048815,,"OBJECTIVES: To estimate the basic reproduction number of the Wuhan novel coronavirus (2019-nCoV). METHODS: Based on the susceptible-exposed-infected-removed (SEIR) compartment model and the assumption that the infectious cases with symptoms occurred before 26 January, 2020 are resulted from free propagation without intervention, we estimate the basic reproduction number of 2019-nCoV according to the reported confirmed cases and suspected cases, as well as the theoretical estimated number of infected cases by other research teams, together with some epidemiological determinants learned from the severe acute respiratory syndrome (SARS). RESULTS: The basic reproduction number fall between 2.8 and 3.3 by using the real-time reports on the number of 2019-nCoV-infected cases from People's Daily in China and fall between 3.2 and 3.9 on the basis of the predicted number of infected cases from international colleagues. CONCLUSIONS: The early transmission ability of 2019-nCoV is close to or slightly higher than SARS. It is a controllable disease with moderate to high transmissibility. Timely and effective control measures are needed to prevent the further transmissions.",2020,"Zhou, Tao; Liu, Quanhui; Yang, Zimo; Liao, Jingyi; Yang, Kexin; Bai, Wei; Lu, Xin; Zhang, Wei",J Evid Based Med,3006177842,#707,
,CZI,Abnormal Coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia,10.1111/jth.14768,,,,"Abstract Background In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases were a concern. Objectives To describe the coagulation feature of patients with NCP. Methods Conventional coagulation results and outcomes of consecutive 183 patients with confirmed NCP in Tongji hospital were retrospectively analysed. Results The overall mortality was 11.5%, the non-survivors revealed significantly higher D-dimer and fibrin degradation product (FDP) levels, longer prothrombin time and activated partial thromboplastin time compared to survivors on admission (P<0.05). 71.4% of non-survivors and 0.6% survivors met the criteria of disseminated intravascular coagulation during their hospital stay. Conclusions The present study shows that abnormal coagulation results, especially markedly elevated D-dimer and FDP are common in deaths with NCP.",,"Tang, Ning; Li, Dengju; Wang, Xiong; Sun, Ziyong",Journal of Thrombosis and Haemostasis,2010736881,#1269,
,CZI,Bat-borne viruses in Africa: a critical review,10.1111/jzo.12769,,,,"Abstract In Africa, bat-borne zoonoses emerged in the past few decades resulting in large outbreaks or just sporadic spillovers. In addition, hundreds of more viruses are described without any information on zoonotic potential. We discuss important characteristics of bats including bat biology, evolution, distribution and ecology that not only make them unique among most mammals but also contribute to their potential as viral reservoirs. The detection of a virus in bats does not imply that spillover will occur and several biological, ecological and anthropogenic factors play a role in such an event. We summarize and critically analyse the current knowledge on African bats as reservoirs for corona-, filo-, paramyxo- and lyssaviruses. We highlight that important information on epidemiology, bat biology and ecology is often not available to make informed decisions on zoonotic spillover potential. Even if knowledge gaps exist, it is still important to recognize the role of bats in zoonotic disease outbreaks and implement mitigation strategies to prevent exposure to infectious agents including working safely with bats. Equally important is the crucial role of bats in various ecosystem services. This necessitates a multidisciplinary One Health approach to close knowledge gaps and ensure the development of responsible mitigation strategies to not only minimize risk of infection but also ensure conservation of the species.",,"Markotter, W.; Coertse, J.; De Vries, L.; Geldenhuys, M.; Mortlock, M.",Journal of Zoology,1980794434,#1283,
,CZI,2019_nCoV/SARS-CoV-2: rapid classification of betacoronaviruses and identification of Traditional Chinese Medicine as potential origin of zoonotic coronaviruses,10.1111/lam.13285,,32060933,,"The current outbreak of a novel severe acute respiratory syndrome-like coronavirus, 2019_nCoV(now named SARS-CoV-2), illustrated difficulties in identifying a novel coronavirus and its natural host, as the coding sequences of various Betacoronavirus species can be highly diverse. By means of whole-genome sequence comparisons, we demonstrate that the noncoding flanks of the viral genome can be used to correctly separate the recognized four betacoronavirus subspecies. The conservation would be sufficient to define target sequences that could, in theory, classify novel virus species into their subspecies. Only 253 upstream noncoding sequences of Sarbecovirus are sufficient to identify genetic similarities between species of this subgenus. Furthermore, it was investigated which bat species have commercial value in China, and would thus likely be handled for trading purposes. A number of coronavirus genomes have been published that were obtained from such bat species. These bats are used in Traditional Chinese Medicine, and their handling poses a potential risk to cause zoonotic coronavirus epidemics. SIGNIFICANCE AND IMPACT OF THE STUDY: The noncoding upstream and downstream flanks of coronavirus genomes allow for rapid classification of novel Betacoronavirus species and correct identification of genetic relationships. Although bats are the likely natural host of 2019_nCoV, the exact bat species that serves as the natural host of the virus remains as yet unknown. Chinese bat species with commercial value were identified as natural reservoirs of coronaviruses and are used in Traditional Chinese Medicine. Since their trading provides a potential risk for spreading zoonoses, a change in these practices is highly recommended.",2020,"Wassenaar, T. M.; Zou, Y.",Letters in applied microbiology,3006608991,#4187,
,CZI,Public responses to the novel 2019 coronavirus (2019-nCoV) in Japan: mental health consequences and target populations,10.1111/pcn.12988,,,,,2020,"Shigemura, Jun; Ursano, Robert J.; Morganstein, Joshua C.; Kurosawa, Mie; Benedek, David M.",Psychiatry and Clinical Neurosciences,3004837187,#496,
,CZI,Trust is a key factor in the willingness of health professionals to work during the COVID-19 outbreak: Experience from the H1N1 pandemic in Japan 2009,10.1111/pcn.12995,,,,"On May 16, 2009, Kobe City Medical Center General Hospital admitted the first domestically infected patient in Japan. The number of patients who were suspected as having H1N1 influenza grew to 1687 within two weeks. On May 27, when the mayor of Kobe city declared the emergency had subsided. The World Health Organization (WHO) declared H1N1 influenza as a pandemic on June 11, 2009. Details of this are described elsewhere4,5 . I am a psychiatrist but also worked at an outpatient unit that screened for H1N1 was worried about being infected. However, the chief of my department led the way by personally consulting at the outpatient unit, which motivated me to join as well. My experience made me conduct a cross-sectional survey about the willingness and hesitation to work during the H1N1 pandemic with 3635 employees at three core hospitals in Kobe city between June and July, 20096 .",2020,"Imai, Hissei",Psychiatry and Clinical Neurosciences,976943392,#2623,
,CZI,"MERS, SARS and other coronaviruses as causes of pneumonia",10.1111/resp.13196,,29052924,,"Human coronaviruses (HCoVs) have been considered to be relatively harmless respiratory pathogens in the past. However, after the outbreak of the severe acute respiratory syndrome (SARS) and emergence of the Middle East respiratory syndrome (MERS), HCoVs have received worldwide attention as important pathogens in respiratory tract infection. This review focuses on the epidemiology, pathogenesis and clinical characteristics among SARS-coronaviruses (CoV), MERS-CoV and other HCoV infections.",2018,"Yin, Yudong; Wunderink, Richard G.",Respirology,2766931063,#1349,
,CZI,"Novel coronavirus 2019, an emerging public health emergency",10.1111/tbed.13509,,32077206,,,2020,"Ward, Michael P.; Li, Xiangdong; Tian, Kegong",Transbound Emerg Dis,3003739945,#1468,
,CZI,The ongoing crises in China illustrate that the assessment of epidemics in isolation is no longer sufficient,10.1111/tbed.13536,,,,"Summary The interplay of simultaneous COVID-19, African swine fever, and avian influenza emergencies on global health and industries is constantly evolving and difficult to predict, and therefore warrants further scrutiny. The need for a health network of global scope for the rapid and open exchange of information needs to be strengthened in order to address ongoing and future epidemics under competing resources.",2020,"Stoffel, Carla; Schuppers, Manon; Buholzer, Patrik; Muñoz, Violeta; Lechner, Isabel; Sperling, Ulrich; Küker, Susanne; De Nardi, Marco",Transboundary and Emerging Diseases,2795682635,#5243,
,CZI,Tropical Medicine & International Health March 2020,10.1111/tmi.13254,,,,"Editorial An editorial on the COVID-19 epidemic summarizes the current knowledge about the disease and the novel SARS-CoV-2 virus. In particular, characteristics of the virus and treatment options are addressed",2020,,Tropical Medicine & International Health,3000969263,#3228,
,CZI,The Covid-19 epidemic,10.1111/tmi.13383,,,,"Abstract The current outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; previously 2019-nCoV), epi-centered in Hubei Province of the People's Republic of China, has spread to many other countries. On January 30, 2020, the WHO Emergency Committee declared a global health emergency based on growing case notification rates at Chinese and international locations. The case detection rate is changing hourly and daily and can be tracked in almost real time on website provided by Johns Hopkins University [1] and other websites. As of early February 2020, China bears the large burden of morbidity and mortality, whereas the incidence in other Asian countries, in Europe and North America remains low so far.",2020,"Velavan, Thirumalaisamy P.; Meyer, Christian G.",Tropical Medicine & International Health,3006419170,#722,
,CZI,"Inactivation of three emerging viruses - severe acute respiratory syndrome coronavirus, Crimean-Congo haemorrhagic fever virus and Nipah virus - in platelet concentrates by ultraviolet C light and in plasma by methylene blue plus visible light",10.1111/vox.12888,,,,"Background Emerging viruses like severe acute respiratory syndrome coronavirus (SARS-CoV), Crimean-Congo haemorrhagic fever virus (CCHFV) and Nipah virus (NiV) have been identified to pose a potential threat to transfusion safety. In this study, the ability of the THERAFLEX UV-Platelets and THERAFLEX MB-Plasma pathogen inactivation systems to inactivate these viruses in platelet concentrates and plasma, respectively, was investigated. Materials and methods Blood products were spiked with SARS-CoV, CCHFV or NiV, and then treated with increasing doses of UVC light (THERAFLEX UV-Platelets) or with methylene blue (MB) plus increasing doses of visible light (MB/light; THERAFLEX MB-Plasma). Samples were taken before and after treatment with each illumination dose and tested for residual infectivity. Results Treatment with half to three-fourths of the full UVC dose (0 center dot 2 J/cm(2)) reduced the infectivity of SARS-CoV (>= 3 center dot 4 log), CCHFV (>= 2 center dot 2 log) and NiV (>= 4 center dot 3 log) to the limit of detection (LOD) in platelet concentrates, and treatment with MB and a fourth of the full light dose (120 J/cm(2)) decreased that of SARS-CoV (>= 3 center dot 1 log), CCHFV (>= 3 center dot 2 log) and NiV (>= 2 center dot 7 log) to the LOD in plasma. Conclusion Our study demonstrates that both THERAFLEX UV-Platelets (UVC) and THERAFLEX MB-Plasma (MB/light) effectively reduce the infectivity of SARS-CoV, CCHFV and NiV in platelet concentrates and plasma, respectively.",2020,"Eickmann, Markus; Gravemann, Ute; Handke, Wiebke; Tolksdorf, Frank; Reichenberg, Stefan; Mueller, Thomas H.; Seltsam, Axel",Vox Sanguinis,3000244297,#4078,
,CZI,New SARS-like virus in China triggers alarm,10.1126/science.367.6475.234,,,,,2020,"Cohen, J.; Normile, D.",Science,2999883147,#197,
,CZI,New coronavirus threat galvanizes scientists,10.1126/science.367.6477.492,,32001631,,,2020,"Cohen, J.","Science (New York, N.Y.)",3004184096,#234,
,CZI,China virus response criticized as slow,10.1126/science.367.6478.606,,,,"As the novel coronavirus that emerged in Wuhan spreads worldwide (p. 610), China is facing criticism that its initial response was slow, and questions persist about officials' openness. People in and outside of China have praised an early warning about mysterious illnesses, sounded in a message sent 30 December 2019 by Li Wenliang, an ophthalmologist at a Wuhan hospital, to his medical school classmates. On 3 January, however, local police summoned Li, chastised him for spreading socially disruptive rumors, and made him sign a letter of self-criticism. He has since become infected and was hospitalized. Last week, the country's highest court faulted Li's detention as overreach. China is waging a fierce battle against the virus; it built a new, 1000-bed hospital in Wuhan in just 10 days, and Chinese scientists have published several papers on the virus. But in a 30 January statement leaked on social media, China's Ministry of Science and Technology urged researchers to pour their efforts into stopping its spread instead. “Until the task of prevention and control is completed, the focus should not be on the publication of papers,” the statement says As the novel coronavirus that emerged in Wuhan spreads worldwide (p. [610][1]), China is facing criticism that its initial response was slow, and questions persist about officials' openness. People in and outside of China have praised an early warning about mysterious illnesses, sounded in a message sent 30 December 2019 by Li Wenliang, an ophthalmologist at a Wuhan hospital, to his medical school classmates. On 3 January, however, local police summoned Li, chastised him for spreading socially disruptive rumors, and made him sign a letter of self-criticism. He has since become infected and was hospitalized. Last week, the country's highest court faulted Li's detention as overreach. China is waging a fierce battle against the virus; it built a new, 1000-bed hospital in Wuhan in just 10 days, and Chinese scientists have published several papers on the virus. But in a 30 January statement leaked on social media, China's Ministry of Science and Technology urged researchers to pour their efforts into stopping its spread instead. “Until the task of prevention and control is completed, the focus should not be on the publication of papers,” the statement says. > “Employees … are questioning whether they should post potentially life-saving info or check tweets first.” > > A September 2019 email by a National Weather Service official , reported by The Washington Post, after superiors rebuked forecasters for contradicting the president's inaccurate tweets about Hurricane Dorian's path. ### Agriculture The largest plague of desert locusts ( Schistocerca gregaria ) in decades is advancing across the Horn of Africa, consuming crops and threatening famine. The problem began in 2018 when unusually heavy rains on the Arabian Peninsula allowed populations to boom over several generations. In October 2019, the locusts swarmed south into Ethiopia, Eritrea, and Somalia, and in late December, they spread to Kenya, causing the worst infestation there in 70 years. Somalia—which last week declared a national emergency and asked for increased food aid—has already lost 100,000 hectares of crops and pasture. Another generation of locusts will likely hatch this month and cause more damage. The Food and Agriculture Organization of the United Nations called for $70 million to fight the outbreak with pesticides and help farmers. ### Glaciology After dropping sensors and a torpedo-shaped robot through a 700-meter hole in the ice, scientists in Antarctica last week revealed the first direct evidence that warm ocean temperatures around the rapidly retreating Thwaites Glacier could destabilize the key ice sheet. Researchers are worried because Thwaites—larger than the state of Illinois—helps block the ocean from reaching and warming the even bigger, unstable West Antarctic Ice Sheet, whose melting could eventually drive meters of sea level rise. Battling 2 months of stormy conditions, the team measured ocean waters beneath Thwaites at more than 2°C above the freezing point. The robot, Icefin (above, shown operating elsewhere in Antarctica), provided the first images of the glacier's grounding zone, the mysterious boundary where the floating coastal ice sheet attaches to bedrock. The project is part of the International Thwaites Glacier Collaboration, a multiyear effort by the United States and the United Kingdom that is wrapping up its first full field season. ### Leadership Some researchers in Colombia are calling for a little-known molecular biologist appointed as the country's first ever science minister to resign. They are outraged by reports that she treated cancer patients with a fungal extract, without running a formal clinical trial. “We can only regret that the course of how to do science in our country has been left in the hands of pseudoscience,” the Colombian Association of Medical Faculties wrote in a statement. In December 2019, Mabel Gisela Torres Torres was appointed to lead the newly created Ministry of Science, Technology and Innovation. In January, she told a newspaper she did not seek formal ethical, safety, and efficacy reviews of her work with patients because she believed the fungus posed no threat to human health. Her Ph.D. adviser has defended her and notes that metabolites in the fungi Torres studied have shown potential as a cancer treatment in cell and mouse studies. ### Environmental science ![Figure][2] CREDITS: (GRAPHIC) J. BRAINARD/ SCIENCE ; (DATA) UNITED NATIONS UNIVERSITY INSTITUTE FOR WATER, ENVIRONMENT, AND HEALTH The world's growing flows of wastewater offer a largely untapped, potentially lucrative source of energy, agricultural fertilizers, and water for irrigation, a comprehensive study says. The opportunities will increase as the annual volume of wastewater—now 380 billion cubic meters—expands by an estimated 51% by 2050, as populations and incomes multiply, says a team led by researchers at United Nations University's Institute for Water, Environment, and Health. About 13% of global demand for fertilizer could be met by recovering nitrogen, phosphorus, and potash from wastewater; such use provides a bonus, diverting nutrients from waterways, where they can create harmful eutrophication. Sewage also offers an alternative energy source. The need to plan and finance such recovery efforts is greatest in “low- and middle-income countries, where most municipal wastewater still goes into the environment untreated,” says the study, published 27 January in Natural Resources Forum. ### Conservation A decision by South Africa's government to allow breeding and genetic research on more than 30 wild species—including rhinos, lions, and cheetahs—could considerably reduce their genetic diversity, scientists warned last week. The government's action has been interpreted to allow breeders to select for commercially desirable traits, such as longer horns or larger body size; that could create genetic bottlenecks by promoting a few stud lines, the researchers wrote in the South African Journal of Science. They added that it may prove expensive or impossible to keep the intensively bred animals from mating with wild counterparts. A handful of game ranchers requested the policy, which South Africa announced in May 2019 without consulting the public or studying potential consequences. Game ranching —for hunting, meat, and tourism—already occupies more than 15% of the country, and the government wants to expand the industry. ### Funding The U.S. National Science Foundation (NSF) announced this week seven winners in its contest for “big ideas” to address societal problems. Four winning teams will receive $26,000 each to develop ideas on topics ranging from using artificial intelligence for complex problem-solving to developing small-scale technologies that sequester carbon dioxide. Three more teams earned $10,000 as runners-up. The 2026 Idea Machine contest attracted almost 800 submissions, and although some high schoolers made it to the semifinals, all the winners work at research institutions. NSF hopes to fund workshops and exploratory grants to further develop these and other ideas from contestants. ### Publishing A software company said last week it has teamed up with publishing giant Wiley to roll out in mid-2020 a tool that can signal whether findings in Wiley's scientific papers are reproducible. The software, called [Scite.ai][3], uses artificial intelligence to examine articles that cite a paper, and determines and displays whether they provide evidence supporting or contradicting the paper's findings. Users can browse and search the relevant text of the citing articles. Scite CEO Josh Nicholson says the software allows users to home in on articles that attempted to reproduce a study; of every 100 citations analyzed, Scite has found that 94 merely note the paper cited. The addition of Wiley's articles will expand Scite's current trove of more than 14 million papers from other publishers, most in the biomedical sciences. Nicholson expects his company to sign agreements with additional publishers to analyze their articles. ### Biomedicine The Chan Zuckerberg Initiative (CZI) said this week it will award $13.5 million to 30 patient advocacy groups to support their work finding treatments for rare diseases. Of an estimated 7000 rare diseases, fewer than 5% have treatments approved by the U.S. Food and Drug Administration. Each group will receive $450,000 over 2 years as well as training and mentoring as part of the foundation's Rare As One Project, launched last year to help advocates develop networks of patients, clinicians, and scientists. Most of the diseases are autoimmune, neurodegenerative, and other inherited disorders, but the list of diseases also includes rare cancers. CZI, founded by Facebook's Mark Zuckerberg and pediatrician Priscilla Chan, his wife, has made a few other awards to rare disease groups. The initiative expected to make just 10 Rare As One awards but tripled the number after receiving 275 applications. ### Conservation The Trump administration proposed last week to end penalties on owners of open oil storage ponds and other industrial operations that kill birds accidentally. The administration will instead encourage voluntary efforts to protect birds. Conservation groups cried foul, saying the change to the Migratory Bird Treaty Act of 1918 will only embolden companies to take actions that threaten vulnerable species. ### BRAIN Initiative gets leader Since its launch in 2013, the U.S. Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative has doled out about $1.3 billion to develop tools that map and manipulate the brain. Until now, the multiagency effort has had no formal director. But last week, neurobiologist John Ngai of the University of California, Berkeley, was named to take the helm in March. (A longer version of the interview is at .) > Q: Why is BRAIN getting a director? > A:The initiative has been run day to day by a terrific team of senior program directors and staff with oversight from the 10 [U.S. National Institutes of Health (NIH)] institutes and centers that are involved in BRAIN. I think as enterprises emerge from their startup phase, the question is how do you translate this into a sustainable enterprise, and yet maintain this cutting-edge innovation? … The initiative really will benefit from somebody thinking about this 24/7. > Q: What distinguishes this second phase of BRAIN? > A:In the first phase, there was a very intentional and concentrated focus on tool development. As we learn more about how neural circuits drive behavior … we can start implementing that knowledge, in terms of treating human diseases. I am hopeful that BRAIN, with other efforts in NIH and in partnership with industry, [can create] technology platforms that could be applied across multiple disease applications. For example: a toolkit of different types of viral delivery vectors [for gene therapy] that could be applied to different parts of the brain, different cell types in the brain, and so on. > Q: What do you see as the initiative's shortcomings? > A:We have a lot of figuring out to do in terms of how to balance the unique potential of individual investigator-initiated research versus the power of large-scale projects. … [And] there is a diversity issue in terms of ethnic diversity as well as gender diversity [among applicants and funded investigators]. It's a hard problem. It just kills me that we're leaving all this talent on the table. [1]: http://www.sciencemag.org/content/367/6478/610 [2]: pending:yes [3]: https://Scite.ai",2020,"Science, American Association for the Advancement of",,2103918422,#376,
,CZI,Will novel virus go pandemic or be contained?,10.1126/science.367.6478.610,,,,"The repatriation of 565 Japanese citizens from Wuhan, China, in late January offered scientists an unexpected opportunity to learn a bit more about the novel coronavirus (2019-nCoV) raging in that city. To avoid domestic spread of the virus, Japanese officials screened every passenger for disease symptoms and tested them for the virus after they landed. Eight tested positive, but four of those had no symptoms at all, says epidemiologist Hiroshi Nishiura of Hokkaido University, Sapporo—which is a bright red flag for epidemiologists who are trying to figure out what the fast-moving epidemic has in store for humanity. If many infections go unnoticed, as the Japanese finding suggests, that vastly complicates efforts to contain the outbreak. Two months after 2019-nCoV emerged—and with well over 20,000 cases and 427 deaths as Science went to press—mathematical modelers have been racing to predict where the virus will move next, how big a toll it might ultimately take, and whether isolating patients and limiting travel will slow it. But to make confident predictions, they need to know much more about how easily the virus spreads, how sick it makes people, and whether infected people with no symptoms can still infect others. Some of that information is coming out of China. But amid the all-out battle to control the virus, and with diagnostic capabilities in short supply, Chinese researchers cannot answer all the questions. Countries with just a handful of cases, such as Japan, can also reveal important data, says Preben Aavitsland of the Norwegian Institute of Public Health. “It's up to all countries now that receive cases to collect as much information as possible.” With the limited information so far, scientists are sketching out possible paths that the virus might take, weighing the likelihoods of each, and trying to determine the fallout. “We're at this stage where defined scenarios and the evidence for and against them are really important because it allows people to plan better,” says Marc Lipsitch, an epidemiologist at the Harvard T.H. Chan School of Public Health. These scenarios break into two broad categories: The world gets the virus under control—or it doesn't. The most optimistic scenario is one in which 2019-nCoV remains mostly confined to China, where 99% of the confirmed cases have occurred so far. (By 4 February, two dozen other countries had together reported 195 cases.) “There has obviously been a huge amount of spread within China, but [elsewhere], there's no evidence of any kind of substantial human-to-human transmission,” says Robin Thompson, a mathematical epidemiologist at the University of Oxford. “The risk probably isn't as high as some models have been projecting.” If no other countries see sustained transmission and the quarantines and other measures taken in China start to reduce the number of infections there, the risk of spread might gradually go down, and the virus might eventually be quashed. This happened with the severe acute respiratory syndrome (SARS) outbreak in 2003, which ended after fewer than 9000 cases. That's what the World Health Organization (WHO), which last week declared the outbreak a Public Health Emergency of International Concern, hopes for this time. In a press conference, Director-General Tedros Adhanom Ghebreyesus called for a global version of the approach his team took in the current Ebola outbreak: Fight the disease at the source and try to keep it from gaining a foothold elsewhere. “Focus on the epicenter,” Tedros said. “If you have several epicenters, it is chaos.” Epidemiologist Marion Koopmans of Erasmus Medical Center says it may not be that hard to contain the virus in a new locale as long as the first cases are detected and isolated early—provided the virus is not highly transmissible. “We don't see it taking off in the 200 or so cases seeded outside of China,” Koopmans says. If that pattern holds, “there still is the possibility it will bend off.” She and others suspect the climate may help. Influenza typically only spreads during the winter months and hits northern and southern China at different times. If that is true for 2019-nCoV, its spread might start to slow down in the Northern Hemisphere within a few months. “That is a big question mark we're trying to assess at the moment,” says Joseph Wu, a modeler at the University of Hong Kong. But is containment realistic? Success will depend in part on whether infected people who don't have symptoms can spread the virus. Asymptomatic people are hard to find and isolate, so if they can spread disease, 2019-nCoV “will be very difficult to stop in China,” says Alessandro Vespignani, a modeler of infectious diseases at Northeastern University. But if asymptomatic transmission is rare, he says, “isolation and social distancing can have a big impact.” So far it has been difficult to get a handle on this question. Some data from China seem to support asymptomatic transmission, but none are clear-cut. A widely reported 30 January letter in The New England Journal of Medicine described the case of a Chinese businesswoman who touched off a cluster of four cases in Germany before she became sick herself. But 4 days later, it became clear the researchers had not contacted the woman, who had flown back to China, before the paper was published. In a later phone interview, she said she had experienced some symptoms while in Germany. In follow-up results announced in a 4 February press release, the researchers noted that some patients they studied shed virus even though their symptoms were mild. That's almost as bad as asymptomatic transmission, says virologist Christian Drosten of the Charité University Hospital in Berlin: Patients with mild symptoms are unlikely to seek medical care and may not even stay home, giving the virus ample opportunities to spread far and wide. Based on what they have seen so far, many researchers think it's probably too late to contain the virus. “As the virus continues to spread in China, the risk of exportation to other countries grows and sooner or later we will see it spread in another country,” Aavitsland says. So far there has been no sustained transmission outside of China, but Lipsitch expects that to change: “I would be really shocked if in 2 or 3 weeks there wasn't ongoing transmission with hundreds of cases in several countries on several continents.” If the virus does spread to all corners of the world in a pandemic, several questions will loom large: What percentage of the population will become infected, and of those, how many will get very sick or die? More severe cases place heavier demands on health care systems—hospitals in Wuhan are already overwhelmed—and result in greater fears and disruption of daily life. A deadly pandemic might force the world to make stark choices about fair access to medicines or vaccines, if they become available. It might also lead to widespread restrictions on domestic travel akin to those already in force in China, Aavitsland says. If, on the other hand, 2019-nCoV resembles the common cold or a mild flu, the spread of the virus would be less alarming. Existing travel bans likely would be lifted. Understanding the severity and case fatality rate is a challenge with any new pathogen. When a new influenza strain emerged in 2009—and went on to cause a pandemic—many worried it might turn out to be a nasty variety. It took months to establish that the new virus killed only about one in 10,000 patients. So far, mortality among known 2019-nCoV cases is about 2%, and some reports say 20% of infected people suffer severe disease. But these figures may overlook tens of thousands of people with mild disease—say, a sore throat or a low-grade fever—who never seek medical care and may not even know they were infected with 2019-nCoV. Many may have no symptoms at all. “So what looks like a horrific disease may be the horrific tip of a very large iceberg,” Lipsitch says. The fact that four Japanese evacuees were asymptomatic is a case in point. Studies in China have also reported some cases with few or no symptoms. What's missing is a large study in China, Lipsitch says. He suggests some fraction of the tests that are available in a place with many cases should be set aside for that purpose. (Current recommendations in China call for testing people with clear symptoms only.) If indeed 2019-nCoV becomes pandemic, humanity may be stuck with it indefinitely. After spreading far and wide, the virus might become endemic in the human population, just like four other coronaviruses that cause the common cold, and occasionally cause fresh outbreaks. How much death and disease it would cause is anyone's guess. The silver lining of the epidemic is that scientists have collected and shared information at record speed. “Every day that goes by we know more and every day that goes by we can do better modeling,” Vespignani says. “Unfortunately, this beast is moving very fast.”",2020,"Kupferschmidt, Kai; Cohen, Jon",Science,3005524720,#400,
,CZI,News at a glance,10.1126/science.367.6479.720,,,,"Just weeks after a novel coronavirus emerged in Wuhan, China, the outbreak continued to expand in gravity and scope. This week, the cumulative death toll surpassed 1000, compared with the more than 800 killed by another coronavirus in the 2002–03 outbreaks of severe acute respiratory syndrome (SARS). Authorities assigned official names to the virus, SARS-CoV-2, and the resulting disease, COVID-19. Li Wenliang, a 34-year-old doctor who sounded an early alarm in Wuhan about the disease only to be summoned by local police for doing so, succumbed to the virus last week.",2020,Science,Science,2755115273,#819,
,CZI,Labs scramble to spot hidden coronavirus infections | Science | AAAS,10.1126/science.367.6479.727,,,,"The seeming precision of the global tallies of cases and deaths caused by the novel coronavirus now spreading from Wuhan, China belies an alarming fact. The world is in the dark about the epidemic’s real scale and speed, because existing tests have limited powers—and testing is far too spotty. “We are underestimating how common this infection is,” cautions Jeremy Farrar, head of the Wellcome Trust. Within days of Chinese researchers releasing the sequence of the virus on 11 January, scientists developed tests capable of detecting genetic sequences that distinguish the new agent from other coronaviruses circulating in humans. By 28 January, China’s National Medical Products Administration had approved diagnostic test kits from five companies. It was an astonishing pace for the response to a pathogen never seen before—and yet it was only a beginning.",2020,"Cohen, Jon; Kupferschmidt; Kai",,3006494401,#786,
,CZI,Labs scramble to produce new coronavirus diagnostics,10.1126/science.367.6479.727,,,,"The seeming precision of the global tallies of cases and deaths caused by the novel coronavirus now spreading from Wuhan, China, belies an alarming fact. The world is in the dark about the epidemic's real scale and speed, because existing tests have limited powers—and testing is far too spotty. “We are underestimating how common this infection is,” cautions Jeremy Farrar, head of the Wellcome Trust. Within days of Chinese researchers releasing the sequence of the virus on 11 January, scientists developed tests capable of detecting genetic sequences that distinguish the new agent from other coronaviruses circulating in humans. By 28 January, China's National Medical Products Administration had approved diagnostic test kits from five companies. It was an astonishing pace for the response to a pathogen never seen before—and yet it was only a beginning",2020,"Cohen, Jon; Kupferschmidt, Kai",Science,3006494401,#821,
,CZI,The health carer,10.1126/science.367.6479.730,,,,"On 2 January 2019, Tedros Adhanom Ghebreyesus faced a life-or-death decision. The director-general of the World Health Organization (WHO) had spent New Year's Eve in Bunia, Democratic Republic of the Congo (DRC), to boost the morale of staff fighting the second biggest Ebola epidemic ever. As he was getting ready to board a helicopter to Uganda, where he was scheduled to meet Prime Minister Ruhakana Rugunda, Tedros had to decide whether to bring along a young Congolese man named Charles Lwanga-Kikwaya. The day before, a group of Ebola vaccinators was attacked by a group of young men and women—one of many assaults WHO staff has had to endure—and Lwanga-Kikwaya had been hit on the head with a large stone. His injury was serious, says Jeremy Farrar, head of the Wellcome Trust, who accompanied Tedros and examined the patient. “We quickly decided we either had to evacuate him or he was going to die,” says Farrar, who trained as a neurologist.",2020,"Kupferschmidt, Kai",Science,3006481984,#820,
,CZI,Strategies shift as coronavirus pandemic looms,10.1126/science.367.6481.962,,,,"The virus may be spreading stealthily in many more places. A modeling group at Imperial College London has estimated that about two-thirds of the cases exported from China have yet to be detected. As Science went to press, the World Health Organization (WHO) still avoided using the word “pandemic” to describe the burgeoning crisis, instead talking about “epidemics in different parts of the world.” But many scientists say that regardless of what it's called, the window for containment is now almost certainly shut. “It looks to me like this virus really has escaped from China and is being transmitted quite widely,” says Christopher Dye, an epidemiologist at the University of Oxford. “I'm now feeling much more pessimistic that it can be controlled.” In the United States, “disruption to everyday life might be severe,” Nancy Messonnier, who leads the coronavirus response for the U.S. Centers for Disease Control and Prevention, warned on 25 February. “We are asking the American public to work with us to prepare for the expectation that this is going to be bad.”",2020,"Cohen, Jon; Kupferschmidt, Kai",Science,3006494401,#2658,
,CZI,Preprints bring ‘firehose’ of outbreak data,10.1126/science.367.6481.963,,,,"The Wu-han Clan is just one example of how the COVID-19 outbreak is transforming how scientists communicate about fast-moving health crises. A torrent of data is being released daily by preprint servers that didn't even exist a decade ago, then dissected on platforms such as Slack and Twitter, and in the media, before formal peer review begins. Journal staffers are working overtime to get manuscripts reviewed, edited, and published at record speeds. The venerable New England Journal of Medicine (NEJM) posted one COVID-19 paper within 48 hours of submission. Viral genomes posted on a platform named GISAID, more than 200 so far, are analyzed instantaneously by a phalanx of evolutionary biologists who share their phylogenetic trees in preprints and on social media.",2020,"Kupferschmidt, Kai",Science,,#2611,
,CZI,Can China's COVID-19 strategy work elsewhere?,10.1126/science.367.6482.1061,,32139521,,,2020,"Kupferschmidt, K.; Cohen, J.","Science (New York, N.Y.)",3005550222,#4786,
,CZI,The effect of travel restrictions on the spread of the 2019 novel coronavirus (COVID-19) outbreak,10.1126/science.aba9757,,32144116,,"Motivated by the rapid spread of COVID-19 in Mainland China, we use a global metapopulation disease transmission model to project the impact of travel limitations on the national and international spread of the epidemic. The model is calibrated based on internationally reported cases, and shows that at the start of the travel ban from Wuhan on 23 January 2020, most Chinese cities had already received many infected travelers. The travel quarantine of Wuhan delayed the overall epidemic progression by only 3 to 5 days in Mainland China, but has a more marked effect at the international scale, where case importations were reduced by nearly 80% until mid February. Modeling results also indicate that sustained 90% travel restrictions to and from Mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.",2020,"Chinazzi, M.; Davis, J. T.; Ajelli, M.; Gioannini, C.; Litvinova, M.; Merler, S.; Pastore, Y. Piontti A.; Mu, K.; Rossi, L.; Sun, K.; Viboud, C.; Xiong, X.; Yu, H.; Halloran, M. E.; Longini, I. M., Jr.; Vespignani, A.","Science (New York, N.Y.)",3006078464,#5137,
,CZI,Can an anti-HIV combination or other existing drugs outwit the new coronavirus?,10.1126/science.abb0659,,,,,2020,"Cohen, Jon",Science,3003329639,#242,
,CZI,Scientists are racing to model the next moves of a coronavirus that's still hard to predict | Science | AAAS,10.1126/science.abb2161,,,,"Beyond China itself, Thailand is the country that most likely will have people who arrive at one of its airports with an infection by the novel coronavirus (2019-nCoV) that has sickened more than 30,000 people. So says the latest update of a global risk assessment model created by a team of researchers from the Humboldt University of Berlin and the Robert Koch Institute that relies on air travel data.",2020,"Cohen, Jon",,3005441092,#553,
,CZI,Mission impossible? WHO director fights to prevent a pandemic without offending China | Science | AAAS,10.1126/science.abb2477,,,,"New outbreak comes as Tedros Adhanom Ghebreyesus struggles to raise more money, thwart Ebola, and fight health misinformation",2020,"Kupferschmidt, Kai",Science,3005563651,#609,
,CZI,Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation,10.1126/science.abb2507,,32075877,,"The outbreak of a novel betacoronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure (MCM) development, we determined a 3.5 Å-resolution cryo-EM structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also show biophysical and structural evidence that the 2019-nCoV S binds ACE2 with higher affinity than SARS-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable rapid development and evaluation of MCMs to address the ongoing public health crisis.",2020,"Wrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.; Goldsmith, Jory A.; Hsieh, Ching-Lin; Abiona, Olubukola; Graham, Barney S.; McLellan, Jason S.",Science,3005605085,#1461,
,CZI,Labs scramble to spot hidden coronavirus infections,10.1126/science.abb2651,,,,"The seeming precision of the global tallies of cases and deaths caused by the novel coronavirus now spreading from Wuhan, China belies an alarming fact. ... (A study group of the International Committee on Taxonomy of Viruses christened the novel virus severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, the same day). But many news stories have reported shortages of diagnostics in Hubei.",2020,"Jon Cohen, et al.",Science,3006483726,#663,
,CZI,Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2,10.1126/science.abb2762,,32132184,,"Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious epidemic COVID-19. Here we present cryo-EM structures of full-length human ACE2, in the presence of a neutral amino acid transporter B(0)AT1, with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 A, with a local resolution of 3.5 A at the ACE2-RBD interface. The ACE2-B(0)AT1 complex is assembled as a dimer of heterodimers, with the Collectrin-like domain (CLD) of ACE2 mediating homo-dimerization. The RBD is recognized by the extracellular peptidase domain (PD) of ACE2 mainly through polar residues. These findings provide important insights to the molecular basis for coronavirus recognition and infection.",2020,"Yan, R.; Zhang, Y.; Li, Y.; Xia, L.; Guo, Y.; Zhou, Q.","Science (New York, N.Y.)",2164706157,#5357,
,CZI,The costs of secrecy,10.1126/science.abb4420,,,,"""Without freedom of speech there is no modern world, just a barbaric one.” These words from China's most famous artist and activist, Ai Weiwei, have never been more important. Ai Weiwei would probably agree that China's actions in the coronavirus crisis require the voice of the scientific community, and he wouldn't be surprised that getting folks to say something has been a challenge. I didn't want to be the person to write this editorial. I felt that it would best come from someone inside China with a direct connection to the situation. Such a person could help dispel or reinforce the scraps of information coming from the intrepid journalists and the few courageous eyewitnesses. But over the past few weeks, I've been discouraged by the responses of such individuals who declined or didn't respond to an invitation to write a forthcoming editorial about China's secrecy on coronavirus. Some of these scientists and experts even expressed doubt that I'd find such a gutsy author at any organization in China to write such a piece.",2020,"Thorp, H. Holden",Science,245508297,#2531,
,CZI,China’s aggressive measures have slowed the coronavirus. They may not work in other countries,10.1126/science.abb5426,,,,"The question now is whether the world can take lessons from China’s apparent success—and whether the massive lockdowns and electronic surveillance measures imposed by an authoritarian government would work in other countries. “When you spend 20, 30 years in this business it’s like, ‘Seriously, you’re going to try and change that with those tactics?’” says Bruce Aylward, a Canadian WHO epidemiologist who led the international team and briefed journalists about its findings in Beijing and Geneva last week. “Hundreds of thousands of people in China did not get COVID-19 because of this aggressive response.”",2020,"Cohen, Kai Kupferschmidt; Jon",Science,,#3193,
,CZI,"Dog noses detect heat, the world faces coronavirus, and scientists search for extraterrestrial life",10.1126/science.abb5429,,,,"On this week’s show, Online News Editor David Grimm joins host Sarah Crespi to discuss how dogs’ cold noses may be able to sense warm bodies. Read the research. International News Editor Martin Enserink shares the latest from our reporters covering coronavirus. And finally, from a recording made at this year’s AAAS annual meeting, host Meagan Cantwell talks with Jill Tarter, chair emeritus at the SETI Institute, about the newest technologies being used to search for alien life, what a positive signal would look like, and how to inform the public if extraterrestrial life ever were detected. This week’s episode was produced with help from Podigy.",2020,"Crespi, Sarah",Science,2138505189,#5162,
,CZI,Indonesia finally reports two coronavirus cases. Scientists worry it has many more,10.1126/science.abb5653,,,,"Indonesia finally reported its first two COVID-19 cases on Monday. At a press conference in Jakarta, President Joko Widodo announced that two women aged 31 and 64 from Depok had contracted the virus. But some scientists believe the country, which has close ties to China, almost certainly has a “silent epidemic” within its borders and should urgently boost its surveillance efforts. Scientists at the Eijkman Institute for Molecular Biology tell Science they have offered to the Indonesian Ministry of Health to help test more people, but have been snubbed so far. The detection of the first two cases, along with measures to prevent the spread of the disease, demonstrate Indonesia’s seriousness and capability to deal with the COVID-19 epidemic, Widodo said yesterday. “Since the beginning, we have been serious in strictly following WHO [World Health Organization] guidelines regarding the coronavirus issue,” he said.",2020,"Rochmyaningsih, Dyna",Science,1990285966,#4995,
,CZI,‘We had to act.’ How coronavirus fears forced physics society to nix giant meeting,10.1126/science.abb5683,,,,"Harold Dorwin/Center for Astrophysics/Harvard & Smithsonian The March Meeting of the American Physical Society (APS) wasn’t the first event canceled for fear of the coronavirus, but it was nixed in dramatic fashion.",2020,"Cho, Adrian",Sccience,,#3627,
,CZI,"With $115 million, more than 80 Boston researchers will collaborate to tackle COVID-19",10.1126/science.abb6021,,,,"A $115 million collaboration to tackle the rapidly spreading viral disease COVID-19, led by heavy hitters of Boston science and funded by a Chinese property development company, kicked off today as the group’s leaders pledged to take on the virus on many fronts. The project brings together researchers at many of the city’s top academic institutions, along with local biotechnology companies such as Moderna. Those leading it hope they can quickly funnel money into studies that will build off a new repository of samples from infected people and community surveillance, materials that can be rapidly shared among scientists. The project, they anticipate, should answer critical questions about how COVID-19 is spreading and how best to prevent and treat infections.",2020,"Couzin-Frankel, Jennifer",Science,2161064841,#4594,
,CZI,Why airport screening won’t stop the spread of coronavirus,10.1126/science.abb6136,,,,"If you have traveled internationally the past 2 months, you may have encountered them: health officers briefly pointing a thermometer gun at your forehead or watching as you go by to check for signs of a cough or difficulty breathing. Many countries are now watching arriving and departing air passengers who might suffer from the viral disease COVID-19; some require passengers to fill out health declarations. (Some also simply ban or quarantine those who have recently been in outbreak hot spots.) Exit and entry screening may look reassuring, but experience with other diseases shows it’s exceedingly rare for screeners to detect infected passengers. Just last week, eight passengers who later tested positive for COVID-19 arrived in Shanghai from Italy and passed the airport screeners unnoticed, for example. And even if screeners do find the occasional case, it has almost no impact on the course of an outbreak.",2020,"Normile, Dennis",Science,,#4929,
,CZI,"Quarantined at home now, U.S. scientist describes his visit to China’s hot zone",10.1126/science.abb6154,,,,"On 13 February, Clifford Lane went to a Washington, D.C.–area airport to catch a flight to Japan, where he would help launch a study of an experimental drug, remdesivir, against coronavirus disease 2019 (COVID-19). Lane is a deputy director at the U.S. National Institute of Allergy and Infectious Diseases and a right-hand man to Anthony Fauci, head of NIAID and the top research scientist in the country advising the White House on the outbreak of the virus. As Lane waited to board his plane, he was told that his final destination had changed. “I get an email, ‘You need to go to China.’ It’s like, are you kidding?” Lane had been selected as one of two U.S. scientists to join a World Health Organization team of 13 international researchers who would tour five different cities with 12 Chinese colleagues to get a firsthand look at the coronavirus epidemic there. The joint mission, which ran from 16–23 February led to a report that offered more details about the clinical course of COVID-19 and the epidemiology in China than had appeared anywhere before.",2020,"Cohen, Jon",Science,,#5151,
,CZI,Coronavirus disruptions could hurt North Korea’s efforts to treat tuberculosis,10.1126/science.abb6184,,,,"North Korea watchers warn that the country’s aggressive measures to defend itself against COVID-19, the illness caused by the novel coronavirus, are hobbling efforts to combat tuberculosis (TB) and other infectious diseases. Sandwiched between two COVID-19 hot spots—China and South Korea—North Korea at the end of January suspended international flights and severed its rail link with China. Since then, cargo containers headed to North Korea’s port in Nampo have stalled in Dalian, China, snagged on red tape in China and new quarantine procedures in Nampo. The only way in and out of North Korea now is a road crossing on its northern border with China. North Korea’s state media has said the border restrictions will remain in effect until COVID-19 has stopped spreading or a vaccine is available. That puts North Korea’s thousands of TB patients in a precarious situation. Three containers with first-line TB drugs are among hundreds held up in Dalian, says a U.S.-based humanitarian organization official, who requested anonymity. The official notes that North Korea’s supply of first-line TB drugs is expected to run out in May or June. The situation is even more perilous for North Koreans infected with multidrug-resistant TB strains. Treatment lapses can lead to even more recalcitrant strains. “Truly it opens grave concern” about the development of extensively drug-resistant TB in North Korea, the official says. Related",2020,"Stone, Richard",Science,,#5245,
,CZI,"Top stories: Bungled coronavirus testing, disarming ‘atomic bomb’ cells, and jet stream blocking",10.1126/science.abb6188,,,,"Speed is critical in the response to COVID-19. So why has the United States been so slow in its attempt to develop reliable diagnostic tests and use them widely? One answer is that a test kit designed by the U.S. Centers for Disease Control and Prevention (CDC) and rolled out to state and local labs late last month contained a faulty reagent. The problems have led many to doubt the accuracy of confirmed tallies of the disease. But the situation may soon improve, as the Food and Drug Administration comes up with a workaround for the faulty CDC kit.",2020,"Pérez Ortega, Rodrigo",Science,,#4962,
,CZI,Maybe not an overreaction,10.1126/scitranslmed.aba9019,,,,"A mathematical simulation of coronavirus COVID-19 estimated the number of infections to be far worse than reported. Starting in December 2019, a novel coronavirus, known as COVID-19, caused growing cases of atypical pneumonia in the city of Wuhan, China. The virus spread. As of 12 February 2020, a total of 45,204 confirmed cases had been reported from China and 519 confirmed cases from 27 countries worldwide. Among the reported victims, 1116 died. When facing an epidemic as such, a dangerous mistake that countries over the world can make is to rely entirely on confirmed data but underestimate the actual size of infections. Causes of underestimation include the limitation of resources, as there can be insufficient quarantine spaces, detection reagents, and medical personnel to identify infections in real time. Additionally, the lack of symptoms from the virus in its dormant state can delay confirmation. There is also a fear of data being manipulated or downplayed by officials due to economic and political concerns.",2020,"Han, Li-Hsin",,3005971507,#772,
,CZI,Antiviral Theatrics?,10.1126/scitranslmed.abb2600,,,,"This, though, is an official organ of the Chinese state – none more so – showing all sorts of white-fog-spraying devices being deployed outdoors, with the caption “Full-front disinfection work has started in #Wuhan, an effort to contain the spread of #coronavirus“. ... Maybe there’s something in the mix that someone thinks will do some good against coronavirus particles – I doubt if they’re correct, if so – or maybe the whole thing is just meant to show that the Authorities Are Doing Something.",2020,"Lowe, Derek",Science,2995332254,#698,
,CZI,Negative Nasopharyngeal and Oropharyngeal Swab Does Not Rule Out COVID-19,10.1128/jcm.00297-20,,32102856,,"Coronavirus Disease 19 (COVID-19), has become the Public Health Emergency of International Concern.....",2020,"Winichakoon, P.; Chaiwarith, R.; Liwsrisakun, C.; Salee, P.; Goonna, A.; Limsukon, A.; Kaewpoowat, Q.",Journal of clinical microbiology,2134211166,#2974,
,CZI,"Improved molecular diagnosis of COVID-19 by the novel, highly sensitive and specific COVID-19-RdRp/Hel real-time reverse transcription-polymerase chain reaction assay validated in vitro and with clinical specimens",10.1128/jcm.00310-20,,32132196,,"On 31st December 2019, the World Health Organization was informed of a cluster of cases of pneumonia of unknown etiology in Wuhan, China. Subsequent investigations identified a novel coronavirus, now named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from the affected patients. Highly sensitive and specific laboratory diagnostics are important for controlling the rapidly evolving SARS-CoV-2-associated Coronavirus Disease 2019 (COVID-19) epidemic. In this study, we developed and compared the performance of three novel real-time RT-PCR assays targeting the RNA-dependent RNA polymerase (RdRp)/helicase (Hel), spike (S), and nucleocapsid (N) genes of SARS-CoV-2 with that of the reported RdRp-P2 assay which is used in >30 European laboratories. Among the three novel assays, the COVID-19-RdRp/Hel assay had the lowest limit of detection in vitro (1.8 TCID50/ml with genomic RNA and 11.2 RNA copies/reaction with in vitro RNA transcripts). Among 273 specimens from 15 patients with laboratory-confirmed COVID-19 in Hong Kong, 77 (28.2%) were positive by both the COVID-19-RdRp/Hel and RdRp-P2 assays. The COVID-19-RdRp/Hel assay was positive for an additional 42 RdRd-P2-negative specimens [119/273 (43.6%) vs 77/273 (28.2%), P<0.001], including 29/120 (24.2%) respiratory tract specimens and 13/153 (8.5%) non-respiratory tract specimens. The mean viral load of these specimens was 3.21*104 RNA copies/ml (range, 2.21*102 to 4.71*105 RNA copies/ml). The COVID-19-RdRp/Hel assay did not cross-react with other human-pathogenic coronaviruses and respiratory pathogens in cell culture and clinical specimens, whereas the RdRp-P2 assay cross-reacted with SARS-CoV in cell culture. The highly sensitive and specific COVID-19-RdRp/Hel assay may help to improve the laboratory diagnosis of COVID-19.",2020,"Chan, Jasper Fuk-Woo; Yip, Cyril Chik-Yan; To, Kelvin Kai-Wang; Tang, Tommy Hing-Cheung; Wong, Sally Cheuk-Ying; Leung, Kit-Hang; Fung, Agnes Yim-Fong; Ng, Anthony Chin-Ki; Zou, Zijiao; Tsoi, Hoi-Wah; Choi, Garnet Kwan-Yue; Tam, Anthony Raymond; Cheng, Vincent Chi-Chung; Chan, Kwok-Hung; Tsang, Owen Tak-Yin; Yuen, Kwok-Yung",Journal of clinical microbiology,2575652810,#5099,
,CZI,Suggestions casted to the novel coronavirus nucleic acid amplification test from viral pneumonia pathogenesis,10.1128/JCM.00490-15,,,,"An outbreak of Novel Coronavirus (2019-nCoV), results in Coronavirus disease that began in Wuhan, China, has spread rapidly with cases now confirmed in multiple countries. Nucleic acid amplification test (NAAT), represent by reverse-transcriptase polymerase chain reaction (RT-PCR) plays an important role in disease diagnosis and treatment evaluation. The test results by RT-PCR have attracted much attention recently. As understanding to this novel pathogen is still limited, it would be much help to combine the knowledge about its pathogenesis to judge the test results, in addition to review the quality control in laboratory. This review will focus on understanding the specific RT-PCR performance of the 2019-nCoV, under the background of viral pneumonia. The purpose of this review is to add value to NAAT of 2019-nCoV, with combined knowledge of epidemiology, pathogenesis, clinical characteristics and pre-analysis quality control from viral pneumonia.",2020,"ZHAO, Xiuying",Chinese Journal of Laboratory Medicine,1829288473,#2052,
,CZI,Analysis of false-negative results for 2019 novel coronavirus nucleic acid test and related countermeasures,10.1128/JCM.00490-15,,,,"In December 2019, a cluster of patients with pneumonia of unknown cause were linked to a seafood wholesale market in Wuhan, China. Some studies found that the virus was a new kind of virus which had never been found in the human body. Then, the virus was named 2019 Novel Coronavirus (2019-nCoV) by the World Health Organization (WHO). 2019-nCoV nucleic acid detection is one of the essential indicators of NCP (Novel Coronavirus Pneumonia). Recently, some false-negative cases in China-Japan Friendship Hospital and Hangzhou Hospital led the clinical doctors to question the value of the nucleic acid detection. In this paper, more than 3 000 results of 2019-nCoV detection in Zhongnan Hospital, Wuhan University were analyzed. Attention should be paid to the root cause of false-negative results and the related countermeasures should be taken.",2020,"LI, Jin; YE, Guangming; CHEN, Liangjun; WANG, Jiajun; LI, Yirong",Chinese Journal of Laboratory Medicine,1829288473,#2209,
,CZI,Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS,10.1128/JVI.00127-20,,,,"Recently a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by SARS coronavirus (SARS-CoV). Since SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV's capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV, and may help epidemic surveillance and preventive measures against 2019-nCoV.SignificanceThe recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002-2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.",2020,"Wan, Yushun; Shang, Jian; Graham, Rachel; Baric, Ralph S.; Li, Fang",Journal of Virology,3004348779,#46,
,CZI,Molecular Basis of Binding between Middle East Respiratory Syndrome Coronavirus and CD26 from Seven Bat Species,10.1128/JVI.01387-19,,,,"Continued reports of Middle East respiratory syndrome coronavirus (MERS-CoV) infecting humans have occurred since the identification of this virus in 2012. MERS-CoV is prone to cause endemic disease in the Middle East, with several dozen spillover infections to other continents. It is hypothesized that MERS-CoV originated from bat coronaviruses and that dromedary camels are its natural reservoir. Although gene segments identical to MERS-CoV were sequenced from certain species of bats and one species experimentally shed the virus, it is still unknown whether other bats can transmit the virus. Here, at the molecular level, we found that all purified bat CD26s (bCD26s) from a diverse range of species interact with the receptor binding domain (RBD) of MERS-CoV, with equilibrium dissociation constant values ranging from several to hundreds at the micromolar level. Moreover, all bCD26s expressed in this study mediated the entry of pseudotyped MERS-CoV to receptor-expressing cells, indicating the broad potential engagement of bCD26s as MERS-CoV receptors. Further structural analysis indicated that in the bat receptor, compared to the human receptor, substitutions of key residues and their adjacent amino acids leads to decreased binding affinity to the MERS-RBD. These results add more evidence to the existing belief that bats are the original source of MERS-CoV and suggest that bCD26s in many species can mediate the entry of the virus, which has significant implications for the surveillance and control of MERS-CoV infection.IMPORTANCE In this study, we found that bat CD26s (bCD26s) from different species exhibit large diversities, especially in the region responsible for binding to the receptor binding domain (RBD) of Middle East respiratory syndrome coronavirus (MERS-CoV). However, they maintain the interaction with MERS-RBD at varied affinities and support the entry of pseudotyped MERS-CoV. These bat receptors polymorphisms seem to confer evolutionary pressure for the adaptation of CD26-binding virus, such as the ancestor of MERS-CoV, and led to the generation of diversified CD26-engaging CoV strains. Thus, our data add more evidence to support that bats are the reservoir of MERS-CoV and similar viruses, as well as further emphasize the necessity to survey MERS-CoV and other CoVs among bats.",2020,"Yuan, Yuan; Qi, Jianxun; Peng, Ruchao; Li, Chunrui; Lu, Guangwen; Yan, Jinghua; Wang, Qihui; Gao, George Fu",Journal of Virology,2991340753,#2071,
,CZI,Molecular Basis of Binding between Middle East Respiratory Syndrome Coronavirus and CD26 from Seven Bat Species Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection,10.1128/jvi.01387-19 10.1128/mBio.02764-19,,,,"Continued reports of Middle East respiratory syndrome coronavirus (MERS-CoV) infecting humans have occurred since the identification of this virus in 2012. MERS-CoV is prone to cause endemic disease in the Middle East, with several dozen spillover infections to other continents. It is hypothesized that MERS-CoV originated from bat coronaviruses and that dromedary camels are its natural reservoir. Although gene segments identical to MERS-CoV were sequenced from certain species of bats and one species experimentally shed the virus, it is still unknown whether other bats can transmit the virus. Here, at the molecular level, we found that all purified bat CD26s (bCD26s) from a diverse range of species interact with the receptor binding domain (RBD) of MERS-CoV, with equilibrium dissociation constant values ranging from several to hundreds at the micromolar level. Moreover, all bCD26s expressed in this study mediated the entry of pseudotyped MERS-CoV to receptor-expressing cells, indicating the broad potential engagement of bCD26s as MERS-CoV receptors. Further structural analysis indicated that in the bat receptor, compared to the human receptor, substitutions of key residues and their adjacent amino acids leads to decreased binding affinity to the MERS-RBD. These results add more evidence to the existing belief that bats are the original source of MERS-CoV and suggest that bCD26s in many species can mediate the entry of the virus, which has significant implications for the surveillance and control of MERS-CoV infection.IMPORTANCE In this study, we found that bat CD26s (bCD26s) from different species exhibit large diversities, especially in the region responsible for binding to the receptor binding domain (RBD) of Middle East respiratory syndrome coronavirus (MERS-CoV). However, they maintain the interaction with MERS-RBD at varied affinities and support the entry of pseudotyped MERS-CoV. These bat receptors polymorphisms seem to confer evolutionary pressure for the adaptation of CD26-binding virus, such as the ancestor of MERS-CoV, and led to the generation of diversified CD26-engaging CoV strains. Thus, our data add more evidence to support that bats are the reservoir of MERS-CoV and similar viruses, as well as further emphasize the necessity to survey MERS-CoV and other CoVs among bats. Coronaviruses (CoVs) are common human and animal pathogens that can transmit zoonotically and cause severe respiratory disease syndromes. CoV infection requires spike proteins, which bind viruses to host cell receptors and catalyze virus-cell membrane fusion. Several CoV strains have spike proteins with two receptor-binding domains, an S1A that engages host sialic acids and an S1B that recognizes host transmembrane proteins. As this bivalent binding may enable broad zoonotic CoV infection, we aimed to identify roles for each receptor in distinct infection stages. Focusing on two betacoronaviruses, murine JHM-CoV and human Middle East respiratory syndrome coronavirus (MERS-CoV), we found that virus particle binding to cells was mediated by sialic acids; however, the transmembrane protein receptors were required for a subsequent virus infection. These results favored a two-step process in which viruses first adhere to sialic acids and then require subsequent engagement with protein receptors during infectious cell entry. However, sialic acids sufficiently facilitated the later stages of virus spread through cell-cell membrane fusion, without requiring protein receptors. This virus spread in the absence of the prototype protein receptors was increased by adaptive S1A mutations. Overall, these findings reveal roles for sialic acids in virus-cell binding, viral spike protein-directed cell-cell fusion, and resultant spread of CoV infections.IMPORTANCE CoVs can transmit from animals to humans to cause serious disease. This zoonotic transmission uses spike proteins, which bind CoVs to cells with two receptor-binding domains. Here, we identified the roles for the two binding processes in the CoV infection process. Binding to sialic acids promoted infection and also supported the intercellular expansion of CoV infections through syncytial development. Adaptive mutations in the sialic acid-binding spike domains increased the intercellular expansion process. These findings raise the possibility that the lectin-like properties of many CoVs contribute to facile zoonotic transmission and intercellular spread within infected organisms.",2020,"Yuan, Yuan; Qi, Jianxun; Peng, Ruchao; Li, Chunrui; Lu, Guangwen; Yan, Jinghua; Wang, Qihui; Gao, George Fu; Qing, Enya; Hantak, Michael; Perlman, Stanley; Gallagher, Tom",Journal of Virology,2991340753,#2070,
,CZI,Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection,10.1128/JVI.01774-19,,,,"Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding in a new host. Our previous work with severe acute respiratory syndrome (SARS)-like viruses argued that bats already harbor CoVs with the ability to infect humans without adaptation. These results suggested that additional barriers limit the emergence of zoonotic CoV. In this work, we describe overcoming host restriction of two Middle East respiratory syndrome (MERS)-like bat CoVs using exogenous protease treatment. We found that the spike protein of PDF2180-CoV, a MERS-like virus found in a Ugandan bat, could mediate infection of Vero and human cells in the presence of exogenous trypsin. We subsequently show that the bat virus spike can mediate the infection of human gut cells but is unable to infect human lung cells. Using receptor-blocking antibodies, we show that infection with the PDF2180 spike does not require MERS-CoV receptor DPP4 and antibodies developed against the MERS spike receptor-binding domain and S2 portion are ineffective in neutralizing the PDF2180 chimera. Finally, we found that the addition of exogenous trypsin also rescues HKU5-CoV, a second bat group 2c CoV. Together, these results indicate that proteolytic cleavage of the spike, not receptor binding, is the primary infection barrier for these two group 2c CoVs. Coupled with receptor binding, proteolytic activation offers a new parameter to evaluate the emergence potential of bat CoVs and offers a means to recover previously unrecoverable zoonotic CoV strains.IMPORTANCE Overall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential and risk posed by zoonotic coronaviruses. In addition, the findings also offer a novel means to recover previously uncultivable zoonotic coronavirus strains and argue that other tissues, including the digestive tract, could be a site for future coronavirus emergence events in humans.",2020,"Menachery, Vineet D.; Dinnon, Kenneth H.; Yount, Boyd L.; McAnarney, Eileen T.; Gralinski, Lisa E.; Hale, Andrew; Graham, Rachel L.; Scobey, Trevor; Anthony, Simon J.; Wang, Lingshu; Graham, Barney; Randell, Scott H.; Lipkin, W. Ian; Baric, Ralph S.",Journal of Virology,2994156659,#2167,
,CZI,Nucleocapsid Protein Recruitment to Replication-Transcription Complexes Plays a Crucial Role in Coronaviral Life Cycle,10.1128/JVI.01925-19,,,,"Coronavirus (CoV) nucleocapsid (N) proteins are key for incorporating genomic RNA into progeny viral particles. In infected cells, N proteins are present at the replication-transcription complexes (RTCs), the sites of CoV RNA synthesis. It has been shown that N proteins are important for viral replication and that the one of mouse hepatitis virus (MHV), a commonly used model CoV, interacts with nonstructural protein 3 (nsp3), a component of the RTCs. These two aspects of the CoV life cycle, however, have not been linked. We found that the MHV N protein binds exclusively to nsp3 and not other RTC components by using a systematic yeast two-hybrid approach, and we identified two distinct regions in the N protein that redundantly mediate this interaction. A selective N protein variant carrying point mutations in these two regions fails to bind nsp3 in vitro, resulting in inhibition of its recruitment to RTCs in vivo. Furthermore, in contrast to the wild-type N protein, this N protein variant impairs the stimulation of genomic RNA and viral mRNA transcription in vivo and in vitro, which in turn leads to impairment of MHV replication and progeny production. Altogether, our results show that N protein recruitment to RTCs, via binding to nsp3, is an essential step in the CoV life cycle because it is critical for optimal viral RNA synthesis.IMPORTANCE CoVs have long been regarded as relatively harmless pathogens for humans. Severe respiratory tract infection outbreaks caused by severe acute respiratory syndrome CoV and Middle East respiratory syndrome CoV, however, have caused high pathogenicity and mortality rates in humans. These outbreaks highlighted the relevance of being able to control CoV infections. We used a model CoV, MHV, to investigate the importance of the recruitment of N protein, a central component of CoV virions, to intracellular platforms where CoVs replicate, transcribe, and translate their genomes. By identifying the principal binding partner at these intracellular platforms and generating a specific mutant, we found that N protein recruitment to these locations is crucial for promoting viral RNA synthesis. Moreover, blocking this recruitment strongly inhibits viral infection. Thus, our results explain an important aspect of the CoV life cycle and reveal an interaction of viral proteins that could be targeted in antiviral therapies.",2020,"Cong, Yingying; Ulasli, Mustafa; Schepers, Hein; Mauthe, Mario; V’kovski, Philip; Kriegenburg, Franziska; Thiel, Volker; de Haan, Cornelis A. M.; Reggiori, Fulvio",Journal of Virology,2989769422,#2317,
,CZI,Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry,10.1128/JVI.02015-19,,,,"Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies.IMPORTANCE Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.",2020,"Wan, Yushun; Shang, Jian; Sun, Shihui; Tai, Wanbo; Chen, Jing; Geng, Qibin; He, Lei; Chen, Yuehong; Wu, Jianming; Shi, Zhengli; Zhou, Yusen; Du, Lanying; Li, Fang",Journal of Virology,2995449088,#10,
,CZI,Strategies against the novel coronavirus: Possible applications of the experimental Ebola drug remdesivir are being tested,10.1128/JVI.03050-13,,,,,2020,,Deutsche Apotheker Zeitung,1967666468,#2472,
,CZI,Emergency response plan for the neonatal intensive care unit during epidemic of 2019 novel coronavirus,10.1136/archdischild-2018-316336,,32051072,,"2019 novel coronavirus (2019-nCoV) infection has been spreading in China since December 2019. Neonates are presumably the high-risk population susceptible to 2019-nCoV due to immature immune function. The neonatal intensive care unit (NICU) should be prepared for 2019-nCoV infections as far as possible. The emergency response plan enables the efficient response capability of NICU. During the epidemic of 2019-nCoV, the emergency response plan for the NICU should be based on the actual situation, including diagnosis, isolation, and treatment, as well as available equipment and staffing, and take into account the psychosocial needs of the families and neonatal care staff.",2020,"Pediatric Committee, Medical Association of Chinese People′s Liberation Army; Editorial Committee of Chinese Journal of Contemporary, Pediatrics",Zhongguo Dang Dai Er Ke Za Zhi,2917076901,#812,
,CZI,Novel Coronavirus disease 2019 (COVID-19): The importance of recognising possible early ocular manifestation and using protective eyewear,10.1136/bjophthalmol-2020-315994,,32086236,,,2020,"Li, Ji-Peng Olivia; Lam, Dennis Shun Chiu; Chen, Youxin; Ting, Daniel Shu Wei",Br J Ophthalmol,3006602665,#1591,
,CZI,China coronavirus: cases surge as official admits human to human transmission,10.1136/bmj.m236,,,,,2020,"Parry, J.",BMJ (Clinical research ed.),3000039309,#152,
,CZI,China coronavirus: what do we know so far?,10.1136/bmj.m308,,,,,2020,"Mahase, E.",BMJ (Clinical research ed.),3001211201,#151,
,CZI,The psychological effects of quarantining a city,10.1136/bmj.m313,,,,"Whether the epidemiological benefits of mandatory mass quarantine outweigh the psychological costs is a judgement that should not be made lightlyThe emergence of a novel form of coronavirus in Wuhan, China, is creating a confused and rapidly evolving situation. As ever in the early stages of a major incident, facts are unclear. We’re not sure how many people have caught the disease, the fatality rate, the incubation period, how far it’s spread—or how worried we should be. The imposition of travel restrictions on Wuhan—and an expanding number of other cities—has surprised many. The move has left over 20 million people caught in a modern form of quarantine. Regardless of whether it succeeds in controlling the outbreak, the widespread lockdown will inevitably have a psychological effect. Not surprisingly, the UK media are already reporting the emotional impact of both the outbreak and the response. Residents are said to be comparing the situation to “the end of the world,” hospitals are “overwhelmed,” and there are concerns about food shortages. “Panic in Wuhan” is commonly reported.We must be careful of …",2020,"Rubin, G. James; Wessely, Simon",BMJ,3003379403,#163,
,CZI,"China coronavirus: mild but infectious cases may make it hard to control outbreak, report warns",10.1136/bmj.m325,,,,"Uncertainty over the severity spectrum of the novel coronavirus (2019-nCoV) and whether people with mild symptoms can efficiently transmit the virus mean it is currently “unclear” whether the outbreak can be contained within China, a report from Imperial College London has warned.1The update from the MRC Centre for Global Infectious Disease Analysis said that the rate of transmission could come down as people become aware of the threat and try to avoid becoming infected, as happened with severe acute respiratory syndrome (SARS).But it raised concerns over reports of mildly symptomatic but infectious cases, which were not a feature of SARS. Detecting and …",2020,"Mahase, Elisabeth",BMJ,3003233446,#180,
,CZI,Chinese premier rallies medics in coronavirus fight,10.1136/bmj.m343,,,,"Xinhua/Li Tao/PAChina’s premier, Li Keqiang (centre), visited the Wuhan Jinyintan Hospital this week to see the team’s work to control the outbreak of the novel coronavirus in the area.Li arrived on 27 January …",2020,"Moberly, Tom",BMJ,3003294398,#178,
,CZI,"Following the evidence, from coronavirus to terrorism response",10.1136/bmj.m344,,,,"The emergence of a novel coronavirus has led China to impose travel restrictions around Wuhan and other cities (doi:10.1136/bmj.m349). Yet, as G James Rubin and Simon Wessely point out (doi:10.1136/bmj.m313), we don’t not know whether the potential benefits of mandatory mass quarantine outweigh the psychological costs of such an intervention to the people affected. Elisabeth Mahase summarises what we know so far about the virus and its effects (doi:10.1136/bmj.m308); clearly there is much we …",2020,"Moberly, Tom",BMJ,3003277976,#179,
,CZI,"China coronavirus: partial border closures into Hong Kong are not enough, say doctors",10.1136/bmj.m349,,,,"As the novel coronavirus (2019-nCOV) outbreak rapidly expands across the border in mainland China, healthcare workers in Hong Kong are bracing for a potential explosion of cases locally and have urged the government to severely restrict arrivals from mainland China or even to close the border completely.Eight cases were confirmed in Hong Kong as of 27 January, and 38% of the 663 beds in the negative pressure wards, which are used to isolate patients at public hospitals, were already in use, said officials. They expressed concern that the public health system might be overwhelmed if a local “super-spreader” event occurs or by people from mainland China coming into Hong Kong to seek treatment.On 28 January Carrie Lam, Hong Kong chief executive, announced a partial border closure, halting all cross border rail routes from midnight on 30 January, as well as a suspension of six border checkpoints, suspension of ferries, gradual reduction of cross border flights from 480 a …",2020,"Parry, Jane",BMJ,3004279122,#175,
,CZI,Wuhan: Britons to be evacuated as scientists estimate 44 000 cases of 2019-nCOV in the city,10.1136/bmj.m351,,31996342,,,2020,"Parry, J.",BMJ (Clinical research ed.),3003684729,#86,
,CZI,Coronavirus shows how UK must act quickly before being shut out of Europe’s health protection systems,10.1136/bmj.m400,,,,"The threat posed by 2019-nCoV and the fragmentation of existing health protection systems caused by Brexit call for urgent assessment of cross Europe cooperation, say Mark Flear, Anniek de Ruijter, and Martin McKeeHealth authorities worldwide are racing to contain the spread of the coronavirus 2019-nCoV, identified as the cause of the outbreak that began in Wuhan, China, at the end of last year. By 31 January more than 9600 people were reported to have been infected in China, with around 200 deaths, and cases have also been reported elsewhere in Asia and in North America, Australia, and Europe, including France, Finland, Germany, and now the UK.1 The case in Germany is especially worrying as it was in someone who had not travelled to China but who had been in contact with someone who had. Unprecedented measures, including lockdowns of large cities in China and widespread flight cancellations, are being adopted.The international response to major outbreaks of infectious disease is coordinated by the World Health Organization and is based on its International Health Regulations.2 Europe also has a regime for communicable disease control,3 centred on the Stockholm based European Centre for Disease Prevention and Control (ECDC), which has a crucial role in responding to threats to health in the continent.Given the UK’s departure from the European Union, we argue that the coronavirus outbreak is an urgent warning highlighting the need to reflect on what Brexit might mean for the country’s health security. We review how that system operates and what the implications might be for the UK. In doing so we draw on the experience of Switzerland. Like a post-Brexit UK, Switzerland is outside …",2020,"Flear, Mark; de Ruijter, Anniek; McKee, Martin",BMJ,,#196,
,CZI,Response to the emerging novel coronavirus outbreak,10.1136/bmj.m406,,32005675,,,2020,"Kickbusch, I.; Leung, G.",BMJ (Clinical research ed.),3003585850,#96,
,CZI,China coronavirus: WHO declares international emergency as death toll exceeds 200,10.1136/bmj.m408,,,,"The World Health Organization has declared the current novel coronavirus (2019-nCoV) outbreak to be a public health emergency of international concern, as latest figures show that nearly 10 000 people have been infected and that over 200 have died.WHO’s emergency committee reconvened on 30 January—a week after it first met—to reassess the situation. Tedros Adhanom Ghebreyesus, WHO director general, said that the declaration was “not because of what is happening in China but because of what is happening in other countries.”He warned, “Our greatest concern is for the virus to spread to countries with weaker health systems that are ill prepared to deal with it.”The announcement …",2020,"Mahase, Elisabeth",BMJ,3003977029,#181,
,CZI,"Coronavirus latest: death toll passes 2,000",10.1136/bmj.m408,,,,"Updates on the respiratory illness that has infected tens of thousands of people. Scientists are concerned about a new virus that has infected tens of thousands of people and killed more than 2,000. The virus, which emerged in the Chinese city of Wuhan in December, is a coronavirus and belongs to the same family as the pathogen that causes severe acute respiratory syndrome, or SARS. It causes a respiratory illness called COVID-19, which can spread from person to person.",2020,Nature,Nature,3003977029,#1372,
,CZI,China coronavirus: Hong Kong health staff strike to demand border closure as city records first death,10.1136/bmj.m454,,,,"Hong Kong has reported its first death related to the novel coronavirus 2019-nCoV, only the second fatality reported outside mainland China, as healthcare workers in the city started unprecedented industrial action to put pressure on the government to close the border and avert an escalation in the number of infections.The 39 year old man, who had an underlying health condition, had travelled to Wuhan on 21 January. In late January, after his return to Hong Kong, he developed fever and myalgia. The Hong Kong Hospital Authority announced that he had died on 3 February. The news coincided with the second day of industrial action by members of the Hospital Authority Employees’ Alliance, a new labour union representing around 9000 of the 67 000 staff employed by the Hospital Authority, the statutory body that manages all of Hong Kong’s government hospitals.After a strike by 2700 non-essential staff on 2 February, the …",2020,"Parry, Jane",BMJ,3005117448,#221,
,CZI,"China coronavirus should be on “everybody’s agenda,” says vaccine expert",10.1136/bmj.m476,,,,"Novel coronavirus (2019-nCoV) should be on “everybody’s agenda,” says Seth Berkley, chief executive officer of Gavi, the Vaccine Alliance. He said that, while some responses may be “over-reaching,” what is currently known about the virus suggests that it should be treated seriously.Berkley, who spoke at a briefing in London on 4 February, told The BMJ that, although we “do not know enough right now to honestly answer the question [of over-reaction],” it is better to prepare now than to wait and see.“Does that mean that we should be having travel bans everywhere in the world and all of those other responses? I think there are certainly things that are over-reaching, but I think that the world is taking …",2020,"Mahase, Elisabeth",BMJ,,#295,
,CZI,Novel coronavirus: Australian GPs raise concerns about shortage of face masks,10.1136/bmj.m477,,,,"General practitioners in Australia have raised concerns over their safety and the safety of their teams because of the lack of protective equipment, including masks, which they said are needed to respond confidently to the novel coronavirus outbreak.Medical equipment suppliers have posted notices on their websites stating that they are no longer accepting orders of supplies such as masks, and GPs have told The BMJ that they are struggling to get hold of the supplies they need. The Royal Australian College of General Practitioners (RACGP) said that the recent bushfires had led to …",2020,"Mahase, Elisabeth",BMJ,3004966978,#296,
,CZI,"In Beijing, coronavirus 2019-nCoV has created a siege mentality",10.1136/bmj.m516,,32033967,,,2020,"Mowbray, Heather",BMJ,3005442318,#547,
,CZI,Coronavirus: doctor who faced backlash from police after warning of outbreak dies,10.1136/bmj.m528,,,,"Li Wenliang—a doctor from Wuhan, China, who said he was reprimanded by police for warning other doctors about novel coronavirus at the start of the outbreak—has died after being infected with 2019-nCoV.When the first cases of a pneumonia-like condition appeared in a local hospital, Li sent messages to his medical school alumni group on the Chinese messaging app WeChat, warning that, from the test results he had …",2020,"Mahase, Elisabeth",BMJ,3004702727,#388,
,CZI,"Coronavirus: global stocks of protective gear are depleted, with demand at “100 times” normal level, WHO warns",10.1136/bmj.m543,,,,"The demand for personal protective equipment such as masks and respirators is 100 times the normal level, and costs have skyrocketed to around 20 times their usual price, the World Health Organization has reported. WHO warned of “severe disruption” in the market for personal protective equipment and said that worldwide stocks were “now insufficient” to meet demand. The warning came from WHO’s director general, Tedros Adhanom Ghebreyesus, during his opening remarks at a briefing on 2019-nCoV on 7 February. He said that the situation had been “exacerbated by widespread, inappropriate use of personal protective equipment outside patient care.” This has led to “depleted stockpiles and backlogs of four to six months.” Last week The BMJ reported that GPs in Australia were finding it difficult to get the protective masks they needed because of shortages The demand for personal protective equipment such as masks and respirators is 100 times the normal level, and costs have skyrocketed to around 20 times their usual price, the World Health Organization has reported.WHO warned of “severe disruption” in the market for personal protective equipment and said that worldwide stocks were “now insufficient” to meet demand. The warning came from …",2020,"Mahase, Elisabeth",BMJ,,#599,
,CZI,Seven days in medicine: 5-11 Feb 2020,10.1136/bmj.m548,,,,"UK declares “serious and imminent threat to public health”The UK government declared that the “incidence or transmission of novel coronavirus constitutes a serious and imminent threat to public health.” The announcement on 10 February means that England’s health secretary, Matt Hancock, can enact regulations to ensure that people are “protected as far as possible from the transmission of the virus.” This includes designating Arrowe Park Hospital in Merseyside and Kents Hill Park in Milton Keynes as isolation facilities. As of 10 February eight people in the UK had tested positive for 2019-nCoV.More UK laboratories get diagnostic testingPublic Health England (PHE) announced that it was rolling out its novel coronavirus diagnostic test to 12 laboratories in England, Scotland, Wales, and Northern Ireland over the next few weeks, bringing the total facilities with testing capability to 13. This will increase the testing capacity in England from 100 to 1000 people a day. The test is performed on a sample from the nose, throat, and respiratory tract. A confirmatory test will continue to be conducted at PHE’s Colindale laboratories in north London. PHE is also working with the World Health Organization to test samples from countries that do not have testing facilities.Global stocks of protective gear are depletedThe demand for personal protective equipment such as masks and respirators is 100 times the normal level, and costs have skyrocketed to around 20 …",2020,,BMJ,2903965036,#806,
,CZI,Coronavirus: NHS staff get power to keep patients in isolation as UK declares “serious threat”,10.1136/bmj.m550,,,,"The UK government has declared that the incidence or transmission of the novel coronavirus 2019-nCoV constitutes a serious and imminent threat to public health. The announcement means that England’s health secretary, Matt Hancock, can enact regulations to ensure that the public is “protected as far as possible from the transmission of the virus.” This includes designating Arrowe Park Hospital, Merseyside, and the Kents Hill Park hotel and conference centre, Milton Keynes, as isolation facilities. It also means that NHS staff members have “strengthened powers” to keep patients in isolation if public health professionals believe there to be a “reasonable risk an individual may have the virus.” As at 10 February eight people in the UK had tested positive for 2019-nCoV. Globally, the virus has spread to 28 countries, with more than 40 000 cases and 900 deaths. The UK government has declared that the incidence or transmission of the novel coronavirus 2019-nCoV constitutes a serious and imminent threat to public health.The announcement means that England’s health secretary, Matt Hancock, can enact regulations to ensure that the public is “protected as far as possible from the transmission of the virus.” This includes designating Arrowe Park Hospital, Merseyside, and the Kents Hill Park hotel and conference centre, Milton Keynes, as isolation facilities.It also means that NHS staff members have “strengthened powers” to keep patients in isolation if public health professionals believe there to be a “reasonable risk an individual may have the virus.”As at 10 February eight people in the UK had tested positive for 2019-nCoV. Globally, the virus has spread to 28 countries, with more than 40 000 cases …",2020,"Mahase, Elisabeth",BMJ,,#600,
,CZI,"Coronavirus: online GP bookings should be stopped because of safety risks, warns BMA",10.1136/bmj.m611,,,,"General practices should be able to turn off their online booking systems in response to the covid-19 outbreak without fear of repercussions over breaching their contract, the BMA has told NHS England.Practices are contractually obliged to provide 25% of their appointments through online booking; as this system does not triage patients in the same way that a receptionist does, however, the BMA has warned that it could …",2020,"Mahase, Elisabeth",BMJ,3005624666,#876,
,CZI,Coronavirus: home testing pilot launched in London to cut hospital visits and ambulance use,10.1136/bmj.m621,,,,"People with suspected covid-19 in London are being tested in their homes as part of a pilot that was developed by doctors to stop unnecessary ambulance use and hospital visits.The community testing scheme started at the end of January at North West London NHS Trust and has now been implemented in three other trusts: University College London Hospital, St George’s University Hospital, and Guys and St Thomas’. More than 130 patients have been tested in two weeks.The home testing initiative was started by Laurence John from the infectious diseases department at Northwick Park Hospital. He told The BMJ that the need for community testing became clear after 25 London ambulances had to be taken out of …",2020,"Mahase, Elisabeth",BMJ,3006625193,#942,
,CZI,What did we learn from Tamiflu?,10.1136/bmj.m626,,,,"Ten years after questions were first raised over its effectiveness, Owen Dyer charts the fortunes of this blockbuster pill and finds that lack of evidence has not dented its successGovernments cannot calm earthquakes, bottle up volcanoes, or hold back tsunamis—they may not even be able to put out wildfires—but one disaster they do claim to have power over is a flu epidemic. Since the first pandemic scare of this century, H5N1 avian influenza in 2004 (see timeline, box 1), governments have been stockpiling the neuraminidase inhibitors zanamivir (Relenza) and especially oseltamivir (Tamiflu), in vast quantities.Box 1 Oseltamivir and pandemic flu preparedness—key events 2003—US adds oseltamivir to its strategic national stockpile2004—First outbreak of H5N1 avian flu in humans2005—UK announces it will stockpile 14 million doses of oseltamivir2006—Cochrane review concludes that oseltamivir reduces complications and symptoms in seasonal flu2009—H1N1 swine flu pandemic declared by WHO2009—The BMJ publishes critical Cochrane update review of oseltamivir2011—FOI request results in European Medicines Agency releasing 20 000 pages of oseltamivir data2013—GSK and Roche release trial data on zanamivir and oseltamivir2014—Cochrane review finds insufficient evidence that oseltamivir reduces lower respiratory complications or impedes transmission2016—Generic formulations of oseltamivir become available2017—WHO downgrades status of oseltamivir2020—Cochrane team member Thomas Jefferson sues Roche in US for wrongfully billing public health authorities for oseltamivir as a pandemic response drugRETURN TO TEXTThe UK, the US, and many other countries hold enough stocks of these antivirals to offer courses of treatment to a quarter of their population. The practice is almost ubiquitous in rich countries. Of 28 European states that have published a pandemic response plan, all but one (Poland) make oseltamivir the mainstay of their response until a vaccine can be developed.In the public mind, and the minds of politicians, the flu pandemic problem is one that has …",2020,"Dyer, Owen",BMJ,3001941086,#1315,
,CZI,Covid-19: a puzzle with many missing pieces,10.1136/bmj.m627,,,,"Better information on epidemiology, pathogenesis, and treatments are urgent prioritiesBy 15 February 2020, 51 800 cases of the novel coronavirus disease (formerly known as 2019-nCoV and renamed covid-19), including more than 1600 deaths, had been confirmed in China, mainly in Hubei province. A further 526 laboratory confirmed cases have been reported across 25 other countries.1 As is usual in the early phase of a disease outbreak, the alarm was raised as a result of the most severe cases, and the first reports describe severe pneumonia in patients admitted to hospital.2In a linked paper, Xu and colleagues (doi:10.1136/bmj.m606) report a case series of 62 patients (median age 41 years) admitted to hospital in the Zhejiang province with laboratory confirmed infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for covid-19.3 All the patients presented with respiratory symptoms, fever or flu-like illness, or both, and all had travelled to Wuhan or been in contact with a patient with confirmed covid-19 while staying in Wuhan. All but one had radiologically confirmed pneumonia, but only one patient was subsequently admitted to an intensive care unit …",2020,"Vetter, Pauline; Eckerle, Isabella; Kaiser, Laurent",BMJ,1976382352,#1267,
,CZI,Coronaviruses in animals and humans,10.1136/bmj.m634,,,,"Controlling outbreaks will require detailed knowledge of their biology and behaviourCoronaviruses have been around for many years and were first discovered in the 1960s. They include viruses contributing to the common cold (HCoV-229E) and a variety of animal and avian coronaviruses, such as infectious bronchitis virus (IBV), which infects poultry. Coronaviruses typically cause respiratory or gastrointestinal illness, but strains of IBV have been shown to target the oviduct in chickens, and others can cause severe kidney disease.Animal and avian coronaviruses can have high mortality rates among infected animals and illustrate the difficulties in developing vaccines. Similar to influenza viruses, despite many decades of research there is no vaccine that protects against all strains of IBV coronavirus. This is due in part to the continuously shifting diversity in the virus spike glycoprotein, a major immunogenic target and hence a good vaccine candidate for animal and human infections.During the mid-1990s these viruses were described as the backwater of virology, since none caused serious disease in humans. However, this changed in 2002-03 with …",2020,"Ng, Lisa F. P.; Hiscox, Julian A.",BMJ,2577028059,#1281,
,CZI,"Coronavirus covid-19 has killed more people than SARS and MERS combined, despite lower case fatality rate",10.1136/bmj.m641,,,,"The novel coronavirus that has so far spread from China to 26 countries around the world does not seem to be as “deadly as other coronaviruses including SARS and MERS,” the World Health Organization has said.At a briefing on 17 February WHO’s director general, Tedros Adhanom Ghebreyesus, said that more than 80% of patients with covid-19 have a “mild disease and will recover” and that it is fatal in 2% of reported cases. In comparison, the 2003 outbreak of severe acute respiratory syndrome (SARS) had a case fatality rate of around 10% (8098 cases and 774 deaths), while Middle East respiratory syndrome (MERS) killed 34% of people with the illness …",2020,"Mahase, Elisabeth",BMJ,3006642361,#1245,
,CZI,"Letter from China: covid-19 on the grapevine, on the internet, and in commerce",10.1136/bmj.m643,,,,"In medically murky times in China, people are turning to rumour, hope, and faith to protect themselves from the new coronavirus. In Beijing, Heather Mowbray is hearing all sorts of stories about how to stop the virus—but scientific evidence for the advice is woefully absentHere’s one example of the ideas floating around in China. Radio Free Asia reported that a Tibetan man named Tse was encouraging people to recite and forward a Buddhist prayer as a safeguard against the new coronavirus, covid-19. He was arrested for his efforts. Spreading rumours can land you in jail for seven years.Community imposed social isolation means that everyone has plenty of time to read the latest news and advice online. Children have web based schooling, and adults do their searches from the kitchen table. The news aggregator Jinri Toutiao has leapt to the top of the app download list in the past month. …",2020,"Mowbray, Heather",BMJ,3005550222,#1282,
,CZI,Coronavirus: Wales tests 90% of suspected patients in their own home,10.1136/bmj.m698,,,,"Wales has managed to test 90% of people suspected of being infected with novel coronavirus in their own homes, after implementing community testing for covid-19.Vaughan Gething, minister for health and social services in Wales, credited the NHS with making the process “as convenient as possible for people whilst also protecting our ambulance and hospital resources for those who need it most.”More than 100 people had been tested in Wales as of 13 February, with no positive cases. Around the UK, nine …",2020,"Mahase, Elisabeth",BMJ,1968634965,#1376,
,CZI,Rules on isolation rooms for suspected covid-19 cases in GP surgeries to be relaxed,10.1136/bmj.m707,,32086235,,,2020,"Kmietowicz, Zosia",BMJ,2171042902,#1604,
,CZI,Covid-19: surge in cases in Italy and South Korea makes pandemic look more likely,10.1136/bmj.m751,,32098875,,,2020,"Day, Michael",BMJ,2317219333,#2311,
,CZI,Covid-19: Italy confirms 11 deaths as cases spread from north,10.1136/bmj.m757,,32102793,,,2020,"Day, M.",BMJ (Clinical research ed.),2742206604,#2785,
,CZI,Healthcare information for all,10.1136/bmj.m759,,,,"Together, we can stop people dying from a lack of timely accurate healthcare information The World Medical Association (WMA) has unanimously approved a statement on healthcare information for all, proposed by the British Medical Association.1 The statement notes that lack of access to timely, current, evidence based healthcare information continues to be a major contributor to morbidity and mortality, especially in low and middle income countries, and calls on doctors worldwide to support initiatives to improve access for health professionals, patients, and the public. The BMJ hosted a conference on this issue in 19942 and cofounded Hinari in 2001, a partnership between publishers and the World Health Organization to improve the availability of e-journals and e-books in low and middle income countries.3 In 2004 we coauthored a paper in the Lancet describing the global healthcare information system and its interdependent parts.4 We called for a global campaign to support communication, understanding, and advocacy among all stakeholders. These include researchers, journal publishers, systematic reviewers, guideline developers, publishers of secondary materials (from textbooks to radio shows), those who guide and provide access (from search engines to librarians), and all who share the vision of a world where everyone has access to the information they need to protect their own and others’ health. Healthcare Information For All (HIFA) now has 20 000 members …",2020,"Pakenham-Walsh, Neil; Godlee, Fiona",BMJ,2057196240,#4937,
,CZI,Covid-19: a digital epidemic,10.1136/bmj.m764,,,,"The covid-19 epidemic is not only viral—it is also digital.1Information spread through social and traditional media, as well as through governmental or health agencies, has reached …",2020,"Chiolero, Arnaud",BMJ,3006419170,#3197,
,CZI,"Covid-19: Trump says risk to Americans is ""very low""",10.1136/bmj.m793,,32107254,,,2020,"Tanne, J. H.",BMJ (Clinical research ed.),2170383333,#2957,
,CZI,"Covid-19: preparedness, decentralisation, and the hunt for patient zero",10.1136/bmj.m799,,32111645,,,2020,"Carinci, F.",BMJ (Clinical research ed.),3005981248,#2748,
,CZI,Coronavirus disease 2019 (covid-19): a guide for UK GPs,10.1136/bmj.m800,,,,"What you need to knowConsider covid-19 infection in anyone with cough, fever, or breathlessness who has had contact with someone with covid-19, or has returned from a high risk area in the 14 days before the onset of symptomsEvery effort should be made to avoid in-person assessment of patients with possible covid-19 in primary careGP surgeries should plan ahead and develop clear protocols for managing possible cases, including isolation procedures, personal protective equipment, seeking specialist advice, and decontaminationIf covid-19 infection is suspected in someone attending the practice, isolate the patient in a room (away from other patients and staff), close the door, and ask the patient to call NHS 111The guidance may change so it is essential to look at the latest guidance online (box 1)The UK recorded its first confirmed case of acute respiratory infection due to coronavirus disease 2019 (covid-19) on 31 January 2020 and responded by quarantining at-risk individuals to contain the spread of infection. Executive agencies Public Health England (PHE)1 and Health Protection Scotland (HPS) have since published guidance to healthcare providers on managing patients suspected to have the disease.Guidance for the public and health professionals varies internationally, depending partly on risk levels and healthcare systems, and is being regularly updated.This article offers a practical guide for GPs and others working in UK primary care on when to suspect covid-19 and how to respond. It is based on current UK guidance at the time of publication. We recommend readers consult the latest guidance (box 1).Box 1 Essential resourcescovid-19: latest case definition, investigation, and initial clinical management of possible cases:https://www.gov.uk/government/publications/wuhan-novel-coronavirus-initial-investigation-of-possible-cases/investigation-and-initial-clinical-management-of-possible-cases-of-wuhan-novel-coronavirus-wn-cov-infectionCoronavirus: latest information and advice including updated list of high risk countries:https://www.gov.uk/guidance/wuhan-novel-coronavirus-information-for-the-publicGuidance on isolation of healthcare workers:https://www.gov.uk/government/publications/novel-coronavirus-2019-ncov-guidance-for-healthcare-providers-with-staff-who-have-travelled-to-china/guidance-for-healthcare-providers-healthcare-workers-who-have-travelled-to-chinaFind your local Health Protection Team in England:https://www.gov.uk/health-protection-teamcovid-19: interim guidance … RETURN TO TEXT",2020,"Razai, Mohammad S.; Doerholt, Katja; Ladhani, Shamez; Oakeshott, Pippa",BMJ,2604381070,#4464,
,CZI,"Covid-19: school closures and bans on mass gatherings will need to be considered, says England's CMO",10.1136/bmj.m806,,32111656,,,2020,"Moberly, T.",BMJ (Clinical research ed.),2738470870,#2902,
,CZI,Preventing a covid-19 pandemic,10.1136/bmj.m810,,32111649,,,2020,"Watkins, J.",BMJ (Clinical research ed.),3005847234,#2972,
,CZI,Sixty seconds on . . . beards,10.1136/bmj.m811,,,,"Now calm down, we’re not about to start dolling out fashion tips for your facial fuzz. We’re talking about how having a hairy face could stop protective face masks from fitting properly.It can do. Derek Sandeman, the medical director of the University Hospital Southampton NHS Foundation Trust, has written to his clinical staff asking anyone working in high risk …",2020,"Rimmer, Abi",BMJ,3004180009,#3316,
,CZI,"Covid-19: retired doctors could be asked to return to work, says Hancock",10.1136/bmj.m831,,32122881,,,2020,"Mahase, Elisabeth",BMJ,2330696540,#3334,
,CZI,"Covid-19: US health department staff sent to meet citizens returning from China weren't protected, claims whistleblower",10.1136/bmj.m833,,32122875,,,2020,"Dyer, Owen",BMJ,2612454967,#3410,
,CZI,Covid-19: UK could delay non-urgent care and call doctors back from leave and retirement,10.1136/bmj.m854,,,,"Healthcare staff on leave and those who have retired could be called “back to duty,” and non-urgent care could be delayed, as doctors are forced to prioritise dealing with covid-19, the UK government’s action plan lays out.The government will also implement a “distribution strategy for the UK’s stockpiles of key medicines and equipment (e.g. protective clothing),” the document said.However, the plan did not include details of how or when these measures would be …",2020,"Mahase, Elisabeth",BMJ,2151773763,#3336,
,CZI,Prepare for a pandemic,10.1136/bmj.m864,,,,"A covid-19 pandemic is highly likely, warns our editorialist, the epidemiologist John Watkins (doi:10.1136/bmj.m810), and we need to plan now how to reconfigure care services to cope with the looming escalation in demand. “We should plan on the assumption that most of the population may contract the virus with few or no long term effects,” he writes, “while harnessing vital secondary healthcare resources to treat the small percentage of people who become seriously ill.”As at Tuesday 3 March the UK had confirmed 51 cases of infection (doi: …",2020,"Hurley, Richard",BMJ,2091233622,#4551,
,CZI,"Covid-19: hoarding and misuse of protective gear is jeopardising the response, WHO warns",10.1136/bmj.m869,,,,"Nearly 90 million face masks are required every month to protect health staff as they tackle covid-19, the World Health Organization has estimated, as it warned that current supplies were “rapidly depleting.”The ability of countries to respond to the outbreak is being compromised by the “severe and increasing disruption to the global supply of personal protective equipment—caused by rising demand, hoarding, and misuse,” said WHO’s director general, Tedros Adhanom Ghebreyesus.Speaking at the daily press briefing on 3 March, he warned …",2020,"Mahase, Elisabeth",BMJ,3005244019,#3826,
,CZI,"Covid-19: 90% of cases will hit NHS over nine week period, chief medical officer warns",10.1136/bmj.m918,,,,"Nearly all covid-19 cases will hit the NHS in a “heavily concentrated” burst, with 50% of cases predicted to happen over a three week period and 90% over nine weeks, says the chief medical officer for England, Chris Whitty.Speaking to the Health and Social Care Committee on 5 March, Whitty said that the NHS would be put under huge pressure and would have to push some routine care to before or after the expected peak of cases.Adding more detail to the government’s suggestion1 that retired doctors could be called “back to duty,” he said that doctors who had retired in the past two to three years would be considered and that he was “confident” that many would …",2020,"Mahase, Elisabeth",BMJ,2197453954,#4499,
,CZI,Covid-19: are we getting the communications right?,10.1136/bmj.m919,,32144115,,,2020,"Cowper, A.",BMJ (Clinical research ed.),3006304371,#5160,
,CZI,Covid-19: GP surgeries close for two weeks after staff test positive,10.1136/bmj.m936,,32144111,,,2020,"Iacobucci, G.",BMJ (Clinical research ed.),2048387827,#4739,
,CZI,Trump claims public health warnings on covid-19 are a conspiracy against him,10.1136/bmj.m941,,32144176,,,2020,"Dyer, O.",BMJ (Clinical research ed.),3005995896,#5189,
,CZI,"Covid-19: UK records first death, as world's cases exceed 100 000",10.1136/bmj.m943,,32144096,,,2020,"Mahase, E.",BMJ (Clinical research ed.),2332386010,#4882,
,CZI,Diarrhoea may be underestimated: a missing link in 2019 novel coronavirus,10.1136/gutjnl-2020-320832,,32102928,,,2020,"Liang, W.; Feng, Z.; Rao, S.; Xiao, C.; Xue, X.; Lin, Z.; Zhang, Q.; Qi, W.",Gut,3005757890,#2880,
,CZI,SARS-CoV-2 induced diarrhoea as onset symptom in patient with COVID-19,10.1136/gutjnl-2020-320891,,32139552,,,2020,"Song, Y.; Liu, P.; Shi, X. L.; Chu, Y. L.; Zhang, J.; Xia, J.; Gao, X. Z.; Qu, T.; Wang, M. Y.",Gut,2093565992,#5236,
,CZI,Where did SARS-CoV-2 come from?,10.1136/vr.m740,,32108071,,,2020,"Zhai, S. L.; Wei, W. K.; Lv, D. H.; Xu, Z. H.; Chen, Q. L.; Sun, M. F.; Li, F.; Wang, D.",The Veterinary record,2606000111,#3017,
,CZI,Advantages and challenges of metagenomic next-generation sequencing (mNGS) in the detection of 2019 novel coronavirus,10.1146/annurev-pathmechdis-012418-012751,,,,"As one of the two methods for 2019 novel coronavirus (2019-nCoV), gene sequencing is different from quantitative real-time PCR (RT-PCR) in detection principles. Therefore, gene sequencing has its own pros and cons in clinical application. Currently, metagenomic next-generation sequencing (mNGS) is the most commonly used technology in clinical application. Due to its broad coverage of all types of pathogens, mNGS demonstrates incomparable advantage in rapid identification of novel pathogens such as 2019-nCoV. In addition, it can simultaneously identify other pathogens except 2019-nCoV and mixed infections. On the other hand, however, due to the complexity of mNGS and long detection time, it is unlikely to achieve the purpose of wide-range and rapid diagnosis of 2019 n-CoV. Therefore, mNGS can complement RT-PCR to achieve best clinical application.",2020,"TAO, Yue; FU, Qihua; MO, Xi",Chinese Journal of Laboratory Medicine,2898604559,#2380,
,CZI,CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV),10.1148/radiol.2020200230,,32017661,,"In this retrospective case series, chest CT scans of 21 symptomatic patients from China infected with the 2019 Novel Coronavirus (2019-nCoV) were reviewed with emphasis on identifying and characterizing the most common findings. Typical CT findings included bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, sometimes with a rounded morphology and a peripheral lung distribution. Notably, lung cavitation, discrete pulmonary nodules, pleural effusions, and lymphadenopathy were absent. Follow-up imaging in a subset of patients during the study time window often demonstrated mild or moderate progression of disease as manifested by increasing extent and density of lung opacities.",2020,"Chung, Michael; Bernheim, Adam; Mei, Xueyan; Zhang, Ning; Huang, Mingqian; Zeng, Xianjian; Cui, Jiufa; Xu, Wenjian; Yang, Yang; Fayad, Zahi; Jacobi, Adam; Li, Kunwei; Li, Shaolin; Shan, Hong",Radiology,3004906315,#333,
,CZI,CT Imaging of the 2019 Novel Coronavirus (2019-nCoV) Pneumonia,10.1148/radiol.2020200236,,32003646,,,2020,"Lei, J.; Li, J.; Li, X.; Qi, X.",Radiology,3003901880,#141,
,CZI,2019 novel coronavirus (2019-nCoV) and 2019-nCoV pneumonia,10.1148/radiol.2020200236,,,,"In the middle of December in 2019, a pneumonia outbreak caused by a new coronavirus, 2019 novel coronavirus (2019-nCoV), emerged in the populations in Wuhan city of China. The epidemic spreads rapidly and has been disseminated throughout the country and to 13 other counties in Asia, Europe, Oceania and North America. To accurately and deeply understand the biological characteristics, epidemiological features and pathogenicity of 2019-nCoV and related immunological characteristics, microbiological examinations and public protection measure, this study reviewed 2019-nCoV and 2019-nCoV pneumonia based on the newest relevant literatures and the newest version of National Diagnosis and Treatment Scheme of 2019-nCoV pneumonia.",2020,"YAN, Jie; LI, Mingyuan; SUN, Aihua; PENG, Yihong",Chinese Journal of Microbiology and Immunology,3003901880,#2096,
,CZI,"Chest CT Findings in 2019 Novel Coronavirus (2019-nCoV) Infections from Wuhan, China: Key Points for the Radiologist",10.1148/radiol.2020200241,,32017662,,,2020,"Kanne, Jeffrey P.",Radiology,3005272159,#316,
,CZI,2019 Novel Coronavirus (2019-nCoV) Pneumonia,10.1148/radiol.2020200257,,32013795,,,2020,"Liu, Peng; Tan, Xian-Zheng",Radiology,3004826915,#304,
,CZI,"Evolution of CT Manifestations in a Patient Recovered from 2019 Novel Coronavirus (2019-nCoV) Pneumonia in Wuhan, China",10.1148/radiol.2020200269,,32032497,,,2020,"Shi, Heshui; Han, Xiaoyu; Zheng, Chuansheng",Radiology,3004511262,#494,
,CZI,CT features of 2019-novel coronovirus pneumonia: SARS and MERS literature review and analysis of CT features of two confirmed 2019-novel coronavirus pneumonia cases,10.1148/radiol.2020200269,,,,"Objective To analyze the CT manifestations of the 2019 novel coronavirus pneumonia (NCP) combined with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) literature review, and to summarize the characteristics of CT imaging, so as to improve the ability of rapid and accurate diagnosis. Methods CT manifestations of two confirmed cases of NCP were reported, meanwhile the literatures on SARS and MERS imaging performance were reviewed and summarized. Results The two cases of NCP were both in acute stage, the CT imaging showed multiple and scattered ground-glass opacity (GGO) in both lungs, which is similar to the CT performance of SARS and MERS in acute stage. Conclusions The CT features of 2019 novel coronavirus pneumonia are similar to SARS and MERS. It has certain characteristics and changes rapidly with the course of the disease. In the acute stage, GGO and paving stone sign were the main manifestations. In the acute phase, GGO and crazy paving are the main manifestations. In the progress stage, the interlobular septal thickening and consolidation appeared. During the absorption period, the lesions disappeared or fibrosis was left behind, with lung structure distortion and bronchiectasis. Lymphadenopathy and hydrothorax were rare.",2020,"YANG, Changwei; FAN, Chenghui; CHENG, Ailan; LIU, Jing; ZHU, Chongwen; HU, Bo; WANG, Rongfang; QU, Lihong; CHU, Shuguang",Chinese Critical Care Medicine,3004511262,#2094,
,CZI,Emerging Coronavirus 2019-nCoV Pneumonia,10.1148/radiol.2020200274,,32027573,,"Background The chest CT findings of patients with coronavirus 2019-nCoV pneumonia have not previously been described in detail. Purpose To investigate the clinical, laboratory, and imaging findings of emerging coronavirus 2019-nCoV pneumonia in humans. Materials and Methods Fifty-one patients (25 men and 26 women, 16-76 years old) with 2019-nCoV pneumonia confirmed with the positive new coronavirus nucleic acid antibody underwent thin-section CT. The imaging findings, clinical and laboratory data were evaluated. Results Fifty of 51 patients (98%) had a history of the endemic center Wuhan contact. Fever (49/51, 96%) and cough (24/51, 47%) were the most common symptoms. Most patients had a normal white blood cell count (37/51, 73%), neutrophil count (44/51, 86.3%) and normal (17/51, 35.3%) or reduced (33/51, 64.7%) lymphocyte count. CT images showed pure ground grass opacity (GGO) in 39/51 (77%) patients, GGO with reticular and/or interlobular septal thickening in 38/51 (75%) patients. GGO with consolidation was present in 30/51 (59%) and pure consolidation in 28/51 (55%) patients. 44/51 (86%) patients had bilateral lung involvement, while 41/51 (80%) involved the posterior part of the lungs and 44/51 (86%) were peripheral. There were more consolidated lung lesions in patients 5 or more days from disease onset to CT scan versus 4 or fewer days (431/712 lesions vs. 129/612 lesions, p < 0.001). Patients more than 50 years old had more consolidated lung lesions than those 50 years or younger (212/470 vs. 198/854, p < 0.001). Follow up CT in 13 patients showed improvement in 7 (54%) patients and progression in 4 (31%) patients. Conclusions Patients with fever and/or cough and with conspicuous ground grass opacity lesions in the peripheral and posterior lungs on CT images combined with normal or decreased white blood cells and a history of epidemic exposure are highly suspected of 2019-nCoV pneumonia.",2020,"Song, Fengxiang; Shi, Nannan; Shan, Fei; Zhang, Zhiyong; Shen, Jie; Lu, Hongzhou; Ling, Yun; Jiang, Yebin; Shi, Yuxin",Radiology,3004668429,#465,
,CZI,CT Manifestations of Two Cases of 2019 Novel Coronavirus (2019-nCoV) Pneumonia,10.1148/radiol.2020200280,,32031481,,,2020,"Fang, Yicheng; Zhang, Huangqi; Xu, Yunyu; Xie, Jicheng; Pang, Peipei; Ji, Wenbin",Radiology,3004802901,#495,
,CZI,Pre- and Posttreatment Chest CT Findings: 2019 Novel Coronavirus (2019-nCoV) Pneumonia,10.1148/radiol.2020200323,,32049602,,,2020,"Duan, Ya-Ni; Qin, Jie",Radiology,3006328792,#780,
,CZI,Use of Chest CT in Combination with Negative RT-PCR Assay for the 2019 Novel Coronavirus but High Clinical Suspicion,10.1148/radiol.2020200330,,32049600,,,2020,"Huang, Peikai; Liu, Tianzhu; Huang, Lesheng; Liu, Hailong; Lei, Ming; Xu, Wangdong; Hu, Xiaolu; Chen, Jun; Liu, Bo",Radiology,3005656138,#769,
,CZI,Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing,10.1148/radiol.2020200343,,32049601,,"Some patients with positive chest CT findings may present with negative results of real time reverse-transcription-polymerase chain- reaction (RT-PCR) for 2019 novel coronavirus (2019-nCoV). In this report, we present chest CT findings from five patients with 2019-nCoV infection who had initial negative RT-PCR results. All five patients had typical imaging findings, including ground-glass opacity (GGO) (5 patients) and/or mixed GGO and mixed consolidation (2 patients). After isolation for presumed 2019-nCoV pneumonia, all patients were eventually confirmed with 2019-nCoV infection by repeated swab tests. A combination of repeated swab tests and CT scanning may be helpful when for individuals with high clinical suspicion of nCoV infection but negative RT-PCR screening.",2020,"Xie, Xingzhi; Zhong, Zheng; Zhao, Wei; Zheng, Chao; Wang, Fei; Liu, Jun",Radiology,3006110666,#715,
,CZI,Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus (COVID-19) Pneumonia,10.1148/radiol.2020200370,,32053470,,"Background Chest CT is used to assess the severity of lung involvement in COVID-19 pneumonia. Purpose To determine the change in chest CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. Materials and Methods This retrospective review included patients with RT-PCR confirmed COVID-19 infection presenting between 12 January 2020 to 6 February 2020. Patients with severe respiratory distress and/ or oxygen requirement at any time during the disease course were excluded. Repeat Chest CT was obtained at approximately 4 day intervals. The total CT score was the sum of lung involvement (5 lobes, score 1-5 for each lobe, range, 0 none, 25 maximum) was determined. Results Twenty one patients (6 males and 15 females, age 25-63 years) with confirmed COVID-19 pneumonia were evaluated. These patients under went a total of 82 pulmonary CT scans with a mean interval of 4±1 days (range: 1-8 days). All patients were discharged after a mean hospitalized period of 17±4 days (range: 11-26 days). Maximum lung involved peaked at approximately 10 days (with the calculated total CT score of 6) from the onset of initial symptoms (R2=0.25), p<0.001). Based on quartiles of patients from day 0 to day 26 involvement, 4 stages of lung CT were defined: Stage 1 (0-4 days): ground glass opacities (GGO) in 18/24 (75%) patients with the total CT score of 2±2; (2)Stage-2 (5-8d days): increased crazy-paving pattern 9/17 patients (53%) with a increase in total CT score (6±4, p=0.002); (3) Stage-3 (9-13days): consolidation 19/21 (91%) patients with the peak of total CT score (7±4); (4) Stage-4 (≥14 days): gradual resolution of consolidation 15/20 (75%) patients with a decreased total CT score (6±4) without crazy-paving pattern. Conclusion In patients recovering from COVID-19 pneumonia (without severe respiratory distress during the disease course), lung abnormalities on chest CT showed greatest severity approximately 10 days after initial onset of symptoms.",2020,"Pan, Feng; Ye, Tianhe; Sun, Peng; Gui, Shan; Liang, Bo; Li, Lingli; Zheng, Dandan; Wang, Jiazheng; Hesketh, Richard L.; Yang, Lian; Zheng, Chuansheng",Radiology,3006643024,#823,
,CZI,Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR,10.1148/radiol.2020200432,,32073353,,,2020,"Fang, Yicheng; Zhang, Huangqi; Xie, Jicheng; Lin, Minjie; Ying, Lingjun; Pang, Peipei; Ji, Wenbin",Radiology,2164629904,#1311,
,CZI,Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection,10.1148/radiol.2020200463,,32077789,,"In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed for common CT findings in relationship to the time between symptom onset and the initial CT scan (i.e. early, 0-2 days (36 patients), intermediate 3-5 days (33 patients), late 6-12 days (25 patients)). The hallmarks of COVID-19 infection on imaging were bilateral and peripheral ground-glass and consolidative pulmonary opacities. Notably, 20/36 (56%) of early patients had a normal CT. With a longer time after the onset of symptoms, CT findings were more frequent, including consolidation, bilateral and peripheral disease, greater total lung involvement, linear opacities, ""crazy-paving"" pattern and the ""reverse halo"" sign. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%).",2020,"Bernheim, Adam; Mei, Xueyan; Huang, Mingqian; Yang, Yang; Fayad, Zahi A.; Zhang, Ning; Diao, Kaiyue; Lin, Bin; Zhu, Xiqi; Li, Kunwei; Li, Shaolin; Shan, Hong; Jacobi, Adam; Chung, Michael",Radiology,2055651857,#1690,
,CZI,Coronavirus Disease 2019 (COVID-19): A Perspective from China,10.1148/radiol.2020200490,,32083985,,"In December 2019, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurred in Wuhan, Hubei Province, China and spread across China and beyond. On February 12, 2020, WHO officially named the disease caused by the novel coronavirus as Coronavirus Disease 2019 (COVID-19). Since most COVID-19 infected patients were diagnosed with pneumonia and characteristic CT imaging patterns, radiological examinations have become vital in early diagnosis and assessment of disease course. To date, CT findings have been recommended as major evidence for clinical diagnosis of COVID-19 in Hubei, China. This review focuses on the etiology, epidemiology, and clinical symptoms of COVID-19, while highlighting the role of chest CT in prevention and disease control. A full translation of this article in Chinese is available.",2020,"Zu, Zi Yue; Jiang, Meng Di; Xu, Peng Peng; Chen, Wen; Ni, Qian Qian; Lu, Guang Ming; Zhang, Long Jiang",Radiology,2604381070,#1419,
,CZI,Essentials for Radiologists on COVID-19: An Update-Radiology Scientific Expert Panel,10.1148/radiol.2020200527,,32105562,,,2020,"Kanne, J. P.; Little, B. P.; Chung, J. H.; Elicker, B. M.; Ketai, L. H.",Radiology,2800024516,#2856,
,CZI,Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases,10.1148/radiol.2020200642,,32101510,,"Background Chest CT is used for diagnosis of 2019 novel coronavirus disease (COVID-19), as an important complement to the reverse-transcription polymerase chain reaction (RT-PCR) tests. Purpose To investigate the diagnostic value and consistency of chest CT as compared with comparison to RT-PCR assay in COVID-19. Methods From January 6 to February 6, 2020, 1014 patients in Wuhan, China who underwent both chest CT and RT-PCR tests were included. With RT-PCR as reference standard, the performance of chest CT in diagnosing COVID-19 was assessed. Besides, for patients with multiple RT-PCR assays, the dynamic conversion of RT-PCR results (negative to positive, positive to negative, respectively) was analyzed as compared with serial chest CT scans for those with time-interval of 4 days or more. Results Of 1014 patients, 59% (601/1014) had positive RT-PCR results, and 88% (888/1014) had positive chest CT scans. The sensitivity of chest CT in suggesting COVID-19 was 97% (95%CI, 95-98%, 580/601 patients) based on positive RT-PCR results. In patients with negative RT-PCR results, 75% (308/413) had positive chest CT findings; of 308, 48% were considered as highly likely cases, with 33% as probable cases. By analysis of serial RT-PCR assays and CT scans, the mean interval time between the initial negative to positive RT-PCR results was 5.1 ± 1.5 days; the initial positive to subsequent negative RT-PCR result was 6.9 ± 2.3 days). 60% to 93% of cases had initial positive CT consistent with COVID-19 prior (or parallel) to the initial positive RT-PCR results. 42% (24/57) cases showed improvement in follow-up chest CT scans before the RT-PCR results turning negative. Conclusion Chest CT has a high sensitivity for diagnosis of COVID-19. Chest CT may be considered as a primary tool for the current COVID-19 detection in epidemic areas.",2020,"Ai, Tao; Yang, Zhenlu; Hou, Hongyan; Zhan, Chenao; Chen, Chong; Lv, Wenzhi; Tao, Qian; Sun, Ziyong; Xia, Liming",Radiology,3006110666,#2449,
,CZI,Helping the Radiologist: The Role of Scientific Journals to Help Prevent the Spread of COVID-19,10.1148/radiol.2020200661,,32125934,,,2020,"Li, Xiaohu; Qian, Yinfeng; Liu, Bin; Yu, Yongqiang",Radiology,230077627,#3358,
,CZI,Patients with RT-PCR Confirmed COVID-19 and Normal Chest CT,10.1148/radiol.2020200702,,32142398,,,2020,"Yang, W.; Yan, F.",Radiology,2894979147,#5367,
,CZI,FDG PET/CT of COVID-19,10.1148/radiol.2020200770,,32142399,,,2020,"Zou, S.; Zhu, X.",Radiology,2809328670,#5541,
,CZI,New coronavirus pneumonia and outbreak epidemic virus and eye disease,10.1155/2015/769121,,,,"Since the outbreak of the new coronavirus pneumonia (NCP) in Wuhan City, China, the main transmission mode as well as the diagnosis and treatment of NCP have become a focus of research in China and World Health Organizations. Understanding the mode of infection, transmission and biological behavior of the novel coronavirus (2019-nCoV) is undoubtedly a key of cutting off the spread and prevention of the disease which doctors are fearing to be a worldwide epidemic. In February 2019, Lancet published a correspondence paper, which reviewed a case of NCP patient who first started with conjunctivitis, and raised the issue that the transmission of 2019-nCoV through the ocular surface must not be ignored, causing widespread concern. However, due to a lack of clinical observation data and laboratory research at present, the relationship between NCP pathogen infection and ocular surface infection is not completely clear. So far, there have been many studies and reports on the observation of large-scale epidemic virus infections and eye diseases. This article reviews the eye performance of various types of epidemic virus infections and provides a reference for NCP prevention and control.",2020,"YIN, Shengjie; ZHANG, Mingzhi",Chinese Journal of Experimental Ophthalmology,2084228609,#2081,
,CZI,The treatment proposal for the patients with breast diseases in the central epidemic area of 2019 coronavirus disease,10.1158/1078-0432.CCR-10-2962,,32096395,,"Currently, the epidemic of 2019 coronavirus disease (COVID-19) is still ongoing. The characteristics including high contagiousness, herd susceptibility and clinical phenotype diversity, made a serious influence on people’s daily life and rountine therapy for other diseases. Breast dieases are clinical common diseases. In the central epidemic area of COVID-19, Hubei province, especially Wuhan, the clinical specialists of breast diseases should consider all of the following factors comprehensively: the prevention of COVID-19, the diagnosis and treatment of breast diseases and the accessibility of medical resources. Besides, we should select the appropriate therapy and optimize treatment process so as to prevent the propagation and cross infection of COVID-19 as well as manage the breast diseases without delay. Therefore, we carried out some management proposals of the patients with breast diseases in the central epidemic area during the epidemic of COVID-19 on the basis of conventional treatment guidelines and clinical experiences. The suggestions and corrections from colleagues will be welcomed.",2020,"ZHAO, Lu; ZHANG, Lin; LIU, Jinwen; YANG, Zhifang; SHEN, Wenzhuang; LI, Xingrui",Chinese Journal of Surgery,2130735457,#1890,
,CZI,Outbreak of COVID-19 - an urgent need for good science to silence our fears?,10.11622/smedj.2020018,,32052064,,,2020,"Lum, Lionel Hw; Tambyah, Paul A.",Singapore Med J,3005969859,#818,
,CZI,The recommendation for management of the bereavements among the family members died with novel coronavirus pneumonia,10.1164/ajrccm-conference.2012.185.1_MeetingAbstracts.A4259,,,,"The death of a family member died with the novel coronavirus pneumonia is a special traumatic stress to the other family members and they will bear unbelievable distress and dramatic sorrow. The grief responses can be divided into normal grief responses and abnormal grief responses. The latter are much stronger, more severe, last longer and the responses can be delayed or inhibited or distorted. The management of abnormal grief responses includes counseling, supportive group, psychotherapy and medications.",2020,"JI, Jianlin",Chinese Journal of Behavioral Medicine and Brain Science,2324157363,#2248,
,CZI,Understanding the Influence Factors in Viral Nucleic Acid Test of 2019 novel Coronavirus (2019-nCoV),10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a5218,,,,"At present, the prevention and control of new coronavirus has entered a critical period. However, the use of quantitative real-time PCR (qRT-PCR) assays for the detection of viral nucleic acid, as a crucial diagnostic approach, has been doubted in clinical practice. Herein, we have reviewed the current status of epidemic prevention and control, latest development of detection technologies, disease characteristics, clinical sampling and transport. We have also discussed the factors that may affect the performance of viral nucleic acid detection, and suggested some effective methods to improve the detection performance of the assays.",2020,"XI, Mo; WEI, Qin; QIHUA, Fu; MING, Guan",Chinese Journal of Laboratory Medicine,2970372942,#2117,
,CZI,Novel Wuhan (2019-nCoV) Coronavirus,10.1164/rccm.2014P7,,32004066,,,2020,"Carlos, W. G.; Dela Cruz, C. S.; Cao, B.; Pasnick, S.; Jamil, S.",American journal of respiratory and critical care medicine,3003347489,#107,
,CZI,Visualising the expansion and spread of coronavirus disease 2019 by cartograms,10.1177/0308518X20910162,,,,"Coronavirus disease 2019 (COVID-19) has emerged as a growing focus of global attention and a critical factor in public-health decision making. Towards fighting the COVID-19 outbreak, countries worldwide and international organisations have taken various actions, including promoting the transparency of and public access to disease data. In such public communications, maps have played an important role in that a map is worth a thousand words. Most of these have taken the form of a choropleth map. Here, we propose employing cartograms to visualise both the expansion and spread of COVID-19. We designed a combination of six circular cartograms containing the data of confirmed cases every 48 hours from 24 January to 3 February 2020. Such a design conveys both spatial and temporal information more intuitively and efficiently, so it can be expected to facilitate better public participation in the fight against COVID-19.",2020,"Gao, Peichao; Zhang, Hong; Wu, Zhiwei; Wang, Jicheng",Environment and Planning A: Economy and Space,3006007867,#2287,
,CZI,CT Imaging and Differential Diagnosis of COVID-19,10.1177/0846537120913033,,,,"Since the beginning of 2020, coronavirus disease 2019 (COVID-19) has spread throughout China. This study explains the findings from lung computed tomography images of some patients with COVID-19 treated in this medical institution and discusses the difference between COVID-19 and other lung diseases.",2020,"Dai, Wei-cai; Zhang, Han-wen; Yu, Juan; Xu, Hua-jian; Chen, Huan; Luo, Si-ping; Zhang, Hong; Liang, Li-hong; Wu, Xiao-liu; Lei, Yi; Lin, Fan",Canadian Association of Radiologists Journal,2605750182,#4047,
,CZI,COVID-19: What Can We Learn From Stories From the Trenches?,10.1177/0846537120913497,,,,"A few reports have been published recently highlighting the role of chest computed tomography (CT) in diagnosis of COVID-19.2-4 Chest CT demonstrates a high sensitivity in patients with COVID-19. The CT imaging findings in COVID-19 are similar to features of other viral pneumonias and familiar to imagers.2-4 The speed of acquisition of CT and timely reporting by radiologists will help our ED colleagues to make a diagnosis of COVID-19 within minutes, not hours or days. Nevertheless, this outbreak raises important clinical questions relevant to radiological community.",2020,"Patlas, Michael N.",Canadian Association of Radiologists Journal,2248885652,#3889,
,CZI,The 2019-nCoV epidemic control strategies and future challenges of building healthy smart cities,10.1177/1420326X20910408,,,,"reported and confirmed on 31 December 2019, in Wuhan, Hubei Province, China, which is one of China’s largest cities and a major domestic transport hub (located in the central part of China, as shown in Figure 1).1 The epidemic is attracting worldwide concern due to its rapid spread and transmission rate between humans. On 30 January 2020, the International Health Regulations, Emergency Committee of the World Health Organization (WHO) declared the outbreak – a ‘public health emergency of international concern’.2 On 8 February 2020 (24:00 GMT?+?8), there were 37,198 confirmed infections in China (including 811 deaths with a death ratio of 2.1%; and 6188 patients were confirmed in serious condition and 28,942 suspected cases).3 The COVID 19 infections were also reported in 26 other countries on 7 February 2020, including Canada, the USA, Australia, India, Sri-Lanka, Cambodia, Thailand, Vietnam, Malaysia, Singapore, Taiwan, the Republic of Korea, Sri Lanka, Japan, Philippines, Nepal, United Arab Emirates, Russia, Italy, Germany, Sweden, Finland, Belgium, Spain, France and the UK.4",2020,"Xu, Chunwen; Luo, Xilian; Yu, Chuck; Cao, Shi-Jie",Indoor and Built Environment,1987841849,#3268,
,CZI,Key points for the prevention and treatment of the novel coronavirus pneumonia in the elderly,10.1177/1938640016668030,,,,"The population is commonly susceptible to the 2019 novel coronavirus(2019-nCoV), especially the elderly with comorbidities.Elderly patients infected with 2019-nCoV tend to have higher rates of severe illnesses and mortality.Immunoaging is an important cause of severe novel coronavirus pneumonia(NCP)in the elderly.Due to the combination of underlying diseases, elderly patients may exhibit a typical manifestations in clinical symptoms, supplementary examinations and pulmonary imaging, deserving particular attention.The general condition of the elderly should be considered during diagnosis and treatment.In addition to routine care and measures such as oxygen therapy, antiviral therapy and respiratory support, treatment of underlying disease, nutritional support, sputum expectoration, complication prevention and psychological support should also be considered for elderly patients.Based on literature review and expert panel discussion, we drafted the Key Points for the Prevention and Treatment of the Novel Coronavirus Pneumonia in the elderly, aiming to provide help with the prevention and treatment of NCP and the reduction of harm to the elderly population.",2020,"CHEN, Qiong; YU, Weiwei; WANG, Lijing; XI, Huan; ZHANG, Qiang; CHEN, Xinyu; HUANG, Kui; LU, Xiang; LIU, Xinmin; ZHANG, Cuntai; WANG, Jianye",Chinese Journal of Geriatrics,2511525332,#2335,
,CZI,"Epidemiological characteristics of 2019-ncoV infections in Shaanxi, China by February 8, 2020",10.1183/13993003.00310-2020,,32139462,,,2020,"Yao, Y.; Tian, Y.; Zhou, J.; Ma, X.; Yang, M.; Wang, S.",The European respiratory journal,3006299216,#5374,
,CZI,"The clinical dynamics of 18 cases of COVID-19 outside of Wuhan, China",10.1183/13993003.00398-2020,,32139464,,,2020,"Wang, L.; Gao, Y. H.; Lou, L. L.; Zhang, G. J.",The European respiratory journal,2613706279,#5274,
,CZI,Q&A: The novel coronavirus outbreak causing COVID-19 A mathematical model for simulating the phase-based transmissibility of a novel coronavirus,10.1186/s12916-020-01533-w 10.1186/s40249-020-00640-3,,,,"The virus responsible for COVID-19, SARS-CoV-2, is in the species SARS-like corona viruses. At 125?nm, it is slightly larger than influenza, SARS and MERS viruses. It is almost certainly a descendant from a bat corona virus of which there are many. The closest is a virus that originated from the Rhinolophus bat which is >?96% homologous with the current SARS-CoV-2 virus. It is only 79% homologous with the original SARS CoV [1].ID - Fisher2020 As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. The virus was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020. This study aimed to develop a mathematical model for calculating the transmissibility of the virus.",2020,"Fisher, Dale; Heymann, David; Chen, Tian-Mu; Rui, Jia; Wang, Qiu-Peng; Zhao, Ze-Yu; Cui, Jing-An; Yin, Ling",BMC Medicine,,#2645,
,CZI,Expert consensus on elderly patients with hip fracture under epidemic of novel coronavirus pneumonia,10.1186/s13104-015-1129-5,,,,"With the spread of novel coronavirus pneumonia (NCP) in December 2019, the management and rehabilitation of elderly patients with hip fractures and protection of medical staff face new challenges, and need to be adjusted appropriately under this very circumstances. Hip fractures in the elderly account for more than half of osteoporotic fractures. Expert group formulate this consensus so as to make better decision against this epidemic and protect patients' families and medical staff. This consensus elaborates not only epidemic condition of NCP, but also general principles of medical admission, treatment and protection for both medical staff and patients, in order to provide some reference and promote the standardization of clinical diagnosis and treatment of elderly patients with hip fractures under the condition of NCP.",2020,"LIU, Guohui; LIU, Ximing; TONG, Xiaoling; WANG, Dongliang; CHEN, Yanxi; CAO, Liehu; LIU, Guodong; LIU, Jing; HU, Yan; HUANG, Biaotong; SHI, Zhongmin; ZHANG, Dianying; HOU, Zhiyong; LIU, Hongjian; TONG, Peijian; SONG, Shaojun; YANG, Lei; WANG, Yong; ZHANG, Lei; LUO, Tao; WANG, Meitang; ZHANG, Peng; ZHANG, Yong; LIN, Haodong; YU, Baoqing; MI, Bobin; ZHANG, Yingze; SU, Jiacan",Chinese Journal of Trauma,2106264008,#2188,
,CZI,Current status of treatment for 2019 novel coronavirus pneumonia,10.1186/s40779-020-0233-6,,,,"2019 novel coronavirus (2019-nCoV) is a new member of coronavirus family that can cause serious respiratory diseases after the emergence of severe acute respiratory syndrome-coronavirus (SARS-CoV) and middle east respiratory syndrome-coronavirus (MERS-CoV). At present, there is no specific antiviral drug targeting 2019-nCoV. In facing of the increasingly serious epidemic of 2019 novel coronavirus pneumonia and the urgent needs in drug treatment strategies, this paper reviewed the current research situation and progress in antiviral treatment for the newly identified disease.",2020,"ZHU, Naiwei; ZHAO, Ping; QI, Zhongtian",Chinese Journal of Microbiology and Immunology,3004824173,#2040,
,CZI,Treatment of 2019 novel coronavirus pneumonia based on the theory of 'three syndromes and three methods',10.1186/s40779-020-0233-6,,,,"The latest diagnosis and treatment plan (4th edition) of 2019 novel coronavirus pneumonia has been issued. The diagnosis and treatment plan highlights the concept of integrated traditional Chinese and Western medicine, and Xuebijing injection was referred for three times. Xuebijing injection was successfully developed based on the theory of 'three syndromes and three methods'. The theory of 'three syndromes and three methods' is a theoretical system of integrated traditional Chinese and Western medicine on critical diseases proposed by Professor Wang Jinda and his team in the 1970s, and it is one of the main contents of Wang Jinda's academic thought. The theory of 'three syndromes and three methods' has a deep foundation of traditional Chinese medicine theory, and it is still being continuously enriched and improved. It is also supported by multiple evidence-based data. Therefore, 'three syndromes and three methods' has rich theoretical connotation and tenacious vitality.",2020,"LI, Zhijun; LI, Yinping; WANG, Bochao",Chinese Critical Care Medicine,3004824173,#2198,
,CZI,Coronavirus disease-2019: is fever an adequate screening for the returning travelers?,10.1186/s41182-020-00201-2,,,,"On Thursday, 30 January 2020, World Health Organization declared Coronavirus disease-2019 (COVID-2019) a Public Health Emergency of International Concern. Since its identification in late December 2019 in Wuhan, Hubei Province, People’s Republic of China, the number of cases imported into other countries is increasing, and the epidemiological map is changing rapidly. On the other hand, body temperature screening (fever) is the major test performed at points of entry, i.e., airports, in the returning travelers in most of the countries with limited resources. However, the recent report on asymptomatic contact transmission of COVID-19 and travelers who passed the symptoms-based screening and tested positive for COVID-19 using reverse transcription polymerase chain reaction (RT-PCR) challenges this approach as body temperature screening may miss travelers incubating the disease or travelers concealing fever during travel. On this note, travel restrictions to and from high risk areas and/or 14 days quarantine of travelers coming from high risk areas are recommended to prevent possible importation of COVID-19. Currently, RT-PCR is a reliable test in detecting both symptomatic and asymptomatic COVID-19.",2020,"Bwire, George M.; Paulo, Linda S.",Tropical Medicine and Health,2145339500,#5077,
,CZI,"The novel coronavirus outbreak in Wuhan, China Development and validation of knowledge, attitude and practice questionnaire for prevention of respiratory tract infections among Malaysian Hajj pilgrims",10.1186/s41256-020-00135-6 10.1186/s12889-020-8269-9,,,,"The novel coronavirus (2019-nCoV, or COVID-19) epidemic first broke out in Wuhan and has been spreading in whole China and the world. The numbers of new infections and deaths in Wuhan are still increasing, which have posed major public health and governance concerns. A series of mandatory actions have been taken by the municipal and provincial governments supported by the central government, such as measures to restrict travels across cities, case detection and contact tracing, quarantine, guidance and information to the public, detection kit development, etc. Challenges such as lacking effective drugs, insufficient hospital services and medical supplies, logistics, etc. have much alleviated with the solidarity of the whole society. The pandemic will definitely be ended with the continuous efforts of both national and international multi-sectoral bodies. Hajj pilgrimage faces numerous challenges including a high prevalence of respiratory tract infection as well as its prevention strategies. The aim of this study was to develop and validate a questionnaire to evaluate knowledge, attitude and practice (KAP) towards respiratory tract infections (RTIs) prevention among Malaysian Hajj pilgrims.",2020,"Zhu, Hengbo; Wei, Li; Niu, Ping; Goni, Mohammed Dauda; Naing, Nyi Nyi; Hasan, Habsah; Wan-Arfah, Nadiah; Deris, Zakuan Zainy; Arifin, Wan Nor; Hussin, Tengku Mohammad Ariff Raja; Abdulrahman, Abdulwali Sabo; Baaba, Aisha Abubakar; Arshad, Muhammad Rafie",Global Health Research and Policy,2999409984,#3234,
,CZI,The novel coronavirus outbreak: what can be learned from China in public reporting?,10.1186/s41256-020-00140-9,,,,"The new coronavirus outbreak gets everyone’s attention. China’s national actions against the outbreak have contributed great contributions to the world. China has been learning from practice for better reporting and is fast to adapt itself. In this article we discuss China’s practice in public reporting and its implications to global health. Confirmed cases, dynamic suspected cases, recovered cases, and deaths have been reported both in accumulative numbers and their daily updates. Some ratio indictors reporting (fatality rate, recovery rate, etc.), trend reporting, and global surveillance have been applied as well. Some improvements can still be made. It is necessary to further explore the influential factors behind the indicators for interventions. Recommendations are made to the World Health Organization and other countries for better public reporting and surveillance.",2020,"Li, Hao; Chen, Xinguang; Huang, Hao",Global Health Research and Policy,3003668884,#4808,
,CZI,Clinical features and high resolutionCT imaging findings of preliminary diagnosis novel coronavirus pneumonia,10.1200/jco.2014.32.15_suppl.11000,,,,"Objective To summarize the clinical characteristics of 141 patients with novel coronavirus pneumonia (NCP) and the imaging characteristics of High Resolution CT(HRCT) in the chest. Methods From January 20, 2020 to 28, 141 NCP patients, 77 males and 64 females, with a median age of 49 (9,87), were retrospectively analyzed. The clinical features, laboratory examination indexes and HRCT findings of 141 NCP patients were analyzed. Results In 141 NCP patients, 38 (26.95%) had a decrease in leukocyte count and 71 (50.35%) had a decrease in lymphocyte ratio. Among 141 NCP patients, 139 (98.58%) had fever (over 37.5 ° C), 106 (75.18%) coughed, 11 (7.80%) had headache, 41 (29.08%) coughed up sputum, 93 (65.96%) had chest distress, and 4 (2.84%) had diarrhea. HRCT of 141 NCP patients were abnormal, 52 (36.88%) showed ground glass shadow (GGO) and patchy shadow, mainly subpleural distribution; 23 (16.31%) showed GGO with focal consolidation; 27 (19.15%) had small patchy blur; 20 (14.18%) had large patchy consolidation; 48 (34.04%) had bronchovascular bundle thickening and vascular perforator sign; 5 (3.55%) had Air bronchus sign; small nodule shadow in 7 cases (4.96%); fibrosis, grid shadow or strip shadow in 5 cases (3.55%); bilateral pleural effusion in 7 cases (4.96%); mediastinal or bilateral hilar lymphadenopathy in 4 cases (2.84%). Conclusions The clinical features and HRCT images of NCP are various. Under the specific epidemiological background of NCP, HRCT scan of chest should be carried out in time to make early warning of disease.",2020,"LU, Xuefang; GONG, Wei; WANG, Li; LI, Liang; XIE, Baojun; PENG, Zhoufeng; ZHA, Yunfei",Chinese Journal of Radiology,2907998690,#2179,
,CZI,Novel coronavirus (SARS-CoV-2) epidemic: a veterinary perspective,10.12834/VetIt.1768.9338.1,,32048818,,,2020,"Lorusso, Alessio; Calistri, Paolo; Petrini, Antonio; Savini, Giovanni; Decaro, Nicola",Vet Ital,3005538648,#754,
,CZI,Novel coronavirus (COVID‑19) epidemic: a veterinary perspective,10.12834/VetIt.2173.11599.1,,,,,2020,"Lorusso, A.; Calistri, P.; Petrini, A.; Savini, G.; Decaro, N.",Veterinaria italiana,,#1559,
,CZI,Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic,10.12932/ap-200220-0772,,32105090,,"As the world is witnessing the epidemic of COVID-19, a disease caused by a novel coronavirus, SARS-CoV-2, emerging genetics and clinical evidences suggest a similar path to those of SARS and MERS. The rapid genomic sequencing and open access data, together with advanced vaccine technology, are expected to give us more knowledge on the pathogen itself, including the host immune response as well as the plan for therapeutic vaccines in the near future. This review aims to provide a comparative view among SARS-CoV, MERS-CoV and the newly epidemic SARS-CoV-2, in the hope to gain a better understanding of the host-pathogen interaction, host immune responses, and the pathogen immune evasion strategies. This predictive view may help in designing an immune intervention or preventive vaccine for COVID-19 in the near future.",2020,"Prompetchara, E.; Ketloy, C.; Palaga, T.",Asian Pacific journal of allergy and immunology,2777011210,#2922,
,CZI,Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19),10.12932/ap-200220-0773,,32134278,,"Last decade witnessed the outbreak of many life-threatening human pathogens including Nipah, Ebola, Chikungunya, Zika, Middle East respiratory syndrome coronavirus (MERS-CoV), Severe Acute respiratory syndrome coronavirus (SARS-CoV) and more recently novel coronavirus (2019-nCoV or SARS-CoV-2). The disease condition associated with novel coronavirus, referred to as Coronavirus disease (COVID-19). The emergence of novel coronavirus in 2019 in Wuhan, China marked the third highly pathogenic coronavirus infecting humans in the 21st century. The continuing emergence of coronaviruses at regular intervals poses a significant threat to human health and economy. Ironically, even after a decade of research on coronavirus, still there are no licensed vaccines or therapeutic agents to treat coronavirus infection which highlights an urgent need to develop effective vaccines or post-exposure prophylaxis to prevent future epidemics. Several clinical, genetic and epidemiological features of COVID-19 resemble SARS-CoV infection. Hence, the research advancements on SARS-CoV treatment might help scientific community in quick understanding of this virus pathogenesis and develop effective therapeutic/prophylactic agents to treat and prevent this infection. Monoclonal antibodies represent the major class of biotherapeutics for passive immunotherapy to fight against viral infection. The therapeutic potential of monoclonal antibodies has been well recognized in the treatment of many diseases. Here, we summarize the potential monoclonal antibody based therapeutic intervention for COVID-19 by considering the existing knowledge on the neutralizing monoclonal antibodies against similar coronaviruses SARS-CoV and MERS-CoV. Further research on COVID-19 pathogenesis could identify appropriate therapeutic targets to develop specific anti-virals against this newly emerging pathogen.",2020,"Shanmugaraj, B.; Siriwattananon, K.; Wangkanont, K.; Phoolcharoen, W.",Asian Pacific journal of allergy and immunology,1633890482,#5213,
,CZI,"Infections without borders: a new coronavirus in Wuhan, China",10.12968/bjon.2020.29.3.166,,32053437,,,2020,"Wood, Cate",Br J Nurs,3006148298,#875,
,CZI,"Brief review of coronavirus for healthcare professionals February 10, 2020",10.13175/swjpcc011-20,,,,"A novel epidemic is challenging the global health care system. Starting from probably November to December 2019, another Coronavirus entered the arena of human pathogens, to be then defined 2019- nCoV [...].",2020,"SA, Robbins RA; Klotz",Southwest Journal of Pulmonary and Critical Care. 2020;20(2):69-70,3006453194,#695,
,CZI,Two clinical cases of Novel coronavirus pneumonia (NCP) in renal transplant recipients,10.1371/journal.pone.0164320,,,,"Objective To explore the clinical features, diagnosis and prognosis of renal transplant recipients with NCP. Method The clinical data of 2 cases of kidney transplant recipients with NCP were retrospectively analyzed. Based onclinical manifestations, blood routine, inflammatory factors, cell immunity, chest CT andtherapeutic effects, the diagnosis and treatment of NCP in kidney transplant recipients (5th edition) were compared to that ofordinary NCP patients. Both recipients developed onset of low andmoderate fever, with no cough or fatigue at the initial stage. Blood routine indicated a normal range of leukocytes,buta significant decrease in lymphocyte counts, increased C-reactive protein (CRP) , and slightly higher procalcitonin (PCT) . The cellular immunity was extremely low, and the chest CT showed multiple patchy ground glass shadows in both lungs. Result After 1 week of onset, both patients had significant disease progression. The pathogenesis and imaging changes were highly similar tothatreported in ordinary NCP patients.Two patients were givensymptomatic supportive treatment by antiviral agents, stop uses ofimmunosuppression agents, small amount of hormone maintenance, intravenous drip of gamma globulin andrespiratory support toavoid secondary infections. At present, the condition of both patients is obviously improved, and renal function is stable. One of them has recovered and was discharged. Conclusion The clinical manifestations of NCP in renal transplant recipients were generally consistent with that of ordinary NCP patients. Although there is no established method for the treatment of NCP, it is effective by stopping uses of immunosuppressive agents, maintaining small and medium doses of hormones, actively restoring immunity, and providing respiratory support in a timely manner.",2020,"TU, Yafang; WU, Xiongfei; LIU, Feng; WANG, Juan; LUO, Yu; CAI, Zhitao; CHEN, Rengui; LIAO, Wenliang; LIU, Na; HUANG, Jin",Chinese Journal of Organ Transplantation,2556328182,#2140,
,CZI,"Communication, transparency key as Canada faces new coronavirus threat",10.1503/cmaj.1095846,,32071113,,,2020,"Glauser, Wendy",CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne,1953687642,#4117,
,CZI,What can early Canadian experience screening for COVID-19 teach us about how to prepare for a pandemic?,10.1503/cmaj.200305,,32144097,,,2020,"Lin, M.; Beliavsky, A.; Katz, K.; Powis, J. E.; Ng, W.; Williams, V.; Science, M.; Groves, H.; Muller, M. P.; Vaisman, A.; Hota, S.; Johnstone, J.; Leis, J. A.",CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne,2482414787,#4856,
,CZI,Laboratory abnormalities in patients with COVID-2019 infection,10.1515/cclm-2020-0198,,32119647,,,2020,"Lippi, Giuseppe; Plebani, Mario",Clin Chem Lab Med,2996021282,#3347,
,CZI,The novel coronavirus (2019-nCoV) outbreak: Think the unthinkable and be prepared to face the challenge,10.1515/dx-2020-0015,,,,,2020,"Lippi, G.; Plebani, M.",Diagnosis,3003218364,#758,
,CZI,"Initial Public Health Response and Interim Clinical Guidance for the 2019 Novel Coronavirus Outbreak - United States, December 31, 2019-February 4, 2020",10.15585/mmwr.mm6905e1,,32027631,,"On December 31, 2019, Chinese health officials reported a cluster of cases of acute respiratory illness in persons associated with the Hunan seafood and animal market in the city of Wuhan, Hubei Province, in central China. On January 7, 2020, Chinese health officials confirmed that a novel coronavirus (2019-nCoV) was associated with this initial cluster (1). As of February 4, 2020, a total of 20,471 confirmed cases, including 2,788 (13.6%) with severe illness,* and 425 deaths (2.1%) had been reported by the National Health Commission of China (2). Cases have also been reported in 26 locations outside of mainland China, including documentation of some person-to-person transmission and one death (2). As of February 4, 11 cases had been reported in the United States. On January 30, the World Health Organization (WHO) Director-General declared that the 2019-nCoV outbreak constitutes a Public Health Emergency of International Concern.(†) On January 31, the U.S. Department of Health and Human Services (HHS) Secretary declared a U.S. public health emergency to respond to 2019-nCoV.(§) Also on January 31, the president of the United States signed a ""Proclamation on Suspension of Entry as Immigrants and Nonimmigrants of Persons who Pose a Risk of Transmitting 2019 Novel Coronavirus,"" which limits entry into the United States of persons who traveled to mainland China to U.S. citizens and lawful permanent residents and their families (3). CDC, multiple other federal agencies, state and local health departments, and other partners are implementing aggressive measures to slow transmission of 2019-nCoV in the United States (4,5). These measures require the identification of cases and their contacts in the United States and the appropriate assessment and care of travelers arriving from mainland China to the United States. These measures are being implemented in anticipation of additional 2019-nCoV cases in the United States. Although these measures might not prevent the eventual establishment of ongoing, widespread transmission of the virus in the United States, they are being implemented to 1) slow the spread of illness; 2) provide time to better prepare health care systems and the general public to be ready if widespread transmission with substantial associated illness occurs; and 3) better characterize 2019-nCoV infection to guide public health recommendations and the development of medical countermeasures including diagnostics, therapeutics, and vaccines. Public health authorities are monitoring the situation closely. As more is learned about this novel virus and this outbreak, CDC will rapidly incorporate new knowledge into guidance for action by CDC and state and local health departments.",2020,"Patel, Anita; Jernigan, Daniel B.; nCo, V. C. D. C. Response Team",MMWR Morb Mortal Wkly Rep,3004775012,#454,
,CZI,"Erratum: Vol. 69, No. 5",10.15585/mmwr.mm6906a5,,32053580,,,2020,"nCo, V. C. D. C. Response Team",MMWR Morb Mortal Wkly Rep,2329951566,#829,
,CZI,"Persons Evaluated for 2019 Novel Coronavirus - United States, January 2020",10.15585/mmwr.mm6906e1,,32053579,,"In December 2019, a cluster of cases of pneumonia emerged in Wuhan City in central China's Hubei Province. Genetic sequencing of isolates obtained from patients with pneumonia identified a novel coronavirus (2019-nCoV) as the etiology (1). As of February 4, 2020, approximately 20,000 confirmed cases had been identified in China and an additional 159 confirmed cases in 23 other countries, including 11 in the United States (2,3). On January 17, CDC and the U.S. Department of Homeland Security's Customs and Border Protection began health screenings at U.S. airports to identify ill travelers returning from Wuhan City (4). CDC activated its Emergency Operations Center on January 21 and formalized a process for inquiries regarding persons suspected of having 2019-nCoV infection (2). As of January 31, 2020, CDC had responded to clinical inquiries from public health officials and health care providers to assist in evaluating approximately 650 persons thought to be at risk for 2019-nCoV infection. Guided by CDC criteria for the evaluation of persons under investigation (PUIs) (5), 210 symptomatic persons were tested for 2019-nCoV; among these persons, 148 (70%) had travel-related risk only, 42 (20%) had close contact with an ill laboratory-confirmed 2019-nCoV patient or PUI, and 18 (9%) had both travel- and contact-related risks. Eleven of these persons had laboratory-confirmed 2019-nCoV infection. Recognizing persons at risk for 2019-nCoV is critical to identifying cases and preventing further transmission. Health care providers should remain vigilant and adhere to recommended infection prevention and control practices when evaluating patients for possible 2019-nCoV infection (6). Providers should consult with their local and state health departments when assessing not only ill travelers from 2019-nCoV-affected countries but also ill persons who have been in close contact with patients with laboratory-confirmed 2019-nCoV infection in the United States.",2020,"Bajema, Kristina L.; Oster, Alexandra M.; McGovern, Olivia L.; Lindstrom, Stephen; Stenger, Mark R.; Anderson, Tara C.; Isenhour, Cheryl; Clarke, Kevin R.; Evans, Mary E.; Chu, Victoria T.; Biggs, Holly M.; Kirking, Hannah L.; Gerber, Susan I.; Hall, Aron J.; Fry, Alicia M.; Oliver, Sara E.; nCo, V. Persons Under Investigation Team; Co, V. Persons Under Investigation Team",MMWR Morb Mortal Wkly Rep,3004490697,#830,
,CZI,"Update: Public Health Response to the Coronavirus Disease 2019 Outbreak - United States, February 24, 2020",10.15585/mmwr.mm6908e1,,32106216,,"An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in Wuhan, Hubei Province, China in December 2019, and has spread throughout China and to 31 other countries and territories, including the United States (1). As of February 23, 2020, there were 76,936 reported cases in mainland China and 1,875 cases in locations outside mainland China (1). There have been 2,462 associated deaths worldwide; no deaths have been reported in the United States. Fourteen cases have been diagnosed in the United States, and an additional 39 cases have occurred among repatriated persons from high-risk settings, for a current total of 53 cases within the United States. This report summarizes the aggressive measures (2,3) that CDC, state and local health departments, multiple other federal agencies, and other partners are implementing to slow and try to contain transmission of COVID-19 in the United States. These measures require the identification of cases and contacts of persons with COVID-19 in the United States and the recommended assessment, monitoring, and care of travelers arriving from areas with substantial COVID-19 transmission. Although these measures might not prevent widespread transmission of the virus in the United States, they are being implemented to 1) slow the spread of illness; 2) provide time to better prepare state and local health departments, health care systems, businesses, educational organizations, and the general public in the event that widespread transmission occurs; and 3) better characterize COVID-19 to guide public health recommendations and the development and deployment of medical countermeasures, including diagnostics, therapeutics, and vaccines. U.S. public health authorities are monitoring the situation closely, and CDC is coordinating efforts with the World Health Organization (WHO) and other global partners. Interim guidance is available at https://www.cdc.gov/coronavirus/index.html. As more is learned about this novel virus and this outbreak, CDC will rapidly incorporate new knowledge into guidance for action by CDC, state and local health departments, health care providers, and communities.",2020,"Jernigan, D. B.",MMWR. Morbidity and mortality weekly report,3004775012,#2845,
,CZI,"Active Monitoring of Persons Exposed to Patients with Confirmed COVID-19 — United States, January–February 2020",10.15585/mmwr.mm6909e1external,,,,"In December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, began in Wuhan, China (1). The disease spread widely in China, and, as of February 26, 2020, COVID-19 cases had been identified in 36 other countries and territories, including the United States. Person-to-person transmission has been widely documented, and a limited number of countries have reported sustained person-to-person spread.* On January 20, state and local health departments in the United States, in collaboration with teams deployed from CDC, began identifying and monitoring all persons considered to have had close contact† with patients with confirmed COVID-19 (2). The aims of these efforts were to ensure rapid evaluation and care of patients, limit further transmission, and better understand risk factors for transmission.",2020,"Sara Rudman; Sarah Scott; Aron J. Hall Alicia M. Fry; Melissa A. Rolfes, Rachel M. Burke; Claire M. Midgley; Alissa Dratch; Marty Fenstersheib; Thomas Haupt; Michelle Holshue; Isaac Ghinai; M. Claire Jarashow; Jennifer Lo; Tristan D. McPherson;",MMWR and Morbidity and Mortality Weekly Report,,#3308,
,CZI,The 2019 novel coronavirus resource,10.16288/j.yczz.20-030,,32102777,,"An ongoing outbreak of a novel coronavirus infection in Wuhan, China since December 2019 has led to 31,516 infected persons and 638 deaths across 25 countries (till 16:00 on February 7, 2020). The virus causing this pneumonia was then named as the 2019 novel coronavirus (2019-nCoV) by the World Health Organization. To promote the data sharing and make all relevant information of 2019-nCoV publicly available, we construct the 2019 Novel Coronavirus Resource (2019nCoVR, https://bigd.big.ac.cn/ncov). 2019nCoVR features comprehensive integration of genomic and proteomic sequences as well as their metadata information from the Global Initiative on Sharing All Influenza Data, National Center for Biotechnology Information, China National GeneBank, National Microbiology Data Center and China National Center for Bioinformation (CNCB)/National Genomics Data Center (NGDC). It also incorporates a wide range of relevant information including scientific literatures, news, and popular articles for science dissemination, and provides visualization functionalities for genome variation analysis results based on all collected 2019-nCoV strains. Moreover, by linking seamlessly with related databases in CNCB/NGDC, 2019nCoVR offers virus data submission and sharing services for raw sequence reads and assembled sequences. In this report, we provide comprehensive descriptions on data deposition, management, release and utility in 2019nCoVR, laying important foundations in aid of studies on virus classification and origin, genome variation and evolution, fast detection, drug development and pneumonia precision prevention and therapy.",2020,"Zhao, W. M.; Song, S. H.; Chen, M. L.; Zou, D.; Ma, L. N.; Ma, Y. K.; Li, R. J.; Hao, L. L.; Li, C. P.; Tian, D. M.; Tang, B. X.; Wang, Y. Q.; Zhu, J. W.; Chen, H. X.; Zhang, Z.; Xue, Y. B.; Bao, Y. M.",Yi chuan = Hereditas,2916654259,#3031,
,CZI,How to conduct clinical research on anesthesiology during epidemic of the novel coronavirus pneumonia: recommendations from the epidemiological perspective,10.17226/10958,,,,"During the outbreak and epidemic of novel coronavirus pneumonia, anesthesiologists are not only the high-risk group of secondary infection, but also undertake tasks to initiate clinical research so that the regular pattern of disease could be summarized, which will product clinical evidences for clinical decision-making and optimization of anesthesia therapy as soon as possible. The clinical research evidences of anaesthesia are of great importance for improving the prevention and control strategy of infectious diseases and implementing relevant measures effectively. The recommendations from the epidemiological perspective are provided on how to conduct clinical research on anesthesiology during epidemic of the novel coronavirus pneumonia in the present paper: (1) The case report and case series research should be initiated promptly once the infectious cases treated in anesthesia department are diagnosed; (2) To focus on need of evidence of decision-making of diagnosis and treatment, to summarize general rules timely and to promote the rapidly production of evidence; (3) To establish a special cohort of novel coronavirus pneumonia so that more prognosis studies could be carried out; (4) To explore the risk factors which result in hospital infection among medical staffs so that hospital infection could be controlled. The purpose of this study is to provide clinicians with methodological suggestions on how to carry out high-quality clinical research in the epidemic period of infectious diseases, and to close the gap between clinical and public health.",2020,"PENG, Xiaoxia; LI, Nan",Chinese Journal of Anesthesiology,1600391151,#2150,
,CZI,COVID-19. The only certainty is the uncertainty,10.17992/lbl.2020.03.469,,32124733,,,2020,"Briem, Haraldur",Laeknabladid,3006338236,#3453,
,CZI,Effects and challenges of Open Science - Academic movements related to the Novel coronavirus (2019-nCoV) and COVID-19,10.18919/jkg.70.3_140,,,,オープンサイエンスの効果はさまざまに論じられてき た。たとえば経済協力開発機構(OECD)の報告書 1) では, 科学研究の効率化,研究の透明性や質の向上,技術革新の 加速,経済への波及効果,地球規模の課題への取り組み, 共同研究の推進などが挙げられている。 折しも 2019 年 12 月以降,新型コロナウイルス(2019- nCoV)の感染が中国の武漢市から世界中に拡大して「地 球規模の課題」となっている。2020 年 1 月 30 日には世 界保健機関(WHO)が国際的な緊急事態であると宣言し た 2)。これに対して各国・地域の研究者,助成機関,学術 出版社といったステークホルダーが最新の研究成果の公開 と再利用を進めて対策にあたるという,まさに「オープン サイエンス」というべき動きが起きている。そこで本稿は 新型コロナウイルスに関する学術界の動向を概観した上 で,今回の事例におけるオープンサイエンスの効果と課題 について考察したい。なお,本稿の記述は 2020 年 2 月 6 日時点の情報に基づいている(情報が古い箇所もあろうか と思いますが,ご容赦を)。,2020,,The Journal of Information Science and Technology Association,871210397,#3003,
,CZI,"The 2019 Novel Coronavirus (2019-nCoV): Novel Virus, Old Challenges",10.20344/amp.13547,,32023427,,,2020,"Duarte, Raquel; Furtado, Isabel; Sousa, Luís; Carvalho, Carlos Filipe Afonso",Acta Med Port,3004691782,#327,
,CZI,Fighting the novel coronavirus: the publication of the Chinese expert consensus on the perinatal and neonatal management for the prevention and control of the 2019 novel coronavirus infection (First edition),10.21037/apm.2020.02.02,,32028773,,,2020,"Editorial, Office",Ann Palliat Med,3004450134,#550,
,CZI,Which lessons shall we learn from the 2019 novel coronavirus outbreak?,10.21037/atm.2020.02.06,,,,,2020,"Mattiuzzi, Camilla; Lippi, Giuseppe",Annals of Translational Medicine,3005487212,#3833,
,CZI,Perinatal and neonatal management plan for prevention and control of 2019 novel coronavirus infection (1st Edition),10.21037/atm.2020.02.20,,32051071,,"Since December 2019, the novel coronavirus (2019-nCoV) infection has been prevalent in China. Due to immaturity of immune function and the possibility of mother-fetal vertical transmission, neonates are particularly susceptible to 2019-nCoV. The perinatal-neonatal departments should cooperate closely and take integrated approaches, and the neonatal intensive care unit should prepare the emergency plan for 2019-nCoV infection as far as possible, so as to ensure the optimal management and treatment of potential victims. According to the latest 2019-nCoV national management plan and the actual situation, the Working Group for the Prevention and Control of Neonatal 2019-nCoV Infection in the Perinatal Period of the Editorial Committee of Chinese Journal of Contemporary Pediatrics puts forward recommendations for the prevention and control of 2019-nCoV infection in neonates.",2020,"Working Group for the, Prevention; Control of Neonatal -nCo, V. Infection in the Perinatal Period of the Editorial Committee of Chinese Journal of Contemporary Pediatrics",Zhongguo Dang Dai Er Ke Za Zhi,3004450134,#810,
,CZI,Management plan for prevention and control of novel coronavirus pneumonia among children in Xiangya Hospital of Central South University,10.21037/atm.2020.02.20,,32051074,,"Since December 2019, an epidemic of novel coronavirus pneumonia (NCP) has occurred in China. How to effectively prevent and control NCP among children with limited resources is an urgent issue to be explored. Under the unified arrangement of the Xiangya Hospital of Central South University, the Department of Pediatrics has formulated an action plan with Xiangya unique model to prevent and control NCP among children according to the current epidemic situation and diagnostic and therapeutic program in China.",2020,"Peng, Jing; Wang, Xia; Yang, Ming-Hua; Wang, Ming-Jie; Zheng, Xiang-Rong",Zhongguo Dang Dai Er Ke Za Zhi,3004450134,#811,
,CZI,Chinese expert consensus on the perinatal and neonatal management for the prevention and control of the 2019 novel coronavirus infection (First edition),10.21037/atm.2020.02.20,,,,"Since December 2019, there has been an outbreak of novel coronavirus (2019-nCoV) infection in China. Two cases of neonates with positive 2019-nCoV tests have been reported. Due to the immature immune system and the possibility of vertical transmission from mother to infant, neonates have become a high-risk group susceptible to 2019-nCoV, which emphasize a close cooperation from both perinatal and neonatal pediatrics. In neonatal intensive care unit (NICU), to prevent and control infection, there should be practical measures to ensure the optimal management of children potentially to be infected. According to the latest 2019-nCoV national management plan and the actual situation, the Chinese Neonatal 2019-nCoV expert working Group has put forward measures on the prevention and control of neonatal 2019-nCoV infection.",2020,"Wang, Laishuan; Shi, Yuan; Xiao, Tiantian; Fu, Jianhua; Feng, Xing; Mu, Dezhi; Feng, Qi; Hei, Mingyan; Hu, Xiaojing; Li, Zhankui; Lu, Guoping; Tang, Zezhong; Wang, Yajuan; Wang, Chuanqing; Xia, Shiwen; Xu, Jianqing; Yang, Yujia; Yang, Jie; Zeng, Mei; Zheng, Jun; Zhou, Wei; Zhou, Xiaoyu; Zhou, Xiaoguang; Du, Lizhong; Lee, Shoo K.; Zhou, Wenhao; Working Comm Perinatal, Neona",Annals of Translational Medicine,3004450134,#4170,
,CZI,Straining the System: Novel Coronavirus (COVID-19) and Preparedness for Concomitant Disasters,10.2105/AJPH.2020.305618,,32053389,,"Just a few weeks before the first confirmed case of novel coronavirus (COVID-19) was reported in the United States, the US Centers for Disease Control and Prevention (CDC) issued a bold promise to the nation: the agency will use its scientific expertise to bring a new level of preparedness in the United States and global health security against current and growing threats, finally eliminate certain diseases, and bring an end to the devastation of epidemics.(1) The current outbreak of COVID-19 reminds us how urgent this promise is and just how critical it is to continue to sustain and strengthen our nation's public health infrastructure. The unprecedented pace of the public health response to COVID-19 has only been possible because of prior investments in public health preparedness. To accelerate our pace and meet the challenges of current and future health threats, we must advance our world-class data and analytics capabilities; maintain and expand our state-of-the-art public health laboratory capacity; continue building a workforce of trusted, expert, public health professionals; sustain our capacity to rapidly respond to outbreaks at their source; and assure a strong global and domestic preparedness capacity. (Am J Public Health. Published online ahead of print February 13, 2020: e1-e2. doi:10.2105/AJPH.2020.305618).",2020,"Smith, Nathaniel; Fraser, Michael",Am J Public Health,3006223500,#878,
,CZI,PANDEMIC HUMAN CORONAVIRUS – CHARACTERIZATION AND COMPARISON OF SELECTED PROPERTIES OF HCOV-SARS AND HCOV-MERS,10.21307/PM-2018.57.1.022,,,,"It: Two Coronaviruses, HCoV-229E and HCoV-OC43, causing generally mild respiratory tract infections in humans, were described in the XX c. Pandemic Coronaviruses were first discovered as late as in the XXI c.: SARS-HCoV in 2002 – causing severe respiratory tract infections (SARS) in China; MERS-HCoV in 2012 – circulating mostly on the Arabian Peninsula. The SARS epidemic ended in 2004 resulting in morbidity of >8000 and >770 deaths, while the MERS epidemic is still ongoing (>2000 ill, >700 deaths) although its intensity decreased. Both viruses are zoonotic and require at least two “host jumps” for the transmission of the infection to humans: for HCoV-SARS – from bat to palm civet and then to human; for HCoV-MERS – from bats to camels and subsequently to humans. Primary mode of transmission is droplet in close contact (<1 m), but both viruses remain active in aerosol (up to 24 h), so infection can be also spread by air (ventilation). The ability for human-to-human transmission is higher for HCoV-SARS than for HCoV-MERS (8 generations vs. 4, respectively). Moreover, there are differences in genome structure and pathogenic mechanisms: different receptor, cell entry mechanism, different way of host response modulation (e.g. inhibition of IFNβ cascade), etc. Probably, these differences influence the overall manifestation of the disease in humans. Infection caused by HCoV-MERS might manifest itself as ARDS, a mild-mannered and asymptomatic disease. HCoV-SARS infections seem to be associated with severe disease only. In this paper, a comparison of the structure of these viruses, the mechanisms underlying their ability to cross the interspecies barrier and to multiply in the human body, including modulation of IFNβ cascade, as well as routes of infection transmission and symptoms caused, were presented.",2020,"Pancer, Katarzyna W.",Postępy Mikrobiologii,,#1790,
,CZI,"Early Transmissibility Assessment of a Novel Coronavirus in Wuhan, China",10.2139/ssrn.3524675,,,,"Between December 1, 2019 and January 26, 2020, nearly 3000 cases of respiratory illness caused by a novel coronavirus originating in Wuhan, China have been reported. In this short analysis, we combine publicly available cumulative case data from the ongoing outbreak with phenomenological modeling methods to conduct an early transmissibility assessment. Our model suggests that the basic reproduction number associated with the outbreak (at time of writing) may range from 2.0 to 3.1. Though these estimates are preliminary and subject to change, they are consistent with previous findings regarding the transmissibility of the related SARS-Coronavirus and indicate the possibility of epidemic potential.",,"Majumder, Maimuna and Mandl, Kenneth D.",SSRN,3001343166,#26,
,CZI,Coronavirus Disease COVID-19: A New Threat to Public Health,10.2174/1568026620999200305144319,,32133964,,,2020,"Kumar, S.; Poonam; Rathi, B.",Current topics in medicinal chemistry,2004242782,#4784,
,CZI,China Coronavirus Outbreak: All the Latest Updates,10.2174/1568026620999200305144537,,32133963,,,2020,"Scotti, Luciana; Scotti, Marcus T.",Current topics in medicinal chemistry,2999409984,#5206,
,CZI,Effective Chemicals against Novel Coronavirus (COVID-19) in China,10.2174/1568026620999200305145032,,32133962,,,2020,"Liu, Wei; Zhu, Hai-Liang; Duan, Yongtao",Current topics in medicinal chemistry,3005929298,#5452,
,CZI,COVID-19: Perspectives on the Potential Novel Global Threat,10.2174/1574887115999200228100745,,32116200,,,2020,"Gentile, Ivan; Abenavoli, Ludovico",Reviews on recent clinical trials,3006113744,#4112,
,CZI,Wuhan 2019 Novel Coronavirus Pneumonia: A Case Report of Serial Computed Tomographic Findings in a Female Patient (Preprint),10.2196/18129,,,,"UNSTRUCTURED Background: From December 2019, the 2019 Novel Coronavirus (2019-nCoV) Pneumonia broke out in Wuhan, China. In this study, we present the finding of serial computed tomography in a female patient with 2019-nCoV. Case presentation: We report a 40-year-old female who presented with the symptoms of fever, chest tightness, and fatigue. She was further diagnosed with 2019-nCoV confirmed by rRT-PCR. In terms of her chest CT findings, patchy consolidation shadows, and ground-glass opacities (GGOs) rapidly progressed in both lungs, peripherally. After treatment, the previous lesions were almost absorbed, leaving the fibrous lesions. Conclusions: If there is a history of fever or contact with the epidemic area, combined with the above CT findings, it is necessary to detect the nucleic acid of new coronavirus in time.",,"Wei, Jiangping; Xu, Huaxiang; Xiong, Jingliang; Shen, Qinglin; Fan, Bing; Ye, Chenglong; Dong, Wentao; Hu, Fangfang",,3005148615,#720,
,CZI,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: Chest CT Findings,10.2214/AJR.14.13021,,,,,2014,"Ajlan, Amr M.; Ahyad, Rayan A.; Jamjoom, Lamia Ghazi; Alharthy, Ahmed; Madani, Tariq A.",American Journal of Roentgenology,2112136274,#2448,
,CZI,Déjà Vu or Jamais Vu? How the Severe Acute Respiratory Syndrome Experience Influenced a Singapore Radiology Department's Response to the Coronavirus Disease (COVID-19) Epidemic,10.2214/AJR.20.22927,,32130047,,"OBJECTIVE. This article shares the ground operational perspective of how a tertiary hospital radiology department in Singapore is responding to the coronavirus disease (COVID-19) epidemic. This same department was also deeply impacted by the severe acute respiratory syndrome (SARS) outbreak in 2003. CONCLUSION. Though similar to SARS, the COVID-19 outbreak has several differences. We share how lessons from 2003 are applied and modified in our ongoing operational response to this evolving novel pathogen.",2020,"Cheng, Lionel Tim-Ee; Chan, Lai Peng; Tan, Ban Hock; Chen, Robert Chun; Tay, Kiang Hiong; Ling, Moi Lin; Tan, Bien Soo",AJR Am J Roentgenol,,#4602,
,CZI,Coronavirus Disease 2019 (COVID-19): Role of Chest CT in Diagnosis and Management,10.2214/AJR.20.22954,,32130038,,"OBJECTIVE. The objective of our study was to determine the misdiagnosis rate of radiologists for coronavirus disease 2019 (COVID-19) and evaluate the performance of chest CT in the diagnosis and management of COVID-19. The CT features of COVID-19 are reported and compared with the CT features of other viruses to familiarize radiologists with possible CT patterns. MATERIALS AND METHODS. This study included the first 51 patients with a diagnosis of COVID-19 infection confirmed by nucleic acid testing (23 women and 28 men; age range, 26-83 years) and two patients with adenovirus (one woman and one man; ages, 58 and 66 years). We reviewed the clinical information, CT images, and corresponding image reports of these 53 patients. The CT images included images from 99 chest CT examinations, including initial and follow-up CT studies. We compared the image reports of the initial CT study with the laboratory test results and identified CT patterns suggestive of viral infection. RESULTS. COVID-19 was misdiagnosed as a common infection at the initial CT study in two inpatients with underlying disease and COVID-19. Viral pneumonia was correctly diagnosed at the initial CT study in the remaining 49 patients with COVID-19 and two patients with adenovirus. These patients were isolated and obtained treatment. Ground-glass opacities (GGOs) and consolidation with or without vascular enlargement, interlobular septal thickening, and air bronchogram sign are common CT features of COVID-19. The The ""reversed halo"" sign and pulmonary nodules with a halo sign are uncommon CT features. The CT findings of COVID-19 overlap with the CT findings of adenovirus infection. There are differences as well as similarities in the CT features of COVID-19 compared with those of the severe acute respiratory syndrome. CONCLUSION. We found that chest CT had a low rate of missed diagnosis of COVID-19 (3.9%, 2/51) and may be useful as a standard method for the rapid diagnosis of COVID-19 to optimize the management of patients. However, CT is still limited for identifying specific viruses and distinguishing between viruses.",2020,"Li, Yan; Xia, Liming",AJR Am J Roentgenol,3006643024,#4517,
,CZI,Radiology Perspective of Coronavirus Disease 2019 (COVID-19): Lessons From Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome,10.2214/ajr.20.22969,,32108495,,"OBJECTIVE. Since the outbreak of the novel coronavirus pulmonary illness coronavirus disease 2019 (COVID-19) in China, more than 79,000 people have contracted the virus worldwide. The virus is rapidly spreading with human-to-human transmission despite imposed precautions. Because similar pulmonary syndromes have been reported from other strains of the coronavirus family, our aim is to review the lessons from imaging studies obtained during severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) outbreaks. CONCLUSION. The review of experiences with the MERS and SARS outbreaks will help us better understand the role of the radiologist in combating the outbreak of COVID-19. The known imaging manifestations of the novel coronavirus and the possible unknowns will also be discussed.",2020,"Hosseiny, M.; Kooraki, S.; Gholamrezanezhad, A.; Reddy, S.; Myers, L.",AJR. American journal of roentgenology,3006645647,#2833,
,CZI,"CT Features of Coronavirus Disease 2019 (COVID-19) Pneumonia in 62 Patients in Wuhan, China",10.2214/ajr.20.22975,,32134681,,"OBJECTIVE. The purpose of this study was to investigate 62 subjects in Wuhan, China, with laboratory-confirmed coronavirus disease (COVID-19) pneumonia and describe the CT features of this epidemic disease. MATERIALS AND METHODS. A retrospective study of 62 consecutive patients with laboratory-confirmed COVID-19 pneumonia was performed. CT images and clinical data were reviewed. Two thoracic radiologists evaluated the distribution and CT signs of the lesions and also scored the extent of involvement of the CT signs. The Mann-Whitney U test was used to compare lesion distribution and CT scores. The chi-square test was used to compare the CT signs of early-phase versus advanced-phase COVID-19 pneumonia. RESULTS. A total of 62 patients (39 men and 23 women; mean [+/- SD] age, 52.8 +/- 12.2 years; range, 30-77 years) with COVID-19 pneumonia were evaluated. Twenty-four of 30 patients who underwent routine blood tests (80.0%) had a decreased lymphocyte count. Of 27 patients who had their erythrocyte sedimentation rate and high-sensitivity C-reactive protein level assessed, 18 (66.7%) had an increased erythrocyte sedimentation rate, and all 27 (100.0%) had an elevated high-sensitivity C-reactive protein level. Multiple lesions were seen on the initial CT scan of 52 of 62 patients (83.9%). Forty-eight of 62 patients (77.4%) had predominantly peripheral distribution of lesions. The mean CT score for the upper zone (3.0 +/- 3.4) was significantly lower than that for the middle (4.5 +/- 3.8) and lower (4.5 +/- 3.7) zones (p = 0.022 and p = 0.020, respectively), and there was no significant difference in the mean CT score of the middle and lower zones (p = 1.00). The mean CT score for the anterior area (4.4 +/- 4.1) was significantly lower than that for the posterior area (7.7 +/- 6.3) (p = 0.003). CT findings for the patients were as follows: 25 patients (40.3%) had ground-glass opacities (GGO), 21 (33.9%), consolidation; 39 (62.9%), GGO plus a reticular pattern; 34 (54.8%), vacuolar sign; 28 (45.2%), microvascular dilation sign; 35 (56.5%), fibrotic streaks; 21 (33.9%), a subpleural line; and 33 (53.2%), a subpleural transparent line. With regard to bronchial changes seen on CT, 45 patients (72.6%) had air bronchogram, and 11 (17.7%) had bronchus distortion. In terms of pleural changes, CT showed that 30 patients (48.4%) had pleural thickening, 35 (56.5%) had pleural retraction sign, and six (9.7%) had pleural effusion. Compared with early-phase disease (= 7 days after the onset of symptoms), advanced-phase disease (8-14 days after the onset of symptoms) was characterized by significantly increased frequencies of GGO plus a reticular pattern, vacuolar sign, fibrotic streaks, a subpleural line, a subpleural transparent line, air bronchogram, bronchus distortion, and pleural effusion; however, GGO significantly decreased in advanced-phase disease. CONCLUSION. CT examination of patients with COVID-19 pneumonia showed a mixed and diverse pattern with both lung parenchyma and the interstitium involved. Identification of GGO and a single lesion on the initial CT scan suggested early-phase disease. CT signs of aggravation and repair coexisted in advanced-phase disease. Lesions presented with a characteristic multifocal distribution in the middle and lower lung regions and in the posterior lung area. A decreased lymphocyte count and an increased high-sensitivity C-reactive protein level were the most common laboratory findings.",2020,"Zhou, S.; Wang, Y.; Zhu, T.; Xia, L.",AJR. American journal of roentgenology,3006354146,#5523,
,CZI,Relation Between Chest CT Findings and Clinical Conditions of Coronavirus Disease (COVID-19) Pneumonia: A Multicenter Study,10.2214/AJR.20.22976,,32125873,,"OBJECTIVE. The increasing number of cases of confirmed coronavirus disease (COVID-19) in China is striking. The purpose of this study was to investigate the relation between chest CT findings and the clinical conditions of COVID-19 pneumonia. MATERIALS AND METHODS. Data on 101 cases of COVID-19 pneumonia were retrospectively collected from four institutions in Hunan, China. Basic clinical characteristics and detailed imaging features were evaluated and compared between two groups on the basis of clinical status: nonemergency (mild or common disease) and emergency (severe or fatal disease). RESULTS. Patients 21-50 years old accounted for most (70.2%) of the cohort, and five (5.0%) patients had disease associated with a family outbreak. Most patients (78.2%) had fever as the onset symptom. Most patients with COVID-19 pneumonia had typical imaging features, such as ground-glass opacities (GGO) (87 [86.1%]) or mixed GGO and consolidation (65 [64.4%]), vascular enlargement in the lesion (72 [71.3%]), and traction bronchiectasis (53 [52.5%]). Lesions present on CT images were more likely to have a peripheral distribution (88 [87.1%]) and bilateral involvement (83 [82.2%]) and be lower lung predominant (55 [54.5%]) and multifocal (55 [54.5%]). Patients in the emergency group were older than those in the non-emergency group. Architectural distortion, traction bronchiectasis, and CT involvement score aided in evaluation of the severity and extent of the disease. CONCLUSION. Patients with confirmed COVID-19 pneumonia have typical imaging features that can be helpful in early screening of highly suspected cases and in evaluation of the severity and extent of disease. Most patients with COVID-19 pneumonia have GGO or mixed GGO and consolidation and vascular enlargement in the lesion. Lesions are more likely to have peripheral distribution and bilateral involvement and be lower lung predominant and multifocal. CT involvement score can help in evaluation of the severity and extent of the disease.",2020,"Zhao, Wei; Zhong, Zheng; Xie, Xingzhi; Yu, Qizhi; Liu, Jun",AJR Am J Roentgenol,2055651857,#3238,
,CZI,Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy,10.23812/20-Editorial-Kritas,,32013309,,"Coronavirus, which can cause respiratory syndrome, to date has affected over seventeen thousand individuals, especially in China. Coronavirus is interspecies and can also be transmitted from man to man, with an incubation ranging from 1 to 14 days. Human coronavirus infections can induce not only mild to severe respiratory diseases, but also inflammation, high fever, cough, acute respiratory tract infection and dysfunction of internal organs that may lead to death. Coronavirus infection (regardless of the various types of corona virus) is primarily attacked by immune cells including mast cells (MCs), which are located in the submucosa of the respiratory tract and in the nasal cavity and represent a barrier of protection against microorganisms. Viral activate MCs release early inflammatory chemical compounds including histamine and protease; while late activation provokes the generation of pro-inflammatory IL-1 family members including IL-1, IL-6 and IL-33. Here, we propose for the first time that inflammation by coronavirus may be inhibited by anti-inflammatory cytokines belonging to the IL-1 family members.",2019,"Kritas, S. K.; Ronconi, G.; Caraffa, Al; Gallenga, C. E.; Ross, R.; Conti, P.",J Biol Regul Homeost Agents,2119445255,#3716,
,CZI,Identification of Coronavirus Isolated from a Patient in Korea with COVID-19,10.24171/j.phrp.2020.11.1.02,,,,"Objectives Following reports of patients with unexplained pneumonia at the end of December 2019 in Wuhan, China, the causative agent was identified as coronavirus (SARS-CoV-2), and the 2019 novel coronavirus disease was named COVID-19 by the World Health Organization. Putative patients with COVID-19 have been identified in South Korea, and attempts have been made to isolate the pathogen from these patients. Methods Upper and lower respiratory tract secretion samples from putative patients with COVID-19 were inoculated onto cells to isolate the virus. Full genome sequencing and electron microscopy were used to identify the virus. Results The virus replicated in Vero cells and cytopathic effects were observed. Full genome sequencing showed that the virus genome exhibited sequence homology of more than 99.9% with SARS-CoV-2 which was isolated from patients from other countries, for instance China. Sequence homology of SARS-CoV-2 with SARS-CoV, and MERS-CoV was 77.5% and 50%, respectively. Coronavirus-specific morphology was observed by electron microscopy in virus-infected Vero cells. Conclusion SARS-CoV-2 was isolated from putative patients with unexplained pneumonia and intermittent coughing and fever. The isolated virus was named BetaCoV/Korea/KCDC03/2020.",2020,"Han, Jeong-Min Kim; Yoon-Seok, Chung; Hye Jun, Jo; Nam-Joo, Lee; Mi Seon, Kim; Sang Hee, Woo; Sehee, Park; Jee Woong, Kim; Heui Man, Kim; Myung, Guk",Osong Public Health and Research Perspectives,3005657121,#2631,
,CZI,Early Epidemiological and Clinical Characteristics of 28 Cases of Coronavirus Disease in South Korea,10.24171/j.phrp.2020.11.1.03,,,,"The first confirmed case of coronavirus disease 2019 (COVID-19) in South Korea was reported in January 2020, with 28 confirmed cases reported as of February 14th, 2020. The epidemiological and clinical characteristics of all 28 cases were analyzed in response to this disease. Methods The epidemiological characteristics and early clinical features of the 28 patients from Korea with confirmed COVID-19 were analyzed using COVID-19 reporting and surveillance data and the epidemiological investigation reports prepared by the rapid response team. Results There were 16 patients that entered Korea from foreign countries: Wuhan, China (11 patients), Zhuhai, China, (1 patient), Singapore (2 patients), Japan (1 patient), and Thailand (1 patient). The early symptoms were fever, sore throat, cough or sputum production, chills, and muscle ache. Three patients were asymptomatic, however, 18 developed pneumonia. Of the 28 cases, 16 were index cases imported from abroad, with 10 cases of secondary infection originating in Korea, and the route of transmission still under investigation for 2 patients. The 10 patients with secondary infection were infected from contact with family members or acquaintances of primary patients, and the suspected sites of transmission were mostly at home. Conclusion COVID-19 in Korea was spread by 16 infected individuals traveling from other countries, leading to second-generation cases. The initial symptoms were mostly minor, but the disease was infectious at this stage, resulting from close contact, particularly at home. Establishing an early detection strategy for COVID-19 is crucial for managing the transmission of the disease.",2020,,Osong Public Health and Research Perspectives,2981256933,#2688,
,CZI,Contact Transmission of COVID-19 in South Korea: Novel Investigation Techniques for Tracing Contacts,10.24171/j.phrp.2020.11.1.09,,,,"In the epidemiological investigation of an infectious disease, investigating, classifying, tracking, and managing contacts by identifying the patient’s route are important for preventing further transmission of the disease. However, omissions and errors in previous activities can occur when the investigation is performed through only a proxy interview with the patient. To overcome these limitations, methods that can objectively verify the patient’s claims (medical facility records, Global Positioning System, card transactions, and closed-circuit television) were used for the recent ongoing coronavirus disease 2019 contact investigations in South Korea.",2020,,Osong Public Health and Research Perspectives,119142419,#2687,
,CZI,Data sharing for novel coronavirus (COVID-19),10.2471/blt.20.251561,,32132744,,,2020,"Moorthy, Vasee; Henao Restrepo, Ana Maria; Preziosi, Marie-Pierre; Swaminathan, Soumya",Bulletin of the World Health Organization,3006223500,#4910,
,CZI,Expert Recommendations for Tracheal Intubation in Critically ill Patients with Noval Coronavirus Disease 2019,10.24920/003724,,32102726,,"Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), is a highly contagious disease. It firstly appeared in Wuhan, Hubei province of China in December 2019. During the next two months, it moved rapidly throughout China and spread to multiple countries through infected persons travelling by air. Most of the infected patients have mild symptoms including fever, fatigue and cough. But in severe cases, patients can progress rapidly and develop to the acute respiratory distress syndrome, septic shock, metabolic acidosis and coagulopathy. The new coronavirus was reported to spread via droplets, contact and natural aerosols from human-to-human. Therefore, high-risk aerosol-producing procedures such as endotracheal intubation may put the anesthesiologists at high risk of nosocomial infections. In fact, SARS-CoV-2 infection of anesthesiologists after endotracheal intubation for confirmed COVID-19 patients have been reported in hospitals in Wuhan. The expert panel of airway management in Chinese Society of Anaesthesiology has deliberated and drafted this recommendation, by which we hope to guide the performance of endotracheal intubation by frontline anesthesiologists and critical care physicians. During the airway management, enhanced droplet/airborne PPE should be applied to the health care providers. A good airway assessment before airway intervention is of vital importance. For patients with normal airway, awake intubation should be avoided and modified rapid sequence induction is strongly recommended. Sufficient muscle relaxant should be assured before intubation. For patients with difficult airway, good preparation of airway devices and detailed intubation plans should be made.",2020,"Zuo, M. Z.; Huang, Y. G.; Ma, W. H.; Xue, Z. G.; Zhang, J. Q.; Gong, Y. H.; Che, L.",Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih,2017345465,#3041,
,CZI,COVID-19 (Novel Coronavirus 2019) - recent trends,10.26355/eurrev_202002_20378,,32141569,,"The World Health Organization (WHO) has issued a warning that, although the 2019 novel coronavirus (COVID-19) from Wuhan City (China), is not pandemic, it should be contained to prevent the global spread. The COVID-19 virus was known earlier as 2019-nCoV. As of 12 February 2020, WHO reported 45,171 cases and 1115 deaths related to COVID-19. COVID-19 is similar to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) virus in its pathogenicity, clinical spectrum, and epidemiology. Comparison of the genome sequences of COVID-19, SARS-CoV, and Middle East Respiratory Syndrome coronavirus (MERS-CoV) showed that COVID-19 has a better sequence identity with SARS-CoV compared to MERS CoV. However, the amino acid sequence of COVID-19 differs from other coronaviruses specifically in the regions of 1ab polyprotein and surface glycoprotein or S-protein. Although several animals have been speculated to be a reservoir for COVID-19, no animal reservoir has been already confirmed. COVID-19 causes COVID-19 disease that has similar symptoms as SARS-CoV. Studies suggest that the human receptor for COVID-19 may be angiotensin-converting enzyme 2 (ACE2) receptor similar to that of SARS-CoV. The nucleocapsid (N) protein of COVID-19 has nearly 90% amino acid sequence identity with SARS-CoV. The N protein antibodies of SARS-CoV may cross react with COVID-19 but may not provide cross-immunity. In a similar fashion to SARS-CoV, the N protein of COVID-19 may play an important role in suppressing the RNA interference (RNAi) to overcome the host defense. This mini-review aims at investigating the most recent trend of COVID-19.",2020,"Kannan, S.; Shaik Syed Ali, P.; Sheeza, A.; Hemalatha, K.",European review for medical and pharmacological sciences,3005943294,#4760,
,CZI,"Novel coronavirus 2019-nCoV: prevalence, biological and clinical characteristics comparison with SARS-CoV and MERS-CoV",10.26355/eurrev_202002_20379,,32141570,,"OBJECTIVE: Human infections with zoonotic coronavirus contain emerging and reemerging pathogenic characteristics which have raised great public health concern. This study aimed at investigating the global prevalence, biological and clinical characteristics of novel coronavirus, Wuhan China (2019-nCoV), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection outbreaks. MATERIALS AND METHODS: The data on the global outbreak of ""2019-nCoV, SARS-CoV, and MERS-CoV"" were obtained from World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), concerned ministries and research institutes. We also recorded the information from research documents published in global scientific journals indexed in ISI Web of Science and research centers on the prevalence, biological and clinical characteristics of 2019-nCoV, SARS-CoV, and MERS-CoV. RESULTS: Worldwide, SARS-CoV involved 32 countries, with 8422 confirmed cases and 916 (10.87%) casualties from November 2002 to August 2003. MERS-CoV spread over 27 states, causing 2496 cases and 868 (34.77%) fatalities during the period April 2012 to December 2019. However, the novel coronavirus 2019-nCoV spread swiftly the global borders of 27 countries. It infected 34799 people and resulted in 724 (2.08%) casualties during the period December 29, 2019 to February 7, 2020. The fatality rate of coronavirus MERS-CoV was (34.77%) higher than SARS-CoV (10.87%) and 2019-nCoV (2.08%); however, the 2019-nCoV transmitted rapidly in comparison to SARS-CoV and MERS-CoV. CONCLUSIONS: The novel coronavirus 2019-nCoV has diverse epidemiological and biological characteristics, making it more contagious than SARS-CoV and MERS-CoV. It has affected more people in a short time period compared to SARS-CoV and MERS-CoV, although the fatality rate of MERS-CoV was higher than SARS-CoV and 2019-nCoV. The major clinical manifestations in coronavirus infections 2019-nCoV, MERS-CoV, and SARS CoV are fever, chills, cough, shortness of breath, generalized myalgia, malaise, drowsy, diarrhea, confusion, dyspnea, and pneumonia. Global health authorities should take immediate measures to prevent the outbreaks of such emerging and reemerging pathogens across the globe to minimize the disease burden locally and globally.",2020,"Meo, S. A.; Alhowikan, A. M.; Al-Khlaiwi, T.; Meo, I. M.; Halepoto, D. M.; Iqbal, M.; Usmani, A. M.; Hajjar, W.; Ahmed, N.",European review for medical and pharmacological sciences,3005122137,#4906,
,CZI,Burden of acute respiratory disease of epidemic and pandemic potential in the WHO Eastern Mediterranean Region: A literature review,10.26719/2016.22.7.509,,,,"There are gaps in the knowledge about the burden of severe respiratory disease in the Eastern Mediterranean Region (EMR). This literature review was therefore conducted to describe the burden of epidemic-and pandemic-prone acute respiratory infections (ARI) in the Region which may help in the development of evidence-based disease prevention and control policies. Relevant published and unpublished reports were identified from searches of various databases; 83 documents fulfilled the search criteria. The infections identified included: ARI, avian influenza A(H5N1), influenza A(H1N1)pdm09 and Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Pneumonia and ARIs were leading causes of disease and death in the Region. Influenza A(H1N1) was an important cause of morbidity during the 2009 pandemic. This review provides a descriptive summary of the burden of acute respiratory diseases in the Region, but there still remains a lack of necessary data. On observe des lacunes en matière de connaissances concernant la charge des maladies respiratoires sévères dans la Région de la Méditerranée orientale. La présente analyse documentaire détaille la charge des infections respiratoires aiguës (IRA) à potentiel épidémique et pandémique dans la Région, ce qui peut aider à l'élaboration de politiques et programmes de prévention et de lutte contre les maladies reposant sur des données factuelles. Des articles pertinents publiés et non publiés ont été identifiés grâce à des recherches dans différentes bases de données ; 83 documents satisfaisaient à nos critères de recherche. Les infections identifiées comprenaient les infections respiratoires aiguës (IRA), la grippe aviaire A(H5N1), la grippe A(H1N1)pdm09 et l'infection par le coronavirus du syndrome respiratoire du Moyen-Orient (MERS-CoV). La pneumonie et les IRA constituaient les principales causes de morbidité et de mortalité dans la Région. La grippe A(H1N1) était une cause importante de morbidité durant la pandémie de 2009. Cette analyse fournit un résumé descriptif de la charge des maladies respiratoires aiguës dans la Région mais il existe toujours une lacune concernant les donneés nécessaires à cet égard.",2016,"Abubakar, A.; Malik, M.; Pebody, R. G.; Elkholy, A. A.; Khan, W.; Bellos, A.; Mala, P.",Eastern Mediterranean Health Journal,2529381635,#2453,
,CZI,Coronavirus disease 2019 outbreak: Preparedness and readiness of countries in the eastern mediterranean region,10.26719/2020.26.2.136,,,,,2020,"Al-Mandhari, A.; Samhouri, D.; Abubakar, A.; Brennan, R.",Eastern Mediterranean Health Journal,3006609801,#5026,
,CZI,"First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020",10.2807/1560-7917.es.2020.25.6.2000094,,,,"A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 [1]. On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from some clustered cases [2]. Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 (COVID-19). As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization (WHO) European Region [3-5]. Here we describe the epidemiology of the first cases of COVID-19 in this region, excluding cases reported in the United Kingdom (UK), as at 21 February 2020. The study includes a comparison between cases detected among travellers from China and cases whose infection was acquired due to subsequent local transmission.%R doi:https://doi.org/10.2807/1560-7917.ES.2020.25.9.2000178",2020,"Spiteri, Gianfranco; Fielding, James; Diercke, Michaela; Campese, Christine; Enouf, Vincent; Gaymard, Alexandre; Bella, Antonino; Sognamiglio, Paola; Sierra Moros, Maria José; Riutort, Antonio Nicolau; Demina, Yulia V.; Mahieu, Romain; Broas, Markku; Bengnér, Malin; Buda, Silke; Schilling, Julia; Filleul, Laurent; Lepoutre, Agnès; Saura, Christine; Mailles, Alexandra; Levy-Bruhl, Daniel; Coignard, Bruno; Bernard-Stoecklin, Sibylle; Behillil, Sylvie; van der Werf, Sylvie; Valette, Martine; Lina, Bruno; Riccardo, Flavia; Nicastri, Emanuele; Casas, Inmaculada; Larrauri, Amparo; Salom Castell, Magdalena; Pozo, Francisco; Maksyutov, Rinat A.; Martin, Charlotte; Van Ranst, Marc; Bossuyt, Nathalie; Siira, Lotta; Sane, Jussi; Tegmark-Wisell, Karin; Palmérus, Maria; Broberg, Eeva K.; Beauté, Julien; Jorgensen, Pernille; Bundle, Nick; Pereyaslov, Dmitriy; Adlhoch, Cornelia; Pukkila, Jukka; Pebody, Richard; Olsen, Sonja; Ciancio, Bruno Christian",Eurosurveillance,3006007867,#4442,
,CZI,Coronavirus latest: WHO officially names disease COVID-19,10.2807/1560-7917.es.2020.25.6.2000094,,,,"The World Health Organization has officially named the disease caused by the coronavirus COVID-19. This will replace various monikers and hashtags given to the emerging illness over the past few weeks. Most recently, on 8 February, China’s National Health Commission decided to temporarily call the disease novel coronavirus pneumonia, or NCP. But because viruses continue to spread from animals to people, this coronavirus won’t be novel for long.",2020,Science,Science,3006007867,#687,
,CZI,Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak,10.2807/1560-7917.es.2020.25.6.2000110,,,,"Infections with 2019-nCoV can spread from person to person, and in the earliest phase of the outbreak the basic reproductive number was estimated to be around 2.2, assuming a mean serial interval of 7.5 days [2]. The serial interval was not precisely estimated, and a potentially shorter mean serial interval would have corresponded to a slightly lower basic reproductive number. Control measures and changes in population behaviour later in January should have reduced the effective reproductive number. However, it is too early to estimate whether the effective reproductive number has been reduced to below the critical threshold of 1 because cases currently being detected and reported would have mostly been infected in mid- to late-January. Average delays between infection and illness onset have been estimated at around 5–6 days, with an upper limit of around 11-14 days [2,5], and delays from illness onset to laboratory confirmation added a further 10 days on average [2].",,"Cowling, Benjamin J; Leung, Gabriel M",Eurosurveillance,3006044875,#675,
,CZI,Evaluation of a quantitative RT-PCR assay for the detection of the emerging coronavirus SARS-CoV-2 using a high throughput system,10.2807/1560-7917.ES.2020.25.9.2000152,,,,"The ability to quickly confirm or clear suspected cases is crucial during global outbreak scenarios, especially when clinical manifestations are difficult to distinguish from other respiratory infections such as influenza, molecular diagnostics is key for detection of the emerging virus. A variety of suitable assays were made available early on during the course of the outbreak, notably by Corman et al. and others [4,5]. However, their implementation in the diagnostics laboratory usually relies on manual PCR setups requiring a high degree of human interaction for execution and interpretation, thus limiting their capacity to be scaled up for handling large numbers of samples. In this study we report the analytical evaluation of a laboratory-developed test for the detection of SARS-CoV-2 using the open channel (utility channel) of the cobas 6800 system.%U https://eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.9.2000152",2020,"Pfefferle, Susanne; Reucher, Svenja; Nörz, Dominic; Lütgehetmann, Marc",Eurosurveillance,2033377462,#4473,
,CZI,"Rapid establishment of laboratory diagnostics for the novel coronavirus SARS-CoV-2 in Bavaria, Germany, February 2020",10.2807/1560-7917.ES.2020.25.9.2000173,,,,"In connection with the ongoing outbreak of a novel coronavirus in the province Hubei and surrounding areas in China, it was expected that Europe would also be confronted with the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as infections in travellers in several Asian countries outside of China were confirmed shortly after the announcement of the outbreak in Wuhan [1-4]. Therefore, it was necessary to rapidly implement adequately quick and sensitive diagnostic assays for outbreak management of SARS-CoV-2 in public health laboratories. As soon as the World Health Organization (WHO) published the first protocols for real-time RT-PCR assays, the Bavarian Food and Health Authority started to implement them. We ordered control material and oligonucleotides (see details below) in week 4 and ran our first SARS-CoV-2 assays on 27 January (week 5). On the same day, the first German case of coronavirus disease 2019 (COVID-19) was diagnosed in Bavaria [1]. In the following days, health authorities implemented comprehensive measures to prevent further transmission of SARS-CoV-2, including testing of contact persons. We initially used the protocol based on the E gene and RdRp gene developed by the German Consiliary Laboratory for Coronaviruses hosted at the Charité in Berlin [5]. Real-time RT-PCR was initially performed with the QuantiTect Virus +Rox Vial kit (QIAGEN, Hilden, Germany) on the Bio-Rad CFX96 Touch Real-Time PCR Detection System (Bio-Rad, Feldkirchen, Germany). The kit was chosen for its frequent and successful use in our laboratory with other assays and its immediate availability. Primers and probes were used as described [5] and provided by TIB Molbiol (Berlin, Germany). Control material was ordered from the European Virus Archive (EVAg) and consisted of synthetic Wuhan coronavirus 2019 E gene control (reference number 026N-03866) and SARS-CoV Frankfurt 1 RNA (reference number 004N-02005) [6]. In addition, the control of LightMix Modular Wuhan CoV RdRP-gene (TibMolbiol, Berlin, Germany) was used for the SARS-CoV-2 specific assay. Respiratory samples (nasopharyngeal swabs or sputum) were obtained from patients and contact persons. Sputum samples were diluted in 2 mL phosphate buffered saline (PBS). RNA was extracted using the QIAamp Bio Robot kit (QIAGEN) on a Hamilton Microlab Star (Hamilton, Bonaduz, Switzerland). As at 1 March, 87,024 cases and 2,979 associated deaths have been reported worldwide [1]. The vast majority of the deaths (96%) have been reported in China [1]. Despite the high number of cases reported globally, estimates of the severity pyramid of disease and case fatality rate remain very uncertain; one large study conducted in China estimated that the majority (81%) of the cases were mild (i.e. non-pneumonia or mild pneumonia), 14% were severe (e.g. with dyspnoea) and 5% were in a critical condition (i.e. respiratory failure, septic shock and/or multiple organ dysfunction/failure) [2]. The case fatality ratio was 2.3% [2]. Despite extraordinary containment measures implemented in China, including the enforced lockdown of several cities and closures of schools, the virus has spread throughout the country and internationally [2]. It is too early to predict with any certainty the epidemiological developments over the coming weeks, but the possibility of widespread community transmission becoming established throughout the EU/EEA is becoming increasingly likely.",2020,"Konrad, Regina; Eberle, Ute; Dangel, Alexandra; Treis, Bianca; Berger, Anja; Bengs, Katja; Fingerle, Volker; Liebl, Bernhard; Ackermann, Nikolaus; Sing, Andreas",Eurosurveillance,3005538648,#4532,
,CZI,Updated rapid risk assessment from ECDC on the outbreak of COVID-19: increased transmission globally,10.2807/1560-7917.ES.2020.25.9.2003051,,,,"The European Centre for Disease Prevention and Control (ECDC) provides regularly updated information on coronavirus disease-2019 (COVID-19) relevant to Europe on a dedicated webpage. Besides general information including Q&As, daily case counts, and maps with disease distribution, examples of latest updates comprise: Resource estimation for contact tracing, quarantine and monitoring activities for COVID-19 cases in the EU/EEA, Guidance for wearing and removing personal protective equipment in healthcare settings for the care of patients with suspected or confirmed COVID-19 and Checklist for hospitals preparing for the reception and care of coronavirus 2019 (COVID-19) patients. ECDC also publishes regular risk assessments and the Box below contains the summary from the fifth update published on 2 March 2020.%U https://eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.9.2003051",2020,"team, Eurosurveillance editorial",Eurosurveillance,3006211350,#4434,
,CZI,Perinatal novel coronavirus infection: a case report,10.2807/ese.18.08.20406-en,,,,"We hereby reported the diagnosis, treatment process and perinatal outcome of a patient with novel coronavirus infection in perinatal period. The pregnant woman delivered a boy by cesarean section at 37 +2 gestational weeks due to severe liver dysfunction. She subsequently had a high fever 2 days later, and novel coronavirus infection was confirmed by nucleic acid test in a throat swab. After a 12-day isolation and support treatment, her two consecutive throat swab results for novel coronavirus turned negative and she was discharged. The novel coronavirus was tested in the patient's blood, urine, breast milk as well as the neonatal throat swab, and the results were all negative. The neonate had an elevated myocardial enzyme, but was otherwise well and was discharged after 14-day isolation with normal myocardial enzyme.",2020,"ZHUANG, Siying; GUO, Juanjuan; CAO, Yuming; CHEN, Huijun; XU, Dan; LI, Jiafu; ZHANG, Yuanzhen",Chinese Journal of Perinatal Medicine,1736130314,#2038,
,CZI,Air Medical Evacuation of Nepalese Citizen During Epidemic of COVID-19 from Wuhan to Nepal,10.31729/jnma.4857,,,,"In December 2019, the world was disrupted by the news of a new strain of virus known as Novel Corona virus, taking lives of many in China. Wuhan, the capital of Central China’s Hubei province is said to be the place where the outbreak started. The city went on a lockdown as the disease spread rapidly. After the lockdown, most countries like India and Bangladesh airlifted their citizens who were studying in Wuhan. Similarly, Nepal also has many youth studying medicine in Wuhan. Pleas for help from the students reached the government. This was a first encounter of such experience for Nepal government. With the help of Health Emergency Organizing committee, Epidemiology and Disease Control Division, Nepal Army Hospital, Nepal Police Hospital, Waste Management team, Nepal Ambulance service, Tribhuwan Airport and Royal Airlines the government of Nepal planned, organized and successfully brought back all the 175 students on 15 the February, 2019 from Wuhan, China. The aim of the present article is to share the experience, the challenges faced and recommendations for future similar cases.",2020,"Thapa, Bibek Rajbhandari; Naveen, Phuyal; Bikal, Shrestha; Moon",Journal of Nepal Medical Association,2074966216,#4431,
,CZI,The laboratory risk assessment and control testing 2019 novel coronavirus in biosafety class II laboratories,10.3201/eid2605.200146,,,,"The outbreak of 2019 Novel Coronavirus (2019-nCoV) has spread from Wuhan to the whole country. After the Spring Festival, workers will return to workplace and students will return to school. There is an increasing risk of 2019-nCoV cases being imported into provinces and cities. In order to promote the prevention and control of 2019-nCoV infection, reduce the risk of transmission in medical institutions, and ensure medical quality and medical safety, it is necessary to carry out the detection test of 2019-nCoV in biosafety class II laboratory. In order to achieve the goal of zero infection of the laboratory personnel, different preventive measures should be taken to assess the risk of the experimental activities.",2020,"HUA, Wenhao; SHENG, Linjun; SONG, Lihong; WANG, Qingtao",Chinese Journal of Laboratory Medicine,3006320625,#2258,
,CZI,"Lack of Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, China",10.3201/eid2606.200287,,32134381,,A woman with 2019 novel coronavirus disease in her 35th week of pregnancy delivered an infant by cesarean section in a negative-pressure operating room. The infant was negative for severe acute respiratory coronavirus 2. This case suggests that mother-to-child transmission is unlikely for this virus.,2020,"Li, Y.; Zhao, R.; Zheng, S.; Chen, X.; Wang, J.; Sheng, X.; Zhou, J.; Cai, H.; Fang, Q.; Yu, F.; Fan, J.; Xu, K.; Chen, Y.; Sheng, J.",Emerging infectious diseases,2116732940,#4834,
,CZI,"2019-nCoV acute respiratory disease, Australia: Epidemiology Report 1 (Reporting week 26 January - 1 February 2020)",10.33321/cdi.2020.44.13,,32027812,,"This is the first epidemiological report of novel coronavirus (2019-nCoV) acute respiratory disease infections reported in Australia at 19:00 Australian Eastern Daylight Time [AEDT] 1 February 2020. It includes data on Australian cases notified during the week 26 January to 1 February 2020 and in the previous week (19 to 25 January 2020), the international situation and current information on the severity, transmission and spread of the 2019-nCoV infection.",2020,"nCo, V. National Incident Room Surveillance Team",Commun Dis Intell (2018),3004914321,#475,
,CZI,"COVID-19, Australia: Epidemiology Report 2 (Reporting week ending 19:00 AEDT 8 February 2020)",10.33321/cdi.2020.44.14,,32050080,,"This is the second epidemiological report for coronavirus disease (COVID-19), previously known as novel coronavirus (2019-nCoV), reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 8 February 2020. It includes data on Australian cases notified during the week ending 19:00 AEDT 8 February 2020, the international situation and current information on the severity, transmission and spread of the COVID-19 infection.",2020,"Team, Covid- National Incident Room Surveillance",Commun Dis Intell (2018),3006338236,#727,
,CZI,"COVID-19, Australia: Epidemiology Report 3 (Reporting week ending 19:00 AEDT 15 February 2020)",10.33321/cdi.2020.44.15,,32074480,,"This is the third epidemiological report for coronavirus disease 2019 (COVID-19), previously known as novel coronavirus (2019-nCoV), from the virus now known as SARS-CoV-2, reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 15 February 2020. It includes data on the COVID-19 Australian cases, the international situation and current information on the severity, transmission and spread.",2020,"Team, Covid- National Incident Room Surveillance",Commun Dis Intell (2018),3006338236,#1485,
,CZI,"COVID-19, Australia: Epidemiology Report 4 (Reporting week ending 19:00 AEDT 22 February 2020)",10.33321/cdi.2020.44.17,,32098616,,"This is the fourth epidemiological report for coronavirus disease 2019 (COVID-19), reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 22 February 2020. It includes data on COVID-19 cases diagnosed in Australia, the international situation and a review of current evidence.",2020,"Team, Covid- National Incident Room Surveillance",Commun Dis Intell (2018),3006338236,#2377,
,CZI,"COVID-19, Australia: Epidemiology Report 5 (Reporting week ending 19:00 AEDT 29 February 2020)",10.33321/cdi.2020.44.20,,32126197,,"This is the fifth epidemiological report for coronavirus disease 2019 (COVID-19), reported in Australia as at 19:00 Australian Eastern Daylight Time [AEDT] 29 February 2020. It includes data on COVID-19 cases diagnosed in Australia, the international situation and a review of current evidence.",2020,"Team, Covid- National Incident Room Surveillance",Commun Dis Intell (2018),3006338236,#3292,
,CZI,The Fight against the 2019-nCoV Outbreak: an Arduous March Has Just Begun,10.3346/jkms.2020.35.e56,,,,<![CDATA[No abstract available.]]>,2020,"YOO, Jin Hong",Journal of Korean Medical Science,3003274018,#1017,
,CZI,"The First Case of 2019 Novel Coronavirus Pneumonia Imported into Korea from Wuhan, China: Implication for Infection Prevention and Control Measures",10.3346/jkms.2020.35.e61,,,,"In December 2019, a viral pneumonia outbreak caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV), began in Wuhan, China. We report the epidemiological and clinical features of the first patient with 2019-nCoV pneumonia imported into Korea from Wuhan. This report suggests that in the early phase of 2019-nCoV pneumonia, chest radiography would miss patients with pneumonia and highlights taking travel history is of paramount importance for early detection and isolation of 2019-nCoV cases.",2020,"Kim, Jin Yong",Journal of Korean Medical Science,3004790666,#3705,
,CZI,Case of the Index Patient Who Caused Tertiary Transmission of COVID-19 Infection in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Infected Pneumonia Monitored by Quantitative RT-PCR,10.3346/jkms.2020.35.e79,,,,"Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, ß-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.",2020,"Lim, Jaegyun; Jeon, Seunghyun; Shin, Hyun Young; Kim, Moon Jung; Seong, Yu Min; Lee, Wang Jun; Choe, Kang Won; Kang, Yu Min; Lee, Baeckseung; Park, Sang Joon",J Korean Med Sci,3005657121,#861,
,CZI,THREE NOTICEABLE ISSUES ON NOVEL CORONAVIRUS: A QUICK LOOK FROM VIETNAM’S CIRCUMSTANCES,10.33546/bnj.1058,,,,"Novel Coronavirus officially COVID-19 has been detected since December 2019 and it has become a global health issue concern today. According to the statistics from the Vietnam’s Ministry of Health, until 13February 2020, Vietnam has fifteen positive cases with COVID-19, which one of those is a 3-month-old baby (Ministry of Health, 2020). It is estimated that the COVID-19 outbreak will be reached the top in the next ten days due to the excessive worrying and wrong behaviors towards the virus (Thu, 2020). In this letter, the author presents three noticeable issues based on the current situation in Vietnam and efforts that nurses should do",2020,"Tuyen, Le Thi Thanh",6,,#881,
,CZI,"Understanding Unreported Cases in the COVID-19 Epidemic Outbreak in Wuhan, China, and the Importance of Major Public Health Interventions",10.3390/biology9030050,,,,"We develop a mathematical model to provide epidemic predictions for the COVID-19 epidemic in Wuhan, China. We use reported case data up to 31 January 2020 from the Chinese Center for Disease Control and Prevention and the Wuhan Municipal Health Commission to parameterize the model. From the parameterized model, we identify the number of unreported cases. We then use the model to project the epidemic forward with varying levels of public health interventions. The model predictions emphasize the importance of major public health interventions in controlling COVID-19 epidemics.",2020,"Liu, Zhihua; Magal, Pierre; Seydi, Ousmane; Webb, Glenn",Biology,3005301080,#5460,
,CZI,Rigidity of the Outer Shell Predicted by a Protein Intrinsic Disorder Model Sheds Light on the COVID-19 (Wuhan-2019-nCoV) Infectivity,10.3390/biom10020331,,,,"The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries. With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential to affect up to two-thirds of the world population, COVID-19 is considered by the World Health Organization (WHO) to be a global health emergency. The speed of spread and infectivity of COVID-19 (also known as Wuhan-2019-nCoV) are dramatically exceeding those of the Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). In fact, since September 2012, the WHO has been notified of 2494 laboratory-confirmed cases of infection with MERS-CoV, whereas the 2002–2003 epidemic of SARS affected 26 countries and resulted in more than 8000 cases. Therefore, although SARS, MERS, and COVID-19 are all the result of coronaviral infections, the causes of the coronaviruses differ dramatically in their transmissibility. It is likely that these differences in infectivity of coronaviruses can be attributed to the differences in the rigidity of their shells which can be evaluated using computational tools for predicting intrinsic disorder predisposition of the corresponding viral proteins.",2020,"Goh, Gerard Kian-Meng; Dunker, A. Keith; Foster, James A.; Uversky, Vladimir N.",Biomolecules,2794226826,#1308,
,CZI,Antiviral Action of Tryptanthrin Isolated from Strobilanthes cusia Leaf against Human Coronavirus NL63 Outbreak of Novel Coronavirus (SARS-Cov-2): First Evidences From International Scientific Literature and Pending Questions,10.3390/biom10030366 10.3390/healthcare8010051,,,,"Strobilanthes cusia (Nees) Kuntze is a Chinese herbal medicine used in the treatment of respiratory virus infections. The methanol extract of S. cusia leaf contains chemical components such as β-sitosterol, indirubin, tryptanthrin, betulin, indigodole A, and indigodole B that have diverse biological activities. However, the antiviral action of S. cusia leaf and its components against human coronavirus remains to be elucidated. Human coronavirus NL63 infection is frequent among immunocompromised individuals, young children, and in the elderly. This study investigated the anti-Human coronavirus NL63 (HCoV-NL63) activity of the methanol extract of S. cusia leaf and its major components. The methanol extract of S. cusia leaf effectively inhibited the cytopathic effect (CPE) and virus yield (IC50 = 0.64 μg/mL) in HCoV-NL63-infected cells. Moreover, this extract potently inhibited the HCoV-NL63 infection in a concentration-dependent manner. Among the six components identified in the methanol extract of S. cusia leaf, tryptanthrin and indigodole B (5aR-ethyltryptanthrin) exhibited potent antiviral activity in reducing the CPE and progeny virus production. The IC50 values against virus yield were 1.52 μM and 2.60 μM for tryptanthrin and indigodole B, respectively. Different modes of time-of-addition/removal assay indicated that tryptanthrin prevented the early and late stages of HCoV-NL63 replication, particularly by blocking viral RNA genome synthesis and papain-like protease 2 activity. Notably, tryptanthrin (IC50 = 0.06 μM) and indigodole B (IC50 = 2.09 μM) exhibited strong virucidal activity as well. This study identified tryptanthrin as the key active component of S. cusia leaf methanol extract that acted against HCoV-NL63 in a cell-type independent manner. The results specify that tryptanthrin possesses antiviral potential against HCoV-NL63 infection. On 31 December, 2019, a cluster of 27 pneumonia cases of unknown etiology was reported by Chinese health authorities in Wuhan City (China) [...]",2020,"Tsai, Yu-Chi; Lee, Chia-Lin; Yen, Hung-Rong; Chang, Young-Sheng; Lin, Yu-Ping; Huang, Su-Hua; Lin, Cheng-Wen; Amodio, Emanuele; Vitale, Francesco; Cimino, Livia; Casuccio, Alessandra; Tramuto, Fabio",Biomolecules,2977112956,#2528,
,CZI,Advance in human coronaviruses research of host interactions,10.3390/diseases4030026,,,,"2019-novel coronavirus (2019-nCoV) is a highly pathogenic human CoV that first emerged in Wuhan in 2019.2019-nCoV has a zoonotic origin and poses a major threat to public health.However, little is known about the viral factors contributing to the high virulence of 2019-nCoV.Many animal viruses, including CoVs, encode proteins that interfere with host gene expression, including those involved in antiviral immune responses, and these viral proteins are often major virulence factors.Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory infection.In the past 17 years, the onset of 2019-nCoV, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans.The recent study of HCoVs-host interactions has contributed extensively to our understanding of infection pathogenesis of 2019-nCoV.This review discuss various host physiopathologic mechanism, such as apoptosis, innate immunity, endoplasmic reticulum (ER) stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs and provides evidence for the intensive investigate of 2019-nCoV infection.",2020,"GU, Yanni; SHEN, Chaobin; CHEN, Tongxin",Chinese Journal of Applied Clinical Pediatrics,2491014331,#2275,
,CZI,"On the Coronavirus (COVID-19) Outbreak and the Smart City Network: Universal Data Sharing Standards Coupled with Artificial Intelligence (AI) to Benefit Urban Health Monitoring and Management Epidemiological Identification of A Novel Pathogen in Real Time: Analysis of the Atypical Pneumonia Outbreak in Wuhan, China, 2019—2020",10.3390/healthcare8010046ER - Y - EJOU 10.3390/jcm9030637ER -,,,,"As the Coronavirus (COVID-19) expands its impact from China, expanding its catchment into surrounding regions and other countries, increased national and international measures are being taken to contain the outbreak. The placing of entire cities in ‘lockdown’ directly affects urban economies on a multi-lateral level, including from social and economic standpoints. This is being emphasised as the outbreak gains ground in other countries, leading towards a global health emergency, and as global collaboration is sought in numerous quarters. However, while effective protocols in regard to the sharing of health data is emphasised, urban data, on the other hand, specifically relating to urban health and safe city concepts, is still viewed from a nationalist perspective as solely benefiting a nation’s economy and its economic and political influence. This perspective paper, written one month after detection and during the outbreak, surveys the virus outbreak from an urban standpoint and advances how smart city networks should work towards enhancing standardization protocols for increased data sharing in the event of outbreaks or disasters, leading to better global understanding and management of the same. Virological tests have now shown conclusively that a novel coronavirus is causing the 2019–2020 atypical pneumonia outbreak in Wuhan, China. We demonstrate that non-virological descriptive characteristics could have determined that the outbreak is caused by a novel pathogen in advance of virological testing. Characteristics of the ongoing outbreak were collected in real time from two medical social media sites. These were compared against characteristics of eleven pathogens that have previously caused cases of atypical pneumonia. The probability that the current outbreak is due to “Disease X” (i.e., previously unknown etiology) as opposed to one of the known pathogens was inferred, and this estimate was updated as the outbreak continued. The probability (expressed as a percentage) that Disease X is driving the outbreak was assessed as over 29% on 31 December 2019, one week before virus identification. After some specific pathogens were ruled out by laboratory tests on 5 January 2020, the inferred probability of Disease X was over 49%. We showed quantitatively that the emerging outbreak of atypical pneumonia cases is consistent with causation by a novel pathogen. The proposed approach, which uses only routinely observed non-virological data, can aid ongoing risk assessments in advance of virological test results becoming available.",2020,"Allam, Zaheer; Jones, David S.; Jung, Sung-mok; Kinoshita, Ryo; Thompson, N. Robin; Linton, M. Natalie; Yang, Yichi; Akhmetzhanov, R. Andrei; Nishiura, Hiroshi",Healthcare,,#2685,
,CZI,Prediction of Epidemic Spread of the 2019 Novel Coronavirus Driven by Spring Festival Transportation in China: A Population-Based Study,10.3390/ijerph17051679,,,,"After the 2019 novel coronavirus (2019-nCoV) outbreak, we estimated the distribution and scale of more than 5 million migrants residing in Wuhan after they returned to their hometown communities in Hubei Province or other provinces at the end of 2019 by using the data from the 2013–2018 China Migrants Dynamic Survey (CMDS). We found that the distribution of Wuhan’s migrants is centred in Hubei Province (approximately 75%) at a provincial level, gradually decreasing in the surrounding provinces in layers, with obvious spatial characteristics of circle layers and echelons. The scale of Wuhan’s migrants, whose origins in Hubei Province give rise to a gradient reduction from east to west within the province, and account for 66% of Wuhan’s total migrants, are from the surrounding prefectural-level cities of Wuhan. The distribution comprises 94 districts and counties in Hubei Province, and the cumulative percentage of the top 30 districts and counties exceeds 80%. Wuhan’s migrants have a large proportion of middle-aged and high-risk individuals. Their social characteristics include nuclear family migration (84%), migration with families of 3–4 members (71%), a rural household registration (85%), and working or doing business (84%) as the main reason for migration. Using a quasi-experimental analysis framework, we found that the size of Wuhan’s migrants was highly correlated with the daily number of confirmed cases. Furthermore, we compared the epidemic situation in different regions and found that the number of confirmed cases in some provinces and cities in Hubei Province may be underestimated, while the epidemic situation in some regions has increased rapidly. The results are conducive to monitoring the epidemic prevention and control in various regions.",2020,"Fan, Changyu; Liu, Linping; Guo, Wei; Yang, Anuo; Ye, Chenchen; Jilili, Maitixirepu; Ren, Meina; Xu, Peng; Long, Hexing; Wang, Yufan",International Journal of Environmental Research and Public Health,3002747665,#4088,
,CZI,Immediate Psychological Responses and Associated Factors during the Initial Stage of the 2019 Coronavirus Disease (COVID-19) Epidemic among the General Population in China,10.3390/ijerph17051729,,,,"Background: The 2019 coronavirus disease (COVID-19) epidemic is a public health emergency of international concern and poses a challenge to psychological resilience. Research data are needed to develop evidence-driven strategies to reduce adverse psychological impacts and psychiatric symptoms during the epidemic. The aim of this study was to survey the general public in China to better understand their levels of psychological impact, anxiety, depression, and stress during the initial stage of the COVID-19 outbreak. The data will be used for future reference. Methods: From 31 January to 2 February 2020, we conducted an online survey using snowball sampling techniques. The online survey collected information on demographic data, physical symptoms in the past 14 days, contact history with COVID-19, knowledge and concerns about COVID-19, precautionary measures against COVID-19, and additional information required with respect to COVID-19. Psychological impact was assessed by the Impact of Event Scale-Revised (IES-R), and mental health status was assessed by the Depression, Anxiety and Stress Scale (DASS-21). Results: This study included 1210 respondents from 194 cities in China. In total, 53.8% of respondents rated the psychological impact of the outbreak as moderate or severe; 16.5% reported moderate to severe depressive symptoms; 28.8% reported moderate to severe anxiety symptoms; and 8.1% reported moderate to severe stress levels. Most respondents spent 20–24 h per day at home (84.7%); were worried about their family members contracting COVID-19 (75.2%); and were satisfied with the amount of health information available (75.1%). Female gender, student status, specific physical symptoms (e.g., myalgia, dizziness, coryza), and poor self-rated health status were significantly associated with a greater psychological impact of the outbreak and higher levels of stress, anxiety, and depression (p < 0.05). Specific up-to-date and accurate health information (e.g., treatment, local outbreak situation) and particular precautionary measures (e.g., hand hygiene, wearing a mask) were associated with a lower psychological impact of the outbreak and lower levels of stress, anxiety, and depression (p < 0.05). Conclusions: During the initial phase of the COVID-19 outbreak in China, more than half of the respondents rated the psychological impact as moderate-to-severe, and about one-third reported moderate-to-severe anxiety. Our findings identify factors associated with a lower level of psychological impact and better mental health status that can be used to formulate psychological interventions to improve the mental health of vulnerable groups during the COVID-19 epidemic.",2020,"Wang, Cuiyan; Pan, Riyu; Wan, Xiaoyang; Tan, Yilin; Xu, Linkang; Ho, S. Cyrus; Ho, C. Roger",International Journal of Environmental Research and Public Health,1994584686,#5504,
,CZI,A Meta-Analysis of Multiple Whole Blood Gene Expression Data Unveils a Diagnostic Host-Response Transcript Signature for Respiratory Syncytial Virus,10.3390/ijms21051831ER -,,,,"Respiratory syncytial virus (RSV) is one of the major causes of acute lower respiratory tract infection worldwide. The absence of a commercial vaccine and the limited success of current therapeutic strategies against RSV make further research necessary. We used a multi-cohort analysis approach to investigate host transcriptomic biomarkers and shed further light on the molecular mechanism underlying RSV-host interactions. We meta-analyzed seven transcriptome microarray studies from the public Gene Expression Omnibus (GEO) repository containing a total of 922 samples, including RSV, healthy controls, coronaviruses, enteroviruses, influenzas, rhinoviruses, and coinfections, from both adult and pediatric patients. We identified > 1500 genes differentially expressed when comparing the transcriptomes of RSV-infected patients against healthy controls. Functional enrichment analysis showed several pathways significantly altered, including immunologic response mediated by RSV infection, pattern recognition receptors, cell cycle, and olfactory signaling. In addition, we identified a minimal 17-transcript host signature specific for RSV infection by comparing transcriptomic profiles against other respiratory viruses. These multi-genic signatures might help to investigate future drug targets against RSV infection.",2020,"Barral-Arca, Ruth; Gómez-Carballa, Alberto; Cebey-López, Miriam; Bello, Xabier; Martinón-Torres, Federico; Salas, Antonio",International Journal of Molecular Sciences,2794338276,#5053,
,CZI,"Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak Risk Management Analysis for Novel Coronavirus in Wuhan, China",10.3390/jcm9020388 10.3390/jrfm13020022,,,,"Background: In December 2019, an outbreak of respiratory illness caused by a novel coronavirus (2019-nCoV) emerged in Wuhan, China and has swiftly spread to other parts of China and a number of foreign countries. The 2019-nCoV cases might have been under-reported roughly from 1 to 15 January 2020, and thus we estimated the number of unreported cases and the basic reproduction number, R0, of 2019-nCoV. Methods: We modelled the epidemic curve of 2019-nCoV cases, in mainland China from 1 December 2019 to 24 January 2020 through the exponential growth. The number of unreported cases was determined by the maximum likelihood estimation. We used the serial intervals (SI) of infection caused by two other well-known coronaviruses (CoV), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) CoVs, as approximations of the unknown SI for 2019-nCoV to estimate R0. Results: We confirmed that the initial growth phase followed an exponential growth pattern. The under-reporting was likely to have resulted in 469 (95% CI: 403−540) unreported cases from 1 to 15 January 2020. The reporting rate after 17 January 2020 was likely to have increased 21-fold (95% CI: 18−25) in comparison to the situation from 1 to 17 January 2020 on average. We estimated the R0 of 2019-nCoV at 2.56 (95% CI: 2.49−2.63). Conclusion: The under-reporting was likely to have occurred during the first half of January 2020 and should be considered in future investigation. Recently, a novel coronavirus pneumonia (2019–nCoV) outbreak occurred in Wuhan, China, rapidly spreading first to the whole country, and then globally, causing widespread concern. From the perspectives of early warning and identification of risk, risk monitoring, and analysis, as well as risk management and handling, we propose corresponding solutions and recommendations, which include institutional cooperation, and to inform national and international policy-makers.",2020,"Zhao, Shi; Musa, Salihu S.; Lin, Qianying; Ran, Jinjun; Yang, Guangpu; Wang, Weiming; Lou, Yijun; Yang, Lin; Gao, Daozhou; He, Daihai; Wang, Maggie H.; Yue, Xiao-Guang; Shao, Xue-Feng; Li, Y. Rita; Crabbe, James C. M.; Mi, Lili; Hu, Siyan; Baker, S. Julien; Liang, Gang",Journal of Clinical Medicine,3004200727,#158,
,CZI,The report of two cases infection with novel coronavirus (2019-ncov) after kidney transplantation and the association literature analyzation,10.3390/jcm9020419,,,,"Objective To investigate the clinical experience of patients with novel coronavirus (2019-ncov) infection after kidney transplantation. Method Clinical data of two patients with 2019-nCoV infection after renal transplantationin Jan 2020 Renmin Hospital of Wuhan Universiyt were retrospectively analyzed.Case 1 was a 48-year-old male with CMV pneumonia secondary to 2019-nCoV infection at 4 months after transplantation. CT imaging showed multiple patchy ground-glass images of both lungs. Case 2 was a 59-year-old male, who was screened positive for 2019-nCoV nucleic acid due to fever at 9 days after renal transplantation and showed no clinical manifestations of pneumonia. After diagnosis, case 1 was transferred to a designated hospital for isolation. Treatment regimens: cefoperazone sulbactam sodium + linezolid to resist infection, gamma globulin to enhance immunity function, methylprednisolone to control inflammatory response, antiviral regimens including arbidol tablets + lopina-velitonavir tablets. Case 2 was treated with isolated treatment in a single room. The treatment plan included anti-infection (cefoperazone sulbactam sodium), enhancing immunity function (gamma globulin), antivirus therapy with arbidol and other symptomatic treatment. Result Follow up with 3 weeks, case 1 recovered with renal dysfunction, nucleic acid test with nasopharyngeal swabs turned negative, and pulmonary imaging improved. Case 2 showed no obvious clinical symptoms, and the nucleic acid test of nasopharyngeal swabs turned negative for 3 times. Conclusion Renal transplant recipients should receive fine protection to avoid exposure to high-risk environments. Diagnosis should be defined with combination of clinical manifestations, nucleic acid test and pulmonary imaging. At present, there are no antiviral drugs and symptomatic treatment is the main choice.",2020,"QIU, Tao; WANG, Jingyue; ZHOU, Jiangqiao; ZOU, Jilin; CHEN, Zhongbao; MA, Xiaoxiong; ZHANG, Long",Chinese Journal of Organ Transplantation,3004658686,#2425,
,CZI,"Initial Cluster of Novel Coronavirus (2019-nCoV) Infections in Wuhan, China Is Consistent with Substantial Human-to-Human Transmission Novel Coronavirus Outbreak in Wuhan, China, 2020: Intense Surveillance Is Vital for Preventing Sustained Transmission in New Locations",10.3390/jcm9020488 10.3390/jcm9020498ER -,,,,"Reanalysis of the epidemic curve from the initial cluster of cases with novel coronavirus (2019-nCoV) in December 2019 indicates substantial human-to-human transmission. It is possible that the common exposure history at a seafood market in Wuhan originated from the human-to-human transmission events within the market, and the early, strong emphasis that market exposure indicated animal-to-human transmission was potentially the result of observer bias. To support the hypothesis of zoonotic origin of 2019-nCoV stemming from the Huanan seafood market, the index case should have had exposure history related to the market and the virus should have been identified from animals sold at the market. As these requirements remain unmet, zoonotic spillover at the market must not be overemphasized. The outbreak of pneumonia originating in Wuhan, China, has generated 24,500 confirmed cases, including 492 deaths, as of 5 February 2020. The virus (2019-nCoV) has spread elsewhere in China and to 24 countries, including South Korea, Thailand, Japan and USA. Fortunately, there has only been limited human-to-human transmission outside of China. Here, we assess the risk of sustained transmission whenever the coronavirus arrives in other countries. Data describing the times from symptom onset to hospitalisation for 47 patients infected early in the current outbreak are used to generate an estimate for the probability that an imported case is followed by sustained human-to-human transmission. Under the assumptions that the imported case is representative of the patients in China, and that the 2019-nCoV is similarly transmissible to the SARS coronavirus, the probability that an imported case is followed by sustained human-to-human transmission is 0.41 (credible interval [0.27, 0.55]). However, if the mean time from symptom onset to hospitalisation can be halved by intense surveillance, then the probability that an imported case leads to sustained transmission is only 0.012 (credible interval [0, 0.099]). This emphasises the importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak will not become a global pandemic.",2020,"Nishiura, Hiroshi; Linton, Natalie M.; Akhmetzhanov, Andrei R.; Thompson, Robin N.",Journal of Clinical Medicine,3005599914,#667,
,CZI,Risk Assessment of Novel Coronavirus COVID-19 Outbreaks Outside China,10.3390/jcm9020571,,,,"We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; and (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number R loc ). We found that in countries with low connectivity to China but with relatively high R loc , the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low R loc benefit the most from policies that further reduce R loc . Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia, and Europe. We investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.",2020,"Boldog, Péter; Tekeli, Tamás; Vizi, Zsolt; Dénes, Attila; Bartha, Ferenc A.; Röst, Gergely",Journal of Clinical Medicine,3005847234,#1328,
,CZI,Risk Assessment of Novel Coronavirus COVID-19 Outbreaks Outside China Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China,10.3390/jcm9020571 10.3390/jcm9020575ER -,,,,"We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; and (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number R loc ). We found that in countries with low connectivity to China but with relatively high R loc , the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low R loc benefit the most from policies that further reduce R loc . Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia, and Europe. We investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing. In December 2019, cases of unidentified pneumonia with a history of exposure in the Huanan Seafood Market were reported in Wuhan, Hubei Province. A novel coronavirus, SARS-CoV-2, was identified to be accountable for this disease. Human-to-human transmission is confirmed, and this disease (named COVID-19 by World Health Organization (WHO)) spread rapidly around the country and the world. As of 18 February 2020, the number of confirmed cases had reached 75,199 with 2009 fatalities. The COVID-19 resulted in a much lower case-fatality rate (about 2.67%) among the confirmed cases, compared with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Among the symptom composition of the 45 fatality cases collected from the released official reports, the top four are fever, cough, short of breath, and chest tightness/pain. The major comorbidities of the fatality cases include hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic bronchitis. The source of the virus and the pathogenesis of this disease are still unconfirmed. No specific therapeutic drug has been found. The Chinese Government has initiated a level-1 public health response to prevent the spread of the disease. Meanwhile, it is also crucial to speed up the development of vaccines and drugs for treatment, which will enable us to defeat COVID-19 as soon as possible.",2020,"Boldog, Péter; Tekeli, Tamás; Vizi, Zsolt; Dénes, Attila; Bartha, A. Ferenc; Röst, Gergely; Deng, Sheng-Qun; Peng, Hong-Juan",Journal of Clinical Medicine,3005347918,#1688,
,CZI,Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess Comparative Seasonal Respiratory Virus Epidemic Timing in Utah,10.3390/jcm9030657 10.3390/v12030275,,,,"To understand the time-dependent risk of infection on a cruise ship, the Diamond Princess, I estimated the incidence of infection with novel coronavirus (COVID-19). The epidemic curve of a total of 199 confirmed cases was drawn, classifying individuals into passengers with and without close contact and crew members. A backcalculation method was employed to estimate the incidence of infection. The peak time of infection was seen for the time period from 2 to 4 February 2020, and the incidence has abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 February on which a movement restriction policy was imposed. Without the intervention from 5 February, it was predicted that the cumulative incidence with and without close contact would have been as large as 1373 (95% CI: 570, 2176) and 766 (95% CI: 587, 946) cases, respectively, while these were kept to be 102 and 47 cases, respectively. Based on an analysis of illness onset data on board, the risk of infection among passengers without close contact was considered to be very limited. Movement restriction greatly reduced the number of infections from 5 February onwards. Previous studies have found evidence of viral interference between seasonal respiratory viruses. Using laboratory-confirmed data from a Utah-based healthcare provider, Intermountain Health Care, we analyzed the time-specific patterns of respiratory syncytial virus (RSV), influenza A, influenza B, human metapneumovirus, rhinovirus, and enterovirus circulation from 2004 to 2018, using descriptive methods and wavelet analysis (n = 89,462) on a local level. The results showed that RSV virus dynamics in Utah were the most consistent of any of the viruses studied, and that the other seasonal viruses were generally in synchrony with RSV, except for enterovirus (which mostly occurs late summer to early fall) and influenza A and B during pandemic years.",2020,"Nishiura, Hiroshi; Callahan, Y. Zayne; Smith, K. Trevor; Ingersoll, Celeste; Gardner, Rebecca; Korgenski, K. E.; Sloan, D. Chantel",Journal of Clinical Medicine,2026628614,#2906,
,CZI,Optimization Method for Forecasting Confirmed Cases of COVID-19 in China Prevention Is Better Than the Cure: Risk Management of COVID-19 Synthesis and Bioactivity Assessment of Novel Spiro Pyrazole-Oxindole Congeners Exhibiting Potent and Selective in vitro Anticancer Effects,10.3390/jcm9030674 10.3390/jrfm13030046 10.3390/molecules25051124ER -,,,,"In December 2019, a novel coronavirus, called COVID-19, was discovered in Wuhan, China, and has spread to different cities in China as well as to 24 other countries. The number of confirmed cases is increasing daily and reached 34,598 on 8 February 2020. In the current study, we present a new forecasting model to estimate and forecast the number of confirmed cases of COVID-19 in the upcoming ten days based on the previously confirmed cases recorded in China. The proposed model is an improved adaptive neuro-fuzzy inference system (ANFIS) using an enhanced flower pollination algorithm (FPA) by using the salp swarm algorithm (SSA). In general, SSA is employed to improve FPA to avoid its drawbacks (i.e., getting trapped at the local optima). The main idea of the proposed model, called FPASSA-ANFIS, is to improve the performance of ANFIS by determining the parameters of ANFIS using FPASSA. The FPASSA-ANFIS model is evaluated using the World Health Organization (WHO) official data of the outbreak of the COVID-19 to forecast the confirmed cases of the upcoming ten days. More so, the FPASSA-ANFIS model is compared to several existing models, and it showed better performance in terms of Mean Absolute Percentage Error (MAPE), Root Mean Squared Relative Error (RMSRE), Root Mean Squared Relative Error (RMSRE), coefficient of determination ( R 2 ), and computing time. Furthermore, we tested the proposed model using two different datasets of weekly influenza confirmed cases in two countries, namely the USA and China. The outcomes also showed good performances. A novel coronavirus was reported to the World Health Organization (WHO) in China on 31 December 2019. The WHO named the disease COVID-19 on 11 February 2020. As of 26 February 2020, the disease has been detected on all continents, except for Antarctica. Daily updates on COVID-19 since early February 2020 have made headline news worldwide for much of 2020. This editorial evaluates risk management based on the Global Health Security (GHS) Index of global health security capabilities in 195 countries. The GHS Index lists the countries best prepared for an epidemic or pandemic. COVID-19 is compared with two related coronavirus epidemics, SARS and MERS, in terms of the number of reported human infections, deaths, countries, major country clusters, timelines, and the likelihood of discovering a safe, effective, and approved vaccine. The present work aims to design and synthesize novel series of spiro pyrazole-3,3’-oxindoles analogues and investigate their bioactivity as antioxidant and antimicrobial agents, as well as antiproliferative potency against selected human cancerous cell lines (i.e., breast, MCF-7; colon, HCT-116 and liver, HepG-2) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and proapoptotic protein markers. The analytical and spectral data of the all synthesized target congeners were compatible with their structures. Synthesized compounds showed diverse moderate to powerful antimicrobial and antioxidant activities. Results of MTT assay revealed that seven synthesized compounds (i.e., 11a, 11b, 12a, 12b, 13b, 13c and 13h) particularly exhibited significant cytotoxicity against the three cancerous cell lines under investigation. Ranges of IC50 values obtained were 5.7–21.3 and 5.8–37.4 µg/mL against HCT-116 and MCF-7, respectively; which is 3.8 and 6.5-fold (based on the least IC50 values) more significant relative to the reference chemotherapeutic drug doxorubicin. In HepG-2 cells, the analogue 13h the highest cytotoxicity with IC50 value of 19.2µg/mL relative to doxorubicin (IC50 = 21.6µg/mL). The observed cytotoxicity was specific to cancerous cells, as evidenced by the minimal toxicity in the noncancerous control skin-fibroblast cells. ELISA results indicated that the observed antiproliferative effect against examined cancer cell lines is mediated via engaging the activation of apoptosis as illustrated by the significant increase in proapoptotic protein markers (p53, bax and caspase-3) and reduction in the antiapoptotic marker bcl-2. Taken together, results of the present study emphasize the potential of spiro pyrazole-oxindole analogues as valuable candidate anticancer agents against human cancer cells.",2020,"Al-qaness, A. A. Mohammed; Ewees , A. Ahmed; Fan, Hong; Abd El Aziz , Mohamed; McAleer, Michael; Abo-Salem, M. Heba; Nassrallah, Amr; Soliman, A. F. Ahmed; Ebied, S. Manal; Elawady, E. Mohamed; Abdelhamid, A. Sayeda; El-Sawy, R. Eslam; Al-Sheikh, A. Yazeed; Aboul-Soud, A. M. Mourad",Journal of Clinical Medicine,3006671704,#3465,
,CZI,Risk Management of COVID-19 by Universities in China,10.3390/jrfm13020036,,,,"The rapid spread of new coronaviruses throughout China and the world in 2019–2020 has had a great impact on China’s economic and social development. As the backbone of Chinese society, Chinese universities have made significant contributions to emergency risk management. Such contributions have been made primarily in the following areas: alumni resource collection, medical rescue and emergency management, mental health maintenance, control of staff mobility, and innovation in online education models. Through the support of these methods, Chinese universities have played a positive role in the prevention and control of the epidemic situation. However, they also face the problems of alumni’s economic development difficulties, the risk of deadly infection to medical rescue teams and health workers, infection of teachers and students, and the unsatisfactory application of information technology in resolving the crisis. In response to these risks and emergency problems, we propose some corresponding solutions for public dissemination, including issues related to medical security, emergency research, professional assistance, positive communication, and hierarchical information-based teaching.",2020,"Wang, Chuanyi; Cheng, Zhe; Yue, Xiao-Guang; McAleer, Michael",Journal of Risk and Financial Management,2084356930,#1265,
,CZI,"Risk Management of COVID-19 by Universities in China Short-term Forecasts of the COVID-19 Epidemic in Guangdong and Zhejiang, China: February 13–23, 2020",10.3390/jrfm13020036 ERT - Y - EJOU 10.3390/jcm9020596,,,,"The rapid spread of new coronaviruses throughout China and the world in 2019–2020 has had a great impact on China’s economic and social development. As the backbone of Chinese society, Chinese universities have made significant contributions to emergency risk management. Such contributions have been made primarily in the following areas: alumni resource collection, medical rescue and emergency management, mental health maintenance, control of staff mobility, and innovation in online education models. Through the support of these methods, Chinese universities have played a positive role in the prevention and control of the epidemic situation. However, they also face the problems of alumni’s economic development difficulties, the risk of deadly infection to medical rescue teams and health workers, infection of teachers and students, and the unsatisfactory application of information technology in resolving the crisis. In response to these risks and emergency problems, we propose some corresponding solutions for public dissemination, including issues related to medical security, emergency research, professional assistance, positive communication, and hierarchical information-based teaching. The ongoing COVID-19 epidemic continues to spread within and outside of China, despite several social distancing measures implemented by the Chinese government. Limited epidemiological data are available, and recent changes in case definition and reporting further complicate our understanding of the impact of the epidemic, particularly in the epidemic’s epicenter. Here we use previously validated phenomenological models to generate short-term forecasts of cumulative reported cases in Guangdong and Zhejiang, China. Using daily reported cumulative case data up until 13 February 2020 from the National Health Commission of China, we report 5- and 10-day ahead forecasts of cumulative case reports. Specifically, we generate forecasts using a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model, which have each been previously used to forecast outbreaks due to different infectious diseases. Forecasts from each of the models suggest the outbreaks may be nearing extinction in both Guangdong and Zhejiang; however, the sub-epidemic model predictions also include the potential for further sustained transmission, particularly in Zhejiang. Our 10-day forecasts across the three models predict an additional 65–81 cases (upper bounds: 169–507) in Guangdong and an additional 44–354 (upper bounds: 141–875) cases in Zhejiang by February 23, 2020. In the best-case scenario, current data suggest that transmission in both provinces is slowing down.",2020,"Wang, Chuanyi; Cheng, Zhe; Yue, Xiao-Guang; McAleer, Michael; Roosa, Kimberlyn; Lee, Yiseul; Luo, Ruiyan; Kirpich, Alexander; Rothenberg, Richard; Hyman, M. James; Yan, Ping; Chowell, Gerardo",Journal of Risk and Financial Management,,#1751,
,CZI,Host Factors Affecting Generation of Immunity Against Porcine Epidemic Diarrhea Virus in Pregnant and Lactating Swine and Passive Protection of Neonates,10.3390/pathogens9020130,,,,"Porcine epidemic diarrhea virus (PEDV) is a highly virulent re-emerging enteric coronavirus that causes acute diarrhea, dehydration, and up to 100% mortality in neonatal suckling piglets. Despite this, a safe and effective PEDV vaccine against highly virulent strains is unavailable, making PEDV prevention and control challenging. Lactogenic immunity induced via the gut-mammary gland-secretory IgA (sIgA) axis, remains the most promising and effective way to protect suckling piglets from PEDV. Therefore, a successful PEDV vaccine must induce protective maternal IgA antibodies that passively transfer into colostrum and milk. Identifying variables that influence lymphocyte migration and IgA secretion during gestation and lactation is imperative for designing maternal immunization strategies that generate the highest amount of lactogenic immune protection against PEDV in suckling piglets. Because pregnancy-associated immune alterations influence viral pathogenesis and adaptive immune responses in many different species, a better understanding of host immune responses to PEDV in pregnant swine may translate into improved maternal immunization strategies against enteric pathogens for multiple species. In this review, we discuss the role of host factors during pregnancy on antiviral immunity and their implications for generating protective lactogenic immunity in suckling neonates.",2020,"Langel, Stephanie N.; Wang, Qiuhong; Vlasova, Anastasia N.; Saif, Linda J.",Pathogens,2797271523,#1292,
,CZI,Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks,10.3390/pathogens9030186ER -,,,,"Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in 2012. Currently, the world is concerned about the 2019 novel CoV (SARS-CoV-2) that was initially identified in the city of Wuhan, China in December 2019. Patients presented with severe viral pneumonia and respiratory illness. The number of cases has been mounting since then. As of late February 2020, tens of thousands of cases and several thousand deaths have been reported in China alone, in addition to thousands of cases in other countries. Although the fatality rate of SARS-CoV-2 is currently lower than SARS-CoV, the virus seems to be highly contagious based on the number of infected cases to date. In this review, we discuss structure, genome organization, entry of CoVs into target cells, and provide insights into past and present outbreaks. The future of human CoV outbreaks will not only depend on how the viruses will evolve, but will also depend on how we develop efficient prevention and treatment strategies to deal with this continuous threat.",2020,"Ashour, M. Hossam; Elkhatib, F. Walid; Rahman, M. Md; Elshabrawy, A. Hatem",Pathogens,3006050861,#3521,
,CZI,Chemotherapy strategy for colorectal cancer under the outbreak of novel coronavirus pneumonia,10.3760/cma.j.cn.441530-20200226-00093,,32100980,,"The outbreak of novel coronavirus pneumonia (NCP) makes the medical treatment of colorectal cancers difficult. Cancer patients are more susceptible to infection and tumor history is defined as an important factor of poor prognosis, which challenges both doctors and patients. For metastatic colorectal cancer (CRC) patients, maintenance therapy is the optimal choice. The patients with tumor progression or poor biological behaviorshould receive or or continue combination chemotherapy. Adjuvant chemotherapy should reduce the intensity of treatment and shorten the therapy time. Fever patients during chemotherapy need to receive differential diagnosis and screening according to national standards. Patients with stable diseases and good general conditions may delay imaging examination.. Clinicians should make individual clinical decisions based on the specifics of each patient durding epidemic situation.",2020,"Li, Y. H.; Shen, L.; Li, J.",Zhonghua Wei Chang Wai Ke Za Zhi,1970973591,#2200,
,CZI,Analysis of low positive rate of nucleic acid detection method used for diagnosis of novel coronavirus pneumonia,10.3760/cma.j.cn112137-20200213-00280,,32077662,,,2020,"Wang, C. B.",Zhonghua Yi Xue Za Zhi,1831268804,#1472,
,CZI,[Consideration and suggestions on development of blood transfusion department under the epidemic situation of novel coronavirus pneumonia],10.3760/cma.j.cn112137-20200221-00387,,32108458,,,2020,"Liu, X. M.; Wang, D. Q.",Zhonghua yi xue za zhi,2383858113,#2888,
,CZI,Strengthen comprehensive strategies to treat patients with mild novel coronavirus pneumonia,10.3760/cma.j.cn112138-20200217-00083,,32090534,,,2020,"Jia, W. P.",Zhonghua Nei Ke Za Zhi,3004071935,#1831,
,CZI,Drug interaction monitoring of lopinavir / ritonavir in COVID-19 patients with cancer,10.3760/cma.j.cn112138-20200219-00097,,32114746,,,2020,"Zheng, X. W.; Tao, G.; Zhang, Y. W.; Yang, G. N.; Huang, P.",Zhonghua Nei Ke Za Zhi,1480085725,#3042,
,CZI,[Treatment strategies of Budd-Chiari syndrome during the epidemic period of 2019 coronavirus disease],10.3760/cma.j.cn112139-20200221-00109,,32108459,,"Prevention and control about the situation of 2019 coronavirus disease (COVID-19) are grim at present. In addition to supporting the frontline actively, medical workers in general surgery spare no efforts in making good diagnosis and treatment of specialized diseases by optimizing treatment process, providing medical advice online, mastering indications of delayed operation and emergency operation reasonably, etc. Budd-Chiari syndrome is a complex disorder, and severity of the disease varies, serious cases can be life threatening. While fighting the epidemic, medical workers should also ensure the medical needs of patients. However, instead of continuing the traditional treatment, a new management system should be developed. Based on the characteristics of Budd-Chiari syndrome patients in China and our experience, we divide the patients into ordinary and critical cases, and treatment strategies suitable for the epidemic period of COVID-19 are put forward for reference and discussion by physicians.",2020,"Li, L. H.; Zhang, G.; Dang, X. W.; Li, L.",Zhonghua wai ke za zhi [Chinese journal of surgery],2935897573,#2872,
,CZI,The treatment proposal for the patients with breast diseases in the central epidemic area of 2019 coronavirus disease,10.3760/cma.j.cn112139-20200221-00116,,32096395,,"Currently, the epidemic of 2019 coronavirus disease (COVID-19) is still ongoing. The characteristics including high contagiousness, herd susceptibility and clinical phenotype diversity, made a serious influence on people's daily life and rountine therapy for other diseases. Breast dieases are clinical common diseases. In the central epidemic area of COVID-19, Hubei province, especially Wuhan, the clinical specialists of breast diseases should consider all of the following factors comprehensively: the prevention of COVID-19, the diagnosis and treatment of breast diseases and the accessibility of medical resources. Besides, we should select the appropriate therapy and optimize treatment process so as to prevent the propagation and cross infection of COVID-19 as well as manage the breast diseases without delay. Therefore, we carried out some management proposals of the patients with breast diseases in the central epidemic area during the epidemic of COVID-19 on the basis of conventional treatment guidelines and clinical experiences. The suggestions and corrections from colleagues will be welcomed.",2020,"Zhao, L.; Zhang, L.; Liu, J. W.; Yang, Z. F.; Shen, W. Z.; Li, X. R.",Zhonghua Wai Ke Za Zhi,2130735457,#1890,
,CZI,[Treatment of pancreatic diseases and prevention of infection during outbreak of 2019 coronavirus disease],10.3760/cma.j.cn112139-20200224-00123,,32107909,,"Objective: To explorethe proper protective measures for pancreaticdiseases treatment during theoutbreak of 2019 coronavirus disease(COVID-19). Method: Clinical data of four cases of patients that suffered COVID-19from February 2(nd), 2020 to February 9(th), 2020 in pancreatic surgery were reviewed.After the first patientscuffednosocomial infection of COVID-19, the general protective measures in our department wereupdated.Only one patient was admitted to each room alone, with no more than one caregiver.The body temperature of care givers was measuredtwice a day.Primary protections were applied to all staff.The floor was sterilized using disinfectant with an effective chlorine concentration of 1000 mg/L.The protective measures for interventional procedures were as follow.Primary protection was applied to the operators ofcentral venipuncture catheter, percutaneous abdominal/pleural drainage, percutaneous retroperitoneal drainage, percutaneous transhepatic cholangial drainage and other surgical procedures with local anesthesiaand epidural anesthesia.Secondary protection was applied to the operators of endoscopic retrograde cholangiopancreatography and surgical procedures with general anesthesia. Results: During Feb 2(nd), 2020 to Feb 9(th), 2020, four patients in our department were diagnosed with COVID-19, of which one was died of COVID-19, two were cured, and one is still in hospital for COVID-19.After the update ofprotective measures in our department, no more nosocomial infection of COVID-19occurred.Two central venipuncture catheter, three percutaneous abdominal/pleural drainage, one percutaneous retroperitoneal drainage, one percuteneous transhepatic cholecyst drainage and one open surgery with general anesthesia were performed with no infection of operators. Conclusions: The caregivers of patients are potential infection source of COVID-19.Enhanced protective measures including the management measures of caregivers can decrease the risk of nosocomial infection of COVID-19.",2020,"Gou, S. M.; Yin, T.; Xiong, J. X.; Peng, T.; Li, Y.; Wu, H. S.",Zhonghua wai ke za zhi [Chinese journal of surgery],3004896587,#2819,
,CZI,Clinical analysis of 31 cases of 2019 novel coronavirus infection in children from six provinces (autonomous region) of northern China,10.3760/cma.j.cn112140-20200225-00138,,32118389,,"Objective: To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus(2019-nCoV) infection in children from six provinces (autonomous region) in northern China. Methods: A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces(autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong. Results: The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months -17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted > 3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 9%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate(19%,4/21), procalcitonin(4%,1/28), liver enzyme(22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred. Conclusions: In this case series, 2019-nCoV infections in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis. After general treatment, the short-term prognosis is good.",2020,"Wang, D.; Ju, X. L.; Xie, F.; Lu, Y.; Li, F. Y.; Huang, H. H.; Fang, X. L.; Li, Y. J.; Wang, J. Y.; Yi, B.; Yue, J. X.; Wang, J.; Wang, L. X.; Li, B.; Wang, Y.; Qiu, B. P.; Zhou, Z. Y.; Li, K. L.; Sun, J. H.; Liu, X. G.; Li, G. D.; Wang, Y. J.; Cao, A. H.; Chen, Y. N.",Zhonghua Er Ke Za Zhi,3005477624,#3049,
,CZI,Online learning-related visual impairment and preventive measures during the 2019 novel coronvirus outbreak,10.3760/cma.j.cn112142-20200219-00089,,32077665,,目前我国对2019新型冠状病毒疫情的防治工作正处于关键时期,延迟开学是减少校园内交叉感染、保护儿童和青少年身体健康、共同抗击疫情的重要举措。与此 同时,远程教学模式的大规模开展导致儿童和青少年的学习模式和用眼习惯发生巨大转变,其对儿童和青少年视觉健康的潜在影响不容忽视。本文对线上学习相关眼 健康问题和眼科疾病进行总结,并提出针对性的预防措施,为儿童和青少年在线上学习期间的视功能保护提供有效指导。(中华眼科杂志,2020,56: ).,2020,"Lin, H. T.; Xiang, Y. F.; Cui, T. X.; Chen, J. J.",[Zhonghua yan ke za zhi] Chinese journal of ophthalmology,2123107127,#3772,
,CZI,Precautions in ophthalmic practice in the prevention and control of the novel coronavirus pneumonia epidemic,10.3760/cma.j.cn112142-20200224-00102,,32114748,,,2020,"Wang, N. L.; Jie, Y.; Tao, F. B.",Zhonghua Yan Ke Za Zhi,3004790666,#3048,
,CZI,Emergency management of prevention and control of novel coronavirus pneumonia in departments of stomatology,10.3760/cma.j.cn112144-20200205-00037,,32080994,,"Complying with overall requirements of the government and regulations on public health emergences, as well as the clinical features of diagnosis and treatment of dental illness, this paper refers to previous guidelines and studies on the infection prevention and control in dental diagnosis and treatment in China and foreign countries. Nanjing Stomatological Hospital has implemented the emergency management practices for the prevention and control of novel coronavirus pneumonia (NCP), mainly focusing on the implementation of prevention and control training programs for medical staffs and the infection control projects on the hospital environment. This study could provide reference for rapid response and emergency management for the prevention and control of NCP in the departments of stomatology.",2020,"Tang, H. S.; Yao, Z. Q.; Wang, W. M.",Zhonghua Kou Qiang Yi Xue Za Zhi,3004790666,#1930,
,CZI,Emergency management of prevention and control of novel coronavirus pneumonia in departments of stomatology,10.3760/cma.j.cn112144-20200205-00037,,,,"Complying with overall requirements of the government and regulations on public health emergences, as well as the clinical features of diagnosis and treatment of dental illness, this paper refers to previous guidelines and studies on the infection prevention and control in dental diagnosis and treatment in China and foreign countries. Nanjing Stomatological Hospital has implemented the emergency management practices for the prevention and control of novel coronavirus pneumonia (NCP), mainly focusing on the implementation of prevention and control training programs for medical staffs and the infection control projects on the hospital environment. This study could provide reference for rapid response and emergency management for the prevention and control of NCP in the departments of stomatology.",2020,"TANG, He Shu; YAO, Zhi Qing; WANG, Wen Mei",Chinese Journal of Stomatology,3004790666,#1930,
,CZI,Psychological intervention in oral patients in novel coronavirus pneumonia outbreak period,10.3760/cma.j.cn112144-20200213-00053,,32086886,,"Public health emergencies have an impact on the public mental health. The outbreak of the novel coronavirus has affected the normal diagnosis and treatment services in oral medical institutions across the country. Delay of non-emergency dental service will have a potential impact on the experience, cognition, treatment and rehabilitation of patients with oral diseases. Through literature review, this paper reviewed the oral psychosomatic diseases closely related to patients' psychological state, such as oral mucosal disease, temporomandibular joint disease, bruxism, periodontal disease and so on. It was believed that these patients might be more susceptible to the impact of stress events, and dental specialists should pay more attention to them. At the same time, this paper analyzes the possible psychological stress symptoms of patients with different oral diseases, and puts forward suggestions for remote consultation and emergency treatment of dentists. From the perspective of social role, dentists not only played the role of expert in dental home professional guidance, but also played the role of psychological counseling for patients.",2020,"Qu, X.; Zhou, X. D.",Zhonghua Kou Qiang Yi Xue Za Zhi,1991886054,#1941,
,CZI,Comparison of the clinical characteristics between RNA positive and negative patients clinically diagnosed with 2019 novel coronavirus pneumonia,10.3760/cma.j.cn112147-20200214-00095,,32087623,,"Objective: To raise awareness about 2019 novel coronavirus pneumonia (NCP) and reduce missed diagnosis rate and misdiagnosis rate by comparing the clinical characteristics between RNA positive and negative patients clinically diagnosed with NCP. Methods: From January 2020 to February 2020, 54 patients who were newly diagnosed with NCP in Wuhan Fourth Hospital were included in this study. RT-PCR method was used to measure the level of 2019-nCov RNA in pharyngeal swab samples of these patients. The patients were divided into RNA positive and negative group, and the differences of clinical, laboratory, and radiological characteristics were compared. Results: There were 31 RNA of 2019-nCov positive cases, and 23 negative cases. Common clinical symptoms of two groups were fever (80.64% vs. 86.96%) , chills (61.29% vs.52.17%) , cough (80.64% vs.95.65%) , fatigue (61.30% vs.56.52%) , chest distress (77.42% vs.73.91%) . Some other symptoms were headache, myalgia, dyspnea, diarrhea, nausea and vomiting. The laboratory and radiological characteristics of two groups mainly were lymphopenia, increased erythrocyte sedimentation rate, increased C-reactive protein, increased lactate dehydrogenase, decreased oxygenation index, normal white blood cell count and bilateral chest CT involvement. There was no statistically significant difference in other clinical characteristics except for dyspnea between two groups. Conclusions: RNA positive and negative NCP patients shared similar clinical symptoms, while RNA positive NCP patients tended to have dyspnea. Therefore, we should improve the understanding of NCP to prevent missed diagnosis and misdiagnosis; In addition, more rapid and accurate NCP diagnostic approaches should be further developed.",2020,"Li, Y. Y.; Wang, W. N.; Lei, Y.; Zhang, B.; Yang, J.; Hu, J. W.; Ren, Y. L.; Lu, Q. F.",Zhonghua Jie He He Hu Xi Za Zhi,2620894789,#1580,
,CZI,Novel coronavirus pneumonia (COVID-19) CT distribution and sign features,10.3760/cma.j.cn112147-20200217-00106,,32125131,,"Objective: To investigate the imaging findings of 2019 novel coronavirus pneumonia (COVID-19). Methods: From January 20 to February 5, 2020, a total of 130 patients diagnosed with COVID-19 from seven hospitals in China were collected. The imaging data were reviewed and analyzed in detail. Results: (1) Distribution: the lesion detected in the lung unilaterally in 14 cases (10.7%) and bilaterally in 116 cases (89.3%). According to the distribution in the lobes of the lung, all cases could be classified into subpleural distribution (102 cases, 78.4%), centrilobular distribution (99 cases, 76.1%) and diffused distribution (8 cases, 6.1%). (2) Number of lesions: single lesion 9 cases (6.9%); multiple lesions 113 cases (86.9%), diffuse lesions 8 cases (6.1%). (3) Imaging density: 70 cases (53.8%) of ground-glass opacity (GGO), 60 cases (46.2%) of GGO + consolidation. (4) Accompanying signs: 100 cases (76.9%) with vascular thickening, 98 cases (75.3%) with ""pleural parallel sign"" ; ""intralobular septal thickening"" in 100 cases (76.9%); ""halo sign"" in 13 cases (10%); ""reversed-halo sign"" in 6 cases (4.6%); pleural effusion in 3 cases (2.3 %), and pneumatocele in 2 cases (1.5%); no case with pulmonary cavity. Among 35 patients that underwent follow-up CT, 21 patients (60%) improved while 14 (40%) exacerbated. Conclusions: COVID-19 imaging characteristic mainly has subpleural, centrilobular and diffused distribution. The first two distributions can overlap or progress to diffused distribution. In the later period, it was mainly manifested as organizing pneumonia and fibrosis. The most valuable characteristic is the pleural parallel sign.",2020,"Wu, J.; Feng, C. L.; Xian, X. Y.; Qiang, J.; Zhang, J.; Mao, Q. X.; Kong, S. F.; Chen, Y. C.; Pan, J. P.",Zhonghua Jie He He Hu Xi Za Zhi,3006643024,#3276,
,CZI,Expert recommendations on the management of patients with advanced non-small cell lung cancer during epidemic of COVID-19 (Trial version),10.3760/cma.j.cn112147-20200221-00138,,32125132,,"The outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency of major international concern. Given the systemic immunosuppressive state caused by malignancy and anticancer treatments, patients with advanced lung cancer may be at a higher risk of COVID-19 infection. During epidemic of COVID-19, a guideline for the optimal management of patients with advanced lung cancer urgently needs to be proposed to distinguish the symptoms of COVID-19 and the side effects of antitumor drugs. This network questionnaire survey was conducted on the lung cancer group of the Chinese Thoracic Society, Chinese Medical Association; the lung cancer group of the Chinese Society of Clinical Oncology Youth Committee; and the Chinese Respiratory Oncology Collaboration. 321 valid questionnaires were received. Based on the guidelines on lung cancer and the results of the questionnaires, a consensus was reached. During the epidemic of COVID-19, We recommended that patients with advanced NSCLC should be treated as outpatients as possible at the nearest medical center; Patients who need to be hospitalized for antitumor treatment should be excluded from COVID-19 infection; More intensive attention should be paid to identification of COVID-19-related symptoms and adverse reactions caused by the malignancy or antitumor treatments. Stronger personal protection should be made for advanced NSCLC patients; An intentional postponing of antitumor treatment should be considered according to patient performance status. Treatment strategies should be made according to different types of advanced NSCLC patients and efficacy and toxicity of drugs.",2020,"Lung Cancer Study Group, Chinese Thoracic Society Chinese Medical Association; Chinese Respiratory Oncology, Collaboration",Zhonghua Jie He He Hu Xi Za Zhi,2059561156,#3339,
,CZI,Epidemiological characteristics of novel coronavirus pneumonia in Henan,10.3760/cma.j.cn112147-20200222-00148,,32118390,,"Objective: To study the epidemiological characteristics of COVID-19 in Henan Province. Methods: An epidemiological study was conducted based on the latest epidemic information of 1,265 confirmed cases (including regional distribution, severe illness, and deaths) announced by Health Commission of Henan Province, as well as the details of 1,079 COVID-19 officially released by Health Commission of municipalities in Henan Province collected as of 24:00 on February 19, 2020. Results: Among 1 079 patients diagnosed with COVID-19, there were 573 male (53.2%) and 505 female (46.8%) , with the ratio of male to female of 1.14:1; The majority of patients were 36-59 years old (553 cases, 51.3%) , and the mean age was 46 (interquartile range is 24) years old; 515 cases (47.7%) had a history of living, traveling, doing business in Wuhan or a brief stopover at Wuhan train stop, and 382 (35.4%) had a history of close contact with confirmed patients; There were 72 severe cases (5.7%) in 1 265 patients, and the fatality rate was 1.5%. A high number of cases were reported in Xinyang (269 cases, 21.26%) , Zhengzhou (156 cases, 12.33%) , Nanyang (155 cases, 12.25%) , Zhumadian (139 cases, 10.99%) , followed by Shangqiu (91 cases, 7.19%) , Zhoukou (76 cases, 6.01%) . Among 605 patients, the symptoms were fever (553 cases, 91.4%) , debilitation (44 cases, 7.3%) , cough (110 cases, 18.2%) , expectoration (19 cases, 3.1%) , chills (6 cases, 1.0%) , shiver (7 cases, 1.2%) , running nose (21 cases, 3.5%) , stuffy noses (8 cases, 1.3%) , throat dryness and sore (24 cases, 4.0%) , headache (21 cases, 3.5%) , chest pain (6 cases, 1.0%) , anhelation (18 cases, 3.0%) , and gastrointestinal symptom (21 cases, 3.5%) . The age of deaths ranged from 33 to 86 years old, with an average age of 72 (interquartile range of 17) years old; there be 7 males (63.6%) and 4 females (36.4%) . Conclusion: The cases in Henan Province were mainly imported cases and had certain geographical location relevance; meanwhile, there was a family-focused incidence. The overall trend of new cases was wave-like decline, and the number of deaths was high among elderly men with underlying diseases.",2020,"Cheng, J. L.; Huang, C.; Zhang, G. J.; Liu, D. W.; Li, P.; Lu, C. Y.; Li, J.",Zhonghua Jie He He Hu Xi Za Zhi,3005079553,#3067,
,CZI,The keypoints in treatment of the critical novel coronavirus pneumonia patient,10.3760/cma.j.cn112147-20200222-00151,,32087621,,"The novel coronavirus pneumonia (new coronavirus pneumonia) (NCP) has been prevalent in Wuhan and spread rapidly to all of our country. Some cases can develop into ARDS, or even death. We will share the treatment experience of severe NCP with the first-line treatment experience. The best respiratory support mode should be selected, but the timing of intubation and protection during intubation are two difficulties; patients with high level peep and poor effect in prone position can be given ECMO support. For NCP patients with mechanical ventilation, reasonable sedation and analgesia strategies should be formulated; delirium should not be ignored. In addition, there is up regulation of inflammatory factors in patients with severe NCP, but the effect of renal replacement therapy needs to be further confirmed by clinical research.",2020,"Qiu, H. B.; Li, X. Y.; Du, B.; Kang, H. Y. J.; Wang, Y. S.; Wang, F.; Sun, B.; Tong, Z. H.",Zhonghua Jie He He Hu Xi Za Zhi,3003464757,#1515,
,CZI,[Analysis of bronchoscope-guided tracheal intubation in 12 cases with COVID-19 under the personal protective equipment with positive pressure protective hood],10.3760/cma.j.cn112147-20200222-00153,,32133829,,"Endotracheal intubation is an independent risk factor for respiratory infectious diseases. We conducted a retrospective study in 12 cases with COVID-19 who underwent endotracheal intubation at ICU of the Guangzhou eighth hospital from January 20 to February 10, 2020. The intubation procedure, anesthetic regimen, and complication were collected and analyzed. The 9 healthcare workers who involved in intubation received virus nucleic acid test and 14 days temperature monitoring. All 12 patients were successfully intubated under the guidance of bronchoscope, without any complications. Midazolam, Propofol and Morphine or fentanyl were used for sedation and analgesia, avoiding patients cough and agitated during the procedure. The 9 healthcare workers were protected under the Personal Protective Equipment(PPE) with positive pressure protective hood. The detection of oropharyngeal swab virus nucleic acid were negative in all 9 healthcare workers, none of them had fever or any respiratory symptoms. The PPE with positive pressure protective hood should be needed to perform bronchoscope-guided endotracheal intubation in patients with COVID-19, it could strengthen to protect healthcare workers from virus exposure.",2020,"Cai, S. J.; Wu, L. L.; Chen, D. F.; Li, Y. X.; Liu, Y. J.; Fan, Y. Q.; Du, S. H.; Huang, H.; Liu, N.; Cheng, L. L.; Deng, X. L.; Li, S. Y.",Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases,627918116,#5083,
,CZI,[The keypoints in treatment of the critical coronavirus disease 2019 patient],10.3760/cma.j.cn112147-20200224-00159,,32111113,,"The treatment of critically ill patients with coronavirus disease 2019(COVID-19) faces compelling challenges. In this issue, we'd like to share our first-line treatment experience in treating COVID-19. Hemodynamics need be closely monitored and different types of shock should be distinguished. Vasoconstrictor drugs should be used rationally and alerting of complications is of the same importance. The risk of venous thromboembolism (VTE) needs to be assessed, and effective prevention should be carried out for high-risk patients. It is necessary to consider the possibility of pulmonary thromboembolism (PTE) in patients with sudden onset of oxygenation deterioration, respiratory distress, reduced blood pressure. However, comprehensive analysis of disease state should be taken into the interpretation of abnormally elevated D-Dimer. Nutritional support is the basis of treatment. It's important to establish individual therapy regimens and to evaluate, monitor and adjust dynamically. Under the current epidemic situation, convalescent plasma can only be used empirically, indications need to be strictly screened, the blood transfusion process should be closely monitored and the curative effect should be dynamically evaluated.",2020,"Li, X. Y.; Du, B.; Wang, Y. S.; Kang, H. Y. J.; Wang, F.; Sun, B.; Qiu, H. B.; Tong, Z. H.",Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases,2990072816,#2875,
,CZI,Expert consensus on Pulmonary Function Testing during the epidemic of Corona Virus Disease 2019,10.3760/cma.j.cn112147-20200225-00175,,32129580,,"Corona virus disease 2019 (COVID-19) is mainly transmitted by respiratory droplets and close contact. Pulmonary function testing procedures have been associated with an increasing risk of COVID-19 transmission among patients/subjects and medical staffs. Effective prevention and control strategies must be compulsorily implemented to prevent nosocomial infection. This recommendation is intended to be followed by healthcare workers (HCWs) of pulmonary function testing laboratory when COVID-19 is in epidemic. Based on the features of pulmonary function testing, precaution principles and strategies are developed in three aspects of management for HCWs, operating procedure, environment and equipment. Indications of pulmonary function testing should be followed strictly. It is strongly recommended to suspend the test for the confirmed or suspected cases of COVID-19 during the contagious stage, and to postpone the test for other patients if it is not imperative. Medical personnel should mandatorily adhere to the standard stratification of precaution measures. Patients/Subjects should be isolated in a separate area for testing. Disposable in-line filters must be used during pulmonary function testing. Cleaning and disinfection procedures for environment and equipment in pulmonary function testing laboratory should be paid more attention. 新型冠状病毒肺炎(COVID-19)主要通过呼吸道飞沫传播及密切接触传播。肺功能检查可增加医务人员和受检者发生COVID-19传播的风险,必须严 格执行有效的预防和控制措施以防止院内感染。为了指导肺功能检查室医务人员做好防控工作,本指引结合肺功能检查的特点,制订了当前疫情下肺功能检查在医务 人员管理、检查流程管理和检查环境物品管理3个方面的要求及注意事项。主要强调在疫情流行期间,必须严格掌握肺功能检查的适应证,强烈建议COVID-1 9确诊病例或疑似病例在传染期内暂缓检查,其他病患如非病情急需也暂缓检查;肺功能室医务人员应严格执行标准分级防护措施;受试者应在单独区域进行隔离检 查;检查时必须使用一次性呼吸过滤器;并重视肺功能检查环境和设备的清洁消毒。.",2020,"Task Force of Pulmonary Function, Testing; Clinical, Respiratory; Physiology, Chinese Association of Chest Physicians; Pulmonary Function Testing Group, Respiratory Therapeutics Group; Chinese Thoracic, Society",Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases,2326597313,#5440,
,CZI,"What are the highlights of ""Diagnosis and treatment of Disease 2019 novel coronavirus infection suitable for Military support Hubei medical team""",10.3760/cma.j.cn112147-20200225-00183,,32098466,,"Thousands of medical workers in the Military support Hubei medical team are exerting themselves in many hospitals in Hubei Province. They are diligent in treating patients, at the same time, they constantly summarize experience and combine the characteristics of military hospitals. According to "" the Diagnosis and Treatment of New Coronavirus Pneumonia ""(6th edition) of the National Health Commission of the People's Republic of China, a new guideline for the diagnosis and treatment of 2019 novel coronavirus infection suitable for the military (first trial version) was established. Some unique opinions and suggestions are put forward in terms of disease name, diagnosis criteria, antiviral treatment, glucocorticoid application, etc. This article will make a proper interpretation in order to understand the guideline better and help guide the diagnosis and treatment of diseases.",2020,"Shi, Y.",Zhonghua Jie He He Hu Xi Za Zhi,3005489812,#2403,
,CZI,Recommendations for respiratory rehabilitation of COVID-19 in adult,10.3760/cma.j.cn112147-20200228-00206,,32125127,,"COVID-19 is a highly infectious respiratory infection disease, which leads to dysfunction of respiratory, physical, and psychological of the patients. pulmonary rehabilitation is an important intervention for clinical patients as well as cure patients. With the deeper cognition of COVID-19 and accumulation of clinical experience, we proposed the recommendations for pulmonary rehabilitation of COVID-19 in adults based on the opinions of front-line clinical experts involved in the management of this epidemic and a review of the relevant literature and evidences: 1. for the inpatients with COVID-19, pulmonary rehabilitation would relieve the symptoms of dyspnea, anxiety, and depression; eventually improve physical function and the quality of life; 2. For severe/critical inpatients, the early performance of pulmonary rehabilitation is not suggested. 3. For isolating patients, the pulmonary rehabilitation guidence should be conducted through education video, instruction manual or remote consultation. 4. Assessment and monitor should be performed throughout the entire pulmonary rehabilitation process.5. Taking proper grading protection following the guideline. These recommendations can serve as a clinical practice guidence and basis for pulmonary rehabilitation of COVID-19.",2020,"Chinese Association of Rehabilitation, Medicine; Respiratory rehabilitation committee of Chinese Association of Rehabilitation, Medicine; Cardiopulmonary rehabilitation Group of Chinese Society of Physicai, Medicine; Rehabilitation",Zhonghua Jie He He Hu Xi Za Zhi,2354723963,#3433,
,CZI,"Cause analysis and treatment strategies of ""recurrence"" with novel coronavirus pneumonia (covid-19) patients after discharge from hospital",10.3760/cma.j.cn112147-20200229-00219,,32118391,,"With a large number of COVID-19 patients discharging from hospital, some had showed re-fever and positive nucleic acid test after discharge from hospital. This might be due to the biological characteristics of 2019-nCoV, and might also be related to the basic disease, clinical status, glucocorticoid using, sample sampling, processing and detecting of patients, and some even related to the re-infection or secondary bacterial virus infection. Therefore, we suggest that in view of this phenomenon, further stratified management of discharge from hospital should be carried out on the basis of guidelines, especially for patients with advanced age, underlying diseases or severe or critical pneumonia. For those patients who can't completely deoxygenate for a long time after hospitalization, individualized treatment methods and different discharge evaluation criteria should be adopted to ensure the complete cure of patients and prevent recurrencing after discharge from hospital. 随着新型冠状病毒肺炎(COVID-19)患者大量出院,部分患者出院后出现再次发热、核酸检测阳性的现象。这可能是由于新型冠状病毒(2019-nCo V)的生物学特性所决定的,也可能与患者的基础疾病、临床状况、糖皮质激素的使用以及标本采样、处理、检测有关,甚至还与部分患者再次感染或继发其他细菌 病毒感染有关。为此,我们建议针对这一现象,应在指南基础上进一步对患者出院进行分层管理,尤其是高龄、有基础疾病或重症及危重型患者可能要进行相应处理 措施,对于患者住院后长期吸氧难以完全脱氧者采用个体化的处理方式和不同出院评估标准,旨在保证彻底治愈患者,防止出院后""复发""。.",2020,"Zhou, L.; Liu, K.; Liu, H. G.",Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases,2041150026,#4323,
,CZI,Comparison of heart failure and 2019 novel coronavirus pneumonia in chest CT features and clinical characteristics,10.3760/cma.j.cn112148-20200218-00093,,32129583,,"Objective: To identify the characteristics including clinical features and pulmonary computed tomography (CT) features of heart failure and novel coronavirus pneumonia(COVID-19). Methods: This study was a retrospective study. A total of 7 patients with Heart failure and 12 patients with COVID-19 in the Second Xiangya Hospital of Central South University between December 1, 2019 and February 15, 2020 were enrolled. The baseline clinical and imaging features of the two groups were statistically analyzed. Results: There was no significant difference in age and sex between the two groups, but the incidence of epidemiological contact history, fever or respiratory symptoms in the COVID-19 group was significantly higher than that in the heart failure group (12/12 vs. 2/7, P=0.001; 12/12 vs. 4/7, P<0.001). While the proportion of cardiovascular diseases and impaired cardiac function was significantly less than that of the heart failure group(2/12 vs.7/7, P<0.001; 0/12 vs.7/7, P<0.001). For imaging features, both groups had ground-glass opacity and thickening of interlobular septum, but the ratio of central and gradient distribution was higher in patients with heart failure than that in patients with COVID-19 (4/7 vs. 1/12, P=0.04). In heart failure group, the ratio of the expansion of small pulmonary veins was also higher (3/7 vs. 0, P=0.013), and the lung lesions can be significantly improved after effective anti-heart failure treatment. Besides, there are more disease with rounded morphology in COVID-19 (9/12 vs. 2/7, P=0.048) . Conclusions: More patients with COVID-19 have epidemiological history and fever or respiratory symptoms. There are significant differences in chest CT features, such as enlargement of pulmonary veins, lesions distribution and morphology between heart failure and COVID-19.",2020,"Zhu, Z. W.; Tang, J. J.; Chai, X. P.; Fang, Z. F.; Liu, Q. M.; Hu, X. Q.; Xu, D. Y.; Tang, L.; Tai, S.; Wu, Y. Z.; Zhou, S. H.",Zhonghua Xin Xue Guan Bing Za Zhi,3006328792,#4358,
,CZI,Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV,10.3760/cma.j.cn112148-20200220-00105,,32120458,,"Objective: To explore the clinical characteristics and prognosis of the new coronavirus 2019-nCoV patients combined with cardiovascular disease (CVD). Methods: A retrospective analysis was performed on 112 COVID-19 patients with CVD admitted to the western district of Union Hospital in Wuhan, from January 20, 2020 to February 15, 2020. They were divided into critical group (ICU, n=16) and general group (n=96) according to the severity of the disease and patients were followed up to the clinical endpoint. The observation indicators included total blood count, C-reactive protein (CRP), arterial blood gas analysis, myocardial injury markers, coagulation function, liver and kidney function, electrolyte, procalcitonin (PCT), B-type natriuretic peptide (BNP), blood lipid, pulmonary CT and pathogen detection. Results: Compared with the general group, the lymphocyte count (0.74×10(9) (0.34×10(9), 0.94×10(9))/L vs. 0.99×10(9) (0.71×10(9), 1.29×10(9))/L, P=0.03) was extremely lower in the critical group, CRP (106.98 (81.57, 135.76) mg/L vs. 34.34 (9.55,76.54) mg/L, P<0.001) and PCT (0.20 (0.15,0.48) μg/L vs. 0.11 (0.06,0.20)μg/L, P<0.001) were significantly higher in the critical group. The BMI of the critical group was significantly higher than that of the general group (25.5 (23.0, 27.5) kg/m(2) vs. 22.0 (20.0, 24.0) kg/m(2), P=0.003). Patients were further divided into non-survivor group (17, 15.18%) group and survivor group (95, 84.82%). Among the non-survivors, there were 88.24% (15/17) patients with BMI> 25 kg/m(2), which was significantly higher than that of survivors (18.95% (18/95), P<0.001). Compared with the survived patients, oxygenation index (130 (102, 415) vs. 434 (410, 444), P<0.001) was significantly lower and lactic acid (1.70 (1.30, 3.00) mmol/L vs. 1.20 (1.10, 1.60) mmol/L, P<0.001) was significantly higher in the non-survivors. There was no significant difference in the proportion of ACEI/ARB medication between the critical group and the general group or between non-survivors and survivors (all P>0.05). Conclusion: COVID-19 patients combined with CVD are associated with a higher risk of mortality. Critical patients are characterized with lower lymphocyte counts. Higher BMI are more often seen in critical patients and non-survivor. ACEI/ARB use does not affect the morbidity and mortality of COVID-19 combined with CVD. Aggravating causes of death include fulminant inflammation, lactic acid accumulation and thrombotic events.",2020,"Peng, Y. D.; Meng, K.; Guan, H. Q.; Leng, L.; Zhu, R. R.; Wang, B. Y.; He, M. A.; Cheng, L. X.; Huang, K.; Zeng, Q. T.",Zhonghua Xin Xue Guan Bing Za Zhi,2965860541,#3321,
,CZI,[Analysis of myocardial injury in patients with COVID-19 and association between concomitant cardiovascular diseases and severity of COVID-19],10.3760/cma.j.cn112148-20200225-00123,,32141280,,"Objective: To evaluate the cardiovascular damage of patients with COVID-19, and determine the correlation of serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (cTnI) with the severity of COVID-19, and the impact of concomitant cardiovascular disease on severity of COVID-19 was also evaluated. Methods: A cross-sectional study was designed on 150 consecutive patients with COVID-19 in the fever clinic of Tongji Hospital in Wuhan from January to February in 2020, including 126 mild cases and 24 cases in critical care. Both univariate and multivariate logistic regression were used to analyze the correlation of past medical history including hypertension, diabetes and coronary heart disease (CHD) , as well as the levels of serum NT-proBNP and cTnI to the disease severity of COVID-19 patients. Results: Age, hypersensitive C-reactive protein(hs-CRP) and serum creatinine levels of the patients were higher in critical care cases than in mild cases(all P<0.05). Prevalence of male, elevated NT-proBNP and cTnI, hypertension and coronary heart disease were significantly higher in critical cases care patients than in the mild cases(all P<0.05). Univariate logistic regression analysis showed that age, male, elevated NT-proBNP, elevated cTnI, elevated hs-CRP, elevated serum creatinine, hypertension, and CHD were significantly correlated with critical disease status(all P<0.05). Multivariate logistic regression analysis showed that elevated cTnI(OR=26.909, 95%CI 4.086-177.226, P=0.001) and CHD (OR=16.609, 95%CI 2.288-120.577, P=0.005) were the independent risk factors of critical disease status. Conclusions: COVID-19 can significantly affect the heart function and lead to myocardial injury. The past medical history of CHD and increased level of cTnI are two independent determinants of clinical disease status in patients with COVID-19.",2020,"Chen, C.; Yan, J. T.; Zhou, N.; Zhao, J. P.; Wang, D. W.",Zhonghua xin xue guan bing za zhi,2913916509,#5104,
,CZI,Health protection guideline of mobile cabin hospitals during Novel Coronavirus Pneumonia (NPC) outbreak,10.3760/cma.j.cn112150-20200217-00121,,32072919,,"This guideline is applicable to the health protection requirements of large indoor stadiums which are reconstructed as treatment sites for the Novel Coronavirus Pneumonia (NPC) patients with mild symptoms during the outbreak. Focusing on the health emergency scenario of severe virus infectious diseases and atypical places where NPC patients with mild symptom gather, from perspectives of functional zones, hygiene facilities, personal protection, and management system, health risk protection recommendations and countermeasures are comprehensively proposed to mainly protect staffs and surrounding environment. The implementation of this guideline will provide technique support for emergency requirements of indoor stadiums reconstructed as mobile cabin hospitals.",2020,"Novel Coronavirus Pneumonia Emergency Response Key Places, Protection; Disinfection Technology Team, Chinese Center for Disease Control; Prevention",Zhonghua Yu Fang Yi Xue Za Zhi,1992330641,#1277,
,CZI,Health protection guideline of passenger transport stations and transportation facilities during novel coronavirus pneumonia (NCP) outbreak,10.3760/cma.j.cn112150-20200217-00130,,32072920,,"During the coronavirus pneumonia (NCP) outbreak, the transportation industries are faced with the more burdensome tasks of outbreak prevention and control as well as ensuring smooth transportation. It is important to organize transportation in order to restore the order of production and life, ensure the normal economic and social operation, and control the outbreak in the whole society. From the perspective of health, this guideline puts forward technical requirements on the operation management, personnel requirements and health protection of passenger transportation places such as aviation, railway, subway, bus, taxi, ship, etc., which reduces the impact of the NCP outbreak on the transportation industry and personal health risks.",2020,"Novel Coronavirus Pneumonia Emergency Response Key Places, Protection; Disinfection Technology Team, Chinese Center for Disease Control; Prevention",Zhonghua Yu Fang Yi Xue Za Zhi,2509882129,#1278,
,CZI,Technologies and requirements of protection and disinfection in key places during the novel coronavirus pneumonia (NCP) outbreak,10.3760/cma.j.cn112150-20200217-00131,,32077664,,"Novel coronavirus pneumonia (NCP), a new respiratory infectious disease, has become an important public health problem. Inappropriate protection and disinfection measures are potential risk factors of transmission and outbreak of NCP in key places. This theme issue is concerned with the prevention and control of NCP. Comprehensive measures and suggestions for protection and disinfection are put forward from perspectives of functional areas in key places, such as hotels, mobile cabin hospitals, passenger transport stations and public transport facilities, environment and facilities, personal protection, operation management system, etc., so as to provide technical support for the prevention and control of new respiratory infectious diseases.",2020,"Novel Coronavirus Pneumonia Emergency Response Key Places, Protection; Disinfection Technology Team, Chinese Center for Disease Control; Prevention",Zhonghua Yu Fang Yi Xue Za Zhi,2166798197,#1537,
,CZI,Risk assessment of exported risk of novel coronavirus pneumonia from Hubei Province,10.3760/cma.j.cn112150-20200219-00142,,32083409,,"Objective: To evaluate the exported risk of novel coronavirus pneumonia (NCP) from Hubei Province and the imported risk in various provinces across China. Methods: Data of reported NCP cases and Baidu Migration Indexin all provinces of the country as of February 14, 2020 were collected. The correlation analysis between cumulative number of reported cases and the migration index from Hubei was performed, and the imported risks from Hubei to different provinces across China were further evaluated. Results: A total of 49 970 confirmed cases were reported nationwide, of which 37 884 were in Hubei Province. The average daily migration index from Hubei to other provinces was 312.09, Wuhan and other cities in Hubei were 117.95 and 194.16, respectively. The cumulative NCP cases of provinces was positively correlated with the migration index derived from Hubei province, also in Wuhan and other cities in Hubei, with correlation coefficients of 0.84, 0.84, and 0.81. In linear model, population migration from Hubei Province, Wuhan and other cities in Hubei account for 71.2%, 70.1%, and 66.3% of the variation, respectively. The period of high exported risk from Hubei occurred before January 27, of which the risks before January 23 mainly came from Wuhan, and then mainly from other cities in Hubei. Hunan Province, Henan Province and Guangdong Province ranked the top three in terms of cumulative imported risk (the cumulative risk indices were 58.61, 54.75 and 49.62 respectively). Conclusion: The epidemic in each province was mainly caused by the importation of Hubei Province. Taking measures such as restricting the migration of population in Hubei Province and strengthening quarantine measures for immigrants from Hubei Province may greatly reduce the risk of continued spread of the epidemic.",2020,"Hu, J. X.; He, G. H.; Liu, T.; Xiao, J. P.; Rong, Z. H.; Guo, L. C.; Zeng, W. L.; Zhu, Z. H.; Gong, D. X.; Yin, L. H.; Wan, D. H.; Zeng, L. L.; Ma, W. J.",Zhonghua Yu Fang Yi Xue Za Zhi,3003596834,#1627,
,CZI,[The importance of strengthening the ability of fundamental disease prevention and control system from the perspective of the epidemic situation of COVID-19],10.3760/cma.j.cn112150-20200220-00149,,32107911,,"COVID-19 has been in epidemic for nearly two months. The prevention and control measures have achieved remarkable results. From the response and disposal process of this epidemic, it is exposed that fundamental disease prevention and control system are insufficient in human resources and ability of laboratory testing. It is suggested that the disease control institutions should strengthen the construction of these aspects in future.",2020,"Wang, M.",Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine],2366762302,#2968,
,CZI,[Analysis on epidemic situation and spatiotemporal changes of COVID-19 in Anhui],10.3760/cma.j.cn112150-20200221-00150,,32107910,,"We used the epidemic data of COVID-19 published on the official website of the municipal health commission in Anhui province. We mapped the spatiotemporal changes of confirmed cases, fitted the epidemic situation by the population growth curve at different stages and took statistical description and analysis of the epidemic situation in Anhui province. It was found that the cumulative incidence of COVID-19 was 156/100 000 by February 18, 2020 and the trend of COVID-19 epidemic declined after February 7, changing from J curve to S curve. The actual number of new cases began to decrease from February 2 to February 4 due to the time of case report and actual onset delayed by 3 to 5 days.",2020,"Liu, M.; Xu, H. L.; Yuan, M.; Liu, Z. R.; Wu, X. Y.; Zhang, Y.; Ma, L. Y.; Gong, L.; Gan, H.; Zong, W. W.; Tao, S. M.; Liu, Q.; Du, Y. N.; Tao, F. B.",Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine],3006643024,#2886,
,CZI,Thoughts and suggestions on modern construction of disease prevention and control system,10.3760/cma.j.cn112150-20200221-00151,,32100978,,"The critical period for the prevention and control of novel coronavirus pneumonia (NCP) in China, in response to requirements for accelerating the modernization of the disease prevention and control system, we analyzed and summarized the current situation, existing problems, and deficiencies in China's modernization of disease prevention and control system. In addition, we put forward the contents and countermeasures for the modernization of the disease prevention and control system. The modernization of the disease prevention and control system should be built around governance modernization, talent modernization, equipment modernization, scientific research modernization, and modernization of the regulatory system. The countermeasures and suggestions need to reposition the disease prevention and control system, rationalize the management system and operating mechanism, strengthen the modernization of talents and equipment, strengthen scientific research on disease prevention and control, and further improve the disease prevention and control legal system.",2020,"Cheng, J. Q.",Zhonghua Yu Fang Yi Xue Za Zhi,2387214729,#2327,
,CZI,Epidemic trend of corona virus disease 2019 (COVID-19) in mainland China,10.3760/cma.j.cn112150-20200222-00163,,32125133,,"Objective: In order to master the epidemic trend of corona virus disease 2019 (COVID-19) and evaluate the effect of prevention and control, we evaluate the epidemic dynamics of COVID-19 in mainland China, Hubei province, Wuhan city and other provinces outside Hubei from January 16 to February 14, 2020. Methods: We collected the daily number of new confirmed COVID-19 cases by nucleic acid detection reported by the National Health Commission from January 16, 2020 to February 14, 2020. The analysis includes the epidemic curve of the new confirmed cases, multiple of the new confirmed cases for period-over-period, multiple of the new confirmed cases for fixed-base, and the period-over-period growth rate of the new confirmed cases. Results: From January 16 to February 14, 2020, the cumulative number of new confirmed cases of COVID-19 in mainland China was 50 031, including 37 930 in Hubei province, 22 883 in Wuhan city and 12 101 in other provinces outside Hubei. The peak of the number of new confirmed cases in other provinces outside Hubei was from January 31 to February 4, 2020, and the peak of new confirmed cases in Wuhan city and Hubei province was from February 5 to February 9, 2020. The number of new confirmed cases in other provinces outside Hubei showed a significant decline (23% compared with the peak) from February 5 to February 9, 2020, while the number of new confirmed cases in Wuhan city (30% compared with the peak) and Hubei Province (37% compared with the peak) decreased significantly from February 10 to February 14, 2020. Conclusion: The epidemic prevention and control measures taken by the state and governments at all levels have shown very significant effects, effectively curbing the spread of the COVID-19 epidemic in China.",2020,"Zhu, Z. B.; Zhong, C. K.; Zhang, K. X.; Dong, C.; Peng, H.; Xu, T.; Wang, A. L.; Guo, Z. R.; Zhang, Y. H.",Zhonghua Yu Fang Yi Xue Za Zhi,3006645647,#3231,
,CZI,Analysis on the epidemic factors for the Corona Virus Disease,10.3760/cma.j.cn112150-20200227-00196,,32125129,,"Since December 2019, corona virus disease 2019 (COVID-19) , an emerging infection disease occurred in Wuhan, has spread in the mainland China. The epidemic factors on the basis of knowledge of SARS-CoV-2 were discussed in this paper. This puts a lot of pressure on clinical resources and care. SARS-CoV-2 is a novel corona virus, the onset of COVID-19 is slow, and the pathogenesis of SARS-CoV-2 remains unclear and may lead to multiple organ damage. These put a lot of pressure on clinical resources and care. Source of infection including the patients, asymptomatic carrier and patients in the incubation period are contagious. It is difficult to control source of infection. Routes of SARS-CoV-2 transmission are diversified and the main routes of transmission for COVID-19 are droplet transmission and close contact transmission. All population have susceptibility to SARS-CoV-2. Social factors such population movements and aggregation accelerated the spread of SARS-CoV-2. The Chinese government's adopted measures are positive and effective, and are accepted by the expert group from the World Health Organization. However, it will be a long-term hard work in the future to seriously summarize and think deeply to achieve public health security in China.",2020,"Yang, H. Y.; Duan, G. C.",Zhonghua Yu Fang Yi Xue Za Zhi,2002726211,#3262,
,CZI,Pregnant women with new coronavirus infection: a clinical characteristics and placental pathological analysis of three cases,10.3760/cma.j.cn112151-20200225-00138,,32114744,,"Objective: To investigate the clinical characteristics and placental pathology of 2019-nCoV infection in pregnancy, and to evaluate intrauterine vertical transmission potential of 2019-nCoV infection. Methods: The placentas delivered from pregnant women with confirmed 2019-nCoV infection which were received in the Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology collected by February 4th, 2020 and retrospectively studied. Their clinical material including placental tissue and lung CT, and laboratory results were collected, meanwhile, nucleic acid detection of 2019-nCoV of the placentas were performed by RT-PCR. Results: Three placentas delivered from pregnant women with confirmed 2019-nCoV infection, who were all in their third trimester with emergency caesarean section. All of the three patients presented with fever (one before caesarean and two in postpartum), and had no significant leukopenia and lymphopenia. Neonatal throat swabs from three newborns were tested for 2019-nCoV, and all samples were negative for the nucleic acid of 2019-nCoV. One premature infant was transferred to Department of Neonatology due to low birth weight. By the end of February 25, 2020, none of the three patients developed severe 2019-nCoV pneumonia or died(two patients had been cured and discharged, while another one had been transferred to a square cabin hospital for isolation treatment). There were various degrees of fibrin deposition inside and around the villi with local syncytial nodule increases in all three placentas. One case of placenta showed the concomitant morphology of chorionic hemangioma and another one with massive placental infarction. No pathological change of villitis and chorioamnionitis was observed in our observation of three cases. All samples from three placentas were negative for the nucleic acid of 2019-nCoV. Conclusions: The clinical characteristics of pregnant women with 2019-nCoV infection in late pregnancy are similar to those of non-pregnant patients, and no severe adverse pregnancy outcome is found in the 3 cases of our observation. Pathological study suggests that there are no morphological changes related to infection in the three placentas. Currently no evidence for intrauterine vertical transmission of 2019-nCoV is found in the three women infected by 2019-nCoV in their late pregnancy.",2020,"Chen, S.; Huang, B.; Luo, D. J.; Li, X.; Yang, F.; Zhao, Y.; Nie, X.; Huang, B. X.",Zhonghua Bing Li Xue Za Zhi,3005679569,#3068,
,CZI,Detection of 2019-nCoV in the pathological paraffin embedded tissue,10.3760/cma.j.cn112151.20200219.00001,,32084674,,,2020,"Xu, S. P.; Kuang, D.; Hu, Y.; Liu, C.; Duan, Y. Q.; Wang, G. P.",Zhonghua Bing Li Xue Za Zhi,1757240742,#1448,
,CZI,Health management of breast cancer patients outside the hospital during the outbreak of 2019 novel coronavirus disease,10.3760/cma.j.cn112152-20200221-00110,,32100979,,"The outbreak of 2019 novel coronavirus disease (COVID-19) is spreading rapidly. In order to prevent cluster outbreaks, the government strengthened the management and control of personnel mobility, which had a great impact on the examination and treatment of breast cancer patients. This paper discusses how to realize scientific health management of breast cancer patients outside the hospital based on the existing epidemic situation, characteristics of breast cancer patients and public health safety factors. The breast cancer patients should synthetically consider the epidemic prevention situation of inhabitance, the disease stage and previous therapeutic schedule to decide the next therapeutic schedule. If necessary, after professional discussion and communication between doctors and patients online or offline, the hospital visiting time should be delayed through seeking alternative treatment schemes, and psychological counseling for patients should be paid attention to at the same time.",2020,"Liu, B. L.; Ma, F.; Wang, J. N.; Fan, Y.; Mo, H. N.; Xu, B. H.",Zhonghua Zhong Liu Za Zhi,2535587098,#2191,
,CZI,Surgical treatment strategy for digestive system malignancies during the outbreak of novel coronavirus pneumonia,10.3760/cma.j.cn112152-20200223-00117,,32096396,,"The outbreak of novel coronavirus pneumonia occurred in Wuhan, Hubei province of China, at the end of 2019, and spread rapidly across the country. After the outbreak of this disease, the overwhelming majority of cities have launched the ""first level response"" and the regular diagnosis and treatment of cancer patients are greatly affected. The digestive systemic cancer is the most common malignancy. Most patients are diagnosed in the advanced stage with poor prognosis. The epidemic of novel coronavirus pneumonia poses new challenges to diagnosis and treatment of the patients with digestive system malignancies. Based on the fully understanding of the characteristics of digestive system tumors, we should change the treatment strategy and adopt more reasonable treatment strategy timely during the epidemic period to minimize the adverse effects of the epidemic of novel coronavirus pneumonia on the treatment.",2020,"Ma, F. H.; Hu, H. T.; Tian, Y. T.",Zhonghua Zhong Liu Za Zhi,2366820445,#2176,
,CZI,[Surgical treatment for esophageal cancer during the outbreak of COVID-19],10.3760/cma.j.cn112152-20200226-00128,,32105052,,"Since December 2019, unexplained pneumonia has appeared in Wuhan City, Hubei Province, and a new type of coronavirus infection was confirmed as COVID-19. COVID-19 spread rapidly nationwide and abroad. The COVID-19 has brought huge impacts to all the people and walks of life, especially to the medical and health systems. It has also brought great challenges to the treatment of patients with cancer. Esophageal cancer is a common malignant tumor in China and most of the patients are in the middle and advanced stage when diagnosed, with immunosuppressive and poor prognosis. The selection of surgical procedures and perioperative managements of esophageal cancer require all thoracic surgeons work together to figure out a reasonable system of surgical treatment and emergency response.",2020,"Li, Y.; Qin, J. J.; Wang, Z.; Yu, Y.; Wen, Y. Y.; Chen, X. K.; Liu, W. X.",Zhonghua zhong liu za zhi [Chinese journal of oncology],1972328982,#2876,
,CZI,[Discussion on diagnosis and treatment of hepatobiliary malignancies during the outbreak of novel coronavirus pneumonia],10.3760/cma.j.cn112152-20200227-00137,,32108460,,"From December 2019, the new coronavirus pneumonia (COVID-19) broke out in Wuhan, Hubei, and spread rapidly to the nationwide. On January 20, 2020, the National Health Committee classified COVID-19 pneumonia as one of B class infectious diseases and treated it as class A infectious disease. During the epidemic period, the routine diagnosis and treatment of tumor patients was affected with varying degrees. In this special period, we performed the superiority of the multi-disciplinary team of diagnosis and treatment, achieved accurate diagnosis and treatment of patients with hepatobiliary malignant tumors, provided support for these patients with limited medical resources, and helped them to survive during the epidemic period.On the basis of fully understanding the new coronavirus pneumonia, the treatment strategy should be changed timely during the epidemic, and more appropriate treatment methods should be adopted to minimize the adverse effect of the epidemic on tumor treatment.",2020,"Wu, F.; Song, Y.; Zeng, H. Y.; Ye, F.; Rong, W. Q.; Wang, L. M.; Wu, J. X.",Zhonghua zhong liu za zhi [Chinese journal of oncology],3003637715,#2977,
,CZI,[Medical diagnosis and treatment strategies for malignant tumors of the digestive system during the outbreak of novel coronavirus pneumonia],10.3760/cma.j.cn112152-20200227-00141,,32112549,,"Since the outbreak of novel coronavirus pneumonia in December 2019, the diagnosis and treatment of patients with cancer have been facing great challenges. Although oncologists are not fighting on the front line to against the epidemic, during this special period, we should not only protect patients, their families and medical staff from the infection of novel Coronavirus, but also minimize the impact of the epidemic on the diagnosis and the treatment of patients with cancer. Combining the guidelines for diagnosis and treatment of tumors with our clinical experience, in this epidemic period, we discuss the strategies for diagnosis, treatment, and follow-up of malignant tumors of the digestive system in this article.",2020,"Zhang, Y.; Xu, J. M.",Zhonghua zhong liu za zhi [Chinese journal of oncology],1681405782,#3026,
,CZI,Individualized treatment recommendations for lung cancer patients at different stages of treatment during the outbreak of 2019 novel coronavirus disease epidemic,10.3760/cma.j.cn112152-20200228-00146,,32125130,,"In order to achieve the overall victory of the 2019 novel coronavirus disease epidemic in this 'war', especially to prevent the disease recurrence from rebounding during the resumption of labor, the government has not loosened any control of personnel mobility, which has obviously affected the normal examination and treatment of lung cancer patients under the influence of this epidemic. During the epidemic period, cancer patients with low immunity levels face the double ordeals of disease and epidemic situation. Compared with the general population, they are more likely to be infected with the new coronavirus. Among the infected cancer patients, lung cancer is the most common type. It is necessary to provide more appropriate individualized treatment recommendations for patients with lung cancer based on the epidemic situation of the patient's location and in combination with the patient's own condition. Through active prevention of infection, timely conversion of treatment strategies, online and offline joint control, and positive psychological counseling, we significantly hope to help patients with lung cancer to survive this difficult period.",2020,"Zhao, Z.; Bai, H.; Duan, J. C.; Wang, J.",Zhonghua Zhong Liu Za Zhi,58565763,#3237,
,CZI,Diagnostic and therapeutic strategies of lung cancer patients during the outbreak of 2019 novel coronavirus disease (COVID-19),10.3760/cma.j.cn112152-20200229-00152,,32118394,,"With the increasing number of cases and widening geographical spread, the 2019 novel coronavirus disease (COVID-19) has been classified as one of the class B infectious diseases but prevented and controlled as class A infectious disease by the National Health Commission of China. The diagnosis and treatment of lung cancer patients have been challenged greatly because of extraordinary public health measures since the lung cancer patients are a high-risk population during the COVID-19 outbreak period. Strict protection for lung cancer patients is needed to avoid infection. Lung cancer patients are difficult to differentiate from patients with COVID-19 in terms of clinical symptoms, which will bring great trouble to the clinical work and physical and mental health of lung cancer patients. This review will demonstrate how to applicate appropriate and individual management for lung cancer patients to protect them from COVID-19.",2020,"Yang, L.; Xu, H. Y.; Wang, Y.",Zhonghua Zhong Liu Za Zhi,2763173940,#3045,
,CZI,[The differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of the 2019 novel coronavirus disease],10.3760/cma.j.cn112152-20200303-00166,,32133833,,"Objective: To investigate the principles of differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of novel coronavirus (2019-nCoV) by analyzing one case of lymphoma who presented pulmonary ground-glass opacities (GGO) after courses of chemotherapy. Methods: Baseline demographics and clinicopathological data of eligible patients were retrieved from medical records. Information of clinical manifestations, history of epidemiology, lab tests and chest CT scan images of visiting patients from February 13 to February 28 were collected. Literatures about pulmonary infiltrates in cancer patients were searched from databases including PUBMED, EMBASE and CNKI. Results: Among the 139 cancer patients underwent chest CT scans before chemotherapy, pulmonary infiltrates were identified in eight patients (5.8%), five of whom were characterized as GGOs in lungs. 2019-nCoV nuclear acid testing was performed in three patients and the results were negative. One case was a 66-year-old man diagnosed as non-Hodgkin lymphoma and underwent CHOP chemotherapy regimen. His chest CT scan image displayed multiple GGOs in lungs and the complete blood count showed decreased lymphocytes. This patient denied any contact with confirmed/suspected cases of 2019-nCoV infection and without fever and other respiratory symptoms. Considering the negative result of nuclear acid testing, this patient was presumptively diagnosed as viral pneumonia and an experiential anti-infection treatment had been prescribed for him. Conclusions: The 2019 novel coronavirus disease (COVID-19) complicates the clinical scenario of pulmonary infiltrates in cancer patients. The epidemic history, clinical manifestation, CT scan image and lab test should be combined consideration. The 2019-nCoV nuclear acid testing might be applicated in more selected patients. Active anti-infection treatment and surveillance of patient condition should be initiated if infectious disease is considered.",2020,"Zhu, W. J.; Wang, J.; He, X. H.; Qin, Y.; Yang, S.; Hu, X. S.; Wang, H. Y.; Huang, J.; Zhou, A. P.; Ma, F.; Shi, Y. K.; Zhou, S. Y.",Zhonghua zhong liu za zhi [Chinese journal of oncology],2604139211,#5530,
,CZI,Study on assessing early epidemiological parameters of coronavirus disease epidemic in China,10.3760/cma.j.cn112338-20200205-00069,,32113196,,"Objective: To study the early dynamics of the epidemic of coronavirus disease (COVID-19) in China from 15 to 31 January, 2020, and estimate the corresponding epidemiological parameters (incubation period, generation interval and basic reproduction number) of the epidemic. Methods: By means of Weibull, Gamma and Lognormal distributions methods, we estimated the probability distribution of the incubation period and generation interval data obtained from the reported COVID-19 cases. Moreover, the AIC criterion was used to determine the optimal distribution. Considering the epidemic is ongoing, the exponential growth model was used to fit the incidence data of COVID-19 from 10 to 31 January, 2020, and exponential growth method, maximum likelihood method and SEIR model were used to estimate the basic reproduction number. Results: Early COVID-19 cases kept an increase in exponential growth manner before 26 January, 2020, then the increase trend became slower. The average incubation period was 5.01 (95%CI: 4.31-5.69) days; the average generation interval was 6.03 (95%CI: 5.20-6.91) days. The basic reproduction number was estimated to be 3.74 (95%CI: 3.63-3.87), 3.16 (95%CI: 2.90-3.43), and 3.91 (95%CI: 3.71-4.11) by three methods, respectively. Conclusions: The Gamma distribution fits both the generation interval and incubation period best, and the mean value of generation interval is 1.02 day longer than that of incubation period. The relatively high basic reproduction number indicates that the epidemic is still serious; Based on our analysis, the turning point of the epidemic would be seen on 26 January, the growth rate would be lower afterwards.",2020,"Song, Q. Q.; Zhao, H.; Fang, L. Q.; Liu, W.; Zheng, C.; Zhang, Y.",Zhonghua Liu Xing Bing Xue Za Zhi,3002764620,#3053,
,CZI,Dynamic basic reproduction number based evaluation for current prevention and control of COVID-19 outbreak in China,10.3760/cma.j.cn112338-20200209-00080,,32113197,,"Objective: To evaluate the current status of the prevention and control of coronavirus disease (COVID-19) outbreak in China, establish a predictive model to evaluate the effects of the current prevention and control strategies, and provide scientific information for decision- making departments. Methods: Based on the epidemic data of COVID-19 openly accessed from national health authorities, we estimated the dynamic basic reproduction number R(0)(t) to evaluate the effects of the current COVID-19 prevention and control strategies in all the provinces (municipalities and autonomous regions) as well as in Wuhan and the changes in infectivity of COVID-19 over time. Results: For the stability of the results, 24 provinces (municipality) with more than 100 confirmed COVID-19 cases were included in the analysis. At the beginning of the outbreak, the R(0)(t) showed unstable trend with big variances. As the strengthening of the prevention and control strategies, R(0)(t) began to show a downward trend in late January, and became stable in February. By the time of data analysis, 18 provinces (municipality) (75%) had the R(0)(t)s less than 1. The results could be used for the decision making to free population floating conditionally. Conclusions: Dynamic R(0)(t) is useful in the evaluation of the change in infectivity of COVID-19, the prevention and control strategies for the COVID-19 outbreak have shown preliminary effects, if continues, it is expected to control the COVID-19 outbreak in China in near future.",2020,"Huang, L. L.; Shen, S. P.; Yu, P.; Wei, Y. Y.",Zhonghua Liu Xing Bing Xue Za Zhi,1967501958,#3063,
,CZI,"Estimating the basic reproduction number of COVID-19 in Wuhan, China",10.3760/cma.j.cn112338-20200210-00086,,32125128,,"Objective: The number of confirmed and suspected cases of the COVID-19 in Hubei province is still increasing. However, the estimations of the basic reproduction number of COVID-19 varied greatly across studies. The objectives of this study are 1) to estimate the basic reproduction number (R(0)) of COVID-19 reflecting the infectiousness of the virus and 2) to assess the effectiveness of a range of controlling intervention. Method: The reported number of daily confirmed cases from January 17 to February 8, 2020 in Hubei province were collected and used for model fit. Four methods, the exponential growth (EG), maximum likelihood estimation (ML), sequential Bayesian method (SB) and time dependent reproduction numbers (TD), were applied to estimate the R(0). Result: Among the four methods, the EG method fitted the data best. The estimated R(0) was 3.49 (95% CI: 3.42-3.58) by using EG method. The R(0) was estimated to be 2.95 (95%CI: 2.86-3.03) after taking control measures. Conclusion: In the early stage of the epidemic, it is appropriate to estimate R(0) using the EG method. Meanwhile, timely and effective control measures were warranted to further reduce the spread of COVID-19.",2020,"Wang, Y.; You, X. Y.; Wang, Y. J.; Peng, L. P.; Du, Z. C.; Gilmour, S.; Yoneoka, D.; Gu, J.; Hao, C.; Hao, Y. T.; Li, J. H.",Zhonghua Liu Xing Bing Xue Za Zhi,3006535772,#3278,
,CZI,Prediction modeling with data fusion and prevention strategy analysis for the COVID-19 outbreak,10.3760/cma.j.cn112338-20200216-00107,,32129581,,"Since December 2019, the outbreak of COVID-19 in Wuhan has spread rapidly due to population movement during the Spring Festival holidays. Since January 23rd, 2020, the strategies of containment and contact tracing followed by quarantine and isolation has been implemented extensively in mainland China, and the rates of detection and confirmation have been continuously increased, which have effectively suppressed the rapid spread of the epidemic. In the early stage of the outbreak of COVID-19, it is of great practical significance to analyze the transmission risk of the epidemic and evaluate the effectiveness and timeliness of prevention and control strategies by using mathematical models and combining with a small amount of real-time updated multi-source data. On the basis of our previous research, we systematically introduce how to establish the transmission dynamic models in line with current Chinese prevention and control strategies step by step, according to the different epidemic stages and the improvement of the data. By summarized our modelling and assessing ideas, the model formulations vary from autonomous to non-autonomous dynamic systems, the risk assessment index changes from the basic regeneration number to the effective regeneration number, and the epidemic development and assessment evolve from the early SEIHR transmission model-based dynamics to the recent dynamics which are mainly associated with the variation of the isolated and suspected population sizes.",2020,"Tang, S. Y.; Xiao, Y. N.; Peng, Z. H.; Shen, H. B.",Zhonghua Liu Xing Bing Xue Za Zhi,1952209694,#4357,
,CZI,[Investigation and analysis on characteristics of a cluster of COVID-19 associated with exposure in a department store in Tianjin],10.3760/cma.j.cn112338-20200221-00139,,32133830,,"Objective: To describe the epidemiological characteristics of a cluster of COVID-19 cases reported in Baodi district of Tianjin as of 18 February, 2020, which might be associated with the exposure in a local department store, and provide suggestions for prevention and control strategy development. Methods: The basic characteristics, time and area distributions, clinical manifestations, epidemiological history and transmission mode of the COVID-19 cases associated with the department store exposure were analyzed. Results: A total of 40 COVID-19 cases were associated with the department store exposure, accounting for 75.47% of the total confirmed cases (53 cases) reported in Baodi district. The cases were mainly at the age of 60 years or older (35.00%) and farmers (40.00%). The main clinical manifestations included fever (95.00%), cough (35.00%), and diarrhea (15.00%). The proportion of confirmed severe cases was 32.50%. The incidence curve showed that the incidence peak occurred on 31 January, 2020. Among the 40 cases, 6(15.00%) were department store employees, 19(47.50%) were customers and 15(37.50%) were close contacts (secondary cases). The first case occurred on 21 January, 2020, this case was a department store employee who had a purchasing history at whole sale markets in other provinces and cities before the onset, and 3 employees were still on duty after symptom onsets. The median of the incubation period of customer cases was 6 days, and the median of the interval between onset and medical treatment of customer cases was 7 days. Conclusion: This was a cluster epidemic of COVID-19, which might be associated with the exposure in the department store. By now, the current prevention and control measures have achieved satisfied effects.",2020,"Wu, W. S.; Li, Y. G.; Wei, Z. F.; Zhou, P. H.; Lyu, L. K.; Zhang, G. P.; Zhao, Y.; He, H. Y.; Li, X. Y.; Gao, L.; Zhang, X. M.; Liu, H.; Zhou, N.; Guo, Y.; Zhang, D.; Liu, J.; Zhang, Y.",Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi,1608673380,#5319,
,CZI,[Potential false-positive rate among the 'asymptomatic infected individuals' in close contacts of COVID-19 patients],10.3760/cma.j.cn112338-20200221-00144,,32133832,,"Objective: As the prevention and control of COVID-19continues to advance, the active nucleic acid test screening in the close contacts of the patients has been carrying out in many parts of China. However, the false-positive rate of positive results in the screening has not been reported up to now. But to clearify the false-positive rate during screening is important in COVID-19 control and prevention. Methods: Point values and reasonable ranges of the indicators which impact the false-positive rate of positive results were estimated based on the information available to us at present. The false-positive rate of positive results in the active screening was deduced, and univariate and multivariate-probabilistic sensitivity analyses were performed to understand the robustness of the findings. Results: When the infection rate of the close contacts and the sensitivity and specificity of reported results were taken as the point estimates, the positive predictive value of the active screening was only 19.67%, in contrast, the false-positive rate of positive results was 80.33%. The multivariate-probabilistic sensitivity analysis results supported the base-case findings, with a 75% probability for the false-positive rate of positive results over 47%. Conclusions: In the close contacts of COVID-19 patients, nearly half or even more of the 'asymptomatic infected individuals' reported in the active nucleic acid test screening might be false positives.",2020,"Zhuang, G. H.; Shen, M. W.; Zeng, L. X.; Mi, B. B.; Chen, F. Y.; Liu, W. J.; Pei, L. L.; Qi, X.; Li, C.",Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi,2053265683,#5539,
,CZI,[Epidemiological analysis on a family cluster of COVID-19],10.3760/cma.j.cn112338-20200221-00147,,32133831,,"Objective: To understand the possible transmission route of a family cluster of COVID-19 in Zhengzhou and the potential infectivity of COVID-19 in incubation period, and provide scientific evidence for the timely control of infectious source and curb the spread of the epidemic. Methods: Epidemiological investigation was conducted for a family cluster of COVID-19 (8 cases) with descriptive epidemiological method, and respiratory tract samples of the cases were collected for the nucleic acid detection of 2019-nCoV by RT-PCR. Results: Two primary cases, which occurred on 31 January and 1 February, 2020, respectively, had a common exposure history in Wuhan. The other six family members had onsets on 30 January, 31 January, 1 February (three cases) and 3 February, 2020. Conclusions: In this family cluster of COVID-19, six family members were infected through common family exposure to the 2 primary cases. Five secondary cases had onsets earlier than or on the same day as the primary cases, indicating that COVID-19 is contagious in incubation period, and the home isolation in the early phase of the epidemic might lead to the risk of family cluster of COVID-19.",2020,"Qiu, Y. Y.; Wang, S. Q.; Wang, X. L.; Lu, W. X.; Qiao, D.; Li, J. B.; Gu, Y. Y.; Zeng, Y.; Chen, Y.; Bai, W. Z.; Xu, B. L.; Han, T. W.",Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi,2996261089,#4974,
,CZI,[Advances on presymptomatic or asymptomatic carrier transmission of COVID-19],10.3760/cma.j.cn112338-20200228-00207,,32141279,,"COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of ""the degree to which presymptomatic or asymptomatic infections can transmit"" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.",2020,"Gao, W. J.; Li, L. M.",Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi,2052037214,#4683,
,CZI,Mental health survey of 230 medical staff in a tertiary infectious disease hospital for COVID-19,10.3760/cma.j.cn121094-20200219-00063,,32131151,,"Objective: To investigate the mental health of clinical first-line medical staff in COVID-19 epidemic and provide theoretical basis for psychological intervention. Method: The mental health status of the first-line medical staff was investigated by Self-rating Anxiety Acale (SAS) and Post-Traumatic Stress Disorder Self-rating Scale(PTSD-SS). From February 7 to 14, 2020, 246 medical staff were investigated who participated in the treatment of COVID-19 using cluster sampling , and received 230 responses, with a recovery rate of 93.5%. Results: The incidence of anxiety in medical staff was 23.04% (53/230), and the score of SAS was (42.91 ± 10.89). Among them, the incidence of severe anxiety, moderate anxiety and mild anxiety were 2.17% (5/230), 4.78% (11/230) and 16.09% (37/230), respectively. The incidence of anxiety in female medical staff was higher than that in male [25.67% (48/187) vs 11.63% (5/43), Z=-2.008, P=0.045], the score of SAS in female medical staff was higher than that in male [(43.78±11.12) vs (39.14 ± 9.01), t =-2.548, P=0.012]. The incidence of anxiety in nurses was higher than that in doctors [26.88% (43/160) vs 14.29% (10/70), Z=-2.066, P=0.039], and the score of SAS in nurses was higher than that in doctors [(44.84±10.42) vs (38.50±10.72), t =-4.207, P<0.001]. The incidence of stress disorder in medical staff was 27.39% (63/230), and the score of PTSD-SS was (42.92 ± 17.88). The score of PTSD-SS in female medical staff was higher than that of male [(44.30±18.42) vs(36.91 ± 13.95), t=-2.472, P=0.014]. Conclusions: In COVID-19 epidemic, the incidence of anxiety and stress disorder is high among medical staff. Medical institutions should strengthen the training of psychological skills of medical staff. Special attention should be paid to the mental health of female nurses.",2020,"Huang, J. Z.; Han, M. F.; Luo, T. D.; Ren, A. K.; Zhou, X. P.",Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi,2393057990,#4557,
,CZI,Standardized diagnosis and treatment of colorectal cancer during the outbreak of novel coronavirus pneumonia in Renji hospital,10.3760/cma.j.cn441530-20200217-00057,,32084676,,"Novel coronavirus pneumonia (NCP) is currently raging in China. It has been proven that NCP can be transmitted from human to human and cause hospital infection, which seriously threatens surgical staffs and inpatients. Although colorectal surgery is not a front-line subject in the fight against the epidemic, but in this special situation, now it is a difficult task that with the premise of how to maximize the protection for patients and their families, health of medical staff, and the safety of wards and hospitals, we can provide the highest quality medical services to ensure the orderly development of previous clinical work. Referring to the ""Diagnosis and Treatment Scheme for NCP (Trial Version 4 and 5)"" and combining the actual practice situation in our hospital with the ""Summary of New Coronavirus Files of Shanghai Renji Hospital"", we summarize how to carry out the clinical practice of colorectal surgery under the situation of the prevention and control of the NCP epidemiology, meanwhile under such situation aiming the procedure of diagnose and treatment for emergency patients with colorectal tumor, we share the experiences of the diagnosis of colorectal tumor, the management of patients with colorectal cancer who are scheduled to be admitted for surgery, the protection of wards, the perioperative management. More importantly, we introduce in detail the operative management and perioperative management of colorectal surgery patients suspected or diagnosed with new coronary pneumonia, including prevention and control measures for medical staff, operating rooms and surgical instruments. The main points are as follows: (1) Multidisciplinary team (MDT) must be run through the diagnosis and treatment of colorectal cancer. The members include not only routine departments, but also respiratory department and infectious department. (2) Colonoscopy examination may cause cross infection of NCP to patients and doctors. Therefore, it is prior to examine the emergency cases and life-threatening patients (bleeding, obstruction, gastrointestinal foreign bodies, etc.). If the emergent patients (intestinal obstruction) with suspected or confirmed NCP, the surgeons must perform emergency surgery, and intestinal decompressive tube through colonoscopy is not recommended. (3) The colorectal cancer patients with suspected or confirmed NCP should be placed in the isolated room with separate medical devices, and the operative room with negative pressure (under-5 Pa) must be separated. All disposable medical items, body fluids and feces of the patients in perioperative periods must be unified disposed according to the medical waste standard. (4) The surgical medical workers who process colorectal cancer patients with NCP must be protected by three-level. After operation, the medical workers must receive medical observation and be isolated for 14 days. We hope our ""Renji experience"" will be beneficial to colleagues.",2020,"Luo, Y.; Zhong, M.",Zhonghua Wei Chang Wai Ke Za Zhi,2009124022,#1958,
,CZI,Thinking of treatment strategies for colorectal cancer patients in tumor hospitals under the background of coronavirus pneumonia,10.3760/cma.j.cn441530-20200217-00058,,32084675,,"In December 2019, a new outbreak of coronavirus pneumonia began to occur. Its pathogen is 2019-nCoV, which has the characteristics of strong infectivity and general susceptibility. The current situation of prevention and control of new coronavirus pneumonia is severe. In this context, as front-line medical workers bearing important responsibilities and pressure, while through strict management strategy, we can minimize the risk of infection exposure. By summarizing the research progress and guidelines in recent years in the fields of colorectal cancer disease screening, treatment strategies(including early colorectal cancer, locally advanced colorectal cancer, obstructive colorectal cancer, metastatic colorectal cancer and the treatment of patients after neoadjuvant therapy), the choice of medication and time limit for adjuvant therapy, the protective measures for patients undergoing emergency surgery, the re-examination of postoperative patients and the protection of medical staff, etc., authors improve treatment strategies in order to provide more choices for patients to obtain the best treatment under the severe epidemic situation of new coronavirus pneumonia. Meanwhile we hope that it can also provide more timely treatment modeling schemes for colleagues.",2020,"Hu, X. H.; Niu, W. B.; Zhang, J. F.; Li, B. K.; Yu, B.; Zhang, Z. Y.; Zhou, C. X.; Zhang, X. N.; Gao, Y.; Wang, G. Y.",Zhonghua Wei Chang Wai Ke Za Zhi,641660370,#1625,
,CZI,[Recommendations for the regulation of medical practices of burn treatment during the outbreak of the coronavirus disease 2019],10.3760/cma.j.cn501120-20200224-00083,,32111114,,"2019 novel coronavirus (2019-nCoV) is one of the beta coronaviruses and was identified as the pathogen of the severe ""coronavirus disease 2019 (COVID-19)"" in 2019. China has formally included the 2019-nCoV in the statutory notification and control system for infectious diseases according to the Law of the People's Republic of China on the Prevention and Treatment of Infectious Diseases. Currently, the national defending actions on the 2019-nCoV in China is in a critical period. Burn Department is also confronted with risk of infection by the 2019-nCoV. According to the guidelines on the diagnosis and treatment of COVID-19 (6(th) trial edition), the latest relative literature at home and abroad, the features of the COVID-19, recommendations for the COVID-19 prevention and control issued by the National Health Commission of China, and management experience of diagnosis and treatment in the related disciplines, we put forward recommendations for the medical practices of burn treatment during the outbreak of the COVID-19 in outpatient and emergency treatment, inpatient treatment, operation and ward management, etc. We hope these recommendations could benefit the professionals of the same occupation as us and related hospital managers, improve the treatment of burn during the outbreak of the COVID-19, and avoid or reduce the risk of infection of medical staff .",2020,"Ma, S. Y.; Yuan, Z. Q.; Peng, Y. Z.; Luo, Q. Z.; Song, H. P.; Xiang, F.; Tan, J. L.; Zhou, J. Y.; Li, N.; Hu, G. Z.; Luo, G. X.",Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns,2773264689,#2897,
,CZI,Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies,10.3760/cma.j.cn501120-20200224-00088,,32114747,,"Corona Virus Disease 2019 (COVID-19) has seriously affected the treatment of patients and social stability. In the later stage of disease, some COVID-19 patients may develop into acute respiratory distress syndrome or even multiple organ failure. However, one of the most important mechanism underlying the deterioration of disease is cytokine storm. At present, some therapies such as interleukin-6 antibody blocker, stem cell therapy, and transfusion of convalescent plasma have been applied to counteract the cytokine storm and have made some progress. This article reviews the influences of cytokine storm syndrome on the COVID-19 and the corresponding immunotherapies to resist cytokine storm.",2020,"Chen, C.; Zhang, X. R.; Ju, Z. Y.; He, W. F.",Zhonghua Shao Shang Za Zhi,2378303257,#3070,
,CZI,[COVID-19 complicated with DIC: 2 cases report and literatures review],10.3760/cma.j.issn.0253-2727.2020.0001,,32133824,,,2020,"Wang, Y. D.; Zhang, S. P.; Wei, Q. Z.; Zhao, M. M.; Mei, H.; Zhang, Z. L.; Hu, Y.",Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi,2980953248,#5291,
,CZI,"[Characteristics, causes, diagnosis and treatment of coagulation dysfunction in patients with COVID-19]",10.3760/cma.j.issn.0253-2727.2020.0002,,32133825,,,2020,"Mei, H.; Hu, Y.",Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi,2123029822,#4902,
,CZI,2019-nCoV: new challenges from coronavirus,10.3760/cma.j.issn.0253-9624.2020.0001,,32023682,,"The outbreak of pneumonia caused by the novel coronavirus 2019-nCoV in Wuhan, Hubei province of China, at the end of 2019 shaped tremendous challenges to China's public health and clinical treatment. The virus belongs to the β genus Coronavirus in the family Corornaviridae, and is closely related to SARS-CoV and MERS-CoV, causing severe symptoms of pneumonia. The virus is transmitted through droplets, close contact, and other means, and patients in the incubation period could potentially transmit the virus to other persons. According to current observations, 2019-nCoV is weaker than SARS in pathogenesis, but has stronger transmission competence; it's mechanism of cross-species spread might be related with angiotensin-converting enzyme Ⅱ (ACE2), which is consistent with the receptor SARS-CoV. After the outbreak of this disease, Chinese scientists invested a lot of energy to carry out research by developing rapid diagnostic reagents, identifying the characters of the pathogen, screening out clinical drugs that may inhibit the virus, and are rapidly developing vaccines. The emergence of 2019-nCoV reminds us once again of the importance of establishing a systematic coronavirus surveillance network. It also poses new challenges to prevention and control of the emerging epidemic and rapidly responses on scientific research.",2020,"Tian, H. Y.",Zhonghua Yu Fang Yi Xue Za Zhi,3006243359,#270,
,CZI,2019-nCoV: new challenges from coronavirus,10.3760/cma.j.issn.0253-9624.2020.0001,,,,"The outbreak of pneumonia caused by the novel coronavirus 2019-nCoV in Wuhan, Hubei province of China, at the end of 2019 shaped tremendous challenges to China's public health and clinical treatment. The virus belongs to the β genus Coronavirus in the family Corornaviridae, and is closely related to SARS-CoV and MERS-CoV, causing severe symptoms of pneumonia. The virus is transmitted through droplets, close contact, and other means, and patients in the incubation period could potentially transmit the virus to other persons. According to current observations, 2019-nCoV is weaker than SARS in pathogenesis, but has stronger transmission competence; it's mechanism of cross-species spread might be related with angiotensin-converting enzyme Ⅱ (ACE2), which is consistent with the receptor SARS-CoV. After the outbreak of this disease, Chinese scientists invested a lot of energy to carry out research by developing rapid diagnostic reagents, identifying the characters of the pathogen, screening out clinical drugs that may inhibit the virus, and are rapidly developing vaccines. The emergence of 2019-nCoV reminds us once again of the importance of establishing a systematic coronavirus surveillance network. It also poses new challenges to prevention and control of the emerging epidemic and rapidly responses on scientific research.",2020,"TIAN, Huai Yu",Chinese Journal of Preventive Medicine,3006243359,#270,
,CZI,Be alert to superposed effect of seasonal influenza while fighting against novel coronavirus pneumonia,10.3760/cma.j.issn.0253-9624.2020.0002,,32040985,,"The novel coronavirus pneumonia (NCP) continues to spread throughout the country, and the prevention and control of the epidemic has entered a critical period. However, southern cities with severe outbreaks are about to enter the seasonal influenza season. We should strengthen the epidemiological investigation, optimize the laboratory testing strategy, take effective measures, strengthen the prevention and control of influenza epidemic, and minimize the interference to the new coronavirus epidemic.",2020,"Li, T. G.; Wang, M.",Zhonghua Yu Fang Yi Xue Za Zhi,2015989058,#696,
,CZI,"The network investigation on knowledge, attitude and practice about Novel coronavirus pneumonia of the residents in Anhui Province",10.3760/cma.j.issn.0253-9624.2020.0004,,32064854,,"Objective: To analyze the current situation of the knowledge, attitudes and practice about Novelcoronavirus pneumonia (NCP) of the residents in Anhui Province. Methods: Anonymous network sampling survey was carried out with an electronic questionnaire that designed by the questionnaire star, and a total of 4016 subjects from Anhui province were investigated. The content of the survey includes that the basic information of subjects,the residents' knowledge, attitudes and practice about NCP, as well as their satisfaction with the prevention and control measures adopted by the government and health authorities and the suggestions on future prevention. The questionnaire doesn't involve any privacy information, and all questions were mandatory to ensure the response rate. Results: The M (P(25), P(75)) age the 4016 subjects was 21 (19, 24), and the ranging from 7 to 80 years old. The number of males was1431(35.6%). Social networking tools such as WeChat and QQ were the main sources of epidemic information for residents (97.8%, 3 929 respondents). Residents have a high awareness rate of the main symptoms, transmission routes, using of masks, hand washing and treatment information of NCP, while a low awareness rate of the atypical symptoms. 92.6% of the subjects (n=3 720) think that the outbreak was scary. In terms of psychological behavior scores, the results showed that female (9.38±4.81), the urban (9.37±5.02) and the medical workers (10.79±5.19) had a poorer mental health than the male (8.45±5.00) , the rural (8.71±4.75) and the non-medical workers (the students: 8.85±4.83; public institude workers: 9.02±5.08; others: 8.97±5.39) (P < 0.05). 71.9% of the residents (n=2 887)were satisfied with the local epidemic control measures. The residents took various of the measures to prevent and control the epidemic. The ratio of residents that could achieve ""no gathering and less going out"" , ""wear masks when going out"" and ""do not go to crowded and closed places"" was up to 97.4% (n=3 913), 93.6% (n=3758) and 91.5% (n=3 673) respectively. Conclusion: The residents in Anhui province have a good KAP about NCP, yet it is necessary to strengthen the community publicity, the mental health maintenance of residents and students' health education.",2020,"Chen, Y.; Jin, Y. L.; Zhu, L. J.; Fang, Z. M.; Wu, N.; Du, M. X.; Jiang, M. M.; Wang, J.; Yao, Y. S.",Zhonghua Yu Fang Yi Xue Za Zhi,2363410972,#2333,
,CZI,Analysis of the first cluster of cases in a family of novel coronavirus pneumonia in Gansu Province,10.3760/cma.j.issn.0253-9624.2020.0005,,32064855,,"The epidemiological history and clinical characteristics of 7 cases of COVID-19 and 1 case of close contact in the first family aggregation epidemic of COVID-19 in Gansu Province were analyzed. The first patient A developed on January 22, 2020, with a history of residence in Wuhan, and confirmed severe cases of NCP on January 24, 2020; patient B, on January 23, 2020, diagnosed on January 31, severe cases; patient C, asymptomatic, diagnosed on January 27; patient D, asymptomatic, diagnosed on January 27; patient E, on January 24, diagnosed on January 28; patient F, asymptomatic, diagnosed on January 31; Patient G was asymptomatic and was diagnosed on January 31. In close contact, H was asymptomatic, PCR test was negative and asymptomatic, and he was discharged early. Among the 7 patients, 1 case died of (B) aggravation, and the other patients' condition was effectively controlled after active treatment. Except for the discharged cases, 5 cases were positive for COVID-19 specific IgM antibody and 1 case was negative. In this clustering outbreak, 4 patients remained asymptomatic, but PCR and IgM antibodies were positive, indicating that asymptomatic patients may be the key point to control the epidemic. Specific IgM antibody screening for patients whose pharyngeal swab nucleic acid test is negative but with ground glass-like lung lesions is very important for early detection and early isolation.",2020,"Bai, S. L.; Wang, J. Y.; Zhou, Y. Q.; Yu, D. S.; Gao, X. M.; Li, L. L.; Yang, F.",Zhonghua Yu Fang Yi Xue Za Zhi,3005670878,#2370,
,CZI,Analysis of the first cluster of cases in a family of novel coronavirus pneumonia in Gansu Province,10.3760/cma.j.issn.0253-9624.2020.0005,,32064855,,"The epidemiological history and clinical characteristics of 7 cases of COVID-19 and 1 case of close contact in the first family aggregation epidemic of COVID-19 in Gansu Province were analyzed. The first patient A developed on January 22, 2020, with a history of residence in Wuhan, and confirmed severe cases of NCP on January 24, 2020; patient B, on January 23, 2020, diagnosed on January 31, severe cases; patient C, asymptomatic, diagnosed on January 27; patient D, asymptomatic, diagnosed on January 27; patient E, on January 24, diagnosed on January 28; patient F, asymptomatic, diagnosed on January 31; Patient G was asymptomatic and was diagnosed on January 31. In close contact, H was asymptomatic, PCR test was negative and asymptomatic, and he was discharged early. Among the 7 patients, 1 case died of (B) aggravation, and the other patients' condition was effectively controlled after active treatment. Except for the discharged cases, 5 cases were positive for COVID-19 specific IgM antibody and 1 case was negative. In this clustering outbreak, 4 patients remained asymptomatic, but PCR and IgM antibodies were positive, indicating that asymptomatic patients may be the key point to control the epidemic. Specific IgM antibody screening for patients whose pharyngeal swab nucleic acid test is negative but with ground glass-like lung lesions is very important for early detection and early isolation.;",2020,"Bai, Shaoli; Wang, Jianyun; Zhou, Yingquan; Yu, Desheng; Gao, Xiaomin; Li, Lingling; Yang, Fan",Chinese Journal of Preventive Medicine,3005670878,#2370,
,CZI,Early containment strategies and core measures for prevention and control of novel coronavirus pneumonia in China,10.3760/cma.j.issn.0253-9624.2020.03.003,,32064856,,"In December 2019, novel coronavirus pneumonia epidemic occurred in Wuhan, Hubei Province, and spread rapidly across the country. In the early stages of the epidemic, China adopted the containment strategy and implemented a series of core measures around this strategic point, including social mobilization, strengthening case isolation and close contacts tracking management, blocking epidemic areas and traffic control to reduce personnel movements and increase social distance, environmental measures and personal protection, with a view to controlling the epidemic as soon as possible in limited areas such as Wuhan. This article summarizes the background, key points and core measures in the country and provinces. It sent prospects for future prevention and control strategies.",2020,"Chen, W.; Wang, Q.; Li, Y. Q.; Yu, H. L.; Xia, Y. Y.; Zhang, M. L.; Qin, Y.; Zhang, T.; Peng, Z. B.; Zhang, R. C.; Yang, X. K.; Yin, W. W.; An, Z. J.; Wu, D.; Yin, Z. D.; Li, S.; Chen, Q. L.; Feng, L. Z.; Li, Z. J.; Feng, Z. J.",Zhonghua Yu Fang Yi Xue Za Zhi,2995124404,#1159,
,CZI,Urgent research agenda for the novel coronavirus epidemic: transmission and non-pharmaceutical mitigation strategies,10.3760/cma.j.issn.0254-6450.2020.02.001,,32026672,,,2020,"Strategy; Policy Working Group for, Ncip Epidemic Response",Zhonghua Liu Xing Bing Xue Za Zhi,3002539152,#428,
,CZI,An update on the epidemiological characteristics of novel coronavirus pneumonia(COVID-19),10.3760/cma.j.issn.0254-6450.2020.02.002,,32057211,,"Through literature review and group discussion, Special Expert Group for Control of the Epidemic of Novel Coronavirus Pneumonia of the Chinese Preventive Medicine Association formulated an update on the epidemiological characteristics of novel coronavirus pneumonia (NCP). The initial source of the 2019 novel coronavirus (2019-nCoV) was the Huanan seafood market in Wuhan, Hubei province, China, with pangolins as a potential animal host. Currently the main source of infection is NCP patients, and asymptomatic carriers may also be infectious. The virus is believed transmitted mostly via droplets or contact. People are all generally susceptible to the virus. The average incubation period was 5.2 days, and the basic reproductive number R(0) was 2.2 at the onset of the outbreak. Most NCP patients were clinically mild cases. The case fatality rate was 2.38%, and elderly men with underlying diseases were at a higher risk of death. Strategies for prevention and control of NCP include improving epidemic surveillance, quarantining the source of infection, speeding up the diagnosis of suspected cases, optimizing the management of close contacts, tightening prevention and control of cluster outbreaks and hospital infection, preventing possible rebound of the epidemic after people return to work from the Chinese Spring Festival holiday, and strengthening community prevention and control.",2020,"Special Expert Group for Control of the Epidemic of Novel Coronavirus Pneumonia of the Chinese Preventive Medicine, Association",Zhonghua Liu Xing Bing Xue Za Zhi,,#915,
,CZI,The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China,10.3760/cma.j.issn.0254-6450.2020.02.003,,32064853,,"Objective: An outbreak of 2019 novel coronavirus diseases (COVID-19) in Wuhan, China has spread quickly nationwide. Here, we report results of a descriptive, exploratory analysis of all cases diagnosed as of February 11, 2020. Methods: All COVID-19 cases reported through February 11, 2020 were extracted from China's Infectious Disease Information System. Analyses included: 1) summary of patient characteristics; 2) examination of age distributions and sex ratios; 3) calculation of case fatality and mortality rates; 4) geo-temporal analysis of viral spread; 5) epidemiological curve construction; and 6) subgroup analysis. Results: A total of 72 314 patient records-44 672 (61.8%) confirmed cases, 16 186 (22.4%) suspected cases, 10567 (14.6%) clinical diagnosed cases (Hubei only), and 889 asymptomatic cases (1.2%)-contributed data for the analysis. Among confirmed cases, most were aged 30-79 years (86.6%), diagnosed in Hubei (74.7%), and considered mild (80.9%). A total of 1 023 deaths occurred among confirmed cases for an overall case-fatality rate of 2.3%. The COVID-19 spread outward from Hubei sometime after December 2019 and by February 11, 2020, 1 386 counties across all 31 provinces were affected. The epidemic curve of onset of symptoms peaked in January 23-26, then began to decline leading up to February 11. A total of 1 716 health workers have become infected and 5 have died (0.3%). Conclusions: The COVID-19 epidemic has spread very quickly. It only took 30 days to expand from Hubei to the rest of Mainland China. With many people returning from a long holiday, China needs to prepare for the possible rebound of the epidemic.",2020,"Novel Coronavirus Pneumonia Emergency Response Epidemiology, Team",Zhonghua Liu Xing Bing Xue Za Zhi,3005943294,#1123,
,CZI,"Cluster investigation Technical Guidelines for the 2019 Novel Coronavirus Pneumonia (COVID-19), China (1st Trial Version)",10.3760/cma.j.issn.0254-6450.2020.03.001,,32061201,,,2020,"Epidemiology Working Group, Strategy; Policy Working Group for Ncip Epidemic Response, Chinese Center for Disease Control; Prevention",Zhonghua Liu Xing Bing Xue Za Zhi,3002539152,#1012,
,CZI,Consideration on the strategies during epidemic stage changing from emergency response to continuous prevention and control,10.3760/cma.j.issn.0254-6450.2020.03.003,,32088947,,,2020,"Special Expert Group for Control of the Epidemic of Novel Coronavirus Pneumonia of the Chinese Preventive Medicine, Association",Zhonghua Liu Xing Bing Xue Za Zhi,2335493203,#1765,
,CZI,"Interpretation of ""Guidelines for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Infection by the National Health Commission (Trial Version 5)""",10.3760/cma.j.issn.0376-2491.2020.0001,,32033513,,"the National Health Commission of the People's Republic of China publish the guidelines for the diagnosis and treatment of novel coronavirus (2019-nCoV) infection (trial version 5) .With the awareness and understanding of the disease, the guidelines have been revised for recognize, treat, and prevent diseases. Then, what are the contents of the fifth edition of the guide issued updated compared to the fourth edition, now, learn together.",2020,"Lin, L.; Li, T. S.",Zhonghua Yi Xue Za Zhi,3004824173,#479,
,CZI,"The way to reduce the""false negative results""of 2019 novel coronavirus nucleic acid detection",10.3760/cma.j.issn.0376-2491.2020.0008,,32072795,,,2020,"Zhang, R.; Li, J. M.",Zhonghua Yi Xue Za Zhi,3005656138,#1257,
,CZI,Suggestions for disinfection of ophthalmic examination equipment and protection of ophthalmologist against 2019 novel coronavirus infection,10.3760/cma.j.issn.0412-4081.2020.0001,,32035428,,"At present, the prevention and treatment of 2019 Novel Coronavirus (2019-nCoV) in China has reached a critical stage. It is extremely important to disinfect ophthalmic examination instruments and protect ophthalmic medical care during the epidemic period to reduce cross-infection in clinical practice and reduce the infection risk of ophthalmic medical staff. (Chin J Ophthalmol, 2020, 56: 0001).",2020,"Zhang, M. C.; Xie, H. T.; Xu, K. K.; Cao, Y.",Zhonghua Yan Ke Za Zhi,2982939398,#555,
,CZI,Suggestions from ophthalmic experts on eye protection during the novel coronavirus pneumonia epidemic,10.3760/cma.j.issn.0412-4081.2020.0002,,32061202,,,2020,"Society of Public Health Ophthalmology, Chinese Preventive Medicine Association; Beijing Ophthalmological, Society; Youth Committee of Beijing Ophthalmological, Society",Zhonghua Yan Ke Za Zhi,2166867592,#1006,
,CZI,Recommendations for general surgery clinical practice in novel coronavirus pneumonia situation,10.3760/cma.j.issn.0529-5815.2020.0001,,32057212,,"Novel coronavirus pneumonia (NCP) is a highly infectious disease, has a long incubation period and a variety of clinical manifestations, which has a significant impact on public health and life. Afterwards, scientific and standardized work processing during the epidemic is of great significance for prevention and control. In order to implement the central government's decision-making deployment and defeat the NCP as soon as possible, we had focused on the key points in the clinical work of general surgery according to latest relevant guidelines, literature and experience in epidemic prevention. Finally, we drafted the prevention and control strategies and recommendations to make a reference for medical staff of general surgery to fight NCP.",2020,"TAO, Kai xiong; ZHANG, Bi xiang; ZHANG, Peng; ZHU, Peng; WANG, Guo bin; CHEN, Xiao ping",Chinese Journal of Surgery,3006604045,#1027,
,CZI,Countermeasures and treatment for aortic acute syndrome with novel coronavirus pneumonia,10.3760/cma.j.issn.0529-5815.2020.0002,,32066206,,"The novel coronavirus pneumonia (NCP) has cost a great loss to the health and economic property of Chines people. Under such a special circumstance, how to deal with such patients with acute aortic syndrome has become a serious challenge. Rapid diagnosis of concomitant NCP, safe and effective transportation, implementation of the interventional procedure, protection of vascular surgical team and postoperative management and follow-up of such patients have become urgent problems for us. Combined with the latest novel government documents, the literature and the experiences from Wuhan, we answered the above questions briefly and plainly. It also hopes to inspire the national vascular surgeons to manage critical emergencies in vascular surgery and even routine vascular diseases with NCP, as a final point to limit the severe epidemic situation, and minimize the damage of NCP.",2020,"Si, Y.; Sun, X. F.; Zhong, M.; Yue, J. N.; Fu, W. G.",Zhonghua Wai Ke Za Zhi,2132260239,#1176,
,CZI,Facing the pandemic of 2019 novel coronavirus infections: the pediatric perspectives,10.3760/cma.j.issn.0578-1310.2020.0001,,32023678,,,2020,"Fang, F.; Luo, X. P.",Zhonghua Er Ke Za Zhi,3005240180,#325,
,CZI,First case of 2019 novel coronavirus infection in children in Shanghai,10.3760/cma.j.issn.0578-1310.2020.0002,,32023679,,,2020,"Cai, J. H.; Wang, X. S.; Ge, Y. L.; Xia, A. M.; Chang, H. L.; Tian, H.; Zhu, Y. X.; Wang, Q. R.; Zeng, J. S.",Zhonghua Er Ke Za Zhi,3004790666,#340,
,CZI,Prevention and control program on 2019 novel coronavirus infection in Children's digestive endoscopy center,10.3760/cma.j.issn.0578-1310.2020.0003,,32023683,,,2020,"Subspecialty Group of Gastroenterology, the Society of Pediatrics Chinese Medical Association",Zhonghua Er Ke Za Zhi,3004896587,#272,
,CZI,"Recommendations for the diagnosis, prevention and control of the 2019 novel coronavirus infection in children (first interim edition)",10.3760/cma.j.issn.0578-1310.2020.0004,,32035429,,,2020,"Society of Pediatrics, Chinese Medical Association; Editorial Board, Chinese Journal of Pediatrics",Zhonghua Er Ke Za Zhi,3004790666,#558,
,CZI,Frist case of severe childhood novel coronavirus pneumonia in China,10.3760/cma.j.issn.0578-1310.2020.0005,,32045966,,"1例主诉为""间断腹泻、呕吐6 d,发热伴呼吸急促半天""的患儿就诊于武汉儿童医院重症医学科,诊断为儿童危重型新型冠状病毒肺炎(NCP)。以""新型冠状病毒肺炎""""儿童""""危重型"" 为关键词检索截至2020年2月8日中国知网、维普网、万方等相关数据库,未见报道。本例为中国首例危重型NCP患儿,以消化道症状起病,早期呼吸道症状 不明显,快速进展为急性呼吸窘迫综合征、脓毒症休克并伴有急性肾衰竭。患儿早期连续2次咽拭子2019新型冠状病毒(2019-nCoV)核酸检测阴性。 对于重症疑似病例,建议采集下呼吸道样本或重复采集上呼吸道样本进行检测。体外连续血液净化技术可尽早应用到危重型NCP患儿的救治中。",2020,"Chen, F.; Liu, Z. S.; Zhang, F. R.; Xiong, R. H.; Chen, Y.; Cheng, X. F.; Wang, W. Y.; Ren, J.",Zhonghua Er Ke Za Zhi,3004790666,#790,
,CZI,First case of severe childhood novel coronavirus pneumonia in China,10.3760/cma.j.issn.0578-1310.2020.0005,,32045967,,,2020,"CHEN, Feng; LIU, Zhi sheng; ZHANG, Fu rong; XIONG, Rui hua; CHEN, Yang; CHENG, X Feng; WANG, Wen yong; REN, Jie",Chinese Journal of Pediatrics,3004790666,#3588,
,CZI,2019-novel coronavirus infection in a three-month-old baby,10.3760/cma.j.issn.0578-1310.2020.0006,,32043842,,,2020,"Zhang, Y. H.; Lin, D. J.; Xiao, M. F.; Wang, J. C.; Wei, Y.; Lei, Z. X.; Zeng, Z. Q.; Li, L.; Li, H. A.; Xiang, W.",Zhonghua Er Ke Za Zhi,2951323607,#699,
,CZI,Analysis of CT features of 15 Children with 2019 novel coronavirus infection,10.3760/cma.j.issn.0578-1310.2020.0007,,32061200,,"Objective: To explore imaging characteristics of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: A retrospective analysis was performed on clinical data and chest CT images of 15 children diagnosed with 2019-nCoV. They were admitted to the third people's Hospital of Shenzhen from January 16 to February 6, 2020. The distribution and morphology of pulmonary lesions on chest CT images were analyzed. Results: Among the 15 children, there were 5 males and 10 females, aged from 4 to 14 years old. Five of the 15 children were febrile and 10 were asymptomatic on first visit. The first nasal or pharyngeal swab samples in all the 15 cases were positive for 2019-nCoV nucleic acid. For their first chest CT images, 6 patients had no lesions, while 9 patients had pulmonary inflammation lesions. Seven cases of small nodular ground glass opacities and 2 cases of speckled ground glass opacities were found. After 3 to 5 days of treatment, 2019-nCoV nucleic acid in a second respiratory sample turned negative in 6 cases. Among them, chest CT images showed less lesions in 2 cases, no lesion in 3 cases, and no improvement in 1 case. Other 9 cases were still positive in a second nucleic acid test. Six patients showed similar chest CT inflammation, while 3 patients had new lesions, which were all small nodular ground glass opacities. Conclusions: The early chest CT images of children with 2019-nCoV infection are mostly small nodular ground glass opacities. The clinical symptoms of children with 2019-nCoV infection are nonspecific. Dynamic reexamination of chest CT and nucleic acid are important.",2020,"Feng, K.; Yun, Y. X.; Wang, X. F.; Yang, G. D.; Zheng, Y. J.; Lin, C. M.; Wang, L. F.",Zhonghua Er Ke Za Zhi,3004906315,#1011,
,CZI,Clinical and epidemiological characteristics of 34 children with 2019 novel coronavirus infection in Shenzhen,10.3760/cma.j.issn.0578-1310.2020.0008,,32062875,,"Objective: To describe the characteristics of clinical manifestations and epidemiology of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: All 34 children with laboratory-confirmed 2019-nCoV infection by quantitative real-time reverse transcription-PCR through nasopharyngeal swab specimens were admitted to the Third People's Hospital of Shenzhen from January 19 to Febuary 7, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. Results: Among the 34 cases, 14 were males, and 20 were females. The median age was 8 years and 11 months. No patients had underlying diseases. There were 28 children (82%) related with a family cluster outbreak. There were 26 children (76%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 22 (65%) common cases, 9 (26%) mild cases and 3 (8.8%) asymptomatic cases. No severe or critical cases were identified. The most common symptoms were fever (17 cases, 50%) and cough (13 cases, 38% ). In the 34 cases, the white blood cell counts of 28 cases (82%) were normal. Five cases had white blood cell counts more than 10×10(9)/L. One case had white blood cell counts less than 4×10(9)/L. Neutropenia and lymphopenia was found in one case, respectively. C-reactive protein levels and erythrocyte sedimentation rates were elevated in 1 and 5 case, respectively. Elevated procalcitonin was found in 1 case and D-Dimer in 3 cases. The levels of lactic dehydrogenase (LDH) were more than 400 U/L in 10 cases. The CT images of these patients showed bilateral multiple patchy or nodular ground-glass opacities and/or infiltrating shadows in middle and outer zone of the lung or under the pleura. Twenty patients were treated with lopinavir and ritonavir. Glucocorticoids and immunoglobulin were not used in any cases. All the cases improved and were discharged from hospital. Further following up was need. Conclusions: The clinical manifestations in children with 2019-nCoV infection are non-specific and are milder than that in adults. Chest CT scanning is heplful for early diagnosis. Children's infection is mainly caused by family cluster outbreak and imported cases. Family daily prevention is the main way to prevent 2019-nCoV infection.",2020,"Wang, X. F.; Yuan, J.; Zheng, Y. J.; Chen, J.; Bao, Y. M.; Wang, Y. R.; Wang, L. F.; Li, H.; Zeng, J. X.; Zhang, Y. H.; Liu, Y. X.; Liu, L.",Zhonghua Er Ke Za Zhi,3002108456,#1004,
,CZI,First case of neonate infected with novel coronavirus pneumonia in China,10.3760/cma.j.issn.0578-1310.2020.0009,,32065520,,,2020,"Zeng, L. K.; Tao, X. W.; Yuan, W. H.; Wang, J.; Liu, X.; Liu, Z. S.",Zhonghua Er Ke Za Zhi,3004790666,#1084,
,CZI,Noninvasive Respiratory Support for Novel Coronavirus Pneumonia: Enough is Enough,10.3760/cma.j.issn.0578-1426.2020.0006,,32129582,,,2020,"Pan, C.; Zhang, W.; Xia, J. A.; Liu, H.; Du, B.; Qiu, H. B.",Zhonghua Nei Ke Za Zhi,3005255913,#4355,
,CZI,Diagnosis and clinical management of 2019 novel coronavirus infection: an operational recommendation of Peking Union Medical College Hospital (V2.0),10.3760/cma.j.issn.0578-1426.2020.03.003,,32023681,,"Since December 2019, China has been experiencing an outbreak of new infectious disease caused by 2019 novel coronavirus (2019-nCoV). The clinical features include fever, coughing, shortness of breath, and inflammatory pulmonary infiltration revealed by X ray. China rapidly identified 2019-nCoV-related pneumonia a statutory infectious disease. To standardize the diagnosis and treatment of this new infectious disease, operational guidelines for the diagnosis and management of 2019-nCoV infection is accomplished by Peking Union Medical College Hospital.",2020,"Working Group of Novel Coronavirus, Peking Union Medical College Hospital",Zhonghua Nei Ke Za Zhi,3005477624,#259,
,CZI,Efficient management of novel coronavirus pneumonia by efficient prevention and control in scientific manner,10.3760/cma.j.issn.1001-0939.2020.0001,,32023684,,"At the end of 2019, sporadic and clustered case with ""pneumonia of unknown origin"" emerged in Wuhan, Hubei province. The causative pathogen was quickly confirmed as ""2019-nCoV"" . The epidemic soon spread throughout the country and became a pandemic in over a month. Government and medical institutions across the country mobilized all kinds of resources and took a variety of measures to actively treat patients and stop the epidemic. Based on current studies, the author summarized the clinical characteristics and evolution of the novel viral pneumonia, and proposed the key points of diagnosis and treatment, the scientific management of both confirmed and suspected cases, and the scientific management of disease prevention and control.",2020,"Gao, Z. C.",Zhonghua Jie He He Hu Xi Za Zhi,2115137097,#324,
,CZI,Potential antiviral therapeutics for 2019 Novel Coronavirus,10.3760/cma.j.issn.1001-0939.2020.0002,,32023685,,"The recent outbreak of respiratory illness in Wuhan, China is caused by a novel coronavirus, named 2019-nCoV, which is genetically close to a bat-derived coronavirus. 2019-nCoV is categorized as beta genus coronavirus, same as the two other strains - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir / ritonavir, lopinavir / ritonavir combined with interferon-β, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for 2019-nCoV pneumonia patients need to be assessed by further clinical trials.",2020,"Li, H.; Wang, Y. M.; Xu, J. Y.; Cao, B.",Zhonghua Jie He He Hu Xi Za Zhi,3004878749,#309,
,CZI,Early detection and disease assessment of patients with novel coronavirus pneumonia,10.3760/cma.j.issn.1001-0939.2020.0003,,32023686,,"In December 2019, the outbreak of novel coronavirus (2019- nCoV) in wuhan, China, attracting attention worldwidely. The novel coronavirus has the characteristics of rapid transmission, atypical clinical symptoms, and easy to affect both lungs, leading to missed diagnosis and misdiagnosis, as well as difficult to detection and assessment at early stage. Fever, cough, myalgia, weakness, dyspnea and imagings may be helpful for the early detection of novel coronavirus pneumonia. At the same time, the rate of disease progression, fever, CT manifestations, hypoxia degree, age, basic diseases, and laboratory indicators can also be used to evaluate the severity of the novel coronavirus pneumonia.",2020,"Zhou, L.; Liu, H. G.",Zhonghua Jie He He Hu Xi Za Zhi,2481602709,#247,
,CZI,Pulmonary rehabilitation guidelines in the principle of 4S for patients infected with 2019 novel coronavirus (2019-nCoV),10.3760/cma.j.issn.1001-0939.2020.0004,,32023687,,"A recent epidemic of pneumonia cases in Wuhan China was caused by a novel coronavirus with strong infectivity, the 2019 novel coronavirus (2019-nCoV). The article provides the pulmonary rehabilitation (PR) methods in the principle of 4S (simple, safe, satisfy, save) for patients with pneumonia caused by the novel coronavirus, shows how to establish a ventilative and convectional PR environment to prevent the spread of virus through droplets, how to guide the patients to carry out PR, how to carry out respiratory muscle training, effective cough, expectoration, sneeze, general exercise, digestive function rehabilitation and psychological rehabilitation, and how to clean and disinfect the PR environment.",2020,"Yang, F.; Liu, N.; Wu, J. Y.; Hu, L. L.; Su, G. S.; Zheng, N. S.",Zhonghua Jie He He Hu Xi Za Zhi,3005028983,#252,
,CZI,Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia,10.3760/cma.j.issn.1001-0939.2020.0005,,32026671,,"Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients,serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased(15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mildgroup. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-α), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.",2020,"Chen, L.; Liu, H. G.; Liu, W.; Liu, J.; Liu, K.; Shang, J.; Deng, Y.; Wei, S.",Zhonghua Jie He He Hu Xi Za Zhi,3001118548,#473,
,CZI,Expert consensus for bronchoscopy during the epidemic of 2019 Novel Coronavirus infection (Trial version),10.3760/cma.j.issn.1001-0939.2020.0006,,32033514,,"Infection with 2019 Novel Coronavirus (2019-nCoV) is mainly transmitted by respiratory droplets, airborne transmission and direct contact. However, conducting bronchoscopy on patients with 2019-nCoV is a high-risk procedure in which health care workers are directly exposed to the virus, and the protection and operation procedures need to be strictly regulated. According to the characteristics of bronchoscopy, it is necessary to formulate the procedure, requirements and precautions when conducting bronchoscopy in the current epidemic situation. Relevant standards for preventing from infections should be strictly implemented in the operation of bronchoscopy. It needs to emphasize that bronchoscopy should not be used as a routine means for the diagnosis of 2019-nCoV infection sampling. The indications for bronchoscopy for other diseases should be strictly mastered, and it is suggested that bronchoscopy should be postponed for those patients who is not in urgent situation.",2020,"Group of Interventional Respiratory Medicine, Chinese Thoracic Society",Zhonghua Jie He He Hu Xi Za Zhi,3004450134,#481,
,CZI,Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia,10.3760/cma.j.issn.1001-0939.2020.0007,,32034899,,,2020,"Zhao, J. P.; Hu, Y.; Du, R. H.; Chen, Z. S.; Jin, Y.; Zhou, M.; Zhang, J.; Qu, J. M.; Cao, B.",Zhonghua Jie He He Hu Xi Za Zhi,2234990575,#480,
,CZI,Recommendations on extracorporeal life support for critically ill patients with novel coronavirus pneumonia,10.3760/cma.j.issn.1001-0939.2020.0009,,32035430,,"Along with the sharp increase of confirmed cases novel coronavirus infection, more critically ill cases require extracorporeal membrane oxygenation (ECMO) support. Based on the clinical data of novel coronavirus pneumonia (NCP), as well as the dada from previous clinical studies and the recommendations from the Extracorporeal Life Support Organization (ELSO), the committee board of the Chinese Society of Extracorporeal Life Support (CSECLS) made this recommendations to guide clinical ECMO application in the patients with NCP.",2020,"Chinese Society of Extracorporeal Life, Support",Zhonghua Jie He He Hu Xi Za Zhi,2930768960,#571,
,CZI,Respiratory support for severe 2019-nCoV pneumonia suffering from acute respiratory failure: time and strategy,10.3760/cma.j.issn.1001-0939.2020.0010,,32048501,,"Respiratory support is a very important technique for saving severe 2019-nCoV pneumonia patients who suffering respiratory failure, which can improve oxygenation, reduce mortality. Therefore, how to reasonable using respiratory support technique is the key point that relating success or failure. In this paper, the authors introduce their experience on treating severe 2019-nCoV pneumonia, it is hopeful for current fighting against 2019-nCoV in China.",2020,"Yuan, X.; Mu, J. S.; Mo, G. X.; Hu, X. S.; Yan, P.; Xie, L. X.",Zhonghua Jie He He Hu Xi Za Zhi,2878534291,#712,
,CZI,Pharmacotherapeutics for the New Coronavirus Pneumonia,10.3760/cma.j.issn.1001-0939.2020.0012,,32057209,,"The New Coronavirus Pneumonia (NCP, also named as COVID-19 by WHO on Feb 11 2020, is now causing a severe public health emergency in China since. The number of diagnosed cases is more than 40,000 until the submission of this manuscript. Coronavirus has caused several epidemic situations world widely, but the present contagious disease caused by 2019 new Coronavirus is unprecedentedly fulminating. The published cohorts of 2019 new Coronavirus (n-Cov) are single-center studies, or retrospective studies. We here share the therapeutic experiences of NCP treatment with literature review. Combination of Ribavirin and Interferon-α is recommended by the 5(th) edition National Health Commission's Regimen (Revised Edition) because of the effect on MERS (Middle East Respiratory Syndrome), and the effectiveness of Lopinavir/Ritonavir and Remdisivir needs to be confirmed by randomized controlled trial (RCT), given the situation of no specific antivirus drug on NCP is unavailable. Systemic glucocorticosteroid is recommended as a short term use (1~2 mg.kg(-1).d(-1), 3~5d ) by the 5(th) edition National Health Commission's Regimen (Revised Edition) yet RCTs are expected to confirm the effectiveness. Inappropriate application of antibiotics should be avoided, especially the combination of broad-spectrum antibiotics, for the NCP is not often complicated with bacterial infection.",2020,"Du, B.; Qiu, H. B.; Zhan, X.; Wang, Y. S.; Kang, H. Y. J.; Li, X. Y.; Wang, F.; Sun, B.; Tong, Z. H.",Zhonghua Jie He He Hu Xi Za Zhi,2780363919,#1150,
,CZI,Clinical features of 2019 novel coronavirus pneumonia in the early stage from a fever clinic in Beijing,10.3760/cma.j.issn.1001-0939.2020.0013,,32061066,,"Objective: To summarize and analyze the clinical and imaging characteristics of patients with 2019 novel coronavirus pneumonia in the early stage in Beijing. Methods: A retrospective analysis of clinical and imaging data of 9 patients with 2019 novel coronavirus infection diagnosed in one fever clinicic in Beijing from January 18, 2020 to February 3, 2020. Results: 5 male and 4 female was included in those 9 patients, whose median age was 36 years, and the age range from 15 to 49 years. 8 of these patients had no underlying disease and one suffered from diabetes. 7 patients had a history of travel to Wuhan City or Hubei Province, and one patient was a medical staff. Two family clustered was found. The incubation period was 1 to 6 days. The clinical manifestations were fever in 8 cases (8/9) , dry cough in 5 cases (5/9) , pharyngalgia in 4 cases (4/9) , fatigue in 4 cases (4/9) , body soreness in 4 cases (4/9) , and blocked or watery nose in 1 case (1/9) . Six patients (6/9) had abnormal cell peripheral blood, of which 3 (3/9) had an increased monocyte count, 2 (2/9) had a reduced lymphocyte , and 1 (1/9) had an increased leukocyte count, while the 3 patients had normal cell blood routines. The median of CRP was 16.3 mg/L, including 5 patients with slightly elevated (5/9) , 4 patients with normal values (4/9) . the results of procalcitonin test were negative in5 patients. Three patients were examined by chest X-ray examination, one of which was normal, one case showed infiltrates of right upper lung, and another showed in right lower lung. All patients underwent chest HRCT. And 7 cases (7/9) showed multiple ground glass exudation, including 5 cases (5/7) involved bilateral lungs, 2 cases (2/7) involved unilateral lung, 3 cases (3/7) with patchy consolidation, and 2 cases (2/9) showed no abnormality. Conclusions: The patents with 2019 novel coronavirus pneumonia in this study generally have an epidemiological history. The clinical manifestations are fever and cough. Peripheral white blood cell counts were most normal And PCT were all negative. Chest HRCT manifested as multiple ground-glass opacities with partly consolidation. Some patients had normal chest radiographs but HRCT showed pneumonia. Some patients had no pneumonia on chest HRCT.",2020,"Zhang, M. Q.; Wang, X. H.; Chen, Y. L.; Zhao, K. L.; Cai, Y. Q.; An, C. L.; Lin, M. G.; Mu, X. D.",Zhonghua Jie He He Hu Xi Za Zhi,3006640104,#891,
,CZI,Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia,10.3760/cma.j.issn.1001-0939.2020.0014,,32061198,,"The novel coronavirus 2019 (COVID-19) infected patients by binding human ACE2, leading to severe pneumonia and highly mortality rate in patients. At present, there is no definite and effective treatment for COVID-19. ACE2 plays an important role in the RAS, and the imbalance between ACE/Ang II/AT1R pathway and ACE2/Ang (1-7)/Mas receptor pathway in the RAS system will lead to multi-system inflammation. Increased ACE and Ang II are poor prognostic factors for severe pneumonia. Animal studies have shown that RAS inhibitors could effectively relieve symptoms of acute severe pneumonia and respiratory failure. The binding of COVID-19 and ACE2 resulted in the exhaustion of ACE2, and then ACE2/Ang (1-7)/Mas receptor pathway was inhibited. The balance of the RAS system was broken, and this would lead to the exacerbation of acute severe pneumonia. Therefore, we speculate that ACEI and AT1R inhibitors could be used in patients with COVID-19 pneumonia under the condition of controlling blood pressure, and might reduce the pulmonary inflammatory response and mortality.",2020,"Sun, M. L.; Yang, J. M.; Sun, Y. P.; Su, G. H.",Zhonghua Jie He He Hu Xi Za Zhi,3006039930,#912,
,CZI,Conventional respiratory support therapy for Severe Acute Respiratory Infections (SARI): Clinical indications and nosocomial infection prevention and control,10.3760/cma.j.issn.1001-0939.2020.0015,,32061199,,"Severe acute respiratory infection (SARI) diseases (such as SARS, MERS, pH1N1) can rapidly progress to acute respiratory failure with high lethality. The outbreak of a novel coronavirus infection can lead to 15% ~ 30% patients developing into acute respiratory distress syndrome (ARDS). Respiratory support is the most important therapy for SARI patients with respiratory failure. However, respiratory support is a high skilled technology, which means inappropriate application may bring related complications and cross infection of SARI pathogens among medical staff and non-medical personnel in hospital. Therefore, it is meaningful to established a standardized indication of respiratory support and to prevent related nosocomial transmission in SARI patients.",2020,"Critical care committee of Chinese Association of Chest, Physician; Respiratory; critical care group of Chinese Thoracic, Society; Respiratory care group of Chinese Thoracic, Society",Zhonghua Jie He He Hu Xi Za Zhi,2937860957,#985,
,CZI,Clinical characteristics of 30 medical workers infected with new coronavirus pneumonia,10.3760/cma.j.issn.1001-0939.2020.0016,,32062957,,"Objective: To investigate the clinical characteristics of medical staff with novel coronavirus pneumonia(NCP). Methods: 30 patients infected with novel coronavirus referred to jianghan university hospital between January 11, 2020 and January 3, 2020 were studied. The data reviewed included those of clinical manifestations, laboratory investigation and Radiographic features. Results: The patients consisted of 10 men and 20 women, including 22 doctors and 8 nurses,aged 21~59 years(mean 35±8 years).They were divided to 26 common type and 4 severe cases, all of whom had close(within 1m) contact with patients infected of novel coronavirus pneumonia. The average contact times were 12 (7,16) and the average cumulative contact time was 2 (1.5,2.7) h.Clinical symptoms of these patients were fever in 23 patients (76.67%) , headache in 16 petients (53.33%) , fatigue or myalgia in 21patients (70%) , nausea, vomiting or diarrhea in 9 petients (30%) , cough in 25 petients (83.33%) , and dyspnea in 14 petients (46.67%) .Routine blood test revealed WBC <4.0×10(9)/L in 8 petients (26.67%) , (4-10) ×10(9)/L in 22 petients (73.33%) , and WBC>4.0×10(9)/L in 4 petients (13.33%) during the disease.Lymphocyte count <1.0×10(9)/L occurred in 12 petients (40%),abnormal liver function in 7 petients (23.33%) ,myocardial damage in 5 petients(16.67%), elevated D-dimer (>0.5mg/l) in 5 patients (16.67%). Compared with normal patients, the average exposure times, cumulative exposure time, BMI, Fever time, white blood cell count, liver enzyme, LDH, myoenzyme and D-dimer were significantly increased in severe patients, while the lymphocyte count and albumin levels in peripheral blood were significantly decreased.Chest CT mainly showed patchy shadows and interstitial changes.According to imaging examination, 11 patients (36.67%) showed Unilateral pneumonia and 19 patients (63.33%) showed bilateral pneumonia,4 patients (13.33%) showed bilateral multiple mottling and ground-glass opacity.Compared with the patients infected in the protected period, the proportion of severe infection and bilateral pneumonia were both increased in the patients infected in unprotected period. Conclusion: Medical staffs are at higher risk of infection.Infection rates are associated with contact time, the amount of suction virus. Severe patients had BMI increased, heating time prolonged , white blood cell count, lymphocyte count, D-dimer and albumin level significantly changed and were prone to be complicated with liver damage and myocardial damage.Strict protection measures is important to prevent infection for medical workers.",2020,"Liu, M.; He, P.; Liu, H. G.; Wang, X. J.; Li, F. J.; Chen, S.; Lin, J.; Chen, P.; Liu, J. H.; Li, C. H.",Zhonghua Jie He He Hu Xi Za Zhi,3005079553,#1008,
,CZI,Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia,10.3760/cma.j.issn.1001-0939.2020.0019,,32075365,,"At the end of December 2019, a novel coronavirus (COVID-19) caused an outbreak in Wuhan, and has quickly spread to all provinces in China and 26 other countries around the world, leading to a serious situation for epidemic prevention. So far, there is still no specific medicine. Previous studies have shown that chloroquine phosphate (chloroquine) had a wide range of antiviral effects, including anti-coronavirus. Here we found that treating the patients diagnosed as novel coronavirus pneumonia with chloroquine might improve the success rate of treatment, shorten hospital stay and improve patient outcome. In order to guide and regulate the use of chloroquine in patients with novel coronavirus pneumonia, the multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia developed this expert consensus after extensive discussion. It recommended chloroquine phosphate tablet, 500mg twice per day for 10 days for patients diagnosed as mild, moderate and severe cases of novel coronavirus pneumonia and without contraindications to chloroquine.",2020,"multicenter collaboration group of Department of, Science; Technology of Guangdong, Province; Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus, pneumonia",Zhonghua Jie He He Hu Xi Za Zhi,3004896587,#1543,
,CZI,Expert consensus on preventing nosocomial transmission during respiratory care for critically ill patients infected by 2019 novel coronavirus pneumonia,10.3760/cma.j.issn.1001-0939.2020.0020,,32077661,,"Definite evidence has shown that the novel coronavirus (COVID-19) could be transmitted from person to person, so far more than 1,700 bedside clinicians have been infected. A lot of respiratory treatments for critically ill patients are deemed as high-risk factors for nosocomial transmission, such as intubation, manual ventilation by resuscitator, noninvasive ventilation, high-flow nasal cannula, bronchoscopy examination, suction and patient transportation, etc, due to its high possibility to cause or worsen the spread of the virus. As such, we developed this consensus recommendations on all those high-risk treatments, based on the current evidence as well as the resource limitation in some areas, with the aim to reduce the nosocomial transmission and optimize the treatment for the COVID-19 pneumonia patients. Those recommendations include: (1) Standard prevention and protection, and patient isolation; (2) Patient wearing mask during HFNC treatment; (3) Using dual limb ventilator with filters placed at the ventilator outlets, or using heat-moisture exchanger (HME) instead of heated humidification in single limb ventilator with HME placed between exhalation port and mask; avoid using mask with exhalation port on the mask; (4) Placing filter between resuscitator and mask or artificial airway; (5) For spontaneous breathing patients, placing mask for patients during bronchoscopy examination; for patients receiving noninvasive ventilation, using the special mask with bronchoscopy port to perform bronchoscopy; (6) Using sedation and paralytics during intubation, cuff pressure should be maintained between 25-30 cmH(2)O; (7) In-line suction catheter is recommended and it can be used for one week; (8) Dual-limb heated wire circuits are recommended and only changed with visible soiled; (9. For patients who need breathing support during transportation, placing an HME between ventilator and patient; (10) PSV is recommended for implementing spontaneous breathing trial (SBT), avoid using T-piece to do SBT. When tracheotomy patients are weaned from ventilator, HME should be used, avoid using T-piece or tracheostomy mask. (11) Avoid unnecessary bronchial hygiene therapy; (12) For patients who need aerosol therapy, dry powder inhaler metered dose inhaler with spacer is recommended for spontaneous breathing patients; while vibrating mesh nebulizer is recommended for ventilated patients and additional filter is recommended to be placed at the expiratory port of ventilation during nebulization.",2020,"Respiratory care committee of Chinese Thoracic, Society",Zhonghua Jie He He Hu Xi Za Zhi,2110407084,#1510,
,CZI,The prevention and control of a new coronavirus infection in department of stomatology,10.3760/cma.j.issn.1002-0098.2020.0001,,32057210,,"During a short period of time, the outbreak of pneumonia caused by a novel coronavirus, named Novel Coronavirus Pneumonia (NCP), was first reported in China, spreading to 24 countries and regions rapidly. The number of confirmed cases and deaths continued to rise. World Health Organization (WHO) announced that the outbreaks of the novel coronavirus have constituted a Public Health Emergency of International Concern. Efficient infection control can prevent the virus from further spreading, which makes the epidemic situation under control. Due to the specialty of oral healthcare settings, the risk of cross infection is severe among patients and oral healthcare practitioners. It's more urgent to implement strict and efficient infection control protocols. This paper, based on existing guidelines and published researches pertinent to dental infection-control principles and practices, mainly discusses epidemiological characteristics of NCP and the features of nosocomial infection in oral healthcare settings, and furthermore provides recommendations on patient's evaluation, and infection control protocols in department of stomatology under current circumstance..",2020,"Li, Z. Y.; Meng, L. Y.",Zhonghua Kou Qiang Yi Xue Za Zhi,2377782053,#1228,
,CZI,Management and clinical thinking of Coronavirus Disease 2019,10.3760/cma.j.issn.1007-3418.2020.0002,,32125126,,"In December 2019, the 2019 novel coronavirus pneumonia (NCP, officially named Coronavirus Disease 2019(COVID-19) by the World Health Organization) broke out in Wuhan, Hubei, and it quickly spread to the whole country and abroad. The situation was at stake. The sudden and serious COVID-19 epidemic has brought us a lot of urgent problems. How to effectively control the spread of COVID-19? When does the population infection rate rise to its peak? What will eventually be the number of infected patients? How to make early diagnosis? What effective antiviral drugs are available? How to effectively treat with existing drugs? Can it successfully improve the survival rate of critically patients? In response to the above questions, we put forward corresponding suggestions and reflections from the perspective of the infectious clinician.",2020,"Ma, K.; Chen, T.; Han, M. F.; Guo, W.; Ning, Q.",Zhonghua Gan Zang Bing Za Zhi,2895837418,#3337,
,CZI,Novel coronavirus pneumonia related liver injury: etiological analysis and treatment strategy,10.3760/cma.j.issn.1007-3418.2020.02.001,,32075364,,"The outbreak of novel coronavirus pneumonia(NCP) caused by 2019 novel coronavirus has become a global public health challenge. Some patients accompany with liver function damage in addition to the main typical respiratory symptom. Here we analyzed the clinical features, susceptible population, potential causes and therapeutic strategies of NCP related liver injury.",2020,"Hu, L. L.; Wang, W. J.; Zhu, Q. J.; Yang, L.",Zhonghua Gan Zang Bing Za Zhi,2076942479,#2261,
,CZI,Exploring the mechanism of liver enzyme abnormalities in patients with novel coronavirus-infected pneumonia,10.3760/cma.j.issn.1007-3418.2020.02.002,,32077659,,"Objective: To explore and analyze the possible mechanism of liver injury in patients with coronavirus disease 2019 (novel coronavirus pneumonia, NCP). Methods: The correlation between ALT, AST and other liver enzyme changes condition and NCP patients' disease status reported in the literature was comprehensively analyzed. ACE2 expression in liver tissue for novel coronavirus was analyzed based on single cell sequencing (GSE115469) data. RNA-Seq method was used to analyze Ace2 expression and transcription factors related to its expression in liver tissues at various time-points after hepatectomy in mouse model of acute liver injury with partial hepatectomy. t-test or Spearman rank correlation analysis was used for statistical analysis. Results: ALT and AST were abnormally elevated in some patients with novel coronavirus infection, and the rate and extent of ALT and AST elevation in severe NCP patients were higher than those in non-severe patients. Liver tissue results of single cell sequencing and immunohistochemistry showed that ACE2 was only expressed in bile duct epithelial cells of normal liver tissues, and very low in hepatocytes. In a mouse model of acute liver injury with partial hepatectomy, Ace2 expression was down-regulated on the first day, but it was elevated up to twice of the normal level on the third day, and returned to normal level on seventh day when the liver recovered and hepatocyte proliferation stopped. Whether this phenomenon suggests that the bile duct epithelial cells with positive expression of Ace2 participate in the process of liver regeneration after partial hepatectomy deserves further study. In RNA-Seq data, 77 transcription factors were positively correlated with the expression of ACE2 (r > 0.2, FDR < 0.05), which were mainly enriched in the development, differentiation, morphogenesis and cell proliferation of glandular epithelial cells. Conclusion: We assumed that in addition to the over activated inflammatory response in patients with NCP, the up-regulation of ACE2 expression in liver tissue caused by compensatory proliferation of hepatocytes derived from bile duct epithelial cells may also be the possible mechanism of liver tissue injury caused by 2019 novel coronavirus infection.",2020,"Guan, G. W.; Gao, L.; Wang, J. W.; Wen, X. J.; Mao, T. H.; Peng, S. W.; Zhang, T.; Chen, X. M.; Lu, F. M.",Zhonghua Gan Zang Bing Za Zhi,2006335368,#1637,
,CZI,Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study,10.3760/cma.j.issn.1007-3418.2020.02.003,,32077660,,"Objective: To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage. Methods: Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate. Results: 32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34- ~ 21.15) mmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31- ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) mmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) mmol/L, respectively. Conclusion: The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.",2020,"Liu, C.; Jiang, Z. C.; Shao, C. X.; Zhang, H. G.; Yue, H. M.; Chen, Z. H.; Ma, B. Y.; Liu, W. Y.; Huang, H. H.; Yang, J.; Wang, Y.; Liu, H. Y.; Xu, D.; Wang, J. T.; Yang, J. Y.; Pan, H. Q.; Zou, S. Q.; Li, F. J.; Lei, J. Q.; Li, X.; He, Q.; Gu, Y.; Qi, X. L.",Zhonghua Gan Zang Bing Za Zhi,2564157091,#1567,
,CZI,Treatment strategy for gastrointestinal tumor under the outbreak of novel coronavirus pneumonia in China,10.3760/cma.j.issn.1671-0274.2020.02.001,,32074786,,"The outbreak of the novel coronavirus pneumonia (NCP) has become a public health emergency in China. Chinese authorities and health agencies had devoted great efforts to control this disease. As surgeons specialized in the treatment of gastrointestinal tumors, we should always be aware of the prevention for NCP and incorporate this awareness into every detail of clinical practice. For the patients with gastrointestinal tumors, pre-admission screening should be done in order to rule out NCP. Real-time RT-PCR panel and chest CT scan should be conducted for patients with fever (>37.3℃), travel history to Hubei Province within 14 days, or contact history with residents from Wuhan district within 14 days. Prevention measures for both medical staffs and the screen-negative admitted patients should also be enhanced because false negative is possible. Medical instruments should be properly discarded or disinfected according to standardized procedures established by the local center for disease control and prevention (CDC). Surgical operation should be reduced at a minimal level to prevent cross infection in this special period.Surgical intervention for benign tumor should be postponed. For malignant tumor, multidisciplinary therapy (MDT) is recommended and non-surgical anti-tumor therapy should be selected with higher priority. Neoadjuvant therapy is highly recommended for gastrointestinal cancer at advanced stages that meet the indications of NCCN guideline (gastric cancer T stage ≥ 2/rectal cancer T stage ≥ 3/unresectable colon cancer). Gastric or esophagogastricjunction (EGJ) malignant tumor with obstruction can be managed with gastric tube decompression or stent placement to relieve the symptoms. Transnasal enteral feeding tube intubation/percutaneous endoscopic gastrostomy could be adopted to ensure enteral nutrition supply. For colorectal malignancy with simple intestinal obstruction, stent placement can achieve a high success rate, which not only helps avoid emergency surgery, but also creates a better condition for subsequent surgery. Transcatheter arterial embolization for hemostasis is an alternative choice for gastrointestinal tumor with bleeding. However, emergency operation still must be performed for patients with acute uncontrolled bleeding, obstruction or after other alternative treatment measures fail. All cases with suspicious or confirmed with NCP must be reported to the local CDC department. All invasive intervention must be performed in a designated isolation area. Tertiary prevention measure must be adopted for all anesthetists with additional face mask or medical goggle protection to prevent respiratory droplet transmission. Preventive enterostomy is preferable in lower digestive tract surgery. Thoroughly disinfecting the operating room after surgery is necessary. Fever after surgery must be carefully differentiated whether it's caused by post-surgery abdominal infection/inflammation or NCP. Single-room isolation and related examinations should be performed according to the standard procedures. We believe that with the unprecedentedly joint efforts of doctors and patients, we will eventually win this war against NCP.",2020,"Chen, Y. H.; Peng, J. S.",Zhonghua Wei Chang Wai Ke Za Zhi,2606110885,#2332,
,CZI,Several suggestion of operation for colorectal cancer under the outbreak of Corona Virus Disease 19 in China,10.3760/cma.j.issn.1671-0274.2020.03.002,,32074719,,"Pneumonia caused by SARS-Cov-2 infection has been reported in Wuhan since December 2019, and spread rapidly across the country. The radical operation of colorectal cancer is confine operation. Patients with colorectal cancer should receive operation as soon as possible after elective operation is resumed in each hospital. SARS-Cov-2 virus can be transmitted by asymptomatic infectors, and it has been confirmed to be transmitted by droplets and contact. However, fecal-oral transmission and aerosol transmission have not been excluded. Based onLaparoscopic colorectal operation experiences, the author suggests that the surgery strategy for colorectal cancer patients under the COVID-19 situation. Recommending laparoscopy-assisted radical surgery for colorectal cancer patients. The aerosols need to be strictly managed during operation. NOSES and TaTME should be carried out with cautious during the epidemic period. Protective stoma should be carried out scientifically and reasonably, and the protection of operating room personnel should be strengthened.",2020,"Yu, G. Y.; Lou, Z.; Zhang, W.",Zhonghua Wei Chang Wai Ke Za Zhi,2086544875,#1438,
,CZI,Suggestions for prevention of 2019 novel coronavirus infection in otolaryngology head and neck surgery medical staff,10.3760/cma.j.issn.1673-0860.2020.0001,,32023680,,"The epidemic of the 2019 Novel Coronavirus (2019-nCoV) infection has presented as a grim and complex situation recently. More than 11,000 cases of 2019-nCoV infection has been confirmed in China until February 1(st) 2020, which are causing great impact to economy and society, and seriously interfering with ordinary medical practice of otolaryngology and head and neck surgery. This advice guideline discusses the medical protection measures required in the outpatient clinic as well as in operation ward in otolaryngology head and neck department, which aims to protect medical staff from 2019-nCoV infection.",2020,"Xu, K.; Lai, X. Q.; Liu, Z.",Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi,3004896587,#254,
,CZI,Airway management of COVID-19 patients with severe pneumonia,10.3760/cma.j.issn.1673-0860.2020.04.001,,32100976,,"Patients with severe and critical COVID-19 will develop into acute respiratory distress syndrome in a short time. Noninvasive or invasive positive pressure ventilation will be important means for those patients, which will help to improve the clinical cure rate and reduce the mortality. Effective airway management has a great significance to improve respiratory support, reduce complications, and promote rehabilitation.",2020,,Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi,2974894063,#2471,
,CZI,Thinking on Clinical rational use of TCM injection in the treatment of novel coronavirus pneumonia (COVID-19),10.3760/cma.j.issn.cn112137-20200221-00388,,32122113,,,2020,"Wang, Z. F.; Wang, Y. P.; Zhang, H. M.; Fan, Y. P.; Lü, C.; Wang, Y. Y.",Zhonghua Yi Xue Za Zhi,1542898014,#3277,
,CZI,Cardiac manifestations of patients with COVID-19 pneumonia and related treatment recommendations,10.3760/cma.j.issn.cn112148-20200213-00077,,32118392,,引起2002年严重急性呼吸综合征(SARS)和2012年中东呼吸综合征(MERS)的冠状病毒(CoV)被证实是从动物传播至人类的。而2019新型 冠状病毒(2019-nCov)引起了新型冠状病毒肺炎的暴发,则再次证明CoV对人类健康具有重大的威胁。2019-nCov除感染呼吸系统外,研究报 道其对心血管系统也有侵害作用。本文对2019-nCov的基因组结构、功能以及感染者的病理生理学和心脏表型特征、心脏损伤的潜在机制、相关治疗策略进 行了梳理,警示临床医生注意2019-nCov对心脏的潜在风险、加强心脏功能管理。.,2020,"Tan, Z. C.; Fu, L. H.; Wang, D. D.; Hong, K.",Zhonghua xin xue guan bing za zhi,2999536665,#3988,
,CZI,Myocardial injury in patients with COVID-19 pneumonia,10.3760/cma.j.issn.cn112148-20200220-00106,,32118393,,自2019年12月以来,中国湖北省开始出现了2019新型冠状病毒(2019-nCoV)感染疫情并逐渐扩散至其他省份乃至其他国家。该病毒具有传播能 力强、临床表现多样、潜伏期长、可隐性传染等特征,对人类生命安全和健康造成严重威胁。随着病例数的不断增加和临床资料的不断丰富,2019-nCoV感 染患者除了典型的呼吸系统表现外,与病毒感染相关的心肌损伤情况逐渐受到重视。根据已公布的资料,我们总结了目前已知的2019-nCoV感染患者的心肌 损伤表现、特征、对病情及预后的影响,并对可能的损伤机制、治疗方法以及未来的研究方向作一论述。.,2020,"Wei, Z. Y.; Qian, H. Y.",Zhonghua xin xue guan bing za zhi,2365550483,#4193,
,CZI,Preliminary Recommendations for Lung Surgery during SARS-CoV-2 Novel Coronavirus Pneumonia Epidemic Period,10.3779/j.issn.1009-3419.2020.03.01,,32077440,,"In December 2019, China diagnosed the first patient with novel coronavirus pneumonia, and the following development of the epidemic had a huge impact on China and the whole world. For patients with lung occupying lesions, the whole process of diagnosis and treatment can not be carried out as usual due to the epidemic. For thoracic surgeons, the timing of surgical intervention should be very carefully considered. All thoracic surgeons in China should work together to develop the proper procedures for the diagnosis and treatment in this special situation, and continuously update the recommendations based on epidemic changes and further understanding of new coronavirus pneumonia. Here, we only offer some preliminary suggestions based on our own knowledge for further reference and discussion.",2020,"Li, Xin; Liu, Minghui; Zhao, Qingchun; Liu, Renwang; Zhang, Hongbing; Dong, Ming; Xu, Song; Zhao, Honglin; Wei, Sen; Song, Zuoqing; Chen, Gang; Chen, Jun",Zhongguo Fei Ai Za Zhi,3005538648,#1583,
,CZI,Clinical Management of Lung Cancer Patients during the Outbreak of 2019 Novel Coronavirus Disease (COVID-19),10.3779/j.issn.1009-3419.2020.03.02,,32077441,,"Since late December 2019, an outbreak of 2019 novel coronavirus diseases (COVID-19) in Wuhan, China has spread quickly nationwide. With the spread of COVID-19, the routine clinical diagnosis and treatment for lung cancer patients has been disturbed. Due to the systemic immunosuppressive of lung cancer patients caused by the malignancy and anticancer treatments, lung cancer patients are more susceptible to infection than healthy individuals. Furthermore, patients with cancer had poorer prognosis from infection. Lung cancer patients should be the priority group for COVID-19 prevention. The protection provisions and control measures aiming to protect lung cancer patients from COVID-19 have been increasingly concerned. During the COVID-19 outbreak period, it should be carefully differentiated for fever and respiratory symptoms for lung cancer patients receiving anti-tumor treatment, in order to evaluate the risk of COVID-19. Moreover, it is necessary to carry out meticulous and individualized clinical management for lung cancer patients to effectively protect the patients from COVID-19.",2020,"Xu, Yan; Liu, Hongsheng; Hu, Ke; Wang, Mengzhao",Zhongguo Fei Ai Za Zhi,2907814135,#1445,
,CZI,A Chinese Case of COVID-19 Did Not Show Infectivity During the Incubation Period: Based on an Epidemiological Survey,10.3961/jpmph.20.048,,32114755,,Controversy remains over whether the novel coronavirus 2019 (COVID-19) virus may have infectivity during the incubation period before the onset of symptoms. The author had the opportunity to examine the infectivity of COVID-19 during the incubation period by conducting an epidemiological survey on a confirmed patient who had visited Jeju Island during the incubation period. The epidemiological findings support the claim that the COVID-19 virus does not have infectivity during the incubation period.,2020,"Bae, Jong-Myon",J Prev Med Public Health,2029228287,#3073,
,CZI,Small Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Fusion by Targeting Cavities on Heptad Repeat Trimers,10.4062/biomolther.2019.202,,32126736,,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a newly emerging viral disease with fatal outcomes. However, no MERS-CoV-specific treatment is commercially available. Given the absence of previous structure-based drug discovery studies targeting MERS-CoV fusion proteins, this set of compounds is considered the first generation of MERS-CoV small molecule fusion inhibitors. After a virtual screening campaign of 1.56 million compounds followed by cell-cell fusion assay and MERS-CoV plaques inhibition assay, three new compounds were identified. Compound numbers 22, 73, and 74 showed IC(50) values of 12.6, 21.8, and 11.12 µM, respectively, and were most effective at the onset of spike-receptor interactions. The compounds exhibited safe profiles against Human embryonic kidney cells 293 (HEK293) at a concentration of 20 µM with no observed toxicity in Vero cells at 10 µM. The experimental results are accompanied with predicted favorable pharmacokinetic descriptors and drug-likeness parameters. In conclusion, this study provides the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range.",2020,"Kandeel, Mahmoud; Yamamoto, Mizuki; Al-Taher, Abdulla; Watanabe, Aya; Oh-Hashi, Kentaro; Park, Byoung Kwon; Kwon, Hyung-Joo; Inoue, Jun-Ichiro; Al-Nazawi, Mohammed",Biomol Ther (Seoul),2139603860,#4352,
,CZI,Emergent Strategies for the Next Phase of COVID-19,10.4088/JCP.08m04485blu,,32100487,,,2020,"Huh, Kyungmin; Shin, Hyoung Shik; Peck, Kyong Ran",Infect Chemother,2071972290,#2255,
,CZI,Imported cases of 2019-novel coronavirus (2019-nCoV) infections in Thailand: Mathematical modelling of the outbreak,10.4103/1995-7645.277516,,,,"Imported cases of 2019-novel coronavirus (2019-nCoV) infections in Thailand: Mathematical modelling of the outbreak' in DOAJ. DOAJ is an online directory that indexes and provides access to quality open access, peer-reviewed journals.",2020,"Wiwanitkit, Pathum Sookaromdee; Viroj",Asian Pacific Journal of Tropical Medicine,3005391564,#2516,
,CZI,Emerging and re-emerging human infectious diseases: A systematic review of the role of wild animals with a focus on public health impact,10.4103/1995-7645.277535,,,,"Infectious diseases continue to impose unpredictable burdens on global health and economies, a subject that requires constant research and updates. In this sense, the objective of the present article was to review studies on the role of wild animals as reservoirs and/or dispersers of etiological agents of human infectious diseases in order to compile data on the main wild animals and etiological agents involved in zoonotic outbreaks. A systematic review was carried out using PRISMA guidelines, using the PubMed, Scopus and SciELO platforms as data banks. The descriptors used were “zoonosis”, “human infectious diseases” and “wild animals”. The results show that wild animals (mainly bats, birds and primates) play an important role in the dissemination of etiological agents (mainly viruses, as a new coronavirus called 2019 Novel Coronavirus) in extensive geographic regions. Moreover, these wild animal organisms can act as the site for essential biotic synergy among several pathogenic microorganisms, promoting a higher rate of adaptation, mutation and even genetic recombination, with consequent stimulation of new strains and subtypes, inducing new infectious agents with unknown virulent potential. In conclusion, the monitoring of these diseases and adequate preparation for possible epidemics and pandemics are fundamental conditions for the mitigation of their future impact. The zoonotic threat of these etiological agents and the impact on public health can be enormous as shown by the ongoing epidemic of 2019 novel coronavirus (2019- nCoV) infections.",2020,"Siqueira-Batista, Marli C. Cupertino; Michely, B. Resende; Nicholas, A. J. Mayer; Lorendane, M. Carvalho; Rodrigo",Asian Pacific Journal of Tropical Medicine,3004810054,#2543,
,CZI,Novel coronavirus (2019-nCoV) update: What we know and what is unknown,10.4103/1995-7645.277795,,,,"Preliminary clinical features indicated that most of the infected patients were men with underlying diseases (comorbidities) including diabetes, hypertension, cardiovascular disease, chronic obstructive pulmonary disease, malignancy and chronic liver disease[6]. Patient presented with fever, cough, myalgia, sputum production, headache, haemoptysis, diarrhea and dyspnea[6]. Person- to-person transmission and familiar association have also been confirmed[7]. To date, a diagnostic kit has been developed for 2019- nCoV[8], and efforts are ongoing to develop other protocols. Whilst several important aspects of 2019-nCoV epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, have been defined, there remain many unanswered questions, including source, transmission and epidemic potential. The Wuhan outbreak is a stark reminder of the continuing threat of zoonotic diseases.",2020,"Fasina, Folorunso Oludayo",Asian Pacific Journal of Tropical Medicine,3004467862,#2646,
,CZI,Dose prediction of lopinavir/ritonavir for 2019-novel coronavirus (2019-nCoV) infection based on mathematic modeling,10.4103/1995-7645.277815,,,,"At present, lopinavir/ritonavir is widely used for possible treatment of 2019-nCoV infection in countries that the emerging infection exists. Here, the authors used a mathematical modelling theoretical approach to predict the expectedproper dosage of lopinavir/ritonavir for possible treatment of 2019-nCoV infection. The protocol for mathematical modeling in this work is the same as previous report by Wiwanitkit et al[5]. Briefly, the primary agreement was there had to be a specific amount of required energy for reaction between lopinavir/ritonavir and its target enzyme and this energy is a specific constant for the reaction. Based on bonding theory, the required amount of lopinavir/ritonavir was varied to the two substrates, lopinavir/ritonavir and target, protease. Here, the simple equation ‘A + B ? C where A was the target enzyme, B was lopinavir/ritonavir and C was end product’ could be written.",2020,"Wiwanitkit, Sora Yasri; Viroj",Asian Pacific Journal of Tropical Medicine,3006177842,#2515,
,CZI,Epidemiologic characteristics of early cases with 2019 novel coronavirus (2019-nCoV) disease in Republic of Korea,10.4178/epih.e2020007,,32035431,,"Since the first case of 2019 novel coronavirus (2019-nCoV) in South Korea was confirmed on January 20, 2020, there have been 24 confirmed cases of 2019-nCoV. The majority of these cases (58.3%; n=14) were male, with a median age of 42 years (range, 21-62 years). Of the confirmed cases, 15 were index cases (63%), six were first-generation patients (24%), and three were second-generation patients (12.5%). All the first- and second-generation patients were family members or close acquaintances of index cases. All the index cases entered the South Korea from January 19 to 24, 2020. The average incubation period was 3.6 days (median, 4 days) and the reproduction number (R0) was calculated as 0.5. Two of the confirmed cases were asymptomatic. As of February 8, 22 patients with 2019-nCoV are hospitalized in South Korea, and 2 have been discharged from the hospital. The epidemiological indicators will be revised as new information becomes available in the future. Sharing epidemiological information among researchers around the world is essential for efficient preparations and responses to new infectious diseases.",2020,"Ki, Moran; nCoV, Task Force For",Epidemiol Health,3006364226,#567,
,CZI,Understanding COVID-19 new diagnostic guidelines - a message of reassurance from an internal medicine doctor in Shanghai,10.4414/smw.2020.20216,,32134111,,,2020,"Bischof, E.; Chen, G.; Ferretti, M. T.",Swiss medical weekly,2073887351,#5063,
,CZI,Drug treatment options for the 2019-new coronavirus (2019-nCoV),10.5582/bst.2020.01020,,,,,2020,"Lu, Hongzhou","BioScience TrendsAB - As of January 22, 2020, a total of 571 cases of the 2019-new coronavirus (2019-nCoV) have been reported in 25 provinces (districts and cities) in China. At present, there is no vaccine or antiviral treatment for human and animal coro",3003322996,#55,
,CZI,Efficacies of lopinavir/ritonavir and abidol in the treatment of novel coronavirus pneumonia,10.5582/bst.2020.01030,,,,"Objective To evaluate the efficacies of lopinavir/ritonavir and abidol in the treatment of NCP. Methods The clinical data of 134 patients with NCP receiving treatment at Shanghai Public Health Clinical Center during Jan 20 to Feb 6, 2020 were retrospectively collected. All the patients received interferon-α2b spray and symptomatic supportive treatment, and 52 cases received oral lopinavir/ritonavir treatment, 34 cases received oral abidol treatment, the remaining 48 cases did not take any antiviral drugs. The efficacies at median day 7 among the three groups were compared by using Kruskal-Wallis or chi-square tests. Results The 134 patients included 69 males (51.5%) and 65 females, aged 35-62 years with the average of 48 years. The median time to temperature normalization in patients receiving abidol or lopinavir/ritonavir treatment was both 6 days after admission, and that was 4 days in the control group, with no significant difference ( χ 2 = 2.37, P =0.31). The median time to PCR negative in the respiratory specimens in the three groups was all 7 days after admission, and the PCR negative rates at day 7 after admission in lopinavir/ritonavir, abidol and control groups were 71.8% (28/39), 82.6% (19/23) and 77.1% (27/35), respectively, which were not significantly different ( χ 2 = 0.46 , P =0.79). Radiological worsening at day 7 was observed in comparable proportions of patients in the three groups, which were 42.3% ( n =22), 35.3% ( n =12) and 52.1% ( n =25), respectively ( χ 2 = 2.38, P =0.30) . Adverse reactions occurred in 17.3% ( n =9), 8.8% ( n =3) and 8.3% ( n =4) patients, respectively in the three groups ( χ 2 = 2.33, P =0.33). Conclusions This study did not find any effects of lopinavir/ritonavir and abidol on relieving symptoms or accelerating virus clearance. The efficacies of these two drugs in NCP treatment need further investigation.",2020,"CHEN, Jun; LING, Yun; XI, Xiuhong; LIU, Ping; LI, Feng; LI, Tao; SHANG, Zhiyin; WANG, Mei; SHEN, Yinzhong; LU, Hongzhou",Chinese Journal of Infectious Diseases,3004517278,#2339,
,CZI,Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment,10.5582/bst.2020.01030,,,,,2020,"Wang, Zhenwei; Chen, Xiaorong; Lu, Yunfei; Chen, Feifei; Zhang, Wei",BioScience Trends,3004517278,#549,
,CZI,Challenges to the system of reserve medical supplies for public health emergencies: reflections on the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in China,10.5582/bst.2020.01043,,32062645,,"On December 31, 2019, the Wuhan Municipal Health Commission announced an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), China is now at a critical period in the control of the epidemic. The Chinese Government has been taking a series of rapid, comprehensive, and effective prevention and control measures. As the pandemic has developed, a fact has become apparent: there is a serious dearth of emergency medical supplies, and especially an extreme shortage of personal protective equipment such as masks and medical protective clothing. This is one of the major factors affecting the progress of epidemic prevention and control. Although China has made great efforts to strengthen the ability to quickly respond to public health emergencies since the SARS outbreak in 2003 and it has clarified requirements for emergency supplies through legislation, the emergency reserve supplies program has not been effectively implemented, and there are also deficiencies in the types, quantity, and availability of emergency medical supplies. A sound system of emergency reserve supplies is crucial to the management of public health emergencies. Based on international experiences with pandemic control, the world should emphasize improving the system of emergency reserve medical supplies in the process of establishing and improving public health emergency response systems, and it should promote the establishment of international cooperative programs to jointly deal with public health emergencies of international concern in the future.",2020,"Wang, Xu; Zhang, Xiaoxi; He, Jiangjiang",Biosci Trends,3006332573,#1005,
,CZI,Recommendations on the pediatric flexible bronchoscopy during the outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in China (Trial Edition),10.5582/bst.2020.01043,,,,"An outbreak of pneumonia caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)infection has spread to children.Due to its strong infectivity, people are generally susceptible, including children.The main source of infection is the SARS-CoV-2 infection patients, asymptomatic infection may also become the source of infection. Bronchoscopy is a high-risk operation since during the procedure, with children & prime's coughing and an open airway, a huge number of droplets and secretions are produced, which will contaminate the desktop, equipment and air, and even infect medical staff, other children and caregivers in close contact.For this reason, experts were specially organized to write recommendations on the diagnosis and treatment of pediatric flexible bronchoscopy during the epidemic period of SARS-CoV-2 infection (trial version), establish indications and prevention and control plans of pediatric bronchoscopy during the epidemic period, and provide a basis for medical staff engaged in pediatric bronchoscopy.",2020,,Chinese Journal of Applied Clinical Pediatrics,3006332573,#1876,
,CZI,Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies,10.5582/bst.2020.01047,,,,,2020,"Gao, Jianjun; Tian, Zhenxue; Yang, Xu",BioScience Trends,2767584895,#1246,
,CZI,COVID-19: Real-time dissemination of scientific information to fight a public health emergency of international concern,10.5582/bst.2020.01056,,32092748,,"Rapidly sharing scientific information is an effective way to reduce public panic about COVID-19, and doing so is the key to providing real-time guidance to epidemiologists working to contain the outbreak, clinicians managing patients, and modelers helping to understand future developments and the possible effectiveness of various interventions. This issue has rapidly reviewed and published articles describing COVID-19, including the drug treatment options for SARS-CoV-2, its clinical characteristics, and therapies involving a combination of Chinese and Western medicine, the efficacy of chloroquine phosphate in the treatment of COVID-19 associated pneumonia according to clinical studies, and reflections on the system of reserve medical supplies for public health emergencies. As an academic journal, we will continue to quickly and transparently share data with frontline healthcare workers who need to know the epidemiological and clinical features of COVID-19.",2020,"Song, Peipei; Karako, Takashi",Biosci Trends,1559091631,#1766,
,CZI,Discovering drugs to treat coronavirus disease 2019 (COVID-19),10.5582/ddt.2020.01012,,,,"The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.",2020,"Dong, Liying; Hu, Shasha; Gao, Jianjun",Drug Discoveries & Therapeutics,2604381070,#5186,
,CZI,An outbreak of COVID ‐19 caused by a new coronavirus: what we know so far,10.5694/mja2.50530,,,,"An outbreak of a novel coronavirus, now formally named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and causing coronavirus disease 2019 (COVID‐19), emerged in the city of Wuhan in Hubei province in central China in December 2019. The first cases were noted as a cluster of patients with pneumonia who were all linked to a live animal market, and testing found the presence of a previously unknown coronavirus. Coronaviruses are a group of viruses that affect both animals and humans, and several (OC43, 229E, HKU1 and NL63) are a cause of the common cold.1, 2 However, two coronaviruses have previously caused significant outbreaks associated with more severe disease: the SARS coronavirus in 2002–2003 and the Middle East respiratory syndrome coronavirus that emerged in 2012.1, 2 Chinese authorities and researchers should be commended for their rapid sharing of viral sequences which enabled laboratories worldwide to develop diagnostic tests within weeks of discovery of the pathogen.3 An Australian laboratory subsequently isolated the virus from a clinical sample (the first to do so outside of China), and rapidly shared this virus with relevant global agencies, further aiding diagnostic, therapeutic and vaccine development efforts. Information on the new virus and its impact is being updated constantly. We know that SARS‐CoV‐2 can cause severe disease, although active surveillance of contacts is required to define the milder end of the disease spectrum and to estimate the true hospitalisation and case fatality ratio. The cases reported to date suggest that most are older adults; it is currently unclear whether comorbidities reflect the age group affected or whether they are risk factors for severe disease.4, 5 Early studies using data before the institution of public health interventions in China suggest that SARS‐CoV‐2 is as transmissible as SARS coronavirus and probably more transmissible than influenza viruses.6, 7 The timing of infectiousness relative to symptom onset is a particularly important parameter with implications for public health control. While reports suggest that asymptomatic infection and transmission may result from minimally symptomatic cases, the contribution of this to transmission is not yet known.8 Careful analysis of early data suggests that the mean incubation period is 6 days, with a range of up to 14 days.9 Reports of large outbreaks, particularly associated with hospitals and closed communities, raise the possibility of “superspreading” events, a feature of previous coronavirus outbreaks.10 The importance of infection control is also reinforced by a report that 41% of cases in Wuhan were acquired nosocomially (including 40 health care workers and 17 patients).4 As at 26 February 2020, there were 23 confirmed cases of COVID‐19 in Australia, across five jurisdictions. Although reported case numbers in China are slowing, large outbreaks on a cruise ship in Japan, and in South Korea, Iran and Italy are concerning and highlight our interconnected world. However, it is likely that this will change in the days or weeks ahead. Although absolute case numbers are small in Australia, the public health, political and societal ramifications have already been considerable, ranging from travel restrictions on non‐Australians coming from China, the use of offshore and remote quarantine facilities, and disturbing reports of racism against members of our Asian community (https://insightplus.mja.com.au/2020/5/coronavirus-no-place-for-racism-xenophobia/).",2020,"Cheng, Allen C.; Williamson, Deborah A.",Medical Journal of Australia,,#5128,
,CZI,"Reporting, Epidemic Growth, and Reproduction Numbers for the 2019 Novel Coronavirus (2019-nCoV) Epidemic",10.7326/M20-0358,,32023340,,,2020,"Tuite, Ashleigh R.; Fisman, David N.",Ann Intern Med,3004479334,#268,
,CZI,Disease control of 2019-novel coronavirus infection in hospital: West China urgent recommendation,10.7507/1672-2531.202001121,,,,"China is facing the serious situation of 2019-novel coronavirus (2019-nCoV) infection. The health care institutions have actively participated in the prevention, diagnosis, and treatment of the disease. Proper regulation of in-hospital policy may help control virus spreading. We developed seven key clinical questions about the prevention and control of 2019-novel coronavirus infection in a hospital, and provided recommendations based on the best available evidence and expert experience. We interpret the recommendations for better feasibility in Chinese hospital. We hope to provide evidence and reference for the domestic medical institutions to reasonably adjust the hospital workflow during 2019-nCoV infection period.",2020,"Li, S.; Huang, W.; Liao, X.; Li, D.; Du, L.; Song, J.; Zhou, Y.; Zhao, S.; Wang, Y.; Cao, X.; Wang, J.; Liu, J.; Zhu, S.; Li, L.; Hao, Q.; Zong, Z.; Sun, X.; Li, W.",Chinese Journal of Evidence-Based Medicine,3005477624,#3359,
,CZI,2019-novel coronavirus infection in a three-month-old baby,10.7759/cureus.4949,,,,,2020,"Zhang, Yuehua; Lin, Zhang; Xiao, Meifang; Wang, Jiachong; Wei, Yong; Lei, Zhixian; Zeng, Zhenqiong; Li, Ling; Li, Hongai; Xiang, Wei",Chinese Journal of Pediatrics,2951323607,#699,
,CZI,What we know so far: COVID-19 current clinical knowledge and research,10.7861/clinmed.2019-coron,,32139372,,"In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market. Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak. The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan. Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics. This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features.",2020,"Lake, M. A.","Clinical medicine (London, England)",2775275772,#4794,
,CZI,Development of Genetic Diagnostic Methods for Novel Coronavirus 2019 (nCoV-2019) in Japan,10.7883/yoken.JJID.2020.061,,,,"At the end of 2019, pneumonia caused by novel coronavirus 2019 (nCoV) emerged in Wuhan city, China. Many airline travelers moved between Wuhan and Japan at that time, suggesting that Japan is at high risk of invasion by the virus. Diagnostic systems for 2019-nCoV were developed with urgency. Two nested RT-PCR assays and two real-time RT-PCR assays were adapted to local Japanese conditions. As of 8 February 2020, the assays developed have successfully detected 25 positive cases of infection in Japan.",2020,"Shirato, Kazuya; Nao, Naganori; Katano, Harutaka; Takayama, Ikuyo; Saito, Shinji; Kato, Fumihiro; Katoh, Hiroshi; Sakata, Masafumi; Nakatsu, Yuichiro; Mori, Yoshio; Kageyama, Tsutomu; Matsuyama, Shutoku; Takeda, Makoto",Japanese Journal of Infectious Diseases,3003886061,#5227,
,CZI,Finding an Accurate Early Forecasting Model from Small Dataset: A Case of 2019-nCoV Novel Coronavirus Outbreak,10.9781/ijimai.2020.02.002,,,,"Epidemic is a rapid and wide spread of infectious disease threatening many lives and economy damages. It is important to fore-tell the epidemic lifetime so to decide on timely and remedic actions. These measures include closing borders, schools, suspending community services and commuters. Resuming such curfews depends on the momentum of the outbreak and its rate of decay. Being able to accurately forecast the fate of an epidemic is an extremely important but difficult task. Due to limited knowledge of the novel disease, the high uncertainty involved and the complex societal-political factors that influence the widespread of the new virus, any forecast is anything but reliable. Another factor is the insufficient amount of available data. Data samples are often scarce when an epidemic just started. With only few training samples on hand, finding a forecasting model which offers forecast at the best efforts is a big challenge in machine learning. In the past, three popular methods have been proposed, they include 1) augmenting the existing little data, 2) using a panel selection to pick the best forecasting model from several models, and 3) fine-tuning the parameters of an individual forecasting model for the highest possible accuracy. In this paper, a methodology that embraces these three virtues of data mining from a small dataset is proposed. An experiment that is based on the recent coronavirus outbreak originated from Wuhan is conducted by applying this methodology. It is shown that an optimized forecasting model that is constructed from a new algorithm, namely polynomial neural network with corrective feedback (PNN+cf) is able to make a forecast that has relatively the lowest prediction error. The results showcase that the newly proposed methodology and PNN+cf are useful in generating acceptable forecast upon the critical time of disease outbreak when the samples are far from abundant.",2020,"Fong, Simon James; Li, Gloria; Dey, Nilanjan; Gonzalez-Crespo, Rubén; Herrera-Viedma, Enrique",International Journal of Interactive Multimedia and Artificial Intelligence,3004754245,#3177,
,CZI,Coronavirus : rester proactif,,,32022502,,,2020,"Gardier, Stéphany; Petignat, Christiane",Rev Med Suisse,,#323,
,CZI,2019-nCoV : leçons d’incertitudes et de mondialisation,,,32049463,,,2020,"Matter, Michel",Rev Med Suisse,,#750,
,CZI,The possibility of using Lopinave/Litonawe (LPV/r) as treatment for novel coronavirus (2019-nCov)pneumonia: a quick systematic review based on earlier coronavirus clinical studies,,,,,"<p><b>Objective</b>To explore the possibility of using Lopinave/Litonawe (LPV/r) as treatment for novel coronavirus 2019-nCov pneumonia by systematically review earlier coronavirus studies.</p><p><b>Methods </b>Systematically retrieve relevant clinical studies from Chinese and English databases such as CNKI,VIP,Wangfang Data,CBM,PubMed, Web of Science,EMBASE. In addition, information from Chinese biomedical journals, WHO, US CDC, Chinese CDC websites and the references from published relevant articles were retrieved. The inclusion period is from January 2003 to January 24, 2020. The criteria for inclusion are:(1) studies that aim to compare LPV/r and placebo/standard for SARS, MERS; (2) studies that include at least one clinical outcome; (3) studies with diagnosis criteria meeting WHO requirement on SARS or MERS; (4)data from multiple reports but originated from one study, where we extract information from all reports; (5)guidelines, includes: national or academic guidelines/experts ‘consensus. The exclude criteria are: 1) only have abstracts but no full information; 2) in vitro studies. Two reviewers independently review articles and extract data on study design, patients, diagnosis criteria, regimen, and clinical outcomes (mortality, morbidity, quality of life, steroids dosage, chest image and adverse responses). </p><p><b>Results</b>Two hundred and thirty potential article were found by screening, and narrow down to forty-four articles for evaluation and fnally four studies were included. The results of included studies indicate the early use of LPV/r regimen can reduce the mortality of SARS and MERS, and reduce steroids dosing. </p><p><b>Conclusions</b>ILPV/r can be used as a component of experimental regimen for treat 2019-nCoV pneumonia. It strongly suggests that initiating real world studies to explore the true clinical effects of LPV/r on 2019-nCoV patients.</p>",2020,"Jiang, Hua; Deng, Hongfei; Wang, YU; Liu, Zhan; Sun, Mingwei; Zhou, Ping; Xia, Qi; Lu, Charles Damien; Zeng, Jun",Chinese Journal of Emergency Medicine,,#1050,
,CZI,Novo Coronavírus (2019-nCoV): nota técnica,,,,,"A Secretaria da Saúde do Estado do Ceará (SESA), através da Célula de Imunização (CEMUN) e o Centro de Informações Estratégicas em Vigilância em Saúde (CIEVS), da Coordenadoria de Vigilância Epidemiológica e Prevenção em Saúde (COVEP), vem por meio desta ALERTAR para a ocorrência de casos do Novo Coronavírus (2019-nCoV) no mundo.Essa nota deve ser divulgada amplamente entre profissionais de saúde de estabelecimentos públicos e privados",2020,"Ceará. Secretaria de, Saúde",,,#1860,
,CZI,Infecciones por Coronavirus. Diagnóstico y Tratamiento,,,,,"Boletín bibliográfico Bibliomed Suplemento ofrece en su edición especial de enero de 2020, una actualización sobre "Infecciones por Coronavirus. Diagnóstico yTratamiento"",2020,"Cuba. Centro Nacional de Información de Ciencias Médicas. Biblioteca Médica, Nacional",Boletín bibliográfico de la Biblioteca Médica Nacional,,#1852,
,CZI,"Initial Public Health Response and Interim Clinical Guidance for the 2019 Novel Coronavirus Outbreak — United States, December 31, 2019–February 4, 2020 | MMWR",,,,,"CDC, multiple other federal agencies, state and local health departments, and other partners are implementing aggressive measures to slow transmission of 2019-nCoV in the United States, be ready if widespread transmission occurs, and work on medical countermeasures.",2020,@CDCgov,,,#348,
,CZI,COVID-19 Update – March 2020 | Global Health | JN Learning | JAMA Ed Hub [Video recording],,,,,"Coronavirus testing, mortality, vaccine development, containment vs mitigation, and more. Anthony S. Fauci, MD discusses the latest developments in the global spread of COVID-19 and the SARS-CoV-2 virus with JAMA Editor Howard Bauchner, MD. - What's the difference between COVID-19 and SARS-CoV-2? (01:15) - What's the status and accuracy of diagnostic testing in the US? (01:58) - What's the case-fatality rate for the virus? (05:31) - Scientific advances and vaccine development (25:06) - Are current clinical trials providing a picture of treatments? (13:41) - Risk communication: how do we present information so there's faith that it's accurate? (15:24) - Risk groups (children, the elderly, pregnant women) (16:26) - Containment vs mitigation vs quarantine vs isolation (19:10) - Protecting the elderly and nursing home resident (23:52) - Public health prospects in Latin America, Africa (26:35) - Will coronavirus wane in warmer months like influenza? (27:52) - Why is anxiety so high about this disease?- Does the US have capacity to care for COVID19 infection? (31:03) - What is your daily schedule like? (32:23)",2020,JAMA,,,#4744,
,CZI,"Circular externa No 0000005 de 2020: Directrices para la detección temprana, el control y la atención ante la posible introducción del nuevo coronavirus (2019-nCoV) y la implementación de los planes de preparación y respuesta ante este riesgo",,,,,"El Ministerio de Salud y Protección Social y el Instituto Nacional de Salud, en ejercicio de las facultades señaladas en los Decretos 4107 y 4109, ambos de 2.011, y en el marco del Reglamento Sanitario Internacional -RSI-2005, y ante la situación epidemiológica por el nuevo coronavirus (2019-nCoV), declarada como emergencia en salud pública de importancia internacional (ESPII) por la Organización Mundial de la Salud (OMS) el día 30 de enero del año en curso: imparten instrucciones sobre las acciones que los destinatarios de esta circular deben observar para la vigilancia activa, preparación y toma de medidas de contención para una eventual introducción del virus en el territorio nacional. The Ministry of Health and Social Protection and the National Institute of Health, in exercise of the powers indicated in Decrees 4107 and 4109, both of 2,011, and within the framework of the International Health Regulations -RSI-2005, and before the epidemiological situation by the new coronavirus (2019-nCoV), declared as an emergency in public health of international importance (ESPII) by the World Health Organization (WHO) on January 30 of this year: they give instructions on the actions that the recipients of This circular must observe for the active surveillance, preparation and taking of containment measures for an eventual introduction of the virus into the national territory.",2020,"Ministerio de Salud y protección, Social; Instituto Nacional de, Salud",,,#1797,
,CZI,Orientaciones a puntos de entrada al país para el tamizaje de viajeros que vienen de zonas con circulación del nuevo coronavirus (2019-nCoV),,,,,El presente documento define lineamientos para realizar el tamizaje de los viajeros internacionales que ingresan al país; inicia con la identificación de viajeros por personal de Migración Colombia que son derivados para entrevista; continúa con la clasificación de potencial caso sospechoso y finaliza con la activación del plan de contingencias y emergencias del aeropuerto. This document defines guidelines for screening international travelers entering the country; it begins with the identification of travelers by Colombian Immigration personnel who are referred to interview; it continues with the classification of potential suspect case and ends with the activation of the airport's contingency and emergency plan.,2020,"Colombia. Ministerio de Salud y Protección, Social",,,#784,
,CZI,Protocolo para la atención de personas con sospechas o infección confirmada por Coronavirus (2019-nCoN),,,,,"El protocolo contiene definiciones de casos sospechosos, manejo de pacientes con sospecha de infección por Coronavirus, tratamiento específicos anti-Novel CoV e investigación clínica y las consideraciones especiales para pacientes embarazadas.",2020,"Perú. Ministerio de, Salud; Dirección General de Intervenciones Estratégicas en Salud, Pública",,,#1786,
,CZI,Protocolo para la atención de personas con sospechas o infección confirmada por Coronavirus (2019-nCoN)[Spanish],,,,,"El protocolo contiene definiciones de casos sospechosos, manejo de pacientes con sospecha de infección por Coronavirus, tratamiento específicos anti-Novel CoV e investigación clínica y las consideraciones especiales para pacientes embarazadas.",2020,"Perú. Ministerio de, Salud; Dirección General de Intervenciones Estratégicas en Salud, Pública",,,#1035,
,CZI,Protocolo de Manejo Clínico para o Novo Coronavírus (2019-nCoV),,,,,"Em 22 de janeiro de 2020, foi ativado o Centro de Operações de Emergências em Saúde Pública para o novo Coronavírus (COE nCoV), estratégia prevista no Plano Nacional de Resposta às Emergências em Saúde Pública do Ministério da Saúde. O novo Coronavírus (2019-nCoV) é um vírus identificado como a causa de um surto de doença respiratória detectado pela primeira vez em Wuhan, China. Desde 2005, o Sistema Único de Saúde (SUS) está aprimorando suas capacidades de responder às emergências por síndromes respiratórias, dispondo de planos, protocolos, procedimentos e guias para identificação, monitoramento e resposta às emergências em saúde pública...",2020,"Brasil. Ministerio da Saúde. Secretaria de Atenção Especializada à Saúde. Departamento de Atenção Hospitalar, Domiciliar e de Urgência Coordenação-Geral de Urgência Força Nacional do Sistema Único de Saúde",,,#1864,
,CZI,Directrices de Laboratorio para la detección y diagnóstico de la Infección con el Nuevo Coronavirus 2019 (2019-nCoV),,,,,"En las directrices de laboratorio para la detección y diagnóstico de la infección con el nuevo coronovirus 2019 la Organización Panamericana de la Salud/Organización Mundial de la Salud (OPS/OMS) recomienda a los Estados Miembros garantizar su identificación oportuna, el envío de las muestras a laboratorios nacionales y de referencia y la implementación del protocolo de detección molecular para 2019-nCoV, según la capacidad del laboratorio.",2020,"Organización Panamericana de la, Salud",,,#749,
,CZI,"Update: Public Health Response to the Coronavirus Disease 2019 Outbreak — United States, February 24, 2020 | MMWR",,,,,"Fourteen cases have been diagnosed in the United States, in addition to 39 cases among repatriated persons from high-risk settings, for a current total of 53 cases within the United States. U.S. government agencies and public health partners are implementing aggressive measures to slow and try to contain transmission of COVID-19 in the United States.",2020,"Jernigan, Daniel B.",,,#1981,
,CZI,"Persons Evaluated for 2019 Novel Coronavirus — United States, January 2020 | MMWR",,,,,"Health care providers should remain vigilant about possible 2019 novel coronavirus (2019-nCoV) exposures not only among returning travelers from China, but also among those in close contact with persons with 2019-nCoV in the United States.",2020,"Kristina L. Bajema, MD1, 2; Alexandra M. Oster, MD3; Olivia L. McGovern, PhD1, 2; Stephen Lindstrom, PhD4; Mark R. Stenger, MA5; Tara C. Anderson, DVM, PhD6; Cheryl Isenhour, DVM2; Kevin R. Clarke, MD7; Mary E. Evans, MD8; Victoria T. Chu, MD1, 4; Holly M. Biggs, MD4; Hannah L. Kirking, MD4; Susan I. Gerber, MD4; Aron J. Hall, DVM4; Alicia M. Fry, MD9; Sara E. Oliver, MD2; Team, -nCoV Persons Under Investigation",MMWR,,#632,
,CZI,"The 2019 Novel Coronavirus Outbreak – Update From NIAID’s Anthony Fauci, MD",,,,,"In February 2020 the nature of the 2019-nCoV outbreak is still slowly coming into focus but it appears to be acting more like bad pandemic influenza (efficient spread, overall lower mortality) than like SARS (less efficient spread, overall higher mortality). Dr. Anthony Fauci of the US National Institute of Allergy and Infectious Diseases (NIAID) discusses the latest developments with JAMA Editor Howard Bauchner.Coronavirus Resource Center",2020,,,,#554,
,CZI,"Acciones en promoción de la salud, prevención y atención de la Infección Respiratoria Aguda - IRA- ante alerta internacional por Nuevo Coronavirus 2019-nCoV",,,,,"La Organización Mundial de Salud (OMS) informó la ocurrencia de casos de Infección Respiratoria Aguda Grave (IRAG) causada por un nuevo coronavirus (2019-nCoV) en Wuhan (China), desde la última semana de diciembre de 2019. Los primeros casos se presentaron en personas que estuvieron en un mercado de pescado y animales silvestres de Wuhan, no obstante, se han confirmado casos en personas que estuvieron en esta y otras zonas de China y en 20 países de 4 continentes. El 30 enero del 2020 la OMS declara emergencia de salud pública de importancia internacional (ESPII). The World Health Organization (WHO) reported the occurrence of cases of Acute Respiratory Infection Severe (IRAG) caused by a new coronavirus (2019-nCoV) in Wuhan, China, since last week December 2019. The first cases involved people who were in a fish and wildlife in Wuhan, however, cases have been confirmed in people who were in this and other areas of China and in 20 countries on 4 continents. On 30 January 2020 the WHO declares a public health emergency of international concern (ESPII).",2020,"Colombia. Ministerio de Salud y Protección, Social",,,#785,
,CZI,"In the pipeline Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine. All content is Derek’s own, and he does not in any way speak for his employer",,,,,"Let’s take inventory on the therapies that are being developed for the coronavirus epidemic. Here is a very thorough list of at Biocentury, and I should note that (like Stat and several other organizations) they’re making all their Covid-19 content free to all readers during this crisis. I’d like to zoom in today on the potential small-molecule therapies, since some of these have the most immediate prospects for use in the real world. The ones at the front of the line are repurposed drugs that are already approved for human use, for a lot of obvious reasons. The Biocentury list doesn’t cover these, but here’s an article at Nature Biotechnology that goes into detail. Clinical trials are a huge time sink – they sort of have to be, in most cases, if they’re going to be any good – and if you’ve already done all that stuff it’s a huge leg up, even if the drug itself is not exactly a perfect fit for the disease. So what do we have? The compound that is most advanced is probably remdesivir from Gilead, at right. This has been in development for a few years as an RNA virus therapy – it was originally developed for Ebola, and has been tried out against a whole list of single-strand RNA viruses. That includes the related coronaviruses SARS and MERS, so Covid-19 was an obvious fit. The compound is a prodrug – that phosphoramide gets cleaved off completely, leaving the active 5-OH compound GS-44-1524. It mechanism of action is to get incorporated into viral RNA, since it’s taken up by RNA polymerase and it largely seems to evade proofreading. This causes RNA termination trouble later on, since that alpha-nitrile C-nucleoside is not exactly what the virus is expecting in its genome at that point, and thus viral replication is inhibited.",2020,"Derek, Lowe; Doerffler, Edward; Clarke, Michael O.; Chun, Kwon; Zhang, Lijun; Neville, Sean; Carra, Ernest; Lew, Willard; Ross, Bruce; Wang, Queenie; Wolfe, Lydia; Jordan, Robert; Soloveva, Veronica; Knox, John; Perry, Jason; Perron, Michel; Stray, Kirsten M.; Barauskas, Ona; Feng, Joy Y.; Xu, Yili; Lee, Gary; Rheingold, Arnold L.; Ray, Adrian S.; Bannister, Roy; Strickley, Robert; Swaminathan, Swami; Lee, William A.; Bavari, Sina; Cihlar, Tomas; Lo, Michael K.; Warren, Travis K.; Mackman, Richard L.",,,#5177,
,CZI,‘This beast is moving very fast.’ Will the new coronavirus be contained—or go pandemic? | Science | AAAS,,,,,"Modelers are trying to forecast how the virus will move, but they need better data",2020,@NewsfromScience,,,#347,
,CZI,“The disruption is enormous.” Coronavirus epidemic snarls science worldwide | Science | AAAS,,,,,"Normal daily life has come to a virtual standstill in large parts of China as a result of the epidemic of COVID-19—and so has science. Universities across the country remain closed; access to labs is restricted, projects have been mothballed, field work interrupted, and travel severely curtailed. But scientists elsewhere in the world are noticing an impact as well, as collaborations with China are on pause and scientific meetings for the next five months have been canceled or postponed. The damage to science pales compared to the human suffering; the total number of cases has risen to 71,429, the World Health Organization (WHO) reported today, almost 99% of them in China, and there have been 1775 deaths. Still, for individual researchers the losses can be serious—and stressful. “Basically, everything has completely stopped,” says John Speakman, who runs an animal behavior lab at the Chinese Academy of Sciences (CAS) in Beijing that has effectively been shut since the Lunar New Year on 25 January. “The disruption is enormous. The stress on the staff is really high.” But Speakman says he understands why the Chinese government took the measures. “It’s annoying, but I completely support what they have done,” he says.",2020,"Service, Robert F.",,,#1115,
,CZI,Guidance on strengthening the management processes of children′s fever in outpatient department during the novel coronavirus pneumonia epidemic period (First Edition),,,,,"Novel Coronavirus Pneumonia (NCP) is a class B infectious disease, which is prevented and controlled according to class A infectious diseases. Recently, children′s NCP cases have gradually increased, and children′s fever outpatient department has become the first strategic pass to stop the epidemic. Strengthening the management of the fever diagnosis process is very important for early detection of suspected children, early isolation, early treatment and prevention of cross-infection. This article proposes prevention and control strategies for fever diagnosis, optimizes processes, prevents cross-infection, health protection and disinfection of medical staff, based on the relevant diagnosis, treatment, prevention and control programs of the National Health and Health Commission and on the diagnosis and treatment experience of experts in various provinces and cities. The present guidance summarizes current strategies on pre-diagnosis; triage, diagnosis, treatment, and prevention of 2019-nCoV infection in common fever, suspected and confirmed children, which provide practical suggestions on strengthening the management processes of children′s fever in outpatient department during the novel coronavirus pneumonia epidemic period.",2020,"ZHANG, Guocheng; CHENG, Xiaoning; DING, Hui; SHI, Zhaoling; LI, Ruying; FU, Zhou; CHEN, Qiang; ZHAO, Dongchi; JIN, Runming; NIE, Guoming; LU, Jirong; LIU, Changshan; ZHAO, Deyu; PAN, Jiahua; FENG, Zhichun; SHI, Yuan; XIA, Zhengkun; ZHENG, Chengzhong; JIANG, Jinjin; WANG, Junxia; ZHENG, Yuejie; SHANG, Yunxiao; XIANG, Wei; XU, Baoping; SHEN, Kunling; WANG, Tianyou; YANG, Yonghong; LU, Quan",Chinese Journal of Applied Clinical Pediatrics,,#2066,
,CZI,Manual de bioseguridad para prestadores de servicios de salud que brinden atención en salud ante la eventual introducción del nuevo coronavirus (nCoV-2019) a Colombia,,,,,"Objetivo: Orientar a los Prestadores de Servicios de Salud del país sobre las normas de bioseguridad que se requieren implementar, frente a casos sospechosos o confirmados del nuevo coronavirus (nCoV-2019), con el fin de disminuir el riesgo de transmisión del virus de humano a humano durante la atención. En salud, evitando la presentación de casos en trabajadores de la salud, demás personal que labore en el ámbito de atención, y en otros pacientes que se encuentren en las instalaciones del prestador de servicios de salud. Objective: To provide guidance to the country's health service providers on the biosecurity standards that need to be implemented for suspected or confirmed cases of the new coronavirus (nCoV-2019), in order to reduce the risk of human-to-human transmission of the virus during care. In health, avoiding the presentation of cases in health workers, other personnel working in the care setting, and other patients in the health service provider's facilities.",2020,"Ministerio de Salud y Protección, Social",,,#937,
,CZI,‘A completely new culture of doing research.’ Coronavirus outbreak changes how scientists communicate | Science | AAAS,,,,,"On 22 January, Dave O’Connor and Tom Friedrich invited several dozen colleagues around the United States to join a new workspace on the instant messaging platform Slack. The scientists, both at the Wisconsin National Primate Research Center, had seen news about a new disease emerging in China and realized researchers would need a primate model if they were going to answer some important questions about its biology. “We put out a call to a bunch of investigators and basically said: ‘Hey, let’s talk,’” O’Connor says. The idea is to coordinate research and make sure results are comparable, Friedrich adds. (They named the Slack workspace the Wu-han Clan, a play on the hip-hop group Wu-Tang Clan.) The Wu-han Clan is just one example of how the COVID-19 outbreak is transforming how scientists communicate about fast-moving health crises. A torrent of data is being released daily by preprint servers that didn’t even exist a decade ago, then dissected on platforms such as Slack and Twitter, and in the media, before formal peer review begins. Journal staffers are working overtime to get manuscripts reviewed, edited, and published at record speeds. The venerable New England Journal of Medicine (NEJM) posted one COVID-19 paper within 48 hours of submission. Viral genomes posted on a platform named GISAID, more than 200 so far, are analyzed instantaneously by a phalanx of evolutionary biologists who share their phylogenetic trees in preprints and on social media.",2020,"Kupferschmidt, Kai",Science Magazine,,#2221,
,CZI,Novo Coronavírus: fluxo de atendimento na aps para o novo coronavírus (2019-NCOV),,,,,"priorizar o atendimento de casos suspeitos de novo Coronavírus, medidas de controle e registrar o atendimento no sistema de informação da Atenção Primária (SISAB)",2020,"Brasil. Ministerio da, Saude",,,#1865,
,CZI,"Lineamientos para la detección y manejo de casos por los prestadores de servicios de salud, frente a la eventual introducción del nuevo coronavirus (2019-ncov) a Colombia",,,,,"Propósito: orientar a los Prestadores de Servicios de Salud del país para la detección, atención y manejo de casos sospechosos de infección causada por el nuevo Coronavirus (nCoV-2019) para disminuir el riesgo de transmisión del virus de humano a humano. Purpose: to guide the country's health care providers in the detection, care, and management of suspected cases of infection caused by the new Coronavirus (nCoV-2019) in order to reduce the risk of human-to-human transmission of the virus.",2020,"Ministerio de Salud y Protección, Social",,,#936,
,CZI,Scientists question China’s decision not to report symptom-free coronavirus cases,,,,,"Researchers say that excluding these people could conceal the epidemic’s true extent, but others say the practice makes sense. Researchers are concerned that China’s official reports on the number of coronavirus infections have not been including people who have tested positive for the virus but who have no symptoms. They fear the practice is masking the epidemic’s true scale. But public health experts say China is right to prioritize tracking sick patients who are spreading the disease.",2020,Nature,Nature,,#1371,
,CZI,The race to unravel the United States’ biggest coronavirus outbreak,,,,,"Rohit Shankar left the virology laboratory at 2 a.m. on Wednesday, and was back at the lab bench by 7 a.m. the same day. “It’s okay,” he says, “I had a doughnut and a coffee.” Shankar, a medical scientist, and his colleagues at the University of Washington in Seattle are poised to exponentially drive up the number of confirmed cases of the coronavirus disease COVID-19 around the city, in western Washington state. That’s because this week, they began analysing a mountain of nose and throat swabs collected from hospitals in the region. Already, the researchers are seeing clear signs that the virus has infected vastly more people than have been formally detected. Scientists fear coronavirus spread in countries least able to contain it Washington state has become the United States’ ground zero for COVID-19, which has now spread to more than 90 countries worldwide in what seems to be a new and dangerous phase of the outbreak. Washington has declared a state emergency, and ten people there have died from the disease. But the number of confirmed cases in Washington — 70 — is still an underestimate resulting from a lack of testing, researchers agree. A genomic analysis posted online on 29 February suggested that hundreds of people in western Washington might already be infected. Academic scientists have mostly been prevented from measuring the extent of the US outbreak because of federal rules restricting the number of labs qualified to run diagnostic tests. But that is changing now, and helps account for why the state's caseload jumped from 10 to 70 this week. Dozens of virologists and genomicists have now kicked into high gear in Seattle, dropping or adapting projects to devote resources to the outbreak. Researchers are working around the clock to find out how many people have the disease in the area. Others are analysing genomes to reveal how the virus is transmitted or developing new therapies. The scientists are racing to help Washington avoid the fate of Hubei province in China, where more than 2,900 people have died of COVID-19 so far. The coronavirus emerged in the province’s city Wuhan in December, and the initial response from officials was slow. “We are past the point of containment,” says Helen Chu, an infectious-disease specialist at the University of Washington School of Medicine (UW Medicine) in Seattle. “So now we need to keep the people who are vulnerable from getting sick.”",2020,"Maxmen, Amy",,,#4900,
,CZI,Scientist decries ‘completely chaotic’ conditions on cruise ship Japan quarantined after viral outbreak | Science | AAAS,,,,,"SHARE Share on facebook 80 Share on twitter Share on linkedin Share on reddit 3 Share on mailto A port security officer at the Diamond Princess in Yokohama, Japan’s port. Passengers who tested negative for the coronavirus began to leave the cruise ship today. EUGENE HOSHIKO/AP Scientist decries ‘completely chaotic’ conditions on cruise ship Japan quarantined after viral outbreak By Dennis NormileFeb. 19, 2020 , 2:45 PM A Japanese infectious disease specialist has harshly criticized the way Japan’s government has handled the COVID-19 crisis aboard a luxury cruise ship docked in Yokohama. Conditions on board the Diamond Princess were “violating all infection control principles” and “completely chaotic,” the scientist, Kentaro Iwata of Kobe University, said in a YouTube video posted on Tuesday evening. His claims are inflaming an already intense debate over Japan’s handling of the crisis. Scientists have also faulted the slow release of epidemiological data about the ship that could help control efforts elsewhere.",2020,"Normile, Dennis",,,#1279,
,CZI,The United States badly bungled coronavirus testing—but things may soon improve | Science | AAAS,,,,,"Speed is critical in the response to COVID-19. So why has the United States been so slow in its attempt to develop reliable diagnostic tests and use them widely? The World Health Organization (WHO) has shipped testing kits to 57 countries. China had five commercial tests on the market 1 month ago and can now do up to 1.6 million tests a week; South Korea has tested 65,000 people so far. The U. S. Centers for Disease Control and Prevention (CDC), in contrast, has done only 459 tests since the epidemic began. The rollout of a CDC-designed test kit to state and local labs has become a fiasco because it contained a faulty reagent. Labs around the country eager to test more suspected cases—and test them faster—have been unable to do so. No commercial or state labs have the approval to use their own tests. In what is already an infamous snafu, CDC initially refused a request to test a patient in Northern California who turned out to be the first probable COVID19 case without known links to an infected person.",2020,"Cohen, Jon",Science Magazine,,#2779,
,CZI,Daily briefing: World’s biggest physics meeting cancelled over coronavirus fears,,,,,The March Meeting of the APS was cancelled just 36 hours before it was scheduled to begin today. Plus: the best repositories for life-sciences imaging data and how to find early-career grants and fellowships.,2020,"Graham, Flora",Nature,,#3172,
,CZI,How Coronaviruses Cause Infection—from Colds to Deadly Pneumonia,,,,,The novel coronavirus outbreak raises questions about how such pathogens evolve and what makes infections mild or severe,2020,"Makin, Simon",,,#294,
,CZI,Advices on the prevention and control of nosocomial infection of novel coronavirus within children’s hospitals,,,,,"The pneumonia caused by the novel coronavirus (2019-nCoV), which began in December 2019, has become the most serious public health problem, threatening people's health and life. This threat is posing a severe challenge on the diagnosis and treatment of 2019-nCoV infection, the prevention and control of hospital cross infection of medical staff. It is suggested that in addition to strengthening the organization and leadership of the abovementioned work, establishing and improving the prevention and control mechanism deserve greater attention. Furthermore, special attention should be given to the safety of the medical staff, strengthening their infection monitoring and outbreak management. Medical staff in different work areas and positions should be placed under careful protection, cleaning and disinfection measures. The protection during specimen collection, transportation and medical waste management should also be prioritized. This paper also put forward management suggestions for the outpatient department, isolation ward and other key departments. These measures are proposed to provide a guidance for the prevention and control of 2019-nCoV nosocomial infection in the pediatric outpatient and ward.",2020,"XU, Hongzhen; CHEN, Shuohui; FU, Junfen; SHU, Qiang; CHEN, Zhimin; SUN, Wei; WANG, Dan; ZHU, Haihong; ZHOU, Hongqin; HUANG, Guolan; FU, Zangzang; ZHAO, Hangyan; WANG, Bin; WU, Xiaoqing; LIANG, Yuqin; HUANG, Yufen; GU, Meihong; WANG, Wei",Chinese Journal of Hospital Administration,,#2106,
,CZI,‘This beast is moving very fast.’ Will the new coronavirus be contained—or go pandemic?,,,,,"The silver lining of the epidemic is that scientists have collected and shared information at record speed. “Every day that goes by we know more and every day that goes by we can do better modeling,” Vespignani says. “Unfortunately, this beast is moving very fast.”",2020,"Cohen, Kai Kupferschmidt; Jon",Science,,#332,
,CZI,Novo Coronavírus: atendimento a pessoas com suspeita de infecção pelo novo coronavírus (2019-nCoV) na Atenção Primária à Saúde,,,,,,2020,"Brasil. Ministerio da, Saude",,,#1866,
,CZI,Novo coronavirus (2019 nCov) Medidas de prevenção e controle de infecção a serem adotadas na ssistência à saúde,,,,,,2020,"São Paulo Secretaria da, Saúde",,,#922,
,CZI,The prevention and control of a new coronavirus infection in department of stomatology,,,32057210,,"During a short period of time, the outbreak of pneumonia caused by a novel coronavirus, named Novel Coronavirus Pneumonia (NCP), was first reported in China, spreading to 24 countries and regions rapidly. The number of confirmed cases and deaths continued to rise. World Health Organization (WHO) announced that the outbreaks of the novel coronavirus have constituted a Public Health Emergency of International Concern. Efficient infection control can prevent the virus from further spreading, which makes the epidemic situation under control. Due to the specialty of oral healthcare settings, the risk of cross infection is severe among patients and oral healthcare practitioners. It's more urgent to implement strict and efficient infection control protocols. This paper, based on existing guidelines and published researches pertinent to dental infection-control principles and practices, mainly discusses epidemiological characteristics of NCP and the features of nosocomial infection in oral healthcare settings, and furthermore provides recommendations on patient's evaluation, and infection control protocols in department of stomatology under current circumstance..",2020,"LI, Zhi yong; MENG, Liu yan",Chinese Journal of Stomatology,2377782053,#1228,
,CZI,COVID-19: another infectious disease emerging at the animal-human interface,,,32078596,,,2020,"Murdoch, David R.; French, Nigel P.",N Z Med J,2185518228,#1541,
,CZI,Dynamic changes of chest CT imaging in patients with corona virus disease-19 (COVID-19),,,32096366,,"OBJECTIVE: To analyze the dynamic changes of chest CT images of patients with corona virus disease-19 (COVID-19). METHODS: Fifty-two cases of COVID-19 were admitted in the First Affiliated Hospital of Zhejiang University School of Medicine. The consecutive chest CT scans were followed up for all patients with an average of 4 scans performed per patient during the hospitalization. The shortest interval between each scan was 2 days and the longest was 7 days. The shape, number and distribution of lung shadows, as well as the characteristics of the lesions on the CT images were reviewed. RESULTS: The obvious shadows infiltrating the lungs were shown on CT images in 50 cases, for other 2 cases there was no abnormal changes in the lungs during the first CT examination. Ground-glass opacities (GGO) were found in 48 cases (92.3%), and 19 cases (36.5%) had patchy consolidation and sub-consolidation, which were accompanied with air bronchi sign in 17 cases (32.7%). Forty one cases (78.8%) showed a thickened leaflet interval, 4 cases (7.6%) had a small number of fibrous stripes. During hospitalization, GGO lesions in COVID-19 patients gradually became rare, the fibrous strip shadows increased and it became the most common imaging manifestation. The lesions rapidly progressed in 39 cases (75.0%) within 6-9 days after admission. On days 10-14 of admission, the lesions distinctly resolved in 40 cases (76.9%). CONCLUSIONS: The chest CT images of patients with COVID-19 have certain characteristics with dynamic changes, which are of value for monitoring disease progress and clinical treatment.",2020,"Wang, Jincheng; Liu, Jinpeng; Wang, Yuanyuan; Liu, Wei; Chen, Xiaoqun; Sun, Chao; Shen, Xiaoyong; Wang, Qidong; Wu, Yaping; Liang, Wenjie; Ruan, Lingxiang",Zhejiang Da Xue Xue Bao Yi Xue Ban,2349102525,#1922,
,CZI,Novel coronavirus COVID-19: an overview for emergency clinicians,,,32105049,,"Prior to the global outbreak of SARS-CoV in 2003, HCoV-229E and HCoV-OC43 were the only coronaviruses known to infect humans. Following the SARS outbreak, 5 additional coronaviruses have been discovered in humans, most recently the novel coronavirus COVID-19, believed to have originated in Wuhan, Hubei Province, China. SARS-CoV and MERSCoV are particularly pathogenic in humans and are associated with high mortality. In this review, the epidemiology, pathophysiology, and management of the recently discovered COVID-19 are reviewed, with a focus on best practices and the public health implications.",2020,"Giwa, A.; Desai, A.",Emergency medicine practice,3005413696,#2815,
,CZI,"Coronavirus 9-nCoV: recomendaciones para aeropuertos, puertos y pasos fronterizos",,,,,"Ante la situación mundial, en relación a 2019-nCoV, que implica la posibilidad de ingreso a nuestro país de personas infectadas, se generaron las recomendaciones necesarias para la detección temprana y control de pacientes con posibilidad de presentar una enfermedad respiratoria aguda al ingreso a nuestro país. La principal estrategia es la detección temprana y control de los casos posibles. En los Aeropuertos, Puertos y Pasos Fronterizos se está realizando difusión masiva de información para viajeros en relación a 2019-nCoV, con el objetivo de generar conciencia acerca de la importancia de las medidas de prevención, los síntomas ante los cuales se debe solicitar atención y el teléfono de consulta ministerial sanitaria (0800-222-1002 - opción 1)",2020,"Argentina. Ministerio de, Salud",,1604377110,#801,
,CZI,Novel Coronavirus Disease 2019 (COVID-19): An Emerging Infectious Disease in the 21st Century,,,,,"Background: At the beginning of the New Year 2020, China alerted the world health organization (WHO) to a cluster of unusual pneumonia cases in Wuhan. After extensive speculation, eventually a new species of coronavirus introduced as the causative pathogen of the disease. Coronavirus disease 2019 (COVID-19) is a name for the disease, and the virus that causes it is known SARS-CoV-2. The very rapid spread of the COVID-19 in China and in many other countries has caused fear among people across the world. The novel coronavirus outbreak declared a Public Health Emergency of International Concern on 30 January 2020. Materials and Methods: Several databases such as PubMed, Scopus, Google scholar, and BioRxiv were searched for publications reporting on the novel coronavirus up to 29 February 2020. Literature searches were performed using keywords including “Coronavirus 2019”, “2019-nCoV”, “COVID-19”, and “SARS-CoV-2”. Moreover, websites such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) were searched to retrieve updated data and statistics regarding the novel coronavirus. We extracted data on the epidemiology, pathogenesis, virology, clinical manifestations, transmission routes, diagnosis, treatment, and prevention measures. Results: From the 1416 articles identified in the initial search, 53 were remained after title and abstract screening. After full-text review, 37 articles were eligible to include in our study. Incubation period for COVID-19 is between 2-10 days, according to the World Health Organization (WHO). The case fatality rate in patients infected with SARC-CoV-2 is 4.3%, and the results indicate that the mortality is higher in elderly individuals and patients with chronic conditions including patients with coronary artery disease, diabetes, chronic pulmonary disease, and hypertension. The mortality rate in healthy subjects is less than 1%. Conclusion: The outbreak caused by the novel coronavirus is larger than the previous human coronaviruses, showing that the SARS-CoV-2 is an extremely contagious virus. However, the mortality rate of COVID-19 is lower than that of other coronaviruses diseases such as SARS or MERS and other viruses like HIV and Ebola. Currently, due to the lack of an effective treatment and vaccine, the best way to deal with the COVID-19 disease is to prevent transmission and spread of the virus and to execute personal protective measures.",2020,"Keshavarz, Ahmad Tavakoli; Katayon, Vahdat; Mohsen",Iranian South Medical Journal,621380834,#4536,
,CZI,Coronavirus just caused the American Physical Society to cancel its biggest meeting of the year | Science | AAAS,,,,,"Citing the growing threat of the coronavirus, the American Physical Society (APS), the 55,000 member professional society for physicists and researchers in associated fields, cancelled its largest meeting of the year just 34 hours before it was supposed to begin. APS’s March Meeting was to be held this week at the Colorado Convention Center in Denver, and the society anticipated more than 10,000 people from all over the world would attend. However, late yesterday, APS issued a statement abruptly calling off the meeting. “The decision to cancel was based on the latest scientific data being reported, and the fact that a large number of attendees at this meeting are coming from outside the U.S.,” including countries where the virus is circulating and for which the U.S. Centers for Disease Control and Prevention have advised people to avoid non-essential travel, the APS statement says. “[T]his decision was made out of deep concern for the health and well-being of our registrants, staff, vendors, and the Denver community.”",2020,"Cho, Adrian",Science Magazine,2595674569,#2772,
,CZI,Mensajero de la Salud: nuevo coronavirus 2019-nCoV,,,,,Declaratoria de Emergencia en Salud Pública de importancia Internacional por el nuevo coronavirus 2019-nCoV,2020,"Mexico. Secretaria de la, Salud",,3003591461,#1803,
,CZI,The management of biosafety risk in clinical laboratory of hospital during the outbreak of 2019 Novel Coronavirus disease,,,,,"During the outbreak of coronavirus disease-19 (COVID-19), the clinical laboratories of hospitals designated for the disease treatment is undertaking a lot of clinical testing work of infectious specimens. How to manage the biosafety risk is a major problem that the clinical laboratory and the nosocomial infection control department are facing. This article introduces the hierarchical prevention and control biosafety measures in the clinical laboratory from the perspective of the laboratory, with a view to provide reasonable and feasible methods for the clinical laboratories of hospitals at various levels during the outbreak.",2020,"XIAO, Yuling; LU, Xiaojun; KANG, Mei; LI, Dongdong; JIANG, Hong; CHEN, Jie; YING, Binwu; XIE, Yi",Chinese Journal of Laboratory Medicine,2194450012,#2110,
,CZI,Lineamiento estandarizado para la Vigilancia Epidemiologica y por laboratorio de enfermedad por 2019-NCoV,,,,,"Este documento describe la situación epidemiológica de la enfermedad por 2019-nCoV, los lineamientos para la detección y seguimiento de los casos, así como los aspectos de la toma, manejo y envío adecuado de las muestras y el control analítico disponible para la confirmación de los casos.",2020,"Mexico. Secretaria de Salud. Subsecretaria de Prevencion y Promoción de la Salud. Dirección General de, Epidemiologia",,2241123449,#1802,
,CZI,Singapore claims first use of antibody test to track coronavirus infections | Science | AAAS,,,,,"In what appears to be a first, disease trackers in Singapore have used an experimental antibody test for COVID-19 to confirm that a suspected patient was infected with the coronavirus. The patient was one of two people who together formed a missing link between two clusters of cases that each occurred in a Singaporean church. Researchers around the world are racing to develop antibody tests, also called serological tests, that can confirm whether someone was infected even after their immune system has cleared the virus that causes COVID-19. The group that developed the test, at Duke-NUS Medical School in Singapore, is among the front-runners, although its assay has to be validated before it is taken into production and deployed widely.",2020,"Normile, Dennis",Science Magazine,2855667717,#2584,
,CZI,"The network investigation on knowledge, attitude and practice about Novel coronavirus pneumonia of the residents in Anhui Province",,,,,"Objective To analyze the current situation of the knowledge, attitudes and practice about Novelcoronavirus pneumonia (NCP) of the residents in Anhui Province. Methods Anonymous network sampling survey was carried out with an electronic questionnaire that designed by the questionnaire star, and a total of 4016 subjects from Anhui province were investigated. The content of the survey includes that the basic information of subjects,the residents' knowledge, attitudes and practice about NCP, as well as their satisfaction with the prevention and control measures adopted by the government and health authorities and the suggestions on future prevention. The questionnaire doesn't involve any privacy information, and all questions were mandatory to ensure the response rate. Results The M(P 25 , P 75 )age the 4 016 subjects was 21 (19, 24) years old, and the ranging from 7 to 80 years old. The number of males was 1 431(35.6%). Social networking tools such as WeChat and QQ were the main sources of epidemic information for residents (97.8%, 3 929 respondents). Residents had higher awareness rate of cough (99.5%, n= 3 997) and fever(96.0%, n= 3 857) symptoms, the transmission by droplets (99.5%, n= 3 995), aerosol transmission (81.1%, n= 3 258), and contact transmission (92.3%, n= 3 708), but lower awareness of symptoms os muscle pain or fatigue (62.7%, n= 2 518). 92.6% of the subjects ( n= 3 720) think that the outbreak was scary. In terms of psychological behavior scores, the results showed that female (9.38±4.81), the urban (9.37±5.02) and the medical workers (10.79±5.19) had a poorer mental health than the male (8.45±5.00), the rural (8.71±4.75) and the non-medical workers (the students: 8.85±4.83; public institude workers: 9.02±5.08; others: 8.97±5.39) ( P <0.05). 71.9% of the residents ( n= 2 887)were satisfied with the local epidemic control measures. The residents took various of the measures to prevent and control the epidemic. The ratio of residents that could achieve'no gathering and less going out','wear masks when going out'and'do not go to crowded and closed places'was up to 97.4% ( n= 3 913), 93.6% ( n= 3758) and 91.5% ( n= 3 673) respectively. Conclusion The residents in Anhui province have a good KAP about NCP, yet it is necessary to strengthen the community publicity, the mental health maintenance of residents and students' health education.",2020,"CHEN, Yan",Chinese Journal of Preventive Medicine,2363410972,#2333,
,CZI,Investigation on demands for antenatal care services among 2 002 pregnant women during the epidemic of coronavirus disease 2019 in Shanghai,,,,,"Objective To identify problems and demands for antenatal care (ANC) among pregnant women in different trimesters of pregnancy in Shanghai for optimizing ANC service during the epidemic of coronavirus disease 2019 (COVID-19). Methods Organized by Maternal and Child Health Care institute in the 16 districts of Shanghai, a cross sectional study was conducted among pregnant women who came to pregnancy registration in the community health centers or attended ANC in maternity hospitals from February 7 to February 12, 2020. Consented participating women completed a semi-structured online questionnaire voluntarily. Data was analyzed using frequency and scoring, chi-square test. Results A total of 2 002 valid questionnaires were collected from 183 community health centers and 67 midwifery hospitals. About 94.6% of the pregnant women worried about being infected during the COVID-19 epidemic, and 14.7% demanded for psychological consultation. Appointment ANC services were requested by 87.7% of the participants for avoiding presenting themselves in people-density places. Compared with other pregnancy trimesters, pregnant women in the second trimester were more willing to reduce the frequency of ANC (48.1% VS. 39.5% VS. 35.2%, P <0.01). Compared with multiparas, primiparas were more willing to have online consultation and guidance (63.8% VS. 49.2%, P <0.01). Regarding the needs for health knowledge on COVID-19, personal protection against 2019-nCoV was the most concerned for pregnant women, and 71.0% of them preferred to obtain knowledge through health applications, official Weibo and WeChat. Conclusions Pregnant women in Shanghai critically concern about the risk of 2019-nCoV infections, and highly demand knowledge and measures on prevention and protection from COVID-19. They ask for having time-lapse appointments for ANC and online access to health information and services. Maternal and Child Care institutes should understand the demands of pregnant women, optimize the means of ANC service, and provide tailored and accessible health education and service for the safety of mother and child.",2020,"DU, Li; GU, Yibin; CUI, Mengqing; LI, Wenxian; WANG, Jie; ZHU, Liping; XU, Biao",Chinese Journal of Obstetrics and Gynecology,1891209719,#2305,
,CZI,Analysis of early chest high resolution CT images of novel coronavirus pneumonia,,,,,"Objective To investigate the first chest HRCT imaging manifestations infected with novel coronavirus pneumonia (NCP). Method A retrospective analysis of the first chest HRCT images of 106 patients with NCP clinically diagnosed in our hospital from January 3 to 25, 2020. Lesion distribution, morphology and surrounding involvement were analyzed. Result Lesions were found in the first lung HRCT of 106 patients, with unilateral lung distribution in 11 cases (10.4%), bilateral lung distribution in 95 cases (89.6%), and peripheral distribution of lung in 65 cases (61.3%). 41 cases (38.7%) were distributed at the same time; 8 cases (7.5%) were 1 lesion, 5 cases (4.7%) were 2 lesions, 93 cases (87.8%) were multiple lesions, and 12 cases were nodular lesions (11.3%). 94 cases of ground-glass lesions (88.7%), 7 cases of cord-like lesions (6.6%), 15 cases (14.2%) of coexisting lesions of two or more forms; 10 cases (9.4%) involving one lung lobe There were 96 cases (90.6%) involving two or more lung lobes; 24 cases (22.6%) with enlarged mediastinal lymph nodes (19 cases over 60 years old, accounting for 79.2%); 3 cases with pleural effusion (2.8 %), 1 case had pericardial effusion (0.9%), and 2 cases had pleural involvement / thickening (1.9%). Patients over 60 years of age mostly present with multiple lesions, multiple morphology, peripheral and central distribution of lungs, involving multiple lung lobes, and enlarged mediastinal lymph nodes. Conclusions Lung lesions of NCP patients can be detected for the first time by chest HRCT, which is the preferred imaging method. Thoracic HRCT scans play an important role in the early diagnosis of new coronavirus (NCP). .",2020,"LIU, Haifeng; ZHANG, Dongyou; YANG, Yi; LONG, Bin; YIN, Long; ZHAO, Ming; PENG, Yong",Chinese Journal of Radiology,2418493795,#2187,
,CZI,Novo Coronavirus (nCoV),,,,,"Os Coronavírus (CoV) compõem uma grande família de vírus, conhecidos desde meados da década de 1960. Podem causar desde um resfriado comum até síndromes respiratórias graves, como a síndrome respiratória aguda grave (SARS - Severe Acute Respiratory Syndrome) e a síndrome respiratória do Oriente Médio (MERS - Middle East Respiratory Syndrome). Os casos agora identificados estão relacionados a uma nova variante do Coronavírus, denominada 2019-nCoV, até então não identificada em humanos.",2020,"Rio de Janeiro . Secretaria de Estado de Saúde. Subsecretaria de Vigilância em, Saúde",Nota Técnica-SVS/SES-RJ,2518954822,#216,
,CZI,Difficulties and strategies of public hospitals in their participation in the prevention and control of novel coronavirus pneumonia,,,,,"Outbreak of the novel coronavirus pneumonia (NC) across the country has seriously threatened people's lives and health, endangering smooth operation of the national economy and social stability. An all-out campaign to save the NCP patients and reduce their mortality is not only one of the key tasks to fight against the epidemic, but also a major responsibility and mission of public hospitals. In view of the field practice of Wuhan Union Hospital in the epicenter, the authors Described the challenges faced by such hospitals in the prevention and control, summarized its experiences and proposed improvement measures, for reference of other public hospitals and relevant authorities.",2020,"XU, Dong; HU, Yu; DING, Ning; XIA, Jiahong; ZHANG, Yidan; WEI, Li; ZHANG, Ming; WAN, Jie",Chinese Journal of Hospital Administration,2348898337,#2108,
,CZI,Get Real,,,,,"Since this is going to be a post about the coronavirus, let’s start off with this PSA: wash your hands. ... OK, either tomorrow or Friday I hope to do a post on all the things that are going on in the biopharma industry for a possible coronavirus treatment. ... It was clearly related to the virus from the first case (reported on January 19 in the same county in Washington state), descended from it in a way that makes it almost certain that the coronavirus has been spreading undetected among that population for weeks.",2020,"Lowe, Derek",Science,2343731596,#3808,
,CZI,How Ophthalmologists Should Understand and Respond to the Current Epidemic of Novel Coronavirus Pneumonia (COVID-19),,,,,"The new coronavirus pneumonia that first appeared in Wuhan, China, in December 2019 has attracted great attention from both the Chinese government and the international community. The International Committee on Viral Classification named the virus 'Severe Acute Respiratory Syndrome Coronavirus 2' (SARS-CoV-2), and the WHO named the pneumonia it causes 'Coronavirus Disease 2019' (COVID-19). At present, the disease is centered in Wuhan City and is spreading rapidly to all parts of China, as well as twenty other countries. About 20% of the people infected during the SARS epidemic in 2003 were employees in hospital environments. COVID-19 has infected an even greater number of heath care workers. Therefore, ophthalmologists need to understand the disease and recognize the importance of taking preventive measures. Although ophthalmologists do not work on the front lines of the outbreak, due to their area of expertise, a variety of situations, such as infection consultations or ophthalmic emergency treatments, can lead to the exposure of ophthalmologists to high-risk environments. This risk will only increase as the number of infected patients continues to increase. When dealing with seemingly normal ophthalmic patients, the vigilance of ophthalmologists and associated staff tends to be significantly reduced. To better protect patients, families, and health care workers, it is strongly recommended that in addition to the standard precautions for the care of all patients, strict contact precautions and droplet precautions need to be taken by ophthalmologists. These measures include 1) wearing an efficient mask (an N95 mask); 2) always performing hand hygiene before and after examining a patient; (3) wearing sterile gloves when entering a patient’s room and touching a patient; (4) wearing a gown when contact is expected with items and environmental surfaces surrounding a patient or when the patient is incontinent or has diarrhea or a surgical or other invasive wound with oozing fluid; 5) cleaning and disinfecting ophthalmic equipment and correctly handling medical waste after examination to prevent transmission to patients who are subsequently examined; 6) wearing goggles and a disposable mask to cover the front and sides of the face before touching a patient, as the virus could spread through the ocular surface; 7) performing the relevant screening for novel coronavirus pneumonia for regular patients who have conjunctivitis and respiratory symptoms at the same time; 8) prohibiting the use of infected patients as potential donors for corneal transplants and temporarily adding donor SARS-CoV-2 screening to the medical standard of the eye bank during the outbreak; and 9) for the purposes of scientific research, diagnosis, and other special needs, packing, shipping, and transporting collected specimens according to the relevant dangerous biological goods regulations.",2020,"ZHIJIE, Li",Chinese Journal of Experimental Ophthalmology,3005943294,#2051,
,CZI,Experts proposal and frequently asked questions of rapid screening and prevention of novel coronavirus pneumonia in children,,,,,"The outbreak of novel coronavirus pneumonia (NCP) has become the most severe public health issue at the moment, threatening people′s lives. Pediatricians in Shanghai have recently launched a discussion on the focused questions of NCP, including the incidence situation, epidemiological features, essentials of early screening, treatment and nosocomial infection prevention of children′s novel coronavirus infection (2019-nCoV), and further put forward the experts proposal upon the patterns of disease occurrence, development, diagnosis and control, for the reference of frontline pediatricians.",2020,"ZHANG, Lei; CAO, Qing; WANG, Ying; LU, Quan; HONG, Jianguo; YIN, Yong; ZHANG, Xiaobo; ZHANG, Jianhua; LU, Min; DONG, Xiaoyan; LU, Yanming; ZHANG, Jing; ZHANG, Jian",Chinese Journal of Applied Clinical Pediatrics,2416639376,#2063,
,CZI,Surgical treatment strategy for digestive system malignancies during the outbreak of novel coronavirus pneumonia,,,,,"The outbreak of novel coronavirus pneumonia occurred in Wuhan, Hubei province of China, at the end of 2019, and spread rapidly across the country. After the outbreak of this disease, the overwhelming majority of cities have launched the 'first level response' and the regular diagnosis and treatment of cancer patients are greatly affected. The digestive systemic cancer is the most common malignancy. Most patients are diagnosed in the advanced stage with poor prognosis. The epidemic of novel coronavirus pneumonia poses new challenges to diagnosis and treatment of the patients with digestive system malignancies. Based on the fully understanding of the characteristics of digestive system tumors, we should change the treatment strategy and adopt more reasonable treatment strategy timely during the epidemic period to minimize the adverse effects of the epidemic of novel coronavirus pneumonia on the treatment.",2020,"MA, Fuhai; HU, Haitao; TIAN, Yantao",Chinese Journal of Oncology,2366820445,#2176,
,CZI,Novel coronavirus pneumonia in the primary general hospital of treatment based on traditional Chinese medicine syndrome differentiation and prevention,,,,,"To observe the curative effect of TCM syndrome differentiation and treatment for novel coronavirus pneumonia (novel coronavirus pneumonia, NCP) patients and the preventive effect for Chinese medical staff. Methods. A total of 62 NCP suspected patients admitted in 2020 were treated with TCM syndrome differentiation and treatment, as well as our hospital medical staff with No.1-4 hospital prescription. After taking traditional Chinese medicine, 16 out of 25 NCP suspected patients with phlegm heat stagnating lung syndrome were discharged to home for isolation observation, 4 patients hospitalized for observation, and 5 patients confirmed with NCP. For 15 patients with phlegm dampness accumulating lung syndrome, 7 patients were discharged to home for isolation observation, 3 patients were hospitalized for observation and 5 patients have been confirmed. For 18 patients with spleen stomach disharmony syndrome, 15 patients were discharged to home for isolation observation, 1 patient was hospitalized for observation and 2 patients have been confirmed. For 4 patients with Qi deficiency and dampness stagnation syndrome were discharged to home for isolation observation, 1 patient was hospitalized for observation, and two have been confirmed. The duration of taking traditional Chinese medicine was 1 to 20 days from admission to be discharged. The doctors and nurses who took the prescription of TCM for 12 to 15 days have been prevented from NCP infection. Conclusions. The clinical effect and the preventive effect of TCM syndrome differentiation and treatment for NCP have been proved to be satisfactory. TCM can go into the primary hospital for treatment and prevention on NCP.",2020,"Liao, Rongye; Yang, Jie; Cao, Zhi; Wang, Jun",International Journal of Traditional Chinese Medicine,2616653490,#1962,
,CZI,"A Novel Coronavirus Outbreak from Wuhan City in China, Rapid Need for Emergency Departments Preparedness and Response; a Letter to Editor",,,,,,2020,"Alavi-Moghaddam, Mostafa",Archives of Academic Emergency Medicine,3006236663,#3509,
,CZI,History is repeating itself: Probable zoonotic spillover as the cause of the 2019 novel coronavirus epidemic,,,,,,2020,"Rodriguez-Morales, A. J.; Bonilla-Aldana, D. K.; Balbin-Ramon, G. J.; Rabaan, A. A.; Sah, R.; Paniz-Mondolfi, A.; Pagliano, P.; Esposito, S.",Infezioni in Medicina,3005681200,#926,
,CZI,"Epidemiological and Clinical Characteristics of 99 Cases of 2019-Novel Coronavirus (2019-nCoV) Pneumonia in Wuhan, China",,,,,,,"Chen, Nanshan and Zhou, Min and Dong, Xuan and Qu, Jieming and Gong, Fengyun and Han, Yang and Qiu, Yang and Wang, Jingli and Liu, Ying and Wei, Yuan and Xia, Jia'an and Yu, Ting and Zhang, Xinxin and Zhang, Li,",,3004580727,#22,
03203ab50eb64271a9e825f94a1b1a6c46ea14b3,PMC,Recombination Every Day: Abundant Recombination in a Virus during a Single Multi-Cellular Host Infection,http://dx.doi.org/10.1371/journal.pbio.0030089,PMC1054884,15737066,CC BY,"Viral recombination can dramatically impact evolution and epidemiology. In viruses, the recombination rate depends on the frequency of genetic exchange between different viral genomes within an infected host cell and on the frequency at which such co-infections occur. While the recombination rate has been recently evaluated in experimentally co-infected cell cultures for several viruses, direct quantification at the most biologically significant level, that of a host infection, is still lacking. This study fills this gap using the cauliflower mosaic virus as a model. We distributed four neutral markers along the viral genome, and co-inoculated host plants with marker-containing and wild-type viruses. The frequency of recombinant genomes was evaluated 21 d post-inoculation. On average, over 50% of viral genomes recovered after a single host infection were recombinants, clearly indicating that recombination is very frequent in this virus. Estimates of the recombination rate show that all regions of the genome are equally affected by this process. Assuming that ten viral replication cycles occurred during our experiment—based on data on the timing of coat protein detection—the per base and replication cycle recombination rate was on the order of 2 × 10(−5) to 4 × 10(−5). This first determination of a virus recombination rate during a single multi-cellular host infection indicates that recombination is very frequent in the everyday life of this virus.",2005 Mar 1,"['Froissart, Remy', 'Roze, Denis', 'Uzest, Marilyne', 'Galibert, Lionel', 'Blanc, Stephane', 'Michalakis, Yannis']",PLoS Biol,,,True
98a3b0606a67d829816c1d934e2d1a7196985151,PMC,Prospective evaluation of an internet-linked handheld computer critical care knowledge access system,http://dx.doi.org/10.1186/cc2967,PMC1065064,15566586,CC BY,"INTRODUCTION: Critical care physicians may benefit from immediate access to medical reference material. We evaluated the feasibility and potential benefits of a handheld computer based knowledge access system linking a central academic intensive care unit (ICU) to multiple community-based ICUs. METHODS: Four community hospital ICUs with 17 physicians participated in this prospective interventional study. Following training in the use of an internet-linked, updateable handheld computer knowledge access system, the physicians used the handheld devices in their clinical environment for a 12-month intervention period. Feasibility of the system was evaluated by tracking use of the handheld computer and by conducting surveys and focus group discussions. Before and after the intervention period, participants underwent simulated patient care scenarios designed to evaluate the information sources they accessed, as well as the speed and quality of their decision making. Participants generated admission orders during each scenario, which were scored by blinded evaluators. RESULTS: Ten physicians (59%) used the system regularly, predominantly for nonmedical applications (median 32.8/month, interquartile range [IQR] 28.3–126.8), with medical software accessed less often (median 9/month, IQR 3.7–13.7). Eight out of 13 physicians (62%) who completed the final scenarios chose to use the handheld computer for information access. The median time to access information on the handheld handheld computer was 19 s (IQR 15–40 s). This group exhibited a significant improvement in admission order score as compared with those who used other resources (P = 0.018). Benefits and barriers to use of this technology were identified. CONCLUSION: An updateable handheld computer system is feasible as a means of point-of-care access to medical reference material and may improve clinical decision making. However, during the study, acceptance of the system was variable. Improved training and new technology may overcome some of the barriers we identified.",2004 Oct 14,"['Lapinsky, Stephen E', 'Wax, Randy', 'Showalter, Randy', 'Martinez-Motta, J Carlos', 'Hallett, David', 'Mehta, Sangeeta', 'Burry, Lisa', 'Stewart, Thomas E']",Crit Care,,,True
d617306cda56236d02117ae7a5fc5e7fcd015554,PMC,Subversion of Cellular Autophagosomal Machinery by RNA Viruses,http://dx.doi.org/10.1371/journal.pbio.0030156,PMC1084330,15884975,CC BY,"Infection of human cells with poliovirus induces the proliferation of double-membraned cytoplasmic vesicles whose surfaces are used as the sites of viral RNA replication and whose origin is unknown. Here, we show that several hallmarks of cellular autophagosomes can be identified in poliovirus-induced vesicles, including colocalization of LAMP1 and LC3, the human homolog of Saccharomyces cerevisiae Atg8p, and staining with the fluorophore monodansylcadaverine followed by fixation. Colocalization of LC3 and LAMP1 was observed early in the poliovirus replicative cycle, in cells infected with rhinoviruses 2 and 14, and in cells that express poliovirus proteins 2BC and 3A, known to be sufficient to induce double-membraned vesicles. Stimulation of autophagy increased poliovirus yield, and inhibition of the autophagosomal pathway by 3-methyladenine or by RNA interference against mRNAs that encode two different proteins known to be required for autophagy decreased poliovirus yield. We propose that, for poliovirus and rhinovirus, components of the cellular machinery of autophagosome formation are subverted to promote viral replication. Although autophagy can serve in the innate immune response to microorganisms, our findings are inconsistent with a role for the induced autophagosome-like structures in clearance of poliovirus. Instead, we argue that these double-membraned structures provide membranous supports for viral RNA replication complexes, possibly enabling the nonlytic release of cytoplasmic contents, including progeny virions, from infected cells.",2005 May 26,"['Jackson, William T', 'Giddings, Thomas H', 'Taylor, Matthew P', 'Mulinyawe, Sara', 'Rabinovitch, Marlene', 'Kopito, Ron R', 'Kirkegaard, Karla']",PLoS Biol,,,True
d619c3ceec4db4f3f350c3d5fb3842bd83f04a80,PMC,The immediate effects of the severe acute respiratory syndrome (SARS) epidemic on childbirth in Taiwan,http://dx.doi.org/10.1186/1471-2458-5-30,PMC1084353,15804368,CC BY,"BACKGROUND: When an emerging infectious disease like severe acute respiratory syndrome (SARS) strikes suddenly, many wonder the public's overwhelming fears of SARS may deterred patients from seeking routine care from hospitals and/or interrupt patient's continuity of care. In this study, we sought to estimate the influence of pregnant women's fears of severe acute respiratory syndrome (SARS) on their choice of provider, mode of childbirth, and length of stay (LOS) for the delivery during and after the SARS epidemic in Taiwan. METHODS: The National Health Insurance data from January 01, 2002 to December 31, 2003 were used. A population-based descriptive analysis was conducted to assess the changes in volume, market share, cesarean rate, and average LOS for each of the 4 provider levels, before, during and after the SARS epidemic. RESULTS: Compared to the pre-SARS period, medical centers and regional hospitals dropped 5.2% and 4.1% in market share for childbirth services during the peak SARS period, while district hospitals and clinics increased 2.1% and 7.1%, respectively. For changes in cesarean rates, only a significantly larger increase was observed in medical centers (2.2%) during the peak SARS period. In terms of LOS, significant reductions in average LOS were observed in all hospital levels except for clinics. Average LOS was shortened by 0.21 days in medical centers (5.6%), 0.21 days in regional hospitals (5.8%), and 0.13 days in district hospitals (3.8%). CONCLUSION: The large amount of patients shifting from the maternity wards of more advanced hospitals to those of less advanced hospitals, coupled with the substantial reduction in their length of maternity stay due to their fears of SARS could also lead to serious concerns for quality of care, especially regarding a patient's accessibility to quality providers and continuity of care.",2005 Apr 4,"['Lee, Cheng-Hua', 'Huang, Nicole', 'Chang, Hong-Jen', 'Hsu, Yea-Jen', 'Wang, Mei-Chu', 'Chou, Yiing-Jenq']",BMC Public Health,,,True
d0c6b0c2d387baae89eb2898969913218b3bedff,PMC,Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies,http://dx.doi.org/10.1186/1743-422X-2-35,PMC1087510,15833113,CC BY,"In the aftermath of the SARS epidemic, there has been significant progress in understanding the molecular and cell biology of SARS-CoV. Some of the milestones are the availability of viral genome sequence, identification of the viral receptor, development of an infectious cDNA clone, and the identification of viral antigens that elicit neutralizing antibodies. However, there is still a large gap in our understanding of how SARS-CoV interacts with the host cell and the rapidly changing viral genome adds another variable to this equation. Now the SARS-CoV story has entered a new phase, a search for preventive strategies and a cure for the disease. This review highlights the progress made in identifying molecular aspects of SARS-CoV biology that is relevant in developing disease prevention strategies. Authors conclude that development of successful SARS-CoV vaccines and antivirals depends on the progress we make in these areas in the immediate future.",2005 Apr 15,"['Stark, Caren J', 'Atreya, CD']",Virol J,,,True
e6184d2db86268ba31e49b03a5aab475d5ce5ca6,PMC,Individual sequences in large sets of gene sequences may be distinguished efficiently by combinations of shared sub-sequences,http://dx.doi.org/10.1186/1471-2105-6-90,PMC1090557,15817134,CC BY,"BACKGROUND: Most current DNA diagnostic tests for identifying organisms use specific oligonucleotide probes that are complementary in sequence to, and hence only hybridise with the DNA of one target species. By contrast, in traditional taxonomy, specimens are usually identified by 'dichotomous keys' that use combinations of characters shared by different members of the target set. Using one specific character for each target is the least efficient strategy for identification. Using combinations of shared bisectionally-distributed characters is much more efficient, and this strategy is most efficient when they separate the targets in a progressively binary way. RESULTS: We have developed a practical method for finding minimal sets of sub-sequences that identify individual sequences, and could be targeted by combinations of probes, so that the efficient strategy of traditional taxonomic identification could be used in DNA diagnosis. The sizes of minimal sub-sequence sets depended mostly on sequence diversity and sub-sequence length and interactions between these parameters. We found that 201 distinct cytochrome oxidase subunit-1 (CO1) genes from moths (Lepidoptera) were distinguished using only 15 sub-sequences 20 nucleotides long, whereas only 8–10 sub-sequences 6–10 nucleotides long were required to distinguish the CO1 genes of 92 species from the 9 largest orders of insects. CONCLUSION: The presence/absence of sub-sequences in a set of gene sequences can be used like the questions in a traditional dichotomous taxonomic key; hybridisation probes complementary to such sub-sequences should provide a very efficient means for identifying individual species, subtypes or genotypes. Sequence diversity and sub-sequence length are the major factors that determine the numbers of distinguishing sub-sequences in any set of sequences.",2005 Apr 8,"['Gibbs, Mark J', 'Armstrong, John S', 'Gibbs, Adrian J']",BMC Bioinformatics,,,True
c6008b68c8b16e3a6a48a2cb892bac5c9353df86,PMC,Absence of association between angiotensin converting enzyme polymorphism and development of adult respiratory distress syndrome in patients with severe acute respiratory syndrome: a case control study,http://dx.doi.org/10.1186/1471-2334-5-26,PMC1090578,15819995,CC BY,"BACKGROUND: It has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele) of the angiotensin converting enzyme (ACE) gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS) in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D) polymorphism and the progression to ARDS or requirement of intensive care in SARS patients. METHOD: One hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis. RESULTS: There is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care. CONCLUSION: The ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection.",2005 Apr 9,"['Chan, KC Allen', 'Tang, Nelson LS', 'Hui, David SC', 'Chung, Grace TY', 'Wu, Alan KL', 'Chim, Stephen SC', 'Chiu, Rossa WK', 'Lee, Nelson', 'Choi, KW', 'Sung, YM', 'Chan, Paul KS', 'Tong, YK', 'Lai, ST', 'Yu, WC', 'Tsang, Owen', 'Lo, YM Dennis']",BMC Infect Dis,,,True
6f07f87e8ef78f0416556e69c88247e588f9192c,PMC,A Three-Stemmed mRNA Pseudoknot in the SARS Coronavirus Frameshift Signal,http://dx.doi.org/10.1371/journal.pbio.0030172,PMC1110908,15884978,CC BY,"A wide range of RNA viruses use programmed −1 ribosomal frameshifting for the production of viral fusion proteins. Inspection of the overlap regions between ORF1a and ORF1b of the SARS-CoV genome revealed that, similar to all coronaviruses, a programmed −1 ribosomal frameshift could be used by the virus to produce a fusion protein. Computational analyses of the frameshift signal predicted the presence of an mRNA pseudoknot containing three double-stranded RNA stem structures rather than two. Phylogenetic analyses showed the conservation of potential three-stemmed pseudoknots in the frameshift signals of all other coronaviruses in the GenBank database. Though the presence of the three-stemmed structure is supported by nuclease mapping and two-dimensional nuclear magnetic resonance studies, our findings suggest that interactions between the stem structures may result in local distortions in the A-form RNA. These distortions are particularly evident in the vicinity of predicted A-bulges in stems 2 and 3. In vitro and in vivo frameshifting assays showed that the SARS-CoV frameshift signal is functionally similar to other viral frameshift signals: it promotes efficient frameshifting in all of the standard assay systems, and it is sensitive to a drug and a genetic mutation that are known to affect frameshifting efficiency of a yeast virus. Mutagenesis studies reveal that both the specific sequences and structures of stems 2 and 3 are important for efficient frameshifting. We have identified a new RNA structural motif that is capable of promoting efficient programmed ribosomal frameshifting. The high degree of conservation of three-stemmed mRNA pseudoknot structures among the coronaviruses suggests that this presents a novel target for antiviral therapeutics.",2005 Jun 17,"['Plant, Ewan P', 'Pérez-Alvarado, Gabriela C', 'Jacobs, Jonathan L', 'Mukhopadhyay, Bani', 'Hennig, Mirko', 'Dinman, Jonathan D']",PLoS Biol,,,True
99b74061d99f96f6842cf3efea27058d680ed188,PMC,New Frameshifting Pseudoknot Found in SARS Virus,http://dx.doi.org/10.1371/journal.pbio.0030199,PMC1110910,,CC BY,,2005 Jun 17,,PLoS Biol,,,False
9ffde004c991e9cf3c63e9143946a64ffaa9ee2a,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,True
02b715cc786b21f3e45f79afe877f1c02e9bfd08,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
cdcdd72d94ba5194a20b73cd5332a76f2105df94,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
201de588b3a7dbcf1319dd201fd9ee806f1557d0,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
7178530e60694f264910bd591cc70a707d498bfa,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
8e6d79c06c141e0f13bb4ff2a007ba37b992829e,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
52885ace333b00bb8b096a70aa7f33383f456275,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
01d8f392a96f0b16e1a92bd00b001f82a2507018,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
e875c30d3311bba4f2fc9534c477c61c8d33db84,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
6fc5b537c91bd586409a0a74bde7eb19071467f4,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
fadbf9aa0290ab261722dffc3fb1d6fd486ce0a7,PMC,The Microbial Rosetta Stone Database: A compilation of global and emerging infectious microorganisms and bioterrorist threat agents,http://dx.doi.org/10.1186/1471-2180-5-19,PMC1127111,15850481,CC BY,"BACKGROUND: Thousands of different microorganisms affect the health, safety, and economic stability of populations. Many different medical and governmental organizations have created lists of the pathogenic microorganisms relevant to their missions; however, the nomenclature for biological agents on these lists and pathogens described in the literature is inexact. This ambiguity can be a significant block to effective communication among the diverse communities that must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a database known as the Microbial Rosetta Stone. The database relates microorganism names, taxonomic classifications, diseases, specific detection and treatment protocols, and relevant literature. The database structure facilitates linkage to public genomic databases. This paper focuses on the information in the database for pathogens that impact global public health, emerging infectious organisms, and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is available at . The database provides public access to up-to-date taxonomic classifications of organisms that cause human diseases, improves the consistency of nomenclature in disease reporting, and provides useful links between different public genomic and public health databases.",2005 Apr 25,"['Ecker, David J', 'Sampath, Rangarajan', 'Willett, Paul', 'Wyatt, Jacqueline R', 'Samant, Vivek', 'Massire, Christian', 'Hall, Thomas A', 'Hari, Kumar', 'McNeil, John A', 'Büchen-Osmond, Cornelia', 'Budowle, Bruce']",BMC Microbiol,,,False
c6c8b82bc5a800425b075540eff41b0af719f80f,PMC,HIV Epidemiology in Africa: Weak Variables and Tendentiousness Generate Wobbly Conclusions,http://dx.doi.org/10.1371/journal.pmed.0020137,PMC1140948,15916469,CC BY,,2005 May 31,"['Brody, Stuart', 'Potterat, John J']",PLoS Med,,,True
914c8d326beaccabd37199a9903b27fa7f9b0586,PMC,Pseudoknots: RNA Structures with Diverse Functions,http://dx.doi.org/10.1371/journal.pbio.0030213,PMC1149493,15941360,CC BY,"Just as proteins form distinct structural motifs, certain structures are commonly adopted by RNA molecules. Amongst the most prevalent is the RNA pseudoknot.",2005 Jun 14,"['Staple, David W', 'Butcher, Samuel E']",PLoS Biol,,,True
198ed53d956a2707716d175cc6516bb720f52d82,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,True
3c4e7b941e30be5bcd8c5222305bb53b5374f70c,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
c74cbed3524e1dd5d93d9db9d71c9f91ba8561e0,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
9c86de3d1107dd2c0fb8d9bb03fff120c41d6559,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
283fd3dad298787130f03473882a3dbf22420dc4,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
ce545fcd547a3bf435499dd84b5c87332a5c5879,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
5baa1fa52d730151424cc2a70242c7937016b815,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
c163182040644bbb1350c3d3acacacc431fb07aa,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
93f5284236b5257175bfff402f8b8ea90e0a79c0,PMC,Integration of the Gene Ontology into an object-oriented architecture,http://dx.doi.org/10.1186/1471-2105-6-113,PMC1156866,15885145,CC BY,"BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, ""transforming growth factor-beta (TGF-beta) receptor complex assembly"" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.",2005 May 10,"['Shegogue, Daniel', 'Zheng, W Jim']",BMC Bioinformatics,,,False
68b905ee32b8aad54ae9006fc7aab007c63e9895,PMC,Software for optimization of SNP and PCR-RFLP genotyping to discriminate many genomes with the fewest assays,http://dx.doi.org/10.1186/1471-2164-6-73,PMC1156889,15904493,CC BY,"BACKGROUND: Microbial forensics is important in tracking the source of a pathogen, whether the disease is a naturally occurring outbreak or part of a criminal investigation. RESULTS: A method and SPR Opt (SNP and PCR-RFLP Optimization) software to perform a comprehensive, whole-genome analysis to forensically discriminate multiple sequences is presented. Tools for the optimization of forensic typing using Single Nucleotide Polymorphism (SNP) and PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) analyses across multiple isolate sequences of a species are described. The PCR-RFLP analysis includes prediction and selection of optimal primers and restriction enzymes to enable maximum isolate discrimination based on sequence information. SPR Opt calculates all SNP or PCR-RFLP variations present in the sequences, groups them into haplotypes according to their co-segregation across those sequences, and performs combinatoric analyses to determine which sets of haplotypes provide maximal discrimination among all the input sequences. Those set combinations requiring that membership in the fewest haplotypes be queried (i.e. the fewest assays be performed) are found. These analyses highlight variable regions based on existing sequence data. These markers may be heterogeneous among unsequenced isolates as well, and thus may be useful for characterizing the relationships among unsequenced as well as sequenced isolates. The predictions are multi-locus. Analyses of mumps and SARS viruses are summarized. Phylogenetic trees created based on SNPs, PCR-RFLPs, and full genomes are compared for SARS virus, illustrating that purported phylogenies based only on SNP or PCR-RFLP variations do not match those based on multiple sequence alignment of the full genomes. CONCLUSION: This is the first software to optimize the selection of forensic markers to maximize information gained from the fewest assays, accepting whole or partial genome sequence data as input. As more sequence data becomes available for multiple strains and isolates of a species, automated, computational approaches such as those described here will be essential to make sense of large amounts of information, and to guide and optimize efforts in the laboratory. The software and source code for SPR Opt is publicly available and free for non-profit use at .",2005 May 16,"['Gardner, Shea N', 'Wagner, Mark C']",BMC Genomics,,,True
77aae7c898acfb4ff723de2af7928a38b169878a,PMC,CXCR2 is critical for dsRNA-induced lung injury: relevance to viral lung infection,http://dx.doi.org/10.1186/1476-9255-2-4,PMC1156932,15921526,CC BY,"BACKGROUND: Respiratory viral infections are characterized by the infiltration of leukocytes, including activated neutrophils into the lung that can lead to sustained lung injury and potentially contribute to chronic lung disease. Specific mechanisms recruiting neutrophils to the lung during virus-induced lung inflammation and injury have not been fully elucidated. Since CXCL1 and CXCL2/3, acting through CXCR2, are potent neutrophil chemoattractants, we investigated their role in dsRNA-induced lung injury, where dsRNA (Poly IC) is a well-described synthetic agent mimicking acute viral infection. METHODS: We used 6–8 week old female BALB/c mice to intratracheally inject either single-stranded (ssRNA) or double-stranded RNA (dsRNA) into the airways. The lungs were then harvested at designated timepoints to characterize the elicited chemokine response and resultant lung injury following dsRNA exposure as demonstrated qualititatively by histopathologic analysis, and quantitatively by FACS, protein, and mRNA analysis of BAL fluid and tissue samples. We then repeated the experiments by first pretreating mice with an anti-PMN or corresponding control antibody, and then subsequently pretreating a separate cohort of mice with an anti-CXCR2 or corresponding control antibody prior to dsRNA exposure. RESULTS: Intratracheal dsRNA led to significant increases in neutrophil infiltration and lung injury in BALB/c mice at 72 h following dsRNA, but not in response to ssRNA (Poly C; control) treatment. Expression of CXCR2 ligands and CXCR2 paralleled neutrophil recruitment to the lung. Neutrophil depletion studies significantly reduced neutrophil infiltration and lung injury in response to dsRNA when mice were pretreated with an anti-PMN monoclonal Ab. Furthermore, inhibition of CXCR2 ligands/CXCR2 interaction by pretreating dsRNA-exposed mice with an anti-CXCR2 neutralizing Ab also significantly attenuated neutrophil sequestration and lung injury. CONCLUSION: These findings demonstrate that CXC chemokine ligand/CXCR2 biological axis is critical during the pathogenesis of dsRNA-induced lung injury relevant to acute viral infections.",2005 May 28,"['Londhe, Vedang A', 'Belperio, John A', 'Keane, Michael P', 'Burdick, Marie D', 'Xue, Ying Ying', 'Strieter, Robert M']",J Inflamm (Lond),,,True
4ae8479c3cef7cc97b7edb7cb3e9f86ec51d140e,PMC,Persistence of lung inflammation and lung cytokines with high-resolution CT abnormalities during recovery from SARS,http://dx.doi.org/10.1186/1465-9921-6-42,PMC1156954,15888207,CC BY,"BACKGROUND: During the acute phase of severe acute respiratory syndrome (SARS), mononuclear cells infiltration, alveolar cell desquamation and hyaline membrane formation have been described, together with dysregulation of plasma cytokine levels. Persistent high-resolution computed tomography (HRCT) abnormalities occur in SARS patients up to 40 days after recovery. METHODS: To determine further the time course of recovery of lung inflammation, we investigated the HRCT and inflammatory profiles, and coronavirus persistence in bronchoalveolar lavage fluid (BALF) of 12 patients at recovery at 60 and 90 days. RESULTS: At 60 days, compared to normal controls, SARS patients had increased cellularity of BALF with increased alveolar macrophages (AM) and CD8 cells. HRCT scores were increased and correlated with T-cell numbers and their subpopulations, and inversely with CD4/CD8 ratio. TNF-α, IL-6, IL-8, RANTES and MCP-1 levels were increased. Viral particles in AM were detected by electron microscopy in 7 of 12 SARS patients with high HRCT score. On day 90, HRCT scores improved significantly in 10 of 12 patients, with normalization of BALF cell counts in 6 of 12 patients with repeat bronchoscopy. Pulse steroid therapy and prolonged fever were two independent factors associated with delayed resolution of pneumonitis, in this non-randomized, retrospective analysis. CONCLUSION: Resolution of pneumonitis is delayed in some patients during SARS recovery and may be associated with delayed clearance of coronavirus, Complete resolution may occur by 90 days or later.",2005 May 11,"['Wang, Chun-Hua', 'Liu, Chien-Ying', 'Wan, Yung-Liang', 'Chou, Chun-Liang', 'Huang, Kuo-Hsiung', 'Lin, Horng-Chyuan', 'Lin, Shu-Min', 'Lin, Tzou-Yien', 'Chung, Kian Fan', 'Kuo, Han-Pin']",Respir Res,,,True
eddc547cbba693715e4fd55e6a946e8ec7d96bc2,PMC,A Severe Acute Respiratory Syndrome extranet: supporting local communication and information dissemination,http://dx.doi.org/10.1186/1472-6947-5-17,PMC1166558,15967040,CC BY,"BACKGROUND: The objective of this study was to explore the use and perceptions of a local Severe Acute Respiratory Syndrome (SARS) Extranet and its potential to support future information and communication applications. The SARS Extranet was a single, managed electronic and limited access system to manage local, provincial and other SARS control information. METHODS: During July, 2003, a web-based and paper-based survey was conducted with 53 SARS Steering Committee members in Hamilton. It assessed the use and perceptions of the Extranet that had been built to support the committee during the SARS outbreak. Before distribution, the survey was user-tested based on a think-aloud protocol, and revisions were made. Quantitative and qualitative questions were asked related to frequency of use of the Extranet, perceived overall usefulness of the resource, rationale for use, potential barriers, strengths and limitations, and potential future uses of the Extranet. RESULTS: The response rate was 69.4% (n = 34). Of all respondents, 30 (88.2%) reported that they had visited the site, and rated it highly overall (mean = 4.0; 1 = low to 5 = high). However, the site was rated 3.4 compared with other communications strategies used during the outbreak. Almost half of all respondents (44.1%) visited the site at least once every few days. The two most common reasons the 30 respondents visited the Extranet were to access SARS Steering Committee minutes (63.3%) and to access Hamilton medical advisories (53.3%). The most commonly cited potential future uses for the Extranet were the sending of private emails to public health experts (63.3%), and surveillance (63.3%). No one encountered personal barriers in his or her use of the site, but several mentioned that time and duplication of email information were challenges. CONCLUSION: Despite higher rankings of various communication strategies during the SARS outbreak, such as email, meetings, teleconferences, and other web sites, users generally perceived a local Extranet as a useful support for the dissemination of local information during public health emergencies.",2005 Jun 20,"['Valaitis, Ruta K', 'Akhtar-Danesh, Noori', 'Kealey, Cathy M', 'Brunetti, Glenn M', 'Thomas, Helen']",BMC Med Inform Decis Mak,,,True
6d7084462a7462edc93ce2d350bf6dd08c232ef4,PMC,Peptide inhibitors of dengue virus and West Nile virus infectivity,http://dx.doi.org/10.1186/1743-422X-2-49,PMC1177995,15927084,CC BY,"Viral fusion proteins mediate cell entry by undergoing a series of conformational changes that result in virion-target cell membrane fusion. Class I viral fusion proteins, such as those encoded by influenza virus and human immunodeficiency virus (HIV), contain two prominent alpha helices. Peptides that mimic portions of these alpha helices inhibit structural rearrangements of the fusion proteins and prevent viral infection. The envelope glycoprotein (E) of flaviviruses, such as West Nile virus (WNV) and dengue virus (DENV), are class II viral fusion proteins comprised predominantly of beta sheets. We used a physio-chemical algorithm, the Wimley-White interfacial hydrophobicity scale (WWIHS) [1] in combination with known structural data to identify potential peptide inhibitors of WNV and DENV infectivity that target the viral E protein. Viral inhibition assays confirm that several of these peptides specifically interfere with target virus entry with 50% inhibitory concentration (IC50) in the 10 μM range. Inhibitory peptides similar in sequence to domains with a significant WWIHS scores, including domain II (IIb), and the stem domain, were detected. DN59, a peptide corresponding to the stem domain of DENV, inhibited infection by DENV (>99% inhibition of plaque formation at a concentrations of <25 μM) and cross-inhibition of WNV fusion/infectivity (>99% inhibition at <25 μM) was also demonstrated with DN59. However, a potent WNV inhibitory peptide, WN83, which corresponds to WNV E domain IIb, did not inhibit infectivity by DENV. Additional results suggest that these inhibitory peptides are noncytotoxic and act in a sequence specific manner. The inhibitory peptides identified here can serve as lead compounds for the development of peptide drugs for flavivirus infection.",2005 Jun 1,"['Hrobowski, Yancey M', 'Garry, Robert F', 'Michael, Scott F']",Virol J,,,True
04603867552ffafcaeff68fe8bf7f190ebb08a78,PMC,Appropriate Models for the Management of Infectious Diseases,http://dx.doi.org/10.1371/journal.pmed.0020174,PMC1181873,16013892,CC BY,"BACKGROUND: Mathematical models have become invaluable management tools for epidemiologists, both shedding light on the mechanisms underlying observed dynamics as well as making quantitative predictions on the effectiveness of different control measures. Here, we explain how substantial biases are introduced by two important, yet largely ignored, assumptions at the core of the vast majority of such models. METHODS AND FINDINGS: First, we use analytical methods to show that (i) ignoring the latent period or (ii) making the common assumption of exponentially distributed latent and infectious periods (when including the latent period) always results in underestimating the basic reproductive ratio of an infection from outbreak data. We then proceed to illustrate these points by fitting epidemic models to data from an influenza outbreak. Finally, we document how such unrealistic a priori assumptions concerning model structure give rise to systematically overoptimistic predictions on the outcome of potential management options. CONCLUSION: This work aims to highlight that, when developing models for public health use, we need to pay careful attention to the intrinsic assumptions embedded within classical frameworks.",2005 Jul 26,"['Wearing, Helen J', 'Rohani, Pejman', 'Keeling, Matt J']",PLoS Med,,,True
dd74c8f2961dc716ec9d0c412206c88e0cb9b314,PMC,Information theory-based algorithm for in silico prediction of PCR products with whole genomic sequences as templates,http://dx.doi.org/10.1186/1471-2105-6-190,PMC1183192,16042814,CC BY,"BACKGROUND: A new algorithm for assessing similarity between primer and template has been developed based on the hypothesis that annealing of primer to template is an information transfer process. RESULTS: Primer sequence is converted to a vector of the full potential hydrogen numbers (3 for G or C, 2 for A or T), while template sequence is converted to a vector of the actual hydrogen bond numbers formed after primer annealing. The former is considered as source information and the latter destination information. An information coefficient is calculated as a measure for fidelity of this information transfer process and thus a measure of similarity between primer and potential annealing site on template. CONCLUSION: Successful prediction of PCR products from whole genomic sequences with a computer program based on the algorithm demonstrated the potential of this new algorithm in areas like in silico PCR and gene finding.",2005 Jul 26,"['Cao, Youfang', 'Wang, Lianjie', 'Xu, Kexue', 'Kou, Chunhai', 'Zhang, Yulei', 'Wei, Guifang', 'He, Junjian', 'Wang, Yunfang', 'Zhao, Liping']",BMC Bioinformatics,,,True
a2fedab38bf51ed90c37c61d4f84838c56e5f18a,PMC,Genetic lesions within the 3a gene of SARS-CoV,http://dx.doi.org/10.1186/1743-422X-2-51,PMC1183252,15963240,CC BY,A series of frameshift mutations within the 3a gene has been observed in culture-derived severe acute respiratory syndrome coronavirus (SARS-CoV). We report here that viral RNA from clinical samples obtained from SARS-CoV infected patients also contains a heterogeneous population of wild-type and mutant 3a transcripts.,2005 Jun 20,"['Tan, Timothy HP', 'Barkham, Timothy', 'Fielding, Burtram C', 'Chou, Chih-Fong', 'Shen, Shuo', 'Lim, Seng Gee', 'Hong, Wanjin', 'Tan, Yee-Joo']",Virol J,,,True
0e68ed59a0acf6df0c5ce5a4716b907367fed3f0,PMC,Conservation of pregnancy-specific glycoprotein (PSG) N domains following independent expansions of the gene families in rodents and primates,http://dx.doi.org/10.1186/1471-2148-5-39,PMC1185527,15987510,CC BY,"BACKGROUND: Rodent and primate pregnancy-specific glycoprotein (PSG) gene families have expanded independently from a common ancestor and are expressed virtually exclusively in placental trophoblasts. However, within each species, it is unknown whether multiple paralogs have been selected for diversification of function, or for increased dosage of monofunctional PSG. We analysed the evolution of the mouse PSG sequences, and compared them to rat, human and baboon PSGs to attempt to understand the evolution of this complex gene family. RESULTS: Phylogenetic tree analyses indicate that the primate N domains and the rodent N1 domains exhibit a higher degree of conservation than that observed in a comparison of the mouse N1 and N2 domains, or mouse N1 and N3 domains. Compared to human and baboon PSG N domain exons, mouse and rat PSG N domain exons have undergone less sequence homogenisation. The high non-synonymous substitution rates observed in the CFG face of the mouse N1 domain, within a context of overall conservation, suggests divergence of function of mouse PSGs. The rat PSG family appears to have undergone less expansion than the mouse, exhibits lower divergence rates and increased sequence homogenisation in the CFG face of the N1 domain. In contrast to most primate PSG N domains, rodent PSG N1 domains do not contain an RGD tri-peptide motif, but do contain RGD-like sequences, which are not conserved in rodent N2 and N3 domains. CONCLUSION: Relative conservation of primate N domains and rodent N1 domains suggests that, despite independent gene family expansions and structural diversification, mouse and human PSGs retain conserved functions. Human PSG gene family expansion and homogenisation suggests that evolution occurred in a concerted manner that maintains similar functions of PSGs, whilst increasing gene dosage of the family as a whole. In the mouse, gene family expansion, coupled with local diversification of the CFG face, suggests selection both for increased gene dosage and diversification of function. Partial conservation of RGD and RGD-like tri-peptides in primate and rodent N and N1 domains, respectively, supports a role for these motifs in PSG function.",2005 Jun 29,"['McLellan, Andrew S', 'Zimmermann, Wolfgang', 'Moore, Tom']",BMC Evol Biol,,,True
10e691d6bf9cfc219bb72a2761d37ae5f1677f77,PMC,Croup Is Associated with the Novel Coronavirus NL63,http://dx.doi.org/10.1371/journal.pmed.0020240,PMC1188248,16104827,CC BY,"BACKGROUND: The clinical relevance of infections with the novel human coronavirus NL63 (HCoV-NL63) has not been investigated systematically. We therefore determined its association with disease in young children with lower respiratory tract infection (LRTI). METHODS AND FINDINGS: Nine hundred forty-nine samples of nasopharyngeal secretions from children under 3 y of age with LRTIs were analysed by a quantitative HCoV-NL63-specific real-time PCR. The samples had been collected from hospitalised patients and outpatients from December 1999 to October 2001 in four different regions in Germany as part of the prospective population-based PRI.DE study and analysed for RNA from respiratory viruses. Forty-nine samples (5.2%), mainly derived from the winter season, were positive for HCoV-NL63 RNA. The viral RNA was more prevalent in samples from outpatients (7.9%) than from hospitalised patients (3.2%, p = 0.003), and co-infection with either respiratory syncytial virus or parainfluenza virus 3 was observed frequently. Samples in which only HCoV-NL63 RNA could be detected had a significantly higher viral load than samples containing additional respiratory viruses (median 2.1 × 10(6) versus 2.7 × 10(2) copies/ml, p = 0.0006). A strong association with croup was apparent: 43% of the HCoV-NL63-positive patients with high HCoV-NL63 load and absence of co-infection suffered from croup, compared to 6% in the HCoV-NL63-negative group, p < 0.0001. A significantly higher fraction (17.4%) of samples from croup patients than from non-croup patients (4.2%) contained HCoV-NL63 RNA. CONCLUSION: HCoV-NL63 infections occur frequently in young children with LRTI and show a strong association with croup, suggesting a causal relationship.",2005 Aug 23,"['van der Hoek, Lia', 'Sure, Klaus', 'Ihorst, Gabriele', 'Stang, Alexander', 'Pyrc, Krzysztof', 'Jebbink, Maarten F', 'Petersen, Gudula', 'Forster, Johannes', 'Berkhout, Ben', 'Überla, Klaus']",PLoS Med,,,True
53d23d22eded7c3e0487ceeebaecb43329ba7396,PMC,A Novel Virus for Croup,http://dx.doi.org/10.1371/journal.pmed.0020274,PMC1188251,,CC0,,2005 Aug 23,,PLoS Med,,,False
30e4b834f1684fcc9ba26d41316a44b90aa287a6,PMC,G0/G1 arrest and apoptosis induced by SARS-CoV 3b protein in transfected cells,http://dx.doi.org/10.1186/1743-422X-2-66,PMC1190220,16107218,CC BY,"Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), cause of the life-threatening atypical pneumonia, infects many organs, such as lung, liver and immune organ, and induces parenchyma cells apoptosis and necrosis. The genome of SARS-CoV, not closely related to any of the previously characterized coronavirus, encodes replicase and four major structural proteins and a number of non-structural proteins. Published studies suggest that some non-structural proteins may play important roles in the replication, virulence and pathogenesis of viruses. Among the potential SARS-CoV non-structural proteins, 3b protein (ORF4) is predicted encoding 154 amino acids, lacking significant similarities to any known proteins. Till now, there is no report about the function of 3b protein. In this study, 3b gene was linked with the EGFP tag at the C- terminus. Through cell cycle analysis, it was found that over-expression of 3b-EGFP protein in Vero, 293 and COS-7 cells could induce cell cycle arrest at G0/G1 phase, and that especially in COS-7 cells, expression of 3b-EGFP was able to induce the increase of sub-G1 phase from 24 h after transfection, which was most obvious at 48 h. The apoptosis induction of 3b fusion protein in COS-7 cells was further confirmed by double cell labeling with 7-AAD and Annexin V, the function of 3b protein inducing cell G0/G1 arrest and apoptosis may provide a new insight for further study on the mechanism of SARS pathogenesis.",2005 Aug 17,"['Yuan, Xiaoling', 'Shan, Yajun', 'Zhao, Zhenhu', 'Chen, Jiapei', 'Cong, Yuwen']",Virol J,,,True
bd92cbae7179f07d59d1ce4d7ca96e37ebb40ec9,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,True
752693d2137be042f6d7e42e1aa034f5bfb95d9f,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,True
7f51cd332e57025cff78572e683429428664cf49,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,False
d8591102a5fb4a6ca07cd30418f80c913bb1000d,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,False
08a23c9d22d75baf28efcfd7aee03fdc8ed65058,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,False
a44f72e913b445c399d966da1406ff8af979a229,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,False
907ae5d1ab217c06925ef5cb0fbbf566ac06c5c7,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,False
7b52146058cfa616d16f1d86ff502bc235175fd3,PMC,Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030324,PMC1197287,16128623,CC BY,"The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.",2005 Oct 6,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,False
a9b8e1cd354483fc8d7825a2ba27d4e7c16c56ce,PMC,Casting a Wide Net to Fight Coronaviruses,http://dx.doi.org/10.1371/journal.pbio.0030353,PMC1197291,,CC BY,,2005 Oct 6,,PLoS Biol,,,False
0450e1d435d63e69e1867c2eba65c0c08af70038,PMC,Phosphatidylserine treatment relieves the block to retrovirus infection of cells expressing glycosylated virus receptors,http://dx.doi.org/10.1186/1742-4690-2-49,PMC1201173,16091143,CC BY,"BACKGROUND: A major determinant of retrovirus host range is the presence or absence of appropriate cell-surface receptors required for virus entry. Often orthologs of functional receptors are present in a wide range of species, but amino acid differences can render these receptors non-functional. In some cases amino acid differences result in additional N-linked glycosylation that blocks virus infection. The latter block to retrovirus infection can be overcome by treatment of cells with compounds such as tunicamycin, which prevent the addition of N-linked oligosaccharides. RESULTS: We have discovered that treatment of cells with liposomes composed of phosphatidylserine (PS) can also overcome the block to infection mediated by N-linked glycosylation. Importantly, this effect occurs without apparent change in the glycosylation state of the receptors for these viruses. This effect occurs with delayed kinetics compared to previous results showing enhancement of virus infection by PS treatment of cells expressing functional virus receptors. CONCLUSION: We have demonstrated that PS treatment can relieve the block to retrovirus infection of cells expressing retroviral receptors that have been rendered non-functional by glycosylation. These findings have important implications for the current model describing inhibition of virus entry by receptor glycosylation.",2005 Aug 9,"['Coil, David A', 'Miller, A Dusty']",Retrovirology,,,True
4e1a080ea558bba7654e05d59ed0b6c6e686b66e,PMC,A new paradigm in respiratory hygiene: increasing the cohesivity of airway secretions to improve cough interaction and reduce aerosol dispersion,http://dx.doi.org/10.1186/1471-2466-5-11,PMC1208914,16138926,CC BY,"BACKGROUND: Infectious respiratory diseases are transmitted to non-infected subjects when an infected person expels pathogenic microorganisms to the surrounding environment when coughing or sneezing. When the airway mucus layer interacts with high-speed airflow, droplets are expelled as aerosol; their concentration and size distribution may each play an important role in disease transmission. Our goal is to reduce the aerosolizability of respiratory secretions while interfering only minimally with normal mucus clearance using agents capable of increasing crosslinking in the mucin glycoprotein network. METHODS: We exposed mucus simulants (MS) to airflow in a simulated cough machine (SCM). The MS ranged from non-viscous, non-elastic substances (water) to MS of varying degrees of viscosity and elasticity. Mucociliary clearance of the MS was assessed on the frog palate, elasticity in the Filancemeter and the aerosol pattern in a ""bulls-eye"" target. The sample loaded was weighed before and after each cough maneuver. We tested two mucomodulators: sodium tetraborate (XL""B"") and calcium chloride (XL ""C""). RESULTS: Mucociliary transport was close to normal speed in viscoelastic samples compared to non-elastic, non-viscous or viscous-only samples. Spinnability ranged from 2.5 ± 0.6 to 50.9 ± 6.9 cm, and the amount of MS expelled from the SCM increased from 47 % to 96 % adding 1.5 μL to 150 μL of XL ""B"". Concurrently, particles were inversely reduced to almost disappear from the aerosolization pattern. CONCLUSION: The aerosolizability of MS was modified by increasing its cohesivity, thereby reducing the number of particles expelled from the SCM while interfering minimally with its clearance on the frog palate. An unexpected finding is that MS crosslinking increased ""expectoration"".",2005 Sep 2,"['Zayas, Gustavo', 'Dimitry, John', 'Zayas, Ana', ""O'Brien, Darryl"", 'King, Malcolm']",BMC Pulm Med,,,True
60666795212b915f165db9762a95445be1fb2bad,PMC,The health impacts of globalisation: a conceptual framework,http://dx.doi.org/10.1186/1744-8603-1-14,PMC1208931,16078989,CC BY,"This paper describes a conceptual framework for the health implications of globalisation. The framework is developed by first identifying the main determinants of population health and the main features of the globalisation process. The resulting conceptual model explicitly visualises that globalisation affects the institutional, economic, social-cultural and ecological determinants of population health, and that the globalisation process mainly operates at the contextual level, while influencing health through its more distal and proximal determinants. The developed framework provides valuable insights in how to organise the complexity involved in studying the health effects resulting from globalisation. It could, therefore, give a meaningful contribution to further empirical research by serving as a 'think-model' and provides a basis for the development of future scenarios on health.",2005 Aug 3,"['Huynen, Maud MTE', 'Martens, Pim', 'Hilderink, Henk BM']",Global Health,,,True
d1d7471ec350b7a5839863b90218a6c0b9596e85,PMC,The potential impact of the next influenza pandemic on a national primary care medical workforce,http://dx.doi.org/10.1186/1478-4491-3-7,PMC1215505,16092972,CC BY,"BACKGROUND: Another influenza pandemic is all but inevitable. We estimated its potential impact on the primary care medical workforce in New Zealand, so that planning could mitigate the disruption from the pandemic and similar challenges. METHODS: The model in the ""FluAid"" software (Centers for Disease Control and Prevention, CDC, Atlanta) was applied to the New Zealand primary care medical workforce (i.e., general practitioners). RESULTS: At its peak (week 4) the pandemic would lead to 1.2% to 2.7% loss of medical work time, using conservative baseline assumptions. Most workdays (88%) would be lost due to illness, followed by hospitalisation (8%), and then premature death (4%). Inputs for a ""more severe"" scenario included greater health effects and time spent caring for sick relatives. For this scenario, 9% of medical workdays would be lost in the peak week, and 3% over a more compressed six-week period of the first pandemic wave. As with the base case, most (64%) of lost workdays would be due to illness, followed by caring for others (31%), hospitalisation (4%), and then premature death (1%). CONCLUSION: Preparedness planning for future influenza pandemics must consider the impact on this medical workforce and incorporate strategies to minimise this impact, including infection control measures, well-designed protocols, and improved health sector surge capacity.",2005 Aug 11,"['Wilson, Nick', 'Baker, Michael', 'Crampton, Peter', 'Mansoor, Osman']",Hum Resour Health,,,True
33f0a6576216e3c8ff02dcb1affaa66c9f08e30b,PMC,Macrophages and cytokines in the early defence against herpes simplex virus,http://dx.doi.org/10.1186/1743-422X-2-59,PMC1215526,16076403,CC BY,"Herpes simplex virus (HSV) type 1 and 2 are old viruses, with a history of evolution shared with humans. Thus, it is generally well-adapted viruses, infecting many of us without doing much harm, and with the capacity to hide in our neurons for life. In rare situations, however, the primary infection becomes generalized or involves the brain. Normally, the primary HSV infection is asymptomatic, and a crucial element in the early restriction of virus replication and thus avoidance of symptoms from the infection is the concerted action of different arms of the innate immune response. An early and light struggle inhibiting some HSV replication will spare the host from the real war against huge amounts of virus later in infection. As far as such a war will jeopardize the life of the host, it will be in both interests, including the virus, to settle the conflict amicably. Some important weapons of the unspecific defence and the early strikes and beginning battle during the first days of a HSV infection are discussed in this review. Generally, macrophages are orchestrating a multitude of anti-herpetic actions during the first hours of the attack. In a first wave of responses, cytokines, primarily type I interferons (IFN) and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. In the next wave, interleukin (IL)-12 together with the above and other cytokines induce production of IFN-γ in mainly NK cells. Many positive feed-back mechanisms and synergistic interactions intensify these systems and give rise to heavy antiviral weapons such as reactive oxygen species and nitric oxide. This results in the generation of an alliance against the viral enemy. However, these heavy weapons have to be controlled to avoid too much harm to the host. By IL-4 and others, these reactions are hampered, but they are still allowed in foci of HSV replication, thus focusing the activity to only relevant sites. So, no hero does it alone. Rather, an alliance of cytokines, macrophages and other cells seems to play a central role. Implications of this for future treatment modalities are shortly considered.",2005 Aug 3,"Ellermann-Eriksen, Svend",Virol J,,,True
7d6a4a17160dee1235864e5860da782093e4d07b,PMC,"Patterns of HIV prevalence among injecting drug users in the cross-border area of Lang Son Province, Vietnam, and Ning Ming County, Guangxi Province, China",http://dx.doi.org/10.1186/1471-2458-5-89,PMC1232855,16120225,CC BY,"BACKGROUND: To assess patterns of injecting drug use and HIV prevalence among injecting drug users (IDUs) in an international border area along a major heroin trans-shipment route. METHODS: Cross-sectional surveys of IDUs in 5 sites in Lang Son Province, Vietnam (n = 348) and 3 sites in Ning Ming County, Guangxi Province, China (n = 308). Respondents were recruited through peer referral (""snowball"") methods in both countries, and also from officially recorded lists of IDUs in Vietnam. A risk behavior questionnaire was administered and HIV counseling and testing conducted. RESULTS: Participants in both countries were largely male, in their 20s, and unmarried. A majority of subjects in both countries were members of ethnic minority groups. There were strong geographic gradients for length of drug injecting and for HIV seroprevalence. Both mean years injecting and HIV seroprevalence declined from the Vietnamese site farthest from the border to the Chinese site farthest from the border. 10.6% of participants in China and 24.5% of participants in Vietnam reported crossing the international border in the 6 months prior to interview. Crossing the border by IDUs was associated with (1) distance from the border, (2) being a member of an ethnic minority group, and (3) being HIV seropositive among Chinese participants. CONCLUSION: Reducing the international spread of HIV among IDUs will require programs at the global, regional, national, and ""local cross border"" levels. At the local cross border level, the programs should be coordinated on both sides of the border and on a sufficient scale that IDUs will be able to readily obtain clean injection equipment on the other side of the border as well as in their country of residence.",2005 Aug 24,"['Des Jarlais, Don C', 'Johnston, Patrick', 'Friedmann, Patricia', 'Kling, Ryan', 'Liu, Wei', 'Ngu, Doan', 'Chen, Yi', 'Hoang, Tran V', 'Donghua, Meng', 'Van, Ly K', 'Tung, Nguyen D', 'Binh, Kieu T', 'Hammett, Theodore M']",BMC Public Health,,,True
a4b16ad01125dda3a5dd4ae97fe8cb53c9538075,PMC,Chloroquine is a potent inhibitor of SARS coronavirus infection and spread,http://dx.doi.org/10.1186/1743-422X-2-69,PMC1232869,16115318,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS) is caused by a newly discovered coronavirus (SARS-CoV). No effective prophylactic or post-exposure therapy is currently available. RESULTS: We report, however, that chloroquine has strong antiviral effects on SARS-CoV infection of primate cells. These inhibitory effects are observed when the cells are treated with the drug either before or after exposure to the virus, suggesting both prophylactic and therapeutic advantage. In addition to the well-known functions of chloroquine such as elevations of endosomal pH, the drug appears to interfere with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2. This may negatively influence the virus-receptor binding and abrogate the infection, with further ramifications by the elevation of vesicular pH, resulting in the inhibition of infection and spread of SARS CoV at clinically admissible concentrations. CONCLUSION: Chloroquine is effective in preventing the spread of SARS CoV in cell culture. Favorable inhibition of virus spread was observed when the cells were either treated with chloroquine prior to or after SARS CoV infection. In addition, the indirect immunofluorescence assay described herein represents a simple and rapid method for screening SARS-CoV antiviral compounds.",2005 Aug 22,"['Vincent, Martin J', 'Bergeron, Eric', 'Benjannet, Suzanne', 'Erickson, Bobbie R', 'Rollin, Pierre E', 'Ksiazek, Thomas G', 'Seidah, Nabil G', 'Nichol, Stuart T']",Virol J,,,True
3bd02864e1ab4b40712401ac5a0c8580dc98c0c9,PMC,The SARS Coronavirus S Glycoprotein Receptor Binding Domain: Fine Mapping and Functional Characterization,http://dx.doi.org/10.1186/1743-422X-2-73,PMC1236967,16122388,CC BY,"The entry of the SARS coronavirus (SCV) into cells is initiated by binding of its spike envelope glycoprotein (S) to a receptor, ACE2. We and others identified the receptor-binding domain (RBD) by using S fragments of various lengths but all including the amino acid residue 318 and two other potential glycosylation sites. To further characterize the role of glycosylation and identify residues important for its function as an interacting partner of ACE2, we have cloned, expressed and characterized various soluble fragments of S containing RBD, and mutated all potential glycosylation sites and 32 other residues. The shortest of these fragments still able to bind the receptor ACE2 did not include residue 318 (which is a potential glycosylation site), but started at residue 319, and has only two potential glycosylation sites (residues 330 and 357). Mutation of each of these sites to either alanine or glutamine, as well as mutation of residue 318 to alanine in longer fragments resulted in the same decrease of molecular weight (by approximately 3 kDa) suggesting that all glycosylation sites are functional. Simultaneous mutation of all glycosylation sites resulted in lack of expression suggesting that at least one glycosylation site (any of the three) is required for expression. Glycosylation did not affect binding to ACE2. Alanine scanning mutagenesis of the fragment S319–518 resulted in the identification of ten residues (K390, R426, D429, T431, I455, N473, F483, Q492, Y494, R495) that significantly reduced binding to ACE2, and one residue (D393) that appears to increase binding. Mutation of residue T431 reduced binding by about 2-fold, and mutation of the other eight residues – by more than 10-fold. Analysis of these data and the mapping of these mutations on the recently determined crystal structure of a fragment containing the RBD complexed to ACE2 (Li, F, Li, W, Farzan, M, and Harrison, S. C., submitted) suggested the existence of two hot spots on the S RBD surface, R426 and N473, which are likely to contribute significant portion of the binding energy. The finding that most of the mutations (23 out of 34 including glycosylation sites) do not affect the RBD binding function indicates possible mechanisms for evasion of immune responses.",2005 Aug 25,"['Chakraborti, Samitabh', 'Prabakaran, Ponraj', 'Xiao, Xiaodong', 'Dimitrov, Dimiter S']",Virol J,,,True
c49e3b42331dd3c65340f486f5b6067df16cbbd4,PMC,E-Predict: a computational strategy for species identification based on observed DNA microarray hybridization patterns,http://dx.doi.org/10.1186/gb-2005-6-9-r78,PMC1242213,16168085,CC BY,"DNA microarrays may be used to identify microbial species present in environmental and clinical samples. However, automated tools for reliable species identification based on observed microarray hybridization patterns are lacking. We present an algorithm, E-Predict, for microarray-based species identification. E-Predict compares observed hybridization patterns with theoretical energy profiles representing different species. We demonstrate the application of the algorithm to viral detection in a set of clinical samples and discuss its relevance to other metagenomic applications.",2005 Aug 30,"['Urisman, Anatoly', 'Fischer, Kael F', 'Chiu, Charles Y', 'Kistler, Amy L', 'Beck, Shoshannah', 'Wang, David', 'DeRisi, Joseph L']",Genome Biol,,,True
29d776d7a6f03cf59887534629dcbe5014f09aed,PMC,"Web GIS in practice III: creating a simple interactive map of England's Strategic Health Authorities using Google Maps API, Google Earth KML, and MSN Virtual Earth Map Control",http://dx.doi.org/10.1186/1476-072X-4-22,PMC1242244,16176577,CC BY,"This eye-opener article aims at introducing the health GIS community to the emerging online consumer geoinformatics services from Google and Microsoft (MSN), and their potential utility in creating custom online interactive health maps. Using the programmable interfaces provided by Google and MSN, we created three interactive demonstrator maps of England's Strategic Health Authorities. These can be browsed online at – Google Maps API (Application Programming Interface) version, – Google Earth KML (Keyhole Markup Language) version, and – MSN Virtual Earth Map Control version. Google and MSN's worldwide distribution of ""free"" geospatial tools, imagery, and maps is to be commended as a significant step towards the ultimate ""wikification"" of maps and GIS. A discussion is provided of these emerging online mapping trends, their expected future implications and development directions, and associated individual privacy, national security and copyrights issues. Although ESRI have announced their planned response to Google (and MSN), it remains to be seen how their envisaged plans will materialize and compare to the offerings from Google and MSN, and also how Google and MSN mapping tools will further evolve in the near future.",2005 Sep 21,"Boulos, Maged N Kamel",Int J Health Geogr,,,True
5b3e895eea9402eca728dbe11b00431d4bacbc7f,PMC,The National Children’s Study: A Critical National Investment,,PMC1247577,15471708,CC0,,2004 Oct,"['Trasande, Leonardo', 'Landrigan, Philip J.']",Environ Health Perspect,,,True
a3c3b7c38ad32e1042d78aae2027ca491e9f2197,PMC,Understanding the Spatial Clustering of Severe Acute Respiratory Syndrome (SARS) in Hong Kong,http://dx.doi.org/10.1289/ehp.7117,PMC1247620,15531441,CC0,"We applied cartographic and geostatistical methods in analyzing the patterns of disease spread during the 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong using geographic information system (GIS) technology. We analyzed an integrated database that contained clinical and personal details on all 1,755 patients confirmed to have SARS from 15 February to 22 June 2003. Elementary mapping of disease occurrences in space and time simultaneously revealed the geographic extent of spread throughout the territory. Statistical surfaces created by the kernel method confirmed that SARS cases were highly clustered and identified distinct disease “hot spots.” Contextual analysis of mean and standard deviation of different density classes indicated that the period from day 1 (18 February) through day 16 (6 March) was the prodrome of the epidemic, whereas days 86 (15 May) to 106 (4 June) marked the declining phase of the outbreak. Origin-and-destination plots showed the directional bias and radius of spread of superspreading events. Integration of GIS technology into routine field epidemiologic surveillance can offer a real-time quantitative method for identifying and tracking the geospatial spread of infectious diseases, as our experience with SARS has demonstrated.",2004 Nov 27,"['Lai, P.C.', 'Wong, C.M.', 'Hedley, A.J.', 'Lo, S.V.', 'Leung, P.Y.', 'Kong, J.', 'Leung, G.M.']",Environ Health Perspect,,,True
87ad4bcfb14f3ae9f7eb1a0642d50fad167349e2,PMC,The Big Picture,,PMC1247652,,CC0,,2004 Nov,"Alderson, Laura",Environ Health Perspect,,,True
5227121ac5523e669cc04c9a8f2660080d995a34,PMC,A combined nucleocapsid vaccine induces vigorous SARS-CD8+ T-cell immune responses,http://dx.doi.org/10.1186/1479-0556-3-7,PMC1249587,16115319,CC BY,"Several studies have shown that cell-mediated immune responses play a crucial role in controlling viral replication. As such, a candidate SARS vaccine should elicit broad CD8+ T-cell immune responses. Several groups of mice were immunized alone or in combination with SARS-nucleocapsid immunogen. A high level of specific SARS-CD8+ T-cell response was demonstrated in mice that received DNA encoding the SARS-nucleocapsid, protein and XIAP as an adjuvant. We also observed that co-administration of a plasmid expressing nucleocapsid, recombinant protein and montanide/CpG induces high antibody titers in immunized mice. Moreover, this vaccine approach merits further investigation as a potential candidate vaccine against SARS.",2005 Aug 22,"['Azizi, Ali', 'Aucoin, Susan', 'Tadesse, Helina', 'Frost, Rita', 'Ghorbani, Masoud', 'Soare, Catalina', 'Naas, Turaya', 'Diaz-Mitoma, Francisco']",Genet Vaccines Ther,,,True
c1c6a98c21304f3788b20870b34afd8a115fa38c,PMC,The Application of the Haddon Matrix to Public Health Readiness and Response Planning,http://dx.doi.org/10.1289/ehp.7491,PMC1257548,15866764,CC0,"State and local health departments continue to face unprecedented challenges in preparing for, recognizing, and responding to threats to the public’s health. The attacks of 11 September 2001 and the ensuing anthrax mailings of 2001 highlighted the public health readiness and response hurdles posed by intentionally caused injury and illness. At the same time, recent natural disasters have highlighted the need for comparable public health readiness and response capabilities. Public health readiness and response activities can be conceptualized similarly for intentional attacks, natural disasters, and human-caused accidents. Consistent with this view, the federal government has adopted the all-hazards response model as its fundamental paradigm. Adoption of this paradigm provides powerful improvements in efficiency and efficacy, because it reduces the need to create a complex family of situation-specific preparedness and response activities. However, in practice, public health preparedness requires additional models and tools to provide a framework to better understand and prioritize emergency readiness and response needs, as well as to facilitate solutions; this is particularly true at the local health department level. Here, we propose to extend the use of the Haddon matrix—a conceptual model used for more than two decades in injury prevention and response strategies—for this purpose.",2005 May 2,"['Barnett, Daniel J.', 'Balicer, Ran D.', 'Blodgett, David', 'Fews, Ayanna L.', 'Parker, Cindy L.', 'Links, Jonathan M.']",Environ Health Perspect,,,True
9b960b5f7c871b2dbb4ee3ba78392ca6a333224b,PMC,"Replicative homeostasis II: Influence of polymerase fidelity on RNA virus quasispecies biology: Implications for immune recognition, viral autoimmunity and other ""virus receptor"" diseases",http://dx.doi.org/10.1186/1743-422X-2-70,PMC1260030,16115320,CC BY,"Much of the worlds' population is in active or imminent danger from established infectious pathogens, while sporadic and pandemic infections by these and emerging agents threaten everyone. RNA polymerases (RNA(pol)) generate enormous genetic and consequent antigenic heterogeneity permitting both viruses and cellular pathogens to evade host defences. Thus, RNA(pol )causes more morbidity and premature mortality than any other molecule. The extraordinary genetic heterogeneity defining viral quasispecies results from RNA(pol )infidelity causing rapid cumulative genomic RNA mutation a process that, if uncontrolled, would cause catastrophic loss of sequence integrity and inexorable quasispecies extinction. Selective replication and replicative homeostasis, an epicyclical regulatory mechanism dynamically linking RNApol fidelity and processivity with quasispecies phenotypic diversity, modulating polymerase fidelity and, hence, controlling quasispecies behaviour, prevents this happening and also mediates immune escape. Perhaps more importantly, ineluctable generation of broad phenotypic diversity after viral RNA is translated to protein quasispecies suggests a mechanism of disease that specifically targets, and functionally disrupts, the host cell surface molecules – including hormone, lipid, cell signalling or neurotransmitter receptors – that viruses co-opt for cell entry. This mechanism – ""Viral Receptor Disease (VRD)"" – may explain so-called ""viral autoimmunity"", some classical autoimmune disorders and other diseases, including type II diabetes mellitus, and some forms of obesity. Viral receptor disease is a unifying hypothesis that may also explain some diseases with well-established, but multi-factorial and apparently unrelated aetiologies – like coronary artery and other vascular diseases – in addition to diseases like schizophrenia that are poorly understood and lack plausible, coherent, pathogenic explanations.",2005 Aug 22,"Sallie, Richard",Virol J,,,True
d6ea8e153027d428bc443df40d70bfa2134a2deb,PMC,Generation of human antibody fragments recognizing distinct epitopes of the nucleocapsid (N) SARS-CoV protein using a phage display approach,http://dx.doi.org/10.1186/1471-2334-5-73,PMC1261265,16171519,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS)-CoV is a newly emerging virus that causes SARS with high mortality rate in infected people. Successful control of the global SARS epidemic will require rapid and sensitive diagnostic tests to monitor its spread, as well as, the development of vaccines and new antiviral compounds including neutralizing antibodies that effectively prevent or treat this disease. METHODS: The human synthetic single-chain fragment variable (scFv) ETH-2 phage antibody library was used for the isolation of scFvs against the nucleocapsid (N) protein of SARS-CoV using a bio panning-based strategy. The selected scFvs were characterized under genetics-molecular aspects and for SARS-CoV N protein detection in ELISA, western blotting and immunocytochemistry. RESULTS: Human scFv antibodies to N protein of SARS-CoV can be easily isolated by selecting the ETH-2 phage library on immunotubes coated with antigen. These in vitro selected human scFvs specifically recognize in ELISA and western blotting studies distinct epitopes in N protein domains and detect in immunohistochemistry investigations SARS-CoV particles in infected Vero cells. CONCLUSION: The human scFv antibodies isolated and described in this study represent useful reagents for rapid detection of N SARS-CoV protein and SARS virus particles in infected target cells.",2005 Sep 19,"['Flego, Michela', 'Di Bonito, Paola', 'Ascione, Alessandro', 'Zamboni, Silvia', 'Carattoli, Alessandra', 'Grasso, Felicia', 'Cassone, Antonio', 'Cianfriglia, Maurizio']",BMC Infect Dis,,,True
79da8c8e26960026682cb2daf09ec3357b1bec5a,PMC,Molecular signature of clinical severity in recovering patients with severe acute respiratory syndrome coronavirus (SARS-CoV),http://dx.doi.org/10.1186/1471-2164-6-132,PMC1262710,16174304,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS), a recent epidemic human disease, is caused by a novel coronavirus (SARS-CoV). First reported in Asia, SARS quickly spread worldwide through international travelling. As of July 2003, the World Health Organization reported a total of 8,437 people afflicted with SARS with a 9.6% mortality rate. Although immunopathological damages may account for the severity of respiratory distress, little is known about how the genome-wide gene expression of the host changes under the attack of SARS-CoV. RESULTS: Based on changes in gene expression of peripheral blood, we identified 52 signature genes that accurately discriminated acute SARS patients from non-SARS controls. While a general suppression of gene expression predominated in SARS-infected blood, several genes including those involved in innate immunity, such as defensins and eosinophil-derived neurotoxin, were upregulated. Instead of employing clustering methods, we ranked the severity of recovering SARS patients by generalized associate plots (GAP) according to the expression profiles of 52 signature genes. Through this method, we discovered a smooth transition pattern of severity from normal controls to acute SARS patients. The rank of SARS severity was significantly correlated with the recovery period (in days) and with the clinical pulmonary infection score. CONCLUSION: The use of the GAP approach has proved useful in analyzing the complexity and continuity of biological systems. The severity rank derived from the global expression profile of significantly regulated genes in patients may be useful for further elucidating the pathophysiology of their disease.",2005 Sep 21,"['Lee, Yun-Shien', 'Chen, Chun-Houh', 'Chao, Angel', 'Chen, En-Shih', 'Wei, Min-Li', 'Chen, Lung-Kun', 'Yang, Kuender D', 'Lin, Meng-Chih', 'Wang, Yi-Hsi', 'Liu, Jien-Wei', 'Eng, Hock-Liew', 'Chiang, Ping-Cherng', 'Wu, Ting-Shu', 'Tsao, Kuo-Chein', 'Huang, Chung-Guei', 'Tien, Yin-Jing', 'Wang, Tzu-Hao', 'Wang, Hsing-Shih', 'Lee, Ying-Shiung']",BMC Genomics,,,True
e6d533faf65d64332697077b71aa71dfc78fc06a,PMC,The effects of injection of bovine vaccine into a human digit: a case report,http://dx.doi.org/10.1186/1476-069X-4-21,PMC1262740,16219096,CC BY,BACKGROUND: The incidence of needlestick injuries in farmers and veterinary surgeons is significant and the consequences of such an injection can be serious. CASE PRESENTATION: We report accidental injection of bovine vaccine into the base of the little finger. This resulted in increased pressure in the flexor sheath causing signs and symptoms of ischemia. Amputation of the digit was required despite repeated surgical debridement and decompression. CONCLUSION: There have been previous reports of injection of oil-based vaccines into the human hand resulting in granulomatous inflammation or sterile abscess and causing morbidity and tissue loss. Self-injection with veterinary vaccines is an occupational hazard for farmers and veterinary surgeons. Injection of vaccine into a closed compartment such as the human finger can have serious sequelae including loss of the injected digit. These injuries are not to be underestimated. Early debridement and irrigation of the injected area with decompression is likely to give the best outcome. Frequent review is necessary after the first procedure because repeat operations may be required.,2005 Oct 11,"[""O'Neill, Jennifer K"", 'Richards, Simon W', 'Ricketts, David M', 'Patterson, Marc H']",Environ Health,,,True
9f63ebfaab049c0968d72166761217b3aaa1fe00,PMC,Pneumothorax and mortality in the mechanically ventilated SARS patients: a prospective clinical study,http://dx.doi.org/10.1186/cc3736,PMC1269458,16137358,CC BY,"INTRODUCTION: Pneumothorax often complicates the management of mechanically ventilated severe acute respiratory syndrome (SARS) patients in the isolation intensive care unit (ICU). We sought to determine whether pneumothoraces are induced by high ventilatory pressure or volume and if they are associated with mortality in mechanically ventilated SARS patients. METHODS: We conducted a prospective, clinical study. Forty-one mechanically ventilated SARS patients were included in our study. All SARS patients were sedated and received mechanical ventilation in the isolation ICU. RESULTS: The mechanically ventilated SARS patients were divided into two groups either with or without pneumothorax. Their demographic data, clinical characteristics, ventilatory variables such as positive end-expiratory pressure, peak inspiratory pressure, mean airway pressure, tidal volume, tidal volume per kilogram, respiratory rate and minute ventilation and the accumulated mortality rate at 30 days after mechanical ventilation were analyzed. There were no statistically significant differences in the pressures and volumes between the two groups, and the mortality was also similar between the groups. However, patients developing pneumothorax during mechanical ventilation frequently expressed higher respiratory rates on admission, and a lower PaO(2)/FiO(2 )ratio and higher PaCO(2 )level during hospitalization compared with those without pneumothorax. CONCLUSION: In our study, the SARS patients who suffered pneumothorax presented as more tachypnic on admission, and more pronounced hypoxemic and hypercapnic during hospitalization. These variables signaled a deterioration in respiratory function and could be indicators of developing pneumothorax during mechanical ventilation in the SARS patients. Meanwhile, meticulous respiratory therapy and monitoring were mandatory in these patients.",2005 Jun 22,"['Kao, Hsin-Kuo', 'Wang, Jia-Horng', 'Sung, Chun-Sung', 'Huang, Ying-Che', 'Lien, Te-Cheng']",Crit Care,,,True
5b13e81ee4495ff3eccaeea21f955ebc5e5cbde1,PMC,Using autoregressive integrated moving average (ARIMA) models to predict and monitor the number of beds occupied during a SARS outbreak in a tertiary hospital in Singapore,http://dx.doi.org/10.1186/1472-6963-5-36,PMC1274243,15885149,CC BY,"BACKGROUND: The main objective of this study is to apply autoregressive integrated moving average (ARIMA) models to make real-time predictions on the number of beds occupied in Tan Tock Seng Hospital, during the recent SARS outbreak. METHODS: This is a retrospective study design. Hospital admission and occupancy data for isolation beds was collected from Tan Tock Seng hospital for the period 14(th )March 2003 to 31(st )May 2003. The main outcome measure was daily number of isolation beds occupied by SARS patients. Among the covariates considered were daily number of people screened, daily number of people admitted (including observation, suspect and probable cases) and days from the most recent significant event discovery. We utilized the following strategy for the analysis. Firstly, we split the outbreak data into two. Data from 14(th )March to 21(st )April 2003 was used for model development. We used structural ARIMA models in an attempt to model the number of beds occupied. Estimation is via the maximum likelihood method using the Kalman filter. For the ARIMA model parameters, we considered the simplest parsimonious lowest order model. RESULTS: We found that the ARIMA (1,0,3) model was able to describe and predict the number of beds occupied during the SARS outbreak well. The mean absolute percentage error (MAPE) for the training set and validation set were 5.7% and 8.6% respectively, which we found was reasonable for use in the hospital setting. Furthermore, the model also provided three-day forecasts of the number of beds required. Total number of admissions and probable cases admitted on the previous day were also found to be independent prognostic factors of bed occupancy. CONCLUSION: ARIMA models provide useful tools for administrators and clinicians in planning for real-time bed capacity during an outbreak of an infectious disease such as SARS. The model could well be used in planning for bed-capacity during outbreaks of other infectious diseases as well.",2005 May 11,"['Earnest, Arul', 'Chen, Mark I', 'Ng, Donald', 'Sin, Leo Yee']",BMC Health Serv Res,,,True
e2b435104da658ed6518247430cff1d428aae830,PMC,A simple and rapid approach for screening of SARS-coronavirus genotypes: an evaluation study,http://dx.doi.org/10.1186/1471-2334-5-87,PMC1276795,16229749,CC BY,"BACKGROUND: The Severe Acute Respiratory Syndrome (SARS) was a newly emerged infectious disease which caused a global epidemic in 2002–2003. Sequence analysis of SARS-coronavirus isolates revealed that specific genotypes predominated at different periods of the epidemic. This information can be used as a footprint for tracing the epidemiology of infections and monitor viral evolution. However, direct sequencing analysis of a large number of clinical samples is cumbersome and time consuming. We present here a simple and rapid assay for the screening of SARS-coronavirus genotypes based on the use of fluorogenic oligonucleotide probes for allelic discrimination. METHODS: Thirty SARS patients were recruited. Allelic discrimination assays were developed based on the use of fluorogenic oligonucleotide probes (TaqMan). Genotyping of the SARS-coronavirus isolates obtained from these patients were carried out by the allelic discrimination assays and confirmed by direct sequencing. RESULTS: Genotyping based on the allelic discrimination assays were fully concordant with direct sequencing. All of the 30 SARS-coronavirus genotypes studied were characteristic of genotypes previously documented to be associated with the latter part of the epidemic. Seven of the isolates contained a previously reported major deletion but in patients not epidemiologically related to the previously studied cohort. CONCLUSION: We have developed a simple and accurate method for the characterization and screening of SARS-coronavirus genotypes. It is a promising tool for the study of epidemiological relationships between documented cases during an outbreak.",2005 Oct 18,"['Chung, Grace TY', 'Chiu, Rossa WK', 'Cheung, Jo LK', 'Jin, Yongjie', 'Chim, Stephen SC', 'Chan, Paul KS', 'Lo, YM Dennis']",BMC Infect Dis,,,True
4c2205dd9943bdc4547fb999c6616269df83c685,PMC,Errata,,PMC1278499,,CC0,,2005 Apr,,Environ Health Perspect,,,True
c64fa46231a266d52eb5c7927dee12f7d55ae1b1,PMC,Correction: Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,http://dx.doi.org/10.1371/journal.pbio.0030428,PMC1283410,,CC BY,,2005 Nov 15,"['Yang, Haitao', 'Xie, Weiqing', 'Xue, Xiaoyu', 'Yang, Kailin', 'Ma, Jing', 'Liang, Wenxue', 'Zhao, Qi', 'Zhou, Zhe', 'Pei, Duanqing', 'Ziebuhr, John', 'Hilgenfeld, Rolf', 'Yuen, Kwok Yung', 'Wong, Luet', 'Gao, Guangxia', 'Chen, Saijuan', 'Chen, Zhu', 'Ma, Dawei', 'Bartlam, Mark', 'Rao, Zihe']",PLoS Biol,,,False
1c7b536966e355206379e97fd0e8ef71d71fb143,PMC,The Difficulties of Predicting the Outbreak Sizes of Epidemics,http://dx.doi.org/10.1371/journal.pmed.0030023,PMC1285070,,CC BY,,2006 Jan 22,,PLoS Med,,,True
ae19236936b05793ceac08ed5d58269c25486320,PMC,An ontology for immune epitopes: application to the design of a broad scope database of immune reactivities,http://dx.doi.org/10.1186/1745-7580-1-2,PMC1287064,16305755,CC BY,"BACKGROUND: Epitopes can be defined as the molecular structures bound by specific receptors, which are recognized during immune responses. The Immune Epitope Database and Analysis Resource (IEDB) project will catalog and organize information regarding antibody and T cell epitopes from infectious pathogens, experimental antigens and self-antigens, with a priority on NIAID Category A-C pathogens () and emerging/re-emerging infectious diseases. Both intrinsic structural and phylogenetic features, as well as information relating to the interactions of the epitopes with the host's immune system will be catalogued. DESCRIPTION: To effectively represent and communicate the information related to immune epitopes, a formal ontology was developed. The semantics of the epitope domain and related concepts were captured as a hierarchy of classes, which represent the general and specialized relationships between the various concepts. A complete listing of classes and their properties can be found at . CONCLUSION: The IEDB's ontology is the first ontology specifically designed to capture both intrinsic chemical and biochemical information relating to immune epitopes with information relating to the interaction of these structures with molecules derived from the host immune system. We anticipate that the development of this type of ontology and associated databases will facilitate rigorous description of data related to immune epitopes, and might ultimately lead to completely new methods for describing and modeling immune responses.",2005 Sep 20,"['Sathiamurthy, Muthuraman', 'Peters, Bjoern', 'Bui, Huynh-Hoa', 'Sidney, John', 'Mokili, John', 'Wilson, Stephen S', 'Fleri, Ward', 'McGuinness, Deborah L', 'Bourne, Philip E', 'Sette, Alessandro']",Immunome Res,,,True
db04140e4d00bc73a1f417761c2b84c3e5c53d73,PMC,An ontology for immune epitopes: application to the design of a broad scope database of immune reactivities,http://dx.doi.org/10.1186/1745-7580-1-2,PMC1287064,16305755,CC BY,"BACKGROUND: Epitopes can be defined as the molecular structures bound by specific receptors, which are recognized during immune responses. The Immune Epitope Database and Analysis Resource (IEDB) project will catalog and organize information regarding antibody and T cell epitopes from infectious pathogens, experimental antigens and self-antigens, with a priority on NIAID Category A-C pathogens () and emerging/re-emerging infectious diseases. Both intrinsic structural and phylogenetic features, as well as information relating to the interactions of the epitopes with the host's immune system will be catalogued. DESCRIPTION: To effectively represent and communicate the information related to immune epitopes, a formal ontology was developed. The semantics of the epitope domain and related concepts were captured as a hierarchy of classes, which represent the general and specialized relationships between the various concepts. A complete listing of classes and their properties can be found at . CONCLUSION: The IEDB's ontology is the first ontology specifically designed to capture both intrinsic chemical and biochemical information relating to immune epitopes with information relating to the interaction of these structures with molecules derived from the host immune system. We anticipate that the development of this type of ontology and associated databases will facilitate rigorous description of data related to immune epitopes, and might ultimately lead to completely new methods for describing and modeling immune responses.",2005 Sep 20,"['Sathiamurthy, Muthuraman', 'Peters, Bjoern', 'Bui, Huynh-Hoa', 'Sidney, John', 'Mokili, John', 'Wilson, Stephen S', 'Fleri, Ward', 'McGuinness, Deborah L', 'Bourne, Philip E', 'Sette, Alessandro']",Immunome Res,,,False
741878140cd73151d5bcb9d8a951b286434f148e,PMC,An ontology for immune epitopes: application to the design of a broad scope database of immune reactivities,http://dx.doi.org/10.1186/1745-7580-1-2,PMC1287064,16305755,CC BY,"BACKGROUND: Epitopes can be defined as the molecular structures bound by specific receptors, which are recognized during immune responses. The Immune Epitope Database and Analysis Resource (IEDB) project will catalog and organize information regarding antibody and T cell epitopes from infectious pathogens, experimental antigens and self-antigens, with a priority on NIAID Category A-C pathogens () and emerging/re-emerging infectious diseases. Both intrinsic structural and phylogenetic features, as well as information relating to the interactions of the epitopes with the host's immune system will be catalogued. DESCRIPTION: To effectively represent and communicate the information related to immune epitopes, a formal ontology was developed. The semantics of the epitope domain and related concepts were captured as a hierarchy of classes, which represent the general and specialized relationships between the various concepts. A complete listing of classes and their properties can be found at . CONCLUSION: The IEDB's ontology is the first ontology specifically designed to capture both intrinsic chemical and biochemical information relating to immune epitopes with information relating to the interaction of these structures with molecules derived from the host immune system. We anticipate that the development of this type of ontology and associated databases will facilitate rigorous description of data related to immune epitopes, and might ultimately lead to completely new methods for describing and modeling immune responses.",2005 Sep 20,"['Sathiamurthy, Muthuraman', 'Peters, Bjoern', 'Bui, Huynh-Hoa', 'Sidney, John', 'Mokili, John', 'Wilson, Stephen S', 'Fleri, Ward', 'McGuinness, Deborah L', 'Bourne, Philip E', 'Sette, Alessandro']",Immunome Res,,,False
c457f06e9474f83c6451e8740c24aebe35428408,PMC,Limits to Forecasting Precision for Outbreaks of Directly Transmitted Diseases,http://dx.doi.org/10.1371/journal.pmed.0030003,PMC1288026,16435887,CC BY,"BACKGROUND: Early warning systems for outbreaks of infectious diseases are an important application of the ecological theory of epidemics. A key variable predicted by early warning systems is the final outbreak size. However, for directly transmitted diseases, the stochastic contact process by which outbreaks develop entails fundamental limits to the precision with which the final size can be predicted. METHODS AND FINDINGS: I studied how the expected final outbreak size and the coefficient of variation in the final size of outbreaks scale with control effectiveness and the rate of infectious contacts in the simple stochastic epidemic. As examples, I parameterized this model with data on observed ranges for the basic reproductive ratio (R (0)) of nine directly transmitted diseases. I also present results from a new model, the simple stochastic epidemic with delayed-onset intervention, in which an initially supercritical outbreak (R (0) > 1) is brought under control after a delay. CONCLUSION: The coefficient of variation of final outbreak size in the subcritical case (R (0) < 1) will be greater than one for any outbreak in which the removal rate is less than approximately 2.41 times the rate of infectious contacts, implying that for many transmissible diseases precise forecasts of the final outbreak size will be unattainable. In the delayed-onset model, the coefficient of variation (CV) was generally large (CV > 1) and increased with the delay between the start of the epidemic and intervention, and with the average outbreak size. These results suggest that early warning systems for infectious diseases should not focus exclusively on predicting outbreak size but should consider other characteristics of outbreaks such as the timing of disease emergence.",2006 Jan 22,"Drake, John M",PLoS Med,,,True
74d006de3306bae5ae3710903fe05d743b6531f7,PMC,Limits to Forecasting Precision for Outbreaks of Directly Transmitted Diseases,http://dx.doi.org/10.1371/journal.pmed.0030003,PMC1288026,16435887,CC BY,"BACKGROUND: Early warning systems for outbreaks of infectious diseases are an important application of the ecological theory of epidemics. A key variable predicted by early warning systems is the final outbreak size. However, for directly transmitted diseases, the stochastic contact process by which outbreaks develop entails fundamental limits to the precision with which the final size can be predicted. METHODS AND FINDINGS: I studied how the expected final outbreak size and the coefficient of variation in the final size of outbreaks scale with control effectiveness and the rate of infectious contacts in the simple stochastic epidemic. As examples, I parameterized this model with data on observed ranges for the basic reproductive ratio (R (0)) of nine directly transmitted diseases. I also present results from a new model, the simple stochastic epidemic with delayed-onset intervention, in which an initially supercritical outbreak (R (0) > 1) is brought under control after a delay. CONCLUSION: The coefficient of variation of final outbreak size in the subcritical case (R (0) < 1) will be greater than one for any outbreak in which the removal rate is less than approximately 2.41 times the rate of infectious contacts, implying that for many transmissible diseases precise forecasts of the final outbreak size will be unattainable. In the delayed-onset model, the coefficient of variation (CV) was generally large (CV > 1) and increased with the delay between the start of the epidemic and intervention, and with the average outbreak size. These results suggest that early warning systems for infectious diseases should not focus exclusively on predicting outbreak size but should consider other characteristics of outbreaks such as the timing of disease emergence.",2006 Jan 22,"Drake, John M",PLoS Med,,,False
beb3c13102cceb2b4cb9345fed015c83a8b921ed,PMC,Limits to Forecasting Precision for Outbreaks of Directly Transmitted Diseases,http://dx.doi.org/10.1371/journal.pmed.0030003,PMC1288026,16435887,CC BY,"BACKGROUND: Early warning systems for outbreaks of infectious diseases are an important application of the ecological theory of epidemics. A key variable predicted by early warning systems is the final outbreak size. However, for directly transmitted diseases, the stochastic contact process by which outbreaks develop entails fundamental limits to the precision with which the final size can be predicted. METHODS AND FINDINGS: I studied how the expected final outbreak size and the coefficient of variation in the final size of outbreaks scale with control effectiveness and the rate of infectious contacts in the simple stochastic epidemic. As examples, I parameterized this model with data on observed ranges for the basic reproductive ratio (R (0)) of nine directly transmitted diseases. I also present results from a new model, the simple stochastic epidemic with delayed-onset intervention, in which an initially supercritical outbreak (R (0) > 1) is brought under control after a delay. CONCLUSION: The coefficient of variation of final outbreak size in the subcritical case (R (0) < 1) will be greater than one for any outbreak in which the removal rate is less than approximately 2.41 times the rate of infectious contacts, implying that for many transmissible diseases precise forecasts of the final outbreak size will be unattainable. In the delayed-onset model, the coefficient of variation (CV) was generally large (CV > 1) and increased with the delay between the start of the epidemic and intervention, and with the average outbreak size. These results suggest that early warning systems for infectious diseases should not focus exclusively on predicting outbreak size but should consider other characteristics of outbreaks such as the timing of disease emergence.",2006 Jan 22,"Drake, John M",PLoS Med,,,False
45654599b3a90fd3ecfb03ca55dee622a7565e94,PMC,Communication of bed allocation decisions in a critical care unit and accountability for reasonableness,http://dx.doi.org/10.1186/1472-6963-5-67,PMC1298296,16259634,CC BY,"BACKGROUND: Communication may affect perceptions of fair process for intensive care unit bed allocation decisions through its impact on the publicity condition of accountability for reasonableness. METHODS: We performed a qualitative case study to describe participant perceptions of the communication of bed allocation decisions in an 18-bed university affiliated, medical-surgical critical care unit at Sunnybrook and Women's College Health Sciences Centre. Interviewed participants were 3 critical care physicians, 4 clinical fellows in critical care, 4 resource nurses, 4 ""end-users"" (physicians who commonly referred patients to the unit), and 3 members of the administrative staff. Median bed occupancy during the study period (Jan-April 2003) was 18/18; daily admissions and discharges (median) were 3. We evaluated our description using the ethical framework ""accountability for reasonableness"" (A4R) to identify opportunities for improvement. RESULTS: The critical care physician, resource nurse, critical care fellow and end-users (trauma team leader, surgeons, neurosurgeons, anesthesiologists) functioned independently in unofficial ""parallel tracks"" of bed allocation decision-making; this conflicted with the official designation of the critical care physician as the sole authority. Communication between key decision-makers was indirect and could exclude those affected by the decisions; notably, family members. Participants perceived a lack of publicity for bed allocation rationales. CONCLUSION: The publicity condition should be improved for critical care bed allocation decisions. Decision-making in the ""parallel tracks"" we describe might be unavoidable within usual constraints of time, urgency and demand. Formal guidelines for direct communication between key participants in such circumstances would help to improve the fairness of these decisions.",2005 Oct 31,"['Cooper, Andrew B', 'Joglekar, Amit S', 'Gibson, Jennifer', 'Swota, Alissa H', 'Martin, Douglas K']",BMC Health Serv Res,,,True
07fc7bb8cbdb82bd4b17681aa92a6fc06d5fcf82,PMC,Functional and Genetic Analysis of Coronavirus Replicase-Transcriptase Proteins,http://dx.doi.org/10.1371/journal.ppat.0010039,PMC1298938,16341254,CC BY,"The coronavirus replicase-transcriptase complex is an assembly of viral and cellular proteins that mediate the synthesis of genome and subgenome-sized mRNAs in the virus-infected cell. Here, we report a genetic and functional analysis of 19 temperature-sensitive (ts) mutants of Murine hepatitis virus MHV-A59 that are unable to synthesize viral RNA when the infection is initiated and maintained at the non-permissive temperature. Both classical and biochemical complementation analysis leads us to predict that the majority of MHV-A59 ORF1a replicase gene products (non-structural proteins nsp1–nsp11) form a single complementation group (cistron1) while the replicase gene products encoded in ORF1b (non-structural proteins nsp12–nsp16) are able to function in trans and comprise at least three, and possibly five, further complementation groups (cistrons II–VI). Also, we have identified mutations in the non-structural proteins nsp 4, nsp5, nsp10, nsp12, nsp14, and nsp16 that are responsible for the ts phenotype of eight MHV-A59 mutants, which allows us to conclude that these proteins are essential for the assembly of a functional replicase-transcriptase complex. Finally, our analysis of viral RNA synthesis in ts mutant virus-infected cells allows us to discriminate three phenotypes with regard to the inability of specific mutants to synthesize viral RNA at the non-permissive temperature. Mutant LA ts6 appeared to be defective in continuing negative-strand synthesis, mutant Alb ts16 appeared to form negative strands but these were not utilized for positive-strand RNA synthesis, and mutant Alb ts22 was defective in the elongation of both positive- and negative-strand RNA. On the basis of these results, we propose a model that describes a pathway for viral RNA synthesis in MHV-A59-infected cells. Further biochemical analysis of these mutants should allow us to identify intermediates in this pathway and elucidate the precise function(s) of the viral replicase proteins involved.",2005 Dec 9,"['Sawicki, Stanley G', 'Sawicki, Dorothea L', 'Younker, Diane', 'Meyer, Yvonne', 'Thiel, Volker', 'Stokes, Helen', 'Siddell, Stuart G']",PLoS Pathog,,,True
56bea8bc53d2703d7d33244508932aa26d1ad442,PMC,RNA Viral Community in Human Feces: Prevalence of Plant Pathogenic Viruses,http://dx.doi.org/10.1371/journal.pbio.0040003,PMC1310650,16336043,CC BY,"The human gut is known to be a reservoir of a wide variety of microbes, including viruses. Many RNA viruses are known to be associated with gastroenteritis; however, the enteric RNA viral community present in healthy humans has not been described. Here, we present a comparative metagenomic analysis of the RNA viruses found in three fecal samples from two healthy human individuals. For this study, uncultured viruses were concentrated by tangential flow filtration, and viral RNA was extracted and cloned into shotgun viral cDNA libraries for sequencing analysis. The vast majority of the 36,769 viral sequences obtained were similar to plant pathogenic RNA viruses. The most abundant fecal virus in this study was pepper mild mottle virus (PMMV), which was found in high concentrations—up to 10(9) virions per gram of dry weight fecal matter. PMMV was also detected in 12 (66.7%) of 18 fecal samples collected from healthy individuals on two continents, indicating that this plant virus is prevalent in the human population. A number of pepper-based foods tested positive for PMMV, suggesting dietary origins for this virus. Intriguingly, the fecal PMMV was infectious to host plants, suggesting that humans might act as a vehicle for the dissemination of certain plant viruses.",2006 Jan 20,"['Zhang, Tao', 'Breitbart, Mya', 'Lee, Wah Heng', 'Run, Jin-Quan', 'Wei, Chia Lin', 'Soh, Shirlena Wee Ling', 'Hibberd, Martin L', 'Liu, Edison T', 'Rohwer, Forest', 'Ruan, Yijun']",PLoS Biol,,,True
0a1533470817bc5ef0d0d0af56386a96b505dc0d,PMC,Evaluation of potential reference genes in real-time RT-PCR studies of Atlantic salmon,http://dx.doi.org/10.1186/1471-2199-6-21,PMC1314898,16293192,CC BY,"BACKGROUND: Salmonid fishes are among the most widely studied model fish species but reports on systematic evaluation of reference genes in qRT-PCR studies is lacking. RESULTS: The stability of six potential reference genes was examined in eight tissues of Atlantic salmon (Salmo salar), to determine the most suitable genes to be used in quantitative real-time RT-PCR analyses. The relative transcription levels of genes encoding 18S rRNA, S20 ribosomal protein, β-actin, glyceraldehyde-3P-dehydrogenase (GAPDH), and two paralog genes encoding elongation factor 1A (EF1A(A )and EF1A(B)) were quantified in gills, liver, head kidney, spleen, thymus, brain, muscle, and posterior intestine in six untreated adult fish, in addition to a group of individuals that went through smoltification. Based on calculations performed with the geNorm VBA applet, which determines the most stable genes from a set of tested genes in a given cDNA sample, the ranking of the examined genes in adult Atlantic salmon was EF1A(B)>EF1A(A)>β-actin>18S rRNA>S20>GAPDH. When the same calculations were done on a total of 24 individuals from four stages in the smoltification process (presmolt, smolt, smoltified seawater and desmoltified freshwater), the gene ranking was EF1A(B)>EF1A(A)>S20>β-actin>18S rRNA>GAPDH. CONCLUSION: Overall, this work suggests that the EF1A(A )and EF1A(B )genes can be useful as reference genes in qRT-PCR examination of gene expression in the Atlantic salmon.",2005 Nov 17,"['Olsvik, Pål A', 'Lie, Kai K', 'Jordal, Ann-Elise O', 'Nilsen, Tom O', 'Hordvik, Ivar']",BMC Mol Biol,,,True
86adefc2b5acac8a4ca321db6db5ec03408f07bd,PMC,Ecological Change: Life Lessons,,PMC1314962,,CC0,,2005 Dec,"Bonn, Dorothy",Environ Health Perspect,,,True
2739ea989ec040104223cfb49d2a13d7d89dc79a,PMC,Selection of reference genes for quantitative real-time PCR in bovine preimplantation embryos,http://dx.doi.org/10.1186/1471-213X-5-27,PMC1315359,16324220,CC BY,"BACKGROUND: Real-time quantitative PCR is a sensitive and very efficient technique to examine gene transcription patterns in preimplantation embryos, in order to gain information about embryo development and to optimize assisted reproductive technologies. Critical to the succesful application of real-time PCR is careful assay design, reaction optimization and validation to maximize sensitivity and accuracy. In most of the studies published GAPD, ACTB or 18S rRNA have been used as a single reference gene without prior verification of their expression stability. Normalization of the data using unstable controls can result in erroneous conclusions, especially when only one reference gene is used. RESULTS: In this study the transcription levels of 8 commonly used reference genes (ACTB, GAPD, Histone H2A, TBP, HPRT1, SDHA, YWHAZ and 18S rRNA) were determined at different preimplantation stages (2-cell, 8-cell, blastocyst and hatched blastocyst) in order to select the most stable genes to normalize quantitative data within different preimplantation embryo stages. CONCLUSION: Using the geNorm application YWHAZ, GAPD and SDHA were found to be the most stable genes across the examined embryonic stages, while the commonly used ACTB was shown to be highly regulated. We recommend the use of the geometric mean of those 3 reference genes as an accurate normalization factor, which allows small expression differences to be reliably measured.",2005 Dec 3,"['Goossens, Karen', 'Van Poucke, Mario', 'Van Soom, Ann', 'Vandesompele, Jo', 'Van Zeveren, Alex', 'Peelman, Luc J']",BMC Dev Biol,,,True
c82d59add457527b2858fb5157a92634815d9387,PMC,The New International Health Regulations and the Federalism Dilemma,http://dx.doi.org/10.1371/journal.pmed.0030001,PMC1315361,16354103,CC BY,"The recent revision of the International Health Regulations, say Wilson and colleagues, is both long overdue and eminently necessary to face the challenges of an increasingly globalized world.",2006 Jan 20,"['Wilson, Kumanan', 'McDougall, Christopher', 'Upshur, Ross']",PLoS Med,,,True
e97ccc39b73b40f090df148361e6326f0a5798b6,PMC,Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells,http://dx.doi.org/10.1186/1465-9921-6-135,PMC1318487,16283933,CC BY,"BACKGROUND: Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells. METHODS: We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro. RESULTS: We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus. CONCLUSION: The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease.",2005 Nov 11,"['Chan, MCW', 'Cheung, CY', 'Chui, WH', 'Tsao, SW', 'Nicholls, JM', 'Chan, YO', 'Chan, RWY', 'Long, HT', 'Poon, LLM', 'Guan, Y', 'Peiris, JSM']",Respir Res,,,True
a5add18a3b3f98e15c3afcc6186642140033d975,PMC,Promoter Variation in the DC-SIGN–Encoding Gene CD209 Is Associated with Tuberculosis,http://dx.doi.org/10.1371/journal.pmed.0030020,PMC1324949,16379498,CC BY,"BACKGROUND: Tuberculosis, which is caused by Mycobacterium tuberculosis, remains one of the leading causes of mortality worldwide. The C-type lectin DC-SIGN is known to be the major M. tuberculosis receptor on human dendritic cells. We reasoned that if DC-SIGN interacts with M. tuberculosis, as well as with other pathogens, variation in this gene might have a broad range of influence in the pathogenesis of a number of infectious diseases, including tuberculosis. METHODS AND FINDINGS: We tested whether polymorphisms in CD209, the gene encoding DC-SIGN, are associated with susceptibility to tuberculosis through sequencing and genotyping analyses in a South African cohort. After exclusion of significant population stratification in our cohort, we observed an association between two CD209 promoter variants (−871G and −336A) and decreased risk of developing tuberculosis. By looking at the geographical distribution of these variants, we observed that their allelic combination is mainly confined to Eurasian populations. CONCLUSIONS: Our observations suggest that the two −871G and −336A variants confer protection against tuberculosis. In addition, the geographic distribution of these two alleles, together with their phylogenetic status, suggest that they may have increased in frequency in non-African populations as a result of host genetic adaptation to a longer history of exposure to tuberculosis. Further characterization of the biological consequences of DC-SIGN variation in tuberculosis will be crucial to better appreciate the role of this lectin in interactions between the host immune system and the tubercle bacillus as well as other pathogens.",2006 Feb 3,"['Barreiro, Luis B', 'Neyrolles, Olivier', 'Babb, Chantal L', 'Tailleux, Ludovic', 'Quach, Hélène', 'McElreavey, Ken', 'van Helden, Paul D.', 'Hoal, Eileen G', 'Gicquel, Brigitte', 'Quintana-Murci, Lluis']",PLoS Med,,,True
325688eb32f8e6875a930f831c4cea02b2a556c9,PMC,Time Course and Cellular Localization of SARS-CoV Nucleoprotein and RNA in Lungs from Fatal Cases of SARS,http://dx.doi.org/10.1371/journal.pmed.0030027,PMC1324951,16379499,CC BY,"BACKGROUND: Cellular localization of severe acute respiratory syndrome coronavirus (SARS-CoV) in the lungs of patients with SARS is important in confirming the etiological association of the virus with disease as well as in understanding the pathogenesis of the disease. To our knowledge, there have been no comprehensive studies investigating viral infection at the cellular level in humans. METHODS AND FINDINGS: We collected the largest series of fatal cases of SARS with autopsy material to date by merging the pathological material from two regions involved in the 2003 worldwide SARS outbreak in Hong Kong, China, and Toronto, Canada. We developed a monoclonal antibody against the SARS-CoV nucleoprotein and used it together with in situ hybridization (ISH) to analyze the autopsy lung tissues of 32 patients with SARS from Hong Kong and Toronto. We compared the results of these assays with the pulmonary pathologies and the clinical course of illness for each patient. SARS-CoV nucleoprotein and RNA were detected by immunohistochemistry and ISH, respectively, primarily in alveolar pneumocytes and, less frequently, in macrophages. Such localization was detected in four of the seven patients who died within two weeks of illness onset, and in none of the 25 patients who died later than two weeks after symptom onset. CONCLUSIONS: The pulmonary alveolar epithelium is the chief target of SARS-CoV, with macrophages infected subsequently. Viral replication appears to be limited to the first two weeks after symptom onset, with little evidence of continued widespread replication after this period. If antiviral therapy is considered for future treatment, it should be focused on this two-week period of acute clinical disease.",2006 Feb 3,"['Nicholls, John M', 'Butany, Jagdish', 'Poon, Leo L. M', 'Chan, Kwok H', 'Beh, Swan Lip', 'Poutanen, Susan', 'Peiris, J. S. Malik', 'Wong, Maria']",PLoS Med,,,True
038f6e6dbf6b5d3b0ab71e5f20dadb4cf675cd0b,PMC,Pathological Clues to How the SARS Virus Kills,http://dx.doi.org/10.1371/journal.pmed.0030059,PMC1324952,,CC BY,,2006 Feb 3,,PLoS Med,,,False
58bb44f68691a167fdfb89c3a90f8fe520e37d06,PMC,Lung Infection—A Public Health Priority,http://dx.doi.org/10.1371/journal.pmed.0030076,PMC1326257,16401173,CC BY,"The pervasive burden of lung infections receives proportionately little attention from the biomedical and public health communities, argues Mizgerd.",2006 Feb 17,"Mizgerd, Joseph P",PLoS Med,,,True
c6202f96bd4b2aea699d5fbe867f311498dca3aa,PMC,Bioethical Implications of Globalization: An International Consortium Project of the European Commission,http://dx.doi.org/10.1371/journal.pmed.0030043,PMC1351155,16420098,CC BY,The BIG project looks at some of the ethical concerns surrounding globalization and health.,2006 Feb 24,"['Novotny, Thomas E', 'Mordini, Emilio', 'Chadwick, Ruth', 'Pedersen, J. Martin', 'Fabbri, Fabrizio', 'Lie, Reidar', 'Thanachaiboot, Natapong', 'Mossialos, Elias', 'Permanand, Govin']",PLoS Med,,,True
a78fd1b34372e1e54bf2a192d04aa36670cea307,PMC,Public awareness of risk factors for cancer among the Japanese general population: A population-based survey,http://dx.doi.org/10.1186/1471-2458-6-2,PMC1351169,16403223,CC BY,"BACKGROUND: The present study aimed to provide information on awareness of the attributable fraction of cancer causes among the Japanese general population. METHODS: A nationwide representative sample of 2,000 Japanese aged 20 or older was asked about their perception and level of concern about various environmental and genetic risk factors in relation to cancer prevention, as a part of an Omnibus Survey. Interviews were conducted with 1,355 subjects (609 men and 746 women). RESULTS: Among 12 risk factor candidates, the attributable fraction of cancer-causing viral and bacterial infection was considered highest (51%), followed by that of tobacco smoking (43%), stress (39%), and endocrine-disrupting chemicals (37%). On the other hand, the attributable fractions of cancer by charred fish and meat (21%) and alcohol drinking (22%) were considered low compared with other risk factor candidates. For most risk factors, attributable fraction responses were higher in women than in men. As a whole, the subjects tended to respond with higher values than those estimated by epidemiologic evidence in the West. The attributable fraction of cancer speculated to be genetically determined was 32%, while 36% of cancer was considered preventable by improving lifestyle. CONCLUSION: Our results suggest that awareness of the attributable fraction of cancer causes in the Japanese general population tends to be dominated by cancer-causing infection, occupational exposure, air pollution and food additives rather than major lifestyle factors such as diet.",2006 Jan 10,"['Inoue, Manami', 'Iwasaki, Motoki', 'Otani, Tetsuya', 'Sasazuki, Shizuka', 'Tsugane, Shoichiro']",BMC Public Health,,,True
75025fdc2dbeab398880d6e072274409f3dc14bd,PMC,ZCURVE_V: a new self-training system for recognizing protein-coding genes in viral and phage genomes,http://dx.doi.org/10.1186/1471-2105-7-9,PMC1352377,16401352,CC BY,"BACKGROUND: It necessary to use highly accurate and statistics-based systems for viral and phage genome annotations. The GeneMark systems for gene-finding in virus and phage genomes suffer from some basic drawbacks. This paper puts forward an alternative approach for viral and phage gene-finding to improve the quality of annotations, particularly for newly sequenced genomes. RESULTS: The new system ZCURVE_V has been run for 979 viral and 212 phage genomes, respectively, and satisfactory results are obtained. To have a fair comparison with the currently available software of similar function, GeneMark, a total of 30 viral genomes that have not been annotated by GeneMark are selected to be tested. Consequently, the average specificity of both systems is well matched, however the average sensitivity of ZCURVE_V for smaller viral genomes (< 100 kb), which constitute the main parts of viral genomes sequenced so far, is higher than that of GeneMark. Additionally, for the genome of Amsacta moorei entomopoxvirus, probably with the lowest genomic GC content among the sequenced organisms, the accuracy of ZCURVE_V is much better than that of GeneMark, because the later predicts hundreds of false-positive genes. ZCURVE_V is also used to analyze well-studied genomes, such as HIV-1, HBV and SARS-CoV. Accordingly, the performance of ZCURVE_V is generally better than that of GeneMark. Finally, ZCURVE_V may be downloaded and run locally, particularly facilitating its utilization, whereas GeneMark is not downloadable. Based on the above comparison, it is suggested that ZCURVE_V may serve as a preferred gene-finding tool for viral and phage genomes newly sequenced. However, it is also shown that the joint application of both systems, ZCURVE_V and GeneMark, leads to better gene-finding results. The system ZCURVE_V is freely available at: . CONCLUSION: ZCURVE_V may serve as a preferred gene-finding tool used for viral and phage genomes, especially for anonymous viral and phage genomes newly sequenced.",2006 Jan 10,"['Guo, Feng-Biao', 'Zhang, Chun-Ting']",BMC Bioinformatics,,,True
2f9f32fc7d8af64617d6bbd88c7a42dec0e13a90,PMC,Evidence of host-virus co-evolution in tetranucleotide usage patterns of bacteriophages and eukaryotic viruses,http://dx.doi.org/10.1186/1471-2164-7-8,PMC1360066,16417644,CC BY,"BACKGROUND: Virus taxonomy is based on morphologic characteristics, as there are no widely used non-phenotypic measures for comparison among virus families. We examined whether there is phylogenetic signal in virus nucleotide usage patterns that can be used to determine ancestral relationships. The well-studied model of tail morphology in bacteriophage classification was used for comparison with nucleotide usage patterns. Tetranucleotide usage deviation (TUD) patterns were chosen since they have previously been shown to contain phylogenetic signal similar to that of 16S rRNA. RESULTS: We found that bacteriophages have unique TUD patterns, representing genomic signatures that are relatively conserved among those with similar host range. Analysis of TUD-based phylogeny indicates that host influences are important in bacteriophage evolution, and phylogenies containing both phages and their hosts support their co-evolution. TUD-based phylogeny of eukaryotic viruses indicates that they cluster largely based on nucleic acid type and genome size. Similarities between eukaryotic virus phylogenies based on TUD and gene content substantiate the TUD methodology. CONCLUSION: Differences between phenotypic and TUD analysis may provide clues to virus ancestry not previously inferred. As such, TUD analysis provides a complementary approach to morphology-based systems in analysis of virus evolution.",2006 Jan 18,"['Pride, David T', 'Wassenaar, Trudy M', 'Ghose, Chandrabali', 'Blaser, Martin J']",BMC Genomics,,,True
c6bf372c094f035a514975c35a7f9c094abbe493,PMC,Sequence specific visual detection of LAMP reactions by addition of cationic polymers,http://dx.doi.org/10.1186/1472-6750-6-3,PMC1373654,16401354,CC BY,"BACKGROUND: Development of a practical gene point-of-care testing device (g-POCT device) requires innovative detection methods for demonstrating the results of the gene amplification reaction without the use of expensive equipment. We have studied a new method for the sequence-specific visual detection of minute amounts of nucleic acids using precipitation reaction by addition of cationic polymers to amplicons of Loop mediated isothermal Amplification (LAMP). RESULTS: Oligo DNA probes labeled with different fluorescent dyes were prepared for multiple nucleic acid templates, and the templates were amplified by the LAMP reactions under the existence of the probes. At completion of the LAMP reaction, an optimal amount of low molecular weight polyethylenimine (PEI) was added, resulting in the precipitation of the insoluble LAMP amplicon-PEI complex. The fluorescently labeled Oligo DNA probes hybridized to the LAMP product were incorporated into the precipitation, and the precipitate emitted fluorescence corresponding to the amplified nucleic acid templates. The color of emitted fluorescence can be detected easily by naked eye on a conventional UV illuminator. CONCLUSION: The presence or absence of minute amount of nucleic acid templates could be detected in a simple manner through visual assessment for the color of the LAMP amplicon-PEI complex precipitate. We conclude that this detection method may facilitate development of small and simple g-POCT device.",2006 Jan 10,"['Mori, Yasuyoshi', 'Hirano, Tsuyoshi', 'Notomi, Tsugunori']",BMC Biotechnol,,,True
882b4b4a41b772d31e8f9e860882088336f26e26,PMC,Automated extraction protocol for quantification of SARS-Coronavirus RNA in serum: an evaluation study,http://dx.doi.org/10.1186/1471-2334-6-20,PMC1382231,16466582,CC BY,"BACKGROUND: We have previously developed a test for the diagnosis and prognostic assessment of the severe acute respiratory syndrome (SARS) based on the detection of the SARS-coronavirus RNA in serum by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). In this study, we evaluated the feasibility of automating the serum RNA extraction procedure in order to increase the throughput of the assay. METHODS: An automated nucleic acid extraction platform using the MagNA Pure LC instrument (Roche Diagnostics) was evaluated. We developed a modified protocol in compliance with the recommended biosafety guidelines from the World Health Organization based on the use of the MagNA Pure total nucleic acid large volume isolation kit for the extraction of SARS-coronavirus RNA. The modified protocol was compared with a column-based extraction kit (QIAamp viral RNA mini kit, Qiagen) for quantitative performance, analytical sensitivity and precision. RESULTS: The newly developed automated protocol was shown to be free from carry-over contamination and have comparable performance with other standard protocols and kits designed for the MagNA Pure LC instrument. However, the automated method was found to be less sensitive, less precise and led to consistently lower serum SARS-coronavirus concentrations when compared with the column-based extraction method. CONCLUSION: As the diagnostic efficiency and prognostic value of the serum SARS-CoV RNA RT-PCR test is critically associated with the analytical sensitivity and quantitative performance contributed both by the RNA extraction and RT-PCR components of the test, we recommend the use of the column-based manual RNA extraction method.",2006 Feb 9,"['Chiu, Rossa WK', 'Jin, Yongjie', 'Chung, Grace TY', 'Lui, Wing-bong', 'Chan, Anthony TC', 'Lim, Wilina', 'Dennis Lo, YM']",BMC Infect Dis,,,True
abb703e29b1ee7ddf60006b33de199828666d7b1,PMC,The Scientific Response to a Pandemic,http://dx.doi.org/10.1371/journal.ppat.0020009,PMC1383484,16738708,CC BY,,2006 Feb 24,"['Gronvall, Gigi Kwik', 'Waldhorn, Richard E', 'Henderson, D. A']",PLoS Pathog,,,True
c9eb97be96131dee33d53b03c46dacecf63c02b1,PMC,Correction: Functional and Genetic Analysis of Coronavirus Replicase-Transcriptase Proteins,http://dx.doi.org/10.1371/journal.ppat.0020017,PMC1383490,,CC BY,,2006 Feb 24,"['Sawicki, Stanley G', 'Sawicki, Dorothea L', 'Younker, Diane', 'Meyer, Yvonne', 'Thiel, Volker', 'Stokes, Helen', 'Siddell, Stuart G']",PLoS Pathog,,,True
66a1d5898c1fb5c8e8554f92e446d262abb10fdb,PMC,Correlation between the presence of neutralizing antibodies against porcine circovirus 2 (PCV2) and protection against replication of the virus and development of PCV2-associated disease,http://dx.doi.org/10.1186/1746-6148-2-6,PMC1386657,16445856,CC BY,"BACKGROUND: In a previous study, it was demonstrated that high replication of Porcine circovirus 2 (PCV2) in a gnotobiotic pig was correlated with the absence of PCV2-neutralizing antibodies. The aim of the present study was to investigate if this correlation could also be found in SPF pigs in which PMWS was experimentally reproduced and in naturally PMWS-affected pigs. RESULTS: When looking at the total anti-PCV2 antibody titres, PMWS-affected and healthy animals seroconverted at the same time point, and titres in PMWS-affected animals were only slightly lower compared to those in healthy animals. In healthy animals, the evolution of PCV2-neutralizing antibodies coincided with that of total antibodies. In PMWS-affected animals, neutralizing antibodies could either not be found (sera from field studies) or were detected in low titres between 7 and 14 DPI only (sera from experimentally inoculated SPF pigs). Differences were also found in the evolution of specific antibody isotypes titres against PCV2. In healthy pigs, IgM antibodies persisted until the end of the study, whereas in PMWS-affected pigs they quickly decreased or remained present at low titres. The mean titres of other antibody isotypes (IgG1, IgG2 and IgA), were slightly lower in PMWS-affected pigs compared to their healthy group mates at the end of each study. CONCLUSION: This study describes important differences in the development of the humoral immune response between pigs that get subclinically infected with PCV2 and pigs that experience a high level of PCV2-replication which in 3 of 4 experiments led to the development of PMWS. These observations may contribute to a better understanding of the pathogenesis of a PCV2-infection.",2006 Jan 30,"['Meerts, Peter', 'Misinzo, Gerald', 'Lefebvre, David', 'Nielsen, Jens', 'Bøtner, Anette', 'Kristensen, Charlotte S', 'Nauwynck, Hans J']",BMC Vet Res,,,True
f50562c5a5e9f206dba3c559e6b4f5b65aadf7f4,PMC,Epstein-barr virus induced cellular changes in nasal mucosa,http://dx.doi.org/10.1186/1743-422X-3-6,PMC1388193,16451721,CC BY,"A 21-year-old man presented with nasal obstruction of the right nasal fossa of 1 year duration. Nasal endoscopy revealed in the right inferior turbinate head a rounded neoplasm about 1 cm in diameter. Cytologic study of a nasal scraping specimen disclosed numerous clusters containing columnar cells with cytomegaly, prominent multinucleation, markedly sparse shortened cilia; the cytoplasm contained an acidophil area and a small round area that stained poorly; cells with a large intracytoplasmic vacuole that was acidophil and PAS+. Serology tests using the nested polymer chain reaction (PCR) technique on serum, nasal and pharyngeal smears revealed an Epstein-Barr virus (EBV) infection that was confirmed at electron microscopy. The clinical and cytological features resolved 19 months after the initial evaluation. CONCLUSION: The authors advise carrying out clinical (endoscopy, serology, etc.) evaluation of all endonasal neoplasms and to routinely perform cytological study on nasal scraping specimens. When samples test positive for EBV, nasal and nasopharyngeal endoscopy should be performed regularly to detect possible evidence for nasopharyngeal carcinoma (NPC).",2006 Feb 1,"['Gelardi, Matteo', 'Tomaiuolo, Marilena', 'Cassano, Michele', 'Besozzi, Gaspare', 'Fiorella, Maria Luisa', 'Calvario, Agata', 'Castellano, Maria Antonia', 'Cassano, Pasquale']",Virol J,,,True
f50b6632623eb4fe2193588b4f2c217c7125872d,PMC,Virus-mediated autoimmunity in Multiple Sclerosis,http://dx.doi.org/10.1186/1740-2557-3-1,PMC1397830,16504001,CC BY,"Epidemiological data suggest the notion that in Multiple Sclerosis (MS) is an acquired autoimmune disease and the cause may be an environmental factor(s), probably infectious, in genetically susceptible individuals. Several cases of viral induced demyelinatimg encephalomyelitis in human beings and in experimental models as well as the presence of IgG oligoclonal bands in the cerebrospinal fluid indicate that the infectious factor may be viral. However, the absence of a specific virus identification in MS central nervous system may hardly support this notion. On the other hand, the partial response of patients with MS to immunosuppressive and immunomodulatory therapy support the evidence of an autoimmune etiology for MS. However, the autoimmune hypothesis shares the same criticism with the infectious one in that no autoantigen(s) specific to and causative for MS has ever been identified. Nevertheless, the absence of identifiable infectious agent, especially viral does not rule out its presence at a certain time – point and the concomitant long term triggering of an autoimmune cascade of events thereafter. Several concepts have emerged in an attempt to explain the autoimmune mechanisms and ongoing neurodegeneration in MS on the basis of the infectious – viral hypothesis.",2006 Feb 19,"['Grigoriadis, Nikolaos', 'Hadjigeorgiou, Georgios M']",J Autoimmune Dis,,,True
5f50a65482a507e61c9a7cd9a9b80a0017494dcb,PMC,"Globalization, migration health, and educational preparation for transnational medical encounters",http://dx.doi.org/10.1186/1744-8603-2-2,PMC1403753,16441899,CC BY,"Unprecedented migration, a core dimension of contemporary globalization, challenges population health. In a world of increasing human mobility, many health outcomes are shaped by transnational interactions among care providers and care recipients who meet in settings where nationality/ethnic match is not an option. This review article explores the value of transnational competence (TC) education as preparation for ethnically and socially discordant clinical encounters. The relevance of TC's five core skill domains (analytic, emotional, creative, communicative, and functional) for migration health and the medical-school curriculum is elaborated. A pedagogical approach that prepares for the transnational health-care consultation is presented, with a focus on clinical-clerkship learning experiences. Educational preparation for contemporary medical encounters needs to include a comprehensive set of patient-focused interpersonal skills, be adaptable to a wide variety of service users and global practice sites, and possess utility in addressing both the quality of patient care and socio-political constraints on migration health.",2006 Jan 30,"Koehn, Peter H",Global Health,,,True
dff11250a455815390e0d3c8a6208f608aa681ec,PMC,Developing nucleic acid-based electrical detection systems,http://dx.doi.org/10.1186/1475-2859-5-9,PMC1420323,16512917,CC BY,"Development of nucleic acid-based detection systems is the main focus of many research groups and high technology companies. The enormous work done in this field is particularly due to the broad versatility and variety of these sensing devices. From optical to electrical systems, from label-dependent to label-free approaches, from single to multi-analyte and array formats, this wide range of possibilities makes the research field very diversified and competitive. New challenges and requirements for an ideal detector suitable for nucleic acid analysis include high sensitivity and high specificity protocol that can be completed in a relatively short time offering at the same time low detection limit. Moreover, systems that can be miniaturized and automated present a significant advantage over conventional technology, especially if detection is needed in the field. Electrical system technology for nucleic acid-based detection is an enabling mode for making miniaturized to micro- and nanometer scale bio-monitoring devices via the fusion of modern micro- and nanofabrication technology and molecular biotechnology. The electrical biosensors that rely on the conversion of the Watson-Crick base-pair recognition event into a useful electrical signal are advancing rapidly, and recently are receiving much attention as a valuable tool for microbial pathogen detection. Pathogens may pose a serious threat to humans, animal and plants, thus their detection and analysis is a significant element of public health. Although different conventional methods for detection of pathogenic microorganisms and their toxins exist and are currently being applied, improvements of molecular-based detection methodologies have changed these traditional detection techniques and introduced a new era of rapid, miniaturized and automated electrical chip detection technologies into pathogen identification sector. In this review some developments and current directions in nucleic acid-based electrical detection are discussed.",2006 Mar 2,"Gabig-Ciminska, Magdalena",Microb Cell Fact,,,True
dca1ffcfcd6a2b7c8495e77c438d6b91d065bbf5,PMC,Specific detection of H5N1 avian influenza A virus in field specimens by a one-step RT-PCR assay,http://dx.doi.org/10.1186/1471-2334-6-40,PMC1421410,16512903,CC BY,"BACKGROUND: Continuous outbreaks of the highly pathogenic H5N1 avian influenza A in Asia has resulted in an urgent effort to improve current diagnostics to aid containment of the virus and lower the threat of a influenza pandemic. We report here the development of a PCR-based assay that is highly specific for the H5N1 avian influenza A virus. METHODS: A one-step reverse-transcription PCR assay was developed to detect the H5N1 avian influenza A virus. The specificity of the assay was shown by testing sub-types of influenza A virus and other viral and bacterial pathogens; and on field samples. RESULTS: Validation on 145 field specimens from Vietnam and Malaysia showed that the assay was specific without cross reactivity to a number of other infuenza strains as well as human respiratory related pathogens. Detection was 100% from allantoic fluid in H5N1 positive samples, suggesting it to be a reliable sampling source for accurate detection. CONCLUSION: The assay developed from this study indicates that the primers are specific for the H5N1 influenza virus. As shown by the field tested results, this assay would be highly useful as a diagnostic tool to help identify and control influenza epidemics.",2006 Mar 2,"['Ng, Lisa FP', 'Barr, Ian', 'Nguyen, Tung', 'Noor, Suriani Mohd', 'Tan, Rosemary Sok-Pin', 'Agathe, Lora V', 'Gupta, Sanjay', 'Khalil, Hassuzana', 'To, Thanh Long', 'Hassan, Sharifah Syed', 'Ren, Ee-Chee']",BMC Infect Dis,,,True
5b8bd7273e2cd3875283e705102b12ddf38d25c8,PMC,"Using Ontario's ""Telehealth"" health telephone helpline as an early-warning system: a study protocol",http://dx.doi.org/10.1186/1472-6963-6-10,PMC1431529,16480500,CC BY,"BACKGROUND: The science of syndromic surveillance is still very much in its infancy. While a number of syndromic surveillance systems are being evaluated in the US, very few have had success thus far in predicting an infectious disease event. Furthermore, to date, the majority of syndromic surveillance systems have been based primarily in emergency department settings, with varying levels of enhancement from other data sources. While research has been done on the value of telephone helplines on health care use and patient satisfaction, very few projects have looked at using a telephone helpline as a source of data for syndromic surveillance, and none have been attempted in Canada. The notable exception to this statement has been in the UK where research using the national NHS Direct system as a syndromic surveillance tool has been conducted. METHODS/DESIGN: The purpose of our proposed study is to evaluate the effectiveness of Ontario's telephone nursing helpline system as a real-time syndromic surveillance system, and how its implementation, if successful, would have an impact on outbreak event detection in Ontario. Using data collected retrospectively, all ""reasons for call"" and assigned algorithms will be linked to a syndrome category. Using different analytic methods, normal thresholds for the different syndromes will be ascertained. This will allow for the evaluation of the system's sensitivity, specificity and positive predictive value. The next step will include the prospective monitoring of syndromic activity, both temporally and spatially. DISCUSSION: As this is a study protocol, there are currently no results to report. However, this study has been granted ethical approval, and is now being implemented. It is our hope that this syndromic surveillance system will display high sensitivity and specificity in detecting true outbreaks within Ontario, before they are detected by conventional surveillance systems. Future results will be published in peer-reviewed journals so as to contribute to the growing body of evidence on syndromic surveillance, while also providing an non US-centric perspective.",2006 Feb 15,"['Rolland, Elizabeth', 'Moore, Kieran M', 'Robinson, Victoria A', 'McGuinness, Don']",BMC Health Serv Res,,,True
5208ab18e0b8b851eabda0c5c83c1d31156da8e0,PMC,Evolution of the uniquely adaptable lentiviral envelope in a natural reservoir host,http://dx.doi.org/10.1186/1742-4690-3-19,PMC1431560,16549011,CC BY,"BACKGROUND: The ability of emerging pathogens to infect new species is likely related to the diversity of pathogen variants present in existing reservoirs and their degree of genomic plasticity, which determines their ability to adapt to new environments. Certain simian immunodeficiency viruses (SIVcpz, SIVsm) have demonstrated tremendous success in infecting new species, including humans, resulting in the HIV-1 and HIV-2 epidemics. Although SIV diversification has been studied on a population level, the essential substrates for cross-species transmission, namely SIV sequence diversity and the types and extent of viral diversification present in individual reservoir animals have not been elucidated. To characterize this intra-host SIV diversity, we performed sequence analyses of clonal viral envelope (env) V1V2 and gag p27 variants present in individual SIVsm-infected sooty mangabeys over time. RESULTS: SIVsm demonstrated extensive intra-animal V1V2 length variation and amino acid diversity (le38%), and continual variation in V1V2 N-linked glycosylation consensus sequence frequency and location. Positive selection was the predominant evolutionary force. Temporal sequence shifts suggested continual selection, likely due to evolving antibody responses. In contrast, gag p27 was predominantly under purifying selection. SIVsm V1V2 sequence diversification is at least as great as that in HIV-1 infected humans, indicating that extensive viral diversification in and of itself does not inevitably lead to AIDS. CONCLUSION: Positive diversifying selection in this natural reservoir host is the engine that has driven the evolution of the uniquely adaptable SIV/HIV envelope protein. These studies emphasize the importance of retroviral diversification within individual host reservoir animals as a critical substrate in facilitating cross-species transmission.",2006 Mar 20,"['Demma, LJ', 'Vanderford, TH', 'Logsdon, JM', 'Feinberg, MB', 'Staprans, SI']",Retrovirology,,,True
e7df6e6b00213948f60923cd0c111d58ffdfda00,PMC,Nonhuman Primate Models for SARS,http://dx.doi.org/10.1371/journal.pmed.0030194,PMC1435785,16608385,CC BY,Osterhaus and Haagmans discuss a new study in PLoS Medicine that supports the use of the cynomolgus macaque model to study SARS pathogenesis and to test intervention strategies.,2006 May 18,"['Haagmans, Bart L', 'Osterhaus, Albert D. M. E']",PLoS Med,,,True
c56ffdaf1cfbae5a6ed0abea495eaf7fa1cbc031,PMC,Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome,http://dx.doi.org/10.1371/journal.pmed.0030149,PMC1435788,16605302,CC0,"BACKGROUND: The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV. METHODS AND FINDINGS: In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain. CONCLUSIONS: SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.",2006 May 18,"['Lawler, James V', 'Endy, Timothy P', 'Hensley, Lisa E', 'Garrison, Aura', 'Fritz, Elizabeth A', 'Lesar, May', 'Baric, Ralph S', 'Kulesh, David A', 'Norwood, David A', 'Wasieloski, Leonard P', 'Ulrich, Melanie P', 'Slezak, Tom R', 'Vitalis, Elizabeth', 'Huggins, John W', 'Jahrling, Peter B', 'Paragas, Jason']",PLoS Med,,,True
4fc15d2af497369e0e7aa99dc78a403bdfa4790f,PMC,A Macaque Model of SARS,http://dx.doi.org/10.1371/journal.pmed.0030222,PMC1435789,,CC BY,,2006 May 18,,PLoS Med,,,True
51dd595e1404da9a49935f1df61c163b6ad01a58,PMC,Prions Adhere to Soil Minerals and Remain Infectious,http://dx.doi.org/10.1371/journal.ppat.0020032,PMC1435987,16617377,CC BY,"An unidentified environmental reservoir of infectivity contributes to the natural transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) in sheep, deer, and elk. Prion infectivity may enter soil environments via shedding from diseased animals and decomposition of infected carcasses. Burial of TSE-infected cattle, sheep, and deer as a means of disposal has resulted in unintentional introduction of prions into subsurface environments. We examined the potential for soil to serve as a TSE reservoir by studying the interaction of the disease-associated prion protein (PrP(Sc)) with common soil minerals. In this study, we demonstrated substantial PrP(Sc) adsorption to two clay minerals, quartz, and four whole soil samples. We quantified the PrP(Sc)-binding capacities of each mineral. Furthermore, we observed that PrP(Sc) desorbed from montmorillonite clay was cleaved at an N-terminal site and the interaction between PrP(Sc) and Mte was strong, making desorption of the protein difficult. Despite cleavage and avid binding, PrP(Sc) bound to Mte remained infectious. Results from our study suggest that PrP(Sc) released into soil environments may be preserved in a bioavailable form, perpetuating prion disease epizootics and exposing other species to the infectious agent.",2006 Apr 14,"['Johnson, Christopher J', 'Phillips, Kristen E', 'Schramm, Peter T', 'McKenzie, Debbie', 'Aiken, Judd M', 'Pedersen, Joel A']",PLoS Pathog,,,True
009eaad22ad509c7286b0aaa59b0751405b39d3a,PMC,Prions Adhere to Soil Minerals and Remain Infectious,http://dx.doi.org/10.1371/journal.ppat.0020032,PMC1435987,16617377,CC BY,"An unidentified environmental reservoir of infectivity contributes to the natural transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) in sheep, deer, and elk. Prion infectivity may enter soil environments via shedding from diseased animals and decomposition of infected carcasses. Burial of TSE-infected cattle, sheep, and deer as a means of disposal has resulted in unintentional introduction of prions into subsurface environments. We examined the potential for soil to serve as a TSE reservoir by studying the interaction of the disease-associated prion protein (PrP(Sc)) with common soil minerals. In this study, we demonstrated substantial PrP(Sc) adsorption to two clay minerals, quartz, and four whole soil samples. We quantified the PrP(Sc)-binding capacities of each mineral. Furthermore, we observed that PrP(Sc) desorbed from montmorillonite clay was cleaved at an N-terminal site and the interaction between PrP(Sc) and Mte was strong, making desorption of the protein difficult. Despite cleavage and avid binding, PrP(Sc) bound to Mte remained infectious. Results from our study suggest that PrP(Sc) released into soil environments may be preserved in a bioavailable form, perpetuating prion disease epizootics and exposing other species to the infectious agent.",2006 Apr 14,"['Johnson, Christopher J', 'Phillips, Kristen E', 'Schramm, Peter T', 'McKenzie, Debbie', 'Aiken, Judd M', 'Pedersen, Joel A']",PLoS Pathog,,,False
4fa871503ddbbaaead7a34fce89298a36648f662,PMC,Inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with SARS coronavirus,http://dx.doi.org/10.1186/1743-422X-3-17,PMC1444920,16571117,CC BY,"BACKGROUND: SARS coronavirus (SARS-CoV) is the etiologic agent of the severe acute respiratory syndrome. SARS-CoV mainly infects tissues of non-lymphatic origin, and the cytokine profile of those cells can determine the course of disease. Here, we investigated the cytokine response of two human non-lymphatic cell lines, Caco-2 and HEK 293, which are fully permissive for SARS-CoV. RESULTS: A comparison with established cytokine-inducing viruses revealed that SARS-CoV only weakly triggered a cytokine response. In particular, SARS-CoV did not activate significant transcription of the interferons IFN-α, IFN-β, IFN-λ1, IFN-λ2/3, as well as of the interferon-induced antiviral genes ISG56 and MxA, the chemokine RANTES and the interleukine IL-6. Interestingly, however, SARS-CoV strongly induced the chemokines IP-10 and IL-8 in the colon carcinoma cell line Caco-2, but not in the embryonic kidney cell line 293. CONCLUSION: Our data indicate that SARS-CoV suppresses the antiviral cytokine system of non-immune cells to a large extent, thus buying time for dissemination in the host. However, synthesis of IP-10 and IL-8, which are established markers for acute-stage SARS, escapes the virus-induced silencing at least in some cell types. Therefore, the progressive infiltration of immune cells into the infected lungs observed in SARS patients could be due to the production of these chemokines by the infected tissue cells.",2006 Mar 29,"['Spiegel, Martin', 'Weber, Friedemann']",Virol J,,,True
acb6848d159dbf4970d1f76474a634110b3558e7,PMC,Heterologous expression of Brucella abortus GroEL heat-shock protein in Lactococcus lactis,http://dx.doi.org/10.1186/1475-2859-5-14,PMC1444932,16556312,CC BY,"BACKGROUND: Brucella abortus is a facultative intracellular pathogen that mainly infects cattle and humans. Current vaccines rely on live attenuated strains of B. abortus, which can revert to their pathogenic status and thus are not totally safe for use in humans. Therefore, the development of mucosal live vaccines using the food-grade lactic acid bacterium, Lactococcus lactis, as an antigen delivery vector, is an attractive alternative and a safer vaccination strategy against B. abortus. Here, we report the construction of L. lactis strains genetically modified to produce B. abortus GroEL heat-shock protein, a candidate antigen, in two cellular locations, intracellular or secreted. RESULTS: Only the secreted form of GroEL was stably produced in L. lactis, suggesting a detrimental effect of GroEL protein when intracellularly produced in this bacterium. Only trace amounts of mature GroEL were detected in the supernatant fraction of induced lactococcal cultures, and the GroEL precursor remained stacked in the cell fraction. Attempts to raise the secretion yields were made, but even when GroEL was fused to a synthetic propeptide, secretion of this antigen was not improved. CONCLUSION: We found that L. lactis is able to produce, and to secrete, a stable form of GroEL into the extracellular medium. Despite the low secretion efficiency of GroEL, which suggest that this antigen interacts with the cell envelope of L. lactis, secretion seems to be the best way to achieve both production and protein yields, regardless of cellular location. The L. lactis strain secreting GroEL has potential for in vivo immunization.",2006 Mar 23,"['Miyoshi, Anderson', 'Bermúdez-Humarán, Luis G', 'Ribeiro, Luciana A', 'Le Loir, Yves', 'Oliveira, Sérgio C', 'Langella, Philippe', 'Azevedo, Vasco']",Microb Cell Fact,,,True
4691c6219bc10483f3291813a98d4145c1876827,PMC,Delaying the International Spread of Pandemic Influenza,http://dx.doi.org/10.1371/journal.pmed.0030212,PMC1450020,16640458,CC BY,"BACKGROUND: The recent emergence of hypervirulent subtypes of avian influenza has underlined the potentially devastating effects of pandemic influenza. Were such a virus to acquire the ability to spread efficiently between humans, control would almost certainly be hampered by limited vaccine supplies unless global spread could be substantially delayed. Moreover, the large increases that have occurred in international air travel might be expected to lead to more rapid global dissemination than in previous pandemics. METHODS AND FINDINGS: To evaluate the potential of local control measures and travel restrictions to impede global dissemination, we developed stochastic models of the international spread of influenza based on extensions of coupled epidemic transmission models. These models have been shown to be capable of accurately forecasting local and global spread of epidemic and pandemic influenza. We show that under most scenarios restrictions on air travel are likely to be of surprisingly little value in delaying epidemics, unless almost all travel ceases very soon after epidemics are detected. CONCLUSIONS: Interventions to reduce local transmission of influenza are likely to be more effective at reducing the rate of global spread and less vulnerable to implementation delays than air travel restrictions. Nevertheless, under the most plausible scenarios, achievable delays are small compared with the time needed to accumulate substantial vaccine stocks.",2006 Jun 2,"['Cooper, Ben S', 'Pitman, Richard J', 'Edmunds, W. John', 'Gay, Nigel J']",PLoS Med,,,True
cda5efb9ec3966e7cd1df793ff55b51d9611eec3,PMC,Identifying strategies to improve access to credible and relevant information for public health professionals: a qualitative study,http://dx.doi.org/10.1186/1471-2458-6-89,PMC1456961,16597331,CC BY,"BACKGROUND: Movement towards evidence-based practices in many fields suggests that public health (PH) challenges may be better addressed if credible information about health risks and effective PH practices is readily available. However, research has shown that many PH information needs are unmet. In addition to reviewing relevant literature, this study performed a comprehensive review of existing information resources and collected data from two representative PH groups, focusing on identifying current practices, expressed information needs, and ideal systems for information access. METHODS: Nineteen individual interviews were conducted among employees of two domains in a state health department – communicable disease control and community health promotion. Subsequent focus groups gathered additional data on preferences for methods of information access and delivery as well as information format and content. Qualitative methods were used to identify themes in the interview and focus group transcripts. RESULTS: Informants expressed similar needs for improved information access including single portal access with a good search engine; automatic notification regarding newly available information; access to best practice information in many areas of interest that extend beyond biomedical subject matter; improved access to grey literature as well as to more systematic reviews, summaries, and full-text articles; better methods for indexing, filtering, and searching for information; and effective ways to archive information accessed. Informants expressed a preference for improving systems with which they were already familiar such as PubMed and listservs rather than introducing new systems of information organization and delivery. A hypothetical ideal model for information organization and delivery was developed based on informants' stated information needs and preferred means of delivery. Features of the model were endorsed by the subjects who reviewed it. CONCLUSION: Many critical information needs of PH practitioners are not being met efficiently or at all. We propose a dual strategy of: 1) promoting incremental improvements in existing information delivery systems based on the expressed preferences of the PH users of the systems and 2) the concurrent development and rigorous evaluation of new models of information organization and delivery that draw on successful resources already operating to deliver information to clinical medical practitioners.",2006 Apr 5,"['LaPelle, Nancy R', 'Luckmann, Roger', 'Simpson, E Hatheway', 'Martin, Elaine R']",BMC Public Health,,,True
a1b6c2b3b808e995697f94d9676d5d5c85180177,PMC,On pandemics and the duty to care: whose duty? who cares?,http://dx.doi.org/10.1186/1472-6939-7-5,PMC1459179,16626488,CC BY,"BACKGROUND: As a number of commentators have noted, SARS exposed the vulnerabilities of our health care systems and governance structures. Health care professionals (HCPs) and hospital systems that bore the brunt of the SARS outbreak continue to struggle with the aftermath of the crisis. Indeed, HCPs – both in clinical care and in public health – were severely tested by SARS. Unprecedented demands were placed on their skills and expertise, and their personal commitment to their profession was severely tried. Many were exposed to serious risk of morbidity and mortality, as evidenced by the World Health Organization figures showing that approximately 30% of reported cases were among HCPs, some of whom died from the infection. Despite this challenge, professional codes of ethics are silent on the issue of duty to care during communicable disease outbreaks, thus providing no guidance on what is expected of HCPs or how they ought to approach their duty to care in the face of risk. DISCUSSION: In the aftermath of SARS and with the spectre of a pandemic avian influenza, it is imperative that we (re)consider the obligations of HCPs for patients with severe infectious diseases, particularly diseases that pose risks to those providing care. It is of pressing importance that organizations representing HCPs give clear indication of what standard of care is expected of their members in the event of a pandemic. In this paper, we address the issue of special obligations of HCPs during an infectious disease outbreak. We argue that there is a pressing need to clarify the rights and responsibilities of HCPs in the current context of pandemic flu preparedness, and that these rights and responsibilities ought to be codified in professional codes of ethics. Finally, we present a brief historical accounting of the treatment of the duty to care in professional health care codes of ethics. SUMMARY: An honest and critical examination of the role of HCPs during communicable disease outbreaks is needed in order to provide guidelines regarding professional rights and responsibilities, as well as ethical duties and obligations. With this paper, we hope to open the social dialogue and advance the public debate on this increasingly urgent issue.",2006 Apr 20,"['Ruderman, Carly', 'Tracy, C Shawn', 'Bensimon, Cécile M', 'Bernstein, Mark', 'Hawryluck, Laura', 'Shaul, Randi Zlotnik', 'Upshur, Ross EG']",BMC Med Ethics,,,True
e8d81518d127913ce42b22fbdd96d416c4f82e44,PMC,Insertional protein engineering for analytical molecular sensing,http://dx.doi.org/10.1186/1475-2859-5-15,PMC1459189,16584558,CC BY,"The quantitative detection of low analyte concentrations in complex samples is becoming an urgent need in biomedical, food and environmental fields. Biosensors, being hybrid devices composed by a biological receptor and a signal transducer, represent valuable alternatives to non biological analytical instruments because of the high specificity of the biomolecular recognition. The vast range of existing protein ligands enable those macromolecules to be used as efficient receptors to cover a diversity of applications. In addition, appropriate protein engineering approaches enable further improvement of the receptor functioning such as enhancing affinity or specificity in the ligand binding. Recently, several protein-only sensors are being developed, in which either both the receptor and signal transducer are parts of the same protein, or that use the whole cell where the protein is produced as transducer. In both cases, as no further chemical coupling is required, the production process is very convenient. However, protein platforms, being rather rigid, restrict the proper signal transduction that necessarily occurs through ligand-induced conformational changes. In this context, insertional protein engineering offers the possibility to develop new devices, efficiently responding to ligand interaction by dramatic conformational changes, in which the specificity and magnitude of the sensing response can be adjusted up to a convenient level for specific analyte species. In this report we will discuss the major engineering approaches taken for the designing of such instruments as well as the relevant examples of resulting protein-only biosensors.",2006 Apr 3,"['Ferraz, Rosa María', 'Vera, Andrea', 'Arís, Anna', 'Villaverde, Antonio']",Microb Cell Fact,,,True
f38f3b112e4b702b60ba56be806d418bbb2b83c3,PMC,Immune Protection of Nonhuman Primates against Ebola Virus with Single Low-Dose Adenovirus Vectors Encoding Modified GPs,http://dx.doi.org/10.1371/journal.pmed.0030177,PMC1459482,16683867,CC0,"BACKGROUND: Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd) encoding the Ebola glycoprotein (GP) and nucleoprotein (NP) has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine. METHODS AND FINDINGS: To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 10(10) particles, two logs lower than that used previously. CONCLUSIONS: Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 10(10) rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate.",2006 Jun 16,"['Sullivan, Nancy J', 'Geisbert, Thomas W', 'Geisbert, Joan B', 'Shedlock, Devon J', 'Xu, Ling', 'Lamoreaux, Laurie', 'Custers, Jerome H. H. V', 'Popernack, Paul M', 'Yang, Zhi-Yong', 'Pau, Maria G', 'Roederer, Mario', 'Koup, Richard A', 'Goudsmit, Jaap', 'Jahrling, Peter B', 'Nabel, Gary J']",PLoS Med,,,True
2e2de8d6ebd368c062fed5770aa26a780bdc25b8,PMC,The interferon gamma gene polymorphism +874 A/T is associated with severe acute respiratory syndrome,http://dx.doi.org/10.1186/1471-2334-6-82,PMC1468415,16672072,CC BY,"BACKGROUND: Cytokines play important roles in antiviral action. We examined whether polymorphisms of IFN-γ,TNF-α and IL-10 affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). METHODS: A case-control study was carried out in 476 Chinese SARS patients and 449 healthy controls. We tested the polymorphisms of IFN-γ,TNF-α and IL-10 for their associations with SARS. RESULTS: IFN-γ +874A allele was associated with susceptibility to SARS in a dose-dependent manner (P < 0.001). Individuals with IFN-γ +874 AA and AT genotype had a 5.19-fold (95% Confidence Interval [CI], 2.78-9.68) and 2.57-fold (95% CI, 1.35-4.88) increased risk of developing SARS respectively. The polymorphisms of IL-10 and TNF-α were not associated with SARS susceptibility. CONCLUSION: IFN-γ +874A allele was shown to be a risk factor in SARS susceptibility.",2006 May 4,"['Chong, Wai Po', 'Ip, WK Eddie', 'Tso, Gloria Hoi Wan', 'Ng, Man Wai', 'Wong, Wilfred Hing Sang', 'Law, Helen Ka Wai', 'Yung, Raymond WH', 'Chow, Eudora Y', 'Au, KL', 'Chan, Eric YT', 'Lim, Wilina', 'Peiris, JS Malik', 'Lau, Yu Lung']",BMC Infect Dis,,,True
dce2c9d835e3ebbee3ff4e6868d5755ddec76b71,PMC,Microarray-based identification of antigenic variants of foot-and-mouth disease virus: a bioinformatics quality assessment,http://dx.doi.org/10.1186/1471-2164-7-117,PMC1481559,16709242,CC BY,"BACKGROUND: The evolution of viral quasispecies can influence viral pathogenesis and the response to antiviral treatments. Mutant clouds in infected organisms represent the first stage in the genetic and antigenic diversification of RNA viruses, such as foot and mouth disease virus (FMDV), an important animal pathogen. Antigenic variants of FMDV have been classically diagnosed by immunological or RT-PCR-based methods. DNA microarrays are becoming increasingly useful for the analysis of gene expression and single nucleotide polymorphisms (SNPs). Recently, a FMDV microarray was described to detect simultaneously the seven FMDV serotypes. These results encourage the development of new oligonucleotide microarrays to probe the fine genetic and antigenic composition of FMDV for diagnosis, vaccine design, and to gain insight into the molecular epidemiology of this pathogen. RESULTS: A FMDV microarray was designed and optimized to detect SNPs at a major antigenic site of the virus. A screening of point mutants of the genomic region encoding antigenic site A of FMDV C-S8c1 was achieved. The hybridization pattern of a mutant includes specific positive and negative signals as well as crosshybridization signals, which are of different intensity depending on the thermodynamic stability of each probe-target pair. Moreover, an array bioinformatic classification method was developed to evaluate the hybridization signals. This statistical analysis shows that the procedure allows a very accurate classification per variant genome. CONCLUSION: A specific approach based on a microarray platform aimed at distinguishing point mutants within an important determinant of antigenicity and host cell tropism, namely the G-H loop of capsid protein VP1, was developed. The procedure is of general applicability as a test for specificity and discriminatory power of microarray-based diagnostic procedures using multiple oligonucleotide probes.",2006 May 18,"['Martín, Verónica', 'Perales, Celia', 'Abia, David', 'Ortíz, Angel R', 'Domingo, Esteban', 'Briones, Carlos']",BMC Genomics,,,True
babad3896fca8ed7c89d9b785c08e7c42a48a6a2,PMC,Markers of exacerbation severity in chronic obstructive pulmonary disease,http://dx.doi.org/10.1186/1465-9921-7-74,PMC1481583,16686949,CC BY,"BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can experience 'exacerbations' of their conditions. An exacerbation is an event defined in terms of subjective descriptors or symptoms, namely dyspnoea, cough and sputum that worsen sufficiently to warrant a change in medical management. There is a need for reliable markers that reflect the pathological mechanisms that underlie exacerbation severity and that can be used as a surrogate to assess treatment effects in clinical studies. Little is known as to how existing study variables and suggested markers change in both the stable and exacerbation phases of COPD. In an attempt to find the best surrogates for exacerbations, we have reviewed the literature to identify which of these markers change in a consistent manner with the severity of the exacerbation event. METHODS: We have searched standard databases between 1966 to July 2004 using major keywords and terms. Studies that provided demographics, spirometry, potential markers, and clear eligibility criteria were included in this study. Central tendencies and dispersions for all the variables and markers reported and collected by us were first tabulated according to sample size and ATS/ERS 2004 Exacerbation Severity Levels I to III criteria. Due to the possible similarity of patients in Levels II and III, the data was also redefined into categories of exacerbations, namely out-patient (Level I) and in-patient (Levels II & III combined). For both approaches, we performed a fixed effect meta-analysis on each of the reported variables. RESULTS: We included a total of 268 studies reported between 1979 to July 2004. These studies investigated 142,407 patients with COPD. Arterial carbon dioxide tension and breathing rate were statistically different between all levels of exacerbation severity and between in out- and in-patient settings. Most other measures showed weak relationships with either level or setting, or they had insufficient data to permit meta-analysis. CONCLUSION: Arterial carbon dioxide and breathing rate varied in a consistent manner with exacerbation severity and patient setting. Many other measures showed weak correlations that should be further explored in future longitudinal studies or assessed using suggested mathematical modelling techniques.",2006 May 10,"['Franciosi, Luigi G', 'Page, Clive P', 'Celli, Bartolome R', 'Cazzola, Mario', 'Walker, Michael J', 'Danhof, Meindert', 'Rabe, Klaus F', 'Pasqua, Oscar E Della']",Respir Res,,,True
be57ba746b8fec268025df6afc68536fbd0188d8,PMC,In vitro inhibition of human influenza A virus replication by chloroquine,http://dx.doi.org/10.1186/1743-422X-3-39,PMC1481635,16729896,CC BY,"Chloroquine is a 9-aminoquinolone with well-known anti-malarial effects. It has biochemical properties that could be applied to inhibit viral replication. We report here that chloroquine is able to inhibit influenza A virus replication, in vitro, and the IC50s of chloroquine against influenza A viruses H1N1 and H3N2 are lower than the plasma concentrations reached during treatment of acute malaria. The potential of chloroquine to be added to the limited range of anti-influenza drugs should be explored further, particularly since antiviral drugs play a vital role in influenza pandemic preparedness.",2006 May 29,"['Ooi, Eng Eong', 'Chew, Janet Seok Wei', 'Loh, Jin Phang', 'Chua, Robert CS']",Virol J,,,True
8095e2bbc38cfeb18180deca4796293f5ce24eae,PMC,Amphotropic murine leukemia virus is preferentially attached to cholesterol-rich microdomains after binding to mouse fibroblasts,http://dx.doi.org/10.1186/1743-422X-3-21,PMC1483818,16579862,CC BY,"BACKGROUND: We have recently shown that amphotropic murine leukemia virus (A-MLV) can enter the mouse fibroblast cell line NIH3T3 via caveola-dependent endocytosis. But due to the size and omega-like shape of caveolae it is possible that A-MLV initially binds cells outside of caveolae. Rafts have been suggested to be pre-caveolae and we here investigate whether A-MLV initially binds to its receptor Pit2, a sodium-dependent phosphate transporter, in rafts or caveolae or outside these cholesterol-rich microdomains. RESULTS: Here, we show that a high amount of cell-bound A-MLV was attached to large rafts of NIH3T3 at the time of investigation. These large rafts were not enriched in caveolin-1, a major structural component of caveolae. In addition, they are rather of natural occurrence in NIH3T3 cells than a result of patching of smaller rafts by A-MLV. Thus cells incubated in parallel with vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped MLV particles showed the same pattern of large rafts as cells incubated with A-MLV, but VSV-G pseudotyped MLV particles did not show any preference to attach to these large microdomains. CONCLUSION: The high concentration of A-MLV particles bound to large rafts of NIH3T3 cells suggests a role of these microdomains in early A-MLV binding events.",2006 Apr 2,"['Beer, Christiane', 'Pedersen, Lene']",Virol J,,,True
3650b941642ddc9c3627fdb8d415f8c8b69a4158,PMC,Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants,http://dx.doi.org/10.1371/journal.pmed.0030237,PMC1483912,16796401,CC BY,"BACKGROUND: Experimental animal data show that protection against severe acute respiratory syndrome coronavirus (SARS-CoV) infection with human monoclonal antibodies (mAbs) is feasible. For an effective immune prophylaxis in humans, broad coverage of different strains of SARS-CoV and control of potential neutralization escape variants will be required. Combinations of virus-neutralizing, noncompeting mAbs may have these properties. METHODS AND FINDINGS: Human mAb CR3014 has been shown to completely prevent lung pathology and abolish pharyngeal shedding of SARS-CoV in infected ferrets. We generated in vitro SARS-CoV variants escaping neutralization by CR3014, which all had a single P462L mutation in the glycoprotein spike (S) of the escape virus. In vitro experiments confirmed that binding of CR3014 to a recombinant S fragment (amino acid residues 318–510) harboring this mutation was abolished. We therefore screened an antibody-phage library derived from blood of a convalescent SARS patient for antibodies complementary to CR3014. A novel mAb, CR3022, was identified that neutralized CR3014 escape viruses, did not compete with CR3014 for binding to recombinant S1 fragments, and bound to S1 fragments derived from the civet cat SARS-CoV-like strain SZ3. No escape variants could be generated with CR3022. The mixture of both mAbs showed neutralization of SARS-CoV in a synergistic fashion by recognizing different epitopes on the receptor-binding domain. Dose reduction indices of 4.5 and 20.5 were observed for CR3014 and CR3022, respectively, at 100% neutralization. Because enhancement of SARS-CoV infection by subneutralizing antibody concentrations is of concern, we show here that anti-SARS-CoV antibodies do not convert the abortive infection of primary human macrophages by SARS-CoV into a productive one. CONCLUSIONS: The combination of two noncompeting human mAbs CR3014 and CR3022 potentially controls immune escape and extends the breadth of protection. At the same time, synergy between CR3014 and CR3022 may allow for a lower total antibody dose to be administered for passive immune prophylaxis of SARS-CoV infection.",2006 Jul 4,"['ter Meulen, Jan', 'van den Brink, Edward N', 'Poon, Leo L. M', 'Marissen, Wilfred E', 'Leung, Cynthia S. W', 'Cox, Freek', 'Cheung, Chung Y', 'Bakker, Arjen Q', 'Bogaards, Johannes A', 'van Deventer, Els', 'Preiser, Wolfgang', 'Doerr, Hans Wilhelm', 'Chow, Vincent T', 'de Kruif, John', 'Peiris, Joseph S. M', 'Goudsmit, Jaap']",PLoS Med,,,True
8c640872048570b0a671ec08c83ef6cbebcdd78e,PMC,Selection of a set of reliable reference genes for quantitative real-time PCR in normal equine skin and in equine sarcoids,http://dx.doi.org/10.1186/1472-6750-6-24,PMC1484482,16643647,CC BY,"BACKGROUND: Real-time quantitative PCR can be a very powerful and accurate technique to examine gene transcription patterns in different biological conditions. One of the critical steps in comparing transcription profiles is accurate normalisation. In most of the studies published on real-time PCR in horses, normalisation occurred against only one reference gene, usually GAPDH or ACTB, without validation of its expression stability. This might result in unreliable conclusions, because it has been demonstrated that the expression levels of so called ""housekeeping genes"" may vary considerably in different tissues, cell types or disease stages, particularly in clinical samples associated with malignant disease. The goal of this study was to establish a reliable set of reference genes for studies concerning normal equine skin and equine sarcoids, which are the most common skin tumour in horses. RESULTS: In the present study the gene transcription levels of 6 commonly used reference genes (ACTB, B2M, HPRT1, UBB, TUBA1 and RPL32) were determined in normal equine skin and in equine sarcoids. After applying the geNorm applet to this set of genes, TUBA1, ACTB and UBB were found to be most stable in normal skin and B2M, ACTB and UBB in equine sarcoids. CONCLUSION: Based on these results, TUBA1, ACTB and UBB, respectively B2M, ACTB and UBB can be proposed as reference gene panels for accurate normalisation of quantitative data for normal equine skin, respectively equine sarcoids. When normal skin and equine sarcoids are compared, the use of the geometric mean of UBB, ACTB and B2M can be recommended as a reliable and accurate normalisation factor.",2006 Apr 27,"['Bogaert, Lies', 'Van Poucke, Mario', 'De Baere, Cindy', 'Peelman, Luc', 'Gasthuys, Frank', 'Martens, Ann']",BMC Biotechnol,,,True
b1f86a8d26afcb49621b2b3aba8eaf1851b95315,PMC,Combined fluticasone propionate and salmeterol reduces RSV infection more effectively than either of them alone in allergen-sensitized mice,http://dx.doi.org/10.1186/1743-422X-3-32,PMC1488829,16719922,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in infants and is a risk factor for the development of asthma. Allergic asthmatics are more susceptible to RSV infection and viral exacerbation. METHODS: Since the effectiveness of corticosteroids in treating RSV infection has been controversial, we tested fluticasone propionate (FP) and salmeterol (Sal) alone versus FP plus Sal (FPS) on RSV-induced airway inflammation. Mice were sensitized and challenged with ovalbumin (OVA) and infected with RSV. Following infection they were treated with FP, Sal, or FPS intranasally and airway hyperreactivity (AHR), inflammation and RSV titers were examined. RESULTS: The group treated with FPS showed significantly lower AHR compared to the group treated with FP or Sal alone. The group treated with FP alone showed slightly decreased (non-significant) AHR compared to controls. Treatment with FPS resulted in significant decreases in the percentage of eosinophils and neutrophils in bronchoalveolar lavage fluid and in lung pathology compared to FP or Sal. FP alone decreased eosinophils but not neutrophils or lymphocytes, while Sal alone decreased eosinophils and neutrophils but not lymphocytes. FPS treatment of mice infected with RSV in the absence of allergen sensitization resulted in a 50% decrease of RSV titer in the lung and a reduction in neutrophils compared to FP or Sal. CONCLUSION: Together, these results indicate that fluticasone in combination with salmeterol is a more effective treatment for decreasing airway hyperreactivity and inflammation than either of them alone in allergen-sensitized, RSV-infected mice.",2006 May 23,"['Singam, Rajeswari', 'Jena, Prasanna K', 'Behera, Sumita', 'Hellermann, Gary R', 'Lockey, Richard F', 'Ledford, Dennis', 'Mohapatra, Shyam S']",Virol J,,,True
a0f13b751004e29186fa070fdffa2e876815e41a,PMC,"Antibiotic resistance as a global threat: Evidence from China, Kuwait and the United States",http://dx.doi.org/10.1186/1744-8603-2-6,PMC1502134,16603071,CC BY,"BACKGROUND: Antimicrobial resistance is an under-appreciated threat to public health in nations around the globe. With globalization booming, it is important to understand international patterns of resistance. If countries already experience similar patterns of resistance, it may be too late to worry about international spread. If large countries or groups of countries that are likely to leap ahead in their integration with the rest of the world – China being the standout case – have high and distinctive patterns of resistance, then a coordinated response could substantially help to control the spread of resistance. The literature to date provides only limited evidence on these issues. METHODS: We study the recent patterns of antibiotic resistance in three geographically separated, and culturally and economically distinct countries – China, Kuwait and the United States – to gauge the range and depth of this global health threat, and its potential for growth as globalization expands. Our primary measures are the prevalence of resistance of specific bacteria to specific antibiotics. We also propose and illustrate methods for aggregating specific ""bug-drug"" data. We use these aggregate measures to summarize the resistance pattern for each country and to study the extent of correlation between countries' patterns of drug resistance. RESULTS: We find that China has the highest level of antibiotic resistance, followed by Kuwait and the U.S. In a study of resistance patterns of several most common bacteria in China in 1999 and 2001, the mean prevalence of resistance among hospital-acquired infections was as high as 41% (with a range from 23% to 77%) and that among community- acquired infections was 26% (with a range from 15% to 39%). China also has the most rapid growth rate of resistance (22% average growth in a study spanning 1994 to 2000). Kuwait is second (17% average growth in a period from 1999 to 2003), and the U.S. the lowest (6% from 1999 to 2002). Patterns of resistance across the three countries are not highly correlated; the most correlated were China and Kuwait, followed by Kuwait and the U.S., and the least correlated pair was China and the U.S. CONCLUSION: Antimicrobial resistance is a serious and growing problem in all three countries. To date, there is not strong international convergence in the countries' resistance patterns. This finding may change with the greater international travel that will accompany globalization. Future research on the determinants of drug resistance patterns, and their international convergence or divergence, should be a priority.",2006 Apr 7,"['Zhang, Ruifang', 'Eggleston, Karen', 'Rotimi, Vincent', 'Zeckhauser, Richard J']",Global Health,,,True
8b86e36ed4cc2b952e49ea978844332007c00439,PMC,The basic principles of migration health: Population mobility and gaps in disease prevalence,http://dx.doi.org/10.1186/1742-7622-3-3,PMC1513225,16674820,CC BY,"Currently, migrants and other mobile individuals, such as migrant workers and asylum seekers, are an expanding global population of growing social, demographic and political importance. Disparities often exist between a migrant population's place of origin and its destination, particularly with relation to health determinants. The effects of those disparities can be observed at both individual and population levels. Migration across health and disease disparities influences the epidemiology of certain diseases globally and in nations receiving migrants. While specific disease-based outcomes may vary between migrant group and location, general epidemiological principles may be applied to any situation where numbers of individuals move between differences in disease prevalence. Traditionally, migration health activities have been designed for national application and lack an integrated international perspective. Present and future health challenges related to migration may be more effectively addressed through collaborative global undertakings. This paper reviews the epidemiological relationships resulting from health disparities bridged by migration and describes the growing role of migration and population mobility in global disease epidemiology. The implications for national and international health policy and program planning are presented.",2006 May 4,"['Gushulak, Brian D', 'MacPherson, Douglas W']",Emerg Themes Epidemiol,,,True
362f9e6b508a42ffebfd1a95d146955d59c7cea0,PMC,Quantitative prediction of mouse class I MHC peptide binding affinity using support vector machine regression (SVR) models,http://dx.doi.org/10.1186/1471-2105-7-182,PMC1513606,16579851,CC BY,"BACKGROUND: The binding between peptide epitopes and major histocompatibility complex proteins (MHCs) is an important event in the cellular immune response. Accurate prediction of the binding between short peptides and the MHC molecules has long been a principal challenge for immunoinformatics. Recently, the modeling of MHC-peptide binding has come to emphasize quantitative predictions: instead of categorizing peptides as ""binders"" or ""non-binders"" or as ""strong binders"" and ""weak binders"", recent methods seek to make predictions about precise binding affinities. RESULTS: We developed a quantitative support vector machine regression (SVR) approach, called SVRMHC, to model peptide-MHC binding affinities. As a non-linear method, SVRMHC was able to generate models that out-performed existing linear models, such as the ""additive method"". By adopting a new ""11-factor encoding"" scheme, SVRMHC takes into account similarities in the physicochemical properties of the amino acids constituting the input peptides. When applied to MHC-peptide binding data for three mouse class I MHC alleles, the SVRMHC models produced more accurate predictions than those produced previously. Furthermore, comparisons based on Receiver Operating Characteristic (ROC) analysis indicated that SVRMHC was able to out-perform several prominent methods in identifying strongly binding peptides. CONCLUSION: As a method with demonstrated performance in the quantitative modeling of MHC-peptide binding and in identifying strong binders, SVRMHC is a promising immunoinformatics tool with not inconsiderable future potential.",2006 Mar 31,"['Liu, Wen', 'Meng, Xiangshan', 'Xu, Qiqi', 'Flower, Darren R', 'Li, Tongbin']",BMC Bioinformatics,,,True
4485f96496a208b7e77c9f53a8feb468483776db,PMC,Silencing Viral Infection,http://dx.doi.org/10.1371/journal.pmed.0030242,PMC1518680,16848617,CC BY,The authors describe recent progress and obstacles to harnessing RNA interference to prevent or treat viral infection.,2006 Jul 25,"['Dykxhoorn, Derek M', 'Lieberman, Judy']",PLoS Med,,,True
4db3931c4b24ae432d68b7e24f593b1272445523,PMC,Differentially profiling the low-expression transcriptomes of human hepatoma using a novel SSH/microarray approach,http://dx.doi.org/10.1186/1471-2164-7-131,PMC1522022,16737534,CC BY,"BACKGROUND: The main limitation in performing genome-wide gene-expression profiling is the assay of low-expression genes. Approaches with high throughput and high sensitivity for assaying low-expression transcripts are urgently needed for functional genomic studies. Combination of the suppressive subtractive hybridization (SSH) and cDNA microarray techniques using the subtracted cDNA clones as probes printed on chips has greatly improved the efficiency for fishing out the differentially expressed clones and has been used before. However, it remains tedious and inefficient sequencing works for identifying genes including the great number of redundancy in the subtracted amplicons, and sacrifices the original advantages of high sensitivity of SSH in profiling low-expression transcriptomes. RESULTS: We modified the previous combination of SSH and microarray methods by directly using the subtracted amplicons as targets to hybridize the pre-made cDNA microarrays (named as ""SSH/microarray""). mRNA prepared from three pairs of hepatoma and non-hepatoma liver tissues was subjected to the SSH/microarray assays, as well as directly to regular cDNA microarray assays for comparison. As compared to the original SSH and microarray combination assays, the modified SSH/microarray assays allowed for much easier inspection of the subtraction efficiency and identification of genes in the subtracted amplicons without tedious and inefficient sequencing work. On the other hand, 5015 of the 9376 genes originally filtered out by the regular cDNA microarray assays because of low expression became analyzable by the SSH/microarray assays. Moreover, the SSH/microarray assays detected about ten times more (701 vs. 69) HCC differentially expressed genes (at least a two-fold difference and P < 0.01), particularly for those with rare transcripts, than did the regular cDNA microarray assays. The differential expression was validated in 9 randomly selected genes in 18 pairs of hepatoma/non-hepatoma liver tissues using quantitative RT-PCR. The SSH/microarray approaches resulted in identifying many differentially expressed genes implicated in the regulation of cell cycle, cell death, signal transduction and cell morphogenesis, suggesting the involvement of multi-biological processes in hepato-carcinogenesis. CONCLUSION: The modified SSH/microarray approach is a simple but high-sensitive and high-efficient tool for differentially profiling the low-expression transcriptomes. It is most adequate for applying to functional genomic studies.",2006 May 31,"['Pan, Yi-Shin', 'Lee, Yun-Shien', 'Lee, Yung-Lin', 'Lee, Wei-Chen', 'Hsieh, Sen-Yung']",BMC Genomics,,,True
dfddc7262329261ef41c6da4bd8a56ec2c3f81dc,PMC,Differentially profiling the low-expression transcriptomes of human hepatoma using a novel SSH/microarray approach,http://dx.doi.org/10.1186/1471-2164-7-131,PMC1522022,16737534,CC BY,"BACKGROUND: The main limitation in performing genome-wide gene-expression profiling is the assay of low-expression genes. Approaches with high throughput and high sensitivity for assaying low-expression transcripts are urgently needed for functional genomic studies. Combination of the suppressive subtractive hybridization (SSH) and cDNA microarray techniques using the subtracted cDNA clones as probes printed on chips has greatly improved the efficiency for fishing out the differentially expressed clones and has been used before. However, it remains tedious and inefficient sequencing works for identifying genes including the great number of redundancy in the subtracted amplicons, and sacrifices the original advantages of high sensitivity of SSH in profiling low-expression transcriptomes. RESULTS: We modified the previous combination of SSH and microarray methods by directly using the subtracted amplicons as targets to hybridize the pre-made cDNA microarrays (named as ""SSH/microarray""). mRNA prepared from three pairs of hepatoma and non-hepatoma liver tissues was subjected to the SSH/microarray assays, as well as directly to regular cDNA microarray assays for comparison. As compared to the original SSH and microarray combination assays, the modified SSH/microarray assays allowed for much easier inspection of the subtraction efficiency and identification of genes in the subtracted amplicons without tedious and inefficient sequencing work. On the other hand, 5015 of the 9376 genes originally filtered out by the regular cDNA microarray assays because of low expression became analyzable by the SSH/microarray assays. Moreover, the SSH/microarray assays detected about ten times more (701 vs. 69) HCC differentially expressed genes (at least a two-fold difference and P < 0.01), particularly for those with rare transcripts, than did the regular cDNA microarray assays. The differential expression was validated in 9 randomly selected genes in 18 pairs of hepatoma/non-hepatoma liver tissues using quantitative RT-PCR. The SSH/microarray approaches resulted in identifying many differentially expressed genes implicated in the regulation of cell cycle, cell death, signal transduction and cell morphogenesis, suggesting the involvement of multi-biological processes in hepato-carcinogenesis. CONCLUSION: The modified SSH/microarray approach is a simple but high-sensitive and high-efficient tool for differentially profiling the low-expression transcriptomes. It is most adequate for applying to functional genomic studies.",2006 May 31,"['Pan, Yi-Shin', 'Lee, Yun-Shien', 'Lee, Yung-Lin', 'Lee, Wei-Chen', 'Hsieh, Sen-Yung']",BMC Genomics,,,False
7aac0f55c8b869e13f1c2678207430bc9203d65e,PMC,Design of microarray probes for virus identification and detection of emerging viruses at the genus level,http://dx.doi.org/10.1186/1471-2105-7-232,PMC1523220,16643672,CC BY,"BACKGROUND: Most virus detection methods are geared towards the detection of specific single viruses or just a few known targets, and lack the capability to uncover the novel viruses that cause emerging viral infections. To address this issue, we developed a computational method that identifies the conserved viral sequences at the genus level for all viral genomes available in GenBank, and established a virus probe library. The virus probes are used not only to identify known viruses but also for discerning the genera of emerging or uncharacterized ones. RESULTS: Using the microarray approach, the identity of the virus in a test sample is determined by the signals of both genus and species-specific probes. The genera of emerging and uncharacterized viruses are determined based on hybridization of the viral sequences to the conserved probes for the existing viral genera. A detection and classification procedure to determine the identity of a virus directly from detection signals results in the rapid identification of the virus. CONCLUSION: We have demonstrated the validity and feasibility of the above strategy with a small number of viral samples. The probe design algorithm can be applied to any publicly available viral sequence database. The strategy of using separate genus and species probe sets enables the use of a straightforward virus identity calculation directly based on the hybridization signals. Our virus identification strategy has great potential in the diagnosis of viral infections. The virus genus and specific probe database and the associated summary tables are available at",2006 Apr 28,"['Chou, Cheng-Chung', 'Lee, Te-Tsui', 'Chen, Chun-Houh', 'Hsiao, Hsiang-Yun', 'Lin, Yi-Ling', 'Ho, Mei-Shang', 'Yang, Pan-Chyr', 'Peck, Konan']",BMC Bioinformatics,,,True
40500cd7ae5b4e116e8b13e5408e7dfd96d43ab4,PMC,"From Functional Genomics to Functional Immunomics: New Challenges, Old Problems, Big Rewards",http://dx.doi.org/10.1371/journal.pcbi.0020081,PMC1523295,16863395,CC BY,"The development of DNA microarray technology a decade ago led to the establishment of functional genomics as one of the most active and successful scientific disciplines today. With the ongoing development of immunomic microarray technology—a spatially addressable, large-scale technology for measurement of specific immunological response—the new challenge of functional immunomics is emerging, which bears similarities to but is also significantly different from functional genomics. Immunonic data has been successfully used to identify biological markers involved in autoimmune diseases, allergies, viral infections such as human immunodeficiency virus (HIV), influenza, diabetes, and responses to cancer vaccines. This review intends to provide a coherent vision of this nascent scientific field, and speculate on future research directions. We discuss at some length issues such as epitope prediction, immunomic microarray technology and its applications, and computation and statistical challenges related to functional immunomics. Based on the recent discovery of regulation mechanisms in T cell responses, we envision the use of immunomic microarrays as a tool for advances in systems biology of cellular immune responses, by means of immunomic regulatory network models.",2006 Jul 28,"['Braga-Neto, Ulisses M', 'Marques, Ernesto T. A']",PLoS Comput Biol,,,True
48d2cdd1975a60aa6d7ab15b51b523b10529b038,PMC,The role of single N-glycans in proteolytic processing and cell surface transport of the Lassa virus glycoprotein GP-C,http://dx.doi.org/10.1186/1743-422X-3-41,PMC1524727,16737539,CC BY,"Lassa virus glycoprotein is synthesised as a precursor (preGP-C) into the lumen of the endoplasmic reticulum. After cotranslational cleavage of the signal peptide, the immature GP-C is posttranslationally processed into the N-terminal subunit GP-1 and the C-terminal subunit GP-2 by the host cell subtilase SKI-1/S1P. The glycoprotein precursor contains eleven potential N-glycosylation sites. In this report, we investigated the effect of each N-glycan on proteolytic cleavage and cell surface transport by disrupting the consensus sequences of eleven potential N-glycan attachment sites individually. Five glycoprotein mutants with disrupted N-glycosylation sites were still proteolytically processed, whereas the remaining N-glycosylation sites are necessary for GP-C cleavage. Despite the lack of proteolytic processing, all cleavage-defective mutants were transported to the cell surface and remained completely endo H-sensitive. The findings indicate that N-glycans are needed for correct conformation of GP-C in order to be cleaved by SKI-1/S1P.",2006 May 31,"['Eichler, Robert', 'Lenz, Oliver', 'Garten, Wolfgang', 'Strecker, Thomas']",Virol J,,,True
fafa45b4080e37b2d37450168738d991a0399343,PMC,"The synergistic effect of IFN-α and IFN-γ against HSV-2 replication in Vero cells is not interfered by the plant antiviral 1-cinnamoyl-3, 11-dihydroxymeliacarpin",http://dx.doi.org/10.1186/1743-422X-3-45,PMC1525181,16772029,CC BY,"BACKGROUND: Recent studies have shown that gamma interferon (IFN-γ) synergizes with IFN-α/β to inhibit herpes simplex virus type 1 (HSV-1) replication in vitro. Since IFN response represents an early host defense event against viral infection and the fact that treatment with meliacine, a plant antiviral, ameliorate the severity of the herpetic infection in female mice infected intravaginally with HSV-2, we wanted to investigate whether the administration of meliacine to HSV-2 infected mice could altered the homoestasis of IFNs host response. For this purpose we studied the effect of the compound 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), which is the responsible for meliacine antiviral action, on the HSV-2 inhibition exerted by IFN α, IFN-γ or their combination. RESULTS: We have found that like HSV-1, IFN-γ synergizes with IFN-α to inhibit HSV-2 replication in Vero cells. While treatment with IFN-α or IFN-γ alone has weak antiviral action, HSV-2 plaque formation, viral replication and the onset of viral CPE in Vero cells are synergistically inhibited by interferon combination. In addition, CDM treatment contributes to protect cells from virus cytopathic effect and causes a strong inhibition of HSV-2 titer. Moreover, the presence of CDM for 2 h before IFN induction, during the 16 h induction period, only for 24 h after infection or during the complete IFN treatment period, reduces virus yields in an additive way without affecting IFN antiviral action. CONCLUSION: The results reported here indicated that the presence of CDM did not alter the antiviral activity of IFN-α, IFN-γ or the synergism exerted by their combination. As a result we can envision that the administration of CDM in vivo could not affect the biological activity of IFNs, which are so important mediators of the innate resistance to HSV-2 infection.",2006 Jun 13,"['Petrera, Erina', 'Coto, Celia E']",Virol J,,,True
02b8dea56378d11fe92d6a60ff37a34b0d6ea63e,PMC,CD147 overexpression on synoviocytes in rheumatoid arthritis enhances matrix metalloproteinase production and invasiveness of synoviocytes,http://dx.doi.org/10.1186/ar1899,PMC1526600,16507143,CC BY,"Macrophage-like synoviocytes and fibroblast-like synoviocytes (FLS) are known as the most active cells of rheumatoid arthritis (RA) and are close to the articular cartilage in a position enabling them to invade the cartilage. Macrophage-like synoviocytes and FLS expression of matrix metalloproteinases (MMPs) and their interaction has aroused great interest. The present article studied the expression of CD147, also called extracellular matrix metalloproteinase inducer, on monocytes/macrophages and FLS from RA patients and its potential role in enhancing MMPs and the invasiveness of synoviocytes. Expression of CD147 on FLS derived from RA patients and from osteoarthritis patients, and expression of CD147 on monocytes/macrophages from rheumatic synovial fluid and healthy peripheral blood were analyzed by flow cytometry. The levels of CD147, MMP-2 and MMP-9 mRNA in FLS were detected by RT-PCR. The role of CD147 in MMP production and the cells' invasiveness in vitro were studied by the co-culture of FLS with the human THP-1 cell line or monocytes/macrophages, by gel zymography and by invasion assay. The results showed that the expression of CD147 was higher on RA FLS than on osteoarthritis FLS and was higher on monocytes/macrophages from rheumatic synovial fluid than on monocytes/macrophages from healthy peripheral blood. RT-PCR showed that the expressions of CD147, MMP-2 and MMP-9 mRNA was higher in RA FLS than in osteoarthritis FLS. A significantly elevated secretion and activation of MMP-2 and MMP-9 were observed in RA FLS co-cultured with differentiated THP-1 cells or RA synovial monocytes/macrophages, compared with those co-cultured with undifferentiated THP-1 cells or healthy control peripheral blood monocytes. Invasion assays showed an increased number of invading cells in the co-cultured RA FLS with differentiated THP-1 cells or RA synovial monocytes/macrophages. CD147 antagonistic peptide inhibited the MMP production and the invasive potential. Our studies demonstrated that the CD147 overexpression on monocytes/macrophages and FLS in RA patients may be responsible for the enhanced MMP secretion and activation and for the invasiveness of synoviocytes. These findings suggest that CD147 may be one of the important factors in progressive joint destruction of RA and that CD147 may be a potential therapeutic target in RA treatment.",2006 Feb 8,"['Zhu, Ping', 'Lu, Ning', 'Shi, Zhan-guo', 'Zhou, Jun', 'Wu, Zhen-biao', 'Yang, Yong', 'Ding, Jin', 'Chen, Zhi-nan']",Arthritis Res Ther,,,True
2bd6e33d92632dfcba4056a2d7355ced5b7ab1fd,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,True
76481505399740984fe9bf11fdfec984fbf11e32,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,True
f6686ac18c05ec72b33fbed5485fc922531d2529,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,True
84ad793db6fd5878929791f4a2f50943881206f1,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,True
6fe7dbbe77090cf3a1ac5ce68b0aca877c08dd71,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,True
f529616d665d71bd3aeb449334a8dc0e345e9e49,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,False
8a673053b68dec16bccca1928f8f584351633eaa,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,False
f4f5ea10677874343c578304f0c7d9d0f9a0fae1,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,False
0f8893808429b542f91b20eb3b34581fe65296bc,PMC,Reducing the Impact of the Next Influenza Pandemic Using Household-Based Public Health Interventions,http://dx.doi.org/10.1371/journal.pmed.0030361,PMC1526768,16881729,CC BY,"BACKGROUND: The outbreak of highly pathogenic H5N1 influenza in domestic poultry and wild birds has caused global concern over the possible evolution of a novel human strain [1]. If such a strain emerges, and is not controlled at source [2,3], a pandemic is likely to result. Health policy in most countries will then be focused on reducing morbidity and mortality. METHODS AND FINDINGS: We estimate the expected reduction in primary attack rates for different household-based interventions using a mathematical model of influenza transmission within and between households. We show that, for lower transmissibility strains [2,4], the combination of household-based quarantine, isolation of cases outside the household, and targeted prophylactic use of anti-virals will be highly effective and likely feasible across a range of plausible transmission scenarios. For example, for a basic reproductive number (the average number of people infected by a typically infectious individual in an otherwise susceptible population) of 1.8, assuming only 50% compliance, this combination could reduce the infection (symptomatic) attack rate from 74% (49%) to 40% (27%), requiring peak quarantine and isolation levels of 6.2% and 0.8% of the population, respectively, and an overall anti-viral stockpile of 3.9 doses per member of the population. Although contact tracing may be additionally effective, the resources required make it impractical in most scenarios. CONCLUSIONS: National influenza pandemic preparedness plans currently focus on reducing the impact associated with a constant attack rate, rather than on reducing transmission. Our findings suggest that the additional benefits and resource requirements of household-based interventions in reducing average levels of transmission should also be considered, even when expected levels of compliance are only moderate.",2006 Sep 8,"['Wu, Joseph T', 'Riley, Steven', 'Fraser, Christophe', 'Leung, Gabriel M']",PLoS Med,,,False
104a23fead757f1b8272ae0813db98b413375ae0,PMC,Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells,http://dx.doi.org/10.1186/1465-9921-7-98,PMC1533820,16834785,CC BY,"BACKGROUND: Although pneumococcal pneumonia is one of the most common causes of death due to infectious diseases, little is known about pneumococci-lung cell interaction. Herein we tested the hypothesis that pneumococci activated pulmonary epithelial cell cytokine release by c-Jun-NH(2)-terminal kinase (JNK) METHODS: Human bronchial epithelial cells (BEAS-2B) or epithelial HEK293 cells were infected with S. pneumoniae R6x and cytokine induction was measured by RT-PCR, ELISA and Bioplex assay. JNK-phosphorylation was detected by Western blot and nuclear signaling was assessed by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). JNK was modulated by the small molecule inhibitor SP600125 and AP1 by transfection of a dominant negative mutant. RESULTS: S. pneumoniae induced the release of distinct CC and CXC, as well as Th1 and Th2 cytokines and growth factors by human lung epithelial cell line BEAS-2B. Furthermore, pneumococci infection resulted in JNK phosphorylation in BEAS-2B cells. Inhibition of JNK by small molecule inhibitor SP600125 reduced pneumococci-induced IL-8 mRNA expression and release of IL-8 and IL-6. One regulator of the il8 promoter is JNK-phosphorylated activator protein 1 (AP-1). We showed that S. pneumoniae time-dependently induced DNA binding of AP-1 and its phosphorylated subunit c-Jun with a maximum at 3 to 5 h after infection. Recruitment of Ser(63/73)-phosphorylated c-Jun and RNA polymerase II to the endogenous il8 promoter was found 2 h after S. pneumoniae infection by chromatin immunoprecipitation. AP-1 repressor A-Fos reduced IL-8 release by TLR2-overexpressing HEK293 cells induced by pneumococci but not by TNFα. Antisense-constructs targeting the AP-1 subunits Fra1 and Fra2 had no inhibitory effect on pneumococci-induced IL-8 release. CONCLUSION: S. pneumoniae-induced IL-8 expression by human epithelial BEAS-2B cells depended on activation of JNK and recruitment of phosphorylated c-Jun to the il8 promoter.",2006 Jul 12,"['Schmeck, Bernd', 'Moog, Kerstin', 'Zahlten, Janine', 'van Laak, Vincent', ""N'Guessan, Philippe Dje"", 'Opitz, Bastian', 'Rosseau, Simone', 'Suttorp, Norbert', 'Hippenstiel, Stefan']",Respir Res,,,True
adeb15fc330fe6710ad1c979d0a33035b52f3ba0,PMC,Lung epithelium as a sentinel and effector system in pneumonia – molecular mechanisms of pathogen recognition and signal transduction,http://dx.doi.org/10.1186/1465-9921-7-97,PMC1533821,16827942,CC BY,"Pneumonia, a common disease caused by a great diversity of infectious agents is responsible for enormous morbidity and mortality worldwide. The bronchial and lung epithelium comprises a large surface between host and environment and is attacked as a primary target during lung infection. Besides acting as a mechanical barrier, recent evidence suggests that the lung epithelium functions as an important sentinel system against pathogens. Equipped with transmembranous and cytosolic pathogen-sensing pattern recognition receptors the epithelium detects invading pathogens. A complex signalling results in epithelial cell activation, which essentially participates in initiation and orchestration of the subsequent innate and adaptive immune response. In this review we summarize recent progress in research focussing on molecular mechanisms of pathogen detection, host cell signal transduction, and subsequent activation of lung epithelial cells by pathogens and their virulence factors and point to open questions. The analysis of lung epithelial function in the host response in pneumonia may pave the way to the development of innovative highly needed therapeutics in pneumonia in addition to antibiotics.",2006 Jul 8,"['Hippenstiel, Stefan', 'Opitz, Bastian', 'Schmeck, Bernd', 'Suttorp, Norbert']",Respir Res,,,True
ea23fbae1cee451e0beca6f5b2f6684519f63a67,PMC,Genome Annotation Transfer Utility (GATU): rapid annotation of viral genomes using a closely related reference genome,http://dx.doi.org/10.1186/1471-2164-7-150,PMC1534038,16772042,CC BY,"BACKGROUND: Since DNA sequencing has become easier and cheaper, an increasing number of closely related viral genomes have been sequenced. However, many of these have been deposited in GenBank without annotations, severely limiting their value to researchers. While maintaining comprehensive genomic databases for a set of virus families at the Viral Bioinformatics Resource Center and Viral Bioinformatics – Canada , we found that researchers were unnecessarily spending time annotating viral genomes that were close relatives of already annotated viruses. We have therefore designed and implemented a novel tool, Genome Annotation Transfer Utility (GATU), to transfer annotations from a previously annotated reference genome to a new target genome, thereby greatly reducing this laborious task. RESULTS: GATU transfers annotations from a reference genome to a closely related target genome, while still giving the user final control over which annotations should be included. GATU also detects open reading frames present in the target but not the reference genome and provides the user with a variety of bioinformatics tools to quickly determine if these ORFs should also be included in the annotation. After this process is complete, GATU saves the newly annotated genome as a GenBank, EMBL or XML-format file. The software is coded in Java and runs on a variety of computer platforms. Its user-friendly Graphical User Interface is specifically designed for users trained in the biological sciences. CONCLUSION: GATU greatly simplifies the initial stages of genome annotation by using a closely related genome as a reference. It is not intended to be a gene prediction tool or a ""complete"" annotation system, but we have found that it significantly reduces the time required for annotation of genes and mature peptides as well as helping to standardize gene names between related organisms by transferring reference genome annotations to the target genome. The program is freely available under the General Public License and can be accessed along with documentation and tutorial from .",2006 Jun 13,"['Tcherepanov, Vasily', 'Ehlers, Angelika', 'Upton, Chris']",BMC Genomics,,,True
6cfcbd2a102a3666d0d168f9bdaba0b2107fc8bd,PMC,Reliability of case definitions for public health surveillance assessed by Round-Robin test methodology,http://dx.doi.org/10.1186/1471-2458-6-129,PMC1538585,16686946,CC BY,"BACKGROUND: Case definitions have been recognized to be important elements of public health surveillance systems. They are to assure comparability and consistency of surveillance data and have crucial impact on the sensitivity and the positive predictive value of a surveillance system. The reliability of case definitions has rarely been investigated systematically. METHODS: We conducted a Round-Robin test by asking all 425 local health departments (LHD) and the 16 state health departments (SHD) in Germany to classify a selection of 68 case examples using case definitions. By multivariate analysis we investigated factors linked to classification agreement with a gold standard, which was defined by an expert panel. RESULTS: A total of 7870 classifications were done by 396 LHD (93%) and all SHD. Reporting sensitivity was 90.0%, positive predictive value 76.6%. Polio case examples had the lowest reporting precision, salmonellosis case examples the highest (OR = 0.008; CI: 0.005–0.013). Case definitions with a check-list format of clinical criteria resulted in higher reporting precision than case definitions with a narrative description (OR = 3.08; CI: 2.47–3.83). Reporting precision was higher among SHD compared to LHD (OR = 1.52; CI: 1.14–2.02). CONCLUSION: Our findings led to a systematic revision of the German case definitions and build the basis for general recommendations for the creation of case definitions. These include, among others, that testable yes/no criteria in a check-list format is likely to improve reliability, and that software used for data transmission should be designed in strict accordance with the case definitions. The findings of this study are largely applicable to case definitions in many other countries or international networks as they share the same structural and editorial characteristics of the case definitions evaluated in this study before their revision.",2006 May 10,"['Krause, Gérard', 'Brodhun, Bonita', 'Altmann, Doris', 'Claus, Hermann', 'Benzler, Justus']",BMC Public Health,,,True
67727dc7bb076ef6ddeb55c754af98e672ee60e0,PMC,Live bacterial vaccines – a review and identification of potential hazards,http://dx.doi.org/10.1186/1475-2859-5-23,PMC1538998,16796731,CC BY,"The use of live bacteria to induce an immune response to itself or to a carried vaccine component is an attractive vaccine strategy. Advantages of live bacterial vaccines include their mimicry of a natural infection, intrinsic adjuvant properties and their possibility to be administered orally. Derivatives of pathogenic and non-pathogenic food related bacteria are currently being evaluated as live vaccines. However, pathogenic bacteria demands for attenuation to weaken its virulence. The use of bacteria as vaccine delivery vehicles implies construction of recombinant strains that contain the gene cassette encoding the antigen. With the increased knowledge of mucosal immunity and the availability of genetic tools for heterologous gene expression the concept of live vaccine vehicles gains renewed interest. However, administration of live bacterial vaccines poses some risks. In addition, vaccination using recombinant bacteria results in the release of live recombinant organisms into nature. This places these vaccines in the debate on application of genetically modified organisms. In this review we give an overview of live bacterial vaccines on the market and describe the development of new live vaccines with a focus on attenuated bacteria and food-related lactic acid bacteria. Furthermore, we outline the safety concerns and identify the hazards associated with live bacterial vaccines and try to give some suggestions of what to consider during their development.",2006 Jun 23,"['Detmer, Ann', 'Glenting, Jacob']",Microb Cell Fact,,,True
78326020e9f7cd75415a3a192729ccf0c0930281,PMC,Association of SARS susceptibility with single nucleic acid polymorphisms of OAS1 and MxA genes: a case-control study,http://dx.doi.org/10.1186/1471-2334-6-106,PMC1550407,16824203,CC BY,"BACKGROUND: Host genetic factors may play a role in susceptibility and resistance to SARS associated coronavirus (SARS-CoV) infection. The study was carried out to investigate the association between the genetic polymorphisms of 2',5'-oligoadenylate synthetase 1 (OAS1) gene as well as myxovirus resistance 1 (MxA) gene and susceptibility to SARS in Chinese Han population. METHODS: A hospital-based case-control study was conducted. A collective of 66 SARS cases and 64 close contact uninfected controls were enrolled in this study. End point real time polymerase chain reaction (PCR) and PCR-based Restriction Fragment Length Polymorphism (RFLP) analysis were used to detect the single nucleic polymorphisms (SNPs) in OAS1 and MxA genes. Information on other factors associated with SARS infection was collected using a pre-tested questionnaire. Univariate and multivariate logistic analyses were conducted. RESULTS: One polymorphism in the 3'-untranslated region (3'-UTR) of the OAS1 gene was associated with SARS infection. Compared to AA genotype, AG and GG genotypes were found associated with a protective effect on SARS infection with ORs (95% CI) of 0.42 (0.20~0.89) and 0.30 (0.09~0.97), respectively. Also, a GT genotype at position 88 in the MxA gene promoter was associated with increased susceptibility to SARS infection compared to a GG genotype (OR = 3.06, 95% CI: 1.25~7.50). The associations of AG genotype in OAS1 and GT genotype in MxA remained significant in multivariate analyses after adjusting for SARS protective measures (OR = 0.38, 95% CI: 0.14~0.98 and OR = 3.22, 95% CI: 1.13~9.18, respectively). CONCLUSION: SNPs in the OAS1 3'-UTR and MxA promoter region appear associated with host susceptibility to SARS in Chinese Han population.",2006 Jul 6,"['He, Jing', 'Feng, Dan', 'de Vlas, Sake J', 'Wang, Hongwei', 'Fontanet, Arnaud', 'Zhang, Panhe', 'Plancoulaine, Sabine', 'Tang, Fang', 'Zhan, Lin', 'Yang, Hong', 'Wang, Tianbao', 'Richardus, Jan H', 'Habbema, J Dik F', 'Cao, Wuchun']",BMC Infect Dis,,,True
976dd497031581e697cbf2d98042f7c184e9fb40,PMC,Frequent detection of bocavirus DNA in German children with respiratory tract infections,http://dx.doi.org/10.1186/1471-2334-6-109,PMC1550408,16834781,CC BY,"BACKGROUND: In a substantial proportion of respiratory tract diseases of suspected infectious origin, the etiology is unknown. Some of these cases may be caused by the recently described human bocavirus (hBoV). The aim of this study was to investigate the frequency and the potential clinical relevance of hBoV in pediatric patients. METHODS: We tested 835 nasopharyngeal aspirates (NPA) obtained between 2002 and 2005 from pediatric in-patients with acute respiratory tract diseases at the University of Würzburg, Germany, for the presence of hBoV DNA. The specificity of positive PCR reactions was confirmed by sequencing. RESULTS: HBoV DNA was found in 87 (10.3 %) of the NPAs. The median age of the infants and children with hBoV infection was 1.8 years (mean age 2.0 years; range 18 days – 8 years). Infections with hBoV were found year-round, though most occurred in the winter months. Coinfections were found in 34 (39.1 %) of the hBoV positive samples. RSV, influenza A, and adenoviruses were most frequently detected as coinfecting agents. Sequence determination of the PCR products in the NP-1 region revealed high identity (99 %) between the nucleotide sequences obtained in different years and in comparison to the Swedish viruses ST1 and ST2. An association of hBoV with a distinct respiratory tract manifestation was not apparent. CONCLUSION: HBoV is frequently found in NPAs of hospitalized infants and children with acute respiratory tract diseases. Proving the clinical relevance of hBoV is challenging, because application of some of Koch's revised postulates is not possible. Because of the high rate of coinfections with hBoV and other respiratory tract pathogens, an association between hBoV and respiratory tract diseases remains unproven.",2006 Jul 11,"['Weissbrich, Benedikt', 'Neske, Florian', 'Schubert, Jörg', 'Tollmann, Franz', 'Blath, Katharina', 'Blessing, Kerstin', 'Kreth, Hans Wolfgang']",BMC Infect Dis,,,True
31d83e6ac0ab75190caaa5d5bcbb2fb745fc98cc,PMC,What Internet Services Would Patients Like From Hospitals During an Epidemic? Lessons From the SARS Outbreak in Toronto,http://dx.doi.org/10.2196/jmir.7.4.e46,PMC1550678,16236698,CC BY,"BACKGROUND: International health organizations and officials are bracing for a pandemic. Although the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto did not reach such a level, it created a unique opportunity to identify the optimal use of the Internet to promote communication with the public and to preserve health services during an epidemic. OBJECTIVE: The aim of the study was to explore patients’ attitudes regarding the health services that might be provided through the Internet to supplement those traditionally available in the event of a future mass emergency situation. METHODS: We conducted “mask-to-mask” surveys of patients at three major teaching hospitals in Toronto during the second outbreak of SARS. Patients were surveyed at the hospital entrances and selected clinics. Descriptive statistics and logistic regression models were used for the analysis. RESULTS: In total, 1019 of 1130 patients responded to the survey (90% overall response rate). With respect to Internet use, 70% (711/1019) used the Internet by themselves and 57% (578/1019) with the help of a friend or family member. Of the Internet users, 68% (485/711) had already searched the World Wide Web for health information, and 75% (533/711) were interested in communicating with health professionals using the Internet as part of their ongoing care. Internet users expressed interest in using the Web for the following reasons: to learn about their health condition through patient education materials (84%), to obtain information about the status of their clinic appointments (83%), to send feedback to the hospital about how to improve its services (77%), to access screening tools to help determine if they were potentially affected by the infectious agent responsible for the outbreak (77%), to renew prescriptions (75%), to consult with their health professional about nonurgent matters (75%), and to access laboratory test results (75%). Regression results showed that younger age, higher education, and English as a first language were predictors of patients’ interest in using Internet services in the event of an epidemic. CONCLUSION: Most patients are willing and able to use the Internet as a means to maintain communication with the hospital during an outbreak of an infectious disease such as SARS. Hospitals should explore new ways to interact with the public, to provide relevant health information, and to ensure continuity of care when they are forced to restrict their services.",2005 Aug 3,"['Rizo, Carlos A', 'Lupea, Doina', 'Baybourdy, Homayoun', 'Anderson, Matthew', 'Closson, Tom', 'Jadad, Alejandro R']",J Med Internet Res,,,False
bcaf2f13566d01650664af7ef4f8a3a9aa6b2b71,PMC,What Internet Services Would Patients Like From Hospitals During an Epidemic? Lessons From the SARS Outbreak in Toronto,http://dx.doi.org/10.2196/jmir.7.4.e46,PMC1550678,16236698,CC BY,"BACKGROUND: International health organizations and officials are bracing for a pandemic. Although the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto did not reach such a level, it created a unique opportunity to identify the optimal use of the Internet to promote communication with the public and to preserve health services during an epidemic. OBJECTIVE: The aim of the study was to explore patients’ attitudes regarding the health services that might be provided through the Internet to supplement those traditionally available in the event of a future mass emergency situation. METHODS: We conducted “mask-to-mask” surveys of patients at three major teaching hospitals in Toronto during the second outbreak of SARS. Patients were surveyed at the hospital entrances and selected clinics. Descriptive statistics and logistic regression models were used for the analysis. RESULTS: In total, 1019 of 1130 patients responded to the survey (90% overall response rate). With respect to Internet use, 70% (711/1019) used the Internet by themselves and 57% (578/1019) with the help of a friend or family member. Of the Internet users, 68% (485/711) had already searched the World Wide Web for health information, and 75% (533/711) were interested in communicating with health professionals using the Internet as part of their ongoing care. Internet users expressed interest in using the Web for the following reasons: to learn about their health condition through patient education materials (84%), to obtain information about the status of their clinic appointments (83%), to send feedback to the hospital about how to improve its services (77%), to access screening tools to help determine if they were potentially affected by the infectious agent responsible for the outbreak (77%), to renew prescriptions (75%), to consult with their health professional about nonurgent matters (75%), and to access laboratory test results (75%). Regression results showed that younger age, higher education, and English as a first language were predictors of patients’ interest in using Internet services in the event of an epidemic. CONCLUSION: Most patients are willing and able to use the Internet as a means to maintain communication with the hospital during an outbreak of an infectious disease such as SARS. Hospitals should explore new ways to interact with the public, to provide relevant health information, and to ensure continuity of care when they are forced to restrict their services.",2005 Aug 3,"['Rizo, Carlos A', 'Lupea, Doina', 'Baybourdy, Homayoun', 'Anderson, Matthew', 'Closson, Tom', 'Jadad, Alejandro R']",J Med Internet Res,,,False
aecd12a815bf5fd6486b92bc8fb631d00fef541f,PMC,Using simulation for training and to change protocol during the outbreak of severe acute respiratory syndrome,http://dx.doi.org/10.1186/cc3916,PMC1550819,16356209,CC BY,"INTRODUCTION: During the 2003 severe acute respiratory syndrome (SARS) crisis, we proposed and tested a new protocol for cardiac arrest in a patient with SARS. The protocol was rapidly and effectively instituted by teamwork training using high-fidelity simulation. METHODS: Phase 1 was a curriculum design of a SARS-specific cardiac arrest protocol in three steps: planning the new protocol, repeated simulations of this protocol in a classroom, and a subsequent simulation of a cardiac arrest on a hospital ward. Phase 2 was the training of 275 healthcare workers (HCWs) using the new protocol. Training involved a seminar, practice in wearing the mandatory personal protection system (PPS), and cardiac arrest simulations with subsequent debriefing. RESULTS: Simulation provided insights that had not been considered in earlier phases of development. For example, a single person can don a PPS worn for the SARS patient in 1 1/2 minutes. However, when multiple members of a cardiac arrest team were dressing simultaneously, the time to don the PPS increased to between 3 1/2 and 5 1/2 minutes. Errors in infection control as well as in medical management of advanced cardiac life support (ACLS) were corrected. CONCLUSION: During the SARS crisis, real-time use of a high-fidelity simulator allowed the training of 275 HCWs in 2 weeks, with debriefing and error management. HCWs were required to manage the SARS cardiac arrest wearing unfamiliar equipment and following a modified ACLS protocol. The insight gained from this experience will be valuable for future infectious disease challenges in critical care.",2006 Nov 24,"['Abrahamson, Simon D', 'Canzian, Sonya', 'Brunet, Fabrice']",Crit Care,,,True
5afe948e33645324e3fb0fe4e4d27b1bba317364,PMC,Diagnostic value of real-time polymerase chain reaction to detect viruses in young children admitted to the paediatric intensive care unit with lower respiratory tract infection,http://dx.doi.org/10.1186/cc4895,PMC1550925,16611370,CC BY,"INTRODUCTION: The aetiology of lower respiratory tract infections in young children admitted to the paediatric intensive care unit (PICU) is often difficult to establish. However, most infections are believed to be caused by respiratory viruses. A diagnostic study was performed to compare conventional viral tests with the recently developed real-time PCR technique. METHOD: Samples from children aged under 5 years presenting to a tertiary PICU suspected of having a lower respiratory tract infection were tested using conventional methods (viral culture and immunofluorescence) and real-time PCR during the winter season from December 2004 to May 2005. Conventional methods were used to check for respiratory syncytial virus, influenzavirus, parainfluenzavirus 1–3, rhinoviruses and adenoviruses. Real-time PCR was used to test for respiratory syncytial virus, influenzavirus, parainfluenzavirus 1–4, rhinoviruses, adenoviruses, human coronaviruses OC43, NL63 and 229E, human metapneumovirus, Mycoplasma pneumoniae and Chlamydia pneumoniae. RESULTS: A total of 23 patients were included, of whom 11 (48%) were positive for a respiratory virus by conventional methods. Real-time PCR confirmed all of these positive results. In addition, real-time PCR identified 22 more viruses in 11 patients, yielding a total of 22 (96%) patients with a positive sample. More than one virus was detected in eight (35%) children. CONCLUSION: Real-time PCR for respiratory viruses was found to be a sensitive and reliable method in PICU patients with lower respiratory tract infection, increasing the diagnostic yield twofold compared to conventional methods.",2006 Apr 12,"['van de Pol, Alma C', 'Wolfs, Tom FW', 'Jansen, Nicolaas JG', 'van Loon, Anton M', 'Rossen, John WA']",Crit Care,,,True
4c84dbfd01f7b2009ebed54376da8afcbcf1ec64,PMC,Model-Based Design of Growth-Attenuated Viruses,http://dx.doi.org/10.1371/journal.pcbi.0020116,PMC1557587,16948530,CC BY,"Live-virus vaccines activate both humoral and cell-mediated immunity, require only a single boosting, and generally provide longer immune protection than killed or subunit vaccines. However, growth of live-virus vaccines must be attenuated to minimize their potential pathogenic effects, and mechanisms of attenuation by conventional serial-transfer viral adaptation are not well-understood. New methods of attenuation based on rational engineering of viral genomes may offer a potentially greater control if one can link defined genetic modifications to changes in virus growth. To begin to establish such links between genotype and growth phenotype, we developed a computer model for the intracellular growth of vesicular stomatitis virus (VSV), a well-studied, nonsegmented, negative-stranded RNA virus. Our model incorporated established regulatory mechanisms of VSV while integrating key wild-type infection steps: hijacking of host resources, transcription, translation, and replication, followed by assembly and release of progeny VSV particles. Generalization of the wild-type model to allow for genome rearrangements matched the experimentally observed attenuation ranking for recombinant VSV strains that altered the genome position of their nucleocapsid gene. Finally, our simulations captured previously reported experimental results showing how altering the positions of other VSV genes has the potential to attenuate the VSV growth while overexpressing the immunogenic VSV surface glycoprotein. Such models will facilitate the engineering of new live-virus vaccines by linking genomic manipulations to controlled changes in virus gene-expression and growth.",2006 Sep 1,"['Lim, Kwang-il', 'Lang, Tobias', 'Lam, Vy', 'Yin, John']",PLoS Comput Biol,,,True
6c6ac6629c8a603c01953ae37469014700102ed8,PMC,Hospice utilization during the SARS outbreak in Taiwan,http://dx.doi.org/10.1186/1472-6963-6-94,PMC1559606,16889656,CC BY,"BACKGROUND: The severe acute respiratory syndrome (SARS) epidemic threw the world into turmoil during the first half of 2003. Many subsequent papers have addressed its impact on health service utilization, but few have considered palliative (hospice) care. The aim of the present study was to describe changes in hospice inpatient utilization during and after the SARS epidemic in 2003 in Taiwan. METHODS: The data sources were the complete datasets of inpatient admissions during 2002 and 2003 from the National Health Insurance Research Database. Before-and-after comparisons of daily and monthly utilizations were made. Hospice analyses were limited to those wards that offered inpatient services throughout these two years. The comparisons were extended to total hospital bed utilization and to patients who were still admitted to hospice wards during the peak period of the SARS epidemic. RESULTS: Only 15 hospice wards operated throughout the whole of 2002 and 2003. In 2003, hospice utilization began to decrease in the middle of April, reached a minimum on 25 May, and gradually recovered to the level of the previous November. Hospices showed a more marked reduction in utilization than all hospital beds (e.g. -52.5% vs. -19.9% in May 2003) and a slower recovery with a three-month lag. In total, 566 patients were admitted to hospice wards in May/June 2003, in contrast to 818 in May/June 2002. Gender, age and diagnosis distributions did not differ. CONCLUSION: Hospice inpatient utilization in Taiwan was indeed more sensitive to the emerging epidemic than general inpatient utilization. A well-balanced network with seamless continuity of care should be ensured.",2006 Aug 4,"['Chen, Tzeng-Ji', 'Lin, Ming-Hwai', 'Chou, Li-Fang', 'Hwang, Shinn-Jang']",BMC Health Serv Res,,,True
5faef288fa2cd3e02a6d12b9e09912decde1032c,PMC,"Ethnoveterinary medicines used for horses in Trinidad and in British Columbia, Canada",http://dx.doi.org/10.1186/1746-4269-2-31,PMC1559680,16893454,CC BY,"This paper investigates the commonalities in ethnoveterinary medicine used for horses between Trinidad (West Indies) and British Columbia (Canada). These research areas are part of a common market in pharmaceuticals and are both involved in the North American racing circuit. There has been very little research conducted on medicinal plants used for horses although their use is widespread. The data on ethnoveterinary medicines used for horses was obtained through key informant interviews with horse owners, trainers, breeders, jockeys, grooms and animal care specialists in two research areas: Trinidad and British Columbia (BC). A participatory validation workshop was held in BC. An extensive literature review and botanical identification of the plants was also done. In all, 20 plants were found to be used in treating racehorses in Trinidad and 97 in BC. Of these the most-evidently effective plants 19 of the plants used in Trinidad and 66 of those used in BC are described and evaluated in this paper. Aloe vera, Curcuma longa and Ricinus communis are used in both research areas. More research is needed in Trinidad to identify plants that respondents claimed were used in the past. Far more studies have been conducted on the temperate and Chinese medicinal plants used in BC and therefore these ethnoveterinary remedies reflect stronger evidence of efficacy.",2006 Aug 7,"['Lans, Cheryl', 'Turner, Nancy', 'Brauer, Gerhard', 'Lourenco, Grant', 'Georges, Karla']",J Ethnobiol Ethnomed,,,True
275d7a25357ea46699072167d4ca109108132068,PMC,Surveillance recommendations based on an exploratory analysis of respiratory syncytial virus reports derived from the European Influenza Surveillance System,http://dx.doi.org/10.1186/1471-2334-6-128,PMC1560143,16899110,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is an important pathogen that can cause severe illness in infants and young children. In this study, we assessed whether data on RSV collected by the European Influenza Surveillance Scheme (EISS) could be used to build an RSV surveillance system in Europe. METHODS: Influenza and RSV data for the 2002–2003 winter season were analysed for England, France, the Netherlands and Scotland. Data from sentinel physician networks and other sources, mainly hospitals, were collected. Respiratory specimens were tested for influenza and RSV mainly by virus culture and polymerase chain reaction amplification. RESULTS: Data on RSV were entered timely into the EISS database. RSV contributed noticeably to influenza-like illness: in England sentinel RSV detections were common in all age groups, but particularly in young children with 20 (40.8%) of the total number of sentinel swabs testing positive for RSV. Scotland and France also reported the highest percentages of RSV detections in the 0–4 year age group, respectively 10.3% (N = 29) and 12.2% (N = 426). In the Netherlands, RSV was detected in one person aged over 65 years. CONCLUSION: We recommend that respiratory specimens collected in influenza surveillance are also tested systematically for RSV and emphasize the use of both community derived data and data from hospitals for RSV surveillance. RSV data from the EISS have been entered in a timely manner and we consider that the EISS model can be used to develop an RSV surveillance system equivalent to the influenza surveillance in Europe.",2006 Aug 9,"['Meerhoff, Tamara J', 'Fleming, Douglas', 'Smith, Ann', 'Mosnier, Anne', 'van Gageldonk-Lafeber, Arianne B', 'Paget, W John', None]",BMC Infect Dis,,,True
8bcd86c97a06dbdff096f6cb164f9dab35f879f9,PMC,"Factors associated with nosocomial SARS-CoV transmission among healthcare workers in Hanoi, Vietnam, 2003",http://dx.doi.org/10.1186/1471-2458-6-207,PMC1562405,16907978,CC BY,"BACKGROUND: In March of 2003, an outbreak of Severe Acute Respiratory Syndrome (SARS) occurred in Northern Vietnam. This outbreak began when a traveler arriving from Hong Kong sought medical care at a small hospital (Hospital A) in Hanoi, initiating a serious and substantial transmission event within the hospital, and subsequent limited spread within the community. METHODS: We surveyed Hospital A personnel for exposure to the index patient and for symptoms of disease during the outbreak. Additionally, serum specimens were collected and assayed for antibody to SARS-associated coronavirus (SARS-CoV) antibody and job-specific attack rates were calculated. A nested case-control analysis was performed to assess risk factors for acquiring SARS-CoV infection. RESULTS: One hundred and fifty-three of 193 (79.3%) clinical and non-clinical staff consented to participate. Excluding job categories with <3 workers, the highest SARS attack rates occurred among nurses who worked in the outpatient and inpatient general wards (57.1, 47.4%, respectively). Nurses assigned to the operating room/intensive care unit, experienced the lowest attack rates (7.1%) among all clinical staff. Serologic evidence of SARS-CoV infection was detected in 4 individuals, including 2 non-clinical workers, who had not previously been identified as SARS cases; none reported having had fever or cough. Entering the index patient's room and having seen (viewed) the patient were the behaviors associated with highest risk for infection by univariate analysis (odds ratios 20.0, 14.0; 95% confidence intervals 4.1–97.1, 3.6–55.3, respectively). CONCLUSION: This study highlights job categories and activities associated with increased risk for SARS-CoV infection and demonstrates that a broad diversity of hospital workers may be vulnerable during an outbreak. These findings may help guide recommendations for the protection of vulnerable occupational groups and may have implications for other respiratory infections such as influenza.",2006 Aug 14,"['Reynolds, Mary G', 'Anh, Bach Huy', 'Thu, Vu Hoang', 'Montgomery, Joel M', 'Bausch, Daniel G', 'Shah, J Jina', 'Maloney, Susan', 'Leitmeyer, Katrin C', 'Huy, Vu Quang', 'Horby, Peter', 'Plant, Aileen Y', 'Uyeki, Timothy M']",BMC Public Health,,,True
d665907080d2eae92859eab542dce90a57f11efb,PMC,Mixing patterns and the spread of close-contact infectious diseases,http://dx.doi.org/10.1186/1742-7622-3-10,PMC1562421,16907980,CC BY,"Surprisingly little is known regarding the human mixing patterns relevant to the spread of close-contact infections, such as measles, influenza and meningococcal disease. This study aims to estimate the number of partnerships that individuals make, their stability and the degree to which mixing is assortative with respect to age. We defined four levels of putative at-risk events from casual (physical contact without conversation) to intimate (contact of a sexual nature), and asked university student volunteers to record details on those they contacted at these levels on three separate days. We found that intimate contacts are stable over short time periods whereas there was no evidence of repeat casual contacts with the same individuals. The contacts were increasingly assortative as intimacy increased. Such information will aid the development and parameterisation of models of close contact diseases, and may have direct use in outbreak investigations.",2006 Aug 14,"['Edmunds, WJ', 'Kafatos, G', 'Wallinga, J', 'Mossong, JR']",Emerg Themes Epidemiol,,,True
3ebb8d173e6297001673ec3ce3bb14e5c1cb9715,PMC,Caveolin-1 and -2 in airway epithelium: expression and in situ association as detected by FRET-CLSM,http://dx.doi.org/10.1186/1465-9921-7-108,PMC1563466,16904002,CC BY,"BACKGROUND: Caveolae are involved in diverse cellular functions such as signal transduction, cholesterol homeostasis, endo- and transcytosis, and also may serve as entry sites for microorganisms. Hence, their occurrence in epithelium of the airways might be expected but, nonetheless, has not yet been examined. METHODS: Western blotting, real-time quantitative PCR analysis of abraded tracheal epithelium and laser-assisted microdissection combined with subsequent mRNA analysis were used to examine the expression of cav-1 and cav-2, two major caveolar coat proteins, in rat tracheal epithelium. Fluorescence immunohistochemistry was performed to locate caveolae and cav-1 and -2 in the airway epithelium of rats, mice and humans. Electron-microscopic analysis was used for the identification of caveolae. CLSM-FRET analysis determined the interaction of cav-1α and cav-2 in situ. RESULTS: Western blotting and laser-assisted microdissection identified protein and transcripts, respectively, of cav-1 and cav-2 in airway epithelium. Real-time quantitative RT-PCR analysis of abraded tracheal epithelium revealed a higher expression of cav-2 than of cav-1. Immunoreactivities for cav-1 and for cav-2 were co-localized in the cell membrane of the basal cells and basolaterally in the ciliated epithelial cells of large airways of rat and human. However, no labeling for cav-1 or cav-2 was observed in the epithelial cells of small bronchi. Using conventional double-labeling indirect immunofluorescence combined with CLSM-FRET analysis, we detected an association of cav-1α and -2 in epithelial cells. The presence of caveolae was confirmed by electron microscopy. In contrast to human and rat, cav-1-immunoreactivity and caveolae were confined to basal cells in mice. Epithelial caveolae were absent in cav-1-deficient mice, implicating a requirement of this caveolar protein in epithelial caveolae formation. CONCLUSION: These results show that caveolae and caveolins are integral membrane components in basal and ciliated epithelial cells, indicating a crucial role in these cell types. In addition to their physiological role, they may be involved in airway infection.",2006 Aug 11,"['Krasteva, Gabriela', 'Pfeil, Uwe', 'Drab, Marek', 'Kummer, Wolfgang', 'König, Peter']",Respir Res,,,True
968aa40cb4dd0cab313ecc59ff2f85800cbc1b8b,PMC,Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcεRI-aggregation reveals a complex network of genes involved in inflammatory responses,http://dx.doi.org/10.1186/1471-2164-7-210,PMC1564015,16911805,CC BY,"BACKGROUND: Mast cells are well established effectors of IgE-triggered allergic reactions and immune responses to parasitic infections. Recent studies indicate that mast cells may play roles in adaptive and innate immunity, suggesting an innovative view of the regulation of immune responses. Here, we profiled the transcriptome of human mast cells sensitized with IgE alone, or stimulated by FcεRI aggregation. RESULTS: Our data show that among 8,793 genes examined, 559 genes are differentially regulated in stimulated mast cells when compared with resting/unstimulated mast cells. The major functional categories of upregulated genes include cytokines, chemokines, and other genes involved in innate and adaptive immune-responses. We observed the increased expression of over 63 gene-transcripts following IgE-sensitization alone. Our data was validated using Real-Time-PCR; ELISA and western blot. We confirmed that IgE alone does not trigger mast cell-immediate responses, such as calcium signals, degranulation or protein-phosphorylation. CONCLUSION: This report represents a substantial advance in our understanding of the genome wide effects triggered by ""passive sensitization"" or active stimulation of human mast cells, supporting mast cells' potential involvement in a wide range of inflammatory responses.",2006 Aug 16,"['Jayapal, Manikandan', 'Tay, Hwee Kee', 'Reghunathan, Renji', 'Zhi, Liang', 'Chow, Kah Kiong', 'Rauff, Mary', 'Melendez, Alirio J']",BMC Genomics,,,True
2884fdee6db20fa38c7ad56008b0ff4b84eeb41d,PMC,How long do nosocomial pathogens persist on inanimate surfaces? A systematic review,http://dx.doi.org/10.1186/1471-2334-6-130,PMC1564025,16914034,CC BY,"BACKGROUND: Inanimate surfaces have often been described as the source for outbreaks of nosocomial infections. The aim of this review is to summarize data on the persistence of different nosocomial pathogens on inanimate surfaces. METHODS: The literature was systematically reviewed in MedLine without language restrictions. In addition, cited articles in a report were assessed and standard textbooks on the topic were reviewed. All reports with experimental evidence on the duration of persistence of a nosocomial pathogen on any type of surface were included. RESULTS: Most gram-positive bacteria, such as Enterococcus spp. (including VRE), Staphylococcus aureus (including MRSA), or Streptococcus pyogenes, survive for months on dry surfaces. Many gram-negative species, such as Acinetobacter spp., Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia marcescens, or Shigella spp., can also survive for months. A few others, such as Bordetella pertussis, Haemophilus influenzae, Proteus vulgaris, or Vibrio cholerae, however, persist only for days. Mycobacteria, including Mycobacterium tuberculosis, and spore-forming bacteria, including Clostridium difficile, can also survive for months on surfaces. Candida albicans as the most important nosocomial fungal pathogen can survive up to 4 months on surfaces. Persistence of other yeasts, such as Torulopsis glabrata, was described to be similar (5 months) or shorter (Candida parapsilosis, 14 days). Most viruses from the respiratory tract, such as corona, coxsackie, influenza, SARS or rhino virus, can persist on surfaces for a few days. Viruses from the gastrointestinal tract, such as astrovirus, HAV, polio- or rota virus, persist for approximately 2 months. Blood-borne viruses, such as HBV or HIV, can persist for more than one week. Herpes viruses, such as CMV or HSV type 1 and 2, have been shown to persist from only a few hours up to 7 days. CONCLUSION: The most common nosocomial pathogens may well survive or persist on surfaces for months and can thereby be a continuous source of transmission if no regular preventive surface disinfection is performed.",2006 Aug 16,"['Kramer, Axel', 'Schwebke, Ingeborg', 'Kampf, Günter']",BMC Infect Dis,,,True
5dc0b8b662824323881c3a1ae3a1bae2a821484d,PMC,SARS: Systematic Review of Treatment Effects,http://dx.doi.org/10.1371/journal.pmed.0030343,PMC1564166,16968120,CC0,"BACKGROUND: The SARS outbreak of 2002–2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO) expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. METHODS AND FINDINGS: In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. CONCLUSIONS: Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage and timing, and to accrue data in real time during future outbreaks to monitor specific adverse effects and help inform treatment.",2006 Sep 12,"['Stockman, Lauren J', 'Bellamy, Richard', 'Garner, Paul']",PLoS Med,,,True
7de21b4df4bb390e0fba8c0938ef6eeef9a4630e,PMC,A New Arthritis Therapy with Oxidative Burst Inducers,http://dx.doi.org/10.1371/journal.pmed.0030348,PMC1564167,16968121,CC BY,"BACKGROUND: Despite recent successes with biological agents as therapy for autoimmune inflammatory diseases such as rheumatoid arthritis (RA), many patients fail to respond adequately to these treatments, making a continued search for new therapies extremely important. Recently, the prevailing hypothesis that reactive oxygen species (ROS) promote inflammation was challenged when polymorphisms in Ncf1, that decrease oxidative burst, were shown to increase disease severity in mouse and rat arthritis models. Based on these findings we developed a new therapy for arthritis using oxidative burst-inducing substances. METHODS AND FINDINGS: Treatment of rats with phytol (3,7,11,15-tetramethyl-2-hexadecene-1-ol) increased oxidative burst in vivo and thereby corrected the effect of the genetic polymorphism in arthritis-prone Ncf1 (DA) rats. Importantly, phytol treatment also decreased the autoimmune response and ameliorated both the acute and chronic phases of arthritis. When compared to standard therapies for RA, anti-tumour necrosis factor-α and methotrexate, phytol showed equally good or better therapeutic properties. Finally, phytol mediated its effect within hours of administration and involved modulation of T cell activation, as injection prevented adoptive transfer of disease with arthritogenic T cells. CONCLUSIONS: Treatment of arthritis with ROS-promoting substances such as phytol targets a newly discovered pathway leading to autoimmune inflammatory disease and introduces a novel class of therapeutics for treatment of RA and possibly other chronic inflammatory diseases.",2006 Sep 12,"['Hultqvist, Malin', 'Olofsson, Peter', 'Gelderman, Kyra A', 'Holmberg, Jens', 'Holmdahl, Rikard']",PLoS Med,,,True
381f1d10b47e89d45a1008b53292c66c034b6960,PMC,Empirical Evidence for the Effect of Airline Travel on Inter-Regional Influenza Spread in the United States,http://dx.doi.org/10.1371/journal.pmed.0030401,PMC1564183,16968115,CC BY,"BACKGROUND: The influence of air travel on influenza spread has been the subject of numerous investigations using simulation, but very little empirical evidence has been provided. Understanding the role of airline travel in large-scale influenza spread is especially important given the mounting threat of an influenza pandemic. Several recent simulation studies have concluded that air travel restrictions may not have a significant impact on the course of a pandemic. Here, we assess, with empirical data, the role of airline volume on the yearly inter-regional spread of influenza in the United States. METHODS AND FINDINGS: We measured rate of inter-regional spread and timing of influenza in the United States for nine seasons, from 1996 to 2005 using weekly influenza and pneumonia mortality from the Centers for Disease Control and Prevention. Seasonality was characterized by band-pass filtering. We found that domestic airline travel volume in November (mostly surrounding the Thanksgiving holiday) predicts the rate of influenza spread (r (2) = 0.60; p = 0.014). We also found that international airline travel influences the timing of influenza mortality (r (2) = 0.59; p = 0.016). The flight ban in the US after the terrorist attack on September 11, 2001, and the subsequent depression of the air travel market, provided a natural experiment for the evaluation of flight restrictions; the decrease in air travel was associated with a delayed and prolonged influenza season. CONCLUSIONS: We provide the first empirical evidence for the role of airline travel in long-range dissemination of influenza. Our results suggest an important influence of international air travel on the timing of influenza introduction, as well as an influence of domestic air travel on the rate of inter-regional influenza spread in the US. Pandemic preparedness strategies should account for a possible benefit of airline travel restrictions on influenza spread.",2006 Oct 12,"['Brownstein, John S', 'Wolfe, Cecily J', 'Mandl, Kenneth D']",PLoS Med,,,True
cdffc1eadb85e776433b6850a2dd40a350874622,PMC,Natural products that reduce rotavirus infectivity identified by a cell-based moderate-throughput screening assay,http://dx.doi.org/10.1186/1743-422X-3-68,PMC1564392,16948846,CC BY,"BACKGROUND: There is widespread interest in the use of innate immune modulators as a defense strategy against infectious pathogens. Using rotavirus as a model system, we developed a cell-based, moderate-throughput screening (MTS) assay to identify compounds that reduce rotavirus infectivity in vitro, toward a long-term goal of discovering immunomodulatory agents that enhance innate responses to viral infection. RESULTS: A natural product library consisting of 280 compounds was screened in the assay and 15 compounds that significantly reduced infectivity without cytotoxicity were identified. Time course analysis of four compounds with previously characterized effects on inflammatory gene expression inhibited replication with pre-treatment times as minimal as 2 hours. Two of these four compounds, α-mangostin and 18-β-glycyrrhetinic acid, activated NFκB and induced IL-8 secretion. The assay is adaptable to other virus systems, and amenable to full automation and adaptation to a high-throughput format. CONCLUSION: Identification of several compounds with known effects on inflammatory and antiviral gene expression that confer resistance to rotavirus infection in vitro suggests the assay is an appropriate platform for discovery of compounds with potential to amplify innate antiviral responses.",2006 Sep 1,"['Shaneyfelt, Mark E', 'Burke, Anna D', 'Graff, Joel W', 'Jutila, Mark A', 'Hardy, Michele E']",Virol J,,,True
c6183dfbaabc06881c70097745b3e646479ac9a7,PMC,Climate Change and Human Health Impacts in the United States: An Update on the Results of the U.S. National Assessment,http://dx.doi.org/10.1289/ehp.8880,PMC1570072,16966082,CC0,"The health sector component of the first U.S. National Assessment, published in 2000, synthesized the anticipated health impacts of climate variability and change for five categories of health outcomes: impacts attributable to temperature, extreme weather events (e.g., storms and floods), air pollution, water- and food-borne diseases, and vector- and rodent-borne diseases. The Health Sector Assessment (HSA) concluded that climate variability and change are likely to increase morbidity and mortality risks for several climate-sensitive health outcomes, with the net impact uncertain. The objective of this study was to update the first HSA based on recent publications that address the potential impacts of climate variability and change in the United States for the five health outcome categories. The literature published since the first HSA supports the initial conclusions, with new data refining quantitative exposure–response relationships for several health end points, particularly for extreme heat events and air pollution. The United States continues to have a very high capacity to plan for and respond to climate change, although relatively little progress has been noted in the literature on implementing adaptive strategies and measures. Large knowledge gaps remain, resulting in a substantial need for additional research to improve our understanding of how weather and climate, both directly and indirectly, can influence human health. Filling these knowledge gaps will help better define the potential health impacts of climate change and identify specific public health adaptations to increase resilience.",2006 Sep 18,"['Ebi, Kristie L.', 'Mills, David M.', 'Smith, Joel B.', 'Grambsch, Anne']",Environ Health Perspect,,,True
7bb628111d2f63d10959355b1102887abeed0f44,PMC,Are Nonhuman Primates Good Models for SARS?,http://dx.doi.org/10.1371/journal.pmed.0030411,PMC1576335,17002511,CC BY,,2006 Sep 26,"Hogan, Robert J",PLoS Med,,,True
e1e11bdec2d27ec0b9675e684fc2653513a029bd,PMC,Authors' Response to Hogan,http://dx.doi.org/10.1371/journal.pmed.0030415,PMC1576339,,CC BY,,2006 Sep 26,"['Haagmans, Bart L', 'Osterhaus, Albert D. M. E']",PLoS Med,,,True
acc751e3f39515573231c168c3c530bfff91fee6,PMC,S1 gene sequence analysis of a nephropathogenic strain of avian infectious bronchitis virus in Egypt,http://dx.doi.org/10.1186/1743-422X-3-78,PMC1592083,16987422,CC BY,"BACKGROUND: Infectious bronchitis is highly contagious and constitutes one of the most common and difficult poultry diseases to control. IBV is endemic in probably all countries that raise chickens. It exists as dozens of serotypes/genotypes. Only a few amino acid differences in the S1 protein of vaccine and challenge strains of IBV may result in poor protection. Tropism of IBV includes the respiratory tract tissues, proventriculus and caecal tonsils of the alimentary tract, the oviduct and the kidney. RESULTS: Infectious bronchitis virus (IBV) strain closely related to Massachusetts (Mass) serotype was isolated from broiler chickens suffering from severe renal and respiratory distresses. The isolate was serologically identified by Dot-ELISA and further characterized by RT-PCR then genotyped using S1 gene sequence analysis. Alignment of the S1 sequence of the isolate with 16 IBV strains revealed high homology to isolates related to Mass serotype. Inoculation with the strain reproduced the disease in experimental 1-day-old chickens and resulted in 20% mortality, severe renal and moderate respiratory distresses. Marked histopathological changes in both kidney and trachea were observed in experimentally infected chickens. A protection study using the H120 live attenuated vaccine showed low protection rate in spite of high S1 sequence homology (97%). Protection based criteria were: virus re-isolation attempts from trachea, tracheal and renal histopathology as well as IBV antigens detection by immunofluorescent antibody technique in kidney sections. CONCLUSION: Periodical evaluation of cross-protective capabilities of IBV vaccine(s) versus recently recovered field isolates should be performed to ensure optimum control of IBV.",2006 Sep 20,"['Abdel-Moneim, Ahmed S', 'El-Kady, Magdy F', 'Ladman, Brian S', 'Gelb, Jack']",Virol J,,,True
9bf1241b4b35efdf7be808ce9bc8d44939f1e21e,PMC,Individual freedom versus collective responsibility: too many rights make a wrong?,http://dx.doi.org/10.1186/1742-7622-3-14,PMC1594563,17014728,CC BY,"Individuals might reasonably expect the freedom to make their own decisions regarding their health. However, what happens when an individual's wishes conflict with what is in that individual's best interests? How far should an individual's rights be restricted for his or her own benefit? Similarly, what limitations should be placed on an individual's behaviour when that person's wishes go against what is good for the population in general? Here we discuss the issues that can arise when the rights of individuals conflict with individual and population benefits in relation to infectious diseases.",2006 Oct 2,"['Looker, Katharine J', 'Hallett, Timothy B']",Emerg Themes Epidemiol,,,True
3e572863713d0fbe8cf60ea9991dd5c9993e6c7d,PMC,Validation of the Provincial Transfer Authorization Centre database: a comprehensive database containing records of all inter-facility patient transfers in the province of Ontario,http://dx.doi.org/10.1186/1472-6963-6-129,PMC1609112,17026763,CC BY,"BACKGROUND: The Provincial Transfer Authorization Centre (PTAC) was established as a part of the emergency response in Ontario, Canada to the Severe Acute Respiratory Syndrome (SARS) outbreak in 2003. Prior to 2003, data relating to inter-facility patient transfers were not collected in a systematic manner. Then, in an emergency setting, a comprehensive database with a complex data collection process was established. For the first time in Ontario, population-based data for patient movement between healthcare facilities for a population of twelve million are available. The PTAC database stores all patient transfer data in a large database. There are few population-based patient transfer databases and the PTAC database is believed to be the largest example to house this novel dataset. A patient transfer database has also never been validated. This paper presents the validation of the PTAC database. METHODS: A random sample of 100 patient inter-facility transfer records was compared to the corresponding institutional patient records from the sending healthcare facilities. Measures of agreement, including sensitivity, were calculated for the 12 common data variables. RESULTS: Of the 100 randomly selected patient transfer records, 95 (95%) of the corresponding institutional patient records were located. Data variables in the categories patient demographics, facility identification and timing of transfer and reason and urgency of transfer had strong agreement levels. The 10 most commonly used data variables had accuracy rates that ranged from 85.3% to 100% and error rates ranging from 0 to 12.6%. These same variables had sensitivity values ranging from 0.87 to 1.0. CONCLUSION: The very high level of agreement between institutional patient records and the PTAC data for fields compared in this study supports the validity of the PTAC database. For the first time, a population-based patient transfer database has been established. Although it was created during an emergency situation and data collection is dependent on front-line medical workers, the PTAC data has achieved a high level of validity, perhaps even higher than many purpose built databases created during non-emergency settings.",2006 Oct 6,"['Robinson, Victoria A', 'MacDonald, Russell D', 'Manuel, Doug', 'Goel, Vivek']",BMC Health Serv Res,,,True
9aa51dd5b5755afa670398027272f2e6b4f3d83b,PMC,Adaptive evolution of the spike gene of SARS coronavirus: changes in positively selected sites in different epidemic groups,http://dx.doi.org/10.1186/1471-2180-6-88,PMC1609170,17020602,CC BY,"BACKGROUND: It is believed that animal-to-human transmission of severe acute respiratory syndrome (SARS) coronavirus (CoV) is the cause of the SARS outbreak worldwide. The spike (S) protein is one of the best characterized proteins of SARS-CoV, which plays a key role in SARS-CoV overcoming species barrier and accomplishing interspecies transmission from animals to humans, suggesting that it may be the major target of selective pressure. However, the process of adaptive evolution of S protein and the exact positively selected sites associated with this process remain unknown. RESULTS: By investigating the adaptive evolution of S protein, we identified twelve amino acid sites (75, 239, 244, 311, 479, 609, 613, 743, 765, 778, 1148, and 1163) in the S protein under positive selective pressure. Based on phylogenetic tree and epidemiological investigation, SARS outbreak was divided into three epidemic groups: 02–04 interspecies, 03-early-mid, and 03-late epidemic groups in the present study. Positive selection was detected in the first two groups, which represent the course of SARS-CoV interspecies transmission and of viral adaptation to human host, respectively. In contrast, purifying selection was detected in 03-late group. These indicate that S protein experiences variable positive selective pressures before reaching stabilization. A total of 25 sites in 02–04 interspecies epidemic group and 16 sites in 03-early-mid epidemic group were identified under positive selection. The identified sites were different between these two groups except for site 239, which suggests that positively selected sites are changeable between groups. Moreover, it was showed that a larger proportion (24%) of positively selected sites was located in receptor-binding domain (RBD) than in heptad repeat (HR)1-HR2 region in 02–04 interspecies epidemic group (p = 0.0208), and a greater percentage (25%) of these sites occurred in HR1–HR2 region than in RBD in 03-early-mid epidemic group (p = 0.0721). These suggest that functionally different domains of S protein may not experience same positive selection in each epidemic group. In addition, three specific replacements (F360S, T487S and L665S) were only found between 03-human SARS-CoVs and strains from 02–04 interspecies epidemic group, which reveals that selective sweep may also force the evolution of S genes before the jump of SARS-CoVs into human hosts. Since certain residues at these positively selected sites are associated with receptor recognition and/or membrane fusion, they are likely to be the crucial residues for animal-to-human transmission of SARS-CoVs, and subsequent adaptation to human hosts. CONCLUSION: The variation of positive selective pressures and positively selected sites are likely to contribute to the adaptive evolution of S protein from animals to humans.",2006 Oct 4,"['Zhang, Chi-Yu', 'Wei, Ji-Fu', 'He, Shao-Heng']",BMC Microbiol,,,True
bdcfff55eaabeaa26d71810113d717ef85e417d1,PMC,MIMOX: a web tool for phage display based epitope mapping,http://dx.doi.org/10.1186/1471-2105-7-451,PMC1618411,17038191,CC BY,"BACKGROUND: Phage display is widely used in basic research such as the exploration of protein-protein interaction sites and networks, and applied research such as the development of new drugs, vaccines, and diagnostics. It has also become a promising method for epitope mapping. Research on new algorithms that assist and automate phage display based epitope mapping has attracted many groups. Most of the existing tools have not been implemented as an online service until now however, making it less convenient for the community to access, utilize, and evaluate them. RESULTS: We present MIMOX, a free web tool that helps to map the native epitope of an antibody based on one or more user supplied mimotopes and the antigen structure. MIMOX was coded in Perl using modules from the Bioperl project. It has two sections. In the first section, MIMOX provides a simple interface for ClustalW to align a set of mimotopes. It also provides a simple statistical method to derive the consensus sequence and embeds JalView as a Java applet to view and manage the alignment. In the second section, MIMOX can map a single mimotope or a consensus sequence of a set of mimotopes, on to the corresponding antigen structure and search for all of the clusters of residues that could represent the native epitope. NACCESS is used to evaluate the surface accessibility of the candidate clusters; and Jmol is embedded to view them interactively in their 3D context. Initial case studies show that MIMOX can reproduce mappings from existing tools such as FINDMAP and 3DEX, as well as providing novel, rational results. CONCLUSION: A web-based tool called MIMOX has been developed for phage display based epitope mapping. As a publicly available online service in this area, it is convenient for the community to access, utilize, and evaluate, complementing other existing programs. MIMOX is freely available at .",2006 Oct 12,"['Huang, Jian', 'Gutteridge, Alex', 'Honda, Wataru', 'Kanehisa, Minoru']",BMC Bioinformatics,,,True
da6d83da65e485c34b903968ae22da9efbd81628,PMC,Global response to pandemic flu: more research needed on a critical front,http://dx.doi.org/10.1186/1478-4505-4-8,PMC1618830,17038194,CC BY,"If and when sustained human-to-human transmission of H5N1 becomes a reality, the world will no longer be dealing with sporadic avian flu borne along migratory flight paths of birds, but aviation flu – winged at subsonic speed along commercial air conduits to every corner of planet Earth. Given that air transportation is the one feature that most differentiates present day transmission scenarios from those in 1918, our present inability to prevent spread of influenza by international air travel, as reckoned by the World Health Organization, constitutes a major weakness in the current global preparedness plan against pandemic flu. Despite the lessons of SARS, it is surprising that aviation-related health policy options have not been more rigorously evaluated, or scientific research aimed at strengthening public health measures on the air transportation front, more energetically pursued.",2006 Oct 13,"Lim, Meng-Kin",Health Res Policy Syst,,,True
ee1b5a9618dcc4080ed100486cedd0969e80fa4d,PMC,A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany,http://dx.doi.org/10.1186/1471-2334-6-147,PMC1618839,17026751,CC BY,"BACKGROUND: In May 2003 the Soest County Health Department was informed of an unusually large number of patients hospitalized with atypical pneumonia. METHODS: In exploratory interviews patients mentioned having visited a farmers' market where a sheep had lambed. Serologic testing confirmed the diagnosis of Q fever. We asked local health departments in Germany to identiy notified Q fever patients who had visited the farmers market. To investigate risk factors for infection we conducted a case control study (cases were Q fever patients, controls were randomly selected Soest citizens) and a cohort study among vendors at the market. The sheep exhibited at the market, the herd from which it originated as well as sheep from herds held in the vicinity of Soest were tested for Coxiella burnetii (C. burnetii). RESULTS: A total of 299 reported Q fever cases was linked to this outbreak. The mean incubation period was 21 days, with an interquartile range of 16–24 days. The case control study identified close proximity to and stopping for at least a few seconds at the sheep's pen as significant risk factors. Vendors within approximately 6 meters of the sheep's pen were at increased risk for disease compared to those located farther away. Wind played no significant role. The clinical attack rate of adults and children was estimated as 20% and 3%, respectively, 25% of cases were hospitalized. The ewe that had lambed as well as 25% of its herd tested positive for C. burnetii antibodies. CONCLUSION: Due to its size and point source nature this outbreak permitted assessment of fundamental, but seldom studied epidemiological parameters. As a consequence of this outbreak, it was recommended that pregnant sheep not be displayed in public during the 3(rd )trimester and to test animals in petting zoos regularly for C. burnetii.",2006 Oct 6,"['Porten, Klaudia', 'Rissland, Jürgen', 'Tigges, Almira', 'Broll, Susanne', 'Hopp, Wilfried', 'Lunemann, Mechthild', 'van Treeck, Ulrich', 'Kimmig, Peter', 'Brockmann, Stefan O', 'Wagner-Wiening, Christiane', 'Hellenbrand, Wiebke', 'Buchholz, Udo']",BMC Infect Dis,,,True
4b43f61d164be997a34343c11c70c42edd91898b,PMC,Distributed data processing for public health surveillance,http://dx.doi.org/10.1186/1471-2458-6-235,PMC1618842,16984658,CC BY,"BACKGROUND: Many systems for routine public health surveillance rely on centralized collection of potentially identifiable, individual, identifiable personal health information (PHI) records. Although individual, identifiable patient records are essential for conditions for which there is mandated reporting, such as tuberculosis or sexually transmitted diseases, they are not routinely required for effective syndromic surveillance. Public concern about the routine collection of large quantities of PHI to support non-traditional public health functions may make alternative surveillance methods that do not rely on centralized identifiable PHI databases increasingly desirable. METHODS: The National Bioterrorism Syndromic Surveillance Demonstration Program (NDP) is an example of one alternative model. All PHI in this system is initially processed within the secured infrastructure of the health care provider that collects and holds the data, using uniform software distributed and supported by the NDP. Only highly aggregated count data is transferred to the datacenter for statistical processing and display. RESULTS: Detailed, patient level information is readily available to the health care provider to elucidate signals observed in the aggregated data, or for ad hoc queries. We briefly describe the benefits and disadvantages associated with this distributed processing model for routine automated syndromic surveillance. CONCLUSION: For well-defined surveillance requirements, the model can be successfully deployed with very low risk of inadvertent disclosure of PHI – a feature that may make participation in surveillance systems more feasible for organizations and more appealing to the individuals whose PHI they hold. It is possible to design and implement distributed systems to support non-routine public health needs if required.",2006 Sep 19,"['Lazarus, Ross', 'Yih, Katherine', 'Platt, Richard']",BMC Public Health,,,True
ffe04775867d268ef18a29f13138e407b6aa8ea5,PMC,Clinical and epidemiological predictors of transmission in Severe Acute Respiratory Syndrome (SARS),http://dx.doi.org/10.1186/1471-2334-6-151,PMC1624840,17049088,CC BY,"BACKGROUND: Only a minority of probable SARS cases caused transmission. We assess if any epidemiological or clinical factors in SARS index patients were associated with increased probability of transmission. METHODS: We used epidemiological and clinical data on probable SARS patients admitted to Tan Tock Seng Hospital. Using a case-control approach, index patients who had probable SARS who subsequently transmitted the disease to at least one other patient were analysed as ""cases"" against patients with no transmission as ""controls"", using multivariate logistic regression analysis. RESULTS: 98 index patients were available for analysis (22 with transmission, 76 with no transmission). Covariates positively associated with transmission in univariate analysis at p < 0.05 included delay to isolation (Day 7 of illness or later), admission to a non-isolation facility, pre-existing chronic respiratory disease and immunosuppressive disease, need for oxygen, shortness of breath, vomiting, and higher lactate dehydrogenase levels and higher neutrophil counts. In the multivariate analysis, only three factors were significant: delay to isolation, admission to a non-isolation facility and higher lactate dehydrogenase levels of >650 IU/L (OR 6.4, 23.8 and 4.7 respectively). CONCLUSION: Clinical and epidemiological factors can help us to explain why transmission was observed in some instances but not in others.",2006 Oct 18,"['Chen, Mark IC', 'Chow, Angela LP', 'Earnest, Arul', 'Leong, Hoe Nam', 'Leo, Yee Sin']",BMC Infect Dis,,,True
0491da5ae5c2fa38824350bde5462ed82ebc24e7,PMC,Immunogenicity of a polyvalent HIV-1 candidate vaccine based on fourteen wild type gp120 proteins in golden hamsters,http://dx.doi.org/10.1186/1471-2172-7-25,PMC1636068,17076905,CC BY,"BACKGROUND: One of the major obstacles in the design of an effective vaccine against HIV-1 is the hypervariability of the HIV-1 envelope glycoprotein. Most HIV-1 vaccine candidates have utilized envelope glycoprotein from a single virus isolate, but to date, none of them elicited broadly reactive humoral immunity. Herein, we hypothesised that a cocktail of HIV-1 gp120 proteins containing multiple epitopes may increase the breadth of immune responses against HIV-1. We compared and evaluated the immunogenicity of HIV-1 vaccines containing either gp120 protein alone or in combinations of four or fourteen gp120s from different primary HIV-1 isolates in immunized hamsters. RESULTS: We amplified and characterized 14 different gp120s from primary subtype B isolates with both syncytium and non-syncytium inducing properties, and expressed the proteins in Chinese Hamster Ovary (CHO) cell lines. Purified proteins were used either alone or in combinations of four or fourteen different gp120s to vaccinate golden hamsters. The polyvalent vaccine showed higher antibody titers to HIV-1 subtype B isolates MN and SF162 compared to the groups that received one or four gp120 proteins. However, the polyvalent vaccine was not able to show higher neutralizing antibody responses against HIV-1 primary isolates. Interestingly, the polyvalent vaccine group had the highest proliferative immune responses and showed a substantial proportion of cross-subtype CD4 reactivity to HIV-1 subtypes B, C, and A/E CONCLUSION: Although the polyvalent approach achieved only a modest increase in the breadth of humoral and cellular immunity, the qualitative change in the vaccine (14 vs. 1 gp120) resulted in a quantitative improvement in vaccine-induced immunity.",2006 Oct 31,"['Azizi, Ali', 'Anderson, David E', 'Ghorbani, Masoud', 'Gee, Katrina', 'Diaz-Mitoma, Francisco']",BMC Immunol,,,True
c7d86587837b09a6b722f78beac7bfedaa0333d3,PMC,Structure-based discovery of inhibitors of the YycG histidine kinase: New chemical leads to combat Staphylococcus epidermidis infections,http://dx.doi.org/10.1186/1471-2180-6-96,PMC1660542,17094812,CC BY,"BACKGROUND: Coagulase-negative Staphylococcus epidermidis has become a major frequent cause of infections in relation to the use of implanted medical devices. The pathogenicity of S. epidermidis has been attributed to its capacity to form biofilms on surfaces of medical devices, which greatly increases its resistance to many conventional antibiotics and often results in chronic infection. It has an urgent need to design novel antibiotics against staphylococci infections, especially those can kill cells embedded in biofilm. RESULTS: In this report, a series of novel inhibitors of the histidine kinase (HK) YycG protein of S. epidermidis were discovered first using structure-based virtual screening (SBVS) from a small molecular lead-compound library, followed by experimental validation. Of the 76 candidates derived by SBVS targeting of the homolog model of the YycG HATPase_c domain of S. epidermidis, seven compounds displayed significant activity in inhibiting S. epidermidis growth. Furthermore, five of them displayed bactericidal effects on both planktonic and biofilm cells of S. epidermidis. Except for one, the compounds were found to bind to the YycG protein and to inhibit its auto-phosphorylation in vitro, indicating that they are potential inhibitors of the YycG/YycF two-component system (TCS), which is essential in S. epidermidis. Importantly, all these compounds did not affect the stability of mammalian cells nor hemolytic activities at the concentrations used in our study. CONCLUSION: These novel inhibitors of YycG histidine kinase thus are of potential value as leads for developing new antibiotics against infecting staphylococci. The structure-based virtual screening (SBVS) technology can be widely used in screening potential inhibitors of other bacterial TCSs, since it is more rapid and efficacious than traditional screening technology.",2006 Nov 10,"['Qin, Zhiqiang', 'Zhang, Jian', 'Xu, Bin', 'Chen, Lili', 'Wu, Yang', 'Yang, Xiaomei', 'Shen, Xu', 'Molin, Soeren', 'Danchin, Antoine', 'Jiang, Hualiang', 'Qu, Di']",BMC Microbiol,,,True
86fe00ed292aab3fd191a7f8253d33dad3be59b3,PMC,Distinct cellular responses differentiating alcohol- and hepatitis C virus-induced liver cirrhosis,http://dx.doi.org/10.1186/1743-422X-3-98,PMC1676004,17121680,CC BY,"BACKGROUND: Little is known at the molecular level concerning the differences and/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV). RESULTS: Global gene expression patterns varied significantly depending upon etiology of liver disease, with a greater number of differentially regulated genes seen in HCV-infected patients. Many of the gene expression changes specifically observed in HCV-infected cirrhotic livers were expectedly associated with activation of the innate antiviral immune response. We also compared severity (CTP class) of cirrhosis for each etiology and identified gene expression patterns that differentiated ethanol-induced cirrhosis by class. CTP class A ethanol-cirrhotic livers showed unique expression patterns for genes implicated in the inflammatory response, including those related to macrophage activation and migration, as well as lipid metabolism and oxidative stress genes. CONCLUSION: Stages of liver cirrhosis could be differentiated based on gene expression patterns in ethanol-induced, but not HCV-induced, disease. In addition to genes specifically regulating the innate antiviral immune response, mechanisms responsible for differentiating chronic liver damage due to HCV or ethanol may be closely related to regulation of lipid metabolism and to effects of macrophage activation on deposition of extracellular matrix components.",2006 Nov 22,"['Lederer, Sharon L', 'Walters, Kathie-Anne', 'Proll, Sean', 'Paeper, Bryan', 'Robinzon, Shahar', 'Boix, Loreto', 'Fausto, Nelson', 'Bruix, Jordi', 'Katze, Michael G']",Virol J,,,True
c878b060760db3b59ae0129a5de677e56a30866e,PMC,"Improving the use of research evidence in guideline development: 13. Applicability, transferability and adaptation",http://dx.doi.org/10.1186/1478-4505-4-25,PMC1712227,17156457,CC BY,"BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the thirteenth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on applicability, transferability, and adaptation of guidelines. METHODS: We searched five databases for existing systematic reviews and relevant primary methodological research. We reviewed the titles of all citations and retrieved abstracts and full text articles if the citations appeared relevant to the topic. We checked the reference lists of articles relevant to the questions and used snowballing as a technique to obtain additional information. We used the definition ""coming from, concerning or belonging to at least two or all nations"" for the term international. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: We did not identify systematic reviews addressing the key questions. We found individual studies and projects published in the peer reviewed literature and on the Internet. Should WHO develop international recommendations? • Resources for developing high quality recommendations are limited. Internationally developed recommendations can facilitate access to and pooling of resources, reduce unnecessary duplication, and involve international scientists. • Priority should be given to international health problems and problems that are important in low and middle-income countries, where these advantages are likely to be greatest. • Factors that influence the transferability of recommendations across different settings should be considered systematically and flagged, including modifying factors, important variation in needs, values, costs and the availability of resources. What should be done centrally and locally? • The preparation of systematic reviews and evidence profiles should be coordinated centrally, in collaboration with organizations that produce systematic reviews. Centrally developed evidence profiles should be adaptable to specific local circumstances. • Consideration should be given to models that involve central coordination with work being undertaken by centres located throughout the world. • While needs, availability of resources, costs, the presence of modifying factors and values need to be assessed locally, support for undertaking these assessments may be needed to make guidelines applicable. • WHO should provide local support for adapting and implementing recommendations by developing tools, building capacity, learning from international experience, and through international networks that support evidence-informed health policies, such as the Evidence-informed Policy Network (EVIPNet). How should recommendations be adapted? • WHO should provide detailed guidance for adaptation of international recommendations. • Local adaptation processes should be systematic and transparent, they should involve stakeholders, and they should report the key factors that influence decisions, including those flagged in international guidelines, and the reasons for any modifications that are made.",2006 Dec 8,"['Schünemann, Holger J', 'Fretheim, Atle', 'Oxman, Andrew D']",Health Res Policy Syst,,,True
4bf165f82a8648b69169a66114d29c690f0562e0,PMC,Modeling early recovery of physical function following hip and knee arthroplasty,http://dx.doi.org/10.1186/1471-2474-7-100,PMC1712335,17156487,CC BY,"BACKGROUND: Information on early recovery after arthroplasty is needed to help benchmark progress and make appropriate decisions concerning patient rehabilitation needs. The purpose of this study was to model early recovery of physical function in patients undergoing total hip (THA) and knee (TKA) arthroplasty, using physical performance and self-report measures. METHODS: A sample of convenience of 152 subjects completed testing, of which 69 (mean age: 66.77 ± 8.23 years) underwent THA and 83 (mean age: 60.25 ± 11.19 years) TKA. Postoperatively, patients were treated using standardized care pathways and rehabilitation protocols. Using a repeated measures design, patients were assessed at multiple time points over the first four postoperative months. Outcome measures included the Lower Extremity Function Scale (LEFS), the physical function subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC PF), the 6 minute walk test (6 MWT), timed up and go test (TUG) and a timed stair test (ST). Average recovery curves for each of the measures were characterized using hierarchical linear modeling. Predictors of recovery were sequentially modeled after validation of the basic developmental models. RESULTS: Slopes of recovery were greater in the first 6 to 9 weeks with a second-degree polynomial growth term (weeks squared) providing a reasonable fit for the data over the study interval. Different patterns of recovery were observed between the self-report measures of physical function and the performance measures. In contrast to the models for the WOMAC PF and the LEFS, site of arthroplasty was a significant predictor (p = 0.001) in all of the physical performance measure models with the patients post TKA initially demonstrating higher function. Site of arthroplasty (p = 0.025) also predicted the rate of change for patients post THA and between 9 to 11 weeks after surgery, the THA group surpassed the function of the patients post TKA. CONCLUSION: Knowledge about the predicted growth curves will assist clinicians in referencing patient progress, and determining the critical time points for measuring change. The study has contributed further evidence to highlight the benefit of using physical performance measures to learn about the patients' actual level of disability.",2006 Dec 11,"['Kennedy, Deborah M', 'Stratford, Paul W', 'Hanna, Steven E', 'Wessel, Jean', 'Gollish, Jeffrey D']",BMC Musculoskelet Disord,,,True
29b6131c0d572d383cbc6774b12e4471aa612b07,PMC,Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants,http://dx.doi.org/10.1371/journal.pmed.0030525,PMC1716185,17194199,CC BY,"BACKGROUND: In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) was identified as the etiological agent of severe acute respiratory syndrome, a disease characterized by severe pneumonia that sometimes results in death. SARS-CoV is a zoonotic virus that crossed the species barrier, most likely originating from bats or from other species including civets, raccoon dogs, domestic cats, swine, and rodents. A SARS-CoV vaccine should confer long-term protection, especially in vulnerable senescent populations, against both the 2003 epidemic strains and zoonotic strains that may yet emerge from animal reservoirs. We report the comprehensive investigation of SARS vaccine efficacy in young and senescent mice following homologous and heterologous challenge. METHODS AND FINDINGS: Using Venezuelan equine encephalitis virus replicon particles (VRP) expressing the 2003 epidemic Urbani SARS-CoV strain spike (S) glycoprotein (VRP-S) or the nucleocapsid (N) protein from the same strain (VRP-N), we demonstrate that VRP-S, but not VRP-N vaccines provide complete short- and long-term protection against homologous strain challenge in young and senescent mice. To test VRP vaccine efficacy against a heterologous SARS-CoV, we used phylogenetic analyses, synthetic biology, and reverse genetics to construct a chimeric virus (icGDO3-S) encoding a synthetic S glycoprotein gene of the most genetically divergent human strain, GDO3, which clusters among the zoonotic SARS-CoV. icGD03-S replicated efficiently in human airway epithelial cells and in the lungs of young and senescent mice, and was highly resistant to neutralization with antisera directed against the Urbani strain. Although VRP-S vaccines provided complete short-term protection against heterologous icGD03-S challenge in young mice, only limited protection was seen in vaccinated senescent animals. VRP-N vaccines not only failed to protect from homologous or heterologous challenge, but resulted in enhanced immunopathology with eosinophilic infiltrates within the lungs of SARS-CoV–challenged mice. VRP-N–induced pathology presented at day 4, peaked around day 7, and persisted through day 14, and was likely mediated by cellular immune responses. CONCLUSIONS: This study identifies gaps and challenges in vaccine design for controlling future SARS-CoV zoonosis, especially in vulnerable elderly populations. The availability of a SARS-CoV virus bearing heterologous S glycoproteins provides a robust challenge inoculum for evaluating vaccine efficacy against zoonotic strains, the most likely source of future outbreaks.",2006 Dec 26,"['Deming, Damon', 'Sheahan, Timothy', 'Heise, Mark', 'Yount, Boyd', 'Davis, Nancy', 'Sims, Amy', 'Suthar, Mehul', 'Harkema, Jack', 'Whitmore, Alan', 'Pickles, Raymond', 'West, Ande', 'Donaldson, Eric', 'Curtis, Kristopher', 'Johnston, Robert', 'Baric, Ralph']",PLoS Med,,,True
89eb2ddb11e00fa7652c170a84d919d2428d90f8,PMC,Epidemiology and clinical outcome of virus-positive respiratory samples in ventilated patients: a prospective cohort study,http://dx.doi.org/10.1186/cc5059,PMC1751045,17022805,CC BY,"INTRODUCTION: Respiratory viruses are a major cause of respiratory tract infections. The prevalence of a virus-positive respiratory sample and its significance in patients requiring mechanical ventilation remain unknown. METHODS: We conducted a cohort study in all consecutive adults ventilated for more than 48 hours admitted to a 22-bed medical intensive care unit during a 12-month period. Respiratory samples at the time of intubation were assessed by culture, by indirect immunofluorescence assay or by molecular methods in systematic tracheobronchial aspirates. Patients with a virus-negative respiratory sample at the time of intubation were considered unexposed and served as the control group. RESULTS: Forty-five viruses were isolated in 41/187 (22%) patients. Rhinovirus was the most commonly isolated virus (42%), followed byherpes simplex virus type 1 (22%) and virus influenza A (16%). In multivariate analysis controlling for the Acute Pathophysiology and Chronic Health Evaluation II score, patients with respiratory disorder at admission (adjusted odds ratio, 2.1; 95% confidence interval, 0.8–5.1; P = 0.12), with chronic obstructive pulmonary disease/asthma patients (adjusted odds ratio, 3.0; 95% confidence interval, 1.3–6.7; P = 0.01) and with admission between 21 November and 21 March (adjusted odds ratio, 2.8; 95% confidence interval, 1.3–5.9; P = 0.008) were independently associated with a virus-positive sample. Among the 122 patients admitted with respiratory disorder, a tracheobronchial aspirate positive for respiratory viruses at the time of intubation (adjusted hazard ratio, 0.273; 95% confidence interval, 0.096–0.777; P < 0.006) was independently associated with better survival, controlling for the Simplified Acute Physiology Score II and admission for cardiogenic shock or cardiac arrest. Among the remaining 65 patients, a virus-positive sample on intubation did not predict survival. CONCLUSION: We confirmed the pathogenic role of respiratory viruses in the intensive care unit, particularly rhinovirus. We suggest, however, that the prognostic value of virus-associated respiratory disorder is better than that of other causes of respiratory disorder.",2006 Oct 5,"['Daubin, Cédric', 'Parienti, Jean-Jacques', 'Vincent, Sophie', 'Vabret, Astrid', 'du Cheyron, Damien', 'Ramakers, Michel', 'Freymuth, François', 'Charbonneau, Pierre']",Crit Care,,,True
19717b7bfa9911835e3c0085633f6dec5453da9a,PMC,Societal Learning in Epidemics: Intervention Effectiveness during the 2003 SARS Outbreak in Singapore,http://dx.doi.org/10.1371/journal.pone.0000020,PMC1762333,17183647,CC BY,"BACKGROUND: Rapid response to outbreaks of emerging infectious diseases is impeded by uncertain diagnoses and delayed communication. Understanding the effect of inefficient response is a potentially important contribution of epidemic theory. To develop this understanding we studied societal learning during emerging outbreaks wherein patient removal accelerates as information is gathered and disseminated. METHODS AND FINDINGS: We developed an extension of a standard outbreak model, the simple stochastic epidemic, which accounts for societal learning. We obtained expressions for the expected outbreak size and the distribution of epidemic duration. We found that rapid learning noticeably affects the final outbreak size even when learning exhibits diminishing returns (relaxation). As an example, we estimated the learning rate for the 2003 outbreak of severe acute respiratory syndrome (SARS) in Singapore. Evidence for relaxation during the first eight weeks of the outbreak was inconclusive. We estimated that if societal learning had occurred at half the actual rate, the expected final size of the outbreak would have reached nearly 800 cases, more than three times the observed number of infections. By contrast, the expected outbreak size for societal learning twice as effective was 116 cases. CONCLUSION: These results show that the rate of societal learning can greatly affect the final size of disease outbreaks, justifying investment in early warning systems and attentiveness to disease outbreak by both government authorities and the public. We submit that the burden of emerging infections, including the risk of a global pandemic, could be efficiently reduced by improving procedures for rapid detection of outbreaks, alerting public health officials, and aggressively educating the public at the start of an outbreak.",2006 Dec 20,"['Drake, John M.', 'Chew, Suok Kai', 'Ma, Stefan']",PLoS One,,,True
c64f525d77bf8b2ae4439a875f1bd8eb197a0519,PMC,Association and Host Selectivity in Multi-Host Pathogens,http://dx.doi.org/10.1371/journal.pone.0000041,PMC1762347,17183670,CC BY,"The distribution of multi-host pathogens over their host range conditions their population dynamics and structure. Also, host co-infection by different pathogens may have important consequences for the evolution of hosts and pathogens, and host-pathogen co-evolution. Hence it is of interest to know if the distribution of pathogens over their host range is random, or if there are associations between hosts and pathogens, or between pathogens sharing a host. To analyse these issues we propose indices for the observed patterns of host infection by pathogens, and for the observed patterns of co-infection, and tests to analyse if these patterns conform to randomness or reflect associations. Applying these tests to the prevalence of five plant viruses on 21 wild plant species evidenced host-virus associations: most hosts and viruses were selective for viruses and hosts, respectively. Interestingly, the more host-selective viruses were the more prevalent ones, suggesting that host specialisation is a successful strategy for multi-host pathogens. Analyses also showed that viruses tended to associate positively in co-infected hosts. The developed indices and tests provide the tools to analyse how strong and common are these associations among different groups of pathogens, which will help to understand and model the population biology of multi-host pathogens.",2006 Dec 20,"['Malpica, José M.', 'Sacristán, Soledad', 'Fraile, Aurora', 'García-Arenal, Fernando']",PLoS One,,,True
389612b52a4489f9be2109a5eb0060499a0f7c15,PMC,Long-Term Persistence of Robust Antibody and Cytotoxic T Cell Responses in Recovered Patients Infected with SARS Coronavirus,http://dx.doi.org/10.1371/journal.pone.0000024,PMC1762349,17183651,CC BY,"Most of the individuals infected with SARS coronavirus (SARS-CoV) spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.",2006 Dec 20,"['Li, Taisheng', 'Xie, Jing', 'He, Yuxian', 'Fan, Hongwei', 'Baril, Laurence', 'Qiu, Zhifeng', 'Han, Yang', 'Xu, Wenbing', 'Zhang, Weihong', 'You, Hui', 'Zuo, Yanling', 'Fang, Qing', 'Yu, Jian', 'Chen, Zhiwei', 'Zhang, Linqi']",PLoS One,,,True
6af02873a430f5f75dc56a917f26feaea89b8e79,PMC,The Effectiveness of Contact Tracing in Emerging Epidemics,http://dx.doi.org/10.1371/journal.pone.0000012,PMC1762362,17183638,CC BY,"BACKGROUND: Contact tracing plays an important role in the control of emerging infectious diseases, but little is known yet about its effectiveness. Here we deduce from a generic mathematical model how effectiveness of tracing relates to various aspects of time, such as the course of individual infectivity, the (variability in) time between infection and symptom-based detection, and delays in the tracing process. In addition, the possibility of iteratively tracing of yet asymptomatic infecteds is considered. With these insights we explain why contact tracing was and will be effective for control of smallpox and SARS, only partially effective for foot-and-mouth disease, and likely not effective for influenza. METHODS AND FINDINGS: We investigate contact tracing in a model of an emerging epidemic that is flexible enough to use for most infections. We consider isolation of symptomatic infecteds as the basic scenario, and express effectiveness as the proportion of contacts that need to be traced for a reproduction ratio smaller than 1. We obtain general results for special cases, which are interpreted with respect to the likely success of tracing for influenza, smallpox, SARS, and foot-and-mouth disease epidemics. CONCLUSIONS: We conclude that (1) there is no general predictive formula for the proportion to be traced as there is for the proportion to be vaccinated; (2) variability in time to detection is favourable for effective tracing; (3) tracing effectiveness need not be sensitive to the duration of the latent period and tracing delays; (4) iterative tracing primarily improves effectiveness when single-step tracing is on the brink of being effective.",2006 Dec 20,"['Klinkenberg, Don', 'Fraser, Christophe', 'Heesterbeek, Hans']",PLoS One,,,True
7155c0fda843cfccdbd4bf302b1d7f2c343f528f,PMC,The Effectiveness of Contact Tracing in Emerging Epidemics,http://dx.doi.org/10.1371/journal.pone.0000012,PMC1762362,17183638,CC BY,"BACKGROUND: Contact tracing plays an important role in the control of emerging infectious diseases, but little is known yet about its effectiveness. Here we deduce from a generic mathematical model how effectiveness of tracing relates to various aspects of time, such as the course of individual infectivity, the (variability in) time between infection and symptom-based detection, and delays in the tracing process. In addition, the possibility of iteratively tracing of yet asymptomatic infecteds is considered. With these insights we explain why contact tracing was and will be effective for control of smallpox and SARS, only partially effective for foot-and-mouth disease, and likely not effective for influenza. METHODS AND FINDINGS: We investigate contact tracing in a model of an emerging epidemic that is flexible enough to use for most infections. We consider isolation of symptomatic infecteds as the basic scenario, and express effectiveness as the proportion of contacts that need to be traced for a reproduction ratio smaller than 1. We obtain general results for special cases, which are interpreted with respect to the likely success of tracing for influenza, smallpox, SARS, and foot-and-mouth disease epidemics. CONCLUSIONS: We conclude that (1) there is no general predictive formula for the proportion to be traced as there is for the proportion to be vaccinated; (2) variability in time to detection is favourable for effective tracing; (3) tracing effectiveness need not be sensitive to the duration of the latent period and tracing delays; (4) iterative tracing primarily improves effectiveness when single-step tracing is on the brink of being effective.",2006 Dec 20,"['Klinkenberg, Don', 'Fraser, Christophe', 'Heesterbeek, Hans']",PLoS One,,,False
57d2a2f022fc3ec32d1b92bb0a234c9f4ac8e1d6,PMC,DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques,http://dx.doi.org/10.1371/journal.pone.0000135,PMC1762437,17205139,CC BY,"Previous studies of HIV-1 p55Gag immunization of mice have demonstrated the usefulness of targeting antigens to the cellular compartment containing the major histocompatibility complex type II (MHC II) complex molecules by use of a DNA antigen formulation encoding Gag as a chimera with the mouse lysosome-associated membrane protein (mLAMP/gag). In the present study, we have analyzed the magnitude and breadth of Gag-specific T-lymphocyte and antibody responses elicited in Rhesus macaques after immunization with DNA encoding a human LAMP/gag (hLAMP/gag) chimera. ELISPOT analyses indicated that the average Gag-specific IFN-γ response elicited by the hLAMP/gag chimera was detectable after only two or three naked DNA immunizations in all five immunized macaques and reached an average of 1000 spot-forming cells (SFC)/10(6) PBMCs. High IFN-γ ELISPOT responses were detected in CD8(+)-depleted cells, indicating that CD4(+) T-cells play a major role in these responses. The T-cell responses of four of the macaques were also tested by use of ELISPOT to 12 overlapping 15-amino acids (aa) peptide pools containing ten peptides each, encompassing the complete Gag protein sequence. The two Mamu 08 immunized macaques responded to eight and twelve of the pools, the Mamu B01 to six, and the other macaque to five pools indicating that the hLAMP/gag DNA antigen formulation elicits a broad T-cell response against Gag. Additionally, there was a strong HIV-1-specific IgG response. The IgG antibody titers increased after each DNA injection, indicating a strong amnestic B-cell response, and were highly elevated in all the macaques after three immunizations. Moreover, the serum of each macaque recognized 13 of the 49 peptides of a 20-aa peptide library covering the complete Gag amino acid sequence. In addition, HIV-1-specific IgA antibodies were present in the plasma and external secretions, including nasal washes. These data support the findings of increased immunogenicity of genetic vaccines encoded as LAMP chimeras, including the response to DNA vaccines by non-human primates.",2006 Dec 27,"['Chikhlikar, Priya', 'de Arruda, Luciana Barros', 'Maciel, Milton', 'Silvera, Peter', 'Lewis, Mark G.', 'August, J. Thomas', 'Marques, Ernesto T.A.']",PLoS One,,,True
bcb21b0dcaf5456200446cd3e1c6ad1990253dbf,PMC,The effect of travel restrictions on the spread of a moderately contagious disease,http://dx.doi.org/10.1186/1741-7015-4-32,PMC1764026,17166291,CC BY,"BACKGROUND: Much research in epidemiology has been focused on evaluating conventional methods of control strategies in the event of an epidemic or pandemic. Travel restrictions are often suggested as an efficient way to reduce the spread of a contagious disease that threatens public health, but few papers have studied in depth the effects of travel restrictions. In this study, we investigated what effect different levels of travel restrictions might have on the speed and geographical spread of an outbreak of a disease similar to severe acute respiratory syndrome (SARS). METHODS: We used a stochastic simulation model incorporating survey data of travel patterns between municipalities in Sweden collected over 3 years. We tested scenarios of travel restrictions in which travel over distances >50 km and 20 km would be banned, taking into account different levels of compliance. RESULTS: We found that a ban on journeys >50 km would drastically reduce the speed and geographical spread of outbreaks, even when compliance is < 100%. The result was found to be robust for different rates of intermunicipality transmission intensities. CONCLUSION: This study supports travel restrictions as an effective way to mitigate the effect of a future disease outbreak.",2006 Dec 14,"['Camitz, Martin', 'Liljeros, Fredrik']",BMC Med,,,True
9b7a0ad7b6c7f59e7a6cf1dc9d07912a273d19b5,PMC,The Waiting Time for Inter-Country Spread of Pandemic Influenza,http://dx.doi.org/10.1371/journal.pone.0000143,PMC1764036,17206278,CC BY,"BACKGROUND: The time delay between the start of an influenza pandemic and its subsequent initiation in other countries is highly relevant to preparedness planning. We quantify the distribution of this random time in terms of the separate components of this delay, and assess how the delay may be extended by non-pharmaceutical interventions. METHODS AND FINDINGS: The model constructed for this time delay accounts for: (i) epidemic growth in the source region, (ii) the delay until an infected individual from the source region seeks to travel to an at-risk country, (iii) the chance that infected travelers are detected by screening at exit and entry borders, (iv) the possibility of in-flight transmission, (v) the chance that an infected arrival might not initiate an epidemic, and (vi) the delay until infection in the at-risk country gathers momentum. Efforts that reduce the disease reproduction number in the source region below two and severe travel restrictions are most effective for delaying a local epidemic, and under favourable circumstances, could add several months to the delay. On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. Elevated in-flight transmission reduces the delay only minimally. CONCLUSIONS: The delay until an epidemic of pandemic strain influenza is imported into an at-risk country is largely determined by the course of the epidemic in the source region and the number of travelers attempting to enter the at-risk country, and is little affected by non-pharmaceutical interventions targeting these travelers. Short of preventing international travel altogether, eradicating a nascent pandemic in the source region appears to be the only reliable method of preventing country-to-country spread of a pandemic strain of influenza.",2007 Jan 3,"['Caley, Peter', 'Becker, Niels G.', 'Philp, David J.']",PLoS One,,,True
5ec4b4abb2bca7c9a189f466680e47fd5f56486e,PMC,The Waiting Time for Inter-Country Spread of Pandemic Influenza,http://dx.doi.org/10.1371/journal.pone.0000143,PMC1764036,17206278,CC BY,"BACKGROUND: The time delay between the start of an influenza pandemic and its subsequent initiation in other countries is highly relevant to preparedness planning. We quantify the distribution of this random time in terms of the separate components of this delay, and assess how the delay may be extended by non-pharmaceutical interventions. METHODS AND FINDINGS: The model constructed for this time delay accounts for: (i) epidemic growth in the source region, (ii) the delay until an infected individual from the source region seeks to travel to an at-risk country, (iii) the chance that infected travelers are detected by screening at exit and entry borders, (iv) the possibility of in-flight transmission, (v) the chance that an infected arrival might not initiate an epidemic, and (vi) the delay until infection in the at-risk country gathers momentum. Efforts that reduce the disease reproduction number in the source region below two and severe travel restrictions are most effective for delaying a local epidemic, and under favourable circumstances, could add several months to the delay. On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. Elevated in-flight transmission reduces the delay only minimally. CONCLUSIONS: The delay until an epidemic of pandemic strain influenza is imported into an at-risk country is largely determined by the course of the epidemic in the source region and the number of travelers attempting to enter the at-risk country, and is little affected by non-pharmaceutical interventions targeting these travelers. Short of preventing international travel altogether, eradicating a nascent pandemic in the source region appears to be the only reliable method of preventing country-to-country spread of a pandemic strain of influenza.",2007 Jan 3,"['Caley, Peter', 'Becker, Niels G.', 'Philp, David J.']",PLoS One,,,False
bd9162d8379baef31b50aa17a7f553740aa28ba2,PMC,"Curation of viral genomes: challenges, applications and the way forward",http://dx.doi.org/10.1186/1471-2105-7-S5-S12,PMC1764468,17254296,CC BY,"BACKGROUND: Whole genome sequence data is a step towards generating the 'parts list' of life to understand the underlying principles of Biocomplexity. Genome sequencing initiatives of human and model organisms are targeted efforts towards understanding principles of evolution with an application envisaged to improve human health. These efforts culminated in the development of dedicated resources. Whereas a large number of viral genomes have been sequenced by groups or individuals with an interest to study antigenic variation amongst strains and species. These independent efforts enabled viruses to attain the status of 'best-represented taxa' with the highest number of genomes. However, due to lack of concerted efforts, viral genomic sequences merely remained as entries in the public repositories until recently. RESULTS: VirGen is a curated resource of viral genomes and their analyses. Since its first release, it has grown both in terms of coverage of viral families and development of new modules for annotation and analysis. The current release (2.0) includes data for twenty-five families with broad host range as against eight in the first release. The taxonomic description of viruses in VirGen is in accordance with the ICTV nomenclature. A well-characterised strain is identified as a 'representative entry' for every viral species. This non-redundant dataset is used for subsequent annotation and analyses using sequenced-based Bioinformatics approaches. VirGen archives precomputed data on genome and proteome comparisons. A new data module that provides structures of viral proteins available in PDB has been incorporated recently. One of the unique features of VirGen is predicted conformational and sequential epitopes of known antigenic proteins using in-house developed algorithms, a step towards reverse vaccinology. CONCLUSION: Structured organization of genomic data facilitates use of data mining tools, which provides opportunities for knowledge discovery. One of the approaches to achieve this goal is to carry out functional annotations using comparative genomics. VirGen, a comprehensive viral genome resource that serves as an annotation and analysis pipeline has been developed for the curation of public domain viral genome data . Various steps in the curation and annotation of the genomic data and applications of the value-added derived data are substantiated with case studies.",2006 Dec 18,"['Kulkarni-Kale, Urmila', 'Bhosle, Shriram G', 'Manjari, G Sunitha', 'Joshi, Manali', 'Bansode, Sandeep', 'Kolaskar, Ashok S']",BMC Bioinformatics,,,True
b8e80e078c91d674918e69168da4085a9e176053,PMC,Influenza pandemic and professional duty: family or patients first? A survey of hospital employees,http://dx.doi.org/10.1186/1471-2458-6-311,PMC1764890,17192198,CC BY,"BACKGROUND: Conflicts between professional duties and fear of influenza transmission to family members may arise among health care professionals (HCP). METHODS: We surveyed employees at our university hospital regarding ethical issues arising during the management of an influenza pandemic. RESULTS: Of 644 respondents, 182 (28%) agreed that it would be professionally acceptable for HCP to abandon their workplace during a pandemic in order to protect themselves and their families, 337 (52%) disagreed with this statement and 125 (19%) had no opinion, with a higher rate of disagreement among physicians (65%) and nurses (54%) compared with administrators (32%). Of all respondents, 375 (58%) did not believe that the decision to report to work during a pandemic should be left to the individual HCP and 496 (77%) disagreed with the statement that HCP should be permanently dismissed for not reporting to work during a pandemic. Only 136 (21%) respondents agreed that HCW without children should primarily care for the influenza patients. CONCLUSION: Our results suggest that a modest majority of HCP, but only a minority of hospital administrators, recognises the obligation to treat patients despite the potential risks. Professional ethical guidelines allowing for balancing the needs of society with personal risks are needed to help HCP fulfil their duties in the case of a pandemic influenza.",2006 Dec 28,"['Ehrenstein, Boris P', 'Hanses, Frank', 'Salzberger, Bernd']",BMC Public Health,,,True
fa84d62d8e80e07fdcd1f5543bec8c3f2cb46b74,PMC,Mycoplasma alkalescens demonstrated in bronchoalveolar lavage of cattle in Denmark,http://dx.doi.org/10.1186/1751-0147-49-2,PMC1766361,17204146,CC BY,"Mycoplasma alkalescens is an arginine-metabolizing mycoplasma, which has been found in association with mastitis and arthritis in cattle. Routine bacteriological examination of 17 bronchoalveolar lavage samples from calves with pneumonia in a single herd in Denmark, identified M. alkalescens in eight samples. The organism was found as a sole bacterilogical findings in five of the samples as well as in combination with Mannheimia haemolytica, Haemophilus somni and Salmonella Dublin. This is the first report of isolation of M. alkalescens in Denmark.",2007 Jan 4,"['Kokotovic, Branko', 'Friis, Niels F', 'Ahrens, Peter']",Acta Vet Scand,,,True
4b9911544622c1028499e1db9cf9fb783c2ed863,PMC,"Proteomic Profiling of the Amniotic Fluid to Detect Inflammation, Infection, and Neonatal Sepsis",http://dx.doi.org/10.1371/journal.pmed.0040018,PMC1769412,17227133,CC BY,"BACKGROUND: Proteomic analysis of amniotic fluid shows the presence of biomarkers characteristic of intrauterine inflammation. We sought to validate prospectively the clinical utility of one such proteomic profile, the Mass Restricted (MR) score. METHODS AND FINDINGS: We enrolled 169 consecutive women with singleton pregnancies admitted with preterm labor or preterm premature rupture of membranes. All women had a clinically indicated amniocentesis to rule out intra-amniotic infection. A proteomic fingerprint (MR score) was generated from fresh samples of amniotic fluid using surface-enhanced laser desorption ionization (SELDI) mass spectrometry. Presence or absence of the biomarkers of the MR score was interpreted in relationship to the amniocentesis-to-delivery interval, placental inflammation, and early-onset neonatal sepsis for all neonates admitted to the Newborn Special Care Unit (n = 104). Women with “severe” amniotic fluid inflammation (MR score of 3 or 4) had shorter amniocentesis-to-delivery intervals than women with “no” (MR score of 0) inflammation or even “minimal” (MR score of 1 or 2) inflammation (median [range] MR 3–4: 0.4 d [0.0–49.6 d] versus MR 1–2: 3.8 d [0.0–151.2 d] versus MR 0: 17.0 d [0.1–94.3 d], p < 0.001). Nonetheless, a “minimal” degree of inflammation was also associated with preterm birth regardless of membrane status. There was a significant association between the MR score and severity of histological chorioamnionitis (r = 0.599, p < 0.001). Furthermore, neonatal hematological indices and early-onset sepsis significantly correlated with the MR score even after adjusting for gestational age at birth (OR for MR 3–4: 3.3 [95% CI, 1.1 to 9.2], p = 0.03). When compared with other laboratory tests routinely used to diagnose amniotic fluid inflammation and infection, the MR score had the highest accuracy to detect inflammation (white blood cell count > 100 cells/mm(3)), whereas the combination of Gram stain and MR score was best for rapid prediction of intra-amniotic infection (positive amniotic fluid culture). CONCLUSIONS: High MR scores are associated with preterm delivery, histological chorioamnionitis, and early-onset neonatal sepsis. In this study, proteomic analysis of amniotic fluid was shown to be the most accurate test for diagnosis of intra-amniotic inflammation, whereas addition of the MR score to the Gram stain provides the best combination of tests to rapidly predict infection.",2007 Jan 16,"['Buhimschi, Catalin S', 'Bhandari, Vineet', 'Hamar, Benjamin D', 'Bahtiyar, Mert-Ozan', 'Zhao, Guomao', 'Sfakianaki, Anna K', 'Pettker, Christian M', 'Magloire, Lissa', 'Funai, Edmund', 'Norwitz, Errol R', 'Paidas, Michael', 'Copel, Joshua A', 'Weiner, Carl P', 'Lockwood, Charles J', 'Buhimschi, Irina A']",PLoS Med,,,True
979eb6ed6241fecc3000a963222725a6439b2e19,PMC,Human coronavirus 229E encodes a single ORF4 protein between the spike and the envelope genes,http://dx.doi.org/10.1186/1743-422X-3-106,PMC1774570,17194306,CC BY,"BACKGROUND: The genome of coronaviruses contains structural and non-structural genes, including several so-called accessory genes. All group 1b coronaviruses encode a single accessory protein between the spike and envelope genes, except for human coronavirus (HCoV) 229E. The prototype virus has a split gene, encoding the putative ORF4a and ORF4b proteins. To determine whether primary HCoV-229E isolates exhibit this unusual genome organization, we analyzed the ORF4a/b region of five current clinical isolates from The Netherlands and three early isolates collected at the Common Cold Unit (CCU) in Salisbury, UK. RESULTS: All Dutch isolates were identical in the ORF4a/b region at amino acid level. All CCU isolates are only 98% identical to the Dutch isolates at the nucleotide level, but more closely related to the prototype HCoV-229E (>98%). Remarkably, our analyses revealed that the laboratory adapted, prototype HCoV-229E has a 2-nucleotide deletion in the ORF4a/b region, whereas all clinical isolates carry a single ORF, 660 nt in size, encoding a single protein of 219 amino acids, which is a homologue of the ORF3 proteins encoded by HCoV-NL63 and PEDV. CONCLUSION: Thus, the genome organization of the group 1b coronaviruses HCoV-NL63, PEDV and HCoV-229E is identical. It is possible that extensive culturing of the HCoV-229E laboratory strain resulted in truncation of ORF4. This may indicate that the protein is not essential in cell culture, but the highly conserved amino acid sequence of the ORF4 protein among clinical isolates suggests that the protein plays an important role in vivo.",2006 Dec 28,"['Dijkman, Ronald', 'Jebbink, Maarten F', 'Wilbrink, Berry', 'Pyrc, Krzysztof', 'Zaaijer, Hans L', 'Minor, Philip D', 'Franklin, Sally', 'Berkhout, Ben', 'Thiel, Volker', 'van der Hoek, Lia']",Virol J,,,True
b6353f8b0fcd86c2fd1e6f27c9b18a3ccc07980b,PMC,Neutralizing Antibody Fails to Impact the Course of Ebola Virus Infection in Monkeys,http://dx.doi.org/10.1371/journal.ppat.0030009,PMC1779296,17238286,CC0,"Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques. This antibody was previously shown to fully protect guinea pigs from infection. Four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody KZ52 intravenously 1 d before challenge with 1,000 plaque-forming units of Ebola virus, followed by a second dose of 50 mg/kg antibody 4 d after challenge. A control animal was exposed to virus in the absence of antibody treatment. Passive transfer of the neutralizing human monoclonal antibody not only failed to protect macaques against challenge with Ebola virus but also had a minimal effect on the explosive viral replication following infection. We show that the inability of antibody to impact infection was not due to neutralization escape. It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody.",2007 Jan 19,"['Oswald, Wendelien B', 'Geisbert, Thomas W', 'Davis, Kelly J', 'Geisbert, Joan B', 'Sullivan, Nancy J', 'Jahrling, Peter B', 'Parren, Paul W. H. I', 'Burton, Dennis R']",PLoS Pathog,,,True
4b2b67b0f48b99e75c190ad11bc215bb5f27503f,PMC,XDR-TB in South Africa: No Time for Denial or Complacency,http://dx.doi.org/10.1371/journal.pmed.0040050,PMC1779818,17253901,CC BY,"Singh and colleagues discuss the threat to regional and global public health posed by XDR-TB in KwaZulu-Natal, and propose new measures to control the outbreak.",2007 Jan 23,"['Singh, Jerome Amir', 'Upshur, Ross', 'Padayatchi, Nesri']",PLoS Med,,,True
fbad56e66ee9453d193dfbbd775248044e0af261,PMC,GraphDNA: a Java program for graphical display of DNA composition analyses,http://dx.doi.org/10.1186/1471-2105-8-21,PMC1783863,17244370,CC BY,"BACKGROUND: Under conditions of no strand bias the number of Gs is equal to that of Cs for each DNA strand; similarly, the total number of Ts is equal to that of As. However, within each strand there are considerable local deviations from the A = T and G = C equality. These asymmetries in nucleotide composition have been extensively analyzed in prokaryotic and eukaryotic genomes and related to chromosome organization, transcription orientation and other processes in certain organisms. To carry out analysis of intra-strand nucleotide distribution several graphical methods have been developed. RESULTS: GraphDNA is a new Java application that provides a simple, user-friendly interface for the visualization of DNA nucleotide composition. The program accepts GenBank, EMBL and FASTA files as an input, and it displays multiple DNA nucleotide composition graphs (skews and walks) in a single window to allow direct comparisons between the sequences. We illustrate the use of DNA skews for characterization of poxvirus and coronavirus genomes. CONCLUSION: GraphDNA is a platform-independent, Open Source, tool for the analysis of nucleotide trends in DNA sequences. Multiple sequence formats can be read and multiple sequences may be plotted in a single results window.",2007 Jan 23,"['Thomas, Jamie M', 'Horspool, Daniel', 'Brown, Gordon', 'Tcherepanov, Vasily', 'Upton, Chris']",BMC Bioinformatics,,,True
247d3262ad1b15f331a89f70eec56b34dbe6b8b5,PMC,"Maximum Likelihood Estimation of the Negative Binomial Dispersion Parameter for Highly Overdispersed Data, with Applications to Infectious Diseases",http://dx.doi.org/10.1371/journal.pone.0000180,PMC1791715,17299582,CC BY,"BACKGROUND: The negative binomial distribution is used commonly throughout biology as a model for overdispersed count data, with attention focused on the negative binomial dispersion parameter, k. A substantial literature exists on the estimation of k, but most attention has focused on datasets that are not highly overdispersed (i.e., those with k≥1), and the accuracy of confidence intervals estimated for k is typically not explored. METHODOLOGY: This article presents a simulation study exploring the bias, precision, and confidence interval coverage of maximum-likelihood estimates of k from highly overdispersed distributions. In addition to exploring small-sample bias on negative binomial estimates, the study addresses estimation from datasets influenced by two types of event under-counting, and from disease transmission data subject to selection bias for successful outbreaks. CONCLUSIONS: Results show that maximum likelihood estimates of k can be biased upward by small sample size or under-reporting of zero-class events, but are not biased downward by any of the factors considered. Confidence intervals estimated from the asymptotic sampling variance tend to exhibit coverage below the nominal level, with overestimates of k comprising the great majority of coverage errors. Estimation from outbreak datasets does not increase the bias of k estimates, but can add significant upward bias to estimates of the mean. Because k varies inversely with the degree of overdispersion, these findings show that overestimation of the degree of overdispersion is very rare for these datasets.",2007 Feb 14,"Lloyd-Smith, James O.",PLoS One,,,True
c34dcfec2a5e68f31f6a0401d2cd636021d984bc,PMC,ProCAT: a data analysis approach for protein microarrays,http://dx.doi.org/10.1186/gb-2006-7-11-r110,PMC1794587,17109749,CC BY,"Protein microarrays provide a versatile method for the analysis of many protein biochemical activities. Existing DNA microarray analytical methods do not translate to protein microarrays due to differences between the technologies. Here we report a new approach, ProCAT, which corrects for background bias and spatial artifacts, identifies significant signals, filters nonspecific spots, and normalizes the resulting signal to protein abundance. ProCAT provides a powerful and flexible new approach for analyzing many types of protein microarrays.",2006 Nov 16,"['Zhu, Xiaowei', 'Gerstein, Mark', 'Snyder, Michael']",Genome Biol,,,True
3e8d47918fb2187af3e556eaf1d5e343f42b0c06,PMC,Quantification of human bocavirus in lower respiratory tract infections in China,http://dx.doi.org/10.1186/1750-9378-2-3,PMC1796861,17266760,CC BY,"A quantitative PCR method was established to quantify human bocavirus (HBoV) genomic copies in clinical specimens from children with lower respiratory tract infections (LRTI) in China. A total of 257 respiratory tract specimens were tested, and 7 (2.7%) of these (all sputum samples) were positive, with genomic copies that ranged from 8.0 × 10(3 )to 8.0 × 10(9 )in the samples. The main clinical symptom of patients who were positive for HBoV DNA was a pneumonia-like syndrome represented by high fever and cough. Our results suggest that HBoV may be an important etiological agent of LRTI in children in China.",2007 Jan 31,"['Lin, Feng', 'Zeng, Aiping', 'Yang, Ningmin', 'Lin, Haiyan', 'Yang, En', 'Wang, Shengqi', 'Pintel, David', 'Qiu, Jianming']",Infect Agent Cancer,,,True
5c29db6b02088e3b38e416bf32f6a02dbcf9cdf8,PMC,"A perspective on microarrays: current applications, pitfalls, and potential uses",http://dx.doi.org/10.1186/1475-2859-6-4,PMC1796898,17254338,CC BY,"With advances in robotics, computational capabilities, and the fabrication of high quality glass slides coinciding with increased genomic information being available on public databases, microarray technology is increasingly being used in laboratories around the world. In fact, fields as varied as: toxicology, evolutionary biology, drug development and production, disease characterization, diagnostics development, cellular physiology and stress responses, and forensics have benefiting from its use. However, for many researchers not familiar with microarrays, current articles and reviews often address neither the fundamental principles behind the technology nor the proper designing of experiments. Although, microarray technology is relatively simple, conceptually, its practice does require careful planning and detailed understanding of the limitations inherently present. Without these considerations, it can be exceedingly difficult to ascertain valuable information from microarray data. Therefore, this text aims to outline key features in microarray technology, paying particular attention to current applications as outlined in recent publications, experimental design, statistical methods, and potential uses. Furthermore, this review is not meant to be comprehensive, but rather substantive; highlighting important concepts and detailing steps necessary to conduct and interpret microarray experiments. Collectively, the information included in this text will highlight the versatility of microarray technology and provide a glimpse of what the future may hold.",2007 Jan 25,"['Jaluria, Pratik', 'Konstantopoulos, Konstantinos', 'Betenbaugh, Michael', 'Shiloach, Joseph']",Microb Cell Fact,,,True
ab40400780c96601bae9d2f4d1c317dc3322f865,PMC,Characterization of a Structural Intermediate of Flavivirus Membrane Fusion,http://dx.doi.org/10.1371/journal.ppat.0030020,PMC1797619,17305426,CC BY,"Viral membrane fusion proceeds through a sequence of steps that are driven by triggered conformational changes of viral envelope glycoproteins, so-called fusion proteins. Although high-resolution structural snapshots of viral fusion proteins in their prefusion and postfusion conformations are available, it has been difficult to define intermediate structures of the fusion pathway because of their transient nature. Flaviviruses possess a class II viral fusion protein (E) mediating fusion at acidic pH that is converted from a dimer to a trimer with a hairpin-like structure during the fusion process. Here we show for tick-borne encephalitis virus that exposure of virions to alkaline instead of acidic pH traps the particles in an intermediate conformation in which the E dimers dissociate and interact with target membranes via the fusion peptide without proceeding to the merger of the membranes. Further treatment to low pH, however, leads to fusion, suggesting that these monomers correspond to an as-yet-elusive intermediate required to convert the prefusion dimer into the postfusion trimer. Thus, the use of nonphysiological conditions allows a dissection of the flavivirus fusion process and the identification of two separate steps, in which membrane insertion of multiple copies of E monomers precedes the formation of hairpin-like trimers. This sequence of events provides important new insights for understanding the dynamic process of viral membrane fusion.",2007 Feb 16,"['Stiasny, Karin', 'Kössl, Christian', 'Lepault, Jean', 'Rey, Félix A', 'Heinz, Franz X']",PLoS Pathog,,,True
78b25bce9665a46183274a25151de342c9799ef3,PMC,Appropriate 'housekeeping' genes for use in expression profiling the effects of environmental estrogens in fish,http://dx.doi.org/10.1186/1471-2199-8-10,PMC1802086,17288598,CC BY,"BACKGROUND: Attempts to develop a mechanistic understanding of the effects of environmental estrogens on fish are increasingly conducted at the level of gene expression. Appropriate application of real-time PCR in such studies requires the use of a stably expressed 'housekeeping' gene as an internal control to normalize for differences in the amount of starting template between samples. RESULTS: We sought to identify appropriate genes for use as internal controls in experimental treatments with estrogen by analyzing the expression of eight functionally distinct 'housekeeping' genes (18S ribosomal RNA [18S rRNA], ribosomal protein l8 [rpl8], elongation factor 1 alpha [ef1a], glucose-6-phosphate dehydrogenase [g6pd], beta actin [bactin], glyceraldehyde-3-phosphate dehydrogenase [gapdh], hypoxanthine phosphoribosyltransferase 1 [hprt1], and tata box binding protein [tbp]) following exposure to the environmental estrogen, 17α-ethinylestradiol (EE(2)), in the fathead minnow (Pimephales promelas). Exposure to 10 ng/L EE(2 )for 21 days down-regulated the expression of ef1a, g6pd, bactin and gapdh in the liver, and bactin and gapdh in the gonad. Some of these effects were gender-specific, with bactin in the liver and gapdh in the gonad down-regulated by EE(2 )in males only. Furthermore, when ef1a, g6pd, bactin or gapdh were used for normalization, the hepatic expression of two genes of interest, vitellogenin (vtg) and cytochrome P450 1A (cyp1a) following exposure to EE(2 )was overestimated. CONCLUSION: Based on the data presented, we recommend 18S rRNA, rpl8, hprt1 and/or tbp, but not ef1a, g6pd, bactin and/or gapdh, as likely appropriate internal controls in real-time PCR studies of estrogens effects in fish. Our studies show that pre-validation of control genes considering the scope and nature of the experiments to be performed, including both gender and tissue type, is critical for accurate assessments of the effects of environmental estrogens on gene expression in fish.",2007 Feb 8,"['Filby, Amy L', 'Tyler, Charles R']",BMC Mol Biol,,,True
6ac1ceb6e591c8901e4cc265fcba2d9727607942,PMC,Appropriate 'housekeeping' genes for use in expression profiling the effects of environmental estrogens in fish,http://dx.doi.org/10.1186/1471-2199-8-10,PMC1802086,17288598,CC BY,"BACKGROUND: Attempts to develop a mechanistic understanding of the effects of environmental estrogens on fish are increasingly conducted at the level of gene expression. Appropriate application of real-time PCR in such studies requires the use of a stably expressed 'housekeeping' gene as an internal control to normalize for differences in the amount of starting template between samples. RESULTS: We sought to identify appropriate genes for use as internal controls in experimental treatments with estrogen by analyzing the expression of eight functionally distinct 'housekeeping' genes (18S ribosomal RNA [18S rRNA], ribosomal protein l8 [rpl8], elongation factor 1 alpha [ef1a], glucose-6-phosphate dehydrogenase [g6pd], beta actin [bactin], glyceraldehyde-3-phosphate dehydrogenase [gapdh], hypoxanthine phosphoribosyltransferase 1 [hprt1], and tata box binding protein [tbp]) following exposure to the environmental estrogen, 17α-ethinylestradiol (EE(2)), in the fathead minnow (Pimephales promelas). Exposure to 10 ng/L EE(2 )for 21 days down-regulated the expression of ef1a, g6pd, bactin and gapdh in the liver, and bactin and gapdh in the gonad. Some of these effects were gender-specific, with bactin in the liver and gapdh in the gonad down-regulated by EE(2 )in males only. Furthermore, when ef1a, g6pd, bactin or gapdh were used for normalization, the hepatic expression of two genes of interest, vitellogenin (vtg) and cytochrome P450 1A (cyp1a) following exposure to EE(2 )was overestimated. CONCLUSION: Based on the data presented, we recommend 18S rRNA, rpl8, hprt1 and/or tbp, but not ef1a, g6pd, bactin and/or gapdh, as likely appropriate internal controls in real-time PCR studies of estrogens effects in fish. Our studies show that pre-validation of control genes considering the scope and nature of the experiments to be performed, including both gender and tissue type, is critical for accurate assessments of the effects of environmental estrogens on gene expression in fish.",2007 Feb 8,"['Filby, Amy L', 'Tyler, Charles R']",BMC Mol Biol,,,False
9c8db583cc30937e746619bc3ffeda877f2a6369,PMC,Appropriate 'housekeeping' genes for use in expression profiling the effects of environmental estrogens in fish,http://dx.doi.org/10.1186/1471-2199-8-10,PMC1802086,17288598,CC BY,"BACKGROUND: Attempts to develop a mechanistic understanding of the effects of environmental estrogens on fish are increasingly conducted at the level of gene expression. Appropriate application of real-time PCR in such studies requires the use of a stably expressed 'housekeeping' gene as an internal control to normalize for differences in the amount of starting template between samples. RESULTS: We sought to identify appropriate genes for use as internal controls in experimental treatments with estrogen by analyzing the expression of eight functionally distinct 'housekeeping' genes (18S ribosomal RNA [18S rRNA], ribosomal protein l8 [rpl8], elongation factor 1 alpha [ef1a], glucose-6-phosphate dehydrogenase [g6pd], beta actin [bactin], glyceraldehyde-3-phosphate dehydrogenase [gapdh], hypoxanthine phosphoribosyltransferase 1 [hprt1], and tata box binding protein [tbp]) following exposure to the environmental estrogen, 17α-ethinylestradiol (EE(2)), in the fathead minnow (Pimephales promelas). Exposure to 10 ng/L EE(2 )for 21 days down-regulated the expression of ef1a, g6pd, bactin and gapdh in the liver, and bactin and gapdh in the gonad. Some of these effects were gender-specific, with bactin in the liver and gapdh in the gonad down-regulated by EE(2 )in males only. Furthermore, when ef1a, g6pd, bactin or gapdh were used for normalization, the hepatic expression of two genes of interest, vitellogenin (vtg) and cytochrome P450 1A (cyp1a) following exposure to EE(2 )was overestimated. CONCLUSION: Based on the data presented, we recommend 18S rRNA, rpl8, hprt1 and/or tbp, but not ef1a, g6pd, bactin and/or gapdh, as likely appropriate internal controls in real-time PCR studies of estrogens effects in fish. Our studies show that pre-validation of control genes considering the scope and nature of the experiments to be performed, including both gender and tissue type, is critical for accurate assessments of the effects of environmental estrogens on gene expression in fish.",2007 Feb 8,"['Filby, Amy L', 'Tyler, Charles R']",BMC Mol Biol,,,False
af3a11d67c66163d0c0fc185b497e21e55765047,PMC,Correction: Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants,http://dx.doi.org/10.1371/journal.pmed.0040080,PMC1808101,,CC BY,,2007 Feb 27,"['Deming, Damon', 'Sheahan, Timothy', 'Heise, Mark', 'Yount, Boyd', 'Davis, Nancy', 'Sims, Amy', 'Suthar, Mehul', 'Harkema, Jack', 'Whitmore, Alan', 'Pickles, Raymond', 'West, Ande', 'Donaldson, Eric', 'Curtis, Kristopher', 'Johnston, Robert', 'Baric, Ralph']",PLoS Med,,,False
e39c8a18a3d59b83951c4ebc331c17a54e6dacab,PMC,Pathogeneses of respiratory infections with virulent and attenuated vaccinia viruses,http://dx.doi.org/10.1186/1743-422X-4-22,PMC1810241,17326843,CC BY,"BACKGROUND: Respiratory infection with the neurovirulent vaccinia virus (VV) strain Western Reserve (WR) results in an acute infection of the lung followed by dissemination of the virus to other organs and causes lethality in mice. The mechanisms of lethality are not well-understood. In this study, we analyzed virus replication and host immune responses after intranasal infection with lethal and non-lethal doses of VV using the WR strain and the less virulent Wyeth strain. RESULTS: The WR strain replicated more vigorously in the lung and in the brain than the Wyeth strain. There were, however, no differences between the virus titers in the brains of mice infected with the higher lethal dose and the lower non-lethal dose of WR strain, suggesting that the amount of virus replication in the brain is unlikely to be the sole determining factor of lethality. The WR strain grew better in primary mouse lung cells than the Wyeth strain. Lethal infection with WR strain was associated with a reduced number of lymphocytes and an altered phenotype of the T cells in the lung compared to non-lethal infections with the WR or Wyeth strains. Severe thymus atrophy with a reduction of CD4 and CD8 double positive T cells was also observed in the lethal infection. CONCLUSION: These results suggest that the lethality induced by intranasal infection with a high dose of the WR strain is caused by the higher replication of virus in lung cells and immune suppression during the early phase of the infection, resulting in uncontrolled virus replication in the lung.",2007 Feb 27,"['Hayasaka, Daisuke', 'Ennis, Francis A', 'Terajima, Masanori']",Virol J,,,True
2cb893552a3e4a8aa105a96476b02c16bf7bef42,PMC,Feline aminopeptidase N is not a functional receptor for avian infectious bronchitis virus,http://dx.doi.org/10.1186/1743-422X-4-20,PMC1810517,17324273,CC BY,"BACKGROUND: Coronaviruses are an important cause of infectious diseases in humans, including severe acute respiratory syndrome (SARS), and have the continued potential for emergence from animal species. A major factor in the host range of a coronavirus is its receptor utilization on host cells. In many cases, coronavirus-receptor interactions are well understood. However, a notable exception is the receptor utilization by group 3 coronaviruses, including avian infectious bronchitis virus (IBV). Feline aminopeptidase N (fAPN) serves as a functional receptor for most group 1 coronaviruses including feline infectious peritonitis virus (FIPV), canine coronavirus, transmissible gastroenteritis virus (TGEV), and human coronavirus 229E (HCoV-229E). A recent report has also suggested a role for fAPN during IBV entry (Miguel B, Pharr GT, Wang C: The role of feline aminopeptidase N as a receptor for infectious bronchitis virus. Brief review. Arch Virol 2002, 147:2047–2056. RESULTS: Here we show that, whereas both transient transfection and constitutive expression of fAPN on BHK-21 cells can rescue FIPV and TGEV infection in non-permissive BHK cells, fAPN expression does not rescue infection by the prototype IBV strain Mass41. To account for the previous suggestion that fAPN could serve as an IBV receptor, we show that feline cells can be infected with the prototype strain of IBV (Mass 41), but with low susceptibility compared to primary chick kidney cells. We also show that BHK-21 cells are slightly susceptible to certain IBV strains, including Ark99, Ark_DPI, CA99, and Iowa97 (<0.01% efficiency), but this level of infection is not increased by fAPN expression. CONCLUSION: We conclude that fAPN is not a functional receptor for IBV, the identity of which is currently under investigation.",2007 Feb 26,"['Chu, Victor C', 'McElroy, Lisa J', 'Aronson, Jed M', 'Oura, Trisha J', 'Harbison, Carole E', 'Bauman, Beverley E', 'Whittaker, Gary R']",Virol J,,,True
38771dc09043758e9f76b1c8746495874d2a41bc,PMC,Different rates of (non-)synonymous mutations in astrovirus genes; correlation with gene function,http://dx.doi.org/10.1186/1743-422X-4-25,PMC1828050,17343744,CC BY,"BACKGROUND: Complete genome sequences of the Astroviridae include human, non-human mammalian and avian species. A consensus topology of astroviruses has been derived from nucleotide substitutions in the full-length genomes and from non-synonymous nucleotide substitutions in each of the three ORFs. Analyses of synonymous substitutions displayed a loss of tree structure, suggesting either saturation of the substitution model or a deviant pattern of synonymous substitutions in certain virus species. RESULTS: We analyzed the complete Astroviridae family for the inference of adaptive molecular evolution at sites and in branches. High rates of synonymous mutations are observed among the non-human virus species. Deviant patterns of synonymous substitutions are found in the capsid structural genes. Purifying selection is a dominant force among all astrovirus genes and only few codon sites showed values for the dN/dS ratio that may indicate site-specific molecular adaptation during virus evolution. One of these sites is the glycine residue of a RGD motif in ORF2 of human astrovirus serotype 1. RGD or similar integrin recognition motifs are present in nearly all astrovirus species. CONCLUSION: Phylogenetic analysis directed by maximum likelihood approximation allows the inclusion of significantly more evolutionary history and thereby, improves the estimation of dN and dS. Sites with enhanced values for dN/dS are prominent at domains in charge of environmental communication (f.i. VP27 and domain 4 in ORF1a) more than at domains dedicated to intrinsic virus functions (f.i. VP34 and ORF1b (the virus polymerase)). Integrin recognition may play a key role in astrovirus to target cell attachment.",2007 Mar 7,"['van Hemert, Formijn J', 'Lukashov, Vladimir V', 'Berkhout, Ben']",Virol J,,,True
d882f79283751d6c7f2e48cb991ee8abbcd913ae,PMC,The Transmissibility of Highly Pathogenic Avian Influenza in Commercial Poultry in Industrialised Countries,http://dx.doi.org/10.1371/journal.pone.0000349,PMC1831494,17406673,CC BY,"BACKGROUND: With the increased occurrence of outbreaks of H5N1 worldwide there is concern that the virus could enter commercial poultry farms with severe economic consequences. METHODOLOGY/PRINCIPAL FINDINGS: We analyse data from four recent outbreaks of highly pathogenic avian influenza (HPAI) in commercial poultry to estimate the farm-to-farm reproductive number for HPAI. The reproductive number is a key measure of the transmissibility of HPAI at the farm level because it can be used to evaluate the effectiveness of the control measures. In these outbreaks the mean farm-to-farm reproductive number prior to controls ranged from 1.1 to 2.4, with the maximum farm-based reproductive number in the range 2.2 to 3.2. Enhanced bio-security, movement restrictions and prompt isolation of the infected farms in all four outbreaks substantially reduced the reproductive number, but it remained close to the threshold value 1 necessary to ensure the disease will be eradicated. CONCLUSIONS/SIGNIFICANCE: Our results show that depending on the particular situation in which an outbreak of avian influenza occurs, current controls might not be enough to eradicate the disease, and therefore a close monitoring of the outbreak is required. The method we used for estimating the reproductive number is straightforward to implement and can be used in real-time. It therefore can be a useful tool to inform policy decisions.",2007 Apr 4,"['Garske, Tini', 'Clarke, Paul', 'Ghani, Azra C.']",PLoS One,,,True
78942768be77bf181f97de25fb67e8582d884e51,PMC,The Transmissibility of Highly Pathogenic Avian Influenza in Commercial Poultry in Industrialised Countries,http://dx.doi.org/10.1371/journal.pone.0000349,PMC1831494,17406673,CC BY,"BACKGROUND: With the increased occurrence of outbreaks of H5N1 worldwide there is concern that the virus could enter commercial poultry farms with severe economic consequences. METHODOLOGY/PRINCIPAL FINDINGS: We analyse data from four recent outbreaks of highly pathogenic avian influenza (HPAI) in commercial poultry to estimate the farm-to-farm reproductive number for HPAI. The reproductive number is a key measure of the transmissibility of HPAI at the farm level because it can be used to evaluate the effectiveness of the control measures. In these outbreaks the mean farm-to-farm reproductive number prior to controls ranged from 1.1 to 2.4, with the maximum farm-based reproductive number in the range 2.2 to 3.2. Enhanced bio-security, movement restrictions and prompt isolation of the infected farms in all four outbreaks substantially reduced the reproductive number, but it remained close to the threshold value 1 necessary to ensure the disease will be eradicated. CONCLUSIONS/SIGNIFICANCE: Our results show that depending on the particular situation in which an outbreak of avian influenza occurs, current controls might not be enough to eradicate the disease, and therefore a close monitoring of the outbreak is required. The method we used for estimating the reproductive number is straightforward to implement and can be used in real-time. It therefore can be a useful tool to inform policy decisions.",2007 Apr 4,"['Garske, Tini', 'Clarke, Paul', 'Ghani, Azra C.']",PLoS One,,,False
8b4eff9d625d8aa4d5795f4b07a9df388d2acfab,PMC,"Ethnoveterinary medicines used for ruminants in British Columbia, Canada",http://dx.doi.org/10.1186/1746-4269-3-11,PMC1831764,17324258,CC BY,"BACKGROUND: The use of medicinal plants is an option for livestock farmers who are not allowed to use allopathic drugs under certified organic programs or cannot afford to use allopathic drugs for minor health problems of livestock. METHODS: In 2003 we conducted semi-structured interviews with 60 participants obtained using a purposive sample. Medicinal plants are used to treat a range of conditions. A draft manual prepared from the data was then evaluated by participants at a participatory workshop. RESULTS: There are 128 plants used for ruminant health and diets, representing several plant families. The following plants are used for abscesses: Berberis aquifolium/Mahonia aquifolium Echinacea purpurea, Symphytum officinale, Bovista pila, Bovista plumbea, Achillea millefolium and Usnea longissima. Curcuma longa L., Salix scouleriana and Salix lucida are used for caprine arthritis and caprine arthritis encephalitis.Euphrasia officinalis and Matricaria chamomilla are used for eye problems. Wounds and injuries are treated with Bovista spp., Usnea longissima, Calendula officinalis, Arnica sp., Malva sp., Prunella vulgaris, Echinacea purpurea, Berberis aquifolium/Mahonia aquifolium, Achillea millefolium, Capsella bursa-pastoris, Hypericum perforatum, Lavandula officinalis, Symphytum officinale and Curcuma longa. Syzygium aromaticum and Pseudotsuga menziesii are used for coccidiosis. The following plants are used for diarrhea and scours: Plantago major, Calendula officinalis, Urtica dioica, Symphytum officinale, Pinus ponderosa, Potentilla pacifica, Althaea officinalis, Anethum graveolens, Salix alba and Ulmus fulva. Mastitis is treated with Achillea millefolium, Arctium lappa, Salix alba, Teucrium scorodonia and Galium aparine. Anethum graveolens and Rubus sp., are given for increased milk production.Taraxacum officinale, Zea mays, and Symphytum officinale are used for udder edema. Ketosis is treated with Gaultheria shallon, Vaccinium sp., and Symphytum officinale. Hedera helix and Alchemilla vulgaris are fed for retained placenta. CONCLUSION: Some of the plants showing high levels of validity were Hedera helix for retained placenta and Euphrasia officinalis for eye problems. Plants with high validity for wounds and injuries included Hypericum perforatum, Malva parviflora and Prunella vulgaris. Treatments with high validity against endoparasites included those with Juniperus communis and Pinus ponderosa. Anxiety and pain are well treated with Melissa officinalis and Nepeta caesarea.",2007 Feb 26,"['Lans, Cheryl', 'Turner, Nancy', 'Khan, Tonya', 'Brauer, Gerhard', 'Boepple, Willi']",J Ethnobiol Ethnomed,,,True
f3f471d10a36a7a28e9050c10bd4dfd680cba17b,PMC,The influenza pandemic preparedness planning tool InfluSim,http://dx.doi.org/10.1186/1471-2334-7-17,PMC1832202,17355639,CC BY,"BACKGROUND: Planning public health responses against pandemic influenza relies on predictive models by which the impact of different intervention strategies can be evaluated. Research has to date rather focused on producing predictions for certain localities or under specific conditions, than on designing a publicly available planning tool which can be applied by public health administrations. Here, we provide such a tool which is reproducible by an explicitly formulated structure and designed to operate with an optimal combination of the competing requirements of precision, realism and generality. RESULTS: InfluSim is a deterministic compartment model based on a system of over 1,000 differential equations which extend the classic SEIR model by clinical and demographic parameters relevant for pandemic preparedness planning. It allows for producing time courses and cumulative numbers of influenza cases, outpatient visits, applied antiviral treatment doses, hospitalizations, deaths and work days lost due to sickness, all of which may be associated with economic aspects. The software is programmed in Java, operates platform independent and can be executed on regular desktop computers. CONCLUSION: InfluSim is an online available software which efficiently assists public health planners in designing optimal interventions against pandemic influenza. It can reproduce the infection dynamics of pandemic influenza like complex computer simulations while offering at the same time reproducibility, higher computational performance and better operability.",2007 Mar 13,"['Eichner, Martin', 'Schwehm, Markus', 'Duerr, Hans-Peter', 'Brockmann, Stefan O']",BMC Infect Dis,,,True
aa8471e98490ab2c5a2dabea9a4d2f66c9427bfb,PMC,Whole genome molecular phylogeny of large dsDNA viruses using composition vector method,http://dx.doi.org/10.1186/1471-2148-7-41,PMC1839080,17359548,CC BY,"BACKGROUND: One important mechanism by which large DNA viruses increase their genome size is the addition of modules acquired from other viruses, host genomes or gene duplications. Phylogenetic analysis of large DNA viruses, especially using methods based on alignment, is often difficult due to the presence of horizontal gene transfer events. The recent composition vector approach, not sensitive to such events, is applied here to reconstruct the phylogeny of 124 large DNA viruses. RESULTS: The results are mostly consistent with the biologist's systematics with only a few outliers and can also provide some information for those unclassified viruses and cladistic relationships of several families. CONCLUSION: With composition vector approach we obtained the phylogenetic tree of large DNA viruses, which not only give results comparable to biologist's systematics but also provide a new way for recovering the phylogeny of viruses.",2007 Mar 15,"['Gao, Lei', 'Qi, Ji']",BMC Evol Biol,,,True
f592542c73a8294125b53d9eeef9a61cfcd9b1a3,PMC,Conserved aspartic acid 233 and alanine 231 are not required for poliovirus polymerase function in replicons,http://dx.doi.org/10.1186/1743-422X-4-28,PMC1839082,17352827,CC BY,"Nucleic acid polymerases have similar structures and motifs. The function of an aspartic acid (conserved in all classes of nucleic acid polymerases) in motif A remains poorly understood in RNA-dependent RNA polymerases. We mutated this residue to alanine in a poliovirus replicon. The resulting mutant could still replicate, although at a reduced level. In addition, mutation A231C (also in motif A) yielded high levels of replication. Taken together these results show that poliovirus polymerase conserved residues D233 and A231 are not essential to poliovirus replicon function.",2007 Mar 12,"['Freistadt, Marion S', 'Eberle, Karen E']",Virol J,,,True
b7c8e73cf095e30552a32cea04a398331c55ab41,PMC,Anticipated and current preventive behaviors in response to an anticipated human-to-human H5N1 epidemic in the Hong Kong Chinese general population,http://dx.doi.org/10.1186/1471-2334-7-18,PMC1845150,17359545,CC BY,"BACKGROUND: The prevalence of self-reported preventive behaviors in response to an anticipated local human-to-human H5N1 transmission outbreak and factors associated with such behaviors have not been examined. METHODS: A random, anonymous, cross-sectional telephone survey of 503 Hong Kong Chinese adults. RESULTS: The public in Hong Kong is likely to adopt self-protective behaviors (e.g., wearing face mask in public venues (73.8%), increasing the frequency of handwashing (86.7%)) and behaviors that protect others (e.g., wearing face masks when experiencing influenza-like illness (ILI, 92.4%), immediately seeking medical consultation (94.2%), making declarations when crossing the border with ILI (87.1%), complying to quarantine policies (88.3%)). Multivariate analyses indicated that factors related to age, full-time employment, perceived susceptibility, perceived efficacy of preventive measures, perceived higher fatality as compared to SARS, perceived chance of a major local outbreak, and being worried about self/family members contracting the virus were significantly associated with the inclination to adopt self-protective measures. Similar analyses showed that education level, variables related to perceived efficacy, perceived major local outbreak and such were significantly associated with various behaviors directed towards protecting others. CONCLUSION: In the event of a human-to-human H5N1 outbreak, the public in Hong Kong is likely to adopt preventive measures that may help contain the spread of the virus in the community.",2007 Mar 15,"['Lau, Joseph TF', 'Kim, Jean H', 'Tsui, Hi Yi', 'Griffiths, Sian']",BMC Infect Dis,,,True
4baa61e791ff5aa90affac055aee043503472aaa,PMC,"Biodiversity, traditional medicine and public health: where do they meet?",http://dx.doi.org/10.1186/1746-4269-3-14,PMC1847427,17376227,CC BY,"Given the increased use of traditional medicines, possibilities that would ensure its successful integration into a public health framework should be explored. This paper discusses some of the links between biodiversity and traditional medicine, and addresses their implications to public health. We explore the importance of biodiversity and ecosystem services to global and human health, the risks which human impacts on ecosystems and biodiversity present to human health and welfare.",2007 Mar 21,"['Alves, Rômulo RN', 'Rosa, Ierecê ML']",J Ethnobiol Ethnomed,,,True
0094b25e2500306fadbdfb41d520f2970bb086d3,PMC,Sex- and age-dependent association of SLC11A1 polymorphisms with tuberculosis in Chinese: a case control study,http://dx.doi.org/10.1186/1471-2334-7-19,PMC1847518,17371589,CC BY,"BACKGROUND: Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB. METHODS: A case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex- and age-matched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products. RESULTS: Statistically significant differences in allele (P = 0.0165, OR = 1.51) and genotype (P = 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of the SLC11A1 locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P = 0.0049, OR = 2.54) and genotype (P = 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age ≤65 years) for both allele (P = 0.0047, OR = 2.52) and genotype (P = 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older age group. No significant differences were found for the other markers (one SLC11A1 marker and one IL8RB marker) either. CONCLUSION: This study confirmed the association between SLC11A1 and TB susceptibility and demonstrated for the first time that the association was restricted to females and the young age group.",2007 Mar 19,"['Leung, Kim Hung', 'Yip, Shea Ping', 'Wong, Wa Sang', 'Yiu, Lap San', 'Chan, Kam Keung', 'Lai, Wai Man', 'Chow, Eudora YD', 'Lin, Che Kit', 'Yam, Wing Cheong', 'Chan, Kin Sang']",BMC Infect Dis,,,True
305cf1019ca9c81126b2e527fedf79969c2c522f,PMC,"ElaD, a Deubiquitinating Protease Expressed by E. coli",http://dx.doi.org/10.1371/journal.pone.0000381,PMC1847702,17440617,CC BY,"BACKGROUND: Ubiquitin and ubiquitin-like proteins (Ubl) are designed to modify polypeptides in eukaryotes. Covalent binding of ubiquitin or Ubls to substrate proteins can be reversed by specific hydrolases. One particular set of cysteine proteases, the CE clan, which targets ubiquitin and Ubls, has homologs in eukaryotes, prokaryotes, and viruses. FINDINGS: We have cloned and analyzed the E. coli protein elaD, which is distantly related to eukaryotic CE clan members of the ULP/SENP protease family that are specific for SUMO and Nedd8. Previously misannotated as a putative sulfatase/phosphatase, elaD is an efficient and specific deubiquitinating enzyme in vitro. Interestingly, elaD is present in all intestinal pathogenic E. coli strains, but conspicuously absent from extraintestinal pathogenic strains (ExPECs). Further homologs of this protease can be found in Acanthamoeba Polyphaga Mimivirus, and in Alpha-, Beta-and Gammaproteobacteria. CONCLUSION: The expression of ULP/SENP-related hydrolases in bacteria therefore extends to plant pathogens and medically relevant strains of Escherichia coli, Legionella pneumophila, Rickettsiae, Chlamydiae, and Salmonellae, in which the elaD ortholog sseL has recently been identified as a virulence factor with deubiquitinating activity. As a counterpoint, our phylogenetic and functional examination reveals that ancient eukaryotic ULP/SENP proteases also have the potential of ubiquitin-specific hydrolysis, suggesting an early common origin of this peptidase clan.",2007 Apr 18,"['Catic, André', 'Misaghi, Shahram', 'Korbel, Gregory A.', 'Ploegh, Hidde L.']",PLoS One,,,True
71f2f3ffaa761b9d7e50b3d22eb0aacb78728bd9,PMC,Using patient-collected clinical samples and sera to detect and quantify the severe acute respiratory syndrome coronavirus (SARS-CoV),http://dx.doi.org/10.1186/1743-422X-4-32,PMC1851004,17386116,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS) caused a large outbreak of pneumonia in Beijing, China, in 2003. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect and quantify SARS-CoV in 934 sera and self-collected throat washes and fecal samples from 271 patients with laboratory-confirmed SARS managed at a single institution. RESULTS: SARS-CoV detection rates in sera were highest in the first 9 days of illness, whereas detection was highest in throat washes 5–14 days after onset of symptoms. The highest SARS-CoV RT-PCR rates (70.4–86.3%) and viral loads (log(10 )4.5–6.1) were seen in fecal samples collected 2–4 weeks after the onset of clinical illness. Fecal samples were frequently SARS-CoV RT-PCR positive beyond 40 days, and occasional sera still had SARS-CoV detected after 3 weeks of illness. CONCLUSION: In the context of an extensive outbreak with major pressure on hospital resources, patient self-collected samples are an alternative to nasopharyngeal aspirates for laboratory confirmation of SARS-CoV infection.",2007 Mar 27,"['He, Zhongping', 'Zhuang, Hui', 'Zhao, Chunhui', 'Dong, Qingming', 'Peng, Guoai', 'Dwyer, Dominic E']",Virol J,,,True
ee8dca216514deeed4c9415bc2ad8a78dc3d9670,PMC,A focus reduction neutralization assay for hepatitis C virus neutralizing antibodies,http://dx.doi.org/10.1186/1743-422X-4-35,PMC1852297,17397531,CC BY,"BACKGROUND/AIM: The role of humoral immunity in hepatitis C virus (HCV) infection is poorly understood. Nevertheless, there is increasing interest in characterizing the neutralizing antibodies in the serum of HCV-infected patients. Focus reduction assays have been widely used to evaluate neutralizing antibody responses against a range of non-cytopathic viruses. Based on the recent development of a HCV cell culture system using the genotype 2 JFH-1-strain, we developed a focus reduction assay for HCV-neutralizing antibodies. METHODS: The focus reduction assay was based on a standard microneutralization assay in which immunostained foci on tissue culture plates are counted. The neutralizing anti-HCV antibodies titers of purified serum immunoglobulin samples from seventy-seven individuals were determined using a 50% focus reduction neutralization assay. Each titer was determined as the log value of the reciprocal antibody dilution that reduced the number of viral foci by 50%. IgG antibodies were first purified from each serum in order to avoid the facilitating effect of HDL on HCV entry. RESULTS: The assay's cut-off using an ELISA and RNA HCV-negative samples was found to be 1.25 log, corresponding to a dilution of 1:18. The assay was compared with a commercial HCV ELISA and exhibited specificity and sensitivity values of 100% and 96.5%, respectively, and good reproducibility (with intra-assay and inter-assay coefficients of variation of 6.7% and 12.6%, respectively). The assay did not show any cross-reactivity with anti-HIV, anti-HBs or heterophile antibody-positive samples. The neutralizing antibodies titers were 2.13 log (1:134) for homologous samples from HCV genotype 2 infected patients harboring the same genotype as JFH-1 and 1.93 log (1:85) for heterologous samples from patients infected by genotypes other than type 2. These results confirm the presence of broadly cross-neutralizing antibodies already reported using the HCV pseudoparticles system. CONCLUSION: This study presents a simple, specific and reproducible cell culture-based assay for determination of HCV-neutralizing antibodies in human sera. The assay should be an important tool for gauging the relationship between the neutralizing antibodies response and viral load kinetics in acutely or chronically infected patients and for investigating the possible eradication or prevention of HCV infection by neutralizing antibodies.",2007 Mar 30,"['Fournier, Carole', 'Duverlie, Gilles', 'François, Catherine', 'Schnuriger, Aurelie', 'Dedeurwaerder, Sarah', 'Brochot, Etienne', 'Capron, Dominique', 'Wychowski, Czeslaw', 'Thibault, Vincent', 'Castelain, Sandrine']",Virol J,,,True
58f68e82f134cf3549778fca86251ee61975b596,PMC,High level expression of soluble glycoproteins in the allantoic fluid of embryonated chicken eggs using a Sendai virus minigenome system,http://dx.doi.org/10.1186/1472-6750-7-17,PMC1852797,17411439,CC BY,"BACKGROUND: Embryonated chicken eggs have been used since the mid-20th century to grow a wide range of animal viruses to high titers. However, eggs have found so far only limited use in the production of recombinant proteins. We now describe a system, based on a Sendai virus minigenome, to produce large amounts of heterologous viral glycoproteins in the allantoic cavity of embryonated eggs. RESULTS: Soluble forms of human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) fusion (F) proteins, devoid of their transmembrane and cytoplasmic domains, were produced in allantoic fluids using the Sendai minigenome system. The first step was rescuing in cell cultures Sendai virus minigenomes encoding the proteins of interest, with the help of wild type Sendai virus. The second step was propagating such recombinant defective viruses, together with the helper virus, in the allantoic cavity of chicken embryonated eggs, and passage to optimize protein production. When compared with the production of the same proteins in the culture supernatant of cells infected with vaccinia recombinants, the yield in the allantoic fluid was 5–10 fold higher. Mutant forms of these soluble proteins were easily constructed by site-directed mutagenesis and expressed in eggs using the same approach. CONCLUSION: The simplicity and economy of the Sendai minigenome system, together with the high yield achieved in the allantoic fluid of eggs, makes it an attractive method to express soluble glycoproteins aimed for structural studies.",2007 Apr 5,"['Corral, Teresa', 'Ver, Lorena S', 'Mottet, Geneviève', 'Cano, Olga', 'García-Barreno, Blanca', 'Calder, Lesley J', 'Skehel, John J', 'Roux, Laurent', 'Melero, José A']",BMC Biotechnol,,,True
4e0851aa892c56090edbc47e9506313d2a1b20e0,PMC,Incorporating indel information into phylogeny estimation for rapidly emerging pathogens,http://dx.doi.org/10.1186/1471-2148-7-40,PMC1853084,17359539,CC BY,"BACKGROUND: Phylogenies of rapidly evolving pathogens can be difficult to resolve because of the small number of substitutions that accumulate in the short times since divergence. To improve resolution of such phylogenies we propose using insertion and deletion (indel) information in addition to substitution information. We accomplish this through joint estimation of alignment and phylogeny in a Bayesian framework, drawing inference using Markov chain Monte Carlo. Joint estimation of alignment and phylogeny sidesteps biases that stem from conditioning on a single alignment by taking into account the ensemble of near-optimal alignments. RESULTS: We introduce a novel Markov chain transition kernel that improves computational efficiency by proposing non-local topology rearrangements and by block sampling alignment and topology parameters. In addition, we extend our previous indel model to increase biological realism by placing indels preferentially on longer branches. We demonstrate the ability of indel information to increase phylogenetic resolution in examples drawn from within-host viral sequence samples. We also demonstrate the importance of taking alignment uncertainty into account when using such information. Finally, we show that codon-based substitution models can significantly affect alignment quality and phylogenetic inference by unrealistically forcing indels to begin and end between codons. CONCLUSION: These results indicate that indel information can improve phylogenetic resolution of recently diverged pathogens and that alignment uncertainty should be considered in such analyses.",2007 Mar 14,"['Redelings, Benjamin D', 'Suchard, Marc A']",BMC Evol Biol,,,True
0fcfac3230a7ab2f3b600fd06eebdf084066d01b,PMC,"Application of Broad-Spectrum, Sequence-Based Pathogen Identification in an Urban Population",http://dx.doi.org/10.1371/journal.pone.0000419,PMC1855431,17502915,CC0,"A broad spectrum detection platform that provides sequence level resolution of target regions would have a significant impact in public health, case management, and means of expanding our understanding of the etiology of diseases. A previously developed respiratory pathogen microarray (RPM v.1) demonstrated the capability of this platform for this purpose. This newly developed RPM v.1 was used to analyze 424 well-characterized nasal wash specimens from patients presenting with febrile respiratory illness in the Washington, D. C. metropolitan region. For each specimen, the RPM v.1 results were compared against composite reference assay (viral and bacterial culture and, where appropriate, RT-PCR/PCR) results. Across this panel, the RPM assay showed ≥98% overall agreement for all the organisms detected compared with reference methods. Additionally, the RPM v.1 results provide sequence information which allowed phylogenetic classification of circulating influenza A viruses in ∼250 clinical specimens, and allowed monitoring the genetic variation as well as antigenic variability prediction. Multiple pathogens (2–4) were detected in 58 specimens (13.7%) with notably increased abundances of respiratory colonizers (esp. S. pneumoniae) during viral infection. This first-ever comparison of a broad-spectrum viral and bacterial identification technology of this type against a large battery of conventional “gold standard” assays confirms the utility of the approach for both medical surveillance and investigations of complex etiologies of illness caused by respiratory co-infections.",2007 May 9,"['Lin, Baochuan', 'Malanoski, Anthony P.', 'Wang, Zheng', 'Blaney, Kate M.', 'Ligler, Adam G.', 'Rowley, Robb K.', 'Hanson, Eric H.', 'von Rosenvinge, Erik', 'Ligler, Frances S.', 'Kusterbeck, Anne W.', 'Metzgar, David', 'Barrozo, Christopher P.', 'Russell, Kevin L.', 'Tibbetts, Clark', 'Schnur, Joel M.', 'Stenger, David A.']",PLoS One,,,True
dc7809e3cbcc5bb53b481641f6796891f4ecedc4,PMC,Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.ppat.0030064,PMC1864993,17480120,CC BY,"We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.",2007 May 4,"['Gaynor, Anne M', 'Nissen, Michael D', 'Whiley, David M', 'Mackay, Ian M', 'Lambert, Stephen B', 'Wu, Guang', 'Brennan, Daniel C', 'Storch, Gregory A', 'Sloots, Theo P', 'Wang, David']",PLoS Pathog,,,True
f12d8e834fd7275d5c656309ff0ac1e2343c68dd,PMC,Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.ppat.0030064,PMC1864993,17480120,CC BY,"We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.",2007 May 4,"['Gaynor, Anne M', 'Nissen, Michael D', 'Whiley, David M', 'Mackay, Ian M', 'Lambert, Stephen B', 'Wu, Guang', 'Brennan, Daniel C', 'Storch, Gregory A', 'Sloots, Theo P', 'Wang, David']",PLoS Pathog,,,False
654bfa151888fd9914a4f78a4980c01b3817c9a4,PMC,Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.ppat.0030064,PMC1864993,17480120,CC BY,"We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.",2007 May 4,"['Gaynor, Anne M', 'Nissen, Michael D', 'Whiley, David M', 'Mackay, Ian M', 'Lambert, Stephen B', 'Wu, Guang', 'Brennan, Daniel C', 'Storch, Gregory A', 'Sloots, Theo P', 'Wang, David']",PLoS Pathog,,,False
4c01a2cce1c31f2f194ea63d3639282f96984c8a,PMC,Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.ppat.0030064,PMC1864993,17480120,CC BY,"We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.",2007 May 4,"['Gaynor, Anne M', 'Nissen, Michael D', 'Whiley, David M', 'Mackay, Ian M', 'Lambert, Stephen B', 'Wu, Guang', 'Brennan, Daniel C', 'Storch, Gregory A', 'Sloots, Theo P', 'Wang, David']",PLoS Pathog,,,False
b199920959658ae175110d31a052db162aaf3d02,PMC,Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.ppat.0030064,PMC1864993,17480120,CC BY,"We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.",2007 May 4,"['Gaynor, Anne M', 'Nissen, Michael D', 'Whiley, David M', 'Mackay, Ian M', 'Lambert, Stephen B', 'Wu, Guang', 'Brennan, Daniel C', 'Storch, Gregory A', 'Sloots, Theo P', 'Wang, David']",PLoS Pathog,,,False
b3f43bc854e6c08a8ce20030be933fe9d08afc41,PMC,Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.ppat.0030064,PMC1864993,17480120,CC BY,"We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.",2007 May 4,"['Gaynor, Anne M', 'Nissen, Michael D', 'Whiley, David M', 'Mackay, Ian M', 'Lambert, Stephen B', 'Wu, Guang', 'Brennan, Daniel C', 'Storch, Gregory A', 'Sloots, Theo P', 'Wang, David']",PLoS Pathog,,,False
8b9c29263c0ecc9a29e8f5ee2a4afa9b95e1a6c9,PMC,Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.ppat.0030064,PMC1864993,17480120,CC BY,"We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.",2007 May 4,"['Gaynor, Anne M', 'Nissen, Michael D', 'Whiley, David M', 'Mackay, Ian M', 'Lambert, Stephen B', 'Wu, Guang', 'Brennan, Daniel C', 'Storch, Gregory A', 'Sloots, Theo P', 'Wang, David']",PLoS Pathog,,,False
6f08b893f2190ac79dbeb85302703bf519037b7b,PMC,"Fellowships, Grants, & Awards",,PMC1867954,,CC0,,2007 May,,Environ Health Perspect,,,True
60081af7cc91d270d05e6cb45285578f86c918fb,PMC,Analysis of Intraviral Protein-Protein Interactions of the SARS Coronavirus ORFeome,http://dx.doi.org/10.1371/journal.pone.0000459,PMC1868897,17520018,CC BY,"The severe acute respiratory syndrome coronavirus (SARS-CoV) genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products. The functions of a large number of viral ORFs are poorly understood or unknown. In order to gain more insight into functions and modes of action and interaction of the different proteins, we cloned the viral ORFeome and performed a genome-wide analysis for intraviral protein interactions and for intracellular localization. 900 pairwise interactions were tested by yeast-two-hybrid matrix analysis, and more than 65 positive non-redundant interactions, including six self interactions, were identified. About 38% of interactions were subsequently confirmed by CoIP in mammalian cells. Nsp2, nsp8 and ORF9b showed a wide range of interactions with other viral proteins. Nsp8 interacts with replicase proteins nsp2, nsp5, nsp6, nsp7, nsp8, nsp9, nsp12, nsp13 and nsp14, indicating a crucial role as a major player within the replication complex machinery. It was shown by others that nsp8 is essential for viral replication in vitro, whereas nsp2 is not. We show that also accessory protein ORF9b does not play a pivotal role for viral replication, as it can be deleted from the virus displaying normal plaque sizes and growth characteristics in Vero cells. However, it can be expected to be important for the virus-host interplay and for pathogenicity, due to its large number of interactions, by enhancing the global stability of the SARS proteome network, or play some unrealized role in regulating protein-protein interactions. The interactions identified provide valuable material for future studies.",2007 May 23,"['von Brunn, Albrecht', 'Teepe, Carola', 'Simpson, Jeremy C.', 'Pepperkok, Rainer', 'Friedel, Caroline C.', 'Zimmer, Ralf', 'Roberts, Rhonda', 'Baric, Ralph', 'Haas, Jürgen']",PLoS One,,,True
435baf47b4f78fc06a8376f451993059407d2972,PMC,Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry,http://dx.doi.org/10.1371/journal.pone.0000489,PMC1876795,17534439,CC0,"BACKGROUND: Effective influenza surveillance requires new methods capable of rapid and inexpensive genomic analysis of evolving viral species for pandemic preparedness, to understand the evolution of circulating viral species, and for vaccine strain selection. We have developed one such approach based on previously described broad-range reverse transcription PCR/electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology. METHODS AND PRINCIPAL FINDINGS: Analysis of base compositions of RT-PCR amplicons from influenza core gene segments (PB1, PB2, PA, M, NS, NP) are used to provide sub-species identification and infer influenza virus H and N subtypes. Using this approach, we detected and correctly identified 92 mammalian and avian influenza isolates, representing 30 different H and N types, including 29 avian H5N1 isolates. Further, direct analysis of 656 human clinical respiratory specimens collected over a seven-year period (1999–2006) showed correct identification of the viral species and subtypes with >97% sensitivity and specificity. Base composition derived clusters inferred from this analysis showed 100% concordance to previously established clades. Ongoing surveillance of samples from the recent influenza virus seasons (2005–2006) showed evidence for emergence and establishment of new genotypes of circulating H3N2 strains worldwide. Mixed viral quasispecies were found in approximately 1% of these recent samples providing a view into viral evolution. CONCLUSION/SIGNIFICANCE: Thus, rapid RT-PCR/ESI-MS analysis can be used to simultaneously identify all species of influenza viruses with clade-level resolution, identify mixed viral populations and monitor global spread and emergence of novel viral genotypes. This high-throughput method promises to become an integral component of influenza surveillance.",2007 May 30,"['Sampath, Rangarajan', 'Russell, Kevin L.', 'Massire, Christian', 'Eshoo, Mark W.', 'Harpin, Vanessa', 'Blyn, Lawrence B.', 'Melton, Rachael', 'Ivy, Cristina', 'Pennella, Thuy', 'Li, Feng', 'Levene, Harold', 'Hall, Thomas A.', 'Libby, Brian', 'Fan, Nancy', 'Walcott, Demetrius J.', 'Ranken, Raymond', 'Pear, Michael', 'Schink, Amy', 'Gutierrez, Jose', 'Drader, Jared', 'Moore, David', 'Metzgar, David', 'Addington, Lynda', 'Rothman, Richard', 'Gaydos, Charlotte A.', 'Yang, Samuel', 'St. George, Kirsten', 'Fuschino, Meghan E.', 'Dean, Amy B.', 'Stallknecht, David E.', 'Goekjian, Ginger', 'Yingst, Samuel', 'Monteville, Marshall', 'Saad, Magdi D.', 'Whitehouse, Chris A.', 'Baldwin, Carson', 'Rudnick, Karl H.', 'Hofstadler, Steven A.', 'Lemon, Stanley M.', 'Ecker, David J.']",PLoS One,,,True
3c0ab78f942980f89e0c14faf2b393328b79f27d,PMC,Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry,http://dx.doi.org/10.1371/journal.pone.0000489,PMC1876795,17534439,CC0,"BACKGROUND: Effective influenza surveillance requires new methods capable of rapid and inexpensive genomic analysis of evolving viral species for pandemic preparedness, to understand the evolution of circulating viral species, and for vaccine strain selection. We have developed one such approach based on previously described broad-range reverse transcription PCR/electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology. METHODS AND PRINCIPAL FINDINGS: Analysis of base compositions of RT-PCR amplicons from influenza core gene segments (PB1, PB2, PA, M, NS, NP) are used to provide sub-species identification and infer influenza virus H and N subtypes. Using this approach, we detected and correctly identified 92 mammalian and avian influenza isolates, representing 30 different H and N types, including 29 avian H5N1 isolates. Further, direct analysis of 656 human clinical respiratory specimens collected over a seven-year period (1999–2006) showed correct identification of the viral species and subtypes with >97% sensitivity and specificity. Base composition derived clusters inferred from this analysis showed 100% concordance to previously established clades. Ongoing surveillance of samples from the recent influenza virus seasons (2005–2006) showed evidence for emergence and establishment of new genotypes of circulating H3N2 strains worldwide. Mixed viral quasispecies were found in approximately 1% of these recent samples providing a view into viral evolution. CONCLUSION/SIGNIFICANCE: Thus, rapid RT-PCR/ESI-MS analysis can be used to simultaneously identify all species of influenza viruses with clade-level resolution, identify mixed viral populations and monitor global spread and emergence of novel viral genotypes. This high-throughput method promises to become an integral component of influenza surveillance.",2007 May 30,"['Sampath, Rangarajan', 'Russell, Kevin L.', 'Massire, Christian', 'Eshoo, Mark W.', 'Harpin, Vanessa', 'Blyn, Lawrence B.', 'Melton, Rachael', 'Ivy, Cristina', 'Pennella, Thuy', 'Li, Feng', 'Levene, Harold', 'Hall, Thomas A.', 'Libby, Brian', 'Fan, Nancy', 'Walcott, Demetrius J.', 'Ranken, Raymond', 'Pear, Michael', 'Schink, Amy', 'Gutierrez, Jose', 'Drader, Jared', 'Moore, David', 'Metzgar, David', 'Addington, Lynda', 'Rothman, Richard', 'Gaydos, Charlotte A.', 'Yang, Samuel', 'St. George, Kirsten', 'Fuschino, Meghan E.', 'Dean, Amy B.', 'Stallknecht, David E.', 'Goekjian, Ginger', 'Yingst, Samuel', 'Monteville, Marshall', 'Saad, Magdi D.', 'Whitehouse, Chris A.', 'Baldwin, Carson', 'Rudnick, Karl H.', 'Hofstadler, Steven A.', 'Lemon, Stanley M.', 'Ecker, David J.']",PLoS One,,,False
67f0d4bc3ea5b8ae8ae677ecde74ab21c7ad740b,PMC,Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry,http://dx.doi.org/10.1371/journal.pone.0000489,PMC1876795,17534439,CC0,"BACKGROUND: Effective influenza surveillance requires new methods capable of rapid and inexpensive genomic analysis of evolving viral species for pandemic preparedness, to understand the evolution of circulating viral species, and for vaccine strain selection. We have developed one such approach based on previously described broad-range reverse transcription PCR/electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology. METHODS AND PRINCIPAL FINDINGS: Analysis of base compositions of RT-PCR amplicons from influenza core gene segments (PB1, PB2, PA, M, NS, NP) are used to provide sub-species identification and infer influenza virus H and N subtypes. Using this approach, we detected and correctly identified 92 mammalian and avian influenza isolates, representing 30 different H and N types, including 29 avian H5N1 isolates. Further, direct analysis of 656 human clinical respiratory specimens collected over a seven-year period (1999–2006) showed correct identification of the viral species and subtypes with >97% sensitivity and specificity. Base composition derived clusters inferred from this analysis showed 100% concordance to previously established clades. Ongoing surveillance of samples from the recent influenza virus seasons (2005–2006) showed evidence for emergence and establishment of new genotypes of circulating H3N2 strains worldwide. Mixed viral quasispecies were found in approximately 1% of these recent samples providing a view into viral evolution. CONCLUSION/SIGNIFICANCE: Thus, rapid RT-PCR/ESI-MS analysis can be used to simultaneously identify all species of influenza viruses with clade-level resolution, identify mixed viral populations and monitor global spread and emergence of novel viral genotypes. This high-throughput method promises to become an integral component of influenza surveillance.",2007 May 30,"['Sampath, Rangarajan', 'Russell, Kevin L.', 'Massire, Christian', 'Eshoo, Mark W.', 'Harpin, Vanessa', 'Blyn, Lawrence B.', 'Melton, Rachael', 'Ivy, Cristina', 'Pennella, Thuy', 'Li, Feng', 'Levene, Harold', 'Hall, Thomas A.', 'Libby, Brian', 'Fan, Nancy', 'Walcott, Demetrius J.', 'Ranken, Raymond', 'Pear, Michael', 'Schink, Amy', 'Gutierrez, Jose', 'Drader, Jared', 'Moore, David', 'Metzgar, David', 'Addington, Lynda', 'Rothman, Richard', 'Gaydos, Charlotte A.', 'Yang, Samuel', 'St. George, Kirsten', 'Fuschino, Meghan E.', 'Dean, Amy B.', 'Stallknecht, David E.', 'Goekjian, Ginger', 'Yingst, Samuel', 'Monteville, Marshall', 'Saad, Magdi D.', 'Whitehouse, Chris A.', 'Baldwin, Carson', 'Rudnick, Karl H.', 'Hofstadler, Steven A.', 'Lemon, Stanley M.', 'Ecker, David J.']",PLoS One,,,False
93549e874bd97796034c7f22ad3095af3b8d8d7e,PMC,Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry,http://dx.doi.org/10.1371/journal.pone.0000489,PMC1876795,17534439,CC0,"BACKGROUND: Effective influenza surveillance requires new methods capable of rapid and inexpensive genomic analysis of evolving viral species for pandemic preparedness, to understand the evolution of circulating viral species, and for vaccine strain selection. We have developed one such approach based on previously described broad-range reverse transcription PCR/electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology. METHODS AND PRINCIPAL FINDINGS: Analysis of base compositions of RT-PCR amplicons from influenza core gene segments (PB1, PB2, PA, M, NS, NP) are used to provide sub-species identification and infer influenza virus H and N subtypes. Using this approach, we detected and correctly identified 92 mammalian and avian influenza isolates, representing 30 different H and N types, including 29 avian H5N1 isolates. Further, direct analysis of 656 human clinical respiratory specimens collected over a seven-year period (1999–2006) showed correct identification of the viral species and subtypes with >97% sensitivity and specificity. Base composition derived clusters inferred from this analysis showed 100% concordance to previously established clades. Ongoing surveillance of samples from the recent influenza virus seasons (2005–2006) showed evidence for emergence and establishment of new genotypes of circulating H3N2 strains worldwide. Mixed viral quasispecies were found in approximately 1% of these recent samples providing a view into viral evolution. CONCLUSION/SIGNIFICANCE: Thus, rapid RT-PCR/ESI-MS analysis can be used to simultaneously identify all species of influenza viruses with clade-level resolution, identify mixed viral populations and monitor global spread and emergence of novel viral genotypes. This high-throughput method promises to become an integral component of influenza surveillance.",2007 May 30,"['Sampath, Rangarajan', 'Russell, Kevin L.', 'Massire, Christian', 'Eshoo, Mark W.', 'Harpin, Vanessa', 'Blyn, Lawrence B.', 'Melton, Rachael', 'Ivy, Cristina', 'Pennella, Thuy', 'Li, Feng', 'Levene, Harold', 'Hall, Thomas A.', 'Libby, Brian', 'Fan, Nancy', 'Walcott, Demetrius J.', 'Ranken, Raymond', 'Pear, Michael', 'Schink, Amy', 'Gutierrez, Jose', 'Drader, Jared', 'Moore, David', 'Metzgar, David', 'Addington, Lynda', 'Rothman, Richard', 'Gaydos, Charlotte A.', 'Yang, Samuel', 'St. George, Kirsten', 'Fuschino, Meghan E.', 'Dean, Amy B.', 'Stallknecht, David E.', 'Goekjian, Ginger', 'Yingst, Samuel', 'Monteville, Marshall', 'Saad, Magdi D.', 'Whitehouse, Chris A.', 'Baldwin, Carson', 'Rudnick, Karl H.', 'Hofstadler, Steven A.', 'Lemon, Stanley M.', 'Ecker, David J.']",PLoS One,,,False
c65f0939cf35a0f04bf93bd6e8f771b8521563a5,PMC,Transmission Parameters of the 2001 Foot and Mouth Epidemic in Great Britain,http://dx.doi.org/10.1371/journal.pone.0000502,PMC1876810,17551582,CC BY,"Despite intensive ongoing research, key aspects of the spatial-temporal evolution of the 2001 foot and mouth disease (FMD) epidemic in Great Britain (GB) remain unexplained. Here we develop a Markov Chain Monte Carlo (MCMC) method for estimating epidemiological parameters of the 2001 outbreak for a range of simple transmission models. We make the simplifying assumption that infectious farms were completely observed in 2001, equivalent to assuming that farms that were proactively culled but not diagnosed with FMD were not infectious, even if some were infected. We estimate how transmission parameters varied through time, highlighting the impact of the control measures on the progression of the epidemic. We demonstrate statistically significant evidence for assortative contact patterns between animals of the same species. Predictive risk maps of the transmission potential in different geographic areas of GB are presented for the fitted models.",2007 Jun 6,"['Chis Ster, Irina', 'Ferguson, Neil M.']",PLoS One,,,True
8275311de465e4fdbb25ebddf76302cd4603c36c,PMC,Transparent Development of the WHO Rapid Advice Guidelines,http://dx.doi.org/10.1371/journal.pmed.0040119,PMC1877972,17535099,CC0,"Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.",2007 May 29,"['Schünemann, Holger J', 'Hill, Suzanne R', 'Kakad, Meetali', 'Vist, Gunn E', 'Bellamy, Richard', 'Stockman, Lauren', 'Wisløff, Torbjørn Fosen', 'Mar, Chris Del', 'Hayden, Frederick', 'Uyeki, Timothy M', 'Farrar, Jeremy', 'Yazdanpanah, Yazdan', 'Zucker, Howard', 'Beigel, John', 'Chotpitayasunondh, Tawee', 'Hien, Tran Tinh', 'Özbay, Bülent', 'Sugaya, Norio', 'Oxman, Andrew D']",PLoS Med,,,True
849b571a103b4c39b2515f3769da04a6ff4918ae,PMC,Transparent Development of the WHO Rapid Advice Guidelines,http://dx.doi.org/10.1371/journal.pmed.0040119,PMC1877972,17535099,CC0,"Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.",2007 May 29,"['Schünemann, Holger J', 'Hill, Suzanne R', 'Kakad, Meetali', 'Vist, Gunn E', 'Bellamy, Richard', 'Stockman, Lauren', 'Wisløff, Torbjørn Fosen', 'Mar, Chris Del', 'Hayden, Frederick', 'Uyeki, Timothy M', 'Farrar, Jeremy', 'Yazdanpanah, Yazdan', 'Zucker, Howard', 'Beigel, John', 'Chotpitayasunondh, Tawee', 'Hien, Tran Tinh', 'Özbay, Bülent', 'Sugaya, Norio', 'Oxman, Andrew D']",PLoS Med,,,False
06c06c96cc93d025b70468793358918fa3c96978,PMC,Transparent Development of the WHO Rapid Advice Guidelines,http://dx.doi.org/10.1371/journal.pmed.0040119,PMC1877972,17535099,CC0,"Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.",2007 May 29,"['Schünemann, Holger J', 'Hill, Suzanne R', 'Kakad, Meetali', 'Vist, Gunn E', 'Bellamy, Richard', 'Stockman, Lauren', 'Wisløff, Torbjørn Fosen', 'Mar, Chris Del', 'Hayden, Frederick', 'Uyeki, Timothy M', 'Farrar, Jeremy', 'Yazdanpanah, Yazdan', 'Zucker, Howard', 'Beigel, John', 'Chotpitayasunondh, Tawee', 'Hien, Tran Tinh', 'Özbay, Bülent', 'Sugaya, Norio', 'Oxman, Andrew D']",PLoS Med,,,False
492da4648300bbc57c649c5558016893b1fa47d7,PMC,Transparent Development of the WHO Rapid Advice Guidelines,http://dx.doi.org/10.1371/journal.pmed.0040119,PMC1877972,17535099,CC0,"Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.",2007 May 29,"['Schünemann, Holger J', 'Hill, Suzanne R', 'Kakad, Meetali', 'Vist, Gunn E', 'Bellamy, Richard', 'Stockman, Lauren', 'Wisløff, Torbjørn Fosen', 'Mar, Chris Del', 'Hayden, Frederick', 'Uyeki, Timothy M', 'Farrar, Jeremy', 'Yazdanpanah, Yazdan', 'Zucker, Howard', 'Beigel, John', 'Chotpitayasunondh, Tawee', 'Hien, Tran Tinh', 'Özbay, Bülent', 'Sugaya, Norio', 'Oxman, Andrew D']",PLoS Med,,,False
dbe2626b505d8655d0062401ea8b901140fb1ca4,PMC,Transparent Development of the WHO Rapid Advice Guidelines,http://dx.doi.org/10.1371/journal.pmed.0040119,PMC1877972,17535099,CC0,"Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.",2007 May 29,"['Schünemann, Holger J', 'Hill, Suzanne R', 'Kakad, Meetali', 'Vist, Gunn E', 'Bellamy, Richard', 'Stockman, Lauren', 'Wisløff, Torbjørn Fosen', 'Mar, Chris Del', 'Hayden, Frederick', 'Uyeki, Timothy M', 'Farrar, Jeremy', 'Yazdanpanah, Yazdan', 'Zucker, Howard', 'Beigel, John', 'Chotpitayasunondh, Tawee', 'Hien, Tran Tinh', 'Özbay, Bülent', 'Sugaya, Norio', 'Oxman, Andrew D']",PLoS Med,,,False
bcfb37580928c801c7876dce689440d19707e18d,PMC,Transparent Development of the WHO Rapid Advice Guidelines,http://dx.doi.org/10.1371/journal.pmed.0040119,PMC1877972,17535099,CC0,"Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.",2007 May 29,"['Schünemann, Holger J', 'Hill, Suzanne R', 'Kakad, Meetali', 'Vist, Gunn E', 'Bellamy, Richard', 'Stockman, Lauren', 'Wisløff, Torbjørn Fosen', 'Mar, Chris Del', 'Hayden, Frederick', 'Uyeki, Timothy M', 'Farrar, Jeremy', 'Yazdanpanah, Yazdan', 'Zucker, Howard', 'Beigel, John', 'Chotpitayasunondh, Tawee', 'Hien, Tran Tinh', 'Özbay, Bülent', 'Sugaya, Norio', 'Oxman, Andrew D']",PLoS Med,,,False
79695b2d02cc1106f7cbf9ab80e3a53cee4b054e,PMC,Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses,http://dx.doi.org/10.1186/1743-422X-4-39,PMC1878474,17477867,CC BY,"Chloroquine is a 4-aminoquinoline previously used in malaria therapy and now becoming an emerging investigational antiviral drug due to its broad spectrum of antiviral activities. To explore whether the low pH-dependency of influenza A viruses might affect the antiviral effects of chloroquine at clinically achievable concentrations, we tested the antiviral effects of this drug on selected human and avian viruses belonging to different subtypes and displaying different pH requirements. Results showed a correlation between the responses to chloroquine and NH(4)Cl, a lysosomotropic agent known to increase the pH of intracellular vesicles. Time-of-addition experiments showed that the inhibitory effect of chloroquine was maximal when the drug had been added at the time of infection and was lost after 2 h post-infection. This timing approximately corresponds to that of virus/cell fusion. Moreover, there was a clear correlation between the EC(50 )of chloroquine in vitro and the electrostatic potential of the HA subunit (HA2) mediating the virus/cell fusion process. Overall, the present study highlights the critical importance of a host cell factor such as intravesicular pH in determining the anti-influenza activity of chloroquine and other lysosomotropic agents.",2007 May 3,"['Di Trani, Livia', 'Savarino, Andrea', 'Campitelli, Laura', 'Norelli, Sandro', 'Puzelli, Simona', ""D'Ostilio, Daniela"", 'Vignolo, Edoardo', 'Donatelli, Isabella', 'Cassone, Antonio']",Virol J,,,True
e5ec3d4854fa2bfba10cae487ea5271ed00a24fa,PMC,IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-γ production,http://dx.doi.org/10.1186/1471-2334-7-33,PMC1878480,17456233,CC BY,"BACKGROUND: Interferon-gamma is a key cytokine in the protective responses against intracellular pathogens. A single nucleotide polymorphism (SNP) located in the first intron of the human IFN-γ gene can putatively influence the secretion of cytokine with an impact on infection outcome as demonstrated for tuberculosis and other complex diseases. Our aim was to investigate the putative association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL) and also the influence of this SNP in the secretion of IFN-γ in vitro. METHODS: Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML) and 609 healthy volunteers were evaluated. The genotype of +874 region in the IFN-γ gene was carried out by Amplification Refractory Mutational System (ARMS-PCR). Leishmania-induced IFN-γ production on peripheral blood mononuclear cell (PBMC) culture supernatants was assessed by ELISA. RESULTS: There are no differences between +874T/A SNP frequency in cases and controls or in ML versus CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower levels of IFN-γ than TA/TT genotypes. In mucosal cases, high and low IFN-γ producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers. CONCLUSION: Our results suggest that +874T/A polymorphism was not associated with either susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could be involved in the pathogenesis of leishmaniasis by influencing the amount of cytokine released by CL patients, although it could not prevent disease development. On the other hand, it is possible that in ML cases, other potential polymorphic regulatory genes such as TNF-α and IL-10 are also involved thus interfering with IFN-γ secretion.",2007 Apr 24,"['Matos, Guilherme Inocêncio', 'Covas, Claudia de J Fernandes', 'Bittar, Rita de Cássia', 'Gomes-Silva, Adriano', 'Marques, Fabiana', 'Maniero, Viviane C', 'Amato, Valdir S', 'Oliveira-Neto, Manoel P', 'Mattos, Marise da Silva', 'Pirmez, Claude', 'Sampaio, Elizabeth P', 'Moraes, Milton O', 'Da-Cruz, Alda Maria']",BMC Infect Dis,,,True
49b957bb681c7cae440ef4241a9fc99f37028d78,PMC,Prophylactic and Therapeutic Efficacy of Human Monoclonal Antibodies against H5N1 Influenza,http://dx.doi.org/10.1371/journal.pmed.0040178,PMC1880850,17535101,CC0,"BACKGROUND: New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI) H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs) and tested their efficacy for prophylaxis and therapy in a murine model of infection. METHODS AND FINDINGS: Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses. Supernatants from B cell lines were screened in a virus neutralization assay. B cell lines secreting neutralizing antibodies were cloned and the mAbs purified. The cross-reactivity of these antibodies for different strains of H5N1 was tested in vitro by neutralization assays, and their prophylactic and therapeutic efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19 neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140 neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1) in a dose-dependent manner. mAb prophylaxis provided a statistically significant reduction in pulmonary virus titer, reduced associated inflammation in the lungs, and restricted extrapulmonary dissemination of the virus. Therapeutic doses of FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1). mAbs FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1). CONCLUSIONS: These studies provide proof of concept that fully human mAbs with neutralizing activity can be rapidly generated from the peripheral blood of convalescent patients and that these mAbs are effective for the prevention and treatment of H5N1 infection in a mouse model. A panel of neutralizing, cross-reactive mAbs might be useful for prophylaxis or adjunctive treatment of human cases of H5N1 influenza.",2007 May 29,"['Simmons, Cameron P', 'Bernasconi, Nadia L', 'Suguitan, Amorsolo L', 'Mills, Kimberly', 'Ward, Jerrold M', 'Chau, Nguyen Van Vinh', 'Hien, Tran Tinh', 'Sallusto, Federica', 'Ha, Do Quang', 'Farrar, Jeremy', 'de Jong, Menno D', 'Lanzavecchia, Antonio', 'Subbarao, Kanta']",PLoS Med,,,True
2871cf7a741e9af5c94009d2cf5f368932f6f47e,PMC,How Is WHO Responding to Global Public Health Threats?,http://dx.doi.org/10.1371/journal.pmed.0040197,PMC1880862,17535110,CC BY,The editors discuss two recent WHO initiatives on preparing for and responding to global public health threats: the WHO Rapid Advice Guidelines Group and the new revision of the International Health Regulations.,2007 May 29,,PLoS Med,,,True
1ff2f23a621ca476cd59ade285f8b9198ca178fd,PMC,Arthritis suppression by NADPH activation operates through an interferon-β pathway,http://dx.doi.org/10.1186/1741-7007-5-19,PMC1884140,17490473,CC BY,"BACKGROUND: A polymorphism in the activating component of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, neutrophil cytosolic factor 1 (NCF1), has previously been identified as a regulator of arthritis severity in mice and rats. This discovery resulted in a search for NADPH oxidase-activating substances as a potential new approach to treat autoimmune disorders such as rheumatoid arthritis (RA). We have recently shown that compounds inducing NCF1-dependent oxidative burst, e.g. phytol, have a strong ameliorating effect on arthritis in rats. However, the underlying molecular mechanism is still not clearly understood. The aim of this study was to use gene-expression profiling to understand the protective effect against arthritis of activation of NADPH oxidase in the immune system. RESULTS: Subcutaneous administration of phytol leads to an accumulation of the compound in the inguinal lymph nodes, with peak levels being reached approximately 10 days after administration. Hence, global gene-expression profiling on inguinal lymph nodes was performed 10 days after the induction of pristane-induced arthritis (PIA) and phytol administration. The differentially expressed genes could be divided into two pathways, consisting of genes regulated by different interferons. IFN-γ regulated the pathway associated with arthritis development, whereas IFN-β regulated the pathway associated with disease protection through phytol. Importantly, these two molecular pathways were also confirmed to differentiate between the arthritis-susceptible dark agouti (DA) rat, (with an Ncf-1(DA )allele that allows only low oxidative burst), and the arthritis-protected DA.Ncf-1(E3 )rat (with an Ncf1(E3 )allele that allows a stronger oxidative burst). CONCLUSION: Naturally occurring genetic polymorphisms in the Ncf-1 gene modulate the activity of the NADPH oxidase complex, which strongly regulates the severity of arthritis. We now show that the Ncf-1 allele that enhances oxidative burst and protects against arthritis is operating through an IFN-β-associated pathway, whereas the arthritis-driving allele operates through an IFN-γ-associated pathway. Treatment of arthritis-susceptible rats with an NADPH oxidase-activating substance, phytol, protects against arthritis. Interestingly, the treatment led to a restoration of the oxidative-burst effect and induction of a strikingly similar IFN-β-dependent pathway, as seen with the disease-protective Ncf1 polymorphism.",2007 May 9,"['Olofsson, Peter', 'Nerstedt, Annika', 'Hultqvist, Malin', 'Nilsson, Elisabeth C', 'Andersson, Sofia', 'Bergelin, Anna', 'Holmdahl, Rikard']",BMC Biol,,,True
6e2b123ad273e69afefb875594ac0fac7c785c74,PMC,Expression stability of commonly used reference genes in canine articular connective tissues,http://dx.doi.org/10.1186/1746-6148-3-7,PMC1884148,17484782,CC BY,"BACKGROUND: The quantification of gene expression in tissue samples requires the use of reference genes to normalise transcript numbers between different samples. Reference gene stability may vary between different tissues, and between the same tissue in different disease states. We evaluated the stability of 9 reference genes commonly used in human gene expression studies. Real-time reverse transcription PCR and a mathematical algorithm were used to establish which reference genes were most stably expressed in normal and diseased canine articular tissues and two canine cell lines stimulated with lipolysaccaride (LPS). RESULTS: The optimal reference genes for comparing gene expression data between normal and diseased infrapatella fat pad were RPL13A and YWHAZ (M = 0.56). The ideal reference genes for comparing normal and osteoarthritic (OA) cartilage were RPL13A and SDHA (M = 0.57). The best reference genes for comparing normal and ruptured canine cranial cruciate ligament were B2M and TBP (M = 0.59). The best reference genes for normalising gene expression data from normal and LPS stimulated cell lines were SDHA and YWHAZ (K6) or SDHA and HMBS (DH82), which had expression stability (M) values of 0.05 (K6) and 0.07 (DH82) respectively. The number of reference genes required to reduce pairwise variation (V) to <0.20 was 4 for cell lines, 5 for cartilage, 7 for cranial cruciate ligament and 8 for fat tissue. Reference gene stability was not related to the level of gene expression. CONCLUSION: The reference genes demonstrating the most stable expression within each different canine articular tissue were identified, but no single reference gene was identified as having stable expression in all different tissue types. This study underlines the necessity to select reference genes on the basis of tissue and disease specific expression profile evaluation and highlights the requirement for the identification of new reference genes with greater expression stability for use in canine articular tissue gene expression studies.",2007 May 7,"['Ayers, Duncan', 'Clements, Dylan N', 'Salway, Fiona', 'Day, Philip JR']",BMC Vet Res,,,True
37fe4be4d997e01fa069ab31bbe1a0090356500a,PMC,Early efforts in modeling the incubation period of infectious diseases with an acute course of illness,http://dx.doi.org/10.1186/1742-7622-4-2,PMC1884151,17466070,CC BY,"The incubation period of infectious diseases, the time from infection with a microorganism to onset of disease, is directly relevant to prevention and control. Since explicit models of the incubation period enhance our understanding of the spread of disease, previous classic studies were revisited, focusing on the modeling methods employed and paying particular attention to relatively unknown historical efforts. The earliest study on the incubation period of pandemic influenza was published in 1919, providing estimates of the incubation period of Spanish flu using the daily incidence on ships departing from several ports in Australia. Although the study explicitly dealt with an unknown time of exposure, the assumed periods of exposure, which had an equal probability of infection, were too long, and thus, likely resulted in slight underestimates of the incubation period. After the suggestion that the incubation period follows lognormal distribution, Japanese epidemiologists extended this assumption to estimates of the time of exposure during a point source outbreak. Although the reason why the incubation period of acute infectious diseases tends to reveal a right-skewed distribution has been explored several times, the validity of the lognormal assumption is yet to be fully clarified. At present, various different distributions are assumed, and the lack of validity in assuming lognormal distribution is particularly apparent in the case of slowly progressing diseases. The present paper indicates that (1) analysis using well-defined short periods of exposure with appropriate statistical methods is critical when the exact time of exposure is unknown, and (2) when assuming a specific distribution for the incubation period, comparisons using different distributions are needed in addition to estimations using different datasets, analyses of the determinants of incubation period, and an understanding of the underlying disease mechanisms.",2007 May 11,"Nishiura, Hiroshi",Emerg Themes Epidemiol,,,True
f34b80981d443f5ea437f156a047bfbd66a51090,PMC,Early efforts in modeling the incubation period of infectious diseases with an acute course of illness,http://dx.doi.org/10.1186/1742-7622-4-2,PMC1884151,17466070,CC BY,"The incubation period of infectious diseases, the time from infection with a microorganism to onset of disease, is directly relevant to prevention and control. Since explicit models of the incubation period enhance our understanding of the spread of disease, previous classic studies were revisited, focusing on the modeling methods employed and paying particular attention to relatively unknown historical efforts. The earliest study on the incubation period of pandemic influenza was published in 1919, providing estimates of the incubation period of Spanish flu using the daily incidence on ships departing from several ports in Australia. Although the study explicitly dealt with an unknown time of exposure, the assumed periods of exposure, which had an equal probability of infection, were too long, and thus, likely resulted in slight underestimates of the incubation period. After the suggestion that the incubation period follows lognormal distribution, Japanese epidemiologists extended this assumption to estimates of the time of exposure during a point source outbreak. Although the reason why the incubation period of acute infectious diseases tends to reveal a right-skewed distribution has been explored several times, the validity of the lognormal assumption is yet to be fully clarified. At present, various different distributions are assumed, and the lack of validity in assuming lognormal distribution is particularly apparent in the case of slowly progressing diseases. The present paper indicates that (1) analysis using well-defined short periods of exposure with appropriate statistical methods is critical when the exact time of exposure is unknown, and (2) when assuming a specific distribution for the incubation period, comparisons using different distributions are needed in addition to estimations using different datasets, analyses of the determinants of incubation period, and an understanding of the underlying disease mechanisms.",2007 May 11,"Nishiura, Hiroshi",Emerg Themes Epidemiol,,,False
98d0756af42f78bb74a9df2846729c36ba2f05ad,PMC,Early efforts in modeling the incubation period of infectious diseases with an acute course of illness,http://dx.doi.org/10.1186/1742-7622-4-2,PMC1884151,17466070,CC BY,"The incubation period of infectious diseases, the time from infection with a microorganism to onset of disease, is directly relevant to prevention and control. Since explicit models of the incubation period enhance our understanding of the spread of disease, previous classic studies were revisited, focusing on the modeling methods employed and paying particular attention to relatively unknown historical efforts. The earliest study on the incubation period of pandemic influenza was published in 1919, providing estimates of the incubation period of Spanish flu using the daily incidence on ships departing from several ports in Australia. Although the study explicitly dealt with an unknown time of exposure, the assumed periods of exposure, which had an equal probability of infection, were too long, and thus, likely resulted in slight underestimates of the incubation period. After the suggestion that the incubation period follows lognormal distribution, Japanese epidemiologists extended this assumption to estimates of the time of exposure during a point source outbreak. Although the reason why the incubation period of acute infectious diseases tends to reveal a right-skewed distribution has been explored several times, the validity of the lognormal assumption is yet to be fully clarified. At present, various different distributions are assumed, and the lack of validity in assuming lognormal distribution is particularly apparent in the case of slowly progressing diseases. The present paper indicates that (1) analysis using well-defined short periods of exposure with appropriate statistical methods is critical when the exact time of exposure is unknown, and (2) when assuming a specific distribution for the incubation period, comparisons using different distributions are needed in addition to estimations using different datasets, analyses of the determinants of incubation period, and an understanding of the underlying disease mechanisms.",2007 May 11,"Nishiura, Hiroshi",Emerg Themes Epidemiol,,,True
2616c5aef5cc1449e5a6b07264e1611efc93f4df,PMC,Accurate Reproduction of 161 Small-Molecule Complex Crystal Structures using the EUDOC Program: Expanding the Use of EUDOC to Supramolecular Chemistry,http://dx.doi.org/10.1371/journal.pone.0000531,PMC1888730,17565384,CC BY,"EUDOC is a docking program that has successfully predicted small-molecule-bound protein complexes and identified drug leads from chemical databases. To expand the application of the EUDOC program to supramolecular chemistry, we tested its ability to reproduce crystal structures of small-molecule complexes. Of 161 selected crystal structures of small-molecule guest-host complexes, EUDOC reproduced all these crystal structures with guest structure mass-weighted root mean square deviations (mwRMSDs) of <1.0 Å relative to the corresponding crystal structures. In addition, the average interaction energy of these 161 guest-host complexes (−50.1 kcal/mol) was found to be nearly half of that of 153 previously tested small-molecule-bound protein complexes (−108.5 kcal/mol), according to the interaction energies calculated by EUDOC. 31 of the 161 complexes could not be reproduced with mwRMSDs of <1.0 Å if neighboring hosts in the crystal structure of a guest-host complex were not included as part of the multimeric host system, whereas two of the 161 complexes could not be reproduced with mwRMSDs of <1.0 Å if water molecules were excluded from the host system. These results demonstrate the significant influence of crystal packing on small molecule complexation and suggest that EUDOC is able to predict small-molecule complexes and that it is useful for the design of new materials, molecular sensors, and multimeric inhibitors of protein-protein interactions.",2007 Jun 13,"['Wang, Qi', 'Pang, Yuan-Ping']",PLoS One,,,True
eb07f3436bd925c0de35ecbe26930536e8bcf200,PMC,"Time variations in the transmissibility of pandemic influenza in Prussia, Germany, from 1918–19",http://dx.doi.org/10.1186/1742-4682-4-20,PMC1892008,17547753,CC BY,"BACKGROUND: Time variations in transmission potential have rarely been examined with regard to pandemic influenza. This paper reanalyzes the temporal distribution of pandemic influenza in Prussia, Germany, from 1918–19 using the daily numbers of deaths, which totaled 8911 from 29 September 1918 to 1 February 1919, and the distribution of the time delay from onset to death in order to estimate the effective reproduction number, Rt, defined as the actual average number of secondary cases per primary case at a given time. RESULTS: A discrete-time branching process was applied to back-calculated incidence data, assuming three different serial intervals (i.e. 1, 3 and 5 days). The estimated reproduction numbers exhibited a clear association between the estimates and choice of serial interval; i.e. the longer the assumed serial interval, the higher the reproduction number. Moreover, the estimated reproduction numbers did not decline monotonically with time, indicating that the patterns of secondary transmission varied with time. These tendencies are consistent with the differences in estimates of the reproduction number of pandemic influenza in recent studies; high estimates probably originate from a long serial interval and a model assumption about transmission rate that takes no account of time variation and is applied to the entire epidemic curve. CONCLUSION: The present findings suggest that in order to offer robust assessments it is critically important to clarify in detail the natural history of a disease (e.g. including the serial interval) as well as heterogeneous patterns of transmission. In addition, given that human contact behavior probably influences transmissibility, individual countermeasures (e.g. household quarantine and mask-wearing) need to be explored to construct effective non-pharmaceutical interventions.",2007 Jun 4,"Nishiura, Hiroshi",Theor Biol Med Model,,,True
82946d26f79e85f1b37f6fd965dc1d8a2ceb0c4d,PMC,Cyclooxygenase activity is important for efficient replication of mouse hepatitis virus at an early stage of infection,http://dx.doi.org/10.1186/1743-422X-4-55,PMC1892777,17555580,CC BY,"Cyclooxygenases (COXs) play a significant role in many different viral infections with respect to replication and pathogenesis. Here we investigated the role of COXs in the mouse hepatitis coronavirus (MHV) infection cycle. Blocking COX activity by different inhibitors or by RNA interference affected MHV infection in different cells. The COX inhibitors reduced MHV infection at a post-binding step, but early in the replication cycle. Both viral RNA and viral protein synthesis were affected with subsequent loss of progeny virus production. Thus, COX activity appears to be required for efficient MHV replication, providing a potential target for anti-coronaviral therapy.",2007 Jun 7,"['Raaben, Matthijs', 'Einerhand, Alexandra WC', 'Taminiau, Lucas JA', 'van Houdt, Michel', 'Bouma, Janneke', 'Raatgeep, Rolien H', 'Büller, Hans A', 'de Haan, Cornelis AM', 'Rossen, John WA']",Virol J,,,True
418f1b85e589f3ac37ffc37075b6e558e510fa74,PMC,Designing and conducting tabletop exercises to assess public health preparedness for manmade and naturally occurring biological threats,http://dx.doi.org/10.1186/1471-2458-7-92,PMC1894789,17535426,CC BY,"BACKGROUND: Since 2001, state and local health departments in the United States (US) have accelerated efforts to prepare for high-impact public health emergencies. One component of these activities has been the development and conduct of exercise programs to assess capabilities, train staff and build relationships. This paper summarizes lessons learned from tabletop exercises about public health emergency preparedness and about the process of developing, conducting, and evaluating them. METHODS: We developed, conducted, and evaluated 31 tabletop exercises in partnership with state and local health departments throughout the US from 2003 to 2006. Participant self evaluations, after action reports, and tabletop exercise evaluation forms were used to identify aspects of the exercises themselves, as well as public health emergency responses that participants found more or less challenging, and to highlight lessons learned about tabletop exercise design. RESULTS: Designing the exercises involved substantial collaboration with representatives from participating health departments to assure that the scenarios were credible, focused attention on local preparedness needs and priorities, and were logistically feasible to implement. During execution of the exercises, nearly all health departments struggled with a common set of challenges relating to disease surveillance, epidemiologic investigations, communications, command and control, and health care surge capacity. In contrast, performance strengths were more varied across participating sites, reflecting specific attributes of individual health departments or communities, experience with actual public health emergencies, or the emphasis of prior preparedness efforts. CONCLUSION: The design, conduct, and evaluation of the tabletop exercises described in this report benefited from collaborative planning that involved stakeholders from participating health departments and exercise developers and facilitators from outside the participating agencies. While these exercises identified both strengths and vulnerabilities in emergency preparedness, additional work is needed to develop reliable metrics to gauge exercise performance, inform follow-up action steps, and to develop re-evaluation exercise designs that assess the impact of post-exercise interventions.",2007 May 29,"['Dausey, David J', 'Buehler, James W', 'Lurie, Nicole']",BMC Public Health,,,True
d508ee56bf2773ed13b19b85295c8e8709781bb7,PMC,Population mortality during the outbreak of Severe Acute Respiratory Syndrome in Toronto,http://dx.doi.org/10.1186/1471-2458-7-93,PMC1894965,17535440,CC BY,"BACKGROUND: Extraordinary infection control measures limited access to medical care in the Greater Toronto Area during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. The objective of this study was to determine if the period of these infection control measures was associated with changes in overall population mortality due to causes other than SARS. METHODS: Observational study of death registry data, using Poisson regression and interrupted time-series analysis to examine all-cause mortality rates (excluding deaths due to SARS) before, during, and after the SARS outbreak. The population of Ontario was grouped into the Greater Toronto Area (N = 2.9 million) and the rest of Ontario (N = 9.3 million) based upon the level of restrictions on delivery of clinical services during the SARS outbreak. RESULTS: There was no significant change in mortality in the Greater Toronto Area before, during, and after the period of the SARS outbreak in 2003 compared to the corresponding time periods in 2002 and 2001. The rate ratio for all-cause mortality during the SARS outbreak was 0.99 [95% Confidence Interval (CI) 0.93–1.06] compared to 2002 and 0.96 [95% CI 0.90–1.03] compared to 2001. An interrupted time series analysis found no significant change in mortality rates in the Greater Toronto Area associated with the period of the SARS outbreak. CONCLUSION: Limitations on access to medical services during the 2003 SARS outbreak in Toronto had no observable impact on short-term population mortality. Effects on morbidity and long-term mortality were not assessed. Efforts to contain future infectious disease outbreaks due to influenza or other agents must consider effects on access to essential health care services.",2007 May 29,"['Hwang, Stephen W', 'Cheung, Angela M', 'Moineddin, Rahim', 'Bell, Chaim M']",BMC Public Health,,,True
fe8ae98f3112f0ecf862177dd5745232b9d1f966,PMC,An Epidemiological Network Model for Disease Outbreak Detection,http://dx.doi.org/10.1371/journal.pmed.0040210,PMC1896205,17593895,CC BY,"BACKGROUND: Advanced disease-surveillance systems have been deployed worldwide to provide early detection of infectious disease outbreaks and bioterrorist attacks. New methods that improve the overall detection capabilities of these systems can have a broad practical impact. Furthermore, most current generation surveillance systems are vulnerable to dramatic and unpredictable shifts in the health-care data that they monitor. These shifts can occur during major public events, such as the Olympics, as a result of population surges and public closures. Shifts can also occur during epidemics and pandemics as a result of quarantines, the worried-well flooding emergency departments or, conversely, the public staying away from hospitals for fear of nosocomial infection. Most surveillance systems are not robust to such shifts in health-care utilization, either because they do not adjust baselines and alert-thresholds to new utilization levels, or because the utilization shifts themselves may trigger an alarm. As a result, public-health crises and major public events threaten to undermine health-surveillance systems at the very times they are needed most. METHODS AND FINDINGS: To address this challenge, we introduce a class of epidemiological network models that monitor the relationships among different health-care data streams instead of monitoring the data streams themselves. By extracting the extra information present in the relationships between the data streams, these models have the potential to improve the detection capabilities of a system. Furthermore, the models' relational nature has the potential to increase a system's robustness to unpredictable baseline shifts. We implemented these models and evaluated their effectiveness using historical emergency department data from five hospitals in a single metropolitan area, recorded over a period of 4.5 y by the Automated Epidemiological Geotemporal Integrated Surveillance real-time public health–surveillance system, developed by the Children's Hospital Informatics Program at the Harvard-MIT Division of Health Sciences and Technology on behalf of the Massachusetts Department of Public Health. We performed experiments with semi-synthetic outbreaks of different magnitudes and simulated baseline shifts of different types and magnitudes. The results show that the network models provide better detection of localized outbreaks, and greater robustness to unpredictable shifts than a reference time-series modeling approach. CONCLUSIONS: The integrated network models of epidemiological data streams and their interrelationships have the potential to improve current surveillance efforts, providing better localized outbreak detection under normal circumstances, as well as more robust performance in the face of shifts in health-care utilization during epidemics and major public events.",2007 Jun 26,"['Reis, Ben Y', 'Kohane, Isaac S', 'Mandl, Kenneth D']",PLoS Med,,,True
853fa72687a51e0a938d05ef0c6c6fde3fbc361f,PMC,The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese,http://dx.doi.org/10.1186/1471-2334-7-50,PMC1899505,17540042,CC BY,"BACKGROUND: Chemokines play important roles in inflammation and antiviral action. We examined whether polymorphisms of RANTES, IP-10 and Mig affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). METHODS: We tested the polymorphisms of RANTES, IP-10 and Mig for their associations with SARS in 495 Hong Kong Chinese SARS patients and 578 controls. Then we tried to confirm the results in 356 Beijing Chinese SARS patients and 367 controls. RESULTS: RANTES -28 G allele was associated with SARS susceptibility in Hong Kong Chinese (P < 0.0001, OR = 2.80, 95%CI:2.11–3.71). Individuals with RANTES -28 CG and GG genotypes had a 3.28-fold (95%CI:2.32–4.64) and 3.06-fold (95%CI:1.47–6.39) increased risk of developing SARS respectively (P < 0.0001). This -28 G allele conferred risk of death in a gene-dosage dependent manner (P = 0.014) with CG and GG individuals having a 2.12-fold (95% CI: 1.11–4.06) and 4.01-fold (95% CI: 1.30–12.4) increased risk. For the replication of RANTES data in Beijing Chinese, the -28 G allele was not associated with susceptibility to SARS. However, -28 CG (OR = 4.27, 95%CI:1.64–11.1) and GG (OR = 3.34, 95%CI:0.37–30.7) were associated with admission to intensive care units or death due to SARS (P = 0.011). CONCLUSION: RANTES -28 G allele plays a role in the pathogenesis of SARS.",2007 Jun 1,"['Ng, Man Wai', 'Zhou, Gangqiao', 'Chong, Wai Po', 'Lee, Loretta Wing Yan', 'Law, Helen Ka Wai', 'Zhang, Hongxing', 'Wong, Wilfred Hing Sang', 'Fok, Susanna Fung Shan', 'Zhai, Yun', 'Yung, Raymond WH', 'Chow, Eudora Y', 'Au, Ka Leung', 'Chan, Eric YT', 'Lim, Wilina', 'Peiris, JS Malik', 'He, Fuchu', 'Lau, Yu Lung']",BMC Infect Dis,,,True
8f7db32196a87deaa43589b325f60156efc5a63a,PMC,Transfusion-transmitted infections,http://dx.doi.org/10.1186/1479-5876-5-25,PMC1904179,17553144,CC BY,"Although the risk of transfusion-transmitted infections today is lower than ever, the supply of safe blood products remains subject to contamination with known and yet to be identified human pathogens. Only continuous improvement and implementation of donor selection, sensitive screening tests and effective inactivation procedures can ensure the elimination, or at least reduction, of the risk of acquiring transfusion transmitted infections. In addition, ongoing education and up-to-date information regarding infectious agents that are potentially transmitted via blood components is necessary to promote the reporting of adverse events, an important component of transfusion transmitted disease surveillance. Thus, the collaboration of all parties involved in transfusion medicine, including national haemovigilance systems, is crucial for protecting a secure blood product supply from known and emerging blood-borne pathogens.",2007 Jun 6,"['Bihl, Florian', 'Castelli, Damiano', 'Marincola, Francesco', 'Dodd, Roger Y', 'Brander, Christian']",J Transl Med,,,True
2bf62ecb50fd95973de0bf6c1285ac3475fc4cc8,PMC,Transcript-level annotation of Affymetrix probesets improves the interpretation of gene expression data,http://dx.doi.org/10.1186/1471-2105-8-194,PMC1913542,17559689,CC BY,"BACKGROUND: The wide use of Affymetrix microarray in broadened fields of biological research has made the probeset annotation an important issue. Standard Affymetrix probeset annotation is at gene level, i.e. a probeset is precisely linked to a gene, and probeset intensity is interpreted as gene expression. The increased knowledge that one gene may have multiple transcript variants clearly brings up the necessity of updating this gene-level annotation to a refined transcript-level. RESULTS: Through performing rigorous alignments of the Affymetrix probe sequences against a comprehensive pool of currently available transcript sequences, and further linking the probesets to the International Protein Index, we generated transcript-level or protein-level annotation tables for two popular Affymetrix expression arrays, Mouse Genome 430A 2.0 Array and Human Genome U133A Array. Application of our new annotations in re-examining existing expression data sets shows increased expression consistency among synonymous probesets and strengthened expression correlation between interacting proteins. CONCLUSION: By refining the standard Affymetrix annotation of microarray probesets from the gene level to the transcript level and protein level, one can achieve a more reliable interpretation of their experimental data, which may lead to discovery of more profound regulatory mechanism.",2007 Jun 11,"['Yu, Hui', 'Wang, Feng', 'Tu, Kang', 'Xie, Lu', 'Li, Yuan-Yuan', 'Li, Yi-Xue']",BMC Bioinformatics,,,True
2ddd50da1dd398931c5db3d1734948ef27b705bd,PMC,Automated real time constant-specificity surveillance for disease outbreaks,http://dx.doi.org/10.1186/1472-6947-7-15,PMC1919360,17567912,CC BY,"BACKGROUND: For real time surveillance, detection of abnormal disease patterns is based on a difference between patterns observed, and those predicted by models of historical data. The usefulness of outbreak detection strategies depends on their specificity; the false alarm rate affects the interpretation of alarms. RESULTS: We evaluate the specificity of five traditional models: autoregressive, Serfling, trimmed seasonal, wavelet-based, and generalized linear. We apply each to 12 years of emergency department visits for respiratory infection syndromes at a pediatric hospital, finding that the specificity of the five models was almost always a non-constant function of the day of the week, month, and year of the study (p < 0.05). We develop an outbreak detection method, called the expectation-variance model, based on generalized additive modeling to achieve a constant specificity by accounting for not only the expected number of visits, but also the variance of the number of visits. The expectation-variance model achieves constant specificity on all three time scales, as well as earlier detection and improved sensitivity compared to traditional methods in most circumstances. CONCLUSION: Modeling the variance of visit patterns enables real-time detection with known, constant specificity at all times. With constant specificity, public health practitioners can better interpret the alarms and better evaluate the cost-effectiveness of surveillance systems.",2007 Jun 13,"['Wieland, Shannon C', 'Brownstein, John S', 'Berger, Bonnie', 'Mandl, Kenneth D']",BMC Med Inform Decis Mak,,,True
8309dc172cf91ff580779bbc1394a9692b798a86,PMC,Screen for ISG15-crossreactive Deubiquitinases,http://dx.doi.org/10.1371/journal.pone.0000679,PMC1919423,17653289,CC BY,"BACKGROUND: The family of ubiquitin-like molecules (UbLs) comprises several members, each of which has sequence, structural, or functional similarity to ubiquitin. ISG15 is a homolog of ubiquitin in vertebrates and is strongly upregulated following induction by type I interferon. ISG15 can be covalently attached to proteins, analogous to ubiquitination and with actual support of ubiquitin conjugating factors. Specific proteases are able to reverse modification with ubiquitin or UbLs by hydrolyzing the covalent bond between their C-termini and substrate proteins. The tail regions of ubiquitin and ISG15 are identical and we therefore hypothesized that promiscuous deubiquitinating proteases (DUBs) might exist, capable of recognizing both ubiquitin and ISG15. RESULTS: We have cloned and expressed 22 human DUBs, representing the major clades of the USP protease family. Utilizing suicide inhibitors based on ubiquitin and ISG15, we have identified USP2, USP5 (IsoT1), USP13 (IsoT3), and USP14 as ISG15-reactive proteases, in addition to the bona fide ISG15-specific protease USP18 (UBP43). USP14 is a proteasome-associated DUB, and its ISG15 isopeptidase activity increases when complexed with the proteasome. CONCLUSIONS: By evolutionary standards, ISG15 is a newcomer among the UbLs and it apparently not only utilizes the conjugating but also the deconjugating machinery of its more established relative ubiquitin. Functional overlap between these two posttranslational modifiers might therefore be more extensive than previously appreciated and explain the rather innocuous phenotype of ISG15 null mice.",2007 Jul 25,"['Catic, André', 'Fiebiger, Edda', 'Korbel, Gregory A.', 'Blom, Daniël', 'Galardy, Paul J.', 'Ploegh, Hidde L.']",PLoS One,,,True
4994fa72322bbf19120592304d92629226948d8e,PMC,Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif,http://dx.doi.org/10.1371/journal.pone.0000645,PMC1920550,17653272,CC BY,"To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. The corresponding synthetic peptides are expected to mimic structurally “native” epitopes. Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence. Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice. These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth. Circular dichroism studies indicated that the selected peptides assumed partial or high α-helical content. Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates. This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens.",2007 Jul 25,"['Villard, Viviane', 'Agak, George W.', 'Frank, Géraldine', 'Jafarshad, Ali', 'Servis, Catherine', 'Nébié, Issa', 'Sirima, Sodiomon B.', 'Felger, Ingrid', 'Arevalo-Herrera, Myriam', 'Herrera, Socrates', 'Heitz, Frederic', 'Bäcker, Volker', 'Druilhe, Pierre', 'Kajava, Andrey V.', 'Corradin, Giampietro']",PLoS One,,,True
deeacb8558e3403c69cd8db9f4e8e5214fd85c46,PMC,Identification and characterisation of the angiotensin converting enzyme-3 (ACE3) gene: a novel mammalian homologue of ACE,http://dx.doi.org/10.1186/1471-2164-8-194,PMC1925091,17597519,CC BY,"BACKGROUND: Mammalian angiotensin converting enzyme (ACE) plays a key role in blood pressure regulation. Although multiple ACE-like proteins exist in non-mammalian organisms, to date only one other ACE homologue, ACE2, has been identified in mammals. RESULTS: Here we report the identification and characterisation of the gene encoding a third homologue of ACE, termed ACE3, in several mammalian genomes. The ACE3 gene is located on the same chromosome downstream of the ACE gene. Multiple sequence alignment and molecular modelling have been employed to characterise the predicted ACE3 protein. In mouse, rat, cow and dog, the predicted protein has mutations in some of the critical residues involved in catalysis, including the catalytic Glu in the HEXXH zinc binding motif which is Gln, and ESTs or reverse-transcription PCR indicate that the gene is expressed. In humans, the predicted ACE3 protein has an intact HEXXH motif, but there are other deletions and insertions in the gene and no ESTs have been identified. CONCLUSION: In the genomes of several mammalian species there is a gene that encodes a novel, single domain ACE-like protein, ACE3. In mouse, rat, cow and dog ACE3, the catalytic Glu is replaced by Gln in the putative zinc binding motif, indicating that in these species ACE3 would lack catalytic activity as a zinc metalloprotease. In humans, no evidence was found that the ACE3 gene is expressed and the presence of deletions and insertions in the sequence indicate that ACE3 is a pseudogene.",2007 Jun 27,"['Rella, Monika', 'Elliot, Joann L', 'Revett, Timothy J', 'Lanfear, Jerry', 'Phelan, Anne', 'Jackson, Richard M', 'Turner, Anthony J', 'Hooper, Nigel M']",BMC Genomics,,,True
40e94ea7aba6cfaed881217032da16d4a5c2fd1d,PMC,Optimization and clinical validation of a pathogen detection microarray,http://dx.doi.org/10.1186/gb-2007-8-5-r93,PMC1929155,17531104,CC BY,"DNA microarrays used as 'genomic sensors' have great potential in clinical diagnostics. Biases inherent in random PCR-amplification, cross-hybridization effects, and inadequate microarray analysis, however, limit detection sensitivity and specificity. Here, we have studied the relationships between viral amplification efficiency, hybridization signal, and target-probe annealing specificity using a customized microarray platform. Novel features of this platform include the development of a robust algorithm that accurately predicts PCR bias during DNA amplification and can be used to improve PCR primer design, as well as a powerful statistical concept for inferring pathogen identity from probe recognition signatures. Compared to real-time PCR, the microarray platform identified pathogens with 94% accuracy (76% sensitivity and 100% specificity) in a panel of 36 patient specimens. Our findings show that microarrays can be used for the robust and accurate diagnosis of pathogens, and further substantiate the use of microarray technology in clinical diagnostics.",2007 May 28,"['Wong, Christopher W', 'Heng, Charlie Lee Wah', 'Wan Yee, Leong', 'Soh, Shirlena WL', 'Kartasasmita, Cissy B', 'Simoes, Eric AF', 'Hibberd, Martin L', 'Sung, Wing-Kin', 'Miller, Lance D']",Genome Biol,,,True
25a348f34236403317091db876b29fd5063528ed,PMC,Influenza pandemic preparedness: motivation for protection among small and medium businesses in Australia,http://dx.doi.org/10.1186/1471-2458-7-157,PMC1934907,17634112,CC BY,"BACKGROUND: Community-wide preparedness for pandemic influenza is an issue that has featured prominently in the recent news media, and is currently a priority for health authorities in many countries. The small and medium business sector is a major provider of private sector employment in Australia, yet we have little information about the preparedness of this sector for pandemic influenza. This study aimed to investigate the association between individual perceptions and preparedness for pandemic influenza among small and medium business owners and managers. METHODS: Semi-structured face-to-face interviews were conducted with 201 small and medium business owners or managers in New South Wales and Western Australia. Eligible small or medium businesses were defined as those that had less than 200 employees. Binomial logistic regression analysis was used to identify the predictors of having considered the impact of, having a plan for, and needing help to prepare for pandemic influenza. RESULTS: Approximately 6 per cent of participants reported that their business had a plan for pandemic influenza, 39 per cent reported that they had not thought at all about the impact of pandemic influenza on their business, and over 60 per cent stated that they required help to prepare for a pandemic. Beliefs about the severity of pandemic influenza and the ability to respond were significant independent predictors of having a plan for pandemic influenza, and the perception of the risk of pandemic influenza was the most important predictor of both having considered the impact of, and needing help to prepare for a pandemic. CONCLUSION: Our findings suggest that small and medium businesses in Australia are not currently well prepared for pandemic influenza. We found that beliefs about the risk, severity, and the ability to respond effectively to the threat of pandemic influenza are important predictors of preparedness. Campaigns targeting small and medium businesses should emphasise the severity of the consequences to their businesses if a pandemic were to occur, and, at the same time, reassure them that there are effective strategies capable of being implemented by small and medium businesses to deal with a pandemic.",2007 Jul 17,"['Watkins, Rochelle E', 'Cooke, Feonagh C', 'Donovan, Robert J', 'MacIntyre, C Raina', 'Itzwerth, Ralf', 'Plant, Aileen J']",BMC Public Health,,,True
555bbbbd23da02c97c6a4238937e31b5781438a9,PMC,Influenza pandemic intervention planning using InfluSim: pharmaceutical and non- pharmaceutical interventions,http://dx.doi.org/10.1186/1471-2334-7-76,PMC1939851,17629919,CC BY,"BACKGROUND: Influenza pandemic preparedness plans are currently developed and refined on national and international levels. Much attention has been given to the administration of antiviral drugs, but contact reduction can also be an effective part of mitigation strategies and has the advantage to be not limited per se. The effectiveness of these interventions depends on various factors which must be explored by sensitivity analyses, based on mathematical models. METHODS: We use the freely available planning tool InfluSim to investigate how pharmaceutical and non-pharmaceutical interventions can mitigate an influenza pandemic. In particular, we examine how intervention schedules, restricted stockpiles and contact reduction (social distancing measures and isolation of cases) determine the course of a pandemic wave and the success of interventions. RESULTS: A timely application of antiviral drugs combined with a quick implementation of contact reduction measures is required to substantially protract the peak of the epidemic and reduce its height. Delays in the initiation of antiviral treatment (e.g. because of parsimonious use of a limited stockpile) result in much more pessimistic outcomes and can even lead to the paradoxical effect that the stockpile is depleted earlier compared to early distribution of antiviral drugs. CONCLUSION: Pharmaceutical and non-pharmaceutical measures should not be used exclusively. The protraction of the pandemic wave is essential to win time while waiting for vaccine development and production. However, it is the height of the peak of an epidemic which can easily overtax general practitioners, hospitals or even whole public health systems, causing bottlenecks in basic and emergency medical care.",2007 Jul 13,"['Duerr, Hans P', 'Brockmann, Stefan O', 'Piechotowski, Isolde', 'Schwehm, Markus', 'Eichner, Martin']",BMC Infect Dis,,,True
a5701c6fbac36d0fcac9dc32cd78288f3f27f24b,PMC,Factor structure of the General Health Questionnaire (GHQ-12) in subjects who had suffered from the 2004 Niigata-Chuetsu Earthquake in Japan: a community-based study,http://dx.doi.org/10.1186/1471-2458-7-175,PMC1939990,17650342,CC BY,"BACKGROUND: Factor structure of the 12-item General Health Questionnaire (GHQ-12) was studied by a survey of subjects who had experienced the 2004 Niigata-Chuetsu earthquake (6.8 on the Richter scale) in Japan. METHODS: Psychological distress was measured at two years after the earthquake by using GHQ-12 in 2,107 subjects (99.0% response rate) who suffered the earthquake. GHQ-12 was scored by binary, chronic and Likert scoring method. Confirmatory factor analysis was used to reveal the factor structure of GHQ-12. Categorical regression analysis was performed to evaluate the relationships between various background factors and GHQ-12 scores. RESULTS: Confirmatory factor analysis revealed that the model consisting of the two factors and using chronic method gave the best goodness-of-fit among the various models for factor structure. Recovery in the scale for the factor 'social dysfunction' was remarkably impaired compared with that of the factor 'dysphoria'. Categorical regression analysis revealed that various factors, including advanced age, were associated with psychological distress. Advanced age affected the impaired recovery of factor 'social dysfunction' score as well as total GHQ score. CONCLUSION: The two-factor structure of GHQ-12 was conserved between the survey at five month and that at two years after the earthquake. Impaired recovery in the ability to cope with daily problems in the subjects who had experienced the earthquake was remarkable even at two years after the earthquake.",2007 Jul 24,"['Toyabe, Shin-ichi', 'Shioiri, Toshiki', 'Kobayashi, Kuriko', 'Kuwabara, Hideki', 'Koizumi, Masataka', 'Endo, Taro', 'Ito, Miki', 'Honma, Hiroko', 'Fukushima, Noboru', 'Someya, Toshiyuki', 'Akazawa, Kouhei']",BMC Public Health,,,True
c99be1ffda777de5b7f9e0ed6c04fd70ce0bc3e1,PMC,Coronavirus Non-Structural Protein 1 Is a Major Pathogenicity Factor: Implications for the Rational Design of Coronavirus Vaccines,http://dx.doi.org/10.1371/journal.ppat.0030109,PMC1941747,17696607,CC BY,"Attenuated viral vaccines can be generated by targeting essential pathogenicity factors. We report here the rational design of an attenuated recombinant coronavirus vaccine based on a deletion in the coding sequence of the non-structural protein 1 (nsp1). In cell culture, nsp1 of mouse hepatitis virus (MHV), like its SARS-coronavirus homolog, strongly reduced cellular gene expression. The effect of nsp1 on MHV replication in vitro and in vivo was analyzed using a recombinant MHV encoding a deletion in the nsp1-coding sequence. The recombinant MHV nsp1 mutant grew normally in tissue culture, but was severely attenuated in vivo. Replication and spread of the nsp1 mutant virus was restored almost to wild-type levels in type I interferon (IFN) receptor-deficient mice, indicating that nsp1 interferes efficiently with the type I IFN system. Importantly, replication of nsp1 mutant virus in professional antigen-presenting cells such as conventional dendritic cells and macrophages, and induction of type I IFN in plasmacytoid dendritic cells, was not impaired. Furthermore, even low doses of nsp1 mutant MHV elicited potent cytotoxic T cell responses and protected mice against homologous and heterologous virus challenge. Taken together, the presented attenuation strategy provides a paradigm for the development of highly efficient coronavirus vaccines.",2007 Aug 10,"['Züst, Roland', 'Cervantes-Barragán, Luisa', 'Kuri, Thomas', 'Blakqori, Gjon', 'Weber, Friedemann', 'Ludewig, Burkhard', 'Thiel, Volker']",PLoS Pathog,,,True
0e24e06b66ebf676c3d15bbcaf7120dc60413702,PMC,Functional Genomics Highlights Differential Induction of Antiviral Pathways in the Lungs of SARS-CoV–Infected Macaques,http://dx.doi.org/10.1371/journal.ppat.0030112,PMC1941749,17696609,CC BY,"The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis) that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL)-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.",2007 Aug 10,"['de Lang, Anna', 'Baas, Tracey', 'Teal, Thomas', 'Leijten, Lonneke M', 'Rain, Brandon', 'Osterhaus, Albert D', 'Haagmans, Bart L', 'Katze, Michael G']",PLoS Pathog,,,True
77a8c567572cf005f58dc577dc44f711aabe3fd4,PMC,Three-Dimensional Analysis of a Viral RNA Replication Complex Reveals a Virus-Induced Mini-Organelle,http://dx.doi.org/10.1371/journal.pbio.0050220,PMC1945040,17696647,CC BY,"Positive-strand RNA viruses are the largest genetic class of viruses and include many serious human pathogens. All positive-strand RNA viruses replicate their genomes in association with intracellular membrane rearrangements such as single- or double-membrane vesicles. However, the exact sites of RNA synthesis and crucial topological relationships between relevant membranes, vesicle interiors, surrounding lumens, and cytoplasm generally are poorly defined. We applied electron microscope tomography and complementary approaches to flock house virus (FHV)–infected Drosophila cells to provide the first 3-D analysis of such replication complexes. The sole FHV RNA replication factor, protein A, and FHV-specific 5-bromouridine 5'-triphosphate incorporation localized between inner and outer mitochondrial membranes inside ∼50-nm vesicles (spherules), which thus are FHV-induced compartments for viral RNA synthesis. All such FHV spherules were outer mitochondrial membrane invaginations with interiors connected to the cytoplasm by a necked channel of ∼10-nm diameter, which is sufficient for ribonucleotide import and product RNA export. Tomographic, biochemical, and other results imply that FHV spherules contain, on average, three RNA replication intermediates and an interior shell of ∼100 membrane-spanning, self-interacting protein As. The results identify spherules as the site of protein A and nascent RNA accumulation and define spherule topology, dimensions, and stoichiometry to reveal the nature and many details of the organization and function of the FHV RNA replication complex. The resulting insights appear relevant to many other positive-strand RNA viruses and support recently proposed structural and likely evolutionary parallels with retrovirus and double-stranded RNA virus virions.",2007 Sep 14,"['Kopek, Benjamin G', 'Perkins, Guy', 'Miller, David J', 'Ellisman, Mark H', 'Ahlquist, Paul']",PLoS Biol,,,True
b6eed04e43ad653c06247b10ab05d03bdccf04bc,PMC,Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic,http://dx.doi.org/10.1371/journal.pone.0000758,PMC1950082,17712406,CC BY,"Reproduction numbers, defined as averages of the number of people infected by a typical case, play a central role in tracking infectious disease outbreaks. The aim of this paper is to develop methods for estimating reproduction numbers which are simple enough that they could be applied with limited data or in real time during an outbreak. I present a new estimator for the individual reproduction number, which describes the state of the epidemic at a point in time rather than tracking individuals over time, and discuss some potential benefits. Then, to capture more of the detail that micro-simulations have shown is important in outbreak dynamics, I analyse a model of transmission within and between households, and develop a method to estimate the household reproduction number, defined as the number of households infected by each infected household. This method is validated by numerical simulations of the spread of influenza and measles using historical data, and estimates are obtained for would-be emerging epidemics of these viruses. I argue that the household reproduction number is useful in assessing the impact of measures that target the household for isolation, quarantine, vaccination or prophylactic treatment, and measures such as social distancing and school or workplace closures which limit between-household transmission, all of which play a key role in current thinking on future infectious disease mitigation.",2007 Aug 22,"Fraser, Christophe",PLoS One,,,True
aa244b14aba85cb4dc31dedbf92e9d6ac1dd25f3,PMC,Estimating Individual and Household Reproduction Numbers in an Emerging Epidemic,http://dx.doi.org/10.1371/journal.pone.0000758,PMC1950082,17712406,CC BY,"Reproduction numbers, defined as averages of the number of people infected by a typical case, play a central role in tracking infectious disease outbreaks. The aim of this paper is to develop methods for estimating reproduction numbers which are simple enough that they could be applied with limited data or in real time during an outbreak. I present a new estimator for the individual reproduction number, which describes the state of the epidemic at a point in time rather than tracking individuals over time, and discuss some potential benefits. Then, to capture more of the detail that micro-simulations have shown is important in outbreak dynamics, I analyse a model of transmission within and between households, and develop a method to estimate the household reproduction number, defined as the number of households infected by each infected household. This method is validated by numerical simulations of the spread of influenza and measles using historical data, and estimates are obtained for would-be emerging epidemics of these viruses. I argue that the household reproduction number is useful in assessing the impact of measures that target the household for isolation, quarantine, vaccination or prophylactic treatment, and measures such as social distancing and school or workplace closures which limit between-household transmission, all of which play a key role in current thinking on future infectious disease mitigation.",2007 Aug 22,"Fraser, Christophe",PLoS One,,,False
86febf1edc351777b6424be2ee9a2e521176dd98,PMC,Virus detection and identification using random multiplex (RT)-PCR with 3'-locked random primers,http://dx.doi.org/10.1186/1743-422X-4-65,PMC1950496,17598900,CC BY,"BACKGROUND: PCR-based detection and identification of viruses assumes a known, relatively stable genome. Unfortunately, high mutation rates may lead to extensive changes in viral nucleic acid sequences making dedicated PCR primer use problematic. Furthermore, in bioterrorism, viral consensus sequences can be genetically modified as a countermeasure to RT-PCR and DNA chip detection. Accordingly, there is a great need for the development of rapid and universal virus detection and identification technologies. RESULTS: We report herein that viral genomic DNA or RNA can be separated from host nucleic acids in plasma by filtration and nuclease digestion, and randomly amplified in a single PCR using a mixture of primers designed to be resistant to primer-dimer amplification (5'-VVVVVVVVAA-3', V = A, G or C; 3(8 )or 6561 primers). We have termed this novel PCR method Random Multiplex (RT)-PCR since hundreds of overlapping PCR amplifications occur simultaneously. Using this method, we have successfullydetected and partially sequenced 3 separate viruses in human plasma without using virus-specific reagents (i.e., Adenovirus Type 17, Coxsackievirus A7, and Respiratory Syncytial Virus B). The method is sensitive to ~1000 genome equivalents/ml and may represent the fastest means of detection of unknown viruses. CONCLUSION: These studies suggest that the further development of random multiplex (RT)-PCR may lead to a diagnostic assay that can universally detect viruses in donated blood products as well as in patients suffering with idiopathic disease states of possible viral etiology.",2007 Jun 28,"['Clem, Amy L', 'Sims, Jonathan', 'Telang, Sucheta', 'Eaton, John W', 'Chesney, Jason']",Virol J,,,True
fb3c146b1766b4aa33df1637742bf93159967289,PMC,Natural Killer Cells Promote Early CD8 T Cell Responses against Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.0030123,PMC1950948,17722980,CC BY,"Understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies. While natural killer (NK) cells can directly contribute to the control of viral replication, whether, and how, they may help orchestrate global antiviral defense is largely unknown. To address this question, we took advantage of the well-defined molecular interactions involved in the recognition of mouse cytomegalovirus (MCMV) by NK cells. By using congenic or mutant mice and wild-type versus genetically engineered viruses, we examined the consequences on antiviral CD8 T cell responses of specific defects in the ability of the NK cells to control MCMV. This system allowed us to demonstrate, to our knowledge for the first time, that NK cells accelerate CD8 T cell responses against a viral infection in vivo. Moreover, we identify the underlying mechanism as the ability of NK cells to limit IFN-α/β production to levels not immunosuppressive to the host. This is achieved through the early control of cytomegalovirus, which dramatically reduces the activation of plasmacytoid dendritic cells (pDCs) for cytokine production, preserves the conventional dendritic cell (cDC) compartment, and accelerates antiviral CD8 T cell responses. Conversely, exogenous IFN-α administration in resistant animals ablates cDCs and delays CD8 T cell activation in the face of NK cell control of viral replication. Collectively, our data demonstrate that the ability of NK cells to respond very early to cytomegalovirus infection critically contributes to balance the intensity of other innate immune responses, which dampens early immunopathology and promotes optimal initiation of antiviral CD8 T cell responses. Thus, the extent to which NK cell responses benefit the host goes beyond their direct antiviral effects and extends to the prevention of innate cytokine shock and to the promotion of adaptive immunity.",2007 Aug 24,"['Robbins, Scott H', 'Bessou, Gilles', 'Cornillon, Amélie', 'Zucchini, Nicolas', 'Rupp, Brigitte', 'Ruzsics, Zsolt', 'Sacher, Torsten', 'Tomasello, Elena', 'Vivier, Eric', 'Koszinowski, Ulrich H', 'Dalod, Marc']",PLoS Pathog,,,True
b0218dd5c965f2c92348a50f46ea2e271a56c7c8,PMC,Persistent Infection and Promiscuous Recombination of Multiple Genotypes of an RNA Virus within a Single Host Generate Extensive Diversity,http://dx.doi.org/10.1371/journal.pone.0000917,PMC1975466,17878952,CC BY,"Recombination and reassortment of viral genomes are major processes contributing to the creation of new, emerging viruses. These processes are especially significant in long-term persistent infections where multiple viral genotypes co-replicate in a single host, generating abundant genotypic variants, some of which may possess novel host-colonizing and pathogenicity traits. In some plants, successive vegetative propagation of infected tissues and introduction of new genotypes of a virus by vector transmission allows for viral populations to increase in complexity for hundreds of years allowing co-replication and subsequent recombination of the multiple viral genotypes. Using a resequencing microarray, we examined a persistent infection by a Citrus tristeza virus (CTV) complex in citrus, a vegetatively propagated, globally important fruit crop, and found that the complex comprised three major and a number of minor genotypes. Subsequent deep sequencing analysis of the viral population confirmed the presence of the three major CTV genotypes and, in addition, revealed that the minor genotypes consisted of an extraordinarily large number of genetic variants generated by promiscuous recombination between the major genotypes. Further analysis provided evidence that some of the recombinants underwent subsequent divergence, further increasing the genotypic complexity. These data demonstrate that persistent infection of multiple viral genotypes within a host organism is sufficient to drive the large-scale production of viral genetic variants that may evolve into new and emerging viruses.",2007 Sep 19,"['Weng, Ziming', 'Barthelson, Roger', 'Gowda, Siddarame', 'Hilf, Mark E.', 'Dawson, William O.', 'Galbraith, David W.', 'Xiong, Zhongguo']",PLoS One,,,True
c235de11eceb5f9f55e0b361818e959d4482b621,PMC,Persistent Infection and Promiscuous Recombination of Multiple Genotypes of an RNA Virus within a Single Host Generate Extensive Diversity,http://dx.doi.org/10.1371/journal.pone.0000917,PMC1975466,17878952,CC BY,"Recombination and reassortment of viral genomes are major processes contributing to the creation of new, emerging viruses. These processes are especially significant in long-term persistent infections where multiple viral genotypes co-replicate in a single host, generating abundant genotypic variants, some of which may possess novel host-colonizing and pathogenicity traits. In some plants, successive vegetative propagation of infected tissues and introduction of new genotypes of a virus by vector transmission allows for viral populations to increase in complexity for hundreds of years allowing co-replication and subsequent recombination of the multiple viral genotypes. Using a resequencing microarray, we examined a persistent infection by a Citrus tristeza virus (CTV) complex in citrus, a vegetatively propagated, globally important fruit crop, and found that the complex comprised three major and a number of minor genotypes. Subsequent deep sequencing analysis of the viral population confirmed the presence of the three major CTV genotypes and, in addition, revealed that the minor genotypes consisted of an extraordinarily large number of genetic variants generated by promiscuous recombination between the major genotypes. Further analysis provided evidence that some of the recombinants underwent subsequent divergence, further increasing the genotypic complexity. These data demonstrate that persistent infection of multiple viral genotypes within a host organism is sufficient to drive the large-scale production of viral genetic variants that may evolve into new and emerging viruses.",2007 Sep 19,"['Weng, Ziming', 'Barthelson, Roger', 'Gowda, Siddarame', 'Hilf, Mark E.', 'Dawson, William O.', 'Galbraith, David W.', 'Xiong, Zhongguo']",PLoS One,,,True
8d14b700a065187eb4d8b01e0e9b6e3e37e5d09b,PMC,Prediction of RNA Pseudoknots Using Heuristic Modeling with Mapping and Sequential Folding,http://dx.doi.org/10.1371/journal.pone.0000905,PMC1975678,17878940,CC BY,"Predicting RNA secondary structure is often the first step to determining the structure of RNA. Prediction approaches have historically avoided searching for pseudoknots because of the extreme combinatorial and time complexity of the problem. Yet neglecting pseudoknots limits the utility of such approaches. Here, an algorithm utilizing structure mapping and thermodynamics is introduced for RNA pseudoknot prediction that finds the minimum free energy and identifies information about the flexibility of the RNA. The heuristic approach takes advantage of the 5′ to 3′ folding direction of many biological RNA molecules and is consistent with the hierarchical folding hypothesis and the contact order model. Mapping methods are used to build and analyze the folded structure for pseudoknots and to add important 3D structural considerations. The program can predict some well known pseudoknot structures correctly. The results of this study suggest that many functional RNA sequences are optimized for proper folding. They also suggest directions we can proceed in the future to achieve even better results.",2007 Sep 19,"['Dawson, Wayne K.', 'Fujiwara, Kazuya', 'Kawai, Gota']",PLoS One,,,True
fb77f295f754abf6a7e99a90dad5626180c5b177,PMC,Prediction of RNA Pseudoknots Using Heuristic Modeling with Mapping and Sequential Folding,http://dx.doi.org/10.1371/journal.pone.0000905,PMC1975678,17878940,CC BY,"Predicting RNA secondary structure is often the first step to determining the structure of RNA. Prediction approaches have historically avoided searching for pseudoknots because of the extreme combinatorial and time complexity of the problem. Yet neglecting pseudoknots limits the utility of such approaches. Here, an algorithm utilizing structure mapping and thermodynamics is introduced for RNA pseudoknot prediction that finds the minimum free energy and identifies information about the flexibility of the RNA. The heuristic approach takes advantage of the 5′ to 3′ folding direction of many biological RNA molecules and is consistent with the hierarchical folding hypothesis and the contact order model. Mapping methods are used to build and analyze the folded structure for pseudoknots and to add important 3D structural considerations. The program can predict some well known pseudoknot structures correctly. The results of this study suggest that many functional RNA sequences are optimized for proper folding. They also suggest directions we can proceed in the future to achieve even better results.",2007 Sep 19,"['Dawson, Wayne K.', 'Fujiwara, Kazuya', 'Kawai, Gota']",PLoS One,,,True
898be097851a56d857d6cdb8ccbbdd3666eb4963,PMC,Prediction of RNA Pseudoknots Using Heuristic Modeling with Mapping and Sequential Folding,http://dx.doi.org/10.1371/journal.pone.0000905,PMC1975678,17878940,CC BY,"Predicting RNA secondary structure is often the first step to determining the structure of RNA. Prediction approaches have historically avoided searching for pseudoknots because of the extreme combinatorial and time complexity of the problem. Yet neglecting pseudoknots limits the utility of such approaches. Here, an algorithm utilizing structure mapping and thermodynamics is introduced for RNA pseudoknot prediction that finds the minimum free energy and identifies information about the flexibility of the RNA. The heuristic approach takes advantage of the 5′ to 3′ folding direction of many biological RNA molecules and is consistent with the hierarchical folding hypothesis and the contact order model. Mapping methods are used to build and analyze the folded structure for pseudoknots and to add important 3D structural considerations. The program can predict some well known pseudoknot structures correctly. The results of this study suggest that many functional RNA sequences are optimized for proper folding. They also suggest directions we can proceed in the future to achieve even better results.",2007 Sep 19,"['Dawson, Wayne K.', 'Fujiwara, Kazuya', 'Kawai, Gota']",PLoS One,,,True
c42f08c1803b6a13e7ff20041f34d336e4b0c7e9,PMC,Identification of new reference genes for the normalisation of canine osteoarthritic joint tissue transcripts from microarray data,http://dx.doi.org/10.1186/1471-2199-8-62,PMC1976117,17651481,CC BY,"BACKGROUND: Real-time reverse transcriptase quantitative polymerase chain reaction (real-time RT-qPCR) is the most accurate measure of gene expression in biological systems. The comparison of different samples requires the transformation of data through a process called normalisation. Reference or housekeeping genes are candidate genes which are selected on the basis of constitutive expression across samples, and allow the quantification of changes in gene expression. At present, no reference gene has been identified for any organism which is universally optimal for use across different tissue types or disease situations. We used microarray data to identify new reference genes generated from total RNA isolated from normal and osteoarthritic canine articular tissues (bone, ligament, cartilage, synovium and fat). RT-qPCR assays were designed and applied to each different articular tissue. Reference gene expression stability and ranking was compared using three different mathematical algorithms. RESULTS: Twelve new potential reference genes were identified from microarray data. One gene (mitochondrial ribosomal protein S7 [MRPS7]) was stably expressed in all five of the articular tissues evaluated. One gene HIRA interacting protein 5 isoform 2 [HIRP5]) was stably expressed in four of the tissues evaluated. A commonly used reference gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was not stably expressed in any of the tissues evaluated. Most consistent agreement between rank ordering of reference genes was observed between Bestkeeper© and geNorm, although each method tended to agree on the identity of the most stably expressed genes and the least stably expressed genes for each tissue. New reference genes identified using microarray data normalised in a conventional manner were more stable than those identified by microarray data normalised by using a real-time RT-qPCR methodology. CONCLUSION: Microarray data normalised by a conventional manner can be filtered using a simple stepwise procedure to identify new reference genes, some of which will demonstrate good measures of stability. Mitochondrial ribosomal protein S7 is a new reference gene worthy of investigation in other canine tissues and diseases. Different methods of reference gene stability assessment will generally agree on the most and least stably expressed genes, when co-regulation is not present.",2007 Jul 25,"['Maccoux, Lindsey J', 'Clements, Dylan N', 'Salway, Fiona', 'Day, Philip JR']",BMC Mol Biol,,,True
753d7438fe0a32b2c68985a255f92661145d46d2,PMC,Identification of Upper Respiratory Tract Pathogens Using Electrochemical Detection on an Oligonucleotide Microarray,http://dx.doi.org/10.1371/journal.pone.0000924,PMC1976596,17895966,CC0,"Bacterial and viral upper respiratory infections (URI) produce highly variable clinical symptoms that cannot be used to identify the etiologic agent. Proper treatment, however, depends on correct identification of the pathogen involved as antibiotics provide little or no benefit with viral infections. Here we describe a rapid and sensitive genotyping assay and microarray for URI identification using standard amplification and hybridization techniques, with electrochemical detection (ECD) on a semiconductor-based oligonucleotide microarray. The assay was developed to detect four bacterial pathogens (Bordetella pertussis, Streptococcus pyogenes, Chlamydia pneumoniae and Mycoplasma pneumoniae) and 9 viral pathogens (adenovirus 4, coronavirus OC43, 229E and HK, influenza A and B, parainfluinza types 1, 2, and 3 and respiratory syncytial virus. This new platform forms the basis for a fully automated diagnostics system that is very flexible and can be customized to suit different or additional pathogens. Multiple probes on a flexible platform allow one to test probes empirically and then select highly reactive probes for further iterative evaluation. Because ECD uses an enzymatic reaction to create electrical signals that can be read directly from the array, there is no need for image analysis or for expensive and delicate optical scanning equipment. We show assay sensitivity and specificity that are excellent for a multiplexed format.",2007 Sep 26,"['Lodes, Michael J.', 'Suciu, Dominic', 'Wilmoth, Jodi L.', 'Ross, Marty', 'Munro, Sandra', 'Dix, Kim', 'Bernards, Karen', 'Stöver, Axel G.', 'Quintana, Miguel', 'Iihoshi, Naomi', 'Lyon, Wanda J.', 'Danley, David L.', 'McShea, Andrew']",PLoS One,,,True
d1f82bd6a621efe50dc1888f875c82c7d948a547,PMC,A Diverse Group of Previously Unrecognized Human Rhinoviruses Are Common Causes of Respiratory Illnesses in Infants,http://dx.doi.org/10.1371/journal.pone.0000966,PMC1989136,17912345,CC BY,"BACKGROUND: Human rhinoviruses (HRVs) are the most prevalent human pathogens, and consist of 101 serotypes that are classified into groups A and B according to sequence variations. HRV infections cause a wide spectrum of clinical outcomes ranging from asymptomatic infection to severe lower respiratory symptoms. Defining the role of specific strains in various HRV illnesses has been difficult because traditional serology, which requires viral culture and neutralization tests using 101 serotype-specific antisera, is insensitive and laborious. METHODS AND FINDINGS: To directly type HRVs in nasal secretions of infants with frequent respiratory illnesses, we developed a sensitive molecular typing assay based on phylogenetic comparisons of a 260-bp variable sequence in the 5' noncoding region with homologous sequences of the 101 known serotypes. Nasal samples from 26 infants were first tested with a multiplex PCR assay for respiratory viruses, and HRV was the most common virus found (108 of 181 samples). Typing was completed for 101 samples and 103 HRVs were identified. Surprisingly, 54 (52.4%) HRVs did not match any of the known serotypes and had 12–35% nucleotide divergence from the nearest reference HRVs. Of these novel viruses, 9 strains (17 HRVs) segregated from HRVA, HRVB and human enterovirus into a distinct genetic group (“C”). None of these new strains could be cultured in traditional cell lines. CONCLUSIONS: By molecular analysis, over 50% of HRV detected in sick infants were previously unrecognized strains, including 9 strains that may represent a new HRV group. These findings indicate that the number of HRV strains is considerably larger than the 101 serotypes identified with traditional diagnostic techniques, and provide evidence of a new HRV group.",2007 Oct 3,"['Lee, Wai-Ming', 'Kiesner, Christin', 'Pappas, Tressa', 'Lee, Iris', 'Grindle, Kris', 'Jartti, Tuomas', 'Jakiela, Bogdan', 'Lemanske, Robert F.', 'Shult, Peter A.', 'Gern, James E.']",PLoS One,,,True
a1213a37009cf0d561bdfe620cbeabf8de2778d1,PMC,Conformational Reorganization of the SARS Coronavirus Spike Following Receptor Binding: Implications for Membrane Fusion,http://dx.doi.org/10.1371/journal.pone.0001082,PMC2034598,17957264,CC BY,"The SARS coronavirus (SARS-CoV) spike is the largest known viral spike molecule, and shares a similar function with all class 1 viral fusion proteins. Previous structural studies of membrane fusion proteins have largely used crystallography of static molecular fragments, in isolation of their transmembrane domains. In this study we have produced purified, irradiated SARS-CoV virions that retain their morphology, and are fusogenic in cell culture. We used cryo-electron microscopy and image processing to investigate conformational changes that occur in the entire spike of intact virions when they bind to the viral receptor, angiotensin-converting enzyme 2 (ACE2). We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. Furthermore, our results show that receptor binding and subsequent membrane fusion are distinct steps, and that each spike can bind up to three ACE2 molecules. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis.",2007 Oct 24,"['Beniac, Daniel R.', 'deVarennes, Shauna L.', 'Andonov, Anton', 'He, Runtao', 'Booth, Tim F.']",PLoS One,,,True
89cc8249f1595458ab949c3e6fad98dbb19a40d2,PMC,Non-pharmaceutical public health interventions for pandemic influenza: an evaluation of the evidence base,http://dx.doi.org/10.1186/1471-2458-7-208,PMC2040158,17697389,CC BY,"BACKGROUND: In an influenza pandemic, the benefit of vaccines and antiviral medications will be constrained by limitations on supplies and effectiveness. Non-pharmaceutical public health interventions will therefore be vital in curtailing disease spread. However, the most comprehensive assessments of the literature to date recognize the generally poor quality of evidence on which to base non-pharmaceutical pandemic planning decisions. In light of the need to prepare for a possible pandemic despite concerns about the poor quality of the literature, combining available evidence with expert opinion about the relative merits of non-pharmaceutical interventions for pandemic influenza may lead to a more informed and widely accepted set of recommendations. We evaluated the evidence base for non-pharmaceutical public health interventions. Then, based on the collective evidence, we identified a set of recommendations for and against interventions that are specific to both the setting in which an intervention may be used and the pandemic phase, and which can be used by policymakers to prepare for a pandemic until scientific evidence can definitively respond to planners' needs. METHODS: Building on reviews of past pandemics and recent historical inquiries, we evaluated the relative merits of non-pharmaceutical interventions by combining available evidence from the literature with qualitative and quantitative expert opinion. Specifically, we reviewed the recent scientific literature regarding the prevention of human-to-human transmission of pandemic influenza, convened a meeting of experts from multiple disciplines, and elicited expert recommendation about the use of non-pharmaceutical public health interventions in a variety of settings (healthcare facilities; community-based institutions; private households) and pandemic phases (no pandemic; no US pandemic; early localized US pandemic; advanced US pandemic). RESULTS: The literature contained a dearth of evidence on the efficacy or effectiveness of most non-pharmaceutical interventions for influenza. In an effort to inform decision-making in the absence of strong scientific evidence, the experts ultimately endorsed hand hygiene and respiratory etiquette, surveillance and case reporting, and rapid viral diagnosis in all settings and during all pandemic phases. They also encouraged patient and provider use of masks and other personal protective equipment as well as voluntary self-isolation of patients during all pandemic phases. Other non-pharmaceutical interventions including mask-use and other personal protective equipment for the general public, school and workplace closures early in an epidemic, and mandatory travel restrictions were rejected as likely to be ineffective, infeasible, or unacceptable to the public. CONCLUSION: The demand for scientific evidence on non-pharmaceutical public health interventions for influenza is pervasive, and present policy recommendations must rely heavily on expert judgment. In the absence of a definitive science base, our assessment of the evidence identified areas for further investigation as well as non-pharmaceutical public health interventions that experts believe are likely to be beneficial, feasible and widely acceptable in an influenza pandemic.",2007 Aug 15,"['Aledort, Julia E', 'Lurie, Nicole', 'Wasserman, Jeffrey', 'Bozzette, Samuel A']",BMC Public Health,,,True
1b401888b1faf175680ef5a940c16b14811c301a,PMC,Non-pharmaceutical public health interventions for pandemic influenza: an evaluation of the evidence base,http://dx.doi.org/10.1186/1471-2458-7-208,PMC2040158,17697389,CC BY,"BACKGROUND: In an influenza pandemic, the benefit of vaccines and antiviral medications will be constrained by limitations on supplies and effectiveness. Non-pharmaceutical public health interventions will therefore be vital in curtailing disease spread. However, the most comprehensive assessments of the literature to date recognize the generally poor quality of evidence on which to base non-pharmaceutical pandemic planning decisions. In light of the need to prepare for a possible pandemic despite concerns about the poor quality of the literature, combining available evidence with expert opinion about the relative merits of non-pharmaceutical interventions for pandemic influenza may lead to a more informed and widely accepted set of recommendations. We evaluated the evidence base for non-pharmaceutical public health interventions. Then, based on the collective evidence, we identified a set of recommendations for and against interventions that are specific to both the setting in which an intervention may be used and the pandemic phase, and which can be used by policymakers to prepare for a pandemic until scientific evidence can definitively respond to planners' needs. METHODS: Building on reviews of past pandemics and recent historical inquiries, we evaluated the relative merits of non-pharmaceutical interventions by combining available evidence from the literature with qualitative and quantitative expert opinion. Specifically, we reviewed the recent scientific literature regarding the prevention of human-to-human transmission of pandemic influenza, convened a meeting of experts from multiple disciplines, and elicited expert recommendation about the use of non-pharmaceutical public health interventions in a variety of settings (healthcare facilities; community-based institutions; private households) and pandemic phases (no pandemic; no US pandemic; early localized US pandemic; advanced US pandemic). RESULTS: The literature contained a dearth of evidence on the efficacy or effectiveness of most non-pharmaceutical interventions for influenza. In an effort to inform decision-making in the absence of strong scientific evidence, the experts ultimately endorsed hand hygiene and respiratory etiquette, surveillance and case reporting, and rapid viral diagnosis in all settings and during all pandemic phases. They also encouraged patient and provider use of masks and other personal protective equipment as well as voluntary self-isolation of patients during all pandemic phases. Other non-pharmaceutical interventions including mask-use and other personal protective equipment for the general public, school and workplace closures early in an epidemic, and mandatory travel restrictions were rejected as likely to be ineffective, infeasible, or unacceptable to the public. CONCLUSION: The demand for scientific evidence on non-pharmaceutical public health interventions for influenza is pervasive, and present policy recommendations must rely heavily on expert judgment. In the absence of a definitive science base, our assessment of the evidence identified areas for further investigation as well as non-pharmaceutical public health interventions that experts believe are likely to be beneficial, feasible and widely acceptable in an influenza pandemic.",2007 Aug 15,"['Aledort, Julia E', 'Lurie, Nicole', 'Wasserman, Jeffrey', 'Bozzette, Samuel A']",BMC Public Health,,,False
0bbe5dfd223ce7b53d68fb0dfc3286f5bd3fc404,PMC,Non-pharmaceutical public health interventions for pandemic influenza: an evaluation of the evidence base,http://dx.doi.org/10.1186/1471-2458-7-208,PMC2040158,17697389,CC BY,"BACKGROUND: In an influenza pandemic, the benefit of vaccines and antiviral medications will be constrained by limitations on supplies and effectiveness. Non-pharmaceutical public health interventions will therefore be vital in curtailing disease spread. However, the most comprehensive assessments of the literature to date recognize the generally poor quality of evidence on which to base non-pharmaceutical pandemic planning decisions. In light of the need to prepare for a possible pandemic despite concerns about the poor quality of the literature, combining available evidence with expert opinion about the relative merits of non-pharmaceutical interventions for pandemic influenza may lead to a more informed and widely accepted set of recommendations. We evaluated the evidence base for non-pharmaceutical public health interventions. Then, based on the collective evidence, we identified a set of recommendations for and against interventions that are specific to both the setting in which an intervention may be used and the pandemic phase, and which can be used by policymakers to prepare for a pandemic until scientific evidence can definitively respond to planners' needs. METHODS: Building on reviews of past pandemics and recent historical inquiries, we evaluated the relative merits of non-pharmaceutical interventions by combining available evidence from the literature with qualitative and quantitative expert opinion. Specifically, we reviewed the recent scientific literature regarding the prevention of human-to-human transmission of pandemic influenza, convened a meeting of experts from multiple disciplines, and elicited expert recommendation about the use of non-pharmaceutical public health interventions in a variety of settings (healthcare facilities; community-based institutions; private households) and pandemic phases (no pandemic; no US pandemic; early localized US pandemic; advanced US pandemic). RESULTS: The literature contained a dearth of evidence on the efficacy or effectiveness of most non-pharmaceutical interventions for influenza. In an effort to inform decision-making in the absence of strong scientific evidence, the experts ultimately endorsed hand hygiene and respiratory etiquette, surveillance and case reporting, and rapid viral diagnosis in all settings and during all pandemic phases. They also encouraged patient and provider use of masks and other personal protective equipment as well as voluntary self-isolation of patients during all pandemic phases. Other non-pharmaceutical interventions including mask-use and other personal protective equipment for the general public, school and workplace closures early in an epidemic, and mandatory travel restrictions were rejected as likely to be ineffective, infeasible, or unacceptable to the public. CONCLUSION: The demand for scientific evidence on non-pharmaceutical public health interventions for influenza is pervasive, and present policy recommendations must rely heavily on expert judgment. In the absence of a definitive science base, our assessment of the evidence identified areas for further investigation as well as non-pharmaceutical public health interventions that experts believe are likely to be beneficial, feasible and widely acceptable in an influenza pandemic.",2007 Aug 15,"['Aledort, Julia E', 'Lurie, Nicole', 'Wasserman, Jeffrey', 'Bozzette, Samuel A']",BMC Public Health,,,False
d4f8fcc4360079a02215dd83c280e4ff2b2363be,PMC,An evaluation of Comparative Genome Sequencing (CGS) by comparing two previously-sequenced bacterial genomes,http://dx.doi.org/10.1186/1471-2164-8-274,PMC2072959,17697331,CC BY,"BACKGROUND: With the development of new technology, it has recently become practical to resequence the genome of a bacterium after experimental manipulation. It is critical though to know the accuracy of the technique used, and to establish confidence that all of the mutations were detected. RESULTS: In order to evaluate the accuracy of genome resequencing using the microarray-based Comparative Genome Sequencing service provided by Nimblegen Systems Inc., we resequenced the E. coli strain W3110 Kohara using MG1655 as a reference, both of which have been completely sequenced using traditional sequencing methods. CGS detected 7 of 8 small sequence differences, one large deletion, and 9 of 12 IS element insertions present in W3110, but did not detect a large chromosomal inversion. In addition, we confirmed that CGS also detected 2 SNPs, one deletion and 7 IS element insertions that are not present in the genome sequence, which we attribute to changes that occurred after the creation of the W3110 lambda clone library. The false positive rate for SNPs was one per 244 Kb of genome sequence. CONCLUSION: CGS is an effective way to detect multiple mutations present in one bacterium relative to another, and while highly cost-effective, is prone to certain errors. Mutations occurring in repeated sequences or in sequences with a high degree of secondary structure may go undetected. It is also critical to follow up on regions of interest in which SNPs were not called because they often indicate deletions or IS element insertions.",2007 Aug 14,"['Herring, Christopher D', 'Palsson, Bernhard Ø']",BMC Genomics,,,True
ab1dfbe0d723b54d14e414d732fbedcd40adb021,PMC,Sharing H5N1 Viruses to Stop a Global Influenza Pandemic,http://dx.doi.org/10.1371/journal.pmed.0040330,PMC2080649,18031197,CC BY,"Indonesia's refusal to share samples of H5N1 virus with World Health Organization for most of 2007 is distressing and potentially dangerous for global public health, argue the authors.",2007 Nov 20,"['Garrett, Laurie', 'Fidler, David P']",PLoS Med,,,True
9992ffbec7c8256d057b05a858cde82d36d64ae3,PMC,Antibody-Based HIV-1 Vaccines: Recent Developments and Future Directions: A summary report from a Global HIV Vaccine Enterprise Working Group,http://dx.doi.org/10.1371/journal.pmed.0040348,PMC2100141,18052607,CC BY,The authors discuss humoral immune responses to HIV and approaches to designing vaccines that induce viral neutralizing and other potentially protective antibodies.,2007 Dec 1,"['Montefiori, David', 'Sattentau, Quentin', 'Flores, Jorge', 'Esparza, José', 'Mascola, John', None]",PLoS Med,,,True
63008713691bdb1d8eed016dbc54332f11d43739,PMC,Host Gene Expression Profiling of Dengue Virus Infection in Cell Lines and Patients,http://dx.doi.org/10.1371/journal.pntd.0000086,PMC2100376,18060089,CC BY,"BACKGROUND: Despite the seriousness of dengue-related disease, with an estimated 50–100 million cases of dengue fever and 250,000–500,000 cases of dengue hemorrhagic fever/dengue shock syndrome each year, a clear understanding of dengue pathogenesis remains elusive. Because of the lack of a disease model in animals and the complex immune interaction in dengue infection, the study of host response and immunopathogenesis is difficult. The development of genomics technology, microarray and high throughput quantitative PCR have allowed researchers to study gene expression changes on a much broader scale. We therefore used this approach to investigate the host response in dengue virus-infected cell lines and in patients developing dengue fever. METHODOLOGY/PRINCIPAL FINDINGS: Using microarray and high throughput quantitative PCR method to monitor the host response to dengue viral replication in cell line infection models and in dengue patient blood samples, we identified differentially expressed genes along three major pathways; NF-κB initiated immune responses, type I interferon (IFN) and the ubiquitin proteasome pathway. Among the most highly upregulated genes were the chemokines IP-10 and I-TAC, both ligands of the CXCR3 receptor. Increased expression of IP-10 and I-TAC in the peripheral blood of ten patients at the early onset of fever was confirmed by ELISA. A highly upregulated gene in the IFN pathway, viperin, was overexpressed in A549 cells resulting in a significant reduction in viral replication. The upregulation of genes in the ubiquitin-proteasome pathway prompted the testing of proteasome inhibitors MG-132 and ALLN, both of which reduced viral replication. CONCLUSION/SIGNIFICANCE: Unbiased gene expression analysis has identified new host genes associated with dengue infection, which we have validated in functional studies. We showed that some parts of the host response can be used as potential biomarkers for the disease while others can be used to control dengue viral replication, thus representing viable targets for drug therapy.",2007 Nov 21,"['Fink, Joshua', 'Gu, Feng', 'Ling, Ling', 'Tolfvenstam, Thomas', 'Olfat, Farzad', 'Chin, Keh Chuang', 'Aw, Pauline', 'George, Joshy', 'Kuznetsov, Vladimir A.', 'Schreiber, Mark', 'Vasudevan, Subhash G.', 'Hibberd, Martin L.']",PLoS Negl Trop Dis,,,True
0e046152bb9c537c62ed4c4616a0b627ccfc992a,PMC,Rapid generation of an anthrax immunotherapeutic from goats using a novel non-toxic muramyl dipeptide adjuvant,http://dx.doi.org/10.1186/1476-8518-5-11,PMC2104530,17953756,CC BY,"BACKGROUND: There is a clear need for vaccines and therapeutics for potential biological weapons of mass destruction and emerging diseases. Anthrax, caused by the bacterium Bacillus anthracis, has been used as both a biological warfare agent and bioterrorist weapon previously. Although antibiotic therapy is effective in the early stages of anthrax infection, it does not have any effect once exposed individuals become symptomatic due to B. anthracis exotoxin accumulation. The bipartite exotoxins are the major contributing factors to the morbidity and mortality observed in acute anthrax infections. METHODS: Using recombinant B. anthracis protective antigen (PA83), covalently coupled to a novel non-toxic muramyl dipeptide (NT-MDP) derivative we hyper-immunized goats three times over the course of 14 weeks. Goats were plasmapheresed and the IgG fraction (not affinity purified) and F(ab')(2 )derivatives were characterized in vitro and in vivo for protection against lethal toxin mediated intoxication. RESULTS: Anti-PA83 IgG conferred 100% protection at 7.5 μg in a cell toxin neutralization assay. Mice exposed to 5 LD(50 )of Bacillus anthracis Ames spores by intranares inoculation demonstrated 60% survival 14 d post-infection when administered a single bolus dose (32 mg/kg body weight) of anti-PA83 IgG at 24 h post spore challenge. Anti-PA83 F(ab')(2 )fragments retained similar neutralization and protection levels both in vitro and in vivo. CONCLUSION: The protection afforded by these GMP-grade caprine immunotherapeutics post-exposure in the pilot murine model suggests they could be used effectively to treat post-exposure, symptomatic human anthrax patients following a bioterrorism event. These results also indicate that recombinant PA83 coupled to NT-MDP is a potent inducer of neutralizing antibodies and suggest it would be a promising vaccine candidate for anthrax. The ease of production, ease of covalent attachment, and immunostimulatory activity of the NT-MDP indicate it would be a superior adjuvant to alum or other traditional adjuvants in vaccine formulations.",2007 Oct 22,"['Kelly, Cassandra D', ""O'Loughlin, Chris"", 'Gelder, Frank B', 'Peterson, Johnny W', 'Sower, Laurie E', 'Cirino, Nick M']",J Immune Based Ther Vaccines,,,True
6a0f0170d5ad8bb5c0f2af642c0fc37e48dbd3a4,PMC,Species-specific evolution of immune receptor tyrosine based activation motif-containing CEACAM1-related immune receptors in the dog,http://dx.doi.org/10.1186/1471-2148-7-196,PMC2110893,17945019,CC BY,"BACKGROUND: Although the impact of pathogens on the evolution of the mammalian immune system is still under debate, proteins, which both regulate immune responses and serve as cellular receptors for pathogens should be at the forefront of pathogen-driven host evolution. The CEA (carcinoembryonic antigen) gene family codes for such proteins and indeed shows tremendous species-specific variation between human and rodents. Since little is known about the CEA gene family in other lineages of placental mammals, we expected to gain new insights into the evolution of the rapidly diverging CEA family by analyzing the CEA family of the dog. RESULTS: Here we describe the complete CEA gene family in the dog. We found that the gene coding for the ITIM-bearing immunoregulatory molecule CEACAM1 gave rise to a recent expansion of the canine CEA gene family by gene duplication, similar to that previously found in humans and mice. However, while the murine and human CEACAMs (carcinoembryonic antigen-related cell adhesion molecules) are predominantly secreted and GPI-anchored, respectively, in the dog, most of the CEACAMs represent ITAM-bearing transmembrane proteins. One of these proteins, CEACAM28, exhibits nearly complete sequence identity with the ligand-binding N domain of CEACAM1, but antagonizing signaling motifs in the cytoplasmic tail. Comparison of nonsynonymous and synonymous substitutions indicates that the CEACAM28 N domain is under the strongest purifying selection of all canine CEACAM1-related CEACAMs. In addition, CEACAM28 shows a similar expression pattern in resting immune cells and tissues as CEACAM1. However, upon activation CEACAM28 mRNA and CEACAM1 mRNA are differentially regulated. CONCLUSION: Thus, CEACAM1 and CEACAM28 are the first paired immune receptors identified within the CEA gene family, which are expressed on T cells and are most likely involved in the fine-tuning of T cell responses. The direction of gene conversion accompanied by purifying selection and expression in immune cells suggests the possibility that CEACAM28 evolved in response to selective pressure imposed by species-specific pathogens.",2007 Oct 18,"['Kammerer, Robert', 'Popp, Tanja', 'Härtle, Stefan', 'Singer, Bernhard B', 'Zimmermann, Wolfgang']",BMC Evol Biol,,,True
296e24d0dc3c17633eeffea57bd23e968a1c8a5e,PMC,Elevated adipogenesis of marrow mesenchymal stem cells during early steroid-associated osteonecrosis development,http://dx.doi.org/10.1186/1749-799X-2-15,PMC2146995,17937789,CC BY,"BACKGROUND: Increased bone marrow lipid deposition in steroid-associated osteonecrosis (ON) implies that abnormalities in fat metabolism play an important role in ON development. The increase in lipid deposition might be explained by elevated adipogenesis of marrow mesenchymal stem cells (MSCs). However, it remains unclear whether there is a close association between elevated adipogenesis and steroid-associated ON development. OBJECTIVE: The present study was designed to test the hypothesis that there might be a close association between elevated adipogenesis and steroid-associated ON development. METHODS: ON rabbit model was induced based on our established protocol. Dynamic-MRI was employed for local intra-osseous perfusion evaluation in bilateral femora. Two weeks after induction, bone marrow was harvested for evaluating the ability of adipogenic differentiation of marrow MSCs at both cellular and mRNA level involving adipogenesis-related gene peroxisome proliferator-activated receptor gamma2 (PPARγ2). The bilateral femora were dissected for examining marrow lipid deposition by quantifying fat cell number, fat cell size, lipid deposition area and ON lesions. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON occurrence, the rabbits were divided into ON(+ )(with at least one ON lesion) group and ON(- )(without ON lesion) group. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON extension, the ON(+ )rabbits were further divided into sub-single-lesion group (SON group: with one ON lesion) and sub-multiple-lesion group (MON group: with more than one ON lesion). RESULTS: Local intra-osseous perfusion index was found lower in either ON(+ )or MON group when compared to either ON(- )or SON group, whereas the marrow fat cells number and area were much larger in either ON(+ )or MON group as compared with ON(- )and SON group. The adipogenic differentiation ability of MSCs and PPARγ2 expression in either ON(+ )or MON group were elevated significantly as compared with either ON(- )or SON group. CONCLUSION: These findings support our hypothesis that there is a close association between elevated adipogenesis and steroid-associated osteonecrosis development.",2007 Oct 15,"['Sheng, Hui H', 'Zhang, Ge G', 'Cheung, Wing Hoi WH', 'Chan, Chun Wai CW', 'Wang, Yi Xiang YX', 'Lee, Kwong Man KM', 'Wang, Hong Fu HF', 'Leung, Kwok Sui KS', 'Qin, Ling L']",J Orthop Surg,,,True
e45d3e45dd952470cbbac928b949fc6339e3ec81,PMC,Saccharomyces cerevisiae: a versatile eukaryotic system in virology,http://dx.doi.org/10.1186/1475-2859-6-32,PMC2148055,17927824,CC BY,"The yeast Saccharomyces cerevisiae is a well-established model system for understanding fundamental cellular processes relevant to higher eukaryotic organisms. Less known is its value for virus research, an area in which Saccharomyces cerevisiae has proven to be very fruitful as well. The present review will discuss the main achievements of yeast-based studies in basic and applied virus research. These include the analysis of the function of individual proteins from important pathogenic viruses, the elucidation of key processes in viral replication through the development of systems that allow the replication of higher eukayotic viruses in yeast, and the use of yeast in antiviral drug development and vaccine production.",2007 Oct 10,"['Galao, Rui P', 'Scheller, Nicoletta', 'Alves-Rodrigues, Isabel', 'Breinig, Tanja', 'Meyerhans, Andreas', 'Díez, Juana']",Microb Cell Fact,,,True
2c5d1ebec404ad8061eb81e94effbe52a6dbe809,PMC,Receptor-Induced Thiolate Couples Env Activation to Retrovirus Fusion and Infection,http://dx.doi.org/10.1371/journal.ppat.0030198,PMC2151085,18260686,CC BY,"According to current models of retrovirus infection, receptor binding to the surface subunit (SU) of the envelope glycoprotein (Env) triggers a conformational change in the transmembrane subunit (TM) that mediates virus fusion to cell membranes. To understand how this occurs, we investigated the role of the receptor Tva in avian leukosis virus-A (ALV-A) infection. We find that Tva binding induced the formation of a reactive thiolate on Cys38 (Cys38-S(−)) in SU. Both chemical and genetic inactivation of Cys38-S(−) completely abrogated ALV fusion and infection. Remarkably, Cys38-S(−) does not mediate isomerization of the SU-TM disulfide bond and is not required for Tva-induced activation of TM, including pre-hairpin association with membranes and low pH assembly of helical bundles. These findings indicate that, contrary to current models, receptor activation of TM is not sufficient for ALV fusion and infection and that formation of a reactive thiolate is an additional receptor-dependent step.",2007 Dec 21,"['Smith, Jason G', 'Cunningham, James M']",PLoS Pathog,,,True
8a18be6bbec92094276f843c39fa9ea509e20215,PMC,"Plague: Past, Present, and Future",http://dx.doi.org/10.1371/journal.pmed.0050003,PMC2194748,18198939,CC0,The authors argue that plague should be taken much more seriously by the international health community.,2008 Jan 15,"['Stenseth, Nils Chr', 'Atshabar, Bakyt B', 'Begon, Mike', 'Belmain, Steven R', 'Bertherat, Eric', 'Carniel, Elisabeth', 'Gage, Kenneth L', 'Leirs, Herwig', 'Rahalison, Lila']",PLoS Med,,,True
7a0851e43f82ced2223468ad1280a914fed947b2,PMC,"Plague: Past, Present, and Future",http://dx.doi.org/10.1371/journal.pmed.0050003,PMC2194748,18198939,CC0,The authors argue that plague should be taken much more seriously by the international health community.,2008 Jan 15,"['Stenseth, Nils Chr', 'Atshabar, Bakyt B', 'Begon, Mike', 'Belmain, Steven R', 'Bertherat, Eric', 'Carniel, Elisabeth', 'Gage, Kenneth L', 'Leirs, Herwig', 'Rahalison, Lila']",PLoS Med,,,True
99da41d8c3a3aebdaf5d889c3958181ae52ff6a9,PMC,"Plague: Past, Present, and Future",http://dx.doi.org/10.1371/journal.pmed.0050003,PMC2194748,18198939,CC0,The authors argue that plague should be taken much more seriously by the international health community.,2008 Jan 15,"['Stenseth, Nils Chr', 'Atshabar, Bakyt B', 'Begon, Mike', 'Belmain, Steven R', 'Bertherat, Eric', 'Carniel, Elisabeth', 'Gage, Kenneth L', 'Leirs, Herwig', 'Rahalison, Lila']",PLoS Med,,,True
139b81bc9c99d76cffc2014c4851942d2f592950,PMC,Modeling and detection of respiratory-related outbreak signatures,http://dx.doi.org/10.1186/1472-6947-7-28,PMC2203979,17919318,CC BY,"BACKGROUND: Time series methods are commonly used to detect disease outbreak signatures (e.g., signals due to influenza outbreaks and anthrax attacks) from varying respiratory-related diagnostic or syndromic data sources. Typically this involves two components: (i) Using time series methods to model the baseline background distribution (the time series process that is assumed to contain no outbreak signatures), (ii) Detecting outbreak signatures using filter-based time series methods. METHODS: We consider time series models for chest radiograph data obtained from Midwest children's emergency departments. These models incorporate available covariate information such as patient visit counts and smoothed ambient temperature series, as well as time series dependencies on daily and weekly seasonal scales. Respiratory-related outbreak signature detection is based on filtering the one-step-ahead prediction errors obtained from the time series models for the respiratory-complaint background. RESULTS: Using simulation experiments based on a stochastic model for an anthrax attack, we illustrate the effect of the choice of filter and the statistical models upon radiograph-attributed outbreak signature detection. CONCLUSION: We demonstrate the importance of using seasonal autoregressive integrated average time series models (SARIMA) with covariates in the modeling of respiratory-related time series data. We find some homogeneity in the time series models for the respiratory-complaint backgrounds across the Midwest emergency departments studied. Our simulations show that the balance between specificity, sensitivity, and timeliness to detect an outbreak signature differs by the emergency department and the choice of filter. The linear and exponential filters provide a good balance.",2007 Oct 5,"['Craigmile, Peter F', 'Kim, Namhee', 'Fernandez, Soledad A', 'Bonsu, Bema K']",BMC Med Inform Decis Mak,,,True
8d355f050721e1e9d9288c7824cc38546b6ef2a6,PMC,The costs of preventing the spread of respiratory infection in family physician offices: a threshold analysis,http://dx.doi.org/10.1186/1472-6963-7-181,PMC2204002,17999757,CC BY,"BACKGROUND: Influenza poses concerns about epidemic respiratory infection. Interventions designed to prevent the spread of respiratory infection within family physician (FP) offices could potentially have a significant positive influence on the health of Canadians. The main purpose of this paper is to estimate the explicit costs of such an intervention. METHODS: A cost analysis of a respiratory infection control was conducted. The costs were estimated from the perspective of provincial government. In addition, a threshold analysis was conducted to estimate a threshold value of the intervention's effectiveness that could generate potential savings in terms of averted health-care costs by the intervention that exceed the explicit costs. The informational requirements for these implicit costs savings are high, however. Some of these elements, such as the cost of hospitalization in the event of contacting influenza, and the number of patients passing through the physicians' office, were readily available. Other pertinent points of information, such as the proportion of infected people who require hospitalization, could be imported from the existing literature. We take an indirect approach to calculate a threshold value for the most uncertain piece of information, namely the reduction in the probability of the infection spreading as a direct result of the intervention, at which the intervention becomes worthwhile. RESULTS: The 5-week intervention costs amounted to a total of $52,810.71, or $131,094.73 prorated according to the length of the flu season, or $512,729.30 prorated for the entire calendar year. The variable costs that were incurred for this 5-week project amounted to approximately $923.16 per participating medical practice. The (fixed) training costs per practice were equivalent to $73.27 for the 5-week intervention, or $28.14 for 13-week flu season, or $7.05 for an entire one-year period. CONCLUSION: Based on our conservative estimates for the direct cost savings, there are indications that the outreach facilitation intervention program would be cost effective if it can achieve a reduction in the probability of infection on the order of 0.83 (0.77, 1.05) percentage points. A facilitation intervention initiative tailored to the environment and needs of the family medical practice and walk-in clinics is of promise for improving respiratory infection control in the physicians' offices.",2007 Nov 13,"['Hogg, William', 'Gray, David', 'Huston, Patricia', 'Zhang, Wei']",BMC Health Serv Res,,,True
26b43aa70c7a8314456956b5ada051dc6807dc56,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,True
69f030af7402d525617886c4ab8a9bbe413c01c0,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,False
05a3101918abeee449871529fb0b788dd90df479,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,True
5978486a06f337a76f6dda4dec594be3fac4d646,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,False
4b88c761100af90fc95bc20644cbf9dda06febb1,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,False
a24f5d43a265d352f8aafdde4d2f7369ff4d49d5,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,False
f83cf1bf40760964918e556f51bf628891da95e5,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,False
28e3c0e0e0dbbf0d60f6033ef5254c5ccf138b37,PMC,Optimal design and validation of antiviral siRNA for targeting HIV-1,http://dx.doi.org/10.1186/1742-4690-4-80,PMC2204037,17996047,CC BY,"We propose rational designing of antiviral short-interfering RNA (siRNA) targeting highly divergent HIV-1. In this study, conserved regions within HIV-1 genomes were identified through an exhaustive computational analysis, and the functionality of siRNAs targeting the highest possible conserved regions was validated. We present several promising antiviral siRNA candidates that effectively inhibited multiple subtypes of HIV-1 by targeting the best conserved regions in pandemic HIV-1 group M strains.",2007 Nov 8,"['Naito, Yuki', 'Nohtomi, Kyoko', 'Onogi, Toshinari', 'Uenishi, Rie', 'Ui-Tei, Kumiko', 'Saigo, Kaoru', 'Takebe, Yutaka']",Retrovirology,,,False
5abea4a5497c9cfa476bf766b8360f73c12e8122,PMC,Coronavirus Spike Protein Inhibits Host Cell Translation by Interaction with eIF3f,http://dx.doi.org/10.1371/journal.pone.0001494,PMC2204050,18231581,CC BY,"In response to viral infection, the expression of numerous host genes, including predominantly a number of proinflammatory cytokines and chemokines, is usually up-regulated at both transcriptional and translational levels. It was noted that in cells infected with coronavirus, transcription and translation of some of these genes were differentially induced. Drastic induction of their expression at the transcriptional level was observed in cells infected with coronavirus. However, induction of the same genes at the translational level was usually found to be minimal to moderate. To investigate the underlying mechanisms, yeast two-hybrid screen was carried out using SARS-CoV proteins as baits, revealing that a subunit of the eukaryotic initiation factor 3 (eIF3), eIF3f, may interact with the N-terminal region of the SARS-CoV spike (S) protein. This interaction was subsequently confirmed by co-immunoprecipitation and immunofluorescent staining. Meanwhile, parallel experiments confirmed that eIF3f could also interact with the S protein of another coronavirus, the avian coronavirus infectious bronchitis virus (IBV). These interactions led to the inhibition of translation of a reporter gene in both in vitro expression system and intact cells. Interestingly, IBV-infected cells stably expressing a Flag-tagged eIF3f showed much higher translation of IL-6 and IL-8, suggesting that the interaction between coronavirus S protein and eIF3f plays a functional role in controlling the expression of host genes, especially genes that are induced during coronavirus infection cycles. This study reveals a novel mechanism exploited by coronavirus to regulate viral pathogenesis.",2008 Jan 30,"['Xiao, Han', 'Xu, Ling Hui', 'Yamada, Yoshiyuki', 'Liu, Ding Xiang']",PLoS One,,,True
16ffa1f7efaf96880e6f3c22d2de9c5672169303,PMC,Transmissibility of the Influenza Virus in the 1918 Pandemic,http://dx.doi.org/10.1371/journal.pone.0001498,PMC2204055,18231585,CC BY,"BACKGROUND: With a heightened increase in concern for an influenza pandemic we sought to better understand the 1918 Influenza pandemic, the most devastating epidemic of the previous century. METHODOLOGY/PRINCIPAL FINDINGS: We use data from several communities in Maryland, USA as well as two ships that experienced well-documented outbreaks of influenza in 1918. Using a likelihood-based method and a nonparametric method, we estimate the serial interval and reproductive number throughout the course of each outbreak. This analysis shows the basic reproductive number to be slightly lower in the Maryland communities (between 1.34 and 3.21) than for the enclosed populations on the ships (R(0) = 4.97, SE = 3.31). Additionally the effective reproductive number declined to sub epidemic levels more quickly on the ships (within around 10 days) than in the communities (within 30–40 days). The mean serial interval for the ships was consistent (3.33, SE = 5.96 and 3.81, SE = 3.69), while the serial intervals in the communities varied substantially (between 2.83, SE = 0.53 and 8.28, SE = 951.95). CONCLUSIONS/SIGNIFICANCE: These results illustrate the importance of considering the population dynamics when making statements about the epidemiological parameters of Influenza. The methods that we employ for estimation of the reproductive numbers and the serial interval can be easily replicated in other populations and with other diseases.",2008 Jan 30,"['White, Laura Forsberg', 'Pagano, Marcello']",PLoS One,,,True
c899a0907dc026208ece3df9c6d4b3c909c6dd46,PMC,"Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study",http://dx.doi.org/10.1186/cc5723,PMC2206456,17362525,CC BY,"INTRODUCTION: Accurate and timely diagnosis of community-acquired bacterial infections in patients with systemic inflammation remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival. We therefore compared the diagnostic characteristics of novel and routinely used biomarkers of sepsis alone and in combination. METHODS: This prospective cohort study included patients with systemic inflammatory response syndrome who were suspected of having community-acquired infections. It was conducted in a medical emergency department and department of infectious diseases at a university hospital. A multiplex immunoassay measuring soluble urokinase-type plasminogen activator (suPAR) and soluble triggering receptor expressed on myeloid cells (sTREM)-1 and macrophage migration inhibitory factor (MIF) was used in parallel with standard measurements of C-reactive protein (CRP), procalcitonin (PCT), and neutrophils. Two composite markers were constructed – one including a linear combination of the three best performing markers and another including all six – and the area under the receiver operating characteristic curve (AUC) was used to compare their performance and those of the individual markers. RESULTS: A total of 151 patients were eligible for analysis. Of these, 96 had bacterial infections. The AUCs for detection of a bacterial cause of inflammation were 0.50 (95% confidence interval [CI] 0.40 to 0.60) for suPAR, 0.61 (95% CI 0.52 to 0.71) for sTREM-1, 0.63 (95% CI 0.53 to 0.72) for MIF, 0.72 (95% CI 0.63 to 0.79) for PCT, 0.74 (95% CI 0.66 to 0.81) for neutrophil count, 0.81 (95% CI 0.73 to 0.86) for CRP, 0.84 (95% CI 0.71 to 0.91) for the composite three-marker test, and 0.88 (95% CI 0.81 to 0.92) for the composite six-marker test. The AUC of the six-marker test was significantly greater than that of the single markers. CONCLUSION: Combining information from several markers improves diagnostic accuracy in detecting bacterial versus nonbacterial causes of inflammation. Measurements of suPAR, sTREM-1 and MIF had limited value as single markers, whereas PCT and CRP exhibited acceptable diagnostic characteristics. TRIAL REGISTRATION: NCT 00389337",2007 Mar 16,"['Kofoed, Kristian', 'Andersen, Ove', 'Kronborg, Gitte', 'Tvede, Michael', 'Petersen, Janne', 'Eugen-Olsen, Jesper', 'Larsen, Klaus']",Crit Care,,,True
e035002c8135dab46801a3fc8a43b87240dbef8d,PMC,Predictability and epidemic pathways in global outbreaks of infectious diseases: the SARS case study,http://dx.doi.org/10.1186/1741-7015-5-34,PMC2213648,18031574,CC BY,"BACKGROUND: The global spread of the severe acute respiratory syndrome (SARS) epidemic has clearly shown the importance of considering the long-range transportation networks in the understanding of emerging diseases outbreaks. The introduction of extensive transportation data sets is therefore an important step in order to develop epidemic models endowed with realism. METHODS: We develop a general stochastic meta-population model that incorporates actual travel and census data among 3 100 urban areas in 220 countries. The model allows probabilistic predictions on the likelihood of country outbreaks and their magnitude. The level of predictability offered by the model can be quantitatively analyzed and related to the appearance of robust epidemic pathways that represent the most probable routes for the spread of the disease. RESULTS: In order to assess the predictive power of the model, the case study of the global spread of SARS is considered. The disease parameter values and initial conditions used in the model are evaluated from empirical data for Hong Kong. The outbreak likelihood for specific countries is evaluated along with the emerging epidemic pathways. Simulation results are in agreement with the empirical data of the SARS worldwide epidemic. CONCLUSION: The presented computational approach shows that the integration of long-range mobility and demographic data provides epidemic models with a predictive power that can be consistently tested and theoretically motivated. This computational strategy can be therefore considered as a general tool in the analysis and forecast of the global spreading of emerging diseases and in the definition of containment policies aimed at reducing the effects of potentially catastrophic outbreaks.",2007 Nov 21,"['Colizza, Vittoria', 'Barrat, Alain', 'Barthélemy, Marc', 'Vespignani, Alessandro']",BMC Med,,,True
59f7edc22693dec7a22ed949597d2bbc06002325,PMC,Predictability and epidemic pathways in global outbreaks of infectious diseases: the SARS case study,http://dx.doi.org/10.1186/1741-7015-5-34,PMC2213648,18031574,CC BY,"BACKGROUND: The global spread of the severe acute respiratory syndrome (SARS) epidemic has clearly shown the importance of considering the long-range transportation networks in the understanding of emerging diseases outbreaks. The introduction of extensive transportation data sets is therefore an important step in order to develop epidemic models endowed with realism. METHODS: We develop a general stochastic meta-population model that incorporates actual travel and census data among 3 100 urban areas in 220 countries. The model allows probabilistic predictions on the likelihood of country outbreaks and their magnitude. The level of predictability offered by the model can be quantitatively analyzed and related to the appearance of robust epidemic pathways that represent the most probable routes for the spread of the disease. RESULTS: In order to assess the predictive power of the model, the case study of the global spread of SARS is considered. The disease parameter values and initial conditions used in the model are evaluated from empirical data for Hong Kong. The outbreak likelihood for specific countries is evaluated along with the emerging epidemic pathways. Simulation results are in agreement with the empirical data of the SARS worldwide epidemic. CONCLUSION: The presented computational approach shows that the integration of long-range mobility and demographic data provides epidemic models with a predictive power that can be consistently tested and theoretically motivated. This computational strategy can be therefore considered as a general tool in the analysis and forecast of the global spreading of emerging diseases and in the definition of containment policies aimed at reducing the effects of potentially catastrophic outbreaks.",2007 Nov 21,"['Colizza, Vittoria', 'Barrat, Alain', 'Barthélemy, Marc', 'Vespignani, Alessandro']",BMC Med,,,False
910f8cb2d8f7ceb37d996bcbf327b4f5b26ed6d5,PMC,Determination of suitable housekeeping genes for normalisation of quantitative real time PCR analysis of cells infected with human immunodeficiency virus and herpes viruses,http://dx.doi.org/10.1186/1743-422X-4-130,PMC2216015,18053162,CC BY,"The choice of an appropriate housekeeping gene for normalisation purposes has now become an essential requirement when designing QPCR experiments. This is of particular importance when using QPCR to measure viral and cellular gene transcription levels in the context of viral infections as viruses can significantly interfere with host cell pathways, the components of which traditional housekeeping genes often encode. In this study we have determined the reliability of 10 housekeeping genes in context of four heavily studied viral infections; human immunodeficiency virus type 1, herpes simplex virus type 1, cytomegalovirus and varicella zoster virus infections using a variety of cell types and virus strains. This provides researchers of these viruses with a shortlist of potential housekeeping genes to use as normalisers for QPCR experiments.",2007 Dec 3,"['Watson, Sarah', 'Mercier, Sarah', 'Bye, Chris', 'Wilkinson, John', 'Cunningham, Anthony L', 'Harman, Andrew N']",Virol J,,,True
ab1f467d067233119dcffc5c542a88cbd7794397,PMC,"C-ME: A 3D Community-Based, Real-Time Collaboration Tool for Scientific Research and Training",http://dx.doi.org/10.1371/journal.pone.0001621,PMC2229842,18286178,CC BY,"The need for effective collaboration tools is growing as multidisciplinary proteome-wide projects and distributed research teams become more common. The resulting data is often quite disparate, stored in separate locations, and not contextually related. Collaborative Molecular Modeling Environment (C-ME) is an interactive community-based collaboration system that allows researchers to organize information, visualize data on a two-dimensional (2-D) or three-dimensional (3-D) basis, and share and manage that information with collaborators in real time. C-ME stores the information in industry-standard databases that are immediately accessible by appropriate permission within the computer network directory service or anonymously across the internet through the C-ME application or through a web browser. The system addresses two important aspects of collaboration: context and information management. C-ME allows a researcher to use a 3-D atomic structure model or a 2-D image as a contextual basis on which to attach and share annotations to specific atoms or molecules or to specific regions of a 2-D image. These annotations provide additional information about the atomic structure or image data that can then be evaluated, amended or added to by other project members.",2008 Feb 20,"['Kolatkar, Anand', 'Kennedy, Kevin', 'Halabuk, Dan', 'Kunken, Josh', 'Marrinucci, Dena', 'Bethel, Kelly', 'Guzman, Rodney', 'Huckaby, Tim', 'Kuhn, Peter']",PLoS One,,,True
7d7dbaff8c306dacea117552f6c97cb0b2b79ce3,PMC,Leptospirosis vaccines,http://dx.doi.org/10.1186/1475-2859-6-39,PMC2231387,18072968,CC BY,"Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP) vaccines, lipopolysaccharide (LPS) vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.",2007 Dec 11,"['Wang, Zhijun', 'Jin, Li', 'Węgrzyn, Alicja']",Microb Cell Fact,,,True
9d0ae9643da1b47c2234dd758a36ed3c3abc1aa2,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,True
cc724dd07268172a4d5b9d83df29fe32757dee98,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,True
0ed28158b9c944a36a22e6bb70ced547b0755ce3,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
8af5e1ddf29c2597dc841ca2d98f66947c232efb,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
4fbdae4fb7137b1db67c84619a04c7e4450a99fc,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
edbbf63540091284b702964a7c675bed500ec6ff,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
00ab80b71e43170669f4d5e762e102955e8e65d2,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
45897239ea14ad999550f9658168e4c59f7a64c8,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
5745f2adfd8f187f6d80ff4b6107e4c98c4fdade,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
1c189a9d2d493dff4bc906c03d5543dd7569d85d,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
0fc2fd4157d793fbcbb1b155c62f6e051a629b2d,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
368f95b18acbb5d7ac2c3fc58a2256e356b14212,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
35446cde6846ab1bf25e5e4db69ef202ac2e6043,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
452bccd188bdb4d74dafecdb234f031d822b084c,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
a7b6a9784c14b8fd02756ceaeb5c722095ae40be,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
fe2946af76126343fa6398ee9101da1b84f75a24,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
f0af5c3c75acfecfb4f50efe03b16cd3fced7b80,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
7d18def448c40e3f7a9e1875ed3a641306c95b00,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
a5edf71b28d875a8c2761850356e0ed5b62e3265,PMC,Mechanisms of GII.4 Norovirus Persistence in Human Populations,http://dx.doi.org/10.1371/journal.pmed.0050031,PMC2235898,18271619,CC0,"BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.",2008 Feb 12,"['Lindesmith, Lisa C', 'Donaldson, Eric F', 'LoBue, Anna D', 'Cannon, Jennifer L', 'Zheng, Du-Ping', 'Vinje, Jan', 'Baric, Ralph S']",PLoS Med,,,False
44f3796bf7bdaa361b977d350bc71190b31cf558,PMC,Analysis and prediction of protective continuous B-cell epitopes on pathogen proteins,http://dx.doi.org/10.1186/1745-7580-4-1,PMC2244602,18179690,CC BY,"BACKGROUND: The application of peptide based diagnostics and therapeutics mimicking part of protein antigen is experiencing renewed interest. So far selection and design rationale for such peptides is usually driven by T-cell epitope prediction, available experimental and modelled 3D structure, B-cell epitope predictions such as hydrophilicity plots or experience. If no structure is available the rational selection of peptides for the production of functionally altering or neutralizing antibodies is practically impossible. Specifically if many alternative antigens are available the reduction of required synthesized peptides until one successful candidate is found is of central technical interest. We have investigated the integration of B-cell epitope prediction with the variability of antigen and the conservation of patterns for post-translational modification (PTM) prediction to improve over state of the art in the field. In particular the application of machine-learning methods shows promising results. RESULTS: We find that protein regions leading to the production of functionally altering antibodies are often characterized by a distinct increase in the cumulative sum of three presented parameters. Furthermore the concept to maximize antigenicity, minimize variability and minimize the likelihood of post-translational modification for the identification of relevant sites leads to biologically interesting observations. Primarily, for about 50% of antigen the approach works well with individual area under the ROC curve (AROC) values of at least 0.65. On the other hand a significant portion reveals equivalently low AROC values of < = 0.35 indicating an overall non-Gaussian distribution. While about a third of 57 antigens are seemingly intangible by our approach our results suggest the existence of at least two distinct classes of bioinformatically detectable epitopes which should be predicted separately. As a side effect of our study we present a hand curated dataset for the validation of protectivity classification. Based on this dataset machine-learning methods further improve predictive power to a class separation in an equilibrated dataset of up to 83%. CONCLUSION: We present a computational method to automatically select and rank peptides for the stimulation of potentially protective or otherwise functionally altering antibodies. It can be shown that integration of variability, post-translational modification pattern conservation and B-cell antigenicity improve rational selection over random guessing. Probably more important, we find that for about 50% of antigen the approach works substantially better than for the overall dataset of 57 proteins. Essentially as a side effect our method optimizes for presumably best applicable peptides as they tend to be likely unmodified and as invariable as possible which is answering needs in diagnosis and treatment of pathogen infection. In addition we show the potential for further improvement by the application of machine-learning methods, in particular Random Forests.",2008 Jan 7,"['Sollner, Johannes', 'Grohmann, Rainer', 'Rapberger, Ronald', 'Perco, Paul', 'Lukas, Arno', 'Mayer, Bernd']",Immunome Res,,,True
98b07ff87d658b09a3284a78b88ebe5687475d5a,PMC,HLA class I supertypes: a revised and updated classification,http://dx.doi.org/10.1186/1471-2172-9-1,PMC2245908,18211710,CC BY,"BACKGROUND: Class I major histocompatibility complex (MHC) molecules bind, and present to T cells, short peptides derived from intracellular processing of proteins. The peptide repertoire of a specific molecule is to a large extent determined by the molecular structure accommodating so-called main anchor positions of the presented peptide. These receptors are extremely polymorphic, and much of the polymorphism influences the peptide-binding repertoire. However, despite this polymorphism, class I molecules can be clustered into sets of molecules that bind largely overlapping peptide repertoires. Almost a decade ago we introduced this concept of clustering human leukocyte antigen (HLA) alleles and defined nine different groups, denominated as supertypes, on the basis of their main anchor specificity. The utility of this original supertype classification, as well several other subsequent arrangements derived by others, has been demonstrated in a large number of epitope identification studies. RESULTS: Following our original approach, in the present report we provide an updated classification of HLA-A and -B class I alleles into supertypes. The present analysis incorporates the large amount of class I MHC binding data and sequence information that has become available in the last decade. As a result, over 80% of the 945 different HLA-A and -B alleles examined to date can be assigned to one of the original nine supertypes. A few alleles are expected to be associated with repertoires that overlap multiple supertypes. Interestingly, the current analysis did not identify any additional supertype specificities. CONCLUSION: As a result of this updated analysis, HLA supertype associations have been defined for over 750 different HLA-A and -B alleles. This information is expected to facilitate epitope identification and vaccine design studies, as well as investigations into disease association and correlates of immunity. In addition, the approach utilized has been made more transparent, allowing others to utilize the classification approach going forward.",2008 Jan 22,"['Sidney, John', 'Peters, Bjoern', 'Frahm, Nicole', 'Brander, Christian', 'Sette, Alessandro']",BMC Immunol,,,True
20d1c063410f32eb59b3f3063d506c4888c80bec,PMC,Role of receptor polymorphism and glycosylation in syncytium induction and host range variation of ecotropic mouse gammaretroviruses,http://dx.doi.org/10.1186/1742-4690-5-2,PMC2248597,18186934,CC BY,"BACKGROUND: We previously identified unusual variants of Moloney and Friend ecotropic mouse gammaretroviruses that have altered host range and are cytopathic in cells of the wild mouse species Mus dunni. Cytopathicity was attributed to different amino acid substitutions at the same critical env residue involved in receptor interaction: S82F in the Moloney variant Spl574, and S84A in the Friend mouse leukemia virus F-S MLV. Because M. dunni cells carry a variant CAT-1 cell surface virus receptor (dCAT-1), we examined the role of this receptor variant in cytopathicity and host range. RESULTS: We expressed dCAT-1 or mCAT-1 of NIH 3T3 origin in cells that are not normally infectible with ecotropic MLVs and evaluated the transfectants for susceptibility to virus infection and to virus-induced syncytium formation. The dCAT-1 transfectants, but not the mCAT-1 transfectants, were susceptible to virus-induced cytopathicity, and this cytopathic response was accompanied by the accumulation of unintegrated viral DNA. The dCAT-1 transfectants, however, did not also reproduce the relative resistance of M. dunni cells to Moloney MLV, and the mCAT-1 transfectants did not show the relative resistance of NIH 3T3 cells to Spl574. Western analysis, use of glycosylation inhibitors and mutagenesis to remove receptor glycosylation sites identified a possible role for cell-specific glycosylation in the modulation of virus entry. CONCLUSION: Virus entry and virus-induced syncytium formation using the CAT-1 receptor are mediated by a small number of critical amino acid residues in receptor and virus Env. Virus entry is modulated by glycosylation of cellular proteins, and this effect is cell and virus-specific.",2008 Jan 10,"['Yan, Yuhe', 'Jung, Yong T', 'Wu, Tiyun', 'Kozak, Christine A']",Retrovirology,,,True
63f04bb7051a4d43795615877a0a351ca5d79740,PMC,Establishing a nationwide emergency department-based syndromic surveillance system for better public health responses in Taiwan,http://dx.doi.org/10.1186/1471-2458-8-18,PMC2249581,18201388,CC BY,"BACKGROUND: With international concern over emerging infectious diseases (EID) and bioterrorist attacks, public health is being required to have early outbreak detection systems. A disease surveillance team was organized to establish a hospital emergency department-based syndromic surveillance system (ED-SSS) capable of automatically transmitting patient data electronically from the hospitals responsible for emergency care throughout the country to the Centers for Disease Control in Taiwan (Taiwan-CDC) starting March, 2004. This report describes the challenges and steps involved in developing ED-SSS and the timely information it provides to improve in public health decision-making. METHODS: Between June 2003 and March 2004, after comparing various surveillance systems used around the world and consulting with ED physicians, pediatricians and internal medicine physicians involved in infectious disease control, the Syndromic Surveillance Research Team in Taiwan worked with the Real-time Outbreak and Disease Surveillance (RODS) Laboratory at the University of Pittsburgh to create Taiwan's ED-SSS. The system was evaluated by analyzing daily electronic ED data received in real-time from the 189 hospitals participating in this system between April 1, 2004 and March 31, 2005. RESULTS: Taiwan's ED-SSS identified winter and summer spikes in two syndrome groups: influenza-like illnesses and respiratory syndrome illnesses, while total numbers of ED visits were significantly higher on weekends, national holidays and the days of Chinese lunar new year than weekdays (p < 0.001). It also identified increases in the upper, lower, and total gastrointestinal (GI) syndrome groups starting in November 2004 and two clear spikes in enterovirus-like infections coinciding with the two school semesters. Using ED-SSS for surveillance of influenza-like illnesses and enteroviruses-related infections has improved Taiwan's pandemic flu preparedness and disease control capabilities. CONCLUSION: Taiwan's ED-SSS represents the first nationwide real-time syndromic surveillance system ever established in Asia. The experiences reported herein can encourage other countries to develop their own surveillance systems. The system can be adapted to other cultural and language environments for better global surveillance of infectious diseases and international collaboration.",2008 Jan 18,"['Wu, Tsung-Shu Joseph', 'Shih, Fuh-Yuan Frank', 'Yen, Muh-Yong', 'Wu, Jiunn-Shyan Julian', 'Lu, Shiou-Wen', 'Chang, Kevin Chi-Ming', 'Hsiung, Chao', 'Chou, Jr-How', 'Chu, Yu-Tseng', 'Chang, Hang', 'Chiu, Chan-Hsien', 'Tsui, Fu-Chiang Richard', 'Wagner, Michael M', 'Su, Ih-Jen', 'King, Chwan-Chuen']",BMC Public Health,,,True
f89c1c613071fcb7fdb5d956e91a807b83456ea3,PMC,Effects of intranasal TNFα on granulocyte recruitment and activity in healthy subjects and patients with allergic rhinitis,http://dx.doi.org/10.1186/1465-9921-9-15,PMC2253533,18234086,CC BY,"BACKGROUND: TNFα may contribute to the pathophysiology of airway inflammation. For example, we have recently shown that nasal administration of TNFα produces late phase co-appearance of granulocyte and plasma exudation markers on the mucosal surface. The objective of the present study was to examine indices of granulocyte presence and activity in response to intranasal TNFα challenge. METHODS: Healthy subjects and patients with allergic rhinitis (examined out of season) were subjected to nasal challenge with TNFα (10 μg) in a sham-controlled and crossover design. Nasal lavages were carried out prior to and 24 hours post challenge. Nasal biopsies were obtained post challenge. Nasal lavage fluid levels of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were analyzed as indices of neutrophil and eosinophil activity. Moreover, IL-8 and α(2)-macroglobulin were analyzed as markers of pro-inflammatory cytokine production and plasma exudation. Nasal biopsy numbers of neutrophils and eosinophils were monitored. RESULTS: Nasal lavage fluid levels of MPO recorded 24 hours post TNFα challenge were increased in healthy subjects (p = 0.0081) and in patients with allergic rhinitis (p = 0.0081) (c.f. sham challenge). Similarly, α(2)-macroglobulin was increased in healthy subjects (p = 0.014) and in patients with allergic rhinitis (p = 0.0034). Lavage fluid levels of ECP and IL-8 were not affected by TNFα challenge. TNFα increased the numbers of subepithelial neutrophils (p = 0.0021), but not the numbers of eosinophils. CONCLUSION: TNFα produces a nasal inflammatory response in humans that is characterised by late phase (i.e., 24 hours post challenge) neutrophil activity and plasma exudation.",2008 Jan 30,"['Widegren, Henrik', 'Erjefält, Jonas', 'Korsgren, Magnus', 'Andersson, Morgan', 'Greiff, Lennart']",Respir Res,,,True
06795e24716acde6e56c25d7845c92a97fa0268c,PMC,Viral genome sequencing by random priming methods,http://dx.doi.org/10.1186/1471-2164-9-5,PMC2254600,18179705,CC BY,"BACKGROUND: Most emerging health threats are of zoonotic origin. For the overwhelming majority, their causative agents are RNA viruses which include but are not limited to HIV, Influenza, SARS, Ebola, Dengue, and Hantavirus. Of increasing importance therefore is a better understanding of global viral diversity to enable better surveillance and prediction of pandemic threats; this will require rapid and flexible methods for complete viral genome sequencing. RESULTS: We have adapted the SISPA methodology [1-3] to genome sequencing of RNA and DNA viruses. We have demonstrated the utility of the method on various types and sources of viruses, obtaining near complete genome sequence of viruses ranging in size from 3,000–15,000 kb with a median depth of coverage of 14.33. We used this technique to generate full viral genome sequence in the presence of host contaminants, using viral preparations from cell culture supernatant, allantoic fluid and fecal matter. CONCLUSION: The method described is of great utility in generating whole genome assemblies for viruses with little or no available sequence information, viruses from greatly divergent families, previously uncharacterized viruses, or to more fully describe mixed viral infections.",2008 Jan 7,"['Djikeng, Appolinaire', 'Halpin, Rebecca', 'Kuzmickas, Ryan', 'DePasse, Jay', 'Feldblyum, Jeremy', 'Sengamalay, Naomi', 'Afonso, Claudio', 'Zhang, Xinsheng', 'Anderson, Norman G', 'Ghedin, Elodie', 'Spiro, David J']",BMC Genomics,,,True
308e91d0c4575362a0d169b9ed31c60f79a86437,PMC,Tear lipocalin is the major endonuclease in tears,,PMC2254967,18334931,CC BY,"PURPOSE: Human endonucleases are integral to apoptosis in which unwanted or potentially harmful cells are eliminated. The rapid turnover of ocular surface epithelium and microbial colonization of the eyelids are continual sources of DNA in tears. Here, we determine the principal sources of endonuclease activity in tears. METHODS: Endonucleases in human tears were identified after Sephadex G100 gel filtration. DNA hydrolyzing activity was measured by the conversion pUC19 plasmid DNA to its circular form in agarose gels. Fractions with endonuclease activity were further isolated using a combination ConA-Sepharose DNA, oligo (dT) cellulose, and anion exchange chromatographies. The molecular weights of the DNA hydrolyzing proteins were estimated in zymograms and by calibration of size exclusion chromatography. DNase activities were characterized for activity at a variety of pH and ion concentrations as well as in the presence of inhibitors including NiCl(2), ZnCl(2), G-actin, and aurintricarboxylic acid (ATA). To determine the mode of hydrolysis, the cleaved ends of the DNA digested by tear DNases were analyzed by 3′ and 5′ end labeling using either terminal deoxynucleotidyl transferase or polynucleotide kinase with or without pretreatment with alkaline phosphatase. RESULTS: Tear lipocalin (TL) accounts for over 75% of the DNA catalytic activity in tears while a second endonuclease, ~34 kDa, is responsible for less than 24% of the activity. Both are Mg(2+) dependent enzyme endonucleases that are enhanced by Ca(2+), active at physiologic pH, inhibited by aurintricarboxylic acid, and catalyze hydrolysis of DNA to produce 3′-OH/5′P ends. However, the two enzymes can be distinguished by the inhibitory effect of NiCl(2) and the sizes of the cleaved DNA fragments. CONCLUSIONS: Two magnesium dependent extracellular endonucleases were identified in tears that are different from other major human extracellular nucleases. TL is the principal endonuclease in human tear fluid. Tear endonucleases have unique characteristics that differ from other known human endonucleases.",2008 Jan 29,"['Yusifov, Taleh N.', 'Abduragimov, Adil R.', 'Narsinh, Kiran', 'Gasymov, Oktay K.', 'Glasgow, Ben J.']",Mol Vis,,,True
eb4b8f43f68db5e493984b7e4e56d9f804d7e885,PMC,Can the concept of Health Promoting Schools help to improve students' health knowledge and practices to combat the challenge of communicable diseases: Case study in Hong Kong?,http://dx.doi.org/10.1186/1471-2458-8-42,PMC2258284,18234083,CC BY,"BACKGROUND: The growing epidemics of emerging infectious diseases has raised the importance of a setting approach and include the Health Promoting School (HPS) framework to promote better health and hygiene. Built on the concept of 'the' HPS framework, the Hong Kong Healthy Schools Award scheme includes ""Personal Health Skills"" as one of its key aspects to improve student hygiene knowledge and practices. This study examines the differences in student perceptions, knowledge and health behaviours between those schools that have adopted the HPS framework and those that have not adopted. METHODS: A cross-sectional study using multi-stage random sampling was conducted among schools with awards (HSA) and those schools not involved in the award scheme nor adopting the concept of HPS (non-HPS). For HSA group, 5 primary schools and 7 secondary schools entered the study with 510 students and 789 students sampled respectively. For the 'Non-HPS' group, 8 primary schools and 7 secondary schools entered the study with 676 students and 725 students sampled respectively. A self-administered questionnaire was used as the measuring instrument. RESULTS: Students in the HSA category were found to be better with statistical significance in personal hygiene practice, knowledge on health and hygiene, as well as access to health information. HSA schools were reported to have better school health policy, higher degrees of community participation, and better hygienic environment. CONCLUSION: Students in schools that had adopted the HPS framework had a more positive health behaviour profile than those in non-HPS schools. Although a causal relationship is yet to be established, the HPS appears to be a viable approach for addressing communicable diseases.",2008 Jan 30,"['Lee, Albert', 'Wong, Martin CS', 'Keung, Vera MW', 'Yuen, Hilda SK', 'Cheng, Frances', 'Mok, Jennifer SY']",BMC Public Health,,,True
d77dcb77a4a620fd1de81f309bff0e04e2578272,PMC,Hotspot Hunter: a computational system for large-scale screening and selection of candidate immunological hotspots in pathogen proteomes,http://dx.doi.org/10.1186/1471-2105-9-S1-S19,PMC2259420,18315850,CC BY,"BACKGROUND: T-cell epitopes that promiscuously bind to multiple alleles of a human leukocyte antigen (HLA) supertype are prime targets for development of vaccines and immunotherapies because they are relevant to a large proportion of the human population. The presence of clusters of promiscuous T-cell epitopes, immunological hotspots, has been observed in several antigens. These clusters may be exploited to facilitate the development of epitope-based vaccines by selecting a small number of hotspots that can elicit all of the required T-cell activation functions. Given the large size of pathogen proteomes, including of variant strains, computational tools are necessary for automated screening and selection of immunological hotspots. RESULTS: Hotspot Hunter is a web-based computational system for large-scale screening and selection of candidate immunological hotspots in pathogen proteomes through analysis of antigenic diversity. It allows screening and selection of hotspots specific to four common HLA supertypes, namely HLA class I A2, A3, B7 and class II DR. The system uses Artificial Neural Network and Support Vector Machine methods as predictive engines. Soft computing principles were employed to integrate the prediction results produced by both methods for robust prediction performance. Experimental validation of the predictions showed that Hotspot Hunter can successfully identify majority of the real hotspots. Users can predict hotspots from a single protein sequence, or from a set of aligned protein sequences representing pathogen proteome. The latter feature provides a global view of the localizations of the hotspots in the proteome set, enabling analysis of antigenic diversity and shift of hotspots across protein variants. The system also allows the integration of prediction results of the four supertypes for identification of hotspots common across multiple supertypes. The target selection feature of the system shortlists candidate peptide hotspots for the formulation of an epitope-based vaccine that could be effective against multiple variants of the pathogen and applicable to a large proportion of the human population. CONCLUSION: Hotspot Hunter is publicly accessible at . It is a new generation computational tool aiding in epitope-based vaccine design.",2008 Feb 13,"['Zhang, Guang Lan', 'Khan, Asif M', 'Srinivasan, Kellathur N', 'Heiny, AT', 'Lee, KX', 'Kwoh, Chee Keong', 'August, J Thomas', 'Brusic, Vladimir']",BMC Bioinformatics,,,True
111968f7fb102882c193488965e41d5d0f0103dc,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,True
40a9af5b24845df11d024ef657f7c91ffd6871f4,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
02f6c1a9ceadd3a52df836f08c84f0c37d01fc92,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
f27cd7dcbc541ade60e624d3b8a01271b8bc0994,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
3780a3ec4d25889c7a447b1c664d4c35e5031b0d,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
7a3ae584544d0a1c7bf4fd406dd23216e30e45e8,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
94958f7e5269bf74f113e80e2ec1b26a95a44d50,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
279ac6b430bb584496e226d0ae4bb19aace9bcff,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
70b0b8c7e82529cbdf874ec2932446edff21aa74,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
153dc20c0306ef3ec12ea5d4316b63d8ddc78ca1,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
cb00f85d57af6c0f4b1e24f81e121641f53715a5,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
0dd0ea8ef4cd2637dff19c517d7b0f21b323c0c8,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
e11481664a0ba85ec7117fa32f147c10681065ef,PMC,Comparative phyloinformatics of virus genes at micro and macro levels in a distributed computing environment,http://dx.doi.org/10.1186/1471-2105-9-S1-S23,PMC2259424,18315855,CC BY,"BACKGROUND: Preparedness for a possible global pandemic caused by viruses such as the highly pathogenic influenza A subtype H5N1 has become a global priority. In particular, it is critical to monitor the appearance of any new emerging subtypes. Comparative phyloinformatics can be used to monitor, analyze, and possibly predict the evolution of viruses. However, in order to utilize the full functionality of available analysis packages for large-scale phyloinformatics studies, a team of computer scientists, biostatisticians and virologists is needed – a requirement which cannot be fulfilled in many cases. Furthermore, the time complexities of many algorithms involved leads to prohibitive runtimes on sequential computer platforms. This has so far hindered the use of comparative phyloinformatics as a commonly applied tool in this area. RESULTS: In this paper the graphical-oriented workflow design system called Quascade and its efficient usage for comparative phyloinformatics are presented. In particular, we focus on how this task can be effectively performed in a distributed computing environment. As a proof of concept, the designed workflows are used for the phylogenetic analysis of neuraminidase of H5N1 isolates (micro level) and influenza viruses (macro level). The results of this paper are hence twofold. Firstly, this paper demonstrates the usefulness of a graphical user interface system to design and execute complex distributed workflows for large-scale phyloinformatics studies of virus genes. Secondly, the analysis of neuraminidase on different levels of complexity provides valuable insights of this virus's tendency for geographical based clustering in the phylogenetic tree and also shows the importance of glycan sites in its molecular evolution. CONCLUSION: The current study demonstrates the efficiency and utility of workflow systems providing a biologist friendly approach to complex biological dataset analysis using high performance computing. In particular, the utility of the platform Quascade for deploying distributed and parallelized versions of a variety of computationally intensive phylogenetic algorithms has been shown. Secondly, the analysis of the utilized H5N1 neuraminidase datasets at macro and micro levels has clearly indicated a pattern of spatial clustering of the H5N1 viral isolates based on geographical distribution rather than temporal or host range based clustering.",2008 Feb 13,"['Singh, Dadabhai T', 'Trehan, Rahul', 'Schmidt, Bertil', 'Bretschneider, Timo']",BMC Bioinformatics,,,False
db5b99eac0c11848467c40af5744442e0b869870,PMC,Universal primers that amplify RNA from all three flavivirus subgroups,http://dx.doi.org/10.1186/1743-422X-5-16,PMC2263041,18218114,CC BY,"BACKGROUND: Species within the Flavivirus genus pose public health problems around the world. Increasing cases of Dengue and Japanese encephalitis virus in Asia, frequent outbreaks of Yellow fever virus in Africa and South America, and the ongoing spread of West Nile virus throughout the Americas, show the geographical burden of flavivirus diseases. Flavivirus infections are often indistinct from and confused with other febrile illnesses. Here we review the specificity of published primers, and describe a new universal primer pair that can detect a wide range of flaviviruses, including viruses from each of the recognised subgroups. RESULTS: Bioinformatic analysis of 257 published full-length Flavivirus genomes revealed conserved regions not previously targeted by primers. Two degenerate primers, Flav100F and Flav200R were designed from these regions and used to generate an 800 base pair cDNA product. The region amplified encoded part of the methyltransferase and most of the RNA-dependent-RNA-polymerase (NS5) coding sequence. One-step RT-PCR testing was successful using standard conditions with RNA from over 60 different flavivirus strains representing about 50 species. The cDNA from each virus isolate was sequenced then used in phylogenetic analyses and database searches to confirm the identity of the template RNA. CONCLUSION: Comprehensive testing has revealed the broad specificity of these primers. We briefly discuss the advantages and uses of these universal primers.",2008 Jan 24,"['Maher-Sturgess, Sheryl L', 'Forrester, Naomi L', 'Wayper, Paul J', 'Gould, Ernest A', 'Hall, Roy A', 'Barnard, Ross T', 'Gibbs, Mark J']",Virol J,,,True
aae7699e079d2964df8078931cd0f94d4b1423d9,PMC,Amino Acid Similarity Accounts for T Cell Cross-Reactivity and for “Holes” in the T Cell Repertoire,http://dx.doi.org/10.1371/journal.pone.0001831,PMC2263130,18350167,CC0,"BACKGROUND: Cytotoxic T cell (CTL) cross-reactivity is believed to play a pivotal role in generating immune responses but the extent and mechanisms of CTL cross-reactivity remain largely unknown. Several studies suggest that CTL clones can recognize highly diverse peptides, some sharing no obvious sequence identity. The emerging realization in the field is that T cell receptors (TcR) recognize multiple distinct ligands. PRINCIPAL FINDINGS: First, we analyzed peptide scans of the HIV epitope SLFNTVATL (SFL9) and found that TCR specificity is position dependent and that biochemically similar amino acid substitutions do not drastically affect recognition. Inspired by this, we developed a general model of TCR peptide recognition using amino acid similarity matrices and found that such a model was able to predict the cross-reactivity of a diverse set of CTL epitopes. With this model, we were able to demonstrate that seemingly distinct T cell epitopes, i.e., ones with low sequence identity, are in fact more biochemically similar than expected. Additionally, an analysis of HIV immunogenicity data with our model showed that CTLs have the tendency to respond mostly to peptides that do not resemble self-antigens. CONCLUSIONS: T cell cross-reactivity can thus, to an extent greater than earlier appreciated, be explained by amino acid similarity. The results presented in this paper will help resolving some of the long-lasting discussions in the field of T cell cross-reactivity.",2008 Mar 19,"['Frankild, Sune', 'de Boer, Rob J.', 'Lund, Ole', 'Nielsen, Morten', 'Kesmir, Can']",PLoS One,,,True
15372a2da42ddcb56ac4edc88090a6a425c5fad0,PMC,The cost of community-managed viral respiratory illnesses in a cohort of healthy preschool-aged children,http://dx.doi.org/10.1186/1465-9921-9-11,PMC2266731,18215329,CC BY,"BACKGROUND: Acute respiratory illnesses (ARIs) during childhood are often caused by respiratory viruses, result in significant morbidity, and have associated costs for families and society. Despite their ubiquity, there is a lack of interdisciplinary epidemiologic and economic research that has collected primary impact data, particularly associated with indirect costs, from families during ARIs in children. METHODS: We conducted a 12-month cohort study in 234 preschool children with impact diary recording and PCR testing of nose-throat swabs for viruses during an ARI. We used applied values to estimate a virus-specific mean cost of ARIs. RESULTS: Impact diaries were available for 72% (523/725) of community-managed illnesses between January 2003 and January 2004. The mean cost of ARIs was AU$309 (95% confidence interval $263 to $354). Influenza illnesses had a mean cost of $904, compared with RSV, $304, the next most expensive single-virus illness, although confidence intervals overlapped. Mean carer time away from usual activity per day was two hours for influenza ARIs and between 30 and 45 minutes for all other ARI categories. CONCLUSION: From a societal perspective, community-managed ARIs are a significant cost burden on families and society. The point estimate of the mean cost of community-managed influenza illnesses in healthy preschool aged children is three times greater than those illnesses caused by RSV and other respiratory viruses. Indirect costs, particularly carer time away from usual activity, are the key cost drivers for ARIs in children. The use of parent-collected specimens may enhance ARI surveillance and reduce any potential Hawthorne effect caused by compliance with study procedures. These findings reinforce the need for further integrated epidemiologic and economic research of ARIs in children to allow for comprehensive cost-effectiveness assessments of preventive and therapeutic options.",2008 Jan 24,"['Lambert, Stephen B', 'Allen, Kelly M', 'Carter, Robert C', 'Nolan, Terence M']",Respir Res,,,True
ab54f13666ed771c15684d73ff6bcc7c92b8ae05,PMC,Validity of the Common Cold Questionnaire (CCQ) in Asthma Exacerbations,http://dx.doi.org/10.1371/journal.pone.0001802,PMC2266793,18350141,CC BY,"BACKGROUND: The common cold questionnaire (CCQ) is used to discriminate those with and without a viral infection. Its usefulness in people with acute asthma is unknown. Our aim was to assess the ability of the CCQ to detect viral infection and to monitor recovery during a viral induced asthma exacerbation and confirmed by virological testing. METHODOLOGY/PRINCIPAL FINDINGS: We studied subjects (≥7 yrs) admitted to hospital with acute asthma and diagnosed as positive (n = 63), or negative to viral infection (n = 27) according to molecular and virological testing from respiratory samples. CCQ, asthma history and asthma control questionnaires were completed and repeated 4–6 weeks later. Sensitivity, specificity, and response to change of the CCQ were assessed by receiver operator curve (ROC) analysis and effect size calculation respectively. The CCQ did not discriminate between viral and non-viral infection for subjects with asthma (sensitivity = 76.2%; specificity = 29.6%). ROC analysis could not differentiate between positive or negative virus in subjects with asthma. The CCQ had a large response to change following recovery (effect size = 1.01). 39% of subjects recovering from viral exacerbation remained positive to virological testing at follow-up despite improvement in clinical symptoms. The CCQ reflected clinical improvement in these subjects, thus providing additional information to complement virological testing. CONCLUSIONS/SIGNIFICANCE: The CCQ is a useful instrument for monitoring response to viral infection in people with asthma. Reliable differentiation between viral and non-viral asthma exacerbations was not achieved with the CCQ and requires specific virological testing. When combined with virological testing, the CCQ should be a useful outcome measure for evaluating therapies in viral-induced asthma.",2008 Mar 19,"['Powell, Heather', 'Smart, Joanne', 'Wood, Lisa G.', 'Grissell, Terry', 'Shafren, Darren R.', 'Hensley, Michael J.', 'Gibson, Peter G.']",PLoS One,,,True
e6f54fcf3460165fb558903e975a526bc98e4eba,PMC,A Virus-Encoded Cell–Cell Fusion Machine Dependent on Surrogate Adhesins,http://dx.doi.org/10.1371/journal.ppat.1000016,PMC2267009,18369467,CC BY,"The reovirus fusion-associated small transmembrane (FAST) proteins function as virus-encoded cellular fusogens, mediating efficient cell–cell rather than virus–cell membrane fusion. With ectodomains of only ∼20–40 residues, it is unclear how such diminutive viral fusion proteins mediate the initial stages (i.e. membrane contact and close membrane apposition) of the fusion reaction that precede actual membrane merger. We now show that the FAST proteins lack specific receptor-binding activity, and in their natural biological context of promoting cell–cell fusion, rely on cadherins to promote close membrane apposition. The FAST proteins, however, are not specifically reliant on cadherin engagement to mediate membrane apposition as indicated by their ability to efficiently utilize other adhesins in the fusion reaction. Results further indicate that surrogate adhesion proteins that bridge membranes as close as 13 nm apart enhance FAST protein-induced cell–cell fusion, but active actin remodelling is required for maximal fusion activity. The FAST proteins are the first example of membrane fusion proteins that have specifically evolved to function as opportunistic fusogens, designed to exploit and convert naturally occurring adhesion sites into fusion sites. The capacity of surrogate, non-cognate adhesins and active actin remodelling to enhance the cell–cell fusion activity of the FAST proteins are features perfectly suited to the structural and functional evolution of these fusogens as the minimal fusion component of a virus-encoded cellular fusion machine. These results also provide a basis for reconciling the rudimentary structure of the FAST proteins with their capacity to fuse cellular membranes.",2008 Mar 7,"['Salsman, Jayme', 'Top, Deniz', 'Barry, Christopher', 'Duncan, Roy']",PLoS Pathog,,,True
3f7c34653f6fcd0675f13b47461b74cd0f0a51fd,PMC,Membrane interaction and structure of the transmembrane domain of influenza hemagglutinin and its fusion peptide complex,http://dx.doi.org/10.1186/1741-7007-6-2,PMC2267159,18197965,CC BY,"BACKGROUND: To study the organization and interaction with the fusion domain (or fusion peptide, FP) of the transmembrane domain (TMD) of influenza virus envelope glycoprotein for its role in membrane fusion which is also essential in the cellular trafficking of biomolecules and sperm-egg fusion. RESULTS: The fluorescence and gel electrophoresis experiments revealed a tight self-assembly of TMD in the model membrane. A weak but non-random interaction between TMD and FP in the membrane was found. In the complex, the central TMD oligomer was packed by FP in an antiparallel fashion. FP insertion into the membrane was altered by binding to TMD. An infrared study exhibited an enhanced membrane perturbation by the complex formation. A model was built to illustrate the role of TMD in the late stages of influenza virus-mediated membrane fusion reaction. CONCLUSION: The TMD oligomer anchors the fusion protein in the membrane with minimal destabilization to the membrane. Upon associating with FP, the complex exerts a synergistic effect on the membrane perturbation. This effect is likely to contribute to the complete membrane fusion during the late phase of fusion protein-induced fusion cascade. The results presented in the work characterize the nature of the interaction of TMD with the membrane and TMD in a complex with FP in the steps leading to pore initiation and dilation during virus-induced fusion. Our data and proposed fusion model highlight the key role of TMD-FP interaction and have implications on the fusion reaction mediated by other type I viral fusion proteins. Understanding the molecular mechanism of membrane fusion may assist in the design of anti-viral drugs.",2008 Jan 15,"['Chang, Ding-Kwo', 'Cheng, Shu-Fang', 'Kantchev, Eric Aseen B', 'Lin, Chi-Hui', 'Liu, Yu-Tsan']",BMC Biol,,,True
00acd3fd31ed0cde8df286697caefc5298e54df1,PMC,"Distinguishing Molecular Features and Clinical Characteristics of a Putative New Rhinovirus Species, Human Rhinovirus C (HRV C)",http://dx.doi.org/10.1371/journal.pone.0001847,PMC2268738,18382652,CC BY,"BACKGROUND: Human rhinoviruses (HRVs) are the most frequently detected pathogens in acute respiratory tract infections (ARTIs) and yet little is known about the prevalence, recurrence, structure and clinical impact of individual members. During 2007, the complete coding sequences of six previously unknown and highly divergent HRV strains were reported. To catalogue the molecular and clinical features distinguishing the divergent HRV strains, we undertook, for the first time, in silico analyses of all available polyprotein sequences and performed retrospective reviews of the medical records of cases in which variants of the prototype strain, HRV-QPM, had been detected. METHODOLOGY/PRINCIPLE FINDINGS: Genomic analyses revealed that the six divergent strains, residing within a clade we previously called HRV A2, had the shortest polyprotein of all picornaviruses investigated. Structure-based amino acid alignments identified conserved motifs shared among members of the genus Rhinovirus as well as substantive deletions and insertions unique to the divergent strains. Deletions mostly affected regions encoding proteins traditionally involved in antigenicity and serving as HRV and HEV receptor footprints. Because the HRV A2 strains cannot yet be cultured, we created homology models of predicted HRV-QPM structural proteins. In silico comparisons confirmed that HRV-QPM was most closely related to the major group HRVs. HRV-QPM was most frequently detected in infants with expiratory wheezing or persistent cough who had been admitted to hospital and required supplemental oxygen. It was the only virus detected in 65% of positive individuals. These observations contributed to an objective clinical impact ranging from mild to severe. CONCLUSIONS: The divergent strains did not meet classification requirements for any existing species of the genus Rhinovirus or Enterovirus. HRV A2 strains should be partitioned into at least one new species, putatively called Human rhinovirus C, populated by members detected with high frequency, from individuals with respiratory symptoms requiring hospital admission.",2008 Apr 2,"['McErlean, Peter', 'Shackelton, Laura A.', 'Andrews, Emily', 'Webster, Dale R.', 'Lambert, Stephen B.', 'Nissen, Michael D.', 'Sloots, Theo P.', 'Mackay, Ian M.']",PLoS One,,,True
808dfc4c59f3e2e9150aa5542ea227718741388b,PMC,Towards a Coronavirus-Based HIV Multigene Vaccine,http://dx.doi.org/10.1080/17402520600579168,PMC2270750,17162377,CC BY,"Human immunodeficiency virus (HIV) infection represents one of the major health threats in the developing world. The costly treatment of infected individuals with multiple highly efficient anti-HIV drugs is only affordable in industrialized countries. Thus, an efficient vaccination strategy is required to prevent the further spread of the infection. The molecular biology of coronaviruses and particular features of the human coronavirus 229E (HCoV 229E) indicate that HCoV 229E-based vaccine vectors can become a new class of highly efficient vaccines. First, the receptor of HCoV 229E, human aminopeptidase N (hAPN or CD13) is expressed mainly on human dendritic cells (DCs) and macrophages indicating that targeting of HCoV 229E-based vectors to professional antigen presenting cells can be achieved by receptor-mediated transduction. Second, HCoV 229E structural genes can be replaced by multiple transcriptional units encoding various antigens. These virus-like particles (VLPs) containing HCoV 229E-based vector RNA have the ability to transduce human DCs and to mediate heterologous gene expression in these cells. Finally, coronavirus infections are associated with mainly respiratory and enteric diseases, and natural transmission of coronaviruses occurs via mucosal surfaces. In humans, HCoV 229E causes common cold by infecting the upper respiratory tract. HCoV 229E infections are mainly encountered in children and re-infection occurs frequently in adults. It is thus most likely that pre-existing immunity against HCoV 229E will not significantly impact on the vaccination efficiency if HCoV 229E-based vectors are used in humans.",2006 Jun-Dec,"['Eriksson, Klara K.', 'Makia, Divine', 'Maier, Reinhard', 'Ludewig, Burkhard', 'Thiel, Volker']",Clin Dev Immunol,,,True
5e2457559eab2f9b131de9084d5dfc66bd875aee,PMC,Identification of a contemporary human parechovirus type 1 by VIDISCA and characterisation of its full genome,http://dx.doi.org/10.1186/1743-422X-5-26,PMC2270820,18269761,CC BY,"BACKGROUND: Enteritis is caused by a spectrum of viruses that is most likely not fully characterised. When testing stool samples by cell culture, virus isolates are sometimes obtained which cannot be typed by current methods. In this study we used VIDISCA, a virus identification method which has not yet been widely applied, on such an untyped virus isolate. RESULTS: We found a human parechovirus (HPeV) type 1 (strain designation: BNI-788st). Because genomes of contemporary HPeV1 were not available, we determined its complete genome sequence. We found that the novel strain was likely the result of recombination between structural protein genes of an ancestor of contemporary HPeV1 strains and nonstructural protein genes from an unknown ancestor, most closely related to HPeV3. In contrast to the non-structural protein genes of other HPeV prototype strains, the non-structural protein genes of BNI-788st and HPeV3 prototype strains did not co-segregate in bootscan analysis with that of other prototype strains. CONCLUSION: HPeV3 nonstructural protein genes may form a distinct element in a pool of circulating HPeV non-structural protein genes. More research into the complex HPeV evolution is required to connect virus ecology with disease patterns in humans.",2008 Feb 12,"['de Souza Luna, Luciano Kleber', 'Baumgarte, Sigrid', 'Grywna, Klaus', 'Panning, Marcus', 'Drexler, Jan Felix', 'Drosten, Christian']",Virol J,,,True
eb4e468f68974db552de7a9f4e41d95607b0c461,PMC,"Genomic organization, sequence divergence, and recombination of feline immunodeficiency virus from lions in the wild",http://dx.doi.org/10.1186/1471-2164-9-66,PMC2270836,18251995,CC BY,"BACKGROUND: Feline immunodeficiency virus (FIV) naturally infects multiple species of cat and is related to human immunodeficiency virus in humans. FIV infection causes AIDS-like disease and mortality in the domestic cat (Felis catus) and serves as a natural model for HIV infection in humans. In African lions (Panthera leo) and other exotic felid species, disease etiology introduced by FIV infection are less clear, but recent studies indicate that FIV causes moderate to severe CD4 depletion. RESULTS: In this study, comparative genomic methods are used to evaluate the full proviral genome of two geographically distinct FIV subtypes isolated from free-ranging lions. Genome organization of FIV(Ple )subtype B (9891 bp) from lions in the Serengeti National Park in Tanzania and FIV(Ple )subtype E (9899 bp) isolated from lions in the Okavango Delta in Botswana, both resemble FIV genome sequence from puma, Pallas cat and domestic cat across 5' LTR, gag, pol, vif, orfA, env, rev and 3'LTR regions. Comparative analyses of available full-length FIV consisting of subtypes A, B and C from FIV(Fca), Pallas cat FIV(Oma )and two puma FIV(Pco )subtypes A and B recapitulate the species-specific monophyly of FIV marked by high levels of genetic diversity both within and between species. Across all FIV(Ple )gene regions except env, lion subtypes B and E are monophyletic, and marginally more similar to Pallas cat FIV(Oma )than to other FIV. Sequence analyses indicate the SU and TM regions of env vary substantially between subtypes, with FIV(Ple )subtype E more related to domestic cat FIV(Fca )than to FIV(Ple) subtype B and FIV(Oma )likely reflecting recombination between strains in the wild. CONCLUSION: This study demonstrates the necessity of whole-genome analysis to complement population/gene-based studies, which are of limited utility in uncovering complex events such as recombination that may lead to functional differences in virulence and pathogenicity. These full-length lion lentiviruses are integral to the advancement of comparative genomics of human pathogens, as well as emerging disease in wild populations of endangered species.",2008 Feb 5,"['Pecon-Slattery, Jill', 'McCracken, Carrie L', 'Troyer, Jennifer L', 'VandeWoude, Sue', 'Roelke, Melody', 'Sondgeroth, Kerry', 'Winterbach, Christiaan', 'Winterbach, Hanlie', ""O'Brien, Stephen J""]",BMC Genomics,,,True
aa34a2ba35c3daf0b882dfa8b96e65aa251b5ea8,PMC,Epigrass: a tool to study disease spread in complex networks,http://dx.doi.org/10.1186/1751-0473-3-3,PMC2275240,18302744,CC BY,"BACKGROUND: The construction of complex spatial simulation models such as those used in network epidemiology, is a daunting task due to the large amount of data involved in their parameterization. Such data, which frequently resides on large geo-referenced databases, has to be processed and assigned to the various components of the model. All this just to construct the model, then it still has to be simulated and analyzed under different epidemiological scenarios. This workflow can only be achieved efficiently by computational tools that can automate most, if not all, these time-consuming tasks. In this paper, we present a simulation software, Epigrass, aimed to help designing and simulating network-epidemic models with any kind of node behavior. RESULTS: A Network epidemiological model representing the spread of a directly transmitted disease through a bus-transportation network connecting mid-size cities in Brazil. Results show that the topological context of the starting point of the epidemic is of great importance from both control and preventive perspectives. CONCLUSION: Epigrass is shown to facilitate greatly the construction, simulation and analysis of complex network models. The output of model results in standard GIS file formats facilitate the post-processing and analysis of results by means of sophisticated GIS software.",2008 Feb 26,"['Coelho, Flávio C', 'Cruz, Oswaldo G', 'Codeço, Cláudia T']",Source Code Biol Med,,,True
66f425e847bc112e32f81cac4c2c57b1b6d0f284,PMC,Autoimmune Cholangitis in the SJL/J Mouse is Antigen Non-specific,http://dx.doi.org/10.1080/1044667021000096455,PMC2276095,12739787,CC BY,"Primary biliary cirrhosis (PBC) is an autoimmune disease characterized by intrahepatic bile duct destruction and the production of anti-mitochondrial antibodies (AMA). The absence of an animal model has been a striking impedance in defining the molecular basis of disease. Previous work has suggested that SJL/J mice immunize with the pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial autoantigen of PBC, leads to the development of lymphoid cell infiltration in portal tracts and a model system coined autoimmune cholangitis. We hypothesized that this pathology would be augmented if immunization occurred in the presence of IFN-γ injections. Accordingly, SJL/J mice were immunized with PDC-E2 and, for purpose of control, α-casein. Subgroups of mice were also treated with exogenous IFN-γ. As expected, mice immunized with PDC-E2, with or without IFN-γ, developed high titer AMAs. In contrast, mice immunized with α-casein, develop antinuclear antibodies. More importantly, the livers from mice immunized with PDC-E2 and/or those immunized with α-casein all displayed lymphoid cell infiltration to the portal tracts, irrespective of bile duct size. Indeed, there was no significant difference between the experimental and the control groups by histologic analysis. Thus, autoimmune cholangitis in these mice is antigen non-specific.",2002 Jun,"['Sasaki, Motoko', 'Allina, Jorge', 'Odin, Joseph A.', 'Thung, Swan N.', 'Coppel, Ross', 'Nakanuma, Yasuni', 'Gershwin, M. Eric']",Dev Immunol,,,True
060201d43460ac305a26ac4b0acca66cd41c151a,PMC,The Search for a Practical Approach to Emerging Diseases: The Case of Severe Acute Respiratory Syndrome (SARS),http://dx.doi.org/10.1080/1044667031000137575,PMC2276106,12885151,CC BY,"The plague, which the Board of Health had feared might enter with the German troops into the Milanese, had entered it indeed, as is well known; and it is likewise well known, that it paused not here, but invaded and ravaged a great part of Italy. (A. Manzoni, The Bethrothed, 1826)",2002 Sep,"['Selmi, Carlo', 'Ansari, Aftab A.', 'Invernizzi, Pietro', 'Podda, Mauro', 'Gershwin, M. Eric']",Dev Immunol,,,True
050e73f86cfa4ab3f3fc84b0cb55ac779fb9abc2,PMC,"La Crosse virus infectivity, pathogenesis, and immunogenicity in mice and monkeys",http://dx.doi.org/10.1186/1743-422X-5-25,PMC2276200,18267012,CC BY,"BACKGROUND: La Crosse virus (LACV), family Bunyaviridae, was first identified as a human pathogen in 1960 after its isolation from a 4 year-old girl with fatal encephalitis in La Crosse, Wisconsin. LACV is a major cause of pediatric encephalitis in North America and infects up to 300,000 persons each year of which 70–130 result in severe disease of the central nervous system (CNS). As an initial step in the establishment of useful animal models to support vaccine development, we examined LACV infectivity, pathogenesis, and immunogenicity in both weanling mice and rhesus monkeys. RESULTS: Following intraperitoneal inoculation of mice, LACV replicated in various organs before reaching the CNS where it replicates to high titer causing death from neurological disease. The peripheral site where LACV replicates to highest titer is the nasal turbinates, and, presumably, LACV can enter the CNS via the olfactory neurons from nasal olfactory epithelium. The mouse infectious dose(50 )and lethal dose(50 )was similar for LACV administered either intranasally or intraperitoneally. LACV was highly infectious for rhesus monkeys and infected 100% of the animals at 10 PFU. However, the infection was asymptomatic, and the monkeys developed a strong neutralizing antibody response. CONCLUSION: In mice, LACV likely gains access to the CNS via the blood stream or via olfactory neurons. The ability to efficiently infect mice intranasally raises the possibility that LACV might use this route to infect its natural hosts. Rhesus monkeys are susceptible to LACV infection and develop strong neutralizing antibody responses after inoculation with as little as 10 PFU. Mice and rhesus monkeys are useful animal models for LACV vaccine immunologic testing although the rhesus monkey model is not optimal.",2008 Feb 11,"['Bennett, Richard S', 'Cress, Christina M', 'Ward, Jerrold M', 'Firestone, Cai-Yen', 'Murphy, Brian R', 'Whitehead, Stephen S']",Virol J,,,True
3370214f4f7242b2a6ef23df718ef0f8b863a04c,PMC,Transmission Pathways of Foot-and-Mouth Disease Virus in the United Kingdom in 2007,http://dx.doi.org/10.1371/journal.ppat.1000050,PMC2277462,18421380,CC BY,"Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols). Here, we show that the outbreaks of FMD in the United Kingdom in August 2007 were caused by a derivative of FMDV O(1) BFS 1860, a virus strain handled at two FMD laboratories located on a single site at Pirbright in Surrey. Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August. Complete genome sequence analysis of FMD viruses conducted in real-time have identified the initial and intermediate sources of these outbreaks and demonstrate the value of such techniques in providing information useful to contemporary disease control programmes.",2008 Apr 18,"['Cottam, Eleanor M.', 'Wadsworth, Jemma', 'Shaw, Andrew E.', 'Rowlands, Rebecca J.', 'Goatley, Lynnette', 'Maan, Sushila', 'Maan, Narender S.', 'Mertens, Peter P. C.', 'Ebert, Katja', 'Li, Yanmin', 'Ryan, Eoin D.', 'Juleff, Nicholas', 'Ferris, Nigel P.', 'Wilesmith, John W.', 'Haydon, Daniel T.', 'King, Donald P.', 'Paton, David J.', 'Knowles, Nick J.']",PLoS Pathog,,,True
444faa5fa90cd457f9f318f5151cc6c93017bae5,PMC,Transmission Pathways of Foot-and-Mouth Disease Virus in the United Kingdom in 2007,http://dx.doi.org/10.1371/journal.ppat.1000050,PMC2277462,18421380,CC BY,"Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols). Here, we show that the outbreaks of FMD in the United Kingdom in August 2007 were caused by a derivative of FMDV O(1) BFS 1860, a virus strain handled at two FMD laboratories located on a single site at Pirbright in Surrey. Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August. Complete genome sequence analysis of FMD viruses conducted in real-time have identified the initial and intermediate sources of these outbreaks and demonstrate the value of such techniques in providing information useful to contemporary disease control programmes.",2008 Apr 18,"['Cottam, Eleanor M.', 'Wadsworth, Jemma', 'Shaw, Andrew E.', 'Rowlands, Rebecca J.', 'Goatley, Lynnette', 'Maan, Sushila', 'Maan, Narender S.', 'Mertens, Peter P. C.', 'Ebert, Katja', 'Li, Yanmin', 'Ryan, Eoin D.', 'Juleff, Nicholas', 'Ferris, Nigel P.', 'Wilesmith, John W.', 'Haydon, Daniel T.', 'King, Donald P.', 'Paton, David J.', 'Knowles, Nick J.']",PLoS Pathog,,,False
f14d0b6eecd99d0bc6afefbb3db486a895ce2efc,PMC,Transmission Pathways of Foot-and-Mouth Disease Virus in the United Kingdom in 2007,http://dx.doi.org/10.1371/journal.ppat.1000050,PMC2277462,18421380,CC BY,"Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols). Here, we show that the outbreaks of FMD in the United Kingdom in August 2007 were caused by a derivative of FMDV O(1) BFS 1860, a virus strain handled at two FMD laboratories located on a single site at Pirbright in Surrey. Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August. Complete genome sequence analysis of FMD viruses conducted in real-time have identified the initial and intermediate sources of these outbreaks and demonstrate the value of such techniques in providing information useful to contemporary disease control programmes.",2008 Apr 18,"['Cottam, Eleanor M.', 'Wadsworth, Jemma', 'Shaw, Andrew E.', 'Rowlands, Rebecca J.', 'Goatley, Lynnette', 'Maan, Sushila', 'Maan, Narender S.', 'Mertens, Peter P. C.', 'Ebert, Katja', 'Li, Yanmin', 'Ryan, Eoin D.', 'Juleff, Nicholas', 'Ferris, Nigel P.', 'Wilesmith, John W.', 'Haydon, Daniel T.', 'King, Donald P.', 'Paton, David J.', 'Knowles, Nick J.']",PLoS Pathog,,,False
330c656592e9917ebc7c9c1703ddaa3d9df809bf,PMC,Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes,http://dx.doi.org/10.1186/1743-422X-5-28,PMC2288602,18282283,CC BY,"BACKGROUND: Members of the Baculoviridae encode two types of proteins that mediate virus:cell membrane fusion and penetration into the host cell. Alignments of primary amino acid sequences indicate that baculovirus fusion proteins of group I nucleopolyhedroviruses (NPV) form the GP64 superfamily. The structure of these viral penetrenes has not been determined. The GP64 superfamily includes the glycoprotein (GP) encoded by members of the Thogotovirus genus of the Orthomyxoviridae. The entry proteins of other baculoviruses, group II NPV and granuloviruses, are class I penetrenes. RESULTS: Class III penetrenes encoded by members of the Rhabdoviridae and Herpesviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Similar sequences and structural/functional motifs that characterize class III penetrenes are located collinearly in GP64 of group I baculoviruses and related glycoproteins encoded by thogotoviruses. Structural models based on a prototypic class III penetrene, vesicular stomatitis virus glycoprotein (VSV G), were established for Thogoto virus (THOV) GP and Autographa california multiple NPV (AcMNPV) GP64 demonstrating feasible cysteine linkages. Glycosylation sites in THOV GP and AcMNPV GP64 appear in similar model locations to the two glycosylation sites of VSV G. CONCLUSION: These results suggest that proteins in the GP64 superfamily are class III penetrenes.",2008 Feb 18,"['Garry, Courtney E', 'Garry, Robert F']",Virol J,,,True
6567692317d79659efda807e54ced960c8588ffb,PMC,Activation of Interleukin-32 Pro-Inflammatory Pathway in Response to Influenza A Virus Infection,http://dx.doi.org/10.1371/journal.pone.0001985,PMC2288676,18414668,CC BY,"BACKGROUND: Interleukin (IL)-32 is a recently described pro-inflammatory cytokine that has been reported to be induced by bacteria treatment in culture cells. Little is known about IL-32 production by exogenous pathogens infection in human individuals. METHODS AND FINDINGS: In this study, we found that IL-32 level was increased by 58.2% in the serum samples from a cohort of 108 patients infected by influenza A virus comparing to that of 115 healthy individuals. Another pro-inflammatory factor cyclooxygenase (COX)-2-associated prostaglandin E2 was also upregulated by 2.7-fold. Expression of IL-32 in influenza A virus infected A549 human lung epithelial cells was blocked by either selective COX-2 inhibitor NS398 or Aspirin, a known anti-inflammatory drug, indicating IL-32 was induced through COX-2 in the inflammatory cascade. Interestingly, we found that COX-2-associate PGE(2) production activated by influenza virus infection was significantly suppressed by over-expression of IL-32 but increased by IL-32-specific siRNA, suggesting there was a feedback mechanism between IL-32 and COX-2. CONCLUSIONS: IL-32 is induced by influenza A virus infection via COX-2 in the inflammatory cascade. Our results provide that IL-32 is a potential target for anti-inflammatory medicine screening.",2008 Apr 16,"['Li, Wei', 'Liu, Yan', 'Mukhtar, Muhammad Mahmood', 'Gong, Rui', 'Pan, Ying', 'Rasool, Sahibzada T.', 'Gao, Yecheng', 'Kang, Lei', 'Hao, Qian', 'Peng, Guiqing', 'Chen, Yanni', 'Chen, Xin', 'Wu, Jianguo', 'Zhu, Ying']",PLoS One,,,True
b61e1ca6b1b5a83aa20344e4832ac9ee1eb1dfa9,PMC,The Cuyahoga Is Still Burning,http://dx.doi.org/10.1289/ehp.11419,PMC2290999,18414602,CC0,,2008 Apr,"['Silbergeld, Ellen K.', 'Graham, Jay P.']",Environ Health Perspect,,,False
4e951550757b4a9f7b9b5167c9774a1113c787e9,PMC,Safety and immunogenicity of an MF59™-adjuvanted subunit influenza vaccine in elderly Chinese subjects,http://dx.doi.org/10.1186/1742-4933-5-2,PMC2291031,18289372,CC BY,"BACKGROUND: The safety and immunogenicity of an MF59™-adjuvanted subunit influenza vaccine (Sub/MF59™; FLUAD(®), Novartis Vaccines) was evaluated among elderly Chinese subjects (≥ 60 years of age). After a preliminary Phase I, open-label study (n = 25) to assess safety 1–14 days post-vaccination, a comparative observer-blind, randomised, controlled clinical trial (n = 600) was performed to assess safety and immunogenicity versus a non-adjuvanted subunit influenza vaccine (Subunit; Agrippal(®), Novartis Vaccines). Subjects were randomised (2:1) to receive Sub/MF59™ or Subunit. RESULTS: Both vaccines were well tolerated, with no vaccine-related serious adverse events reported during the Phase I trial. During the observer-blind study, local and systemic reactions were generally similar for both vaccines 1–22 days post-vaccination; however, injection-site induration was more frequent among the Subunit group (P < 0.05), and mild pain at the injection site and fever were more frequent among Sub/MF59™ recipients (P ≤ 0.005). Both vaccines induced a significant (P < 0.001) increase in geometric mean titres (GMTs) for the three strains tested, versus baseline; GMTs against A/H1N1, A/H3N2 and B were significantly higher in the Sub/MF59™ group (P = 0.034, P < 0.001 and P = 0.005, respectively). GMT ratios against A/H1N1, A/H3N2 and B were also significantly higher in the Sub/MF59™ group (P = 0.038, P < 0.001 and P = 0.006, respectively). Similarly, the percentage of subjects achieving seroprotection or seroconversion on Day 22 was greater for Sub/MF59™ recipients, reaching significance for A/H3N2 (P < 0.001). CONCLUSION: MF59™-adjuvanted subunit influenza vaccine is well tolerated by elderly Chinese subjects and induces a higher level of immunogenicity than a non-adjuvanted subunit influenza vaccine in this population that is at high risk of influenza-related complications. CLINICAL TRIAL REGISTRY: , NCT00310648",2008 Feb 20,"['Li, Rongcheng', 'Fang, Hanhua', 'Li, Yanping', 'Liu, Youping', 'Pellegrini, Michele', 'Podda, Audino']",Immun Ageing,,,True
5e9ccecdd40825f5c30da3a900fc5cf1b063b47d,PMC,Roles of TNF-α gene polymorphisms in the occurrence and progress of SARS-Cov infection: A case-control study,http://dx.doi.org/10.1186/1471-2334-8-27,PMC2291466,18312678,CC BY,"BACKGROUND: Host genetic factors may play a role in the occurrence and progress of SARS-Cov infection. This study was to investigate the relationship between tumor necrosis factor (TNF)-α gene polymorphisms with the occurrence of SARS-CoV infection and its role in prognosis of patients with lung interstitial fibrosis and femoral head osteonecrosis. METHODS: The association between genetic polymorphisms of TNF-α gene and susceptibility to severe acute respiratory syndromes (SARS) was conducted in a hospital-based case-control study including 75 SARS patients, 41 health care workers and 92 healthy controls. Relationships of TNF-α gene polymorphisms with interstitial lung fibrosis and femoral head osteonecrosis were carried out in two case-case studies in discharged SARS patients. PCR sequencing based typing (PCR-SBT) method was used to determine the polymorphisms of TNF-α gene in locus of the promoter region and univariate logistic analysis was conducted in analyzing the collected data. RESULTS: Compared to TT genotype, the CT genotype at the -204 locus was found associated with a protective effect on SARS with OR(95%CI) of 0.95(0.90–0.99). Also, TT genotype, CT and CC were found associated with a risk effect on femoral head necrosis with ORs(95%CI) of 5.33(1.39–20.45) and 5.67(2.74–11.71), respectively and the glucocorticoid adjusted OR of CT was 5.25(95%CI 1.18–23.46) and the combined (CT and CC) genotype OR was 6.0 (95%CI 1.60–22.55) at -1031 site of TNF-α gene. At the same time, the -863 AC genotype was manifested as another risk effect associated with femoral head necrosis with OR(95%CI) of 6.42(1.53–26.88) and the adjusted OR was 8.40(95%CI 1.76–40.02) in cured SARS patients compared to CC genotype. CONCLUSION: SNPs of TNF-α gene of promoter region may not associate with SARS-CoV infection. And these SNPs may not affect interstitial lung fibrosis in cured SARS patients. However, the -1031CT/CC and -863 AC genotypes may be risk factors of femoral head necrosis in discharged SARS patients.",2008 Feb 29,"['Wang, Shixin', 'Wei, Maoti', 'Han, Yi', 'Zhang, Keju', 'He, Li', 'Yang, Zhen', 'Su, Bing', 'Zhang, Zhilun', 'Hu, Yilan', 'Hui, Wuli']",BMC Infect Dis,,,True
6b18741fd5c6ab895acb11a559286c68b43eb9d4,PMC,Bioinformatics in China: A Personal Perspective,http://dx.doi.org/10.1371/journal.pcbi.1000020,PMC2291564,18437216,CC BY,,2008 Apr 25,"['Wei, Liping', 'Yu, Jun']",PLoS Comput Biol,,,True
f40d65d9dcb0b71bd266e62f77bc51d4c449eed1,PMC,The United States and Canada as a coupled epidemiological system: An example from hepatitis A,http://dx.doi.org/10.1186/1471-2334-8-23,PMC2292190,18307785,CC BY,"BACKGROUND: Hepatitis A (HA) is a low-incidence, non-endemic disease in Canada and the United States (US). However, a large difference in HA incidence between Canada and HA-endemic countries has made travel an important contributor to hepatitis A prevalence in Canada. There is also a (smaller) incidence differential between Canada and the US. Although the US has only moderately higher HA incidence, the volume of travel by Canadians to the US is many times higher than travel volume to endemic countries. Hence, travel to the US may constitute a source of low to moderate risk for Canadian travelers. To our knowledge, travel to the US has never been included as a potential risk factor for HA infection in Canadian epidemiologic analyses. The objective of this study was to use dynamic models to investigate the possible effects on hepatitis A incidence in Canada due to (1) implementing vaccination in the US, and (2) varying the volume of travel by Canadians to the US. METHODS: We developed and analyzed age-structured compartmental models for the transmission and vaccination of hepatitis A, for both Canada and the US. Models were parameterized using data on seroprevalence, case reporting, and travel patterns. The potential effect of hepatitis A prevalence in the US on hepatitis A prevalence in Canada was captured through a term representing infection of Canadians due to travel in the US. RESULTS: The model suggests that approximately 22% of HA cases in Canada in the mid 1990s may have been attributable to travel to the US. A universal vaccination programme that attained 70% coverage in young children in the US in the mid 1990s could have reduced Canadian incidence by 21% within 5 years. CONCLUSION: Since not all necessary data were available to parameterize the model, the results should be considered exploratory. However, the analysis shows that, under plausible assumptions, the US may be more important for determining HA prevalence in Canada than is currently supposed. As international travel continues to grow, making vaccination policies ever more relevant to populations beyond a country's borders, such multi-country models will most likely come into wider use as predictive aids for policy development.",2008 Feb 28,"['Amariei, Raluca', 'Willms, Allan R', 'Bauch, Chris T']",BMC Infect Dis,,,True
0e7e8aa9e5d952e8486bc9599764a9fcddd7f579,PMC,Improved production of human type II procollagen in the yeast Pichia pastoris in shake flasks by a wireless-controlled fed-batch system,http://dx.doi.org/10.1186/1472-6750-8-33,PMC2315644,18371201,CC BY,"BACKGROUND: Here we describe a new technical solution for optimization of Pichia pastoris shake flask cultures with the example of production of stable human type II collagen. Production of recombinant proteins in P. pastoris is usually performed by controlling gene expression with the strong AOX1 promoter, which is induced by addition of methanol. Optimization of processes using the AOX1 promoter in P. pastoris is generally done in bioreactors by fed-batch fermentation with a controlled continuous addition of methanol for avoiding methanol toxification and carbon/energy starvation. The development of feeding protocols and the study of AOX1-controlled recombinant protein production have been largely made in shake flasks, although shake flasks have very limited possibilities for measurement and control. RESULTS: By applying on-line pO(2 )monitoring we demonstrate that the widely used pulse feeding of methanol results in long phases of methanol exhaustion and consequently low expression of AOX1 controlled genes. Furthermore, we provide a solution to apply the fed-batch strategy in shake flasks. The presented solution applies a wireless feeding unit which can be flexibly positioned and allows the use of computer-controlled feeding profiles. By using the human collagen II as an example we show that a quasi-continuous feeding profile, being the simplest way of a fed-batch fermentation, results in a higher production level of human collagen II. Moreover, the product has a higher proteolytic stability compared to control cultures due to the increased expression of human collagen prolyl 4-hydroxylase as monitored by mRNA and protein levels. CONCLUSION: The recommended standard protocol for methanol addition in shake flasks using pulse feeding is non-optimal and leads to repeated long phases of methanol starvation. The problem can be solved by applying the fed-batch technology. The presented wireless feeding unit, together with an on-line monitoring system offers a flexible, simple, and low-cost solution for initial optimization of the production in shake flasks which can be performed in parallel. By this way the fed-batch strategy can be applied from the early screening steps also in laboratories which do not have access to high-cost and complicated bioreactor systems.",2008 Mar 27,"['Ruottinen, Maria', 'Bollok, Monika', 'Kögler, Martin', 'Neubauer, Antje', 'Krause, Mirja', 'Hämäläinen, Eija-Riitta', 'Myllyharju, Johanna', 'Vasala, Antti', 'Neubauer, Peter']",BMC Biotechnol,,,True
95beff3302bdaccd3ce824cdbf374a20b1a987b8,PMC,SARS-Coronavirus Replication/Transcription Complexes Are Membrane-Protected and Need a Host Factor for Activity In Vitro,http://dx.doi.org/10.1371/journal.ppat.1000054,PMC2322833,18451981,CC BY,"SARS-coronavirus (SARS-CoV) replication and transcription are mediated by a replication/transcription complex (RTC) of which virus-encoded, non-structural proteins (nsps) are the primary constituents. The 16 SARS-CoV nsps are produced by autoprocessing of two large precursor polyproteins. The RTC is believed to be associated with characteristic virus-induced double-membrane structures in the cytoplasm of SARS-CoV-infected cells. To investigate the link between these structures and viral RNA synthesis, and to dissect RTC organization and function, we isolated active RTCs from infected cells and used them to develop the first robust assay for their in vitro activity. The synthesis of genomic RNA and all eight subgenomic mRNAs was faithfully reproduced by the RTC in this in vitro system. Mainly positive-strand RNAs were synthesized and protein synthesis was not required for RTC activity in vitro. All RTC activity, enzymatic and putative membrane-spanning nsps, and viral RNA cosedimented with heavy membrane structures. Furthermore, the pelleted RTC required the addition of a cytoplasmic host factor for reconstitution of its in vitro activity. Newly synthesized subgenomic RNA appeared to be released, while genomic RNA remained predominantly associated with the RTC-containing fraction. RTC activity was destroyed by detergent treatment, suggesting an important role for membranes. The RTC appeared to be protected by membranes, as newly synthesized viral RNA and several replicase/transcriptase subunits were protease- and nuclease-resistant and became susceptible to degradation only upon addition of a non-ionic detergent. Our data establish a vital functional dependence of SARS-CoV RNA synthesis on virus-induced membrane structures.",2008 May 2,"['van Hemert, Martijn J.', 'van den Worm, Sjoerd H. E.', 'Knoops, Kèvin', 'Mommaas, A. Mieke', 'Gorbalenya, Alexander E.', 'Snijder, Eric J.']",PLoS Pathog,,,True
b281ffd13e1ca8492cc60ae608b6b24a7be46a1f,PMC,Methods for simultaneously identifying coherent local clusters with smooth global patterns in gene expression profiles,http://dx.doi.org/10.1186/1471-2105-9-155,PMC2322988,18366693,CC BY,"BACKGROUND: The hierarchical clustering tree (HCT) with a dendrogram [1] and the singular value decomposition (SVD) with a dimension-reduced representative map [2] are popular methods for two-way sorting the gene-by-array matrix map employed in gene expression profiling. While HCT dendrograms tend to optimize local coherent clustering patterns, SVD leading eigenvectors usually identify better global grouping and transitional structures. RESULTS: This study proposes a flipping mechanism for a conventional agglomerative HCT using a rank-two ellipse (R2E, an improved SVD algorithm for sorting purpose) seriation by Chen [3] as an external reference. While HCTs always produce permutations with good local behaviour, the rank-two ellipse seriation gives the best global grouping patterns and smooth transitional trends. The resulting algorithm automatically integrates the desirable properties of each method so that users have access to a clustering and visualization environment for gene expression profiles that preserves coherent local clusters and identifies global grouping trends. CONCLUSION: We demonstrate, through four examples, that the proposed method not only possesses better numerical and statistical properties, it also provides more meaningful biomedical insights than other sorting algorithms. We suggest that sorted proximity matrices for genes and arrays, in addition to the gene-by-array expression matrix, can greatly aid in the search for comprehensive understanding of gene expression structures. Software for the proposed methods can be obtained at .",2008 Mar 20,"['Tien, Yin-Jing', 'Lee, Yun-Shien', 'Wu, Han-Ming', 'Chen, Chun-Houh']",BMC Bioinformatics,,,True
46795b2f533aa0d3e20b1df752cf6c18455ad862,PMC,Pathogen Discovery,http://dx.doi.org/10.1371/journal.ppat.1000002,PMC2329853,18437241,CC BY,,2008 Apr 25,"Lipkin, W. Ian",PLoS Pathog,,,True
0e1c072b035756104151484e6548cac0517cc5f2,PMC,Synonym set extraction from the biomedical literature by lexical pattern discovery,http://dx.doi.org/10.1186/1471-2105-9-159,PMC2335115,18366721,CC BY,"BACKGROUND: Although there are a large number of thesauri for the biomedical domain many of them lack coverage in terms and their variant forms. Automatic thesaurus construction based on patterns was first suggested by Hearst [1], but it is still not clear how to automatically construct such patterns for different semantic relations and domains. In particular it is not certain which patterns are useful for capturing synonymy. The assumption of extant resources such as parsers is also a limiting factor for many languages, so it is desirable to find patterns that do not use syntactical analysis. Finally to give a more consistent and applicable result it is desirable to use these patterns to form synonym sets in a sound way. RESULTS: We present a method that automatically generates regular expression patterns by expanding seed patterns in a heuristic search and then develops a feature vector based on the occurrence of term pairs in each developed pattern. This allows for a binary classifications of term pairs as synonymous or non-synonymous. We then model this result as a probability graph to find synonym sets, which is equivalent to the well-studied problem of finding an optimal set cover. We achieved 73.2% precision and 29.7% recall by our method, out-performing hand-made resources such as MeSH and Wikipedia. CONCLUSION: We conclude that automatic methods can play a practical role in developing new thesauri or expanding on existing ones, and this can be done with only a small amount of training data and no need for resources such as parsers. We also concluded that the accuracy can be improved by grouping into synonym sets.",2008 Mar 24,"['McCrae, John', 'Collier, Nigel']",BMC Bioinformatics,,,True
5ed3b0cd33b9af56879a3b5f10d6b7399ae86785,PMC,Nanopolymers improve delivery of exon skipping oligonucleotides and concomitant dystrophin expression in skeletal muscle of mdx mice,http://dx.doi.org/10.1186/1472-6750-8-35,PMC2362111,18384691,CC BY,"BACKGROUND: Exon skipping oligonucleotides (ESOs) of 2'O-Methyl (2'OMe) and morpholino chemistry have been shown to restore dystrophin expression in muscle fibers from the mdx mouse, and are currently being tested in phase I clinical trials for Duchenne Muscular Dystrophy (DMD). However, ESOs remain limited in their effectiveness because of an inadequate delivery profile. Synthetic cationic copolymers of poly(ethylene imine) (PEI) and poly(ethylene glycol) (PEG) are regarded as effective agents for enhanced delivery of nucleic acids in various applications. RESULTS: We examined whether PEG-PEI copolymers can facilitate ESO-mediated dystrophin expression after intramuscular injections into tibialis anterior (TA) muscles of mdx mice. We utilized a set of PEG-PEI copolymers containing 2 kDa PEI and either 550 Da or 5 kDa PEG, both of which bind 2'OMe ESOs with high affinity and form stable nanoparticulates with a relatively low surface charge. Three weekly intramuscular injections of 5 μg of ESO complexed with PEI2K-PEG550 copolymers resulted in about 500 dystrophin-positive fibers and about 12% of normal levels of dystrophin expression at 3 weeks after the initial injection, which is significantly greater than for injections of ESO alone, which are known to be almost completely ineffective. In an effort to enhance biocompatibility and cellular uptake, the PEI2K-PEG550 and PEI2K-PEG5K copolymers were functionalized by covalent conjugation with nanogold (NG) or adsorbtion of colloidal gold (CG), respectively. Surprisingly, using the same injection and dosing regimen, we found no significant difference in dystrophin expression by Western blot between the NG-PEI2K-PEG550, CG-PEI2K-PEG5K, and non-functionalized PEI2K-PEG550 copolymers. Dose-response experiments using the CG-PEI2K-PEG5K copolymer with total ESO ranging from 3–60 μg yielded a maximum of about 15% dystrophin expression. Further improvements in dystrophin expression up to 20% of normal levels were found at 6 weeks after 10 twice-weekly injections of the NG-PEI2K-PEG550 copolymer complexed with 5 μg of ESO per injection. This injection and dosing regimen showed over 1000 dystrophin-positive fibers. H&E staining of all treated muscle groups revealed no overt signs of cytotoxicity. CONCLUSION: We conclude that PEGylated PEI2K copolymers are efficient carriers for local delivery of 2'OMe ESOs and warrant further development as potential therapeutics for treatment of DMD.",2008 Apr 2,"['Williams, Jason H', 'Schray, Rebecca C', 'Sirsi, Shashank R', 'Lutz, Gordon J']",BMC Biotechnol,,,True
702d0144bdeae0782bbebcbe41d432fa7ae41415,PMC,Functional Analysis of the 5′ Genomic Sequence of a Bovine Norovirus,http://dx.doi.org/10.1371/journal.pone.0002169,PMC2364642,18478070,CC BY,"BACKGROUND: Jena Virus (JV), a bovine Norovirus, causes enteric disease in cattle and represents a potential model for the study of enteric norovirus infection and pathogenesis. The positive sense RNA genome of JV is organised into ORF1 (non-structural proteins), ORF2 (major capsid protein) and ORF3 (minor capsid protein). The lack of a cell culture system for studying JV replication has meant that work to date has relied upon in vitro systems to study non-structural protein synthesis and processing. PRINCIPAL FINDINGS: Only two of the three major ORF1 proteins were identified (p110 and 2C) following in vitro translation of JV RNA, the N-term protein was not detected. The N-term encoding genomic sequence (5′GS) was tested for IRES-like function in a bi-cistronic system and displayed no evidence of IRES-like activity. The site of translation initiation in JV was determined to be at the predicted nucleotide 22. Following the insertion of an epitope within the 5′GS the JV N-term protein was identified in vitro and within RNA transfected cells. CONCLUSIONS: The in vitro transcription/translation system is currently the best system for analysing protein synthesis and processing in JV. Unlike similarly studied human noroviruses JV initially did not appear to express the N-terminal protein, presenting the possibility that the encoding RNA sequence had a regulatory function, most likely involved in translation initiation in an IRES-like manner. This was not the case and, following determination of the site of translation initiation the N-term protein was detected using an epitope tag, both in vitro and in vivo. Although slightly larger than predicted the N-term protein was detected in a processed form in vivo, thus not only demonstrating initial translation of the ORF1 polyprotein but also activity of the viral protease. These findings indicate that the block to noroviral replication in cultured cells lies elsewhere.",2008 May 14,"['Salim, Omar', 'Clarke, Ian N.', 'Lambden, Paul R.']",PLoS One,,,True
d94115064a8168415d634f654869a4009e4c3c70,PMC,Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households,http://dx.doi.org/10.1371/journal.pone.0002101,PMC2364646,18461182,CC0,"BACKGROUND: There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomized to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms. Adherence to interventions was variable. CONCLUSIONS/SIGNIFICANCE: The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learnt from this pilot have informed changes for the main study in 2008. TRIAL REGISTRATION: ClinicalTrials.gov NCT00425893 HKClinicalTrials.com HKCTR-365",2008 May 7,"['Cowling, Benjamin J.', 'Fung, Rita O. P.', 'Cheng, Calvin K. Y.', 'Fang, Vicky J.', 'Chan, Kwok Hung', 'Seto, Wing Hong', 'Yung, Raymond', 'Chiu, Billy', 'Lee, Paco', 'Uyeki, Timothy M.', 'Houck, Peter M.', 'Peiris, J. S. Malik', 'Leung, Gabriel M.']",PLoS One,,,True
3d2962558f0a2ed4ddc00989168efe60856bd792,PMC,Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households,http://dx.doi.org/10.1371/journal.pone.0002101,PMC2364646,18461182,CC0,"BACKGROUND: There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomized to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms. Adherence to interventions was variable. CONCLUSIONS/SIGNIFICANCE: The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learnt from this pilot have informed changes for the main study in 2008. TRIAL REGISTRATION: ClinicalTrials.gov NCT00425893 HKClinicalTrials.com HKCTR-365",2008 May 7,"['Cowling, Benjamin J.', 'Fung, Rita O. P.', 'Cheng, Calvin K. Y.', 'Fang, Vicky J.', 'Chan, Kwok Hung', 'Seto, Wing Hong', 'Yung, Raymond', 'Chiu, Billy', 'Lee, Paco', 'Uyeki, Timothy M.', 'Houck, Peter M.', 'Peiris, J. S. Malik', 'Leung, Gabriel M.']",PLoS One,,,True
eed4a68d4e44f9887b3219ad5813eed5f0c4d42b,PMC,Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households,http://dx.doi.org/10.1371/journal.pone.0002101,PMC2364646,18461182,CC0,"BACKGROUND: There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomized to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms. Adherence to interventions was variable. CONCLUSIONS/SIGNIFICANCE: The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learnt from this pilot have informed changes for the main study in 2008. TRIAL REGISTRATION: ClinicalTrials.gov NCT00425893 HKClinicalTrials.com HKCTR-365",2008 May 7,"['Cowling, Benjamin J.', 'Fung, Rita O. P.', 'Cheng, Calvin K. Y.', 'Fang, Vicky J.', 'Chan, Kwok Hung', 'Seto, Wing Hong', 'Yung, Raymond', 'Chiu, Billy', 'Lee, Paco', 'Uyeki, Timothy M.', 'Houck, Peter M.', 'Peiris, J. S. Malik', 'Leung, Gabriel M.']",PLoS One,,,True
af1eb3ba403f1baa08d494a446fab866d82e69d9,PMC,Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households,http://dx.doi.org/10.1371/journal.pone.0002101,PMC2364646,18461182,CC0,"BACKGROUND: There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomized to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms. Adherence to interventions was variable. CONCLUSIONS/SIGNIFICANCE: The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learnt from this pilot have informed changes for the main study in 2008. TRIAL REGISTRATION: ClinicalTrials.gov NCT00425893 HKClinicalTrials.com HKCTR-365",2008 May 7,"['Cowling, Benjamin J.', 'Fung, Rita O. P.', 'Cheng, Calvin K. Y.', 'Fang, Vicky J.', 'Chan, Kwok Hung', 'Seto, Wing Hong', 'Yung, Raymond', 'Chiu, Billy', 'Lee, Paco', 'Uyeki, Timothy M.', 'Houck, Peter M.', 'Peiris, J. S. Malik', 'Leung, Gabriel M.']",PLoS One,,,False
45413d24ce4a3a305bd77754c506c525d308396b,PMC,Real Time Bayesian Estimation of the Epidemic Potential of Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0002185,PMC2366072,18478118,CC BY,"BACKGROUND: Fast changes in human demographics worldwide, coupled with increased mobility, and modified land uses make the threat of emerging infectious diseases increasingly important. Currently there is worldwide alert for H5N1 avian influenza becoming as transmissible in humans as seasonal influenza, and potentially causing a pandemic of unprecedented proportions. Here we show how epidemiological surveillance data for emerging infectious diseases can be interpreted in real time to assess changes in transmissibility with quantified uncertainty, and to perform running time predictions of new cases and guide logistics allocations. METHODOLOGY/PRINCIPAL FINDINGS: We develop an extension of standard epidemiological models, appropriate for emerging infectious diseases, that describes the probabilistic progression of case numbers due to the concurrent effects of (incipient) human transmission and multiple introductions from a reservoir. The model is cast in terms of surveillance observables and immediately suggests a simple graphical estimation procedure for the effective reproductive number R (mean number of cases generated by an infectious individual) of standard epidemics. For emerging infectious diseases, which typically show large relative case number fluctuations over time, we develop a Bayesian scheme for real time estimation of the probability distribution of the effective reproduction number and show how to use such inferences to formulate significance tests on future epidemiological observations. CONCLUSIONS/SIGNIFICANCE: Violations of these significance tests define statistical anomalies that may signal changes in the epidemiology of emerging diseases and should trigger further field investigation. We apply the methodology to case data from World Health Organization reports to place bounds on the current transmissibility of H5N1 influenza in humans and establish a statistical basis for monitoring its evolution in real time.",2008 May 14,"['Bettencourt, Luís M. A.', 'Ribeiro, Ruy M.']",PLoS One,,,True
2000b56ab7a60199d3bbb2148295370ae87b3d58,PMC,Real Time Bayesian Estimation of the Epidemic Potential of Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0002185,PMC2366072,18478118,CC BY,"BACKGROUND: Fast changes in human demographics worldwide, coupled with increased mobility, and modified land uses make the threat of emerging infectious diseases increasingly important. Currently there is worldwide alert for H5N1 avian influenza becoming as transmissible in humans as seasonal influenza, and potentially causing a pandemic of unprecedented proportions. Here we show how epidemiological surveillance data for emerging infectious diseases can be interpreted in real time to assess changes in transmissibility with quantified uncertainty, and to perform running time predictions of new cases and guide logistics allocations. METHODOLOGY/PRINCIPAL FINDINGS: We develop an extension of standard epidemiological models, appropriate for emerging infectious diseases, that describes the probabilistic progression of case numbers due to the concurrent effects of (incipient) human transmission and multiple introductions from a reservoir. The model is cast in terms of surveillance observables and immediately suggests a simple graphical estimation procedure for the effective reproductive number R (mean number of cases generated by an infectious individual) of standard epidemics. For emerging infectious diseases, which typically show large relative case number fluctuations over time, we develop a Bayesian scheme for real time estimation of the probability distribution of the effective reproduction number and show how to use such inferences to formulate significance tests on future epidemiological observations. CONCLUSIONS/SIGNIFICANCE: Violations of these significance tests define statistical anomalies that may signal changes in the epidemiology of emerging diseases and should trigger further field investigation. We apply the methodology to case data from World Health Organization reports to place bounds on the current transmissibility of H5N1 influenza in humans and establish a statistical basis for monitoring its evolution in real time.",2008 May 14,"['Bettencourt, Luís M. A.', 'Ribeiro, Ruy M.']",PLoS One,,,True
7a5478dfe79fbf67551ac9261f190d899ba719b3,PMC,IL-12 RB1 Genetic Variants Contribute to Human Susceptibility to Severe Acute Respiratory Syndrome Infection among Chinese,http://dx.doi.org/10.1371/journal.pone.0002183,PMC2367437,18478121,CC BY,"BACKGROUND: Cytokines play important roles in antiviral action. We examined whether polymorphisms of interleukin (IL)-12 receptor B1 (IL-12RB1) affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). METHODS: A case-control study was carried out in Chinese SARS patients and healthy controls. The genotypes of 4SNPs on IL-12 RB1 gene, +705A/G,+1158T/C, +1196G/C and +1664 C/T, were determined by PCR-RFLP. Haplotypes were estimated from the genotype data using the expectation-maximisation algorithm. RESULTS: Comparison between patients and close contacts showed that individuals with the +1664 C/T (CT and TT) genotype had a 2.09-fold (95% confidence interval [CI], 1.90–7.16) and 2.34-fold (95% CI, 1.79–13.37) increased risk of developing SARS, respectively. For any of the other three polymorphisms, however, no significant difference can be detected in allele or genotype frequencies between patients and controls. Additionally, estimation of the frequencies of multiple-locus haplotypes revealed potential risk haplotypes (GCCT) for SARS infection. CONCLUSIONS: Our data indicate that genetic variants of IL12RB1confer genetic susceptibility to SARS infection, but not necessary associated with the progression of the disease in Chinese population.",2008 May 14,"['Tang, Fang', 'Liu, Wei', 'Zhang, Fang', 'Xin, Zhong-Tao', 'Wei, Mao-Ti', 'Zhang, Pan-He', 'Yang, Hong', 'Ly, Hinh', 'Cao, Wu-Chun']",PLoS One,,,True
92ed9b003b6c24304a7bad059d22c286735ed839,PMC,"DetectiV: visualization, normalization and significance testing for pathogen-detection microarray data",http://dx.doi.org/10.1186/gb-2007-8-9-r190,PMC2375028,17868443,CC BY,"DNA microarrays offer the possibility of testing for the presence of thousands of micro-organisms in a single experiment. However, there is a lack of reliable bioinformatics tools for the analysis of such data. We have developed DetectiV, a package for the statistical software R. DetectiV offers powerful yet simple visualization, normalization and significance testing tools. We show that DetectiV performs better than previously published software on a large, publicly available dataset.",2007 Sep 14,"['Watson, Michael', 'Dukes, Juliet', 'Abu-Median, Abu-Bakr', 'King, Donald P', 'Britton, Paul']",Genome Biol,,,True
857137889eef45edb1a66c1950f0e0ca27ad63a4,PMC,Viral Control of Mitochondrial Apoptosis,http://dx.doi.org/10.1371/journal.ppat.1000018,PMC2376094,18516228,CC BY,"Throughout the process of pathogen–host co-evolution, viruses have developed a battery of distinct strategies to overcome biochemical and immunological defenses of the host. Thus, viruses have acquired the capacity to subvert host cell apoptosis, control inflammatory responses, and evade immune reactions. Since the elimination of infected cells via programmed cell death is one of the most ancestral defense mechanisms against infection, disabling host cell apoptosis might represent an almost obligate step in the viral life cycle. Conversely, viruses may take advantage of stimulating apoptosis, either to kill uninfected cells from the immune system, or to induce the breakdown of infected cells, thereby favoring viral dissemination. Several viral polypeptides are homologs of host-derived apoptosis-regulatory proteins, such as members of the Bcl-2 family. Moreover, viral factors with no homology to host proteins specifically target key components of the apoptotic machinery. Here, we summarize the current knowledge on the viral modulation of mitochondrial apoptosis, by focusing in particular on the mechanisms by which viral proteins control the host cell death apparatus.",2008 May 30,"['Galluzzi, Lorenzo', 'Brenner, Catherine', 'Morselli, Eugenia', 'Touat, Zahia', 'Kroemer, Guido']",PLoS Pathog,,,True
235855da90347b259f4d6b244821f3c1c264c04e,PMC,Expression of Foot-and-Mouth Disease Virus Capsid Proteins in Silkworm-Baculovirus Expression System and Its Utilization as a Subunit Vaccine,http://dx.doi.org/10.1371/journal.pone.0002273,PMC2386233,18509464,CC BY,"BACKGROUND: Foot-and-mouth disease (FMD) is a highly contagious disease of livestock that causes severe economic loss in susceptible cloven-hoofed animals. Although the traditional inactivated vaccine has been proved effective, it may lead to a new outbreak of FMD because of either incomplete inactivation of FMDV or the escape of live virus from vaccine production workshop. Thus, it is urgent to develop a novel FMDV vaccine that is safer, more effective and more economical than traditional vaccines. METHODOLOGY AND PRINCIPAL FINDINGS: A recombinant silkworm baculovirus Bm-P12A3C which contained the intact P1-2A and 3C protease coding regions of FMDV Asia 1/HNK/CHA/05 was developed. Indirect immunofluorescence test and sandwich-ELISA were used to verify that Bm-P12A3C could express the target cassette. Expression products from silkworm were diluted to 30 folds and used as antigen to immunize cattle. Specific antibody was induced in all vaccinated animals. After challenge with virulent homologous virus, four of the five animals were completely protected, and clinical symptoms were alleviated and delayed in the remaining one. Furthermore, a PD(50) (50% bovine protective dose) test was performed to assess the bovine potency of the subunit vaccine. The result showed the subunit vaccine could achieve 6.34 PD(50) per dose. CONCLUSION: The results suggest that this strategy might be used to develop the new subunit FMDV vaccine.",2008 May 28,"['Li, Zhiyong', 'Yi, Yongzhu', 'Yin, Xiangping', 'Zhang, Zhifang', 'Liu, Jixing']",PLoS One,,,True
b67b75854801b20d8d89d71adf85199ec70c3daa,PMC,A flexibly shaped space-time scan statistic for disease outbreak detection and monitoring,http://dx.doi.org/10.1186/1476-072X-7-14,PMC2386448,18402711,CC BY,"BACKGROUND: Early detection of disease outbreaks enables public health officials to implement disease control and prevention measures at the earliest possible time. A time periodic geographical disease surveillance system based on a cylindrical space-time scan statistic has been used extensively for disease surveillance along with the SaTScan software. In the purely spatial setting, many different methods have been proposed to detect spatial disease clusters. In particular, some spatial scan statistics are aimed at detecting irregularly shaped clusters which may not be detected by the circular spatial scan statistic. RESULTS: Based on the flexible purely spatial scan statistic, we propose a flexibly shaped space-time scan statistic for early detection of disease outbreaks. The performance of the proposed space-time scan statistic is compared with that of the cylindrical scan statistic using benchmark data. In order to compare their performances, we have developed a space-time power distribution by extending the purely spatial bivariate power distribution. Daily syndromic surveillance data in Massachusetts, USA, are used to illustrate the proposed test statistic. CONCLUSION: The flexible space-time scan statistic is well suited for detecting and monitoring disease outbreaks in irregularly shaped areas.",2008 Apr 11,"['Takahashi, Kunihiko', 'Kulldorff, Martin', 'Tango, Toshiro', 'Yih, Katherine']",Int J Health Geogr,,,True
3f6a8fc2249ec3b9bc431c5eded7f6234c75c49d,PMC,The effect of network mixing patterns on epidemic dynamics and the efficacy of disease contact tracing,http://dx.doi.org/10.1098/rsif.2007.1272,PMC2386895,18055417,CC BY,"In networks, nodes may preferentially contact other nodes with similar (assortatively mixed) or dissimilar (disassortatively mixed) numbers of contacts. Different patterns of contact support different epidemic dynamics, potentially affecting the efficacy of control measures such as contact tracing, which aims to identify and isolate nodes with infectious contacts. We used stochastic simulations to investigate the effects of mixing patterns on epidemic dynamics and contact-tracing efficacy. For uncontrolled epidemics, outbreaks occur at lower infection rates for more assortatively mixed networks, with faster initial epidemic growth rate and shorter epidemic duration than for disassortatively mixed networks. Contact tracing performs better for assortative mixing where epidemic size is large and tracing rate low, but it performs better for disassortative mixing at higher contact rates. For assortatively mixed networks, disease spreads first to highly connected nodes, but this is balanced by contact tracing quickly identifying these same nodes. The converse is true for disassortative mixing, where both disease and tracing are less likely to target highly connected nodes. For small epidemics, contact tracing is more effective on disassortative networks due to the greater resilience of assortative networks to link removal. Multi-step contact tracing is more effective than single-step tracing for assortative mixing, but this effect is smaller for disassortatively mixed networks.",2008 Jul 6,"['Kiss, Istvan Z', 'Green, Darren M', 'Kao, Rowland R']",J R Soc Interface,,,True
646484c8081b3f1bf336bae89411c2aa86885788,PMC,General Practice and Pandemic Influenza: A Framework for Planning and Comparison of Plans in Five Countries,http://dx.doi.org/10.1371/journal.pone.0002269,PMC2386973,18509538,CC BY,"BACKGROUND: Although primary health care, and in particular, general practice will be at the frontline in the response to pandemic influenza, there are no frameworks to guide systematic planning for this task or to appraise available plans for their relevance to general practice. We aimed to develop a framework that will facilitate planning for general practice, and used it to appraise pandemic plans from Australia, England, USA, New Zealand and Canada. METHODOLOGY/PRINCIPAL FINDINGS: We adapted the Haddon matrix to develop the framework, populating its cells through a multi-method study that incorporated the peer-reviewed and grey literature, interviews with general practitioners, practice nurses and senior decision-makers, and desktop simulation exercises. We used the framework to analyse 89 publicly-available jurisdictional plans at similar managerial levels in the five countries. The framework identifies four functional domains: clinical care for influenza and other needs, public health responsibilities, the internal environment and the macro-environment of general practice. No plan addressed all four domains. Most plans either ignored or were sketchy about non-influenza clinical needs, and about the contribution of general practice to public health beyond surveillance. Collaborations between general practices were addressed in few plans, and inter-relationships with the broader health system, even less frequently. CONCLUSIONS: This is the first study to provide a framework to guide general practice planning for pandemic influenza. The framework helped identify critical shortcomings in available plans. Engaging general practice effectively in planning is challenging, particularly where governance structures for primary health care are weak. We identify implications for practice and for research.",2008 May 28,"['Patel, Mahomed S.', 'Phillips, Christine B.', 'Pearce, Christopher', 'Kljakovic, Marjan', 'Dugdale, Paul', 'Glasgow, Nicholas']",PLoS One,,,True
f080c95434a5112c5e2da4e3f93131fed6207fe7,PMC,"Gene expression analyses in Atlantic salmon challenged with infectious salmon anemia virus reveal differences between individuals with early, intermediate and late mortality",http://dx.doi.org/10.1186/1471-2164-9-179,PMC2387173,18423000,CC BY,"BACKGROUND: Infectious salmon anemia virus (ISAV) causes a multisystemic disease responsible for severe losses in salmon aquaculture. Better understanding of factors that explain variations in resistance between individuals and families is essential for development of strategies for disease control. To approach this, we compared global gene expression using microarrays in fish dying early and late in the time course following infection from a highly pathogenic ISAV. RESULTS: Tissues (gill, heart, liver and spleen) from infected Atlantic salmon (cohabitation, ISAV Glesvaer 2/90 isolate) were collected from three stages over the time course of the experiment; early (EM, 0–10% cumulative mortality (CM), 21–25 days post-infection (DPI)), intermediate (IM, 35–55% CM, 28–31 DPI) and late (LM, 75–85% CM, 37–48 DPI) mortality. Viral loads were equal in EM and IM but dropped markedly in LM fish. Gene expression analyses using a 1.8 K salmonid fish cDNA microarray (SFA2.0) and real-time qPCR revealed a large group of genes highly up-regulated across tissues in EM, which were mainly implicated in innate antiviral responses and cellular stress. Despite equal levels of MHC class I in EM and LM, increase of splenic and cardiac expression of immunoglobulin-like genes was found only in LM while a suite of adaptive immunity markers were activated already in IM. The hepatic responses to ISAV were characterized by difference between EM and LM in expression of chaperones and genes involved in eicosanoid metabolism. To develop classification of high and low resistance phenotypes based on a small number of genes, we processed results from qPCR analyses of liver using a linear discriminant analysis. Four genes (5-lipoxygenase activating protein, cytochrome P450 2K4-1, galectin-9 and annexin A1) were sufficient for correct assignment of individuals to EM, LM and uninfected groups, while IM was inseparable from EM. Three of four prognostic markers are involved in metabolism of inflammatory regulators. CONCLUSION: This study adds to the understanding of molecular determinants for resistance to acute ISAV infection. The most susceptible individuals were characterized by high viral replication and dramatic activation of innate immune responses, which did not provide protection. The ability to endure high levels of infection for sustained periods could be associated with lower inflammatory responses while subsequent protection and viral clearance was most likely conferred by activation of adaptive immunity.",2008 Apr 18,"['Jørgensen, Sven Martin', 'Afanasyev, Sergey', 'Krasnov, Aleksei']",BMC Genomics,,,True
578d296ec1f6acc01c08cc5a9861bac6d47ddfda,PMC,Cellular Proteins in Influenza Virus Particles,http://dx.doi.org/10.1371/journal.ppat.1000085,PMC2390764,18535660,CC BY,"Virions are thought to contain all the essential proteins that govern virus egress from the host cell and initiation of replication in the target cell. It has been known for some time that influenza virions contain nine viral proteins; however, analyses of other enveloped viruses have revealed that proteins from the host cell can also be detected in virions. To address whether the same is true for influenza virus, we used two complementary mass spectrometry approaches to perform a comprehensive proteomic analysis of purified influenza virus particles. In addition to the aforementioned nine virus-encoded proteins, we detected the presence of 36 host-encoded proteins. These include both cytoplasmic and membrane-bound proteins that can be grouped into several functional categories, such as cytoskeletal proteins, annexins, glycolytic enzymes, and tetraspanins. Interestingly, a significant number of these have also been reported to be present in virions of other virus families. Protease treatment of virions combined with immunoblot analysis was used to verify the presence of the cellular protein and also to determine whether it is located in the core of the influenza virus particle. Immunogold labeling confirmed the presence of membrane-bound host proteins on the influenza virus envelope. The identification of cellular constituents of influenza virions has important implications for understanding the interactions of influenza virus with its host and brings us a step closer to defining the cellular requirements for influenza virus replication. While not all of the host proteins are necessarily incorporated specifically, those that are and are found to have an essential role represent novel targets for antiviral drugs and for attenuation of viruses for vaccine purposes.",2008 Jun 6,"['Shaw, Megan L.', 'Stone, Kathryn L.', 'Colangelo, Christopher M.', 'Gulcicek, Erol E.', 'Palese, Peter']",PLoS Pathog,,,True
4cd8e92fcab8da2c840ff39f14ca35bf5ba6e444,PMC,Graphical presentation of diagnostic information,http://dx.doi.org/10.1186/1471-2288-8-20,PMC2394529,18405357,CC BY,"BACKGROUND: Graphical displays of results allow researchers to summarise and communicate the key findings of their study. Diagnostic information should be presented in an easily interpretable way, which conveys both test characteristics (diagnostic accuracy) and the potential for use in clinical practice (predictive value). METHODS: We discuss the types of graphical display commonly encountered in primary diagnostic accuracy studies and systematic reviews of such studies, and systematically review the use of graphical displays in recent diagnostic primary studies and systematic reviews. RESULTS: We identified 57 primary studies and 49 systematic reviews. Fifty-six percent of primary studies and 53% of systematic reviews used graphical displays to present results. Dot-plot or box-and- whisker plots were the most commonly used graph in primary studies and were included in 22 (39%) studies. ROC plots were the most common type of plot included in systematic reviews and were included in 22 (45%) reviews. One primary study and five systematic reviews included a probability-modifying plot. CONCLUSION: Graphical displays are currently underused in primary diagnostic accuracy studies and systematic reviews of such studies. Diagnostic accuracy studies need to include multiple types of graphic in order to provide both a detailed overview of the results (diagnostic accuracy) and to communicate information that can be used to inform clinical practice (predictive value). Work is required to improve graphical displays, to better communicate the utility of a test in clinical practice and the implications of test results for individual patients.",2008 Apr 11,"['Whiting, Penny F', 'Sterne, Jonathan AC', 'Westwood, Marie E', 'Bachmann, Lucas M', 'Harbord, Roger', 'Egger, Matthias', 'Deeks, Jonathan J']",BMC Med Res Methodol,,,True
b04df94d885c540b1a5adba12f6fb402e9a09b0c,PMC,Improved microarray gene expression profiling of virus-infected cells after removal of viral RNA,http://dx.doi.org/10.1186/1471-2164-9-221,PMC2397413,18479515,CC BY,"BACKGROUND: Sensitivity and accuracy are key points when using microarrays to detect alterations in gene expression under different conditions. Critical to the acquisition of reliable results is the preparation of the RNA. In the field of virology, when analyzing the host cell's reaction to infection, the often high representation of viral RNA (vRNA) within total RNA preparations from infected cells is likely to interfere with microarray analysis. Yet, this effect has not been investigated despite the many reports that describe gene expression profiling of virus-infected cells using microarrays. RESULTS: In this study we used coronaviruses as a model to show that vRNA indeed interferes with microarray analysis, decreasing both sensitivity and accuracy. We also demonstrate that the removal of vRNA from total RNA samples, by means of virus-specific oligonucleotide capturing, significantly reduced the number of false-positive hits and increased the sensitivity of the method as tested on different array platforms. CONCLUSION: We therefore recommend the specific removal of vRNA, or of any other abundant 'contaminating' RNAs, from total RNA samples to improve the quality and reliability of microarray analyses.",2008 May 14,"['Raaben, Matthijs', 'Whitley, Penn', 'Bouwmeester, Diane', 'Setterquist, Robert A', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,True
c36cd2c280cc73cdb747ef5c6058b3657859c767,PMC,Improved microarray gene expression profiling of virus-infected cells after removal of viral RNA,http://dx.doi.org/10.1186/1471-2164-9-221,PMC2397413,18479515,CC BY,"BACKGROUND: Sensitivity and accuracy are key points when using microarrays to detect alterations in gene expression under different conditions. Critical to the acquisition of reliable results is the preparation of the RNA. In the field of virology, when analyzing the host cell's reaction to infection, the often high representation of viral RNA (vRNA) within total RNA preparations from infected cells is likely to interfere with microarray analysis. Yet, this effect has not been investigated despite the many reports that describe gene expression profiling of virus-infected cells using microarrays. RESULTS: In this study we used coronaviruses as a model to show that vRNA indeed interferes with microarray analysis, decreasing both sensitivity and accuracy. We also demonstrate that the removal of vRNA from total RNA samples, by means of virus-specific oligonucleotide capturing, significantly reduced the number of false-positive hits and increased the sensitivity of the method as tested on different array platforms. CONCLUSION: We therefore recommend the specific removal of vRNA, or of any other abundant 'contaminating' RNAs, from total RNA samples to improve the quality and reliability of microarray analyses.",2008 May 14,"['Raaben, Matthijs', 'Whitley, Penn', 'Bouwmeester, Diane', 'Setterquist, Robert A', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,False
a6748cf5afbb792757eb09e822f8f2d49cd127b5,PMC,Improved microarray gene expression profiling of virus-infected cells after removal of viral RNA,http://dx.doi.org/10.1186/1471-2164-9-221,PMC2397413,18479515,CC BY,"BACKGROUND: Sensitivity and accuracy are key points when using microarrays to detect alterations in gene expression under different conditions. Critical to the acquisition of reliable results is the preparation of the RNA. In the field of virology, when analyzing the host cell's reaction to infection, the often high representation of viral RNA (vRNA) within total RNA preparations from infected cells is likely to interfere with microarray analysis. Yet, this effect has not been investigated despite the many reports that describe gene expression profiling of virus-infected cells using microarrays. RESULTS: In this study we used coronaviruses as a model to show that vRNA indeed interferes with microarray analysis, decreasing both sensitivity and accuracy. We also demonstrate that the removal of vRNA from total RNA samples, by means of virus-specific oligonucleotide capturing, significantly reduced the number of false-positive hits and increased the sensitivity of the method as tested on different array platforms. CONCLUSION: We therefore recommend the specific removal of vRNA, or of any other abundant 'contaminating' RNAs, from total RNA samples to improve the quality and reliability of microarray analyses.",2008 May 14,"['Raaben, Matthijs', 'Whitley, Penn', 'Bouwmeester, Diane', 'Setterquist, Robert A', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,False
4ace931a12cf4c36b131fcf16b49bf36eb15f8e3,PMC,Virus Adaptation by Manipulation of Host's Gene Expression,http://dx.doi.org/10.1371/journal.pone.0002397,PMC2398778,18545680,CC BY,"Viruses adapt to their hosts by evading defense mechanisms and taking over cellular metabolism for their own benefit. Alterations in cell metabolism as well as side-effects of antiviral responses contribute to symptoms development and virulence. Sometimes, a virus may spill over from its usual host species into a novel one, where usually will fail to successfully infect and further transmit to new host. However, in some cases, the virus transmits and persists after fixing beneficial mutations that allow for a better exploitation of the new host. This situation would represent a case for a new emerging virus. Here we report results from an evolution experiment in which a plant virus was allowed to infect and evolve on a naïve host. After 17 serial passages, the viral genome has accumulated only five changes, three of which were non-synonymous. An amino acid substitution in the viral VPg protein was responsible for the appearance of symptoms, whereas one substitution in the viral P3 protein the epistatically contributed to exacerbate severity. DNA microarray analyses show that the evolved and ancestral viruses affect the global patterns of host gene expression in radically different ways. A major difference is that genes involved in stress and pathogen response are not activated upon infection with the evolved virus, suggesting that selection has favored viral strategies to escape from host defenses.",2008 Jun 11,"['Agudelo-Romero, Patricia', 'Carbonell, Pablo', 'Perez-Amador, Miguel A.', 'Elena, Santiago F.']",PLoS One,,,True
566bdd537595b38dc6ab764b13d6d9ae33f9c9af,PMC,Mouse Hepatitis Coronavirus RNA Replication Depends on GBF1-Mediated ARF1 Activation,http://dx.doi.org/10.1371/journal.ppat.1000088,PMC2398782,18551169,CC BY,"Coronaviruses induce in infected cells the formation of double membrane vesicles, which are the sites of RNA replication. Not much is known about the formation of these vesicles, although recent observations indicate an important role for the endoplasmic reticulum in the formation of the mouse hepatitis coronavirus (MHV) replication complexes (RCs). We now show that MHV replication is sensitive to brefeldin A (BFA). Consistently, expression of a dominant-negative mutant of ARF1, known to mimic the action of the drug, inhibited MHV infection profoundly. Immunofluorescence analysis and quantitative electron microscopy demonstrated that BFA did not block the formation of RCs per se, but rather reduced their number. MHV RNA replication was not sensitive to BFA in MDCK cells, which are known to express the BFA-resistant guanine nucleotide exchange factor GBF1. Accordingly, individual knockdown of the Golgi-resident targets of BFA by transfection of small interfering RNAs (siRNAs) showed that GBF1, but not BIG1 or BIG2, was critically involved in MHV RNA replication. ARF1, the cellular effector of GBF1, also appeared to be involved in MHV replication, as siRNAs targeting this small GTPase inhibited MHV infection significantly. Collectively, our results demonstrate that GBF1-mediated ARF1 activation is required for efficient MHV RNA replication and reveal that the early secretory pathway and MHV replication complex formation are closely connected.",2008 Jun 13,"['Verheije, Monique H.', 'Raaben, Matthijs', 'Mari, Muriel', 'te Lintelo, Eddie G.', 'Reggiori, Fulvio', 'van Kuppeveld, Frank J. M.', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",PLoS Pathog,,,True
0132b8c2721692d9f53bd33a738fa94618bb4e91,PMC,Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays,http://dx.doi.org/10.1186/1471-2180-8-76,PMC2408589,18482458,CC BY,"BACKGROUND: Syphilis spirochete Treponema pallidum ssp. pallidum remains the enigmatic pathogen, since no virulence factors have been identified and the pathogenesis of the disease is poorly understood. Increasing rates of new syphilis cases per year have been observed recently. RESULTS: The genome of the SS14 strain was sequenced to high accuracy by an oligonucleotide array strategy requiring hybridization to only three arrays (Comparative Genome Sequencing, CGS). Gaps in the resulting sequence were filled with targeted dideoxy-terminators (DDT) sequencing and the sequence was confirmed by whole genome fingerprinting (WGF). When compared to the Nichols strain, 327 single nucleotide substitutions (224 transitions, 103 transversions), 14 deletions, and 18 insertions were found. On the proteome level, the highest frequency of amino acid-altering substitution polymorphisms was in novel genes, while the lowest was in housekeeping genes, as expected by their evolutionary conservation. Evidence was also found for hypervariable regions and multiple regions showing intrastrain heterogeneity in the T. pallidum chromosome. CONCLUSION: The observed genetic changes do not have influence on the ability of Treponema pallidum to cause syphilitic infection, since both SS14 and Nichols are virulent in rabbit. However, this is the first assessment of the degree of variation between the two syphilis pathogens and paves the way for phylogenetic studies of this fascinating organism.",2008 May 15,"['Matějková, Petra', 'Strouhal, Michal', 'Šmajs, David', 'Norris, Steven J', 'Palzkill, Timothy', 'Petrosino, Joseph F', 'Sodergren, Erica', 'Norton, Jason E', 'Singh, Jaz', 'Richmond, Todd A', 'Molla, Michael N', 'Albert, Thomas J', 'Weinstock, George M']",BMC Microbiol,,,True
0db939582f9ab5bb71581348ca000231d901c2f8,PMC,Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays,http://dx.doi.org/10.1186/1471-2180-8-76,PMC2408589,18482458,CC BY,"BACKGROUND: Syphilis spirochete Treponema pallidum ssp. pallidum remains the enigmatic pathogen, since no virulence factors have been identified and the pathogenesis of the disease is poorly understood. Increasing rates of new syphilis cases per year have been observed recently. RESULTS: The genome of the SS14 strain was sequenced to high accuracy by an oligonucleotide array strategy requiring hybridization to only three arrays (Comparative Genome Sequencing, CGS). Gaps in the resulting sequence were filled with targeted dideoxy-terminators (DDT) sequencing and the sequence was confirmed by whole genome fingerprinting (WGF). When compared to the Nichols strain, 327 single nucleotide substitutions (224 transitions, 103 transversions), 14 deletions, and 18 insertions were found. On the proteome level, the highest frequency of amino acid-altering substitution polymorphisms was in novel genes, while the lowest was in housekeeping genes, as expected by their evolutionary conservation. Evidence was also found for hypervariable regions and multiple regions showing intrastrain heterogeneity in the T. pallidum chromosome. CONCLUSION: The observed genetic changes do not have influence on the ability of Treponema pallidum to cause syphilitic infection, since both SS14 and Nichols are virulent in rabbit. However, this is the first assessment of the degree of variation between the two syphilis pathogens and paves the way for phylogenetic studies of this fascinating organism.",2008 May 15,"['Matějková, Petra', 'Strouhal, Michal', 'Šmajs, David', 'Norris, Steven J', 'Palzkill, Timothy', 'Petrosino, Joseph F', 'Sodergren, Erica', 'Norton, Jason E', 'Singh, Jaz', 'Richmond, Todd A', 'Molla, Michael N', 'Albert, Thomas J', 'Weinstock, George M']",BMC Microbiol,,,False
84a964d5dde5ffc12076b7c43ac5fff52210ad61,PMC,Comparative analysis of full genomic sequences among different genotypes of dengue virus type 3,http://dx.doi.org/10.1186/1743-422X-5-63,PMC2413216,18495043,CC BY,"BACKGROUND: Although the previous study demonstrated the envelope protein of dengue viruses is under purifying selection pressure, little is known about the genetic differences of full-length viral genomes of DENV-3. In our study, complete genomic sequencing of DENV-3 strains collected from different geographical locations and isolation years were determined and the sequence diversity as well as selection pressure sites in the DENV genome other than within the E gene were also analyzed. RESULTS: Using maximum likelihood and Bayesian approaches, our phylogenetic analysis revealed that the Taiwan's indigenous DENV-3 isolated from 1994 and 1998 dengue/DHF epidemics and one 1999 sporadic case were of the three different genotypes – I, II, and III, each associated with DENV-3 circulating in Indonesia, Thailand and Sri Lanka, respectively. Sequence diversity and selection pressure of different genomic regions among DENV-3 different genotypes was further examined to understand the global DENV-3 evolution. The highest nucleotide sequence diversity among the fully sequenced DENV-3 strains was found in the nonstructural protein 2A (mean ± SD: 5.84 ± 0.54) and envelope protein gene regions (mean ± SD: 5.04 ± 0.32). Further analysis found that positive selection pressure of DENV-3 may occur in the non-structural protein 1 gene region and the positive selection site was detected at position 178 of the NS1 gene. CONCLUSION: Our study confirmed that the envelope protein is under purifying selection pressure although it presented higher sequence diversity. The detection of positive selection pressure in the non-structural protein along genotype II indicated that DENV-3 originated from Southeast Asia needs to monitor the emergence of DENV strains with epidemic potential for better epidemic prevention and vaccine development.",2008 May 21,"['King, Chwan-Chuen', 'Chao, Day-Yu', 'Chien, Li-Jung', 'Chang, Gwong-Jen J', 'Lin, Ting-Hsiang', 'Wu, Yin-Chang', 'Huang, Jyh-Hsiung']",Virol J,,,True
86680d2981c3e641e014e777c8769031b89f933e,PMC,Healthcare workers' attitudes towards working during pandemic influenza: A multi method study,http://dx.doi.org/10.1186/1471-2458-8-192,PMC2423372,18518971,CC BY,"BACKGROUND: Healthcare workers (HCWs) will be key players in any response to pandemic influenza, and will be in the front line of exposure to infection. Responding effectively to a pandemic relies on the majority of medical, nursing, laboratory and hotel services staff continuing to work normally. Planning assumes that during a pandemic normal healthcare service levels will be provided, although it anticipates that as caseloads increase only essential care will be provided. The ability of the NHS to provide expected service levels is entirely dependent upon HCWs continuing to work as normal. METHODS/DESIGN: This study is designed as a two-phase multi-method study, incorporating focus groups and a questionnaire survey. In phase one, qualitative methods will be used to collect the views of a purposive sample of HCWs, to determine the range of factors associated with their responses to the prospect of working through pandemic influenza. In phase two, the findings from the focus groups, combined with the available literature, will be used to inform the design of a survey to determine the generalisability of these factors, enabling the estimation of the likely proportion of HCWs affected by each factor, and how likely it is that they would be willing and/or able to continue to work during an influenza pandemic. DISCUSSION: There are potentially greater than normal health risks for some healthcare workers working during a pandemic, and these workers may be concerned about infecting family members/friends. HCWs will be as liable as other workers to care for sick family members and friends. It is vital to have information about how motivated HCWs will be to continue to work during such a crisis, and what factors might influence their decision to work/not to work. Through the identification and subsequent management of these factors it may be possible to implement strategies that will alleviate the concerns and fears of HCWs and remove potential barriers to working.",2008 Jun 2,"['Draper, Heather', 'Wilson, Sue', 'Ives, Jonathan', 'Gratus, Christine', 'Greenfield, Sheila', 'Parry, Jayne', 'Petts, Judith', 'Sorell, Tom']",BMC Public Health,,,True
4873db67f7f48325e1c63ccfa093d5077a9c9b50,PMC,HyperISGylation of Old World Monkey ISG15 in Human Cells,http://dx.doi.org/10.1371/journal.pone.0002427,PMC2423471,18560560,CC BY,"BACKGROUND: ISG15 is an Ubiquitin-like protein, highly induced by Type I Interferons. Upon the cooperative activity of specific Ubiquitinating enzymes, ISG15 can be conjugated to its substrates. Increasing evidence points to a role for protein ISGylation in anti-viral and anti-tumoral defense. PRINCIPAL FINDINGS: We identified ISG15 from Old World Monkeys (OWm) as a hyper-efficient protein modifier. Western blot analysis visualized more efficient conjugation of OWmISG15 relative to HuISG15 in human (Hu), monkey and mouse (Mo) cell-lines. Moreover, the substrates of OWmISG15 identified upon Tandem Affinity Purification followed by LC-MS/MS identification largely outnumbered these of HuISG15 itself. Several Ubiquitin-Conjugating enzymes were identified as novel ISGylated substrates. Introduction of a N89D mutation in HuISG15 improved its ISGylation capacity, and additional Q31K/T33A/D133N mutations yielded a HuISG15 variant with an ISGylation efficiency comparable to OWmISG15. Homology modeling and structural superposition situate N89 in the interaction interface with the Activating enzyme. Analysis of the UbE1L residues in this interface revealed a striking homology between OWmUbE1L and HuUbE1, the Activating enzyme of Ubiquitin. In line with this observation, we found efficient activation of AgmISG15, but not HuISG15 or MoISG15, by HuUbE1, thus providing a likely explanation for OWm hyperISGylation. CONCLUSIONS: This study discloses the poor conjugation competence of HuISG15 compared to OWmISG15 and maps the critical determinants for efficient conjugation. HyperISGylation may greatly assist ISGylation studies and may enhance its function as positive regulator of Interferon-related immune responses or as anti-tumoral modulator.",2008 Jun 18,"['Pattyn, Els', 'Verhee, Annick', 'Uyttendaele, Isabel', 'Piessevaux, Julie', 'Timmerman, Evy', 'Gevaert, Kris', 'Vandekerckhove, Joël', 'Peelman, Frank', 'Tavernier, Jan']",PLoS One,,,True
976496c92ea74a516df11ebb445433f724e7f522,PMC,Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters,http://dx.doi.org/10.1186/1743-422X-5-69,PMC2426676,18519001,CC BY,"BACKGROUND: Human metapneumovirus (hMPV) infection can cause acute lower respiratory tract illness in infants, the immunocompromised, and the elderly. Currently there are no licensed preventative measures for hMPV infections. Using a variant of hMPV/NL/1/00 that does not require trypsin supplementation for growth in tissue culture, we deleted the M2-2 gene and evaluated the replication of rhMPV/ΔM2-2 virus in vitro and in vivo. RESULTS: In vitro studies showed that the ablation of M2-2 increased the propensity for insertion of U nucleotides in poly-U tracts of the genomic RNA. In addition, viral transcription was up-regulated although the level of genomic RNA remained comparable to rhMPV. Thus, deletion of M2-2 alters the ratio between hMPV genome copies and transcripts. In vivo, rhMPV/ΔM2-2 was attenuated compared to rhMPV in the lungs and nasal turbinates of hamsters. Hamsters immunized with one dose of rhMPV/ΔM2-2 were protected from challenge with 10(6 )PFU of wild type (wt) hMPV/NL/1/00. CONCLUSION: Our results suggest that hMPV M2-2 alters regulation of transcription and influences the fidelity of the polymerase complex during viral genome replication. In the hamster model, rhMPVΔM2-2 is attenuated and protective suggesting that deletion of M2-2 may result in a potential live vaccine candidate. A more thorough knowledge of the hMPV polymerase complex and the role of M2-2 during hMPV replication are being studied as we develop a potential live hMPV vaccine candidate that lacks M2-2 expression.",2008 Jun 3,"['Schickli, Jeanne H', 'Kaur, Jasmine', 'MacPhail, Mia', 'Guzzetta, Jeanne M', 'Spaete, Richard R', 'Tang, Roderick S']",Virol J,,,True
9e45efb86c7c552be221e4d1356d9374a7ebc204,PMC,Ubiquitination Is Required for Effective Replication of Coxsackievirus B3,http://dx.doi.org/10.1371/journal.pone.0002585,PMC2440516,18612413,CC BY,"BACKGROUND: Protein ubiquitination and/or degradation by the ubiquitin/proteasome system (UPS) have been recognized as critical mechanisms in the regulation of numerous essential cellular functions. The importance of the UPS in viral pathogenesis has become increasingly apparent. Using murine cardiomyocytes, we have previously demonstrated that the UPS plays a key role in the replication of coxsackievirus B3 (CVB3), an important human pathogen associated with various diseases. To further elucidate the underlying mechanisms, we examined the interplay between the UPS and CVB3, focusing on the role of ubiquitination in viral lifecycle. METHODOLOGY/PRINCIPAL FINDINGS: As assessed by in situ hybridization, Western blot, and plaque assay, we showed that proteasome inhibition decreased CVB3 RNA replication, protein synthesis, and viral titers in HeLa cells. There were no apparent changes in 20S proteasome activities following CVB3 infection. However, we found viral infection led to an accumulation of protein-ubiquitin conjugates, accompanied by a decreased protein expression of free ubiquitin, implicating an important role of ubiquitination in the UPS-mediated viral replication. Using small-interfering RNA, we demonstrated that gene-silencing of ubiquitin significantly reduced viral titers, possibly through downregulation of protein ubiquitination and subsequent alteration of protein function and/or degradation. Inhibition of deubiquitinating enzymes apparently enhances the inhibitory effects of proteasome inhibitors on CVB3 replication. Finally, by immunoprecipitation, we showed that coxsackieviral polymerase 3D was post-translationally modified by ubiquitination and such modification might be a prerequisite for its function in transcriptional regulation of viral genome. CONCLUSION: Coxsackievirus infection promotes protein ubiquitination, contributing to effective viral replication, probably through ubiquitin modification of viral polymerase.",2008 Jul 9,"['Si, Xiaoning', 'Gao, Guang', 'Wong, Jerry', 'Wang, Yahong', 'Zhang, Jingchun', 'Luo, Honglin']",PLoS One,,,True
6bfd7a2e092c039e792bae569c8406f2a47c2759,PMC,Professional and Home-Made Face Masks Reduce Exposure to Respiratory Infections among the General Population,http://dx.doi.org/10.1371/journal.pone.0002618,PMC2440799,18612429,CC BY,"BACKGROUND: Governments are preparing for a potential influenza pandemic. Therefore they need data to assess the possible impact of interventions. Face-masks worn by the general population could be an accessible and affordable intervention, if effective when worn under routine circumstances. METHODOLOGY: We assessed transmission reduction potential provided by personal respirators, surgical masks and home-made masks when worn during a variety of activities by healthy volunteers and a simulated patient. PRINCIPAL FINDINGS: All types of masks reduced aerosol exposure, relatively stable over time, unaffected by duration of wear or type of activity, but with a high degree of individual variation. Personal respirators were more efficient than surgical masks, which were more efficient than home-made masks. Regardless of mask type, children were less well protected. Outward protection (mask wearing by a mechanical head) was less effective than inward protection (mask wearing by healthy volunteers). CONCLUSIONS/SIGNIFICANCE: Any type of general mask use is likely to decrease viral exposure and infection risk on a population level, in spite of imperfect fit and imperfect adherence, personal respirators providing most protection. Masks worn by patients may not offer as great a degree of protection against aerosol transmission.",2008 Jul 9,"['van der Sande, Marianne', 'Teunis, Peter', 'Sabel, Rob']",PLoS One,,,True
0cd96fd42139b22b63e5752eda2c38990a18763a,PMC,Oct-4 Expression Maintained Cancer Stem-Like Properties in Lung Cancer-Derived CD133-Positive Cells,http://dx.doi.org/10.1371/journal.pone.0002637,PMC2440807,18612434,CC BY,"CD133 (prominin-1), a 5-transmembrane glycoprotein, has recently been considered to be an important marker that represents the subset population of cancer stem-like cells. Herein we report the isolation of CD133-positive cells (LC-CD133(+)) and CD133-negative cells (LC-CD133(−)) from tissue samples of ten patients with non-small cell lung cancer (LC) and five LC cell lines. LC-CD133(+) displayed higher Oct-4 expressions with the ability to self-renew and may represent a reservoir with proliferative potential for generating lung cancer cells. Furthermore, LC-CD133(+), unlike LC-CD133(−), highly co-expressed the multiple drug-resistant marker ABCG2 and showed significant resistance to chemotherapy agents (i.e., cisplatin, etoposide, doxorubicin, and paclitaxel) and radiotherapy. The treatment of Oct-4 siRNA with lentiviral vector can specifically block the capability of LC-CD133(+) to form spheres and can further facilitate LC-CD133(+) to differentiate into LC-CD133(−). In addition, knock-down of Oct-4 expression in LC-CD133(+) can significantly inhibit the abilities of tumor invasion and colony formation, and increase apoptotic activities of caspase 3 and poly (ADP-ribose) polymerase (PARP). Finally, in vitro and in vivo studies further confirm that the treatment effect of chemoradiotherapy for LC-CD133(+) can be improved by the treatment of Oct-4 siRNA. In conclusion, we demonstrated that Oct-4 expression plays a crucial role in maintaining the self-renewing, cancer stem-like, and chemoradioresistant properties of LC-CD133(+). Future research is warranted regarding the up-regulated expression of Oct-4 in LC-CD133(+) and malignant lung cancer.",2008 Jul 9,"['Chen, Yu-Chih', 'Hsu, Han-Shui', 'Chen, Yi-Wei', 'Tsai, Tung-Hu', 'How, Chorng-Kuang', 'Wang, Chien-Ying', 'Hung, Shih-Chieh', 'Chang, Yuh-Lih', 'Tsai, Ming-Long', 'Lee, Yi-Yen', 'Ku, Hung-Hai', 'Chiou, Shih-Hwa']",PLoS One,,,True
505d4036449010b44702841ae2564d6a55a3fbcd,PMC,Virus-Like Particles of SARS-Like Coronavirus Formed by Membrane Proteins from Different Origins Demonstrate Stimulating Activity in Human Dendritic Cells,http://dx.doi.org/10.1371/journal.pone.0002685,PMC2441860,18628832,CC BY,"The pathogenesis of SARS coronavirus (CoV) remains poorly understood. In the current study, two recombinant baculovirus were generated to express the spike (S) protein of SARS-like coronavirus (SL-CoV) isolated from bats (vAcBS) and the envelope (E) and membrane (M) proteins of SARS-CoV, respectively. Co-infection of insect cells with these two recombinant baculoviruses led to self-assembly of virus-like particles (BVLPs) as demonstrated by electron microscopy. Incorporation of S protein of vAcBS (BS) into VLPs was confirmed by western blot and immunogold labeling. Such BVLPs up-regulated the level of CD40, CD80, CD86, CD83, and enhanced the secretion of IL-6, IL-10 and TNF-α in immature dendritic cells (DCs). Immune responses were compared in immature DCs inoculated with BVLPs or with VLPs formed by S, E and M proteins of human SARS-CoV. BVLPs showed a stronger ability to stimulate DCs in terms of cytokine induction as evidenced by 2 to 6 fold higher production of IL-6 and TNF-α. Further study indicated that IFN-γ+ and IL-4+ populations in CD4+ T cells increased upon co-cultivation with DCs pre-exposed with BVLPs or SARS-CoV VLPs. The observed difference in DC-stimulating activity between BVLPs and SARS CoV VLPs was very likely due to the S protein. In agreement, SL-CoV S DNA vaccine evoked a more vigorous antibody response and a stronger T cell response than SARS-CoV S DNA in mice. Our data have demonstrated for the first time that SL-CoV VLPs formed by membrane proteins of different origins, one from SL-CoV isolated from bats (BS) and the other two from human SARS-CoV (E and M), activated immature DCs and enhanced the expression of co-stimulatory molecules and the secretion of cytokines. Finding in this study may provide important information for vaccine development as well as for understanding the pathogenesis of SARS-like CoV.",2008 Jul 16,"['Bai, Bingke', 'Hu, Qinxue', 'Hu, Hui', 'Zhou, Peng', 'Shi, Zhengli', 'Meng, Jin', 'Lu, Baojing', 'Huang, Yi', 'Mao, Panyong', 'Wang, Hanzhong']",PLoS One,,,True
1b7c700ee3a33c0a675a5f7e71a20ce62467b900,PMC,Expression of HIV-1 antigens in plants as potential subunit vaccines,http://dx.doi.org/10.1186/1472-6750-8-53,PMC2443125,18573204,CC BY,"BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) has infected more than 40 million people worldwide, mainly in sub-Saharan Africa. The high prevalence of HIV-1 subtype C in southern Africa necessitates the development of cheap, effective vaccines. One means of production is the use of plants, for which a number of different techniques have been successfully developed. HIV-1 Pr55Gag is a promising HIV-1 vaccine candidate: we compared the expression of this and a truncated Gag (p17/p24) and the p24 capsid subunit in Nicotiana spp. using transgenic plants and transient expression via Agrobacterium tumefaciens and recombinant tobamovirus vectors. We also investigated the influence of subcellular localisation of recombinant protein to the chloroplast and the endoplasmic reticulum (ER) on protein yield. We partially purified a selected vaccine candidate and tested its stimulation of a humoral and cellular immune response in mice. RESULTS: Both transient and transgenic expression of the HIV antigens were successful, although expression of Pr55Gag was low in all systems; however, the Agrobacterium-mediated transient expression of p24 and p17/p24 yielded best, to more than 1 mg p24/kg fresh weight. Chloroplast targeted protein levels were highest in transient and transgenic expression of p24 and p17/p24. The transiently-expressed p17/p24 was not immunogenic in mice as a homologous vaccine, but it significantly boosted a humoral and T cell immune response primed by a gag DNA vaccine, pTHGagC. CONCLUSION: Transient agroinfiltration was best for expression of all of the recombinant proteins tested, and p24 and p17/p24 were expressed at much higher levels than Pr55Gag. Our results highlight the usefulness of plastid signal peptides in enhancing the production of recombinant proteins meant for use as vaccines. The p17/p24 protein effectively boosted T cell and humoral responses in mice primed by the DNA vaccine pTHGagC, showing that this plant-produced protein has potential for use as a vaccine.",2008 Jun 23,"['Meyers, Ann', 'Chakauya, Ereck', 'Shephard, Enid', 'Tanzer, Fiona L', 'Maclean, James', 'Lynch, Alisson', 'Williamson, Anna-Lise', 'Rybicki, Edward P']",BMC Biotechnol,,,True
77138f50684f6b8c48752afd24cbb63abaad4aa4,PMC,"Gatekeepers of health: A qualitative assessment of child care centre staff's perspectives, practices and challenges to enteric illness prevention and management in child care centres",http://dx.doi.org/10.1186/1471-2458-8-212,PMC2443801,18554408,CC BY,"BACKGROUND: Enteric outbreaks associated with child care centres (CCC) have been well documented internationally and in Canada. The current literature focuses on identifying potential risk factors for introduction and transmission of enteric disease, but does not examine why these risk factors happen, how the risk is understood and managed by the staff of CCCs, or what challenges they experience responding to enteric illness. The purpose of this study was to explore the understanding, knowledge and actions of CCC staff regarding enteric illness and outbreaks, and to identify challenges that staff encounter while managing them. METHODS: Focus groups were conducted with staff of regulated CCCs in Southern Ontario. Five focus groups were held with 40 participants. An open ended style of interviewing was used. Data were analyzed using content analysis. RESULTS: CCC staff play an important role in preventing and managing enteric illness. Staff used in-depth knowledge of the children, the centre and their personal experiences to assist in making decisions related to enteric illness. The decisions and actions may differ from guidance provided by public health officials, particularly when faced with challenges related to time, money, staffing and parents. CONCLUSION: CCC staff relied on experience and judgment in coordination with public health information to assist decision-making in the management of enteric illness and outbreaks. Advice and guidance from public health officials to CCC staff needs to be consistent yet flexible so that it may be adapted in a variety of situations and meet regulatory and public health requirements.",2008 Jun 13,"['Taylor, Marsha', 'Adams, Cindy L', 'Ellis, Andrea']",BMC Public Health,,,True
341a9a57e865081e81a9c60b97802773761ce8c4,PMC,Dating the time of viral subtype divergence,http://dx.doi.org/10.1186/1471-2148-8-172,PMC2443812,18541033,CC BY,"Precise dating of viral subtype divergence enables researchers to correlate divergence with geographic and demographic occurrences. When historical data are absent (that is, the overwhelming majority), viral sequence sampling on a time scale commensurate with the rate of substitution permits the inference of the times of subtype divergence. Currently, researchers use two strategies to approach this task, both requiring strong conditions on the molecular clock assumption of substitution rate. As the underlying structure of the substitution rate process at the time of subtype divergence is not understood and likely highly variable, we present a simple method that estimates rates of substitution, and from there, times of divergence, without use of an assumed molecular clock. We accomplish this by blending estimates of the substitution rate for triplets of dated sequences where each sequence draws from a distinct viral subtype, providing a zeroth-order approximation for the rate between subtypes. As an example, we calculate the time of divergence for three genes among influenza subtypes A-H3N2 and B using subtype C as an outgroup. We show a time of divergence approximately 100 years ago, substantially more recent than previous estimates which range from 250 to 3800 years ago.",2008 Jun 9,"[""O'Brien, John D"", 'She, Zhen-Su', 'Suchard, Marc A']",BMC Evol Biol,,,True
d73eaecdf6e03c65d962791c98563c8a7d5cf79a,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.60,PMC2447222,,CC BY,,2001 Dec,,Comp Funct Genomics,,,True
17d0d25ab7105e239f9d13e41489d01d9a40c34a,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.231,PMC2447311,,CC BY,,2003 Dec,,Comp Funct Genomics,,,True
692bdad285cb5d0d0f00e949bb323fc13cc56750,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.350,PMC2447323,,CC BY,,2004 Feb,,Comp Funct Genomics,,,False
d9f0fd49a89212c8d2089c84cd9a9d8573277288,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.355,PMC2447430,,CC BY,,2004 Aug-Oct,,Comp Funct Genomics,,,True
f670f4bb6f79e54d7603f8520853b1f0d105b588,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.353,PMC2447453,,CC BY,,2004 Jun,,Comp Funct Genomics,,,True
bc403b497ddc13f1a5352d7eef9d0fdaeccbc028,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.357,PMC2447475,,CC BY,,2004 Dec,,Comp Funct Genomics,,,True
cfacb72c36e1bb7fade469d8bf5ebc12143e0b3e,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.421,PMC2447482,,CC BY,,2005 Jun,,Comp Funct Genomics,,,True
e8b3d7f86dd48b422693465d39ce72280df5527c,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.425,PMC2447491,,CC BY,,2005 Oct-Dec,,Comp Funct Genomics,,,True
cef34a0d6cfce0c84ac90fb01338bb2429693d9e,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.422,PMC2447508,,CC BY,,2005 Jul-Aug,,Comp Funct Genomics,,,True
2eb279d1dfd4b3649ed0ff00c4e5a72261d445a0,PMC,Current Awareness on Comparative and Functional Genomics,http://dx.doi.org/10.1002/cfg.419,PMC2448604,,CC BY,,2005 Feb-Mar,,Comp Funct Genomics,,,True
023dff96542ca1e77e3a1d08a2f3893ca1ebc057,PMC,"Sequences, Annotation and Single Nucleotide Polymorphism of the Major Histocompatibility Complex in the Domestic Cat",http://dx.doi.org/10.1371/journal.pone.0002674,PMC2453318,18629345,CC0,"Two sequences of major histocompatibility complex (MHC) regions in the domestic cat, 2.976 and 0.362 Mbps, which were separated by an ancient chromosome break (55–80 MYA) and followed by a chromosomal inversion were annotated in detail. Gene annotation of this MHC was completed and identified 183 possible coding regions, 147 human homologues, possible functional genes and 36 pseudo/unidentified genes) by GENSCAN and BLASTN, BLASTP RepeatMasker programs. The first region spans 2.976 Mbp sequence, which encodes six classical class II antigens (three DRA and three DRB antigens) lacking the functional DP, DQ regions, nine antigen processing molecules (DOA/DOB, DMA/DMB, TAPASIN, and LMP2/LMP7,TAP1/TAP2), 52 class III genes, nineteen class I genes/gene fragments (FLAI-A to FLAI-S). Three class I genes (FLAI-H, I-K, I-E) may encode functional classical class I antigens based on deduced amino acid sequence and promoter structure. The second region spans 0.362 Mbp sequence encoding no class I genes and 18 cross-species conserved genes, excluding class I, II and their functionally related/associated genes, namely framework genes, including three olfactory receptor genes. One previously identified feline endogenous retrovirus, a baboon retrovirus derived sequence (ECE1) and two new endogenous retrovirus sequences, similar to brown bat endogenous retrovirus (FERVmlu1, FERVmlu2) were found within a 140 Kbp interval in the middle of class I region. MHC SNPs were examined based on comparisons of this BAC sequence and MHC homozygous 1.9× WGS sequences and found that 11,654 SNPs in 2.84 Mbp (0.00411 SNP per bp), which is 2.4 times higher rate than average heterozygous region in the WGS (0.0017 SNP per bp genome), and slightly higher than the SNP rate observed in human MHC (0.00337 SNP per bp).",2008 Jul 16,"['Yuhki, Naoya', 'Mullikin, James C.', 'Beck, Thomas', 'Stephens, Robert', ""O'Brien, Stephen J.""]",PLoS One,,,True
103c89c60d7d24bb8432c4b7a61379f9e44fe6ea,PMC,Does Pathogen Spillover from Commercially Reared Bumble Bees Threaten Wild Pollinators?,http://dx.doi.org/10.1371/journal.pone.0002771,PMC2464710,18648661,CC BY,"The conservation of insect pollinators is drawing attention because of reported declines in bee species and the ‘ecosystem services’ they provide. This issue has been brought to a head by recent devastating losses of honey bees throughout North America (so called, ‘Colony Collapse Disorder’); yet, we still have little understanding of the cause(s) of bee declines. Wild bumble bees (Bombus spp.) have also suffered serious declines and circumstantial evidence suggests that pathogen ‘spillover’ from commercially reared bumble bees, which are used extensively to pollinate greenhouse crops, is a possible cause. We constructed a spatially explicit model of pathogen spillover in bumble bees and, using laboratory experiments and the literature, estimated parameter values for the spillover of Crithidia bombi, a destructive pathogen commonly found in commercial Bombus. We also monitored wild bumble bee populations near greenhouses for evidence of pathogen spillover, and compared the fit of our model to patterns of C. bombi infection observed in the field. Our model predicts that, during the first three months of spillover, transmission from commercial hives would infect up to 20% of wild bumble bees within 2 km of the greenhouse. However, a travelling wave of disease is predicted to form suddenly, infecting up to 35–100% of wild Bombus, and spread away from the greenhouse at a rate of 2 km/wk. In the field, although we did not observe a large epizootic wave of infection, the prevalences of C. bombi near greenhouses were consistent with our model. Indeed, we found that spillover has allowed C. bombi to invade several wild bumble bee species near greenhouses. Given the available evidence, it is likely that pathogen spillover from commercial bees is contributing to the ongoing decline of wild Bombus in North America. Improved management of domestic bees, for example by reducing their parasite loads and their overlap with wild congeners, could diminish or even eliminate pathogen spillover.",2008 Jul 23,"['Otterstatter, Michael C.', 'Thomson, James D.']",PLoS One,,,True
78b008cc190700f5c0291d67cca3112f6b54aa1f,PMC,Temporal trends in the discovery of human viruses,http://dx.doi.org/10.1098/rspb.2008.0294,PMC2475551,18505720,CC BY,"On average, more than two new species of human virus are reported every year. We constructed the cumulative species discovery curve for human viruses going back to 1901. We fitted a statistical model to these data; the shape of the curve strongly suggests that the process of virus discovery is far from complete. We generated a 95% credible interval for the pool of as yet undiscovered virus species of 38–562. We extrapolated the curve and generated an estimate of 10–40 new species to be discovered by 2020. Although we cannot predict the level of health threat that these new viruses will present, we conclude that novel virus species must be anticipated in public health planning. More systematic virus discovery programmes, covering both humans and potential animal reservoirs of human viruses, should be considered.",2008 Sep 22,"['Woolhouse, Mark E.J', 'Howey, Richard', 'Gaunt, Eleanor', 'Reilly, Liam', 'Chase-Topping, Margo', 'Savill, Nick']",Proc Biol Sci,,,True
72f9a628e9d59676c5cbed4485e64c5757a4c78a,PMC,Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006),http://dx.doi.org/10.1371/journal.pone.0002768,PMC2481298,18648550,CC BY,"BACKGROUND: The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997–2006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations. CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.",2008 Jul 23,"['Tang, Julian W.', 'Ngai, Karry L. K.', 'Lam, Wai Y.', 'Chan, Paul K. S.']",PLoS One,,,True
6cd550c5672e5101c0047c22993ec1466e3ac185,PMC,Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006),http://dx.doi.org/10.1371/journal.pone.0002768,PMC2481298,18648550,CC BY,"BACKGROUND: The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997–2006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations. CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.",2008 Jul 23,"['Tang, Julian W.', 'Ngai, Karry L. K.', 'Lam, Wai Y.', 'Chan, Paul K. S.']",PLoS One,,,False
d1d195d19219b396b2cf7dcaf3e3911aa3d6c516,PMC,Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006),http://dx.doi.org/10.1371/journal.pone.0002768,PMC2481298,18648550,CC BY,"BACKGROUND: The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997–2006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations. CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.",2008 Jul 23,"['Tang, Julian W.', 'Ngai, Karry L. K.', 'Lam, Wai Y.', 'Chan, Paul K. S.']",PLoS One,,,False
8467a3df4f6a9a8e33efd8134bc13394c70c6740,PMC,Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006),http://dx.doi.org/10.1371/journal.pone.0002768,PMC2481298,18648550,CC BY,"BACKGROUND: The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997–2006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations. CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.",2008 Jul 23,"['Tang, Julian W.', 'Ngai, Karry L. K.', 'Lam, Wai Y.', 'Chan, Paul K. S.']",PLoS One,,,False
596e771e860af036be53a0f54e56d815348c329c,PMC,Seasonality of Influenza A(H3N2) Virus: A Hong Kong Perspective (1997–2006),http://dx.doi.org/10.1371/journal.pone.0002768,PMC2481298,18648550,CC BY,"BACKGROUND: The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: 281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997–2006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations. CONCLUSIONS/SIGNIFICANCE: The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.",2008 Jul 23,"['Tang, Julian W.', 'Ngai, Karry L. K.', 'Lam, Wai Y.', 'Chan, Paul K. S.']",PLoS One,,,False
1e2989b7156dc944d0a24b596fd17aaa08b3b56c,PMC,A phase 1 trial of nebulised heparin in acute lung injury,http://dx.doi.org/10.1186/cc6894,PMC2481447,18460218,CC BY,"INTRODUCTION: Animal studies of acute lung injury (ALI) suggest nebulised heparin may limit damage from fibrin deposition in the alveolar space and microcirculation. No human studies have been undertaken to date. We assessed the feasibility, safety and potential anticoagulant effects of administration of nebulised heparin to patients with ALI. METHODS: An open label phase 1 trial of four escalating doses of nebulised heparin was performed. A total of 16 ventilated patients with ALI were studied. The first group was administered a total of 50,000 U/day, the second group 100,000 U/day, the third group 200,000 U/day and the fourth group 400,000 U/day. Assessments of lung function included the PaO(2)/FiO(2 )ratio, lung compliance and the alveolar dead space fraction. Monitoring of anticoagulation included the activated partial thromboplastin time (APTT) and the thrombin clotting time. Bronchoalveolar lavage fluid was collected and the prothrombin fragment and tissue plasminogen activator levels were assessed. Analysis of variance was used to compare the effects of dose. RESULTS: No serious adverse events occurred for any dose. The changes over time for the PaO(2)/FiO(2 )ratio, lung compliance and the alveolar dead space fraction levels were similar for all doses. A trend to increased APTT and thrombin clotting time levels was present with higher doses (P = 0.09 and P = 0.1, respectively). For the highest dose, the APTT reached 64 seconds; following cessation of nebulised heparin, the APTT fell to 39 seconds (P = 0.06). In bronchoalveolar lavage samples a trend to reduced prothrombin fragment levels was present with higher doses (P = 0.1), while tissue plasminogen activator levels were similar for all doses. CONCLUSION: Administration of nebulised heparin to mechanically ventilated patients with ALI is feasible. Nebulised heparin was not associated with any serious adverse events, and at higher doses it increased APTT levels. Larger trials are required to further investigate the safety and efficacy of nebulised heparin. In these trials due consideration must be given to systemic anticoagulant effects. TRIAL REGISTRATION: Australian Clinical trials registry ACTRN12606000388516.",2008 May 6,"['Dixon, Barry', 'Santamaria, John D', 'Campbell, Duncan J']",Crit Care,,,True
6ed1c5f102cce4bbcbd9d5438b6b8be3d4746484,PMC,H5N1 and 1918 Pandemic Influenza Virus Infection Results in Early and Excessive Infiltration of Macrophages and Neutrophils in the Lungs of Mice,http://dx.doi.org/10.1371/journal.ppat.1000115,PMC2483250,18670648,CC0,"Fatal human respiratory disease associated with the 1918 pandemic influenza virus and potentially pandemic H5N1 viruses is characterized by severe lung pathology, including pulmonary edema and extensive inflammatory infiltrate. Here, we quantified the cellular immune response to infection in the mouse lung by flow cytometry and demonstrate that mice infected with highly pathogenic (HP) H1N1 and H5N1 influenza viruses exhibit significantly high numbers of macrophages and neutrophils in the lungs compared to mice infected with low pathogenic (LP) viruses. Mice infected with the 1918 pandemic virus and a recent H5N1 human isolate show considerable similarities in overall lung cellularity, lung immune cell sub-population composition and cellular immune temporal dynamics. Interestingly, while these similarities were observed, the HP H5N1 virus consistently elicited significantly higher levels of pro-inflammatory cytokines in whole lungs and primary human macrophages, revealing a potentially critical difference in the pathogenesis of H5N1 infections. These results together show that infection with HP influenza viruses such as H5N1 and the 1918 pandemic virus leads to a rapid cell recruitment of macrophages and neutrophils into the lungs, suggesting that these cells play a role in acute lung inflammation associated with HP influenza virus infection. In addition, primary macrophages and dendritic cells were also susceptible to 1918 and H5N1 influenza virus infection in vitro and in infected mouse lung tissue.",2008 Aug 1,"['Perrone, Lucy A.', 'Plowden, Julie K.', 'García-Sastre, Adolfo', 'Katz, Jacqueline M.', 'Tumpey, Terrence M.']",PLoS Pathog,,,True
17b8edaf62be1b907bf750a94c4b881f3db1f7be,PMC,Gene silencing by RNAi in mouse Sertoli cells,http://dx.doi.org/10.1186/1477-7827-6-29,PMC2483279,18620581,CC BY,"BACKGROUND: RNA interference (RNAi) is a valuable tool in the investigation of gene function. The purpose of this study was to examine the availability, target cell types and efficiency of RNAi in the mouse seminiferous epithelium. METHODS: The experimental model was based on transgenic mice expressing EGFP (enhanced green fluorescent protein). RNAi was induced by in vivo transfection of plasmid vectors encoding for short hairpin RNAs (shRNAs) targeting EGFP. shRNAs were transfected in vivo by microinjection into the seminiferous tubules via the rete testis followed by square wave electroporation. As a transfection reporter, expression of red fluorescent protein (HcRed 1) was used. Cell types, the efficiency of both transfections and RNAi were all evaluated. RESULTS: Sertoli cells were the main transfected cells. A reduction of about 40% in the level of EGFP protein was detected in cells successfully transfected both in vivo and in vitro. However, the efficiency of in vivo transfection was low. CONCLUSION: In adult seminiferous epithelial cells, in vivo post-transcriptional gene silencing mediated by RNAi via shRNA is efficient in Sertoli cells. Similar levels of RNAi were detected both in vivo and in vitro. This also indicates that Sertoli cells have the necessary silencing machinery to repress the expression of endogenous genes via RNAi.",2008 Jul 11,"['González-González, Emilio', 'López-Casas, Pedro P', 'del Mazo, Jesús']",Reprod Biol Endocrinol,,,True
01c6c44650ad5466cdb134a28d0b14700fa3906d,PMC,Patterns of Positive Selection in Six Mammalian Genomes,http://dx.doi.org/10.1371/journal.pgen.1000144,PMC2483296,18670650,CC BY,"Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small numbers of available genomes. Here we present the most comprehensive examination of mammalian PSGs to date, using the six high-coverage genome assemblies now available for eutherian mammals. The increased phylogenetic depth of this dataset results in substantially improved statistical power, and permits several new lineage- and clade-specific tests to be applied. Of ∼16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR<0.05), according to a standard likelihood ratio test. An additional 144 genes showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity and taste perception. Several pathways were strongly enriched for PSGs, suggesting possible co-evolution of interacting genes. A novel Bayesian analysis of the possible “selection histories” of each gene indicated that most PSGs have switched multiple times between positive selection and nonselection, suggesting that positive selection is often episodic. A detailed analysis of Affymetrix exon array data indicated that PSGs are expressed at significantly lower levels, and in a more tissue-specific manner, than non-PSGs. Genes that are specifically expressed in the spleen, testes, liver, and breast are significantly enriched for PSGs, but no evidence was found for an enrichment for PSGs among brain-specific genes. This study provides additional evidence for widespread positive selection in mammalian evolution and new genome-wide insights into the functional implications of positive selection.",2008 Aug 1,"['Kosiol, Carolin', 'Vinař, Tomáš', 'da Fonseca, Rute R.', 'Hubisz, Melissa J.', 'Bustamante, Carlos D.', 'Nielsen, Rasmus', 'Siepel, Adam']",PLoS Genet,,,True
ac7dab707a31d84f05dbc9136dba4cf3770183dd,PMC,Patterns of Positive Selection in Six Mammalian Genomes,http://dx.doi.org/10.1371/journal.pgen.1000144,PMC2483296,18670650,CC BY,"Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small numbers of available genomes. Here we present the most comprehensive examination of mammalian PSGs to date, using the six high-coverage genome assemblies now available for eutherian mammals. The increased phylogenetic depth of this dataset results in substantially improved statistical power, and permits several new lineage- and clade-specific tests to be applied. Of ∼16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR<0.05), according to a standard likelihood ratio test. An additional 144 genes showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity and taste perception. Several pathways were strongly enriched for PSGs, suggesting possible co-evolution of interacting genes. A novel Bayesian analysis of the possible “selection histories” of each gene indicated that most PSGs have switched multiple times between positive selection and nonselection, suggesting that positive selection is often episodic. A detailed analysis of Affymetrix exon array data indicated that PSGs are expressed at significantly lower levels, and in a more tissue-specific manner, than non-PSGs. Genes that are specifically expressed in the spleen, testes, liver, and breast are significantly enriched for PSGs, but no evidence was found for an enrichment for PSGs among brain-specific genes. This study provides additional evidence for widespread positive selection in mammalian evolution and new genome-wide insights into the functional implications of positive selection.",2008 Aug 1,"['Kosiol, Carolin', 'Vinař, Tomáš', 'da Fonseca, Rute R.', 'Hubisz, Melissa J.', 'Bustamante, Carlos D.', 'Nielsen, Rasmus', 'Siepel, Adam']",PLoS Genet,,,False
63e7c7d005ecaf98cbd7daa6bdbe66998c4c4322,PMC,Patterns of Positive Selection in Six Mammalian Genomes,http://dx.doi.org/10.1371/journal.pgen.1000144,PMC2483296,18670650,CC BY,"Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small numbers of available genomes. Here we present the most comprehensive examination of mammalian PSGs to date, using the six high-coverage genome assemblies now available for eutherian mammals. The increased phylogenetic depth of this dataset results in substantially improved statistical power, and permits several new lineage- and clade-specific tests to be applied. Of ∼16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR<0.05), according to a standard likelihood ratio test. An additional 144 genes showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity and taste perception. Several pathways were strongly enriched for PSGs, suggesting possible co-evolution of interacting genes. A novel Bayesian analysis of the possible “selection histories” of each gene indicated that most PSGs have switched multiple times between positive selection and nonselection, suggesting that positive selection is often episodic. A detailed analysis of Affymetrix exon array data indicated that PSGs are expressed at significantly lower levels, and in a more tissue-specific manner, than non-PSGs. Genes that are specifically expressed in the spleen, testes, liver, and breast are significantly enriched for PSGs, but no evidence was found for an enrichment for PSGs among brain-specific genes. This study provides additional evidence for widespread positive selection in mammalian evolution and new genome-wide insights into the functional implications of positive selection.",2008 Aug 1,"['Kosiol, Carolin', 'Vinař, Tomáš', 'da Fonseca, Rute R.', 'Hubisz, Melissa J.', 'Bustamante, Carlos D.', 'Nielsen, Rasmus', 'Siepel, Adam']",PLoS Genet,,,False
9bc181d540a6368fb97eaa7cf4e0f852c22e7826,PMC,Patterns of Positive Selection in Six Mammalian Genomes,http://dx.doi.org/10.1371/journal.pgen.1000144,PMC2483296,18670650,CC BY,"Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small numbers of available genomes. Here we present the most comprehensive examination of mammalian PSGs to date, using the six high-coverage genome assemblies now available for eutherian mammals. The increased phylogenetic depth of this dataset results in substantially improved statistical power, and permits several new lineage- and clade-specific tests to be applied. Of ∼16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR<0.05), according to a standard likelihood ratio test. An additional 144 genes showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity and taste perception. Several pathways were strongly enriched for PSGs, suggesting possible co-evolution of interacting genes. A novel Bayesian analysis of the possible “selection histories” of each gene indicated that most PSGs have switched multiple times between positive selection and nonselection, suggesting that positive selection is often episodic. A detailed analysis of Affymetrix exon array data indicated that PSGs are expressed at significantly lower levels, and in a more tissue-specific manner, than non-PSGs. Genes that are specifically expressed in the spleen, testes, liver, and breast are significantly enriched for PSGs, but no evidence was found for an enrichment for PSGs among brain-specific genes. This study provides additional evidence for widespread positive selection in mammalian evolution and new genome-wide insights into the functional implications of positive selection.",2008 Aug 1,"['Kosiol, Carolin', 'Vinař, Tomáš', 'da Fonseca, Rute R.', 'Hubisz, Melissa J.', 'Bustamante, Carlos D.', 'Nielsen, Rasmus', 'Siepel, Adam']",PLoS Genet,,,False
c86eba5cb05531b033922afbe3f9148d1cd3c5dc,PMC,Patterns of Positive Selection in Six Mammalian Genomes,http://dx.doi.org/10.1371/journal.pgen.1000144,PMC2483296,18670650,CC BY,"Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small numbers of available genomes. Here we present the most comprehensive examination of mammalian PSGs to date, using the six high-coverage genome assemblies now available for eutherian mammals. The increased phylogenetic depth of this dataset results in substantially improved statistical power, and permits several new lineage- and clade-specific tests to be applied. Of ∼16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR<0.05), according to a standard likelihood ratio test. An additional 144 genes showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity and taste perception. Several pathways were strongly enriched for PSGs, suggesting possible co-evolution of interacting genes. A novel Bayesian analysis of the possible “selection histories” of each gene indicated that most PSGs have switched multiple times between positive selection and nonselection, suggesting that positive selection is often episodic. A detailed analysis of Affymetrix exon array data indicated that PSGs are expressed at significantly lower levels, and in a more tissue-specific manner, than non-PSGs. Genes that are specifically expressed in the spleen, testes, liver, and breast are significantly enriched for PSGs, but no evidence was found for an enrichment for PSGs among brain-specific genes. This study provides additional evidence for widespread positive selection in mammalian evolution and new genome-wide insights into the functional implications of positive selection.",2008 Aug 1,"['Kosiol, Carolin', 'Vinař, Tomáš', 'da Fonseca, Rute R.', 'Hubisz, Melissa J.', 'Bustamante, Carlos D.', 'Nielsen, Rasmus', 'Siepel, Adam']",PLoS Genet,,,True
9d08aa9bb599cb599ceaa62f31cb480a5708a5d1,PMC,Delayed Treatment of Diagnosed Pulmonary Tuberculosis in Taiwan,http://dx.doi.org/10.1186/1471-2458-8-236,PMC2483710,18620595,CC BY,"BACKGROUND: Mycobacterium tuberculosis infection is an ongoing public health problem in Taiwan. The National Tuberculosis Registry Campaign, a case management system, was implemented in 1997. This study examined this monitoring system to identify and characterize delayed treatment of TB patients. METHODS: Records of all tuberculosis cases treated in Taiwan from 2002 through 2005 were obtained from the National Tuberculosis Registry Campaign. Initiation of treatment more than 7 days after diagnosis was considered a long treatment delay. RESULTS: The study included 31,937 patients. The mean day of delayed treatment was 3.6 days. Most patients were treated immediately after diagnosis. The relationship between number of TB patients and days of delayed treatment after diagnosis exhibited a Power-law distribution. The long tail of the power-law distribution indicated that an extreme number occur cannot be neglected. Tuberculosis patients treated after an unusually long delay require close observation and follow up. CONCLUSION: This study found that TB control is generally acceptabl in Taiwan; however, delayed treatment increases the risk of transmission. Improving the protocol for managing confirmed TB cases can minimize disease transmission.",2008 Jul 13,"['Chern, Jimmy PS', 'Chen, Duan-Rung', 'Wen, Tzai-Hung']",BMC Public Health,,,True
3fbbb5c2047570f4c33a88cb927a6f54e83de658,PMC,Mathematical Analysis of Copy Number Variation in a DNA Sample Using Digital PCR on a Nanofluidic Device,http://dx.doi.org/10.1371/journal.pone.0002876,PMC2483940,18682853,CC BY,"Copy Number Variations (CNVs) of regions of the human genome have been associated with multiple diseases. We present an algorithm which is mathematically sound and computationally efficient to accurately analyze CNV in a DNA sample utilizing a nanofluidic device, known as the digital array. This numerical algorithm is utilized to compute copy number variation and the associated statistical confidence interval and is based on results from probability theory and statistics. We also provide formulas which can be used as close approximations.",2008 Aug 6,"['Dube, Simant', 'Qin, Jian', 'Ramakrishnan, Ramesh']",PLoS One,,,True
176274e5fb44083ebc8c91d87e013d624533c7f6,PMC,Conservation and Variability of Dengue Virus Proteins: Implications for Vaccine Design,http://dx.doi.org/10.1371/journal.pntd.0000272,PMC2491585,18698358,CC BY,"BACKGROUND: Genetic variation and rapid evolution are hallmarks of RNA viruses, the result of high mutation rates in RNA replication and selection of mutants that enhance viral adaptation, including the escape from host immune responses. Variability is uneven across the genome because mutations resulting in a deleterious effect on viral fitness are restricted. RNA viruses are thus marked by protein sites permissive to multiple mutations and sites critical to viral structure-function that are evolutionarily robust and highly conserved. Identification and characterization of the historical dynamics of the conserved sites have relevance to multiple applications, including potential targets for diagnosis, and prophylactic and therapeutic purposes. METHODOLOGY/PRINCIPAL FINDINGS: We describe a large-scale identification and analysis of evolutionarily highly conserved amino acid sequences of the entire dengue virus (DENV) proteome, with a focus on sequences of 9 amino acids or more, and thus immune-relevant as potential T-cell determinants. DENV protein sequence data were collected from the NCBI Entrez protein database in 2005 (9,512 sequences) and again in 2007 (12,404 sequences). Forty-four (44) sequences (pan-DENV sequences), mainly those of nonstructural proteins and representing ∼15% of the DENV polyprotein length, were identical in 80% or more of all recorded DENV sequences. Of these 44 sequences, 34 (∼77%) were present in ≥95% of sequences of each DENV type, and 27 (∼61%) were conserved in other Flaviviruses. The frequencies of variants of the pan-DENV sequences were low (0 to ∼5%), as compared to variant frequencies of ∼60 to ∼85% in the non pan-DENV sequence regions. We further showed that the majority of the conserved sequences were immunologically relevant: 34 contained numerous predicted human leukocyte antigen (HLA) supertype-restricted peptide sequences, and 26 contained T-cell determinants identified by studies with HLA-transgenic mice and/or reported to be immunogenic in humans. CONCLUSIONS/SIGNIFICANCE: Forty-four (44) pan-DENV sequences of at least 9 amino acids were highly conserved and identical in 80% or more of all recorded DENV sequences, and the majority were found to be immune-relevant by their correspondence to known or putative HLA-restricted T-cell determinants. The conservation of these sequences through the entire recorded DENV genetic history supports their possible value for diagnosis, prophylactic and/or therapeutic applications. The combination of bioinformatics and experimental approaches applied herein provides a framework for large-scale and systematic analysis of conserved and variable sequences of other pathogens, in particular, for rapidly mutating viruses, such as influenza A virus and HIV.",2008 Aug 13,"['Khan, Asif M.', 'Miotto, Olivo', 'Nascimento, Eduardo J. M.', 'Srinivasan, K. N.', 'Heiny, A. T.', 'Zhang, Guang Lan', 'Marques, E. T.', 'Tan, Tin Wee', 'Brusic, Vladimir', 'Salmon, Jerome', 'August, J. Thomas']",PLoS Negl Trop Dis,,,True
d3738503734864a3cb54929b145611300ebcd4de,PMC,Conservation and Variability of Dengue Virus Proteins: Implications for Vaccine Design,http://dx.doi.org/10.1371/journal.pntd.0000272,PMC2491585,18698358,CC BY,"BACKGROUND: Genetic variation and rapid evolution are hallmarks of RNA viruses, the result of high mutation rates in RNA replication and selection of mutants that enhance viral adaptation, including the escape from host immune responses. Variability is uneven across the genome because mutations resulting in a deleterious effect on viral fitness are restricted. RNA viruses are thus marked by protein sites permissive to multiple mutations and sites critical to viral structure-function that are evolutionarily robust and highly conserved. Identification and characterization of the historical dynamics of the conserved sites have relevance to multiple applications, including potential targets for diagnosis, and prophylactic and therapeutic purposes. METHODOLOGY/PRINCIPAL FINDINGS: We describe a large-scale identification and analysis of evolutionarily highly conserved amino acid sequences of the entire dengue virus (DENV) proteome, with a focus on sequences of 9 amino acids or more, and thus immune-relevant as potential T-cell determinants. DENV protein sequence data were collected from the NCBI Entrez protein database in 2005 (9,512 sequences) and again in 2007 (12,404 sequences). Forty-four (44) sequences (pan-DENV sequences), mainly those of nonstructural proteins and representing ∼15% of the DENV polyprotein length, were identical in 80% or more of all recorded DENV sequences. Of these 44 sequences, 34 (∼77%) were present in ≥95% of sequences of each DENV type, and 27 (∼61%) were conserved in other Flaviviruses. The frequencies of variants of the pan-DENV sequences were low (0 to ∼5%), as compared to variant frequencies of ∼60 to ∼85% in the non pan-DENV sequence regions. We further showed that the majority of the conserved sequences were immunologically relevant: 34 contained numerous predicted human leukocyte antigen (HLA) supertype-restricted peptide sequences, and 26 contained T-cell determinants identified by studies with HLA-transgenic mice and/or reported to be immunogenic in humans. CONCLUSIONS/SIGNIFICANCE: Forty-four (44) pan-DENV sequences of at least 9 amino acids were highly conserved and identical in 80% or more of all recorded DENV sequences, and the majority were found to be immune-relevant by their correspondence to known or putative HLA-restricted T-cell determinants. The conservation of these sequences through the entire recorded DENV genetic history supports their possible value for diagnosis, prophylactic and/or therapeutic applications. The combination of bioinformatics and experimental approaches applied herein provides a framework for large-scale and systematic analysis of conserved and variable sequences of other pathogens, in particular, for rapidly mutating viruses, such as influenza A virus and HIV.",2008 Aug 13,"['Khan, Asif M.', 'Miotto, Olivo', 'Nascimento, Eduardo J. M.', 'Srinivasan, K. N.', 'Heiny, A. T.', 'Zhang, Guang Lan', 'Marques, E. T.', 'Tan, Tin Wee', 'Brusic, Vladimir', 'Salmon, Jerome', 'August, J. Thomas']",PLoS Negl Trop Dis,,,False
26a931d514eb3f80a779ec6d06997e1d77278dd4,PMC,"Topology of evolving, mutagenized viral populations: quasispecies expansion, compression, and operation of negative selection",http://dx.doi.org/10.1186/1471-2148-8-207,PMC2515104,18637173,CC BY,"BACKGROUND: The molecular events and evolutionary forces underlying lethal mutagenesis of virus (or virus extinction through an excess of mutations) are not well understood. Here we apply for the first time phylogenetic methods and Partition Analysis of Quasispecies (PAQ) to monitor genetic distances and intra-population structures of mutant spectra of foot-and-mouth disease virus (FMDV) quasispecies subjected to mutagenesis by base and nucleoside analogues. RESULTS: Phylogenetic and PAQ analyses have revealed a highly dynamic variation of intrapopulation diversity of FMDV quasispecies. The population diversity first suffers striking expansions in the presence of mutagens and then compressions either when the presence of the mutagenic analogue was discontinued or when a mutation that decreased sensitivity to a mutagen was selected. The pattern of mutations found in the populations was in agreement with the behavior of the corresponding nucleotide analogues with FMDV in vitro. Mutations accumulated at preferred genomic sites, and dn/ds ratios indicate the operation of negative (or purifying) selection in populations subjected to mutagenesis. No evidence of unusually elevated genetic distances has been obtained for FMDV populations approaching extinction. CONCLUSION: Phylogenetic and PAQ analysis provide adequate procedures to describe the evolution of viral sequences subjected to lethal mutagenesis. These methods define the changes of intra-population structure more precisely than mutation frequencies and Shannon entropies. PAQ is very sensitive to variations of intrapopulation genetic distances. Strong negative (or purifying) selection operates in FMDV populations subjected to enhanced mutagenesis. The quantifications provide evidence that extinction does not imply unusual increases of intrapopulation complexity, in support of the lethal defection model of virus extinction.",2008 Jul 17,"['Ojosnegros, Samuel', 'Agudo, Rubén', 'Sierra, Macarena', 'Briones, Carlos', 'Sierra, Saleta', 'González- López, Claudia', 'Domingo, Esteban', 'Cristina, Juan']",BMC Evol Biol,,,True
1d45a0c89997d27fe2e01fbee4b407e01cc595c4,PMC,Evolutionary and Transmission Dynamics of Reassortant H5N1 Influenza Virus in Indonesia,http://dx.doi.org/10.1371/journal.ppat.1000130,PMC2515348,18725937,CC BY,"H5N1 highly pathogenic avian influenza (HPAI) viruses have seriously affected the Asian poultry industry since their recurrence in 2003. The viruses pose a threat of emergence of a global pandemic influenza through point mutation or reassortment leading to a strain that can effectively transmit among humans. In this study, we present phylogenetic evidences for the interlineage reassortment among H5N1 HPAI viruses isolated from humans, cats, and birds in Indonesia, and identify the potential genetic parents of the reassorted genome segments. Parsimony analyses of viral phylogeography suggest that the reassortant viruses may have originated from greater Jakarta and surroundings, and subsequently spread to other regions in the West Java province. In addition, Bayesian methods were used to elucidate the genetic diversity dynamics of the reassortant strain and one of its genetic parents, which revealed a more rapid initial growth of genetic diversity in the reassortant viruses relative to their genetic parent. These results demonstrate that interlineage exchange of genetic information may play a pivotal role in determining viral genetic diversity in a focal population. Moreover, our study also revealed significantly stronger diversifying selection on the M1 and PB2 genes in the lineages preceding and subsequent to the emergence of the reassortant viruses, respectively. We discuss how the corresponding mutations might drive the adaptation and onward transmission of the newly formed reassortant viruses.",2008 Aug 22,"['Lam, Tommy Tsan-Yuk', 'Hon, Chung-Chau', 'Pybus, Oliver G.', 'Kosakovsky Pond, Sergei L.', 'Wong, Raymond Tze-Yeung', 'Yip, Chi-Wai', 'Zeng, Fanya', 'Leung, Frederick Chi-Ching']",PLoS Pathog,,,True
402fd2b6ffd34c3d1fb4aca45d84bd7079284d99,PMC,Sampling for Global Epidemic Models and the Topology of an International Airport Network,http://dx.doi.org/10.1371/journal.pone.0003154,PMC2522280,18776932,CC BY,"Mathematical models that describe the global spread of infectious diseases such as influenza, severe acute respiratory syndrome (SARS), and tuberculosis (TB) often consider a sample of international airports as a network supporting disease spread. However, there is no consensus on how many cities should be selected or on how to select those cities. Using airport flight data that commercial airlines reported to the Official Airline Guide (OAG) in 2000, we have examined the network characteristics of network samples obtained under different selection rules. In addition, we have examined different size samples based on largest flight volume and largest metropolitan populations. We have shown that although the bias in network characteristics increases with the reduction of the sample size, a relatively small number of areas that includes the largest airports, the largest cities, the most-connected cities, and the most central cities is enough to describe the dynamics of the global spread of influenza. The analysis suggests that a relatively small number of cities (around 200 or 300 out of almost 3000) can capture enough network information to adequately describe the global spread of a disease such as influenza. Weak traffic flows between small airports can contribute to noise and mask other means of spread such as the ground transportation.",2008 Sep 8,"['Bobashev, Georgiy', 'Morris, Robert J.', 'Goedecke, D. Michael']",PLoS One,,,True
ba4cb142734825c7a8f759f10edfbc58ff798f9c,PMC,Life threatening pneumonia in a lupus patient: a case report,http://dx.doi.org/10.1186/1757-1626-1-70,PMC2526065,18671866,CC BY,"We report a case of systemic lupus erythematosus (SLE) in a 44-year old Caucasian woman complicated with pneumonia and severe respiratory failure requiring ICU treatment and mechanical ventilation. Symptoms developed in a generally well controlled SLE course after sudden stop in immunosupresant therapy (methotrexate, cyclosporin and methylprednisolone). A fulminant course of the disease, an interstitial pattern in a high resolution computed tomography (HRCT) and negative repeated sputum, blood and bronchoaspirate cultures enabled diagnosis of fulminant lupus pneumonitis. The response to pulses of cyclophosphamide and methylprednisolone was good but complicated with a significant leukopenia. HRCT confirmed significant remission of pulmonary changes. Fulminant lupus pneumonitis is a rare but potentially life threatening complication of SLE. Differential diagnosis requires exclusion of pneumonia induced by pathogens such as Pneumocystis jirovevecii (carinii) and Mycobacterium sp. Intensive immunosuppressive therapy and close cooperation between ICU, pulmonology and rheumatology departments is necessary in such a case to minimalize the risk of fatal outcome.",2008 Jul 31,"['Kupczyk, Maciej', 'Antczak, Adam', 'Kuna, Piotr', 'Górski, Paweł']",Cases J,,,True
c851a889568efd469f724ebacfe3270946f3e04f,PMC,Endothelial Cells Support Persistent Gammaherpesvirus 68 Infection,http://dx.doi.org/10.1371/journal.ppat.1000152,PMC2526176,18787698,CC BY,"A variety of human diseases are associated with gammaherpesviruses, including neoplasms of lymphocytes (e.g. Burkitt's lymphoma) and endothelial cells (e.g. Kaposi's sarcoma). Gammaherpesvirus infections usually result in either a productive lytic infection, characterized by expression of all viral genes and rapid cell lysis, or latent infection, characterized by limited viral gene expression and no cell lysis. Here, we report characterization of endothelial cell infection with murine gammaherpesvirus 68 (γHV68), a virus phylogenetically related and biologically similar to the human gammaherpesviruses. Endothelial cells supported γHV68 replication in vitro, but were unique in that a significant proportion of the cells escaped lysis, proliferated, and remained viable in culture for an extended time. Upon infection, endothelial cells became non-adherent and altered in size, complexity, and cell-surface protein expression. These cells were uniformly infected and expressed the lytic transcription program based on detection of abundant viral gene transcripts, GFP fluorescence from the viral genome, and viral surface protein expression. Additionally, endothelial cells continued to produce new infectious virions as late as 30 days post-infection. The outcome of this long-term infection was promoted by the γHV68 v-cyclin, because in the absence of the v-cyclin, viability was significantly reduced following infection. Importantly, infected primary endothelial cells also demonstrated increased viability relative to infected primary fibroblasts, and this increased viability was dependent on the v-cyclin. Finally, we provide evidence for infection of endothelial cells in vivo in immune-deficient mice. The extended viability and virus production of infected endothelial cells indicated that endothelial cells provided a source of prolonged virus production and identify a cell-type specific adaptation of gammaherpesvirus replication. While infected endothelial cells would likely be cleared in a healthy individual, persistently infected endothelial cells could provide a source of continued virus replication in immune-compromised individuals, a context in which gammaherpesvirus-associated pathology frequently occurs.",2008 Sep 12,"['Suárez, Andrea Luísa', 'van Dyk, Linda Faye']",PLoS Pathog,,,True
35808155b612d2189d338168dc1cc0e0b7401661,PMC,Selection of reference genes for qRT-PCR examination of wild populations of Atlantic cod Gadus morhua,http://dx.doi.org/10.1186/1756-0500-1-47,PMC2527504,18710500,CC BY,"BACKGROUND: Extensive sequencing efforts have been taking place for the Atlantic cod (Gadus morhua) in recent years, the number of ESTs in the Genbank has reached more than 140.000. Despite its importance in North Atlantic fisheries and potential use in aquaculture, relatively few gene expression examination exists for this species, and systematic evaluations of reference gene stability in quantitative real-time RT-PCR (qRT-PCR) studies are lacking. RESULTS: The stability of 10 potential reference genes was examined in six tissues of Atlantic cod obtained from four populations, to determine the most suitable genes to be used in qRT-PCR analyses. Relative transcription levels of genes encoding β-actin (ACTB), elongation factor 1A (EF1A), actin-related protein-2 (ARP-2), glyceraldehyde-3P-dehydrogenase (GAPDH), ubiquitin (Ubi), acidic ribosomal protein (ARP), ribosomal protein S9 (S9), ribosomal protein L4 (RPL4), RPL22 and RPL37 were quantified in gills, brain, liver, head kidney, muscle and middle intestine in six juvenile fish from three wild populations and from farmed Atlantic cod. Reference gene stability was investigated using the geNorm and NormFinder tools. Based on calculations performed with the geNorm, which determines the most stable genes from a set of tested genes in a given cDNA sample, ARP, Ubi, S9 and RPL37 were among the most stable genes in all tissues. When the same calculations were done with NormFinder, the same genes plus RPL4 and EF1A were ranked as the preferable genes. CONCLUSION: Overall, this work suggests that the Ubi and ARP can be useful as reference genes in qRT-PCR examination of gene expression studying wild populations of Atlantic cod.",2008 Jul 16,"['Olsvik, Pål A', 'Søfteland, Liv', 'Lie, Kai K']",BMC Res Notes,,,True
524020333ab93c945ffd02838cb08672703724c1,PMC,Lentivirus Display: Stable Expression of Human Antibodies on the Surface of Human Cells and Virus Particles,http://dx.doi.org/10.1371/journal.pone.0003181,PMC2527531,18784843,CC BY,"BACKGROUND: Isolation of human antibodies using current display technologies can be limited by constraints on protein expression, folding and post-translational modifications. Here we describe a discovery platform that utilizes self-inactivating (SIN) lentiviral vectors for the surface display of high-affinity single-chain variable region (scFv) antibody fragments on human cells and lentivirus particles. METHODOLOGY/PRINCIPAL FINDINGS: Bivalent scFvFc human antibodies were fused in frame with different transmembrane (TM) anchoring moieties to allow efficient high-level expression on human cells and the optimal TM was identified. The addition of an eight amino acid HIV-1 gp41 envelope incorporation motif further increased scFvFc expression on human cells and incorporation into lentiviral particles. Both antibody-displaying human cells and virus particles bound antigen specifically. Sulfation of CDR tyrosine residues, a property recently shown to broaden antibody binding affinity and antigen recognition was also demonstrated. High level scFvFc expression and stable integration was achieved in human cells following transduction with IRES containing bicistronic SIN lentivectors encoding ZsGreen when scFvFc fusion proteins were expressed from the first cassette. Up to 10(6)-fold enrichment of antibody expressing cells was achieved with one round of antigen coupled magnetic bead pre-selection followed by FACS sorting. Finally, the scFvFc displaying human cells could be used directly in functional biological screens with remarkable sensitivity. CONCLUSIONS/SIGNIFICANCE: This antibody display platform will complement existing technologies by virtue of providing properties unique to lentiviruses and antibody expression in human cells, which, in turn, may aid the discovery of novel therapeutic human mAbs.",2008 Sep 11,"['Taube, Ran', 'Zhu, Quan', 'Xu, Chen', 'Diaz-Griffero, Felipe', 'Sui, Jianhua', 'Kamau, Erick', 'Dwyer, Markryan', 'Aird, Daniel', 'Marasco, Wayne A.']",PLoS One,,,True
2afcf2ab2330cb56ec493f82d87fa0c5b5f076e9,PMC,Improving antibiotic prescribing for adults with community acquired pneumonia: Does a computerised decision support system achieve more than academic detailing alone? – a time series analysis,http://dx.doi.org/10.1186/1472-6947-8-35,PMC2527556,18667084,CC BY,"BACKGROUND: The ideal method to encourage uptake of clinical guidelines in hospitals is not known. Several strategies have been suggested. This study evaluates the impact of academic detailing and a computerised decision support system (CDSS) on clinicians' prescribing behaviour for patients with community acquired pneumonia (CAP). METHODS: The management of all patients presenting to the emergency department over three successive time periods was evaluated; the baseline, academic detailing and CDSS periods. The rate of empiric antibiotic prescribing that was concordant with recommendations was studied over time comparing pre and post periods and using an interrupted time series analysis. RESULTS: The odds ratio for concordant therapy in the academic detailing period, after adjustment for age, illness severity and suspicion of aspiration, compared with the baseline period was OR = 2.79 [1.88, 4.14], p < 0.01, and for the computerised decision support period compared to the academic detailing period was OR = 1.99 [1.07, 3.69], p = 0.02. During the first months of the computerised decision support period an improvement in the appropriateness of antibiotic prescribing was demonstrated, which was greater than that expected to have occurred with time and academic detailing alone, based on predictions from a binary logistic model. CONCLUSION: Deployment of a computerised decision support system was associated with an early improvement in antibiotic prescribing practices which was greater than the changes seen with academic detailing. The sustainability of this intervention requires further evaluation.",2008 Jul 31,"['Buising, Kirsty L', 'Thursky, Karin A', 'Black, James F', 'MacGregor, Lachlan', 'Street, Alan C', 'Kennedy, Marcus P', 'Brown, Graham V']",BMC Med Inform Decis Mak,,,True
b890aa8cb8a15fec0f4bb8e970f5a21fd2dfda33,PMC,Loop-mediated isothermal amplification as an emerging technology for detection of Yersinia ruckeri the causative agent of enteric red mouth disease in fish,http://dx.doi.org/10.1186/1746-6148-4-31,PMC2531098,18700011,CC BY,"BACKGROUND: Enteric Redmouth (ERM) disease also known as Yersiniosis is a contagious disease affecting salmonids, mainly rainbow trout. The causative agent is the gram-negative bacterium Yersinia ruckeri. The disease can be diagnosed by isolation and identification of the causative agent, or detection of the Pathogen using fluorescent antibody tests, ELISA and PCR assays. These diagnostic methods are laborious, time consuming and need well trained personnel. RESULTS: A loop-mediated isothermal amplification (LAMP) assay was developed and evaluated for detection of Y. ruckeri the etiological agent of enteric red mouth (ERM) disease in salmonids. The assay was optimised to amplify the yruI/yruR gene, which encodes Y. ruckeri quorum sensing system, in the presence of a specific primer set and Bst DNA polymerase at an isothermal temperature of 63°C for one hour. Amplification products were detected by visual inspection, agarose gel electrophoresis and by real-time monitoring of turbidity resulted by formation of LAMP amplicons. Digestion with HphI restriction enzyme demonstrated that the amplified product was unique. The specificity of the assay was verified by the absence of amplification products when tested against related bacteria. The assay had 10-fold higher sensitivity compared with conventional PCR and successfully detected Y. ruckeri not only in pure bacterial culture but also in tissue homogenates of infected fish. CONCLUSION: The ERM-LAMP assay represents a practical alternative to the microbiological approach for rapid, sensitive and specific detection of Y. ruckeri in fish farms. The assay is carried out in one hour and needs only a heating block or water bath as laboratory furniture. The advantages of the ERM-LAMP assay make it a promising tool for molecular detection of enteric red mouth disease in fish farms.",2008 Aug 12,"['Saleh, Mona', 'Soliman, Hatem', 'El-Matbouli, Mansour']",BMC Vet Res,,,True
3df8818685d06d65f93674101b8ca899731efc36,PMC,Rabies trend in China (1990–2007) and post-exposure prophylaxis in the Guangdong province,http://dx.doi.org/10.1186/1471-2334-8-113,PMC2532688,18717989,CC BY,"BACKGROUND: Rabies is a major public-health problem in developing countries such as China. Although the recent re-emergence of human rabies in China was noted in several epidemiological studies, little attention was paid to the reasons behind this phenomenon paralleling the findings of the previous reports. The purpose of this study is thus first to characterize the current trends of human rabies in China from 1990 to 2007, and then to define better recommendations for improving the post-exposure prophylaxis (PEP) schedules delivered to rabies patients. METHODS: The most updated epidemiological data for 22527 human rabies cases from January 1990 to July 2007, retrieved from the surveillance database of reportable diseases managed by the Ministry of Health of China, were analysed. To investigate the efficiency for the post-exposure treatment of rabies, the details of 244 rabies patients, including their anti-rabies treatment of injuries or related incidents, were ascertained in Guangdong provincial jurisdiction. The risk factors to which the patients were predisposed or the regimens given to 80 patients who received any type of PEP were analysed to identify the reasons for the PEP failures. RESULTS: The results from analysis of the large number of human rabies cases showed that rabies in China was largely under control during the period 1990–1996. However, there has been a large jump in the number of reported rabies cases since 2001 up to a new peak (with an incidence rate of 0.20 per 100000 people) that was reached in 2004, and where the level has remained until present. Then, we analysed the PEP in 244 rabies cases collected in the Guangdong province in 2003 and 2004, and found that 67.2% of the patients did not seek medical services or did not receive any PEP. Further analysis of PEP for the 80 rabies patients who received any type of PEP indicated that almost all of the patients did not receive proper or timely treatment on the wounds or post-exposure vaccination or rabies immunoglobulins. CONCLUSION: While the issue of under-reporting of rabies in previous years may well be a factor in the apparent upwards trend of human rabies in recent years, the analysis of PEP in the Guangdong province provides evidence that suggests that the failure to receive PEP was a major factor in the number of human cases in China. Thus, the data underline the need for greatly improved availability and timely application of high-quality anti-rabies biologicals, both vaccines and immunoglobulins, in the treatment of human bite victims. Controlling dog rabies through pet vaccination schemes may also play a huge role in reducing the rate of human exposure. Education of the public, health care staff and veterinarians will also help to change the current situation.",2008 Aug 21,"['Si, Han', 'Guo, Zhong-Min', 'Hao, Yuan-Tao', 'Liu, Yu-Ge', 'Zhang, Ding-Mei', 'Rao, Shao-Qi', 'Lu, Jia-Hai']",BMC Infect Dis,,,True
4d0b62b91c66f47c6aff69dfa0ed2c25ffe064ae,PMC,Rapid Identification of Known and New RNA Viruses from Animal Tissues,http://dx.doi.org/10.1371/journal.ppat.1000163,PMC2533695,18818738,CC BY,"Viral surveillance programs or diagnostic labs occasionally obtain infectious samples that fail to be typed by available cell culture, serological, or nucleic acid tests. Five such samples, originating from insect pools, skunk brain, human feces and sewer effluent, collected between 1955 and 1980, resulted in pathology when inoculated into suckling mice. In this study, sequence-independent amplification of partially purified viral nucleic acids and small scale shotgun sequencing was used on mouse brain and muscle tissues. A single viral agent was identified in each sample. For each virus, between 16% to 57% of the viral genome was acquired by sequencing only 42–108 plasmid inserts. Viruses derived from human feces or sewer effluent belonged to the Picornaviridae family and showed between 80% to 91% amino acid identities to known picornaviruses. The complete polyprotein sequence of one virus showed strong similarity to a simian picornavirus sequence in the provisional Sapelovirus genus. Insects and skunk derived viral sequences exhibited amino acid identities ranging from 25% to 98% to the segmented genomes of viruses within the Reoviridae family. Two isolates were highly divergent: one is potentially a new species within the orthoreovirus genus, and the other is a new species within the orbivirus genus. We demonstrate that a simple, inexpensive, and rapid metagenomics approach is effective for identifying known and highly divergent new viruses in homogenized tissues of acutely infected mice.",2008 Sep 26,"['Victoria, Joseph G.', 'Kapoor, Amit', 'Dupuis, Kent', 'Schnurr, David P.', 'Delwart, Eric L.']",PLoS Pathog,,,True
82ef5d93dc7dd6b35e8411969e33633b402e5acc,PMC,SARS-Coronavirus Replication Is Supported by a Reticulovesicular Network of Modified Endoplasmic Reticulum,http://dx.doi.org/10.1371/journal.pbio.0060226,PMC2535663,18798692,CC BY,"Positive-strand RNA viruses, a large group including human pathogens such as SARS-coronavirus (SARS-CoV), replicate in the cytoplasm of infected host cells. Their replication complexes are commonly associated with modified host cell membranes. Membrane structures supporting viral RNA synthesis range from distinct spherular membrane invaginations to more elaborate webs of packed membranes and vesicles. Generally, their ultrastructure, morphogenesis, and exact role in viral replication remain to be defined. Poorly characterized double-membrane vesicles (DMVs) were previously implicated in SARS-CoV RNA synthesis. We have now applied electron tomography of cryofixed infected cells for the three-dimensional imaging of coronavirus-induced membrane alterations at high resolution. Our analysis defines a unique reticulovesicular network of modified endoplasmic reticulum that integrates convoluted membranes, numerous interconnected DMVs (diameter 200–300 nm), and “vesicle packets” apparently arising from DMV merger. The convoluted membranes were most abundantly immunolabeled for viral replicase subunits. However, double-stranded RNA, presumably revealing the site of viral RNA synthesis, mainly localized to the DMV interior. Since we could not discern a connection between DMV interior and cytosol, our analysis raises several questions about the mechanism of DMV formation and the actual site of SARS-CoV RNA synthesis. Our data document the extensive virus-induced reorganization of host cell membranes into a network that is used to organize viral replication and possibly hide replicating RNA from antiviral defense mechanisms. Together with biochemical studies of the viral enzyme complex, our ultrastructural description of this “replication network” will aid to further dissect the early stages of the coronavirus life cycle and its virus-host interactions.",2008 Sep 16,"['Knoops, Kèvin', 'Kikkert, Marjolein', 'van den Worm, Sjoerd H. E.', 'Zevenhoven-Dobbe, Jessika C', 'van der Meer, Yvonne', 'Koster, Abraham J', 'Mommaas, A. Mieke', 'Snijder, Eric J']",PLoS Biol,,,True
155cca2a90a5430ac391b46983efa4c13f193289,PMC,Phi29 polymerase based random amplification of viral RNA as an alternative to random RT-PCR,http://dx.doi.org/10.1186/1471-2199-9-77,PMC2535778,18771595,CC BY,"BACKGROUND: Phi29 polymerase based amplification methods provides amplified DNA with minimal changes in sequence and relative abundance for many biomedical applications. RNA virus detection using microarrays, however, can present a challenge because phi29 DNA polymerase cannot amplify RNA nor small cDNA fragments (<2000 bases) obtained by reverse transcription of certain viral RNA genomes. Therefore, ligation of cDNA fragments is necessary prior phi29 polymerase based amplification. We adapted the QuantiTect Whole Transcriptome Kit (Qiagen) to our purposes and designated the method as Whole Transcriptome Amplification (WTA). RESULTS: WTA successfully amplified cDNA from a panel of RNA viruses representing the diversity of ribovirus genome sizes. We amplified a range of genome copy numbers from 15 to 4 × 10(7 )using WTA, which yielded quantities of amplified DNA as high as 1.2 μg/μl or 10(10 )target copies. The amplification factor varied between 10(9 )and 10(6). We also demonstrated that co-amplification occurred when viral RNA was mixed with bacterial DNA. CONCLUSION: This is the first report in the scientific literature showing that a modified WGA (WTA) approach can be successfully applied to viral genomic RNA of all sizes. Amplifying viral RNA by WTA provides considerably better sensitivity and accuracy of detection compared to random RT-PCR.",2008 Sep 4,"['Berthet, Nicolas', 'Reinhardt, Anita K', 'Leclercq, India', 'van Ooyen, Sven', 'Batéjat, Christophe', 'Dickinson, Philip', 'Stamboliyska, Rayna', 'Old, Iain G', 'Kong, Katherine A', 'Dacheux, Laurent', 'Bourhy, Hervé', 'Kennedy, Giulia C', 'Korfhage, Christian', 'Cole, Stewart T', 'Manuguerra, Jean-Claude']",BMC Mol Biol,,,True
06cf324e3d0f793e5c722894c6ea6949655b1f10,PMC,Development of human antibody fragments using antibody phage display for the detection and diagnosis of Venezuelan equine encephalitis virus (VEEV),http://dx.doi.org/10.1186/1472-6750-8-66,PMC2543005,18764933,CC BY,"BACKGROUND: Venezuelan equine encephalitis virus (VEEV) belongs to the Alphavirus group. Several species of this family are also pathogenic to humans and are recognized as potential agents of biological warfare and terrorism. The objective of this work was the generation of recombinant antibodies for the detection of VEEV after a potential bioterrorism assault or an natural outbreak of VEEV. RESULTS: In this work, human anti-VEEV single chain Fragments variable (scFv) were isolated for the first time from a human naïve antibody gene library using optimized selection processes. In total eleven different scFvs were identified and their immunological specificity was assessed. The specific detection of the VEEV strains TC83, H12/93 and 230 by the selected antibody fragments was proved. Active as well as formalin inactivated virus particles were recognized by the selected antibody fragments which could be also used for Western blot analysis of VEEV proteins and immunohistochemistry of VEEV infected cells. The anti-VEEV scFv phage clones did not show any cross-reactivity with Alphavirus species of the Western equine encephalitis virus (WEEV) and Eastern equine encephalitis virus (EEEV) antigenic complex, nor did they react with Chikungunya virus (CHIKV), if they were used as detection reagent. CONCLUSION: For the first time, this study describes the selection of antibodies against a human pathogenic virus from a human naïve scFv antibody gene library using complete, active virus particles as antigen. The broad and sensitive applicability of scFv-presenting phage for the immunological detection and diagnosis of Alphavirus species was demonstrated. The selected antibody fragments will improve the fast identification of VEEV in case of a biological warfare or terroristic attack or a natural outbreak.",2008 Sep 2,"['Kirsch, Martina Inga', 'Hülseweh, Birgit', 'Nacke, Christoph', 'Rülker, Torsten', 'Schirrmann, Thomas', 'Marschall, Hans-Jürgen', 'Hust, Michael', 'Dübel, Stefan']",BMC Biotechnol,,,True
52264dd990e495e82f511cfa80a14b52ec063722,PMC,Control of asthma triggers in indoor air with air cleaners: a modeling analysis,http://dx.doi.org/10.1186/1476-069X-7-43,PMC2543006,18684328,CC BY,"BACKGROUND: Reducing exposure to environmental agents indoors shown to increase asthma symptoms or lead to asthma exacerbations is an important component of a strategy to manage asthma for individuals. Numerous investigations have demonstrated that portable air cleaning devices can reduce concentrations of asthma triggers in indoor air; however, their benefits for breathing problems have not always been reproducible. The potential exposure benefits of whole house high efficiency in-duct air cleaners for sensitive subpopulations have yet to be evaluated. METHODS: We used an indoor air quality modeling system (CONTAM) developed by NIST to examine peak and time-integrated concentrations of common asthma triggers present in indoor air over a year as a function of natural ventilation, portable air cleaners, and forced air ventilation equipped with conventional and high efficiency filtration systems. Emission rates for asthma triggers were based on experimental studies published in the scientific literature. RESULTS: Forced air systems with high efficiency filtration were found to provide the best control of asthma triggers: 30–55% lower cat allergen levels, 90–99% lower risk of respiratory infection through the inhalation route of exposure, 90–98% lower environmental tobacco smoke (ETS) levels, and 50–75% lower fungal spore levels than the other ventilation/filtration systems considered. These results indicate that the use of high efficiency in-duct air cleaners provide an effective means of controlling allergen levels not only in a single room, like a portable air cleaner, but the whole house. CONCLUSION: These findings are useful for evaluating potential benefits of high efficiency in-duct filtration systems for controlling exposure to asthma triggers indoors and for the design of trials of environmental interventions intended to evaluate their utility in practice.",2008 Aug 6,"['Myatt, Theodore A', 'Minegishi, Taeko', 'Allen, Joseph G', 'MacIntosh, David L']",Environ Health,,,True
61974b05fc434de7782d10056e719e7d1bdda66d,PMC,Control of asthma triggers in indoor air with air cleaners: a modeling analysis,http://dx.doi.org/10.1186/1476-069X-7-43,PMC2543006,18684328,CC BY,"BACKGROUND: Reducing exposure to environmental agents indoors shown to increase asthma symptoms or lead to asthma exacerbations is an important component of a strategy to manage asthma for individuals. Numerous investigations have demonstrated that portable air cleaning devices can reduce concentrations of asthma triggers in indoor air; however, their benefits for breathing problems have not always been reproducible. The potential exposure benefits of whole house high efficiency in-duct air cleaners for sensitive subpopulations have yet to be evaluated. METHODS: We used an indoor air quality modeling system (CONTAM) developed by NIST to examine peak and time-integrated concentrations of common asthma triggers present in indoor air over a year as a function of natural ventilation, portable air cleaners, and forced air ventilation equipped with conventional and high efficiency filtration systems. Emission rates for asthma triggers were based on experimental studies published in the scientific literature. RESULTS: Forced air systems with high efficiency filtration were found to provide the best control of asthma triggers: 30–55% lower cat allergen levels, 90–99% lower risk of respiratory infection through the inhalation route of exposure, 90–98% lower environmental tobacco smoke (ETS) levels, and 50–75% lower fungal spore levels than the other ventilation/filtration systems considered. These results indicate that the use of high efficiency in-duct air cleaners provide an effective means of controlling allergen levels not only in a single room, like a portable air cleaner, but the whole house. CONCLUSION: These findings are useful for evaluating potential benefits of high efficiency in-duct filtration systems for controlling exposure to asthma triggers indoors and for the design of trials of environmental interventions intended to evaluate their utility in practice.",2008 Aug 6,"['Myatt, Theodore A', 'Minegishi, Taeko', 'Allen, Joseph G', 'MacIntosh, David L']",Environ Health,,,False
f818f2753bb690f66cdd53852c07db6e0c1d46f3,PMC,Control of asthma triggers in indoor air with air cleaners: a modeling analysis,http://dx.doi.org/10.1186/1476-069X-7-43,PMC2543006,18684328,CC BY,"BACKGROUND: Reducing exposure to environmental agents indoors shown to increase asthma symptoms or lead to asthma exacerbations is an important component of a strategy to manage asthma for individuals. Numerous investigations have demonstrated that portable air cleaning devices can reduce concentrations of asthma triggers in indoor air; however, their benefits for breathing problems have not always been reproducible. The potential exposure benefits of whole house high efficiency in-duct air cleaners for sensitive subpopulations have yet to be evaluated. METHODS: We used an indoor air quality modeling system (CONTAM) developed by NIST to examine peak and time-integrated concentrations of common asthma triggers present in indoor air over a year as a function of natural ventilation, portable air cleaners, and forced air ventilation equipped with conventional and high efficiency filtration systems. Emission rates for asthma triggers were based on experimental studies published in the scientific literature. RESULTS: Forced air systems with high efficiency filtration were found to provide the best control of asthma triggers: 30–55% lower cat allergen levels, 90–99% lower risk of respiratory infection through the inhalation route of exposure, 90–98% lower environmental tobacco smoke (ETS) levels, and 50–75% lower fungal spore levels than the other ventilation/filtration systems considered. These results indicate that the use of high efficiency in-duct air cleaners provide an effective means of controlling allergen levels not only in a single room, like a portable air cleaner, but the whole house. CONCLUSION: These findings are useful for evaluating potential benefits of high efficiency in-duct filtration systems for controlling exposure to asthma triggers indoors and for the design of trials of environmental interventions intended to evaluate their utility in practice.",2008 Aug 6,"['Myatt, Theodore A', 'Minegishi, Taeko', 'Allen, Joseph G', 'MacIntosh, David L']",Environ Health,,,False
43f0ed0ead4058d6f92c7390c15d0d9fe66af448,PMC,Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: Identification of a candidate etiologic agent,http://dx.doi.org/10.1186/1743-422X-5-88,PMC2546392,18671869,CC BY,"BACKGROUND: Proventricular dilatation disease (PDD) is a fatal disorder threatening domesticated and wild psittacine birds worldwide. It is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system, leading to central nervous system disorders as well as disordered enteric motility and associated wasting. For almost 40 years, a viral etiology for PDD has been suspected, but to date no candidate etiologic agent has been reproducibly linked to the disease. RESULTS: Analysis of 2 PDD case-control series collected independently on different continents using a pan-viral microarray revealed a bornavirus hybridization signature in 62.5% of the PDD cases (5/8) and none of the controls (0/8). Ultra high throughput sequencing was utilized to recover the complete viral genome sequence from one of the virus-positive PDD cases. This revealed a bornavirus-like genome organization for this agent with a high degree of sequence divergence from all prior bornavirus isolates. We propose the name avian bornavirus (ABV) for this agent. Further specific ABV PCR analysis of an additional set of independently collected PDD cases and controls yielded a significant difference in ABV detection rate among PDD cases (71%, n = 7) compared to controls (0%, n = 14) (P = 0.01; Fisher's Exact Test). Partial sequence analysis of a total of 16 ABV isolates we have now recovered from these and an additional set of cases reveals at least 5 distinct ABV genetic subgroups. CONCLUSION: These studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD.",2008 Jul 31,"['Kistler, Amy L', 'Gancz, Ady', 'Clubb, Susan', 'Skewes-Cox, Peter', 'Fischer, Kael', 'Sorber, Katherine', 'Chiu, Charles Y', 'Lublin, Avishai', 'Mechani, Sara', 'Farnoushi, Yigal', 'Greninger, Alexander', 'Wen, Christopher C', 'Karlene, Scott B', 'Ganem, Don', 'DeRisi, Joseph L']",Virol J,,,True
15cded6cc0f782faabb4abb5dfd91c48a831e2a3,PMC,Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: Identification of a candidate etiologic agent,http://dx.doi.org/10.1186/1743-422X-5-88,PMC2546392,18671869,CC BY,"BACKGROUND: Proventricular dilatation disease (PDD) is a fatal disorder threatening domesticated and wild psittacine birds worldwide. It is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system, leading to central nervous system disorders as well as disordered enteric motility and associated wasting. For almost 40 years, a viral etiology for PDD has been suspected, but to date no candidate etiologic agent has been reproducibly linked to the disease. RESULTS: Analysis of 2 PDD case-control series collected independently on different continents using a pan-viral microarray revealed a bornavirus hybridization signature in 62.5% of the PDD cases (5/8) and none of the controls (0/8). Ultra high throughput sequencing was utilized to recover the complete viral genome sequence from one of the virus-positive PDD cases. This revealed a bornavirus-like genome organization for this agent with a high degree of sequence divergence from all prior bornavirus isolates. We propose the name avian bornavirus (ABV) for this agent. Further specific ABV PCR analysis of an additional set of independently collected PDD cases and controls yielded a significant difference in ABV detection rate among PDD cases (71%, n = 7) compared to controls (0%, n = 14) (P = 0.01; Fisher's Exact Test). Partial sequence analysis of a total of 16 ABV isolates we have now recovered from these and an additional set of cases reveals at least 5 distinct ABV genetic subgroups. CONCLUSION: These studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD.",2008 Jul 31,"['Kistler, Amy L', 'Gancz, Ady', 'Clubb, Susan', 'Skewes-Cox, Peter', 'Fischer, Kael', 'Sorber, Katherine', 'Chiu, Charles Y', 'Lublin, Avishai', 'Mechani, Sara', 'Farnoushi, Yigal', 'Greninger, Alexander', 'Wen, Christopher C', 'Karlene, Scott B', 'Ganem, Don', 'DeRisi, Joseph L']",Virol J,,,False
a2c3e84cdf13b1c02cdeb286515e4745d33bfc10,PMC,Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: Identification of a candidate etiologic agent,http://dx.doi.org/10.1186/1743-422X-5-88,PMC2546392,18671869,CC BY,"BACKGROUND: Proventricular dilatation disease (PDD) is a fatal disorder threatening domesticated and wild psittacine birds worldwide. It is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system, leading to central nervous system disorders as well as disordered enteric motility and associated wasting. For almost 40 years, a viral etiology for PDD has been suspected, but to date no candidate etiologic agent has been reproducibly linked to the disease. RESULTS: Analysis of 2 PDD case-control series collected independently on different continents using a pan-viral microarray revealed a bornavirus hybridization signature in 62.5% of the PDD cases (5/8) and none of the controls (0/8). Ultra high throughput sequencing was utilized to recover the complete viral genome sequence from one of the virus-positive PDD cases. This revealed a bornavirus-like genome organization for this agent with a high degree of sequence divergence from all prior bornavirus isolates. We propose the name avian bornavirus (ABV) for this agent. Further specific ABV PCR analysis of an additional set of independently collected PDD cases and controls yielded a significant difference in ABV detection rate among PDD cases (71%, n = 7) compared to controls (0%, n = 14) (P = 0.01; Fisher's Exact Test). Partial sequence analysis of a total of 16 ABV isolates we have now recovered from these and an additional set of cases reveals at least 5 distinct ABV genetic subgroups. CONCLUSION: These studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD.",2008 Jul 31,"['Kistler, Amy L', 'Gancz, Ady', 'Clubb, Susan', 'Skewes-Cox, Peter', 'Fischer, Kael', 'Sorber, Katherine', 'Chiu, Charles Y', 'Lublin, Avishai', 'Mechani, Sara', 'Farnoushi, Yigal', 'Greninger, Alexander', 'Wen, Christopher C', 'Karlene, Scott B', 'Ganem, Don', 'DeRisi, Joseph L']",Virol J,,,False
28619df1e1f9d348dd517aeb7d20e7c4bfa5790a,PMC,Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: Identification of a candidate etiologic agent,http://dx.doi.org/10.1186/1743-422X-5-88,PMC2546392,18671869,CC BY,"BACKGROUND: Proventricular dilatation disease (PDD) is a fatal disorder threatening domesticated and wild psittacine birds worldwide. It is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system, leading to central nervous system disorders as well as disordered enteric motility and associated wasting. For almost 40 years, a viral etiology for PDD has been suspected, but to date no candidate etiologic agent has been reproducibly linked to the disease. RESULTS: Analysis of 2 PDD case-control series collected independently on different continents using a pan-viral microarray revealed a bornavirus hybridization signature in 62.5% of the PDD cases (5/8) and none of the controls (0/8). Ultra high throughput sequencing was utilized to recover the complete viral genome sequence from one of the virus-positive PDD cases. This revealed a bornavirus-like genome organization for this agent with a high degree of sequence divergence from all prior bornavirus isolates. We propose the name avian bornavirus (ABV) for this agent. Further specific ABV PCR analysis of an additional set of independently collected PDD cases and controls yielded a significant difference in ABV detection rate among PDD cases (71%, n = 7) compared to controls (0%, n = 14) (P = 0.01; Fisher's Exact Test). Partial sequence analysis of a total of 16 ABV isolates we have now recovered from these and an additional set of cases reveals at least 5 distinct ABV genetic subgroups. CONCLUSION: These studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD.",2008 Jul 31,"['Kistler, Amy L', 'Gancz, Ady', 'Clubb, Susan', 'Skewes-Cox, Peter', 'Fischer, Kael', 'Sorber, Katherine', 'Chiu, Charles Y', 'Lublin, Avishai', 'Mechani, Sara', 'Farnoushi, Yigal', 'Greninger, Alexander', 'Wen, Christopher C', 'Karlene, Scott B', 'Ganem, Don', 'DeRisi, Joseph L']",Virol J,,,False
a2e4c6efa8b851cd3519485c77941d2ec4c4b15c,PMC,Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: Identification of a candidate etiologic agent,http://dx.doi.org/10.1186/1743-422X-5-88,PMC2546392,18671869,CC BY,"BACKGROUND: Proventricular dilatation disease (PDD) is a fatal disorder threatening domesticated and wild psittacine birds worldwide. It is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system, leading to central nervous system disorders as well as disordered enteric motility and associated wasting. For almost 40 years, a viral etiology for PDD has been suspected, but to date no candidate etiologic agent has been reproducibly linked to the disease. RESULTS: Analysis of 2 PDD case-control series collected independently on different continents using a pan-viral microarray revealed a bornavirus hybridization signature in 62.5% of the PDD cases (5/8) and none of the controls (0/8). Ultra high throughput sequencing was utilized to recover the complete viral genome sequence from one of the virus-positive PDD cases. This revealed a bornavirus-like genome organization for this agent with a high degree of sequence divergence from all prior bornavirus isolates. We propose the name avian bornavirus (ABV) for this agent. Further specific ABV PCR analysis of an additional set of independently collected PDD cases and controls yielded a significant difference in ABV detection rate among PDD cases (71%, n = 7) compared to controls (0%, n = 14) (P = 0.01; Fisher's Exact Test). Partial sequence analysis of a total of 16 ABV isolates we have now recovered from these and an additional set of cases reveals at least 5 distinct ABV genetic subgroups. CONCLUSION: These studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD.",2008 Jul 31,"['Kistler, Amy L', 'Gancz, Ady', 'Clubb, Susan', 'Skewes-Cox, Peter', 'Fischer, Kael', 'Sorber, Katherine', 'Chiu, Charles Y', 'Lublin, Avishai', 'Mechani, Sara', 'Farnoushi, Yigal', 'Greninger, Alexander', 'Wen, Christopher C', 'Karlene, Scott B', 'Ganem, Don', 'DeRisi, Joseph L']",Virol J,,,False
0a00a6df208e068e7aa369fb94641434ea0e6070,PMC,Novel genome polymorphisms in BCG vaccine strains and impact on efficacy,http://dx.doi.org/10.1186/1471-2164-9-413,PMC2553098,18793412,CC BY,"Bacille Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis currently used as a vaccine against tuberculosis. Global distribution and propagation of BCG has contributed to the in vitro evolution of the vaccine strain and is thought to partially account for the different outcomes of BCG vaccine trials. Previous efforts by several molecular techniques effectively identified large sequence polymorphisms among BCG daughter strains, but lacked the resolution to identify smaller changes. In this study, we have used a NimbleGen tiling array for whole genome comparison of 13 BCG strains. Using this approach, in tandem with DNA resequencing, we have identified six novel large sequence polymorphisms including four deletions and two duplications in specific BCG strains. Moreover, we have uncovered various polymorphisms in the phoP-phoR locus. Importantly, these polymorphisms affect genes encoding established virulence factors including cell wall complex lipids, ESX secretion systems, and the PhoP-PhoR two-component system. Our study demonstrates that major virulence factors are different among BCG strains, which provide molecular mechanisms for important vaccine phenotypes including adverse effect profile, tuberculin reactivity and protective efficacy. These findings have important implications for the development of a new generation of vaccines.",2008 Sep 15,"['Leung, Andrea S', 'Tran, Vanessa', 'Wu, Zuowei', 'Yu, Xuping', 'Alexander, David C', 'Gao, George Fu', 'Zhu, Baoli', 'Liu, Jun']",BMC Genomics,,,True
bbbeb27419905cbacf36b6932302650784570099,PMC,Genome-Wide Analysis of Protein-Protein Interactions and Involvement of Viral Proteins in SARS-CoV Replication,http://dx.doi.org/10.1371/journal.pone.0003299,PMC2553179,18827877,CC BY,"Analyses of viral protein-protein interactions are an important step to understand viral protein functions and their underlying molecular mechanisms. In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV) and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Three pairs of the interactions identified were detected in both directions: non-structural protein (nsp) 10 and nsp14, nsp10 and nsp16, and nsp7 and nsp8. The interactions between the multifunctional nsp10 and nsp14 or nsp16, which are the unique proteins found in the members of Nidovirales with large RNA genomes including coronaviruses and toroviruses, may have important implication for the mechanisms of replication/transcription complex assembly and functions of these viruses. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12) provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. Collectively, our findings provide a basis and platform for further characterization of the functions and mechanisms of coronavirus proteins.",2008 Oct 1,"[""Pan, Ji'An"", 'Peng, Xiaoxue', 'Gao, Yajing', 'Li, Zhilin', 'Lu, Xiaolu', 'Chen, Yingzhao', 'Ishaq, Musarat', 'Liu, Dan', 'DeDiego, Marta L.', 'Enjuanes, Luis', 'Guo, Deyin']",PLoS One,,,True
010ad052b58172981e089bc73b9ad16a732960f2,PMC,Activation of the Unfolded Protein Response Is Required for Defenses against Bacterial Pore-Forming Toxin In Vivo,http://dx.doi.org/10.1371/journal.ppat.1000176,PMC2553261,18846208,CC BY,"Pore-forming toxins (PFTs) constitute the single largest class of proteinaceous bacterial virulence factors and are made by many of the most important bacterial pathogens. Host responses to these toxins are complex and poorly understood. We find that the endoplasmic reticulum unfolded protein response (UPR) is activated upon exposure to PFTs both in Caenorhabditis elegans and in mammalian cells. Activation of the UPR is protective in vivo against PFTs since animals that lack either the ire-1-xbp-1 or the atf-6 arms of the UPR are more sensitive to PFT than wild-type animals. The UPR acts directly in the cells targeted by the PFT. Loss of the UPR leads to a normal response against unrelated toxins or a pathogenic bacterium, indicating its PFT-protective role is specific. The p38 mitogen-activated protein (MAPK) kinase pathway has been previously shown to be important for cellular defenses against PFTs. We find here that the UPR is one of the key downstream targets of the p38 MAPK pathway in response to PFT since loss of a functional p38 MAPK pathway leads to a failure of PFT to properly activate the ire-1-xbp-1 arm of the UPR. The UPR-mediated activation and response to PFTs is distinct from the canonical UPR-mediated response to unfolded proteins both in terms of its activation and functional sensitivities. These data demonstrate that the UPR, a fundamental intracellular pathway, can operate in intrinsic cellular defenses against bacterial attack.",2008 Oct 10,"['Bischof, Larry J.', 'Kao, Cheng-Yuan', 'Los, Ferdinand C. O.', 'Gonzalez, Manuel R.', 'Shen, Zhouxin', 'Briggs, Steven P.', 'van der Goot, F. Gisou', 'Aroian, Raffi V.']",PLoS Pathog,,,True
b19a29c5c29055c01ee2e63ec63a395c0f7ddb17,PMC,LOMA: A fast method to generate efficient tagged-random primers despite amplification bias of random PCR on pathogens,http://dx.doi.org/10.1186/1471-2105-9-368,PMC2553803,18783594,CC BY,"BACKGROUND: Pathogen detection using DNA microarrays has the potential to become a fast and comprehensive diagnostics tool. However, since pathogen detection chips currently utilize random primers rather than specific primers for the RT-PCR step, bias inherent in random PCR amplification becomes a serious problem that causes large inaccuracies in hybridization signals. RESULTS: In this paper, we study how the efficiency of random PCR amplification affects hybridization signals. We describe a model that predicts the amplification efficiency of a given random primer on a target viral genome. The prediction allows us to filter false-negative probes of the genome that lie in regions of poor random PCR amplification and improves the accuracy of pathogen detection. Subsequently, we propose LOMA, an algorithm to generate random primers that have good amplification efficiency. Wet-lab validation showed that the generated random primers improve the amplification efficiency significantly. CONCLUSION: The blind use of a random primer with attached universal tag (random-tagged primer) in a PCR reaction on a pathogen sample may not lead to a successful amplification. Thus, the design of random-tagged primers is an important consideration when performing PCR.",2008 Sep 10,"['Lee, Wah Heng', 'Wong, Christopher W', 'Leong, Wan Yee', 'Miller, Lance D', 'Sung, Wing Kin']",BMC Bioinformatics,,,True
16627f4c7134394da448b1417a771d13ad7cca4a,PMC,Pandemic influenza in Australia: Using telephone surveys to measure perceptions of threat and willingness to comply,http://dx.doi.org/10.1186/1471-2334-8-117,PMC2556339,18793441,CC BY,"BACKGROUND: Baseline data is necessary for monitoring how a population perceives the threat of pandemic influenza, and perceives how it would behave in the event of pandemic influenza. Our aim was to develop a module of questions for use in telephone health surveys on perceptions of threat of pandemic influenza, and on preparedness to comply with specific public health behaviours in the event of pandemic influenza. METHODS: A module of questions was developed and field tested on 192 adults using the New South Wales Department of Health's in-house Computer Assisted Telephone Interviewing (CATI) facility. The questions were then modified and re field tested on 202 adults. The module was then incorporated into the New South Wales Population Health Survey in the first quarter of 2007. A representative sample of 2,081 adults completed the module. Their responses were weighted against the state population. RESULTS: The reliability of the questions was acceptable with kappa ranging between 0.25 and 0.51. Overall 14.9% of the state population thought pandemic influenza was very or extremely likely to occur; 45.5% were very or extremely concerned that they or their family would be affected by pandemic influenza if it occurred; and 23.8% had made some level of change to the way they live their life because of the possibility of pandemic influenza. In the event of pandemic influenza, the majority of the population were willing to: be vaccinated (75.4%), be isolated (70.2%), and wear a face mask (59.9%). People with higher levels of threat perception are significantly more likely to be willing to comply with specific public health behaviours. CONCLUSION: While only 14.9% of the state population thought pandemic influenza was very or extremely likely to occur, a significantly higher proportion were concerned for self and family should a pandemic actually occur. The baseline data collected in this survey will be useful for monitoring changes over time in the population's perceptions of threat, and preparedness to comply with specific public health behaviours.",2008 Sep 15,"['Barr, Margo', 'Raphael, Beverley', 'Taylor, Melanie', 'Stevens, Garry', 'Jorm, Louisa', 'Giffin, Michael', 'Lujic, Sanja']",BMC Infect Dis,,,True
e5c1960487379bc9bd2cdfef08fc1b6e515abf73,PMC,Composition and Function of Haemolymphatic Tissues in the European Common Shrew,http://dx.doi.org/10.1371/journal.pone.0003413,PMC2561066,18923707,CC BY,"BACKGROUND: Studies of wild animals responding to their native parasites are essential if we are to understand how the immune system functions in the natural environment. While immune defence may bring increased survival, this may come at a resource cost to other physiological traits, including reproduction. Here, we tested the hypothesis that wild common shrews (Sorex araneus), which produce large numbers of offspring during the one breeding season of their short life span, forgo investment in immunity and immune system maintenance, as increased longevity is unlikely to bring further opportunities for mating. In particular, we predicted that adult shrews, with shorter expected lifespans, would not respond as effectively as young animals to infection. METHODOLOGY/PRINCIPAL FINDINGS: We examined haemolymphatic tissues from wild-caught common shrews using light and transmission electron microscopy, applied in conjunction with immunohistology. We compared composition and function of these tissues in shrews of different ages, and the extent and type of inflammatory reactions observed in response to natural parasitic infections. All ages seemed able to mount systemic, specific immune responses, but adult shrews showed some signs of lymphatic tissue exhaustion: lymphatic follicles in adults (n = 21) were both smaller than those in sub-adults (n = 18; Wald = 11.1, p<0.05) and exhibited greater levels of depletion (Wald = 13.3, p<0.05). CONCLUSIONS/SIGNIFICANCE: Contrary to our expectations, shrews respond effectively to their natural parasites, and show little indication of immunosenescence as adults. The pancreas of Aselli, a unique lymphoid organ, may aid in providing efficient immune responses through the storage of large numbers of plasma cells. This may allow older animals to react effectively to previously encountered parasites, but infection by novel agents, and eventual depletion of plasma cell reserves, could both still be factors in the near-synchronous mortality of adult shrews observed shortly after breeding.",2008 Oct 15,"['Bray, Daniel P.', 'Bennett, Malcolm', 'Stockley, Paula', 'Hurst, Jane L.', 'Kipar, Anja']",PLoS One,,,True
daffb9a10450c4d9217cf3819a559c31cd49970c,PMC,Prevention of Cytotoxic T Cell Escape Using a Heteroclitic Subdominant Viral T Cell Determinant,http://dx.doi.org/10.1371/journal.ppat.1000186,PMC2563037,18949029,CC BY,"High affinity antigen-specific T cells play a critical role during protective immune responses. Epitope enhancement can elicit more potent T cell responses and can subsequently lead to a stronger memory pool; however, the molecular basis of such enhancement is unclear. We used the consensus peptide-binding motif for the Major Histocompatibility Complex molecule H-2K(b) to design a heteroclitic version of the mouse hepatitis virus-specific subdominant S598 determinant. We demonstrate that a single amino acid substitution at a secondary anchor residue (Q to Y at position 3) increased the stability of the engineered determinant in complex with H-2K(b). The structural basis for this enhanced stability was associated with local alterations in the pMHC conformation as a result of the Q to Y substitution. Recombinant viruses encoding this engineered determinant primed CTL responses that also reacted to the wildtype epitope with significantly higher functional avidity, and protected against selection of virus mutated at a second CTL determinant and consequent disease progression in persistently infected mice. Collectively, our findings provide a basis for the enhanced immunogenicity of an engineered determinant that will serve as a template for guiding the development of heteroclitic T cell determinants with applications in prevention of CTL escape in chronic viral infections as well as in tumor immunity.",2008 Oct 24,"['Butler, Noah S.', 'Theodossis, Alex', 'Webb, Andrew I.', 'Nastovska, Roza', 'Ramarathinam, Sri Harsha', 'Dunstone, Michelle A.', 'Rossjohn, Jamie', 'Purcell, Anthony W.', 'Perlman, Stanley']",PLoS Pathog,,,True
0951f5ec3710990a5c181e04fa8fdf7d9a0376e5,PMC,HIV-Specific T-Cells Accumulate in the Liver in HCV/HIV Co-Infection,http://dx.doi.org/10.1371/journal.pone.0003454,PMC2565067,18941622,CC BY,"BACKGROUND AND AIMS: Hepatitis C Virus (HCV)-related liver disease progresses more rapidly in individuals co-infected with Human Immunodeficiency Virus-1 (HIV), although the underlying immunologic mechanisms are unknown. We examined whether HIV-specific T-cells are identified in the liver of HCV/HIV co-infected individuals and promote liver inflammation through bystander immune responses. METHODS: Ex-vivo intra-hepatic lymphocytes from HCV mono-infected and HCV/HIV co-infected individuals were assessed for immune responses to HIV and HCV antigens by polychromatic flow cytometry. RESULTS: HCV/HIV liver biopsies had similar frequencies of lymphocytes but lower percentages of CD4(+) T-cells compared to HCV biopsies. In co-infection, intra-hepatic HIV-specific CD8(+) and CD4(+) T-cells producing IFN-γ and TNF-α were detected and were comparable in frequency to those that were HCV-specific. In co-infected individuals, viral-specific CD8(+) T-cells produced more of the fibrogenic cytokine, TNF-α. In both mono- and co-infected individuals, intra-hepatic HCV-specific T-cells were poorly functional compared to HIV-specific T-cells. In co-infection, HAART was not associated with a reconstitution of intra-hepatic CD4(+) T-cells and was associated with reduction in both HIV and HCV-specific intra-hepatic cytokine responses. CONCLUSION: The accumulation of functional HIV-specific T-cells in the liver during HCV/HIV co-infection may represent a bystander role for HIV in inducing faster progression of liver disease.",2008 Oct 20,"['Vali, Bahareh', 'Yue, Feng Yun', 'Jones, R. Brad', 'Sheth, Prameet M.', 'Kaul, Rupert', 'Betts, Michael R.', 'Wong, David', 'Kovacs, Colin', 'Loutfy, Mona', 'Common, Andrew', 'Halpenny, Roberta', 'Ostrowski, Mario A.']",PLoS One,,,True
2a98b0a9e3e89d1aff14a6f64e25374b4e2855a8,PMC,Predicting the sensitivity and specificity of published real-time PCR assays,http://dx.doi.org/10.1186/1476-0711-7-18,PMC2566554,18817537,CC BY,"BACKGROUND: In recent years real-time PCR has become a leading technique for nucleic acid detection and quantification. These assays have the potential to greatly enhance efficiency in the clinical laboratory. Choice of primer and probe sequences is critical for accurate diagnosis in the clinic, yet current primer/probe signature design strategies are limited, and signature evaluation methods are lacking. METHODS: We assessed the quality of a signature by predicting the number of true positive, false positive and false negative hits against all available public sequence data. We found real-time PCR signatures described in recent literature and used a BLAST search based approach to collect all hits to the primer-probe combinations that should be amplified by real-time PCR chemistry. We then compared our hits with the sequences in the NCBI taxonomy tree that the signature was designed to detect. RESULTS: We found that many published signatures have high specificity (almost no false positives) but low sensitivity (high false negative rate). Where high sensitivity is needed, we offer a revised methodology for signature design which may designate that multiple signatures are required to detect all sequenced strains. We use this methodology to produce new signatures that are predicted to have higher sensitivity and specificity. CONCLUSION: We show that current methods for real-time PCR assay design have unacceptably low sensitivities for most clinical applications. Additionally, as new sequence data becomes available, old assays must be reassessed and redesigned. A standard protocol for both generating and assessing the quality of these assays is therefore of great value. Real-time PCR has the capacity to greatly improve clinical diagnostics. The improved assay design and evaluation methods presented herein will expedite adoption of this technique in the clinical lab.",2008 Sep 25,"['Lemmon, Gordon H', 'Gardner, Shea N']",Ann Clin Microbiol Antimicrob,,,True
9f9e925d9999ab39745f2ee8be3efffb5277d082,PMC,Molecular evidence for the evolution of ichnoviruses from ascoviruses by symbiogenesis,http://dx.doi.org/10.1186/1471-2148-8-253,PMC2567993,18801176,CC BY,"BACKGROUND: Female endoparasitic ichneumonid wasps inject virus-like particles into their caterpillar hosts to suppress immunity. These particles are classified as ichnovirus virions and resemble ascovirus virions, which are also transmitted by parasitic wasps and attack caterpillars. Ascoviruses replicate DNA and produce virions. Polydnavirus DNA consists of wasp DNA replicated by the wasp from its genome, which also directs particle synthesis. Structural similarities between ascovirus and ichnovirus particles and the biology of their transmission suggest that ichnoviruses evolved from ascoviruses, although molecular evidence for this hypothesis is lacking. RESULTS: Here we show that a family of unique pox-D5 NTPase proteins in the Glypta fumiferanae ichnovirus are related to three Diadromus pulchellus ascovirus proteins encoded by ORFs 90, 91 and 93. A new alignment technique also shows that two proteins from a related ichnovirus are orthologs of other ascovirus virion proteins. CONCLUSION: Our results provide molecular evidence supporting the origin of ichnoviruses from ascoviruses by lateral transfer of ascoviral genes into ichneumonid wasp genomes, perhaps the first example of symbiogenesis between large DNA viruses and eukaryotic organisms. We also discuss the limits of this evidence through complementary studies, which revealed that passive lateral transfer of viral genes among polydnaviral, bacterial, and wasp genomes may have occurred repeatedly through an intimate coupling of both recombination and replication of viral genomes during evolution. The impact of passive lateral transfers on evolutionary relationships between polydnaviruses and viruses with large double-stranded genomes is considered in the context of the theory of symbiogenesis.",2008 Sep 18,"['Bigot, Yves', 'Samain, Sylvie', 'Augé-Gouillou, Corinne', 'Federici, Brian A']",BMC Evol Biol,,,True
dad72c9c3422ef1c9b9149e8dd567de494d46a8a,PMC,Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice,http://dx.doi.org/10.1371/journal.pone.0003548,PMC2569416,18958172,CC BY,"Pre-existing immunity to human adenovirus serotype 5 (Ad5) is common in the general population. Bypassing pre-existing immunity could maximize Ad5 vaccine efficacy. Vaccination by the intramuscular (I.M.), nasal (I.N.) or oral (P.O.) route with Ad5 expressing Ebola Zaire glycoprotein (Ad5-ZGP) fully protected naïve mice against lethal challenge with Ebola. In the presence of pre-existing immunity, only mice vaccinated I.N. survived. The frequency of IFN-γ+ CD8+ T cells was reduced by 80% and by 15% in animals vaccinated by the I.M. and P.O. routes respectively. Neutralizing antibodies could not be detected in serum from either treatment group. Pre-existing immunity did not compromise the frequency of IFN-γ+ CD8+ T cells (3.9±1% naïve vs. 3.6±1% pre-existing immunity, PEI) nor anti-Ebola neutralizing antibody (NAB, 40±10 reciprocal dilution, both groups). The number of INF-γ+ CD8+ cells detected in bronchioalveolar lavage fluid (BAL) after I.N. immunization was not compromised by pre-existing immunity to Ad5 (146±14, naïve vs. 120±16 SFC/million MNCs, PEI). However, pre-existing immunity reduced NAB levels in BAL by ∼25% in this group. To improve the immune response after oral vaccination, the Ad5-based vaccine was PEGylated. Mice given the modified vaccine did not survive challenge and had reduced levels of IFN-γ+ CD8+ T cells 10 days after administration (0.3±0.3% PEG vs. 1.7±0.5% unmodified). PEGylation did increase NAB levels 2-fold. These results provide some insight about the degree of T and B cell mediated immunity necessary for protection against Ebola virus and suggest that modification of the virus capsid can influence the type of immune response elicited by an Ad5-based vaccine.",2008 Oct 29,"['Croyle, Maria A.', 'Patel, Ami', 'Tran, Kaylie N.', 'Gray, Michael', 'Zhang, Yi', 'Strong, James E.', 'Feldmann, Heinz', 'Kobinger, Gary P.']",PLoS One,,,True
9e716720f4daa4c2f5f85df4b4ee6838255d4f80,PMC,Hantaviruses and TNF-alpha act synergistically to induce ERK1/2 inactivation in Vero E6 cells,http://dx.doi.org/10.1186/1743-422X-5-110,PMC2569924,18822184,CC BY,"BACKGROUND: We have previously reported that the apathogenic Tula hantavirus induces apoptosis in Vero E6 epithelial cells. To assess the molecular mechanisms behind the induced apoptosis we studied the effects of hantavirus infection on cellular signaling pathways which promote cell survival. We previously also observed that the Tula virus-induced cell death process is augmented by external TNF-α. Since TNF-α is involved in the pathogenesis of hantavirus-caused hemorrhagic fever with renal syndrome (HFRS) we investigated its effects on HFRS-causing hantavirus-infected cells. RESULTS: We studied both apathogenic (Tula and Topografov) and pathogenic (Puumala and Seoul) hantaviruses for their ability to regulate cellular signaling pathways and observed a direct virus-mediated down-regulation of external signal-regulated kinases 1 and 2 (ERK1/2) survival pathway activity, which was dramatically enhanced by TNF-α. The fold of ERK1/2 inhibition correlated with viral replication efficiencies, which varied drastically between the hantaviruses studied. CONCLUSION: We demonstrate that in the presence of a cytokine TNF-α, which is increased in HFRS patients, hantaviruses are capable of inactivating proteins that promote cell survival (ERK1/2). These results imply that hantavirus-infected epithelial cell barrier functions might be compromised in diseased individuals and could at least partially explain the mechanisms of renal dysfunction and the resulting proteinuria seen in HFRS patients.",2008 Sep 29,"['Strandin, Tomas', 'Hepojoki, Jussi', 'Wang, Hao', 'Vaheri, Antti', 'Lankinen, Hilkka']",Virol J,,,True
357f5b1caf114fdb8a60870473af88bc9017bf14,PMC,Factors influencing psychological distress during a disease epidemic: Data from Australia's first outbreak of equine influenza,http://dx.doi.org/10.1186/1471-2458-8-347,PMC2571100,18831770,CC BY,"BACKGROUND: In 2007 Australia experienced its first outbreak of highly infectious equine influenza. Government disease control measures were put in place to control, contain, and eradicate the disease; these measures included movement restrictions and quarantining of properties. This study was conducted to assess the psycho-social impacts of this disease, and this paper reports the prevalence of, and factors influencing, psychological distress during this outbreak. METHODS: Data were collected using an online survey, with a link directed to the affected population via a number of industry groups. Psychological distress, as determined by the Kessler 10 Psychological Distress Scale, was the main outcome measure. RESULTS: In total, 2760 people participated in this study. Extremely high levels of non-specific psychological distress were reported by respondents in this study, with 34% reporting high psychological distress (K10 > 22), compared to levels of around 12% in the Australian general population. Analysis, using backward stepwise binary logistic regression analysis, revealed that those living in high risk infection (red) zones (OR = 2.00; 95% CI: 1.57–2.55; p < 0.001) and disease buffer (amber) zones (OR = 1.83; 95% CI: 1.36–2.46; p < 0.001) were at much greater risk of high psychological distress than those living in uninfected (white zones). Although prevalence of high psychological distress was greater in infected EI zones and States, elevated levels of psychological distress were experienced in horse-owners nationally. Statistical analysis indicated that certain groups were more vulnerable to high psychological distress; specifically younger people, and those with lower levels of formal educational qualifications. Respondents whose principal source of income was from horse-related industry were more than twice as likely to have high psychological distress than those whose primary source of income was not linked to horse-related industry (OR = 2.23; 95% CI: 1.82–2.73; p < 0.001). CONCLUSION: Although, methodologically, this study had good internal validity, it has limited generalisability because it was not possible to identify, bound, or sample the target population accurately. However, this study is the first to collect psychological distress data from an affected population during such a disease outbreak and has potential to inform those involved in assessing the potential psychological impacts of human infectious diseases, such as pandemic influenza.",2008 Oct 3,"['Taylor, Melanie R', 'Agho, Kingsley E', 'Stevens, Garry J', 'Raphael, Beverley']",BMC Public Health,,,True
ee0d298d09635c5ae72d4584fba105a705d25afb,PMC,Broadening of Neutralization Activity to Directly Block a Dominant Antibody-Driven SARS-Coronavirus Evolution Pathway,http://dx.doi.org/10.1371/journal.ppat.1000197,PMC2572002,18989460,CC0,"Phylogenetic analyses have provided strong evidence that amino acid changes in spike (S) protein of animal and human SARS coronaviruses (SARS-CoVs) during and between two zoonotic transfers (2002/03 and 2003/04) are the result of positive selection. While several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nAbs) in driving SARS-CoV evolution, particularly during intra-species transmission, is unknown. A detailed examination of SARS-CoV infected animal and human convalescent sera could provide evidence of nAb pressure which, if found, may lead to strategies to effectively block virus evolution pathways by broadening the activity of nAbs. Here we show, by focusing on a dominant neutralization epitope, that contemporaneous- and cross-strain nAb responses against SARS-CoV spike protein exist during natural infection. In vitro immune pressure on this epitope using 2002/03 strain-specific nAb 80R recapitulated a dominant escape mutation that was present in all 2003/04 animal and human viruses. Strategies to block this nAb escape/naturally occurring evolution pathway by generating broad nAbs (BnAbs) with activity against 80R escape mutants and both 2002/03 and 2003/04 strains were explored. Structure-based amino acid changes in an activation-induced cytidine deaminase (AID) “hot spot” in a light chain CDR (complementarity determining region) alone, introduced through shuffling of naturally occurring non-immune human VL chain repertoire or by targeted mutagenesis, were successful in generating these BnAbs. These results demonstrate that nAb-mediated immune pressure is likely a driving force for positive selection during intra-species transmission of SARS-CoV. Somatic hypermutation (SHM) of a single VL CDR can markedly broaden the activity of a strain-specific nAb. The strategies investigated in this study, in particular the use of structural information in combination of chain-shuffling as well as hot-spot CDR mutagenesis, can be exploited to broaden neutralization activity, to improve anti-viral nAb therapies, and directly manipulate virus evolution.",2008 Nov 7,"['Sui, Jianhua', 'Aird, Daniel R.', 'Tamin, Azaibi', 'Murakami, Akikazu', 'Yan, Meiying', 'Yammanuru, Anuradha', 'Jing, Huaiqi', 'Kan, Biao', 'Liu, Xin', 'Zhu, Quan', 'Yuan, Qing-an', 'Adams, Gregory P.', 'Bellini, William J.', 'Xu, Jianguo', 'Anderson, Larry J.', 'Marasco, Wayne A.']",PLoS Pathog,,,True
7ee508ec11743a3ef6f496edaee487e68ace2368,PMC,Influenza A Virus Inhibits Type I IFN Signaling via NF-κB-Dependent Induction of SOCS-3 Expression,http://dx.doi.org/10.1371/journal.ppat.1000196,PMC2572141,18989459,CC BY,"The type I interferon (IFN) system is a first line of defense against viral infections. Viruses have developed various mechanisms to counteract this response. So far, the interferon antagonistic activity of influenza A viruses was mainly observed on the level of IFNβ gene induction via action of the viral non-structural protein 1 (NS1). Here we present data indicating that influenza A viruses not only suppress IFNβ gene induction but also inhibit type I IFN signaling through a mechanism involving induction of the suppressor of cytokine signaling-3 (SOCS-3) protein. Our study was based on the observation that in cells that were infected with influenza A virus and subsequently stimulated with IFNα/β, phosphorylation of the signal transducer and activator of transcription protein 1 (STAT1) was strongly reduced. This impaired STAT1 activation was not due to the action of viral proteins but rather appeared to be induced by accumulation of viral 5′ triphosphate RNA in the cell. SOCS proteins are potent endogenous inhibitors of Janus kinase (JAK)/STAT signaling. Closer examination revealed that SOCS-3 but not SOCS-1 mRNA levels increase in an RNA- and nuclear factor kappa B (NF-κB)-dependent but type I IFN-independent manner early in the viral replication cycle. This direct viral induction of SOCS-3 mRNA and protein expression appears to be relevant for suppression of the antiviral response since in SOCS-3 deficient cells a sustained phosphorylation of STAT1 correlated with elevated expression of type I IFN-dependent genes. As a consequence, progeny virus titers were reduced in SOCS-3 deficient cells or in cells were SOCS-3 expression was knocked-down by siRNA. These data provide the first evidence that influenza A viruses suppress type I IFN signaling on the level of JAK/STAT activation. The inhibitory effect is at least in part due to the induction of SOCS-3 gene expression, which results in an impaired antiviral response.",2008 Nov 7,"['Pauli, Eva-K.', 'Schmolke, Mirco', 'Wolff, Thorsten', 'Viemann, Dorothee', 'Roth, Johannes', 'Bode, Johannes G.', 'Ludwig, Stephan']",PLoS Pathog,,,True
f2af8027b6801850481d09ad0d4c5eb8e31c7d7f,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,True
b8897cea528329455c8e8844a01a5564f34e0e5b,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
66c71e446eadea81cba685fd60bb998990ae6152,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
ceabefd03cf7f09d8c21c9a4a2a784264a6863ab,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
6bfdcf172d10bb3c2e525e7663c65e68ca46f141,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
d22d9e23166f9616aba549098abb323b755b8e7f,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
6d15a3df85701850bd4ebb87f53ca9067e1a9c28,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
57dde8dc0635466830e49cbe6f637f60d2a5548b,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
558daeea8c79f3d8cdbbe23ac1d56dd3880b483a,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
1dafb500595e1264149df72ffc5376c0ddefab27,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
88967166e15bd6cbe70cfd4a3da2fabf467d774a,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
2e677b4ce2466577ae6c79a61e6b8bda482b24b3,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
c70f403fc3480350ea777cc469e5a726154b6ee3,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
0f20ec4a5e8c127bd73cc8fe068f7b3968109671,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
d2b4782c75bfa05865a5f3191614a20dcd1f38a5,PMC,The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics,http://dx.doi.org/10.1371/journal.pgen.1000251,PMC2572142,18989457,CC0,"The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Φ(ST) = 0.92; nDNA F (ST) = 0.18), and reduced gene flow, which, along with large differences in sero-prevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (∼324,000–169,000 years ago), which expanded during the Late Pleistocene (∼100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (∼14,000–7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.",2008 Nov 7,"['Antunes, Agostinho', 'Troyer, Jennifer L.', 'Roelke, Melody E.', 'Pecon-Slattery, Jill', 'Packer, Craig', 'Winterbach, Christiaan', 'Winterbach, Hanlie', 'Hemson, Graham', 'Frank, Laurence', 'Stander, Philip', 'Siefert, Ludwig', 'Driciru, Margaret', 'Funston, Paul J.', 'Alexander, Kathy A.', 'Prager, Katherine C.', 'Mills, Gus', 'Wildt, David', 'Bush, Mitch', ""O'Brien, Stephen J."", 'Johnson, Warren E.']",PLoS Genet,,,False
ca2a9474b1355a82b175767d68aaba4995e60681,PMC,Seeking Membranes: Positive-Strand RNA Virus Replication Complexes,http://dx.doi.org/10.1371/journal.pbio.0060270,PMC2573941,18959488,CC BY,How much do we really understand about how +RNA viruses usurp and transform the intracellular architecture of host cells when they replicate?,2008 Oct 28,"Denison, Mark R",PLoS Biol,,,True
3ee10f61fbf042f0e6c1f90b5e26a1199c13f177,PMC,Could FIV zoonosis responsible of the breakdown of the pathocenosis which has reduced the European CCR5-Delta32 allele frequencies?,http://dx.doi.org/10.1186/1743-422X-5-119,PMC2575341,18925940,CC BY,"BACKGROUND: In Europe, the north-south downhill cline frequency of the chemokine receptor CCR5 allele with a 32-bp deletion (CCR5-Δ32) raises interesting questions for evolutionary biologists. We had suggested first that, in the past, the European colonizers, principally Romans, might have been instrumental of a progressively decrease of the frequencies southwards. Indeed, statistical analyses suggested strong negative correlations between the allele frequency and historical parameters including the colonization dates by Mediterranean civilisations. The gene flows from colonizers to native populations were extremely low but colonizers are responsible of the spread of several diseases suggesting that the dissemination of parasites in naive populations could have induced a breakdown rupture of the fragile pathocenosis changing the balance among diseases. The new equilibrium state has been reached through a negative selection of the null allele. RESULTS: Most of the human diseases are zoonoses and cat might have been instrumental in the decrease of the allele frequency, because its diffusion through Europe was a gradual process, due principally to Romans; and that several cat zoonoses could be transmitted to man. The possible implication of a feline lentivirus (FIV) which does not use CCR5 as co-receptor is discussed. This virus can infect primate cells in vitro and induces clinical signs in macaque. Moreover, most of the historical regions with null or low frequency of CCR5-Δ32 allele coincide with historical range of the wild felid species which harbor species-specific FIVs. CONCLUSION: We proposed the hypothesis that the actual European CCR5 allelic frequencies are the result of a negative selection due to a disease spreading. A cat zoonosis, could be the most plausible hypothesis. Future studies could provide if CCR5 can play an antimicrobial role in FIV pathogenesis. Moreover, studies of ancient DNA could provide more evidences regarding the implications of zoonoses in the actual CCR5-Δ32 distribution.",2008 Oct 16,"Faure, Eric",Virol J,,,True
9c33102dc55e225f5836f9cf9c9d5f5b918820d8,PMC,Key Role of Splenic Myeloid DCs in the IFN-αβ Response to Adenoviruses In Vivo,http://dx.doi.org/10.1371/journal.ppat.1000208,PMC2576454,19008951,CC BY,"The early systemic production of interferon (IFN)-αβ is an essential component of the antiviral host defense mechanisms, but is also thought to contribute to the toxic side effects accompanying gene therapy with adenoviral vectors. Here we investigated the IFN-αβ response to human adenoviruses (Ads) in mice. By comparing the responses of normal, myeloid (m)DC- and plasmacytoid (p)DC-depleted mice and by measuring IFN-αβ mRNA expression in different organs and cells types, we show that in vivo, Ads elicit strong and rapid IFN-αβ production, almost exclusively in splenic mDCs. Using knockout mice, various strains of Ads (wild type, mutant and UV-inactivated) and MAP kinase inhibitors, we demonstrate that the Ad-induced IFN-αβ response does not require Toll-like receptors (TLR), known cytosolic sensors of RNA (RIG-I/MDA-5) and DNA (DAI) recognition and interferon regulatory factor (IRF)-3, but is dependent on viral endosomal escape, signaling via the MAP kinase SAPK/JNK and IRF-7. Furthermore, we show that Ads induce IFN-αβ and IL-6 in vivo by distinct pathways and confirm that IFN-αβ positively regulates the IL-6 response. Finally, by measuring TNF-α responses to LPS in Ad-infected wild type and IFN-αβR(−/−) mice, we show that IFN-αβ is the key mediator of Ad-induced hypersensitivity to LPS. These findings indicate that, like endosomal TLR signaling in pDCs, TLR-independent virus recognition in splenic mDCs can also produce a robust early IFN-αβ response, which is responsible for the bulk of IFN-αβ production induced by adenovirus in vivo. The signaling requirements are different from known TLR-dependent or cytosolic IFN-αβ induction mechanisms and suggest a novel cytosolic viral induction pathway. The hypersensitivity to components of the microbial flora and invading pathogens may in part explain the toxic side effects of adenoviral gene therapy and contribute to the pathogenesis of adenoviral disease.",2008 Nov 14,"['Fejer, György', 'Drechsel, Lisa', 'Liese, Jan', 'Schleicher, Ulrike', 'Ruzsics, Zsolt', 'Imelli, Nicola', 'Greber, Urs F.', 'Keck, Simone', 'Hildenbrand, Bernd', 'Krug, Anne', 'Bogdan, Christian', 'Freudenberg, Marina A.']",PLoS Pathog,,,True
312f1e49512a7626113891f7796d4c2c318c7e39,PMC,Genetic immunization with Hantavirus vaccine combining expression of G2 glycoprotein and fused interleukin-2,http://dx.doi.org/10.1186/1479-0556-6-15,PMC2577087,18940009,CC BY,"In this research, we developed a novel chimeric HTNV-IL-2-G2 DNA vaccine plasmid by genetically linking IL-2 gene to the G2 segment DNA and tested whether it could be a candidate vaccine. Chimeric gene was first expressed in eukaryotic expression system pcDNA3.1 (+). The HTNV-IL-2-G2 expressed a 72 kDa fusion protein in COS-7 cells. Meanwhile, the fusion protein kept the activity of its parental proteins. Furthermore, BALB/c mice were vaccinated by the chimeric gene. ELISA, cell microculture neutralization test in vitro were used to detect the humoral immune response in immunized BALB/c mice. Lymphocyte proliferation assay was used to detect the cellular immune response.- The results showed that the chimeric gene could simultaneously evoke specific antibody against G2 glycoprotein and IL-2. And the immunized mice of every group elicited neutralizing antibodies with different titers. Lymphocyte proliferation assay results showed that the stimulation indexes of splenocytes of chimeric gene to G2 and IL-2 were significantly higher than that of other groups. Our results suggest that IL-2-based HTNV G2 DNA can induce both humoral and cellular immune response specific for HTNV G2 and can be a candidate DNA vaccine for HTNV infection.",2008 Oct 22,"['Hao, Huang', 'Xiu, Li', 'Zehua, Zhang', 'Min, Jia', 'Hongbo, Hu', 'Zhihong, Wu', 'Zhenhua, Zhu', 'Xiaohong, Wan', 'Hanju, Huang']",Genet Vaccines Ther,,,True
9f7ed2037968c63fa97eb6fc7c35e9738a654541,PMC,Gender difference in knowledge of tuberculosis and associated health-care seeking behaviors: a cross-sectional study in a rural area of China,http://dx.doi.org/10.1186/1471-2458-8-354,PMC2577657,18842127,CC BY,"BACKGROUND: Tuberculosis (TB) detection under the national TB control program in China follows passive case-finding guidelines, which could be influenced by the accessibility of health service and patient's health-care seeking behaviors. One intriguing topic is the correlation between men and women's knowledge on TB and their health-care seeking behaviors. METHODS: Two cross-sectional studies were separately carried out in Yangzhong County, a rural area of China. One study, by using systematic sampling method, including 1,200 subjects, was conducted to investigate the TB knowledge among general population. Another study in the same source population screened 33,549 people aged 15 years or over among 20 stratified cluster-sampled villages for identifying prolonged cough patients at households and individual interviews were then carried out. Gender difference in the knowledge of TB and health-care seeking behaviors was analyzed particularly. RESULTS: Among general population, only 16.0% (men 17.1% vs. women 15.0%) knew the prolonged cough with the duration of 3 weeks or longer was a symptom for suspicious TB. Fewer women than men knew the local appointed health facility for TB diagnosis and treatment as well as the current free TB service policy. Moreover, women were less likely to learn information about TB and share it with others on their own initiatives. On the contrary, after the onset of the prolonged cough, women (79.2%) were more likely to seek health-care than men (58.6%) did. However, a large part of women preferred to visit the lower level non-hospital health facilities at first such as village clinics and drugstores. CONCLUSION: TB and DOTS program were not well known by rural Chinese. Gender issues should be considered to reduce diagnostic delay of TB and improve both men and women's access to qualified health facility for TB care. Strengthening awareness of TB and improving the accessibility of health-care service is essential in TB control strategy, especially under the current vertical TB control system.",2008 Oct 8,"['Wang, Jianming', 'Fei, Yang', 'Shen, Hongbing', 'Xu, Biao']",BMC Public Health,,,True
de707f97b534ca340482600ed1f008b20d7b1b8e,PMC,Procalcitonin levels in acute exacerbation of COPD admitted in ICU: a prospective cohort study,http://dx.doi.org/10.1186/1471-2334-8-145,PMC2577677,18947382,CC BY,"BACKGROUND: Antibiotics are recommended for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to intensive care units (ICU). Serum procalcitonin (PCT) could be a useful tool for selecting patients with a lower probability of developing bacterial infection, but its measurement has not been investigated in this population. METHODS: We conducted a single center prospective cohort study in consecutive COPD patients admitted to the ICU for AECOPD between September 2005 and September 2006. Sputum samples or tracheal aspirates were tested for the presence of bacteria and viruses. PCT levels were measured at the time of admittance, six hours, and 24 hours using a sensitive immunoassay. RESULTS: Thirty nine AECOPD patients were included, 31 of which (79%) required a ventilator support at admission. The median [25%–75% interquartile range] PCT level, assessed in 35/39 patients, was: 0.096 μg/L [IQR, 0.065 to 0.178] at the time of admission, 0.113 μg/L [IQR, 0.074 to 0.548] at six hours, and 0.137 μg/L [IQR, 0.088 to 0.252] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 μg/L in 14/35 (40%) patients and more than 0.25 μg/L in 10/35 (29%) patients, suggesting low and high probability of bacterial infection, respectively. Five species of bacteria and nine species of viruses were detected in 12/39 (31%) patients. Among the four patients positive for Pseudomonas aeruginosa, one had a PCTmax less than 0.25 μg/L and three had a PCTmax less than 0.1 μg/L. The one patient positive for Haemophilus influenzae had a PCTmax more than 0.25 μg/L. The presence or absence of viruses did not influence PCT at time of admission (0.068 vs 0.098 μg/L respectively, P = 0.80). CONCLUSION: The likelihood of bacterial infection is low among COPD patients admitted to ICU for AECOPD (40% with PCT < 0.1 μg/L) suggesting a possible inappropriate use of antibiotics. Further studies are necessary to assess the impact of a procalcitonin-based therapeutic strategy in critically ill COPD patients.",2008 Oct 23,"['Daubin, Cédric', 'Parienti, Jean-Jacques', 'Vabret, Astrid', 'Ramakers, Michel', 'Fradin, Sabine', 'Terzi, Nicolas', 'Freymuth, François', 'Charbonneau, Pierre', 'du Cheyron, Damien']",BMC Infect Dis,,,True
1ff38c46bce64adb553080443f72ff90e61dcbc3,PMC,Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates,http://dx.doi.org/10.1371/journal.ppat.1000225,PMC2582959,19043556,CC0,"Ebola virus (EBOV) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV) is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVΔG/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). All six animals showed no evidence of illness associated with the VSVΔG/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV.",2008 Nov 28,"['Geisbert, Thomas W.', 'Daddario-DiCaprio, Kathleen M.', 'Lewis, Mark G.', 'Geisbert, Joan B.', 'Grolla, Allen', 'Leung, Anders', 'Paragas, Jason', 'Matthias, Lennox', 'Smith, Mark A.', 'Jones, Steven M.', 'Hensley, Lisa E.', 'Feldmann, Heinz', 'Jahrling, Peter B.']",PLoS Pathog,,,True
0ab32c7726deaff1ef10c2ee762c2cb917d92929,PMC,Identification and Characterization of a New Orthoreovirus from Patients with Acute Respiratory Infections,http://dx.doi.org/10.1371/journal.pone.0003803,PMC2583042,19030226,CC BY,"First discovered in the early 1950s, reoviruses (respiratory enteric orphan viruses) were not associated with any known disease, and hence named orphan viruses. Recently, our group reported the isolation of the Melaka virus from a patient with acute respiratory disease and provided data suggesting that this new orthoreovirus is capable of human-to-human transmission and is probably of bat origin. Here we report yet another Melaka-like reovirus (named Kampar virus) isolated from the throat swab of a 54 year old male patient in Kampar, Perak, Malaysia who was suffering from high fever, acute respiratory disease and vomiting at the time of virus isolation. Serological studies indicated that Kampar virus was transmitted from the index case to at least one other individual and caused respiratory disease in the contact case. Sequence analysis of the four small class genome segments indicated that Kampar and Melaka viruses are closely related. This was confirmed by virus neutralization assay, showing an effective two-way cross neutralization, i.e., the serum against one virus was able to neutralize the other. Although the exact origin of Kampar virus is unknown, epidemiological tracing revealed that the house of the index case is surrounded by fruit trees frequently visited by fruit bats. There is a high probability that Kampar virus originated from bats and was transmitted to humans via bat droppings or contaminated fruits. The discovery of Kampar virus highlights the increasing trend of emergence of bat zoonotic viruses and the need to expand our understanding of bats as a source of many unknown viruses.",2008 Nov 25,"['Chua, Kaw Bing', 'Voon, Kenny', 'Crameri, Gary', 'Tan, Hui Siu', 'Rosli, Juliana', 'McEachern, Jennifer A.', 'Suluraju, Sivagami', 'Yu, Meng', 'Wang, Lin-Fa']",PLoS One,,,True
727602c6861782ad9eb87bfff3fc6824b7008af5,PMC,Widespread distribution and a new recombinant species of Brazilian virus associated with cotton blue disease,http://dx.doi.org/10.1186/1743-422X-5-123,PMC2583970,18937850,CC BY,"BACKGROUND: Cotton blue disease (CBD), an important global cotton crop pathology responsible for major economic losses, is prevalent in the major cotton-producing states of Brazil. Typical CBD symptoms include stunting due to internodal shortening, leaf rolling, intense green foliage, and yellowing veins. Atypical CBD symptoms, including reddish and withered leaves, were also observed in Brazilian cotton fields in 2007. Recently, a Polerovirus named Cotton leafroll dwarf virus (CLRDV) was shown to be associated with CBD. RESULTS: To understand the distribution and genetic diversity of CLRDV in Brazil, we analyzed 23 CBD-symptomatic plants from susceptible cotton varieties originating from five of the six most important cotton-growing states, from 2004–2007. Here, we report on CLRDV diversity in plants with typical or atypical CBD symptoms by comparing viral coat protein, RNA polymerase (RdRp), and intergenic region genomic sequences. CONCLUSION: The virus had a widespread distribution with a low genetic diversity; however, three divergent isolates were associated with atypical CBD symptoms. These divergent isolates had a CLRDV-related coat protein but a distinct RdRp sequence, and probably arose from recombination events. Based on the taxonomic rules for the family Luteoviridae, we propose that these three isolates represent isolates of a new species in the genus Polerovirus.",2008 Oct 20,"['Silva, TF', 'Corrêa, RL', 'Castilho, Y', 'Silvie, P', 'Bélot, J-L', 'Vaslin, MFS']",Virol J,,,True
36885622f4e863ce69c521612093f1682fed1a5d,PMC,The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile,http://dx.doi.org/10.1186/1755-8794-1-54,PMC2584050,18950519,CC BY,"BACKGROUND: Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints. METHODS: Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides) was used for validation. RESULTS: By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (p < 0.01). Multimarker clustering showed two distinctive proteomic profiles independent of age and ethnicity. Eighteen of 19 cancer samples clustered together (sensitivity 95%) while 27/36 of non-cancer samples clustered in a second group. Nine non-cancer samples that clustered with cancer samples included 5 pre-malignant lesions (1 adenomatous polyp and 4 intestinal metaplasia). Validation using a second sample set showed the sensitivity and specificity to be 88% and 93%, respectively. Positive predictive value of the combined data was 0.80. Selected peptide sequencing identified pepsinogen C and pepsin A activation peptide as significantly down-regulated and alpha-defensin as significantly up-regulated. CONCLUSION: This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.",2008 Oct 25,"['Kon, Oi Lian', 'Yip, Tai-Tung', 'Ho, Meng Fatt', 'Chan, Weng Hoong', 'Wong, Wai Keong', 'Tan, Soo Yong', 'Ng, Wai Har', 'Kam, Siok Yuen', 'Eng, Alvin KH', 'Ho, Patrick', 'Viner, Rosa', 'Ong, Hock Soo', 'Kumarasinghe, M Priyanthi']",BMC Med Genomics,,,True
1a5bdcd1c259d4b40800f9e96219641aafd5f6b9,PMC,Type I feline coronavirus spike glycoprotein fails to recognize aminopeptidase N as a functional receptor on feline cell lines,http://dx.doi.org/10.1099/vir.0.82666-0,PMC2584236,17485536,CC BY,"There are two types of feline coronaviruses that can be distinguished by serology and sequence analysis. Type I viruses, which are prevalent in the field but are difficult to isolate and propagate in cell culture, and type II viruses, which are less prevalent but replicate well in cell culture. An important determinant of coronavirus infection, in vivo and in cell culture, is the interaction of the virus surface glycoprotein with a cellular receptor. It is generally accepted that feline aminopeptidase N can act as a receptor for the attachment and entry of type II strains, and it has been proposed that the same molecule acts as a receptor for type I viruses. However, the experimental data are inconclusive. The aim of the studies reported here was to provide evidence for or against the involvement of feline aminopeptidase N as a receptor for type I feline coronaviruses. Our approach was to produce retroviral pseudotypes that bear the type I or type II feline coronavirus surface glycoprotein and to screen a range of feline cell lines for the expression of a functional receptor for attachment and entry. Our results show that type I feline coronavirus surface glycoprotein fails to recognize feline aminopeptidase N as a functional receptor on three continuous feline cell lines. This suggests that feline aminopeptidase N is not a receptor for type I feline coronaviruses. Our results also indicate that it should be possible to use retroviral pseudotypes to identify and characterize the cellular receptor for type I feline coronaviruses.",2007 Jun,"['Dye, Charlotte', 'Temperton, Nigel', 'Siddell, Stuart G.']",J Gen Virol,,,True
8e9e154ec04f065cca2b000ebc1e86239ef11c54,PMC,Type I feline coronavirus spike glycoprotein fails to recognize aminopeptidase N as a functional receptor on feline cell lines,http://dx.doi.org/10.1099/vir.0.82666-0,PMC2584236,17485536,CC BY,"There are two types of feline coronaviruses that can be distinguished by serology and sequence analysis. Type I viruses, which are prevalent in the field but are difficult to isolate and propagate in cell culture, and type II viruses, which are less prevalent but replicate well in cell culture. An important determinant of coronavirus infection, in vivo and in cell culture, is the interaction of the virus surface glycoprotein with a cellular receptor. It is generally accepted that feline aminopeptidase N can act as a receptor for the attachment and entry of type II strains, and it has been proposed that the same molecule acts as a receptor for type I viruses. However, the experimental data are inconclusive. The aim of the studies reported here was to provide evidence for or against the involvement of feline aminopeptidase N as a receptor for type I feline coronaviruses. Our approach was to produce retroviral pseudotypes that bear the type I or type II feline coronavirus surface glycoprotein and to screen a range of feline cell lines for the expression of a functional receptor for attachment and entry. Our results show that type I feline coronavirus surface glycoprotein fails to recognize feline aminopeptidase N as a functional receptor on three continuous feline cell lines. This suggests that feline aminopeptidase N is not a receptor for type I feline coronaviruses. Our results also indicate that it should be possible to use retroviral pseudotypes to identify and characterize the cellular receptor for type I feline coronaviruses.",2007 Jun,"['Dye, Charlotte', 'Temperton, Nigel', 'Siddell, Stuart G.']",J Gen Virol,,,False
0d80c3f53b8900bb8d958492553dc052c2b3c628,PMC,The role of interleukin-12 in the heavy metal-elicited immunomodulation: relevance of various evaluation methods,http://dx.doi.org/10.1186/1745-6673-3-25,PMC2585571,18990205,CC BY,"BACKGROUND: Increasing evidence exists that heavy metals modulate T helper cell (Th) responses and thereby elicit various pathological manifestation. Interleukin (IL)-12, a crucial innate cytokine, was found to be regulated by such xenobiotic agents. This study aimed at testing whether IL-12 profiles may be indicative of heavy metals-induced immunomodulation. METHODS: Human immunocompetent cells, activated either by monoclonal antibodies or heat-killed Salmonella enterica, were cultured in the absence or presence of cadmium (Cd) acetate or mercuric (Hg) chloride. In vivo experiments were set up where BALB/c mice were exposed to sub-lethal doses of Cd or Hg salts for 3 or 5 weeks. Cytotoxicity was assessed by MTT-reduction assay. Modulation of cytokine profiles was evaluated by enzyme-linked immunosorbent assay (ELISA), cytometric bead-based array (CBA) and real-time polymerase chain reaction (RT-PCR); the relevance of these methods of cytokine quantification was explored. RESULTS: Modulation of IL-12 profiles in Cd- or Hg-exposed human PBMC was dose-dependent and significantly related to IFN-γ levels as well as to the Th1- or Th2-polarized responses. Similarly, skewing the Th1/Th2 ratios in vivo correlated significantly with up- or down-regulation of IL-12 levels in both cases of investigated metals. CONCLUSION: It can be inferred that: (i) IL-12 profiles alone may represent a relevant indicator of heavy metal-induced immune modulation; (ii) evaluating cytokine profiles by CBA is relevant and can adequately replace other methods such as ELISA and RT-PCR in basic research as well as in immune diagnostics; and (iii) targeting IL-12 in therapeutic approaches may be promising to modify Th1/Th2-associated immune disorders.",2008 Nov 6,"Hemdan, Nasr YA",J Occup Med Toxicol,,,True
eec9198400dee7d7ec27088377bced55c01a126a,PMC,Immune Mechanisms Responsible for Vaccination against and Clearance of Mucosal and Lymphatic Norovirus Infection,http://dx.doi.org/10.1371/journal.ppat.1000236,PMC2587711,19079577,CC BY,"Two cardinal manifestations of viral immunity are efficient clearance of acute infection and the capacity to vaccinate against secondary viral exposure. For noroviruses, the contributions of T cells to viral clearance and vaccination have not been elucidated. We report here that both CD4 and CD8 T cells are required for efficient clearance of primary murine norovirus (MNV) infection from the intestine and intestinal lymph nodes. Further, long-lasting protective immunity was generated by oral live virus vaccination. Systemic vaccination with the MNV capsid protein also effectively protected against mucosal challenge, while vaccination with the capsid protein of the distantly related human Lordsdale virus provided partial protection. Fully effective vaccination required a broad immune response including CD4 T cells, CD8 T cells, and B cells, but the importance of specific immune cell types varied between the intestine and intestinal lymph nodes. Perforin, but not interferon gamma, was required for clearance of MNV infection by adoptively transferred T lymphocytes from vaccinated hosts. These studies prove the feasibility of both mucosal and systemic vaccination against mucosal norovirus infection, demonstrate tissue specificity of norovirus immune cells, and indicate that efficient vaccination strategies should induce potent CD4 and CD8 T cell responses.",2008 Dec 12,"['Chachu, Karen A.', 'LoBue, Anna D.', 'Strong, David W.', 'Baric, Ralph S.', 'Virgin, Herbert W.']",PLoS Pathog,,,True
6825e9b1b3377b18ec3725a954b15d2760603a28,PMC,MyD88 Is Required for Protection from Lethal Infection with a Mouse-Adapted SARS-CoV,http://dx.doi.org/10.1371/journal.ppat.1000240,PMC2587915,19079579,CC BY,"A novel human coronavirus, SARS-CoV, emerged suddenly in 2003, causing approximately 8000 human cases and more than 700 deaths worldwide. Since most animal models fail to faithfully recapitulate the clinical course of SARS-CoV in humans, the virus and host factors that mediate disease pathogenesis remain unclear. Recently, our laboratory and others developed a recombinant mouse-adapted SARS-CoV (rMA15) that was lethal in BALB/c mice. In contrast, intranasal infection of young 10-week-old C57BL/6 mice with rMA15 results in a nonlethal infection characterized by high titer replication within the lungs, lung inflammation, destruction of lung tissue, and loss of body weight, thus providing a useful model to identify host mediators of protection. Here, we report that mice deficient in MyD88 (MyD88(−/−)), an adapter protein that mediates Toll-like receptor (TLR), IL-1R, and IL-18R signaling, are far more susceptible to rMA15 infection. The genetic absence of MyD88 resulted in enhanced pulmonary pathology and greater than 90% mortality by day 6 post-infection. MyD88(−/−) mice had significantly higher viral loads in lung tissue throughout the course of infection. Despite increased viral loads, the expression of multiple proinflammatory cytokines and chemokines within lung tissue and recruitment of inflammatory monocytes/macrophages to the lung was severely impaired in MyD88(−/−) mice compared to wild-type mice. Furthermore, mice deficient in chemokine receptors that contribute to monocyte recruitment to the lung were more susceptible to rMA15-induced disease and exhibited severe lung pathology similar to that seen in MyD88(−/−)mice. These data suggest that MyD88-mediated innate immune signaling and inflammatory cell recruitment to the lung are required for protection from lethal rMA15 infection.",2008 Dec 12,"['Sheahan, Timothy', 'Morrison, Thomas E.', 'Funkhouser, William', 'Uematsu, Satoshi', 'Akira, Shizou', 'Baric, Ralph S.', 'Heise, Mark T.']",PLoS Pathog,,,True
fbcfed5be85b5356dd0d103c8b6ab37296035cf5,PMC,Avian Influenza: a global threat needing a global solution,http://dx.doi.org/10.1186/1447-056X-7-5,PMC2588555,19014538,CC BY,"There have been three influenza pandemics since the 1900s, of which the 1919–1919 flu pandemic had the highest mortality rates. The influenza virus infects both humans and birds, and mutates using two mechanisms: antigenic drift and antigenic shift. Currently, the H5N1 avian flu virus is limited to outbreaks among poultry and persons in direct contact to infected poultry, but the mortality rate among infected humans is high. Avian influenza (AI) is endemic in Asia as a result of unregulated poultry rearing in rural areas. Such birds often live in close proximity to humans and this increases the chance of genetic re-assortment between avian and human influenza viruses which may produce a mutant strain that is easily transmitted between humans. Once this happens, a global pandemic is likely. Unlike SARS, a person with influenza infection is contagious before the onset of case-defining symptoms which limits the effectiveness of case isolation as a control strategy. Researchers have shown that carefully orchestrated of public health measures could potentially limit the spread of an AI pandemic if implemented soon after the first cases appear. To successfully contain and control an AI pandemic, both national and global strategies are needed. National strategies include source surveillance and control, adequate stockpiles of anti-viral agents, timely production of flu vaccines and healthcare system readiness. Global strategies such as early integrated response, curbing the disease outbreak at source, utilization of global resources, continuing research and open communication are also critical.",2008 Nov 13,"['Koh, GCH', 'Wong, TY', 'Cheong, SK', 'Koh, DSQ']",Asia Pac Fam Med,,,True
635bc39e204a9e098961ccaef51d67e83226b07e,PMC,"Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection",http://dx.doi.org/10.1186/1742-2094-5-48,PMC2588578,18947414,CC BY,"BACKGROUND: Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. METHODS: To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. RESULTS: Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap), effects on host cell protein processing (ubiquitin ligase), synapse remodeling (Complement 1q), and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection) and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease). Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of Sylvius and hippocampus, CD4+ and CD8+ T cells, and activated microglia in perivascular areas and brain parenchyma. Genetically resistant, chronically infected mice had substantially less inflammation. CONCLUSION: In outbred mice, chronic, adult acquired T. gondii infection causes neurologic and behavioral abnormalities secondary to inflammation and loss of brain parenchyma. Perivascular inflammation is prominent particularly contiguous to the aqueduct of Sylvius and hippocampus. Even resistant mice have perivascular inflammation. This mouse model of chronic T. gondii infection raises questions of whether persistence of this parasite in brain can cause inflammation or neurodegeneration in genetically susceptible hosts.",2008 Oct 23,"['Hermes, Gretchen', 'Ajioka, James W', 'Kelly, Krystyna A', 'Mui, Ernest', 'Roberts, Fiona', 'Kasza, Kristen', 'Mayr, Thomas', 'Kirisits, Michael J', 'Wollmann, Robert', 'Ferguson, David JP', 'Roberts, Craig W', 'Hwang, Jong-Hee', 'Trendler, Toria', 'Kennan, Richard P', 'Suzuki, Yasuhiro', 'Reardon, Catherine', 'Hickey, William F', 'Chen, Lieping', 'McLeod, Rima']",J Neuroinflammation,,,True
26670350d15f4a1f0a7072ad985d98b21c28fd5a,PMC,Self-Interest versus Group-Interest in Antiviral Control,http://dx.doi.org/10.1371/journal.pone.0001558,PMC2592701,19050769,CC BY,"Antiviral agents have been hailed to hold considerable promise for the treatment and prevention of emerging viral diseases like H5N1 avian influenza and SARS. However, antiviral drugs are not completely harmless, and the conditions under which individuals are willing to participate in a large-scale antiviral drug treatment program are as yet unknown. We provide population dynamical and game theoretical analyses of large-scale prophylactic antiviral treatment programs. Throughout we compare the antiviral control strategy that is optimal from the public health perspective with the control strategy that would evolve if individuals make their own, rational decisions. To this end we investigate the conditions under which a large-scale antiviral control program can prevent an epidemic, and we analyze at what point in an unfolding epidemic the risk of infection starts to outweigh the cost of antiviral treatment. This enables investigation of how the optimal control strategy is moulded by the efficacy of antiviral drugs, the risk of mortality by antiviral prophylaxis, and the transmissibility of the pathogen. Our analyses show that there can be a strong incentive for an individual to take less antiviral drugs than is optimal from the public health perspective. In particular, when public health asks for early and aggressive control to prevent or curb an emerging pathogen, for the individual antiviral drug treatment is attractive only when the risk of infection has become non-negligible. It is even possible that from a public health perspective a situation in which everybody takes antiviral drugs is optimal, while the process of individual choice leads to a situation where nobody is willing to take antiviral drugs.",2008 Feb 13,"['van Boven, Michiel', 'Klinkenberg, Don', 'Pen, Ido', 'Weissing, Franz J.', 'Heesterbeek, Hans']",PLoS One,,,True
6a8a9b70b5eac41b7aebe94c6ed55930696aac59,PMC,Self-Interest versus Group-Interest in Antiviral Control,http://dx.doi.org/10.1371/journal.pone.0001558,PMC2592701,19050769,CC BY,"Antiviral agents have been hailed to hold considerable promise for the treatment and prevention of emerging viral diseases like H5N1 avian influenza and SARS. However, antiviral drugs are not completely harmless, and the conditions under which individuals are willing to participate in a large-scale antiviral drug treatment program are as yet unknown. We provide population dynamical and game theoretical analyses of large-scale prophylactic antiviral treatment programs. Throughout we compare the antiviral control strategy that is optimal from the public health perspective with the control strategy that would evolve if individuals make their own, rational decisions. To this end we investigate the conditions under which a large-scale antiviral control program can prevent an epidemic, and we analyze at what point in an unfolding epidemic the risk of infection starts to outweigh the cost of antiviral treatment. This enables investigation of how the optimal control strategy is moulded by the efficacy of antiviral drugs, the risk of mortality by antiviral prophylaxis, and the transmissibility of the pathogen. Our analyses show that there can be a strong incentive for an individual to take less antiviral drugs than is optimal from the public health perspective. In particular, when public health asks for early and aggressive control to prevent or curb an emerging pathogen, for the individual antiviral drug treatment is attractive only when the risk of infection has become non-negligible. It is even possible that from a public health perspective a situation in which everybody takes antiviral drugs is optimal, while the process of individual choice leads to a situation where nobody is willing to take antiviral drugs.",2008 Feb 13,"['van Boven, Michiel', 'Klinkenberg, Don', 'Pen, Ido', 'Weissing, Franz J.', 'Heesterbeek, Hans']",PLoS One,,,False
6783ff6a7398428f7a6bb894d39c44746b85cf73,PMC,A quality assessment of genetic association studies supporting susceptibility and outcome in acute lung injury,http://dx.doi.org/10.1186/cc7098,PMC2592769,18950526,CC BY,"INTRODUCTION: Clinical observations and animal models provide evidence that the development of acute lung injury (ALI), a phenomenon of acute diffuse lung inflammation in critically ill patients, is influenced by genetic factors. Association studies are the main tool for exploring common genetic variations underlying ALI susceptibility and/or outcome. We aimed to assess the quality of positive genetic association studies with ALI susceptibility and/or outcome in adults in order to highlight their consistency and major limitations. METHODS: We conducted a broad PubMed literature search from 1996 to June 2008 for original articles in English supporting a positive association (P ≤ 0.05) of genetic variants contributing to all-cause ALI susceptibility and/or outcome. Studies were evaluated based on current recommendations using a 10-point quality scoring system derived from 14 criteria, and the gene was considered as the unit of replication. Genes were also categorized according to biological processes using the Gene Ontology. RESULTS: Our search identified a total of 29 studies reporting positive findings for 16 genes involved mainly in the response to external stimulus and cell signal transduction. The genes encoding for interleukin-6, mannose-binding lectin, surfactant protein B, and angiotensin-converting enzyme were the most replicated across the studies. On average, the studies had an intermediate quality score (median of 4.62 and interquartile range of 3.33 to 6.15). CONCLUSIONS: Although the quality of association studies seems to have improved over the years, more and better designed studies, including the replication of previous findings, with larger sample sizes extended to population groups other than those of European descent, are needed for identifying firm genetic modifiers of ALI.",2008 Oct 25,"['Flores, Carlos', 'del Mar Pino-Yanes, Maria', 'Villar, Jesús']",Crit Care,,,True
25e0a5092935b57609da913715f5e1e5e6ecb91f,PMC,Plaque assay for human coronavirus NL63 using human colon carcinoma cells,http://dx.doi.org/10.1186/1743-422X-5-138,PMC2603006,19014487,CC BY,"BACKGROUND: Coronaviruses cause a broad range of diseases in animals and humans. Human coronavirus (hCoV) NL63 is associated with up to 10% of common colds. Viral plaque assays enable the characterization of virus infectivity and allow for purifying virus stock solutions. They are essential for drug screening. Hitherto used cell cultures for hCoV-NL63 show low levels of virus replication and weak and diffuse cytopathogenic effects. It has not yet been possible to establish practicable plaque assays for this important human pathogen. RESULTS: 12 different cell cultures were tested for susceptibility to hCoV-NL63 infection. Human colon carcinoma cells (CaCo-2) replicated virus more than 100 fold more efficiently than commonly used African green monkey kidney cells (LLC-MK2). CaCo-2 cells showed cytopathogenic effects 4 days post infection. Avicel, agarose and carboxymethyl-cellulose overlays proved suitable for plaque assays. Best results were achieved with Avicel, which produced large and clear plaques from the 4(th )day of infection. The utility of plaque assays with agrose overlay was demonstrated for purifying virus, thereby increasing viral infectivity by 1 log 10 PFU/mL. CONCLUSION: CaCo-2 cells support hCoV-NL63 better than LLC-MK2 cells and enable cytopathogenic plaque assays. Avicel overlay is favourable for plaque quantification, and agarose overlay is preferred for plaque purification. HCoV-NL63 virus stock of increased infectivity will be beneficial in antiviral screening, animal modelling of disease, and other experimental tasks.",2008 Nov 12,"['Herzog, Petra', 'Drosten, Christian', 'Müller, Marcel A']",Virol J,,,True
b41f3634a764bf08cbc4588f37d7d422a02fa541,PMC,Development and evaluation of a leadership training program for public health emergency response: results from a Chinese study,http://dx.doi.org/10.1186/1471-2458-8-377,PMC2605461,18973664,CC BY,"BACKGROUND: Since the 9/11 attack and severe acute respiratory syndrome (SARS), the development of qualified and able public health leaders has become a new urgency in building the infrastructure needed to address public health emergencies. Although previous studies have reported that the training of individual leaders is an important approach, the systemic and scientific training model need further improvement and development. The purpose of this study was to develop, deliver, and evaluate a participatory leadership training program for emergency response. METHODS: Forty-one public health leaders (N = 41) from five provinces completed the entire emergency preparedness training program in China. The program was evaluated by anonymous questionnaires and semi-structured interviews held prior to training, immediately post-training and 12-month after training (Follow-up). RESULTS: The emergency preparedness training resulted in positive shifts in knowledge, self-assessment of skills for public health leaders. More than ninety-five percent of participants reported that the training model was scientific and feasible. Moreover, the response of participants in the program to the avian influenza outbreak, as well as the planned evaluations for this leadership training program, further demonstrated both the successful approaches and methods and the positive impact of this integrated leadership training initiative. CONCLUSION: The emergency preparedness training program met its aims and objectives satisfactorily, and improved the emergency capability of public health leaders. This suggests that the leadership training model was effective and feasible in improving the emergency preparedness capability.",2008 Oct 30,"['Wang, Chongjian', 'Wei, Sheng', 'Xiang, Hao', 'Wu, Jing', 'Xu, Yihua', 'Liu, Li', 'Nie, Shaofa']",BMC Public Health,,,True
0a41b85153ef8a084f7b3476d4d38832f533e914,PMC,Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference,http://dx.doi.org/10.1371/journal.pone.0004118,PMC2606062,19122813,CC BY,"BACKGROUND: Equine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causes respiratory disease, neurological disorders and abortions. The virus is a significant equine pathogen, but current EHV-1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interfering RNAs (siRNA's), delivered intranasally, could prove a valuable alternative for infection control. siRNA's against two essential EHV-1 genes, encoding the viral helicase (Ori) and glycoprotein B, were evaluated for their potential to decrease EHV-1 infection in a mouse model. METHODOLOGY/PRINCIPAL FNDINGS: siRNA therapy in vitro significantly reduced virus production and plaque size. Viral titers were reduced 80-fold with 37.5 pmol of a single siRNA or with as little as 6.25 pmol of each siRNA when used in combination. siRNA therapy in vivo significantly reduced viral replication and clinical signs. Intranasal treatment did not require a transport vehicle and proved effective when given up to 12 h before or after infection. CONCLUSIONS/SIGNIFICANCE: siRNA treatment has potential for both prevention and early treatment of EHV-1 infections.",2009 Jan 5,"['Fulton, Amy', 'Peters, Sarah T.', 'Perkins, Gillian A.', 'Jarosinski, Keith W.', 'Damiani, Armando', 'Brosnahan, Margaret', 'Buckles, Elizabeth L.', 'Osterrieder, Nikolaus', 'Van de Walle, Gerlinde R.']",PLoS One,,,True
9693080ead2c95fe79e8bf077637b5585cac664f,PMC,Resequencing microarray probe design for typing genetically diverse viruses: human rhinoviruses and enteroviruses,http://dx.doi.org/10.1186/1471-2164-9-577,PMC2607299,19046445,CC BY,"BACKGROUND: Febrile respiratory illness (FRI) has a high impact on public health and global economics and poses a difficult challenge for differential diagnosis. A particular issue is the detection of genetically diverse pathogens, i.e. human rhinoviruses (HRV) and enteroviruses (HEV) which are frequent causes of FRI. Resequencing Pathogen Microarray technology has demonstrated potential for differential diagnosis of several respiratory pathogens simultaneously, but a high confidence design method to select probes for genetically diverse viruses is lacking. RESULTS: Using HRV and HEV as test cases, we assess a general design strategy for detecting and serotyping genetically diverse viruses. A minimal number of probe sequences (26 for HRV and 13 for HEV), which were potentially capable of detecting all serotypes of HRV and HEV, were determined and implemented on the Resequencing Pathogen Microarray RPM-Flu v.30/31 (Tessarae RPM-Flu). The specificities of designed probes were validated using 34 HRV and 28 HEV strains. All strains were successfully detected and identified at least to species level. 33 HRV strains and 16 HEV strains could be further differentiated to serotype level. CONCLUSION: This study provides a fundamental evaluation of simultaneous detection and differential identification of genetically diverse RNA viruses with a minimal number of prototype sequences. The results demonstrated that the newly designed RPM-Flu v.30/31 can provide comprehensive and specific analysis of HRV and HEV samples which implicates that this design strategy will be applicable for other genetically diverse viruses.",2008 Dec 1,"['Wang, Zheng', 'Malanoski, Anthony P', 'Lin, Baochuan', 'Kidd, Carolyn', 'Long, Nina C', 'Blaney, Kate M', 'Thach, Dzung C', 'Tibbetts, Clark', 'Stenger, David A']",BMC Genomics,,,True
e63eaf2a9904a7212185d87824ddd187ab110272,PMC,The expression and antigenicity of a truncated spike-nucleocapsid fusion protein of severe acute respiratory syndrome-associated coronavirus,http://dx.doi.org/10.1186/1471-2180-8-207,PMC2613400,19038059,CC BY,"BACKGROUND: In the absence of effective drugs, controlling SARS relies on the rapid identification of cases and appropriate management of the close contacts, or effective vaccines for SARS. Therefore, developing specific and sensitive laboratory tests for SARS as well as effective vaccines are necessary for national authorities. RESULTS: Genes encoding truncated nucleocapsid (N) and spike (S) proteins of SARSCoV were cloned into the expression vector pQE30 and fusionally expressed in Escherichia coli M15. The fusion protein was analyzed for reactivity with SARS patients' sera and with anti-sera against the two human coronaviruses HCoV 229E and HCoV OC43 by ELISA, IFA and immunoblot assays. Furthermore, to evaluate the antigen-specific humoral antibody and T-cell responses in mice, the fusion protein was injected into 6-week-old BALB/c mice and a neutralization test as well as a T-cell analysis was performed. To evaluate the antiviral efficacy of immunization, BALB/c mice were challenged intranasally with SARSCoV at day 33 post injection and viral loads were determined by fluorescent quantitative RT-PCR. Serological results showed that the diagnostic sensitivity and specificity of the truncated S-N fusion protein derived the SARS virus were > 99% (457/460) and 100.00% (650/650), respectively. Furthermore there was no cross-reactivity with other two human coronaviruses. High titers of antibodies to SRASCoV appeared in the immunized mice and the neutralization test showed that antibodies to the fusion protein could inhibit SARSCoV. The T cell proliferation showed that the fusion protein could induce an antigen-specific T-cell response. Fluorescent quantitative RT-PCR showed that BALB/c mice challenged intranasally with SARSCoV at day 33 post injection were completely protected from virus replication. CONCLUSION: The truncated S-N fusion protein is a suitable immunodiagnostic antigen and vaccine candidate.",2008 Nov 28,"['Mu, Feng', 'Niu, Dongsheng', 'Mu, Jingsong', 'He, Bo', 'Han, Weiguo', 'Fan, Baoxing', 'Huang, Shengyong', 'Qiu, Yan', 'You, Bo', 'Chen, Weijun']",BMC Microbiol,,,True
c4fc28f1a66e4664a3dc12f5b121ee97aa9f122d,PMC,A Novel Replication-Competent Vaccinia Vector MVTT Is Superior to MVA for Inducing High Levels of Neutralizing Antibody via Mucosal Vaccination,http://dx.doi.org/10.1371/journal.pone.0004180,PMC2613559,19159014,CC BY,"Mucosal vaccination offers great advantage for inducing protective immune response to prevent viral transmission and dissemination. Here, we report our findings of a head-to-head comparison of two viral vectors modified vaccinia Ankara (MVA) and a novel replication-competent modified vaccinia Tian Tan (MVTT) for inducing neutralizing antibodies (Nabs) via intramuscular and mucosal vaccinations in mice. MVTT is an attenuated variant of the wild-type VTT, which was historically used as a smallpox vaccine for millions of Chinese people. The spike glycoprotein (S) of SARS-CoV was used as the test antigen after the S gene was constructed in the identical genomic location of two vectors to generate vaccine candidates MVTT-S and MVA-S. Using identical doses, MVTT-S induced lower levels (∼2-3-fold) of anti- SARS-CoV neutralizing antibodies (Nabs) than MVA-S through intramuscular inoculation. MVTT-S, however, was capable of inducing consistently 20-to-100-fold higher levels of Nabs than MVA-S when inoculated via either intranasal or intraoral routes. These levels of MVTT-S-induced Nab responses were substantially (∼10-fold) higher than that induced via the intramuscular route in the same experiments. Moreover, pre-exposure to the wild-type VTT via intranasal or intraoral route impaired the Nab response via the same routes of MVTT-S vaccination probably due to the pre-existing anti-VTT Nab response. The efficacy of intranasal or intraoral vaccination, however, was still 20-to-50-fold better than intramuscular inoculation despite the subcutaneous pre-exposure to wild-type VTT. Our data have implications for people who maintain low levels of anti-VTT Nabs after historical smallpox vaccination. MVTT is therefore an attractive live viral vector for mucosal vaccination.",2009 Jan 13,"['Huang, Xiaoxing', 'Lu, Bin', 'Yu, Wenbo', 'Fang, Qing', 'Liu, Li', 'Zhuang, Ke', 'Shen, Tingting', 'Wang, Haibo', 'Tian, Po', 'Zhang, Linqi', 'Chen, Zhiwei']",PLoS One,,,True
eb83b27bafc37b40794c2c7cc1b921cbcdb4138c,PMC,Augmented Lung Inflammation Protects against Influenza A Pneumonia,http://dx.doi.org/10.1371/journal.pone.0004176,PMC2613561,19137067,CC BY,"BACKGROUND: Influenza pneumonia causes high mortality every year, and pandemic episodes kill millions of people. Influenza-related mortality has been variously ascribed to an ineffective host response that fails to limit viral replication, an excessive host inflammatory response that results in lung injury and impairment of gas exchange, or to bacterial superinfection. We sought to determine whether lung inflammation promoted or impaired host survival in influenza pneumonia. METHODS AND FINDINGS: To distinguish among these possible causes of influenza-related death, we induced robust lung inflammation by exposing mice to an aerosolized bacterial lysate prior to challenge with live virus. The treatment induced expression of the inflammatory cytokines IL-6 and TNF in bronchoalveolar lavage fluid 8- and 40-fold greater, respectively, than that caused by lethal influenza infection. Yet, this augmented inflammation was associated with striking resistance to host mortality (0% vs 90% survival, p = 0.0001) and reduced viral titers (p = 0.004). Bacterial superinfection of virus infected lungs was not observed. When mice were repeatedly exposed to the bacterial lysate, as would be clinically desirable during an influenza epidemic, there was no tachyphylaxis of the induced viral resistance. When the bacterial lysate was administered after the viral challenge, there was still some mortality benefit, and when ribavirin was added to the aerosolized bacterial lysate, host survival was synergistically improved (0% vs 93.3% survival, p<0.0001). CONCLUSIONS: Together, these data indicate that innate immune resistance to influenza can be effectively stimulated, and suggest that ineffective rather than excessive inflammation is the major cause of mortality in influenza pneumonia.",2009 Jan 12,"['Tuvim, Michael J.', 'Evans, Scott E.', 'Clement, Cecilia G.', 'Dickey, Burton F.', 'Gilbert, Brian E.']",PLoS One,,,True
b5f778aafd8e2a94701f7398641519a2041ab303,PMC,The impact of SARS on hospital performance,http://dx.doi.org/10.1186/1472-6963-8-228,PMC2613902,18990210,CC BY,"BACKGROUND: During the SARS epidemic, healthcare utilization and medical services decreased significantly. However, the long-term impact of SARS on hospital performance needs to be further discussed. METHODS: A municipal hospital in Taipei City was shut down for a month due to SARS and then became the designated SARS and infectious disease hospital for the city. This study collected the outpatient, inpatient and emergency service volumes for every year from April to March over four years. Average monthly service amount ± standard deviation were used to compare patient volume for the whole hospital, as well as the outpatient numbers accessing different departments. The ARIMA model of outpatient volume in the pre-SARS year was developed. RESULTS: The average monthly service volume of outpatient visits for the base year 2002 was 52317 ± 4204 visits per month, and number for 2003 and the following two years were 55%, 82% and 84% of the base year respectively. The average emergency service volume was 4382 ± 356 visits per month at the base year and this became 45%, 77% and 87% of the base year for the following three years respectively. Average inpatient service volume was 8520 ± 909 inpatient days per month at the base year becoming 43%, 81% and 87% of the base year for the following three years respectively. Only the emergency service volume had recovered to the level of a non-significant difference at the second year after SARS. In addition, the departments of family medicine, metabolism and nephrology reached the 2002 patient number in 2003. The ARIMA (2,1,0) model was the most suitable for outpatient volume in pre-SARS year. The MAPE of the ARIMA (2,1,0) model for the pre-SARS year was 6.9%, and 43.2%, 10.6%, 6.2% for following 3 years. CONCLUSION: This study demonstrates that if a hospital is completely shut down due to SARS or a similar disease, the impact is longer than previous reported and different departments may experience different recover periods. The findings of this study identify subspecialties that are particularly vulnerable in an infectious disease designated hospital and such hospitals need to consider which subspecialties should be included in their medical structure.",2008 Nov 6,"['Chu, Dachen', 'Chen, Ran-Chou', 'Ku, Chia-Yu', 'Chou, Pesus']",BMC Health Serv Res,,,True
323c52cddef7a35732afdc41dac2a1aa6cb60f16,PMC,"Bayesian, Maximum Parsimony and UPGMA Models for Inferring the Phylogenies of Antelopes Using Mitochondrial Markers",,PMC2614192,19204824,CC BY,"This investigation was aimed to compare the inference of antelope phylogenies resulting from the 16S rRNA, cytochrome-b (cyt-b) and d-loop segments of mitochondrial DNA using three different computational models including Bayesian (BA), maximum parsimony (MP) and unweighted pair group method with arithmetic mean (UPGMA). The respective nucleotide sequences of three Oryx species (Oryx leucoryx, Oryx dammah and Oryx gazella) and an out-group (Addax nasomaculatus) were aligned and subjected to BA, MP and UPGMA models for comparing the topologies of respective phylogenetic trees. The 16S rRNA region possessed the highest frequency of conserved sequences (97.65%) followed by cyt-b (94.22%) and d-loop (87.29%). There were few transitions (2.35%) and none transversions in 16S rRNA as compared to cyt-b (5.61% transitions and 0.17% transversions) and d-loop (11.57% transitions and 1.14% transversions) while comparing the four taxa. All the three mitochondrial segments clearly differentiated the genus Addax from Oryx using the BA or UPGMA models. The topologies of all the gamma-corrected Bayesian trees were identical irrespective of the marker type. The UPGMA trees resulting from 16S rRNA and d-loop sequences were also identical (Oryx dammah grouped with Oryx leucoryx) to Bayesian trees except that the UPGMA tree based on cyt-b showed a slightly different phylogeny (Oryx dammah grouped with Oryx gazella) with a low bootstrap support. However, the MP model failed to differentiate the genus Addax from Oryx. These findings demonstrate the efficiency and robustness of BA and UPGMA methods for phylogenetic analysis of antelopes using mitochondrial markers.",2008 Oct 6,"['Khan, Haseeb A.', 'Arif, Ibrahim A.', 'Bahkali, Ali H.', 'Al Farhan, Ahmad H.', 'Al Homaidan, Ali A.']",Evol Bioinform Online,,,True
18e4bf7e0c2d81caa5795174a4f25d5a035e09b1,PMC,A Novel Peptide Enhances Therapeutic Efficacy of Liposomal Anti-Cancer Drugs in Mice Models of Human Lung Cancer,http://dx.doi.org/10.1371/journal.pone.0004171,PMC2614347,19137069,CC BY,"Lung cancer is the leading cause of cancer-related mortality worldwide. The lack of tumor specificity remains a major drawback for effective chemotherapies and results in dose-limiting toxicities. However, a ligand-mediated drug delivery system should be able to render chemotherapy more specific to tumor cells and less toxic to normal tissues. In this study, we isolated a novel peptide ligand from a phage-displayed peptide library that bound to non-small cell lung cancer (NSCLC) cell lines. The targeting phage bound to several NSCLC cell lines but not to normal cells. Both the targeting phage and the synthetic peptide recognized the surgical specimens of NSCLC with a positive rate of 75% (27 of 36 specimens). In severe combined immunodeficiency (SCID) mice bearing NSCLC xenografts, the targeting phage specifically bound to tumor masses. The tumor homing ability of the targeting phage was inhibited by the cognate synthetic peptide, but not by a control or a WTY-mutated peptide. When the targeting peptide was coupled to liposomes carrying doxorubicin or vinorelbine, the therapeutic index of the chemotherapeutic agents and the survival rates of mice with human lung cancer xenografts markedly increased. Furthermore, the targeting liposomes increased drug accumulation in tumor tissues by 5.7-fold compared with free drugs and enhanced cancer cell apoptosis resulting from a higher concentration of bioavailable doxorubicin. The current study suggests that this tumor-specific peptide may be used to create chemotherapies specifically targeting tumor cells in the treatment of NSCLC and to design targeted gene transfer vectors or it may be used one in the diagnosis of this malignancy.",2009 Jan 12,"['Chang, De-Kuan', 'Lin, Chin-Tarng', 'Wu, Chien-Hsun', 'Wu, Han-Chung']",PLoS One,,,True
c63c4d58d170136b8d3b5a66424b5ac3f73a92d9,PMC,Viral Discovery and Sequence Recovery Using DNA Microarrays,http://dx.doi.org/10.1371/journal.pbio.0000002,PMC261870,14624234,CC BY,"Because of the constant threat posed by emerging infectious diseases and the limitations of existing approaches used to identify new pathogens, there is a great demand for new technological methods for viral discovery. We describe herein a DNA microarray-based platform for novel virus identification and characterization. Central to this approach was a DNA microarray designed to detect a wide range of known viruses as well as novel members of existing viral families; this microarray contained the most highly conserved 70mer sequences from every fully sequenced reference viral genome in GenBank. During an outbreak of severe acute respiratory syndrome (SARS) in March 2003, hybridization to this microarray revealed the presence of a previously uncharacterized coronavirus in a viral isolate cultivated from a SARS patient. To further characterize this new virus, approximately 1 kb of the unknown virus genome was cloned by physically recovering viral sequences hybridized to individual array elements. Sequencing of these fragments confirmed that the virus was indeed a new member of the coronavirus family. This combination of array hybridization followed by direct viral sequence recovery should prove to be a general strategy for the rapid identification and characterization of novel viruses and emerging infectious disease.",2003 Nov 17,"['Wang, David', 'Urisman, Anatoly', 'Liu, Yu-Tsueng', 'Springer, Michael', 'Ksiazek, Thomas G', 'Erdman, Dean D', 'Mardis, Elaine R', 'Hickenbotham, Matthew', 'Magrini, Vincent', 'Eldred, James', 'Latreille, J. Phillipe', 'Wilson, Richard K', 'Ganem, Don', 'DeRisi, Joseph L']",PLoS Biol,,,True
23b1f3033a86c0f53ee90b9ba14634e956f8610b,PMC,"IL-1β, IL-6, and RANTES as Biomarkers of Chikungunya Severity",http://dx.doi.org/10.1371/journal.pone.0004261,PMC2625438,19156204,CC BY,"BACKGROUND: Little is known about the immunopathogenesis of Chikungunya virus. Circulating levels of immune mediators and growth factors were analyzed from patients infected during the first Singaporean Chikungunya fever outbreak in early 2008 to establish biomarkers associated with infection and/or disease severity. METHODS AND FINDINGS: Adult patients with laboratory-confirmed Chikungunya fever infection, who were referred to the Communicable Disease Centre/Tan Tock Seng Hospital during the period from January to February 2008, were included in this retrospective study. Plasma fractions were analyzed using a multiplex-microbead immunoassay. Among the patients, the most common clinical features were fever (100%), arthralgia (90%), rash (50%) and conjunctivitis (40%). Profiles of 30 cytokines, chemokines, and growth factors were able to discriminate the clinical forms of Chikungunya from healthy controls, with patients classified as non-severe and severe disease. Levels of 8 plasma cytokines and 4 growth factors were significantly elevated. Statistical analysis showed that an increase in IL-1β, IL-6 and a decrease in RANTES were associated with disease severity. CONCLUSIONS: This is the first comprehensive report on the production of cytokines, chemokines, and growth factors during acute Chikungunya virus infection. Using these biomarkers, we were able to distinguish between mild disease and more severe forms of Chikungunya fever, thus enabling the identification of patients with poor prognosis and monitoring of the disease.",2009 Jan 21,"['Ng, Lisa F. P.', 'Chow, Angela', 'Sun, Yong-Jiang', 'Kwek, Dyan J. C.', 'Lim, Poh-Lian', 'Dimatatac, Frederico', 'Ng, Lee-Ching', 'Ooi, Eng-Eong', 'Choo, Khar-Heng', 'Her, Zhisheng', 'Kourilsky, Philippe', 'Leo, Yee-Sin']",PLoS One,,,True
672ae4f77f6a2cc3358bfe1e492c268e2dbe3d7a,PMC,Direct Metagenomic Detection of Viral Pathogens in Nasal and Fecal Specimens Using an Unbiased High-Throughput Sequencing Approach,http://dx.doi.org/10.1371/journal.pone.0004219,PMC2625441,19156205,CC BY,"With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a “next-generation” parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1–0.25 ml of nasopharyngeal aspirates (N = 3) and fecal specimens (N = 5), and more than 10 µg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298–32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome–derived, 20–460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484–15,260 reads of norovirus sequence (78–98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures.",2009 Jan 19,"['Nakamura, Shota', 'Yang, Cheng-Song', 'Sakon, Naomi', 'Ueda, Mayo', 'Tougan, Takahiro', 'Yamashita, Akifumi', 'Goto, Naohisa', 'Takahashi, Kazuo', 'Yasunaga, Teruo', 'Ikuta, Kazuyoshi', 'Mizutani, Tetsuya', 'Okamoto, Yoshiko', 'Tagami, Michihira', 'Morita, Ryoji', 'Maeda, Norihiro', 'Kawai, Jun', 'Hayashizaki, Yoshihide', 'Nagai, Yoshiyuki', 'Horii, Toshihiro', 'Iida, Tetsuya', 'Nakaya, Takaaki']",PLoS One,,,True
702a827446e87746c8cd4a843ec2fcf0d306d102,PMC,Direct Metagenomic Detection of Viral Pathogens in Nasal and Fecal Specimens Using an Unbiased High-Throughput Sequencing Approach,http://dx.doi.org/10.1371/journal.pone.0004219,PMC2625441,19156205,CC BY,"With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a “next-generation” parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1–0.25 ml of nasopharyngeal aspirates (N = 3) and fecal specimens (N = 5), and more than 10 µg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298–32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome–derived, 20–460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484–15,260 reads of norovirus sequence (78–98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures.",2009 Jan 19,"['Nakamura, Shota', 'Yang, Cheng-Song', 'Sakon, Naomi', 'Ueda, Mayo', 'Tougan, Takahiro', 'Yamashita, Akifumi', 'Goto, Naohisa', 'Takahashi, Kazuo', 'Yasunaga, Teruo', 'Ikuta, Kazuyoshi', 'Mizutani, Tetsuya', 'Okamoto, Yoshiko', 'Tagami, Michihira', 'Morita, Ryoji', 'Maeda, Norihiro', 'Kawai, Jun', 'Hayashizaki, Yoshihide', 'Nagai, Yoshiyuki', 'Horii, Toshihiro', 'Iida, Tetsuya', 'Nakaya, Takaaki']",PLoS One,,,False
957f2e312b2e2b190e6a2a2b623ecd4b9d4d85ed,PMC,Direct Metagenomic Detection of Viral Pathogens in Nasal and Fecal Specimens Using an Unbiased High-Throughput Sequencing Approach,http://dx.doi.org/10.1371/journal.pone.0004219,PMC2625441,19156205,CC BY,"With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a “next-generation” parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1–0.25 ml of nasopharyngeal aspirates (N = 3) and fecal specimens (N = 5), and more than 10 µg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298–32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome–derived, 20–460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484–15,260 reads of norovirus sequence (78–98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures.",2009 Jan 19,"['Nakamura, Shota', 'Yang, Cheng-Song', 'Sakon, Naomi', 'Ueda, Mayo', 'Tougan, Takahiro', 'Yamashita, Akifumi', 'Goto, Naohisa', 'Takahashi, Kazuo', 'Yasunaga, Teruo', 'Ikuta, Kazuyoshi', 'Mizutani, Tetsuya', 'Okamoto, Yoshiko', 'Tagami, Michihira', 'Morita, Ryoji', 'Maeda, Norihiro', 'Kawai, Jun', 'Hayashizaki, Yoshihide', 'Nagai, Yoshiyuki', 'Horii, Toshihiro', 'Iida, Tetsuya', 'Nakaya, Takaaki']",PLoS One,,,False
df813efa8268b627ab35cc9920d201fe70f45a03,PMC,Direct Metagenomic Detection of Viral Pathogens in Nasal and Fecal Specimens Using an Unbiased High-Throughput Sequencing Approach,http://dx.doi.org/10.1371/journal.pone.0004219,PMC2625441,19156205,CC BY,"With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a “next-generation” parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1–0.25 ml of nasopharyngeal aspirates (N = 3) and fecal specimens (N = 5), and more than 10 µg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298–32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome–derived, 20–460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484–15,260 reads of norovirus sequence (78–98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures.",2009 Jan 19,"['Nakamura, Shota', 'Yang, Cheng-Song', 'Sakon, Naomi', 'Ueda, Mayo', 'Tougan, Takahiro', 'Yamashita, Akifumi', 'Goto, Naohisa', 'Takahashi, Kazuo', 'Yasunaga, Teruo', 'Ikuta, Kazuyoshi', 'Mizutani, Tetsuya', 'Okamoto, Yoshiko', 'Tagami, Michihira', 'Morita, Ryoji', 'Maeda, Norihiro', 'Kawai, Jun', 'Hayashizaki, Yoshihide', 'Nagai, Yoshiyuki', 'Horii, Toshihiro', 'Iida, Tetsuya', 'Nakaya, Takaaki']",PLoS One,,,False
418d9b50173b09a1dc9f31d77b539213b63cb9ea,PMC,Direct Metagenomic Detection of Viral Pathogens in Nasal and Fecal Specimens Using an Unbiased High-Throughput Sequencing Approach,http://dx.doi.org/10.1371/journal.pone.0004219,PMC2625441,19156205,CC BY,"With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a “next-generation” parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1–0.25 ml of nasopharyngeal aspirates (N = 3) and fecal specimens (N = 5), and more than 10 µg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298–32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome–derived, 20–460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484–15,260 reads of norovirus sequence (78–98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures.",2009 Jan 19,"['Nakamura, Shota', 'Yang, Cheng-Song', 'Sakon, Naomi', 'Ueda, Mayo', 'Tougan, Takahiro', 'Yamashita, Akifumi', 'Goto, Naohisa', 'Takahashi, Kazuo', 'Yasunaga, Teruo', 'Ikuta, Kazuyoshi', 'Mizutani, Tetsuya', 'Okamoto, Yoshiko', 'Tagami, Michihira', 'Morita, Ryoji', 'Maeda, Norihiro', 'Kawai, Jun', 'Hayashizaki, Yoshihide', 'Nagai, Yoshiyuki', 'Horii, Toshihiro', 'Iida, Tetsuya', 'Nakaya, Takaaki']",PLoS One,,,False
e4d4fde9df50047757fa69030407e861748c0eb3,PMC,Complete genomic sequence analysis of infectious bronchitis virus Ark DPI strain and its evolution by recombination,http://dx.doi.org/10.1186/1743-422X-5-157,PMC2628353,19102764,CC BY,"An infectious bronchitis virus Arkansas DPI (Ark DPI) virulent strain was sequenced, analyzed and compared with many different IBV strains and coronaviruses. The genome of Ark DPI consists of 27,620 nucleotides, excluding poly (A) tail, and comprises ten open reading frames. Comparative sequence analysis of Ark DPI with other IBV strains shows striking similarity to the Conn, Gray, JMK, and Ark 99, which were circulating during that time period. Furthermore, comparison of the Ark genome with other coronaviruses demonstrates a close relationship to turkey coronavirus. Among non-structural genes, the 5'untranslated region (UTR), 3C-like proteinase (3CL(pro)) and the polymerase (RdRp) sequences are 100% identical to the Gray strain. Among structural genes, S1 has 97% identity with Ark 99; S2 has 100% identity with JMK and 96% to Conn; 3b 99%, and 3C to N is 100% identical to Conn strain. Possible recombination sites were found at the intergenic region of spike gene, 3'end of S1 and 3a gene. Independent recombination events may have occurred in the entire genome of Ark DPI, involving four different IBV strains, suggesting that genomic RNA recombination may occur in any part of the genome at number of sites. Hence, we speculate that the Ark DPI strain originated from the Conn strain, but diverged and evolved independently by point mutations and recombination between field strains.",2008 Dec 22,"['Ammayappan, Arun', 'Upadhyay, Chitra', 'Gelb, Jack', 'Vakharia, Vikram N']",Virol J,,,True
859085c2184a2ca5829809632648e1c80c725d2b,PMC,"Sequence space coverage, entropy of genomes and the potential to detect non-human DNA in human samples",http://dx.doi.org/10.1186/1471-2164-9-509,PMC2628393,18973670,CC BY,"BACKGROUND: Genomes store information for building and maintaining organisms. Complete sequencing of many genomes provides the opportunity to study and compare global information properties of those genomes. RESULTS: We have analyzed aspects of the information content of Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Saccharomyces cerevisiae, and Escherichia coli (K-12) genomes. Virtually all possible (> 98%) 12 bp oligomers appear in vertebrate genomes while < 2% of 19 bp oligomers are present. Other species showed different ranges of > 98% to < 2% of possible oligomers in D. melanogaster (12–17 bp), C. elegans (11–17 bp), A. thaliana (11–17 bp), S. cerevisiae (10–16 bp) and E. coli (9–15 bp). Frequencies of unique oligomers in the genomes follow similar patterns. We identified a set of 2.6 M 15-mers that are more than 1 nucleotide different from all 15-mers in the human genome and so could be used as probes to detect microbes in human samples. In a human sample, these probes would detect 100% of the 433 currently fully sequenced prokaryotes and 75% of the 3065 fully sequenced viruses. The human genome is significantly more compact in sequence space than a random genome. We identified the most frequent 5- to 20-mers in the human genome, which may prove useful as PCR primers. We also identified a bacterium, Anaeromyxobacter dehalogenans, which has an exceptionally low diversity of oligomers given the size of its genome and its GC content. The entropy of coding regions in the human genome is significantly higher than non-coding regions and chromosomes. However chromosomes 1, 2, 9, 12 and 14 have a relatively high proportion of coding DNA without high entropy, and chromosome 20 is the opposite with a low frequency of coding regions but relatively high entropy. CONCLUSION: Measures of the frequency of oligomers are useful for designing PCR assays and for identifying chromosomes and organisms with hidden structure that had not been previously recognized. This information may be used to detect novel microbes in human tissues.",2008 Oct 30,"['Liu, Zhandong', 'Venkatesh, Santosh S', 'Maley, Carlo C']",BMC Genomics,,,True
aba67455b71206b20d9b978e994cb571392dd404,PMC,"Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells",http://dx.doi.org/10.1186/1479-5876-6-78,PMC2628881,19077207,CC BY,"Members of the carcinoembryonic antigen family (CEACAMs) are widely expressed, and, depending on the tissue, capable of regulating diverse functions including tumor promotion, tumor suppression, angiogenesis, and neutrophil activation. Four members of this family, CEACAM1, CEACAM8, CEACAM6, and CEACAM3 (recognized by CD66a, CD66b, CD66c, and CD66d mAbs, respectively), are expressed on human neutrophils. CD66a, CD66b, CD66c, and CD66d antibodies each increase neutrophil adhesion to human umbilical vein endothelial cell monolayers. This increase in neutrophil adhesion caused by CD66 antibodies is blocked by CD18 mAbs and is associated with upregulation of CD11/CD18 on the neutrophil surface. To examine potential interactions of CEACAMs in neutrophil signaling, the effects on neutrophil adhesion to human umbilical vein endothelial cells of a set of CD66 mAbs was tested following desensitization to stimulation by various combinations of these mAbs. Addition of a CD66 mAb in the absence of calcium results in desensitization of neutrophils to stimulation by that CD66 mAb. The current data show that desensitization of neutrophils to any two CEACAMs results in selective desensitization to those two CEACAMs, while the cells remain responsive to the other two neutrophil CEACAMs. In addition, cells desensitized to CEACAM-3, -6, and -8 were still responsive to stimulation of CEACAM1 by CD66a mAbs. In contrast, desensitization of cells to CEACAM1 and any two of the other CEACAMs left the cells unresponsive to all CD66 mAbs. Cells desensitized to any combination of CEACAMs remained responsive to the unrelated control protein CD63. Thus, while there is significant independence of the four neutrophil CEACAMs in signaling, CEACAM1 appears to play a unique role among the neutrophil CEACAMs. A model in which CEACAMs dimerize to form signaling complexes could accommodate the observations. Similar interactions may occur in other cells expressing CEACAMs.",2008 Dec 10,"['Skubitz, Keith M', 'Skubitz, Amy PN']",J Transl Med,,,True
7234aab6f4e46d4349fee1e8b38412a5eaebbe3f,PMC,Rift Valley Fever Virus NSs Protein Promotes Post-Transcriptional Downregulation of Protein Kinase PKR and Inhibits eIF2α Phosphorylation,http://dx.doi.org/10.1371/journal.ppat.1000287,PMC2629125,19197350,CC BY,"Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock. A nonstructural RVFV NSs protein inhibits the transcription of host mRNAs, including interferon-β mRNA, and is a major virulence factor. The present study explored a novel function of the RVFV NSs protein by testing the replication of RVFV lacking the NSs gene in the presence of actinomycin D (ActD) or α-amanitin, both of which served as a surrogate of the host mRNA synthesis suppression function of the NSs. In the presence of the host-transcriptional inhibitors, the replication of RVFV lacking the NSs protein, but not that carrying NSs, induced double-stranded RNA-dependent protein kinase (PKR)–mediated eukaryotic initiation factor (eIF)2α phosphorylation, leading to the suppression of host and viral protein translation. RVFV NSs promoted post-transcriptional downregulation of PKR early in the course of the infection and suppressed the phosphorylated eIF2α accumulation. These data suggested that a combination of RVFV replication and NSs-induced host transcriptional suppression induces PKR-mediated eIF2α phosphorylation, while the NSs facilitates efficient viral translation by downregulating PKR and inhibiting PKR-mediated eIF2α phosphorylation. Thus, the two distinct functions of the NSs, i.e., the suppression of host transcription, including that of type I interferon mRNAs, and the downregulation of PKR, work together to prevent host innate antiviral functions, allowing efficient replication and survival of RVFV in infected mammalian hosts.",2009 Feb 6,"['Ikegami, Tetsuro', 'Narayanan, Krishna', 'Won, Sungyong', 'Kamitani, Wataru', 'Peters, C. J.', 'Makino, Shinji']",PLoS Pathog,,,True
f997749a5fc2672a931ecc329c5f3e1c4c6cae9b,PMC,Bear bile: dilemma of traditional medicinal use and animal protection,http://dx.doi.org/10.1186/1746-4269-5-2,PMC2630947,19138420,CC BY,"Bear bile has been used in Traditional Chinese Medicine (TCM) for thousands of years. Modern investigations showed that it has a wide range of pharmacological actions with little toxicological side effect and the pure compounds have been used for curing hepatic and biliary disorders for decades. However, extensive consumption of bear bile made bears endangered species. In the 1980's, bear farming was established in China to extract bear bile from living bears with ""Free-dripping Fistula Technique"". Bear farming is extremely inhumane and many bears died of illness such as chronic infections and liver cancer. Efforts are now given by non-governmental organizations, mass media and Chinese government to end bear farming ultimately. At the same time, systematic research has to be done to find an alternative for bear bile. In this review, we focused on the literature, laboratory and clinical results related to bear bile and its substitutes or alternative in English and Chinese databases. We examined the substitutes or alternative of bear bile from three aspects: pure compounds derived from bear bile, biles from other animals and herbs from TCM. We then discussed the strategy for stopping the trading of bear bile and issues of bear bile related to potential alternative candidates, existing problems in alternative research and work to be done in the future.",2009 Jan 12,"['Feng, Yibin', 'Siu, Kayu', 'Wang, Ning', 'Ng, Kwan-Ming', 'Tsao, Sai-Wah', 'Nagamatsu, Tadashi', 'Tong, Yao']",J Ethnobiol Ethnomed,,,True
90662d7dc7b09e018829ae2bc13e167b218931d8,PMC,Generation of potent neutralizing human monoclonal antibodies against cytomegalovirus infection from immune B cells,http://dx.doi.org/10.1186/1472-6750-8-85,PMC2631500,19014469,CC BY,"BACKGROUND: Human monoclonal antibodies (mAbs) generated as a result of the immune response are likely to be the most effective therapeutic antibodies, particularly in the case of infectious diseases against which the immune response is protective. Human cytomegalovirus (HCMV) is an ubiquitous opportunistic virus that is the most serious pathogenic agent in transplant patients. The available therapeutic armamentarium (e.g. HCMV hyperimmune globulins or antivirals) is associated with severe side effects and the emergence of drug-resistant strains; therefore, neutralizing human mAb may be a decisive alternative in the prevention of primary and re-activated HCMV infections in these patients. RESULTS: The purpose of this study was to generate neutralizing mAb against HCMV from the immunological repertoire of immune donors. To this aim, we designed an efficient technology relying on two discrete and sequential steps: first, human B-lymphocytes are stimulated with TLR9-agonists and IL-2; second, after both additives are removed, the cells are infected with EBV. Using this strategy we obtained 29 clones secreting IgG neutralizing the HCMV infectivity; four among these were further characterized. All of the mAbs neutralize the infection in different combinations of HCMV strains and target cells, with a potency ~20 fold higher than that of the HCMV hyperimmune globulins, currently used in transplant recipients. Recombinant human monoclonal IgG1 suitable as a prophylactic or therapeutic tool in clinical applications has been generated. CONCLUSION: The technology described has proven to be more reproducible, efficient and rapid than previously reported techniques, and can be adopted at low overall costs by any cell biology laboratory for the development of fully human mAbs for immunotherapeutic uses.",2008 Nov 12,"['Funaro, Ada', 'Gribaudo, Giorgio', 'Luganini, Anna', 'Ortolan, Erika', 'Lo Buono, Nicola', 'Vicenzi, Elisa', 'Cassetta, Luca', 'Landolfo, Santo', 'Buick, Richard', 'Falciola, Luca', 'Murphy, Marianne', 'Garotta, Gianni', 'Malavasi, Fabio']",BMC Biotechnol,,,True
eb824213356f63dbaabe4c3f454914e24d6e6a71,PMC,DDESC: Dragon database for exploration of sodium channels in human,http://dx.doi.org/10.1186/1471-2164-9-622,PMC2631582,19099596,CC BY,"BACKGROUND: Sodium channels are heteromultimeric, integral membrane proteins that belong to a superfamily of ion channels. The mutations in genes encoding for sodium channel proteins have been linked with several inherited genetic disorders such as febrile epilepsy, Brugada syndrome, ventricular fibrillation, long QT syndrome, or channelopathy associated insensitivity to pain. In spite of these significant effects that sodium channel proteins/genes could have on human health, there is no publicly available resource focused on sodium channels that would support exploration of the sodium channel related information. RESULTS: We report here Dragon Database for Exploration of Sodium Channels in Human (DDESC), which provides comprehensive information related to sodium channels regarding different entities, such as ""genes and proteins"", ""metabolites and enzymes"", ""toxins"", ""chemicals with pharmacological effects"", ""disease concepts"", ""human anatomy"", ""pathways and pathway reactions"" and their potential links. DDESC is compiled based on text- and data-mining. It allows users to explore potential associations between different entities related to sodium channels in human, as well as to automatically generate novel hypotheses. CONCLUSION: DDESC is first publicly available resource where the information related to sodium channels in human can be explored at different levels. This database is freely accessible for academic and non-profit users via the worldwide web .",2008 Dec 20,"['Sagar, Sunil', 'Kaur, Mandeep', 'Dawe, Adam', 'Seshadri, Sundararajan Vijayaraghava', 'Christoffels, Alan', 'Schaefer, Ulf', 'Radovanovic, Aleksandar', 'Bajic, Vladimir B']",BMC Genomics,,,True
ad7c54f9cbd1779ce878360e15699bebcbd80cd6,PMC,Molecular characterisation of a bovine-like rotavirus detected from a giraffe,http://dx.doi.org/10.1186/1746-6148-4-46,PMC2632637,19014526,CC BY,"BACKGROUND: Rotavirus (RV), is a member of the Reoviridae family and an important etiological agent of acute viral gastroenteritis in the young. Rotaviruses have a wide host range infecting a broad range of animal species, however little is known about rotavirus infection in exotic animals. In this paper we report the first characterisation of a RV strain from a giraffe calf. RESULTS: This report describes the identification and detailed molecular characterisation of a rotavirus strain detected from a 14-day-old Giraffe (Giraffa camelopardalis), presenting with acute diarrhea. The RV strain detected from the giraffe was characterized molecularly as G10P[11]. Detailed sequence analysis of VP4 and VP7 revealed significant identity at the amino acid sequence level to Bovine RV (BoRV). CONCLUSION: This study demonstrates the need for continuous surveillance of RV strains in various animal populations, which will facilitate the identification of rotavirus hosts not previously reported. Furthermore, extending typical epidemiology studies to a broader host range will contribute to the timely identification of new emerging strain types.",2008 Nov 13,"['Mulherin, Emily', 'Bryan, Jill', 'Beltman, Marijke', ""O'Grady, Luke"", 'Pidgeon, Eugene', 'Garon, Lucie', 'Lloyd, Andrew', 'Bainbridge, John', ""O'Shea, Helen"", 'Whyte, Paul', 'Fanning, Séamus']",BMC Vet Res,,,True
27bafe2069fadba9638ec9eb5ae1afaf3c78cfb8,PMC,Mechanisms of HIV non-progression; robust and sustained CD4+ T-cell proliferative responses to p24 antigen correlate with control of viraemia and lack of disease progression after long-term transfusion-acquired HIV-1 infection,http://dx.doi.org/10.1186/1742-4690-5-112,PMC2633348,19077215,CC BY,"BACKGROUND: Elite non-progressors (plasma viral load <50 copies/ml while antiretroviral naive) constitute a tiny fraction of HIV-infected individuals. After 12 years follow-up of a cohort of 13 long-term non-progressors (LTNP) identified from 135 individuals with transfusion-acquired HIV infection, 5 remained LTNP after 23 to 26 years infection, but only 3 retained elite LTNP status. We examined the mechanisms that differentiated delayed progressors from LTNP in this cohort. RESULTS: A survival advantage was conferred on 12 of 13 subjects, who had at least one host genetic factor (HLA, chemokine receptor or TLR polymorphisms) or viral attenuating factor (defective nef) associated with slow progression. However, antiviral immune responses differentiated the course of disease into and beyond the second decade of infection. A stable p24-specific proliferative response was associated with control of viraemia and retention of non-progressor status, but this p24 response was absent or declined in viraemic subjects. Strong Gag-dominant cytotoxic T lymphocyte (CTL) responses were identified in most LTNP, or Pol dominant-CTL in those with nef-defective HIV infection. CTL were associated with control of viraemia when combined with p24 proliferative responses. However, CTL did not prevent late disease progression. Individuals with sustained viral suppression had CTL recognising numerous Gag epitopes, while strong but restricted responses to one or two immunodominant epitopes was effective for some time, but failed to contain viraemia over the course of this study. Viral escape mutants at a HLA B27-restricted Gag-p24 epitope were detected in only 1 of 3 individuals, whereas declining or negative p24 proliferative responses occurred in all 3 concurrent with an increase in viraemia. CONCLUSION: Detectable viraemia at study entry was predictive of loss of LTNP status and/or disease progression in 6 of 8, and differentiated slow progressors from elite LTNP who retained potent virological control. Sustained immunological suppression of viraemia was independently associated with preserved p24 proliferative responses, regardless of the strength and breadth of the CTL response. A decline in this protective p24 response preceded or correlated with loss of non-progressor status and/or signs of disease progression.",2008 Dec 11,"['Dyer, Wayne B', 'Zaunders, John J', 'Yuan, Fang Fang', 'Wang, Bin', 'Learmont, Jennifer C', 'Geczy, Andrew F', 'Saksena, Nitin K', 'McPhee, Dale A', 'Gorry, Paul R', 'Sullivan, John S']",Retrovirology,,,True
1f3077db9137fe7b7cc858899628f1625cbf0644,PMC,Survey of Slaughtered Pigs for Occurrence of Ochratoxin A and Porcine Nephropathy in Serbia,http://dx.doi.org/10.3390/ijms9112169,PMC2635621,19330066,CC BY,"Samples of blood, kidney and liver were randomly selected from slaughtered pigs (n=90) and analyzed for ochratoxin A by HPLC. In addition, in order to obtain information on the occurrence of nephropathy, histological examinations were carried out. Of the 90 liver samples, 26.6% contained OTA in the range of 0.22–14.5 ng/g. The incidence of OTA in serum and kidney were very similar (31%, 33.3%), with a maximum concentration of 220.8 ng/mL, and 52.5 ng/g, respectively. Histopathological examination of kidneys confirmed tubulopathies with edema and cell vacuolization. In addition, hemorrhages and necrosis of proximal kidney tubules’ cells were found.",2008 Nov 7,"['Milićević, Dragan', 'Jurić, Verica', 'Stefanović, Srđan', 'Jovanović, Milijan', 'Janković, Saša']",Int J Mol Sci,,,True
910a5b6256028ed6f3d360a28f14f49488b56db4,PMC,Recent Developments in Peptide-Based Nucleic Acid Delivery,http://dx.doi.org/10.3390/ijms9071276,PMC2635728,19325804,CC BY,"Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cell-penetrating peptides (CPPs). The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10–30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisense-oligonucleotides), which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls.",2008 Jul 16,"['Veldhoen, Sandra', 'Laufer, Sandra D.', 'Restle, Tobias']",Int J Mol Sci,,,True
fd955af6faa247ced61613abf842cf3affac6bb2,PMC,Broad-Spectrum Drugs Against Viral Agents,http://dx.doi.org/10.3390/ijms9091561,PMC2635754,19325820,CC BY,"Development of antivirals has focused primarily on vaccines and on treatments for specific viral agents. Although effective, these approaches may be limited in situations where the etiologic agent is unknown or when the target virus has undergone mutation, recombination or reassortment. Augmentation of the innate immune response may be an effective alternative for disease amelioration. Nonspecific, broad-spectrum immune responses can be induced by double-stranded (ds)RNAs such as poly (ICLC), or oligonucleotides (ODNs) containing unmethylated deocycytidyl-deoxyguanosinyl (CpG) motifs. These may offer protection against various bacterial and viral pathogens regardless of their genetic makeup, zoonotic origin or drug resistance.",2008 Sep 1,"['Christopher, Mary E.', 'Wong, Jonathan P.']",Int J Mol Sci,,,True
184c8c4637d343cd81dddd0d3f5e6c922f538afe,PMC,In Very Young Infants Severity of Acute Bronchiolitis Depends On Carried Viruses,http://dx.doi.org/10.1371/journal.pone.0004596,PMC2644758,19240806,CC BY,"BACKGROUND: RT amplification reaction has revealed that various single viruses or viral co-infections caused acute bronchiolitis in infants, and RV appeared to have a growing involvement in early respiratory diseases. Because remaining controversial, the objective was to determine prospectively the respective role of RSV, RV, hMPV and co-infections on the severity of acute bronchiolitis in very young infants. METHODS AND PRINCIPAL FINDINGS: 209 infants (median age: 2.4 months) were enrolled in a prospective study of infants <1 year old, hospitalized for a first episode of bronchiolitis during the winter epidemic season and with no high risk for severe disease. The severity was assessed by recording SaO(2)% at admission, a daily clinical score (scale 0–18), the duration of oxygen supplementation and the length of hospitalization. Viruses were identified in 94.7% by RT amplification reaction: RSV only (45.8%), RV only (7.2%), hMPV only (3.8%), dual RSV/RV (14.3%), and other virus only (2%) or coinfections (9%). RV compared respectively with RSV and dual RSV/RV infection caused a significant less severe disease with a lower clinical score (5[3.2–6] vs. 6[4–8], p = 0.01 and 5.5[5–7], p = 0.04), a shorter time in oxygen supplementation (0[0–1] days vs. 2[0–3] days, p = 0.02 and 2[0–3] days, p = 0.03) and a shorter hospital stay (3[3–4.7] days vs.6 [5–8] days, p = 0.001 and 5[4–6] days, p = 0.04). Conversely, RSV infants had also longer duration of hospitalization in comparison with RSV/RV (p = 0.01) and hMPV (p = 0.04). The multivariate analyses showed that the type of virus carried was independently associated with the duration of hospitalization. CONCLUSION: This study underlined the role of RV in early respiratory diseases, as frequently carried by young infants with a first acute bronchiolitis. RSV caused the more severe disease and conversely RV the lesser severity. No additional effect of dual RSV/RV infection was observed on the severity.",2009 Feb 25,"['Marguet, Christophe', 'Lubrano, Marc', 'Gueudin, Marie', 'Le Roux, Pascal', 'Deschildre, Antoine', 'Forget, Chantal', 'Couderc, Laure', 'Siret, Daniel', 'Donnou, Marie-Dominique', 'Bubenheim, Michael', 'Vabret, Astrid', 'Freymuth, François']",PLoS One,,,True
f3de553d9173bab4ad066e7d00994c165a7d9a41,PMC,The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action,http://dx.doi.org/10.2174/138920207783591690,PMC2647156,19412418,CC BY,"The HLA region encodes several molecules that play key roles in the immune system. Strong association between the HLA region and autoimmune disease (AID) has been established for over fifty years. Association of components of the HLA class II encoded HLA-DRB1-DQA1-DQB1 haplotype has been detected with several AIDs, including rheumatoid arthritis, type 1 diabetes and Graves’ disease. Molecules encoded by this region play a key role in exogenous antigen presentation to CD4+ Th cells, indicating the importance of this pathway in AID initiation and progression. Although other components of the HLA class I and III regions have also been investigated for association with AID, apart from the association of HLA-B*27 with ankylosing spondylitis, it has been difficult to determine additional susceptibility loci independent of the strong linkage disequilibrium (LD) with the HLA class II genes. Recent advances in the statistical analysis of LD and the recruitment of large AID datasets have allowed investigation of the HLA class I and III regions to be re-visited. Association of the HLA class I region, independent of known HLA class II effects, has now been detected for several AIDs, including strong association of HLA-B with type 1 diabetes and HLA-C with multiple sclerosis and Graves’ disease. These results provide further evidence of a possible role for bacterial or viral infection and CD8+ T cells in AID onset. The advances being made in determining the primary associations within the HLA region and AIDs will not only increase our understanding of the mechanisms behind disease pathogenesis but may also aid in the development of novel therapeutic targets in the future.",2007 Nov,"['Gough, S.C.L', 'Simmonds, M.J']",Curr Genomics,,,True
7af827f235679f6d05974e8e5c5ca434642eeda2,PMC,A Discontinuous RNA Platform Mediates RNA Virus Replication: Building an Integrated Model for RNA–based Regulation of Viral Processes,http://dx.doi.org/10.1371/journal.ppat.1000323,PMC2648310,19266082,CC BY,"Plus-strand RNA viruses contain RNA elements within their genomes that mediate a variety of fundamental viral processes. The traditional view of these elements is that of local RNA structures. This perspective, however, is changing due to increasing discoveries of functional viral RNA elements that are formed by long-range RNA–RNA interactions, often spanning thousands of nucleotides. The plus-strand RNA genomes of tombusviruses exemplify this concept by possessing different long-range RNA–RNA interactions that regulate both viral translation and transcription. Here we report that a third fundamental tombusvirus process, viral genome replication, requires a long-range RNA–based interaction spanning ∼3000 nts. In vivo and in vitro analyses suggest that the discontinuous RNA platform formed by the interaction facilitates efficient assembly of the viral RNA replicase. This finding has allowed us to build an integrated model for the role of global RNA structure in regulating the reproduction of a eukaryotic RNA virus, and the insights gained have extended our understanding of the multifunctional nature of viral RNA genomes.",2009 Mar 6,"['Wu, Baodong', 'Pogany, Judit', 'Na, Hong', 'Nicholson, Beth L.', 'Nagy, Peter D.', 'White, K. Andrew']",PLoS Pathog,,,True
e5e8b3747bbc731a8ef8ceab73882ec5cff818ef,PMC,A Discontinuous RNA Platform Mediates RNA Virus Replication: Building an Integrated Model for RNA–based Regulation of Viral Processes,http://dx.doi.org/10.1371/journal.ppat.1000323,PMC2648310,19266082,CC BY,"Plus-strand RNA viruses contain RNA elements within their genomes that mediate a variety of fundamental viral processes. The traditional view of these elements is that of local RNA structures. This perspective, however, is changing due to increasing discoveries of functional viral RNA elements that are formed by long-range RNA–RNA interactions, often spanning thousands of nucleotides. The plus-strand RNA genomes of tombusviruses exemplify this concept by possessing different long-range RNA–RNA interactions that regulate both viral translation and transcription. Here we report that a third fundamental tombusvirus process, viral genome replication, requires a long-range RNA–based interaction spanning ∼3000 nts. In vivo and in vitro analyses suggest that the discontinuous RNA platform formed by the interaction facilitates efficient assembly of the viral RNA replicase. This finding has allowed us to build an integrated model for the role of global RNA structure in regulating the reproduction of a eukaryotic RNA virus, and the insights gained have extended our understanding of the multifunctional nature of viral RNA genomes.",2009 Mar 6,"['Wu, Baodong', 'Pogany, Judit', 'Na, Hong', 'Nicholson, Beth L.', 'Nagy, Peter D.', 'White, K. Andrew']",PLoS Pathog,,,False
ec84301b786a7e9bb2745f5a4141a69e484a92f3,PMC,Smallpox and Season: Reanalysis of Historical Data,http://dx.doi.org/10.1155/2009/591935,PMC2648660,19266090,CC BY,"Seasonal variation in smallpox transmission is one of the most pressing ecological questions and is relevant to bioterrorism preparedness. The present study reanalyzed 7 historical datasets which recorded monthly cases or deaths. In addition to time series analyses of reported data, an estimation and spectral analysis of the effective reproduction number at calendar time t, R(t), were made. Meteorological variables were extracted from a report in India from 1890–1921 and compared with smallpox mortality as well as R(t). Annual cycles of smallpox transmission were clearly shown not only in monthly reports but also in the estimates of R(t). Even short-term epidemic data clearly exhibited an annual peak every January. Both mortality and R(t) revealed significant negative association (P < .01) and correlation (P < .01), respectively, with humidity. These findings suggest that smallpox transmission greatly varies with season and is most likely enhanced by dry weather.",2009 Jan 4,"['Nishiura, Hiroshi', 'Kashiwagi, Tomoko']",Interdiscip Perspect Infect Dis,,,True
741b4227809cd635e7f0f06cf4f70331a9764b5f,PMC,A computational analysis of SARS cysteine proteinase-octapeptide substrate interaction: implication for structure and active site binding mechanism,http://dx.doi.org/10.1186/1471-2105-10-S1-S48,PMC2648740,19208150,CC BY,"BACKGROUND: SARS coronavirus main proteinase (SARS CoVMpro) is an important enzyme for the replication of Severe Acute Respiratory Syndrome virus. The active site region of SARS CoVMpro is divided into 8 subsites. Understanding the binding mode of SARS CoVMpro with a specific substrate is useful and contributes to structural-based drug design. The purpose of this research is to investigate the binding mode between the SARS CoVMpro and two octapeptides, especially in the region of the S3 subsite, through a molecular docking and molecular dynamics (MD) simulation approach. RESULTS: The one turn α-helix chain (residues 47–54) of the SARS CoVMpro was directly involved in the induced-fit model of the enzyme-substrate complex. The S3 subsite of the enzyme had a negatively charged region due to the presence of Glu47. During MD simulations, Glu47 of the enzyme was shown to play a key role in electrostatic bonding with the P3Lys of the octapeptide. CONCLUSION: MD simulations were carried out on the SARS CoVMpro-octapeptide complex. The hypothesis proposed that Glu47 of SARS CoVMpro is an important residue in the S3 subsite and is involved in binding with P3Lys of the octapeptide.",2009 Jan 30,"['Phakthanakanok, Krongsakda', 'Ratanakhanokchai, Khanok', 'Kyu, Khin Lay', 'Sompornpisut, Pornthep', 'Watts, Aaron', 'Pinitglang, Surapong']",BMC Bioinformatics,,,True
084df43c5fc9b52ac507f090c6d892b69e5b0999,PMC,Feline Leukemia Virus and Other Pathogens as Important Threats to the Survival of the Critically Endangered Iberian Lynx (Lynx pardinus),http://dx.doi.org/10.1371/journal.pone.0004744,PMC2649436,19270739,CC BY,"BACKGROUND: The Iberian lynx (Lynx pardinus) is considered the most endangered felid species in the world. In order to save this species, the Spanish authorities implemented a captive breeding program recruiting lynxes from the wild. In this context, a retrospective survey on prevalence of selected feline pathogens in free-ranging lynxes was initiated. METHODOLOGY/ PRINCIPAL FINDINGS: We systematically analyzed the prevalence and importance of seven viral, one protozoan (Cytauxzoon felis), and several bacterial (e.g., hemotropic mycoplasma) infections in 77 of approximately 200 remaining free-ranging Iberian lynxes of the Doñana and Sierra Morena areas, in Southern Spain, between 2003 and 2007. With the exception of feline immunodeficiency virus (FIV), evidence of infection by all tested feline pathogens was found in Iberian lynxes. Fourteen lynxes were feline leukemia virus (FeLV) provirus-positive; eleven of these were antigenemic (FeLV p27 positive). All 14 animals tested negative for other viral infections. During a six-month period in 2007, six of the provirus-positive antigenemic lynxes died. Infection with FeLV but not with other infectious agents was associated with mortality (p<0.001). Sequencing of the FeLV surface glycoprotein gene revealed a common origin for ten of the eleven samples. The ten sequences were closely related to FeLV-A/61E, originally isolated from cats in the USA. Endogenous FeLV sequences were not detected. CONCLUSIONS/SIGNIFICANCE: It was concluded that the FeLV infection most likely originated from domestic cats invading the lynx's habitats. Data available regarding the time frame, co-infections, and outcome of FeLV-infections suggest that, in contrast to the domestic cat, the FeLV strain affecting the lynxes in 2007 is highly virulent to this species. Our data argue strongly for vaccination of lynxes and domestic cats in and around lynx's habitats in order to prevent further spread of the virus as well as reduction the domestic cat population if the lynx population is to be maintained.",2009 Mar 9,"['Meli, Marina L.', 'Cattori, Valentino', 'Martínez, Fernando', 'López, Guillermo', 'Vargas, Astrid', 'Simón, Miguel A.', 'Zorrilla, Irene', 'Muñoz, Alvaro', 'Palomares, Francisco', 'López-Bao, Jose V.', 'Pastor, Josep', 'Tandon, Ravi', 'Willi, Barbara', 'Hofmann-Lehmann, Regina', 'Lutz, Hans']",PLoS One,,,True
c3f83fef0e35a95a6ff12ffacf58969db6172761,PMC,Ciliary Beating Recovery in Deficient Human Airway Epithelial Cells after Lentivirus Ex Vivo Gene Therapy,http://dx.doi.org/10.1371/journal.pgen.1000422,PMC2650261,19300481,CC BY,"Primary Ciliary Dyskinesia is a heterogeneous genetic disease that is characterized by cilia dysfunction of the epithelial cells lining the respiratory tracts, resulting in recurrent respiratory tract infections. Despite lifelong physiological therapy and antibiotics, the lungs of affected patients are progressively destroyed, leading to respiratory insufficiency. Recessive mutations in Dynein Axonemal Intermediate chain type 1 (DNAI1) gene have been described in 10% of cases of Primary Ciliary Dyskinesia. Our goal was to restore normal ciliary beating in DNAI1–deficient human airway epithelial cells. A lentiviral vector based on Simian Immunodeficiency Virus pseudotyped with Vesicular Stomatitis Virus Glycoprotein was used to transduce cultured human airway epithelial cells with a cDNA of DNAI1 driven by the Elongation Factor 1 promoter. Transcription and translation of the transduced gene were tested by RT–PCR and western blot, respectively. Human airway epithelial cells that were DNAI1–deficient due to compound heterozygous mutations, and consequently had immotile cilia and no outer dynein arm, were transduced by the lentivirus. Cilia beating was recorded and electron microscopy of the cilia was performed. Transcription and translation of the transduced DNAI1 gene were detected in human cells treated with the lentivirus. In addition, immotile cilia recovered a normal beat and outer dynein arms reappeared. We demonstrated that it is possible to obtain a normalization of ciliary beat frequency of deficient human airway epithelial cells by using a lentivirus to transduce cells with the therapeutic gene. This preliminary step constitutes a conceptual proof that is indispensable in the perspective of Primary Ciliary Dyskinesia's in vivo gene therapy. This is the first time that recovery of cilia beating is demonstrated in this disease.",2009 Mar 20,"['Chhin, Brigitte', 'Negre, Didier', 'Merrot, Olivier', 'Pham, Jacqueline', 'Tourneur, Yves', 'Ressnikoff, Denis', 'Jaspers, Martine', 'Jorissen, Mark', 'Cosset, François-Loïc', 'Bouvagnet, Patrice']",PLoS Genet,,,True
ce4252922cce80f4284eae7607b1967b35596ef5,PMC,Ciliary Beating Recovery in Deficient Human Airway Epithelial Cells after Lentivirus Ex Vivo Gene Therapy,http://dx.doi.org/10.1371/journal.pgen.1000422,PMC2650261,19300481,CC BY,"Primary Ciliary Dyskinesia is a heterogeneous genetic disease that is characterized by cilia dysfunction of the epithelial cells lining the respiratory tracts, resulting in recurrent respiratory tract infections. Despite lifelong physiological therapy and antibiotics, the lungs of affected patients are progressively destroyed, leading to respiratory insufficiency. Recessive mutations in Dynein Axonemal Intermediate chain type 1 (DNAI1) gene have been described in 10% of cases of Primary Ciliary Dyskinesia. Our goal was to restore normal ciliary beating in DNAI1–deficient human airway epithelial cells. A lentiviral vector based on Simian Immunodeficiency Virus pseudotyped with Vesicular Stomatitis Virus Glycoprotein was used to transduce cultured human airway epithelial cells with a cDNA of DNAI1 driven by the Elongation Factor 1 promoter. Transcription and translation of the transduced gene were tested by RT–PCR and western blot, respectively. Human airway epithelial cells that were DNAI1–deficient due to compound heterozygous mutations, and consequently had immotile cilia and no outer dynein arm, were transduced by the lentivirus. Cilia beating was recorded and electron microscopy of the cilia was performed. Transcription and translation of the transduced DNAI1 gene were detected in human cells treated with the lentivirus. In addition, immotile cilia recovered a normal beat and outer dynein arms reappeared. We demonstrated that it is possible to obtain a normalization of ciliary beat frequency of deficient human airway epithelial cells by using a lentivirus to transduce cells with the therapeutic gene. This preliminary step constitutes a conceptual proof that is indispensable in the perspective of Primary Ciliary Dyskinesia's in vivo gene therapy. This is the first time that recovery of cilia beating is demonstrated in this disease.",2009 Mar 20,"['Chhin, Brigitte', 'Negre, Didier', 'Merrot, Olivier', 'Pham, Jacqueline', 'Tourneur, Yves', 'Ressnikoff, Denis', 'Jaspers, Martine', 'Jorissen, Mark', 'Cosset, François-Loïc', 'Bouvagnet, Patrice']",PLoS Genet,,,True
a5e0a0ed5bd96d5d8bda79b3b77b68ade21eaee0,PMC,Novel concepts in virally induced asthma,http://dx.doi.org/10.1186/1476-7961-7-2,PMC2651109,19154602,CC BY,"Viruses are the predominant infectious cause of asthma exacerbations in the developed world. In addition, recent evidence strongly suggests that viral infections may also have a causal role in the development of childhood asthma. In this article, we will briefly describe the general perception of how the link between infections and asthma has changed over the last century, and then focus on very recent developments that have provided new insights into the contribution of viruses to asthma pathogenesis. Highlighted areas include the contribution of severe early life viral infections to asthma inception, genetic determinants of severe viral infections in infancy, the differences in innate and adaptive immune system cytokine responses to viral infection between asthmatic and nonasthmatic subjects, and a potential vaccine strategy to prevent severe early life virally-induced illness.",2009 Jan 20,"['Huckabee, Matthew M', 'Peebles, R Stokes']",Clin Mol Allergy,,,True
31b039f27dbcd96df12be89f281f576d26fe80e1,PMC,The Complete Genome and Proteome of Laribacter hongkongensis Reveal Potential Mechanisms for Adaptations to Different Temperatures and Habitats,http://dx.doi.org/10.1371/journal.pgen.1000416,PMC2652115,19283063,CC BY,"Laribacter hongkongensis is a newly discovered Gram-negative bacillus of the Neisseriaceae family associated with freshwater fish–borne gastroenteritis and traveler's diarrhea. The complete genome sequence of L. hongkongensis HLHK9, recovered from an immunocompetent patient with severe gastroenteritis, consists of a 3,169-kb chromosome with G+C content of 62.35%. Genome analysis reveals different mechanisms potentially important for its adaptation to diverse habitats of human and freshwater fish intestines and freshwater environments. The gene contents support its phenotypic properties and suggest that amino acids and fatty acids can be used as carbon sources. The extensive variety of transporters, including multidrug efflux and heavy metal transporters as well as genes involved in chemotaxis, may enable L. hongkongensis to survive in different environmental niches. Genes encoding urease, bile salts efflux pump, adhesin, catalase, superoxide dismutase, and other putative virulence factors—such as hemolysins, RTX toxins, patatin-like proteins, phospholipase A1, and collagenases—are present. Proteomes of L. hongkongensis HLHK9 cultured at 37°C (human body temperature) and 20°C (freshwater habitat temperature) showed differential gene expression, including two homologous copies of argB, argB-20, and argB-37, which encode two isoenzymes of N-acetyl-L-glutamate kinase (NAGK)—NAGK-20 and NAGK-37—in the arginine biosynthesis pathway. NAGK-20 showed higher expression at 20°C, whereas NAGK-37 showed higher expression at 37°C. NAGK-20 also had a lower optimal temperature for enzymatic activities and was inhibited by arginine probably as negative-feedback control. Similar duplicated copies of argB are also observed in bacteria from hot springs such as Thermus thermophilus, Deinococcus geothermalis, Deinococcus radiodurans, and Roseiflexus castenholzii, suggesting that similar mechanisms for temperature adaptation may be employed by other bacteria. Genome and proteome analysis of L. hongkongensis revealed novel mechanisms for adaptations to survival at different temperatures and habitats.",2009 Mar 13,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Tse, Herman', 'Teng, Jade L. L.', 'Curreem, Shirly O. T.', 'Tsang, Alan K. L.', 'Fan, Rachel Y. Y.', 'Wong, Gilman K. M.', 'Huang, Yi', 'Loman, Nicholas J.', 'Snyder, Lori A. S.', 'Cai, James J.', 'Huang, Jian-Dong', 'Mak, William', 'Pallen, Mark J.', 'Lok, Si', 'Yuen, Kwok-Yung']",PLoS Genet,,,True
3dd8a16b73bc8a692aa50ed576665adfe598db84,PMC,The Complete Genome and Proteome of Laribacter hongkongensis Reveal Potential Mechanisms for Adaptations to Different Temperatures and Habitats,http://dx.doi.org/10.1371/journal.pgen.1000416,PMC2652115,19283063,CC BY,"Laribacter hongkongensis is a newly discovered Gram-negative bacillus of the Neisseriaceae family associated with freshwater fish–borne gastroenteritis and traveler's diarrhea. The complete genome sequence of L. hongkongensis HLHK9, recovered from an immunocompetent patient with severe gastroenteritis, consists of a 3,169-kb chromosome with G+C content of 62.35%. Genome analysis reveals different mechanisms potentially important for its adaptation to diverse habitats of human and freshwater fish intestines and freshwater environments. The gene contents support its phenotypic properties and suggest that amino acids and fatty acids can be used as carbon sources. The extensive variety of transporters, including multidrug efflux and heavy metal transporters as well as genes involved in chemotaxis, may enable L. hongkongensis to survive in different environmental niches. Genes encoding urease, bile salts efflux pump, adhesin, catalase, superoxide dismutase, and other putative virulence factors—such as hemolysins, RTX toxins, patatin-like proteins, phospholipase A1, and collagenases—are present. Proteomes of L. hongkongensis HLHK9 cultured at 37°C (human body temperature) and 20°C (freshwater habitat temperature) showed differential gene expression, including two homologous copies of argB, argB-20, and argB-37, which encode two isoenzymes of N-acetyl-L-glutamate kinase (NAGK)—NAGK-20 and NAGK-37—in the arginine biosynthesis pathway. NAGK-20 showed higher expression at 20°C, whereas NAGK-37 showed higher expression at 37°C. NAGK-20 also had a lower optimal temperature for enzymatic activities and was inhibited by arginine probably as negative-feedback control. Similar duplicated copies of argB are also observed in bacteria from hot springs such as Thermus thermophilus, Deinococcus geothermalis, Deinococcus radiodurans, and Roseiflexus castenholzii, suggesting that similar mechanisms for temperature adaptation may be employed by other bacteria. Genome and proteome analysis of L. hongkongensis revealed novel mechanisms for adaptations to survival at different temperatures and habitats.",2009 Mar 13,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Tse, Herman', 'Teng, Jade L. L.', 'Curreem, Shirly O. T.', 'Tsang, Alan K. L.', 'Fan, Rachel Y. Y.', 'Wong, Gilman K. M.', 'Huang, Yi', 'Loman, Nicholas J.', 'Snyder, Lori A. S.', 'Cai, James J.', 'Huang, Jian-Dong', 'Mak, William', 'Pallen, Mark J.', 'Lok, Si', 'Yuen, Kwok-Yung']",PLoS Genet,,,False
b710adc78b56eb091aa40bc4cf5bc015e3f567e4,PMC,Genetic Drift of HIV Populations in Culture,http://dx.doi.org/10.1371/journal.pgen.1000431,PMC2652835,19300501,CC BY,"Populations of Human Immunodeficiency Virus type 1 (HIV-1) undergo a surprisingly large amount of genetic drift in infected patients despite very large population sizes, which are predicted to be mostly deterministic. Several models have been proposed to explain this phenomenon, but all of them implicitly assume that the process of virus replication itself does not contribute to genetic drift. We developed an assay to measure the amount of genetic drift for HIV populations replicating in cell culture. The assay relies on creation of HIV populations of known size and measurements of variation in frequency of a neutral allele. Using this assay, we show that HIV undergoes approximately ten times more genetic drift than would be expected from its population size, which we defined as the number of infected cells in the culture. We showed that a large portion of the increase in genetic drift is due to non-synchronous infection of target cells. When infections are synchronized, genetic drift for the virus is only 3-fold higher than expected from its population size. Thus, the stochastic nature of biological processes involved in viral replication contributes to increased genetic drift in HIV populations. We propose that appreciation of these effects will allow better understanding of the evolutionary forces acting on HIV in infected patients.",2009 Mar 20,"['Voronin, Yegor', 'Holte, Sarah', 'Overbaugh, Julie', 'Emerman, Michael']",PLoS Genet,,,True
319da4b3a356bea3794d401087176bcd055ba23d,PMC,Transmission Dynamics and Prospects for the Elimination of Canine Rabies,http://dx.doi.org/10.1371/journal.pbio.1000053,PMC2653555,19278295,CC BY,"Rabies has been eliminated from domestic dog populations in Western Europe and North America, but continues to kill many thousands of people throughout Africa and Asia every year. A quantitative understanding of transmission dynamics in domestic dog populations provides critical information to assess whether global elimination of canine rabies is possible. We report extensive observations of individual rabid animals in Tanzania and generate a uniquely detailed analysis of transmission biology, which explains important epidemiological features, including the level of variation in epidemic trajectories. We found that the basic reproductive number for rabies, R(0), is very low in our study area in rural Africa (∼1.2) and throughout its historic global range (<2). This finding provides strong support for the feasibility of controlling endemic canine rabies by vaccination, even near wildlife areas with large wild carnivore populations. However, we show that rapid turnover of domestic dog populations has been a major obstacle to successful control in developing countries, thus regular pulse vaccinations will be required to maintain population-level immunity between campaigns. Nonetheless our analyses suggest that with sustained, international commitment, global elimination of rabies from domestic dog populations, the most dangerous vector to humans, is a realistic goal.",2009 Mar 10,"['Hampson, Katie', 'Dushoff, Jonathan', 'Cleaveland, Sarah', 'Haydon, Daniel T', 'Kaare, Magai', 'Packer, Craig', 'Dobson, Andy']",PLoS Biol,,,True
7379b8c28321b7f9c78d2b4d35109a87b35cf883,PMC,Interaction of the Coronavirus Infectious Bronchitis Virus Membrane Protein with β-Actin and Its Implication in Virion Assembly and Budding,http://dx.doi.org/10.1371/journal.pone.0004908,PMC2653722,19287488,CC BY,"Coronavirus M protein is an essential component of virion and plays pivotal roles in virion assembly, budding and maturation. The M protein is integrated into the viral envelope with three transmembrane domains flanked by a short amino-terminal ectodomain and a large carboxy-terminal endodomain. In this study, we showed co-purification of the M protein from coronavirus infectious bronchitis virus (IBV) with actin. To understand the cellular factors that may be involved in virion assembly, budding and maturation processes, IBV M was used as the bait in a yeast two-hybrid screen, resulting in the identification of β-actin as a potentially interacting partner. This interaction was subsequently confirmed by coimmunoprecipitation and immunofluorescence microscopy in mammalian cells, and mutation of amino acids A159 and K160 on the M protein abolished the interaction. Introduction of the A159-K160 mutation into an infectious IBV clone system blocks the infectivity of the clone, although viral RNA replication and subgenomic mRNA transcription were actively detected. Disruption of actin filaments with cell-permeable agent cytochalasin D at early stages of the infection cycle led to the detection of viral protein synthesis in infected cells but not release of virus particles to the cultured media. However, the same treatment at late stages of the infection cycle did not affect the release of virus particles to the media, suggesting that disruption of the actin filaments might block virion assembly and budding, but not release of the virus particles. This study reveals an essential function of actin in the replication cycle of coronavirus.",2009 Mar 16,"['Wang, Jibin', 'Fang, Shouguo', 'Xiao, Han', 'Chen, Bo', 'Tam, James P.', 'Liu, Ding Xiang']",PLoS One,,,True
c337fa83ebb25e4600c0f9333ee0cb0fa938e947,PMC,Healthcare workers' attitudes to working during pandemic influenza: a qualitative study,http://dx.doi.org/10.1186/1471-2458-9-56,PMC2654560,19216738,CC BY,"BACKGROUND: Healthcare workers (HCWs) will play a key role in any response to pandemic influenza, and the UK healthcare system's ability to cope during an influenza pandemic will depend, to a large extent, on the number of HCWs who are able and willing to work through the crisis. UK emergency planning will be improved if planners have a better understanding of the reasons UK HCWs may have for their absenteeism, and what might motivate them to work during an influenza pandemic. This paper reports the results of a qualitative study that explored UK HCWs' views (n = 64) about working during an influenza pandemic, in order to identify factors that might influence their willingness and ability to work and to identify potential sources of any perceived duty on HCWs to work. METHODS: A qualitative study, using focus groups (n = 9) and interviews (n = 5). RESULTS: HCWs across a range of roles and grades tended to feel motivated by a sense of obligation to work through an influenza pandemic. A number of significant barriers that may prevent them from doing so were also identified. Perceived barriers to the ability to work included being ill oneself, transport difficulties, and childcare responsibilities. Perceived barriers to the willingness to work included: prioritising the wellbeing of family members; a lack of trust in, and goodwill towards, the NHS; a lack of information about the risks and what is expected of them during the crisis; fear of litigation; and the feeling that employers do not take the needs of staff seriously. Barriers to ability and barriers to willingness, however, are difficult to separate out. CONCLUSION: Although our participants tended to feel a general obligation to work during an influenza pandemic, there are barriers to working, which, if generalisable, may significantly reduce the NHS workforce during a pandemic. The barriers identified are both barriers to willingness and to ability. This suggests that pandemic planning needs to take into account the possibility that staff may be absent for reasons beyond those currently anticipated in UK planning documents. In particular, staff who are physically able to attend work may nonetheless be unwilling to do so. Although there are some barriers that cannot be mitigated by employers (such as illness, transport infrastructure etc.), there are a number of remedial steps that can be taken to lesson the impact of others (providing accommodation, building reciprocity, provision of information and guidance etc). We suggest that barriers to working lie along an ability/willingness continuum, and that absenteeism may be reduced by taking steps to prevent barriers to willingness becoming perceived barriers to ability.",2009 Feb 12,"['Ives, Jonathan', 'Greenfield, Sheila', 'Parry, Jayne M', 'Draper, Heather', 'Gratus, Christine', 'Petts, Judith I', 'Sorell, Tom', 'Wilson, Sue']",BMC Public Health,,,True
ebc8f68d591a7979fcde0afc4cfcae3a9dac58af,PMC,An Amphipathic α-Helix Controls Multiple Roles of Brome Mosaic Virus Protein 1a in RNA Replication Complex Assembly and Function,http://dx.doi.org/10.1371/journal.ppat.1000351,PMC2654722,19325881,CC BY,"Brome mosaic virus (BMV) protein 1a has multiple key roles in viral RNA replication. 1a localizes to perinuclear endoplasmic reticulum (ER) membranes as a peripheral membrane protein, induces ER membrane invaginations in which RNA replication complexes form, and recruits and stabilizes BMV 2a polymerase (2a(Pol)) and RNA replication templates at these sites to establish active replication complexes. During replication, 1a provides RNA capping, NTPase and possibly RNA helicase functions. Here we identify in BMV 1a an amphipathic α-helix, helix A, and use NMR analysis to define its structure and propensity to insert in hydrophobic membrane-mimicking micelles. We show that helix A is essential for efficient 1a–ER membrane association and normal perinuclear ER localization, and that deletion or mutation of helix A abolishes RNA replication. Strikingly, mutations in helix A give rise to two dramatically opposite 1a function phenotypes, implying that helix A acts as a molecular switch regulating the intricate balance between separable 1a functions. One class of helix A deletions and amino acid substitutions markedly inhibits 1a–membrane association and abolishes ER membrane invagination, viral RNA template recruitment, and replication, but doubles the 1a-mediated increase in 2a(Pol) accumulation. The second class of helix A mutations not only maintains efficient 1a–membrane association but also amplifies the number of 1a-induced membrane invaginations 5- to 8-fold and enhances viral RNA template recruitment, while failing to stimulate 2a(Pol) accumulation. The results provide new insights into the pathways of RNA replication complex assembly and show that helix A is critical for assembly and function of the viral RNA replication complex, including its central role in targeting replication components and controlling modes of 1a action.",2009 Mar 27,"['Liu, Ling', 'Westler, William M.', 'den Boon, Johan A.', 'Wang, Xiaofeng', 'Diaz, Arturo', 'Steinberg, H. Adam', 'Ahlquist, Paul']",PLoS Pathog,,,True
0596a285261bc529af5a4bea0447bc838f45866f,PMC,Viruses and thyroiditis: an update,http://dx.doi.org/10.1186/1743-422X-6-5,PMC2654877,19138419,CC BY,"Viral infections are frequently cited as a major environmental factor involved in subacute thyroiditis and autoimmune thyroid diseases This review examines the data related to the role of viruses in the development of thyroiditis. Our research has been focused on human data. We have reviewed virological data for each type of thyroiditis at different levels of evidence; epidemiological data, serological data or research on circulating viruses, direct evidence of thyroid tissue infection. Interpretation of epidemiological and serological data must be cautious as they don't prove that this pathogen is responsible for the disease. However, direct evidence of the presence of viruses or their components in the organ are available for retroviruses (HFV) and mumps in subacute thyroiditis, for retroviruses (HTLV-1, HFV, HIV and SV40) in Graves's disease and for HTLV-1, enterovirus, rubella, mumps virus, HSV, EBV and parvovirus in Hashimoto's thyroiditis. However, it remains to determine whether they are responsible for thyroid diseases or whether they are just innocent bystanders. Further studies are needed to clarify the relationship between viruses and thyroid diseases, in order to develop new strategies for prevention and/or treatment.",2009 Jan 12,"['Desailloud, Rachel', 'Hober, Didier']",Virol J,,,True
3f842ddde61088937e203ddec6ace954e479499e,PMC,Detection of genetically modified organisms (GMOs) using isothermal amplification of target DNA sequences,http://dx.doi.org/10.1186/1472-6750-9-7,PMC2656497,19187544,CC BY,"BACKGROUND: The most common method of GMO detection is based upon the amplification of GMO-specific DNA amplicons using the polymerase chain reaction (PCR). Here we have applied the loop-mediated isothermal amplification (LAMP) method to amplify GMO-related DNA sequences, 'internal' commonly-used motifs for controlling transgene expression and event-specific (plant-transgene) junctions. RESULTS: We have tested the specificity and sensitivity of the technique for use in GMO studies. Results show that detection of 0.01% GMO in equivalent background DNA was possible and dilutions of template suggest that detection from single copies of the template may be possible using LAMP. CONCLUSION: This work shows that GMO detection can be carried out using LAMP for routine screening as well as for specific events detection. Moreover, the sensitivity and ability to amplify targets, even with a high background of DNA, here demonstrated, highlights the advantages of this isothermal amplification when applied for GMO detection.",2009 Feb 2,"['Lee, David', 'La Mura, Maurizio', 'Allnutt, Theo R', 'Powell, Wayne']",BMC Biotechnol,,,True
ee3d6fcf2ed5408aef9c152f2e7145d916a1baee,PMC,Different inflammatory responses are associated with Ureaplasma parvum-induced UTI and urolith formation,http://dx.doi.org/10.1186/1471-2334-9-9,PMC2656517,19171043,CC BY,"BACKGROUND: Epidemiologic studies show a strong association between Ureaplasmas and urogenital tract disease in humans. Since healthy humans can be colonized with Ureaplasmas, its role as a pathogen remains controversial. In order to begin to define the role of the host in disease, we developed a rodent model of urinary tract infection (UTI) using Fischer 344 (F344) rats. Animals were inoculated with sterile broth, 10(1), 10(3), 10(5), 10(7), or 10(9 )log CFU of a rat-adapted strain of Ureaplasma parvum. RESULTS: Infected animals exhibited two distinct profiles, asymptomatic UTI and UTI complicated with struvite urolithiasis. Inoculum dose of U. parvum affected the incidence of UTI, and 50% to 57% of animals inoculated with ≥ 10(7 )CFU of U. parvum remained infected (p < 0.04). However, inoculum dose did not influence immune response to U. parvum. Asymptomatic UTI was characterized by a minimal immune response that was predominantly monocytic and lymphocytic, with limited lesions, and elevated urinary levels of IFN-γ, IL-18 and MCP-1 (P ≤ 0.02). UTI complicated with struvite formation was characterized by an exaggerated immune response that was mostly neutrophilic (P ≤ 0.0001), with lesions that showed extensive uroepithelial hyperplasia (P ≤ 0.0001), and a predominance of IL-1α, IL-1β, and GRO/KC in the urine (P ≤ 0.02). Animals with asymptomatic UTI also had a significantly high rate of kidney infection (P ≤ 0.0005). CONCLUSION: Complications associated with U. parvum infection are primarily dependent upon host-specific factors rather than Ureaplasma microbial load. The immune response in F344 rats is similar to that which occurs in humans with ureaplasmal associated disease. Therefore, this model of infection is a useful tool for elucidating U. parvum-host interactions that confer UTI and disease.",2009 Jan 26,"['Reyes, Leticia', 'Reinhard, Mary', 'Brown, Mary B']",BMC Infect Dis,,,True
ef872b80cf38917f64c42bfa52a57beb4399897a,PMC,Multivalent HA DNA Vaccination Protects against Highly Pathogenic H5N1 Avian Influenza Infection in Chickens and Mice,http://dx.doi.org/10.1371/journal.pone.0002432,PMC2657001,19293944,CC0,"BACKGROUND: Sustained outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in chickens would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses. METHODOLOGY / PRINCIPAL FINDINGS: The ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. These vaccines elicited antibodies that neutralized multiple strains of HPAI H5N1 when given in combinations containing up to 10 HAs. The response was dose-dependent, and breadth was determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA vaccines were tested first in mice and conferred protection against lethal H5N1 A/Vietnam/1203/2004 challenge 68 weeks after vaccination. In chickens, protection was observed against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 µg DNA given twice either by intramuscular needle injection or with a needle-free device. CONCLUSIONS/SIGNIFICANCE: DNA vaccines offer a generic approach to influenza virus immunization applicable to multiple animal species. In addition, the ability to substitute plasmids encoding different strains enables rapid adaptation of the vaccine to newly evolving field isolates.",2008 Jun 18,"['Rao, Srinivas', 'Kong, Wing-Pui', 'Wei, Chih-Jen', 'Yang, Zhi-Yong', 'Nason, Martha', 'Styles, Darrel', 'DeTolla, Louis J.', 'Sorrell, Erin M.', 'Song, Haichen', 'Wan, Hongquan', 'Ramirez-Nieto, Gloria C.', 'Perez, Daniel', 'Nabel, Gary J.']",PLoS One,,,True
60bc864d9515f3919e673bf5eeadfbd60ef84770,PMC,Immunohistochemistry for detection of avian infectious bronchitis virus strain M41 in the proventriculus and nervous system of experimentally infected chicken embryos,http://dx.doi.org/10.1186/1743-422X-6-15,PMC2657138,19196466,CC BY,"BACKGROUND: Infectious bronchitis virus primarily induces a disease of the respiratory system, different IBV strains may show variable tissue tropisms and also affect the oviduct and the kidneys. Proventriculitis was also associated with some new IBV strains. Aim of this study was to investigate by immunohistochemistry (IHC) the tissue tropism of avian infectious bronchitis virus (IBV) strain M41 in experimentally infected chicken embryos. RESULTS: To this end chicken embryos were inoculated in the allantoic sac with 10(3 )EID(50 )of IBV M41 at 10 days of age. At 48, 72, and 120 h postinoculation (PI), embryos and chorioallantoic membranes (CAM) were sampled, fixed, and paraffin-wax embedded. Allantoic fluid was also collected and titrated in chicken embryo kidney cells (CEK). The sensitivity of IHC in detecting IBV antigens in the CAM of inoculated eggs matched the virus reisolation and detection in CEK. Using IHC, antigens of IBV were detected in nasal epithelium, trachea, lung, spleen, myocardial vasculature, liver, gastrointestinal tract, kidney, skin, sclera of the eye, spinal cord, as well as in brain neurons of the inoculated embryos. These results were consistent with virus isolation and denote the wide tissue tropism of IBV M41 in the chicken embryo. Most importantly, we found infection of vasculature and smooth muscle of the proventriculus which has not seen before with IBV strain M41. CONCLUSION: IHC can be an additional useful tool for diagnosis of IBV infection in chickens and allows further studies to foster a deeper understanding of the pathogenesis of infections with IBV strains of different virulence. Moreover, these results underline that embryonic tissues in addition to CAM could be also used as possible source to generate IBV antigens for diagnostic purposes.",2009 Feb 5,"['Abdel-Moneim, Ahmed S', 'Zlotowski, Priscila', 'Veits, Jutta', 'Keil, Günther M', 'Teifke, Jens P']",Virol J,,,True
b23a403b1daf18cd8a06665ad3111e92453bd61b,PMC,Metabolite profiling studies in Saccharomyces cerevisiae: an assisting tool to prioritize host targets for antiviral drug screening,http://dx.doi.org/10.1186/1475-2859-8-12,PMC2658664,19183481,CC BY,"BACKGROUND: The cellular proteins Pat1p, Lsm1p, and Dhh1p are required for the replication of some positive-strand viruses and therefore are potential targets for new antiviral drugs. To prioritize host targets for antiviral drug screening a comparative metabolome analysis in Saccharomyces cerevisiae reference strain BY4742 Matα his3Δ1 leu2Δ0 lys2Δ0 ura3Δ0 and deletion strains pat1Δ, lsm1Δ and dhh1Δ was performed. RESULTS: GC/MS analysis permitted the quantification of 47 polar metabolites and the identification of 41 of them. Metabolites with significant variation between the strains were identified using partial least squares to latent structures discriminate analysis (PLS-DA). The analysis revealed least differences of pat1Δ to the reference strain as characterized by Euclidian distance of normalized peak areas. The growth rate and specific production rates of ethanol and glycerol were also most similar with this strain. CONCLUSION: From these results we hypothesize that the human analog of yeast Pat1p is most likely the best drug target candidate.",2009 Jan 30,"['Schneider, Konstantin', 'Krömer, Jens Olaf', 'Wittmann, Christoph', 'Alves-Rodrigues, Isabel', 'Meyerhans, Andreas', 'Diez, Juana', 'Heinzle, Elmar']",Microb Cell Fact,,,True
5229e54b1866448ee22e138bb7c12ab67547ccac,PMC,Host-Species Transferrin Receptor 1 Orthologs Are Cellular Receptors for Nonpathogenic New World Clade B Arenaviruses,http://dx.doi.org/10.1371/journal.ppat.1000358,PMC2658809,19343214,CC0,"The ability of a New World (NW) clade B arenavirus to enter cells using human transferrin receptor 1 (TfR1) strictly correlates with its ability to cause hemorrhagic fever. Amapari (AMAV) and Tacaribe (TCRV), two nonpathogenic NW clade B arenaviruses that do not use human TfR1, are closely related to the NW arenaviruses that cause hemorrhagic fevers. Here we show that pseudotyped viruses bearing the surface glycoprotein (GP) of AMAV or TCRV can infect cells using the TfR1 orthologs of several mammalian species, including those of their respective natural hosts, the small rodent Neacomys spinosus and the fruit bat Artibeus jamaicensis. Mutation of one residue in human TfR1 makes it a functional receptor for TCRV, and mutation of four residues makes it a functional receptor for AMAV. Our data support an in vivo role for TfR1 in the replication of most, if not all, NW clade B arenaviruses, and suggest that with modest changes in their GPs the nonpathogenic arenaviruses could use human TfR1 and emerge as human pathogens.",2009 Apr 3,"['Abraham, Jonathan', 'Kwong, Jo Ann', 'Albariño, César G.', 'Lu, Jiajie G.', 'Radoshitzky, Sheli R.', 'Salazar-Bravo, Jorge', 'Farzan, Michael', 'Spiropoulou, Christina F.', 'Choe, Hyeryun']",PLoS Pathog,,,True
27869d617d1c3766400b9f33f31e28f8fb1bdbd0,PMC,Understanding Haemophilus parasuis infection in porcine spleen through a transcriptomics approach,http://dx.doi.org/10.1186/1471-2164-10-64,PMC2660370,19196461,CC BY,"BACKGROUND: Haemophilus parasuis (HPS) is an important swine pathogen that causes Glässer's disease, which is characterized by fibrinous polyserositis, meningitis and arthritis. The molecular mechanisms that underlie the pathogenesis of the disease remain poorly understood, particularly the resistance of porcine immune system to HPS invasion. In this study, we investigated the global changes in gene expression in the spleen following HPS infection using the Affymetrix Porcine Genechip™. RESULTS: A total of 931 differentially expressed (DE) transcripts were identified in the porcine spleen 7 days after HPS infection; of these, 92 unique genes showed differential expression patterns based on analysis using BLASTX and Gene Ontology. The DE genes involved in the immune response included genes for inflammasomes (RETN, S100A8, S100A9, S100A12), adhesion molecules (CLDN3, CSPG2, CD44, LGALS8), transcription factors (ZBTB16, SLC39A14, CEBPD, CEBPB), acute-phase proteins and complement (SAA1, LTF, HP, C3), differentiation genes for epithelial cells and keratinocytes (TGM1, MS4A8B, CSTA), and genes related to antigen processing and presentation (HLA-B, HLA-DRB1). Further immunostimulation analyses indicated that mRNA levels of S100A8, S100A9, and S100A12 in porcine PK-15 cells increased within 48 h and were sustained after administration of lipopolysaccharide (LPS) and Poly(I:C) respectively. In addition, mapping of DE genes to porcine health traits QTL regions showed that 70 genes were distributed in 7 different known porcine QTL regions. Finally, 10 DE genes were validated by quantitative PCR. CONCLUSION: Our findings demonstrate previously unrecognized changes in gene transcription that are associated with HPS infection in vivo, and many potential cascades identified in the study clearly merit further investigation. Our data provide new clues to the nature of the immune response in mammals, and we have identified candidate genes that are related to resistance to HPS.",2009 Feb 5,"['Chen, Hongbo', 'Li, Changchun', 'Fang, Mingdi', 'Zhu, Mengjin', 'Li, Xinyun', 'Zhou, Rui', 'Li, Kui', 'Zhao, Shuhong']",BMC Genomics,,,True
aec5514aada77bb18c23a36f314ce949ba0ff846,PMC,"""Will they just pack up and leave?"" – attitudes and intended behaviour of hospital health care workers during an influenza pandemic",http://dx.doi.org/10.1186/1472-6963-9-30,PMC2661074,19216792,CC BY,"BACKGROUND: There is a general consensus that another influenza pandemic is inevitable. Although health care workers (HCWs) are essential to the health system response, there are few studies exploring HCW attitudes to pandemic influenza. The aim of this study was to explore HCWs knowledge, attitudes and intended behaviour towards pandemic influenza. METHODS: Cross-sectional investigation of a convenience sample of clinical and non-clinical HCWs from two tertiary-referral teaching hospitals in Sydney, Australia was conducted between June 4 and October 19, 2007. The self-administered questionnaire was distributed to hospital personal from 40 different wards and departments. The main outcome measures were intentions regarding work attendance and quarantine, antiviral use and perceived preparation. RESULTS: Respondents were categorized into four main groups by occupation: Nursing (47.5%), Medical (26.0%), Allied (15.3%) and Ancillary (11.2%). Our study found that most HCWs perceived pandemic influenza to be very serious (80.9%, n = 873) but less than half were able to correctly define it (43.9%, n = 473). Only 24.8% of respondents believed their department to be prepared for a pandemic, but nonetheless most were willing to work during a pandemic if a patient or colleague had influenza. The main determinants of variation in our study were occupational factors, demographics and health beliefs. Non-clinical staff were significantly most likely to be unsure of their intentions (OR 1.43, p < 0.001). Only 42.5% (n = 459) of respondents considered that neuraminidase inhibitor antiviral medications (oseltamivir/zanamivir) would protect them against pandemic influenza, whereas 77.5% (n = 836) believed that vaccination would be of benefit. CONCLUSION: We identified two issues that could undermine the best of pandemic plans – the first, a low level of confidence in antivirals as an effective measure; secondly, that non-clinical workers are an overlooked group whose lack of knowledge and awareness could undermine pandemic plans. Other issues included a high level of confidence in dietary measures to protect against influenza, and a belief among ancillary workers that antibiotics would be protective. All health care worker strategies should include non clinical and ancillary staff to ensure adequate business continuity for hospitals. HCW education, psychosocial support and staff communication could improve knowledge of appropriate pandemic interventions and confidence in antivirals.",2009 Feb 13,"['Seale, Holly', 'Leask, Julie', 'Po, Kieren', 'MacIntyre, C Raina']",BMC Health Serv Res,,,True
2fba918741f8128e992b17b14c8a631b36801e3f,PMC,Interferon-gamma coordinates CCL3-mediated neutrophil recruitment in vivo,http://dx.doi.org/10.1186/1471-2172-10-14,PMC2662797,19298652,CC BY,"BACKGROUND: We have shown previously that acute infection with the respiratory pathogen, pneumonia virus of mice (PVM), results in local production of the proinflammatory chemokine, CCL3, and that neutrophil recruitment in response to PVM infection is reduced dramatically in CCL3 -/- mice. RESULTS: In this work, we demonstrate that CCL3-mediated neutrophil recruitment is coordinated by interferon-gamma (IFNγ). Neutrophil recruitment in response to PVM infection was diminished five-fold in IFNγ receptor gene-deleted mice, although neutrophils from IFNγR -/- mice expressed transcripts for the CCL3 receptor, CCR1 and responded functionally to CCL3 ex vivo. Similarly, in the absence of PVM infection, CCL3 overexpression alone could not elicit neutrophil recruitment in the absence of IFNγ. Interestingly, although supplemental IFNγ restored neutrophil recruitment and resulted in a sustained weight loss among CCL3-overexpressing IFNγ -/- mice, CCL3-mediated neutrophil recruitment alone did not result in the pulmonary edema or respiratory failure characteristic of severe viral infection, suggesting that CCL3 and IFN-γ together are sufficient to promote neutrophil recruitment but not pathologic activation. CONCLUSION: Our findings reveal a heretofore unrecognized hierarchical interaction between the IFNγ and CCL3, which demonstrate that IFNγ is crucial for CCL3-mediated neutrophil recruitment in vivo.",2009 Mar 19,"['Bonville, Cynthia A', 'Percopo, Caroline M', 'Dyer, Kimberly D', 'Gao, Jiliang', 'Prussin, Calman', 'Foster, Barbara', 'Rosenberg, Helene F', 'Domachowske, Joseph B']",BMC Immunol,,,True
aed44d8b5c29a7cdf02ed56dc2cbac07dd1d6eed,PMC,Hemoglobin Cleavage Site-Specificity of the Plasmodium falciparum Cysteine Proteases Falcipain-2 and Falcipain-3,http://dx.doi.org/10.1371/journal.pone.0005156,PMC2663817,19357776,CC BY,"The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Hemoglobin hydrolysis has been described as an ordered process initiated by aspartic proteases, but cysteine protease inhibitors completely block the process, suggesting that cysteine proteases can also initiate hemoglobin hydrolysis. To characterize the specific roles of falcipains, we used three approaches. First, using random P(1) – P(4) amino acid substrate libraries, falcipain-2 and falcipain-3 demonstrated strong preference for cleavage sites with Leu at the P(2) position. Second, with overlapping peptides spanning α and β globin and proteolysis-dependent (18)O labeling, hydrolysis was seen at many cleavage sites. Third, with intact hemoglobin, numerous cleavage products were identified. Our results suggest that hemoglobin hydrolysis by malaria parasites is not a highly ordered process, but rather proceeds with rapid cleavage by falcipains at multiple sites. However, falcipain-2 and falcipain-3 show strong specificity for P(2) Leu in small peptide substrates, in agreement with the specificity in optimized small molecule inhibitors that was identified previously. These results are consistent with a principal role of falcipain-2 and falcipain-3 in the hydrolysis of hemoglobin by P. falciparum and with the possibility of developing small molecule inhibitors with optimized specificity as antimalarial agents.",2009 Apr 9,"['Subramanian, Shoba', 'Hardt, Markus', 'Choe, Youngchool', 'Niles, Richard K.', 'Johansen, Eric B.', 'Legac, Jennifer', 'Gut, Jiri', 'Kerr, Iain D.', 'Craik, Charles S.', 'Rosenthal, Philip J.']",PLoS One,,,True
710bf21a0b14c7512f2680ba1413c518432d7278,PMC,A Novel Bocavirus Associated with Acute Gastroenteritis in Australian Children,http://dx.doi.org/10.1371/journal.ppat.1000391,PMC2663820,19381259,CC BY,"Acute gastroenteritis (AGE) is a common illness affecting all age groups worldwide, causing an estimated three million deaths annually. Viruses such as rotavirus, adenovirus, and caliciviruses are a major cause of AGE, but in many patients a causal agent cannot be found despite extensive diagnostic testing. Proposing that novel viruses are the reason for this diagnostic gap, we used molecular screening to investigate a cluster of undiagnosed cases that were part of a larger case control study into the etiology of pediatric AGE. Degenerate oligonucleotide primed (DOP) PCR was used to non-specifically amplify viral DNA from fecal specimens. The amplified DNA was then cloned and sequenced for analysis. A novel virus was detected. Elucidation and analysis of the genome indicates it is a member of the Bocavirus genus of the Parvovirinae, 23% variant at the nucleotide level from its closest formally recognized relative, the Human Bocavirus (HBoV), and similar to the very recently proposed second species of Bocavirus (HBoV2). Fecal samples collected from case control pairs during 2001 for the AGE study were tested with a bocavirus-specific PCR, and HBoV2 (sequence confirmed) was detected in 32 of 186 cases with AGE (prevalence 17.2%) compared with only 15 controls (8.1%). In this same group of children, HBoV2 prevalence was exceeded only by rotavirus (39.2%) and astrovirus (21.5%) and was more prevalent than norovirus genogroup 2 (13.4%) and adenovirus (4.8%). In a univariate analysis of the matched pairs (McNemar's Test), the odds ratio for the association of AGE with HBoV2 infection was 2.6 (95% confidence interval 1.2–5.7); P = 0.007. During the course of this screening, a second novel bocavirus was detected which we have designated HBoV species 3 (HBoV3). The prevalence of HBoV3 was low (2.7%), and it was not associated with AGE. HBoV2 and HBoV3 are newly discovered bocaviruses, of which HBoV2 is the thirdmost-prevalent virus, after rotavirus and astrovirus, associated with pediatric AGE in this study.",2009 Apr 17,"['Arthur, Jane L.', 'Higgins, Geoffrey D.', 'Davidson, Geoffrey P.', 'Givney, Rodney C.', 'Ratcliff, Rodney M.']",PLoS Pathog,,,True
1eef10e356884a9f63b17f13df74ac185700ab06,PMC,What can health care professionals in the United Kingdom learn from Malawi?,http://dx.doi.org/10.1186/1478-4491-7-26,PMC2666626,19327137,CC BY,"Debate on how resource-rich countries and their health care professionals should help the plight of sub-Saharan Africa appears locked in a mind-set dominated by gloomy statistics and one-way monetary aid. Having established a project to link primary care clinics based on two-way sharing of education rather than one-way aid, our United Kingdom colleagues often ask us: ""But what can we learn from Malawi?"" A recent fact-finding visit to Malawi helped us clarify some aspects of health care that may be of relevance to health care professionals in the developed world, including the United Kingdom. This commentary article is focused on encouraging debate and discussion as to how we might wish to re-think our relationship with colleagues in other health care environments and consider how we can work together on a theme of two-way shared learning rather than one-way aid.",2009 Mar 27,"['Neville, Ron', 'Neville, Jemma']",Hum Resour Health,,,True
cdbdc0b6176729a11ba5e08c708408592d189657,PMC,Spatial analysis of falls in an urban community of Hong Kong,http://dx.doi.org/10.1186/1476-072X-8-14,PMC2666650,19291326,CC BY,"BACKGROUND: Falls are an issue of great public health concern. This study focuses on outdoor falls within an urban community in Hong Kong. Urban environmental hazards are often place-specific and dependent upon the built features, landscape characteristics, and habitual activities. Therefore, falls must be examined with respect to local situations. RESULTS: This paper uses spatial analysis methods to map fall occurrences and examine possible environmental attributes of falls in an urban community of Hong Kong. The Nearest neighbour hierarchical (Nnh) and Standard Deviational Ellipse (SDE) techniques can offer additional insights about the circumstances and environmental factors that contribute to falls. The results affirm the multi-factorial nature of falls at specific locations and for selected groups of the population. CONCLUSION: The techniques to detect hot spots of falls yield meaningful results that enable the identification of high risk locations. The combined use of descriptive and spatial analyses can be beneficial to policy makers because different preventive measures can be devised based on the types of environmental risk factors identified. The analyses are also important preludes to establishing research hypotheses for more focused studies.",2009 Mar 17,"['Lai, Poh C', 'Low, Chien T', 'Wong, Martin', 'Wong, Wing C', 'Chan, Ming H']",Int J Health Geogr,,,True
844b876f1636f5d031fe856cd7a63ae5f5c11fe7,PMC,The impact of surfactant protein-A on ozone-induced changes in the mouse bronchoalveolar lavage proteome,http://dx.doi.org/10.1186/1477-5956-7-12,PMC2666657,19323824,CC BY,"BACKGROUND: Ozone is a major component of air pollution. Exposure to this powerful oxidizing agent can cause or exacerbate many lung conditions, especially those involving innate immunity. Surfactant protein-A (SP-A) plays many roles in innate immunity by participating directly in host defense as it exerts opsonin function, or indirectly via its ability to regulate alveolar macrophages and other innate immune cells. The mechanism(s) responsible for ozone-induced pathophysiology, while likely related to oxidative stress, are not well understood. METHODS: We employed 2-dimensional difference gel electrophoresis (2D-DIGE), a discovery proteomics approach, coupled with MALDI-ToF/ToF to compare the bronchoalveolar lavage (BAL) proteomes in wild type (WT) and SP-A knockout (KO) mice and to assess the impact of ozone or filtered air on the expression of BAL proteins. Using the PANTHER database and the published literature most identified proteins were placed into three functional groups. RESULTS: We identified 66 proteins and focused our analysis on these proteins. Many of them fell into three categories: defense and immunity; redox regulation; and protein metabolism, modification and chaperones. In response to the oxidative stress of acute ozone exposure (2 ppm; 3 hours) there were many significant changes in levels of expression of proteins in these groups. Most of the proteins in the redox group were decreased, the proteins involved in protein metabolism increased, and roughly equal numbers of increases and decreases were seen in the defense and immunity group. Responses between WT and KO mice were similar in many respects. However, the percent change was consistently greater in the KO mice and there were more changes that achieved statistical significance in the KO mice, with levels of expression in filtered air-exposed KO mice being closer to ozone-exposed WT mice than to filtered air-exposed WT mice. CONCLUSION: We postulate that SP-A plays a role in reactive oxidant scavenging in WT mice and that its absence in the KO mice in the presence or absence of ozone exposure results in more pronounced, and presumably chronic, oxidative stress.",2009 Mar 26,"['Haque, Rizwanul', 'Umstead, Todd M', 'Freeman, Willard M', 'Floros, Joanna', 'Phelps, David S']",Proteome Sci,,,True
58ebd3ddb3543355def684c9762e4e24388c61bb,PMC,Which preventive measures might protect health care workers from SARS?,http://dx.doi.org/10.1186/1471-2458-9-81,PMC2666722,19284644,CC BY,"BACKGROUND: Despite the use of a series of preventive measures, a high incidence of severe acute respiratory syndrome (SARS) was observed among health care workers (HCWs) during the SARS epidemic. This study aimed to determine which preventive measures may have been effective in protecting HCWs from infection, and which were not effective. METHODS: A retrospective study was performed among 758 'frontline' health care workers who cared for SARS patients at the Second Affiliated Hospital and the Third Affiliated Hospital of Sun Yat-sen University. The HCWs with IgG against SARS and those without IgG against SARS were respectively defined as the ""case group"" and the ""control group"", and logistic regression was conducted to explore the risk factors for SARS infection in HCWs. RESULTS: After adjusting for age, gender, marital status, educational level, professional title, and the department in which an individual worked, the results of a multivariate logistic regression analysis indicated that incidence of SARS among HCWs was significantly and positively associated with: performing tracheal intubations for SARS patients, methods used for air ventilation in wards, avoiding face-to-face interaction with SARS patients, the number of pairs of gloves worn by HCWs, and caring for serious SARS cases. CONCLUSION: Some measures, particularly good air ventilation in SARS wards, may be effective in minimizing or preventing SARS transmission among HCWs in hospitals.",2009 Mar 13,"['Chen, Wei-Qing', 'Ling, Wen-Hua', 'Lu, Ci-Yong', 'Hao, Yuan-Tao', 'Lin, Zhong-Ning', 'Ling, Li', 'Huang, Jian', 'Li, Gang', 'Yan, Guang-Mei']",BMC Public Health,,,True
aea331cddd5eef46512ecea34503ed02af95d23e,PMC,Proteolytic processing of a precursor protein for a growth-promoting peptide by a subtilisin serine protease in Arabidopsis,http://dx.doi.org/10.1111/j.1365-313X.2008.03598.x,PMC2667306,18643977,CC BY,"Phytosulfokines (PSKs) are secreted, sulfated peptide hormones derived from larger prepropeptide precursors. Proteolytic processing of one of the precursors, AtPSK4, was demonstrated by cleavage of a preproAtPSK4–myc transgene product to AtPSK4–myc. Cleavage of proAtPSK4 was induced by placing root explants in tissue culture. The processing of proAtPSK4 was dependent on AtSBT1.1, a subtilisin-like serine protease, encoded by one of 56 subtilase genes in Arabidopsis. The gene encoding AtSBT1.1 was up-regulated following the transfer of root explants to tissue culture, suggesting that activation of the proteolytic machinery that cleaves proAtPSK4 is dependent on AtSBT1.1 expression. We also demonstrated that a fluorogenic peptide representing the putative subtilase recognition site in proAtPSK4 is cleaved in vitro by affinity-purified AtSBT1.1. An alanine scan through the recognition site peptide indicated that AtSBT1.1 is fairly specific for the AtPSK4 precursor. Thus, this peptide growth factor, which promotes callus formation in culture, is proteolytically cleaved from its precursor by a specific plant subtilase encoded by a gene that is up-regulated during the process of transfering root explants to tissue culture.",2008 Oct 1,"['Srivastava, Renu', 'Liu, Jian-Xiang', 'Howell, Stephen H']",Plant J,,,True
e0eb2e56b8dcac84960183ca6af7a43130064de4,PMC,Proteolytic processing of a precursor protein for a growth-promoting peptide by a subtilisin serine protease in Arabidopsis,http://dx.doi.org/10.1111/j.1365-313X.2008.03598.x,PMC2667306,18643977,CC BY,"Phytosulfokines (PSKs) are secreted, sulfated peptide hormones derived from larger prepropeptide precursors. Proteolytic processing of one of the precursors, AtPSK4, was demonstrated by cleavage of a preproAtPSK4–myc transgene product to AtPSK4–myc. Cleavage of proAtPSK4 was induced by placing root explants in tissue culture. The processing of proAtPSK4 was dependent on AtSBT1.1, a subtilisin-like serine protease, encoded by one of 56 subtilase genes in Arabidopsis. The gene encoding AtSBT1.1 was up-regulated following the transfer of root explants to tissue culture, suggesting that activation of the proteolytic machinery that cleaves proAtPSK4 is dependent on AtSBT1.1 expression. We also demonstrated that a fluorogenic peptide representing the putative subtilase recognition site in proAtPSK4 is cleaved in vitro by affinity-purified AtSBT1.1. An alanine scan through the recognition site peptide indicated that AtSBT1.1 is fairly specific for the AtPSK4 precursor. Thus, this peptide growth factor, which promotes callus formation in culture, is proteolytically cleaved from its precursor by a specific plant subtilase encoded by a gene that is up-regulated during the process of transfering root explants to tissue culture.",2008 Oct 1,"['Srivastava, Renu', 'Liu, Jian-Xiang', 'Howell, Stephen H']",Plant J,,,False
bd0a970593b33e212262cce0e5a9be28b555f18e,PMC,Conducting Research in Disease Outbreaks,http://dx.doi.org/10.1371/journal.pntd.0000335,PMC2669128,19399167,CC BY,,2009 Apr 28,"['Macklin, Ruth', 'Cowan, Ethan']",PLoS Negl Trop Dis,,,True
bc4e3f1afdbc64641df9ffa7707910d13014d529,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,True
38f132558364bdc7b9d8c509641d8aa15cfc6e62,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
898b2d11e25f2f6ccc7dab4b572f6c6f0628639f,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
ca5f8c2caf2ab03fcb4a59770cf9f319d87123ea,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
225a753b7007314d6d5c1afd339b30d032f33c7d,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
794abd55244633dadcc6a225ff7c8f0d551e3a66,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
24cd9a024288d5259cb0a8d140efa70a25f73bc0,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
59e9689301d4f10b7d2d5cc6d183ec23afcfcc98,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
854484745a732a6229fe917030fd35198ffac799,PMC,Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin,http://dx.doi.org/10.1371/journal.ppat.1000417,PMC2670497,19412526,CC BY,"Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.",2009 May 1,"['Koudelka, Kristopher J.', 'Destito, Giuseppe', 'Plummer, Emily M.', 'Trauger, Sunia A.', 'Siuzdak, Gary', 'Manchester, Marianne']",PLoS Pathog,,,False
bd55c44a2d6e3ec7d067fd6c46d569e4cc869d70,PMC,Quarantine for pandemic influenza control at the borders of small island nations,http://dx.doi.org/10.1186/1471-2334-9-27,PMC2670846,19284571,CC BY,"BACKGROUND: Although border quarantine is included in many influenza pandemic plans, detailed guidelines have yet to be formulated, including considerations for the optimal quarantine length. Motivated by the situation of small island nations, which will probably experience the introduction of pandemic influenza via just one airport, we examined the potential effectiveness of quarantine as a border control measure. METHODS: Analysing the detailed epidemiologic characteristics of influenza, the effectiveness of quarantine at the borders of islands was modelled as the relative reduction of the risk of releasing infectious individuals into the community, explicitly accounting for the presence of asymptomatic infected individuals. The potential benefit of adding the use of rapid diagnostic testing to the quarantine process was also considered. RESULTS: We predict that 95% and 99% effectiveness in preventing the release of infectious individuals into the community could be achieved with quarantine periods of longer than 4.7 and 8.6 days, respectively. If rapid diagnostic testing is combined with quarantine, the lengths of quarantine to achieve 95% and 99% effectiveness could be shortened to 2.6 and 5.7 days, respectively. Sensitivity analysis revealed that quarantine alone for 8.7 days or quarantine for 5.7 days combined with using rapid diagnostic testing could prevent secondary transmissions caused by the released infectious individuals for a plausible range of prevalence at the source country (up to 10%) and for a modest number of incoming travellers (up to 8000 individuals). CONCLUSION: Quarantine at the borders of island nations could contribute substantially to preventing the arrival of pandemic influenza (or at least delaying the arrival date). For small island nations we recommend consideration of quarantine alone for 9 days or quarantine for 6 days combined with using rapid diagnostic testing (if available).",2009 Mar 11,"['Nishiura, Hiroshi', 'Wilson, Nick', 'Baker, Michael G']",BMC Infect Dis,,,True
74f823e968a2920c96c87977da7289f5363979da,PMC,Molecular Mechanisms of Recombination Restriction in the Envelope Gene of the Human Immunodeficiency Virus,http://dx.doi.org/10.1371/journal.ppat.1000418,PMC2671596,19424420,CC BY,"The ability of pathogens to escape the host's immune response is crucial for the establishment of persistent infections and can influence virulence. Recombination has been observed to contribute to this process by generating novel genetic variants. Although distinctive recombination patterns have been described in many viral pathogens, little is known about the influence of biases in the recombination process itself relative to selective forces acting on newly formed recombinants. Understanding these influences is important for determining how recombination contributes to pathogen genome and proteome evolution. Most previous research on recombination-driven protein evolution has focused on relatively simple proteins, usually in the context of directed evolution experiments. Here, we study recombination in the envelope gene of HIV-1 between primary isolates belonging to subtypes that recombine naturally in the HIV/AIDS pandemic. By characterizing the early steps in the generation of recombinants, we provide novel insights into the evolutionary forces that shape recombination patterns within viral populations. Specifically, we show that the combined effects of mechanistic processes that determine the locations of recombination breakpoints across the HIV-1 envelope gene, and purifying selection acting against dysfunctional recombinants, can explain almost the entire distribution of breakpoints found within this gene in nature. These constraints account for the surprising paucity of recombination breakpoints found in infected individuals within this highly variable gene. Thus, the apparent randomness of HIV evolution via recombination may in fact be relatively more predictable than anticipated. In addition, the dominance of purifying selection in localized areas of the HIV genome defines regions where functional constraints on recombinants appear particularly strong, pointing to vulnerable aspects of HIV biology.",2009 May 8,"['Simon-Loriere, Etienne', 'Galetto, Roman', 'Hamoudi, Meriem', 'Archer, John', 'Lefeuvre, Pierre', 'Martin, Darren P.', 'Robertson, David L.', 'Negroni, Matteo']",PLoS Pathog,,,True
cf0dd4d9f9f906626d5bc4a01e1f1eb21806291c,PMC,Strengthening field-based training in low and middle-income countries to build public health capacity: Lessons from Australia's Master of Applied Epidemiology program,http://dx.doi.org/10.1186/1743-8462-6-5,PMC2672090,19358710,CC BY,"BACKGROUND: The International Health Regulations (2005) and the emergence and global spread of infectious diseases have triggered a re-assessment of how rich countries should support capacity development for communicable disease control in low and medium income countries (LMIC). In LMIC, three types of public health training have been tried: the university-based model; streamed training for specialised workers; and field-based programs. The first has low rates of production and teaching may not always be based on the needs and priorities of the host country. The second model is efficient, but does not accord the workers sufficient status to enable them to impact on policy. The third has the most potential as a capacity development measure for LMIC, but in practice faces challenges which may limit its ability to promote capacity development. DISCUSSION: We describe Australia's first Master of Applied Epidemiology (MAE) model (established in 1991), which uses field-based training to strengthen the control of communicable diseases. A central attribute of this model is the way it partners and complements health department initiatives to enhance workforce skills, health system performance and the evidence-base for policies, programs and practice. SUMMARY: The MAE experience throws light on ways Australia could collaborate in regional capacity development initiatives. Key needs are a shared vision for a regional approach to integrate training with initiatives that strengthen service and research, and the pooling of human, financial and technical resources. We focus on communicable diseases, but our findings and recommendations are generalisable to other areas of public health.",2009 Apr 9,"['Patel, Mahomed S', 'Phillips, Christine B']",Aust New Zealand Health Policy,,,True
0162b627476379a84d5a92480a881efdd3063f66,PMC,Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways,http://dx.doi.org/10.1371/journal.ppat.1000424,PMC2673688,19436701,CC0,"Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo. Using an in vitro model of human ciliated airway epithelium (HAE), we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37°C), avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human proximal airways (32°C). These data support the hypothesis that avian influenza viruses, ordinarily adapted to the temperature of the avian enteric tract (40°C), rarely infect humans, in part due to differences in host airway regional temperatures. Previously, a critical residue at position 627 in the avian influenza virus polymerase subunit, PB2, was identified as conferring temperature-dependency in mammalian cells. Here, we use reverse genetics to show that avianization of residue 627 attenuates a human virus, but does not account for the different infection between 32°C and 37°C. To determine the mechanism of temperature restriction of avian influenza viruses in HAE at 32°C, we generated recombinant human influenza viruses in either the A/Victoria/3/75 (H3N2) or A/PR/8/34 (H1N1) genetic background that contained avian or avian-like glycoproteins. Two of these viruses, A/Victoria/3/75 with L226Q and S228G mutations in hemagglutinin (HA) and neuraminidase (NA) from A/Chick/Italy/1347/99 and A/PR/8/34 containing the H7 and N1 from A/Chick/Italy/1347/99, exhibited temperature restriction approaching that of wholly avian influenza viruses. These data suggest that influenza viruses bearing avian or avian-like surface glycoproteins have a reduced capacity to establish productive infection at the temperature of the human proximal airways. This temperature restriction may limit zoonotic transmission of avian influenza viruses and suggests that adaptation of avian influenza viruses to efficient infection at 32°C may represent a critical evolutionary step enabling human-to-human transmission.",2009 May 15,"['Scull, Margaret A.', 'Gillim-Ross, Laura', 'Santos, Celia', 'Roberts, Kim L.', 'Bordonali, Elena', 'Subbarao, Kanta', 'Barclay, Wendy S.', 'Pickles, Raymond J.']",PLoS Pathog,,,True
3f962f74bcf72c06a4f0941b8da40742024dae3f,PMC,The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes,http://dx.doi.org/10.1371/journal.ppat.1000428,PMC2674928,19436709,CC BY,"Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV), the non-structural proteins (Nsps), have been determined. However, within the large Nsp3 (1922 amino-acid residues), the structure and function of the so-called SARS-unique domain (SUD) have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389–652 (“SUD(core)”) of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 Å resolution, respectively) revealed that SUD(core) forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUD(core) as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy- as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of G-quadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5–6 nucleotides, but more extended G-stretches are found in the 3′-nontranslated regions of mRNAs coding for certain host-cell proteins involved in apoptosis or signal transduction, and have been shown to bind to SUD in vitro. Therefore, SUD may be involved in controlling the host cell's response to the viral infection. Possible interference with poly(ADP-ribose) polymerase-like domains is also discussed.",2009 May 15,"['Tan, Jinzhi', 'Vonrhein, Clemens', 'Smart, Oliver S.', 'Bricogne, Gerard', 'Bollati, Michela', 'Kusov, Yuri', 'Hansen, Guido', 'Mesters, Jeroen R.', 'Schmidt, Christian L.', 'Hilgenfeld, Rolf']",PLoS Pathog,,,True
cfd27fc9582d326ef3b09be615d649e3b6e85c61,PMC,The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes,http://dx.doi.org/10.1371/journal.ppat.1000428,PMC2674928,19436709,CC BY,"Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV), the non-structural proteins (Nsps), have been determined. However, within the large Nsp3 (1922 amino-acid residues), the structure and function of the so-called SARS-unique domain (SUD) have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389–652 (“SUD(core)”) of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 Å resolution, respectively) revealed that SUD(core) forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUD(core) as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy- as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of G-quadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5–6 nucleotides, but more extended G-stretches are found in the 3′-nontranslated regions of mRNAs coding for certain host-cell proteins involved in apoptosis or signal transduction, and have been shown to bind to SUD in vitro. Therefore, SUD may be involved in controlling the host cell's response to the viral infection. Possible interference with poly(ADP-ribose) polymerase-like domains is also discussed.",2009 May 15,"['Tan, Jinzhi', 'Vonrhein, Clemens', 'Smart, Oliver S.', 'Bricogne, Gerard', 'Bollati, Michela', 'Kusov, Yuri', 'Hansen, Guido', 'Mesters, Jeroen R.', 'Schmidt, Christian L.', 'Hilgenfeld, Rolf']",PLoS Pathog,,,False
1560867701aecc60f73407501a5c5c85e53c8522,PMC,MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins,http://dx.doi.org/10.1371/journal.pone.0005466,PMC2674933,19404494,CC BY,"BACKGROUND: Host responses to viral infection include both immune activation and programmed cell death. The mitochondrial antiviral signaling adaptor, MAVS (IPS-1, VISA or Cardif) is critical for host defenses to viral infection by inducing type-1 interferons (IFN-I), however its role in virus-induced apoptotic responses has not been elucidated. PRINCIPAL FINDINGS: We show that MAVS causes apoptosis independent of its function in initiating IFN-I production. MAVS-induced cell death requires mitochondrial localization, is caspase dependent, and displays hallmarks of apoptosis. Furthermore, MAVS(−/−) fibroblasts are resistant to Sendai virus-induced apoptosis. A functional screen identifies the hepatitis C virus NS3/4A and the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) nonstructural protein (NSP15) as inhibitors of MAVS-induced apoptosis, possibly as a method of immune evasion. SIGNIFICANCE: This study describes a novel role for MAVS in controlling viral infections through the induction of apoptosis, and identifies viral proteins which inhibit this host response.",2009 Mar 7,"['Lei, Yu', 'Moore, Chris B.', 'Liesman, Rachael M.', ""O'Connor, Brian P."", 'Bergstralh, Daniel T.', 'Chen, Zhijian J.', 'Pickles, Raymond J.', 'Ting, Jenny P.-Y.']",PLoS One,,,True
5f8d96a8606eb6c9a89a1160f8b498c6c0efecba,PMC,Targeted Strategies for Henipavirus Therapeutics,http://dx.doi.org/10.2174/1874357900701010014,PMC2675550,19440455,CC BY,"Hendra and Nipah viruses are related emergent paramyxoviruses that infect and cause disease in animals and humans. Disease manifests as a generalized vasculitis affecting multiple organs, but is the most severe in the respiratory and central nervous systems. The high case fatality and person-to-person transmission associated with the most recent NiV outbreaks, and the recent re-emergence of HeV, emphasize the importance and necessity of effective therapeutics for these novel agents. In recent years henipavirus research has revealed a more complete understanding of pathogenesis and, as a consequence, viable approaches towards vaccines and therapeutics have emerged. All strategies target early steps in viral replication including receptor binding and membrane fusion. Animal models have been developed, some of which may prove more valuable than others for evaluating the efficacy of therapeutic agents and regimes. Assessments of protective host immunity and drug pharmacokinetics will be crucial to the further advancement of therapeutic compounds.",2007 Sep 28,"['Bossart, Katharine N', 'Bingham, John', 'Middleton, Deborah']",Open Virol J,,,True
9179c5c9df6bf1ac1aab2f413d18c1954e680fd2,PMC,Differential stepwise evolution of SARS coronavirus functional proteins in different host species,http://dx.doi.org/10.1186/1471-2148-9-52,PMC2676248,19261195,CC BY,"BACKGROUND: SARS coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and extensive investigations indicated that it originated from an animal source (probably bats) and was recently introduced into the human population via wildlife animals from wet markets in southern China. Previous studies revealed that the spike (S) protein of SARS had experienced adaptive evolution, but whether other functional proteins of SARS have undergone adaptive evolution is not known. RESULTS: We employed several methods to investigate selective pressure among different SARS-CoV groups representing different epidemic periods and hosts. Our results suggest that most functional proteins of SARS-CoV have experienced a stepwise adaptive evolutionary pathway. Similar to previous studies, the spike protein underwent strong positive selection in the early and middle phases, and became stabilized in the late phase. In addition, the replicase experienced positive selection only in human patients, whereas assembly proteins experienced positive selection mainly in the middle and late phases. No positive selection was found in any proteins of bat SARS-like-CoV. Furthermore, specific amino acid sites that may be the targets of positive selection in each group are identified. CONCLUSION: This extensive evolutionary analysis revealed the stepwise evolution of different functional proteins of SARS-CoVs at different epidemic stages and different hosts. These results support the hypothesis that SARS-CoV originated from bats and that the spill over into civets and humans were more recent events.",2009 Mar 5,"['Tang, Xianchun', 'Li, Gang', 'Vasilakis, Nikos', 'Zhang, Yuan', 'Shi, Zhengli', 'Zhong, Yang', 'Wang, Lin-Fa', 'Zhang, Shuyi']",BMC Evol Biol,,,True
c2a6c7620806625deff2f67d0b5924ac1c52499e,PMC,Differential stepwise evolution of SARS coronavirus functional proteins in different host species,http://dx.doi.org/10.1186/1471-2148-9-52,PMC2676248,19261195,CC BY,"BACKGROUND: SARS coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and extensive investigations indicated that it originated from an animal source (probably bats) and was recently introduced into the human population via wildlife animals from wet markets in southern China. Previous studies revealed that the spike (S) protein of SARS had experienced adaptive evolution, but whether other functional proteins of SARS have undergone adaptive evolution is not known. RESULTS: We employed several methods to investigate selective pressure among different SARS-CoV groups representing different epidemic periods and hosts. Our results suggest that most functional proteins of SARS-CoV have experienced a stepwise adaptive evolutionary pathway. Similar to previous studies, the spike protein underwent strong positive selection in the early and middle phases, and became stabilized in the late phase. In addition, the replicase experienced positive selection only in human patients, whereas assembly proteins experienced positive selection mainly in the middle and late phases. No positive selection was found in any proteins of bat SARS-like-CoV. Furthermore, specific amino acid sites that may be the targets of positive selection in each group are identified. CONCLUSION: This extensive evolutionary analysis revealed the stepwise evolution of different functional proteins of SARS-CoVs at different epidemic stages and different hosts. These results support the hypothesis that SARS-CoV originated from bats and that the spill over into civets and humans were more recent events.",2009 Mar 5,"['Tang, Xianchun', 'Li, Gang', 'Vasilakis, Nikos', 'Zhang, Yuan', 'Shi, Zhengli', 'Zhong, Yang', 'Wang, Lin-Fa', 'Zhang, Shuyi']",BMC Evol Biol,,,False
9d811a663f9c0c0eb76946d3dd7d11369ce5ef2a,PMC,Differential stepwise evolution of SARS coronavirus functional proteins in different host species,http://dx.doi.org/10.1186/1471-2148-9-52,PMC2676248,19261195,CC BY,"BACKGROUND: SARS coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and extensive investigations indicated that it originated from an animal source (probably bats) and was recently introduced into the human population via wildlife animals from wet markets in southern China. Previous studies revealed that the spike (S) protein of SARS had experienced adaptive evolution, but whether other functional proteins of SARS have undergone adaptive evolution is not known. RESULTS: We employed several methods to investigate selective pressure among different SARS-CoV groups representing different epidemic periods and hosts. Our results suggest that most functional proteins of SARS-CoV have experienced a stepwise adaptive evolutionary pathway. Similar to previous studies, the spike protein underwent strong positive selection in the early and middle phases, and became stabilized in the late phase. In addition, the replicase experienced positive selection only in human patients, whereas assembly proteins experienced positive selection mainly in the middle and late phases. No positive selection was found in any proteins of bat SARS-like-CoV. Furthermore, specific amino acid sites that may be the targets of positive selection in each group are identified. CONCLUSION: This extensive evolutionary analysis revealed the stepwise evolution of different functional proteins of SARS-CoVs at different epidemic stages and different hosts. These results support the hypothesis that SARS-CoV originated from bats and that the spill over into civets and humans were more recent events.",2009 Mar 5,"['Tang, Xianchun', 'Li, Gang', 'Vasilakis, Nikos', 'Zhang, Yuan', 'Shi, Zhengli', 'Zhong, Yang', 'Wang, Lin-Fa', 'Zhang, Shuyi']",BMC Evol Biol,,,False
22351fd6861be2afb9543f84031ac903e22dd0bb,PMC,Differential stepwise evolution of SARS coronavirus functional proteins in different host species,http://dx.doi.org/10.1186/1471-2148-9-52,PMC2676248,19261195,CC BY,"BACKGROUND: SARS coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and extensive investigations indicated that it originated from an animal source (probably bats) and was recently introduced into the human population via wildlife animals from wet markets in southern China. Previous studies revealed that the spike (S) protein of SARS had experienced adaptive evolution, but whether other functional proteins of SARS have undergone adaptive evolution is not known. RESULTS: We employed several methods to investigate selective pressure among different SARS-CoV groups representing different epidemic periods and hosts. Our results suggest that most functional proteins of SARS-CoV have experienced a stepwise adaptive evolutionary pathway. Similar to previous studies, the spike protein underwent strong positive selection in the early and middle phases, and became stabilized in the late phase. In addition, the replicase experienced positive selection only in human patients, whereas assembly proteins experienced positive selection mainly in the middle and late phases. No positive selection was found in any proteins of bat SARS-like-CoV. Furthermore, specific amino acid sites that may be the targets of positive selection in each group are identified. CONCLUSION: This extensive evolutionary analysis revealed the stepwise evolution of different functional proteins of SARS-CoVs at different epidemic stages and different hosts. These results support the hypothesis that SARS-CoV originated from bats and that the spill over into civets and humans were more recent events.",2009 Mar 5,"['Tang, Xianchun', 'Li, Gang', 'Vasilakis, Nikos', 'Zhang, Yuan', 'Shi, Zhengli', 'Zhong, Yang', 'Wang, Lin-Fa', 'Zhang, Shuyi']",BMC Evol Biol,,,False
61f80012b6b8ea03a65fe97eefc30480990b11be,PMC,P58(IPK): A Novel “CIHD” Member of the Host Innate Defense Response against Pathogenic Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1000438,PMC2677460,19461876,CC0,"To support their replication, viruses take advantage of numerous cellular factors and processes. Recent large-scale screens have identified hundreds of such factors, yet little is known about how viruses exploit any of these. Influenza virus infection post-translationally activates P58(IPK), a cellular inhibitor of the interferon-induced, dsRNA-activated eIF2α kinase, PKR. Here, we report that infection of P58(IPK) knockout mice with influenza virus resulted in increased lung pathology, immune cell apoptosis, PKR activation, and mortality. Analysis of lung transcriptional profiles, including those induced by the reconstructed 1918 pandemic virus, revealed increased expression of genes associated with the cell death, immune, and inflammatory responses. These experiments represent the first use of a mammalian infection model to demonstrate the role of P58(IPK) in the antiviral response. Our results suggest that P58(IPK) represents a new class of molecule, a cellular inhibitor of the host defense (CIHD), as P58(IPK) is activated during virus infection to inhibit virus-induced apoptosis and inflammation to prolong host survival, even while prolonging viral replication.",2009 May 22,"['Goodman, Alan G.', 'Fornek, Jamie L.', 'Medigeshi, Guruprasad R.', 'Perrone, Lucy A.', 'Peng, Xinxia', 'Dyer, Matthew D.', 'Proll, Sean C.', 'Knoblaugh, Sue E.', 'Carter, Victoria S.', 'Korth, Marcus J.', 'Nelson, Jay A.', 'Tumpey, Terrence M.', 'Katze, Michael G.']",PLoS Pathog,,,True
61f7459a82d39c89e72c2c8068dbb87f7652dba9,PMC,Acclimatory responses of the Daphnia pulex proteome to environmental changes. II. Chronic exposure to different temperatures (10 and 20°C) mainly affects protein metabolism,http://dx.doi.org/10.1186/1472-6793-9-8,PMC2678069,19383147,CC BY,"BACKGROUND: Temperature affects essentially every aspect of the biology of poikilothermic animals including the energy and mass budgets, activity, growth, and reproduction. While thermal effects in ecologically important groups such as daphnids have been intensively studied at the ecosystem level and at least partly at the organismic level, much less is known about the molecular mechanisms underlying the acclimation to different temperatures. By using 2D gel electrophoresis and mass spectrometry, the present study identified the major elements of the temperature-induced subset of the proteome from differently acclimated Daphnia pulex. RESULTS: Specific sets of proteins were found to be differentially expressed in 10°C or 20°C acclimated D. pulex. Most cold-repressed proteins comprised secretory enzymes which are involved in protein digestion (trypsins, chymotrypsins, astacin, carboxypeptidases). The cold-induced sets of proteins included several vitellogenin and actin isoforms (cytoplasmic and muscle-specific), and an AAA+ ATPase. Carbohydrate-modifying enzymes were constitutively expressed or down-regulated in the cold. CONCLUSION: Specific sets of cold-repressed and cold-induced proteins in D. pulex can be related to changes in the cellular demand for amino acids or to the compensatory control of physiological processes. The increase of proteolytic enzyme concentration and the decrease of vitellogenin, actin and total protein concentration between 10°C and 20°C acclimated animals reflect the increased amino-acids demand and the reduced protein reserves in the animal's body. Conversely, the increase of actin concentration in cold-acclimated animals may contribute to a compensatory mechanism which ensures the relative constancy of muscular performance. The sheer number of peptidase genes (serine-peptidase-like: > 200, astacin-like: 36, carboxypeptidase-like: 30) in the D. pulex genome suggests large-scaled gene family expansions that might reflect specific adaptations to the lifestyle of a planktonic filter feeder in a highly variable aquatic environment.",2009 Apr 21,"['Schwerin, Susanne', 'Zeis, Bettina', 'Lamkemeyer, Tobias', 'Paul, Rüdiger J', 'Koch, Marita', 'Madlung, Johannes', 'Fladerer, Claudia', 'Pirow, Ralph']",BMC Physiol,,,True
faef77dd02384453eb8aef0159dc8bf52499a071,PMC,Acclimatory responses of the Daphnia pulex proteome to environmental changes. II. Chronic exposure to different temperatures (10 and 20°C) mainly affects protein metabolism,http://dx.doi.org/10.1186/1472-6793-9-8,PMC2678069,19383147,CC BY,"BACKGROUND: Temperature affects essentially every aspect of the biology of poikilothermic animals including the energy and mass budgets, activity, growth, and reproduction. While thermal effects in ecologically important groups such as daphnids have been intensively studied at the ecosystem level and at least partly at the organismic level, much less is known about the molecular mechanisms underlying the acclimation to different temperatures. By using 2D gel electrophoresis and mass spectrometry, the present study identified the major elements of the temperature-induced subset of the proteome from differently acclimated Daphnia pulex. RESULTS: Specific sets of proteins were found to be differentially expressed in 10°C or 20°C acclimated D. pulex. Most cold-repressed proteins comprised secretory enzymes which are involved in protein digestion (trypsins, chymotrypsins, astacin, carboxypeptidases). The cold-induced sets of proteins included several vitellogenin and actin isoforms (cytoplasmic and muscle-specific), and an AAA+ ATPase. Carbohydrate-modifying enzymes were constitutively expressed or down-regulated in the cold. CONCLUSION: Specific sets of cold-repressed and cold-induced proteins in D. pulex can be related to changes in the cellular demand for amino acids or to the compensatory control of physiological processes. The increase of proteolytic enzyme concentration and the decrease of vitellogenin, actin and total protein concentration between 10°C and 20°C acclimated animals reflect the increased amino-acids demand and the reduced protein reserves in the animal's body. Conversely, the increase of actin concentration in cold-acclimated animals may contribute to a compensatory mechanism which ensures the relative constancy of muscular performance. The sheer number of peptidase genes (serine-peptidase-like: > 200, astacin-like: 36, carboxypeptidase-like: 30) in the D. pulex genome suggests large-scaled gene family expansions that might reflect specific adaptations to the lifestyle of a planktonic filter feeder in a highly variable aquatic environment.",2009 Apr 21,"['Schwerin, Susanne', 'Zeis, Bettina', 'Lamkemeyer, Tobias', 'Paul, Rüdiger J', 'Koch, Marita', 'Madlung, Johannes', 'Fladerer, Claudia', 'Pirow, Ralph']",BMC Physiol,,,False
13c8501740d1be695a284293351dd9181c0aba9a,PMC,Acclimatory responses of the Daphnia pulex proteome to environmental changes. II. Chronic exposure to different temperatures (10 and 20°C) mainly affects protein metabolism,http://dx.doi.org/10.1186/1472-6793-9-8,PMC2678069,19383147,CC BY,"BACKGROUND: Temperature affects essentially every aspect of the biology of poikilothermic animals including the energy and mass budgets, activity, growth, and reproduction. While thermal effects in ecologically important groups such as daphnids have been intensively studied at the ecosystem level and at least partly at the organismic level, much less is known about the molecular mechanisms underlying the acclimation to different temperatures. By using 2D gel electrophoresis and mass spectrometry, the present study identified the major elements of the temperature-induced subset of the proteome from differently acclimated Daphnia pulex. RESULTS: Specific sets of proteins were found to be differentially expressed in 10°C or 20°C acclimated D. pulex. Most cold-repressed proteins comprised secretory enzymes which are involved in protein digestion (trypsins, chymotrypsins, astacin, carboxypeptidases). The cold-induced sets of proteins included several vitellogenin and actin isoforms (cytoplasmic and muscle-specific), and an AAA+ ATPase. Carbohydrate-modifying enzymes were constitutively expressed or down-regulated in the cold. CONCLUSION: Specific sets of cold-repressed and cold-induced proteins in D. pulex can be related to changes in the cellular demand for amino acids or to the compensatory control of physiological processes. The increase of proteolytic enzyme concentration and the decrease of vitellogenin, actin and total protein concentration between 10°C and 20°C acclimated animals reflect the increased amino-acids demand and the reduced protein reserves in the animal's body. Conversely, the increase of actin concentration in cold-acclimated animals may contribute to a compensatory mechanism which ensures the relative constancy of muscular performance. The sheer number of peptidase genes (serine-peptidase-like: > 200, astacin-like: 36, carboxypeptidase-like: 30) in the D. pulex genome suggests large-scaled gene family expansions that might reflect specific adaptations to the lifestyle of a planktonic filter feeder in a highly variable aquatic environment.",2009 Apr 21,"['Schwerin, Susanne', 'Zeis, Bettina', 'Lamkemeyer, Tobias', 'Paul, Rüdiger J', 'Koch, Marita', 'Madlung, Johannes', 'Fladerer, Claudia', 'Pirow, Ralph']",BMC Physiol,,,False
1eb37c6ac1e51907a8a1d5f31c45fff08737cb36,PMC,Systems biology coupled with label-free high-throughput detection as a novel approach for diagnosis of chronic obstructive pulmonary disease,http://dx.doi.org/10.1186/1465-9921-10-29,PMC2678087,19386108,CC BY,"Chronic obstructive pulmonary disease (COPD) is a treatable and preventable disease state, characterised by progressive airflow limitation that is not fully reversible. Although COPD is primarily a disease of the lungs there is now an appreciation that many of the manifestations of disease are outside the lung, leading to the notion that COPD is a systemic disease. Currently, diagnosis of COPD relies on largely descriptive measures to enable classification, such as symptoms and lung function. Here the limitations of existing diagnostic strategies of COPD are discussed and systems biology approaches to diagnosis that build upon current molecular knowledge of the disease are described. These approaches rely on new 'label-free' sensing technologies, such as high-throughput surface plasmon resonance (SPR), that we also describe.",2009 Apr 22,"['Richens, Joanna L', 'Urbanowicz, Richard A', 'Lunt, Elizabeth AM', 'Metcalf, Rebecca', 'Corne, Jonathan', 'Fairclough, Lucy', ""O'Shea, Paul""]",Respir Res,,,True
aaaf05c5781726bd7c58cffa351a651580893257,PMC,Linkages between animal and human health sentinel data,http://dx.doi.org/10.1186/1746-6148-5-15,PMC2679002,19389228,CC BY,"INTRODUCTION: In order to identify priorities for building integrated surveillance systems that effectively model and predict human risk of zoonotic diseases, there is a need for improved understanding of the practical options for linking surveillance data of animals and humans. We conducted an analysis of the literature and characterized the linkage between animal and human health data. We discuss the findings in relation to zoonotic surveillance and the linkage of human and animal data. METHODS: The Canary Database, an online bibliographic database of animal-sentinel studies was searched and articles were classified according to four linkage categories. RESULTS: 465 studies were identified and assigned to linkage categories involving: descriptive, analytic, molecular, or no human outcomes of human and animal health. Descriptive linkage was the most common, whereby both animal and human health outcomes were presented, but without quantitative linkage between the two. Rarely, analytic linkage was utilized in which animal data was used to quantitatively predict human risk. The other two categories included molecular linkage, and no human outcomes, which present health outcomes in animals but not humans. DISCUSSION: We found limited use of animal data to quantitatively predict human risk and listed the methods from the literature that performed analytic linkage. The lack of analytic linkage in the literature might not be solely related to technological barriers including access to electronic database, statistical software packages, and Geographical Information System (GIS). Rather, the problem might be from a lack of understanding by researchers of the importance of animal data as a 'sentinel' for human health. Researchers performing zoonotic surveillance should be aware of the value of animal-sentinel approaches for predicting human risk and consider analytic methods for linking animal and human data. Qualitative work needs to be done in order to examine researchers' decisions in linkage strategies between animal and human data.",2009 Apr 23,"['Scotch, Matthew', 'Odofin, Lynda', 'Rabinowitz, Peter']",BMC Vet Res,,,True
3a693a23a7b7c13330611d995ea9d8861203c8b9,PMC,Wild canids as sentinels of ecological health: a conservation medicine perspective,http://dx.doi.org/10.1186/1756-3305-2-S1-S7,PMC2679399,19426446,CC BY,"The extinction of species across the globe is accelerating, directly or indirectly due to human activities. Biological impoverishment, habitat fragmentation, climate change, increasing toxification, and the rapid global movement of people and other living organisms have worked synergistically to diminish ecosystem function. This has resulted in unprecedented levels of disease emergence, driven by human-induced environmental degradation, which poses a threat to the survival and health of biodiversity. The emerging discipline of conservation medicine addresses these concerns through the following entities: humans; global climate; habitat destruction and alteration; biodiversity, including wildlife populations; domestic animals; and pathogens, parasites and pollutants. Furthermore, conservation medicine focuses on explicit linkages between these entities. As a crisis discipline, the usefulness of conservation medicine ultimately will depend on its applicability to solving problems. The perspectives and scientific findings of conservation medicine provide input into biomedical education; and policy and management of ecosystems, habitats and imperiled species. A sentinel species is one that has presented itself, or has been selected, to provide insight into the state (health) of an ecosystem, based on user-defined (e.g., researchers, conservationists or policymakers) objectives (e.g., disease, parasites, toxics, climate change, habitat destruction), coupled with the utility and vulnerability of this species to the perceived stress. The scientific information generated by the sentinel species should empower stakeholders and decision-makers to take mitigative action or support predictive capabilities; the ""utility"" of the species selected should consider its value and relevance to conservationists and to society at large (e.g., education and outreach; social sciences). Wild canids may serve as excellent sentinel species of emerging canine vector-borne diseases. Several canine vector-borne diseases or antibodies to these pathogens have been identified in wild canids including visceral leishmaniosis, Lyme disease, heartworm, hepatozoonosis and anaplasmosis to name a few. These reports are relatively recent as they relate to wildlife-domestic animal interactions, globalisation, translocations, habitat fragmentation and climate change. These pathogens and their relationship to wild canids are described herein. Further research needs to be performed to elucidate the role of the 36 extant species of wild canids in the epidemiology of canine vector-borne diseases.",2009 Mar 26,"Aguirre, A Alonso",Parasit Vectors,,,True
10fc3f71e291a910975b698e2158d15e96658bab,PMC,Autonomous Tetramerization Domains in the Glycan-binding Receptors DC-SIGN and DC-SIGNR,http://dx.doi.org/10.1016/j.jmb.2009.02.046,PMC2680971,19249311,CC BY,"Multivalent binding of glycans on pathogens and on mammalian cells by the receptors DC-SIGN (CD209) and DC-SIGNR (L-SIGN, CD299) is dependent on correct disposition of the C-type carbohydrate-recognition domains projected at the C-terminal ends of necks at the cell surface. In the work reported here, neck domains of DC-SIGN and DC-SIGNR expressed in isolation are shown to form tetramers in the absence of the CRDs. Stability analysis indicates that interactions between the neck domains account fully for the stability of the tetrameric extracellular portions of the receptors. The neck domains are approximately 40% α-helical based on circular dichroism analysis. However, in contrast to other glycan-binding receptors in which fully helical neck regions are intimately associated with C-terminal C-type CRDs, the neck domains in DC-SIGN and DC-SIGNR act as autonomous tetramerization domains and the neck domains and CRDs are organized independently. Neck domains from polymorphic forms of DC-SIGNR that lack some of the repeat sequences show modestly reduced stability, but differences near the C-terminal end of the neck domains lead to significantly enhanced stability of DC-SIGNR tetramers compared to DC-SIGN.",2009 Apr 17,"['Yu, Quan D.', 'Oldring, Asa P.', 'Powlesland, Alex S.', 'Tso, Cynthia K.W.', 'Yang, Chunxuan', 'Drickamer, Kurt', 'Taylor, Maureen E.']",J Mol Biol,,,False
920282c7a0656a43143be9b656b36367cf871c08,PMC,Combination Therapy Using Chimeric Monoclonal Antibodies Protects Mice from Lethal H5N1 Infection and Prevents Formation of Escape Mutants,http://dx.doi.org/10.1371/journal.pone.0005672,PMC2682562,19478856,CC BY,"BACKGROUND: Given that there is a possibility of a human H5N1 pandemic and the fact that the recent H5N1 viruses are resistant to the anti-viral drugs, newer strategies for effective therapy are warranted. Previous studies show that single mAbs in immune prophylaxis can be protective against H5N1 infection. But a single mAb may not be effective in neutralization of a broad range of different strains of H5N1 and control of potential neutralization escape mutants. METHODS/PRINCIPAL FINDINGS: We selected two mAbs which recognized different epitopes on the hemagglutinin molecule. These two mAbs could each neutralize in vitro escape mutants to the other and in combination could effectively neutralize viruses from clades 0, 1, 2.1, 2.2, 2.3, 4, 7 and 8 of influenza A H5N1 viruses. This combination of chimeric mAbs when administered passively, pre or post challenge with 10 MLD50 (50% mouse lethal dose) HPAI H5N1 influenza A viruses could protect 100% of the mice from two different clades of viruses (clades 1 and 2.1). We also tested the efficacy of a single dose of the combination of mAbs versus two doses. Two doses of the combination therapy not only affected early clearance of the virus from the lung but could completely prevent lung pathology of the H5N1 infected mice. No escape variants were detected after therapy. CONCLUSIONS/SIGNIFICANCE: Our studies provide proof of concept that the synergistic action of two or more mAbs in combination is required for preventing the generation of escape mutants and also to enhance the therapeutic efficacy of passive therapy against H5N1 infection. Combination therapy may allow for a lower dose of antibody to be administered for passive therapy of influenza infection and hence can be made available at reduced economic costs during an outbreak.",2009 May 22,"['Prabakaran, Mookkan', 'Prabhu, Nayana', 'He, Fang', 'Hongliang, Qian', 'Ho, Hui-Ting', 'Qiang, Jia', 'TaoMeng,', 'Goutama, Michael', 'Kwang, Jimmy']",PLoS One,,,True
404bf0836c388f561f796369c26d0bbf6f37b407,PMC,Small Interfering RNA Targeting M2 Gene Induces Effective and Long Term Inhibition of Influenza A Virus Replication,http://dx.doi.org/10.1371/journal.pone.0005671,PMC2682565,19479060,CC BY,"RNA interference (RNAi) provides a powerful new means to inhibit viral infection specifically. However, the selection of siRNA-resistant viruses is a major concern in the use of RNAi as antiviral therapeutics. In this study, we conducted a lentiviral vector with a H1-short hairpin RNA (shRNA) expression cassette to deliver small interfering RNAs (siRNAs) into mammalian cells. Using this vector that also expresses enhanced green fluorescence protein (EGFP) as surrogate marker, stable shRNA-expressing cell lines were successfully established and the inhibition efficiencies of rationally designed siRNAs targeting to conserved regions of influenza A virus genome were assessed. The results showed that a siRNA targeting influenza M2 gene (siM2) potently inhibited viral replication. The siM2 was not only effective for H1N1 virus but also for highly pathogenic avian influenza virus H5N1. In addition to its M2 inhibition, the siM2 also inhibited NP mRNA accumulation and protein expression. A long term inhibition effect of the siM2 was demonstrated and the emergence of siRNA-resistant mutants in influenza quasispecies was not observed. Taken together, our study suggested that M2 gene might be an optimal RNAi target for antiviral therapy. These findings provide useful information for the development of RNAi-based prophylaxis and therapy for human influenza virus infection.",2009 May 22,"['Sui, Hong-Yan', 'Zhao, Guang-Yu', 'Huang, Jian-Dong', 'Jin, Dong-Yan', 'Yuen, Kwok-Yung', 'Zheng, Bo-Jian']",PLoS One,,,True
20b02257b13e1631fe457bc81ed2b6033baee43e,PMC,Lack of association between polymorphisms of MASP2 and susceptibility to SARS coronavirus infection,http://dx.doi.org/10.1186/1471-2334-9-51,PMC2683852,19405982,CC BY,"BACKGROUND: The pathogenesis of severe acute respiratory disease syndrome (SARS) is not fully understood. One case-control study has reported an association between susceptibility to SARS and mannan-binding lectin (MBL) in China. As the downstream protein of MBL, variants of the MBL-associated serine protease-2 (MASP2) gene may be associated with SARS coronavirus (SARS-CoV) infection in the same population. METHODS: Thirty individuals with SARS were chosen for analysis of MASP2 polymorphisms by means of PCR direct sequencing. Tag single nucleotide polymorphisms (tagSNPs) were chosen using pairwise tagging algorithms. The frequencies of four tag SNPs (rs12711521, rs2261695, rs2273346 and rs7548659) were ascertained in 376 SARS patients and 523 control subjects, using the Beckman SNPstream Ultra High Throughput genotyping platform. RESULTS: There is no significant association between alleles or genotypes of the MASP2 tagSNP and susceptibility to SARS-CoV in both Beijing and Guangzhou populations. Diplotype (rs2273346 and rs12711521)were analyzed for association with susceptibility to SARS, no statistically significant evidence of association was observed. The Beijing and Guangzhou sample groups were homogeneous regarding demographic and genetic parameters, a joined analysis also showed no statistically significant evidence of association. CONCLUSION: Our data do not suggest a role for MASP2 polymorphisms in SARS susceptibility in northern and southern China.",2009 May 1,"['Wang, Yan', 'Yan, Jiangwei', 'Shi, Yuling', 'Li, Ping', 'Liu, Chuanxuan', 'Ma, Qingjun', 'Yang, Ruifu', 'Wang, Xiaoyi', 'zhu, Lina', 'Yang, Xiao', 'Cao, Cheng']",BMC Infect Dis,,,True
e30e44f2eb7f2effe677e665ad14ad511ac17c3f,PMC,Non-Molecular-Clock-Like Evolution following Viral Origins in Homo sapiens,,PMC2684125,19461973,CC BY,"Researchers routinely adopt molecular clock assumptions in conducting sequence analyses to estimate dates for viral origins in humans. We used computational methods to examine the extent to which this practice can result in inaccurate ‘retrodiction.’ Failing to account for dynamic molecular evolution can affect greatly estimating index case dates, resulting in an overestimated age for the SARS-CoV-human infection, for instance.",2007 Sep 26,"['Mok, Wendy', 'Seto, Kelly', 'Stone, Jon']",Evol Bioinform Online,,,True
d3b9423ca41bdd129766dce07506a87b9eec22a7,PMC,"Genome Signatures, Self-Organizing Maps and Higher Order Phylogenies: A Parametric Analysis",,PMC2684143,19468314,CC BY,"Genome signatures are data vectors derived from the compositional statistics of DNA. The self-organizing map (SOM) is a neural network method for the conceptualisation of relationships within complex data, such as genome signatures. The various parameters of the SOM training phase are investigated for their effect on the accuracy of the resulting output map. It is concluded that larger SOMs, as well as taking longer to train, are less sensitive in phylogenetic classification of unknown DNA sequences. However, where a classification can be made, a larger SOM is more accurate. Increasing the number of iterations in the training phase of the SOM only slightly increases accuracy, without improving sensitivity. The optimal length of the DNA sequence k-mer from which the genome signature should be derived is 4 or 5, but shorter values are almost as effective. In general, these results indicate that small, rapidly trained SOMs are generally as good as larger, longer trained ones for the analysis of genome signatures. These results may also be more generally applicable to the use of SOMs for other complex data sets, such as microarray data.",2007 Sep 17,"Gatherer, Derek",Evol Bioinform Online,,,True
8013bbf01944aa3f25d0faf16386ea51c7586066,PMC,Generation of Phaseolus vulgaris ESTs and investigation of their regulation upon Uromyces appendiculatus infection,http://dx.doi.org/10.1186/1471-2229-9-46,PMC2684537,19397807,CC BY,"BACKGROUND: Phaseolus vulgaris (common bean) is the second most important legume crop in the world after soybean. Consequently, yield losses due to fungal infection, like Uromyces appendiculatus (bean rust), have strong consequences. Several resistant genes were identified that confer resistance to bean rust infection. However, the downstream genes and mechanisms involved in bean resistance to infection are poorly characterized. RESULTS: A subtractive bean cDNA library composed of 10,581 unisequences was constructed and enriched in sequences regulated by either bean rust race 41, a virulent strain, or race 49, an avirulent strain on cultivar Early Gallatin carrying the resistance gene Ur-4. The construction of this library allowed the identification of 6,202 new bean ESTs, significantly adding to the available sequences for this plant. Regulation of selected bean genes in response to bean rust infection was confirmed by qRT-PCR. Plant gene expression was similar for both race 41 and 49 during the first 48 hours of the infection process but varied significantly at the later time points (72–96 hours after inoculation) mainly due to the presence of the Avr4 gene in the race 49 leading to a hypersensitive response in the bean plants. A biphasic pattern of gene expression was observed for several genes regulated in response to fungal infection. CONCLUSION: The enrichment of the public database with over 6,000 bean ESTs significantly adds to the genomic resources available for this important crop plant. The analysis of these genes in response to bean rust infection provides a foundation for further studies of the mechanism of fungal disease resistance. The expression pattern of 90 bean genes upon rust infection shares several features with other legumes infected by biotrophic fungi. This finding suggests that the P. vulgaris-U. appendiculatus pathosystem could serve as a model to explore legume-rust interaction.",2009 Apr 27,"['Thibivilliers, Sandra', 'Joshi, Trupti', 'Campbell, Kimberly B', 'Scheffler, Brian', 'Xu, Dong', 'Cooper, Bret', 'Nguyen, Henry T', 'Stacey, Gary']",BMC Plant Biol,,,True
75435342678d143b3fea48a288d1baa113d28a42,PMC,Applying the balanced scorecard to local public health performance measurement: deliberations and decisions,http://dx.doi.org/10.1186/1471-2458-9-127,PMC2684743,19426508,CC BY,"BACKGROUND: All aspects of the heath care sector are being asked to account for their performance. This poses unique challenges for local public health units with their traditional focus on population health and their emphasis on disease prevention, health promotion and protection. Reliance on measures of health status provides an imprecise and partial picture of the performance of a health unit. In 2004 the provincial Institute for Clinical Evaluative Sciences based in Ontario, Canada introduced a public-health specific balanced scorecard framework. We present the conceptual deliberations and decisions undertaken by a health unit while adopting the framework. DISCUSSION: Posing, pondering and answering key questions assisted in applying the framework and developing indicators. Questions such as: Who should be involved in developing performance indicators? What level of performance should be measured? Who is the primary intended audience? Where and how do we begin? What types of indicators should populate the health status and determinants quadrant? What types of indicators should populate the resources and services quadrant? What type of indicators should populate the community engagement quadrant? What types of indicators should populate the integration and responsiveness quadrants? Should we try to link the quadrants? What comparators do we use? How do we move from a baseline report card to a continuous quality improvement management tool? SUMMARY: An inclusive, participatory process was chosen for defining and creating indicators to populate the four quadrants. Examples of indicators that populate the four quadrants of the scorecard are presented and key decisions are highlighted that facilitated the process.",2009 May 8,"['Weir, Erica', ""d'Entremont, Nadine"", 'Stalker, Shelley', 'Kurji, Karim', 'Robinson, Victoria']",BMC Public Health,,,True
7433a628e7fe85066cddc5c25a416fea3ffa87e5,PMC,Inhibition of Lassa Virus Glycoprotein Cleavage and Multicycle Replication by Site 1 Protease-Adapted α(1)-Antitrypsin Variants,http://dx.doi.org/10.1371/journal.pntd.0000446,PMC2685025,19488405,CC BY,"BACKGROUND: Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P) is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread. Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication. METHODOLOGY/PRINCIPAL FINDING: We demonstrate that stable cell lines inducibly expressing S1P-adapted α(1)-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of α(1)-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells. Moreover, S1P-specific α(1)-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus. Inhibition of viral replication correlated with the ability of the different α(1)-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor. CONCLUSIONS/SIGNIFICANCE: Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.",2009 Jun 2,"['Maisa, Anna', 'Ströher, Ute', 'Klenk, Hans-Dieter', 'Garten, Wolfgang', 'Strecker, Thomas']",PLoS Negl Trop Dis,,,True
8f974201b04925c9627c032739f86f06cf5fdcf5,PMC,Inhibition of Lassa Virus Glycoprotein Cleavage and Multicycle Replication by Site 1 Protease-Adapted α(1)-Antitrypsin Variants,http://dx.doi.org/10.1371/journal.pntd.0000446,PMC2685025,19488405,CC BY,"BACKGROUND: Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P) is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread. Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication. METHODOLOGY/PRINCIPAL FINDING: We demonstrate that stable cell lines inducibly expressing S1P-adapted α(1)-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of α(1)-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells. Moreover, S1P-specific α(1)-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus. Inhibition of viral replication correlated with the ability of the different α(1)-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor. CONCLUSIONS/SIGNIFICANCE: Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.",2009 Jun 2,"['Maisa, Anna', 'Ströher, Ute', 'Klenk, Hans-Dieter', 'Garten, Wolfgang', 'Strecker, Thomas']",PLoS Negl Trop Dis,,,False
061f81e4132c9d443b9afa644a32fb23d75db2f7,PMC,Inhibition of Lassa Virus Glycoprotein Cleavage and Multicycle Replication by Site 1 Protease-Adapted α(1)-Antitrypsin Variants,http://dx.doi.org/10.1371/journal.pntd.0000446,PMC2685025,19488405,CC BY,"BACKGROUND: Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P) is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread. Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication. METHODOLOGY/PRINCIPAL FINDING: We demonstrate that stable cell lines inducibly expressing S1P-adapted α(1)-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of α(1)-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells. Moreover, S1P-specific α(1)-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus. Inhibition of viral replication correlated with the ability of the different α(1)-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor. CONCLUSIONS/SIGNIFICANCE: Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.",2009 Jun 2,"['Maisa, Anna', 'Ströher, Ute', 'Klenk, Hans-Dieter', 'Garten, Wolfgang', 'Strecker, Thomas']",PLoS Negl Trop Dis,,,False
a0c2551d031c6dd3f59392c3f75dffc7b694a186,PMC,T. cruzi OligoC-TesT: A Simplified and Standardized Polymerase Chain Reaction Format for Diagnosis of Chagas Disease,http://dx.doi.org/10.1371/journal.pntd.0000450,PMC2685481,19503815,CC BY,"BACKGROUND: PCR has evolved into one of the most promising tools for T. cruzi detection in the diagnosis and control of Chagas disease. However, general use of the technique is hampered by its complexity and the lack of standardization. METHODOLOGY: We here present the development and phase I evaluation of the T. cruzi OligoC-TesT, a simple and standardized dipstick format for detection of PCR amplified T. cruzi DNA. The specificity and sensitivity of the assay were evaluated on blood samples from 60 Chagas non-endemic and 48 endemic control persons and on biological samples from 33 patients, 7 reservoir animals, and 14 vectors collected in Chile. PRINCIPAL FINDINGS: The lower detection limits of the T. cruzi OligoC-TesT were 1 pg and 1 to 10 fg of DNA from T. cruzi lineage I and II, respectively. The test showed a specificity of 100% (95% confidence interval [CI]: 96.6%–100%) on the control samples and a sensitivity of 93.9% (95% CI: 80.4%–98.3%), 100% (95% CI: 64.6%–100%), and 100% (95% CI: 78.5%–100%) on the human, rodent, and vector samples, respectively. CONCLUSIONS: The T. cruzi OligoC-TesT showed high sensitivity and specificity on a diverse panel of biological samples. The new tool is an important step towards simplified and standardized molecular diagnosis of Chagas disease.",2009 Jun 2,"['Deborggraeve, Stijn', 'Coronado, Ximena', 'Solari, Aldo', 'Zulantay, Ines', 'Apt, Werner', 'Mertens, Pascal', 'Laurent, Thierry', 'Leclipteux, Thierry', 'Stessens, Tim', 'Dujardin, Jean-Claude', 'Herdewijn, Piet', 'Büscher, Philippe']",PLoS Negl Trop Dis,,,True
46ee8e5fc43eba4d4efe8979ba75a36991d9e283,PMC,The study on the outsourcing of Taiwan's hospitals: a questionnaire survey research,http://dx.doi.org/10.1186/1472-6963-9-78,PMC2685796,19435526,CC BY,"BACKGROUND: The aim of this study was to assess the outsourcing situation in Taiwanese hospitals and compares the differences in hospital ownership and in accreditation levels. METHODS: This research combined two kinds of methods: a questionnaire survey and the in-depth interview to two CEOs of the sample hospitals. One hospital is not-for-profit, while the other is a public hospital and the research samples are from the hospital data from Taiwan's 2005 to 2007 Department of Health qualifying lists of hospital accreditation. The returned questionnaires were analyzed with STATISTICA(® )7.1 version software. RESULTS: The results for non-medical items showed medical waste and common trash both have the highest rate (94.6 percent) of being outsourced. The gift store (75 percent) and linen (73 percent) follow close behind, while the lowest rate of outsourcing is in utility maintenance (13.5 percent). For medical items, the highest rate of outsourcing is in the ambulance units (51.4 percent), while the hemodialysis center follows close behind with a rate of 50 percent. For departments of nutrition, pharmacy, and nursing however, the outsourcing rate is lower than 3 percent. This shows that Taiwan's hospitals are still conservative in their willingness to outsource for medical items. The results of the satisfaction paired t-test show that the non-medical items have a higher score than the medical items. The factor analysis showed the three significant factors in of non medical items' outsourcing are ""performance"", ""finance"", and ""human resource"". For medical items, the two factors are ""operation"" and satisfaction"". To further exam the factor validity and reliability of the satisfaction model, a confirmative factor analysis (CFA) was conducted using structure equation modeling (SEM) method and found the model fitting well. CONCLUSION: Hospitals, especially for public hospitals, can get benefits from outsourcing to revive the full-time-equivalent and human resource limitation.",2009 May 13,"['Hsiao, Chih-Tung', 'Pai, Jar-Yuan', 'Chiu, Hero']",BMC Health Serv Res,,,True
5f14950df2d6d428b1dff4d58e7775f92da020d7,PMC,Detection of Colorectal Cancer by Serum and Tissue Protein Profiling: A Prospective Study in a Population at Risk,,PMC2688344,19578519,CC BY,"Colorectal cancer (CRC) is the second most common cause of cancer-related death in Europe and its prognosis is largely dependent on stage at diagnosis. Currently, there are no suitable tumour markers for early detection of CRC. In a retrospective study we previously found discriminative CRC serum protein profiles with surface enhanced laser desorption ionisation—time of flight mass spectrometry (SELDI-TOF MS). We now aimed at prospective validation of these profiles. Additionally, we assessed their applicability for follow-up after surgery and investigated tissue protein profiles of patients with CRC and adenomatous polyps (AP). Serum and tissue samples were collected from patients without known malignancy with an indication for colonoscopy and patients with AP and CRC during colonoscopy. Serum samples of controls (CON; n = 359), patients with AP (n = 177) and CRC (n = 73), as well as tissue samples from AP (n = 52) and CRC (n = 47) were analysed as described previously. Peak intensities were compared by non-parametric testing. Discriminative power of differentially expressed proteins was assessed with support vector machines (SVM). We confirmed the decreased serum levels of apolipoprotein C-1 in CRC in the current population. No differences were observed between CON and AP. Apolipoprotein C-I levels did not change significantly within 1 month post-surgery, although a gradual return to normal levels was observed. Several proteins differed between AP and CRC tissue, among which a peak with similar mass as apolipoprotein C-1. This peak was increased in CRC compared to AP. Although we prospectively validated the serum decrease of apolipoprotein C-1 in CRC, serum protein profiles did not yield SVM classifiers with suitable sensitivity and specificity for classification of our patient groups.",2008 Jul 2,"['Engwegen, Judith Y.M.N.', 'Depla, Annekatrien C.T.M.', 'Smits, Marianne E.', 'Cats, Annemieke', 'Tuynman, Henriëtte', 'van Heukelem, Henk A.', 'Snel, Pleun', 'Meuleman, Wouter', 'Wessels, Lodewyk F.', 'Schellens, Jan H.M.', 'Beijnen, Jos H.']",Biomark Insights,,,True
d5794d9e687b1087383f2bca0c5beaf31ebc2955,PMC,A Statistical Framework for the Adaptive Management of Epidemiological Interventions,http://dx.doi.org/10.1371/journal.pone.0005807,PMC2688756,19503812,CC BY,"BACKGROUND: Epidemiological interventions aim to control the spread of infectious disease through various mechanisms, each carrying a different associated cost. METHODOLOGY: We describe a flexible statistical framework for generating optimal epidemiological interventions that are designed to minimize the total expected cost of an emerging epidemic while simultaneously propagating uncertainty regarding the underlying disease model parameters through to the decision process. The strategies produced through this framework are adaptive: vaccination schedules are iteratively adjusted to reflect the anticipated trajectory of the epidemic given the current population state and updated parameter estimates. CONCLUSIONS: Using simulation studies based on a classic influenza outbreak, we demonstrate the advantages of adaptive interventions over non-adaptive ones, in terms of cost and resource efficiency, and robustness to model misspecification.",2009 Jun 5,"['Merl, Daniel', 'Johnson, Leah R.', 'Gramacy, Robert B.', 'Mangel, Marc']",PLoS One,,,True
7c0a15a70be63f9707358fb640e01b464e54dfd0,PMC,Strategies for successful recombinant expression of disulfide bond-dependent proteins in Escherichia coli,http://dx.doi.org/10.1186/1475-2859-8-26,PMC2689190,19442264,CC BY,"Bacteria are simple and cost effective hosts for producing recombinant proteins. However, their physiological features may limit their use for obtaining in native form proteins of some specific structural classes, such as for instance polypeptides that undergo extensive post-translational modifications. To some extent, also the production of proteins that depending on disulfide bridges for their stability has been considered difficult in E. coli. Both eukaryotic and prokaryotic organisms keep their cytoplasm reduced and, consequently, disulfide bond formation is impaired in this subcellular compartment. Disulfide bridges can stabilize protein structure and are often present in high abundance in secreted proteins. In eukaryotic cells such bonds are formed in the oxidizing environment of endoplasmic reticulum during the export process. Bacteria do not possess a similar specialized subcellular compartment, but they have both export systems and enzymatic activities aimed at the formation and at the quality control of disulfide bonds in the oxidizing periplasm. This article reviews the available strategies for exploiting the physiological mechanisms of bactera to produce properly folded disulfide-bonded proteins.",2009 May 14,"de Marco, Ario",Microb Cell Fact,,,True
3bd416cb6ace33b8879fa9e93778de31ae256773,PMC,What Is the Optimal Therapy for Patients with H5N1 Influenza?,http://dx.doi.org/10.1371/journal.pmed.1000091,PMC2694988,19554084,CC BY,"In a 2007 article in PLoS Medicine [10], Holger J. Schünemann and colleagues described a new process used by the World Health Organization for rapidly developing clinical management guidelines in emergency situations. These situations include outbreaks of emerging infectious diseases. The authors discussed how they developed such a “rapid advice” guideline for the pharmacological management of avian influenza A (H5N1) virus infection. The guideline recommends giving the antiviral drug oseltamivir at a dose of 75 mg twice daily for five days. In this Debate, Nicholas White argues that such dosing is inadequate, Robert Webster and Elena Govorkova say that combination antiviral therapy should be used, and Tim Uyeki reminds us that clinical care of patients with H5N1 entails much more than antiviral treatment. These issues may also apply to therapy of patients hospitalized with severe disease due to novel swine-origin influenza A (H1N1) virus infection.",2009 Jun 23,"['White, Nicholas J.', 'Webster, Robert G.', 'Govorkova, Elena A.', 'Uyeki, Timothy M.']",PLoS Med,,,True
5813a786b66940f45bd1083081448cc53edcadd4,PMC,Development of TaqMan(® )MGB fluorescent real-time PCR assay for the detection of anatid herpesvirus 1,http://dx.doi.org/10.1186/1743-422X-6-71,PMC2696427,19497115,CC BY,"BACKGROUND: Anatid herpesvirus 1 (AHV-1) is an alphaherpesvirus associated with latent infection and mortality in ducks and geese and is currently affecting the world-wide waterfowl production severely. Here we describe a fluorescent quantitative real-time PCR (FQ-PCR) method developed for fast measurement of AHV-1 DNA based on TaqMan MGB technology. RESULTS: The detection limit of the assay was 1 × 10(1 )standard DNA copies, with a sensitivity of 2 logs higher than that of the conventional gel-based PCR assay targeting the same gene. The real-time PCR was reproducible, as shown by satisfactory low intra-assay and inter-assay coefficients of variation. CONCLUSION: The high sensitivity, specificity, simplicity and reproducibility of the AHV-1 fluorogenic PCR assay, combined with its wide dynamic range and high throughput, make this method suitable for a broad spectrum of AHV-1 etiologically related application.",2009 Jun 4,"['Guo, Yufei', 'Cheng, Anchun', 'Wang, Mingshu', 'Shen, Chanjuan', 'Jia, Renyong', 'Chen, Shun', 'Zhang, Na']",Virol J,,,True
e3785336f334b853b3d269a8301dfc564f5fae74,PMC,Association of the shuffling of Streptococcus pyogenes clones and the fluctuation of scarlet fever cases between 2000 and 2006 in central Taiwan,http://dx.doi.org/10.1186/1471-2180-9-115,PMC2697166,19486515,CC BY,"BACKGROUND: The number of scarlet fever occurrences reported between 2000 and 2006 fluctuated considerably in central Taiwan and throughout the nation. Isolates of Streptococcus pyogenes were collected from scarlet fever patients in central Taiwan and were characterized by emm sequencing and a standardized pulsed-field gel electrophoresis (PFGE) method. National weekly report data were collected for investigating epidemiological trends. RESULTS: A total of 23 emm types were identified in 1,218 S. pyogenes isolates. The five most prevalent emm types were emm12 (50.4%), emm4 (23.2%), emm1 (16.4%), emm6 (3.8%) and emm22 (3.0%). PFGE analysis with SmaI suggested that, with a few exceptions, strains with a common emm type belonged to the same clone. There were two large emm12 clones, one with DNA resistant to cleavage by SmaI. Each prevalent emm clone had major PFGE strain(s) and many minor strains. Most of the minor strains emerged in the population and disappeared soon after. Even some major strains remained prevalent for only 2–3 years before declining. The large fluctuation of scarlet fever cases between 2000 and 2006 was associated with the shuffling of six prevalent emm clones. In 2003, the dramatic drop in scarlet fever cases in central Taiwan and throughout the whole country was associated with the occurrence of a severe acute respiratory syndrome (SARS) outbreak that occurred between late-February and mid-June in Taiwan. CONCLUSION: The occurrences of scarlet fever in central Taiwan in 2000–2006 were primarily caused by five emm types, which accounted for 96.8% of the isolates collected. Most of the S. pyogenes strains (as defined by PFGE genotypes) emerged and lasted for only a few years. The fluctuation in the number of scarlet fever cases during the seven years can be primarily attributed to the shuffling of six prevalent emm clones and to the SARS outbreak in 2003.",2009 Jun 1,"['Chiou, Chien-Shun', 'Wang, You-Wun', 'Chen, Pei-Ling', 'Wang, Wan-Ling', 'Wu, Ping-Fuai', 'Wei, Hsiao-Lun']",BMC Microbiol,,,True
17d6161faae981aa6c56ac58d9c1d30ed581b05f,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,True
f1b4911a5d641bccc19aec9b8b2cd02e1f0e11dd,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,False
5e85e7bcf8d9f02e744c9fba06e78a2653a0e238,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,False
9861f6865482d2353d77c8695eef0079539feeb0,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,False
b79bd179bc542b31f7c76f7115c5a338dfa3c614,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,False
97fa68ad1301de1773b18140530ef974ba6262a2,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,False
ab5841bc722a51ed45cff24f1d419916b3a83427,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,False
251158df2bf3b5bb57e84ff466737b9917df0fd1,PMC,IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico,http://dx.doi.org/10.1186/1471-2105-10-160,PMC2698906,19473520,CC BY,"BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.",2009 May 27,"['Wu, Tzong-Yuan', 'Hsieh, Chi-Chun', 'Hong, Jun-Jie', 'Chen, Chung-Yung', 'Tsai, Yuh-Show']",BMC Bioinformatics,,,False
bad87b7effc9c6f6a9ef4ca024f7fe86daff4f45,PMC,Emerging trends in plasma-free manufacturing of recombinant protein therapeutics expressed in mammalian cells,http://dx.doi.org/10.1002/biot.200800241,PMC2699044,19226552,CC BY,"Mammalian cells are the expression system of choice for therapeutic proteins, especially those requiring complex post-translational modifications. Traditionally, these cells are grown in medium supplemented with serum and other animal-or human-derived components to support viability and productivity. Such proteins are also typically added as excipients and stabilizers in the final drug formulation. However, the transmission of hepatitis B in the 1970s and of hepatitis C and HIV in the 1980s through plasma-derived factor VIII concentrates had catastrophic consequences for hemophilia patients. Thus, due to regulatory concerns about the inherent potential for transmission of infectious agents as well as the heterogeneity and lack of reliability of the serum supply, a trend has emerged to eliminate the use of plasma-derived additives in the production and formulation of recombinant protein therapeutics. This practice began with products used in the treatment of hemophilia and is progressively expanding throughout the entire industry. The plasma-free method of producing recombinant therapeutics is accomplished by the use of both cell culture media and final product formulations that do not contain animal-or human-derived additives. A number of recombinant therapeutic proteins for the treatment of several different diseases have been produced by plasma-free processes, with the objective of improving safety by eliminating blood-borne pathogens or by reducing immunogenicity. This review describes the factors that drove the development of plasma-free protein therapeutics and provides examples of advances in manufacturing that have made possible the removal of human and animal-derived products from all steps of recombinant protein production.",2009 Feb,"['Grillberger, Leopold', 'Kreil, Thomas R', 'Nasr, Sonia', 'Reiter, Manfred']",Biotechnol J,,,True
c7b16abf574515b631f758dc51170ef757fd58b4,PMC,Lactate Dehydrogenase-Elevating Virus Induces Systemic Lymphocyte Activation via TLR7-Dependent IFNα Responses by Plasmacytoid Dendritic Cells,http://dx.doi.org/10.1371/journal.pone.0006105,PMC2699471,19568424,CC0,"BACKGROUND: Lactate dehydrogenase-elevating virus (LDV) is a natural infectious agent of mice. Like several other viruses, LDV causes widespread and very rapid but transient activation of both B cells and T cells in lymphoid tissues and the blood. The mechanism of this activation has not been fully described and is the focus of the current studies. PRINCIPAL FINDINGS: A known inducer of early lymphocyte activation is IFNα, a cytokine strongly induced by LDV infection. Neutralization of IFNα in the plasma from infected mice ablated its ability to activate lymphocytes in vitro. Since the primary source of virus-induced IFNα in vivo is often plasmacytoid dendritic cells (pDC's), we depleted these cells prior to LDV infection and tested for lymphocyte activation. Depletion of pDC's in vivo eradicated both the LDV-induced IFNα response and lymphocyte activation. A primary receptor in pDC's for single stranded RNA viruses such as LDV is the toll-like receptor 7 (TLR7) pattern recognition receptor. Infection of TLR7-knockout mice revealed that both the IFNα response and lymphocyte activation were dependent on TLR7 signaling in vivo. Interestingly, virus levels in both TLR7 knockout mice and pDC-depleted mice were indistinguishable from controls indicating that LDV is largely resistant to the systemic IFNα response. CONCLUSION: Results indicate that LDV-induced activation of lymphocytes is due to recognition of LDV nucleic acid by TLR7 pattern recognition receptors in pDC's that respond with a lymphocyte-inducing IFNα response.",2009 Jul 1,"['Ammann, Christoph G.', 'Messer, Ronald J.', 'Peterson, Karin E.', 'Hasenkrug, Kim J.']",PLoS One,,,True
6f048749badc8f1c756857ceb24421f5e6c05e62,PMC,Patterns of perception toward influenza pandemic among the front-line responsible health personnel in southern Thailand: a Q methodology approach,http://dx.doi.org/10.1186/1471-2458-9-161,PMC2700101,19473550,CC BY,"BACKGROUND: Thailand has joined the World Health Organization effort to prepare against a threat of an influenza pandemic. Regular monitoring on preparedness of health facilities and assessment on perception of the front-line responsible health personnel has never been done. This study aimed to document the patterns of perception of health personnel toward the threat of an influenza pandemic. METHODS: Q methodology was applied to a set of 385 health personnel in charge of influenza pandemic preparedness in the three southernmost provinces of Thailand. Subjects were asked to rank 33 statements about various issues of influenza pandemic according to a pre-designed score sheet having a quasi-normal distribution on a continuous 9-point bipolar scale ranging from -4 for strongly disagree to +4 for strongly agree. The Q factor analysis method was employed to identify patterns based on the similarity and dissimilarity among health personnel. RESULTS: There were three main patterns of perception toward influenza pandemic with moderate correlation coefficients between patterns ranging from 0.37 to 0.55. Pattern I, health personnel, which we labeled pessimistic, perceived themselves as having a low self-efficacy. Pattern II, which we labeled optimistic, perceived the threat to be low severity and low vulnerability. Pattern III, which we labeled mixed, perceived low self-efficacy but low vulnerability. Across the three patterns, almost all the subjects had a high expectancy that execution of recommended measures can mitigate impacts of the threat of an influenza pandemic, particularly on multi-measures with high factor scores of 4 in all patterns. The most conflicting area was vulnerability on the possible impacts of an influenza pandemic, having factor scores of high (3), low (-4), and neutral (0) for patterns I, II, and III, respectively. CONCLUSION: Strong consistent perceptions of response efficacy against an influenza pandemic may suggest a low priority to convince health personnel on the efficacy of the recommended measures. Lack of self-efficacy in certain sub-groups indicates the need for program managers to improve self-confidence of health personnel to participate in an emergency response.",2009 May 28,"['Prateepko, Tapanan', 'Chongsuvivatwong, Virasakdi']",BMC Public Health,,,True
b7bd823d7175ee551d3ba8508e5457d650056fd6,PMC,Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells,http://dx.doi.org/10.1371/journal.pone.0006130,PMC2700284,19572016,CC BY,"Coronavirus host and cell specificities are determined by specific interactions between the viral spike (S) protein and host cell receptor(s). Avian coronavirus infectious bronchitis (IBV) has been adapted to embryonated chicken eggs, primary chicken kidney (CK) cells, monkey kidney cell line Vero, and other human and animal cells. Here we report that acquisition of the cell–cell fusion activity by amino acid mutations in the S protein determines the infectivity of IBV in cultured cells. Expression of S protein derived from Vero- and CK-adapted strains showed efficient induction of membrane fusion. However, expression of S protein cloned from the third passage of IBV in chicken embryo (EP3) did not show apparent syncytia formation. By construction of chimeric S constructs and site-directed mutagenesis, a point mutation (L857-F) at amino acid position 857 in the heptad repeat 1 region of S protein was shown to be responsible for its acquisition of the cell–cell fusion activity. Furthermore, a G405-D point mutation in the S1 domain, which was acquired during further propagation of Vero-adapted IBV in Vero cells, could enhance the cell–cell fusion activity of the protein. Re-introduction of L857 back to the S gene of Vero-adapted IBV allowed recovery of variants that contain the introduced L857. However, compensatory mutations in S1 and some distant regions of S2 were required for restoration of the cell–cell fusion activity of S protein carrying L857 and for the infectivity of the recovered variants in cultured cells. This study demonstrates that acquisition of the cell–cell fusion activity in S protein determines the selection and/or adaptation of a coronavirus from chicken embryo to cultured cells of human and animal origins.",2009 Jul 2,"['Yamada, Yoshiyuki', 'Liu, Xiao Bo', 'Fang, Shou Guo', 'Tay, Felicia P. L.', 'Liu, Ding Xiang']",PLoS One,,,True
a600310d78ebe675d0d7bc5d9188a77d73e0e79a,PMC,"Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells",http://dx.doi.org/10.1186/1471-2172-10-35,PMC2700820,19505311,CC BY,"BACKGROUND: The SARS outbreak in 2003 provides a unique opportunity for the study of human responses to a novel virus. We have previously reported that dendritic cells (DCs) might be involved in the immune escape mechanisms for SARS-CoV. In this study, we focussed on the gene expression of toll-like receptors (TLRs), chemokine receptors (CCRs) and death receptor ligands in SARS-CoV infected DCs. We also compared adult and cord blood (CB) DCs to find a possible explanation for the age-dependent severity of SARS. RESULTS: Our results demonstrates that SARS-CoV did not modulate TLR-1 to TLR-10 gene expression but significantly induced the expression of CCR-1, CCR-3, and CCR-5. There was also strong induction of TNF-related apoptosis-inducing ligand (TRAIL), but not Fas ligand gene expression in SARS-CoV infected DCs. Interestingly, the expressions of most genes studied were higher in CB DCs than adult DCs. CONCLUSION: The upregulation of chemokines and CCRs may facilitate DC migration from the infection site to the lymph nodes, whereas the increase of TRAIL may induce lymphocyte apoptosis. These findings may explain the increased lung infiltrations and lymphoid depletion in SARS patients. Further explorations of the biological significance of these findings are warranted.",2009 Jun 8,"['Law, Helen KW', 'Cheung, Chung Yan', 'Sia, Sin Fun', 'Chan, Yuk On', 'Peiris, JS Malik', 'Lau, Yu Lung']",BMC Immunol,,,True
3576b9e0d1895a2d2cb0231304425e1633e86e82,PMC,The Y271 and I274 Amino Acids in Reverse Transcriptase of Human Immunodeficiency Virus-1 Are Critical to Protein Stability,http://dx.doi.org/10.1371/journal.pone.0006108,PMC2701634,19578544,CC BY,"Reverse transcriptase (RT) of human immunodeficiency virus (HIV)-1 plays a key role in initiating viral replication and is an important target for developing anti-HIV drugs. Our previous study showed that two mutations (Y271A and I274A) in the turn RT (Gln(269)-Arg(277)) abrogated viral replication, but the replication capacity and RT activity was discordant. In this study, we further investigated why alanine substitutions at these two sites would affect viral replication. We found that both RT activity and RT protein were almost undetectable in viral particles of these two mutants, although the Pr160(gag-pol) mutants were properly expressed, transported and incorporated. Using protease inhibition assay, we demonstrated a correlation between the degradation of the RT mutants and the activity of viral protease. Our native gel analysis indicated that the mutations at 271 and 274 amino acids might cause conformational changes, leading to the formation of higher order oligomers instead of dimers, resulting in increased protein instability and susceptibility to viral protease. Thus, residues 271 and 274 are critical to RT stability and resistance to viral protease. The conservation of the two amino acid residues among different strains of HIV-1 lent further support to this conclusion. The knowledge gained here may prove useful in drug design.",2009 Jul 3,"['Zhang, Hao-Jie', 'Wang, Yong-Xiang', 'Wu, Hao', 'Jin, Dong-Yan', 'Wen, Yu-Mei', 'Zheng, Bo-Jian']",PLoS One,,,True
d09827278115fad7feb41c47b6da245f54ba1453,PMC,Structure and Inhibition of the SARS Coronavirus Envelope Protein Ion Channel,http://dx.doi.org/10.1371/journal.ppat.1000511,PMC2702000,19593379,CC BY,"The envelope (E) protein from coronaviruses is a small polypeptide that contains at least one α-helical transmembrane domain. Absence, or inactivation, of E protein results in attenuated viruses, due to alterations in either virion morphology or tropism. Apart from its morphogenetic properties, protein E has been reported to have membrane permeabilizing activity. Further, the drug hexamethylene amiloride (HMA), but not amiloride, inhibited in vitro ion channel activity of some synthetic coronavirus E proteins, and also viral replication. We have previously shown for the coronavirus species responsible for severe acute respiratory syndrome (SARS-CoV) that the transmembrane domain of E protein (ETM) forms pentameric α-helical bundles that are likely responsible for the observed channel activity. Herein, using solution NMR in dodecylphosphatidylcholine micelles and energy minimization, we have obtained a model of this channel which features regular α-helices that form a pentameric left-handed parallel bundle. The drug HMA was found to bind inside the lumen of the channel, at both the C-terminal and the N-terminal openings, and, in contrast to amiloride, induced additional chemical shifts in ETM. Full length SARS-CoV E displayed channel activity when transiently expressed in human embryonic kidney 293 (HEK-293) cells in a whole-cell patch clamp set-up. This activity was significantly reduced by hexamethylene amiloride (HMA), but not by amiloride. The channel structure presented herein provides a possible rationale for inhibition, and a platform for future structure-based drug design of this potential pharmacological target.",2009 Jul 10,"['Pervushin, Konstantin', 'Tan, Edward', 'Parthasarathy, Krupakar', 'Lin, Xin', 'Jiang, Feng Li', 'Yu, Dejie', 'Vararattanavech, Ardcharaporn', 'Soong, Tuck Wah', 'Liu, Ding Xiang', 'Torres, Jaume']",PLoS Pathog,,,True
610adc2e0b9fea5bdaa4ea21b46e4bd6b02d558d,PMC,Structure and Inhibition of the SARS Coronavirus Envelope Protein Ion Channel,http://dx.doi.org/10.1371/journal.ppat.1000511,PMC2702000,19593379,CC BY,"The envelope (E) protein from coronaviruses is a small polypeptide that contains at least one α-helical transmembrane domain. Absence, or inactivation, of E protein results in attenuated viruses, due to alterations in either virion morphology or tropism. Apart from its morphogenetic properties, protein E has been reported to have membrane permeabilizing activity. Further, the drug hexamethylene amiloride (HMA), but not amiloride, inhibited in vitro ion channel activity of some synthetic coronavirus E proteins, and also viral replication. We have previously shown for the coronavirus species responsible for severe acute respiratory syndrome (SARS-CoV) that the transmembrane domain of E protein (ETM) forms pentameric α-helical bundles that are likely responsible for the observed channel activity. Herein, using solution NMR in dodecylphosphatidylcholine micelles and energy minimization, we have obtained a model of this channel which features regular α-helices that form a pentameric left-handed parallel bundle. The drug HMA was found to bind inside the lumen of the channel, at both the C-terminal and the N-terminal openings, and, in contrast to amiloride, induced additional chemical shifts in ETM. Full length SARS-CoV E displayed channel activity when transiently expressed in human embryonic kidney 293 (HEK-293) cells in a whole-cell patch clamp set-up. This activity was significantly reduced by hexamethylene amiloride (HMA), but not by amiloride. The channel structure presented herein provides a possible rationale for inhibition, and a platform for future structure-based drug design of this potential pharmacological target.",2009 Jul 10,"['Pervushin, Konstantin', 'Tan, Edward', 'Parthasarathy, Krupakar', 'Lin, Xin', 'Jiang, Feng Li', 'Yu, Dejie', 'Vararattanavech, Ardcharaporn', 'Soong, Tuck Wah', 'Liu, Ding Xiang', 'Torres, Jaume']",PLoS Pathog,,,True
9ad61dcfb0a71ebe88c497995cf569eba5e73f8c,PMC,"Enhancement of the expression of HCV core gene does not enhance core-specific immune response in DNA immunization: advantages of the heterologous DNA prime, protein boost immunization regimen",http://dx.doi.org/10.1186/1479-0556-7-7,PMC2702340,19505299,CC BY,"BACKGROUND: Hepatitis C core protein is an attractive target for HCV vaccine aimed to exterminate HCV infected cells. However, although highly immunogenic in natural infection, core appears to have low immunogenicity in experimental settings. We aimed to design an HCV vaccine prototype based on core, and devise immunization regimens that would lead to potent anti-core immune responses which circumvent the immunogenicity limitations earlier observed. METHODS: Plasmids encoding core with no translation initiation signal (pCMVcore); with Kozak sequence (pCMVcoreKozak); and with HCV IRES (pCMVcoreIRES) were designed and expressed in a variety of eukaryotic cells. Polyproteins corresponding to HCV 1b amino acids (aa) 1–98 and 1–173 were expressed in E. coli. C57BL/6 mice were immunized with four 25-μg doses of pCMVcoreKozak, or pCMV (I). BALB/c mice were immunized with 100 μg of either pCMVcore, or pCMVcoreKozak, or pCMVcoreIRES, or empty pCMV (II). Lastly, BALB/c mice were immunized with 20 μg of core aa 1–98 in prime and boost, or with 100 μg of pCMVcoreKozak in prime and 20 μg of core aa 1–98 in boost (III). Antibody response, [(3)H]-T-incorporation, and cytokine secretion by core/core peptide-stimulated splenocytes were assessed after each immunization. RESULTS: Plasmids differed in core-expression capacity: mouse fibroblasts transfected with pCMVcore, pCMVcoreIRES and pCMVcoreKozak expressed 0.22 ± 0.18, 0.83 ± 0.5, and 13 ± 5 ng core per cell, respectively. Single immunization with highly expressing pCMVcoreKozak induced specific IFN-γ and IL-2, and weak antibody response. Single immunization with plasmids directing low levels of core expression induced similar levels of cytokines, strong T-cell proliferation (pCMVcoreIRES), and antibodies in titer 10(3)(pCMVcore). Boosting with pCMVcoreKozak induced low antibody response, core-specific T-cell proliferation and IFN-γ secretion that subsided after the 3rd plasmid injection. The latter also led to a decrease in specific IL-2 secretion. The best was the heterologous pCMVcoreKozak prime/protein boost regimen that generated mixed Th1/Th2-cellular response with core-specific antibodies in titer ≥ 3 × 10(3). CONCLUSION: Thus, administration of highly expressed HCV core gene, as one large dose or repeated injections of smaller doses, may suppress core-specific immune response. Instead, the latter is induced by a heterologous DNA prime/protein boost regimen that circumvents the negative effects of intracellular core expression.",2009 Jun 8,"['Alekseeva, Ekaterina', 'Sominskaya, Irina', 'Skrastina, Dace', 'Egorova, Irina', 'Starodubova, Elizaveta', 'Kushners, Eriks', 'Mihailova, Marija', 'Petrakova, Natalia', 'Bruvere, Ruta', 'Kozlovskaya, Tatyana', 'Isaguliants, Maria', 'Pumpens, Paul']",Genet Vaccines Ther,,,True
323e747a1a351a6ec4053512e45718fc27d242d3,PMC,The impact on neonatal mortality of shifting childbirth services among levels of hospitals: Taiwan's experience,http://dx.doi.org/10.1186/1472-6963-9-94,PMC2703635,19505330,CC BY,"BACKGROUND: There is considerable discussion surrounding whether advanced hospitals provide better childbirth care than local community hospitals. This study examines the effect of shifting childbirth services from advanced hospitals (i.e., medical centers and regional hospitals) to local community hospitals (i.e., clinics and district hospitals). The sample population was tracked over a seven-year period, which includes the four months of the 2003 severe acute respiratory syndrome (SARS) epidemic in Taiwan. During the SARS epidemic, pregnant women avoided using maternity services in advanced hospitals. Concerns have been raised about maintaining the quality of maternity care with increased demands on childbirth services in local community hospitals. In this study, we analyzed the impact of shifting maternity services among hospitals of different levels on neonatal mortality and maternal deaths. METHODS: A population-based study was conducted using data from Taiwan's National Health Insurance annual statistics of monthly county neonatal morality rates. Based on a pre-SARS sample from January 1998 to December 2002, we estimated a linear regression model which included ""trend,"" a continuous variable representing the effect of yearly changes, and two binary variables, ""month"" and ""county,"" controlling for seasonal and county-specific effects. With the estimated coefficients, we obtained predicted neonatal mortality rates for each county-month. We compared the differences between observed mortality rates of the SARS period and predicted rates to examine whether the shifting in maternity services during the SARS epidemic significantly affected neonatal mortality rates. RESULTS: With an analysis of a total of 1,848 observations between 1998 and 2004, an insignificantly negative mean of standardized predicted errors during the SARS period was found. The result of a sub-sample containing areas with advanced hospitals showed a significant negative mean of standardized predicted errors during the SARS period. These findings indicate that despite increased use of local community hospitals, neonatal mortality during the SARS epidemic did not increase, and even decreased in areas with advanced hospitals. CONCLUSION: An increased use of maternity services in local community hospitals occurred during the SARS epidemic in Taiwan. However, we observed no increase in neonatal and maternity mortality associated with these increased demands on local community hospitals.",2009 Jun 8,"['Wang, Shi-Yi', 'Hsu, Sylvia H', 'Chen, Li-Kuei']",BMC Health Serv Res,,,True
eb49cb90e8f1868b1d73beef301de0ebc481f183,PMC,High-titer preparation of Bombyx mori nucleopolyhedrovirus (BmNPV) displaying recombinant protein in silkworm larvae by size exclusion chromatography and its characterization,http://dx.doi.org/10.1186/1472-6750-9-55,PMC2703641,19523201,CC BY,"BACKGROUND: Budded baculoviruses are utilized for vaccine, the production of antibody and functional analysis of transmembrane proteins. In this study, we tried to produce and purify the recombinant Bombyx mori nucleopolyhedrovirus (rBmNPV-hPRR) that displayed human (pro)renin receptor (hPRR) connected with FLAG peptide sequence on its own surface. These particles were used for further binding analysis of hPRR to human prorenin. The rBmNPV-hPRR was produced in silkworm larvae and purified from its hemolymph using size exclusion chromatography (SEC). RESULTS: A rapid method of BmNPV titer determination in hemolymph was performed using quantitative real-time PCR (Q-PCR). A correlation coefficient of BmNPV determination between end-point dilution and Q-PCR methods was found to be 0.99. rBmNPV-hPRR bacmid-injected silkworm larvae produced recombinant baculovirus of 1.31 × 10(8 )plaque forming unit (pfu) in hemolymph, which was 2.8 × 10(4 )times higher than transfection solution in Bm5 cells. Its purification yield by Sephacryl S-1000 SF column chromatography was 264 fold from larval hemolymph at 4 days post-injection (p.i.), but 35 or 39 fold at 4.5 or 5 days p.i., respectively. Protein patterns of rBmNPV-hPRR purified at 4 and 5 days were the same and ratio of envelope proteins (76, 45 and 35 kDa) to VP39, one of nucleocapsid proteins, increased at 5 days p.i. hPRR was detected in only purified rBmNPV-hPRR at 5 days p.i.. CONCLUSION: The successful purification of rBmNPV-hPRR indicates that baculovirus production using silkworm larvae and its purification from hemolymph by Sephacryl S-1000 SF column chromatography can provide an economical approach in obtaining the purified BmNPV stocks with high titer for large-scale production of hPRR. Also, it can be utilized for further binding analysis and screening of inhibitors of hPRR.",2009 Jun 12,"['Kato, Tatsuya', 'Manoha, Suganthi Lavender', 'Tanaka, Shigeyasu', 'Park, Enoch Y']",BMC Biotechnol,,,True
76dae8b8fd43335310edca09c522640ac9027edf,PMC,Crystal Structure of the C-Terminal Cytoplasmic Domain of Non-Structural Protein 4 from Mouse Hepatitis Virus A59,http://dx.doi.org/10.1371/journal.pone.0006217,PMC2703826,19593433,CC BY,"BACKGROUND: The replication of coronaviruses takes place on cytoplasmic double membrane vesicles (DMVs) originating in the endoplasmic reticulum (ER). Three trans-membrane non-structural proteins, nsp3, nsp4 and nsp6, are understood to be membrane anchors of the coronavirus replication complex. Nsp4 is localized to the ER membrane when expressed alone but is recruited into the replication complex in infected cells. It is revealed to contain four trans-membrane regions and its N- and C-termini are exposed to the cytosol. METHODOLOGY/PRINCIPAL FINDINGS: We have determined the crystal structures of the C-terminal hydrophilic domain of nsp4 (nsp4C) from MHV strain A59 and a C425S site-directed mutant. The highly conserved 89 amino acid region from T408 to Q496 is shown to possess a new fold. The wild-type (WT) structure features two monomers linked by a Cys425-Cys425 disulfide bond in one asymmetric unit. The monomers are arranged with their N- and C-termini in opposite orientations to form an “open” conformation. Mutation of Cys425 to Ser did not affect the monomer structure, although the mutant dimer adopts strikingly different conformations by crystal packing, with the cross-linked C-termini and parallel N-termini of two monomers forming a “closed” conformation. The WT nsp4C exists as a dimer in solution and can dissociate easily into monomers in a reducing environment. CONCLUSIONS/SIGNIFICANCE: As nsp4C is exposed in the reducing cytosol, the monomer of nsp4C should be physiological. This structure may serve as a basis for further functional studies of nsp4.",2009 Jul 10,"['Xu, Xiaoling', 'Lou, Zhiyong', 'Ma, Yanlin', 'Chen, Xuehui', 'Yang, Zhangsheng', 'Tong, Xiaohang', 'Zhao, Qi', 'Xu, Yuanyuan', 'Deng, Hongyu', 'Bartlam, Mark', 'Rao, Zihe']",PLoS One,,,True
a6761d94a9d2827b88e04a42b2e2ddd8036ba410,PMC,CFTR Delivery to 25% of Surface Epithelial Cells Restores Normal Rates of Mucus Transport to Human Cystic Fibrosis Airway Epithelium,http://dx.doi.org/10.1371/journal.pbio.1000155,PMC2705187,19621064,CC0,"Dysfunction of CFTR in cystic fibrosis (CF) airway epithelium perturbs the normal regulation of ion transport, leading to a reduced volume of airway surface liquid (ASL), mucus dehydration, decreased mucus transport, and mucus plugging of the airways. CFTR is normally expressed in ciliated epithelial cells of the surface and submucosal gland ductal epithelium and submucosal gland acinar cells. Critical questions for the development of gene transfer strategies for CF airway disease are what airway regions require CFTR function and how many epithelial cells require CFTR expression to restore normal ASL volume regulation and mucus transport to CF airway epithelium? An in vitro model of human CF ciliated surface airway epithelium (CF HAE) was used to test whether a human parainfluenza virus (PIV) vector engineered to express CFTR (PIVCFTR) could deliver sufficient CFTR to CF HAE to restore mucus transport, thus correcting the CF phenotype. PIVCFTR delivered CFTR to >60% of airway surface epithelial cells and expressed CFTR protein in CF HAE approximately 100-fold over endogenous levels in non-CF HAE. This efficiency of CFTR delivery fully corrected the basic bioelectric defects of Cl(−) and Na(+) epithelial ion transport and restored ASL volume regulation and mucus transport to levels approaching those of non-CF HAE. To determine the numbers of CF HAE surface epithelial cells required to express CFTR for restoration of mucus transport to normal levels, different amounts of PIVCFTR were used to express CFTR in 3%–65% of the surface epithelial cells of CF HAE and correlated to increasing ASL volumes and mucus transport rates. These data demonstrate for the first time, to our knowledge, that restoration of normal mucus transport rates in CF HAE was achieved after CFTR delivery to 25% of surface epithelial cells. In vivo experimentation in appropriate models will be required to determine what level of mucus transport will afford clinical benefit to CF patients, but we predict that a future goal for corrective gene transfer to the CF human airways in vivo would attempt to target at least 25% of surface epithelial cells to achieve mucus transport rates comparable to those in non-CF airways.",2009 Jul 21,"['Zhang, Liqun', 'Button, Brian', 'Gabriel, Sherif E.', 'Burkett, Susan', 'Yan, Yu', 'Skiadopoulos, Mario H.', 'Dang, Yan Li', 'Vogel, Leatrice N.', 'McKay, Tristan', 'Mengos, April', 'Boucher, Richard C.', 'Collins, Peter L.', 'Pickles, Raymond J.']",PLoS Biol,,,True
f4016789973bc61cdb84c457c95e15426e2143b3,PMC,"Occurrence of HSV-1-induced pneumonitis in patients under standard immunosuppressive therapy for rheumatic, vasculitic, and connective tissue disease",http://dx.doi.org/10.1186/1471-2466-9-22,PMC2705343,19450259,CC BY,"BACKGROUND: Herpes simplex virus type-1 (HSV-1) has been described to cause respiratory tract infections in critically ill patients or in individuals that are immunocompromised. It is a continuing matter of debate under which circumstances HSV-1 is a relevant pathogen for pneumonitis. While its role during critical illness has been investigated by prospective interventional studies, comparatively little systematic data is available on the role of HSV-1 for pneumonitis in outpatients with autoimmune disease under a maintenance regimen of immunosuppression. METHODS: We retrospectively reviewed the charts of ~1400 patients with rheumatoid arthritis, vasculitis, and systemic lupus erythematosus (SLE) that were followed at the outpatient clinic of a German University hospital during the years 2000–2007. Episodes of admission to a ward resulting in the diagnosis of pneumonia/pneumonitis were identified, and the type of pneumonia and clinical features retrospectively studied. RESULTS: 63 patients with rheumatoid arthritis, vasculitis, or SLE were admitted to a ward and diagnosed to have pneumonia/pneumonitis. Using bronchoscopy a total of 6 cases of pulmonary infection associated with HSV-1 in the lower respiratory tract were identified. Among those, 2 cases suggested a causative role of HSV-1 as the sole agent causing pneumonitis that proved clinically responsive to antiviral treatment. In the remaining 4 cases HSV-1 appeared as a bystander of bacterial infection. Maintenance therapy with leflunomide, which inhibits HSV-1 assembly in vitro, was associated with a milder course of pneumonitis in one patient. Detection of HSV-1 was associated with stronger immunosuppressive regimens and vasculitic disease. CONCLUSION: The present study analyzed the frequency and hallmarks of cases of HSV-1 associated pneumonitis that occurred in a comparatively large cohort of patients with rheumatologic autoimmune diseases. In an area of controversy, this study provides further evidence that HSV-1 causes isolated pneumonitis in the immunocompromised. The study may provide an estimate on the frequency of relevant HSV-1 infection and bacterial agents in outpatients with autoimmune disease.",2009 May 18,"['Witt, Matthias N', 'Braun, Gerald S', 'Ihrler, Stephan', 'Schmid, Holger']",BMC Pulm Med,,,True
4395141eef1089f1c75a14912fade412fd694c19,PMC,"Studies on membrane topology, N-glycosylation and functionality of SARS-CoV membrane protein",http://dx.doi.org/10.1186/1743-422X-6-79,PMC2705359,19534833,CC BY,"The glycosylated membrane protein M of the severe acute respiratory syndrome associated coronavirus (SARS-CoV) is the main structural component of the virion and mediates assembly and budding of viral particles. The membrane topology of SARS-CoV M and the functional significance of its N-glycosylation are not completely understood as is its interaction with the surface glycoprotein S. Using biochemical and immunofluorescence analyses we found that M consists of a short glycosylated N-terminal ectodomain, three transmembrane segments and a long, immunogenic C-terminal endodomain. Although the N-glycosylation site of M seems to be highly conserved between group 1 and 3 coronaviruses, studies using a recombinant SARS-CoV expressing a glycosylation-deficient M revealed that N-glycosylation of M neither influence the shape of the virions nor their infectivity in cell culture. Further functional analysis of truncated M proteins showed that the N-terminal 134 amino acids comprising the three transmembrane domains are sufficient to mediate accumulation of M in the Golgi complex and to enforce recruitment of the viral spike protein S to the sites of virus assembly and budding in the ERGIC.",2009 Jun 18,"['Voß, Daniel', 'Pfefferle, Susanne', 'Drosten, Christian', 'Stevermann, Lea', 'Traggiai, Elisabetta', 'Lanzavecchia, Antonio', 'Becker, Stephan']",Virol J,,,True
9becd2019e0ff5052d47d3d23201cc521375cb03,PMC,Toward unsupervised outbreak detection through visual perception of new patterns,http://dx.doi.org/10.1186/1471-2458-9-179,PMC2706246,19515246,CC BY,"BACKGROUND: Statistical algorithms are routinely used to detect outbreaks of well-defined syndromes, such as influenza-like illness. These methods cannot be applied to the detection of emerging diseases for which no preexisting information is available. This paper presents a method aimed at facilitating the detection of outbreaks, when there is no a priori knowledge of the clinical presentation of cases. METHODS: The method uses a visual representation of the symptoms and diseases coded during a patient consultation according to the International Classification of Primary Care 2(nd )version (ICPC-2). The surveillance data are transformed into color-coded cells, ranging from white to red, reflecting the increasing frequency of observed signs. They are placed in a graphic reference frame mimicking body anatomy. Simple visual observation of color-change patterns over time, concerning a single code or a combination of codes, enables detection in the setting of interest. RESULTS: The method is demonstrated through retrospective analyses of two data sets: description of the patients referred to the hospital by their general practitioners (GPs) participating in the French Sentinel Network and description of patients directly consulting at a hospital emergency department (HED). Informative image color-change alert patterns emerged in both cases: the health consequences of the August 2003 heat wave were visualized with GPs' data (but passed unnoticed with conventional surveillance systems), and the flu epidemics, which are routinely detected by standard statistical techniques, were recognized visually with HED data. CONCLUSION: Using human visual pattern-recognition capacities to detect the onset of unexpected health events implies a convenient image representation of epidemiological surveillance and well-trained ""epidemiology watchers"". Once these two conditions are met, one could imagine that the epidemiology watchers could signal epidemiological alerts, based on ""image walls"" presenting the local, regional and/or national surveillance patterns, with specialized field epidemiologists assigned to validate the signals detected.",2009 Jun 10,"['Lévy, Pierre P', 'Valleron, Alain-Jacques']",BMC Public Health,,,True
049294a884d39102b06a634ba0f4bd3185fcc478,PMC,"Klassevirus 1, a previously undescribed member of the family Picornaviridae, is globally widespread",http://dx.doi.org/10.1186/1743-422X-6-86,PMC2706813,19552824,CC BY,"BACKGROUND: Diarrhea is the third leading infectious cause of death worldwide and is estimated to be responsible for approximately 2 million deaths a year. While many infectious causes of diarrhea have been established, approximately 40% of all diarrhea cases are of unknown etiology. In an effort to identify novel viruses that may be causal agents of diarrhea, we used high throughput mass sequencing to analyze stool samples collected from patients with acute diarrhea. RESULTS: Sequences with limited similarity to known picornaviruses were detected in a stool sample collected in Australia from a child with acute diarrhea. Using a combination of mass sequencing, RT-PCR, 5' RACE and 3' RACE, a 6383 bp fragment of the viral genome was sequenced. Phylogenetic analysis demonstrated that this virus was highly divergent from, but most closely related to, members of the genus Kobuvirus. We have tentatively named this novel virus klassevirus 1. We also detected klassevirus 1 by RT-PCR in a diarrhea specimen collected from a patient in St. Louis, United States as well as in untreated sewage collected in Barcelona, Spain. CONCLUSION: Klassevirus 1 is a previously undescribed picornavirus that is globally widespread and present on at least three continents. Further investigations to determine whether klassevirus 1 is a human pathogen are needed.",2009 Jun 24,"['Holtz, Lori R', 'Finkbeiner, Stacy R', 'Zhao, Guoyan', 'Kirkwood, Carl D', 'Girones, Rosina', 'Pipas, James M', 'Wang, David']",Virol J,,,True
63205fe99a388f19fde06f422c9ce6c1ddfc52f4,PMC,"Remission of Invasive, Cancer Stem-Like Glioblastoma Xenografts Using Lentiviral Vector-Mediated Suicide Gene Therapy",http://dx.doi.org/10.1371/journal.pone.0006314,PMC2707627,19617915,CC BY,"BACKGROUND: Glioblastoma is the most frequent and most malignant primary brain tumor with a poor prognosis. The translation of therapeutic strategies for glioblastoma from the experimental phase into the clinic has been limited by insufficient animal models, which lack important features of human tumors. Lentiviral gene therapy is an attractive therapeutic option for human glioblastoma, which we validated in a clinically relevant animal model. METHODOLOGY/PRINCIPAL FINDINGS: We used a rodent xenograft model that recapitulates the invasive and angiogenic features of human glioblastoma to analyze the transduction pattern and therapeutic efficacy of lentiviral pseudotyped vectors. Both, lymphocytic choriomeningitis virus glycoprotein (LCMV-GP) and vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentiviral vectors very efficiently transduced human glioblastoma cells in vitro and in vivo. In contrast, pseudotyped gammaretroviral vectors, similar to those evaluated for clinical therapy of glioblastoma, showed inefficient gene transfer in vitro and in vivo. Both pseudotyped lentiviral vectors transduced cancer stem-like cells characterized by their CD133-, nestin- and SOX2-expression, the ability to form spheroids in neural stem cell medium and to express astrocytic and neuronal differentiation markers under serum conditions. In a therapeutic approach using the suicide gene herpes simplex virus thymidine kinase (HSV-1-tk) fused to eGFP, both lentiviral vectors mediated a complete remission of solid tumors as seen on MRI resulting in a highly significant survival benefit (p<0.001) compared to control groups. In all recurrent tumors, surviving eGFP-positive tumor cells were found, advocating prodrug application for several cycles to even enhance and prolong the therapeutic effect. CONCLUSIONS/SIGNIFICANCE: In conclusion, lentiviral pseudotyped vectors are promising candidates for gene therapy of glioma in patients. The inefficient gene delivery by gammaretroviral vectors is in line with the results obtained in clinical therapy for GBM and thus confirms the high reproducibility of the invasive glioma animal model for translational research.",2009 Jul 20,"['Huszthy, Peter C.', 'Giroglou, Tsanan', 'Tsinkalovsky, Oleg', 'Euskirchen, Philipp', 'Skaftnesmo, Kai Ove', 'Bjerkvig, Rolf', 'von Laer, Dorothee', 'Miletic, Hrvoje']",PLoS One,,,True
d0ce640c27c2c8ef5f83e71bec07d829327d69d6,PMC,Protein Never in Mitosis Gene A Interacting-1 regulates calpain activity and the degradation of cyclooxygenase-2 in endothelial cells,http://dx.doi.org/10.1186/1476-9255-6-20,PMC2708161,19545424,CC BY,"BACKGROUND: The peptidyl-proline isomerase, Protein Never in Mitosis Gene A Interacting-1 (PIN1), regulates turnover of inducible nitric oxide synthase (iNOS) in murine aortic endothelial cells (MAEC) stimulated with E. coli endotoxin (LPS) and interferon-γ (IFN). Degradation of iNOS was reduced by a calpain inhibitor, suggesting that PIN1 may affect induction of other calpain-sensitive inflammatory proteins, such as cyclooxygenase (COX)-2, in MAEC. METHODS: MAEC, transduced with lentivirus encoding an inactive control short hairpin (sh) RNA or one targeting PIN1 that reduced PIN1 by 85%, were used. Cells were treated with LPS/IFN, calpain inhibitors (carbobenzoxy-valinyl-phenylalaninal (zVF), PD150606), cycloheximide and COX inhibitors to determine the effect of PIN1 depletion on COX-2 and calpain. RESULTS: LPS or IFN alone did not induce COX-2. However, treatment with 10 μg LPS plus 20 ng IFN per ml induced COX-2 protein 10-fold in Control shRNA MAEC. Induction was significantly greater (47-fold) in PIN1 shRNA cells. COX-2-dependent prostaglandin E2 production increased 3-fold in KD MAEC, but did not increase in Control cells. The additional increase in COX-2 protein due to PIN1 depletion was post-transcriptional, as induction of COX-2 mRNA by LPS/IFN was the same in cells containing or lacking PIN1. Instead, the loss of COX-2 protein, after treatment with cycloheximide to block protein synthesis, was reduced in cells lacking PIN1 in comparison with Control cells, indicating that degradation of the enzyme was reduced. zVF and PD150606 each enhanced the induction of COX-2 by LPS/IFN. zVF also slowed the loss of COX-2 after treatment with cycloheximide, and COX-2 was degraded by exogenous μ-calpain in vitro. In contrast to iNOS, physical interaction between COX-2 and PIN1 was not detected, suggesting that effects of PIN1 on calpain, rather than COX-2 itself, affect COX-2 degradation. While cathepsin activity was unaltered, depletion of PIN1 reduced calpain activity by 55% in comparison with Control shRNA cells. CONCLUSION: PIN1 reduced calpain activity and slowed the degradation of COX-2 in MAEC, an effect recapitulated by an inhibitor of calpain. Given the sensitivity of COX-2 and iNOS to calpain, PIN1 may normally limit induction of these and other calpain substrates by maintaining calpain activity in endothelial cells.",2009 Jun 22,"['Liu, Tongzheng', 'Schneider, Ryan A', 'Shah, Vaibhav', 'Huang, Yongcheng', 'Likhotvorik, Rostislav I', 'Keshvara, Lakhu', 'Hoyt, Dale G']",J Inflamm (Lond),,,True
b15e513ac2f5696b1e51324fb0a3118c44a6a9e9,PMC,Models of epidemics: when contact repetition and clustering should be included,http://dx.doi.org/10.1186/1742-4682-6-11,PMC2709892,19563624,CC BY,"BACKGROUND: The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. METHODS: We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. RESULTS: The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. CONCLUSION: We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.",2009 Jun 29,"['Smieszek, Timo', 'Fiebig, Lena', 'Scholz, Roland W']",Theor Biol Med Model,,,True
2b4187e81b56790a8c7390d631eb8081c0ab5c2b,PMC,Models of epidemics: when contact repetition and clustering should be included,http://dx.doi.org/10.1186/1742-4682-6-11,PMC2709892,19563624,CC BY,"BACKGROUND: The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. METHODS: We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. RESULTS: The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. CONCLUSION: We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.",2009 Jun 29,"['Smieszek, Timo', 'Fiebig, Lena', 'Scholz, Roland W']",Theor Biol Med Model,,,False
d0235ece6d613b700d5c4b369eaecb2dc81e5168,PMC,Models of epidemics: when contact repetition and clustering should be included,http://dx.doi.org/10.1186/1742-4682-6-11,PMC2709892,19563624,CC BY,"BACKGROUND: The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. METHODS: We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. RESULTS: The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. CONCLUSION: We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.",2009 Jun 29,"['Smieszek, Timo', 'Fiebig, Lena', 'Scholz, Roland W']",Theor Biol Med Model,,,False
86a5eec529af27298f88a24a32561946cb2e8f8d,PMC,Models of epidemics: when contact repetition and clustering should be included,http://dx.doi.org/10.1186/1742-4682-6-11,PMC2709892,19563624,CC BY,"BACKGROUND: The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. METHODS: We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. RESULTS: The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. CONCLUSION: We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.",2009 Jun 29,"['Smieszek, Timo', 'Fiebig, Lena', 'Scholz, Roland W']",Theor Biol Med Model,,,False
754eb3d52a722efaeee91ef19bba2d5c62fe0eae,PMC,Models of epidemics: when contact repetition and clustering should be included,http://dx.doi.org/10.1186/1742-4682-6-11,PMC2709892,19563624,CC BY,"BACKGROUND: The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. METHODS: We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. RESULTS: The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. CONCLUSION: We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.",2009 Jun 29,"['Smieszek, Timo', 'Fiebig, Lena', 'Scholz, Roland W']",Theor Biol Med Model,,,False
82f3e5abcabd0756aae8c054832a80658915bde3,PMC,Rapid and High-Throughput pan-Orthopoxvirus Detection and Identification using PCR and Mass Spectrometry,http://dx.doi.org/10.1371/journal.pone.0006342,PMC2710004,19623263,CC BY,"The genus Orthopoxvirus contains several species of related viruses, including the causative agent of smallpox (Variola virus). In addition to smallpox, several other members of the genus are capable of causing human infection, including monkeypox, cowpox, and other zoonotic rodent-borne poxviruses. Therefore, a single assay that can accurately identify all orthopoxviruses could provide a valuable tool for rapid broad orthopovirus identification. We have developed a pan-Orthopoxvirus assay for identification of all members of the genus based on four PCR reactions targeting Orthopoxvirus DNA and RNA helicase and polymerase genes. The amplicons are detected using electrospray ionization-mass spectrometry (PCR/ESI-MS) on the Ibis T5000 system. We demonstrate that the assay can detect and identify a diverse collection of orthopoxviruses, provide sub-species information and characterize viruses from the blood of rabbitpox infected rabbits. The assay is sensitive at the stochastic limit of PCR and detected virus in blood containing approximately six plaque-forming units per milliliter from a rabbitpox virus-infected rabbit.",2009 Jul 22,"['Eshoo, Mark W.', 'Whitehouse, Chris A.', 'Nalca, Aysegul', 'Zoll, Scott', 'Ecker, Joseph A.', 'Hall, Thomas A.', 'Pennella, Thuy-Trang D.', 'Duncan, David D.', 'Desai, Anjali', 'Moradi, Emily K.', 'Rudnick, Karl', 'Libby, Brian', 'Ranken, Raymond', 'Sampath, Rangarajan', 'Hofstadler, Steven A.', 'Ecker, David J.', 'Blyn, Lawrence B.']",PLoS One,,,True
49b325fc505d265149ed0c2e9131662626c16939,PMC,Pandemic influenza: implications for occupational medicine,http://dx.doi.org/10.1186/1745-6673-4-15,PMC2710320,19549302,CC BY,"This article reviews the biological and occupational medicine literature related to H5N1 pandemic influenza and its impact on infection control, cost and business continuity in settings outside the health care community. The literature on H5N1 biology is reviewed including the treatment and infection control mechanisms as they pertain to occupational medicine. Planning activity for the potential arrival of pandemic avian influenza is growing rapidly. Much has been published on the molecular biology of H5N1 but there remains a paucity of literature on the occupational medicine impacts to organizations. This review summarizes some of the basic science surrounding H5N1 influenza and raises some key concerns in pandemic planning for the occupational medicine professional. Workplaces other than health care settings will be impacted greatly by an H5N1 pandemic and the occupational physician will play an essential role in corporate preparation, response, and business continuity strategies.",2009 Jun 23,"['Journeay, W Shane', 'Burnstein, Matthew D']",J Occup Med Toxicol,,,True
8d095d0275e474dbb9d9b63a75591ff2c0667d73,PMC,Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection,http://dx.doi.org/10.1371/journal.pone.0006355,PMC2712091,19633719,CC BY,"BACKGROUND: Human rhinoviruses (HRVs) are a highly prevalent cause of acute respiratory infection in children. They are classified into at least three species, HRV-A, HRV-B and HRV-C, which are characterized by sequencing the 5′ untranslated region (UTR) or the VP4/VP2 region of the genome. Given the increased interest for novel HRV strain identification and their worldwide distribution, we have carried out clinical and molecular diagnosis of HRV strains in a 2-year study of children with acute respiratory infection visiting one district hospital in Shanghai. METHODOLOGY/FINDINGS: We cloned and sequenced a 924-nt fragment that covered part of the 5′UTR and the VP4/VP2 capsid genes. Sixty-four HRV-infected outpatients were diagnosed amongst 827 children with acute low respiratory tract infection. Two samples were co-infected with HRV-A and HRV-B or HRV-C. By comparative analysis of the VP4/VP2 sequences of the 66 HRVs, we showed a high diversity of strains in HRV-A and HRV-B species, and a prevalence of 51.5% of strains that belonged to the recently identified HRV-C species. When analyzing a fragment of the 5′ UTR, we characterized at least two subspecies of HRV-C: HRV-Cc, which clustered differently from HRV-A and HRV-B, and HRV-Ca, which resulted from previous recombination in this region with sequences related to HRV-A. The full-length sequence of one strain of each HRV-Ca and HRV-Cc subspecies was obtained for comparative analysis. We confirmed the close relationship of their structural proteins but showed apparent additional recombination events in the 2A gene and 3′UTR of the HRV-Ca strain. Double or triple infections with HRV-C and respiratory syncytial virus and/or bocavirus were diagnosed in 33.3% of the HRV-infected patients, but no correlation with severity of clinical outcome was observed. CONCLUSION: Our study showed a high diversity of HRV strains that cause bronchitis and pneumonia in children. A predominance of HRV-C over HRV-A and HRV-B was observed, and two subspecies of HRV-C were identified, the diversity of which seemed to be related to recombination with former HRV-A strains. None of the HRV-C strains appeared to have a higher clinical impact than HRV-A or HRV-B on respiratory compromise.",2009 Jul 27,"['Huang, Ting', 'Wang, Wei', 'Bessaud, Mael', 'Ren, Peijun', 'Sheng, Jun', 'Yan, Huajie', 'Zhang, Jing', 'Lin, Xin', 'Wang, Yongjin', 'Delpeyroux, Francis', 'Deubel, Vincent']",PLoS One,,,True
f415c477bac80d18eec2b6775efd8d660a7688ba,PMC,Novel Mechanistic Insights into Viral Modulation of Immune Receptor Signaling,http://dx.doi.org/10.1371/journal.ppat.1000404,PMC2712764,19649322,CC BY,,2009 Jul 31,"Sigalov, Alexander B.",PLoS Pathog,,,True
347d44e7849c7abbf867722925ffc5996b0f9a11,PMC,Influence of Dendritic Cells on Viral Pathogenicity,http://dx.doi.org/10.1371/journal.ppat.1000384,PMC2712770,19649323,CC BY,"Although most viral infections cause minor, if any, symptoms, a certain number result in serious illness. Viral disease symptoms result both from direct viral replication within host cells and from indirect immunopathological consequences. Dendritic cells (DCs) are key determinants of viral disease outcome; they activate immune responses during viral infection and direct T cells toward distinct T helper type responses. Certain viruses are able to skew cytokine secretion by DCs inducing and/or downregulating the immune system with the aim of facilitating and prolonging release of progeny. Thus, the interaction of DCs with viruses most often results in the absence of disease or complete recovery when natural functions of DCs prevail, but may lead to chronic illness or death when these functions are outmanoeuvred by viruses in the exploitation of DCs.",2009 Jul 31,"['Freer, Giulia', 'Matteucci, Donatella']",PLoS Pathog,,,True
baa419d7be9ab01f85ff19c108df77103b29cb50,PMC,Constitutional Flavonoids Derived from Epimedium Dose-Dependently Reduce Incidence of Steroid-Associated Osteonecrosis Not via Direct Action by Themselves on Potential Cellular Targets,http://dx.doi.org/10.1371/journal.pone.0006419,PMC2713419,19641620,CC BY,"Intravascular-thrombosis and extravascular-lipid-deposit are the two key pathogenic events considered to interrupt intraosseous blood supply during development of steroid-associated osteonecrosis (ON). However, there are no clinically employed agents capable of simultaneously targeting these two key pathogenic events. The present experimental study demonstrated that constitutional flavonoid glycosides derived from herb Epimedium (EF, composed of seven flavonoid compounds with common stem nuclear) exerted dose-dependent effect on inhibition of both thrombosis and lipid-deposition and accordingly reducing incidence of steroid-associated ON in rabbits, which was not via direct action by themselves rather by their common metabolite on potential cellular targets involved in the two pathogenic pathways. The underlying mechanism could be explained by counteracting endothelium injury and excessive adipogenesis. These findings encourage designing clinical trials to investigate potential of EF in prevention of steroid-associated ON.",2009 Jul 29,"['Zhang, Ge', 'Wang, Xin-Luan', 'Sheng, Hui', 'Xie, Xin-Hui', 'He, Yi-Xin', 'Yao, Xin-Sheng', 'Li, Zi-Rong', 'Lee, Kwong-Man', 'He, Wei', 'Leung, Kwok-Sui', 'Qin, Ling']",PLoS One,,,True
8ef0cd02635a7841b2b26cb159038427c31c39b3,PMC,Is dengue a threat to the blood supply?,http://dx.doi.org/10.1111/j.1365-3148.2009.00916.x,PMC2713854,19392949,CC BY,"Dengue is the most common arthropod-borne infection worldwide, affecting at least 50 million people every year and endemic in more than 100 countries. The dengue virus is a single-stranded RNA virus with four major serotypes. Infection with one serotype confers homotypic immunity but not heterologous immunity, and secondary infection with another serotype may lead to more severe disease. The major route of transmission occurs through the Aedes aegypti mosquito vector, but dengue has also been transmitted through blood transfusion and organ transplantation. Infection results in a spectrum of clinical illness ranging from asymptomatic infection, undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF) to dengue shock syndrome (DSS). Dengue is spreading rapidly to new areas and with increasing frequency of major outbreaks. A trend has also been observed towards increasing age among infected patients. This will impact blood supply availability as more blood donors are deferred because of dengue infection or exposure to infection. The risk of transmission through transfusion of blood from asymptomatic viraemic donors will also increase. Although screening tests for dengue and effective pathogen reduction processes are now available for the blood supply, the value of implementing these costly measures needs to be carefully considered. Demand for platelets and fresh frozen plasma will rise with increasing number of DHF/DSS. Evidence-based guidelines for the clinical use of these blood components in the management of patients with DHF/DSS have not been well established, and inappropriate use will contribute to the challenges faced by blood services.",2009 Apr,"['Teo, D', 'Ng, L C', 'Lam, S']",Transfus Med,,,True
f318f02676fa086210640feb3fb488ae9522ba95,PMC,Structure of the C-terminal domain of nsp4 from feline coronavirus,http://dx.doi.org/10.1107/S0907444909018253,PMC2714721,19622868,CC BY,"Coronaviruses are a family of positive-stranded RNA viruses that includes important pathogens of humans and other animals. The large coronavirus genome (26–31 kb) encodes 15–16 nonstructural proteins (nsps) that are derived from two replicase polyproteins by autoproteolytic processing. The nsps assemble into the viral replication–transcription complex and nsp3, nsp4 and nsp6 are believed to anchor this enzyme complex to modified intracellular membranes. The largest part of the coronavirus nsp4 subunit is hydrophobic and is predicted to be embedded in the membranes. In this report, a conserved C-terminal domain (∼100 amino-acid residues) has been delineated that is predicted to face the cytoplasm and has been isolated as a soluble domain using library-based construct screening. A prototypical crystal structure at 2.8 Å resolution was obtained using nsp4 from feline coronavirus. Unmodified and SeMet-substituted proteins were crystallized under similar conditions, resulting in tetragonal crystals that belonged to space group P4(3). The phase problem was initially solved by single isomorphous replacement with anomalous scattering (SIRAS), followed by molecular replacement using a SIRAS-derived composite model. The structure consists of a single domain with a predominantly α-helical content displaying a unique fold that could be engaged in protein–protein interactions.",2009 Aug 1,"['Manolaridis, Ioannis', 'Wojdyla, Justyna A.', 'Panjikar, Santosh', 'Snijder, Eric J.', 'Gorbalenya, Alexander E.', 'Berglind, Hanna', 'Nordlund, Pär', 'Coutard, Bruno', 'Tucker, Paul A.']",Acta Crystallogr D Biol Crystallogr,,,True
e296fa71274bad6cabcf683a2ba47e58b1326877,PMC,Musings on privacy issues in health research involving disaggregate geographic data about individuals,http://dx.doi.org/10.1186/1476-072X-8-46,PMC2716332,19619311,CC BY,"This paper offers a state-of-the-art overview of the intertwined privacy, confidentiality, and security issues that are commonly encountered in health research involving disaggregate geographic data about individuals. Key definitions are provided, along with some examples of actual and potential security and confidentiality breaches and related incidents that captured mainstream media and public interest in recent months and years. The paper then goes on to present a brief survey of the research literature on location privacy/confidentiality concerns and on privacy-preserving solutions in conventional health research and beyond, touching on the emerging privacy issues associated with online consumer geoinformatics and location-based services. The 'missing ring' (in many treatments of the topic) of data security is also discussed. Personal information and privacy legislations in two countries, Canada and the UK, are covered, as well as some examples of recent research projects and events about the subject. Select highlights from a June 2009 URISA (Urban and Regional Information Systems Association) workshop entitled 'Protecting Privacy and Confidentiality of Geographic Data in Health Research' are then presented. The paper concludes by briefly charting the complexity of the domain and the many challenges associated with it, and proposing a novel, 'one stop shop' case-based reasoning framework to streamline the provision of clear and individualised guidance for the design and approval of new research projects (involving geographical identifiers about individuals), including crisp recommendations on which specific privacy-preserving solutions and approaches would be suitable in each case.",2009 Jul 20,"['Boulos, Maged N Kamel', 'Curtis, Andrew J', 'AbdelMalik, Philip']",Int J Health Geogr,,,True
b00ed3b8efc4531b84e5035419418056eea0799b,PMC,Musings on privacy issues in health research involving disaggregate geographic data about individuals,http://dx.doi.org/10.1186/1476-072X-8-46,PMC2716332,19619311,CC BY,"This paper offers a state-of-the-art overview of the intertwined privacy, confidentiality, and security issues that are commonly encountered in health research involving disaggregate geographic data about individuals. Key definitions are provided, along with some examples of actual and potential security and confidentiality breaches and related incidents that captured mainstream media and public interest in recent months and years. The paper then goes on to present a brief survey of the research literature on location privacy/confidentiality concerns and on privacy-preserving solutions in conventional health research and beyond, touching on the emerging privacy issues associated with online consumer geoinformatics and location-based services. The 'missing ring' (in many treatments of the topic) of data security is also discussed. Personal information and privacy legislations in two countries, Canada and the UK, are covered, as well as some examples of recent research projects and events about the subject. Select highlights from a June 2009 URISA (Urban and Regional Information Systems Association) workshop entitled 'Protecting Privacy and Confidentiality of Geographic Data in Health Research' are then presented. The paper concludes by briefly charting the complexity of the domain and the many challenges associated with it, and proposing a novel, 'one stop shop' case-based reasoning framework to streamline the provision of clear and individualised guidance for the design and approval of new research projects (involving geographical identifiers about individuals), including crisp recommendations on which specific privacy-preserving solutions and approaches would be suitable in each case.",2009 Jul 20,"['Boulos, Maged N Kamel', 'Curtis, Andrew J', 'AbdelMalik, Philip']",Int J Health Geogr,,,True
dcf12f1f76ae03b3107f00aadea540298105d312,PMC,Temporal Variability and Social Heterogeneity in Disease Transmission: The Case of SARS in Hong Kong,http://dx.doi.org/10.1371/journal.pcbi.1000471,PMC2717369,19696879,CC BY,"The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002–2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (±0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.",2009 Aug 21,"['Cori, Anne', 'Boëlle, Pierre-Yves', 'Thomas, Guy', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Comput Biol,,,True
1f47ecc5657834cf9676ecdfd1f3f170b204b9c0,PMC,Temporal Variability and Social Heterogeneity in Disease Transmission: The Case of SARS in Hong Kong,http://dx.doi.org/10.1371/journal.pcbi.1000471,PMC2717369,19696879,CC BY,"The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002–2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (±0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.",2009 Aug 21,"['Cori, Anne', 'Boëlle, Pierre-Yves', 'Thomas, Guy', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Comput Biol,,,False
933a1b843db9eb0d98835f9359622ba8cb8bdc05,PMC,Temporal Variability and Social Heterogeneity in Disease Transmission: The Case of SARS in Hong Kong,http://dx.doi.org/10.1371/journal.pcbi.1000471,PMC2717369,19696879,CC BY,"The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002–2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (±0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.",2009 Aug 21,"['Cori, Anne', 'Boëlle, Pierre-Yves', 'Thomas, Guy', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Comput Biol,,,True
d7a89e6c00e3e927a2c521c347629fcc0950a5d6,PMC,Temporal Variability and Social Heterogeneity in Disease Transmission: The Case of SARS in Hong Kong,http://dx.doi.org/10.1371/journal.pcbi.1000471,PMC2717369,19696879,CC BY,"The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002–2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (±0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.",2009 Aug 21,"['Cori, Anne', 'Boëlle, Pierre-Yves', 'Thomas, Guy', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Comput Biol,,,False
5a55cfceb7365142481967c11c4f70b359a1e4b1,PMC,Temporal Variability and Social Heterogeneity in Disease Transmission: The Case of SARS in Hong Kong,http://dx.doi.org/10.1371/journal.pcbi.1000471,PMC2717369,19696879,CC BY,"The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002–2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (±0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.",2009 Aug 21,"['Cori, Anne', 'Boëlle, Pierre-Yves', 'Thomas, Guy', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Comput Biol,,,True
25f4a5990fcb174f80bc472629eb47be50d5b3f7,PMC,"Distribution and seasonality of rhinovirus and other respiratory viruses in a cross-section of asthmatic children in Trinidad, West Indies",http://dx.doi.org/10.1186/1824-7288-35-16,PMC2717562,19555507,CC BY,"BACKGROUND: Childhood asthma in the Caribbean is advancing in prevalence and morbidity. Though viral respiratory tract infections are reported triggers for exacerbations, information on these infections with asthma is sparse in Caribbean territories. We examined the distribution of respiratory viruses and their association with seasons in acute and stable asthmatic children in Trinidad. METHODS: In a cross-sectional study of 70 wheezing children attending the emergency department for nebulisation and 80 stable control subjects (2 to 16 yr of age) in the asthma clinic, nasal specimens were collected during the dry (n = 38, January to May) and rainy (n = 112, June to December) seasons. A multitarget, sensitive, specific high-throughput Respiratory MultiCode assay tested for respiratory-virus sequences for eight distinct groups: human rhinovirus, respiratory syncytial virus, parainfluenza virus, influenza virus, metapneumovirus, adenovirus, coronavirus, and enterovirus. RESULTS: Wheezing children had a higher [χ(2 )= 5.561, p = 0.018] prevalence of respiratory viruses compared with stabilized asthmatics (34.3% (24) versus (vs.) 17.5% (14)). Acute asthmatics were thrice as likely to be infected with a respiratory virus (OR = 2.5, 95% CI = 1.2 – 5.3). The predominant pathogens detected in acute versus stable asthmatics were the rhinovirus (RV) (n = 18, 25.7% vs. n = 7, 8.8%; p = 0.005), respiratory syncytial virus B (RSV B) (n = 2, 2.9% vs. n = 4, 5.0%), and enterovirus (n = 1, 1.4% vs. n = 2, 2.5%). Strong odds for rhinoviral infection were observed among nebulised children compared with stable asthmatics (p = 0.005, OR = 3.6, 95% CI = 1.4 – 9.3,). RV was prevalent throughout the year (Dry, n = 6, 15.8%; Rainy, n = 19, 17.0%) and without seasonal association [χ(2 )= 0.028, p = 0.867]. However it was the most frequently detected virus [Dry = 6/10, (60.0%); Rainy = 19/28, (67.9%)] in both seasons. CONCLUSION: Emergent wheezing illnesses during childhood can be linked to infection with rhinovirus in Trinidad's tropical environment. Viral-induced exacerbations of asthma are independent of seasons in this tropical climate. Further clinical and virology investigations are recommended on the role of infections with the rhinovirus in Caribbean childhood wheeze.",2009 Jun 25,"['Matthew, Jason', 'Pinto Pereira, Lexley M', 'Pappas, Tressa E', 'Swenson, Cheri A', 'Grindle, Kris A', 'Roberg, Kathy A', 'Lemanske, Robert F', 'Lee, Wai-Ming', 'Gern, James E']",Ital J Pediatr,,,True
c77f37d083293f7461d47471caa670e765270948,PMC,Using LongSAGE to Detect Biomarkers of Cervical Cancer Potentially Amenable to Optical Contrast Agent Labelling,,PMC2717845,19662225,CC BY,"Sixteen longSAGE libraries from four different clinical stages of cervical intraepithelial neoplasia have enabled us to identify novel cell-surface biomarkers indicative of CIN stage. By comparing gene expression profiles of cervical tissue at early and advanced stages of CIN, several genes are identified to be novel genetic markers. We present fifty-six cell-surface gene products differentially expressed during progression of CIN. These cell surface proteins are being examined to establish their capacity for optical contrast agent binding. Contrast agent visualization will allow real-time assessment of the physiological state of the disease process bringing vast benefit to cancer care. The data discussed in this publication have been submitted to NCBIs Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) and are accessible through GEO Series accession number GSE6252.",2007 Dec 11,"['Kneller, Julie M.', 'Ehlen, Thomas', 'Matisic, Jasenka P.', 'Miller, Dianne', 'Van Niekerk, Dirk', 'Lam, Wan L.', 'Marra, Marco', 'Richards-Kortum, Rebecca', 'Follen, Michelle', 'MacAulay, Calum', 'Jones, Steven J. M.']",Biomark Insights,,,True
541e4b9cc19cdef991c78ff39e6ad79c1f5ecb09,PMC,The role of NH(4)Cl and cysteine proteases in Human Papillomavirus type 16 infection,http://dx.doi.org/10.1186/1743-422X-6-109,PMC2718874,19619315,CC BY,"BACKGROUND: The infectious pathway of the non-enveloped Human Papillomavirus Type 16 (HPV16) includes binding to the cell surface, clathrin-mediated endocytosis, and penetration into an endosome. HPV16 infection was shown to decrease in the presence of the lysosomotrophic neutralizing agent ammonium chloride (NH(4)Cl). NH(4)Cl neutralizes acidic endo-lysosome compartments, thus suggesting that pH was responsible for PV capsid conformational changes leading endosome escape. RESULTS: However, our data suggested that NH(4)Cl blocked infection by preventing the movement of PV viral particles from the early endosome to the caveosome as was shown for JC virus [1,2]. We have confirmed that HPV 16 infection requires the trafficking of reporter-virions to the caveosome as is the case for BPV1 [3,4]. In this manuscript we propose that the observed decrease in infection of PV in the presence of NH(4)Cl was due to a loss of movement of reporter-virions to caveosomes. We also demonstrate that cysteine proteases are involved in the infectious process, and that cathepsin B treatment of viral particles was shown to overcome the block of infection observed in the presence of furin inhibition. We confirmed the need for cathepsin B in HPV16 infection using cathepsin B null mouse embryonic fibroblasts. CONCLUSION: We present data that suggest HPV16 infection is in part mediated by cysteine proteases, and that NH(4)Cl blocks the intracellular trafficking of infectious viral particles. To our knowledge this is the first demonstration that cysteine proteases influence the infection of a non-enveloped virus.",2009 Jul 20,"['Dabydeen, Sarah A', 'Meneses, Patricio I']",Virol J,,,True
013602fc7c2a0e0c4fcfb0e50f6b09fd2c2faa34,PMC,The role of NH(4)Cl and cysteine proteases in Human Papillomavirus type 16 infection,http://dx.doi.org/10.1186/1743-422X-6-109,PMC2718874,19619315,CC BY,"BACKGROUND: The infectious pathway of the non-enveloped Human Papillomavirus Type 16 (HPV16) includes binding to the cell surface, clathrin-mediated endocytosis, and penetration into an endosome. HPV16 infection was shown to decrease in the presence of the lysosomotrophic neutralizing agent ammonium chloride (NH(4)Cl). NH(4)Cl neutralizes acidic endo-lysosome compartments, thus suggesting that pH was responsible for PV capsid conformational changes leading endosome escape. RESULTS: However, our data suggested that NH(4)Cl blocked infection by preventing the movement of PV viral particles from the early endosome to the caveosome as was shown for JC virus [1,2]. We have confirmed that HPV 16 infection requires the trafficking of reporter-virions to the caveosome as is the case for BPV1 [3,4]. In this manuscript we propose that the observed decrease in infection of PV in the presence of NH(4)Cl was due to a loss of movement of reporter-virions to caveosomes. We also demonstrate that cysteine proteases are involved in the infectious process, and that cathepsin B treatment of viral particles was shown to overcome the block of infection observed in the presence of furin inhibition. We confirmed the need for cathepsin B in HPV16 infection using cathepsin B null mouse embryonic fibroblasts. CONCLUSION: We present data that suggest HPV16 infection is in part mediated by cysteine proteases, and that NH(4)Cl blocks the intracellular trafficking of infectious viral particles. To our knowledge this is the first demonstration that cysteine proteases influence the infection of a non-enveloped virus.",2009 Jul 20,"['Dabydeen, Sarah A', 'Meneses, Patricio I']",Virol J,,,False
e4fa5f794163e9b5cd12131d334f83a7818e0838,PMC,The role of NH(4)Cl and cysteine proteases in Human Papillomavirus type 16 infection,http://dx.doi.org/10.1186/1743-422X-6-109,PMC2718874,19619315,CC BY,"BACKGROUND: The infectious pathway of the non-enveloped Human Papillomavirus Type 16 (HPV16) includes binding to the cell surface, clathrin-mediated endocytosis, and penetration into an endosome. HPV16 infection was shown to decrease in the presence of the lysosomotrophic neutralizing agent ammonium chloride (NH(4)Cl). NH(4)Cl neutralizes acidic endo-lysosome compartments, thus suggesting that pH was responsible for PV capsid conformational changes leading endosome escape. RESULTS: However, our data suggested that NH(4)Cl blocked infection by preventing the movement of PV viral particles from the early endosome to the caveosome as was shown for JC virus [1,2]. We have confirmed that HPV 16 infection requires the trafficking of reporter-virions to the caveosome as is the case for BPV1 [3,4]. In this manuscript we propose that the observed decrease in infection of PV in the presence of NH(4)Cl was due to a loss of movement of reporter-virions to caveosomes. We also demonstrate that cysteine proteases are involved in the infectious process, and that cathepsin B treatment of viral particles was shown to overcome the block of infection observed in the presence of furin inhibition. We confirmed the need for cathepsin B in HPV16 infection using cathepsin B null mouse embryonic fibroblasts. CONCLUSION: We present data that suggest HPV16 infection is in part mediated by cysteine proteases, and that NH(4)Cl blocks the intracellular trafficking of infectious viral particles. To our knowledge this is the first demonstration that cysteine proteases influence the infection of a non-enveloped virus.",2009 Jul 20,"['Dabydeen, Sarah A', 'Meneses, Patricio I']",Virol J,,,False
a28137c598e91a3214a936363e59a1ee1f0717ef,PMC,The role of NH(4)Cl and cysteine proteases in Human Papillomavirus type 16 infection,http://dx.doi.org/10.1186/1743-422X-6-109,PMC2718874,19619315,CC BY,"BACKGROUND: The infectious pathway of the non-enveloped Human Papillomavirus Type 16 (HPV16) includes binding to the cell surface, clathrin-mediated endocytosis, and penetration into an endosome. HPV16 infection was shown to decrease in the presence of the lysosomotrophic neutralizing agent ammonium chloride (NH(4)Cl). NH(4)Cl neutralizes acidic endo-lysosome compartments, thus suggesting that pH was responsible for PV capsid conformational changes leading endosome escape. RESULTS: However, our data suggested that NH(4)Cl blocked infection by preventing the movement of PV viral particles from the early endosome to the caveosome as was shown for JC virus [1,2]. We have confirmed that HPV 16 infection requires the trafficking of reporter-virions to the caveosome as is the case for BPV1 [3,4]. In this manuscript we propose that the observed decrease in infection of PV in the presence of NH(4)Cl was due to a loss of movement of reporter-virions to caveosomes. We also demonstrate that cysteine proteases are involved in the infectious process, and that cathepsin B treatment of viral particles was shown to overcome the block of infection observed in the presence of furin inhibition. We confirmed the need for cathepsin B in HPV16 infection using cathepsin B null mouse embryonic fibroblasts. CONCLUSION: We present data that suggest HPV16 infection is in part mediated by cysteine proteases, and that NH(4)Cl blocks the intracellular trafficking of infectious viral particles. To our knowledge this is the first demonstration that cysteine proteases influence the infection of a non-enveloped virus.",2009 Jul 20,"['Dabydeen, Sarah A', 'Meneses, Patricio I']",Virol J,,,False
44efcab56950c5fa796c22e0c46f3537adcf9171,PMC,The role of NH(4)Cl and cysteine proteases in Human Papillomavirus type 16 infection,http://dx.doi.org/10.1186/1743-422X-6-109,PMC2718874,19619315,CC BY,"BACKGROUND: The infectious pathway of the non-enveloped Human Papillomavirus Type 16 (HPV16) includes binding to the cell surface, clathrin-mediated endocytosis, and penetration into an endosome. HPV16 infection was shown to decrease in the presence of the lysosomotrophic neutralizing agent ammonium chloride (NH(4)Cl). NH(4)Cl neutralizes acidic endo-lysosome compartments, thus suggesting that pH was responsible for PV capsid conformational changes leading endosome escape. RESULTS: However, our data suggested that NH(4)Cl blocked infection by preventing the movement of PV viral particles from the early endosome to the caveosome as was shown for JC virus [1,2]. We have confirmed that HPV 16 infection requires the trafficking of reporter-virions to the caveosome as is the case for BPV1 [3,4]. In this manuscript we propose that the observed decrease in infection of PV in the presence of NH(4)Cl was due to a loss of movement of reporter-virions to caveosomes. We also demonstrate that cysteine proteases are involved in the infectious process, and that cathepsin B treatment of viral particles was shown to overcome the block of infection observed in the presence of furin inhibition. We confirmed the need for cathepsin B in HPV16 infection using cathepsin B null mouse embryonic fibroblasts. CONCLUSION: We present data that suggest HPV16 infection is in part mediated by cysteine proteases, and that NH(4)Cl blocks the intracellular trafficking of infectious viral particles. To our knowledge this is the first demonstration that cysteine proteases influence the infection of a non-enveloped virus.",2009 Jul 20,"['Dabydeen, Sarah A', 'Meneses, Patricio I']",Virol J,,,False
a0f9f661ac6e00d87e9b40d93ee4a4ae4605139f,PMC,The role of NH(4)Cl and cysteine proteases in Human Papillomavirus type 16 infection,http://dx.doi.org/10.1186/1743-422X-6-109,PMC2718874,19619315,CC BY,"BACKGROUND: The infectious pathway of the non-enveloped Human Papillomavirus Type 16 (HPV16) includes binding to the cell surface, clathrin-mediated endocytosis, and penetration into an endosome. HPV16 infection was shown to decrease in the presence of the lysosomotrophic neutralizing agent ammonium chloride (NH(4)Cl). NH(4)Cl neutralizes acidic endo-lysosome compartments, thus suggesting that pH was responsible for PV capsid conformational changes leading endosome escape. RESULTS: However, our data suggested that NH(4)Cl blocked infection by preventing the movement of PV viral particles from the early endosome to the caveosome as was shown for JC virus [1,2]. We have confirmed that HPV 16 infection requires the trafficking of reporter-virions to the caveosome as is the case for BPV1 [3,4]. In this manuscript we propose that the observed decrease in infection of PV in the presence of NH(4)Cl was due to a loss of movement of reporter-virions to caveosomes. We also demonstrate that cysteine proteases are involved in the infectious process, and that cathepsin B treatment of viral particles was shown to overcome the block of infection observed in the presence of furin inhibition. We confirmed the need for cathepsin B in HPV16 infection using cathepsin B null mouse embryonic fibroblasts. CONCLUSION: We present data that suggest HPV16 infection is in part mediated by cysteine proteases, and that NH(4)Cl blocks the intracellular trafficking of infectious viral particles. To our knowledge this is the first demonstration that cysteine proteases influence the infection of a non-enveloped virus.",2009 Jul 20,"['Dabydeen, Sarah A', 'Meneses, Patricio I']",Virol J,,,False
1a9fdd51745b132ee92107b4e9c68597d3767b7e,PMC,Beyond traditional surveillance: applying syndromic surveillance to developing settings – opportunities and challenges,http://dx.doi.org/10.1186/1471-2458-9-242,PMC2718884,19607669,CC BY,"BACKGROUND: All countries need effective disease surveillance systems for early detection of outbreaks. The revised International Health Regulations [IHR], which entered into force for all 194 World Health Organization member states in 2007, have expanded traditional infectious disease notification to include surveillance for public health events of potential international importance, even if the causative agent is not yet known. However, there are no clearly established guidelines for how countries should conduct this surveillance, which types of emerging disease syndromes should be reported, nor any means for enforcement. DISCUSSION: The commonly established concept of syndromic surveillance in developed regions encompasses the use of pre-diagnostic information in a near real time fashion for further investigation for public health action. Syndromic surveillance is widely used in North America and Europe, and is typically thought of as a highly complex, technology driven automated tool for early detection of outbreaks. Nonetheless, low technology applications of syndromic surveillance are being used worldwide to augment traditional surveillance. SUMMARY: In this paper, we review examples of these novel applications in the detection of vector-borne diseases, foodborne illness, and sexually transmitted infections. We hope to demonstrate that syndromic surveillance in its basic version is a feasible and effective tool for surveillance in developing countries and may facilitate compliance with the new IHR guidelines.",2009 Jul 16,"['May, Larissa', 'Chretien, Jean-Paul', 'Pavlin, Julie A']",BMC Public Health,,,True
f9a61ae749c3d53492b38119c9fbe5f0e448b52a,PMC,What infection control measures will people carry out to reduce transmission of pandemic influenza? A focus group study,http://dx.doi.org/10.1186/1471-2458-9-258,PMC2720966,19627568,CC BY,"BACKGROUND: Pandemic influenza poses a future health threat against which infection control behaviours may be an important defence. However, there is little qualitative research examining perceptions of infection control measures in the context of pandemic influenza. METHODS: Eight focus groups and one interview were conducted with a purposive sample of 31 participants. Participants were invited to discuss their perceptions of infection transmission and likely adherence to infection control measures in both non-pandemic and pandemic contexts. Infection control measures discussed included handwashing, social distancing and cough hygiene (e.g. covering mouth, disposing of tissues immediately etc.). RESULTS: Thematic analysis revealed that although participants were knowledgeable about infection transmission, most expressed unfavourable attitudes toward control behaviours in non-pandemic situations. However, with the provision of adequate education about control measures and appropriate practical support (e.g. memory aids, access to facilities), most individuals report that they are likely to adhere to infection control protocols in the event of a pandemic. Of the behaviours likely to influence infection transmission, handwashing was regarded by our participants as more feasible than cough and sneeze hygiene and more acceptable than social distancing. CONCLUSION: Handwashing could prove a useful target for health promotion, but interventions to promote infection control may need to address a number of factors identified within this study as potential barriers to carrying out infection control behaviours.",2009 Jul 23,"['Morrison, Leanne G', 'Yardley, Lucy']",BMC Public Health,,,True
e1c0a2349d7445ba4cfd01185dbff3b8346afe45,PMC,What infection control measures will people carry out to reduce transmission of pandemic influenza? A focus group study,http://dx.doi.org/10.1186/1471-2458-9-258,PMC2720966,19627568,CC BY,"BACKGROUND: Pandemic influenza poses a future health threat against which infection control behaviours may be an important defence. However, there is little qualitative research examining perceptions of infection control measures in the context of pandemic influenza. METHODS: Eight focus groups and one interview were conducted with a purposive sample of 31 participants. Participants were invited to discuss their perceptions of infection transmission and likely adherence to infection control measures in both non-pandemic and pandemic contexts. Infection control measures discussed included handwashing, social distancing and cough hygiene (e.g. covering mouth, disposing of tissues immediately etc.). RESULTS: Thematic analysis revealed that although participants were knowledgeable about infection transmission, most expressed unfavourable attitudes toward control behaviours in non-pandemic situations. However, with the provision of adequate education about control measures and appropriate practical support (e.g. memory aids, access to facilities), most individuals report that they are likely to adhere to infection control protocols in the event of a pandemic. Of the behaviours likely to influence infection transmission, handwashing was regarded by our participants as more feasible than cough and sneeze hygiene and more acceptable than social distancing. CONCLUSION: Handwashing could prove a useful target for health promotion, but interventions to promote infection control may need to address a number of factors identified within this study as potential barriers to carrying out infection control behaviours.",2009 Jul 23,"['Morrison, Leanne G', 'Yardley, Lucy']",BMC Public Health,,,False
271eaab0cdf64e3274bd45a4264eeac8f2d1b0d1,PMC,Radiotherapy for oncologic emergencies on weekends: examining reasons for treatment and patterns of practice at a Canadian cancer centre,,PMC2722059,19672425,CC BY,"PURPOSE: Radiotherapy for oncologic emergencies is an important aspect of the management of cancer patients. These emergencies—which include malignant spinal cord compression, brain metastases, superior vena cava obstruction, and uncontrolled tumour hemorrhage —may require treatment outside of hospital hours, particularly on weekends and hospital holidays. To date, there remains no consensus among radiation oncologists regarding the indications and appropriateness of radiotherapy treatment on weekends, and treatment decisions remain largely subjective. The main aim of the present study was to document the incidence and indications for patients receiving emergency treatment on weekends or scheduled hospital holidays at a single institution. The secondary aim was to investigate the compliance of such treatment with the institution’s quality assurance policies, both local and provincial. METHODS: From September 1, 2002, to September 30, 2004, patients being treated over weekends (defined as commencing at 6 pm on a Friday and concluding at 8 am of the next scheduled workday) and hospital holidays were retrospectively identified using the Oncology Patient Information System scheduling module. Relevant patient data—including patient age, sex, primary cancer site, specific radiation field, rationale for treatment, referring hospital, total treatment dose, radiation dose fractionation, inpatient or outpatient status, and duration of treatment—were collected and subsequently analyzed. Comparison to local policy was performed subjectively. RESULTS: Over the 2-year period, 161 patients were prescribed urgent radiotherapy over a weekend or on a hospital holiday. Of this cohort, 68% were treated on both Saturday and Sunday, 22% on Saturday alone, and 10% on Sunday alone. Most patients presented with lung (31%), prostate (18%), and breast cancer (17%). The top reasons for referral for emergency weekend treatment included spinal cord compression (56%), brain metastases (15%), and superior vena cava obstruction (6%). Most of the indications for treatment generally followed the quality assurance policies implemented both locally and provincially. CONCLUSIONS: Patients treated over a weekend or on a hospital holiday were generally found to be treated with appropriate intent. Most treatment indications within this study both complied with provincial policy and showed a pattern of care similar to that seen in other studies in the literature. Local policy appears to be robust; however, policy improvements may allow for more cohesiveness across radiation oncologists in patterns of care in this important group of patients. Comparisons with practice at other institutions would be valuable and also a key step in developing sound guidelines for all members of the radiotherapy community to follow.",2009 Aug,"['Mitera, G.', 'Swaminath, A.', 'Wong, S.', 'Goh, P.', 'Robson, S.', 'Sinclair, E.', 'Danjoux, C.', 'Chow, E.']",Curr Oncol,,,True
9ebef419c2970287a5fd24ea38695453e0bbfffa,PMC,Retrospective analysis of nosocomial infections in the intensive care unit of a tertiary hospital in China during 2003 and 2007,http://dx.doi.org/10.1186/1471-2334-9-115,PMC2722662,19630992,CC BY,"BACKGROUND: Nosocomial infections are a major threat to patients in the intensive care unit (ICU). Limited data exist on the epidemiology of ICU-acquired infections in China. This retrospective study was carried out to determine the current status of nosocomial infection in China. METHODS: A retrospective review of nococomial infections in the ICU of a tertiary hospital in East China between 2003 and 2007 was performed. Nosocomial infections were defined according to the definitions of Centers for Disease Control and Prevention. The overall patient nosocomial infection rate, the incidence density rate of nosocomial infections, the excess length of stay, and distribution of nosocomial infection sites were determined. Then, pathogen and antimicrobial susceptibility profiles were further investigated. RESULTS: Among 1980 patients admitted over the period of time, the overall patient nosocomial infection rate was 26.8% or 51.0 per 1000 patient days., Lower respiratory tract infections (LRTI) accounted for most of the infections (68.4%), followed by urinary tract infections (UTI, 15.9%), bloodstream (BSI, 5.9%), and gastrointestinal tract (GI, 2.5%) infections. There was no significant change in LRTI, UTI and BSI infection rates during the 5 years. However, GI rate was significantly decreased from 5.5% in 2003 to 0.4% in 2007. In addition, A. baumannii, C. albicans and S. epidermidis were the most frequent pathogens isolated in patients with LRTIs, UTIs and BSIs, respectively. The rates of isolates resistant to commonly used antibiotics ranged from 24.0% to 93.1%. CONCLUSION: There was a high and relatively stable rate of nosocomial infections in the ICU of a tertiary hospital in China through year 2003–2007, with some differences in the distribution of the infection sites, and pathogen and antibiotic susceptibility profiles from those reported from the Western countries. Guidelines for surveillance and prevention of nosocomial infections must be implemented in order to reduce the rate.",2009 Jul 25,"['Ding, Ji-Guang', 'Sun, Qing-Feng', 'Li, Ke-Cheng', 'Zheng, Ming-Hua', 'Miao, Xiao-Hui', 'Ni, Wu', 'Hong, Liang', 'Yang, Jin-Xian', 'Ruan, Zhan-Wei', 'Zhou, Rui-Wei', 'Zhou, Hai-Jiao', 'He, Wen-Fei']",BMC Infect Dis,,,True
f3a5b128f4800dbbb0f49ee409acb2c0216e24dc,PMC,Estimating Sensitivity of Laboratory Testing for Influenza in Canada through Modelling,http://dx.doi.org/10.1371/journal.pone.0006681,PMC2722738,19688094,CC BY,"BACKGROUND: The weekly proportion of laboratory tests that are positive for influenza is used in public health surveillance systems to identify periods of influenza activity. We aimed to estimate the sensitivity of influenza testing in Canada based on results of a national respiratory virus surveillance system. METHODS AND FINDINGS: The weekly number of influenza-negative tests from 1999 to 2006 was modelled as a function of laboratory-confirmed positive tests for influenza, respiratory syncytial virus (RSV), adenovirus and parainfluenza viruses, seasonality, and trend using Poisson regression. Sensitivity was calculated as the number of influenza positive tests divided by the number of influenza positive tests plus the model-estimated number of false negative tests. The sensitivity of influenza testing was estimated to be 33% (95%CI 32–34%), varying from 30–40% depending on the season and region. CONCLUSIONS: The estimated sensitivity of influenza tests reported to this national laboratory surveillance system is considerably less than reported test characteristics for most laboratory tests. A number of factors may explain this difference, including sample quality and specimen procurement issues as well as test characteristics. Improved diagnosis would permit better estimation of the burden of influenza.",2009 Aug 18,"['Schanzer, Dena L.', 'Garner, Michael J.', 'Hatchette, Todd F.', 'Langley, Joanne M.', 'Aziz, Samina', 'Tam, Theresa W. S.']",PLoS One,,,True
8987e37e0598cf67e121bc72d1b95b8f1d9fde73,PMC,Rooting human parechovirus evolution in time,http://dx.doi.org/10.1186/1471-2148-9-164,PMC2723090,19604368,CC BY,"BACKGROUND: The Picornaviridae family contains a number of important pathogenic viruses, among which the recently reclassified human parechoviruses (HPeVs). These viruses are widespread and can be grouped in several types. Understanding the evolutionary history of HPeV could answer questions such as how long the circulating lineages last shared a common ancestor and how the evolution of this viral species is shaped by its population dynamics. Using both strict and relaxed clock Bayesian phylogenetics we investigated 1) the substitutions rates of the structural P1 and capsid VP1 regions and 2) evolutionary timescale of currently circulating HPeV lineages. RESULTS: Our estimates reveal that human parechoviruses exhibit high substitution rates for both structural P1 and capsid VP1 regions, respectively 2.21 × 10(-3 )(0.48 – 4.21 × 10(-3)) and 2.79 × 10(-3 )(2.05 – 3.66 × 10(-3)) substitutions per site per year. These are within the range estimated for other picornaviruses. By employing a constant population size coalescent prior, the date of the most recent common ancestor was estimated to be at around 1600 (1427–1733). In addition, by looking at the frequency of synonymous and non-synonymous substitutions within the VP1 gene we show that purifying selection constitutes the dominating evolutionary force leading to strong amino acid conservation. CONCLUSION: In conclusion, our estimates provide a timescale for the evolution of HPeVs and suggest that genetic diversity of current circulating HPeV types has arisen about 400 years ago.",2009 Jul 15,"['Faria, Nuno R', 'de Vries, Michel', 'van Hemert, Formijn J', 'Benschop, Kimberley', 'van der Hoek, Lia']",BMC Evol Biol,,,True
974dbdc07629400038b879b1f76975edfedc442d,PMC,Rooting human parechovirus evolution in time,http://dx.doi.org/10.1186/1471-2148-9-164,PMC2723090,19604368,CC BY,"BACKGROUND: The Picornaviridae family contains a number of important pathogenic viruses, among which the recently reclassified human parechoviruses (HPeVs). These viruses are widespread and can be grouped in several types. Understanding the evolutionary history of HPeV could answer questions such as how long the circulating lineages last shared a common ancestor and how the evolution of this viral species is shaped by its population dynamics. Using both strict and relaxed clock Bayesian phylogenetics we investigated 1) the substitutions rates of the structural P1 and capsid VP1 regions and 2) evolutionary timescale of currently circulating HPeV lineages. RESULTS: Our estimates reveal that human parechoviruses exhibit high substitution rates for both structural P1 and capsid VP1 regions, respectively 2.21 × 10(-3 )(0.48 – 4.21 × 10(-3)) and 2.79 × 10(-3 )(2.05 – 3.66 × 10(-3)) substitutions per site per year. These are within the range estimated for other picornaviruses. By employing a constant population size coalescent prior, the date of the most recent common ancestor was estimated to be at around 1600 (1427–1733). In addition, by looking at the frequency of synonymous and non-synonymous substitutions within the VP1 gene we show that purifying selection constitutes the dominating evolutionary force leading to strong amino acid conservation. CONCLUSION: In conclusion, our estimates provide a timescale for the evolution of HPeVs and suggest that genetic diversity of current circulating HPeV types has arisen about 400 years ago.",2009 Jul 15,"['Faria, Nuno R', 'de Vries, Michel', 'van Hemert, Formijn J', 'Benschop, Kimberley', 'van der Hoek, Lia']",BMC Evol Biol,,,False
ff4fffe02138b0b232334d997965d11fd936916b,PMC,RNA viruses in community-acquired childhood pneumonia in semi-urban Nepal; a cross-sectional study,http://dx.doi.org/10.1186/1741-7015-7-35,PMC2727531,19635124,CC BY,"BACKGROUND: Pneumonia is among the main causes of illness and death in children <5 years of age. There is a need to better describe the epidemiology of viral community-acquired pneumonia (CAP) in developing countries. METHODS: From July 2004 to June 2007, we examined nasopharyngeal aspirates (NPA) from 2,230 cases of pneumonia (World Health Organization criteria) in children 2 to 35 months old recruited in a randomized trial of zinc supplementation at a field clinic in Bhaktapur, Nepal. The specimens were examined for respiratory syncytial virus (RSV), influenza virus type A (InfA) and B (InfB), parainfluenza virus types 1, 2 and 3 (PIV1, PIV2, and PIV3), and human metapneumovirus (hMPV) using a multiplex reverse transcriptase polymerase chain reaction (PCR) assay. RESULTS: We identified 919 virus isolates in 887 (40.0%) of the 2,219 NPA specimens with a valid PCR result, of which 334 (15.1%) yielded RSV, 164 (7.4%) InfA, 129 (5.8%) PIV3, 98 (4.4%) PIV1, 93 (4.2%) hMPV, 84 (3.8%) InfB, and 17 (0.8%) PIV2. CAP occurred in an epidemic pattern with substantial temporal variation during the three years of study. The largest peaks of pneumonia occurrence coincided with peaks of RSV infection, which occurred in epidemics during the rainy season and in winter. The monthly number of RSV infections was positively correlated with relative humidity (r(s )= 0.40, P = 0.01), but not with temperature or rainfall. An hMPV epidemic occurred during one of the three winter seasons and the monthly number of hMPV cases was also associated with relative humidity (r(s )= 0.55, P = 0.0005). CONCLUSION: Respiratory RNA viruses were detected from NPA in 40% of CAP cases in our study. The most commonly isolated viruses were RSV, InfA, and PIV3. RSV infections contributed substantially to the observed CAP epidemics. The occurrence of viral CAP in this community seemed to reflect more or less overlapping micro-epidemics with several respiratory viruses, highlighting the challenges of developing and implementing effective public health control measures.",2009 Jul 27,"['Mathisen, Maria', 'Strand, Tor A', 'Sharma, Biswa N', 'Chandyo, Ram K', 'Valentiner-Branth, Palle', 'Basnet, Sudha', 'Adhikari, Ramesh K', 'Hvidsten, Dag', 'Shrestha, Prakash S', 'Sommerfelt, Halvor']",BMC Med,,,True
0953fa36903063f60627e07f7b4e07f0aec3c4d3,PMC,Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo,http://dx.doi.org/10.1186/1471-2164-10-350,PMC2728740,19650917,CC BY,"BACKGROUND: The role of type I IFNs in protecting against coronavirus (CoV) infections is not fully understood. While CoVs are poor inducers of type I IFNs in tissue culture, several studies have demonstrated the importance of the type I IFN response in controlling MHV infection in animals. The protective effectors against MHV infection are, however, still unknown. RESULTS: In order to get more insight into the antiviral gene expression induced in the brains of MHV-infected mice, we performed whole-genome expression profiling. Three different mouse strains, differing in their susceptibility to infection with MHV, were used. In BALB/c mice, which display high viral loads but are able to control the infection, 57 and 121 genes were significantly differentially expressed (≥ 1.5 fold change) upon infection at 2 and 5 days post infection, respectively. Functional association network analyses demonstrated a strong type I IFN response, with Irf1 and Irf7 as the central players. At 5 days post infection, a type II IFN response also becomes apparent. Both the type I and II IFN response, which were more pronounced in mice with a higher viral load, were not observed in 129SvEv mice, which are much less susceptible to infection with MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-), however, were not able to control the infection. Gene expression profiling of these mice identified type I IFN-independent responses to infection, with IFN-γ as the central player. As the BALB/c and the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. Many known IFN-inducible genes were detected, several of which have previously been shown to play an important protective role against virus infections. We speculate that the additional type I IFN-dependent genes that we discovered may also be important for protection against MHV infection. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Profiling of IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent responses. Overall, this study broadens our present knowledge of the type I and II IFN-mediated effector responses during CoV infection in vivo.",2009 Aug 3,"['Raaben, Matthijs', 'Groot Koerkamp, Marian JA', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,True
2850eb77e47a839ceca6b3b5d9ac3c1ed988bcad,PMC,Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo,http://dx.doi.org/10.1186/1471-2164-10-350,PMC2728740,19650917,CC BY,"BACKGROUND: The role of type I IFNs in protecting against coronavirus (CoV) infections is not fully understood. While CoVs are poor inducers of type I IFNs in tissue culture, several studies have demonstrated the importance of the type I IFN response in controlling MHV infection in animals. The protective effectors against MHV infection are, however, still unknown. RESULTS: In order to get more insight into the antiviral gene expression induced in the brains of MHV-infected mice, we performed whole-genome expression profiling. Three different mouse strains, differing in their susceptibility to infection with MHV, were used. In BALB/c mice, which display high viral loads but are able to control the infection, 57 and 121 genes were significantly differentially expressed (≥ 1.5 fold change) upon infection at 2 and 5 days post infection, respectively. Functional association network analyses demonstrated a strong type I IFN response, with Irf1 and Irf7 as the central players. At 5 days post infection, a type II IFN response also becomes apparent. Both the type I and II IFN response, which were more pronounced in mice with a higher viral load, were not observed in 129SvEv mice, which are much less susceptible to infection with MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-), however, were not able to control the infection. Gene expression profiling of these mice identified type I IFN-independent responses to infection, with IFN-γ as the central player. As the BALB/c and the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. Many known IFN-inducible genes were detected, several of which have previously been shown to play an important protective role against virus infections. We speculate that the additional type I IFN-dependent genes that we discovered may also be important for protection against MHV infection. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Profiling of IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent responses. Overall, this study broadens our present knowledge of the type I and II IFN-mediated effector responses during CoV infection in vivo.",2009 Aug 3,"['Raaben, Matthijs', 'Groot Koerkamp, Marian JA', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,False
46f10cdcf6e3db46ebfcb52f4f5cbae7a46b50f0,PMC,Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo,http://dx.doi.org/10.1186/1471-2164-10-350,PMC2728740,19650917,CC BY,"BACKGROUND: The role of type I IFNs in protecting against coronavirus (CoV) infections is not fully understood. While CoVs are poor inducers of type I IFNs in tissue culture, several studies have demonstrated the importance of the type I IFN response in controlling MHV infection in animals. The protective effectors against MHV infection are, however, still unknown. RESULTS: In order to get more insight into the antiviral gene expression induced in the brains of MHV-infected mice, we performed whole-genome expression profiling. Three different mouse strains, differing in their susceptibility to infection with MHV, were used. In BALB/c mice, which display high viral loads but are able to control the infection, 57 and 121 genes were significantly differentially expressed (≥ 1.5 fold change) upon infection at 2 and 5 days post infection, respectively. Functional association network analyses demonstrated a strong type I IFN response, with Irf1 and Irf7 as the central players. At 5 days post infection, a type II IFN response also becomes apparent. Both the type I and II IFN response, which were more pronounced in mice with a higher viral load, were not observed in 129SvEv mice, which are much less susceptible to infection with MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-), however, were not able to control the infection. Gene expression profiling of these mice identified type I IFN-independent responses to infection, with IFN-γ as the central player. As the BALB/c and the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. Many known IFN-inducible genes were detected, several of which have previously been shown to play an important protective role against virus infections. We speculate that the additional type I IFN-dependent genes that we discovered may also be important for protection against MHV infection. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Profiling of IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent responses. Overall, this study broadens our present knowledge of the type I and II IFN-mediated effector responses during CoV infection in vivo.",2009 Aug 3,"['Raaben, Matthijs', 'Groot Koerkamp, Marian JA', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,False
f26570ca165e9c5560e68b3cd897614d70401f80,PMC,Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo,http://dx.doi.org/10.1186/1471-2164-10-350,PMC2728740,19650917,CC BY,"BACKGROUND: The role of type I IFNs in protecting against coronavirus (CoV) infections is not fully understood. While CoVs are poor inducers of type I IFNs in tissue culture, several studies have demonstrated the importance of the type I IFN response in controlling MHV infection in animals. The protective effectors against MHV infection are, however, still unknown. RESULTS: In order to get more insight into the antiviral gene expression induced in the brains of MHV-infected mice, we performed whole-genome expression profiling. Three different mouse strains, differing in their susceptibility to infection with MHV, were used. In BALB/c mice, which display high viral loads but are able to control the infection, 57 and 121 genes were significantly differentially expressed (≥ 1.5 fold change) upon infection at 2 and 5 days post infection, respectively. Functional association network analyses demonstrated a strong type I IFN response, with Irf1 and Irf7 as the central players. At 5 days post infection, a type II IFN response also becomes apparent. Both the type I and II IFN response, which were more pronounced in mice with a higher viral load, were not observed in 129SvEv mice, which are much less susceptible to infection with MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-), however, were not able to control the infection. Gene expression profiling of these mice identified type I IFN-independent responses to infection, with IFN-γ as the central player. As the BALB/c and the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. Many known IFN-inducible genes were detected, several of which have previously been shown to play an important protective role against virus infections. We speculate that the additional type I IFN-dependent genes that we discovered may also be important for protection against MHV infection. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Profiling of IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent responses. Overall, this study broadens our present knowledge of the type I and II IFN-mediated effector responses during CoV infection in vivo.",2009 Aug 3,"['Raaben, Matthijs', 'Groot Koerkamp, Marian JA', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,False
d9c67ce0ec43104c6b6252fac340320752efd6e7,PMC,Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo,http://dx.doi.org/10.1186/1471-2164-10-350,PMC2728740,19650917,CC BY,"BACKGROUND: The role of type I IFNs in protecting against coronavirus (CoV) infections is not fully understood. While CoVs are poor inducers of type I IFNs in tissue culture, several studies have demonstrated the importance of the type I IFN response in controlling MHV infection in animals. The protective effectors against MHV infection are, however, still unknown. RESULTS: In order to get more insight into the antiviral gene expression induced in the brains of MHV-infected mice, we performed whole-genome expression profiling. Three different mouse strains, differing in their susceptibility to infection with MHV, were used. In BALB/c mice, which display high viral loads but are able to control the infection, 57 and 121 genes were significantly differentially expressed (≥ 1.5 fold change) upon infection at 2 and 5 days post infection, respectively. Functional association network analyses demonstrated a strong type I IFN response, with Irf1 and Irf7 as the central players. At 5 days post infection, a type II IFN response also becomes apparent. Both the type I and II IFN response, which were more pronounced in mice with a higher viral load, were not observed in 129SvEv mice, which are much less susceptible to infection with MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-), however, were not able to control the infection. Gene expression profiling of these mice identified type I IFN-independent responses to infection, with IFN-γ as the central player. As the BALB/c and the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. Many known IFN-inducible genes were detected, several of which have previously been shown to play an important protective role against virus infections. We speculate that the additional type I IFN-dependent genes that we discovered may also be important for protection against MHV infection. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Profiling of IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent responses. Overall, this study broadens our present knowledge of the type I and II IFN-mediated effector responses during CoV infection in vivo.",2009 Aug 3,"['Raaben, Matthijs', 'Groot Koerkamp, Marian JA', 'Rottier, Peter JM', 'de Haan, Cornelis AM']",BMC Genomics,,,False
44729b69ab4b60fc3e863c655d1dcc0bd02db6de,PMC,"Liquorice Health Check, Oro-Dental Implications, and a Case Report",http://dx.doi.org/10.1155/2009/170735,PMC2729489,19707475,CC BY,"Liquorice has an active substance, Glycyrrhizin which inhibits the conversion of precursor cortisol to cortisone by inhibiting the enzyme 11-betahydroxysteroid dehydrogenase. When imbibed, liquorice acts like hyperaldosteronism which presents with typical symptoms including high blood pressure, low blood potassium, and muscle pain and weakness. This article appraises physiological and pharmacological effects on health of liquorice, critiques products containing liquorice, describes a typical case report of liquorice-induced hypertension, and appraises oral effects from consumption of liquorice products.",2009 Jul 8,"Touyz, Louis Z. G.",Case Rep Med,,,True
a2759c88de238c2a28c8084c108538c8985104a4,PMC,'ONE HEALTH' and parasitology,http://dx.doi.org/10.1186/1756-3305-2-36,PMC2729733,19674442,CC BY,,2009 Aug 12,"['Kaplan, Bruce', 'Kahn, Laura H', 'Monath, Thomas P', 'Woodall, Jack']",Parasit Vectors,,,True
4424d28032612c98a50bf8654f61badc6cd22c55,PMC,Early Epidemiological Assessment of the Virulence of Emerging Infectious Diseases: A Case Study of an Influenza Pandemic,http://dx.doi.org/10.1371/journal.pone.0006852,PMC2729920,19718434,CC BY,"BACKGROUND: The case fatality ratio (CFR), the ratio of deaths from an infectious disease to the number of cases, provides an assessment of virulence. Calculation of the ratio of the cumulative number of deaths to cases during the course of an epidemic tends to result in a biased CFR. The present study develops a simple method to obtain an unbiased estimate of confirmed CFR (cCFR), using only the confirmed cases as the denominator, at an early stage of epidemic, even when there have been only a few deaths. METHODOLOGY/PRINCIPAL FINDINGS: Our method adjusts the biased cCFR by a factor of underestimation which is informed by the time from symptom onset to death. We first examine the approach by analyzing an outbreak of severe acute respiratory syndrome in Hong Kong (2003) with known unbiased cCFR estimate, and then investigate published epidemiological datasets of novel swine-origin influenza A (H1N1) virus infection in the USA and Canada (2009). Because observation of a few deaths alone does not permit estimating the distribution of the time from onset to death, the uncertainty is addressed by means of sensitivity analysis. The maximum likelihood estimate of the unbiased cCFR for influenza may lie in the range of 0.16–4.48% within the assumed parameter space for a factor of underestimation. The estimates for influenza suggest that the virulence is comparable to the early estimate in Mexico. Even when there have been no deaths, our model permits estimating a conservative upper bound of the cCFR. CONCLUSIONS: Although one has to keep in mind that the cCFR for an entire population is vulnerable to its variations among sub-populations and underdiagnosis, our method is useful for assessing virulence at the early stage of an epidemic and for informing policy makers and the public.",2009 Aug 31,"['Nishiura, Hiroshi', 'Klinkenberg, Don', 'Roberts, Mick', 'Heesterbeek, Johan A. P.']",PLoS One,,,True
3aeb264d986c987ced699cb2c711eb022b697d5a,PMC,Empirical Relationship between Intra-Purine and Intra-Pyrimidine Differences in Conserved Gene Sequences,http://dx.doi.org/10.1371/journal.pone.0006829,PMC2730015,19714250,CC BY,"DNA sequences seen in the normal character-based representation appear to have a formidable mixing of the four nucleotides without any apparent order. Nucleotide frequencies and distributions in the sequences have been studied extensively, since the simple rule given by Chargaff almost a century ago that equates the total number of purines to the pyrimidines in a duplex DNA sequence. While it is difficult to trace any relationship between the bases from studies in the character representation of a DNA sequence, graphical representations may provide a clue. These novel representations of DNA sequences have been useful in providing an overview of base distribution and composition of the sequences and providing insights into many hidden structures. We report here our observation based on a graphical representation that the intra-purine and intra-pyrimidine differences in sequences of conserved genes generally follow a quadratic distribution relationship and show that this may have arisen from mutations in the sequences over evolutionary time scales. From this hitherto undescribed relationship for the gene sequences considered in this report we hypothesize that such relationships may be characteristic of these sequences and therefore could become a barrier to large scale sequence alterations that override such characteristics, perhaps through some monitoring process inbuilt in the DNA sequences. Such relationship also raises the possibility of intron sequences playing an important role in maintaining the characteristics and could be indicative of possible intron-late phenomena.",2009 Aug 28,"Nandy, Ashesh",PLoS One,,,True
41b92c19649c6e5cd6a4e883e7edf9a43589bcdd,PMC,Identification of protein functions using a machine-learning approach based on sequence-derived properties,http://dx.doi.org/10.1186/1477-5956-7-27,PMC2731080,19664241,CC BY,"BACKGROUND: Predicting the function of an unknown protein is an essential goal in bioinformatics. Sequence similarity-based approaches are widely used for function prediction; however, they are often inadequate in the absence of similar sequences or when the sequence similarity among known protein sequences is statistically weak. This study aimed to develop an accurate prediction method for identifying protein function, irrespective of sequence and structural similarities. RESULTS: A highly accurate prediction method capable of identifying protein function, based solely on protein sequence properties, is described. This method analyses and identifies specific features of the protein sequence that are highly correlated with certain protein functions and determines the combination of protein sequence features that best characterises protein function. Thirty-three features that represent subtle differences in local regions and full regions of the protein sequences were introduced. On the basis of 484 features extracted solely from the protein sequence, models were built to predict the functions of 11 different proteins from a broad range of cellular components, molecular functions, and biological processes. The accuracy of protein function prediction using random forests with feature selection ranged from 94.23% to 100%. The local sequence information was found to have a broad range of applicability in predicting protein function. CONCLUSION: We present an accurate prediction method using a machine-learning approach based solely on protein sequence properties. The primary contribution of this paper is to propose new PNPRD features representing global and/or local differences in sequences, based on positively and/or negatively charged residues, to assist in predicting protein function. In addition, we identified a compact and useful feature subset for predicting the function of various proteins. Our results indicate that sequence-based classifiers can provide good results among a broad range of proteins, that the proposed features are useful in predicting several functions, and that the combination of our and traditional features may support the creation of a discriminative feature set for specific protein functions.",2009 Aug 9,"['Lee, Bum Ju', 'Shin, Moon Sun', 'Oh, Young Joon', 'Oh, Hae Seok', 'Ryu, Keun Ho']",Proteome Sci,,,True
d0a8b7f4cb8c1c634db8716057ae04282f65687f,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,True
e5a9130fe91644dc7bd9ef4f8d26e1d07faaca08,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,True
1a009c62e2e9971384488abc4711a6be0ef2b7c2,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
d3909545537c084455f830501a1c963e86ea7d4a,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
1d96351438bef1bb2201e1df8b0825cadde42d18,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
a15c6c90166e58a98c9d77cbc91709e106287822,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
cb96cf78ed9921212f87428bd2fe645f5f8f297e,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
bb67ff9a080a6fa65beec9c32112a630a751cf22,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
e7bc5cd2fa92efa6d0cf8b86fcc091ecf6871d6e,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
e887d0bb480276ab8336f933cf2b4fa386f40a83,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
335e0b9c181449a0f69d1d30b735ec16634c56e8,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
eb2b8dfa100caf17efae9694e4d79b529c08d625,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
af756126a149f2b19d5aeaa1c43342a1c1925722,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
10ccc558b53162f044ff17644fe0aff4871004f0,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
d23e47433d01c5edfcb3b2a3b7fd2d4be86e8486,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
64d2865dc52601e41e19d7750e1caf7f1882e4f0,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
d99d0f3c265c5bb1df189303705a530165efad3b,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
41b565d9cc80b5722f2a956316337a78156bcfe6,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
a7996cf11400a57648b6220050af479e409e90d4,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
5fbef12339e19adcc9061cf8fe0dbedb4c88f01d,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
cea8ca13bca61f7708da98cb4550976fb6a8c1b5,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
1839b151394acdff904f028d3b72ca7c055f3dd1,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
cb053f909b2187a64b73a5e7ec073801ebed4a29,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
48b442add80b6679538a8394240b016324dd8744,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
2fc6a88c3419a5ab1df09b24a094fe33e096facb,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
f169b544b6a8b585490f106910624bb1935f7afd,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
f5dd0ff704b7ebae917bb175835471471b3947e1,PMC,Evolutionarily Conserved Herpesviral Protein Interaction Networks,http://dx.doi.org/10.1371/journal.ppat.1000570,PMC2731838,19730696,CC BY,"Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.",2009 Sep 4,"['Fossum, Even', 'Friedel, Caroline C.', 'Rajagopala, Seesandra V.', 'Titz, Björn', 'Baiker, Armin', 'Schmidt, Tina', 'Kraus, Theo', 'Stellberger, Thorsten', 'Rutenberg, Christiane', 'Suthram, Silpa', 'Bandyopadhyay, Sourav', 'Rose, Dietlind', 'von Brunn, Albrecht', 'Uhlmann, Mareike', 'Zeretzke, Christine', 'Dong, Yu-An', 'Boulet, Hélène', 'Koegl, Manfred', 'Bailer, Susanne M.', 'Koszinowski, Ulrich', 'Ideker, Trey', 'Uetz, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS Pathog,,,False
faced14dbb3af799525a67f97bd6d5b904a365e3,PMC,The Application of Genomics to Emerging Zoonotic Viral Diseases,http://dx.doi.org/10.1371/journal.ppat.1000557,PMC2734983,19855817,CC BY,"Interspecies transmission of pathogens may result in the emergence of new infectious diseases in humans as well as in domestic and wild animals. Genomics tools such as high-throughput sequencing, mRNA expression profiling, and microarray-based analysis of single nucleotide polymorphisms are providing unprecedented ways to analyze the diversity of the genomes of emerging pathogens as well as the molecular basis of the host response to them. By comparing and contrasting the outcomes of an emerging infection with those of closely related pathogens in different but related host species, we can further delineate the various host pathways determining the outcome of zoonotic transmission and adaptation to the newly invaded species. The ultimate challenge is to link pathogen and host genomics data with biological outcomes of zoonotic transmission and to translate the integrated data into novel intervention strategies that eventually will allow the effective control of newly emerging infectious diseases.",2009 Oct 26,"['Haagmans, Bart L.', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.']",PLoS Pathog,,,True
fe2000f280297c40bc53ce95d703a9ca6aac19fd,PMC,Differential Regulation of Type I Interferon and Epidermal Growth Factor Pathways by a Human Respirovirus Virulence Factor,http://dx.doi.org/10.1371/journal.ppat.1000587,PMC2736567,19806178,CC BY,"A number of paramyxoviruses are responsible for acute respiratory infections in children, elderly and immuno-compromised individuals, resulting in airway inflammation and exacerbation of chronic diseases like asthma. To understand the molecular pathogenesis of these infections, we searched for cellular targets of the virulence protein C of human parainfluenza virus type 3 (hPIV3-C). We found that hPIV3-C interacts directly through its C-terminal domain with STAT1 and GRB2, whereas C proteins from measles or Nipah viruses failed to do so. Binding to STAT1 explains the previously reported capacity of hPIV3-C to block type I interferon signaling, but the interaction with GRB2 was unexpected. This adaptor protein bridges Epidermal Growth Factor (EGF) receptor to MAPK/ERK pathway, a signaling cascade recently found to be involved in airway inflammatory response. We report that either hPIV3 infection or transient expression of hPIV3-C both increase cellular response to EGF, as assessed by Elk1 transactivation and phosphorylation levels of ERK1/2, 40S ribosomal subunit protein S6 and translation initiation factor 4E (eIF4E). Furthermore, inhibition of MAPK/ERK pathway with U0126 prevented viral protein expression in infected cells. Altogether, our data provide molecular basis to explain the role of hPIV3-C as a virulence factor and determinant of pathogenesis and demonstrate that Paramyxoviridae have evolved a single virulence factor to block type I interferon signaling and to boost simultaneous cellular response to growth factors.",2009 Sep 18,"['Caignard, Grégory', 'Komarova, Anastassia V.', 'Bouraï, Mehdi', 'Mourez, Thomas', 'Jacob, Yves', 'Jones, Louis M.', 'Rozenberg, Flore', 'Vabret, Astrid', 'Freymuth, François', 'Tangy, Frédéric', 'Vidalain, Pierre-Olivier']",PLoS Pathog,,,True
4d7ed140eb8fb2b02900f7ed3ad33e99dc438989,PMC,Identification and validation of suitable endogenous reference genes for gene expression studies in human peripheral blood,http://dx.doi.org/10.1186/1755-8794-2-49,PMC2736983,19656400,CC BY,"BACKGROUND: Gene expression studies require appropriate normalization methods. One such method uses stably expressed reference genes. Since suitable reference genes appear to be unique for each tissue, we have identified an optimal set of the most stably expressed genes in human blood that can be used for normalization. METHODS: Whole-genome Affymetrix Human 2.0 Plus arrays were examined from 526 samples of males and females ages 2 to 78, including control subjects and patients with Tourette syndrome, stroke, migraine, muscular dystrophy, and autism. The top 100 most stably expressed genes with a broad range of expression levels were identified. To validate the best candidate genes, we performed quantitative RT-PCR on a subset of 10 genes (TRAP1, DECR1, FPGS, FARP1, MAPRE2, PEX16, GINS2, CRY2, CSNK1G2 and A4GALT), 4 commonly employed reference genes (GAPDH, ACTB, B2M and HMBS) and PPIB, previously reported to be stably expressed in blood. Expression stability and ranking analysis were performed using GeNorm and NormFinder algorithms. RESULTS: Reference genes were ranked based on their expression stability and the minimum number of genes needed for nomalization as calculated using GeNorm showed that the fewest, most stably expressed genes needed for acurate normalization in RNA expression studies of human whole blood is a combination of TRAP1, FPGS, DECR1 and PPIB. We confirmed the ranking of the best candidate control genes by using an alternative algorithm (NormFinder). CONCLUSION: The reference genes identified in this study are stably expressed in whole blood of humans of both genders with multiple disease conditions and ages 2 to 78. Importantly, they also have different functions within cells and thus should be expressed independently of each other. These genes should be useful as normalization genes for microarray and RT-PCR whole blood studies of human physiology, metabolism and disease.",2009 Aug 5,"['Stamova, Boryana S', 'Apperson, Michelle', 'Walker, Wynn L', 'Tian, Yingfang', 'Xu, Huichun', 'Adamczy, Peter', 'Zhan, Xinhua', 'Liu, Da-Zhi', 'Ander, Bradley P', 'Liao, Isaac H', 'Gregg, Jeffrey P', 'Turner, Renee J', 'Jickling, Glen', 'Lit, Lisa', 'Sharp, Frank R']",BMC Med Genomics,,,True
335b0a3f21f764adcbe20ff71e422d823c410098,PMC,A Serological Survey of Infectious Disease in Yellowstone National Park’s Canid Community,http://dx.doi.org/10.1371/journal.pone.0007042,PMC2738425,19756151,CC0,"BACKGROUND: Gray wolves (Canis lupus) were reintroduced into Yellowstone National Park (YNP) after a >70 year absence, and as part of recovery efforts, the population has been closely monitored. In 1999 and 2005, pup survival was significantly reduced, suggestive of disease outbreaks. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed sympatric wolf, coyote (Canis latrans), and red fox (Vulpes vulpes) serologic data from YNP, spanning 1991–2007, to identify long-term patterns of pathogen exposure, identify associated risk factors, and examine evidence for disease-induced mortality among wolves for which there were survival data. We found high, constant exposure to canine parvovirus (wolf seroprevalence: 100%; coyote: 94%), canine adenovirus-1 (wolf pups [0.5–0.9 yr]: 91%, adults [≥1 yr]: 96%; coyote juveniles [0.5–1.5 yrs]: 18%, adults [≥1.6 yrs]: 83%), and canine herpesvirus (wolf: 87%; coyote juveniles: 23%, young adults [1.6–4.9 yrs]: 51%, old adults [≥5 yrs]: 87%) suggesting that these pathogens were enzootic within YNP wolves and coyotes. An average of 50% of wolves exhibited exposure to the protozoan parasite, Neospora caninum, although individuals’ odds of exposure tended to increase with age and was temporally variable. Wolf, coyote, and fox exposure to canine distemper virus (CDV) was temporally variable, with evidence for distinct multi-host outbreaks in 1999 and 2005, and perhaps a smaller, isolated outbreak among wolves in the interior of YNP in 2002. The years of high wolf-pup mortality in 1999 and 2005 in the northern region of the park were correlated with peaks in CDV seroprevalence, suggesting that CDV contributed to the observed mortality. CONCLUSIONS/SIGNIFICANCE: Of the pathogens we examined, none appear to jeopardize the long-term population of canids in YNP. However, CDV appears capable of causing short-term population declines. Additional information on how and where CDV is maintained and the frequency with which future epizootics might be expected might be useful for future management of the Northern Rocky Mountain wolf population.",2009 Sep 16,"['Almberg, Emily S.', 'Mech, L. David', 'Smith, Douglas W.', 'Sheldon, Jennifer W.', 'Crabtree, Robert L.']",PLoS One,,,True
47266ea82145a11ad6e82db70a4d0fbd86a27cb2,PMC,SNAD: sequence name annotation-based designer,http://dx.doi.org/10.1186/1471-2105-10-251,PMC2739203,19682364,CC BY,"BACKGROUND: A growing diversity of biological data is tagged with unique identifiers (UIDs) associated with polynucleotides and proteins to ensure efficient computer-mediated data storage, maintenance, and processing. These identifiers, which are not informative for most people, are often substituted by biologically meaningful names in various presentations to facilitate utilization and dissemination of sequence-based knowledge. This substitution is commonly done manually that may be a tedious exercise prone to mistakes and omissions. RESULTS: Here we introduce SNAD (Sequence Name Annotation-based Designer) that mediates automatic conversion of sequence UIDs (associated with multiple alignment or phylogenetic tree, or supplied as plain text list) into biologically meaningful names and acronyms. This conversion is directed by precompiled or user-defined templates that exploit wealth of annotation available in cognate entries of external databases. Using examples, we demonstrate how this tool can be used to generate names for practical purposes, particularly in virology. CONCLUSION: A tool for controllable annotation-based conversion of sequence UIDs into biologically meaningful names and acronyms has been developed and placed into service, fostering links between quality of sequence annotation, and efficiency of communication and knowledge dissemination among researchers.",2009 Aug 14,"['Sidorov, Igor A', 'Reshetov, Denis A', 'Gorbalenya, Alexander E']",BMC Bioinformatics,,,True
79316a90d0cd339b0d8d40407555b253994fd833,PMC,Gene Expression Profiling in Cells with Enhanced γ-Secretase Activity,http://dx.doi.org/10.1371/journal.pone.0006952,PMC2739295,19763259,CC BY,"BACKGROUND: Processing by γ-secretase of many type-I membrane protein substrates triggers signaling cascades by releasing intracellular domains (ICDs) that, following nuclear translocation, modulate the transcription of different genes regulating a diverse array of cellular and biological processes. Because the list of γ-secretase substrates is growing quickly and this enzyme is a cancer and Alzheimer's disease therapeutic target, the mapping of γ-secretase activity susceptible gene transcription is important for sharpening our view of specific affected genes, molecular functions and biological pathways. METHODOLOGY/PRINCIPAL FINDINGS: To identify genes and molecular functions transcriptionally affected by γ-secretase activity, the cellular transcriptomes of Chinese hamster ovary (CHO) cells with enhanced and inhibited γ-secretase activity were analyzed and compared by cDNA microarray. The functional clustering by FatiGO of the 1,981 identified genes revealed over- and under-represented groups with multiple activities and functions. Single genes with the most pronounced transcriptional susceptibility to γ-secretase activity were evaluated by real-time PCR. Among the 21 validated genes, the strikingly decreased transcription of PTPRG and AMN1 and increased transcription of UPP1 potentially support data on cell cycle disturbances relevant to cancer, stem cell and neurodegenerative diseases' research. The mapping of interactions of proteins encoded by the validated genes exclusively relied on evidence-based data and revealed broad effects on Wnt pathway members, including WNT3A and DVL3. Intriguingly, the transcription of TERA, a gene of unknown function, is affected by γ-secretase activity and was significantly altered in the analyzed human Alzheimer's disease brain cortices. CONCLUSIONS/SIGNIFICANCE: Investigating the effects of γ-secretase activity on gene transcription has revealed several affected clusters of molecular functions and, more specifically, 21 genes that hold significant potential for a better understanding of the biology of γ-secretase and its roles in cancer and Alzheimer's disease pathology.",2009 Sep 18,"['Magold, Alexandra I.', 'Cacquevel, Matthias', 'Fraering, Patrick C.']",PLoS One,,,True
963285bb042097a1c7b9053b74db098d24818b25,PMC,Reverse genetic characterization of the natural genomic deletion in SARS-Coronavirus strain Frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein in-vitro and in-vivo,http://dx.doi.org/10.1186/1743-422X-6-131,PMC2739521,19698190,CC BY,"During the outbreak of SARS in 2002/3, a prototype virus was isolated from a patient in Frankfurt/Germany (strain Frankfurt-1). As opposed to all other SARS-Coronavirus strains, Frankfurt-1 has a 45-nucleotide deletion in the transmembrane domain of its ORF 7b protein. When over-expressed in HEK 293 cells, the full-length protein but not the variant with the deletion caused interferon beta induction and cleavage of procaspase 3. To study the role of ORF 7b in the context of virus replication, we cloned a full genome cDNA copy of Frankfurt-1 in a bacterial artificial chromosome downstream of a T7 RNA polymerase promoter. Transfection of capped RNA transcribed from this construct yielded infectious virus that was indistinguishable from the original virus isolate. The presumed Frankfurt-1 ancestor with an intact ORF 7b was reconstructed. In CaCo-2 and HUH7 cells, but not in Vero cells, the variant carrying the ORF 7b deletion had a replicative advantage against the parental virus (4- and 6-fold increase of virus RNA in supernatant, respectively). This effect was neither associated with changes in the induction or secretion of type I interferon, nor with altered induction of apoptosis in cell culture. However, pretreatment of cells with interferon beta caused the deleted virus to replicate to higher titers than the parental strain (3.4-fold in Vero cells, 7.9-fold in CaCo-2 cells). In Syrian Golden Hamsters inoculated intranasally with 10e4 plaque forming units of either virus, mean titers of infectious virus and viral RNA in the lungs after 24 h were increased 23- and 94.8-fold, respectively, with the deleted virus. This difference could explain earlier observations of enhanced virulence of Frankfurt-1 in Hamsters as compared to other SARS-Coronavirus reference strains and identifies the SARS-CoV 7b protein as an attenuating factor with the SARS-Coronavirus genome. Because attenuation was focused on the early phase of infection in-vivo, ORF 7b might have contributed to the delayed accumulation of virus in patients that was suggested to have limited the spread of the SARS epidemic.",2009 Aug 24,"['Pfefferle, Susanne', 'Krähling, Verena', 'Ditt, Vanessa', 'Grywna, Klaus', 'Mühlberger, Elke', 'Drosten, Christian']",Virol J,,,True
99e788920d9bc9e4792a54d4daa546045c04f9cc,PMC,Different altered stage correlative expression of high abundance acute-phase proteins in sera of patients with epithelial ovarian carcinoma,http://dx.doi.org/10.1186/1756-8722-2-37,PMC2739531,19709441,CC BY,"BACKGROUND: The general enhanced expression of α(1)-antichymotrypsin (ACT), clusterin (CLU), α(1)-antitrypsin (AAT), haptoglobin β-chain (HAP), and leucine rich glycoprotein (LRG) in the sera of patients with epithelial ovarian carcinoma (EOCa) was recently reported. In the present study, we compared the expression of the serum acute-phase proteins (APPs) in the patients according to their stages of cancer. RESULTS: Different altered stage correlative expression of the high abundance serum APPs was demonstrated in sera of the patients studied. While the expression of ACT, HAP and AAT appeared to demonstrate positive correlation with the three initial stages of the cancer, inverse correlation was apparently detected in the expression of LRG and CLU. For patients who were diagnosed with stage IV of the cancer, expression of the serum APPs did not conform to the altered progression changes. CONCLUSION: Our results highlight the potential prognostic significance of selective high abundance serum APPs in patients with EOCa.",2009 Aug 27,"['Chen, Yeng', 'Lim, Boon-Kiong', 'Hashim, Onn H']",J Hematol Oncol,,,True
f06b500cbbffe7641b716dbbb90f0d40ed7839d6,PMC,Bayesian Phylogeography Finds Its Roots,http://dx.doi.org/10.1371/journal.pcbi.1000520,PMC2740835,19779555,CC BY,"As a key factor in endemic and epidemic dynamics, the geographical distribution of viruses has been frequently interpreted in the light of their genetic histories. Unfortunately, inference of historical dispersal or migration patterns of viruses has mainly been restricted to model-free heuristic approaches that provide little insight into the temporal setting of the spatial dynamics. The introduction of probabilistic models of evolution, however, offers unique opportunities to engage in this statistical endeavor. Here we introduce a Bayesian framework for inference, visualization and hypothesis testing of phylogeographic history. By implementing character mapping in a Bayesian software that samples time-scaled phylogenies, we enable the reconstruction of timed viral dispersal patterns while accommodating phylogenetic uncertainty. Standard Markov model inference is extended with a stochastic search variable selection procedure that identifies the parsimonious descriptions of the diffusion process. In addition, we propose priors that can incorporate geographical sampling distributions or characterize alternative hypotheses about the spatial dynamics. To visualize the spatial and temporal information, we summarize inferences using virtual globe software. We describe how Bayesian phylogeography compares with previous parsimony analysis in the investigation of the influenza A H5N1 origin and H5N1 epidemiological linkage among sampling localities. Analysis of rabies in West African dog populations reveals how virus diffusion may enable endemic maintenance through continuous epidemic cycles. From these analyses, we conclude that our phylogeographic framework will make an important asset in molecular epidemiology that can be easily generalized to infer biogeogeography from genetic data for many organisms.",2009 Sep 25,"['Lemey, Philippe', 'Rambaut, Andrew', 'Drummond, Alexei J.', 'Suchard, Marc A.']",PLoS Comput Biol,,,True
d582ab2a736fc7555df7ad6512afbdcd74056201,PMC,Increased ATP generation in the host cell is required for efficient vaccinia virus production,http://dx.doi.org/10.1186/1423-0127-16-80,PMC2741444,19725950,CC BY,"To search for cellular genes up-regulated by vaccinia virus (VV) infection, differential display-reverse transcription-polymerase chain reaction (ddRT-PCR) assays were used to examine the expression of mRNAs from mock-infected and VV-infected HeLa cells. Two mitochondrial genes for proteins that are part of the electron transport chain that generates ATP, ND4 and CO II, were up-regulated after VV infection. Up-regulation of ND4 level by VV infection was confirmed by Western blotting analysis. Up-regulation of ND4 was reduced by the MAPK inhibitor, apigenin, which has been demonstrated elsewhere to inhibit VV replication. The induction of ND4 expression occurred after viral DNA replication since ara C, an inhibitor of poxviral DNA replication, could block this induction. ATP production was increased in the host cells after VV infection. Moreover, 4.5 μM oligomycin, an inhibitor of ATP production, reduced the ATP level 13 hr after virus infection to that of mock-infected cells and inhibited viral protein expression and virus production, suggesting that increased ATP production is required for efficient VV production. Our results further suggest that induction of ND4 expression is through a Bcl-2 independent pathway.",2009 Sep 2,"['Chang, Chia-Wei', 'Li, Hui-Chun', 'Hsu, Che-Fang', 'Chang, Chiao-Yen', 'Lo, Shih-Yen']",J Biomed Sci,,,True
b7e7ff011d768680bee745105bd24389068a5a1f,PMC,Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways,http://dx.doi.org/10.1371/journal.ppat.1000594,PMC2741593,19763269,CC0,"One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.",2009 Sep 18,"['Rong, Rong', 'Li, Bing', 'Lynch, Rebecca M.', 'Haaland, Richard E.', 'Murphy, Megan K.', 'Mulenga, Joseph', 'Allen, Susan A.', 'Pinter, Abraham', 'Shaw, George M.', 'Hunter, Eric', 'Robinson, James E.', 'Gnanakaran, S.', 'Derdeyn, Cynthia A.']",PLoS Pathog,,,True
fc473cd495077e770af4646766ab52ec5f69ea5c,PMC,Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways,http://dx.doi.org/10.1371/journal.ppat.1000594,PMC2741593,19763269,CC0,"One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.",2009 Sep 18,"['Rong, Rong', 'Li, Bing', 'Lynch, Rebecca M.', 'Haaland, Richard E.', 'Murphy, Megan K.', 'Mulenga, Joseph', 'Allen, Susan A.', 'Pinter, Abraham', 'Shaw, George M.', 'Hunter, Eric', 'Robinson, James E.', 'Gnanakaran, S.', 'Derdeyn, Cynthia A.']",PLoS Pathog,,,False
660a2426bce5b77f9977be2c5149b548523d601b,PMC,Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways,http://dx.doi.org/10.1371/journal.ppat.1000594,PMC2741593,19763269,CC0,"One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.",2009 Sep 18,"['Rong, Rong', 'Li, Bing', 'Lynch, Rebecca M.', 'Haaland, Richard E.', 'Murphy, Megan K.', 'Mulenga, Joseph', 'Allen, Susan A.', 'Pinter, Abraham', 'Shaw, George M.', 'Hunter, Eric', 'Robinson, James E.', 'Gnanakaran, S.', 'Derdeyn, Cynthia A.']",PLoS Pathog,,,False
4204ef31e94508ac502575600aa56747d7674adb,PMC,Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways,http://dx.doi.org/10.1371/journal.ppat.1000594,PMC2741593,19763269,CC0,"One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.",2009 Sep 18,"['Rong, Rong', 'Li, Bing', 'Lynch, Rebecca M.', 'Haaland, Richard E.', 'Murphy, Megan K.', 'Mulenga, Joseph', 'Allen, Susan A.', 'Pinter, Abraham', 'Shaw, George M.', 'Hunter, Eric', 'Robinson, James E.', 'Gnanakaran, S.', 'Derdeyn, Cynthia A.']",PLoS Pathog,,,False
f117152847c55af7a94ce6953a96e7d3f056c216,PMC,Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways,http://dx.doi.org/10.1371/journal.ppat.1000594,PMC2741593,19763269,CC0,"One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.",2009 Sep 18,"['Rong, Rong', 'Li, Bing', 'Lynch, Rebecca M.', 'Haaland, Richard E.', 'Murphy, Megan K.', 'Mulenga, Joseph', 'Allen, Susan A.', 'Pinter, Abraham', 'Shaw, George M.', 'Hunter, Eric', 'Robinson, James E.', 'Gnanakaran, S.', 'Derdeyn, Cynthia A.']",PLoS Pathog,,,False
4f586b0b5a0c46d2b3e3079ed5d4f15ddbc44496,PMC,Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways,http://dx.doi.org/10.1371/journal.ppat.1000594,PMC2741593,19763269,CC0,"One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.",2009 Sep 18,"['Rong, Rong', 'Li, Bing', 'Lynch, Rebecca M.', 'Haaland, Richard E.', 'Murphy, Megan K.', 'Mulenga, Joseph', 'Allen, Susan A.', 'Pinter, Abraham', 'Shaw, George M.', 'Hunter, Eric', 'Robinson, James E.', 'Gnanakaran, S.', 'Derdeyn, Cynthia A.']",PLoS Pathog,,,False
f631f484f2f69474e722bfbe18a51b3957ff1047,PMC,Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways,http://dx.doi.org/10.1371/journal.ppat.1000594,PMC2741593,19763269,CC0,"One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.",2009 Sep 18,"['Rong, Rong', 'Li, Bing', 'Lynch, Rebecca M.', 'Haaland, Richard E.', 'Murphy, Megan K.', 'Mulenga, Joseph', 'Allen, Susan A.', 'Pinter, Abraham', 'Shaw, George M.', 'Hunter, Eric', 'Robinson, James E.', 'Gnanakaran, S.', 'Derdeyn, Cynthia A.']",PLoS Pathog,,,False
178363fb71ad0ae91e621e6e51fc03bb521f5695,PMC,Crystal Structure of the N-Acetylmannosamine Kinase Domain of GNE,http://dx.doi.org/10.1371/journal.pone.0007165,PMC2742894,19841673,CC BY,"BACKGROUND: UDP-GlcNAc 2-epimerase/ManNAc 6-kinase, GNE, is a bi-functional enzyme that plays a key role in sialic acid biosynthesis. Mutations of the GNE protein cause sialurea or autosomal recessive inclusion body myopathy/Nonaka myopathy. GNE is the only human protein that contains a kinase domain belonging to the ROK (repressor, ORF, kinase) family. PRINCIPAL FINDINGS: We solved the structure of the GNE kinase domain in the ligand-free state. The protein exists predominantly as a dimer in solution, with small populations of monomer and higher-order oligomer in equilibrium with the dimer. Crystal packing analysis reveals the existence of a crystallographic hexamer, and that the kinase domain dimerizes through the C-lobe subdomain. Mapping of disease-related missense mutations onto the kinase domain structure revealed that the mutation sites could be classified into four different groups based on the location – dimer interface, interlobar helices, protein surface, or within other secondary structural elements. CONCLUSIONS: The crystal structure of the kinase domain of GNE provides a structural basis for understanding disease-causing mutations and a model of hexameric wild type full length enzyme. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.",2009 Oct 20,"['Tong, Yufeng', 'Tempel, Wolfram', 'Nedyalkova, Lyudmila', 'MacKenzie, Farrell', 'Park, Hee-Won']",PLoS One,,,True
7f37a4d0fbe40b259fc13a04449eec3983d45c4e,PMC,Crystal Structure of the N-Acetylmannosamine Kinase Domain of GNE,http://dx.doi.org/10.1371/journal.pone.0007165,PMC2742894,19841673,CC BY,"BACKGROUND: UDP-GlcNAc 2-epimerase/ManNAc 6-kinase, GNE, is a bi-functional enzyme that plays a key role in sialic acid biosynthesis. Mutations of the GNE protein cause sialurea or autosomal recessive inclusion body myopathy/Nonaka myopathy. GNE is the only human protein that contains a kinase domain belonging to the ROK (repressor, ORF, kinase) family. PRINCIPAL FINDINGS: We solved the structure of the GNE kinase domain in the ligand-free state. The protein exists predominantly as a dimer in solution, with small populations of monomer and higher-order oligomer in equilibrium with the dimer. Crystal packing analysis reveals the existence of a crystallographic hexamer, and that the kinase domain dimerizes through the C-lobe subdomain. Mapping of disease-related missense mutations onto the kinase domain structure revealed that the mutation sites could be classified into four different groups based on the location – dimer interface, interlobar helices, protein surface, or within other secondary structural elements. CONCLUSIONS: The crystal structure of the kinase domain of GNE provides a structural basis for understanding disease-causing mutations and a model of hexameric wild type full length enzyme. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.",2009 Oct 20,"['Tong, Yufeng', 'Tempel, Wolfram', 'Nedyalkova, Lyudmila', 'MacKenzie, Farrell', 'Park, Hee-Won']",PLoS One,,,False
5aa7bb757f909abc71347a4add89dcdde3f9b7b1,PMC,Inducible Bronchus-Associated Lymphoid Tissue Elicited by a Protein Cage Nanoparticle Enhances Protection in Mice against Diverse Respiratory Viruses,http://dx.doi.org/10.1371/journal.pone.0007142,PMC2743193,19774076,CC BY,"BACKGROUND: Destruction of the architectural and subsequently the functional integrity of the lung following pulmonary viral infections is attributable to both the extent of pathogen replication and to the host-generated inflammation associated with the recruitment of immune responses. The presence of antigenically disparate pulmonary viruses and the emergence of novel viruses assures the recurrence of lung damage with infection and resolution of each primary viral infection. Thus, there is a need to develop safe broad spectrum immunoprophylactic strategies capable of enhancing protective immune responses in the lung but which limits immune-mediated lung damage. The immunoprophylactic strategy described here utilizes a protein cage nanoparticle (PCN) to significantly accelerate clearance of diverse respiratory viruses after primary infection and also results in a host immune response that causes less lung damage. METHODOLOGY/PRINCIPAL FINDINGS: Mice pre-treated with PCN, independent of any specific viral antigens, were protected against both sub-lethal and lethal doses of two different influenza viruses, a mouse-adapted SARS-coronavirus, or mouse pneumovirus. Treatment with PCN significantly increased survival and was marked by enhanced viral clearance, accelerated induction of viral-specific antibody production, and significant decreases in morbidity and lung damage. The enhanced protection appears to be dependent upon the prior development of inducible bronchus-associated lymphoid tissue (iBALT) in the lung in response to the PCN treatment and to be mediated through CD4+ T cell and B cell dependent mechanisms. CONCLUSIONS/SIGNIFICANCE: The immunoprophylactic strategy described utilizes an infection-independent induction of naturally occurring iBALT prior to infection by a pulmonary viral pathogen. This strategy non-specifically enhances primary immunity to respiratory viruses and is not restricted by the antigen specificities inherent in typical vaccination strategies. PCN treatment is asymptomatic in its application and importantly, ameliorates the damaging inflammation normally associated with the recruitment of immune responses into the lung.",2009 Sep 23,"['Wiley, James A.', 'Richert, Laura E.', 'Swain, Steve D.', 'Harmsen, Ann', 'Barnard, Dale L.', 'Randall, Troy D.', 'Jutila, Mark', 'Douglas, Trevor', 'Broomell, Chris', 'Young, Mark', 'Harmsen, Allen']",PLoS One,,,True
f43e2e8087f69f1fd27714d2f600d66321d8f0e9,PMC,"Optimism/pessimism and health-related quality of life during pregnancy across three continents: a matched cohort study in China, Ghana, and the United States",http://dx.doi.org/10.1186/1471-2393-9-39,PMC2744663,19723332,CC BY,"BACKGROUND: Little is known about how optimism/pessimism and health-related quality of life compare across cultures. METHODS: Three samples of pregnant women in their final trimester were recruited from China, Ghana, and the United States (U.S.). Participants completed a survey that included the Life Orientation Test - Revised (LOT-R, an optimism/pessimism measure), the Short Form 12 (SF-12, a quality of life measure), and questions addressing health and demographic factors. A three-country set was created for analysis by matching women on age, gestational age at enrollment, and number of previous pregnancies. Anovas with post-hoc pairwise comparisons were used to compare results across the cohorts. Multivariate regression analysis was used to create a model to identify those variables most strongly associated with optimism/pessimism. RESULTS: LOT-R scores varied significantly across cultures in these samples, with Ghanaian pregnant women being the most optimistic and least pessimistic and Chinese pregnant women being the least optimistic overall and the least pessimistic in subscale analysis. Four key variables predicted approximately 20% of the variance in overall optimism scores: country of origin (p = .006), working for money (p = .05); level of education (p = .002), and ever being treated for emotional issues with medication (p < .001). Quality of life scores also varied by country in these samples, with the most pronounced difference occurring in the vitality measure. U.S. pregnant women reported far lower vitality scores than both Chinese and Ghanaian pregnant women in our sample. CONCLUSION: This research raises important questions regarding what it is about country of origin that so strongly influences optimism/pessimism among pregnant women. Further research is warranted exploring underlying conceptualization of optimism/pessimism and health related quality of life across countries.",2009 Sep 1,"['Moyer, Cheryl A', 'Yang, Huixia', 'Kwawukume, Yao', 'Gupta, Anu', 'Zhu, YuChun', 'Koranteng, Isaac', 'Elsayed, Yasmin', 'Wei, YuMei', 'Greene, Jonathan', 'Calhoun, Cecilia', 'Ekpo, Geraldine', 'Beems, Megan', 'Ryan, Megan', 'Adanu, Richard', 'Anderson, Frank']",BMC Pregnancy Childbirth,,,True
589bb887a113e04b714724a7ec3589037449dc39,PMC,RNase L Mediated Protection from Virus Induced Demyelination,http://dx.doi.org/10.1371/journal.ppat.1000602,PMC2745574,19798426,CC BY,"IFN-α/β plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-α/β dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-α/β pathway through RNA degradation intermediates. Infection of RNase L deficient (RL(−/−)) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-α/β expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL(−/−) mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-α/β mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination.",2009 Oct 2,"['Ireland, Derek D. C.', 'Stohlman, Stephen A.', 'Hinton, David R.', 'Kapil, Parul', 'Silverman, Robert H.', 'Atkinson, Roscoe A.', 'Bergmann, Cornelia C.']",PLoS Pathog,,,True
561bde3336a2cd2006251effb54e5428c4edf3b9,PMC,Systems Integration of Biodefense Omics Data for Analysis of Pathogen-Host Interactions and Identification of Potential Targets,http://dx.doi.org/10.1371/journal.pone.0007162,PMC2745575,19779614,CC BY,"The NIAID (National Institute for Allergy and Infectious Diseases) Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents. The Biodefense Resource Center (www.proteomicsresource.org) has developed a bioinformatics framework, employing a protein-centric approach to integrate and support mining and analysis of the large and heterogeneous data. Underlying this approach is a data warehouse with comprehensive protein + gene identifier and name mappings and annotations extracted from over 100 molecular databases. Value-added annotations are provided for key proteins from experimental findings using controlled vocabulary. The availability of pathogen and host omics data in an integrated framework allows global analysis of the data and comparisons across different experiments and organisms, as illustrated in several case studies presented here. (1) The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells) infected by different bacterial (Bacillus anthracis and Salmonella typhimurium) and viral (orthopox) pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. (2) The analysis of a vaccinia-human protein interaction network supplemented with protein accumulation levels led to the identification of human Keratin, type II cytoskeletal 4 protein as a potential therapeutic target. (3) Comparison of complete genomes from pathogenic variants coupled with experimental information on complete proteomes allowed the identification and prioritization of ten potential diagnostic targets from Bacillus anthracis. The integrative analysis across data sets from multiple centers can reveal potential functional significance and hidden relationships between pathogen and host proteins, thereby providing a systems approach to basic understanding of pathogenicity and target identification.",2009 Sep 25,"['McGarvey, Peter B.', 'Huang, Hongzhan', 'Mazumder, Raja', 'Zhang, Jian', 'Chen, Yongxing', 'Zhang, Chengdong', 'Cammer, Stephen', 'Will, Rebecca', 'Odle, Margie', 'Sobral, Bruno', 'Moore, Margaret', 'Wu, Cathy H.']",PLoS One,,,True
c6fde7aab8fedbe212cac83d89064d4fb74089b9,PMC,Emerging Technologies for the Detection of Rabies Virus: Challenges and Hopes in the 21st Century,http://dx.doi.org/10.1371/journal.pntd.0000530,PMC2745658,19787037,CC BY,"The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries. Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable. These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied. In the course of the past three decades, the application of molecular biology has aided in the development of tests that result in a more rapid detection of rabies virus. These tests enable viral strain identification from clinical specimens. Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis. Indeed the challenges in the 21st century for the development of rabies diagnostics are not of a technical nature; these tests are available now. The challenges in the 21st century for diagnostic test developers are two-fold: firstly, to achieve internationally accepted validation of a test that will then lead to its acceptance by organisations globally. Secondly, the areas of the world where such tests are needed are mainly in developing regions where financial and logistical barriers prevent their implementation. Although developing countries with a poor healthcare infrastructure recognise that molecular-based diagnostic assays will be unaffordable for routine use, the cost/benefit ratio should still be measured. Adoption of rapid and affordable rabies diagnostic tests for use in developing countries highlights the importance of sharing and transferring technology through laboratory twinning between the developed and the developing countries. Importantly for developing countries, the benefit of molecular methods as tools is the capability for a differential diagnosis of human diseases that present with similar clinical symptoms. Antemortem testing for human rabies is now possible using molecular techniques. These barriers are not insurmountable and it is our expectation that if such tests are accepted and implemented where they are most needed, they will provide substantial improvements for rabies diagnosis and surveillance. The advent of molecular biology and new technological initiatives that combine advances in biology with other disciplines will support the development of techniques capable of high throughput testing with a low turnaround time for rabies diagnosis.",2009 Sep 29,"['Fooks, Anthony R.', 'Johnson, Nicholas', 'Freuling, Conrad M.', 'Wakeley, Philip R.', 'Banyard, Ashley C.', 'McElhinney, Lorraine M.', 'Marston, Denise A.', 'Dastjerdi, Akbar', 'Wright, Edward', 'Weiss, Robin A.', 'Müller, Thomas']",PLoS Negl Trop Dis,,,True
c9df58c92109a1057c10b24867cb3566ffb46408,PMC,Prospects for control of emerging infectious diseases with plasmid DNA vaccines,http://dx.doi.org/10.1186/1476-8518-7-3,PMC2746192,19735569,CC BY,"Experiments almost 20 years ago demonstrated that injections of a sequence of DNA encoding part of a pathogen could stimulate immunity. It was soon realized that ""DNA vaccination"" had numerous potential advantages over conventional vaccine approaches including inherent safety and a more rapid production time. These and other attributes make DNA vaccines ideal for development against emerging pathogens. Recent advances in optimizing various aspects of DNA vaccination have accelerated this approach from concept to reality in contemporary human trials. Although not yet licensed for human use, several DNA vaccines have now been approved for animal health indications. The rapid manufacturing capabilities of DNA vaccines may be particularly important for emerging infectious diseases including the current novel H1N1 Influenza A pandemic, where pre-existing immunity is limited. Because of recent advances in DNA vaccination, this approach has the potential to be a powerful new weapon in protecting against emerging and potentially pandemic human pathogens.",2009 Sep 7,"Moss, Ronald B",J Immune Based Ther Vaccines,,,True
de4ab44a9e3ff11c0f831a0ab5a421191c78c6dc,PMC,Nationwide epidemiological study of severe gallstone disease in Taiwan,http://dx.doi.org/10.1186/1471-230X-9-63,PMC2746226,19698126,CC BY,"BACKGROUND: Our study aimed to assess the nationwide trends in the incidence of severe gallstone disease in Taiwan among adults aged ≥20. METHODS: A retrospective longitudinal study was conducted using Taiwan National Health Insurance Research Database collected during 1997–2005. Patients with incident severe gallstone disease (acute cholecystitis, biliary pancreatitis, acute cholangitis) and gallstone-related procedures (elective and non-elective cholecystectomy, endoscopic retrograde cholangiopancreatography [ERCP]) that led to hospital admission were identified using ICD-9-CM diagnostic and procedure codes. Annual incidence rates of gallstone-related complications and procedures were calculated and their 95% confidence intervals (CI) were estimated assuming a Poisson distribution. RESULTS: The hospital admission rate for severe gallstone disease increased with advancing age and the age-standardized rate (95% CI) per 1000 population was 0.60 (0.59–0.60) for men and 0.59 (0.59–0.60) for women. Men had a higher rate of acute cholecystitis, probably due to the substantially lower rate of elective cholecystectomy among men than women. For those aged 20–39, hospital admissions for all gallstone-related complications and procedures increased significantly. For those aged ≥60, incidences of biliary pancreatitis, acute cholangitis, and hospital admission for gallstone receiving ERCP increased significantly without substantial change in the incidence of acute cholecystitis and despite a decreased rate of elective cholecystectomy. CONCLUSION: This population-based study found a substantial increase in the rate of admission for severe gallstone disease among those aged 20–39. Concurrently, the incidences of biliary pancreatitis and acute cholangitis have risen among those aged ≥60.",2009 Aug 22,"['Huang, John', 'Chang, Chia-Hsuin', 'Wang, Juin-Ling', 'Kuo, Hsu-Ko', 'Lin, Jou-Wei', 'Shau, Wen-Yi', 'Lee, Po-Huang']",BMC Gastroenterol,,,True
2a8339ac2c0891d5113f221ebd214f2b1d903d38,PMC,High quality protein microarray using in situ protein purification,http://dx.doi.org/10.1186/1472-6750-9-72,PMC2746808,19698181,CC BY,"BACKGROUND: In the postgenomic era, high throughput protein expression and protein microarray technologies have progressed markedly permitting screening of therapeutic reagents and discovery of novel protein functions. Hexa-histidine is one of the most commonly used fusion tags for protein expression due to its small size and convenient purification via immobilized metal ion affinity chromatography (IMAC). This purification process has been adapted to the protein microarray format, but the quality of in situ His-tagged protein purification on slides has not been systematically evaluated. We established methods to determine the level of purification of such proteins on metal chelate-modified slide surfaces. Optimized in situ purification of His-tagged recombinant proteins has the potential to become the new gold standard for cost-effective generation of high-quality and high-density protein microarrays. RESULTS: Two slide surfaces were examined, chelated Cu(2+ )slides suspended on a polyethylene glycol (PEG) coating and chelated Ni(2+ )slides immobilized on a support without PEG coating. Using PEG-coated chelated Cu(2+ )slides, consistently higher purities of recombinant proteins were measured. An optimized wash buffer (PBST) composed of 10 mM phosphate buffer, 2.7 mM KCl, 140 mM NaCl and 0.05% Tween 20, pH 7.4, further improved protein purity levels. Using Escherichia coli cell lysates expressing 90 recombinant Streptococcus pneumoniae proteins, 73 proteins were successfully immobilized, and 66 proteins were in situ purified with greater than 90% purity. We identified several antigens among the in situ-purified proteins via assays with anti-S. pneumoniae rabbit antibodies and a human patient antiserum, as a demonstration project of large scale microarray-based immunoproteomics profiling. The methodology is compatible with higher throughput formats of in vivo protein expression, eliminates the need for resin-based purification and circumvents protein solubility and denaturation problems caused by buffer exchange steps and freeze-thaw cycles, which are associated with resin-based purification, intermittent protein storage and deposition on microarrays. CONCLUSION: An optimized platform for in situ protein purification on microarray slides using His-tagged recombinant proteins is a desirable tool for the screening of novel protein functions and protein-protein interactions. In the context of immunoproteomics, such protein microarrays are complimentary to approaches using non-recombinant methods to discover and characterize bacterial antigens.",2009 Aug 23,"['Kwon, Keehwan', 'Grose, Carissa', 'Pieper, Rembert', 'Pandya, Gagan A', 'Fleischmann, Robert D', 'Peterson, Scott N']",BMC Biotechnol,,,True
d0d3db0b7401dbecdab05576f43883e00fbd41db,PMC,High quality protein microarray using in situ protein purification,http://dx.doi.org/10.1186/1472-6750-9-72,PMC2746808,19698181,CC BY,"BACKGROUND: In the postgenomic era, high throughput protein expression and protein microarray technologies have progressed markedly permitting screening of therapeutic reagents and discovery of novel protein functions. Hexa-histidine is one of the most commonly used fusion tags for protein expression due to its small size and convenient purification via immobilized metal ion affinity chromatography (IMAC). This purification process has been adapted to the protein microarray format, but the quality of in situ His-tagged protein purification on slides has not been systematically evaluated. We established methods to determine the level of purification of such proteins on metal chelate-modified slide surfaces. Optimized in situ purification of His-tagged recombinant proteins has the potential to become the new gold standard for cost-effective generation of high-quality and high-density protein microarrays. RESULTS: Two slide surfaces were examined, chelated Cu(2+ )slides suspended on a polyethylene glycol (PEG) coating and chelated Ni(2+ )slides immobilized on a support without PEG coating. Using PEG-coated chelated Cu(2+ )slides, consistently higher purities of recombinant proteins were measured. An optimized wash buffer (PBST) composed of 10 mM phosphate buffer, 2.7 mM KCl, 140 mM NaCl and 0.05% Tween 20, pH 7.4, further improved protein purity levels. Using Escherichia coli cell lysates expressing 90 recombinant Streptococcus pneumoniae proteins, 73 proteins were successfully immobilized, and 66 proteins were in situ purified with greater than 90% purity. We identified several antigens among the in situ-purified proteins via assays with anti-S. pneumoniae rabbit antibodies and a human patient antiserum, as a demonstration project of large scale microarray-based immunoproteomics profiling. The methodology is compatible with higher throughput formats of in vivo protein expression, eliminates the need for resin-based purification and circumvents protein solubility and denaturation problems caused by buffer exchange steps and freeze-thaw cycles, which are associated with resin-based purification, intermittent protein storage and deposition on microarrays. CONCLUSION: An optimized platform for in situ protein purification on microarray slides using His-tagged recombinant proteins is a desirable tool for the screening of novel protein functions and protein-protein interactions. In the context of immunoproteomics, such protein microarrays are complimentary to approaches using non-recombinant methods to discover and characterize bacterial antigens.",2009 Aug 23,"['Kwon, Keehwan', 'Grose, Carissa', 'Pieper, Rembert', 'Pandya, Gagan A', 'Fleischmann, Robert D', 'Peterson, Scott N']",BMC Biotechnol,,,False
c8eb13b64a5392a43ac16027e68b30573a9d0df0,PMC,Validation of a short form Wisconsin Upper Respiratory Symptom Survey (WURSS-21),http://dx.doi.org/10.1186/1477-7525-7-76,PMC2748069,19674476,CC BY,"BACKGROUND: The Wisconsin Upper Respiratory Symptom Survey (WURSS) is an illness-specific health-related quality-of-life questionnaire outcomes instrument. OBJECTIVES: Research questions were: 1) How well does the WURSS-21 assess the symptoms and functional impairments associated with common cold? 2) How well can this instrument measure change over time (responsiveness)? 3) What is the minimal important difference (MID) that can be detected by the WURSS-21? 4) What are the descriptive statistics for area under the time severity curve (AUC)? 5) What sample sizes would trials require to detect MID or AUC criteria? 6) What does factor analysis tell us about the underlying dimensional structure of the common cold? 7) How reliable are items, domains, and summary scores represented in WURSS? 8) For each of these considerations, how well does the WURSS-21 compare to the WURSS-44, Jackson, and SF-8? STUDY DESIGN AND SETTING: People with Jackson-defined colds were recruited from the community in and around Madison, Wisconsin. Participants were enrolled within 48 hours of first cold symptom and monitored for up to 14 days of illness. Half the sample filled out the WURSS-21 in the morning and the WURSS-44 in the evening, with the other half reversing the daily order. External comparators were the SF-8, a 24-hour recall general health measure yielding separate physical and mental health scores, and the eight-item Jackson cold index, which assesses symptoms, but not functional impairment or quality of life. RESULTS: In all, 230 participants were monitored for 2,457 person-days. Participants were aged 14 to 83 years (mean 34.1, SD 13.6), majority female (66.5%), mostly white (86.0%), and represented substantive education and income diversity. WURSS-21 items demonstrated similar performance when embedded within the WURSS-44 or in the stand-alone WURSS-21. Minimal important difference (MID) and Guyatt's responsiveness index were 10.3, 0.71 for the WURSS-21 and 18.5, 0.75 for the WURSS-44. Factorial analysis suggested an eight dimension structure for the WURSS-44 and a three dimension structure for the WURSS-21, with composite reliability coefficients ranging from 0.87 to 0.97, and Cronbach's alpha ranging from 0.76 to 0.96. Both WURSS versions correlated significantly with the Jackson scale (W-21 R = 0.85; W-44 R = 0.88), with the SF-8 physical health (W-21 R = -0.79; W-44 R = -0.80) and SF-8 mental health (W-21 R = -0.55; W-44 R = -0.60). CONCLUSION: The WURSS-44 and WURSS-21 perform well as illness-specific quality-of-life evaluative outcome instruments. Construct validity is supported by the data presented here. While the WURSS-44 covers more symptoms, the WURSS-21 exhibits similar performance in terms of reliability, responsiveness, importance-to-patients, and convergence with other measures.",2009 Aug 12,"['Barrett, Bruce', 'Brown, Roger L', 'Mundt, Marlon P', 'Thomas, Gay R', 'Barlow, Shari K', 'Highstrom, Alex D', 'Bahrainian, Mozhdeh']",Health Qual Life Outcomes,,,True
38f12e7be8d0f29aabe77ac96fa19d62407c0898,PMC,A case for a CUG-initiated coding sequence overlapping torovirus ORF1a and encoding a novel 30 kDa product,http://dx.doi.org/10.1186/1743-422X-6-136,PMC2749830,19737402,CC BY,"The genus Torovirus (order Nidovirales) includes a number of species that infect livestock. These viruses have a linear positive-sense ssRNA genome of ~25-30 kb, encoding a large polyprotein that is expressed from the genomic RNA, and several additional proteins expressed from a nested set of 3'-coterminal subgenomic RNAs. In this brief report, we describe the bioinformatic discovery of a new, apparently coding, ORF that overlaps the 5' end of the polyprotein coding sequence, ORF1a, in the +2 reading frame. The new ORF has a strong coding signature and, in fact, is more conserved at the amino acid level than the overlapping region of ORF1a. We propose that the new ORF utilizes a non-AUG initiation codon - namely a conserved CUG codon in a strong Kozak context - upstream of the ORF1a AUG initiation codon, resulting in a novel 258 amino acid protein, dubbed '30K'.",2009 Sep 8,"['Firth, Andrew E', 'Atkins, John F']",Virol J,,,True
3bac7494aeafbb2f2cff25690dac67e99c120029,PMC,Development of a fluorescent quantitative real-time polymerase chain reaction assay for the detection of Goose parvovirus in vivo,http://dx.doi.org/10.1186/1743-422X-6-142,PMC2751755,19754946,CC BY,"BACKGROUND: Goose parvovirus (GPV) is a Dependovirus associated with latent infection and mortality in geese. Currently, it severely affects geese production worldwide. The objective of this study was to develop a fluorescent quantitative real-time polymerase chain reaction (PCR) (FQ-PCR) assay for fast and accurate quantification of GPV DNA in infected goslings, which can aid in the understanding of the regular distribution pattern and the nosogenesis of GPV in vivo. RESULTS: The detection limit of the assay was 2.8 × 10(1 )standard DNA copies, with a sensitivity of 3 logs higher than that of the conventional gel-based PCR assay targeting the same gene. The real-time PCR was reproducible, as shown by satisfactory low intraassay and interassay coefficients of variation. CONCLUSION: The high sensitivity, specificity, simplicity, and reproducibility of the GPV fluorogenic PCR assay, combined with a high throughput, make this method suitable for a broad spectrum of GPV etiology-related applications.",2009 Sep 15,"['Yang, Jin-Long', 'Cheng, An-Chun', 'Wang, Ming-Shu', 'Pan, Kang-Cheng', 'Li, Min', 'Guo, Yu-Fei', 'Li, Chuan-Feng', 'Zhu, De-Kang', 'Chen, Xiao-Yue']",Virol J,,,True
9a1ed211481f2c4e15f48ec3f712e73901eb628a,PMC,The Key Role of Genomics in Modern Vaccine and Drug Design for Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pgen.1000612,PMC2752168,19855822,CC BY,"It can be argued that the arrival of the “genomics era” has significantly shifted the paradigm of vaccine and therapeutics development from microbiological to sequence-based approaches. Genome sequences provide a previously unattainable route to investigate the mechanisms that underpin pathogenesis. Genomics, transcriptomics, metabolomics, structural genomics, proteomics, and immunomics are being exploited to perfect the identification of targets, to design new vaccines and drugs, and to predict their effects in patients. Furthermore, human genomics and related studies are providing insights into aspects of host biology that are important in infectious disease. This ever-growing body of genomic data and new genome-based approaches will play a critical role in the future to enable timely development of vaccines and therapeutics to control emerging infectious diseases.",2009 Oct 26,"['Seib, Kate L.', 'Dougan, Gordon', 'Rappuoli, Rino']",PLoS Genet,,,True
0d12fa6f695fdb75443b00c49514e7850ef461e5,PMC,Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1,http://dx.doi.org/10.1371/journal.pone.0007211,PMC2752805,19809496,CC BY,"BACKGROUND: Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Given that the C-type lectin receptor, dendritic cell-specific ICAM-grabbing non-integrin-related (DC-SIGNR, also known as CD209L or liver/lymph node–specific ICAM-grabbing non-integrin (L-SIGN)), can interact with pathogens including HIV-1 and is expressed at the maternal-fetal interface, we hypothesized that it could influence MTCT of HIV-1. METHODS AND FINDINGS: To investigate the potential role of DC-SIGNR in MTCT of HIV-1, we carried out a genetic association study of DC-SIGNR in a well-characterized cohort of 197 HIV-infected mothers and their infants recruited in Harare, Zimbabwe. Infants harbouring two copies of DC-SIGNR H1 and/or H3 haplotypes (H1-H1, H1-H3, H3-H3) had a 3.6-fold increased risk of in utero (IU) (P = 0.013) HIV-1 infection and a 5.7-fold increased risk of intrapartum (IP) (P = 0.025) HIV-1 infection after adjusting for a number of maternal factors. The implicated H1 and H3 haplotypes share two single nucleotide polymorphisms (SNPs) in promoter region (p-198A) and intron 2 (int2-180A) that were associated with increased risk of both IU (P = 0.045 and P = 0.003, respectively) and IP (P = 0.025, for int2-180A) HIV-1 infection. The promoter variant reduced transcriptional activity in vitro. In homozygous H1 infants bearing both the p-198A and int2-180A mutations, we observed a 4-fold decrease in the level of placental DC-SIGNR transcripts, disproportionately affecting the expression of membrane-bound isoforms compared to infant noncarriers (P = 0.011). CONCLUSION: These results suggest that DC-SIGNR plays a crucial role in MTCT of HIV-1 and that impaired placental DC-SIGNR expression increases risk of transmission.",2009 Oct 7,"['Boily-Larouche, Geneviève', 'Iscache, Anne-Laure', 'Zijenah, Lynn S.', 'Humphrey, Jean H.', 'Mouland, Andrew J.', 'Ward, Brian J.', 'Roger, Michel']",PLoS One,,,True
0f157fb0a719dd0d52fb921fb1369ccb6477636e,PMC,Proteomics computational analyses suggest that the bornavirus glycoprotein is a class III viral fusion protein (γ penetrene),http://dx.doi.org/10.1186/1743-422X-6-145,PMC2753318,19765297,CC BY,"BACKGROUND: Borna disease virus (BDV) is the type member of the Bornaviridae, a family of viruses that induce often fatal neurological diseases in horses, sheep and other animals, and have been proposed to have roles in certain psychiatric diseases of humans. The BDV glycoprotein (G) is an extensively glycosylated protein that migrates with an apparent molecular mass of 84,000 to 94,000 kilodaltons (kDa). BDV G is post-translationally cleaved by the cellular subtilisin-like protease furin into two subunits, a 41 kDa amino terminal protein GP1 and a 43 kDa carboxyl terminal protein GP2. RESULTS: Class III viral fusion proteins (VFP) encoded by members of the Rhabdoviridae, Herpesviridae and Baculoviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Proteomics computational analyses suggest that the structural/functional motifs that characterize class III VFP are located collinearly in BDV G. Structural models were established for BDV G based on the post-fusion structure of a prototypic class III VFP, vesicular stomatitis virus glycoprotein (VSV G). CONCLUSION: These results suggest that G encoded by members of the Bornavirdae are class III VFPs (gamma-penetrenes).",2009 Sep 18,"['Garry, Courtney E', 'Garry, Robert F']",Virol J,,,True
8c78151fa23bf78cc20b2e2c5c0b47d79d12a1a6,PMC,An effective docking strategy for virtual screening based on multi-objective optimization algorithm,http://dx.doi.org/10.1186/1471-2105-10-58,PMC2753843,19210777,CC BY,"BACKGROUND: Development of a fast and accurate scoring function in virtual screening remains a hot issue in current computer-aided drug research. Different scoring functions focus on diverse aspects of ligand binding, and no single scoring can satisfy the peculiarities of each target system. Therefore, the idea of a consensus score strategy was put forward. Integrating several scoring functions, consensus score re-assesses the docked conformations using a primary scoring function. However, it is not really robust and efficient from the perspective of optimization. Furthermore, to date, the majority of available methods are still based on single objective optimization design. RESULTS: In this paper, two multi-objective optimization methods, called MOSFOM, were developed for virtual screening, which simultaneously consider both the energy score and the contact score. Results suggest that MOSFOM can effectively enhance enrichment and performance compared with a single score. For three different kinds of binding sites, MOSFOM displays an excellent ability to differentiate active compounds through energy and shape complementarity. EFMOGA performed particularly well in the top 2% of database for all three cases, whereas MOEA_Nrg and MOEA_Cnt performed better than the corresponding individual scoring functions if the appropriate type of binding site was selected. CONCLUSION: The multi-objective optimization method was successfully applied in virtual screening with two different scoring functions that can yield reasonable binding poses and can furthermore, be ranked with the potentially compromised conformations of each compound, abandoning those conformations that can not satisfy overall objective functions.",2009 Feb 11,"['Li, Honglin', 'Zhang, Hailei', 'Zheng, Mingyue', 'Luo, Jie', 'Kang, Ling', 'Liu, Xiaofeng', 'Wang, Xicheng', 'Jiang, Hualiang']",BMC Bioinformatics,,,True
73687cb6e2232dce920704c44684080babf9cbfa,PMC,An effective docking strategy for virtual screening based on multi-objective optimization algorithm,http://dx.doi.org/10.1186/1471-2105-10-58,PMC2753843,19210777,CC BY,"BACKGROUND: Development of a fast and accurate scoring function in virtual screening remains a hot issue in current computer-aided drug research. Different scoring functions focus on diverse aspects of ligand binding, and no single scoring can satisfy the peculiarities of each target system. Therefore, the idea of a consensus score strategy was put forward. Integrating several scoring functions, consensus score re-assesses the docked conformations using a primary scoring function. However, it is not really robust and efficient from the perspective of optimization. Furthermore, to date, the majority of available methods are still based on single objective optimization design. RESULTS: In this paper, two multi-objective optimization methods, called MOSFOM, were developed for virtual screening, which simultaneously consider both the energy score and the contact score. Results suggest that MOSFOM can effectively enhance enrichment and performance compared with a single score. For three different kinds of binding sites, MOSFOM displays an excellent ability to differentiate active compounds through energy and shape complementarity. EFMOGA performed particularly well in the top 2% of database for all three cases, whereas MOEA_Nrg and MOEA_Cnt performed better than the corresponding individual scoring functions if the appropriate type of binding site was selected. CONCLUSION: The multi-objective optimization method was successfully applied in virtual screening with two different scoring functions that can yield reasonable binding poses and can furthermore, be ranked with the potentially compromised conformations of each compound, abandoning those conformations that can not satisfy overall objective functions.",2009 Feb 11,"['Li, Honglin', 'Zhang, Hailei', 'Zheng, Mingyue', 'Luo, Jie', 'Kang, Ling', 'Liu, Xiaofeng', 'Wang, Xicheng', 'Jiang, Hualiang']",BMC Bioinformatics,,,False
670ade9d86b2fb507104d011a048323450e21b59,PMC,Efficient oligonucleotide probe selection for pan-genomic tiling arrays,http://dx.doi.org/10.1186/1471-2105-10-293,PMC2753849,19758451,CC BY,"BACKGROUND: Array comparative genomic hybridization is a fast and cost-effective method for detecting, genotyping, and comparing the genomic sequence of unknown bacterial isolates. This method, as with all microarray applications, requires adequate coverage of probes targeting the regions of interest. An unbiased tiling of probes across the entire length of the genome is the most flexible design approach. However, such a whole-genome tiling requires that the genome sequence is known in advance. For the accurate analysis of uncharacterized bacteria, an array must query a fully representative set of sequences from the species' pan-genome. Prior microarrays have included only a single strain per array or the conserved sequences of gene families. These arrays omit potentially important genes and sequence variants from the pan-genome. RESULTS: This paper presents a new probe selection algorithm (PanArray) that can tile multiple whole genomes using a minimal number of probes. Unlike arrays built on clustered gene families, PanArray uses an unbiased, probe-centric approach that does not rely on annotations, gene clustering, or multi-alignments. Instead, probes are evenly tiled across all sequences of the pan-genome at a consistent level of coverage. To minimize the required number of probes, probes conserved across multiple strains in the pan-genome are selected first, and additional probes are used only where necessary to span polymorphic regions of the genome. The viability of the algorithm is demonstrated by array designs for seven different bacterial pan-genomes and, in particular, the design of a 385,000 probe array that fully tiles the genomes of 20 different Listeria monocytogenes strains with overlapping probes at greater than twofold coverage. CONCLUSION: PanArray is an oligonucleotide probe selection algorithm for tiling multiple genome sequences using a minimal number of probes. It is capable of fully tiling all genomes of a species on a single microarray chip. These unique pan-genome tiling arrays provide maximum flexibility for the analysis of both known and uncharacterized strains.",2009 Sep 16,"['Phillippy, Adam M', 'Deng, Xiangyu', 'Zhang, Wei', 'Salzberg, Steven L']",BMC Bioinformatics,,,True
265121b026dccf527cd9cc00dbd28a425ba5510f,PMC,"Nutritional Status, Breastfeeding, and Evolution of Infants with Acute Viral Bronchiolitis",,PMC2754025,18330067,CC BY,"Acute viral bronchiolitis is a common respiratory infectious disease of infancy. A prospective study was carried out with 175 infants aged up to six months to evaluate their nutritional and breastfeeding status as possible risk factors for unfavourable evolution of previously-healthy infants from a care hospital. Immunofluorescence test for virus and anthropometric assessment were performed. Outcomes were length of oxygen-use, length of hospital stay, and type of hospital unit needed. Seventy-three percent of the infants were well-nourished, 6% undernourished, 8.6% at a nutritional risk, 10.9% overweight, and 1.7% obese. Eighty-one percent of the undernourished and nutritionally at-risk infants and 72% of the well-nourished, overweight, and obese infants did not receive exclusive breastfeeding. The median length of hospital stay was four days and of oxygen-use was 60 hours. The nutritional status did not affect the clinical course of previously-healthy infants with acute viral brochiolitis. The duration of exclusive breastfeeding, but not type of breastfeeding, was inversely related to the length of oxygen-use and the length of hospital stay. Shorter exclusive breastfeeding was observed in infants who were assigned to a paediatric ward or to an intensive care unit. In conclusion, longer duration of breastfeeding was associated with better clinical outcomes.",2007 Sep,"['Dornelles, Cristina T.L.', 'Piva, Jefferson P.', 'Marostica, Paulo J.C.']",J Health Popul Nutr,,,True
fe83b78b82d15a20c4c1b07f472785d851b5f982,PMC,Procalcitonin levels and bacterial aetiology among COPD patients admitted to the ICU with severe pneumonia: a prospective cohort study,http://dx.doi.org/10.1186/1471-2334-9-157,PMC2754485,19772586,CC BY,"BACKGROUND: Serum procalcitonin (PCT) is considered useful in predicting the likeliness of developing bacterial infections in emergency setting. In this study, we describe PCT levels overtime and their relationship with bacterial infection in chronic obstructive pulmonary disease (COPD) critically ill patients with pneumonia. METHODS: We conducted a prospective cohort study in an ICU of a University Hospital. All consecutive COPD patients admitted for pneumonia between September 2005 and September 2006 were included. Respiratory samples were tested for the presence of bacteria and viruses. Procalcitonin was sequentially assessed and patients classified according to the probability of the presence of a bacterial infection. RESULTS: Thirty four patients were included. The PCT levels were assessed in 32/34 patients, median values were: 0.493 μg/L [IQR, 0.131 to 1.471] at the time of admission, 0.724 μg/L [IQR, 0.167 to 2.646] at six hours, and 0.557 μg/L [IQR, 0.123 to 3.4] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 μg/L in 3/32 (9%) patients and greater than 0.25 μg/L in 22/32 (69%) patients, suggesting low and high probability of bacterial infection, respectively. Fifteen bacteria and five viruses were detected in 15/34 (44%) patients. Bacteria were not detected in patients with PCTmax levels < 0.1 μg/L. In contrast, bacteria were detected in 4/7 (57%) patients estimated unlikely to have a bacterial infection by PCT levels (PCTmax > 0.1 and < 0.25 μg/L). CONCLUSION: Based on these results we suggest that a PCT level cut off > 0.1 μg/L may be more appropriate than 0.25 μg/L (previously proposed for non severe lower respiratory tract infection) to predict the probability of a bacterial infection in severe COPD patients with pneumonia. Further studies testing procalcitonin-based antibiotic strategies are needed in COPD patients with severe pneumonia.",2009 Sep 21,"['Daubin, Cédric', 'Parienti, Jean-Jacques', 'Fradin, Sabine', 'Vabret, Astrid', 'Ramakers, Michel', 'Terzi, Nicolas', 'Freymuth, François', 'Charbonneau, Pierre', 'du Cheyron, Damien']",BMC Infect Dis,,,True
3041d890310a050dfc5725636a7b26a23b9d40aa,PMC,The Replicase Gene of Avian Coronavirus Infectious Bronchitis Virus Is a Determinant of Pathogenicity,http://dx.doi.org/10.1371/journal.pone.0007384,PMC2754531,19816578,CC BY,"We have previously demonstrated that the replacement of the S gene from an avirulent strain (Beaudette) of infectious bronchitis virus (IBV) with an S gene from a virulent strain (M41) resulted in a recombinant virus (BeauR-M41(S)) with the in vitro cell tropism of the virulent virus but that was still avirulent. In order to investigate whether any of the other structural or accessory genes played a role in pathogenicity we have now replaced these from the Beaudette strain with those from M41. The recombinant IBV was in effect a chimaeric virus with the replicase gene derived from Beaudette and the rest of the genome from M41. This demonstrated that it is possible to exchange a large region of the IBV genome, approximately 8.4 kb, using our transient dominant selection method. Recovery of a viable recombinant IBV also demonstrated that it is possible to interchange a complete replicase gene as we had in effect replaced the M41 replicase gene with the Beaudette derived gene. Analysis of the chimaeric virus showed that it was avirulent indicating that none of the structural or accessory genes derived from a virulent isolate of IBV were able to restore virulence and that therefore, the loss of virulence associated with the Beaudette strain resides in the replicase gene.",2009 Oct 9,"['Armesto, Maria', 'Cavanagh, Dave', 'Britton, Paul']",PLoS One,,,True
85581e91ad30b4385cbd57496aaaf5f19ff33080,PMC,Computational Resources in Infectious Disease: Limitations and Challenges,http://dx.doi.org/10.1371/journal.pcbi.1000481,PMC2756590,19855825,CC BY,,2009 Oct 26,"['Berglund, Eva C.', 'Nystedt, Björn', 'Andersson, Siv G. E.']",PLoS Comput Biol,,,True
45f1fd0f1962aa8162216270b1a97e57e0708b18,PMC,"The Role of Genomics in the Identification, Prediction, and Prevention of Biological Threats",http://dx.doi.org/10.1371/journal.pbio.1000217,PMC2757898,19855827,CC BY,"In all likelihood, it is only a matter of time before our public health system will face a major biological threat, whether intentionally dispersed or originating from a known or newly emerging infectious disease. It is necessary not only to increase our reactive “biodefense,” but also to be proactive and increase our preparedness. To achieve this goal, it is essential that the scientific and public health communities fully embrace the genomic revolution, and that novel bioinformatic and computing tools necessary to make great strides in our understanding of these novel and emerging threats be developed. Genomics has graduated from a specialized field of science to a research tool that soon will be routine in research laboratories and clinical settings. Because the technology is becoming more affordable, genomics can and should be used proactively to build our preparedness and responsiveness to biological threats. All pieces, including major continued funding, advances in next-generation sequencing technologies, bioinformatics infrastructures, and open access to data and metadata, are being set in place for genomics to play a central role in our public health system.",2009 Oct 26,"['Fricke, W. Florian', 'Rasko, David A.', 'Ravel, Jacques']",PLoS Biol,,,True
02974b9466bf593193d05ada669d7ff0567bb657,PMC,Can an Infectious Disease Genomics Project Predict and Prevent the Next Pandemic?,http://dx.doi.org/10.1371/journal.pbio.1000219,PMC2757903,19855828,CC BY,Infectious diseases need a globally coordinated genomic-based movement linking sequencing efforts to development of response tools to mitigate the impact of existing and emerging threats.,2009 Oct 26,"['Gupta, Rajesh', 'Michalski, Mark H.', 'Rijsberman, Frank R.']",PLoS Biol,,,True
f8bd14ffe1272be4d4c25d0d6f23f2479c0d1475,PMC,Inhibition of RNA Recruitment and Replication of an RNA Virus by Acridine Derivatives with Known Anti-Prion Activities,http://dx.doi.org/10.1371/journal.pone.0007376,PMC2757906,19823675,CC BY,"BACKGROUND: Small molecule inhibitors of RNA virus replication are potent antiviral drugs and useful to dissect selected steps in the replication process. To identify antiviral compounds against Tomato bushy stunt virus (TBSV), a model positive stranded RNA virus, we tested acridine derivatives, such as chlorpromazine (CPZ) and quinacrine (QC), which are active against prion-based diseases. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that CPZ and QC compounds inhibited TBSV RNA accumulation in plants and in protoplasts. In vitro assays revealed that the inhibitory effects of these compounds were manifested at different steps of TBSV replication. QC was shown to have an effect on multiple steps, including: (i) inhibition of the selective binding of the p33 replication protein to the viral RNA template, which is required for recruitment of viral RNA for replication; (ii) reduction of minus-strand synthesis by the tombusvirus replicase; and (iii) inhibition of translation of the uncapped TBSV genomic RNA. In contrast, CPZ was shown to inhibit the in vitro assembly of the TBSV replicase, likely due to binding of CPZ to intracellular membranes, which are important for RNA virus replication. CONCLUSION/SIGNIFICANCE: Since we found that CPZ was also an effective inhibitor of other plant viruses, including Tobacco mosaic virus and Turnip crinkle virus, it seems likely that CPZ has a broad range of antiviral activity. Thus, these inhibitors constitute effective tools to study similarities in replication strategies of various RNA viruses.",2009 Oct 13,"['Sasvari, Zsuzsanna', 'Bach, Stéphane', 'Blondel, Marc', 'Nagy, Peter D.']",PLoS One,,,True
341032e0d9e1730bdf19b1742d4f9e32c544d083,PMC,Genomics of Emerging Infectious Disease: A PLoS Collection,http://dx.doi.org/10.1371/journal.pbio.1000224,PMC2757914,19855830,CC BY,,2009 Oct 26,"['Eisen, Jonathan A.', 'MacCallum, Catriona J.']",PLoS Biol,,,True
82ec1cd41017fab2d523840ae9fb3f30dbeeab55,PMC,Up-Regulation of Hepatitis C Virus Replication and Production by Inhibition of MEK/ERK Signaling,http://dx.doi.org/10.1371/journal.pone.0007498,PMC2759292,19834602,CC BY,"BACKGROUND: Viruses interact with and exploit the host cellular machinery for their multiplication and propagation. The MEK/ERK signaling pathway positively regulates replication of many RNA viruses. However, whether and how this signaling pathway affects hepatitis C virus (HCV) replication and production is not well understood. METHODS AND RESULTS: In this study, we took advantage of two well-characterized MEK/ERK inhibitors and MEK/ERK dominant negative mutants and investigated the roles of the MEK/ERK signaling pathway in HCV gene expression and replication. We showed that inhibition of MEK/ERK signaling enhanced HCV gene expression, plus- and minus-strand RNA synthesis, and virus production. In addition, we showed that this enhancement was independent of interferon-α (IFN-α) antiviral activity and did not require prior activation of the MEK/ERK signaling pathway. Furthermore, we showed that only MEK and ERK-2 but not ERK-1 was involved in HCV replication, likely through regulation of HCV RNA translation. CONCLUSIONS: Taken together, these results demonstrate a negative regulatory role of the MEK/ERK signaling pathway in HCV replication and suggest a potential risk in targeting this signaling pathway to treat and prevent neoplastic transformation of HCV-infected liver cells.",2009 Oct 16,"['Ndjomou, Jean', 'Park, In-woo', 'Liu, Ying', 'Mayo, Lindsey D.', 'He, Johnny J.']",PLoS One,,,True
4ea207323d2fedf5b4f5a4cbb8fd1acd100df8a8,PMC,Mutagenesis of the fusion peptide-like domain of hepatitis C virus E1 glycoprotein: involvement in cell fusion and virus entry,http://dx.doi.org/10.1186/1423-0127-16-89,PMC2759930,19778418,CC BY,"BACKGROUND: Envelope (E) glycoprotein E2 of the hepatitis C virus (HCV) mediates binding of the virus to target cell receptors. Nevertheless, the precise role of E1 in viral entry remains elusive. METHODS: To understand the involvement of the fusion peptide-like domain positioned at residues 264 to 290 within envelope glycoprotein E1 in HCV infection, mutants with Ala and Asn substitutions for residues conserved between HCV and E proteins of flaviviruses or the fusion proteins of paramyxoviruses were constructed by site-directed mutagenesis and their effects on membrane fusion and viral infectivity were examined. RESULTS: None of these mutations affected the synthesis or cell surface expression of envelope proteins, nor did they alter the formation of a non-covalent E1-E2 heterodimer or E2 binding to the large extracellular loop of CD81. The Cys residues located at positions 272 and 281 were unlikely involved in intra- or intermolecular disulfide bond formation. With the exception of the G267A mutant, which showed increased cell fusion, other mutants displayed reduced or marginally inhibited cell fusion capacities compared to the wild-type (WT) E1E2. The G267A mutant was also an exception in human immunodeficiency virus type 1 (HIV-1)/HCV E1E2 pseudotyping analyses, in that it showed higher one-cycle infectivity; all other mutants exhibited greatly or partially reduced viral entry versus the WT pseudotype. All but the G278A and D279N mutants showed a WT-like profile of E1E2 incorporation into HIV-1 particles. Since C272A, C281A, G282A, and G288A pseudotypes bound to Huh7 cells as effectively as did the WT pseudotype, the reduced infectivity of these pseudotypes was due to their ability to inhibit cell fusion. CONCLUSION: Our results indicate that specific residues, but not the structure, of this fusion peptide-like domain are required for mediating cell fusion and viral entry.",2009 Sep 24,"['Li, Hsiao-Fen', 'Huang, Chia-Hsuan', 'Ai, Li-Shuang', 'Chuang, Chin-Kai', 'Chen, Steve SL']",J Biomed Sci,,,True
80a735987ea3897dc5e33a859e1a80310babb2da,PMC,Detection of HIV-1 RNA/DNA and CD4 mRNA in feces and urine from chronic HIV-1 infected subjects with and without anti-retroviral therapy,http://dx.doi.org/10.1186/1742-6405-6-20,PMC2761414,19799780,CC BY,"HIV-1 infects gut associated lymphoid tissues (GALT) very early after transmission by multiple routes. The infected GALT consequently serves as the major reservoir for HIV-1 infection and could constantly shed HIV-1 and CD4(+ )T cells into the intestinal lumen. To examine this hypothesis, we monitored HIV-1 RNA/DNA and CD4 mRNA in fecal samples of chronically infected subjects with and without antiretroviral therapy (ART). We compared this to levels of HIV-1 RNA/DNA in urine and blood from the same subjects. Our results show that HIV-1 DNA, RNA and CD4 mRNA were detected in 8%, 19% and 31% respectively, of feces samples from infected subjects with detectable plasma viral load, and were not detected in any of subjects on ART with undetectable plasma viral load. In urine samples, HIV-1 DNA was detected in 24% of infected subjects with detectable plasma viral load and 23% of subjects on ART with undetectable plasma viral load. Phylogenetic analysis of the envelope sequences of HIV-1 revealed distinct virus populations in concurrently collected serum, feces and urine samples from one subject. In addition, our study demonstrated for the first time the presence of CD4 mRNA in fecal specimens of HIV-1 infected subjects, which could be used to assess GALT pathogenesis in HIV-1 infection.",2009 Oct 2,"['Chakrabarti, Ayan K', 'Caruso, Lori', 'Ding, Ming', 'Shen, Chengli', 'Buchanan, William', 'Gupta, Phalguni', 'Rinaldo, Charles R', 'Chen, Yue']",AIDS Res Ther,,,True
69422fc5757c3c88a574d830594a4dc1a06337b9,PMC,Small islands and pandemic influenza: Potential benefits and limitations of travel volume reduction as a border control measure,http://dx.doi.org/10.1186/1471-2334-9-160,PMC2761921,19788751,CC BY,"BACKGROUND: Some island nations have explicit components of their influenza pandemic plans for providing travel warnings and restricting incoming travellers. But the potential value of such restrictions has not been quantified. METHODS: We developed a probabilistic model and used parameters from a published model (i.e., InfluSim) and travel data from Pacific Island Countries and Territories (PICTs). RESULTS: The results indicate that of the 17 PICTs with travel data, only six would be likely to escape a major pandemic with a viral strain of relatively low contagiousness (i.e., for R(0 )= 1.5) even when imposing very tight travel volume reductions of 99% throughout the course of the pandemic. For a more contagious viral strain (R(0 )= 2.25) only five PICTs would have a probability of over 50% to escape. The total number of travellers during the pandemic must not exceed 115 (for R(0 )= 3.0) or 380 (for R(0 )= 1.5) if a PICT aims to keep the probability of pandemic arrival below 50%. CONCLUSION: These results suggest that relatively few island nations could successfully rely on intensive travel volume restrictions alone to avoid the arrival of pandemic influenza (or subsequent waves). Therefore most island nations may need to plan for multiple additional interventions (e.g., screening and quarantine) to raise the probability of remaining pandemic free or achieving substantial delay in pandemic arrival.",2009 Sep 29,"['Eichner, Martin', 'Schwehm, Markus', 'Wilson, Nick', 'Baker, Michael G']",BMC Infect Dis,,,True
ab23c1ed37392d4e2dbbd809e62171775e75369b,PMC,Evasion by Stealth: Inefficient Immune Activation Underlies Poor T Cell Response and Severe Disease in SARS-CoV-Infected Mice,http://dx.doi.org/10.1371/journal.ppat.1000636,PMC2762542,19851468,CC BY,"Severe Acute Respiratory Syndrome caused substantial morbidity and mortality during the 2002–2003 epidemic. Many of the features of the human disease are duplicated in BALB/c mice infected with a mouse-adapted version of the virus (MA15), which develop respiratory disease with high morbidity and mortality. Here, we show that severe disease is correlated with slow kinetics of virus clearance and delayed activation and transit of respiratory dendritic cells (rDC) to the draining lymph nodes (DLN) with a consequent deficient virus-specific T cell response. All of these defects are corrected when mice are treated with liposomes containing clodronate, which deplete alveolar macrophages (AM). Inhibitory AMs are believed to prevent the development of immune responses to environmental antigens and allergic responses by interacting with lung dendritic cells and T cells. The inhibitory effects of AM can also be nullified if mice or AMs are pretreated with poly I:C, which directly activate AMs and rDCs through toll-like receptors 3 (TLR3). Further, adoptive transfer of activated but not resting bone marrow–derived dendritic cells (BMDC) protect mice from lethal MA15 infection. These results may be relevant for SARS in humans, which is also characterized by prolonged virus persistence and delayed development of a SARS-CoV-specific immune response in individuals with severe disease.",2009 Oct 23,"['Zhao, Jincun', 'Zhao, Jingxian', 'Van Rooijen, Nico', 'Perlman, Stanley']",PLoS Pathog,,,True
9721af1b88d60abbff468d841941f85a13731861,PMC,Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis,http://dx.doi.org/10.1136/thx.2008.112466,PMC2764123,19574243,CC BY,"BACKGROUND: Pseudomonas aeruginosa is the most common bacterial pathogen in patients with cystic fibrosis (CF). Current infection control guidelines aim to prevent transmission via contact and respiratory droplet routes and do not consider the possibility of airborne transmission. It was hypothesised that subjects with CF produce viable respirable bacterial aerosols with coughing. METHODS: A cross-sectional study was undertaken of 15 children and 13 adults with CF, 26 chronically infected with P aeruginosa. A cough aerosol sampling system enabled fractioning of respiratory particles of different sizes and culture of viable Gram-negative non-fermentative bacteria. Cough aerosols were collected during 5 min of voluntary coughing and during a sputum induction procedure when tolerated. Standardised quantitative culture and genotyping techniques were used. RESULTS: P aeruginosa was isolated in cough aerosols of 25 subjects (89%), 22 of whom produced sputum samples. P aeruginosa from sputum and paired cough aerosols were indistinguishable by molecular typing. In four cases the same genotype was isolated from ambient room air. Approximately 70% of viable aerosols collected during voluntary coughing were of particles ⩽3.3 μm aerodynamic diameter. P aeruginosa, Burkholderia cenocepacia, Stenotrophomonas maltophilia and Achromobacter xylosoxidans were cultivated from respiratory particles in this size range. Positive room air samples were associated with high total counts in cough aerosols (p = 0.003). The magnitude of cough aerosols was associated with higher forced expiratory volume in 1 s (r = 0.45, p = 0.02) and higher quantitative sputum culture results (r = 0.58, p = 0.008). CONCLUSION: During coughing, patients with CF produce viable aerosols of P aeruginosa and other Gram-negative bacteria of respirable size range, suggesting the potential for airborne transmission.",2009 Nov 1,"['Wainwright, C E', 'France, M W', 'O’Rourke, P', 'Anuj, S', 'Kidd, T J', 'Nissen, M D', 'Sloots, T P', 'Coulter, C', 'Ristovski, Z', 'Hargreaves, M', 'Rose, B R', 'Harbour, C', 'Bell, S C', 'Fennelly, K P']",Thorax,,,True
ffef8194e52de95fe345db7dd12fe3185d786978,PMC,Evidence of HIV-1 adaptation to host HLA alleles following chimp-to-human transmission,http://dx.doi.org/10.1186/1743-422X-6-164,PMC2765438,19818146,CC BY,"BACKGROUND: The cytotoxic T-lymphocyte immune response is important in controlling HIV-1 replication in infected humans. In this immune pathway, viral peptides within infected cells are presented to T-lymphocytes by the polymorphic human leukocyte antigens (HLA). HLA alleles exert selective pressure on the peptide regions and immune escape mutations that occur at some of the targeted sites can enable the virus to adapt to the infected host. The pattern of ongoing immune escape and reversion associated with several human HLA alleles has been studied extensively. Such mutations revert upon transmission to a host without the HLA allele because the escape mutation incurs a fitness cost. However, to-date there has been little attempt to study permanent loss of CTL epitopes due to escape mutations without an effect on fitness. RESULTS: Here, we set out to determine the extent of adaptation of HIV-1 to three well-characterized HLA alleles during the initial exposure of the virus to the human cytotoxic immune responses following transmission from chimpanzee. We generated a chimpanzee consensus sequence to approximate the virus sequence that was initially transmitted to the human host and used a method based on peptide binding affinity to HLA crystal structures to predict peptides that were potentially targeted by the HLA alleles on this sequence. Next, we used codon-based phylogenetic models to quantify the average selective pressure that acted on these regions during the period immediately following the zoonosis event, corresponding to the branch of the phylogenetic tree leading to the common ancestor of all of the HIV-1 sequences. Evidence for adaptive evolution during this period was observed at regions recognised by HLA A*6801 and A*0201, both of which are common in African populations. No evidence of adaptive evolution was observed at sites targeted by HLA-B*2705, which is a rare allele in African populations. CONCLUSION: Our results suggest that the ancestral HIV-1 virus experienced a period of positive selective pressure due to immune responses associated with HLA alleles that were common in the infected human population. We propose that this resulted in permanent escape from immune responses targeting unconstrained regions of the virus.",2009 Oct 10,"['Ngandu, Nobubelo K', 'Seoighe, Cathal', 'Scheffler, Konrad']",Virol J,,,True
9ffa106061fd815e4bb93389274819e640dfb840,PMC,"Initial psychological responses to Influenza A, H1N1 (""Swine flu"")",http://dx.doi.org/10.1186/1471-2334-9-166,PMC2765446,19807908,CC BY,"BACKGROUND: The outbreak of the pandemic flu, Influenza A H1N1 (Swine Flu) in early 2009, provided a major challenge to health services around the world. Previous pandemics have led to stockpiling of goods, the victimisation of particular population groups, and the cancellation of travel and the boycotting of particular foods (e.g. pork). We examined initial behavioural and attitudinal responses towards Influenza A, H1N1 (""Swine flu"") in the six days following the WHO pandemic alert level 5, and regional differences in these responses. METHODS: 328 respondents completed a cross-sectional Internet or paper-based questionnaire study in Malaysia (N = 180) or Europe (N = 148). Measures assessed changes in transport usage, purchase of preparatory goods for a pandemic, perceived risk groups, indicators of anxiety, assessed estimated mortality rates for seasonal flu, effectiveness of seasonal flu vaccination, and changes in pork consumption RESULTS: 26% of the respondents were 'very concerned' about being a flu victim (42% Malaysians, 5% Europeans, p < .001). 36% reported reduced public transport use (48% Malaysia, 22% Europe, p < .001), 39% flight cancellations (56% Malaysia, 17% Europe, p < .001). 8% had purchased preparatory materials (e.g. face masks: 8% Malaysia, 7% Europe), 41% Malaysia (15% Europe) intended to do so (p < .001). 63% of Europeans, 19% of Malaysians had discussed the pandemic with friends (p < .001). Groups seen as at 'high risk' of infection included the immune compromised (mentioned by 87% respondents), pig farmers (70%), elderly (57%), prostitutes/highly sexually active (53%), and the homeless (53%). In data collected only in Europe, 64% greatly underestimated the mortality rates of seasonal flu, 26% believed seasonal flu vaccination gave protection against swine flu. 7% had reduced/stopped eating pork. 3% had purchased anti-viral drugs for use at home, while 32% intended to do so if the pandemic worsened. CONCLUSION: Initial responses to Influenza A show large regional differences in anxiety, with Malaysians more anxious and more likely to reduce travel and to buy masks and food. Discussions with family and friends may reinforce existing anxiety levels. Particular groups (homosexuals, prostitutes, the homeless) are perceived as at greater risk, potentially leading to increased prejudice during a pandemic. Europeans underestimated mortality of seasonal flu, and require more information about the protection given by seasonal flu inoculation.",2009 Oct 6,"['Goodwin, Robin', 'Haque, Shamsul', 'Neto, Felix', 'Myers, Lynn B']",BMC Infect Dis,,,True
74813899dfd7ad7de15228fd014c735c3410d9d9,PMC,A Neutralizing Human Monoclonal Antibody Protects against Lethal Disease in a New Ferret Model of Acute Nipah Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1000642,PMC2765826,19888339,CC0,"Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats. Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. Here, a new ferret model of Nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. Severe disease occurs with viral doses as low as 500 TCID(50) within 6 to 10 days following infection. The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues. Using this ferret model a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent. All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died. This study is the first successful post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody.",2009 Oct 30,"['Bossart, Katharine N.', 'Zhu, Zhongyu', 'Middleton, Deborah', 'Klippel, Jessica', 'Crameri, Gary', 'Bingham, John', 'McEachern, Jennifer A.', 'Green, Diane', 'Hancock, Timothy J.', 'Chan, Yee-Peng', 'Hickey, Andrew C.', 'Dimitrov, Dimiter S.', 'Wang, Lin-Fa', 'Broder, Christopher C.']",PLoS Pathog,,,True
a6d3a67189b0d60da49032d2192a681dc06f5459,PMC,The influenza A(H1N1) epidemic in Mexico. Lessons learned,http://dx.doi.org/10.1186/1478-4505-7-21,PMC2765941,19785747,CC BY,"Several influenza pandemics have taken place throughout history and it was assumed that the pandemic would emerge from a new human virus resulting from the adaptation of an avian virus strain. Mexico, since 2003 had developed a National Preparedness and Response Plan for an Influenza Pandemic focused in risk communication, health promotion, healthcare, epidemiological surveillance, strategic stockpile, research and development. This plan was challenged on April 2009, when a new influenza A(H1N1) strain of swine origen was detected in Mexico. The situation faced, the decisions and actions taken, allowed to control the first epidemic wave in the country. This document describes the critical moments faced and explicitly point out the lessons learned focused on the decided support by the government, the National Pandemic Influenza Plan, the coordination among all the government levels, the presence and solidarity of international organizations with timely and daily information, diagnosis and the positive effect on the population following the preventive hygienic measures recommended by the health authorities. The international community will be able to use the Mexican experience in the interest of global health.",2009 Sep 28,"['Córdova-Villalobos, José A', 'Sarti, Elsa', 'Arzoz-Padrés, Jacqueline', 'Manuell-Lee, Gabriel', 'Méndez, Josefina Romero', 'Kuri-Morales, Pablo']",Health Res Policy Syst,,,True
c851e8a17951dc6f713c2a832e6a516f72154a79,PMC,A Protective Role for ELR+ Chemokines during Acute Viral Encephalomyelitis,http://dx.doi.org/10.1371/journal.ppat.1000648,PMC2766051,19893623,CC BY,"The functional role of ELR-positive CXC chemokines in host defense during acute viral-induced encephalomyelitis was determined. Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of mice resulted in the rapid mobilization of PMNs expressing the chemokine receptor CXCR2 into the blood. Migration of PMNs to the CNS coincided with increased expression of transcripts specific for the CXCR2 ELR-positive chemokine ligands CXCL1, CXCL2, and CXCL5 within the brain. Treatment of JHMV-infected mice with anti-CXCR2 blocking antibody reduced PMN trafficking into the CNS by >95%, dampened MMP-9 activity, and abrogated blood-brain-barrier (BBB) breakdown. Correspondingly, CXCR2 neutralization resulted in diminished infiltration of virus-specific T cells, an inability to control viral replication within the brain, and 100% mortality. Blocking CXCR2 signaling did not impair the generation of virus-specific T cells, indicating that CXCR2 is not required to tailor anti-JHMV T cell responses. Evaluation of mice in which CXCR2 is genetically silenced (CXCR2−/− mice) confirmed that PMNs neither expressed CXCR2 nor migrated in response to ligands CXCL1, CXCL2, or CXCL5 in an in vitro chemotaxis assay. Moreover, JHMV infection of CXCR2−/− mice resulted in an approximate 60% reduction of PMN migration into the CNS, yet these mice survived infection and controlled viral replication within the brain. Treatment of JHMV-infected CXCR2−/− mice with anti-CXCR2 antibody did not modulate PMN migration nor alter viral clearance or mortality, indicating the existence of compensatory mechanisms that facilitate sufficient migration of PMNs into the CNS in the absence of CXCR2. Collectively, these findings highlight a previously unappreciated role for ELR-positive chemokines in enhancing host defense during acute viral infections of the CNS.",2009 Nov 6,"['Hosking, Martin P.', 'Liu, Liping', 'Ransohoff, Richard M.', 'Lane, Thomas E.']",PLoS Pathog,,,True
e15d2db8625e8442fd8c535564897d49258d1635,PMC,A Protective Role for ELR+ Chemokines during Acute Viral Encephalomyelitis,http://dx.doi.org/10.1371/journal.ppat.1000648,PMC2766051,19893623,CC BY,"The functional role of ELR-positive CXC chemokines in host defense during acute viral-induced encephalomyelitis was determined. Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of mice resulted in the rapid mobilization of PMNs expressing the chemokine receptor CXCR2 into the blood. Migration of PMNs to the CNS coincided with increased expression of transcripts specific for the CXCR2 ELR-positive chemokine ligands CXCL1, CXCL2, and CXCL5 within the brain. Treatment of JHMV-infected mice with anti-CXCR2 blocking antibody reduced PMN trafficking into the CNS by >95%, dampened MMP-9 activity, and abrogated blood-brain-barrier (BBB) breakdown. Correspondingly, CXCR2 neutralization resulted in diminished infiltration of virus-specific T cells, an inability to control viral replication within the brain, and 100% mortality. Blocking CXCR2 signaling did not impair the generation of virus-specific T cells, indicating that CXCR2 is not required to tailor anti-JHMV T cell responses. Evaluation of mice in which CXCR2 is genetically silenced (CXCR2−/− mice) confirmed that PMNs neither expressed CXCR2 nor migrated in response to ligands CXCL1, CXCL2, or CXCL5 in an in vitro chemotaxis assay. Moreover, JHMV infection of CXCR2−/− mice resulted in an approximate 60% reduction of PMN migration into the CNS, yet these mice survived infection and controlled viral replication within the brain. Treatment of JHMV-infected CXCR2−/− mice with anti-CXCR2 antibody did not modulate PMN migration nor alter viral clearance or mortality, indicating the existence of compensatory mechanisms that facilitate sufficient migration of PMNs into the CNS in the absence of CXCR2. Collectively, these findings highlight a previously unappreciated role for ELR-positive chemokines in enhancing host defense during acute viral infections of the CNS.",2009 Nov 6,"['Hosking, Martin P.', 'Liu, Liping', 'Ransohoff, Richard M.', 'Lane, Thomas E.']",PLoS Pathog,,,False
dd6da0893e5676f45747ab0ef6a4fa98007cc113,PMC,A Protective Role for ELR+ Chemokines during Acute Viral Encephalomyelitis,http://dx.doi.org/10.1371/journal.ppat.1000648,PMC2766051,19893623,CC BY,"The functional role of ELR-positive CXC chemokines in host defense during acute viral-induced encephalomyelitis was determined. Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of mice resulted in the rapid mobilization of PMNs expressing the chemokine receptor CXCR2 into the blood. Migration of PMNs to the CNS coincided with increased expression of transcripts specific for the CXCR2 ELR-positive chemokine ligands CXCL1, CXCL2, and CXCL5 within the brain. Treatment of JHMV-infected mice with anti-CXCR2 blocking antibody reduced PMN trafficking into the CNS by >95%, dampened MMP-9 activity, and abrogated blood-brain-barrier (BBB) breakdown. Correspondingly, CXCR2 neutralization resulted in diminished infiltration of virus-specific T cells, an inability to control viral replication within the brain, and 100% mortality. Blocking CXCR2 signaling did not impair the generation of virus-specific T cells, indicating that CXCR2 is not required to tailor anti-JHMV T cell responses. Evaluation of mice in which CXCR2 is genetically silenced (CXCR2−/− mice) confirmed that PMNs neither expressed CXCR2 nor migrated in response to ligands CXCL1, CXCL2, or CXCL5 in an in vitro chemotaxis assay. Moreover, JHMV infection of CXCR2−/− mice resulted in an approximate 60% reduction of PMN migration into the CNS, yet these mice survived infection and controlled viral replication within the brain. Treatment of JHMV-infected CXCR2−/− mice with anti-CXCR2 antibody did not modulate PMN migration nor alter viral clearance or mortality, indicating the existence of compensatory mechanisms that facilitate sufficient migration of PMNs into the CNS in the absence of CXCR2. Collectively, these findings highlight a previously unappreciated role for ELR-positive chemokines in enhancing host defense during acute viral infections of the CNS.",2009 Nov 6,"['Hosking, Martin P.', 'Liu, Liping', 'Ransohoff, Richard M.', 'Lane, Thomas E.']",PLoS Pathog,,,False
2d260d046e4a6ba91ec7c811f0362340f4d4a3d4,PMC,A Protective Role for ELR+ Chemokines during Acute Viral Encephalomyelitis,http://dx.doi.org/10.1371/journal.ppat.1000648,PMC2766051,19893623,CC BY,"The functional role of ELR-positive CXC chemokines in host defense during acute viral-induced encephalomyelitis was determined. Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of mice resulted in the rapid mobilization of PMNs expressing the chemokine receptor CXCR2 into the blood. Migration of PMNs to the CNS coincided with increased expression of transcripts specific for the CXCR2 ELR-positive chemokine ligands CXCL1, CXCL2, and CXCL5 within the brain. Treatment of JHMV-infected mice with anti-CXCR2 blocking antibody reduced PMN trafficking into the CNS by >95%, dampened MMP-9 activity, and abrogated blood-brain-barrier (BBB) breakdown. Correspondingly, CXCR2 neutralization resulted in diminished infiltration of virus-specific T cells, an inability to control viral replication within the brain, and 100% mortality. Blocking CXCR2 signaling did not impair the generation of virus-specific T cells, indicating that CXCR2 is not required to tailor anti-JHMV T cell responses. Evaluation of mice in which CXCR2 is genetically silenced (CXCR2−/− mice) confirmed that PMNs neither expressed CXCR2 nor migrated in response to ligands CXCL1, CXCL2, or CXCL5 in an in vitro chemotaxis assay. Moreover, JHMV infection of CXCR2−/− mice resulted in an approximate 60% reduction of PMN migration into the CNS, yet these mice survived infection and controlled viral replication within the brain. Treatment of JHMV-infected CXCR2−/− mice with anti-CXCR2 antibody did not modulate PMN migration nor alter viral clearance or mortality, indicating the existence of compensatory mechanisms that facilitate sufficient migration of PMNs into the CNS in the absence of CXCR2. Collectively, these findings highlight a previously unappreciated role for ELR-positive chemokines in enhancing host defense during acute viral infections of the CNS.",2009 Nov 6,"['Hosking, Martin P.', 'Liu, Liping', 'Ransohoff, Richard M.', 'Lane, Thomas E.']",PLoS Pathog,,,False
a7eabb9cc3d54246f76429da3a972e819d075a1d,PMC,A Protective Role for ELR+ Chemokines during Acute Viral Encephalomyelitis,http://dx.doi.org/10.1371/journal.ppat.1000648,PMC2766051,19893623,CC BY,"The functional role of ELR-positive CXC chemokines in host defense during acute viral-induced encephalomyelitis was determined. Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of mice resulted in the rapid mobilization of PMNs expressing the chemokine receptor CXCR2 into the blood. Migration of PMNs to the CNS coincided with increased expression of transcripts specific for the CXCR2 ELR-positive chemokine ligands CXCL1, CXCL2, and CXCL5 within the brain. Treatment of JHMV-infected mice with anti-CXCR2 blocking antibody reduced PMN trafficking into the CNS by >95%, dampened MMP-9 activity, and abrogated blood-brain-barrier (BBB) breakdown. Correspondingly, CXCR2 neutralization resulted in diminished infiltration of virus-specific T cells, an inability to control viral replication within the brain, and 100% mortality. Blocking CXCR2 signaling did not impair the generation of virus-specific T cells, indicating that CXCR2 is not required to tailor anti-JHMV T cell responses. Evaluation of mice in which CXCR2 is genetically silenced (CXCR2−/− mice) confirmed that PMNs neither expressed CXCR2 nor migrated in response to ligands CXCL1, CXCL2, or CXCL5 in an in vitro chemotaxis assay. Moreover, JHMV infection of CXCR2−/− mice resulted in an approximate 60% reduction of PMN migration into the CNS, yet these mice survived infection and controlled viral replication within the brain. Treatment of JHMV-infected CXCR2−/− mice with anti-CXCR2 antibody did not modulate PMN migration nor alter viral clearance or mortality, indicating the existence of compensatory mechanisms that facilitate sufficient migration of PMNs into the CNS in the absence of CXCR2. Collectively, these findings highlight a previously unappreciated role for ELR-positive chemokines in enhancing host defense during acute viral infections of the CNS.",2009 Nov 6,"['Hosking, Martin P.', 'Liu, Liping', 'Ransohoff, Richard M.', 'Lane, Thomas E.']",PLoS Pathog,,,False
75aa45fec583443ad040672ab48b2c90825a94bb,PMC,New journal selection for quantitative survey of infectious disease research: application for Asian trend analysis,http://dx.doi.org/10.1186/1471-2288-9-67,PMC2766390,19804650,CC BY,"BACKGROUND: Quantitative survey of research articles, as an application of bibliometrics, is an effective tool for grasping overall trends in various medical research fields. This type of survey has been also applied to infectious disease research; however, previous studies were insufficient as they underestimated articles published in non-English or regional journals. METHODS: Using a combination of Scopus™ and PubMed, the databases of scientific literature, and English and non-English keywords directly linked to infectious disease control, we identified international and regional infectious disease journals. In order to ascertain whether the newly selected journals were appropriate to survey a wide range of research articles, we compared the number of original articles and reviews registered in the selected journals to those in the 'Infectious Disease Category' of the Science Citation Index Expanded™ (SCI Infectious Disease Category) during 1998-2006. Subsequently, we applied the newly selected journals to survey the number of original articles and reviews originating from 11 Asian countries during the same period. RESULTS: One hundred journals, written in English or 7 non-English languages, were newly selected as infectious disease journals. The journals published 14,156 original articles and reviews of Asian origin and 118,158 throughout the world, more than those registered in the SCI Infectious Disease Category (4,621 of Asian origin and 66,518 of the world in the category). In Asian trend analysis of the 100 journals, Japan had the highest percentage of original articles and reviews in the area, and no noticeable increase in articles was revealed during the study period. China, India and Taiwan had relatively large numbers and a high increase rate of original articles among Asian countries. When adjusting the publication of original articles according to the country population and the gross domestic product (GDP), Singapore and Taiwan were the most productive. CONCLUSION: A survey of 100 selected journals is more sensitive than the SCI Infectious Disease Category from the viewpoint of avoiding underestimating the number of infectious disease research articles of Asian origin. The survey method is applicable to grasp global trends in disease research, although the method may require further development.",2009 Oct 6,"['Takahashi-Omoe, Hiromi', 'Omoe, Katsuhiko', 'Okabe, Nobuhiko']",BMC Med Res Methodol,,,True
c248b6eb16165b2b06281401eaeb99df0ba7f211,PMC,Barriers and supports to implementation of MDI/spacer use in nine Canadian pediatric emergency departments: a qualitative study,http://dx.doi.org/10.1186/1748-5908-4-65,PMC2766417,19828086,CC BY,"BACKGROUND: Despite recent research supporting the use of metered dose inhalers with spacer devices (MDI/spacers) in pediatric emergency departments (PEDs) for acute exacerbations of asthma, uptake of this practice has been slow. The objectives of this study were to determine the barriers and supports to implementing MDI/spacer research and to identify factors associated with early and late adoption of MDI/spacers in Canadian PEDs. METHODS: Using a comparative case study design, we classified nine tertiary care pediatric hospital PEDs based on their stage of implementation. Data were collected using focus group interviews with physicians, registered nurses (RNs), and respiratory therapists (RTs), and individual interviews with both patient care and medical directors at each site. Initial coding was based on the Ottawa Model of Research Use (OMRU) categories of elements known to influence the uptake of innovations. RESULTS: One hundred and fifty healthcare professionals from nine different healthcare institutions participated in this study. Lack of leadership in the form of a research champion, a lack of consensus about the benefits of MDI/spacers among staff, perceived resistance from patients/parents, and perceived increased cost and workload associated with MDI/spacer use were the most prevalent barriers to the adoption of the MDI/spacer. Common strategies used by early-adopting sites included the active participation of all professional groups in the adoption process in addition to a well-planned and executed educational component for staff, patients, and families. Early adopter sites were also more likely to have the MDI/spacer included in a clinical protocol/pathway. CONCLUSION: Potential barriers and supports to implementation have been identified that will help EDs adopt MDI/spacer use. Future interventions intended to increase MDI/spacer use in PEDs will need to be sensitive to the barriers identified in this study.",2009 Oct 13,"['Scott, Shannon D', 'Osmond, Martin H', ""O'Leary, Kathy A"", 'Graham, Ian D', 'Grimshaw, Jeremy', 'Klassen, Terry', None]",Implement Sci,,,True
f8710043513b5790e20921e8a36d1cc94b402701,PMC,Analysis of virion associated host proteins in vesicular stomatitis virus using a proteomics approach,http://dx.doi.org/10.1186/1743-422X-6-166,PMC2770056,19821998,CC BY,"BACKGROUND: Vesicular stomatitis virus (VSV) is the prototypic rhabdovirus and the best studied member of the order Mononegavirales. There is now compelling evidence that enveloped virions released from infected cells carry numerous host (cellular) proteins some of which may play an important role in viral replication. Although several cellular proteins have been previously shown to be incorporated into VSV virions, no systematic study has been done to reveal the host protein composition for virions of VSV or any other member of Mononegavirales. RESULTS: Here we used a proteomics approach to identify cellular proteins within purified VSV virions, thereby creating a ""snapshot"" of one stage of virus/host interaction that can guide future experiments aimed at understanding molecular mechanisms of virus-cell interactions. Highly purified preparations of VSV virions from three different cell lines of human, mouse and hamster origin were analyzed for the presence of cellular proteins using mass spectrometry. We have successfully confirmed the presence of several previously-identified cellular proteins within VSV virions and identified a number of additional proteins likely to also be present within the virions. In total, sixty-four cellular proteins were identified, of which nine were found in multiple preparations. A combination of immunoblotting and proteinase K protection assay was used to verify the presence of several of these proteins (integrin β1, heat shock protein 90 kDa, heat shock cognate 71 kDa protein, annexin 2, elongation factor 1a) within the virions. CONCLUSION: This is, to our knowledge, the first systematic study of the host protein composition for virions of VSV or any other member of the order Mononegavirales. Future experiments are needed to determine which of the identified proteins have an interaction with VSV and whether these interactions are beneficial, neutral or antiviral with respect to VSV replication. Identification of host proteins-virus interactions beneficial for virus would be particularly exciting as they can provide new ways to combat viral infections via control of host components.",2009 Oct 12,"['Moerdyk-Schauwecker, Megan', 'Hwang, Sun-Il', 'Grdzelishvili, Valery Z']",Virol J,,,True
600e8fba699669f496224f1ab80caa3df030a77a,PMC,Using Dynamic Stochastic Modelling to Estimate Population Risk Factors in Infectious Disease: The Example of FIV in 15 Cat Populations,http://dx.doi.org/10.1371/journal.pone.0007377,PMC2770169,19888418,CC BY,"BACKGROUND: In natural cat populations, Feline Immunodeficiency Virus (FIV) is transmitted through bites between individuals. Factors such as the density of cats within the population or the sex-ratio can have potentially strong effects on the frequency of fight between individuals and hence appear as important population risk factors for FIV. METHODOLOGY/PRINCIPAL FINDINGS: To study such population risk factors, we present data on FIV prevalence in 15 cat populations in northeastern France. We investigate five key social factors of cat populations; the density of cats, the sex-ratio, the number of males and the mean age of males and females within the population. We overcome the problem of dependence in the infective status data using sexually-structured dynamic stochastic models. Only the age of males and females had an effect (p = 0.043 and p = 0.02, respectively) on the male-to-female transmission rate. Due to multiple tests, it is even likely that these effects are, in reality, not significant. Finally we show that, in our study area, the data can be explained by a very simple model that does not invoke any risk factor. CONCLUSION: Our conclusion is that, in host-parasite systems in general, fluctuations due to stochasticity in the transmission process are naturally very large and may alone explain a larger part of the variability in observed disease prevalence between populations than previously expected. Finally, we determined confidence intervals for the simple model parameters that can be used to further aid in management of the disease.",2009 Oct 16,"['Fouchet, David', 'Leblanc, Guillaume', 'Sauvage, Frank', 'Guiserix, Micheline', 'Poulet, Hervé', 'Pontier, Dominique']",PLoS One,,,True
f07550405043e5c3820e2c85a0b8003b64e8e163,PMC,Cleavage of the SARS Coronavirus Spike Glycoprotein by Airway Proteases Enhances Virus Entry into Human Bronchial Epithelial Cells In Vitro,http://dx.doi.org/10.1371/journal.pone.0007870,PMC2773421,19924243,CC BY,"BACKGROUND: Entry of enveloped viruses into host cells requires the activation of viral envelope glycoproteins through cleavage by either intracellular or extracellular proteases. In order to gain insight into the molecular basis of protease cleavage and its impact on the efficiency of viral entry, we investigated the susceptibility of a recombinant native full-length S-protein trimer (triSpike) of the severe acute respiratory syndrome coronavirus (SARS-CoV) to cleavage by various airway proteases. METHODOLOGY/PRINCIPAL FINDINGS: Purified triSpike proteins were readily cleaved in vitro by three different airway proteases: trypsin, plasmin and TMPRSS11a. High Performance Liquid Chromatography (HPLC) and amino acid sequencing analyses identified two arginine residues (R667 and R797) as potential protease cleavage site(s). The effect of protease-dependent enhancement of SARS-CoV infection was demonstrated with ACE2 expressing human bronchial epithelial cells 16HBE. Airway proteases regulate the infectivity of SARS-CoV in a fashion dependent on previous receptor binding. The role of arginine residues was further shown with mutant constructs (R667A, R797A or R797AR667A). Mutation of R667 or R797 did not affect the expression of S-protein but resulted in a differential efficacy of pseudotyping into SARS-CoVpp. The R667A SARS-CoVpp mutant exhibited a lack of virus entry enhancement following protease treatment. CONCLUSIONS/SIGNIFICANCE: These results suggest that SARS S-protein is susceptible to airway protease cleavage and, furthermore, that protease mediated enhancement of virus entry depends on specific conformation of SARS S-protein upon ACE2 binding. These data have direct implications for the cell entry mechanism of SARS-CoV along the respiratory system and, furthermore expand the possibility of identifying potential therapeutic agents against SARS-CoV.",2009 Nov 17,"['Kam, Yiu-Wing', 'Okumura, Yuushi', 'Kido, Hiroshi', 'Ng, Lisa F. P.', 'Bruzzone, Roberto', 'Altmeyer, Ralf']",PLoS One,,,True
4d0d82be6ba94422e252ff243a2cd89d13ea736a,PMC,MicroRNome Analysis Unravels the Molecular Basis of SARS Infection in Bronchoalveolar Stem Cells,http://dx.doi.org/10.1371/journal.pone.0007837,PMC2773932,19915717,CC BY,"Severe acute respiratory syndrome (SARS), caused by the coronavirus SARS-CoV, is an acute infectious disease with significant mortality. A typical clinical feature associated with SARS is pulmonary fibrosis and associated lung failure. In the aftermath of the SARS epidemic, although significant progress towards understanding the underlying molecular mechanism of the infection has been made, a large gap still remains in our knowledge regarding how SARS-CoV interacts with the host cell at the onset of infection. The rapidly changing viral genome adds another variable to this equation. We have focused on a novel concept of microRNA (miRNA)–mediated host–virus interactions in bronchoalveolar stem cells (BASCs) at the onset of infection by correlating the “BASC–microRNome” with their targets within BASCs and viral genome. This work encompasses miRNA array data analysis, target prediction, and miRNA–mRNA enrichment analysis and develops a complex interaction map among disease-related factors, miRNAs, and BASCs in SARS pathway, which will provide some clues for diagnostic markers to view an overall interplay leading to disease progression. Our observation reveals the BASCs (Sca-1+ CD34+ CD45- Pecam-), a subset of Oct-4+ ACE2+ epithelial colony cells at the broncho-alveolar duct junction, to be the prime target cells of SARS-CoV infection. Upregulated BASC miRNAs-17*, -574-5p, and -214 are co-opted by SARS-CoV to suppress its own replication and evade immune elimination until successful transmission takes place. Viral Nucleocapsid and Spike protein targets seem to co-opt downregulated miR-223 and miR-98 respectively within BASCs to control the various stages of BASC differentiation, activation of inflammatory chemokines, and downregulation of ACE2. All these effectively accounts for a successful viral transmission and replication within BASCs causing continued deterioration of lung tissues and apparent loss of capacity for lung repair. Overall, this investigation reveals another mode of exploitation of cellular miRNA machinery by virus to their own advantage.",2009 Nov 13,"['Mallick, Bibekanand', 'Ghosh, Zhumur', 'Chakrabarti, Jayprokas']",PLoS One,,,True
6efde6b65a96f7b14d75d637f5dd77f8e6e1c51c,PMC,Taipei's Use of a Multi-Channel Mass Risk Communication Program to Rapidly Reverse an Epidemic of Highly Communicable Disease,http://dx.doi.org/10.1371/journal.pone.0007962,PMC2776508,19956722,CC BY,"BACKGROUND: In September 2007, an outbreak of acute hemorrhagic conjunctivitis (AHC) occurred in Keelung City and spread to Taipei City. In response to the epidemic, a new crisis management program was implemented and tested in Taipei. METHODOLOGY AND PRINCIPAL FINDINGS: Having noticed that transmission surged on weekends during the Keelung epidemic, Taipei City launched a multi-channel mass risk communications program that included short message service (SMS) messages sent directly to approximately 2.2 million Taipei residents on Friday, October 12th, 2007. The public was told to keep symptomatic students from schools and was provided guidelines for preventing the spread of the disease at home. Epidemiological characteristics of Taipei's outbreak were analyzed from 461 sampled AHC cases. Median time from exposure to onset of the disease was 1 day. This was significantly shorter for cases occurring in family clusters than in class clusters (mean±SD: 2.6±3.2 vs. 4.39±4.82 days, p = 0.03), as well as for cases occurring in larger family clusters as opposed to smaller ones (1.2±1.7 days vs. 3.9±4.0 days, p<0.01). Taipei's program had a significant impact on patient compliance. Home confinement of symptomatic children increased from 10% to 60% (p<0.05) and helped curb the spread of AHC. Taipei experienced a rapid decrease in AHC cases between the Friday of the SMS announcement and the following Monday, October 15, (0.70% vs. 0.36%). By October 26, AHC cases reduced to 0.01%. The success of this risk communication program in Taipei (as compared to Keelung) is further reflected through rapid improvements in three epidemic indicators: (1) significantly lower crude attack rates (1.95% vs. 14.92%, p<0.001), (2) a short epidemic period of AHC (13 vs. 34 days), and (3) a quick drop in risk level (1∼2 weeks) in Taipei districts that border Keelung (the original domestic epicenter). CONCLUSIONS AND SIGNIFICANCE: The timely launch of this systematic, communication-based intervention proved effective at preventing a dangerous spike in AHC and was able to bring this high-risk disease under control. We recommend that public health officials incorporate similar methods into existing guidelines for preventing pandemic influenza and other emerging infectious diseases.",2009 Nov 23,"['Yen, Muh-Yong', 'Wu, Tsung-Shu Joseph', 'Chiu, Allen Wen-Hsiang', 'Wong, Wing-Wai', 'Wang, Po-En', 'Chan, Ta-Chien', 'King, Chwan-Chuen']",PLoS One,,,True
095bdb615ea39929bf971754be5f9250d327cfb5,PMC,Taipei's Use of a Multi-Channel Mass Risk Communication Program to Rapidly Reverse an Epidemic of Highly Communicable Disease,http://dx.doi.org/10.1371/journal.pone.0007962,PMC2776508,19956722,CC BY,"BACKGROUND: In September 2007, an outbreak of acute hemorrhagic conjunctivitis (AHC) occurred in Keelung City and spread to Taipei City. In response to the epidemic, a new crisis management program was implemented and tested in Taipei. METHODOLOGY AND PRINCIPAL FINDINGS: Having noticed that transmission surged on weekends during the Keelung epidemic, Taipei City launched a multi-channel mass risk communications program that included short message service (SMS) messages sent directly to approximately 2.2 million Taipei residents on Friday, October 12th, 2007. The public was told to keep symptomatic students from schools and was provided guidelines for preventing the spread of the disease at home. Epidemiological characteristics of Taipei's outbreak were analyzed from 461 sampled AHC cases. Median time from exposure to onset of the disease was 1 day. This was significantly shorter for cases occurring in family clusters than in class clusters (mean±SD: 2.6±3.2 vs. 4.39±4.82 days, p = 0.03), as well as for cases occurring in larger family clusters as opposed to smaller ones (1.2±1.7 days vs. 3.9±4.0 days, p<0.01). Taipei's program had a significant impact on patient compliance. Home confinement of symptomatic children increased from 10% to 60% (p<0.05) and helped curb the spread of AHC. Taipei experienced a rapid decrease in AHC cases between the Friday of the SMS announcement and the following Monday, October 15, (0.70% vs. 0.36%). By October 26, AHC cases reduced to 0.01%. The success of this risk communication program in Taipei (as compared to Keelung) is further reflected through rapid improvements in three epidemic indicators: (1) significantly lower crude attack rates (1.95% vs. 14.92%, p<0.001), (2) a short epidemic period of AHC (13 vs. 34 days), and (3) a quick drop in risk level (1∼2 weeks) in Taipei districts that border Keelung (the original domestic epicenter). CONCLUSIONS AND SIGNIFICANCE: The timely launch of this systematic, communication-based intervention proved effective at preventing a dangerous spike in AHC and was able to bring this high-risk disease under control. We recommend that public health officials incorporate similar methods into existing guidelines for preventing pandemic influenza and other emerging infectious diseases.",2009 Nov 23,"['Yen, Muh-Yong', 'Wu, Tsung-Shu Joseph', 'Chiu, Allen Wen-Hsiang', 'Wong, Wing-Wai', 'Wang, Po-En', 'Chan, Ta-Chien', 'King, Chwan-Chuen']",PLoS One,,,False
6507acff69dc9963ee7fdffc4a7f4edae0b5f609,PMC,Experimental infection in calves with a specific subtype of verocytotoxin-producing Escherichia coli O157:H7 of bovine origin,http://dx.doi.org/10.1186/1751-0147-51-43,PMC2776595,19878595,CC BY,"BACKGROUND: In Sweden, a particular subtype of verocytotoxin-producing Escherichia coli (VTEC) O157:H7, originally defined as being of phage type 4, and carrying two vtx(2 )genes, has been found to cause the majority of reported human infections during the past 15 years, including both sporadic cases and outbreaks. One plausible explanation for this could be that this particular subtype is better adapted to colonise cattle, and thereby may be excreted in greater concentrations and for longer periods than other VTEC O157:H7 subtypes. METHODS: In an experimental study, 4 calves were inoculated with 10(9 )colony forming units (cfu) of strain CCUG 53931, representative of the subtype VTEC O157:H7 (PT4;vtx(2);vtx(2c)). Two un-inoculated calves were co-housed with the inoculated calves. Initially, the VTEC O157:H7 strain had been isolated from a dairy herd with naturally occurring infection and the farm had previously also been linked to human infection with the same strain. Faecal samples were collected over up to a 2-month period and analysed for VTEC O157 by immuno-magnetic separation (IMS), and IMS positive samples were further analysed by direct plating to elucidate the shedding pattern. Samples were also collected from the pharynx. RESULTS: All inoculated calves proved culture-positive in faeces within 24 hours after inoculation and the un-inoculated calves similarly on days 1 and 3 post-inoculation. One calf was persistently culture-positive for 43 days; in the remainder, the VTEC O157:H7 count in faeces decreased over the first 2 weeks. All pharyngeal samples were culture-negative for VTEC O157:H7. CONCLUSION: This study contributes with information concerning the dynamics of a specific subtype of VTEC O157:H7 colonisation in dairy calves. This subtype, VTEC O157:H7 (PT4;vtx(2;)vtx(2c)), is frequently isolated from Swedish cattle and has also been found to cause the majority of reported human infections in Sweden during the past 15 years. In most calves, inoculated with a representative strain of this specific subtype, the numbers of shed bacteria declined over the first two weeks. One calf could possibly be classified as a high-shedder, excreting high levels of the bacterium for a prolonged period.",2009 Oct 31,"['Jonsson, Malin E', 'Eriksson, Erik', 'Boqvist, Sofia', 'Urdahl, Anne Margrete', 'Aspán, Anna']",Acta Vet Scand,,,True
28cfe86a8fa13dacd3f447dcb095ac9a9f99a33a,PMC,Immunoglobulin Superfamily Virus Receptors and the Evolution of Adaptive Immunity,http://dx.doi.org/10.1371/journal.ppat.1000481,PMC2777377,19956667,CC BY,,2009 Nov 26,"['Dermody, Terence S.', 'Kirchner, Eva', 'Guglielmi, Kristen M.', 'Stehle, Thilo']",PLoS Pathog,,,True
10829aeda495398ba475afbd713e36bdc58cfcd0,PMC,Peptide-Mediated Cellular Delivery of Oligonucleotide-Based Therapeutics In Vitro: Quantitative Evaluation of Overall Efficacy Employing Easy to Handle Reporter Systems,http://dx.doi.org/10.2174/138161208786898806,PMC2778081,19075740,CC BY,"Cellular uptake of therapeutic oligonucleotides and subsequent intracellular trafficking to their target sites represents the major technical hurdle for the biological effectiveness of these potential drugs. Accordingly, laboratories worldwide focus on the development of suitable delivery systems. Among the different available non-viral systems like cationic polymers, cationic liposomes and polymeric nanoparticles, cell-penetrating peptides (CPPs) represent an attractive concept to bypass the problem of poor membrane permeability of these charged macromolecules. While uptake per se in most cases does not represent the main obstacle of nucleic acid delivery in vitro, it becomes increasingly apparent that intracellular trafficking is the bottleneck. As a consequence, in order to optimize a given delivery system, a side-by-side analysis of nucleic acid cargo internalized and the corresponding biological effect is required to determine the overall efficacy. In this review, we will concentrate on peptide-mediated delivery of siRNAs and steric block oligonucleotides and discuss different methods for quantitative assessment of the amount of cargo taken up and how to correlate those numbers with biological effects by applying easy to handle reporter systems. To illustrate current limitations of non-viral nucleic acid delivery systems, we present own data as an example and discuss options of how to enhance trafficking of molecules entrapped in cellular compartments.",2008 Dec,"['Laufer, S.D', 'Restle, T']",Curr Pharm Des,,,True
75cc9a3d0d2fc4baea735c4090944046019c8d39,PMC,"A Novel Enediynyl Peptide Inhibitor of Furin That Blocks Processing of proPDGF-A, B and proVEGF-C",http://dx.doi.org/10.1371/journal.pone.0007700,PMC2778948,19956642,CC BY,"BACKGROUND: Furin represents a crucial member of secretory mammalian subtilase, the Proprotein Convertase (PC) or Proprotein Convertase Subtilisin/Kexin (PCSK) superfamily. It has been linked to cancer, tumorgenesis, viral and bacterial pathogenesis. As a result it is considered a major target for intervention of these diseases. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we report, for the first time, the synthesis and biological evaluation of a newly designed potent furin inhibitor that contains a highly reactive beta-turn inducing and radical generating “enediynyl amino acid” (Eda) moiety. “Eda” was inserted between P1 and P1′ residues of hfurin(98–112) peptide, derived from the primary cleavage site of furin's own prodomain. The resulting hexadecapeptide derivative inhibited furin in vitro with IC(50) ∼40 nM when measured against the fluorogenic substrate Boc-RVRR-MCA. It also inhibited furin-mediated cleavage of a fluorogenic peptide derived from hSARS-CoV spike protein with IC(50) ∼193 nM. Additionally it also blocked furin-processing of growth factors proPDGF-A, B and VEGF-C that are linked to tumor genesis and cancer. Circular dichroism study showed that this inhibitor displayed a predominantly beta-turn structure while western blots confirmed its ability to protect furin protein from self degradation. CONCLUSION/SIGNIFICANCE: These findings imply its potential as a therapeutic agent for intervention of cancer and other furin-associated diseases.",2009 Nov 26,"['Basak, Ajoy', 'Khatib, Abdel-Majid', 'Mohottalage, Dayani', 'Basak, Sarmistha', 'Kolajova, Maria', 'Bag, Subhendu Sekhar', 'Basak, Amit']",PLoS One,,,True
7384db26f7f0a5f8c75844b2225b1783e6d783e5,PMC,"Human pregnancy-associated malaria-specific B cells target polymorphic, conformational epitopes in VAR2CSA",http://dx.doi.org/10.1111/j.1365-2958.2006.05503.x,PMC2779471,17176260,CC BY,"Pregnancy-associated malaria (PAM) is caused by Plasmodium falciparum-infected erythrocytes (IEs) that bind to chondroitin sulphate A (CSA) in the placenta by PAM-associated clonally variant surface antigens (VSA). Pregnancy-specific VSA (VSA(PAM)), which include the PfEMP1 variant VAR2CSA, are targets of IgG-mediated protective immunity to PAM. Here, we report an investigation of the specificity of naturally acquired immunity to PAM, using eight human monoclonal IgG1 antibodies that react exclusively with intact CSA-adhering IEs expressing VSA(PAM). Four reacted in Western blotting with high-molecular-weight (> 200 kDa) proteins, while seven reacted with either the DBL3-X or the DBL5-ε domains of VAR2CSA expressed either as Baculovirus constructs or on the surface of transfected Jurkat cells. We used a panel of recombinant antigens representing DBL3-X domains from P. falciparum field isolates to evaluate B-cell epitope diversity among parasite isolates, and identified the binding site of one monoclonal antibody using a chimeric DBL3-X construct. Our findings show that there is a high-frequency memory response to VSA(PAM), indicating that VAR2CSA is a primary target of naturally acquired PAM-specific protective immunity, and demonstrate the value of human monoclonal antibodies and conformationally intact recombinant antigens in VSA characterization.",2007 Jan,"['Barfod, Lea', 'Bernasconi, Nadia L', 'Dahlbäck, Madeleine', 'Jarrossay, David', 'Andersen, Pernille Haste', 'Salanti, Ali', 'Ofori, Michael F', 'Turner, Louise', 'Resende, Mafalda', 'Nielsen, Morten A', 'Theander, Thor G', 'Sallusto, Federica', 'Lanzavecchia, Antonio', 'Hviid, Lars']",Mol Microbiol,,,True
957ab1fcf790e8dd9d681f1f216287db1177cb78,PMC,Mathematical epidemiology is not an oxymoron,http://dx.doi.org/10.1186/1471-2458-9-S1-S2,PMC2779504,19922686,CC BY,"A brief description of the importance of communicable diseases in history and the development of mathematical modelling of disease transmission is given. This includes reasons for mathematical modelling, the history of mathematical modelling from the foundations laid in the late nineteenth century to the present, some of the accomplishments of mathematical modelling, and some challenges for the future. Our purpose is to demonstrate the importance of mathematical modelling for the understanding and management of infectious disease transmission.",2009 Nov 18,"Brauer, Fred",BMC Public Health,,,True
076d18c2ee294256a400299b5c4631aac187d47a,PMC,Early Assessment of Anxiety and Behavioral Response to Novel Swine-Origin Influenza A(H1N1),http://dx.doi.org/10.1371/journal.pone.0008032,PMC2779851,19997505,CC BY,"BACKGROUND: Since late April, 2009, a novel influenza virus A (H1N1), generally referred to as the “swine flu,” has spread around the globe and infected hundreds of thousands of people. During the first few days after the initial outbreak in Mexico, extensive media coverage together with a high degree of uncertainty about the transmissibility and mortality rate associated with the virus caused widespread concern in the population. The spread of an infectious disease can be strongly influenced by behavioral changes (e.g., social distancing) during the early phase of an epidemic, but data on risk perception and behavioral response to a novel virus is usually collected with a substantial delay or after an epidemic has run its course. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the results from an online survey that gathered data (n = 6,249) about risk perception of the Influenza A(H1N1) outbreak during the first few days of widespread media coverage (April 28 - May 5, 2009). We find that after an initially high level of concern, levels of anxiety waned along with the perception of the virus as an immediate threat. Overall, our data provide evidence that emotional status mediates behavioral response. Intriguingly, principal component analysis revealed strong clustering of anxiety about swine flu, bird flu and terrorism. All three of these threats receive a great deal of media attention and their fundamental uncertainty is likely to generate an inordinate amount of fear vis-a-vis their actual threat. CONCLUSIONS/SIGNIFICANCE: Our results suggest that respondents' behavior varies in predictable ways. Of particular interest, we find that affective variables, such as self-reported anxiety over the epidemic, mediate the likelihood that respondents will engage in protective behavior. Understanding how protective behavior such as social distancing varies and the specific factors that mediate it may help with the design of epidemic control strategies.",2009 Dec 3,"['Jones, James Holland', 'Salathé, Marcel']",PLoS One,,,True
53c533539d95b75bb8f88fe08e4693f299fd116e,PMC,Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells,http://dx.doi.org/10.1186/1465-9921-10-102,PMC2780994,19874627,CC BY,"BACKGROUND: Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. AIM: To study influenza A (H5N1) virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. METHODS: We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. RESULTS: We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our data suggests that viremia, secondary to, for example, gastro-intestinal infection, can potentially lead to infection of the lung. HPAI H5N1 virus was a more potent inducer of cytokines (e.g. IP-10, RANTES, IL-6) in comparison to H1N1 virus in alveolar epithelial cells, and these virus-induced chemokines were secreted onto both the apical and basolateral aspects of the polarized alveolar epithelium. CONCLUSION: The predilection of viruses for different routes of entry and egress from the infected cell is important in understanding the pathogenesis of influenza H5N1 infection and may help unravel the pathogenesis of human H5N1 disease.",2009 Oct 30,"['Chan, Michael CW', 'Chan, Renee WY', 'Yu, Wendy CL', 'Ho, Carol CC', 'Chui, WH', 'Lo, CK', 'Yuen, Kit M', 'Guan, Yi', 'Nicholls, John M', 'Peiris, JS Malik']",Respir Res,,,True
4961ab3b26b0165a3f1b267fc776329d792fc5f2,PMC,Comparison of distance measures in spatial analytical modeling for health service planning,http://dx.doi.org/10.1186/1472-6963-9-200,PMC2781002,19895692,CC BY,"BACKGROUND: Several methodological approaches have been used to estimate distance in health service research. In this study, focusing on cardiac catheterization services, Euclidean, Manhattan, and the less widely known Minkowski distance metrics are used to estimate distances from patient residence to hospital. Distance metrics typically produce less accurate estimates than actual measurements, but each metric provides a single model of travel over a given network. Therefore, distance metrics, unlike actual measurements, can be directly used in spatial analytical modeling. Euclidean distance is most often used, but unlikely the most appropriate metric. Minkowski distance is a more promising method. Distances estimated with each metric are contrasted with road distance and travel time measurements, and an optimized Minkowski distance is implemented in spatial analytical modeling. METHODS: Road distance and travel time are calculated from the postal code of residence of each patient undergoing cardiac catheterization to the pertinent hospital. The Minkowski metric is optimized, to approximate travel time and road distance, respectively. Distance estimates and distance measurements are then compared using descriptive statistics and visual mapping methods. The optimized Minkowski metric is implemented, via the spatial weight matrix, in a spatial regression model identifying socio-economic factors significantly associated with cardiac catheterization. RESULTS: The Minkowski coefficient that best approximates road distance is 1.54; 1.31 best approximates travel time. The latter is also a good predictor of road distance, thus providing the best single model of travel from patient's residence to hospital. The Euclidean metric and the optimal Minkowski metric are alternatively implemented in the regression model, and the results compared. The Minkowski method produces more reliable results than the traditional Euclidean metric. CONCLUSION: Road distance and travel time measurements are the most accurate estimates, but cannot be directly implemented in spatial analytical modeling. Euclidean distance tends to underestimate road distance and travel time; Manhattan distance tends to overestimate both. The optimized Minkowski distance partially overcomes their shortcomings; it provides a single model of travel over the network. The method is flexible, suitable for analytical modeling, and more accurate than the traditional metrics; its use ultimately increases the reliability of spatial analytical models.",2009 Nov 6,"['Shahid, Rizwan', 'Bertazzon, Stefania', 'Knudtson, Merril L', 'Ghali, William A']",BMC Health Serv Res,,,True
ad898b084d41c346f3da45e58960ae7925d52100,PMC,Influenza in Africa,http://dx.doi.org/10.1371/journal.pmed.1000182,PMC2782135,20016686,CC BY,"Maria Yazdanbakhsh and Peter Kremsner argue that there needs to be better awareness, surveillance, and clinical management of common febrile diseases in Africa, especially influenza.",2009 Dec 15,"['Yazdanbakhsh, Maria', 'Kremsner, Peter G.']",PLoS Med,,,True
2cbb038739adbd4487fa3c529e404189637e59d4,PMC,Rapid detection of ERG11 gene mutations in clinical Candida albicans isolates with reduced susceptibility to fluconazole by rolling circle amplification and DNA sequencing,http://dx.doi.org/10.1186/1471-2180-9-167,PMC2782262,19682357,CC BY,"BACKGROUND: Amino acid substitutions in the target enzyme Erg11p of azole antifungals contribute to clinically-relevant azole resistance in Candida albicans. A simple molecular method for rapid detection of ERG11 gene mutations would be an advantage as a screening tool to identify potentially-resistant strains and to track their movement. To complement DNA sequencing, we developed a padlock probe and rolling circle amplification (RCA)-based method to detect a series of mutations in the C. albicans ERG11 gene using ""reference"" azole-resistant isolates with known mutations. The method was then used to estimate the frequency of ERG11 mutations and their type in 25 Australian clinical C. albicans isolates with reduced susceptibility to fluconazole and in 23 fluconazole-susceptible isolates. RCA results were compared DNA sequencing. RESULTS: The RCA assay correctly identified all ERG11 mutations in eight ""reference"" C. albicans isolates. When applied to 48 test strains, the RCA method showed 100% agreement with DNA sequencing where an ERG11 mutation-specific probe was used. Of 20 different missense mutations detected by sequencing in 24 of 25 (96%) isolates with reduced fluconazole susceptibility, 16 were detected by RCA. Five missense mutations were detected by both methods in 18 of 23 (78%) fluconazole-susceptible strains. DNA sequencing revealed that mutations in non-susceptible isolates were all due to homozygous nucleotide changes. With the exception of the mutations leading to amino acid substitution E266D, those in fluconazole-susceptible strains were heterozygous. Amino acid substitutions common to both sets of isolates were D116E, E266D, K128T, V437I and V488I. Substitutions unique to isolates with reduced fluconazole susceptibility were G464 S (n = 4 isolates), G448E (n = 3), G307S (n = 3), K143R (n = 3) and Y123H, S405F and R467K (each n = 1). DNA sequencing revealed a novel substitution, G450V, in one isolate. CONCLUSION: The sensitive RCA assay described here is a simple, robust and rapid (2 h) method for the detection of ERG11 polymorphisms. It showed excellent concordance with ERG11 sequencing and is a potentially valuable tool to track the emergence and spread of azole-resistant C. albicans and to study the epidemiology of ERG11 mutations. The RCA method is applicable to the study of azole resistance in other fungi.",2009 Aug 14,"['Wang, Huiping', 'Kong, Fanrong', 'Sorrell, Tania C', 'Wang, Bin', 'McNicholas, Paul', 'Pantarat, Namfon', 'Ellis, David', 'Xiao, Meng', 'Widmer, Fred', 'Chen, Sharon CA']",BMC Microbiol,,,True
41c7a01f11ed47591d99f45774e43e45aeba0619,PMC,CAPIH: A Web interface for comparative analyses and visualization of host-HIV protein-protein interactions,http://dx.doi.org/10.1186/1471-2180-9-164,PMC2782265,19674441,CC BY,"BACKGROUND: The Human Immunodeficiency Virus type one (HIV-1) is the major causing pathogen of the Acquired Immune Deficiency Syndrome (AIDS). A large number of HIV-1-related studies are based on three non-human model animals: chimpanzee, rhesus macaque, and mouse. However, the differences in host-HIV-1 interactions between human and these model organisms have remained unexplored. DESCRIPTION: Here we present CAPIH (Comparative Analysis of Protein Interactions for HIV-1), the first web-based interface to provide comparative information between human and the three model organisms in the context of host-HIV-1 protein interactions. CAPIH identifies genetic changes that occur in HIV-1-interacting host proteins. In a total of 1,370 orthologous protein sets, CAPIH identifies ~86,000 amino acid substitutions, ~21,000 insertions/deletions, and ~33,000 potential post-translational modifications that occur only in one of the four compared species. CAPIH also provides an interactive interface to display the host-HIV-1 protein interaction networks, the presence/absence of orthologous proteins in the model organisms in the networks, the genetic changes that occur in the protein nodes, and the functional domains and potential protein interaction hot sites that may be affected by the genetic changes. The CAPIH interface is freely accessible at http://bioinfo-dbb.nhri.org.tw/capih. CONCLUSION: CAPIH exemplifies that large divergences exist in disease-associated proteins between human and the model animals. Since all of the newly developed medications must be tested in model animals before entering clinical trials, it is advisable that comparative analyses be performed to ensure proper translations of animal-based studies. In the case of AIDS, the host-HIV-1 protein interactions apparently have differed to a great extent among the compared species. An integrated protein network comparison among the four species will probably shed new lights on AIDS studies.",2009 Aug 12,"['Lin, Fan-Kai', 'Pan, Chia-Lin', 'Yang, Jinn-Moon', 'Chuang, Trees-Juen', 'Chen, Feng-Chi']",BMC Microbiol,,,True
1638100b254164ee9af7d66be61794a7efa07b78,PMC,Pulmonary fibrosis induced by H5N1 viral infection in mice,http://dx.doi.org/10.1186/1465-9921-10-107,PMC2783028,19909524,CC BY,"BACKGROUND: Inflammatory process results in lung injury that may lead to pulmonary fibrosis (PF). Here, we described PF in mice infected with H5N1 virus. METHODS: Eight-week-old BALB/c mice were inoculated intranasally with 1 × 10(1 )MID(50 )of A/Chicken/Hebei/108/2002(H5N1) viruses. Lung injury/fibrosis was evaluated by observation of hydroxyproline concentrations, lung indexes, and histopathology on days 7, 14, and 30 postinoculation. RESULTS: H5N1-inoculated mice presented two stages of pulmonary disease over a 30-d period after infection. At acute stage, infected-mice showed typical diffuse pneumonia with inflammatory cellular infiltration, alveolar and interstitial edema and hemorrhage on day 7 postinoculation. At restoration stage, most infected-mice developed PF of different severities on day 30 postinoculation, and 18% of the survived mice underwent severe interstitial and intra-alveolar fibrosis with thickened alveolar walls, collapsed alveoli and large fibrotic areas. The dramatically elevated hydroxyproline levels in H5N1-infected mice showed deposition of collagen in lungs, and confirmed fibrosis of lungs. The dry lung-to-body weight ratio was significantly increased in infected group, which might be associated with the formation of PF in H5N1-infected mice. CONCLUSION: Our findings show that H5N1-infected mice develop the typical PF during restoration period, which will contribute to the investigation of fibrogenesis and potential therapeutic intervention in human H5N1 disease.",2009 Nov 12,"['Qiao, Jian', 'Zhang, Miaojie', 'Bi, Jianmin', 'Wang, Xun', 'Deng, Guangcun', 'He, Guimei', 'Luan, Zhihua', 'Lv, Nana', 'Xu, Tong', 'Zhao, Lihong']",Respir Res,,,True
513a25eb7a96ba7f7ae433498caf4791eb19e97c,PMC,Apolipoprotein D in Lipid Metabolism and Its Functional Implication in Atherosclerosis and Aging,,PMC2784685,19946382,CC BY,"Dyslipidemia is characterized by increased triglyceride and low-density lipoprotein (LDL) levels, and decreased high-density lipoprotein (HDL) levels. Such an atherogenic lipid profile often predisposes an at risk individual to coronary artery disease with incompletely understood mechanisms. Apolipoprotein D (apoD) is an atypical apolipoprotein. Unlike canonical apolipoproteins that are produced mainly in liver and intestine, apoD is expressed widely in mammalian tissues. ApoD does not share significant degrees of homology in amino acid sequence with other apolipoproteins. Instead, apoD is structurally similar to lipocalins, a diverse family of lipid-binding proteins that are responsible for transporting lipids and other small hydrophobic molecules for metabolism. Plasma ApoD is present mainly in HDL and to a lesser extent in low density lipoproteins (LDL) and very low-density lipoproteins (VLDL). Genetic variants of apoD are associated with abnormal lipid metabolism and increased risk of developing metabolic syndrome. Increased apoD deposition is detectable in atherosclerotic lesions of humans with established cardiovascular disease as well as mice with premature atherosclerosis. Moreover, apoD is associated with anti-oxidation and anti-stress activities, contributing to lifespan expansion in fruit flies. Elderly subjects and patients with Alzheimer exhibit markedly elevated apoD production in the brain. Thus, apoD is emerged as a significant player in lipid metabolism and aging. Here we focus our review on recent advances toward our understanding of apoD in lipid metabolism and address whether apoD dysregulation contributes to the pathogenesis of dyslipidemia and atherosclerosis. We will also discuss the functional implication of apoD in aging.",2008 Dec 12,"['Perdomo, German', 'Dong, H. Henry']",Aging (Albany NY),,,True
da867b3ea92b5191c4fbdc4d09c0712a73da7766,PMC,A “One Health” Approach to Address Emerging Zoonoses: The HALI Project in Tanzania,http://dx.doi.org/10.1371/journal.pmed.1000190,PMC2784942,20016689,CC BY,"Jonna Mazet and colleagues describe their work in the Tanzania-based HALI Project, which adopts the “One Health” approach to address emerging zoonoses and that recognizes the interconnectedness of human, animal, and environmental health.",2009 Dec 15,"['Mazet, Jonna A. K.', 'Clifford, Deana L.', 'Coppolillo, Peter B.', 'Deolalikar, Anil B.', 'Erickson, Jon D.', 'Kazwala, Rudovick R.']",PLoS Med,,,True
57694e4ef5e2af0338dc7ba54cf154b2b0cdda76,PMC,Automated vocabulary discovery for geo-parsing online epidemic intelligence,http://dx.doi.org/10.1186/1471-2105-10-385,PMC2787530,19930702,CC BY,"BACKGROUND: Automated surveillance of the Internet provides a timely and sensitive method for alerting on global emerging infectious disease threats. HealthMap is part of a new generation of online systems designed to monitor and visualize, on a real-time basis, disease outbreak alerts as reported by online news media and public health sources. HealthMap is of specific interest for national and international public health organizations and international travelers. A particular task that makes such a surveillance useful is the automated discovery of the geographic references contained in the retrieved outbreak alerts. This task is sometimes referred to as ""geo-parsing"". A typical approach to geo-parsing would demand an expensive training corpus of alerts manually tagged by a human. RESULTS: Given that human readers perform this kind of task by using both their lexical and contextual knowledge, we developed an approach which relies on a relatively small expert-built gazetteer, thus limiting the need of human input, but focuses on learning the context in which geographic references appear. We show in a set of experiments, that this approach exhibits a substantial capacity to discover geographic locations outside of its initial lexicon. CONCLUSION: The results of this analysis provide a framework for future automated global surveillance efforts that reduce manual input and improve timeliness of reporting.",2009 Nov 24,"['Keller, Mikaela', 'Freifeld, Clark C', 'Brownstein, John S']",BMC Bioinformatics,,,True
08e78c0222e84457195ccefb2e371f1847670436,PMC,"Establishment, Immortalisation and Characterisation of Pteropid Bat Cell Lines",http://dx.doi.org/10.1371/journal.pone.0008266,PMC2788226,20011515,CC BY,"BACKGROUND: Bats are the suspected natural reservoir hosts for a number of new and emerging zoonotic viruses including Nipah virus, Hendra virus, severe acute respiratory syndrome coronavirus and Ebola virus. Since the discovery of SARS-like coronaviruses in Chinese horseshoe bats, attempts to isolate a SL-CoV from bats have failed and attempts to isolate other bat-borne viruses in various mammalian cell lines have been similarly unsuccessful. New stable bat cell lines are needed to help with these investigations and as tools to assist in the study of bat immunology and virus-host interactions. METHODOLOGY/FINDINGS: Black flying foxes (Pteropus alecto) were captured from the wild and transported live to the laboratory for primary cell culture preparation using a variety of different methods and culture media. Primary cells were successfully cultured from 20 different organs. Cell immortalisation can occur spontaneously, however we used a retroviral system to immortalise cells via the transfer and stable production of the Simian virus 40 Large T antigen and the human telomerase reverse transcriptase protein. Initial infection experiments with both cloned and uncloned cell lines using Hendra and Nipah viruses demonstrated varying degrees of infection efficiency between the different cell lines, although it was possible to infect cells in all tissue types. CONCLUSIONS/SIGNIFICANCE: The approaches developed and optimised in this study should be applicable to bats of other species. We are in the process of generating further cell lines from a number of different bat species using the methodology established in this study.",2009 Dec 11,"['Crameri, Gary', 'Todd, Shawn', 'Grimley, Samantha', 'McEachern, Jennifer A.', 'Marsh, Glenn A.', 'Smith, Craig', 'Tachedjian, Mary', 'De Jong, Carol', 'Virtue, Elena R.', 'Yu, Meng', 'Bulach, Dieter', 'Liu, Jun-Ping', 'Michalski, Wojtek P.', 'Middleton, Deborah', 'Field, Hume E.', 'Wang, Lin-Fa']",PLoS One,,,True
3799479a8ad2b8db9f21c68f88dfae6410d0fed0,PMC,A comprehensive assessment of N-terminal signal peptides prediction methods,http://dx.doi.org/10.1186/1471-2105-10-S15-S2,PMC2788353,19958512,CC BY,"BACKGROUND: Amino-terminal signal peptides (SPs) are short regions that guide the targeting of secretory proteins to the correct subcellular compartments in the cell. They are cleaved off upon the passenger protein reaching its destination. The explosive growth in sequencing technologies has led to the deposition of vast numbers of protein sequences necessitating rapid functional annotation techniques, with subcellular localization being a key feature. Of the myriad software prediction tools developed to automate the task of assigning the SP cleavage site of these new sequences, we review here, the performance and reliability of commonly used SP prediction tools. RESULTS: The available signal peptide data has been manually curated and organized into three datasets representing eukaryotes, Gram-positive and Gram-negative bacteria. These datasets are used to evaluate thirteen prediction tools that are publicly available. SignalP (both the HMM and ANN versions) maintains consistency and achieves the best overall accuracy in all three benchmarking experiments, ranging from 0.872 to 0.914 although other prediction tools are narrowing the performance gap. CONCLUSION: The majority of the tools evaluated in this study encounter no difficulty in discriminating between secretory and non-secretory proteins. The challenge clearly remains with pinpointing the correct SP cleavage site. The composite scoring schemes employed by SignalP may help to explain its accuracy. Prediction task is divided into a number of separate steps, thus allowing each score to tackle a particular aspect of the prediction.",2009 Dec 3,"['Choo, Khar Heng', 'Tan, Tin Wee', 'Ranganathan, Shoba']",BMC Bioinformatics,,,True
30f0103086a7458f1bdb18024f372814d88a9b4e,PMC,Efficient Assembly and Secretion of Recombinant Subviral Particles of the Four Dengue Serotypes Using Native prM and E Proteins,http://dx.doi.org/10.1371/journal.pone.0008325,PMC2790604,20016834,CC BY,"BACKGROUND: Flavivirus infected cells produce infectious virions and subviral particles, both of which are formed by the assembly of prM and E envelope proteins and are believed to undergo the same maturation process. Dengue recombinant subviral particles have been produced in cell cultures with either modified or chimeric proteins but not using the native forms of prM and E. METHODOLOGY/PRINCIPAL FINDINGS: We have used a codon optimization strategy to obtain an efficient expression of native viral proteins and production of recombinant subviral particles (RSPs) for all four dengue virus (DV) serotypes. A stable HeLa cell line expressing DV1 prME was established (HeLa-prME) and RSPs were analyzed by immunofluorescence and transmission electron microscopy. We found that E protein is mainly present in the endoplasmic reticulum (ER) where assembly of RSPs could be observed. Biochemical characterization of DV1 RSPs secretion revealed both prM protein cleavage and homodimerization of E proteins before their release into the supernatant, indicating that RSPs undergo a similar maturation process as dengue virus. Pulse chase experiment showed that 8 hours are required for the secretion of DV1 RSPs. We have used HeLa-prME to develop a semi-quantitative assay and screened a human siRNA library targeting genes involved in membrane trafficking. Knockdown of 23 genes resulted in a significant reduction in DV RSP secretion, whereas for 22 others we observed an increase of RSP levels in cell supernatant. CONCLUSIONS/SIGNIFICANCE: Our data describe the efficient production of RSPs containing native prM and E envelope proteins for all dengue serotypes. Dengue RSPs and corresponding producing cell lines are safe and novel tools that can be used in the study of viral egress as well as in the development of vaccine and drugs against dengue virus.",2009 Dec 15,"['Wang, Pei-Gang', 'Kudelko, Mateusz', 'Lo, Joanne', 'Siu, Lewis Yu Lam', 'Kwok, Kevin Tsz Hin', 'Sachse, Martin', 'Nicholls, John M.', 'Bruzzone, Roberto', 'Altmeyer, Ralf M.', 'Nal, Béatrice']",PLoS One,,,True
8e4a1132b0301964add6af40ca83b222d7f6d9e3,PMC,Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments,http://dx.doi.org/10.1371/journal.pone.0008326,PMC2790605,20016835,CC BY,"The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.",2009 Dec 16,"['Zhao, Huabin', 'Ru, Binghua', 'Teeling, Emma C.', 'Faulkes, Christopher G.', 'Zhang, Shuyi', 'Rossiter, Stephen J.']",PLoS One,,,True
a3b545a34bc8511e9c5fd6ff71443e92bd6cc915,PMC,Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments,http://dx.doi.org/10.1371/journal.pone.0008326,PMC2790605,20016835,CC BY,"The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.",2009 Dec 16,"['Zhao, Huabin', 'Ru, Binghua', 'Teeling, Emma C.', 'Faulkes, Christopher G.', 'Zhang, Shuyi', 'Rossiter, Stephen J.']",PLoS One,,,False
c8be435bb37880f219f7c0c124a6acf18df46e07,PMC,Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments,http://dx.doi.org/10.1371/journal.pone.0008326,PMC2790605,20016835,CC BY,"The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.",2009 Dec 16,"['Zhao, Huabin', 'Ru, Binghua', 'Teeling, Emma C.', 'Faulkes, Christopher G.', 'Zhang, Shuyi', 'Rossiter, Stephen J.']",PLoS One,,,False
cc49a6aeb47e524e172e40b0633745f66ac04f5b,PMC,Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments,http://dx.doi.org/10.1371/journal.pone.0008326,PMC2790605,20016835,CC BY,"The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.",2009 Dec 16,"['Zhao, Huabin', 'Ru, Binghua', 'Teeling, Emma C.', 'Faulkes, Christopher G.', 'Zhang, Shuyi', 'Rossiter, Stephen J.']",PLoS One,,,False
6e1ec9619b8e1f05cb76a414941e6eecb198ae07,PMC,Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments,http://dx.doi.org/10.1371/journal.pone.0008326,PMC2790605,20016835,CC BY,"The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.",2009 Dec 16,"['Zhao, Huabin', 'Ru, Binghua', 'Teeling, Emma C.', 'Faulkes, Christopher G.', 'Zhang, Shuyi', 'Rossiter, Stephen J.']",PLoS One,,,False
7bf733ca3c79a629454e7fb356e9510ddc219831,PMC,Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments,http://dx.doi.org/10.1371/journal.pone.0008326,PMC2790605,20016835,CC BY,"The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.",2009 Dec 16,"['Zhao, Huabin', 'Ru, Binghua', 'Teeling, Emma C.', 'Faulkes, Christopher G.', 'Zhang, Shuyi', 'Rossiter, Stephen J.']",PLoS One,,,False
d2595ff8328dfa3ea1479890056006db702b95c1,PMC,Rhodopsin Molecular Evolution in Mammals Inhabiting Low Light Environments,http://dx.doi.org/10.1371/journal.pone.0008326,PMC2790605,20016835,CC BY,"The ecological radiation of mammals to inhabit a variety of light environments is largely attributed to adaptive changes in their visual systems. Visual capabilities are conferred by anatomical features of the eyes as well as the combination and properties of their constituent light sensitive pigments. To test whether evolutionary switches to different niches characterized by dim-light conditions coincided with molecular adaptation of the rod pigment rhodopsin, we sequenced the rhodopsin gene in twenty-two mammals including several bats and subterranean mole-rats. We compared these to thirty-seven published mammal rhodopsin sequences, from species with divergent visual ecologies, including nocturnal, diurnal and aquatic groups. All taxa possessed an intact functional rhodopsin; however, phylogenetic tree reconstruction recovered a gene tree in which rodents were not monophyletic, and also in which echolocating bats formed a monophyletic group. These conflicts with the species tree appear to stem from accelerated evolution in these groups, both of which inhabit low light environments. Selection tests confirmed divergent selection pressures in the clades of subterranean rodents and bats, as well as in marine mammals that live in turbid conditions. We also found evidence of divergent selection pressures among groups of bats with different sensory modalities based on vision and echolocation. Sliding window analyses suggest most changes occur in transmembrane domains, particularly obvious within the pinnipeds; however, we found no obvious pattern between photopic niche and predicted spectral sensitivity based on known critical amino acids. This study indicates that the independent evolution of rhodopsin vision in ecologically specialised groups of mammals has involved molecular evolution at the sequence level, though such changes might not mediate spectral sensitivity directly.",2009 Dec 16,"['Zhao, Huabin', 'Ru, Binghua', 'Teeling, Emma C.', 'Faulkes, Christopher G.', 'Zhang, Shuyi', 'Rossiter, Stephen J.']",PLoS One,,,False
506b8507912862c6a87723c6a5babf2132748503,PMC,Expanding the Paradigms of Plant Pathogen Life History and Evolution of Parasitic Fitness beyond Agricultural Boundaries,http://dx.doi.org/10.1371/journal.ppat.1000693,PMC2790610,20041212,CC BY,,2009 Dec 24,"['Morris, Cindy E.', 'Bardin, Marc', 'Kinkel, Linda L.', 'Moury, Benoit', 'Nicot, Philippe C.', 'Sands, David C.']",PLoS Pathog,,,True
cf6c6fa2a4cf3fd624d4ef8291804a3fab3f1b2a,PMC,The SARS Coronavirus 3a Protein Causes Endoplasmic Reticulum Stress and Induces Ligand-Independent Downregulation of the Type 1 Interferon Receptor,http://dx.doi.org/10.1371/journal.pone.0008342,PMC2791231,20020050,CC BY,"The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is reported to cause apoptosis of infected cells and several of its proteins including the 3a accessory protein, are pro-apoptotic. Since the 3a protein localizes to the endoplasmic reticulum (ER)-Golgi compartment, its role in causing ER stress was investigated in transiently transfected cells. Cells expressing the 3a proteins showed ER stress based on activation of genes for the ER chaperones GRP78 and GRP94. Since ER stress can cause differential modulation of the unfolded protein response (UPR), which includes the inositol-requiring enzyme 1 (IRE-1), activating transcription factor 6 (ATF6) and PKR-like ER kinase (PERK) pathways, these were individually tested in 3a-expressing cells. Only the PERK pathway was found to be activated in 3a-expressing cells based on (1) increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) and inhibitory effects of a dominant-negative form of eIF2α on GRP78 promoter activity, (2) increased translation of activating transcription factor 4 (ATF4) mRNA, and (3) ATF4-dependent activation of the C/EBP homologous protein (CHOP) gene promoter. Activation of PERK affects innate immunity by suppression of type 1 interferon (IFN) signaling. The 3a protein was found to induce serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1) degradation motif and to increase IFNAR1 ubiquitination. Confocal microscopic analysis showed increased translocation of IFNAR1 into the lysosomal compartment and flow cytometry showed reduced levels of IFNAR1 in 3a-expressing cells. These results provide further mechanistic details of the pro-apoptotic effects of the SARS-CoV 3a protein, and suggest a potential role for it in attenuating interferon responses and innate immunity.",2009 Dec 17,"['Minakshi, Rinki', 'Padhan, Kartika', 'Rani, Manjusha', 'Khan, Nabab', 'Ahmad, Faizan', 'Jameel, Shahid']",PLoS One,,,True
557a14f4857aab6fa0b5d3b980aa241b113977ba,PMC,Breaking the Waves: Modelling the Potential Impact of Public Health Measures to Defer the Epidemic Peak of Novel Influenza A/H1N1,http://dx.doi.org/10.1371/journal.pone.0008356,PMC2791869,20027293,CC BY,"BACKGROUND: On June 11, 2009, the World Health Organization declared phase 6 of the novel influenza A/H1N1 pandemic. Although by the end of September 2009, the novel virus had been reported from all continents, the impact in most countries of the northern hemisphere has been limited. The return of the virus in a second wave would encounter populations that are still nonimmune and not vaccinated yet. We modelled the effect of control strategies to reduce the spread with the goal to defer the epidemic wave in a country where it is detected in a very early stage. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a deterministic SEIR model using the age distribution and size of the population of Germany based on the observed number of imported cases and the early findings for the epidemiologic characteristics described by Fraser (Science, 2009). We propose a two-step control strategy with an initial effort to trace, quarantine, and selectively give prophylactic treatment to contacts of the first 100 to 500 cases. In the second step, the same measures are focused on the households of the next 5,000 to 10,000 cases. As a result, the peak of the epidemic could be delayed up to 7.6 weeks if up to 30% of cases are detected. However, the cumulative attack rates would not change. Necessary doses of antivirals would be less than the number of treatment courses for 0.1% of the population. In a sensitivity analysis, both case detection rate and the variation of R0 have major effects on the resulting delay. CONCLUSIONS/SIGNIFICANCE: Control strategies that reduce the spread of the disease during the early phase of a pandemic wave may lead to a substantial delay of the epidemic. Since prophylactic treatment is only offered to the contacts of the first 10,000 cases, the amount of antivirals needed is still very limited.",2009 Dec 21,"['an der Heiden, Matthias', 'Buchholz, Udo', 'Krause, Gérard', 'Kirchner, Göran', 'Claus, Hermann', 'Haas, Walter H.']",PLoS One,,,True
7045ec55df870b7d611154081ae7e469883f64c4,PMC,Aurintricarboxylic Acid Is a Potent Inhibitor of Influenza A and B Virus Neuraminidases,http://dx.doi.org/10.1371/journal.pone.0008350,PMC2792043,20020057,CC BY,"BACKGROUND: Influenza viruses cause serious infections that can be prevented or treated using vaccines or antiviral agents, respectively. While vaccines are effective, they have a number of limitations, and influenza strains resistant to currently available anti-influenza drugs are increasingly isolated. This necessitates the exploration of novel anti-influenza therapies. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the potential of aurintricarboxylic acid (ATA), a potent inhibitor of nucleic acid processing enzymes, to protect Madin-Darby canine kidney cells from influenza infection. We found, by neutral red assay, that ATA was protective, and by RT-PCR and ELISA, respectively, confirmed that ATA reduced viral replication and release. Furthermore, while pre-treating cells with ATA failed to inhibit viral replication, pre-incubation of virus with ATA effectively reduced viral titers, suggesting that ATA may elicit its inhibitory effects by directly interacting with the virus. Electron microscopy revealed that ATA induced viral aggregation at the cell surface, prompting us to determine if ATA could inhibit neuraminidase. ATA was found to compromise the activities of virus-derived and recombinant neuraminidase. Moreover, an oseltamivir-resistant H1N1 strain with H274Y was also found to be sensitive to ATA. Finally, we observed additive protective value when infected cells were simultaneously treated with ATA and amantadine hydrochloride, an anti-influenza drug that inhibits M2-ion channels of influenza A virus. CONCLUSIONS/SIGNIFICANCE: Collectively, these data suggest that ATA is a potent anti-influenza agent by directly inhibiting the neuraminidase and could be a more effective antiviral compound when used in combination with amantadine hydrochloride.",2009 Dec 17,"['Hashem, Anwar M.', 'Flaman, Anathea S.', 'Farnsworth, Aaron', 'Brown, Earl G.', 'Van Domselaar, Gary', 'He, Runtao', 'Li, Xuguang']",PLoS One,,,True
0ced1f946cce007aa319a0ba38aef2c4b14dab0e,PMC,Identification of a novel conserved HLA-A*0201-restricted epitope from the spike protein of SARS-CoV,http://dx.doi.org/10.1186/1471-2172-10-61,PMC2792222,19958537,CC BY,"BACKGROUND: The spike (S) protein is a major structural glycoprotein of coronavirus (CoV), the causal agent of severe acute respiratory syndrome (SARS). The S protein is a potent target for SARS-specific cell-mediated immune responses. However, the mechanism CoV pathogenesis in SARS and the role of special CTLs in virus clearance are still largely uncharacterized. Here, we describe a study that leads to the identification of a novel HLA-A*0201-restricted epitope from conserved regions of S protein. RESULTS: First, different SARS-CoV sequences were analyzed to predict eight candidate peptides from conserved regions of the S protein based upon HLA-A*0201 binding and proteosomal cleavage. Four of eight candidate peptides were tested by HLA-A*0201 binding assays. Among the four candidate peptides, Sp8 (S(958-966), VLNDILSRL) induced specific CTLs both ex vivo in PBLs of healthy HLA-A2(+ )donors and in HLA-A2.1/K(b )transgenic mice immunized with a plasmid encoding full-length S protein. The immunized mice released IFN-γ and lysed target cells upon stimulation with Sp8 peptide-pulsed autologous dendritic cells in comparison to other candidates. CONCLUSION: These results suggest that Sp8 is a naturally processed epitope. We propose that Sp8 epitope should help in the characterization of mechanisms of virus control and immunopathology in SARS-CoV infection.",2009 Dec 3,"['Lv, Yanbo', 'Ruan, Zhihua', 'Wang, Li', 'Ni, Bing', 'Wu, Yuzhang']",BMC Immunol,,,True
98c1b2325128b3573b2793ba5d77dc07329c0195,PMC,Expression of the VP2 Protein of Murine Norovirus by a Translation Termination-Reinitiation Strategy,http://dx.doi.org/10.1371/journal.pone.0008390,PMC2793014,20027307,CC BY,"BACKGROUND: Expression of the minor virion structural protein VP2 of the calicivirus murine norovirus (MNV) is believed to occur by the unusual mechanism of termination codon-dependent reinitiation of translation. In this process, following translation of an upstream open reading frame (ORF) and termination at the stop codon, a proportion of 40S subunits remain associated with the mRNA and reinitiate at the AUG of a downstream ORF, which is typically in close proximity. Consistent with this, the VP2 start codon (AUG) of MNV overlaps the stop codon of the upstream VP1 ORF (UAA) in the pentanucleotide UAA UG. PRINCIPAL FINDINGS: Here, we confirm that MNV VP2 expression is regulated by termination-reinitiation and define the mRNA sequence requirements. Efficient reintiation is dependent upon 43 nt of RNA immediately upstream of the UAA UG site. Chemical and enzymatic probing revealed that the RNA in this region is not highly structured and includes an essential stretch of bases complementary to 18S rRNA helix 26 (Motif 1). The relative position of Motif 1 with respect to the UAA UG site impacts upon the efficiency of the process. Termination-reinitiation in MNV was also found to be relatively insensitive to the initiation inhibitor edeine. CONCLUSIONS: The termination-reinitiation signal of MNV most closely resembles that of influenza BM2. Similar to other viruses that use this strategy, base-pairing between mRNA and rRNA is likely to play a role in tethering the 40S subunit to the mRNA following termination at the VP1 stop codon. Our data also indicate that accurate recognition of the VP2 ORF AUG is not a pre-requisite for efficient reinitiation of translation in this system.",2009 Dec 22,"['Napthine, Sawsan', 'Lever, Robert A.', 'Powell, Michael L.', 'Jackson, Richard J.', 'Brown, T. David K.', 'Brierley, Ian']",PLoS One,,,True
99560951f295587952ccb543ccc8c214e6df62ae,PMC,"Genetics, Recombination and Clinical Features of Human Rhinovirus Species C (HRV-C) Infections; Interactions of HRV-C with Other Respiratory Viruses",http://dx.doi.org/10.1371/journal.pone.0008518,PMC2794544,20041158,CC0,"To estimate the frequency, molecular epidemiological and clinical associations of infection with the newly described species C variants of human rhinoviruses (HRV), 3243 diagnostic respiratory samples referred for diagnostic testing in Edinburgh were screened using a VP4-encoding region-based selective polymerase chain reaction (PCR) for HRV-C along with parallel PCR testing for 13 other respiratory viruses. HRV-C was the third most frequently detected behind respiratory syncytial virus (RSV) and adenovirus, with 141 infection episodes detected among 1885 subjects over 13 months (7.5%). Infections predominantly targeted the very young (median age 6–12 months; 80% of infections in those <2 years), occurred throughout the year but with peak incidence in early winter months. HRV-C was detected significantly more frequently among subjects with lower (LRT) and upper respiratory tract (URT) disease than controls without respiratory symptoms; HRV-C mono-infections were the second most frequently detected virus (behind RSV) in both disease presentations (6.9% and 7.8% of all cases respectively). HRV variants were classified by VP4/VP2 sequencing into 39 genotypically defined types, increasing the current total worldwide to 60. Through sequence comparisons of the 5′untranslated region (5′UTR), the majority grouped with species A (n = 96; 68%, described as HRV-Ca), the remainder forming a phylogenetically distinct 5′UTR group (HRV-Cc). Multiple and bidirectional recombination events between HRV-Ca and HRV-Cc variants and with HRV species A represents the most parsimonious explanation for their interspersed phylogeny relationships in the VP4/VP2-encoding region. No difference in age distribution, seasonality or disease associations was identified between HRV-Ca and HRV-Cc variants. HRV-C-infected subjects showed markedly reduced detection frequencies of RSV and other respiratory viruses, providing evidence for a major interfering effect of HRV-C on susceptibility to other respiratory virus infections. HRV-C's disease associations, its prevalence and evidence for interfering effects on other respiratory viruses mandates incorporation of rhinoviruses into future diagnostic virology screening.",2009 Dec 30,"['Wisdom, Anne', 'Kutkowska, Aldona E.', 'McWilliam Leitch, E. Carol', 'Gaunt, Eleanor', 'Templeton, Kate', 'Harvala, Heli', 'Simmonds, Peter']",PLoS One,,,True
73eb67835207270107c1e76b4675a92b3b58a575,PMC,Streptococcus pneumoniae Coinfection Is Correlated with the Severity of H1N1 Pandemic Influenza,http://dx.doi.org/10.1371/journal.pone.0008540,PMC2795195,20046873,CC BY,"BACKGROUND: Initial reports in May 2009 of the novel influenza strain H1N1pdm estimated a case fatality rate (CFR) of 0.6%, similar to that of seasonal influenza. In July 2009, however, Argentina reported 3056 cases with 137 deaths, representing a CFR of 4.5%. Potential explanations for increased CFR included virus reassortment or genetic drift, or infection of a more vulnerable population. Virus genomic sequencing of 26 Argentinian samples representing both severe and mild disease indicated no evidence of reassortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence. Furthermore, no evidence was found for increased frequency of risk factors for H1N1pdm disease. METHODS/PRINCIPAL FINDINGS: We examined nasopharyngeal swab samples (NPS) from 199 cases of H1N1pdm infection from Argentina with MassTag PCR, testing for 33 additional microbial agents. The study population consisted of 199 H1N1pdm-infected subjects sampled between 23 June and 4 July 2009. Thirty-nine had severe disease defined as death (n = 20) or hospitalization (n = 19); 160 had mild disease. At least one additional agent of potential pathogenic importance was identified in 152 samples (76%), including Streptococcus pneumoniae (n = 62); Haemophilus influenzae (n = 104); human respiratory syncytial virus A (n = 11) and B (n = 1); human rhinovirus A (n = 1) and B (n = 4); human coronaviruses 229E (n = 1) and OC43 (n = 2); Klebsiella pneumoniae (n = 2); Acinetobacter baumannii (n = 2); Serratia marcescens (n = 1); and Staphylococcus aureus (n = 35) and methicillin-resistant S. aureus (MRSA, n = 6). The presence of S. pneumoniae was strongly correlated with severe disease. S. pneumoniae was present in 56.4% of severe cases versus 25% of mild cases; more than one-third of H1N1pdm NPS with S. pneumoniae were from subjects with severe disease (22 of 62 S. pneumoniae-positive NPS, p = 0.0004). In subjects 6 to 55 years of age, the adjusted odds ratio (OR) of severe disease in the presence of S. pneumoniae was 125.5 (95% confidence interval [CI], 16.95, 928.72; p<0.0001). CONCLUSIONS/SIGNIFICANCE: The association of S. pneumoniae with morbidity and mortality is established in the current and previous influenza pandemics. However, this study is the first to demonstrate the prognostic significance of non-invasive antemortem diagnosis of S. pneumoniae infection and may provide insights into clinical management.",2009 Dec 31,"['Palacios, Gustavo', 'Hornig, Mady', 'Cisterna, Daniel', 'Savji, Nazir', 'Bussetti, Ana Valeria', 'Kapoor, Vishal', 'Hui, Jeffrey', 'Tokarz, Rafal', 'Briese, Thomas', 'Baumeister, Elsa', 'Lipkin, W. Ian']",PLoS One,,,True
1b62107420aac57e1b7e2d496183036dec1ab905,PMC,Outdoor environments and human pathogens in air,http://dx.doi.org/10.1186/1476-069X-8-S1-S15,PMC2796493,20102582,CC BY,"Are pathogens in outdoor air a health issue at present or will they become a problem in the future? A working group called AirPath - Outdoor Environments and Human Pathogens in Air was set up in 2007 at University College London, UK with the aim of opening new discussion and creating a research network to investigate the science and impacts of outdoor pathogens. Our objective in this paper is to review and discuss the following areas: What is the source of human pathogens in outdoor air? What current, developing and future techniques do we need? Can we identify at-risk groups in relation to their activities and environments? How do we prepare for the anticipated challenges of environmental change and new and emerging diseases? And how can we control for and prevent pathogens in outdoor environments? We think that this work can benefit the wider research community and policy makers by providing a concise overview of various research aspects and considerations which may be important to their work.",2009 Dec 21,"['Lai, Ka man', 'Emberlin, Jean', 'Colbeck, Ian']",Environ Health,,,True
3a324b07dddba6a95b23d5cf90c4f0756b87afe4,PMC,"Let the sun shine in: effects of ultraviolet radiation on invasive pneumococcal disease risk in Philadelphia, Pennsylvania",http://dx.doi.org/10.1186/1471-2334-9-196,PMC2797517,19961583,CC BY,"BACKGROUND: Streptococcus pneumoniae is a common cause of community acquired pneumonia and bacteremia. Excess wintertime mortality related to pneumonia has been noted for over a century, but the seasonality of invasive pneumococcal disease (IPD) has been described relatively recently and is poorly understood. Improved understanding of environmental influence on disease seasonality has taken on new urgency due to global climate change. METHODS: We evaluated 602 cases of IPD reported in Philadelphia County, Pennsylvania, from 2002 to 2007. Poisson regression models incorporating seasonal smoothers were used to identify associations between weekly weather patterns and case counts. Associations between acute (day-to-day) environmental fluctuations and IPD occurrence were evaluated using a case-crossover approach. Effect modification across age and sex strata was explored, and meta-regression models were created using stratum-specific estimates for effect. RESULTS: IPD incidence was greatest in the wintertime, and spectral decomposition revealed a peak at 51.0 weeks, consistent with annual periodicity. After adjustment for seasonality, yearly increases in reporting, and temperature, weekly incidence was found to be associated with clear-sky UV index (IRR per unit increase in index: 0.70 [95% CI 0.54-0.91]). The effect of UV index was highest among young strata and decreased with age. At shorter time scales, only an association with increases in ambient sulphur oxides was linked to disease risk (OR for highest tertile of exposure 0.75, 95% CI 0.60 to 0.93). CONCLUSION: We confirmed the wintertime predominance of IPD in a major urban center. The major predictor of IPD in Philadelphia is extended periods of low UV radiation, which may explain observed wintertime seasonality. The mechanism of action of diminished light exposure on disease occurrence may be due to direct effects on pathogen survival or host immune function via altered 1,25-(OH)(2)-vitamin-D metabolism. These findings may suggest less diminution in future IPD risk with climate change than would be expected if wintertime seasonality was driven by temperature.",2009 Dec 4,"['White, Alexander NJ', 'Ng, Victoria', 'Spain, C Victor', 'Johnson, Caroline C', 'Kinlin, Laura M', 'Fisman, David N']",BMC Infect Dis,,,True
408c98fbba5d5584cc7fda96ec9b307d1cbd73bc,PMC,Recombinant porcine rotavirus VP4 and VP4-LTB expressed in Lactobacillus casei induced mucosal and systemic antibody responses in mice,http://dx.doi.org/10.1186/1471-2180-9-249,PMC2797526,19958557,CC BY,BACKGROUND: Porcine rotavirus infection is a significant cause of morbidity and mortality in the swine industry necessitating the development of effective vaccines for the prevention of infection. Immune responses associated with protection are primarily mucosal in nature and induction of mucosal immunity is important for preventing porcine rotavirus infection. RESULTS: Lactobacillus casei expressing the major protective antigen VP4 of porcine rotavirus (pPG612.1-VP4) or VP4-LTB (heat-labile toxin B subunit from Echerichia coli) (pPG612.1-VP4-LTB) fusion protein was used to immunize mice orally. The expression of recombinant pPG612.1-VP4 and pPG612.1-VP4-LTB was confirmed by SDS-PAGE and Western blot analysis and surface-displayed expression on L. casei was verified by immunofluorescence. Mice orally immunized with recombinant protein-expressing L. casei produced high levels of serum immunoglobulin G (IgG) and mucosal IgA. The IgA titters from mice immunized with pPG612.1-VP4-LTB were higher than titters from pPG612.1-VP4-immunized mice. The induced antibodies demonstrated neutralizing effects on RV infection. CONCLUSION: These results demonstrated that VP4 administered in the context of an L. casei expression system is an effective method for stimulating mucosal immunity and that LTB served to further stimulate mucosal immunity suggesting that this strategy can be adapted for use in pigs.,2009 Dec 4,"['Qiao, Xinyuan', 'Li, Guiwei', 'Wang, Xiangqing', 'Li, Xiaojing', 'Liu, Min', 'Li, Yijing']",BMC Microbiol,,,True
89dc30e7b46b476142978f461feb4ecca1bf89b7,PMC,Listeriolysin O Is Necessary and Sufficient to Induce Autophagy during Listeria monocytogenes Infection,http://dx.doi.org/10.1371/journal.pone.0008610,PMC2797616,20062534,CC BY,"BACKGROUND: Recent studies have suggested that autophagy is utilized by cells as a protective mechanism against Listeria monocytogenes infection. METHODOLOGY/PRINCIPAL FINDINGS: However we find autophagy has no measurable role in vacuolar escape and intracellular growth in primary cultured bone marrow derived macrophages (BMDMs) deficient for autophagy (atg5(−/−)). Nevertheless, we provide evidence that the pore forming activity of the cholesterol-dependent cytolysin listeriolysin O (LLO) can induce autophagy subsequent to infection by L. monocytogenes. Infection of BMDMs with L. monocytogenes induced microtubule-associated protein light chain 3 (LC3) lipidation, consistent with autophagy activation, whereas a mutant lacking LLO did not. Infection of BMDMs that express LC3-GFP demonstrated that wild-type L. monocytogenes was encapsulated by LC3-GFP, consistent with autophagy activation, whereas a mutant lacking LLO was not. Bacillus subtilis expressing either LLO or a related cytolysin, perfringolysin O (PFO), induced LC3 colocalization and LC3 lipidation. Further, LLO-containing liposomes also recruited LC3-GFP, indicating that LLO was sufficient to induce targeted autophagy in the absence of infection. The role of autophagy had variable effects depending on the cell type assayed. In atg5(−/−) mouse embryonic fibroblasts, L. monocytogenes had a primary vacuole escape defect. However, the bacteria escaped and grew normally in atg5(−/−) BMDMs. CONCLUSIONS/SIGNIFICANCE: We propose that membrane damage, such as that caused by LLO, triggers bacterial-targeted autophagy, although autophagy does not affect the fate of wild-type intracellular L. monocytogenes in primary BMDMs.",2010 Jan 6,"['Meyer-Morse, Nicole', 'Robbins, Jennifer R.', 'Rae, Chris S.', 'Mochegova, Sofia N.', 'Swanson, Michele S.', 'Zhao, Zijiang', 'Virgin, Herbert W.', 'Portnoy, Daniel']",PLoS One,,,True
5ab2ff8df3b1bc8a71ab66025f5dcee729242583,PMC,Intracranial Administration of P Gene siRNA Protects Mice from Lethal Chandipura Virus Encephalitis,http://dx.doi.org/10.1371/journal.pone.0008615,PMC2797643,20062542,CC BY,"BACKGROUND: In parts of India, Chandipura Virus (CHPV) has emerged as an encephalitis causing pathogen in both epidemic and sporadic forms. This pediatric disease follows rapid course leading to 55–75% mortality. In the absence of specific treatment, effectiveness of RNA interference (RNAi) was evaluated. METHODS AND FINDINGS: Efficacy of synthetic short interfering RNA (siRNA) or short hairpin RNA (shRNA) in protecting mice from CHPV infection was assessed. The target genes were P and M genes primarily because important role of the former in viral replication and lethal nature of the latter. Real time one step RT-PCR and plaque assay were used for the assessment of gene silencing. Using pAcGFP1N1-CHPV-P, we showed that P-2 siRNA was most efficient in reducing the expression of P gene in-vitro. Both quantitative assays documented 2logs reduction in the virus titer when P-2, M-5 or M-6 siRNAs were transfected 2hr post infection (PI). Use of these siRNAs in combination did not result in enhanced efficiency. P-2 siRNA was found to tolerate four mismatches in the center. As compared to five different shRNAs, P-2 siRNA was most effective in inhibiting CHPV replication. An extended survival was noted when mice infected intracranially with 100 LD(50) CHPV were treated with cationic lipid complexed 5 µg P-2 siRNA simultaneously. Infection with 10LD(50) and treatment with two doses of siRNA first, simultaneously and second 24 hr PI, resulted in 70% survival. Surviving mice showed 4logs less CHPV titers in brain without histopathological changes or antibody response. Gene expression profiles of P-2 siRNA treated mice showed no interferon response. First dose of siRNA at 2hr or 4hr PI with second dose at 24hr resulted in 40% and 20% survival respectively suggesting potential application in therapy. CONCLUSIONS: The results highlight therapeutic potential of siRNA in treating rapid and fatal Chandipura encephalitis.",2010 Jan 7,"['Kumar, Satyendra', 'Arankalle, Vidya A.']",PLoS One,,,True
d55f09671ad483ed5c25dbff97c970e08c6be947,PMC,The neck-region polymorphism of DC-SIGNR in peri-centenarian from Han Chinese Population,http://dx.doi.org/10.1186/1471-2350-10-134,PMC2797785,20003397,CC BY,"BACKGROUND: DC-SIGNR (also called CD209L) has been extensively studied on its role in host genetic predisposition to viral infection. In particular, variable number tandem repeat (VNTR) of the neck-region of DC-SIGNR is highly polymorphic and the polymorphism has been investigated for genetic predisposition to various infectious diseases, though conflicting results had been reported. As infection is a major cause of human death and a mechanism of natural selection, we hypothesized that VNTR polymorphism of DC-SIGNR might have an effect on human life span. METHODS: Here we collected 361 peri-centenarian individuals (age ≥94 for female and age ≥90 for male) and 342 geographically matched controls (age 22-53, mean 35.0 ± 12.0) from Han Chinese. The VNTR polymorphism of the neck region was determined by PCR and genotype was called by separating the PCR products in agarose gel. RESULTS: A total of 11 genotypes and 5 alleles were found in our population. The genotype distribution, allele frequencies and homozygote proportion did not show a significant difference between peri-centenarian and control group. As gender differences in lifespan are ubiquitously observed throughout the animal kingdom, we then stratified the samples by gender. There was more 6/7 genotypes in female peri-centenarian group than that in female control group, at a marginal level of significance (5.56 vs. 1.28%, p = 0.041). The difference was not significant after correction by Bonferroni method. It suggests a possible differential effect of DC-SIGNR VNTR genotypes between sexes. Further studies are warranted to confirm our preliminary findings and investigate the mechanisms of the underlying functions. CONCLUSIONS: Our study indicated that there was absence of association between the neck region polymorphism of DC-SIGNR and longevity in Han Chinese population. But the question of whether the DC-SIGNR could affect longevity in a gender-specific pattern remains open.",2009 Dec 14,"['Li, Hui', 'Wang, Cheng-Ye', 'Wang, Jia-Xin', 'Tang, Nelson Leung-Sang', 'Xie, Liang', 'Gong, Yuan-Ying', 'Yang, Zhao', 'Xu, Liang-You', 'Kong, Qing-Peng', 'Zhang, Ya-Ping']",BMC Med Genet,,,True
55cc676ae1d05bf9cacceacd765846abfeae92a9,PMC,Translational Studies of Alcoholism: Bridging the Gap,,PMC2798743,20041042,CC0,"Human studies are necessary to identify and classify the brain systems predisposing individuals to develop alcohol use disorders and those modified by alcohol, while animal models of alcoholism are essential for a mechanistic understanding of how chronic voluntary alcohol consumption becomes compulsive, how brain systems become damaged, and how damage resolves. Our current knowledge of the neuroscience of alcohol dependence has evolved from the interchange of information gathered from both human alcoholics and animal models of alcoholism. Together, studies in humans and animal models have provided support for the involvement of specific brain structures over the course of alcohol addiction, including the prefrontal cortex, basal ganglia, cerebellum, amygdala, hippocampus, and the hypothalamic–pituitary–adrenal axis.",2008,"['Zahr, Natalie M.', 'Sullivan, Edith V.']",Alcohol Res Health,,,True
73af6e73949ec28b7c3b13d24a9168e891d7bb23,PMC,Developing 21(st )century accreditation standards for teaching hospitals: the Taiwan experience,http://dx.doi.org/10.1186/1472-6963-9-232,PMC2801490,20003505,CC BY,"BACKGROUND: The purpose of this study is to establish teaching hospital accreditation standards anew with the hope that Taiwan's teaching hospitals can live up to the expectations of our society and ensure quality teaching. METHODS: The development process lasted two years, 2005-2006, and was separated into three stages. The first stage centered on leadership meetings and consensus building, the second on drafting the new standards with expert focus groups, and the third on a pilot study and subsequent revision. RESULTS: Our new teaching hospital accreditation standards have six categories and 95 standards as follows: educational resources (20 items), teaching and training plans and outcomes (42 items), research and results (9 items), development of clinical faculty and continuing education (8 items), academic exchanges and community education (8 items), and administration (8 items). CONCLUSIONS: The new standards have proven feasible and posed reasonable challenges in the pilot study. We hope the new standards will strengthen teaching and research, and improve the quality of hospital services at the same time.",2009 Dec 15,"['Huang, Chung-I', 'Wung, Cathy', 'Yang, Che-Ming']",BMC Health Serv Res,,,True
0f3fae76f66b8f351abbef071fdf7e6efc1c325c,PMC,Development of a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) system for a highly sensitive detection of enterovirus in the stool samples of acute flaccid paralysis cases,http://dx.doi.org/10.1186/1471-2334-9-208,PMC2803793,20015403,CC BY,"BACKGROUND: In the global eradication program for poliomyelitis, the laboratory diagnosis plays a critical role by isolating poliovirus (PV) from the stool samples of acute flaccid paralysis (AFP) cases. In this study, we developed a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) system for a rapid and highly sensitive detection of enterovirus including PV to identify stool samples positive for enterovirus including PV. METHODS: A primer set was designed for RT-LAMP to detect enterovirus preferably those with PV-like 5'NTRs of the viral genome. The sensitivity of RT-LAMP system was evaluated with prototype strains of enterovirus. Detection of enterovirus from stool extracts was examined by using RT-LAMP system. RESULTS: We detected at least 400 copies of the viral genomes of PV(Sabin) strains within 90 min by RT-LAMP with the primer set. This RT-LAMP system showed a preference for Human enterovirus species C (HEV-C) strains including PV, but exhibited less sensitivity to the prototype strains of HEV-A and HEV-B (detection limits of 7,400 to 28,000 copies). Stool extracts, from which PV, HEV-C, or HEV-A was isolated in the cell culture system, were mostly positive by RT-LAMP method (positive rates of 15/16 (= 94%), 13/14 (= 93%), and 4/4 (= 100%), respectively). The positive rate of this RT-LAMP system for stool extracts from which HEV-B was isolated was lower than that of HEV-C (positive rate of 11/21 (= 52%)). In the stool samples, which were negative for enterovirus isolation by the cell culture system, we found that two samples were positive for RT-LAMP (positive rates of 2/38 (= 5.3%)). In these samples, enterovirus 96 was identified by sequence analysis utilizing a seminested PCR system. CONCLUSIONS: RT-LAMP system developed in this study showed a high sensitivity comparable to that of the cell culture system for the detection of PV, HEV-A, and HEV-C, but less sensitivity to HEV-B. This RT-LAMP system would be useful for the direct detection of enterovirus from the stool extracts.",2009 Dec 16,"['Arita, Minetaro', 'Ling, Hua', 'Yan, Dongmei', 'Nishimura, Yorihiro', 'Yoshida, Hiromu', 'Wakita, Takaji', 'Shimizu, Hiroyuki']",BMC Infect Dis,,,True
53003a256222203353a3aec2be3ada210544775f,PMC,Diagnosis of Parasitic Diseases: Old and New Approaches,http://dx.doi.org/10.1155/2009/278246,PMC2804041,20069111,CC BY,"Methods for the diagnosis of infectious diseases have stagnated in the last 20–30 years. Few major advances in clinical diagnostic testing have been made since the introduction of PCR, although new technologies are being investigated. Many tests that form the backbone of the “modern” microbiology laboratory are based on very old and labour-intensive technologies such as microscopy for malaria. Pressing needs include more rapid tests without sacrificing sensitivity, value-added tests, and point-of-care tests for both high- and low-resource settings. In recent years, research has been focused on alternative methods to improve the diagnosis of parasitic diseases. These include immunoassays, molecular-based approaches, and proteomics using mass spectrometry platforms technology. This review summarizes the progress in new approaches in parasite diagnosis and discusses some of the merits and disadvantages of these tests.",2009 Dec 30,"Ndao, Momar",Interdiscip Perspect Infect Dis,,,True
5e8669392733113d4bbaeebd9347764807872fa2,PMC,Prophylactic and therapeutic activity of fully human monoclonal antibodies directed against Influenza A M2 protein,http://dx.doi.org/10.1186/1743-422X-6-224,PMC2804611,20025741,CC BY,"Influenza virus infection is a prevalent disease in humans. Antibodies against hemagglutinin have been shown to prevent infection and hence hemagglutinin is the major constituent of current vaccines. Antibodies directed against the highly conserved extracellular domain of M2 have also been shown to mediate protection against Influenza A infection in various animal models. Active vaccination is generally considered the best approach to combat viral diseases. However, passive immunization is an attractive alternative, particularly in acutely exposed or immune compromized individuals, young children and the elderly. We recently described a novel method for the rapid isolation of natural human antibodies by mammalian cell display. Here we used this approach to isolate human monoclonal antibodies directed against the highly conserved extracellular domain of the Influenza A M2 protein. The identified antibodies bound M2 peptide with high affinities, recognized native cell-surface expressed M2 and protected mice from a lethal influenza virus challenge. Moreover, therapeutic treatment up to 2 days after infection was effective, suggesting that M2-specific monoclonals have a great potential as immunotherapeutic agents against Influenza infection.",2009 Dec 21,"['Beerli, Roger R', 'Bauer, Monika', 'Schmitz, Nicole', 'Buser, Regula B', 'Gwerder, Myriam', 'Muntwiler, Simone', 'Renner, Wolfgang A', 'Saudan, Philippe', 'Bachmann, Martin F']",Virol J,,,True
c6e819e9d3fdfd19cafd2ddf160b9ed2cfd9a27a,PMC,Public perceptions of quarantine: community-based telephone survey following an infectious disease outbreak,http://dx.doi.org/10.1186/1471-2458-9-470,PMC2804616,20015400,CC BY,"BACKGROUND: The use of restrictive measures such as quarantine draws into sharp relief the dynamic interplay between the individual rights of the citizen on the one hand and the collective rights of the community on the other. Concerns regarding infectious disease outbreaks (SARS, pandemic influenza) have intensified the need to understand public perceptions of quarantine and other social distancing measures. METHODS: We conducted a telephone survey of the general population in the Greater Toronto Area in Ontario, Canada. Computer-assisted telephone interviewing (CATI) technology was used. A final sample of 500 individuals was achieved through standard random-digit dialing. RESULTS: Our data indicate strong public support for the use of quarantine when required and for serious legal sanctions against those who fail to comply. This support is contingent both on the implementation of legal safeguards to protect against inappropriate use and on the provision of psychosocial supports for those affected. CONCLUSION: To engender strong public support for quarantine and other restrictive measures, government officials and public health policy-makers would do well to implement a comprehensive system of supports and safeguards, to educate and inform frontline public health workers, and to engage the public at large in an open dialogue on the ethical use of restrictive measures during infectious disease outbreaks.",2009 Dec 16,"['Tracy, C Shawn', 'Rea, Elizabeth', 'Upshur, Ross EG']",BMC Public Health,,,True
f6ed1f1e9999e57793addb1c9c54f61c7861a995,PMC,A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1,http://dx.doi.org/10.1186/1471-2172-10-64,PMC2804704,20017901,CC BY,"BACKGROUND: Mycobacterium tuberculosis (MTB) is a major cause of morbidity and mortality in the world. To combat against this pathogen, immune cells release cytokines including tumor necrosis factor-α (TNF-α), which is pivotal in the development of protective granulomas. Our previous results showed that Bacillus Calmette Guerin (BCG), a mycobacterium used as a model to investigate the immune response against MTB, stimulates the induction of TNF-α via mitogen-activated protein kinase (MAPK) in human blood monocytes. Since MAPK phosphatase-1 (MKP-1) is known to regulate MAPK activities, we examined whether MKP-1 plays a role in BCG-induced MAPK activation and cytokine expression. RESULTS: Primary human blood monocytes were treated with BCG and assayed for MKP-1 expression. Our results demonstrated that following exposure to BCG, there was an increase in the expression of MKP-1. Additionally, the induction of MKP-1 was regulated by p38 MAPK and extracellular signal-regulated kinase 1 and 2 (ERK1/2). Surprisingly, when MKP-1 expression was blocked by its specific siRNA, there was a significant decrease in the levels of phospho-MAPK (p38 MAPK and ERK1/2) and TNF-α inducible by BCG. CONCLUSIONS: Since TNF-α is pivotal in granuloma formation, the results indicated an unexpected positive function of MKP-1 against mycobacterial infection as opposed to its usual phosphatase activity.",2009 Dec 17,"['Cheung, Benny KW', 'Yim, Howard CH', 'Lee, Norris CM', 'Lau, Allan SY']",BMC Immunol,,,True
331d9c08ce93e1ca8843610514f7ecb1d83dd883,PMC,Mutagenesis of the transmembrane domain of the SARS coronavirus spike glycoprotein: refinement of the requirements for SARS coronavirus cell entry,http://dx.doi.org/10.1186/1743-422X-6-230,PMC2805634,20034394,CC BY,"BACKGROUND: The spike protein (S) of SARS Coronavirus (SARS-CoV) mediates entry of the virus into target cells, including receptor binding and membrane fusion. Close to or in the viral membrane, the S protein contains three distinct motifs: a juxtamembrane aromatic part, a central highly hydrophobic stretch and a cysteine rich motif. Here, we investigate the role of aromatic and hydrophobic parts of S in the entry of SARS CoV and in cell-cell fusion. This was investigated using the previously described SARS pseudotyped particles system (SARSpp) and by fluorescence-based cell-cell fusion assays. RESULTS: Mutagenesis showed that the aromatic domain was crucial for SARSpp entry into cells, with a likely role in pore enlargement. Introduction of lysine residues in the hydrophobic stretch of S also resulted in a block of entry, suggesting the borders of the actual transmembrane domain. Surprisingly, replacement of a glycine residue, situated close to the aromatic domain, with a lysine residue was tolerated, whereas the introduction of a lysine adjacent to the glycine, was not. In a model, we propose that during fusion, the lateral flexibility of the transmembrane domain plays a critical role, as do the tryptophans and the cysteines. CONCLUSIONS: The aromatic domain plays a crucial role in the entry of SARS CoV into target cells. The positioning of the aromatic domain and the hydrophobic domain relative to each other is another essential characteristic of this membrane fusion process.",2009 Dec 24,"['Corver, Jeroen', 'Broer, Rene', 'van Kasteren, Puck', 'Spaan, Willy']",Virol J,,,True
ecf15cf19a780b1f9e58e9a5b35402ca5886adab,PMC,EBNA3C interacts with Gadd34 and counteracts the unfolded protein response,http://dx.doi.org/10.1186/1743-422X-6-231,PMC2805635,20040105,CC BY,"EBNA3C is an EBV-encoded nuclear protein, essential for proliferation of EBV infected B-lymphocytes. Using EBNA3C amino acids 365-545 in a yeast two hybrid screen, we found an interaction with the Growth Arrest and DNA-damage protein, Gadd34. When both proteins are overexpressed, Gadd34 can interact with EBNA3C in both nuclear and cytoplasmic compartments. Amino acids 483-610 of Gadd34, including the two PP1a interaction, and the HSV-1 ICPγ34.5 homology domains, are required for the interaction. Furthermore, interaction is lost with a mutant of EBNA3C ((509 )DVIEVID (515)→AVIAVIA), that abolishes EBNA3C coactivation ability as well as SUMO interaction[1]. In B-cells, Gadd34, and EBNA3C are present in a complex with PP1a using microcystin sepharose affinity purification, Using a lymphoblastoid cell line in which EBNA3C protein levels are conditional on hydroxytamoxifen, surprisingly, we found that (i) EBNA3C maintains phosphorylation of eIF2α at serine 51, and (ii) protects against ER stress induced activation of the unfolded protein response as measured by XBP1 (u) versus XBP1(s) protein expression and N-terminal ATF6 cleavage. In reporter assays, overexpression of Gadd34 enhances EBNA3C's ability to co-activate EBNA2 activation of the LMP1 promoter. Collectively the data suggest that EBNA3C interacts with Gadd34, activating the upstream component of the UPR (eIF2α phosphorylation) while preventing downstream UPR events (XBP1 activation and ATF6 cleavage).",2009 Dec 29,"['Garrido, Jose L', 'Maruo, Seijii', 'Takada, Kenzo', 'Rosendorff, Adam']",Virol J,,,True
b4e5ee4be574a65dee1c7fca178580f9db58087f,PMC,Global Expression Profiling in Epileptogenesis: Does It Add to the Confusion?,http://dx.doi.org/10.1111/j.1750-3639.2008.00254.x,PMC2805866,19243383,CC BY,"Since the inception of global gene expression profiling platforms in the mid-1990s, there has been a significant increase in publications of differentially expressed genes in the process of epileptogenesis. In particular for mesial temporal lobe epilepsy, the presence of a latency period between the first manifestation of seizures to chronic epilepsy provides the opportunity for therapeutic interventions at the molecular biology level. Using global expression profiling techniques, approximately 2000 genes have been published demonstrating differential expression in mesial temporal epilepsy. The majority of these changes, however, are specific to laboratory or experimental conditions with only 53 genes demonstrating changes in more than two publications. To this end, we review the current status of gene expression profiling in epileptogenesis and suggest standard guidelines to be followed for greater accuracy and reproducibility of results.",2010 Jan,"['Wang, Yi Yuen', 'Smith, Paul', 'Murphy, Michael', 'Cook, Mark']",Brain Pathol,,,True
a8b801f23efa409e89226176fec4c0517e330717,PMC,Linking mechanistic and behavioral responses to sublethal esfenvalerate exposure in the endangered delta smelt; Hypomesus transpacificus (Fam. Osmeridae),http://dx.doi.org/10.1186/1471-2164-10-608,PMC2806348,20003521,CC BY,"BACKGROUND: The delta smelt (Hypomesus transpacificus) is a pelagic fish species listed as endangered under both the USA Federal and Californian State Endangered Species Acts and considered an indicator of ecosystem health in its habitat range, which is limited to the Sacramento-San Joaquin estuary in California, USA. Anthropogenic contaminants are one of multiple stressors affecting this system, and among them, current-use insecticides are of major concern. Interrogative tools are required to successfully monitor effects of contaminants on the delta smelt, and to research potential causes of population decline in this species. We have created a microarray to investigate genome-wide effects of potentially causative stressors, and applied this tool to assess effects of the pyrethroid insecticide esfenvalerate on larval delta smelt. Selected genes were further investigated as molecular biomarkers using quantitative PCR analyses. RESULTS: Exposure to esfenvalerate affected swimming behavior of larval delta smelt at concentrations as low as 0.0625 μg.L(-1), and significant differences in expression were measured in genes involved in neuromuscular activity. Alterations in the expression of genes associated with immune responses, along with apoptosis, redox, osmotic stress, detoxification, and growth and development appear to have been invoked by esfenvalerate exposure. Swimming impairment correlated significantly with expression of aspartoacylase (ASPA), an enzyme involved in brain cell function and associated with numerous human diseases. Selected genes were investigated for their use as molecular biomarkers, and strong links were determined between measured downregulation in ASPA and observed behavioral responses in fish exposed to environmentally relevant pyrethroid concentrations. CONCLUSIONS: The results of this study show that microarray technology is a useful approach in screening for, and generation of molecular biomarkers in endangered, non-model organisms, identifying specific genes that can be directly linked with sublethal toxicological endpoints; such as changes in expression levels of neuromuscular genes resulting in measurable swimming impairments. The developed microarrays were successfully applied on larval fish exposed to esfenvalerate, a known contaminant of the Sacramento-San Joaquin estuary, and has permitted the identification of specific biomarkers which could provide insight into the factors contributing to delta smelt population decline.",2009 Dec 15,"['Connon, Richard E', 'Geist, Juergen', 'Pfeiff, Janice', 'Loguinov, Alexander V', ""D'Abronzo, Leandro S"", 'Wintz, Henri', 'Vulpe, Christopher D', 'Werner, Inge']",BMC Genomics,,,True
87a937ec2cd698b7d24ade1803a22852747ec8c7,PMC,Efficacy and safety of 2-hour urokinase regime in acute pulmonary embolism: a randomized controlled trial,http://dx.doi.org/10.1186/1465-9921-10-128,PMC2806365,20040086,CC BY,"BACKGROUNDS: Urokinase (UK) 2 200 U/kg·h for 12 hours infusion(UK-12 h)is an ACCP recommended regimen in treating acute pulmonary embolism (PE). It is unclear whether this dose and time can be reduced further. We compared the efficacy and safety of 20, 000 U/kg for 2 hours (UK-2 h) with the UK-12 h regime in selected PE patients. METHODS: A randomized trial involving 129 patients was conducted. Patients with acute PE were randomly assigned to receive either UK-12 h (n = 70), or UK-2 h (n = 59). The efficacy was determined by the improvement of right heart dysfunction and perfusion defect at 24 h and 14 d post UK treatment. The bleeding incidence, death rate and PE recurrence were also evaluated. RESULTS: Similarly significant improvements in right heart dysfunction and lung perfusion defects were observed in both groups. Overall bleeding incidents were low in both groups. Major bleeding directly associated with UK infusion occurred in one patient in the UK-2 h group and one in the UK-12 h group. Mortality rates were low, with one reported fatal recurrent in the UK-12 h group and none in the UK-2 h group. When the rate of bleeding, death and PE recurrence were compared separately in the hemodynamic instability and the massive anatomic obstruction subgroups, no significant difference was found. CONCLUSIONS: The UK-2 h regimen exhibits similar efficacy and safety as the UK-12 h regimen for acute PE. TRIAL REGISTRATION: Clinical trial registered with http://clinicaltrials.gov/ct2/show/NCT00799968 (Identifier: NCT 00799968)",2009 Dec 29,"['Wang, Chen', 'Zhai, Zhenguo', 'Yang, Yuanhua', 'Yuan, Yadong', 'Cheng, Zhaozhong', 'Liang, Lirong', 'Dai, Huaping', 'Huang, Kewu', 'Lu, Weixuan', 'Zhang, Zhonghe', 'Cheng, Xiansheng', 'Shen, Ying H', None]",Respir Res,,,True
8f5fc8690f47c0c30dd99bd8d84f9e80f25fdcc8,PMC,Influenza H5N1 and H1N1 Virus Replication and Innate Immune Responses in Bronchial Epithelial Cells Are Influenced by the State of Differentiation,http://dx.doi.org/10.1371/journal.pone.0008713,PMC2806912,20090947,CC BY,"Influenza H5N1 virus continues to be enzootic in poultry and transmits zoonotically to humans. Although a swine-origin H1N1 virus has emerged to become pandemic, its virulence for humans remains modest in comparison to that seen in zoonotic H5N1 disease. As human respiratory epithelium is the primary target cells for influenza viruses, elucidating the viral tropism and host innate immune responses of influenza H5N1 virus in human bronchial epithelium may help to understand the pathogenesis. Here we established primary culture of undifferentiated and well differentiated normal human bronchial epithelial (NHBE) cells and infected with highly pathogenic influenza H5N1 virus (A/Vietnam/3046/2004) and a seasonal influenza H1N1 virus (A/Hong Kong/54/1998), the viral replication kinetics and cytokine and chemokine responses were compared by qPCR and ELISA. We found that the in vitro culture of the well differentiated NHBE cells acquired the physiological properties of normal human bronchi tissue which express high level of α2-6-linked sialic acid receptors and human airway trypsin-like (HAT) protease, in contrast to the low expression in the non-differentiated NHBE cells. When compared to H1N1 virus, the H5N1 virus replicated more efficiently and induced a stronger type I interferon response in the undifferentiated NHBE cells. In contrast, in well differentiated cultures, H5N1 virus replication was less efficient and elicited a lower interferon-beta response in comparison with H1N1 virus. Our data suggest that the differentiation of bronchial epithelial cells has a major influence in cells' permissiveness to human H1N1 and avian H5N1 viruses and the host innate immune responses. The reduced virus replication efficiency partially accounts for the lower interferon-beta responses in influenza H5N1 virus infected well differentiated NHBE cells. Since influenza infection in the bronchial epithelium will lead to tissue damage and associate with the epithelium regeneration, the data generated from the undifferentiated NHBE cultures may also be relevant to disease pathogenesis.",2010 Jan 15,"['Chan, Renee W. Y.', 'Yuen, Kit M.', 'Yu, Wendy C. L.', 'Ho, Carol C. C.', 'Nicholls, John M.', 'Peiris, J. S. Malik', 'Chan, Michael C. W.']",PLoS One,,,True
0e23b62f7dca85c31f4f90603d2a28dfc7177947,PMC,Dynamic Innate Immune Responses of Human Bronchial Epithelial Cells to Severe Acute Respiratory Syndrome-Associated Coronavirus Infection,http://dx.doi.org/10.1371/journal.pone.0008729,PMC2806919,20090954,CC BY,"Human lung epithelial cells are likely among the first targets to encounter invading severe acute respiratory syndrome-associated coronavirus (SARS-CoV). Not only can these cells support the growth of SARS-CoV infection, but they are also capable of secreting inflammatory cytokines to initiate and, eventually, aggravate host innate inflammatory responses, causing detrimental immune-mediated pathology within the lungs. Thus, a comprehensive evaluation of the complex epithelial signaling to SARS-CoV is crucial for paving the way to better understand SARS pathogenesis. Based on microarray-based functional genomics, we report here the global gene response of 2B4 cells, a cloned bronchial epithelial cell line derived from Calu-3 cells. Specifically, we found a temporal and spatial activation of nuclear factor (NF)κB, activator protein (AP)-1, and interferon regulatory factor (IRF)-3/7 in infected 2B4 cells at 12-, 24-, and 48-hrs post infection (p.i.), resulting in the activation of many antiviral genes, including interferon (IFN)-β, -λs, inflammatory mediators, and many IFN-stimulated genes (ISGs). We also showed, for the first time, that IFN-β and IFN-λs were capable of exerting previously unrecognized, non-redundant, and complementary abilities to limit SARS-CoV replication, even though their expression could not be detected in infected 2B4 bronchial epithelial cells until 48 hrs p.i. Collectively, our results highlight the mechanics of the sequential events of antiviral signaling pathway/s triggered by SARS-CoV in bronchial epithelial cells and identify novel cellular targets for future studies, aiming at advancing strategies against SARS.",2010 Jan 15,"['Yoshikawa, Tomoki', 'Hill, Terence E.', 'Yoshikawa, Naoko', 'Popov, Vsevolod L.', 'Galindo, Cristi L.', 'Garner, Harold R.', 'Peters, C. J.', 'Tseng, Chien-Te (Kent)']",PLoS One,,,True
31b6292728805572de28133c6eb02ed1d44ef211,PMC,Automated Detection of Conformational Epitopes Using Phage Display Peptide Sequences,,PMC2808184,20140073,CC BY,"BACKGROUND: Precise determination of conformational epitopes of neutralizing antibodies represents a key step in the rational design of novel vaccines. A powerful experimental method to gain insights on the physical chemical nature of conformational epitopes is the selection of linear peptides that bind with high affinities to a monoclonal antibody of interest by phage display technology. However, the structural characterization of conformational epitopes from these mimotopes is not straightforward, and in the past the interpretation of peptide sequences from phage display experiments focused on linear sequence analysis to find a consensus sequence or common sequence motifs. RESULTS: We present a fully automated search method, EpiSearch that predicts the possible location of conformational epitopes on the surface of an antigen. The algorithm uses peptide sequences from phage display experiments as input, and ranks all surface exposed patches according to the frequency distribution of similar residues in the peptides and in the patch. We have tested the performance of the EpiSearch algorithm for six experimental data sets of phage display experiments, the human epidermal growth factor receptor-2 (HER-2/neu), the antibody mAb Bo2C11 targeting the C(2) domain of FVIII, antibodies mAb 17b and mAb b12 of the HIV envelope protein gp120, mAb 13b5 targeting HIV-1 capsid protein and 80R of the SARS coronavirus spike protein. In all these examples the conformational epitopes as determined by the X-ray crystal structures of the antibody-antigen complexes, were found within the highest scoring patches of EpiSearch, covering in most cases more than 50% residues of experimental observed conformational epitopes. Input options of the program include mapping of a single peptide or a set of peptides on the antigen structure, and the results of the calculation can be visualized on our interactive web server. AVAILABILITY: Users can access the EpiSearch from our web server http://curie.utmb.edu/episearch.html",2009 Jul 1,"['Negi, Surendra S', 'Braun, Werner']",Bioinform Biol Insights,,,True
7a4c5c15a8bbf8fdb5694b2ce8aaf72991784476,PMC,Quantifying the impact of community quarantine on SARS transmission in Ontario: estimation of secondary case count difference and number needed to quarantine,http://dx.doi.org/10.1186/1471-2458-9-488,PMC2808319,20034405,CC BY,"BACKGROUND: Community quarantine is controversial, and the decision to use and prepare for it should be informed by specific quantitative evidence of benefit. Case-study reports on 2002-2004 SARS outbreaks have discussed the role of quarantine in the community in transmission. However, this literature has not yielded quantitative estimates of the reduction in secondary cases attributable to quarantine as would be seen in other areas of health policy and cost-effectiveness analysis. METHODS: Using data from the 2003 Ontario, Canada, SARS outbreak, two novel expressions for the impact of quarantine are presented. Secondary Case Count Difference (SCCD) reflects reduction in the average number of transmissions arising from a SARS case in quarantine, relative to not in quarantine, at onset of symptoms. SCCD was estimated using Poisson and negative binomial regression models (with identity link function) comparing the number of secondary cases to each index case for quarantine relative to non-quarantined index cases. The inverse of this statistic is proposed as the number needed to quarantine (NNQ) to prevent one additional secondary transmission. RESULTS: Our estimated SCCD was 0.133 fewer secondary cases per quarantined versus non-quarantined index case; and a NNQ of 7.5 exposed individuals to be placed in community quarantine to prevent one additional case of transmission in the community. This analysis suggests quarantine can be an effective preventive measure, although these estimates lack statistical precision. CONCLUSIONS: Relative to other health policy areas, literature on quarantine tends to lack in quantitative expressions of effectiveness, or agreement on how best to report differences in outcomes attributable to control measure. We hope to further this discussion through presentation of means to calculate and express the impact of population control measures. The study of quarantine effectiveness presents several methodological and statistical challenges. Further research and discussion are needed to understand the costs and benefits of enacting quarantine, and this includes a discussion of how quantitative benefit should be communicated to decision-makers and the public, and evaluated.",2009 Dec 24,"['Bondy, Susan J', 'Russell, Margaret L', 'Laflèche, Julie ML', 'Rea, Elizabeth']",BMC Public Health,,,True
88d360849c4d9dddb7c9d16db3e9c4bbb52b7b75,PMC,Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals,http://dx.doi.org/10.1371/journal.pone.0008805,PMC2808385,20098712,CC BY,"BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.",2010 Jan 20,"['Corti, Davide', 'Langedijk, Johannes P. M.', 'Hinz, Andreas', 'Seaman, Michael S.', 'Vanzetta, Fabrizia', 'Fernandez-Rodriguez, Blanca M.', 'Silacci, Chiara', 'Pinna, Debora', 'Jarrossay, David', 'Balla-Jhagjhoorsingh, Sunita', 'Willems, Betty', 'Zekveld, Maria J.', 'Dreja, Hanna', ""O'Sullivan, Eithne"", 'Pade, Corinna', 'Orkin, Chloe', 'Jeffs, Simon A.', 'Montefiori, David C.', 'Davis, David', 'Weissenhorn, Winfried', 'McKnight, Áine', 'Heeney, Jonathan L.', 'Sallusto, Federica', 'Sattentau, Quentin J.', 'Weiss, Robin A.', 'Lanzavecchia, Antonio']",PLoS One,,,True
7bfb92f7dd06c758acfeecdccf82ccc541e7a250,PMC,Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals,http://dx.doi.org/10.1371/journal.pone.0008805,PMC2808385,20098712,CC BY,"BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.",2010 Jan 20,"['Corti, Davide', 'Langedijk, Johannes P. M.', 'Hinz, Andreas', 'Seaman, Michael S.', 'Vanzetta, Fabrizia', 'Fernandez-Rodriguez, Blanca M.', 'Silacci, Chiara', 'Pinna, Debora', 'Jarrossay, David', 'Balla-Jhagjhoorsingh, Sunita', 'Willems, Betty', 'Zekveld, Maria J.', 'Dreja, Hanna', ""O'Sullivan, Eithne"", 'Pade, Corinna', 'Orkin, Chloe', 'Jeffs, Simon A.', 'Montefiori, David C.', 'Davis, David', 'Weissenhorn, Winfried', 'McKnight, Áine', 'Heeney, Jonathan L.', 'Sallusto, Federica', 'Sattentau, Quentin J.', 'Weiss, Robin A.', 'Lanzavecchia, Antonio']",PLoS One,,,False
96b7cea86d9ad33fc927ddd3662c4283d0bb1aa7,PMC,Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals,http://dx.doi.org/10.1371/journal.pone.0008805,PMC2808385,20098712,CC BY,"BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.",2010 Jan 20,"['Corti, Davide', 'Langedijk, Johannes P. M.', 'Hinz, Andreas', 'Seaman, Michael S.', 'Vanzetta, Fabrizia', 'Fernandez-Rodriguez, Blanca M.', 'Silacci, Chiara', 'Pinna, Debora', 'Jarrossay, David', 'Balla-Jhagjhoorsingh, Sunita', 'Willems, Betty', 'Zekveld, Maria J.', 'Dreja, Hanna', ""O'Sullivan, Eithne"", 'Pade, Corinna', 'Orkin, Chloe', 'Jeffs, Simon A.', 'Montefiori, David C.', 'Davis, David', 'Weissenhorn, Winfried', 'McKnight, Áine', 'Heeney, Jonathan L.', 'Sallusto, Federica', 'Sattentau, Quentin J.', 'Weiss, Robin A.', 'Lanzavecchia, Antonio']",PLoS One,,,False
c5c5caecb4512142fc02aaad1c784183ae424d42,PMC,Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals,http://dx.doi.org/10.1371/journal.pone.0008805,PMC2808385,20098712,CC BY,"BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.",2010 Jan 20,"['Corti, Davide', 'Langedijk, Johannes P. M.', 'Hinz, Andreas', 'Seaman, Michael S.', 'Vanzetta, Fabrizia', 'Fernandez-Rodriguez, Blanca M.', 'Silacci, Chiara', 'Pinna, Debora', 'Jarrossay, David', 'Balla-Jhagjhoorsingh, Sunita', 'Willems, Betty', 'Zekveld, Maria J.', 'Dreja, Hanna', ""O'Sullivan, Eithne"", 'Pade, Corinna', 'Orkin, Chloe', 'Jeffs, Simon A.', 'Montefiori, David C.', 'Davis, David', 'Weissenhorn, Winfried', 'McKnight, Áine', 'Heeney, Jonathan L.', 'Sallusto, Federica', 'Sattentau, Quentin J.', 'Weiss, Robin A.', 'Lanzavecchia, Antonio']",PLoS One,,,False
012bbad97aa874f5f32645d80cee5526db164dd1,PMC,Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals,http://dx.doi.org/10.1371/journal.pone.0008805,PMC2808385,20098712,CC BY,"BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.",2010 Jan 20,"['Corti, Davide', 'Langedijk, Johannes P. M.', 'Hinz, Andreas', 'Seaman, Michael S.', 'Vanzetta, Fabrizia', 'Fernandez-Rodriguez, Blanca M.', 'Silacci, Chiara', 'Pinna, Debora', 'Jarrossay, David', 'Balla-Jhagjhoorsingh, Sunita', 'Willems, Betty', 'Zekveld, Maria J.', 'Dreja, Hanna', ""O'Sullivan, Eithne"", 'Pade, Corinna', 'Orkin, Chloe', 'Jeffs, Simon A.', 'Montefiori, David C.', 'Davis, David', 'Weissenhorn, Winfried', 'McKnight, Áine', 'Heeney, Jonathan L.', 'Sallusto, Federica', 'Sattentau, Quentin J.', 'Weiss, Robin A.', 'Lanzavecchia, Antonio']",PLoS One,,,False
dccd778c1e8d73adf7919681c1b0ff95395646f8,PMC,Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals,http://dx.doi.org/10.1371/journal.pone.0008805,PMC2808385,20098712,CC BY,"BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.",2010 Jan 20,"['Corti, Davide', 'Langedijk, Johannes P. M.', 'Hinz, Andreas', 'Seaman, Michael S.', 'Vanzetta, Fabrizia', 'Fernandez-Rodriguez, Blanca M.', 'Silacci, Chiara', 'Pinna, Debora', 'Jarrossay, David', 'Balla-Jhagjhoorsingh, Sunita', 'Willems, Betty', 'Zekveld, Maria J.', 'Dreja, Hanna', ""O'Sullivan, Eithne"", 'Pade, Corinna', 'Orkin, Chloe', 'Jeffs, Simon A.', 'Montefiori, David C.', 'Davis, David', 'Weissenhorn, Winfried', 'McKnight, Áine', 'Heeney, Jonathan L.', 'Sallusto, Federica', 'Sattentau, Quentin J.', 'Weiss, Robin A.', 'Lanzavecchia, Antonio']",PLoS One,,,False
19127add559e55feb42f8f2f97cda34f2d1e631e,PMC,Analysis of Memory B Cell Responses and Isolation of Novel Monoclonal Antibodies with Neutralizing Breadth from HIV-1-Infected Individuals,http://dx.doi.org/10.1371/journal.pone.0008805,PMC2808385,20098712,CC BY,"BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.",2010 Jan 20,"['Corti, Davide', 'Langedijk, Johannes P. M.', 'Hinz, Andreas', 'Seaman, Michael S.', 'Vanzetta, Fabrizia', 'Fernandez-Rodriguez, Blanca M.', 'Silacci, Chiara', 'Pinna, Debora', 'Jarrossay, David', 'Balla-Jhagjhoorsingh, Sunita', 'Willems, Betty', 'Zekveld, Maria J.', 'Dreja, Hanna', ""O'Sullivan, Eithne"", 'Pade, Corinna', 'Orkin, Chloe', 'Jeffs, Simon A.', 'Montefiori, David C.', 'Davis, David', 'Weissenhorn, Winfried', 'McKnight, Áine', 'Heeney, Jonathan L.', 'Sallusto, Federica', 'Sattentau, Quentin J.', 'Weiss, Robin A.', 'Lanzavecchia, Antonio']",PLoS One,,,False
95d6b47d51b17a1f41ab4df0ed64086ebc11e589,PMC,Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza,http://dx.doi.org/10.1186/cc8208,PMC2811892,20003352,CC BY,"INTRODUCTION: Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. METHODS: We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. RESULTS: Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1β), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-γ) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-α, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. CONCLUSIONS: While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.",2009 Dec 11,"['Bermejo-Martin, Jesus F', 'Ortiz de Lejarazu, Raul', 'Pumarola, Tomas', 'Rello, Jordi', 'Almansa, Raquel', 'Ramírez, Paula', 'Martin-Loeches, Ignacio', 'Varillas, David', 'Gallegos, Maria C', 'Serón, Carlos', 'Micheloud, Dariela', 'Gomez, Jose Manuel', 'Tenorio-Abreu, Alberto', 'Ramos, María J', 'Molina, M Lourdes', 'Huidobro, Samantha', 'Sanchez, Elia', 'Gordón, Mónica', 'Fernández, Victoria', 'del Castillo, Alberto', 'Marcos, Ma Ángeles', 'Villanueva, Beatriz', 'López, Carlos Javier', 'Rodríguez-Domínguez, Mario', 'Galan, Juan-Carlos', 'Cantón, Rafael', 'Lietor, Aurora', 'Rojo, Silvia', 'Eiros, Jose M', 'Hinojosa, Carmen', 'Gonzalez, Isabel', 'Torner, Nuria', 'Banner, David', 'Leon, Alberto', 'Cuesta, Pablo', 'Rowe, Thomas', 'Kelvin, David J']",Crit Care,,,True
02783b0989ab6a54fd4af139d787b69b9d9d009e,PMC,"Single Assay for Simultaneous Detection and Differential Identification of Human and Avian Influenza Virus Types, Subtypes, and Emergent Variants",http://dx.doi.org/10.1371/journal.pone.0008995,PMC2815781,20140251,CC0,"For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence, host-range, and resistance to antiviral agents.",2010 Feb 3,"['Metzgar, David', 'Myers, Christopher A.', 'Russell, Kevin L.', 'Faix, Dennis', 'Blair, Patrick J.', 'Brown, Jason', 'Vo, Scott', 'Swayne, David E.', 'Thomas, Colleen', 'Stenger, David A.', 'Lin, Baochuan', 'Malanoski, Anthony P.', 'Wang, Zheng', 'Blaney, Kate M.', 'Long, Nina C.', 'Schnur, Joel M.', 'Saad, Magdi D.', 'Borsuk, Lisa A.', 'Lichanska, Agnieszka M.', 'Lorence, Matthew C.', 'Weslowski, Brian', 'Schafer, Klaus O.', 'Tibbetts, Clark']",PLoS One,,,True
284790100b67133f3228466016a8f98ad096e24d,PMC,Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates,http://dx.doi.org/10.1371/journal.ppat.1000756,PMC2816697,20140198,CC BY,"The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.",2010 Feb 5,"['Smits, Saskia L.', 'de Lang, Anna', 'van den Brand, Judith M. A.', 'Leijten, Lonneke M.', 'van IJcken, Wilfred F.', 'Eijkemans, Marinus J. C.', 'van Amerongen, Geert', 'Kuiken, Thijs', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.']",PLoS Pathog,,,True
e2dd36baf975d279561e30fc21893f93dc006c24,PMC,Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates,http://dx.doi.org/10.1371/journal.ppat.1000756,PMC2816697,20140198,CC BY,"The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.",2010 Feb 5,"['Smits, Saskia L.', 'de Lang, Anna', 'van den Brand, Judith M. A.', 'Leijten, Lonneke M.', 'van IJcken, Wilfred F.', 'Eijkemans, Marinus J. C.', 'van Amerongen, Geert', 'Kuiken, Thijs', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.']",PLoS Pathog,,,False
89cef46c775f7e515544ba4e7c937a9793dabbc9,PMC,Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates,http://dx.doi.org/10.1371/journal.ppat.1000756,PMC2816697,20140198,CC BY,"The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.",2010 Feb 5,"['Smits, Saskia L.', 'de Lang, Anna', 'van den Brand, Judith M. A.', 'Leijten, Lonneke M.', 'van IJcken, Wilfred F.', 'Eijkemans, Marinus J. C.', 'van Amerongen, Geert', 'Kuiken, Thijs', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.']",PLoS Pathog,,,False
706e03d60c9ad429bc4c10195e0bc4adf189a409,PMC,Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates,http://dx.doi.org/10.1371/journal.ppat.1000756,PMC2816697,20140198,CC BY,"The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.",2010 Feb 5,"['Smits, Saskia L.', 'de Lang, Anna', 'van den Brand, Judith M. A.', 'Leijten, Lonneke M.', 'van IJcken, Wilfred F.', 'Eijkemans, Marinus J. C.', 'van Amerongen, Geert', 'Kuiken, Thijs', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.']",PLoS Pathog,,,False
cd9172cf6716c4ea412f4faefa5209cef6d403fb,PMC,Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates,http://dx.doi.org/10.1371/journal.ppat.1000756,PMC2816697,20140198,CC BY,"The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.",2010 Feb 5,"['Smits, Saskia L.', 'de Lang, Anna', 'van den Brand, Judith M. A.', 'Leijten, Lonneke M.', 'van IJcken, Wilfred F.', 'Eijkemans, Marinus J. C.', 'van Amerongen, Geert', 'Kuiken, Thijs', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.']",PLoS Pathog,,,False
808ff5aadc2181b9993ff7c050b4db8bd7f9625c,PMC,Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates,http://dx.doi.org/10.1371/journal.ppat.1000756,PMC2816697,20140198,CC BY,"The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.",2010 Feb 5,"['Smits, Saskia L.', 'de Lang, Anna', 'van den Brand, Judith M. A.', 'Leijten, Lonneke M.', 'van IJcken, Wilfred F.', 'Eijkemans, Marinus J. C.', 'van Amerongen, Geert', 'Kuiken, Thijs', 'Andeweg, Arno C.', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.']",PLoS Pathog,,,False
513d5ea4db4eb8e94c14c46b018c6041d78119cf,PMC,IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity,http://dx.doi.org/10.1371/journal.ppat.1000757,PMC2816698,20140199,CC BY,"The innate immune response is essential for controlling West Nile virus (WNV) infection but how this response is propagated and regulates adaptive immunity in vivo are not defined. Herein, we show that IPS-1, the central adaptor protein to RIG-I-like receptor (RLR) signaling, is essential for triggering of innate immunity and for effective development and regulation of adaptive immunity against pathogenic WNV. IPS-1(−/−) mice exhibited increased susceptibility to WNV infection marked by enhanced viral replication and dissemination with early viral entry into the CNS. Infection of cultured bone-marrow (BM) derived dendritic cells (DCs), macrophages (Macs), and primary cortical neurons showed that the IPS-1-dependent RLR signaling was essential for triggering IFN defenses and controlling virus replication in these key target cells of infection. Intriguingly, infected IPS-1(−/−) mice displayed uncontrolled inflammation that included elevated systemic type I IFN, proinflammatory cytokine and chemokine responses, increased numbers of inflammatory DCs, enhanced humoral responses marked by complete loss of virus neutralization activity, and increased numbers of virus-specific CD8+ T cells and non-specific immune cell proliferation in the periphery and in the CNS. This uncontrolled inflammatory response was associated with a lack of regulatory T cell expansion that normally occurs during acute WNV infection. Thus, the enhanced inflammatory response in the absence of IPS-1 was coupled with a failure to protect against WNV infection. Our data define an innate/adaptive immune interface mediated through IPS-1-dependent RLR signaling that regulates the quantity, quality, and balance of the immune response to WNV infection.",2010 Feb 5,"['Suthar, Mehul S.', 'Ma, Daphne Y.', 'Thomas, Sunil', 'Lund, Jennifer M.', 'Zhang, Nu', 'Daffis, Stephane', 'Rudensky, Alexander Y.', 'Bevan, Michael J.', 'Clark, Edward A.', 'Kaja, Murali-Krishna', 'Diamond, Michael S.', 'Gale, Michael']",PLoS Pathog,,,True
10abe76a05511196ea1f252383f0c70d592e7444,PMC,New Class of Monoclonal Antibodies against Severe Influenza: Prophylactic and Therapeutic Efficacy in Ferrets,http://dx.doi.org/10.1371/journal.pone.0009106,PMC2817000,20161706,CC BY,"BACKGROUND: The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes) has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage. CONCLUSIONS/SIGNIFICANCE: These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza.",2010 Feb 8,"['Friesen, Robert H. E.', 'Koudstaal, Wouter', 'Koldijk, Martin H.', 'Weverling, Gerrit Jan', 'Brakenhoff, Just P. J.', 'Lenting, Peter J.', 'Stittelaar, Koert J.', 'Osterhaus, Albert D. M. E.', 'Kompier, Ronald', 'Goudsmit, Jaap']",PLoS One,,,True
0768babd4f340cc1b5eb49540be3decfc480eb8b,PMC,Synonymous Codon Usage Analysis of Thirty Two Mycobacteriophage Genomes,http://dx.doi.org/10.1155/2009/316936,PMC2817497,20150956,CC BY,"Synonymous codon usage of protein coding genes of thirty two completely sequenced mycobacteriophage genomes was studied using multivariate statistical analysis. One of the major factors influencing codon usage is identified to be compositional bias. Codons ending with either C or G are preferred in highly expressed genes among which C ending codons are highly preferred over G ending codons. A strong negative correlation between effective number of codons (Nc) and GC3s content was also observed, showing that the codon usage was effected by gene nucleotide composition. Translational selection is also identified to play a role in shaping the codon usage operative at the level of translational accuracy. High level of heterogeneity is seen among and between the genomes. Length of genes is also identified to influence the codon usage in 11 out of 32 phage genomes. Mycobacteriophage Cooper is identified to be the highly biased genome with better translation efficiency comparing well with the host specific tRNA genes.",2009 Feb 1,"['Hassan, Sameer', 'Mahalingam, Vasantha', 'Kumar, Vanaja']",Adv Bioinformatics,,,True
cafc9ffe47534a504ae1036e5b7299d80f49beb5,PMC,Paleovirology—Modern Consequences of Ancient Viruses,http://dx.doi.org/10.1371/journal.pbio.1000301,PMC2817711,20161719,CC BY,,2010 Feb 9,"['Emerman, Michael', 'Malik, Harmit S.']",PLoS Biol,,,True
b0a17b1f4447f0a81d2e93f2e23720feadee96cd,PMC,Mathematical Modeling of the Effectiveness of Facemasks in Reducing the Spread of Novel Influenza A (H1N1),http://dx.doi.org/10.1371/journal.pone.0009018,PMC2818714,20161764,CC BY,"On June 11, 2009, the World Health Organization declared the outbreak of novel influenza A (H1N1) a pandemic. With limited supplies of antivirals and vaccines, countries and individuals are looking at other ways to reduce the spread of pandemic (H1N1) 2009, particularly options that are cost effective and relatively easy to implement. Recent experiences with the 2003 SARS and 2009 H1N1 epidemics have shown that people are willing to wear facemasks to protect themselves against infection; however, little research has been done to quantify the impact of using facemasks in reducing the spread of disease. We construct and analyze a mathematical model for a population in which some people wear facemasks during the pandemic and quantify impact of these masks on the spread of influenza. To estimate the parameter values used for the effectiveness of facemasks, we used available data from studies on N95 respirators and surgical facemasks. The results show that if N95 respirators are only 20% effective in reducing susceptibility and infectivity, only 10% of the population would have to wear them to reduce the number of influenza A (H1N1) cases by 20%. We can conclude from our model that, if worn properly, facemasks are an effective intervention strategy in reducing the spread of pandemic (H1N1) 2009.",2010 Feb 10,"['Tracht, Samantha M.', 'Del Valle, Sara Y.', 'Hyman, James M.']",PLoS One,,,True
aa8a9f4a432fa52294b1fa674b3ffbeadeff563f,PMC,Human Coronavirus NL63 Open Reading Frame 3 encodes a virion-incorporated N-glycosylated membrane protein,http://dx.doi.org/10.1186/1743-422X-7-6,PMC2819038,20078868,CC BY,"BACKGROUND: Human pathogenic coronavirus NL63 (hCoV-NL63) is a group 1 (alpha) coronavirus commonly associated with respiratory tract infections. In addition to known non-structural and structural proteins all coronaviruses have one or more accessory proteins whose functions are mostly unknown. Our study focuses on hCoV-NL63 open reading frame 3 (ORF 3) which is a highly conserved accessory protein among coronaviruses. RESULTS: In-silico analysis of the 225 amino acid sequence of hCoV-NL63 ORF 3 predicted a triple membrane-spanning protein. Expression in infected CaCo-2 and LLC-MK2 cells was confirmed by immunofluorescence and Western blot analysis. The protein was detected within the endoplasmatic reticulum/Golgi intermediate compartment (ERGIC) where coronavirus assembly and budding takes place. Subcellular localization studies using recombinant ORF 3 protein transfected in Huh-7 cells revealed occurrence in ERGIC, Golgi- and lysosomal compartments. By fluorescence microscopy of differently tagged envelope (E), membrane (M) and nucleocapsid (N) proteins it was shown that ORF 3 protein colocalizes extensively with E and M within the ERGIC. Using N-terminally FLAG-tagged ORF 3 protein and an antiserum specific to the C-terminus we verified the proposed topology of an extracellular N-terminus and a cytosolic C-terminus. By in-vitro translation analysis and subsequent endoglycosidase H digestion we showed that ORF 3 protein is N-glycosylated at the N-terminus. Analysis of purified viral particles revealed that ORF 3 protein is incorporated into virions and is therefore an additional structural protein. CONCLUSIONS: This study is the first extensive expression analysis of a group 1 hCoV-ORF 3 protein. We give evidence that ORF 3 protein is a structural N-glycosylated and virion-incorporated protein.",2010 Jan 15,"['Müller, Marcel A', 'van der Hoek, Lia', 'Voss, Daniel', 'Bader, Oliver', 'Lehmann, Dörte', 'Schulz, Axel R', 'Kallies, Stephan', 'Suliman, Tasnim', 'Fielding, Burtram C', 'Drosten, Christian', 'Niedrig, Matthias']",Virol J,,,True
fe1dea09375e7ab4f239b5c57cd522fc05ff3e37,PMC,"Avian Colibacillosis and Salmonellosis: A Closer Look at Epidemiology, Pathogenesis, Diagnosis, Control and Public Health Concerns",http://dx.doi.org/10.3390/ijerph7010089,PMC2819778,20195435,CC BY,"Avian colibacillosis and salmonellosis are considered to be the major bacterial diseases in the poultry industry world-wide. Colibacillosis and salmonellosis are the most common avian diseases that are communicable to humans. This article provides the vital information on the epidemiology, pathogenesis, diagnosis, control and public health concerns of avian colibacillosis and salmonellosis. A better understanding of the information addressed in this review article will assist the poultry researchers and the poultry industry in continuing to make progress in reducing and eliminating avian colibacillosis and salmonellosis from the poultry flocks, thereby reducing potential hazards to the public health posed by these bacterial diseases.",2010 Jan 12,"Lutful Kabir, S. M.",Int J Environ Res Public Health,,,True
e4d6c7b63c33ac798572f0e53ab6b53a2f71b452,PMC,Correcting the Actual Reproduction Number: A Simple Method to Estimate R(0) from Early Epidemic Growth Data,http://dx.doi.org/10.3390/ijerph7010291,PMC2819789,20195446,CC BY,"The basic reproduction number, R(0), a summary measure of the transmission potential of an infectious disease, is estimated from early epidemic growth rate, but a likelihood-based method for the estimation has yet to be developed. The present study corrects the concept of the actual reproduction number, offering a simple framework for estimating R(0) without assuming exponential growth of cases. The proposed method is applied to the HIV epidemic in European countries, yielding R(0) values ranging from 3.60 to 3.74, consistent with those based on the Euler-Lotka equation. The method also permits calculating the expected value of R(0) using a spreadsheet.",2010 Jan 21,"Nishiura, Hiroshi",Int J Environ Res Public Health,,,True
c41cd165529d51d5418e2628ceda43970f8ca399,PMC,Evidence that Gag facilitates HIV-1 envelope association both in GPI-enriched plasma membrane and detergent resistant membranes and facilitates envelope incorporation onto virions in primary CD4(+ )T cells,http://dx.doi.org/10.1186/1743-422X-7-3,PMC2820015,20064199,CC BY,"HIV-1 particle assembly mediated by viral Gag protein occurs predominantly at plasma membrane. While colocalization of HIV-1 envelope with lipid rich microenvironment have been shown in T cells, the significance of viral proteins modulating envelope association in such microdomains in plasma membrane enriched in glycosylphosphatidylinositol-anchored proteins in primary CD4(+ )T cells that are natural targets of HIV-1 is poorly understood. Here we show that in primary CD4(+ )T cells that are natural targets of HIV-1 in vivo, Gag modulates HIV-1 envelope association with GM1 ganglioside and CD59 rich cellular compartments as well as with detergent resistant membranes. Our data strengthen evidence that Gag-Env interaction is important in envelope association with lipid rafts containing GPI-anchored proteins for efficient assembly onto mature virions resulting in productive infection of primary CD4(+ )T cells.",2010 Jan 8,"['Patil, Ajit', 'Gautam, Archana', 'Bhattacharya, Jayanta']",Virol J,,,True
1cf0ff471514dc73eaa490d65d0d4a35f1345f6e,PMC,"Novel Virus Influenza A (H1N1sw) in South-Eastern France, April-August 2009",http://dx.doi.org/10.1371/journal.pone.0009214,PMC2822845,20174643,CC BY,"BACKGROUND: In April 2009, the first cases of pandemic (H1N1)-2009 influenza [H1N1sw] virus were detected in France. Virological surveillance was undertaken in reference laboratories of the seven French Defence Zones. METHODOLOGY/PRINCIPAL FINDINGS: We report results of virological analyses performed in the Public Hospitals of Marseille during the first months of the outbreak. (i) Nasal swabs were tested using rapid influenza diagnostic test (RIDT) and two RT-PCR assays. Epidemiological characteristics of the 99 first suspected cases were analyzed, including detection of influenza virus and 18 other respiratory viruses. During three months, a total of 1,815 patients were tested (including 236 patients infected H1N1sw virus) and distribution in age groups and results of RIDT were analyzed. (ii) 600 sera received before April 2009 and randomly selected from in-patients were tested by a standard hemagglutination inhibition assay for antibody to the novel H1N1sw virus. (iii) One early (May 2009) and one late (July 2009) viral isolates were characterized by sequencing the complete hemagglutinine and neuraminidase genes. (iiii) Epidemiological characteristics of a cluster of cases that occurred in July 2009 in a summer camp were analyzed. CONCLUSIONS/SIGNIFICANCE: This study presents new virological and epidemiological data regarding infection by the pandemic A/H1N1 virus in Europe. Distribution in age groups was found to be similar to that previously reported for seasonal H1N1. The first seroprevalence data made available for a European population suggest a previous exposure of individuals over 40 years old to influenza viruses antigenically related to the pandemic (H1N1)-2009 virus. Genomic analysis indicates that strains harbouring a new amino-acid pattern in the neuraminidase gene appeared secondarily and tended to supplant the first strains. Finally, in contrast with previous reports, our data support the use of RIDT for the detection of infection in children, especially in the context of the investigation of grouped cases.",2010 Feb 17,"['Nougairède, Antoine', 'Ninove, Laetitia', 'Zandotti, Christine', 'Salez, Nicolas', 'Mantey, Karine', 'Resseguier, Noémie', 'Gazin, Céline', 'Raoult, Didier', 'Charrel, Rémi N.', 'de Lamballerie, Xavier']",PLoS One,,,True
e5db7954926b0072fa6bf086899e4faf42c15f3a,PMC,An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses,http://dx.doi.org/10.1186/1743-422X-7-9,PMC2823673,20082709,CC BY,"BACKGROUND: A growing concern has raised regarding the pandemic potential of the highly pathogenic avian influenza (HPAI) H5N1 viruses. Consequently, there is an urgent need to develop an effective and safe vaccine against the divergent H5N1 influenza viruses. In the present study, we designed a tetra-branched multiple antigenic peptide (MAP)-based vaccine, designated M2e-MAP, which contains the sequence overlapping the highly conserved extracellular domain of matrix protein 2 (M2e) of a HPAI H5N1 virus, and investigated its immune responses and cross-protection against different clades of H5N1 viruses. RESULTS: Our results showed that M2e-MAP vaccine induced strong M2e-specific IgG antibody responses following 3-dose immunization of mice with M2e-MAP in the presence of Freunds' or aluminium (alum) adjuvant. M2e-MAP vaccination limited viral replication and attenuated histopathological damage in the challenged mouse lungs. The M2e-MAP-based vaccine protected immunized mice against both clade1: VN/1194 and clade2.3.4: SZ/406H H5N1 virus challenge, being able to counteract weight lost and elevate survival rate following lethal challenge of H5N1 viruses. CONCLUSIONS: These results suggest that M2e-MAP presenting M2e of H5N1 virus has a great potential to be developed into an effective subunit vaccine for the prevention of infection by a broad spectrum of HPAI H5N1 viruses.",2010 Jan 18,"['Zhao, Guangyu', 'Lin, Yongping', 'Du, Lanying', 'Guan, Jie', 'Sun, Shihui', 'Sui, Hongyan', 'Kou, Zhihua', 'Chan, Chris CS', 'Guo, Yan', 'Jiang, Shibo', 'Zheng, Bo-Jian', 'Zhou, Yusen']",Virol J,,,True
3568da162b8d9f5356c9264193b6292efa3d9556,PMC,Arterivirus Nsp1 Modulates the Accumulation of Minus-Strand Templates to Control the Relative Abundance of Viral mRNAs,http://dx.doi.org/10.1371/journal.ppat.1000772,PMC2824749,20174607,CC BY,"The gene expression of plus-strand RNA viruses with a polycistronic genome depends on translation and replication of the genomic mRNA, as well as synthesis of subgenomic (sg) mRNAs. Arteriviruses and coronaviruses, distantly related members of the nidovirus order, employ a unique mechanism of discontinuous minus-strand RNA synthesis to generate subgenome-length templates for the synthesis of a nested set of sg mRNAs. Non-structural protein 1 (nsp1) of the arterivirus equine arteritis virus (EAV), a multifunctional regulator of viral RNA synthesis and virion biogenesis, was previously implicated in controlling the balance between genome replication and sg mRNA synthesis. Here, we employed reverse and forward genetics to gain insight into the multiple regulatory roles of nsp1. Our analysis revealed that the relative abundance of viral mRNAs is tightly controlled by an intricate network of interactions involving all nsp1 subdomains. Distinct nsp1 mutations affected the quantitative balance among viral mRNA species, and our data implicate nsp1 in controlling the accumulation of full-length and subgenome-length minus-strand templates for viral mRNA synthesis. The moderate differential changes in viral mRNA abundance of nsp1 mutants resulted in similarly altered viral protein levels, but progeny virus yields were greatly reduced. Pseudorevertant analysis provided compelling genetic evidence that balanced EAV mRNA accumulation is critical for efficient virus production. This first report on protein-mediated, mRNA-specific control of nidovirus RNA synthesis reveals the existence of an integral control mechanism to fine-tune replication, sg mRNA synthesis, and virus production, and establishes a major role for nsp1 in coordinating the arterivirus replicative cycle.",2010 Feb 19,"['Nedialkova, Danny D.', 'Gorbalenya, Alexander E.', 'Snijder, Eric J.']",PLoS Pathog,,,True
d9e06d074df536664275030a32f54ff8d8bb0361,PMC,The Disulfide Bonds in Glycoprotein E2 of Hepatitis C Virus Reveal the Tertiary Organization of the Molecule,http://dx.doi.org/10.1371/journal.ppat.1000762,PMC2824758,20174556,CC BY,"Hepatitis C virus (HCV), a major cause of chronic liver disease in humans, is the focus of intense research efforts worldwide. Yet structural data on the viral envelope glycoproteins E1 and E2 are scarce, in spite of their essential role in the viral life cycle. To obtain more information, we developed an efficient production system of recombinant E2 ectodomain (E2e), truncated immediately upstream its trans-membrane (TM) region, using Drosophila melanogaster cells. This system yields a majority of monomeric protein, which can be readily separated chromatographically from contaminating disulfide-linked aggregates. The isolated monomeric E2e reacts with a number of conformation-sensitive monoclonal antibodies, binds the soluble CD81 large external loop and efficiently inhibits infection of Huh7.5 cells by infectious HCV particles (HCVcc) in a dose-dependent manner, suggesting that it adopts a native conformation. These properties of E2e led us to experimentally determine the connectivity of its 9 disulfide bonds, which are strictly conserved across HCV genotypes. Furthermore, circular dichroism combined with infrared spectroscopy analyses revealed the secondary structure contents of E2e, indicating in particular about 28% β-sheet, in agreement with the consensus secondary structure predictions. The disulfide connectivity pattern, together with data on the CD81 binding site and reported E2 deletion mutants, enabled the threading of the E2e polypeptide chain onto the structural template of class II fusion proteins of related flavi- and alphaviruses. The resulting model of the tertiary organization of E2 gives key information on the antigenicity determinants of the virus, maps the receptor binding site to the interface of domains I and III, and provides insight into the nature of a putative fusogenic conformational change.",2010 Feb 19,"['Krey, Thomas', ""d'Alayer, Jacques"", 'Kikuti, Carlos M.', 'Saulnier, Aure', 'Damier-Piolle, Laurence', 'Petitpas, Isabelle', 'Johansson, Daniel X.', 'Tawar, Rajiv G.', 'Baron, Bruno', 'Robert, Bruno', 'England, Patrick', 'Persson, Mats A. A.', 'Martin, Annette', 'Rey, Félix A.']",PLoS Pathog,,,True
d819ba39c114acf69059a2d37f21246f30edaf56,PMC,The Disulfide Bonds in Glycoprotein E2 of Hepatitis C Virus Reveal the Tertiary Organization of the Molecule,http://dx.doi.org/10.1371/journal.ppat.1000762,PMC2824758,20174556,CC BY,"Hepatitis C virus (HCV), a major cause of chronic liver disease in humans, is the focus of intense research efforts worldwide. Yet structural data on the viral envelope glycoproteins E1 and E2 are scarce, in spite of their essential role in the viral life cycle. To obtain more information, we developed an efficient production system of recombinant E2 ectodomain (E2e), truncated immediately upstream its trans-membrane (TM) region, using Drosophila melanogaster cells. This system yields a majority of monomeric protein, which can be readily separated chromatographically from contaminating disulfide-linked aggregates. The isolated monomeric E2e reacts with a number of conformation-sensitive monoclonal antibodies, binds the soluble CD81 large external loop and efficiently inhibits infection of Huh7.5 cells by infectious HCV particles (HCVcc) in a dose-dependent manner, suggesting that it adopts a native conformation. These properties of E2e led us to experimentally determine the connectivity of its 9 disulfide bonds, which are strictly conserved across HCV genotypes. Furthermore, circular dichroism combined with infrared spectroscopy analyses revealed the secondary structure contents of E2e, indicating in particular about 28% β-sheet, in agreement with the consensus secondary structure predictions. The disulfide connectivity pattern, together with data on the CD81 binding site and reported E2 deletion mutants, enabled the threading of the E2e polypeptide chain onto the structural template of class II fusion proteins of related flavi- and alphaviruses. The resulting model of the tertiary organization of E2 gives key information on the antigenicity determinants of the virus, maps the receptor binding site to the interface of domains I and III, and provides insight into the nature of a putative fusogenic conformational change.",2010 Feb 19,"['Krey, Thomas', ""d'Alayer, Jacques"", 'Kikuti, Carlos M.', 'Saulnier, Aure', 'Damier-Piolle, Laurence', 'Petitpas, Isabelle', 'Johansson, Daniel X.', 'Tawar, Rajiv G.', 'Baron, Bruno', 'Robert, Bruno', 'England, Patrick', 'Persson, Mats A. A.', 'Martin, Annette', 'Rey, Félix A.']",PLoS Pathog,,,True
e9bcf05233a1b2f6b7a37e98d950ee976ae592e1,PMC,The Disulfide Bonds in Glycoprotein E2 of Hepatitis C Virus Reveal the Tertiary Organization of the Molecule,http://dx.doi.org/10.1371/journal.ppat.1000762,PMC2824758,20174556,CC BY,"Hepatitis C virus (HCV), a major cause of chronic liver disease in humans, is the focus of intense research efforts worldwide. Yet structural data on the viral envelope glycoproteins E1 and E2 are scarce, in spite of their essential role in the viral life cycle. To obtain more information, we developed an efficient production system of recombinant E2 ectodomain (E2e), truncated immediately upstream its trans-membrane (TM) region, using Drosophila melanogaster cells. This system yields a majority of monomeric protein, which can be readily separated chromatographically from contaminating disulfide-linked aggregates. The isolated monomeric E2e reacts with a number of conformation-sensitive monoclonal antibodies, binds the soluble CD81 large external loop and efficiently inhibits infection of Huh7.5 cells by infectious HCV particles (HCVcc) in a dose-dependent manner, suggesting that it adopts a native conformation. These properties of E2e led us to experimentally determine the connectivity of its 9 disulfide bonds, which are strictly conserved across HCV genotypes. Furthermore, circular dichroism combined with infrared spectroscopy analyses revealed the secondary structure contents of E2e, indicating in particular about 28% β-sheet, in agreement with the consensus secondary structure predictions. The disulfide connectivity pattern, together with data on the CD81 binding site and reported E2 deletion mutants, enabled the threading of the E2e polypeptide chain onto the structural template of class II fusion proteins of related flavi- and alphaviruses. The resulting model of the tertiary organization of E2 gives key information on the antigenicity determinants of the virus, maps the receptor binding site to the interface of domains I and III, and provides insight into the nature of a putative fusogenic conformational change.",2010 Feb 19,"['Krey, Thomas', ""d'Alayer, Jacques"", 'Kikuti, Carlos M.', 'Saulnier, Aure', 'Damier-Piolle, Laurence', 'Petitpas, Isabelle', 'Johansson, Daniel X.', 'Tawar, Rajiv G.', 'Baron, Bruno', 'Robert, Bruno', 'England, Patrick', 'Persson, Mats A. A.', 'Martin, Annette', 'Rey, Félix A.']",PLoS Pathog,,,False
b85794a3749932e7585c864b7fbb766f38dd97f6,PMC,Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach,http://dx.doi.org/10.1371/journal.pgen.1000849,PMC2824813,20174570,CC BY,"Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driven selective pressure. Results showed an excess of variants correlated with virus diversity in genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors; a significantly higher than expected number of variants was also seen in genes encoding proteins that directly interact with viral components. Genome-wide analyses identified 441 variants significantly associated with virus-diversity; these are more frequently located within gene regions than expected, and they map to 139 human genes. Analysis of functional relationships among genes subjected to virus-driven selective pressure identified a complex network enriched in viral products-interacting proteins. The novel approach to the study of infectious disease epidemiology presented herein may represent an alternative to classic genome-wide association studies and provides a large set of candidate susceptibility variants for viral infections.",2010 Feb 19,"['Fumagalli, Matteo', 'Pozzoli, Uberto', 'Cagliani, Rachele', 'Comi, Giacomo P.', 'Bresolin, Nereo', 'Clerici, Mario', 'Sironi, Manuela']",PLoS Genet,,,True
0d543b40bcecd9573a4dbe14f2231f48554da3c1,PMC,Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach,http://dx.doi.org/10.1371/journal.pgen.1000849,PMC2824813,20174570,CC BY,"Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driven selective pressure. Results showed an excess of variants correlated with virus diversity in genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors; a significantly higher than expected number of variants was also seen in genes encoding proteins that directly interact with viral components. Genome-wide analyses identified 441 variants significantly associated with virus-diversity; these are more frequently located within gene regions than expected, and they map to 139 human genes. Analysis of functional relationships among genes subjected to virus-driven selective pressure identified a complex network enriched in viral products-interacting proteins. The novel approach to the study of infectious disease epidemiology presented herein may represent an alternative to classic genome-wide association studies and provides a large set of candidate susceptibility variants for viral infections.",2010 Feb 19,"['Fumagalli, Matteo', 'Pozzoli, Uberto', 'Cagliani, Rachele', 'Comi, Giacomo P.', 'Bresolin, Nereo', 'Clerici, Mario', 'Sironi, Manuela']",PLoS Genet,,,False
c5519427a4559ac86ef69166403d0c2e9a90b690,PMC,Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach,http://dx.doi.org/10.1371/journal.pgen.1000849,PMC2824813,20174570,CC BY,"Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driven selective pressure. Results showed an excess of variants correlated with virus diversity in genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors; a significantly higher than expected number of variants was also seen in genes encoding proteins that directly interact with viral components. Genome-wide analyses identified 441 variants significantly associated with virus-diversity; these are more frequently located within gene regions than expected, and they map to 139 human genes. Analysis of functional relationships among genes subjected to virus-driven selective pressure identified a complex network enriched in viral products-interacting proteins. The novel approach to the study of infectious disease epidemiology presented herein may represent an alternative to classic genome-wide association studies and provides a large set of candidate susceptibility variants for viral infections.",2010 Feb 19,"['Fumagalli, Matteo', 'Pozzoli, Uberto', 'Cagliani, Rachele', 'Comi, Giacomo P.', 'Bresolin, Nereo', 'Clerici, Mario', 'Sironi, Manuela']",PLoS Genet,,,False
ec3316b6d33659c1070099a4395a1c25eeacc446,PMC,"Triple Combination of Amantadine, Ribavirin, and Oseltamivir Is Highly Active and Synergistic against Drug Resistant Influenza Virus Strains In Vitro",http://dx.doi.org/10.1371/journal.pone.0009332,PMC2825274,20179772,CC0,"The rapid emergence and subsequent spread of the novel 2009 Influenza A/H1N1 virus (2009 H1N1) has prompted the World Health Organization to declare the first pandemic of the 21(st) century, highlighting the threat of influenza to public health and healthcare systems. Widespread resistance to both classes of influenza antivirals (adamantanes and neuraminidase inhibitors) occurs in both pandemic and seasonal viruses, rendering these drugs to be of marginal utility in the treatment modality. Worldwide, virtually all 2009 H1N1 and seasonal H3N2 strains are resistant to the adamantanes (rimantadine and amantadine), and the majority of seasonal H1N1 strains are resistant to oseltamivir, the most widely prescribed neuraminidase inhibitor (NAI). To address the need for more effective therapy, we evaluated the in vitro activity of a triple combination antiviral drug (TCAD) regimen composed of drugs with different mechanisms of action against drug-resistant seasonal and 2009 H1N1 influenza viruses. Amantadine, ribavirin, and oseltamivir, alone and in combination, were tested against amantadine- and oseltamivir-resistant influenza A viruses using an in vitro infection model in MDCK cells. Our data show that the triple combination was highly synergistic against drug-resistant viruses, and the synergy of the triple combination was significantly greater than the synergy of any double combination tested (P<0.05), including the combination of two NAIs. Surprisingly, amantadine and oseltamivir contributed to the antiviral activity of the TCAD regimen against amantadine- and oseltamivir-resistant viruses, respectively, at concentrations where they had no activity as single agents, and at concentrations that were clinically achievable. Our data demonstrate that the TCAD regimen composed of amantadine, ribavirin, and oseltamivir is highly synergistic against resistant viruses, including 2009 H1N1. The TCAD regimen overcomes baseline drug resistance to both classes of approved influenza antivirals, and thus may represent a highly active antiviral therapy for seasonal and pandemic influenza.",2010 Feb 22,"['Nguyen, Jack T.', 'Hoopes, Justin D.', 'Le, Minh H.', 'Smee, Donald F.', 'Patick, Amy K.', 'Faix, Dennis J.', 'Blair, Patrick J.', 'de Jong, Menno D.', 'Prichard, Mark N.', 'Went, Gregory T.']",PLoS One,,,True
165d5a3cf0dc10f8229b0c6fcf149cd244cbd73a,PMC,Evolution and emergence of novel human infections,http://dx.doi.org/10.1098/rspb.2009.1059,PMC2825776,19692402,CC BY,"Some zoonotic pathogens cause sporadic infection in humans but rarely propagate further, while others have succeeded in overcoming the species barrier and becoming established in the human population. Adaptation, driven by selection pressure in human hosts, can play a significant role in allowing pathogens to cross this species barrier. Here we use a simple mathematical model to study potential epidemiological markers of adaptation. We ask: under what circumstances could ongoing adaptation be signalled by large clusters of human infection? If a pathogen has caused hundreds of cases but with little transmission, does this indicate that the species barrier cannot be crossed? Finally, how can case reports be monitored to detect an imminent emergence event? We distinguish evolutionary scenarios under which adaptation is likely to be signalled by large clusters of infection and under which emergence is likely to occur without any prior warning. Moreover, we show that a lack of transmission never rules out adaptability, regardless of how many zoonoses have occurred. Indeed, after the first 100 zoonotic cases, continuing sporadic zoonotic infections without onward, human-to-human transmission offer little extra information on pathogen adaptability. Finally, we present a simple method for monitoring outbreaks for signs of emergence and discuss public health implications.",2009 Nov 22,"['Arinaminpathy, N.', 'McLean, A. R.']",Proc Biol Sci,,,True
f5dd178e6cfe607d118df9d16716cd68605dbee4,PMC,The Feasibility of Canine Rabies Elimination in Africa: Dispelling Doubts with Data,http://dx.doi.org/10.1371/journal.pntd.0000626,PMC2826407,20186330,CC BY,"BACKGROUND: Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent. METHODOLOGY/PRINCIPAL FINDINGS: This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention. CONCLUSIONS/SIGNIFICANCE: We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths.",2010 Feb 23,"['Lembo, Tiziana', 'Hampson, Katie', 'Kaare, Magai T.', 'Ernest, Eblate', 'Knobel, Darryn', 'Kazwala, Rudovick R.', 'Haydon, Daniel T.', 'Cleaveland, Sarah']",PLoS Negl Trop Dis,,,True
3ebd3fb346c40a654f1f9d8e48ef8daa1902d406,PMC,Descriptive distribution and phylogenetic analysis of feline infectious peritonitis virus isolates of Malaysia,http://dx.doi.org/10.1186/1751-0147-52-1,PMC2828449,20053278,CC BY,"The descriptive distribution and phylogeny of feline coronaviruses (FCoVs) were studied in cats suspected of having feline infectious peritonitis (FIP) in Malaysia. Ascitic fluids and/or biopsy samples were subjected to a reverse transcription polymerase chain reaction (RT-PCR) targeted for a conserved region of 3'untranslated region (3'UTR) of the FCoV genome. Eighty nine percent of the sampled animals were positive for the presence of FCoV. Among the FCoV positive cats, 80% of cats were males and 64% were below 2 years of age. The FCoV positive cases included 56% domestic short hair (DSH), 40% Persian, and 4% Siamese cats. The nucleotide sequences of 10 selected amplified products from FIP cases were determined. The sequence comparison revealed that the field isolates had 96% homology with a few point mutations. The extent of homology decreased to 93% when compared with reference strains. The overall branching pattern of phylogenetic tree showed two distinct clusters, where all Malaysian isolates fall into one main genetic cluster. These findings provided the first genetic information of FCoV in Malaysia.",2010 Jan 6,"['Sharif, Saeed', 'Arshad, Siti S', 'Hair-Bejo, Mohd', 'Omar, Abdul R', 'Zeenathul, Nazariah A', 'Fong, Lau S', 'Rahman, Nor-Alimah', 'Arshad, Habibah', 'Shamsudin, Shahirudin', 'Isa, Mohd-Kamarudin A']",Acta Vet Scand,,,True
c92099607cfae94a24e03a111d12994535cc2eae,PMC,A new therapeutic strategy for lung tissue injury induced by influenza with CR2 targeting complement inhibitior,http://dx.doi.org/10.1186/1743-422X-7-30,PMC2829536,20144216,CC BY,"BACKGROUND: Influenza is a respiratory disease that seriously threatens human health. In fact, influenza virus itself does not make critical contribution to mortality induced by influenza, but ""cytokine storm"" produced by the excessive immune response triggered by the virus can result in inflammatory reaction of lung tissues and fatal lung tissue injury, and thus increase influenza mortality. Therefore, besides antiviral drugs, immunosuppression drugs should also be included in infection treatment. PRESENTATION OF THE HYPOTHESIS: Complement is the center of inflammatory reaction. If complement system is over activated, the body will have strong inflammatory reaction or tissue injury, resulting in pathological process. Many studies have proved that, inflammatory injury of lung tissues caused by influenza virus is closely related to complement activation. Therefore, inhibiting complement activation can significantly reduce inflammatory injury in lung tissues. As complement is both a physiological defense and pathological damage medium, systematic inhibition may result in side effects including infection. Therefore, we design targeting complement inhibitors for complement activation sites, i.e. with CR2 as targeting vector, complement inhibitors like CD59 and Crry are targeted to inflammatory sites to specially inhibit the complement activation in local injury, thus local inflammatory reaction is inhibited. TESTING THE HYPOTHESIS: CR2-CD59 and CR2-Crry targeting complement inhibitors are fusion-expressed, and their biological activity is examined via in vivo and in vitro tests. CR2 targeting complement inhibitors are used to treat mouse influenza viral pneumonia model, with PBS treatment group as the control. The survival and lung tissue injury of the mice is observed and the effect of CR2 targeting complement inhibitors on pneumonia induced by influenza virus is evaluated. IMPLICATIONS OF THE HYPOTHESIS: CR2 targeting complement inhibitors are expected to be ideal drugs for viral pneumonia.",2010 Feb 9,"['Zhang, Chuanfu', 'Xu, Yuanyong', 'Jia, Leili', 'Yang, Yutao', 'Wang, Yong', 'Sun, Yansong', 'Huang, Liuyu', 'Qiao, Fei', 'Tomlinson, Stephen', 'Liu, Xuelin', 'Zhou, Yusen', 'Song, Hongbin']",Virol J,,,True
b187316c24eb26f96af6ebbc243e90cfc504d94b,PMC,High-level expression and purification of soluble recombinant FGF21 protein by SUMO fusion in Escherichia coli,http://dx.doi.org/10.1186/1472-6750-10-14,PMC2831817,20163718,CC BY,"BACKGROUND: Fibroblast growth factor 21 (FGF21) is a promising drug candidate to combat metabolic diseases. However, high-level expression and purification of recombinant FGF21 (rFGF21) in Escherichia coli (E. coli) is difficult because rFGF21 forms inclusion bodies in the bacteria making it difficult to purify and obtain high concentrations of bioactive rFGF21. To overcome this problem, we fused the FGF21 with SUMO (Small ubiquitin-related modifier) by polymerase chain reaction (PCR), and expressed the fused gene in E. coli BL21(DE3). RESULTS: By inducing with IPTG, SUMO-FGF21 was expressed at a high level. Its concentration reached 30% of total protein, and exceeded 95% of all soluble proteins. The fused protein was purified by DEAE sepharose FF and Ni-NTA affinity chromatography. Once cleaved by the SUMO protease, the purity of rFGF21 by high performance liquid chromatography (HPLC) was shown to be higher than 96% with low endotoxin level (<1.0 EU/ml). The results of in vivo animal experiments showed that rFGF21 produced by using this method, could decrease the concentration of plasma glucose in diabetic rats by streptozotocin (STZ) injection. CONCLUSIONS: This study demonstrated that SUMO, when fused with FGF21, was able to promote its soluble expression of the latter in E. coli, making it more convenient to purify rFGF21 than previously. This may be a better method to produce rFGF21 for pharmaceutical research and development.",2010 Feb 17,"['Wang, Huiyan', 'Xiao, Yechen', 'Fu, Lianjun', 'Zhao, Hongxin', 'Zhang, Yaofang', 'Wan, Xiaoshan', 'Qin, Yuxia', 'Huang, Yadong', 'Gao, Hongchang', 'Li, Xiaokun']",BMC Biotechnol,,,True
6f94dde3cf8c2776d869b8490fb491d7416088f0,PMC,Surveillance of febrile patients in a district and evaluation of their spatiotemporal associations: a pilot study,http://dx.doi.org/10.1186/1471-2458-10-84,PMC2831836,20170529,CC BY,"BACKGROUND: Fever is an undifferentiated clinical feature that may enhance the sensitivity of syndromic surveillance systems. By studying the spatiotemporal associations of febrile patients, it may allow early detection of case clustering that indicates imminent threat of infectious disease outbreaks in the community. METHODS: We captured consecutive emergency department visits that led to hospitalization in a district hospital in Hong Kong during the period of 12 Sep 2005 to 14 Oct 2005. We recorded demographic data, provisional diagnoses, temperature on presentation and residential location for each patient-episode, and geocoded the residential addresses. We applied Geographical Information System technology to study the geographical distribution these cases, and their associations within a 50-m buffer zone spatially. A case cluster was defined by three or more spatially associated febrile patients within each three consecutive days. RESULTS: One thousand and sixty six patient-episodes were eligible for analysis; 42% of them had fever (>37°C; oral temperature) on presentation. Two hundred and four patient-episodes (19.1%) came from residential care homes for elderly (RCHE). We detected a total of 40 case clusters during the study period. Clustered cases were of older age; 57 (33.3%) were residents of RCHE. We found a median of 3 patients (range: 3 - 8) and time span of 3 days (range: 2 - 8 days) in each cluster. Twenty five clusters had 2 or more patients living in the same building block; 18 of them were from RCHE. CONCLUSIONS: It is technically feasible to perform surveillance on febrile patients and studying their spatiotemporal associations. The information is potentially useful for early detection of impending infectious disease threats.",2010 Feb 20,"['Choi, Kin-wing', 'Wong, Ngai-sze', 'Lee, Lap-yip', 'Lee, Shui-shan']",BMC Public Health,,,True
4b3e454f57edd89563485c04da1df5f95ebd2b5e,PMC,SARS coronavirus protein 7a interacts with human Ap(4)A-hydrolase,http://dx.doi.org/10.1186/1743-422X-7-31,PMC2831879,20144233,CC BY,"The SARS coronavirus (SARS-CoV) open reading frame 7a (ORF 7a) encodes a 122 amino acid accessory protein. It has no significant sequence homology with any other known proteins. The 7a protein is present in the virus particle and has been shown to interact with several host proteins; thereby implicating it as being involved in several pathogenic processes including apoptosis, inhibition of cellular protein synthesis, and activation of p38 mitogen activated protein kinase. In this study we present data demonstrating that the SARS-CoV 7a protein interacts with human Ap(4)A-hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17). Ap(4)A-hydrolase is responsible for metabolizing the ""allarmone"" nucleotide Ap(4)A and therefore likely involved in regulation of cell proliferation, DNA replication, RNA processing, apoptosis and DNA repair. The interaction between 7a and Ap(4)A-hydrolase was identified using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation from cultured human cells transiently expressing V5-His tagged 7a and HA tagged Ap(4)A-hydrolase. Human tissue culture cells transiently expressing 7a and Ap(4)A-hydrolase tagged with EGFP and Ds-Red2 respectively show these proteins co-localize in the cytoplasm.",2010 Feb 9,"['Vasilenko, Natalia', 'Moshynskyy, Igor', 'Zakhartchouk, Alexander']",Virol J,,,True
f4714dd09f8ab317ec688ba087e67239b2b93367,PMC,Coevolution of activating and inhibitory receptors within mammalian carcinoembryonic antigen families,http://dx.doi.org/10.1186/1741-7007-8-12,PMC2832619,20132533,CC BY,"BACKGROUND: Most rapidly evolving gene families are involved in immune responses and reproduction, two biological functions which have been assigned to the carcinoembryonic antigen (CEA) gene family. To gain insights into evolutionary forces shaping the CEA gene family we have analysed this gene family in 27 mammalian species including monotreme and marsupial lineages. RESULTS: Phylogenetic analysis provided convincing evidence that the primordial CEA gene family in mammals consisted of five genes, including the immune inhibitory receptor-encoding CEACAM1 (CEA-related cell adhesion molecule) ancestor. Our analysis of the substitution rates within the nucleotide sequence which codes for the ligand binding domain of CEACAM1 indicates that the selection for diversification is, perhaps, a consequence of the exploitation of CEACAM1 by a variety of viral and bacterial pathogens as their cellular receptor. Depending on the extent of the amplification of an ancestral CEACAM1, the number of CEACAM1-related genes varies considerably between mammalian species from less than five in lagomorphs to more than 100 in bats. In most analysed species, ITAM (immunoreceptor tyrosine-based activation motifs) or ITAM-like motif-containing proteins exist which contain Ig-V-like, ligand binding domains closely related to that of CEACAM1. Human CEACAM3 is one such protein which can function as a CEACAM1 decoy receptor in granulocytes by mediating the uptake and destruction of specific bacterial pathogens via its ITAM-like motif. The close relationship between CEACAM1 and its ITAM-encoding relatives appears to be maintained by gene conversion and reciprocal recombination. Surprisingly, secreted CEACAMs resembling immunomodulatory CEACAM1-related trophoblast-specific pregnancy-specific glycoproteins (PSGs) found in humans and rodents evolved only in a limited set of mammals. The appearance of PSG-like genes correlates with invasive trophoblast growth in these species. CONCLUSIONS: These phylogenetic studies provide evidence that pathogen/host coevolution and a possible participation in fetal-maternal conflict processes led to a highly species-specific diversity of mammalian CEA gene families.",2010 Feb 4,"['Kammerer, Robert', 'Zimmermann, Wolfgang']",BMC Biol,,,True
f72764a9a0f911eb892cf04752566d6ef4ee54c4,PMC,Binding of Herpes Simplex Virus Type-1 Virions Leads to the Induction of Intracellular Signalling in the Absence of Virus Entry,http://dx.doi.org/10.1371/journal.pone.0009560,PMC2832691,20221426,CC BY,"The envelope of HSV-1 contains a number of glycoproteins, four of which are essential for virus entry. Virus particles lacking gB, gD, gH or gL are entry-defective, although these viruses retain the ability to bind to the plasma membrane via the remaining glycoproteins. Soluble forms of gD have been shown to trigger the nuclear translocation of the NF-κB transcriptional complex in addition to stimulating the production of Type I interferon. By taking advantage of the entry-defective phenotype of glycoprotein-deficient HSV-1 virus particles, the results presented here show that binding of virions to cellular receptors on the plasma membrane is sufficient to stimulate a change in cellular gene expression. Preliminary microarray studies, validated by quantitative real-time PCR, identified the differential expression of cellular genes associated with the NF-κB, PI3K/Akt, Jak/Stat and related Jak/Src pathways by virions lacking gB or gH but not gD. Gene induction occurred at a few particles per cell, corresponding to physiological conditions during primary infection. Reporter assay studies determined that NF-κB transcriptional activity is stimulated within an hour of HSV-1 binding, peaks between two and three hours post-binding and declines to background levels by five hours after induction. The immediate, transient nature of these signalling events suggests that HSV-1 glycoproteins, particularly gD, may alter the cellular environment pre-entry so as to condition the cell for viral replication.",2010 Mar 5,"['MacLeod, Iain J.', 'Minson, Tony']",PLoS One,,,True
9f7729a11b54369146911c3ce8d0d9a299925080,PMC,Binding of Herpes Simplex Virus Type-1 Virions Leads to the Induction of Intracellular Signalling in the Absence of Virus Entry,http://dx.doi.org/10.1371/journal.pone.0009560,PMC2832691,20221426,CC BY,"The envelope of HSV-1 contains a number of glycoproteins, four of which are essential for virus entry. Virus particles lacking gB, gD, gH or gL are entry-defective, although these viruses retain the ability to bind to the plasma membrane via the remaining glycoproteins. Soluble forms of gD have been shown to trigger the nuclear translocation of the NF-κB transcriptional complex in addition to stimulating the production of Type I interferon. By taking advantage of the entry-defective phenotype of glycoprotein-deficient HSV-1 virus particles, the results presented here show that binding of virions to cellular receptors on the plasma membrane is sufficient to stimulate a change in cellular gene expression. Preliminary microarray studies, validated by quantitative real-time PCR, identified the differential expression of cellular genes associated with the NF-κB, PI3K/Akt, Jak/Stat and related Jak/Src pathways by virions lacking gB or gH but not gD. Gene induction occurred at a few particles per cell, corresponding to physiological conditions during primary infection. Reporter assay studies determined that NF-κB transcriptional activity is stimulated within an hour of HSV-1 binding, peaks between two and three hours post-binding and declines to background levels by five hours after induction. The immediate, transient nature of these signalling events suggests that HSV-1 glycoproteins, particularly gD, may alter the cellular environment pre-entry so as to condition the cell for viral replication.",2010 Mar 5,"['MacLeod, Iain J.', 'Minson, Tony']",PLoS One,,,False
02e34b2fe0968cb8a46313fe767858da7e2691b1,PMC,"Candidates in Astroviruses, Seadornaviruses, Cytorhabdoviruses and Coronaviruses for +1 frame overlapping genes accessed by leaky scanning",http://dx.doi.org/10.1186/1743-422X-7-17,PMC2832772,20100346,CC BY,"BACKGROUND: Overlapping genes are common in RNA viruses where they serve as a mechanism to optimize the coding potential of compact genomes. However, annotation of overlapping genes can be difficult using conventional gene-finding software. Recently we have been using a number of complementary approaches to systematically identify previously undetected overlapping genes in RNA virus genomes. In this article we gather together a number of promising candidate new overlapping genes that may be of interest to the community. RESULTS: Overlapping gene predictions are presented for the astroviruses, seadornaviruses, cytorhabdoviruses and coronaviruses (families Astroviridae, Reoviridae, Rhabdoviridae and Coronaviridae, respectively).",2010 Jan 25,"['Firth, Andrew E', 'Atkins, John F']",Virol J,,,True
b9b85a4893f9ed75881adcedbf142098bd7edc93,PMC,Thermal stability and inactivation of hepatitis C virus grown in cell culture,http://dx.doi.org/10.1186/1743-422X-7-40,PMC2834657,20167059,CC BY,"BACKGROUND: Hepatitis C virus (HCV) is a blood-borne flavivirus that infects many millions of people worldwide. Relatively little is known, however, concerning the stability of HCV and reliable procedures for inactivating this virus. METHODS: In the current study, the thermostability of cell culture-derived HCV (HCVcc, JFH-1 strain) under different environmental temperatures (37°C, room temperature, and 4°C) and the ability of heat, UVC light irradiation, and aldehyde and detergent treatments to inactivate HCVcc were evaluated. The infectious titers of treated viral samples were determined by focus-forming unit (FFU) assay using an indirect immunofluorescence assay for HCV NS3 in hepatoma Huh7-25-CD81 cells highly permissive for HCVcc infection. MTT cytotoxicity assay was performed to determine the concentrations of aldehydes or detergents at which they were no longer cytotoxic. RESULTS: HCVcc in culture medium was found to survive 37°C and room temperature (RT, 25 ± 2°C) for 2 and 16 days, respectively, while the virus was relatively stable at 4°C without drastic loss of infectivity for at least 6 weeks. HCVcc in culture medium was sensitive to heat and could be inactivated in 8 and 4 min when incubated at 60°C and 65°C, respectively. However, at 56°C, 40 min were required to eliminate HCVcc infectivity. Addition of normal human serum to HCVcc did not significantly alter viral stability at RT or its susceptibility to heat. UVC light irradiation (wavelength = 253.7 nm) with an intensity of 450 μW/cm(2 )efficiently inactivated HCVcc within 2 min. Exposures to formaldehyde, glutaraldehyde, ionic or nonionic detergents all destroyed HCVcc infectivity effectively, regardless of whether the treatments were conducted in the presence of cell culture medium or human serum. CONCLUSIONS: The results provide quantitative evidence for the potential use of a variety of approaches for inactivating HCV. The ability of HCVcc to survive ambient temperatures warrants precautions in handling and disposing of objects and materials that may have been contaminated with HCV.",2010 Feb 18,"['Song, Hongshuo', 'Li, Jin', 'Shi, Shuang', 'Yan, Ling', 'Zhuang, Hui', 'Li, Kui']",Virol J,,,True
9fdb08f94d250800ca69a84cb21c110adbe1476b,PMC,"New Approaches to Preventing, Diagnosing, and Treating Neonatal Sepsis",http://dx.doi.org/10.1371/journal.pmed.1000213,PMC2834705,20231868,CC BY,Karen Edmond and Anita Zaidi highlight new approaches that could reduce the burden of neonatal sepsis worldwide.,2010 Mar 9,"['Edmond, Karen', 'Zaidi, Anita']",PLoS Med,,,True
af10fafcbc7f54b2c2cf780db5ccf5a2b4a1c985,PMC,Murine Coronavirus Cell Type Dependent Interaction with the Type I Interferon Response,http://dx.doi.org/10.3390/v1030689,PMC2835314,20221421,CC BY,"Coronaviruses infect many species of animal including humans, causing acute and chronic diseases of many organ systems. Murine coronavirus, mouse hepatitis virus (MHV) infection of the mouse, provides animal models for the study of central nervous system disease, including encephalitis and demyelinating diseases such as Multiple Sclerosis and for hepatitis. While there are many studies of the adaptive immune response to MHV, there has until recently been scant information on the type I interferon (IFN) response to MHV. The relationship between MHV and the IFN-α/β response is paradoxical. While the type I IFN response is a crucial aspect of host defense against MHV in its natural host, there is little if any induction of IFN following infection of mouse fibroblast cell lines in vitro. Furthermore, MHV is relatively resistant to the antiviral effects of IFN-α/β in mouse fibroblast cell lines and in human 293T cells. MHV can, under some circumstances, compromise the antiviral effects of IFN signaling. The nucleocapsid protein as well as the nsp1 and nsp3 proteins of MHV has been reported to have IFN antagonist activity. However, in primary cell types such as plasmacytoid dendritic cells (pDC) and macrophages, IFN is induced by MHV infection and an antiviral state is established. Other primary cell types such as neurons, astrocytes and hepatocytes fail to produce IFN following infection and, in vivo, likely depend on IFN produced by pDCs and macrophages for protection from MHV. Thus MHV induction of IFN-α/β and the ability to induce an antiviral state in response to interferon is extremely cell type dependent. IFN induced protection from MHV pathogenesis likely requires the orchestrated activities of several cell types, however, the cell types involved in limiting MHV replication may be different in the liver and in the immune privileged CNS.",2009 Nov 4,"['Rose, Kristine M.', 'Weiss, Susan R.']",Viruses,,,True
0ddcebebb542f8a0905a3cf82a59f404158d3de2,PMC,Simultaneous Detection of CDC Category “A” DNA and RNA Bioterrorism Agents by Use of Multiplex PCR & RT-PCR Enzyme Hybridization Assays,http://dx.doi.org/10.3390/v1030441,PMC2836126,20224751,CC BY,"Assays to simultaneously detect multiple potential agents of bioterrorism are limited. Two multiplex PCR and RT-PCR enzyme hybridization assays (mPCR-EHA, mRT-PCR-EHA) were developed to simultaneously detect many of the CDC category “A” bioterrorism agents. The “Bio T” DNA assay was developed to detect: Variola major (VM), Bacillus anthracis (BA), Yersinia pestis (YP), Francisella tularensis (FT) and Varicella zoster virus (VZV). The “Bio T” RNA assay (mRT-PCR-EHA) was developed to detect: Ebola virus (Ebola), Lassa fever virus (Lassa), Rift Valley fever (RVF), Hantavirus Sin Nombre species (HSN) and dengue virus (serotypes 1–4). Sensitivity and specificity of the 2 assays were tested by using genomic DNA, recombinant plasmid positive controls, RNA transcripts controls, surrogate (spiked) clinical samples and common respiratory pathogens. The analytical sensitivity (limit of detection (LOD)) of the DNA asssay for genomic DNA was 1×10(0)∼1×10(2) copies/mL for BA, FT and YP. The LOD for VZV whole organism was 1×10(−2) TCID(50)/mL. The LOD for recombinant controls ranged from 1×10(2)∼1×10(3)copies/mL for BA, FT, YP and VM. The RNA assay demonstrated LOD for RNA transcript controls of 1×10(4)∼1×10(6) copies/mL without extraction and 1×10(5)∼1×10(6) copies/mL with extraction for Ebola, RVF, Lassa and HSN. The LOD for dengue whole organisms was ∼1×10(−4) dilution for dengue 1 and 2, 1×10(4) LD(50)/mL and 1×10(2) LD(50)/mL for dengue 3 and 4. The LOD without extraction for recombinant plasmid DNA controls was ∼1×10(3) copies/mL (1.5 input copies/reaction) for Ebola, RVF, Lassa and HSN. No cross-reactivity of primers and probes used in both assays was detected with common respiratory pathogens or between targeted analytes. Clinical sensitivity was estimated using 264 surrogate clinical samples tested with the BioT DNA assay and 549 samples tested with the BioT RNA assay. The clinical specificity is 99.6% and 99.8% for BioT DNA assay and BioT RNA assay, respectively. The surrogate sensitivities of these two assays were 100% (95%CI 83–100) for FT, BA (pX02), YP, VM, VZV, dengue 2,3,4 and 95% (95%CI 75–100) for BA (pX01) and dengue 1 using spiked clinical specimens. The specificity of both BioT multiplex assays on spiked specimens was 100% (95% CI 99–100). Compared to other available assays (culture, serology, PCR, etc.) both the BioT DNA mPCR-EHA and BioT RNA mRT-PCR-EHA are rapid, sensitive and specific assays for detecting many category “A” Bioterrorism agents using a standard thermocycler.",2009 Oct 20,"['He, Jie', 'Kraft, Andrea J.', 'Fan, Jiang', 'Van Dyke, Meredith', 'Wang, Lihua', 'Bose, Michael E.', 'Khanna, Marilyn', 'Metallo, Jacob A.', 'Henrickson, Kelly J.']",Viruses,,,True
f8243fd9214e2e45a222a43aad977d882f17e1e9,PMC,Computational analysis and determination of a highly conserved surface exposed segment in H5N1 avian flu and H1N1 swine flu neuraminidase,http://dx.doi.org/10.1186/1472-6807-10-6,PMC2836360,20170556,CC BY,"BACKGROUND: Catalytic activity of influenza neuraminidase (NA) facilitates elution of progeny virions from infected cells and prevents their self-aggregation mediated by the catalytic site located in the body region. Research on the active site of the molecule has led to development of effective inhibitors like oseltamivir, zanamivir etc, but the high rate of mutation and interspecies reassortment in viral sequences and the recent reports of oseltamivir resistant strains underlines the importance of determining additional target sites for developing future antiviral compounds. In a recent computational study of 173 H5N1 NA gene sequences we had identified a 50-base highly conserved region in 3'-terminal end of the NA gene. RESULTS: We extend the graphical and numerical analyses to a larger number of H5N1 NA sequences (514) and H1N1 swine flu sequences (425) accessed from GenBank. We use a 2D graphical representation model for the gene sequences and a Graphical Sliding Window Method (GSWM) for protein sequences scanning the sequences as a block of 16 amino acids at a time. Using a protein sequence descriptor defined in our model, the protein sliding scan method allowed us to compare the different strains for block level variability, which showed significant statistical correlation to average solvent accessibility of the residue blocks; single amino acid position variability results in no correlation, indicating the impact of stretch variability in chemical environment. Close to the C-terminal end the GSWM showed less descriptor-variability with increased average solvent accessibility (ASA) that is also supported by conserved predicted secondary structure of 3' terminal RNA and visual evidence from 3D crystallographic structure. CONCLUSION: The identified terminal segment, strongly conserved in both RNA and protein sequences, is especially significant as it is surface exposed and structural chemistry reveals the probable role of this stretch in tetrameric stabilization. It could also participate in other biological processes associated with conserved surface residues. A RNA double hairpin secondary structure found in this segment in a majority of the H5N1 strains also supports this observation. In this paper we propose this conserved region as a probable site for designing inhibitors for broad-spectrum pandemic control of flu viruses with similar NA structure.",2010 Feb 22,"['Ghosh, Ambarnil', 'Nandy, Ashesh', 'Nandy, Papiya']",BMC Struct Biol,,,True
89d0e2ff08a2a140032fffa032af6dffb1ddae07,PMC,Predicting Drug-Target Interaction Networks Based on Functional Groups and Biological Features,http://dx.doi.org/10.1371/journal.pone.0009603,PMC2836373,20300175,CC BY,"BACKGROUND: Study of drug-target interaction networks is an important topic for drug development. It is both time-consuming and costly to determine compound-protein interactions or potential drug-target interactions by experiments alone. As a complement, the in silico prediction methods can provide us with very useful information in a timely manner. METHODS/PRINCIPAL FINDINGS: To realize this, drug compounds are encoded with functional groups and proteins encoded by biological features including biochemical and physicochemical properties. The optimal feature selection procedures are adopted by means of the mRMR (Maximum Relevance Minimum Redundancy) method. Instead of classifying the proteins as a whole family, target proteins are divided into four groups: enzymes, ion channels, G-protein- coupled receptors and nuclear receptors. Thus, four independent predictors are established using the Nearest Neighbor algorithm as their operation engine, with each to predict the interactions between drugs and one of the four protein groups. As a result, the overall success rates by the jackknife cross-validation tests achieved with the four predictors are 85.48%, 80.78%, 78.49%, and 85.66%, respectively. CONCLUSION/SIGNIFICANCE: Our results indicate that the network prediction system thus established is quite promising and encouraging.",2010 Mar 11,"['He, Zhisong', 'Zhang, Jian', 'Shi, Xiao-He', 'Hu, Le-Le', 'Kong, Xiangyin', 'Cai, Yu-Dong', 'Chou, Kuo-Chen']",PLoS One,,,True
345180770287ab9188e2dcfa2fd2ba0cd58214bb,PMC,Associations between attributes of live poultry trade and HPAI H5N1 outbreaks: a descriptive and network analysis study in northern Vietnam,http://dx.doi.org/10.1186/1746-6148-6-10,PMC2837645,20175881,CC BY,"BACKGROUND: The structure of contact between individuals plays an important role in the incursion and spread of contagious diseases in both human and animal populations. In the case of avian influenza, the movement of live birds is a well known risk factor for the geographic dissemination of the virus among poultry flocks. Live bird markets (LBM's) contribute to the epidemiology of avian influenza due to their demographic characteristics and the presence of HPAI H5N1 virus lineages. The relationship between poultry producers and live poultry traders (LPT's) that operate in LBM's has not been adequately documented in HPAI H5N1-affected SE Asian countries. The aims of this study were to document and study the flow of live poultry in a poultry trade network in northern Vietnam, and explore its potential role in the risk for HPAI H5N1 during 2003 to 2006. RESULTS: Our results indicate that LPT's trading for less than a year and operating at retail markets are more likely to source poultry from flocks located in communes with a past history of HPAI H5N1 outbreaks during 2003 to 2006 than LPT's trading longer than a year and operating at wholesale markets. The results of the network analysis indicate that LPT's tend to link communes of similar infection status. CONCLUSIONS: Our study provides evidence which can be used for informing policies aimed at encouraging more biosecure practices of LPT's operating at authorised LBM's. The results suggest that LPT's play a role in HPAI H5N1 transmission and may contribute to perpetuating HPAI H5N1 virus circulation amongst certain groups of communes. The impact of current disease prevention and control interventions could be enhanced by disseminating information about outbreak risk and the implementation of a formal data recording scheme at LBM's for all incoming and outgoing LPT's.",2010 Feb 22,"['Soares Magalhães, Ricardo J', 'Ortiz-Pelaez, Angel', 'Thi, Kim Lan Lai', 'Dinh, Quoc Hoang', 'Otte, Joachim', 'Pfeiffer, Dirk U']",BMC Vet Res,,,True
73d7ae5e79b6ba07548cf38ddcaa2979bee6916b,PMC,Origin of measles virus: divergence from rinderpest virus between the 11(th )and 12(th )centuries,http://dx.doi.org/10.1186/1743-422X-7-52,PMC2838858,20202190,CC BY,"Measles, caused by measles virus (MeV), is a common infection in children. MeV is a member of the genus Morbillivirus and is most closely related to rinderpest virus (RPV), which is a pathogen of cattle. MeV is thought to have evolved in an environment where cattle and humans lived in close proximity. Understanding the evolutionary history of MeV could answer questions related to divergence times of MeV and RPV. We investigated divergence times using relaxed clock Bayesian phylogenetics. Our estimates reveal that MeV had an evolutionary rate of 6.0 - 6.5 × 10(-4 )substitutions/site/year. It was concluded that the divergence time of the most recent common ancestor of current MeV was the early 20(th )century. And, divergence between MeV and RPV occurred around the 11(th )to 12(th )centuries. The result was unexpected because emergence of MeV was previously considered to have occurred in the prehistoric age. MeV may have originated from virus of non-human species and caused emerging infectious diseases around the 11(th )to 12(th )centuries. In such cases, investigating measles would give important information about the course of emerging infectious diseases.",2010 Mar 4,"['Furuse, Yuki', 'Suzuki, Akira', 'Oshitani, Hitoshi']",Virol J,,,True
31042ccf8374ad96d39d8156d9e2ced042734ba9,PMC,High-throughput detection of mutations responsible for childhood hearing loss using resequencing microarrays,http://dx.doi.org/10.1186/1472-6750-10-10,PMC2841091,20146813,CC BY,"BACKGROUND: Despite current knowledge of mutations in 45 genes that can cause nonsyndromic sensorineural hearing loss (SNHL), no unified clinical test has been developed that can comprehensively detect mutations in multiple genes. We therefore designed Affymetrix resequencing microarrays capable of resequencing 13 genes mutated in SNHL (GJB2, GJB6, CDH23, KCNE1, KCNQ1, MYO7A, OTOF, PDS, MYO6, SLC26A5, TMIE, TMPRSS3, USH1C). We present results from hearing loss arrays developed in two different research facilities and highlight some of the approaches we adopted to enhance the applicability of resequencing arrays in a clinical setting. RESULTS: We leveraged sequence and intensity pattern features responsible for diminished coverage and accuracy and developed a novel algorithm, sPROFILER, which resolved >80% of no-calls from GSEQ and allowed 99.6% (range: 99.2-99.8%) of sequence to be called, while maintaining overall accuracy at >99.8% based upon dideoxy sequencing comparison. CONCLUSIONS: Together, these findings provide insight into critical issues for disease-centered resequencing protocols suitable for clinical application and support the use of array-based resequencing technology as a valuable molecular diagnostic tool for pediatric SNHL and other genetic diseases with substantial genetic heterogeneity.",2010 Feb 10,"['Kothiyal, Prachi', 'Cox, Stephanie', 'Ebert, Jonathan', 'Husami, Ammar', 'Kenna, Margaret A', 'Greinwald, John H', 'Aronow, Bruce J', 'Rehm, Heidi L']",BMC Biotechnol,,,True
4faf1ac964c605b384dda60bc37df300766401b9,PMC,NSs Encoded by Groundnut Bud Necrosis Virus Is a Bifunctional Enzyme,http://dx.doi.org/10.1371/journal.pone.0009757,PMC2841200,20305786,CC BY,"Groundnut bud necrosis virus (GBNV), a member of genus Tospovirus in the family Bunyaviridae, infects a large number of leguminosae and solanaceae plants in India. With a view to elucidate the function of nonstructural protein, NSs encoded by the small RNA genome (S RNA), the NSs protein of GBNV- tomato (Karnataka) [1] was over-expressed in E. coli and purified by Ni-NTA chromatography. The purified rNSs protein exhibited an RNA stimulated NTPase activity. Further, this activity was metal ion dependent and was inhibited by adenosine 5′ (β, γ imido) triphosphate, an ATP analog. The rNSs could also hydrolyze dATP. Interestingly, in addition to the NTPase and dATPase activities, the rNSs exhibited ATP independent 5′ RNA/DNA phosphatase activity that was completely inhibited by AMP. The 5′ α phosphate could be removed from ssDNA, ssRNA, dsDNA and dsRNA thus confirming that rNSs has a novel 5′ α phosphatase activity. K189A mutation in the Walker motif A (GxxxxGKT) resulted in complete loss of ATPase activity, but the 5′ phosphatase activity was unaffected. On the other hand, D159A mutation in the Walker motif B (DExx) resulted in partial loss of both the activities. These results demonstrate for the first time that NSs is a bifunctional enzyme, which could participate in viral movement, replication or in suppression of the host defense mechanism.",2010 Mar 18,"['Lokesh, Bhushan', 'Rashmi, Panigrahi R.', 'Amruta, Bhat S.', 'Srisathiyanarayanan, Dharmaiah', 'Murthy, Mathur R. N.', 'Savithri, Handanahal S.']",PLoS One,,,True
05a94d5f5083ff58320c659cd519536d3e6aa4a3,PMC,A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry,http://dx.doi.org/10.1371/journal.ppat.1000808,PMC2841620,20333243,CC BY,"Viruses use cellular machinery to enter and infect cells. In this study we address the cell entry mechanisms of nonenveloped adenoviruses (Ads). We show that protein VI, an internal capsid protein, is rapidly exposed after cell surface attachment and internalization and remains partially associated with the capsid during intracellular transport. We found that a PPxY motif within protein VI recruits Nedd4 E3 ubiquitin ligases to bind and ubiquitylate protein VI. We further show that this PPxY motif is involved in rapid, microtubule-dependent intracellular movement of protein VI. Ads with a mutated PPxY motif can efficiently escape endosomes but are defective in microtubule-dependent trafficking toward the nucleus. Likewise, depletion of Nedd4 ligases attenuates nuclear accumulation of incoming Ad particles and infection. Our data provide the first evidence that virus-encoded PPxY motifs are required during virus entry, which may be of significance for several other pathogens.",2010 Mar 19,"['Wodrich, Harald', 'Henaff, Daniel', 'Jammart, Baptist', 'Segura-Morales, Carolina', 'Seelmeir, Sigrid', 'Coux, Olivier', 'Ruzsics, Zsolt', 'Wiethoff, Christopher M.', 'Kremer, Eric J.']",PLoS Pathog,,,True
73939a4a3eff4347a97d4dbe05c46a3a1fc08a82,PMC,University life and pandemic influenza: Attitudes and intended behaviour of staff and students towards pandemic (H1N1) 2009,http://dx.doi.org/10.1186/1471-2458-10-130,PMC2841672,20226093,CC BY,"BACKGROUND: In a pandemic young adults are more likely to be infected, increasing the potential for Universities to be explosive disease outbreak centres. Outbreak management is essential to reduce the impact in both the institution and the surrounding community. Through the use of an online survey, we aimed to measure the perceptions and responses of staff and students towards pandemic (H1N1) 2009 at a major university in Sydney, Australia. METHODS: The survey was available online from 29 June to 30 September 2009. The sample included academic staff, general staff and students of the University. RESULTS: A total of 2882 surveys were completed. Nearly all respondents (99.6%, 2870/2882) were aware of the Australian pandemic situation and 64.2% (1851/2882) reported either ""no anxiety"" or ""disinterest."" Asian-born respondents were significantly (p < 0.001) more likely to believe that the pandemic was serious compared to respondents from other regions. 75.9% (2188/2882) of respondents had not made any lifestyle changes as a result of the pandemic. Most respondents had not adopted any specific behaviour change, and only 20.8% (600/2882) had adopted the simplest health behaviour, i.e. hand hygiene. Adoption of a specific behaviour change was linked to anxiety and Asian origin. Students were more likely to attend the university if unwell compared with staff members. Positive responses from students strongly indicate the potential for expanding online teaching and learning resources for continuing education in disaster settings. Willingness to receive the pandemic vaccine was associated with seasonal influenza vaccination uptake over the previous 3 years. CONCLUSIONS: Responses to a pandemic are subject to change in its pre-, early and mid-outbreak stages. Lessons for these institutions in preparation for a second wave and future disease outbreaks include the need to promote positive public health behaviours amongst young people and students.",2010 Mar 14,"['Van, Debbie', 'McLaws, Mary-Louise', 'Crimmins, Jacinta', 'MacIntyre, C Raina', 'Seale, Holly']",BMC Public Health,,,True
91b6e6a867abca446f467eeadcdbbfda198af6a1,PMC,Plug-and-play inference for disease dynamics: measles in large and small populations as a case study,http://dx.doi.org/10.1098/rsif.2009.0151,PMC2842609,19535416,CC BY,"Statistical inference for mechanistic models of partially observed dynamic systems is an active area of research. Most existing inference methods place substantial restrictions upon the form of models that can be fitted and hence upon the nature of the scientific hypotheses that can be entertained and the data that can be used to evaluate them. In contrast, the so-called plug-and-play methods require only simulations from a model and are thus free of such restrictions. We show the utility of the plug-and-play approach in the context of an investigation of measles transmission dynamics. Our novel methodology enables us to ask and answer questions that previous analyses have been unable to address. Specifically, we demonstrate that plug-and-play methods permit the development of a modelling and inference framework applicable to data from both large and small populations. We thereby obtain novel insights into the nature of heterogeneity in mixing and comment on the importance of including extra-demographic stochasticity as a means of dealing with environmental stochasticity and model misspecification. Our approach is readily applicable to many other epidemiological and ecological systems.",2010 Feb 6,"['He, Daihai', 'Ionides, Edward L.', 'King, Aaron A.']",J R Soc Interface,,,True
f2ab1be1bbd80c0f102714fdc90597af2739442c,PMC,"Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret",http://dx.doi.org/10.1371/journal.pone.0009812,PMC2843722,20352112,CC0,"Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge.",2010 Mar 23,"['Rao, Srinivas S.', 'Kong, Wing-Pui', 'Wei, Chih-Jen', 'Van Hoeven, Neal', 'Gorres, J. Patrick', 'Nason, Martha', 'Andersen, Hanne', 'Tumpey, Terrence M.', 'Nabel, Gary J.']",PLoS One,,,True
94cd1610fd21b8fc289d65a96973216217a955dd,PMC,"Awareness, attitudes, and practices related to the swine influenza pandemic among the Saudi public",http://dx.doi.org/10.1186/1471-2334-10-42,PMC2844401,20187976,CC BY,"BACKGROUND: During an infectious disease outbreak, it is critical to learn as much as possible about the concerns, knowledge, attitudes, and behavior of the public. Such information can be crucial to the improvement of communication efforts by public health officials and clinicians. The aim of this study was to identify awareness, attitudes, and practices related to influenza A (H1N1) among the Saudi public. METHODS: A cross-sectional study of 1,548 adult subjects recruited from various shopping malls in Riyadh and Jeddah was conducted. All of the subjects were interviewed using a questionnaire that tested their knowledge, attitudes, and use of precautionary measures in relation to the H1N1 influenza pandemic. RESULTS: More than half (54.3%, 840/1548) of the participants showed high concern, 43.7%(677/1548) showed a low level of knowledge, and 60.8%(941/1548) had taken minimal or no precautionary measures. After adjusting for other variables, education level was the only significant predictor of the level of concern (p < 0.001), while greater precautionary measures were taken by participants who were male (p < 0.001), older (p = 0.047), better educated (p = 0.04), and more knowledgeable (p < 0.001). More than one-third (38.3%) of participants were not convinced that the MOH reports about the disease were true, and only 16.1% of the participants reported receiving information from health providers. CONCLUSIONS: High concern did not translate into a higher compliance with precautionary recommendations, possibly due to the low level of knowledge about the disease among the public. Frequent communication between physicians and the public is recommended to help dispel myths about the disease and to spread better information about the role that the public can play in limiting the spread of the disease.",2010 Feb 28,"['Balkhy, Hanan H', 'Abolfotouh, Mostafa A', 'Al-Hathlool, Rawabi H', 'Al-Jumah, Mohammad A']",BMC Infect Dis,,,True
bf3ec9cb72885b43173311a92e237c5417a53883,PMC,The Impact of Contact Tracing in Clustered Populations,http://dx.doi.org/10.1371/journal.pcbi.1000721,PMC2845652,20361048,CC BY,"The tracing of potentially infectious contacts has become an important part of the control strategy for many infectious diseases, from early cases of novel infections to endemic sexually transmitted infections. Here, we make use of mathematical models to consider the case of partner notification for sexually transmitted infection, however these models are sufficiently simple to allow more general conclusions to be drawn. We show that, when contact network structure is considered in addition to contact tracing, standard “mass action” models are generally inadequate. To consider the impact of mutual contacts (specifically clustering) we develop an improvement to existing pairwise network models, which we use to demonstrate that ceteris paribus, clustering improves the efficacy of contact tracing for a large region of parameter space. This result is sometimes reversed, however, for the case of highly effective contact tracing. We also develop stochastic simulations for comparison, using simple re-wiring methods that allow the generation of appropriate comparator networks. In this way we contribute to the general theory of network-based interventions against infectious disease.",2010 Mar 26,"['House, Thomas', 'Keeling, Matt J.']",PLoS Comput Biol,,,True
de33cc55be6bb27a8f52e33fe21836c670252e28,PMC,Serological Profiling of a Candida albicans Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia,http://dx.doi.org/10.1371/journal.ppat.1000827,PMC2845659,20361054,CC0,"Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.",2010 Mar 26,"['Mochon, A. Brian', 'Ye, Jin', 'Kayala, Matthew A.', 'Wingard, John R.', 'Clancy, Cornelius J.', 'Nguyen, M. Hong', 'Felgner, Philip', 'Baldi, Pierre', 'Liu, Haoping']",PLoS Pathog,,,True
808bc72c8ec0d2cb6bc74492c1155f0528057417,PMC,Serological Profiling of a Candida albicans Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia,http://dx.doi.org/10.1371/journal.ppat.1000827,PMC2845659,20361054,CC0,"Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.",2010 Mar 26,"['Mochon, A. Brian', 'Ye, Jin', 'Kayala, Matthew A.', 'Wingard, John R.', 'Clancy, Cornelius J.', 'Nguyen, M. Hong', 'Felgner, Philip', 'Baldi, Pierre', 'Liu, Haoping']",PLoS Pathog,,,False
28ac05c52a6ce75d7a7b9ae00a335dbb7c1d4883,PMC,Serological Profiling of a Candida albicans Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia,http://dx.doi.org/10.1371/journal.ppat.1000827,PMC2845659,20361054,CC0,"Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.",2010 Mar 26,"['Mochon, A. Brian', 'Ye, Jin', 'Kayala, Matthew A.', 'Wingard, John R.', 'Clancy, Cornelius J.', 'Nguyen, M. Hong', 'Felgner, Philip', 'Baldi, Pierre', 'Liu, Haoping']",PLoS Pathog,,,False
f7c515de412154ba8b4e23343ce1d03ec897cc77,PMC,Serological Profiling of a Candida albicans Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia,http://dx.doi.org/10.1371/journal.ppat.1000827,PMC2845659,20361054,CC0,"Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.",2010 Mar 26,"['Mochon, A. Brian', 'Ye, Jin', 'Kayala, Matthew A.', 'Wingard, John R.', 'Clancy, Cornelius J.', 'Nguyen, M. Hong', 'Felgner, Philip', 'Baldi, Pierre', 'Liu, Haoping']",PLoS Pathog,,,False
e68377f2ea4468c026ad36b35be9f08f48c9a24b,PMC,Serological Profiling of a Candida albicans Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia,http://dx.doi.org/10.1371/journal.ppat.1000827,PMC2845659,20361054,CC0,"Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.",2010 Mar 26,"['Mochon, A. Brian', 'Ye, Jin', 'Kayala, Matthew A.', 'Wingard, John R.', 'Clancy, Cornelius J.', 'Nguyen, M. Hong', 'Felgner, Philip', 'Baldi, Pierre', 'Liu, Haoping']",PLoS Pathog,,,False
2a71668dd2b73cbbeb5005a2905688ed276603a9,PMC,Searching for the elusive typhoid diagnostic,http://dx.doi.org/10.1186/1471-2334-10-45,PMC2846943,20205702,CC BY,"Typhoid (enteric) fever is still a common disease in many developing countries but current diagnostic tests are inadequate. Studies on pathogenesis and genomics have provided new insight into the organisms that cause enteric fever. Better understanding of the microorganisms explains, in part, why our current typhoid methodologies are limited in their diagnostic information and why developing new strategies may be a considerable challenge. Here we discuss the current position of typhoid diagnostics, highlight the need for technological improvements and suggest potential ways of advancing this area.",2010 Mar 5,"['Baker, Stephen', 'Favorov, Michael', 'Dougan, Gordon']",BMC Infect Dis,,,True
7e9494784505c616553ef19805fb9dd82c89dea9,PMC,"A comparative epidemiologic analysis of SARS in Hong Kong, Beijing and Taiwan",http://dx.doi.org/10.1186/1471-2334-10-50,PMC2846944,20205928,CC BY,"BACKGROUND: The 2002-2003 Severe Acute Respiratory Syndrome (SARS) outbreak infected 8,422 individuals leading to 916 deaths around the world. However, there have been few epidemiological studies of SARS comparing epidemiologic features across regions. The aim of this study is to identify similarities and differences in SARS epidemiology in three populations with similar host and viral genotype. METHODS: We present a comparative epidemiologic analysis of SARS, based on an integrated dataset with 3,336 SARS patients from Hong Kong, Beijing and Taiwan, epidemiological and clinical characteristics such as incubation, onset-to-admission, onset-to-discharge and onset-to-death periods, case fatality ratios (CFRs) and presenting symptoms are described and compared between regions. We further explored the influence of demographic and clinical variables on the apparently large differences in CFRs between the three regions. RESULTS: All three regions showed similar incubation periods and progressive shortening of the onset-to-admission interval through the epidemic. Adjusted for sex, health care worker status and nosocomial setting, older age was associated with a higher fatality, with adjusted odds ratio (AOR): 2.10 (95% confidence interval: 1.45, 3.04) for those aged 51-60; AOR: 4.57 (95% confidence interval: 3.32, 7.30) for those aged above 60 compared to those aged 41-50 years. Presence of pre-existing comorbid conditions was also associated with greater mortality (AOR: 1.74; 95% confidence interval: 1.36, 2.21). CONCLUSION: The large discrepancy in crude fatality ratios across the three regions can only be partly explained by epidemiological and clinical heterogeneities. Our findings underline the importance of a common data collection platform, especially in an emerging epidemic, in order to identify and explain consistencies and differences in the eventual clinical and public health outcomes of infectious disease outbreaks, which is becoming increasingly important in our highly interconnected world.",2010 Mar 6,"['Lau, Eric HY', 'Hsiung, C Agnes', 'Cowling, Benjamin J', 'Chen, Chang-Hsun', 'Ho, Lai-Ming', 'Tsang, Thomas', 'Chang, Chiu-Wen', 'Donnelly, Christl A', 'Leung, Gabriel M']",BMC Infect Dis,,,True
2a8a6ddd84f0c80ce33fed8960c3201c08e56854,PMC,Nucleolar localization of influenza A NS1: striking differences between mammalian and avian cells,http://dx.doi.org/10.1186/1743-422X-7-63,PMC2847567,20236536,CC BY,"In mammalian cells, nucleolar localization of influenza A NS1 requires the presence of a C-terminal nucleolar localization signal. This nucleolar localization signal is present only in certain strains of influenza A viruses. Therefore, only certain NS1 accumulate in the nucleolus of mammalian cells. In contrast, we show that all NS1 tested in this study accumulated in the nucleolus of avian cells even in the absence of the above described C-terminal nucleolar localization signal. Thus, nucleolar localization of NS1 in avian cells appears to rely on a different nucleolar localization signal that is more conserved among influenza virus strains.",2010 Mar 17,"['Volmer, Romain', 'Mazel-Sanchez, Beryl', 'Volmer, Christelle', 'Soubies, Sébastien M', 'Guérin, Jean-Luc']",Virol J,,,True
846f108dcf44ed854491112e1de0c86b5193cb86,PMC,Self-reported anticipated compliance with physician advice to stay home during pandemic (H1N1) 2009: Results from the 2009 Queensland Social Survey,http://dx.doi.org/10.1186/1471-2458-10-138,PMC2847980,20233450,CC BY,"BACKGROUND: One strategy available to public health officials during a pandemic is physician recommendations for isolation of infected individuals. This study was undertaken during the height of the Australian pandemic (H1N1) 2009 outbreak to measure self-reported willingness to comply with physician recommendations to stay home for seven days, and to compare responses for the current strain of pandemic influenza, avian influenza, seasonal influenza, and the common cold. METHODS: Data were collected as part of the Queensland Social Survey (QSS) 2009, which consisted of a standardized introduction, 37 demographic questions, and research questions incorporated through a cost-sharing arrangement. Four questions related to respondents' anticipated compliance with a physician's advice to stay home if they had a common cold, seasonal influenza, pandemic (H1N1) 2009 influenza or avian influenza were incorporated into QSS 2009, with responses recorded using a balanced Likert scale ranging from ""very unlikely"" to ""very likely."" Discordance between responses for different diseases was analysed using McNemar's test. Associations between demographic variables and anticipated compliance were analysed using Pearson's chi-square or chi-square for linear-by-linear association, and confirmed using multivariate logistic regression; p < 0.05 was used to establish statistical significance. RESULTS: Self-reported anticipated compliance increased from 59.9% for the common cold to 71.3% for seasonal influenza (p < .001), and to 95.0% for pandemic (H1N1) 2009 influenza and 94.7% for avian influenza (p < 0.001 for both versus seasonal influenza). Anticipated compliance did not differ for pandemic (H1N1) 2009 and avian influenza (p = 0.815). Age and sex were both associated with anticipated compliance in the setting of seasonal influenza and the common cold. Notably, 27.1% of health and community service workers would not comply with physician advice to stay home for seasonal influenza. CONCLUSIONS: Ninety-five percent of people report they would comply with a physicians' advice to stay home for seven days if they are diagnosed with pandemic (H1N1) 2009 or avian influenza, but only 71% can be expected to comply in the setting of seasonal influenza and fewer still can be expected to comply if they are diagnosed with a common cold. Sub-populations that might be worthwhile targets for public health messages aimed at increasing the rate of self-imposed isolation for seasonal influenza include males, younger people, and healthcare workers.",2010 Mar 16,"['Brown, Lawrence H', 'Aitken, Peter', 'Leggat, Peter A', 'Speare, Richard']",BMC Public Health,,,True
50aa060bb87a548227b5b972c63920faef016f05,PMC,"Healthcare workers and health care-associated infections: knowledge, attitudes, and behavior in emergency departments in Italy",http://dx.doi.org/10.1186/1471-2334-10-35,PMC2848042,20178573,CC BY,"BACKGROUND: This survey assessed knowledge, attitudes, and compliance regarding standard precautions about health care-associated infections (HAIs) and the associated determinants among healthcare workers (HCWs) in emergency departments in Italy. METHODS: An anonymous questionnaire, self-administered by all HCWs in eight randomly selected non-academic acute general public hospitals, comprised questions on demographic and occupational characteristics; knowledge about the risks of acquiring and/or transmitting HAIs from/to a patient and standard precautions; attitudes toward guidelines and risk perceived of acquiring a HAI; practice of standard precautions; and sources of information. RESULTS: HCWs who know the risk of acquiring Hepatitis C (HCV) and Human Immunodeficiency Virus (HIV) from a patient were in practice from less years, worked fewer hours per week, knew that a HCW can transmit HCV and HIV to a patient, knew that HCV and HIV infections can be serious, and have received information from educational courses and scientific journals. Those who know that gloves, mask, protective eyewear, and hands hygiene after removing gloves are control measures were nurses, provided care to fewer patients, knew that HCWs' hands are vehicle for transmission of nosocomial pathogens, did not know that a HCW can transmit HCV and HIV to a patient, and have received information from educational courses and scientific journals. Being a nurse, knowing that HCWs' hands are vehicle for transmission of nosocomial pathogens, obtaining information from educational courses and scientific journals, and needing information were associated with a higher perceived risk of acquiring a HAI. HCWs who often or always used gloves and performed hands hygiene measures after removing gloves were nurses, provided care to fewer patients, and knew that hands hygiene after removing gloves was a control measure. CONCLUSIONS: HCWs have high knowledge, positive attitudes, but low compliance concerning standard precautions. Nurses had higher knowledge, perceived risk, and appropriate HAIs' control measures than physicians and HCWs answered correctly and used appropriately control measures if have received information from educational courses and scientific journals.",2010 Feb 23,"['Parmeggiani, Cristiana', 'Abbate, Rossella', 'Marinelli, Paolo', 'Angelillo, Italo F']",BMC Infect Dis,,,True
140cdf5d99f486ccd0346d07cad3fa66b2567c42,PMC,Rapid Accumulation of Virulent Rift Valley Fever Virus in Mice from an Attenuated Virus Carrying a Single Nucleotide Substitution in the M RNA,http://dx.doi.org/10.1371/journal.pone.0009986,PMC2848673,20376320,CC BY,"BACKGROUND: Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, while in livestock it causes fever and high abortion rates. METHODOLOGY/PRINCIPAL FINDINGS: Sequence analysis showed that a wild-type RVFV ZH501 preparation consisted of two major viral subpopulations, with a single nucleotide heterogeneity at nucleotide 847 of M segment (M847); one had a G residue at M847 encoding glycine in a major viral envelope Gn protein, while the other carried A residue encoding glutamic acid at the corresponding site. Two ZH501-derived viruses, rZH501-M847-G and rZH501-M847-A, carried identical genomic sequences, except that the former and the latter had G and A, respectively, at M847 were recovered by using a reverse genetics system. Intraperitoneal inoculation of rZH501-M847-A into mice caused a rapid and efficient viral accumulation in the sera, livers, spleens, kidneys and brains, and killed most of the mice within 8 days, whereas rZH501-M847-G caused low viremia titers, did not replicate as efficiently as did rZH501-M847-A in these organs, and had attenuated virulence to mice. Remarkably, as early as 2 days postinfection with rZH501-M847-G, the viruses carrying A at M847 emerged and became the major virus population thereafter, while replicating viruses retained the input A residue at M847 in rZH501-M847-A-infected mice. CONCLUSIONS/SIGNIFICANCE: These data demonstrated that the single nucleotide substitution in the Gn protein substantially affected the RVFV mouse virulence and that a virus population carrying the virulent viral genotype quickly emerged and became the major viral population within a few days in mice that were inoculated with the attenuated virus.",2010 Apr 1,"['Morrill, John C.', 'Ikegami, Tetsuro', 'Yoshikawa-Iwata, Naoko', 'Lokugamage, Nandadeva', 'Won, Sungyong', 'Terasaki, Kaori', 'Zamoto-Niikura, Aya', 'Peters, C. J.', 'Makino, Shinji']",PLoS One,,,True
5b454b34b6611cd015799280a78b9fed001068cb,PMC,An optimal control theory approach to non-pharmaceutical interventions,http://dx.doi.org/10.1186/1471-2334-10-32,PMC2850906,20170501,CC BY,"BACKGROUND: Non-pharmaceutical interventions (NPI) are the first line of defense against pandemic influenza. These interventions dampen virus spread by reducing contact between infected and susceptible persons. Because they curtail essential societal activities, they must be applied judiciously. Optimal control theory is an approach for modeling and balancing competing objectives such as epidemic spread and NPI cost. METHODS: We apply optimal control on an epidemiologic compartmental model to develop triggers for NPI implementation. The objective is to minimize expected person-days lost from influenza related deaths and NPI implementations for the model. We perform a multivariate sensitivity analysis based on Latin Hypercube Sampling to study the effects of input parameters on the optimal control policy. Additional studies investigated the effects of departures from the modeling assumptions, including exponential terminal time and linear NPI implementation cost. RESULTS: An optimal policy is derived for the control model using a linear NPI implementation cost. Linear cost leads to a ""bang-bang"" policy in which NPIs are applied at maximum strength when certain state criteria are met. Multivariate sensitivity analyses are presented which indicate that NPI cost, death rate, and recovery rate are influential in determining the policy structure. Further death rate, basic reproductive number and recovery rate are the most influential in determining the expected cumulative death. When applying the NPI policy, the cumulative deaths under exponential and gamma terminal times are close, which implies that the outcome of applying the ""bang-bang"" policy is insensitive to the exponential assumption. Quadratic cost leads to a multi-level policy in which NPIs are applied at varying strength levels, again based on certain state criteria. Results indicate that linear cost leads to more costly implementation resulting in fewer deaths. CONCLUSIONS: The application of optimal control theory can provide valuable insight to developing effective control strategies for pandemic. Our findings highlight the importance of establishing a sensitive and timely surveillance system for pandemic preparedness.",2010 Feb 19,"['Lin, Feng', 'Muthuraman, Kumar', 'Lawley, Mark']",BMC Infect Dis,,,True
476c677579fa461c4fbe5822f1df9a687a6d8928,PMC,Dynamics and Control of Diseases in Networks with Community Structure,http://dx.doi.org/10.1371/journal.pcbi.1000736,PMC2851561,20386735,CC BY,"The dynamics of infectious diseases spread via direct person-to-person transmission (such as influenza, smallpox, HIV/AIDS, etc.) depends on the underlying host contact network. Human contact networks exhibit strong community structure. Understanding how such community structure affects epidemics may provide insights for preventing the spread of disease between communities by changing the structure of the contact network through pharmaceutical or non-pharmaceutical interventions. We use empirical and simulated networks to investigate the spread of disease in networks with community structure. We find that community structure has a major impact on disease dynamics, and we show that in networks with strong community structure, immunization interventions targeted at individuals bridging communities are more effective than those simply targeting highly connected individuals. Because the structure of relevant contact networks is generally not known, and vaccine supply is often limited, there is great need for efficient vaccination algorithms that do not require full knowledge of the network. We developed an algorithm that acts only on locally available network information and is able to quickly identify targets for successful immunization intervention. The algorithm generally outperforms existing algorithms when vaccine supply is limited, particularly in networks with strong community structure. Understanding the spread of infectious diseases and designing optimal control strategies is a major goal of public health. Social networks show marked patterns of community structure, and our results, based on empirical and simulated data, demonstrate that community structure strongly affects disease dynamics. These results have implications for the design of control strategies.",2010 Apr 8,"['Salathé, Marcel', 'Jones, James H.']",PLoS Comput Biol,,,True
68ac410cd36c5699f58d2b76b0eeb84956573f77,PMC,"SARS-CoV Pathogenesis Is Regulated by a STAT1 Dependent but a Type I, II and III Interferon Receptor Independent Mechanism",http://dx.doi.org/10.1371/journal.ppat.1000849,PMC2851658,20386712,CC0,"Severe acute respiratory syndrome coronavirus (SARS-CoV) infection often caused severe end stage lung disease and organizing phase diffuse alveolar damage, especially in the elderly. The virus-host interactions that governed development of these acute end stage lung diseases and death are unknown. To address this question, we evaluated the role of innate immune signaling in protection from human (Urbani) and a recombinant mouse adapted SARS-CoV, designated rMA15. In contrast to most models of viral pathogenesis, infection of type I, type II or type III interferon knockout mice (129 background) with either Urbani or MA15 viruses resulted in clinical disease outcomes, including transient weight loss, denuding bronchiolitis and alveolar inflammation and recovery, identical to that seen in infection of wildtype mice. This suggests that type I, II and III interferon signaling play minor roles in regulating SARS pathogenesis in mouse models. In contrast, infection of STAT1−/− mice resulted in severe disease, high virus titer, extensive pulmonary lesions and 100% mortality by day 9 and 30 post-infection with rMA15 or Urbani viruses, respectively. Non-lethal in BALB/c mice, Urbani SARS-CoV infection in STAT1−/− mice caused disseminated infection involving the liver, spleen and other tissues after day 9. These findings demonstrated that SARS-CoV pathogenesis is regulated by a STAT1 dependent but type I, II and III interferon receptor independent, mechanism. In contrast to a well documented role in innate immunity, we propose that STAT1 also protects mice via its role as an antagonist of unrestrained cell proliferation.",2010 Apr 8,"['Frieman, Matthew B.', 'Chen, Jun', 'Morrison, Thomas E.', 'Whitmore, Alan', 'Funkhouser, William', 'Ward, Jerrold M.', 'Lamirande, Elaine W.', 'Roberts, Anjeanette', 'Heise, Mark', 'Subbarao, Kanta', 'Baric, Ralph S.']",PLoS Pathog,,,True
8d882efc1f6cf141ce6b4283acd7f87b1b280313,PMC,Computer-assisted resilience training to prepare healthcare workers for pandemic influenza: a randomized trial of the optimal dose of training,http://dx.doi.org/10.1186/1472-6963-10-72,PMC2851711,20307302,CC BY,"BACKGROUND: Working in a hospital during an extraordinary infectious disease outbreak can cause significant stress and contribute to healthcare workers choosing to reduce patient contact. Psychological training of healthcare workers prior to an influenza pandemic may reduce stress-related absenteeism, however, established training methods that change behavior and attitudes are too resource-intensive for widespread use. This study tests the feasibility and effectiveness of a less expensive alternative - an interactive, computer-assisted training course designed to build resilience to the stresses of working during a pandemic. METHODS: A ""dose-finding"" study compared pre-post changes in three different durations of training. We measured variables that are likely to mediate stress-responses in a pandemic before and after training: confidence in support and training, pandemic-related self-efficacy, coping style and interpersonal problems. RESULTS: 158 hospital workers took the course and were randomly assigned to the short (7 sessions, median cumulative duration 111 minutes), medium (12 sessions, 158 minutes) or long (17 sessions, 223 minutes) version. Using an intention-to-treat analysis, the course was associated with significant improvements in confidence in support and training, pandemic self-efficacy and interpersonal problems. Participants who under-utilized coping via problem-solving or seeking support or over-utilized escape-avoidance experienced improved coping. Comparison of doses showed improved interpersonal problems in the medium and long course but not in the short course. There was a trend towards higher drop-out rates with longer duration of training. CONCLUSIONS: Computer-assisted resilience training in healthcare workers appears to be of significant benefit and merits further study under pandemic conditions. Comparing three ""doses"" of the course suggested that the medium course was optimal.",2010 Mar 22,"['Maunder, Robert G', 'Lancee, William J', 'Mae, Reet', 'Vincent, Leslie', 'Peladeau, Nathalie', 'Beduz, Mary Agnes', 'Hunter, Jonathan J', 'Leszcz, Molyn']",BMC Health Serv Res,,,True
6204b15a79e3551e09c29cd4865fae0497462ec3,PMC,Generation of Human CEACAM1 Transgenic Mice and Binding of Neisseria Opa Protein to Their Neutrophils,http://dx.doi.org/10.1371/journal.pone.0010067,PMC2852402,20404914,CC BY,"BACKGROUND: Human CEACAM1 is a cell-cell adhesion molecule with multiple functions including insulin clearance in the liver, vasculogenesis in endothelial cells, lumen formation in the mammary gland, and binding of certain human pathogens. PRINCIPAL FINDINGS: Three genomic BAC clones containing the human CEACAM1 gene were microinjected into pronuclei of fertilized FVB mouse oocytes. The embryos were implanted in the oviducts of pseudopregnant females and allowed to develop to term. DNA from newborn mice was evaluated by PCR for the presence of the human CEACAM1 gene. Feces of the PCR positive offspring screened for expression of human CEACAM1. Using this assay, one out of five PCR positive lines was positive for human CEACAM1 expression and showed stable transmission to the F1 generation with the expected transmission frequency (0.5) for heterozygotes. Liver, lung, intestine, kidney, mammary gland, and prostate were strongly positive for the dual expression of both murine and human CEACAM1 and mimic that seen in human tissue. Peripheral blood and bone marrow granulocytes stained strongly for human CEACAM1 and bound Neisseria Opa proteins similar to that in human neutrophils. CONCLUSION: These transgenic animals may serve as a model for the binding of human pathogens to human CEACAM1.",2010 Apr 9,"['Gu, Angel', 'Zhang, Zhifang', 'Zhang, Nan', 'Tsark, Walter', 'Shively, John E.']",PLoS One,,,True
60cd26dae93a4048b5aceb66c68bec325392fdf0,PMC,BioTorrents: A File Sharing Service for Scientific Data,http://dx.doi.org/10.1371/journal.pone.0010071,PMC2854681,20418944,CC BY,"The transfer of scientific data has emerged as a significant challenge, as datasets continue to grow in size and demand for open access sharing increases. Current methods for file transfer do not scale well for large files and can cause long transfer times. In this study we present BioTorrents, a website that allows open access sharing of scientific data and uses the popular BitTorrent peer-to-peer file sharing technology. BioTorrents allows files to be transferred rapidly due to the sharing of bandwidth across multiple institutions and provides more reliable file transfers due to the built-in error checking of the file sharing technology. BioTorrents contains multiple features, including keyword searching, category browsing, RSS feeds, torrent comments, and a discussion forum. BioTorrents is available at http://www.biotorrents.net.",2010 Apr 14,"['Langille, Morgan G. I.', 'Eisen, Jonathan A.']",PLoS One,,,True
5484795b90c22596ead5f0b9ccf08d95a3e6f5c2,PMC,In Vitro Reconstitution of SARS-Coronavirus mRNA Cap Methylation,http://dx.doi.org/10.1371/journal.ppat.1000863,PMC2858705,20421945,CC BY,"SARS-coronavirus (SARS-CoV) genome expression depends on the synthesis of a set of mRNAs, which presumably are capped at their 5′ end and direct the synthesis of all viral proteins in the infected cell. Sixteen viral non-structural proteins (nsp1 to nsp16) constitute an unusually large replicase complex, which includes two methyltransferases putatively involved in viral mRNA cap formation. The S-adenosyl-L-methionine (AdoMet)-dependent (guanine-N7)-methyltransferase (N7-MTase) activity was recently attributed to nsp14, whereas nsp16 has been predicted to be the AdoMet-dependent (nucleoside-2′O)-methyltransferase. Here, we have reconstituted complete SARS-CoV mRNA cap methylation in vitro. We show that mRNA cap methylation requires a third viral protein, nsp10, which acts as an essential trigger to complete RNA cap-1 formation. The obligate sequence of methylation events is initiated by nsp14, which first methylates capped RNA transcripts to generate cap-0 (7Me)GpppA-RNAs. The latter are then selectively 2′O-methylated by the 2′O-MTase nsp16 in complex with its activator nsp10 to give rise to cap-1 (7Me)GpppA(2′OMe)-RNAs. Furthermore, sensitive in vitro inhibition assays of both activities show that aurintricarboxylic acid, active in SARS-CoV infected cells, targets both MTases with IC(50) values in the micromolar range, providing a validated basis for anti-coronavirus drug design.",2010 Apr 22,"['Bouvet, Mickaël', 'Debarnot, Claire', 'Imbert, Isabelle', 'Selisko, Barbara', 'Snijder, Eric J.', 'Canard, Bruno', 'Decroly, Etienne']",PLoS Pathog,,,True
5ca920dabf09c2c2dd2c62f8ef5917e3bd72f087,PMC,The Effect of Vaccination on the Evolution and Population Dynamics of Avian Paramyxovirus-1,http://dx.doi.org/10.1371/journal.ppat.1000872,PMC2858710,20421950,CC BY,"Newcastle Disease Virus (NDV) is a pathogenic strain of avian paramyxovirus (aPMV-1) that is among the most serious of disease threats to the poultry industry worldwide. Viral diversity is high in aPMV-1; eight genotypes are recognized based on phylogenetic reconstruction of gene sequences. Modified live vaccines have been developed to decrease the economic losses caused by this virus. Vaccines derived from avirulent genotype II strains were developed in the 1950s and are in use globally, whereas Australian strains belonging to genotype I were developed as vaccines in the 1970s and are used mainly in Asia. In this study, we evaluated the consequences of attenuated live virus vaccination on the evolution of aPMV-1 genotypes. There was phylogenetic incongruence among trees based on individual genes and complete coding region of 54 full length aPMV-1 genomes, suggesting that recombinant sequences were present in the data set. Subsequently, five recombinant genomes were identified, four of which contained sequences from either genotype I or II. The population history of vaccine-related genotype II strains was distinct from other aPMV-1 genotypes; genotype II emerged in the late 19(th) century and is evolving more slowly than other genotypes, which emerged in the 1960s. Despite vaccination efforts, genotype II viruses have experienced constant population growth to the present. In contrast, other contemporary genotypes showed population declines in the late 1990s. Additionally, genotype I and II viruses, which are circulating in the presence of homotypic vaccine pressure, have unique selection profiles compared to nonvaccine-related strains. Collectively, these data show that vaccination with live attenuated viruses has changed the evolution of aPMV-1 by maintaining a large effective population size of a vaccine-related genotype, allowing for coinfection and recombination of vaccine and wild type strains, and by applying unique selective pressures on viral glycoproteins.",2010 Apr 22,"['Chong, Yee Ling', 'Padhi, Abinash', 'Hudson, Peter J.', 'Poss, Mary']",PLoS Pathog,,,True
f7c3160bef4169d29e2a8bdd79dd6e9056d4774c,PMC,Chikungunya: A Potentially Emerging Epidemic?,http://dx.doi.org/10.1371/journal.pntd.0000623,PMC2860491,20436958,CC BY,"Chikungunya virus is a mosquito-borne emerging pathogen that has a major health impact in humans and causes fever disease, headache, rash, nausea, vomiting, myalgia, and arthralgia. Indigenous to tropical Africa, recent large outbreaks have been reported in parts of South East Asia and several of its neighboring islands in 2005–07 and in Europe in 2007. Furthermore, positive cases have been confirmed in the United States in travelers returning from known outbreak areas. Currently, there is no vaccine or antiviral treatment. With the threat of an emerging global pandemic, the peculiar problems associated with the more immediate and seasonal epidemics warrant the development of an effective vaccine. In this review, we summarize the evidence supporting these concepts.",2010 Apr 27,"['Thiboutot, Michelle M.', 'Kannan, Senthil', 'Kawalekar, Omkar U.', 'Shedlock, Devon J.', 'Khan, Amir S.', 'Sarangan, Gopalsamy', 'Srikanth, Padma', 'Weiner, David B.', 'Muthumani, Karuppiah']",PLoS Negl Trop Dis,,,True
d69356747d4f5a940f9d2ee6e643d895b33f678e,PMC,China's Engagement with Global Health Diplomacy: Was SARS a Watershed?,http://dx.doi.org/10.1371/journal.pmed.1000266,PMC2860492,20436959,CC BY,"As part of the PLoS Medicine series on Global Health Diplomacy, Lai-Han Chan and colleagues provide a case study of China's growing engagement in global health diplomacy following the SARS epidemic.",2010 Apr 27,"['Chan, Lai-Ha', 'Chen, Lucy', 'Xu, Jin']",PLoS Med,,,True
f407fa076e02563e41223d43873e7fd604bdd637,PMC,Chloroquine and Its Derivatives Exacerbate B19V-Associated Anemia by Promoting Viral Replication,http://dx.doi.org/10.1371/journal.pntd.0000669,PMC2860510,20436917,CC BY,"BACKGROUND: An unexpectedly high seroprevalence and pathogenic potential of human parvovirus B19 (B19V) have been observed in certain malaria-endemic countries in parallel with local use of chloroquine (CQ) as first-line treatment for malaria. The aims of this study were to assess the effect of CQ and other common antimalarial drugs on B19V infection in vitro and the possible epidemiological consequences for children from Papua New Guinea (PNG). METHODOLOGY/PRINCIPAL FINDINGS: Viral RNA, DNA and proteins were analyzed in different cell types following infection with B19V in the presence of a range of antimalarial drugs. Relationships between B19V infection status, prior 4-aminoquinoline use and anemia were assessed in 200 PNG children <10 years of age participating in a case-control study of severe infections. In CQ-treated cells, the synthesis of viral RNA, DNA and proteins was significantly higher and occurred earlier than in control cells. CQ facilitates B19V infection by minimizing intracellular degradation of incoming particles. Only amodiaquine amongst other antimalarial drugs had a similar effect. B19V IgM seropositivity was more frequent in 111 children with severe anemia (hemoglobin <50 g/L) than in 89 healthy controls (15.3% vs 3.4%; P = 0.008). In children who were either B19V IgM or PCR positive, 4-aminoquinoline use was associated with a significantly lower admission hemoglobin concentration. CONCLUSIONS/SIGNIFICANCE: Our data strongly suggest that 4-aminoquinoline drugs and their metabolites exacerbate B19V-associated anemia by promoting B19V replication. Consideration should be given for choosing a non-4-aminoquinoline drug to partner artemisinin compounds in combination antimalarial therapy.",2010 Apr 27,"['Bönsch, Claudia', 'Kempf, Christoph', 'Mueller, Ivo', 'Manning, Laurens', 'Laman, Moses', 'Davis, Timothy M. E.', 'Ros, Carlos']",PLoS Negl Trop Dis,,,True
c0f7f46699d0ecf0c7ead699d564d952508e6f81,PMC,Behavioural intentions in response to an influenza pandemic,http://dx.doi.org/10.1186/1471-2458-10-174,PMC2861057,20353568,CC BY,"BACKGROUND: Little is known regarding which behavioural responses can be expected if an influenza pandemic were to occur. METHODS: A survey comprising questions based on risk perception theories, in particular PMT, was conducted with a Dutch sample. RESULTS: Although fear that an influenza pandemic may occur was high, participants do not feel well informed. General practitioners and local health authorities were considered trustworthy sources of information and the information considered most urgent pertained to which protective measures should be taken. Participants reported an intention to comply with recommendations regarding protective measures. However, response and self efficacy were low. Maladaptive behaviours can be expected. Increasing numbers of ill individuals and school closures are also expected to lead to a decreased work force. Participants indicated wanting antiviral drugs even if the supply were to be insufficient. CONCLUSIONS: Messages regarding health protective behaviours from local health authorities should anticipate the balance between overreacting and underreacting. Also, when protective recommendations from health professionals conflict with company policies, it is unclear how employees will react.",2010 Mar 30,"['Kok, Gerjo', 'Jonkers, Ruud', 'Gelissen, Roger', 'Meertens, Ree', 'Schaalma, Herman', 'de Zwart, Onno']",BMC Public Health,,,True
6fb63e6ddb93b95e451c44a18ca67e506e126c3d,PMC,Syndromic Surveillance for Local Outbreaks of Lower-Respiratory Infections: Would It Work?,http://dx.doi.org/10.1371/journal.pone.0010406,PMC2861591,20454449,CC BY,"BACKGROUND: Although syndromic surveillance is increasingly used to detect unusual illness, there is a debate whether it is useful for detecting local outbreaks. We evaluated whether syndromic surveillance detects local outbreaks of lower-respiratory infections (LRIs) without swamping true signals by false alarms. METHODS AND FINDINGS: Using retrospective hospitalization data, we simulated prospective surveillance for LRI-elevations. Between 1999–2006, a total of 290762 LRIs were included by date of hospitalization and patients place of residence (>80% coverage, 16 million population). Two large outbreaks of Legionnaires disease in the Netherlands were used as positive controls to test whether these outbreaks could have been detected as local LRI elevations. We used a space-time permutation scan statistic to detect LRI clusters. We evaluated how many LRI-clusters were detected in 1999–2006 and assessed likely causes for the cluster-signals by looking for significantly higher proportions of specific hospital discharge diagnoses (e.g. Legionnaires disease) and overlap with regional influenza elevations. We also evaluated whether the number of space-time signals can be reduced by restricting the scan statistic in space or time. In 1999–2006 the scan-statistic detected 35 local LRI clusters, representing on average 5 clusters per year. The known Legionnaires' disease outbreaks in 1999 and 2006 were detected as LRI-clusters, since cluster-signals were generated with an increased proportion of Legionnaires disease patients (p:<0.0001). 21 other clusters coincided with local influenza and/or respiratory syncytial virus activity, and 1 cluster appeared to be a data artifact. For 11 clusters no likely cause was defined, some possibly representing as yet undetected LRI-outbreaks. With restrictions on time and spatial windows the scan statistic still detected the Legionnaires' disease outbreaks, without loss of timeliness and with less signals generated in time (up to 42% decline). CONCLUSIONS: To our knowledge this is the first study that systematically evaluates the performance of space-time syndromic surveillance with nationwide high coverage data over a longer period. The results show that syndromic surveillance can detect local LRI-outbreaks in a timely manner, independent of laboratory-based outbreak detection. Furthermore, since comparatively few new clusters per year were observed that would prompt investigation, syndromic hospital-surveillance could be a valuable tool for detection of local LRI-outbreaks.",2010 Apr 29,"['van den Wijngaard, Cees C.', 'van Asten, Liselotte', 'van Pelt, Wilfrid', 'Doornbos, Gerda', 'Nagelkerke, Nico J. D.', 'Donker, Gé A.', 'van der Hoek, Wim', 'Koopmans, Marion P. G.']",PLoS One,,,True
44ab6aecdacb870226ce4ce36606e227f0a6ac00,PMC,Electron Tomography Reveals the Steps in Filovirus Budding,http://dx.doi.org/10.1371/journal.ppat.1000875,PMC2861712,20442788,CC BY,"The filoviruses, Marburg and Ebola, are non-segmented negative-strand RNA viruses causing severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. The sequence of events that leads to release of filovirus particles from cells is poorly understood. Two contrasting mechanisms have been proposed, one proceeding via a “submarine-like” budding with the helical nucleocapsid emerging parallel to the plasma membrane, and the other via perpendicular “rocket-like” protrusion. Here we have infected cells with Marburg virus under BSL-4 containment conditions, and reconstructed the sequence of steps in the budding process in three dimensions using electron tomography of plastic-embedded cells. We find that highly infectious filamentous particles are released at early stages in infection. Budding proceeds via lateral association of intracellular nucleocapsid along its whole length with the plasma membrane, followed by rapid envelopment initiated at one end of the nucleocapsid, leading to a protruding intermediate. Scission results in local membrane instability at the rear of the virus. After prolonged infection, increased vesiculation of the plasma membrane correlates with changes in shape and infectivity of released viruses. Our observations demonstrate a cellular determinant of virus shape. They reconcile the contrasting models of filovirus budding and allow us to describe the sequence of events taking place during budding and release of Marburg virus. We propose that this represents a general sequence of events also followed by other filamentous and rod-shaped viruses.",2010 Apr 29,"['Welsch, Sonja', 'Kolesnikova, Larissa', 'Krähling, Verena', 'Riches, James D.', 'Becker, Stephan', 'Briggs, John A. G.']",PLoS Pathog,,,True
58a9c23ad5702fdc007f682342e3a77fe5516a8f,PMC,HAb18G/CD147 cell-cell contacts confer resistance of a HEK293 subpopulation to anoikis in an E-cadherin-dependent manner,http://dx.doi.org/10.1186/1471-2121-11-27,PMC2864199,20398401,CC BY,"BACKGROUND: Acquisition of resistance to ""anoikis"" facilitates the survival of cells under independent matrix-deficient conditions, such as cells in tumor progression and the production of suspension culture cells for biomedical engineering. There is evidence suggesting that CD147, an adhesion molecule associated with survival of cells in tumor metastasis and cell-cell contacts, plays an important role in resistance to anoikis. However, information regarding the functions of CD147 in mediating cell-cell contacts and anoikis-resistance remains limited and even self-contradictory. RESULTS: An anoikis-resistant clone (HEK293ar), derived from anoikis-sensitive parental Human Embryonic Kidney 293 cells, survived anoikis by the formation of cell-cell contacts. The expression of HAb18G/CD147 (a member of the CD147 family) was upregulated and the protein was located at cell-cell junctions. Upregulation of HAb18G/CD147 in suspended HEK293ar cells suppressed anoikis by mediating the formation of cell-cell adhesions. Anoikis resistance in HEK293ar cells also required E-cadherin-mediated cell-cell contacts. Knock-down of HAb18G/CD147 and E-cadherin inhibited cell-cell contacts formation and increased anoikis sensitivity respectively. When HAb18G/CD147 was downregulated, E-cadherin expression in HEK293ar cells was significantly suppressed; however, knockdown of E-cadherin by E-cadherin siRNA or blocking of E-cadherin binding activity with a specific antibody and EDTA had no significant effect on HAb18G/CD147 expression. Finally, pretreatment with LY294002, a phosphoinositide 3-kinase (PI3K/AKT) inhibitor, disrupted cell-cell contacts and decreased cell number, but this was not the case in cells treated with the extracellular signal-regulated kinase (ERK) inhibitor PD98059. CONCLUSIONS: Our results provide new evidence that HAb18G/CD147-mediated cell-cell contact confers anoikis resistance in an E-cadherin-dependent manner; and cell-cell contact mediated resistance to anoikis implicates PI3K pathway in a highly relevant cell model (HEK293ar). Understanding of the role of HAb18G/CD147 cell-cell contacts in anoikis resistance may help in understanding the survival of cells in anchorage-independent growth, such as cells in tumor metastasis and suspension culture produced for biomedical engineering. Our results also contribute to a better understanding of the biology of HEK293 cell spheroids, a major workhorse for producing human therapeutic agents and viral vaccines.",2010 Apr 17,"['Ma, Xiao-Kui', 'Wang, Li', 'Li, Yu', 'Yang, Xiang-Ming', 'Zhao, Pu', 'HaoTang', 'Zhu, Ping', 'Li, Ling', 'Chen, Zhi-Nan']",BMC Cell Biol,,,True
8e67618920b0226e661e20a2c36b4436857d9590,PMC,Why do I need it? I am not at risk! Public perceptions towards the pandemic (H1N1) 2009 vaccine,http://dx.doi.org/10.1186/1471-2334-10-99,PMC2864274,20403201,CC BY,"BACKGROUND: On the 30th September 2009, the pandemic (H1N1) 2009 influenza vaccine was made available to adults and children aged 10 years and over, in Australia. Acceptance of a novel vaccine is influenced by perceptions of risk including risk of infection, risk of death or severe illness and risk of serious vaccine side-effects. We surveyed a sample of residents from Sydney, Australia to ascertain their risk perception, attitudes towards the pandemic and willingness to accept the pandemic (H1N1) 2009 influenza vaccine. METHODS: We sampled residents using a cross-sectional intercept design during the WHO Phase 6. Members of the public were approached in shopping and pedestrian malls to undertake the survey during September and October 2009. The survey measured perceived risk, seriousness of disease, recent behavioural changes, likely acceptance of the pandemic (H1N1) 2009 vaccine and issues relating to uptake and perceived safety. RESULTS: Of the 627 respondents, the majority felt that they had a ""very low to low"" (332/627, 52.9%) risk of acquiring H1N1. 24.5% (154/627) of respondents believed that the disease would ""very seriously or extremely"" affect their health. Nearly half (305/627, 48.6%) reported that in response to the ""swine flu"" outbreak they had undertaken one or more of the investigated behavioural changes. Overall, the self-reported likelihood of accepting vaccination against novel H1N1 was 54.7% (343/627). CONCLUSIONS: While, most participants did not believe they were at high risk of acquiring pandemic H1N1 2009, over half of the sample indicated that they would accept the vaccine. Participants who were vaccinated against the seasonal influenza were more likely to receive the H1N1 vaccine. Concerns about safety, the possibility of side effects and the vaccine development process need to be addressed.",2010 Apr 19,"['Seale, Holly', 'Heywood, Anita E', 'McLaws, Mary-Louise', 'Ward, Kirsten F', 'Lowbridge, Chris P', 'Van, Debbie', 'MacIntyre, C Raina']",BMC Infect Dis,,,True
859e22ac7ded4f546d8f58cc6d8515bd261b5289,PMC,Anatomy of the Epidemiological Literature on the 2003 SARS Outbreaks in Hong Kong and Toronto: A Time-Stratified Review,http://dx.doi.org/10.1371/journal.pmed.1000272,PMC2864302,20454570,CC BY,"BACKGROUND: Outbreaks of emerging infectious diseases, especially those of a global nature, require rapid epidemiological analysis and information dissemination. The final products of those activities usually comprise internal memoranda and briefs within public health authorities and original research published in peer-reviewed journals. Using the 2003 severe acute respiratory syndrome (SARS) epidemic as an example, we conducted a comprehensive time-stratified review of the published literature to describe the different types of epidemiological outputs. METHODS AND FINDINGS: We identified and analyzed all published articles on the epidemiology of the SARS outbreak in Hong Kong or Toronto. The analysis was stratified by study design, research domain, data collection, and analytical technique. We compared the SARS-case and matched-control non-SARS articles published according to the timeline of submission, acceptance, and publication. The impact factors of the publishing journals were examined according to the time of publication of SARS articles, and the numbers of citations received by SARS-case and matched-control articles submitted during and after the epidemic were compared. Descriptive, analytical, theoretical, and experimental epidemiology concerned, respectively, 54%, 30%, 11%, and 6% of the studies. Only 22% of the studies were submitted, 8% accepted, and 7% published during the epidemic. The submission-to-acceptance and acceptance-to-publication intervals of the SARS articles submitted during the epidemic period were significantly shorter than the corresponding intervals of matched-control non-SARS articles published in the same journal issues (p<0.001 and p<0.01, respectively). The differences of median submission-to-acceptance intervals and median acceptance-to-publication intervals between SARS articles and their corresponding control articles were 106.5 d (95% confidence interval [CI] 55.0–140.1) and 63.5 d (95% CI 18.0–94.1), respectively. The median numbers of citations of the SARS articles submitted during the epidemic and over the 2 y thereafter were 17 (interquartile range [IQR] 8.0–52.0) and 8 (IQR 3.2–21.8), respectively, significantly higher than the median numbers of control article citations (15, IQR 8.5–16.5, p<0.05, and 7, IQR 3.0–12.0, p<0.01, respectively). CONCLUSIONS: A majority of the epidemiological articles on SARS were submitted after the epidemic had ended, although the corresponding studies had relevance to public health authorities during the epidemic. To minimize the lag between research and the exigency of public health practice in the future, researchers should consider adopting common, predefined protocols and ready-to-use instruments to improve timeliness, and thus, relevance, in addition to standardizing comparability across studies. To facilitate information dissemination, journal managers should reengineer their fast-track channels, which should be adapted to the purpose of an emerging outbreak, taking into account the requirement of high standards of quality for scientific journals and competition with other online resources. Please see later in the article for the Editors' Summary",2010 May 4,"['Xing, Weijia', 'Hejblum, Gilles', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Med,,,True
5ac30e981ededacfc6671f36634a88e6ce139e39,PMC,Anatomy of the Epidemiological Literature on the 2003 SARS Outbreaks in Hong Kong and Toronto: A Time-Stratified Review,http://dx.doi.org/10.1371/journal.pmed.1000272,PMC2864302,20454570,CC BY,"BACKGROUND: Outbreaks of emerging infectious diseases, especially those of a global nature, require rapid epidemiological analysis and information dissemination. The final products of those activities usually comprise internal memoranda and briefs within public health authorities and original research published in peer-reviewed journals. Using the 2003 severe acute respiratory syndrome (SARS) epidemic as an example, we conducted a comprehensive time-stratified review of the published literature to describe the different types of epidemiological outputs. METHODS AND FINDINGS: We identified and analyzed all published articles on the epidemiology of the SARS outbreak in Hong Kong or Toronto. The analysis was stratified by study design, research domain, data collection, and analytical technique. We compared the SARS-case and matched-control non-SARS articles published according to the timeline of submission, acceptance, and publication. The impact factors of the publishing journals were examined according to the time of publication of SARS articles, and the numbers of citations received by SARS-case and matched-control articles submitted during and after the epidemic were compared. Descriptive, analytical, theoretical, and experimental epidemiology concerned, respectively, 54%, 30%, 11%, and 6% of the studies. Only 22% of the studies were submitted, 8% accepted, and 7% published during the epidemic. The submission-to-acceptance and acceptance-to-publication intervals of the SARS articles submitted during the epidemic period were significantly shorter than the corresponding intervals of matched-control non-SARS articles published in the same journal issues (p<0.001 and p<0.01, respectively). The differences of median submission-to-acceptance intervals and median acceptance-to-publication intervals between SARS articles and their corresponding control articles were 106.5 d (95% confidence interval [CI] 55.0–140.1) and 63.5 d (95% CI 18.0–94.1), respectively. The median numbers of citations of the SARS articles submitted during the epidemic and over the 2 y thereafter were 17 (interquartile range [IQR] 8.0–52.0) and 8 (IQR 3.2–21.8), respectively, significantly higher than the median numbers of control article citations (15, IQR 8.5–16.5, p<0.05, and 7, IQR 3.0–12.0, p<0.01, respectively). CONCLUSIONS: A majority of the epidemiological articles on SARS were submitted after the epidemic had ended, although the corresponding studies had relevance to public health authorities during the epidemic. To minimize the lag between research and the exigency of public health practice in the future, researchers should consider adopting common, predefined protocols and ready-to-use instruments to improve timeliness, and thus, relevance, in addition to standardizing comparability across studies. To facilitate information dissemination, journal managers should reengineer their fast-track channels, which should be adapted to the purpose of an emerging outbreak, taking into account the requirement of high standards of quality for scientific journals and competition with other online resources. Please see later in the article for the Editors' Summary",2010 May 4,"['Xing, Weijia', 'Hejblum, Gilles', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Med,,,False
936d646d345dd1d9e2df55574f53ebae22c29146,PMC,Anatomy of the Epidemiological Literature on the 2003 SARS Outbreaks in Hong Kong and Toronto: A Time-Stratified Review,http://dx.doi.org/10.1371/journal.pmed.1000272,PMC2864302,20454570,CC BY,"BACKGROUND: Outbreaks of emerging infectious diseases, especially those of a global nature, require rapid epidemiological analysis and information dissemination. The final products of those activities usually comprise internal memoranda and briefs within public health authorities and original research published in peer-reviewed journals. Using the 2003 severe acute respiratory syndrome (SARS) epidemic as an example, we conducted a comprehensive time-stratified review of the published literature to describe the different types of epidemiological outputs. METHODS AND FINDINGS: We identified and analyzed all published articles on the epidemiology of the SARS outbreak in Hong Kong or Toronto. The analysis was stratified by study design, research domain, data collection, and analytical technique. We compared the SARS-case and matched-control non-SARS articles published according to the timeline of submission, acceptance, and publication. The impact factors of the publishing journals were examined according to the time of publication of SARS articles, and the numbers of citations received by SARS-case and matched-control articles submitted during and after the epidemic were compared. Descriptive, analytical, theoretical, and experimental epidemiology concerned, respectively, 54%, 30%, 11%, and 6% of the studies. Only 22% of the studies were submitted, 8% accepted, and 7% published during the epidemic. The submission-to-acceptance and acceptance-to-publication intervals of the SARS articles submitted during the epidemic period were significantly shorter than the corresponding intervals of matched-control non-SARS articles published in the same journal issues (p<0.001 and p<0.01, respectively). The differences of median submission-to-acceptance intervals and median acceptance-to-publication intervals between SARS articles and their corresponding control articles were 106.5 d (95% confidence interval [CI] 55.0–140.1) and 63.5 d (95% CI 18.0–94.1), respectively. The median numbers of citations of the SARS articles submitted during the epidemic and over the 2 y thereafter were 17 (interquartile range [IQR] 8.0–52.0) and 8 (IQR 3.2–21.8), respectively, significantly higher than the median numbers of control article citations (15, IQR 8.5–16.5, p<0.05, and 7, IQR 3.0–12.0, p<0.01, respectively). CONCLUSIONS: A majority of the epidemiological articles on SARS were submitted after the epidemic had ended, although the corresponding studies had relevance to public health authorities during the epidemic. To minimize the lag between research and the exigency of public health practice in the future, researchers should consider adopting common, predefined protocols and ready-to-use instruments to improve timeliness, and thus, relevance, in addition to standardizing comparability across studies. To facilitate information dissemination, journal managers should reengineer their fast-track channels, which should be adapted to the purpose of an emerging outbreak, taking into account the requirement of high standards of quality for scientific journals and competition with other online resources. Please see later in the article for the Editors' Summary",2010 May 4,"['Xing, Weijia', 'Hejblum, Gilles', 'Leung, Gabriel M.', 'Valleron, Alain-Jacques']",PLoS Med,,,True
a4ee99345c99a1f9806c8d17dc7e6accaf5309d6,PMC,Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy,http://dx.doi.org/10.1155/2010/723798,PMC2864512,20454584,CC BY,"Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.",2010 May 5,"['Wu, Han-Chung', 'Chang, De-Kuan']",J Oncol,,,True
c9b0389a55de2f9cbfe37049d1072e0984613923,PMC,Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection,http://dx.doi.org/10.1371/journal.ppat.1000893,PMC2865525,20463814,CC BY,"The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI) exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, β-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA) occurred as early as 5–7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha–1-antitrypsin (AAT), termed virus inhibitory peptide (VIRIP), was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.",2010 May 6,"['Kramer, Holger B.', 'Lavender, Kerry J.', 'Qin, Li', 'Stacey, Andrea R.', 'Liu, Michael K. P.', 'di Gleria, Katalin', 'Simmons, Alison', 'Gasper-Smith, Nancy', 'Haynes, Barton F.', 'McMichael, Andrew J.', 'Borrow, Persephone', 'Kessler, Benedikt M.']",PLoS Pathog,,,True
f34ff3679970e1119e87bc6df13848be35a217a4,PMC,Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection,http://dx.doi.org/10.1371/journal.ppat.1000893,PMC2865525,20463814,CC BY,"The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI) exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, β-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA) occurred as early as 5–7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha–1-antitrypsin (AAT), termed virus inhibitory peptide (VIRIP), was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.",2010 May 6,"['Kramer, Holger B.', 'Lavender, Kerry J.', 'Qin, Li', 'Stacey, Andrea R.', 'Liu, Michael K. P.', 'di Gleria, Katalin', 'Simmons, Alison', 'Gasper-Smith, Nancy', 'Haynes, Barton F.', 'McMichael, Andrew J.', 'Borrow, Persephone', 'Kessler, Benedikt M.']",PLoS Pathog,,,False
97c030ade92e5f7583a228b3332b848e1825cb6d,PMC,Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection,http://dx.doi.org/10.1371/journal.ppat.1000893,PMC2865525,20463814,CC BY,"The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI) exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, β-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA) occurred as early as 5–7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha–1-antitrypsin (AAT), termed virus inhibitory peptide (VIRIP), was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.",2010 May 6,"['Kramer, Holger B.', 'Lavender, Kerry J.', 'Qin, Li', 'Stacey, Andrea R.', 'Liu, Michael K. P.', 'di Gleria, Katalin', 'Simmons, Alison', 'Gasper-Smith, Nancy', 'Haynes, Barton F.', 'McMichael, Andrew J.', 'Borrow, Persephone', 'Kessler, Benedikt M.']",PLoS Pathog,,,False
eaa85bd1e79e97031aa9a666081d4ad550381fef,PMC,Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection,http://dx.doi.org/10.1371/journal.ppat.1000893,PMC2865525,20463814,CC BY,"The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI) exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, β-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA) occurred as early as 5–7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha–1-antitrypsin (AAT), termed virus inhibitory peptide (VIRIP), was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.",2010 May 6,"['Kramer, Holger B.', 'Lavender, Kerry J.', 'Qin, Li', 'Stacey, Andrea R.', 'Liu, Michael K. P.', 'di Gleria, Katalin', 'Simmons, Alison', 'Gasper-Smith, Nancy', 'Haynes, Barton F.', 'McMichael, Andrew J.', 'Borrow, Persephone', 'Kessler, Benedikt M.']",PLoS Pathog,,,False
e4007988dba3dcfa65314d50324bdff1ba7f55c2,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,True
dd84d0eafb5b8a5eaaa188b96cee26d26cafce9b,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,False
1d48922e36416e5ca9ccc82b36e08c6141e122ae,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,False
242dcea1de6547489b801ddac02df1d76dfed56e,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,False
79c01be9a0994df6f3574664c006f27f64d95c91,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,False
a20dd031ddcc9073931bc7021026cbce2d331441,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,False
972358c8d4c09b7ace5d8869323a225e41d13c59,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,False
9ceb55e16e0547f12dd8f895b3781a05429fd7b2,PMC,Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing,http://dx.doi.org/10.1371/journal.ppat.1000896,PMC2865531,20463816,CC BY,"Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.",2010 May 6,"['Eckerle, Lance D.', 'Becker, Michelle M.', 'Halpin, Rebecca A.', 'Li, Kelvin', 'Venter, Eli', 'Lu, Xiaotao', 'Scherbakova, Sana', 'Graham, Rachel L.', 'Baric, Ralph S.', 'Stockwell, Timothy B.', 'Spiro, David J.', 'Denison, Mark R.']",PLoS Pathog,,,False
241ba286b5b231ad009c7e9a28c85aacbdff49a9,PMC,Combined analysis of cell growth and apoptosis-regulating proteins in HPVs associated anogenital tumors,http://dx.doi.org/10.1186/1471-2407-10-118,PMC2868050,20346172,CC BY,"BACKGROUND: The clinical course of human papillomavirus (HPV) associated with Bowenoid papulosis and condyloma acuminatum of anogenital tumors are still unknown. Here we evaluated molecules that are relevant to cellular proliferation and regulation of apoptosis in HPV associated anogenital tumors. METHODS: We investigated the levels of telomerase activity, and inhibitor of apoptosis proteins (IAPs) family (c-IAP1, c-IAP2, XIAP) and c-Myc mRNA expression levels in 20 specimens of Bowenoid papulosis and 36 specimens of condyloma acuminatum in anogenital areas. Overall, phosphorylated (p-) AKT, p-ribosomal protein S6 (S6) and p-4E-binding protein 1 (4EBP1) expression levels were examined by immunohistochemistry in anogenital tumors both with and without positive telomerase activity. RESULTS: Positive telomerase activity was detected in 41.7% of Bowenoid papulosis and 27.3% of condyloma acuminatum compared to normal skin (p < 0.001). In contrast, the expression levels of Bowenoid papulosis indicated that c-IAP1, c-IAP2 and XIAP mRNA were significantly upregulated compared to those in both condyloma acuminatum samples (p < 0.001, p < 0.001, p = 0.022, respectively) and normal skin (p < 0.001, p = 0.002, p = 0.034, respectively). Overall, 30% of Bowenoid papulosis with high risk HPV strongly promoted IAPs family and c-Myc but condyloma acuminatum did not significantly activate those genes. Immunohistochemically, p-Akt and p-S6 expressions were associated with positive telomerase activity but not with p-4EBP1 expression. CONCLUSION: Combined analysis of the IAPs family, c-Myc mRNA expression, telomerase activity levels and p-Akt/p-S6 expressions may provide clinically relevant molecular markers in HPV associated anogenital tumors.",2010 Mar 27,"['Mitsuishi, Tsuyoshi', 'Iwabu, Yukie', 'Tokunaga, Kenzo', 'Sata, Tetsutaro', 'Kaneko, Takehiko', 'Ohara, Kuniaki', 'Ohsawa, Ikuroh', 'Oda, Fumino', 'Yamada, Yuko', 'Kawana, Seiji', 'Ozaki, Kohji', 'Nakatake, Mayuka', 'Yamada, Osamu']",BMC Cancer,,,True
ae3594fcd839554d0a4ea161dc9bbd3d1f6dbaa9,PMC,Proper Distance Metrics for Phylogenetic Analysis Using Complete Genomes without Sequence Alignment,http://dx.doi.org/10.3390/ijms11031141,PMC2869232,20480005,CC BY,A shortcoming of most correlation distance methods based on the composition vectors without alignment developed for phylogenetic analysis using complete genomes is that the “distances” are not proper distance metrics in the strict mathematical sense. In this paper we propose two new correlation-related distance metrics to replace the old one in our dynamical language approach. Four genome datasets are employed to evaluate the effects of this replacement from a biological point of view. We find that the two proper distance metrics yield trees with the same or similar topologies as/to those using the old “distance” and agree with the tree of life based on 16S rRNA in a majority of the basic branches. Hence the two proper correlation-related distance metrics proposed here improve our dynamical language approach for phylogenetic analysis.,2010 Mar 18,"['Yu, Zu-Guo', 'Zhan, Xiao-Wen', 'Han, Guo-Sheng', 'Wang, Roger W.', 'Anh, Vo', 'Chu, Ka Hou']",Int J Mol Sci,,,True
2181d2f31f1f4b8c6203668dee4f6b3f382af799,PMC,QSAR Studies on Andrographolide Derivatives as α-Glucosidase Inhibitors,http://dx.doi.org/10.3390/ijms11030880,PMC2869241,20479989,CC BY,"Andrographolide derivatives were shown to inhibit α-glucosidase. To investigate the relationship between activities and structures of andrographolide derivatives, a training set was chosen from 25 andrographolide derivatives by the principal component analysis (PCA) method, and a quantitative structure-activity relationship (QSAR) was established by 2D and 3D QSAR methods. The cross-validation r(2) (0.731) and standard error (0.225) illustrated that the 2D-QSAR model was able to identify the important molecular fragments and the cross-validation r(2) (0.794) and standard error (0.127) demonstrated that the 3D-QSAR model was capable of exploring the spatial distribution of important fragments. The obtained results suggested that proposed combination of 2D and 3D QSAR models could be useful in predicting the α-glucosidase inhibiting activity of andrographolide derivatives.",2010 Mar 2,"['Xu, Jun', 'Huang, Sichao', 'Luo, Haibin', 'Li, Guoji', 'Bao, Jiaolin', 'Cai, Shaohui', 'Wang, Yuqiang']",Int J Mol Sci,,,True
6522e893e7f5739f96db413b61932c949e5fad2d,PMC,A Single Immunization with Soluble Recombinant Trimeric Hemagglutinin Protects Chickens against Highly Pathogenic Avian Influenza Virus H5N1,http://dx.doi.org/10.1371/journal.pone.0010645,PMC2871037,20498717,CC BY,"BACKGROUND: The highly pathogenic avian influenza (HPAI) virus H5N1 causes multi-organ disease and death in poultry, resulting in significant economic losses in the poultry industry. In addition, it poses a major public health threat as it can be transmitted directly from infected poultry to humans with very high (60%) mortality rate. Effective vaccination against HPAI H5N1 would protect commercial poultry and would thus provide an important control measure by reducing the likelihood of bird-to-bird and bird-to-human transmission. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we evaluated the vaccine potential of recombinant soluble trimeric subtype 5 hemagglutinin (sH5(3)) produced in mammalian cells. The secreted, purified sH5(3) was biologically active as demonstrated by its binding to ligands in a sialic acid-dependent manner. It was shown to protect chickens, in a dose-dependent manner, against a lethal challenge with H5N1 after a single vaccination. Protected animals did not shed challenge virus as determined by a quantitative RT-PCR on RNA isolated from trachea and cloaca swabs. Also in mice, vaccination with sH5(3) provided complete protection against challenge with HPAI H5N1. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that sH5(3) constitutes an attractive vaccine antigen for protection of chickens and mammals against HPAI H5N1. As these recombinant soluble hemagglutinin preparations can be produced with high yields and with relatively short lead time, they enable a rapid response to circulating and potentially pandemic influenza viruses.",2010 May 14,"['Cornelissen, Lisette A. H. M.', 'de Vries, Robert P.', 'de Boer-Luijtze, Els A.', 'Rigter, Alan', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",PLoS One,,,True
b747413330a7699f64ee1acbc773808fba975fb3,PMC,Hospital Triage System for Adult Patients Using an Influenza-Like Illness Scoring System during the 2009 Pandemic—Mexico,http://dx.doi.org/10.1371/journal.pone.0010658,PMC2871038,20498718,CC0,"BACKGROUND: Pandemic influenza A (H1N1) virus emerged during 2009. To help clinicians triage adults with acute respiratory illness, a scoring system for influenza-like illness (ILI) was implemented at Hospital Civil de Guadalajara, Mexico. METHODS: A medical history, laboratory and radiology results were collected on emergency room (ER) patients with acute respiratory illness to calculate an ILI-score. Patients were evaluated for admission by their ILI-score and clinicians' assessment of risk for developing complications. Nasal and throat swabs were collected from intermediate and high-risk patients for influenza testing by RT-PCR. The disposition and ILI-score of those oseltamivir-treated versus untreated, clinical characteristics of 2009 pandemic influenza A (H1N1) patients versus test-negative patients were compared by Pearson's Χ(2), Fisher's Exact, and Wilcoxon rank-sum tests. RESULTS: Of 1840 ER patients, 230 were initially hospitalized (mean ILI-score = 15), and the rest were discharged, including 286 ambulatory patients given oseltamivir (median ILI-score = 11), and 1324 untreated (median ILI-score = 5). Fourteen (1%) untreated patients returned, and 3 were hospitalized on oseltamivir (median ILI-score = 19). Of 371 patients tested by RT-PCR, 104 (28%) had pandemic influenza and 42 (11%) had seasonal influenza A detected. Twenty (91%) of 22 imaged hospitalized pandemic influenza patients had bilateral infiltrates compared to 23 (38%) of 61 imaged hospital test-negative patients (p<0.001). One patient with confirmed pandemic influenza presented 6 days after symptom onset, required mechanical ventilation, and died. CONCLUSIONS: The triaging system that used an ILI-score complimented clinicians' judgment of who needed oseltamivir and inpatient care and helped hospital staff manage a surge in demand for services.",2010 May 14,"['Rodriguez-Noriega, Eduardo', 'Gonzalez-Diaz, Esteban', 'Morfin-Otero, Rayo', 'Gomez-Abundis, Gerardo F.', 'Briseño-Ramirez, Jaime', 'Perez-Gomez, Hector Raul', 'Lopez-Gatell, Hugo', 'Alpuche-Aranda, Celia M.', 'Ramírez, Ernesto', 'López, Irma', 'Iguala, Miguel', 'Chapela, Ietza Bojórquez', 'Zavala, Ethel Palacios', 'Hernández, Mauricio', 'Stuart, Tammy L.', 'Villarino, Margarita Elsa', 'Widdowson, Marc-Alain', 'Waterman, Steve', 'Uyeki, Timothy', 'Azziz-Baumgartner, Eduardo', None, None]",PLoS One,,,True
3ed3ca15292f7b5c1ace98e0cece9a60609d8138,PMC,CEACAM1 recognition by bacterial pathogens is species-specific,http://dx.doi.org/10.1186/1471-2180-10-117,PMC2871271,20406467,CC BY,"BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), an immunoglobulin (Ig)-related glycoprotein, serves as cellular receptor for a variety of Gram-negative bacterial pathogens associated with the human mucosa. In particular, Neisseria gonorrhoeae, N. meningitidis, Moraxella catarrhalis, and Haemophilus influenzae possess well-characterized CEACAM1-binding adhesins. CEACAM1 is typically involved in cell-cell attachment, epithelial differentiation, neovascularisation and regulation of T-cell proliferation, and is one of the few CEACAM family members with homologues in different mammalian lineages. However, it is unknown whether bacterial adhesins of human pathogens can recognize CEACAM1 orthologues from other mammals. RESULTS: Sequence comparisons of the amino-terminal Ig-variable-like domain of CEACAM1 reveal that the highest sequence divergence between human, murine, canine and bovine orthologues is found in the β-strands comprising the bacteria-binding CC'FG-face of the Ig-fold. Using GFP-tagged, soluble amino-terminal domains of CEACAM1, we demonstrate that bacterial pathogens selectively associate with human, but not other mammalian CEACAM1 orthologues. Whereas full-length human CEACAM1 can mediate internalization of Neisseria gonorrhoeae in transfected cells, murine CEACAM1 fails to support bacterial internalization, demonstrating that the sequence divergence of CEACAM1 orthologues has functional consequences with regard to bacterial recognition and cellular invasion. CONCLUSIONS: Our results establish the selective interaction of several human-restricted bacterial pathogens with human CEACAM1 and suggest that co-evolution of microbial adhesins with their corresponding receptors on mammalian cells contributes to the limited host range of these highly adapted infectious agents.",2010 Apr 20,"['Voges, Maike', 'Bachmann, Verena', 'Kammerer, Robert', 'Gophna, Uri', 'Hauck, Christof R']",BMC Microbiol,,,True
4922ec2dbaef5cf37c816d3b8bf8ef2003466949,PMC,The Impact of Schistosoma japonicum Infection and Treatment on Ultrasound-Detectable Morbidity: A Five-Year Cohort Study in Southwest China,http://dx.doi.org/10.1371/journal.pntd.0000685,PMC2872638,20502515,CC BY,"BACKGROUND: Ultrasonography allows for non-invasive examination of the liver and spleen and can further our understanding of schistosomiasis morbidity. METHODOLOGY/PRINCIPAL FINDINGS: We followed 578 people in Southwest China for up to five years. Participants were tested for Schistosoma japonicum infection in stool and seven standard measures of the liver and spleen were obtained using ultrasound to evaluate the relationship between schistosomiasis infection and ultrasound-detectable pathology, and the impact of targeted treatment on morbidity. Parenchymal fibrosis, a network pattern of the liver unique to S. japonicum, was associated with infection at the time of ultrasound (OR 1.40, 95% CI: 1.03–1.90) and infection intensity (test for trend, p = 0.002), adjusting for age, sex and year, and more strongly associated with prior infection status and intensity (adjusted OR 1.84, 95% CI: 1.30–2.60; test for trend: p<0.001 respectively), despite prompt treatment of infections. While declines in parenchymal fibrosis over time were statistically significant, only 28% of individuals with severe parenchymal fibrosis (grades 2 or 3) at enrollment reversed to normal or grade 1 within five years. Other liver abnormalities were less consistently associated with S. japonicum infection. CONCLUSIONS/SIGNIFICANCE: Parenchymal fibrosis is an appropriate measure of S. japonicum morbidity and can document reductions in disease following control efforts. Other ultrasound measures may have limited epidemiological value in regions with similar infection levels. Because severe fibrosis may not reverse quickly following treatment, efforts to reduce exposure to S. japonicum should be considered in combination with treatment to prevent schistosomiasis morbidity.",2010 May 18,"['Carlton, Elizabeth J.', 'Hsiang, Michelle', 'Zhang, Yi', 'Johnson, Sarah', 'Hubbard, Alan', 'Spear, Robert C.']",PLoS Negl Trop Dis,,,True
2246e28681bde69c65dc9081df367bb661997f19,PMC,"Secondary Syphilis in Cali, Colombia: New Concepts in Disease Pathogenesis",http://dx.doi.org/10.1371/journal.pntd.0000690,PMC2872645,20502522,CC0,"Venereal syphilis is a multi-stage, sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum (Tp). Herein we describe a cohort of 57 patients (age 18–68 years) with secondary syphilis (SS) identified through a network of public sector primary health care providers in Cali, Colombia. To be eligible for participation, study subjects were required to have cutaneous lesions consistent with SS, a reactive Rapid Plasma Reagin test (RPR-titer ≥1∶4), and a confirmatory treponemal test (Fluorescent Treponemal Antibody Absorption test- FTA-ABS). Most subjects enrolled were women (64.9%), predominantly Afro-Colombian (38.6%) or mestizo (56.1%), and all were of low socio-economic status. Three (5.3%) subjects were newly diagnosed with HIV infection at study entry. The duration of signs and symptoms in most patients (53.6%) was less than 30 days; however, some patients reported being symptomatic for several months (range 5–240 days). The typical palmar and plantar exanthem of SS was the most common dermal manifestation (63%), followed by diffuse hypo- or hyperpigmented macules and papules on the trunk, abdomen and extremities. Three patients had patchy alopecia. Whole blood (WB) samples and punch biopsy material from a subset of SS patients were assayed for the presence of Tp DNA polymerase I gene (polA) target by real-time qualitative and quantitative PCR methods. Twelve (46%) of the 26 WB samples studied had quantifiable Tp DNA (ranging between 194.9 and 1954.2 Tp polA copies/ml blood) and seven (64%) were positive when WB DNA was extracted within 24 hours of collection. Tp DNA was also present in 8/12 (66%) skin biopsies available for testing. Strain typing analysis was attempted in all skin and WB samples with detectable Tp DNA. Using arp repeat size analysis and tpr RFLP patterns four different strain types were identified (14d, 16d, 13d and 22a). None of the WB samples had sufficient DNA for typing. The clinical and microbiologic observations presented herein, together with recent Cali syphilis seroprevalence data, provide additional evidence that venereal syphilis is highly endemic in this region of Colombia, thus underscoring the need for health care providers in the region to be acutely aware of the clinical manifestations of SS. This study also provides, for the first time, quantitative evidence that a significant proportion of untreated SS patients have substantial numbers of circulating spirochetes. How Tp is able to persist in the blood and skin of SS patients, despite the known presence of circulating treponemal opsonizing antibodies and the robust pro-inflammatory cellular immune responses characteristic of this stage of the disease, is not fully understood and requires further study.",2010 May 18,"['Cruz, Adriana R.', 'Pillay, Allan', 'Zuluaga, Ana V.', 'Ramirez, Lady G.', 'Duque, Jorge E.', 'Aristizabal, Gloria E.', 'Fiel-Gan, Mary D.', 'Jaramillo, Roberto', 'Trujillo, Rodolfo', 'Valencia, Carlos', 'Jagodzinski, Linda', 'Cox, David L.', 'Radolf, Justin D.', 'Salazar, Juan C.']",PLoS Negl Trop Dis,,,True
759978859d988aaba2d6dcfde90663d797f89550,PMC,Reduction of Natural Killer but Not Effector CD8 T Lymphoyctes in Three Consecutive Cases of Severe/Lethal H1N1/09 Influenza A Virus Infection,http://dx.doi.org/10.1371/journal.pone.0010675,PMC2872666,20502691,CC BY,"BACKGROUND: The cause of severe disease in some patients infected with pandemic influenza A virus is unclear. METHODOLOGY/PRINCIPAL FINDINGS: We present the cellular immunology profile in the blood, and detailed clinical (and post-mortem) findings of three patients with rapidly progressive infection, including a pregnant patient who died. The striking finding is of reduction in natural killer (NK) cells but preservation of activated effector CD8 T lymphocytes; with viraemia in the patient who had no NK cells. Comparison with control groups suggests that the reduction of NK cells is unique to these severely ill patients. CONCLUSION/SIGNIFICANCE: Our report shows markedly reduced NK cells in the three patients that we sampled and raises the hypothesis that NK may have a more significant role than T lymphocytes in controlling viral burden when the host is confronted with a new influenza A virus subtype.",2010 May 18,"['Denney, Laura', 'Aitken, Celia', 'Li, Chris Ka-Fai', 'Wilson-Davies, Eleri', 'Kok, Wai Ling', 'Clelland, Colin', 'Rooney, Kevin', 'Young, Duncan', 'Dong, Tao', 'McMichael, Andrew J.', 'Carman, William F.', 'Ho, Ling-Pei']",PLoS One,,,True
43eaa4d7209e389a360aeab2b3b44e76fd89f5c2,PMC,An evaluation of potential reference genes for stability of expression in two salmonid cell lines after infection with either Piscirickettsia salmonis or IPNV,http://dx.doi.org/10.1186/1756-0500-3-101,PMC2873344,20398263,CC BY,"BACKGROUND: Due to the limited number of species specific antibodies against fish proteins, differential gene expression analyses are vital for the study of host immune responses. Quantitative real-time reverse transcription PCR (qRT-PCR) is one of the most powerful tools for this purpose. Nevertheless, the accuracy of the method will depend on the careful selection of genes whose expression are stable and can be used as internal controls for a particular experimental setting. FINDINGS: The expression stability of five commonly used housekeeping genes [beta-actin (ACTB), elongation factor 1-alpha (EF1A), ubiquitin (UBQ), glyceraldehyd-3-phosphate dehydrogenase (GAPDH) and tubulin alpha (TUBA)] were monitored in salmonid cell lines CHSE-214 and RTS11 after infection with two of the most fastidious fish pathogens, the facultative bacterium Piscirickettsia salmonis and the aquabirnavirus IPNV (Infectious Pancreatic Necrosis Virus). After geNorm analysis, UBQ and EF1A appeared as the most stable, although EF1A was slightly upregulated at late stages of P. salmonis infection in RTS11. ACTB instead, showed a good performance in each case, being always considered within the three most stable genes of the panel. In contrast, infection-dependent differential regulation of GAPDH and TUBA was also demonstrated. CONCLUSION: Based on the data presented here with the cell culture models CHSE-214 and RTS11, we suggest the initial choice of UBQ, ACTB and EF1A as reference genes in qRT-PCR assays for studying the effect of P. salmonis and IPNV on the host immune response.",2010 Apr 14,"['Peña, Andrea A', 'Bols, Niels C', 'Marshall, Sergio H']",BMC Res Notes,,,True
0877aadd2c55095b8a663597fbb39150614f335e,PMC,Collection by trained pediatricians or parents of mid-turbinate nasal flocked swabs for the detection of influenza viruses in childhood,http://dx.doi.org/10.1186/1743-422X-7-85,PMC2873380,20433729,CC BY,"This study evaluated the efficiency of pediatric mid-turbinate nasal flocked swabs used by parents in 203 children aged 6 months to 5 years with signs and symptoms of respiratory disease. Two nasal samples were collected from each child in a randomised sequence: one by a trained pediatrician and one by a parent. The real-time polymerase chain reaction influenza virus detection rates were similar in the samples collected using the two methods (Cohen's kappa = 0.86), as were the cycle threshold values. In comparison with the pediatrician-collected samples, the sensitivity and specificity of the parental collections were respectively 89.3% (95% confidence interval [CI]: 77.8-100%) and 97.7% (95% CI: 95.5-100%), and the positive and negative predictive values were respectively 86.2% (95% CI: 73.7-95.1%) and 98.2% (95% CI: 96.4-100%). The children were significantly more satisfied with the parental collections (median values ± standard deviation, 1.59 ± 0.55 vs 3.51 ± 0.36; p < 0.0001). These findings show that mid-turbinate nasal flocked swabs specifically designed for infants and children can be used by parents without reducing the influenza virus detection rate. Moreover, the direct involvement of parents significantly increases patient acceptance, thus simplifying collection and suggesting that this novel swab design should be considered for epidemiological surveys and vaccine efficacy studies.",2010 Apr 30,"['Esposito, Susanna', 'Molteni, Claudio G', 'Daleno, Cristina', 'Valzano, Antonia', 'Tagliabue, Claudia', 'Galeone, Carlotta', 'Milani, Gregorio', 'Fossali, Emilio', 'Marchisio, Paola', 'Principi, Nicola']",Virol J,,,True
3c1893f7c0ec143b4f173980381354e5cfe6416f,PMC,"Risk Factors for SARS Transmission from Patients Requiring Intubation: A Multicentre Investigation in Toronto, Canada",http://dx.doi.org/10.1371/journal.pone.0010717,PMC2873403,20502660,CC BY,"BACKGROUND: In the 2003 Toronto SARS outbreak, SARS-CoV was transmitted in hospitals despite adherence to infection control procedures. Considerable controversy resulted regarding which procedures and behaviours were associated with the greatest risk of SARS-CoV transmission. METHODS: A retrospective cohort study was conducted to identify risk factors for transmission of SARS-CoV during intubation from laboratory confirmed SARS patients to HCWs involved in their care. All SARS patients requiring intubation during the Toronto outbreak were identified. All HCWs who provided care to intubated SARS patients during treatment or transportation and who entered a patient room or had direct patient contact from 24 hours before to 4 hours after intubation were eligible for this study. Data was collected on patients by chart review and on HCWs by interviewer-administered questionnaire. Generalized estimating equation (GEE) logistic regression models and classification and regression trees (CART) were used to identify risk factors for SARS transmission. RESULTS: 45 laboratory-confirmed intubated SARS patients were identified. Of the 697 HCWs involved in their care, 624 (90%) participated in the study. SARS-CoV was transmitted to 26 HCWs from 7 patients; 21 HCWs were infected by 3 patients. In multivariate GEE logistic regression models, presence in the room during fiberoptic intubation (OR = 2.79, p = .004) or ECG (OR = 3.52, p = .002), unprotected eye contact with secretions (OR = 7.34, p = .001), patient APACHE II score ≥20 (OR = 17.05, p = .009) and patient Pa0(2)/Fi0(2) ratio ≤59 (OR = 8.65, p = .001) were associated with increased risk of transmission of SARS-CoV. In CART analyses, the four covariates which explained the greatest amount of variation in SARS-CoV transmission were covariates representing individual patients. CONCLUSION: Close contact with the airway of severely ill patients and failure of infection control practices to prevent exposure to respiratory secretions were associated with transmission of SARS-CoV. Rates of transmission of SARS-CoV varied widely among patients.",2010 May 19,"['Raboud, Janet', 'Shigayeva, Altynay', 'McGeer, Allison', 'Bontovics, Erika', 'Chapman, Martin', 'Gravel, Denise', 'Henry, Bonnie', 'Lapinsky, Stephen', 'Loeb, Mark', 'McDonald, L. Clifford', 'Ofner, Marianna', 'Paton, Shirley', 'Reynolds, Donna', 'Scales, Damon', 'Shen, Sandy', 'Simor, Andrew', 'Stewart, Thomas', 'Vearncombe, Mary', 'Zoutman, Dick', 'Green, Karen']",PLoS One,,,True
da2b69c89152ddb6f2df6c836bd84aebba2a0b65,PMC,Transcriptome sequencing and development of an expression microarray platform for the domestic ferret,http://dx.doi.org/10.1186/1471-2164-11-251,PMC2873475,20403183,CC BY,"BACKGROUND: The ferret (Mustela putorius furo) represents an attractive animal model for the study of respiratory diseases, including influenza. Despite its importance for biomedical research, the number of reagents for molecular and immunological analysis is restricted. We present here a parallel sequencing effort to produce an extensive EST (expressed sequence tags) dataset derived from a normalized ferret cDNA library made from mRNA from ferret blood, liver, lung, spleen and brain. RESULTS: We produced more than 500000 sequence reads that were assembled into 16000 partial ferret genes. These genes were combined with the available ferret sequences in the GenBank to develop a ferret specific microarray platform. Using this array, we detected tissue specific expression patterns which were confirmed by quantitative real time PCR assays. We also present a set of 41 ferret genes with even transcription profiles across the tested tissues, indicating their usefulness as housekeeping genes. CONCLUSION: The tools developed in this study allow for functional genomic analysis and make further development of reagents for the ferret model possible.",2010 Apr 19,"['Bruder, Carl E', 'Yao, Suxia', 'Larson, Francis', 'Camp, Jeremy V', 'Tapp, Ronald', 'McBrayer, Alexis', 'Powers, Nicholas', 'Valdivia Granda, Willy', 'Jonsson, Colleen B']",BMC Genomics,,,True
a762208186ddb3827966e6d7bec5a4fb8a0124cf,PMC,Treatment with Imiquimod enhances antitumor immunity induced by therapeutic HPV DNA vaccination,http://dx.doi.org/10.1186/1423-0127-17-32,PMC2873498,20426849,CC BY,"BACKGROUND: There is an urgent need to develop new innovative therapies for the control of advanced cancer. The combination of antigen-specific immunotherapy with the employment of immunomodulatory agents has emerged as a potentially plausible approach for the control of advanced cancer. METHODS: In the current study, we explored the combination of the DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7) with the TLR7 agonist imiquimod for their ability to generate E7-specific immune responses and antitumor effects in tumor-bearing mice. RESULTS: We observed that treatment with CRT/E7 DNA in combination with imiquimod leads to an enhancement in the E7-specific CD8+ T cell immune responses and a decrease in the number of myeloid-derived suppressor cells in the tumor microenvironment of tumor-bearing mice. Furthermore, treatment with CRT/E7 DNA in combination with imiquimod leads to significantly improved antitumor effects and prolonged survival in treated mice. In addition, treatment with imiquimod led to increased number of NK1.1+ cells and F4/80+ cells in the tumor microenvironment. Macrophages and NK1.1+ cells were found to play an important role in the antitumor effects mediated by treatment with CRT/E7 DNA in combination with imiquimod. CONCLUSIONS: Thus, our data suggests that the combination of therapeutic HPV DNA vaccination with topical treatment with the TLR7 agonist imiquimod enhances the antitumor immunity induced by DNA vaccination. The current study has significant implications for future clinical translation.",2010 Apr 28,"['Chuang, Chi-Mu', 'Monie, Archana', 'Hung, Chien-Fu', 'Wu, T-C']",J Biomed Sci,,,True
0469d052ac583aa5b739be7fedecec5307548d49,PMC,Perception of epidemic's related anxiety in the General French Population: a cross-sectional study in the Rhône-Alpes region,http://dx.doi.org/10.1186/1471-2458-10-191,PMC2874530,20385030,CC BY,"BACKGROUND: To efficiently plan appropriate public health interventions during possible epidemics, governments must take into consideration the following factors about the general population: their knowledge of epidemics, their fears of and psychological responses to them, their level of compliance with government measures and their communities' trusted sources of information. However, such surveys among the French general population are rare. METHODS: A cross-sectional study was conducted in 2006 in a representative sample of 600 subjects living in the Rhône-Alpes region (south-east France) to investigate self-reported knowledge about infectious diseases and anxiety generated by epidemic risk with particular reference to avian influenza. Data on reactions to potentially new epidemics and the confidence level in various sources of information were also collected. RESULTS: Respondents were most knowledgeable about AIDS, followed by avian influenza. Overall, 75% of respondents had adequate knowledge of avian influenza. The percentage was even higher (88%) among inhabitants of the Ain district, where an avian influenza epidemic had previously been reported. However, 39% expressed anxiety about this disease. In total, 20% of respondents with knowledge about avian influenza stated that they had changed their behaviours during the epizooty. Epidemics were perceived as a real threat by 27% of respondents. In the event of a highly contagious outbreak, the majority of respondents said they would follow the advice given by authorities. The study population expressed a high level of confidence in physicians and scientists, but had strong reservations about politicians, deputies and the media. CONCLUSIONS: Although the survey was conducted only four months after the avian influenza outbreak, epidemics were not perceived as a major threat by the study population. The results showed that in the event of a highly infectious disease, the population would comply with advice given by public authorities.",2010 Apr 13,"['Saadatian-Elahi, Mitra', 'Facy, Françoise', 'Del Signore, Corinne', 'Vanhems, Philippe']",BMC Public Health,,,True
008c1ceaeffe7abc87b031af39fae2632fa72897,PMC,AMS 3.0: prediction of post-translational modifications,http://dx.doi.org/10.1186/1471-2105-11-210,PMC2874555,20423529,CC BY,"BACKGROUND: We present here the recent update of AMS algorithm for identification of post-translational modification (PTM) sites in proteins based only on sequence information, using artificial neural network (ANN) method. The query protein sequence is dissected into overlapping short sequence segments. Ten different physicochemical features describe each amino acid; therefore nine residues long segment is represented as a point in a 90 dimensional space. The database of sequence segments with confirmed by experiments post-translational modification sites are used for training a set of ANNs. RESULTS: The efficiency of the classification for each type of modification and the prediction power of the method is estimated here using recall (sensitivity), precision values, the area under receiver operating characteristic (ROC) curves and leave-one-out tests (LOOCV). The significant differences in the performance for differently optimized neural networks are observed, yet the AMS 3.0 tool integrates those heterogeneous classification schemes into the single consensus scheme, and it is able to boost the precision and recall values independent of a PTM type in comparison with the currently available state-of-the art methods. CONCLUSIONS: The standalone version of AMS 3.0 presents an efficient way to indentify post-translational modifications for whole proteomes. The training datasets, precompiled binaries for AMS 3.0 tool and the source code are available at http://code.google.com/p/automotifserver under the Apache 2.0 license scheme.",2010 Apr 28,"['Basu, Subhadip', 'Plewczynski, Dariusz']",BMC Bioinformatics,,,True
a533da998e4132f8192e41a197f5d8cd065df996,PMC,"Journals, Academics, and Pandemics",http://dx.doi.org/10.1371/journal.pmed.1000282,PMC2876121,20520802,CC BY,"In the wake of the SARS epidemic and the H1N1 pandemic, the PLoS Medicine editors ask whether journal publishing is an efficient enough mechanism for information sharing.",2010 May 25,,PLoS Med,,,True
e12e72939bfeb49c8865a15d0c1bc9a4f99c0ece,PMC,Rotavirus Structural Proteins and dsRNA Are Required for the Human Primary Plasmacytoid Dendritic Cell IFNα Response,http://dx.doi.org/10.1371/journal.ppat.1000931,PMC2880586,20532161,CC BY,"Rotaviruses are the leading cause of severe dehydrating diarrhea in children worldwide. Rotavirus-induced immune responses, especially the T and B cell responses, have been extensively characterized; however, little is known about innate immune mechanisms involved in the control of rotavirus infection. Although increased levels of systemic type I interferon (IFNα and β) correlate with accelerated resolution of rotavirus disease, multiple rotavirus strains, including rhesus rotavirus (RRV), have been demonstrated to antagonize type I IFN production in a variety of epithelial and fibroblast cell types through several mechanisms, including degradation of multiple interferon regulatory factors by a viral nonstructural protein. This report demonstrates that stimulation of highly purified primary human peripheral plasmacytoid dendritic cells (pDCs) with either live or inactivated RRV induces substantial IFNα production by a subset of pDCs in which RRV does not replicate. Characterization of pDC responses to viral stimulus by flow cytometry and Luminex revealed that RRV replicates in a small subset of human primary pDCs and, in this RRV-permissive small subset, IFNα production is diminished. pDC activation and maturation were observed independently of viral replication and were enhanced in cells in which virus replicates. Production of IFNα by pDCs following RRV exposure required viral dsRNA and surface proteins, but neither viral replication nor activation by trypsin cleavage of VP4. These results demonstrate that a minor subset of purified primary human peripheral pDCs are permissive to RRV infection, and that pDCs retain functionality following RRV stimulus. Additionally, this study demonstrates trypsin-independent infection of primary peripheral cells by rotavirus, which may allow for the establishment of extraintestinal viremia and antigenemia. Importantly, these data provide the first evidence of IFNα induction in primary human pDCs by a dsRNA virus, while simultaneously demonstrating impaired IFNα production in primary human cells in which RRV replicates. Rotavirus infection of primary human pDCs provides a powerful experimental system for the study of mechanisms underlying pDC-mediated innate immunity to viral infection and reveals a potentially novel dsRNA-dependent pathway of IFNα induction.",2010 Jun 3,"['Deal, Emily M.', 'Jaimes, Maria C.', 'Crawford, Sue E.', 'Estes, Mary K.', 'Greenberg, Harry B.']",PLoS Pathog,,,True
8a05548f8c34051d47f568ce2135978de0f9515d,PMC,A multiplex reverse transcription-nested polymerase chain reaction for detection and differentiation of wild-type and vaccine strains of canine distemper virus,http://dx.doi.org/10.1186/1743-422X-7-86,PMC2880969,20433759,CC BY,"A multiplex reverse transcription-nested polymerase chain reaction (RT-nPCR) method was developed for the detection and differentiation of wild-type and vaccine strains of canine distemper virus (CDV). A pair of primers (P1 and P4) specific for CDV corresponding to the highly conserved region of the CDV genome were used as a common primer pair in the first-round PCR of the nested PCR. Primers P2 specific for CDV wild-type strains, were used as the forward primer together with the common reverse primer P4 in the second round of nested PCR. Primers P3, P5 specific for CDV wild-type strain or vaccine strain, were used as the forward primer together with the common reverse primer P4+P6 in the second round of nested PCR. A fragment of 177 bp was amplified from vaccine strain genomic RNA, and a fragment of 247 bp from wild-type strain genomic RNA in the RT-nPCR, and two fragments of 247 bp and 177 bp were amplified from the mixed samples of vaccine and wild-type strains. No amplification was achieved for uninfected cells, or cells infected with Newcastle disease virus (NDV), canine parvovirus (CPV), canine coronavirus (CCV), rabies virus (RV), or canine adenovirus (CAV). The RT-nPCR method was used to detect 30 field samples suspected of canine distemper from Heilongjiang and Jilin Provinces, and 51 samples in Shandong province. As a result of 30 samples, were found to be wild-type-like, and 5 to be vaccine-strain-like. The RT-nPCR method can be used to effectively detect and differentiate wild-type CDV-infected dogs from dogs vaccinated with CDV vaccine, and thus can be used in clinical detection and epidemiological surveillance.",2010 May 1,"['Si, Wei', 'Zhou, Shun', 'Wang, Zhao', 'Cui, Shang-jin']",Virol J,,,True
a71e4139dc4ba7ca03da5d99cac0781f092d5223,PMC,Rapid semi-automated quantitative multiplex tandem PCR (MT-PCR) assays for the differential diagnosis of influenza-like illness,http://dx.doi.org/10.1186/1471-2334-10-113,PMC2881921,20459845,CC BY,"BACKGROUND: Influenza A, including avian influenza, is a major public health threat in developed and developing countries. Rapid and accurate detection is a key component of strategies to contain spread of infection, and the efficient diagnosis of influenza-like-illness is essential to protect health infrastructure in the event of a major influenza outbreak. METHODS: We developed a multiplexed PCR (MT-PCR) assay for the simultaneous diagnosis of respiratory viruses causing influenza-like illness, including the specific recognition of influenza A haemagglutinin subtypes H1, H3, and H5. We tested several hundred clinical specimens in two diagnostic reference laboratories and compared the results with standard techniques. RESULTS: The sensitivity and specificity of these assays was higher than individual assays based on direct antigen detection and standard PCR against a range of control templates and in several hundred clinical specimens. The MT-PCR assays provided differential diagnoses as well as potentially useful quantitation of virus in clinical samples. CONCLUSIONS: MT-PCR is a potentially powerful tool for the differential diagnosis of influenza-like illness in the clinical diagnostic laboratory.",2010 May 11,"['Szewczuk, Elektra', 'Thapa, Kiran', 'Anninos, Terry', 'McPhie, Kenneth', 'Higgins, Geoff', 'Dwyer, Dominic E', 'Stanley, Keith K', 'Iredell, Jonathan R']",BMC Infect Dis,,,True
926d8dc84a667e11dfea30fac3824fd17e175398,PMC,A Crucial Role for Infected-Cell/Antibody Immune Complexes in the Enhancement of Endogenous Antiviral Immunity by Short Passive Immunotherapy,http://dx.doi.org/10.1371/journal.ppat.1000948,PMC2883599,20548955,CC BY,"Antiviral monoclonal antibodies (mAbs) represent promising therapeutics. However, most mAbs-based immunotherapies conducted so far have only considered the blunting of viral propagation and not other possible therapeutic effects independent of virus neutralization, namely the modulation of the endogenous immune response. As induction of long-term antiviral immunity still remains a paramount challenge for treating chronic infections, we have asked here whether neutralizing mAbs can, in addition to blunting viral propagation, exert immunomodulatory effects with protective outcomes. Supporting this idea, we report here that mice infected with the FrCas(E) murine retrovirus on day 8 after birth die of leukemia within 4–5 months and mount a non-protective immune response, whereas those rapidly subjected to short immunotherapy with a neutralizing mAb survive healthy and mount a long-lasting protective antiviral immunity with strong humoral and cellular immune responses. Interestingly, the administered mAb mediates lysis of infected cells through an antibody-dependent cell cytotoxicity (ADCC) mechanism. In addition, it forms immune complexes (ICs) with infected cells that enhance antiviral CTL responses through FcγR-mediated binding to dendritic cells (DCs). Importantly, the endogenous antiviral antibodies generated in mAb-treated mice also display the same properties, allowing containment of viral propagation and enhancement of memory cellular responses after disappearance of the administered mAb. Thus, our data demonstrate that neutralizing antiviral mAbs can act as immunomodulatory agents capable of stimulating a protective immunity lasting long after the end of the treatment. They also show an important role of infected-cells/antibody complexes in the induction and the maintenance of protective immunity through enhancement of both primary and memory antiviral T-cell responses. They also indicate that targeting infected cells, and not just viruses, by antibodies can be crucial for elicitation of efficient, long-lasting antiviral T-cell responses. This must be considered when designing antiviral mAb-based immunotherapies.",2010 Jun 10,"['Michaud, Henri-Alexandre', 'Gomard, Tiphanie', 'Gros, Laurent', 'Thiolon, Kevin', 'Nasser, Roudaina', 'Jacquet, Chantal', 'Hernandez, Javier', 'Piechaczyk, Marc', 'Pelegrin, Mireia']",PLoS Pathog,,,True
dbe74afc075c179f7c6298934ce53e6e6bdae4ea,PMC,Phylogenetic nomenclature and evolution of mannose-binding lectin (MBL2) haplotypes,http://dx.doi.org/10.1186/1471-2156-11-38,PMC2885306,20465856,CC BY,"BACKGROUND: Polymorphisms of the mannose-binding lectin gene (MBL2) affect the concentration and functional efficiency of the protein. We recently used haplotype-specific sequencing to identify 23 MBL2 haplotypes, associated with enhanced susceptibility to several diseases. RESULTS: In this work, we applied the same method in 288 and 470 chromosomes from Gabonese and European adults, respectively, and found three new haplotypes in the last group. We propose a phylogenetic nomenclature to standardize MBL2 studies and found two major phylogenetic branches due to six strongly linked polymorphisms associated with high MBL production. They presented high Fst values and were imbedded in regions with high nucleotide diversity and significant Tajima's D values. Compared to others using small sample sizes and unphased genotypic data, we found differences in haplotyping, frequency estimation, Fu and Li's D* and Fst results. CONCLUSION: Using extensive testing for selective neutrality, we confirmed that stochastic evolutionary factors have had a major role in shaping this polymorphic gene worldwide.",2010 May 14,"['Boldt, Angelica BW', 'Messias-Reason, Iara J', 'Meyer, Diogo', 'Schrago, Carlos G', 'Lang, Florian', 'Lell, Bertrand', 'Dietz, Klaus', 'Kremsner, Peter G', 'Petzl-Erler, Maria Luiza', 'Kun, Jürgen FJ']",BMC Genet,,,True
a5f1fd1f2782b89068dd76bde0acbffc35632895,PMC,"Incorporation of podoplanin into HIV released from HEK-293T cells, but not PBMC, is required for efficient binding to the attachment factor CLEC-2",http://dx.doi.org/10.1186/1742-4690-7-47,PMC2885308,20482880,CC BY,"BACKGROUND: Platelets are associated with HIV in the blood of infected individuals and might modulate viral dissemination, particularly if the virus is directly transmitted into the bloodstream. The C-type lectin DC-SIGN and the novel HIV attachment factor CLEC-2 are expressed by platelets and facilitate HIV transmission from platelets to T-cells. Here, we studied the molecular mechanisms behind CLEC-2-mediated HIV-1 transmission. RESULTS: Binding studies with soluble proteins indicated that CLEC-2, in contrast to DC-SIGN, does not recognize the viral envelope protein, but a cellular factor expressed on kidney-derived 293T cells. Subsequent analyses revealed that the cellular mucin-like membranous glycoprotein podoplanin, a CLEC-2 ligand, was expressed on 293T cells and incorporated into virions released from these cells. Knock-down of podoplanin in 293T cells by shRNA showed that virion incorporation of podoplanin was required for efficient CLEC-2-dependent HIV-1 interactions with cell lines and platelets. Flow cytometry revealed no evidence for podoplanin expression on viable T-cells and peripheral blood mononuclear cells (PBMC). Podoplanin was also not detected on HIV-1 infected T-cells. However, apoptotic bystander cells in HIV-1 infected cultures reacted with anti-podoplanin antibodies, and similar results were obtained upon induction of apoptosis in a cell line and in PBMCs suggesting an unexpected link between apoptosis and podoplanin expression. Despite the absence of detectable podoplanin expression, HIV-1 produced in PBMC was transmitted to T-cells in a CLEC-2-dependent manner, indicating that T-cells might express an as yet unidentified CLEC-2 ligand. CONCLUSIONS: Virion incorporation of podoplanin mediates CLEC-2 interactions of HIV-1 derived from 293T cells, while incorporation of a different cellular factor seems to be responsible for CLEC-2-dependent capture of PBMC-derived viruses. Furthermore, evidence was obtained that podoplanin expression is connected to apoptosis, a finding that deserves further investigation.",2010 May 19,"['Chaipan, Chawaree', 'Steffen, Imke', 'Tsegaye, Theodros Solomon', 'Bertram, Stephanie', 'Glowacka, Ilona', 'Kato, Yukinari', 'Schmökel, Jan', 'Münch, Jan', 'Simmons, Graham', 'Gerardy-Schahn, Rita', 'Pöhlmann, Stefan']",Retrovirology,,,True
34dfd4d983484d85d797e915cb47041aeb4ced86,PMC,An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of Hand Foot and Mouth Disease in Fuyang city of China,http://dx.doi.org/10.1186/1743-422X-7-94,PMC2885340,20459851,CC BY,"Hand, foot and mouth disease (HFMD), a common contagious disease that usually affects children, is normally mild but can have life-threatening manifestations. It can be caused by enteroviruses, particularly Coxsackieviruses and human enterovirus 71 (HEV71) with highly variable clinical manifestations. In the spring of 2008, a large, unprecedented HFMD outbreak in Fuyang city of Anhui province in the central part of southeastern China resulted in a high aggregation of fatal cases. In this study, epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. Of the 6,049 cases reported between 1 March and 9 May of 2008, 3023 (50%) were hospitalized, 353 (5.8%) were severe and 22 (0.36%) were fatal. HEV71 was confirmed as the etiological pathogen of the outbreak. Phylogenetic analyses of entire VP1 capsid protein sequence of 45 Fuyang HEV71 isolates showed that they belong to C4a cluster of the C4 subgenotype. In addition, genetic recombinations were found in the 3D region (RNA-dependent RNA polymerase, a major component of the viral replication complex of the genome) between the Fuyang HEV71 strain and Coxsackievirus A16 (CV-A16), resulting in a recombination virus. In conclusion, an emerging recombinant HEV71 was responsible for the HFMD outbreak in Fuyang City of China, 2008.",2010 May 12,"['Zhang, Yan', 'Zhu, Zhen', 'Yang, Weizhong', 'Ren, Jun', 'Tan, Xiaojuan', 'Wang, Yu', 'Mao, Naiying', 'Xu, Songtao', 'Zhu, Shuangli', 'Cui, Aili', 'Zhang, Yong', 'Yan, Dongmei', 'Li, Qun', 'Dong, Xiaoping', 'Zhang, Jing', 'Zhao, Yueping', 'Wan, Junfeng', 'Feng, Zijian', 'Sun, Junling', 'Wang, Shiwen', 'Li, Dexin', 'Xu, Wenbo']",Virol J,,,True
b1b2eb98641f5fbf2b51cb26566196ae59a7ad96,PMC,Monitoring of risk perceptions and correlates of precautionary behaviour related to human avian influenza during 2006 - 2007 in the Netherlands: results of seven consecutive surveys,http://dx.doi.org/10.1186/1471-2334-10-114,PMC2885389,20462419,CC BY,"BACKGROUND: Avian influenza (AI) is a public health challenge because of ongoing spread and pandemic potential. Non-pharmaceutical measures are important to prevent the spread of AI and to contain a pandemic. The effectiveness of such measures is largely dependent on the behaviour of the population. Risk perception is a central element in changing behaviour. This study aimed to investigate perceived vulnerability, severity and precautionary behaviour related to AI in the Netherlands during seven consecutive surveys in 2006 - 2007 as well as possible trends in risk perception and self-reported precautionary behaviours. METHODS: Seven web-based surveys were conducted including 3,840 respondents over a one-year period. Time trends were analyzed with linear regression analyses. Multivariate analysis was used to study determinants of precautionary behaviour. RESULTS: While infection with AI was considered a very severe health problem with mean score of 4.57 (scale 1 - 5); perceived vulnerability was much lower, with a mean score of 1.69. While perceived severity remained high, perceived vulnerability decreased slightly during a one-year period covering part of 2006 and 2007. Almost half of the respondents (46%) reported taking one or more preventive measures, with 36% reporting to have stayed away from (wild) birds or poultry. In multivariate logistic regression analysis the following factors were significantly associated with taking preventive measures: time of the survey, higher age, lower level of education, non-Dutch ethnicity, vaccinated against influenza, higher perceived severity, higher perceived vulnerability, higher self efficacy, lower level of knowledge, more information about AI, and thinking more about AI. Self efficacy was a stronger predictor of precautionary behaviour for those who never or seldom think about AI (OR 2.3, 95% CI 1.9 - 2.7), compared to those who think about AI more often (OR 1.5, 95% CI 1.2 - 1.9). CONCLUSIONS: The fact that perceived severity of AI appears to be high and remains so over time offers a good point of departure for more specific risk communications to promote precautionary actions. Such communications should aim at improving knowledge about the disease and preventive actions, and focus on perceived personal vulnerability and self efficacy in taking preventive measures.",2010 May 12,"['de Zwart, Onno', 'Veldhuijzen, Irene K', 'Richardus, Jan Hendrik', 'Brug, Johannes']",BMC Infect Dis,,,True
351ea0aee67d40885b15698e3c38134f67590a9a,PMC,Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults,http://dx.doi.org/10.1371/journal.pone.0011088,PMC2885414,20559424,CC BY,"BACKGROUND: Declining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections. This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections. METHODOLOGY/FINDINGS: In this prospective cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009–2010 in 198 healthy adults, blinded to the nature of the substance being measured. The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations. The incidence of infection in participants with different concentrations of vitamin D was determined. One hundred ninety-five (98.5%) of the enrolled participants completed the study. Light skin pigmentation, lean body mass, and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant (p<0.0001) two-fold reduction in the risk of developing acute respiratory tract infections and with a marked reduction in the percentages of days ill. CONCLUSIONS/SIGNIFICANCE: Maintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby, at least during the fall and winter in temperate zones. The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections, including influenza, in the general population and in subpopulations with lower 25-hydroxyvitamin D concentrations, such as pregnant women, dark skinned individuals, and the obese.",2010 Jun 14,"['Sabetta, James R.', 'DePetrillo, Paolo', 'Cipriani, Ralph J.', 'Smardin, Joanne', 'Burns, Lillian A.', 'Landry, Marie L.']",PLoS One,,,True
9bbf07c4bf022a0695b79b87cb4299f6a8d18831,PMC,EST analysis reveals putative genes involved in glycyrrhizin biosynthesis,http://dx.doi.org/10.1186/1471-2164-11-268,PMC2886062,20423525,CC BY,"BACKGROUND: Glycyrrhiza uralensis is one of the most popular medicinal plants in the world and is also widely used in the flavoring of food and tobacco. Due to limited genomic and transcriptomic data, the biosynthetic pathway of glycyrrhizin, the major bioactive compound in G. uralensis, is currently unclear. Identification of candidate genes involved in the glycyrrhizin biosynthetic pathway will significantly contribute to the understanding of the biosynthetic and medicinal chemistry of this compound. RESULTS: We used the 454 GS FLX platform and Titanium regents to produce a substantial expressed sequence tag (EST) dataset from the vegetative organs of G. uralensis. A total of 59,219 ESTs with an average read length of 409 bp were generated. 454 ESTs were combined with the 50,666 G. uralensis ESTs in GenBank. The combined ESTs were assembled into 27,229 unique sequences (11,694 contigs and 15,535 singletons). A total of 20,437 unique gene elements representing approximately 10,000 independent transcripts were annotated using BLAST searches (e-value ≤ 1e-5) against the SwissProt, KEGG, TAIR, Nr and Nt databases. The assembled sequences were annotated with gene names and Gene Ontology (GO) terms. With respect to the genes related to glycyrrhizin metabolism, genes encoding 16 enzymes of the 18 total steps of the glycyrrhizin skeleton synthesis pathway were found. To identify novel genes that encode cytochrome P450 enzymes and glycosyltransferases, which are related to glycyrrhizin metabolism, a total of 125 and 172 unigenes were found to be homologous to cytochrome P450s and glycosyltransferases, respectively. The cytochrome P450 candidate genes were classified into 32 CYP families, while the glycosyltransferase candidate genes were classified into 45 categories by GO analysis. Finally, 3 cytochrome P450 enzymes and 6 glycosyltransferases were selected as the candidates most likely to be involved in glycyrrhizin biosynthesis through an organ-specific expression pattern analysis based on real-time PCR. CONCLUSIONS: Using the 454 GS FLX platform and Titanium reagents, our study provides a high-quality EST database for G. uralensis. Based on the EST analysis, novel candidate genes related to the secondary metabolite pathway of glycyrrhizin, including novel genes encoding cytochrome P450s and glycosyltransferases, were found. With the assistance of organ-specific expression pattern analysis, 3 unigenes encoding cytochrome P450s and 6 unigenes encoding glycosyltransferases were selected as the candidates most likely to be involved in glycyrrhizin biosynthesis.",2010 Apr 28,"['Li, Ying', 'Luo, Hong-Mei', 'Sun, Chao', 'Song, Jing-Yuan', 'Sun, Yong-Zhen', 'Wu, Qiong', 'Wang, Ning', 'Yao, Hui', 'Steinmetz, André', 'Chen, Shi-Lin']",BMC Genomics,,,True
b0eabdda18ddcbe7d2c1ed0932ee123d7eb6dbbf,PMC,Investigating antibody neutralization of lyssaviruses using lentiviral pseudotypes: a cross-species comparison,http://dx.doi.org/10.1099/vir.0.2008/000349-0,PMC2886951,18753230,CC BY,"Cross-neutralization between rabies virus (RABV) and two European bat lyssaviruses (EBLV-1 and -2) was analysed using lentiviral pseudotypes as antigen vectors. Glycoprotein (G-protein) cDNA from RABV challenge virus standard-11 (CVS-11) and EBLV-1 and -2 were cloned and co-expressed with human immunodeficiency virus (HIV) or murine leukemia virus (MLV) gag–pol and packageable green fluorescent protein (GFP) or luciferase reporter genes in human cells. The harvested lentiviral (HIV) vector infected over 40 % of baby hamster kidney (BHK) target cells, providing high-titre pseudotype stocks. Tests on blinded antibody-positive (n=15) and -negative (n=45) sera, predetermined by the fluorescent antibody virus neutralization (FAVN) test approved by the World Health Organization (WHO) and Office International des Epizooties (OIE), revealed that the CVS-11 pseudotype assay had 100 % concordance with FAVN and strongly correlated with neutralization titres (r(2)=0.89). Cross-neutralization tests using sera from RABV-vaccinated humans and animals on pseudotypes with CVS-11, EBLV-1 and EBLV-2 envelopes showed that the relative neutralization titres correlated broadly with the degree of G-protein diversity. Pseudotypes have three major advantages over live-virus neutralization tests: (i) they can be handled in low-biohazard-level laboratories; (ii) the use of reporter genes such as GFP or β-galactosidase will allow the assay to be undertaken at low cost in laboratories worldwide; (iii) each assay requires <10 μl serum. This robust microassay will improve our understanding of the protective humoral immunity that current rabies vaccines confer against emerging lyssaviruses, and will be applicable to surveillance studies, thus helping to control the spread of rabies.",2008 Sep,"['Wright, Edward', 'Temperton, Nigel J.', 'Marston, Denise A.', 'McElhinney, Lorraine M.', 'Fooks, Anthony R.', 'Weiss, Robin A.']",J Gen Virol,,,True
0f258dbe201ef5c1419ecfceeb46634cd8451c8e,PMC,Investigating antibody neutralization of lyssaviruses using lentiviral pseudotypes: a cross-species comparison,http://dx.doi.org/10.1099/vir.0.2008/000349-0,PMC2886951,18753230,CC BY,"Cross-neutralization between rabies virus (RABV) and two European bat lyssaviruses (EBLV-1 and -2) was analysed using lentiviral pseudotypes as antigen vectors. Glycoprotein (G-protein) cDNA from RABV challenge virus standard-11 (CVS-11) and EBLV-1 and -2 were cloned and co-expressed with human immunodeficiency virus (HIV) or murine leukemia virus (MLV) gag–pol and packageable green fluorescent protein (GFP) or luciferase reporter genes in human cells. The harvested lentiviral (HIV) vector infected over 40 % of baby hamster kidney (BHK) target cells, providing high-titre pseudotype stocks. Tests on blinded antibody-positive (n=15) and -negative (n=45) sera, predetermined by the fluorescent antibody virus neutralization (FAVN) test approved by the World Health Organization (WHO) and Office International des Epizooties (OIE), revealed that the CVS-11 pseudotype assay had 100 % concordance with FAVN and strongly correlated with neutralization titres (r(2)=0.89). Cross-neutralization tests using sera from RABV-vaccinated humans and animals on pseudotypes with CVS-11, EBLV-1 and EBLV-2 envelopes showed that the relative neutralization titres correlated broadly with the degree of G-protein diversity. Pseudotypes have three major advantages over live-virus neutralization tests: (i) they can be handled in low-biohazard-level laboratories; (ii) the use of reporter genes such as GFP or β-galactosidase will allow the assay to be undertaken at low cost in laboratories worldwide; (iii) each assay requires <10 μl serum. This robust microassay will improve our understanding of the protective humoral immunity that current rabies vaccines confer against emerging lyssaviruses, and will be applicable to surveillance studies, thus helping to control the spread of rabies.",2008 Sep,"['Wright, Edward', 'Temperton, Nigel J.', 'Marston, Denise A.', 'McElhinney, Lorraine M.', 'Fooks, Anthony R.', 'Weiss, Robin A.']",J Gen Virol,,,False
d00f2e117b4d930186ab62bb1a94f929435f9aaf,PMC,Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2,http://dx.doi.org/10.1099/vir.0.2008/003962-0,PMC2886958,18931070,CC BY,"Although in different groups, the coronaviruses severe acute respiratory syndrome-coronavirus (SARS-CoV) and NL63 use the same receptor, angiotensin converting enzyme (ACE)-2, for entry into the host cell. Despite this common receptor, the consequence of entry is very different; severe respiratory distress in the case of SARS-CoV but frequently only a mild respiratory infection for NL63. Using a wholly recombinant system, we have investigated the ability of each virus receptor-binding protein, spike or S protein, to bind to ACE-2 in solution and on the cell surface. In both assays, we find that the NL63 S protein has a weaker interaction with ACE-2 than the SARS-CoV S protein, particularly in solution binding, but the residues required for contact are similar. We also confirm that the ACE-2-binding site of NL63 S lies between residues 190 and 739. A lower-affinity interaction with ACE-2 might partly explain the different pathological consequences of infection by SARS-CoV and NL63.",2008 Nov,"['Mathewson, Alison C.', 'Bishop, Alexandra', 'Yao, Yongxiu', 'Kemp, Fred', 'Ren, Junyuan', 'Chen, Hongying', 'Xu, Xiaodong', 'Berkhout, Ben', 'van der Hoek, Lia', 'Jones, Ian M.']",J Gen Virol,,,True
f8f601687c9a9a4debc34112cec0165ad81fb15d,PMC,Immune Response to Lactobacillus plantarum Expressing Borrelia burgdorferi OspA Is Modulated by the Lipid Modification of the Antigen,http://dx.doi.org/10.1371/journal.pone.0011199,PMC2887847,20585451,CC BY,"BACKGROUND: Over the past decade there has been increasing interest in the use of lactic acid bacteria as mucosal delivery vehicles for vaccine antigens, microbicides and therapeutics. We investigated the mechanism by which a mucosal vaccine based in recombinant lactic acid bacteria breaks the immunological tolerance of the gut in order to elicit a protective immune response. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed how the lipid modification of OspA affects the localization of the antigen in our delivery vehicle using a number of biochemistry techniques. Furthermore, we examined how OspA-expressing L. plantarum breaks the oral tolerance of the gut by stimulating human intestinal epithelial cells, peripheral blood mononuclear cells and monocyte derived dendritic cells and measuring cytokine production. We show that the leader peptide of OspA targets the protein to the cell envelope of L. plantarum, and it is responsible for protein export across the membrane. Mutation of the lipidation site in OspA redirects protein localization within the cell envelope. Further, we show that lipidated-OspA-expressing L. plantarum does not induce secretion of the pro-inflammatory cytokine IL-8 by intestinal epithelial cells. In addition, it breaks oral tolerance of the gut via Th1/Th2 cell mediated immunity, as shown by the production of pro- and anti-inflammatory cytokines by human dendritic cells, and by the production of IgG2a and IgG1 antibodies, respectively. CONCLUSIONS/SIGNIFICANCE: Lipid modification of OspA expressed in L. plantarum modulates the immune response to this antigen through a Th1/Th2 immune response.",2010 Jun 18,"['del Rio, Beatriz', 'Seegers, Jos F. M. L.', 'Gomes-Solecki, Maria']",PLoS One,,,True
c498ea64810a8da9cb26c48e1f5e96973537338d,PMC,Imported Episodic Rabies Increases Patient Demand for and Physician Delivery of Antirabies Prophylaxis,http://dx.doi.org/10.1371/journal.pntd.0000723,PMC2889823,20582307,CC BY,"BACKGROUND: Imported cases threaten rabies reemergence in rabies-free areas. During 2000–2005, five dog and one human rabies cases were imported into France, a rabies-free country since 2001. The Summer 2004 event led to unprecedented media warnings by the French Public Health Director. We investigated medical practice evolution following the official elimination of rabies in 2001; impact of subsequent episodic rabies importations and national newspaper coverage on demand for and delivery of antirabies prophylaxis; regular transmission of epidemiological developments within the French Antirabies Medical Center (ARMC) network; and ARMC discussions on indications of rabies post-exposure prophylaxis (RPEP). METHODOLOGY/PRINCIPAL FINDINGS: Annual data collected by the National Reference Center for Rabies NRCR (1989–2006) and the exhaustive database (2000–2005) of 56 ARMC were analyzed. Weekly numbers of patients consulting at ARMC and their RPEP- and antirabies-immunoglobulin (ARIG) prescription rates were determined. Autoregressive integrated moving-average modeling and regression with autocorrelated errors were applied to examine how 2000–2005 episodic rabies events and their related national newspaper coverage affected demand for and delivery of RPEP. A slight, continuous decline of rabies-dedicated public health facility attendance was observed from 2000 to 2004. Then, during the Summer 2004 event, patient consultations and RPEP and ARIG prescriptions increased by 84%, 19.7% and 43.4%, respectively. Moreover, elevated medical resource use persisted in 2005, despite communication efforts, without any secondary human or animal case. CONCLUSIONS: Our findings demonstrated appropriate responsiveness to reemerging rabies cases and effective newspaper reporting, as no secondary case occurred. However, the ensuing demand on medical resources had immediate and long-lasting effects on rabies-related public health resources and expenses. Henceforth, when facing such an event, decision-makers must anticipate the broad impact of their media communications to counter the emerging risk on maintaining an optimal public health organization and implement a post-crisis communication strategy.",2010 Jun 22,"['Lardon, Zélie', 'Watier, Laurence', 'Brunet, Audrey', 'Bernède, Claire', 'Goudal, Maryvonne', 'Dacheux, Laurent', 'Rotivel, Yolande', 'Guillemot, Didier', 'Bourhy, Hervé']",PLoS Negl Trop Dis,,,True
f60263668f8bb59ae4bd30498e2f04c18157773e,PMC,Structural Optimization and De Novo Design of Dengue Virus Entry Inhibitory Peptides,http://dx.doi.org/10.1371/journal.pntd.0000721,PMC2889824,20582308,CC0,"Viral fusogenic envelope proteins are important targets for the development of inhibitors of viral entry. We report an approach for the computational design of peptide inhibitors of the dengue 2 virus (DENV-2) envelope (E) protein using high-resolution structural data from a pre-entry dimeric form of the protein. By using predictive strategies together with computational optimization of binding “pseudoenergies”, we were able to design multiple peptide sequences that showed low micromolar viral entry inhibitory activity. The two most active peptides, DN57opt and 1OAN1, were designed to displace regions in the domain II hinge, and the first domain I/domain II beta sheet connection, respectively, and show fifty percent inhibitory concentrations of 8 and 7 µM respectively in a focus forming unit assay. The antiviral peptides were shown to interfere with virus:cell binding, interact directly with the E proteins and also cause changes to the viral surface using biolayer interferometry and cryo-electron microscopy, respectively. These peptides may be useful for characterization of intermediate states in the membrane fusion process, investigation of DENV receptor molecules, and as lead compounds for drug discovery.",2010 Jun 22,"['Costin, Joshua M.', 'Jenwitheesuk, Ekachai', 'Lok, Shee-Mei', 'Hunsperger, Elizabeth', 'Conrads, Kelly A.', 'Fontaine, Krystal A.', 'Rees, Craig R.', 'Rossmann, Michael G.', 'Isern, Sharon', 'Samudrala, Ram', 'Michael, Scott F.']",PLoS Negl Trop Dis,,,True
f021d8bdb3482a6965a104dddb2516d179bd9c34,PMC,Hopefulness predicts resilience after hereditary colorectal cancer genetic testing: a prospective outcome trajectories study,http://dx.doi.org/10.1186/1471-2407-10-279,PMC2891641,20537192,CC BY,"BACKGROUND -: Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC. METHODS -: A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer Registry to determine psychological outcomes after genetic testing. Self-completed questionnaires were administered immediately before (pre-disclosure baseline) and 2 weeks, 4 months and 1 year after result disclosure. Using validated psychological inventories, the cognitive style of hope was measured at baseline, and the psychological distress of depression and anxiety was measured at all time points. RESULTS -: Of the 76 participating subjects, 71 individuals (43 men and 28 women; mean age 38.9 ± 9.2 years) from nine FAP and 24 HNPCC families completed the study, including 39 mutated gene carriers. Four patterns of outcome trajectories were created using established norms for the specified outcome measures of depression and anxiety. These included chronic dysfunction (13% and 8.7%), recovery (0% and 4.3%), delayed dysfunction (13% and 15.9%) and resilience (76.8% and 66.7%). Two logistic regression analyses were conducted using hope at baseline to predict resilience, with depression and anxiety employed as outcome indicators. Because of the small number of participants, the chronic dysfunction and delayed dysfunction groups were combined into a non-resilient group for comparison with the resilient group in all subsequent analysis. Because of low frequencies, participants exhibiting a recovery trajectory (n = 3 for anxiety and n = 0 for depression) were excluded from further analysis. Both regression equations were significant. Baseline hope was a significant predictor of a resilience outcome trajectory for depression (B = -0.24, p < 0.01 for depression); and anxiety (B = -0.11, p = 0.05 for anxiety). CONCLUSIONS -: The current findings suggest that hopefulness may predict resilience after HCRC genetic testing in Hong Kong Chinese. Interventions to increase the level of hope may be beneficial to the psychological adjustment of CRC genetic testing recipients.",2010 Jun 11,"['Ho, Samuel MY', 'Ho, Judy WC', 'Bonanno, George A', 'Chu, Annie TW', 'Chan, Emily MS']",BMC Cancer,,,True
68aa709cc13d459268d903c0a505c56dda9bcc81,PMC,Avoidance behaviors and negative psychological responses in the general population in the initial stage of the H1N1 pandemic in Hong Kong,http://dx.doi.org/10.1186/1471-2334-10-139,PMC2891756,20509887,CC BY,"BACKGROUND: During the SARS pandemic in Hong Kong, panic and worry were prevalent in the community and the general public avoided staying in public areas. Such avoidance behaviors could greatly impact daily routines of the community and the local economy. This study examined the prevalence of the avoidance behaviors (i.e. avoiding going out, visiting crowded places and visiting hospitals) and negative psychological responses of the general population in Hong Kong at the initial stage of the H1N1 epidemic. METHODS: A sample of 999 respondents was recruited in a population-based survey. Using random telephone numbers, respondents completed a structured questionnaire by telephone interviews at the 'pre-community spread phase' of the H1N1 epidemic in Hong Kong. RESULTS: This study found that 76.5% of the respondents currently avoided going out or visiting crowded places or hospitals, whilst 15% felt much worried about contracting H1N1 and 6% showed signs of emotional distress. Females, older respondents, those having unconfirmed beliefs about modes of transmissions, and those feeling worried and emotionally distressed due to H1N1 outbreak were more likely than others to adopt some avoidance behaviors. Those who perceived high severity and susceptibility of getting H1N1 and doubted the adequacy of governmental preparedness were more likely than others to feel emotionally distressed. CONCLUSIONS: The prevalence of avoidance behaviors was very high. Cognitions, including unconfirmed beliefs about modes of transmission, perceived severity and susceptibility were associated with some of the avoidance behaviors and emotional distress variables. Public health education should therefore provide clear messages to rectify relevant perceptions.",2010 May 28,"['Lau, Joseph TF', 'Griffiths, Sian', 'Choi, Kai Chow', 'Tsui, Hi Yi']",BMC Infect Dis,,,True
2d78b0600b84cfd57e11ba249ee58c159fe517ae,PMC,"The relationship between antibody status to bovine corona virus and bovine respiratory syncytial virus and disease incidence, reproduction and herd characteristics in dairy herds",http://dx.doi.org/10.1186/1751-0147-52-37,PMC2891787,20525326,CC BY,"BACKGROUND: Bovine respiratory syncytial virus (BRSV) and bovine corona virus (BCV) affects cattle worldwide. Our objective was to evaluate the effects of these infections on general health and reproduction parameters measurable on herd level and to explore the association between antibody status and some herd characteristics. METHODS: We collected a pooled milk sample from five primiparous cows from 79 Swedish dairy herds in September 2006. The samples were analysed for immunoglobulin G antibodies to BCV and BRSV with indirect enzyme-linked immunosorbent assays. Herd level data from 1 September 2005 to 30 August 2006 were accessed retrospectively. The location of the herds was mapped using a geographical information system. RESULTS: Ten herds were antibody negative to both viruses and were compared with 69 herds positive to BCV or BRSV or both. Positive herds had a higher (P = 0.001) bulk tank milk somatic cell count (BMSCC) compared with negative herds. The medians for all other analyzed health and reproductive parameters were consistently in favour of the herds negative to both viruses although the differences were not statistically significant. A higher proportion (P = 0.01) of herds used professional technicians for artificial insemination, rather than farm personnel, amongst the 33 herds negative to BCV compared with the 46 positive herds. CONCLUSIONS: Our result shows that herds that were antibody positive to BCV and/or BRSV had a higher BMSCC compared with herds negative to BCV and BRSV. There was also tendency that negative herds had a better general herd health compared with positive. A higher proportion amongst the BCV negative herds used external technicians for AI instead of farm personnel, indicating that it is possible to avoid infection although having regular visits. Negative herds were located in close proximity to positive herds, indicating that local spread and airborne transmission between herds might not be of great importance and that herds can stay free from these infection transmission although virus is circulating in the area.",2010 Jun 4,"['Ohlson, Anna', 'Emanuelson, Ulf', 'Tråvén, Madeleine', 'Alenius, Stefan']",Acta Vet Scand,,,True
d92ab60000f93cb3e6e10a1055b77224c8e9bae5,PMC,Entry and Fusion of Emerging Paramyxoviruses,http://dx.doi.org/10.1371/journal.ppat.1000881,PMC2891828,20585631,CC BY,,2010 Jun 24,"Dutch, Rebecca Ellis",PLoS Pathog,,,True
9e4f6e2dd8f847c11cc774c7083aa426f42a530e,PMC,Detection of Plant DNA in the Bronchoalveolar Lavage of Patients with Ventilator-Associated Pneumonia,http://dx.doi.org/10.1371/journal.pone.0011298,PMC2891989,20585574,CC BY,"BACKGROUND: Hospital-acquired infections such as nosocomial pneumonia are a serious cause of mortality for hospitalized patients, especially for those admitted to intensive care units (ICUs). Despite the number of the studies reported to date, the causative agents of pneumonia are not completely known. Herein, we found by molecular technique that vegetable and tobacco DNA may be detected in the bronchoalveolar lavage from patients with ventilator-associated pneumonia (VAP). METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we studied bronchoalveolar lavage (BAL) from patients admitted to ICUs with ventilator-associated pneumonia. BAL fluids were assessed with molecular tests, culture and blood culture. We successfully identified plant DNA in six patients out of 106 (6%) with ventilator-associated pneumonia. Inhalation was confirmed in four cases and suspected in the other two cases. Inhalation was significantly frequent in patients with plant DNA (four out of six patients) than those without plant DNA (three out of 100 patients) (P<0.001). Nicotiana tabacum chloroplast DNA was identified in three patients who were smokers (cases 2, 3 and 6). Cucurbita pepo, Morus bombycis and Triticum aestivum DNA were identified in cases 1, 4 and 5 respectively. Twenty-three different bacterial species, two viruses and five fungal species were identified from among these six patients by using molecular and culture techniques. Several of the pathogenic microorganisms identified are reported to be food-borne or tobacco plant-associated pathogens. CONCLUSIONS/SIGNIFICANCE: Our study shows that plants DNA may be identified in the BAL fluid of pneumonia patients, especially when exploring aspiration pneumonia, but the significance of the presence of plant DNA and its role in the pathogenesis of pneumonia is unknown and remains to be investigated. However, the identification of these plants may be a potential marker of aspiration in patients with pneumonia.",2010 Jun 24,"['Bousbia, Sabri', 'Papazian, Laurent', 'La Scola, Bernard', 'Raoult, Didier']",PLoS One,,,True
1054ed358dfede6e22877513169bef30c491c363,PMC,Class II Transactivator (CIITA) Enhances Cytoplasmic Processing of HIV-1 Pr55Gag,http://dx.doi.org/10.1371/journal.pone.0011304,PMC2892040,20585587,CC BY,"BACKGROUND: The Pr55(gag) (Gag) polyprotein of HIV serves as a scaffold for virion assembly and is thus essential for progeny virion budding and maturation. Gag localizes to the plasma membrane (PM) and membranes of late endosomes, allowing for release of infectious virus directly from the cell membrane and/or upon exocytosis. The host factors involved in Gag trafficking to these sites are largely unknown. Upon activation, CD4+ T cells, the primary target of HIV infection, express the class II transcriptional activator (CIITA) and therefore the MHC class II isotype, HLA-DR. Similar to Gag, HLA-DR localizes to the PM and at the membranes of endosomes and specialized vesicular MHC class II compartments (MIICs). In HIV producer cells, transient HLA-DR expression induces intracellular Gag accumulation and impairs virus release. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. However, neither of these phenomena is due to recapitulation of the class II antigen presentation pathway or CIITA-mediated transcriptional activation of virus genes. Interestingly, we demonstrate that CIITA, apart from its transcriptional effects, acts cytoplasmically to enhance Pr160(gag-pol) (Gag-Pol) levels and thereby the viral protease and Gag processing, accounting for the increased infectivity of virions from CIITA-expressing cells. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that CIITA enhances HIV Gag processing, and provides the first evidence of a novel, post-transcriptional, cytoplasmic function for a well-known transactivator.",2010 Jun 24,"['Porter, Kristen A.', 'Kelley, Lauren N.', 'George, Annette', 'Harton, Jonathan A.', 'Duus, Karen M.']",PLoS One,,,True
63c9d5537c05b45dde4b7584c66a95e839b582ff,PMC,A duplex real-time RT-PCR assay for detecting H5N1 avian influenza virus and pandemic H1N1 influenza virus,http://dx.doi.org/10.1186/1743-422X-7-113,PMC2892456,20515509,CC BY,"A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009) influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID(50 )(50% tissue culture infective dose) for H5N1 and 0.2 TCID(50 )for the pandemic H1N1, which was the same as that of each single-target RT-PCR for pandemic H1N1 and even more sensitive for H5N1 with the same primers and probes. No cross reactivity of detecting other subtype influenza viruses or respiratory tract viruses was observed. Two hundred and thirty-six clinical specimens were tested by comparing with single real-time RT-PCR and result from the duplex assay was 100% consistent with the results of single real-time RT-PCR and sequence analysis.",2010 Jun 2,"['Kang, Xiao-ping', 'Jiang, Tao', 'Li, Yong-qiang', 'Lin, Fang', 'Liu, Hong', 'Chang, Guo-hui', 'Zhu, Qing-yu', 'Qin, E-de', 'Qin, Cheng-feng', 'Yang, Yin-hui']",Virol J,,,True
18910856b917289b6bb3cc2cef0f78ff82ad4b02,PMC,The Impact of Matching Vaccine Strains and Post-SARS Public Health Efforts on Reducing Influenza-Associated Mortality among the Elderly,http://dx.doi.org/10.1371/journal.pone.0011317,PMC2892467,20592764,CC BY,"Public health administrators do not have effective models to predict excess influenza-associated mortality and monitor viral changes associated with it. This study evaluated the effect of matching/mismatching vaccine strains, type/subtype pattern changes in Taiwan's influenza viruses, and the impact of post-SARS (severe acute respiratory syndrome) public health efforts on excess influenza-associated mortalities among the elderly. A negative binomial model was developed to estimate Taiwan's monthly influenza-associated mortality among the elderly. We calculated three winter and annual excess influenza-associated mortalities [pneumonia and influenza (P&I), respiratory and circulatory, and all-cause] from the 1999–2000 through the 2006–2007 influenza seasons. Obtaining influenza virus sequences from the months/years in which death from P&I was excessive, we investigated molecular variation in vaccine-mismatched influenza viruses by comparing hemagglutinin 1 (HA1) of the circulating and vaccine strains. We found that the higher the isolation rate of A (H3N2) and vaccine-mismatched influenza viruses, the greater the monthly P&I mortality. However, this significant positive association became negative for higher matching of A (H3N2) and public health efforts with post-SARS effect. Mean excess P&I mortality for winters was significantly higher before 2003 than after that year [mean ± S.D.: 1.44±1.35 vs. 0.35±1.13, p = 0.04]. Further analysis revealed that vaccine-matched circulating influenza A viruses were significantly associated with lower excess P&I mortality during post-SARS winters (i.e., 2005–2007) than during pre-SARS winters [0.03±0.06 vs. 1.57±1.27, p = 0.01]. Stratification of these vaccine-matching and post-SARS effect showed substantial trends toward lower elderly excess P&I mortalities in winters with either mismatching vaccines during the post-SARS period or matching vaccines during the pre-SARS period. Importantly, all three excess mortalities were at their highest in May, 2003, when inter-hospital nosocomial infections were peaking. Furthermore, vaccine-mismatched H3N2 viruses circulating in the years with high excess P&I mortality exhibited both a lower amino acid identity percentage of HA1 between vaccine and circulating strains and a higher numbers of variations at epitope B. Our model can help future decision makers to estimate excess P&I mortality effectively, select and test virus strains for antigenic variation, and evaluate public health strategy effectiveness.",2010 Jun 25,"['Chan, Ta-Chien', 'Hsiao, Chuhsing Kate', 'Lee, Chang-Chun', 'Chiang, Po-Huang', 'Kao, Chuan-Liang', 'Liu, Chung-Ming', 'King, Chwan-Chuen']",PLoS One,,,True
17a5e67e3855ae5fa7d1a711f3249b6813c28386,PMC,"Insulin Degrading Enzyme Induces a Conformational Change in Varicella-Zoster Virus gE, and Enhances Virus Infectivity and Stability",http://dx.doi.org/10.1371/journal.pone.0011327,PMC2892511,20593027,CC0,"Varicella-zoster virus (VZV) glycoprotein E (gE) is essential for virus infectivity and binds to a cellular receptor, insulin-degrading enzyme (IDE), through its unique amino terminal extracellular domain. Previous work has shown IDE plays an important role in VZV infection and virus cell-to-cell spread, which is the sole route for VZV spread in vitro. Here we report that a recombinant soluble IDE (rIDE) enhances VZV infectivity at an early step of infection associated with an increase in virus internalization, and increases cell-to-cell spread. VZV mutants lacking the IDE binding domain of gE were impaired for syncytia formation and membrane fusion. Pre-treatment of cell-free VZV with rIDE markedly enhanced the stability of the virus over a range of conditions. rIDE interacted with gE to elicit a conformational change in gE and rendered it more susceptible to proteolysis. Co-incubation of rIDE with gE modified the size of gE. We propose that the conformational change in gE elicited by IDE enhances infectivity and stability of the virus and leads to increased fusogenicity during VZV infection. The ability of rIDE to enhance infectivity of cell-free VZV over a wide range of incubation times and temperatures suggests that rIDE may be useful for increasing the stability of varicella or zoster vaccines.",2010 Jun 25,"['Li, Qingxue', 'Ali, Mir A.', 'Wang, Kening', 'Sayre, Dean', 'Hamel, Frederick G.', 'Fischer, Elizabeth R.', 'Bennett, Robert G.', 'Cohen, Jeffrey I.']",PLoS One,,,True
5f1378b1fa0165baf6bd31d9e4d0d66d818a37c6,PMC,Aerosol influenza transmission risk contours: A study of humid tropics versus winter temperate zone,http://dx.doi.org/10.1186/1743-422X-7-98,PMC2893155,20470403,CC BY,"BACKGROUND: In recent years, much attention has been given to the spread of influenza around the world. With the continuing human outbreak of H5N1 beginning in 2003 and the H1N1 pandemic in 2009, focus on influenza and other respiratory viruses has been increased. It has been accepted for decades that international travel via jet aircraft is a major vector for global spread of influenza, and epidemiological differences between tropical and temperate regions observed. Thus we wanted to study how indoor environmental conditions (enclosed locations) in the tropics and winter temperate zones contribute to the aerosol spread of influenza by travelers. To this end, a survey consisting of 632 readings of temperature (T) versus relative humidity (RH) in 389 different enclosed locations air travelers are likely to visit in 8 tropical nations were compared to 102 such readings in 2 Australian cities, including ground transport, hotels, shops, offices and other publicly accessible locations, along with 586 time course readings from aircraft. RESULTS: An influenza transmission risk contour map was developed for T versus RH. Empirical equations were created for estimating: 1. risk relative to temperature and RH, and 2. time parameterized influenza transmission risk. Using the transmission risk contours and equations, transmission risk for each country's locations was compared with influenza reports from the countries. Higher risk enclosed locations in the tropics included new automobile transport, luxury buses, luxury hotels, and bank branches. Most temperate locations were high risk. CONCLUSION: Environmental control is recommended for public health mitigation focused on higher risk enclosed locations. Public health can make use of the methods developed to track potential vulnerability to aerosol influenza. The methods presented can also be used in influenza modeling. Accounting for differential aerosol transmission using T and RH can potentially explain anomalies of influenza epidemiology in addition to seasonality in temperate climates.",2010 May 14,"['Hanley, Brian P', 'Borup, Birthe']",Virol J,,,True
c24060d084e314b214e061995b5528b2e0071e31,PMC,CXCR2 Signaling Protects Oligodendrocytes and Restricts Demyelination in a Mouse Model of Viral-Induced Demyelination,http://dx.doi.org/10.1371/journal.pone.0011340,PMC2893165,20596532,CC BY,"BACKGROUND: The functional role of ELR-positive CXC chemokines during viral – induced demyelination was assessed. Inoculation of the neuroattenuated JHM strain of mouse hepatitis virus (JHMV) into the CNS of susceptible mice results in an acute encephalomyelitis that evolves into a chronic demyelinating disease, modeling white matter pathology observed in the human demyelinating disease Multiple Sclerosis. METHODOLOGY/PRINCIPAL FINDINGS: JHMV infection induced the rapid and sustained expression of transcripts specific for the ELR (+) chemokine ligands CXCL1 and CXCL2, as well as their binding receptor CXCR2, which was enriched within the spinal cord during chronic infection. Inhibiting CXCR2 signaling with neutralizing antiserum significantly (p<0.03) delayed clinical recovery. Moreover, CXCR2 neutralization was associated with an increase in the severity of demyelination that was independent of viral recrudescence or modulation of neuroinflammation. Rather, blocking CXCR2 was associated with increased numbers of apoptotic cells primarily within white matter tracts, suggesting that oligodendrocytes were affected. JHMV infection of enriched oligodendrocyte progenitor cell (OPC) cultures revealed that apoptosis was associated with elevated expression of cleaved caspase 3 and muted Bcl-2 expression. Inclusion of CXCL1 within JHMV infected cultures restricted caspase 3 cleavage and increased Bcl-2 expression that was associated with a significant (p<0.001) decrease in apoptosis. CXCR2 deficient oligodendrocytes were refractory to CXCL1 mediated protection from JHMV – induced apoptosis, readily activating caspase 3 and down regulating Bcl-2. CONCLUSION/SIGNIFICANCE: These findings highlight a previously unappreciated role for CXCR2 signaling in protecting oligodendrocyte lineage cells from apoptosis during inflammatory demyelination initiated by viral infection of the CNS.",2010 Jun 28,"['Hosking, Martin P.', 'Tirotta, Emanuele', 'Ransohoff, Richard M.', 'Lane, Thomas E.']",PLoS One,,,True
8126e29c1a00af5300f325021430faf4dfecbdc0,PMC,Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America,http://dx.doi.org/10.1371/journal.pone.0011341,PMC2893203,20596536,CC BY,"BACKGROUND: In mid-June 2009 the State of Victoria in Australia appeared to have the highest notification rate of pandemic (H1N1) 2009 influenza in the world. We hypothesise that this was because community transmission of pandemic influenza was already well established in Victoria at the time testing for the novel virus commenced. In contrast, this was not true for the pandemic in other parts of Australia, including Western Australia (WA). METHODS: We used data from detailed case follow-up of patients with confirmed infection in Victoria and WA to demonstrate the difference in the pandemic curve in two Australian states on opposite sides of the continent. We modelled the pandemic in both states, using a susceptible-infected-removed model with Bayesian inference accounting for imported cases. RESULTS: Epidemic transmission occurred earlier in Victoria and later in WA. Only 5% of the first 100 Victorian cases were not locally acquired and three of these were brothers in one family. By contrast, 53% of the first 102 cases in WA were associated with importation from Victoria. Using plausible model input data, estimation of the effective reproductive number for the Victorian epidemic required us to invoke an earlier date for commencement of transmission to explain the observed data. This was not required in modelling the epidemic in WA. CONCLUSION: Strong circumstantial evidence, supported by modelling, suggests community transmission of pandemic influenza was well established in Victoria, but not in WA, at the time testing for the novel virus commenced in Australia. The virus is likely to have entered Victoria and already become established around the time it was first identified in the US and Mexico.",2010 Jun 28,"['Kelly, Heath A.', 'Mercer, Geoff N.', 'Fielding, James E.', 'Dowse, Gary K.', 'Glass, Kathryn', 'Carcione, Dale', 'Grant, Kristina A.', 'Effler, Paul V.', 'Lester, Rosemary A.']",PLoS One,,,True
4a326f7b32461745b6e168b454a214839b704865,PMC,A Clathrin Independent Macropinocytosis-Like Entry Mechanism Used by Bluetongue Virus-1 during Infection of BHK Cells,http://dx.doi.org/10.1371/journal.pone.0011360,PMC2894058,20613878,CC BY,"Acid dependent infection of Hela and Vero cells by BTV-10 occurs from within early-endosomes following virus uptake by clathrin-mediated endocytosis (Forzan et al., 2007: J Virol 81: 4819–4827). Here we report that BTV-1 infection of BHK cells is also dependent on a low endosomal pH; however, virus entry and infection were not inhibited by dominant-negative mutants of Eps15, AP180 or the ‘aa’ splice variant of dynamin-2, which were shown to inhibit clathrin-mediated endocytosis. In addition, infection was not inhibited by depletion of cellular cholesterol, which suggests that virus entry is not mediated by a lipid-raft dependent process such as caveolae-mediated endocytosis. Although virus entry and infection were not inhibited by the dominant-negative dynamin-2 mutant, entry was inhibited by the general dynamin inhibitor, dynasore, indicating that virus entry is dynamin dependent. During entry, BTV-1 co-localised with LAMP-1 but not with transferrin, suggesting that virus is delivered to late-endosomal compartments without first passing through early-endosomes. BTV-1 entry and infection were inhibited by EIPA and cytochalasin-D, known macropinocytosis inhibitors, and during entry virus co-localised with dextran, a known marker for macropinocytosis/fluid-phase uptake. Our results extend earlier observations with BTV-10, and show that BTV-1 can infect BHK cells via an entry mechanism that is clathrin and cholesterol-independent, but requires dynamin, and shares certain characteristics in common with macropinocytosis.",2010 Jun 29,"['Gold, Sarah', 'Monaghan, Paul', 'Mertens, Peter', 'Jackson, Terry']",PLoS One,,,True
eaccbbd4d93f295b6c22ae217f159c288b29deb6,PMC,Understanding PRRSV Infection in Porcine Lung Based on Genome-Wide Transcriptome Response Identified by Deep Sequencing,http://dx.doi.org/10.1371/journal.pone.0011377,PMC2894071,20614006,CC BY,"Porcine reproductive and respiratory syndrome (PRRS) has been one of the most economically important diseases affecting swine industry worldwide and causes great economic losses each year. PRRS virus (PRRSV) replicates mainly in porcine alveolar macrophages (PAMs) and dendritic cells (DCs) and develops persistent infections, antibody-dependent enhancement (ADE), interstitial pneumonia and immunosuppression. But the molecular mechanisms of PRRSV infection still are poorly understood. Here we report on the first genome-wide host transcriptional responses to classical North American type PRRSV (N-PRRSV) strain CH 1a infection using Solexa/Illumina's digital gene expression (DGE) system, a tag-based high-throughput transcriptome sequencing method, and analyse systematically the relationship between pulmonary gene expression profiles after N-PRRSV infection and infection pathology. Our results suggest that N-PRRSV appeared to utilize multiple strategies for its replication and spread in infected pigs, including subverting host innate immune response, inducing an anti-apoptotic and anti-inflammatory state as well as developing ADE. Upregulation expression of virus-induced pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during N-PRRSV infection processes. N-PRRSV-induced immunosuppression might be mediated by apoptosis of infected cells, which caused depletion of immune cells and induced an anti-inflammatory cytokine response in which they were unable to eradicate the primary infection. Our systems analysis will benefit for better understanding the molecular pathogenesis of N-PRRSV infection, developing novel antiviral therapies and identifying genetic components for swine resistance/susceptibility to PRRS.",2010 Jun 29,"['Xiao, Shuqi', 'Jia, Jianyu', 'Mo, Delin', 'Wang, Qiwei', 'Qin, Limei', 'He, Zuyong', 'Zhao, Xiao', 'Huang, Yuankai', 'Li, Anning', 'Yu, Jingwei', 'Niu, Yuna', 'Liu, Xiaohong', 'Chen, Yaosheng']",PLoS One,,,True
3e339ee119ba0065cad4c40897cd1bc9dd0f118a,PMC,Interactions of SARS Coronavirus Nucleocapsid Protein with the host cell proteasome subunit p42,http://dx.doi.org/10.1186/1743-422X-7-99,PMC2894783,20478047,CC BY,"BACKGROUND: Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spreads rapidly and has a high case-mortality rate. The nucleocapsid protein (NP) of SARS-CoV may be critical for pathogenicity. This study sought to discover the host proteins that interact with SARS-CoV NP. RESULTS: Using surface plasmon resonance biomolecular interaction analysis (SPR/BIA) and matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry, we found that only the proteasome subunit p42 from human fetal lung diploid fibroblast (2BS) cells bound to SARS-CoV NP. This interaction was confirmed by the glutathione S-transferase (GST) fusion protein pulldown technique. The co-localization signal of SARS-CoV NP and proteasome subunit p42 in 2BS cells was detected using indirect immunofluorescence and confocal microscopy. p42 is a subunit of the 26S proteasome; this large, multi-protein complex is a component of the ubiquitin-proteasome pathway, which is involved in a variety of basic cellular processes and inflammatory responses. CONCLUSION: To our knowledge, this is the first report that SARS-CoV NP interacts with the proteasome subunit p42 within host cells. These data enhance our understanding of the molecular mechanisms of SARS-CoV pathogenicity and the means by which SARS-CoV interacts with host cells.",2010 May 17,"['Wang, Qin', 'Li, Chuan', 'Zhang, Quanfu', 'Wang, Tao', 'Li, Jiandong', 'Guan, Wuxiang', 'Yu, Jianshi', 'Liang, Mifang', 'Li, Dexin']",Virol J,,,True
f5133d66a71eb5add9881ec5f254fc0757a7ee06,PMC,A dynamic estimation of the daily cumulative cases during infectious disease surveillance: application to dengue fever,http://dx.doi.org/10.1186/1471-2334-10-136,PMC2894833,20504379,CC BY,"BACKGROUND: In infectious disease surveillance, when the laboratory confirmation of the cases is time-consuming, there is often a time lag between the number of suspect cases and the number of confirmed cases. This study proposes a dynamic statistical model to estimate the daily number of new cases and the daily cumulative number of infected cases, which was then applied to historic dengue fever data. METHODS: The duration between the date of disease onset and date of laboratory confirmation was assumed to follow a gamma distribution or a nonparametric distribution. A conditional probability of a case being a real case among the unconfirmed cases on a given date was then calculated. This probability along with the observed confirmed cases was integrated to estimate the daily number of new cases and the cumulative number of infected cases. RESULTS: The distribution of the onset-to-confirmation time for the positive cases was different from that of the negative cases. The daily new cases and cumulative epidemic curves estimated by the proposed method have a lower absolute relative bias than the values estimated solely based on the available daily-confirmed cases. CONCLUSION: The proposed method provides a more accurate real-time estimation of the daily new cases and daily cumulative number of infected cases. The model makes use of the most recent ""moving window"" of information relative to suspect cases and dynamically updates the parameters. The proposed method will be useful for the real-time evaluation of a disease outbreak when case classification requires a time-consuming laboratory process to identify a confirmed case.",2010 May 27,"['Chuang, Pei-Hung', 'Chuang, Jen-Hsiang', 'Lin, I-Feng']",BMC Infect Dis,,,True
bc7b2271acba0248f021e9e11cb91cec6358d924,PMC,Assessing the human immune system through blood transcriptomics,http://dx.doi.org/10.1186/1741-7007-8-84,PMC2895587,20619006,CC BY,Blood is the pipeline of the immune system. Assessing changes in transcript abundance in blood on a genome-wide scale affords a comprehensive view of the status of the immune system in health and disease. This review summarizes the work that has used this approach to identify therapeutic targets and biomarker signatures in the field of autoimmunity and infectious disease. Recent technological and methodological advances that will carry the blood transcriptome research field forward are also discussed.,2010 Jul 1,"['Chaussabel, Damien', 'Pascual, Virginia', 'Banchereau, Jacques']",BMC Biol,,,True
b5e924927b31aface620ada453f904e6e9ebb203,PMC,Bid Regulates the Pathogenesis of Neurotropic Reovirus,http://dx.doi.org/10.1371/journal.ppat.1000980,PMC2895667,20617182,CC BY,"Reovirus infection leads to apoptosis in both cultured cells and the murine central nervous system (CNS). NF-κB-driven transcription of proapoptotic cellular genes is required for the effector phase of the apoptotic response. Although both extrinsic death-receptor signaling pathways and intrinsic pathways involving mitochondrial injury are implicated in reovirus-induced apoptosis, mechanisms by which either of these pathways are activated and their relationship to NF-κB signaling following reovirus infection are unknown. The proapoptotic Bcl-2 family member, Bid, is activated by proteolytic cleavage following reovirus infection. To understand how reovirus integrates host signaling circuits to induce apoptosis, we examined proapoptotic signaling following infection of Bid-deficient cells. Although reovirus growth was not affected by the absence of Bid, cells lacking Bid failed to undergo apoptosis. Furthermore, we found that NF-κB activation is required for Bid cleavage and subsequent proapoptotic signaling. To examine the functional significance of Bid-dependent apoptosis in reovirus disease, we monitored fatal encephalitis caused by reovirus in the presence and absence of Bid. Survival of Bid-deficient mice was significantly enhanced in comparison to wild-type mice following either peroral or intracranial inoculation of reovirus. Decreased reovirus virulence in Bid-null mice was accompanied by a reduction in viral yield. These findings define a role for NF-κB-dependent cleavage of Bid in the cell death program initiated by viral infection and link Bid to viral virulence.",2010 Jul 1,"['Danthi, Pranav', 'Pruijssers, Andrea J.', 'Berger, Angela K.', 'Holm, Geoffrey H.', 'Zinkel, Sandra S.', 'Dermody, Terence S.']",PLoS Pathog,,,True
30fc9806c9b1ba0d786a31cad4a1d98b6642462d,PMC,Pandemic influenza preparedness and health systems challenges in Asia: results from rapid analyses in 6 Asian countries,http://dx.doi.org/10.1186/1471-2458-10-322,PMC2896940,20529345,CC BY,"BACKGROUND: Since 2003, Asia-Pacific, particularly Southeast Asia, has received substantial attention because of the anticipation that it could be the epicentre of the next pandemic. There has been active investment but earlier review of pandemic preparedness plans in the region reveals that the translation of these strategic plans into operational plans is still lacking in some countries particularly those with low resources. The objective of this study is to understand the pandemic preparedness programmes, the health systems context, and challenges and constraints specific to the six Asian countries namely Cambodia, Indonesia, Lao PDR, Taiwan, Thailand, and Viet Nam in the prepandemic phase before the start of H1N1/2009. METHODS: The study relied on the Systemic Rapid Assessment (SYSRA) toolkit, which evaluates priority disease programmes by taking into account the programmes, the general health system, and the wider socio-cultural and political context. The components under review were: external context; stewardship and organisational arrangements; financing, resource generation and allocation; healthcare provision; and information systems. Qualitative and quantitative data were collected in the second half of 2008 based on a review of published data and interviews with key informants, exploring past and current patterns of health programme and pandemic response. RESULTS: The study shows that health systems in the six countries varied in regard to the epidemiological context, health care financing, and health service provision patterns. For pandemic preparation, all six countries have developed national governance on pandemic preparedness as well as national pandemic influenza preparedness plans and Avian and Human Influenza (AHI) response plans. However, the governance arrangements and the nature of the plans differed. In the five developing countries, the focus was on surveillance and rapid containment of poultry related transmission while preparation for later pandemic stages was limited. The interfaces and linkages between health system contexts and pandemic preparedness programmes in these countries were explored. CONCLUSION: Health system context influences how the six countries have been preparing themselves for a pandemic. At the same time, investment in pandemic preparation in the six Asian countries has contributed to improvement in health system surveillance, laboratory capacity, monitoring and evaluation and public communications. A number of suggestions for improvement were presented to strengthen the pandemic preparation and mitigation as well as to overcome some of the underlying health system constraints.",2010 Jun 8,"['Hanvoravongchai, Piya', 'Adisasmito, Wiku', 'Chau, Pham Ngoc', 'Conseil, Alexandra', 'de Sa, Joia', 'Krumkamp, Ralf', 'Mounier-Jack, Sandra', 'Phommasack, Bounlay', 'Putthasri, Weerasak', 'Shih, Chin-Shui', 'Touch, Sok', 'Coker, Richard']",BMC Public Health,,,True
876ae65a682f1bf2941f54851442532ae722382c,PMC,Whole-proteome phylogeny of large dsDNA viruses and parvoviruses through a composition vector method related to dynamical language model,http://dx.doi.org/10.1186/1471-2148-10-192,PMC2898692,20565983,CC BY,"BACKGROUND: The vast sequence divergence among different virus groups has presented a great challenge to alignment-based analysis of virus phylogeny. Due to the problems caused by the uncertainty in alignment, existing tools for phylogenetic analysis based on multiple alignment could not be directly applied to the whole-genome comparison and phylogenomic studies of viruses. There has been a growing interest in alignment-free methods for phylogenetic analysis using complete genome data. Among the alignment-free methods, a dynamical language (DL) method proposed by our group has successfully been applied to the phylogenetic analysis of bacteria and chloroplast genomes. RESULTS: In this paper, the DL method is used to analyze the whole-proteome phylogeny of 124 large dsDNA viruses and 30 parvoviruses, two data sets with large difference in genome size. The trees from our analyses are in good agreement to the latest classification of large dsDNA viruses and parvoviruses by the International Committee on Taxonomy of Viruses (ICTV). CONCLUSIONS: The present method provides a new way for recovering the phylogeny of large dsDNA viruses and parvoviruses, and also some insights on the affiliation of a number of unclassified viruses. In comparison, some alignment-free methods such as the CV Tree method can be used for recovering the phylogeny of large dsDNA viruses, but they are not suitable for resolving the phylogeny of parvoviruses with a much smaller genome size.",2010 Jun 22,"['Yu, Zu-Guo', 'Chu, Ka Hou', 'Li, Chi Pang', 'Anh, Vo', 'Zhou, Li-Qian', 'Wang, Roger Wei']",BMC Evol Biol,,,True
9940375ae218bef442080efc4b430cf27323a4a6,PMC,Co-lethality studied as an asset against viral drug escape: the HIV protease case,http://dx.doi.org/10.1186/1745-6150-5-40,PMC2898770,20565756,CC BY,"BACKGROUND: Co-lethality, or synthetic lethality is the documented genetic situation where two, separately non-lethal mutations, become lethal when combined in one genome. Each mutation is called a ""synthetic lethal"" (SL) or a co-lethal. Like invariant positions, SL sets (SL linked couples) are choice targets for drug design against fast-escaping RNA viruses: mutational viral escape by loss of affinity to the drug may induce (synthetic) lethality. RESULTS: From an amino acid sequence alignment of the HIV protease, we detected the potential SL couples, potential SL sets, and invariant positions. From the 3D structure of the same protein we focused on the ones that were close to each other and accessible on the protein surface, to possibly bind putative drugs. We aligned 24,155 HIV protease amino acid sequences and identified 290 potential SL couples and 25 invariant positions. After applying the distance and accessibility filter, three candidate drug design targets of respectively 7 (under the flap), 4 (in the cantilever) and 5 (in the fulcrum) amino acid positions were found. CONCLUSIONS: These three replication-critical targets, located outside of the active site, are key to our anti-escape strategy. Indeed, biological evidence shows that 2/3 of those target positions perform essential biological functions. Their mutational variations to escape antiviral medication could be lethal, thus limiting the apparition of drug-resistant strains. REVIEWERS: This article was reviewed by Arcady Mushegian, Shamil Sunyaev and Claus Wilke.",2010 Jun 17,"['Brouillet, Sophie', 'Valere, Thomas', 'Ollivier, Emmanuelle', 'Marsan, Laurent', 'Vanet, Anne']",Biol Direct,,,True
31f9d7bce1db40d866a3e93b06ff9515c34fc3b7,PMC,Spatial patterns of Bovine Corona Virus and Bovine Respiratory Syncytial Virus in the Swedish beef cattle population,http://dx.doi.org/10.1186/1751-0147-52-33,PMC2898781,20492637,CC BY,"BACKGROUND: Both bovine coronavirus (BCV) and bovine respiratory syncytial virus (BRSV) infections are currently wide-spread in the Swedish dairy cattle population. Surveys of antibody levels in bulk tank milk have shown very high nationwide prevalences of both BCV and BRSV, with large variations between regions. In the Swedish beef cattle population however, no investigations have yet been performed regarding the prevalence and geographical distribution of BCV and BRSV. A cross-sectional serological survey for BCV and BRSV was carried out in Swedish beef cattle to explore any geographical patterns of these infections. METHODS: Blood samples were collected from 2,763 animals located in 2,137 herds and analyzed for presence of antibodies to BCV and BRSV. Moran's I was calculated to assess spatial autocorrelation, and identification of geographical cluster was performed using spatial scan statistics. RESULTS: Animals detected positive to BCV or BRSV were predominately located in the central-western and some southern parts of Sweden. Moran's I indicated global spatial autocorrelation. BCV and BRSV appeared to be spatially related: two areas in southern Sweden (Skaraborg and Skåne) had a significantly higher prevalence of BCV (72.5 and 65.5% respectively); almost the same two areas were identified as being high-prevalence clusters for BRSV (69.2 and 66.8% respectively). An area in south-east Sweden (Kronoberg-Blekinge) had lower prevalences for both infections than expected (23.8 and 20.7% for BCV and BRSV respectively). Another area in middle-west Sweden (Värmland-Dalarna) had also a lower prevalence for BRSV (7.9%). Areas with beef herd density > 10 per 100 km(2 )were found to be at significantly higher risk of being part of high-prevalence clusters. CONCLUSION: These results form a basis for further investigations of between-herds dynamics and risk factors for these infections in order to design effective control strategies.",2010 May 21,"['Beaudeau, Francois', 'Björkman, Camilla', 'Alenius, Stefan', 'Frössling, Jenny']",Acta Vet Scand,,,True
2183478af3f9343c0f566eee8b5d95a1abea6754,PMC,The First Human Epitope Map of the Alphaviral E1 and E2 Proteins Reveals a New E2 Epitope with Significant Virus Neutralizing Activity,http://dx.doi.org/10.1371/journal.pntd.0000739,PMC2903468,20644615,CC0,"BACKGROUND: Venezuelan equine encephalitis virus (VEEV) is responsible for VEE epidemics that occur in South and Central America and the U.S. The VEEV envelope contains two glycoproteins E1 (mediates cell membrane fusion) and E2 (binds receptor and elicits virus neutralizing antibodies). Previously we constructed E1 and E2 epitope maps using murine monoclonal antibodies (mMAbs). Six E2 epitopes (E2(c,d,e,f,g,h)) bound VEEV-neutralizing antibody and mapped to amino acids (aa) 182–207. Nothing is known about the human antibody repertoire to VEEV or epitopes that engage human virus-neutralizing antibodies. There is no specific treatment for VEE; however virus-neutralizing mMAbs are potent protective and therapeutic agents for mice challenged with VEEV by either peripheral or aerosol routes. Therefore, fully human MAbs (hMAbs) with virus-neutralizing activity should be useful for prevention or clinical treatment of human VEE. METHODS: We used phage-display to isolate VEEV-specific hFabs from human bone marrow donors. These hFabs were characterized by sequencing, specificity testing, VEEV subtype cross-reactivity using indirect ELISA, and in vitro virus neutralization capacity. One E2-specific neutralizing hFAb, F5n, was converted into IgG, and its binding site was identified using competitive ELISA with mMAbs and by preparing and sequencing antibody neutralization-escape variants. FINDINGS: Using 11 VEEV-reactive hFabs we constructed the first human epitope map for the alphaviral surface proteins E1 and E2. We identified an important neutralization-associated epitope unique to the human immune response, E2 aa115–119. Using a 9 Å resolution cryo-electron microscopy map of the Sindbis virus E2 protein, we showed the probable surface location of this human VEEV epitope. CONCLUSIONS: The VEEV-neutralizing capacity of the hMAb F5 nIgG is similar to that exhibited by the humanized mMAb Hy4 IgG. The Hy4 IgG has been shown to limit VEEV infection in mice both prophylactically and therapeutically. Administration of a cocktail of F5n and Hy4 IgGs, which bind to different E2 epitopes, could provide enhanced prophylaxis or immunotherapy for VEEV, while reducing the possibility of generating possibly harmful virus neutralization-escape variants in vivo.",2010 Jul 13,"['Hunt, Ann R.', 'Frederickson, Shana', 'Maruyama, Toshiaki', 'Roehrig, John T.', 'Blair, Carol D.']",PLoS Negl Trop Dis,,,True
b29aec7c51b6c428e566fa6e092797fc4da21b29,PMC,The Battle between Virus and Host: Modulation of Toll-Like Receptor Signaling Pathways by Virus Infection,http://dx.doi.org/10.1155/2010/184328,PMC2903949,20672047,CC BY,"In order to establish an infection, viruses need to either suppress or escape from host immune defense systems. Recent immunological research has focused on innate immunity as the first line of host defense, especially pattern recognition molecules such as Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and NOD-like receptors (NLRs). Various microbial components are recognized by their vague and common molecular shapes so-called, pathogen-associated molecular patterns (PAMPs). PAMPs induce inflammatory reactions mediated by the activation of the transcription factor, NF-κB, and by interferons, which lead to an antiviral immune response. Viruses have the capacity to suppress or escape from this pattern recognition molecule-mediated antimicrobial response in various ways. In this paper, we review the various strategies used by viruses to modulate the pattern recognition molecule-mediated innate immune response.",2010 Jun 16,"['Yokota, Shin-ichi', 'Okabayashi, Tamaki', 'Fujii, Nobuhiro']",Mediators Inflamm,,,True
6af49373c566eac05d2609e3474e847157cafb3b,PMC,Proteomic analysis of primary duck hepatocytes infected with duck hepatitis B virus,http://dx.doi.org/10.1186/1477-5956-8-28,PMC2904733,20529248,CC BY,"BACKGROUND: Hepatitis B virus (HBV) is a major cause of liver infection in human. Because of the lack of an appropriate cell culture system for supporting HBV infection efficiently, the cellular and molecular mechanisms of hepadnavirus infection remain incompletely understood. Duck heptatitis B virus (DHBV) can naturally infect primary duck hepatocytes (PDHs) that provide valuable model systems for studying hepadnavirus infection in vitro. In this report, we explored global changes in cellular protein expression in DHBV infected PDHs by two-dimension gel electrophoresis (2-DE) combined with MALDI-TOF/TOF tandem mass spectrometry (MS/MS). RESULTS: The effects of hepadnavirus infection on hepatocytes were investigated in DHBV infected PDHs by the 2-DE analysis. Proteomic profile of PDHs infected with DHBV were analyzed at 24, 72 and 120 h post-infection by comparing with uninfected PDHs, and 75 differentially expressed protein spots were revealed by 2-DE analysis. Among the selected protein spots, 51 spots were identified corresponding to 42 proteins by MS/MS analysis; most of them were matched to orthologous proteins of Gallus gallus, Anas platyrhynchos or other avian species, including alpha-enolase, lamin A, aconitase 2, cofilin-2 and annexin A2, etc. The down-regulated expression of beta-actin and annexin A2 was confirmed by Western blot analysis, and potential roles of some differentially expressed proteins in the virus-infected cells have been discussed. CONCLUSIONS: Differentially expressed proteins of DHBV infected PDHs revealed by 2-DE, are involved in carbohydrate metabolism, amino acid metabolism, stress responses and cytoskeleton processes etc, providing the insight to understanding of interactions between hepadnavirus and hepatocytes and molecular mechanisms of hepadnavirus pathogenesis.",2010 Jun 7,"['Zhao, Yanfeng', 'Ben, Haijing', 'Qu, Su', 'Zhou, Xinwen', 'Yan, Liang', 'Xu, Bin', 'Zhou, Shuangcheng', 'Lou, Qiang', 'Ye, Rong', 'Zhou, Tianlun', 'Yang, Pengyuan', 'Qu, Di']",Proteome Sci,,,True
7ce8b2a6ee1373cf063fa46c1cdc81151babc7e1,PMC,The identification of unique serum proteins of HIV-1 latently infected long-term non-progressor patients,http://dx.doi.org/10.1186/1742-6405-7-21,PMC2908552,20604950,CC BY,"BACKGROUND: The search for disease biomarkers within human peripheral fluids has become a favorable approach to preventative therapeutics throughout the past few years. The comparison of normal versus disease states can identify an overexpression or a suppression of critical proteins where illness has directly altered a patient's cellular homeostasis. In particular, the analysis of HIV-1 infected serum is an attractive medium with which to identify altered protein expression due to the ease and non-invasive methods of collecting samples as well as the corresponding insight into the in vivo interaction of the virus with infected cells/tissue. The utilization of proteomic techniques to globally identify differentially expressed serum proteins in response to HIV-1 infection is a significant undertaking that is complicated due to the innate protein profile of human serum. RESULTS: Here, the depletion of 12 of the most abundant serum proteins, followed by two-dimensional gel electrophoresis coupled with identification of these proteins using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, has allowed for the identification of differentially expressed, low abundant serum proteins. We have analyzed and compared serum samples from HIV-1 infected subjects who are being treated using highly active antiretroviral therapy (HAART) to those who are latently infected but have not progressed to AIDS despite the absence of treatment, i.e. long term non-progressors (LTNPs). Here we have identified unique serum proteins that are differentially expressed in LTNP HIV-1 patients and may contribute to the ability of these patients to combat HIV-1 infection in the absence of HAART. We focused on the cdk4/6 cell cycle inhibitor p16(INK4A )and found that the treatment of HIV-1 latently infected cell lines with p16(INK4A )decreases viral production despite it not being expressed endogenously in these cells. CONCLUSIONS: Identification of these unique proteins may serve as an indication of altered viral states in response to infection as well as a natural phenotypic variability in response to HIV-1 infection in a given population.",2010 Jul 6,"['Van Duyne, Rachel', 'Guendel, Irene', 'Kehn-Hall, Kylene', 'Easley, Rebecca', 'Klase, Zachary', 'Liu, Chenglong', 'Young, Mary', 'Kashanchi, Fatah']",AIDS Res Ther,,,True
00cf719db65d07c0c7bdea9defaea448fc5f5786,PMC,A Systems Immunology Approach to Plasmacytoid Dendritic Cell Function in Cytopathic Virus Infections,http://dx.doi.org/10.1371/journal.ppat.1001017,PMC2908624,20661432,CC BY,"Plasmacytoid dendritic cell (pDC)-mediated protection against cytopathic virus infection involves various molecular, cellular, tissue-scale, and organism-scale events. In order to better understand such multiscale interactions, we have implemented a systems immunology approach focusing on the analysis of the structure, dynamics and operating principles of virus-host interactions which constrain the initial spread of the pathogen. Using high-resolution experimental data sets coming from the well-described mouse hepatitis virus (MHV) model, we first calibrated basic modules including MHV infection of its primary target cells, i.e. pDCs and macrophages (Mφs). These basic building blocks were used to generate and validate an integrative mathematical model for in vivo infection dynamics. Parameter estimation for the system indicated that on a per capita basis, one infected pDC secretes sufficient type I IFN to protect 10(3) to 10(4) Mφs from cytopathic viral infection. This extremely high protective capacity of pDCs secures the spleen's capability to function as a ‘sink’ for the virus produced in peripheral organs such as the liver. Furthermore, our results suggest that the pDC population in spleen ensures a robust protection against virus variants which substantially down-modulate IFN secretion. However, the ability of pDCs to protect against severe disease caused by virus variants exhibiting an enhanced liver tropism and higher replication rates appears to be rather limited. Taken together, this systems immunology analysis suggests that antiviral therapy against cytopathic viruses should primarily limit viral replication within peripheral target organs.",2010 Jul 22,"['Bocharov, Gennady', 'Züst, Roland', 'Cervantes-Barragan, Luisa', 'Luzyanina, Tatyana', 'Chiglintsev, Egor', 'Chereshnev, Valery A.', 'Thiel, Volker', 'Ludewig, Burkhard']",PLoS Pathog,,,True
448c6dce11a897a8baa0815f46a77307b16049db,PMC,Nonparametric methods for the analysis of single-color pathogen microarrays,http://dx.doi.org/10.1186/1471-2105-11-354,PMC2909221,20584331,CC BY,"BACKGROUND: The analysis of oligonucleotide microarray data in pathogen surveillance and discovery is a challenging task. Target template concentration, nucleic acid integrity, and host nucleic acid composition can each have a profound effect on signal distribution. Exploratory analysis of fluorescent signal distribution in clinical samples has revealed deviations from normality, suggesting that distribution-free approaches should be applied. RESULTS: Positive predictive value and false positive rates were examined to assess the utility of three well-established nonparametric methods for the analysis of viral array hybridization data: (1) Mann-Whitney U, (2) the Spearman correlation coefficient and (3) the chi-square test. Of the three tests, the chi-square proved most useful. CONCLUSIONS: The acceptance of microarray use for routine clinical diagnostics will require that the technology be accompanied by simple yet reliable analytic methods. We report that our implementation of the chi-square test yielded a combination of low false positive rates and a high degree of predictive accuracy.",2010 Jun 28,"['Jabado, Omar J', 'Conlan, Sean', 'Quan, Phenix-Lan', 'Hui, Jeffrey', 'Palacios, Gustavo', 'Hornig, Mady', 'Briese, Thomas', 'Lipkin, W Ian']",BMC Bioinformatics,,,True
99a643136f67ee7f56c5abdea714a2a2ca89c10e,PMC,"Pneumonia Incidence and Mortality in Mainland China: Systematic Review of Chinese and English Literature, 1985–2008",http://dx.doi.org/10.1371/journal.pone.0011721,PMC2909231,20668535,CC0,"BACKGROUND: Pneumonia is a leading infectious disease killer worldwide, yet the burden in China is not well understood as much of the data is published in the non-English literature. METHODOLOGY/PRINCIPAL FINDINGS: We systematically reviewed the Chinese- and English-language literature for studies with primary data on pneumonia incidence and mortality in mainland China. Between 1985 and 2008, 37 studies met the inclusion criteria. The quality of the studies was highly variable. For children <5 years, incidence ranged from 0.06–0.27 episodes per person-year and mortality ranged from 184–1,223 deaths per 100,000 population. Overall incidence and mortality were stable or decreased over the study period and were higher in rural compared to urban areas. CONCLUSIONS/SIGNIFICANCE: Pneumonia continues to be a major public health challenge in young children in China, and estimates of pneumonia incidence and mortality vary widely. Reliable surveillance data and new prevention efforts may be needed to achieve and document additional declines, especially in areas with higher incidence and mortality such as rural settings.",2010 Jul 23,"['Guan, Xuhua', 'Silk, Benjamin J.', 'Li, Wenkai', 'Fleischauer, Aaron T.', 'Xing, Xuesen', 'Jiang, Xiaoqing', 'Yu, Hongjie', 'Olsen, Sonja J.', 'Cohen, Adam L.']",PLoS One,,,True
a3778f543ef74ff3a0dd90250221b77ee38d7533,PMC,Inverse folding of RNA pseudoknot structures,http://dx.doi.org/10.1186/1748-7188-5-27,PMC2909241,20573197,CC BY,"BACKGROUND: RNA exhibits a variety of structural configurations. Here we consider a structure to be tantamount to the noncrossing Watson-Crick and G-U-base pairings (secondary structure) and additional cross-serial base pairs. These interactions are called pseudoknots and are observed across the whole spectrum of RNA functionalities. In the context of studying natural RNA structures, searching for new ribozymes and designing artificial RNA, it is of interest to find RNA sequences folding into a specific structure and to analyze their induced neutral networks. Since the established inverse folding algorithms, RNAinverse, RNA-SSD as well as INFO-RNA are limited to RNA secondary structures, we present in this paper the inverse folding algorithm Inv which can deal with 3-noncrossing, canonical pseudoknot structures. RESULTS: In this paper we present the inverse folding algorithm Inv. We give a detailed analysis of Inv, including pseudocodes. We show that Inv allows to design in particular 3-noncrossing nonplanar RNA pseudoknot 3-noncrossing RNA structures-a class which is difficult to construct via dynamic programming routines. Inv is freely available at http://www.combinatorics.cn/cbpc/inv.html. CONCLUSIONS: The algorithm Inv extends inverse folding capabilities to RNA pseudoknot structures. In comparison with RNAinverse it uses new ideas, for instance by considering sets of competing structures. As a result, Inv is not only able to find novel sequences even for RNA secondary structures, it does so in the context of competing structures that potentially exhibit cross-serial interactions.",2010 Jun 23,"['Gao, James ZM', 'Li, Linda YM', 'Reidys, Christian M']",Algorithms Mol Biol,,,True
8d1543ffb6bf876bc0a8fb927068f6f3c6938497,PMC,Proteomic analysis of purified coronavirus infectious bronchitis virus particles,http://dx.doi.org/10.1186/1477-5956-8-29,PMC2909931,20534109,CC BY,"BACKGROUND: Infectious bronchitis virus (IBV) is the coronavirus of domestic chickens causing major economic losses to the poultry industry. Because of the complexity of the IBV life cycle and the small number of viral structural proteins, important virus-host relationships likely remain to be discovered. Toward this goal, we performed two-dimensional gel electrophoresis fractionation coupled to mass spectrometry identification approaches to perform a comprehensive proteomic analysis of purified IBV particles. RESULTS: Apart from the virus-encoded structural proteins, we detected 60 host proteins in the purified virions which can be grouped into several functional categories including intracellular trafficking proteins (20%), molecular chaperone (18%), macromolcular biosynthesis proteins (17%), cytoskeletal proteins (15%), signal transport proteins (15%), protein degradation (8%), chromosome associated proteins (2%), ribosomal proteins (2%), and other function proteins (3%). Interestingly, 21 of the total host proteins have not been reported to be present in virions of other virus families, such as major vault protein, TENP protein, ovalbumin, and scavenger receptor protein. Following identification of the host proteins by proteomic methods, the presence of 4 proteins in the purified IBV preparation was verified by western blotting and immunogold labeling detection. CONCLUSIONS: The results present the first standard proteomic profile of IBV and may facilitate the understanding of the pathogenic mechanisms.",2010 Jun 9,"['Kong, Qingming', 'Xue, Chunyi', 'Ren, Xiangpeng', 'Zhang, Chengwen', 'Li, Linlin', 'Shu, Dingming', 'Bi, Yingzuo', 'Cao, Yongchang']",Proteome Sci,,,True
964442dc964b2d97ceef1883ce2353e866efd8c2,PMC,Difference of clinical features in childhood Mycoplasma pneumoniae pneumonia,http://dx.doi.org/10.1186/1471-2431-10-48,PMC2910686,20604923,CC BY,"BACKGROUND: M. pneumoniae pneumonia (MP) has been reported in 10-40% of community-acquired pneumonia cases. We aimed to evaluate the difference of clinical features in children with MP, according to their age and chest radiographic patterns. METHODS: The diagnosis of MP was made by examinations at both admission and discharge and by two serologic tests: the indirect microparticle agglutinin assay (≥1:40) and the cold agglutinins titer (≥1:32). A total of 191 children with MP were grouped by age: ≤2 years of age (29 patients), 3-5 years of age (81 patients), and ≥6 years of age (81 patients). They were also grouped by pneumonia pattern: bronchopneumonia group (96 patients) and segmental/lobar pneumonia group (95 patients). RESULTS: Eighty-six patients (45%) were seroconverters, and the others showed increased antibody titers during hospitalization. Among the three age groups, the oldest children showed the longest duration of fever, highest C-reactive protein (CRP) values, and the most severe pneumonia pattern. The patients with segmental/lobar pneumonia were older and had longer fever duration and lower white blood cell (WBC) and lymphocyte counts, compared with those with bronchopneumonia. The patient group with the most severe pulmonary lesions had the most prolonged fever, highest CRP, highest rate of seroconverters, and lowest lymphocyte counts. Thrombocytosis was observed in 8% of patients at admission, but in 33% of patients at discharge. CONCLUSIONS: In MP, older children had more prolonged fever and more severe pulmonary lesions. The severity of pulmonary lesions was associated with the absence of diagnostic IgM antibodies at presentation and lymphocyte count. Short-term paired IgM serologic test may be mandatory for early and definitive diagnosis of MP.",2010 Jul 6,"['Youn, You-Sook', 'Lee, Kyung-Yil', 'Hwang, Ja-Young', 'Rhim, Jung-Woo', 'Kang, Jin-Han', 'Lee, Joon-Sung', 'Kim, Ji-Chang']",BMC Pediatr,,,True
fac2afdb0450de6c766a24baf26e3ce6e03e09e2,PMC,HIV Antigen Incorporation within Adenovirus Hexon Hypervariable 2 for a Novel HIV Vaccine Approach,http://dx.doi.org/10.1371/journal.pone.0011815,PMC2910733,20676400,CC BY,"Adenoviral (Ad) vectors have been used for a variety of vaccine applications including cancer and infectious diseases. Traditionally, Ad-based vaccines are designed to express antigens through transgene expression of a given antigen. However, in some cases these conventional Ad-based vaccines have had sub-optimal clinical results. These sub-optimal results are attributed in part to pre-existing Ad serotype 5 (Ad5) immunity. In order to circumvent the need for antigen expression via transgene incorporation, the “antigen capsid-incorporation” strategy has been developed and used for Ad-based vaccine development in the context of a few diseases. This strategy embodies the incorporation of antigenic peptides within the capsid structure of viral vectors. The major capsid protein hexon has been utilized for these capsid incorporation strategies due to hexon's natural role in the generation of anti-Ad immune response and its numerical representation within the Ad virion. Using this strategy, we have developed the means to incorporate heterologous peptide epitopes specifically within the major surface-exposed domains of the Ad capsid protein hexon. Our study herein focuses on generation of multivalent vaccine vectors presenting HIV antigens within the Ad capsid protein hexon, as well as expressing an HIV antigen as a transgene. These novel vectors utilize HVR2 as an incorporation site for a twenty-four amino acid region of the HIV membrane proximal ectodomain region (MPER), derived from HIV glycoprotein gp41 (gp41). Our study herein illustrates that our multivalent anti-HIV vectors elicit a cellular anti-HIV response. Furthermore, vaccinations with these vectors, which present HIV antigens at HVR2, elicit a HIV epitope-specific humoral immune response.",2010 Jul 27,"['Matthews, Qiana L.', 'Fatima, Aiman', 'Tang, Yizhe', 'Perry, Brian A.', 'Tsuruta, Yuko', 'Komarova, Svetlana', 'Timares, Laura', 'Zhao, Chunxia', 'Makarova, Natalia', 'Borovjagin, Anton V.', 'Stewart, Phoebe L.', 'Wu, Hongju', 'Blackwell, Jerry L.', 'Curiel, David T.']",PLoS One,,,True
3bf0902346541d9c58458ab14fc97d2f95e2f63d,PMC,Coping flexibility in college students with depressive symptoms,http://dx.doi.org/10.1186/1477-7525-8-66,PMC2911409,20626865,CC BY,"BACKGROUND: The current study explored the prevalence of depressed mood among Chinese undergraduate students and examined the coping patterns and degree of flexibility of flexibility of such patterns associated with such mood. METHODS: A set of questionnaire assessing coping patterns, coping flexibility, and depressive symptoms were administered to 428 students (234 men and 194 women). RESULTS: A total of 266 participants both completed the entire set of questionnaires and reported a frequency of two or more stressful life events (the criterion needed to calculate variance in perceived controllability). Findings showed that higher levels of depressive symptoms were significantly associated with higher levels of both event frequency (r = .368, p < .001) and event impact (r = .245, p < .001) and lower levels of perceived controllability (r = -.261, p < .001), coping effectiveness (r = -.375, p < .001), and ratio of strategy to situation fit (r = -.108, p < .05). Depressive symptoms were not significantly associated with cognitive flexibility (variance of perceived controllability; r = .031, p = .527), Gender was not a significant moderator of any of the reported associations. CONCLUSIONS: Findings indicate that Chinese university students with depressive symptoms reported experiencing a greater number of negative events than did non-depressed university students. In addition, undergraduates with depressive symptoms were more likely than other undergraduates to utilize maladaptive coping methods. Such findings highlight the potential importance of interventions aimed at helping undergraduate students with a lower coping flexibility develop skills to cope with stressful life events.",2010 Jul 13,"['Zong, Ji-Gang', 'Cao, Xiao-Yan', 'Cao, Yuan', 'Shi, Yan-Fang', 'Wang, Yu-Na', 'Yan, Chao', 'Abela, John RZ', 'Gan, Yi-Qun', 'Gong, Qi-Yong', 'Chan, Raymond CK']",Health Qual Life Outcomes,,,True
284b00ca025a939e64aefb5129b9e942c065baaf,PMC,Vaccination with attenuated Salmonella enterica Dublin expressing E coli O157:H7 outer membrane protein Intimin induces transient reduction of fecal shedding of E coli O157:H7 in cattle,http://dx.doi.org/10.1186/1746-6148-6-35,PMC2912257,20609252,CC BY,"BACKGROUND: Escherichia coli serogroup O157:H7 has emerged as an important zoonotic bacterial pathogen, causing a range of symptoms from self-limiting bloody diarrhea to severe hemorrhagic colitis and hemolytic-uremic syndrome in humans. Beef and dairy cattle are considered the most important animal reservoirs for this pathogen. One of the important virulence characteristics of E. coli O157:H7 is the eaeA gene encoding the 97 kDa surface protein intimin. Intimin is required for attachment and effacement during the interaction of enterohemorrhagic E. coli with human and bovine neonatal enterocytes. The present study was undertaken to test the hypothesis that an adaptive mucosal immune response directed against intimin will reduce or prevent enteric colonization and fecal shedding of E. coli O157:H7 in cattle. RESULTS: Cattle were orally inoculated with either milk (control), milk with live attenuated Salmonella enterica serovar Dublin (vector), or milk with live attenuated recombinant S. Dublin expressing intimin (vaccinated) on days 0, 14 and 28. On day 98, all calves were challenged orally with E. coli O157:H7 to evaluate whether vaccination with the recombinant S. Dublin expressing intimin would reduce the level of E. coli O157:H7 fecal shedding. During the first 28 days, vaccinated calves shed both the vector strain and the intimin-expressing S. Dublin strain at a similar level. The vector strain was shed for a significantly longer period as compared to the level of recombinant vaccine strain. Calves that received the intimin-expressed vaccine ceased shedding S. Dublin from day 28 to day 63. All calves were challenged with E. coli O157:H7 on day 98 to determine the effect on fecal shedding of E. coli O157:H7. The amount of E. coli O157:H7 in feces was measured for 30 days post-challenge. We observed a transient clearance of E. coli O157:H7 from the feces in the vaccinated calves. The magnitude of fecal E. coli O157:H7 shedding did not correlate with the presence of intimin-specific fecal IgA. CONCLUSION: Oral vaccination with live attenuated recombinant S. Dublin expressing intimin reduced enteric colonization and fecal shedding of E. coli O157:H7. However, the transient clearance of E. coli O157:H7 was not associated with an enhanced IgA-mediated mucosal immune response.",2010 Jul 7,"['Khare, Sangeeta', 'Alali, Walid', 'Zhang, Shuping', 'Hunter, Doris', 'Pugh, Roberta', 'Fang, Ferric C', 'Libby, Stephen J', 'Adams, L Garry']",BMC Vet Res,,,True
8cd344d423cfae8a07936b58eb1e172fa62bcc5d,PMC,The Role of Chemokines during Viral Infection of the CNS,http://dx.doi.org/10.1371/journal.ppat.1000937,PMC2912390,20686655,CC BY,,2010 Jul 29,"['Hosking, Martin P.', 'Lane, Thomas E.']",PLoS Pathog,,,True
fa47af75688fa3fab2afde5ed3f1a7fdd9624746,PMC,Lessons from SARS: A retrospective study of outpatient care during an infectious disease outbreak,http://dx.doi.org/10.1186/1471-2431-10-51,PMC2914048,20646293,CC BY,"BACKGROUND: During severe acute respiratory syndrome (SARS) outbreak in Toronto, outpatient clinics at SickKids Hospital were closed to prevent further disease transmission. In response, a decision was made by the neonatal neuro-developmental follow up (NNFU) clinic staff to select patients with scheduled appointments to have a mail/telephone assessment using Ages and Stages Questionnaire (ASQ) or to postpone/skip their visit. The objective of this study was to compare the developmental assessment and its outcome in two groups of NNFU clinic patients, SARS versus non-SARS, over three standard clinic appointments. METHODS: We compared the diagnostic accuracy (identification of developmental delay), and patient management (referral for therapy or communication of a new diagnosis) of the strategies used during SARS, April/May 2003, to the standard assessment methods used for patients seen in April/May 2005 (non-SARS). In all cases data were obtained for 3 patient visits: before, during and after these 2 months and were compared using descriptive statistics. RESULTS: There were 95 patients in the SARS group and 99 non-SARS patients. The gestational age, sex, entry diagnosis and age at the clinic visit was not different between the groups. The NNFU clinic staff mailed ASQ to 27 families during SARS, 17 (63%) were returned, and 8 of the 17 were then contacted by telephone. Criteria used to identify infants at risk selected for either mailed ASQ or phone interviews were not clearly defined in the patients' charts. There was a significant under identification of developmental delay during SARS (18% versus 45%). Of those who responded to the mailed questionnaire, referrals for therapy rates were similar to non-SARS group. The lost to follow up rate was 24% for the SARS group compared with 7% for non-SARS. There was no difference in the overall rate of developmental delay in the two groups as identified at the 'after' visit. CONCLUSIONS: Poor advanced planning led to a haphazard assessment of patients during this infectious disease outbreak. Future pandemic plans should consider planning for outpatient care as well as in hospital management of patients.",2010 Jul 20,"['Nasef, Nehad', ""O'Brien, Karel"", 'Wylie, Lesley', 'Unger, Sharon']",BMC Pediatr,,,True
08174b668145c88e0e719dac2a03b30fb68f5de5,PMC,Serodiagnosis of Echinococcus spp. Infection: Explorative Selection of Diagnostic Antigens by Peptide Microarray,http://dx.doi.org/10.1371/journal.pntd.0000771,PMC2914747,20689813,CC BY,"BACKGROUND: Production of native antigens for serodiagnosis of helminthic infections is laborious and hampered by batch-to-batch variation. For serodiagnosis of echinococcosis, especially cystic disease, most screening tests rely on crude or purified Echinococcus granulosus hydatid cyst fluid. To resolve limitations associated with native antigens in serological tests, the use of standardized and highly pure antigens produced by chemical synthesis offers considerable advantages, provided appropriate diagnostic sensitivity and specificity is achieved. METHODOLOGY/PRINCIPAL FINDINGS: Making use of the growing collection of genomic and proteomic data, we applied a set of bioinformatic selection criteria to a collection of protein sequences including conceptually translated nucleotide sequence data of two related tapeworms, Echinococcus multilocularis and Echinococcus granulosus. Our approach targeted alpha-helical coiled-coils and intrinsically unstructured regions of parasite proteins potentially exposed to the host immune system. From 6 proteins of E. multilocularis and 5 proteins of E. granulosus, 45 peptides between 24 and 30 amino acids in length were designed. These peptides were chemically synthesized, spotted on microarrays and screened for reactivity with sera from infected humans. Peptides reacting above the cut-off were validated in enzyme-linked immunosorbent assays (ELISA). Peptides identified failed to differentiate between E. multilocularis and E. granulosus infection. The peptide performing best reached 57% sensitivity and 94% specificity. This candidate derived from Echinococcus multilocularis antigen B8/1 and showed strong reactivity to sera from patients infected either with E. multilocularis or E. granulosus. CONCLUSIONS/SIGNIFICANCE: This study provides proof of principle for the discovery of diagnostically relevant peptides by bioinformatic selection complemented with screening on a high-throughput microarray platform. Our data showed that a single peptide cannot provide sufficient diagnostic sensitivity whereas pooling several peptide antigens improved sensitivity; thus combinations of several peptides may lead the way to new diagnostic tests that replace, or at least complement conventional immunodiagnosis of echinococcosis. Our strategy could prove useful for diagnostic developments in other pathogens.",2010 Aug 3,"['List, Claudia', 'Qi, Weihong', 'Maag, Eva', 'Gottstein, Bruno', 'Müller, Norbert', 'Felger, Ingrid']",PLoS Negl Trop Dis,,,True
743c5db7611d4af74204901e0ed3b6317a0bb3c4,PMC,"Knowledge, attitudes and practices towards pandemic influenza among cases, close contacts, and healthcare workers in tropical Singapore: a cross-sectional survey",http://dx.doi.org/10.1186/1471-2458-10-442,PMC2916908,20667076,CC BY,"BACKGROUND: Effective influenza pandemic management requires understanding of the factors influencing behavioral changes. We aim to determine the differences in knowledge, attitudes and practices in various different cohorts and explore the pertinent factors that influenced behavior in tropical Singapore. METHODS: We performed a cross-sectional knowledge, attitudes and practices survey in the Singapore military from mid-August to early-October 2009, among 3054 personnel in four exposure groups - laboratory-confirmed H1N1-2009 cases, close contacts of cases, healthcare workers, and general personnel. RESULTS: 1063 (34.8%) participants responded. The mean age was 21.4 (SE 0.2) years old. Close contacts had the highest knowledge score (71.7%, p = 0.004) while cases had the highest practice scores (58.8%, p < 0.001). There was a strong correlation between knowledge and practice scores (r = 0.27, p < 0.01) and knowledge and attitudes scores (r = 0.21, p < 0.01). The significant predictors of higher practice scores were higher knowledge scores (p < 0.001), Malay ethnicity (p < 0.001), exposure group (p < 0.05) and lower education level (p < 0.05). The significant predictors for higher attitudes scores were Malay ethnicity (p = 0.014) and higher knowledge scores (p < 0.001). The significant predictor for higher knowledge score was being a contact (p = 0.007). CONCLUSION: Knowledge is a significant influence on attitudes and practices in a pandemic, and personal experience influences practice behaviors. Efforts should be targeted at educating the general population to improve practices in the current pandemic, as well as for future epidemics.",2010 Jul 28,"['Yap, Jonathan', 'Lee, Vernon J', 'Yau, Teng Yan', 'Ng, Tze Pin', 'Tor, Phern-Chern']",BMC Public Health,,,True
545def8771357b4cb2875f5795a0760e97534cc9,PMC,Knowledge and attitudes of university students toward pandemic influenza: a cross-sectional study from Turkey,http://dx.doi.org/10.1186/1471-2458-10-413,PMC2918554,20626872,CC BY,"BACKGROUND: During an influenza pandemic, higher education institutions with large populations of young adults can become serious outbreak centers. Since outbreak management is essential to disease control, we aimed to examine university students' knowledge of and attitudes toward the pandemic influenza A/H1N1 and vaccination and other preventive measures. METHODS: A cross-sectional study was conducted among 402 first year university students at Yeditepe University in Istanbul, Turkey between 1(st )and 30(th )of November 2009. Data regarding socio-demographic characteristics of the students, perceptions, level of knowledge and attitudes toward influenza pandemic and prevention measures were collected by means of a self-administered questionnaire. The questionnaire was distributed by the students affiliated with SANITAS, a university club of students in health related sciences. RESULTS: 25.1% (101/402) of the study group perceived their personal risk of influenza as ""high"", while 40.5% (163/402) perceived it as ""moderate"", 20.6% (107/402) viewed it as ""low"" and 7.7% (31/402) indicated that it was ""unknown"". The risk perception of males was significantly lower than that of females (p = 0.004) and the risk perception among the students of health sciences was significantly lower than that of students of other sciences (p = 0.037). Within the study group, 72.1% (290/402) indicated that their main information source regarding H1N1 was the mass media. Health sciences students tended to rely more on the internet as an information source than other students (p = 0.015). The vast majority (92.8%; 373/402) of those interviewed indicated that they would not be vaccinated. The major concerns regarding vaccination had to do with the safety and side effects of the vaccine. Most of the participants (343/402, 85.3%) were carrying out one of prevention measures and the vast majority believed that hand washing, face mask and quarantina were effective measures for prevention. CONCLUSION: The participants had enough knowledge about H1N1 pandemic about the disease although there were still gaps and confusions in some areas. In the future, when planning management strategies regarding pandemics or outbreaks in higher education institutions, new strategies should be developed to promote positive health behaviour among university students compatible with the international guidelines. Main information source is mass media, so it seems that new policies must be developed to attract attention of students to use different and more scientific-based information sources.",2010 Jul 13,"['Akan, Hulya', 'Gurol, Yesim', 'Izbirak, Guldal', 'Ozdatlı, Sukran', 'Yilmaz, Gulden', 'Vitrinel, Ayca', 'Hayran, Osman']",BMC Public Health,,,True
af2d96a09d1d6fcfef38c823fac66da0dcbb299e,PMC,Influenza or not influenza: Analysis of a case of high fever that happened 2000 years ago in Biblical time,http://dx.doi.org/10.1186/1743-422X-7-169,PMC2918564,20663162,CC BY,"The Bible describes the case of a woman with high fever cured by our Lord Jesus Christ. Based on the information provided by the gospels of Mark, Matthew and Luke, the diagnosis and the possible etiology of the febrile illness is discussed. Infectious diseases continue to be a threat to humanity, and influenza has been with us since the dawn of human history. If the postulation is indeed correct, the woman with fever in the Bible is among one of the very early description of human influenza disease. Infectious diseases continue to be a threat to humanity, and influenza has been with us since the dawn of human history. We analysed a case of high fever that happened 2000 years ago in Biblical time and discussed possible etiologies.",2010 Jul 21,"['Hon, Kam LE', 'Ng, Pak C', 'Leung, Ting F']",Virol J,,,True
6fc8c1b4cfbd790cbe02c825fd6f9181b1fc6645,PMC,Reassuring and managing patients with concerns about swine flu: Qualitative interviews with callers to NHS Direct,http://dx.doi.org/10.1186/1471-2458-10-451,PMC2919480,20678192,CC BY,"BACKGROUND: During the early stages of the 2009 swine flu (influenza H1N1) outbreak, the large majority of patients who contacted the health services about the illness did not have it. In the UK, the NHS Direct telephone service was used by many of these patients. We used qualitative interviews to identify the main reasons why people approached NHS Direct with concerns about swine flu and to identify aspects of their contact which were reassuring, using a framework approach. METHODS: 33 patients participated in semi-structured interviews. All patients had telephoned NHS Direct between 11 and 14 May with concerns about swine flu and had been assessed as being unlikely to have the illness. RESULTS: Reasons for seeking advice about swine flu included: the presence of unexpectedly severe flu-like symptoms; uncertainties about how one can catch swine flu; concern about giving it to others; pressure from friends or employers; and seeking 'peace of mind.' Most participants found speaking to NHS Direct reassuring or useful. Helpful aspects included: having swine flu ruled out; receiving an alternative explanation for symptoms; clarification on how swine flu is transmitted; and the perceived credibility of NHS Direct. No-one reported anything that had increased their anxiety and only one participant subsequently sought additional advice about swine flu from elsewhere. CONCLUSIONS: Future major incidents involving other forms of chemical, biological or radiological hazards may also cause large numbers of unexposed people to seek health advice. Our data suggest that providing telephone triage and information is helpful in such instances, particularly where advice can be given via a trusted, pre-existing service.",2010 Aug 2,"['Rubin, G James', 'Amlôt, Richard', 'Carter, Holly', 'Large, Shirley', 'Wessely, Simon', 'Page, Lisa']",BMC Public Health,,,True
2b0d5260ad731335898da719538d30d414a9e39f,PMC,Mixed infections with Chlamydia and porcine epidemic diarrhea virus - a new in vitro model of chlamydial persistence,http://dx.doi.org/10.1186/1471-2180-10-201,PMC2919482,20663197,CC BY,"BACKGROUND: Chlamydiae induce persistent infections, which have been associated with a wide range of chronic diseases in humans and animals. Mixed infections with Chlamydia and porcine epidemic diarrhea virus (PEDV) may result in generation of persistent chlamydial infections. To test this hypothesis, an in vitro model of dual infection with cell culture-adapted PEDV and Chlamydia abortus or Chlamydia pecorum in Vero cells was established. RESULTS: Infected cultures were investigated by immunofluorescence (IF), transmission electron microscopy (TEM) and re-infection experiments. By IF, Chlamydia-infected cells showed normal inclusions after 39 hpi. Dual infections with Chlamydia abortus revealed a heterogenous mix of inclusion types including small inclusions consisting of aberrant bodies (ABs), medium-sized inclusions consisting of ABs and reticulate bodies and normal inclusions. Only aberrant inclusions were observable in dual infection experiments with Chlamydia pecorum and PEDV. TEM examinations of mixed infections with Chlamydia abortus and Chlamydia pecorum revealed aberrant chlamydial inclusions containing reticulate-like, pleomorphic ABs, which were up to 2 μm in diameter. No re-differentiation into elementary bodies (EBs) was detected. In re-infection experiments, co-infected cells produced fewer EBs than monoinfected cells. CONCLUSIONS: In the present study we confirm that PEDV co-infection alters the developmental cycle of member species of the family Chlamydiaceae, in a similar manner to other well-described persistence induction methods. Interestingly, this effect appears to be partially species-specific as Chlamydia pecorum appears more sensitive to PEDV co-infection than Chlamydia abortus, as evidenced by TEM and IF observations of a homogenous population of aberrant inclusions in PEDV - Chlamydia pecorum co-infections.",2010 Jul 27,"['Borel, Nicole', 'Dumrese, Claudia', 'Ziegler, Urs', 'Schifferli, Andrea', 'Kaiser, Carmen', 'Pospischil, Andreas']",BMC Microbiol,,,True
aa1f783a1af8b14cdbee5ea50cc0a78c56d7442e,PMC,Protective Efficacy of Cross-Reactive CD8(+) T Cells Recognising Mutant Viral Epitopes Depends on Peptide-MHC-I Structural Interactions and T Cell Activation Threshold,http://dx.doi.org/10.1371/journal.ppat.1001039,PMC2920842,20711359,CC BY,"Emergence of a new influenza strain leads to a rapid global spread of the virus due to minimal antibody immunity. Pre-existing CD8(+) T-cell immunity directed towards conserved internal viral regions can greatly ameliorate the disease. However, mutational escape within the T cell epitopes is a substantial issue for virus control and vaccine design. Although mutations can result in a loss of T cell recognition, some variants generate cross-reactive T cell responses. In this study, we used reverse genetics to modify the influenza NP(336–374) peptide at a partially-solvent exposed residue (N->A, NPN3A mutation) to assess the availability, effectiveness and mechanism underlying influenza-specific cross-reactive T cell responses. The engineered virus induced a diminished CD8(+) T cell response and selected a narrowed T cell receptor (TCR) repertoire within two Vβ regions (Vβ8.3 and Vβ9). This can be partially explained by the H-2D(b)NPN3A structure that showed a loss of several contacts between the NPN3A peptide and H-2D(b), including a contact with His155, a position known to play an important role in mediating TCR-pMHC-I interactions. Despite these differences, common cross-reactive TCRs were detected in both the naïve and immune NPN3A-specific TCR repertoires. However, while the NPN3A epitope primes memory T-cells that give an equivalent recall response to the mutant or wild-type (wt) virus, both are markedly lower than wt->wt challenge. Such decreased CD8(+) responses elicited after heterologous challenge resulted in delayed viral clearance from the infected lung. Furthermore, mice first exposed to the wt virus give a poor, low avidity response following secondary infection with the mutant. Thus, the protective efficacy of cross-reactive CD8(+) T cells recognising mutant viral epitopes depend on peptide-MHC-I structural interactions and functional avidity. Our study does not support vaccine strategies that include immunization against commonly selected cross-reactive variants with mutations at partially-solvent exposed residues that have characteristics comparable to NPN3A.",2010 Aug 12,"['Valkenburg, Sophie A.', 'Gras, Stephanie', 'Guillonneau, Carole', 'La Gruta, Nicole L.', 'Thomas, Paul G.', 'Purcell, Anthony W.', 'Rossjohn, Jamie', 'Doherty, Peter C.', 'Turner, Stephen J.', 'Kedzierska, Katherine']",PLoS Pathog,,,True
afc498abcb287239b8ea84ff535adf09158b0cfe,PMC,ANDES: Statistical tools for the ANalyses of DEep Sequencing,http://dx.doi.org/10.1186/1756-0500-3-199,PMC2921379,20633290,CC BY,"BACKGROUND: The advancements in DNA sequencing technologies have allowed researchers to progress from the analyses of a single organism towards the deep sequencing of a sample of organisms. With sufficient sequencing depth, it is now possible to detect subtle variations between members of the same species, or between mixed species with shared biomarkers, such as the 16S rRNA gene. However, traditional sequencing analyses of samples from largely homogeneous populations are often still based on multiple sequence alignments (MSA), where each sequence is placed along a separate row and similarities between aligned bases can be followed down each column. While this visual format is intuitive for a small set of aligned sequences, the representation quickly becomes cumbersome as sequencing depths cover loci hundreds or thousands of reads deep. FINDINGS: We have developed ANDES, a software library and a suite of applications, written in Perl and R, for the statistical ANalyses of DEep Sequencing. The fundamental data structure underlying ANDES is the position profile, which contains the nucleotide distributions for each genomic position resultant from a multiple sequence alignment (MSA). Tools include the root mean square deviation (RMSD) plot, which allows for the visual comparison of multiple samples on a position-by-position basis, and the computation of base conversion frequencies (transition/transversion rates), variation (Shannon entropy), inter-sample clustering and visualization (dendrogram and multidimensional scaling (MDS) plot), threshold-driven consensus sequence generation and polymorphism detection, and the estimation of empirically determined sequencing quality values. CONCLUSIONS: As new sequencing technologies evolve, deep sequencing will become increasingly cost-efficient and the inter and intra-sample comparisons of largely homogeneous sequences will become more common. We have provided a software package and demonstrated its application on various empirically-derived datasets. Investigators may download the software from Sourceforge at https://sourceforge.net/projects/andestools.",2010 Jul 15,"['Li, Kelvin', 'Venter, Eli', 'Yooseph, Shibu', 'Stockwell, Timothy B', 'Eckerle, Lance D', 'Denison, Mark R', 'Spiro, David J', 'Methé, Barbara A']",BMC Res Notes,,,True
40a30eb6f76c29d52d4ee9c7619f9f8bbfef796a,PMC,Perceptions and behaviors related to hand hygiene for the prevention of H1N1 influenza transmission among Korean university students during the peak pandemic period,http://dx.doi.org/10.1186/1471-2334-10-222,PMC2922213,20663229,CC BY,"BACKGROUND: This study was performed to better assess the perceptions, motivating factors, and behaviors associated with the use of hand washing to prevent H1N1 influenza transmission during the peak pandemic period in Korea. METHODS: A cross-sectional survey questionnaire was completed by 942 students at a university campus in Suwon, Korea, between December 1 and 8, 2009. The survey included questions regarding individual perceptions, motivating factors, and behaviors associated with hand washing for the prevention of H1N1 influenza transmission. RESULTS: Compared to one year prior, 30.3% of participants reported increasing their hand washing frequency. Female students were more likely to practice more frequent hand washing. Women also perceived the effectiveness of hand washing to be lower, and illness severity and personal susceptibility to H1N1 infection to be higher. Study participants who were female (OR: 1.79-3.90) who perceived of hand washing to be effective (OR: 1.34-12.15) and illness severity to be greater (OR: 1.00-3.12) washed their hands more frequently. CONCLUSIONS: Korean students increased their frequency of hand hygiene practices during the pandemic, with significant gender differences existing in the attitudes and behaviors related to the use of hand hygiene as a means of disease prevention. Here, the factors that affected hand washing behavior were similar to those identified at the beginning of the H1N1 or SARS pandemics, suggesting that public education campaigns regarding hand hygiene are effective in altering individual hand hygiene habits during the peak periods of influenza transmission.",2010 Jul 28,"['Park, Jae-Hyun', 'Cheong, Hae-Kwan', 'Son, Dae-Yong', 'Kim, Seon-Ung', 'Ha, Chang-Min']",BMC Infect Dis,,,True
1552cf77b6385950e197c67c2ed55ed6e1879ced,PMC,"Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold",http://dx.doi.org/10.1186/1465-9921-11-108,PMC2923116,20696083,CC BY,"BACKGROUND: The common cold, the most prevalent contagious viral disease in humans still lacks a safe and effective antiviral treatment. Iota-Carrageenan is broadly active against respiratory viruses in-vitro and has an excellent safety profile. This study investigated the efficacy and safety of an Iota-Carrageenan nasal spray in patients with common cold symptoms. METHODS: In a randomized, double-blind, placebo-controlled exploratory trial, 35 human subjects suffering from early symptoms of common cold received Iota-Carrageenan (0.12%) in a saline solution three times daily for 4 days, compared to placebo. RESULTS: Administration of Iota-Carrageenan nasal spray reduced the symptoms of common cold (p = 0.046) and the viral load in nasal lavages (p = 0.009) in patients with early symptoms of common cold. Pro-inflammatory mediators FGF-2, Fractalkine, GRO, G-CSF, IL-8, IL-1α, IP-10, IL-10, and IFN-α2 were reduced in the Iota-Carrageenan group. CONCLUSIONS: Iota-Carrageenan nasal spray appears to be a promising treatment for safe and effective treatment of early symptoms of common cold. Larger trials are indicated to confirm the results.",2010 Aug 10,"['Eccles, Ron', 'Meier, Christiane', 'Jawad, Martez', 'Weinmüllner, Regina', 'Grassauer, Andreas', 'Prieschl-Grassauer, Eva']",Respir Res,,,True
95c1dc78f1775a83d61ad2517a26844f9a3c46b9,PMC,Enterovirus type 71 2A protease functions as a transcriptional activator in yeast,http://dx.doi.org/10.1186/1423-0127-17-65,PMC2923119,20682079,CC BY,"Enterovirus type 71 (EV71) 2A protease exhibited strong transcriptional activity in yeast cells. The transcriptional activity of 2A protease was independent of its protease activity. EV71 2A protease retained its transcriptional activity after truncation of 40 amino acids at the N-terminus but lost this activity after truncation of 60 amino acids at the N-terminus or deletion of 20 amino acids at the C-terminus. Thus, the acidic domain at the C-terminus of this protein is essential for its transcriptional activity. Indeed, deletion of amino acids from 146 to 149 (EAME) in this acidic domain lost the transcriptional activity of EV71 2A protein though still retained its protease activity. EV71 2A protease was detected both in the cytoplasm and nucleus using confocal microscopy analysis. Coxsackie virus B3 2A protease also exhibited transcriptional activity in yeast cells. As expected, an acidic domain in the C-terminus of Coxsackie virus B3 2A protease was also identified. Truncation of this acidic domain resulted in the loss of transcriptional activity. Interestingly, this acidic region of poliovirus 2A protease is critical for viral RNA replication. The transcriptional activity of the EV71 or Coxsackie virus B3 2A protease should play a role in viral replication and/or pathogenesis.",2010 Aug 4,"['Yang, Chee-Hing', 'Li, Hui-Chun', 'Jiang, Jeng-Geng', 'Hsu, Che-Fang', 'Wang, Yi-Jen', 'Lai, Meng-Jiun', 'Juang, Yue-Li', 'Lo, Shih-Yen']",J Biomed Sci,,,True
ab371ed38caa53c720fd4c0333e1bf4de84550f1,PMC,Cancer Biomarker Discovery: The Entropic Hallmark,http://dx.doi.org/10.1371/journal.pone.0012262,PMC2923618,20805891,CC BY,"BACKGROUND: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. METHODOLOGY/PRINCIPAL FINDINGS: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. CONCLUSIONS/SIGNIFICANCE: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-througput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases.",2010 Aug 18,"['Berretta, Regina', 'Moscato, Pablo']",PLoS One,,,True
a0016598cd0ea40803d8ab461f4ebdba9abe94c1,PMC,Adaptive Contact Networks Change Effective Disease Infectiousness and Dynamics,http://dx.doi.org/10.1371/journal.pcbi.1000895,PMC2924249,20808884,CC BY,"Human societies are organized in complex webs that are constantly reshaped by a social dynamic which is influenced by the information individuals have about others. Similarly, epidemic spreading may be affected by local information that makes individuals aware of the health status of their social contacts, allowing them to avoid contact with those infected and to remain in touch with the healthy. Here we study disease dynamics in finite populations in which infection occurs along the links of a dynamical contact network whose reshaping may be biased based on each individual's health status. We adopt some of the most widely used epidemiological models, investigating the impact of the reshaping of the contact network on the disease dynamics. We derive analytical results in the limit where network reshaping occurs much faster than disease spreading and demonstrate numerically that this limit extends to a much wider range of time scales than one might anticipate. Specifically, we show that from a population-level description, disease propagation in a quickly adapting network can be formulated equivalently as disease spreading on a well-mixed population but with a rescaled infectiousness. We find that for all models studied here – SI, SIS and SIR – the effective infectiousness of a disease depends on the population size, the number of infected in the population, and the capacity of healthy individuals to sever contacts with the infected. Importantly, we indicate how the use of available information hinders disease progression, either by reducing the average time required to eradicate a disease (in case recovery is possible), or by increasing the average time needed for a disease to spread to the entire population (in case recovery or immunity is impossible).",2010 Aug 19,"['Van Segbroeck, Sven', 'Santos, Francisco C.', 'Pacheco, Jorge M.']",PLoS Comput Biol,,,True
d61d66e22524793eb025db202a84eaaae50da2bf,PMC,Adaptive Contact Networks Change Effective Disease Infectiousness and Dynamics,http://dx.doi.org/10.1371/journal.pcbi.1000895,PMC2924249,20808884,CC BY,"Human societies are organized in complex webs that are constantly reshaped by a social dynamic which is influenced by the information individuals have about others. Similarly, epidemic spreading may be affected by local information that makes individuals aware of the health status of their social contacts, allowing them to avoid contact with those infected and to remain in touch with the healthy. Here we study disease dynamics in finite populations in which infection occurs along the links of a dynamical contact network whose reshaping may be biased based on each individual's health status. We adopt some of the most widely used epidemiological models, investigating the impact of the reshaping of the contact network on the disease dynamics. We derive analytical results in the limit where network reshaping occurs much faster than disease spreading and demonstrate numerically that this limit extends to a much wider range of time scales than one might anticipate. Specifically, we show that from a population-level description, disease propagation in a quickly adapting network can be formulated equivalently as disease spreading on a well-mixed population but with a rescaled infectiousness. We find that for all models studied here – SI, SIS and SIR – the effective infectiousness of a disease depends on the population size, the number of infected in the population, and the capacity of healthy individuals to sever contacts with the infected. Importantly, we indicate how the use of available information hinders disease progression, either by reducing the average time required to eradicate a disease (in case recovery is possible), or by increasing the average time needed for a disease to spread to the entire population (in case recovery or immunity is impossible).",2010 Aug 19,"['Van Segbroeck, Sven', 'Santos, Francisco C.', 'Pacheco, Jorge M.']",PLoS Comput Biol,,,True
217e7ecb495478a12b89de6ab9d03e629f478752,PMC,Up-regulation of p21 and TNF-α is mediated in lycorine-induced death of HL-60 cells,http://dx.doi.org/10.1186/1475-2867-10-25,PMC2924328,20682078,CC BY,"BACKGROUND: Leukemia is one of the most life-threatening cancers today, and acute promyelogenous leukemia (APL) is a common type of leukemia. Many natural compounds have already been found to exhibit significant anti-tumor effects. Lycorine, a natural alkaloid extracted from Amaryllidaceae, exhibited anti-leukemia effects in vitro and in vivo. The survival rate of HL-60 cells exposed to lycorine was decreased, cell growth was slowed down, and cell regeneration potential was inhibited. HL-60 cells exhibited typical apoptotic characteristic. Lycorine can suppress leukemia growth and reduce cell survival and inducing apoptosis of tumor cells. The purpose of this work is to elucidate the mechanism by which lycorine induces APL cells. RESULTS: When HL-60 cells were treated with different concentration of lycorine, the expression of p21 and TNF-α was up-regulated in a concentration-dependent manner as shown by real-time quantitative reverse transcriptase-polymerase chain reaction and Western blotting. Lycorine also down-regulated p21-related gene expression, including Cdc2, Cyclin B, Cdk2 and Cyclin E, promoted Bid truncation, decreased IκB phosphorylation and blocked NF-κB nuclear import. Cytochrome c was released from mitochondria as observed with confocal laser microscopy. CONCLUSIONS: The TNF-α signal transduction pathway and p21-mediated cell-cycle inhibition were involved in the apoptosis of HL-60 cells induced by lycorine. These results contribute to the development of new lycorine-based anti-leukemia drugs.",2010 Aug 4,"['Liu, Jing', 'Hu, Ji-liang', 'Shi, Bi-Wei', 'He, Yan', 'Hu, Wei-Xin']",Cancer Cell Int,,,True
ffaa82089f00d6e0b4710f59b4016c59c5879ea7,PMC,Diagnostic Methods for Feline Coronavirus: A Review,http://dx.doi.org/10.4061/2010/809480,PMC2926681,20798771,CC BY,"Feline coronaviruses (FCoVs) are found throughout the world. Infection with FCoV can result in a diverse range of signs from clinically inapparent infections to a highly fatal disease called feline infectious peritonitis (FIP). FIP is one of the most serious viral diseases of cats. While there is neither an effective vaccine, nor a curative treatment for FIP, a diagnostic protocol for FCoV would greatly assist in the management and control of the virus. Clinical findings in FIP are non-specific and not helpful in making a differential diagnosis. Haematological and biochemical abnormalities in FIP cases are also non-specific. The currently available serological tests have low specificity and sensitivity for detection of active infection and cross-react with FCoV strains of low pathogenicity, the feline enteric coronaviruses (FECV). Reverse transcriptase polymerase chain reaction (RT-PCR) has been used to detect FCoV and is rapid and sensitive, but results must be interpreted in the context of clinical findings. At present, a definitive diagnosis of FIP can be established only by histopathological examination of biopsies. This paper describes and compares diagnostic methods for FCoVs and includes a brief account of the virus biology, epidemiology, and pathogenesis.",2010 Jul 28,"['Sharif, Saeed', 'Arshad, Siti Suri', 'Hair-Bejo, Mohd', 'Omar, Abdul Rahman', 'Zeenathul, Nazariah Allaudin', 'Alazawy, Amer']",Vet Med Int,,,True
7875c1a9783593b90bb90b99f285583067a3f433,PMC,Establishment of Fruit Bat Cells (Rousettus aegyptiacus) as a Model System for the Investigation of Filoviral Infection,http://dx.doi.org/10.1371/journal.pntd.0000802,PMC2927428,20808767,CC BY,"BACKGROUND: The fruit bat species Rousettus aegyptiacus was identified as a potential reservoir for the highly pathogenic filovirus Marburg virus. To establish a basis for a molecular understanding of the biology of filoviruses in the reservoir host, we have adapted a set of molecular tools for investigation of filovirus replication in a recently developed cell line, R06E, derived from the species Rousettus aegyptiacus. METHODOLOGY/PRINCIPAL FINDINGS: Upon infection with Ebola or Marburg viruses, R06E cells produced viral titers comparable to VeroE6 cells, as shown by TCID(50) analysis. Electron microscopic analysis of infected cells revealed morphological signs of filovirus infection as described for human- and monkey-derived cell lines. Using R06E cells, we detected an unusually high amount of intracellular viral proteins, which correlated with the accumulation of high numbers of filoviral nucleocapsids in the cytoplasm. We established protocols to produce Marburg infectious virus-like particles from R06E cells, which were then used to infect naïve target cells to investigate primary transcription. This was not possible with other cell lines previously tested. Moreover, we established protocols to reliably rescue recombinant Marburg viruses from R06E cells. CONCLUSION/SIGNIFICANCE: These data indicated that R06E cells are highly suitable to investigate the biology of filoviruses in cells derived from their presumed reservoir.",2010 Aug 24,"['Krähling, Verena', 'Dolnik, Olga', 'Kolesnikova, Larissa', 'Schmidt-Chanasit, Jonas', 'Jordan, Ingo', 'Sandig, Volker', 'Günther, Stephan', 'Becker, Stephan']",PLoS Negl Trop Dis,,,True
eb6bcd87e93e2bac6bd7b03367102b0a05e458e3,PMC,Ferret badger rabies origin and its revisited importance as potential source of rabies transmission in Southeast China,http://dx.doi.org/10.1186/1471-2334-10-234,PMC2927599,20691095,CC BY,"BACKGROUND: The frequent occurrence of ferret badger-associated human rabies cases in southeast China highlights the lack of laboratory-based surveillance and urges revisiting the potential importance of this animal in rabies transmission. To determine if the ferret badgers actually contribute to human and dog rabies cases, and the possible origin of the ferret badger-associated rabies in the region, an active rabies survey was conducted to determine the frequency of rabies infection and seroprevalence in dogs and ferret badgers. METHODS: A retrospective survey on rabies epidemics was performed in Zhejiang, Jiangxi and Anhui provinces in southeast China. The brain tissues from ferret badgers and dogs were assayed by fluorescent antibody test. Rabies virus was isolated and sequenced for phylogenetic analysis. The sera from ferret badgers and dogs were titrated using rabies virus neutralizing antibodies (VNA) test. RESULTS: The ferret badgers presented a higher percentage of rabies seroconversion than dogs did in the endemic region, reaching a maximum of 95% in the collected samples. Nine ferret badger-associated rabies viruses were isolated, sequenced, and were phylogenetically clustered as a separate group. Nucleotide sequence revealed 99.4-99.8% homology within the ferret badger isolates, and 83-89% homology to the dog isolates in the nucleoprotein and glycoprotein genes in the same rabies endemic regions. CONCLUSIONS: Our data suggest ferret badger-associated rabies has likely formed as an independent enzootic originating from dogs during the long-term rabies infestation in southeast China. The eventual role of FB rabies in public health remains unclear. However, management of ferret badger bites, rabies awareness and control in the related regions should be an immediate need.",2010 Aug 6,"['Liu, Ye', 'Zhang, Shoufeng', 'Wu, Xianfu', 'Zhao, Jinghui', 'Hou, Yanli', 'Zhang, Fei', 'Velasco-Villa, Andres', 'Rupprecht, Charles E', 'Hu, Rongliang']",BMC Infect Dis,,,True
8a1127271041cb420bec9aa4be4afa5d62b2b3b7,PMC,Proteomics Comparison of Cerebrospinal Fluid of Relapsing Remitting and Primary Progressive Multiple Sclerosis,http://dx.doi.org/10.1371/journal.pone.0012442,PMC2929207,20805994,CC BY,"BACKGROUND: Based on clinical representation of disease symptoms multiple sclerosis (MScl) patients can be divided into two major subtypes; relapsing remitting (RR) MScl (85–90%) and primary progressive (PP) MScl (10–15%). Proteomics analysis of cerebrospinal fluid (CSF) has detected a number of proteins that were elevated in MScl patients. Here we specifically aimed to differentiate between the PP and RR subtypes of MScl by comparing CSF proteins. METHODOLOGY/PRINCIPAL FINDINGS: CSF samples (n = 31) were handled according to the same protocol for quantitative mass spectrometry measurements we reported previously. In the comparison of PP MScl versus RR MScl we observed a number of differentially abundant proteins, such as protein jagged-1 and vitamin D-binding protein. Protein jagged-1 was over three times less abundant in PP MScl compared to RR MScl. Vitamin D-binding protein was only detected in the RR MScl samples. These two proteins were validated by independent techniques (western blot and ELISA) as differentially abundant in the comparison between both MScl types. CONCLUSIONS/SIGNIFICANCE: The main finding of this comparative study is the observation that the proteome profiles of CSF in PP and RR MScl patients overlap to a large extent. Still, a number of differences could be observed. Protein jagged-1 is a ligand for multiple Notch receptors and involved in the mediation of Notch signaling. It is suggested in literature that the Notch pathway is involved in the remyelination of MScl lesions. Aberration of normal homeostasis of Vitamin D, of which approximately 90% is bound to vitamin D-binding protein, has been widely implicated in MScl for some years now. Vitamin D directly and indirectly regulates the differentiation, activation of CD4+ T-lymphocytes and can prevent the development of autoimmune processes, and so it may be involved in neuroprotective elements in MScl.",2010 Aug 27,"['Stoop, Marcel P.', 'Singh, Vaibhav', 'Dekker, Lennard J.', 'Titulaer, Mark K.', 'Stingl, Christoph', 'Burgers, Peter C.', 'Sillevis Smitt, Peter A. E.', 'Hintzen, Rogier Q.', 'Luider, Theo M.']",PLoS One,,,True
797c6ecb7d0eb5d6eb5ea5f081a3c4cc78be5bd2,PMC,Including the public in pandemic planning: a deliberative approach,http://dx.doi.org/10.1186/1471-2458-10-501,PMC2931476,20718996,CC BY,"BACKGROUND: Against a background of pandemic threat posed by SARS and avian H5N1 influenza, this study used deliberative forums to elucidate informed community perspectives on aspects of pandemic planning. METHODS: Two deliberative forums were carried out with members of the South Australian community. The forums were supported by a qualitative study with adults and youths, systematic reviews of the literature and the involvement of an extended group of academic experts and policy makers. The forum discussions were recorded with simultaneous transcription and analysed thematically. RESULTS: Participants allocated scarce resources of antiviral drugs and pandemic vaccine based on a desire to preserve society function in a time of crisis. Participants were divided on the acceptability of social distancing and quarantine measures. However, should such measures be adopted, they thought that reasonable financial, household and psychological support was essential. In addition, provided such support was present, the participants, in general, were willing to impose strict sanctions on those who violated quarantine and social distancing measures. CONCLUSIONS: The recommendations from the forums suggest that the implementation of pandemic plans in a severe pandemic will be challenging, but not impossible. Implementation may be more successful if the public is engaged in pandemic planning before a pandemic, effective communication of key points is practiced before and during a pandemic and if judicious use is made of supportive measures to assist those in quarantine or affected by social isolation measures.",2010 Aug 19,"['Braunack-Mayer, Annette J', 'Street, Jackie M', 'Rogers, Wendy A', 'Givney, Rodney', 'Moss, John R', 'Hiller, Janet E']",BMC Public Health,,,True
6598644894c24fccef62e4df45e859f023bea4c6,PMC,Risk factors for the evolutionary emergence of pathogens,http://dx.doi.org/10.1098/rsif.2010.0123,PMC2935601,20410190,CC BY,"Recent outbreaks of novel infectious diseases (e.g. SARS, influenza H1N1) have highlighted the threat of cross-species pathogen transmission. When first introduced to a population, a pathogen is often poorly adapted to its new host and must evolve in order to escape extinction. Theoretical arguments and empirical studies have suggested various factors to explain why some pathogens emerge and others do not, including host contact structure, pathogen adaptive pathways and mutation rates. Using a multi-type branching process, we model the spread of an introduced pathogen evolving through several strains. Extending previous models, we use a network-based approach to separate host contact patterns from pathogen transmissibility. We also allow for arbitrary adaptive pathways. These generalizations lead to novel predictions regarding the impact of hypothesized risk factors. Pathogen fitness depends on the host population in which it circulates, and the ‘riskiest’ contact distribution and adaptive pathway depend on initial transmissibility. Emergence probability is sensitive to mutation probabilities and number of adaptive steps required, with the possibility of large adaptive steps (e.g. simultaneous point mutations or recombination) having a dramatic effect. In most situations, increasing overall mutation probability increases the risk of emergence; however, notable exceptions arise when deleterious mutations are available.",2010 Oct 6,"['Alexander, H. K.', 'Day, T.']",J R Soc Interface,,,True
b1d31bf64148c3dabdd5b8a288b78c0c6d3a7cea,PMC,Curating the innate immunity interactome,http://dx.doi.org/10.1186/1752-0509-4-117,PMC2936296,20727158,CC BY,"BACKGROUND: The innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks. Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks. A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks. InnateDB (http://www.innatedb.com) is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity. RESULTS: Here, we describe the InnateDB curation project, which is manually annotating the human and mouse innate immunity interactome in rich contextual detail, and present our novel curation software system, which has been developed to ensure interactions are curated in a highly accurate and data-standards compliant manner. To date, over 13,000 interactions (protein, DNA and RNA) have been curated from the biomedical literature. Here, we present data, illustrating how InnateDB curation of the innate immunity interactome has greatly enhanced network and pathway annotation available for systems-level analysis and discuss the challenges that face such curation efforts. Significantly, we provide several lines of evidence that analysis of the innate immunity interactome has the potential to identify novel signalling, transcriptional and post-transcriptional regulators of innate immunity. Additionally, these analyses also provide insight into the cross-talk between innate immunity pathways and other biological processes, such as adaptive immunity, cancer and diabetes, and intriguingly, suggests links to other pathways, which as yet, have not been implicated in the innate immune response. CONCLUSIONS: In summary, curation of the InnateDB interactome provides a wealth of information to enable systems-level analysis of innate immunity.",2010 Aug 20,"['Lynn, David J', 'Chan, Calvin', 'Naseer, Misbah', 'Yau, Melissa', 'Lo, Raymond', 'Sribnaia, Anastasia', 'Ring, Giselle', 'Que, Jaimmie', 'Wee, Kathleen', 'Winsor, Geoffrey L', 'Laird, Matthew R', 'Breuer, Karin', 'Foroushani, Amir K', 'Brinkman, Fiona SL', 'Hancock, Robert EW']",BMC Syst Biol,,,True
1b5d310d0656503b1d2fbc612625496a3266ae16,PMC,Serological characterization of guinea pigs infected with H3N2 human influenza or immunized with hemagglutinin protein,http://dx.doi.org/10.1186/1743-422X-7-200,PMC2939558,20735849,CC BY,"BACKGROUND: Recent and previous studies have shown that guinea pigs can be infected with, and transmit, human influenza viruses. Therefore guinea pig may be a useful animal model for better understanding influenza infection and assessing vaccine strategies. To more fully characterize the model, antibody responses following either infection/re-infection with human influenza A/Wyoming/03/2003 H3N2 or immunization with its homologous recombinant hemagglutinin (HA) protein were studied. RESULTS: Serological samples were collected and tested for anti-HA immunoglobulin by ELISA, antiviral antibodies by hemagglutination inhibition (HI), and recognition of linear epitopes by peptide scanning (PepScan). Animals inoculated with infectious virus demonstrated pronounced viral replication and subsequent serological conversion. Animals either immunized with the homologous HA antigen or infected, showed a relatively rapid rise in antibody titers to the HA glycoprotein in ELISA assays. Antiviral antibodies, measured by HI assay, were detectable after the second inoculation. PepScan data identified both previously recognized and newly defined linear epitopes. CONCLUSIONS: Infection and/or recombinant HA immunization of guinea pigs with H3N2 Wyoming influenza virus resulted in a relatively rapid production of viral-specific antibody thus demonstrating the strong immunogenicity of the major viral structural proteins in this animal model for influenza infection. The sensitivity of the immune response supports the utility of the guinea pig as a useful animal model of influenza infection and immunization.",2010 Aug 24,"['Bushnell, Ruth V', 'Tobin, John K', 'Long, Jinxue', 'Schultz-Cherry, Stacey', 'Chaudhuri, A Ray', 'Nara, Peter L', 'Tobin, Gregory J']",Virol J,,,True
24d774f5b08d9ca987d0d23927d92ba23f131931,PMC,Detection of swine transmissible gastroenteritis coronavirus using loop-mediated isothermal amplification,http://dx.doi.org/10.1186/1743-422X-7-206,PMC2939561,20799985,CC BY,"A conserved nucleic acid fragment of the nucleocapsid gene of Swine Transmissible Gastroenteritis Coronavirus (TGEV) was chosen as the target, six special primers were designed successfully. Loop-mediated isothermal amplification (LAMP) was developed to detect the TGEV by incubation at 60°C for 1 h and the product specificity was confirmed by HphI digestion. Standard curves with high accuracy for TGEV quantization was constructed by adding 1 × SYBR greenI in the LAMP reaction. The assay established in this study was found to detect only the TGEV and no cross-reaction with other viruses, demonstrating its high specificity. By using serial sample dilutions as templates, the detection limit of LAMP was about 10 pg RNA, 10 times more sensitive than that of PCR and could be comparable to the nest-PCR.",2010 Aug 29,"['Chen, Qin', 'Li, Jian', 'Fang, Xue-En', 'Xiong, Wei']",Virol J,,,True
22f1e46f69ea11771ee26f499b234bd3ff1bb88b,PMC,Predictive Power of Air Travel and Socio-Economic Data for Early Pandemic Spread,http://dx.doi.org/10.1371/journal.pone.0012763,PMC2939898,20856678,CC BY,"BACKGROUND: Controlling the pandemic spread of newly emerging diseases requires rapid, targeted allocation of limited resources among nations. Critical, early control steps would be greatly enhanced if the key risk factors can be identified that accurately predict early disease spread immediately after emergence. METHODOLOGY/PRINCIPAL FINDINGS: Here, we examine the role of travel, trade, and national healthcare resources in predicting the emergence and initial spread of 2009 A/H1N1 influenza. We find that incorporating national healthcare resource data into our analyses allowed a much greater capacity to predict the international spread of this virus. In countries with lower healthcare resources, the reporting of 2009 A/H1N1 cases was significantly delayed, likely reflecting a lower capacity for testing and reporting, as well as other socio-political issues. We also report substantial international trade in live swine and poultry in the decade preceding the pandemic which may have contributed to the emergence and mixed genotype of this pandemic strain. However, the lack of knowledge of recent evolution of each H1N1 viral gene segment precludes the use of this approach to determine viral origins. CONCLUSIONS/SIGNIFICANCE: We conclude that strategies to prevent pandemic influenza virus emergence and spread in the future should include: 1) enhanced surveillance for strains resulting from reassortment in traded livestock; 2) rapid deployment of control measures in the initial spreading phase to countries where travel data predict the pathogen will reach and to countries where lower healthcare resources will likely cause delays in reporting. Our results highlight the benefits, for all parties, when higher income countries provide additional healthcare resources for lower income countries, particularly those that have high air traffic volumes. In particular, international authorities should prioritize aid to those poorest countries where both the risk of emerging infectious diseases and air traffic volume is highest. This strategy will result in earlier detection of pathogens and a reduction in the impact of future pandemics.",2010 Sep 15,"['Hosseini, Parviez', 'Sokolow, Susanne H.', 'Vandegrift, Kurt J.', 'Kilpatrick, A. Marm', 'Daszak, Peter']",PLoS One,,,True
9d2d0abefdd08e5ab7311a1f9dd2c8ad9d34d4dd,PMC,Predictive Power of Air Travel and Socio-Economic Data for Early Pandemic Spread,http://dx.doi.org/10.1371/journal.pone.0012763,PMC2939898,20856678,CC BY,"BACKGROUND: Controlling the pandemic spread of newly emerging diseases requires rapid, targeted allocation of limited resources among nations. Critical, early control steps would be greatly enhanced if the key risk factors can be identified that accurately predict early disease spread immediately after emergence. METHODOLOGY/PRINCIPAL FINDINGS: Here, we examine the role of travel, trade, and national healthcare resources in predicting the emergence and initial spread of 2009 A/H1N1 influenza. We find that incorporating national healthcare resource data into our analyses allowed a much greater capacity to predict the international spread of this virus. In countries with lower healthcare resources, the reporting of 2009 A/H1N1 cases was significantly delayed, likely reflecting a lower capacity for testing and reporting, as well as other socio-political issues. We also report substantial international trade in live swine and poultry in the decade preceding the pandemic which may have contributed to the emergence and mixed genotype of this pandemic strain. However, the lack of knowledge of recent evolution of each H1N1 viral gene segment precludes the use of this approach to determine viral origins. CONCLUSIONS/SIGNIFICANCE: We conclude that strategies to prevent pandemic influenza virus emergence and spread in the future should include: 1) enhanced surveillance for strains resulting from reassortment in traded livestock; 2) rapid deployment of control measures in the initial spreading phase to countries where travel data predict the pathogen will reach and to countries where lower healthcare resources will likely cause delays in reporting. Our results highlight the benefits, for all parties, when higher income countries provide additional healthcare resources for lower income countries, particularly those that have high air traffic volumes. In particular, international authorities should prioritize aid to those poorest countries where both the risk of emerging infectious diseases and air traffic volume is highest. This strategy will result in earlier detection of pathogens and a reduction in the impact of future pandemics.",2010 Sep 15,"['Hosseini, Parviez', 'Sokolow, Susanne H.', 'Vandegrift, Kurt J.', 'Kilpatrick, A. Marm', 'Daszak, Peter']",PLoS One,,,False
8228f444067a2fb0122111798ff462a4a92b59a6,PMC,Predictive Power of Air Travel and Socio-Economic Data for Early Pandemic Spread,http://dx.doi.org/10.1371/journal.pone.0012763,PMC2939898,20856678,CC BY,"BACKGROUND: Controlling the pandemic spread of newly emerging diseases requires rapid, targeted allocation of limited resources among nations. Critical, early control steps would be greatly enhanced if the key risk factors can be identified that accurately predict early disease spread immediately after emergence. METHODOLOGY/PRINCIPAL FINDINGS: Here, we examine the role of travel, trade, and national healthcare resources in predicting the emergence and initial spread of 2009 A/H1N1 influenza. We find that incorporating national healthcare resource data into our analyses allowed a much greater capacity to predict the international spread of this virus. In countries with lower healthcare resources, the reporting of 2009 A/H1N1 cases was significantly delayed, likely reflecting a lower capacity for testing and reporting, as well as other socio-political issues. We also report substantial international trade in live swine and poultry in the decade preceding the pandemic which may have contributed to the emergence and mixed genotype of this pandemic strain. However, the lack of knowledge of recent evolution of each H1N1 viral gene segment precludes the use of this approach to determine viral origins. CONCLUSIONS/SIGNIFICANCE: We conclude that strategies to prevent pandemic influenza virus emergence and spread in the future should include: 1) enhanced surveillance for strains resulting from reassortment in traded livestock; 2) rapid deployment of control measures in the initial spreading phase to countries where travel data predict the pathogen will reach and to countries where lower healthcare resources will likely cause delays in reporting. Our results highlight the benefits, for all parties, when higher income countries provide additional healthcare resources for lower income countries, particularly those that have high air traffic volumes. In particular, international authorities should prioritize aid to those poorest countries where both the risk of emerging infectious diseases and air traffic volume is highest. This strategy will result in earlier detection of pathogens and a reduction in the impact of future pandemics.",2010 Sep 15,"['Hosseini, Parviez', 'Sokolow, Susanne H.', 'Vandegrift, Kurt J.', 'Kilpatrick, A. Marm', 'Daszak, Peter']",PLoS One,,,False
d7a0bbfc13566c612f060bab06c96edf195be539,PMC,Predictive Power of Air Travel and Socio-Economic Data for Early Pandemic Spread,http://dx.doi.org/10.1371/journal.pone.0012763,PMC2939898,20856678,CC BY,"BACKGROUND: Controlling the pandemic spread of newly emerging diseases requires rapid, targeted allocation of limited resources among nations. Critical, early control steps would be greatly enhanced if the key risk factors can be identified that accurately predict early disease spread immediately after emergence. METHODOLOGY/PRINCIPAL FINDINGS: Here, we examine the role of travel, trade, and national healthcare resources in predicting the emergence and initial spread of 2009 A/H1N1 influenza. We find that incorporating national healthcare resource data into our analyses allowed a much greater capacity to predict the international spread of this virus. In countries with lower healthcare resources, the reporting of 2009 A/H1N1 cases was significantly delayed, likely reflecting a lower capacity for testing and reporting, as well as other socio-political issues. We also report substantial international trade in live swine and poultry in the decade preceding the pandemic which may have contributed to the emergence and mixed genotype of this pandemic strain. However, the lack of knowledge of recent evolution of each H1N1 viral gene segment precludes the use of this approach to determine viral origins. CONCLUSIONS/SIGNIFICANCE: We conclude that strategies to prevent pandemic influenza virus emergence and spread in the future should include: 1) enhanced surveillance for strains resulting from reassortment in traded livestock; 2) rapid deployment of control measures in the initial spreading phase to countries where travel data predict the pathogen will reach and to countries where lower healthcare resources will likely cause delays in reporting. Our results highlight the benefits, for all parties, when higher income countries provide additional healthcare resources for lower income countries, particularly those that have high air traffic volumes. In particular, international authorities should prioritize aid to those poorest countries where both the risk of emerging infectious diseases and air traffic volume is highest. This strategy will result in earlier detection of pathogens and a reduction in the impact of future pandemics.",2010 Sep 15,"['Hosseini, Parviez', 'Sokolow, Susanne H.', 'Vandegrift, Kurt J.', 'Kilpatrick, A. Marm', 'Daszak, Peter']",PLoS One,,,False
c73aa8452ccd63758df52737aae67450f078e76b,PMC,The N-Terminal Domain of the Arenavirus L Protein Is an RNA Endonuclease Essential in mRNA Transcription,http://dx.doi.org/10.1371/journal.ppat.1001038,PMC2940758,20862324,CC BY,"Arenaviridae synthesize viral mRNAs using short capped primers presumably acquired from cellular transcripts by a ‘cap-snatching’ mechanism. Here, we report the crystal structure and functional characterization of the N-terminal 196 residues (NL1) of the L protein from the prototypic arenavirus: lymphocytic choriomeningitis virus. The NL1 domain is able to bind and cleave RNA. The 2.13 Å resolution crystal structure of NL1 reveals a type II endonuclease α/β architecture similar to the N-terminal end of the influenza virus PA protein. Superimposition of both structures, mutagenesis and reverse genetics studies reveal a unique spatial arrangement of key active site residues related to the PD…(D/E)XK type II endonuclease signature sequence. We show that this endonuclease domain is conserved and active across the virus families Arenaviridae, Bunyaviridae and Orthomyxoviridae and propose that the arenavirus NL1 domain is the Arenaviridae cap-snatching endonuclease.",2010 Sep 16,"['Morin, Benjamin', 'Coutard, Bruno', 'Lelke, Michaela', 'Ferron, François', 'Kerber, Romy', 'Jamal, Saïd', 'Frangeul, Antoine', 'Baronti, Cécile', 'Charrel, Rémi', 'de Lamballerie, Xavier', 'Vonrhein, Clemens', 'Lescar, Julien', 'Bricogne, Gérard', 'Günther, Stephan', 'Canard, Bruno']",PLoS Pathog,,,True
d7e90855b317646bba5751946a9a5e675ea90fdc,PMC,"Hospitalized adult patients with 2009 influenza A(H1N1) in Beijing, China: risk factors for hospital mortality",http://dx.doi.org/10.1186/1471-2334-10-256,PMC2941683,20799934,CC BY,"BACKGROUND: In April 2009, the pandemic influenza A(H1N1) virus emerged and spread globally. The objective of this study was to describe the independent risk factors for hospital mortality and the treatment effect of corticosteroids among patients with 2009 influenza A(H1N1) infection. METHODS: We retrospectively obtained clinical data of 155 adult patients with confirmed infection of 2009 influenza A(H1N1) in 23 hospitals in Beijing, China from October 1 to December 23, 2009. Risk factors for hospital mortality were identified with multivariate logistic regression analysis. RESULTS: Among the 155 patients, 90 (58.1%) were male, and mean age was 43.0 ± 18.6 years, and comorbidities were present in 81 (52.3%) patients. The most common organ dysfunctions included acute respiratory failure, altered mental status, septic shock, and acute renal failure. Oseltamivir was initiated in 125 patients (80.6%), only 16 patients received antiviral therapy within 48 hours after symptom onset. Fifty-two patients (33.5%) were treated with systemic corticosteroids, with a median daily dose of 80 mg. Twenty-seven patients (17.4%) died during hospital stay. Diabetes [odds ratio (OR) 8.830, 95% confidence interval [CI] 2.041 to 38.201, p = 0.004) and lactate dehydrogenase (LDH) level (OR 1.240, 95% CI 1.025 to 1.500, p = 0.027) were independent risk factors of hospital death, as were septic shock and altered mental status. Corticosteroids use was associated with a trend toward higher hospital mortality (OR 3.668, 95% CI 0.987 to 13.640, p = 0.052). CONCLUSIONS: Hospitalized patients with 2009 H1N1 influenza had relative poor outcome. The risk factors at hospitalization may help clinicians to identify the high-risk patients. In addition, corticosteroids use should not be regarded as routine pharmacologic therapy.",2010 Aug 27,"['Xi, Xiuming', 'Xu, Yuan', 'Jiang, Li', 'Li, Ang', 'Duan, Jie', 'Du, Bin']",BMC Infect Dis,,,True
8a0731d1284b815e6139b1a40a4cc1f3b68dd4f3,PMC,Genome3D: A viewer-model framework for integrating and visualizing multi-scale epigenomic information within a three-dimensional genome,http://dx.doi.org/10.1186/1471-2105-11-444,PMC2941692,20813045,CC BY,"BACKGROUND: New technologies are enabling the measurement of many types of genomic and epigenomic information at scales ranging from the atomic to nuclear. Much of this new data is increasingly structural in nature, and is often difficult to coordinate with other data sets. There is a legitimate need for integrating and visualizing these disparate data sets to reveal structural relationships not apparent when looking at these data in isolation. RESULTS: We have applied object-oriented technology to develop a downloadable visualization tool, Genome3D, for integrating and displaying epigenomic data within a prescribed three-dimensional physical model of the human genome. In order to integrate and visualize large volume of data, novel statistical and mathematical approaches have been developed to reduce the size of the data. To our knowledge, this is the first such tool developed that can visualize human genome in three-dimension. We describe here the major features of Genome3D and discuss our multi-scale data framework using a representative basic physical model. We then demonstrate many of the issues and benefits of multi-resolution data integration. CONCLUSIONS: Genome3D is a software visualization tool that explores a wide range of structural genomic and epigenetic data. Data from various sources of differing scales can be integrated within a hierarchical framework that is easily adapted to new developments concerning the structure of the physical genome. In addition, our tool has a simple annotation mechanism to incorporate non-structural information. Genome3D is unique is its ability to manipulate large amounts of multi-resolution data from diverse sources to uncover complex and new structural relationships within the genome.",2010 Sep 2,"['Asbury, Thomas M', 'Mitman, Matt', 'Tang, Jijun', 'Zheng, W Jim']",BMC Bioinformatics,,,True
1d14fd3be698da4aa12b91523c9d099f76775604,PMC,Modulation of polymorphonuclear neutrophil functions by astrocytes,http://dx.doi.org/10.1186/1742-2094-7-53,PMC2942816,20828397,CC BY,"BACKGROUND: Neuroinflammation is a complex process involving cells from the immune system and the central nerve system (CNS). Polymorphonuclear neutrophils (PMN) are the most abundant class of white blood cells, and typically the first type of leukocyte recruited to sites of inflammation. In the CNS, astrocytes are the most abundant glial cell population and participate in the local innate immune response triggered by a variety of insults. In the present study, we investigated the impacts of astrocytes on PMN function. METHODS: Primary astrocyte cultures were derived from postnatal C57BL/6 mice and primary neutrophils were isolated from 8 to 12 weeks old C57BL/6 mice. PMNs respiratory burst was analyzed by H2DCFDA assay. For phagocytosis assay, neutrophils were incubated with FITC-labeled E. coli and the phagocytosis of E coli was determined by flow cytometer. PMNs degranulation was determined by myeloperoxidase assay. Cytokine expression was determined by real-time PCR. To determine the involvement of different signaling pathway, protein lysates were prepared and western blots were conducted to assess the activation of Akt, Erk1/2, and p38. RESULTS: Using ex vivo neutrophils and primary astrocyte cultures, our study demonstrated that astrocytes differentially regulate neutrophil functions, depending upon whether the interactions between the two cell types are direct or indirect. Upon direct cell-cell contact, astrocytes attenuate neutrophil apoptosis, respiratory bust, and degranulation, while enhancing neutrophil phagocytic capability and pro-inflammatory cytokine expression. Through indirect interaction with neutrophils, astrocytes attenuate apoptosis and enhance necrosis in neutrophils, augment neutrophil phagocytosis and respiratory burst, and inhibit neutrophil degranulation. In addition, astrocytes could augment Akt, Erk1/2, and p38 activation in neutrophils. CONCLUSIONS: Astrocytes differentially regulate neutrophil functions through direct or indirect interactions between the two cell types. The diversified actions of astrocytes on neutrophils might provide protection against potential microbial infections given compromised blood-brain barrier integrity under certain neuropathological conditions. The complex actions of astrocytes on neutrophils could provide further insight to harness the inflammatory response to promote CNS repair.",2010 Sep 9,"['Xie, Luokun', 'Poteet, Ethan C', 'Li, Wenjun', 'Scott, Amanda E', 'Liu, Ran', 'Wen, Yi', 'Ghorpade, Anuja', 'Simpkins, James W', 'Yang, Shao-Hua']",J Neuroinflammation,,,True
1c363c20418dda4f6c674f6d7af16f92b5dce974,PMC,Q&A: Antibiotic resistance: where does it come from and what can we do about it?,http://dx.doi.org/10.1186/1741-7007-8-123,PMC2942819,20887638,CC BY,,2010 Sep 20,"Wright, Gerard D",BMC Biol,,,True
59e3592ad1516fe1b4f4a1ea5a8cae320af5cf7d,PMC,"VIGOR, an annotation program for small viral genomes",http://dx.doi.org/10.1186/1471-2105-11-451,PMC2942859,20822531,CC BY,"BACKGROUND: The decrease in cost for sequencing and improvement in technologies has made it easier and more common for the re-sequencing of large genomes as well as parallel sequencing of small genomes. It is possible to completely sequence a small genome within days and this increases the number of publicly available genomes. Among the types of genomes being rapidly sequenced are those of microbial and viral genomes responsible for infectious diseases. However, accurate gene prediction is a challenge that persists for decoding a newly sequenced genome. Therefore, accurate and efficient gene prediction programs are highly desired for rapid and cost effective surveillance of RNA viruses through full genome sequencing. RESULTS: We have developed VIGOR (Viral Genome ORF Reader), a web application tool for gene prediction in influenza virus, rotavirus, rhinovirus and coronavirus subtypes. VIGOR detects protein coding regions based on sequence similarity searches and can accurately detect genome specific features such as frame shifts, overlapping genes, embedded genes, and can predict mature peptides within the context of a single polypeptide open reading frame. Genotyping capability for influenza and rotavirus is built into the program. We compared VIGOR to previously described gene prediction programs, ZCURVE_V, GeneMarkS and FLAN. The specificity and sensitivity of VIGOR are greater than 99% for the RNA viral genomes tested. CONCLUSIONS: VIGOR is a user friendly web-based genome annotation program for five different viral agents, influenza, rotavirus, rhinovirus, coronavirus and SARS coronavirus. This is the first gene prediction program for rotavirus and rhinovirus for public access. VIGOR is able to accurately predict protein coding genes for the above five viral types and has the capability to assign function to the predicted open reading frames and genotype influenza virus. The prediction software was designed for performing high throughput annotation and closure validation in a post-sequencing production pipeline.",2010 Sep 7,"['Wang, Shiliang', 'Sundaram, Jaideep P', 'Spiro, David']",BMC Bioinformatics,,,True
0ce2f11a7c4da992b9a8686bd3b2ed53064a2ac8,PMC,Ambient Influenza and Avian Influenza Virus during Dust Storm Days and Background Days,http://dx.doi.org/10.1289/ehp.0901782,PMC2944079,20435545,CC0,"BACKGROUND: The spread of influenza and highly pathogenic avian influenza (H5N1) presents a significant threat to human health. Avian influenza outbreaks in downwind areas of Asian dust storms (ADS) suggest that viruses might be transported by dust storms. OBJECTIVES: We developed a technique to measure ambient influenza and avian influenza viruses. We then used this technique to measure concentrations of these viruses on ADS days and background days, and to assess the relationships between ambient influenza and avian influenza viruses, and air pollutants. METHODS: A high-volume air sampler was used in parallel with a filter cassette to evaluate spiked samples and unspiked samples. Then, air samples were monitored during ADS seasons using a filter cassette coupled with a real-time quantitative polymerase chain reaction (qPCR) assay. Air samples were monitored during ADS season (1 January to 31 May 2006). RESULTS: We successfully quantified ambient influenza virus using the filtration/real-time qPCR method during ADS days and background days. To our knowledge, this is the first report describing the concentration of influenza virus in ambient air. In both the spiked and unspiked samples, the concentration of influenza virus sampled using the filter cassette was higher than that using the high-volume sampler. The concentration of ambient influenza A virus was significantly higher during the ADS days than during the background days. CONCLUSIONS: Our data imply the possibility of long-range transport of influenza virus.",2010 Sep 30,"['Chen, Pei-Shih', 'Tsai, Feng Ta', 'Lin, Chien Kun', 'Yang, Chun-Yuh', 'Chan, Chang-Chuan', 'Young, Chea-Yuan', 'Lee, Chien-Hung']",Environ Health Perspect,,,True
a776acb66d26bc9ad550cb9909e0f1ef35b57fec,PMC,Phylogenetic history demonstrates two different lineages of dengue type 1 virus in Colombia,http://dx.doi.org/10.1186/1743-422X-7-226,PMC2944171,20836894,CC BY,"BACKGROUND: Dengue Fever is one of the most important viral re-emergent diseases affecting about 50 million people around the world especially in tropical and sub-tropical countries. In Colombia, the virus was first detected in the earliest 70's when the disease became a major public health concern. Since then, all four serotypes of the virus have been reported. Although most of the huge outbreaks reported in this country have involved dengue virus serotype 1 (DENV-1), there are not studies about its origin, genetic diversity and distribution. RESULTS: We used 224 bp corresponding to the carboxyl terminus of envelope (E) gene from 74 Colombian isolates in order to reconstruct phylogenetic relationships and to estimate time divergences. Analyzed DENV-1 Colombian isolates belonged to the formerly defined genotype V. Only one virus isolate was clasified in the genotype I, likely representing a sole introduction that did not spread. The oldest strains were closely related to those detected for the first time in America in 1977 from the Caribbean and were detected for two years until their disappearance about six years later. Around 1987, a split up generated 2 lineages that have been evolving separately, although not major aminoacid changes in the analyzed region were found. CONCLUSION: DENV-1 has been circulating since 1978 in Colombia. Yet, the phylogenetic relationships between strains isolated along the covered period of time suggests that viral strains detected in some years, although belonging to the same genotype V, have different recent origins corresponding to multiple re-introduction events of viral strains that were circulating in neighbor countries. Viral strains used in the present study did not form a monophyletic group, which is evidence of a polyphyletic origin. We report the rapid spread patterns and high evolution rate of the different DENV-1 lineages.",2010 Sep 14,"['Mendez, Jairo A', 'Usme-Ciro, Jose A', 'Domingo, Cristina', 'Rey, Gloria J', 'Sanchez, Juan A', 'Tenorio, Antonio', 'Gallego-Gomez, Juan C']",Virol J,,,True
ac14252dbac614e01fef29b981cd841aa223f28e,PMC,Sequential introduction of single room isolation and hand hygiene campaign in the control of methicillin-resistant Staphylococcus aureus in intensive care unit,http://dx.doi.org/10.1186/1471-2334-10-263,PMC2944349,20822509,CC BY,"BACKGROUND: After renovation of the adult intensive care unit (ICU) with installation of ten single rooms, an enhanced infection control program was conducted to control the spread of methicillin-resistant Staphylococcus aureus (MRSA) in our hospital. METHODS: Since the ICU renovation, all patients colonized or infected with MRSA were nursed in single rooms with contact precautions. The incidence of MRSA infection in the ICU was monitored during 3 different phases: the baseline period (phase 1); after ICU renovation (phase 2) and after implementation of a hand hygiene campaign with alcohol-based hand rub (phase 3). Patients infected with extended spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella species were chosen as controls because they were managed in open cubicles with standard precautions. RESULTS: Without a major change in bed occupancy rate, nursing workforce, or the protocol of environmental cleansing throughout the study period, a stepwise reduction in ICU onset nonbacteraemic MRSA infection was observed: from 3.54 (phase 1) to 2.26 (phase 2, p = 0.042) and 1.02 (phase 3, p = 0.006) per 1000-patient-days. ICU onset bacteraemic MRSA infection was significantly reduced from 1.94 (phase 1) to 0.9 (phase 2, p = 0.005) and 0.28 (phase 3, p = 0.021) per 1000-patient-days. Infection due to ESBL-producing organisms did not show a corresponding reduction. The usage density of broad-spectrum antibiotics and fluoroquinolones increased from phase 1 to 3. However a significant trend improvement of ICU onset MRSA infection by segmented regression analysis can only be demonstrated when comparison was made before and after the severe acute respiratory syndrome (SARS) epidemic. This suggests that the deaths of fellow healthcare workers from an occupational acquired infection had an overwhelming effect on their compliance with infection control measures. CONCLUSION: Provision of single room isolation facilities and promotion of hand hygiene practice are important. However compliance with infection control measures relies largely on a personal commitment, which may increase when personal safety is threatened.",2010 Sep 7,"['Cheng, Vincent CC', 'Tai, Josepha WM', 'Chan, WM', 'Lau, Eric HY', 'Chan, Jasper FW', 'To, Kelvin KW', 'Li, Iris WS', 'Ho, PL', 'Yuen, KY']",BMC Infect Dis,,,True
e077bb756a7a9e4df0cdcc18f2e1cd509e4a3993,PMC,Evolutionary Entropy Determines Invasion Success in Emergent Epidemics,http://dx.doi.org/10.1371/journal.pone.0012951,PMC2944876,20886082,CC BY,"BACKGROUND: Standard epidemiological theory claims that in structured populations competition between multiple pathogen strains is a deterministic process which is mediated by the basic reproduction number ([Image: see text]) of the individual strains. A new theory based on analysis, simulation and empirical study challenges this predictor of success. PRINCIPAL FINDINGS: We show that the quantity [Image: see text] is a valid predictor in structured populations only when size is infinite. In this article we show that when population size is finite the dynamics of infection by multi-strain pathogens is a stochastic process whose outcome can be predicted by evolutionary entropy, S, an information theoretic measure which describes the uncertainty in the infectious age of an infected parent of a randomly chosen new infective. Evolutionary entropy characterises the demographic stability or robustness of the population of infectives. This statistical parameter determines the duration of infection and thus provides a quantitative index of the pathogenicity of a strain. Standard epidemiological theory based on [Image: see text] as a measure of selective advantage is the limit as the population size tends to infinity of the entropic selection theory. The standard model is an approximation to the entropic selection theory whose validity increases with population size. CONCLUSION: An epidemiological analysis based on entropy is shown to explain empirical observations regarding the emergence of less pathogenic strains of human influenza during the antigenic drift phase. Furthermore, we exploit the entropy perspective to discuss certain epidemiological patterns of the current H1N1 swine 'flu outbreak.",2010 Sep 23,"['Rhodes, Christopher J.', 'Demetrius, Lloyd']",PLoS One,,,True
a25045aa52c78b89840287b2cff9d7dffe0bb07f,PMC,The Nature of Protein Domain Evolution: Shaping the Interaction Network,http://dx.doi.org/10.2174/138920210791616725,PMC2945003,21286315,CC BY,"The proteomes that make up the collection of proteins in contemporary organisms evolved through recombination and duplication of a limited set of domains. These protein domains are essentially the main components of globular proteins and are the most principal level at which protein function and protein interactions can be understood. An important aspect of domain evolution is their atomic structure and biochemical function, which are both specified by the information in the amino acid sequence. Changes in this information may bring about new folds, functions and protein architectures. With the present and still increasing wealth of sequences and annotation data brought about by genomics, new evolutionary relationships are constantly being revealed, unknown structures modeled and phylogenies inferred. Such investigations not only help predict the function of newly discovered proteins, but also assist in mapping unforeseen pathways of evolution and reveal crucial, co-evolving inter- and intra-molecular interactions. In turn this will help us describe how protein domains shaped cellular interaction networks and the dynamics with which they are regulated in the cell. Additionally, these studies can be used for the design of new and optimized protein domains for therapy. In this review, we aim to describe the basic concepts of protein domain evolution and illustrate recent developments in molecular evolution that have provided valuable new insights in the field of comparative genomics and protein interaction networks.",2010 Aug,"['Bagowski, Christoph P', 'Bruins, Wouter', 'te Velthuis, Aartjan J.W']",Curr Genomics,,,True
9752210c4ae3a172559d5d7b3df9575e26b7359c,PMC,Pandemic influenza control in Europe and the constraints resulting from incoherent public health laws,http://dx.doi.org/10.1186/1471-2458-10-532,PMC2945945,20815888,CC BY,"BACKGROUND: With the emergence of influenza H1N1v the world is facing its first 21(st )century global pandemic. Severe Acute Respiratory Syndrome (SARS) and avian influenza H5N1 prompted development of pandemic preparedness plans. National systems of public health law are essential for public health stewardship and for the implementation of public health policy[1]. International coherence will contribute to effective regional and global responses. However little research has been undertaken on how law works as a tool for disease control in Europe. With co-funding from the European Union, we investigated the extent to which laws across Europe support or constrain pandemic preparedness planning, and whether national differences are likely to constrain control efforts. METHODS: We undertook a survey of national public health laws across 32 European states using a questionnaire designed around a disease scenario based on pandemic influenza. Questionnaire results were reviewed in workshops, analysing how differences between national laws might support or hinder regional responses to pandemic influenza. Respondents examined the impact of national laws on the movements of information, goods, services and people across borders in a time of pandemic, the capacity for surveillance, case detection, case management and community control, the deployment of strategies of prevention, containment, mitigation and recovery and the identification of commonalities and disconnects across states. RESULTS: Results of this study show differences across Europe in the extent to which national pandemic policy and pandemic plans have been integrated with public health laws. We found significant differences in legislation and in the legitimacy of strategic plans. States differ in the range and the nature of intervention measures authorized by law, the extent to which borders could be closed to movement of persons and goods during a pandemic, and access to healthcare of non-resident persons. Some states propose use of emergency powers that might potentially override human rights protections while other states propose to limit interventions to those authorized by public health laws. CONCLUSION: These differences could create problems for European strategies if an evolving influenza pandemic results in more serious public health challenges or, indeed, if a novel disease other than influenza emerges with pandemic potential. There is insufficient understanding across Europe of the role and importance of law in pandemic planning. States need to build capacity in public health law to support disease prevention and control policies. Our research suggests that states would welcome further guidance from the EU on management of a pandemic, and guidance to assist in greater commonality of legal approaches across states.",2010 Sep 3,"['Martin, Robyn', 'Conseil, Alexandra', 'Longstaff, Abie', 'Kodo, Jimmy', 'Siegert, Joachim', 'Duguet, Anne-Marie', 'Lobato de Faria, Paula', 'Haringhuizen, George', 'Espin, Jaime', 'Coker, Richard']",BMC Public Health,,,True
9fb2d27c92ebc1fc7804e55e557fe8c126da62f9,PMC,Respiratory Syncytial Virus (RSV) RNA loads in peripheral blood correlates with disease severity in mice,http://dx.doi.org/10.1186/1465-9921-11-125,PMC2946301,20843364,CC BY,"BACKGROUND: Respiratory Syncytial Virus (RSV) infection is usually restricted to the respiratory epithelium. Few studies have documented the presence of RSV in the systemic circulation, however there is no consistent information whether virus detection in the blood correlates with disease severity. METHODS: Balb/c mice were inoculated with live RSV, heat-inactivated RSV or medium. A subset of RSV-infected mice was treated with anti-RSV antibody 72 h post-inoculation. RSV RNA loads were measured by PCR in peripheral blood from day 1-21 post-inoculation and were correlated with upper and lower respiratory tract viral loads, the systemic cytokine response, lung inflammation and pulmonary function. Immunohistochemical staining was used to define the localization of RSV antigens in the respiratory tract and peripheral blood. RESULTS: RSV RNA loads were detected in peripheral blood from day 1 to 14 post-inoculation, peaked on day 5 and significantly correlated with nasal and lung RSV loads, airway obstruction, and blood CCL2 and CXCL1 expression. Treatment with anti-RSV antibody reduced blood RSV RNA loads and improved airway obstruction. Immunostaining identified RSV antigens in alveolar macrophages and peripheral blood monocytes. CONCLUSIONS: RSV RNA was detected in peripheral blood upon infection with live RSV, followed a time-course parallel to viral loads assessed in the respiratory tract and was significantly correlated with RSV-induced airway disease.",2010 Sep 15,"['Torres, Juan Pablo', 'Gomez, Ana M', 'Khokhar, Shama', 'Bhoj, Vijay G', 'Tagliabue, Claudia', 'Chang, Michael L', 'Kiener, Peter A', 'Revell, Paula A', 'Ramilo, Octavio', 'Mejias, Asuncion']",Respir Res,,,True
e45e16034a3ab42bfce64e2b6886604a57974091,PMC,Quantitative Phosphoproteomics of Proteasome Inhibition in Multiple Myeloma Cells,http://dx.doi.org/10.1371/journal.pone.0013095,PMC2947515,20927383,CC BY,"BACKGROUND: The proteasome inhibitor bortezomib represents an important advance in the treatment of multiple myeloma (MM). Bortezomib inhibits the activity of the 26S proteasome and induces cell death in a variety of tumor cells; however, the mechanism of cytotoxicity is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the differential phosphoproteome upon proteasome inhibition by using stable isotope labeling by amino acids in cell culture (SILAC) in combination with phosphoprotein enrichment and LC-MS/MS analysis. In total 233 phosphoproteins were identified and 72 phosphoproteins showed a 1.5-fold or greater change upon bortezomib treatment. The phosphoproteins with expression alterations encompass all major protein classes, including a large number of nucleic acid binding proteins. Site-specific phosphopeptide quantitation revealed that Ser38 phosphorylation on stathmin increased upon bortezomib treatment, suggesting new mechanisms associated to bortezomib-induced apoptosis in MM cells. Further studies demonstrated that stathmin phosphorylation profile was modified in response to bortezomib treatment and the regulation of stathmin by phosphorylation at specific Ser/Thr residues participated in the cellular response induced by bortezomib. CONCLUSIONS/SIGNIFICANCE: Our systematic profiling of phosphorylation changes in response to bortezomib treatment not only advanced the global mechanistic understanding of the action of bortezomib on myeloma cells but also identified previously uncharacterized signaling proteins in myeloma cells.",2010 Sep 29,"['Ge, Feng', 'Xiao, Chuan-Le', 'Bi, Li-Jun', 'Tao, Sheng-Ce', 'Xiong, Sheng', 'Yin, Xin-Feng', 'Li, Li-Ping', 'Lu, Chun-Hua', 'Jia, Hai-Tao', 'He, Qing-Yu']",PLoS One,,,True
303dd57924047b30670081699eb8c991bf0f41b5,PMC,Insights into the Evolution and Emergence of a Novel Infectious Disease,http://dx.doi.org/10.1371/journal.pcbi.1000947,PMC2947978,20941384,CC BY,"Many zoonotic, novel infectious diseases in humans appear as sporadic infections with spatially and temporally restricted outbreaks, as seen with influenza A(H5N1). Adaptation is often a key factor for successfully establishing sustained human-to-human transmission. Here we use simple mathematical models to describe different adaptation scenarios with particular reference to spatial heterogeneity within the human population. We present analytical expressions for the probability of emergence per introduction, as well as the waiting time to a successful emergence event. Furthermore, we derive general analytical results for the statistical properties of emergence events, including the probability distribution of outbreak sizes. We compare our analytical results with a stochastic model, which has previously been studied computationally. Our results suggest that, for typical connection strengths between communities, spatial heterogeneity has only a weak effect on outbreak size distributions, and on the risk of emergence per introduction. For example, if [Image: see text] or larger, any village connected to a large city by just ten commuters a day is, effectively, just a part of the city when considering the chances of emergence and the outbreak size distribution. We present empirical data on commuting patterns and show that the vast majority of communities for which such data are available are at least this well interconnected. For plausible parameter ranges, the effects of spatial heterogeneity are likely to be dominated by the evolutionary biology of host adaptation. We conclude by discussing implications for surveillance and control of emerging infections.",2010 Sep 30,"['Kubiak, Ruben J.', 'Arinaminpathy, Nimalan', 'McLean, Angela R.']",PLoS Comput Biol,,,True
41fe2339a1ad28cdcaff3e45b41c4cbd05a0b163,PMC,Insights into the Evolution and Emergence of a Novel Infectious Disease,http://dx.doi.org/10.1371/journal.pcbi.1000947,PMC2947978,20941384,CC BY,"Many zoonotic, novel infectious diseases in humans appear as sporadic infections with spatially and temporally restricted outbreaks, as seen with influenza A(H5N1). Adaptation is often a key factor for successfully establishing sustained human-to-human transmission. Here we use simple mathematical models to describe different adaptation scenarios with particular reference to spatial heterogeneity within the human population. We present analytical expressions for the probability of emergence per introduction, as well as the waiting time to a successful emergence event. Furthermore, we derive general analytical results for the statistical properties of emergence events, including the probability distribution of outbreak sizes. We compare our analytical results with a stochastic model, which has previously been studied computationally. Our results suggest that, for typical connection strengths between communities, spatial heterogeneity has only a weak effect on outbreak size distributions, and on the risk of emergence per introduction. For example, if [Image: see text] or larger, any village connected to a large city by just ten commuters a day is, effectively, just a part of the city when considering the chances of emergence and the outbreak size distribution. We present empirical data on commuting patterns and show that the vast majority of communities for which such data are available are at least this well interconnected. For plausible parameter ranges, the effects of spatial heterogeneity are likely to be dominated by the evolutionary biology of host adaptation. We conclude by discussing implications for surveillance and control of emerging infections.",2010 Sep 30,"['Kubiak, Ruben J.', 'Arinaminpathy, Nimalan', 'McLean, Angela R.']",PLoS Comput Biol,,,False
50e55ab8dd87f7523b7f25203ef10004c8d3b13e,PMC,Role of Host Immune Response and Viral Load in the Differential Outcome of Pandemic H1N1 (2009) Influenza Virus Infection in Indian Patients,http://dx.doi.org/10.1371/journal.pone.0013099,PMC2948498,20957032,CC BY,"BACKGROUND: An unusually high number of severe pneumonia cases with considerable mortality is being observed with the pandemic H1N1 2009 virus infections globally. In India, all mild as well as critically ill cases were admitted and treated in the government hospitals during the initial phase of the pandemic. The present study was undertaken during this early phase of the pandemic. METHODOLOGY: The role of viral load and host factors in the pathogenesis were assessed by examining 26 mild (MP), 15 critically ill patients (CIP) and 20 healthy controls from Pune, India. Sequential blood and lung aspirate samples were collected from CIP. Viral load and cytokines/chemokine levels were determined from the plasma and lung aspirates of the patients. TLR levels were determined by staining and FACS analysis. Gene profiling was done for both cells in the lung aspirates and PBMCs using TaqMan Low Density arrays. Antibody titres and isotyping was done using HA protein based ELISAs. PRINCIPAL FINDINGS: 13/15 critically ill patients expired. All plasma samples were negative for the virus irrespective of the patient's category. Sequential lung samples from CIP showed lower viral loads questioning association of viral replication with the severity. Anti-rpH1N1-09-HA-IgG titres were significantly higher in critically ill patients and both categories circulated exclusively IgG1 isotype. Critically ill patients exhibited increase in TLR-3, 4, 7 and decrease in TLR-2 expressions. The disease severity correlated with increased plasma levels of IL1RA, IL2, IL6, CCL3, CCL4 and IL10. Majority of the immune-function genes were down-regulated in the PBMCs and up-regulated in the cells from lung aspirates of critically ill patients. No distinct pattern differentiating fatal and surviving patients was observed when sequential samples were examined for various parameters. CONCLUSIONS: Disease severity was associated with pronounced impairment of host immune response.",2010 Oct 1,"['Arankalle, Vidya A.', 'Lole, Kavita S.', 'Arya, Ravi P.', 'Tripathy, Anuradha S.', 'Ramdasi, Ashwini Y.', 'Chadha, Mandeep S.', 'Sangle, Shashi A.', 'Kadam, Deelip B.']",PLoS One,,,True
69a50ad03d5fb9a5129663062a9b718217b62665,PMC,Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated “Human Immune System” Mice,http://dx.doi.org/10.1371/journal.pone.0013137,PMC2949385,20957227,CC BY,"BACKGROUND: Passive transfer of antibodies not only provides immediate short-term protection against disease, but also can be exploited as a therapeutic tool. However, the ‘humanization’ of murine monoclonal antibodies (mAbs) is a time-consuming and expensive process that has the inherent drawback of potentially altering antigenic specificity and/or affinity. The immortalization of human B cells represents an alternative for obtaining human mAbs, but relies on the availability of biological samples from vaccinated individuals or convalescent patients. In this work we describe a novel approach to generate fully human mAbs by combining a humanized mouse model with a new B cell immortalization technique. METHODOLOGY/PRINCIPAL FINDINGS: After transplantation with CD34(+)CD38(−) human hematopoietic progenitor cells, BALB/c Rag2(−/−)IL-2Rγc(−/−) mice acquire a human immune system and harbor B cells with a diverse IgM repertoire. “Human Immune System” mice were then immunized with two commercial vaccine antigens, tetanus toxoid and hepatitis B surface antigen. Sorted human CD19(+)CD27(+) B cells were retrovirally transduced with the human B cell lymphoma (BCL)-6 and BCL-XL genes, and subsequently cultured in the presence of CD40-ligand and IL-21. This procedure allows generating stable B cell receptor-positive B cells that secrete immunoglobulins. We recovered stable B cell clones that produced IgM specific for tetanus toxoid and the hepatitis B surface antigen, respectively. CONCLUSION/SIGNIFICANCE: This work provides the proof-of-concept for the usefulness of this novel method based on the immunization of humanized mice for the rapid generation of human mAbs against a wide range of antigens.",2010 Oct 4,"['Becker, Pablo D.', 'Legrand, Nicolas', 'van Geelen, Caroline M. M.', 'Noerder, Miriam', 'Huntington, Nicholas D.', 'Lim, Annick', 'Yasuda, Etsuko', 'Diehl, Sean A.', 'Scheeren, Ferenc A.', 'Ott, Michael', 'Weijer, Kees', 'Wedemeyer, Heiner', 'Di Santo, James P.', 'Beaumont, Tim', 'Guzman, Carlos A.', 'Spits, Hergen']",PLoS One,,,True
bde7fe0594a0902867cbde6e9271090f7f5fe9ac,PMC,Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated “Human Immune System” Mice,http://dx.doi.org/10.1371/journal.pone.0013137,PMC2949385,20957227,CC BY,"BACKGROUND: Passive transfer of antibodies not only provides immediate short-term protection against disease, but also can be exploited as a therapeutic tool. However, the ‘humanization’ of murine monoclonal antibodies (mAbs) is a time-consuming and expensive process that has the inherent drawback of potentially altering antigenic specificity and/or affinity. The immortalization of human B cells represents an alternative for obtaining human mAbs, but relies on the availability of biological samples from vaccinated individuals or convalescent patients. In this work we describe a novel approach to generate fully human mAbs by combining a humanized mouse model with a new B cell immortalization technique. METHODOLOGY/PRINCIPAL FINDINGS: After transplantation with CD34(+)CD38(−) human hematopoietic progenitor cells, BALB/c Rag2(−/−)IL-2Rγc(−/−) mice acquire a human immune system and harbor B cells with a diverse IgM repertoire. “Human Immune System” mice were then immunized with two commercial vaccine antigens, tetanus toxoid and hepatitis B surface antigen. Sorted human CD19(+)CD27(+) B cells were retrovirally transduced with the human B cell lymphoma (BCL)-6 and BCL-XL genes, and subsequently cultured in the presence of CD40-ligand and IL-21. This procedure allows generating stable B cell receptor-positive B cells that secrete immunoglobulins. We recovered stable B cell clones that produced IgM specific for tetanus toxoid and the hepatitis B surface antigen, respectively. CONCLUSION/SIGNIFICANCE: This work provides the proof-of-concept for the usefulness of this novel method based on the immunization of humanized mice for the rapid generation of human mAbs against a wide range of antigens.",2010 Oct 4,"['Becker, Pablo D.', 'Legrand, Nicolas', 'van Geelen, Caroline M. M.', 'Noerder, Miriam', 'Huntington, Nicholas D.', 'Lim, Annick', 'Yasuda, Etsuko', 'Diehl, Sean A.', 'Scheeren, Ferenc A.', 'Ott, Michael', 'Weijer, Kees', 'Wedemeyer, Heiner', 'Di Santo, James P.', 'Beaumont, Tim', 'Guzman, Carlos A.', 'Spits, Hergen']",PLoS One,,,False
51bc480cd0248cb14486d0c20a6693b032fd8043,PMC,Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated “Human Immune System” Mice,http://dx.doi.org/10.1371/journal.pone.0013137,PMC2949385,20957227,CC BY,"BACKGROUND: Passive transfer of antibodies not only provides immediate short-term protection against disease, but also can be exploited as a therapeutic tool. However, the ‘humanization’ of murine monoclonal antibodies (mAbs) is a time-consuming and expensive process that has the inherent drawback of potentially altering antigenic specificity and/or affinity. The immortalization of human B cells represents an alternative for obtaining human mAbs, but relies on the availability of biological samples from vaccinated individuals or convalescent patients. In this work we describe a novel approach to generate fully human mAbs by combining a humanized mouse model with a new B cell immortalization technique. METHODOLOGY/PRINCIPAL FINDINGS: After transplantation with CD34(+)CD38(−) human hematopoietic progenitor cells, BALB/c Rag2(−/−)IL-2Rγc(−/−) mice acquire a human immune system and harbor B cells with a diverse IgM repertoire. “Human Immune System” mice were then immunized with two commercial vaccine antigens, tetanus toxoid and hepatitis B surface antigen. Sorted human CD19(+)CD27(+) B cells were retrovirally transduced with the human B cell lymphoma (BCL)-6 and BCL-XL genes, and subsequently cultured in the presence of CD40-ligand and IL-21. This procedure allows generating stable B cell receptor-positive B cells that secrete immunoglobulins. We recovered stable B cell clones that produced IgM specific for tetanus toxoid and the hepatitis B surface antigen, respectively. CONCLUSION/SIGNIFICANCE: This work provides the proof-of-concept for the usefulness of this novel method based on the immunization of humanized mice for the rapid generation of human mAbs against a wide range of antigens.",2010 Oct 4,"['Becker, Pablo D.', 'Legrand, Nicolas', 'van Geelen, Caroline M. M.', 'Noerder, Miriam', 'Huntington, Nicholas D.', 'Lim, Annick', 'Yasuda, Etsuko', 'Diehl, Sean A.', 'Scheeren, Ferenc A.', 'Ott, Michael', 'Weijer, Kees', 'Wedemeyer, Heiner', 'Di Santo, James P.', 'Beaumont, Tim', 'Guzman, Carlos A.', 'Spits, Hergen']",PLoS One,,,False
cf665ea806b5a1b271c377e3826bf9d8bd0ebf9f,PMC,Profiling of cellular proteins in porcine reproductive and respiratory syndrome virus virions by proteomics analysis,http://dx.doi.org/10.1186/1743-422X-7-242,PMC2949843,20849641,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped virus, bearing severe economic consequences to the swine industry worldwide. Previous studies on enveloped viruses have shown that many incorporated cellular proteins associated with the virion's membranes that might play important roles in viral infectivity. In this study, we sought to proteomically profile the cellular proteins incorporated into or associated with the virions of a highly virulent PRRSV strain GDBY1, and to provide foundation for further investigations on the roles of incorporated/associated cellular proteins on PRRSV's infectivity. RESULTS: In our experiment, sixty one cellular proteins were identified in highly purified PRRSV virions by two-dimensional gel electrophoresis coupled with mass spectrometric approaches. The identified cellular proteins could be grouped into eight functional categories including cytoskeletal proteins, chaperones, macromolecular biosynthesis proteins, metabolism-associated proteins, calcium-dependent membrane-binding proteins and other functional proteins. Among the identified proteins, four have not yet been reported in other studied envelope viruses, namely, guanine nucleotide-binding proteins, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase, peroxiredoxin 1 and galectin-1 protein. The presence of five selected cellular proteins (i.e., β-actin, Tubulin, Annexin A2, heat shock protein Hsp27, and calcium binding proteins S100) in the highly purified PRRSV virions was validated by Western blot and immunogold labeling assays. CONCLUSIONS: Taken together, the present study has demonstrated the incorporation of cellular proteins in PRRSV virions, which provides valuable information for the further investigations for the effects of individual cellular proteins on the viral replication, assembly, and pathogenesis.",2010 Sep 18,"['Zhang, Chengwen', 'Xue, Chunyi', 'Li, Yan', 'Kong, Qingming', 'Ren, Xiangpeng', 'Li, Xiaoming', 'Shu, Dingming', 'Bi, Yingzuo', 'Cao, Yongchang']",Virol J,,,True
d15737a61bc7a5c77a10ff81579ab5ffcaab4393,PMC,Selective gene silencing by viral delivery of short hairpin RNA,http://dx.doi.org/10.1186/1743-422X-7-248,PMC2949849,20858246,CC BY,"RNA interference (RNAi) technology has not only become a powerful tool for functional genomics, but also allows rapid drug target discovery and in vitro validation of these targets in cell culture. Furthermore, RNAi represents a promising novel therapeutic option for treating human diseases, in particular cancer. Selective gene silencing by RNAi can be achieved essentially by two nucleic acid based methods: i) cytoplasmic delivery of short double-stranded (ds) interfering RNA oligonucleotides (siRNA), where the gene silencing effect is only transient in nature, and possibly not suitable for all applications; or ii) nuclear delivery of gene expression cassettes that express short hairpin RNA (shRNA), which are processed like endogenous interfering RNA and lead to stable gene down-regulation. Both processes involve the use of nucleic acid based drugs, which are highly charged and do not cross cell membranes by free diffusion. Therefore, in vivo delivery of RNAi therapeutics must use technology that enables the RNAi therapeutic to traverse biological membrane barriers in vivo. Viruses and the vectors derived from them carry out precisely this task and have become a major delivery system for shRNA. Here, we summarize and compare different currently used viral delivery systems, give examples of in vivo applications, and indicate trends for new developments, such as replicating viruses for shRNA delivery to cancer cells.",2010 Sep 21,"['Sliva, Katja', 'Schnierle, Barbara S']",Virol J,,,True
37485356ce87c19f6d32121ed6b64b28c3041c24,PMC,Reflections on Pandemic (H1N1) 2009 and the International Response,http://dx.doi.org/10.1371/journal.pmed.1000346,PMC2950129,20957189,CC BY,"Gabriel Leung and Angus Nicoll provide their reflections on the international response to the 2009 H1N1 influenza pandemic, including what went well and what changes need to be made in anticipation of future flu pandemics.",2010 Oct 5,"['Leung, Gabriel M.', 'Nicoll, Angus']",PLoS Med,,,True
e86b3861c3d400a8a5baf860545af22254fc9c0b,PMC,Profiling of Substrate Specificity of SARS-CoV 3CL(pro),http://dx.doi.org/10.1371/journal.pone.0013197,PMC2950840,20949131,CC BY,"BACKGROUND: The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome-coronavirus is required for autoprocessing of the polyprotein, and is a potential target for treating coronaviral infection. METHODOLOGY/PRINCIPAL FINDINGS: To obtain a thorough understanding of substrate specificity of the protease, a substrate library of 19[Image: see text]8 variants was created by performing saturation mutagenesis on the autocleavage sequence at P5 to P3' positions. The substrate sequences were inserted between cyan and yellow fluorescent proteins so that the cleavage rates were monitored by in vitro fluorescence resonance energy transfer. The relative cleavage rate for different substrate sequences was correlated with various structural properties. P5 and P3 positions prefer residues with high β-sheet propensity; P4 prefers small hydrophobic residues; P2 prefers hydrophobic residues without β-branch. Gln is the best residue at P1 position, but observable cleavage can be detected with His and Met substitutions. P1' position prefers small residues, while P2' and P3' positions have no strong preference on residue substitutions. Noteworthy, solvent exposed sites such as P5, P3 and P3' positions favour positively charged residues over negatively charged one, suggesting that electrostatic interactions may play a role in catalysis. A super-active substrate, which combined the preferred residues at P5 to P1 positions, was found to have 2.8 fold higher activity than the wild-type sequence. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated a strong structure-activity relationship between the 3CL(pro) and its substrate. The substrate specificity profiled in this study may provide insights into a rational design of peptidomimetic inhibitors.",2010 Oct 6,"['Chuck, Chi-Pang', 'Chong, Lin-Tat', 'Chen, Chao', 'Chow, Hak-Fun', 'Wan, David Chi-Cheong', 'Wong, Kam-Bo']",PLoS One,,,True
28e355b80d2d62c5314e8d97e92fbd67f77679d5,PMC,A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case,http://dx.doi.org/10.1371/journal.pone.0013315,PMC2953511,20976271,CC BY,"Autopsy studies have shown that human highly pathogenic avian influenza virus (H5N1) can infect multiple human organs other than just the lungs, and that possible causes of organ damage are either viral replication and/or dysregulation of cytokines and chemokines. Uncertainty still exists, partly because of the limited number of cases analysed. In this study, a full autopsy including 5 organ systems was conducted on a confirmed H5N1 human fatal case (male, 42 years old) within 18 hours of death. In addition to the respiratory system (lungs, bronchus and trachea), virus was isolated from cerebral cortex, cerebral medullary substance, cerebellum, brain stem, hippocampus ileum, colon, rectum, ureter, aortopulmonary vessel and lymph-node. Real time RT-PCR evidence showed that matrix and hemagglutinin genes were positive in liver and spleen in addition to positive tissues with virus isolation. Immunohistochemistry and in-situ hybridization stains showed accordant evidence of viral infection with real time RT-PCR except bronchus. Quantitative RT-PCR suggested that a high viral load was associated with increased host responses, though the viral load was significantly different in various organs. Cells of the immunologic system could also be a target for virus infection. Overall, the pathogenesis of HPAI H5N1 virus was associated both with virus replication and with immunopathologic lesions. In addition, immune cells cannot be excluded from playing a role in dissemination of the virus in vivo.",2010 Oct 12,"['Gao, Rongbao', 'Dong, Libo', 'Dong, Jie', 'Wen, Leying', 'Zhang, Ye', 'Yu, Hongjie', 'Feng, Zijian', 'Chen, Minmei', 'Tan, Yi', 'Mo, Zhaojun', 'Liu, Haiyan', 'Fan, Yunyan', 'Li, Kunxiong', 'Li, Chris Ka-Fai', 'Li, Dexin', 'Yang, Weizhong', 'Shu, Yuelong']",PLoS One,,,True
b35c5f90e09d90f6fd6cff9dab355755e4c33fe4,PMC,Situational Awareness and Health Protective Responses to Pandemic Influenza A (H1N1) in Hong Kong: A Cross-Sectional Study,http://dx.doi.org/10.1371/journal.pone.0013350,PMC2953514,20967280,CC BY,"BACKGROUND: Whether information sources influence health protective behaviours during influenza pandemics or other emerging infectious disease epidemics is uncertain. METHODOLOGY: Data from cross-sectional telephone interviews of 1,001 Hong Kong adults in June, 2009 were tested against theory and data-derived hypothesized associations between trust in (formal/informal) information, understanding, self-efficacy, perceived susceptibility and worry, and hand hygiene and social distancing using Structural Equation Modelling with multigroup comparisons. PRINCIPAL FINDINGS: Trust in formal (government/media) information about influenza was associated with greater reported understanding of A/H1N1 cause (β = 0.36) and A/H1N1 prevention self-efficacy (β = 0.25), which in turn were associated with more hand hygiene (β = 0.19 and β = 0.23, respectively). Trust in informal (interpersonal) information was negatively associated with perceived personal A/H1N1 susceptibility (β = −0.21), which was negatively associated with perceived self-efficacy (β = −0.42) but positively associated with influenza worry (β = 0.44). Trust in informal information was positively associated with influenza worry (β = 0.16) which was in turn associated with greater social distancing (β = 0.36). Multigroup comparisons showed gender differences regarding paths from trust in formal information to understanding of A/H1N1 cause, trust in informal information to understanding of A/H1N1 cause, and understanding of A/H1N1 cause to perceived self-efficacy. CONCLUSIONS/SIGNIFICANCE: Trust in government/media information was more strongly associated with greater self-efficacy and handwashing, whereas trust in informal information was strongly associated with perceived health threat and avoidance behaviour. Risk communication should consider the effect of gender differences.",2010 Oct 12,"['Liao, Qiuyan', 'Cowling, Benjamin', 'Lam, Wing Tak', 'Ng, Man Wai', 'Fielding, Richard']",PLoS One,,,True
2d298d793c2521ceebdcd2c4be960591032ae0d3,PMC,Human Anti-Plague Monoclonal Antibodies Protect Mice from Yersinia pestis in a Bubonic Plague Model,http://dx.doi.org/10.1371/journal.pone.0013047,PMC2954148,20976274,CC0,"Yersinia pestis is the etiologic agent of plague that has killed more than 200 million people throughout the recorded history of mankind. Antibiotics may provide little immediate relief to patients who have a high bacteremia or to patients infected with an antibiotic resistant strain of plague. Two virulent factors of Y. pestis are the capsid F1 protein and the low-calcium response (Lcr) V-protein or V-antigen that have been proven to be the targets for both active and passive immunization. There are mouse monoclonal antibodies (mAbs) against the F1- and V-antigens that can passively protect mice in a murine model of plague; however, there are no anti-Yersinia pestis monoclonal antibodies available for prophylactic or therapeutic treatment in humans. We identified one anti-F1-specific human mAb (m252) and two anti-V-specific human mAb (m253, m254) by panning a naïve phage-displayed Fab library against the F1- and V-antigens. The Fabs were converted to IgG1s and their binding and protective activities were evaluated. M252 bound weakly to peptides located at the F1 N-terminus where a protective mouse anti-F1 mAb also binds. M253 bound strongly to a V-antigen peptide indicating a linear epitope; m254 did not bind to any peptide from a panel of 53 peptides suggesting that its epitope may be conformational. M252 showed better protection than m253 and m254 against a Y, pestis challenge in a plague mouse model. A synergistic effect was observed when the three antibodies were combined. Incomplete to complete protection was achieved when m252 was given at different times post-challenge. These antibodies can be further studied to determine their potential as therapeutics or prophylactics in Y. pestis infection in humans.",2010 Oct 13,"['Xiao, Xiaodong', 'Zhu, Zhongyu', 'Dankmeyer, Jennifer L.', 'Wormald, Michael M.', 'Fast, Randy L.', 'Worsham, Patricia L.', 'Cote, Christopher K.', 'Amemiya, Kei', 'Dimitrov, Dimiter S.']",PLoS One,,,True
311d15fee68d2a591ffc4e7cc0187b8dae872f9c,PMC,Combining Free Text and Structured Electronic Medical Record Entries to Detect Acute Respiratory Infections,http://dx.doi.org/10.1371/journal.pone.0013377,PMC2954790,20976281,CC BY,"BACKGROUND: The electronic medical record (EMR) contains a rich source of information that could be harnessed for epidemic surveillance. We asked if structured EMR data could be coupled with computerized processing of free-text clinical entries to enhance detection of acute respiratory infections (ARI). METHODOLOGY: A manual review of EMR records related to 15,377 outpatient visits uncovered 280 reference cases of ARI. We used logistic regression with backward elimination to determine which among candidate structured EMR parameters (diagnostic codes, vital signs and orders for tests, imaging and medications) contributed to the detection of those reference cases. We also developed a computerized free-text search to identify clinical notes documenting at least two non-negated ARI symptoms. We then used heuristics to build case-detection algorithms that best combined the retained structured EMR parameters with the results of the text analysis. PRINCIPAL FINDINGS: An adjusted grouping of diagnostic codes identified reference ARI patients with a sensitivity of 79%, a specificity of 96% and a positive predictive value (PPV) of 32%. Of the 21 additional structured clinical parameters considered, two contributed significantly to ARI detection: new prescriptions for cough remedies and elevations in body temperature to at least 38°C. Together with the diagnostic codes, these parameters increased detection sensitivity to 87%, but specificity and PPV declined to 95% and 25%, respectively. Adding text analysis increased sensitivity to 99%, but PPV dropped further to 14%. Algorithms that required satisfying both a query of structured EMR parameters as well as text analysis disclosed PPVs of 52–68% and retained sensitivities of 69–73%. CONCLUSION: Structured EMR parameters and free-text analyses can be combined into algorithms that can detect ARI cases with new levels of sensitivity or precision. These results highlight potential paths by which repurposed EMR information could facilitate the discovery of epidemics before they cause mass casualties.",2010 Oct 14,"['DeLisle, Sylvain', 'South, Brett', 'Anthony, Jill A.', 'Kalp, Ericka', 'Gundlapallli, Adi', 'Curriero, Frank C.', 'Glass, Greg E.', 'Samore, Matthew', 'Perl, Trish M.']",PLoS One,,,True
c05053ab5281d6f0329a0b2b124acf02fb5875b7,PMC,High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing,http://dx.doi.org/10.1371/journal.ppat.1001146,PMC2954836,20976195,CC0,"We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.",2010 Oct 14,"['Beitzel, Brett F.', 'Bakken, Russell R.', 'Smith, Jeffrey M.', 'Schmaljohn, Connie S.']",PLoS Pathog,,,True
4e9b9412e96583aaca4e9f9a305fd7444859c34b,PMC,High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing,http://dx.doi.org/10.1371/journal.ppat.1001146,PMC2954836,20976195,CC0,"We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.",2010 Oct 14,"['Beitzel, Brett F.', 'Bakken, Russell R.', 'Smith, Jeffrey M.', 'Schmaljohn, Connie S.']",PLoS Pathog,,,False
45b9123437117a4568919c5ef48cdad3bf5410cd,PMC,High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing,http://dx.doi.org/10.1371/journal.ppat.1001146,PMC2954836,20976195,CC0,"We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.",2010 Oct 14,"['Beitzel, Brett F.', 'Bakken, Russell R.', 'Smith, Jeffrey M.', 'Schmaljohn, Connie S.']",PLoS Pathog,,,False
7ad712a652dcfa7e01cf192177602296e1c5bf1a,PMC,High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing,http://dx.doi.org/10.1371/journal.ppat.1001146,PMC2954836,20976195,CC0,"We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.",2010 Oct 14,"['Beitzel, Brett F.', 'Bakken, Russell R.', 'Smith, Jeffrey M.', 'Schmaljohn, Connie S.']",PLoS Pathog,,,False
34a95c9d94919eaef9a5bb6a863cf75a41d8e10a,PMC,High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing,http://dx.doi.org/10.1371/journal.ppat.1001146,PMC2954836,20976195,CC0,"We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.",2010 Oct 14,"['Beitzel, Brett F.', 'Bakken, Russell R.', 'Smith, Jeffrey M.', 'Schmaljohn, Connie S.']",PLoS Pathog,,,False
e59cf9611fc13cb4b124e5677ba3290a3c6bf7d7,PMC,High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing,http://dx.doi.org/10.1371/journal.ppat.1001146,PMC2954836,20976195,CC0,"We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.",2010 Oct 14,"['Beitzel, Brett F.', 'Bakken, Russell R.', 'Smith, Jeffrey M.', 'Schmaljohn, Connie S.']",PLoS Pathog,,,False
7d07ea5145ff28047a49998617c8e015c5d19ece,PMC,High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing,http://dx.doi.org/10.1371/journal.ppat.1001146,PMC2954836,20976195,CC0,"We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system.",2010 Oct 14,"['Beitzel, Brett F.', 'Bakken, Russell R.', 'Smith, Jeffrey M.', 'Schmaljohn, Connie S.']",PLoS Pathog,,,False
13194f8e42df83d260e53ad9bf7448577e9319e5,PMC,Identification and characterization of a virus-specific continuous B-cell epitope on the PrM/M protein of Japanese Encephalitis Virus: potential application in the detection of antibodies to distinguish Japanese Encephalitis Virus infection from West Nile Virus and Dengue Virus infections,http://dx.doi.org/10.1186/1743-422X-7-249,PMC2954857,20858291,CC BY,"BACKGROUND: Differential diagnose of Japanese encephalitis virus (JEV) infection from other flavivirus especially West Nile virus (WNV) and Dengue virus (DV) infection was greatly hindered for the serological cross-reactive. Virus specific epitopes could benefit for developing JEV specific antibodies detection methods. To identify the JEV specific epitopes, we fully mapped and characterized the continuous B-cell epitope of the PrM/M protein of JEV. RESULTS: To map the epitopes on the PrM/M protein, we designed a set of 20 partially overlapping fragments spanning the whole PrM, fused them with GST, and expressed them in an expression vector. Linear epitope M14 ((105)VNKKEAWLDSTKATRY(120)) was detected by enzyme-linked immunosorbent assay (ELISA). By removing amino acid residues individually from the carboxy and amino terminal of peptide M14, we confirmed that the minimal unit of the linear epitope of PrM/M was M14-13 ((108)KEAWLDSTKAT(118)). This epitope was highly conserved across different JEV strains. Moreover, this epitope did not cross-react with WNV-positive and DENV-positive sera. CONCLUSION: Epitope M14-13 was a JEV specific lineal B-cell epitpe. The results may provide a useful basis for the development of epitope-based virus specific diagnostic clinical techniques.",2010 Sep 22,"['Hua, Rong-Hong', 'Chen, Na-Sha', 'Qin, Cheng-Feng', 'Deng, Yong-Qiang', 'Ge, Jin-Ying', 'Wang, Xi-Jun', 'Qiao, Zu-Jian', 'Chen, Wei-Ye', 'Wen, Zhi-Yuan', 'Liu, Wen-Xin', 'Hu, Sen', 'Bu, Zhi-Gao']",Virol J,,,True
4cc161090a796945e7bda63489feb4f268bfeb3a,PMC,Identification of NCAM that interacts with the PHE-CoV spike protein,http://dx.doi.org/10.1186/1743-422X-7-254,PMC2955716,20863409,CC BY,"BACKGROUND: The spike proteins of coronaviruses associate with cellular molecules to mediate infection of their target cells. The characterization of cellular proteins required for virus infection is essential for understanding viral life cycles and may provide cellular targets for antiviral therapies. RESULTS: We identified Neural Cell Adhesion Molecule (NCAM) as a novel interacting partner of the PHE-CoV S protein. A T7 phage display cDNA library from N2a cells was constructed, and the library was screened with the soluble PHE-CoV S glycoproteins. We used a coimmunoprecipitation assay to show that only the NCAM was a binding partner of spike protein. We found that a soluble form of anti-NCAM antibody blocked association of the PHE-CoV with N2a cells. Furthermore, double-stranded siRNA targeted against NCAM inhibited PHE-CoV infection. CONCLUSIONS: A novel interaction was identified between NCAM and spike protein and this association is critical during PHE-CoV infection.",2010 Sep 24,"['Gao, Wei', 'He, Wenqi', 'Zhao, Kui', 'Lu, Huijun', 'Ren, Wenzhi', 'Du, Chongtao', 'Chen, Keyan', 'Lan, Yungang', 'Song, Deguang', 'Gao, Feng']",Virol J,,,True
ccfba2653a0baee4d4a733902529dc5c96bc69d5,PMC,A Metagenomic Analysis of Pandemic Influenza A (2009 H1N1) Infection in Patients from North America,http://dx.doi.org/10.1371/journal.pone.0013381,PMC2956640,20976137,CC BY,"Although metagenomics has been previously employed for pathogen discovery, its cost and complexity have prevented its use as a practical front-line diagnostic for unknown infectious diseases. Here we demonstrate the utility of two metagenomics-based strategies, a pan-viral microarray (Virochip) and deep sequencing, for the identification and characterization of 2009 pandemic H1N1 influenza A virus. Using nasopharyngeal swabs collected during the earliest stages of the pandemic in Mexico, Canada, and the United States (n = 17), the Virochip was able to detect a novel virus most closely related to swine influenza viruses without a priori information. Deep sequencing yielded reads corresponding to 2009 H1N1 influenza in each sample (percentage of aligned sequences corresponding to 2009 H1N1 ranging from 0.0011% to 10.9%), with up to 97% coverage of the influenza genome in one sample. Detection of 2009 H1N1 by deep sequencing was possible even at titers near the limits of detection for specific RT-PCR, and the percentage of sequence reads was linearly correlated with virus titer. Deep sequencing also provided insights into the upper respiratory microbiota and host gene expression in response to 2009 H1N1 infection. An unbiased analysis combining sequence data from all 17 outbreak samples revealed that 90% of the 2009 H1N1 genome could be assembled de novo without the use of any reference sequence, including assembly of several near full-length genomic segments. These results indicate that a streamlined metagenomics detection strategy can potentially replace the multiple conventional diagnostic tests required to investigate an outbreak of a novel pathogen, and provide a blueprint for comprehensive diagnosis of unexplained acute illnesses or outbreaks in clinical and public health settings.",2010 Oct 18,"['Greninger, Alexander L.', 'Chen, Eunice C.', 'Sittler, Taylor', 'Scheinerman, Alex', 'Roubinian, Nareg', 'Yu, Guixia', 'Kim, Edward', 'Pillai, Dylan R.', 'Guyard, Cyril', 'Mazzulli, Tony', 'Isa, Pavel', 'Arias, Carlos F.', 'Hackett, John', 'Schochetman, Gerald', 'Miller, Steve', 'Tang, Patrick', 'Chiu, Charles Y.']",PLoS One,,,True
d4d0092e3e79f9d5ad3c48f23778317ad867d61c,PMC,Nodeomics: Pathogen Detection in Vertebrate Lymph Nodes Using Meta-Transcriptomics,http://dx.doi.org/10.1371/journal.pone.0013432,PMC2956653,20976145,CC0,"The ongoing emergence of human infections originating from wildlife highlights the need for better knowledge of the microbial community in wildlife species where traditional diagnostic approaches are limited. Here we evaluate the microbial biota in healthy mule deer (Odocoileus hemionus) by analyses of lymph node meta-transcriptomes. cDNA libraries from five individuals and two pools of samples were prepared from retropharyngeal lymph node RNA enriched for polyadenylated RNA and sequenced using Roche-454 Life Sciences technology. Protein-coding and 16S ribosomal RNA (rRNA) sequences were taxonomically profiled using protein and rRNA specific databases. Representatives of all bacterial phyla were detected in the seven libraries based on protein-coding transcripts indicating that viable microbiota were present in lymph nodes. Residents of skin and rumen, and those ubiquitous in mule deer habitat dominated classifiable bacterial species. Based on detection of both rRNA and protein-coding transcripts, we identified two new proteobacterial species; a Helicobacter closely related to Helicobacter cetorum in the Helicobacter pylori/Helicobacter acinonychis complex and an Acinetobacter related to Acinetobacter schindleri. Among viruses, a novel gamma retrovirus and other members of the Poxviridae and Retroviridae were identified. We additionally evaluated bacterial diversity by amplicon sequencing the hypervariable V6 region of 16S rRNA and demonstrate that overall taxonomic diversity is higher with the meta-transcriptomic approach. These data provide the most complete picture to date of the microbial diversity within a wildlife host. Our research advances the use of meta-transcriptomics to study microbiota in wildlife tissues, which will facilitate detection of novel organisms with pathogenic potential to human and animals.",2010 Oct 18,"['Wittekindt, Nicola E.', 'Padhi, Abinash', 'Schuster, Stephan C.', 'Qi, Ji', 'Zhao, Fangqing', 'Tomsho, Lynn P.', 'Kasson, Lindsay R.', 'Packard, Michael', 'Cross, Paul', 'Poss, Mary']",PLoS One,,,True
a2a873c09a0bc1b59d326245310e25a83031cd62,PMC,Advances in Diagnosis of Respiratory Virus Infections,http://dx.doi.org/10.1155/2010/126049,PMC2958490,20981303,CC BY,"The diagnosis of respiratory virus infections has evolved substantially in recent years, with the emergence of new pathogens and the development of novel detection methods. While recent advances have improved the sensitivity and turn-around time of diagnostic tests for respiratory viruses, they have also raised important issues such as cost, and the clinical significance of detecting multiple viruses in a single specimen by molecular methods. This article reviews recent advances in specimen collection and detection methods for diagnosis of respiratory virus infections, and discusses the performance characteristics and limitations of these methods.",2010 Oct 19,"['Loeffelholz, Michael', 'Chonmaitree, Tasnee']",Int J Microbiol,,,True
39772fc7033bdfcfd0a6fb689d7a5c8bff2d80e1,PMC,In Vitro and In Vivo Studies Identify Important Features of Dengue Virus pr-E Protein Interactions,http://dx.doi.org/10.1371/journal.ppat.1001157,PMC2958806,20975939,CC BY,"Flaviviruses bud into the endoplasmic reticulum and are transported through the secretory pathway, where the mildly acidic environment triggers particle rearrangement and allows furin processing of the prM protein to pr and M. The peripheral pr peptide remains bound to virus at low pH and inhibits virus-membrane interaction. Upon exocytosis, the release of pr at neutral pH completes virus maturation to an infectious particle. Together this evidence suggests that pr may shield the flavivirus fusion protein E from the low pH environment of the exocytic pathway. Here we developed an in vitro system to reconstitute the interaction of dengue virus (DENV) pr with soluble truncated E proteins. At low pH recombinant pr bound to both monomeric and dimeric forms of E and blocked their membrane insertion. Exogenous pr interacted with mature infectious DENV and specifically inhibited virus fusion and infection. Alanine substitution of E H244, a highly conserved histidine residue in the pr-E interface, blocked pr-E interaction and reduced release of DENV virus-like particles. Folding, membrane insertion and trimerization of the H244A mutant E protein were preserved, and particle release could be partially rescued by neutralization of the low pH of the secretory pathway. Thus, pr acts to silence flavivirus fusion activity during virus secretion, and this function can be separated from the chaperone activity of prM. The sequence conservation of key residues involved in the flavivirus pr-E interaction suggests that this protein-protein interface may be a useful target for broad-spectrum inhibitors.",2010 Oct 21,"['Zheng, Aihua', 'Umashankar, Mahadevaiah', 'Kielian, Margaret']",PLoS Pathog,,,True
96996147e2d12f5db12dd32d730fd694be627d6f,PMC,In Vitro and In Vivo Studies Identify Important Features of Dengue Virus pr-E Protein Interactions,http://dx.doi.org/10.1371/journal.ppat.1001157,PMC2958806,20975939,CC BY,"Flaviviruses bud into the endoplasmic reticulum and are transported through the secretory pathway, where the mildly acidic environment triggers particle rearrangement and allows furin processing of the prM protein to pr and M. The peripheral pr peptide remains bound to virus at low pH and inhibits virus-membrane interaction. Upon exocytosis, the release of pr at neutral pH completes virus maturation to an infectious particle. Together this evidence suggests that pr may shield the flavivirus fusion protein E from the low pH environment of the exocytic pathway. Here we developed an in vitro system to reconstitute the interaction of dengue virus (DENV) pr with soluble truncated E proteins. At low pH recombinant pr bound to both monomeric and dimeric forms of E and blocked their membrane insertion. Exogenous pr interacted with mature infectious DENV and specifically inhibited virus fusion and infection. Alanine substitution of E H244, a highly conserved histidine residue in the pr-E interface, blocked pr-E interaction and reduced release of DENV virus-like particles. Folding, membrane insertion and trimerization of the H244A mutant E protein were preserved, and particle release could be partially rescued by neutralization of the low pH of the secretory pathway. Thus, pr acts to silence flavivirus fusion activity during virus secretion, and this function can be separated from the chaperone activity of prM. The sequence conservation of key residues involved in the flavivirus pr-E interaction suggests that this protein-protein interface may be a useful target for broad-spectrum inhibitors.",2010 Oct 21,"['Zheng, Aihua', 'Umashankar, Mahadevaiah', 'Kielian, Margaret']",PLoS Pathog,,,False
0049ba8861864506e1e8559e7815f4de8b03dbed,PMC,GPI-anchored single chain Fv - an effective way to capture transiently-exposed neutralization epitopes on HIV-1 envelope spike,http://dx.doi.org/10.1186/1742-4690-7-79,PMC2959034,20923574,CC BY,"BACKGROUND: Identification of broad neutralization epitopes in HIV-1 envelope spikes is paramount for HIV-1 vaccine development. A few broad neutralization epitopes identified so far are present on the surface of native HIV-1 envelope spikes whose recognition by antibodies does not depend on conformational changes of the envelope spikes. However, HIV-1 envelope spikes also contain transiently-exposed neutralization epitopes, which are more difficult to identify. RESULTS: In this study, we constructed single chain Fvs (scFvs) derived from seven human monoclonal antibodies and genetically linked them with or without a glycosyl-phosphatidylinositol (GPI) attachment signal. We show that with a GPI attachment signal the scFvs are targeted to lipid rafts of plasma membranes. In addition, we demonstrate that four of the GPI-anchored scFvs, but not their secreted counterparts, neutralize HIV-1 with various degrees of breadth and potency. Among them, GPI-anchored scFv (X5) exhibits extremely potent and broad neutralization activity against multiple clades of HIV-1 strains tested. Moreover, we show that GPI-anchored scFv (4E10) also exhibited more potent neutralization activity than its secretory counterpart. Finally, we demonstrate that expression of GPI-anchored scFv (X5) in the lipid raft of plasma membrane of human CD4(+ )T cells confers long-term resistance to HIV-1 infection, HIV-1 envelope-mediated cell-cell fusion, and the infection of HIV-1 captured and transferred by human DCs. CONCLUSIONS: Thus GPI-anchored scFv could be used as a general and effective way to identify antibodies that react with transiently-exposed neutralization epitopes in envelope proteins of HIV-1 and other enveloped viruses. The GPI-anchored scFv (X5), because of its breadth and potency, should have a great potential to be developed into anti-viral agent for HIV-1 prevention and therapy.",2010 Oct 6,"['Wen, Michael', 'Arora, Reetakshi', 'Wang, Huiqiang', 'Liu, Lihong', 'Kimata, Jason T', 'Zhou, Paul']",Retrovirology,,,True
611159c87e69ac113f1652442897b3cf96878939,PMC,C-reactive protein serum levels as an early predictor of outcome in patients with pandemic H1N1 influenza A virus infection,http://dx.doi.org/10.1186/1471-2334-10-288,PMC2959060,20920320,CC BY,"BACKGROUND: Data for predicting which patients with pandemic influenza A (H1N1) infection are likely to run a complicated course are sparse. We retrospectively studied whether the admission serum C-reactive protein (CRP) levels can serve as a predictor of illness severity. METHODS: Included were all consecutive adult patients who presented to the emergency department (ED) between May-December, 2009 with a flu-like illness, a confirmed diagnosis of pandemic influenza A (H1N1) infection and a serum CRP level measured within 24 hours of presentation. Patients with a proven additional concurrent acute illness (e.g., bacteremia) were excluded. We used the ROC curve analysis, Kaplan-Meier curves and the Cox proportional hazard model to evaluate the predictive ability of CRP as a prognostic factor. RESULTS: Seventeen (9%) of the 191 enrolled patients were admitted to the intensive care unit (ICU), of whom eight (4%) required mechanical ventilation and three (2%) died. The median admission serum CRP levels were significantly higher among patients who required subsequent ICU care and mechanical ventilation than among patients who did not (123 mg/L and 112 mg/L vs. 40 mg/L, p < .001 and 43 mg/L, p = .017, respectively). A Cox proportional hazard model identified admission serum CRP levels and auscultatory findings over the lungs as independent prognostic factors for ICU admission. Admission serum CRP levels were the only independent prognostic factor for mechanical ventilation. Thirty days after presenting to the ED, none of the patients with admission serum CRP level <28 mg/L (lower tertile) required either ICU admission or mechanical ventilation. At the same time point, 19% of the patients with admission serum CRP level ≥70 mg/L (upper tertile) needed to be admitted to the ICU and 8% of the same upper tertile group required mechanical ventilation. The differences in the rates between the lower vs. upper tertile groups were significant (Log-Rank p < .001 for ICU and p < .024 for mechanical ventilation). CONCLUSIONS: In our study group, serum CRP levels obtained in the early ED admission stage from patients presenting with pandemic H1N1 influenza A infection were found to serve as a useful gauge for predicting disease course and assisting in patient management.",2010 Oct 4,"['Zimmerman, Ofer', 'Rogowski, Ori', 'Aviram, Galit', 'Mizrahi, Michal', 'Zeltser, David', 'Justo, Dan', 'Dahan, Esther', 'Arad, Roy', 'Touvia, Oholi', 'Tau, Luba', 'Tarabeia, Jalal', 'Berliner, Shlomo', 'Paran, Yael']",BMC Infect Dis,,,True
8a584984728d9dd104a0d3928686d4a2e02e2ebf,PMC,The dynamics of risk perceptions and precautionary behavior in response to 2009 (H1N1) pandemic influenza,http://dx.doi.org/10.1186/1471-2334-10-296,PMC2964717,20946662,CC BY,"BACKGROUND: The trajectory of an infectious disease outbreak is affected by the behavior of individuals, and the behavior is often related to individuals' risk perception. We assessed temporal changes and geographical differences in risk perceptions and precautionary behaviors in response to H1N1 influenza. METHODS: 1,290 US adults completed an online survey on risk perceptions, interests in pharmaceutical interventions (preventive intervention and curative intervention), and engagement in precautionary activities (information seeking activities and taking quarantine measures) in response to H1N1 influenza between April 28 and May 27 2009. Associations of risk perceptions and precautionary behaviors with respondents' sex, age, and household size were analyzed. Linear and quadratic time trends were assessed by regression analyses. Geographic differences in risk perception and precautionary behaviors were evaluated. Predictors of willingness to take pharmaceutical intervention were analyzed. RESULTS: Respondents from larger households reported stronger interest in taking medications and engaged in more precautionary activities, as would be normatively predicted. Perceived risk increased over time, whereas interest in pharmaceutical preventive interventions and the engagement in some precautionary activities decreased over time. Respondents who live in states with higher H1N1 incidence per population perceived a higher likelihood of influenza infection, but did not express greater interests in pharmaceutical interventions, nor did they engage in a higher degree of precautionary activities. Perceived likelihood of influenza infection, willingness to take medications and engagement in information seeking activities were higher for women than men. CONCLUSIONS: Perceived risk of infection and precautionary behavior can be dynamic in time, and differ by demographic characteristics and geographical locations. These patterns will likely influence the effectiveness of disease control measures.",2010 Oct 14,"['Ibuka, Yoko', 'Chapman, Gretchen B', 'Meyers, Lauren A', 'Li, Meng', 'Galvani, Alison P']",BMC Infect Dis,,,True
68a2d0b2dfdcee12dec8aaf910ccbffc49b83a85,PMC,The dynamics of risk perceptions and precautionary behavior in response to 2009 (H1N1) pandemic influenza,http://dx.doi.org/10.1186/1471-2334-10-296,PMC2964717,20946662,CC BY,"BACKGROUND: The trajectory of an infectious disease outbreak is affected by the behavior of individuals, and the behavior is often related to individuals' risk perception. We assessed temporal changes and geographical differences in risk perceptions and precautionary behaviors in response to H1N1 influenza. METHODS: 1,290 US adults completed an online survey on risk perceptions, interests in pharmaceutical interventions (preventive intervention and curative intervention), and engagement in precautionary activities (information seeking activities and taking quarantine measures) in response to H1N1 influenza between April 28 and May 27 2009. Associations of risk perceptions and precautionary behaviors with respondents' sex, age, and household size were analyzed. Linear and quadratic time trends were assessed by regression analyses. Geographic differences in risk perception and precautionary behaviors were evaluated. Predictors of willingness to take pharmaceutical intervention were analyzed. RESULTS: Respondents from larger households reported stronger interest in taking medications and engaged in more precautionary activities, as would be normatively predicted. Perceived risk increased over time, whereas interest in pharmaceutical preventive interventions and the engagement in some precautionary activities decreased over time. Respondents who live in states with higher H1N1 incidence per population perceived a higher likelihood of influenza infection, but did not express greater interests in pharmaceutical interventions, nor did they engage in a higher degree of precautionary activities. Perceived likelihood of influenza infection, willingness to take medications and engagement in information seeking activities were higher for women than men. CONCLUSIONS: Perceived risk of infection and precautionary behavior can be dynamic in time, and differ by demographic characteristics and geographical locations. These patterns will likely influence the effectiveness of disease control measures.",2010 Oct 14,"['Ibuka, Yoko', 'Chapman, Gretchen B', 'Meyers, Lauren A', 'Li, Meng', 'Galvani, Alison P']",BMC Infect Dis,,,False
d0a71fb07c6dfa2d5d78fdd4be9b7cb8f4be5205,PMC,The dynamics of risk perceptions and precautionary behavior in response to 2009 (H1N1) pandemic influenza,http://dx.doi.org/10.1186/1471-2334-10-296,PMC2964717,20946662,CC BY,"BACKGROUND: The trajectory of an infectious disease outbreak is affected by the behavior of individuals, and the behavior is often related to individuals' risk perception. We assessed temporal changes and geographical differences in risk perceptions and precautionary behaviors in response to H1N1 influenza. METHODS: 1,290 US adults completed an online survey on risk perceptions, interests in pharmaceutical interventions (preventive intervention and curative intervention), and engagement in precautionary activities (information seeking activities and taking quarantine measures) in response to H1N1 influenza between April 28 and May 27 2009. Associations of risk perceptions and precautionary behaviors with respondents' sex, age, and household size were analyzed. Linear and quadratic time trends were assessed by regression analyses. Geographic differences in risk perception and precautionary behaviors were evaluated. Predictors of willingness to take pharmaceutical intervention were analyzed. RESULTS: Respondents from larger households reported stronger interest in taking medications and engaged in more precautionary activities, as would be normatively predicted. Perceived risk increased over time, whereas interest in pharmaceutical preventive interventions and the engagement in some precautionary activities decreased over time. Respondents who live in states with higher H1N1 incidence per population perceived a higher likelihood of influenza infection, but did not express greater interests in pharmaceutical interventions, nor did they engage in a higher degree of precautionary activities. Perceived likelihood of influenza infection, willingness to take medications and engagement in information seeking activities were higher for women than men. CONCLUSIONS: Perceived risk of infection and precautionary behavior can be dynamic in time, and differ by demographic characteristics and geographical locations. These patterns will likely influence the effectiveness of disease control measures.",2010 Oct 14,"['Ibuka, Yoko', 'Chapman, Gretchen B', 'Meyers, Lauren A', 'Li, Meng', 'Galvani, Alison P']",BMC Infect Dis,,,False
68a4cb26f4d7448117bfcb2d2794211c04605765,PMC,The dynamics of risk perceptions and precautionary behavior in response to 2009 (H1N1) pandemic influenza,http://dx.doi.org/10.1186/1471-2334-10-296,PMC2964717,20946662,CC BY,"BACKGROUND: The trajectory of an infectious disease outbreak is affected by the behavior of individuals, and the behavior is often related to individuals' risk perception. We assessed temporal changes and geographical differences in risk perceptions and precautionary behaviors in response to H1N1 influenza. METHODS: 1,290 US adults completed an online survey on risk perceptions, interests in pharmaceutical interventions (preventive intervention and curative intervention), and engagement in precautionary activities (information seeking activities and taking quarantine measures) in response to H1N1 influenza between April 28 and May 27 2009. Associations of risk perceptions and precautionary behaviors with respondents' sex, age, and household size were analyzed. Linear and quadratic time trends were assessed by regression analyses. Geographic differences in risk perception and precautionary behaviors were evaluated. Predictors of willingness to take pharmaceutical intervention were analyzed. RESULTS: Respondents from larger households reported stronger interest in taking medications and engaged in more precautionary activities, as would be normatively predicted. Perceived risk increased over time, whereas interest in pharmaceutical preventive interventions and the engagement in some precautionary activities decreased over time. Respondents who live in states with higher H1N1 incidence per population perceived a higher likelihood of influenza infection, but did not express greater interests in pharmaceutical interventions, nor did they engage in a higher degree of precautionary activities. Perceived likelihood of influenza infection, willingness to take medications and engagement in information seeking activities were higher for women than men. CONCLUSIONS: Perceived risk of infection and precautionary behavior can be dynamic in time, and differ by demographic characteristics and geographical locations. These patterns will likely influence the effectiveness of disease control measures.",2010 Oct 14,"['Ibuka, Yoko', 'Chapman, Gretchen B', 'Meyers, Lauren A', 'Li, Meng', 'Galvani, Alison P']",BMC Infect Dis,,,True
2c6d1fc20495ba6b8b43ffe06cc0d9bb80244d96,PMC,Inhibitory effect of small interfering RNA on dengue virus replication in mosquito cells,http://dx.doi.org/10.1186/1743-422X-7-270,PMC2965154,20946645,CC BY,"BACKGROUND: Dengue viruses (DENs) are the wildest transmitted mosquito-borne pathogens throughout tropical and sub-tropical regions worldwide. Infection with DENs can cause severe flu-like illness and potentially fatal hemorrhagic fever. Although RNA interference triggered by long-length dsRNA was considered a potent antiviral pathway in the mosquito, only limited studies of the value of small interfering RNA (siRNA) have been conducted. RESULTS: A 21 nt siRNA targeting the membrane glycoprotein precursor gene of DEN-1 was synthesized and transfected into mosquito C6/36 cells followed by challenge with DEN. The stability of the siRNA in cells was monitored by flow cytometry. The antiviral effect of siRNA was evaluated by measurement of cell survival rate using the MTT method and viral RNA was quantitated with real-time RT-PCR. The presence of cells containing siRNA at 0.25, 1, 3, 5, 7 days after transfection were 66.0%, 52.1%, 32.0%, 13.5% and 8.9%, respectively. After 7 days incubation with DEN, there was reduced cytopathic effect, increased cell survival rate (76.9 ± 4.5% vs 23.6 ± 14.6%) and reduced viral RNA copies (Ct value 19.91 ± 0.63 vs 14.56 ± 0.39) detected in transfected C6/36 cells. CONCLUSIONS: Our data showed that synthetic siRNA against the DEN-1 membrane glycoprotein precursor gene effectively inhibited DEN-1 viral RNA replication and increased C6/36 cell survival rate. siRNA may offer a potential new strategy for prevention and treatment of DEN infection.",2010 Oct 14,"['Wu, Xinwei', 'Hong, Hua', 'Yue, Jinya', 'Wu, Yejian', 'Li, Xiangzhong', 'Jiang, Liyun', 'Li, Lei', 'Li, Qiaoyan', 'Gao, Guoquan', 'Yang, Xia']",Virol J,,,True
dbaaa5a246123fee5013bba144f693f96e624988,PMC,"Fidelity Variants of RNA Dependent RNA Polymerases Uncover an Indirect, Mutagenic Activity of Amiloride Compounds",http://dx.doi.org/10.1371/journal.ppat.1001163,PMC2965762,21060812,CC BY,"In a screen for RNA mutagen resistance, we isolated a high fidelity RNA dependent RNA polymerase (RdRp) variant of Coxsackie virus B3 (CVB3). Curiously, this variant A372V is also resistant to amiloride. We hypothesize that amiloride has a previously undescribed mutagenic activity. Indeed, amiloride compounds increase the mutation frequencies of CVB3 and poliovirus and high fidelity variants of both viruses are more resistant to this effect. We hypothesize that this mutagenic activity is mediated through alterations in intracellular ions such as Mg(2+) and Mn(2+), which in turn increase virus mutation frequency by affecting RdRp fidelity. Furthermore, we show that another amiloride-resistant RdRp variant, S299T, is completely resistant to this mutagenic activity and unaffected by changes in ion concentrations. We show that RdRp variants resist the mutagenic activity of amiloride via two different mechanisms: 1) increased fidelity that generates virus populations presenting lower basal mutation frequencies or 2) resisting changes in divalent cation concentrations that affect polymerase fidelity. Our results uncover a new antiviral approach based on mutagenesis.",2010 Oct 28,"['Levi, Laura I.', 'Gnädig, Nina F.', 'Beaucourt, Stéphanie', 'McPherson, Malia J.', 'Baron, Bruno', 'Arnold, Jamie J.', 'Vignuzzi, Marco']",PLoS Pathog,,,True
951ba94a08a28e0cc4264dcfd46270625d3efab1,PMC,"Fidelity Variants of RNA Dependent RNA Polymerases Uncover an Indirect, Mutagenic Activity of Amiloride Compounds",http://dx.doi.org/10.1371/journal.ppat.1001163,PMC2965762,21060812,CC BY,"In a screen for RNA mutagen resistance, we isolated a high fidelity RNA dependent RNA polymerase (RdRp) variant of Coxsackie virus B3 (CVB3). Curiously, this variant A372V is also resistant to amiloride. We hypothesize that amiloride has a previously undescribed mutagenic activity. Indeed, amiloride compounds increase the mutation frequencies of CVB3 and poliovirus and high fidelity variants of both viruses are more resistant to this effect. We hypothesize that this mutagenic activity is mediated through alterations in intracellular ions such as Mg(2+) and Mn(2+), which in turn increase virus mutation frequency by affecting RdRp fidelity. Furthermore, we show that another amiloride-resistant RdRp variant, S299T, is completely resistant to this mutagenic activity and unaffected by changes in ion concentrations. We show that RdRp variants resist the mutagenic activity of amiloride via two different mechanisms: 1) increased fidelity that generates virus populations presenting lower basal mutation frequencies or 2) resisting changes in divalent cation concentrations that affect polymerase fidelity. Our results uncover a new antiviral approach based on mutagenesis.",2010 Oct 28,"['Levi, Laura I.', 'Gnädig, Nina F.', 'Beaucourt, Stéphanie', 'McPherson, Malia J.', 'Baron, Bruno', 'Arnold, Jamie J.', 'Vignuzzi, Marco']",PLoS Pathog,,,False
e8392d9561be82ded77c6e5d75f321d752776424,PMC,Prevalence and Phylogeny of Coronaviruses in Wild Birds from the Bering Strait Area (Beringia),http://dx.doi.org/10.1371/journal.pone.0013640,PMC2966397,21060827,CC BY,"Coronaviruses (CoVs) can cause mild to severe disease in humans and animals, their host range and environmental spread seem to have been largely underestimated, and they are currently being investigated for their potential medical relevance. Infectious bronchitis virus (IBV) belongs to gamma-coronaviruses and causes a costly respiratory viral disease in chickens. The role of wild birds in the epidemiology of IBV is poorly understood. In the present study, we examined 1,002 cloacal and faecal samples collected from 26 wild bird species in the Beringia area for the presence of CoVs, and then we performed statistical and phylogenetic analyses. We detected diverse CoVs by RT-PCR in wild birds in the Beringia area. Sequence analysis showed that the detected viruses are gamma-coronaviruses related to IBV. These findings suggest that wild birds are able to carry gamma-coronaviruses asymptomatically. We concluded that CoVs are widespread among wild birds in Beringia, and their geographic spread and frequency is higher than previously realised. Thus, Avian CoV can be efficiently disseminated over large distances and could be a genetic reservoir for future emerging pathogenic CoVs. Considering the great animal health and economic impact of IBV as well as the recent emergence of novel coronaviruses such as SARS-coronavirus, it is important to investigate the role of wildlife reservoirs in CoV infection biology and epidemiology.",2010 Oct 29,"['Muradrasoli, Shaman', 'Bálint, Ádám', 'Wahlgren, John', 'Waldenström, Jonas', 'Belák, Sándor', 'Blomberg, Jonas', 'Olsen, Björn']",PLoS One,,,True
1e7bcacaa32d4c0f5ed60e5e56897404d3896d81,PMC,Real-Time Fluorescence Loop Mediated Isothermal Amplification for the Diagnosis of Malaria,http://dx.doi.org/10.1371/journal.pone.0013733,PMC2966401,21060829,CC0,"BACKGROUND: Molecular diagnostic methods can complement existing tools to improve the diagnosis of malaria. However, they require good laboratory infrastructure thereby restricting their use to reference laboratories and research studies. Therefore, adopting molecular tools for routine use in malaria endemic countries will require simpler molecular platforms. The recently developed loop-mediated isothermal amplification (LAMP) method is relatively simple and can be improved for better use in endemic countries. In this study, we attempted to improve this method for malaria diagnosis by using a simple and portable device capable of performing both the amplification and detection (by fluorescence) of LAMP in one platform. We refer to this as the RealAmp method. METHODOLOGY AND SIGNIFICANT FINDINGS: Published genus-specific primers were used to test the utility of this method. DNA derived from different species of malaria parasites was used for the initial characterization. Clinical samples of P. falciparum were used to determine the sensitivity and specificity of this system compared to microscopy and a nested PCR method. Additionally, directly boiled parasite preparations were compared with a conventional DNA isolation method. The RealAmp method was found to be simple and allowed real-time detection of DNA amplification. The time to amplification varied but was generally less than 60 minutes. All human-infecting Plasmodium species were detected. The sensitivity and specificity of RealAmp in detecting P. falciparum was 96.7% and 91.7% respectively, compared to microscopy and 98.9% and 100% respectively, compared to a standard nested PCR method. In addition, this method consistently detected P. falciparum from directly boiled blood samples. CONCLUSION: This RealAmp method has great potential as a field usable molecular tool for diagnosis of malaria. This tool can provide an alternative to conventional PCR based diagnostic methods for field use in clinical and operational programs.",2010 Oct 29,"['Lucchi, Naomi W.', 'Demas, Allison', 'Narayanan, Jothikumar', 'Sumari, Deborah', 'Kabanywanyi, Abdunoor', 'Kachur, S. Patrick', 'Barnwell, John W.', 'Udhayakumar, Venkatachalam']",PLoS One,,,True
073d9b195e4d3e325a8ec7cd30b9ec23bb0a00a7,PMC,Efficacy of Oseltamivir-Zanamivir Combination Compared to Each Monotherapy for Seasonal Influenza: A Randomized Placebo-Controlled Trial,http://dx.doi.org/10.1371/journal.pmed.1000362,PMC2970549,21072246,CC BY,"BACKGROUND: Neuraminidase inhibitors are thought to be efficacious in reducing the time to alleviation of symptoms in outpatients with seasonal influenza. The objective of this study was to compare the short-term virological efficacy of oseltamivir-zanamivir combination versus each monotherapy plus placebo. METHODS AND FINDINGS: We conducted a randomized placebo-controlled trial with 145 general practitioners throughout France during the 2008–2009 seasonal influenza epidemic. Patients, general practitioners, and outcome assessors were all blinded to treatment assignment. Adult outpatients presenting influenza-like illness for less than 36 hours and a positive influenza A rapid test diagnosis were randomized to oseltamivir 75 mg orally twice daily plus zanamivir 10 mg by inhalation twice daily (OZ), oseltamivir plus inhaled placebo (O), or zanamivir plus oral placebo (Z). Treatment efficacy was assessed virologically according to the proportion of patients with nasal influenza reverse transcription (RT)-PCR below 200 copies genome equivalent (cgeq)/µl at day 2 (primary outcome), and clinically to the time to alleviation of symptoms until day 14. Overall 541 patients (of the 900 planned) were included (OZ, n = 192; O, n = 176; Z, n = 173), 49% male, mean age 39 years. In the intention-to-treat analysis conducted in the 447 patients with RT-PCR-confirmed influenza A, 46%, 59%, and 34% in OZ (n = 157), O (n = 141), and Z (n = 149) arms had RT-PCR<200 cgeq/µl (−13.0%, 95% confidence interval [CI] −23.1 to −2.9, p = 0.025; +12.3%, 95% CI 2.39–22.2, p = 0.028 for OZ/O and OZ/Z comparisons). Mean day 0 to day 2 viral load decrease was 2.14, 2.49, and 1.68 log(10) cgeq/µl (p = 0.060, p = 0.016 for OZ/O and OZ/Z). Median time to alleviation of symptoms was 4.0, 3.0, and 4.0 days (+1.0, 95% CI 0.0–4.0, p = 0.018; +0.0, 95% CI −3.0 to 3.0, p = 0.960 for OZ/O and OZ/Z). Four severe adverse events were observed. Nausea and/or vomiting tended to be more frequent in the combination arm (OZ, n = 13; O, n = 4; and Z, n = 5 patients, respectively). CONCLUSIONS: In adults with seasonal influenza A mainly H3N2 virus infection, the oseltamivir-zanamivir combination appeared less effective than oseltamivir monotherapy, and not significantly more effective than zanamivir monotherapy. Despite the theoretical potential for the reduction of the emergence of antiviral resistance, the lower effectiveness of this combination calls for caution in its use in clinical practice. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00799760 Please see later in the article for the Editors' Summary",2010 Nov 2,"['Duval, Xavier', 'van der Werf, Sylvie', 'Blanchon, Thierry', 'Mosnier, Anne', 'Bouscambert-Duchamp, Maude', 'Tibi, Annick', 'Enouf, Vincent', 'Charlois-Ou, Cécile', 'Vincent, Corine', 'Andreoletti, Laurent', 'Tubach, Florence', 'Lina, Bruno', 'Mentré, France', 'Leport, Catherine', None]",PLoS Med,,,True
21f0073aa9c5c592c81fd9db4e11d61a35865cf7,PMC,Efficacy of Oseltamivir-Zanamivir Combination Compared to Each Monotherapy for Seasonal Influenza: A Randomized Placebo-Controlled Trial,http://dx.doi.org/10.1371/journal.pmed.1000362,PMC2970549,21072246,CC BY,"BACKGROUND: Neuraminidase inhibitors are thought to be efficacious in reducing the time to alleviation of symptoms in outpatients with seasonal influenza. The objective of this study was to compare the short-term virological efficacy of oseltamivir-zanamivir combination versus each monotherapy plus placebo. METHODS AND FINDINGS: We conducted a randomized placebo-controlled trial with 145 general practitioners throughout France during the 2008–2009 seasonal influenza epidemic. Patients, general practitioners, and outcome assessors were all blinded to treatment assignment. Adult outpatients presenting influenza-like illness for less than 36 hours and a positive influenza A rapid test diagnosis were randomized to oseltamivir 75 mg orally twice daily plus zanamivir 10 mg by inhalation twice daily (OZ), oseltamivir plus inhaled placebo (O), or zanamivir plus oral placebo (Z). Treatment efficacy was assessed virologically according to the proportion of patients with nasal influenza reverse transcription (RT)-PCR below 200 copies genome equivalent (cgeq)/µl at day 2 (primary outcome), and clinically to the time to alleviation of symptoms until day 14. Overall 541 patients (of the 900 planned) were included (OZ, n = 192; O, n = 176; Z, n = 173), 49% male, mean age 39 years. In the intention-to-treat analysis conducted in the 447 patients with RT-PCR-confirmed influenza A, 46%, 59%, and 34% in OZ (n = 157), O (n = 141), and Z (n = 149) arms had RT-PCR<200 cgeq/µl (−13.0%, 95% confidence interval [CI] −23.1 to −2.9, p = 0.025; +12.3%, 95% CI 2.39–22.2, p = 0.028 for OZ/O and OZ/Z comparisons). Mean day 0 to day 2 viral load decrease was 2.14, 2.49, and 1.68 log(10) cgeq/µl (p = 0.060, p = 0.016 for OZ/O and OZ/Z). Median time to alleviation of symptoms was 4.0, 3.0, and 4.0 days (+1.0, 95% CI 0.0–4.0, p = 0.018; +0.0, 95% CI −3.0 to 3.0, p = 0.960 for OZ/O and OZ/Z). Four severe adverse events were observed. Nausea and/or vomiting tended to be more frequent in the combination arm (OZ, n = 13; O, n = 4; and Z, n = 5 patients, respectively). CONCLUSIONS: In adults with seasonal influenza A mainly H3N2 virus infection, the oseltamivir-zanamivir combination appeared less effective than oseltamivir monotherapy, and not significantly more effective than zanamivir monotherapy. Despite the theoretical potential for the reduction of the emergence of antiviral resistance, the lower effectiveness of this combination calls for caution in its use in clinical practice. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00799760 Please see later in the article for the Editors' Summary",2010 Nov 2,"['Duval, Xavier', 'van der Werf, Sylvie', 'Blanchon, Thierry', 'Mosnier, Anne', 'Bouscambert-Duchamp, Maude', 'Tibi, Annick', 'Enouf, Vincent', 'Charlois-Ou, Cécile', 'Vincent, Corine', 'Andreoletti, Laurent', 'Tubach, Florence', 'Lina, Bruno', 'Mentré, France', 'Leport, Catherine', None]",PLoS Med,,,True
0add910e9efb81f7b906101a7790b812074dc8b3,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,True
685e9506934c5e4c21c16a02f8c1e11aeeac1bac,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
a7069f86aa3a4d5231c386f08dd28dc3a97b0e0a,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,True
44d0aa144ed562f3811296688dc32d5add62678b,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
2ceafef80beea68922bc46a20a1299a56e5bddeb,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
84c2fe9c415572856b9c3cfc9722fcfc89127b68,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
66a0595238818c1e4e48ba0f89f15ea08f9fd1a6,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
eea89bf2af7757da44d13727fe9d10778352ea6c,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
b2ec5f13ee8c9a0cf5c691dc80e47788560c4e0c,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
131fbbb0a24a397047bb66fce5410c8fb1a5b300,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
362a6ff84fb689abbd3ca367fb077715c3dab5e1,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
930ed6116159ae51ee3c93acdeddb236a52d2852,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
536fb2baa603b0a3beca95431fd27e15fb630674,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
59f76abd6a9b78975746a86efb68d4ef40feac8e,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
206d1b4ad96a589f904f8dc7383bfe7cf68f9a59,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,False
4c572b27658746d48b85b25fa8aa9c6d94a47bcf,PMC,Human-Specific Evolution and Adaptation Led to Major Qualitative Differences in the Variable Receptors of Human and Chimpanzee Natural Killer Cells,http://dx.doi.org/10.1371/journal.pgen.1001192,PMC2973822,21079681,CC BY,"Natural killer (NK) cells serve essential functions in immunity and reproduction. Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. Because KIR have considerable species-specificity and are lacking from common animal models, we performed extensive comparison of the systems of KIR and MHC class I interaction in humans and chimpanzees. Although of similar complexity, they differ in genomic organization, gene content, and diversification mechanisms, mainly because of human-specific specialization in the KIR that recognizes the C1 and C2 epitopes of MHC-B and -C. Humans uniquely focused KIR recognition on MHC-C, while losing C1-bearing MHC-B. Reversing this trend, C1-bearing HLA-B46 was recently driven to unprecedented high frequency in Southeast Asia. Chimpanzees have a variety of ancient, avid, and predominantly inhibitory receptors, whereas human receptors are fewer, recently evolved, and combine avid inhibitory receptors with attenuated activating receptors. These differences accompany human-specific evolution of the A and B haplotypes that are under balancing selection and differentially function in defense and reproduction. Our study shows how the qualitative differences that distinguish the human and chimpanzee systems of KIR and MHC class I predominantly derive from adaptations on the human line in response to selective pressures placed on human NK cells by the competing needs of defense and reproduction.",2010 Nov 4,"['Abi-Rached, Laurent', 'Moesta, Achim K.', 'Rajalingam, Raja', 'Guethlein, Lisbeth A.', 'Parham, Peter']",PLoS Genet,,,True
80ae2988547a9163342117a914b53b6a63487901,PMC,Translation Elongation Factor 1A Facilitates the Assembly of the Tombusvirus Replicase and Stimulates Minus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1001175,PMC2973826,21079685,CC BY,"Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes. Previous studies showed that eukaryotic translation elongation factor (eEF1A) is one of the resident host proteins in the highly purified tombusvirus replicase complex. Using a random library of eEF1A mutants, we identified one mutant that decreased and three mutants that increased Tomato bushy stunt virus (TBSV) replication in a yeast model host. Additional in vitro assays with whole cell extracts prepared from yeast strains expressing the eEF1A mutants demonstrated several functions for eEF1A in TBSV replication: facilitating the recruitment of the viral RNA template into the replicase complex; the assembly of the viral replicase complex; and enhancement of the minus-strand synthesis by promoting the initiation step. These roles for eEF1A are separate from its canonical role in host and viral protein translation, emphasizing critical functions for this abundant cellular protein during TBSV replication.",2010 Nov 4,"['Li, Zhenghe', 'Pogany, Judit', 'Tupman, Steven', 'Esposito, Anthony M.', 'Kinzy, Terri Goss', 'Nagy, Peter D.']",PLoS Pathog,,,True
4fb69ac9627ce50a185d8476c9a0cdcd047a9c72,PMC,Translation Elongation Factor 1A Facilitates the Assembly of the Tombusvirus Replicase and Stimulates Minus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1001175,PMC2973826,21079685,CC BY,"Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes. Previous studies showed that eukaryotic translation elongation factor (eEF1A) is one of the resident host proteins in the highly purified tombusvirus replicase complex. Using a random library of eEF1A mutants, we identified one mutant that decreased and three mutants that increased Tomato bushy stunt virus (TBSV) replication in a yeast model host. Additional in vitro assays with whole cell extracts prepared from yeast strains expressing the eEF1A mutants demonstrated several functions for eEF1A in TBSV replication: facilitating the recruitment of the viral RNA template into the replicase complex; the assembly of the viral replicase complex; and enhancement of the minus-strand synthesis by promoting the initiation step. These roles for eEF1A are separate from its canonical role in host and viral protein translation, emphasizing critical functions for this abundant cellular protein during TBSV replication.",2010 Nov 4,"['Li, Zhenghe', 'Pogany, Judit', 'Tupman, Steven', 'Esposito, Anthony M.', 'Kinzy, Terri Goss', 'Nagy, Peter D.']",PLoS Pathog,,,False
7e27930203695841117f05b4e80661b8e317c1b6,PMC,Translation Elongation Factor 1A Facilitates the Assembly of the Tombusvirus Replicase and Stimulates Minus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1001175,PMC2973826,21079685,CC BY,"Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes. Previous studies showed that eukaryotic translation elongation factor (eEF1A) is one of the resident host proteins in the highly purified tombusvirus replicase complex. Using a random library of eEF1A mutants, we identified one mutant that decreased and three mutants that increased Tomato bushy stunt virus (TBSV) replication in a yeast model host. Additional in vitro assays with whole cell extracts prepared from yeast strains expressing the eEF1A mutants demonstrated several functions for eEF1A in TBSV replication: facilitating the recruitment of the viral RNA template into the replicase complex; the assembly of the viral replicase complex; and enhancement of the minus-strand synthesis by promoting the initiation step. These roles for eEF1A are separate from its canonical role in host and viral protein translation, emphasizing critical functions for this abundant cellular protein during TBSV replication.",2010 Nov 4,"['Li, Zhenghe', 'Pogany, Judit', 'Tupman, Steven', 'Esposito, Anthony M.', 'Kinzy, Terri Goss', 'Nagy, Peter D.']",PLoS Pathog,,,False
a0b861ad1d27b6dd11fe48aa245996a8d9bd01ec,PMC,Translation Elongation Factor 1A Facilitates the Assembly of the Tombusvirus Replicase and Stimulates Minus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1001175,PMC2973826,21079685,CC BY,"Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes. Previous studies showed that eukaryotic translation elongation factor (eEF1A) is one of the resident host proteins in the highly purified tombusvirus replicase complex. Using a random library of eEF1A mutants, we identified one mutant that decreased and three mutants that increased Tomato bushy stunt virus (TBSV) replication in a yeast model host. Additional in vitro assays with whole cell extracts prepared from yeast strains expressing the eEF1A mutants demonstrated several functions for eEF1A in TBSV replication: facilitating the recruitment of the viral RNA template into the replicase complex; the assembly of the viral replicase complex; and enhancement of the minus-strand synthesis by promoting the initiation step. These roles for eEF1A are separate from its canonical role in host and viral protein translation, emphasizing critical functions for this abundant cellular protein during TBSV replication.",2010 Nov 4,"['Li, Zhenghe', 'Pogany, Judit', 'Tupman, Steven', 'Esposito, Anthony M.', 'Kinzy, Terri Goss', 'Nagy, Peter D.']",PLoS Pathog,,,False
c75583662971c89996bdfa312d5c80f43c9950b2,PMC,Translation Elongation Factor 1A Facilitates the Assembly of the Tombusvirus Replicase and Stimulates Minus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1001175,PMC2973826,21079685,CC BY,"Replication of plus-strand RNA viruses depends on host factors that are recruited into viral replicase complexes. Previous studies showed that eukaryotic translation elongation factor (eEF1A) is one of the resident host proteins in the highly purified tombusvirus replicase complex. Using a random library of eEF1A mutants, we identified one mutant that decreased and three mutants that increased Tomato bushy stunt virus (TBSV) replication in a yeast model host. Additional in vitro assays with whole cell extracts prepared from yeast strains expressing the eEF1A mutants demonstrated several functions for eEF1A in TBSV replication: facilitating the recruitment of the viral RNA template into the replicase complex; the assembly of the viral replicase complex; and enhancement of the minus-strand synthesis by promoting the initiation step. These roles for eEF1A are separate from its canonical role in host and viral protein translation, emphasizing critical functions for this abundant cellular protein during TBSV replication.",2010 Nov 4,"['Li, Zhenghe', 'Pogany, Judit', 'Tupman, Steven', 'Esposito, Anthony M.', 'Kinzy, Terri Goss', 'Nagy, Peter D.']",PLoS Pathog,,,False
8a0a29d6e80385dfdfd8ea1a301cc15e430bb11e,PMC,Zn(2+) Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture,http://dx.doi.org/10.1371/journal.ppat.1001176,PMC2973827,21079686,CC BY,"Increasing the intracellular Zn(2+) concentration with zinc-ionophores like pyrithione (PT) can efficiently impair the replication of a variety of RNA viruses, including poliovirus and influenza virus. For some viruses this effect has been attributed to interference with viral polyprotein processing. In this study we demonstrate that the combination of Zn(2+) and PT at low concentrations (2 µM Zn(2+) and 2 µM PT) inhibits the replication of SARS-coronavirus (SARS-CoV) and equine arteritis virus (EAV) in cell culture. The RNA synthesis of these two distantly related nidoviruses is catalyzed by an RNA-dependent RNA polymerase (RdRp), which is the core enzyme of their multiprotein replication and transcription complex (RTC). Using an activity assay for RTCs isolated from cells infected with SARS-CoV or EAV—thus eliminating the need for PT to transport Zn(2+) across the plasma membrane—we show that Zn(2+) efficiently inhibits the RNA-synthesizing activity of the RTCs of both viruses. Enzymatic studies using recombinant RdRps (SARS-CoV nsp12 and EAV nsp9) purified from E. coli subsequently revealed that Zn(2+) directly inhibited the in vitro activity of both nidovirus polymerases. More specifically, Zn(2+) was found to block the initiation step of EAV RNA synthesis, whereas in the case of the SARS-CoV RdRp elongation was inhibited and template binding reduced. By chelating Zn(2+) with MgEDTA, the inhibitory effect of the divalent cation could be reversed, which provides a novel experimental tool for in vitro studies of the molecular details of nidovirus replication and transcription.",2010 Nov 4,"['te Velthuis, Aartjan J. W.', 'van den Worm, Sjoerd H. E.', 'Sims, Amy C.', 'Baric, Ralph S.', 'Snijder, Eric J.', 'van Hemert, Martijn J.']",PLoS Pathog,,,True
6daca390ad9b7e330f843410f2218f0b27915cd0,PMC,The calculation of information and organismal complexity,http://dx.doi.org/10.1186/1745-6150-5-59,PMC2973933,20937149,CC BY,"BACKGROUND: It is difficult to measure precisely the phenotypic complexity of living organisms. Here we propose a method to calculate the minimal amount of genomic information needed to construct organism (effective information) as a measure of organismal complexity, by using permutation and combination formulas and Shannon's information concept. RESULTS: The results demonstrate that the calculated information correlates quite well with the intuitive organismal phenotypic complexity defined by traditional taxonomy and evolutionary theory. From viruses to human beings, the effective information gradually increases, from thousands of bits to hundreds of millions of bits. The simpler the organism is, the less the information; the more complex the organism, the more the information. About 13% of human genome is estimated as effective information or functional sequence. CONCLUSIONS: The effective information can be used as a quantitative measure of phenotypic complexity of living organisms and also as an estimate of functional fraction of genome. REVIEWERS: This article was reviewed by Dr. Lavanya Kannan (nominated by Dr. Arcady Mushegian), Dr. Chao Chen, and Dr. ED Rietman (nominated by Dr. Marc Vidal).",2010 Oct 12,"['Jiang, Yun', 'Xu, Cunshuan']",Biol Direct,,,True
e7a8dfcde06b70cb86b30074d9008635252d6301,PMC,Computer aided selection of candidate vaccine antigens,http://dx.doi.org/10.1186/1745-7580-6-S2-S1,PMC2981880,21067543,CC BY,"Immunoinformatics is an emergent branch of informatics science that long ago pullulated from the tree of knowledge that is bioinformatics. It is a discipline which applies informatic techniques to problems of the immune system. To a great extent, immunoinformatics is typified by epitope prediction methods. It has found disappointingly limited use in the design and discovery of new vaccines, which is an area where proper computational support is generally lacking. Most extant vaccines are not based around isolated epitopes but rather correspond to chemically-treated or attenuated whole pathogens or correspond to individual proteins extract from whole pathogens or correspond to complex carbohydrate. In this chapter we attempt to review what progress there has been in an as-yet-underexplored area of immunoinformatics: the computational discovery of whole protein antigens. The effective development of antigen prediction methods would significantly reduce the laboratory resource required to identify pathogenic proteins as candidate subunit vaccines. We begin our review by placing antigen prediction firmly into context, exploring the role of reverse vaccinology in the design and discovery of vaccines. We also highlight several competing yet ultimately complementary methodological approaches: sub-cellular location prediction, identifying antigens using sequence similarity, and the use of sophisticated statistical approaches for predicting the probability of antigen characteristics. We end by exploring how a systems immunomics approach to the prediction of immunogenicity would prove helpful in the prediction of antigens.",2010 Nov 3,"['Flower, Darren R', 'Macdonald, Isabel K', 'Ramakrishnan, Kamna', 'Davies, Matthew N', 'Doytchinova, Irini A']",Immunome Res,,,True
816fc25c7f0997c17db295c0a77b18b1a2375338,PMC,Models of RNA virus evolution and their roles in vaccine design,http://dx.doi.org/10.1186/1745-7580-6-S2-S5,PMC2981881,21067547,CC BY,"Viruses are fast evolving pathogens that continuously adapt to the highly variable environments they live and reproduce in. Strategies devoted to inhibit virus replication and to control their spread among hosts need to cope with these extremely heterogeneous populations and with their potential to avoid medical interventions. Computational techniques such as phylogenetic methods have broadened our picture of viral evolution both in time and space, and mathematical modeling has contributed substantially to our progress in unraveling the dynamics of virus replication, fitness, and virulence. Integration of multiple computational and mathematical approaches with experimental data can help to predict the behavior of viral pathogens and to anticipate their escape dynamics. This piece of information plays a critical role in some aspects of vaccine development, such as viral strain selection for vaccinations or rational attenuation of viruses. Here we review several aspects of viral evolution that can be addressed quantitatively, and we discuss computational methods that have the potential to improve vaccine design.",2010 Nov 3,"['Ojosnegros, Samuel', 'Beerenwinkel, Niko']",Immunome Res,,,True
2e6797f37268c2339ab73addc0e9ef77efd3c557,PMC,Pro-inflammatory cytokines derived from West Nile virus (WNV)-infected SK-N-SH cells mediate neuroinflammatory markers and neuronal death,http://dx.doi.org/10.1186/1742-2094-7-73,PMC2984415,21034511,CC BY,"BACKGROUND: WNV-associated encephalitis (WNVE) is characterized by increased production of pro-inflammatory mediators, glial cells activation and eventual loss of neurons. WNV infection of neurons is rapidly progressive and destructive whereas infection of non-neuronal brain cells is limited. However, the role of neurons and pathological consequences of pro-inflammatory cytokines released as a result of WNV infection is unclear. Therefore, the objective of this study was to examine the role of key cytokines secreted by WNV-infected neurons in mediating neuroinflammatory markers and neuronal death. METHODS: A transformed human neuroblastoma cell line, SK-N-SH, was infected with WNV at multiplicity of infection (MOI)-1 and -5, and WNV replication kinetics and expression profile of key pro-inflammatory cytokines were analyzed by plaque assay, qRT-PCR, and ELISA. Cell death was measured in SK-N-SH cell line in the presence and absence of neutralizing antibodies against key pro-inflammatory cytokines using cell viability assay, TUNEL and flow cytometry. Further, naïve primary astrocytes were treated with UV-inactivated supernatant from mock- and WNV-infected SK-N-SH cell line and the activation of astrocytes was measured using flow cytometry and ELISA. RESULTS: WNV-infected SK-N-SH cells induced the expression of IL-1β, -6, -8, and TNF-α in a dose- and time-dependent manner, which coincided with increase in virus-induced cell death. Treatment of cells with anti-IL-1β or -TNF-α resulted in significant reduction of the neurotoxic effects of WNV. Furthermore treatment of naïve astrocytes with UV-inactivated supernatant from WNV-infected SK-N-SH cell line increased expression of glial fibrillary acidic protein and key inflammatory cytokines. CONCLUSION: Our results for the first time suggest that neurons are one of the potential sources of pro-inflammatory cytokines in WNV-infected brain and these neuron-derived cytokines contribute to WNV-induced neurotoxicity. Moreover, cytokines released from neurons also mediate the activation of astrocytes. Our data define specific role(s) of WNV-induced pro-inflammatory cytokines and provide a framework for the development of anti-inflammatory drugs as much-needed therapeutic interventions to limit symptoms associated with WNVE.",2010 Oct 31,"['Kumar, Mukesh', 'Verma, Saguna', 'Nerurkar, Vivek R']",J Neuroinflammation,,,True
fadf1a77d8e94ac8611eb79cf4d0da59872d72bb,PMC,Failure of Fluid Absorption in the Endolymphatic Sac Initiates Cochlear Enlargement that Leads to Deafness in Mice Lacking Pendrin Expression,http://dx.doi.org/10.1371/journal.pone.0014041,PMC2984494,21103348,CC BY,"Mutations of SLC26A4 are among the most prevalent causes of hereditary deafness. Deafness in the corresponding mouse model, Slc26a4(−/−), results from an abnormally enlarged cochlear lumen. The goal of this study was to determine whether the cochlear enlargement originates with defective cochlear fluid transport or with a malfunction of fluid transport in the connected compartments, which are the vestibular labyrinth and the endolymphatic sac. Embryonic inner ears from Slc26a4(+/−) and Slc26a4(−/−) mice were examined by confocal microscopy ex vivo or after 2 days of organ culture. Culture allowed observations of intact, ligated or partially resected inner ears. Cochlear lumen formation was found to begin at the base of the cochlea between embryonic day (E) 13.5 and 14.5. Enlargement was immediately evident in Slc26a4(−/−) compared to Slc26a4(+/−) mice. In Slc26a4(+/−) and Slc26a4(−/−) mice, separation of the cochlea from the vestibular labyrinth by ligation at E14.5 resulted in a reduced cochlear lumen. Resection of the endolymphatic sacs at E14.5 led to an enlarged cochlear lumen in Slc26a4(+/−) mice but caused no further enlargement of the already enlarged cochlear lumen in Slc26a4(−/−) mice. Ligation or resection performed later, at E17.5, did not alter the cochlea lumen. In conclusion, the data suggest that cochlear lumen formation is initiated by fluid secretion in the vestibular labyrinth and temporarily controlled by fluid absorption in the endolymphatic sac. Failure of fluid absorption in the endolymphatic sac due to lack of Slc26a4 expression appears to initiate cochlear enlargement in mice, and possibly humans, lacking functional Slc26a4 expression.",2010 Nov 17,"['Kim, Hyoung-Mi', 'Wangemann, Philine']",PLoS One,,,True
4be572af41fbf94759bf8872ff257fa0f632dca0,PMC,Network Analysis of Global Influenza Spread,http://dx.doi.org/10.1371/journal.pcbi.1001005,PMC2987833,21124942,CC BY,"Although vaccines pose the best means of preventing influenza infection, strain selection and optimal implementation remain difficult due to antigenic drift and a lack of understanding global spread. Detecting viral movement by sequence analysis is complicated by skewed geographic and seasonal distributions in viral isolates. We propose a probabilistic method that accounts for sampling bias through spatiotemporal clustering and modeling regional and seasonal transmission as a binomial process. Analysis of H3N2 not only confirmed East-Southeast Asia as a source of new seasonal variants, but also increased the resolution of observed transmission to a country level. H1N1 data revealed similar viral spread from the tropics. Network analysis suggested China and Hong Kong as the origins of new seasonal H3N2 strains and the United States as a region where increased vaccination would maximally disrupt global spread of the virus. These techniques provide a promising methodology for the analysis of any seasonal virus, as well as for the continued surveillance of influenza.",2010 Nov 18,"['Chan, Joseph', 'Holmes, Antony', 'Rabadan, Raul']",PLoS Comput Biol,,,True
b1ec83bddfe11fc5f176972ca4ae358b4f46c79f,PMC,Potent and persistent antibody responses against the receptor-binding domain of SARS-CoV spike protein in recovered patients,http://dx.doi.org/10.1186/1743-422X-7-299,PMC2988023,21047436,CC BY,"BACKGROUND: The spike (S) protein of SARS-CoV not only mediates receptor-binding but also induces neutralizing antibodies. We previously identified the receptor-binding domain (RBD) of S protein as a major target of neutralizing antibodies in animal models and thus proposed a RBD-based vaccine. However, the antigenicity and immunogenicity of RBD in humans need to be characterized. RESULTS: Two panels of serum samples from recovered SARS patients were included and the antibody responses against the RBD were measured by ELISA and micro-neutralization assays. We found that the RBD of S protein induced potent antibody responses in the recovered SARS patients and RBD-specific antibodies could persist at high titers over three year follow-up. Furthermore, affinity purified anti-RBD antibodies possessed robust neutralizing activity. CONCLUSION: The RBD of SARS-CoV is highly immunogenic in humans and mediates protective responses and RBD-based vaccines and diagnostic approaches can be further developed.",2010 Nov 4,"['Cao, Zhiliang', 'Liu, Lifeng', 'Du, Lanying', 'Zhang, Chao', 'Jiang, Shibo', 'Li, Taisheng', 'He, Yuxian']",Virol J,,,True
357a008270023e621d758ada372b14e676edb782,PMC,Facing the threat of influenza pandemic - roles of and implications to general practitioners,http://dx.doi.org/10.1186/1471-2458-10-661,PMC2988738,21044300,CC BY,"The 2009 pandemic of H1N1 influenza, compounded with seasonal influenza, posed a global challenge. Despite the announcement of post-pandemic period on 10 August 2010 by theWHO, H1N1 (2009) virus would continue to circulate as a seasonal virus for some years and national health authorities should remain vigilant due to unpredictable behaviour of the virus. Majority of the world population is living in countries with inadequate resources to purchase vaccines and stockpile antiviral drugs. Basic hygienic measures such as wearing face masks and the hygienic practice of hand washing could reduce the spread of the respiratory viruses. However, the imminent issue is translating these measures into day-to-day practice. The experience from Severe Acute Respiratory Syndrome (SARS) in Hong Kong has shown that general practitioners (GPs) were willing to discharge their duties despite risks of getting infected themselves. SARS event has highlighted the inadequate interface between primary and secondary care and valuable health care resources were thus inappropriately matched to community needs. There are various ways for GPs to contribute in combating the influenza pandemic. They are prompt in detecting and monitoring epidemics and mini-epidemics of viral illnesses in the community. They can empower and raise the health literacy of the community such as advocating personal hygiene and other precautious measures. GPs could also assist in the development of protocols for primary care management of patients with flu-like illnesses and conduct clinical audits on the standards of preventive and treatment measures. GPs with adequate liaison with public health agencies would facilitate early diagnosis of patients with influenza. In this article, we summarise the primary care actions for phases 4-6 of the pandemic. We shall discuss the novel roles of GPs as alternative source of health care for patients who would otherwise be cared for in the secondary care level. The health care system would thus remain sustainable during the public health crisis.",2010 Nov 2,"['Lee, Albert', 'Chuh, Antonio AT']",BMC Public Health,,,True
9f27a960236a99c8b1dc60e71e111257a1d5e862,PMC,Sequencing of DC-SIGN promoter indicates an association between promoter variation and risk of nasopharyngeal carcinoma in cantonese,http://dx.doi.org/10.1186/1471-2350-11-161,PMC2989958,21067616,CC BY,BACKGROUND: The dendritic cell-specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) is an important pathogen recognition receptor of the innate immune system. DC-SIGN promoter variants play important role in the susceptibility to various infectious diseases. Nasopharyngeal carcinoma (NPC) is a malignancy that is common in southern China and whether DC-SIGN promoter variants have effects on susceptibility to NPC is still unknown. The aim of this study is to ascertain the potential involvement of DC-SIGN promoter single nucleotide polymorphisms (SNPs) in NPC susceptibility. METHODS: We conducted a case control study based on Cantonese population including 444 NPC patients and 464 controls matched on age and sex. The 1041 bp of DC-SIGN promoter region was directly sequenced for all samples. Sequence alignment and SNP search were inspected using DNAStar analysis programs and haplotype frequencies were estimated in Haploview V 4.0. The associations between the SNPs and the risk of NPC were analyzed using chi-square test and non-conditional logistic regression analysis with SPSS 13.0 software. RESULTS: A total of six variants were observed in the DC-SIGN promoter region and DC-SIGN -139 GG and -939 AA were significantly associated with NPC risk with adjusted Odds Ratios (ORs) of 2.10 (95% confidence interval [CI] = 1.23-3.59; P = 0.006) and 2.52 (1.29-4.93; P = 0.007) respectively and subjects carrying the risk allele DC-SIGN -871 G had 1.47-fold (95% CI = 1.14-1.90) increased risks of developing NPC (P = 0.003). Haplotype analysis revealed that h1 'AAAG' was significantly associated with protection against NPC (OR = 0.69; P = 0.0002) and the association was still significant when using 1000 permutation test runs (P = 0.001). CONCLUSIONS: Our study indicated that DC-SIGN promoter variants appear to be involved in the susceptibility to NPC and the detailed mechanism of this effect need further studies.,2010 Nov 11,"['Xu, Ya-Fei', 'Liu, Wan-Li', 'Dong, Ju-Qin', 'Liu, Wen-Sheng', 'Feng, Qi-Sheng', 'Chen, Li-Zhen', 'Zeng, Yi-Xin', 'Zeng, Mu-Sheng', 'Jia, Wei-Hua']",BMC Med Genet,,,True
fd5e3020671499cde830bd25de618009ece0af13,PMC,Antiviral and Neuroprotective Role of Octaguanidinium Dendrimer-Conjugated Morpholino Oligomers in Japanese Encephalitis,http://dx.doi.org/10.1371/journal.pntd.0000892,PMC2990691,21124882,CC BY,"BACKGROUND: Japanese encephalitis (JE), caused by a mosquito-borne flavivirus, is endemic to the entire south-east Asian and adjoining regions. Currently no therapeutic interventions are available for JE, thereby making it one of the most dreaded encephalitides in the world. An effective way to counter the virus would be to inhibit viral replication by using anti-sense molecules directed against the viral genome. Octaguanidinium dendrimer-conjugated Morpholino (or Vivo-Morpholino) are uncharged anti-sense oligomers that can enter cells of living organisms by endocytosis and subsequently escape from endosomes into the cytosol/nuclear compartment of cells. We hypothesize that Vivo-Morpholinos generated against specific regions of 3′ or 5′ untranslated regions of JEV genome, when administered in an experimental model of JE, will have significant antiviral and neuroprotective effect. METHODOLOGY/PRINCIPAL FINDINGS: Mice were infected with JEV (GP78 strain) followed by intraperitoneal administration of Morpholinos (5 mg/kg body weight) daily for up to five treatments. Survivability of the animals was monitored for 15 days (or until death) following which they were sacrificed and their brains were processed either for immunohistochemical staining or protein extraction. Plaque assay and immunoblot analysis performed from brain homogenates showed reduced viral load and viral protein expression, resulting in greater survival of infected animals. Neuroprotective effect was observed by thionin staining of brain sections. Cytokine bead array showed reduction in the levels of proinflammatory cytokines in brain following Morpholino treatment, which were elevated after infection. This corresponded to reduced microglial activation in brain. Oxidative stress was reduced and certain stress-related signaling molecules were found to be positively modulated following Morpholino treatment. In vitro studies also showed that there was decrease in infective viral particle production following Morpholino treatment. CONCLUSIONS/SIGNIFICANCE: Administration of Vivo-Morpholino effectively resulted in increased survival of animals and neuroprotection in a murine model of JE. Hence, these oligomers represent a potential antiviral agent that merits further evaluation.",2010 Nov 23,"['Nazmi, Arshed', 'Dutta, Kallol', 'Basu, Anirban']",PLoS Negl Trop Dis,,,True
bbd8195f35ba4648be5eb649a3038f7485b7a71e,PMC,"General hospital staff worries, perceived sufficiency of information and associated psychological distress during the A/H1N1 influenza pandemic",http://dx.doi.org/10.1186/1471-2334-10-322,PMC2990753,21062471,CC BY,"BACKGROUND: Health care workers (HCWs) presented frequent concerns regarding their health and their families' health and high levels of psychological distress during previous disease outbreaks, such as the SARS outbreak, which was associated with social isolation and intentional absenteeism. We aimed to assess HCWs concerns and anxiety, perceived sufficiency of information, and intended behavior during the recent A/H1N1 influenza pandemic and their associations with psychological distress. METHOD: Between September 1(st )and 30(th), 2009, 469 health-care workers (HCWs) of a tertiary teaching hospital completed a 20-item questionnaire regarding concerns and worries about the new A/H1N1 influenza pandemic, along with Cassileth's Information Styles Questionnaire (part-I) and the GHQ-28. RESULTS: More than half of the present study's HCWs (56.7%) reported they were worried about the A/H1N1 influenza pandemic, their degree of anxiety being moderately high (median 6/9). The most frequent concern was infection of family and friends and the health consequences of the disease (54.9%). The perceived risk of being infected was considered moderately high (median 6/9). Few HCWs (6.6%) had restricted their social contacts and fewer (3.8%) felt isolated by their family members and friends because of their hospital work, while a low percentage (4.3%) indented to take a leave to avoid infection. However, worry and degree of worry were significantly associated with intended absenteeism (p < 0.0005), restriction of social contacts (p < 0.0005), and psychological distress (p = 0.036). Perceived sufficiency of information about several aspects of the A/H1N1 influenza was moderately high, and the overall information about the A/H1N1 influenza was considered clear (median 7.4/9). Also, perceived sufficiency of information for the prognosis of the infection was significantly independently associated with the degree of worry about the pandemic (p = 0.008). CONCLUSIONS: A significant proportion of HCWs experienced moderately high anxiety about the pandemic, and their degree of worry was an independent correlate of psychological distress. Since perceived sufficiency of information about the A/H1N1 influenza prognosis was associated with reduced degree of worry, hospital managers and consultation-liaison psychiatry services should try to provide for HCWs' need for information, in order to offer favourable working conditions in times of extreme distress, such as the current and future pandemics.",2010 Nov 9,"['Goulia, Panagiota', 'Mantas, Christos', 'Dimitroula, Danai', 'Mantis, Dimitrios', 'Hyphantis, Thomas']",BMC Infect Dis,,,True
248e6ce743867edebd9fb8d241a56f542732888a,PMC,Antiviral Lead Compounds from Marine Sponges,http://dx.doi.org/10.3390/md8102619,PMC2992996,21116410,CC BY,"Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hopedto be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed.",2010 Oct 11,"['Sagar, Sunil', 'Kaur, Mandeep', 'Minneman, Kenneth P.']",Mar Drugs,,,True
e806597d3525be5b55b7bd8812217c2e53bced9f,PMC,A Functional Henipavirus Envelope Glycoprotein Pseudotyped Lentivirus Assay System,http://dx.doi.org/10.1186/1743-422X-7-312,PMC2994542,21073718,CC BY,"BACKGROUND: Hendra virus (HeV) and Nipah virus (NiV) are newly emerged zoonotic paramyxoviruses discovered during outbreaks in Queensland, Australia in 1994 and peninsular Malaysia in 1998/9 respectively and classified within the new Henipavirus genus. Both viruses can infect a broad range of mammalian species causing severe and often-lethal disease in humans and animals, and repeated outbreaks continue to occur. Extensive laboratory studies on the host cell infection stage of HeV and NiV and the roles of their envelope glycoproteins have been hampered by their highly pathogenic nature and restriction to biosafety level-4 (BSL-4) containment. To circumvent this problem, we have developed a henipavirus envelope glycoprotein pseudotyped lentivirus assay system using either a luciferase gene or green fluorescent protein (GFP) gene encoding human immunodeficiency virus type-1 (HIV-1) genome in conjunction with the HeV and NiV fusion (F) and attachment (G) glycoproteins. RESULTS: Functional retrovirus particles pseudotyped with henipavirus F and G glycoproteins displayed proper target cell tropism and entry and infection was dependent on the presence of the HeV and NiV receptors ephrinB2 or B3 on target cells. The functional specificity of the assay was confirmed by the lack of reporter-gene signals when particles bearing either only the F or only G glycoprotein were prepared and assayed. Virus entry could be specifically blocked when infection was carried out in the presence of a fusion inhibiting C-terminal heptad (HR-2) peptide, a well-characterized, cross-reactive, neutralizing human mAb specific for the henipavirus G glycoprotein, and soluble ephrinB2 and B3 receptors. In addition, the utility of the assay was also demonstrated by an examination of the influence of the cytoplasmic tail of F in its fusion activity and incorporation into pseudotyped virus particles by generating and testing a panel of truncation mutants of NiV and HeV F. CONCLUSIONS: Together, these results demonstrate that a specific henipavirus entry assay has been developed using NiV or HeV F and G glycoprotein pseudotyped reporter-gene encoding retrovirus particles. This assay can be conducted safely under BSL-2 conditions and will be a useful tool for measuring henipavirus entry and studying F and G glycoprotein function in the context of virus entry, as well as in assaying and characterizing neutralizing antibodies and virus entry inhibitors.",2010 Nov 12,"['Khetawat, Dimple', 'Broder, Christopher C']",Virol J,,,True
b9881ca556b8d6e74c2fe3b9c2195429fcb0d09d,PMC,H1N1pdm Influenza Infection in Hospitalized Cancer Patients: Clinical Evolution and Viral Analysis,http://dx.doi.org/10.1371/journal.pone.0014158,PMC2994772,21152402,CC0,"BACKGROUND: The novel influenza A pandemic virus (H1N1pdm) caused considerable morbidity and mortality worldwide in 2009. The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil. METHODS: We performed a prospective single-center cohort study in a cancer center in Rio de Janeiro, Brazil. Hospitalized patients with cancer and a confirmed diagnosis of influenza A H1N1pdm were evaluated. The main outcome measures in this study were in-hospital mortality, duration of viral shedding, viral persistence and both functional and molecular analyses of H1N1pdm susceptibility to oseltamivir. RESULTS: A total of 44 hospitalized patients with suspected influenza-like illness were screened. A total of 24 had diagnosed H1N1pdm infections. The overall hospital mortality in our cohort was 21%. Thirteen (54%) patients required intensive care. The median age of the studied cohort was 14.5 years (3–69 years). Eighteen (75%) patients had received chemotherapy in the previous month, and 14 were neutropenic at the onset of influenza. A total of 10 patients were evaluated for their duration of viral shedding, and 5 (50%) displayed prolonged viral shedding (median 23, range = 11–63 days); however, this was not associated with the emergence of a resistant H1N1pdm virus. Viral evolution was observed in sequentially collected samples. CONCLUSIONS: Prolonged influenza A H1N1pdm shedding was observed in cancer patients. However, oseltamivir resistance was not detected. Taken together, our data suggest that severely ill cancer patients may constitute a pandemic virus reservoir with major implications for viral propagation.",2010 Nov 30,"['Souza, Thiago Moreno L.', 'Salluh, Jorge I. F.', 'Bozza, Fernando A.', 'Mesquita, Milene', 'Soares, Márcio', 'Motta, Fernando C.', 'Pitrowsky, Melissa Tassano', 'de Lourdes Oliveira, Maria', 'Mishin, Vasiliy P.', 'Gubareva, Larissa V.', 'Whitney, Anne', 'Rocco, Sandra Amaral', 'Gonçalves, Vânia Maria C.', 'Marques, Venceslaine Prado', 'Velasco, Eduardo', 'Siqueira, Marilda M.']",PLoS One,,,True
f4f804bac7b32c84ad6572776df684df2a2e5fda,PMC,Livestock Drugs and Disease: The Fatal Combination behind Breeding Failure in Endangered Bearded Vultures,http://dx.doi.org/10.1371/journal.pone.0014163,PMC2994777,21152405,CC BY,"There is increasing concern about the impact of veterinary drugs and livestock pathogens as factors damaging wildlife health, especially of threatened avian scavengers feeding upon medicated livestock carcasses. We conducted a comprehensive study of failed eggs and dead nestlings in bearded vultures (Gypaetus barbatus) to attempt to elucidate the proximate causes of breeding failure behind the recent decline in productivity in the Spanish Pyrenees. We found high concentrations of multiple veterinary drugs, primarily fluoroquinolones, in most failed eggs and nestlings, associated with multiple internal organ damage and livestock pathogens causing disease, especially septicaemia by swine pathogens and infectious bursal disease. The combined impact of drugs and disease as stochastic factors may result in potentially devastating effects exacerbating an already high risk of extinction and should be considered in current conservation programs for bearded vultures and other scavenger species, especially in regards to dangerous veterinary drugs and highly pathogenic poultry viruses.",2010 Nov 30,"['Blanco, Guillermo', 'Lemus, Jesús A.']",PLoS One,,,True
268d325d7a8003c4b0474e6a605d6655ab370b6f,PMC,Contact Heterogeneity and Phylodynamics: How Contact Networks Shape Parasite Evolutionary Trees,http://dx.doi.org/10.1155/2011/238743,PMC2995904,21151699,CC BY,"The inference of population dynamics from molecular sequence data is becoming an important new method for the surveillance of infectious diseases. Here, we examine how heterogeneity in contact shapes the genealogies of parasitic agents. Using extensive simulations, we find that contact heterogeneity can have a strong effect on how the structure of genealogies reflects epidemiologically relevant quantities such as the proportion of a population that is infected. Comparing the simulations to BEAST reconstructions, we also find that contact heterogeneity can increase the number of sequence isolates required to estimate these quantities over the course of an epidemic. Our results suggest that data about contact-network structure will be required in addition to sequence data for accurate estimation of a parasitic agent's genealogy. We conclude that network models will be important for progress in this area.",2011 Dec 1,"[""O'Dea, Eamon B."", 'Wilke, Claus O.']",Interdiscip Perspect Infect Dis,,,True
97e07d83db421faee2a7a42a0e2c8a117c08b016,PMC,Light whole genome sequence for SNP discovery across domestic cat breeds,http://dx.doi.org/10.1186/1471-2164-11-406,PMC2996934,20576142,CC BY,"BACKGROUND: The domestic cat has offered enormous genomic potential in the veterinary description of over 250 hereditary disease models as well as the occurrence of several deadly feline viruses (feline leukemia virus -- FeLV, feline coronavirus -- FECV, feline immunodeficiency virus - FIV) that are homologues to human scourges (cancer, SARS, and AIDS respectively). However, to realize this bio-medical potential, a high density single nucleotide polymorphism (SNP) map is required in order to accomplish disease and phenotype association discovery. DESCRIPTION: To remedy this, we generated 3,178,297 paired fosmid-end Sanger sequence reads from seven cats, and combined these data with the publicly available 2X cat whole genome sequence. All sequence reads were assembled together to form a 3X whole genome assembly allowing the discovery of over three million SNPs. To reduce potential false positive SNPs due to the low coverage assembly, a low upper-limit was placed on sequence coverage and a high lower-limit on the quality of the discrepant bases at a potential variant site. In all domestic cats of different breeds: female Abyssinian, female American shorthair, male Cornish Rex, female European Burmese, female Persian, female Siamese, a male Ragdoll and a female African wildcat were sequenced lightly. We report a total of 964 k common SNPs suitable for a domestic cat SNP genotyping array and an additional 900 k SNPs detected between African wildcat and domestic cats breeds. An empirical sampling of 94 discovered SNPs were tested in the sequenced cats resulting in a SNP validation rate of 99%. CONCLUSIONS: These data provide a large collection of mapped feline SNPs across the cat genome that will allow for the development of SNP genotyping platforms for mapping feline diseases.",2010 Jun 24,"['Mullikin, James C', 'Hansen, Nancy F', 'Shen, Lei', 'Ebling, Heather', 'Donahue, William F', 'Tao, Wei', 'Saranga, David J', 'Brand, Adrianne', 'Rubenfield, Marc J', 'Young, Alice C', 'Cruz, Pedro', 'Driscoll, Carlos', 'David, Victor', 'Al-Murrani, Samer WK', 'Locniskar, Mary F', 'Abrahamsen, Mitchell S', ""O'Brien, Stephen J"", 'Smith, Douglas R', 'Brockman, Jeffrey A']",BMC Genomics,,,True
c7c91a1ce95ce401750cb856d14d48683a0e4fb7,PMC,Hierarchical Clustering Using the Arithmetic-Harmonic Cut: Complexity and Experiments,http://dx.doi.org/10.1371/journal.pone.0014067,PMC2997101,21151943,CC BY,"Clustering, particularly hierarchical clustering, is an important method for understanding and analysing data across a wide variety of knowledge domains with notable utility in systems where the data can be classified in an evolutionary context. This paper introduces a new hierarchical clustering problem defined by a novel objective function we call the arithmetic-harmonic cut. We show that the problem of finding such a cut is [Image: see text]-hard and [Image: see text]-hard but is fixed-parameter tractable, which indicates that although the problem is unlikely to have a polynomial time algorithm (even for approximation), exact parameterized and local search based techniques may produce workable algorithms. To this end, we implement a memetic algorithm for the problem and demonstrate the effectiveness of the arithmetic-harmonic cut on a number of datasets including a cancer type dataset and a corona virus dataset. We show favorable performance compared to currently used hierarchical clustering techniques such as [Image: see text]-Means, Graclus and Normalized-Cut. The arithmetic-harmonic cut metric overcoming difficulties other hierarchal methods have in representing both intercluster differences and intracluster similarities.",2010 Dec 2,"['Rizzi, Romeo', 'Mahata, Pritha', 'Mathieson, Luke', 'Moscato, Pablo']",PLoS One,,,True
621c17ebf69617fe8e330f6c9818880902ee6a97,PMC,Public views of the uk media and government reaction to the 2009 swine flu pandemic,http://dx.doi.org/10.1186/1471-2458-10-697,PMC2998491,21078169,CC BY,"BACKGROUND: The first cases of influenza A/H1N1 (swine flu) were confirmed in the UK on 27th April 2009, after a novel virus first identified in Mexico rapidly evolved into a pandemic. The swine flu outbreak was the first pandemic in more than 40 years and for many, their first encounter with a major influenza outbreak. This study examines public understandings of the pandemic, exploring how people deciphered the threat and perceived they could control the risks. METHODS: Purposive sampling was used to recruit seventy three people (61 women and 12 men) to take part in 14 focus group discussions around the time of the second wave in swine flu cases. RESULTS: These discussions showed that there was little evidence of the public over-reacting, that people believed the threat of contracting swine flu was inevitable, and that they assessed their own self-efficacy for protecting against it to be low. Respondents assessed a greater risk to their health from the vaccine than from the disease. Such findings could have led to apathy about following the UK Governments recommended health protective behaviours, and a sub-optimal level of vaccine uptake. More generally, people were confused about the difference between seasonal influenza and swine flu and their vaccines. CONCLUSIONS: This research suggests a gap in public understandings which could hinder attempts to communicate about novel flu viruses in the future. There was general support for the government's handling of the pandemic, although its public awareness campaign was deemed ineffectual as few people changed their current hand hygiene practices. There was less support for the media who were deemed to have over-reported the swine flu pandemic.",2010 Nov 15,"['Hilton, Shona', 'Smith, Emily']",BMC Public Health,,,True
2cb75a42281bf540c142bec979a4bc66da597a3a,PMC,Association of residential dampness and mold with respiratory tract infections and bronchitis: a meta-analysis,http://dx.doi.org/10.1186/1476-069X-9-72,PMC3000394,21078183,CC BY,"BACKGROUND: Dampness and mold have been shown in qualitative reviews to be associated with a variety of adverse respiratory health effects, including respiratory tract infections. Several published meta-analyses have provided quantitative summaries for some of these associations, but not for respiratory infections. Demonstrating a causal relationship between dampness-related agents, which are preventable exposures, and respiratory tract infections would suggest important new public health strategies. We report the results of quantitative meta-analyses of published studies that examined the association of dampness or mold in homes with respiratory infections and bronchitis. METHODS: For primary studies meeting eligibility criteria, we transformed reported odds ratios (ORs) and confidence intervals (CIs) to the log scale. Both fixed and random effects models were applied to the log ORs and their variances. Most studies contained multiple estimated ORs. Models accounted for the correlation between multiple results within the studies analyzed. One set of analyses was performed with all eligible studies, and another set restricted to studies that controlled for age, gender, smoking, and socioeconomic status. Subgroups of studies were assessed to explore heterogeneity. Funnel plots were used to assess publication bias. RESULTS: The resulting summary estimates of ORs from random effects models based on all studies ranged from 1.38 to 1.50, with 95% CIs excluding the null in all cases. Use of different analysis models and restricting analyses based on control of multiple confounding variables changed findings only slightly. ORs (95% CIs) from random effects models using studies adjusting for major confounding variables were, for bronchitis, 1.45 (1.32-1.59); for respiratory infections, 1.44 (1.31-1.59); for respiratory infections excluding nonspecific upper respiratory infections, 1.50 (1.32-1.70), and for respiratory infections in children or infants, 1.48 (1.33-1.65). Little effect of publication bias was evident. Estimated attributable risk proportions ranged from 8% to 20%. CONCLUSIONS: Residential dampness and mold are associated with substantial and statistically significant increases in both respiratory infections and bronchitis. If these associations were confirmed as causal, effective control of dampness and mold in buildings would prevent a substantial proportion of respiratory infections.",2010 Nov 15,"['Fisk, William J', 'Eliseeva, Ekaterina A', 'Mendell, Mark J']",Environ Health,,,True
e8e766af194b641ae3a9636379a18515c053ae65,PMC,Human monoclonal IgG selection of Plasmodium falciparum for the expression of placental malaria-specific variant surface antigens,http://dx.doi.org/10.1111/j.1365-3024.2009.01097.x,PMC3001033,19493213,CC BY,Pregnancy-associatedPlasmodium falciparum malaria (PAM) is a major cause of morbidity and mortality in African women and their offspring. PAM is characterized by accumulation of infected erythrocytes (IEs) that adhere to chondroitin sulphate A (CSA) in the placental intervillous space. We show here that human monoclonal IgG antibodies with specificity for variant surface antigens (VSA) specifically expressed by CSA-adhering IEs (VSA(PAM)) can be used in vitro to select parasites from nonpregnant donors to express VSA(PAM) and that this selection for VSA(PAM) expression results in preferential transcription of var2csa. The results corroborate current efforts to develop PAM-specific vaccines based on VAR2CSA.,2009 Jun,"['SOERLI, J', 'BARFOD, L', 'LAVSTSEN, T', 'BERNASCONI, N L', 'LANZAVECCHIA, A', 'HVIID, L']",Parasite Immunol,,,True
a64149dbac768a5fac5c4ca620c09c2dea2e2bf0,PMC,"Travel and migration associated infectious diseases morbidity in Europe, 2008",http://dx.doi.org/10.1186/1471-2334-10-330,PMC3001727,21083874,CC BY,"BACKGROUND: Europeans represent the majority of international travellers and clinicians encountering returned patients have an essential role in recognizing, and communicating travel-associated public health risks. METHODS: To investigate the morbidity of travel associated infectious diseases in European travellers, we analysed diagnoses with demographic, clinical and travel-related predictors of disease, in 6957 ill returned travellers who presented in 2008 to EuroTravNet centres with a presumed travel associated condition. RESULTS: Gastro-intestinal (GI) diseases accounted for 33% of illnesses, followed by febrile systemic illnesses (20%), dermatological conditions (12%) and respiratory illnesses (8%). There were 3 deaths recorded; a sepsis caused by Escherichia coli pyelonephritis, a dengue shock syndrome and a Plasmodium falciparum malaria. GI conditions included bacterial acute diarrhea (6.9%), as well as giardiasis and amebasis (2.3%). Among febrile systemic illnesses with identified pathogens, malaria (5.4%) accounted for most cases followed by dengue (1.9%) and others including chikungunya, rickettsial diseases, leptospirosis, brucellosis, Epstein Barr virus infections, tick-borne encephalitis (TBE) and viral hepatitis. Dermatological conditions were dominated by bacterial infections, arthropod bites, cutaneous larva migrans and animal bites requiring rabies post-exposure prophylaxis and also leishmaniasis, myasis, tungiasis and one case of leprosy. Respiratory illness included 112 cases of tuberculosis including cases of multi-drug resistant or extensively drug resistant tuberculosis, 104 cases of influenza like illness, and 5 cases of Legionnaires disease. Sexually transmitted infections (STI) accounted for 0.6% of total diagnoses and included HIV infection and syphilis. A total of 165 cases of potentially vaccine preventable diseases were reported. Purpose of travel and destination specific risk factors was identified for several diagnoses such as Chagas disease in immigrant travellers from South America and P. falciparum malaria in immigrants from sub-Saharan Africa. Travel within Europe was also associated with health risks with distinctive profiles for Eastern and Western Europe. CONCLUSIONS: In 2008, a broad spectrum of travel associated diseases were diagnosed at EuroTravNet core sites. Diagnoses varied according to regions visited by ill travellers. The spectrum of travel associated morbidity also shows that there is a need to dispel the misconception that travel, close to home, in Europe, is without significant health risk.",2010 Nov 17,"['Field, Vanessa', 'Gautret, Philippe', 'Schlagenhauf, Patricia', 'Burchard, Gerd-Dieter', 'Caumes, Eric', 'Jensenius, Mogens', 'Castelli, Francesco', 'Gkrania-Klotsas, Effrossyni', 'Weld, Leisa', 'Lopez-Velez, Rogelio', 'de Vries, Peter', 'von Sonnenburg, Frank', 'Loutan, Louis', 'Parola, Philippe']",BMC Infect Dis,,,True
70f03de789f72ae5b9709cb6bef62c10ab8dcdef,PMC,Flocked nasal swab versus nasopharyngeal aspirate for detection of respiratory tract viruses in immunocompromised adults: a matched comparative study,http://dx.doi.org/10.1186/1471-2334-10-340,PMC3001728,21110854,CC BY,"BACKGROUND: Several studies have compared nasal swabs to the more invasive nasopharyngeal aspirate (NPA) for detection of respiratory viruses. Mostly, the comparisons have been performed on immunocompetent children with upper respiratory tract symptoms. The results range from a relatively poor sensitivity for the swabs to an even higher sensitivity than for the NPA. We aimed to investigate the sensitivity of a flocked nasal swab (fNS) on immunocompromised adults with febrile neutropenia. METHODS: During 16 months, adults with a hematological disorder presenting with febrile neutropenia were enrolled in the study. Paired samples of the fNS and NPA were collected in the outer part of the nasal cavity and the nasopharynx, respectively. The samples were analyzed regarding a panel of 15 respiratory viruses by means of quantitative polymerase chain reaction. Furthermore, as an indirect measure of cell yield by either method, the copy number of the human beta actin gene was also determined. Cohen's kappa was calculated as a measure of agreement of the results obtained from either method. Wilcoxon signed-rank test was used for comparison of cell yield. RESULTS: A total of 98 paired samples from a total of 89 patients were collected. Twenty of the pairs had virus detected in at least one of the specimens; 11 in both, 7 in NPA only, and 2 in fNS only. For the fNS, the overall sensitivity for any virus and for rhinovirus only was 65% and 78%, respectively. NPA was significantly superior to the fNS in collecting epithelial cells. CONCLUSION: We found the overall sensitivity of 65% to be too low to replace NPA with this sampling technique in this patient category.",2010 Nov 26,"['Öhrmalm, Lars', 'Wong, Michelle', 'Rotzén-Östlund, Maria', 'Norbeck, Oscar', 'Broliden, Kristina', 'Tolfvenstam, Thomas']",BMC Infect Dis,,,True
8d8ab6d3f0c6ff09e306c23c87f823f9382ff32e,PMC,Responses of Human Endothelial Cells to Pathogenic and Non-Pathogenic Leptospira Species,http://dx.doi.org/10.1371/journal.pntd.0000918,PMC3001904,21179504,CC BY,"Leptospirosis is a widespread zoonotic infection that primarily affects residents of tropical regions, but causes infections in animals and humans in temperate regions as well. The agents of leptospirosis comprise several members of the genus Leptospira, which also includes non-pathogenic, saprophytic species. Leptospirosis can vary in severity from a mild, non-specific illness to severe disease that includes multi-organ failure and widespread endothelial damage and hemorrhage. To begin to investigate how pathogenic leptospires affect endothelial cells, we compared the responses of two endothelial cell lines to infection by pathogenic versus non-pathogenic leptospires. Microarray analyses suggested that pathogenic L. interrogans and non-pathogenic L. biflexa triggered changes in expression of genes whose products are involved in cellular architecture and interactions with the matrix, but that the changes were in opposite directions, with infection by L. biflexa primarily predicted to increase or maintain cell layer integrity, while L. interrogans lead primarily to changes predicted to disrupt cell layer integrity. Neither bacterial strain caused necrosis or apoptosis of the cells even after prolonged incubation. The pathogenic L. interrogans, however, did result in significant disruption of endothelial cell layers as assessed by microscopy and the ability of the bacteria to cross the cell layers. This disruption of endothelial layer integrity was abrogated by addition of the endothelial protective drug lisinopril at physiologically relevant concentrations. These results suggest that, through adhesion of L. interrogans to endothelial cells, the bacteria may disrupt endothelial barrier function, promoting dissemination of the bacteria and contributing to severe disease manifestations. In addition, supplementing antibiotic therapy with lisinopril or derivatives with endothelial protective activities may decrease the severity of leptospirosis.",2010 Dec 14,"['Martinez-Lopez, Denise G.', 'Fahey, Mark', 'Coburn, Jenifer']",PLoS Negl Trop Dis,,,True
f46d2803581226a9a94026693e95db88e7c70641,PMC,A Porcine Adenovirus with Low Human Seroprevalence Is a Promising Alternative Vaccine Vector to Human Adenovirus 5 in an H5N1 Virus Disease Model,http://dx.doi.org/10.1371/journal.pone.0015301,PMC3002947,21179494,CC BY,"Human adenovirus 5 (AdHu5) vectors are robust vaccine platforms however the presence of naturally-acquired neutralizing antibodies may reduce vector efficacy and potential for re-administration. This study evaluates immune responses and protection following vaccination with a replication-incompetent porcine adenovirus 3 (PAV3) vector as an alternative vaccine to AdHu5 using an avian influenza H5N1 disease model. Vaccine efficacy was evaluated in BALB/c mice following vaccination with different doses of the PAV3 vector expressing an optimized A/Hanoi/30408/2005 H5N1 hemagglutinin antigen (PAV3-HA) and compared with an AdHu5-HA control. PAV3-HA rapidly generated antibody responses, with significant neutralizing antibody titers on day 21, and stronger cellular immune responses detected on day 8, compared to AdHu5-HA. The PAV3-HA vaccine, administered 8 days before challenge, demonstrated improved survival and lower virus load. Evaluation of long-term vaccine efficacy at 12 months post-vaccination showed better protection with the PAV3-HA than with the AdHu5-HA vaccine. Importantly, as opposed to AdHu5, PAV3 vector was not significantly neutralized by human antibodies pooled from over 10,000 individuals. Overall, PAV3-based vector is capable of mediating swift, strong immune responses and offer a promising alternative to AdHu5.",2010 Dec 16,"['Patel, Ami', 'Tikoo, Suresh', 'Kobinger, Gary']",PLoS One,,,True
5bcfcf89e794c73c8d079ddacc6eb7849501b927,PMC,The role of toll-like receptors in acute and chronic lung inflammation,http://dx.doi.org/10.1186/1476-9255-7-57,PMC3003652,21108806,CC BY,"By virtue of its direct contact with the environment, the lung is constantly challenged by infectious and non-infectious stimuli that necessitate a robust yet highly controlled host response coordinated by the innate and adaptive arms of the immune system. Mammalian Toll-like receptors (TLRs) function as crucial sentinels of microbial and non-infectious antigens throughout the respiratory tract and mediate host innate immunity. Selective induction of inflammatory responses to harmful environmental exposures and tolerance to innocuous antigens are required to maintain tissue homeostasis and integrity. Conversely, dysregulated innate immune responses manifest as sustained and self-perpetuating tissue damage rather than controlled tissue repair. In this article we review aspects of Toll-like receptor function that are relevant to the development of acute lung injury and chronic obstructive lung diseases as well as resistance to frequently associated microbial infections.",2010 Nov 25,"['Lafferty, Erin I', 'Qureshi, Salman T', 'Schnare, Markus']",J Inflamm (Lond),,,True
e8c2bc95762a2aefd919b02ae90131bc67716140,PMC,Liposome-Coupled Antigens Are Internalized by Antigen-Presenting Cells via Pinocytosis and Cross-Presented to CD8(+) T Cells,http://dx.doi.org/10.1371/journal.pone.0015225,PMC3003686,21179411,CC BY,"We have previously demonstrated that antigens chemically coupled to the surface of liposomes consisting of unsaturated fatty acids were cross-presented by antigen-presenting cells (APCs) to CD8(+) T cells, and that this process resulted in the induction of antigen-specific cytotoxic T lymphocytes. In the present study, the mechanism by which the liposome-coupled antigens were cross-presented to CD8(+) T cells by APCs was investigated. Confocal laser scanning microscopic analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-based liposomes received processing at both MHC class I and class II compartments, while most of the antigens coupled to the surface of saturated-fatty-acid-based liposomes received processing at the class II compartment. In addition, flow cytometric analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-liposomes were taken up by APCs even in a 4°C environment; this was not true of saturated-fatty-acid-liposomes. When two kinds of inhibitors, dimethylamiloride (DMA) and cytochalasin B, which inhibit pinocytosis and phagocytosis by APCs, respectively, were added to the culture of APCs prior to the antigen pulse, DMA but not cytochalasin B significantly reduced uptake of liposome-coupled antigens. Further analysis of intracellular trafficking of liposomal antigens using confocal laser scanning microscopy revealed that a portion of liposome-coupled antigens taken up by APCs were delivered to the lysosome compartment. In agreement with the reduction of antigen uptake by APCs, antigen presentation by APCs was significantly inhibited by DMA, and resulted in the reduction of IFN-γ production by antigen-specific CD8(+) T cells. These results suggest that antigens coupled to the surface of liposomes consisting of unsaturated fatty acids might be pinocytosed by APCs, loaded onto the class I MHC processing pathway, and presented to CD8(+) T cells. Thus, these liposome-coupled antigens are expected to be applicable for the development of vaccines that induce cellular immunity.",2010 Dec 17,"['Tanaka, Yuriko', 'Taneichi, Maiko', 'Kasai, Michiyuki', 'Kakiuchi, Terutaka', 'Uchida, Tetsuya']",PLoS One,,,True
d3f7afa8b4d0f21b23ccb1135dec12356375f5cc,PMC,Therapeutic Vaccination in Chronic Hepatitis B: Preclinical Studies in the Woodchuck,http://dx.doi.org/10.1155/2010/817580,PMC3003998,21188201,CC BY,"Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to a satisfactory result. Induction of HBV-specific T cells by therapeutic vaccination or immunotherapies may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients did not result in effective control of HBV infection, suggesting that new formulations of therapeutic vaccines are needed. The woodchuck (Marmota monax) is a useful preclinical model for developing the new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments with nucleos(t)ide analogues, DNA vaccines, and protein vaccines were tested in the woodchuck model. In this paper we summarize the available data concerning therapeutic immunization and gene therapy using recombinant viral vectors approaches in woodchucks, which show encouraging results. In addition, we present potential innovations in immunomodulatory strategies to be evaluated in this animal model.",2010 Sep 7,"['Kosinska, Anna D.', 'Zhang, Ejuan', 'Lu, Mengji', 'Roggendorf, Michael']",Hepat Res Treat,,,True
4bf4126bc494f791347e285c91b25bc2814beb4d,PMC,The Dual Role of TNF in Pulmonary Edema,http://dx.doi.org/10.4103/0975-3583.59983,PMC3004168,21188088,CC BY,"—Pulmonary edema, a major manifestation of left ventricular heart failure, renal insufficiency, shock, diffuse alveolar damage and lung hypersensitivity states, is a significant medical problem worldwide and can be life-threatening. The proinflammatory cytokine tumor necrosis factor (TNF) has been shown to contribute to the pathogenesis and development of pulmonary edema. However, some recent studies have demonstrated surprisingly that TNF can also promote alveolar fluid reabsorption in vivo and in vitro. This protective effect of the cytokine is mediated by the lectin-like domain of the cytokine, which is spatially distinct from the TNF receptor binding sites. The TIP peptide, a synthetic mimic of the lectin-like domain of TNF, can significantly increase alveolar fluid clearance and improve lung compliance in pulmonary edema models. In this review, we will discuss the dual role of TNF in pulmonary edema. ABBREVIATIONS: —tumor necrosis factor (TNF); acute lung injury (ALI); acute respiratory distress syndrome (ARDS); positive end-expiratory pressure (PEEP);epithelial sodium channel (ENaC);neural precursor cell-expressed developmentally downregulated (gene 4) protein (Nedd4-2);serum and glucocorticoid dependent kinase (Sgk-1);insulin-like growth factor 1 (IGF-1);Protein Kinase C (PKC);reactive oxygen species (ROS);myosin light chain (MLC);pneumolysin (PLY);listeriolysin (LLO);interleukin (IL);bronchoalveolar lavage fluids (BALF);Bacillus Calmette-Guerin (BCG);TNF receptor type 1 (TNFR1); TNF receptor type 2 (TNF-R2);",2010 Jan-Mar,"['Yang, Guang', 'Hamacher, Jürg', 'Gorshkov, Boris', 'White, Richard', 'Sridhar, Supriya', 'Verin, Alexander', 'Chakraborty, Trinad', 'Lucas, Rudolf']",J Cardiovasc Dis Res,,,True
91e807f991ce190a25835b2cb4d0ee92ec63545d,PMC,Reconstructed Ancestral Sequences Improve Pathogen Identification Using Resequencing DNA Microarrays,http://dx.doi.org/10.1371/journal.pone.0015243,PMC3004854,21187950,CC BY,"We describe the benefit of using reconstructed ancestral sequences (RAS) on resequencing microarrays for rapid pathogen identification, with Enterobacteriaceae rpoB sequences as a model. Our results demonstrate a sharp improvement of call rate and accuracy when using RASs as compared to extant sequences. This improvement was attributed to the lower sequence divergence of RASs, which also expanded the sequence space covered by the microarray. Extension of this novel microarray design strategy to viruses, antimicrobial resistance elements or toxins is straightforward.",2010 Dec 20,"['Berthet, Nicolas', 'Deletoile, Alexis', 'Passet, Virginie', 'Kennedy, Giulia C.', 'Manuguerra, Jean-Claude', 'Cole, Stewart T.', 'Brisse, Sylvain']",PLoS One,,,True
9adcc3de8f703fe97f002f97da996f4924d5f5ba,PMC,Response to the challenges of pandemic H1N1 in a small island state: the Barbadian experience,http://dx.doi.org/10.1186/1471-2458-10-S1-S10,PMC3005570,21143820,CC BY,"BACKGROUND: Having been overwhelmed by the complexity of the response needed for the severe acute respiratory syndrome (SARS) epidemic, public health professionals in the small island state of Barbados put various measures in place to improve its response in the event of a pandemic METHODS: Data for this study was collected using Barbados’ National Influenza Surveillance System, which was revitalized in 2007. It is comprised of ten sentinel sites which send weekly notifications of acute respiratory illness (ARI) and severe acute respiratory illness (SARI) to the Office of the National Epidemiologist. During the 2009 H1N1 pandemic, meetings of the National Pandemic Planning Committee and the Technical Command Committee were convened. The pharmaceutical and non-pharmaceutical interventions (NPIs) implemented as a result of these meetings form the basis of the results presented in this paper. RESULTS: On June 3, 2009, Barbados reported its first case of 2009 H1N1. From June until October 2009, there were 155 laboratory confirmed cases of 2009 H1N1, with one additional case occurring in January 2010. For the outbreak period (June-October 2009), the surveillance team received reports of 2,483 ARI cases, compared to 412 cases for the same period in 2008. The total hospitalization rate due to SARIs for the year 2009 was 90.1 per 100,000 people, as compared to 7.3 per 100,000 people for 2008. Barbados’ pandemic response was characterized by a strong surveillance system combining active and passive surveillance, good risk communication strategy, a strengthened public and private sector partnership, and effective regional and international collaborations. Community restriction strategies such as school and workplace closures and cancellation of group events were not utilized as public health measures to delay the spread of the virus. Some health care facilities struggled with providing adequate isolation facilities. CONCLUSIONS: The number of confirmed cases was small but the significant surge in ARI and SARI cases indicate that the impact of the virus on the island was moderate. As a result of 2009 H1N1, virological surveillance has improved significantly and local, regional and international partnerships have been strengthened.",2010 Dec 3,"['Sobers-Grannum, Natasha', 'Springer, Karen', 'Ferdinand, Elizabeth', 'John, Joy St']",BMC Public Health,,,True
95e5e02c5d10df5d4559adba6bdf7a834b4d5329,PMC,Global health security and the International Health Regulations,http://dx.doi.org/10.1186/1471-2458-10-S1-S2,PMC3005574,21143824,CC BY,"Global nuclear proliferation, bioterrorism, and emerging infections have challenged national capacities to achieve and maintain global security. Over the last century, emerging infectious disease threats resulted in the development of the preliminary versions of the International Health Regulations (IHR) of the World Health Organization (WHO). The current HR(2005) contain major differences compared to earlier versions, including: substantial shifts from containment at the border to containment at the source of the event; shifts from a rather small disease list (smallpox, plague, cholera, and yellow fever) required to be reported, to all public health threats; and shifts from preset measures to tailored responses with more flexibility to deal with the local situations on the ground. The new IHR(2005) call for accountability. They also call for strengthened national capacity for surveillance and control; prevention, alert, and response to international public health emergencies beyond the traditional short list of required reporting; global partnership and collaboration; and human rights, obligations, accountability, and procedures of monitoring. Under these evolved regulations, as well as other measures, such as the Revolving Fund for vaccine procurement of the Pan American Health Organization (PAHO), global health security could be maintained in the response to urban yellow fever in Paraguay in 2008 and the influenza (H1N1) pandemic of 2009-2010.",2010 Dec 3,"['Andrus, Jon Kim', 'Aguilera, Ximena', 'Oliva, Otavio', 'Aldighieri, Sylvain']",BMC Public Health,,,True
9df9c07c5571ea37b99d01b8ecbfcac5625fa1ef,PMC,Laboratory capacity building for the International Health Regulations (IHR[2005]) in resource-poor countries: the experience of the African Field Epidemiology Network (AFENET),http://dx.doi.org/10.1186/1471-2458-10-S1-S8,PMC3005580,21143830,CC BY,"Laboratory is one of the core capacities that countries must develop for the implementation of the International Health Regulations (IHR[2005]) since laboratory services play a major role in all the key processes of detection, assessment, response, notification, and monitoring of events. While developed countries easily adapt their well-organized routine laboratory services, resource-limited countries need considerable capacity building as many gaps still exist. In this paper, we discuss some of the efforts made by the African Field Epidemiology Network (AFENET) in supporting laboratory capacity development in the Africa region. The efforts range from promoting graduate level training programs to building advanced technical, managerial and leadership skills to in-service short course training for peripheral laboratory staff. A number of specific projects focus on external quality assurance, basic laboratory information systems, strengthening laboratory management towards accreditation, equipment calibration, harmonization of training materials, networking and provision of pre-packaged laboratory kits to support outbreak investigation. Available evidence indicates a positive effect of these efforts on laboratory capacity in the region. However, many opportunities exist, especially to support the roll-out of these projects as well as attending to some additional critical areas such as biosafety and biosecuity. We conclude that AFENET’s approach of strengthening national and sub-national systems provide a model that could be adopted in resource-limited settings such as sub-Saharan Africa.",2010 Dec 3,"['Masanza, Monica Musenero', 'Nqobile, Ndlovu', 'Mukanga, David', 'Gitta, Sheba Nakacubo']",BMC Public Health,,,True
cb0ba244ebf7524d9303edd3c52946f08560f597,PMC,"Assessment of core capacities for the International Health Regulations (IHR[2005]) – Uganda, 2009",http://dx.doi.org/10.1186/1471-2458-10-S1-S9,PMC3005581,21143831,CC BY,"BACKGROUND: Uganda is currently implementing the International Health Regulations (IHR[2005]) within the context of Integrated Disease Surveillance and Response (IDSR). The IHR(2005) require countries to assess the ability of their national structures, capacities, and resources to meet the minimum requirements for surveillance and response. This report describes the results of the assessment undertaken in Uganda. METHODS: We conducted a descriptive cross-sectional assessment using the protocol developed by the World Health Organisation (WHO). The data collection tools were adapted locally and administered to a convenience sample of HR(2005) stakeholders, and frequency analyses were performed. RESULTS: Ugandan national laws relevant to the IHR(2005) existed, but they did not adequately support the full implementation of the IHR(2005). Correspondingly, there was a designated IHR National Focal Point (NFP), but surveillance activities and operational communications were limited to the health sector. All the districts (13/13) had designated disease surveillance offices, most had IDSR technical guidelines (92%, or 12/13), and all (13/13) had case definitions for infectious and zoonotic diseases surveillance. Surveillance guidelines were available at 57% (35/61) of the health facilities, while case definitions were available at 66% (40/61) of the health facilities. The priority diseases list, surveillance guidelines, case definitions and reporting tools were based on the IDSR strategy and hence lacked information on the IHR(2005). The rapid response teams at national and district levels lacked food safety, chemical and radio-nuclear experts. Similarly, there were no guidelines on the outbreak response to food, chemical and radio-nuclear hazards. Comprehensive preparedness plans incorporating IHR(2005) were lacking at national and district levels. A national laboratory policy existed and the strategic plan was being drafted. However, there were critical gaps hampering the efficient functioning of the national laboratory network. Finally, the points of entry for IHR(2005) implementation had not been designated. CONCLUSIONS: The assessment highlighted critical gaps to guide the IHR(2005) planning process. The IHR(2005) action plan should therefore be developed to foster national and international public health security.",2010 Dec 3,"['Wamala, Joseph F', 'Okot, Charles', 'Makumbi, Issa', 'Natseri, Nasan', 'Kisakye, Annet', 'Nanyunja, Miriam', 'Bakamutumaho, Barnabas', 'Lutwama, Julius J', 'Sreedharan, Rajesh', 'Xing, Jun', 'Gaturuku, Peter', 'Aisu, Thomas', 'Da Silveira, Fernando', 'Chungong, Stella']",BMC Public Health,,,True
9b2cf86c30314f63a3aeafcf615dc9a5dee997df,PMC,"Human immunome, bioinformatic analyses using HLA supermotifs and the parasite genome, binding assays, studies of human T cell responses, and immunization of HLA-A*1101 transgenic mice including novel adjuvants provide a foundation for HLA-A03 restricted CD8(+)T cell epitope based, adjuvanted vaccine protective against Toxoplasma gondii",http://dx.doi.org/10.1186/1745-7580-6-12,PMC3009956,21129215,CC BY,"BACKGROUND: Toxoplasmosis causes loss of life, cognitive and motor function, and sight. A vaccine is greatly needed to prevent this disease. The purpose of this study was to use an immmunosense approach to develop a foundation for development of vaccines to protect humans with the HLA-A03 supertype. Three peptides had been identified with high binding scores for HLA-A03 supertypes using bioinformatic algorhythms, high measured binding affinity for HLA-A03 supertype molecules, and ability to elicit IFN-γ production by human HLA-A03 supertype peripheral blood CD8(+ )T cells from seropositive but not seronegative persons. RESULTS: Herein, when these peptides were administered with the universal CD4(+)T cell epitope PADRE (AKFVAAWTLKAAA) and formulated as lipopeptides, or administered with GLA-SE either alone, or with Pam(2)Cys added, we found we successfully created preparations that induced IFN-γ and reduced parasite burden in HLA-A*1101(an HLA-A03 supertype allele) transgenic mice. GLA-SE is a novel emulsified synthetic TLR4 ligand that is known to facilitate development of T Helper 1 cell (TH1) responses. Then, so our peptides would include those expressed in tachyzoites, bradyzoites and sporozoites from both Type I and II parasites, we used our approaches which had identified the initial peptides. We identified additional peptides using bioinformatics, binding affinity assays, and study of responses of HLA-A03 human cells. Lastly, we found that immunization of HLA-A*1101 transgenic mice with all the pooled peptides administered with PADRE, GLA-SE, and Pam(2)Cys is an effective way to elicit IFN-γ producing CD8(+ )splenic T cells and protection. Immunizations included the following peptides together: KSFKDILPK (SAG1(224-232)); AMLTAFFLR (GRA6(164-172)); RSFKDLLKK (GRA7(134-142)); STFWPCLLR (SAG2C(13-21)); SSAYVFSVK((SPA250-258)); and AVVSLLRLLK(SPA(89-98)). This immunization elicited robust protection, measured as reduced parasite burden using a luciferase transfected parasite, luciferin, this novel, HLA transgenic mouse model, and imaging with a Xenogen camera. CONCLUSIONS: Toxoplasma gondii peptides elicit HLA-A03 restricted, IFN-γ producing, CD8(+ )T cells in humans and mice. These peptides administered with adjuvants reduce parasite burden in HLA-A*1101 transgenic mice. This work provides a foundation for immunosense based vaccines. It also defines novel adjuvants for newly identified peptides for vaccines to prevent toxoplasmosis in those with HLA-A03 supertype alleles.",2010 Dec 3,"['Cong, Hua', 'Mui, Ernest J', 'Witola, William H', 'Sidney, John', 'Alexander, Jeff', 'Sette, Alessandro', 'Maewal, Ajesh', 'McLeod, Rima']",Immunome Res,,,True
ac8f8e404ca0e3a052340bf089d90474b38d2b2b,PMC,DC-SIGN (CD209) Promoter −336 A/G Polymorphism Is Associated with Dengue Hemorrhagic Fever and Correlated to DC-SIGN Expression and Immune Augmentation,http://dx.doi.org/10.1371/journal.pntd.0000934,PMC3014977,21245921,CC BY,"BACKGROUND: The C-type lectin DC-SIGN (CD209) is known to be the major dengue receptor on human dendritic cells, and a single nucleotide polymorphism (SNP) in the promoter region of CD209 (−336 A/G; rs4804803) is susceptible to many infectious diseases. We reason that variations in the DC-SIGN gene might have a broad influence on viral replication and host immune responses. METHODS AND FINDINGS: We studied whether the rs4804803 SNP was associated with a susceptibility to dengue fever (DF) and/or dengue hemorrhagic fever (DHF) through genotyping analysis in a Taiwanese cohort. We generated monocyte-derived dendritic cells (MDDCs) from individuals with AA or AG genotype of rs4804803 to study the viral replication and immune responses for functional validation. A total of 574 DNA samples were genotyped, including 176 DF, 135 DHF, 143 other non-dengue febrile illnesses (OFI) and 120 population controls. A strong association between GG/AG genotypes of rs4804803 and risk of DHF was found when compared among DF, OFI and controls (p = 0.004, 3×10(−5) and 0.001, respectively). The AA genotype was associated with protection against dengue infection compared with OFI and controls (p = 0.002 and 0.020, respectively). Moreover, MDDCs from individuals with AG genotype with a higher cell surface DC-SIGN expression had a significantly higher TNFα, IL-12p40, and IP-10 production than those with AA genotype in response to dengue infection. However, the viral replication in MDDCs with AG genotype was significantly lower than those with AA genotype. With both genotypes, MDDCs revealed an increase in viral replication following the addition of anti-IP-10 neutralizing antibody. CONCLUSIONS/SIGNIFICANCE: The rs4804803 SNP in the CD209 promoter contributed to susceptibility to dengue infection and complication of DHF. This SNP with AG genotype affects the cell surface DC-SIGN expression related to immune augmentation and less viral replication.",2011 Jan 4,"['Wang, Lin', 'Chen, Rong-Fu', 'Liu, Jien-Wei', 'Lee, Ing-Kit', 'Lee, Chiu-Ping', 'Kuo, Ho-Chang', 'Huang, Shau-Ku', 'Yang, Kuender D.']",PLoS Negl Trop Dis,,,True
b936109e0b0de2cb59b2ed271614bb710e8e04af,PMC,Thermal Image Scanning for Influenza Border Screening: Results of an Airport Screening Study,http://dx.doi.org/10.1371/journal.pone.0014490,PMC3016318,21245928,CC BY,"BACKGROUND: Infrared thermal image scanners (ITIS) appear an attractive option for the mass screening of travellers for influenza, but there are no published data on their performance in airports. METHODS: ITIS was used to measure cutaneous temperature in 1275 airline travellers who had agreed to tympanic temperature measurement and respiratory sampling. The prediction by ITIS of tympanic temperature (37.8°C and 37.5°C) and of influenza infection was assessed using Receiver Operating Characteristic (ROC) curves and estimated sensitivity, specificity and positive predictive value (PPV). FINDINGS: Using front of face ITIS for prediction of tympanic temperature ≥37.8°C, the area under the ROC curve was 0.86 (95%CI 0.75–0.97) and setting sensitivity at 86% gave specificity of 71%. The PPV in this population of travellers, of whom 0.5% were febrile using this definition, was 1.5%. We identified influenza virus infection in 30 travellers (3 Type A and 27 Type B). For ITIS prediction of influenza infection the area under the ROC curve was 0.66 (0.56–0.75), a sensitivity of 87% gave specificity of 39%, and PPV of 2.8%. None of the 30 influenza-positive travellers had tympanic temperature ≥37.8°C at screening (95%CI 0% to 12%); three had no influenza symptoms. CONCLUSION: ITIS performed moderately well in detecting fever but in this study, during a seasonal epidemic of predominantly influenza type B, the proportion of influenza-infected travellers who were febrile was low and ITIS were not much better than chance at identifying travellers likely to be influenza-infected. Although febrile illness is more common in influenza A infections than influenza B infections, many influenza A infections are afebrile. Our findings therefore suggest that ITIS is unlikely to be effective for entry screening of travellers to detect influenza infection with the intention of preventing entry of the virus into a country.",2011 Jan 5,"['Priest, Patricia C.', 'Duncan, Alasdair R.', 'Jennings, Lance C.', 'Baker, Michael G.']",PLoS One,,,True
39eadd11ec6d5021711bcfa21f0cb6e183242c71,PMC,"Distinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virus",http://dx.doi.org/10.1371/journal.ppat.1001258,PMC3017121,21253575,CC0,"Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV) hemagglutinin (HA) protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP(1,2)) of Marburg and Ebola filoviruses (MARV, EBOV). Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV) and entry mediated by the SARS-CoV spike (S) protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.",2011 Jan 6,"['Huang, I-Chueh', 'Bailey, Charles C.', 'Weyer, Jessica L.', 'Radoshitzky, Sheli R.', 'Becker, Michelle M.', 'Chiang, Jessica J.', 'Brass, Abraham L.', 'Ahmed, Asim A.', 'Chi, Xiaoli', 'Dong, Lian', 'Longobardi, Lindsay E.', 'Boltz, Dutch', 'Kuhn, Jens H.', 'Elledge, Stephen J.', 'Bavari, Sina', 'Denison, Mark R.', 'Choe, Hyeryun', 'Farzan, Michael']",PLoS Pathog,,,True
96b070fe442137ec80f7736790ad13105c549dfd,PMC,A microbial detection array (MDA) for viral and bacterial detection,http://dx.doi.org/10.1186/1471-2164-11-668,PMC3017867,21108826,CC BY,"BACKGROUND: Identifying the bacteria and viruses present in a complex sample is useful in disease diagnostics, product safety, environmental characterization, and research. Array-based methods have proven utility to detect in a single assay at a reasonable cost any microbe from the thousands that have been sequenced. METHODS: We designed a pan-Microbial Detection Array (MDA) to detect all known viruses (including phages), bacteria and plasmids and developed a novel statistical analysis method to identify mixtures of organisms from complex samples hybridized to the array. The array has broader coverage of bacterial and viral targets and is based on more recent sequence data and more probes per target than other microbial detection/discovery arrays in the literature. Family-specific probes were selected for all sequenced viral and bacterial complete genomes, segments, and plasmids. Probes were designed to tolerate some sequence variation to enable detection of divergent species with homology to sequenced organisms, and to have no significant matches to the human genome sequence. RESULTS: In blinded testing on spiked samples with single or multiple viruses, the MDA was able to correctly identify species or strains. In clinical fecal, serum, and respiratory samples, the MDA was able to detect and characterize multiple viruses, phage, and bacteria in a sample to the family and species level, as confirmed by PCR. CONCLUSIONS: The MDA can be used to identify the suite of viruses and bacteria present in complex samples.",2010 Nov 25,"['Gardner, Shea N', 'Jaing, Crystal J', 'McLoughlin, Kevin S', 'Slezak, Tom R']",BMC Genomics,,,True
2032190765972c590630a370d6d2f088270ee9db,PMC,Proteins with RNA Chaperone Activity: A World of Diverse Proteins with a Common Task—Impediment of RNA Misfolding,http://dx.doi.org/10.1155/2011/532908,PMC3017892,21234377,CC BY,"Proteins with RNA chaperone activity are ubiquitous proteins that play important roles in cellular mechanisms. They prevent RNA from misfolding by loosening misfolded structures without ATP consumption. RNA chaperone activity is studied in vitro and in vivo using oligonucleotide- or ribozyme-based assays. Due to their functional as well as structural diversity, a common chaperoning mechanism or universal motif has not yet been identified. A growing database of proteins with RNA chaperone activity has been established based on evaluation of chaperone activity via the described assays. Although the exact mechanism is not yet understood, it is more and more believed that disordered regions within proteins play an important role. This possible mechanism and which proteins were found to possess RNA chaperone activity are discussed here.",2011 Dec 26,"Semrad, Katharina",Biochem Res Int,,,True
e9b30d08d16832b101208cf26d563cfefd8649bb,PMC,Assortativity and the Probability of Epidemic Extinction: A Case Study of Pandemic Influenza A (H1N1-2009),http://dx.doi.org/10.1155/2011/194507,PMC3017939,21234337,CC BY,"Unlike local transmission of pandemic influenza A (H1N1-2009), which was frequently driven by school children, most cases identified in long-distance intranational and international travelers have been adults. The present study examines the relationship between the probability of temporary extinction and the age-dependent next-generation matrix, focusing on the impact of assortativity. Preferred mixing captures as a good approximation the assortativity of a heterogeneously mixing population. We show that the contribution of a nonmaintenance host (i.e., a host type which cannot sustain transmission on its own) to the risk of a major epidemic is greatly diminished as mixing patterns become more assortative, and in such a scenario, a higher proportion of non-maintenance hosts among index cases elevates the probability of extinction. Despite the presence of various other epidemiological factors that undoubtedly influenced the delay between first importations and the subsequent epidemic, these results suggest that the dominance of adults among imported cases represents one of the possible factors explaining the delays in geographic spread observed during the recent pandemic.",2011 Dec 23,"['Nishiura, Hiroshi', 'Cook, Alex R.', 'Cowling, Benjamin J.']",Interdiscip Perspect Infect Dis,,,True
d6631a0f06bb98c73bfde3c98faf886c8be05522,PMC,"Reporting errors in infectious disease outbreaks, with an application to Pandemic Influenza A/H1N1",http://dx.doi.org/10.1186/1742-5573-7-12,PMC3018365,21159178,CC BY,"BACKGROUND: Effectively responding to infectious disease outbreaks requires a well-informed response. Quantitative methods for analyzing outbreak data and estimating key parameters to characterize the spread of the outbreak, including the reproductive number and the serial interval, often assume that the data collected is complete. In reality reporting delays, undetected cases or lack of sensitive and specific tests to diagnose disease lead to reporting errors in the case counts. Here we provide insight on the impact that such reporting errors might have on the estimation of these key parameters. RESULTS: We show that when the proportion of cases reported is changing through the study period, the estimates of key epidemiological parameters are biased. Using data from the Influenza A/H1N1 outbreak in La Gloria, Mexico, we provide estimates of these parameters, accounting for possible reporting errors, and show that they can be biased by as much as 33%, if reporting issues are not accounted for. CONCLUSIONS: Failure to account for missing data can lead to misleading and inaccurate estimates of epidemic parameters.",2010 Dec 15,"['White, Laura F', 'Pagano, Marcello']",Epidemiol Perspect Innov,,,True
50ed67f9700cce235cfb173d78b22053243c1d38,PMC,Alzheimer's Disease: A Pathogenetic Autoimmune Disorder Caused by Herpes Simplex in a Gene-Dependent Manner,http://dx.doi.org/10.4061/2010/140539,PMC3018626,21234306,CC BY,"Herpes simplex is implicated in Alzheimer's disease and viral infection produces Alzheimer's disease like pathology in mice. The virus expresses proteins containing short contiguous amino acid stretches (5–9aa “vatches” = viralmatches) homologous to APOE4, clusterin, PICALM, and complement receptor 1, and to over 100 other gene products relevant to Alzheimer's disease, which are also homologous to proteins expressed by other pathogens implicated in Alzheimer's disease. Such homology, reiterated at the DNA level, suggests that gene association studies have been tracking infection, as well as identifying key genes, demonstrating a role for pathogens as causative agents. Vatches may interfere with the function of their human counterparts, acting as dummy ligands, decoy receptors, or via interactome interference. They are often immunogenic, and antibodies generated in response to infection may target their human counterparts, producing protein knockdown, or generating autoimmune responses that may kill the neurones in which the human homologue resides, a scenario supported by immune activation in Alzheimer's disease. These data may classify Alzheimer's disease as an autoimmune disorder created by pathogen mimicry of key Alzheimer's disease-related proteins. It may well be prevented by vaccination and regular pathogen detection and elimination, and perhaps stemmed by immunosuppression or antibody adsorption-related therapies.",2010 Dec 29,"Carter, C. J.",Int J Alzheimers Dis,,,True
0c4cea0b243a4aa5920a4861426a3c6bb250cf3c,PMC,"SISEA activities in Pasteur Institute in Nha Trang, Vietnam, during 2008–2009",,PMC3019433,,CC BY,,2011 Jan 10,"['Chien, Bui Trong', 'Mai, Vien Quang', 'Mai, Trinh Thi Xuan', 'Nam, Nguyen Hai', 'Thuy, Ðoan Thi thanh']",BMC Proc,,,False
17a82f57ae67bf99733f4bc5ffa157c9176c85fd,PMC,Epidemiology and viral etiologies of Severe Acute Respiratory Infections (SARI) in the Northern Vietnam,,PMC3019434,,CC BY,,2011 Jan 10,"['Hien, Nguyen Tran', 'Thi Thuong, Nguyen', 'Thiem, Vu Dinh', 'Minh, Nguyen Quang', 'Duong, Tran Nhu']",BMC Proc,,,False
c7e06bcb6281367d876863d5a26813e2ad337301,PMC,Identification of viruses in Acute Lower Respiratory Infections (ALRI) in Lao People's Democratic Republic,,PMC3019503,,CC BY,,2011 Jan 10,"['Sentilhes, Anne-Charlotte', 'Xaysitthideth, Vimatha', 'Rith, Sareth', 'Ongkhamme, Somvay', 'Sisouk, Thongchanh', 'Phonekeo, Darouny', 'Bernatas, Jean-Jacques', 'Deubel, Vincent', 'Buchy, Philippe', 'Brey, Paul', 'Vongphrachanh, Phengta']",BMC Proc,,,False
385c5add434a1ed8a8868fe0c37e63486387b454,PMC,The SARS coronavirus E protein interacts with the PALS1 and alters tight junction formation and epithelial morphogenesis,,PMC3019508,,CC BY,,2011 Jan 10,"['Teoh, Kim-Tat', 'Siu, Yu-Lam', 'Chan, Wing-Lim', 'Schlüter, Marc A', 'Liu, Chia-Jen', 'Malik Peiris, J S', 'Bruzzone, Roberto', 'Margolis, Benjamin', 'Nal, Béatrice']",BMC Proc,,,False
0aef63f4f4c4cb195e71b50d0c6e721aba9f2a81,PMC,Investigation of Antibody-Dependent Enhancement (ADE) of SARS coronavirus infection and its role in pathogenesis of SARS,,PMC3019510,,CC BY,,2011 Jan 10,"['Yip, Ming S', 'Cheung, Chung Y', 'Li, Ping H', 'Bruzzone, Roberto', 'Peiris, JS Malik', 'Jaume, Martial']",BMC Proc,,,True
4b2a69ec1289a04f3a94db719f855631f93f2d54,PMC,Liposome-Coupled Peptides Induce Long-Lived Memory CD8(+) T Cells Without CD4(+) T Cells,http://dx.doi.org/10.1371/journal.pone.0015091,PMC3020143,21264321,CC BY,"CD8(+) T cells provide broad immunity to viruses, because they are able to recognize all types of viral proteins. Therefore, the development of vaccines capable of inducing long-lived memory CD8(+) T cells is desired to prevent diseases, especially those for which no vaccines currently exist. However, in designing CD8(+) T cell vaccines, the role of CD4(+) T cells in the induction and maintenance of memory CD8(+) T cells remains uncertain. In the present study, the necessity or not of CD4(+) T cells in the induction and maintenance of memory CD8(+) T cells was investigated in mice immunized with liposome-coupled CTL epitope peptides. When OVA-derived CTL epitope peptides were chemically coupled to the surfaces of liposomes and inoculated into mice, both primary and secondary CTL responses were successfully induced. The results were further confirmed in CD4(+) T cell-eliminated mice, suggesting that CD4(+) T cells were not required for the generation of memory CD8(+) T cells in the case of immunization with liposome-coupled peptides. Thus, surface-linked liposomal antigens, capable of inducing long-lived memory CD8(+) T cells without the contribution of CD4(+) T cells, might be applicable for the development of vaccines to prevent viral infection, especially for those viruses that evade humoral immunity by varying their surface proteins, such as influenza viruses, HIV, HCV, SARS coronaviruses, and Ebola viruses.",2010 Nov 30,"['Taneichi, Maiko', 'Tanaka, Yuriko', 'Kakiuchi, Terutaka', 'Uchida, Tetsuya']",PLoS One,,,True
80ea83eb20c374075380eadb6df930f2d356ea62,PMC,Engineered Toxins “Zymoxins” Are Activated by the HCV NS3 Protease by Removal of an Inhibitory Protein Domain,http://dx.doi.org/10.1371/journal.pone.0015916,PMC3021518,21264238,CC BY,"The synthesis of inactive enzyme precursors, also known as “zymogens,” serves as a mechanism for regulating the execution of selected catalytic activities in a desirable time and/or site. Zymogens are usually activated by proteolytic cleavage. Many viruses encode proteases that execute key proteolytic steps of the viral life cycle. Here, we describe a proof of concept for a therapeutic approach to fighting viral infections through eradication of virally infected cells exclusively, thus limiting virus production and spread. Using the hepatitis C virus (HCV) as a model, we designed two HCV NS3 protease-activated “zymogenized” chimeric toxins (which we denote “zymoxins”). In these recombinant constructs, the bacterial and plant toxins diphtheria toxin A (DTA) and Ricin A chain (RTA), respectively, were fused to rationally designed inhibitor peptides/domains via an HCV NS3 protease-cleavable linker. The above toxins were then fused to the binding and translocation domains of Pseudomonas exotoxin A in order to enable translocation into the mammalian cells cytoplasm. We show that these toxins exhibit NS3 cleavage dependent increase in enzymatic activity upon NS3 protease cleavage in vitro. Moreover, a higher level of cytotoxicity was observed when zymoxins were applied to NS3 expressing cells or to HCV infected cells, demonstrating a potential therapeutic window. The increase in toxin activity correlated with NS3 protease activity in the treated cells, thus the therapeutic window was larger in cells expressing recombinant NS3 than in HCV infected cells. This suggests that the “zymoxin” approach may be most appropriate for application to life-threatening acute infections where much higher levels of the activating protease would be expected.",2011 Jan 14,"['Shapira, Assaf', 'Gal-Tanamy, Meital', 'Nahary, Limor', 'Litvak-Greenfeld, Dana', 'Zemel, Romy', 'Tur-Kaspa, Ran', 'Benhar, Itai']",PLoS One,,,True
0700c01d64e50ef5ae5943328bd734718cf614f4,PMC,An Analysis on the Detection of Biological Contaminants Aboard Aircraft,http://dx.doi.org/10.1371/journal.pone.0014520,PMC3022008,21264266,CC BY,"The spread of infectious disease via commercial airliner travel is a significant and realistic threat. To shed some light on the feasibility of detecting airborne pathogens, a sensor integration study has been conducted and computational investigations of contaminant transport in an aircraft cabin have been performed. Our study took into consideration sensor sensitivity as well as the time-to-answer, size, weight and the power of best available commercial off-the-shelf (COTS) devices. We conducted computational fluid dynamics simulations to investigate three types of scenarios: (1) nominal breathing (up to 20 breaths per minute) and coughing (20 times per hour); (2) nominal breathing and sneezing (4 times per hour); and (3) nominal breathing only. Each scenario was implemented with one or seven infectious passengers expelling air and sneezes or coughs at the stated frequencies. Scenario 2 was implemented with two additional cases in which one infectious passenger expelled 20 and 50 sneezes per hour, respectively. All computations were based on 90 minutes of sampling using specifications from a COTS aerosol collector and biosensor. Only biosensors that could provide an answer in under 20 minutes without any manual preparation steps were included. The principal finding was that the steady-state bacteria concentrations in aircraft would be high enough to be detected in the case where seven infectious passengers are exhaling under scenarios 1 and 2 and where one infectious passenger is actively exhaling in scenario 2. Breathing alone failed to generate sufficient bacterial particles for detection, and none of the scenarios generated sufficient viral particles for detection to be feasible. These results suggest that more sensitive sensors than the COTS devices currently available and/or sampling of individual passengers would be needed for the detection of bacteria and viruses in aircraft.",2011 Jan 17,"['Hwang, Grace M.', 'DiCarlo, Anthony A.', 'Lin, Gene C.']",PLoS One,,,True
cddc369300f073cb0ba20e276fee32112502f4f7,PMC,Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses,http://dx.doi.org/10.1186/1471-2172-11-65,PMC3023737,21194475,CC BY,"BACKGROUND: Immunization with the spike protein (S) of severe acute respiratory syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K (PEI) is a cationic polymer which effectively delivers the plasmid DNA. RESULTS: In the present study, the immune responses of BALB/c mice immunized via intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form have been examined. The size of the PEI/pci-S nanoparticles appeared to be around 194.7 ± 99.3 nm, and the expression of the S mRNA and protein was confirmed in vitro. The mice immunized with i.n. PEI/pci-S nanoparticles produced significantly (P < 0.05) higher S-specific IgG1 in the sera and mucosal secretory IgA in the lung wash than those in mice treated with pci-S alone. Compared to those in mice challenged with pci-S alone, the number of B220(+ )cells found in PEI/pci-S vaccinated mice was elevated. Co-stimulatory molecules (CD80 and CD86) and class II major histocompatibility complex molecules (I-A(d)) were increased on CD11c(+ )dendritic cells in cervical lymph node from the mice after PEI/pci-S vaccination. The percentage of IFN-γ-, TNF-α- and IL-2-producing cells were higher in PEI/pci-S vaccinated mice than in control mice. CONCLUSION: These results showed that intranasal immunization with PEI/pci-S nanoparticles induce antigen specific humoral and cellular immune responses.",2010 Dec 31,"['Shim, Byoung-Shik', 'Park, Sung-Moo', 'Quan, Ji-Shan', 'Jere, Dhananjay', 'Chu, Hyuk', 'Song, Man Ki', 'Kim, Dong Wook', 'Jang, Yong-Suk', 'Yang, Moon-Sik', 'Han, Seung Hyun', 'Park, Yong-Ho', 'Cho, Chong-Su', 'Yun, Cheol-Heui']",BMC Immunol,,,True
f8abd9e10df6beeffec38bc7dd7083318e0d69ed,PMC,Improvement of different vaccine delivery systems for cancer therapy,http://dx.doi.org/10.1186/1476-4598-10-3,PMC3024302,21211062,CC BY,"Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs) have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs) such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP) have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.",2011 Jan 7,"['Bolhassani, Azam', 'Safaiyan, Shima', 'Rafati, Sima']",Mol Cancer,,,True
1763110ecc1742f6158f410a0c4f0b923118fd79,PMC,The Ras–PI3K Signaling Pathway Is Involved in Clathrin-Independent Endocytosis and the Internalization of Influenza Viruses,http://dx.doi.org/10.1371/journal.pone.0016324,PMC3024431,21283725,CC BY,"BACKGROUND: Influenza virus infection causes highly contagious, severe respiratory disorders and gives rise to thousands of deaths every year; however, the efficacy of currently approved defense strategies, including vaccines and neuraminidase inhibitors, is limited because the virus frequently acquires resistance via antigen drift and reassortment. It is therefore important to establish a novel, effective therapeutic strategy that is effective irrespective of viral subtype. METHODOLOGY/PRINCIPAL FINDINGS: Here, we identify the Ras–phosphoinositide 3-kinase (PI3K) signaling pathway as a host-cell regulatory mechanism for influenza virus entry. The binding of Ras to PI3K is specifically involved in clathrin-independent endocytosis, endosomal maturation, and intracellular transport of viruses, which result in decreased infectious efficacy of different subtypes of influenza viruses in cells lacking the Ras–PI3K interaction. Moreover, influenza virus infection indeed triggered Ras activation and subsequent PI3K activation in early endosomes. CONCLUSIONS/SIGNIFICANCE: Taken together, these results demonstrate that the Ras–PI3K signaling axis acts as a host-oriented mechanism for viral internalization. Given that virus incorporation is a process conserved among virus subtypes and species, this signaling pathway may provide a target for potent, well-tolerated prophylactics and therapeutics against a broad range of viruses.",2011 Jan 20,"['Fujioka, Yoichiro', 'Tsuda, Masumi', 'Hattori, Tomoe', 'Sasaki, Junko', 'Sasaki, Takehiko', 'Miyazaki, Tadaaki', 'Ohba, Yusuke']",PLoS One,,,True
464e498ad4c25f88b02533864c5415900e53e412,PMC,Full-length Ebola glycoprotein accumulates in the endoplasmic reticulum,http://dx.doi.org/10.1186/1743-422X-8-11,PMC3024955,21223600,CC BY,"The Filoviridae family comprises of Ebola and Marburg viruses, which are known to cause lethal hemorrhagic fever. However, there is no effective anti-viral therapy or licensed vaccines currently available for these human pathogens. The envelope glycoprotein (GP) of Ebola virus, which mediates entry into target cells, is cytotoxic and this effect maps to a highly glycosylated mucin-like region in the surface subunit of GP (GP1). However, the mechanism underlying this cytotoxic property of GP is unknown. To gain insight into the basis of this GP-induced cytotoxicity, HEK293T cells were transiently transfected with full-length and mucin-deleted (Δmucin) Ebola GP plasmids and GP localization was examined relative to the nucleus, endoplasmic reticulum (ER), Golgi, early and late endosomes using deconvolution fluorescent microscopy. Full-length Ebola GP was observed to accumulate in the ER. In contrast, GPΔmucin was uniformly expressed throughout the cell and did not localize in the ER. The Ebola major matrix protein VP40 was also co-expressed with GP to investigate its influence on GP localization. GP and VP40 co-expression did not alter GP localization to the ER. Also, when VP40 was co-expressed with the nucleoprotein (NP), it localized to the plasma membrane while NP accumulated in distinct cytoplasmic structures lined with vimentin. These latter structures are consistent with aggresomes and may serve as assembly sites for filoviral nucleocapsids. Collectively, these data suggest that full-length GP, but not GPΔmucin, accumulates in the ER in close proximity to the nuclear membrane, which may underscore its cytotoxic property.",2011 Jan 12,"['Bhattacharyya, Suchita', 'Hope, Thomas J']",Virol J,,,True
820f3633db1b3b98889e6a0d257d10d385be85c8,PMC,Prime immunization with rotavirus VLP 2/6 followed by boosting with an adenovirus expressing VP6 induces protective immunization against rotavirus in mice,http://dx.doi.org/10.1186/1743-422X-8-3,PMC3024956,21205330,CC BY,"BACKGROUND: Rotavirus (RV) is the main cause of severe gastroenteritis in children. An effective vaccination regime against RV can substantially reduce morbidity and mortality. Previous studies have demonstrated the efficacy of virus-like particles formed by RV VP2 and VP6 (VLP2/6), as well as that of recombinant adenovirus expressing RV VP6 (rAd), in eliciting protective immunities against RV. However, the efficacy of such prime-boost strategy, which incorporates VLP and rAd in inducing protective immunities against RV, has not been addressed. We assessed the immune effects of different regimens in mice, including rAd prime-VLP2/6 boost (rAd+VLP), VLP2/6 prime-rAd boost (VLP+rAd), rAd alone, and VLP alone. RESULTS: Mice immunized with the VLP+rAd regimen elicit stronger humoral, mucosal, and cellular immune responses than those immunized with other regimens. RV challenging experiments showed that the highest reduction (92.9%) in viral shedding was achieved in the VLP+rAd group when compared with rAd+VLP (25%), VLP alone (75%), or rAd alone (40%) treatment groups. The reduction in RV shedding in mice correlated with fecal IgG (r = 0.95773, P = 0.04227) and IgA (r = 0.96137, P = 0.038663). CONCLUSIONS: A VLP2/6 prime-rAd boost regimen is effective in conferring immunoprotection against RV challenge in mice. This finding may lay the groundwork for an alternative strategy in novel RV vaccine development.",2011 Jan 5,"['Zhou, Hongli', 'Guo, Li', 'Wang, Min', 'Qu, Jianguo', 'Zhao, Zhendong', 'Wang, Jianwei', 'Hung, Tao']",Virol J,,,True
7941d4720a1cb228b2380a42885532440f5b7a0a,PMC,A Sensitive Assay for Virus Discovery in Respiratory Clinical Samples,http://dx.doi.org/10.1371/journal.pone.0016118,PMC3025933,21283679,CC BY,"In 5–40% of respiratory infections in children, the diagnostics remain negative, suggesting that the patients might be infected with a yet unknown pathogen. Virus discovery cDNA-AFLP (VIDISCA) is a virus discovery method based on recognition of restriction enzyme cleavage sites, ligation of adaptors and subsequent amplification by PCR. However, direct discovery of unknown pathogens in nasopharyngeal swabs is difficult due to the high concentration of ribosomal RNA (rRNA) that acts as competitor. In the current study we optimized VIDISCA by adjusting the reverse transcription enzymes and decreasing rRNA amplification in the reverse transcription, using hexamer oligonucleotides that do not anneal to rRNA. Residual cDNA synthesis on rRNA templates was further reduced with oligonucleotides that anneal to rRNA but can not be extended due to 3′-dideoxy-C6-modification. With these modifications >90% reduction of rRNA amplification was established. Further improvement of the VIDISCA sensitivity was obtained by high throughput sequencing (VIDISCA-454). Eighteen nasopharyngeal swabs were analysed, all containing known respiratory viruses. We could identify the proper virus in the majority of samples tested (11/18). The median load in the VIDISCA-454 positive samples was 7.2 E5 viral genome copies/ml (ranging from 1.4 E3–7.7 E6). Our results show that optimization of VIDISCA and subsequent high-throughput-sequencing enhances sensitivity drastically and provides the opportunity to perform virus discovery directly in patient material.",2011 Jan 24,"['de Vries, Michel', 'Deijs, Martin', 'Canuti, Marta', 'van Schaik, Barbera D. C.', 'Faria, Nuno R.', 'van de Garde, Martijn D. B.', 'Jachimowski, Loes C. M.', 'Jebbink, Maarten F.', 'Jakobs, Marja', 'Luyf, Angela C. M.', 'Coenjaerts, Frank E. J.', 'Claas, Eric C. J.', 'Molenkamp, Richard', 'Koekkoek, Sylvie M.', 'Lammens, Christine', 'Leus, Frank', 'Goossens, Herman', 'Ieven, Margareta', 'Baas, Frank', 'van der Hoek, Lia']",PLoS One,,,True
8ba5919b2b4c229c9c1685852cf19a1d727ac220,PMC,Assessment of Virally Vectored Autoimmunity as a Biocontrol Strategy for Cane Toads,http://dx.doi.org/10.1371/journal.pone.0014576,PMC3026784,21283623,CC0,"BACKGROUND: The cane toad, Bufo (Chaunus) marinus, is one of the most notorious vertebrate pests introduced into Australia over the last 200 years and, so far, efforts to identify a naturally occurring B. marinus-specific pathogen for use as a biological control agent have been unsuccessful. We explored an alternative approach that entailed genetically modifying a pathogen with broad host specificity so that it no longer caused disease, but carried a gene to disrupt the cane toad life cycle in a species specific manner. METHODOLOGY/PRINCIPAL FINDINGS: The adult beta globin gene was selected as the model gene for proof of concept of autoimmunity as a biocontrol method for cane toads. A previous report showed injection of bullfrog tadpoles with adult beta globin resulted in an alteration in the form of beta globin expressed in metamorphs as well as reduced survival. In B. marinus we established for the first time that the switch from tadpole to adult globin exists. The effect of injecting B. marinus tadpoles with purified recombinant adult globin protein was then assessed using behavioural (swim speed in tadpoles and jump length in metamorphs), developmental (time to metamorphosis, weight and length at various developmental stages, protein profile of adult globin) and genetic (adult globin mRNA levels) measures. However, we were unable to detect any differences between treated and control animals. Further, globin delivery using Bohle iridovirus, an Australian ranavirus isolate belonging to the Iridovirus family, did not reduce the survival of metamorphs or alter the form of beta globin expressed in metamorphs. CONCLUSIONS/SIGNIFICANCE: While we were able to show for the first time that the switch from tadpole to adult globin does occur in B. marinus, we were not able to induce autoimmunity and disrupt metamorphosis. The short development time of B. marinus tadpoles may preclude this approach.",2011 Jan 25,"['Pallister, Jackie A.', 'Halliday, Damien C.T.', 'Robinson, Anthony J.', 'Venables, Daryl', 'Voysey, Rhonda D.', 'Boyle, Donna G.', 'Shanmuganathan, Thayalini', 'Hardy, Christopher M.', 'Siddon, Nicole A.', 'Hyatt, Alex D.']",PLoS One,,,True
bb89ed5e7ed332cbc8565262db8a04d55e2869ef,PMC,Mechanism of Inhibition of Enveloped Virus Membrane Fusion by the Antiviral Drug Arbidol,http://dx.doi.org/10.1371/journal.pone.0015874,PMC3026800,21283579,CC BY,"The broad-spectrum antiviral arbidol (Arb) inhibits cell entry of enveloped viruses by blocking viral fusion with host cell membrane. To better understand Arb mechanism of action, we investigated its interactions with phospholipids and membrane peptides. We demonstrate that Arb associates with phospholipids in the micromolar range. NMR reveals that Arb interacts with the polar head-group of phospholipid at the membrane interface. Fluorescence studies of interactions between Arb and either tryptophan derivatives or membrane peptides reconstituted into liposomes show that Arb interacts with tryptophan in the micromolar range. Interestingly, apparent binding affinities between lipids and tryptophan residues are comparable with those of Arb IC50 of the hepatitis C virus (HCV) membrane fusion. Since tryptophan residues of membrane proteins are known to bind preferentially at the membrane interface, these data suggest that Arb could increase the strength of virus glycoprotein's interactions with the membrane, due to a dual binding mode involving aromatic residues and phospholipids. The resulting complexation would inhibit the expected viral glycoprotein conformational changes required during the fusion process. Our findings pave the way towards the design of new drugs exhibiting Arb-like interfacial membrane binding properties to inhibit early steps of virus entry, i.e., attractive targets to combat viral infection.",2011 Jan 25,"['Teissier, Elodie', 'Zandomeneghi, Giorgia', 'Loquet, Antoine', 'Lavillette, Dimitri', 'Lavergne, Jean-Pierre', 'Montserret, Roland', 'Cosset, François-Loïc', 'Böckmann, Anja', 'Meier, Beat H.', 'Penin, François', 'Pécheur, Eve-Isabelle']",PLoS One,,,True
1546fd2f004f233eea33c99a54f863ee80ffedaf,PMC,Evaluation of an Adjustable Epidemiologic Information System,http://dx.doi.org/10.1371/journal.pone.0014596,PMC3029279,21298043,CC BY,"BACKGROUND: In order to facilitate public health response and to achieve early control of infectious disease epidemics, an adjustable epidemiologic information system (AEIS) was established in the Taiwan public health network in February 2006. METHODOLOGY/PRINCIPAL FINDINGS: The performance of AEIS for the period 2006 through 2008 was evaluated based on a number of response times (RT) and the public health impact. After implementation of the system, the apparent overall shortened RT was mainly due to the shortening of personnel response time (PRT) and the time needed to draft a new questionnaire that incurred as personnel-system interface (PSI); PRT dropped from a fluctuating range of 9.8 ∼28.8 days in the first four months to <10 days in the following months and remained low till 2008 (0.88±1.52 days). The PSIs for newly emerged infectious diseases were 2.6 and 3.4 person-hours for H5N1 in 2007 and chikungunya in 2008, respectively, a much improvement from 1142.5 person-hours for SARS in 2003. The duration of each rubella epidemic cluster was evaluated as public health impact and showed a shortening trend (p = 0.019) that concurred with the shortening of PRT from 64.8±47.3 to 25.2±38.2 hours per cluster (p<0.0001). CONCLUSIONS/SIGNIFICANCE: The first evaluation of the novel instrument AEIS that had been used to assist Taiwan's multi-level government for infectious diseases control demonstrated that it was well integrated into the existing public health infrastructure. It provided flexible tools and computer algorithms with friendly interface for timely data collection, integration, and analysis; as a result, it shortened RTs, filled in gaps of personnel lacking sufficient experiences, created a more efficient flow of response, and identified asymptomatic/mild cases early to minimize further spreading. With further development, AEIS is anticipated to be useful in the application of other acute public health events needing immediate orchestrated data collection and public health actions.",2011 Jan 27,"['Wu, Jiunn-Shyan Julian', 'Shih, Fu-Yuan', 'Chiu, Chan-Hsien', 'Yeh, Yuan-Lih', 'Yan, Jer-Jea', 'King, Chwan-Chuen', 'Ho, Mei-Shang']",PLoS One,,,True
c8eebd3a71f902afe3e21142b9ea8b4f7bf60018,PMC,Evaluation of an Adjustable Epidemiologic Information System,http://dx.doi.org/10.1371/journal.pone.0014596,PMC3029279,21298043,CC BY,"BACKGROUND: In order to facilitate public health response and to achieve early control of infectious disease epidemics, an adjustable epidemiologic information system (AEIS) was established in the Taiwan public health network in February 2006. METHODOLOGY/PRINCIPAL FINDINGS: The performance of AEIS for the period 2006 through 2008 was evaluated based on a number of response times (RT) and the public health impact. After implementation of the system, the apparent overall shortened RT was mainly due to the shortening of personnel response time (PRT) and the time needed to draft a new questionnaire that incurred as personnel-system interface (PSI); PRT dropped from a fluctuating range of 9.8 ∼28.8 days in the first four months to <10 days in the following months and remained low till 2008 (0.88±1.52 days). The PSIs for newly emerged infectious diseases were 2.6 and 3.4 person-hours for H5N1 in 2007 and chikungunya in 2008, respectively, a much improvement from 1142.5 person-hours for SARS in 2003. The duration of each rubella epidemic cluster was evaluated as public health impact and showed a shortening trend (p = 0.019) that concurred with the shortening of PRT from 64.8±47.3 to 25.2±38.2 hours per cluster (p<0.0001). CONCLUSIONS/SIGNIFICANCE: The first evaluation of the novel instrument AEIS that had been used to assist Taiwan's multi-level government for infectious diseases control demonstrated that it was well integrated into the existing public health infrastructure. It provided flexible tools and computer algorithms with friendly interface for timely data collection, integration, and analysis; as a result, it shortened RTs, filled in gaps of personnel lacking sufficient experiences, created a more efficient flow of response, and identified asymptomatic/mild cases early to minimize further spreading. With further development, AEIS is anticipated to be useful in the application of other acute public health events needing immediate orchestrated data collection and public health actions.",2011 Jan 27,"['Wu, Jiunn-Shyan Julian', 'Shih, Fu-Yuan', 'Chiu, Chan-Hsien', 'Yeh, Yuan-Lih', 'Yan, Jer-Jea', 'King, Chwan-Chuen', 'Ho, Mei-Shang']",PLoS One,,,False
61e9b0e59092872671011d724f22401d3c2f8288,PMC,A Recombinant Vaccine of H5N1 HA1 Fused with Foldon and Human IgG Fc Induced Complete Cross-Clade Protection against Divergent H5N1 Viruses,http://dx.doi.org/10.1371/journal.pone.0016555,PMC3029370,21304591,CC BY,"Development of effective vaccines to prevent influenza, particularly highly pathogenic avian influenza (HPAI) caused by influenza A virus (IAV) subtype H5N1, is a challenging goal. In this study, we designed and constructed two recombinant influenza vaccine candidates by fusing hemagglutinin 1 (HA1) fragment of A/Anhui/1/2005(H5N1) to either Fc of human IgG (HA1-Fc) or foldon plus Fc (HA1-Fdc), and evaluated their immune responses and cross-protection against divergent strains of H5N1 virus. Results showed that these two recombinant vaccines induced strong immune responses in the vaccinated mice, which specifically reacted with HA1 proteins and an inactivated heterologous H5N1 virus. Both proteins were able to cross-neutralize infections by one homologous strain (clade 2.3) and four heterologous strains belonging to clades 0, 1, and 2.2 of H5N1 pseudoviruses as well as three heterologous strains (clades 0, 1, and 2.3.4) of H5N1 live virus. Importantly, immunization with these two vaccine candidates, especially HA1-Fdc, provided complete cross-clade protection against high-dose lethal challenge of different strains of H5N1 virus covering clade 0, 1, and 2.3.4 in the tested mouse model. This study suggests that the recombinant fusion proteins, particularly HA1-Fdc, could be developed into an efficacious universal H5N1 influenza vaccine, providing cross-protection against infections by divergent strains of highly pathogenic H5N1 virus.",2011 Jan 27,"['Du, Lanying', 'Leung, Virtual Ho-Chuen', 'Zhang, Xiujuan', 'Zhou, Jie', 'Chen, Min', 'He, Wu', 'Zhang, Hai-Ying', 'Chan, Chris C. S.', 'Poon, Vincent Kwok-Man', 'Zhao, Guangyu', 'Sun, Shihui', 'Cai, Lifeng', 'Zhou, Yusen', 'Zheng, Bo-Jian', 'Jiang, Shibo']",PLoS One,,,True
6b5de60d9f674c951315c0c7549fe9e9987e239f,PMC,"Adenovirus serotype 7 associated with a severe lower respiratory tract disease outbreak in infants in Shaanxi Province, China",http://dx.doi.org/10.1186/1743-422X-8-23,PMC3030507,21241515,CC BY,"BACKGROUND: Pneumonia caused by adenovirus infection is usually severe especially with adenovirus serotype 7 commonly associated with lower respiratory tract disease outbreaks. We reported an outbreak of 70 cases of severe pneumonia with one death of infants in Shaanxi Province, China. Sampling showed adenovirus 7 (Ad7) as the primary pathogen with some co-infections. RESULTS: Two strains of adenovirus and two strains of enterovirus were isolated, the 21 pharynx swabs showed 14 positive amplifications for adenovirus; three co-infections with respiratory syncytial virus, two positive for rhinovirus, one positive for parainfluenza 3, and four negative. Adenovirus typing showed nine of the nine adenovirus positive samples were HAdV-7, three were HAdV-3 and two were too weak to perform sequencing. The entire hexon gene of adenovirus was sequenced and analyzed for the two adenovirus serotype 7 isolates, showing the nucleic acid homology was 99.8% between the two strains and 99.5% compared to the reference strain HAdV-7 (GenBank accession number AY769946). For the 21 acute phase serum samples from the 21 patients, six samples had positives results for ELISA detection of HAdV IgA, and the neutralization titers of the convalescent-phase samples were four times higher than those of the acute-phase samples in nine pairs. CONCLUSIONS: We concluded adenovirus was the viral pathogen, primarily HAdV-7, with some co-infections responsible for the outbreak. This is the first report of an infant pneumonia outbreak caused by adenovirus serotype 7 in Shaanxi Province, China.",2011 Jan 18,"['Tang, Liuying', 'Wang, Li', 'Tan, Xiaojuan', 'Xu, Wenbo']",Virol J,,,True
5206b0be1000e6c8d75a827af94c1b8e61e297c3,PMC,Travel Patterns in China,http://dx.doi.org/10.1371/journal.pone.0016364,PMC3032737,21311745,CC BY,"The spread of infectious disease epidemics is mediated by human travel. Yet human mobility patterns vary substantially between countries and regions. Quantifying the frequency of travel and length of journeys in well-defined population is therefore critical for predicting the likely speed and pattern of spread of emerging infectious diseases, such as a new influenza pandemic. Here we present the results of a large population survey undertaken in 2007 in two areas of China: Shenzhen city in Guangdong province, and Huangshan city in Anhui province. In each area, 10,000 randomly selected individuals were interviewed, and data on regular and occasional journeys collected. Travel behaviour was examined as a function of age, sex, economic status and home location. Women and children were generally found to travel shorter distances than men. Travel patterns in the economically developed Shenzhen region are shown to resemble those in developed and economically advanced middle income countries with a significant fraction of the population commuting over distances in excess of 50 km. Conversely, in the less developed rural region of Anhui, travel was much more local, with very few journeys over 30 km. Travel patterns in both populations were well-fitted by a gravity model with a lognormal kernel function. The results provide the first quantitative information on human travel patterns in modern China, and suggest that a pandemic emerging in a less developed area of rural China might spread geographically sufficiently slowly for containment to be feasible, while spatial spread in the more economically developed areas might be expected to be much more rapid, making containment more difficult.",2011 Feb 2,"['Garske, Tini', 'Yu, Hongjie', 'Peng, Zhibin', 'Ye, Min', 'Zhou, Hang', 'Cheng, Xiaowen', 'Wu, Jiabing', 'Ferguson, Neil']",PLoS One,,,True
ca0f03f52fc023762577857285184f9777dc9a27,PMC,Travel Patterns in China,http://dx.doi.org/10.1371/journal.pone.0016364,PMC3032737,21311745,CC BY,"The spread of infectious disease epidemics is mediated by human travel. Yet human mobility patterns vary substantially between countries and regions. Quantifying the frequency of travel and length of journeys in well-defined population is therefore critical for predicting the likely speed and pattern of spread of emerging infectious diseases, such as a new influenza pandemic. Here we present the results of a large population survey undertaken in 2007 in two areas of China: Shenzhen city in Guangdong province, and Huangshan city in Anhui province. In each area, 10,000 randomly selected individuals were interviewed, and data on regular and occasional journeys collected. Travel behaviour was examined as a function of age, sex, economic status and home location. Women and children were generally found to travel shorter distances than men. Travel patterns in the economically developed Shenzhen region are shown to resemble those in developed and economically advanced middle income countries with a significant fraction of the population commuting over distances in excess of 50 km. Conversely, in the less developed rural region of Anhui, travel was much more local, with very few journeys over 30 km. Travel patterns in both populations were well-fitted by a gravity model with a lognormal kernel function. The results provide the first quantitative information on human travel patterns in modern China, and suggest that a pandemic emerging in a less developed area of rural China might spread geographically sufficiently slowly for containment to be feasible, while spatial spread in the more economically developed areas might be expected to be much more rapid, making containment more difficult.",2011 Feb 2,"['Garske, Tini', 'Yu, Hongjie', 'Peng, Zhibin', 'Ye, Min', 'Zhou, Hang', 'Cheng, Xiaowen', 'Wu, Jiabing', 'Ferguson, Neil']",PLoS One,,,True
4ec2396b81441bf6b11b19a271cbc96078a8f3ce,PMC,Travel Patterns in China,http://dx.doi.org/10.1371/journal.pone.0016364,PMC3032737,21311745,CC BY,"The spread of infectious disease epidemics is mediated by human travel. Yet human mobility patterns vary substantially between countries and regions. Quantifying the frequency of travel and length of journeys in well-defined population is therefore critical for predicting the likely speed and pattern of spread of emerging infectious diseases, such as a new influenza pandemic. Here we present the results of a large population survey undertaken in 2007 in two areas of China: Shenzhen city in Guangdong province, and Huangshan city in Anhui province. In each area, 10,000 randomly selected individuals were interviewed, and data on regular and occasional journeys collected. Travel behaviour was examined as a function of age, sex, economic status and home location. Women and children were generally found to travel shorter distances than men. Travel patterns in the economically developed Shenzhen region are shown to resemble those in developed and economically advanced middle income countries with a significant fraction of the population commuting over distances in excess of 50 km. Conversely, in the less developed rural region of Anhui, travel was much more local, with very few journeys over 30 km. Travel patterns in both populations were well-fitted by a gravity model with a lognormal kernel function. The results provide the first quantitative information on human travel patterns in modern China, and suggest that a pandemic emerging in a less developed area of rural China might spread geographically sufficiently slowly for containment to be feasible, while spatial spread in the more economically developed areas might be expected to be much more rapid, making containment more difficult.",2011 Feb 2,"['Garske, Tini', 'Yu, Hongjie', 'Peng, Zhibin', 'Ye, Min', 'Zhou, Hang', 'Cheng, Xiaowen', 'Wu, Jiabing', 'Ferguson, Neil']",PLoS One,,,True
373811bcfe3a46dc6d49b2a1725f1dde8a59e8a9,PMC,"Spatial dynamics of the 1918 influenza pandemic in England, Wales and the United States",http://dx.doi.org/10.1098/rsif.2010.0216,PMC3033019,20573630,CC BY,"There is still limited understanding of key determinants of spatial spread of influenza. The 1918 pandemic provides an opportunity to elucidate spatial determinants of spread on a large scale. To better characterize the spread of the 1918 major wave, we fitted a range of city-to-city transmission models to mortality data collected for 246 population centres in England and Wales and 47 cities in the US. Using a gravity model for city-to-city contacts, we explored the effect of population size and distance on the spread of disease and tested assumptions regarding density dependence in connectivity between cities. We employed Bayesian Markov Chain Monte Carlo methods to estimate parameters of the model for population, infectivity, distance and density dependence. We inferred the most likely transmission trees for both countries. For England and Wales, a model that estimated the degree of density dependence in connectivity between cities was preferable by deviance information criterion comparison. Early in the major wave, long distance infective interactions predominated, with local infection events more likely as the epidemic became widespread. For the US, with fewer more widely dispersed cities, statistical power was lacking to estimate population size dependence or the degree of density dependence, with the preferred model depending on distance only. We find that parameters estimated from the England and Wales dataset can be applied to the US data with no likelihood penalty.",2011 Feb 6,"['Eggo, Rosalind M.', 'Cauchemez, Simon', 'Ferguson, Neil M.']",J R Soc Interface,,,True
cf85ce2e8400011f5119b0eb1a87ffb7933b84a1,PMC,Contribution of complement activation pathways to neuropathology differs among mouse models of Alzheimer's disease,http://dx.doi.org/10.1186/1742-2094-8-4,PMC3033336,21235806,CC BY,"BACKGROUND: Complement proteins and activation products have been found associated with neuropathology in Alzheimer's disease (AD). Recently, a C5a receptor antagonist was shown to suppress neuropathology in two murine models of AD, Tg2576 and 3xTg. Previously, a genetic deficiency of C1q in the Tg2576 mouse model showed an accumulation of fibrillar plaques similar to the complement sufficient Tg2576, but reactive glia were significantly decreased and neuronal integrity was improved suggesting detrimental consequences for complement activation in AD. The goal of this study was to define the role of the classical complement activation pathway in the progression of pathology in the 3xTg mouse that develops tangles in addition to fibrillar plaques (more closely reflecting human AD pathology) and to assess the influence of complement in a model of AD with a higher level of complement hemolytic activity. METHODS: 3xTg mice deficient in C1q (3xTgQ-/-) were generated, and both 3xTg and 3xTgQ-/- were backcrossed to the BUB mouse strain which has higher in vitro hemolytic complement activity. Mice were aged and perfused, and brain sections stained for pathological markers or analyzed for proinflammatory marker expression. RESULTS: 3xTgQ-/- mice showed similar amounts of fibrillar amyloid, reactive glia and hyperphosphorylated tau as the C1q-sufficient 3xTg at the ages analyzed. However, 3xTg and 3xTgQ-/- on the BUB background developed pathology earlier than on the original 3xTg background, although the presence of C1q had no effect on neuropathological and pro-inflammatory markers. In contrast to that seen in other transgenic models of AD, C1q, C4 and C3 immunoreactivity was undetectable on the plaques of 3xTg in any background, although C3 was associated with reactive astrocytes surrounding the plaques. Importantly, properdin a component of the alternative complement pathway was associated with plaques in all models. CONCLUSIONS: In contrast to previously investigated transgenic models of AD, development of neuropathology in 3xTg mice, which progresses much slower than other murine models, may not be influenced by fibrillar amyloid mediated activation of the classical complement pathway, suggesting that the alternative complement pathway activation or a C3-independent cleavage of C5 could account for the detrimental effects in these mice that are prevented by the C5a receptor antagonist. Furthermore, the paucity of complement activation may be a factor in the slower kinetics of progression of pathology in the 3xTg model of this disease.",2011 Jan 15,"['Fonseca, Maria I', 'Chu, Shu-Hui', 'Berci, Alisia M', 'Benoit, Marie E', 'Peters, Douglas G', 'Kimura, Yuko', 'Tenner, Andrea J']",J Neuroinflammation,,,True
b708da1945a7a42cd61526e043d527592d4d9518,PMC,Charge-Surrounded Pockets and Electrostatic Interactions with Small Ions Modulate the Activity of Retroviral Fusion Proteins,http://dx.doi.org/10.1371/journal.ppat.1001268,PMC3033372,21304939,CC BY,"Refolding of viral class-1 membrane fusion proteins from a native state to a trimer-of-hairpins structure promotes entry of viruses into cells. Here we present the structure of the bovine leukaemia virus transmembrane glycoprotein (TM) and identify a group of asparagine residues at the membrane-distal end of the trimer-of-hairpins that is strikingly conserved among divergent viruses. These asparagines are not essential for surface display of pre-fusogenic envelope. Instead, substitution of these residues dramatically disrupts membrane fusion. Our data indicate that, through electrostatic interactions with a chloride ion, the asparagine residues promote assembly and profoundly stabilize the fusion-active structures that are required for viral envelope-mediated membrane fusion. Moreover, the BLV TM structure also reveals a charge-surrounded hydrophobic pocket on the central coiled coil and interactions with basic residues that cluster around this pocket are critical to membrane fusion and form a target for peptide inhibitors of envelope function. Charge-surrounded pockets and electrostatic interactions with small ions are common among class-1 fusion proteins, suggesting that small molecules that specifically target such motifs should prevent assembly of the trimer-of-hairpins and be of value as therapeutic inhibitors of viral entry.",2011 Feb 3,"['Lamb, Daniel', 'Schüttelkopf, Alexander W.', 'van Aalten, Daan M. F.', 'Brighty, David W.']",PLoS Pathog,,,True
12fe4cca998a403e153ae872595eab2676c77d2f,PMC,Phenotypic characteristics of human type II alveolar epithelial cells suitable for antigen presentation to T lymphocytes,http://dx.doi.org/10.1186/1465-9921-12-15,PMC3033824,21261956,CC BY,"BACKGROUND: Type II alveolar epithelial cells (AECII) are well known for their role in the innate immune system. More recently, it was proposed that they could play a role in the antigen presentation to T lymphocytes but contradictory results have been published both concerning their surface expressed molecules and the T lymphocyte responses in mixed lymphocyte cultures. The use of either AECII cell line or fresh cells could explain the observed discrepancies. Thus, this study aimed at defining the most relevant model of accessory antigen presenting cells by carefully comparing the two models for their expression of surface molecules necessary for efficient antigen presentation. METHODS: We have compared by flow cytometry the surface expression of the major markers involved in the immunological synapse on the A549 cell line, the most popular model of type II alveolar epithelial cells, and freshly isolated cells. HLA-DR, CD80, CD86, ICOS-L, CD54, CD58 surface expression were studied in resting conditions as well as after IFN-γ/TNF-α treatment, two inflammatory cytokines, known to modulate some of these markers. RESULTS: The major difference found between the two cells types was the very low surface expression of HLA-DR on the A549 cell line compared to its constitutive expression on freshly isolated AECII. The surface expression of co-stimulatory molecules from the B7 family was very low for the CD86 (B7-2) and ICOS-L (B7-H2) and absent for CD80 (B7-1) on both freshly isolated cells and A549 cell line. Neither IFN-γ nor TNF-α could increase the expression of these classical co-stimulatory molecules. However CD54 (ICAM-1) and CD58 (LFA-3) adhesion molecules, known to be implicated in B7 independent co-stimulatory signals, were well expressed on the two cell types. CONCLUSIONS: Constitutive expression of MHC class I and II molecules as well as alternative co-stimulatory molecules by freshly isolated AECII render these cells a good model to study antigen presentation.",2011 Jan 24,"['Corbière, Véronique', 'Dirix, Violette', 'Norrenberg, Sarah', 'Cappello, Mattéo', 'Remmelink, Myriam', 'Mascart, Françoise']",Respir Res,,,True
3b9e6b4d9ba3f58a882e5e25dd12d8aed9b5b4d4,PMC,Are there any differences in clinical and laboratory findings on admission between H1N1 positive and negative patients with flu-like symptoms?,http://dx.doi.org/10.1186/1756-0500-4-4,PMC3035198,21214902,CC BY,"BACKGROUND: The World Health Organization alert for the H1N1 influenza pandemic led to the implementation of certain measures regarding admission of patients with flu-like symptoms. All these instructions were adopted by the Greek National Health System. The aim of this study was to retrospectively examine the characteristics of all subjects admitted to the Unit of Infectious Diseases with symptoms indicating H1N1 infection, and to identify any differences between H1N1 positive or negative patients. Patients from the ED (emergency department) with flu-like symptoms (sore throat, cough, rhinorhea, or nasal congestion) and fever >37.5°C were admitted in the Unit of Infectious diseases and gave pharyngeal or nasopharyngeal swabs. Swabs were tested with real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR). FINDINGS: Patients were divided into two groups. Group A comprised 33 H1N1 positive patients and Group B (control group) comprised of 27 H1N1 negative patients. The two groups did not differ in terms of patient age, co-morbidities, length of hospitalization, temperature elevation, hypoxemia, as well as renal and liver function. There were also no significant differences in severity on admission. C-reactive protein (CRP) (mean 12.8 vs. 5.74) and white blood count (WBC) (mean 10.528 vs. 7.114) were significantly higher in group B than in group A upon admission. Obesity was noted in 8 patients of Group A (mean 31.67) and 14 patients of Group B (mean 37.78). Body mass index (BMI) was lower in H1N1 positive than in H1N1 negative patients (mean 31.67 vs. 37.78, respectively; p = 0.009). CONCLUSIONS: The majority of patients in both groups were young male adults. CRP, WBC and BMI were higher among H1N1 negative patients. Finally, clinical course of patients in both groups was mild and uneventful.",2011 Jan 7,"['Zarogoulidis, Paul', 'Constantinidis, Theodoros', 'Steiropoulos, Paschalis', 'Papanas, Nikolaos', 'Zarogoulidis, Kostas', 'Maltezos, Efstratios']",BMC Res Notes,,,True
9e0f14131900d5136cabf11f654a5cbb9d88ad48,PMC,Further Characterisation of the Translational Termination-Reinitiation Signal of the Influenza B Virus Segment 7 RNA,http://dx.doi.org/10.1371/journal.pone.0016822,PMC3035654,21347434,CC BY,"Termination-dependent reinitiation is used to co-ordinately regulate expression of the M1 and BM2 open-reading frames (ORFs) of the dicistronic influenza B segment 7 RNA. The start codon of the BM2 ORF overlaps the stop codon of the M1 ORF in the pentanucleotide UAA UG and ∼10% of ribosomes terminating at the M1 stop codon reinitiate translation at the overlapping AUG. BM2 synthesis requires the presence of, and translation through, 45 nt of RNA immediately upstream of the UAA UG, known as the ‘termination upstream ribosome binding site’ (TURBS). This region may tether ribosomal 40S subunits to the mRNA following termination and a short region of the TURBS, motif 1, with complementarity to helix 26 of 18S rRNA has been implicated in this process. Here, we provide further evidence for a direct interaction between mRNA and rRNA using antisense oligonucleotide targeting and functional analysis in yeast cells. The TURBS also binds initiation factor eIF3 and we show here that this protein stimulates reinitiation from both wild-type and defective TURBS when added exogenously, perhaps by stabilising ribosome-mRNA interactions. Further, we show that the position of the TURBS with respect to the UAA UG overlap is crucial, and that termination too far downstream of the 18S complementary sequence inhibits the process, probably due to reduced 40S tethering. However, in reporter mRNAs where the restart codon alone is moved downstream, termination-reinitiation is inhibited but not abolished, thus the site of reinitiation is somewhat flexible. Reinitiation on distant AUGs is not inhibited in eIF4G-depleted RRL, suggesting that the tethered 40S subunit can move some distance without a requirement for linear scanning.",2011 Feb 8,"['Powell, Michael L.', 'Leigh, Kendra E.', 'Pöyry, Tuija A. A.', 'Jackson, Richard J.', 'Brown, T. David K.', 'Brierley, Ian']",PLoS One,,,True
49ef14fbeee682057ed14674f623ca36c6d954cc,PMC,"RNA and DNA Bacteriophages as Molecular Diagnosis Controls in Clinical Virology: A Comprehensive Study of More than 45,000 Routine PCR Tests",http://dx.doi.org/10.1371/journal.pone.0016142,PMC3036576,21347398,CC BY,"Real-time PCR techniques are now commonly used for the detection of viral genomes in various human specimens and require for validation both external and internal controls (ECs and ICs). In particular, ICs added to clinical samples are necessary to monitor the extraction, reverse transcription, and amplification steps in order to detect false-negative results resulting from PCR-inhibition or errors in the technical procedure. Here, we performed a large scale evaluation of the use of bacteriophages as ICs in routine molecular diagnosis. This allowed to propose simple standardized procedures (i) to design specific ECs for both DNA and RNA viruses and (ii) to use T4 (DNA) or MS2 (RNA) phages as ICs in routine diagnosis. Various technical formats for using phages as ICs were optimised and validated. Subsequently, T4 and MS2 ICs were evaluated in routine real-time PCR or RT-PCR virological diagnostic tests, using a series of 8,950 clinical samples (representing 36 distinct specimen types) sent to our laboratory for the detection of a variety of DNA and RNA viruses. The frequency of inefficient detection of ICs was analyzed according to the nature of the sample. Inhibitors of enzymatic reactions were detected at high frequency in specific sample types such as heparinized blood and bone marrow (>70%), broncho-alveolar liquid (41%) and stools (36%). The use of T4 and MS2 phages as ICs proved to be cost-effective, flexible and adaptable to various technical procedures of real-time PCR detection in virology. It represents a valuable strategy for enhancing the quality of routine molecular diagnosis in laboratories that use in-house designed diagnostic systems, which can conveniently be associated to the use of specific synthetic ECs. The high rate of inhibitors observed in a variety of specimen types should stimulate the elaboration of improved technical protocols for the extraction and amplification of nucleic acids.",2011 Feb 9,"['Ninove, Laetitia', 'Nougairede, Antoine', 'Gazin, Celine', 'Thirion, Laurence', 'Delogu, Ilenia', 'Zandotti, Christine', 'Charrel, Remi N.', 'De Lamballerie, Xavier']",PLoS One,,,True
eb0fb44015f899d2b00fc41e9e65ea13fc7fcde1,PMC,Estimating the Economic Impact of Climate Change on Cardiovascular Diseases—Evidence from Taiwan,http://dx.doi.org/10.3390/ijerph7124250,PMC3037052,21318006,CC BY,"The main purpose of this study was to investigate how climate change affects blood vessel-related heart disease and hypertension and to estimate the associated economic damage. In this paper, both the panel data model and the contingent valuation method (CVM) approaches are applied. The empirical results indicate that the number of death from cardiovascular diseases would be increased by 0.226% as the variation in temperature increases by 1%. More importantly, the number of death from cardiovascular diseases would be increased by 1.2% to 4.1% under alternative IPCC climate change scenarios. The results from the CVM approach show that each person would be willing to pay US$51 to US$97 per year in order to avoid the increase in the mortality rate of cardiovascular diseases caused by climate change.",2010 Dec 17,"['Liao, Shu-Yi', 'Tseng, Wei-Chun', 'Chen, Pin-Yu', 'Chen, Chi-Chung', 'Wu, Wei-Min']",Int J Environ Res Public Health,,,True
4f3a25f455f5b0a76e0379e91f028a69de4be389,PMC,Knowledge and attitudes of healthcare workers in Chinese intensive care units regarding 2009 H1N1 influenza pandemic,http://dx.doi.org/10.1186/1471-2334-11-24,PMC3037318,21266085,CC BY,"BACKGROUND: To describe the knowledge and attitudes of critical care clinicians during the 2009 H1N1 influenza pandemic. METHODS: A survey conducted in 21 intensive care units in 17 provinces in China. RESULTS: Out of 733 questionnaires distributed, 695 were completed. Three hundred and fifty-six respondents (51.2%) reported their experience of caring for H1N1 patients. Despite the fact that 88.5% of all respondents ultimately finished an H1N1 training program, only 41.9% admitted that they had the knowledge of 2009 H1N1 influenza. A total of 572 respondents (82.3%) expressed willingness to care for H1N1 patients. Independent variables associated with increasing likelihood to care for patients in the logistic regression analysis were physicians or nurses rather than other professionals (odds ratio 4.056 and 3.235, p = 0.002 and 0.007, respectively), knowledge training prior to patient care (odds ratio 1.531, p = 0.044), and the confidence to know how to protect themselves and their patients (odds ratio 2.109, p = 0.001). CONCLUSION: Critical care clinicians reported poor knowledge of H1N1 influenza, even though most finished a relevant knowledge training program. Implementation of appropriate education program might improve compliance to infection control measures, and willingness to work in a pandemic.",2011 Jan 25,"['Ma, Xiaochun', 'He, Zhenyang', 'Wang, Yushan', 'Jiang, Li', 'Xu, Yuan', 'Qian, Chuanyun', 'Sun, Rongqing', 'Chen, Erzhen', 'Hu, Zhenjie', 'Zhou, Lihua', 'Zhou, Fachun', 'Qin, Tiehe', 'Cao, Xiangyuan', 'An, Youzhong', 'Sun, Renhua', 'Zhang, Xijing', 'Lin, Jiandong', 'Ai, Yuhang', 'Wu, Dawei', 'Du, Bin']",BMC Infect Dis,,,True
9bff285847e6573b613d937df23f57355afcbd5f,PMC,NS2 Protein of Hepatitis C Virus Interacts with Structural and Non-Structural Proteins towards Virus Assembly,http://dx.doi.org/10.1371/journal.ppat.1001278,PMC3037360,21347350,CC BY,"Growing experimental evidence indicates that, in addition to the physical virion components, the non-structural proteins of hepatitis C virus (HCV) are intimately involved in orchestrating morphogenesis. Since it is dispensable for HCV RNA replication, the non-structural viral protein NS2 is suggested to play a central role in HCV particle assembly. However, despite genetic evidences, we have almost no understanding about NS2 protein-protein interactions and their role in the production of infectious particles. Here, we used co-immunoprecipitation and/or fluorescence resonance energy transfer with fluorescence lifetime imaging microscopy analyses to study the interactions between NS2 and the viroporin p7 and the HCV glycoprotein E2. In addition, we used alanine scanning insertion mutagenesis as well as other mutations in the context of an infectious virus to investigate the functional role of NS2 in HCV assembly. Finally, the subcellular localization of NS2 and several mutants was analyzed by confocal microscopy. Our data demonstrate molecular interactions between NS2 and p7 and E2. Furthermore, we show that, in the context of an infectious virus, NS2 accumulates over time in endoplasmic reticulum-derived dotted structures and colocalizes with both the envelope glycoproteins and components of the replication complex in close proximity to the HCV core protein and lipid droplets, a location that has been shown to be essential for virus assembly. We show that NS2 transmembrane region is crucial for both E2 interaction and subcellular localization. Moreover, specific mutations in core, envelope proteins, p7 and NS5A reported to abolish viral assembly changed the subcellular localization of NS2 protein. Together, these observations indicate that NS2 protein attracts the envelope proteins at the assembly site and it crosstalks with non-structural proteins for virus assembly.",2011 Feb 10,"['Popescu, Costin-Ioan', 'Callens, Nathalie', 'Trinel, Dave', 'Roingeard, Philippe', 'Moradpour, Darius', 'Descamps, Véronique', 'Duverlie, Gilles', 'Penin, François', 'Héliot, Laurent', 'Rouillé, Yves', 'Dubuisson, Jean']",PLoS Pathog,,,True
86239535bbc306bd90a85a6145840c784fa35d82,PMC,Mitigation Strategies for Pandemic Influenza A: Balancing Conflicting Policy Objectives,http://dx.doi.org/10.1371/journal.pcbi.1001076,PMC3037387,21347316,CC BY,"Mitigation of a severe influenza pandemic can be achieved using a range of interventions to reduce transmission. Interventions can reduce the impact of an outbreak and buy time until vaccines are developed, but they may have high social and economic costs. The non-linear effect on the epidemic dynamics means that suitable strategies crucially depend on the precise aim of the intervention. National pandemic influenza plans rarely contain clear statements of policy objectives or prioritization of potentially conflicting aims, such as minimizing mortality (depending on the severity of a pandemic) or peak prevalence or limiting the socio-economic burden of contact-reducing interventions. We use epidemiological models of influenza A to investigate how contact-reducing interventions and availability of antiviral drugs or pre-pandemic vaccines contribute to achieving particular policy objectives. Our analyses show that the ideal strategy depends on the aim of an intervention and that the achievement of one policy objective may preclude success with others, e.g., constraining peak demand for public health resources may lengthen the duration of the epidemic and hence its economic and social impact. Constraining total case numbers can be achieved by a range of strategies, whereas strategies which additionally constrain peak demand for services require a more sophisticated intervention. If, for example, there are multiple objectives which must be achieved prior to the availability of a pandemic vaccine (i.e., a time-limited intervention), our analysis shows that interventions should be implemented several weeks into the epidemic, not at the very start. This observation is shown to be robust across a range of constraints and for uncertainty in estimates of both R(0) and the timing of vaccine availability. These analyses highlight the need for more precise statements of policy objectives and their assumed consequences when planning and implementing strategies to mitigate the impact of an influenza pandemic.",2011 Feb 10,"['Hollingsworth, T. Déirdre', 'Klinkenberg, Don', 'Heesterbeek, Hans', 'Anderson, Roy M.']",PLoS Comput Biol,,,True
4049f899668ea1ad76af00572962f030bae13756,PMC,Mitigation Strategies for Pandemic Influenza A: Balancing Conflicting Policy Objectives,http://dx.doi.org/10.1371/journal.pcbi.1001076,PMC3037387,21347316,CC BY,"Mitigation of a severe influenza pandemic can be achieved using a range of interventions to reduce transmission. Interventions can reduce the impact of an outbreak and buy time until vaccines are developed, but they may have high social and economic costs. The non-linear effect on the epidemic dynamics means that suitable strategies crucially depend on the precise aim of the intervention. National pandemic influenza plans rarely contain clear statements of policy objectives or prioritization of potentially conflicting aims, such as minimizing mortality (depending on the severity of a pandemic) or peak prevalence or limiting the socio-economic burden of contact-reducing interventions. We use epidemiological models of influenza A to investigate how contact-reducing interventions and availability of antiviral drugs or pre-pandemic vaccines contribute to achieving particular policy objectives. Our analyses show that the ideal strategy depends on the aim of an intervention and that the achievement of one policy objective may preclude success with others, e.g., constraining peak demand for public health resources may lengthen the duration of the epidemic and hence its economic and social impact. Constraining total case numbers can be achieved by a range of strategies, whereas strategies which additionally constrain peak demand for services require a more sophisticated intervention. If, for example, there are multiple objectives which must be achieved prior to the availability of a pandemic vaccine (i.e., a time-limited intervention), our analysis shows that interventions should be implemented several weeks into the epidemic, not at the very start. This observation is shown to be robust across a range of constraints and for uncertainty in estimates of both R(0) and the timing of vaccine availability. These analyses highlight the need for more precise statements of policy objectives and their assumed consequences when planning and implementing strategies to mitigate the impact of an influenza pandemic.",2011 Feb 10,"['Hollingsworth, T. Déirdre', 'Klinkenberg, Don', 'Heesterbeek, Hans', 'Anderson, Roy M.']",PLoS Comput Biol,,,False
bf1b9188ca2e3eb5e80b73dcf3c12799344a7199,PMC,"Short Term Effects of Weather on Hand, Foot and Mouth Disease",http://dx.doi.org/10.1371/journal.pone.0016796,PMC3037951,21347303,CC BY,"BACKGROUND: Hand, foot, and mouth disease (HFMD) outbreaks leading to clinical and fatal complications have increased since late 1990s; especially in the Asia Pacific Region. Outbreaks of HFMD peaks in the warmer season of the year, but the underlying factors for this annual pattern and the reasons to the recent upsurge trend have not yet been established. This study analyzed the effect of short-term changes in weather on the incidence of HFMD in Singapore. METHODS: The relative risks between weekly HFMD cases and temperature and rainfall were estimated for the period 2001–2008 using time series Poisson regression models allowing for over-dispersion. Smoothing was used to allow non-linear relationship between weather and weekly HFMD cases, and to adjust for seasonality and long-term time trend. Additionally, autocorrelation was controlled and weather was allowed to have a lagged effect on HFMD incidence up to 2 weeks. RESULTS: Weekly temperature and rainfall showed statistically significant association with HFMD incidence at time lag of 1–2 weeks. Every 1°C increases in maximum temperature above 32°C elevated the risk of HFMD incidence by 36% (95% CI = 1.341–1.389). Simultaneously, one mm increase of weekly cumulative rainfall below 75 mm increased the risk of HFMD by 0.3% (CI = 1.002–1.003). While above 75 mm the effect was opposite and each mm increases of rainfall decreased the incidence by 0.5% (CI = 0.995–0.996). We also found that a difference between minimum and maximum temperature greater than 7°C elevated the risk of HFMD by 41% (CI = 1.388–1.439). CONCLUSION: Our findings suggest a strong association between HFMD and weather. However, the exact reason for the association is yet to be studied. Information on maximum temperature above 32°C and moderate rainfall precede HFMD incidence could help to control and curb the up-surging trend of HFMD.",2011 Feb 11,"['Hii, Yien Ling', 'Rocklöv, Joacim', 'Ng, Nawi']",PLoS One,,,True
4c6a45d1e56660fa713b637825b96e287a0acef5,PMC,Experimental infection of dogs with a feline endogenous retrovirus RD-114,http://dx.doi.org/10.1186/1751-0147-53-3,PMC3038973,21269522,CC BY,"BACKGROUND: The feline endogenous retrovirus RD114 is contained in the genome of cats. The virus may contaminate live canine vaccines based on cultured feline cells. The in vivo infectivity, acute and subacute pathogenicity, and viral proliferation of the RD114 virus were evaluated by experimental infection of dogs. METHODS: Nine specific pathogen free dogs were divided into three groups, with each group consisting of one female and two male dogs. Dogs were subcutaneously inoculated in the neck with either 1 ml RD114 stock virus (group A), inactivated RD114 virus suspension (group B), or cell culture medium (group C) as a negative control. To assess blood cell counts and biochemical properties, blood samples from each group were collected 5 days before inoculation, just prior to inoculation, and 1, 3, 7 and 10 days post-inoculation. RESULT: During the experimental period of 51 days, none of the dogs inoculated with RD114 virus showed any clinical signs, significant increases in rectal temperature or abnormal blood biochemical characteristics including C-reactive protein when compared with the negative controls. We were not able to re-isolate the RD114 virus from buffy coat cells of group A dogs. Additionally, we could not detect RD114 provirus in the genomic DNA isolated from peripheral blood leukocytes, lymph node, spleen and sternal bone marrow cells. CONCLUSIONS: Signs of RD114 virus proliferation were not found after subcutaneous infection of dogs. Although the potential risk caused by infection with RD114 virus in dogs could not be assessed in this study, we suspect that RD114 virus has little or no virulence in dogs.",2011 Jan 27,"['Narushima, Rie', 'Horiuchi, Noriyuki', 'Usui, Tatsufumi', 'Ogawa, Takashi', 'Takahashi, Toshio', 'Shimazaki, Tomoaki']",Acta Vet Scand,,,True
cfb06153bd9db651c6c7c268aecf6e65113fe008,PMC,PLP2 of Mouse Hepatitis Virus A59 (MHV-A59) Targets TBK1 to Negatively Regulate Cellular Type I Interferon Signaling Pathway,http://dx.doi.org/10.1371/journal.pone.0017192,PMC3041802,21364999,CC BY,"BACKGROUND: Coronaviruses such as severe acute respiratory syndrome (SARS) coronavirus (SCoV) and mouse hepatitis virus A59 (MHV-A59) have evolved strategies to disable the innate immune system for productive replication and spread of infection. We have previously shown that papain-like protease domain 2 (PLP2), a catalytic domain of the nonstructural protein 3 (nsp3) of MHV-A59, encodes a deubiquitinase (DUB) and inactivates IFN regulatory factor 3 (IRF3) thereby the type I interferon (IFN) response. PRINCIPAL FINDINGS: Here we provide further evidence that PLP2 may also target TANK-binding kinase-1 (TBK1), the upstream kinase of IRF3 in the IFN signaling pathway. Overexpression experiments showed that PLP2 deubiquitinated TBK1 and reduced its kinase activity, hence inhibited IFN-β reporter activity. Albeit promiscuous in deubiquitinating cellular proteins, PLP2 inactivated TBK1 and IFN-β response in TNF receptor associated factor 3 (TRAF3) deficient cells, suggesting that targeting TBK1 would be sufficient for PLP2 to inhibit IRF3 activation. This notion was further supported by in vitro kinase assays, in which prior treatment of TBK1 with PLP2 inhibited its kinase activity to phosphorylate IRF3. Intriguing enough, results of PLP2 overexpression system and MHV-A59 infection system proved that PLP2 formed an inactive complex with TBK1 and IRF3 in the cytoplasm and the presence of PLP2 stabilized the hypo-phosphorylated IRF3-TBK1 complex in a dose-dependent manner. CONCLUSIONS: These results suggest that PLP2 not only inactivates TBK1, but also prevents IRF3 nuclear translocation hence inhibits IFN transcription activation. Identification of the conserved DUB activity of PLP2 in suppression of IFN signaling would provide a useful clue to the development of therapeutics against coronaviruses infection.",2011 Feb 18,"['Wang, Gang', 'Chen, Gang', 'Zheng, Dahai', 'Cheng, Genhong', 'Tang, Hong']",PLoS One,,,True
6606f7964096d15ffdcb9772acbe40ae415dcb97,PMC,Update on the management of acute pharyngitis in children,http://dx.doi.org/10.1186/1824-7288-37-10,PMC3042010,21281502,CC BY,"Streptococcal pharyngitis is a very common pathology in paediatric age all over the world. Nevertheless there isn't a joint agreement on the management of this condition. Some authors recommend to perform a microbiological investigation in suspected bacterial cases in order to treat the confirmed cases with antibiotics so to prevent suppurative complications and acute rheumatic fever. Differently, other authors consider pharyngitis, even streptococcal one, a benign, self-limiting disease. Consequently they wouldn't routinely perform microbiological tests and, pointing to a judicious use of antibiotics, they would reserve antimicrobial treatment to well-selected cases. It has been calculated that the number of patients needed to treat to prevent one complication after upper respiratory tract infections (including sore throat), was over 4000. Even the use of the Centor score, in order to evaluate the risk of streptococcal infection, is under debate and the interpretation of the test results may vary considerably. Penicillin is considered all over the world as first line treatment, but oral amoxicillin is also accepted and, due to its better palatability, can be a suitable option. Macrolides should be reserved to the rare cases of proved allergy to β-lactams. Cephalosporins can be used in patients allergic to penicillin (with the exception of type I hypersensibility) and have been also proposed to treat the relapses.",2011 Jan 31,"['Regoli, Marta', 'Chiappini, Elena', 'Bonsignori, Francesca', 'Galli, Luisa', 'de Martino, Maurizio']",Ital J Pediatr,,,True
2a90543a82ae4b2916e12f6294b7a37aa8142942,PMC,Twelve years' detection of respiratory viruses by immunofluorescence in hospitalised children: impact of the introduction of a new respiratory picornavirus assay,http://dx.doi.org/10.1186/1471-2334-11-41,PMC3044667,21299840,CC BY,"BACKGROUND: Direct immunofluorescence assays (DFA) are a rapid and inexpensive method for the detection of respiratory viruses and may therefore be used for surveillance. Few epidemiological studies have been published based solely on DFA and none included respiratory picornaviruses and human metapneumovirus (hMPV). We wished to evaluate the use of DFA for epidemiological studies with a long-term observation of respiratory viruses that includes both respiratory picornaviruses and hMPV. METHODS: Since 1998 all children hospitalized with respiratory illness at the University Hospital Bern have been screened with DFA for common respiratory viruses including adenovirus, respiratory syncytial virus (RSV), influenza A and B, and parainfluenza virus 1-3. In 2006 assays for respiratory picornaviruses and hMPV were added. Here we describe the epidemiological pattern for these respiratory viruses detected by DFA in 10'629 nasopharyngeal aspirates collected from 8'285 patients during a 12-year period (1998-2010). RESULTS: Addition of assays for respiratory picornaviruses and hMPV raised the proportion of positive DFA results from 35% to 58% (p < 0.0001). Respiratory picornaviruses were the most common viruses detected among patients ≥1 year old. The seasonal patterns and age distribution for the studied viruses agreed well with those reported in the literature. In 2010, an hMPV epidemic of unexpected size was observed. CONCLUSIONS: DFA is a valid, rapid, flexible and inexpensive method. The addition of assays for respiratory picornaviruses and hMPV broadens its range of viral detection. DFA is, even in the ""PCR era"", a particularly adapted method for the long term surveillance of respiratory viruses in a pediatric population.",2011 Feb 7,"['Sadeghi, Christine D', 'Aebi, Christoph', 'Gorgievski-Hrisoho, Meri', 'Mühlemann, Kathrin', 'Barbani, Maria Teresa']",BMC Infect Dis,,,True
ac99b803a90e235412c73efa91894e9a1ed3f019,PMC,NIH Disease Funding Levels and Burden of Disease,http://dx.doi.org/10.1371/journal.pone.0016837,PMC3044706,21383981,CC BY,"BACKGROUND: An analysis of NIH funding in 1996 found that the strongest predictor of funding, disability-adjusted life-years (DALYs), explained only 39% of the variance in funding. In 1998, Congress requested that the Institute of Medicine (IOM) evaluate priority-setting criteria for NIH funding; the IOM recommended greater consideration of disease burden. We examined whether the association between current burden and funding has changed since that time. METHODS: We analyzed public data on 2006 NIH funding for 29 common conditions. Measures of US disease burden in 2004 were obtained from the World Health Organization's Global Burden of Disease study and national databases. We assessed the relationship between disease burden and NIH funding dollars in univariate and multivariable log-linear models that evaluated all measures of disease burden. Sensitivity analyses examined associations with future US burden, current and future measures of world disease burden, and a newly standardized NIH accounting method. RESULTS: In univariate and multivariable analyses, disease-specific NIH funding levels increased with burden of disease measured in DALYs (p = 0.001), which accounted for 33% of funding level variation. No other factor predicted funding in multivariable models. Conditions receiving the most funding greater than expected based on disease burden were AIDS ($2474 M), diabetes mellitus ($390 M), and perinatal conditions ($297 M). Depression ($719 M), injuries ($691 M), and chronic obstructive pulmonary disease ($613 M) were the most underfunded. Results were similar using estimates of future US burden, current and future world disease burden, and alternate NIH accounting methods. CONCLUSIONS: Current levels of NIH disease-specific research funding correlate modestly with US disease burden, and correlation has not improved in the last decade.",2011 Feb 24,"['Gillum, Leslie A.', 'Gouveia, Christopher', 'Dorsey, E. Ray', 'Pletcher, Mark', 'Mathers, Colin D.', 'McCulloch, Charles E.', 'Johnston, S. Claiborne']",PLoS One,,,True
164f0fed97b05b34ea5df0f4e4e9e204d05f7849,PMC,Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes,http://dx.doi.org/10.1371/journal.pone.0017324,PMC3044746,21390319,CC BY,"This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content.",2011 Feb 24,"['Zhou, Jun-Wei', 'Tsui, Stephen K. W.', 'Ng, Maggie C. Y.', 'Geng, Hua', 'Li, Sai-Kam', 'So, Wing-Yee', 'Ma, Ronald C.', 'Wang, Ying', 'Tao, Qian', 'Chen, Zhen-Yu', 'Chan, Juliana C. N.', 'Ho, Yuan-Yuan']",PLoS One,,,True
4594720a38546b67cb9a8f2ec9e9a7bee2620e78,PMC,Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes,http://dx.doi.org/10.1371/journal.pone.0017324,PMC3044746,21390319,CC BY,"This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content.",2011 Feb 24,"['Zhou, Jun-Wei', 'Tsui, Stephen K. W.', 'Ng, Maggie C. Y.', 'Geng, Hua', 'Li, Sai-Kam', 'So, Wing-Yee', 'Ma, Ronald C.', 'Wang, Ying', 'Tao, Qian', 'Chen, Zhen-Yu', 'Chan, Juliana C. N.', 'Ho, Yuan-Yuan']",PLoS One,,,False
47025519790a04e4fae85f0b8d3b6f0949d9294f,PMC,Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes,http://dx.doi.org/10.1371/journal.pone.0017324,PMC3044746,21390319,CC BY,"This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content.",2011 Feb 24,"['Zhou, Jun-Wei', 'Tsui, Stephen K. W.', 'Ng, Maggie C. Y.', 'Geng, Hua', 'Li, Sai-Kam', 'So, Wing-Yee', 'Ma, Ronald C.', 'Wang, Ying', 'Tao, Qian', 'Chen, Zhen-Yu', 'Chan, Juliana C. N.', 'Ho, Yuan-Yuan']",PLoS One,,,False
e09fce29eff5b8f7689858355e94daaa15fe36dc,PMC,Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes,http://dx.doi.org/10.1371/journal.pone.0017324,PMC3044746,21390319,CC BY,"This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content.",2011 Feb 24,"['Zhou, Jun-Wei', 'Tsui, Stephen K. W.', 'Ng, Maggie C. Y.', 'Geng, Hua', 'Li, Sai-Kam', 'So, Wing-Yee', 'Ma, Ronald C.', 'Wang, Ying', 'Tao, Qian', 'Chen, Zhen-Yu', 'Chan, Juliana C. N.', 'Ho, Yuan-Yuan']",PLoS One,,,False
80f7035e6e260377efa2f734629b96d01195d3ea,PMC,Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes,http://dx.doi.org/10.1371/journal.pone.0017324,PMC3044746,21390319,CC BY,"This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content.",2011 Feb 24,"['Zhou, Jun-Wei', 'Tsui, Stephen K. W.', 'Ng, Maggie C. Y.', 'Geng, Hua', 'Li, Sai-Kam', 'So, Wing-Yee', 'Ma, Ronald C.', 'Wang, Ying', 'Tao, Qian', 'Chen, Zhen-Yu', 'Chan, Juliana C. N.', 'Ho, Yuan-Yuan']",PLoS One,,,False
d68205dc527d5f0ee5a9ece74f3e7a7b22af8402,PMC,Dynamically-Driven Inactivation of the Catalytic Machinery of the SARS 3C-Like Protease by the N214A Mutation on the Extra Domain,http://dx.doi.org/10.1371/journal.pcbi.1001084,PMC3044768,21390281,CC BY,"Despite utilizing the same chymotrypsin fold to host the catalytic machinery, coronavirus 3C-like proteases (3CLpro) noticeably differ from picornavirus 3C proteases in acquiring an extra helical domain in evolution. Previously, the extra domain was demonstrated to regulate the catalysis of the SARS-CoV 3CLpro by controlling its dimerization. Here, we studied N214A, another mutant with only a doubled dissociation constant but significantly abolished activity. Unexpectedly, N214A still adopts the dimeric structure almost identical to that of the wild-type (WT) enzyme. Thus, we conducted 30-ns molecular dynamics (MD) simulations for N214A, WT, and R298A which we previously characterized to be a monomer with the collapsed catalytic machinery. Remarkably, three proteases display distinctive dynamical behaviors. While in WT, the catalytic machinery stably retains in the activated state; in R298A it remains largely collapsed in the inactivated state, thus implying that two states are not only structurally very distinguishable but also dynamically well separated. Surprisingly, in N214A the catalytic dyad becomes dynamically unstable and many residues constituting the catalytic machinery jump to sample the conformations highly resembling those of R298A. Therefore, the N214A mutation appears to trigger the dramatic change of the enzyme dynamics in the context of the dimeric form which ultimately inactivates the catalytic machinery. The present MD simulations represent the longest reported so far for the SARS-CoV 3CLpro, unveiling that its catalysis is critically dependent on the dynamics, which can be amazingly modulated by the extra domain. Consequently, mediating the dynamics may offer a potential avenue to inhibit the SARS-CoV 3CLpro.",2011 Feb 24,"['Shi, Jiahai', 'Han, Nanyu', 'Lim, Liangzhong', 'Lua, Shixiong', 'Sivaraman, J.', 'Wang, Lushan', 'Mu, Yuguang', 'Song, Jianxing']",PLoS Comput Biol,,,True
cd33661bfe3aa8e73dc1cd196c34b4eea22d6e4e,PMC,Dynamically-Driven Inactivation of the Catalytic Machinery of the SARS 3C-Like Protease by the N214A Mutation on the Extra Domain,http://dx.doi.org/10.1371/journal.pcbi.1001084,PMC3044768,21390281,CC BY,"Despite utilizing the same chymotrypsin fold to host the catalytic machinery, coronavirus 3C-like proteases (3CLpro) noticeably differ from picornavirus 3C proteases in acquiring an extra helical domain in evolution. Previously, the extra domain was demonstrated to regulate the catalysis of the SARS-CoV 3CLpro by controlling its dimerization. Here, we studied N214A, another mutant with only a doubled dissociation constant but significantly abolished activity. Unexpectedly, N214A still adopts the dimeric structure almost identical to that of the wild-type (WT) enzyme. Thus, we conducted 30-ns molecular dynamics (MD) simulations for N214A, WT, and R298A which we previously characterized to be a monomer with the collapsed catalytic machinery. Remarkably, three proteases display distinctive dynamical behaviors. While in WT, the catalytic machinery stably retains in the activated state; in R298A it remains largely collapsed in the inactivated state, thus implying that two states are not only structurally very distinguishable but also dynamically well separated. Surprisingly, in N214A the catalytic dyad becomes dynamically unstable and many residues constituting the catalytic machinery jump to sample the conformations highly resembling those of R298A. Therefore, the N214A mutation appears to trigger the dramatic change of the enzyme dynamics in the context of the dimeric form which ultimately inactivates the catalytic machinery. The present MD simulations represent the longest reported so far for the SARS-CoV 3CLpro, unveiling that its catalysis is critically dependent on the dynamics, which can be amazingly modulated by the extra domain. Consequently, mediating the dynamics may offer a potential avenue to inhibit the SARS-CoV 3CLpro.",2011 Feb 24,"['Shi, Jiahai', 'Han, Nanyu', 'Lim, Liangzhong', 'Lua, Shixiong', 'Sivaraman, J.', 'Wang, Lushan', 'Mu, Yuguang', 'Song, Jianxing']",PLoS Comput Biol,,,False
da2b409352de17f4c628991dfdf715a08c0d865e,PMC,Dynamically-Driven Inactivation of the Catalytic Machinery of the SARS 3C-Like Protease by the N214A Mutation on the Extra Domain,http://dx.doi.org/10.1371/journal.pcbi.1001084,PMC3044768,21390281,CC BY,"Despite utilizing the same chymotrypsin fold to host the catalytic machinery, coronavirus 3C-like proteases (3CLpro) noticeably differ from picornavirus 3C proteases in acquiring an extra helical domain in evolution. Previously, the extra domain was demonstrated to regulate the catalysis of the SARS-CoV 3CLpro by controlling its dimerization. Here, we studied N214A, another mutant with only a doubled dissociation constant but significantly abolished activity. Unexpectedly, N214A still adopts the dimeric structure almost identical to that of the wild-type (WT) enzyme. Thus, we conducted 30-ns molecular dynamics (MD) simulations for N214A, WT, and R298A which we previously characterized to be a monomer with the collapsed catalytic machinery. Remarkably, three proteases display distinctive dynamical behaviors. While in WT, the catalytic machinery stably retains in the activated state; in R298A it remains largely collapsed in the inactivated state, thus implying that two states are not only structurally very distinguishable but also dynamically well separated. Surprisingly, in N214A the catalytic dyad becomes dynamically unstable and many residues constituting the catalytic machinery jump to sample the conformations highly resembling those of R298A. Therefore, the N214A mutation appears to trigger the dramatic change of the enzyme dynamics in the context of the dimeric form which ultimately inactivates the catalytic machinery. The present MD simulations represent the longest reported so far for the SARS-CoV 3CLpro, unveiling that its catalysis is critically dependent on the dynamics, which can be amazingly modulated by the extra domain. Consequently, mediating the dynamics may offer a potential avenue to inhibit the SARS-CoV 3CLpro.",2011 Feb 24,"['Shi, Jiahai', 'Han, Nanyu', 'Lim, Liangzhong', 'Lua, Shixiong', 'Sivaraman, J.', 'Wang, Lushan', 'Mu, Yuguang', 'Song, Jianxing']",PLoS Comput Biol,,,False
5303b7430b20a5e665f7cadd07ae77baa5687e73,PMC,Statistical learning techniques applied to epidemiology: a simulated case-control comparison study with logistic regression,http://dx.doi.org/10.1186/1471-2105-12-37,PMC3045299,21272346,CC BY,"BACKGROUND: When investigating covariate interactions and group associations with standard regression analyses, the relationship between the response variable and exposure may be difficult to characterize. When the relationship is nonlinear, linear modeling techniques do not capture the nonlinear information content. Statistical learning (SL) techniques with kernels are capable of addressing nonlinear problems without making parametric assumptions. However, these techniques do not produce findings relevant for epidemiologic interpretations. A simulated case-control study was used to contrast the information embedding characteristics and separation boundaries produced by a specific SL technique with logistic regression (LR) modeling representing a parametric approach. The SL technique was comprised of a kernel mapping in combination with a perceptron neural network. Because the LR model has an important epidemiologic interpretation, the SL method was modified to produce the analogous interpretation and generate odds ratios for comparison. RESULTS: The SL approach is capable of generating odds ratios for main effects and risk factor interactions that better capture nonlinear relationships between exposure variables and outcome in comparison with LR. CONCLUSIONS: The integration of SL methods in epidemiology may improve both the understanding and interpretation of complex exposure/disease relationships.",2011 Jan 27,"['Heine, John J', 'Land, Walker H', 'Egan, Kathleen M']",BMC Bioinformatics,,,True
4c45bdd7e23c8ea6b0dfb04d48a5ceda8f022597,PMC,Non-Invasive Microstructure and Morphology Investigation of the Mouse Lung: Qualitative Description and Quantitative Measurement,http://dx.doi.org/10.1371/journal.pone.0017400,PMC3045447,21364899,CC BY,"BACKGROUND: Early detection of lung cancer is known to improve the chances of successful treatment. However, lungs are soft tissues with complex three-dimensional configuration. Conventional X-ray imaging is based purely on absorption resulting in very low contrast when imaging soft tissues without contrast agents. It is difficult to obtain adequate information of lung lesions from conventional X-ray imaging. METHODS: In this study, a recently emerged imaging technique, in-line X-ray phase contrast imaging (IL-XPCI) was used. This powerful technique enabled high-resolution investigations of soft tissues without contrast agents. We applied IL-XPCI to observe the lungs in an intact mouse for the purpose of defining quantitatively the micro-structures in lung. FINDINGS: The three-dimensional model of the lung was successfully established, which provided an excellent view of lung airways. We highlighted the use of IL-XPCI in the visualization and assessment of alveoli which had rarely been studied in three dimensions (3D). The precise view of individual alveolus was achieved. The morphological parameters, such as diameter and alveolar surface area were measured. These parameters were of great importance in the diagnosis of diseases related to alveolus and alveolar scar. CONCLUSION: Our results indicated that IL-XPCI had the ability to represent complex anatomical structures in lung. This offered a new perspective on the diagnosis of respiratory disease and may guide future work in the study of respiratory mechanism on the alveoli level.",2011 Feb 25,"['Zhang, Lu', 'Li, Dongyue', 'Luo, Shuqian']",PLoS One,,,True
bafbd40e253b24fc6b10b66bf68fe838e0a6a313,PMC,Variability and Diversity of Nasopharyngeal Microbiota in Children: A Metagenomic Analysis,http://dx.doi.org/10.1371/journal.pone.0017035,PMC3046172,21386965,CC BY,"The nasopharynx is the ecological niche for many commensal bacteria and for potential respiratory or invasive pathogens like Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. Disturbance of a balanced nasopharyngeal (NP) microbiome might be involved in the onset of symptomatic infections with these pathogens, which occurs primarily in fall and winter. It is unknown whether seasonal infection patterns are associated with concomitant changes in NP microbiota. As young children are generally prone to respiratory and invasive infections, we characterized the NP microbiota of 96 healthy children by barcoded pyrosequencing of the V5–V6 hypervariable region of the 16S-rRNA gene, and compared microbiota composition between children sampled in winter/fall with children sampled in spring. The approximately 1000000 sequences generated represented 13 taxonomic phyla and approximately 250 species-level phyla types (OTUs). The 5 most predominant phyla were Proteobacteria (64%), Firmicutes (21%), Bacteroidetes (11%), Actinobacteria (3%) and Fusobacteria (1,4%) with Moraxella, Haemophilus, Streptococcus, Flavobacteria, Dolosigranulum, Corynebacterium and Neisseria as predominant genera. The inter-individual variability was that high that on OTU level a core microbiome could not be defined. Microbiota profiles varied strongly with season, with in fall/winter a predominance of Proteobacteria (relative abundance (% of all sequences): 75% versus 51% in spring) and Fusobacteria (absolute abundance (% of children): 14% versus 2% in spring), and in spring a predominance of Bacteroidetes (relative abundance: 19% versus 3% in fall/winter, absolute abundance: 91% versus 54% in fall/winter), and Firmicutes. The latter increase is mainly due to (Brevi)bacillus and Lactobacillus species (absolute abundance: 96% versus 10% in fall/winter) which are like Bacteroidetes species generally related to healthy ecosystems. The observed seasonal effects could not be attributed to recent antibiotics or viral co-infection. The NP microbiota of young children is highly diverse and appears different between seasons. These differences seem independent of antibiotic use or viral co-infection.",2011 Feb 28,"['Bogaert, Debby', 'Keijser, Bart', 'Huse, Susan', 'Rossen, John', 'Veenhoven, Reinier', 'van Gils, Elske', 'Bruin, Jacob', 'Montijn, Roy', 'Bonten, Marc', 'Sanders, Elisabeth']",PLoS One,,,True
5cd3d3edd1b68bce986c6b9e6bfa9720efd041e3,PMC,A rebuttal to the comments on the genome order index and the Z-curve,http://dx.doi.org/10.1186/1745-6150-6-10,PMC3046898,21324187,CC BY,"BACKGROUND: Elhaik, Graur and Josic recently commented on the genome order index (S) and the Z-curve (Elhaik et al. Biol Direct 2010, 5: 10). S is a quantity defined as S = a(2 )+ c(2 )+ g(2 )+ t(2), where a, c, g and t denote corresponding base frequencies. The Z-curve is a three dimensional curve that represents a DNA sequence in the manner that each can be uniquely reconstructed given the other. Elhaik et al. made 4 major claims. 1) In the previous mapping system with the regular tetrahedron, calculation of the radius of the inscribed sphere is ""a mathematical error"". 2) S follows an exponential distribution and is narrowly distributed with a range of (0.25 - 0.33). 3) Based on the Chargaff's second parity rule (PR2), ""S is equivalent to H [Shannon entropy]"" and they are derivable from each other. 4) Z-curve ""suffers from over dimensionality"", because based on the analysis of 235 bacterial genomes, x and y components contributed only less than 1% of the variance and therefore ""would be of little use"". RESULTS: 1) Elhaik et al. mistakenly neglected the parameter [Formula: see text] when calculating the radius of the inscribed sphere. 2) The exponential distribution of S is a restatement of our previous conclusion, and the range of (0.25 - 0.33) only paraphrases the previously suggested S range (0.25 -1/3). 3) Elhaik et al. incorrectly disregard deviations from PR2 by treating the deviations as 0 altogether, reduce S and H, both having 4 variables, a, c, g and t, into functions of one single variable, a only, and apply this treatment to all DNA sequences as the basis of their ""demonstration"", which is therefore invalid. 4) Elhaik et al. confuse numeral smallness with biological insignificance, and disregard the distributions of purine/pyrimidine and amino/keto bases (x and y components), the variations of which, although can be less than that of GC content, contain rich information that is important and useful, such as in locating replication origins of bacterial and archaeal genomes, and in studies of gene recognition in various species. CONCLUSION: Elhaik et al. confuse S (a single number) with Z-curve (a series of 3D coordinates), which are distinct. To use S as a case study of Z-curve, by itself, is invalid. S and H are neither equivalent nor derivable from each other. The criticisms of Elhaik, Graur and Josic are wrong. REVIEWERS: This article was reviewed by Erik van Nimwegen.",2011 Feb 16,"Zhang, Ren",Biol Direct,,,True
e42218bb9ddb954382e0db792ffeae988bf62545,PMC,"Large-scale seroprevalence analysis of human metapneumovirus and human respiratory syncytial virus infections in Beijing, China",http://dx.doi.org/10.1186/1743-422X-8-62,PMC3046927,21310026,CC BY,"BACKGROUND: Human metapneumovirus (hMPV), a recently identified virus, causes acute respiratory tract infections (ARTIs) in infants and children. However, studies on the seroepidemeology of hMPV are very limited in China. To assess the seroprevalence of hMPV infection in China, we tested a total of 1,156 serum specimens for the presence of anti-hMPV IgG antibody in children and adults free of acute respiratory illness in Beijing, China by using hMPV nucleocapsid (N) protein as an antigen. As a control, we used the human serum antibody against the N protein of human respiratory syncytial virus (hRSV), the most important viral agent responsible for ARIs in children. RESULTS: The seropositive rate for hMPV increased steadily with age from 67% at 1-6 mo to 100% at age 20. However, the rate dropped slightly between 6 mo and 1 yr of age. The seropositive rate for hRSV also increased steadily with age from 71% at 1-6 mo to 100% at age 20. In children aged six months to six years, the seropositive rates for the anti-hRSV IgG antibody were significantly higher than those for hMPV. Additionally, IgG antibody titers to hMPV and hRSV were significantly higher in adults than in young children. Consistent with the seropositive rates, the geometric mean titer of anti-hMPV IgG antibody was lower than that of anti-hRSV IgG antibody in children aged six months to six years. CONCLUSIONS: Our results indicate that similar to hRSV, exposure to hMPV is ubiquitous in the Beijing population. However, the seroprevalence of anti-hMPV IgG antibody is lower than that of hRSV in children between six months and six years old, which suggests a different number of repeat infections or a different response to infections.",2011 Feb 10,"['Lu, Guilan', 'Gonzalez, Richard', 'Guo, Li', 'Wu, Chao', 'Wu, Jiang', 'Vernet, Guy', 'Paranhos-Baccalà, Gláucia', 'Wang, Jianwei', 'Hung, Tao']",Virol J,,,True
79979652a864cef3a41342ccb1add48e5ad0cf85,PMC,Plant Plastid Engineering,http://dx.doi.org/10.2174/138920210793175912,PMC3048312,21532834,CC BY,"Genetic material in plants is distributed into nucleus, plastids and mitochondria. Plastid has a central role of carrying out photosynthesis in plant cells. Plastid transformation is becoming more popular and an alternative to nuclear gene transformation because of various advantages like high protein levels, the feasibility of expressing multiple proteins from polycistronic mRNAs, and gene containment through the lack of pollen transmission. Recently, much progress in plastid engineering has been made. In addition to model plant tobacco, many transplastomic crop plants have been generated which possess higher resistance to biotic and abiotic stresses and molecular pharming. In this mini review, we will discuss the features of the plastid DNA and advantages of plastid transformation. We will also present some examples of transplastomic plants developed so far through plastid engineering, and the various applications of plastid transformation.",2010 Nov,"['Wani, Shabir H.', 'Haider, Nadia', 'Kumar, Hitesh', 'Singh, N.B.']",Curr Genomics,,,True
258b69aa1d0bb32cf913f8124f8c053442522f6b,PMC,"Viral Etiology of Influenza-Like Illnesses in Antananarivo, Madagascar, July 2008 to June 2009",http://dx.doi.org/10.1371/journal.pone.0017579,PMC3048401,21390235,CC BY,"BACKGROUND: In Madagascar, despite an influenza surveillance established since 1978, little is known about the etiology and prevalence of viruses other than influenza causing influenza-like illnesses (ILIs). METHODOLOGY/PRINCIPAL FINDINGS: From July 2008 to June 2009, we collected respiratory specimens from patients who presented ILIs symptoms in public and private clinics in Antananarivo (the capital city of Madagascar). ILIs were defined as body temperature ≥38°C and cough and at least two of the following symptoms: sore throat, rhinorrhea, headache and muscular pain, for a maximum duration of 3 days. We screened these specimens using five multiplex real time Reverse Transcription and/or Polymerase Chain Reaction assays for detection of 14 respiratory viruses. We detected respiratory viruses in 235/313 (75.1%) samples. Overall influenza virus A (27.3%) was the most common virus followed by rhinovirus (24.8%), RSV (21.2%), adenovirus (6.1%), coronavirus OC43 (6.1%), influenza virus B (3.9%), parainfluenza virus-3 (2.9%), and parainfluenza virus-1 (2.3%). Co-infections occurred in 29.4% (69/235) of infected patients and rhinovirus was the most detected virus (27.5%). Children under 5 years were more likely to have one or more detectable virus associated with their ILI. In this age group, compared to those ≥5 years, the risk of detecting more than one virus was higher (OR = 1.9), as was the risk of detecting of RSV (OR = 10.1) and adenovirus (OR = 4.7). While rhinovirus and adenovirus infections occurred year round, RSV, influenza virus A and coronavirus OC43 had defined period of circulation. CONCLUSIONS: In our study, we found that respiratory viruses play an important role in ILIs in the Malagasy community, particularly in children under 5 years old. These data provide a better understanding of the viral etiology of outpatients with ILI and describe for the first time importance of these viruses in different age group and their period of circulation.",2011 Mar 3,"['Razanajatovo, Norosoa Harline', 'Richard, Vincent', 'Hoffmann, Jonathan', 'Reynes, Jean-Marc', 'Razafitrimo, Girard Marcellin', 'Randremanana, Rindra Vatosoa', 'Heraud, Jean-Michel']",PLoS One,,,True
a040109f4ae97738c7940d711a60f07f573b9754,PMC,H9N2 influenza virus acquires intravenous pathogenicity on the introduction of a pair of di-basic amino acid residues at the cleavage site of the hemagglutinin and consecutive passages in chickens,http://dx.doi.org/10.1186/1743-422X-8-64,PMC3048564,21310053,CC BY,"BACKGROUND: Outbreaks of avian influenza (AI) caused by infection with low pathogenic H9N2 viruses have occurred in poultry, resulting in serious economic losses in Asia and the Middle East. It has been difficult to eradicate the H9N2 virus because of its low pathogenicity, frequently causing in apparent infection. It is important for the control of AI to assess whether the H9N2 virus acquires pathogenicity as H5 and H7 viruses. In the present study, we investigated whether a non-pathogenic H9N2 virus, A/chicken/Yokohama/aq-55/2001 (Y55) (H9N2), acquires pathogenicity in chickens when a pair of di-basic amino acid residues is introduced at the cleavage site of its HA molecule. RESULTS: rgY55sub (H9N2), which had four basic amino acid residues at the HA cleavage site, replicated in MDCK cells in the absence of trypsin after six consecutive passages in the air sacs of chicks, and acquired intravenous pathogenicity to chicken after four additional passages. More than 75% of chickens inoculated intravenously with the passaged virus, rgY55sub-P10 (H9N2), died, indicating that it is pathogenic comparable to that of highly pathogenic avian influenza viruses (HPAIVs) defined by World Organization for Animal Health (OIE). The chickens inoculated with the virus via the intranasal route, however, survived without showing any clinical signs. On the other hand, an avirulent H5N1 strain, A/duck/Hokkaido/Vac-1/2004 (Vac1) (H5N1), acquired intranasal pathogenicity after a pair of di-basic amino acid residues was introduced into the cleavage site of the HA, followed by two passages by air sac inoculation in chicks. CONCLUSION: The present results demonstrate that an H9N2 virus has the potential to acquire intravenous pathogenicity in chickens although the morbidity via the nasal route of infection is lower than that of H5N1 HPAIV.",2011 Feb 10,"['Soda, Kosuke', 'Asakura, Shingo', 'Okamatsu, Masatoshi', 'Sakoda, Yoshihiro', 'kida, Hiroshi']",Virol J,,,True
cdb117ad4ac490f1e48e3738d5ccdaafe8916086,PMC,"A multicentre, randomised, double-blind, single-dose study assessing the efficacy of AMC/DCBA Warm lozenge or AMC/DCBA Cool lozenge in the relief of acute sore throat",http://dx.doi.org/10.1186/1471-2296-12-6,PMC3050701,21332976,CC BY,"BACKGROUND: Clinically proven over-the-counter (OTC) treatment options are becoming increasingly important in the self-management of acute sore throat. The aim of this study was to determine the analgesic and sensorial benefits of two different amylmetacresol/2,4-dichlorobenzyl alcohol (AMC/DCBA) throat lozenge formulation variants, AMC/DCBA Warm lozenge and AMC/DCBA Cool lozenge, compared with an unflavoured, non-medicated placebo lozenge in the relief of acute sore throat due to upper respiratory tract infections. METHODS: In this multicentre, randomised, double-blind, single-dose study, 225 adult patients with acute sore throat were randomly assigned to receive either one AMC/DCBA Warm lozenge (n = 77), one AMC/DCBA Cool lozenge (n = 74) or one unflavoured, non-medicated lozenge (matched for size, shape and demulcency; n = 74). After baseline assessments, patients received their assigned lozenge and completed four rating assessments at 11 timepoints from 1 to 120 minutes post dose. Analgesic properties were assessed by comparing severity of throat soreness and sore throat relief ratings. Difficulty in swallowing, throat numbness, functional, sensorial and emotional benefits were also assessed. RESULTS: Both the AMC/DCBA Warm and AMC/DCBA Cool lozenge induced significant analgesic, functional, sensorial and emotional effects compared with the unflavoured, non-medicated lozenge. Sore throat relief, improvements in throat soreness and difficulty in swallowing, and throat numbness were observed as early as 1-5 minutes, and lasted up to 2 hours post dose. Sensorial benefits of warming and cooling associated with the AMC/DCBA Warm and AMC/DCBA Cool lozenge, respectively, were experienced soon after first dose, and in the case of the latter, it lasted long after the lozenge had dissolved. Emotional benefits of feeling better, happier, less distracted and less frustrated were reported in those taking either of the AMC/DCBA throat lozenge variants, with no differences in adverse events compared with the unflavoured, non-medicated lozenge. CONCLUSIONS: AMC/DCBA Warm and AMC/DCBA Cool lozenges are well-tolerated and effective OTC treatment options, offering functional, sensorial and emotional benefits to patients with acute sore throat, over and above that of the rapid efficacy effects provided. TRIAL REGISTRATION: ISRCTN: ISRCTN00003567",2011 Feb 18,"['Wade, Alan G', 'Morris, Christopher', 'Shephard, Adrian', 'Crawford, Gordon M', 'Goulder, Michael A']",BMC Fam Pract,,,True
7d92312dac3822da87cb86d3de9fe818e0ee2874,PMC,Peptide inhibition of human cytomegalovirus infection,http://dx.doi.org/10.1186/1743-422X-8-76,PMC3050824,21342525,CC BY,"BACKGROUND: Human cytomegalovirus (HCMV) is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV)- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB), a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. RESULTS: Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS), several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF) were infected with the Towne-GFP strain of HCMV (0.5 MOI), preincubated with peptides at a range of concentrations (78 nm to 100 μM), and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100 μM and 50 μM, respectively, and 60% at a concentration of 2.5 μM. While peptides 264-291 and 297-315, individually failed to inhibit viral infection, when combined, they showed 67% inhibition of HCMV infection at a concentration of 0.125 μM each. CONCLUSIONS: Peptides designed to target putative fusogenic domains of gB provide a basis for the development of novel therapeutics that prevent HCMV infection.",2011 Feb 22,"['Melnik, Lilia I', 'Garry, Robert F', 'Morris, Cindy A']",Virol J,,,True
985a0071613514c5f07592dc4d94d8916c2052d0,PMC,Risk Factors of Streptococcus suis Infection in Vietnam. A Case-Control Study,http://dx.doi.org/10.1371/journal.pone.0017604,PMC3050921,21408132,CC BY,"BACKGROUND: Streptococcus suis infection, an emerging zoonosis, is an increasing public health problem across South East Asia and the most common cause of acute bacterial meningitis in adults in Vietnam. Little is known of the risk factors underlying the disease. METHODS AND FINDINGS: A case-control study with appropriate hospital and matched community controls for each patient was conducted between May 2006 and June 2009. Potential risk factors were assessed using a standardized questionnaire and investigation of throat and rectal S. suis carriage in cases, controls and their pigs, using real-time PCR and culture of swab samples. We recruited 101 cases of S. suis meningitis, 303 hospital controls and 300 community controls. By multivariate analysis, risk factors identified for S. suis infection as compared to either control group included eating “high risk” dishes, including such dishes as undercooked pig blood and pig intestine (OR(1) = 2.22; 95%CI = [1.15–4.28] and OR(2) = 4.44; 95%CI = [2.15–9.15]), occupations related to pigs (OR(1) = 3.84; 95%CI = [1.32–11.11] and OR(2) = 5.52; 95%CI = [1.49–20.39]), and exposures to pigs or pork in the presence of skin injuries (OR(1) = 7.48; 95%CI = [1.97–28.44] and OR(2) = 15.96; 95%CI = [2.97–85.72]). S. suis specific DNA was detected in rectal and throat swabs of 6 patients and was cultured from 2 rectal samples, but was not detected in such samples of 1522 healthy individuals or patients without S. suis infection. CONCLUSIONS: This case control study, the largest prospective epidemiological assessment of this disease, has identified the most important risk factors associated with S. suis bacterial meningitis to be eating ‘high risk’ dishes popular in parts of Asia, occupational exposure to pigs and pig products, and preparation of pork in the presence of skin lesions. These risk factors can be addressed in public health campaigns aimed at preventing S. suis infection.",2011 Mar 8,"['Ho, Dang Trung Nghia', 'Le, Thi Phuong Tu', 'Wolbers, Marcel', 'Cao, Quang Thai', 'Nguyen, Van Minh Hoang', 'Tran, Vu Thieu Nga', 'Le, Thi Phuong Thao', 'Nguyen, Hoan Phu', 'Tran, Thi Hong Chau', 'Dinh, Xuan Sinh', 'To, Song Diep', 'Hoang, Thi Thanh Hang', 'Hoang, Truong', 'Campbell, James', 'Nguyen, Van Vinh Chau', 'Nguyen, Tran Chinh', 'Nguyen, Van Dung', 'Ngo, Thi Hoa', 'Spratt, Brian G.', 'Tran, Tinh Hien', 'Farrar, Jeremy', 'Schultsz, Constance']",PLoS One,,,True
1686765b6847c2b132d0129be10f7263bac5973e,PMC,Experimental infection of hamsters with avian paramyxovirus serotypes 1 to 9,http://dx.doi.org/10.1186/1297-9716-42-38,PMC3052182,21345199,CC BY,"Avian paramyxoviruses (APMVs) are frequently isolated from domestic and wild birds throughout the world and are separated into nine serotypes (APMV-1 to -9). Only in the case of APMV-1, the infection of non-avian species has been investigated. The APMVs presently are being considered as human vaccine vectors. In this study, we evaluated the replication and pathogenicity of all nine APMV serotypes in hamsters. The hamsters were inoculated intranasally with each virus and monitored for clinical disease, pathology, histopathology, virus replication, and seroconversion. On the basis of one or more of these criteria, each of the APMV serotypes was found to replicate in hamsters. The APMVs produced mild or inapparent clinical signs in hamsters except for APMV-9, which produced moderate disease. Gross lesions were observed over the pulmonary surface of hamsters infected with APMV-2 & -3, which showed petechial and ecchymotic hemorrhages, respectively. Replication of all of the APMVs except APMV-5 was confirmed in the nasal turbinates and lungs, indicating a tropism for the respiratory tract. Histologically, the infection resulted in lung lesions consistent with bronchointerstitial pneumonia of varying severity and nasal turbinates with blunting or loss of cilia of the epithelium lining the nasal septa. The majority of APMV-infected hamsters exhibited transient histological lesions that self resolved by 14 days post infection (dpi). All of the hamsters infected with the APMVs produced serotype-specific HI or neutralizing antibodies, confirming virus replication. Taken together, these results demonstrate that all nine known APMV serotypes are capable of replicating in hamsters with minimal disease and pathology.",2011 Feb 23,"['Samuel, Arthur S', 'Subbiah, Madhuri', 'Shive, Heather', 'Collins, Peter L', 'Samal, Siba K']",Vet Res,,,True
ae40184ce67c93d60f2d5d00f451b00017af16cb,PMC,Estimation of transmission parameters of a fluoroquinolone-resistant Escherichia coli strain between pigs in experimental conditions,http://dx.doi.org/10.1186/1297-9716-42-44,PMC3053234,21366902,CC BY,"Antimicrobial resistance is of primary importance regarding public and animal health issues. Persistence and spread of resistant strains within a population contribute to the maintenance of a reservoir and lead to treatment failure. An experimental trial was carried out to study the horizontal transmission of a fluoroquinolone-resistant Escherichia coli strain from inoculated to naïve pigs. All naïve contact pigs had positive counts of fluoroquinolone-resistant E. coli after only two days of contact. Moreover, re-infections of inoculated pigs caused by newly contaminated animals were suspected. A maximum likelihood method, based on a susceptible-infectious-susceptible (SIS) model, was used to determine the transmission parameters. Two transmission levels were identified depending on the quantity of bacteria shed by infected individuals: (i) low-shedders with bacterial counts of resistant E. coli in the faeces between 5*10(3 )and 10(6 )CFU/g (β(L )= 0.41 [0.27; 0.62]), (ii) high shedders with bacterial counts above 10(6 )CFU/g (β(H )= 0.98 [0.59; 1.62]). Hence, transmission between animals could be pivotal in explaining the persistence of resistant bacteria within pig herds.",2011 Mar 2,"['Andraud, Mathieu', 'Rose, Nicolas', 'Laurentie, Michel', 'Sanders, Pascal', 'Le Roux, Aurélie', 'Cariolet, Roland', 'Chauvin, Claire', 'Jouy, Eric']",Vet Res,,,True
9791652bce8752738f1bfb75305fd5faa6e30374,PMC,Factors Affecting Intention to Receive and Self-Reported Receipt of 2009 Pandemic (H1N1) Vaccine in Hong Kong: A Longitudinal Study,http://dx.doi.org/10.1371/journal.pone.0017713,PMC3055876,21412418,CC BY,"BACKGROUND: Vaccination was a core component for mitigating the 2009 influenza pandemic (pH1N1). However, a vaccination program's efficacy largely depends on population compliance. We examined general population decision-making for pH1N1 vaccination using a modified Theory of Planned Behaviour (TBP). METHODOLOGY: We conducted a longitudinal study, collecting data before and after the introduction of pH1N1 vaccine in Hong Kong. Structural equation modeling (SEM) tested if a modified TPB had explanatory utility for vaccine uptake among adults. PRINCIPAL FINDINGS: Among 896 subjects who completed both the baseline and the follow-up surveys, 7% (67/896) reported being “likely/very likely/certain” to be vaccinated (intent) but two months later only 0.8% (7/896) reported having received pH1N1 vaccination. Perception of low risk from pH1N1 (60%) and concerns regarding adverse effects of the vaccine (37%) were primary justifications for avoiding pH1N1 vaccination. Greater perceived vaccine benefits (β = 0.15), less concerns regarding vaccine side-effects (β = −0.20), greater adherence to social norms of vaccination (β = 0.39), anticipated higher regret if not vaccinated (β = 0.47), perceived higher self-efficacy for vaccination (β = 0.12) and history of seasonal influenza vaccination (β = 0.12) were associated with higher intention to receive the pH1N1 vaccine, which in turn predicted self-reported vaccination uptake (β = 0.30). Social norm (β = 0.70), anticipated regret (β = 0.19) and vaccination intention (β = 0.31) were positively associated with, and accounted for 70% of variance in vaccination planning, which, in turn subsequently predicted self-reported vaccination uptake (β = 0.36) accounting for 36% of variance in reported vaccination behaviour. CONCLUSIONS/SIGNIFICANCE: Perceived low risk from pH1N1 and perceived high risk from pH1N1 vaccine inhibited pH1N1 vaccine uptake. Both the TPB and the additional components contributed to intended vaccination uptake but social norms and anticipated regret predominantly associated with vaccination intention and planning. Vaccination planning is a more significant proximal determinant of uptake of pH1N1 vaccine than is intention. Intention alone is an unreliable predictor of future vaccine uptake.",2011 Mar 11,"['Liao, Qiuyan', 'Cowling, Benjamin J.', 'Lam, Wendy Wing Tak', 'Fielding, Richard']",PLoS One,,,True
c24af6314214e7d2ef8b04419efccd6f7f900858,PMC,Epithelial Cell Stretching and Luminal Acidification Lead to a Retarded Development of Stria Vascularis and Deafness in Mice Lacking Pendrin,http://dx.doi.org/10.1371/journal.pone.0017949,PMC3056798,21423764,CC BY,"Loss-of-function mutations of SLC26A4/pendrin are among the most prevalent causes of deafness. Deafness and vestibular dysfunction in the corresponding mouse model, Slc26a4(−/−), are associated with an enlargement and acidification of the membranous labyrinth. Here we relate the onset of expression of the HCO(3) (−) transporter pendrin to the luminal pH and to enlargement-associated epithelial cell stretching. We determined expression with immunocytochemistry, cell stretching by digital morphometry and pH with double-barreled ion-selective electrodes. Pendrin was first expressed in the endolymphatic sac at embryonic day (E) 11.5, in the cochlear hook-region at E13.5, in the utricle and saccule at E14.5, in ampullae at E16.5, and in the upper turn of the cochlea at E17.5. Epithelial cell stretching in Slc26a4(−/−) mice began at E14.5. pH changes occurred first in the cochlea at E15.5 and in the endolymphatic sac at E17.5. At postnatal day 2, stria vascularis, outer sulcus and Reissner's membrane epithelial cells, and utricular and saccular transitional cells were stretched, whereas sensory cells in the cochlea, utricle and saccule did not differ between Slc26a4(+/−) and Slc26a4(−/−) mice. Structural development of stria vascularis, including vascularization, was retarded in Slc26a4(−/−) mice. In conclusion, the data demonstrate that the enlargement and stretching of non-sensory epithelial cells precedes luminal acidification in the cochlea and the endolymphatic sac. Stretching and luminal acidification may alter cell-to-cell communication and lead to the observed retarded development of stria vascularis, which may be an important step on the path to deafness in Slc26a4(−/−) mice, and possibly in humans, lacking functional pendrin expression.",2011 Mar 14,"['Kim, Hyoung-Mi', 'Wangemann, Philine']",PLoS One,,,True
bb3716d66667c66f6f79b37c765388cd334f2cad,PMC,Tylosema esculentum (Marama) Tuber and Bean Extracts Are Strong Antiviral Agents against Rotavirus Infection,http://dx.doi.org/10.1155/2011/284795,PMC3057194,21423688,CC BY,"Tylosema esculentum (marama) beans and tubers are used as food, and traditional medicine against diarrhoea in Southern Africa. Rotaviruses (RVs) are a major cause of diarrhoea among infants, young children, immunocompromised people, and domesticated animals. Our work is first to determine anti-RV activity of marama bean and tuber ethanol and water extracts; in this case on intestinal enterocyte cells of human infant (H4), adult pig (CLAB) and adult bovine (CIEB) origin. Marama cotyledon ethanolic extract (MCE) and cotyledon water extract (MCW) without RV were not cytotoxic to all cells tested, while seed coat and tuber extracts showed variable levels of cytotoxicity. Marama cotyledon ethanolic and water extracts (MCE and MCW, resp.) (≥0.1 mg/mL), seed coat extract (MSCE) and seed coat water extract (MSCW) (0.01 to 0.001 mg/mL), especially ethanolic, significantly increased cell survival and enhanced survival to cytopathic effects of RV by at least 100% after in vitro co- and pre-incubation treatments. All marama extracts used significantly enhanced nitric oxide release from H4 cells and enhanced TER (Ω/cm(2)) of enterocyte barriers after coincubation with RV. Marama cotyledon and seed coat extracts inhibited virion infectivity possibly through interference with replication due to accumulation of nitric oxide. Marama extracts are therefore promising microbicides against RV.",2011 Feb 20,"['Chingwaru, Walter', 'Majinda, Runner T.', 'Yeboah, Sam O.', 'Jackson, Jose C.', 'Kapewangolo, Petrina T.', 'Kandawa-Schulz, Martha', 'Cencic, Avrelija']",Evid Based Complement Alternat Med,,,True
f3b46e7e8f58799207cc44515f859c1daf5e4dfc,PMC,Exhaled breath condensate sampling is not a new method for detection of respiratory viruses,http://dx.doi.org/10.1186/1743-422X-8-98,PMC3059288,21375748,CC BY,"BACKGROUND: Exhaled breath condensate (EBC) sampling has been considered an inventive and novel method for the isolation of respiratory viruses. METHODS: In our study, 102 volunteers experiencing upper airway infection were recruited over the winter and early spring of 2008/2009 and the first half of the winter of 2009/2010. Ninety-nine EBCs were successfully obtained and screened for 14 commonly circulating respiratory viruses. To investigate the efficiency of virus isolation from EBC, a nasal swab was taken in parallel from a subset of volunteers. The combined use of the ECoVent device with the RTube™ allowed the registration of the exhaled volume and breathing frequency during collection. In this way, the number of exhaled viral particles per liter air or per minute can theoretically be estimated. RESULTS: Viral screening resulted in the detection of 4 different viruses in EBC and/or nasal swabs: Rhinovirus, Human Respiratory Syncytial Virus B, Influenza A and Influenza B. Rhinovirus was detected in 6 EBCs and 1 EBC was Influenza B positive. We report a viral detection rate of 7% for the EBCs, which is much lower than the detection rate of 46.8% observed using nasal swabs. CONCLUSION: Although very promising, EBC collection using the RTube™ is not reliable for diagnosis of respiratory infections.",2011 Mar 4,"['Houspie, Lieselot', 'De Coster, Sarah', 'Keyaerts, Els', 'Narongsack, Phouthalack', 'De Roy, Rikka', 'Talboom, Ive', 'Sisk, Maura', 'Maes, Piet', 'Verbeeck, Jannick', 'Van Ranst, Marc']",Virol J,,,True
c44a9d064faca56bd284971828e4db13e656365c,PMC,Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies,http://dx.doi.org/10.1371/journal.pcbi.1002015,PMC3060167,21483468,CC BY,"Infectious disease treatments, both pharmaceutical and vaccine, face three universal challenges: the difficulty of targeting treatments to high-risk ‘superspreader’ populations who drive the great majority of disease spread, behavioral barriers in the host population (such as poor compliance and risk disinhibition), and the evolution of pathogen resistance. Here, we describe a proposed intervention that would overcome these challenges by capitalizing upon Therapeutic Interfering Particles (TIPs) that are engineered to replicate conditionally in the presence of the pathogen and spread between individuals — analogous to ‘transmissible immunization’ that occurs with live-attenuated vaccines (but without the potential for reversion to virulence). Building on analyses of HIV field data from sub-Saharan Africa, we construct a multi-scale model, beginning at the single-cell level, to predict the effect of TIPs on individual patient viral loads and ultimately population-level disease prevalence. Our results show that a TIP, engineered with properties based on a recent HIV gene-therapy trial, could stably lower HIV/AIDS prevalence by ∼30-fold within 50 years and could complement current therapies. In contrast, optimistic antiretroviral therapy or vaccination campaigns alone could only lower HIV/AIDS prevalence by <2-fold over 50 years. The TIP's efficacy arises from its exploitation of the same risk factors as the pathogen, allowing it to autonomously penetrate superspreader populations, maintain efficacy despite behavioral disinhibition, and limit viral resistance. While demonstrated here for HIV, the TIP concept could apply broadly to many viral infectious diseases and would represent a new paradigm for disease control, away from pathogen eradication but toward robust disease suppression.",2011 Mar 17,"['Metzger, Vincent T.', 'Lloyd-Smith, James O.', 'Weinberger, Leor S.']",PLoS Comput Biol,,,True
40400327bbd828910ba0e013d9de71c012b4d4e1,PMC,Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies,http://dx.doi.org/10.1371/journal.pcbi.1002015,PMC3060167,21483468,CC BY,"Infectious disease treatments, both pharmaceutical and vaccine, face three universal challenges: the difficulty of targeting treatments to high-risk ‘superspreader’ populations who drive the great majority of disease spread, behavioral barriers in the host population (such as poor compliance and risk disinhibition), and the evolution of pathogen resistance. Here, we describe a proposed intervention that would overcome these challenges by capitalizing upon Therapeutic Interfering Particles (TIPs) that are engineered to replicate conditionally in the presence of the pathogen and spread between individuals — analogous to ‘transmissible immunization’ that occurs with live-attenuated vaccines (but without the potential for reversion to virulence). Building on analyses of HIV field data from sub-Saharan Africa, we construct a multi-scale model, beginning at the single-cell level, to predict the effect of TIPs on individual patient viral loads and ultimately population-level disease prevalence. Our results show that a TIP, engineered with properties based on a recent HIV gene-therapy trial, could stably lower HIV/AIDS prevalence by ∼30-fold within 50 years and could complement current therapies. In contrast, optimistic antiretroviral therapy or vaccination campaigns alone could only lower HIV/AIDS prevalence by <2-fold over 50 years. The TIP's efficacy arises from its exploitation of the same risk factors as the pathogen, allowing it to autonomously penetrate superspreader populations, maintain efficacy despite behavioral disinhibition, and limit viral resistance. While demonstrated here for HIV, the TIP concept could apply broadly to many viral infectious diseases and would represent a new paradigm for disease control, away from pathogen eradication but toward robust disease suppression.",2011 Mar 17,"['Metzger, Vincent T.', 'Lloyd-Smith, James O.', 'Weinberger, Leor S.']",PLoS Comput Biol,,,True
18fa3d1a5503e1943ce8e657416f9da8fe2cb475,PMC,Proteomic analysis of chicken embryonic trachea and kidney tissues after infection in ovo by avian infectious bronchitis coronavirus,http://dx.doi.org/10.1186/1477-5956-9-11,PMC3060854,21385394,CC BY,"BACKGROUND: Avian infectious bronchitis (IB) is one of the most serious diseases of economic importance in chickens; it is caused by the avian infectious coronavirus (IBV). Information remains limited about the comparative protein expression profiles of chicken embryonic tissues in response to IBV infection in ovo. In this study, we analyzed the changes of protein expression in trachea and kidney tissues from chicken embryos, following IBV infection in ovo, using two-dimensional gel electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF-TOF MS). RESULTS: 17 differentially expressed proteins from tracheal tissues and 19 differentially expressed proteins from kidney tissues were identified. These proteins mostly related to the cytoskeleton, binding of calcium ions, the stress response, anti-oxidative, and macromolecular metabolism. Some of these altered proteins were confirmed further at the mRNA level using real-time RT-PCR. Moreover, western blotting analysis further confirmed the changes of annexin A5 and HSPB1 during IBV infection. CONCLUSIONS: To the best of our knowledge, we have performed the first analysis of the proteomic changes in chicken embryonic trachea and kidney tissues during IBV infection in ovo. The data obtained should facilitate a better understanding of the pathogenesis of IBV infection.",2011 Mar 8,"['Cao, Zhongzan', 'Han, Zongxi', 'Shao, Yuhao', 'Geng, Heyuan', 'Kong, Xiangang', 'Liu, Shengwang']",Proteome Sci,,,True
6efeb37a50a81c7769a49bcf030e54b148bd1fbd,PMC,Screening of Random Peptide Library of Hemagglutinin from Pandemic 2009 A(H1N1) Influenza Virus Reveals Unexpected Antigenically Important Regions,http://dx.doi.org/10.1371/journal.pone.0018016,PMC3060926,21437206,CC BY,"The antigenic structure of the membrane protein hemagglutinin (HA) from the 2009 A(H1N1) influenza virus was dissected with a high-throughput screening method using complex antisera. The approach involves generating yeast cell libraries displaying a pool of random peptides of controllable lengths on the cell surface, followed by one round of fluorescence-activated cell sorting (FACS) against antisera from mouse, goat and human, respectively. The amino acid residue frequency appearing in the antigenic peptides at both the primary sequence and structural level was determined and used to identify “hot spots” or antigenically important regions. Unexpectedly, different antigenic structures were seen for different antisera. Moreover, five antigenic regions were identified, of which all but one are located in the conserved HA stem region that is responsible for membrane fusion. Our findings are corroborated by several recent studies on cross-neutralizing H1 subtype antibodies that recognize the HA stem region. The antigenic peptides identified may provide clues for creating peptide vaccines with better accessibility to memory B cells and better induction of cross-neutralizing antibodies than the whole HA protein. The scheme used in this study enables a direct mapping of the antigenic regions of viral proteins recognized by antisera, and may be useful for dissecting the antigenic structures of other viral proteins.",2011 Mar 18,"['Xu, Wanghui', 'Han, Lu', 'Lin, Zhanglin']",PLoS One,,,True
d88b1e3e4d603dde6f344785e2371292e56f73a0,PMC,Proteomic analysis of swine serum following highly virulent classical swine fever virus infection,http://dx.doi.org/10.1186/1743-422X-8-107,PMC3061939,21385403,CC BY,"BACKGROUND: Classical swine fever virus (CSFV) belongs to the genus Pestivirus within the family Flaviviridae. Virulent strains of classical swine fever virus (CSFV) cause severe disease in pigs characterized by immunosuppression, thrombocytopenia and disseminated intravascular coagulation, which causes significant economic losses to the pig industry worldwide. METHODS: To reveal proteomic changes in swine serum during the acute stage of lethal CSFV infection, 5 of 10 pigs were inoculated with the virulent CSFV Shimen strain, the remainder serving as uninfected controls. A serum sample was taken at 3 days post-infection from each swine, at a stage when there were no clinical symptoms other than increased rectal temperatures (≥40°C). The samples were treated to remove serum albumin and immunoglobulin (IgG), and then subjected to two-dimension differential gel electrophoresis. RESULTS: Quantitative intensity analysis revealed 17 protein spots showing at least 1.5-fold quantitative alteration in expression. Ten spots were successfully identified by MALDI-TOF MS or LTQ MS. Expression of 4 proteins was increased and 6 decreased in CSFV-infected pigs. Functions of these proteins included blood coagulation, anti-inflammatory activity and angiogenesis. CONCLUSION: These proteins with altered expression may have important implications in the pathogenesis of classical swine fever and provide a clue for identification of biomarkers for classical swine fever early diagnosis.",2011 Mar 8,"['Sun, Jin-fu', 'Shi, Zi-xue', 'Guo, Huan-cheng', 'Li, Su', 'Tu, Chang-chun']",Virol J,,,True
62b348dd9761ec78af4d53ad162a747cd300edce,PMC,Vascular disrupting agent DMXAA enhances the antitumor effects generated by therapeutic HPV DNA vaccines,http://dx.doi.org/10.1186/1423-0127-18-21,PMC3062584,21385449,CC BY,"Antigen-specific immunotherapy using DNA vaccines has emerged as an attractive approach for the control of tumors. Another novel cancer therapy involves the employment of the vascular disrupting agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA). In the current study, we aimed to test the combination of DMXAA treatment with human papillomavirus type 16 (HPV-16) E7 DNA vaccination to enhance the antitumor effects and E7-specific CD8+ T cell immune responses in treated mice. We determined that treatment with DMXAA generates significant therapeutic effects against TC-1 tumors but does not enhance the antigen-specific immune responses in tumor bearing mice. We then found that combination of DMXAA treatment with E7 DNA vaccination generates potent antitumor effects and E7-specific CD8+ T cell immune responses in the splenocytes of tumor bearing mice. Furthermore, the DMXAA-mediated enhancement or suppression of E7-specific CD8+ T cell immune responses generated by CRT/E7 DNA vaccination was found to be dependent on the time of administration of DMXAA and was also applicable to other antigen-specific vaccines. In addition, we determined that inducible nitric oxide synthase (iNOS) plays a role in the immune suppression caused by DMXAA administration before DNA vaccination. Our study has significant implications for future clinical translation.",2011 Mar 8,"['Peng, Shiwen', 'Monie, Archana', 'Pang, Xiaowu', 'Hung, Chien-Fu', 'Wu, T-C']",J Biomed Sci,,,True
42f17b849628fb1db7c74cc15899bf9b9c59de93,PMC,Networks and the Epidemiology of Infectious Disease,http://dx.doi.org/10.1155/2011/284909,PMC3062985,21437001,CC BY,"The science of networks has revolutionised research into the dynamics of interacting elements. It could be argued that epidemiology in particular has embraced the potential of network theory more than any other discipline. Here we review the growing body of research concerning the spread of infectious diseases on networks, focusing on the interplay between network theory and epidemiology. The review is split into four main sections, which examine: the types of network relevant to epidemiology; the multitude of ways these networks can be characterised; the statistical methods that can be applied to infer the epidemiological parameters on a realised network; and finally simulation and analytical methods to determine epidemic dynamics on a given network. Given the breadth of areas covered and the ever-expanding number of publications, a comprehensive review of all work is impossible. Instead, we provide a personalised overview into the areas of network epidemiology that have seen the greatest progress in recent years or have the greatest potential to provide novel insights. As such, considerable importance is placed on analytical approaches and statistical methods which are both rapidly expanding fields. Throughout this review we restrict our attention to epidemiological issues.",2011 Mar 16,"['Danon, Leon', 'Ford, Ashley P.', 'House, Thomas', 'Jewell, Chris P.', 'Keeling, Matt J.', 'Roberts, Gareth O.', 'Ross, Joshua V.', 'Vernon, Matthew C.']",Interdiscip Perspect Infect Dis,,,True
e5f66769b3cbcb6b378257a7c83acdb1793a6803,PMC,Viral Encephalomyelitis,http://dx.doi.org/10.1371/journal.ppat.1002004,PMC3063766,21455493,CC BY,,2011 Mar 24,"Griffin, Diane E.",PLoS Pathog,,,True
c05da515acecfc66d0b0b7a46a51e557cb9bb08d,PMC,Assessing the In Vitro Fitness of an Oseltamivir-Resistant Seasonal A/H1N1 Influenza Strain Using a Mathematical Model,http://dx.doi.org/10.1371/journal.pone.0014767,PMC3063785,21455300,CC BY,"In 2007, the A/Brisbane/59/2007 (H1N1) seasonal influenza virus strain acquired the oseltamivir-resistance mutation H275Y in its neuraminidase (NA) gene. Although previous studies had demonstrated that this mutation impaired the replication capacity of the influenza virus in vitro and in vivo, the A/Brisbane/59/2007 H275Y oseltamivir-resistant mutant completely out-competed the wild-type (WT) strain and was, in the 2008–2009 influenza season, the primary A/H1N1 circulating strain. Using a combination of plaque and viral yield assays, and a simple mathematical model, approximate values were extracted for two basic viral kinetics parameters of the in vitro infection. In the ST6GalI-MDCK cell line, the latent infection period (i.e., the time for a newly infected cell to start releasing virions) was found to be 1–3 h for the WT strain and more than 7 h for the H275Y mutant. The infecting time (i.e., the time for a single infectious cell to cause the infection of another one) was between 30 and 80 min for the WT, and less than 5 min for the H275Y mutant. Single-cycle viral yield experiments have provided qualitative confirmation of these findings. These results, though preliminary, suggest that the increased fitness success of the A/Brisbane/59/2007 H275Y mutant may be due to increased infectivity compensating for an impaired or delayed viral release, and are consistent with recent evidence for the mechanistic origins of fitness reduction and recovery in NA expression. The method applied here can reconcile seemingly contradictory results from the plaque and yield assays as two complementary views of replication kinetics, with both required to fully capture a strain's fitness.",2011 Mar 24,"['Holder, Benjamin P.', 'Simon, Philippe', 'Liao, Laura E.', 'Abed, Yacine', 'Bouhy, Xavier', 'Beauchemin, Catherine A. A.', 'Boivin, Guy']",PLoS One,,,True
73ae7423efc653849fa7d2b6b2770164dd02b2c1,PMC,"Viral Etiologies of Acute Respiratory Infections among Hospitalized Vietnamese Children in Ho Chi Minh City, 2004–2008",http://dx.doi.org/10.1371/journal.pone.0018176,PMC3063798,21455313,CC BY,"BACKGROUND: The dominant viral etiologies responsible for acute respiratory infections (ARIs) are poorly understood, particularly among hospitalized children in resource-limited tropical countries where morbidity and mortality caused by ARIs are highest. Improved etiological insight is needed to improve clinical management and prevention. OBJECTIVES: We conducted a three-year prospective descriptive study of severe respiratory illness among children from 2 months to 13 years of age within the largest referral hospital for infectious diseases in southern Vietnam. METHODS: Molecular detection for 15 viral species and subtypes was performed on three types of respiratory specimens (nose, throat swabs and nasopharyngeal aspirates) using a multiplex RT-PCR kit (Seeplex™ RV detection, Seegene) and additional monoplex real-time RT-PCRs. RESULTS: A total of 309 children were enrolled from November 2004 to January 2008. Viruses were identified in 72% (222/309) of cases, including respiratory syncytial virus (24%), influenza virus A and B (17%), human bocavirus (16%), enterovirus (9%), human coronavirus (8%), human metapneumovirus (7%), parainfluenza virus 1–3 (6%), adenovirus (5%), and human rhinovirus A (4%). Co-infections with multiple viruses were detected in 20% (62/309) of patients. When combined, diagnostic yields in nose and throat swabs were similar to nasopharyngeal aspirates. CONCLUSION: Similar to other parts in the world, RSV and influenza were the predominant viral pathogens detected in Vietnamese hospitalized children. Combined nasal and throat swabs are the specimens of choice for sensitive molecular detection of a broad panel of viral agents. Further research is required to better understand the clinical significance of single versus multiple viral coinfections and to address the role of bacterial (co-)infections involved in severe respiratory illness.",2011 Mar 24,"['Do, Anh Ha Lien', 'van Doorn, H. Rogier', 'Nghiem, My Ngoc', 'Bryant, Juliet E.', 'Hoang, Thanh Hang thi', 'Do, Quang Ha', 'Le Van, Tan', 'Tran, Tan Thanh', 'Wills, Bridget', 'van Nguyen, Vinh Chau', 'Vo, Minh Hien', 'Vo, Cong Khanh', 'Nguyen, Minh Dung', 'Farrar, Jeremy', 'Tran, Tinh Hien', 'de Jong, Menno D.']",PLoS One,,,True
048b240dcabbd623a6cda8c4236ea50d7961315c,PMC,The Role of Thailand in the International Trade in CITES-Listed Live Reptiles and Amphibians,http://dx.doi.org/10.1371/journal.pone.0017825,PMC3064566,21464976,CC BY,"BACKGROUND: International wildlife trade is one of the leading threats to biodiversity conservation. The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) is the most important initiative to monitor and regulate the international trade of wildlife but its credibility is dependent on the quality of the trade data. We report on the performance of CITES reporting by focussing on the commercial trade in non-native reptiles and amphibians into Thailand as to illustrate trends, species composition and numbers of wild-caught vs. captive-bred specimens. METHODOLOGY/PRINCIPAL FINDINGS: Based on data in the WCMC-CITES trade database, we establish that a total of 75,594 individuals of 169 species of reptiles and amphibians (including 27 globally threatened species) were imported into Thailand in 1990–2007. The majority of individuals (59,895, 79%) were listed as captive-bred and a smaller number (15,699, 21%) as wild-caught. In the 1990s small numbers of individuals of a few species were imported into Thailand, but in 2003 both volumes and species diversity increased rapidly. The proportion of captive-bred animals differed greatly between years (from 0 to >80%). Wild-caught individuals were mainly sourced from African countries, and captive-bred individuals from Asian countries (including from non-CITES Parties). There were significant discrepancies between exports and imports. Thailand reports the import of >10,000 individuals (51 species) originating from Kazakhstan, but Kazakhstan reports no exports of these species. Similar discrepancies, involving smaller numbers (>100 individuals of 9 species), can be seen in the import of reptiles into Thailand via Macao. CONCLUSION/SIGNIFICANCE: While there has been an increase in imports of amphibian and reptiles into Thailand, erratic patterns in proportions of captive-bred specimens and volumes suggests either capricious markets or errors in reporting. Large discrepancies with respect to origin point to misreporting or possible violations of the rules and intentions of CITES.",2011 Mar 25,"['Nijman, Vincent', 'Shepherd, Chris R.']",PLoS One,,,True
6cc30d377f0bd9004378ef98ef2b7c145a79711e,PMC,"Genomic Signatures of Strain Selection and Enhancement in Bacillus atrophaeus var. globigii, a Historical Biowarfare Simulant",http://dx.doi.org/10.1371/journal.pone.0017836,PMC3064580,21464989,CC0,"BACKGROUND: Despite the decades-long use of Bacillus atrophaeus var. globigii (BG) as a simulant for biological warfare (BW) agents, knowledge of its genome composition is limited. Furthermore, the ability to differentiate signatures of deliberate adaptation and selection from natural variation is lacking for most bacterial agents. We characterized a lineage of BGwith a long history of use as a simulant for BW operations, focusing on classical bacteriological markers, metabolic profiling and whole-genome shotgun sequencing (WGS). RESULTS: Archival strains and two “present day” type strains were compared to simulant strains on different laboratory media. Several of the samples produced multiple colony morphotypes that differed from that of an archival isolate. To trace the microevolutionary history of these isolates, we obtained WGS data for several archival and present-day strains and morphotypes. Bacillus-wide phylogenetic analysis identified B. subtilis as the nearest neighbor to B. atrophaeus. The genome of B. atrophaeus is, on average, 86% identical to B. subtilis on the nucleotide level. WGS of variants revealed that several strains were mixed but highly related populations and uncovered a progressive accumulation of mutations among the “military” isolates. Metabolic profiling and microscopic examination of bacterial cultures revealed enhanced growth of “military” isolates on lactate-containing media, and showed that the “military” strains exhibited a hypersporulating phenotype. CONCLUSIONS: Our analysis revealed the genomic and phenotypic signatures of strain adaptation and deliberate selection for traits that were desirable in a simulant organism. Together, these results demonstrate the power of whole-genome and modern systems-level approaches to characterize microbial lineages to develop and validate forensic markers for strain discrimination and reveal signatures of deliberate adaptation.",2011 Mar 25,"['Gibbons, Henry S.', 'Broomall, Stacey M.', 'McNew, Lauren A.', 'Daligault, Hajnalka', 'Chapman, Carol', 'Bruce, David', 'Karavis, Mark', 'Krepps, Michael', 'McGregor, Paul A.', 'Hong, Charles', 'Park, Kyong H.', 'Akmal, Arya', 'Feldman, Andrew', 'Lin, Jeffrey S.', 'Chang, Wenling E.', 'Higgs, Brandon W.', 'Demirev, Plamen', 'Lindquist, John', 'Liem, Alvin', 'Fochler, Ed', 'Read, Timothy D.', 'Tapia, Roxanne', 'Johnson, Shannon', 'Bishop-Lilly, Kimberly A.', 'Detter, Chris', 'Han, Cliff', 'Sozhamannan, Shanmuga', 'Rosenzweig, C. Nicole', 'Skowronski, Evan W.']",PLoS One,,,True
9d4ce1e58828bc78c7c83f40c14765df96feb277,PMC,Differential Induction of Functional IgG Using the Plasmodium falciparum Placental Malaria Vaccine Candidate VAR2CSA,http://dx.doi.org/10.1371/journal.pone.0017942,PMC3064590,21464946,CC BY,"BACKGROUND: In Plasmodium falciparum malaria endemic areas placental malaria (PM) is an important complication of malaria. The recurrence of malaria in primigravidae women irrespective of acquired protection during childhood is caused by the interaction between the parasite-expressed VAR2CSA antigen and chondroitin sulfate A (CSA) in the placental intervillous space and lack of protective antibodies. PM impairs fetal development mainly by excessive inflammation processes. After infections during pregnancy women acquire immunity to PM conferred by antibodies against VAR2CSA. Ideally, a vaccine against PM will induce antibody-mediated immune responses that block the adhesion of infected erythrocytes (IE) in the placenta. PRINCIPAL FINDINGS: We have previously shown that antibodies raised in rat against individual domains of VAR2CSA can block IE binding to CSA. In this study we have immunized mice, rats and rabbits with each individual domain and the full-length protein corresponding to the FCR3 VAR2CSA variant. We found there is an inherently higher immunogenicity of C-terminal domains compared to N-terminally located domains. This was irrespective of whether antibodies were induced against single domains or the full-length protein. Species-specific antibody responses were also found, these were mainly directed against single domains and not the full-length VAR2CSA protein. CONCLUSIONS/SIGNIFICANCE: Binding inhibitory antibodies appeared to be against conformational B-cell epitopes. Non-binding inhibitory antibodies reacted highly against the C-terminal end of the VAR2CSA molecule especially the highly polymorphic DBL6ε domain. Differential species-specific induction of antibody responses may allow for more direct analysis of functional versus non-functional B-cell epitopes.",2011 Mar 25,"['Pinto, Vera V.', 'Ditlev, Sisse B.', 'Jensen, Kamilla E.', 'Resende, Mafalda', 'Dahlbäck, Madeleine', 'Andersen, Gorm', 'Andersen, Pernille', 'Theander, Thor G.', 'Salanti, Ali', 'Nielsen, Morten A.']",PLoS One,,,True
c883fc2c4774529ce853012e339acf2aadc53454,PMC,Human rhinovirus infection in young African children with acute wheezing,http://dx.doi.org/10.1186/1471-2334-11-65,PMC3065410,21401965,CC BY,"BACKGROUND: Infections caused by human rhinoviruses (HRVs) are important triggers of wheezing in young children. Wheezy illness has increasingly been recognised as an important cause of morbidity in African children, but there is little information on the contribution of HRV to this. The aim of this study was to determine the role of HRV as a cause of acute wheezing in South African children. METHODS: Two hundred and twenty children presenting consecutively at a tertiary children's hospital with a wheezing illness from May 2004 to November 2005 were prospectively enrolled. A nasal swab was taken and reverse transcription PCR used to screen the samples for HRV. The presence of human metapneumovirus, human bocavirus and human coronavirus-NL63 was assessed in all samples using PCR-based assays. A general shell vial culture using a pool of monoclonal antibodies was used to detect other common respiratory viruses on 26% of samples. Phylogenetic analysis to determine circulating HRV species was performed on a portion of HRV-positive samples. Categorical characteristics were analysed using Fisher's Exact test. RESULTS: HRV was detected in 128 (58.2%) of children, most (72%) of whom were under 2 years of age. Presenting symptoms between the HRV-positive and negative groups were similar. Most illness was managed with ambulatory therapy, but 45 (35%) were hospitalized for treatment and 3 (2%) were admitted to intensive care. There were no in-hospital deaths. All 3 species of HRV were detected with HRV-C being the most common (52%) followed by HRV-A (37%) and HRV-B (11%). Infection with other respiratory viruses occurred in 20/128 (16%) of HRV-positive children and in 26/92 (28%) of HRV-negative samples. CONCLUSION: HRV may be the commonest viral infection in young South African children with acute wheezing. Infection is associated with mild or moderate clinical disease.",2011 Mar 15,"['Smuts, Heidi E', 'Workman, Lesley J', 'Zar, Heather J']",BMC Infect Dis,,,True
6fad5703e838cae052bc9cd18b32ea812b942fb4,PMC,A Transient Homotypic Interaction Model for the Influenza A Virus NS1 Protein Effector Domain,http://dx.doi.org/10.1371/journal.pone.0017946,PMC3065461,21464929,CC BY,"Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal ‘tail’. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed ‘helix-closed’ and ‘helix-open’) in virus-infected cells. ‘Helix-closed’ conformations appear to enhance dsRNA binding, and ‘helix-open’ conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins.",2011 Mar 28,"['Kerry, Philip S.', 'Ayllon, Juan', 'Taylor, Margaret A.', 'Hass, Claudia', 'Lewis, Andrew', 'García-Sastre, Adolfo', 'Randall, Richard E.', 'Hale, Benjamin G.', 'Russell, Rupert J.']",PLoS One,,,True
335f41145ff784047aa5a0ae829be50613c65038,PMC,Is Generalized Maternal Optimism or Pessimism During Pregnancy Associated with Unplanned Cesarean Section Deliveries in China?,http://dx.doi.org/10.1155/2010/754938,PMC3065811,21490743,CC BY,"This research examines whether maternal optimism/pessimism is associated with unplanned Cesarean section deliveries in China. If so, does the association remain after controlling for clinical factors associated with C-sections? A sample of 227 mostly primiparous women in the third trimester of pregnancy was surveyed in a large tertiary care hospital in Beijing, China. Post-delivery data were collected from medical records. In bivariate analysis, both optimism and pessimism were related to unplanned c-section. However, when optimism and pessimism were entered into a regression model together, optimism was no longer statistically significant. Pessimism remained significant, even when adjusting for clinical factors such as previous abortion, previous miscarriage, pregnancy complications, infant gestational age, infant birthweight, labor duration, birth complications, and self-rated difficulty of the pregnancy. This research suggests that maternal mindset during pregnancy has a role in mode of delivery. However, more research is needed to elucidate potential causal pathways and test potential interventions.",2010 Jan 5,"['Moyer, Cheryl A.', 'Elsayed, Yasmin', 'Zhu, YuChun', 'Wei, Yumei', 'Engmann, Cyril M.', 'Yang, Huixia']",J Pregnancy,,,True
b6b73f121cfd9d486f77bae744fa2a7e09df51f4,PMC,In Vitro Gene Delivery Mediated by Asialofetuin-Appended Cationic Liposomes Associated with γ-Cyclodextrin into Hepatocytes,http://dx.doi.org/10.1155/2011/476137,PMC3065884,21490752,CC BY,"The purpose of this study is to evaluate in vitro gene delivery mediated by asialofetuin-appended cationic liposomes (AF-liposomes) associating cyclodextrins (CyD/AF-liposomes) as a hepatocyte-selective nonviral vector. Of various CyDs, AF-liposomes associated with plasmid DNA (pDNA) and γ-cyclodextrin (γ-CyD) (pDNA/γ-CyD/AF-liposomes) showed the highest gene transfer activity in HepG2 cells without any significant cytotoxicity. In addition, γ-CyD enhanced the encapsulation ratio of pDNA with AF-liposomes, and also increased gene transfer activity as the entrapment ratio of pDNA into AF-liposomes was increased. γ-CyD stabilized the liposomal membrane of AF-liposomes and inhibited the release of calcein from AF-liposomes. The stabilizing effect of γ-CyD may be, at least in part, involved in the enhancing gene transfer activity of pDNA/γ-CyD/AF-liposomes. Therefore, these results suggest the potential use of γ-CyD for an enhancer of transfection efficiency of AF-liposomes.",2011 Dec 9,"['Motoyama, Keiichi', 'Nakashima, Yoshihiro', 'Aramaki, Yukihiko', 'Hirayama, Fumitoshi', 'Uekama, Kaneto', 'Arima, Hidetoshi']",J Drug Deliv,,,True
1968f8d8ffe3f695372d919c9966b1ca412b83d2,PMC,Induction of Cyclooxygenase-2 Expression by Hepatitis B Virus Depends on Demethylation-associated Recruitment of Transcription Factors to the Promoter,http://dx.doi.org/10.1186/1743-422X-8-118,PMC3066118,21401943,CC BY,"BACKGROUND: The hepatitis B virus (HBV) is a major etiological factor of inflammation and damage to the liver resulting in hepatocellular carcinoma. Transcription factors play important roles in the disordered gene expression and liver injury caused by HBV. However, the molecular mechanisms behind this observation have not been defined. RESULTS: In this study, we observed that circulating prostaglandin (PGE) 2 synthesis was increased in patients with chronic hepatitis B infection, and detected elevated cyclooxygenase (COX)-2 expression in HBV- and HBx-expressing liver cells. Likewise, the association of HBx with C/EBPβ contributed to the induction of COX-2. The COX-2 promoter was hypomethylated in HBV-positive cells, and specific demethylation of CpG dinucleotides within each of the two NF-AT sites in the COX-2 promoter resulted in the increased binding affinity of NF-AT to the cognate sites in the promoter, followed by increased COX-2 expression and PGE2 accumulation. The DNA methylatransferase DNMT3B played a key role in the methylation of the COX-2 promoter, and its decreased binding to the promoter was responsible for the regional demethylation of CpG sites, and for the increased binding of transcription factors in HBV-positive cells. CONCLUSION: Our results indicate that upregulation of COX-2 by HBV and HBx is mediated by both demethylation events and recruitment of multiple transcription factors binding to the promoter.",2011 Mar 14,"['Yue, Xin', 'Yang, Fang', 'Yang, Yongbo', 'Mu, Yongxin', 'Sun, Wei', 'Li, Wei', 'Xu, Dongping', 'Wu, Jianguo', 'Zhu, Ying']",Virol J,,,True
ff6b55c00278cf8081dec1ad430940165b23d91e,PMC,Human Rhinovirus Infections in Rural Thailand: Epidemiological Evidence for Rhinovirus as Both Pathogen and Bystander,http://dx.doi.org/10.1371/journal.pone.0017780,PMC3066183,21479259,CC0,"BACKGROUND: We describe human rhinovirus (HRV) detections in SaKaeo province, Thailand. METHODS: From September 1, 2003–August 31, 2005, we tested hospitalized patients with acute lower respiratory illness and outpatient controls without fever or respiratory symptoms for HRVs with polymerase chain reaction and molecularly-typed select HRVs. We compared HRV detection among hospitalized patients and controls and estimated enrollment adjusted incidence. RESULTS: HRVs were detected in 315 (16%) of 1919 hospitalized patients and 27 (9.6%) of 280 controls. Children had the highest frequency of HRV detections (hospitalized: <1 year: 29%, 1–4 year: 29%, ≥65 years: 9%; controls: <1 year: 24%, 1–4 year: 14%, ≥65 years: 2.8%). Enrollment adjusted hospitalized HRV detection rates were highest among persons aged <1 year (1038/100,000 persons/year), 1–4 years (457), and ≥65 years (71). All three HRV species were identified, HRV-A was the most common species in most age groups including children aged <1 year (61%) and all adult age groups. HRV-C was the most common species in the 1–4 year (51%) and 5–19 year age groups (54%). Compared to controls, hospitalized adults (≥19 years) and children were more likely to have HRV detections (odds ratio [OR]: 4.8, 95% confidence interval [CI]: 1.5, 15.8; OR: 2.0, CI: 1.2, 3.3, respectively) and hospitalized children were more likely to have HRV-A (OR 1.7, CI: 0.8, 3.5) or HVR-C (OR 2.7, CI: 1.2, 5.9) detection. CONCLUSIONS: HRV rates were high among hospitalized children and the elderly but asymptomatic children also had substantial HRV detection. HRV (all species), and HRV-A and HRV-C detections were epidemiologically-associated with hospitalized illness. Treatment or prevention modalities effective against HRV could reduce hospitalizations due to HRV in Thailand.",2011 Mar 29,"['Fry, Alicia M.', 'Lu, Xiaoyan', 'Olsen, Sonja J.', 'Chittaganpitch, Malinee', 'Sawatwong, Pongpun', 'Chantra, Somrak', 'Baggett, Henry C.', 'Erdman, Dean']",PLoS One,,,True
f82bb9d2d37888e87a1f8f42c7f898a809c3bc94,PMC,A Mutation in Myo15 Leads to Usher-Like Symptoms in LEW/Ztm-ci2 Rats,http://dx.doi.org/10.1371/journal.pone.0015669,PMC3066203,21479269,CC BY,"The LEW/Ztm-ci2 rat is an animal model for syndromal deafness that arose from a spontaneous mutation. Homozygous animals show locomotor abnormalities like lateralized circling behavior. Additionally, an impaired vision can be observed in some animals through behavioral studies. Syndromal deafness as well as retinal degeneration are features of the Usher syndrome in humans. In the present study, the mutation was identified as a base substitution (T->C) in exon 56 of Myo15, leading to an amino acid exchange from leucine (Leu) to proline (Pro) within the carboxy-terminal MyTH4 domain in the proteins' tail region. Myo15 mRNA was expressed in the retina as demonstrated for the first time with the help of in-situ hybridization and PCR. To characterize the visual phenotype, rats were examined by scotopic and photopic electroretinography and, additionally, histological analyses of the retinas were conducted. The complete loss of sight was detected along with a severe degeneration of photoreceptor cells. Interestingly, the manifestation of the disease does not solely depend on the mutation, but also on environmental factors. Since the LEW/Ztm-ci2 rat features the entire range of symptoms of the human Usher syndrome we think that this strain is an appropriate model for this disease. Our findings display that mutations in binding domains of myosin XV do not only cause non-syndromic hearing loss but can also lead to syndromic disorders including retinal dysfunction.",2011 Mar 29,"['Held, Nadine', 'Smits, Bart M. G.', 'Gockeln, Roland', 'Schubert, Stephanie', 'Nave, Heike', 'Northrup, Emily', 'Cuppen, Edwin', 'Hedrich, Hans J.', 'Wedekind, Dirk']",PLoS One,,,True
8996c8a004bc82aca37ba1f1f4265868503ce69f,PMC,Participation of the Cell Polarity Protein PALS1 to T-Cell Receptor-Mediated NF-κB Activation,http://dx.doi.org/10.1371/journal.pone.0018159,PMC3068181,21479189,CC BY,"BACKGROUND: Beside their established function in shaping cell architecture, some cell polarity proteins were proposed to participate to lymphocyte migration, homing, scanning, as well as activation following antigen receptor stimulation. Although PALS1 is a central component of the cell polarity network, its expression and function in lymphocytes remains unknown. Here we investigated whether PALS1 is present in T cells and whether it contributes to T Cell-Receptor (TCR)-mediated activation. METHODOLOGY/PRINCIPAL FINDINGS: By combining RT-PCR and immunoblot assays, we found that PALS1 is constitutively expressed in human T lymphocytes as well as in Jurkat T cells. siRNA-based knockdown of PALS1 hampered TCR-induced activation and optimal proliferation of lymphocyte. We further provide evidence that PALS1 depletion selectively hindered TCR-driven activation of the transcription factor NF-κB. CONCLUSIONS: The cell polarity protein PALS1 is expressed in T lymphocytes and participates to the optimal activation of NF-κB following TCR stimulation.",2011 Mar 30,"['Carvalho, Gabrielle', 'Poalas, Konstantinos', 'Demian, Catherine', 'Hatchi, Emeline', 'Vazquez, Aimé', 'Bidère, Nicolas']",PLoS One,,,True
a7c6ab514af0b9e5edc73e08e496ceb65111cfa9,PMC,A Canadian Critical Care Trials Group project in collaboration with the international forum for acute care trialists - Collaborative H1N1 Adjuvant Treatment pilot trial (CHAT): study protocol and design of a randomized controlled trial,http://dx.doi.org/10.1186/1745-6215-12-70,PMC3068961,21388549,CC BY,"BACKGROUND: Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes. METHODS/DESIGN: A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates. DISCUSSION: Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research. Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic. TRIAL REGISTRATION NUMBER: ISRCTN45190901",2011 Mar 9,"['Burns, Karen EA', 'Chant, Clarence', 'Smith, Orla', 'Cuthbertson, Brian', 'Fowler, Robert', 'Cook, Deborah J', 'Kruger, Peter', 'Webb, Steve', 'Alhashemi, Jamal', 'Dominguez-Cherit, Guillermo', 'Zala, Carlos', 'Rubenfeld, Gordon D', 'Marshall, John C']",Trials,,,True
335e894a725e26adfe71b89170e3fc1301eafb1c,PMC,Dissection of the Influenza A Virus Endocytic Routes Reveals Macropinocytosis as an Alternative Entry Pathway,http://dx.doi.org/10.1371/journal.ppat.1001329,PMC3068995,21483486,CC BY,"Influenza A virus (IAV) enters host cells upon binding of its hemagglutinin glycoprotein to sialylated host cell receptors. Whereas dynamin-dependent, clathrin-mediated endocytosis (CME) is generally considered as the IAV infection pathway, some observations suggest the occurrence of an as yet uncharacterized alternative entry route. By manipulating entry parameters we established experimental conditions that allow the separate analysis of dynamin-dependent and -independent entry of IAV. Whereas entry of IAV in phosphate-buffered saline could be completely inhibited by dynasore, a specific inhibitor of dynamin, a dynasore-insensitive entry pathway became functional in the presence of fetal calf serum. This finding was confirmed with the use of small interfering RNAs targeting dynamin-2. In the presence of serum, both IAV entry pathways were operational. Under these conditions entry could be fully blocked by combined treatment with dynasore and the amiloride derivative EIPA, the hallmark inhibitor of macropinocytosis, whereas either drug alone had no effect. The sensitivity of the dynamin-independent entry pathway to inhibitors or dominant-negative mutants affecting actomyosin dynamics as well as to a number of specific inhibitors of growth factor receptor tyrosine kinases and downstream effectors thereof all point to the involvement of macropinocytosis in IAV entry. Consistently, IAV particles and soluble FITC-dextran were shown to co-localize in cells in the same vesicles. Thus, in addition to the classical dynamin-dependent, clathrin-mediated endocytosis pathway, IAV enters host cells by a dynamin-independent route that has all the characteristics of macropinocytosis.",2011 Mar 31,"['de Vries, Erik', 'Tscherne, Donna M.', 'Wienholts, Marleen J.', 'Cobos-Jiménez, Viviana', 'Scholte, Florine', 'García-Sastre, Adolfo', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",PLoS Pathog,,,True
b3751edcd573ad46664235ecd8b63e9db99d4c09,PMC,Alpha-COPI Coatomer Protein Is Required for Rough Endoplasmic Reticulum Whorl Formation in Mosquito Midgut Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0018150,PMC3069061,21483820,CC BY,"BACKGROUND: One of the early events in midgut epithelial cells of Aedes aegypti mosquitoes is the dynamic reorganization of rough endoplasmic reticulum (RER) whorl structures coincident with the onset of blood meal digestion. Based on our previous studies showing that feeding on an amino acid meal induces TOR signaling in Ae. aegypti, we used proteomics and RNAi to functionally identify midgut epithelial cell proteins that contribute to RER whorl formation. METHODOLOGY/PRINCIPAL FINDINGS: Adult female Ae. aegypti mosquitoes were maintained on sugar alone (unfed), or fed an amino acid meal, and then midgut epithelial cells were analyzed by electron microscopy and protein biochemistry. The size and number of RER whorls in midgut epithelial cells were found to decrease significantly after feeding, and several KDEL-containing proteins were shown to have altered expression levels. LC-MS/MS mass spectrometry was used to analyze midgut microsomal proteins isolated from unfed and amino acid fed mosquitoes, and of the 127 proteins identified, 8 were chosen as candidate whorl forming proteins. Three candidate proteins were COPI coatomer subunits (alpha, beta, beta'), all of which appeared to be present at higher levels in microsomal fractions from unfed mosquitoes. Using RNAi to knockdown alpha-COPI expression, electron microscopy revealed that both the size and number of RER whorls were dramatically reduced in unfed mosquitoes, and moreover, that extended regions of swollen RER were prevalent in fed mosquitoes. Lastly, while a deficiency in alpha-COPI had no effect on early trypsin protein synthesis or secretion 3 hr post blood meal (PBM), expression of late phase proteases at 24 hr PBM was completely blocked. CONCLUSIONS: alpha-COPI was found to be required for the formation of RER whorls in midgut epithelial cells of unfed Aa. aegypti mosquitoes, as well as for the expression of late phase midgut proteases.",2011 Mar 31,"['Zhou, Guoli', 'Isoe, Jun', 'Day, W. Antony', 'Miesfeld, Roger L.']",PLoS One,,,True
da263831b51c583027932f156c45463780ea35fe,PMC,"Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study",http://dx.doi.org/10.1186/1471-2377-11-37,PMC3071317,21435231,CC BY,"BACKGROUND: The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood. METHODS: Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/- 11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/- 11.8 yrs.) who fulfilled criteria for fibromyalgia. RESULTS: Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post- SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms. CONCLUSIONS: The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.",2011 Mar 24,"['Moldofsky, Harvey', 'Patcai, John']",BMC Neurol,,,True
828433debf53d822b26035b951ec78a6f3009de1,PMC,"Vomiting and wasting disease associated with hemagglutinating encephalomyelitis viruses infection in piglets in jilin, china",http://dx.doi.org/10.1186/1743-422X-8-130,PMC3071789,21418610,CC BY,"One coronavirus strain was isolated from brain tissues of ten piglets with evident clinical manifestations of vomiting, diarrhea and dyskinesia in Jilin province in China. Antigenic and genomic characterizations of the virus (isolate PHEV-JLsp09) were based on multiplex PCR and negative staining electron microscopy and sequence analysis of the Hemagglutinin-esterase (HE) gene. These piglets were diagnosed with Porcine hemagglutinating encephalomyelitis virus (PHEV). Necropsy was performed on the piglets. Major pathological changes included meningeal hyperemia, meningeal hemorrhage and cortical hemorrhage. Minor changes were also observed in other organs. Histopathological changes included satellitosis and neuronophagia in the cerebral cortex. Mice were infected with the isolated virus. Their histopathological changes were similar to those symptoms observed in the piglets, exhibiting typical changes for non-suppurative encephalitis. Thus, Porcine hemagglutinating encephalomyelitis virus mainly causes damage to the nervous system but also impacts other organs. This viral strain (isolate PHEV-JLsp09) found in the Siping area of Jilin Province in China is evolutionally closest to the HEV-67N stain (North American strain), indicating that this viral strain evolved from the PHEV from North America.",2011 Mar 21,"['Gao, Wei', 'Zhao, Kui', 'Zhao, Chuanbo', 'Du, Chongtao', 'Ren, Wenzhi', 'Song, Deguang', 'Lu, Huijun', 'Chen, Keyan', 'Li, Zhiping', 'Lan, Yungang', 'Xie, Shengnan', 'He, Wenqi', 'Gao, Feng']",Virol J,,,True
64fe1b9afa90e2e1ea0c1c10e2ae5ada566e270a,PMC,"Genetic characterization of avian influenza subtype H4N6 and H4N9 from live bird market, Thailand",http://dx.doi.org/10.1186/1743-422X-8-131,PMC3071790,21418614,CC BY,"A one year active surveillance program for influenza A viruses among avian species in a live-bird market (LBM) in Bangkok, Thailand was conducted in 2009. Out of 970 samples collected, influenza A virus subtypes H4N6 (n = 2) and H4N9 (n = 1) were isolated from healthy Muscovy ducks. All three viruses were characterized by whole genome sequencing with subsequent phylogenetic analysis and genetic comparison. Phylogenetic analysis of all eight viral genes showed that the viruses clustered in the Eurasian lineage of influenza A viruses. Genetic analysis showed that H4N6 and H4N9 viruses display low pathogenic avian influenza characteristics. The HA cleavage site and receptor binding sites were conserved and resembled to LPAI viruses. This study is the first to report isolation of H4N6 and H4N9 viruses from birds in LBM in Thailand and shows the genetic diversity of the viruses circulating in the LBM. In addition, co-infection of H4N6 and H4N9 in the same Muscovy duck was observed.",2011 Mar 21,"['Wisedchanwet, Trong', 'Wongphatcharachai , Manoosak', 'Boonyapisitsopa, Supanat', 'Bunpapong, Napawan', 'Kitikoon, Pravina', 'Amonsin, Alongkorn']",Virol J,,,True
475c8599530b970bbf476ee0e2798f5940dc1254,PMC,Vaccine Potential of Nipah Virus-Like Particles,http://dx.doi.org/10.1371/journal.pone.0018437,PMC3071823,21494680,CC BY,"Nipah virus (NiV) was first recognized in 1998 in a zoonotic disease outbreak associated with highly lethal febrile encephalitis in humans and a predominantly respiratory disease in pigs. Periodic deadly outbreaks, documentation of person-to-person transmission, and the potential of this virus as an agent of agroterror reinforce the need for effective means of therapy and prevention. In this report, we describe the vaccine potential of NiV virus-like particles (NiV VLPs) composed of three NiV proteins G, F and M. Co-expression of these proteins under optimized conditions resulted in quantifiable amounts of VLPs with many virus-like/vaccine desirable properties including some not previously described for VLPs of any paramyxovirus: The particles were fusogenic, inducing syncytia formation; PCR array analysis showed NiV VLP-induced activation of innate immune defense pathways; the surface structure of NiV VLPs imaged by cryoelectron microscopy was dense, ordered, and repetitive, and consistent with similarly derived structure of paramyxovirus measles virus. The VLPs were composed of all the three viral proteins as designed, and their intracellular processing also appeared similar to NiV virions. The size, morphology and surface composition of the VLPs were consistent with the parental virus, and importantly, they retained their antigenic potential. Finally, these particles, formulated without adjuvant, were able to induce neutralizing antibody response in Balb/c mice. These findings indicate vaccine potential of these particles and will be the basis for undertaking future protective efficacy studies in animal models of NiV disease.",2011 Apr 6,"['Walpita, Pramila', 'Barr, Jennifer', 'Sherman, Michael', 'Basler, Christopher F.', 'Wang, Linfa']",PLoS One,,,True
417006f8744a4d8068ce146b06db09bbd48eaad2,PMC,Insights from Modeling the 3D Structure of New Delhi Metallo-β-Lactamse and Its Binding Interactions with Antibiotic Drugs,http://dx.doi.org/10.1371/journal.pone.0018414,PMC3073942,21494599,CC BY,"New Delhi metallo-beta-lactamase (NDM-1) is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotic drugs. This is because it can inactivate most beta-lactam antibiotic drugs by hydrolyzing them. For in-depth understanding of the hydrolysis mechanism, the three-dimensional structure of NDM-1 was developed. With such a structural frame, two enzyme-ligand complexes were derived by respectively docking Imipenem and Meropenem (two typical beta-lactam antibiotic drugs) to the NDM-1 receptor. It was revealed from the NDM-1/Imipenem complex that the antibiotic drug was hydrolyzed while sitting in a binding pocket of NDM-1 formed by nine residues. And for the case of NDM-1/Meropenem complex, the antibiotic drug was hydrolyzed in a binding pocket formed by twelve residues. All these constituent residues of the two binding pockets were explicitly defined and graphically labeled. It is anticipated that the findings reported here may provide useful insights for developing new antibiotic drugs to overcome the resistance problem.",2011 Apr 11,"['Wang, Jing-Fang', 'Chou, Kuo-Chen']",PLoS One,,,True
27548472c288a185911a8907c927d18f3c9b0abe,PMC,Production of IFN-β during Listeria monocytogenes Infection Is Restricted to Monocyte/Macrophage Lineage,http://dx.doi.org/10.1371/journal.pone.0018543,PMC3073975,21494554,CC BY,"The family of type I interferons (IFN), which consists of several IFN-α and one IFN-β, are produced not only after stimulation by viruses, but also after infection with non-viral pathogens. In the course of bacterial infections, these cytokines could be beneficial or detrimental. IFN-β is the primary member of type I IFN that initiates a cascade of IFN-α production. Here we addressed the question which cells are responsible for IFN-β expression after infection with the intracellular pathogen Listeria monocytogenes by using a genetic approach. By means of newly established reporter mice, maximum of IFN-β expression was observed at 24 hours post infection in spleen and, surprisingly, 48 hours post infection in colonized cervical and inguinal lymph nodes. Colonization of lymph nodes was independent of the type I IFN signaling, as well as bacterial dose and strain. Using cell specific reporter function and conditional deletions we could define cells expressing LysM as the major IFN-β producers, with cells formerly defined as Tip-DCs being the highest. Neutrophilic granulocytes, dendritic cells and plasmacytoid dendritic cells did not significantly contribute to type I IFN production.",2011 Apr 11,"['Solodova, Evgenia', 'Jablonska, Jadwiga', 'Weiss, Siegfried', 'Lienenklaus, Stefan']",PLoS One,,,True
21a539cc5e6c5ce8c39d80a59033791d7860a8b0,PMC,Modification of PCV-2 virulence by substitution of the genogroup motif of the capsid protein,http://dx.doi.org/10.1186/1297-9716-42-54,PMC3074528,21435235,CC BY,"Porcine circovirus type 2 (PCV-2) is the causal agent of the post-weaning multisystemic wasting syndrome (PMWS). PCV-2 are small single-stranded circular DNA viruses clustered into two main genogroups: PCV-2a and PCV-2b. Each genogroup present a specific highly-conserved motif of six amino acids (between amino acids 86 and 91) in the PCV-2 capsid protein. The aim of this study was to verify whether the motif located in the capsid protein and specific to each PCV-2 genogroup contributes to virulence. Two parental DNA clones, PCV-2a and PCV-2b, were constructed as well as two mutants DNA clones, PCV-2a/motif 2b and PCV-2b/motif 2a by exchanging the capsid motif of each genogroup. The four DNA clones were characterized in vitro as well as in vivo. Cells transfected by the four DNA clones produced infectious viruses. In specific-pathogen-free piglets transfected by the four infectious DNA clones, PCV-2b/motif 2a virulence was not attenuated while the PCV-2a/motif 2b virulence was drastically reduced compared to their parent virulence. These results suggest that the amino acids between positions 86 and 91 of the capsid protein are determinant for the virulence of isolates. However, the environment of this motif seems also involved.",2011 Mar 24,"['Allemandou, Aude', 'Grasland, Béatrice', 'Hernandez-Nignol, Anne-Cécile', ""Kéranflec'h, André"", 'Cariolet, Roland', 'Jestin, André']",Vet Res,,,True
ddf12f9e4ca7761aa1c1fd192e9bc9103ad8a642,PMC,Antigen-Specific Monoclonal Antibodies Isolated from B Cells Expressing Constitutively Active STAT5,http://dx.doi.org/10.1371/journal.pone.0017189,PMC3078118,21525985,CC BY,"BACKGROUND: Fully human monoclonal antibodies directed against specific pathogens have a high therapeutic potential, but are difficult to generate. METHODOLOGY/PRINCIPAL FINDINGS: Memory B cells were immortalized by expressing an inducible active mutant of the transcription factor Signal Transducer and Activator of Transcription 5 (STAT5). Active STAT5 inhibits the differentiation of B cells while increasing their replicative life span. We obtained cloned B cell lines, which produced antibodies in the presence of interleukin 21 after turning off STAT5. We used this method to obtain monoclonal antibodies against the model antigen tetanus toxin. CONCLUSIONS/SIGNIFICANCE: Here we describe a novel and relatively simple method of immortalizing antigen-specific human B cells for isolation of human monoclonal antibodies. These results show that STAT5 overexpression can be employed to isolate antigen specific antibodies from human memory B cells.",2011 Apr 15,"['Scheeren, Ferenc A.', 'van Geelen, Caroline M. M.', 'Yasuda, Etsuko', 'Spits, Hergen', 'Beaumont, Tim']",PLoS One,,,True
21caf0c49864b6af4c62e68e3ff7374e14c16537,PMC,Genomic Characterization and High Prevalence of Bocaviruses in Swine,http://dx.doi.org/10.1371/journal.pone.0017292,PMC3078135,21525999,CC BY,"Using random PCR amplification followed by plasmid subcloning and DNA sequencing, we detected bocavirus related sequences in 9 out of 17 porcine stool samples. Using primer walking, we sequenced the nearly complete genomes of two highly divergent bocaviruses we provisionally named porcine bocavirus 1 isolate H18 (PBoV1-H18) and porcine bocavirus 2 isolate A6 (PBoV2-A6) which differed by 51.8% in their NS1 protein. Phylogenetic analysis indicated that PBoV1-H18 was very closely related to a ∼2 Kb central region of a porcine bocavirus-like virus (PBo-LikeV) from Sweden described in 2009. PBoV2-A6 was very closely related to the porcine bocavirus genomes PBoV-1 and PBoV2 from China described in 2010. Among 340 fecal samples collected from different age, asymptomatic swine in five Chinese provinces, the prevalence of PBoV1-H18 and PBoV2-A6 related viruses were 45–75% and 55–70% respectively, with 30–47% of pigs co-infected. PBoV1-A6 related strains were highly conserved, while PBoV2-H18 related strains were more diverse, grouping into two genotypes corresponding to the previously described PBoV1 and PBoV2. Together with the recently described partial bocavirus genomes labeled V6 and V7, a total of three major porcine bocavirus clades have therefore been described to date. Further studies will be required to elucidate the possible pathogenic impact of these diverse bocaviruses either alone or in combination with other porcine viruses.",2011 Apr 15,"['Shan, Tongling', 'Lan, Daoliang', 'Li, Linlin', 'Wang, Chunmei', 'Cui, Li', 'Zhang, Wen', 'Hua, Xiuguo', 'Zhu, Caixia', 'Zhao, Wei', 'Delwart, Eric']",PLoS One,,,True
a642d4021e92bf6974af05b20f17e6e8b25c368c,PMC,Viral and Atypical Bacterial Detection in Acute Respiratory Infection in Children Under Five Years,http://dx.doi.org/10.1371/journal.pone.0018928,PMC3078930,21533115,CC BY,"BACKGROUND: Acute respiratory infection (ARI) is a leading cause of morbidity and mortality in children worldwide. This study aimed to determine the viral and atypical bacterial causes of different severities and clinical manifestations of ARI in preschool children from low-income families in North-East Brazil. METHODS: Clinical/demographic data and nasopharyngeal aspirates (NPA) were prospectively collected from children <5 years presenting with ARI over one year to a paediatric A&E department. Disease severity was grouped according to presence of lower respiratory tract signs, need for hospital admission and need for oxygen. Clinical manifestation of ARI was based on discharge diagnosis from hospital with four conditions predominating: bronchiolitis, pneumonia, episodic viral wheeze/asthma and upper respiratory tract infection. Multiplex PCR was used to detect 17 common respiratory viral and atypical bacterial pathogens in NPA. FINDINGS: 407 children with a median age of eight months were recruited. Pathogens were detected in 85·5% samples with co-infection being particularly common (39·5%). Respiratory Syncytial Virus (RSV; 37%), Adenoviruses (AdV; 25%), Rhinoviruses (hRV; 19%), Bocavirus (hBoV; 19%), human Meta-pneumovirus (hMPV; 10%) and Mycoplasma pneumoniae (Mpp; 10%) were most prevalent. Detection and co-infection rates were similar in all severities and clinical manifestations of ARI apart from RSV, which was associated with more severe disease and specifically more severe cases of bronchiolitis, and Mpp, which was associated with more severe cases of pneumonia. Mpp was detected in 17% of children admitted to hospital with pneumonia. INTERPRETATION: This study underlines the importance of viral and atypical bacterial pathogens in ARI in pre-school children and highlights the complex epidemiology of these pathogens in this age group. Generally, viruses and atypical bacteria were detected in all severities and clinical manifestations of ARI but RSV and Mpp were associated with more severe cases of bronchiolitis and pneumonia respectively.",2011 Apr 18,"['Bezerra, Patrícia G. M.', 'Britto, Murilo C. A.', 'Correia, Jailson B.', 'Duarte, Maria do Carmo M. B.', 'Fonceca, Angela M.', 'Rose, Katie', 'Hopkins, Mark J.', 'Cuevas, Luis E.', 'McNamara, Paul S.']",PLoS One,,,True
408e677725167e4c45863aab7d91de0a5dae6d22,PMC,Communicating uncertainty - how Australian television reported H1N1 risk in 2009: a content analysis,http://dx.doi.org/10.1186/1471-2458-11-181,PMC3079644,21435263,CC BY,"BACKGROUND: Health officials face particular challenges in communicating with the public about emerging infectious diseases of unknown severity such as the 2009 H1N1(swine 'flu) pandemic (pH1N1). Statements intended to create awareness and convey the seriousness of infectious disease threats can draw accusations of scare-mongering, while officials can be accused of complacency if such statements are not made. In these communication contexts, news journalists, often reliant on official sources to understand issues are pivotal in selecting and emphasising aspects of official discourse deemed sufficiently newsworthy to present to the public. This paper presents a case-study of news communication regarding the emergence of pH1N1. METHODS: We conducted a content analysis of all television news items about pH1N1. We examined news and current affairs items broadcast on 5 free-to-air Sydney television channels between April 25 2009 (the first report) and October 9 (prior to the vaccine release) for statements about [1] the seriousness of the disease [2] how the public could minimise contagion [3] government responses to emerging information. RESULTS: pH1N1 was the leading health story for eight of 24 weeks and was in the top 5 for 20 weeks. 353 news items were identified, yielding 3086 statements for analysis, with 63.4% related to the seriousness of the situation, 12.9% providing advice for viewers and 23.6% involving assurances from government. Coverage focused on infection/mortality rates, the spread of the virus, the need for public calm, the vulnerability of particular groups, direct and indirect advice for viewers, and government reassurances about effective management. CONCLUSIONS: Overall, the reporting of 2009 pH1N1 in Sydney, Australia was generally non-alarmist, while conveying that pH1N1 was potentially serious. Daily infection rate tallies and commentary on changes in the pandemic alert level were seldom contextualised to assist viewers in understanding personal relevance. Suggestions are made about how future reporting of emerging infectious diseases could be enhanced.",2011 Mar 24,"['Fogarty, Andrea S', 'Holland, Kate', 'Imison, Michelle', 'Blood, R Warwick', 'Chapman, Simon', 'Holding, Simon']",BMC Public Health,,,True
568cf52b425ceaf8d1e9a14bbd088c493e8fd4fe,PMC,Analysis of codon usage and nucleotide composition bias in polioviruses,http://dx.doi.org/10.1186/1743-422X-8-146,PMC3079669,21450075,CC BY,"BACKGROUND: Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and a member of the family of Picornaviridae and among the most rapidly evolving viruses known. Analysis of codon usage can reveal much about the molecular evolution of the viruses. However, little information about synonymous codon usage pattern of polioviruses genome has been acquired to date. METHODS: The relative synonymous codon usage (RSCU) values, effective number of codon (ENC) values, nucleotide contents and dinucleotides were investigated and a comparative analysis of codon usage pattern for open reading frames (ORFs) among 48 polioviruses isolates including 31 of genotype 1, 13 of genotype 2 and 4 of genotype 3. RESULTS: The result shows that the overall extent of codon usage bias in poliovirus samples is low (mean ENC = 53.754 > 40). The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in those polioviruses. Depending on the RSCU data, it was found that there was a significant variation in bias of codon usage among three genotypes. Geographic factor also has some effect on the codon usage pattern (exists in the genotype-1 of polioviruses). No significant effect in gene length or vaccine derived polioviruses (DVPVs), wild viruses and live attenuated virus was observed on the variations of synonymous codon usage in the virus genes. The relative abundance of dinucleotide (CpG) in the ORFs of polioviruses are far below expected values especially in DVPVs and attenuated virus of polioviruses genotype 1. CONCLUSION: The information from this study may not only have theoretical value in understanding poliovirus evolution, especially for DVPVs genotype 1, but also have potential value for the development of poliovirus vaccines.",2011 Mar 30,"['Zhang, Jie', 'Wang, Meng', 'Liu, Wen-qian', 'Zhou, Jian-hua', 'Chen, Hao-tai', 'Ma, Li-na', 'Ding, Yao-zhong', 'Gu, Yuan-xing', 'Liu, Yong-sheng']",Virol J,,,True
5d2c1aaad487ae9b76099721947c8948a57ebba3,PMC,Comparative Pathogenesis of Three Human and Zoonotic SARS-CoV Strains in Cynomolgus Macaques,http://dx.doi.org/10.1371/journal.pone.0018558,PMC3080360,21533129,CC BY,"The severe acute respiratory syndrome (SARS) epidemic was characterized by increased pathogenicity in the elderly due to an early exacerbated innate host response. SARS-CoV is a zoonotic pathogen that entered the human population through an intermediate host like the palm civet. To prevent future introductions of zoonotic SARS-CoV strains and subsequent transmission into the human population, heterologous disease models are needed to test the efficacy of vaccines and therapeutics against both late human and zoonotic isolates. Here we show that both human and zoonotic SARS-CoV strains can infect cynomolgus macaques and resulted in radiological as well as histopathological changes similar to those seen in mild human cases. Viral replication was higher in animals infected with a late human phase isolate compared to a zoonotic isolate. While there were significant differences in the number of host genes differentially regulated during the host responses between the three SARS-CoV strains, the top pathways and functions were similar and only apparent early during infection with the majority of genes associated with interferon signaling pathways. This study characterizes critical disease models in the evaluation and licensure of therapeutic strategies against SARS-CoV for human use.",2011 Apr 20,"['Rockx, Barry', 'Feldmann, Friederike', 'Brining, Douglas', 'Gardner, Don', 'LaCasse, Rachel', 'Kercher, Lisa', 'Long, Dan', 'Rosenke, Rebecca', 'Virtaneva, Kimmo', 'Sturdevant, Daniel E.', 'Porcella, Stephen F.', 'Mattoon, John', 'Parnell, Michael', 'Baric, Ralph S.', 'Feldmann, Heinz']",PLoS One,,,True
f5f53c6d9a31095c447315d0c2ebc42cbcebcfd2,PMC,Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism,http://dx.doi.org/10.1186/1479-0556-9-8,PMC3080791,21477292,CC BY,"BACKGROUND: The envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV) can efficiently pseudotype lentiviral vectors. Some strains of LCMV exploit high affinity interactions with α-dystroglycan (α-DG) to bind to cell surfaces and subsequently fuse in low pH endosomes. LCMV strains with low α-DG affinity utilize an unknown receptor and display unique tissue tropisms. We pseudotyped non-primate feline immunodeficiency virus (FIV) vectors using LCMV derived glycoproteins with high or low affinity to α-DG and evaluated their properties in vitro and in vivo. METHODS: We pseudotyped FIV with the LCMV WE54 strain envelope glycoprotein and also engineered a point mutation in the WE54 envelope glycoprotein (L260F) to diminish α-DG affinity and direct binding to alternate receptors. We hypothesized that this change would alter in vivo tissue tropism and enhance gene transfer to neonatal animals. RESULTS: In mice, hepatic α- and β-DG expression was greatest at the late gestational and neonatal time points. When displayed on the surface of the FIV lentivirus the WE54 L260F mutant glycoprotein bound weakly to immobilized α-DG. Additionally, LCMV WE54 pseudotyped FIV vector transduction was neutralized by pre-incubation with soluble α-DG, while the mutant glycoprotein pseudotyped vector was not. In vivo gene transfer in adult mice with either envelope yielded low transduction efficiencies in hepatocytes following intravenous delivery. In marked contrast, neonatal gene transfer with the LCMV envelopes, and notably with the FIV-L260F vector, conferred abundant liver and lower level cardiomyocyte transduction as detected by luciferase assays, bioluminescent imaging, and β-galactosidase staining. CONCLUSIONS: These results suggest that a developmentally regulated receptor for LCMV is expressed abundantly in neonatal mice. LCMV pseudotyped vectors may have applications for neonatal gene transfer. ABBREVIATIONS: Armstrong 53b (Arm53b); baculovirus Autographa californica GP64 (GP64); charge-coupled device (CCD); dystroglycan (DG); feline immunodeficiency virus (FIV); glycoprotein precursor (GP-C); firefly luciferase (Luc); lymphocytic choriomeningitis virus (LCMV); nuclear targeted β-galactosidase (ntLacZ); optical density (OD); PBS/0.1% (w/v) Tween-20 (PBST); relative light units (RLU); Rous sarcoma virus (RSV); transducing units per milliliter (TU/ml); vesicular stomatitis virus (VSV-G); wheat germ agglutinin (WGA); 50% reduction in binding (C(50)).",2011 Apr 8,"['Dylla, Douglas E', 'Xie, Litao', 'Michele, Daniel E', 'Kunz, Stefan', 'McCray, Paul B']",Genet Vaccines Ther,,,True
b3574701bdaf6c4d408e9abe2d4176e058fc5208,PMC,"Size-Segregated Particle Number Concentrations and Respiratory Emergency Room Visits in Beijing, China",http://dx.doi.org/10.1289/ehp.1002203,PMC3080933,21118783,CC0,"BACKGROUND: The link between concentrations of particulate matter (PM) and respiratory morbidity has been investigated in numerous studies. OBJECTIVES: The aim of this study was to analyze the role of different particle size fractions with respect to respiratory health in Beijing, China. METHODS: Data on particle size distributions from 3 nm to 1 μm; PM(10) (PM ≤ 10 μm), nitrogen dioxide (NO(2)), and sulfur dioxide concentrations; and meteorologic variables were collected daily from March 2004 to December 2006. Concurrently, daily counts of emergency room visits (ERV) for respiratory diseases were obtained from the Peking University Third Hospital. We estimated pollutant effects in single- and two-pollutant generalized additive models, controlling for meteorologic and other time-varying covariates. Time-delayed associations were estimated using polynomial distributed lag, cumulative effects, and single lag models. RESULTS: Associations of respiratory ERV with NO(2) concentrations and 100–1,000 nm particle number or surface area concentrations were of similar magnitude—that is, approximately 5% increase in respiratory ERV with an interquartile range increase in air pollution concentration. In general, particles < 50 nm were not positively associated with ERV, whereas particles 50–100 nm were adversely associated with respiratory ERV, both being fractions of ultrafine particles. Effect estimates from two-pollutant models were most consistent for NO(2). CONCLUSIONS: Present levels of air pollution in Beijing were adversely associated with respiratory ERV. NO(2) concentrations seemed to be a better surrogate for evaluating overall respiratory health effects of ambient air pollution than PM(10) or particle number concentrations in Beijing.",2011 Apr 30,"['Leitte, Arne Marian', 'Schlink, Uwe', 'Herbarth, Olf', 'Wiedensohler, Alfred', 'Pan, Xiao-Chuan', 'Hu, Min', 'Richter, Matthia', 'Wehner, Birgit', 'Tuch, Thomas', 'Wu, Zhijun', 'Yang, Minjuan', 'Liu, Liqun', 'Breitner, Susanne', 'Cyrys, Josef', 'Peters, Annette', 'Wichmann, H.-Erich', 'Franck, Ulrich']",Environ Health Perspect,,,True
91312e3e01c328ebc4c8007586a84e8cfbdf45e9,PMC,"Novel, Divergent Simian Hemorrhagic Fever Viruses in a Wild Ugandan Red Colobus Monkey Discovered Using Direct Pyrosequencing",http://dx.doi.org/10.1371/journal.pone.0019056,PMC3081318,21544192,CC BY,"BACKGROUND: Simian hemorrhagic fever virus (SHFV) has caused lethal outbreaks of hemorrhagic disease in captive primates, but its distribution in wild primates has remained obscure. Here, we describe the discovery and genetic characterization by direct pyrosequencing of two novel, divergent SHFV variants co-infecting a single male red colobus monkey from Kibale National Park, Uganda. METHODOLOGY/PRINCIPAL FINDINGS: The viruses were detected directly from blood plasma using pyrosequencing, without prior virus isolation and with minimal PCR amplification. The two new SHFV variants, SHFV-krc1 and SHFV-krc2 are highly divergent from each other (51.9% nucleotide sequence identity) and from the SHFV type strain LVR 42-0/M6941 (52.0% and 51.8% nucleotide sequence identity, respectively) and demonstrate greater phylogenetic diversity within SHFV than has been documented within any other arterivirus. Both new variants nevertheless have the same 3′ genomic architecture as the type strain, containing three open reading frames not present in the other arteriviruses. CONCLUSIONS/SIGNIFICANCE: These results represent the first documentation of SHFV in a wild primate and confirm the unusual 3′ genetic architecture of SHFV relative to the other arteriviruses. They also demonstrate a degree of evolutionary divergence within SHFV that is roughly equivalent to the degree of divergence between other arterivirus species. The presence of two such highly divergent SHFV variants co-infecting a single individual represents a degree of within-host viral diversity that exceeds what has previously been reported for any arterivirus. These results expand our knowledge of the natural history and diversity of the arteriviruses and underscore the importance of wild primates as reservoirs for novel pathogens.",2011 Apr 22,"['Lauck, Michael', 'Hyeroba, David', 'Tumukunde, Alex', 'Weny, Geoffrey', 'Lank, Simon M.', 'Chapman, Colin A.', ""O'Connor, David H."", 'Friedrich, Thomas C.', 'Goldberg, Tony L.']",PLoS One,,,True
1b92fda04723ae9d30a58f10b054cc1b7971e870,PMC,CD4-Independent Human Immunodeficiency Virus Infection Involves Participation of Endocytosis and Cathepsin B,http://dx.doi.org/10.1371/journal.pone.0019352,PMC3081840,21541353,CC BY,"During a comparison of the infectivity of mNDK, a CD4-independent human immunodeficiency virus type 1 (HIV-1) strain, to various cell lines, we found that HeLa cells were much less susceptible than 293T and TE671 cells. Hybridoma cells between HeLa and 293T cells were as susceptible as 293T cells, suggesting that cellular factors enhance the mNDK infection in 293T cells. By screening a cDNA expression library in HeLa cells, cystatin C was isolated as an enhancer of the mNDK infection. Because cathepsin B protease, a natural ligand of cystatin C, was upregulated in HeLa cells, we speculated that the high levels of cathepsin B activities were inhibitory to the CD4-independent infection and that cystatin C enhanced the infection by impairing the excessive cathepsin B activity. Consistent with this idea, pretreatment of HeLa cells with 125 µM of CA-074Me, a cathepsin B inhibitor, resulted in an 8-fold enhancement of the mNDK infectivity. Because cathepsin B is activated by low pH in acidic endosomes, we further examined the potential roles of endosomes in the CD4-independent infection. Suppression of endosome acidification or endocytosis by inhibitors or by an Eps15 dominant negative mutant reduced the infectivity of mNDK in which CD4-dependent infections were not significantly impaired. Taken together, these results suggest that endocytosis, endosomal acidification, and cathepsin B activity are involved in the CD4-independent entry of HIV-1.",2011 Apr 25,"['Yoshii, Hiroaki', 'Kamiyama, Haruka', 'Goto, Kensuke', 'Oishi, Kazunori', 'Katunuma, Nobuhiko', 'Tanaka, Yuetsu', 'Hayashi, Hideki', 'Matsuyama, Toshifumi', 'Sato, Hironori', 'Yamamoto, Naoki', 'Kubo, Yoshinao']",PLoS One,,,True
0baa7fbb346a50319eb57a4a1556c3f48938d0e6,PMC,Live Bird Markets of Bangladesh: H9N2 Viruses and the Near Absence of Highly Pathogenic H5N1 Influenza,http://dx.doi.org/10.1371/journal.pone.0019311,PMC3082571,21541296,CC BY,"Avian influenza surveillance in Bangladesh has been passive, relying on poultry farmers to report suspected outbreaks of highly pathogenic H5N1 influenza. Here, the results of an active surveillance effort focusing on the live-bird markets are presented. Prevalence of influenza infection in the birds of the live bird markets is 23.0%, which is similar to that in poultry markets in other countries. Nearly all of the isolates (94%) were of the non-pathogenic H9N2 subtype, but viruses of the H1N2, H1N3, H3N6, H4N2, H5N1, and H10N7 subtypes were also observed. The highly pathogenic H5N1-subtype virus was observed at extremely low prevalence in the surveillance samples (0.08%), and we suggest that the current risk of infection for humans in the retail poultry markets in Bangladesh is negligible. However, the high prevalence of the H9 subtype and its potential for interaction with the highly pathogenic H5N1-subtype, i.e., reassortment and attenuation of host morbidity, highlight the importance of active surveillance of the poultry markets.",2011 Apr 26,"['Negovetich, Nicholas J.', 'Feeroz, Mohammed M.', 'Jones-Engel, Lisa', 'Walker, David', 'Alam, S. M. Rabiul', 'Hasan, Kamrul', 'Seiler, Patrick', 'Ferguson, Angie', 'Friedman, Kim', 'Barman, Subrata', 'Franks, John', 'Turner, Jasmine', 'Krauss, Scott', 'Webby, Richard J.', 'Webster, Robert G.']",PLoS One,,,True
47b84b720b0601da21090660ed223b7cfa1150cb,PMC,Monitoring Influenza Activity in the United States: A Comparison of Traditional Surveillance Systems with Google Flu Trends,http://dx.doi.org/10.1371/journal.pone.0018687,PMC3083406,21556151,CC0,"BACKGROUND: Google Flu Trends was developed to estimate US influenza-like illness (ILI) rates from internet searches; however ILI does not necessarily correlate with actual influenza virus infections. METHODS AND FINDINGS: Influenza activity data from 2003–04 through 2007–08 were obtained from three US surveillance systems: Google Flu Trends, CDC Outpatient ILI Surveillance Network (CDC ILI Surveillance), and US Influenza Virologic Surveillance System (CDC Virus Surveillance). Pearson's correlation coefficients with 95% confidence intervals (95% CI) were calculated to compare surveillance data. An analysis was performed to investigate outlier observations and determine the extent to which they affected the correlations between surveillance data. Pearson's correlation coefficient describing Google Flu Trends and CDC Virus Surveillance over the study period was 0.72 (95% CI: 0.64, 0.79). The correlation between CDC ILI Surveillance and CDC Virus Surveillance over the same period was 0.85 (95% CI: 0.81, 0.89). Most of the outlier observations in both comparisons were from the 2003–04 influenza season. Exclusion of the outlier observations did not substantially improve the correlation between Google Flu Trends and CDC Virus Surveillance (0.82; 95% CI: 0.76, 0.87) or CDC ILI Surveillance and CDC Virus Surveillance (0.86; 95%CI: 0.82, 0.90). CONCLUSIONS: This analysis demonstrates that while Google Flu Trends is highly correlated with rates of ILI, it has a lower correlation with surveillance for laboratory-confirmed influenza. Most of the outlier observations occurred during the 2003–04 influenza season that was characterized by early and intense influenza activity, which potentially altered health care seeking behavior, physician testing practices, and internet search behavior.",2011 Apr 27,"['Ortiz, Justin R.', 'Zhou, Hong', 'Shay, David K.', 'Neuzil, Kathleen M.', 'Fowlkes, Ashley L.', 'Goss, Christopher H.']",PLoS One,,,True
49f01042ee1df642748c8b65f2abde687b2750ed,PMC,Antioxidant Status and Immune Activity of Glycyrrhizin in Allergic Rhinitis Mice,http://dx.doi.org/10.3390/ijms12020905,PMC3083680,21541033,CC BY,"Oxidative stress is considered as a major risk factor that contributes to increased lipid peroxidation and declined antioxidants in some degenerative diseases. Glycyrrhizin is widely used to cure allergic diseases due to its medicinal properties. In the present study, we evaluated the role of glycyrrhizin on lipid peroxidation and antioxidant status in the blood and nasal mucosa of allergic rhinitis (AR) mice. Mice were divided into six groups: normal control mice, model control (MC) mice, three glycyrrhizin-treated mice groups and lycopene-treated mice. Sensitization-associated increase in lipid peroxidation was observed in the blood and nasal mucosa of MC mice. Activities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), total antioxidant capacity (TAOC) and levels of glutathione (GSH) were found to be significantly decreased in the blood and nasal mucosa in MC mice when compared to normal control mice. However, normalized lipid peroxidation and antioxidant defenses were reported in the glycyrrhizin-treated and lycopene-treated mice. Moreover, glycyrrhizin treatment still enhanced IFN-γ and reduced IL-4 levels in glycyrrhizin-treated mice. These findings demonstrated that glycyrrhizin treatment enhanced the antioxidant status and decreased the incidence of free radical-induced lipid peroxidation and improved immunity activities in the blood and nasal mucosa of AR mice.",2011 Jan 26,"['Li, Xiao-Lan', 'Zhou, Ai-Guo', 'Zhang, Li', 'Chen, Wei-Jun']",Int J Mol Sci,,,True
b3fe63ea9f4794d58f37083f3430c6e5238449c3,PMC,Evaluation of a Novel Non-Penetrating Electrode for Use in DNA Vaccination,http://dx.doi.org/10.1371/journal.pone.0019181,PMC3084774,21559474,CC BY,"Current progress in the development of vaccines has decreased the incidence of fatal and non-fatal infections and increased longevity. However, new technologies need to be developed to combat an emerging generation of infectious diseases. DNA vaccination has been demonstrated to have great potential for use with a wide variety of diseases. Alone, this technology does not generate a significant immune response for vaccination, but combined with delivery by electroporation (EP), can enhance plasmid expression and immunity. Most EP systems, while effective, can be invasive and painful making them less desirable for use in vaccination. Our lab recently developed a non-invasive electrode known as the multi-electrode array (MEA), which lies flat on the surface of the skin without penetrating the tissue. In this study we evaluated the MEA for its use in DNA vaccination using Hepatitis B virus as the infectious model. We utilized the guinea pig model because their skin is similar in thickness and morphology to humans. The plasmid encoding Hepatitis B surface antigen (HBsAg) was delivered intradermally with the MEA to guinea pig skin. The results show increased protein expression resulting from plasmid delivery using the MEA as compared to injection alone. Within 48 hours of treatment, there was an influx of cellular infiltrate in experimental groups. Humoral responses were also increased significantly in both duration and intensity as compared to injection only groups. While this electrode requires further study, our results suggest that the MEA has potential for use in electrically mediated intradermal DNA vaccination.",2011 Apr 29,"['Donate, Amy', 'Coppola, Domenico', 'Cruz, Yolmari', 'Heller, Richard']",PLoS One,,,True
0c04a2b5c4c91d76c26736dd05ce6fc6385cc167,PMC,LILRA3 Binds Both Classical and Non-Classical HLA Class I Molecules but with Reduced Affinities Compared to LILRB1/LILRB2: Structural Evidence,http://dx.doi.org/10.1371/journal.pone.0019245,PMC3084784,21559424,CC BY,"Structurally, Group 1 LILR (Leukocyte Immunogloblin (Ig)-Like Receptor, also known as Ig-like transcripts, ILT; Leukocyte Ig-like receptor, LIR; and CD85) members are very similar in terms of the HLAIs (human leukocyte antigen class I molecules) binding region and were hypothesized that they all bind to HLAIs. As one of the Group 1 LILRs, LILRA3 is the only secretory LILR and may greatly control the inhibitory immune response induced by LILRB1, LILRB2, and other HLA-binding LILR molecules like LILRA1. Nevertheless, little was known about the binding of LILRA3 to HLAIs. In this report, we present the crystal structure of the LILRA3 domain 1 (D1) and evaluate the D1 and D1D2 (domain 1 and domain 2) binding to classical and non-classical HLAIs using BIAcore® surface plasmon resonance analysis (SPR). We found that LILRA3 binds both classical HLA-A*0201 and non-classical HLA-G1 but with reduced affinities compared to either LILRB1 or LILRB2. The polymorphic amino acids and the LILRA3 D1 structure support this notion.",2011 Apr 29,"['Ryu, Myongchol', 'Chen, Yong', 'Qi, Jianxun', 'Liu, Jun', 'Fan, Zheng', 'Nam, Gol', 'Shi, Yi', 'Cheng, Hao', 'Gao, George F.']",PLoS One,,,True
2c468e84bbaa10edb38eb112ab8088e74073c02f,PMC,Monitoring the Systemic Human Memory B Cell Compartment of Melanoma Patients for Anti-Tumor IgG Antibodies,http://dx.doi.org/10.1371/journal.pone.0019330,PMC3084832,21559411,CC BY,"Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (P<0.0001). Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21) (P<0.0001). Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800) compared to 2% of cultures from healthy controls (n = 600) produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer.",2011 Apr 29,"['Gilbert, Amy E.', 'Karagiannis, Panagiotis', 'Dodev, Tihomir', 'Koers, Alexander', 'Lacy, Katie', 'Josephs, Debra H.', 'Takhar, Pooja', 'Geh, Jenny L. C.', 'Healy, Ciaran', 'Harries, Mark', 'Acland, Katharine M.', 'Rudman, Sarah M.', 'Beavil, Rebecca L.', 'Blower, Philip J.', 'Beavil, Andrew J.', 'Gould, Hannah J.', 'Spicer, James', 'Nestle, Frank O.', 'Karagiannis, Sophia N.']",PLoS One,,,True
cfffac30aa716974333312a44475097d94c8f475,PMC,Visualizing Clinical Evidence: Citation Networks for the Incubation Periods of Respiratory Viral Infections,http://dx.doi.org/10.1371/journal.pone.0019496,PMC3084881,21559339,CC BY,"Simply by repetition, medical facts can become enshrined as truth even when there is little empirical evidence supporting them. We present an intuitive and clear visual design for tracking the citation history of a particular scientific fact over time. We apply this method to data from a previously published literature review on the incubation period of nine respiratory viral infections. The resulting citation networks reveal that the conventional wisdom about the incubation period for these diseases was based on a small fraction of available data and in one case, on no retrievable empirical evidence. Overall, 50% of all incubation period statements did not provide a source for their estimate and 65% of original sources for incubation period data were not incorporated into subsequent publications. More standardized and widely available methods for visualizing these histories of medical evidence are needed to ensure that conventional wisdom cannot stray too far from empirically supported knowledge.",2011 Apr 29,"['Reich, Nicholas G.', 'Perl, Trish M.', 'Cummings, Derek A. T.', 'Lessler, Justin']",PLoS One,,,True
7d84b116132df661fef2f697880e3856e1e4ca8a,PMC,Visualizing Clinical Evidence: Citation Networks for the Incubation Periods of Respiratory Viral Infections,http://dx.doi.org/10.1371/journal.pone.0019496,PMC3084881,21559339,CC BY,"Simply by repetition, medical facts can become enshrined as truth even when there is little empirical evidence supporting them. We present an intuitive and clear visual design for tracking the citation history of a particular scientific fact over time. We apply this method to data from a previously published literature review on the incubation period of nine respiratory viral infections. The resulting citation networks reveal that the conventional wisdom about the incubation period for these diseases was based on a small fraction of available data and in one case, on no retrievable empirical evidence. Overall, 50% of all incubation period statements did not provide a source for their estimate and 65% of original sources for incubation period data were not incorporated into subsequent publications. More standardized and widely available methods for visualizing these histories of medical evidence are needed to ensure that conventional wisdom cannot stray too far from empirically supported knowledge.",2011 Apr 29,"['Reich, Nicholas G.', 'Perl, Trish M.', 'Cummings, Derek A. T.', 'Lessler, Justin']",PLoS One,,,True
21e6d4c42e4375fcb05eeebb140a805461688542,PMC,Visualizing Clinical Evidence: Citation Networks for the Incubation Periods of Respiratory Viral Infections,http://dx.doi.org/10.1371/journal.pone.0019496,PMC3084881,21559339,CC BY,"Simply by repetition, medical facts can become enshrined as truth even when there is little empirical evidence supporting them. We present an intuitive and clear visual design for tracking the citation history of a particular scientific fact over time. We apply this method to data from a previously published literature review on the incubation period of nine respiratory viral infections. The resulting citation networks reveal that the conventional wisdom about the incubation period for these diseases was based on a small fraction of available data and in one case, on no retrievable empirical evidence. Overall, 50% of all incubation period statements did not provide a source for their estimate and 65% of original sources for incubation period data were not incorporated into subsequent publications. More standardized and widely available methods for visualizing these histories of medical evidence are needed to ensure that conventional wisdom cannot stray too far from empirically supported knowledge.",2011 Apr 29,"['Reich, Nicholas G.', 'Perl, Trish M.', 'Cummings, Derek A. T.', 'Lessler, Justin']",PLoS One,,,True
d04d63e56673f57ed326ebf2314e5b8192266a79,PMC,Transmission Potential of Chikungunya Virus and Control Measures: The Case of Italy,http://dx.doi.org/10.1371/journal.pone.0018860,PMC3086881,21559329,CC BY,"During summer 2007 Italy has experienced an epidemic caused by Chikungunya virus – the first large outbreak documented in a temperate climate country – with approximately 161 laboratory confirmed cases concentrated in two bordering villages in North–Eastern Italy comprising 3,968 inhabitants. The seroprevalence was recently estimated to be 10.2%. In this work we provide estimates of the transmission potential of the virus and we assess the efficacy of the measures undertaken by public health authorities to control the epidemic spread. To such aim, we developed a model describing the temporal dynamics of the competent vector, known as Aedes albopictus, explicitly depending on climatic factors, coupled to an epidemic transmission model describing the spread of the epidemic in both humans and mosquitoes. The cumulative number of notified cases predicted by the model was 185 on average (95% CI 117–278), in good agreement with observed data. The probability of observing a major outbreak after the introduction of an infective human case was estimated to be in the range of 32%–76%. We found that the basic reproduction number was in the range of 1.8–6 but it could have been even larger, depending on the density of mosquitoes, which in turn depends on seasonal meteorological effects, besides other local abiotic factors. These results confirm the increasing risk of tropical vector–borne diseases in temperate climate countries, as a consequence of globalization. However, our results show that an epidemic can be controlled by performing a timely intervention, even if the transmission potential of Chikungunya virus is sensibly high.",2011 May 3,"['Poletti, Piero', 'Messeri, Gianni', 'Ajelli, Marco', 'Vallorani, Roberto', 'Rizzo, Caterina', 'Merler, Stefano']",PLoS One,,,True
438e817dea190348df99e09a8e519fc64101b899,PMC,Analysis of synonymous codon usage in Hepatitis A virus,http://dx.doi.org/10.1186/1743-422X-8-174,PMC3087699,21496278,CC BY,"BACKGROUND: Hepatitis A virus is the causative agent of type A viral hepatitis, which causes occasional acute hepatitis. Nevertheless, little information about synonymous codon usage pattern of HAV genome in the process of its evolution is available. In this study, the key genetic determinants of codon usage in HAV were examined. RESULTS: The overall extent of codon usage bias in HAV is high in Picornaviridae. And the patterns of synonymous codon usage are quite different in HAV genomes from different location. The base composition is closely correlated with codon usage bias. Furthermore, the most important determinant that results in such a high codon bias in HAV is mutation pressure rather than natural selection. CONCLUSIONS: HAV presents a higher codon usage bias than other members of Picornaviridae. Compositional constraint is a significant element that influences the variation of synonymous codon usage in HAV genome. Besides, mutation pressure is supposed to be the major factor shaping the hyperendemic codon usage pattern of HAV.",2011 Apr 16,"['Zhang, Yiqiang', 'Liu, Yongsheng', 'Liu, Wenqian', 'Zhou, Jianhua', 'Chen, Haotai', 'Wang, Yin', 'Ma, Lina', 'Ding, Yaozhong', 'Zhang, Jie']",Virol J,,,True
96ba8069882d695675b9e2e6d32c3640910735b4,PMC,Clustering Heart Rate Dynamics Is Associated with β-Adrenergic Receptor Polymorphisms: Analysis by Information-Based Similarity Index,http://dx.doi.org/10.1371/journal.pone.0019232,PMC3087751,21573230,CC BY,"BACKGROUND: Genetic polymorphisms in the gene encoding the β-adrenergic receptors (β-AR) have a pivotal role in the functions of the autonomic nervous system. Using heart rate variability (HRV) as an indicator of autonomic function, we present a bottom-up genotype–phenotype analysis to investigate the association between β-AR gene polymorphisms and heart rate dynamics. METHODS: A total of 221 healthy Han Chinese adults (59 males and 162 females, aged 33.6±10.8 years, range 19 to 63 years) were recruited and genotyped for three common β-AR polymorphisms: β(1)-AR Ser49Gly, β(2)-AR Arg16Gly and β(2)-AR Gln27Glu. Each subject underwent two hours of electrocardiogram monitoring at rest. We applied an information-based similarity (IBS) index to measure the pairwise dissimilarity of heart rate dynamics among study subjects. RESULTS: With the aid of agglomerative hierarchical cluster analysis, we categorized subjects into major clusters, which were found to have significantly different distributions of β(2)-AR Arg16Gly genotype. Furthermore, the non-randomness index, a nonlinear HRV measure derived from the IBS method, was significantly lower in Arg16 homozygotes than in Gly16 carriers. The non-randomness index was negatively correlated with parasympathetic-related HRV variables and positively correlated with those HRV indices reflecting a sympathovagal shift toward sympathetic activity. CONCLUSIONS: We demonstrate a bottom-up categorization approach combining the IBS method and hierarchical cluster analysis to detect subgroups of subjects with HRV phenotypes associated with β-AR polymorphisms. Our results provide evidence that β(2)-AR polymorphisms are significantly associated with the acceleration/deceleration pattern of heart rate oscillation, reflecting the underlying mode of autonomic nervous system control.",2011 May 4,"['Yang, Albert C.', 'Tsai, Shih-Jen', 'Hong, Chen-Jee', 'Wang, Cynthia', 'Chen, Tai-Jui', 'Liou, Ying-Jay', 'Peng, Chung-Kang']",PLoS One,,,True
822233763421a1e054abbc49c00a8726cb3ebfe1,PMC,Distribution of the Phenotypic Effects of Random Homologous Recombination between Two Virus Species,http://dx.doi.org/10.1371/journal.ppat.1002028,PMC3088723,21573141,CC BY,"Recombination has an evident impact on virus evolution and emergence of new pathotypes, and has generated an immense literature. However, the distribution of phenotypic effects caused by genome-wide random homologous recombination has never been formally investigated. Previous data on the subject have promoted the implicit view that most viral recombinant genomes are likely to be deleterious or lethal if the nucleotide identity of parental sequences is below 90%. We decided to challenge this view by creating a bank of near-random recombinants between two viral species of the genus Begomovirus (Family Geminiviridae) exhibiting 82% nucleotide identity, and by testing infectivity and in planta accumulation of recombinant clones randomly extracted from this bank. The bank was created by DNA-shuffling—a technology initially applied to the random shuffling of individual genes, and here implemented for the first time to shuffle full-length viral genomes. Together with our previously described system allowing the direct cloning of full-length infectious geminivirus genomes, it provided a unique opportunity to generate hundreds of “mosaic” virus genomes, directly testable for infectivity. A subset of 47 randomly chosen recombinants was sequenced, individually inoculated into tomato plants, and compared with the parental viruses. Surprisingly, our results showed that all recombinants were infectious and accumulated at levels comparable or intermediate to that of the parental clones. This indicates that, in our experimental system, despite the fact that the parental genomes differ by nearly 20%, lethal and/or large deleterious effects of recombination are very rare, in striking contrast to the common view that has emerged from previous studies published on other viruses.",2011 May 5,"['Vuillaume, Florence', 'Thébaud, Gaël', 'Urbino, Cica', 'Forfert, Nadège', 'Granier, Martine', 'Froissart, Rémy', 'Blanc, Stéphane', 'Peterschmitt, Michel']",PLoS Pathog,,,True
82448eac471a17fd751603f9b91450b6961d3a0e,PMC,Action Mechanisms of Lithium Chloride on Cell Infection by Transmissible Gastroenteritis Coronavirus,http://dx.doi.org/10.1371/journal.pone.0018669,PMC3089605,21573100,CC BY,"Transmissible gastroenteritis virus (TGEV) is a porcine coronavirus. Lithium chloride (LiCl) has been found to be effective against several DNA viruses, such as Herpes simplex virus and vaccinia virus. Recently, we and others have reported the inhibitory effect of LiCl on avian infectious bronchitis coronavirus (IBV) infection, an RNA virus. In the current study, the action mechanism of LiCl on cell infection by TGEV was investigated. Plaque assays and 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenyl tetrazoliumbromide (MTT) assays showed that the cell infection by TGEV was inhibited in a dose-dependent manner, when LiCl was added to virus-infected cells; the cell infection was not affected when either cells or viruses were pretreated with the drug. The inhibition of TGEV infection in vitro by LiCl was observed at different virus doses and with different cell lines. The inhibitory effect of LiCl against TGEV infection and transcription was confirmed by RT-PCR and real-time PCR targeting viral S and 3CL-protease genes. The time-of-addition effect of the drug on TGEV infection indicated that LiCl acted on the initial and late stage of TGEV infection. The production of virus was not detected at 36 h post-infection due to the drug treatment. Moreover, immunofluorescence (IF) and flow cytometry analyses based on staining of Annexin V and propidium iodide staining of nuclei indicated that early and late cell apoptosis induced by TGEV was inhibited efficiently. The ability of LiCl to inhibit apoptosis was investigated by IF analysis of caspase-3 expression. Our data indicate that LiCl inhibits TGEV infection by exerting an anti-apoptotic effect. The inhibitory effect of LiCl was also observed with porcine epidemic diarrhea coronavirus. Together with other reports concerning the inhibitory effect of lithium salts on IBV in cell culture, our results indicate that LiCl may be a potent agent against porcine and avian coronaviruses.",2011 May 6,"['Ren, Xiaofeng', 'Meng, Fandan', 'Yin, Jiechao', 'Li, Guangxing', 'Li, Xunliang', 'Wang, Chao', 'Herrler, Georg']",PLoS One,,,True
aae339db3ebacca2632136e51dac48f209a952f6,PMC,The Infection of Chicken Tracheal Epithelial Cells with a H6N1 Avian Influenza Virus,http://dx.doi.org/10.1371/journal.pone.0018894,PMC3089607,21573102,CC BY,"Sialic acids (SAs) linked to galactose (Gal) in α2,3- and α2,6-configurations are the receptors for avian and human influenza viruses, respectively. We demonstrate that chicken tracheal ciliated cells express α2,3-linked SA, while goblet cells mainly express α2,6-linked SA. In addition, the plant lectin MAL-II, but not MAA/MAL-I, is bound to the surface of goblet cells, suggesting that SA2,3-linked oligosaccharides with Galβ1–3GalNAc subterminal residues are specifically present on the goblet cells. Moreover, both α2,3- and α2,6-linked SAs are detected on single tracheal basal cells. At a low multiplicity of infection (MOI) avian influenza virus H6N1 is exclusively detected in the ciliated cells, suggesting that the ciliated cell is the major target cell of the H6N1 virus. At a MOI of 1, ciliated, goblet and basal cells are all permissive to the AIV infection. This result clearly elucidates the receptor distribution for the avian influenza virus among chicken tracheal epithelial cells and illustrates a primary cell model for evaluating the cell tropisms of respiratory viruses in poultry.",2011 May 6,"['Shen, Ching-I', 'Wang, Ching-Ho', 'Shen, Shih-Cheng', 'Lee, Hsiu-Chin', 'Liao, Jiunn-Wang', 'Su, Hong-Lin']",PLoS One,,,True
01c25f9838ef8e005bf720c4f76e67a9f1038ff0,PMC,Classification of viral zoonosis through receptor pattern analysis,http://dx.doi.org/10.1186/1471-2105-12-96,PMC3090355,21489240,CC BY,"BACKGROUND: Viral zoonosis, the transmission of a virus from its primary vertebrate reservoir species to humans, requires ubiquitous cellular proteins known as receptor proteins. Zoonosis can occur not only through direct transmission from vertebrates to humans, but also through intermediate reservoirs or other environmental factors. Viruses can be categorized according to genotype (ssDNA, dsDNA, ssRNA and dsRNA viruses). Among them, the RNA viruses exhibit particularly high mutation rates and are especially problematic for this reason. Most zoonotic viruses are RNA viruses that change their envelope proteins to facilitate binding to various receptors of host species. In this study, we sought to predict zoonotic propensity through the analysis of receptor characteristics. We hypothesized that the major barrier to interspecies virus transmission is that receptor sequences vary among species--in other words, that the specific amino acid sequence of the receptor determines the ability of the viral envelope protein to attach to the cell. RESULTS: We analysed host-cell receptor sequences for their hydrophobicity/hydrophilicity characteristics. We then analysed these properties for similarities among receptors of different species and used a statistical discriminant analysis to predict the likelihood of transmission among species. CONCLUSIONS: This study is an attempt to predict zoonosis through simple computational analysis of receptor sequence differences. Our method may be useful in predicting the zoonotic potential of newly discovered viral strains.",2011 Apr 13,"['Bae, Se-Eun', 'Son, Hyeon Seok']",BMC Bioinformatics,,,True
bd0d94a4452f2b55cfab53adecb84ce5f2c91fe3,PMC,Lysosomotropic agents as HCV entry inhibitors,http://dx.doi.org/10.1186/1743-422X-8-163,PMC3090357,21481279,CC BY,"HCV has two envelop proteins named as E1 and E2 which play an important role in cell entry through two main pathways: direct fusion at the plasma membrane and receptor-mediated endocytosis. Fusion of the HCV envelope proteins is triggered by low pH within the endosome. Lysosomotropic agents (LA) such as Chloroquine and Ammonium chloride (NH(4)Cl) are the weak bases and penetrate in lysosome as protonated form and increase the intracellular pH. To investigate the antiviral effect of LA (Chloroquine and NH(4)Cl) on pH dependent endocytosis, HCV pseudoparticles (HCVpp) of 1a and 3a genotype were produced and used to infect liver cells. The toxicological effects of Chloroquine and NH(4)Cl were tested in liver cells through MTT cell proliferation assay. For antiviral screening of Chloroquine and NH(4)Cl, liver cells were infected with HCVpp of 3a and 1a genotype in the presence or absence of different concentrations of Chloroquine and NH4Cl and there luciferase activity was determined by using a luminometer. The results demonstrated that Chloroquine and NH(4)Cl showed more than 50% reduction of virus infectivity at 50 μM and 10 mM concentrations respectively. These results suggest that inhibition of HCV at fusion step by increasing the lysosomal pH will be better option to treat chronic HCV.",2011 Apr 12,"['Ashfaq, Usman A', 'Javed, Tariq', 'Rehman, Sidra', 'Nawaz, Zafar', 'Riazuddin, Sheikh']",Virol J,,,True
f5fb2153b992cdc2d4bdb3678e667126c9a27689,PMC,One health: the importance of companion animal vector-borne diseases,http://dx.doi.org/10.1186/1756-3305-4-49,PMC3090364,21489237,CC BY,"The international prominence accorded the 'One Health' concept of co-ordinated activity of those involved in human and animal health is a modern incarnation of a long tradition of comparative medicine, with roots in the ancient civilizations and a golden era during the 19(th )century explosion of knowledge in the field of infectious disease research. Modern One Health tends to focus on zoonotic pathogens emerging from wildlife and production animal species, but one of the most significant One Health challenges is rabies for which there is a canine reservoir. This review considers the role of small companion animals in One Health and specifically addresses the major vector-borne infectious diseases that are shared by man, dogs and cats. The most significant of these are leishmaniosis, borreliosis, bartonellosis, ehrlichiosis, rickettsiosis and anaplasmosis. The challenges that lie ahead in this field of One Health are discussed, together with the role of the newly formed World Small Animal Veterinary Association One Health Committee.",2011 Apr 13,"Day, Michael J",Parasit Vectors,,,True
133933d03341e293921239f0d6a2b3ea4f1f574c,PMC,"A Simple, Inexpensive Device for Nucleic Acid Amplification without Electricity—Toward Instrument-Free Molecular Diagnostics in Low-Resource Settings",http://dx.doi.org/10.1371/journal.pone.0019738,PMC3090398,21573065,CC BY,"BACKGROUND: Molecular assays targeted to nucleic acid (NA) markers are becoming increasingly important to medical diagnostics. However, these are typically confined to wealthy, developed countries; or, to the national reference laboratories of developing-world countries. There are many infectious diseases that are endemic in low-resource settings (LRS) where the lack of simple, instrument-free, NA diagnostic tests is a critical barrier to timely treatment. One of the primary barriers to the practicality and availability of NA assays in LRS has been the complexity and power requirements of polymerase chain reaction (PCR) instrumentation (another is sample preparation). METHODOLOGY/PRINCIPAL FINDINGS: In this article, we investigate the hypothesis that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays. We assess the heater's equivalence to commercially available PCR instruments through the characterization of the temperature profiles produced, and a minimal method comparison. Versions of the prototype for several different isothermal techniques are presented. CONCLUSIONS/SIGNIFICANCE: We demonstrate that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays, and that the results of those assays are not significantly different from ones incubated in parallel in commercially available PCR instruments. These results clearly suggest the potential of the non-instrumented nucleic acid amplification (NINA) heater for molecular diagnostics in LRS. When combined with other innovations in development that eliminate power requirements for sample preparation, cold reagent storage, and readout, the NINA heater will comprise part of a kit that should enable electricity-free NA testing for many important analytes.",2011 May 9,"['LaBarre, Paul', 'Hawkins, Kenneth R.', 'Gerlach, Jay', 'Wilmoth, Jared', 'Beddoe, Andrew', 'Singleton, Jered', 'Boyle, David', 'Weigl, Bernhard']",PLoS One,,,True
c9e36f5f3564f04bfbbcefe1d1eec41078b2eadd,PMC,"A Simple, Inexpensive Device for Nucleic Acid Amplification without Electricity—Toward Instrument-Free Molecular Diagnostics in Low-Resource Settings",http://dx.doi.org/10.1371/journal.pone.0019738,PMC3090398,21573065,CC BY,"BACKGROUND: Molecular assays targeted to nucleic acid (NA) markers are becoming increasingly important to medical diagnostics. However, these are typically confined to wealthy, developed countries; or, to the national reference laboratories of developing-world countries. There are many infectious diseases that are endemic in low-resource settings (LRS) where the lack of simple, instrument-free, NA diagnostic tests is a critical barrier to timely treatment. One of the primary barriers to the practicality and availability of NA assays in LRS has been the complexity and power requirements of polymerase chain reaction (PCR) instrumentation (another is sample preparation). METHODOLOGY/PRINCIPAL FINDINGS: In this article, we investigate the hypothesis that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays. We assess the heater's equivalence to commercially available PCR instruments through the characterization of the temperature profiles produced, and a minimal method comparison. Versions of the prototype for several different isothermal techniques are presented. CONCLUSIONS/SIGNIFICANCE: We demonstrate that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays, and that the results of those assays are not significantly different from ones incubated in parallel in commercially available PCR instruments. These results clearly suggest the potential of the non-instrumented nucleic acid amplification (NINA) heater for molecular diagnostics in LRS. When combined with other innovations in development that eliminate power requirements for sample preparation, cold reagent storage, and readout, the NINA heater will comprise part of a kit that should enable electricity-free NA testing for many important analytes.",2011 May 9,"['LaBarre, Paul', 'Hawkins, Kenneth R.', 'Gerlach, Jay', 'Wilmoth, Jared', 'Beddoe, Andrew', 'Singleton, Jered', 'Boyle, David', 'Weigl, Bernhard']",PLoS One,,,False
f426954f62f73eccb16b672e9e93dfb6d48af618,PMC,The Potential Influence of Common Viral Infections Diagnosed during Hospitalization among Critically Ill Patients in the United States,http://dx.doi.org/10.1371/journal.pone.0018890,PMC3091021,21573031,CC BY,"Viruses are the most common source of infection among immunocompetent individuals, yet they are not considered a clinically meaningful risk factor among the critically ill. This work examines the association of viral infections diagnosed during the hospital stay or not documented as present on admission to the outcomes of ICU patients with no evidence of immunosuppression on admission. This is a population-based retrospective cohort study of University HealthSystem Consortium (UHC) academic centers in the U.S. from the years 2006 to 2009. The UHC is an alliance of over 90% of the non-profit academic medical centers in the U.S. A total of 209,695 critically ill patients were used in this analysis. Eight hospital complications were examined. Patients were grouped into four cohorts: absence of infection, bacterial infection only, viral infection only, and bacterial and viral infection during same hospital admission. Viral infections diagnosed during hospitalization significantly increased the risk of all complications. There was also a seasonal pattern for viral infections. Specific viruses associated with poor outcomes included influenza, RSV, CMV, and HSV. Patients who had both viral and bacterial infections during the same hospitalization had the greatest risk of mortality RR 6.58, 95% CI (5.47, 7.91); multi-organ failure RR 8.25, 95% CI (7.50, 9.07); and septic shock RR 271.2, 95% CI (188.0, 391.3). Viral infections may play a significant yet unrecognized role in the outcomes of ICU patients. They may serve as biological markers or play an active role in the development of certain adverse complications by interacting with coincident bacterial infection.",2011 Apr 29,"['Miggins, Makesha', 'Hasan, Anjum', 'Hohmann, Samuel', 'Southwick, Frederick', 'Casella, George', 'Schain, Denise', 'Liu, Huazhi', 'Bihorac, Azra', 'Moldawer, Lyle', 'Efron, Philip', 'Ang, Darwin']",PLoS One,,,True
04b9001d61d666e065f28a9e628991f4d76d71bc,PMC,"Perceived risk, anxiety, and behavioural responses of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands: results of three consecutive online surveys",http://dx.doi.org/10.1186/1471-2458-11-2,PMC3091536,21199571,CC BY,"BACKGROUND: Research into risk perception and behavioural responses in case of emerging infectious diseases is still relatively new. The aim of this study was to examine perceptions and behaviours of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands. METHODS: Two cross-sectional and one follow-up online survey (survey 1, 30 April-4 May; survey 2, 15-19 June; survey 3, 11-20 August 2009). Adults aged 18 years and above participating in a representative Internet panel were invited (survey 1, n = 456; survey 2, n = 478; follow-up survey 3, n = 934). Main outcome measures were 1) time trends in risk perception, feelings of anxiety, and behavioural responses (survey 1-3) and 2) factors associated with taking preventive measures and strong intention to comply with government-advised preventive measures in the future (survey 3). RESULTS: Between May and August 2009, the level of knowledge regarding Influenza A (H1N1) increased, while perceived severity of the new flu, perceived self-efficacy, and intention to comply with preventive measures decreased. The perceived reliability of information from the government decreased from May to August (62% versus 45%). Feelings of anxiety decreased from May to June, and remained stable afterwards. From June to August 2009, perceived vulnerability increased and more respondents took preventive measures (14% versus 38%). Taking preventive measures was associated with no children in the household, high anxiety, high self-efficacy, more agreement with statements on avoidance, and paying much attention to media information regarding Influenza A (H1N1). Having a strong intention to comply with government-advised preventive measures in the future was associated with higher age, high perceived severity, high anxiety, high perceived efficacy of measures, high self-efficacy, and finding governmental information to be reliable. CONCLUSIONS: Decreasing trends over time in perceived severity and anxiety are consistent with the reality: the clinical picture of influenza turned out to be mild in course of time. Although (inter)national health authorities initially overestimated the case fatality rate, the public stayed calm and remained to have a relatively high intention to comply with preventive measures.",2011 Jan 3,"['Bults, Marloes', 'Beaujean, Desirée JMA', 'de Zwart, Onno', 'Kok, Gerjo', 'van Empelen, Pepijn', 'van Steenbergen, Jim E', 'Richardus, Jan Hendrik', 'Voeten, Hélène ACM']",BMC Public Health,,,True
a8a55f01d9e4a3e3b77512767ab78bb8d1d74a25,PMC,Factors associated with motivation and hesitation to work among health professionals during a public crisis: a cross sectional study of hospital workers in Japan during the pandemic (H1N1) 2009,http://dx.doi.org/10.1186/1471-2458-10-672,PMC3091577,21050482,CC BY,"BACKGROUND: The professionalism of hospital workers in Japan was challenged by the pandemic (H1N1) 2009. To maintain hospital function under critical situations such as a pandemic, it is important to understand the factors that increase and decrease the willingness to work. Previous hospital-based studies have examined this question using hypothetical events, but so far it has not been examined in an actual pandemic. Here, we surveyed the factors that influenced the motivation and hesitation of hospital workers to work in Japan soon after the pandemic (H1N1) 2009. METHODS: Self-administered anonymous questionnaires about demographic character and stress factors were distributed to all 3635 employees at three core hospitals in Kobe city, Japan and were collected from June to July, 2009, about one month after the pandemic (H1N1) in Japan. RESULTS: Of a total of 3635 questionnaires distributed, 1693 (46.7%) valid questionnaires were received. 28.4% (N = 481) of workers had strong motivation and 14.7% (N = 249) had strong hesitation to work. Demographic characters and stress-related questions were categorised into four types according to the odds ratios (OR) of motivation and hesitation to work: some factors increased motivation and lowered hesitation; others increased motivation only; others increased hesitation only and others increased both motivation and hesitation. The strong feeling of being supported by the national and local governments (Multivariate OR: motivation; 3.5; CI 2.2-5.4, hesitation; 0.2; CI 0.1-0.6) and being protected by hospital (Multivariate OR: motivation; 2.8; CI 2.2-3.7, hesitation; 0.5; CI 0.3-0.7) were related to higher motivation and lower hesitation. Here, protection included taking precautions to prevent illness among workers and their families, providing for the care of those who do become ill, reducing malpractice threats, and financial support for families of workers who die on duty. But 94.1% of the respondents answered protection by the national and local government was weak and 79.7% answered protection by the hospital was weak. CONCLUSIONS: Some factors have conflicting effects because they increase both motivation and hesitation. Giving workers the feeling that they are being protected by the national and local government and hospital is especially valuable because it increases their motivation and lowers their hesitation to work.",2010 Nov 4,"['Imai, Hissei', 'Matsuishi, Kunitaka', 'Ito, Atsushi', 'Mouri, Kentaro', 'Kitamura, Noboru', 'Akimoto, Keiko', 'Mino, Koichi', 'Kawazoe, Ayako', 'Isobe, Masanori', 'Takamiya, Shizuo', 'Mita, Tatsuo']",BMC Public Health,,,True
924313134ea2e38b9e48ceaa1177afb92f7a5c03,PMC,Chiropteran types I and II interferon genes inferred from genome sequencing traces by a statistical gene-family assembler,http://dx.doi.org/10.1186/1471-2164-11-444,PMC3091641,20663124,CC BY,"BACKGROUND: The rate of emergence of human pathogens is steadily increasing; most of these novel agents originate in wildlife. Bats, remarkably, are the natural reservoirs of many of the most pathogenic viruses in humans. There are two bat genome projects currently underway, a circumstance that promises to speed the discovery host factors important in the coevolution of bats with their viruses. These genomes, however, are not yet assembled and one of them will provide only low coverage, making the inference of most genes of immunological interest error-prone. Many more wildlife genome projects are underway and intend to provide only shallow coverage. RESULTS: We have developed a statistical method for the assembly of gene families from partial genomes. The method takes full advantage of the quality scores generated by base-calling software, incorporating them into a complete probabilistic error model, to overcome the limitation inherent in the inference of gene family members from partial sequence information. We validated the method by inferring the human IFNA genes from the genome trace archives, and used it to infer 61 type-I interferon genes, and single type-II interferon genes in the bats Pteropus vampyrus and Myotis lucifugus. We confirmed our inferences by direct cloning and sequencing of IFNA, IFNB, IFND, and IFNK in P. vampyrus, and by demonstrating transcription of some of the inferred genes by known interferon-inducing stimuli. CONCLUSION: The statistical trace assembler described here provides a reliable method for extracting information from the many available and forthcoming partial or shallow genome sequencing projects, thereby facilitating the study of a wider variety of organisms with ecological and biomedical significance to humans than would otherwise be possible.",2010 Jul 21,"['Kepler, Thomas B', 'Sample, Christopher', 'Hudak, Kathryn', 'Roach, Jeffrey', 'Haines, Albert', 'Walsh, Allyson', 'Ramsburg, Elizabeth A']",BMC Genomics,,,True
f161447bea90a1e414e3cb22557efe9156bab8e2,PMC,Use of consensus sequences for the design of high density resequencing microarrays: the influenza virus paradigm,http://dx.doi.org/10.1186/1471-2164-11-586,PMC3091733,20961419,CC BY,"BACKGROUND: A resequencing microarray called PathogenID v2.0 has been developed and used to explore various strategies of sequence selection for its design. The part dedicated to influenza viruses was based on consensus sequences specific for one gene generated from global alignments of a large number of influenza virus sequences available in databanks. RESULTS: For each HA (H1, H2, H3, H5, H7 and H9) and NA (N1, N2 and N7) molecular type chosen to be tested, 1 to 3 consensus sequences were computed and tiled on the microarray. A total of 12 influenza virus samples from different host origins (humans, pigs, horses and birds) and isolated over a period of about 50 years were used in this study. Influenza viruses were correctly identified, and in most cases with the accurate information of the time of their emergence. CONCLUSIONS: PathogenID v2.0 microarray demonstrated its ability to type and subtype influenza viruses, often to the level of viral variants, with a minimum number of tiled sequences. This validated the strategy of using consensus sequences, which do not exist in nature, for our microarray design. The versatility, rapidity and high discriminatory power of the PathogenID v2.0 microarray could prove critical to detect and identify viral genome reassortment events resulting in a novel virus with epidemic or pandemic potential and therefore assist health authorities to make efficient decisions about patient treatment and outbreak management.",2010 Oct 20,"['Leclercq, India', 'Berthet, Nicolas', 'Batéjat, Christophe', 'Rousseaux, Claudine', 'Dickinson, Philip', 'Old, Iain G', 'Kong, Katherine', 'Kennedy, Giulia C', 'Cole, Stewart T', 'Manuguerra, Jean-Claude']",BMC Genomics,,,True
9580bfcbdb77b78a21887a8911bb9b69444182a4,PMC,Field Effectiveness of Pandemic and 2009-2010 Seasonal Vaccines against 2009-2010 A(H1N1) Influenza: Estimations from Surveillance Data in France,http://dx.doi.org/10.1371/journal.pone.0019621,PMC3091864,21573005,CC BY,"BACKGROUND: In this study, we assess how effective pandemic and trivalent 2009-2010 seasonal vaccines were in preventing influenza-like illness (ILI) during the 2009 A(H1N1) pandemic in France. We also compare vaccine effectiveness against ILI versus laboratory-confirmed pandemic A(H1N1) influenza, and assess the possible bias caused by using non-specific endpoints and observational data. METHODOLOGY AND PRINCIPAL FINDINGS: We estimated vaccine effectiveness by using the following formula: VE = (PPV-PCV)/(PPV(1-PCV)) × 100%, where PPV is the proportion vaccinated in the population and PCV the proportion of vaccinated influenza cases. People were considered vaccinated three weeks after receiving a dose of vaccine. ILI and pandemic A(H1N1) laboratory-confirmed cases were obtained from two surveillance networks of general practitioners. During the epidemic, 99.7% of influenza isolates were pandemic A(H1N1). Pandemic and seasonal vaccine uptakes in the population were obtained from the National Health Insurance database and by telephonic surveys, respectively. Effectiveness estimates were adjusted by age and week. The presence of residual biases was explored by calculating vaccine effectiveness after the influenza period. The effectiveness of pandemic vaccines in preventing ILI was 52% (95% confidence interval: 30–69) during the pandemic and 33% (4–55) after. It was 86% (56–98) against confirmed influenza. The effectiveness of seasonal vaccines against ILI was 61% (56–66) during the pandemic and 19% (−10–41) after. It was 60% (41–74) against confirmed influenza. CONCLUSIONS: The effectiveness of pandemic vaccines in preventing confirmed pandemic A(H1N1) influenza on the field was high, consistently with published findings. It was significantly lower against ILI. This is unsurprising since not all ILI cases are caused by influenza. Trivalent 2009-2010 seasonal vaccines had a statistically significant effectiveness in preventing ILI and confirmed pandemic influenza, but were not better in preventing confirmed pandemic influenza than in preventing ILI. This lack of difference might be indicative of selection bias.",2011 May 10,"['Pelat, Camille', 'Falchi, Alessandra', 'Carrat, Fabrice', 'Mosnier, Anne', 'Bonmarin, Isabelle', 'Turbelin, Clément', 'Vaux, Sophie', 'van der Werf, Sylvie', 'Cohen, Jean Marie', 'Lina, Bruno', 'Blanchon, Thierry', 'Hanslik, Thomas']",PLoS One,,,True
aad82670f39f4f9731dfeab9064d1063d13c5cb8,PMC,SAGES: A Suite of Freely-Available Software Tools for Electronic Disease Surveillance in Resource-Limited Settings,http://dx.doi.org/10.1371/journal.pone.0019750,PMC3091876,21572957,CC0,"Public health surveillance is undergoing a revolution driven by advances in the field of information technology. Many countries have experienced vast improvements in the collection, ingestion, analysis, visualization, and dissemination of public health data. Resource-limited countries have lagged behind due to challenges in information technology infrastructure, public health resources, and the costs of proprietary software. The Suite for Automated Global Electronic bioSurveillance (SAGES) is a collection of modular, flexible, freely-available software tools for electronic disease surveillance in resource-limited settings. One or more SAGES tools may be used in concert with existing surveillance applications or the SAGES tools may be used en masse for an end-to-end biosurveillance capability. This flexibility allows for the development of an inexpensive, customized, and sustainable disease surveillance system. The ability to rapidly assess anomalous disease activity may lead to more efficient use of limited resources and better compliance with World Health Organization International Health Regulations.",2011 May 10,"['Lewis, Sheri L.', 'Feighner, Brian H.', 'Loschen, Wayne A.', 'Wojcik, Richard A.', 'Skora, Joseph F.', 'Coberly, Jacqueline S.', 'Blazes, David L.']",PLoS One,,,True
a3ad970870495c1bc1fd7cc4eb6f815b486479c8,PMC,"The Global Emerging Infection Surveillance and Response System (GEIS), a U.S. government tool for improved global biosurveillance: a review of 2009",http://dx.doi.org/10.1186/1471-2458-11-S2-S2,PMC3092412,21388562,CC BY,"The Armed Forces Health Surveillance Center, Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) has the mission of performing surveillance for emerging infectious diseases that could affect the United States (U.S.) military. This mission is accomplished by orchestrating a global portfolio of surveillance projects, capacity-building efforts, outbreak investigations and training exercises. In 2009, this portfolio involved 39 funded partners, impacting 92 countries. This article discusses the current biosurveillance landscape, programmatic details of organization and implementation, and key contributions to force health protection and global public health in 2009.",2011 Mar 4,"['Russell, Kevin L', 'Rubenstein, Jennifer', 'Burke, Ronald L', 'Vest, Kelly G', 'Johns, Matthew C', 'Sanchez, Jose L', 'Meyer, William', 'Fukuda, Mark M', 'Blazes, David L']",BMC Public Health,,,True
6b18559c0c4de907cce17857d77321b52375ea36,PMC,Quantitative Subcellular Proteome and Secretome Profiling of Influenza A Virus-Infected Human Primary Macrophages,http://dx.doi.org/10.1371/journal.ppat.1001340,PMC3093355,21589892,CC BY,"Influenza A viruses are important pathogens that cause acute respiratory diseases and annual epidemics in humans. Macrophages recognize influenza A virus infection with their pattern recognition receptors, and are involved in the activation of proper innate immune response. Here, we have used high-throughput subcellular proteomics combined with bioinformatics to provide a global view of host cellular events that are activated in response to influenza A virus infection in human primary macrophages. We show that viral infection regulates the expression and/or subcellular localization of more than one thousand host proteins at early phases of infection. Our data reveals that there are dramatic changes in mitochondrial and nuclear proteomes in response to infection. We show that a rapid cytoplasmic leakage of lysosomal proteins, including cathepsins, followed by their secretion, contributes to inflammasome activation and apoptosis seen in the infected macrophages. Also, our results demonstrate that P2X(7) receptor and src tyrosine kinase activity are essential for inflammasome activation during influenza A virus infection. Finally, we show that influenza A virus infection is associated with robust secretion of different danger-associated molecular patterns (DAMPs) suggesting an important role for DAMPs in host response to influenza A virus infection. In conclusion, our high-throughput quantitative proteomics study provides important new insight into host-response against influenza A virus infection in human primary macrophages.",2011 May 12,"['Lietzén, Niina', 'Öhman, Tiina', 'Rintahaka, Johanna', 'Julkunen, Ilkka', 'Aittokallio, Tero', 'Matikainen, Sampsa', 'Nyman, Tuula A.']",PLoS Pathog,,,True
51f1e5b9a98b24f99b3d71b59b85c9bba957660c,PMC,Quantitative Subcellular Proteome and Secretome Profiling of Influenza A Virus-Infected Human Primary Macrophages,http://dx.doi.org/10.1371/journal.ppat.1001340,PMC3093355,21589892,CC BY,"Influenza A viruses are important pathogens that cause acute respiratory diseases and annual epidemics in humans. Macrophages recognize influenza A virus infection with their pattern recognition receptors, and are involved in the activation of proper innate immune response. Here, we have used high-throughput subcellular proteomics combined with bioinformatics to provide a global view of host cellular events that are activated in response to influenza A virus infection in human primary macrophages. We show that viral infection regulates the expression and/or subcellular localization of more than one thousand host proteins at early phases of infection. Our data reveals that there are dramatic changes in mitochondrial and nuclear proteomes in response to infection. We show that a rapid cytoplasmic leakage of lysosomal proteins, including cathepsins, followed by their secretion, contributes to inflammasome activation and apoptosis seen in the infected macrophages. Also, our results demonstrate that P2X(7) receptor and src tyrosine kinase activity are essential for inflammasome activation during influenza A virus infection. Finally, we show that influenza A virus infection is associated with robust secretion of different danger-associated molecular patterns (DAMPs) suggesting an important role for DAMPs in host response to influenza A virus infection. In conclusion, our high-throughput quantitative proteomics study provides important new insight into host-response against influenza A virus infection in human primary macrophages.",2011 May 12,"['Lietzén, Niina', 'Öhman, Tiina', 'Rintahaka, Johanna', 'Julkunen, Ilkka', 'Aittokallio, Tero', 'Matikainen, Sampsa', 'Nyman, Tuula A.']",PLoS Pathog,,,False
c5cbc7143785255c085b66a096790c84660dd1ec,PMC,Quantitative Subcellular Proteome and Secretome Profiling of Influenza A Virus-Infected Human Primary Macrophages,http://dx.doi.org/10.1371/journal.ppat.1001340,PMC3093355,21589892,CC BY,"Influenza A viruses are important pathogens that cause acute respiratory diseases and annual epidemics in humans. Macrophages recognize influenza A virus infection with their pattern recognition receptors, and are involved in the activation of proper innate immune response. Here, we have used high-throughput subcellular proteomics combined with bioinformatics to provide a global view of host cellular events that are activated in response to influenza A virus infection in human primary macrophages. We show that viral infection regulates the expression and/or subcellular localization of more than one thousand host proteins at early phases of infection. Our data reveals that there are dramatic changes in mitochondrial and nuclear proteomes in response to infection. We show that a rapid cytoplasmic leakage of lysosomal proteins, including cathepsins, followed by their secretion, contributes to inflammasome activation and apoptosis seen in the infected macrophages. Also, our results demonstrate that P2X(7) receptor and src tyrosine kinase activity are essential for inflammasome activation during influenza A virus infection. Finally, we show that influenza A virus infection is associated with robust secretion of different danger-associated molecular patterns (DAMPs) suggesting an important role for DAMPs in host response to influenza A virus infection. In conclusion, our high-throughput quantitative proteomics study provides important new insight into host-response against influenza A virus infection in human primary macrophages.",2011 May 12,"['Lietzén, Niina', 'Öhman, Tiina', 'Rintahaka, Johanna', 'Julkunen, Ilkka', 'Aittokallio, Tero', 'Matikainen, Sampsa', 'Nyman, Tuula A.']",PLoS Pathog,,,False
c6efc774a6d8d192e884408a84c8aa69ff385055,PMC,Quantitative Subcellular Proteome and Secretome Profiling of Influenza A Virus-Infected Human Primary Macrophages,http://dx.doi.org/10.1371/journal.ppat.1001340,PMC3093355,21589892,CC BY,"Influenza A viruses are important pathogens that cause acute respiratory diseases and annual epidemics in humans. Macrophages recognize influenza A virus infection with their pattern recognition receptors, and are involved in the activation of proper innate immune response. Here, we have used high-throughput subcellular proteomics combined with bioinformatics to provide a global view of host cellular events that are activated in response to influenza A virus infection in human primary macrophages. We show that viral infection regulates the expression and/or subcellular localization of more than one thousand host proteins at early phases of infection. Our data reveals that there are dramatic changes in mitochondrial and nuclear proteomes in response to infection. We show that a rapid cytoplasmic leakage of lysosomal proteins, including cathepsins, followed by their secretion, contributes to inflammasome activation and apoptosis seen in the infected macrophages. Also, our results demonstrate that P2X(7) receptor and src tyrosine kinase activity are essential for inflammasome activation during influenza A virus infection. Finally, we show that influenza A virus infection is associated with robust secretion of different danger-associated molecular patterns (DAMPs) suggesting an important role for DAMPs in host response to influenza A virus infection. In conclusion, our high-throughput quantitative proteomics study provides important new insight into host-response against influenza A virus infection in human primary macrophages.",2011 May 12,"['Lietzén, Niina', 'Öhman, Tiina', 'Rintahaka, Johanna', 'Julkunen, Ilkka', 'Aittokallio, Tero', 'Matikainen, Sampsa', 'Nyman, Tuula A.']",PLoS Pathog,,,False
f6daf6c68dd64802a28484b24191ff6e477d49b1,PMC,Quantitative Subcellular Proteome and Secretome Profiling of Influenza A Virus-Infected Human Primary Macrophages,http://dx.doi.org/10.1371/journal.ppat.1001340,PMC3093355,21589892,CC BY,"Influenza A viruses are important pathogens that cause acute respiratory diseases and annual epidemics in humans. Macrophages recognize influenza A virus infection with their pattern recognition receptors, and are involved in the activation of proper innate immune response. Here, we have used high-throughput subcellular proteomics combined with bioinformatics to provide a global view of host cellular events that are activated in response to influenza A virus infection in human primary macrophages. We show that viral infection regulates the expression and/or subcellular localization of more than one thousand host proteins at early phases of infection. Our data reveals that there are dramatic changes in mitochondrial and nuclear proteomes in response to infection. We show that a rapid cytoplasmic leakage of lysosomal proteins, including cathepsins, followed by their secretion, contributes to inflammasome activation and apoptosis seen in the infected macrophages. Also, our results demonstrate that P2X(7) receptor and src tyrosine kinase activity are essential for inflammasome activation during influenza A virus infection. Finally, we show that influenza A virus infection is associated with robust secretion of different danger-associated molecular patterns (DAMPs) suggesting an important role for DAMPs in host response to influenza A virus infection. In conclusion, our high-throughput quantitative proteomics study provides important new insight into host-response against influenza A virus infection in human primary macrophages.",2011 May 12,"['Lietzén, Niina', 'Öhman, Tiina', 'Rintahaka, Johanna', 'Julkunen, Ilkka', 'Aittokallio, Tero', 'Matikainen, Sampsa', 'Nyman, Tuula A.']",PLoS Pathog,,,False
50e8d64761dddc0b7ce037734d813eca7cd63701,PMC,"Alphacoronaviruses in New World Bats: Prevalence, Persistence, Phylogeny, and Potential for Interaction with Humans",http://dx.doi.org/10.1371/journal.pone.0019156,PMC3093381,21589915,CC0,"Bats are reservoirs for many different coronaviruses (CoVs) as well as many other important zoonotic viruses. We sampled feces and/or anal swabs of 1,044 insectivorous bats of 2 families and 17 species from 21 different locations within Colorado from 2007 to 2009. We detected alphacoronavirus RNA in bats of 4 species: big brown bats (Eptesicus fuscus), 10% prevalence; long-legged bats (Myotis volans), 8% prevalence; little brown bats (Myotis lucifugus), 3% prevalence; and western long-eared bats (Myotis evotis), 2% prevalence. Overall, juvenile bats were twice as likely to be positive for CoV RNA as adult bats. At two of the rural sampling sites, CoV RNAs were detected in big brown and long-legged bats during the three sequential summers of this study. CoV RNA was detected in big brown bats in all five of the urban maternity roosts sampled throughout each of the periods tested. Individually tagged big brown bats that were positive for CoV RNA and later sampled again all became CoV RNA negative. Nucleotide sequences in the RdRp gene fell into 3 main clusters, all distinct from those of Old World bats. Similar nucleotide sequences were found in amplicons from gene 1b and the spike gene in both a big-brown and a long-legged bat, indicating that a CoV may be capable of infecting bats of different genera. These data suggest that ongoing evolution of CoVs in bats creates the possibility of a continued threat for emergence into hosts of other species. Alphacoronavirus RNA was detected at a high prevalence in big brown bats in roosts in close proximity to human habitations (10%) and known to have direct contact with people (19%), suggesting that significant potential opportunities exist for cross-species transmission of these viruses. Further CoV surveillance studies in bats throughout the Americas are warranted.",2011 May 12,"['Osborne, Christina', 'Cryan, Paul M.', ""O'Shea, Thomas J."", 'Oko, Lauren M.', 'Ndaluka, Christina', 'Calisher, Charles H.', 'Berglund, Andrew D.', 'Klavetter, Mead L.', 'Bowen, Richard A.', 'Holmes, Kathryn V.', 'Dominguez, Samuel R.']",PLoS One,,,True
2e7571bccf8e71340eae54a7254aa136d0cbbcb3,PMC,Modeling the variations in pediatric respiratory syncytial virus seasonal epidemics,http://dx.doi.org/10.1186/1471-2334-11-105,PMC3094225,21510889,CC BY,"BACKGROUND: Seasonal respiratory syncytial virus (RSV) epidemics occur annually in temperate climates and result in significant pediatric morbidity and increased health care costs. Although RSV epidemics generally occur between October and April, the size and timing vary across epidemic seasons and are difficult to predict accurately. Prediction of epidemic characteristics would support management of resources and treatment. METHODS: The goals of this research were to examine the empirical relationships among early exponential growth rate, total epidemic size, and timing, and the utility of specific parameters in compartmental models of transmission in accounting for variation among seasonal RSV epidemic curves. RSV testing data from Primary Children's Medical Center were collected on children under two years of age (July 2001-June 2008). Simple linear regression was used explore the relationship between three epidemic characteristics (final epidemic size, days to peak, and epidemic length) and exponential growth calculated from four weeks of daily case data. A compartmental model of transmission was fit to the data and parameter estimated used to help describe the variation among seasonal RSV epidemic curves. RESULTS: The regression results indicated that exponential growth was correlated to epidemic characteristics. The transmission modeling results indicated that start time for the epidemic and the transmission parameter co-varied with the epidemic season. CONCLUSIONS: The conclusions were that exponential growth was somewhat empirically related to seasonal epidemic characteristics and that variation in epidemic start date as well as the transmission parameter over epidemic years could explain variation in seasonal epidemic size. These relationships are useful for public health, health care providers, and infectious disease researchers.",2011 Apr 21,"['Leecaster, Molly', 'Gesteland, Per', 'Greene, Tom', 'Walton, Nephi', 'Gundlapalli, Adi', 'Rolfs, Robert', 'Byington, Carrie', 'Samore, Matthew']",BMC Infect Dis,,,True
b34cc3d570e41a80c01088f73600357cf071a4da,PMC,Randomized placebo-controlled trial on azithromycin to reduce the morbidity of bronchiolitis in Indigenous Australian infants: rationale and protocol,http://dx.doi.org/10.1186/1745-6215-12-94,PMC3094234,21492416,CC BY,"BACKGROUND: Acute lower respiratory infections are the commonest cause of morbidity and potentially preventable mortality in Indigenous infants. Infancy is also a critical time for post-natal lung growth and development. Severe or repeated lower airway injury in very young children likely increases the likelihood of chronic pulmonary disorders later in life. Globally, bronchiolitis is the most common form of acute lower respiratory infections during infancy. Compared with non-Indigenous Australian infants, Indigenous infants have greater bacterial density in their upper airways and more severe bronchiolitis episodes. Our study tests the hypothesis that the anti-microbial and anti-inflammatory properties of azithromycin, improve the clinical outcomes of Indigenous Australian infants hospitalised with bronchiolitis. METHODS: We are conducting a dual centre, randomised, double-blind, placebo-controlled, parallel group trial in northern Australia. Indigenous infants (aged ≤ 24-months, expected number = 200) admitted to one of two regional hospitals (Darwin, Northern Territory and Townsville, Queensland) with a clinical diagnosis of bronchiolitis and fulfilling inclusion criteria are randomised (allocation concealed) to either azithromycin (30 mg/kg/dose) or placebo administered once weekly for three doses. Clinical data are recorded twice daily and nasopharyngeal swab are collected at enrolment and at the time of discharge from hospital. Primary outcomes are 'length of oxygen requirement' and 'duration of stay,' the latter based upon being judged as 'ready for respiratory discharge'. The main secondary outcome is readmission for a respiratory illness within 6-months of leaving hospital. Descriptive virological and bacteriological (including development of antibiotic resistance) data from nasopharyngeal samples will also be reported. DISCUSSION: Two published studies, both involving different patient populations and settings, as well as different macrolide antibiotics and treatment duration, have produced conflicting results. Our randomised, placebo-controlled trial of azithromycin in Indigenous infants hospitalised with bronchiolitis is designed to determine whether it can reduce short-term (and potentially long-term) morbidity from respiratory illness in Australian Indigenous infants who are at high risk of developing chronic respiratory illness. If azithromycin is efficacious in reducing the morbidly of Indigenous infants hospitalised with bronchiolitis, the intervention would lead to improved short term (and possibly long term) health benefits. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000326099",2011 Apr 14,"['Chang, Anne B', 'Grimwood, Keith', 'White, Andrew V', 'Maclennan, Carolyn', 'Sloots, Theo P', 'Sive, Alan', 'McCallum, Gabrielle B', 'Mackay, Ian M', 'Morris, Peter S']",Trials,,,True
a748ccbe075d2bc2223dae088c6014428992718d,PMC,Phylogenetic distribution and predominant genotype of the avian infectious bronchitis virus in China during 2008-2009,http://dx.doi.org/10.1186/1743-422X-8-184,PMC3094301,21510909,CC BY,"BACKGROUND: The nephropathogenic avian infectious bronchitis (IB) caused unprecedented economic losses to the commercial chicken industry of China in 2008-2009. To investigate the prevalence of nephropathogenic IB in China, eighty IBV isolates from different provinces during 2008-2009 were identified by dwarf embryo test and RT-PCR. RESULTS: The strains were mostly isolated in winter and spring with a wide age range of IB outbreaks, from 4 to 69 days. By the virus recovery trials, 70/80 of the strains resulted in the deaths or distresses of birds from nephritis. To learn more about the molecular evolutionary characteristics of the circulating field strains, the coding region of major spike 1 (S1) protein gene of these strains was RT-PCR amplified and sequenced. Compared to the published representative strains, nucleotides and amino acids sequence analysis indicated that the S1 genes of these strains and the reference strains displayed homologies ranging from 75.1% to 99.8% and from 73.1% to 99.8% respectively. S1 protein of the major pandemic strains contained 540 or 542 amino acids with the cleavage site of HRRRR or RRFRR. Phylogenetic analysis revealed that recent field isolates of IBV in China were mostly belonged to A2-branch (QXIBV-branch) and HN08-branch, only one isolate was belonged to Gray-branch and M41-branch respectively. Most of the 80 strains showed evolutionarily distant from vaccine strains. CONCLUSIONS: The results of this study suggested that nephropathogenic IBVs were mainly A2-like strains in China during 2008-2009.",2011 Apr 22,"['Ji, Jun', 'Xie, Jingwei', 'Chen, Feng', 'Shu, Dingming', 'Zuo, Kejing', 'Xue, Chunyi', 'Qin, Jianping', 'Li, Hongmei', 'Bi, Yingzuo', 'Ma, Jingyun', 'Xie, Qingmei']",Virol J,,,True
abf6f66d8e18b652d10944bb21e19debca5dc5e8,PMC,Analyzing Cytotoxic and Apoptogenic Properties of Scutellaria litwinowii Root Extract on Cancer Cell Lines,http://dx.doi.org/10.1093/ecam/nep214,PMC3094709,20028719,CC BY,"The Scutellaria species (Lamiaceae) is used as a source of flavonoids to treat a variety of diseases in traditional medicine. In spite of many reports about the cytotoxic and antitumor effects of some species of this genus, anticancer researches on one of the Iranian species S. litwinowii have not yet been conducted. The cytotoxic properties of total methanol extract of S. litwinowii and its fractions were investigated on different cancer cell lines including AGS, HeLa, MCF-7, PC12 and NIH 3T3. Meanwhile, the role of apoptosis in this toxicity was explored. The cells were cultured in DMEM medium and incubated with different concentrations of herb plant extracts. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1 peak). Scutellaria litwinowii inhibited the growth of malignant cells in a dose-dependent manner. Among solvent fractions of S. litwinowii, the methylene chloride fraction was found to be more toxic compared to other fractions. The IC(50) values of this fraction against AGS, HeLa, MCF-7 and PC12 cell lines after 24 h were determined, 121.2 ± 3.1, 40.9 ± 2.5, 115.9 ± 3.5 and 64.5 ± 3.4 μg/ml, respectively. Scutellaria litwinowii induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved in S. litwinowii toxicity. Scutellaria litwinowii exerts cytotoxic and proapototic effects in a variety of malignant cell lines and could be considered as a potential chemotherapeutic agent in cancer treatment.",2011 Mar 9,"['Tayarani-Najaran, Zahra', 'Emami, Seyed Ahmad', 'Asili, Javad', 'Mirzaei, Alireza', 'Mousavi, Seyed Hadi']",Evid Based Complement Alternat Med,,,True
61d48e2dee3bd05595403b3e5115d88d4e1dad5d,PMC,Potent Host-Directed Small-Molecule Inhibitors of Myxovirus RNA-Dependent RNA-Polymerases,http://dx.doi.org/10.1371/journal.pone.0020069,PMC3095640,21603574,CC BY,"Therapeutic targeting of host cell factors required for virus replication rather than of pathogen components opens new perspectives to counteract virus infections. Anticipated advantages of this approach include a heightened barrier against the development of viral resistance and a broadened pathogen target spectrum. Myxoviruses are predominantly associated with acute disease and thus are particularly attractive for this approach since treatment time can be kept limited. To identify inhibitor candidates, we have analyzed hit compounds that emerged from a large-scale high-throughput screen for their ability to block replication of members of both the orthomyxovirus and paramyxovirus families. This has returned a compound class with broad anti-viral activity including potent inhibition of different influenza virus and paramyxovirus strains. After hit-to-lead chemistry, inhibitory concentrations are in the nanomolar range in the context of immortalized cell lines and human PBMCs. The compound shows high metabolic stability when exposed to human S-9 hepatocyte subcellular fractions. Antiviral activity is host-cell species specific and most pronounced in cells of higher mammalian origin, supporting a host-cell target. While the compound induces a temporary cell cycle arrest, host mRNA and protein biosynthesis are largely unaffected and treated cells maintain full metabolic activity. Viral replication is blocked at a post-entry step and resembles the inhibition profile of a known inhibitor of viral RNA-dependent RNA-polymerase (RdRp) activity. Direct assessment of RdRp activity in the presence of the reagent reveals strong inhibition both in the context of viral infection and in reporter-based minireplicon assays. In toto, we have identified a compound class with broad viral target range that blocks host factors required for viral RdRp activity. Viral adaptation attempts did not induce resistance after prolonged exposure, in contrast to rapid adaptation to a pathogen-directed inhibitor of RdRp activity.",2011 May 16,"['Krumm, Stefanie A.', 'Ndungu, J. Maina', 'Yoon, Jeong-Joong', 'Dochow, Melanie', 'Sun, Aiming', 'Natchus, Michael', 'Snyder, James P.', 'Plemper, Richard K.']",PLoS One,,,True
cc8dfecfa5e0494957bbb094ce7989400d549027,PMC,Potent Host-Directed Small-Molecule Inhibitors of Myxovirus RNA-Dependent RNA-Polymerases,http://dx.doi.org/10.1371/journal.pone.0020069,PMC3095640,21603574,CC BY,"Therapeutic targeting of host cell factors required for virus replication rather than of pathogen components opens new perspectives to counteract virus infections. Anticipated advantages of this approach include a heightened barrier against the development of viral resistance and a broadened pathogen target spectrum. Myxoviruses are predominantly associated with acute disease and thus are particularly attractive for this approach since treatment time can be kept limited. To identify inhibitor candidates, we have analyzed hit compounds that emerged from a large-scale high-throughput screen for their ability to block replication of members of both the orthomyxovirus and paramyxovirus families. This has returned a compound class with broad anti-viral activity including potent inhibition of different influenza virus and paramyxovirus strains. After hit-to-lead chemistry, inhibitory concentrations are in the nanomolar range in the context of immortalized cell lines and human PBMCs. The compound shows high metabolic stability when exposed to human S-9 hepatocyte subcellular fractions. Antiviral activity is host-cell species specific and most pronounced in cells of higher mammalian origin, supporting a host-cell target. While the compound induces a temporary cell cycle arrest, host mRNA and protein biosynthesis are largely unaffected and treated cells maintain full metabolic activity. Viral replication is blocked at a post-entry step and resembles the inhibition profile of a known inhibitor of viral RNA-dependent RNA-polymerase (RdRp) activity. Direct assessment of RdRp activity in the presence of the reagent reveals strong inhibition both in the context of viral infection and in reporter-based minireplicon assays. In toto, we have identified a compound class with broad viral target range that blocks host factors required for viral RdRp activity. Viral adaptation attempts did not induce resistance after prolonged exposure, in contrast to rapid adaptation to a pathogen-directed inhibitor of RdRp activity.",2011 May 16,"['Krumm, Stefanie A.', 'Ndungu, J. Maina', 'Yoon, Jeong-Joong', 'Dochow, Melanie', 'Sun, Aiming', 'Natchus, Michael', 'Snyder, James P.', 'Plemper, Richard K.']",PLoS One,,,True
015729be3f439e9ef2033276a4ef14df8873dda9,PMC,Screening for Antiviral Activities of Isolated Compounds from Essential Oils,http://dx.doi.org/10.1093/ecam/nep187,PMC3096453,20008902,CC BY,"Essential oil of star anise as well as phenylpropanoids and sesquiterpenes, for example, trans-anethole, eugenol, β-eudesmol, farnesol, β-caryophyllene and β-caryophyllene oxide, which are present in many essential oils, were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. Antiviral activity was analyzed by plaque reduction assays and mode of antiviral action was determined by addition of the drugs to uninfected cells, to the virus prior to infection or to herpesvirus-infected cells. Star anise oil reduced viral infectivity by >99%, phenylpropanoids inhibited HSV infectivity by about 60–80% and sesquiterpenes suppressed herpes virus infection by 40–98%. Both, star anise essential oil and all isolated compounds exhibited anti-HSV-1 activity by direct inactivation of free virus particles in viral suspension assays. All tested drugs interacted in a dose-dependent manner with herpesvirus particles, thereby inactivating viral infectivity. Star anise oil, rich in trans-anethole, revealed a high selectivity index of 160 against HSV, whereas among the isolated compounds only β-caryophyllene displayed a high selectivity index of 140. The presence of β-caryophyllene in many essential oils might contribute strongly to their antiviral ability. These results indicate that phenylpropanoids and sesquiterpenes present in essential oils contribute to their antiviral activity against HSV.",2011 Feb 14,"['Astani, Akram', 'Reichling, Jürgen', 'Schnitzler, Paul']",Evid Based Complement Alternat Med,,,True
a4e72fc5914fe0e8387e5acce1aa3106705f7677,PMC,"Fever screening during the influenza (H1N1-2009) pandemic at Narita International Airport, Japan",http://dx.doi.org/10.1186/1471-2334-11-111,PMC3096599,21539735,CC BY,"BACKGROUND: Entry screening tends to start with a search for febrile international passengers, and infrared thermoscanners have been employed for fever screening in Japan. We aimed to retrospectively assess the feasibility of detecting influenza cases based on fever screening as a sole measure. METHODS: Two datasets were collected at Narita International Airport during the 2009 pandemic. The first contained confirmed influenza cases (n = 16) whose diagnosis took place at the airport during the early stages of the pandemic, and the second contained a selected and suspected fraction of passengers (self-reported or detected by an infrared thermoscanner; n = 1,049) screened from September 2009 to January 2010. The sensitivity of fever (38.0°C) for detecting H1N1-2009 was estimated, and the diagnostic performances of the infrared thermoscanners in detecting hyperthermia at cut-off levels of 37.5°C, 38.0°C and 38.5°C were also estimated. RESULTS: The sensitivity of fever for detecting H1N1-2009 cases upon arrival was estimated to be 22.2% (95% confidence interval: 0, 55.6) among nine confirmed H1N1-2009 cases, and 55.6% of the H1N1-2009 cases were under antipyretic medications upon arrival. The sensitivity and specificity of the infrared thermoscanners in detecting hyperthermia ranged from 50.8-70.4% and 63.6-81.7%, respectively. The positive predictive value appeared to be as low as 37.3-68.0%. CONCLUSIONS: The sensitivity of entry screening is a product of the sensitivity of fever for detecting influenza cases and the sensitivity of the infrared thermoscanners in detecting fever. Given the additional presence of confounding factors and unrestricted medications among passengers, reliance on fever alone is unlikely to be feasible as an entry screening measure.",2011 May 3,"['Nishiura, Hiroshi', 'Kamiya, Kazuko']",BMC Infect Dis,,,True
f3b7f4469ac01f1ce916d24172570c43c537627e,PMC,Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression,http://dx.doi.org/10.1371/journal.pone.0019705,PMC3096629,21611183,CC BY,"Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.",2011 May 17,"['Michaelis, Martin', 'Geiler, Janina', 'Naczk, Patrizia', 'Sithisarn, Patchima', 'Leutz, Anke', 'Doerr, Hans Wilhelm', 'Cinatl, Jindrich']",PLoS One,,,True
3aa13ec4d39637c70526a5965f8e9cdad76855f0,PMC,Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression,http://dx.doi.org/10.1371/journal.pone.0019705,PMC3096629,21611183,CC BY,"Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.",2011 May 17,"['Michaelis, Martin', 'Geiler, Janina', 'Naczk, Patrizia', 'Sithisarn, Patchima', 'Leutz, Anke', 'Doerr, Hans Wilhelm', 'Cinatl, Jindrich']",PLoS One,,,False
84be1a1130780982a380920c33e91c2d4b652d90,PMC,Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression,http://dx.doi.org/10.1371/journal.pone.0019705,PMC3096629,21611183,CC BY,"Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.",2011 May 17,"['Michaelis, Martin', 'Geiler, Janina', 'Naczk, Patrizia', 'Sithisarn, Patchima', 'Leutz, Anke', 'Doerr, Hans Wilhelm', 'Cinatl, Jindrich']",PLoS One,,,False
074e144c6cc7fb9de0cc550d3e777a0ccfa97007,PMC,Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression,http://dx.doi.org/10.1371/journal.pone.0019705,PMC3096629,21611183,CC BY,"Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.",2011 May 17,"['Michaelis, Martin', 'Geiler, Janina', 'Naczk, Patrizia', 'Sithisarn, Patchima', 'Leutz, Anke', 'Doerr, Hans Wilhelm', 'Cinatl, Jindrich']",PLoS One,,,False
68081e6d2768743855003f159baf5cb7ab59087d,PMC,A 5'-proximal Stem-loop Structure of 5' Untranslated Region of Porcine Reproductive and Respiratory Syndrome Virus Genome Is Key for Virus Replication,http://dx.doi.org/10.1186/1743-422X-8-172,PMC3096946,21496223,CC BY,"BACKGROUND: It has been well documented that the 5' untranslated region (5' UTR) of many positive-stranded RNA viruses contain key cis-acting regulatory sequences, as well as high-order structural elements. Little is known for such regulatory elements controlling porcine arterivirus replication. We investigated the roles of a conserved stem-loop 2 (SL2) that resides in the 5'UTR of the genome of a type II porcine reproductive and respiratory syndrome virus (PRRSV). RESULTS: We provided genetic evidences demonstrating that 1) the SL2 in type II PRRSV 5' UTR, N-SL2, could be structurally and functionally substituted by its counterpart in type I PRRSV, E-SL2; 2) the functionality of N-SL2 was dependent upon the G-C rich stem structure, while the ternary-loop size was irrelevant to RNA synthesis; 3) serial deletions showed that the stem integrity of N-SL2 was crucial for subgenomic mRNA synthesis; and 4) when extensive base-pairs in the stem region was deleted, an alternative N-SL2-like structure with different sequence was utilized for virus replication. CONCLUSION: Taken together, we concluded that the phylogenetically conserved SL2 in the 5' UTR was crucial for PRRSV virus replication, subgenomic mRNA synthesis in particular.",2011 Apr 15,"['Lu, Jiaqi', 'Gao, Fei', 'Wei, Zuzhang', 'Liu, Ping', 'Liu, Changlong', 'Zheng, Haihong', 'Li, Yanhua', 'Lin, Tao', 'Yuan, Shishan']",Virol J,,,True
4c59d82d87d20a5a5ab05c5c19895bda141167d4,PMC,Sometimes Sperm Whales (Physeter macrocephalus) Cannot Find Their Way Back to the High Seas: A Multidisciplinary Study on a Mass Stranding,http://dx.doi.org/10.1371/journal.pone.0019417,PMC3097202,21673789,CC BY,"BACKGROUND: Mass strandings of sperm whales (Physeter macrocephalus) remain peculiar and rather unexplained events, which rarely occur in the Mediterranean Sea. Solar cycles and related changes in the geomagnetic field, variations in water temperature and weather conditions, coast geographical features and human activities have been proposed as possible causes. In December 2009, a pod of seven male sperm whales stranded along the Adriatic coast of Southern Italy. This is the sixth instance from 1555 in this basin. METHODOLOGY/PRINCIPAL FINDINGS: Complete necropsies were performed on three whales whose bodies were in good condition, carrying out on sampled tissues histopathology, virology, bacteriology, parasitology, and screening of veins looking for gas emboli. Furthermore, samples for age determination, genetic studies, gastric content evaluation, stable isotopes and toxicology were taken from all the seven specimens. The animals were part of the same group and determined by genetic and photo-identification to be part of the Mediterranean population. Causes of death did not include biological agents, or the “gas and fat embolic syndrome”, associated with direct sonar exposure. Environmental pollutant tissue concentrations were relatively high, in particular organochlorinated xenobiotics. Gastric content and morphologic tissue examinations showed a prolonged starvation, which likely caused, at its turn, the mobilization of lipophilic contaminants from the adipose tissue. Chemical compounds subsequently entered the blood circulation and may have impaired immune and nervous functions. CONCLUSIONS/SIGNIFICANCE: A multi-factorial cause underlying this sperm whales' mass stranding is proposed herein based upon the results of postmortem investigations as well as of the detailed analyses of the geographical and historical background. The seven sperm whales took the same “wrong way” into the Adriatic Sea, a potentially dangerous trap for Mediterranean sperm whales. Seismic surveys should be also regarded as potential co-factors, even if no evidence of direct impact has been detected.",2011 May 18,"['Mazzariol, Sandro', 'Di Guardo, Giovanni', 'Petrella, Antonio', 'Marsili, Letizia', 'Fossi, Cristina M.', 'Leonzio, Claudio', 'Zizzo, Nicola', 'Vizzini, Salvatrice', 'Gaspari, Stefania', 'Pavan, Gianni', 'Podestà, Michela', 'Garibaldi, Fulvio', 'Ferrante, Margherita', 'Copat, Chiara', 'Traversa, Donato', 'Marcer, Federica', 'Airoldi, Sabina', 'Frantzis, Alexandros', 'De Bernaldo Quirós, Yara', 'Cozzi, Bruno', 'Fernández, Antonio']",PLoS One,,,True
39b557ab42e265c37acee079b474c73708f197c7,PMC,Insight into the Interaction of Metal Ions with TroA from Streptococcus suis,http://dx.doi.org/10.1371/journal.pone.0019510,PMC3097204,21611125,CC BY,"BACKGROUND: The scavenging ability of sufficient divalent metal ions is pivotal for pathogenic bacteria to survive in the host. ATP-binding cassette (ABC)-type metal transporters provide a considerable amount of different transition metals for bacterial growth. TroA is a substrate binding protein for uptake of multiple metal ions. However, the function and structure of the TroA homologue from the epidemic Streptococcus suis isolates (SsTroA) have not been characterized. METHODOLOGY/PRINCIPAL FINDINGS: Here we determined the crystal structure of SsTroA from a highly pathogenic streptococcal toxic shock syndrome (STSS)-causing Streptococcus suis in complex with zinc. Inductively coupled plasma mass spectrometry (ICP-MS) analysis revealed that apo-SsTroA binds Zn(2+) and Mn(2+). Both metals bind to SsTroA with nanomolar affinity and stabilize the protein against thermal unfolding. Zn(2+) and Mn(2+) induce distinct conformational changes in SsTroA compared with the apo form as confirmed by both circular dichroism (CD) and nuclear magnetic resonance (NMR) spectra. NMR data also revealed that Zn(2+)/Mn(2+) bind to SsTroA in either the same site or an adjacent region. Finally, we found that the folding of the metal-bound protein is more compact than the corresponding apoprotein. CONCLUSIONS/SIGNIFICANCE: Our findings reveal a mechanism for uptake of metal ions in S. suis and this mechanism provides a reasonable explanation as to how SsTroA operates in metal transport.",2011 May 18,"['Zheng, Beiwen', 'Zhang, Qiangmin', 'Gao, Jia', 'Han, Huiming', 'Li, Ming', 'Zhang, Jingren', 'Qi, Jianxun', 'Yan, Jinghua', 'Gao, George F.']",PLoS One,,,True
aa69482e261bf1d6546491ba52991ea1ac3402a1,PMC,"Identification of Mycobacterium tuberculosis-Specific Th1, Th17 and Th22 Cells Using the Expression of CD40L in Tuberculous Pleurisy",http://dx.doi.org/10.1371/journal.pone.0020165,PMC3097245,21625607,CC BY,"Important advances have been made in the immunodiagnosis of tuberculosis (TB) based on the detection of Mycobacterium tuberculosis (MTB)-specific T cells. However, the sensitivity and specificity of the immunological approach are relatively low because there are no specific markers for antigen-specific Th cells, and some of the Th cells that do not produce cytokines can be overlooked using this approach. In this study, we found that MTB-specific peptides of ESAT-6/CFP-10 can stimulate the expression of CD40L specifically in CD4(+) T cells but not other cells from pleural fluid cells (PFCs) in patients with tuberculous pleurisy (TBP). CD4(+)CD40L(+) but not CD4(+)CD40L(−) T cells express IFN-γ, IL-2, TNF-α, IL-17 or IL-22 after stimulation with MTB-specific peptides. In addition, CD4(+)CD40L(+) T cells were found to be mostly polyfunctional T cells that simultaneously produce IFN-γ, IL-2 and TNF-α and display an effector or effector memory phenotype (CD45RA(−)CD45RO(+)CCR7(−)CD62L(−)ICOS(−)). To determine the specificity of CD4(+)CD40L(+) T cells, we incubated PFCs with ESTA-6/CFP-10 peptides and sorted live CD4(+)CD40L(+) and CD4(+)CD40L(−) T cells by flow cytometry. We further demonstrated that sorted CD4(+)CD40L(+), but not CD4(+)CD40L(−) fractions, principally produced IFN-γ, IL-2, TNF-α, IL-17 and IL-22 following restimulation with ESTA-6/CFP-10 peptides. Taken together, our data indicate that the expression of CD40L on MTB-specific CD4(+) T cells could be a good marker for the evaluation and isolation of MTB-specific Th cells and might also be useful in the diagnosis of TB.",2011 May 18,"['Li, Li', 'Qiao, Dan', 'Fu, Xiaoying', 'Lao, Suihua', 'Zhang, Xianlan', 'Wu, Changyou']",PLoS One,,,True
9dc767a57df46887166f86194ad8fd2d94b6dba5,PMC,Chest imaging features of patients afflicted with Influenza A (H1N1) in a Malaysian tertiary referral centre,http://dx.doi.org/10.2349/biij.6.4.e35,PMC3097804,21611071,CC BY,"This is a retrospective descriptive study of the chest imaging findings of 118 patients with confirmed A(H1N1) in a tertiary referral centre. About 42% of the patients had positive initial chest radiographic (CXR) findings. The common findings were bi-basal air-space opacities and perihilar reticular and alveolar infiltrates. In select cases, high-resolution computed tomography (CT) imaging showed ground-glass change with some widespread reticular changes and atelectasis.",2010 Oct 1,"['Bux, SI', 'Mohd. Ramli, N', 'Ahmad Sarji, S', 'Kamarulzaman, A']",Biomed Imaging Interv J,,,True
e086d4275f9420065465a39f78c29bd36a5796d3,PMC,Using simple artificial intelligence methods for predicting amyloidogenesis in antibodies,http://dx.doi.org/10.1186/1471-2105-11-79,PMC3098112,20144194,CC BY,"BACKGROUND: All polypeptide backbones have the potential to form amyloid fibrils, which are associated with a number of degenerative disorders. However, the likelihood that amyloidosis would actually occur under physiological conditions depends largely on the amino acid composition of a protein. We explore using a naive Bayesian classifier and a weighted decision tree for predicting the amyloidogenicity of immunoglobulin sequences. RESULTS: The average accuracy based on leave-one-out (LOO) cross validation of a Bayesian classifier generated from 143 amyloidogenic sequences is 60.84%. This is consistent with the average accuracy of 61.15% for a holdout test set comprised of 103 AM and 28 non-amyloidogenic sequences. The LOO cross validation accuracy increases to 81.08% when the training set is augmented by the holdout test set. In comparison, the average classification accuracy for the holdout test set obtained using a decision tree is 78.64%. Non-amyloidogenic sequences are predicted with average LOO cross validation accuracies between 74.05% and 77.24% using the Bayesian classifier, depending on the training set size. The accuracy for the holdout test set was 89%. For the decision tree, the non-amyloidogenic prediction accuracy is 75.00%. CONCLUSIONS: This exploratory study indicates that both classification methods may be promising in providing straightforward predictions on the amyloidogenicity of a sequence. Nevertheless, the number of available sequences that satisfy the premises of this study are limited, and are consequently smaller than the ideal training set size. Increasing the size of the training set clearly increases the accuracy, and the expansion of the training set to include not only more derivatives, but more alignments, would make the method more sound. The accuracy of the classifiers may also be improved when additional factors, such as structural and physico-chemical data, are considered. The development of this type of classifier has significant applications in evaluating engineered antibodies, and may be adapted for evaluating engineered proteins in general.",2010 Feb 8,"['David, Maria Pamela C', 'Concepcion, Gisela P', 'Padlan, Eduardo A']",BMC Bioinformatics,,,True
3240298a10e4834230eabe0b7cb5a728c00779af,PMC,Murine immune responses to a Plasmodium vivax-derived chimeric recombinant protein expressed in Brassica napus,http://dx.doi.org/10.1186/1475-2875-10-106,PMC3098821,21529346,CC BY,"BACKGROUND: To develop a plant-based vaccine against Plasmodium vivax, two P. vivax candidate proteins were chosen. First, the merozoite surface protein-1 (MSP-1), a major asexual blood stage antigen that is currently considered a strong vaccine candidate. Second, the circumsporozoite protein (CSP), a component of sporozoites that contains a B-cell epitope. METHODS: A synthetic chimeric recombinant 516 bp gene encoding containing PvMSP-1, a Pro-Gly linker motif, and PvCSP was synthesized; the gene, named MLC, encoded a total of 172 amino acids. The recombinant gene was modified with regard to codon usage to optimize gene expression in Brassica napus. The Ti plasmid inducible gene transfer system was used for MLC chimeric recombinant gene expression in B. napus. Gene expression was confirmed by polymerase chain reaction (PCR), beta-glucuronidase reporter gene (GUS) assay, and Western blot. RESULTS: The MLC chimeric recombinant protein expressed in B. napus had a molecular weight of approximately 25 kDa. It exhibited a clinical sensitivity of 84.21% (n = 38) and a clinical specificity of 100% (n = 24) as assessed by enzyme-linked immunosorbent assay (ELISA). Oral immunization of BALB/c mice with MLC chimeric recombinant protein successfully induced antigen-specific IgG1 production. Additionally, the Th1-related cytokines IL-12 (p40), TNF, and IFN-γ were significantly increased in the spleens of the BALB/c mice. CONCLUSIONS: The chimeric MLC recombinant protein produced in B. napus has potential as both as an antigen for diagnosis and as a valuable vaccine candidate for oral immunization against vivax malaria.",2011 Apr 29,"['Lee, Choonghee', 'Kim, Hyung-Hwan', 'Mi Choi, Kyung', 'Won Chung, Kyung', 'Choi, Yien Kyoung', 'Jang, Mi Jung', 'Kim, Tong-Soo', 'Chung, Nam-Jun', 'Rhie, Ho-Gun', 'Lee, Ho-Sa', 'Sohn, Youngjoo', 'Kim, Hyuck', 'Lee, Sung-Jae', 'Lee, Hyeong-Woo']",Malar J,,,True
0638a299934da797243f6f35a516e172a38466a4,PMC,Diffuse Alveolar Damage: A Common Phenomenon in Progressive Interstitial Lung Disorders,http://dx.doi.org/10.1155/2011/531302,PMC3099744,21637367,CC BY,"It has become obvious that several interstitial lung diseases, and even viral lung infections, can progress rapidly, and exhibit similar features in their lung morphology. The final histopathological feature, common in these lung disorders, is diffuse alveolar damage (DAD). The histopathology of DAD is considered to represent end stage phenomenon in acutely behaving interstitial pneumonias, such as acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic pulmonary fibrosis (IPF). Acute worsening and DAD may occur also in patients with nonspecific interstitial pneumonias (NSIPs), and even in severe viral lung infections where there is DAD histopathology in the lung. A better understanding of the mechanisms underlying the DAD reaction is needed to clarify the treatment for these serious lung diseases. There is an urgent need for international efforts for studying DAD-associated lung diseases, since the prognosis of these patients has been and is still dismal.",2011 Nov 2,"['Kaarteenaho, Riitta', 'Kinnula, Vuokko L.']",Pulm Med,,,True
aec923adf0e16d218315a3083aaa71fb9ddb8b39,PMC,Temporal Anomalies in Immunological Gene Expression in a Time Series of Wild Mice: Signature of an Epidemic?,http://dx.doi.org/10.1371/journal.pone.0020070,PMC3100328,21629775,CC BY,"Although the ecological importance of coinfection is increasingly recognized, analyses of microbial pathogen dynamics in wildlife usually focus on an ad hoc subset of the species present due to technological limitations on detection. Here we demonstrate the use of expression profiles for immunological genes (pattern recognition receptors, cytokines and transcription factors) as a means to identify, without preconception, the likelihood of important acute microbial infections in wildlife. Using a wood mouse population in the UK as a model we identified significant temporal clusters of individuals with extreme expression of immunological mediators across multiple loci, typical of an acute microbial infection. These clusters were circumstantially associated with demographic perturbation in the summertime wood mouse population. Animals in one cluster also had significantly higher individual macroparasite burdens than contemporaries with “normal” expression patterns. If the extreme transcriptional profiles observed are induced by an infectious agent then this implicates macroparasites as a possible player in mediating individual susceptibility or resilience to infection. The form of survey described here, combined with next generation nucleic acids sequencing methods for the broad detection of microbial infectious agents in individuals with anomalous immunological transcriptional profiles, could be a powerful tool for revealing unrecognized, ecologically important infectious agents circulating in wildlife populations.",2011 May 23,"['Friberg, Ida M.', 'Lowe, Ann', 'Ralli, Catriona', 'Bradley, Janette E.', 'Jackson, Joseph A.']",PLoS One,,,True
06d734de60efb9ac8c98cd02be9f667d0c535fb0,PMC,Propagation of Respiratory Aerosols by the Vuvuzela,http://dx.doi.org/10.1371/journal.pone.0020086,PMC3100331,21629778,CC BY,"Vuvuzelas, the plastic blowing horns used by sports fans, recently achieved international recognition during the FIFA World Cup soccer tournament in South Africa. We hypothesised that vuvuzelas might facilitate the generation and dissemination of respiratory aerosols. To investigate the quantity and size of aerosols emitted when the instrument is played, eight healthy volunteers were asked to blow a vuvuzela. For each individual the concentration of particles in expelled air was measured using a six channel laser particle counter and the duration of blowing and velocity of air leaving the vuvuzela were recorded. To allow comparison with other activities undertaken at sports events each individual was also asked to shout and the measurements were repeated while using a paper cone to confine the exhaled air. Triplicate measurements were taken for each individual. The mean peak particle counts were 658×10(3) per litre for the vuvuzela and 3.7×10(3) per litre for shouting, representing a mean log(10) difference of 2.20 (95% CI: 2.03,2.36; p<0.001). The majority (>97%) of particles captured from either the vuvuzela or shouting were between 0.5 and 5 microns in diameter. Mean peak airflows recorded for the vuvuzela and shouting were 6.1 and 1.8 litres per second respectively. We conclude that plastic blowing horns (vuvuzelas) have the capacity to propel extremely large numbers of aerosols into the atmosphere of a size able to penetrate the lower lung. Some respiratory pathogens are spread via contaminated aerosols emitted by infected persons. Further investigation is required to assess the potential of the vuvuzela to contribute to the transmission of aerosol borne diseases. We recommend, as a precautionary measure, that people with respiratory infections should be advised not to blow their vuvuzela in enclosed spaces and where there is a risk of infecting others.",2011 May 23,"['Lai, Ka-Man', 'Bottomley, Christian', 'McNerney, Ruth']",PLoS One,,,True
049d68aa5279d807e4125c33a3d563f6df987cb4,PMC,Gradual Increase of High Mobility Group Protein B1 in the Lungs after the Onset of Acute Exacerbation of Idiopathic Pulmonary Fibrosis,http://dx.doi.org/10.1155/2011/916486,PMC3100576,21637372,CC BY,"The pathogenesis of acute exacerbation of idiopathic pulmonary fibrosis (IPF) remains to be elucidated. To evaluate the roles of inflammatory mediators in acute exacerbation, the concentrations of high mobility group protein B1 (HMGB1), a chief mediator of acute lung injury, and 18 inflammatory cytokines were measured in the bronchoalveolar lavage fluid, serially sampled from seven IPF patients after the onset of acute exacerbation. HMGB1 gradually increased in the alveolar fluid after the onset of acute exacerbation, in positive correlation with monocytes chemotactic protein-1 (MCP-1), a potent fibrogenic mediator. In the lung tissues of eight IPF patients autopsied after acute exacerbation, intense cytoplasmic staining for HMGB1 was observed in the alveolar epithelial cells in alveolar capillary augmented lesions, where the capillary endothelial cells remarkably reduced the expression of thrombomodulin, an intrinsic antagonist of HMGB1. These results suggest pathogenic roles for HMGB1 and MCP-1 in the late phase of acute exacerbation of IPF.",2011 Feb 21,"['Ebina, Masahito', 'Taniguchi, Hiroyuki', 'Miyasho, Taku', 'Yamada, Shingo', 'Shibata, Naoko', 'Ohta, Hiromitsu', 'Hisata, Shu', 'Ohkouchi, Shinya', 'Tamada, Tsutomu', 'Nishimura, Hidekazu', 'Ishizaka, Akitoshi', 'Maruyama, Ikuro', 'Okada, Yoshinori', 'Takashi, Kondo', 'Nukiwa, Toshihiro']",Pulm Med,,,True
38d4184fcc07afbf2bd269491da88687764e86f0,PMC,Protein Microarrays and Biomarkers of Infectious Disease,http://dx.doi.org/10.3390/ijms11125165,PMC3100839,21614200,CC BY,"Protein microarrays are powerful tools that are widely used in systems biology research. For infectious diseases, proteome microarrays assembled from proteins of pathogens will play an increasingly important role in discovery of diagnostic markers, vaccines, and therapeutics. Distinct formats of protein microarrays have been developed for different applications, including abundance-based and function-based methods. Depending on the application, design issues should be considered, such as the need for multiplexing and label or label free detection methods. New developments, challenges, and future demands in infectious disease research will impact the application of protein microarrays for discovery and validation of biomarkers.",2010 Dec 16,"['Natesan, Mohan', 'Ulrich, Robert G.']",Int J Mol Sci,,,True
94a4251b88b47417be1ebffe98259c1d4c1e0b36,PMC,"Spliced Leader RNAs, Mitochondrial Gene Frameshifts and Multi-Protein Phylogeny Expand Support for the Genus Perkinsus as a Unique Group of Alveolates",http://dx.doi.org/10.1371/journal.pone.0019933,PMC3101222,21629701,CC BY,"The genus Perkinsus occupies a precarious phylogenetic position. To gain a better understanding of the relationship between perkinsids, dinoflagellates and other alveolates, we analyzed the nuclear-encoded spliced-leader (SL) RNA and mitochondrial genes, intron prevalence, and multi-protein phylogenies. In contrast to the canonical 22-nt SL found in dinoflagellates (DinoSL), P. marinus has a shorter (21-nt) and a longer (22-nt) SL with slightly different sequences than DinoSL. The major SL RNA transcripts range in size between 80–83 nt in P. marinus, and ∼83 nt in P. chesapeaki, significantly larger than the typical ≤56-nt dinoflagellate SL RNA. In most of the phylogenetic trees based on 41 predicted protein sequences, P. marinus branched at the base of the dinoflagellate clade that included the ancient taxa Oxyrrhis and Amoebophrya, sister to the clade of apicomplexans, and in some cases clustered with apicomplexans as a sister to the dinoflagellate clade. Of 104 Perkinsus spp. genes examined 69.2% had introns, a higher intron prevalence than in dinoflagellates. Examination of Perkinsus spp. mitochondrial cytochrome B and cytochrome C oxidase subunit I genes and their cDNAs revealed no mRNA editing, but these transcripts can only be translated when frameshifts are introduced at every AGG and CCC codon as if AGGY codes for glycine and CCCCU for proline. These results, along with the presence of the numerous uncharacterized ‘marine alveolate group I' and Perkinsus-like lineages separating perkinsids from core dinoflagellates, expand support for the affiliation of the genus Perkinsus with an independent lineage (Perkinsozoa) positioned between the phyla of Apicomplexa and Dinoflagellata.",2011 May 24,"['Zhang, Huan', 'Campbell, David A.', 'Sturm, Nancy R.', 'Dungan, Christopher F.', 'Lin, Senjie']",PLoS One,,,True
e65736745475f7a3bab0f310edb593acc50528b7,PMC,Crystal Structure and Functional Analysis of the SARS-Coronavirus RNA Cap 2′-O-Methyltransferase nsp10/nsp16 Complex,http://dx.doi.org/10.1371/journal.ppat.1002059,PMC3102710,21637813,CC BY,"Cellular and viral S-adenosylmethionine-dependent methyltransferases are involved in many regulated processes such as metabolism, detoxification, signal transduction, chromatin remodeling, nucleic acid processing, and mRNA capping. The Severe Acute Respiratory Syndrome coronavirus nsp16 protein is a S-adenosylmethionine-dependent (nucleoside-2′-O)-methyltransferase only active in the presence of its activating partner nsp10. We report the nsp10/nsp16 complex structure at 2.0 Å resolution, which shows nsp10 bound to nsp16 through a ∼930 Å(2) surface area in nsp10. Functional assays identify key residues involved in nsp10/nsp16 association, and in RNA binding or catalysis, the latter likely through a SN2-like mechanism. We present two other crystal structures, the inhibitor Sinefungin bound in the S-adenosylmethionine binding pocket and the tighter complex nsp10(Y96F)/nsp16, providing the first structural insight into the regulation of RNA capping enzymes in (+)RNA viruses.",2011 May 26,"['Decroly, Etienne', 'Debarnot, Claire', 'Ferron, François', 'Bouvet, Mickael', 'Coutard, Bruno', 'Imbert, Isabelle', 'Gluais, Laure', 'Papageorgiou, Nicolas', 'Sharff, Andrew', 'Bricogne, Gérard', 'Ortiz-Lombardia, Miguel', 'Lescar, Julien', 'Canard, Bruno']",PLoS Pathog,,,True
e88b28b3664d30889a0161ddee188c48897a3bee,PMC,"SARS-CoV 9b Protein Diffuses into Nucleus, Undergoes Active Crm1 Mediated Nucleocytoplasmic Export and Triggers Apoptosis When Retained in the Nucleus",http://dx.doi.org/10.1371/journal.pone.0019436,PMC3103500,21637748,CC BY,"BACKGROUND: 9b is an accessory protein of the SARS-CoV. It is a small protein of 98 amino acids and its structure has been solved recently. 9b is known to localize in the extra-nuclear region and has been postulated to possess a nuclear export signal (NES), however the role of NES in 9b functioning is not well understood. PRINCIPAL FINDINGS/METHODOLOGY: In this report, we demonstrate that 9b in the absence of any nuclear localization signal (NLS) enters the nucleus by passive transport. Using various cell cycle inhibitors, we have shown that the nuclear entry of 9b is independent of the cell cycle. Further, we found that 9b interacts with the cellular protein Crm1 and gets exported out of the nucleus using an active NES. We have also revealed that this NES activity influences the half-life of 9b and affects host cell death. We found that an export signal deficient SARS-CoV 9b protein induces apoptosis in transiently transfected cells and showed elevated caspase-3 activity. CONCLUSION/SIGNIFICANCE: Here, we showed that nuclear shuttling of 9b and its interaction with Crm1 are essential for the proper degradation of 9b and blocking the nuclear export of this protein induces apoptosis. This phenomenon may be critical in providing a novel role to the 9b accessory protein of SARS-CoV.",2011 May 27,"['Sharma, Kulbhushan', 'Åkerström, Sara', 'Sharma, Anuj Kumar', 'Chow, Vincent T. K.', 'Teow, Shumein', 'Abrenica, Bernard', 'Booth, Stephanie A.', 'Booth, Timothy F.', 'Mirazimi, Ali', 'Lal, Sunil K.']",PLoS One,,,True
4ca552dd7e18609e57226f02001bf51bec3000bb,PMC,A New Approach to Monitoring Dengue Activity,http://dx.doi.org/10.1371/journal.pntd.0001215,PMC3104030,21647309,CC0,,2011 May 31,"['Madoff, Lawrence C.', 'Fisman, David N.', 'Kass-Hout, Taha']",PLoS Negl Trop Dis,,,True
db493d400b682be0385bd1ff034fa718d0c398cb,PMC,Maternal Influenza Immunization and Reduced Likelihood of Prematurity and Small for Gestational Age Births: A Retrospective Cohort Study,http://dx.doi.org/10.1371/journal.pmed.1000441,PMC3104979,21655318,CC BY,"BACKGROUND: Infections during pregnancy have the potential to adversely impact birth outcomes. We evaluated the association between receipt of inactivated influenza vaccine during pregnancy and prematurity and small for gestational age (SGA) births. METHODS AND FINDINGS: We conducted a cohort analysis of surveillance data from the Georgia (United States) Pregnancy Risk Assessment Monitoring System. Among 4,326 live births between 1 June 2004 and 30 September 2006, maternal influenza vaccine information was available for 4,168 (96.3%). The primary intervention evaluated in this study was receipt of influenza vaccine during any trimester of pregnancy. The main outcome measures were prematurity (gestational age at birth <37 wk) and SGA (birth weight <10th percentile for gestational age). Infants who were born during the putative influenza season (1 October–31 May) and whose mothers were vaccinated against influenza during pregnancy were less likely to be premature compared to infants of unvaccinated mothers born in the same period (adjusted odds ratio [OR] = 0.60; 95% CI, 0.38–0.94). The magnitude of association between maternal influenza vaccine receipt and reduced likelihood of prematurity increased during the period of at least local influenza activity (adjusted OR = 0.44; 95% CI, 0.26–0.73) and was greatest during the widespread influenza activity period (adjusted OR = 0.28; 95% CI, 0.11–0.74). Compared with newborns of unvaccinated women, newborns of vaccinated mothers had 69% lower odds of being SGA (adjusted OR = 0.31; 95% CI, 0.13–0.75) during the period of widespread influenza activity. The adjusted and unadjusted ORs were not significant for the pre-influenza activity period. CONCLUSIONS: This study demonstrates an association between immunization with the inactivated influenza vaccine during pregnancy and reduced likelihood of prematurity during local, regional, and widespread influenza activity periods. However, no associations were found for the pre-influenza activity period. Moreover, during the period of widespread influenza activity there was an association between maternal receipt of influenza vaccine and reduced likelihood of SGA birth. Please see later in the article for the Editors' Summary",2011 May 31,"['Omer, Saad B.', 'Goodman, David', 'Steinhoff, Mark C.', 'Rochat, Roger', 'Klugman, Keith P.', 'Stoll, Barbara J.', 'Ramakrishnan, Usha']",PLoS Med,,,True
a3bd2c7d348548cb21d4e9f4eb63ac51ea015e10,PMC,"Access to a polymerase chain reaction assay method targeting 13 respiratory viruses can reduce antibiotics: a randomised, controlled trial",http://dx.doi.org/10.1186/1741-7015-9-44,PMC3108322,21521505,CC BY,"BACKGROUND: Viral respiratory infections are common worldwide and range from completely benign disease to life-threatening illness. Symptoms can be unspecific, and an etiologic diagnosis is rarely established because of a lack of suitable diagnostic tools. Improper use of antibiotics is common in this setting, which is detrimental in light of the development of bacterial resistance. It has been suggested that the use of diagnostic tests could reduce antibiotic prescription rates. The objective of this study was to evaluate whether access to a multiplex polymerase chain reaction (PCR) assay panel for etiologic diagnosis of acute respiratory tract infections (ARTIs) would have an impact on antibiotic prescription rate in primary care clinical settings. METHODS: Adult patients with symptoms of ARTI were prospectively included. Nasopharyngeal and throat swabs were analysed by using a multiplex real-time PCR method targeting thirteen viruses and two bacteria. Patients were recruited at 12 outpatient units from October 2006 through April 2009, and samples were collected on the day of inclusion (initial visit) and after 10 days (follow-up visit). Patients were randomised in an open-label treatment protocol to receive a rapid or delayed result (on the following day or after eight to twelve days). The primary outcome measure was the antibiotic prescription rate at the initial visit, and the secondary outcome was the total antibiotic prescription rate during the study period. RESULTS: A total sample of 447 patients was randomised. Forty-one were excluded, leaving 406 patients for analysis. In the group of patients randomised for a rapid result, 4.5% (9 of 202) of patients received antibiotics at the initial visit, compared to 12.3% (25 of 204) (P = 0.005) of patients in the delayed result group. At follow-up, there was no significant difference between the groups: 13.9% (28 of 202) in the rapid result group and 17.2% (35 of 204) in the delayed result group (P = 0.359), respectively. CONCLUSIONS: Access to a rapid method for etiologic diagnosis of ARTIs may reduce antibiotic prescription rates at the initial visit in an outpatient setting. To sustain this effect, however, it seems necessary to better define how to follow and manage the patient according to the result of the test, which warrants further investigation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01133782.",2011 Apr 26,"['Brittain-Long, Robin', 'Westin, Johan', 'Olofsson, Sigvard', 'Lindh, Magnus', 'Andersson, Lars-Magnus']",BMC Med,,,True
3acb357dc20a411ef495ab53d242e5a0454cd1fb,PMC,Standardization of Methods for Early Diagnosis and On-Site Treatment of High-Altitude Pulmonary Edema,http://dx.doi.org/10.1155/2011/190648,PMC3109313,21660284,CC BY,"High-altitude pulmonary edema (HAPE) is a life-threatening disease of high altitude that often affects nonacclimatized apparently healthy individuals who rapidly ascend to high altitude. Early detection, early diagnosis, and early treatment are essential to maintain the safety of people who ascend to high altitude, such as construction workers and tourists. In this paper, I discuss various methods and criteria that can be used for the early diagnosis and prediction of HAPE. I also discuss the preventive strategies and options for on-site treatment. My objective is to improve the understanding of HAPE and to highlight the need for prevention, early diagnosis, and early treatment of HAPE to improve the safety of individuals ascending to high altitude.",2011 Jun 1,"Zhou, Qiquan",Pulm Med,,,True
c4127920bfadc5eaa2ff7d2180f8e1de7e3a673a,PMC,"Temporal Analysis of the Honey Bee Microbiome Reveals Four Novel Viruses and Seasonal Prevalence of Known Viruses, Nosema, and Crithidia",http://dx.doi.org/10.1371/journal.pone.0020656,PMC3110205,21687739,CC BY,"Honey bees (Apis mellifera) play a critical role in global food production as pollinators of numerous crops. Recently, honey bee populations in the United States, Canada, and Europe have suffered an unexplained increase in annual losses due to a phenomenon known as Colony Collapse Disorder (CCD). Epidemiological analysis of CCD is confounded by a relative dearth of bee pathogen field studies. To identify what constitutes an abnormal pathophysiological condition in a honey bee colony, it is critical to have characterized the spectrum of exogenous infectious agents in healthy hives over time. We conducted a prospective study of a large scale migratory bee keeping operation using high-frequency sampling paired with comprehensive molecular detection methods, including a custom microarray, qPCR, and ultra deep sequencing. We established seasonal incidence and abundance of known viruses, Nosema sp., Crithidia mellificae, and bacteria. Ultra deep sequence analysis further identified four novel RNA viruses, two of which were the most abundant observed components of the honey bee microbiome (∼10(11) viruses per honey bee). Our results demonstrate episodic viral incidence and distinct pathogen patterns between summer and winter time-points. Peak infection of common honey bee viruses and Nosema occurred in the summer, whereas levels of the trypanosomatid Crithidia mellificae and Lake Sinai virus 2, a novel virus, peaked in January.",2011 Jun 7,"['Runckel, Charles', 'Flenniken, Michelle L.', 'Engel, Juan C.', 'Ruby, J. Graham', 'Ganem, Donald', 'Andino, Raul', 'DeRisi, Joseph L.']",PLoS One,,,True
0c0806be80c60f0e61f084f12ed847c265fc1d68,PMC,Evaluation of Coseasonality of Influenza and Invasive Pneumococcal Disease: Results from Prospective Surveillance,http://dx.doi.org/10.1371/journal.pmed.1001042,PMC3110256,21687693,CC BY,"BACKGROUND: The wintertime co-occurrence of peaks in influenza and invasive pneumococcal disease (IPD) is well documented, but how and whether wintertime peaks caused by these two pathogens are causally related is still uncertain. We aimed to investigate the relationship between influenza infection and IPD in Ontario, Canada, using several complementary methodological tools. METHODS AND FINDINGS: We evaluated a total number of 38,501 positive influenza tests in Central Ontario and 6,191 episodes of IPD in the Toronto/Peel area, Ontario, Canada, between 1 January 1995 and 3 October 2009, reported through population-based surveillance. We assessed the relationship between the seasonal wave forms for influenza and IPD using fast Fourier transforms in order to examine the relationship between these two pathogens over yearly timescales. We also used three complementary statistical methods (time-series methods, negative binomial regression, and case-crossover methods) to evaluate the short-term effect of influenza dynamics on pneumococcal risk. Annual periodicity with wintertime peaks could be demonstrated for IPD, whereas periodicity for influenza was less regular. As for long-term effects, phase and amplitude terms of pneumococcal and influenza seasonal sine waves were not correlated and meta-analysis confirmed significant heterogeneity of influenza, but not pneumococcal phase terms. In contrast, influenza was shown to Granger-cause pneumococcal disease. A short-term association between IPD and influenza could be demonstrated for 1-week lags in both case-crossover (odds ratio [95% confidence interval] for one case of IPD per 100 influenza cases = 1.10 [1.02–1.18]) and negative binomial regression analysis (incidence rate ratio [95% confidence interval] for one case of IPD per 100 influenza cases = 1.09 [1.05–1.14]). CONCLUSIONS: Our data support the hypothesis that influenza influences bacterial disease incidence by enhancing short-term risk of invasion in colonized individuals. The absence of correlation between seasonal waveforms, on the other hand, suggests that bacterial disease transmission is affected to a lesser extent. Please see later in the article for the Editors' Summary",2011 Jun 7,"['Kuster, Stefan P.', 'Tuite, Ashleigh R.', 'Kwong, Jeffrey C.', 'McGeer, Allison', None, 'Fisman, David N.']",PLoS Med,,,True
6bf7eb57bcb46ac71e49305ef93f2acafc869e9b,PMC,The Pathogenesis of Rift Valley Fever,http://dx.doi.org/10.3390/v3050493,PMC3111045,21666766,CC BY,"Rift Valley fever (RVF) is an emerging zoonotic disease distributed in sub-Saharan African countries and the Arabian Peninsula. The disease is caused by the Rift Valley fever virus (RVFV) of the family Bunyaviridae and the genus Phlebovirus. The virus is transmitted by mosquitoes, and virus replication in domestic ruminant results in high rates of mortality and abortion. RVFV infection in humans usually causes a self-limiting, acute and febrile illness; however, a small number of cases progress to neurological disorders, partial or complete blindness, hemorrhagic fever, or thrombosis. This review describes the pathology of RVF in human patients and several animal models, and summarizes the role of viral virulence factors and host factors that affect RVFV pathogenesis.",2011 May 6,"['Ikegami, Tetsuro', 'Makino, Shinji']",Viruses,,,True
ebe8d3845bdfbc11f865667d68399c4862551d30,PMC,Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence,http://dx.doi.org/10.1371/journal.ppat.1002090,PMC3111541,21695242,CC BY,"Transmissible gastroenteritis virus (TGEV) genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7). Both the mutant and the parental (rTGEV-wt) viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α) phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c), a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the acquisition of gene 7 by the TGEV genome most likely has provided a selective advantage to the virus.",2011 Jun 9,"['Cruz, Jazmina L. G.', 'Sola, Isabel', 'Becares, Martina', 'Alberca, Berta', 'Plana, Joan', 'Enjuanes, Luis', 'Zuñiga, Sonia']",PLoS Pathog,,,True
fe954b75ed45c02d47090ee70d25c726b24b081c,PMC,"Knowledge, Attitudes and Practices (KAP) related to the Pandemic (H1N1) 2009 among Chinese General Population: a Telephone Survey",http://dx.doi.org/10.1186/1471-2334-11-128,PMC3112099,21575222,CC BY,"BACKGROUND: China is at greatest risk of the Pandemic (H1N1) 2009 due to its huge population and high residential density. The unclear comprehension and negative attitudes towards the emerging infectious disease among general population may lead to unnecessary worry and even panic. The objective of this study was to investigate the Chinese public response to H1N1 pandemic and provide baseline data to develop public education campaigns in response to future outbreaks. METHODS: A close-ended questionnaire developed by the Chinese Center for Disease Control and Prevention was applied to assess the knowledge, attitudes and practices (KAP) of pandemic (H1N1) 2009 among 10,669 responders recruited from seven urban and two rural areas of China sampled by using the probability proportional to size (PPS) method. RESULTS: 30.0% respondents were not clear whether food spread H1N1 virusand. 65.7% reported that the pandemic had no impact on their life. The immunization rates of the seasonal flu and H1N1vaccine were 7.5% and 10.8%, respectively. Farmers and those with lower education level were less likely to know the main transmission route (cough or talk face to face). Female and those with college and above education had higher perception of risk and more compliance with preventive behaviors. Relationships between knowledge and risk perception (OR = 1.69; 95%CI 1.54-1.86), and knowledge and practices (OR = 1.57; 95%CI 1.42-1.73) were found among the study subjects. With regard to the behavior of taking up A/H1N1 vaccination, there are several related factors found in the current study population, including the perception of life disturbed (OR = 1.29; 95%CI 1.11-1.50), the safety of A/H1N1 vaccine (OR = 0.07; 95%CI 0.04-0.11), the knowledge of free vaccination policy (OR = 7.20; 95%CI 5.91-8.78), the state's priority vaccination strategy(OR = 1.33; 95%CI 1.08-1.64), and taking up seasonal influenza vaccine behavior (OR = 4.69; 95%CI 3.53-6.23). CONCLUSIONS: This A/H1N1 epidemic has not caused public panic yet, but the knowledge of A/H1N1 in residents is not optimistic. Public education campaign may take the side effects of vaccine and the knowledge about the state's vaccination strategy into account.",2011 May 16,"['Lin, Yilan', 'Huang, Lijuan', 'Nie, Shaofa', 'Liu, Zengyan', 'Yu, Hongjie', 'Yan, Weirong', 'Xu, Yihua']",BMC Infect Dis,,,True
e9b2d0e930a4e8ec960b5e4dc7e627b4d243ac0f,PMC,"Novel viral vectors utilizing intron splice-switching to activate genome rescue, expression and replication in targeted cells",http://dx.doi.org/10.1186/1743-422X-8-243,PMC3113310,21595942,CC BY,"BACKGROUND: The outcome of virus infection depends from the precise coordination of viral gene expression and genome replication. The ability to control and regulate these processes is therefore important for analysis of infection process. Viruses are also useful tools in bio- and gene technology; they can efficiently kill cancer cells and trigger immune responses to tumors. However, the methods for constructing tissue- or cell-type specific viruses typically suffer from low target-cell specificity and a high risk of reversion. Therefore novel and universal methods of regulation of viral infection are also important for therapeutic application of virus-based systems. METHODS: Aberrantly spliced introns were introduced into crucial gene-expression units of adenovirus vector and alphavirus DNA/RNA layered vectors and their effects on the viral gene expression, replication and/or the release of infectious genomes were studied in cell culture. Transfection of the cells with splice-switching oligonucleotides was used to correct the introduced functional defect(s). RESULTS: It was demonstrated that viral gene expression, replication and/or the release of infectious genomes can be blocked by the introduction of aberrantly spliced introns. The insertion of such an intron into an adenovirus vector reduced the expression of the targeted gene more than fifty-fold. A similar insertion into an alphavirus DNA/RNA layered vector had a less dramatic effect; here, only the release of the infectious transcript was suppressed but not the subsequent replication and spread of the virus. However the insertion of two aberrantly spliced introns resulted in an over one hundred-fold reduction in the infectivity of the DNA/RNA layered vector. Furthermore, in both systems the observed effects could be reverted by the delivery of splice-switching oligonucleotide(s), which corrected the splicing defects. CONCLUSIONS: Splice-switch technology, originally developed for genetic disease therapy, can also be used to control gene expression of viral vectors. This approach represents a novel, universal and powerful method for controlling gene expression, replication, viral spread and, by extension, virus-induced cytotoxic effects and can be used both for basic studies of virus infection and in virus-based gene- and anti-cancer therapy.",2011 May 19,"['Viru, Liane', 'Heller, Gregory', 'Lehto, Taavi', 'Pärn, Kalle', 'El Andaloussi, Samir', 'Langel, Ülo', 'Merits, Andres']",Virol J,,,True
4481ddf0d81e186b0be8ab48c20e8b206ec2879c,PMC,Non-Apical Membrane Antigen 1 (AMA1) IgGs from Malian Children Interfere with Functional Activity of AMA1 IgGs as Judged by Growth Inhibition Assay,http://dx.doi.org/10.1371/journal.pone.0020947,PMC3113848,21695140,CC0,"BACKGROUND: Apical membrane antigen 1 (AMA1) is one of the best-studied blood-stage malaria vaccine candidates. When an AMA1 vaccine was tested in a malaria naïve population, it induced functionally active antibodies judged by Growth Inhibition Assay (GIA). However, the same vaccine failed to induce higher growth-inhibitory activity in adults living in a malaria endemic area. Vaccination did induce functionally active antibodies in malaria-exposed children with less than 20% inhibition in GIA at baseline, but not in children with more than that level of baseline inhibition. METHODS: Total IgGs were purified from plasmas collected from the pediatric trial before and after immunization and pools of total IgGs were made. Another set of total IgGs was purified from U.S. adults immunized with AMA1 (US-total IgG). From these total IgGs, AMA1-specific and non-AMA1 IgGs were affinity purified and the functional activity of these IgGs was evaluated by GIA. Competition ELISA was performed with the U.S.-total IgG and non-AMA1 IgGs from malaria-exposed children. RESULTS: AMA1-specific IgGs from malaria-exposed children and U.S. vaccinees showed similar growth-inhibitory activity at the same concentrations. When mixed with U.S.-total IgG, non-AMA1 IgGs from children showed an interference effect in GIA. Interestingly, the interference effect was higher with non-AMA1 IgGs from higher titer pools. The non-AMA1 IgGs did not compete with anti-AMA1 antibody in U.S.-total IgG in the competition ELISA. CONCLUSION: Children living in a malaria endemic area have a fraction of IgGs that interferes with the biological activity of anti-AMA1 antibody as judged by GIA. While the mechanism of interference is not resolved in this study, these results suggest it is not caused by direct competition between non-AMA1 IgG and AMA1 protein. This study indicates that anti-malaria IgGs induced by natural exposure may interfere with the biological effect of antibody induced by an AMA1-based vaccine in the target population.",2011 Jun 13,"['Miura, Kazutoyo', 'Perera, Suwani', 'Brockley, Sarah', 'Zhou, Hong', 'Aebig, Joan A.', 'Moretz, Samuel E.', 'Miller, Louis H.', 'Doumbo, Ogobara K.', 'Sagara, Issaka', 'Dicko, Alassane', 'Ellis, Ruth D.', 'Long, Carole A.']",PLoS One,,,True
2d32032f8498219617634b8b4e5f5c7d214d2ebb,PMC,The usefulness of case reports in managing emerging infectious disease,http://dx.doi.org/10.1186/1752-1947-5-194,PMC3113999,21599907,CC BY,"Emerging infectious diseases are an important problem in medicine. Case reports usually document episodes in the early emerging phase or in a small outbreak. Although the case report is considered weak evidence in medical literature, it is usually the first report when there is a new emerging infectious disease. There is no doubt that case reports can provide useful information for further case series, reviews and studies. This editorial focuses on the usefulness of the case report on emerging infectious disease to the medical society. Publication in this area is highly welcomed by the journal and can serve as a future point of reference.",2011 May 20,"Wiwanitkit, Viroj",J Med Case Reports,,,True
8866d2274d3ecb0ef50ccf806d9e03839ad2edbc,PMC,PCR Improves Diagnostic Yield from Lung Aspiration in Malawian Children with Radiologically Confirmed Pneumonia,http://dx.doi.org/10.1371/journal.pone.0021042,PMC3114850,21695128,CC BY,"BACKGROUND: Accurate data on childhood pneumonia aetiology are essential especially from regions where mortality is high, in order to inform case-management guidelines and the potential of prevention strategies such as bacterial conjugate vaccines. Yield from blood culture is low, but lung aspirate culture provides a higher diagnostic yield. We aimed to determine if diagnostic yield could be increased further by polymerase chain reaction (PCR) detection of bacteria (Streptococcus pneumoniae and Haemophilus influenzae b) and viruses in lung aspirate fluid. METHODS: A total of 95 children with radiological focal, lobar or segmental consolidation had lung aspirate performed and sent for bacterial culture and for PCR for detection of bacteria, viruses and Pneumocystis jirovecii. In children with a pneumococcal aetiology, pneumococcal bacterial loads were calculated in blood and lung aspirate fluid. RESULTS: Blood culture identified a bacterial pathogen in only 8 patients (8%). With the addition of PCR on lung aspirate samples, causative pathogens (bacterial, viral, pneumocystis) were identified singly or as co-infections in 59 children (62%). The commonest bacterial organism was S.pneumoniae (41%), followed by H. influenzae b (6%), and the commonest virus identified was adenovirus (16%), followed by human bocavirus (HBoV) (4%), either as single or co-infection. CONCLUSIONS: In a select group of African children, lung aspirate PCR significantly improves diagnostic yield. Our study confirms a major role of S.pneumoniae and viruses in the aetiology of childhood pneumonia in Africa.",2011 Jun 14,"['Carrol, Enitan D.', 'Mankhambo, Limangeni A.', 'Guiver, Malcolm', 'Banda, Daniel L.', None, 'Denis, Brigitte', 'Dove, Winifred', 'Jeffers, Graham', 'Molyneux, Elizabeth M.', 'Molyneux, Malcolm E.', 'Hart, C. Anthony', 'Graham, Stephen M.']",PLoS One,,,True
93b3fcce1e0a7c9a82091bd832b1b3a286133679,PMC,Influenza A Virus Nucleoprotein Exploits Hsp40 to Inhibit PKR Activation,http://dx.doi.org/10.1371/journal.pone.0020215,PMC3115951,21698289,CC0,"BACKGROUND: Double-stranded RNA dependent protein kinase (PKR) is a key regulator of the anti-viral innate immune response in mammalian cells. PKR activity is regulated by a 58 kilo Dalton cellular inhibitor (P58(IPK)), which is present in inactive state as a complex with Hsp40 under normal conditions. In case of influenza A virus (IAV) infection, P58(IPK) is known to dissociate from Hsp40 and inhibit PKR activation. However the influenza virus component responsible for PKR inhibition through P58(IPK) activation was hitherto unknown. PRINCIPAL FINDINGS: Human heat shock 40 protein (Hsp40) was identified as an interacting partner of Influenza A virus nucleoprotein (IAV NP) using a yeast two-hybrid screen. This interaction was confirmed by co-immunoprecipitation studies from mammalian cells transfected with IAV NP expressing plasmid. Further, the IAV NP-Hsp40 interaction was validated in mammalian cells infected with various seasonal and pandemic strains of influenza viruses. Cellular localization studies showed that NP and Hsp40 co-localize primarily in the nucleus. During IAV infection in mammalian cells, expression of NP coincided with the dissociation of P58(IPK) from Hsp40 and decrease PKR phosphorylation. We observed that, plasmid based expression of NP in mammalian cells leads to decrease in PKR phosphorylation. Furthermore, inhibition of NP expression during influenza virus replication led to PKR activation and concomitant increase in eIF2α phosphorylation. Inhibition of NP expression also led to reduced IRF3 phosphorylation, enhanced IFN β production and concomitant reduction of virus replication. Taken together our data suggest that NP is the viral factor responsible for P58(IPK) activation and subsequent inhibition of PKR-mediated host response during IAV infection. SIGNIFICANCE: Our findings demonstrate a novel role of IAV NP in inhibiting PKR-mediated anti-viral host response and help us understand P58(IPK) mediated inhibition of PKR activity during IAV infection.",2011 Jun 15,"['Sharma, Kulbhushan', 'Tripathi, Shashank', 'Ranjan, Priya', 'Kumar, Purnima', 'Garten, Rebecca', 'Deyde, Varough', 'Katz, Jacqueline M.', 'Cox, Nancy J.', 'Lal, Renu B.', 'Sambhara, Suryaprakash', 'Lal, Sunil K.']",PLoS One,,,True
69ddca48a5d1e593fbd057160b100afb374276c8,PMC,Equine Torovirus (BEV) Induces Caspase-Mediated Apoptosis in Infected Cells,http://dx.doi.org/10.1371/journal.pone.0020972,PMC3115971,21698249,CC BY,"Toroviruses are gastroenteritis causing agents that infect different animal species and humans. To date, very little is known about how toroviruses cause disease. Here, we describe for the first time that the prototype member of this genus, the equine torovirus Berne virus (BEV), induces apoptosis in infected cells at late times postinfection. Observation of BEV infected cells by electron microscopy revealed that by 24 hours postinfection some cells exhibited morphological characteristics of apoptotic cells. Based on this finding, we analyzed several apoptotic markers, and observed protein synthesis inhibition, rRNA and DNA degradation, nuclear fragmentation, caspase-mediated cleavage of PARP and eIF4GI, and PKR and eIF2α phosphorylation, all these processes taking place after peak virus production. We also determined that both cell death receptor and mitochondrial pathways are involved in the apoptosis process induced by BEV. BEV-induced apoptosis at late times postinfection, once viral progeny are produced, could facilitate viral dissemination in vivo and contribute to viral pathogenesis.",2011 Jun 15,"['Maestre, Ana M.', 'Garzón, Ana', 'Rodríguez, Dolores']",PLoS One,,,True
621648da481a06d1a2bb80c56e998f7373215be6,PMC,Hepatitis B Virus Genotype G forms core-like particles with unique structural properties,http://dx.doi.org/10.1111/j.1365-2893.2010.01330.x,PMC3116152,20546498,CC BY,"SUMMARY: We have determined the structure of the core capsid of an unusual variant of hepatitis B virus, genotype G (HBV/G) at 14 Å resolution, using cryo-electron microscopy. The structure reveals surface features not present in the prototype HBV/A genotype. HBV/G is novel in that it has a unique 36- bp insertion downstream of the core gene start codon. This results in a twelve amino acid insertion at the N-terminal end of the core protein, and two stop codons in the precore region that prevent the expression of HBeAg. HBV/G replication in patients is associated with co-infection with another genotype of HBV, suggesting that HBV/G may have reduced replication efficiency in vivo. We localized the N-terminal insertion in HBV/G and show that it forms two additional masses on the core surface adjacent to each of the dimer-spikes and have modelled the structure of the additional residues within this density. We show that the position of the insertion would not interfere with translocation of nucleic acids through the pores to the core interior compartment. However, the insertion may partially obscure several residues on the core surface that are known to play a role in envelopment and secretion of virions, or that could affect structural rearrangements that may trigger envelopment after DNA second-strand synthesis.",2011 Jun,"['Cotelesage, J J H', 'Osiowy, C', 'Lawrence, C', 'deVarennes, S L', 'Teow, S', 'Beniac, D R', 'Booth, T F']",J Viral Hepat,,,True
bb01f3bd0a1b61ef92b556330b94f59c947ea1a9,PMC,A Functional Role for ADAM10 in Human Immunodeficiency Virus Type-1 Replication,http://dx.doi.org/10.1186/1742-4690-8-32,PMC3118345,21569301,CC BY,"BACKGROUND: Gene trap insertional mutagenesis was used as a high-throughput approach to discover cellular genes participating in viral infection by screening libraries of cells selected for survival from lytic infection with a variety of viruses. Cells harboring a disrupted ADAM10 (A Disintegrin and Metalloprotease 10) allele survived reovirus infection, and subsequently ADAM10 was shown by RNA interference to be important for replication of HIV-1. RESULTS: Silencing ADAM10 expression with small interfering RNA (siRNA) 48 hours before infection significantly inhibited HIV-1 replication in primary human monocyte-derived macrophages and in CD4(+ )cell lines. In agreement, ADAM10 over-expression significantly increased HIV-1 replication. ADAM10 down-regulation did not inhibit viral reverse transcription, indicating that viral entry and uncoating are also independent of ADAM10 expression. Integration of HIV-1 cDNA was reduced in ADAM10 down-regulated cells; however, concomitant 2-LTR circle formation was not detected, suggesting that HIV-1 does not enter the nucleus. Further, ADAM10 silencing inhibited downstream reporter gene expression and viral protein translation. Interestingly, we found that while the metalloprotease domain of ADAM10 is not required for HIV-1 replication, ADAM15 and γ-secretase (which proteolytically release the extracellular and intracellular domains of ADAM10 from the plasma membrane, respectively) do support productive infection. CONCLUSIONS: We propose that ADAM10 facilitates replication at the level of nuclear trafficking. Collectively, our data support a model whereby ADAM10 is cleaved by ADAM15 and γ-secretase and that the ADAM10 intracellular domain directly facilitates HIV-1 nuclear trafficking. Thus, ADAM10 represents a novel cellular target class for development of antiretroviral drugs.",2011 May 11,"['Friedrich, Brian M', 'Murray, James L', 'Li, Guangyu', 'Sheng, Jinsong', 'Hodge, Thomas W', 'Rubin, Donald H', ""O'Brien, William A"", 'Ferguson, Monique R']",Retrovirology,,,True
6c5521b73b11d4e229b4ca98f116bc32aa4052c3,PMC,Probing genomic diversity and evolution of Streptococcus suis serotype 2 by NimbleGen tiling arrays,http://dx.doi.org/10.1186/1471-2164-12-219,PMC3118785,21554741,CC BY,"BACKGROUND: Our previous studies revealed that a new disease form of streptococcal toxic shock syndrome (STSS) is associated with specific Streptococcus suis serotype 2 (SS2) strains. To achieve a better understanding of the pathogenicity and evolution of SS2 at the whole-genome level, comparative genomic analysis of 18 SS2 strains, selected on the basis of virulence and geographic origin, was performed using NimbleGen tiling arrays. RESULTS: Our results demonstrate that SS2 isolates have highly divergent genomes. The 89K pathogenicity island (PAI), which has been previously recognized as unique to the Chinese epidemic strains causing STSS, was partially included in some other virulent and avirulent strains. The ABC-type transport systems, encoded by 89K, were hypothesized to greatly contribute to the catastrophic features of STSS. Moreover, we identified many polymorphisms in genes encoding candidate or known virulence factors, such as PlcR, lipase, sortases, the pilus-associated proteins, and the response regulator RevS and CtsR. On the basis of analysis of regions of differences (RDs) across the entire genome for the 18 selected SS2 strains, a model of microevolution for these strains is proposed, which provides clues into Streptococcus pathogenicity and evolution. CONCLUSIONS: Our deep comparative genomic analysis of the 89K PAI present in the genome of SS2 strains revealed details into how some virulent strains acquired genes that may contribute to STSS, which may lead to better environmental monitoring of epidemic SS2 strains.",2011 May 10,"['Wu, Zuowei', 'Li, Ming', 'Wang, Changjun', 'Li, Jing', 'Lu, Na', 'Zhang, Ruifen', 'Jiang, Yongqiang', 'Yang, Ruifu', 'Liu, Cuihua', 'Liao, Hui', 'Gao, George F', 'Tang, Jiaqi', 'Zhu, Baoli']",BMC Genomics,,,True
cb76568fb12e6a9802c85a994def23156d29352b,PMC,Remote Data Retrieval for Bioinformatics Applications: An Agent Migration Approach,http://dx.doi.org/10.1371/journal.pone.0020949,PMC3119054,21701677,CC BY,"Some of the approaches have been developed to retrieve data automatically from one or multiple remote biological data sources. However, most of them require researchers to remain online and wait for returned results. The latter not only requires highly available network connection, but also may cause the network overload. Moreover, so far none of the existing approaches has been designed to address the following problems when retrieving the remote data in a mobile network environment: (1) the resources of mobile devices are limited; (2) network connection is relatively of low quality; and (3) mobile users are not always online. To address the aforementioned problems, we integrate an agent migration approach with a multi-agent system to overcome the high latency or limited bandwidth problem by moving their computations to the required resources or services. More importantly, the approach is fit for the mobile computing environments. Presented in this paper are also the system architecture, the migration strategy, as well as the security authentication of agent migration. As a demonstration, the remote data retrieval from GenBank was used to illustrate the feasibility of the proposed approach.",2011 Jun 20,"['Gao, Lei', 'Dai, Hua', 'Zhang, Tong-Liang', 'Chou, Kuo-Chen']",PLoS One,,,True
01e22956c79df3220a67bce71cf22de95d29b723,PMC,In-Depth Analysis of the Antibody Response of Individuals Exposed to Primary Dengue Virus Infection,http://dx.doi.org/10.1371/journal.pntd.0001188,PMC3119640,21713020,CC BY,"Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization.",2011 Jun 21,"['de Alwis, Ruklanthi', 'Beltramello, Martina', 'Messer, William B.', 'Sukupolvi-Petty, Soila', 'Wahala, Wahala M. P. B.', 'Kraus, Annette', 'Olivarez, Nicholas P.', 'Pham, Quang', 'Brian, James', 'Tsai, Wen-Yang', 'Wang, Wei-Kung', 'Halstead, Scott', 'Kliks, Srisakul', 'Diamond, Michael S.', 'Baric, Ralph', 'Lanzavecchia, Antonio', 'Sallusto, Federica', 'de Silva, Aravinda M.']",PLoS Negl Trop Dis,,,True
51b2c04a95156d66aec99817f2dc769566cace9d,PMC,Spatial and Temporal Characteristics of the 2009 A/H1N1 Influenza Pandemic in Peru,http://dx.doi.org/10.1371/journal.pone.0021287,PMC3119673,21712984,CC0,"BACKGROUND: Highly refined surveillance data on the 2009 A/H1N1 influenza pandemic are crucial to quantify the spatial and temporal characteristics of the pandemic. There is little information about the spatial-temporal dynamics of pandemic influenza in South America. Here we provide a quantitative description of the age-specific morbidity pandemic patterns across administrative areas of Peru. METHODS: We used daily cases of influenza-like-illness, tests for A/H1N1 influenza virus infections, and laboratory-confirmed A/H1N1 influenza cases reported to the epidemiological surveillance system of Peru's Ministry of Health from May 1 to December 31, 2009. We analyzed the geographic spread of the pandemic waves and their association with the winter school vacation period, demographic factors, and absolute humidity. We also estimated the reproduction number and quantified the association between the winter school vacation period and the age distribution of cases. RESULTS: The national pandemic curve revealed a bimodal winter pandemic wave, with the first peak limited to school age children in the Lima metropolitan area, and the second peak more geographically widespread. The reproduction number was estimated at 1.6–2.2 for the Lima metropolitan area and 1.3–1.5 in the rest of Peru. We found a significant association between the timing of the school vacation period and changes in the age distribution of cases, while earlier pandemic onset was correlated with large population size. By contrast there was no association between pandemic dynamics and absolute humidity. CONCLUSIONS: Our results indicate substantial spatial variation in pandemic patterns across Peru, with two pandemic waves of varying timing and impact by age and region. Moreover, the Peru data suggest a hierarchical transmission pattern of pandemic influenza A/H1N1 driven by large population centers. The higher reproduction number of the first pandemic wave could be explained by high contact rates among school-age children, the age group most affected during this early wave.",2011 Jun 21,"['Chowell, Gerardo', 'Viboud, Cécile', 'Munayco, Cesar V.', 'Gómez, Jorge', 'Simonsen, Lone', 'Miller, Mark A.', 'Tamerius, James', 'Fiestas, Victor', 'Halsey, Eric S.', 'Laguna-Torres, Victor A.']",PLoS One,,,True
7835feab0d31096fada1a14d10d67acc080a7d82,PMC,Rhinovirus Genome Variation during Chronic Upper and Lower Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.pone.0021163,PMC3119694,21713005,CC BY,"Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. By contrast, protracted infections were found almost exclusively in immunocompromised patients, thus suggesting that host factors rather than the virus genotype modulate disease outcome, in particular the immune response. Complete genome sequencing of five chronic cases to study rhinovirus genome adaptation showed that the calculated mutation frequency was in the range observed during acute human infections. Analysis of mutation hot spot regions between specimens collected at different times or in different body sites revealed that non-synonymous changes were mostly concentrated in the viral capsid genes VP1, VP2 and VP3, independent of the HRV type. In an immunosuppressed lung transplant recipient infected with the same HRV strain for more than two years, both classical and ultra-deep sequencing of samples collected at different time points in the upper and lower respiratory tracts showed that these virus populations were phylogenetically indistinguishable over the course of infection, except for the last month. Specific signatures were found in the last two lower respiratory tract populations, including changes in the 5′UTR polypyrimidine tract and the VP2 immunogenic site 2. These results highlight for the first time the ability of a given rhinovirus to evolve in the course of a natural infection in immunocompromised patients and complement data obtained from previous experimental inoculation studies in immunocompetent volunteers.",2011 Jun 21,"['Tapparel, Caroline', 'Cordey, Samuel', 'Junier, Thomas', 'Farinelli, Laurent', 'Van Belle, Sandra', 'Soccal, Paola M.', 'Aubert, John-David', 'Zdobnov, Evgeny', 'Kaiser, Laurent']",PLoS One,,,True
de036403a12da2e18921c87a92cf8bcc67e9c051,PMC,Rhinovirus Genome Variation during Chronic Upper and Lower Respiratory Tract Infections,http://dx.doi.org/10.1371/journal.pone.0021163,PMC3119694,21713005,CC BY,"Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. By contrast, protracted infections were found almost exclusively in immunocompromised patients, thus suggesting that host factors rather than the virus genotype modulate disease outcome, in particular the immune response. Complete genome sequencing of five chronic cases to study rhinovirus genome adaptation showed that the calculated mutation frequency was in the range observed during acute human infections. Analysis of mutation hot spot regions between specimens collected at different times or in different body sites revealed that non-synonymous changes were mostly concentrated in the viral capsid genes VP1, VP2 and VP3, independent of the HRV type. In an immunosuppressed lung transplant recipient infected with the same HRV strain for more than two years, both classical and ultra-deep sequencing of samples collected at different time points in the upper and lower respiratory tracts showed that these virus populations were phylogenetically indistinguishable over the course of infection, except for the last month. Specific signatures were found in the last two lower respiratory tract populations, including changes in the 5′UTR polypyrimidine tract and the VP2 immunogenic site 2. These results highlight for the first time the ability of a given rhinovirus to evolve in the course of a natural infection in immunocompromised patients and complement data obtained from previous experimental inoculation studies in immunocompetent volunteers.",2011 Jun 21,"['Tapparel, Caroline', 'Cordey, Samuel', 'Junier, Thomas', 'Farinelli, Laurent', 'Van Belle, Sandra', 'Soccal, Paola M.', 'Aubert, John-David', 'Zdobnov, Evgeny', 'Kaiser, Laurent']",PLoS One,,,False
de793a20bfe9029e76531469de1054c4d5ef37c7,PMC,Immunogenicity and safety of virus-like particle of the porcine encephalomyocarditis virus in pig,http://dx.doi.org/10.1186/1743-422X-8-170,PMC3119933,21492483,CC BY,"BACKGROUND: In this study, porcine encephalomyocarditis virus (EMCV) virus-like particles (VLPs) were generated using a baculovirus expression system and were tested for immunogenicity and protective efficacy in vivo. RESULTS: VLPs were successfully generated from Sf9 cells infected with recombinant baculovirus and were confirmed to be approximately 30-40 nm by transmission electron microscopy (TEM). Immunization of mice with 0.5 μg crude protein containing the VLPs resulted in significant protection from EMCV infection (90%). In swine, increased neutralizing antibody titers were observed following twice immunization with 2.0 μg crude protein containing VLPs. In addition, high levels of neutralizing antibodies (from 64 to 512 fold) were maintained during a test period following the second immunization. No severe injection site reactions were observed after immunization and all swine were healthy during the immunization period CONCLUSION: Recombinant EMCV VLPs could represent a new vaccine candidate to protect against EMCV infection in pig farms.",2011 Apr 15,"['Jeoung, Hye-Young', 'Lee, Won-Ha', 'Jeong, WooSeog', 'Shin, Bo-Hye', 'Choi, Hwan-Won', 'Lee, Hee Soo', 'An, Dong-Jun']",Virol J,,,True
f6fa68c5038374d5ae1b2c1e5a0929e6c1e8ea44,PMC,Overexpression of human virus surface glycoprotein precursors induces cytosolic unfolded protein response in Saccharomyces cerevisiae,http://dx.doi.org/10.1186/1475-2859-10-37,PMC3120639,21595909,CC BY,"BACKGROUND: The expression of human virus surface proteins, as well as other mammalian glycoproteins, is much more efficient in cells of higher eukaryotes rather than yeasts. The limitations to high-level expression of active viral surface glycoproteins in yeast are not well understood. To identify possible bottlenecks we performed a detailed study on overexpression of recombinant mumps hemagglutinin-neuraminidase (MuHN) and measles hemagglutinin (MeH) in yeast Saccharomyces cerevisiae, combining the analysis of recombinant proteins with a proteomic approach. RESULTS: Overexpressed recombinant MuHN and MeH proteins were present in large aggregates, were inactive and totally insoluble under native conditions. Moreover, the majority of recombinant protein was found in immature form of non-glycosylated precursors. Fractionation of yeast lysates revealed that the core of viral surface protein aggregates consists of MuHN or MeH disulfide-linked multimers involving eukaryotic translation elongation factor 1A (eEF1A) and is closely associated with small heat shock proteins (sHsps) that can be removed only under denaturing conditions. Complexes of large Hsps seem to be bound to aggregate core peripherally as they can be easily removed at high salt concentrations. Proteomic analysis revealed that the accumulation of unglycosylated viral protein precursors results in specific cytosolic unfolded protein response (UPR-Cyto) in yeast cells, characterized by different action and regulation of small Hsps versus large chaperones of Hsp70, Hsp90 and Hsp110 families. In contrast to most environmental stresses, in the response to synthesis of recombinant MuHN and MeH, only the large Hsps were upregulated whereas sHsps were not. Interestingly, the amount of eEF1A was also increased during this stress response. CONCLUSIONS: Inefficient translocation of MuHN and MeH precursors through ER membrane is a bottleneck for high-level expression in yeast. Overexpression of these recombinant proteins induces the UPR's cytosolic counterpart, the UPR-Cyto, which represent a subset of proteins involved in the heat-shock response. The involvement of eEF1A may explain the mechanism by which only large chaperones, but not small Hsps are upregulated during this stress response. Our study highlights important differences between viral surface protein expression in yeast and mammalian cells at the first stage of secretory pathway.",2011 May 19,"['Čiplys, Evaldas', 'Samuel, Dhanraj', 'Juozapaitis, Mindaugas', 'Sasnauskas, Kęstutis', 'Slibinskas, Rimantas']",Microb Cell Fact,,,True
63cb88b9fee3f16bcf3666b4665e445325addf9d,PMC,Lytic HSV-1 infection induces the multifunctional transcription factor Early Growth Response-1 (EGR-1) in rabbit corneal cells,http://dx.doi.org/10.1186/1743-422X-8-262,PMC3120787,21619646,CC BY,"BACKGROUND: Herpes simplex virus type-1 (HSV-1) infections can cause a number of diseases ranging from simple cold sores to dangerous keratitis and lethal encephalitis. The interaction between virus and host cells, critical for viral replication, is being extensively investigated by many laboratories. In this study, we tested the hypothesis that HSV-1 lytic infection triggers the expression of important multi-functional transcription factor Egr1. The mechanisms of induction are mediated, at least in part, by signaling pathways such as NFκB and CREB. METHODS: SIRC, VERO, and 293HEK cell lines were infected with HSV-1, and the Egr-1 transcript and protein were detected by RT-PCR and Western blot, respectively. The localization and expression profile of Egr-1 were investigated further by immunofluorescence microscopy analyses. The recruitment of transcription factors to the Egr-1 promoter during infection was studied by chromatin immunoprecipitation (ChIP). Various inhibitors and dominant-negative mutant were used to assess the mechanisms of Egr-1 induction and their effects were addressed by immunofluorescence microscopy. RESULTS: Western blot analyses showed that Egr-1 was absent in uninfected cells; however, the protein was detected 24-72 hours post treatment, and the response was directly proportional to the titer of the virus used for infection. Using recombinant HSV-1 expressing EGFP, Egr-1 was detected only in the infected cells. ChIP assays demonstrated that NFкB and cAMP response element binding protein (CREB) were recruited to the Egr-1 promoter upon infection. Additional studies showed that inhibitors of NFкB and dominant-negative CREB repressed the Egr-1 induction by HSV-1 infection. CONCLUSION: Collectively, these results demonstrate that Egr-1 is expressed rapidly upon HSV-1 infection and that this novel induction could be due to the NFкB/CREB-mediated transactivation. Egr-1 induction might play a key role in the viral gene expression, replication, inflammation, and the disease progression.",2011 May 27,"['Bedadala, Gautam R', 'Palem, Jayavardhana R', 'Graham, Lorna', 'Hill, James M', 'McFerrin, Harris E', 'Hsia, Shao-Chung']",Virol J,,,True
052a16d442ede77ed4bdeaa05037270f251dedc4,PMC,A baculovirus dual expression system-based vaccine confers complete protection against lethal challenge with H9N2 avian influenza virus in mice,http://dx.doi.org/10.1186/1743-422X-8-273,PMC3120790,21639929,CC BY,"BACKGROUND: Avian influenza viruses of H9N2 subtype have become highly prevalent in avian species. Although these viruses generally cause only mild to moderate disease, they can infect a wide variety of species, including chickens, quail, turkeys, ducks, geese, pheasant, partridge, and pigeon, even transmitted to mammalian species, including humans, accelerating the efforts to devise protective strategies against them. RESULTS: The results showed that stronger immune responses were induced in a mouse model immunized with BV-Dual-HA than in those vaccinated with a DNA vaccine encoding the same antigen. Moreover, complete protection against lethal challenge with H9N2 virus was observed in mice. CONCLUSION: BV-Dual-HA could be utilized as a vaccine candidate against H9N2 virus infection.",2011 Jun 4,"['Lin, Wenyao', 'Fan, Huiying', 'Cheng, Xiaoliang', 'Ye, Yu', 'Chen, Xiaowei', 'Ren, Tao', 'Qi, Wenbao', 'Liao, Ming']",Virol J,,,True
db7db8941a68a14e0b227ce42898ad4ecd40df62,PMC,Public Health Emergency Preparedness and Response Communications with Health Care Providers: A Literature Review,http://dx.doi.org/10.1186/1471-2458-11-337,PMC3121631,21592390,CC BY,"BACKGROUND: Health care providers (HCPs) play an important role in public health emergency preparedness and response (PHEPR) so need to be aware of public health threats and emergencies. To inform HCPs, public health issues PHEPR messages that provide guidelines and updates, and facilitate surveillance so HCPs will recognize and control communicable diseases, prevent excess deaths and mitigate suffering. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. We conducted a literature review to investigate the systems and tools used by public health to generate PHEPR communications to HCPs, and to identify specific characteristics of message delivery mechanisms and formats that may be associated with effective PHEPR communications. METHODS: A systematic review of peer- and non-peer-reviewed literature focused on the following questions: 1) What public health systems exist for communicating PHEPR messages from public health agencies to HCPs? 2) Have these systems been evaluated and, if yes, what criteria were used to evaluate these systems? 3) What have these evaluations discovered about characterizations of the most effective ways for public health agencies to communicate PHEPR messages to HCPs? RESULTS: We identified 25 systems or tools for communicating PHEPR messages from public health agencies to HCPs. Few articles assessed PHEPR communication systems or messaging methods or outcomes. Only one study compared the effectiveness of the delivery format, device or message itself. We also discovered that the potential is high for HCPs to experience ""message overload"" given redundancy of PHEPR messaging in multiple formats and/or through different delivery systems. CONCLUSIONS: We found that detailed descriptions of PHEPR messaging from public health to HCPs are scarce in the literature and, even when available are rarely evaluated in any systematic fashion. To meet present-day and future information needs for emergency preparedness, more attention needs to be given to evaluating the effectiveness of these systems in a scientifically rigorous manner.",2011 May 18,"['Revere, Debra', 'Nelson, Kailey', 'Thiede, Hanne', 'Duchin, Jeffrey', 'Stergachis, Andy', 'Baseman, Janet']",BMC Public Health,,,True
816359485f5bb752e2024fae9fe790cc1ff80f81,PMC,StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase,http://dx.doi.org/10.1186/1471-2105-12-226,PMC3121648,21635786,CC BY,"BACKGROUND: Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory--still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could help overcome these difficulties by facilitating the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. RESULTS: Here we present StralSV (structure-alignment sequence variability), a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus, and we demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique, or that share structural similarity with proteins that would be considered distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local structural alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. CONCLUSIONS: StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected residues at a given sequence position. StralSV is provided as a web service at http://proteinmodel.org/AS2TS/STRALSV/.",2011 Jun 2,"['Zemla, Adam T', 'Lang, Dorothy M', 'Kostova, Tanya', 'Andino, Raul', 'Ecale Zhou, Carol L']",BMC Bioinformatics,,,True
5ffaf1c1d5f763636ec3334c1b1547d4a8b8abb9,PMC,Human bocavirus (HBoV) in children with respiratory tract infection by enzyme linked immunosorbent assay (ELISA) and qualitative polymerase chain reaction (PCR),http://dx.doi.org/10.1186/1743-422X-8-239,PMC3121704,21595869,CC BY,"BACKGROUND: Human bocavirus (HBoV) is a recently discovered parvovirus associated with mild to severe lower respiratory tract infections in children, the aim of the work was determination of human bocavirus in nasopharyngeal aspirate (NPA) of infants by qualitative PCR and determination of acute human bocavirus infection by estimation of immunoglobulin M (IgM) antibodies in serum by enzyme linked immunosorbent assay. RESULTS: Twenty two (22%) out of the 100 NPA specimens of the patients with respiratory manifestations were positive for HBoV by qualitative PCR, while ELISA revealed positive HBoV IgM antibodies in 18 (18%) patients who were also positive by PCR. Non of the controls were positive by both techniques. The correlation study between ELISA and PCR revealed high significant association, (p < 0.001, X(2 )= 36 and agreement = 96%). Also PCR detected 4 (18.1%) NPA samples as HBoV positive cases among the patients that were not identified by ELISA. This could be due to high sensitivity and efficacy of PCR. ELISA being less sensitive than RT-PCR, sensitivity was (81.8% vs 100%), the efficacy was 97.7% in ELISA versus 99.7% for RT-PCR. CONCLUSION: HBoV infections could be diagnosed in NPA of children by conventional PCR as a rapid and sensitive technique. While ELISA was a reliable serologic analysis for diagnosis of acute HBoV infection by estimation IgM antibodies in serum.",2011 May 19,"Zaghloul, Mona Z",Virol J,,,True
a2c46da8970ae5d4e6b3b1f4d4d30a2ea426d1ff,PMC,Self-Collected Mid-Turbinate Swabs for the Detection of Respiratory Viruses in Adults with Acute Respiratory Illnesses,http://dx.doi.org/10.1371/journal.pone.0021335,PMC3121745,21731708,CC BY,"BACKGROUND: The gold standard for respiratory virus testing is a nasopharyngeal (NP) swab, which is collected by a healthcare worker. Midturbinate (MT) swabs are an alternative due to their ease of collection and possible self-collection by patients. The objective of this study was to compare the respiratory virus isolation of flocked MT swabs compared to flocked NP swabs. METHODS: Beginning in October 2008, healthy adults aged 18 to 69 years were recruited into a cohort and followed up for symptoms of influenza. They were asked to have NP and MT swabs taken as soon as possible after the onset of a fever or two or more respiratory symptoms with an acute onset. The swabs were tested for viral respiratory infections using Seeplex® RV12 multiplex PCR detection kit. Seventy six pairs of simultaneous NP and MT swabs were collected from 38 symptomatic subjects. Twenty nine (38%) of these pairs were positive by either NP or MT swabs or both. Sixty nine (91%) of the pair results were concordant. Two samples (3%) for hCV OC43/HKU1 and 1 sample (1%) for rhinovirus A/B were positive by NP but negative by MT. One sample each for hCV 229E/NL63, hCV OC43/HKU1, respiratory syncytial virus A, and influenza B were positive by MT but negative by NP. CONCLUSIONS: Flocked MT swabs are sensitive for the diagnosis of multiple respiratory viruses. Given the ease of MT collection and similar results between the two swabs, it is likely that MT swabs should be the preferred method of respiratory cell collection for outpatient studies. In light of this data, larger studies should be performed to ensure that this still holds true and data should also be collected on the patient preference of collection methods.",2011 Jun 23,"['Larios, Oscar E.', 'Coleman, Brenda L.', 'Drews, Steven J.', 'Mazzulli, Tony', 'Borgundvaag, Bjug', 'Green, Karen', None, 'McGeer, Allison J.']",PLoS One,,,True
d94872b6508c7d1b3bf580ff888aa862047ded07,PMC,Rabies-Related Knowledge and Practices Among Persons At Risk of Bat Exposures in Thailand,http://dx.doi.org/10.1371/journal.pntd.0001054,PMC3125144,21738801,CC0,"BACKGROUND: Rabies is a fatal encephalitis caused by lyssaviruses. Evidence of lyssavirus circulation has recently emerged in Southeast Asian bats. A cross-sectional study was conducted in Thailand to assess rabies-related knowledge and practices among persons regularly exposed to bats and bat habitats. The objectives were to identify deficiencies in rabies awareness, describe the occurrence of bat exposures, and explore factors associated with transdermal bat exposures. METHODS: A survey was administered to a convenience sample of adult guano miners, bat hunters, game wardens, and residents/personnel at Buddhist temples where mass bat roosting occurs. The questionnaire elicited information on demographics, experience with bat exposures, and rabies knowledge. Participants were also asked to describe actions they would take in response to a bat bite as well as actions for a bite from a potentially rabid animal. Bivariate analysis was used to compare responses between groups and multivariable logistic regression was used to explore factors independently associated with being bitten or scratched by a bat. FINDINGS: Of 106 people interviewed, 11 (10%) identified bats as a potential source of rabies. A history of a bat bite or scratch was reported by 29 (27%), and 38 (36%) stated either that they would do nothing or that they did not know what they would do in response to a bat bite. Guano miners were less likely than other groups to indicate animal bites as a mechanism of rabies transmission (68% vs. 90%, p = 0.03) and were less likely to say they would respond appropriately to a bat bite or scratch (61% vs. 27%, p = 0.003). Guano mining, bat hunting, and being in a bat cave or roost area more than 5 times a year were associated with history of a bat bite or scratch. CONCLUSIONS: These findings indicate the need for educational outreach to raise awareness of bat rabies, promote exposure prevention, and ensure appropriate health-seeking behaviors for bat-inflicted wounds, particularly among at-risk groups in Thailand.",2011 Jun 28,"['Robertson, Kis', 'Lumlertdacha, Boonlert', 'Franka, Richard', 'Petersen, Brett', 'Bhengsri, Saithip', 'Henchaichon, Sununta', 'Peruski, Leonard F.', 'Baggett, Henry C.', 'Maloney, Susan A.', 'Rupprecht, Charles E.']",PLoS Negl Trop Dis,,,True
16f4fcc0f008c01ee4711085e070b3dcb17040d4,PMC,"Host range, host specificity and hypothesized host shift events among viruses of lower vertebrates",http://dx.doi.org/10.1186/1297-9716-42-67,PMC3125225,21592358,CC BY,"The successful replication of a viral agent in a host is a complex process that often leads to a species specificity of the virus and can make interspecies transmission difficult. Despite this difficulty, natural host switch seems to have been frequent among viruses of lower vertebrates, especially fish viruses, since there are several viruses known to be able to infect a wide range of species. In the present review we will focus on well documented reports of broad host range, variations in host specificity, and host shift events hypothesized for viruses within the genera Ranavirus, Novirhabdovirus, Betanodavirus, Isavirus, and some herpesvirus.",2011 May 18,"['Bandín, Isabel', 'Dopazo, Carlos P']",Vet Res,,,True
d6cbaee69496b4617b6032c4b82cfc7afe601fac,PMC,Antibodies on demand: a fast method for the production of human scFvs with minimal amounts of antigen,http://dx.doi.org/10.1186/1472-6750-11-61,PMC3125328,21635725,CC BY,"BACKGROUND: Antibodies constitute a powerful tool to study protein function, protein localization and protein-protein interactions, as well as for diagnostic and therapeutic purposes. High-throughput antibody development requires faster methodologies with lower antigen consumption. RESULTS: Here, we describe a novel methodology to select human monoclonal recombinant antibodies by combining in vitro protein expression, phage display antibody libraries and antibody microarrays. The application of this combination of methodologies permitted us to generate human single-chain variable fragments (scFvs) against two proteins: green fluorescent protein (GFP) and thioredoxin (Trx) in a short time, using as low as 5 μg of purified protein. These scFvs showed specific reactivity against their respective targets and worked well by ELISA and western blot. The scFvs were able to recognise as low as 31 ng of protein of their respective targets by western blot. CONCLUSION: This work describes a novel and miniaturized methodology to obtain human monoclonal recombinant antibodies against any target in a shorter time than other methodologies using only 5 μg of protein. The protocol could be easily adapted to a high-throughput procedure for antibody production.",2011 Jun 2,"['Babel, Ingrid', 'Barderas, Rodrigo', 'Peláez-García, Alberto', 'Casal, J Ignacio']",BMC Biotechnol,,,True
fd521d37325a60e6ed92aa9bcf4541b9a68ee90e,PMC,Identification of CD8(+ )cytotoxic T lymphocyte epitopes from porcine reproductive and respiratory syndrome virus matrix protein in BALB/c mice,http://dx.doi.org/10.1186/1743-422X-8-263,PMC3126774,21619712,CC BY,"Twenty-seven nanopeptides derived from the matrix (M) protein of porcine reproductive and respiratory syndrome virus (PRRSV) were screened for their ability to elicit a recall interferon-γ (IFN-γ) response from the splenocytes of BALB/c mice following DNA vaccination and a booster vaccination with recombinant vaccinia virus rWR-PRRSV-M. We identified two peptides (amino acid residues K(93)FITSRCRL and F(57)GYMTFVHF) as CD8(+ )cytotoxic T lymphocyte (CTL) epitopes. These peptides elicited significant numbers of IFN-γ secreting cells, compared with other M nonapeptides and one irrelevant nonapeptide. Bioinformatics analysis showed that the former is an H-2K(d)-restricted CTL epitope, and the latter is an H-2D(d)-restricted CTL epitope. Multiple amino acid sequence alignment among different PRRSV M sequences submitted to GenBank indicated that these two CTL epitopes are strongly conserved, and they should therefore be considered for further research on the mechanisms of cellular immune responses to PRRSV.",2011 May 30,"['Zhang, Weijun', 'Lin, Yan', 'Bai, Yu', 'Tong, Tiegang', 'Wang, Qun', 'Liu, Nihong', 'Liu, Guangliang', 'Xiao, Yihong', 'Yang, Tao', 'Bu, Zhigao', 'Tong, Guangzhi', 'Wu, Donglai']",Virol J,,,True
fa2c978f246035c7e524e301c1ed8f9a5178dfde,PMC,Computer-based fluorescence quantification: a novel approach to study nucleolar biology,http://dx.doi.org/10.1186/1471-2121-12-25,PMC3126779,21639891,CC BY,"BACKGROUND: Nucleoli are composed of possibly several thousand different proteins and represent the most conspicuous compartments in the nucleus; they play a crucial role in the proper execution of many cellular processes. As such, nucleoli carry out ribosome biogenesis and sequester or associate with key molecules that regulate cell cycle progression, tumorigenesis, apoptosis and the stress response. Nucleoli are dynamic compartments that are characterized by a constant flux of macromolecules. Given the complex and dynamic composition of the nucleolar proteome, it is challenging to link modifications in nucleolar composition to downstream effects. RESULTS: In this contribution, we present quantitative immunofluorescence methods that rely on computer-based image analysis. We demonstrate the effectiveness of these techniques by monitoring the dynamic association of proteins and RNA with nucleoli under different physiological conditions. Thus, the protocols described by us were employed to study stress-dependent changes in the nucleolar concentration of endogenous and GFP-tagged proteins. Furthermore, our methods were applied to measure de novo RNA synthesis that is associated with nucleoli. We show that the techniques described here can be easily combined with automated high throughput screening (HTS) platforms, making it possible to obtain large data sets and analyze many of the biological processes that are located in nucleoli. CONCLUSIONS: Our protocols set the stage to analyze in a quantitative fashion the kinetics of shuttling nucleolar proteins, both at the single cell level as well as for a large number of cells. Moreover, the procedures described here are compatible with high throughput image acquisition and analysis using HTS automated platforms, thereby providing the basis to quantify nucleolar components and activities for numerous samples and experimental conditions. Together with the growing amount of information obtained for the nucleolar proteome, improvements in quantitative microscopy as they are described here can be expected to produce new insights into the complex biological functions that are orchestrated by the nucleolus.",2011 Jun 3,"['Kodiha, Mohamed', 'Bański, Piotr', 'Stochaj, Ursula']",BMC Cell Biol,,,True
79a70e09a449e41078a23b502c9a645a1e177eca,PMC,Is Network Clustering Detectable in Transmission Trees?,http://dx.doi.org/10.3390/v3060659,PMC3127449,21731813,CC BY,"Networks are often used to model the contact processes that allow pathogens to spread between hosts but it remains unclear which models best describe these networks. One question is whether clustering in networks, roughly defined as the propensity for triangles to form, affects the dynamics of disease spread. We perform a simulation study to see if there is a signal in epidemic transmission trees of clustering. We simulate susceptible-exposed-infectious-removed (SEIR) epidemics (with no re-infection) over networks with fixed degree sequences but different levels of clustering and compare trees from networks with the same degree sequence and different clustering levels. We find that the variation of such trees simulated on networks with different levels of clustering is barely greater than those simulated on networks with the same level of clustering, suggesting that clustering can not be detected in transmission data when re-infection does not occur.",2011 Jun 3,"Welch, David",Viruses,,,True
3f06c41154ff140670ba10f54eeaf640c39f29b9,PMC,Network Clustering Revealed the Systemic Alterations of Mitochondrial Protein Expression,http://dx.doi.org/10.1371/journal.pcbi.1002093,PMC3127811,21738461,CC BY,"The mitochondrial protein repertoire varies depending on the cellular state. Protein component modifications caused by mitochondrial DNA (mtDNA) depletion are related to a wide range of human diseases; however, little is known about how nuclear-encoded mitochondrial proteins (mt proteome) changes under such dysfunctional states. In this study, we investigated the systemic alterations of mtDNA-depleted (ρ(0)) mitochondria by using network analysis of gene expression data. By modularizing the quantified proteomics data into protein functional networks, systemic properties of mitochondrial dysfunction were analyzed. We discovered that up-regulated and down-regulated proteins were organized into two predominant subnetworks that exhibited distinct biological processes. The down-regulated network modules are involved in typical mitochondrial functions, while up-regulated proteins are responsible for mtDNA repair and regulation of mt protein expression and transport. Furthermore, comparisons of proteome and transcriptome data revealed that ρ(0) cells attempted to compensate for mtDNA depletion by modulating the coordinated expression/transport of mt proteins. Our results demonstrate that mt protein composition changed to remodel the functional organization of mitochondrial protein networks in response to dysfunctional cellular states. Human mt protein functional networks provide a framework for understanding how cells respond to mitochondrial dysfunctions.",2011 Jun 30,"['Jeon, Jouhyun', 'Jeong, Jae Hoon', 'Baek, Je-Hyun', 'Koo, Hyun-Jung', 'Park, Wook-Ha', 'Yang, Jae-Seong', 'Yu, Myeong-Hee', 'Kim, Sanguk', 'Pak, Youngmi Kim']",PLoS Comput Biol,,,True
b514652703a631715ca85e65499c66016fb994d4,PMC,Snowbirds and infection--new phenomena in pneumonia and influenza hospitalizations from winter migration of older adults: A spatiotemporal analysis,http://dx.doi.org/10.1186/1471-2458-11-444,PMC3128025,21649919,CC BY,"BACKGROUND: Despite advances in surveillance and prevention, pneumonia and influenza (P&I) remain among the leading causes of mortality in the United States. Elderly adults experience the most severe morbidity from influenza-associated diseases, and have the highest rates of seasonal migration within the U.S. compared to other subpopulations. The objective of this study is to assess spatiotemporal patterns in influenza-associated hospitalizations in the elderly, by time, geography, and intensity of P&I. Given the high seasonal migration of individuals to Florida, this state was examined more closely using harmonic regression to assess spatial and temporal patterns of P&I hospitalizations by state of residence. METHODS: Data containing all Medicare-eligible hospitalizations in the United States for 1991-2006 with P&I (ICD-9-CM codes 480-487) were abstracted for the 65+ population. Hospitalizations were classified by state of residence, provider state, and date of admissions, specifically comparing those admitted between October and March to those admitted between April and September. We then compared the hospitalization profile data of Florida residents with that of out-of-state residents by state of primary residence and time of year (in-season or out-of-season). RESULTS: We observed distinct seasonal patterns of nonresident P&I hospitalizations, especially comparing typical winter destination states, such as California, Arizona, Texas, and Florida, to other states. Although most other states generally experienced a higher proportion of non-resident P&I during the summer months (April-September), these states had higher nonresident P&I during the traditional peak influenza season (October-March). CONCLUSIONS: This study is among the first to quantify spatiotemporal P&I hospitalization patterns in the elderly, focusing on the change of patterns that are possibly due to seasonal population migration. Understanding migration and influenza-associated disease patterns in this vulnerable population is critical to prepare for and potentially prevent influenza outbreaks in this vulnerable population.",2011 Jun 7,"['Chui, Kenneth KH', 'Cohen, Steven A', 'Naumova, Elena N']",BMC Public Health,,,True
7025d7269f1bc09bfb96f51de30e2e0309a3fadc,PMC,Viral-bacterial co-infection in Australian Indigenous children with acute otitis media,http://dx.doi.org/10.1186/1471-2334-11-161,PMC3128050,21649905,CC BY,"BACKGROUND: Acute otitis media with perforation (AOMwiP) affects 40% of remote Indigenous children during the first 18 months of life. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the primary bacterial pathogens of otitis media and their loads predict clinical ear state. Our hypothesis is that antecedent respiratory viral infection increases bacterial density and progression to perforation. METHODS: A total of 366 nasopharyngeal swabs from 114 Indigenous children were retrospectively examined. A panel of 17 respiratory viruses was screened by PCR, and densities of S. pneumoniae, H. influenzae and M. catarrhalis were estimated by quantitative real time PCR. Data are reported by clinical ear state. RESULTS: M. catarrhalis (96%), H. influenzae (91%), S. pneumoniae (89%) and respiratory viruses (59%) were common; including rhinovirus (HRV) (38%), polyomavirus (HPyV) (14%), adenovirus (HAdV) (13%), bocavirus (HBoV) (8%) and coronavirus (HCoV) (4%). Geometric mean bacterial loads were significantly higher in children with acute otitis media (AOM) compared to children without evidence of otitis media. Children infected with HAdV were 3 times more likely (p < 0.001) to have AOM with or without perforation. CONCLUSION: This study confirms a positive association between nasopharyngeal bacterial load and clinical ear state, exacerbated by respiratory viruses, in Indigenous children. HAdV was independently associated with acute ear states.",2011 Jun 7,"['Binks, Michael J', 'Cheng, Allen C', 'Smith-Vaughan, Heidi', 'Sloots, Theo', 'Nissen, Michael', 'Whiley, David', 'McDonnell, Joseph', 'Leach, Amanda J']",BMC Infect Dis,,,True
95cff929be1b2765e78d6293e4722f404a814011,PMC,How to make predictions about future infectious disease risks,http://dx.doi.org/10.1098/rstb.2010.0387,PMC3130384,21624924,CC BY,"Formal, quantitative approaches are now widely used to make predictions about the likelihood of an infectious disease outbreak, how the disease will spread, and how to control it. Several well-established methodologies are available, including risk factor analysis, risk modelling and dynamic modelling. Even so, predictive modelling is very much the ‘art of the possible’, which tends to drive research effort towards some areas and away from others which may be at least as important. Building on the undoubted success of quantitative modelling of the epidemiology and control of human and animal diseases such as AIDS, influenza, foot-and-mouth disease and BSE, attention needs to be paid to developing a more holistic framework that captures the role of the underlying drivers of disease risks, from demography and behaviour to land use and climate change. At the same time, there is still considerable room for improvement in how quantitative analyses and their outputs are communicated to policy makers and other stakeholders. A starting point would be generally accepted guidelines for ‘good practice’ for the development and the use of predictive models.",2011 Jul 12,"Woolhouse, Mark",Philos Trans R Soc Lond B Biol Sci,,,True
7dc484e62b5a5e470b072184f55b023d5e751061,PMC,Ceacam1 Separates Graft-versus-Host-Disease from Graft-versus-Tumor Activity after Experimental Allogeneic Bone Marrow Transplantation,http://dx.doi.org/10.1371/journal.pone.0021611,PMC3130781,21760897,CC BY,"BACKGROUND: Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD). Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models. METHODS: We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models. In vivo, Ceacam1(−/−) T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi), CD62L(lo)). Additionally, Ceacam1(−/−) CD8 T cells had greater expression of the gut-trafficking integrin α(4)β(7), though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(−/−) recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(−/−) mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+) lymphoma model was improved in animals receiving Ceacam1(−/−) vs. control T cells. CONCLUSIONS: We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the donor graft and host tissues, this suggests that targeting Ceacam1 may represent a potent strategy for the regulation of GVHD and GVT after allogeneic transplantation.",2011 Jul 6,"['Lu, Sydney X.', 'Kappel, Lucy W.', 'Charbonneau-Allard, Anne-Marie', 'Atallah, Renée', 'Holland, Amanda M.', 'Turbide, Claire', 'Hubbard, Vanessa M.', 'Rotolo, Jimmy A.', 'Smith, Marsinay', 'Suh, David', 'King, Christopher', 'Rao, Uttam K.', 'Yim, Nury', 'Bautista, Johanne L.', 'Jenq, Robert R.', 'Penack, Olaf', 'Na, Il-Kang', 'Liu, Chen', 'Murphy, George', 'Alpdogan, Onder', 'Blumberg, Richard S.', 'Macian, Fernando', 'Holmes, Kathryn V.', 'Beauchemin, Nicole', 'van den Brink, Marcel R. M.']",PLoS One,,,True
06c0371d82953f5c35ee8bff3e5165d5aa1516de,PMC,Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection,http://dx.doi.org/10.1371/journal.ppat.1001347,PMC3131267,21750671,CC BY,"The inhibitory receptor programmed death-1 (PD-1) has the capacity to maintain peripheral tolerance and limit immunopathological damage; however, its precise role in fulminant viral hepatitis (FH) has yet to be described. Here, we investigated the functional mechanisms of PD-1 as related to FH pathogenesis induced by the murine hepatitis virus strain-3 (MHV-3). High levels of PD-1-positive CD4(+), CD8(+) T cells, NK cells and macrophages were observed in liver, spleen, lymph node and thymus tissues following MHV-3 infection. PD-1-deficient mice exhibited significantly higher expression of the effector molecule which initiates fibrinogen deposition, fibrinogen-like protein 2 (FGL2), than did their wild-type (WT) littermates. As a result, more severe tissue damage was produced and mortality rates were higher. Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection. Conversely, in vivo blockade of IFN-γ and TNF-α led to efficient inhibition of FGL2 expression, greatly attenuated the development of tissue lesions, and ultimately reduced mortality. Thus, the up-regulation of FGL2 in PD-1-deficient mice was determined to be mediated by IFN-γ and TNF-α. Taken together, our results suggest that PD-1 signaling plays an essential role in decreasing the immunopathological damage induced by MHV-3 and that manipulation of this signal might be a useful strategy for FH immunotherapy.",2011 Jul 7,"['Chen, Yongwen', 'Wu, Shengxi', 'Guo, Guoning', 'Fei, Lei', 'Guo, Sheng', 'Yang, Chengying', 'Fu, Xiaolan', 'Wu, Yuzhang']",PLoS Pathog,,,True
0c22edd80a03a1b9de7f3d29b729ad1006d10674,PMC,Machupo Virus Glycoprotein Determinants for Human Transferrin Receptor 1 Binding and Cell Entry,http://dx.doi.org/10.1371/journal.pone.0021398,PMC3131282,21750710,CC0,"Machupo virus (MACV) is a highly pathogenic New World arenavirus that causes hemorrhagic fever in humans. MACV, as well as other pathogenic New World arenaviruses, enter cells after their GP1 attachment glycoprotein binds to their cellular receptor, transferrin receptor 1 (TfR1). TfR1 residues essential for this interaction have been described, and a co-crystal of MACV GP1 bound to TfR1 suggests GP1 residues important for this association. We created MACV GP1 variants and tested their effect on TfR1 binding and virus entry to evaluate the functional significance of some of these and additional residues in human and simian cells. We found residues R111, D123, Y122, and F226 to be essential, D155, and P160 important, and D114, S116, D140, and K169 expendable for the GP1-TfR1 interaction and MACV entry. Several MACV GP1 residues that are critical for the interaction with TfR1 are conserved among other New World arenaviruses, indicating a common basis of receptor interaction. Our findings also open avenues for the rational development of viral entry inhibitors.",2011 Jul 7,"['Radoshitzky, Sheli R.', 'Longobardi, Lindsay E.', 'Kuhn, Jens H.', 'Retterer, Cary', 'Dong, Lian', 'Clester, Jeremiah C.', 'Kota, Krishna', 'Carra, John', 'Bavari, Sina']",PLoS One,,,True
7212e4cdbb493aa171b9d07c3946114d715f1e5b,PMC,GI-type T4SS-mediated horizontal transfer of the 89K pathogenicity island in epidemic Streptococcus suis serotype 2,http://dx.doi.org/10.1111/j.1365-2958.2011.07553.x,PMC3132442,21244532,CC BY,"Pathogenicity islands (PAIs), a distinct type of genomic island (GI), play important roles in the rapid adaptation and increased virulence of pathogens. 89K is a newly identified PAI in epidemic Streptococcus suis isolates that are related to the two recent large-scale outbreaks of human infection in China. However, its mechanism of evolution and contribution to the epidemic spread of S. suis 2 remain unknown. In this study, the potential for mobilization of 89K was evaluated, and its putative transfer mechanism was investigated. We report that 89K can spontaneously excise to form an extrachromosomal circular product. The precise excision is mediated by an 89K-borne integrase through site-specific recombination, with help from an excisionase. The 89K excision intermediate acts as a substrate for lateral transfer to non-89K S. suis 2 recipients, where it reintegrates site-specifically into the target site. The conjugal transfer of 89K occurred via a GI type IV secretion system (T4SS) encoded in 89K, at a frequency of 10(−6) transconjugants per donor. This is the first demonstration of horizontal transfer of a Gram-positive PAI mediated by a GI-type T4SS. We propose that these genetic events are important in the emergence, pathogenesis and persistence of epidemic S. suis 2 strains.",2011 Mar,"['Li, Ming', 'Shen, Xiaodong', 'Yan, Jinghua', 'Han, Huiming', 'Zheng, Beiwen', 'Liu, Di', 'Cheng, Hao', 'Zhao, Yan', 'Rao, Xiancai', 'Wang, Changjun', 'Tang, Jiaqi', 'Hu, Fuquan', 'Gao, George F']",Mol Microbiol,,,True
6cdc67641b41343d179febae3d95e5ce6fabcb21,PMC,GI-type T4SS-mediated horizontal transfer of the 89K pathogenicity island in epidemic Streptococcus suis serotype 2,http://dx.doi.org/10.1111/j.1365-2958.2011.07553.x,PMC3132442,21244532,CC BY,"Pathogenicity islands (PAIs), a distinct type of genomic island (GI), play important roles in the rapid adaptation and increased virulence of pathogens. 89K is a newly identified PAI in epidemic Streptococcus suis isolates that are related to the two recent large-scale outbreaks of human infection in China. However, its mechanism of evolution and contribution to the epidemic spread of S. suis 2 remain unknown. In this study, the potential for mobilization of 89K was evaluated, and its putative transfer mechanism was investigated. We report that 89K can spontaneously excise to form an extrachromosomal circular product. The precise excision is mediated by an 89K-borne integrase through site-specific recombination, with help from an excisionase. The 89K excision intermediate acts as a substrate for lateral transfer to non-89K S. suis 2 recipients, where it reintegrates site-specifically into the target site. The conjugal transfer of 89K occurred via a GI type IV secretion system (T4SS) encoded in 89K, at a frequency of 10(−6) transconjugants per donor. This is the first demonstration of horizontal transfer of a Gram-positive PAI mediated by a GI-type T4SS. We propose that these genetic events are important in the emergence, pathogenesis and persistence of epidemic S. suis 2 strains.",2011 Mar,"['Li, Ming', 'Shen, Xiaodong', 'Yan, Jinghua', 'Han, Huiming', 'Zheng, Beiwen', 'Liu, Di', 'Cheng, Hao', 'Zhao, Yan', 'Rao, Xiancai', 'Wang, Changjun', 'Tang, Jiaqi', 'Hu, Fuquan', 'Gao, George F']",Mol Microbiol,,,False
b470eec84fd5bb0a9a7079506df05c3cdf398832,PMC,Cross-Reactive Human IgM-Derived Monoclonal Antibodies that Bind to HIV-1 Envelope Glycoproteins,http://dx.doi.org/10.3390/v2020547,PMC3133461,21755021,CC BY,"Elicitation of antibodies with potent and broad neutralizing activity against HIV by immunization remains a challenge. Several monoclonal antibodies (mAbs) isolated from humans with HIV-1 infection exhibit such activity but vaccine immunogens based on structures containing their epitopes have not been successful for their elicitation. All known broadly neutralizing mAbs (bnmAbs) are immunoglobulin (Ig) Gs (IgGs) and highly somatically hypermutated which could impede their elicitation. Ig Ms (IgMs) are on average significantly less divergent from germline antibodies and are relevant for the development of vaccine immunogens but are underexplored compared to IgGs. Here we describe the identification and characterization of several human IgM-derived mAbs against HIV-1 which were selected from a large phage-displayed naive human antibody library constructed from blood, lymph nodes and spleens of 59 healthy donors. These antibodies bound with high affinity to recombinant envelope glycoproteins (gp140s, Envs) of HIV-1 isolates from different clades. They enhanced or did not neutralize infection by some of the HIV-1 primary isolates using CCR5 as a coreceptor but neutralized all CXCR4 isolates tested although weakly. One of these antibodies with relatively low degree of somatic hypermutation was more extensively characterized. It bound to a highly conserved region partially overlapping with the coreceptor binding site and close to but not overlapping with the CD4 binding site. These results suggest the existence of conserved structures that could direct the immune response to non-neutralizing or even enhancing antibodies which may represent a strategy used by the virus to escape neutralizing immune responses. Further studies will show whether such a strategy plays a role in HIV infection of humans, how important that role could be, and what the mechanisms of infection enhancement are. The newly identified mAbs could be used as reagents to further characterize conserved non-neutralizing, weakly neutralizing or enhancing epitopes and modify or remove them from candidate vaccine immunogens.",2010 Feb 4,"['Chen, Weizao', 'Zhu, Zhongyu', 'Liao, Huaxin', 'Quinnan, Gerald V.', 'Broder, Christopher C.', 'Haynes, Barton F.', 'Dimitrov, Dimiter S.']",Viruses,,,True
6fe5d96d6e7a93c94a8788af735bdc919cd8d71d,PMC,A Conformation-Sensitive Monoclonal Antibody against the A2 Domain of von Willebrand Factor Reduces Its Proteolysis by ADAMTS13,http://dx.doi.org/10.1371/journal.pone.0022157,PMC3133621,21779388,CC BY,"The size of von Willebrand factor (VWF), controlled by ADAMTS13-dependent proteolysis, is associated with its hemostatic activity. Many factors regulate ADAMTS13-dependent VWF proteolysis through their interaction with VWF. These include coagulation factor VIII, platelet glycoprotein 1bα, and heparin sulfate, which accelerate the cleavage of VWF. Conversely, thrombospondin-1 decreases the rate of VWF proteolysis by ADAMTS13 by competing with ADAMTS13 for the A3 domain of VWF. To investigate whether murine monoclonal antibodies (mAbs) against human VWF affect the susceptibility of VWF to proteolysis by ADAMTS13 in vitro, eight mAbs to different domains of human VWF were used to evaluate the effects on VWF cleavage by ADAMTS13 under fluid shear stress and static/denaturing conditions. Additionally, the epitope of anti-VWF mAb (SZ34) was mapped using recombinant proteins in combination with enzyme-linked immunosorbent assay and Western blot analysis. The results indicate that mAb SZ34 inhibited proteolytic cleavage of VWF by ADAMTS13 in a concentration-dependent manner under fluid shear stress, but not under static/denaturing conditions. The binding epitope of SZ34 mAb is located between A1555 and G1595 in the central A2 domain of VWF. These data show that an anti-VWF mAb against the VWF-A2 domain (A1555-G1595) reduces the proteolytic cleavage of VWF by ADAMTS13 under shear stress, suggesting the role of this region in interaction with ADAMTS13.",2011 Jul 11,"['Zhang, Jingyu', 'Ma, Zhenni', 'Dong, Ningzheng', 'Liu, Fang', 'Su, Jian', 'Zhao, Yiming', 'Shen, Fei', 'Wang, Anyou', 'Ruan, Changgeng']",PLoS One,,,True
f7185938312bfa794681998fe0bff4e2697c053d,PMC,An Overview on the Field of Micro- and Nanotechnologies for Synthetic Peptide-Based Vaccines,http://dx.doi.org/10.1155/2011/181646,PMC3134826,21773041,CC BY,"The development of synthetic peptide-based vaccines has many advantages in comparison with vaccines based on live attenuated organisms, inactivated or killed organism, or toxins. Peptide-based vaccines cannot revert to a virulent form, allow a better conservation, and are produced more easily and safely. However, they generate a weaker immune response than other vaccines, and the inclusion of adjuvants and/or the use of vaccine delivery systems is almost always needed. Among vaccine delivery systems, micro- and nanoparticulated ones are attractive, because their particulate nature can increase cross-presentation of the peptide. In addition, they can be passively or actively targeted to antigen presenting cells. Furthermore, particulate adjuvants are able to directly activate innate immune system in vivo. Here, we summarize micro- and nanoparticulated vaccine delivery systems used in the field of synthetic peptide-based vaccines as well as strategies to increase their immunogenicity.",2011 Jun 15,"['Salvador, Aiala', 'Igartua, Manoli', 'Hernández, Rosa Maria', 'Pedraz, José Luis']",J Drug Deliv,,,True
f81a3ef89c4144309cf86374440e2a3a8a0e095c,PMC,Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony,http://dx.doi.org/10.1371/journal.ppat.1002155,PMC3136464,21779173,CC BY,"Adenoviruses are DNA viruses that naturally infect many vertebrates, including humans and monkeys, and cause a wide range of clinical illnesses in humans. Infection from individual strains has conventionally been thought to be species-specific. Here we applied the Virochip, a pan-viral microarray, to identify a novel adenovirus (TMAdV, titi monkey adenovirus) as the cause of a deadly outbreak in a closed colony of New World monkeys (titi monkeys; Callicebus cupreus) at the California National Primate Research Center (CNPRC). Among 65 titi monkeys housed in a building, 23 (34%) developed upper respiratory symptoms that progressed to fulminant pneumonia and hepatitis, and 19 of 23 monkeys, or 83% of those infected, died or were humanely euthanized. Whole-genome sequencing of TMAdV revealed that this adenovirus is a new species and highly divergent, sharing <57% pairwise nucleotide identity with other adenoviruses. Cultivation of TMAdV was successful in a human A549 lung adenocarcinoma cell line, but not in primary or established monkey kidney cells. At the onset of the outbreak, the researcher in closest contact with the monkeys developed an acute respiratory illness, with symptoms persisting for 4 weeks, and had a convalescent serum sample seropositive for TMAdV. A clinically ill family member, despite having no contact with the CNPRC, also tested positive, and screening of a set of 81 random adult blood donors from the Western United States detected TMAdV-specific neutralizing antibodies in 2 individuals (2/81, or 2.5%). These findings raise the possibility of zoonotic infection by TMAdV and human-to-human transmission of the virus in the population. Given the unusually high case fatality rate from the outbreak (83%), it is unlikely that titi monkeys are the native host species for TMAdV, and the natural reservoir of the virus is still unknown. The discovery of TMAdV, a novel adenovirus with the capacity to infect both monkeys and humans, suggests that adenoviruses should be monitored closely as potential causes of cross-species outbreaks.",2011 Jul 14,"['Chen, Eunice C.', 'Yagi, Shigeo', 'Kelly, Kristi R.', 'Mendoza, Sally P.', 'Maninger, Nicole', 'Rosenthal, Ann', 'Spinner, Abigail', 'Bales, Karen L.', 'Schnurr, David P.', 'Lerche, Nicholas W.', 'Chiu, Charles Y.']",PLoS Pathog,,,True
5c364a85b8e920e9b4ad2fa201589fc319bc174b,PMC,Interplay between SIN3A and STAT3 Mediates Chromatin Conformational Changes and GFAP Expression during Cellular Differentiation,http://dx.doi.org/10.1371/journal.pone.0022018,PMC3136934,21779366,CC BY,"BACKGROUND: Neurons and astrocytes are generated from common neural precursors, yet neurogenesis precedes astrocyte formation during embryogenesis. The mechanisms of neural development underlying suppression and de-suppression of differentiation- related genes for cell fate specifications are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: By using an in vitro system in which NTera-2 cells were induced to differentiate into an astrocyte-like lineage, we revealed a novel role for Sin3A in maintaining the suppression of GFAP in NTera-2 cells. Sin3A coupled with MeCP2 bound to the GFAP promoter and their occupancies were correlated with repression of GFAP transcription. The repression by Sin3A and MeCP2 may be an essential mechanism underlying the inhibition of cell differentiation. Upon commitment toward an astrocyte-like lineage, Sin3A- MeCP2 departed from the promoter and activated STAT3 simultaneously bound to the promoter and exon 1 of GFAP; meanwhile, olig2 was exported from nuclei to the cytoplasm. This suggested that a three-dimensional or higher-order structure was provoked by STAT3 binding between the promoter and proximal coding regions. STAT3 then recruited CBP/p300 to exon 1 and targeted the promoter for histone H3K9 and H3K14 acetylation. The CBP/p300-mediated histone modification further facilitates chromatin remodeling, thereby enhancing H3K4 trimethylation and recruitment of RNA polymerase II to activate GFAP gene transcription. CONCLUSIONS/SIGNIFICANCE: These results provide evidence that exchange of repressor and activator complexes and epigenetic modifications are critical strategies for cellular differentiation and lineage-specific gene expression.",2011 Jul 11,"['Cheng, Pei-Yi', 'Lin, Yu-Ping', 'Chen, Ya-Ling', 'Lee, Yi-Ching', 'Tai, Chia-Chen', 'Wang, Yi-Ting', 'Chen, Yu-Ju', 'Kao, Cheng-Fu', 'Yu, John']",PLoS One,,,True
d87f44c7d76e4c51ed8e72103669c275e2db3e71,PMC,Milk Lacking α-Casein Leads to Permanent Reduction in Body Size in Mice,http://dx.doi.org/10.1371/journal.pone.0021775,PMC3138747,21789179,CC BY,"The major physiological function of milk is the transport of amino acids, carbohydrates, lipids and minerals to mammalian offspring. Caseins, the major milk proteins, are secreted in the form of a micelle consisting of protein and calcium-phosphate. We have analysed the role of the milk protein α-casein by inactivating the corresponding gene in mice. Absence of α-casein protein significantly curtails secretion of other milk proteins and calcium-phosphate, suggesting a role for α-casein in the establishment of casein micelles. In contrast, secretion of albumin, which is not synthesized in the mammary epithelium, into milk is not reduced. The absence of α-casein also significantly inhibits transcription of the other casein genes. α-Casein deficiency severely delays pup growth during lactation and results in a life-long body size reduction compared to control animals, but has only transient effects on physical and behavioural development of the pups. The data support a critical role for α-casein in casein micelle assembly. The results also confirm lactation as a critical window of metabolic programming and suggest milk protein concentration as a decisive factor in determining adult body weight.",2011 Jul 18,"['Kolb, Andreas F.', 'Huber, Reinhard C.', 'Lillico, Simon G.', 'Carlisle, Ailsa', 'Robinson, Claire J.', 'Neil, Claire', 'Petrie, Linda', 'Sorensen, Dorte B.', 'Olsson, I. Anna S.', 'Whitelaw, C. Bruce A.']",PLoS One,,,True
b5e8c704bc997577cfb950adffa06c7019aacf4a,PMC,Discovery of a small arterivirus gene that overlaps the GP5 coding sequence and is important for virus production,http://dx.doi.org/10.1099/vir.0.029264-0,PMC3139419,21307223,CC BY,"The arterivirus family (order Nidovirales) of single-stranded, positive-sense RNA viruses includes porcine respiratory and reproductive syndrome virus and equine arteritis virus (EAV). Their replicative enzymes are translated from their genomic RNA, while their seven structural proteins are encoded by a set of small, partially overlapping genes in the genomic 3′-proximal region. The latter are expressed via synthesis of a set of subgenomic mRNAs that, in general, are functionally monocistronic (except for a bicistronic mRNA encoding the E and GP2 proteins). ORF5, which encodes the major glycoprotein GP5, has been used extensively for phylogenetic analyses. However, an in-depth computational analysis now reveals the arterivirus-wide conservation of an additional AUG-initiated ORF, here termed ORF5a, that overlaps the 5′ end of ORF5. The pattern of substitutions across sequence alignments indicated that ORF5a is subject to functional constraints at the amino acid level, while an analysis of substitutions at synonymous sites in ORF5 revealed a greatly reduced frequency of substitution in the portion of ORF5 that is overlapped by ORF5a. The 43–64 aa ORF5a protein and GP5 are probably expressed from the same subgenomic mRNA, via a translation initiation mechanism involving leaky ribosomal scanning. Inactivation of ORF5a expression by reverse genetics yielded a severely crippled EAV mutant, which displayed lower titres and a tiny plaque phenotype. These defects, which could be partially complemented in ORF5a-expressing cells, indicate that the novel protein, which may be the eighth structural protein of arteriviruses, is expressed and important for arterivirus infection.",2011 May,"['Firth, Andrew E.', 'Zevenhoven-Dobbe, Jessika C.', 'Wills, Norma M.', 'Go, Yun Young', 'Balasuriya, Udeni B. R.', 'Atkins, John F.', 'Snijder, Eric J.', 'Posthuma, Clara C.']",J Gen Virol,,,True
1d8b7f079d5b7a6f9ecd1a0999f16582df84fd8e,PMC,NTPase and 5′-RNA Triphosphatase Activities of Chikungunya Virus nsP2 Protein,http://dx.doi.org/10.1371/journal.pone.0022336,PMC3139623,21811589,CC BY,"Chikungunya virus (CHIKV) is an insect borne virus (genus: Alphavirus) which causes acute febrile illness in humans followed by a prolonged arthralgic disease that affects the joints of the extremities. Re-emergence of the virus in the form of outbreaks in last 6–7 years has posed a serious public health problem. CHIKV has a positive sense single stranded RNA genome of about 12,000 nt. Open reading frame 1 of the viral genome encodes a polyprotein precursor, nsP1234, which is processed further into different non structural proteins (nsP1, nsP2, nsP3 and nsP4). Sequence based analyses have shown helicase domain at the N-terminus and protease domain at C-terminus of nsP2. A detailed biochemical analysis of NTPase/RNA helicase and 5′-RNA phosphatase activities of recombinant CHIKV-nsP2T protein (containing conserved NTPase/helicase motifs in the N-terminus and partial papain like protease domain at the C-terminus) was carried out. The protein could hydrolyze all NTPs except dTTP and showed better efficiency for ATP, dATP, GTP and dGTP hydrolysis. ATP was the most preferred substrate by the enzyme. CHIKV-nsP2T also showed 5′-triphosphatase (RTPase) activity that specifically removes the γ-phosphate from the 5′ end of RNA. Both NTPase and RTPase activities of the protein were completely dependent on Mg(2+) ions. RTPase activity was inhibited by ATP showing sharing of the binding motif by NTP and RNA. Both enzymatic activities were drastically reduced by mutations in the NTP binding motif (GKT) and co-factor, Mg(2+) ion binding motif (DEXX) suggesting that they have a common catalytic site.",2011 Jul 19,"['Karpe, Yogesh A.', 'Aher, Pankaj P.', 'Lole, Kavita S.']",PLoS One,,,True
fd9051e7bcf001955cb7625a5b2c51ddf58218dc,PMC,Interferon Production and Signaling Pathways Are Antagonized during Henipavirus Infection of Fruit Bat Cell Lines,http://dx.doi.org/10.1371/journal.pone.0022488,PMC3139658,21811620,CC BY,"Bats are natural reservoirs for a spectrum of infectious zoonotic diseases including the recently emerged henipaviruses (Hendra and Nipah viruses). Henipaviruses have been observed both naturally and experimentally to cause serious and often fatal disease in many different mammal species, including humans. Interestingly, infection of the flying fox with henipaviruses occurs in the absence of clinical disease. The extreme variation in the disease pattern between humans and bats has led to an investigation into the effects of henipavirus infection on the innate immune response in bat cell lines. We report that henipavirus infection does not result in the induction of interferon expression, and the viruses also inhibit interferon signaling. We also confirm that the interferon production and signaling block in bat cells is not due to differing viral protein expression levels between human and bat hosts. This information, in addition to the known lack of clinical signs in bats following henipavirus infection, suggests that bats control henipavirus infection by an as yet unidentified mechanism, not via the interferon response. This is the first report of henipavirus infection in bat cells specifically investigating aspects of the innate immune system.",2011 Jul 19,"['Virtue, Elena R.', 'Marsh, Glenn A.', 'Baker, Michelle L.', 'Wang, Lin-Fa']",PLoS One,,,True
c754ce4a15d6efa184842b77848e34d04445e209,PMC,Parasites or Cohabitants: Cruel Omnipresent Usurpers or Creative “Éminences Grises”?,http://dx.doi.org/10.1155/2011/214174,PMC3140032,21785696,CC BY,"This paper presents many types of interplays between parasites and the host, showing the history of parasites, the effects of parasites on the outcome of wars, invasions, migrations, and on the development of numerous regions of the globe, and the impact of parasitic diseases on the society and on the course of human evolution. It also emphasizes the pressing need to change the look at the parasitism phenomenon, proposing that the term “cohabitant” is more accurate than parasite, because every living being, from bacteria to mammals, is a consortium of living beings in the pangenome. Even the term parasitology should be replaced by cohabitology because there is no parasite alone and host alone: both together compose a new adaptive system: the parasitized-host or the cohabitant-cohabited being. It also suggests switching the old paradigm based on attrition and destruction, to a new one founded on adaptation and living together.",2011 Jul 18,"['Vannier-Santos, Marcos A.', 'Lenzi, Henrique L.']",J Parasitol Res,,,True
57ef6bf1ad8360243bf77eb91ed13430e42b35e1,PMC,Microbial Virulence as an Emergent Property: Consequences and Opportunities,http://dx.doi.org/10.1371/journal.ppat.1002136,PMC3141035,21814511,CC BY,,2011 Jul 21,"['Casadevall, Arturo', 'Fang, Ferric C.', 'Pirofski, Liise-anne']",PLoS Pathog,,,True
8ef53001824bab46d02f6968b8ee1a148a7406d9,PMC,Global mRNA Degradation during Lytic Gammaherpesvirus Infection Contributes to Establishment of Viral Latency,http://dx.doi.org/10.1371/journal.ppat.1002150,PMC3141057,21811408,CC BY,"During a lytic gammaherpesvirus infection, host gene expression is severely restricted by the global degradation and altered 3′ end processing of mRNA. This host shutoff phenotype is orchestrated by the viral SOX protein, yet its functional significance to the viral lifecycle has not been elucidated, in part due to the multifunctional nature of SOX. Using an unbiased mutagenesis screen of the murine gammaherpesvirus 68 (MHV68) SOX homolog, we isolated a single amino acid point mutant that is selectively defective in host shutoff activity. Incorporation of this mutation into MHV68 yielded a virus with significantly reduced capacity for mRNA turnover. Unexpectedly, the MHV68 mutant showed little defect during the acute replication phase in the mouse lung. Instead, the virus exhibited attenuation at later stages of in vivo infections suggestive of defects in both trafficking and latency establishment. Specifically, mice intranasally infected with the host shutoff mutant accumulated to lower levels at 10 days post infection in the lymph nodes, failed to develop splenomegaly, and exhibited reduced viral DNA levels and a lower frequency of latently infected splenocytes. Decreased latency establishment was also observed upon infection via the intraperitoneal route. These results highlight for the first time the importance of global mRNA degradation during a gammaherpesvirus infection and link an exclusively lytic phenomenon with downstream latency establishment.",2011 Jul 21,"['Richner, Justin M.', 'Clyde, Karen', 'Pezda, Andrea C.', 'Cheng, Benson Yee Hin', 'Wang, Tina', 'Kumar, G. Renuka', 'Covarrubias, Sergio', 'Coscoy, Laurent', 'Glaunsinger, Britt']",PLoS Pathog,,,True
795711186071a762e389ea991737dbc51abf8d41,PMC,Global mRNA Degradation during Lytic Gammaherpesvirus Infection Contributes to Establishment of Viral Latency,http://dx.doi.org/10.1371/journal.ppat.1002150,PMC3141057,21811408,CC BY,"During a lytic gammaherpesvirus infection, host gene expression is severely restricted by the global degradation and altered 3′ end processing of mRNA. This host shutoff phenotype is orchestrated by the viral SOX protein, yet its functional significance to the viral lifecycle has not been elucidated, in part due to the multifunctional nature of SOX. Using an unbiased mutagenesis screen of the murine gammaherpesvirus 68 (MHV68) SOX homolog, we isolated a single amino acid point mutant that is selectively defective in host shutoff activity. Incorporation of this mutation into MHV68 yielded a virus with significantly reduced capacity for mRNA turnover. Unexpectedly, the MHV68 mutant showed little defect during the acute replication phase in the mouse lung. Instead, the virus exhibited attenuation at later stages of in vivo infections suggestive of defects in both trafficking and latency establishment. Specifically, mice intranasally infected with the host shutoff mutant accumulated to lower levels at 10 days post infection in the lymph nodes, failed to develop splenomegaly, and exhibited reduced viral DNA levels and a lower frequency of latently infected splenocytes. Decreased latency establishment was also observed upon infection via the intraperitoneal route. These results highlight for the first time the importance of global mRNA degradation during a gammaherpesvirus infection and link an exclusively lytic phenomenon with downstream latency establishment.",2011 Jul 21,"['Richner, Justin M.', 'Clyde, Karen', 'Pezda, Andrea C.', 'Cheng, Benson Yee Hin', 'Wang, Tina', 'Kumar, G. Renuka', 'Covarrubias, Sergio', 'Coscoy, Laurent', 'Glaunsinger, Britt']",PLoS Pathog,,,False
23acad3bdcee7563f22da647aae639dbee1d56e6,PMC,Equal Graph Partitioning on Estimated Infection Network as an Effective Epidemic Mitigation Measure,http://dx.doi.org/10.1371/journal.pone.0022124,PMC3142118,21799777,CC BY,"Controlling severe outbreaks remains the most important problem in infectious disease area. With time, this problem will only become more severe as population density in urban centers grows. Social interactions play a very important role in determining how infectious diseases spread, and organization of people along social lines gives rise to non-spatial networks in which the infections spread. Infection networks are different for diseases with different transmission modes, but are likely to be identical or highly similar for diseases that spread the same way. Hence, infection networks estimated from common infections can be useful to contain epidemics of a more severe disease with the same transmission mode. Here we present a proof-of-concept study demonstrating the effectiveness of epidemic mitigation based on such estimated infection networks. We first generate artificial social networks of different sizes and average degrees, but with roughly the same clustering characteristic. We then start SIR epidemics on these networks, censor the simulated incidences, and use them to reconstruct the infection network. We then efficiently fragment the estimated network by removing the smallest number of nodes identified by a graph partitioning algorithm. Finally, we demonstrate the effectiveness of this targeted strategy, by comparing it against traditional untargeted strategies, in slowing down and reducing the size of advancing epidemics.",2011 Jul 22,"['Hadidjojo, Jeremy', 'Cheong, Siew Ann']",PLoS One,,,True
80a8911f3ccc06ddfc7581569014032487688283,PMC,Reference gene selection for gene expression studies using RT-qPCR in virus-infected planthoppers,http://dx.doi.org/10.1186/1743-422X-8-308,PMC3142240,21679431,CC BY,"BACKGROUND: Planthoppers not only severely affect crops by causing mechanical damage when feeding but are also vectors of several plant virus species. The analysis of gene expression in persistently infected planthoppers might unveil the molecular basis of viral transmission. Quantitative real-time RT-PCR (RT-qPCR) is currently the most accurate and sensitive method used for quantitative gene expression analysis. In order to normalize the resulting quantitative data, reference genes with constant expression during the experimental procedures are needed. RESULTS: Partial sequences of the commonly used reference genes actin (ACT), α1-tubulin (TUB), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), elongation factor 1 alpha (EF1A), ribosomal protein S18 (RPS18) and polyubiquitin C (UBI) from Delphacodes kuscheli, a planthopper capable of persistently transmitting the plant fijivirus Mal de Río Cuarto virus (MRCV), were isolated for the first time. Specific RT-qPCR primers were designed and the expression stability of these genes was assayed in MRCV-infective and naïve planthoppers using geNorm, Normfinder and BestKeeper tools. The overall analysis showed that UBI, followed by 18S and ACT, are the most suitable genes as internal controls for quantitative gene expression studies in MRCV-infective planthoppers, while TUB and EF1A are the most variable ones. Moreover, EF1A was upregulated by MRCV infection. CONCLUSIONS: A RT-qPCR platform for gene expression analysis in the MRCV-infected planthopper vector Delphacodes kuscheli was developed. Our work is the first report on reference gene selection in virus-infected insects, and might serve as a precedent for future gene expression studies on MRCV and other virus-planthopper pathosystems.",2011 Jun 16,"['Maroniche, Guillermo A', 'Sagadín, Mónica', 'Mongelli, Vanesa C', 'Truol, Graciela A', 'del Vas, Mariana']",Virol J,,,True
e1406defdf36c0e9507a509d880dd7df0ed84f56,PMC,On the Treatment of Airline Travelers in Mathematical Models,http://dx.doi.org/10.1371/journal.pone.0022151,PMC3143116,21799782,CC0,"The global spread of infectious diseases is facilitated by the ability of infected humans to travel thousands of miles in short time spans, rapidly transporting pathogens to distant locations. Mathematical models of the actual and potential spread of specific pathogens can assist public health planning in the case of such an event. Models should generally be parsimonious, but must consider all potentially important components of the system to the greatest extent possible. We demonstrate and discuss important assumptions relative to the parameterization and structural treatment of airline travel in mathematical models. Among other findings, we show that the most common structural treatment of travelers leads to underestimation of the speed of spread and that connecting travel is critical to a realistic spread pattern. Models involving travelers can be improved significantly by relatively simple structural changes but also may require further attention to details of parameterization.",2011 Jul 25,"['Johansson, Michael A.', 'Arana-Vizcarrondo, Neysarí', 'Biggerstaff, Brad J.', 'Staples, J. Erin', 'Gallagher, Nancy', 'Marano, Nina']",PLoS One,,,True
1fb48248ba087b62ed753f63f4ff046e68828bf9,PMC,Redesigning a large school-based clinical trial in response to changes in community practice,http://dx.doi.org/10.1177/1740774511403513,PMC3145214,21730079,CC BY,"Background Asthma exacerbations are seasonal with the greatest risk in elementary-age students occurring shortly after returning to school following summer break. Recent research suggests that this seasonality in children is primarily related to viral respiratory tract infections. Regular hand washing is the most effective method to prevent the spread of viral respiratory infections; unfortunately, achieving hand washing recommendations in schools is difficult. Therefore, we designed a study to evaluate the effect of hand sanitizer use in elementary schools on exacerbations among children with asthma. Purpose To describe the process of redesigning the trial in response to changes in the safety profile of the hand sanitizer as well as changes in hand hygiene practice in the schools. Methods The original trial was a randomized, longitudinal, subject-blinded, placebo-controlled, community-based crossover trial. The primary aim was to evaluate the incremental effectiveness of hand sanitizer use in addition to usual hand hygiene practices to decrease asthma exacerbations in elementary-age children. Three events occurred that required major modifications to the original study protocol: (1) safety concerns arose regarding the hand sanitizer’s active ingredient; (2) no substitute placebo hand sanitizer was available; and (3) community preferences changed regarding hand hygiene practices in the schools. Results The revised protocol is a randomized, longitudinal, community-based crossover trial. The primary aim is to evaluate the incremental effectiveness of a two-step hand hygiene process (hand hygiene education plus institutionally provided alcohol-based hand sanitizer) versus usual care to decrease asthma exacerbations. Enrollment was completed in May 2009 with 527 students from 30 schools. The intervention began in August 2009 and will continue through May 2011. Study results should be available at the end of 2011. Limitations The changed design does not allow us to directly measure the effectiveness of hand sanitizer use as a supplement to traditional hand washing practices. Conclusions The need to balance a rigorous study design with one that is acceptable to the community requires investigators to be actively involved with community collaborators and able to adapt study protocols to fit changing community practices.",2011 Jun,"['Gerald, Lynn B', 'Gerald, Joe K', 'McClure, Leslie A', 'Harrington, Kathy', 'Erwin, Sue', 'Bailey, William C']",Clin Trials,,,True
f9572dc31ce0512cc966d43fbe693656af18a03c,PMC,Immunity Traits in Pigs: Substantial Genetic Variation and Limited Covariation,http://dx.doi.org/10.1371/journal.pone.0022717,PMC3146468,21829490,CC BY,"BACKGROUND: Increasing robustness via improvement of resistance to pathogens is a major selection objective in livestock breeding. As resistance traits are difficult or impossible to measure directly, potential indirect criteria are measures of immune traits (ITs). Our underlying hypothesis is that levels of ITs with no focus on specific pathogens define an individual's immunocompetence and thus predict response to pathogens in general. Since variation in ITs depends on genetic, environmental and probably epigenetic factors, our aim was to estimate the relative importance of genetics. In this report, we present a large genetic survey of innate and adaptive ITs in pig families bred in the same environment. METHODOLOGY/PRINCIPAL FINDINGS: Fifty four ITs were studied on 443 Large White pigs vaccinated against Mycoplasma hyopneumoniae and analyzed by combining a principal component analysis (PCA) and genetic parameter estimation. ITs include specific and non specific antibodies, seric inflammatory proteins, cell subsets by hemogram and flow cytometry, ex vivo production of cytokines (IFNα, TNFα, IL6, IL8, IL12, IFNγ, IL2, IL4, IL10), phagocytosis and lymphocyte proliferation. While six ITs had heritabilities that were weak or not significantly different from zero, 18 and 30 ITs had moderate (0.10.4) heritability values, respectively. Phenotypic and genetic correlations between ITs were weak except for a few traits that mostly include cell subsets. PCA revealed no cluster of innate or adaptive ITs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that variation in many innate and adaptive ITs is genetically controlled in swine, as already reported for a smaller number of traits by other laboratories. A limited redundancy of the traits was also observed confirming the high degree of complementarity between innate and adaptive ITs. Our data provide a genetic framework for choosing ITs to be included as selection criteria in multitrait selection programmes that aim to improve both production and health traits.",2011 Jul 29,"['Flori, Laurence', 'Gao, Yu', 'Laloë, Denis', 'Lemonnier, Gaëtan', 'Leplat, Jean-Jacques', 'Teillaud, Angélique', 'Cossalter, Anne-Marie', 'Laffitte, Joëlle', 'Pinton, Philippe', 'de Vaureix, Christiane', 'Bouffaud, Marcel', 'Mercat, Marie-José', 'Lefèvre, François', 'Oswald, Isabelle P.', 'Bidanel, Jean-Pierre', 'Rogel-Gaillard, Claire']",PLoS One,,,True
f87f39187b751fafb24dad2685376da7c78f79e2,PMC,Accelerating vaccine development and deployment: report of a Royal Society satellite meeting,http://dx.doi.org/10.1098/rstb.2011.0100,PMC3146780,21893549,CC BY,"The Royal Society convened a meeting on the 17th and 18th November 2010 to review the current ways in which vaccines are developed and deployed, and to make recommendations as to how each of these processes might be accelerated. The meeting brought together academics, industry representatives, research sponsors, regulators, government advisors and representatives of international public health agencies from a broad geographical background. Discussions were held under Chatham House rules. High-throughput screening of new vaccine antigens and candidates was seen as a driving force for vaccine discovery. Multi-stakeholder, small-scale manufacturing facilities capable of rapid production of clinical grade vaccines are currently too few and need to be expanded. In both the human and veterinary areas, there is a need for tiered regulatory standards, differentially tailored for experimental and commercial vaccines, to allow accelerated vaccine efficacy testing. Improved cross-fertilization of knowledge between industry and academia, and between human and veterinary vaccine developers, could lead to more rapid application of promising approaches and technologies to new product development. Identification of best-practices and development of checklists for product development plans and implementation programmes were seen as low-cost opportunities to shorten the timeline for vaccine progression from the laboratory bench to the people who need it.",2011 Oct 12,"['Bregu, Migena', 'Draper, Simon J.', 'Hill, Adrian V. S.', 'Greenwood, Brian M.']",Philos Trans R Soc Lond B Biol Sci,,,False
c7f717457621e576d69c56b61d9ad9bd52a8a8b5,PMC,"During the summer 2009 outbreak of ""swine flu"" in Scotland what respiratory pathogens were diagnosed as H1N1/2009?",http://dx.doi.org/10.1186/1471-2334-11-192,PMC3146830,21752259,CC BY,"BACKGROUND: During the April-July 2009 outbreak of H1N1/2009 in scotland the West of Scotland Specialist Virology Centre (WoSSVC) in Glasgow tested > 16 000 clinical samples for H1N1/2009. Most were from patients clinically diagnosed with H1N1/2009. Out of these, 9% were positive. This study sought to determine what respiratory pathogens were misdiagnosed as cases of H1N1/2009 during this time. METHODS: We examined the results from 3247 samples which were sent to the laboratory during April-July 2009. All were from patients clinically diagnosed as having H1N1/2009 (based on accepted criteria) and all were given a full respiratory screen using real time reverse transcriptase polymerase chain reaction (rtRT-PCR) assays. RESULTS: In total, respiratory pathogens were detected in 27.9% (95% confidence interval, 26.3-29.5%) of the samples submitted. Numerous pathogens were detected, the most common of which were rhinovirus (8.9% (95% confidence interval, 7.9-9.9%)), parainfluenza 1 (1.9% (95% confidence interval, 1.4-2.4%)) and 3 (4.1% (95% confidence interval, 3.3-4.9%)), and adenovirus ((3.5% (95% confidence interval, 2.9-4.2%)). CONCLUSIONS: This study highlights the problems of using a clinical algorithm to detect H1N1/2009. Clinicians frequently misdiagnosed common respiratory pathogens as H1N1/2009 during the spring/summer outbreak in Scotland. Many undesirable consequences would have resulted, relating to treatment, infection control, and public health surveillance.",2011 Jul 13,"['Gunson, Rory N', 'Carman, William F']",BMC Infect Dis,,,True
d9006d571ae04afb914b4bdd5c32f2090d409b4c,PMC,Agent-based simulation for weekend-extension strategies to mitigate influenza outbreaks,http://dx.doi.org/10.1186/1471-2458-11-522,PMC3146865,21718518,CC BY,"BACKGROUND: Non-pharmaceutical strategies are vital in curtailing impacts of influenza and have been intensively studied in public health. However, few strategies have explicitly utilized the weekend effect, which has been widely reported to be capable of reducing influenza infections. This study aims to explore six weekend-extension strategies against seasonal and pandemic flu outbreaks. METHODS: The weekend-extension strategies were designed to extend regular two-day weekend by one, two and three days, respectively, and in combination with either a continuous or discontinuous pattern. Their effectiveness was evaluated using an established agent-based spatially explicit simulation model in the urbanized area of Buffalo, NY, US. RESULTS: If the extensions last more than two days, the weekend-extension strategies can remarkably reduce the overall disease attack rate of seasonal flu. Particularly, a three-day continuous extension is sufficient to suppress the epidemic and confine the spread of disease. For the pandemic flu, the weekend-extension strategies only produce a few mitigation effects until the extensions exceed three days. Sensitivity analysis indicated that a compliance level above 75% is necessary for the weekend-extension strategies to take effects. CONCLUSION: This research is the first attempt to incorporate the weekend effect into influenza mitigation strategies. The results suggest that appropriate extensions of the regular two-day weekend can be a potential measure to fight against influenza outbreaks, while minimizing interruptions on normal rhythms of socio-economy. The concept of weekend extension would be particularly useful if there were a lack of vaccine stockpiles, e.g., in countries with limited health resources, or in the case of unknown emerging infectious diseases.",2011 Jun 30,"Mao, Liang",BMC Public Health,,,True
47fb645312a069e65bb7557c58204244c3c92953,PMC,Immunoproteomic analysis of bacterial proteins of Actinobacillus pleuropneumoniae serotype 1,http://dx.doi.org/10.1186/1477-5956-9-32,PMC3148531,21703014,CC BY,"BACKGROUND: Actinobacillus pleuropneumoniae (APP) is one of the most important swine pathogens worldwide. Identification and characterization of novel antigenic APP vaccine candidates are underway. In the present study, we use an immunoproteomic approach to identify APP protein antigens that may elicit an immune response in serotype 1 naturally infected swine and serotype 1 virulent strain S259-immunized rabbits. RESULTS: Proteins from total cell lysates of serotype 1 APP were separated by two-dimensional electrophoresis (2DE). Western blot analysis revealed 21 immunoreactive protein spots separated in the pH 4-7 range and 4 spots in the pH 7-11 range with the convalescent sera from swine; we found 5 immunoreactive protein spots that separated in the pH 4-7 range and 2 in the pH 7-11 range with hyperimmune sera from S259-immunized rabbits. The proteins included the known antigens ApxIIA, protective surface antigen D15, outer membrane proteins P5, subunit NqrA. The remaining antigens are being reported as immunoreactive proteins in APP for the first time, to our knowledge. CONCLUSIONS: We identified a total of 42 immunoreactive proteins of the APP serotype 1 virulent strain S259 which represented 32 different proteins, including some novel immunoreactive factors which could be researched as vaccine candidates.",2011 Jun 26,"['Zhang, Wei', 'Shao, Jing', 'Liu, Guangjin', 'Tang, Fang', 'Lu, Yan', 'Zhai, Zhipeng', 'Wang, Yang', 'Wu, Zongfu', 'Yao, Huochun', 'Lu, Chengping']",Proteome Sci,,,True
a730b4d5a5a0353503a1cd46d458635f93618805,PMC,Compare the differences of synonymous codon usage between the two species within cardiovirus,http://dx.doi.org/10.1186/1743-422X-8-325,PMC3148564,21708006,CC BY,"BACKGROUND: Cardioviruses are positive-strand RNA viruses in the Picornaviridae family that can cause enteric infection in rodents and also been detected at lower frequencies in other mammals such as pigs and human beings. The Cardiovirus genus consists two distinct species: Encephalomyocarditis virus (EMCV) and Theilovirus (ThV). There are a lot differences between the two species. In this study, the differences of codon usage in EMCV and ThV were compared. RESULTS: The mean ENC values of EMCV and ThV are 54.86 and 51.08 respectively, higher than 40.And there are correlations between (C+G)(12)% and (C+G)(3)% for both EMCV and ThV (r = -0.736;r = 0.986, P < 0.01, repectively). For ThV the (C+G)(12)%, (C+G)(3)%, axis f'(1 )and axis f'(2 )had a significant correlations respectively but not for EMCV. According to the RSCU values, the EMCV species seemed to prefer U, G and C ending codon, while the ThV spice seemed to like using U and A ending codon. However, in both genus AGA for Arg, AUU for Ile, UCU for Ser, and GGA for Gly were chosen preferentially. Correspondence analysis detected one major trend in the first axis (f'(1)) which accounted for 22.89% of the total variation, and another major trend in the second axis (f'(2)) which accounted for 17.64% of the total variation. And the plots of the same serotype seemed at the same region at the coordinate. CONCLUSION: The overall extents of codon usage bias in both EMCV and ThV are low. The mutational pressure is the main factor that determines the codon usage bias, but the (C+G) content plays a more important role in codon usage bias for ThV than for EMCV. The synonymous codon usage pattern in both EMCV and ThV genes is gene function and geography specific, but not host specific. Maybe the serotype is one factor effected the codon bias for ThV, and location has no significant effect on the variations of synonymous codon usage in these virus genes.",2011 Jun 27,"['Liu, Wen-qian', 'Zhang, Jie', 'Zhang, Yi-qiang', 'Zhou, Jian-hua', 'Chen, Hao-tai', 'Ma, Li-na', 'Ding, Yao-zhong', 'Liu, Yongsheng']",Virol J,,,True
121638b718d18f7bb5086223540f74cf61e49800,PMC,Severe community-acquired adenovirus pneumonia in an immunocompetent 44-year-old woman: a case report and review of the literature,http://dx.doi.org/10.1186/1752-1947-5-259,PMC3148995,21718493,CC BY,"INTRODUCTION: This case report describes a rare condition: community-acquired adenovirus pneumonia in an immunocompetent adult. The diagnosis was achieved by using a multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay and highlights the usefulness of these novel molecular diagnostic techniques in patients hospitalized with acute respiratory illness. We also performed a literature search for previously published cases and present a summary of the clinical, laboratory and radiological features of this condition. CASE PRESENTATION: A 44-year-old immunocompetent Caucasian woman was admitted to our hospital with an acute febrile respiratory illness associated with a rash. Her blood tests were non-specifically abnormal, and tests for bacterial pathogens were negative. Her condition rapidly deteriorated while she was in our hospital and required mechanical ventilation and inotropic support. A multiplex real-time RT-PCR assay performed on respiratory specimens to detect respiratory viruses was negative for influenza but positive for adenovirus DNA. The patient recovered on supportive treatment, and antibiotics were stopped after 5 days. CONCLUSIONS: Community-acquired adenovirus pneumonia in immunocompetent adult civilians presents as a non-specific acute febrile respiratory illness followed by the abrupt onset of respiratory failure, often requiring mechanical ventilation. Its laboratory and radiological features are typical of viral infections but also are non-specific. Novel multiplex real-time RT-PCR testing for respiratory viruses enabled us to rapidly make the diagnosis in this case. The new technology could be used more widely in patients with acute respiratory illness and has potential utility for rationalization of the use of antibiotics and improving infection control measures.",2011 Jun 30,"['Clark, Tristan W', 'Fleet, Daniel H', 'Wiselka, Martin J']",J Med Case Reports,,,True
7120211f7eda128e441ed22e3e4d8d3eda07b771,PMC,Effect of oral care gel on the quality of life for oral lichen planus in patients with chronic HCV infection,http://dx.doi.org/10.1186/1743-422X-8-348,PMC3149004,21749712,CC BY,"BACKGROUND: Oral lichen planus (OLP) decreases the quality of life because it can cause spontaneous pain during eating and tooth-brushing and an uncomfortable feeling in the mouth. In addition, OLP may be associated with HCV-related liver disease. We investigated the visual analogue scale (VAS) and effects of oral care gel, REFRECARE-H(®), on patients with OLP associated with HCV infection. RESULTS: Nine OLP patients (mean age 67.9 ± 7.6 years) with HCV-related liver diseases were recruited and their VAS score determined along with a biochemical examination of the blood. Types of OLP included erosive (6 patients) and reticular (3). REFRECARE-H(®), an oral care gel (therapeutic dentifrice) containing hinokitiol, was applied by each patient as a thin layer on the oral membrane, after each meal and at bedtime for 30 days. Application of REFRECARE-H(® )improved the quality of life in all terms of dry mouth, breath odor, oral freshness, oral pain during rest, oral pain at a mealtimes, taste disorder, loss of appetite, sleep disorder, depressive mood and jitteriness. VAS scores of dry mouth, breath odor, oral freshness, and sleep disorder were significantly increased 30 days after application of REFRECARE-H(® )(P = 0.01, P = 0.05, P = 0.03, P = 0.04). VAS scores of oral pain at a mealtimes and taste disorder were increased 30 days after application of REFRECARE-H(® )(P = 0.06). There was an absence of side effects. CONCLUSIONS: REFRECARE-H(® )improved the quality of life for OLP. It is necessary for the hepatologist to educate patients regarding oral hygiene, as well as provide treatment of liver disease.",2011 Jul 12,"['Nagao, Yumiko', 'Sata, Michio']",Virol J,,,True
24e8a04adeb7f1142768d4de1e10d8ac48afcd03,PMC,Investigation of Griffithsin's Interactions with Human Cells Confirms Its Outstanding Safety and Efficacy Profile as a Microbicide Candidate,http://dx.doi.org/10.1371/journal.pone.0022635,PMC3149051,21829638,CC0,"Many natural product-derived lectins such as the red algal lectin griffithsin (GRFT) have potent in vitro activity against viruses that display dense clusters of oligomannose N-linked glycans (NLG) on their surface envelope glycoproteins. However, since oligomannose NLG are also found on some host proteins it is possible that treatment with antiviral lectins may trigger undesirable side effects. For other antiviral lectins such as concanavalin A, banana lectin and cyanovirin-N (CV-N), interactions between the lectin and as yet undescribed cellular moieties have been reported to induce undesirable side effects including secretion of inflammatory cytokines and activation of host T-cells. We show that GRFT, unlike CV-N, binds the surface of human epithelial and peripheral blood mononuclear cells (PBMC) through an exclusively oligosaccharide-dependent interaction. In contrast to several other antiviral lectins however, GRFT treatment induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells or human PBMC, has no measureable effect on cell viability and does not significantly upregulate markers of T-cell activation. In addition, GRFT appears to retain antiviral activity once bound to the surface of PBMC. Finally, RNA microarray studies show that, while CV-N and ConA regulate expression of a multitude of cellular genes, GRFT treatment effects only minimal alterations in the gene expression profile of a human ectocervical cell line. These studies indicate that GRFT has an outstanding safety profile with little evidence of induced toxicity, T-cell activation or deleterious immunological consequence, unique attributes for a natural product-derived lectin.",2011 Aug 2,"['Kouokam, Joseph Calvin', 'Huskens, Dana', 'Schols, Dominique', 'Johannemann, Andrew', 'Riedell, Shonna K.', 'Walter, Wendye', 'Walker, Janice M.', 'Matoba, Nobuyuki', ""O'Keefe, Barry R."", 'Palmer, Kenneth E.']",PLoS One,,,True
06589343cb2fcc62a39c587071c8a9e76836f993,PMC,Analysis of CDC social control measures using an agent-based simulation of an influenza epidemic in a city,http://dx.doi.org/10.1186/1471-2334-11-199,PMC3151229,21767379,CC BY,"BACKGROUND: The transmission of infectious disease amongst the human population is a complex process which requires advanced, often individual-based, models to capture the space-time details observed in reality. METHODS: An Individual Space-Time Activity-based Model (ISTAM) was applied to simulate the effectiveness of non-pharmaceutical control measures including: (1) refraining from social activities, (2) school closure and (3) household quarantine, for a hypothetical influenza outbreak in an urban area. RESULTS: Amongst the set of control measures tested, refraining from social activities with various compliance levels was relatively ineffective. Household quarantine was very effective, especially for the peak number of cases and total number of cases, with large differences between compliance levels. Household quarantine resulted in a decrease in the peak number of cases from more than 300 to around 158 for a 100% compliance level, a decrease of about 48.7%. The delay in the outbreak peak was about 3 to 17 days. The total number of cases decreased to a range of 3635-5403, that is, 63.7%-94.7% of the baseline value. When coupling control measures, household quarantine together with school closure was the most effective strategy. The resulting space-time distribution of infection in different classes of activity bundles (AB) suggests that the epidemic outbreak is strengthened amongst children and then spread to adults. By sensitivity analysis, this study demonstrated that earlier implementation of control measures leads to greater efficacy. Also, for infectious diseases with larger basic reproduction number, the effectiveness of non-pharmaceutical measures was shown to be limited. CONCLUSIONS: Simulated results showed that household quarantine was the most effective control measure, while school closure and household quarantine implemented together achieved the greatest benefit. Agent-based models should be applied in the future to evaluate the efficacy of control measures for a range of disease outbreaks in a range of settings given sufficient information about the given case and knowledge about the transmission processes at a fine scale.",2011 Jul 18,"['Yang, Yong', 'Atkinson, Peter M', 'Ettema, Dick']",BMC Infect Dis,,,True
4a0df4a0f4d88046442f66ad84ba40b2c34e2493,PMC,The Interaction of LFA-1 on Mononuclear Cells and ICAM-1 on Tubular Epithelial Cells Accelerates TGF-β1-Induced Renal Epithelial-Mesenchymal Transition,http://dx.doi.org/10.1371/journal.pone.0023267,PMC3151298,21850266,CC BY,"The epithelial-mesenchymal transition (EMT) of renal epithelial cells (RTECs) has pivotal roles in the development of renal fibrosis. Although the interaction of lymphocyte function-associated antigen 1 (LFA-1) on leukocytes and its ligand, intracellular adhesion molecule 1 (ICAM-1), plays essential roles in most inflammatory reactions, its pathogenetic role in the EMT of RTECs remains to be clarified. In the present study, we investigated the effect of the interaction of LFA-1 on peripheral blood mononuclear cells (PBMCs) and ICAM-1 on HK-2 cells after stimulation with TGF-β(1) on the EMT of RTECs. ICAM-1 was highly expressed in HK-2 cells. After TGF-β(1) stimulation, the chemokines CCL3 and CXCL12 increased on HK-2 cells. After co-culture of PBMCs and HK-2 cells pre-stimulated with TGF-β(1) (0.1 ng/ml) (HK-2-TGF-β(1) (0.1)), the expression of the active form of LFA-1 increased on PBMCs; however, total LFA-1 expression did not change. The expression of the active form of LFA-1 on PBMCs did not increase after co-culture with not CCL3 but CXCL12 knockdown HK-2-TGF-β(1) (0.1). The expression of epithelial cell junction markers (E-cadherin and occludin) further decreased and that of mesenchymal markers (vimentin and fibronectin) further increased in HK-2-TGF-β(1) (0.1) after co-culture with PBMCs for 24 hrs (HK-2-TGF-β(1) (0.1)-PBMCs). The phosphorylation of ERK 1/2 but not smad2 and smad3 increased in HK-2-TGF-β(1) (0.1)-PBMCs. The snail and slug signaling did not increase HK-2-TGF-β(1) (0.1)-PBMCs. Although the migration and invasion of HK-2 cells induced full EMT by a high dose (10.0 ng/ml) and long-term (72–96 hrs) TGF-β(1) stimulation increased, that of HK-2-TGF-β(1) (0.1)-PBMCs did not increase. These results suggested that HK-2 cells stimulated with TGF-β(1) induced conformational activation of LFA-1 on PBMCs by increased CXCL12. Then, the direct interaction of LFA-1 on PBMCs and ICAM-1 on HK-2 cells activated ERK1/2 signaling to accelerate the part of EMT of HK-2 cells induced by TGF-β(1.)",2011 Aug 5,"['Morishita, Yoshiyuki', 'Watanabe, Minami', 'Nakazawa, Eiko', 'Ishibashi, Kenichi', 'Kusano, Eiji']",PLoS One,,,True
b87dbfb99e667d88cda4e153340b44404f7b4c98,PMC,Entry screening to delay local transmission of 2009 pandemic influenza A (H1N1),http://dx.doi.org/10.1186/1471-2334-10-82,PMC3152767,20353566,CC BY,"BACKGROUND: After the WHO issued the global alert for 2009 pandemic influenza A (H1N1), many national health agencies began to screen travelers on entry in airports, ports and border crossings to try to delay local transmission. METHODS: We reviewed entry screening policies adopted by different nations and ascertained dates of official report of the first laboratory-confirmed imported H1N1 case and the first laboratory-confirmed untraceable or 'local' H1N1 case. RESULTS: Implementation of entry screening policies was associated with on average additional 7-12 day delays in local transmission compared to nations that did not implement entry screening, with lower bounds of 95% confidence intervals consistent with no additional delays and upper bounds extending to 20-30 day additional delays. CONCLUSIONS: Entry screening may lead to short-term delays in local transmission of a novel strain of influenza virus. The resources required for implementation should be balanced against the expected benefits of entry screening.",2010 Mar 30,"['Cowling, Benjamin J', 'Lau, Lincoln LH', 'Wu, Peng', 'Wong, Helen WC', 'Fang, Vicky J', 'Riley, Steven', 'Nishiura, Hiroshi']",BMC Infect Dis,,,True
1ec08de8b92b3b6c9be98dcd92db0ddf3efdad44,PMC,Immunomodulator expression in trophoblasts from the feline immunodeficiency virus (FIV)-infected cat,http://dx.doi.org/10.1186/1743-422X-8-336,PMC3152912,21729293,CC BY,"BACKGROUND: FIV infection frequently compromises pregnancy under experimental conditions and is accompanied by aberrant expression of some placental cytokines. Trophoblasts produce numerous immunomodulators that play a role in placental development and pregnancy maintenance. We hypothesized that FIV infection may cause dysregulation of trophoblast immunomodulator expression, and aberrant expression of these molecules may potentiate inflammation and compromise pregnancy. The purpose of this project was to evaluate the expression of representative pro-(TNF-α, IFN-γ, IL-1β, IL-2, IL-6, IL-12p35, IL-12p40, IL-18, and GM-CSF) and anti-inflammatory cytokines (IL-4, IL-5, and IL-10); CD134, a secondary co-stimulatory molecule expressed on activated T cells (FIV primary receptor); the chemokine receptor CXCR4 (FIV co-receptor); SDF-1α, the chemokine ligand to CXCR4; and FIV gag in trophoblasts from early-and late-term pregnancy. METHODS: We used an anti-cytokeratin antibody in immunohistochemistry to identify trophoblasts selectively, collected these cells using laser capture microdissection, and extracted total RNA from the captured cell populations. Real time, reverse transcription-PCR was used to quantify gene expression. RESULTS: We detected IL-4, IL-5, IL-6, IL-1β, IL-12p35, IL-12p40, and CXCR4 in trophoblasts from early-and late-term pregnancy. Expression of cytokines increased from early to late pregnancy in normal tissues. A clear, pro-inflammatory microenvironment was not evident in trophoblasts from FIV-infected queens at either stage of pregnancy. Reproductive failure was accompanied by down-regulation of both pro-and anti-inflammatory cytokines. CD134 was not detected in trophoblasts, and FIV gag was detected in only one of ten trophoblast specimens collected from FIV-infected queens. CONCLUSION: Feline trophoblasts express an array of pro-and anti-inflammatory immunomodulators whose expression increases from early to late pregnancy in normal tissues. Non-viable pregnancies were associated with decreased expression of immunomodulators which regulate trophoblast invasion in other species. The detection of FIV RNA in trophoblasts was rare, suggesting that the high rate of reproductive failure in FIV-infected queens was not a direct result of viral replication in trophoblasts. The influence of placental immune cells on trophoblast function and pregnancy maintenance in the FIV-infected cat requires additional study.",2011 Jul 5,"['Scott, Veronica L', 'Shack, Leslie A', 'Eells, Jeffrey B', 'Ryan, Peter L', 'Donaldson, Janet R', 'Coats, Karen S']",Virol J,,,True
6224ce8bb65afbb10b08238d5ecde8991d7ab0e2,PMC,Toxin-Based Therapeutic Approaches,http://dx.doi.org/10.3390/toxins2112519,PMC3153180,22069564,CC BY,"Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin.",2010 Oct 28,"['Shapira, Assaf', 'Benhar, Itai']",Toxins (Basel),,,True
eaf46f27d9c28f8b3c818b0d7969d9188a7e9c11,PMC,RNA-Binding Domain in the Nucleocapsid Protein of Gill-Associated Nidovirus of Penaeid Shrimp,http://dx.doi.org/10.1371/journal.pone.0022156,PMC3153931,21857914,CC BY,"Gill-associated virus (GAV) infects Penaeus monodon shrimp and is the type species okavirus in the Roniviridae, the only invertebrate nidoviruses known currently. Electrophoretic mobility shift assays (EMSAs) using His(6)-tagged full-length and truncated proteins were employed to examine the nucleic acid binding properties of the GAV nucleocapsid (N) protein in vitro. The EMSAs showed full-length N protein to bind to all synthetic single-stranded (ss)RNAs tested independent of their sequence. The ssRNAs included (+) and (−) sense regions of the GAV genome as well as a (+) sense region of the M RNA segment of Mourilyan virus, a crustacean bunya-like virus. GAV N protein also bound to double-stranded (ds)RNAs prepared to GAV ORF1b gene regions and to bacteriophage M13 genomic ssDNA. EMSAs using the five N protein constructs with variable-length N-terminal and/or C-terminal truncations localized the RNA binding domain to a 50 amino acid (aa) N-terminal sequence spanning Met(11) to Arg(60). Similarly to other RNA binding proteins, the first 16 aa portion of this sequence was proline/arginine rich. To examine this domain in more detail, the 18 aa peptide (M(11)PVRRPLPPQPPRNARLI(29)) encompassing this sequence was synthesized and found to bind nucleic acids similarly to the full-length N protein in EMSAs. The data indicate a fundamental role for the GAV N protein proline/arginine-rich domain in nucleating genomic ssRNA to form nucleocapsids. Moreover, as the synthetic peptide formed higher-order complexes in the presence of RNA, the domain might also play some role in protein/protein interactions stabilizing the helical structure of GAV nucleocapsids.",2011 Aug 3,"['Soowannayan, Chumporn', 'Cowley, Jeff A.', 'Michalski, Wojtek P.', 'Walker, Peter J.']",PLoS One,,,True
0a0cbd4cb08c862deadcb5aaef22a27b770c0791,PMC,Real-world comparison of two molecular methods for detection of respiratory viruses,http://dx.doi.org/10.1186/1743-422X-8-332,PMC3154182,21714915,CC BY,"BACKGROUND: Molecular polymerase chain reaction (PCR) based assays are increasingly used to diagnose viral respiratory infections and conduct epidemiology studies. Molecular assays have generally been evaluated by comparing them to conventional direct fluorescent antibody (DFA) or viral culture techniques, with few published direct comparisons between molecular methods or between institutions. We sought to perform a real-world comparison of two molecular respiratory viral diagnostic methods between two experienced respiratory virus research laboratories. METHODS: We tested nasal and throat swab specimens obtained from 225 infants with respiratory illness for 11 common respiratory viruses using both a multiplex assay (Respiratory MultiCode-PLx Assay [RMA]) and individual real-time RT-PCR (RT-rtPCR). RESULTS: Both assays detected viruses in more than 70% of specimens, but there was discordance. The RMA assay detected significantly more human metapneumovirus (HMPV) and respiratory syncytial virus (RSV), while RT-rtPCR detected significantly more influenza A. We speculated that primer differences accounted for these discrepancies and redesigned the primers and probes for influenza A in the RMA assay, and for HMPV and RSV in the RT-rtPCR assay. The tests were then repeated and again compared. The new primers led to improved detection of HMPV and RSV by RT-rtPCR assay, but the RMA assay remained similar in terms of influenza detection. CONCLUSIONS: Given the absence of a gold standard, clinical and research laboratories should regularly correlate the results of molecular assays with other PCR based assays, other laboratories, and with standard virologic methods to ensure consistency and accuracy.",2011 Jun 29,"['Ali, S Asad', 'Gern, James E', 'Hartert, Tina V', 'Edwards, Kathryn M', 'Griffin, Marie R', 'Miller, E Kathryn', 'Gebretsadik, Tebeb', 'Pappas, Tressa', 'Lee, Wai- ming', 'Williams, John V']",Virol J,,,True
ce7b8f00255cb989194bd19a730abd529c0d1f82,PMC,The Microbial Detection Array Combined with Random Phi29-Amplification Used as a Diagnostic Tool for Virus Detection in Clinical Samples,http://dx.doi.org/10.1371/journal.pone.0022631,PMC3154197,21853040,CC BY,"A common technique used for sensitive and specific diagnostic virus detection in clinical samples is PCR that can identify one or several viruses in one assay. However, a diagnostic microarray containing probes for all human pathogens could replace hundreds of individual PCR-reactions and remove the need for a clear clinical hypothesis regarding a suspected pathogen. We have established such a diagnostic platform for random amplification and subsequent microarray identification of viral pathogens in clinical samples. We show that Phi29 polymerase-amplification of a diverse set of clinical samples generates enough viral material for successful identification by the Microbial Detection Array, demonstrating the potential of the microarray technique for broad-spectrum pathogen detection. We conclude that this method detects both DNA and RNA virus, present in the same sample, as well as differentiates between different virus subtypes. We propose this assay for diagnostic analysis of viruses in clinical samples.",2011 Aug 10,"['Erlandsson, Lena', 'Rosenstierne, Maiken W.', 'McLoughlin, Kevin', 'Jaing, Crystal', 'Fomsgaard, Anders']",PLoS One,,,True
98948855a76926474a0ca576cf984b00053fcac3,PMC,B Cell Repertoire Analysis Identifies New Antigenic Domains on Glycoprotein B of Human Cytomegalovirus which Are Target of Neutralizing Antibodies,http://dx.doi.org/10.1371/journal.ppat.1002172,PMC3154849,21852946,CC BY,"Human cytomegalovirus (HCMV), a herpesvirus, is a ubiquitously distributed pathogen that causes severe disease in immunosuppressed patients and infected newborns. Efforts are underway to prepare effective subunit vaccines and therapies including antiviral antibodies. However, current vaccine efforts are hampered by the lack of information on protective immune responses against HCMV. Characterizing the B-cell response in healthy infected individuals could aid in the design of optimal vaccines and therapeutic antibodies. To address this problem, we determined, for the first time, the B-cell repertoire against glycoprotein B (gB) of HCMV in different healthy HCMV seropositive individuals in an unbiased fashion. HCMV gB represents a dominant viral antigenic determinant for induction of neutralizing antibodies during infection and is also a component in several experimental HCMV vaccines currently being tested in humans. Our findings have revealed that the vast majority (>90%) of gB-specific antibodies secreted from B-cell clones do not have virus neutralizing activity. Most neutralizing antibodies were found to bind to epitopes not located within the previously characterized antigenic domains (AD) of gB. To map the target structures of these neutralizing antibodies, we generated a 3D model of HCMV gB and used it to identify surface exposed protein domains. Two protein domains were found to be targeted by the majority of neutralizing antibodies. Domain I, located between amino acids (aa) 133–343 of gB and domain II, a discontinuous domain, built from residues 121–132 and 344–438. Analysis of a larger panel of human sera from HCMV seropositive individuals revealed positivity rates of >50% against domain I and >90% against domain II, respectively. In accordance with previous nomenclature the domains were designated AD-4 (Dom II) and AD-5 (Dom I), respectively. Collectively, these data will contribute to optimal vaccine design and development of antibodies effective in passive immunization.",2011 Aug 11,"['Pötzsch, Sonja', 'Spindler, Nadja', 'Wiegers, Anna-Katharina', 'Fisch, Tanja', 'Rücker, Pia', 'Sticht, Heinrich', 'Grieb, Nina', 'Baroti, Tina', 'Weisel, Florian', 'Stamminger, Thomas', 'Martin-Parras, Luis', 'Mach, Michael', 'Winkler, Thomas H.']",PLoS Pathog,,,True
27b920651fc5c0ed145e70d1ab314ca3efc70754,PMC,B Cell Repertoire Analysis Identifies New Antigenic Domains on Glycoprotein B of Human Cytomegalovirus which Are Target of Neutralizing Antibodies,http://dx.doi.org/10.1371/journal.ppat.1002172,PMC3154849,21852946,CC BY,"Human cytomegalovirus (HCMV), a herpesvirus, is a ubiquitously distributed pathogen that causes severe disease in immunosuppressed patients and infected newborns. Efforts are underway to prepare effective subunit vaccines and therapies including antiviral antibodies. However, current vaccine efforts are hampered by the lack of information on protective immune responses against HCMV. Characterizing the B-cell response in healthy infected individuals could aid in the design of optimal vaccines and therapeutic antibodies. To address this problem, we determined, for the first time, the B-cell repertoire against glycoprotein B (gB) of HCMV in different healthy HCMV seropositive individuals in an unbiased fashion. HCMV gB represents a dominant viral antigenic determinant for induction of neutralizing antibodies during infection and is also a component in several experimental HCMV vaccines currently being tested in humans. Our findings have revealed that the vast majority (>90%) of gB-specific antibodies secreted from B-cell clones do not have virus neutralizing activity. Most neutralizing antibodies were found to bind to epitopes not located within the previously characterized antigenic domains (AD) of gB. To map the target structures of these neutralizing antibodies, we generated a 3D model of HCMV gB and used it to identify surface exposed protein domains. Two protein domains were found to be targeted by the majority of neutralizing antibodies. Domain I, located between amino acids (aa) 133–343 of gB and domain II, a discontinuous domain, built from residues 121–132 and 344–438. Analysis of a larger panel of human sera from HCMV seropositive individuals revealed positivity rates of >50% against domain I and >90% against domain II, respectively. In accordance with previous nomenclature the domains were designated AD-4 (Dom II) and AD-5 (Dom I), respectively. Collectively, these data will contribute to optimal vaccine design and development of antibodies effective in passive immunization.",2011 Aug 11,"['Pötzsch, Sonja', 'Spindler, Nadja', 'Wiegers, Anna-Katharina', 'Fisch, Tanja', 'Rücker, Pia', 'Sticht, Heinrich', 'Grieb, Nina', 'Baroti, Tina', 'Weisel, Florian', 'Stamminger, Thomas', 'Martin-Parras, Luis', 'Mach, Michael', 'Winkler, Thomas H.']",PLoS Pathog,,,False
72f81539c6237420551180793d727062bdd043bd,PMC,Successful Control of Methicillin-Resistant Staphylococcus aureus in Endemic Neonatal Intensive Care Units—A 7-Year Campaign,http://dx.doi.org/10.1371/journal.pone.0023001,PMC3155524,21857979,CC BY,"BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is among the most important nosocomial pathogens in the intensive care unit (ICU) worldwide, including Taiwan. Since 1997, our neonatal ICUs (NICUs) had become endemic for MRSA. METHODOLOGY/PRINCIPAL FINDINGS: To control MRSA spread in our NICUs, we implemented a series of infection control measures stepwise, including reinforcement of hand hygiene since January 2000, augmentation of aseptic care over the insertion site of central venous catheter since July 2001, introduction of alcohol-based handrubs since April 2003, surveillance culture for MRSA and cohort care for the colonized patients between March 2003 and February 2004, and surveillance culture with subsequent decolonization of MRSA between August 2005 and July 2006. After implementation of these measures, MRSA healthcare-associated infection (HAI) density reduced by 92%, from 5.47 episodes per 1000 patient-days in 1999 to 0.45 episodes per 1000 patient-days in 2006; MRSA bloodstream infection reduced from 40 cases in 1999 to only one case in 2006. Compared to those obtained during the period of surveillance culture without decolonization, both rates of MRSA colonization (8.6% vs. 41%, p<0.001) and infection (1.1% vs. 12%, p<0.001) decreased significantly during the period of surveillance and decolonization. Molecular analysis of the clinical isolates during the study period showed that the endemic clone, which dominated between 1998 and 2005, almost disappeared in 2006, while the community clones increased significantly in 2006–2007. CONCLUSION/SIGNIFICANCE: Through infection control measures, MRSA HAIs can be successfully controlled, even in areas with high levels of endemic MRSA infections such as our NICUs.",2011 Aug 12,"['Huang, Yhu-Chering', 'Lien, Rey-In', 'Su, Lin-Hui', 'Chou, Yi-Hong', 'Lin, Tzou-Yien']",PLoS One,,,True
87dda3063b97a87338264b45ae16045e46cb237b,PMC,Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity,http://dx.doi.org/10.1371/journal.pntd.0001279,PMC3156690,21858242,CC BY,"The Chikungunya virus infection zones have now quickly spread from Africa to parts of Asia, North America and Europe. Originally thought to trigger a disease of only mild symptoms, recently Chikungunya virus caused large-scale fatalities and widespread economic loss that was linked to recent virus genetic mutation and evolution. Due to the paucity of information on Chikungunya immunological progression, we investigated the serum levels of 13 cytokines/chemokines during the acute phase of Chikungunya disease and 6- and 12-month post-infection follow-up from patients of the Italian outbreak. We found that CXCL9/MIG, CCL2/MCP-1, IL-6 and CXCL10/IP-10 were significantly raised in the acute phase compared to follow-up samples. Furthermore, IL-1β, TNF-α, Il-12, IL-10, IFN-γ and IL-5 had low initial acute phase levels that significantly increased at later time points. Analysis of symptom severity showed association with CXCL9/MIG, CXCL10/IP-10 and IgG levels. These data give insight into Chikungunya disease establishment and subsequent convalescence, which is imperative to the treatment and containment of this quickly evolving and frequently re-emerging disease.",2011 Aug 16,"['Kelvin, Alyson A.', 'Banner, David', 'Silvi, Giuliano', 'Moro, Maria Luisa', 'Spataro, Nadir', 'Gaibani, Paolo', 'Cavrini, Francesca', 'Pierro, Anna', 'Rossini, Giada', 'Cameron, Mark J.', 'Bermejo-Martin, Jesus F.', 'Paquette, Stéphane G.', 'Xu, Luoling', 'Danesh, Ali', 'Farooqui, Amber', 'Borghetto, Ilaria', 'Kelvin, David J.', 'Sambri, Vittorio', 'Rubino, Salvatore']",PLoS Negl Trop Dis,,,True
64bfeb561f0664d74a04ee30a24a48159261d4fd,PMC,The Failure of R (0),http://dx.doi.org/10.1155/2011/527610,PMC3157160,21860658,CC BY,"The basic reproductive ratio, R (0), is one of the fundamental concepts in mathematical biology. It is a threshold parameter, intended to quantify the spread of disease by estimating the average number of secondary infections in a wholly susceptible population, giving an indication of the invasion strength of an epidemic: if R (0) < 1, the disease dies out, whereas if R (0) > 1, the disease persists. R (0) has been widely used as a measure of disease strength to estimate the effectiveness of control measures and to form the backbone of disease-management policy. However, in almost every aspect that matters, R (0) is flawed. Diseases can persist with R (0) < 1, while diseases with R (0) > 1 can die out. We show that the same model of malaria gives many different values of R (0), depending on the method used, with the sole common property that they have a threshold at 1. We also survey estimated values of R (0) for a variety of diseases, and examine some of the alternatives that have been proposed. If R (0) is to be used, it must be accompanied by caveats about the method of calculation, underlying model assumptions and evidence that it is actually a threshold. Otherwise, the concept is meaningless.",2011 Aug 16,"['Li, Jing', 'Blakeley, Daniel', 'Smith?, Robert J.']",Comput Math Methods Med,,,True
f4c1afe385e9e31eb5678e15a3c280ba97326554,PMC,High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France,http://dx.doi.org/10.1371/journal.pone.0023514,PMC3157400,21858150,CC BY,"BACKGROUND: Influenza-like illness (ILI) may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. OBJECTIVES: During the early weeks of the 2009–2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. METHODS: H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5%) were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9%) were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%), followed by parainfluenza viruses (24.2%) and adenovirus (5.3%). 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. CONCLUSION: Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management.",2011 Aug 17,"['Schnepf, Nathalie', 'Resche-Rigon, Matthieu', 'Chaillon, Antoine', 'Scemla, Anne', 'Gras, Guillaume', 'Semoun, Oren', 'Taboulet, Pierre', 'Molina, Jean-Michel', 'Simon, François', 'Goudeau, Alain', 'LeGoff, Jérôme']",PLoS One,,,True
7ba2b38fdd8158bce40520cb0a93c1d2889f64f9,PMC,Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus,http://dx.doi.org/10.1371/journal.pone.0023374,PMC3158760,21886787,CC BY,"Subtype specificity of influenza A virus (IAV) is determined by its two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). For HA, 16 distinct subtypes (H1–H16) exist, while nine exist for NA. The epidemic strains of H1N1 IAV change frequently and cause annual seasonal epidemics as well as occasional pandemics, such as the notorious 1918 influenza pandemic. The recent introduction of pandemic A/H1N1 IAV (H1N1pdm virus) into humans re-emphasizes the public health concern about H1N1 IAV. Several studies have identified conserved epitopes within specific HA subtypes that can be used for diagnostics. However, immune specific epitopes in H1N1 IAV have not been completely assessed. In this study, linear epitopes on the H1N1pdm viral HA protein were identified by peptide scanning using libraries of overlapping peptides against convalescent sera from H1N1pdm patients. One epitope, P5 (aa 58–72) was found to be immunodominant in patients and to evoke high titer antibodies in mice. Multiple sequence alignments and in silico coverage analysis showed that this epitope is highly conserved in influenza H1 HA [with a coverage of 91.6% (9,860/10,767)] and almost completely absent in other subtypes [with a coverage of 3.3% (792/23,895)]. This previously unidentified linear epitope is located outside the five well-recognized antigenic sites in HA. A peptide ELISA method based on this epitope was developed and showed high correlation (χ(2) = 51.81, P<0.01, Pearson correlation coefficient R = 0.741) with a hemagglutination inhibition test. The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs.",2011 Aug 19,"['Zhao, Rongmao', 'Cui, Shujuan', 'Guo, Li', 'Wu, Chao', 'Gonzalez, Richard', 'Paranhos-Baccalà, Gláucia', 'Vernet, Guy', 'Wang, Jianwei', 'Hung, Tao']",PLoS One,,,True
2fe52e4cee440e3ca69f615221a85064b0641e0c,PMC,Intensive care of the cancer patient: recent achievements and remaining challenges,http://dx.doi.org/10.1186/2110-5820-1-5,PMC3159899,21906331,CC BY,"A few decades have passed since intensive care unit (ICU) beds have been available for critically ill patients with cancer. Although the initial reports showed dismal prognosis, recent data suggest that an increased number of patients with solid and hematological malignancies benefit from intensive care support, with dramatically decreased mortality rates. Advances in the management of the underlying malignancies and support of organ dysfunctions have led to survival gains in patients with life-threatening complications from the malignancy itself, as well as infectious and toxic adverse effects related to the oncological treatments. In this review, we will appraise the prognostic factors and discuss the overall perspective related to the management of critically ill patients with cancer. The prognostic significance of certain factors has changed over time. For example, neutropenia or autologous bone marrow transplantation (BMT) have less adverse prognostic implications than two decades ago. Similarly, because hematologists and oncologists select patients for ICU admission based on the characteristics of the malignancy, the underlying malignancy rarely influences short-term survival after ICU admission. Since the recent data do not clearly support the benefit of ICU support to unselected critically ill allogeneic BMT recipients, more outcome research is needed in this subgroup. Because of the overall increased survival that has been reported in critically ill patients with cancer, we outline an easy-to-use and evidence-based ICU admission triage criteria that may help avoid depriving life support to patients with cancer who can benefit. Lastly, we propose a research agenda to address unanswered questions.",2011 Mar 23,"['Azoulay, Elie', 'Soares, Marcio', 'Darmon, Michael', 'Benoit, Dominique', 'Pastores, Stephen', 'Afessa, Bekele']",Ann Intensive Care,,,True
3775869c0c45f1f0c92eec1d68f9b10827d299f3,PMC,Chinese Herbal Formula Xiao Yao San for Treatment of Depression: A Systematic Review of Randomized Controlled Trials,http://dx.doi.org/10.1155/2012/931636,PMC3159992,21869903,CC BY,"Objectives. To assess the beneficial and adverse effects of Xiaoyaosan for depression. Search Strategy. Electronic databases were searched until December 2009. Inclusion Criteria. We included randomized clinical trials testing Xiaoyaosan against placebo, antidepressants, or combined with antidepressants against antidepressants alone. Data Extraction and Analyses. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards. Results. 26 randomized trials (involving 1837 patients) were included and the methodological quality was evaluated as generally low. The pooled results showed that Xiaoyaosan combined with antidepressants was more effective in comprehensive effect, the score of HAMD and the score of SDS compared with antidepressants alone. Xiaoyaosan was superior to antidepressants for the score of HAMD. However, Xiaoyaosan was not different from placebo for the score of SDS. There was no adverse effects reported in the trials from Xiaoyaosan. Conclusions. Xiaoyaosan appears to be effective on improving symptoms in patients with depression. However, due to poor methodological quality in the majority of included trials, the potential benefit from Xiaoyaosan need to be confirmed in rigorous trials and the design and reporting of trials should follow international standards.",2012 Aug 22,"['Zhang, Yuqing', 'Han, Mei', 'Liu, Zhijun', 'Wang, Jie', 'He, Qingyong', 'Liu, Jianping']",Evid Based Complement Alternat Med,,,True
cc5bd8ae2cac9621202c04c1ec25699f5b7c3a91,PMC,Preventing the next 'SARS' - European healthcare workers' attitudes towards monitoring their health for the surveillance of newly emerging infections: qualitative study,http://dx.doi.org/10.1186/1471-2458-11-541,PMC3160373,21740552,CC BY,"BACKGROUND: Hospitals are often the epicentres of newly circulating infections. Healthcare workers (HCWs) are at high risk of acquiring infectious diseases and may be among the first to contract emerging infections. This study aims to explore European HCWs' perceptions and attitudes towards monitoring their absence and symptom reports for surveillance of newly circulating infections. METHODS: A qualitative study with thematic analysis was conducted using focus group methodology. Forty-nine hospital-based HCWs from 12 hospitals were recruited to six focus groups; two each in England and Hungary and one each in Germany and Greece. RESULTS: HCWs perceived risk factors for occupationally acquired infectious diseases to be 1.) exposure to patients with undiagnosed infections 2.) break-down in infection control procedures 3.) immuno-naïvety and 4.) symptomatic colleagues. They were concerned that a lack of monitoring and guidelines for infectious HCWs posed a risk to staff and patients and felt employers failed to take a positive interest in their health. Staffing demands and loss of income were noted as pressures to attend work when unwell. In the UK, Hungary and Greece participants felt monitoring staff absence and the routine disclosure of symptoms could be appropriate provided the effectiveness and efficiency of such a system were demonstrable. In Germany, legislation, privacy and confidentiality were identified as barriers. All HCWs highlighted the need for knowledge and structural improvements for timelier recognition of emerging infections. These included increased suspicion and awareness among staff and standardised, homogenous absence reporting systems. CONCLUSIONS: Monitoring absence and infectious disease symptom reports among HCWs may be a feasible means of surveillance for emerging infections in some settings. A pre-requisite will be tackling the drivers for symptomatic HCWs to attend work.",2011 Jul 8,"['Aghaizu, Adamma', 'Elam, Gillian', 'Ncube, Fortune', 'Thomson, Gail', 'Szilágyi, Emese', 'Eckmanns, Tim', 'Poulakou, Garyphallia', 'Catchpole, Mike']",BMC Public Health,,,True
66e863b67f8ef14a8a953841b6ddf7a2cefaf696,PMC,Estimating Incidence Curves of Several Infections Using Symptom Surveillance Data,http://dx.doi.org/10.1371/journal.pone.0023380,PMC3160845,21887246,CC BY,"We introduce a method for estimating incidence curves of several co-circulating infectious pathogens, where each infection has its own probabilities of particular symptom profiles. Our deconvolution method utilizes weekly surveillance data on symptoms from a defined population as well as additional data on symptoms from a sample of virologically confirmed infectious episodes. We illustrate this method by numerical simulations and by using data from a survey conducted on the University of Michigan campus. Last, we describe the data needs to make such estimates accurate.",2011 Aug 24,"['Goldstein, Edward', 'Cowling, Benjamin J.', 'Aiello, Allison E.', 'Takahashi, Saki', 'King, Gary', 'Lu, Ying', 'Lipsitch, Marc']",PLoS One,,,True
5a5e5fb3101062ab42831dae0bf504fd3e3a41f1,PMC,Prediction of Peptide Reactivity with Human IVIg through a Knowledge-Based Approach,http://dx.doi.org/10.1371/journal.pone.0023616,PMC3160895,21887285,CC BY,"The prediction of antibody-protein (antigen) interactions is very difficult due to the huge variability that characterizes the structure of the antibodies. The region of the antigen bound to the antibodies is called epitope. Experimental data indicate that many antibodies react with a panel of distinct epitopes (positive reaction). The Challenge 1 of DREAM5 aims at understanding whether there exists rules for predicting the reactivity of a peptide/epitope, i.e., its capability to bind to human antibodies. DREAM 5 provided a training set of peptides with experimentally identified high and low reactivities to human antibodies. On the basis of this training set, the participants to the challenge were asked to develop a predictive model of reactivity. A test set was then provided to evaluate the performance of the model implemented so far. We developed a logistic regression model to predict the peptide reactivity, by facing the challenge as a machine learning problem. The initial features have been generated on the basis of the available knowledge and the information reported in the dataset. Our predictive model had the second best performance of the challenge. We also developed a method, based on a clustering approach, able to “in-silico” generate a list of positive and negative new peptide sequences, as requested by the DREAM5 “bonus round” additional challenge. The paper describes the developed model and its results in terms of reactivity prediction, and highlights some open issues concerning the propensity of a peptide to react with human antibodies.",2011 Aug 24,"['Barbarini, Nicola', 'Tiengo, Alessandra', 'Bellazzi, Riccardo']",PLoS One,,,True
9bbaed357d3aa8c39af2508fb1ca775f8708ec41,PMC,"Molecular Basis of NDM-1, a New Antibiotic Resistance Determinant",http://dx.doi.org/10.1371/journal.pone.0023606,PMC3161043,21887283,CC BY,"The New Delhi Metallo-β-lactamase (NDM-1) was first reported in 2009 in a Swedish patient. A recent study reported that Klebsiella pneumonia NDM-1 positive strain or Escherichia coli NDM-1 positive strain was highly resistant to all antibiotics tested except tigecycline and colistin. These can no longer be relied on to treat infections and therefore, NDM-1 now becomes potentially a major global health threat. In this study, we performed modeling studies to obtain its 3D structure and NDM-1/antibiotics complex. It revealed that the hydrolytic mechanisms are highly conserved. In addition, the detailed analysis indicates that the more flexible and hydrophobic loop1, together with the evolution of more positive-charged loop2 leads to NDM-1 positive strain more potent and extensive in antibiotics resistance compared with other MBLs. Furthermore, through biological experiments, we revealed the molecular basis for antibiotics catalysis of NDM-1 on the enzymatic level. We found that NDM-1 enzyme was highly potent to degrade carbapenem antibiotics, while mostly susceptible to tigecycline, which had the ability to slow down the hydrolysis velocity of meropenem by NDM-1. Meanwhile, the mutagenesis experiments, including D124A, C208A, K211A and K211E, which displayed down-regulation on meropenem catalysis, proved the accuracy of our model. At present, there are no effective antibiotics against NDM-1 positive pathogen. Our study will provide clues to investigate the molecular basis of extended antibiotics resistance of NDM-1 and then accelerate the search for new antibiotics against NDM-1 positive strain in clinical studies.",2011 Aug 24,"['Liang, Zhongjie', 'Li, Lianchun', 'Wang, Yuanyuan', 'Chen, Limin', 'Kong, Xiangqian', 'Hong, Yao', 'Lan, Lefu', 'Zheng, Mingyue', 'Guang-Yang, Cai', 'Liu, Hong', 'Shen, Xu', 'Luo, Cheng', 'Li, Keqin Kathy', 'Chen, Kaixian', 'Jiang, Hualiang']",PLoS One,,,True
c92d4b764634f984f72efccaa63b365bebc10616,PMC,Phage Displayed Peptides to Avian H5N1 Virus Distinguished the Virus from Other Viruses,http://dx.doi.org/10.1371/journal.pone.0023058,PMC3161733,21887228,CC BY,"The purpose of the current study was to identify potential ligands and develop a novel diagnostic test to highly pathogenic avian influenza A virus (HPAI), subtype H5N1 viruses using phage display technology. The H5N1 viruses were used as an immobilized target in a biopanning process using a 12-mer phage display random peptide library. After five rounds of panning, three phages expressing peptides HAWDPIPARDPF, AAWHLIVALAPN or ATSHLHVRLPSK had a specific binding activity to H5N1 viruses were isolated. Putative binding motifs to H5N1 viruses were identified by DNA sequencing. In terms of the minimum quantity of viruses, the phage-based ELISA was better than antiserum-based ELISA and a manual, semi-quantitative endpoint RT-PCR for detecting H5N1 viruses. More importantly, the selected phages bearing the specific peptides to H5N1 viruses were capable of differentiating this virus from other avian viruses in enzyme-linked immunosorbent assays.",2011 Aug 22,"['Wu, Dan', 'Li, Guangxing', 'Qin, Chengfeng', 'Ren, Xiaofeng']",PLoS One,,,True
d1f35ee252fdb019a824ad4778e8e220c27fc608,PMC,Inhibition of SARS Pseudovirus Cell Entry by Lactoferrin Binding to Heparan Sulfate Proteoglycans,http://dx.doi.org/10.1371/journal.pone.0023710,PMC3161750,21887302,CC BY,"It has been reported that lactoferrin (LF) participates in the host immune response against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) invasion by enhancing NK cell activity and stimulating neutrophil aggregation and adhesion. We further investigated the role of LF in the entry of SARS pseudovirus into HEK293E/ACE2-Myc cells. Our results reveal that LF inhibits SARS pseudovirus infection in a dose-dependent manner. Further analysis suggested that LF was able to block the binding of spike protein to host cells at 4°C, indicating that LF exerted its inhibitory function at the viral attachment stage. However, LF did not disrupt the interaction of spike protein with angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV. Previous studies have shown that LF colocalizes with the widely distributed cell-surface heparan sulfate proteoglycans (HSPGs). Our experiments have also confirmed this conclusion. Treatment of the cells with heparinase or exogenous heparin prevented binding of spike protein to host cells and inhibited SARS pseudovirus infection, demonstrating that HSPGs provide the binding sites for SARS-CoV invasion at the early attachment phase. Taken together, our results suggest that, in addition to ACE2, HSPGs are essential cell-surface molecules involved in SARS-CoV cell entry. LF may play a protective role in host defense against SARS-CoV infection through binding to HSPGs and blocking the preliminary interaction between SARS-CoV and host cells. Our findings may provide further understanding of SARS-CoV pathogenesis and aid in treatment of this deadly disease.",2011 Aug 22,"['Lang, Jianshe', 'Yang, Ning', 'Deng, Jiejie', 'Liu, Kangtai', 'Yang, Peng', 'Zhang, Guigen', 'Jiang, Chengyu']",PLoS One,,,True
8f26b1ab1d54522ce151927a8cb48cf52058961a,PMC,Identification of M.tuberculosis-Specific Th1 Cells Expressing CD69 Generated in vivo in Pleural Fluid Cells from Patients with Tuberculous Pleurisy,http://dx.doi.org/10.1371/journal.pone.0023700,PMC3161751,21887301,CC BY,"Th1 cell-mediated immune responses at the site of active infection are important to restrict the growth of M.tuberculosis (MTB) and for the spontaneous resolution of patients with tuberculous pleurisy (TBP). In the present study, we found that without any stimulation, CD4(+) T cells in pleural fluid cells (PFCs) from patients with TBP expressed significantly higher levels of CD69 than PBMCs from patients with tuberculosis (TB) or healthy donors. CD4(+)CD69(+) T cells expressed T-bet and IL-12Rβ2. After stimulation with MTB-specific antigens, CD4(+)CD69(+) T cells expressed significantly higher levels of IFN-γ, IL-2 and TNF-α than CD4(+)CD69(−) T cells, demonstrating that CD4(+)CD69(+) T cells were MTB-specific Th1 cells. In addition, CD4(+)CD69(+) T cells were mostly polyfunctional Th1 cells that simultaneously produced IFN-γ, IL-2, TNF-α and displayed an effector or effector memory phenotype (CD45RA(−)CCR7(−)CD62L(−)CD27(−)). Moreover, the percentages of CD4(+)CD69(+) T cells were significantly and positively correlated with polyfunctional T cells. Interestingly, sorted CD4(+)CD69(+) but not CD4(+)CD69(−) fractions by flow cytometry produced IFN-γ, IL-2 and TNF-α that were significantly regulated by CD4(+)CD25(+) Treg cells. Taken together, based on the expression of CD69, we found a direct quantitative and qualitative method to detect and evaluate the in vivo generated MTB-specific polyfunctional CD4(+) T cells in PFCs from patients with TBP. This method can be used for the potential diagnosis and enrichment or isolation of MTB-specific Th1 cells in the investigations.",2011 Aug 22,"['Li, Li', 'Qiao, Dan', 'Fu, Xiaoying', 'Lao, Suihua', 'Zhang, Xianlan', 'Wu, Changyou']",PLoS One,,,True
a03298211c385b7bd1d1ebdc98b1cc69efe7f54d,PMC,"Systematic Identification of Novel, Essential Host Genes Affecting Bromovirus RNA Replication",http://dx.doi.org/10.1371/journal.pone.0023988,PMC3161824,21915247,CC BY,"Positive-strand RNA virus replication involves viral proteins and cellular proteins at nearly every replication step. Brome mosaic virus (BMV) is a well-established model for dissecting virus-host interactions and is one of very few viruses whose RNA replication, gene expression and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae. Previously, our laboratory identified ∼100 non-essential host genes whose loss inhibited or enhanced BMV replication at least 3-fold. However, our isolation of additional BMV-modulating host genes by classical genetics and other results underscore that genes essential for cell growth also contribute to BMV RNA replication at a frequency that may be greater than that of non-essential genes. To systematically identify novel, essential host genes affecting BMV RNA replication, we tested a collection of ∼900 yeast strains, each with a single essential gene promoter replaced by a doxycycline-repressible promoter, allowing repression of gene expression by adding doxycycline to the growth medium. Using this strain array of ∼81% of essential yeast genes, we identified 24 essential host genes whose depleted expression reproducibly inhibited or enhanced BMV RNA replication. Relevant host genes are involved in ribosome biosynthesis, cell cycle regulation and protein homeostasis, among other cellular processes. BMV 2a(Pol) levels were significantly increased in strains depleted for a heat shock protein (HSF1) or proteasome components (PRE1 and RPT6), suggesting these genes may affect BMV RNA replication by directly or indirectly modulating 2a(Pol) localization, post-translational modification or interacting partners. Investigating the diverse functions of these newly identified essential host genes should advance our understanding of BMV-host interactions and normal cellular pathways, and suggest new modes of virus control.",2011 Aug 22,"['Gancarz, Brandi L.', 'Hao, Linhui', 'He, Qiuling', 'Newton, Michael A.', 'Ahlquist, Paul']",PLoS One,,,True
d0acac75cb3d2c19abfe061a5b1530b1dbbc6922,PMC,Dominating Biological Networks,http://dx.doi.org/10.1371/journal.pone.0023016,PMC3162560,21887225,CC BY,"Proteins are essential macromolecules of life that carry out most cellular processes. Since proteins aggregate to perform function, and since protein-protein interaction (PPI) networks model these aggregations, one would expect to uncover new biology from PPI network topology. Hence, using PPI networks to predict protein function and role of protein pathways in disease has received attention. A debate remains open about whether network properties of “biologically central (BC)” genes (i.e., their protein products), such as those involved in aging, cancer, infectious diseases, or signaling and drug-targeted pathways, exhibit some topological centrality compared to the rest of the proteins in the human PPI network. To help resolve this debate, we design new network-based approaches and apply them to get new insight into biological function and disease. We hypothesize that BC genes have a topologically central (TC) role in the human PPI network. We propose two different concepts of topological centrality. We design a new centrality measure to capture complex wirings of proteins in the network that identifies as TC those proteins that reside in dense extended network neighborhoods. Also, we use the notion of domination and find dominating sets (DSs) in the PPI network, i.e., sets of proteins such that every protein is either in the DS or is a neighbor of the DS. Clearly, a DS has a TC role, as it enables efficient communication between different network parts. We find statistically significant enrichment in BC genes of TC nodes and outperform the existing methods indicating that genes involved in key biological processes occupy topologically complex and dense regions of the network and correspond to its “spine” that connects all other network parts and can thus pass cellular signals efficiently throughout the network. To our knowledge, this is the first study that explores domination in the context of PPI networks.",2011 Aug 26,"['Milenković, Tijana', 'Memišević, Vesna', 'Bonato, Anthony', 'Pržulj, Nataša']",PLoS One,,,True
804df67d9b05a58b34332c92efec930254f5ebe3,PMC,A review of bronchiolitis obliterans syndrome and therapeutic strategies,http://dx.doi.org/10.1186/1749-8090-6-92,PMC3162889,21767391,CC BY,"Lung transplantation is an important treatment option for patients with advanced lung disease. Survival rates for lung transplant recipients have improved; however, the major obstacle limiting better survival is bronchiolitis obliterans syndrome (BOS). In the last decade, survival after lung retransplantation has improved for transplant recipients with BOS. This manuscript reviews BOS along with the current therapeutic strategies, including recent outcomes for lung retransplantation.",2011 Jul 18,"Hayes, Don",J Cardiothorac Surg,,,True
f7417991beaa7bd0483f9dbdd549c12eeee26508,PMC,Poly(I:C) promotes TNFα/TNFR1-dependent oligodendrocyte death in mixed glial cultures,http://dx.doi.org/10.1186/1742-2094-8-89,PMC3162898,21812954,CC BY,"BACKGROUND: Activation of glial cells via toll-like receptors (TLRs) and other intracellular pathogen recognition receptors promotes the release of potentially toxic acute phase reactants such as TNFα and nitric oxide into the extracellular space. As such, prolonged glial activation, as is thought to occur during a persistent viral infection of the CNS, may contribute to both neurodegeneration and demyelination. However, the effects of virus-induced glial activation on oligodendrocytes are not fully understood. METHOD: To determine the effects of glial activation on oligodendrocyte viability we treated primary glial cultures isolated from neonatal rats or mice with the RNA viral mimic poly(I:C) and in some cases other TLR ligands. TLR3 expression was determined by western blot. Cytokine levels were measured by RT-PCR, ELISA, and intracellular cytokine staining. Oligodendrocyte precursor (preOL) viability was determined by Alamar blue assays and immunocytochemistry. RESULT: Stimulation of mixed glial cultures with poly(I:C) resulted in microglia activation, TNFα production and preOL toxicity. This toxic effect of poly(I:C) was indirect as it failed to affect preOL viability in pure cultures despite the fact that preOLs express TLR3. Poly(I:C)-induced loss of preOLs was abolished in TNFα or TNFR1 deficient mixed glial cultures, suggesting that TNFα/TNFR1 signaling is required for poly(I:C) toxicity. Furthermore, although both microglia and astrocytes express functional TLR3, only microglia produced TNFα in culture. Consistent with these findings, other TLR agonists similarly triggered TNFα production and preOL toxicity in mixed glial cultures. CONCLUSION: Activation of microglia by poly(I:C) promotes TNFα/TNFR1-dependent oligodendroglial cell death. These data indicate that during an ongoing viral infection of the CNS, microglial TNFα may be detrimental to oligodendrocytes.",2011 Aug 3,"['Steelman, Andrew J', 'Li, Jianrong']",J Neuroinflammation,,,True
f1301ca67dfb936ebc49c73777088997c3fc23a6,PMC,Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances,http://dx.doi.org/10.3797/scipharm.1012-08,PMC3163371,21886894,CC BY,"Human African Trypanosomiasis (HAT) also called sleeping sickness is caused by subspecies of the parasitic hemoflagellate Trypanosoma brucei that mostly occurs in sub-Saharan Africa. The current chemotherapy of the human trypanosomiases relies on only six drugs, five of which have been developed more than 30 years ago, have undesirable toxic side effects and most of them show drug-resistance. Though development of new anti-trypanosomal drugs seems to be a priority area research in this area has lagged far behind. The given review mainly focus upon the recent synthetic and computer based approaches made by various research groups for the development of newer anti-trypanosomal analogues which may have improved efficacy and oral bioavailability than the present ones. The given paper also attempts to investigate the relationship between the various physiochemical parameters and anti-trypanosomal activity that may be helpful in development of potent anti-trypanosomal agents against sleeping sickness.",2011 May 10 Jul-Sep,"['Paliwal, Sarvesh K.', 'Verma, Ankita Narayan', 'Paliwal, Shailendra']",Sci Pharm,,,True
12af3b3c07569926eb1ce96ebd4d5bffd05ce54a,PMC,Genetic Variation of the Human α-2-Heremans-Schmid Glycoprotein (AHSG) Gene Associated with the Risk of SARS-CoV Infection,http://dx.doi.org/10.1371/journal.pone.0023730,PMC3163911,21904596,CC BY,"Genetic background may play an important role in the process of SARS-CoV infection and SARS development. We found several proteins that could interact with the nucleocapsid protein of the SARS coronavirus (SARS-CoV). α-2-Heremans-Schmid Glycoprotein (AHSG), which is required for macrophage deactivation by endogenous cations, is associated with inflammatory regulation. Cytochrome P450 Family 3A (CYP4F3A) is an ω-oxidase that inactivates Leukotriene B4 (LTB4) in human neutrophils and the liver. We investigated the association between the polymorphisms of these two inflammation-associated genes and SARS development. The linkage disequilibrium (LD) maps of these two genes were built with Haploview using data on CHB+JPT (version 2) from the HapMap. A total of ten tag SNPs were selected and genotyped. In the Guangzhou cohort study, after adjusting for age and sex, two AHSG SNPs and one CYP4F3 SNP were found to be associated with SARS susceptibility: rs2248690 (adjusted odds ratio [AOR] 2.42; 95% confidence interval [CI] 1.30-4.51); rs4917 (AOR 1.84; 95% CI 1.02-3.34); and rs3794987 (AOR 2.01; 95% CI 1.10–3.68). To further validate the association, the ten tag SNPs were genotyped in the Beijing cohort. After adjusting for age and sex, only rs2248690 (AOR, 1.63; 95% CI, 1.30–2.04) was found to be associated with SARS susceptibility. The combined analysis of the two studies confirmed tag SNP rs2248690 in AHSG as a susceptibility variant (AOR 1.70; 95% CI 1.37–2.09). The statistical analysis of the rs2248690 genotype data among the patients and healthy controls in the HCW cohort, who were all similarly exposed to the SARS virus, also supported the findings. Further, the SNP rs2248690 affected the transcriptional activity of the AHSG promoter and thus regulated the AHSG serum level. Therefore, our study has demonstrated that the AA genotype of rs2268690, which leads to a higher AHSG serum concentration, was significantly associated with protection against SARS development.",2011 Aug 17,"['Zhu, Xiaohui', 'Wang, Yan', 'Zhang, Hongxing', 'Liu, Xuan', 'Chen, Ting', 'Yang, Ruifu', 'Shi, Yuling', 'Cao, Wuchun', 'Li, Ping', 'Ma, Qingjun', 'Zhai, Yun', 'He, Fuchu', 'Zhou, Gangqiao', 'Cao, Cheng']",PLoS One,,,True
a73d97226cb958a94cd359666b35e092452818b7,PMC,Chlamydia trachomatis Co-opts GBF1 and CERT to Acquire Host Sphingomyelin for Distinct Roles during Intracellular Development,http://dx.doi.org/10.1371/journal.ppat.1002198,PMC3164637,21909260,CC BY,"The obligate intracellular pathogen Chlamydia trachomatis replicates within a membrane-bound inclusion that acquires host sphingomyelin (SM), a process that is essential for replication as well as inclusion biogenesis. Previous studies demonstrate that SM is acquired by a Brefeldin A (BFA)-sensitive vesicular trafficking pathway, although paradoxically, this pathway is dispensable for bacterial replication. This finding suggests that other lipid transport mechanisms are involved in the acquisition of host SM. In this work, we interrogated the role of specific components of BFA-sensitive and BFA-insensitive lipid trafficking pathways to define their contribution in SM acquisition during infection. We found that C. trachomatis hijacks components of both vesicular and non-vesicular lipid trafficking pathways for SM acquisition but that the SM obtained from these separate pathways is being utilized by the pathogen in different ways. We show that C. trachomatis selectively co-opts only one of the three known BFA targets, GBF1, a regulator of Arf1-dependent vesicular trafficking within the early secretory pathway for vesicle-mediated SM acquisition. The Arf1/GBF1-dependent pathway of SM acquisition is essential for inclusion membrane growth and stability but is not required for bacterial replication. In contrast, we show that C. trachomatis co-opts CERT, a lipid transfer protein that is a key component in non-vesicular ER to trans-Golgi trafficking of ceramide (the precursor for SM), for C. trachomatis replication. We demonstrate that C. trachomatis recruits CERT, its ER binding partner, VAP-A, and SM synthases, SMS1 and SMS2, to the inclusion and propose that these proteins establish an on-site SM biosynthetic factory at or near the inclusion. We hypothesize that SM acquired by CERT-dependent transport of ceramide and subsequent conversion to SM is necessary for C. trachomatis replication whereas SM acquired by the GBF1-dependent pathway is essential for inclusion growth and stability. Our results reveal a novel mechanism by which an intracellular pathogen redirects SM biosynthesis to its replicative niche.",2011 Sep 1,"['Elwell, Cherilyn A.', 'Jiang, Shaobo', 'Kim, Jung Hwa', 'Lee, Albert', 'Wittmann, Torsten', 'Hanada, Kentaro', 'Melancon, Paul', 'Engel, Joanne N.']",PLoS Pathog,,,True
fbb13d5bcfe0597fc854533fa1637fd4c415bb5a,PMC,A Recombinant Avian Infectious Bronchitis Virus Expressing a Heterologous Spike Gene Belonging to the 4/91 Serotype,http://dx.doi.org/10.1371/journal.pone.0024352,PMC3166170,21912629,CC BY,"We have shown previously that replacement of the spike (S) gene of the apathogenic IBV strain Beau-R with that from the pathogenic strain of the same serotype, M41, resulted in an apathogenic virus, BeauR-M41(S), that conferred protection against challenge with M41 [1]. We have constructed a recombinant IBV, BeauR-4/91(S), with the genetic backbone of Beau-R but expressing the spike protein of the pathogenic IBV strain 4/91(UK), which belongs to a different serogroup as Beaudette or M41. Similar to our previous findings with BeauR-M41(S), clinical signs observations showed that the S gene of the pathogenic 4/91 virus did not confer pathogenicity to the rIBV BeauR-4/91(S). Furthermore, protection studies showed there was homologous protection; BeauR-4/91(S) conferred protection against challenge with wild type 4/91 virus as shown by the absence of clinical signs, IBV RNA assessed by qRT-PCR and the fact that no virus was isolated from tracheas removed from birds primarily infected with BeauR-4/91(S) and challenged with IBV 4/91(UK). A degree of heterologous protection against M41 challenge was observed, albeit at a lower level. Our results confirm and extend our previous findings and conclusions that swapping of the ectodomain of the S protein is a precise and effective way of generating genetically defined candidate IBV vaccines.",2011 Aug 30,"['Armesto, Maria', 'Evans, Sharon', 'Cavanagh, David', 'Abu-Median, Abu-Bakr', 'Keep, Sarah', 'Britton, Paul']",PLoS One,,,True
4409a3d523a0e35a95671bb6d947c39763bd0bb0,PMC,NoD: a Nucleolar localization sequence detector for eukaryotic and viral proteins,http://dx.doi.org/10.1186/1471-2105-12-317,PMC3166288,21812952,CC BY,"BACKGROUND: Nucleolar localization sequences (NoLSs) are short targeting sequences responsible for the localization of proteins to the nucleolus. Given the large number of proteins experimentally detected in the nucleolus and the central role of this subnuclear compartment in the cell, NoLSs are likely to be important regulatory elements controlling cellular traffic. Although many proteins have been reported to contain NoLSs, the systematic characterization of this group of targeting motifs has only recently been carried out. RESULTS: Here, we describe NoD, a web server and a command line program that predicts the presence of NoLSs in proteins. Using the web server, users can submit protein sequences through the NoD input form and are provided with a graphical output of the NoLS score as a function of protein position. While the web server is most convenient for making prediction for just a few proteins, the command line version of NoD can return predictions for complete proteomes. NoD is based on our recently described human-trained artificial neural network predictor. Through stringent independent testing of the predictor using available experimentally validated NoLS-containing eukaryotic and viral proteins, the NoD sensitivity and positive predictive value were estimated to be 71% and 79% respectively. CONCLUSIONS: NoD is the first tool to provide predictions of nucleolar localization sequences in diverse eukaryotes and viruses. NoD can be run interactively online at http://www.compbio.dundee.ac.uk/nod or downloaded to use locally.",2011 Aug 3,"['Scott, Michelle S', 'Troshin, Peter V', 'Barton, Geoffrey J']",BMC Bioinformatics,,,True
24d7fe6bbb9945f1536fef5b281d074fe69cfc6a,PMC,Avian Influenza Risk Perception and Preventive Behavior among Traditional Market Workers and Shoppers in Taiwan: Practical Implications for Prevention,http://dx.doi.org/10.1371/journal.pone.0024157,PMC3166308,21912667,CC BY,"BACKGROUND: Avian influenza (AI) can be highly pathogenic and fatal. Preventive behavior such as handwashing and wearing face masks has been recommended. However, little is known about what psychosocial factors might influence people's decision to adopt such preventive behavior. This study aims to explore risk perception and other factors associated with handwashing and wearing face masks to prevent AI. METHODOLOGY/PRINCIPAL FINDINGS: An interviewer-administered survey was conducted among 352 traditional market workers and shoppers in Taiwan between December 2009 and January 2010. Factors associated with the recommended AI preventive behavior (i.e., when in a traditional market, wearing a face mask and also washing hands after any contact with poultry) included: having correct knowledge about the fatality rate of AI (adjusted odds ratio [AOR] = 4.18), knowing of severe cases of AI (AOR = 2.13), being informed of local AI outbreaks (AOR = 2.24), living in northeastern Taiwan (AOR = 6.01), having a senior high-school education (AOR = 3.33), and having a university or higher education (AOR = 6.86). Gender interactive effect was also found among participants with a senior high-school education, with males being less likely to engage in the recommended AI preventive behavior than their female counterparts (AOR = 0.34). CONCLUSIONS/SIGNIFICANCE: Specific information concerning AI risk perception was associated with the recommended AI preventive behavior. In particular, having correct knowledge about the fatality rate of AI and being informed of severe cases and local outbreaks of AI were linked to increased AI preventive behavior. These findings underscore the importance of transparency in dealing with epidemic information. These results also have practical implications for prevention and policy-making to more effectively promote the recommended AI preventive behavior in the public.",2011 Sep 2,"['Kuo, Pei-Chun', 'Huang, Jiun-Hau', 'Liu, Ming-Der']",PLoS One,,,True
259ac67e44e833ea06564160ee399b76985f1145,PMC,Plasma proteomic profile of sulfur mustard exposed lung diseases patients using 2-dimensional gel electrophoresis,http://dx.doi.org/10.1186/1559-0275-8-2,PMC3167199,21906349,CC BY,"INTRODUCTION: Sulfur mustard ""bis (2-chlroethyl) sulphide"" (SM) is a chemical warfare agent that remains a threat to human health. The aim of this study was to identify protein expression signature or biomarkers that reflect chronic lung damages induced by SM exposure. METHODS: Prior to analysis, plasma was fractionated using ethanol precipitation. Using two dimensional SDS-PAGE; fractionated protein profiles of 20 healthy and 20 exposed patients with lung diseases were established. Selected protein spots were successfully identified with MALDI TOF MS/MS. RESULTS: The results show that α1 haptoglobin isoforms were detected in plasma of the all lung disease patients but none of the healthy controls. Amyloid A1 isoforms was also detected in plasma of the lung disease patients but none of the healthy controls. Moreover, low molecular weight proteins were enriched in ethanol supernatant compared to ethanol precipitate. CONCLUSION: Our present results and previous studies suggest that ongoing tissue remodeling is involved in SM exposed lung damage patients. These finding might improve patient care and suitable therapies.",2011 Jan 7,"['Mehrani, Hossein', 'Ghanei, Mostafa', 'Aslani, Jafar', 'Tabatabaei, Zahra']",Clin Proteomics,,,True
b5c6a1c48730f12db7c74e51ca05a54fb4a9d202,PMC,Population response to the risk of vector-borne diseases: lessons learned from socio-behavioural research during large-scale outbreaks,http://dx.doi.org/10.3134/ehtj.09.006,PMC3167643,22460287,CC BY,"Vector-borne infectious diseases, such as malaria, dengue, chikungunya, and West Nile fevers are increasingly identified as major global human health threats in developing and developed countries. The success or failure of vector control rests mainly on the nature and scale of the behavioural response of exposed populations. Large-scale adoption of recommended protective behaviour represents a critical challenge that cannot be addressed without a better understanding of how individuals perceive and react to the risk of infection. Recently, French overseas territories faced large-scale outbreaks: an epidemic of chikungunya fever in La Re′ union and Mayotte (2005–2006) and four successive outbreaks of dengue fever in one Caribbean island, Martinique (1995–2007). To assess how these populations perceived and responded to the risk, and how the nature and scale of protection affected their clinical status, socio-epidemiological surveys were conducted on each island during the outbreaks. These surveys address three crucial and interconnected questions relevant to the period after persons infected by the virus were identified: which factors shape the risk of acquiring disease? Which socio- demographic characteristics and living conditions induce a higher likelihood of infection? What is the impact of risk perception on protective behaviours adopted against mosquito bites? Grounded on the results of these surveys, a general framework is proposed to help draw out the knowledge needed to reveal the factors associated with higher probability of infection as an outbreak emerges. The lessons learnt can inform health authorities’ efforts to improve risk communication programmes, both in terms of the target and content of messages, so as to explore new strategies for ensuring sustainable protective behaviour. The authors compare three epidemics of vector-borne diseases to elucidate psychosocial factors that determine how populations perceive and respond to the risk of infectious disease.",2009 Jul 31,"['Setbon, M', 'Raude, J']",Emerg Health Threats J,,,True
b817c40ff2740be4fb203fbef15d27aa6e25c299,PMC,"Migrants and emerging public health issues in a globalized world: threats, risks and challenges, an evidence-based framework",http://dx.doi.org/10.3134/ehtj.09.010,PMC3167650,22460280,CC BY,"International population mobility is an underlying factor in the emergence of public health threats and risks that must be managed globally. These risks are often related, but not limited, to transmissible pathogens. Mobile populations can link zones of disease emergence to lowprevalence or nonendemic areas through rapid or high-volume international movements, or both. Against this background of human movement, other global processes such as economics, trade, transportation, environment and climate change, as well as civil security influence the health impacts of disease emergence. Concurrently, global information systems, together with regulatory frameworks for disease surveillance and reporting, affect organizational and public awareness of events of potential public health significance. International regulations directed at disease mitigation and control have not kept pace with the growing challenges associated with the volume, speed, diversity, and disparity of modern patterns of human movement. The thesis that human population mobility is itself a major determinant of global public health is supported in this article by review of the published literature from the perspective of determinants of health (such as genetics/biology, behavior, environment, and socioeconomics), population-based disease prevalence differences, existing national and international health policies and regulations, as well as inter-regional shifts in population demographics and health outcomes. This paper highlights some of the emerging threats and risks to public health, identifies gaps in existing frameworks to manage health issues associated with migration, and suggests changes in approach to population mobility, globalization, and public health. The proposed integrated approach includes a broad spectrum of stakeholders ranging from individual health-care providers to policy makers and international organizations that are primarily involved in global health management, or are influenced by global health events.",2010 Mar 31,"['Gushulak, BD', 'Weekers, J', 'MacPherson, DW']",Emerg Health Threats J,,,True
813d4108f75af14e71c3b9fdc9281c30ba90b39e,PMC,In the name of the greater good?,http://dx.doi.org/10.3134/ehtj.09.012,PMC3167651,22460282,CC BY,"In the event of a pandemic that poses widespread infection and high death rates, the utilitarian mandate to ‘reduce harm’ is the relevant moral value that trumps other ethical considerations. The primacy of a utilitarian approach dictates that those who are in a position to assist the cessation of the most serious outbreaks in whatever role they may have, must be present to provide their services, and those who administer health care must also be present to ensure that all responders are supported and protected to the highest degree.",2010 Mar 31,"Kirkwood, K",Emerg Health Threats J,,,True
d4d15fb77f993153439d9ebd90c649962ee398e9,PMC,Emerging viral threats in Gabon: health capacities and response to the risk of emerging zoonotic diseases in Central Africa,http://dx.doi.org/10.3134/ehtj.10.163,PMC3167654,22460397,CC BY,"Emerging infectious diseases (EID) are currently the major threat to public health worldwide and most EID events have involved zoonotic infectious agents. Central Africa in general and Gabon in particular are privileged areas for the emergence of zoonotic EIDs. Indeed, human incursions in Gabonese forests for exploitation purposes lead to intensified contacts between humans and wildlife thus generating an increased risk of emergence of zoonotic diseases. In Gabon, 51 endemic or potential endemic viral infectious diseases have been reported. Among them, 22 are of zoonotic origin and involve 12 families of viruses. The most notorious are dengue, yellow fever, ebola, marburg, Rift Valley fever and chikungunya viruses. Potential EID due to wildlife in Gabon are thereby plentiful and need to be inventoried. The Gabonese Public Health system covers geographically most of the country allowing a good access to sanitary information and efficient monitoring of emerging diseases. However, access to treatment and prevention is better in urban areas where medical structures are more developed and financial means are concentrated even though the population is equally distributed between urban and rural areas. In spite of this, Gabon could be a good field for investigating the emergence or re-emergence of zoonotic EID. Indeed Gabonese health research structures such as CIRMF, advantageously located, offer high quality researchers and facilities that study pathogens and wildlife ecology, aiming toward a better understanding of the contact and transmission mechanisms of new pathogens from wildlife to human, the emergence of zoonotic EID and the breaking of species barriers by pathogens.",2010 Jun 3,"['Bourgarel, M', 'Wauquier, N', 'Gonzalez, J-P']",Emerg Health Threats J,,,True
5d9de14dd116027eb2325fc91534d038f8eac88b,PMC,Innovation in observation: a vision for early outbreak detection,http://dx.doi.org/10.3134/ehtj.10.006,PMC3167656,22460396,CC BY,"The emergence of new infections and resurgence of old ones—health threats stemming from environmental contamination or purposeful acts of bioterrorism—call for a worldwide effort in improving early outbreak detection, with the goal of ameliorating current and future risks. In some cases, the problem of outbreak detection is logistically straightforward and mathematically easy: a single case of a disease of great concern can constitute an outbreak. However, for the vast majority of maladies, a simple analytical solution does not exist. Furthermore, each step in developing reliable, sensitive, effective surveillance systems demonstrates enormous complexities in the transmission, manifestation, detection, and control of emerging health threats. In this communication, we explore potential future innovations in early outbreak detection systems that can overcome the pitfalls of current surveillance. We believe that modern advances in assembling data, techniques for collating and processing information, and technology that enables integrated analysis will facilitate a new paradigm in outbreak definition and detection. We anticipate that moving forward in this direction will provide the highly desired sensitivity and specificity in early detection required to meet the emerging challenges of global disease surveillance.",2010 May 20,"['Fefferman, NH', 'Naumova, EN']",Emerg Health Threats J,,,True
c0789cc30e0766ccdea9e216da799f9cb41f853d,PMC,Human rhinovirus C: a newly discovered human rhinovirus species,http://dx.doi.org/10.3134/ehtj.10.002,PMC3167658,22460392,CC BY,"Although often ignored, human rhinoviruses (HRVs) are the most frequent causes of respiratory tract infections (RTIs). A group of closely related novel rhinoviruses have recently been discovered. Based on their unique phylogenetic position and distinct genomic features, they are classified as a separate species, HRV-C. After their discovery, HRV-C viruses have been detected in patients worldwide, with a reported prevalence of 1.4–30.9% among tested specimens. This suggests that the species contribute to a significant proportion of RTIs that were unrecognized in the past. HRV-C is also the predominant HRV species, often with a higher detection rate than that of the two previously known species, HRV-A and HRV-B. HRV-C infections appear to peak in fall or winter in most temperate or subtropical countries, but may predominate in the rainy season in the tropics. In children, HRV-C is often associated with upper RTIs, with asthma exacerbation and wheezing episodes being common complications. The virus has also been detected in children with bronchitis, bronchiolitis, pneumonia, otitis media, sinusitis and systemic infections complicated by pericarditis. As for adults, HRV-C has been associated with more severe disease such as pneumonia and exacerbation of chronic obstructive pulmonary disease. However, larger clinical studies with asymptomatic controls are required to better define the significance of HRV-C infection in the adult population. On the basis of VP4 sequence analysis, a potential distinct subgroup within HRV-C has also been identified, although more complete genome sequences are needed to better define the genetic diversity of HRV-C.",2010 Oct 4,"['LauLau, S K P, SK', 'YipYip, C C Y, CC', 'WooWoo, P C Y, PC', 'Yuen, K-Y']",Emerg Health Threats J,,,True
a6c379baf7fcba6a32b8fdadbcd9a85032dd4729,PMC,Synthetic long oligonucleotides to generate artificial templates for use as positive controls in molecular assays: drug resistance mutations in influenza virus as an example,http://dx.doi.org/10.1186/1743-422X-8-405,PMC3168426,21843374,CC BY,"BACKGROUND: Positive controls are an integral component of any sensitive molecular diagnostic tool, but this can be affected, if several mutations are being screened in a scenario of a pandemic or newly emerging disease where it can be difficult to acquire all the necessary positive controls from the host. This work describes the development of a synthetic oligo-cassette for positive controls for accurate and highly sensitive diagnosis of several mutations relevant to influenza virus drug resistance. RESULTS: Using influenza antiviral drug resistance mutations as an example by employing the utility of synthetic paired long oligonucleotides containing complementary sequences at their 3' ends and utilizing the formation of oligonucleotide dimers and DNA polymerization, we generated ~170bp dsDNA containing several known specific neuraminidase inhibitor (NAI) resistance mutations. These templates were further cloned and successfully applied as positive controls in downstream assays. CONCLUSION: This approach significantly improved the development of diagnosis of resistance mutations in terms of time, accuracy, efficiency and sensitivity, which are paramount to monitoring the emergence and spread of antiviral drug resistant influenza strains. Thus, this may have a significantly broader application in molecular diagnostics along with its application in rapid molecular testing of all relevant mutations in an event of pandemic.",2011 Aug 16,"['Wang, Bin', 'Steain, Megan C', 'Dwyer, Dominic E', 'Cunningham, Anthony L', 'Saksena, Nitin K']",Virol J,,,True
8bb9d8f7eeb8272924275f349e5c63a5bb006445,PMC,Annexin A2 Binds RNA and Reduces the Frameshifting Efficiency of Infectious Bronchitis Virus,http://dx.doi.org/10.1371/journal.pone.0024067,PMC3168876,21918681,CC BY,"Annexin A2 (ANXA2) is a protein implicated in diverse cellular functions, including exocytosis, DNA synthesis and cell proliferation. It was recently proposed to be involved in RNA metabolism because it was shown to associate with some cellular mRNA. Here, we identified ANXA2 as a RNA binding protein (RBP) that binds IBV (Infectious Bronchitis Virus) pseudoknot RNA. We first confirmed the binding of ANXA2 to IBV pseudoknot RNA by ultraviolet crosslinking and showed its binding to RNA pseudoknot with ANXA2 protein in vitro and in the cells. Since the RNA pseudoknot located in the frameshifting region of IBV was used as bait for cellular RBPs, we tested whether ANXA2 could regulate the frameshfting of IBV pseudoknot RNA by dual luciferase assay. Overexpression of ANXA2 significantly reduced the frameshifting efficiency from IBV pseudoknot RNA and knockdown of the protein strikingly increased the frameshifting efficiency. The results suggest that ANXA2 is a cellular RBP that can modulate the frameshifting efficiency of viral RNA, enabling it to act as an anti-viral cellular protein, and hinting at roles in RNA metabolism for other cellular mRNAs.",2011 Aug 30,"['Kwak, Hoyun', 'Park, Min Woo', 'Jeong, Sunjoo']",PLoS One,,,True
479ad8e93a163df14be1cfbba80b448394298b5c,PMC,Structural genomics of infectious disease drug targets: the SSGCID,http://dx.doi.org/10.1107/S1744309111029204,PMC3169389,21904037,CC BY,"The Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium of researchers at Seattle BioMed, Emerald BioStructures, the University of Washington and Pacific Northwest National Laboratory that was established to apply structural genomics approaches to drug targets from infectious disease organisms. The SSGCID is currently funded over a five-year period by the National Institute of Allergy and Infectious Diseases (NIAID) to determine the three-dimensional structures of 400 proteins from a variety of Category A, B and C pathogens. Target selection engages the infectious disease research and drug-therapy communities to identify drug targets, essential enzymes, virulence factors and vaccine candidates of biomedical relevance to combat infectious diseases. The protein-expression systems, purified proteins, ligand screens and three-dimensional structures produced by SSGCID constitute a valuable resource for drug-discovery research, all of which is made freely available to the greater scientific community. This issue of Acta Crystallographica Section F, entirely devoted to the work of the SSGCID, covers the details of the high-throughput pipeline and presents a series of structures from a broad array of pathogenic organisms. Here, a background is provided on the structural genomics of infectious disease, the essential components of the SSGCID pipeline are discussed and a survey of progress to date is presented.",2011 Aug 13,"['Stacy, Robin', 'Begley, Darren W.', 'Phan, Isabelle', 'Staker, Bart L.', 'Van Voorhis, Wesley C.', 'Varani, Gabriele', 'Buchko, Garry W.', 'Stewart, Lance J.', 'Myler, Peter J.']",Acta Crystallogr Sect F Struct Biol Cryst Commun,,,False
89ac1ba1b647165fe0cf9cefd3dc65df8c162749,PMC,Glycyrrhizin as antiviral agent against Hepatitis C Virus,http://dx.doi.org/10.1186/1479-5876-9-112,PMC3169469,21762538,CC BY,"BACKGROUND: Hepatitis C virus is a major cause of chronic liver diseases which can lead to permanent liver damage, hepatocellular carcinoma and death. The presently available treatment with interferon plus ribavirin, has limited benefits due to adverse side effects such as anemia, depression, fatigue, and ""flu-like"" symptoms. Herbal plants have been used for centuries against different diseases including viral diseases and have become a major source of new compounds to treat bacterial and viral diseases. MATERIAL: The present study was design to study the antiviral effect of Glycyrrhizin (GL) against HCV. For this purpose, HCV infected liver cells were treated with GL at non toxic doses and HCV titer was measured by Quantitative real time RT-PCR. RESULTS AND DISCUSSION: Our results demonstrated that GL inhibit HCV titer in a dose dependent manner and resulted in 50% reduction of HCV at a concentration of 14 ± 2 μg. Comparative studies were made with interferon alpha to investigate synergistic effects, if any, between antiviral compound and interferon alpha 2a. Our data showed that GL exhibited synergistic effect when combined with interferon. Moreover, these results were verified by transiently transfecting the liver cells with HCV 3a core plasmid. The results proved that GL dose dependently inhibit the expression of HCV 3a core gene both at mRNA and protein levels while the GAPDH remained constant. CONCLUSION: Our results suggest that GL inhibit HCV full length viral particles and HCV core gene expression or function in a dose dependent manner and had synergistic effect with interferon. In future, GL along with interferon will be better option to treat HCV infection.",2011 Jul 18,"['Ashfaq, Usman A', 'Masoud, Muhammad S', 'Nawaz, Zafar', 'Riazuddin, Sheikh']",J Transl Med,,,True
a27cb38e8670f317f707a16661115a42b5b1b9fe,PMC,Proteome analysis of vaccinia virus IHD-W-infected HEK 293 cells with 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS of on solid phase support N-terminally sulfonated peptides,http://dx.doi.org/10.1186/1743-422X-8-380,PMC3169512,21806805,CC BY,"BACKGROUND: Despite the successful eradication of smallpox by the WHO-led vaccination programme, pox virus infections remain a considerable health threat. The possible use of smallpox as a bioterrorism agent as well as the continuous occurrence of zoonotic pox virus infections document the relevance to deepen the understanding for virus host interactions. Since the permissiveness of pox infections is independent of hosts surface receptors, but correlates with the ability of the virus to infiltrate the antiviral host response, it directly depends on the hosts proteome set. In this report the proteome of HEK293 cells infected with Vaccinia Virus strain IHD-W was analyzed by 2-dimensional gel electrophoresis and MALDI-PSD-TOF MS in a bottom-up approach. RESULTS: The cellular and viral proteomes of VACV IHD-W infected HEK293 cells, UV-inactivated VACV IHD-W-treated as well as non-infected cells were compared. Derivatization of peptides with 4-sulfophenyl isothiocyanate (SPITC) carried out on ZipTipμ-C18 columns enabled protein identification via the peptides' primary sequence, providing improved s/n ratios as well as signal intensities of the PSD spectra. The expression of more than 24 human proteins was modulated by the viral infection. Effects of UV-inactivated and infectious viruses on the hosts' proteome concerning energy metabolism and proteins associated with gene expression and protein-biosynthesis were quite similar. These effects might therefore be attributed to virus entry and virion proteins. However, the modulation of proteins involved in apoptosis was clearly correlated to infectious viruses. CONCLUSIONS: The proteome analysis of infected cells provides insight into apoptosis modulation, regulation of cellular gene expression and the regulation of energy metabolism. The confidence of protein identifications was clearly improved by the peptides' derivatization with SPITC on a solid phase support. Some of the identified proteins have not been described in the context of poxvirus infections before and need to be further characterised to identify their meaning for apoptosis modulation and pathogenesis.",2011 Aug 1,"['Bartel, Sebastian', 'Doellinger, Joerg', 'Darsow, Kai', 'Bourquain, Daniel', 'Buchholz, Rainer', 'Nitsche, Andreas', 'Lange, Harald A']",Virol J,,,True
6b67761a8689f2744b4046161187a0d128a5d7d1,PMC,"Discovery of the First Insect Nidovirus, a Missing Evolutionary Link in the Emergence of the Largest RNA Virus Genomes",http://dx.doi.org/10.1371/journal.ppat.1002215,PMC3169540,21931546,CC BY,"Nidoviruses with large genomes (26.3–31.7 kb; ‘large nidoviruses’), including Coronaviridae and Roniviridae, are the most complex positive-sense single-stranded RNA (ssRNA+) viruses. Based on genome size, they are far separated from all other ssRNA+ viruses (below 19.6 kb), including the distantly related Arteriviridae (12.7–15.7 kb; ‘small nidoviruses’). Exceptionally for ssRNA+ viruses, large nidoviruses encode a 3′-5′exoribonuclease (ExoN) that was implicated in controlling RNA replication fidelity. Its acquisition may have given rise to the ancestor of large nidoviruses, a hypothesis for which we here provide evolutionary support using comparative genomics involving the newly discovered first insect-borne nidovirus. This Nam Dinh virus (NDiV), named after a Vietnamese province, was isolated from mosquitoes and is yet to be linked to any pathology. The genome of this enveloped 60–80 nm virus is 20,192 nt and has a nidovirus-like polycistronic organization including two large, partially overlapping open reading frames (ORF) 1a and 1b followed by several smaller 3′-proximal ORFs. Peptide sequencing assigned three virion proteins to ORFs 2a, 2b, and 3, which are expressed from two 3′-coterminal subgenomic RNAs. The NDiV ORF1a/ORF1b frameshifting signal and various replicative proteins were tentatively mapped to canonical positions in the nidovirus genome. They include six nidovirus-wide conserved replicase domains, as well as the ExoN and 2′-O-methyltransferase that are specific to large nidoviruses. NDiV ORF1b also encodes a putative N7-methyltransferase, identified in a subset of large nidoviruses, but not the uridylate-specific endonuclease that – in deviation from the current paradigm - is present exclusively in the currently known vertebrate nidoviruses. Rooted phylogenetic inference by Bayesian and Maximum Likelihood methods indicates that NDiV clusters with roniviruses and that its branch diverged from large nidoviruses early after they split from small nidoviruses. Together these characteristics identify NDiV as the prototype of a new nidovirus family and a missing link in the transition from small to large nidoviruses.",2011 Sep 8,"['Nga, Phan Thi', 'Parquet, Maria del Carmen', 'Lauber, Chris', 'Parida, Manmohan', 'Nabeshima, Takeshi', 'Yu, Fuxun', 'Thuy, Nguyen Thanh', 'Inoue, Shingo', 'Ito, Takashi', 'Okamoto, Kenta', 'Ichinose, Akitoyo', 'Snijder, Eric J.', 'Morita, Kouichi', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,True
5bff2f7964b21fc01b102c421814e9ef05b2f2a1,PMC,"Discovery of the First Insect Nidovirus, a Missing Evolutionary Link in the Emergence of the Largest RNA Virus Genomes",http://dx.doi.org/10.1371/journal.ppat.1002215,PMC3169540,21931546,CC BY,"Nidoviruses with large genomes (26.3–31.7 kb; ‘large nidoviruses’), including Coronaviridae and Roniviridae, are the most complex positive-sense single-stranded RNA (ssRNA+) viruses. Based on genome size, they are far separated from all other ssRNA+ viruses (below 19.6 kb), including the distantly related Arteriviridae (12.7–15.7 kb; ‘small nidoviruses’). Exceptionally for ssRNA+ viruses, large nidoviruses encode a 3′-5′exoribonuclease (ExoN) that was implicated in controlling RNA replication fidelity. Its acquisition may have given rise to the ancestor of large nidoviruses, a hypothesis for which we here provide evolutionary support using comparative genomics involving the newly discovered first insect-borne nidovirus. This Nam Dinh virus (NDiV), named after a Vietnamese province, was isolated from mosquitoes and is yet to be linked to any pathology. The genome of this enveloped 60–80 nm virus is 20,192 nt and has a nidovirus-like polycistronic organization including two large, partially overlapping open reading frames (ORF) 1a and 1b followed by several smaller 3′-proximal ORFs. Peptide sequencing assigned three virion proteins to ORFs 2a, 2b, and 3, which are expressed from two 3′-coterminal subgenomic RNAs. The NDiV ORF1a/ORF1b frameshifting signal and various replicative proteins were tentatively mapped to canonical positions in the nidovirus genome. They include six nidovirus-wide conserved replicase domains, as well as the ExoN and 2′-O-methyltransferase that are specific to large nidoviruses. NDiV ORF1b also encodes a putative N7-methyltransferase, identified in a subset of large nidoviruses, but not the uridylate-specific endonuclease that – in deviation from the current paradigm - is present exclusively in the currently known vertebrate nidoviruses. Rooted phylogenetic inference by Bayesian and Maximum Likelihood methods indicates that NDiV clusters with roniviruses and that its branch diverged from large nidoviruses early after they split from small nidoviruses. Together these characteristics identify NDiV as the prototype of a new nidovirus family and a missing link in the transition from small to large nidoviruses.",2011 Sep 8,"['Nga, Phan Thi', 'Parquet, Maria del Carmen', 'Lauber, Chris', 'Parida, Manmohan', 'Nabeshima, Takeshi', 'Yu, Fuxun', 'Thuy, Nguyen Thanh', 'Inoue, Shingo', 'Ito, Takashi', 'Okamoto, Kenta', 'Ichinose, Akitoyo', 'Snijder, Eric J.', 'Morita, Kouichi', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,False
05a0ef8d34e8f046dfb1d2b587fd8653cfab7018,PMC,"Discovery of the First Insect Nidovirus, a Missing Evolutionary Link in the Emergence of the Largest RNA Virus Genomes",http://dx.doi.org/10.1371/journal.ppat.1002215,PMC3169540,21931546,CC BY,"Nidoviruses with large genomes (26.3–31.7 kb; ‘large nidoviruses’), including Coronaviridae and Roniviridae, are the most complex positive-sense single-stranded RNA (ssRNA+) viruses. Based on genome size, they are far separated from all other ssRNA+ viruses (below 19.6 kb), including the distantly related Arteriviridae (12.7–15.7 kb; ‘small nidoviruses’). Exceptionally for ssRNA+ viruses, large nidoviruses encode a 3′-5′exoribonuclease (ExoN) that was implicated in controlling RNA replication fidelity. Its acquisition may have given rise to the ancestor of large nidoviruses, a hypothesis for which we here provide evolutionary support using comparative genomics involving the newly discovered first insect-borne nidovirus. This Nam Dinh virus (NDiV), named after a Vietnamese province, was isolated from mosquitoes and is yet to be linked to any pathology. The genome of this enveloped 60–80 nm virus is 20,192 nt and has a nidovirus-like polycistronic organization including two large, partially overlapping open reading frames (ORF) 1a and 1b followed by several smaller 3′-proximal ORFs. Peptide sequencing assigned three virion proteins to ORFs 2a, 2b, and 3, which are expressed from two 3′-coterminal subgenomic RNAs. The NDiV ORF1a/ORF1b frameshifting signal and various replicative proteins were tentatively mapped to canonical positions in the nidovirus genome. They include six nidovirus-wide conserved replicase domains, as well as the ExoN and 2′-O-methyltransferase that are specific to large nidoviruses. NDiV ORF1b also encodes a putative N7-methyltransferase, identified in a subset of large nidoviruses, but not the uridylate-specific endonuclease that – in deviation from the current paradigm - is present exclusively in the currently known vertebrate nidoviruses. Rooted phylogenetic inference by Bayesian and Maximum Likelihood methods indicates that NDiV clusters with roniviruses and that its branch diverged from large nidoviruses early after they split from small nidoviruses. Together these characteristics identify NDiV as the prototype of a new nidovirus family and a missing link in the transition from small to large nidoviruses.",2011 Sep 8,"['Nga, Phan Thi', 'Parquet, Maria del Carmen', 'Lauber, Chris', 'Parida, Manmohan', 'Nabeshima, Takeshi', 'Yu, Fuxun', 'Thuy, Nguyen Thanh', 'Inoue, Shingo', 'Ito, Takashi', 'Okamoto, Kenta', 'Ichinose, Akitoyo', 'Snijder, Eric J.', 'Morita, Kouichi', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,False
50a09303f9f740ea1b5f3eeaee66dd6bbd49d4f8,PMC,"Discovery of the First Insect Nidovirus, a Missing Evolutionary Link in the Emergence of the Largest RNA Virus Genomes",http://dx.doi.org/10.1371/journal.ppat.1002215,PMC3169540,21931546,CC BY,"Nidoviruses with large genomes (26.3–31.7 kb; ‘large nidoviruses’), including Coronaviridae and Roniviridae, are the most complex positive-sense single-stranded RNA (ssRNA+) viruses. Based on genome size, they are far separated from all other ssRNA+ viruses (below 19.6 kb), including the distantly related Arteriviridae (12.7–15.7 kb; ‘small nidoviruses’). Exceptionally for ssRNA+ viruses, large nidoviruses encode a 3′-5′exoribonuclease (ExoN) that was implicated in controlling RNA replication fidelity. Its acquisition may have given rise to the ancestor of large nidoviruses, a hypothesis for which we here provide evolutionary support using comparative genomics involving the newly discovered first insect-borne nidovirus. This Nam Dinh virus (NDiV), named after a Vietnamese province, was isolated from mosquitoes and is yet to be linked to any pathology. The genome of this enveloped 60–80 nm virus is 20,192 nt and has a nidovirus-like polycistronic organization including two large, partially overlapping open reading frames (ORF) 1a and 1b followed by several smaller 3′-proximal ORFs. Peptide sequencing assigned three virion proteins to ORFs 2a, 2b, and 3, which are expressed from two 3′-coterminal subgenomic RNAs. The NDiV ORF1a/ORF1b frameshifting signal and various replicative proteins were tentatively mapped to canonical positions in the nidovirus genome. They include six nidovirus-wide conserved replicase domains, as well as the ExoN and 2′-O-methyltransferase that are specific to large nidoviruses. NDiV ORF1b also encodes a putative N7-methyltransferase, identified in a subset of large nidoviruses, but not the uridylate-specific endonuclease that – in deviation from the current paradigm - is present exclusively in the currently known vertebrate nidoviruses. Rooted phylogenetic inference by Bayesian and Maximum Likelihood methods indicates that NDiV clusters with roniviruses and that its branch diverged from large nidoviruses early after they split from small nidoviruses. Together these characteristics identify NDiV as the prototype of a new nidovirus family and a missing link in the transition from small to large nidoviruses.",2011 Sep 8,"['Nga, Phan Thi', 'Parquet, Maria del Carmen', 'Lauber, Chris', 'Parida, Manmohan', 'Nabeshima, Takeshi', 'Yu, Fuxun', 'Thuy, Nguyen Thanh', 'Inoue, Shingo', 'Ito, Takashi', 'Okamoto, Kenta', 'Ichinose, Akitoyo', 'Snijder, Eric J.', 'Morita, Kouichi', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,False
7ad4571111757c52a7c4004a6cc1a9e3698a09f4,PMC,Vaccinia Virus Protein C6 Is a Virulence Factor that Binds TBK-1 Adaptor Proteins and Inhibits Activation of IRF3 and IRF7,http://dx.doi.org/10.1371/journal.ppat.1002247,PMC3169548,21931555,CC BY,"Recognition of viruses by pattern recognition receptors (PRRs) causes interferon-β (IFN-β) induction, a key event in the anti-viral innate immune response, and also a target of viral immune evasion. Here the vaccinia virus (VACV) protein C6 is identified as an inhibitor of PRR-induced IFN-β expression by a functional screen of select VACV open reading frames expressed individually in mammalian cells. C6 is a member of a family of Bcl-2-like poxvirus proteins, many of which have been shown to inhibit innate immune signalling pathways. PRRs activate both NF-κB and IFN regulatory factors (IRFs) to activate the IFN-β promoter induction. Data presented here show that C6 inhibits IRF3 activation and translocation into the nucleus, but does not inhibit NF-κB activation. C6 inhibits IRF3 and IRF7 activation downstream of the kinases TANK binding kinase 1 (TBK1) and IκB kinase-ε (IKKε), which phosphorylate and activate these IRFs. However, C6 does not inhibit TBK1- and IKKε-independent IRF7 activation or the induction of promoters by constitutively active forms of IRF3 or IRF7, indicating that C6 acts at the level of the TBK1/IKKε complex. Consistent with this notion, C6 immunoprecipitated with the TBK1 complex scaffold proteins TANK, SINTBAD and NAP1. C6 is expressed early during infection and is present in both nucleus and cytoplasm. Mutant viruses in which the C6L gene is deleted, or mutated so that the C6 protein is not expressed, replicated normally in cell culture but were attenuated in two in vivo models of infection compared to wild type and revertant controls. Thus C6 contributes to VACV virulence and might do so via the inhibition of PRR-induced activation of IRF3 and IRF7.",2011 Sep 8,"['Unterholzner, Leonie', 'Sumner, Rebecca P.', 'Baran, Marcin', 'Ren, Hongwei', 'Mansur, Daniel S.', 'Bourke, Nollaig M.', 'Randow, Felix', 'Smith, Geoffrey L.', 'Bowie, Andrew G.']",PLoS Pathog,,,True
fbf7143172cc18e911174a7ce32856a0a63afc1c,PMC,Self-reported adverse reactions in 4337 healthcare workers immunizations against novel H1N1 influenza,http://dx.doi.org/10.1186/1756-0500-4-297,PMC3170337,21849040,CC BY,"PURPOSE: The use of the 2009 H1N1 vaccine has generated much debate concerning safety issues among the general population and physicians. It was questioned if this is a safe vaccine. Therefore, we investigated the safety of an inactivated monovalent H1N1 pandemic influenza vaccine METHODS: We focused on the H1N1 pandemic influenza vaccine Pandemrix(® )and applied a self reporting questionnaire in a population of healthcare workers (HCWs) and medical students at a major university hospital. RESULTS: In total, 4337 individuals were vaccinated, consisting of 3808 HCWs and 529 medical students. The vaccination rate of the employees was higher than 40%. The majority of individuals were vaccinated in November 2009. In total, 291 of the 4337 vaccinations were reported to lead to one or more adverse reactions (6.7%). Local reactions were reported in 3.8%, myalgia and arthralgia in 3.7%, fatigue in 3.7%, headache in 3.1%. CONCLUSIONS: Our data together with available data from several national and international institutions points to a safe pandemic influenza vaccine.",2011 Aug 17,"['Bias, Harald', 'Quarcoo, David', 'Meier-Wronski, Claus', 'Wicker, Sabine', 'Seybold, Joachim', 'Nienhaus, Albert', 'Groneberg, David A', 'Roux, Andres de']",BMC Res Notes,,,True
8a45b8b7e677272ce3d5d750e943fe6584134a97,PMC,Intracellular Events and Cell Fate in Filovirus Infection,http://dx.doi.org/10.3390/v3081501,PMC3172725,21927676,CC BY,"Marburg and Ebola viruses cause a severe hemorrhagic disease in humans with high fatality rates. Early target cells of filoviruses are monocytes, macrophages, and dendritic cells. The infection spreads to the liver, spleen and later other organs by blood and lymph flow. A hallmark of filovirus infection is the depletion of non-infected lymphocytes; however, the molecular mechanisms leading to the observed bystander lymphocyte apoptosis are poorly understood. Also, there is limited knowledge about the fate of infected cells in filovirus disease. In this review we will explore what is known about the intracellular events leading to virus amplification and cell damage in filovirus infection. Furthermore, we will discuss how cellular dysfunction and cell death may correlate with disease pathogenesis.",2011 Aug 24,"['Olejnik, Judith', 'Ryabchikova, Elena', 'Corley, Ronald B.', 'Mühlberger, Elke']",Viruses,,,True
d7fa2195f292b4bd5cf3bce7670b11c254770923,PMC,Assessment of the Antiviral Properties of Recombinant Porcine SP-D against Various Influenza A Viruses In Vitro,http://dx.doi.org/10.1371/journal.pone.0025005,PMC3173486,21935489,CC BY,"The emergence of influenza viruses resistant to existing classes of antiviral drugs raises concern and there is a need for novel antiviral agents that could be used therapeutically or prophylacticaly. Surfactant protein D (SP-D) belongs to the family of C-type lectins which are important effector molecules of the innate immune system with activity against bacteria and viruses, including influenza viruses. In the present study we evaluated the potential of recombinant porcine SP-D as an antiviral agent against influenza A viruses (IAVs) in vitro. To determine the range of antiviral activity, thirty IAVs of the subtypes H1N1, H3N2 and H5N1 that originated from birds, pigs and humans were selected and tested for their sensitivity to recombinant SP-D. Using these viruses it was shown by hemagglutination inhibition assay, that recombinant porcine SP-D was more potent than recombinant human SP-D and that especially higher order oligomeric forms of SP-D had the strongest antiviral activity. Porcine SP-D was active against a broad range of IAV strains and neutralized a variety of H1N1 and H3N2 IAVs, including 2009 pandemic H1N1 viruses. Using tissue sections of ferret and human trachea, we demonstrated that recombinant porcine SP-D prevented attachment of human seasonal H1N1 and H3N2 virus to receptors on epithelial cells of the upper respiratory tract. It was concluded that recombinant porcine SP-D holds promise as a novel antiviral agent against influenza and further development and evaluation in vivo seems warranted.",2011 Sep 14,"['Hillaire, Marine L. B.', 'van Eijk, Martin', 'van Trierum, Stella E.', 'van Riel, Debby', 'Saelens, Xavier', 'Romijn, Roland A.', 'Hemrika, Wieger', 'Fouchier, Ron A. M.', 'Kuiken, Thijs', 'Osterhaus, Albert D. M. E.', 'Haagsman, Henk P.', 'Rimmelzwaan, Guus F.']",PLoS One,,,True
25615501bc9f54fd01b72047cec1f8ec619b1e69,PMC,Unpolarized Release of Vaccinia Virus and HIV Antigen by Colchicine Treatment Enhances Intranasal HIV Antigen Expression and Mucosal Humoral Responses,http://dx.doi.org/10.1371/journal.pone.0024296,PMC3174162,21935396,CC BY,"The induction of a strong mucosal immune response is essential to building successful HIV vaccines. Highly attenuated recombinant HIV vaccinia virus can be administered mucosally, but even high doses of immunization have been found unable to induce strong mucosal antibody responses. In order to solve this problem, we studied the interactions of recombinant HIV vaccinia virus Tiantan strain (rVTT-gagpol) in mucosal epithelial cells (specifically Caco-2 cell layers) and in BALB/c mice. We evaluated the impact of this virus on HIV antigen delivery and specific immune responses. The results demonstrated that rVTT-gagpol was able to infect Caco-2 cell layers and both the nasal and lung epithelia in BALB/c mice. The progeny viruses and expressed p24 were released mainly from apical surfaces. In BALB/c mice, the infection was limited to the respiratory system and was not observed in the blood. This showed that polarized distribution limited antigen delivery into the whole body and thus limited immune response. To see if this could be improved upon, we stimulated unpolarized budding of the virus and HIV antigens by treating both Caco-2 cells and BALB/c mice with colchicine. We found that, in BALB/c mice, the degree of infection and antigen expression in the epithelia went up. As a result, specific immune responses increased correspondingly. Together, these data suggest that polarized budding limits antigen delivery and immune responses, but unpolarized distribution can increase antigen expression and delivery and thus enhance specific immune responses. This conclusion can be used to optimize mucosal HIV vaccine strategies.",2011 Sep 15,"['Zhang, Yan', 'Yang, Jingyi', 'Bao, Rong', 'Chen, Yaoqing', 'Zhou, Dihan', 'He, Benxia', 'Zhong, Maohua', 'Li, Yaoming', 'Liu, Fang', 'Li, Qiaoli', 'Yang, Yi', 'Han, Chen', 'Sun, Ying', 'Cao, Yuan', 'Yan, Huimin']",PLoS One,,,True
690ab99a21dca381b585a6a7d32f1e5c01f1e52c,PMC,Recurrent Recruitment Manoeuvres Improve Lung Mechanics and Minimize Lung Injury during Mechanical Ventilation of Healthy Mice,http://dx.doi.org/10.1371/journal.pone.0024527,PMC3174196,21935418,CC BY,"INTRODUCTION: Mechanical ventilation (MV) of mice is increasingly required in experimental studies, but the conditions that allow stable ventilation of mice over several hours have not yet been fully defined. In addition, most previous studies documented vital parameters and lung mechanics only incompletely. The aim of the present study was to establish experimental conditions that keep these parameters within their physiological range over a period of 6 h. For this purpose, we also examined the effects of frequent short recruitment manoeuvres (RM) in healthy mice. METHODS: Mice were ventilated at low tidal volume V(T) = 8 mL/kg or high tidal volume V(T) = 16 mL/kg and a positive end-expiratory pressure (PEEP) of 2 or 6 cmH(2)O. RM were performed every 5 min, 60 min or not at all. Lung mechanics were followed by the forced oscillation technique. Blood pressure (BP), electrocardiogram (ECG), heart frequency (HF), oxygen saturation and body temperature were monitored. Blood gases, neutrophil-recruitment, microvascular permeability and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) and blood serum as well as histopathology of the lung were examined. RESULTS: MV with repetitive RM every 5 min resulted in stable respiratory mechanics. Ventilation without RM worsened lung mechanics due to alveolar collapse, leading to impaired gas exchange. HF and BP were affected by anaesthesia, but not by ventilation. Microvascular permeability was highest in atelectatic lungs, whereas neutrophil-recruitment and structural changes were strongest in lungs ventilated with high tidal volume. The cytokines IL-6 and KC, but neither TNF nor IP-10, were elevated in the BAL and serum of all ventilated mice and were reduced by recurrent RM. Lung mechanics, oxygenation and pulmonary inflammation were improved by increased PEEP. CONCLUSIONS: Recurrent RM maintain lung mechanics in their physiological range during low tidal volume ventilation of healthy mice by preventing atelectasis and reduce the development of pulmonary inflammation.",2011 Sep 15,"['Reiss, Lucy Kathleen', 'Kowallik, Anke', 'Uhlig, Stefan']",PLoS One,,,True
54b6c7145a0f7743409d5590780ef253152873dd,PMC,Virtual High-Throughput Screening Identifies Mycophenolic Acid as a Novel RNA Capping Inhibitor,http://dx.doi.org/10.1371/journal.pone.0024806,PMC3174198,21935470,CC BY,"The RNA guanylyltransferase (GTase) is involved in the synthesis of the (m7)Gppp-RNA cap structure found at the 5′ end of eukaryotic mRNAs. GTases are members of the covalent nucleotidyl transferase superfamily, which also includes DNA and RNA ligases. GTases catalyze a two-step reaction in which they initially utilize GTP as a substrate to form a covalent enzyme-GMP intermediate. The GMP moiety is then transferred to the diphosphate end of the RNA transcript in the second step of the reaction to form the Gppp-RNA structure. In the current study, we used a combination of virtual database screening, homology modeling, and biochemical assays to search for novel GTase inhibitors. Using this approach, we demonstrate that mycophenolic acid (MPA) can inhibit the GTase reaction by preventing the catalytic transfer of the GMP moiety onto an acceptor RNA. As such, MPA represents a novel type of inhibitor against RNA guanylyltransferases that inhibits the second step of the catalytic reaction. Moreover, we show that the addition of MPA to S. cerevisiae cells leads to a reduction of capped mRNAs. Finally, biochemical assays also demonstrate that MPA can inhibit DNA ligases through inhibition of the second step of the reaction. The biological implications of these findings for the MPA-mediated inhibition of members of the covalent nucleotidyl superfamily are discussed.",2011 Sep 15,"['Tremblay-Létourneau, Maude', 'Despins, Simon', 'Bougie, Isabelle', 'Bisaillon, Martin']",PLoS One,,,True
3c3f097f19bb3dbbf56eb0f099af81054b305752,PMC,Distinguishing Characteristics between Pandemic 2009–2010 Influenza A (H1N1) and Other Viruses in Patients Hospitalized with Respiratory Illness,http://dx.doi.org/10.1371/journal.pone.0024734,PMC3174965,21949746,CC BY,"BACKGROUND: Differences in clinical presentation and outcomes among patients infected with pandemic 2009 influenza A H1N1 (pH1N1) compared to other respiratory viruses have not been fully elucidated. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study was performed of all hospitalized patients at the peak of the pH1N1 season in whom a single respiratory virus was detected by a molecular assay targeting 18 viruses/subtypes (RVP, Luminex xTAG). Fifty-two percent (615/1192) of patients from October, 2009 to December, 2009 had a single respiratory virus (291 pH1N1; 207 rhinovirus; 45 RSV A/B; 37 parainfluenza; 27 adenovirus; 6 coronavirus; and 2 metapneumovirus). No seasonal influenza A or B was detected. Individuals with pH1N1, compared to other viruses, were more likely to present with fever (92% & 70%), cough (92% & 86%), sore throat (32% & 16%), nausea (31% & 8%), vomiting (39% & 30%), abdominal pain (14% & 7%), and a lower white blood count (8,500/L & 13,600/L, all p-values<0.05). In patients with cough and gastrointestinal complaints, the presence of subjective fever/chills independently raised the likelihood of pH1N1 (OR 10). Fifty-five percent (336/615) of our cohort received antibacterial agents, 63% (385/615) received oseltamivir, and 41% (252/615) received steroids. The mortality rate of our cohort was 1% (7/615) and was higher in individuals with pH1N1 compared to other viruses (2.1% & 0.3%, respectively; p = 0.04). CONCLUSIONS/SIGNIFICANCE: During the peak pandemic 2009–2010 influenza season in Rhode Island, nearly half of patients admitted with influenza-like symptoms had respiratory viruses other than influenza A. A high proportion of patients were treated with antibiotics and pH1N1 infection had higher mortality compared to other respiratory viruses.",2011 Sep 16,"['Chan, Philip A.', 'Mermel, Leonard A.', 'Andrea, Sarah B.', 'McCulloh, Russell', 'Mills, John P.', 'Echenique, Ignacio', 'Leveen, Emily', 'Rybak, Natasha', 'Cunha, Cheston', 'Machan, Jason T.', 'Healey, Terrance T.', 'Chapin, Kimberle C.']",PLoS One,,,True
28b906cb5b5dd66df68bdd155ccc2ab514180c2a,PMC,Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza,http://dx.doi.org/10.1186/1471-2334-11-232,PMC3175217,21880131,CC BY,"BACKGROUND: Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients. METHODS: Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient. RESULTS: Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p < 0.05). Correlation studies demonstrated also the existence of a significant positive association between the levels of these mediators, evidencing that they are simultaneously regulated in response to the virus. CONCLUSIONS: Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1.",2011 Aug 31,"['Almansa, Raquel', 'Anton, Andres', 'Ramirez, Paula', 'Martin-Loeches, Ignacio', 'Banner, David', 'Pumarola, Tomás', 'Xu, Luoling', 'Blanco, Jesús', 'Ran, Longsi', 'Lopez-Campos, Guillermo', 'Martin-Sanchez, Fernando', 'Socias, Lorenzo', 'Loza, Ana', 'Andaluz, David', 'Maravi, Enrique', 'Gordón, Mónica', 'Gallegos, Maria C', 'Fernandez, Victoria', 'León, Cristobal', 'Merino, Pedro', 'Marcos, Maria Ángeles', 'Gandía, Francisco', 'Bobillo, Felipe', 'Resino, Salvador', 'Eiros, Jose Mª', 'Castro, Carmen', 'Mateo, Paula', 'Gonzalez-Rivera, Milagros', 'Rello, Jordi', 'de Lejarazu, Raul Ortiz', 'Kelvin, David J', 'Bermejo-Martin, Jesus F']",BMC Infect Dis,,,True
0c82e4a717a9242e0462b24a8759f98f0c83d677,PMC,Discovery of DNA Viruses in Wild-Caught Mosquitoes Using Small RNA High throughput Sequencing,http://dx.doi.org/10.1371/journal.pone.0024758,PMC3176773,21949749,CC BY,"BACKGROUND: Mosquito-borne infectious diseases pose a severe threat to public health in many areas of the world. Current methods for pathogen detection and surveillance are usually dependent on prior knowledge of the etiologic agents involved. Hence, efficient approaches are required for screening wild mosquito populations to detect known and unknown pathogens. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we explored the use of Next Generation Sequencing to identify viral agents in wild-caught mosquitoes. We extracted total RNA from different mosquito species from South China. Small 18–30 bp length RNA molecules were purified, reverse-transcribed into cDNA and sequenced using Illumina GAIIx instrumentation. Bioinformatic analyses to identify putative viral agents were conducted and the results confirmed by PCR. We identified a non-enveloped single-stranded DNA densovirus in the wild-caught Culex pipiens molestus mosquitoes. The majority of the viral transcripts (.>80% of the region) were covered by the small viral RNAs, with a few peaks of very high coverage obtained. The +/− strand sequence ratio of the small RNAs was approximately 7∶1, indicating that the molecules were mainly derived from the viral RNA transcripts. The small viral RNAs overlapped, enabling contig assembly of the viral genome sequence. We identified some small RNAs in the reverse repeat regions of the viral 5′- and 3′ -untranslated regions where no transcripts were expected. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate for the first time that high throughput sequencing of small RNA is feasible for identifying viral agents in wild-caught mosquitoes. Our results show that it is possible to detect DNA viruses by sequencing the small RNAs obtained from insects, although the underlying mechanism of small viral RNA biogenesis is unclear. Our data and those of other researchers show that high throughput small RNA sequencing can be used for pathogen surveillance in wild mosquito vectors.",2011 Sep 20,"['Ma, Maijuan', 'Huang, Yong', 'Gong, Zhengda', 'Zhuang, Lu', 'Li, Cun', 'Yang, Hong', 'Tong, Yigang', 'Liu, Wei', 'Cao, Wuchun']",PLoS One,,,True
dad72f4c1b14ead806c29f48ce276b06ffeb421a,PMC,Distribution of sialic acid receptors and influenza A virus of avian and swine origin in experimentally infected pigs,http://dx.doi.org/10.1186/1743-422X-8-434,PMC3177912,21902821,CC BY,"BACKGROUND: Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SA-alpha-2,3)) and swine/human (SA-alpha-2,6) influenza viruses in the upper respiratory tract. Furthermore, experimental and natural infections in pigs have been reported with influenza A virus from avian and human sources. METHODS: This study investigated the receptor distribution in the entire respiratory tract of pigs using specific lectins Maackia Amurensis (MAA) I, and II, and Sambucus Nigra (SNA). Furthermore, the predilection sites of swine influenza virus (SIV) subtypes H1N1 and H1N2 as well as avian influenza virus (AIV) subtype H4N6 were investigated in the respiratory tract of experimentally infected pigs using immunohistochemical methods. RESULTS: SIV antigen was widely distributed in bronchi, but was also present in epithelial cells of the nose, trachea, bronchioles, and alveolar type I and II epithelial cells in severely affected animals. AIV was found in the lower respiratory tract, especially in alveolar type II epithelial cells and occasionally in bronchiolar epithelial cells. SA-alpha-2,6 was the predominant receptor in all areas of the respiratory tract with an average of 80-100% lining at the epithelial cells. On the contrary, the SA-alpha-2,3 was not present (0%) at epithelial cells of nose, trachea, and most bronchi, but was found in small amounts in bronchioles, and in alveoli reaching an average of 20-40% at the epithelial cells. Interestingly, the receptor expression of both SA-alpha-2,3 and 2,6 was markedly diminished in influenza infected areas compared to non-infected areas. CONCLUSIONS: A difference in predilection sites between SIV and AIV virus was found, and this difference was in accordance with the distribution of the SA-alpha-2,6 and SA-alpha-2,3 receptor, respectively. The results indicated that the distribution of influenza A virus receptors in pigs are similar to that of humans and therefore challenge the theory that the pig acts as a mixing vessel between human and avian influenza viruses. Furthermore, it was shown that AIV prefers to infect alveolar type II epithelial cells in pigs. This corresponds with findings in humans emphasising the resemblance between the two species.",2011 Sep 8,"['Trebbien, Ramona', 'Larsen, Lars E', 'Viuff, Birgitte M']",Virol J,,,True
52659b7eb39ce3c761658f1f3e5df475cf495919,PMC,Changes in Cytokine Levels and NK Cell Activation Associated with Influenza,http://dx.doi.org/10.1371/journal.pone.0025060,PMC3179484,21966414,CC BY,"Several studies have highlighted the important role played by murine natural killer (NK) cells in the control of influenza infection. However, human NK cell responses in acute influenza infection, including infection with the 2009 pandemic H1N1 influenza virus, are poorly documented. Here, we examined changes in NK cell phenotype and function and plasma cytokine levels associated with influenza infection and vaccination. We show that absolute numbers of peripheral blood NK cells, and particularly those of CD56(bright) NK cells, decreased upon acute influenza infection while this NK cell subset expanded following intramuscular influenza vaccination. NK cells exposed to influenza antigens were activated, with higher proportions of NK cells expressing CD69 in study subjects infected with seasonal influenza strains. Vaccination led to increased levels of CD25+ NK cells, and notably CD56(bright) CD25+ NK cells, whereas decreased amounts of this subset were present in the peripheral blood of influenza infected individuals, and predominantly in study subjects infected with the 2009 pandemic H1N1 influenza virus. Finally, acute influenza infection was associated with low plasma concentrations of inflammatory cytokines, including IFN-γ, MIP-1β, IL-2 and IL-15, and high levels of the anti-inflammatory cytokines IL-10 and IL-1ra. Altogether, these data suggest a role for the CD56(bright) NK cell subset in the response to influenza, potentially involving their recruitment to infected tissues and a local production and/or uptake of inflammatory cytokines.",2011 Sep 23,"['Jost, Stephanie', 'Quillay, Heloise', 'Reardon, Jeff', 'Peterson, Eric', 'Simmons, Rachel P.', 'Parry, Blair A.', 'Bryant, Nancy N. P.', 'Binder, William D.', 'Altfeld, Marcus']",PLoS One,,,True
2df184bde7ca6083d8a33a2b1ce05e302685dc72,PMC,Hepatitis E Virus ORF2 Protein Activates the Pro-Apoptotic Gene CHOP and Anti-Apoptotic Heat Shock Proteins,http://dx.doi.org/10.1371/journal.pone.0025378,PMC3179511,21966512,CC BY,"BACKGROUND: Hepatitis E virus (HEV) is a non-enveloped plus-strand RNA virus that causes acute hepatitis. The capsid protein open reading frame 2 (ORF2) is known to induce endoplasmic reticulum stress in ORF2 expressing cells. METHODOLOGY/PRINCIPAL FINDINGS: In this study we found that HEV ORF2 activates the expression of the pro-apoptotic gene C/EBP homologous protein (CHOP). ORF2 stimulates the CHOP promoter mainly through AARE (amino acid response elements) and to a minor extent the ERSE (endoplasmic reticulum stress response elements). Activating transcription factor 4 (ATF4) protein binds and activates the AARE regulatory sites of the CHOP promoter. ORF2 expression also leads to increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) that in turn initiates the translation of ATF4 mRNA. The pro-apoptotic gene CHOP is an important trigger to initiate endoplasmic reticulum stress induced apoptosis. However, the activation of CHOP by ORF2 in this study did not induce apoptosis, nor did BCL2-associated X protein (Bax) translocate to mitochondria. Microarray analysis revealed an ORF2 specific increased expression of chaperones Hsp72, Hsp70B', and co-chaperone Hsp40. Co-immunoprecipitation (Co-IP) and in silico molecular docking analysis suggests that HEV ORF2 interacts with Hsp72. In addition, Hsp72 shows nuclear accumulation in ORF2 expressing cells. CONCLUSIONS/SIGNIFICANCE: These data provide new insight into simultaneously occurring counter-acting effects of HEV ORF2 that may be part of a strategy to prevent host suicide before completion of the viral replication cycle.",2011 Sep 23,"['John, Lijo', 'Thomas, Saijo', 'Herchenröder, Ottmar', 'Pützer, Brigitte M.', 'Schaefer, Stephan']",PLoS One,,,True
d1d1a8d96a13afa9c54ff26241095b55c0be7ff1,PMC,Chikungunya triggers an autophagic process which promotes viral replication,http://dx.doi.org/10.1186/1743-422X-8-432,PMC3179960,21902836,CC BY,"BACKGROUND: Chikungunya Virus (ChikV) surprised by a massive re-emerging outbreak in Indian Ocean in 2006, reaching Europe in 2007 and exhibited exceptional severe physiopathology in infants and elderly patients. In this context, it is important to analyze the innate immune host responses triggered against ChikV. Autophagy has been shown to be an important component of the innate immune response and is involved in host defense elimination of different pathogens. However, the autophagic process was recently observed to be hijacked by virus for their own replication. Here we provide the first evidence that hallmarks of autophagy are specifically found in HEK.293 infected cells and are involved in ChikV replication. METHODS: To test the capacity of ChikV to mobilize the autophagic machinery, we performed fluorescence microscopy experiments on HEK.GFP.LC3 stable cells, and followed the LC3 distribution during the time course of ChikV infection. To confirm this, we performed electron microscopy on HEK.293 infected cells. To test the effect of ChikV-induced-autophagy on viral replication, we blocked the autophagic process, either by pharmacological (3-MA) or genetic inhibition (siRNA against the transcript of Beclin 1, an autophagic protein), and analyzed the percentage of infected cells and the viral RNA load released in the supernatant. Moreover, the effect of induction of autophagy by Rapamycin on viral replication was tested. RESULTS: The increasing number of GFP-LC3 positive cells with a punctate staining together with the enhanced number of GFP-LC3 dots per cell showed that ChikV triggered an autophagic process in HEK.293 infected cells. Those results were confirmed by electron microscopy analysis since numerous membrane-bound vacuoles characteristic of autophagosomes were observed in infected cells. Moreover, we found that inhibition of autophagy, either by biochemical reagent and RNA interference, dramatically decreases ChikV replication. CONCLUSIONS: Taken together, our results suggest that autophagy may play a promoting role in ChikV replication. Investigating in details the relationship between autophagy and viral replication will greatly improve our knowledge of the pathogenesis of ChikV and provide insight for the design of candidate antiviral therapeutics.",2011 Sep 8,"['Krejbich-Trotot, Pascale', 'Gay, Bernard', 'Li-Pat-Yuen, Ghislaine', 'Hoarau, Jean-Jacques', 'Jaffar-Bandjee, Marie-Christine', 'Briant, Laurence', 'Gasque, Philippe', 'Denizot, Mélanie']",Virol J,,,True
264e7bc2caec36fca2b89d1f21198b8abb4a2d3e,PMC,Leukocyte- and Platelet-Derived Microvesicle Interactions following In Vitro and In Vivo Activation of Toll-Like Receptor 4 by Lipopolysaccharide,http://dx.doi.org/10.1371/journal.pone.0025504,PMC3180459,21966536,CC BY,"BACKGROUND: Pro-coagulant membrane microvesicles (MV) derived from platelets and leukocytes are shed into the circulation following receptor-mediated activation, cell-cell interaction, and apoptosis. Platelets are sentinel markers of toll-like receptor 4 (TLR4) activation. Experiments were designed to evaluate the time course and mechanism of direct interactions between platelets and leukocytes following acute activation of TLR4 by bacterial lipopolysaccharide (LPS). METHODOLOGY/PRINCIPAL FINDINGS: Blood from age-matched male and female wild type (WT) and TLR4 gene deleted (dTLR4) mice was incubated with ultra-pure E. coli LPS (500 ng/ml) for up to one hour. At designated periods, leukocyte antigen positive platelets, platelet antigen positive leukocytes and cell-derived MV were quantified by flow cytometry. Numbers of platelet- or leukocyte-derived MV did not increase within one hour following in vitro exposure of blood to LPS. However, with LPS stimulation numbers of platelets staining positive for both platelet- and leukocyte-specific antigens increased in blood derived from WT but not dTLR4 mice. This effect was blocked by inhibition of TLR4 signaling mediated by My88 and TRIF. Seven days after a single intravenous injection of LPS (500 ng/mouse or 20 ng/gm body wt) to WT mice, none of the platelets stained for leukocyte antigen. However, granulocytes, monocytes and apoptotic bodies stained positive for platelet antigens. CONCLUSIONS/SIGNIFICANCE: Within one hour of exposure to LPS, leukocytes exchange surface antigens with platelets through TLR4 activation. In vivo, leukocyte expression of platelet antigen is retained after a single exposure to LPS following turn over of the platelet pool. Acute expression of leukocyte antigen on platelets within one hour of exposure to LPS and the sustained expression of platelet antigen on leukocytes following a single acute exposure to LPS in vivo explains, in part, associations of platelets and leukocytes in response to bacterial infection and changes in thrombotic propensity of the blood.",2011 Sep 26,"['Xiong, Jing', 'Miller, Virginia M.', 'Hunter, Larry W.', 'Li, Yunman', 'Jayachandran, Muthuvel']",PLoS One,,,True
d336ffee34085032c158363c77b69204c58ca85a,PMC,"Type III IFN Receptor Expression and Functional Characterisation in the Pteropid Bat, Pteropus alecto",http://dx.doi.org/10.1371/journal.pone.0025385,PMC3181264,21980438,CC BY,"Bats are rich reservoir hosts for a variety of viruses, many of which are capable of spillover to other susceptible mammals with lethal consequences. The ability of bats to remain asymptomatic to viral infection may be due to the rapid control of viral replication very early in the immune response through innate antiviral mechanisms. Type I and III interferons (IFNs) represent the first line of defence against viral infection in mammals, with both families of IFNs present in pteropid bats. To obtain further insight into the type III IFN system in bats, we describe the characterization of the type III IFN receptor (IFNλR) in the black flying fox, P. alecto with the characterization of IFNλR1 and IL10R2 genes that make up the type III IFN receptor complex. The bat IFNλR complex has a wide tissue distribution and at the cellular level, both epithelial and immune cells are responsive to IFN-λ treatment. Furthermore, we demonstrate that the bat IFNλR1 chain acts as a functional receptor. To our knowledge, this report represents the first description of an IFN receptor in any species of bat. The responsiveness of bat cells to IFN-λ support a role for the type III IFN system by epithelial and immune cells in bats.",2011 Sep 27,"['Zhou, Peng', 'Cowled, Chris', 'Marsh, Glenn A.', 'Shi, Zhengli', 'Wang, Lin-Fa', 'Baker, Michelle L.']",PLoS One,,,True
579c99c1f830a59ff493ef9a08875f2e4ae2c405,PMC,Discovery and Genomic Characterization of a Novel Ovine Partetravirus and a New Genotype of Bovine Partetravirus,http://dx.doi.org/10.1371/journal.pone.0025619,PMC3181347,21980506,CC BY,"Partetravirus is a recently described group of animal parvoviruses which include the human partetravirus, bovine partetravirus and porcine partetravirus (previously known as human parvovirus 4, bovine hokovirus and porcine hokovirus respectively). In this report, we describe the discovery and genomic characterization of partetraviruses in bovine and ovine samples from China. These partetraviruses were detected by PCR in 1.8% of bovine liver samples, 66.7% of ovine liver samples and 71.4% of ovine spleen samples. One of the bovine partetraviruses detected in the present samples is phylogenetically distinct from previously reported bovine partetraviruses and likely represents a novel genotype. The ovine partetravirus is a novel partetravirus and phylogenetically most related to the bovine partetraviruses. The genome organization is conserved amongst these viruses, including the presence of a putative transmembrane protein encoded by an overlapping reading frame in ORF2. Results from the present study provide further support to the classification of partetraviruses as a separate genus in Parvovirinae.",2011 Sep 27,"['Tse, Herman', 'Tsoi, Hoi-Wah', 'Teng, Jade L. L.', 'Chen, Xin-Chun', 'Liu, Haiying', 'Zhou, Boping', 'Zheng, Bo-Jian', 'Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Yuen, Kwok-Yung']",PLoS One,,,True
4b22e5535c1084bdf92e00eea6bf4e6bd9e246a7,PMC,Discovery and Genomic Characterization of a Novel Ovine Partetravirus and a New Genotype of Bovine Partetravirus,http://dx.doi.org/10.1371/journal.pone.0025619,PMC3181347,21980506,CC BY,"Partetravirus is a recently described group of animal parvoviruses which include the human partetravirus, bovine partetravirus and porcine partetravirus (previously known as human parvovirus 4, bovine hokovirus and porcine hokovirus respectively). In this report, we describe the discovery and genomic characterization of partetraviruses in bovine and ovine samples from China. These partetraviruses were detected by PCR in 1.8% of bovine liver samples, 66.7% of ovine liver samples and 71.4% of ovine spleen samples. One of the bovine partetraviruses detected in the present samples is phylogenetically distinct from previously reported bovine partetraviruses and likely represents a novel genotype. The ovine partetravirus is a novel partetravirus and phylogenetically most related to the bovine partetraviruses. The genome organization is conserved amongst these viruses, including the presence of a putative transmembrane protein encoded by an overlapping reading frame in ORF2. Results from the present study provide further support to the classification of partetraviruses as a separate genus in Parvovirinae.",2011 Sep 27,"['Tse, Herman', 'Tsoi, Hoi-Wah', 'Teng, Jade L. L.', 'Chen, Xin-Chun', 'Liu, Haiying', 'Zhou, Boping', 'Zheng, Bo-Jian', 'Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Yuen, Kwok-Yung']",PLoS One,,,False
f5dc4bad737644cb25aeb8e23ba999402b0df872,PMC,Calf health from birth to weaning. II. Management of diarrhoea in pre-weaned calves,http://dx.doi.org/10.1186/2046-0481-64-9,PMC3182126,21917151,CC BY,"Calfhood diseases have a major impact on the economic viability of cattle operations. The second of this three part review series considers the management of diarrhoeic diseases in pre-weaned calves. In neonatal calf diarrhoea, oral rehydration therapy is the single most important therapeutic measure to be carried out by the farmer and is usually successful if instigated immediately after diarrhoea has developed. Continued feeding of milk or milk replacer to diarrhoeic calves is important, to prevent malnourishment and weight loss in affected calves. Indiscriminative antibiotic treatment of uncomplicated diarrhoea is discouraged, whereas systemically ill calves can benefit from systemic antibiotic treatment for the prevention of septicaemia or concurrent diseases. Ancillary treatments and specific preventive measures are discussed. Eimeriosis has a high economic impact on the farming industries due to direct cost of treatment and calf losses, but especially due to decreased performance of clinically as well as sub-clinically affected animals. Emphasis lies on prophylactic or metaphylactic treatment, since the degree of damage to the intestinal mucosa once diarrhoea has developed, makes therapeutic intervention unrewarding.",2011 Sep 14,"['Lorenz, Ingrid', 'Fagan, John', 'More, Simon J']",Ir Vet J,,,True
ee6d70a53e3262cea6f85bd8b226f6b4c8b5f64b,PMC,"Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009",http://dx.doi.org/10.1371/journal.pone.0025738,PMC3183080,21980532,CC BY,"BACKGROUND: To date, there is little information that reflects the true extent of spread of the pH1N1/2009v influenza pandemic at the community level as infection often results in mild or no clinical symptoms. This study aimed at assessing through a prospective study, the attack rate of pH1N1/2009 virus in Reunion Island and risk factors of infection, during the 2009 season. METHODOLOGY/PRINCIPAL FINDINGS: A serosurvey was conducted during the 2009 austral winter, in the frame of a prospective population study. Pairs of sera were collected from 1687 individuals belonging to 772 households, during and after passage of the pandemic wave. Antibodies to pH1N1/2009v were titered using the hemagglutination inhibition assay (HIA) with titers ≥1/40 being considered positive. Seroprevalence during the first two weeks of detection of pH1N1/2009v in Reunion Island was 29.8% in people under 20 years of age, 35.6% in adults (20–59 years) and 73.3% in the elderly (≥60 years) (P<0.0001). Baseline corrected cumulative incidence rates, were 42.9%, 13.9% and 0% in these age groups respectively (P<0.0001). A significant decline in antibody titers occurred soon after the passage of the epidemic wave. Seroconversion rates to pH1N1/2009 correlated negatively with age: 63.2%, 39.4% and 16.7%, in each age group respectively (P<0.0001). Seroconversion occurred in 65.2% of individuals who were seronegative at inclusion compared to 6.8% in those who were initially seropositive. CONCLUSIONS: Seroincidence of pH1N1/2009v infection was three times that estimated from clinical surveillance, indicating that almost two thirds of infections occurring at the community level have escaped medical detection. People under 20 years of age were the most affected group. Pre-epidemic titers ≥1/40 prevented seroconversion and are likely protective against infection. A concern was raised about the long term stability of the antibody responses.",2011 Sep 29,"['Dellagi, Koussay', 'Rollot, Olivier', 'Temmam, Sarah', 'Salez, Nicolas', 'Guernier, Vanina', 'Pascalis, Hervé', 'Gérardin, Patrick', 'Fianu, Adrian', 'Lapidus, Nathanael', 'Naty, Nadège', 'Tortosa, Pablo', 'Boussaïd, Karim', 'Jaffar-Banjee, Marie-Christine', 'Filleul, Laurent', 'Flahault, Antoine', 'Carrat, Fabrice', 'Favier, Francois', 'de Lamballerie, Xavier']",PLoS One,,,True
7902723eb8b21baa5eef8703832de11cc242a43b,PMC,The sialic acid binding activity of the S protein facilitates infection by porcine transmissible gastroenteritis coronavirus,http://dx.doi.org/10.1186/1743-422X-8-435,PMC3184106,21910859,CC BY,"BACKGROUND: Transmissible gastroenteritis virus (TGEV) has a sialic acid binding activity that is believed to be important for enteropathogenicity, but that has so far appeared to be dispensable for infection of cultured cells. The aims of this study were to determine the effect of sialic acid binding for the infection of cultured cells under unfavorable conditions, and comparison of TGEV strains and mutants, as well as the avian coronavirus IBV concerning their dependence on the sialic acid binding activity. METHODS: The infectivity of different viruses was analyzed by a plaque assay after adsorption times of 5, 20, and 60 min. Prior to infection, cultured cells were either treated with neuraminidase to deplete sialic acids from the cell surface, or mock-treated. In a second approach, pre-treatment of the virus with porcine intestinal mucin was performed, followed by the plaque assay after a 5 min adsorption time. A student's t-test was used to verify the significance of the results. RESULTS: Desialylation of cells only had a minor effect on the infection by TGEV strain Purdue 46 when an adsorption period of 60 min was allowed for initiation of infection. However, when the adsorption time was reduced to 5 min the infectivity on desialylated cells decreased by more than 60%. A TGEV PUR46 mutant (HAD3) deficient in sialic acid binding showed a 77% lower titer than the parental virus after a 5 min adsorption time. After an adsorption time of 60 min the titer of HAD3 was 58% lower than that of TGEV PUR46. Another TGEV strain, TGEV Miller, and IBV Beaudette showed a reduction in infectivity after neuraminidase treatment of the cultured cells irrespective of the virion adsorption time. CONCLUSIONS: Our results suggest that the sialic acid binding activity facilitates the infection by TGEV under unfavorable environmental conditions. The dependence on the sialic acid binding activity for an efficient infection differs in the analyzed TGEV strains.",2011 Sep 12,"['Schwegmann-Weßels, Christel', 'Bauer, Sandra', 'Winter, Christine', 'Enjuanes, Luis', 'Laude, Hubert', 'Herrler, Georg']",Virol J,,,True
626109d4ae81ef0adea376ed72148cdf4e578ac9,PMC,"Welcome to Viruses: A New Open-Access, Multidisciplinary Forum for Virology",http://dx.doi.org/10.3390/v1010001,PMC3185460,21994533,CC BY,,2009 Apr 1,"Freed, Eric O.",Viruses,,,False
3edea664551396420ae233d6951c3a8a71c2870e,PMC,Human Bocavirus – Insights into a Newly Identified Respiratory Virus,http://dx.doi.org/10.3390/v1010003,PMC3185462,21994534,CC BY,"Human Bocavirus (HBoV) was discovered in 2005 using a molecular virus screening technique. It is often found in respiratory samples and is a likely cause for respiratory diseases in children. HBoV is distributed worldwide and has been found not only in respiratory samples, but also in feces, urine and serum. HBoV infections are mostly found in young children and coinfections with other respiratory viruses are often found, exacerbating the efforts to link HBoV to specific symptoms. The purpose of this review is to give an overview of recent HBoV research, highlighting some recent findings.",2009 Apr 21,"['Lüsebrink, Jessica', 'Wittleben, Felix', 'Schildgen, Verena', 'Schildgen, Oliver']",Viruses,,,True
d7ccfdff2703c29904f679dc26fc8fd3f162e402,PMC,An Economical Tandem Multiplex Real-Time PCR Technique for the Detection of a Comprehensive Range of Respiratory Pathogens,http://dx.doi.org/10.3390/v1010042,PMC3185464,21994537,CC BY,"This study used real-time PCR assays to screen small sample volumes for a comprehensive range of 35 respiratory pathogens. Initial thermocycling was limited to 20 cycles to avoid competition for reagents, followed by a secondary real-time multiplex PCR. Supplementary semi-nested human metapneumovirus and picornavirus PCR assays were required to complete the acute respiratory pathogen profile. Potential pathogens were detected in 85 (70%) of pernasal aspirates collected from 121 children with acute respiratory symptoms. Multiple pathogens were detected in 29 (24%) of those samples. The tandem multiplex real-time PCR was an efficient method for the rapid detection of multiple pathogens.",2009 Jun 8,"['Chidlow, Glenys R.', 'Harnett, Gerry B.', 'Shellam, Geoffrey R.', 'Smith, David W.']",Viruses,,,True
27b4bbbc97d4660bbfef9e12bf3c3b9790df9014,PMC,More and More Coronaviruses: Human Coronavirus HKU1,http://dx.doi.org/10.3390/v1010057,PMC3185465,21994538,CC BY,"After human coronaviruses OC43, 229E and NL63, human coronavirus HKU1 (HCoV-HKU1) is the fourth human coronavirus discovered. HCoV-HKU1 is a group 2a coronavirus that is still not cultivable. The G + C contents of HCoV-HKU1 genomes are 32%, the lowest among all known coronaviruses with complete genome sequences available. Among all coronaviruses, HCoV-HKU1 shows the most extreme codon usage bias, attributed most importantly to severe cytosine deamination. All HCoV-HKU1 genomes contain unique tandem copies of a 30-base acidic tandem repeat of unknown function at the N-terminus of nsp3 inside the acidic domain upstream of papain-like protease 1. Three genotypes, A, B and C, of HCoV-HKU1 and homologous recombination among their genomes, are observed. The incidence of HCoV-HKU1 infections is the highest in winter. Similar to other human coronaviruses, HCoV-HKU1 infections have been reported globally, with a median (range) incidence of 0.9 (0 – 4.4) %. HCoV-HKU1 is associated with both upper and lower respiratory tract infections that are mostly self-limiting. The most common method for diagnosing HCoV-HKU1 infection is RT-PCR or real-time RT-PCR using RNA extracted from respiratory tract samples such as nasopharyngeal aspirates (NPA). Both the pol and nucleocapsid genes have been used as the targets for amplification. Monoclonal antibodies have been generated for direct antigen detection in NPA. For antibody detection, Escherichia coli BL21 and baculovirus-expressed recombinant nucleocapsid of HCoV-HKU1 have been used for IgG and IgM detection in sera of patients and normal individuals, using Western blot and enzyme-linked immunoassay.",2009 Jun 11,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Yip, Cyril C. Y.', 'Huang, Yi', 'Yuen, Kwok-Yung']",Viruses,,,True
437df56a9488ff2c8be3754b2642fb688115a1b5,PMC,Significance of Coronavirus Mutants in Feces and Diseased Tissues of Cats Suffering from Feline Infectious Peritonitis,http://dx.doi.org/10.3390/v1020166,PMC3185486,21994544,CC BY,"The internal FECV→FIPV mutation theory and three of its correlates were tested in four sibs/half-sib kittens, a healthy contact cat, and in four unrelated cats that died of FIP at geographically disparate regions. Coronavirus from feces and extraintestinal FIP lesions from the same cat were always >99% related in accessory and structural gene sequences. SNPs and deletions causing a truncation of the 3c gene product were found in almost all isolates from the diseased tissues of the eight cats suffering from FIP, whereas most, but not all fecal isolates from these same cats had intact 3c genes. Other accessory and structural genes appeared normal in both fecal and lesional viruses. Deliterious mutations in the 3c gene were unique to each cat, indicating that they did not originate in one cat and were subsequently passed horizontally to the others. Compartmentalization of the parental and mutant forms was not absolute; virus of lesional type was sometimes found in feces of affected cats and virus identical to fecal type was occasionally identified in diseased tissues. Although 3c gene mutants in this study were not horizontally transmitted, the parental fecal virus was readily transmitted by contact from a cat that died of FIP to its housemate. There was a high rate of mutability in all structural and accessory genes both within and between cats, leading to minor genetic variants. More than one variant could be identified in both diseased tissues and feces of the same cat. Laboratory cats inoculated with a mixture of two closely related variants from the same FIP cat developed disease from one or the other variant, but not both. Significant genetic drift existed between isolates from geographically distinct regions of the Western US.",2009 Aug 26,"['Pedersen, Niels C.', 'Liu, Hongwei', 'Dodd, Kimberly A.', 'Pesavento, Patricia A.']",Viruses,,,True
d739cf97cba31e655d6c7438b864d94297f59ba3,PMC,Regulation of Innate Immune Responses by Bovine Herpesvirus 1 and Infected Cell Protein 0 (bICP0),http://dx.doi.org/10.3390/v1020255,PMC3185490,21994549,CC BY,"Bovine herpesvirus 1 (BoHV-1) infected cell protein 0 (bICP0) is an important transcriptional regulatory protein that stimulates productive infection. In transient transfection assays, bICP0 also inhibits interferon dependent transcription. bICP0 can induce degradation of interferon stimulatory factor 3 (IRF3), a cellular transcription factor that is crucial for activating beta interferon (IFN-β) promoter activity. Recent studies also concluded that interactions between bICP0 and IRF7 inhibit trans-activation of IFN-β promoter activity. The C3HC4 zinc RING (really important new gene) finger located near the amino terminus of bICP0 is important for all known functions of bICP0. A recombinant virus that contains a single amino acid change in a well conserved cysteine residue of the C3HC4 zinc RING finger of bICP0 grows poorly in cultured cells, and does not reactivate from latency in cattle confirming that the C3HC4 zinc RING finger is crucial for viral growth and pathogenesis. A bICP0 deletion mutant does not induce plaques in permissive cells, but induces autophagy in a cell type dependent manner. In summary, the ability of bICP0 to stimulate productive infection, and repress IFN dependent transcription plays a crucial role in the BoHV-1 infection cycle.",2009 Sep 7,"Jones, Clinton",Viruses,,,True
e1c4d9cdea7ddbf8cad8a101da840b3394c5303b,PMC,Plasmacytoid Dendritic Cells and the Control of Herpesvirus Infections,http://dx.doi.org/10.3390/v1030383,PMC3185500,21994554,CC BY,"Type-I interferons (IFN-I) are cytokines essential for vertebrate antiviral defense, including against herpesviruses. IFN-I have potent direct antiviral activities and also mediate a multiplicity of immunoregulatory functions, which can either promote or dampen antiviral adaptive immune responses. Plasmacytoid dendritic cells (pDCs) are the professional producers of IFN-I in response to many viruses, including all of the herpesviruses tested. There is strong evidence that pDCs could play a major role in the initial orchestration of both innate and adaptive antiviral immune responses. Depending on their activation pattern, pDC responses may be either protective or detrimental to the host. Here, we summarize and discuss current knowledge regarding pDC implication in the physiopathology of mouse and human herpesvirus infections, and we discuss how pDC functions could be manipulated in immunotherapeutic settings to promote health over disease.",2009 Oct 14,"['Baranek, Thomas', 'Zucchini, Nicolas', 'Dalod, Marc']",Viruses,,,True
ec4a332b863ec8c1bbf94d605b17c67acddf0889,PMC,Seroconversion to HCoV-NL63 in Rhesus Macaques,http://dx.doi.org/10.3390/v1030647,PMC3185515,21994563,CC BY,"HCoV-NL63 is a recently identified respiratory virus. Its pathogenesis has not been fully unraveled because an animal model is currently lacking. Here we examined whether rhesus macaques encounter HCoV-NL63 infections during life, by examining the levels of antibodies to HCoV-NL63 in time. The animals were followed for 7 up till 19 years, and in three animals we observed a steep rise in antibodies during follow up, indicative of a natural infection with HCoV-NL63.",2009 Oct 30,"['Dijkman, Ronald', 'Mulder, H. Lie', 'Rumping, Lynne', 'Kraaijvanger, Ilse', 'Deijs, Martin', 'Jebbink, Maarten F.', 'Verschoor, Ernst J.', 'van der Hoek, Lia']",Viruses,,,True
72d4e41eee56e6b1e8b7b361375c2e9160a6da49,PMC,Defective Interfering RNAs: Foes of Viruses and Friends of Virologists,http://dx.doi.org/10.3390/v1030895,PMC3185524,21994575,CC BY,"Defective interfering (DI) RNAs are subviral RNAs produced during multiplication of RNA viruses by the error-prone viral replicase. DI-RNAs are parasitic RNAs that are derived from and associated with the parent virus, taking advantage of viral-coded protein factors for their multiplication. Recent advances in the field of DI RNA biology has led to a greater understanding about generation and evolution of DI-RNAs as well as the mechanism of symptom attenuation. Moreover, DI-RNAs are versatile tools in the hands of virologists and are used as less complex surrogate templates to understand the biology of their helper viruses. The ease of their genetic manipulation has resulted in rapid discoveries on cis-acting RNA replication elements required for replication and recombination. DI-RNAs have been further exploited to discover host factors that modulate Tomato bushy stunt virus replication, as well as viral RNA recombination. This review discusses the current models on generation and evolution of DI-RNAs, the roles of viral and host factors in DI-RNA replication, and the mechanisms of disease attenuation.",2009 Nov 10,"['Pathak, Kunj B.', 'Nagy, Peter D.']",Viruses,,,True
f0d935a0e0f1360bf4166b9db8e4cddf67aa9cd7,PMC,Activation of the Antiviral Kinase PKR and Viral Countermeasures,http://dx.doi.org/10.3390/v1030523,PMC3185532,21994559,CC BY,"The interferon-induced double-stranded (ds)RNA-dependent protein kinase (PKR) limits viral replication by an eIF2α-mediated block of translation. Although many negative-strand RNA viruses activate PKR, the responsible RNAs have long remained elusive, as dsRNA, the canonical activator of PKR, has not been detected in cells infected with such viruses. In this review we focus on the activating RNA molecules of different virus families, in particular the negative-strand RNA viruses. We discuss the recently identified non-canonical activators 5′-triphosphate RNA and the vRNP of influenza virus and give an update on strategies of selected RNA and DNA viruses to prevent activation of PKR.",2009 Oct 27,"['Dauber, Bianca', 'Wolff, Thorsten']",Viruses,,,True
ce07f8b5cfe254e66c5d9f174dd1f3208a459520,PMC,All Known Human Rhinovirus Species Are Present in Sputum Specimens of Military Recruits During Respiratory Infection,http://dx.doi.org/10.3390/v1031178,PMC3185535,21994588,CC BY,"Human rhinoviruses (HRV) are known to cause common cold as well as more complicated respiratory infections. HRV species -A, -B and -C have all been associated with lower respiratory infections and exacerbations of asthma. However, the type distribution of strains connected to different kinds of lower respiratory conditions is not clearly known. We have analysed the presence of HRV in sputum specimens derived from military recruits with and without pre-diagnosed asthma at times of acute respiratory infection (CIAS Study, 2004–2005). The analysis was performed with HRV and HEV real-time RT-PCR assays. Subsequently we studied type distribution of HRV strains by genetic typing in the VP4/VP2 genomic region. In total 146 (38.8%) specimens were HRV-positive and 36 (9.3%) HEV-positive. No difference was found in HRV detection between the asthmatic vs. non-asthmatic patients. Most of the genetically typed strains, 18 (62.1%), belonged to HRV-A, while HRV-B strains constituted five (17.2%) of the HRV-positive strains. HRV-C strain was typed four times from the HRV-positive cases and a HEV-D strain twice. We further typed six HEV positive strains in the partial VP1 region. Three of these belonged to HRV-A and three to HEV-D. HRV-A strains were discovered throughout the study period, while HRV-C strains originated from winter and spring specimens. Interestingly, four out of five typed HRV-B strains originated from the summer season specimens.",2009 Dec 4,"['Savolainen-Kopra, Carita', 'Blomqvist, Soile', 'Kaijalainen, Svetlana', 'Jounio, Ulla', 'Juvonen, Raija', 'Peitso, Ari', 'Saukkoriipi, Annika', 'Vainio, Olli', 'Hovi, Tapani', 'Roivainen, Merja']",Viruses,,,True
7e6fc218bd723f70d305eadff23e036875076250,PMC,WU Polyomavirus (WUPyV): A Recently Detected Virus Causing Respiratory Disease?,http://dx.doi.org/10.3390/v1030678,PMC3185540,21994565,CC BY,"The WU polyomavirus (WUPyV) is a novel member of the family Polyomaviridae recently detected in respiratory tract specimens by shotgun sequencing. Intriguingly, viral genome has been detected in 0.4% to 11.5% of respiratory tract specimens from children with respiratory disease. The levels of co-infection with established respiratory viruses were in the range between 30.8% and 91.7%. Moreover, some studies report detection of WUPyV in stool or serum. So far, WUPyV infections can not be distinguished from other viral infections by means of clinical symptoms. Respiratory tract disease like pneumonia or bronchitis is frequently observed in patients harbouring WUPyV. Detection of viremia suggests systemic infections. However, the available data do not prove WUPyV to be a human pathogen. Further investigations are necessary.",2009 Nov 4,"['Kleines, Michael', 'Häusler, Martin', 'Krüttgen, Alexander', 'Scheithauer, Simone']",Viruses,,,True
789d8f8e801484da5740462f088a39aaf4e2a411,PMC,Maturation Pathways of Cross-Reactive HIV-1 Neutralizing Antibodies,http://dx.doi.org/10.3390/v1030802,PMC3185542,21994570,CC BY,"Several human monoclonal antibodies (hmAbs) and antibody fragments, including the best characterized in terms of structure-function b12 and Fab X5, exhibit relatively potent and broad HIV-1 neutralizing activity. However, the elicitation of b12 or b12-like antibodies in vivo by vaccine immunogens based on the HIV-1 envelope glycoprotein (Env) has not been successful. B12 is highly divergent from the closest corresponding germline antibody while X5 is less divergent. We have hypothesized that the relatively high degree of specific somatic hypermutations may preclude binding of the HIV-1 envelope glycoprotein (Env) to closest germline antibodies, and that identifying antibodies that are intermediates in the pathways to maturation could help design novel vaccine immunogens to guide the immune system for their enhanced elicitation. In support of this hypothesis we have previously found that a germline-like b12 (monovalent and bivalent scFv as an Fc fusion protein or IgG) lacks measurable binding to an Env as measured by ELISA with a sensitivity in the μM range [1]; here we present evidence confirming and expanding these findings for a panel of Envs. In contrast, a germline-like scFv X5 bound Env with high (nM) affinity. To begin to explore the maturation pathways of these antibodies we identified several possible b12 intermediate antibodies and tested their neutralizing activity. These intermediate antibodies neutralized only some HIV-1 isolates and with relatively weak potency. In contrast, germline-like scFv X5 neutralized a subset of the tested HIV-1 isolates with comparable efficiencies to that of the mature X5. These results could help explain the relatively high immunogenicity of the coreceptor binding site on gp120 and the abundance of CD4-induced (CD4i) antibodies in HIV-1-infected patients (X5 is a CD4i antibody) as well as the maturation pathway of X5. They also can help identify antigens that can bind specifically to b12 germline and intermediate antibodies that together with Envs could be used as a conceptually novel type of candidate vaccines. Such candidate vaccines based on two or more immunogens could help guiding the immune system through complex maturation pathways for elicitation of antibodies that are similar or identical to antibodies with known properties.",2009 Nov 6,"['Xiao, Xiaodong', 'Chen, Weizao', 'Feng, Yang', 'Dimitrov, Dimiter S.']",Viruses,,,True
1c8afcb822dac8e8e5b33a85c2c2e9c7cc24a25a,PMC,Complete Nucleotide Analysis of the Structural Genome of the Infectious Bronchitis Virus Strain Md27 Reveals its Mosaic Nature,http://dx.doi.org/10.3390/v1031166,PMC3185546,21994587,CC BY,"Infectious bronchitis virus (IBV) causes highly contagious respiratory or urogenital tract diseases in chickens. The Maryland 27(Md27) strain was first isolated in 1976 from diseased chicken flocks in the Delmarva Peninsula region. To understand the genetic diversity and phylogenetic relationship of existing strains with Md27, the complete nucleotide sequence of the 3′end coding region (∼7.2 kb) of Md27 was determined and compared with other IBV strains and coronaviruses. It has the same S-3-M-5-N-3′ gene order, as is the case of other IBV strains. The spike gene of Md27 exhibits 97% identity with the SE17 strain. There are deletions at the spike gene, non-coding region between M and 5 genes, and at the 3′ untranslated region (UTR), which is different from Ark-like strains. Phylogenetic analysis and sequence alignments demonstrate that Md27 is a chimera containing different gene segments that are most closely related to the SE17, Conn and JMK strains. This current study provides evidence for genomic mutations and intergenic recombination that have taken place in the evolution of IBV strain Md27.",2009 Dec 4,"['Ammayappan, Arun', 'Vakharia, Vikram N.']",Viruses,,,True
ab26098d2e9876c05c8c1fd3d30d45a749b944e3,PMC,The Development of an AIDS Mucosal Vaccine,http://dx.doi.org/10.3390/v2010283,PMC3185548,21994611,CC BY,"It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1), a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, replication and amplification. Since HIV-1 establishes its early replication in vaginal or rectal mucosal tissues, the induction of sufficient mucosal immunity at the initial site of HIV-1 transmission becomes essential for a protective vaccine. However, despite the fact that current conventional vaccine strategies have remained unsuccessful in preventing HIV-1 infection, sufficient financial support and resources have yet to be given to develop a vaccine able to elicit protective mucosal immunity against sexual transmissions. Interestingly, Chinese ancestors invented variolation through intranasal administration about one thousand years ago, which led to the discovery of a successful smallpox vaccine and the final eradication of the disease. It is the hope for all mankind that the development of a mucosal AIDS vaccine will ultimately help control the AIDS pandemic. In order to discover an effective mucosal AIDS vaccine, it is necessary to have a deep understanding of mucosal immunology and to test various mucosal vaccination strategies.",2010 Jan 22,"['Tang, Xian', 'Chen, Zhiwei']",Viruses,,,True
40afe56736a9733a103c22570b574165d7d38edd,PMC,Antiviral Properties of ISG15,http://dx.doi.org/10.3390/v2102154,PMC3185569,21994614,CC BY,"The type I interferon system plays a critical role in limiting the spread of viral infection. Viruses induce the production of interferon (IFN), which after binding to the IFN-α/β receptor (IFNAR), and triggering of the JAK/STAT signaling cascade, results in the induction of interferon-stimulated genes (ISGs). These ISGs function to inhibit viral replication and to regulate the host immune response. Among these ISGs, the ubiquitin-like molecule, ISG15, is one of the most strongly induced proteins. Similar to ubiquitin, through an IFN induced conjugation cascade, ISG15 is covalently linked to a variety of cellular proteins, suggesting regulation of different cellular processes. Studies performed over the past several years have shown that ISG15 plays a central role in the host’s antiviral response against many viruses. Mice lacking ISG15 display increased susceptibility to multiple viruses. Furthermore, several viruses have developed immune evasion strategies that directly target the ISG15 pathway. Work is now underway to determine the mechanism by which ISG15 functions as an antiviral molecule, such that therapies targeting this pathway can be developed in the future.",2010 Sep 28,"Lenschow, Deborah J.",Viruses,,,True
796abc8d89c17b85820bfd4a6466dc9cda531e4b,PMC,Poxvirus Exploitation of the Ubiquitin-Proteasome System,http://dx.doi.org/10.3390/v2102356,PMC3185573,21994622,CC BY,"Ubiquitination plays a critical role in many cellular processes. A growing number of viruses have evolved strategies to exploit the ubiquitin-proteasome system, including members of the Poxviridae family. Members of the poxvirus family have recently been shown to encode BTB/kelch and ankyrin/F-box proteins that interact with cullin-3 and cullin-1 based ubiquitin ligases, respectively. Multiple members of the poxvirus family also encode ubiquitin ligases with intrinsic activity. This review describes the numerous mechanisms that poxviruses employ to manipulate the ubiquitin-proteasome system.",2010 Oct 19,"['Barry, Michele', 'van Buuren, Nicholas', 'Burles, Kristin', 'Mottet, Kelly', 'Wang, Qian', 'Teale, Alastair']",Viruses,,,True
48764be42938595e40cb6c0bc73fc891a6e962e1,PMC,Buying Time—The Immune System Determinants of the Incubation Period to Respiratory Viruses,http://dx.doi.org/10.3390/v2112541,PMC3185581,21994630,CC BY,"Respiratory viruses cause disease in humans characterized by an abrupt onset of symptoms. Studies in humans and animal models have shown that symptoms are not immediate and appear days or even weeks after infection. Since the initial symptoms are a manifestation of virus recognition by elements of the innate immune response, early virus replication must go largely undetected. The interval between infection and the emergence of symptoms is called the incubation period and is widely used as a clinical score. While incubation periods have been described for many virus infections the underlying mechanism for this asymptomatic phase has not been comprehensively documented. Here we review studies of the interaction between human pathogenic respiratory RNA viruses and the host with a particular emphasis on the mechanisms used by viruses to inhibit immunity. We discuss the concept of the “stealth phase”, defined as the time between infection and the earliest detectable inflammatory response. We propose that the “stealth phase” phenomenon is primarily responsible for the suppression of symptoms during the incubation period and results from viral antagonism that inhibits major pathways of the innate immune system allowing an extended time of unhindered virus replication.",2010 Nov 18,"['Hermesh, Tamar', 'Moltedo, Bruno', 'López, Carolina B.', 'Moran, Thomas M.']",Viruses,,,True
81ef62610df1e107053f06e2fa745a33912e299f,PMC,Making of Viral Replication Organelles by Remodeling Interior Membranes,http://dx.doi.org/10.3390/v2112436,PMC3185585,21994625,CC BY,"Positive-stranded RNA (+RNA) viruses exploit host cell machinery by subverting host proteins and membranes and altering cellular pathways during infection. To achieve robust replication, some +RNA viruses, such as poliovirus (PV), build special intracellular compartments, called viral replication organelles. A recent work from the Altan-Bonnett laboratory [1] gave new insights into the formation of poliovirus replication organelles, which are unique subcellular structures containing many individual replication complexes as a result of dynamic cellular membrane remodeling.",2010 Nov 5,"['Sasvari, Zsuzsanna', 'Nagy, Peter D.']",Viruses,,,True
67448222647675616fa788dcf9426cefa3fd9575,PMC,Monkeypox Virus Infections in Small Animal Models for Evaluation of Anti-Poxvirus Agents,http://dx.doi.org/10.3390/v2122763,PMC3185589,21994638,CC BY,"An ideal animal model for the study of a human disease is one which utilizes a route of infection that mimics the natural transmission of the pathogen; the ability to obtain disease with an infectious dose equivalent to that causing disease in humans; as well having a disease course, morbidity and mortality similar to that seen with human disease. Additionally, the animal model should have a mode(s) of transmission that mimics human cases. The development of small animal models for the study of monkeypox virus (MPXV) has been quite extensive for the relatively short period of time this pathogen has been known, although only a few of these models have been used to study anti-poxvirus agents. We will review those MPXV small animal models that have been developed thus far for the study of therapeutic agents.",2010 Dec 20,"['Hutson, Christina L.', 'Damon, Inger K.']",Viruses,,,True
c59f056b663000ffe9a935dbc10fcd847dd67867,PMC,Viral Genomics and Bioinformatics,http://dx.doi.org/10.3390/v2122587,PMC3185590,21994632,CC BY,,2010 Nov 30,"Seto, Donald",Viruses,,,True
efe13a8d42b60ef9f7387ea539a1b2eeb5f80101,PMC,Hantaviruses in the Americas and Their Role as Emerging Pathogens,http://dx.doi.org/10.3390/v2122559,PMC3185593,21994631,CC BY,"The continued emergence and re-emergence of pathogens represent an ongoing, sometimes major, threat to populations. Hantaviruses (family Bunyaviridae) and their associated human diseases were considered to be confined to Eurasia, but the occurrence of an outbreak in 1993–94 in the southwestern United States led to a great increase in their study among virologists worldwide. Well over 40 hantaviral genotypes have been described, the large majority since 1993, and nearly half of them pathogenic for humans. Hantaviruses cause persistent infections in their reservoir hosts, and in the Americas, human disease is manifest as a cardiopulmonary compromise, hantavirus cardiopulmonary syndrome (HCPS), with case-fatality ratios, for the most common viral serotypes, between 30% and 40%. Habitat disturbance and larger-scale ecological disturbances, perhaps including climate change, are among the factors that may have increased the human caseload of HCPS between 1993 and the present. We consider here the features that influence the structure of host population dynamics that may lead to viral outbreaks, as well as the macromolecular determinants of hantaviruses that have been regarded as having potential contribution to pathogenicity.",2010 Nov 25,"['Hjelle, Brian', 'Torres-Pérez, Fernando']",Viruses,,,True
738d255294896f43d6ac7546a891900714ef1d51,PMC,PEGylated Adenoviruses: From Mice to Monkeys,http://dx.doi.org/10.3390/v2020468,PMC3185605,21994645,CC BY,"Covalent modification with polyethylene glycol (PEG), a non-toxic polymer used in food, cosmetic and pharmaceutical preparations for over 60 years, can profoundly influence the pharmacokinetic, pharmacologic and toxciologic profile of protein and peptide-based therapeutics. This review summarizes the history of PEGylation and PEG chemistry and highlights the value of this technology in the context of the design and development of recombinant viruses for gene transfer, vaccination and diagnostic purposes. Specific emphasis is placed on the application of this technology to the adenovirus, the most potent viral vector with the most highly characterized toxicity profile to date, in several animal models.",2010 Feb 1,"['Wonganan, Piyanuch', 'Croyle, Maria A.']",Viruses,,,True
00cb1a95986171a256f5ef14701bd8f571221a28,PMC,How Flaviviruses Activate and Suppress the Interferon Response,http://dx.doi.org/10.3390/v2020676,PMC3185611,21994652,CC BY,"The flavivirus genus includes viruses with a remarkable ability to produce disease on a large scale. The expansion and increased endemicity of dengue and West Nile viruses in the Americas exemplifies their medical and epidemiological importance. The rapid detection of viral infection and induction of the innate antiviral response are crucial to determining the outcome of infection. The intracellular pathogen receptors RIG-I and MDA5 play a central role in detecting flavivirus infections and initiating a robust antiviral response. Yet, these viruses are still capable of producing acute illness in humans. It is now clear that flaviviruses utilize a variety of mechanisms to modulate the interferon response. The non-structural proteins of the various flaviviruses reduce expression of interferon dependent genes by blocking phosphorylation, enhancing degradation or down-regulating expression of major components of the JAK/STAT pathway. Recent studies indicate that interferon modulation is an important factor in the development of severe flaviviral illness. This suggests that an increased understanding of viral-host interactions will facilitate the development of novel therapeutics to treat these viral infections and improved biological models to study flavivirus pathogenesis.",2010 Feb 23,"['Muñoz-Jordán, Jorge L.', 'Fredericksen, Brenda L.']",Viruses,,,True
390b508dfbde0fbf9b91e67cc77fcd3bf0e391ed,PMC,An Ecological and Conservation Perspective on Advances in the Applied Virology of Zoonoses,http://dx.doi.org/10.3390/v3040379,PMC3185704,21994738,CC BY,"The aim of this manuscript is to describe how modern advances in our knowledge of viruses and viral evolution can be applied to the fields of disease ecology and conservation. We review recent progress in virology and provide examples of how it is informing both empirical research in field ecology and applied conservation. We include a discussion of needed breakthroughs and ways to bridge communication gaps between the field and the lab. In an effort to foster this interdisciplinary effort, we have also included a table that lists the definitions of key terms. The importance of understanding the dynamics of zoonotic pathogens in their reservoir hosts is emphasized as a tool to both assess risk factors for spillover and to test hypotheses related to treatment and/or intervention strategies. In conclusion, we highlight the need for smart surveillance, viral discovery efforts and predictive modeling. A shift towards a predictive approach is necessary in today’s globalized society because, as the 2009 H1N1 pandemic demonstrated, identification post-emergence is often too late to prevent global spread. Integrating molecular virology and ecological techniques will allow for earlier recognition of potentially dangerous pathogens, ideally before they jump from wildlife reservoirs into human or livestock populations and cause serious public health or conservation issues.",2011 Apr 15,"['Vandegrift, Kurt J.', 'Wale, Nina', 'Epstein, Jonathan H.']",Viruses,,,True
2965d872997d38cdfcde8b9bb17c8c659b0a16f7,PMC,siRNA for Influenza Therapy,http://dx.doi.org/10.3390/v2071448,PMC3185718,21994689,CC BY,"Influenza virus is one of the most prevalent and ancient infections in humans. About a fifth of world’s population is infected by influenza virus annually, leading to high morbidity and mortality, particularly in infants, the elderly and the immunocompromised. In the US alone, influenza outbreaks lead to roughly 30,000 deaths each year. Current vaccines and anti-influenza drugs are of limited use due to high mutation rate of the virus and side effects. In recent years, RNA interference, triggered by synthetic short interfering RNA (siRNA), has rapidly evolved as a potent antiviral regimen. Properly designed siRNAs have been shown to function as potent inhibitors of influenza virus replication. The siRNAs outperform traditional small molecule antivirals in a number of areas, such as ease of design, modest cost, and fast turnaround. Although specificity and tissue delivery remain major bottlenecks in the clinical applications of RNAi in general, intranasal application of siRNA against respiratory viruses including, but not limited to influenza virus, has experienced significant success and optimism, which is reviewed here.",2010 Jul 9,"Barik, Sailen",Viruses,,,True
55f46f193444dd9f891aab9b4320f38d5161f8ba,PMC,Possibilities for RNA Interference in Developing Hepatitis C Virus Therapeutics,http://dx.doi.org/10.3390/v2081647,PMC3185727,21994699,CC BY,"The discovery and characterization of the RNA interference (RNAi) pathway has been one of the most important scientific developments of the last 12 years. RNAi is a cellular pathway wherein small RNAs control the expression of genes by either degrading homologous RNAs or preventing the translation of RNAs with partial homology. It has impacted basic biology on two major fronts. The first is the discovery of microRNAs (miRNAs), which regulate almost every cellular process and are required for some viral infections, including hepatitis C virus (HCV). The second front is the use of small interfering RNAs (siRNAs) as the first robust tool for mammalian cellular genetics. This has led to the identification of hundreds of cellular genes that are important for HCV infection. There is now a major push to adapt RNAi technology to the clinic. In this review, we explore the impact of RNAi in understanding HCV biology, the progress in design of RNAi-based therapeutics for HCV, and remaining obstacles.",2010 Aug 6,"['Berger, Kristi L.', 'Randall, Glenn']",Viruses,,,True
42c4f1b128cea03599c36e89eff62afa7e02caa2,PMC,Coronavirus Genomics and Bioinformatics Analysis,http://dx.doi.org/10.3390/v2081803,PMC3185738,21994708,CC BY,"The drastic increase in the number of coronaviruses discovered and coronavirus genomes being sequenced have given us an unprecedented opportunity to perform genomics and bioinformatics analysis on this family of viruses. Coronaviruses possess the largest genomes (26.4 to 31.7 kb) among all known RNA viruses, with G + C contents varying from 32% to 43%. Variable numbers of small ORFs are present between the various conserved genes (ORF1ab, spike, envelope, membrane and nucleocapsid) and downstream to nucleocapsid gene in different coronavirus lineages. Phylogenetically, three genera, Alphacoronavirus, Betacoronavirus and Gammacoronavirus, with Betacoronavirus consisting of subgroups A, B, C and D, exist. A fourth genus, Deltacoronavirus, which includes bulbul coronavirus HKU11, thrush coronavirus HKU12 and munia coronavirus HKU13, is emerging. Molecular clock analysis using various gene loci revealed that the time of most recent common ancestor of human/civet SARS related coronavirus to be 1999–2002, with estimated substitution rate of 4×10(−4) to 2×10(−2) substitutions per site per year. Recombination in coronaviruses was most notable between different strains of murine hepatitis virus (MHV), between different strains of infectious bronchitis virus, between MHV and bovine coronavirus, between feline coronavirus (FCoV) type I and canine coronavirus generating FCoV type II, and between the three genotypes of human coronavirus HKU1 (HCoV-HKU1). Codon usage bias in coronaviruses were observed, with HCoV-HKU1 showing the most extreme bias, and cytosine deamination and selection of CpG suppressed clones are the two major independent biological forces that shape such codon usage bias in coronaviruses.",2010 Aug 24,"['Woo, Patrick C. Y.', 'Huang, Yi', 'Lau, Susanna K. P.', 'Yuen, Kwok-Yung']",Viruses,,,True
4e1119e030d3d053276c55c9220a388d743bb0e3,PMC,Systems-Biology Approaches to Discover Anti-Viral Effectors of the Human Innate Immune Response,http://dx.doi.org/10.3390/v3071112,PMC3185791,21994773,CC BY,"Virus infections elicit an immediate innate response involving antiviral factors. The activities of some of these factors are, in turn, blocked by viral countermeasures. The ensuing battle between the host and the viruses is crucial for determining whether the virus establishes a foothold and/or induces adaptive immune responses. A comprehensive systems-level understanding of the repertoire of anti-viral effectors in the context of these immediate virus-host responses would provide significant advantages in devising novel strategies to interfere with the initial establishment of infections. Recent efforts to identify cellular factors in a comprehensive and unbiased manner, using genome-wide siRNA screens and other systems biology “omics” methodologies, have revealed several potential anti-viral effectors for viruses like Human immunodeficiency virus type 1 (HIV-1), Hepatitis C virus (HCV), West Nile virus (WNV), and influenza virus. This review describes the discovery of novel viral restriction factors and discusses how the integration of different methods in systems biology can be used to more comprehensively identify the intimate interactions of viruses and the cellular innate resistance.",2011 Jul 11,"['Münk, Carsten', 'Sommer, Andreas F.R.', 'König, Renate']",Viruses,,,True
8b9bec3c317211d347532e8991d2494098d16dc2,PMC,Dengue Virus and Autophagy,http://dx.doi.org/10.3390/v3081332,PMC3185800,21994782,CC BY,"Several independent groups have published that autophagy is required for optimal RNA replication of dengue virus (DENV). Initially, it was postulated that autophagosomes might play a structural role in replication complex formation. However, cryo-EM tomography of DENV replication complexes showed that DENV replicates on endoplasmic reticulum (ER) cisternae invaginations and not on classical autophagosomes. Recently, it was reported that autophagy plays an indirect role in DENV replication by modulating cellular lipid metabolism. DENV-induced autophagosomes deplete cellular triglycerides that are stored in lipid droplets, leading to increased β-oxidation and energy production. This is the first example of a virus triggering autophagy to modulate cellular physiology. In this review, we summarize these data and discuss new questions and implications for autophagy during DENV replication.",2011 Aug 4,"['Heaton, Nicholas S.', 'Randall, Glenn']",Viruses,,,True
29cc49c0a88d00ecc54d45ff5bf9128e47e9a444,PMC,The Prevalence and Significance of HTLV-I/II Seroindeterminate Western Blot Patterns,http://dx.doi.org/10.3390/v3081320,PMC3185804,21994781,CC BY,"Human T-lymphotropic virus type I (HTLV-I) infects an estimated 15–20 million persons worldwide. A number of diseases have been associated with the virus including adult T-cell leukemia (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-I uveitis, and HTLV-I-associated infective dermatitis. Once it was shown that there is an increased risk for developing HAM/TSP associated with blood transfusion, screening for HTLV-1 among blood banks was implemented in Japan, United States, France, and the Netherlands. This process includes detection by an enzyme immunoassay (EIA) followed by a confirmatory Western blot (WB) in which recombinant proteins specific for HTLV-I Env glycoproteins are incorporated into WB strips. HTLV-I seropositive results are defined by the presence of antibodies against either gp46 or gp62/68 (both Env protein bands) and either p19, p24, or p53 (one of the gag bands). HTLV-II seropositivity is confirmed by the presence of rgp46-II. However, numerous cases have been documented in which serum samples are reactive by EIA, but an incomplete banding pattern is displayed by subsequent confirmatory WB. Although the significance of these HTLV-I/II seroindeterminates is unclear, it may suggest a much higher incidence of exposure to HTLV-I/II than previously estimated.",2011 Aug 2,"['Abrams, Anna', 'Akahata, Yoshimi', 'Jacobson, Steven']",Viruses,,,True
120aebc8b074393770c411ebf774ed18a5a2a1da,PMC,Impact of the Autophagy Machinery on Hepatitis C Virus Infection,http://dx.doi.org/10.3390/v3081342,PMC3185811,21994783,CC BY,"Autophagy is a cellular process that catabolizes cytoplasmic components and maintains energy homeostasis. As a stress response, the autophagy machinery interconnects a wide range of cellular pathways, enhancing the spread of certain pathogens while limiting others, and has become a highly active research area over the past several years. Independent laboratories have recently reported that autophagy vesicles accumulate in hepatitis C virus (HCV) infected cells and that autophagy proteins can function as proviral factors required for HCV replication. In this review, we summarize what is currently known about the interplay between autophagy and HCV and the possible mechanisms whereby autophagy proteins might favor HCV propagation.",2011 Aug 4,"['Dreux, Marlène', 'Chisari, Francis V.']",Viruses,,,True
54283f47537cca8cedd424a4097d258dc66a9e7a,PMC,"Communicable Diseases Prioritized for Surveillance and Epidemiological Research: Results of a Standardized Prioritization Procedure in Germany, 2011",http://dx.doi.org/10.1371/journal.pone.0025691,PMC3186774,21991334,CC BY,"INTRODUCTION: To establish strategic priorities for the German national public health institute (RKI) and guide the institute's mid-term strategic decisions, we prioritized infectious pathogens in accordance with their importance for national surveillance and epidemiological research. METHODS: We used the Delphi process with internal (RKI) and external experts and a metric-consensus approach to score pathogens according to ten three-tiered criteria. Additional experts were invited to weight each criterion, leading to the calculation of a median weight by which each score was multiplied. We ranked the pathogens according to the total weighted score and divided them into four priority groups. RESULTS: 127 pathogens were scored. Eighty-six experts participated in the weighting; “Case fatality rate” was rated as the most important criterion. Twenty-six pathogens were ranked in the highest priority group; among those were pathogens with internationally recognised importance (e.g., Human Immunodeficiency Virus, Mycobacterium tuberculosis, Influenza virus, Hepatitis C virus, Neisseria meningitides), pathogens frequently causing large outbreaks (e.g., Campylobacter spp.), and nosocomial pathogens associated with antimicrobial resistance. Other pathogens in the highest priority group included Helicobacter pylori, Respiratory Syncytial Virus, Varicella zoster virus and Hantavirus. DISCUSSION: While several pathogens from the highest priority group already have a high profile in national and international health policy documents, high scores for other pathogens (e.g., Helicobacter pylori, Respiratory syncytial virus or Hantavirus) indicate a possible under-recognised importance within the current German public health framework. A process to strengthen respective surveillance systems and research has been started. The prioritization methodology has worked well; its modular structure makes it potentially useful for other settings.",2011 Oct 4,"['Balabanova, Yanina', 'Gilsdorf, Andreas', 'Buda, Silke', 'Burger, Reinhard', 'Eckmanns, Tim', 'Gärtner, Barbara', 'Groß, Uwe', 'Haas, Walter', 'Hamouda, Osamah', 'Hübner, Johannes', 'Jänisch, Thomas', 'Kist, Manfred', 'Kramer, Michael H.', 'Ledig, Thomas', 'Mielke, Martin', 'Pulz, Matthias', 'Stark, Klaus', 'Suttorp, Norbert', 'Ulbrich, Uta', 'Wichmann, Ole', 'Krause, Gérard']",PLoS One,,,True
aa92ab17aef0b2ef391bad5a3590956c72794948,PMC,Estimating Infection Attack Rates and Severity in Real Time during an Influenza Pandemic: Analysis of Serial Cross-Sectional Serologic Surveillance Data,http://dx.doi.org/10.1371/journal.pmed.1001103,PMC3186812,21990967,CC BY,"BACKGROUND: In an emerging influenza pandemic, estimating severity (the probability of a severe outcome, such as hospitalization, if infected) is a public health priority. As many influenza infections are subclinical, sero-surveillance is needed to allow reliable real-time estimates of infection attack rate (IAR) and severity. METHODS AND FINDINGS: We tested 14,766 sera collected during the first wave of the 2009 pandemic in Hong Kong using viral microneutralization. We estimated IAR and infection-hospitalization probability (IHP) from the serial cross-sectional serologic data and hospitalization data. Had our serologic data been available weekly in real time, we would have obtained reliable IHP estimates 1 wk after, 1–2 wk before, and 3 wk after epidemic peak for individuals aged 5–14 y, 15–29 y, and 30–59 y. The ratio of IAR to pre-existing seroprevalence, which decreased with age, was a major determinant for the timeliness of reliable estimates. If we began sero-surveillance 3 wk after community transmission was confirmed, with 150, 350, and 500 specimens per week for individuals aged 5–14 y, 15–19 y, and 20–29 y, respectively, we would have obtained reliable IHP estimates for these age groups 4 wk before the peak. For 30–59 y olds, even 800 specimens per week would not have generated reliable estimates until the peak because the ratio of IAR to pre-existing seroprevalence for this age group was low. The performance of serial cross-sectional sero-surveillance substantially deteriorates if test specificity is not near 100% or pre-existing seroprevalence is not near zero. These potential limitations could be mitigated by choosing a higher titer cutoff for seropositivity. If the epidemic doubling time is longer than 6 d, then serial cross-sectional sero-surveillance with 300 specimens per week would yield reliable estimates when IAR reaches around 6%–10%. CONCLUSIONS: Serial cross-sectional serologic data together with clinical surveillance data can allow reliable real-time estimates of IAR and severity in an emerging pandemic. Sero-surveillance for pandemics should be considered. Please see later in the article for the Editors' Summary",2011 Oct 4,"['Wu, Joseph T.', 'Ho, Andrew', 'Ma, Edward S. K.', 'Lee, Cheuk Kwong', 'Chu, Daniel K. W.', 'Ho, Po-Lai', 'Hung, Ivan F. N.', 'Ho, Lai Ming', 'Lin, Che Kit', 'Tsang, Thomas', 'Lo, Su-Vui', 'Lau, Yu-Lung', 'Leung, Gabriel M.', 'Cowling, Benjamin J.', 'Peiris, J. S. Malik']",PLoS Med,,,True
ae0547531bec47c718e9f48ebb2454d9fdf4e487,PMC,Changes in Population Dynamics in Mutualistic versus Pathogenic Viruses,http://dx.doi.org/10.3390/v3010012,PMC3187592,21994724,CC BY,"Although generally regarded as pathogens, viruses can also be mutualists. A number of examples of extreme mutualism (i.e., symbiogenesis) have been well studied. Other examples of mutualism are less common, but this is likely because viruses have rarely been thought of as having any beneficial effects on their hosts. The effect of mutualism on the population dynamics of viruses is a topic that has not been addressed experimentally. However, the potential for understanding mutualism and how a virus might become a mutualist may be elucidated by understanding these dynamics.",2011 Jan 17,"Roossinck, Marilyn J.",Viruses,,,True
8a1da932b899d2a04b8e8ce1ccd2ce02bc352c9e,PMC,"A Potent, Broad-Spectrum Antiviral Agent that Targets Viral Membranes",http://dx.doi.org/10.3390/v2051106,PMC3187600,21994673,CC BY,"Commentary on Wolf, M.C.; Freiberg, A.N.; Zhang, T.; Akyol-Ataman, Z.; Grock, A.; Hong, P.W.; Li, J.; Watson, N.F.; Fang, A.Q.; Aguilar, H.C.; et al. A broad-spectrum antiviral targeting entry of enveloped viruses. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 3157–3162.",2010 May 4,"['Wojcechowskyj, Jason A.', 'Doms, Robert W.']",Viruses,,,True
b6fa578aa0397c1d6e2e0340b8581eb2c318974a,PMC,Role of Cellular Lipids in Positive-Sense RNA Virus Replication Complex Assembly and Function,http://dx.doi.org/10.3390/v2051055,PMC3187604,21994671,CC BY,"Positive-sense RNA viruses are responsible for frequent and often devastating diseases in humans, animals, and plants. However, the development of effective vaccines and anti-viral therapies targeted towards these pathogens has been hindered by an incomplete understanding of the molecular mechanisms involved in viral replication. One common feature of all positive-sense RNA viruses is the manipulation of host intracellular membranes for the assembly of functional viral RNA replication complexes. This review will discuss the interplay between cellular membranes and positive-sense RNA virus replication, and will focus specifically on the potential structural and functional roles for cellular lipids in this process.",2010 Apr 29,"['Stapleford, Kenneth A.', 'Miller, David J.']",Viruses,,,True
871ebc4ba030dbc666e9520d28b5f64e7a0ebf17,PMC,Unconventional Use of LC3 by Coronaviruses through the Alleged Subversion of the ERAD Tuning Pathway,http://dx.doi.org/10.3390/v3091610,PMC3187687,21994798,CC BY,"Pathogens of bacterial and viral origin hijack pathways operating in eukaryotic cells in many ways in order to gain access into the host, to establish themselves and to eventually produce their progeny. The detailed molecular characterization of the subversion mechanisms devised by pathogens to infect host cells is crucial to generate targets for therapeutic intervention. Here we review recent data indicating that coronaviruses probably co-opt membranous carriers derived from the endoplasmic reticulum, which contain proteins that regulate disposal of misfolded polypeptides, for their replication. In addition, we also present models describing potential mechanisms that coronaviruses could employ for this hijacking.",2011 Sep 5,"['Reggiori, Fulvio', 'de Haan, Cornelis A.M.', 'Molinari, Maurizio']",Viruses,,,True
5adc6c6cf5b6d7306ed52327e9ccec7a1512f1e4,PMC,Recombination in Avian Gamma-Coronavirus Infectious Bronchitis Virus,http://dx.doi.org/10.3390/v3091777,PMC3187689,21994806,CC BY,"Recombination in the family Coronaviridae has been well documented and is thought to be a contributing factor in the emergence and evolution of different coronaviral genotypes as well as different species of coronavirus. However, there are limited data available on the frequency and extent of recombination in coronaviruses in nature and particularly for the avian gamma-coronaviruses where only recently the emergence of a turkey coronavirus has been attributed solely to recombination. In this study, the full-length genomes of eight avian gamma-coronavirus infectious bronchitis virus (IBV) isolates were sequenced and along with other full-length IBV genomes available from GenBank were analyzed for recombination. Evidence of recombination was found in every sequence analyzed and was distributed throughout the entire genome. Areas that have the highest occurrence of recombination are located in regions of the genome that code for nonstructural proteins 2, 3 and 16, and the structural spike glycoprotein. The extent of the recombination observed, suggests that this may be one of the principal mechanisms for generating genetic and antigenic diversity within IBV. These data indicate that reticulate evolutionary change due to recombination in IBV, likely plays a major role in the origin and adaptation of the virus leading to new genetic types and strains of the virus.",2011 Sep 23,"['Thor, Sharmi W.', 'Hilt, Deborah A.', 'Kissinger, Jessica C.', 'Paterson, Andrew H.', 'Jackwood, Mark W.']",Viruses,,,True
c6d8bc1c51f8962ffbeb497c413e3e5e225b9c3e,PMC,Picornavirus Subversion of the Autophagy Pathway,http://dx.doi.org/10.3390/v3091549,PMC3187694,21994795,CC BY,"While autophagy has been shown to act as an anti-viral defense, the Picornaviridae avoid and, in many cases, subvert this pathway to promote their own replication. Evidence indicates that some picornaviruses hijack autophagy in order to induce autophagosome-like membrane structures for genomic RNA replication. Expression of picornavirus proteins can specifically induce the machinery of autophagy, although the mechanisms by which the viruses employ autophagy appear to differ. Many picornaviruses up-regulate autophagy in order to promote viral replication while some members of the family also inhibit degradation by autolysosomes. Here we explore the unusual relationship of this medically important family of viruses with a degradative mechanism of innate immunity.",2011 Aug 26,"['Klein, Kathryn A.', 'Jackson, William T.']",Viruses,,,True
a6f36e3233319626ec737895c1d52dedd7aac0bf,PMC,Recombination in Eukaryotic Single Stranded DNA Viruses,http://dx.doi.org/10.3390/v3091699,PMC3187698,21994803,CC BY,"Although single stranded (ss) DNA viruses that infect humans and their domesticated animals do not generally cause major diseases, the arthropod borne ssDNA viruses of plants do, and as a result seriously constrain food production in most temperate regions of the world. Besides the well known plant and animal-infecting ssDNA viruses, it has recently become apparent through metagenomic surveys of ssDNA molecules that there also exist large numbers of other diverse ssDNA viruses within almost all terrestrial and aquatic environments. The host ranges of these viruses probably span the tree of life and they are likely to be important components of global ecosystems. Various lines of evidence suggest that a pivotal evolutionary process during the generation of this global ssDNA virus diversity has probably been genetic recombination. High rates of homologous recombination, non-homologous recombination and genome component reassortment are known to occur within and between various different ssDNA virus species and we look here at the various roles that these different types of recombination may play, both in the day-to-day biology, and in the longer term evolution, of these viruses. We specifically focus on the ecological, biochemical and selective factors underlying patterns of genetic exchange detectable amongst the ssDNA viruses and discuss how these should all be considered when assessing the adaptive value of recombination during ssDNA virus evolution.",2011 Sep 13,"['Martin, Darren P.', 'Biagini, Philippe', 'Lefeuvre, Pierre', 'Golden, Michael', 'Roumagnac, Philippe', 'Varsani, Arvind']",Viruses,,,True
32b29df5230354c35d8734b996e5e45501a5111b,PMC,A Vesicular Stomatitis Virus Replicon-Based Bioassay for the Rapid and Sensitive Determination of Multi-Species Type I Interferon,http://dx.doi.org/10.1371/journal.pone.0025858,PMC3187809,21998709,CC BY,"Type I interferons (IFN) comprise a family of cytokines that signal through a common cellular receptor to induce a plethora of genes with antiviral and other activities. Recombinant IFNs are used for the treatment of hepatitis C virus infection, multiple sclerosis, and certain malignancies. The capability of type I IFN to suppress virus replication and resultant cytopathic effects is frequently used to measure their bioactivity. However, these assays are time-consuming and require appropriate biosafety containment. In this study, an improved IFN assay is presented which is based on a recombinant vesicular stomatitis virus (VSV) replicon encoding two reporter proteins, firefly luciferase and green fluorescent protein. The vector lacks the essential envelope glycoprotein (G) gene of VSV and is propagated on a G protein-expressing transgenic cell line. Several mammalian and avian cells turned out to be susceptible to infection with the complemented replicon particles. Infected cells readily expressed the reporter proteins at high levels five hours post infection. When human fibroblasts were treated with serial dilutions of human IFN-β prior to infection, reporter expression was accordingly suppressed. This method was more sensitive and faster than a classical IFN bioassay based on VSV cytopathic effects. In addition, the antiviral activity of human IFN-λ (interleukin-29), a type III IFN, was determined on Calu-3 cells. Both IFN-β and IFN-λ were acid-stable, but only IFN-β was resistant to alkaline treatment. The antiviral activities of canine, porcine, and avian type I IFN were analysed with cell lines derived from the corresponding species. This safe bioassay will be useful for the rapid and sensitive quantification of multi-species type I IFN and potentially other antiviral cytokines.",2011 Oct 5,"['Berger Rentsch, Marianne', 'Zimmer, Gert']",PLoS One,,,True
fc5a448b2c227817cd29625972acb40e853cac89,PMC,Conceptualising the technical relationship of animal disease surveillance to intervention and mitigation as a basis for economic analysis,http://dx.doi.org/10.1186/1472-6963-11-225,PMC3189394,21929812,CC BY,"BACKGROUND: Surveillance and intervention are resource-using activities of strategies to mitigate the unwanted effects of disease. Resources are scarce, and allocating them to disease mitigation instead of other uses necessarily involves the loss of alternative sources of benefit to people. For society to obtain the maximum benefits from using resources, the gains from disease mitigation must be compared to the resource costs, guiding decisions made with the objective of achieving the optimal net outcome. DISCUSSION: Economics provides criteria to guide decisions aimed at optimising the net benefits from the use of scarce resources. Assessing the benefits of disease mitigation is no exception. However, the technical complexity of mitigation means that economic evaluation is not straightforward because of the technical relationship of surveillance to intervention. We argue that analysis of the magnitudes and distribution of benefits and costs for any given strategy, and hence the outcome in net terms, requires that mitigation is considered in three conceptually distinct stages. In Stage I, 'sustainment', the mitigation objective is to sustain a free or acceptable status by preventing an increase of a pathogen or eliminating it when it occurs. The role of surveillance is to document that the pathogen remains below a defined threshold, giving early warning of an increase in incidence or other significant changes in risk, and enabling early response. If a pathogen is not contained, the situation needs to be assessed as Stage II, 'investigation'. Here, surveillance obtains critical epidemiological information to decide on the appropriate intervention strategy to reduce or eradicate a disease in Stage III, 'implementation'. Stage III surveillance informs the choice, timing, and scale of interventions and documents the progress of interventions directed at prevalence reduction in the population. SUMMARY: This article originates from a research project to develop a conceptual framework and practical tool for the economic evaluation of surveillance. Exploring the technical relationship between mitigation as a source of economic value and surveillance and intervention as sources of economic cost is crucial. A framework linking the key technical relationships is proposed. Three conceptually distinct stages of mitigation are identified. Avian influenza, salmonella, and foot and mouth disease are presented to illustrate the framework.",2011 Sep 19,"['Häsler, Barbara', 'Howe, Keith S', 'Stärk, Katharina DC']",BMC Health Serv Res,,,True
b85bcfe513307afbac6c3bd5866dc0c0aecd28a5,PMC,"Characterization of Neutralizing Profiles in HIV-1 Infected Patients from whom the HJ16, HGN194 and HK20 mAbs were Obtained",http://dx.doi.org/10.1371/journal.pone.0025488,PMC3189917,22016769,CC BY,"Several new human monoclonal antibodies (mAbs) with a neutralizing potential across different subtypes have recently been described. Three mAbs, HJ16, HGN194 and HK20, were obtained from patients within the HIV-1 cohort of the Institute of Tropical Medicine (ITM). Our aim was to generate immunization antibodies equivalent to those seen in plasma. Here, we describe the selection and characterization of patient plasma and their mAbs, using a range of neutralization assays, including several peripheral blood mononuclear cell (PBMC) based assays and replicating primary viruses as well as cell line based assays and pseudoviruses (PV). The principal criterion for selection of patient plasma was the activity in an ‘extended incubation phase’ PBMC assay. Neutralizing Abs, derived from their memory B cells, were then selected by ELISA with envelope proteins as solid phase. MAbs were subsequently tested in a high-throughput HOS-PV assay to assess functional neutralization. The present study indicates that the strong profiles in the patients' plasma were not solely due to antibodies represented by the newly isolated mAbs. Although results from the various assays were divergent, they by and large indicate that neutralizing Abs to other epitopes of the HIV-1 envelope are present in the plasma and synergy between Abs may be important. Thus, the spectrum of the obtained mAbs does not cover the range of cross-reactivity seen in plasma in these carefully selected patients irrespective of which neutralization assay is used. Nevertheless, these mAbs are relevant for immunogen discovery because they bind to the recombinant glycoproteins to which the immune response needs to be targeted in vivo. Our observations illustrate the remaining challenges required for successful immunogen design and development.",2011 Oct 10,"['Balla-Jhagjhoorsingh, Sunita S.', 'Willems, Betty', 'Heyndrickx, Liesbeth', 'Heyndrickx, Leo', 'Vereecken, Katleen', 'Janssens, Wouter', 'Seaman, Michael S.', 'Corti, Davide', 'Lanzavecchia, Antonio', 'Davis, David', 'Vanham, Guido']",PLoS One,,,True
ca866226d436ba4c39fe854f9cc568f08638868d,PMC,EBV-gp350 Confers B-Cell Tropism to Tailored Exosomes and Is a Neo-Antigen in Normal and Malignant B Cells—A New Option for the Treatment of B-CLL,http://dx.doi.org/10.1371/journal.pone.0025294,PMC3189918,22022385,CC BY,"gp350, the major envelope protein of Epstein-Barr-Virus, confers B-cell tropism to the virus by interacting with the B lineage marker CD21. Here we utilize gp350 to generate tailored exosomes with an identical tropism. These exosomes can be used for the targeted co-transfer of functional proteins to normal and malignant human B cells. We demonstrate here the co-transfer of functional CD154 protein on tailored gp350+ exosomes to malignant B blasts from patients with B chronic lymphocytic leukemia (B-CLL), rendering B blasts immunogenic to tumor-reactive autologous T cells. Intriguingly, engulfment of gp350+ exosomes by B-CLL cells and presentation of gp350-derived peptides also re-stimulated EBV-specific T cells and redirected the strong antiviral cellular immune response in patients to leukemic B cells. In essence, we show that gp350 alone confers B-cell tropism to exosomes and that these exosomes can be further engineered to simultaneously trigger virus- and tumor-specific immune responses. The simultaneous exploitation of gp350 as a tropism molecule for tailored exosomes and as a neo-antigen in malignant B cells provides a novel attractive strategy for immunotherapy of B-CLL and other B-cell malignancies.",2011 Oct 10,"['Ruiss, Romana', 'Jochum, Simon', 'Mocikat, Ralph', 'Hammerschmidt, Wolfgang', 'Zeidler, Reinhard']",PLoS One,,,True
f659c70f5c28f2b2694bc76b0a57b47d8d6362d5,PMC,Viral Double-Strand RNA-Binding Proteins Can Enhance Innate Immune Signaling by Toll-Like Receptor 3,http://dx.doi.org/10.1371/journal.pone.0025837,PMC3189932,22016778,CC BY,"Toll-like Receptor 3 (TLR3) detects double-stranded (ds) RNAs to activate innate immune responses. While poly(I:C) is an excellent agonist for TLR3 in several cell lines and in human peripheral blood mononuclear cells, viral dsRNAs tend to be poor agonists, leading to the hypothesis that additional factor(s) are likely required to allow TLR3 to respond to viral dsRNAs. TLR3 signaling was examined in a lung epithelial cell line by quantifying cytokine production and in human embryonic kidney cells by quantifying luciferase reporter levels. Recombinant 1b hepatitis C virus polymerase was found to enhance TLR3 signaling in the lung epithelial BEAS-2B cells when added to the media along with either poly(I:C) or viral dsRNAs. The polymerase from the genotype 2a JFH-1 HCV was a poor enhancer of TLR3 signaling until it was mutated to favor a conformation that could bind better to a partially duplexed RNA. The 1b polymerase also co-localizes with TLR3 in endosomes. RNA-binding capsid proteins (CPs) from two positive-strand RNA viruses and the hepadenavirus hepatitis B virus (HBV) were also potent enhancers of TLR3 signaling by poly(I:C) or viral dsRNAs. A truncated version of the HBV CP that lacked an arginine-rich RNA-binding domain was unable to enhance TLR3 signaling. These results demonstrate that several viral RNA-binding proteins can enhance the dsRNA-dependent innate immune response initiated by TLR3.",2011 Oct 10,"['Lai, Yvonne', 'Yi, Guanghui', 'Chen, Alice', 'Bhardwaj, Kanchan', 'Tragesser, Brady J.', 'Rodrigo A. Valverde,', 'Zlotnick, Adam', 'Mukhopadhyay, Suchetana', 'Ranjith-Kumar, C. T.', 'Kao, C. Cheng']",PLoS One,,,True
5f36e6c3da64e8d95c81d9c63ad4909144f9191c,PMC,Specific Viruses Detected in Nigerian Children in Association with Acute Respiratory Disease,http://dx.doi.org/10.1155/2011/690286,PMC3191740,22007241,CC BY,"Occurrence of different viruses in acute respiratory tract infections of Nigerian children was examined. Respiratory swabs were collected from 246 children referred to hospital clinics because of acute respiratory symptoms from February through May 2009. Validated real-time RT-PCR techniques revealed nucleic acids of at least one virus group in 189 specimens (77%). Human rhinoviruses and parainfluenza viruses were present each in one third of the children. Adenoviruses, enteroviruses, human metapneumovirus, human bocavirus, and influenza C virus were also relatively common. Possibly due to their seasonal occurrence, influenza A and B virus, and respiratory syncytial virus were detected rarely. We conclude that all major groups of respiratory tract viruses are causing illness in Nigerian children.",2011 Oct 11,"['Akinloye, Oluwabukola M.', 'Rönkkö, Esa', 'Savolainen-Kopra, Carita', 'Ziegler, Thedi', 'Iwalokun, Bamidele A.', 'Deji-Agboola, Mope A.', 'Oluwadun, Afolabi', 'Roivainen, Merja', 'Adu, Festus D.', 'Hovi, Tapani']",J Trop Med,,,True
15f2b1915443fff0466f0dd89c7c0ab6761833b4,PMC,Detection of a Fourth Orbivirus Non-Structural Protein,http://dx.doi.org/10.1371/journal.pone.0025697,PMC3192121,22022432,CC BY,"The genus Orbivirus includes both insect and tick-borne viruses. The orbivirus genome, composed of 10 segments of dsRNA, encodes 7 structural proteins (VP1–VP7) and 3 non-structural proteins (NS1–NS3). An open reading frame (ORF) that spans almost the entire length of genome segment-9 (Seg-9) encodes VP6 (the viral helicase). However, bioinformatic analysis recently identified an overlapping ORF (ORFX) in Seg-9. We show that ORFX encodes a new non-structural protein, identified here as NS4. Western blotting and confocal fluorescence microscopy, using antibodies raised against recombinant NS4 from Bluetongue virus (BTV, which is insect-borne), or Great Island virus (GIV, which is tick-borne), demonstrate that these proteins are synthesised in BTV or GIV infected mammalian cells, respectively. BTV NS4 is also expressed in Culicoides insect cells. NS4 forms aggregates throughout the cytoplasm as well as in the nucleus, consistent with identification of nuclear localisation signals within the NS4 sequence. Bioinformatic analyses indicate that NS4 contains coiled-coils, is related to proteins that bind nucleic acids, or are associated with membranes and shows similarities to nucleolar protein UTP20 (a processome subunit). Recombinant NS4 of GIV protects dsRNA from degradation by endoribonucleases of the RNAse III family, indicating that it interacts with dsRNA. However, BTV NS4, which is only half the putative size of the GIV NS4, did not protect dsRNA from RNAse III cleavage. NS4 of both GIV and BTV protect DNA from degradation by DNAse. NS4 was found to associate with lipid droplets in cells infected with BTV or GIV or transfected with a plasmid expressing NS4.",2011 Oct 12,"['Belhouchet, Mourad', 'Mohd Jaafar, Fauziah', 'Firth, Andrew E.', 'Grimes, Jonathan M.', 'Mertens, Peter P. C.', 'Attoui, Houssam']",PLoS One,,,True
3ec7aa1d4381bbaa7f5fa69fa8eb7cc1d90a39f1,PMC,Geographic Distribution and Risk Factors of the Initial Adult Hospitalized Cases of 2009 Pandemic Influenza A (H1N1) Virus Infection in Mainland China,http://dx.doi.org/10.1371/journal.pone.0025934,PMC3192122,22022474,CC BY,"BACKGROUND: As of 31(st) March 2010, more than 127,000 confirmed cases of 2009 pandemic influenza A (H1N1), including 800 deaths, were reported in mainland China. The distribution and characteristics of the confirmed cases in the initial phase of this pandemic in this country are largely unknown. The present study aimed to characterize the geographic distribution and patient characteristics of H1N1 infection in the 2009 pandemic as well as to identify potential risk factors associated with adverse patient outcome in China, through retrospective analyses of 885 hospitalized cases with confirmed H1N1 infection. METHODOLOGY/PRINCIPAL FINDINGS: The proportional hazards model was employed to detect risk factors for adverse outcome; the geo-statistical maps were used to characterize the distribution of all 2668 confirmed H1N1 patients throughout mainland China. The number of new cases increased slowly in May, 2009, but rapidly between June and August of the year. Confirmed cases were reported in 26 provinces; Beijing, Guangdong, Shanghai, Zhejiang and Fujian were the top five regions of the incidence of the virus infection. After being adjusted for gender, age, chronic pulmonary disease and other general symptoms, delay for more than two days before hospital admission (HR: 0.6; 95%CI: 0.5–0.7) and delayed onset of the H1N1-specific respiratory symptoms (HR: 0.3; 95%CI: 0.2–0.4) were associated with adverse patient outcome. CONCLUSIONS/SIGNIFICANCE: The 2009 pandemic influenza A affected east and southeast coastal provinces and most populous cities more severely than other regions in mainland China due to higher risk of high level traffic-, high population density-, and high population mobility-associated H1N1 transmission.The clinical symptoms were mild in the initial phase of infection. Delayed hospital admission and delayed appearance of respiratory symptoms were among the major risk factors for poor patient outcome. These findings may have significant implications in the future pandemic preparedness and response.",2011 Oct 12,"['Liu, Yunning', 'Wang, Wei', 'Li, Xia', 'Wang, Hong', 'Luo, Yanxia', 'Wu, Lijuan', 'Guo, Xiuhua']",PLoS One,,,True
121f06c44cde088607a6f4d16098eb6101513c01,PMC,Pulsed electromagnetic fields stimulation prevents steroid-induced osteonecrosis in rats,http://dx.doi.org/10.1186/1471-2474-12-215,PMC3192716,21958301,CC BY,"BACKGROUND: Pulsed electromagnetic fields (PEMF) stimulation has been used successfully to treat nonunion fractures and femoral head osteonecrosis, but relatively little is known about its effects on preventing steroid-induced osteonecrosis. The purpose of the study was to investigate the effects of PEMF stimulation on the prevention of steroid-induced osteonecrosis in rats and explore the underlying mechanisms. METHODS: Seventy-two male adult Wistar rats were divided into three groups and treated as follows. (1) PEMF stimulation group (PEMF group, n = 24): intravenously injected with lipopolysaccharide (LPS, 10 μg/kg) on day 0 and intramuscularly injected with methylprednisolone acetate (MPSL, 20 mg/kg) on days 1, 2 and 3, then subjected to PEMF stimulation 4 h per day for 1 to 8 weeks. (2) Methylprednisolone-treated group (MPSL group, n = 24): injected the same dose of LPS and MPSL as the PEMF group but without exposure to PEMF. (3) Control group (PS group, n = 24): injected 0.9% saline in the same mode at the same time points. The incidence of osteonecrosis, serum lipid levels and the mRNA and protein expression of transforming growth factor β1 (TGF-β1) in the proximal femur were measured 1, 2, 4 and 8 weeks after the last MPSL (or saline) injection. RESULTS: The incidence of osteonecrosis in the PEMF group (29%) was significantly lower than that observed in the MPSL group (75%), while no osteonecrosis was observed in the PS group. The serum lipid levels were significantly lower in the PEMF and PS groups than in the MPSL group. Compared with the MPSL and PS groups, the mRNA expression of TGF-β1 increased, reaching a peak 1 week after PEMF treatment, and remained high for 4 weeks, then declined at 8 weeks, whereas the protein expression of TGF-β1 increased, reaching a peak at 2 weeks after PEMF treatment, and remained high for 8 weeks. CONCLUSIONS: PEMF stimulation can prevent steroid-induced osteonecrosis in rats, and the underlying mechanisms involve decreased serum lipid levels and increased expression of TGF-β1.",2011 Sep 29,"['Ding, Shuai', 'Peng, Hao', 'Fang, Hong-Song', 'Zhou, Jian-Lin', 'Wang, Zhe']",BMC Musculoskelet Disord,,,True
eafa4d1bd1e62bf88d6d2813002cfe6c33be8b95,PMC,Investigation of a Potential Zoonotic Transmission of Orthoreovirus Associated with Acute Influenza-Like Illness in an Adult Patient,http://dx.doi.org/10.1371/journal.pone.0025434,PMC3192755,22022394,CC BY,"Bats are increasingly being recognized as important reservoir hosts for a large number of viruses, some of them can be highly virulent when they infect human and livestock animals. Among the new bat zoonotic viruses discovered in recent years, several reoviruses (respiratory enteric orphan viruses) were found to be able to cause acute respiratory infections in humans, which included Melaka and Kampar viruses discovered in Malaysia, all of them belong to the genus Orthoreovirus, family Reoviridae. In this report, we describe the isolation of a highly related virus from an adult patient who suffered acute respiratory illness in Malaysia. Although there was no direct evidence of bat origin, epidemiological study indicated the potential exposure of the patient to bats before the onset of disease. The current study further demonstrates that spillover events of different strains of related orthoreoviruses from bats to humans are occurring on a regular basis, which calls for more intensive and systematic surveillances to fully assess the true public health impact of these newly discovered bat-borne zoonotic reoviruses.",2011 Oct 13,"['Chua, Kaw Bing', 'Voon, Kenny', 'Yu, Meng', 'Keniscope, Canady', 'Abdul Rasid, Kasri', 'Wang, Lin-Fa']",PLoS One,,,True
4296edbb527d1e55ad2079c76f619659e0b5720d,PMC,Therapy and Long-Term Prophylaxis of Vaccinia Virus Respiratory Infections in Mice with an Adenovirus-Vectored Interferon Alpha (mDEF201),http://dx.doi.org/10.1371/journal.pone.0026330,PMC3192798,22022603,CC BY,"An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201) was evaluated for efficacy against lethal vaccinia virus (WR strain) respiratory infections in mice. mDEF201 was administered as a single intranasal treatment either prophylactically or therapeutically at doses of 10(6) to 10(8) plaque forming units/mouse. When the prophylactic treatment was given at 56 days prior to infection, it protected 90% of animals from death (100% protection for treatments given between 1–49 days pre-infection), with minimal weight loss occurring during infection. Surviving animals re-challenged with virus 22 days after the primary infection were protected from death, indicating that mDEF201 did not compromise the immune response against the initial infection. Post-exposure therapy was given between 6–24 h after vaccinia virus exposure and protection was afforded by a 10(8) dose of mDEF201 given at 24 h, whereas a 10(7) dose was effective up to 12 h. Comparisons were made of the ability of mDEF201, given either 28 or 1 day prior to infection, to inhibit tissue virus titers and lung infection parameters. Lung, liver, and spleen virus titers were inhibited to nearly the same extent by either treatment, as were lung weights and lung hemorrhage scores (indicators of pneumonitis). Lung virus titers were significantly (>100-fold) lower than in the placebo group, and the other infection parameters in mDEF201 treated mice were nearly at baseline. In contrast, viral titers and lung infection parameters were high in the placebo group on day 5 of the infection. These results demonstrate the long-acting prophylactic and treatment capacity of mDEF201 to combat vaccinia virus infections.",2011 Oct 13,"['Smee, Donald F.', 'Wong, Min-Hui', 'Russell, Andrew', 'Ennis, Jane', 'Turner, Jeffrey D.']",PLoS One,,,True
4ec19e6a2799bf2bebe635732de198d04ddedf64,PMC,Biochemical and Structural Insights into the Mechanisms of SARS Coronavirus RNA Ribose 2′-O-Methylation by nsp16/nsp10 Protein Complex,http://dx.doi.org/10.1371/journal.ppat.1002294,PMC3192843,22022266,CC BY,"The 5′-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5′-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2′-O positions, catalyzed by nsp14 N7-MTase and nsp16 2′-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2′-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs.",2011 Oct 13,"['Chen, Yu', 'Su, Ceyang', 'Ke, Min', 'Jin, Xu', 'Xu, Lirong', 'Zhang, Zhou', 'Wu, Andong', 'Sun, Ying', 'Yang, Zhouning', 'Tien, Po', 'Ahola, Tero', 'Liang, Yi', 'Liu, Xinqi', 'Guo, Deyin']",PLoS Pathog,,,True
2c0c7b9bdc81461fbf533ae6b89fd78326651306,PMC,Improved vaccine protection against retrovirus infection after co-administration of adenoviral vectors encoding viral antigens and type I interferon subtypes,http://dx.doi.org/10.1186/1742-4690-8-75,PMC3193818,21943056,CC BY,"BACKGROUND: Type I interferons (IFNs) exhibit direct antiviral effects, but also distinct immunomodulatory properties. In this study, we analyzed type I IFN subtypes for their effect on prophylactic adenovirus-based anti-retroviral vaccination of mice against Friend retrovirus (FV) or HIV. RESULTS: Mice were vaccinated with adenoviral vectors encoding FV Env and Gag proteins alone or in combination with vectors encoding IFNα1, IFNα2, IFNα4, IFNα5, IFNα6, IFNα9 or IFNβ. Only the co-administration of adenoviral vectors encoding IFNα2, IFNα4, IFNα6 and IFNα9 resulted in strongly improved immune protection of vaccinated mice from subsequent FV challenge infection with high control over FV-induced splenomegaly and reduced viral loads. The level of protection correlated with augmented virus-specific CD4(+ )T cell responses and enhanced antibody titers. Similar results were obtained when mice were vaccinated against HIV with adenoviral vectors encoding HIV Env and Gag-Pol in combination with various type I IFN encoding vectors. Here mainly CD4(+ )T cell responses were enhanced by IFNα subtypes. CONCLUSIONS: Our results indicate that certain IFNα subtypes have the potential to improve the protective effect of adenovirus-based vaccines against retroviruses. This correlated with augmented virus-specific CD4(+ )T cell and antibody responses. Thus, co-expression of select type I IFNs may be a valuable tool for the development of anti-retroviral vaccines.",2011 Sep 26,"['Bayer, Wibke', 'Lietz, Ruth', 'Ontikatze, Teona', 'Johrden, Lena', 'Tenbusch, Matthias', 'Nabi, Ghulam', 'Schimmer, Simone', 'Groitl, Peter', 'Wolf, Hans', 'Berry, Cassandra M', 'Überla, Klaus', 'Dittmer, Ulf', 'Wildner, Oliver']",Retrovirology,,,True
e3d75d7baf118918395a6950b724215ec2c8023c,PMC,Identification and Typing of Human Enterovirus: A Genomic Barcode Approach,http://dx.doi.org/10.1371/journal.pone.0026296,PMC3194813,22022592,CC BY,"Identification and typing of human enterovirus (HEVs) are important to pathogen detection and therapy. Previous phylogeny-based typing methods are mainly based on multiple sequence alignments of specific genes in the HEVs, but the results are not stable with respect to different choices of genes. Here we report a novel method for identification and typing of HEVs based on information derived from their whole genomes. Specifically, we calculate the k-mer based barcode image for each genome, HEV or other human viruses, for a fixed k, 199% identity). These results show that the novel bunyavirus (HNF virus) is strongly correlated with FTLS.",2011 Nov 17,"['Xu, Bianli', 'Liu, Licheng', 'Huang, Xueyong', 'Ma, Hong', 'Zhang, Yuan', 'Du, Yanhua', 'Wang, Pengzhi', 'Tang, Xiaoyan', 'Wang, Haifeng', 'Kang, Kai', 'Zhang, Shiqiang', 'Zhao, Guohua', 'Wu, Weili', 'Yang, Yinhui', 'Chen, Haomin', 'Mu, Feng', 'Chen, Weijun']",PLoS Pathog,,,True
5016b361dce58077b3d647b0772425e079f98d8d,PMC,Neurons are MHC Class I-Dependent Targets for CD8 T Cells upon Neurotropic Viral Infection,http://dx.doi.org/10.1371/journal.ppat.1002393,PMC3219726,22114563,CC BY,"Following infection of the central nervous system (CNS), the immune system is faced with the challenge of eliminating the pathogen without causing significant damage to neurons, which have limited capacities of renewal. In particular, it was thought that neurons were protected from direct attack by cytotoxic T lymphocytes (CTL) because they do not express major histocompatibility class I (MHC I) molecules, at least at steady state. To date, most of our current knowledge on the specifics of neuron-CTL interaction is based on studies artificially inducing MHC I expression on neurons, loading them with exogenous peptide and applying CTL clones or lines often differentiated in culture. Thus, much remains to be uncovered regarding the modalities of the interaction between infected neurons and antiviral CD8 T cells in the course of a natural disease. Here, we used the model of neuroinflammation caused by neurotropic Borna disease virus (BDV), in which virus-specific CTL have been demonstrated as the main immune effectors triggering disease. We tested the pathogenic properties of brain-isolated CD8 T cells against pure neuronal cultures infected with BDV. We observed that BDV infection of cortical neurons triggered a significant up regulation of MHC I molecules, rendering them susceptible to recognition by antiviral CTL, freshly isolated from the brains of acutely infected rats. Using real-time imaging, we analyzed the spatio-temporal relationships between neurons and CTL. Brain-isolated CTL exhibited a reduced mobility and established stable contacts with BDV-infected neurons, in an antigen- and MHC-dependent manner. This interaction induced rapid morphological changes of the neurons, without immediate killing or impairment of electrical activity. Early signs of neuronal apoptosis were detected only hours after this initial contact. Thus, our results show that infected neurons can be recognized efficiently by brain-isolated antiviral CD8 T cells and uncover the unusual modalities of CTL-induced neuronal damage.",2011 Nov 17,"['Chevalier, Grégoire', 'Suberbielle, Elsa', 'Monnet, Céline', 'Duplan, Valérie', 'Martin-Blondel, Guillaume', 'Farrugia, Fanny', 'Le Masson, Gwendal', 'Liblau, Roland', 'Gonzalez-Dunia, Daniel']",PLoS Pathog,,,True
8abf33baca8c7abbbf6ca5f56b404b79f658dd26,PMC,Calf health from birth to weaning. III. housing and management of calf pneumonia,http://dx.doi.org/10.1186/2046-0481-64-14,PMC3220626,22018053,CC BY,"Calfhood diseases have a major impact on the economic viability of cattle operations. A three part review series has been developed focusing on calf health from birth to weaning. In this paper, the last of the three part series, we review disease prevention and management with particular reference to pneumonia, focusing primarily on the pre-weaned calf. Pneumonia in recently weaned suckler calves is also considered, where the key risk factors are related to the time of weaning. Weaning of the suckler calf is often combined with additional stressors including a change in nutrition, environmental change, transport and painful husbandry procedures (castration, dehorning). The reduction of the cumulative effects of these multiple stressors around the time of weaning together with vaccination programmes (preconditioning) can reduce subsequent morbidity and mortality in the feedlot. In most studies, calves housed individually and calves housed outdoors with shelter, are associated with decreased risk of disease. Even though it poses greater management challenges, successful group housing of calves is possible. Special emphasis should be given to equal age groups and to keeping groups stable once they are formed. The management of pneumonia in calves is reliant on a sound understanding of aetiology, relevant risk factors, and of effective approaches to diagnosis and treatment. Early signs of pneumonia include increased respiratory rate and fever, followed by depression. The single most important factor determining the success of therapy in calves with pneumonia is early onset of treatment, and subsequent adequate duration of treatment. The efficacy and economical viability of vaccination against respiratory disease in calves remains unclear.",2011 Oct 21,"['Lorenz, Ingrid', 'Earley, Bernadette', 'Gilmore, John', 'Hogan, Ian', 'Kennedy, Emer', 'More, Simon J']",Ir Vet J,,,True
c56d753d8b3c0fb68cb1bd22f0b7d10eb3c08e93,PMC,Survival of Influenza A(H1N1) on Materials Found in Households: Implications for Infection Control,http://dx.doi.org/10.1371/journal.pone.0027932,PMC3222642,22132172,CC BY,"BACKGROUND: The majority of influenza transmission occurs in homes, schools and workplaces, where many frequently touched communal items are situated. However the importance of transmission via fomites is unclear since few data exist on the survival of virus on commonly touched surfaces. We therefore measured the viability over time of two H1N1 influenza strains applied to a variety of materials commonly found in households and workplaces. METHODOLOGY AND PRINCIPAL FINDINGS: Influenza A/PuertoRico/8/34 (PR8) or A/Cambridge/AHO4/2009 (pandemic H1N1) viruses were inoculated onto a wide range of surfaces used in home and work environments, then sampled at set times following incubation at stabilised temperature and humidity. Virus genome was measured by RT-PCR; plaque assay (for PR8) or fluorescent focus formation (for pandemic H1N1) was used to assess the survival of viable virus. CONCLUSIONS/SIGNIFICANCE: The genome of either virus could be detected on most surfaces 24 h after application with relatively little drop in copy number, with the exception of unsealed wood surfaces. In contrast, virus viability dropped much more rapidly. Live virus was recovered from most surfaces tested four hours after application and from some non-porous materials after nine hours, but had fallen below the level of detection from all surfaces at 24 h. We conclude that influenza A transmission via fomites is possible but unlikely to occur for long periods after surface contamination (unless re-inoculation occurs). In situations involving a high probability of influenza transmission, our data suggest a hierarchy of priorities for surface decontamination in the multi-surface environments of home and hospitals.",2011 Nov 22,"['Greatorex, Jane S.', 'Digard, Paul', 'Curran, Martin D.', 'Moynihan, Robert', 'Wensley, Harrison', 'Wreghitt, Tim', 'Varsani, Harsha', 'Garcia, Fayna', 'Enstone, Joanne', 'Nguyen-Van-Tam, Jonathan S.']",PLoS One,,,True
6bcf5a5f877be9a08113db6aec4a409f8d111895,PMC,Respiratory failure presenting in H1N1 influenza with Legionnaires disease: two case reports,http://dx.doi.org/10.1186/1752-1947-5-520,PMC3223529,22018019,CC BY,"INTRODUCTION: Media sensationalism on the H1N1 outbreak may have influenced decisional processes and clinical diagnosis. CASE PRESENTATION: We report two cases of patients who presented in 2009 with coexisting H1N1 virus and Legionella infections: a 69-year-old Caucasian man and a 71-year-old Caucasian woman. In our cases all the signs and symptoms, including vomiting, progressive respiratory disease leading to respiratory failure, refractory hypoxemia, leukopenia, lymphopenia, thrombocytopenia, and elevated levels of creatine kinase and hepatic aminotransferases, were consistent with critical illness due to 2009 H1N1 virus infection. Other infectious disorders may mimic H1N1 viral infection especially Legionnaires' disease. Because the swine flu H1N1 pandemic occurred in Autumn in Italy, Legionnaires disease was to be highly suspected since the peak incidence usually occurs in early fall. We do think that our immediate suspicion of Legionella infection based on clinical history and X-ray abnormalities was fundamental for a successful resolution. CONCLUSION: Our two case reports suggest that patients with H1N1 should be screened for Legionella, which is not currently common practice. This is particularly important since the signs and symptoms of both infections are similar.",2011 Oct 21,"['Iannuzzi, Michele', 'De Robertis, Edoardo', 'Piazza, Ornella', 'Rispoli, Fabio', 'Servillo, Giuseppe', 'Tufano, Rosalba']",J Med Case Reports,,,True
8871ee344c8ca239b4aa5077f5e438075663299b,PMC,"Field Epidemiology and Laboratory Training Programs in sub-Saharan Africa from 2004 to 2010: need, the process, and prospects",,PMC3224071,22187606,CC BY,"As of 2010 sub-Saharan Africa had approximately 865 million inhabitants living with numerous public health challenges. Several public health initiatives [e.g., the United States (US) President's Emergency Plan for AIDS Relief and the US President's Malaria Initiative] have been very successful at reducing mortality from priority diseases. A competently trained public health workforce that can operate multi-disease surveillance and response systems is necessary to build upon and sustain these successes and to address other public health problems. Sub-Saharan Africa appears to have weathered the recent global economic downturn remarkably well and its increasing middle class may soon demand stronger public health systems to protect communities. The Epidemic Intelligence Service (EIS) program of the US Centers for Disease Control and Prevention (CDC) has been the backbone of public health surveillance and response in the US during its 60 years of existence. EIS has been adapted internationally to create the Field Epidemiology Training Program (FETP) in several countries. In the 1990s CDC and the Rockefeller Foundation collaborated with the Uganda and Zimbabwe ministries of health and local universities to create 2-year Public Health Schools Without Walls (PHSWOWs) which were based on the FETP model. In 2004 the FETP model was further adapted to create the Field Epidemiology and Laboratory Training Program (FELTP) in Kenya to conduct joint competency-based training for field epidemiologists and public health laboratory scientists providing a master's degree to participants upon completion. The FELTP model has been implemented in several additional countries in sub-Saharan Africa. By the end of 2010 these 10 FELTPs and two PHSWOWs covered 613 million of the 865 million people in sub-Saharan Africa and had enrolled 743 public health professionals. We describe the process that we used to develop 10 FELTPs covering 15 countries in sub-Saharan Africa from 2004 to 2010 as a strategy to develop a locally trained public health workforce that can operate multi-disease surveillance and response systems.",2011 Oct 19,"['Nsubuga, Peter', 'Johnson, Kenneth', 'Tetteh, Christopher', 'Oundo, Joseph', 'Weathers, Andrew', 'Vaughan, James', 'Elbon, Suzanne', 'Tshimanga, Mufuta', 'Ndugulile, Faustine', 'Ohuabunwo, Chima', 'Evering-Watley, Michele', 'Mosha, Fausta', 'Oleribe, Obinna', 'Nguku, Patrick', 'Davis, Lora', 'Preacely, Nykiconia', 'Luce, Richard', 'Antara, Simon', 'Imara, Hiari', 'Ndjakani, Yassa', 'Doyle, Timothy', 'Espinosa, Yescenia', 'Kazambu, Ditu', 'Delissaint, Dieula', 'Ngulefac, John', 'Njenga, Kariuki']",Pan Afr Med J,,,True
360fb902fea73a294614ebd95276b59de868786c,PMC,High success and low mortality rates with non-invasive ventilation in influenza A H1N1 patients in a tertiary hospital,http://dx.doi.org/10.1186/1756-0500-4-375,PMC3224397,21955389,CC BY,"BACKGROUND: In 2009, an outbreak of respiratory illness caused by influenza A H1N1 virus occurred worldwide. Some patients required Intensive Care Unit (ICU) admission. The use of non-invasive ventilation (NIV) in these patients is controversial, as the aerosol dispersion may contaminate the environment and health-care co-workers. METHODS: Describe the respiratory profile, the mortality rate, and the benefit of using NIV in patients with confirmed diagnosis of influenza AH1N1 who were admitted in the ICU during the year 2009. RESULTS: A total of 1, 401 cases of influenza A H1N1 were confirmed in our hospital by real-time RT-PCR in 2009, and 20 patients were admitted to the ICU. The patients' ages ranged from 18 to 74 years (median of 42). Acute Respiratory Failure (ARF) was present in 70% of patients. The median Acute Physiology and Chronic Health Evaluation II score was 7 (range 7 to 25). Of the 14 patients who developed ARF, 85.7% needed NIV and 14% needed invasive MV at admission. Our success rate (41.6%) with NIV was higher than that described by others. The hospital mortality rate was 2.1%. When influenza A H1N1 arrived in Brazil, the disease was already on endemic alert in other countries. The population was already aware of the symptoms and the health-care system of the treatment. This allowed patients to be properly and promptly treated for influenza A H1N1, while health-care workers took protective measures to avoid contamination. CONCLUSION: In our study we found a high success and low mortality rates with non-invasive ventilation in patients with influenza A H1N1.",2011 Sep 28,"['Timenetsky, Karina T', 'Aquino, Silvia HCT', 'Saghabi, Cilene', 'Taniguchi, Corinne', 'Silvia, Claudia V', 'Correa, Luci', 'Marra, Alexandre R', 'Eid, Raquel AC', 'dos Santos, Oscar FP']",BMC Res Notes,,,True
6dbc1181175c5ce84c649469fc4e9a4c7b6b8f32,PMC,Preventing Airborne Disease Transmission: Review of Methods for Ventilation Design in Health Care Facilities,http://dx.doi.org/10.4061/2011/124064,PMC3226423,22162813,CC BY,"Health care facility ventilation design greatly affects disease transmission by aerosols. The desire to control infection in hospitals and at the same time to reduce their carbon footprint motivates the use of unconventional solutions for building design and associated control measures. This paper considers indoor sources and types of infectious aerosols, and pathogen viability and infectivity behaviors in response to environmental conditions. Aerosol dispersion, heat and mass transfer, deposition in the respiratory tract, and infection mechanisms are discussed, with an emphasis on experimental and modeling approaches. Key building design parameters are described that include types of ventilation systems (mixing, displacement, natural and hybrid), air exchange rate, temperature and relative humidity, air flow distribution structure, occupancy, engineered disinfection of air (filtration and UV radiation), and architectural programming (source and activity management) for health care facilities. The paper describes major findings and suggests future research needs in methods for ventilation design of health care facilities to prevent airborne infection risk.",2011 Nov 15,"['Aliabadi, Amir A.', 'Rogak, Steven N.', 'Bartlett, Karen H.', 'Green, Sheldon I.']",Adv Prev Med,,,True
2db670e443cdceb7fb2ff63b6331df5d12efef99,PMC,A Quantitative Method for the Specific Assessment of Caspase-6 Activity in Cell Culture,http://dx.doi.org/10.1371/journal.pone.0027680,PMC3226564,22140457,CC BY,"Aberrant activation of caspase-6 has recently emerged as a major contributor to the pathogeneses of neurodegenerative disorders such as Alzheimer's and Huntington disease. Commercially available assays to measure caspase-6 activity commonly use the VEID peptide as a substrate. However these methods are not well suited to specifically assess caspase-6 activity in the presence of other, confounding protease activities, as often encountered in cell and tissue samples. Here we report the development of a method that overcomes this limitation by using a protein substrate, lamin A, which is highly specific for caspase-6 cleavage at amino acid 230. Using a neo-epitope antibody against cleaved lamin A, we developed an electrochemiluminescence-based ELISA assay that is suitable to specifically detect and quantify caspase-6 activity in highly apoptotic cell extracts. The method is more sensitive than VEID-based assays and can be adapted to a high-content imaging platform for high-throughput screening. This method should be useful to screen for and characterize caspase-6 inhibitor compounds and other interventions to decrease intracellular caspase-6 activity for applications in neurodegenerative disorders.",2011 Nov 29,"['Ehrnhoefer, Dagmar E.', 'Skotte, Niels H.', 'Savill, Jane', 'Nguyen, Yen T. N.', 'Ladha, Safia', 'Cao, Li-Ping', 'Dullaghan, Edie', 'Hayden, Michael R.']",PLoS One,,,True
ea40bddad18086f300f45b71a07f3e4c14e060eb,PMC,Mapping of Minimal Motifs of B-Cell Epitopes on Human Zona Pellucida Glycoprotein-3,http://dx.doi.org/10.1155/2012/831010,PMC3227431,22162720,CC BY,"The human zona pellucida glycoprotein-3 (hZP3) by virtue of its critical role during fertilization has been proposed as a promising candidate antigen to develop a contraceptive vaccine. In this direction, it is imperative to map minimal motifs of the B cell epitopes (BCEs) so as to avoid ZP-specific oophoritogenic T cell epitopes (TCEs) in the ZP3-based immunogens. In this study, based on known results of mapping marmoset and bonnet monkey ZP3 (mstZP3 and bmZP3), two predictable epitopes(23–30 and 301–320) on hZP3 were first confirmed and five minimal motifs within four epitopes on hZP3 were defined using serum to recombinant hZP3a(22–176) or hZP3b(177–348) as well as a biosynthetic peptide strategy. These defined minimal motifs were QPLWLL(23–28) for hZP3(23–30), MQVTDD(103–108) for hZP3(93–110), EENW(178–181) for hZP3(172–190), as well as SNSWF(306–310) and EGP(313–315) for hZP3(301–320), respectively. Furthermore, the antigenicity of two peptides for hZP3(172–187) and hZP3(301–315) and specificity of the antibody response to these peptides were also evaluated, which produced high-titer antibodies in immunized animals that were capable of reacting to ZP on human oocytes, r-hZP3b(177–348) protein, as well as r-hZP3(172–190), r-hZP3(303–310), and r-hZP3(313–320) epitope peptides fused with truncated GST188 protein.",2012 Nov 17,"['Xu, Wan-Xiang', 'He, Ya-Ping', 'Wang, Jian', 'Tang, Hai-Ping', 'Shi, Hui-Juan', 'Sun, Xiao-Xi', 'Ji, Chao-Neng', 'Gu, Shao-Hua', 'Xie, Yi']",Clin Dev Immunol,,,True
6737b541bf9d5d5bbb80cc1dd06456f93dbcda72,PMC,Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection,http://dx.doi.org/10.1371/journal.pone.0027744,PMC3227585,22164200,CC BY,"Members of the Toll-like receptor (TLR) gene family occupy key roles in the mammalian innate immune system by functioning as sentries for the detection of invading pathogens, thereafter provoking host innate immune responses. We utilized a custom next-generation sequencing approach and allele-specific genotyping assays to detect and validate 280 biallelic variants across all 10 bovine TLR genes, including 71 nonsynonymous single nucleotide polymorphisms (SNPs) and one putative nonsense SNP. Bayesian haplotype reconstructions and median joining networks revealed haplotype sharing between Bos taurus taurus and Bos taurus indicus breeds at every locus, and specialized beef and dairy breeds could not be differentiated despite an average polymorphism density of 1 marker/158 bp. Collectively, 160 tagSNPs and two tag insertion-deletion mutations (indels) were sufficient to predict 100% of the variation at 280 variable sites for both Bos subspecies and their hybrids, whereas 118 tagSNPs and 1 tagIndel predictively captured 100% of the variation at 235 variable sites for B. t. taurus. Polyphen and SIFT analyses of amino acid (AA) replacements encoded by bovine TLR SNPs indicated that up to 32% of the AA substitutions were expected to impact protein function. Classical and newly developed tests of diversity provide strong support for balancing selection operating on TLR3 and TLR8, and purifying selection acting on TLR10. An investigation of the persistence and continuity of linkage disequilibrium (r(2)≥0.50) between adjacent variable sites also supported the presence of selection acting on TLR3 and TLR8. A case-control study employing validated variants from bovine TLR genes recognizing bacterial ligands revealed six SNPs potentially eliciting small effects on susceptibility to Mycobacterium avium spp paratuberculosis infection in dairy cattle. The results of this study will broadly impact domestic cattle research by providing the necessary foundation to explore several avenues of bovine translational genomics, and the potential for marker-assisted vaccination.",2011 Nov 30,"['Fisher, Colleen A.', 'Bhattarai, Eric K.', 'Osterstock, Jason B.', 'Dowd, Scot E.', 'Seabury, Paul M.', 'Vikram, Meenu', 'Whitlock, Robert H.', 'Schukken, Ynte H.', 'Schnabel, Robert D.', 'Taylor, Jeremy F.', 'Womack, James E.', 'Seabury, Christopher M.']",PLoS One,,,True
f56a6e854737649264b48f3709c54551d3660edd,PMC,"A Flavonoid, Luteolin, Cripples HIV-1 by Abrogation of Tat Function",http://dx.doi.org/10.1371/journal.pone.0027915,PMC3227592,22140483,CC BY,"Despite the effectiveness of combination antiretroviral treatment (cART) against HIV-1, evidence indicates that residual infection persists in different cell types. Intensification of cART does not decrease the residual viral load or immune activation. cART restricts the synthesis of infectious virus but does not curtail HIV-1 transcription and translation from either the integrated or unintegrated viral genomes in infected cells. All treated patients with full viral suppression actually have low-level viremia. More than 60% of treated individuals also develop minor HIV-1 –associated neurocognitive deficits (HAND) due to residual virus and immune activation. Thus, new therapeutic agents are needed to curtail HIV-1 transcription and residual virus. In this study, luteolin, a dietary supplement, profoundly reduced HIV-1 infection in reporter cells and primary lymphocytes. HIV-1inhibition by luteolin was independent of viral entry, as shown by the fact that wild-type and VSV–pseudotyped HIV-1 infections were similarly inhibited. Luteolin was unable to inhibit viral reverse transcription. Luteolin had antiviral activity in a latent HIV-1 reactivation model and effectively ablated both clade-B- and -C -Tat-driven LTR transactivation in reporter assays but had no effect on Tat expression and its sub-cellular localization. We conclude that luteolin confers anti–HIV-1 activity at the Tat functional level. Given its biosafety profile and ability to cross the blood-brain barrier, luteolin may serve as a base flavonoid to develop potent anti–HIV-1 derivatives to complement cART.",2011 Nov 30,"['Mehla, Rajeev', 'Bivalkar-Mehla, Shalmali', 'Chauhan, Ashok']",PLoS One,,,True
bcb10d6f9d4c95cfcd762fe6297dcb46bc15ec3f,PMC,Novel Inhibitor Design for Hemagglutinin against H1N1 Influenza Virus by Core Hopping Method,http://dx.doi.org/10.1371/journal.pone.0028111,PMC3227604,22140516,CC BY,"The worldwide spread of H1N1 avian influenza and the increasing reports about its resistance to the current drugs have made a high priority for developing new anti-influenza drugs. Owing to its unique function in assisting viruses to bind the cellular surface, a key step for them to subsequently penetrate into the infected cell, hemagglutinin (HA) has become one of the main targets for drug design against influenza virus. To develop potent HA inhibitors, the ZINC fragment database was searched for finding the optimal compound with the core hopping technique. As a result, the Neo6 compound was obtained. It has been shown through the subsequent molecular docking studies and molecular dynamic simulations that Neo6 not only assumes more favorable conformation at the binding pocket of HA but also has stronger binding interaction with its receptor. Accordingly, Neo6 may become a promising candidate for developing new and more powerful drugs for treating influenza. Or at the very least, the findings reported here may provide useful insights to stimulate new strategy in this area.",2011 Nov 30,"['Li, Xiao-Bo', 'Wang, Shu-Qing', 'Xu, Wei-Ren', 'Wang, Run-Ling', 'Chou, Kuo-Chen']",PLoS One,,,True
d92d00ed95878f5a37061b76e848fda5b11d21da,PMC,"Type I Interferon Reaction to Viral Infection in Interferon-Competent, Immortalized Cell Lines from the African Fruit Bat Eidolon helvum",http://dx.doi.org/10.1371/journal.pone.0028131,PMC3227611,22140523,CC BY,"Bats harbor several highly pathogenic zoonotic viruses including Rabies, Marburg, and henipaviruses, without overt clinical symptoms in the animals. It has been suspected that bats might have evolved particularly effective mechanisms to suppress viral replication. Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. helvum). Immortalized cell lines were generated; their potential to induce and react on IFN was confirmed, and biological assays were adapted to application in bat cell cultures, enabling comparison of landmark IFN properties with that of common mammalian cell lines. E. helvum cells were fully capable of reacting to viral and artificial IFN stimuli. E. helvum cells showed highest IFN mRNA induction, highly productive IFN protein secretion, and evidence of efficient IFN stimulated gene induction. In an Alphavirus infection model, O'nyong-nyong virus exhibited strong IFN induction but evaded the IFN response by translational rather than transcriptional shutoff, similar to other Alphavirus infections. These novel IFN-competent cell lines will allow comparative research on zoonotic, bat-borne viruses in order to model mechanisms of viral maintenance and emergence in bat reservoirs.",2011 Nov 30,"['Biesold, Susanne E.', 'Ritz, Daniel', 'Gloza-Rausch, Florian', 'Wollny, Robert', 'Drexler, Jan Felix', 'Corman, Victor M.', 'Kalko, Elisabeth K. V.', 'Oppong, Samuel', 'Drosten, Christian', 'Müller, Marcel A.']",PLoS One,,,True
15228615c1656f39a5ec8dcc8bc26ef0371d4040,PMC,Tamiflu-Resistant but HA-Mediated Cell-to-Cell Transmission through Apical Membranes of Cell-Associated Influenza Viruses,http://dx.doi.org/10.1371/journal.pone.0028178,PMC3227662,22140536,CC BY,"The infection of viruses to a neighboring cell is considered to be beneficial in terms of evasion from host anti-virus defense systems. There are two pathways for viral infection to “right next door”: one is the virus transmission through cell-cell fusion by forming syncytium without production of progeny virions, and the other is mediated by virions without virus diffusion, generally designated cell-to-cell transmission. Influenza viruses are believed to be transmitted as cell-free virus from infected cells to uninfected cells. Here, we demonstrated that influenza virus can utilize cell-to-cell transmission pathway through apical membranes, by handover of virions on the surface of an infected cell to adjacent host cells. Live cell imaging techniques showed that a recombinant influenza virus, in which the neuraminidase gene was replaced with the green fluorescence protein gene, spreads from an infected cell to adjacent cells forming infected cell clusters. This type of virus spreading requires HA activation by protease treatment. The cell-to-cell transmission was also blocked by amantadine, which inhibits the acidification of endosomes required for uncoating of influenza virus particles in endosomes, indicating that functional hemagglutinin and endosome acidification by M2 ion channel were essential for the cell-to-cell influenza virus transmission. Furthermore, in the cell-to-cell transmission of influenza virus, progeny virions could remain associated with the surface of infected cell even after budding, for the progeny virions to be passed on to adjacent uninfected cells. The evidence that cell-to-cell transmission occurs in influenza virus lead to the caution that local infection proceeds even when treated with neuraminidase inhibitors.",2011 Nov 30,"['Mori, Kotaro', 'Haruyama, Takahiro', 'Nagata, Kyosuke']",PLoS One,,,True
af06f5132b3178795ba440ec4f4949e9008c1737,PMC,It Takes a Community to Raise the Prevalence of a Zoonotic Pathogen,http://dx.doi.org/10.1155/2011/741406,PMC3228346,22162687,CC BY,"By definition, zoonotic pathogens are not strict host-species specialists in that they infect humans and at least one nonhuman reservoir species. The majority of zoonotic pathogens infect and are amplified by multiple vertebrate species in nature, each of which has a quantitatively different impact on the distribution and abundance of the pathogen and thus on disease risk. Unfortunately, when new zoonotic pathogens emerge, the dominant response by public health scientists is to search for a few, or even the single, most important reservoirs and to ignore other species that might strongly influence transmission. This focus on the single “primary” reservoir host species can delay biological understanding, and potentially public health interventions as species important in either amplifying or regulating the pathogen are overlooked. Investigating the evolutionary and ecological strategy of newly discovered or emerging pathogens within the community of potential and actual host species will be fruitful to both biological understanding and public health.",2011 Nov 21,"['Brisson, Dustin', 'Brinkley, Catherine', 'Humphrey, Parris T.', 'Kemps, Brian D.', 'Ostfeld, Richard S.']",Interdiscip Perspect Infect Dis,,,True
fbf1ce71db9a70babb5b4902d23438c1956125c6,PMC,Yeast Based Small Molecule Screen for Inhibitors of SARS-CoV,http://dx.doi.org/10.1371/journal.pone.0028479,PMC3229576,22164298,CC BY,"Severe acute respiratory coronavirus (SARS-CoV) emerged in 2002, resulting in roughly 8000 cases worldwide and 10% mortality. The animal reservoirs for SARS-CoV precursors still exist and the likelihood of future outbreaks in the human population is high. The SARS-CoV papain-like protease (PLP) is an attractive target for pharmaceutical development because it is essential for virus replication and is conserved among human coronaviruses. A yeast-based assay was established for PLP activity that relies on the ability of PLP to induce a pronounced slow-growth phenotype when expressed in S. cerevisiae. Induction of the slow-growth phenotype was shown to take place over a 60-hour time course, providing the basis for conducting a screen for small molecules that restore growth by inhibiting the function of PLP. Five chemical suppressors of the slow-growth phenotype were identified from the 2000 member NIH Diversity Set library. One of these, NSC158362, potently inhibited SARS-CoV replication in cell culture without toxic effects on cells, and it specifically inhibited SARS-CoV replication but not influenza virus replication. The effect of NSC158362 on PLP protease, deubiquitinase and anti-interferon activities was investigated but the compound did not alter these activities. Another suppressor, NSC158011, demonstrated the ability to inhibit PLP protease activity in a cell-based assay. The identification of these inhibitors demonstrated a strong functional connection between the PLP-based yeast assay, the inhibitory compounds, and SARS-CoV biology. Furthermore the data with NSC158362 suggest a novel mechanism for inhibition of SARS-CoV replication that may involve an unknown activity of PLP, or alternatively a direct effect on a cellular target that modifies or bypasses PLP function in yeast and mammalian cells.",2011 Dec 2,"['Frieman, Matthew', 'Basu, Dipanwita', 'Matthews, Krystal', 'Taylor, Justin', 'Jones, Grant', 'Pickles, Raymond', 'Baric, Ralph', 'Engel, Daniel A.']",PLoS One,,,True
a5df67ac88dab77c50c138cec2944814000c859f,PMC,Changes of Adult Population Health Status in China from 2003 to 2008,http://dx.doi.org/10.1371/journal.pone.0028411,PMC3229585,22164286,CC BY,"OBJECTIVES: The purpose of this study was to examine the change in health status of China's adult population between the years of 2003 and 2008 due to rapid economic growth and medical system improvement. METHODS: Data from the third and fourth Chinese national health services surveys covering 141,927 residents in 2003 and 136,371 residents in 2008 who were aged >18 years were analyzed. RESULTS: Chinese respondents in 2008 were more likely to report disease than in 2003. Smoking slightly decreased among men and women, and regular exercise showed much improvement. Stratified analyses revealed significant subpopulation disparities in rate ratios for 2008/2003 in the presence of chronic disease, with greater increases among women, elderly, the Han nationality, unmarried and widow, illiterate, rural, and regions east of China than other groups. CONCLUSIONS: Chinese adults in 2008 had worse health status than in 2003 in terms of presence of chronic disease. China's reform of health care will face more complex challenges in coming years from the deteriorating health status in Chinese adults.",2011 Dec 2,"['Sun, Hongpeng', 'Zhang, Qiuju', 'Luo, Xiao', 'Quan, Hude', 'Zhang, Feng', 'Liu, Chang', 'Liu, Meina']",PLoS One,,,True
523d27d193f6bd636b6fae4da4af51ea66907772,PMC,Persistent Expression of Hepatitis C Virus Non-Structural Proteins Leads to Increased Autophagy and Mitochondrial Injury in Human Hepatoma Cells,http://dx.doi.org/10.1371/journal.pone.0028551,PMC3229600,22164304,CC0,"HCV infection is a major cause of chronic liver disease and liver cancer in the United States. To address the pathogenesis caused by HCV infection, recent studies have focused on the direct cytopathic effects of individual HCV proteins, with the objective of identifying their specific roles in the overall pathogenesis. However, this approach precludes examination of the possible interactions between different HCV proteins and organelles. To obtain a better understanding of the various cytopathic effects of and cellular responses to HCV proteins, we used human hepatoma cells constitutively replicating HCV RNA encoding either the full-length polyprotein or the non-structural proteins, or cells constitutively expressing the structural protein core, to model the state of persistent HCV infection and examined the combination of various HCV proteins in cellular pathogenesis. Increased reactive oxygen species (ROS) generation in the mitochondria, mitochondrial injury and degeneration, and increased lipid accumulation were common among all HCV protein-expressing cells regardless of whether they expressed the structural or non-structural proteins. Expression of the non-structural proteins also led to increased oxidative stress in the cytosol, membrane blebbing in the endoplasmic reticulum, and accumulation of autophagocytic vacuoles. Alterations of cellular redox state, on the other hand, significantly changed the level of autophagy, suggesting a direct link between oxidative stress and HCV-mediated activation of autophagy. With the wide-spread cytopathic effects, cells with the full-length HCV polyprotein showed a modest antioxidant response and exhibited a significant increase in population doubling time and a concomitant decrease in cyclin D1. In contrast, cells expressing the non-structural proteins were able to launch a vigorous antioxidant response with up-regulation of antioxidant enzymes. The population doubling time and cyclin D1 level were also comparable to that of control cells. Finally, the cytopathic effects of core protein appeared to focus on the mitochondria without remarkable disturbances in the cytosol.",2011 Dec 2,"['Chu, Victor C.', 'Bhattacharya, Sayanti', 'Nomoto, Ann', 'Lin, Jiahui', 'Zaidi, Syed Kashif', 'Oberley, Terry D.', 'Weinman, Steven A.', 'Azhar, Salman', 'Huang, Ting-Ting']",PLoS One,,,True
9f5eb4cb37108793e2cf0ed3d5a68fea14620866,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,True
85445df68b35ea6813e73f82cf25be0e79f85984,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
c3b36cbef6bc5cbbd9ca8a7ce0d8581a3f7788c3,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,True
629da5ea7026f4f1a92b1a1bb0d2c2716e96ee57,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
9effda40334841573b2aa2600f56566a9faf71ff,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,True
e1a16106b7ace2c22c2958ba90cfe498efb9c509,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
7d0371cd505199c4f4f76e8884fcaf010a7fe3db,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
d96705b398373bfe34e6c4485a8482d89e37ff67,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
186bec5297ab7757c48f921af2ef1ae9f06780c3,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
0bd435718fed48d151e100eb0fc731d02c0adab6,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
e7358ff1cbb991ea673ffcd3ad13f067cc0fbb15,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
cea092fa779215010c8fafededcb5fab2b435a89,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
59c932b49a6498b87e3d43f42038cef789094b4d,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
03a9435da640ba52544a7b843acc359d3d98044e,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
a5bb10a841381a8c460e9127f0d66cbdf4f15248,PMC,Neighborhood Properties Are Important Determinants of Temperature Sensitive Mutations,http://dx.doi.org/10.1371/journal.pone.0028507,PMC3229608,22164302,CC BY,"Temperature-sensitive (TS) mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method–logistic regression–to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.",2011 Dec 2,"['Lockwood, Svetlana', 'Krishnamoorthy, Bala', 'Ye, Ping']",PLoS One,,,False
7f1f94a49e088244c897fd0bfc96de817d1b804a,PMC,Characterization of spontaneously generated prion-like conformers in cultured cells,,PMC3229973,21990137,CC BY,"A distinct conformational transition from the α-helix-rich cellular prion protein (PrP(C)) into its β-sheet-rich pathological isoform (PrP(Sc)) is the hallmark of prion diseases, a group of fatal transmissible encephalopathies that includes spontaneous and acquired forms. Recently, a PrP(Sc)-like intermediate form characterized by the formation of insoluble aggregates and protease-resistant PrP species termed insoluble PrP(C) (iPrP(C)) has been identified in uninfected mammalian brains and cultured neuronal cells, providing new insights into the molecular mechanism(s) of these diseases. Here, we explore the molecular characteristics of the spontaneously formed iPrP(C) in cultured neuroblastoma cells expressing wild-type or mutant human PrP linked to two familial prion diseases. We observed that although PrP mutation at either residue 183 from Thr to Ala (PrP(T183A)) or at residue 198 from Phe to Ser (PrP(F198S)) affects glycosylation at both N-linked glycosylation sites, the T183A mutation that results in intracellular retention significantly increased the formation of iPrP(C). Moreover, while autophagy is increased in F198S cells, it was significantly decreased in T183A cells. Our results indicate that iPrP(C) may be formed more readily in an intracellular compartment and that a significant increase in PrP(T183A) aggregation may be attributable to the inhibition of autophagy.",2011 Oct 9,"['Zou, Roger S.', 'Fujioka, Hisashi', 'Guo, Jian-Ping', 'Xiao, Xiangzhu', 'Shimoji, Miyuki', 'Kong, Crystal', 'Chen, Cecilia', 'Tasnadi, Megan', 'Voma, Chesinta', 'Yuan, Jue', 'Moudjou, Mohammed', 'Laude, Hubert', 'Petersen, Robert B.', 'Zou, Wen-Quan']",Aging (Albany NY),,,True
4aa19640fd1b1a8fc71b31d32fe6009c992bd767,PMC,Inhibition of Interferon Induction and Action by the Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus,http://dx.doi.org/10.1371/journal.pone.0028594,PMC3230622,22163042,CC BY,"The Nairoviruses are an important group of tick-borne viruses that includes pathogens of man (Crimean Congo hemorrhagic fever virus) and livestock animals (Dugbe virus, Nairobi sheep disease virus (NSDV)). NSDV is found in large parts of East Africa and the Indian subcontinent (where it is known as Ganjam virus). We have investigated the ability of NSDV to antagonise the induction and actions of interferon. Both pathogenic and apathogenic isolates could actively inhibit the induction of type 1 interferon, and also blocked the signalling pathways of both type 1 and type 2 interferons. Using transient expression of viral proteins or sections of viral proteins, these activities all mapped to the ovarian tumour-like protease domain (OTU) found in the viral RNA polymerase. Virus infection, or expression of this OTU domain in transfected cells, led to a great reduction in the incorporation of ubiquitin or ISG15 protein into host cell proteins. Point mutations in the OTU that inhibited the protease activity also prevented it from antagonising interferon induction and action. Interestingly, a mutation at a peripheral site, which had little apparent effect on the ability of the OTU to inhibit ubiquitination and ISG15ylation, removed the ability of the OTU to block the induction of type 1 and the action of type 2 interferons, but had a lesser effect on the ability to block type 1 interferon action, suggesting that targets other than ubiquitin and ISG15 may be involved in the actions of the viral OTU.",2011 Dec 5,"['Holzer, Barbara', 'Bakshi, Siddharth', 'Bridgen, Anne', 'Baron, Michael D.']",PLoS One,,,True
ab15d5ebce1f5f7cf0e689d32a55701e9e8fcde3,PMC,A Human Monoclonal Antibody with Neutralizing Activity against Highly Divergent Influenza Subtypes,http://dx.doi.org/10.1371/journal.pone.0028001,PMC3230632,22162996,CC0,"The interest in broad-range anti-influenza A monoclonal antibodies (mAbs) has recently been strengthened by the identification of anti-hemagglutinin (HA) mAbs endowed with heterosubtypic neutralizing activity to be used in the design of “universal” prophylactic or therapeutic tools. However, the majority of the single mAbs described to date do not bind and neutralize viral isolates belonging to highly divergent subtypes clustering into the two different HA-based influenza phylogenetic groups: the group 1 including, among others, subtypes H1, H2, H5 and H9 and the group 2 including, among others, H3 subtype. Here, we describe a human mAb, named PN-SIA28, capable of binding and neutralizing all tested isolates belonging to phylogenetic group 1, including H1N1, H2N2, H5N1 and H9N2 subtypes and several isolates belonging to group 2, including H3N2 isolates from the first period of the 1968 pandemic. Therefore, PN-SIA28 is capable of neutralizing isolates belonging to subtypes responsible of all the reported pandemics, as well as other subtypes with pandemic potential. The region recognized by PN-SIA28 has been identified on the stem region of HA and includes residues highly conserved among the different influenza subtypes. A deep characterization of PN-SIA28 features may represent a useful help in the improvement of available anti-influenza therapeutic strategies and can provide new tools for the development of universal vaccinal strategies.",2011 Dec 5,"['Clementi, Nicola', 'De Marco, Donata', 'Mancini, Nicasio', 'Solforosi, Laura', 'Moreno, Guisella J.', 'Gubareva, Larisa V.', 'Mishin, Vasiliy', 'Di Pietro, Andrea', 'Vicenzi, Elisa', 'Siccardi, Antonio G.', 'Clementi, Massimo', 'Burioni, Roberto']",PLoS One,,,True
b61d4d87ea3b4fa2ff058ee867bdac4f15c0cf11,PMC,Stress Granules in the Viral Replication Cycle,http://dx.doi.org/10.3390/v3112328,PMC3230854,22163347,CC BY,"As intracellular parasites, viruses require a host cell in order to replicate. However, they face a series of cellular responses against infection. One of these responses is the activation of the double-stranded RNA (dsRNA)-activated protein kinase R (PKR). PKR phosphorylates the α subunit of eukaryotic translation initiation factor 2 (eIF2α), which in turn results in global protein synthesis inhibition and formation of stress granules (SGs). Recent studies have shown that SGs can interfere with the replicative cycle of certain viruses. This review addresses how viruses have evolved different control strategies at the SG level to ensure an efficient replication cycle during the cellular stress response triggered by the viral infection.",2011 Nov 18,"['Montero, Hilda', 'Trujillo-Alonso, Vicenta']",Viruses,,,True
c7fbc3c2ef9549d8a6531237b2e9d09cf09a6567,PMC,Microfluidics-Based Lab-on-Chip Systems in DNA-Based Biosensing: An Overview,http://dx.doi.org/10.3390/s110605754,PMC3231440,22163925,CC BY,"Microfluidics-based lab-on-chip (LOC) systems are an active research area that is revolutionising high-throughput sequencing for the fast, sensitive and accurate detection of a variety of pathogens. LOCs also serve as portable diagnostic tools. The devices provide optimum control of nanolitre volumes of fluids and integrate various bioassay operations that allow the devices to rapidly sense pathogenic threat agents for environmental monitoring. LOC systems, such as microfluidic biochips, offer advantages compared to conventional identification procedures that are tedious, expensive and time consuming. This paper aims to provide a broad overview of the need for devices that are easy to operate, sensitive, fast, portable and sufficiently reliable to be used as complementary tools for the control of pathogenic agents that damage the environment.",2011 May 27,"['Dutse, Sabo Wada', 'Yusof, Nor Azah']",Sensors (Basel),,,True
2f855365da2675234802a5f218bda88aacc089b7,PMC,Lactococci and lactobacilli as mucosal delivery vectors for therapeutic proteins and DNA vaccines,http://dx.doi.org/10.1186/1475-2859-10-S1-S4,PMC3231930,21995317,CC BY,"Food-grade Lactic Acid Bacteria (LAB) have been safely consumed for centuries by humans in fermented foods. Thus, they are good candidates to develop novel oral vectors, constituting attractive alternatives to attenuated pathogens, for mucosal delivery strategies. Herein, this review summarizes our research, up until now, on the use of LAB as mucosal delivery vectors for therapeutic proteins and DNA vaccines. Most of our work has been based on the model LAB Lactococcus lactis, for which we have developed efficient genetic tools, including expression signals and host strains, for the heterologous expression of therapeutic proteins such as antigens, cytokines and enzymes. Resulting recombinant lactococci strains have been tested successfully for their prophylactic and therapeutic effects in different animal models: i) against human papillomavirus type 16 (HPV-16)-induced tumors in mice, ii) to partially prevent a bovine β-lactoglobulin (BLG)-allergic reaction in mice and iii) to regulate body weight and food consumption in obese mice. Strikingly, all of these tools have been successfully transposed to the Lactobacillus genus, in recent years, within our laboratory. Notably, anti-oxidative Lactobacillus casei strains were constructed and tested in two chemically-induced colitis models. In parallel, we also developed a strategy based on the use of L. lactis to deliver DNA at the mucosal level, and were able to show that L. lactis is able to modulate the host response through DNA delivery. Today, we consider that all of our consistent data, together with those obtained by other groups, demonstrate and reinforce the interest of using LAB, particularly lactococci and lactobacilli strains, to develop novel therapeutic protein mucosal delivery vectors which should be tested now in human clinical trials.",2011 Aug 30,"['Bermúdez-Humarán, Luis G', 'Kharrat, Pascale', 'Chatel, Jean-Marc', 'Langella, Philippe']",Microb Cell Fact,,,True
f18afbc0a4621e7f13dcfbc67c85bf8dfe3b30ea,PMC,Tissue Tropism and Target Cells of NSs-Deleted Rift Valley Fever Virus in Live Immunodeficient Mice,http://dx.doi.org/10.1371/journal.pntd.0001421,PMC3232203,22163058,CC BY,"BACKGROUND: Rift Valley fever virus (RVFV) causes disease in livestock and humans. It can be transmitted by mosquitoes, inhalation or physical contact with the body fluids of infected animals. Severe clinical cases are characterized by acute hepatitis with hemorrhage, meningoencephalitis and/or retinitis. The dynamics of RVFV infection and the cell types infected in vivo are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: RVFV strains expressing humanized Renilla luciferase (hRLuc) or green fluorescent protein (GFP) were generated and inoculated to susceptible Ifnar1-deficient mice. We investigated the tissue tropism in these mice and the nature of the target cells in vivo using whole-organ imaging and flow cytometry. After intraperitoneal inoculation, hRLuc signal was observed primarily in the thymus, spleen and liver. Macrophages infiltrating various tissues, in particular the adipose tissue surrounding the pancreas also expressed the virus. The liver rapidly turned into the major luminescent organ and the mice succumbed to severe hepatitis. The brain remained weakly luminescent throughout infection. FACS analysis in RVFV-GFP-infected mice showed that the macrophages, dendritic cells and granulocytes were main target cells for RVFV. The crucial role of cells of the monocyte/macrophage/dendritic lineage during RVFV infection was confirmed by the slower viral dissemination, decrease in RVFV titers in blood, and prolonged survival of macrophage- and dendritic cell-depleted mice following treatment with clodronate liposomes. Upon dermal and nasal inoculations, the viral dissemination was primarily observed in the lymph node draining the injected ear and in the lungs respectively, with a significant increase in survival time. CONCLUSIONS/SIGNIFICANCE: These findings reveal the high levels of phagocytic cells harboring RVFV during viral infection in Ifnar1-deficient mice. They demonstrate that bioluminescent and fluorescent viruses can shed new light into the pathogenesis of RVFV infection.",2011 Dec 6,"['Gommet, Céline', 'Billecocq, Agnès', 'Jouvion, Grégory', 'Hasan, Milena', 'Zaverucha do Valle, Tânia', 'Guillemot, Laurent', 'Blanchet, Charlène', 'van Rooijen, Nico', 'Montagutelli, Xavier', 'Bouloy, Michèle', 'Panthier, Jean-Jacques']",PLoS Negl Trop Dis,,,True
3ea132bf32c7717caf9e57fd48e116eed79697b1,PMC,Phages Bearing Affinity Peptides to Bovine Rotavirus Differentiate the Virus from Other Viruses,http://dx.doi.org/10.1371/journal.pone.0028667,PMC3232237,22163050,CC BY,"The aim of this study was to identify potential ligands and develop a novel diagnostic test to pathogenic bovine rotavirus (BRV) using phage display technology. The viruses were used as an immobilized target followed by incubation with a 12-mer phage display random peptide library. After five rounds of biopanning, phages had a specific binding activity to BRV were isolated. DNA sequencing indicated that phage displayed peptides HVHPPLRPHSDK, HATNHLPTPHNR or YPTHHAHTTPVR were potential ligands to BRV. Using the specific peptide-expressing phages, we developed a phage-based ELISA to differentiate BRV from other viruses. Compared with quantitative real-time PCR (qPCR), the phage-mediated ELISA was more suitable for the capture of BRV and the detection limitation of this approach was 0.1 µg/ml of samples. The high sensitivity, specificity and low cross-reactivity for the phage-based ELISA were confirmed in receiver operating characteristics (ROC) analysis.",2011 Dec 6,"['Wang, Xin', 'Li, Guangxing', 'Ren, Yudong', 'Ren, Xiaofeng']",PLoS One,,,True
cd21b40d05f66d9cc280d65928651c4552ad8fdd,PMC,Evaluation of Internal Reference Genes for Quantitative Expression Analysis by Real-Time PCR in Ovine Whole Blood,http://dx.doi.org/10.3390/ijms12117732,PMC3233434,22174628,CC BY,"The use of reference genes is commonly accepted as the most reliable approach to normalize qRT-PCR and to reduce possible errors in the quantification of gene expression. The most suitable reference genes in sheep have been identified for a restricted range of tissues, but no specific data on whole blood are available. The aim of this study was to identify a set of reference genes for normalizing qRT-PCR from ovine whole blood. We designed 11 PCR assays for commonly employed reference genes belonging to various functional classes and then determined their expression stability in whole blood samples from control and disease-stressed sheep. SDHA and YWHAZ were considered the most suitable internal controls as they were stably expressed regardless of disease status according to both geNorm and NormFinder software; furthermore, geNorm indicated SDHA/HPRT, YWHAZ/GAPDH and SDHA/YWHAZ as the best reference gene combinations in control, disease-stressed and combined sheep groups, respectively. Our study provides a validated panel of optimal control genes which may be useful for the identification of genes differentially expressed by qRT-PCR in a readily accessible tissue, with potential for discovering new physiological and disease markers and as a tool to improve production traits (e.g., by identifying expression Quantitative Trait Loci). An additional outcome of the study is a set of intron-spanning primer sequences suitable for gene expression experiments employing SYBR Green chemistry on other ovine tissues and cells.",2011 Nov 9,"['Peletto, Simone', 'Bertuzzi, Simone', 'Campanella, Chiara', 'Modesto, Paola', 'Maniaci, Maria Grazia', 'Bellino, Claudio', 'Ariello, Dario', 'Quasso, Antonio', 'Caramelli, Maria', 'Acutis, Pier Luigi']",Int J Mol Sci,,,True
c3c131a47ced4db370181524292fac5627fb6389,PMC,Applications of Next-Generation Sequencing Technologies to Diagnostic Virology,http://dx.doi.org/10.3390/ijms12117861,PMC3233444,22174638,CC BY,"Novel DNA sequencing techniques, referred to as “next-generation” sequencing (NGS), provide high speed and throughput that can produce an enormous volume of sequences with many possible applications in research and diagnostic settings. In this article, we provide an overview of the many applications of NGS in diagnostic virology. NGS techniques have been used for high-throughput whole viral genome sequencing, such as sequencing of new influenza viruses, for detection of viral genome variability and evolution within the host, such as investigation of human immunodeficiency virus and human hepatitis C virus quasispecies, and monitoring of low-abundance antiviral drug-resistance mutations. NGS techniques have been applied to metagenomics-based strategies for the detection of unexpected disease-associated viruses and for the discovery of novel human viruses, including cancer-related viruses. Finally, the human virome in healthy and disease conditions has been described by NGS-based metagenomics.",2011 Nov 14,"['Barzon, Luisa', 'Lavezzo, Enrico', 'Militello, Valentina', 'Toppo, Stefano', 'Palù, Giorgio']",Int J Mol Sci,,,True
58d91841094c91e8269b22337c66dfa16e04b965,PMC,Norovirus Regulation of the Innate Immune Response and Apoptosis Occurs via the Product of the Alternative Open Reading Frame 4,http://dx.doi.org/10.1371/journal.ppat.1002413,PMC3234229,22174679,CC BY,"Small RNA viruses have evolved many mechanisms to increase the capacity of their short genomes. Here we describe the identification and characterization of a novel open reading frame (ORF4) encoded by the murine norovirus (MNV) subgenomic RNA, in an alternative reading frame overlapping the VP1 coding region. ORF4 is translated during virus infection and the resultant protein localizes predominantly to the mitochondria. Using reverse genetics we demonstrated that expression of ORF4 is not required for virus replication in tissue culture but its loss results in a fitness cost since viruses lacking the ability to express ORF4 restore expression upon repeated passage in tissue culture. Functional analysis indicated that the protein produced from ORF4 antagonizes the innate immune response to infection by delaying the upregulation of a number of cellular genes activated by the innate pathway, including IFN-Beta. Apoptosis in the RAW264.7 macrophage cell line was also increased during virus infection in the absence of ORF4 expression. In vivo analysis of the WT and mutant virus lacking the ability to express ORF4 demonstrated an important role for ORF4 expression in infection and virulence. STAT1-/- mice infected with a virus lacking the ability to express ORF4 showed a delay in the onset of clinical signs when compared to mice infected with WT virus. Quantitative PCR and histopathological analysis of samples from these infected mice demonstrated that infection with a virus not expressing ORF4 results in a delayed infection in this system. In light of these findings we propose the name virulence factor 1, VF1 for this protein. The identification of VF1 represents the first characterization of an alternative open reading frame protein for the calicivirus family. The immune regulatory function of the MNV VF1 protein provide important perspectives for future research into norovirus biology and pathogenesis.",2011 Dec 8,"['McFadden, Nora', 'Bailey, Dalan', 'Carrara, Guia', 'Benson, Alicia', 'Chaudhry, Yasmin', 'Shortland, Amita', 'Heeney, Jonathan', 'Yarovinsky, Felix', 'Simmonds, Peter', 'Macdonald, Andrew', 'Goodfellow, Ian']",PLoS Pathog,,,True
3e3925148a778080ac13f3f532ee63ae24a3d1e5,PMC,Sequential Adaptive Mutations Enhance Efficient Vector Switching by Chikungunya Virus and Its Epidemic Emergence,http://dx.doi.org/10.1371/journal.ppat.1002412,PMC3234230,22174678,CC BY,"The adaptation of Chikungunya virus (CHIKV) to a new vector, the Aedes albopictus mosquito, is a major factor contributing to its ongoing re-emergence in a series of large-scale epidemics of arthritic disease in many parts of the world since 2004. Although the initial step of CHIKV adaptation to A. albopictus was determined to involve an A226V amino acid substitution in the E1 envelope glycoprotein that first arose in 2005, little attention has been paid to subsequent CHIKV evolution after this adaptive mutation was convergently selected in several geographic locations. To determine whether selection of second-step adaptive mutations in CHIKV or other arthropod-borne viruses occurs in nature, we tested the effect of an additional envelope glycoprotein amino acid change identified in Kerala, India in 2009. This substitution, E2-L210Q, caused a significant increase in the ability of CHIKV to develop a disseminated infection in A. albopictus, but had no effect on CHIKV fitness in the alternative mosquito vector, A. aegypti, or in vertebrate cell lines. Using infectious viruses or virus-like replicon particles expressing the E2-210Q and E2-210L residues, we determined that E2-L210Q acts primarily at the level of infection of A. albopictus midgut epithelial cells. In addition, we observed that the initial adaptive substitution, E1-A226V, had a significantly stronger effect on CHIKV fitness in A. albopictus than E2-L210Q, thus explaining the observed time differences required for selective sweeps of these mutations in nature. These results indicate that the continuous CHIKV circulation in an A. albopictus-human cycle since 2005 has resulted in the selection of an additional, second-step mutation that may facilitate even more efficient virus circulation and persistence in endemic areas, further increasing the risk of more severe and expanded CHIK epidemics.",2011 Dec 8,"['Tsetsarkin, Konstantin A.', 'Weaver, Scott C.']",PLoS Pathog,,,True
8792b598db3c64a2da937a9cefc989a7fd0a67aa,PMC,Multifaceted Regulation of Translational Readthrough by RNA Replication Elements in a Tombusvirus,http://dx.doi.org/10.1371/journal.ppat.1002423,PMC3234231,22174683,CC BY,"Translational readthrough of stop codons by ribosomes is a recoding event used by a variety of viruses, including plus-strand RNA tombusviruses. Translation of the viral RNA-dependent RNA polymerase (RdRp) in tombusviruses is mediated using this strategy and we have investigated this process using a variety of in vitro and in vivo approaches. Our results indicate that readthrough generating the RdRp requires a novel long-range RNA-RNA interaction, spanning a distance of ∼3.5 kb, which occurs between a large RNA stem-loop located 3'-proximal to the stop codon and an RNA replication structure termed RIV at the 3'-end of the viral genome. Interestingly, this long-distance RNA-RNA interaction is modulated by mutually-exclusive RNA structures in RIV that represent a type of RNA switch. Moreover, a different long-range RNA-RNA interaction that was previously shown to be necessary for viral RNA replicase assembly was also required for efficient readthrough production of the RdRp. Accordingly, multiple replication-associated RNA elements are involved in modulating the readthrough event in tombusviruses and we propose an integrated mechanistic model to describe how this regulatory network could be advantageous by (i) providing a quality control system for culling truncated viral genomes at an early stage in the replication process, (ii) mediating cis-preferential replication of viral genomes, and (iii) coordinating translational readthrough of the RdRp with viral genome replication. Based on comparative sequence analysis and experimental data, basic elements of this regulatory model extend to other members of Tombusviridae, as well as to viruses outside of this family.",2011 Dec 8,"['Cimino, Peter A.', 'Nicholson, Beth L.', 'Wu, Baodong', 'Xu, Wei', 'White, K. Andrew']",PLoS Pathog,,,True
5620946d8f3bbeeed801a931baa135ee4dd65176,PMC,SARS Coronavirus nsp1 Protein Induces Template-Dependent Endonucleolytic Cleavage of mRNAs: Viral mRNAs Are Resistant to nsp1-Induced RNA Cleavage,http://dx.doi.org/10.1371/journal.ppat.1002433,PMC3234236,22174690,CC BY,"SARS coronavirus (SCoV) nonstructural protein (nsp) 1, a potent inhibitor of host gene expression, possesses a unique mode of action: it binds to 40S ribosomes to inactivate their translation functions and induces host mRNA degradation. Our previous study demonstrated that nsp1 induces RNA modification near the 5′-end of a reporter mRNA having a short 5′ untranslated region and RNA cleavage in the encephalomyocarditis virus internal ribosome entry site (IRES) region of a dicistronic RNA template, but not in those IRES elements from hepatitis C or cricket paralysis viruses. By using primarily cell-free, in vitro translation systems, the present study revealed that the nsp1 induced endonucleolytic RNA cleavage mainly near the 5′ untranslated region of capped mRNA templates. Experiments using dicistronic mRNAs carrying different IRESes showed that nsp1 induced endonucleolytic RNA cleavage within the ribosome loading region of type I and type II picornavirus IRES elements, but not that of classical swine fever virus IRES, which is characterized as a hepatitis C virus-like IRES. The nsp1-induced RNA cleavage of template mRNAs exhibited no apparent preference for a specific nucleotide sequence at the RNA cleavage sites. Remarkably, SCoV mRNAs, which have a 5′ cap structure and 3′ poly A tail like those of typical host mRNAs, were not susceptible to nsp1-mediated RNA cleavage and importantly, the presence of the 5′-end leader sequence protected the SCoV mRNAs from nsp1-induced endonucleolytic RNA cleavage. The escape of viral mRNAs from nsp1-induced RNA cleavage may be an important strategy by which the virus circumvents the action of nsp1 leading to the efficient accumulation of viral mRNAs and viral proteins during infection.",2011 Dec 8,"['Huang, Cheng', 'Lokugamage, Kumari G.', 'Rozovics, Janet M.', 'Narayanan, Krishna', 'Semler, Bert L.', 'Makino, Shinji']",PLoS Pathog,,,True
be1d63805272f9d58e200bf0a8b57e8136b30af4,PMC,Identifying Hosts of Families of Viruses: A Machine Learning Approach,http://dx.doi.org/10.1371/journal.pone.0027631,PMC3235098,22174744,CC BY,"Identifying emerging viral pathogens and characterizing their transmission is essential to developing effective public health measures in response to an epidemic. Phylogenetics, though currently the most popular tool used to characterize the likely host of a virus, can be ambiguous when studying species very distant to known species and when there is very little reliable sequence information available in the early stages of the outbreak of disease. Motivated by an existing framework for representing biological sequence information, we learn sparse, tree-structured models, built from decision rules based on subsequences, to predict viral hosts from protein sequence data using popular discriminative machine learning tools. Furthermore, the predictive motifs robustly selected by the learning algorithm are found to show strong host-specificity and occur in highly conserved regions of the viral proteome.",2011 Dec 9,"['Raj, Anil', 'Dewar, Michael', 'Palacios, Gustavo', 'Rabadan, Raul', 'Wiggins, Christopher H.']",PLoS One,,,True
1ff54c023f5b659d36e7f00e9b853e548e3f2875,PMC,Identifying Hosts of Families of Viruses: A Machine Learning Approach,http://dx.doi.org/10.1371/journal.pone.0027631,PMC3235098,22174744,CC BY,"Identifying emerging viral pathogens and characterizing their transmission is essential to developing effective public health measures in response to an epidemic. Phylogenetics, though currently the most popular tool used to characterize the likely host of a virus, can be ambiguous when studying species very distant to known species and when there is very little reliable sequence information available in the early stages of the outbreak of disease. Motivated by an existing framework for representing biological sequence information, we learn sparse, tree-structured models, built from decision rules based on subsequences, to predict viral hosts from protein sequence data using popular discriminative machine learning tools. Furthermore, the predictive motifs robustly selected by the learning algorithm are found to show strong host-specificity and occur in highly conserved regions of the viral proteome.",2011 Dec 9,"['Raj, Anil', 'Dewar, Michael', 'Palacios, Gustavo', 'Rabadan, Raul', 'Wiggins, Christopher H.']",PLoS One,,,False
295415768cd300ee4e31ab6d8988ed15b0b25815,PMC,Identifying Hosts of Families of Viruses: A Machine Learning Approach,http://dx.doi.org/10.1371/journal.pone.0027631,PMC3235098,22174744,CC BY,"Identifying emerging viral pathogens and characterizing their transmission is essential to developing effective public health measures in response to an epidemic. Phylogenetics, though currently the most popular tool used to characterize the likely host of a virus, can be ambiguous when studying species very distant to known species and when there is very little reliable sequence information available in the early stages of the outbreak of disease. Motivated by an existing framework for representing biological sequence information, we learn sparse, tree-structured models, built from decision rules based on subsequences, to predict viral hosts from protein sequence data using popular discriminative machine learning tools. Furthermore, the predictive motifs robustly selected by the learning algorithm are found to show strong host-specificity and occur in highly conserved regions of the viral proteome.",2011 Dec 9,"['Raj, Anil', 'Dewar, Michael', 'Palacios, Gustavo', 'Rabadan, Raul', 'Wiggins, Christopher H.']",PLoS One,,,False
35593b9b140bf1c91c758584ed4e924dd7798436,PMC,Cochrane Systematic Reviews of Chinese Herbal Medicines: An Overview,http://dx.doi.org/10.1371/journal.pone.0028696,PMC3235143,22174870,CC BY,"OBJECTIVES: Our study had two objectives: a) to systematically identify all existing systematic reviews of Chinese herbal medicines (CHM) published in Cochrane Library; b) to assess the methodological quality of included reviews. METHODOLOGY/PRINCIPAL FINDINGS: We performed a systematic search of the Cochrane Database of Systematic Reviews (CDSR, Issue 5, 2010) to identify all reviews of CHM. A total of fifty-eight reviews were eligible for our study. Twenty-one of the included reviews had at least one Traditional Chinese Medicine (TCM) practitioner as its co-author. 7 reviews didn't include any primary study, the remaining reviews (n = 51) included a median of 9 studies and 936 participants. 50% of reviews were last assessed as up-to-date prior to 2008. The questions addressed by 39 reviews were broad in scope, in which 9 reviews combined studies with different herbal medicines. For OQAQ, the mean of overall quality score (item 10) was 5.05 (95% CI; 4.58-5.52). All reviews assessed the methodological quality of primary studies, 16% of included primary studies used adequate sequence generation and 7% used adequate allocation concealment. Of the 51 nonempty reviews, 23 reviews were reported as being inconclusive, while 27 concluded that there might be benefit of CHM, which was limited by the poor quality or inadequate quantity of included studies. 58 reviews reported searching a median of seven electronic databases, while 10 reviews did not search any Chinese database. CONCLUSIONS: Now CDSR has included large numbers of CHM reviews, our study identified some areas which could be improved, such as almost half of included reviews did not have the participation of TCM practitioners and were not up-to-date according to Cochrane criteria, some reviews pooled the results of different herbal medicines and ignored the searching of Chinese databases.",2011 Dec 9,"['Hu, Jing', 'Zhang, Junhua', 'Zhao, Wei', 'Zhang, Yongling', 'Zhang, Li', 'Shang, Hongcai']",PLoS One,,,True
3941bfed937029a31746847f195aeb98631f8d0d,PMC,Function of Membrane Rafts in Viral Lifecycles and Host Cellular Response,http://dx.doi.org/10.1155/2011/245090,PMC3235436,22191032,CC BY,"Membrane rafts are small (10–200 nm) sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Membrane rafts play an important role in viral infection cycles and viral virulence. Viruses are divided into four main classes, enveloped DNA virus, enveloped RNA virus, nonenveloped DNA virus, and nonenveloped RNA virus. General virus infection cycle is also classified into two sections, the early stage (entry process) and the late stage (assembly, budding, and release processes of virus particles). In the viral cycle, membrane rafts act as a scaffold of many cellular signal transductions, which are associated with symptoms caused by viral infections. In this paper, we describe the functions of membrane rafts in viral lifecycles and host cellular response according to each virus classification, each stage of the virus lifecycle, and each virus-induced signal transduction.",2011 Dec 7,"['Takahashi, Tadanobu', 'Suzuki, Takashi']",Biochem Res Int,,,True
8856e1f2644acc2d51c57d3ead6dd14a929a014b,PMC,Interferon Lambda: A New Sword in Cancer Immunotherapy,http://dx.doi.org/10.1155/2011/349575,PMC3235441,22190970,CC BY,"The discovery of the interferon-lambda (IFN-λ) family has considerably contributed to our understanding of the role of interferon not only in viral infections but also in cancer. IFN-λ proteins belong to the new type III IFN group. Type III IFN is structurally similar to type II IFN (IFN-γ) but functionally identical to type I IFN (IFN-α/β). However, in contrast to type I or type II IFNs, the response to type III IFN is highly cell-type specific. Only epithelial-like cells and to a lesser extent some immune cells respond to IFN-λ. This particular pattern of response is controlled by the differential expression of the IFN-λ receptor, which, in contrast to IFN-α, should result in limited side effects in patients. Recently, we and other groups have shown in several animal models a potent antitumor role of IFN-λ that will open a new challenging era for the current IFN therapy.",2011 Dec 6,"['Lasfar, Ahmed', 'Abushahba, Walid', 'Balan, Murugabaskar', 'Cohen-Solal, Karine A.']",Clin Dev Immunol,,,True
12bc88e7428c240181f181ca0358dac85ae16289,PMC,Current Status of the Immunomodulation and Immunomediated Therapeutic Strategies for Multiple Sclerosis,http://dx.doi.org/10.1155/2012/970789,PMC3235500,22203863,CC BY,"Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and CD4(+) T cells form the core immunopathogenic cascade leading to chronic inflammation. Traditionally, Th1 cells (interferon-γ-producing CD4(+) T cells) driven by interleukin 12 (IL12) were considered to be the encephalitogenic T cells in MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Currently, Th17 cells (Il17-producing CD4(+) T cells) are considered to play a fundamental role in the immunopathogenesis of EAE. This paper highlights the growing evidence that Th17 cells play the core role in the complex adaptive immunity of EAE/MS and discusses the roles of the associated immune cells and cytokines. These constitute the modern immunological basis for the development of novel clinical and preclinical immunomodulatory therapies for MS discussed in this paper.",2012 Dec 6,"['Chen, Shyi-Jou', 'Wang, Yen-Ling', 'Fan, Hueng-Chuen', 'Lo, Wen-Tsung', 'Wang, Chih-Chien', 'Sytwu, Huey-Kang']",Clin Dev Immunol,,,True
b56324b4de371913188d3eae4437eaaeda3b814b,PMC,Long-Term Prediction of Emergency Department Revenue and Visitor Volume Using Autoregressive Integrated Moving Average Model,http://dx.doi.org/10.1155/2011/395690,PMC3235663,22203886,CC BY,"This study analyzed meteorological, clinical and economic factors in terms of their effects on monthly ED revenue and visitor volume. Monthly data from January 1, 2005 to September 30, 2009 were analyzed. Spearman correlation and cross-correlation analyses were performed to identify the correlation between each independent variable, ED revenue, and visitor volume. Autoregressive integrated moving average (ARIMA) model was used to quantify the relationship between each independent variable, ED revenue, and visitor volume. The accuracies were evaluated by comparing model forecasts to actual values with mean absolute percentage of error. Sensitivity of prediction errors to model training time was also evaluated. The ARIMA models indicated that mean maximum temperature, relative humidity, rainfall, non-trauma, and trauma visits may correlate positively with ED revenue, but mean minimum temperature may correlate negatively with ED revenue. Moreover, mean minimum temperature and stock market index fluctuation may correlate positively with trauma visitor volume. Mean maximum temperature, relative humidity and stock market index fluctuation may correlate positively with non-trauma visitor volume. Mean maximum temperature and relative humidity may correlate positively with pediatric visitor volume, but mean minimum temperature may correlate negatively with pediatric visitor volume. The model also performed well in forecasting revenue and visitor volume.",2011 Dec 4,"['Chen, Chieh-Fan', 'Ho, Wen-Hsien', 'Chou, Huei-Yin', 'Yang, Shu-Mei', 'Chen, I-Te', 'Shi, Hon-Yi']",Comput Math Methods Med,,,True
c405097039f3cfefa4c6cf436925d3e3c8c3e013,PMC,"Culling-Induced Changes in Badger (Meles meles) Behaviour, Social Organisation and the Epidemiology of Bovine Tuberculosis",http://dx.doi.org/10.1371/journal.pone.0028904,PMC3237560,22194946,CC BY,"In the UK, attempts since the 1970s to control the incidence of bovine tuberculosis (bTB) in cattle by culling a wildlife host, the European badger (Meles meles), have produced equivocal results. Culling-induced social perturbation of badger populations may lead to unexpected outcomes. We test predictions from the ‘perturbation hypothesis’, determining the impact of culling operations on badger populations, movement of surviving individuals and the influence on the epidemiology of bTB in badgers using data dervied from two study areas within the UK Government's Randomised Badger Culling Trial (RBCT). Culling operations did not remove all individuals from setts, with between 34–43% of badgers removed from targeted social groups. After culling, bTB prevalence increased in badger social groups neighbouring removals, particularly amongst cubs. Seventy individual adult badgers were fitted with radio-collars, yielding 8,311 locational fixes from both sites between November 2001 and December 2003. Home range areas of animals surviving within removed groups increased by 43.5% in response to culling. Overlap between summer ranges of individuals from Neighbouring social groups in the treatment population increased by 73.3% in response to culling. The movement rate of individuals between social groups was low, but increased after culling, in Removed and Neighbouring social groups. Increased bTB prevalence in Neighbouring groups was associated with badger movements both into and out of these groups, although none of the moving individuals themselves tested positive for bTB. Significant increases in both the frequency of individual badger movements between groups and the emergence of bTB were observed in response to culling. However, no direct evidence was found to link the two phenomena. We hypothesise that the social disruption caused by culling may not only increase direct contact and thus disease transmission between surviving badgers, but may also increase social stress within the surviving population, causing immunosuppression and enhancing the expression of disease.",2011 Dec 14,"['Riordan, Philip', 'Delahay, Richard John', 'Cheeseman, Chris', 'Johnson, Paul James', 'Macdonald, David Whyte']",PLoS One,,,True
2b5319418280dbd7a7f5348c57c2a43b1fabc150,PMC,Adoption of an infection prevention and control programme (IPCP) in the Republic of Kiribati: a case study in diffusion of innovations theory,http://dx.doi.org/10.1186/1753-6561-5-S6-O20,PMC3239431,,CC BY,,2011 Jun 29,"['Zimmerman, P-A', 'Yeatman, H', 'Jones, M', 'Murdoch, H']",BMC Proc,,,False
740a8ab7bf183f64284384c5dfaae0ae77d56558,PMC,Synergistic Roles of Eukaryotic Translation Elongation Factors 1Bγ and 1A in Stimulation of Tombusvirus Minus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1002438,PMC3240602,22194687,CC BY,"Host factors are recruited into viral replicase complexes to aid replication of plus-strand RNA viruses. In this paper, we show that deletion of eukaryotic translation elongation factor 1Bgamma (eEF1Bγ) reduces Tomato bushy stunt virus (TBSV) replication in yeast host. Also, knock down of eEF1Bγ level in plant host decreases TBSV accumulation. eEF1Bγ binds to the viral RNA and is one of the resident host proteins in the tombusvirus replicase complex. Additional in vitro assays with whole cell extracts prepared from yeast strains lacking eEF1Bγ demonstrated its role in minus-strand synthesis by opening of the structured 3′ end of the viral RNA and reducing the possibility of re-utilization of (+)-strand templates for repeated (-)-strand synthesis within the replicase. We also show that eEF1Bγ plays a synergistic role with eukaryotic translation elongation factor 1A in tombusvirus replication, possibly via stimulation of the proper positioning of the viral RNA-dependent RNA polymerase over the promoter region in the viral RNA template.These roles for translation factors during TBSV replication are separate from their canonical roles in host and viral protein translation.",2011 Dec 15,"['Sasvari, Zsuzsanna', 'Izotova, Lara', 'Kinzy, Terri Goss', 'Nagy, Peter D.']",PLoS Pathog,,,True
d11eb07952f5a0fb076a49935508707abeecf8af,PMC,Clinical and Functional Characterization of URAT1 Variants,http://dx.doi.org/10.1371/journal.pone.0028641,PMC3241677,22194875,CC BY,"Idiopathic renal hypouricaemia is an inherited form of hypouricaemia, associated with abnormal renal handling of uric acid. There is excessive urinary wasting of uric acid resulting in hypouricaemia. Patients may be asymptomatic, but the persistent urinary abnormalities may manifest as renal stone disease, and hypouricaemia may manifest as exercise induced acute kidney injury. Here we have identified Macedonian and British patients with hypouricaemia, who presented with a variety of renal symptoms and signs including renal stone disease, hematuria, pyelonephritis and nephrocalcinosis. We have identified heterozygous missense mutations in SLC22A12 encoding the urate transporter protein URAT1 and correlate these genetic findings with functional characterization. Urate handling was determined using uptake experiments in HEK293 cells. This data highlights the importance of the URAT1 renal urate transporter in determining serum urate concentrations and the clinical phenotypes, including nephrolithiasis, that should prompt the clinician to suspect an inherited form of renal hypouricaemia.",2011 Dec 16,"['Tasic, Velibor', 'Hynes, Ann Marie', 'Kitamura, Kenichiro', 'Cheong, Hae Il', 'Lozanovski, Vladimir J.', 'Gucev, Zoran', 'Jutabha, Promsuk', 'Anzai, Naohiko', 'Sayer, John A.']",PLoS One,,,True
78f10dd6eb8860062bac9d5261b6881768bd7d7b,PMC,Internal versus external determinants of Schistosoma japonicum transmission in irrigated agricultural villages,http://dx.doi.org/10.1098/rsif.2011.0285,PMC3243390,21752808,CC BY,"Currently schistosomiasis transmission has been suppressed to low levels in many historically endemic areas of China by widespread use of praziquantel in human and bovine populations and application of niclosamide for snail control. However, re-emergent transmission has signalled the need for sustainable interventions beyond these repeated chemical interventions. To take advantage of ongoing investment in rural infrastructure, an index of schistosomiasis transmission potential is needed to identify villages where environmental modifications would be particularly effective. Based on a retrospective analysis of data from 10 villages in Sichuan Province, an index linked to the basic reproductive number is shown to have promise in meeting this need. However, a lack of methods for estimating the spatial components of the proposed metric and for estimating the import of cercariae and miracidia from neighbouring villages leads to significant uncertainty in its estimation. These findings suggest a priority effort to develop methods for measuring the free-swimming forms of the parasite in surface waters. This need is underscored by the high cost and limited sensitivity of current methods for diagnosing human infection and mounting evidence of the inadequacy of snail surveys to identify environments supporting low levels of transmission.",2012 Feb 7,"Spear, Robert C.",J R Soc Interface,,,True
ba03011c4b23d19642ea33554a6789895558ad97,PMC,Polyvalent DNA Vaccines Expressing HA Antigens of H5N1 Influenza Viruses with an Optimized Leader Sequence Elicit Cross-Protective Antibody Responses,http://dx.doi.org/10.1371/journal.pone.0028757,PMC3244406,22205966,CC BY,"Highly pathogenic avian influenza A (HPAI) H5N1 viruses are circulating among poultry populations in parts of Asia, Africa, and the Middle East, and have caused human infections with a high mortality rate. H5 subtype hemagglutinin (HA) has evolved into phylogenetically distinct clades and subclades based on viruses isolated from various avian species. Since 1997, humans have been infected by HPAI H5N1 viruses from several clades. It is, therefore, important to develop strategies to produce protective antibody responses against H5N1 viruses from multiple clades or antigenic groups. In the current study, we optimized the signal peptide design of DNA vaccines expressing HA antigens from H5N1 viruses. Cross reactivity analysis using sera from immunized rabbits showed that antibody responses elicited by a polyvalent formulation, including HA antigens from different clades, was able to elicit broad protective antibody responses against multiple key representative H5N1 viruses across different clades. Data presented in this report support the development of a polyvalent DNA vaccine strategy against the threat of a potential H5N1 influenza pandemic.",2011 Dec 21,"['Wang, Shixia', 'Hackett, Anthony', 'Jia, Na', 'Zhang, Chunhua', 'Zhang, Lu', 'Parker, Chris', 'Zhou, An', 'Li, Jun', 'Cao, Wu-Chun', 'Huang, Zuhu', 'Li, Yan', 'Lu, Shan']",PLoS One,,,True
716bf47d34e36f3c165ee3c84a70d93bf6f0bf5d,PMC,Epithelial Cells Derived from Swine Bone Marrow Express Stem Cell Markers and Support Influenza Virus Replication In Vitro,http://dx.doi.org/10.1371/journal.pone.0029567,PMC3245290,22216319,CC BY,"The bone marrow contains heterogeneous population of cells that are involved in the regeneration and repair of diseased organs, including the lungs. In this study, we isolated and characterized progenitor epithelial cells from the bone marrow of 4- to 5-week old germ-free pigs. Microscopically, the cultured cells showed epithelial-like morphology. Phenotypically, these cells expressed the stem cell markers octamer-binding transcription factor (Oct4) and stage-specific embryonic antigen-1 (SSEA-1), the alveolar stem cell marker Clara cell secretory protein (Ccsp), and the epithelial cell markers pan-cytokeratin (Pan-K), cytokeratin-18 (K-18), and occludin. When cultured in epithelial cell growth medium, the progenitor epithelial cells expressed type I and type II pneumocyte markers. Next, we examined the susceptibility of these cells to influenza virus. Progenitor epithelial cells expressed sialic acid receptors utilized by avian and mammalian influenza viruses and were targets for influenza virus replication. Additionally, differentiated type II but not type I pneumocytes supported the replication of influenza virus. Our data indicate that we have identified a unique population of progenitor epithelial cells in the bone marrow that might have airway reconstitution potential and may be a useful model for cell-based therapies for infectious and non-infectious lung diseases.",2011 Dec 22,"['Khatri, Mahesh', 'Saif, Yehia M.']",PLoS One,,,True
62426ec5038825e2c7928b6ac82a66ff1c2a578e,PMC,Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine,http://dx.doi.org/10.1371/journal.pcbi.1002315,PMC3245300,22215997,CC BY,"The H1N1 influenza pandemic of 2009 has claimed over 18,000 lives. During this pandemic, development of drug resistance further complicated efforts to control and treat the widespread illness. This research utilizes traditional Chinese medicine Database@Taiwan (TCM Database@Taiwan) to screen for compounds that simultaneously target H1 and N1 to overcome current difficulties with virus mutations. The top three candidates were de novo derivatives of xylopine and rosmaricine. Bioactivity of the de novo derivatives against N1 were validated by multiple machine learning prediction models. Ability of the de novo compounds to maintain CoMFA/CoMSIA contour and form key interactions implied bioactivity within H1 as well. Addition of a pyridinium fragment was critical to form stable interactions in H1 and N1 as supported by molecular dynamics (MD) simulation. Results from MD, hydrophobic interactions, and torsion angles are consistent and support the findings of docking. Multiple anchors and lack of binding to residues prone to mutation suggest that the TCM de novo derivatives may be resistant to drug resistance and are advantageous over conventional H1N1 treatments such as oseltamivir. These results suggest that the TCM de novo derivatives may be suitable candidates of dual-targeting drugs for influenza.",2011 Dec 22,"['Chang, Su-Sen', 'Huang, Hung-Jin', 'Chen, Calvin Yu-Chian']",PLoS Comput Biol,,,True
1f33cc82e136a1cc89b2382e6fcc6ae520e364ab,PMC,"Genetic diversity of group A rotaviruses associated with repeated outbreaks of diarrhea in a farrow-to-finish farm: identification of a porcine rotavirus strain bearing a novel VP7 genotype, G26",http://dx.doi.org/10.1186/1297-9716-42-112,PMC3245447,22067072,CC BY,"Group A rotaviruses (GARs) are one of the most common causes of diarrhea in suckling pigs. Although a number of G and P genotypes have been identified in porcine GARs, few attempts have been made to study the molecular epidemiology of these viruses associated with diarrhea outbreaks within a farm over an extended period of time. Here, we investigated the molecular characteristics of GARs that caused four outbreaks of diarrhea among suckling pigs in a farrow-to-finish farm over the course of a year. G and P genotyping of GARs detected at each outbreak demonstrated genetic diversity in this farm as follows: G9P[23] was detected at the first outbreak, G9P[13]/[22] and G9P[23] at the second, G3P[7] at the third, and G9P[23], G5P[13]/[22], and P[7] combined with an untypeable G genotype at the fourth. Sequence analysis of the detected GARs revealed that such genetic diversity could have resulted not only from the introduction of new GAR strains, but also from gene reassortment between GAR strains within the farm. Further, the GAR strain carrying the untypeable G genotype was shown to be a novel porcine GAR bearing a new G26 genotype, as confirmed by the Rotavirus Classification Working Group.",2011 Nov 9,"['Miyazaki, Ayako', 'Kuga, Kazufumi', 'Suzuki, Tohru', 'Kohmoto, Mariko', 'Katsuda, Ken', 'Tsunemitsu, Hiroshi']",Vet Res,,,True
026c59766e222f22b416a6525ae3194a140b5faa,PMC,Two Novel Parvoviruses in Frugivorous New and Old World Bats,http://dx.doi.org/10.1371/journal.pone.0029140,PMC3246463,22216187,CC BY,"Bats, a globally distributed group of mammals with high ecological importance, are increasingly recognized as natural reservoir hosts for viral agents of significance to human and animal health. In the present study, we evaluated pools of blood samples obtained from two phylogenetically distant bat families, in particular from flying foxes (Pteropodidae), Eidolon helvum in West Africa, and from two species of New World leaf-nosed fruit bats (Phyllostomidae), Artibeus jamaicensis and Artibeus lituratus in Central America. A sequence-independent virus discovery technique (VIDISCA) was used in combination with high throughput sequencing to detect two novel parvoviruses: a PARV4-like virus named Eh-BtPV-1 in Eidolon helvum from Ghana and the first member of a putative new genus in Artibeus jamaicensis from Panama (Aj-BtPV-1). Those viruses were circulating in the corresponding bat colony at rates of 7–8%. Aj-BtPV-1 was also found in Artibeus lituratus (5.5%). Both viruses were detected in the blood of infected animals at high concentrations: up to 10E8 and to 10E10 copies/ml for Aj-BtPV-1 and Eh-BtPV-1 respectively. Eh-BtPV-1 was additionally detected in all organs collected from bats (brain, lungs, liver, spleen, kidneys and intestine) and spleen and kidneys were identified as the most likely sites where viral replication takes place. Our study shows that bat parvoviruses share common ancestors with known parvoviruses of humans and livestock. We also provide evidence that a variety of Parvovirinae are able to cause active infection in bats and that they are widely distributed in these animals with different geographic origin, ecologies and climatic ranges.",2011 Dec 27,"['Canuti, Marta', 'Eis-Huebinger, Anna Maria', 'Deijs, Martin', 'de Vries, Michel', 'Drexler, Jan Felix', 'Oppong, Samuel K.', 'Müller, Marcel A.', 'Klose, Stefan M.', 'Wellinghausen, Nele', 'Cottontail, Veronika M.', 'Kalko, Elisabeth K. V.', 'Drosten, Christian', 'van der Hoek, Lia']",PLoS One,,,True
550494d6d01569a05a8ca2d75f892486b01d1865,PMC,Diseases and Causes of Death in European Bats: Dynamics in Disease Susceptibility and Infection Rates,http://dx.doi.org/10.1371/journal.pone.0029773,PMC3247292,22216354,CC BY,"BACKGROUND: Bats receive increasing attention in infectious disease studies, because of their well recognized status as reservoir species for various infectious agents. This is even more important, as bats with their capability of long distance dispersal and complex social structures are unique in the way microbes could be spread by these mammalian species. Nevertheless, infection studies in bats are predominantly limited to the identification of specific pathogens presenting a potential health threat to humans. But the impact of infectious agents on the individual host and their importance on bat mortality is largely unknown and has been neglected in most studies published to date. METHODOLOGY/PRINCIPAL FINDINGS: Between 2002 and 2009, 486 deceased bats of 19 European species (family Vespertilionidae) were collected in different geographic regions in Germany. Most animals represented individual cases that have been incidentally found close to roosting sites or near human habitation in urban and urban-like environments. The bat carcasses were subjected to a post-mortem examination and investigated histo-pathologically, bacteriologically and virologically. Trauma and disease represented the most important causes of death in these bats. Comparative analysis of pathological findings and microbiological results show that microbial agents indeed have an impact on bats succumbing to infectious diseases, with fatal bacterial, viral and parasitic infections found in at least 12% of the bats investigated. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the importance of diseases and infectious agents as cause of death in European bat species. The clear seasonal and individual variations in disease prevalence and infection rates indicate that maternity colonies are more susceptible to infectious agents, underlining the possible important role of host physiology, immunity and roosting behavior as risk factors for infection of bats.",2011 Dec 28,"['Mühldorfer, Kristin', 'Speck, Stephanie', 'Kurth, Andreas', 'Lesnik, René', 'Freuling, Conrad', 'Müller, Thomas', 'Kramer-Schadt, Stephanie', 'Wibbelt, Gudrun']",PLoS One,,,True
aefd921eef67855fd84f460502e9e7277aeb92a1,PMC,Collaboration between infection control and occupational health in three continents: a success story with international impact,http://dx.doi.org/10.1186/1472-698X-11-S2-S8,PMC3247839,22166059,CC BY,"Globalization has been accompanied by the rapid spread of infectious diseases, and further strain on working conditions for health workers globally. Post-SARS, Canadian occupational health and infection control researchers got together to study how to better protect health workers, and found that training was indeed perceived as key to a positive safety culture. This led to developing information and communication technology (ICT) tools. The research conducted also showed the need for better workplace inspections, so a workplace audit tool was also developed to supplement worker questionnaires and the ICT. When invited to join Ecuadorean colleagues to promote occupational health and infection control, these tools were collectively adapted and improved, including face-to-face as well as on-line problem-based learning scenarios. The South African government then invited the team to work with local colleagues to improve occupational health and infection control, resulting in an improved web-based health information system to track incidents, exposures, and occupational injury and diseases. As the H1N1 pandemic struck, the online infection control course was adapted and translated into Spanish, as was a novel skill-building learning tool that permits health workers to practice selecting personal protective equipment. This tool was originally developed in collaboration with the countries from the Caribbean region and the Pan American Health Organization (PAHO). Research from these experiences led to strengthened focus on building capacity of health and safety committees, and new modules are thus being created, informed by that work. The products developed have been widely heralded as innovative and interactive, leading to their inclusion into “toolkits” used internationally. The tools used in Canada were substantially improved from the collaborative adaptation process for South and Central America and South Africa. This international collaboration between occupational health and infection control researchers led to the improvement of the research framework and development of tools, guidelines and information systems. Furthermore, the research and knowledge-transfer experience highlighted the value of partnership amongst Northern and Southern researchers in terms of sharing resources, experiences and knowledge.",2011 Nov 8,"['Yassi, Annalee', 'Bryce, Elizabeth A', 'Breilh, Jaime', 'Lavoie, Marie-Claude', 'Ndelu, Lindiwe', 'Lockhart, Karen', 'Spiegel, Jerry']",BMC Int Health Hum Rights,,,True
e344d21fb68d14bed65d7fbdc97164e61717a0f2,PMC,Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions,http://dx.doi.org/10.1371/journal.pone.0029491,PMC3248422,22220213,CC BY,"Given a compound, how can we effectively predict its biological function? It is a fundamentally important problem because the information thus obtained may benefit the understanding of many basic biological processes and provide useful clues for drug design. In this study, based on the information of chemical-chemical interactions, a novel method was developed that can be used to identify which of the following eleven metabolic pathway classes a query compound may be involved with: (1) Carbohydrate Metabolism, (2) Energy Metabolism, (3) Lipid Metabolism, (4) Nucleotide Metabolism, (5) Amino Acid Metabolism, (6) Metabolism of Other Amino Acids, (7) Glycan Biosynthesis and Metabolism, (8) Metabolism of Cofactors and Vitamins, (9) Metabolism of Terpenoids and Polyketides, (10) Biosynthesis of Other Secondary Metabolites, (11) Xenobiotics Biodegradation and Metabolism. It was observed that the overall success rate obtained by the method via the 5-fold cross-validation test on a benchmark dataset consisting of 3,137 compounds was 77.97%, which is much higher than 10.45%, the corresponding success rate obtained by the random guesses. Besides, to deal with the situation that some compounds may be involved with more than one metabolic pathway class, the method presented here is featured by the capacity able to provide a series of potential metabolic pathway classes ranked according to the descending order of their likelihood for each of the query compounds concerned. Furthermore, our method was also applied to predict 5,549 compounds whose metabolic pathway classes are unknown. Interestingly, the results thus obtained are quite consistent with the deductions from the reports by other investigators. It is anticipated that, with the continuous increase of the chemical-chemical interaction data, the current method will be further enhanced in its power and accuracy, so as to become a useful complementary vehicle in annotating uncharacterized compounds for their biological functions.",2011 Dec 29,"['Hu, Le-Le', 'Chen, Chen', 'Huang, Tao', 'Cai, Yu-Dong', 'Chou, Kuo-Chen']",PLoS One,,,True
5b6ffa9ab26b453363555a8ab5943464a9f0c5e5,PMC,Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions,http://dx.doi.org/10.1371/journal.pone.0029491,PMC3248422,22220213,CC BY,"Given a compound, how can we effectively predict its biological function? It is a fundamentally important problem because the information thus obtained may benefit the understanding of many basic biological processes and provide useful clues for drug design. In this study, based on the information of chemical-chemical interactions, a novel method was developed that can be used to identify which of the following eleven metabolic pathway classes a query compound may be involved with: (1) Carbohydrate Metabolism, (2) Energy Metabolism, (3) Lipid Metabolism, (4) Nucleotide Metabolism, (5) Amino Acid Metabolism, (6) Metabolism of Other Amino Acids, (7) Glycan Biosynthesis and Metabolism, (8) Metabolism of Cofactors and Vitamins, (9) Metabolism of Terpenoids and Polyketides, (10) Biosynthesis of Other Secondary Metabolites, (11) Xenobiotics Biodegradation and Metabolism. It was observed that the overall success rate obtained by the method via the 5-fold cross-validation test on a benchmark dataset consisting of 3,137 compounds was 77.97%, which is much higher than 10.45%, the corresponding success rate obtained by the random guesses. Besides, to deal with the situation that some compounds may be involved with more than one metabolic pathway class, the method presented here is featured by the capacity able to provide a series of potential metabolic pathway classes ranked according to the descending order of their likelihood for each of the query compounds concerned. Furthermore, our method was also applied to predict 5,549 compounds whose metabolic pathway classes are unknown. Interestingly, the results thus obtained are quite consistent with the deductions from the reports by other investigators. It is anticipated that, with the continuous increase of the chemical-chemical interaction data, the current method will be further enhanced in its power and accuracy, so as to become a useful complementary vehicle in annotating uncharacterized compounds for their biological functions.",2011 Dec 29,"['Hu, Le-Le', 'Chen, Chen', 'Huang, Tao', 'Cai, Yu-Dong', 'Chou, Kuo-Chen']",PLoS One,,,False
fc9a6a00498ee4dfeaf7c201c3341aca6ad21409,PMC,Identification and Characterization of a Novel Non-Structural Protein of Bluetongue Virus,http://dx.doi.org/10.1371/journal.ppat.1002477,PMC3248566,22241985,CC BY,"Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell.",2011 Dec 29,"['Ratinier, Maxime', 'Caporale, Marco', 'Golder, Matthew', 'Franzoni, Giulia', 'Allan, Kathryn', 'Nunes, Sandro Filipe', 'Armezzani, Alessia', 'Bayoumy, Amr', 'Rixon, Frazer', 'Shaw, Andrew', 'Palmarini, Massimo']",PLoS Pathog,,,True
ea77ef3c24536b33485875684a34ca6539084c5c,PMC,Acute Respiratory Distress Syndrome Induced by a Swine 2009 H1N1 Variant in Mice,http://dx.doi.org/10.1371/journal.pone.0029347,PMC3250439,22235288,CC BY,"BACKGROUND: Acute respiratory distress syndrome (ARDS) induced by pandemic 2009 H1N1 influenza virus has been widely reported and was considered the main cause of death in critically ill patients with 2009 H1N1 infection. However, no animal model has been developed for ARDS caused by infection with 2009 H1N1 virus. Here, we present a mouse model of ARDS induced by 2009 H1N1 virus. METHODOLOGY PRINCIPAL FINDINGS: Mice were inoculated with A/swine/Shandong/731/2009 (SD/09), which was a 2009 H1N1 influenza variant with a G222D mutation in the hemagglutinin. Clinical symptoms were recorded every day. Lung injury was assessed by lung water content and histopathological observation. Arterial blood gas, leukocyte count in the bronchial alveolar lavage fluid and blood, virus titers, and cytokine levels in the lung were measured at various times post-inoculation. Mice infected with SD/09 virus showed typical ARDS symptoms characterized by 60% lethality on days 8–10 post-inoculation, highly edematous lungs, inflammatory cellular infiltration, alveolar and interstitial edema, lung hemorrhage, progressive and severe hypoxemia, and elevated levels of proinflammatory cytokines and chemokines. CONCLUSIONS/SIGNIFICANCE: These results suggested that we successfully established an ARDS mouse model induced by a virulent 2009 H1N1 variant without previous adaptation, which may be of benefit for evaluating the pathogenesis or therapy of human ARDS caused by 2009 H1N1 virus.",2012 Jan 3,"['Zhang, Yi', 'Sun, Honglei', 'Fan, Lihong', 'Ma, Yuan', 'Sun, Yipeng', 'Pu, Juan', 'Yang, Jun', 'Qiao, Jian', 'Ma, Guangpeng', 'Liu, Jinhua']",PLoS One,,,True
315303952d93ba93f55029cca73e2f483bc16362,PMC,True versus False Parasite Interactions: A Robust Method to Take Risk Factors into Account and Its Application to Feline Viruses,http://dx.doi.org/10.1371/journal.pone.0029618,PMC3250451,22235312,CC BY,"BACKGROUND: Multiple infections are common in natural host populations and interspecific parasite interactions are therefore likely within a host individual. As they may seriously impact the circulation of certain parasites and the emergence and management of infectious diseases, their study is essential. In the field, detecting parasite interactions is rendered difficult by the fact that a large number of co-infected individuals may also be observed when two parasites share common risk factors. To correct for these “false interactions”, methods accounting for parasite risk factors must be used. METHODOLOGY/PRINCIPAL FINDINGS: In the present paper we propose such a method for presence-absence data (i.e., serology). Our method enables the calculation of the expected frequencies of single and double infected individuals under the independence hypothesis, before comparing them to the observed ones using the chi-square statistic. The method is termed “the corrected chi-square.” Its robustness was compared to a pre-existing method based on logistic regression and the corrected chi-square proved to be much more robust for small sample sizes. Since the logistic regression approach is easier to implement, we propose as a rule of thumb to use the latter when the ratio between the sample size and the number of parameters is above ten. Applied to serological data for four viruses infecting cats, the approach revealed pairwise interactions between the Feline Herpesvirus, Parvovirus and Calicivirus, whereas the infection by FIV, the feline equivalent of HIV, did not modify the risk of infection by any of these viruses. CONCLUSIONS/SIGNIFICANCE: This work therefore points out possible interactions that can be further investigated in experimental conditions and, by providing a user-friendly R program and a tutorial example, offers new opportunities for animal and human epidemiologists to detect interactions of interest in the field, a crucial step in the challenge of multiple infections.",2012 Jan 3,"['Hellard, Eléonore', 'Pontier, Dominique', 'Sauvage, Frank', 'Poulet, Hervé', 'Fouchet, David']",PLoS One,,,True
2239f23b3b6738f24cd381b0ee59faaf39a8a027,PMC,The Transmembrane Domain of CEACAM1-4S Is a Determinant of Anchorage Independent Growth and Tumorigenicity,http://dx.doi.org/10.1371/journal.pone.0029606,PMC3250453,22235309,CC BY,"CEACAM1 is a multifunctional Ig-like cell adhesion molecule expressed by epithelial cells in many organs. CEACAM1-4L and CEACAM1-4S, two isoforms produced by differential splicing, are predominant in rat liver. Previous work has shown that downregulation of both isoforms occurs in rat hepatocellular carcinomas. Here, we have isolated an anchorage dependent clone, designated 253T-NT that does not express detectable levels of CEACAM1. Stable transfection of 253-NT cells with a wild type CEACAM1-4S expression vector induced an anchorage independent growth in vitro and a tumorigenic phenotype in vivo. These phenotypes were used as quantifiable end points to examine the functionality of the CEACAM1-4S transmembrane domain. Examination of the CEACAM1 transmembrane domain showed N-terminal GXXXG dimerization sequences and C-terminal tyrosine residues shown in related studies to stabilize transmembrane domain helix-helix interactions. To examine the effects of transmembrane domain mutations, 253-NT cells were transfected with transmembrane domain mutants carrying glycine to leucine or tyrosine to valine substitutions. Results showed that mutation of transmembrane tyrosine residues greatly enhanced growth in vitro and in vivo. Mutation of transmembrane dimerization motifs, in contrast, significantly reduced anchorage independent growth and tumorigenicity. 253-NT cells expressing CEACAM1-4S with both glycine to leucine and tyrosine to valine mutations displayed the growth-enhanced phenotype of tyrosine mutants. The dramatic effect of transmembrane domain mutations constitutes strong evidence that the transmembrane domain is an important determinant of CEACAM1-4S functionality and most likely by other proteins with transmembrane domains containing dimerization sequences and/or C-terminal tyrosine residues.",2012 Jan 3,"['Lawson, Erica L.', 'Mills, David R.', 'Brilliant, Kate E.', 'Hixson, Douglas C.']",PLoS One,,,True
cdf3bcf39150a5ef5537651e90d93cbccd097f79,PMC,"Etiology and Clinical Characteristics of Influenza-Like Illness (ILI) in Outpatients in Beijing, June 2010 to May 2011",http://dx.doi.org/10.1371/journal.pone.0028786,PMC3251557,22238581,CC BY,"BACKGROUND: Since May 2009, exposure of the population of Beijing, China to pH1N1 has resulted in an increase in respiratory illnesses. Limited information is available on the etiology and clinical characteristics of the influenza-like illness (ILI) that ensued in adults following the pH1N1 pandemic. METHODS: Clinical and epidemiological data of ILI in adults was collected. A total of 279 throat swabs were tested for twelve respiratory viruses using multiplex RT-PCR. Clinical characteristics of influenza A in outpatients versus test-negative patients were compared using Pearson's χ2 and the Mann-Whitney U test. 190 swabs were tested for pH1N1 by virus isolation. Consultation rates for ILI were compared between 2009 and 2010. RESULTS: One or two virus were detected in 29% of the samples. Influenza A virus (FLU-A) accounted for 22.9% (64/279). Other viruses were present at a frequency less than 3.0%. Cough was significantly associated with Influenza A virus infection (χ2, p<0.001). The positive rate of FLU-A was consistent with changes in the ILI rate during the same period and there was a significant reduction in the incidence of ILI in 2010 when compared to 2009. During the 2010–2011 influenza season, the incidence peaked in January 2011 in Beijing and north China. CONCLUSIONS: Exposure to pH1N1 had no impact on typical influenza seasonal peaks, although FLU-A remained the predominant virus for 2010 in Beijing. Symptomatically, cough was associated with FLU-A infection. The positive rate of influenza virus was consistent with changes in the ILI rate during the same period and there was a significant reduction in the incidence of ILI in 2010 when compared to that of 2009.",2012 Jan 4,"['Yang, XiaoHua', 'Yao, Yao', 'Chen, MeiFang', 'Yang, Xia', 'Xie, YanDi', 'Liu, YaFen', 'Zhao, XiuYing', 'Gao, Yan', 'Wei, Lai']",PLoS One,,,True
a447f42b4f4ed16afea798513f8c1409ee2252fa,PMC,Human Subtilase SKI-1/S1P Is a Master Regulator of the HCV Lifecycle and a Potential Host Cell Target for Developing Indirect-Acting Antiviral Agents,http://dx.doi.org/10.1371/journal.ppat.1002468,PMC3252376,22241994,CC BY,"HCV infection is a major risk factor for liver cancer and liver transplantation worldwide. Overstimulation of host lipid metabolism in the liver by HCV-encoded proteins during viral infection creates a favorable environment for virus propagation and pathogenesis. In this study, we hypothesize that targeting cellular enzymes acting as master regulators of lipid homeostasis could represent a powerful approach to developing a novel class of broad-spectrum antivirals against infection associated with human Flaviviridae viruses such as hepatitis C virus (HCV), whose assembly and pathogenesis depend on interaction with lipid droplets (LDs). One such master regulator of cholesterol metabolic pathways is the host subtilisin/kexin-isozyme-1 (SKI-1) – or site-1 protease (S1P). SKI-1/S1P plays a critical role in the proteolytic activation of sterol regulatory element binding proteins (SREBPs), which control expression of the key enzymes of cholesterol and fatty-acid biosynthesis. Here we report the development of a SKI-1/S1P-specific protein-based inhibitor and its application to blocking the SREBP signaling cascade. We demonstrate that SKI-1/S1P inhibition effectively blocks HCV from establishing infection in hepatoma cells. The inhibitory mechanism is associated with a dramatic reduction in the abundance of neutral lipids, LDs, and the LD marker: adipose differentiation-related protein (ADRP)/perilipin 2. Reduction of LD formation inhibits virus assembly from infected cells. Importantly, we confirm that SKI-1/S1P is a key host factor for HCV infection by using a specific active, site-directed, small-molecule inhibitor of SKI-1/S1P: PF-429242. Our studies identify SKI-1/S1P as both a novel regulator of the HCV lifecycle and as a potential host-directed therapeutic target against HCV infection and liver steatosis. With identification of an increasing number of human viruses that use host LDs for infection, our results suggest that SKI-1/S1P inhibitors may allow development of novel broad-spectrum biopharmaceuticals that could lead to novel indirect-acting antiviral options with the current standard of care.",2012 Jan 5,"['Olmstead, Andrea D.', 'Knecht, Wolfgang', 'Lazarov, Ina', 'Dixit, Surjit B.', 'Jean, François']",PLoS Pathog,,,True
667001630cb051990f577e069785590fce4b4d14,PMC,"Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.",http://dx.doi.org/10.3762/bjoc.7.192,PMC3252867,22238541,CC BY,"The marine-derived fungus Stachylidium sp. was isolated from the sponge Callyspongia sp. cf. C. flammea. Culture on a biomalt medium supplemented with sea salt led to the isolation of three new phthalide derivatives, i.e., marilones A–C (1–3), and the known compound silvaticol (4). The skeleton of marilones A and B is most unusual, and its biosynthesis is suggested to require unique biochemical reactions considering fungal secondary metabolism. Marilone A (1) was found to have antiplasmodial activity against Plasmodium berghei liver stages with an IC(50) of 12.1 µM. Marilone B (2) showed selective antagonistic activity towards the serotonin receptor 5-HT(2B) with a K (i) value of 7.7 µM.",2011 Dec 5,"['Almeida, Celso', 'Kehraus, Stefan', 'Prudêncio, Miguel', 'König, Gabriele M']",Beilstein J Org Chem,,,True
ed50424d38934442bddddf2ce928c4b4d5c2c7d4,PMC,"Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.",http://dx.doi.org/10.3762/bjoc.7.192,PMC3252867,22238541,CC BY,"The marine-derived fungus Stachylidium sp. was isolated from the sponge Callyspongia sp. cf. C. flammea. Culture on a biomalt medium supplemented with sea salt led to the isolation of three new phthalide derivatives, i.e., marilones A–C (1–3), and the known compound silvaticol (4). The skeleton of marilones A and B is most unusual, and its biosynthesis is suggested to require unique biochemical reactions considering fungal secondary metabolism. Marilone A (1) was found to have antiplasmodial activity against Plasmodium berghei liver stages with an IC(50) of 12.1 µM. Marilone B (2) showed selective antagonistic activity towards the serotonin receptor 5-HT(2B) with a K (i) value of 7.7 µM.",2011 Dec 5,"['Almeida, Celso', 'Kehraus, Stefan', 'Prudêncio, Miguel', 'König, Gabriele M']",Beilstein J Org Chem,,,False
5eccf590cffbe86092abe652fa471515e9f37249,PMC,Contact with Domestic Dogs Increases Pathogen Exposure in Endangered African Wild Dogs (Lycaon pictus),http://dx.doi.org/10.1371/journal.pone.0030099,PMC3253127,22238695,CC BY,"BACKGROUND: Infectious diseases have contributed to the decline and local extinction of several wildlife species, including African wild dogs (Lycaon pictus). Mitigating such disease threats is challenging, partly because uncertainty about disease dynamics makes it difficult to identify the best management approaches. Serious impacts on susceptible populations most frequently occur when generalist pathogens are maintained within populations of abundant (often domestic) “reservoir” hosts, and spill over into less abundant host species. If this is the case, disease control directed at the reservoir host might be most appropriate. However, pathogen transmission within threatened host populations may also be important, and may not be controllable by managing another host species. METHODOLOGY/PRINCIPAL FINDINGS: We investigated interspecific and intraspecific transmission routes, by comparing African wild dogs' exposure to six canine pathogens with behavioural measures of their opportunities for contact with domestic dogs and with other wild dogs. Domestic dog contact was associated with exposure to canine parvovirus, Ehrlichia canis, Neospora caninum and perhaps rabies virus, but not with exposure to canine distemper virus or canine coronavirus. Contact with other wild dogs appeared not to increase the risk of exposure to any of the pathogens. CONCLUSIONS/SIGNIFICANCE: These findings, combined with other data, suggest that management directed at domestic dogs might help to protect wild dog populations from rabies virus, but not from canine distemper virus. However, further analyses are needed to determine the management approaches – including no intervention – which are most appropriate for each pathogen.",2012 Jan 6,"['Woodroffe, Rosie', 'Prager, Katherine C.', 'Munson, Linda', 'Conrad, Patricia A.', 'Dubovi, Edward J.', 'Mazet, Jonna A. K.']",PLoS One,,,True
1ba33d95f798c3f591766786b165215875278bc7,PMC,Zoonotic Viruses Associated with Illegally Imported Wildlife Products,http://dx.doi.org/10.1371/journal.pone.0029505,PMC3254615,22253731,CC0,"The global trade in wildlife has historically contributed to the emergence and spread of infectious diseases. The United States is the world's largest importer of wildlife and wildlife products, yet minimal pathogen surveillance has precluded assessment of the health risks posed by this practice. This report details the findings of a pilot project to establish surveillance methodology for zoonotic agents in confiscated wildlife products. Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP) and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. Pathogen screening identified retroviruses (simian foamy virus) and/or herpesviruses (cytomegalovirus and lymphocryptovirus) in the NHP samples. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence.",2012 Jan 10,"['Smith, Kristine M.', 'Anthony, Simon J.', 'Switzer, William M.', 'Epstein, Jonathan H.', 'Seimon, Tracie', 'Jia, Hongwei', 'Sanchez, Maria D.', 'Huynh, Thanh Thao', 'Galland, G. Gale', 'Shapiro, Sheryl E.', 'Sleeman, Jonathan M.', 'McAloose, Denise', 'Stuchin, Margot', 'Amato, George', 'Kolokotronis, Sergios-Orestis', 'Lipkin, W. Ian', 'Karesh, William B.', 'Daszak, Peter', 'Marano, Nina']",PLoS One,,,True
5eeeb39d1eda252e3ba5fff3596679b8e3376f8d,PMC,"Alzheimer's Disease: APP, Gamma Secretase, APOE, CLU, CR1, PICALM, ABCA7, BIN1, CD2AP, CD33, EPHA1, and MS4A2, and Their Relationships with Herpes Simplex, C. Pneumoniae, Other Suspect Pathogens, and the Immune System",http://dx.doi.org/10.4061/2011/501862,PMC3255168,22254144,CC BY,"Alzheimer's disease susceptibility genes, APP and gamma-secretase, are involved in the herpes simplex life cycle, and that of other suspect pathogens (C. pneumoniae, H. pylori, C. neoformans, B. burgdorferri, P. gingivalis) or immune defence. Such pathogens promote beta-amyloid deposition and tau phosphorylation and may thus be causative agents, whose effects are conditioned by genes. The antimicrobial effects of beta-amyloid, the localisation of APP/gamma-secretase in immunocompetent dendritic cells, and gamma secretase cleavage of numerous pathogen receptors suggest that this network is concerned with pathogen disposal, effects which may be abrogated by the presence of beta-amyloid autoantibodies in the elderly. These autoantibodies, as well as those to nerve growth factor and tau, also observed in Alzheimer's disease, may well be antibodies to pathogens, due to homology between human autoantigens and pathogen proteins. NGF or tau antibodies promote beta-amyloid deposition, neurofibrillary tangles, or cholinergic neuronal loss, and, with other autoantibodies, such as anti-ATPase, are potential agents of destruction, whose formation is dictated by sequence homology between pathogen and human proteins, and thus by pathogen strain and human genes. Pathogen elimination in the ageing population and removal of culpable autoantibodies might reduce the incidence and offer hope for a cure in this affliction.",2011 Dec 29,"Carter, Chris",Int J Alzheimers Dis,,,True
9104d87ad3991408937aa1e1739e7df0f51d01b0,PMC,"The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy",http://dx.doi.org/10.1371/journal.pone.0029608,PMC3256159,22247782,CC BY,"BACKGROUND: Filoviruses, including Ebola virus, are unusual in being filamentous animal viruses. Structural data on the arrangement, stoichiometry and organisation of the component molecules of filoviruses has until now been lacking, partially due to the need to work under level 4 biological containment. The present study provides unique insights into the structure of this deadly pathogen. METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. We show that the helical Ebola virus inner nucleocapsid containing RNA and nucleoprotein is stabilized by an outer layer of VP24-VP35 bridges. Elucidation of the structure of the membrane-associated glycoprotein in its native state indicates that the putative receptor-binding site is occluded within the molecule, while a major neutralizing epitope is exposed on its surface proximal to the viral envelope. The matrix protein VP40 forms a regular lattice within the envelope, although its contacts with the nucleocapsid are irregular. CONCLUSIONS: The results of this study demonstrate a modular organization in Ebola virus that accommodates a well-ordered, symmetrical nucleocapsid within a flexible, tubular membrane envelope.",2012 Jan 11,"['Beniac, Daniel R.', 'Melito, Pasquale L.', 'deVarennes, Shauna L.', 'Hiebert, Shannon L.', 'Rabb, Melissa J.', 'Lamboo, Lindsey L.', 'Jones, Steven M.', 'Booth, Timothy F.']",PLoS One,,,True
693d0f533004851d03a1f38a336f6aa943ea2733,PMC,"Up-Regulation of Mcl-1 and Bak by Coronavirus Infection of Human, Avian and Animal Cells Modulates Apoptosis and Viral Replication",http://dx.doi.org/10.1371/journal.pone.0030191,PMC3256233,22253918,CC BY,"Virus-induced apoptosis and viral mechanisms that regulate this cell death program are key issues in understanding virus-host interactions and viral pathogenesis. Like many other human and animal viruses, coronavirus infection of mammalian cells induces apoptosis. In this study, the global gene expression profiles are first determined in IBV-infected Vero cells at 24 hours post-infection by Affymetrix array, using avian coronavirus infectious bronchitis virus (IBV) as a model system. It reveals an up-regulation at the transcriptional level of both pro-apoptotic Bak and pro-survival myeloid cell leukemia-1 (Mcl-1). These results were further confirmed both in vivo and in vitro, in IBV-infected embryonated chicken eggs, chicken fibroblast cells and mammalian cells at transcriptional and translational levels, respectively. Interestingly, the onset of apoptosis occurred earlier in IBV-infected mammalian cells silenced with short interfering RNA targeting Mcl-1 (siMcl-1), and was delayed in cells silenced with siBak. IBV progeny production and release were increased in infected Mcl-1 knockdown cells compared to similarly infected control cells, while the contrary was observed in infected Bak knockdown cells. Furthermore, IBV infection-induced up-regulation of GADD153 regulated the expression of Mcl-1. Inhibition of the mitogen-activated protein/extracellular signal-regulated kinase (MEK/ERK) and phosphoinositide 3-kinase (PI3K/Akt) signaling pathways by chemical inhibitors and knockdown of GADD153 by siRNA demonstrated the involvement of ER-stress response in regulation of IBV-induced Mcl-1 expression. These results illustrate the sophisticated regulatory strategies evolved by a coronavirus to modulate both virus-induced apoptosis and viral replication during its replication cycle.",2012 Jan 11,"['Zhong, Yanxin', 'Liao, Ying', 'Fang, Shouguo', 'Tam, James P.', 'Liu, Ding Xiang']",PLoS One,,,True
4e45a8379e00a6551b99dcb0c8ba91b7b358f853,PMC,"3D QSAR Pharmacophore Modeling, in Silico Screening, and Density Functional Theory (DFT) Approaches for Identification of Human Chymase Inhibitors",http://dx.doi.org/10.3390/ijms12129236,PMC3257128,22272131,CC BY,"Human chymase is a very important target for the treatment of cardiovascular diseases. Using a series of theoretical methods like pharmacophore modeling, database screening, molecular docking and Density Functional Theory (DFT) calculations, an investigation for identification of novel chymase inhibitors, and to specify the key factors crucial for the binding and interaction between chymase and inhibitors is performed. A highly correlating (r = 0.942) pharmacophore model (Hypo1) with two hydrogen bond acceptors, and three hydrophobic aromatic features is generated. After successfully validating “Hypo1”, it is further applied in database screening. Hit compounds are subjected to various drug-like filtrations and molecular docking studies. Finally, three structurally diverse compounds with high GOLD fitness scores and interactions with key active site amino acids are identified as potent chymase hits. Moreover, DFT study is performed which confirms very clear trends between electronic properties and inhibitory activity (IC(50)) data thus successfully validating “Hypo1” by DFT method. Therefore, this research exertion can be helpful in the development of new potent hits for chymase. In addition, the combinational use of docking, orbital energies and molecular electrostatic potential analysis is also demonstrated as a good endeavor to gain an insight into the interaction between chymase and inhibitors.",2011 Dec 12,"['Arooj, Mahreen', 'Thangapandian, Sundarapandian', 'John, Shalini', 'Hwang, Swan', 'Park, Jong Keun', 'Lee, Keun Woo']",Int J Mol Sci,,,True
1a5c7512b0e842a7b5f1d1511d0f035a0dbc3c25,PMC,SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b,http://dx.doi.org/10.1371/journal.pone.0029542,PMC3257236,22253733,CC BY,"BACKGROUND: The causative agent of severe acute respiratory syndrome, SARS coronavirus (SARS-CoV) genome encodes several unique group specific accessory proteins with unknown functions. Among them, accessory protein 3b (also known as ORF4) was lately identified as one of the viral interferon antagonist. Recently our lab uncovered a new role for 3b in upregulation of AP-1 transcriptional activity and its downstream genes. Thus, we believe that 3b might play an important role in SARS-CoV pathogenesis and therefore is of considerable interest. The current study aims at identifying novel host cellular interactors of the 3b protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using yeast two-hybrid and co-immunoprecipitation techniques, we have identified a host transcription factor RUNX1b (Runt related transcription factor, isoform b) as a novel interacting partner for SARS-CoV 3b protein. Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. Kinase assay and pharmacological inhibitor treatment implied that 3b also affect RUNX1b transcriptional activity by regulating its ERK dependent phosphorylation levels. Additionally, mRNA levels of MIP-1α, a RUNX1b target gene upregulated in SARS-CoV infected monocyte-derived dendritic cells, were found to be elevated in 3b expressing U937 monocyte cells. CONCLUSIONS/SIGNIFICANCE: These results unveil a novel interaction of SARS-CoV 3b with the host factor, RUNX1b, and speculate its physiological relevance in upregulating cytokines and chemokine levels in state of SARS virus infection.",2012 Jan 12,"['Varshney, Bhavna', 'Agnihotram, Sudhakar', 'Tan, Yee-Joo', 'Baric, Ralph', 'Lal, Sunil K.']",PLoS One,,,True
5566d234b7245b606a50f808fe09b5e3a4f04711,PMC,Henipavirus Neutralising Antibodies in an Isolated Island Population of African Fruit Bats,http://dx.doi.org/10.1371/journal.pone.0030346,PMC3257271,22253928,CC0,"Isolated islands provide valuable opportunities to study the persistence of viruses in wildlife populations, including population size thresholds such as the critical community size. The straw-coloured fruit bat, Eidolon helvum, has been identified as a reservoir for henipaviruses (serological evidence) and Lagos bat virus (LBV; virus isolation and serological evidence) in continental Africa. Here, we sampled from a remote population of E. helvum annobonensis fruit bats on Annobón island in the Gulf of Guinea to investigate whether antibodies to these viruses also exist in this isolated subspecies. Henipavirus serological analyses (Luminex multiplexed binding and inhibition assays, virus neutralisation tests and western blots) and lyssavirus serological analyses (LBV: modified Fluorescent Antibody Virus Neutralisation test, LBV and Mokola virus: lentivirus pseudovirus neutralisation assay) were undertaken on 73 and 70 samples respectively. Given the isolation of fruit bats on Annobón and their lack of connectivity with other populations, it was expected that the population size on the island would be too small to allow persistence of viruses that are thought to cause acute and immunising infections. However, the presence of antibodies against henipaviruses was detected using the Luminex binding assay and confirmed using alternative assays. Neutralising antibodies to LBV were detected in one bat using both assays. We demonstrate clear evidence for exposure of multiple individuals to henipaviruses in this remote population of E. helvum annobonensis fruit bats on Annobón island. The situation is less clear for LBV. Seroprevalences to henipaviruses and LBV in Annobón are notably different to those in E. helvum in continental locations studied using the same sampling techniques and assays. Whilst cross-sectional serological studies in wildlife populations cannot provide details on viral dynamics within populations, valuable information on the presence or absence of viruses may be obtained and utilised for informing future studies.",2012 Jan 12,"['Peel, Alison J.', 'Baker, Kate S.', 'Crameri, Gary', 'Barr, Jennifer A.', 'Hayman, David T. S.', 'Wright, Edward', 'Broder, Christopher C.', 'Fernández-Loras, Andrés', 'Fooks, Anthony R.', 'Wang, Lin-Fa', 'Cunningham, Andrew A.', 'Wood, James L. N.']",PLoS One,,,True
b7e0b1aeadb98920f56a14043d2f170833a31ef5,PMC,Perspectives on Immunoglobulins in Colostrum and Milk,http://dx.doi.org/10.3390/nu3040442,PMC3257684,22254105,CC BY,"Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases. The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted, and the mechanisms by which the neonate or adult consuming the milk then gains immunological benefit. The stability of immunoglobulins as they undergo processing in the milk, or undergo digestion in the intestine, is an additional consideration for evaluating the value of milk immunoglobulins. This review summarizes the fundamental knowledge of immunoglobulins found in colostrum, milk, and immune milk.",2011 Apr 14,"['Hurley, Walter L.', 'Theil, Peter K.']",Nutrients,,,True
17bcc640fec147856a5d625a1d17970429665b65,PMC,Vaccination of influenza a virus decreases transmission rates in pigs,http://dx.doi.org/10.1186/1297-9716-42-120,PMC3258204,22185601,CC BY,"Limited information is available on the transmission and spread of influenza virus in pig populations with differing immune statuses. In this study we assessed differences in transmission patterns and quantified the spread of a triple reassortant H1N1 influenza virus in naïve and vaccinated pig populations by estimating the reproduction ratio (R) of infection (i.e. the number of secondary infections caused by an infectious individual) using a deterministic Susceptible-Infectious-Recovered (SIR) model, fitted on experimental data. One hundred and ten pigs were distributed in ten isolated rooms as follows: (i) non-vaccinated (NV), (ii) vaccinated with a heterologous vaccine (HE), and (iii) vaccinated with a homologous inactivated vaccine (HO). The study was run with multiple replicates and for each replicate, an infected non-vaccinated pig was placed with 10 contact pigs for two weeks and transmission of influenza evaluated daily by analyzing individual nasal swabs by RT-PCR. A statistically significant difference between R estimates was observed between vaccinated and non-vaccinated pigs (p < 0.05). A statistically significant reduction in transmission was observed in the vaccinated groups where R (95%CI) was 1 (0.39-2.09) and 0 for the HE and the HO groups respectively, compared to an R(o )value of 10.66 (6.57-16.46) in NV pigs (p < 0.05). Transmission in the HE group was delayed and variable when compared to the NV group and transmission could not be detected in the HO group. Results from this study indicate that influenza vaccines can be used to decrease susceptibility to influenza infection and decrease influenza transmission.",2011 Dec 20,"['Romagosa, Anna', 'Allerson, Matt', 'Gramer, Marie', 'Joo, Han Soo', 'Deen, John', 'Detmer, Susan', 'Torremorell, Montserrat']",Vet Res,,,True
fcf41a33dfcb8326a794806dc8bd7585c7e9e591,PMC,Cryptosporidium infection in a veal calf cohort in France: molecular characterization of species in a longitudinal study,http://dx.doi.org/10.1186/1297-9716-42-116,PMC3259045,22136667,CC BY,"Feces from 142 animals were collected on 15 farms in the region of Brittany, France. Each sample was directly collected from the rectum of the animal and identified with the ear tag number. Animals were sampled three times, at 5, 15 and 22 weeks of age. After DNA extraction from stool samples, nested PCR was performed to amplify partial 18S-rDNA and 60 kDa glycoprotein genes of Cryptosporidium. The parasite was detected on all farms. One hundred out of 142 calves (70.4%) were found to be parasitized by Cryptosporidium. Amplified fragments were sequenced for Cryptosporidium species identification and revealed the presence of C. parvum (43.8%), C. ryanae (28.5%), and C. bovis (27%). One animal was infected with Cryptosporidium ubiquitum. The prevalence of these species was related to the age of the animal. C. parvum caused 86.7% of Cryptosporidium infections in 5-week-old calves but only 1.7% in 15-week-old animals. The analysis of the results showed that animals could be infected successively by C. parvum, C. ryanae, and C. bovis for the study period. C. parvum gp60 genotyping identifies 6 IIa subtypes of which 74.5% were represented by IIaA15G2R1. This work confirms previous studies in other countries showing that zoonotic C. parvum is the dominant species seen in young calves.",2011 Dec 2,"['Follet, Jérôme', 'Guyot, Karine', 'Leruste, Hélène', 'Follet-Dumoulin, Anne', 'Hammouma-Ghelboun, Ourida', 'Certad, Gabriela', 'Dei-Cas, Eduardo', 'Halama, Patrice']",Vet Res,,,True
f85f1c88d5f92b9177f3c652fe643d7f13df947e,PMC,Rapid detection of wheat yellow mosaic virus by reverse transcription loop-mediated isothermal amplification,http://dx.doi.org/10.1186/1743-422X-8-550,PMC3260119,22185375,CC BY,"For the detection of wheat yellow mosaic virus (WYMV), we established a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method. Using Primer Explorer software, four sets of primers were designed and RT-LAMP assay reaction conditions were optimized. The RT-LAMP was performed at different times by four primer sets. Agarose gel analysis showed that WYMV could be detected after 30 min with the primer set III and after 45 min with the other three primer sets, both under the 80-min reaction time. RT-LAMP had the same results with the four primer sets, thus primer set III and 65°C for 80 min reaction were selected for virus detection. There was no significant different when avian myeloblastosis virus (AMV) and moloney murine leukemia virus (M-MLV) RT-LAMP with the four primer sets and M-MLV was chosen due to its relatively cheap price. The result on specificity showed that the assay could amplify WYMV specifically, and the sensitivity comparison showed that the RT-LAMP was 100 times more sensitive than conventional reverse-transcriptase-polymerase chain reaction (RT-PCR). Overall, RT-LAMP was found to be a simple, specific, sensitive, convenient and time-saving method for WYMV detection.",2011 Dec 20,"['Zhang, Zong-Ying', 'Liu, Xiao-Jun', 'Li, Da-Wei', 'Yu, Jia-Lin', 'Han, Cheng-Gui']",Virol J,,,True
98e52cb0b81f381ecd6138f73e6596de35d7566f,PMC,Human SCARB2-Mediated Entry and Endocytosis of EV71,http://dx.doi.org/10.1371/journal.pone.0030507,PMC3260287,22272359,CC BY,"Enterovirus (EV) 71 infection is known to cause hand-foot-and-mouth disease (HFMD) and in severe cases, induces neurological disorders culminating in fatality. An outbreak of EV71 in South East Asia in 1997 affected over 120,000 people and caused neurological disorders in a few individuals. The control of EV71 infection through public health interventions remains minimal and treatments are only symptomatic. Recently, human scavenger receptor class B, member 2 (SCARB2) has been reported to be a cellular receptor of EV71. We expressed human SCARB2 gene in NIH3T3 cells (3T3-SCARB2) to study the mechanisms of EV71 entry and infection. We demonstrated that human SCARB2 serves as a cellular receptor for EV71 entry. Disruption of expression of SCARB2 using siRNAs can interfere EV71 infection and subsequent inhibit the expression of viral capsid proteins in RD and 3T3-SCARB2 but not Vero cells. SiRNAs specific to clathrin or dynamin or chemical inhibitor of clathrin-mediated endocytosis were all capable of interfering with the entry of EV71 into 3T3-SCARB2 cells. On the other hand, caveolin specific siRNA or inhibitors of caveolae-mediated endocytosis had no effect, confirming that only clathrin-mediated pathway was involved in EV71 infection. Endocytosis of EV71 was also found to be pH-dependent requiring endosomal acidification and also required intact membrane cholesterol. In summary, the mechanism of EV71 entry through SCARB2 as the receptor for attachment, and its cellular entry is through a clathrin-mediated and pH-dependent endocytic pathway. This study on the receptor and endocytic mechanisms of EV71 infection is useful for the development of effective medications and prophylactic treatment against the enterovirus.",2012 Jan 17,"['Lin, Yi-Wen', 'Lin, Hsiang-Yin', 'Tsou, Yueh-Liang', 'Chitra, Ebenezer', 'Hsiao, Kuang-Nan', 'Shao, Hsiao-Yun', 'Liu, Chia-Chyi', 'Sia, Charles', 'Chong, Pele', 'Chow, Yen-Hung']",PLoS One,,,True
28b64c3ea5c13cbcaae132a45661fb8bf5c25c62,PMC,The Origin and Evolution of Variable Number Tandem Repeat of CLEC4M Gene in the Global Human Population,http://dx.doi.org/10.1371/journal.pone.0030268,PMC3261175,22279577,CC BY,"CLEC4M is a C-type lectin gene serving as cell adhesion receptor and pathogen recognition receptor. It recognizes several pathogens of important public health concern. In particular, a highly polymorphic variable number tandem repeat (VNTR) at the neck-region of CLEC4M had been associated with genetic predisposition to some infectious diseases. To gain insight into the origin and evolution of this VNTR in CLEC4M, we studied 21 Africans, 20 Middle Easterns, 35 Europeans, 38 Asians, 13 Oceania, and 18 Americans (a total of 290 chromosomes) from the (Human Genome Diversity Panel) HGDP-CEPH panel; these samples covered most of alleles of this VNTR locus present in human populations. We identified a limited number of haplotypes among the basic repeat subunits that is 69 base pairs in length. Only 8 haplotypes were found. Their sequence identities were determined in the 290 chromosomes. VNTR alleles of different repeat length (from 4 to 9 repeats) were analyzed for composition and orientation of these subunits. Our results showed that the subunit configuration of the same repeat number of VNTR locus from different populations were, in fact, virtually identical. It implies that most of the VNTR alleles existed before dispersion of modern humans outside Africa. Further analyses indicate that the present diversity profile of this locus in worldwide populations is generated from the effect of migration of different tribes and neutral evolution. Our findings do not support the hypothesis that the origin of the VNTR alleles were arisen by independent (separate) mutation events and caused by differential allele advantage and natural selection as suggested by previous report based on SNP data.",2012 Jan 18,"['Li, Hui', 'Wang, Jia-Xin', 'Wu, Dong-Dong', 'Wang, Hua-Wei', 'Tang, Nelson Leung-Sang', 'Zhang, Ya-Ping']",PLoS One,,,True
7cc24fe787282c1bc90ccbb2d9c2262a95b7504a,PMC,Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus,http://dx.doi.org/10.1371/journal.pone.0030328,PMC3261190,22279582,CC BY,"Swine influenza is an acute respiratory disease in pigs caused by swine influenza virus (SIV). Highly virulent SIV strains cause mortality of up to 10%. Importantly, pigs have long been considered “mixing vessels” that generate novel influenza viruses with pandemic potential, a constant threat to public health. Since its emergence in 2009 and subsequent pandemic spread, the pandemic (H1N1) 2009 (H1N1pdm) has been detected in pig farms, creating the risk of generating new reassortants and their possible infection of humans. Pathogenesis in SIV or H1N1pdm-infected pigs remains poorly characterized. Proinflammatory and antiviral cytokine responses are considered correlated with the intensity of clinical signs, and swine macrophages are found to be indispensible in effective clearance of SIV from pig lungs. In this study, we report a unique pattern of cytokine responses in swine macrophages infected with H1N1pdm. The roles of mitogen-activated protein (MAP) kinases in the regulation of the host responses were examined. We found that proinflammatory cytokines IL-6, IL-8, IL-10, and TNF-α were significantly induced and their induction was ERK1/2-dependent. IFN-β and IFN-inducible antiviral Mx and 2′5′-OAS were sharply induced, but the inductions were effectively abolished when ERK1/2 was inhibited. Induction of CCL5 (RANTES) was completely inhibited by inhibitors of ERK1/2 and JNK1/2, which appeared also to regulate FasL and TNF-α, critical for apoptosis in pig macrophages. We found that NFκB was activated in H1N1pdm-infected cells, but the activation was suppressed when ERK1/2 was inhibited, indicating there is cross-talk between MAP kinase and NFκB responses in pig macrophages. Our data suggest that MAP kinase may activate NFκB through the induction of RIG-1, which leads to the induction of IFN-β in swine macrophages. Understanding host responses and their underlying mechanisms may help identify venues for effective control of SIV and assist in prevention of future influenza pandemics.",2012 Jan 18,"['Gao, Wei', 'Sun, Wenkui', 'Qu, Bingqian', 'Cardona, Carol J.', 'Powell, Kira', 'Wegner, Marta', 'Shi, Yi', 'Xing, Zheng']",PLoS One,,,True
90a31cc826fade05b0a3670af7a5d47d6f972b07,PMC,Trending Now: Using Social Media to Predict and Track Disease Outbreaks,http://dx.doi.org/10.1289/ehp.120-a30,PMC3261963,22214548,CC0,,2012 Jan 1,"Schmidt, Charles W.",Environ Health Perspect,,,True
cf06138d477edd309f439ae40bf555d5bf63b173,PMC,Methods to infer transmission risk factors in complex outbreak data,http://dx.doi.org/10.1098/rsif.2011.0379,PMC3262428,21831890,CC BY,"Data collected during outbreaks are essential to better understand infectious disease transmission and design effective control strategies. But analysis of such data is challenging owing to the dependency between observations that is typically observed in an outbreak and to missing data. In this paper, we discuss strategies to tackle some of the ongoing challenges in the analysis of outbreak data. We present a relatively generic statistical model for the estimation of transmission risk factors, and discuss algorithms to estimate its parameters for different levels of missing data. We look at the problem of computational times for relatively large datasets and show how they can be reduced by appropriate use of discretization, sufficient statistics and some simple assumptions on the natural history of the disease. We also discuss approaches to integrate parametric model fitting and tree reconstruction methods in coherent statistical analyses. The methods are tested on both real and simulated datasets of large outbreaks in structured populations.",2012 Mar 7,"['Cauchemez, Simon', 'Ferguson, Neil M.']",J R Soc Interface,,,True
c46224620e6c2f039588f57d5133dedd75941da5,PMC,RNA-Seq Based Transcriptional Map of Bovine Respiratory Disease Pathogen “Histophilus somni 2336”,http://dx.doi.org/10.1371/journal.pone.0029435,PMC3262788,22276113,CC BY,"Genome structural annotation, i.e., identification and demarcation of the boundaries for all the functional elements in a genome (e.g., genes, non-coding RNAs, proteins and regulatory elements), is a prerequisite for systems level analysis. Current genome annotation programs do not identify all of the functional elements of the genome, especially small non-coding RNAs (sRNAs). Whole genome transcriptome analysis is a complementary method to identify “novel” genes, small RNAs, regulatory regions, and operon structures, thus improving the structural annotation in bacteria. In particular, the identification of non-coding RNAs has revealed their widespread occurrence and functional importance in gene regulation, stress and virulence. However, very little is known about non-coding transcripts in Histophilus somni, one of the causative agents of Bovine Respiratory Disease (BRD) as well as bovine infertility, abortion, septicemia, arthritis, myocarditis, and thrombotic meningoencephalitis. In this study, we report a single nucleotide resolution transcriptome map of H. somni strain 2336 using RNA-Seq method. The RNA-Seq based transcriptome map identified 94 sRNAs in the H. somni genome of which 82 sRNAs were never predicted or reported in earlier studies. We also identified 38 novel potential protein coding open reading frames that were absent in the current genome annotation. The transcriptome map allowed the identification of 278 operon (total 730 genes) structures in the genome. When compared with the genome sequence of a non-virulent strain 129Pt, a disproportionate number of sRNAs (∼30%) were located in genomic region unique to strain 2336 (∼18% of the total genome). This observation suggests that a number of the newly identified sRNAs in strain 2336 may be involved in strain-specific adaptations.",2012 Jan 20,"['Kumar, Ranjit', 'Lawrence, Mark L.', 'Watt, James', 'Cooksey, Amanda M.', 'Burgess, Shane C.', 'Nanduri, Bindu']",PLoS One,,,True
14b4d32ff078c4db9661a587e43a30a7bf227ed9,PMC,The Paradox of Feline Coronavirus Pathogenesis: A Review,http://dx.doi.org/10.1155/2011/109849,PMC3265210,22312333,CC BY,"Feline coronavirus (FCoV) is an enveloped single-stranded RNA virus, of the family Coronaviridae and the order Nidovirales. FCoV is an important pathogen of wild and domestic cats and can cause a mild or apparently symptomless enteric infection, especially in kittens. FCoV is also associated with a lethal, systemic disease known as feline infectious peritonitis (FIP). Although the precise cause of FIP pathogenesis remains unclear, some hypotheses have been suggested. In this review we present results from different FCoV studies and attempt to elucidate existing theories on the pathogenesis of FCoV infection.",2011 Aug 21,"['Myrrha, Luciana Wanderley', 'Silva, Fernanda Miquelitto Figueira', 'Peternelli, Ethel Fernandes de Oliveira', 'Junior, Abelardo Silva', 'Resende, Maurício', 'de Almeida, Márcia Rogéria']",Adv Virol,,,True
bd44d72a9c41b1c382bd180da10a1f7ef38d2d56,PMC,Retargeting of Viruses to Generate Oncolytic Agents,http://dx.doi.org/10.1155/2012/798526,PMC3265223,22312365,CC BY,"Oncolytic virus therapy is based on the ability of viruses to effectively infect and kill tumor cells without destroying the normal tissues. While some viruses seem to have a natural preference for tumor cells, most viruses require the modification of their tropism to specifically enter and replicate in such cells. This review aims to describe the transductional targeting strategies currently employed to specifically redirect viruses towards surface receptors on tumor cells. Three major strategies can be distinguished; they involve (i) the incorporation of new targeting specificity into a viral surface protein, (ii) the incorporation of a scaffold into a viral surface protein to allow the attachment of targeting moieties, and (iii) the use of bispecific adapters to mediate targeting of a virus to a specified moiety on a tumor cell. Of each strategy key features, advantages and limitations are discussed and examples are given. Because of their potential to cause sustained, multiround infection—a desirable characteristic for eradicating tumors—particular attention is given to viruses engineered to become self-targeted by the genomic expression of a bispecific adapter protein.",2012 Nov 14,"['Verheije, M. H.', 'Rottier, P. J. M.']",Adv Virol,,,True
de01b5c28a44e4d80b38e389342275d0353673e7,PMC,"Human Coronaviruses HCoV-NL63 and HCoV-HKU1 in Hospitalized Children with Acute Respiratory Infections in Beijing, China",http://dx.doi.org/10.1155/2011/129134,PMC3265292,22315599,CC BY,"The human coronaviruses (HCoVs) HCoV-NL63 and HCoV-HKU1 are two recently discovered coronaviruses that circulate widely and are associated with acute respiratory infections (ARI). We detected HCoV-NL63 and HCoV-HKU1 in specimens collected from May 2008 to March 2010 from patients with ARI aged <7.75 years of age attending the Beijing Children's Hospital. Thirty-two (8.4%) and 57 (14.9%) of 382 specimens tested positive for HCoV-NL63 and HCoV-HKU1, respectively, by real-time RT-PCR. Use of a Luminex xTAG RVP Fast kit showed that coinfection with respiratory syncytial virus and parainfluenza 3 virus was common among patients infected with either virus type. In HCoV-HKU1-infected patients, the predominant clinical symptoms were cough, fever, and expectoration. In HCoV-NL63-infected patients they were cough, fever, and rhinorrhea. Phylogenetic studies showed that the HCoV-HKU1 nucleoprotein gene was relatively conserved compared to NCBI reference sequences, while the 1ab gene of HCoV-NL63 showed more variation.",2011 Jul 21,"['Cui, Li-Jin', 'Zhang, Chen', 'Zhang, Ting', 'Lu, Rou-Jian', 'Xie, Zheng-De', 'Zhang, Ling-Lin', 'Liu, Chuan-Yan', 'Zhou, Wei-Min', 'Ruan, Li', 'Ma, Xue-Jun', 'Tan, Wen-Jie']",Adv Virol,,,True
551042ee7c8e1bd9f237a51c666376205c89bb3e,PMC,The Evolutionary Processes of Canine Coronaviruses,http://dx.doi.org/10.1155/2011/562831,PMC3265307,22315601,CC BY,"Since the first identification of the virus in 1971, the disease caused by canine coronavirus (CCoV) has not been adequately investigated, and the role that the virus plays in canine enteric illness has not been well established. Only after the emergence in 2002 of SARS in human has new attention been focused on coronaviruses. As a consequence of the relatively high mutation frequency of RNA-positive stranded viruses, CCoV has evolved and, with the biomolecular techniques developed over the last two decades, new virus strains, serotypes, and subtypes have been identified in infected dogs. Considering the widespread nature of CCoV infections among dog populations, several studies have been carried out, focusing upon the epidemiological relevance of these viruses and underlining the need for further investigation into the biology of CCoVs and into the pathogenetic role of the infections. This paper reports the evolutionary processes of CCoVs with a note onto recent diagnostic methods.",2011 Jul 7,"Pratelli, Annamaria",Adv Virol,,,True
d9eb8ffffee8147c850b00f613a1978c18505580,PMC,Feline and Canine Coronaviruses: Common Genetic and Pathobiological Features,http://dx.doi.org/10.1155/2011/609465,PMC3265309,22312347,CC BY,"A new human coronavirus responsible for severe acute respiratory syndrome (SARS) was identified in 2003, which raised concern about coronaviruses as agents of serious infectious disease. Nevertheless, coronaviruses have been known for about 50 years to be major agents of respiratory, enteric, or systemic infections of domestic and companion animals. Feline and canine coronaviruses are widespread among dog and cat populations, sometimes leading to the fatal diseases known as feline infectious peritonitis (FIP) and pantropic canine coronavirus infection in cats and dogs, respectively. In this paper, different aspects of the genetics, host cell tropism, and pathogenesis of the feline and canine coronaviruses (FCoV and CCoV) will be discussed, with a view to illustrating how study of FCoVs and CCoVs can improve our general understanding of the pathobiology of coronaviruses.",2011 Jul 31,"Le Poder, Sophie",Adv Virol,,,True
79284efbde971538024ccbe888fa90bcd515d45c,PMC,The Effects of Temperature and Relative Humidity on the Viability of the SARS Coronavirus,http://dx.doi.org/10.1155/2011/734690,PMC3265313,22312351,CC BY,"The main route of transmission of SARS CoV infection is presumed to be respiratory droplets. However the virus is also detectable in other body fluids and excreta. The stability of the virus at different temperatures and relative humidity on smooth surfaces were studied. The dried virus on smooth surfaces retained its viability for over 5 days at temperatures of 22–25°C and relative humidity of 40–50%, that is, typical air-conditioned environments. However, virus viability was rapidly lost (>3 log(10)) at higher temperatures and higher relative humidity (e.g., 38°C, and relative humidity of >95%). The better stability of SARS coronavirus at low temperature and low humidity environment may facilitate its transmission in community in subtropical area (such as Hong Kong) during the spring and in air-conditioned environments. It may also explain why some Asian countries in tropical area (such as Malaysia, Indonesia or Thailand) with high temperature and high relative humidity environment did not have major community outbreaks of SARS.",2011 Oct 1,"['Chan, K. H.', 'Peiris, J. S. Malik', 'Lam, S. Y.', 'Poon, L. L. M.', 'Yuen, K. Y.', 'Seto, W. H.']",Adv Virol,,,True
14c756dfe065a0ed1ff950195576f8975d209c93,PMC,Effect modification of environmental factors on influenza-associated mortality: a time-series study in two Chinese cities,http://dx.doi.org/10.1186/1471-2334-11-342,PMC3265445,22168284,CC BY,"BACKGROUND: Environmental factors have been associated with transmission and survival of influenza viruses but no studies have ever explored the role of environmental factors on severity of influenza infection. METHODS: We applied a Poisson regression model to the mortality data of two Chinese metropolitan cities located within the subtropical zone, to calculate the influenza associated excess mortality risks during the periods with different levels of temperature and humidity. RESULTS: The results showed that high absolute humidity (measured by vapor pressure) was significantly (p < 0.05) associated with increased risks of all-cause and cardiorespiratory deaths, but not with increased risks of pneumonia and influenza deaths. The association between absolute humidity and mortality risks was found consistent among the two cities. An increasing pattern of influenza associated mortality risks was also found across the strata of low to high relative humidity, but the results were less consistent for temperature. CONCLUSIONS: These findings highlight the need for people with chronic cardiovascular and respiratory diseases to take extra caution against influenza during hot and humid days in the subtropics and tropics.",2011 Dec 14,"['Yang, Lin', 'Chen, Ping Yan', 'He, Jian Feng', 'Chan, King Pan', 'Ou, Chun Quan', 'Deng, Ai Ping', 'Malik Peiris, JS', 'Wong, Chit Ming']",BMC Infect Dis,,,True
41546fbae5ea1a9c511d17fa9d9b583f944eda95,PMC,Genome Wide Association Identifies PPFIA1 as a Candidate Gene for Acute Lung Injury Risk Following Major Trauma,http://dx.doi.org/10.1371/journal.pone.0028268,PMC3266233,22295056,CC BY,"Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated B-lymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research.",2012 Jan 25,"['Christie, Jason D.', 'Wurfel, Mark M.', 'Feng, Rui', ""O'Keefe, Grant E."", 'Bradfield, Jonathan', 'Ware, Lorraine B.', 'Christiani, David C.', 'Calfee, Carolyn S.', 'Cohen, Mitchell J.', 'Matthay, Michael', 'Meyer, Nuala J.', 'Kim, Cecilia', 'Li, Mingyao', 'Akey, Joshua', 'Barnes, Kathleen C.', 'Sevransky, Jonathan', 'Lanken, Paul N.', 'May, Addison K.', 'Aplenc, Richard', 'Maloney, James P.', 'Hakonarson, Hakon', None]",PLoS One,,,True
84db97911a7abce47876c5732ac570d78f253aaa,PMC,One Health concept for strengthening public health surveillance and response through Field Epidemiology and Laboratory Training in Ghana,,PMC3266674,22359694,CC BY,"The lack of highly trained field epidemiologists in the public health system in Ghana has been known since the 1970s when the Planning Unit was established in the Ghana Ministry of Health. When the Public Health School was started in 1994, the decision was taken to develop a 1 academic-year general MPH course. The persisting need for well-trained epidemiologists to support the public health surveillance, outbreak investigation and response system made the development of the Field Epidemiology and Laboratory Training Programme (FELTP) a national priority. The School of Public health and the Ministry of Health therefore requested the technical and financial assistance of the United States Centers for Disease Control and Prevention (CDC) in organizing the Programme. The collaboration started by organizing short courses in disease outbreak investigations and response for serving Ghana Health Service staff. The success of the short courses led to development of the FELTP. By October 2007, the new FELTP curriculum for the award of a Masters of Philosophy in Applied Epidemiology and Disease Control was approved by the Academic Board of the University of Ghana and the programme started that academic year. Since then five cohorts of 37 residents have been enrolled in the two tracks of the programme. They consist of 12 physicians, 12 veterinarians and 13 laboratory scientists. The first two cohorts of 13 residents have graduated. The third cohort of seven has submitted dissertations and is awaiting the results. The fourth cohort has started the second year of field placement while the fifth cohort has just started the first semester. The field activities of the graduates have included disease outbreak investigations and response, evaluation of disease surveillance systems at the national level and analysis of datasets on diseases at the regional level. The residents have made a total of 25 oral presentations and 39 poster presentations at various regional and global scientific conferences. The Ghana FELTP (GFELTP) has promoted the introduction of the One Health concept into FELTP. It hosted the first USAID–supported workshop in West Africa to further integrate and strengthen collaboration of the animal and human health sectors in the FETP model. GFELTP has also taken the lead in hosting the first AFENET Center for Training in Public Health Leadership and Management, through which the short course on Management for Improving Public Health Interventions was developed for AFENET member countries. The GFELTP pre-tested the Integrated Avian Influenza Outbreak and Pandemic Influenza course in preparation for introducing the materials into the curriculum of other FELTP in the network. The leadership positions to which the graduates of the program have been appointed in the human and animal Public Health Services, improvement in disease surveillance, outbreak investigation and response along with the testimony of the health authorities about their appreciation of the outputs of the graduates at various fora, is a strong indication that the GFELTP is meeting its objectives.",2011 Dec 14,"['Wurapa, Frederick', 'Afari, Ebenezer', 'Ohuabunwo, Chima', 'Sackey, Samuel', 'Clerk, Christine', 'Kwadje, Simon', 'Yebuah, Nathaniel', 'Amankwa, Joseph', 'Amofah, George', 'Appiah-Denkyira, Ebenezer']",Pan Afr Med J,,,True
007bf75961da42a7e0cc8e2855e5c208a5ec65c1,PMC,The Murine Coronavirus Hemagglutinin-esterase Receptor-binding Site: A Major Shift in Ligand Specificity through Modest Changes in Architecture,http://dx.doi.org/10.1371/journal.ppat.1002492,PMC3266934,22291594,CC BY,"The hemagglutinin-esterases (HEs), envelope glycoproteins of corona-, toro- and orthomyxoviruses, mediate reversible virion attachment to O-acetylated sialic acids (O-Ac-Sias). They do so through concerted action of distinct receptor-binding (“lectin”) and receptor-destroying sialate O-acetylesterase (”esterase”) domains. Most HEs target 9-O-acetylated Sias. In one lineage of murine coronaviruses, however, HE esterase substrate and lectin ligand specificity changed dramatically as these viruses evolved to use 4-O-acetylated Sias instead. Here we present the crystal structure of the lectin domain of mouse hepatitis virus (MHV) strain S HE, resolved both in its native state and in complex with a receptor analogue. The data show that the shift from 9-O- to 4-O-Ac-Sia receptor usage primarily entailed a change in ligand binding topology and, surprisingly, only modest changes in receptor-binding site architecture. Our findings illustrate the ease with which viruses can change receptor-binding specificity with potential consequences for host-, organ and/or cell tropism, and for pathogenesis.",2012 Jan 26,"['Langereis, Martijn A.', 'Zeng, Qinghong', 'Heesters, Balthasar', 'Huizinga, Eric G.', 'de Groot, Raoul J.']",PLoS Pathog,,,True
3a6f6369bb9df09d06938f9ef8fdceb72de53a21,PMC,"Detection of human bocavirus from children and adults with acute respiratory tract illness in Guangzhou, southern China",http://dx.doi.org/10.1186/1471-2334-11-345,PMC3267697,22168387,CC BY,"BACKGROUND: Human bocavirus (HBoV) is a newly discovered parvovirus associated with acute respiratory tract illness (ARTI) and gastrointestinal illness. Our study is the first to analyze the characteristics of HBoV-positive samples from ARTI patients with a wide age distribution from Guangzhou, southern China. METHODS: Throat swabs (n=2811) were collected and analyzed from children and adults with ARTI over a 13-month period. The HBoV complete genome from a 60 year-old female patient isolate was also determined. RESULTS: HBoV DNA was detected in 65/2811 (2.3%) samples, of which 61/1797 were from children (<18 years old) and 4/1014 from adults (≥18 years old). Seasonal peaks of 4.8% and 7.7% were detected in May and June, respectively. 28 of 65 (43.1%) HBoV-positive samples were co-detected with 11/16 other potential pathogens. Mycoplasma pneumoniae had the highest frequency of 16.9% (11/65). Upper and lower respiratory tract illness were common symptoms, with 19/65 (29.2%) patients diagnosed with pneumonia by chest radiography. All four adult patients had systemic influenza-like symptoms. Phylogenetic analysis of the complete genome revealed a close relationship with other HBoVs, and a more distant relationship with HBoV2 and HBoV3. CONCLUSIONS: HBoV was detected from children and adults with ARTI from Guangzhou, southern China. Elderly people were also susceptive to HBoV. A single lineage of HBoV was detected among a wide age distribution of patients with ARTI.",2011 Dec 14,"['Liu, Wen-Kuan', 'Chen, De-Hui', 'Liu, Qian', 'Liang, Huan-Xi', 'Yang, Zi-Feng', 'Qin, Sheng', 'Zhou, Rong']",BMC Infect Dis,,,True
ce88c461bd735cb67a9a7f6dc4d3ec1418d7dffb,PMC,Low usage of government healthcare facilities for acute respiratory infections in guatemala: implications for influenza surveillance,http://dx.doi.org/10.1186/1471-2458-11-885,PMC3267779,22111590,CC BY,"BACKGROUND: Sentinel surveillance for severe acute respiratory infections in hospitals and influenza-like illness in ambulatory clinics is recommended to assist in global pandemic influenza preparedness. Healthcare utilization patterns will affect the generalizability of data from sentinel sites and the potential to use them to estimate burden of disease. The objective of this study was to measure healthcare utilization patterns in Guatemala to inform the establishment of a sentinel surveillance system for influenza and other respiratory infections, and allow estimation of disease burden. METHODS: We used a stratified, two-stage cluster survey sample to select 1200 households from the Department of Santa Rosa. Trained interviewers screened household residents for self-reported pneumonia in the last year and influenza-like illness (ILI) in the last month and asked about healthcare utilization for each illness episode. RESULTS: We surveyed 1131 (94%) households and 5449 residents between October and December 2006 and identified 323 (6%) cases of pneumonia and 628 (13%) cases of ILI. Treatment for pneumonia outside the home was sought by 92% of the children <5 years old and 73% of the persons aged five years and older. For both children <5 years old (53%) and persons aged five years and older (31%) who reported pneumonia, private clinics were the most frequently reported source of care. For ILI, treatment was sought outside the home by 81% of children <5 years old and 65% of persons aged five years and older. Government ambulatory clinics were the most frequently sought source of care for ILI both for children <5 years old (41%) and persons aged five years and older (36%). CONCLUSIONS: Sentinel surveillance for influenza and other respiratory infections based in government health facilities in Guatemala will significantly underestimate the burden of disease. Adjustment for healthcare utilization practices will permit more accurate estimation of the incidence of influenza and other respiratory pathogens in the community.",2011 Nov 24,"['Lindblade, Kim A', 'Johnson, April J', 'Arvelo, Wences', 'Zhang, Xingyou', 'Jordan, Hannah T', 'Reyes, Lissette', 'Fry, Alicia M', 'Padilla, Norma']",BMC Public Health,,,True
2f8012db8f2100bb1876e19722d6c131849e2315,PMC,Coronavirus Papain-like Proteases Negatively Regulate Antiviral Innate Immune Response through Disruption of STING-Mediated Signaling,http://dx.doi.org/10.1371/journal.pone.0030802,PMC3270028,22312431,CC BY,"Viruses have evolved elaborate mechanisms to evade or inactivate the complex system of sensors and signaling molecules that make up the host innate immune response. Here we show that human coronavirus (HCoV) NL63 and severe acute respiratory syndrome (SARS) CoV papain-like proteases (PLP) antagonize innate immune signaling mediated by STING (stimulator of interferon genes, also known as MITA/ERIS/MYPS). STING resides in the endoplasmic reticulum and upon activation, forms dimers which assemble with MAVS, TBK-1 and IKKε, leading to IRF-3 activation and subsequent induction of interferon (IFN). We found that expression of the membrane anchored PLP domain from human HCoV-NL63 (PLP2-TM) or SARS-CoV (PLpro-TM) inhibits STING-mediated activation of IRF-3 nuclear translocation and induction of IRF-3 dependent promoters. Both catalytically active and inactive forms of CoV PLPs co-immunoprecipitated with STING, and viral replicase proteins co-localize with STING in HCoV-NL63-infected cells. Ectopic expression of catalytically active PLP2-TM blocks STING dimer formation and negatively regulates assembly of STING-MAVS-TBK1/IKKε complexes required for activation of IRF-3. STING dimerization was also substantially reduced in cells infected with SARS-CoV. Furthermore, the level of ubiquitinated forms of STING, RIG-I, TBK1 and IRF-3 are reduced in cells expressing wild type or catalytic mutants of PLP2-TM, likely contributing to disruption of signaling required for IFN induction. These results describe a new mechanism used by CoVs in which CoV PLPs negatively regulate antiviral defenses by disrupting the STING-mediated IFN induction.",2012 Feb 1,"['Sun, Li', 'Xing, Yaling', 'Chen, Xiaojuan', 'Zheng, Yang', 'Yang, Yudong', 'Nichols, Daniel B.', 'Clementz, Mark A.', 'Banach, Bridget S.', 'Li, Kui', 'Baker, Susan C.', 'Chen, Zhongbin']",PLoS One,,,True
989be59a0cd5354610ff80be6e50fa6617c077bf,PMC,Protective Role of the ACE2/Ang-(1–9) Axis in Cardiovascular Remodeling,http://dx.doi.org/10.1155/2012/594361,PMC3270559,22315665,CC BY,"Despite reduction in cardiovascular (CV) events and end-organ damage with the current pharmacologic strategies, CV disease remains the primary cause of death in the world. Pharmacological therapies based on the renin angiotensin system (RAS) blockade are used extensively for the treatment of hypertension, heart failure, and CV remodeling but in spite of their success the prevalence of end-organ damage and residual risk remain still high. Novel approaches must be discovered for a more effective treatment of residual CV remodeling and risk. The ACE2/Ang-(1–9) axis is a new and important target to counterbalance the vasoconstrictive/proliferative RAS axis. Ang-(1–9) is hydrolyzed slower than Ang-(1–7) and is able to bind the Ang II type 2 receptor. We review here the current experimental evidence suggesting that activation of the ACE2/Ang-(1–9) axis protects the heart and vessels (and possibly the kidney) from adverse cardiovascular remodeling in hypertension as well as in heart failure.",2012 Jan 19,"['Ocaranza, María Paz', 'Jalil, Jorge E.']",Int J Hypertens,,,True
6652151e876145926c6b4c6d683346811588bdfa,PMC,Antiviral activity of four types of bioflavonoid against dengue virus type-2,http://dx.doi.org/10.1186/1743-422X-8-560,PMC3271998,22201648,CC BY,"BACKGROUND: Dengue is a major mosquito-borne disease currently with no effective antiviral or vaccine available. Effort to find antivirals for it has focused on bioflavonoids, a plant-derived polyphenolic compounds with many potential health benefits. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2) in Vero cell was evaluated. Anti-dengue activity of these compounds was determined at different stages of DENV-2 infection and replication cycle. DENV replication was measured by Foci Forming Unit Reduction Assay (FFURA) and quantitative RT-PCR. Selectivity Index value (SI) was determined as the ratio of cytotoxic concentration 50 (CC(50)) to inhibitory concentration 50 (IC(50)) for each compound. RESULTS: The half maximal inhibitory concentration (IC(50)) of quercetin against dengue virus was 35.7 μg mL(-1 )when it was used after virus adsorption to the cells. The IC(50 )decreased to 28.9 μg mL(-1 )when the cells were treated continuously for 5 h before virus infection and up to 4 days post-infection. The SI values for quercetin were 7.07 and 8.74 μg mL(-1), respectively, the highest compared to all bioflavonoids studied. Naringin only exhibited anti-adsorption effects against DENV-2 with IC(50 )= 168.2 μg mL(-1 )and its related SI was 1.3. Daidzein showed a weak anti-dengue activity with IC(50 )= 142.6 μg mL(-1 )when the DENV-2 infected cells were treated after virus adsorption. The SI value for this compound was 1.03. Hesperetin did not exhibit any antiviral activity against DENV-2. The findings obtained from Foci Forming Unit Reduction Assay (FFURA) were corroborated by findings of the qRT-PCR assays. Quercetin and daidzein (50 μg mL(-1)) reduced DENV-2 RNA levels by 67% and 25%, respectively. There was no significant inhibition of DENV-2 RNA levels with naringin and hesperetin. CONCLUSION: Results from the study suggest that only quercetin demonstrated significant anti-DENV-2 inhibitory activities. Other bioflavonoids, including daidzein, naringin and hesperetin showed minimal to no significant inhibition of DENV-2 virus replication. These findings, together with those previously reported suggest that select group of bioflavonoids including quercetin and fisetin, exhibited significant inhibitory activities against dengue virus. This group of flavonoids, flavonol, could be investigated further to discover the common mechanisms of inhibition of dengue virus replication.",2011 Dec 28,"['Zandi, Keivan', 'Teoh, Boon-Teong', 'Sam, Sing-Sin', 'Wong, Pooi-Fong', 'Mustafa, Mohd Rais', 'AbuBakar, Sazaly']",Virol J,,,True
880b3f24a1f3678dd29cb446dae24298863b8676,PMC,New Cardiovascular and Pulmonary Therapeutic Strategies Based on the Angiotensin-Converting Enzyme 2/Angiotensin-(1–7)/Mas Receptor Axis,http://dx.doi.org/10.1155/2012/147825,PMC3272817,22319643,CC BY,"Angiotensin (Ang)-(1–7) is now recognized as a biologically active component of the renin-angiotensin system (RAS). The discovery of the angiotensin-converting enzyme homologue ACE2 revealed important metabolic pathways involved in the Ang-(1–7) synthesis. This enzyme can form Ang-(1–7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1–9) with subsequent Ang-(1–7) formation. Additionally, it is well established that the G protein-coupled receptor Mas is a functional ligand site for Ang-(1–7). The axis formed by ACE2/Ang-(1–7)/Mas represents an endogenous counter regulatory pathway within the RAS whose actions are opposite to the vasoconstrictor/proliferative arm of the RAS constituted by ACE/Ang II/AT(1) receptor. In this review we will discuss recent findings concerning the biological role of the ACE2/Ang-(1–7)/Mas arm in the cardiovascular and pulmonary system. Also, we will highlight the initiatives to develop potential therapeutic strategies based on this axis.",2012 Jan 26,"['Ferreira, Anderson J.', 'Murça, Tatiane M.', 'Fraga-Silva, Rodrigo A.', 'Castro, Carlos Henrique', 'Raizada, Mohan K.', 'Santos, Robson A. S.']",Int J Hypertens,,,True
5a1ae510c59da66b27b5a5a8adf78b252303f9f2,PMC,Fighting Misconceptions to Improve Compliance with Influenza Vaccination among Health Care Workers: An Educational Project,http://dx.doi.org/10.1371/journal.pone.0030670,PMC3273463,22328920,CC BY,"The compliance with influenza vaccination is poor among health care workers (HCWs) due to misconceptions about safety and effectiveness of influenza vaccine. We proposed an educational prospective study to demonstrate to HCWs that influenza vaccine is safe and that other respiratory viruses (RV) are the cause of respiratory symptoms in the months following influenza vaccination. 398 HCWs were surveyed for adverse events (AE) occurring within 48 h of vaccination. AE were reported by 30% of the HCWs. No severe AE was observed. A subset of 337 HCWs was followed up during four months, twice a week, for the detection of respiratory symptoms. RV was diagnosed by direct immunofluorescent assay (DFA) and real time PCR in symptomatic HCWs. Influenza A was detected in five episodes of respiratory symptoms (5.3%) and other RV in 26 (27.9%) episodes. The incidence density of influenza and other RV was 4.3 and 10.8 episodes per 100 HCW-month, respectively. The educational nature of the present study may persuade HCWs to develop a more positive attitude to influenza vaccination.",2012 Feb 6,"['Couto, Carla R.', 'Pannuti, Cláudio S.', 'Paz, José P.', 'Fink, Maria C. D.', 'Machado, Alessandra A.', 'de Marchi, Michela', 'Machado, Clarisse M.']",PLoS One,,,True
56feb53034b99302ba30fa1c3e2042b2118fe6cb,PMC,"Systematic screening for novel, serologically reactive Hepatitis E Virus epitopes",http://dx.doi.org/10.1186/1743-422X-9-28,PMC3274478,22269698,CC BY,"BACKGROUND: The National Institutes of Health classified Hepatitis E as an emerging disease since Hepatitis E Virus (HEV) is the major cause of acute hepatitis in developing countries. Interestingly, an increasing number of sporadic cases of HEV infections are described in industrialized countries as zoonosis from domestic livestock. Despite the increasing relevance of this pathogen in clinical virology, commercial antibody assays are mainly based on fragments of HEV open reading frame (ORF) 2 and ORF3. The largest ORF1 (poly-)protein, however, is not part of current testing formats. METHODS: From a synthesized full length HEV genotype 1 cDNA-bank we constructed a complete HEV gene library consisting of 15 respective HEV ORF domains. After bacterial expression and purification of nine recombinant HEV proteins under denaturating conditions serum profiling experiments using 55 sera from patients with known infection status were performed in microarray format. SPSS software assessed the antigenic potential of these nine ORF domains in comparison to seven commercial HEV antigens (genotype 1 and 3) by performing receiver operator characteristics, logistic regression and correlation analysis. RESULTS: HEV antigens produced with our method for serum profiling experiments exhibit the same quality and characteristics as commercial antigens. Serum profiling experiments detected Y, V and X domains as ORF1-antigens with potentially comparable diagnostic significance as the well established epitopes of ORF2 and ORF3. However no obvious additional increase in sensitivity or specificity was achieved in diagnostic testing as revealed by bioinformatic analysis. Additionally we found that the C-terminal domain of the potential transmembrane protein ORF3 is responsible for IgG and IgM seroreactivity. Data suggest that there might be a genotype specific seroreactivity of homologous ORF2-antigens. CONCLUSIONS: The diagnostic value of identified ORF1 epitopes might not necessarily improve sensitivity and specificity, but broaden the overall quality of existing test systems. ORF2 and ORF3-antigens are still commonly used in diagnostic assays and possibly hold the potential to serologically differentiate between genotype 1 and 3 infections. Our systematic approach is a suitable method to investigate HEV domains for their serologic antigenicity. Epitope screening of native viral domains could be a preferable tool in developing new serologic test components.",2012 Jan 23,"['Osterman, Andreas', 'Vizoso Pinto, Maria Guadalupe', 'Haase, Rudolf', 'Nitschko, Hans', 'Jäger, Simone', 'Sander, Michaela', 'Motz, Manfred', 'Mohn, Ulrich', 'Baiker, Armin']",Virol J,,,True
9692bb55e1e2eec083333ee2139137e6ddf3a4d8,PMC,Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing,http://dx.doi.org/10.1371/journal.pntd.0001485,PMC3274504,22347512,CC BY,"Dengue virus is an emerging infectious agent that infects an estimated 50–100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ∼40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness.",2012 Feb 7,"['Yozwiak, Nathan L.', 'Skewes-Cox, Peter', 'Stenglein, Mark D.', 'Balmaseda, Angel', 'Harris, Eva', 'DeRisi, Joseph L.']",PLoS Negl Trop Dis,,,True
71d23a3d11c102af8346110435fc8e188665e832,PMC,Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing,http://dx.doi.org/10.1371/journal.pntd.0001485,PMC3274504,22347512,CC BY,"Dengue virus is an emerging infectious agent that infects an estimated 50–100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ∼40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness.",2012 Feb 7,"['Yozwiak, Nathan L.', 'Skewes-Cox, Peter', 'Stenglein, Mark D.', 'Balmaseda, Angel', 'Harris, Eva', 'DeRisi, Joseph L.']",PLoS Negl Trop Dis,,,False
e21d9c0b64186b32a1afed5223bfa4e879574cb7,PMC,Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing,http://dx.doi.org/10.1371/journal.pntd.0001485,PMC3274504,22347512,CC BY,"Dengue virus is an emerging infectious agent that infects an estimated 50–100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ∼40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness.",2012 Feb 7,"['Yozwiak, Nathan L.', 'Skewes-Cox, Peter', 'Stenglein, Mark D.', 'Balmaseda, Angel', 'Harris, Eva', 'DeRisi, Joseph L.']",PLoS Negl Trop Dis,,,False
3c2f8d1ce0724ee7966c5647836bd996a79c9205,PMC,Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing,http://dx.doi.org/10.1371/journal.pntd.0001485,PMC3274504,22347512,CC BY,"Dengue virus is an emerging infectious agent that infects an estimated 50–100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ∼40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness.",2012 Feb 7,"['Yozwiak, Nathan L.', 'Skewes-Cox, Peter', 'Stenglein, Mark D.', 'Balmaseda, Angel', 'Harris, Eva', 'DeRisi, Joseph L.']",PLoS Negl Trop Dis,,,False
400d3287bd63bba9d2a3fe69308c6c1795baebad,PMC,Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing,http://dx.doi.org/10.1371/journal.pntd.0001485,PMC3274504,22347512,CC BY,"Dengue virus is an emerging infectious agent that infects an estimated 50–100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ∼40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness.",2012 Feb 7,"['Yozwiak, Nathan L.', 'Skewes-Cox, Peter', 'Stenglein, Mark D.', 'Balmaseda, Angel', 'Harris, Eva', 'DeRisi, Joseph L.']",PLoS Negl Trop Dis,,,False
e1ae1fce6ed744522728aef322c22b5f239b9157,PMC,Effects of a Non-Conservative Sequence on the Properties of β-glucuronidase from Aspergillus terreus Li-20,http://dx.doi.org/10.1371/journal.pone.0030998,PMC3274521,22347419,CC BY,"We cloned the β-glucuronidase gene (AtGUS) from Aspergillus terreus Li-20 encoding 657 amino acids (aa), which can transform glycyrrhizin into glycyrrhetinic acid monoglucuronide (GAMG) and glycyrrhetinic acid (GA). Based on sequence alignment, the C-terminal non-conservative sequence showed low identity with those of other species; thus, the partial sequence AtGUS(-3t) (1–592 aa) was amplified to determine the effects of the non-conservative sequence on the enzymatic properties. AtGUS and AtGUS(-3t) were expressed in E. coli BL21, producing AtGUS-E and AtGUS(-3t)-E, respectively. At the similar optimum temperature (55°C) and pH (AtGUS-E, 6.6; AtGUS(-3t)-E, 7.0) conditions, the thermal stability of AtGUS(-3t)-E was enhanced at 65°C, and the metal ions Co(2+), Ca(2+) and Ni(2+) showed opposite effects on AtGUS-E and AtGUS(-3t)-E, respectively. Furthermore, Km of AtGUS(-3t)-E (1.95 mM) was just nearly one-seventh that of AtGUS-E (12.9 mM), whereas the catalytic efficiency of AtGUS(-3t)-E was 3.2 fold higher than that of AtGUS-E (7.16 vs. 2.24 mM s(−1)), revealing that the truncation of non-conservative sequence can significantly improve the catalytic efficiency of AtGUS. Conformational analysis illustrated significant difference in the secondary structure between AtGUS-E and AtGUS(-3t)-E by circular dichroism (CD). The results showed that the truncation of the non-conservative sequence could preferably alter and influence the stability and catalytic efficiency of enzyme.",2012 Feb 7,"['Liu, Yanli', 'Huangfu, Jie', 'Qi, Feng', 'Kaleem, Imdad', 'E, Wenwen', 'Li, Chun']",PLoS One,,,True
69bce356ec4ad3fcc2a0d7ba9ecfaf0d90d8e423,PMC,Composite Structural Motifs of Binding Sites for Delineating Biological Functions of Proteins,http://dx.doi.org/10.1371/journal.pone.0031437,PMC3275580,22347478,CC BY,"Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs that represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures.",2012 Feb 8,"['Kinjo, Akira R.', 'Nakamura, Haruki']",PLoS One,,,True
8ed7e985c1bef92952d4626090ac1c31c9566a23,PMC,"Understanding community perceptions, social norms and current practice related to respiratory infection in Bangladesh during 2009: a qualitative formative study",http://dx.doi.org/10.1186/1471-2458-11-901,PMC3276487,22136080,CC BY,"BACKGROUND: Respiratory infections are the leading cause of childhood deaths in Bangladesh. Promoting respiratory hygiene may reduce infection transmission. This formative research explored community perceptions about respiratory infections. METHODS: We conducted 34 in-depth interviews and 16 focus group discussions with community members and school children to explore respiratory hygiene related perceptions, practices, and social norms in an urban and a rural setting. We conducted unstructured observations on respiratory hygiene practices in public markets. RESULTS: Informants were not familiar with the term ""respiratory infection""; most named diseases that had no relation to respiratory dysfunction. Informants reported that their community identified a number of 'good behaviors' related to respiratory hygiene, but they also noted, and we observed, that very few people practiced these. All informants cited hot/cold weather changes or using cold water as causes for catching cold. They associated transmission of respiratory infections with close contact with a sick person's breath, cough droplets, or spit; sharing a sick person's utensils and food. Informants suggested that avoiding such contact was the most effective method to prevent respiratory infection. Although informants perceived that handwashing after coughing or sneezing might prevent illness, they felt this was not typically feasible or practical. CONCLUSION: Community perceptions of respiratory infections include both concerns with imbalances between hot and cold, and with person-to-person transmission. Many people were aware of measures that could prevent respiratory infection, but did not practice them. Interventions that leverage community understanding of person-to-person transmission and that encourage the practice of their identified 'good behaviors' related to respiratory hygiene may reduce respiratory disease transmission.",2011 Dec 4,"['Nizame, Fosiul A', 'Nasreen, Sharifa', 'Unicomb, Leanne', 'Southern, Dorothy', 'Gurley, Emily S', 'Arman, Shaila', 'Kadir, Mohammad A', 'Azziz-Baumgartner, Eduardo', 'Luby, Stephen P', 'Winch, Peter J']",BMC Public Health,,,True
09403dce0f0c10723150a14e1ea2f00b11dc05fb,PMC,Evaluation of a Web-Based Intervention to Promote Hand Hygiene: Exploratory Randomized Controlled Trial,http://dx.doi.org/10.2196/jmir.1963,PMC3278093,22155673,CC BY,"BACKGROUND: Hand-washing is regarded as a potentially important behavior for preventing transmission of respiratory infection, particularly during a pandemic. OBJECTIVE: The objective of our study was to evaluate whether a Web-based intervention can encourage more frequent hand-washing in the home, and to examine potential mediators and moderators of outcomes, as a necessary first step before testing effects of the intervention on infection rates in the PRIMIT trial (PRimary care trial of a website based Infection control intervention to Modify Influenza-like illness and respiratory infection Transmission). METHODS: In a parallel-group pragmatic exploratory trial design, 517 nonblinded adults recruited through primary care were automatically randomly assigned to a fully automated intervention comprising 4 sessions of tailored motivational messages and self-regulation support (n = 324) or to a no-intervention control group (n = 179; ratio 2:1). Hand-washing frequency and theory of planned behavior cognitions relating to hand-washing were assessed by online questionnaires at baseline (in only half of the control participants, to permit evaluation of effects of baseline assessment on effect sizes), at 4 weeks (postintervention; all participants), and at 12 weeks. RESULTS: Hand-washing rates in the intervention group were higher at 4 weeks than in the control group (mean 4.40, n = 285 and mean 4.04, n = 157, respectively; P < .001, Cohen d = 0.42) and remained higher at 12 weeks (mean 4.45, n = 282 and mean 4.12, n = 154, respectively; P < .001, Cohen d = 0.34). Hand-washing intentions and positive attitudes toward hand-washing increased more from baseline to 4 weeks in the intervention group than in the control group. Mediation analyses revealed positive indirect effects of the intervention on change in hand-washing via intentions (coefficient = .15, 95% confidence interval [CI], .08–.26) and attitudes (coefficient = 0.16, 95% CI, .09–.26). Moderator analyses confirmed that the intervention was similarly effective for men and women, those of higher and lower socioeconomic status, and those with higher and lower levels of perceived risk. CONCLUSIONS: This study provides promising evidence that Web-based interventions could potentially provide an effective method of promoting hand hygiene in the home. Data were collected during the 2010 influenza pandemic, when participants in both groups had already been exposed to extensive publicity about the need for hand hygiene, suggesting that our intervention could add to existing public health campaigns. However, further research is required to determine the effects of the intervention on actual infection rates. TRIAL: International Standard Randomized Controlled Trial Number (ISRCTN): 75058295; http://www.controlled-trials.com/ISRCTN75058295 (Archived by WebCite at http://www.webcitation.org/62KSbkNmm)",2011 Dec 9,"['Yardley, Lucy', 'Miller, Sascha', 'Schlotz, Wolff', 'Little, Paul']",J Med Internet Res,,,True
6feb6f6d40f0c7540336a923c65c53a88afad147,PMC,Evaluation of a Web-Based Intervention to Promote Hand Hygiene: Exploratory Randomized Controlled Trial,http://dx.doi.org/10.2196/jmir.1963,PMC3278093,22155673,CC BY,"BACKGROUND: Hand-washing is regarded as a potentially important behavior for preventing transmission of respiratory infection, particularly during a pandemic. OBJECTIVE: The objective of our study was to evaluate whether a Web-based intervention can encourage more frequent hand-washing in the home, and to examine potential mediators and moderators of outcomes, as a necessary first step before testing effects of the intervention on infection rates in the PRIMIT trial (PRimary care trial of a website based Infection control intervention to Modify Influenza-like illness and respiratory infection Transmission). METHODS: In a parallel-group pragmatic exploratory trial design, 517 nonblinded adults recruited through primary care were automatically randomly assigned to a fully automated intervention comprising 4 sessions of tailored motivational messages and self-regulation support (n = 324) or to a no-intervention control group (n = 179; ratio 2:1). Hand-washing frequency and theory of planned behavior cognitions relating to hand-washing were assessed by online questionnaires at baseline (in only half of the control participants, to permit evaluation of effects of baseline assessment on effect sizes), at 4 weeks (postintervention; all participants), and at 12 weeks. RESULTS: Hand-washing rates in the intervention group were higher at 4 weeks than in the control group (mean 4.40, n = 285 and mean 4.04, n = 157, respectively; P < .001, Cohen d = 0.42) and remained higher at 12 weeks (mean 4.45, n = 282 and mean 4.12, n = 154, respectively; P < .001, Cohen d = 0.34). Hand-washing intentions and positive attitudes toward hand-washing increased more from baseline to 4 weeks in the intervention group than in the control group. Mediation analyses revealed positive indirect effects of the intervention on change in hand-washing via intentions (coefficient = .15, 95% confidence interval [CI], .08–.26) and attitudes (coefficient = 0.16, 95% CI, .09–.26). Moderator analyses confirmed that the intervention was similarly effective for men and women, those of higher and lower socioeconomic status, and those with higher and lower levels of perceived risk. CONCLUSIONS: This study provides promising evidence that Web-based interventions could potentially provide an effective method of promoting hand hygiene in the home. Data were collected during the 2010 influenza pandemic, when participants in both groups had already been exposed to extensive publicity about the need for hand hygiene, suggesting that our intervention could add to existing public health campaigns. However, further research is required to determine the effects of the intervention on actual infection rates. TRIAL: International Standard Randomized Controlled Trial Number (ISRCTN): 75058295; http://www.controlled-trials.com/ISRCTN75058295 (Archived by WebCite at http://www.webcitation.org/62KSbkNmm)",2011 Dec 9,"['Yardley, Lucy', 'Miller, Sascha', 'Schlotz, Wolff', 'Little, Paul']",J Med Internet Res,,,False
1575931c6fe7aea67ea3ced0ebe1df4d2604864c,PMC,Evaluation of a Web-Based Intervention to Promote Hand Hygiene: Exploratory Randomized Controlled Trial,http://dx.doi.org/10.2196/jmir.1963,PMC3278093,22155673,CC BY,"BACKGROUND: Hand-washing is regarded as a potentially important behavior for preventing transmission of respiratory infection, particularly during a pandemic. OBJECTIVE: The objective of our study was to evaluate whether a Web-based intervention can encourage more frequent hand-washing in the home, and to examine potential mediators and moderators of outcomes, as a necessary first step before testing effects of the intervention on infection rates in the PRIMIT trial (PRimary care trial of a website based Infection control intervention to Modify Influenza-like illness and respiratory infection Transmission). METHODS: In a parallel-group pragmatic exploratory trial design, 517 nonblinded adults recruited through primary care were automatically randomly assigned to a fully automated intervention comprising 4 sessions of tailored motivational messages and self-regulation support (n = 324) or to a no-intervention control group (n = 179; ratio 2:1). Hand-washing frequency and theory of planned behavior cognitions relating to hand-washing were assessed by online questionnaires at baseline (in only half of the control participants, to permit evaluation of effects of baseline assessment on effect sizes), at 4 weeks (postintervention; all participants), and at 12 weeks. RESULTS: Hand-washing rates in the intervention group were higher at 4 weeks than in the control group (mean 4.40, n = 285 and mean 4.04, n = 157, respectively; P < .001, Cohen d = 0.42) and remained higher at 12 weeks (mean 4.45, n = 282 and mean 4.12, n = 154, respectively; P < .001, Cohen d = 0.34). Hand-washing intentions and positive attitudes toward hand-washing increased more from baseline to 4 weeks in the intervention group than in the control group. Mediation analyses revealed positive indirect effects of the intervention on change in hand-washing via intentions (coefficient = .15, 95% confidence interval [CI], .08–.26) and attitudes (coefficient = 0.16, 95% CI, .09–.26). Moderator analyses confirmed that the intervention was similarly effective for men and women, those of higher and lower socioeconomic status, and those with higher and lower levels of perceived risk. CONCLUSIONS: This study provides promising evidence that Web-based interventions could potentially provide an effective method of promoting hand hygiene in the home. Data were collected during the 2010 influenza pandemic, when participants in both groups had already been exposed to extensive publicity about the need for hand hygiene, suggesting that our intervention could add to existing public health campaigns. However, further research is required to determine the effects of the intervention on actual infection rates. TRIAL: International Standard Randomized Controlled Trial Number (ISRCTN): 75058295; http://www.controlled-trials.com/ISRCTN75058295 (Archived by WebCite at http://www.webcitation.org/62KSbkNmm)",2011 Dec 9,"['Yardley, Lucy', 'Miller, Sascha', 'Schlotz, Wolff', 'Little, Paul']",J Med Internet Res,,,True
df7ce7b791dbb8848b6222b823622cc5866f681e,PMC,Variability in transmissibility of the 2009 H1N1 pandemic in Canadian communities,http://dx.doi.org/10.1186/1756-0500-4-537,PMC3278401,22166307,CC BY,"BACKGROUND: The prevalence and severity of the 2009 H1N1 pandemic appeared to vary significantly across populations and geographic regions. We sought to investigate the variability in transmissibility of H1N1 pandemic in different health regions (including urban centres and remote, isolated communities) in the province of Manitoba, Canada. METHODS: The Richards model was used to fit to the daily number of laboratory-confirmed cases and estimate transmissibility (referred to as the basic reproduction number, R(0)), doubling times, and turning points of outbreaks in both spring and fall waves of the H1N1 pandemic in several health regions. RESULTS: We observed considerable variation in R(0 )estimates ranging from 1.55 to 2.24, with confidence intervals ranging from 1.45 to 2.88, for an average generation time of 2.9 days, and shorter doubling times in some remote and isolated communities compared to urban centres, suggesting a more rapid spread of disease in these communities during the first wave. For the second wave, R(e), the effective reproduction number, is estimated to be lower for remote and isolated communities; however, outbreaks appear to have been driven by somewhat higher transmissibility in urban centres. CONCLUSIONS: There was considerable geographic variation in transmissibility of the 2009 pandemic outbreaks. While highlighting the importance of estimating R(0 )for informing health responses, the findings indicate that projecting the transmissibility for large-scale epidemics may not faithfully characterize the early spread of disease in remote and isolated communities.",2011 Dec 13,"['Mostaço-Guidolin, Luiz C', 'Greer, Amy', 'Sander, Beate', 'Wu, Jianhong', 'Moghadas, Seyed M']",BMC Res Notes,,,True
35fa07c7c7d1803f22859f6647d5d743e7ad7652,PMC,In silico approach to screen compounds active against parasitic nematodes of major socio-economic importance,http://dx.doi.org/10.1186/1471-2105-12-S13-S25,PMC3278842,22373185,CC BY,"BACKGROUND: Infections due to parasitic nematodes are common causes of morbidity and fatality around the world especially in developing nations. At present however, there are only three major classes of drugs for treating human nematode infections. Additionally the scientific knowledge on the mechanism of action and the reason for the resistance to these drugs is poorly understood. Commercial incentives to design drugs that are endemic to developing countries are limited therefore, virtual screening in academic settings can play a vital role is discovering novel drugs useful against neglected diseases. In this study we propose to build robust machine learning model to classify and screen compounds active against parasitic nematodes. RESULTS: A set of compounds active against parasitic nematodes were collated from various literature sources including PubChem while the inactive set was derived from DrugBank database. The support vector machine (SVM) algorithm was used for model development, and stratified ten-fold cross validation was used to evaluate the performance of each classifier. The best results were obtained using the radial basis function kernel. The SVM method achieved an accuracy of 81.79% on an independent test set. Using the model developed above, we were able to indentify novel compounds with potential anthelmintic activity. CONCLUSION: In this study, we successfully present the SVM approach for predicting compounds active against parasitic nematodes which suggests the effectiveness of computational approaches for antiparasitic drug discovery. Although, the accuracy obtained is lower than the previously reported in a similar study but we believe that our model is more robust because we intentionally employed stringent criteria to select inactive dataset thus making it difficult for the model to classify compounds. The method presents an alternative approach to the existing traditional methods and may be useful for predicting hitherto novel anthelmintic compounds.",2011 Nov 30,"['Khanna, Varun', 'Ranganathan, Shoba']",BMC Bioinformatics,,,True
2f8c155ac0b65122bf485baf2bd6c2fe78e21373,PMC,"Characterization of the Viral Microbiome in Patients with Severe Lower Respiratory Tract Infections, Using Metagenomic Sequencing",http://dx.doi.org/10.1371/journal.pone.0030875,PMC3280267,22355331,CC BY,"The human respiratory tract is heavily exposed to microorganisms. Viral respiratory tract pathogens, like RSV, influenza and rhinoviruses cause major morbidity and mortality from respiratory tract disease. Furthermore, as viruses have limited means of transmission, viruses that cause pathogenicity in other tissues may be transmitted through the respiratory tract. It is therefore important to chart the human virome in this compartment. We have studied nasopharyngeal aspirate samples submitted to the Karolinska University Laboratory, Stockholm, Sweden from March 2004 to May 2005 for diagnosis of respiratory tract infections. We have used a metagenomic sequencing strategy to characterize viruses, as this provides the most unbiased view of the samples. Virus enrichment followed by 454 sequencing resulted in totally 703,790 reads and 110,931 of these were found to be of viral origin by using an automated classification pipeline. The snapshot of the respiratory tract virome of these 210 patients revealed 39 species and many more strains of viruses. Most of the viral sequences were classified into one of three major families; Paramyxoviridae, Picornaviridae or Orthomyxoviridae. The study also identified one novel type of Rhinovirus C, and identified a number of previously undescribed viral genetic fragments of unknown origin.",2012 Feb 15,"['Lysholm, Fredrik', 'Wetterbom, Anna', 'Lindau, Cecilia', 'Darban, Hamid', 'Bjerkner, Annelie', 'Fahlander, Kristina', 'Lindberg, A. Michael', 'Persson, Bengt', 'Allander, Tobias', 'Andersson, Björn']",PLoS One,,,True
24b20768feb528be2a620b4afcd761cdfabcb183,PMC,The Human Antibody Response to Dengue Virus Infection,http://dx.doi.org/10.3390/v3122374,PMC3280510,22355444,CC BY,"Dengue viruses (DENV) are the causative agents of dengue fever (DF) and dengue hemorrhagic fever (DHF). Here we review the current state of knowledge about the human antibody response to dengue and identify important knowledge gaps. A large body of work has demonstrated that antibodies can neutralize or enhance DENV infection. Investigators have mainly used mouse monoclonal antibodies (MAbs) to study interactions between DENV and antibodies. These studies indicate that antibody neutralization of DENVs is a “multi-hit” phenomenon that requires the binding of multiple antibodies to neutralize a virion. The most potently neutralizing mouse MAbs bind to surface exposed epitopes on domain III of the dengue envelope (E) protein. One challenge facing the dengue field now is to extend these studies with mouse MAbs to better understand the human antibody response. The human antibody response is complex as it involves a polyclonal response to primary and secondary infections with 4 different DENV serotypes. Here we review studies conducted with immune sera and MAbs isolated from people exposed to dengue infections. Most dengue-specific antibodies in human immune sera are weakly neutralizing and bind to multiple DENV serotypes. The human antibodies that potently and type specifically neutralize DENV represent a small fraction of the total DENV-specific antibody response. Moreover, these neutralizing antibodies appear to bind to novel epitopes including complex, quaternary epitopes that are only preserved on the intact virion. These studies establish that human and mouse antibodies recognize distinct epitopes on the dengue virion. The leading theory proposed to explain the increased risk of severe disease in secondary cases is antibody dependent enhancement (ADE), which postulates that weakly neutralizing antibodies from the first infection bind to the second serotype and enhance infection of FcγR bearing myeloid cells such as monocytes and macrophages. Here we review results from human, animal and cell culture studies relevant to the ADE hypothesis. By understanding how human antibodies neutralize or enhance DENV, it will be possible to better evaluate existing vaccines and develop the next generation of novel vaccines.",2011 Nov 25,"['Wahala, Wahala M. P. B.', 'de Silva, Aravinda M.']",Viruses,,,True
0e82e56decffd22f29d8229da88e38840404ae37,PMC,Replication-Competent Recombinant Porcine Reproductive and Respiratory Syndrome (PRRS) Viruses Expressing Indicator Proteins and Antiviral Cytokines,http://dx.doi.org/10.3390/v4010102,PMC3280517,22355454,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) can subvert early innate immunity, which leads to ineffective antimicrobial responses. Overcoming immune subversion is critical for developing vaccines and other measures to control this devastating swine virus. The overall goal of this work was to enhance innate and adaptive immunity following vaccination through the expression of interferon (IFN) genes by the PRRSV genome. We have constructed a series of recombinant PRRS viruses using an infectious PRRSV cDNA clone (pCMV-P129). Coding regions of exogenous genes, which included Renilla luciferase (Rluc), green and red fluorescent proteins (GFP and DsRed, respectively) and several interferons (IFNs), were constructed and expressed through a unique subgenomic mRNA placed between ORF1b and ORF2 of the PRRSV infectious clone. The constructs, which expressed Rluc, GFP, DsRed, efficiently produced progeny viruses and mimicked the parental virus in both MARC-145 cells and porcine macrophages. In contrast, replication of IFN-expressing viruses was attenuated, similar to the level of replication observed after the addition of exogenous IFN. Furthermore, the IFN expressing viruses inhibited the replication of a second PRRS virus co-transfected or co-infected. Inhibition by the different IFN subtypes corresponded to their anti-PRRSV activity, i.e., IFNω5 ° IFNα1 > IFN-β > IFNδ3. In summary, the indicator-expressing viruses provided an efficient means for real-time monitoring of viral replication thus allowing high‑throughput elucidation of the role of host factors in PRRSV infection. This was shown when they were used to clearly demonstrate the involvement of tumor susceptibility gene 101 (TSG101) in the early stage of PRRSV infection. In addition, replication‑competent IFN-expressing viruses may be good candidates for development of modified live virus (MLV) vaccines, which are capable of reversing subverted innate immune responses and may induce more effective adaptive immunity against PRRSV infection.",2012 Jan 18,"['Sang, Yongming', 'Shi, Jishu', 'Sang, Wenjing', 'Rowland, Raymond R. R.', 'Blecha, Frank']",Viruses,,,True
30589bfb622ec85458e9bde716261ca00f8b342d,PMC,Replication-Competent Recombinant Porcine Reproductive and Respiratory Syndrome (PRRS) Viruses Expressing Indicator Proteins and Antiviral Cytokines,http://dx.doi.org/10.3390/v4010102,PMC3280517,22355454,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) can subvert early innate immunity, which leads to ineffective antimicrobial responses. Overcoming immune subversion is critical for developing vaccines and other measures to control this devastating swine virus. The overall goal of this work was to enhance innate and adaptive immunity following vaccination through the expression of interferon (IFN) genes by the PRRSV genome. We have constructed a series of recombinant PRRS viruses using an infectious PRRSV cDNA clone (pCMV-P129). Coding regions of exogenous genes, which included Renilla luciferase (Rluc), green and red fluorescent proteins (GFP and DsRed, respectively) and several interferons (IFNs), were constructed and expressed through a unique subgenomic mRNA placed between ORF1b and ORF2 of the PRRSV infectious clone. The constructs, which expressed Rluc, GFP, DsRed, efficiently produced progeny viruses and mimicked the parental virus in both MARC-145 cells and porcine macrophages. In contrast, replication of IFN-expressing viruses was attenuated, similar to the level of replication observed after the addition of exogenous IFN. Furthermore, the IFN expressing viruses inhibited the replication of a second PRRS virus co-transfected or co-infected. Inhibition by the different IFN subtypes corresponded to their anti-PRRSV activity, i.e., IFNω5 ° IFNα1 > IFN-β > IFNδ3. In summary, the indicator-expressing viruses provided an efficient means for real-time monitoring of viral replication thus allowing high‑throughput elucidation of the role of host factors in PRRSV infection. This was shown when they were used to clearly demonstrate the involvement of tumor susceptibility gene 101 (TSG101) in the early stage of PRRSV infection. In addition, replication‑competent IFN-expressing viruses may be good candidates for development of modified live virus (MLV) vaccines, which are capable of reversing subverted innate immune responses and may induce more effective adaptive immunity against PRRSV infection.",2012 Jan 18,"['Sang, Yongming', 'Shi, Jishu', 'Sang, Wenjing', 'Rowland, Raymond R. R.', 'Blecha, Frank']",Viruses,,,False
412833ef524797198177f582425f82e45c0f7a06,PMC,A Co-Opted DEAD-Box RNA Helicase Enhances Tombusvirus Plus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1002537,PMC3280988,22359508,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. In this paper, we show that an essential translation factor, Ded1p DEAD-box RNA helicase of yeast, directly affects replication of Tomato bushy stunt virus (TBSV). To separate the role of Ded1p in viral protein translation from its putative replication function, we utilized a cell-free TBSV replication assay and recombinant Ded1p. The in vitro data show that Ded1p plays a role in enhancing plus-strand synthesis by the viral replicase. We also find that Ded1p is a component of the tombusvirus replicase complex and Ded1p binds to the 3′-end of the viral minus-stranded RNA. The data obtained with wt and ATPase deficient Ded1p mutants support the model that Ded1p unwinds local structures at the 3′-end of the TBSV (−)RNA, rendering the RNA compatible for initiation of (+)-strand synthesis. Interestingly, we find that Ded1p and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is another host factor for TBSV, play non-overlapping functions to enhance (+)-strand synthesis. Altogether, the two host factors enhance TBSV replication synergistically by interacting with the viral (−)RNA and the replication proteins. In addition, we have developed an in vitro assay for Flock house virus (FHV), a small RNA virus of insects, that also demonstrated positive effect on FHV replicase activity by the added Ded1p helicase. Thus, two small RNA viruses, which do not code for their own helicases, seems to recruit a host RNA helicase to aid their replication in infected cells.",2012 Feb 16,"['Kovalev, Nikolay', 'Pogany, Judit', 'Nagy, Peter D.']",PLoS Pathog,,,True
4a07858e23c845b36af362b5dc31af7993fbca56,PMC,A Co-Opted DEAD-Box RNA Helicase Enhances Tombusvirus Plus-Strand Synthesis,http://dx.doi.org/10.1371/journal.ppat.1002537,PMC3280988,22359508,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. In this paper, we show that an essential translation factor, Ded1p DEAD-box RNA helicase of yeast, directly affects replication of Tomato bushy stunt virus (TBSV). To separate the role of Ded1p in viral protein translation from its putative replication function, we utilized a cell-free TBSV replication assay and recombinant Ded1p. The in vitro data show that Ded1p plays a role in enhancing plus-strand synthesis by the viral replicase. We also find that Ded1p is a component of the tombusvirus replicase complex and Ded1p binds to the 3′-end of the viral minus-stranded RNA. The data obtained with wt and ATPase deficient Ded1p mutants support the model that Ded1p unwinds local structures at the 3′-end of the TBSV (−)RNA, rendering the RNA compatible for initiation of (+)-strand synthesis. Interestingly, we find that Ded1p and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is another host factor for TBSV, play non-overlapping functions to enhance (+)-strand synthesis. Altogether, the two host factors enhance TBSV replication synergistically by interacting with the viral (−)RNA and the replication proteins. In addition, we have developed an in vitro assay for Flock house virus (FHV), a small RNA virus of insects, that also demonstrated positive effect on FHV replicase activity by the added Ded1p helicase. Thus, two small RNA viruses, which do not code for their own helicases, seems to recruit a host RNA helicase to aid their replication in infected cells.",2012 Feb 16,"['Kovalev, Nikolay', 'Pogany, Judit', 'Nagy, Peter D.']",PLoS Pathog,,,False
1868242435edf92a6b0018f2569c2012f672ddf7,PMC,Hemagglutinin from the H5N1 Virus Activates Janus Kinase 3 to Dysregulate Innate Immunity,http://dx.doi.org/10.1371/journal.pone.0031721,PMC3280993,22359619,CC BY,"Highly pathogenic avian influenza viruses (HPAIVs) cause severe disease in humans. There are no effective vaccines or antiviral therapies currently available to control fatal outbreaks due in part to the lack of understanding of virus-mediated immunopathology. In our study, we used hemagglutinin (HA) of H5N1 virus to investigate the related signaling pathways and their relationship to dysregulated innate immune reaction. We found the HA of H5N1 avian influenza triggered an abnormal innate immune signalling in the pulmonary epithelial cells, through an unusual process involving activation of Janus kinase 3 (JAK3) that is exclusively associated with γc chain and is essential for signaling via all γc cytokine receptors. By using a selective JAK3 inhibitor and JAK3 knockout mice, we have, for the first time, demonstrated the ability to target active JAK3 to counteract injury to the lungs and protect immunocytes from acute hypercytokinemia -induced destruction following the challenge of H5N1 HA in vitro and in vivo. On the basis of the present data, it appears that the efficacy of selective JAK3 inhibition is likely based on its ability to block multiple cytokines and protect against a superinflammatory response to pathogen-associated molecular patterns (PAMPs) attack. Our findings highlight the potential value of selective JAK3 inhibitor in treating the fatal immunopathology caused by H5N1 challenge.",2012 Feb 16,"['Xu, Wei', 'Chen, Minhui', 'Ge, Nanhai', 'Xu, Jun']",PLoS One,,,True
98086d212b4a5249cfc45f05953fd0abf43891d9,PMC,Trends in Notifiable Infectious Diseases in China: Implications for Surveillance and Population Health Policy,http://dx.doi.org/10.1371/journal.pone.0031076,PMC3281048,22359565,CC BY,"This study aimed to analyse trends in notifiable infectious diseases in China, in their historical context. Both English and Chinese literature was searched and diseases were categorised according to the type of disease or transmission route. Temporal trends of morbidity and mortality rates were calculated for eight major infectious diseases types. Strong government commitment to public health responses and improvements in quality of life has led to the eradication or containment of a wide range of infectious diseases in China. The overall infectious diseases burden experienced a dramatic drop during 1975–1995, but since then, it reverted and maintained a gradual upward trend to date. Most notifiable diseases are contained at a low endemic level; however, local small-scale outbreaks remain common. Tuberculosis, as a bacterial infection, has re-emerged since the 1990s and has become prevalent in the country. Sexually transmitted infections are in a rapid, exponential growth phase, spreading from core groups to the general population. Together human immunodeficiency virus (HIV), they account for 39% of all death cases due to infectious diseases in China in 2008. Zoonotic infections, such as severe acute respiratory syndrome (SARS), rabies and influenza, pose constant threats to Chinese residents and remain the most deadly disease type among the infected individuals. Therefore, second-generation surveillance of behavioural risks or vectors associated with pathogen transmission should be scaled up. It is necessary to implement public health interventions that target HIV and relevant coinfections, address transmission associated with highly mobile populations, and reduce the risk of cross-species transmission of zoonotic pathogens.",2012 Feb 16,"['Zhang, Lei', 'Wilson, David P.']",PLoS One,,,True
e725656b0cdd0f7e78279187e0c251cf8683f1e5,PMC,Removal of Hepatitis C Virus-Infected Cells by a Zymogenized Bacterial Toxin,http://dx.doi.org/10.1371/journal.pone.0032320,PMC3281143,22359682,CC BY,"Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and has become a global health threat. No HCV vaccine is currently available and treatment with antiviral therapy is associated with adverse side effects. Moreover, there is no preventive therapy for recurrent hepatitis C post liver transplantation. The NS3 serine protease is necessary for HCV replication and represents a prime target for developing anti HCV therapies. Recently we described a therapeutic approach for eradication of HCV infected cells that is based on protein delivery of two NS3 protease-activatable recombinant toxins we named “zymoxins”. These toxins were inactivated by fusion to rationally designed inhibitory peptides via NS3-cleavable linkers. Once delivered to cells where NS3 protease is present, the inhibitory peptide is removed resulting in re-activation of cytotoxic activity. The zymoxins we described suffered from two limitations: they required high levels of protease for activation and had basal activities in the un-activated form that resulted in a narrow potential therapeutic window. Here, we present a solution that overcame the major limitations of the “first generation zymoxins” by converting MazF ribonuclease, the toxic component of the E. coli chromosomal MazEF toxin-antitoxin system, into an NS3-activated zymoxin that is introduced to cells by means of gene delivery. We constructed an expression cassette that encodes for a single polypeptide that incorporates both the toxin and a fragment of its potent natural antidote, MazE, linked via an NS3-cleavable linker. While covalently paired to its inhibitor, the ribonuclease is well tolerated when expressed in naïve, healthy cells. In contrast, activating proteolysis that is induced by even low levels of NS3, results in an eradication of NS3 expressing model cells and HCV infected cells. Zymoxins may thus become a valuable tool in eradicating cells infected by intracellular pathogens that express intracellular proteases.",2012 Feb 16,"['Shapira, Assaf', 'Shapira, Shiran', 'Gal-Tanamy, Meital', 'Zemel, Romy', 'Tur-Kaspa, Ran', 'Benhar, Itai']",PLoS One,,,True
5b87c5054e29782b51940d6ab29ce3ca2b27d54b,PMC,Transmission of Infectious Diseases En Route to Habitat Hotspots,http://dx.doi.org/10.1371/journal.pone.0031290,PMC3282722,22363606,CC BY,"BACKGROUND: The spread of infectious diseases in wildlife populations is influenced by patterns of between-host contacts. Habitat “hotspots” - places attracting a large numbers of individuals or social groups - can significantly alter contact patterns and, hence, disease propagation. Research on the importance of habitat hotspots in wildlife epidemiology has primarily focused on how inter-individual contacts occurring at the hotspot itself increase disease transmission. However, in territorial animals, epidemiologically important contacts may primarily occur as animals cross through territories of conspecifics en route to habitat hotspots. So far, the phenomenon has received little attention. Here, we investigate the importance of these contacts in the case where infectious individuals keep visiting the hotspots and in the case where these individuals are not able to travel to the hotspot any more. METHODOLOGY AND PRINCIPAL FINDINGS: We developed a simulation epidemiological model to investigate both cases in a scenario when transmission at the hotspot does not occur. We find that (i) hotspots still exacerbate epidemics, (ii) when infectious individuals do not travel to the hotspot, the most vulnerable individuals are those residing at intermediate distances from the hotspot rather than nearby, and (iii) the epidemiological vulnerability of a population is the highest when the number of hotspots is intermediate. CONCLUSIONS AND SIGNIFICANCE: By altering animal movements in their vicinity, habitat hotspots can thus strongly increase the spread of infectious diseases, even when disease transmission does not occur at the hotspot itself. Interestingly, when animals only visit the nearest hotspot, creating additional artificial hotspots, rather than reducing their number, may be an efficient disease control measure.",2012 Feb 20,"['Benavides, Julio', 'Walsh, Peter D.', 'Meyers, Lauren Ancel', 'Raymond, Michel', 'Caillaud, Damien']",PLoS One,,,True
7e889eb3dc54b352c2689b84be7a52f121f80b56,PMC,The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members,http://dx.doi.org/10.1371/journal.pone.0031961,PMC3282796,22363774,CC BY,"The Interferon induced transmembrane proteins (IFITM) are a family of transmembrane proteins that is known to inhibit cell invasion of viruses such as HIV-1 and influenza. We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure. We mined the Dispanins in 36 eukaryotic species, covering all major eukaryotic groups, and investigated their evolutionary history using Bayesian and maximum likelihood approaches to infer a phylogenetic tree. We identified ten human genes that together with the known IFITM genes form the Dispanin family. We show that the Dispanins first emerged in eukaryotes in a common ancestor of choanoflagellates and metazoa, and that the family later expanded in vertebrates where it forms four subfamilies (A–D). Interestingly, we also find that the family is found in several different phyla of bacteria and propose that it was horizontally transferred to eukaryotes from bacteria in the common ancestor of choanoflagellates and metazoa. The bacterial and eukaryotic sequences have a considerably conserved protein structure. In conclusion, we introduce a novel family, the Dispanins, together with a nomenclature based on the evolutionary origin.",2012 Feb 20,"['Sällman Almén, Markus', 'Bringeland, Nathalie', 'Fredriksson, Robert', 'Schiöth, Helgi B.']",PLoS One,,,True
4e9f9684ec67208f02fa5b822b18ccfa79ca6b6b,PMC,"First Human Rabies Case in French Guiana, 2008: Epidemiological Investigation and Control",http://dx.doi.org/10.1371/journal.pntd.0001537,PMC3283561,22363830,CC BY,"BACKGROUND: Until 2008, human rabies had never been reported in French Guiana. On 28 May 2008, the French National Reference Center for Rabies (Institut Pasteur, Paris) confirmed the rabies diagnosis, based on hemi-nested polymerase chain reaction on skin biopsy and saliva specimens from a Guianan, who had never travelled overseas and died in Cayenne after presenting clinically typical meningoencephalitis. METHODOLOGY/PRINCIPAL FINDINGS: Molecular typing of the virus identified a Lyssavirus (Rabies virus species), closely related to those circulating in hematophagous bats (mainly Desmodus rotundus) in Latin America. A multidisciplinary Crisis Unit was activated. Its objectives were to implement an epidemiological investigation and a veterinary survey, to provide control measures and establish a communications program. The origin of the contamination was not formally established, but was probably linked to a bat bite based on the virus type isolated. After confirming exposure of 90 persons, they were vaccinated against rabies: 42 from the case's entourage and 48 healthcare workers. To handle that emergence and the local population's increased demand to be vaccinated, a specific communications program was established using several media: television, newspaper, radio. CONCLUSION/SIGNIFICANCE: This episode, occurring in the context of a Department far from continental France, strongly affected the local population, healthcare workers and authorities, and the management team faced intense pressure. This observation confirms that the risk of contracting rabies in French Guiana is real, with consequences for population educational program, control measures, medical diagnosis and post-exposure prophylaxis.",2012 Feb 21,"['Meynard, Jean-Baptiste', 'Flamand, Claude', 'Dupuy, Céline', 'Mahamat, Aba', 'Eltges, Françoise', 'Queuche, Frederic', 'Renner, Julien', 'Fontanella, Jean-Michel', 'Hommel, Didier', 'Dussart, Philippe', 'Grangier, Claire', 'Djossou, Félix', 'Dacheux, Laurent', 'Goudal, Maryvonne', 'Berger, Franck', 'Ardillon, Vanessa', 'Krieger, Nicolas', 'Bourhy, Hervé', 'Spiegel, André']",PLoS Negl Trop Dis,,,True
889d6b9282d6ee49c9bdde84352fe9c251e6aae5,PMC,"First Human Rabies Case in French Guiana, 2008: Epidemiological Investigation and Control",http://dx.doi.org/10.1371/journal.pntd.0001537,PMC3283561,22363830,CC BY,"BACKGROUND: Until 2008, human rabies had never been reported in French Guiana. On 28 May 2008, the French National Reference Center for Rabies (Institut Pasteur, Paris) confirmed the rabies diagnosis, based on hemi-nested polymerase chain reaction on skin biopsy and saliva specimens from a Guianan, who had never travelled overseas and died in Cayenne after presenting clinically typical meningoencephalitis. METHODOLOGY/PRINCIPAL FINDINGS: Molecular typing of the virus identified a Lyssavirus (Rabies virus species), closely related to those circulating in hematophagous bats (mainly Desmodus rotundus) in Latin America. A multidisciplinary Crisis Unit was activated. Its objectives were to implement an epidemiological investigation and a veterinary survey, to provide control measures and establish a communications program. The origin of the contamination was not formally established, but was probably linked to a bat bite based on the virus type isolated. After confirming exposure of 90 persons, they were vaccinated against rabies: 42 from the case's entourage and 48 healthcare workers. To handle that emergence and the local population's increased demand to be vaccinated, a specific communications program was established using several media: television, newspaper, radio. CONCLUSION/SIGNIFICANCE: This episode, occurring in the context of a Department far from continental France, strongly affected the local population, healthcare workers and authorities, and the management team faced intense pressure. This observation confirms that the risk of contracting rabies in French Guiana is real, with consequences for population educational program, control measures, medical diagnosis and post-exposure prophylaxis.",2012 Feb 21,"['Meynard, Jean-Baptiste', 'Flamand, Claude', 'Dupuy, Céline', 'Mahamat, Aba', 'Eltges, Françoise', 'Queuche, Frederic', 'Renner, Julien', 'Fontanella, Jean-Michel', 'Hommel, Didier', 'Dussart, Philippe', 'Grangier, Claire', 'Djossou, Félix', 'Dacheux, Laurent', 'Goudal, Maryvonne', 'Berger, Franck', 'Ardillon, Vanessa', 'Krieger, Nicolas', 'Bourhy, Hervé', 'Spiegel, André']",PLoS Negl Trop Dis,,,False
491084a67c24a54bdafc66ed3f940274b49e80d9,PMC,"First Human Rabies Case in French Guiana, 2008: Epidemiological Investigation and Control",http://dx.doi.org/10.1371/journal.pntd.0001537,PMC3283561,22363830,CC BY,"BACKGROUND: Until 2008, human rabies had never been reported in French Guiana. On 28 May 2008, the French National Reference Center for Rabies (Institut Pasteur, Paris) confirmed the rabies diagnosis, based on hemi-nested polymerase chain reaction on skin biopsy and saliva specimens from a Guianan, who had never travelled overseas and died in Cayenne after presenting clinically typical meningoencephalitis. METHODOLOGY/PRINCIPAL FINDINGS: Molecular typing of the virus identified a Lyssavirus (Rabies virus species), closely related to those circulating in hematophagous bats (mainly Desmodus rotundus) in Latin America. A multidisciplinary Crisis Unit was activated. Its objectives were to implement an epidemiological investigation and a veterinary survey, to provide control measures and establish a communications program. The origin of the contamination was not formally established, but was probably linked to a bat bite based on the virus type isolated. After confirming exposure of 90 persons, they were vaccinated against rabies: 42 from the case's entourage and 48 healthcare workers. To handle that emergence and the local population's increased demand to be vaccinated, a specific communications program was established using several media: television, newspaper, radio. CONCLUSION/SIGNIFICANCE: This episode, occurring in the context of a Department far from continental France, strongly affected the local population, healthcare workers and authorities, and the management team faced intense pressure. This observation confirms that the risk of contracting rabies in French Guiana is real, with consequences for population educational program, control measures, medical diagnosis and post-exposure prophylaxis.",2012 Feb 21,"['Meynard, Jean-Baptiste', 'Flamand, Claude', 'Dupuy, Céline', 'Mahamat, Aba', 'Eltges, Françoise', 'Queuche, Frederic', 'Renner, Julien', 'Fontanella, Jean-Michel', 'Hommel, Didier', 'Dussart, Philippe', 'Grangier, Claire', 'Djossou, Félix', 'Dacheux, Laurent', 'Goudal, Maryvonne', 'Berger, Franck', 'Ardillon, Vanessa', 'Krieger, Nicolas', 'Bourhy, Hervé', 'Spiegel, André']",PLoS Negl Trop Dis,,,False
990fbc24eb6832897917d21d4d3d60919c7a822c,PMC,"First Human Rabies Case in French Guiana, 2008: Epidemiological Investigation and Control",http://dx.doi.org/10.1371/journal.pntd.0001537,PMC3283561,22363830,CC BY,"BACKGROUND: Until 2008, human rabies had never been reported in French Guiana. On 28 May 2008, the French National Reference Center for Rabies (Institut Pasteur, Paris) confirmed the rabies diagnosis, based on hemi-nested polymerase chain reaction on skin biopsy and saliva specimens from a Guianan, who had never travelled overseas and died in Cayenne after presenting clinically typical meningoencephalitis. METHODOLOGY/PRINCIPAL FINDINGS: Molecular typing of the virus identified a Lyssavirus (Rabies virus species), closely related to those circulating in hematophagous bats (mainly Desmodus rotundus) in Latin America. A multidisciplinary Crisis Unit was activated. Its objectives were to implement an epidemiological investigation and a veterinary survey, to provide control measures and establish a communications program. The origin of the contamination was not formally established, but was probably linked to a bat bite based on the virus type isolated. After confirming exposure of 90 persons, they were vaccinated against rabies: 42 from the case's entourage and 48 healthcare workers. To handle that emergence and the local population's increased demand to be vaccinated, a specific communications program was established using several media: television, newspaper, radio. CONCLUSION/SIGNIFICANCE: This episode, occurring in the context of a Department far from continental France, strongly affected the local population, healthcare workers and authorities, and the management team faced intense pressure. This observation confirms that the risk of contracting rabies in French Guiana is real, with consequences for population educational program, control measures, medical diagnosis and post-exposure prophylaxis.",2012 Feb 21,"['Meynard, Jean-Baptiste', 'Flamand, Claude', 'Dupuy, Céline', 'Mahamat, Aba', 'Eltges, Françoise', 'Queuche, Frederic', 'Renner, Julien', 'Fontanella, Jean-Michel', 'Hommel, Didier', 'Dussart, Philippe', 'Grangier, Claire', 'Djossou, Félix', 'Dacheux, Laurent', 'Goudal, Maryvonne', 'Berger, Franck', 'Ardillon, Vanessa', 'Krieger, Nicolas', 'Bourhy, Hervé', 'Spiegel, André']",PLoS Negl Trop Dis,,,False
1e6d38b98619d0d315d728291e97acde6c0012e1,PMC,Health System Resource Gaps and Associated Mortality from Pandemic Influenza across Six Asian Territories,http://dx.doi.org/10.1371/journal.pone.0031800,PMC3283680,22363739,CC BY,"BACKGROUND: Southeast Asia has been the focus of considerable investment in pandemic influenza preparedness. Given the wide variation in socio-economic conditions, health system capacity across the region is likely to impact to varying degrees on pandemic mitigation operations. We aimed to estimate and compare the resource gaps, and potential mortalities associated with those gaps, for responding to pandemic influenza within and between six territories in Asia. METHODS AND FINDINGS: We collected health system resource data from Cambodia, Indonesia (Jakarta and Bali), Lao PDR, Taiwan, Thailand and Vietnam. We applied a mathematical transmission model to simulate a “mild-to-moderate” pandemic influenza scenario to estimate resource needs, gaps, and attributable mortalities at province level within each territory. The results show that wide variations exist in resource capacities between and within the six territories, with substantial mortalities predicted as a result of resource gaps (referred to here as “avoidable” mortalities), particularly in poorer areas. Severe nationwide shortages of mechanical ventilators were estimated to be a major cause of avoidable mortalities in all territories except Taiwan. Other resources (oseltamivir, hospital beds and human resources) are inequitably distributed within countries. Estimates of resource gaps and avoidable mortalities were highly sensitive to model parameters defining the transmissibility and clinical severity of the pandemic scenario. However, geographic patterns observed within and across territories remained similar for the range of parameter values explored. CONCLUSIONS: The findings have important implications for where (both geographically and in terms of which resource types) investment is most needed, and the potential impact of resource mobilization for mitigating the disease burden of an influenza pandemic. Effective mobilization of resources across administrative boundaries could go some way towards minimizing avoidable deaths.",2012 Feb 21,"['Rudge, James W.', 'Hanvoravongchai, Piya', 'Krumkamp, Ralf', 'Chavez, Irwin', 'Adisasmito, Wiku', 'Ngoc Chau, Pham', 'Phommasak, Bounlay', 'Putthasri, Weerasak', 'Shih, Chin-Shui', 'Stein, Mart', 'Timen, Aura', 'Touch, Sok', 'Reintjes, Ralf', 'Coker, Richard', None]",PLoS One,,,True
05513da119ba8f48c1c468a8a40a591b731c4479,PMC,"The role of facemasks and hand hygiene in the prevention of influenza transmission in households: results from a cluster randomised trial; Berlin, Germany, 2009-2011",http://dx.doi.org/10.1186/1471-2334-12-26,PMC3285078,22280120,CC BY,"BACKGROUND: Previous controlled studies on the effect of non-pharmaceutical interventions (NPI) - namely the use of facemasks and intensified hand hygiene - in preventing household transmission of influenza have not produced definitive results. We aimed to investigate efficacy, acceptability, and tolerability of NPI in households with influenza index patients. METHODS: We conducted a cluster randomized controlled trial during the pandemic season 2009/10 and the ensuing influenza season 2010/11. We included households with an influenza positive index case in the absence of further respiratory illness within the preceding 14 days. Study arms were wearing a facemask and practicing intensified hand hygiene (MH group), wearing facemasks only (M group) and none of the two (control group). Main outcome measure was laboratory confirmed influenza infection in a household contact. We used daily questionnaires to examine adherence and tolerability of the interventions. RESULTS: We recruited 84 households (30 control, 26 M and 28 MH households) with 82, 69 and 67 household contacts, respectively. In 2009/10 all 41 index cases had a influenza A (H1N1) pdm09 infection, in 2010/11 24 had an A (H1N1) pdm09 and 20 had a B infection. The total secondary attack rate was 16% (35/218). In intention-to-treat analysis there was no statistically significant effect of the M and MH interventions on secondary infections. When analysing only households where intervention was implemented within 36 h after symptom onset of the index case, secondary infection in the pooled M and MH groups was significantly lower compared to the control group (adjusted odds ratio 0.16, 95% CI, 0.03-0.92). In a per-protocol analysis odds ratios were significantly reduced among participants of the M group (adjusted odds ratio, 0.30, 95% CI, 0.10-0.94). With the exception of MH index cases in 2010/11 adherence was good for adults and children, contacts and index cases. CONCLUSIONS: Results suggest that household transmission of influenza can be reduced by the use of NPI, such as facemasks and intensified hand hygiene, when implemented early and used diligently. Concerns about acceptability and tolerability of the interventions should not be a reason against their recommendation. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (Identifier NCT00833885).",2012 Jan 26,"['Suess, Thorsten', 'Remschmidt, Cornelius', 'Schink, Susanne B', 'Schweiger, Brunhilde', 'Nitsche, Andreas', 'Schroeder, Kati', 'Doellinger, Joerg', 'Milde, Jeanette', 'Haas, Walter', 'Koehler, Irina', 'Krause, Gérard', 'Buchholz, Udo']",BMC Infect Dis,,,True
b1d4318370f0bf32b2c6afded3ef07c1a37abe7a,PMC,First Dating of a Recombination Event in Mammalian Tick-Borne Flaviviruses,http://dx.doi.org/10.1371/journal.pone.0031981,PMC3285191,22384119,CC BY,"The mammalian tick-borne flavivirus group (MTBFG) contains viruses associated with important human and animal diseases such as encephalitis and hemorrhagic fever. In contrast to mosquito-borne flaviviruses where recombination events are frequent, the evolutionary dynamic within the MTBFG was believed to be essentially clonal. This assumption was challenged with the recent report of several homologous recombinations within the Tick-borne encephalitis virus (TBEV). We performed a thorough analysis of publicly available genomes in this group and found no compelling evidence for the previously identified recombinations. However, our results show for the first time that demonstrable recombination (i.e., with large statistical support and strong phylogenetic evidences) has occurred in the MTBFG, more specifically within the Louping ill virus lineage. Putative parents, recombinant strains and breakpoints were further tested for statistical significance using phylogenetic methods. We investigated the time of divergence between the recombinant and parental strains in a Bayesian framework. The recombination was estimated to have occurred during a window of 282 to 76 years before the present. By unravelling the temporal setting of the event, we adduce hypotheses about the ecological conditions that could account for the observed recombination.",2012 Feb 22,"['Bertrand, Yann', 'Töpel, Mats', 'Elväng, Annelie', 'Melik, Wessam', 'Johansson, Magnus']",PLoS One,,,True
28040123483f1f80ef9b612102f0b2083eac4ec4,PMC,Epstein-Barr Virus Stimulates Torque Teno Virus Replication: A Possible Relationship to Multiple Sclerosis,http://dx.doi.org/10.1371/journal.pone.0032160,PMC3285200,22384166,CC BY,"Viral infections have been implicated in the pathogenesis of multiple sclerosis. Epstein-Barr virus (EBV) has frequently been investigated as a possible candidate and torque teno virus (TTV) has also been discussed in this context. Nevertheless, mechanistic aspects remain unresolved. We report viral replication, as measured by genome amplification, as well as quantitative PCR of two TTV-HD14 isolates isolated from multiple sclerosis brain in a series of EBV-positive and -negative lymphoblastoid and Burkitt's lymphoma cell lines. Our results demonstrate the replication of both transfected TTV genomes up to day 21 post transfection in all the evaluated cell lines. Quantitative amplification indicates statistically significant enhanced TTV replication in the EBV-positive cell lines, including the EBV-converted BJAB line, in comparison to the EBV-negative Burkitt's lymphoma cell line BJAB. This suggests a helper effect of EBV infections in the replication of TTV. The present study provides information on a possible interaction of EBV and TTV in the etiology and progression of multiple sclerosis.",2012 Feb 22,"['Borkosky, Silvia S.', 'Whitley, Corinna', 'Kopp-Schneider, Annette', 'zur Hausen, Harald', 'deVilliers, Ethel-Michele']",PLoS One,,,True
ef7110a9022bac2e50c995b0f6b826ff071e48f8,PMC,Isothermal Amplification Using a Chemical Heating Device for Point-of-Care Detection of HIV-1,http://dx.doi.org/10.1371/journal.pone.0031432,PMC3285652,22384022,CC0,"BACKGROUND: To date, the use of traditional nucleic acid amplification tests (NAAT) for detection of HIV-1 DNA or RNA has been restricted to laboratory settings due to time, equipment, and technical expertise requirements. The availability of a rapid NAAT with applicability for resource-limited or point-of-care (POC) settings would fill a great need in HIV diagnostics, allowing for timely diagnosis or confirmation of infection status, as well as facilitating the diagnosis of acute infection, screening and evaluation of infants born to HIV-infected mothers. Isothermal amplification methods, such as reverse-transcription, loop-mediated isothermal amplification (RT-LAMP), exhibit characteristics that are ideal for POC settings, since they are typically quicker, easier to perform, and allow for integration into low-tech, portable heating devices. METHODOLOGY/SIGNIFICANT FINDINGS: In this study, we evaluated the HIV-1 RT-LAMP assay using portable, non-instrumented nucleic acid amplification (NINA) heating devices that generate heat from the exothermic reaction of calcium oxide and water. The NINA heating devices exhibited stable temperatures throughout the amplification reaction and consistent amplification results between three separate devices and a thermalcycler. The performance of the NINA heaters was validated using whole blood specimens from HIV-1 infected patients. CONCLUSION: The RT-LAMP isothermal amplification method used in conjunction with a chemical heating device provides a portable, rapid and robust NAAT platform that has the potential to facilitate HIV-1 testing in resource-limited settings and POC.",2012 Feb 23,"['Curtis, Kelly A.', 'Rudolph, Donna L.', 'Nejad, Irene', 'Singleton, Jered', 'Beddoe, Andy', 'Weigl, Bernhard', 'LaBarre, Paul', 'Owen, S. Michele']",PLoS One,,,True
d79628296e95343f9d5557983d7e19b66145b384,PMC,A rigorous approach to facilitate and guarantee the correctness of the genetic testing management in human genome information systems,http://dx.doi.org/10.1186/1471-2164-12-S4-S13,PMC3287582,22369688,CC BY,"BACKGROUND: Recent medical and biological technology advances have stimulated the development of new testing systems that have been providing huge, varied amounts of molecular and clinical data. Growing data volumes pose significant challenges for information processing systems in research centers. Additionally, the routines of genomics laboratory are typically characterized by high parallelism in testing and constant procedure changes. RESULTS: This paper describes a formal approach to address this challenge through the implementation of a genetic testing management system applied to human genome laboratory. We introduced the Human Genome Research Center Information System (CEGH) in Brazil, a system that is able to support constant changes in human genome testing and can provide patients updated results based on the most recent and validated genetic knowledge. Our approach uses a common repository for process planning to ensure reusability, specification, instantiation, monitoring, and execution of processes, which are defined using a relational database and rigorous control flow specifications based on process algebra (ACP). The main difference between our approach and related works is that we were able to join two important aspects: 1) process scalability achieved through relational database implementation, and 2) correctness of processes using process algebra. Furthermore, the software allows end users to define genetic testing without requiring any knowledge about business process notation or process algebra. CONCLUSIONS: This paper presents the CEGH information system that is a Laboratory Information Management System (LIMS) based on a formal framework to support genetic testing management for Mendelian disorder studies. We have proved the feasibility and showed usability benefits of a rigorous approach that is able to specify, validate, and perform genetic testing using easy end user interfaces.",2011 Dec 22,"['Araújo, Luciano V', 'Malkowski, Simon', 'Braghetto, Kelly R', 'Passos-Bueno, Maria R', 'Zatz, Mayana', 'Pu, Calton', 'Ferreira, João E']",BMC Genomics,,,True
1817050ed534376723c94abc3b5496beea55ed5b,PMC,Antimicrobial resistance and virulence factors in Escherichia coli from swedish dairy calves,http://dx.doi.org/10.1186/1751-0147-54-2,PMC3287958,22280887,CC BY,"BACKGROUND: In Sweden, knowledge about the role of enteropathogenic Escherichia coli in neonatal calf diarrhea and the occurrence of antimicrobial resistance in E. coli from young calves is largely unknown. This has therapeutic concern and such knowledge is also required for prudent use of antimicrobials. METHODS: In a case control study Esherichia coli isolated from faecal samples from dairy calves were phenotyped by biochemical fingerprinting and analyzed for virulence genes by PCR. Antimicrobial susceptibility was tested by determination of minimum inhibitory concentration (MIC). Farm management data were collected and Fisher's exact test and univariable and multivariable logistic regression analysis were performed. RESULTS: Of 95 E. coli tested for antimicrobial susceptibility 61% were resistant to one or more substances and 28% were multi-resistant. The virulence gene F5 (K99) was not found in any isolate. In total, 21 out of 40 of the investigated virulence genes were not detected or rarely detected. The virulence genes espP, irp, and fyuA were more common in resistant E. coli than in fully susceptible isolates (P < 0.05). The virulence gene terZ was associated with calf diarrhea (P ≤ 0.01). The participating 85 herds had a median herd size of 80 lactating cows. Herds with calf diarrhea problems were larger (> 55 cows; P < 0.001), had higher calf mortality (P ≤ 0.01) and calf group feeders were more in use (P < 0.05), compared to herds without calf diarrhea problems. There was no association between calf diarrhea and diversity of enteric E. coli. CONCLUSIONS: Antimicrobial resistance was common in E. coli from pre-weaned dairy calves, occurring particularly in calves from herds experiencing calf diarrhea problems. The results indicate that more factors than use of antimicrobials influence the epidemiology of resistant E. coli. Enteropathogenic E. coli seems to be an uncommon cause of neonatal calf diarrhea in Swedish dairy herds. In practice, calf diarrhea should be regarded holistically in a context of infectious agents, calf immunity, management practices etc. We therefore advice against routine antimicrobial treatment and recommend that bacteriological cultures, followed by testing for antimicrobial susceptibility and for virulence factors, are used to guide decisions on such treatment.",2012 Jan 26,"['de Verdier, Kerstin', 'Nyman, Ann', 'Greko, Christina', 'Bengtsson, Björn']",Acta Vet Scand,,,True
4cc4711e7794e52f303fdd8557dd175e71989c7b,PMC,Dectin-1 and DC-SIGN Polymorphisms Associated with Invasive Pulmonary Aspergillosis Infection,http://dx.doi.org/10.1371/journal.pone.0032273,PMC3288082,22384201,CC BY,"The recognition of pathogen-derived structures by C-type lectins and the chemotactic activity mediated by the CCL2/CCR2 axis are critical steps in determining the host immune response to fungi. The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA). Twenty-seven SNPs were selected using a hybrid functional/tagging approach and genotyped in 182 haematological patients, fifty-seven of them diagnosed with proven or probable IPA according to the 2008 EORTC/MSG criteria. Association analysis revealed that carriers of the Dectin-1 (rs3901533 T/T) and Dectin-1 (rs7309123 G/G) genotypes and DC-SIGN (rs4804800 G), DC-SIGN (rs11465384 T), DC-SIGN (7248637 A) and DC-SIGN (7252229 C) alleles had a significantly increased risk of IPA infection (OR = 5.59 95%CI 1.37–22.77; OR = 4.91 95%CI 1.52–15.89; OR = 2.75 95%CI 1.27–5.95; OR = 2.70 95%CI 1.24–5.90; OR = 2.39 95%CI 1.09–5.22 and OR = 2.05 95%CI 1.00–4.22, respectively). There was also a significantly increased frequency of galactomannan positivity among patients carrying the Dectin-1 (rs3901533_T) allele and Dectin-1 (rs7309123_G/G) genotype. In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1 (rs7309123) polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. SNP-SNP interaction (epistasis) analysis revealed significant interactions models including SNPs in Dectin-1, Dectin-2, CCL2 and CCR2 genes, with synergistic genetic effects. Although these results need to be further validated in larger cohorts, they suggest that Dectin-1, DC-SIGN, Dectin-2, CCL2 and CCR2 genetic variants influence the risk of IPA infection and might be useful in developing a risk-adapted prophylaxis.",2012 Feb 27,"['Sainz, Juan', 'Lupiáñez, Carmen Belén', 'Segura-Catena, Juana', 'Vazquez, Lourdes', 'Ríos, Rafael', 'Oyonarte, Salvador', 'Hemminki, Kari', 'Försti, Asta', 'Jurado, Manuel']",PLoS One,,,True
6f62efb20f820241aeb1a8e16af68502fedc9b43,PMC,GmPHD5 acts as an important regulator for crosstalk between histone H3K4 di-methylation and H3K14 acetylation in response to salinity stress in soybean,http://dx.doi.org/10.1186/1471-2229-11-178,PMC3288756,22168212,CC BY,"BACKGROUND: Accumulated evidence suggest that specific patterns of histone posttranslational modifications (PTMs) and their crosstalks may determine transcriptional outcomes. However, the regulatory mechanisms of these ""histone codes"" in plants remain largely unknown. RESULTS: In this study, we demonstrate for the first time that a salinity stress inducible PHD (plant homeodomain) finger domain containing protein GmPHD5 can read the ""histone code"" underlying the methylated H3K4. GmPHD5 interacts with other DNA binding proteins, including GmGNAT1 (an acetyl transferase), GmElongin A (a transcription elongation factor) and GmISWI (a chromatin remodeling protein). Our results suggest that GmPHD5 can recognize specific histone methylated H3K4, with preference to di-methylated H3K4. Here, we illustrate that the interaction between GmPHD5 and GmGNAT1 is regulated by the self-acetylation of GmGNAT1, which can also acetylate histone H3. GmGNAT1 exhibits a preference toward acetylated histone H3K14. These results suggest a histone crosstalk between methylated H3K4 and acetylated H3K14. Consistent to its putative roles in gene regulation under salinity stress, we showed that GmPHD5 can bind to the promoters of some confirmed salinity inducible genes in soybean. CONCLUSION: Here, we propose a model suggesting that the nuclear protein GmPHD5 is capable of regulating the crosstalk between histone methylation and histone acetylation of different lysine residues. Nevertheless, GmPHD5 could also recruit chromatin remodeling factors and transcription factors of salt stress inducible genes to regulate their expression in response to salinity stress.",2011 Dec 15,"['Wu, Tao', 'Pi, Er-Xu', 'Tsai, Sau-Na', 'Lam, Hon-Ming', 'Sun, Sai-Ming', 'Kwan, Yiu Wa', 'Ngai, Sai-Ming']",BMC Plant Biol,,,True
495132370917fdb1762cd47fa73e9e6ff94a60b6,PMC,Development and Characterization of a Reverse Genetic System for Studying Dengue Virus Serotype 3 Strain Variation and Neutralization,http://dx.doi.org/10.1371/journal.pntd.0001486,PMC3289595,22389731,CC BY,"Dengue viruses (DENV) are enveloped single-stranded positive-sense RNA viruses transmitted by Aedes spp. mosquitoes. There are four genetically distinct serotypes designated DENV-1 through DENV-4, each further subdivided into distinct genotypes. The dengue scientific community has long contended that infection with one serotype confers lifelong protection against subsequent infection with the same serotype, irrespective of virus genotype. However this hypothesis is under increased scrutiny and the role of DENV genotypic variation in protection from repeated infection is less certain. As dengue vaccine trials move increasingly into field-testing, there is an urgent need to develop tools to better define the role of genotypic variation in DENV infection and immunity. To better understand genotypic variation in DENV-3 neutralization and protection, we designed and constructed a panel of isogenic, recombinant DENV-3 infectious clones, each expressing an envelope glycoprotein from a different DENV-3 genotype; Philippines 1982 (genotype I), Thailand 1995 (genotype II), Sri Lanka 1989 and Cuba 2002 (genotype III) and Puerto Rico 1977 (genotype IV). We used the panel to explore how natural envelope variation influences DENV-polyclonal serum interactions. When the recombinant viruses were tested in neutralization assays using immune sera from primary DENV infections, neutralization titers varied by as much as ∼19-fold, depending on the expressed envelope glycoprotein. The observed variability in neutralization titers suggests that relatively few residue changes in the E glycoprotein may have significant effects on DENV specific humoral immunity and influence antibody mediated protection or disease enhancement in the setting of both natural infection and vaccination. These genotypic differences are also likely to be important in temporal and spatial microevolution of DENV-3 in the background of heterotypic neutralization. The recombinant and synthetic tools described here are valuable for testing hypotheses on genetic determinants of DENV-3 immunopathogenesis.",2012 Feb 28,"['Messer, William B.', 'Yount, Boyd', 'Hacker, Kari E.', 'Donaldson, Eric F.', 'Huynh, Jeremy P.', 'de Silva, Aravinda M.', 'Baric, Ralph S.']",PLoS Negl Trop Dis,,,True
f2615e2f1b1e1de90023706bf99405151406bbd8,PMC,Etiology and Clinical Characterization of Respiratory Virus Infections in Adult Patients Attending an Emergency Department in Beijing,http://dx.doi.org/10.1371/journal.pone.0032174,PMC3289638,22389685,CC BY,"BACKGROUND: Acute respiratory tract infections (ARTIs) represent a serious global health burden. To date, few reports have addressed the prevalence of respiratory viruses (RVs) in adults with ARTIs attending an emergency department (ED). Therefore, the potential impact of respiratory virus infections on such patients remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: To determine the epidemiological and clinical profiles of common and recently discovered respiratory viruses in adults with ARTIs attending an ED in Beijing, a 1-year consecutive study was conducted from May, 2010, to April, 2011. Nose and throat swab samples from 416 ARTI patients were checked for 13 respiratory viruses using multiple reverse transcription polymerase chain reaction(RT-PCR) assays for common respiratory viruses, including influenza viruses (Flu) A, B, and adenoviruses (ADVs), picornaviruses (PICs), respiratory syncytial virus (RSV), parainfluenza viruses (PIVs) 1–3, combined with real-time RT-PCR for human metapneumovirus (HMPV) and human coronaviruses (HCoVs, -OC43, -229E, -NL63, and -HKU1). Viral pathogens were detected in 52.88% (220/416) of patient samples, and 7.21% (30/416) of patients tested positive for more than one virus. PICs (17.79%) were the dominant agents detected, followed by FluA (16.11%), HCoVs (11.78%), and ADV (11.30%). HMPV, PIVs, and FluB were also detected (<3%), but not RSV. The total prevalence and the dominant virus infections detected differed significantly between ours and a previous report. Co-infection rates were high for HCoV-229E (12/39, 30.76%), PIC (22/74, 29.73%), ADV (12/47, 25.53%) and FluA (15/67, 22.39%). Different patterns of clinical symptoms were associated with different respiratory viruses. CONCLUSIONS: The pattern of RV involvement in adults with ARTIs attending an ED in China differs from that previously reported. The high prevalence of viruses (PIC, FluA, HCoVs and ADV) reported here strongly highlight the need for the development of safe and effective therapeutic approaches for these viruses.",2012 Feb 28,"['Yu, Xiaoyan', 'Lu, Roujian', 'Wang, Zhong', 'Zhu, Na', 'Wang, Wen', 'Julian, Druce', 'Chris, Birch', 'Lv, Jianxin', 'Tan, Wenjie']",PLoS One,,,True
6ea1978890ab099e90e61ddf078b6d983e60b07f,PMC,Repertoire of Intensive Care Unit Pneumonia Microbiota,http://dx.doi.org/10.1371/journal.pone.0032486,PMC3289664,22389704,CC BY,"Despite the considerable number of studies reported to date, the causative agents of pneumonia are not completely identified. We comprehensively applied modern and traditional laboratory diagnostic techniques to identify microbiota in patients who were admitted to or developed pneumonia in intensive care units (ICUs). During a three-year period, we tested the bronchoalveolar lavage (BAL) of patients with ventilator-associated pneumonia, community-acquired pneumonia, non-ventilator ICU pneumonia and aspiration pneumonia, and compared the results with those from patients without pneumonia (controls). Samples were tested by amplification of 16S rDNA, 18S rDNA genes followed by cloning and sequencing and by PCR to target specific pathogens. We also included culture, amoeba co-culture, detection of antibodies to selected agents and urinary antigen tests. Based on molecular testing, we identified a wide repertoire of 160 bacterial species of which 73 have not been previously reported in pneumonia. Moreover, we found 37 putative new bacterial phylotypes with a 16S rDNA gene divergence ≥98% from known phylotypes. We also identified 24 fungal species of which 6 have not been previously reported in pneumonia and 7 viruses. Patients can present up to 16 different microorganisms in a single BAL (mean ± SD; 3.77±2.93). Some pathogens considered to be typical for ICU pneumonia such as Pseudomonas aeruginosa and Streptococcus species can be detected as commonly in controls as in pneumonia patients which strikingly highlights the existence of a core pulmonary microbiota. Differences in the microbiota of different forms of pneumonia were documented.",2012 Feb 28,"['Bousbia, Sabri', 'Papazian, Laurent', 'Saux, Pierre', 'Forel, Jean Marie', 'Auffray, Jean-Pierre', 'Martin, Claude', 'Raoult, Didier', 'La Scola, Bernard']",PLoS One,,,True
a086b50101fcfa29f699b41cbf034ae71ac70bff,PMC,Discovery and Genomic Characterization of Noroviruses from a Gastroenteritis Outbreak in Domestic Cats in the US,http://dx.doi.org/10.1371/journal.pone.0032739,PMC3289677,22389721,CC BY,"Norovirus (NoV) RNA was detected in the stools of 6 out 14 (42.8%) 8–12-week-old cats with enteritis from a feline shelter, in New York State. Upon sequence analysis of the complete capsid, the six NoVs were found to be identical, suggesting the spread of a unique NoV strain in the shelter. The full-length genomic sequence (7839 nt) of one feline NoV, CU081210E/2010/US, was determined. In the capsid protein VP1 region, the virus displayed the highest amino acid identity to animal genogroup IV genotype 2 (GIV.2) NoVs: lion/Pistoia-387/06/IT (97.9%) and dog/Bari-170/07/IT (90.4%). These findings document the discovery of a novel feline calicivirus, different from vesiviruses, and extend the spectrum of NoV host range. Epidemiological studies using feline NoV-specific diagnostic tools and experimental infection of cats are required to understand whether NoVs have a pathogenic role in this species.",2012 Feb 28,"['Pinto, Pierfrancesco', 'Wang, Qiuhong', 'Chen, Ning', 'Dubovi, Edward J.', 'Daniels, Joshua B.', 'Millward, Laurie M.', 'Buonavoglia, Canio', 'Martella, Vito', 'Saif, Linda J.']",PLoS One,,,True
fff1e7b356f0d6cf7b28b019974833200e38f843,PMC,Clinical Manifestations Vary with Different Age Spectrums in Infants with Kawasaki Disease,http://dx.doi.org/10.1100/2012/210382,PMC3289979,22454602,CC BY,"Background. Kawasaki disease (KD) is an acute systemic vasculitis with unknown etiology. The diagnosis of KD depends on clinical manifestations. The prevalence of coronary artery abnormality (CAA) is 11.0% and results in cardiac sequelae, such as myocardial infarction or coronary aneurysm, which are the most serious complications in KD. Methods. We divided KD's children into different age groups: ≤6 months old, 7 months to 1 year old, and >1 year old, respectively. Different parameters were compared in each group. Results. Infants ≤6 months old are less likely to fulfill KD's major diagnostic criteria within 10 days, are prone to develop incomplete KD with the lowest cholesterol level, and have the greatest chance to have CAA and the laboratory features associated with CAA, such as the longest time needed to confirm CA diagnosis, lower hemoglobin level, lower albumin level, and higher platelet count. Infants <1 year old develop higher percentage of leukocytosis and sterile pyuria. But this group has fewer patients with neck lymphadenopathy.",2012 Feb 15,"['Liu, Hao-Chuan', 'Lo, Chiao-Wei', 'Hwang, Betau', 'Lee, Pi-Chang']",ScientificWorldJournal,,,True
86e3f31b72109395a9dd02071bf83aeb7fa6803c,PMC,Lethal Nipah Virus Infection Induces Rapid Overexpression of CXCL10,http://dx.doi.org/10.1371/journal.pone.0032157,PMC3290546,22393386,CC BY,"Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10), an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.",2012 Feb 29,"['Mathieu, Cyrille', 'Guillaume, Vanessa', 'Sabine, Amélie', 'Ong, Kien Chai', 'Wong, Kum Thong', 'Legras-Lachuer, Catherine', 'Horvat, Branka']",PLoS One,,,True
5881e62ed1be0eec6603b49cf10c413d3c1e560f,PMC,Influenza Virus Respiratory Infection and Transmission Following Ocular Inoculation in Ferrets,http://dx.doi.org/10.1371/journal.ppat.1002569,PMC3291616,22396651,CC0,"While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. The ocular surface represents both a potential site of virus replication and a portal of entry for establishment of a respiratory infection. However, the properties which govern ocular tropism of influenza viruses, the mechanisms of virus spread from ocular to respiratory tissue, and the potential differences in respiratory disease initiated from different exposure routes are poorly understood. Here, we established a ferret model of ocular inoculation to explore the development of virus pathogenicity and transmissibility following influenza virus exposure by the ocular route. We found that multiple subtypes of human and avian influenza viruses mounted a productive virus infection in the upper respiratory tract of ferrets following ocular inoculation, and were additionally detected in ocular tissue during the acute phase of infection. H5N1 viruses maintained their ability for systemic spread and lethal infection following inoculation by the ocular route. Replication-independent deposition of virus inoculum from ocular to respiratory tissue was limited to the nares and upper trachea, unlike traditional intranasal inoculation which results in virus deposition in both upper and lower respiratory tract tissues. Despite high titers of replicating transmissible seasonal viruses in the upper respiratory tract of ferrets inoculated by the ocular route, virus transmissibility to naïve contacts by respiratory droplets was reduced following ocular inoculation. These data improve our understanding of the mechanisms of virus spread following ocular exposure and highlight differences in the establishment of respiratory disease and virus transmissibility following use of different inoculation volumes and routes.",2012 Mar 1,"['Belser, Jessica A.', 'Gustin, Kortney M.', 'Maines, Taronna R.', 'Pantin-Jackwood, Mary J.', 'Katz, Jacqueline M.', 'Tumpey, Terrence M.']",PLoS Pathog,,,True
3ba2641160cb0acdca16991443017f11d2d848c2,PMC,Critical Role of Perforin-dependent CD8+ T Cell Immunity for Rapid Protective Vaccination in a Murine Model for Human Smallpox,http://dx.doi.org/10.1371/journal.ppat.1002557,PMC3291617,22396645,CC BY,"Vaccination is highly effective in preventing various infectious diseases, whereas the constant threat of new emerging pathogens necessitates the development of innovative vaccination principles that also confer rapid protection in a case of emergency. Although increasing evidence points to T cell immunity playing a critical role in vaccination against viral diseases, vaccine efficacy is mostly associated with the induction of antibody responses. Here we analyze the immunological mechanism(s) of rapidly protective vaccinia virus immunization using mousepox as surrogate model for human smallpox. We found that fast protection against lethal systemic poxvirus disease solely depended on CD4 and CD8 T cell responses induced by vaccination with highly attenuated modified vaccinia virus Ankara (MVA) or conventional vaccinia virus. Of note, CD4 T cells were critically required to allow for MVA induced CD8 T cell expansion and perforin-mediated cytotoxicity was a key mechanism of MVA induced protection. In contrast, selected components of the innate immune system and B cell-mediated responses were fully dispensable for prevention of fatal disease by immunization given two days before challenge. In conclusion, our data clearly demonstrate that perforin-dependent CD8 T cell immunity plays a key role in MVA conferred short term protection against lethal mousepox. Rapid induction of T cell immunity might serve as a new paradigm for treatments that need to fit into a scenario of protective emergency vaccination.",2012 Mar 1,"['Kremer, Melanie', 'Suezer, Yasemin', 'Volz, Asisa', 'Frenz, Theresa', 'Majzoub, Monir', 'Hanschmann, Kay-Martin', 'Lehmann, Michael H.', 'Kalinke, Ulrich', 'Sutter, Gerd']",PLoS Pathog,,,True
3e035bd3c87d15ec4bca05cd13551c70d1bc5e78,PMC,Placement of Leucine Zipper Motifs at the Carboxyl Terminus of HIV-1 Protease Significantly Reduces Virion Production,http://dx.doi.org/10.1371/journal.pone.0032845,PMC3291649,22396796,CC BY,"Natural HIV-1 protease (PR) is homodimeric. Some researchers believe that interactions between HIV-1 Gag-Pol molecules trigger the activation of embedded PR (which mediates Gag and Gag-Pol cleavage), and that Gag-Pol assembly domains outside of PR may contribute to PR activation by influencing PR dimer interaction in a Gag-Pol context. To determine if the enhancement of PR dimer interaction facilitates PR activation, we placed single or tandem repeat leucine zippers (LZ) at the PR C-terminus, and looked for a correlation between enhanced Gag processing efficiency and increased Gag-PR-LZ multimerization capacity. We found significant reductions in virus-like particles (VLPs) produced by HIV-1 mutants, with LZ fused to the end of PR as a result of enhanced Gag cleavage efficiency. Since VLP production can be restored to wt levels following PR activity inhibition, this assembly defect is considered PR activity-dependent. We also found a correlation between the LZ enhancement effect on Gag cleavage and enhanced Gag-PR multimerization. The results suggest that PR dimer interactions facilitated by forced Gag-PR multimerization lead to premature Gag cleavage, likely a result of premature PR activation. Our conclusion is that placement of a heterologous dimerization domain downstream of PR enhances PR-mediated Gag cleavage efficiency, implying that structural conformation, rather than the primary sequence outside of PR, is a major determinant of HIV-1 PR activation.",2012 Mar 1,"['Pan, Yen-Yu', 'Wang, Shiu-Mei', 'Huang, Kuo-Jung', 'Chiang, Chien-Cheng', 'Wang, Chin-Tien']",PLoS One,,,True
650c105dc3718ea36a7abffa0de7f9068390045f,PMC,A20 (Tnfaip3) Deficiency in Myeloid Cells Protects against Influenza A Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1002570,PMC3291650,22396652,CC BY,"The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. Influenza A virus (IAV) produces double-stranded RNA as an intermediate during the replication life cycle, which activates the intracellular pathogen recognition receptor RIG-I and induces the production of proinflammatory cytokines and antiviral interferon. Understanding the mechanisms that regulate innate immune responses to IAV and other viruses is of key importance to develop novel therapeutic strategies. Here we used myeloid cell specific A20 knockout mice to examine the role of the ubiquitin-editing protein A20 in the response of myeloid cells to IAV infection. A20 deficient macrophages were hyperresponsive to double stranded RNA and IAV infection, as illustrated by enhanced NF-κB and IRF3 activation, concomitant with increased production of proinflammatory cytokines, chemokines and type I interferon. In vivo this was associated with an increased number of alveolar macrophages and neutrophils in the lungs of IAV infected mice. Surprisingly, myeloid cell specific A20 knockout mice are protected against lethal IAV infection. These results challenge the general belief that an excessive host proinflammatory response is associated with IAV-induced lethality, and suggest that under certain conditions inhibition of A20 might be of interest in the management of IAV infections.",2012 Mar 1,"['Maelfait, Jonathan', 'Roose, Kenny', 'Bogaert, Pieter', 'Sze, Mozes', 'Saelens, Xavier', 'Pasparakis, Manolis', 'Carpentier, Isabelle', 'van Loo, Geert', 'Beyaert, Rudi']",PLoS Pathog,,,True
953e146785a16b34f944a8dacec8816d0df49e0c,PMC,"Antibody-Based Sensors: Principles, Problems and Potential for Detection of Pathogens and Associated Toxins",http://dx.doi.org/10.3390/s90604407,PMC3291918,22408533,CC BY,"Antibody-based sensors permit the rapid and sensitive analysis of a range of pathogens and associated toxins. A critical assessment of the implementation of such formats is provided, with reference to their principles, problems and potential for ‘on-site’ analysis. Particular emphasis is placed on the detection of foodborne bacterial pathogens, such as Escherichia coli and Listeria monocytogenes, and additional examples relating to the monitoring of fungal pathogens, viruses, mycotoxins, marine toxins and parasites are also provided.",2009 Jun 5,"['Byrne, Barry', 'Stack, Edwina', 'Gilmartin, Niamh', ""O'Kennedy, Richard""]",Sensors (Basel),,,True
058c0fc94ded8fa4e7a302081c3ea738d16a4b1a,PMC,Using Support Vector Machine and Evolutionary Profiles to Predict Antifreeze Protein Sequences,http://dx.doi.org/10.3390/ijms13022196,PMC3292016,22408447,CC BY,"Antifreeze proteins (AFPs) are ice-binding proteins. Accurate identification of new AFPs is important in understanding ice-protein interactions and creating novel ice-binding domains in other proteins. In this paper, an accurate method, called AFP_PSSM, has been developed for predicting antifreeze proteins using a support vector machine (SVM) and position specific scoring matrix (PSSM) profiles. This is the first study in which evolutionary information in the form of PSSM profiles has been successfully used for predicting antifreeze proteins. Tested by 10-fold cross validation and independent test, the accuracy of the proposed method reaches 82.67% for the training dataset and 93.01% for the testing dataset, respectively. These results indicate that our predictor is a useful tool for predicting antifreeze proteins. A web server (AFP_PSSM) that implements the proposed predictor is freely available.",2012 Feb 17,"['Zhao, Xiaowei', 'Ma, Zhiqiang', 'Yin, Minghao']",Int J Mol Sci,,,True
a3a0db5c445f85527672a6402d35269c06ce8f6b,PMC,Using Support Vector Machine and Evolutionary Profiles to Predict Antifreeze Protein Sequences,http://dx.doi.org/10.3390/ijms13022196,PMC3292016,22408447,CC BY,"Antifreeze proteins (AFPs) are ice-binding proteins. Accurate identification of new AFPs is important in understanding ice-protein interactions and creating novel ice-binding domains in other proteins. In this paper, an accurate method, called AFP_PSSM, has been developed for predicting antifreeze proteins using a support vector machine (SVM) and position specific scoring matrix (PSSM) profiles. This is the first study in which evolutionary information in the form of PSSM profiles has been successfully used for predicting antifreeze proteins. Tested by 10-fold cross validation and independent test, the accuracy of the proposed method reaches 82.67% for the training dataset and 93.01% for the testing dataset, respectively. These results indicate that our predictor is a useful tool for predicting antifreeze proteins. A web server (AFP_PSSM) that implements the proposed predictor is freely available.",2012 Feb 17,"['Zhao, Xiaowei', 'Ma, Zhiqiang', 'Yin, Minghao']",Int J Mol Sci,,,False
cfdac27f152143ecfce91f501ea6a992be428333,PMC,Reliability and External Validity of AMSTAR in Assessing Quality of TCM Systematic Reviews,http://dx.doi.org/10.1155/2012/732195,PMC3292204,22454679,CC BY,"Objective. The aim of this study is to measure the reliability and external validity of AMSTAR by applying it to a sample of TCM systematic reviews. Study Design and Methods. We tested the agreement, reliability, construct validity, and feasibility of AMSTAR through comparisons with OQAQ. Statistical analyses were performed by using SPSS 13.0. Results. A random of sample with 41 TCM systematic reviews was selected from a database. The interrater agreement of the individual items of AMSTAR was moderate with a mean kappa of 0.50 (95% CI: 0.26, 0.73). The ICC for AMSTAR against OQAQ (total score of 9 items, excluding item 10) was 0.87 (95% CI: 0.76, 0.93). Conclusions. Although there is room for improvement on few items, the new tool is reliable, valid, and easy to use for methodological quality assessment of systematic reviews on TCM.",2012 Feb 16,"['Kang, Deying', 'Wu, Yuxia', 'Hu, Dan', 'Hong, Qi', 'Wang, Jialiang', 'Zhang, Xin']",Evid Based Complement Alternat Med,,,True
03e9a22249dd6e201e347bb87cf96a931120f5c5,PMC,Rapid Screening for Entry Inhibitors of Highly Pathogenic Viruses under Low-Level Biocontainment,http://dx.doi.org/10.1371/journal.pone.0030538,PMC3292545,22396728,CC BY,"Emerging viruses including Nipah, Hendra, Lujo, and Junin viruses have enormous potential to spread rapidly. Nipah virus, after emerging as a zoonosis, has also evolved the capacity for human-to-human transmission. Most of the diseases caused by these pathogens are untreatable and require high biocontainment conditions. Universal methods for rapidly identifying and screening candidate antivirals are urgently needed. We have developed a modular antiviral platform strategy that relies on simple bioinformatic and genetic information about each pathogen. Central to this platform is the use of envelope glycoprotein cDNAs to establish multi-cycle replication systems under BSL2 conditions for viral pathogens that normally require BSL3 and BSL4 facilities. We generated monoclonal antibodies against Nipah G by cDNA immunization in rats, and we showed that these antibodies neutralize both Nipah and Hendra live viruses. We then used these effective Henipavirus inhibitors to validate our screening strategy. Our proposed strategy should contribute to the response capability for emerging infectious diseases, providing a way to initiate antiviral development immediately upon identifying novel viruses.",2012 Mar 2,"['Talekar, Aparna', 'Pessi, Antonello', 'Glickman, Fraser', 'Sengupta, Uttara', 'Briese, Thomas', 'Whitt, Michael A.', 'Mathieu, Cyrille', 'Horvat, Branka', 'Moscona, Anne', 'Porotto, Matteo']",PLoS One,,,True
3ed4b5616c342d7185015a8553a8f8350511ca21,PMC,Infection control management of patients with suspected highly infectious diseases in emergency departments: data from a survey in 41 facilities in 14 European countries,http://dx.doi.org/10.1186/1471-2334-12-27,PMC3292988,22284435,CC BY,"BACKGROUND: In Emergency and Medical Admission Departments (EDs and MADs), prompt recognition and appropriate infection control management of patients with Highly Infectious Diseases (HIDs, e.g. Viral Hemorrhagic Fevers and SARS) are fundamental for avoiding nosocomial outbreaks. METHODS: The EuroNHID (European Network for Highly Infectious Diseases) project collected data from 41 EDs and MADs in 14 European countries, located in the same facility as a national/regional referral centre for HIDs, using specifically developed checklists, during on-site visits from February to November 2009. RESULTS: Isolation rooms were available in 34 facilities (82,9%): these rooms had anteroom in 19, dedicated entrance in 15, negative pressure in 17, and HEPA filtration of exhausting air in 12. Only 6 centres (14,6%) had isolation rooms with all characteristics. Personnel trained for the recognition of HIDs was available in 24 facilities; management protocols for HIDs were available in 35. CONCLUSIONS: Preparedness level for the safe and appropriate management of HIDs is partially adequate in the surveyed EDs and MADs.",2012 Jan 28,"['Fusco, Francesco M', 'Schilling, Stefan', 'De Iaco, Giuseppina', 'Brodt, Hans-Reinhard', 'Brouqui, Philippe', 'Maltezou, Helena C', 'Bannister, Barbara', 'Gottschalk, René', 'Thomson, Gail', 'Puro, Vincenzo', 'Ippolito, Giuseppe', None]",BMC Infect Dis,,,True
c5078be94c34f8a7357c2b4a9e5ea3c19ecb45e2,PMC,"Use of Sensitive, Broad-Spectrum Molecular Assays and Human Airway Epithelium Cultures for Detection of Respiratory Pathogens",http://dx.doi.org/10.1371/journal.pone.0032582,PMC3293820,22403676,CC BY,"Rapid and accurate detection and identification of viruses causing respiratory tract infections is important for patient care and disease control. Despite the fact that several assays are available, identification of an etiological agent is not possible in ∼30% of patients suffering from respiratory tract diseases. Therefore, the aim of the current study was to develop a diagnostic set for the detection of respiratory viruses with sensitivity as low as 1–10 copies per reaction. Evaluation of the assay using a training clinical sample set showed that viral nucleic acids were identified in ∼76% of cases. To improve assay performance and facilitate the identification of novel species or emerging strains, cultures of fully differentiated human airway epithelium were used to pre-amplify infectious viruses. This additional step resulted in the detection of pathogens in all samples tested. Based on these results it can be hypothesized that the lack of an etiological agent in some clinical samples, both reported previously and observed in the present study, may result not only from the presence of unknown viral species, but also from imperfections in the detection methods used.",2012 Mar 5,"['Pyrc, Krzysztof', 'Stożek, Karol', 'Wojcik, Krzysztof', 'Gawron, Katarzyna', 'Zeglen, Slawomir', 'Karolak, Wojciech', 'Wojarski, Jacek', 'Ochman, Marek', 'Hubalewska-Mazgaj, Magdalena', 'Bochenek, Grazyna', 'Sanak, Marek', 'Zembala, Marian', 'Szczeklik, Andrzej', 'Potempa, Jan']",PLoS One,,,True
f093aa0cf1ddef303ec4c049ab0be105587dd92c,PMC,Mapping Climate Change Vulnerabilities to Infectious Diseases in Europe,http://dx.doi.org/10.1289/ehp.1103805,PMC3295348,22113877,CC0,"Background: The incidence, outbreak frequency, and distribution of many infectious diseases are generally expected to change as a consequence of climate change, yet there is limited regional information available to guide decision making. Objective: We surveyed government officials designated as Competent Bodies for Scientific Advice concerning infectious diseases to examine the degree to which they are concerned about potential effects of climate change on infectious diseases, as well as their perceptions of institutional capacities in their respective countries. Methods: In 2007 and 2009/2010, national infectious disease experts from 30 European Economic Area countries were surveyed about recent and projected infectious disease patterns in relation to climate change in their countries and the national capacity to cope with them. Results: A large majority of respondents agreed that climate change would affect vector-borne (86% of country representatives), food-borne (70%), water-borne (68%), and rodent-borne (68%) diseases in their countries. In addition, most indicated that institutional improvements are needed for ongoing surveillance programs (83%), collaboration with the veterinary sector (69%), management of animal disease outbreaks (66%), national monitoring and control of climate-sensitive infectious diseases (64%), health services during an infectious disease outbreak (61%), and diagnostic support during an epidemic (54%). Conclusions: Expert responses were generally consistent with the peer-reviewed literature regarding the relationship between climate change and vector- and water-borne diseases, but were less so for food-borne diseases. Shortcomings in institutional capacity to manage climate change vulnerability, identified in this assessment, should be addressed in impact, vulnerability, and adaptation assessments.",2012 Mar 23,"['Semenza, Jan C.', 'Suk, Jonathan E.', 'Estevez, Virginia', 'Ebi, Kristie L.', 'Lindgren, Elisabet']",Environ Health Perspect,,,True
64a0b8711c7e7553c8025dc56a843ce601fc029b,PMC,Early Clinical Features of Dengue Virus Infection in Nicaraguan Children: A Longitudinal Analysis,http://dx.doi.org/10.1371/journal.pntd.0001562,PMC3295819,22413033,CC BY,"BACKGROUND: Tens of millions of dengue cases and approximately 500,000 life-threatening complications occur annually. New tools are needed to distinguish dengue from other febrile illnesses. In addition, the natural history of pediatric dengue early in illness in a community-based setting has not been well-defined. METHODS: Data from the multi-year, ongoing Pediatric Dengue Cohort Study of approximately 3,800 children aged 2–14 years in Managua, Nicaragua, were used to examine the frequency of clinical signs and symptoms by day of illness and to generate models for the association of signs and symptoms during the early phase of illness and over the entire course of illness with testing dengue-positive. Odds ratios (ORs) and 95% confidence intervals were calculated using generalized estimating equations (GEE) for repeated measures, adjusting for age and gender. RESULTS: One-fourth of children who tested dengue-positive did not meet the WHO case definition for suspected dengue. The frequency of signs and symptoms varied by day of illness, dengue status, and disease severity. Multivariable GEE models showed increased odds of testing dengue-positive associated with fever, headache, retro-orbital pain, myalgia, arthralgia, rash, petechiae, positive tourniquet test, vomiting, leukopenia, platelets ≤150,000 cells/mL, poor capillary refill, cold extremities and hypotension. Estimated ORs tended to be higher for signs and symptoms over the course of illness compared to the early phase of illness. CONCLUSIONS: Day-by-day analysis of clinical signs and symptoms together with longitudinal statistical analysis showed significant associations with testing dengue-positive and important differences during the early phase of illness compared to the entire course of illness. These findings stress the importance of considering day of illness when developing prediction algorithms for real-time clinical management.",2012 Mar 6,"['Biswas, Hope H.', 'Ortega, Oscar', 'Gordon, Aubree', 'Standish, Katherine', 'Balmaseda, Angel', 'Kuan, Guillermina', 'Harris, Eva']",PLoS Negl Trop Dis,,,True
b0988e41e28d6f9269e7198ec419142d0a81c7a3,PMC,Enhanced inhibition of Avian leukosis virus subgroup J replication by multi-target miRNAs,http://dx.doi.org/10.1186/1743-422X-8-556,PMC3296551,22188662,CC BY,"BACKGROUND: Avian leukosis virus (ALV) is a major infectious disease that impacts the poultry industry worldwide. Despite intensive efforts, no effective vaccine has been developed against ALV because of mutations that lead to resistant forms. Therefore, there is a dire need to develop antiviral agents for the treatment of ALV infections and RNA interference (RNAi) is considered an effective antiviral strategy. RESULTS: In this study, the avian leukosis virus subgroup J (ALV-J) proviral genome, including the gag genes, were treated as targets for RNAi. Four pairs of miRNA sequences were designed and synthesized that targeted different regions of the gag gene. The screened target (i.e., the gag genes) was shown to effectively suppress the replication of ALV-J by 19.0-77.3%. To avoid the generation of escape variants during virus infection, expression vectors of multi-target miRNAs were constructed using the multi-target serial strategy (against different regions of the gag, pol, and env genes). Multi-target miRNAs were shown to play a synergistic role in the inhibition of ALV-J replication, with an inhibition efficiency of viral replication ranging from 85.0-91.2%. CONCLUSION: The strategy of multi-target miRNAs might be an effective method for inhibiting ALV replication and the acquisition of resistant mutations.",2011 Dec 22,"['Meng, Qing-Wen', 'Zhang, Zai-Ping', 'Wang, Wei', 'Tian, Jin', 'Xiao, Zhi-Guang']",Virol J,,,True
67f2ba141bcc1bffbd19f77b1aedde25a0f0022b,PMC,Hospital incident command system (HICS) performance in Iran; decision making during disasters,http://dx.doi.org/10.1186/1757-7241-20-14,PMC3296571,22309772,CC BY,"BACKGROUND: Hospitals are cornerstones for health care in a community and must continue to function in the face of a disaster. The Hospital Incident Command System (HICS) is a method by which the hospital operates when an emergency is declared. Hospitals are often ill equipped to evaluate the strengths and vulnerabilities of their own management systems before the occurrence of an actual disaster. The main objective of this study was to measure the decision making performance according to HICS job actions sheets using tabletop exercises. METHODS: This observational study was conducted between May 1st 2008 and August 31st 2009. Twenty three Iranian hospitals were included. A tabletop exercise was developed for each hospital which in turn was based on the highest probable risk. The job action sheets of the HICS were used as measurements of performance. Each indicator was considered as 1, 2 or 3 in accordance with the HICS. Fair performance was determined as < 40%; intermediate as 41-70%; high as 71-100% of the maximum score of 192. Descriptive statistics, T-test, and Univariate Analysis of Variance were used. RESULTS: None of the participating hospitals had a hospital disaster management plan. The performance according to HICS was intermediate for 83% (n = 19) of the participating hospitals. No hospital had a high level of performance. The performance level for the individual sections was intermediate or fair, except for the logistic and finance sections which demonstrated a higher level of performance. The public hospitals had overall higher performances than university hospitals (P = 0.04). CONCLUSIONS: The decision making performance in the Iranian hospitals, as measured during table top exercises and using the indicators proposed by HICS was intermediate to poor. In addition, this study demonstrates that the HICS job action sheets can be used as a template for measuring the hospital response. Simulations can be used to assess preparedness, but the correlation with outcome remains to be studied.",2012 Feb 6,"['Djalali, Ahmadreza', 'Castren, Maaret', 'Hosseinijenab, Vahid', 'Khatib, Mahmoud', 'Ohlen, Gunnar', 'Kurland, Lisa']",Scand J Trauma Resusc Emerg Med,,,True
a67a570efab57b9f2492a652c0c17f47546416c4,PMC,Reverse Genetics of SARS-Related Coronavirus Using Vaccinia Virus-Based Recombination,http://dx.doi.org/10.1371/journal.pone.0032857,PMC3296753,22412934,CC BY,"Severe acute respiratory syndrome (SARS) is a zoonotic disease caused by SARS-related coronavirus (SARS-CoV) that emerged in 2002 to become a global health concern. Although the original outbreak was controlled by classical public health measures, there is a real risk that another SARS-CoV could re-emerge from its natural reservoir, either in its original form or as a more virulent or pathogenic strain; in which case, the virus would be difficult to control in the absence of any effective antiviral drugs or vaccines. Using the well-studied SARS-CoV isolate HKU-39849, we developed a vaccinia virus-based SARS-CoV reverse genetic system that is both robust and biosafe. The SARS-CoV genome was cloned in separate vaccinia virus vectors, (vSARS-CoV-5prime and vSARS-CoV-3prime) as two cDNAs that were subsequently ligated to create a genome-length SARS-CoV cDNA template for in vitro transcription of SARS-CoV infectious RNA transcripts. Transfection of the RNA transcripts into permissive cells led to the recovery of infectious virus (recSARS-CoV). Characterization of the plaques produced by recSARS-CoV showed that they were similar in size to the parental SARS-CoV isolate HKU-39849 but smaller than the SARS-CoV isolate Frankfurt-1. Comparative analysis of replication kinetics showed that the kinetics of recSARS-CoV replication are similar to those of SARS-CoV Frankfurt-1, although the titers of virus released into the culture supernatant are approximately 10-fold less. The reverse genetic system was finally used to generate a recSARS-CoV reporter virus expressing Renilla luciferase in order to facilitate the analysis of SARS-CoV gene expression in human dendritic cells (hDCs). In parallel, a Renilla luciferase gene was also inserted into the genome of human coronavirus 229E (HCoV-229E). Using this approach, we demonstrate that, in contrast to HCoV-229E, SARS-CoV is not able to mediate efficient heterologous gene expression in hDCs.",2012 Mar 7,"['van den Worm, Sjoerd H. E.', 'Eriksson, Klara Kristin', 'Zevenhoven, Jessika C.', 'Weber, Friedemann', 'Züst, Roland', 'Kuri, Thomas', 'Dijkman, Ronald', 'Chang, Guohui', 'Siddell, Stuart G.', 'Snijder, Eric J.', 'Thiel, Volker', 'Davidson, Andrew D.']",PLoS One,,,True
5d7698a990270f5ebfa2c879d56187116acc7646,PMC,A placebo-controlled trial of Korean red ginseng extract for preventing Influenza-like illness in healthy adults,http://dx.doi.org/10.1186/1472-6882-12-10,PMC3297520,22314101,CC BY,"ABSTRACTS: BACKGROUND: Standardized Korean red ginseng extract has become the best-selling influenza-like illness (ILI) remedy in Korea, yet much controversy regarding the efficacy of the Korean red ginseng (KRG) in reducing ILI incidence remains. The aim of the study is to assess the efficacy of the KRG extract on the ILI incidence in healthy adults. METHODS/DESIGN: We will conduct a randomized, double-blind, placebo-controlled study at the onset of the influenza seasons. A total of 100 subjects 30-70 years of age will be recruited from the general populations. The subjects will be instructed to take 9 capsules per day of either the KRG extract or a placebo for a period of 3 months. The primary outcome measure is to assess the frequency of ILI onset in participated subjects. Secondary variable measures will be included severity and duration of ILI symptoms. The ILI symptoms will be scored by subjects using a 4-point scale. DISCUSSION: This study is a randomized placebo controlled trial to evaluate the efficacy of the KRG extract compared to placebo and will be provided valuable new information about the clinical and physiological effects of the KRG extract on reduction of ILI incidence including flu and upper respiratory tract infections. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if KRG extract can be shown to be an effective reduction strategy in ILI incidence. TRIAL REGISTRATION: NCT01478009.",2012 Feb 8,"['Ha, Ki-Chan', 'Kim, Min-Gul', 'Oh, Mi-Ra', 'Choi, Eun-Kyung', 'Back, Hyang-Im', 'Kim, Sun-Young', 'Park, Eun-Ok', 'Kwon, Dae-Young', 'Yang, Hye-Jeong', 'Kim, Min-Jeong', 'Kang, Hee-Joo', 'Lee, Ju-Hyung', 'Choi, Kyung-Min', 'Chae, Soo-Wan', 'Lee, Chang-Seop']",BMC Complement Altern Med,,,True
1a12f8004e57cbdc497edada74fdfd8431f4a9eb,PMC,A chemokine gene expression signature derived from meta-analysis predicts the pathogenicity of viral respiratory infections,http://dx.doi.org/10.1186/1752-0509-5-202,PMC3297540,22189154,CC BY,"BACKGROUND: During respiratory viral infections host injury occurs due in part to inappropriate host responses. In this study we sought to uncover the host transcriptional responses underlying differences between high- and low-pathogenic infections. RESULTS: From a compendium of 12 studies that included responses to influenza A subtype H5N1, reconstructed 1918 influenza A virus, and SARS coronavirus, we used meta-analysis to derive multiple gene expression signatures. We compared these signatures by their capacity to segregate biological conditions by pathogenicity and predict pathogenicity in a test data set. The highest-performing signature was expressed as a continuum in low-, medium-, and high-pathogenicity samples, suggesting a direct, analog relationship between expression and pathogenicity. This signature comprised 57 genes including a subnetwork of chemokines, implicating dysregulated cell recruitment in injury. CONCLUSIONS: Highly pathogenic viruses elicit expression of many of the same key genes as lower pathogenic viruses but to a higher degree. This increased degree of expression may result in the uncontrolled co-localization of inflammatory cell types and lead to irreversible host damage.",2011 Dec 22,"['Chang, Stewart T', 'Tchitchek, Nicolas', 'Ghosh, Debashis', 'Benecke, Arndt', 'Katze, Michael G']",BMC Syst Biol,,,True
86fca5af635ee9425e3375140fb48cbe6d429411,PMC,Deep Sequencing for the Detection of Virus-Like Sequences in the Brains of Patients with Multiple Sclerosis: Detection of GBV-C in Human Brain,http://dx.doi.org/10.1371/journal.pone.0031886,PMC3297595,22412845,CC BY,"Multiple sclerosis (MS) is a demyelinating disease of unknown origin that affects the central nervous system of an estimated 400,000 Americans. GBV-C or hepatitis G is a flavivirus that is found in the serum of 1–2% of blood donors. It was originally associated with hepatitis, but is now believed to be a relatively non-pathogenic lymphotropic virus. Fifty frozen specimens from the brains of deceased persons affected by MS were obtained along with 15 normal control brain specimens. RNA was extracted and ribosomal RNAs were depleted before sequencing on the Illumina GAII. These 36 bp reads were compared with a non-redundant database derived from the 600,000+ viral sequences in GenBank organized into 4080 taxa. An individual read successfully aligned to the viral database was considered to be a “hit”. Normalized MS specimen hit rates for each viral taxon were compared to the distribution of hits in the normal controls. Seventeen MS and 11 control brain extracts were sequenced, yielding 4–10 million sequences (“reads”) each. Over-representation of sequence from at least one of 12 viral taxa was observed in 7 of the 17 MS samples. Sequences resembling other viruses previously implicated in the pathogenesis of MS were not significantly enriched in any of the diseased brain specimens. Sequences from GB virus C (GBV-C), a flavivirus not previously isolated from brain, were enriched in one of the MS samples. GBV-C in this brain specimen was confirmed by specific amplification in this single MS brain specimen, but not in the 30 other MS brain samples available. The entire 9.4 kb sequence of this GBV-C isolate is reported here. This study shows the feasibility of deep sequencing for the detection of occult viral infections in the brains of deceased persons with MS. The first isolation of GBV-C from human brain is reported here.",2012 Mar 8,"['Kriesel, John D.', 'Hobbs, Maurine R.', 'Jones, Brandt B.', 'Milash, Brett', 'Nagra, Rashed M.', 'Fischer, Kael F.']",PLoS One,,,True
09ccb3b9fece55e72c3acb85c4259de62a9c9e0c,PMC,Association of herd BRSV and BHV-1 seroprevalence with respiratory disease and reproductive performance in adult dairy cattle,http://dx.doi.org/10.1186/1751-0147-54-4,PMC3298528,22289165,CC BY,"BACKGROUND: The aim of this study was to detect the associations between bovine herpesvirus 1 (BHV-1) status of a herd and respiratory disease (BRD) occurrence and reproductive performance in pregnant heifers and cows. The association between management-related factors and higher BRD occurrence was also estimated. METHODS: Serum samples, collected from cows and youngstock from 103 dairy cattle herds, were analyzed for antibodies against BHV-1, bovine respiratory syncytial virus (BRSV), bovine viral diarrhoea virus (BVDV), and Mycoplasma bovis. A questionnaire was used to collect data concerning herd management factors and reproductive performance, as well as the occurrence of clinical signs of respiratory disease in the last two years, as evaluated by the veterinarian or farm manager. Multiple correspondence analysis (MCA) and logistic regression analysis were performed to identify and quantify the risk factors. RESULTS: A low to moderate prevalence (1-49%) of BRSV antibodies among youngstock was associated with a high occurrence of respiratory disease (OR = 6.2, p = 0.010) in cows and in-calf heifers. Employees of the farm may participate in the spread of such disease. Larger herd size, loose-housing of cows, housing youngstock separately from cows until pregnancy, and purchasing new animals were factors possibly related to a high occurrence of respiratory disease symptoms in pregnant heifers and cows. The highest risk of abortions (> 1.3%) and increased insemination index (number of inseminations per pregnancy) (> 1.9) occurred in herds with a moderate prevalence of BHV-1 antibodies (1-49%) in cows. CONCLUSIONS: BHV-1 was not associated with acute respiratory disease in adult dairy cattle, however was significantly related to reproductive performance. BRSV possesses the main role in respiratory disease complex in adult dairy cattle.",2012 Jan 30,"['Raaperi, Kerli', 'Bougeard, Stephanie', 'Aleksejev, Annely', 'Orro, Toomas', 'Viltrop, Arvo']",Acta Vet Scand,,,True
6b749617eb4a9f2760720a1b2a061cd0d45f9e3f,PMC,Enhancement of anti-murine colon cancer immunity by fusion of a SARS fragment to a low-immunogenic carcinoembryonic antigen,http://dx.doi.org/10.1186/1480-9222-14-2,PMC3298716,22304896,CC BY,"BACKGROUND: It is widely understood that tumor cells express tumor-associated antigens (TAAs), of which many are usually in low immunogenicity; for example, carcinoembryonic antigen (CEA) is specifically expressed on human colon cancer cells and is viewed as a low-immunogenic TAA. How to activate host immunity against specific TAAs and to suppress tumor growth therefore becomes important in cancer therapy development. RESULTS: To enhance the immune efficiency of CEA in mice that received, we fused a partial CEA gene with exogenous SARS-CoV fragments. Oral vaccination of an attenuated Salmonella typhimurium strain transformed with plasmids encoding CEA-SARS-CoV fusion gene into BALB/c mice elicited significant increases in TNF-α and IL-10 in the serum. In addition, a smaller tumor volume was observed in CT26/CEA-bearing mice who received CEA-SARS-CoV gene therapy in comparison with those administered CEA alone. CONCLUSION: The administration of fusing CEA-SARS-CoV fragments may provide a promising strategy for strengthening the anti-tumor efficacy against low-immunogenic endogenous tumor antigens.",2012 Feb 3,"['Lin, Chen-Si', 'Kao, Shih-Han', 'Chen, Yu-Cheng', 'Li, Chi-Han', 'Hsieh, Yuan-Ting', 'Yang, Shang-Chih', 'Wu, Chang-Jer', 'Lee, Ru-Ping', 'Liao, Kuang-Wen']",Biol Proced Online,,,True
9151f784207180e12703758211d31c6d0ee84423,PMC,Evaluation of immune responses to porcine reproductive and respiratory syndrome virus in pigs during early stage of infection under farm conditions,http://dx.doi.org/10.1186/1743-422X-9-45,PMC3298799,22340040,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) causes chronic, economically devastating disease in pigs of all ages. Frequent mutations in the viral genome result in viruses with immune escape mutants. Irrespective of regular vaccination, control of PRRSV remains a challenge to swine farmers. In PRRSV-infected pigs, innate cytokine IFN-α is inhibited and the adaptive arm of the immunity is delayed. To elucidate both cellular and innate cytokine responses at very early stages of PRRSV infection, seven weeks old pigs maintained on a commercial pig farm were infected and analyzed. RESULTS: One pig in a pen containing 25 pigs was PRRSV infected and responses from this pig and one penmate were assessed two days later. All the infected and a few of the contact neighbor pigs were viremic. At day 2 post-infection, approximately 50% of viremic pigs had greater than 50% reduction in NK cell-mediated cytotoxicity, and nearly a 1-fold increase in IFN-α production was detected in blood of a few pigs. Enhanced secretion of IL-4 (in ~90%), IL-12 (in ~40%), and IL-10 (in ~20%) (but not IFN-γ) in PRRSV infected pigs was observed. In addition, reduced frequency of myeloid cells, CD4(-)CD8(+ )T cells, and CD4(+)CD8(+ )T cells and upregulated frequency of lymphocytes bearing natural T regulatory cell phenotype were detected in viremic pigs. Interestingly, all viremic contact pigs also had comparable immune cell modulations. CONCLUSION: Replicating PRRSV in both infected and contact pigs was found to be responsible for rapid modulation in NK cell-meditated cytotoxicity and alteration in the production of important immune cytokines. PRRSV-induced immunological changes observed simultaneously at both cellular and cytokine levels early post-infection appear to be responsible for the delay in generation of adaptive immunity. As the study was performed in pigs maintained under commercial environmental conditions, this study has practical implications in design of protective vaccines.",2012 Feb 16,"['Dwivedi, Varun', 'Manickam, Cordelia', 'Binjawadagi, Basavaraj', 'Linhares, Daniel', 'Murtaugh, Michael P', 'Renukaradhya, Gourapura J']",Virol J,,,True
210ebd55fd095ff2fb393e871fea70815a9ead75,PMC,RNA interference targeting virion core protein ORF095 inhibits Goatpox virus replication in Vero cells,http://dx.doi.org/10.1186/1743-422X-9-48,PMC3298800,22340205,CC BY,"BACKGROUND: Goatpox is an economically important disease in goat and sheep-producing areas of the world. Many vaccine strategies developed to control the disease are not yet completely successful. Hairpin expression vectors have been used to induce gene silencing in a large number of studies on viruses. However, none of these studies has been attempted to study GTPV. In the interest of exploiting improved methods to control goat pox, it is participated that RNAi may provide effective protection against GTPV. In this study we show the suppression of Goatpox virus (GTPV) replication via knockdown of virion core protein using RNA interference. RESULTS: Four short interfering RNA (siRNA) sequences (siRNA-61, siRNA-70, siRNA-165 and siRNA-296) against a region of GTPV ORF095 were selected. Sense and antisense siRNA-encoding sequences separated by a hairpin loop sequence were designed as short hairpin RNA (shRNA) expression cassettes under the control of a human U6 promoter. ORF095 amplicon was generated using PCR, and then cloned into pEGFP-N1 vector, named as p095/EGFP. p095/EGFP and each of the siRNA expression cassettes (p61, p70, p165 and p296) were co-transfected into BHK-21 cells. Fluorescence detection, flow cytometric analysis, retro transcription PCR (RT-PCR) and real time PCR were used to check the efficiency of RNAi. The results showed that the ORF095-specific siRNA-70 effectively down-regulated the expression of ORF095. When Vero cells were transfected with shRNA expression vectors (p61/GFP, p70/GFP, p165/GFP and p296/GFP) and then infected with GTPV, GTPV-ORF095-70 was found to be the most effective inhibition site in decreasing cytopathic effect (CPE) induced by GTPV. The results presented here indicated that DNA-based siRNA could effectively inhibit the replication of GTPV (approximately 463. 5-fold reduction of viral titers) on Vero cells. CONCLUSIONS: This study demonstrates that vector-based shRNA methodology can effectively inhibit GTPV replication on Vero cells. Simultaneously, this work represents a strategy for controlling goatpox, potentially facilitating new experimental approaches in the analysis of both viral and cellular gene functions during of GTPV infection.",2012 Feb 17,"['Zhao, Zhixun', 'Wu, Guohua', 'Zhu, Xueliang', 'Yan, Xinmin', 'Dou, Yongxi', 'Li, Jian', 'Zhu, Haixia', 'Zhang, Qiang', 'Cai, Xuepeng']",Virol J,,,True
6b20f25b48785e488fb280a76ec8f1da3bf8e2a0,PMC,Resveratrol Inhibits KSHV Reactivation by Lowering the Levels of Cellular EGR-1,http://dx.doi.org/10.1371/journal.pone.0033364,PMC3299779,22428032,CC BY,"In the field of herpesvirus research, the exact molecular mechanism by which such viruses reactivate from latency remains elusive. Kaposi's sarcoma-associated herpesvirus (KSHV) primarily exists in a latent state, while only 1–3% of cells support lytic infection at any specific time. KSHV reactivation from latency is an exceedingly intricate process mediated by the integration of viral and cellular factors. Previously, our lab has described early growth response-1 (Egr-1) as an essential component for the KSHV reactivation process via its ability to mediate transcription of KSHV ORF50, the gene encoding for replication and transcription activator (RTA), a viral component known to control the switch from latent to lytic infection. In here, electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) experiments revealed that Egr-1 binds KSHV ORF50 promoter (ORF50P) in at least two different GC-rich binding domains. Expression profiles of cellular egr-1 and KSHV-encoded ORF50 follow a similar pattern during de novo KSHV infection. Over-expressing Egr-1, a signaling component downstream of Raf>MEK>ERK1/2, in KSHV-infected cells activates KSHV lytic replication. Through performing more physiologically relevant experiments, we analyzed the effect of a dietary supplement containing resveratrol on KSHV-infected cells. Our results, for the first time, demonstrate resveratrol to act in lowering ERK1/2 activity and expression of Egr-1 in KSHV-infected cells, resulting in the suppression of virus reactivation from latency. Taken together, these findings will undoubtedly contribute to future studies on not only combating KSHV related disease conditions, but also on other herpesviruses-induced pathogenesis.",2012 Mar 12,"['Dyson, Ossie F.', 'Walker, Lia R.', 'Whitehouse, Adrian', 'Cook, Paul P.', 'Akula, Shaw M.']",PLoS One,,,True
aa89440c172e206c9cdd2f77373ed2b4d1a6b975,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,True
eedef997878564c9d1bd4c183b47daf16d94b52b,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
8051974f7fec24ba5c8dbdf3d5e5b18bfe18c32f,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
f160d134af9e408a52589be1dd6930387d63e288,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
1eefce8aeb42f9e7f7dbe2cc126c89ef74b7c3f5,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
78e91bc7155b4224150017b25ab97804f6c72031,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
44c09bd45e9cee534cfd848c7d182f7dfbbf1e42,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
9fd90139397a0f97a1d5f0caafb98b4f43ced130,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
5679834ba10a936a2f80d6b86bdc9ef3c150a37a,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
71b8d5b1b6326d49737ff53f2e846ed5e1a1bf66,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
7483b73912b2aed3addf19d4f44f45f4b2dcb669,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
f86fb93797c28a8667c57817a5b3cc73454e05f1,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
3f8919e9a281276e8d3acdb9050c88c4000abee7,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
d3ae818d64c0e37d7235d1acbecef4364a460c2b,PMC,Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese,http://dx.doi.org/10.1371/journal.pone.0033389,PMC3299784,22428042,CC BY,"BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8×10(−10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)—POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)—and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.",2012 Mar 12,"['Nakano, Masakazu', 'Ikeda, Yoko', 'Tokuda, Yuichi', 'Fuwa, Masahiro', 'Omi, Natsue', 'Ueno, Morio', 'Imai, Kojiro', 'Adachi, Hiroko', 'Kageyama, Masaaki', 'Mori, Kazuhiko', 'Kinoshita, Shigeru', 'Tashiro, Kei']",PLoS One,,,False
e9d32ac6db6f898b035aab6d4357342c3ae2442b,PMC,A Surveillance System to Reduce Transmission of Pandemic H1N1 (2009) Influenza in a 2600-Bed Medical Center,http://dx.doi.org/10.1371/journal.pone.0032731,PMC3302803,22427871,CC BY,"BACKGROUND: Concerns have been raised about how the transmission of emerging infectious diseases from patients to healthcare workers (HCWs) and vice versa could be recognized and prevented in a timely manner. An effective strategy to block transmission of pandemic H1N1 (2009) influenza in HCWs is important. METHODOLOGY/PRINCIPAL FINDINGS: An infection control program was implemented to survey and prevent nosocomial outbreaks of H1N1 (2009) influenza at a 2,600-bed, tertiary-care academic hospital. In total, 4,963 employees at Kaohsiung Chang Gung Memorial Hospital recorded their temperature and received online education on control practices for influenza infections. Administration records provided vaccination records and occupational characteristics of all HCWs. Early recognition of a pandemic H1N1 (2009) influenza case was followed by a semi-structured questionnaire to analyze possible routes of patient contact, household contact, or unspecified contact. Surveillance spanned August 1, 2009 to January 31, 2010; 51 HCWs were confirmed to have novel H1N1 (2009) influenza by quantitative real-time reverse transcription polymerase chain reaction. Prevalence of patient contact, household contact, or unspecified contact infection was 13.7% (7/51), 13.7% (7/51), and 72.5% (37/51), respectively. The prevalence of the novel H1N1 infection was significantly lower among vaccinated HCWs than among unvaccinated HCWs (p<0.001). Higher viral loads in throat swabs were found in HCWs with patient and household contact infection than in those with unspecified contact infection (4.15 vs. 3.53 copies/mL, log(10), p = 0.035). CONCLUSION: A surveillance system with daily temperature recordings and online education for HCWs is important for a low attack rate of H1N1 (2009) influenza transmission before H1N1 (2009) influenza vaccination is available, and the attack rate is further decreased after mass vaccination. Unspecified contact infection rates were significantly higher than that of patient contact and household contact infection, highlighting the need for public education of influenza transmission in addition to hospital infection control.",2012 Mar 13,"['Chu, Tsui-Ping', 'Li, Chung-Chen', 'Wang, Lin', 'Hsu, Li-Wen', 'Eng, Hock-Liew', 'You, Huey-Ling', 'Liu, Jien-Wei', 'Wei, Chi-Chen', 'Chang, Ling-Sai', 'Lee, Ing-Kit', 'Yang, Kuender D.']",PLoS One,,,True
5ac423d77382c035d9ba1f51ed94d524d1a9ec7f,PMC,Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis,http://dx.doi.org/10.1371/journal.pone.0033174,PMC3303816,22432004,CC BY,"BACKGROUND: Pandemic and seasonal respiratory viruses are a major global health concern. Given the genetic diversity of respiratory viruses and the emergence of drug resistant strains, the targeted disruption of human host-virus interactions is a potential therapeutic strategy for treating multi-viral infections. The availability of large-scale genomic datasets focused on host-pathogen interactions can be used to discover novel drug targets as well as potential opportunities for drug repositioning. METHODS/RESULTS: In this study, we performed a large-scale analysis of microarray datasets involving host response to infections by influenza A virus, respiratory syncytial virus, rhinovirus, SARS-coronavirus, metapneumonia virus, coxsackievirus and cytomegalovirus. Common genes and pathways were found through a rigorous, iterative analysis pipeline where relevant host mRNA expression datasets were identified, analyzed for quality and gene differential expression, then mapped to pathways for enrichment analysis. Possible repurposed drugs targets were found through database and literature searches. A total of 67 common biological pathways were identified among the seven different respiratory viruses analyzed, representing fifteen laboratories, nine different cell types, and seven different array platforms. A large overlap in the general immune response was observed among the top twenty of these 67 pathways, adding validation to our analysis strategy. Of the top five pathways, we found 53 differentially expressed genes affected by at least five of the seven viruses. We suggest five new therapeutic indications for existing small molecules or biological agents targeting proteins encoded by the genes F3, IL1B, TNF, CASP1 and MMP9. Pathway enrichment analysis also identified a potential novel host response, the Parkin-Ubiquitin Proteasomal System (Parkin-UPS) pathway, which is known to be involved in the progression of neurodegenerative Parkinson's disease. CONCLUSIONS: Our study suggests that multiple and diverse respiratory viruses invoke several common host response pathways. Further analysis of these pathways suggests potential opportunities for therapeutic intervention.",2012 Mar 14,"['Smith, Steven B.', 'Dampier, William', 'Tozeren, Aydin', 'Brown, James R.', 'Magid-Slav, Michal']",PLoS One,,,True
2305cbae32a50cf9923356cd30ca3152944d6d38,PMC,Both TLR2 and TRIF Contribute to Interferon-β Production during Listeria Infection,http://dx.doi.org/10.1371/journal.pone.0033299,PMC3303824,22432012,CC BY,"Synthesis of interferon-β (IFN-β) is an innate response to cytoplasmic infection with bacterial pathogens. Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-β synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation. Here, we examined signaling requirements for the massive IFN-β production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, ΔpgdA, which is unable to modify its peptidoglycan. We report the identification of unconventional signaling pathways to the IFN-β gene, requiring TLR2 and bacterial internalization. Induction of IFN-β was independent of the Mal/TIRAP adaptor protein but required TRIF and the transcription factors IRF3 and IRF7. These pathways were stimulated to a lesser degree by wild-type L. monocytogenes. They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages. The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-β gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-β gene expression.",2012 Mar 14,"['Aubry, Camille', 'Corr, Sinéad C.', 'Wienerroither, Sebastian', 'Goulard, Céline', 'Jones, Ruth', 'Jamieson, Amanda M.', 'Decker, Thomas', ""O'Neill, Luke A. J."", 'Dussurget, Olivier', 'Cossart, Pascale']",PLoS One,,,True
59f0dcb0a9c96b60a795162ec2230238896a96e3,PMC,Impact of Preexisting Adenovirus Vector Immunity on Immunogenicity and Protection Conferred with an Adenovirus-Based H5N1 Influenza Vaccine,http://dx.doi.org/10.1371/journal.pone.0033428,PMC3303828,22432020,CC0,"The prevalence of preexisting immunity to adenoviruses in the majority of the human population might adversely impact the development of adaptive immune responses against adenovirus vector-based vaccines. To address this issue, we primed BALB/c mice either intranasally (i.n.) or intramuscularly (i.m.) with varying doses of wild type (WT) human adenovirus subtype 5 (HAd5). Following the development of immunity against HAd5, we immunized animals via the i.n. or i.m. route of inoculation with a HAd vector (HAd-HA-NP) expressing the hemagglutinin (HA) and nucleoprotein (NP) of A/Vietnam/1203/04 (H5N1) influenza virus. The immunogenicity and protection results suggest that low levels of vector immunity (<520 virus-neutralization titer) induced by priming mice with up to 10(7) plaque forming units (p.f.u.) of HAd-WT did not adversely impact the protective efficacy of the vaccine. Furthermore, high levels of vector immunity (approximately 1500 virus-neutralization titer) induced by priming mice with 10(8) p.f.u. of HAd-WT were overcome by either increasing the vaccine dose or using alternate routes of vaccination. A further increase in the priming dose to 10(9) p.f.u. allowed only partial protection. These results suggest possible strategies to overcome the variable levels of human immunity against adenoviruses, leading to better utilization of HAd vector-based vaccines.",2012 Mar 14,"['Pandey, Aseem', 'Singh, Neetu', 'Vemula, Sai V.', 'Couëtil, Laurent', 'Katz, Jacqueline M.', 'Donis, Ruben', 'Sambhara, Suryaprakash', 'Mittal, Suresh K.']",PLoS One,,,True
7b00b9f04112c671d8c31227d31b3fea7ca10c7e,PMC,Protein Reporter Bioassay Systems for the Phenotypic Screening of Candidate Drugs: A Mouse Platform for Anti-Aging Drug Screening,http://dx.doi.org/10.3390/s120201648,PMC3304132,22438730,CC BY,"Recent drug discovery efforts have utilized high throughput screening (HTS) of large chemical libraries to identify compounds that modify the activity of discrete molecular targets. The molecular target approach to drug screening is widely used in the pharmaceutical and biotechnology industries, because of the amount of knowledge now available regarding protein structure that has been obtained by computer simulation. The molecular target approach requires that the structure of target molecules, and an understanding of their physiological functions, is known. This approach to drug discovery may, however, limit the identification of novel drugs. As an alternative, the phenotypic- or pathway-screening approach to drug discovery is gaining popularity, particularly in the academic sector. This approach not only provides the opportunity to identify promising drug candidates, but also enables novel information regarding biological pathways to be unveiled. Reporter assays are a powerful tool for the phenotypic screening of compound libraries. Of the various reporter genes that can be used in such assays, those encoding secreted proteins enable the screening of hit molecules in both living cells and animals. Cell- and animal-based screens enable simultaneous evaluation of drug metabolism or toxicity with biological activity. Therefore, drug candidates identified in these screens may have increased biological efficacy and a lower risk of side effects in humans. In this article, we review the reporter bioassay systems available for phenotypic drug discovery.",2012 Feb 7,"['Chiba, Takuya', 'Tsuchiya, Tomoshi', 'Mori, Ryoichi', 'Shimokawa, Isao']",Sensors (Basel),,,True
ef2b8f83d5a3ab8ae35e4b51fea6d3ed9eb49122,PMC,Development of an ELISA-array for simultaneous detection of five encephalitis viruses,http://dx.doi.org/10.1186/1743-422X-9-56,PMC3305475,22369052,CC BY,"Japanese encephalitis virus(JEV), tick-borne encephalitis virus(TBEV), and eastern equine encephalitis virus (EEEV) can cause symptoms of encephalitis. Establishment of accurate and easy methods by which to detect these viruses is essential for the prevention and treatment of associated infectious diseases. Currently, there are still no multiple antigen detection methods available clinically. An ELISA-array, which detects multiple antigens, is easy to handle, and inexpensive, has enormous potential in pathogen detection. An ELISA-array method for the simultaneous detection of five encephalitis viruses was developed in this study. Seven monoclonal antibodies against five encephalitis-associated viruses were prepared and used for development of the ELISA-array. The ELISA-array assay is based on a ""sandwich"" ELISA format and consists of viral antibodies printed directly on 96-well microtiter plates, allowing for direct detection of 5 viruses. The developed ELISA-array proved to have similar specificity and higher sensitivity compared with the conventional ELISAs. This method was validated by different viral cultures and three chicken eggs inoculated with infected patient serum. The results demonstrated that the developed ELISA-array is sensitive and easy to use, which would have potential for clinical use.",2012 Feb 27,"['Kang, Xiaoping', 'Li, Yuchang', 'Fan, Li', 'Lin, Fang', 'Wei, Jingjing', 'Zhu, Xiaolei', 'Hu, Yi', 'Li, Jing', 'Chang, Guohui', 'Zhu, Qingyu', 'Liu, Hong', 'Yang, Yinhui']",Virol J,,,True
70c53ce121228fdd6ba78b20f143736b56f71984,PMC,CXCR7 antagonism prevents axonal injury during experimental autoimmune encephalomyelitis as revealed by in vivo axial diffusivity,http://dx.doi.org/10.1186/1742-2094-8-170,PMC3305694,22145790,CC BY,"BACKGROUND: Multiple Sclerosis (MS) is characterized by the pathological trafficking of leukocytes into the central nervous system (CNS). Using the murine MS model, experimental autoimmune encephalomyelitis (EAE), we previously demonstrated that antagonism of the chemokine receptor CXCR7 blocks endothelial cell sequestration of CXCL12, thereby enhancing the abluminal localization of CXCR4-expressing leukocytes. CXCR7 antagonism led to decreased parenchymal entry of leukocytes and amelioration of ongoing disease during EAE. Of note, animals that received high doses of CXCR7 antagonist recovered to baseline function, as assessed by standard clinical scoring. Because functional recovery reflects axonal integrity, we utilized diffusion tensor imaging (DTI) to evaluate axonal injury in CXCR7 antagonist- versus vehicle-treated mice after recovery from EAE. METHODS: C57BL6/J mice underwent adoptive transfer of MOG-reactive Th1 cells and were treated daily with either CXCR7 antagonist or vehicle for 28 days; and then evaluated by DTI to assess for axonal injury. After imaging, spinal cords underwent histological analysis of myelin and oligodendrocytes via staining with luxol fast blue (LFB), and immunofluorescence for myelin basic protein (MBP) and glutathione S-transferase-π (GST-π). Detection of non-phosphorylated neurofilament H (NH-F) was also performed to detect injured axons. Statistical analysis for EAE scores, DTI parameters and non-phosphorylated NH-F immunofluorescence were done by ANOVA followed by Bonferroni post-hoc test. For all statistical analysis a p < 0.05 was considered significant. RESULTS: In vivo DTI maps of spinal cord ventrolateral white matter (VLWM) axial diffusivities of naïve and CXCR7 antagonist-treated mice were indistinguishable, while vehicle-treated animals exhibited decreased axial diffusivities. Quantitative differences in injured axons, as assessed via detection of non-phosphorylated NH-F, were consistent with axial diffusivity measurements. Overall, qualitative myelin content and presence of oligodendrocytes were similar in all treatment groups, as expected by their radial diffusivity values. Quantitative assessment of persistent inflammatory infiltrates revealed significant decreases within the parenchyma of CXCR7 antagonist-treated mice versus controls. CONCLUSIONS: These data suggest that CXCR7 antagonism not only prevents persistent inflammation but also preserves axonal integrity. Thus, targeting CXCR7 modifies both disease severity and recovery during EAE, suggesting a role for this molecule in both phases of disease.",2011 Dec 6,"['Cruz-Orengo, Lillian', 'Chen, Ying-Jr', 'Kim, Joong Hee', 'Dorsey, Denise', 'Song, Sheng-Kwei', 'Klein, Robyn S']",J Neuroinflammation,,,True
ba3f5979fe991711ff096116b05cdb182ef3aeab,PMC,A Novel High-Throughput Vaccinia Virus Neutralization Assay and Preexisting Immunity in Populations from Different Geographic Regions in China,http://dx.doi.org/10.1371/journal.pone.0033392,PMC3306400,22438922,CC BY,"BACKGROUND: Pre-existing immunity to Vaccinia Tian Tan virus (VTT) resulting from a large vaccination campaign against smallpox prior to the early 1980s in China, has been a major issue for application of VTT-vector based vaccines. It is essential to establish a sensitive and high-throughput neutralization assay to understand the epidemiology of Vaccinia-specific immunity in current populations in China. METHODOLOGY/PRINCIPAL FINDINGS: A new anti-Vaccinia virus (VACV) neutralization assay that used the attenuated replication-competent VTT carrying the firefly luciferase gene of Photinus pyralis (rTV-Fluc) was established and standardized for critical parameters that included the choice of cell line, viral infection dose, and the infection time. The current study evaluated the maintenance of virus-specific immunity after smallpox vaccination by conducting a non-randomized, cross-sectional analysis of antiviral antibody-mediated immune responses in volunteers examined 30–55 years after vaccination. The rTV-Fluc neutralization assay was able to detect neutralizing antibodies (NAbs) against Vaccinia virus without the ability to differentiate strains of Vaccinia virus. We showed that the neutralizing titers measured by our assay were similar to those obtained by the traditional plaque reduction neutralization test (PRNT). Using this assay, we found a low prevalence of NAb to VTT (7.6%) in individuals born before 1980 from Beijing and Anhui provinces in China, and when present, anti-VTT NAb titers were low. No NAbs were detected in all 222 samples from individuals born after 1980. There was no significant difference observed for titer or prevalence by gender, age range and geographic origin. CONCLUSION: A simplified, sensitive, standardized, reproducible, and high-throughput assay was developed for the quantitation of NAbs against different Vaccinia strains. The current study provides useful insights for the future development of VTT-based vaccination in Beijing and Anhui provinces of China.",2012 Mar 16,"['Liu, Qiang', 'Huang, Weijin', 'Nie, Jianhui', 'Zhu, Rong', 'Gao, Dongying', 'Song, Aijing', 'Meng, Shufang', 'Xu, Xuemei', 'Wang, Youchun']",PLoS One,,,True
88a0b7d6447839c09069588d1761364ce9045d61,PMC,The occurrence of Chlamydia spp. in pigs with and without clinical disease,http://dx.doi.org/10.1186/1746-6148-8-9,PMC3307427,22280482,CC BY,"BACKGROUND: Within the genera Chlamydia, the development of refined diagnostic techniques has allowed the identification of four species that are capable of infecting pigs. The epidemiology, clinical, and zoonotic impacts of these species are however largely unknown. The study aimed to investigate the presence of Chlamydia spp. in the intestines of growing pigs and in conjunctival swabs from finisher pigs, and relate the findings to clinical signs. RESULTS: By histology, 20 of 48 pigs had intestinal lesions that may be consistent with chlamydial infection. By PCR, forty-six of the pigs were positive whereas two samples were inhibited. Sequencing of 19 DNA extracts identified these as Chlamydia suis. By immunohistochemistry, 32 of 44 samples were positive and a significant relationship was detected between macroscopically visible intestinal lesions and a high degree of infection. By real-time PCR, a significant difference was detected between pigs with and without conjunctivitis when a Ct value of 36 was employed but not when a Ct value of 38 was employed. CONCLUSIONS: Chlamydia suis was demonstrated in most samples and overall, no correlation to clinical signs was detected. However, a correlation was noted between samples with a high degree of infection and the presence of clinical signs. It is possible, that the intensive pig production systems studied might predispose for the transmission and maintenance of the infection thus increasing the infectious load and the risk for disease in the pig.",2012 Jan 26,"['Englund, Stina', 'Hård af Segerstad, Carl', 'Arnlund, Frida', 'Westergren, Eva', 'Jacobson, Magdalena']",BMC Vet Res,,,True
b85671451a6132068f92e5da9590cbc9ee5867d5,PMC,Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia,http://dx.doi.org/10.1371/journal.pone.0032112,PMC3307712,22442662,CC BY,"Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (I(SC)) in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A(2B) adenosine receptor (A(2B)AR), largely abolished the adenosine-stimulated chloride transport, suggesting that A(2B)AR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2B)AR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections.",2012 Mar 19,"['Raju, Sammeta V.', 'Wang, Guoshun']",PLoS One,,,True
50fa3228f8067d61d3debffbe06c53deaf9dc863,PMC,Recombinant Vesicular Stomatitis Virus Vaccine Vectors Expressing Filovirus Glycoproteins Lack Neurovirulence in Nonhuman Primates,http://dx.doi.org/10.1371/journal.pntd.0001567,PMC3308941,22448291,CC0,"The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses an individual filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV) GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV) GP; three animals received rVSV-wild type (wt) vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use.",2012 Mar 20,"['Mire, Chad E.', 'Miller, Andrew D.', 'Carville, Angela', 'Westmoreland, Susan V.', 'Geisbert, Joan B.', 'Mansfield, Keith G.', 'Feldmann, Heinz', 'Hensley, Lisa E.', 'Geisbert, Thomas W.']",PLoS Negl Trop Dis,,,True
af2a0da4beb166ca0b189ee6282120c9b664ea79,PMC,High Fidelity Processing and Activation of the Human α-Defensin HNP1 Precursor by Neutrophil Elastase and Proteinase 3,http://dx.doi.org/10.1371/journal.pone.0032469,PMC3308943,22448222,CC BY,"The azurophilic granules of human neutrophils contain four α-defensins called human neutrophil peptides (HNPs 1–4). HNPs are tridisulfide-linked antimicrobial peptides involved in the intracellular killing of organisms phagocytosed by neutrophils. The peptides are produced as inactive precursors (proHNPs) which are processed to active microbicides by as yet unidentified convertases. ProHNP1 was expressed in E. coli and the affinity-purified propeptide isolated as two species, one containing mature HNP1 sequence with native disulfide linkages (“folded proHNP1”) and the other containing non-native disulfide linked proHNP1 conformers (misfolded proHNP1). Native HNP1, liberated by CNBr treatment of folded proHNP1, was microbicidal against Staphylococcus aureus, but the peptide derived from misfolded proHNP1 was inactive. We hypothesized that neutrophil elastase (NE), proteinase 3 (PR3) or cathepsin G (CG), serine proteases that co-localize with HNPs in azurophil granules, are proHNP1 activating convertases. Folded proHNP1 was converted to mature HNP1 by both NE and PR3, but CG generated an HNP1 variant with an N-terminal dipeptide extension. NE and PR3 cleaved folded proHNP1 to produce a peptide indistinguishable from native HNP1 purified from neutrophils, and the microbicidal activities of in vitro derived and natural HNP1 peptides were equivalent. In contrast, misfolded proHNP1 conformers were degraded extensively under the same conditions. Thus, NE and PR3 possess proHNP1 convertase activity that requires the presence of the native HNP1 disulfide motif for high fidelity activation of the precursor in vitro.",2012 Mar 20,"['Tongaonkar, Prasad', 'Golji, Amir E.', 'Tran, Patti', 'Ouellette, André J.', 'Selsted, Michael E.']",PLoS One,,,True
9903fc2ee43aca54acf2469fdc2ae8de2e62a09c,PMC,Foxp3(+) Regulatory T Cells Control Persistence of Viral CNS Infection,http://dx.doi.org/10.1371/journal.pone.0033989,PMC3309005,22448284,CC BY,"We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified) mice and recombinant measles virus (MV). Using this model infection we investigated the role of regulatory T cells (Tregs) as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4(+) CD25(+) Foxp3(+) Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8(+) T cells predominantly recognising the H-2D(b)-presented viral hemagglutinin epitope MV-H(22–30) (RIVINREHL) were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p.) application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT) in DEREG (depletion of regulatory T cells)-mice induced an increase of virus-specific CD8(+) effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.",2012 Mar 20,"['Reuter, Dajana', 'Sparwasser, Tim', 'Hünig, Thomas', 'Schneider-Schaulies, Jürgen']",PLoS One,,,True
888a2dcee2c34b07d19a0528febb54aad70bdf00,PMC,Surveillance of Airborne Adenovirus and Mycoplasma pneumoniae in a Hospital Pediatric Department,http://dx.doi.org/10.1371/journal.pone.0033974,PMC3309934,22470502,CC BY,This investigation evaluated the distributions of airborne adenovirus and Mycoplasma pneumoniae in public areas in the pediatric department of Children's Hospital in northern Taiwan. The airborne viral and bacterial concentrations were evaluated twice a week for a year using filter sampling with an airflow rate of 12 liters per minute for eight hours in the pediatric outpatient department and 24 hours in the pediatric emergency room. Real-time polymerase chain reaction assays were conducted for analysis. Approximately 18% of the air samples from the pediatric emergency room were found to contain adenovirus. Approximately forty-six percent of the air samples from the pediatric outpatient department contained Mycoplasma pneumoniae DNA products. High detection rates of airborne adenovirus DNA were obtained in July and August in the pediatric public areas. Airborne Mycoplasma pneumoniae was detected only in July in the pediatric emergency room and the peak levels were found from August to January in the pediatric outpatient department. Airborne particles that contained adenovirus and Mycoplasma pneumoniae were the most prevalent in the pediatric public areas. The potential relationship between these airborne viral/bacterial particles and human infection should be examined further. Keywords: adenovirus; Mycoplasma pneumoniae; filter sampling; real-time polymerase chain reaction; hospital; pediatric public areas.,2012 Mar 21,"['Wan, Gwo-Hwa', 'Huang, Chung-Guei', 'Huang, Yhu-Chering', 'Huang, Ju-Ping', 'Yang, Su-Li', 'Lin, Tzou-Yien', 'Tsao, Kuo-Chien']",PLoS One,,,True
5fa62370245d4ad73220d6f42f8cb66064627aaa,PMC,Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells,http://dx.doi.org/10.1371/journal.ppat.1002584,PMC3310792,22457619,CC BY,"Dengue virus causes ∼50–100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.",2012 Mar 22,"['Perera, Rushika', 'Riley, Catherine', 'Isaac, Giorgis', 'Hopf-Jannasch, Amber S.', 'Moore, Ronald J.', 'Weitz, Karl W.', 'Pasa-Tolic, Ljiljana', 'Metz, Thomas O.', 'Adamec, Jiri', 'Kuhn, Richard J.']",PLoS Pathog,,,True
006bfa7dbe2caea917efd90843b0882c402abfce,PMC,Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells,http://dx.doi.org/10.1371/journal.ppat.1002584,PMC3310792,22457619,CC BY,"Dengue virus causes ∼50–100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.",2012 Mar 22,"['Perera, Rushika', 'Riley, Catherine', 'Isaac, Giorgis', 'Hopf-Jannasch, Amber S.', 'Moore, Ronald J.', 'Weitz, Karl W.', 'Pasa-Tolic, Ljiljana', 'Metz, Thomas O.', 'Adamec, Jiri', 'Kuhn, Richard J.']",PLoS Pathog,,,False
d2a7fc6bc3da9aee40450daa3b374b187dbd1948,PMC,Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells,http://dx.doi.org/10.1371/journal.ppat.1002584,PMC3310792,22457619,CC BY,"Dengue virus causes ∼50–100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.",2012 Mar 22,"['Perera, Rushika', 'Riley, Catherine', 'Isaac, Giorgis', 'Hopf-Jannasch, Amber S.', 'Moore, Ronald J.', 'Weitz, Karl W.', 'Pasa-Tolic, Ljiljana', 'Metz, Thomas O.', 'Adamec, Jiri', 'Kuhn, Richard J.']",PLoS Pathog,,,False
c334662c42a52cfaf8f1b3a8af1821230df9b798,PMC,Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells,http://dx.doi.org/10.1371/journal.ppat.1002584,PMC3310792,22457619,CC BY,"Dengue virus causes ∼50–100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.",2012 Mar 22,"['Perera, Rushika', 'Riley, Catherine', 'Isaac, Giorgis', 'Hopf-Jannasch, Amber S.', 'Moore, Ronald J.', 'Weitz, Karl W.', 'Pasa-Tolic, Ljiljana', 'Metz, Thomas O.', 'Adamec, Jiri', 'Kuhn, Richard J.']",PLoS Pathog,,,False
8dedaee19e09c9fd5a849dda12a4521ea675b1a4,PMC,Accidental Chlorine Gas Intoxication: Evaluation of 39 Patients,http://dx.doi.org/10.4021/jocmr2009.12.1283,PMC3311442,22481989,CC BY,"BACKGROUND: Chlorine is a known pulmonary irritant gas that may cause acute damage in the respiratory system. In this paper, the socio-demographic and clinical characteristics of 39 accidentally exposed patients to chlorine gas are reported and different emergency treatment modalities are also discussed. METHODS: Two emergency departments applications were retrospectively analyzed for evaluation of accidental chlorine gas exposure for year 2007. Patients were classified into 3 groups according to severity of clinical and laboratory findings based on the literature and duration of land of stay in the emergency department. The first group was slightly exposed (discharged within 6 hours), second group moderately exposed (treated and observed for 24 hours), and third group was severely exposed (hospitalized). Most of the patients were initially treated with a combination of humidified oxygen, corticosteroids, and bronchodilators. RESULTS: The average age was 17.03 ± 16.01 years (95% CI). Seven (17.9%) of them were female and 29 (74.4%) were children. Twenty-four patients (61.5%) were included in the first, nine (23.1%) were in second and six (15.4%) were in the third group. The presenting symptoms were cough, nausea, and vomiting and conjunctiva hyperemia for the first group, first groups symptoms plus dyspnea for the second group. Second groups symptoms plus palpitation, weakness and chest tightness were for the third group. Cough and dyspnea were seen in 64.1% and 30.8% of the patients respectively. No patients died. CONCLUSIONS: The authors recommend that non symptomatic or slightly exposed patients do not need any specific treatment or symptomatic treatment is sufficient. KEYWORDS: Accidental; Chlorine exposure; Chlorine gas; Chlorine intoxication; Emergency department",2009 Dec 28,"['Sever, Mustafa', 'Mordeniz, Cengiz', 'Sever, Fidan', 'Dokur, Mehmet']",J Clin Med Res,,,True
16ab54289da4d53548b4cf171a642e19fd81e660,PMC,Descriptive review and evaluation of the functioning of the International Health Regulations (IHR) Annex 2,http://dx.doi.org/10.1186/1744-8603-8-1,PMC3313850,22233652,CC BY,"BACKGROUND: The International Health Regulations (IHRs) (2005) was developed with the aim of governing international responses to public health risks and emergencies. The document requires all 194 World Health Organization (WHO) Member States to detect, assess, notify and report any potential public health emergency of international concern (PHEIC) under specific timelines. Annex 2 of the IHR outlines decision-making criteria for State-appointed National Focal Points (NFP) to report potential PHEICs to the WHO, and is a critical component to the effective functioning of the IHRs. METHODS: The aim of the study was to review and evaluate the functioning of Annex 2 across WHO-reporting States Parties. Specific objectives were to ascertain NFP awareness and knowledge of Annex 2, practical use of the tool, activities taken to implement it, its perceived usefulness and user-friendliness. Qualitative telephone interviews, followed by a quantitative online survey, were administered to NFPs between October, 2009 and February, 2010. RESULTS: A total of 29 and 133 NFPs participated in the qualitative and quantitative studies, respectively. Qualitative interviews found most NFPs had a strong working knowledge of Annex 2; perceived the tool to be relevant and useful for guiding decisions; and had institutionalized management, legislation and communication systems to support it. NFPs also perceived Annex 2 as human and disease-centric, and emphasized its reduced applicability to potential PHEICs involving bioterrorist attacks, infectious diseases among animals, radio-nuclear and chemical spills, and water- or food-borne contamination. Among quantitative survey respondents, 88% reported having excellent/good knowledge of Annex 2; 77% reported always/usually using Annex 2 for assessing potential PHEICs; 76% indicated their country had some legal, regulatory or administrative provisions for using Annex 2; 95% indicated Annex 2 was always/usually useful for facilitating decisions regarding notifiability of potential PHEICs. CONCLUSION: This evaluation, including a large sample of WHO-reporting States Parties, found that the IHR's Annex 2 is perceived as useful for guiding decisions about notifiability of potential PHEICs. There is scope for the WHO to expand training and guidance on application of the IHR's Annex 2 to specific contexts. Continued monitoring and evaluation of the functioning of the IHR is imperative to promoting global health security.",2012 Jan 10,"['Anema, Aranka', 'Druyts, Eric', 'Hollmeyer, Helge G', 'Hardiman, Maxwell C', 'Wilson, Kumanan']",Global Health,,,True
6a776cdff97d90eae72e7f8be666aef3a14224e2,PMC,Membrane Fusion and Cell Entry of XMRV Are pH-Independent and Modulated by the Envelope Glycoprotein's Cytoplasmic Tail,http://dx.doi.org/10.1371/journal.pone.0033734,PMC3313918,22479434,CC BY,"Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus that was originally identified from human prostate cancer patients and subsequently linked to chronic fatigue syndrome. Recent studies showed that XMRV is a recombinant mouse retrovirus; hence, its association with human diseases has become questionable. Here, we demonstrated that XMRV envelope (Env)-mediated pseudoviral infection is not blocked by lysosomotropic agents and cellular protease inhibitors, suggesting that XMRV entry is not pH-dependent. The full length XMRV Env was unable to induce syncytia formation and cell-cell fusion, even in cells overexpressing the viral receptor, XPR1. However, truncation of the C-terminal 21 or 33 amino acid residues in the cytoplasmic tail (CT) of XMRV Env induced substantial membrane fusion, not only in the permissive 293 cells but also in the nonpermissive CHO cells that lack a functional XPR1 receptor. The increased fusion activities of these truncations correlated with their enhanced SU shedding into culture media, suggesting conformational changes in the ectodomain of XMRV Env. Noticeably, further truncation of the CT of XMRV Env proximal to the membrane-spanning domain severely impaired the Env fusogenicity, as well as dramatically decreased the Env incorporations into MoMLV oncoretroviral and HIV-1 lentiviral vectors resulting in greatly reduced viral transductions. Collectively, our studies reveal that XMRV entry does not require a low pH or low pH-dependent host proteases, and that the cytoplasmic tail of XMRV Env critically modulates membrane fusion and cell entry. Our data also imply that additional cellular factors besides XPR1 are likely to be involved in XMRV entry.",2012 Mar 27,"['Côté, Marceline', 'Zheng, Yi-Min', 'Liu, Shan-Lu']",PLoS One,,,True
87795a5783981250b35b32635c37fd2a098c4ed6,PMC,"The Impact of Weather on Influenza and Pneumonia Mortality in New York City, 1975–2002: A Retrospective Study",http://dx.doi.org/10.1371/journal.pone.0034091,PMC3314701,22470518,CC BY,"The substantial winter influenza peak in temperate climates has lead to the hypothesis that cold and/or dry air is a causal factor in influenza variability. We examined the relationship between cold and/or dry air and daily influenza and pneumonia mortality in the cold season in the New York metropolitan area from 1975–2002. We conducted a retrospective study relating daily pneumonia and influenza mortality for New York City and surroundings from 1975–2002 to daily air temperature, dew point temperature (a measure of atmospheric humidity), and daily air mass type. We identified high mortality days and periods and employed temporal smoothers and lags to account for the latency period and the time between infection and death. Unpaired t-tests were used to compare high mortality events to non-events and nonparametric bootstrapped regression analysis was used to examine the characteristics of longer mortality episodes. We found a statistically significant (p = 0.003) association between periods of low dew point temperature and above normal pneumonia and influenza mortality 17 days later. The duration (r = −0.61) and severity (r = −0.56) of high mortality episodes was inversely correlated with morning dew point temperature prior to and during the episodes. Weeks in which moist polar air masses were common (air masses characterized by low dew point temperatures) were likewise followed by above normal mortality 17 days later (p = 0.019). This research supports the contention that cold, dry air may be related to influenza mortality and suggests that warning systems could provide enough lead time to be effective in mitigating the effects.",2012 Mar 28,"['Davis, Robert E.', 'Rossier, Colleen E.', 'Enfield, Kyle B.']",PLoS One,,,True
cf92667ce9f346dd79bc980fdb5d21a5cf6b334a,PMC,Emerging Viruses in the Felidae: Shifting Paradigms,http://dx.doi.org/10.3390/v4020236,PMC3315214,22470834,CC BY,"The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important new evolutionary conclusions implicating these deadly infectious agents in domestic and non-domestic felids.",2012 Feb 7,"['O’Brien, Stephen J.', 'Troyer, Jennifer L.', 'Brown, Meredith A.', 'Johnson, Warren E.', 'Antunes, Agostinho', 'Roelke, Melody E.', 'Pecon-Slattery, Jill']",Viruses,,,True
793ff384663ce5425d0b61619d47fb0b306d7ec1,PMC,Filovirus Entry: A Novelty in the Viral Fusion World,http://dx.doi.org/10.3390/v4020258,PMC3315215,22470835,CC BY,"Ebolavirus (EBOV) and Marburgvirus (MARV) that compose the filovirus family of negative strand RNA viruses infect a broad range of mammalian cells. Recent studies indicate that cellular entry of this family of viruses requires a series of cellular protein interactions and molecular mechanisms, some of which are unique to filoviruses and others are commonly used by all viral glycoproteins. Details of this entry pathway are highlighted here. Virus entry into cells is initiated by the interaction of the viral glycoprotein(1) subunit (GP(1)) with both adherence factors and one or more receptors on the surface of host cells. On epithelial cells, we recently demonstrated that TIM-1 serves as a receptor for this family of viruses, but the cell surface receptors in other cell types remain unidentified. Upon receptor binding, the virus is internalized into endosomes primarily via macropinocytosis, but perhaps by other mechanisms as well. Within the acidified endosome, the heavily glycosylated GP(1) is cleaved to a smaller form by the low pH-dependent cellular proteases Cathepsin L and B, exposing residues in the receptor binding site (RBS). Details of the molecular events following cathepsin-dependent trimming of GP(1) are currently incomplete; however, the processed GP(1) specifically interacts with endosomal/lysosomal membranes that contain the Niemann Pick C1 (NPC1) protein and expression of NPC1 is required for productive infection, suggesting that GP/NPC1 interactions may be an important late step in the entry process. Additional events such as further GP(1) processing and/or reducing events may also be required to generate a fusion-ready form of the glycoprotein. Once this has been achieved, sequences in the filovirus GP(2) subunit mediate viral/cellular membrane fusion via mechanisms similar to those previously described for other enveloped viruses. This multi-step entry pathway highlights the complex and highly orchestrated path of internalization and fusion that appears unique for filoviruses.",2012 Feb 7,"['Hunt, Catherine L.', 'Lennemann, Nicholas J.', 'Maury, Wendy']",Viruses,,,True
bcdceb50d70afda0d8615859b356484af61aab04,PMC,"Specific, simple and rapid detection of porcine circovirus type 2 using the loop-mediated isothermal amplification method",http://dx.doi.org/10.1186/1743-422X-8-126,PMC3315793,21414233,CC BY,"BACKGROUND: Porcine circovirus type 2 (PCV2) is the causative agent of postweaning multisystemic wasting syndrome (PMWS), and porcine dermatitis and nephropathy syndrome (PDNS). It has caused heavy losses in global agriculture in recent decades. Rapid detection of PCV2 is very important for the effective prophylaxis and treatment of PMWS. RESULTS: A loop-mediated isothermal amplification (LAMP) assay was used to detect PCV2 in this study. Three pairs of primers were specially designed for recognizing eight distinct sequences of the ORF2 gene. This gene lies in the PCV2 virus genome sequence, and encodes the Rep protein that is involved in virus replication. Time and temperature conditions for amplification of PCV2 genes were optimized to be 55 min at 59°C. The analysis of clinical samples indicated that the LAMP method was highly sensitive. The detection limit for PCV2 by the LAMP assay was 10 copies, whereas the limit by conventional PCR was 1000 copies. The assay did not cross-react with PCV1, porcine reproductive and respiratory syndrome virus, porcine epidemic diarrhea virus, transmissible gastroenteritis of pigs virus or rotavirus. When 110 samples were tested using the established LAMP system, 95 were detected as positive. CONCLUSION: The newly developed LAMP detection method for PCV2 was more specific, sensitive, rapid and simple than before. It complements and extends previous methods for PCV2 detection and provides an alternative approach for detection of PCV2.",2011 Mar 18,"['Zhao, Kai', 'Shi, Wei', 'Han, Fangting', 'Xu, Yan', 'Zhu, Lianlong', 'Zou, Yong', 'Wu, Xiao', 'Zhu, Hong', 'Tan, Furong', 'Tao, Shiru', 'Tang, Xueming']",Virol J,,,True
3ed400293b6f0963dcffb081e94de5229fb42cc7,PMC,IFITM Proteins Restrict Antibody-Dependent Enhancement of Dengue Virus Infection,http://dx.doi.org/10.1371/journal.pone.0034508,PMC3316688,22479637,CC BY,"Interferon-inducible transmembrane (IFITM) proteins restrict the entry processes of several pathogenic viruses, including the flaviviruses West Nile virus and dengue virus (DENV). DENV infects cells directly or via antibody-dependent enhancement (ADE) in Fc-receptor-bearing cells, a process thought to contribute to severe disease in a secondary infection. Here we investigated whether ADE-mediated DENV infection bypasses IFITM-mediated restriction or whether IFITM proteins can be protective in a secondary infection. We observed that IFITM proteins restricted ADE-mediated and direct infection with comparable efficiencies in a myelogenous leukemia cell line. Our data suggest that IFITM proteins can contribute to control of secondary DENV infections.",2012 Mar 30,"['Chan, Ying Kai', 'Huang, I-Chueh', 'Farzan, Michael']",PLoS One,,,True
ae072e0f04db143d038aa090e714f31e0c8c34bc,PMC,High Viral Load of Human Bocavirus Correlates with Duration of Wheezing in Children with Severe Lower Respiratory Tract Infection,http://dx.doi.org/10.1371/journal.pone.0034353,PMC3316689,22479609,CC BY,"BACKGROUND: Human bocavirus (HBoV) is a newly discovered parvovirus and increasing evidences are available to support its role as an etiologic agent in lower respiratory tract infection (LRTI). The objective of this study is to assess the impact of HBoV viral load on clinical characteristics in children who were HBoV positive and suffered severe LRTI. METHODS: Lower respiratory tract aspirates from 186 hospitalized children with severe LRTI were obtained by bronchoscopy. HBoVs were detected by real-time PCR and other 10 infectious agents were examined using PCR and/or direct fluorescent assay. RESULTS: Thirty-one patients (24.6%) were tested positive for HBoV in the respiratory tract aspirates. Fifteen samples had a high viral load (>10(4) copies/mL) and the other sixteen samples had a low viral load (<10(4) copies/mL). The duration of presented wheezing and hospitalization was longer in children with high viral load of HBoV than that in children with low viral load. The days of wheezing showed a correlation with viral load of HBoV. CONCLUSION: We confirmed that HBoV was frequently detected in patients with severe LRTI. Wheezing was one of the most common symptoms presented by patients with positive HBoV. A high HBoV viral load could be an etiologic agent for LRTI, which led to more severe lower respiratory tract symptom, longer duration of wheezing and hospitalization.",2012 Mar 30,"['Deng, Yu', 'Gu, Xiaoyang', 'Zhao, Xiaodong', 'Luo, Jian', 'Luo, Zhengxiu', 'Wang, Lijia', 'Fu, Zhou', 'Yang, Xiqiang', 'Liu, Enmei']",PLoS One,,,True
8ed0914312a47f0d8c127bc1db47446c1792e1de,PMC,Public health interventions for epidemics: implications for multiple infection waves,http://dx.doi.org/10.1186/1471-2458-11-S1-S2,PMC3317576,21356131,CC BY,"BACKGROUND: Epidemics with multiple infection waves have been documented for some human diseases, most notably during past influenza pandemics. While pathogen evolution, co-infection, and behavioural changes have been proposed as possible mechanisms for the occurrence of subsequent outbreaks, the effect of public health interventions remains undetermined. METHODS: We develop mean-field and stochastic epidemiological models for disease transmission, and perform simulations to show how control measures, such as drug treatment and isolation of ill individuals, can influence the epidemic profile and generate sequences of infection waves with different characteristics. RESULTS: We demonstrate the impact of parameters representing the effectiveness and adverse consequences of intervention measures, such as treatment and emergence of drug resistance, on the spread of a pathogen in the population. If pathogen resistant strains evolve under drug pressure, multiple outbreaks are possible with variability in their characteristics, magnitude, and timing. In this context, the level of drug use and isolation capacity play an important role in the occurrence of subsequent outbreaks. Our simulations for influenza infection as a case study indicate that the intensive use of these interventions during the early stages of the epidemic could delay the spread of disease, but it may also result in later infection waves with possibly larger magnitudes. CONCLUSIONS: The findings highlight the importance of intervention parameters in the process of public health decision-making, and in evaluating control measures when facing substantial uncertainty regarding the epidemiological characteristics of an emerging infectious pathogen. Critical factors that influence population health including evolutionary responses of the pathogen under the pressure of different intervention measures during an epidemic should be considered for the design of effective strategies that address short-term targets compatible with long-term disease outcomes.",2011 Feb 25,"['Wessel, Lindsay', 'Hua, Yi', 'Wu, Jianhong', 'Moghadas, Seyed M']",BMC Public Health,,,True
aae9028bc39c23fd877b0059777933774b7bf2e0,PMC,Increasing the X-ray Diffraction Power of Protein Crystals by Dehydration: The Case of Bovine Serum Albumin and a Survey of Literature Data,http://dx.doi.org/10.3390/ijms13033782,PMC3317743,22489183,CC BY,"Serum albumin is one of the most widely studied proteins. It is the most abundant protein in plasma with a typical concentration of 5 g/100 mL and the principal transporter of fatty acids in plasma. While the crystal structures of human serum albumin (HSA) free and in complex with fatty acids, hemin, and local anesthetics have been characterized, no crystallographic models are available on bovine serum albumin (BSA), presumably because of the poor diffraction power of existing hexagonal BSA crystals. Here, the crystallization and diffraction data of a new BSA crystal form, obtained by the hanging drop method using MPEG 5K as precipitating agent, are presented. The crystals belong to space group C2, with unit-cell parameters a = 216.45 Å, b = 44.72 Å, c = 140.18 Å, β = 114.5°. Dehydration was found to increase the diffraction limit of BSA crystals from ~8 Å to 3.2 Å, probably by improving the packing of protein molecules in the crystal lattice. These results, together with a survey of more than 60 successful cases of protein crystal dehydration, confirm that it can be a useful procedure to be used in initial screening as a method of improving the diffraction limits of existing crystals.",2012 Mar 21,"['Krauss, Irene Russo', 'Sica, Filomena', 'Mattia, Carlo Andrea', 'Merlino, Antonello']",Int J Mol Sci,,,True
0241ada1b12eaacadc56a59586bc1728a580583d,PMC,Permissiveness of human hepatoma cell lines for HCV infection,http://dx.doi.org/10.1186/1743-422X-9-30,PMC3317838,22273112,CC BY,"BACKGROUND: Although primary and established human hepatoma cell lines have been evaluated for hepatitis C virus (HCV) infection in vitro, thus far only Huh7 cells have been found to be highly permissive for infectious HCV. Since our understanding of the HCV lifecycle would benefit from the identification of additional permissive cell lines, we assembled a panel of hepatic and non-hepatic cell lines and assessed their ability to support HCV infection. Here we show infection of the human hepatoma cell lines PLC/PRF/5 and Hep3B with cell culture-derived HCV (HCVcc), albeit to lower levels than that achieved in Huh7 cells. To better understand the reduced permissiveness of PLC and Hep3B cells for HCVcc infection, we performed studies to evaluate the ability of each cell line to support specific steps of the viral lifecycle (i.e. entry, replication, egress and spread). RESULTS: We found that while the early events in HCV infection (i.e. entry plus replication initiation) are cumulatively equivalent or only marginally reduced in PLC and Hep3B cells, later steps of the viral life cycle such as steady-state replication, de novo virus production and/or spread are impaired to different degrees in PLC and Hep3B cultures compared to Huh7 cell cultures. Interestingly, we also observed that interferon stimulated gene (i.e. ISG56) expression was significantly and differentially up-regulated in PLC and Hep3B cells following viral infection. CONCLUSIONS: We conclude that the restrictions observed later during HCV infection in these cell lines could in part be attributed to HCV-induced innate signaling. Nevertheless, the identification of two new cell lines capable of supporting authentic HCVcc infection, even at reduced levels, expands the current repertoire of cell lines amendable for the study of HCV in vitro and should aid in further elucidating HCV biology and the cellular determinants that modulate HCV infection.",2012 Jan 24,"['Sainz, Bruno', 'Barretto, Naina', 'Yu, Xuemei', 'Corcoran, Peter', 'Uprichard, Susan L']",Virol J,,,True
454a87f362323152fc47fe4593afc755422f1e7b,PMC,Detection of Mycobacterium ulcerans by the Loop Mediated Isothermal Amplification Method,http://dx.doi.org/10.1371/journal.pntd.0001590,PMC3317900,22509415,CC BY,"BACKGROUND: Buruli ulcer (BU) caused by Mycobacterium ulcerans (M. ulcerans) has emerged as an important public health problem in several rural communities in sub-Saharan Africa. Early diagnosis and prompt treatment are important in preventing disfiguring complications associated with late stages of the disease progression. Presently there is no simple and rapid test that is appropriate for early diagnosis and use in the low-resource settings where M. ulcerans is most prevalent. METHODOLOGY: We compared conventional and pocket warmer loop mediated isothermal amplification (LAMP) methods (using a heat block and a pocket warmer respectively as heat source for amplification reaction) for the detection of M. ulcerans in clinical specimens. The effect of purified and crude DNA preparations on the detection rate of the LAMP assays were also investigated and compared with that of IS2404 PCR, a reference assay for the detection of M. ulcerans. Thirty clinical specimens from suspected BU cases were examined by LAMP and IS2404 PCR. PRINCIPAL FINDINGS: The lower detection limit of both LAMP methods at 60°C was 300 copies of IS2404 and 30 copies of IS2404 for the conventional LAMP at 65°C. When purified DNA extracts were used, both the conventional LAMP and IS2404 PCR concordantly detected 21 positive cases, while the pocket warmer LAMP detected 19 cases. Nine of 30 samples were positive by both the LAMP assays as well as IS2404 PCR when crude extracts of clinical specimens were used. CONCLUSION/SIGNIFICANCE: The LAMP method can be used as a simple and rapid test for the detection of M. ulcerans in clinical specimens. However, obtaining purified DNA, as well as generating isothermal conditions, remains a major challenge for the use of the LAMP method under field conditions. With further improvement in DNA extraction and amplification conditions, the pwLAMP could be used as a point of care diagnostic test for BU",2012 Apr 3,"['Ablordey, Anthony', 'Amissah, Diana Ackon', 'Aboagye, Isaac Frimpong', 'Hatano, Ben', 'Yamazaki, Toshio', 'Sata, Tetsutaro', 'Ishikawa, Koichi', 'Katano, Harutaka']",PLoS Negl Trop Dis,,,True
51a9f0de2c657fd582c5ff023027833d48e4876b,PMC,A Human PrM Antibody That Recognizes a Novel Cryptic Epitope on Dengue E Glycoprotein,http://dx.doi.org/10.1371/journal.pone.0033451,PMC3317930,22509258,CC BY,"Dengue virus (DENV) is a major mosquito-borne pathogen infecting up to 100 million people each year; so far no effective treatment or vaccines are available. Recently, highly cross-reactive and infection-enhancing pre-membrane (prM)-specific antibodies were found to dominate the anti-DENV immune response in humans, raising concern over vaccine candidates that contain native dengue prM sequences. In this study, we have isolated a broadly cross-reactive prM-specific antibody, D29, during a screen with a non-immunized human Fab-phage library against the four serotypes of DENV. The antibody is capable of restoring the infectivity of virtually non-infectious immature DENV (imDENV) in FcγR-bearing K562 cells. Remarkably, D29 also cross-reacted with a cryptic epitope on the envelope (E) protein located to the DI/DII junction as evidenced by site-directed mutagenesis. This cryptic epitope, while inaccessible to antibody binding in a native virus particle, may become exposed if E is not properly folded. These findings suggest that generation of anti-prM antibodies that enhance DENV infection may not be completely avoided even with immunization strategies employing E protein alone or subunits of E proteins.",2012 Apr 3,"['Chan, Annie Hoi Yi', 'Tan, Hwee Cheng', 'Chow, Angelia Yee', 'Lim, Angeline Pei Chiew', 'Lok, Shee Mei', 'Moreland, Nicole J.', 'Vasudevan, Subhash G.', 'MacAry, Paul A.', 'Ooi, Eng Eong', 'Hanson, Brendon J.']",PLoS One,,,True
6b51562f63de5739f2b7ebf5f9c34365ac6ee545,PMC,A Non-VH1-69 Heterosubtypic Neutralizing Human Monoclonal Antibody Protects Mice against H1N1 and H5N1 Viruses,http://dx.doi.org/10.1371/journal.pone.0034415,PMC3319592,22496802,CC0,"Influenza viruses are among the most important human pathogens and are responsible for annual epidemics and sporadic, potentially devastating pandemics. The humoral immune response plays an important role in the defense against these viruses, providing protection mainly by producing antibodies directed against the hemagglutinin (HA) glycoprotein. However, their high genetic variability allows the virus to evade the host immune response and the potential protection offered by seasonal vaccines. The emergence of resistance to antiviral drugs in recent years further limits the options available for the control of influenza. The development of alternative strategies for influenza prophylaxis and therapy is therefore urgently needed. In this study, we describe a human monoclonal antibody (PN-SIA49) that recognizes a highly conserved epitope located on the stem region of the HA and able to neutralize a broad spectrum of influenza viruses belonging to different subtypes (H1, H2 and H5). Furthermore, we describe its protective activity in mice after lethal challenge with H1N1 and H5N1 viruses suggesting a potential application in the treatment of influenza virus infections.",2012 Apr 4,"['De Marco, Donata', 'Clementi, Nicola', 'Mancini, Nicasio', 'Solforosi, Laura', 'Moreno, Guisella J.', 'Sun, Xiangjie', 'Tumpey, Terrence M.', 'Gubareva, Larisa V.', 'Mishin, Vasiliy', 'Clementi, Massimo', 'Burioni, Roberto']",PLoS One,,,True
1fbbc167a21646cce197832a514a0877f0846fb4,PMC,A Non-VH1-69 Heterosubtypic Neutralizing Human Monoclonal Antibody Protects Mice against H1N1 and H5N1 Viruses,http://dx.doi.org/10.1371/journal.pone.0034415,PMC3319592,22496802,CC0,"Influenza viruses are among the most important human pathogens and are responsible for annual epidemics and sporadic, potentially devastating pandemics. The humoral immune response plays an important role in the defense against these viruses, providing protection mainly by producing antibodies directed against the hemagglutinin (HA) glycoprotein. However, their high genetic variability allows the virus to evade the host immune response and the potential protection offered by seasonal vaccines. The emergence of resistance to antiviral drugs in recent years further limits the options available for the control of influenza. The development of alternative strategies for influenza prophylaxis and therapy is therefore urgently needed. In this study, we describe a human monoclonal antibody (PN-SIA49) that recognizes a highly conserved epitope located on the stem region of the HA and able to neutralize a broad spectrum of influenza viruses belonging to different subtypes (H1, H2 and H5). Furthermore, we describe its protective activity in mice after lethal challenge with H1N1 and H5N1 viruses suggesting a potential application in the treatment of influenza virus infections.",2012 Apr 4,"['De Marco, Donata', 'Clementi, Nicola', 'Mancini, Nicasio', 'Solforosi, Laura', 'Moreno, Guisella J.', 'Sun, Xiangjie', 'Tumpey, Terrence M.', 'Gubareva, Larisa V.', 'Mishin, Vasiliy', 'Clementi, Massimo', 'Burioni, Roberto']",PLoS One,,,False
dda03cf2660471cfbde21ca13001cfe145c8801b,PMC,A Non-VH1-69 Heterosubtypic Neutralizing Human Monoclonal Antibody Protects Mice against H1N1 and H5N1 Viruses,http://dx.doi.org/10.1371/journal.pone.0034415,PMC3319592,22496802,CC0,"Influenza viruses are among the most important human pathogens and are responsible for annual epidemics and sporadic, potentially devastating pandemics. The humoral immune response plays an important role in the defense against these viruses, providing protection mainly by producing antibodies directed against the hemagglutinin (HA) glycoprotein. However, their high genetic variability allows the virus to evade the host immune response and the potential protection offered by seasonal vaccines. The emergence of resistance to antiviral drugs in recent years further limits the options available for the control of influenza. The development of alternative strategies for influenza prophylaxis and therapy is therefore urgently needed. In this study, we describe a human monoclonal antibody (PN-SIA49) that recognizes a highly conserved epitope located on the stem region of the HA and able to neutralize a broad spectrum of influenza viruses belonging to different subtypes (H1, H2 and H5). Furthermore, we describe its protective activity in mice after lethal challenge with H1N1 and H5N1 viruses suggesting a potential application in the treatment of influenza virus infections.",2012 Apr 4,"['De Marco, Donata', 'Clementi, Nicola', 'Mancini, Nicasio', 'Solforosi, Laura', 'Moreno, Guisella J.', 'Sun, Xiangjie', 'Tumpey, Terrence M.', 'Gubareva, Larisa V.', 'Mishin, Vasiliy', 'Clementi, Massimo', 'Burioni, Roberto']",PLoS One,,,False
2ab8cb240c2f488f5a7bbcf117239eed7e3b9633,PMC,A Non-VH1-69 Heterosubtypic Neutralizing Human Monoclonal Antibody Protects Mice against H1N1 and H5N1 Viruses,http://dx.doi.org/10.1371/journal.pone.0034415,PMC3319592,22496802,CC0,"Influenza viruses are among the most important human pathogens and are responsible for annual epidemics and sporadic, potentially devastating pandemics. The humoral immune response plays an important role in the defense against these viruses, providing protection mainly by producing antibodies directed against the hemagglutinin (HA) glycoprotein. However, their high genetic variability allows the virus to evade the host immune response and the potential protection offered by seasonal vaccines. The emergence of resistance to antiviral drugs in recent years further limits the options available for the control of influenza. The development of alternative strategies for influenza prophylaxis and therapy is therefore urgently needed. In this study, we describe a human monoclonal antibody (PN-SIA49) that recognizes a highly conserved epitope located on the stem region of the HA and able to neutralize a broad spectrum of influenza viruses belonging to different subtypes (H1, H2 and H5). Furthermore, we describe its protective activity in mice after lethal challenge with H1N1 and H5N1 viruses suggesting a potential application in the treatment of influenza virus infections.",2012 Apr 4,"['De Marco, Donata', 'Clementi, Nicola', 'Mancini, Nicasio', 'Solforosi, Laura', 'Moreno, Guisella J.', 'Sun, Xiangjie', 'Tumpey, Terrence M.', 'Gubareva, Larisa V.', 'Mishin, Vasiliy', 'Clementi, Massimo', 'Burioni, Roberto']",PLoS One,,,False
9575b82e4a705536bb73124514fa77255c3467c2,PMC,A Non-VH1-69 Heterosubtypic Neutralizing Human Monoclonal Antibody Protects Mice against H1N1 and H5N1 Viruses,http://dx.doi.org/10.1371/journal.pone.0034415,PMC3319592,22496802,CC0,"Influenza viruses are among the most important human pathogens and are responsible for annual epidemics and sporadic, potentially devastating pandemics. The humoral immune response plays an important role in the defense against these viruses, providing protection mainly by producing antibodies directed against the hemagglutinin (HA) glycoprotein. However, their high genetic variability allows the virus to evade the host immune response and the potential protection offered by seasonal vaccines. The emergence of resistance to antiviral drugs in recent years further limits the options available for the control of influenza. The development of alternative strategies for influenza prophylaxis and therapy is therefore urgently needed. In this study, we describe a human monoclonal antibody (PN-SIA49) that recognizes a highly conserved epitope located on the stem region of the HA and able to neutralize a broad spectrum of influenza viruses belonging to different subtypes (H1, H2 and H5). Furthermore, we describe its protective activity in mice after lethal challenge with H1N1 and H5N1 viruses suggesting a potential application in the treatment of influenza virus infections.",2012 Apr 4,"['De Marco, Donata', 'Clementi, Nicola', 'Mancini, Nicasio', 'Solforosi, Laura', 'Moreno, Guisella J.', 'Sun, Xiangjie', 'Tumpey, Terrence M.', 'Gubareva, Larisa V.', 'Mishin, Vasiliy', 'Clementi, Massimo', 'Burioni, Roberto']",PLoS One,,,False
7b4b3759cdde4218ea23a081b386bcffd7e6afc6,PMC,A Family-Wide RT-PCR Assay for Detection of Paramyxoviruses and Application to a Large-Scale Surveillance Study,http://dx.doi.org/10.1371/journal.pone.0034961,PMC3319594,22496880,CC BY,"Family-wide molecular diagnostic assays are valuable tools for initial identification of viruses during outbreaks and to limit costs of surveillance studies. Recent discoveries of paramyxoviruses have called for such assay that is able to detect all known and unknown paramyxoviruses in one round of PCR amplification. We have developed a RT-PCR assay consisting of a single degenerate primer set, able to detect all members of the Paramyxoviridae family including all virus genera within the subfamilies Paramyxovirinae and Pneumovirinae. Primers anneal to domain III of the polymerase gene, with the 3′ end of the reverse primer annealing to the conserved motif GDNQ, which is proposed to be the active site for nucleotide polymerization. The assay was fully optimized and was shown to indeed detect all available paramyxoviruses tested. Clinical specimens from hospitalized patients that tested positive for known paramyxoviruses in conventional assays were also detected with the novel family-wide test. A high-throughput fluorescence-based RT-PCR version of the assay was developed for screening large numbers of specimens. A large number of samples collected from wild birds was tested, resulting in the detection of avian paramyxoviruses type 1 in both barnacle and white-fronted geese, and type 8 in barnacle geese. Avian metapneumovirus type C was found for the first time in Europe in mallards, greylag geese and common gulls. The single round family-wide RT-PCR assay described here is a useful tool for the detection of known and unknown paramyxoviruses, and screening of large sample collections from humans and animals.",2012 Apr 4,"['van Boheemen, Sander', 'Bestebroer, Theo M.', 'Verhagen, Josanne H.', 'Osterhaus, Albert D. M. E.', 'Pas, Suzan D.', 'Herfst, Sander', 'Fouchier, Ron A. M.']",PLoS One,,,True
0b9b177210a4b23ff4745f2717083ba047a9e770,PMC,Systematic Identification of Spontaneous Preterm Birth-Associated RNA Transcripts in Maternal Plasma,http://dx.doi.org/10.1371/journal.pone.0034328,PMC3320630,22496790,CC BY,"BACKGROUND: Spontaneous preterm birth (SPB, before 37 gestational weeks) is a major cause of perinatal mortality and morbidity, but its pathogenesis remains unclear. Studies on SPB have been hampered by the limited availability of markers for SPB in predelivery clinical samples that can be easily compared with gestational age-matched normal controls. We hypothesize that SPB involves aberrant placental RNA expression, and that such RNA transcripts can be detected in predelivery maternal plasma samples, which can be compared with gestational age-matched controls. PRINCIPAL FINDINGS: Using gene expression microarray to profile essentially all human genes, we observed that 426 probe signals were changed by >2.9-fold in the SPB placentas, compared with the spontaneous term birth (STB) placentas. Among the genes represented by those probes, we observed an over-representation of functions in RNA stabilization, extracellular matrix binding, and acute inflammatory response. Using RT-quantitative PCR, we observed differences in the RNA concentrations of certain genes only between the SPB and STB placentas, but not between the STB and term elective cesarean delivery placentas. Notably, 36 RNA transcripts were observed at placental microarray signals higher than a threshold, which indicated the possibility of their detection in maternal plasma. Among them, the IL1RL1 mRNA was tested in plasma samples taken from 37 women. It was detected in 6 of 10 (60%) plasma samples collected during the presentation of preterm labor (≤32.9 weeks) in women eventually giving SPB, but was detected in only 1 of 27 (4%) samples collected during matched gestational weeks from women with no preterm labor (Fisher exact test, p = 0.00056). CONCLUSION: We have identified 36 SPB-associated RNA transcripts, which are possibly detectable in maternal plasma. We have illustrated that the IL1RL1 mRNA was more frequently detected in predelivery maternal plasma samples collected from women resulting in SPB than the gestational-age matched controls.",2012 Apr 5,"['Chim, Stephen S. C.', 'Lee, Wing S.', 'Ting, Yuen H.', 'Chan, Oi K.', 'Lee, Shara W. Y.', 'Leung, Tak Y.']",PLoS One,,,True
23f5f98892b12255b20f4b0a0ec1f3e7b29d5d72,PMC,Angiotensin-Converting Enzyme 2 (ACE2) Is a Key Modulator of the Renin Angiotensin System in Health and Disease,http://dx.doi.org/10.1155/2012/256294,PMC3321295,22536270,CC BY,"Angiotensin-converting enzyme 2 (ACE2) shares some homology with angiotensin-converting enzyme (ACE) but is not inhibited by ACE inhibitors. The main role of ACE2 is the degradation of Ang II resulting in the formation of angiotensin 1–7 (Ang 1–7) which opposes the actions of Ang II. Increased Ang II levels are thought to upregulate ACE2 activity, and in ACE2 deficient mice Ang II levels are approximately double that of wild-type mice, whilst Ang 1–7 levels are almost undetectable. Thus, ACE2 plays a crucial role in the RAS because it opposes the actions of Ang II. Consequently, it has a beneficial role in many diseases such as hypertension, diabetes, and cardiovascular disease where its expression is decreased. Not surprisingly, current therapeutic strategies for ACE2 involve augmenting its expression using ACE2 adenoviruses, recombinant ACE2 or compounds in these diseases thereby affording some organ protection.",2012 Mar 20,"['Tikellis, Chris', 'Thomas, M. C.']",Int J Pept,,,True
084f1464fd6c0885f64af9c09c1460ef50dddd01,PMC,Revealing −1 Programmed Ribosomal Frameshifting Mechanisms by Single-Molecule Techniques and Computational Methods,http://dx.doi.org/10.1155/2012/569870,PMC3321566,22545064,CC BY,"Programmed ribosomal frameshifting (PRF) serves as an intrinsic translational regulation mechanism employed by some viruses to control the ratio between structural and enzymatic proteins. Most viral mRNAs which use PRF adapt an H-type pseudoknot to stimulate −1 PRF. The relationship between the thermodynamic stability and the frameshifting efficiency of pseudoknots has not been fully understood. Recently, single-molecule force spectroscopy has revealed that the frequency of −1 PRF correlates with the unwinding forces required for disrupting pseudoknots, and that some of the unwinding work dissipates irreversibly due to the torsional restraint of pseudoknots. Complementary to single-molecule techniques, computational modeling provides insights into global motions of the ribosome, whose structural transitions during frameshifting have not yet been elucidated in atomic detail. Taken together, recent advances in biophysical tools may help to develop antiviral therapies that target the ubiquitous −1 PRF mechanism among viruses.",2012 Apr 1,"Chang, Kai-Chun",Comput Math Methods Med,,,True
6ea0187c80591fcbe19d37343f9957859753b129,PMC,Human Cytomegalovirus Entry into Dendritic Cells Occurs via a Macropinocytosis-Like Pathway in a pH-Independent and Cholesterol-Dependent Manner,http://dx.doi.org/10.1371/journal.pone.0034795,PMC3322158,22496863,CC BY,"Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that is able to infect fibroblastic, epithelial, endothelial and hematopoietic cells. Over the past ten years, several groups have provided direct evidence that dendritic cells (DCs) fully support the HCMV lytic cycle. We previously demonstrated that the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) has a prominent role in the docking of HCMV on monocyte-derived DCs (MDDCs). The DC-SIGN/HCMV interaction was demonstrated to be a crucial and early event that substantially enhanced infection in trans, i.e., from one CMV-bearing cell to another non-infected cell (or trans-infection), and rendered susceptible cells fully permissive to HCMV infection. Nevertheless, nothing is yet known about how HCMV enters MDDCs. In this study, we demonstrated that VHL/E HCMV virions (an endothelio/dendrotropic strain) are first internalized into MDDCs by a macropinocytosis-like process in an actin- and cholesterol-dependent, but pH-independent, manner. We observed the accumulation of virions in large uncoated vesicles with endosomal features, and the virions remained as intact particles that retained infectious potential for several hours. This trans-infection property was specific to MDDCs because monocyte-derived macrophages or monocytes from the same donor were unable to allow the accumulation of and the subsequent transmission of the virus. Together, these data allowed us to delineate the early mechanisms of the internalization and entry of an endothelio/dendrotropic HCMV strain into human MDDCs and to propose that DCs can serve as a ""Trojan horse"" to convey CMV from entry sites to other locations that may favor the occurrence of either latency or acute infection.",2012 Apr 9,"['Haspot, Fabienne', 'Lavault, Amélie', 'Sinzger, Christian', 'Laib Sampaio, Kerstin', 'Stierhof, York-Dieter', 'Pilet, Paul', 'Bressolette-Bodin, Céline', 'Halary, Franck']",PLoS One,,,True
24ed22a878649ce74463bf63090563093d002c86,PMC,Exposure to Ozone Modulates Human Airway Protease/Antiprotease Balance Contributing to Increased Influenza A Infection,http://dx.doi.org/10.1371/journal.pone.0035108,PMC3322171,22496898,CC BY,"Exposure to oxidant air pollution is associated with increased respiratory morbidities and susceptibility to infections. Ozone is a commonly encountered oxidant air pollutant, yet its effects on influenza infections in humans are not known. The greater Mexico City area was the primary site for the spring 2009 influenza A H1N1 pandemic, which also coincided with high levels of environmental ozone. Proteolytic cleavage of the viral membrane protein hemagglutinin (HA) is essential for influenza virus infectivity. Recent studies suggest that HA cleavage might be cell-associated and facilitated by the type II transmembrane serine proteases (TTSPs) human airway trypsin-like protease (HAT) and transmembrane protease, serine 2 (TMPRSS2), whose activities are regulated by antiproteases, such as secretory leukocyte protease inhibitor (SLPI). Based on these observations, we sought to determine how acute exposure to ozone may modulate cellular protease/antiprotease expression and function, and to define their roles in a viral infection. We utilized our in vitro model of differentiated human nasal epithelial cells (NECs) to determine the effects of ozone on influenza cleavage, entry, and replication. We show that ozone exposure disrupts the protease/antiprotease balance within the airway liquid. We also determined that functional forms of HAT, TMPRSS2, and SLPI are secreted from human airway epithelium, and acute exposure to ozone inversely alters their expression levels. We also show that addition of antioxidants significantly reduces virus replication through the induction of SLPI. In addition, we determined that ozone-induced cleavage of the viral HA protein is not cell-associated and that secreted endogenous proteases are sufficient to activate HA leading to a significant increase in viral replication. Our data indicate that pre-exposure to ozone disrupts the protease/antiprotease balance found in the human airway, leading to increased influenza susceptibility.",2012 Apr 9,"['Kesic, Matthew J.', 'Meyer, Megan', 'Bauer, Rebecca', 'Jaspers, Ilona']",PLoS One,,,True
5e01fabcf9b38073be541d0ac1c9f147c99a7af7,PMC,Predicting RNA-Protein Interactions Using Only Sequence Information,http://dx.doi.org/10.1186/1471-2105-12-489,PMC3322362,22192482,CC BY,"BACKGROUND: RNA-protein interactions (RPIs) play important roles in a wide variety of cellular processes, ranging from transcriptional and post-transcriptional regulation of gene expression to host defense against pathogens. High throughput experiments to identify RNA-protein interactions are beginning to provide valuable information about the complexity of RNA-protein interaction networks, but are expensive and time consuming. Hence, there is a need for reliable computational methods for predicting RNA-protein interactions. RESULTS: We propose RPISeq, a family of classifiers for predicting RNA-protein interactions using only sequence information. Given the sequences of an RNA and a protein as input, RPIseq predicts whether or not the RNA-protein pair interact. The RNA sequence is encoded as a normalized vector of its ribonucleotide 4-mer composition, and the protein sequence is encoded as a normalized vector of its 3-mer composition, based on a 7-letter reduced alphabet representation. Two variants of RPISeq are presented: RPISeq-SVM, which uses a Support Vector Machine (SVM) classifier and RPISeq-RF, which uses a Random Forest classifier. On two non-redundant benchmark datasets extracted from the Protein-RNA Interface Database (PRIDB), RPISeq achieved an AUC (Area Under the Receiver Operating Characteristic (ROC) curve) of 0.96 and 0.92. On a third dataset containing only mRNA-protein interactions, the performance of RPISeq was competitive with that of a published method that requires information regarding many different features (e.g., mRNA half-life, GO annotations) of the putative RNA and protein partners. In addition, RPISeq classifiers trained using the PRIDB data correctly predicted the majority (57-99%) of non-coding RNA-protein interactions in NPInter-derived networks from E. coli, S. cerevisiae, D. melanogaster, M. musculus, and H. sapiens. CONCLUSIONS: Our experiments with RPISeq demonstrate that RNA-protein interactions can be reliably predicted using only sequence-derived information. RPISeq offers an inexpensive method for computational construction of RNA-protein interaction networks, and should provide useful insights into the function of non-coding RNAs. RPISeq is freely available as a web-based server at http://pridb.gdcb.iastate.edu/RPISeq/.",2011 Dec 22,"['Muppirala, Usha K', 'Honavar, Vasant G', 'Dobbs, Drena']",BMC Bioinformatics,,,True
a50f2af4833bd314b5664e5f30a6d39792a73f5c,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,True
2c5d92ede870cbdc9d8e4b5544544c731125bc5d,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,False
de15170cb79d459586be28d687e7d68117990644,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,True
7f33a63936788ad95efb0f3d3fa1c972467b834c,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,False
a3de313c4235416a3a155a4bf154221a068ba051,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,False
ade49137a1c6f7c78b0330d906c56d7dafe52ffe,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,False
0bca7d5c8cbaf92b1d7e86518f0b42680522238a,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,False
7d2c7c6c8de76b497f0b8a4aa354f6a00b0c4854,PMC,Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone,http://dx.doi.org/10.1371/journal.pcbi.1002454,PMC3325179,22511854,CC BY,"An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.",2012 Apr 12,"['Cooper, Ben S.', 'Kypraios, Theodore', 'Batra, Rahul', 'Wyncoll, Duncan', 'Tosas, Olga', 'Edgeworth, Jonathan D.']",PLoS Comput Biol,,,False
6c9c09c364d2fbd8d8f319029e60693060b6c756,PMC,A Caprine Herpesvirus 1 Vaccine Adjuvanted with MF59™ Protects against Vaginal Infection and Interferes with the Establishment of Latency in Goats,http://dx.doi.org/10.1371/journal.pone.0034913,PMC3325274,22511971,CC BY,"The immunogenicity and the efficacy of a beta-propiolactone-inactivated caprine herpesvirus 1 (CpHV-1) vaccine adjuvanted with MF59™ were tested in goats. Following two subcutaneous immunizations, goats developed high titers of CpHV-1-specific serum and vaginal IgG and high serum virus neutralization (VN) titers. Peripheral blood mononuclear cells (PBMC) stimulated in vitro with inactivated CpHV-1 produced high levels of soluble IFN-gamma and exhibited high frequencies of IFN-gamma producing cells while soluble IL-4 was undetectable. On the other hand, control goats receiving the inactivated CpHV-1 vaccine without adjuvant produced only low serum antibody responses. A vaginal challenge with virulent CpHV-1 was performed in all vaccinated goats and in naïve goats to assess the efficacy of the two vaccines. Vaginal disease was not detected in goats vaccinated with inactivated CpHV-1 plus MF59™ and these animals had undetectable levels of infectious challenge virus in their vaginal washes. Goats vaccinated with inactivated CpHV-1 in the absence of adjuvant exhibited a less severe disease when compared to naïve goats but shed titers of challenge virus that were similar to those of naïve goats. Detection and quantitation of latent CpHV-1 DNA in sacral ganglia in challenged goats revealed that the inactivated CpHV-1 plus MF59™ vaccine was able to significantly reduce the latent viral load when compared either to the naïve goats or to the goats vaccinated with inactivated CpHV-1 in the absence of adjuvant. Thus, a vaccine composed of inactivated CpHV-1 plus MF59™ as adjuvant was strongly immunogenic and induced effective immunity against vaginal CpHV-1 infection in goats.",2012 Apr 12,"['Marinaro, Mariarosaria', 'Rezza, Giovanni', 'Del Giudice, Giuseppe', 'Colao, Valeriana', 'Tarsitano, Elvira', 'Camero, Michele', 'Losurdo, Michele', 'Buonavoglia, Canio', 'Tempesta, Maria']",PLoS One,,,True
dbf7ea2d45fff41a73853c26e5fca9862fd0edcc,PMC,Discovery and Genomic Characterization of a Novel Bat Sapovirus with Unusual Genomic Features and Phylogenetic Position,http://dx.doi.org/10.1371/journal.pone.0034987,PMC3325917,22514697,CC BY,"Sapovirus is a genus of caliciviruses that are known to cause enteric disease in humans and animals. There is considerable genetic diversity among the sapoviruses, which are classified into different genogroups based on phylogenetic analysis of the full-length capsid protein sequence. While several mammalian species, including humans, pigs, minks, and dogs, have been identified as animal hosts for sapoviruses, there were no reports of sapoviruses in bats in spite of their biological diversity. In this report, we present the results of a targeted surveillance study in different bat species in Hong Kong. Five of the 321 specimens from the bat species, Hipposideros pomona, were found to be positive for sapoviruses by RT-PCR. Complete or nearly full-length genome sequences of approximately 7.7 kb in length were obtained for three strains, which showed similar organization of the genome compared to other sapoviruses. Interestingly, they possess many genomic features atypical of most sapoviruses, like high G+C content and minimal CpG suppression. Phylogenetic analysis of the viral proteins suggested that the bat sapovirus descended from an ancestral sapovirus lineage and is most closely related to the porcine sapoviruses. Codon usage analysis showed that the bat sapovirus genome has greater codon usage bias relative to other sapovirus genomes. In summary, we report the discovery and genomic characterization of the first bat calicivirus, which appears to have evolved under different conditions after early divergence from other sapovirus lineages.",2012 Apr 13,"['Tse, Herman', 'Chan, Wan-Mui', 'Li, Kenneth S. M.', 'Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung']",PLoS One,,,True
945a7da3231e06eeb8a4a39471338e279c2e6f28,PMC,Simultaneous Identification of DNA and RNA Viruses Present in Pig Faeces Using Process-Controlled Deep Sequencing,http://dx.doi.org/10.1371/journal.pone.0034631,PMC3326065,22514648,CC BY,"BACKGROUND: Animal faeces comprise a community of many different microorganisms including bacteria and viruses. Only scarce information is available about the diversity of viruses present in the faeces of pigs. Here we describe a protocol, which was optimized for the purification of the total fraction of viral particles from pig faeces. The genomes of the purified DNA and RNA viruses were simultaneously amplified by PCR and subjected to deep sequencing followed by bioinformatic analyses. The efficiency of the method was monitored using a process control consisting of three bacteriophages (T4, M13 and MS2) with different morphology and genome types. Defined amounts of the bacteriophages were added to the sample and their abundance was assessed by quantitative PCR during the preparation procedure. RESULTS: The procedure was applied to a pooled faecal sample of five pigs. From this sample, 69,613 sequence reads were generated. All of the added bacteriophages were identified by sequence analysis of the reads. In total, 7.7% of the reads showed significant sequence identities with published viral sequences. They mainly originated from bacteriophages (73.9%) and mammalian viruses (23.9%); 0.8% of the sequences showed identities to plant viruses. The most abundant detected porcine viruses were kobuvirus, rotavirus C, astrovirus, enterovirus B, sapovirus and picobirnavirus. In addition, sequences with identities to the chimpanzee stool-associated circular ssDNA virus were identified. Whole genome analysis indicates that this virus, tentatively designated as pig stool-associated circular ssDNA virus (PigSCV), represents a novel pig virus. CONCLUSION: The established protocol enables the simultaneous detection of DNA and RNA viruses in pig faeces including the identification of so far unknown viruses. It may be applied in studies investigating aetiology, epidemiology and ecology of diseases. The implemented process control serves as quality control, ensures comparability of the method and may be used for further method optimization.",2012 Apr 13,"['Sachsenröder, Jana', 'Twardziok, Sven', 'Hammerl, Jens A.', 'Janczyk, Pawel', 'Wrede, Paul', 'Hertwig, Stefan', 'Johne, Reimar']",PLoS One,,,True
18a116d870bd24c96d95317418946ce0873f2180,PMC,Ocular pathogenesis and immune reaction after intravitreal dispase injection in mice,,PMC3327440,22511850,CC BY,"PURPOSE: The purpose of the current study was to examine the ocular pathogenesis and immune reaction in mice after intravitreal dispase injection. METHODS: Three microliters of dispase at a concentration of 0.2 U/μl were injected into the vitreal cavities of 4–6-week-old mice. Hematoxylin and eosin staining, immunofluorescence analysis, and electroretinograms of the eyes were then performed to assess ocular changes, and enzyme-linked immunospot assays and intracellular staining of single-cell suspensions of the spleens were used to detect immune changes during an 8 week observation period. RESULTS: Neutrophils were the main inflammatory infiltrating cells appearing at the anterior chamber. No cluster of differentiation (CD)3+ labeled T cells, F4/80+ labeled macrophages, or CD56+ labeled natural killer cells were found in the vitreal cavities or retinas in dispase-injected mice within 5 days after injection. Proliferative vitreoretinopathy (PVR)-like signs first appeared at 2 weeks, gradually increased thereafter, and reached peak values at 8 weeks. There was a statistically significant difference in b-wave amplitudes between the PVR and saline-control eyes. Enzyme-linked immunospot assays and intracellular staining showed that specific CD4+ and CD8+ labeled T cells were not involved in dispase-injected mice. CONCLUSIONS: Our data show that neutrophils in the anterior chamber and PVR-like signs in the retinas were found, and that specific immune reactions were not involved after intravitreal dispase injection in mice.",2012 Apr 7,"['Tan, Juan', 'Liu, Yaqin', 'Li, Wei', 'Gao, Qianying']",Mol Vis,,,True
267084b4bdfd4a3d8fbdb8d7e4c935715f3e7171,PMC,Angiotensin Converting Enzyme (ACE) and ACE2 Bind Integrins and ACE2 Regulates Integrin Signalling,http://dx.doi.org/10.1371/journal.pone.0034747,PMC3327712,22523556,CC BY,"The angiotensin converting enzymes (ACEs) are the key catalytic components of the renin-angiotensin system, mediating precise regulation of blood pressure by counterbalancing the effects of each other. Inhibition of ACE has been shown to improve pathology in cardiovascular disease, whilst ACE2 is cardioprotective in the failing heart. However, the mechanisms by which ACE2 mediates its cardioprotective functions have yet to be fully elucidated. Here we demonstrate that both ACE and ACE2 bind integrin subunits, in an RGD-independent manner, and that they can act as cell adhesion substrates. We show that cellular expression of ACE2 enhanced cell adhesion. Furthermore, we present evidence that soluble ACE2 (sACE2) is capable of suppressing integrin signalling mediated by FAK. In addition, sACE2 increases the expression of Akt, thereby lowering the proportion of the signalling molecule phosphorylated Akt. These results suggest that ACE2 plays a role in cell-cell interactions, possibly acting to fine-tune integrin signalling. Hence the expression and cleavage of ACE2 at the plasma membrane may influence cell-extracellular matrix interactions and the signalling that mediates cell survival and proliferation. As such, ectodomain shedding of ACE2 may play a role in the process of pathological cardiac remodelling.",2012 Apr 16,"['Clarke, Nicola E.', 'Fisher, Martin J.', 'Porter, Karen E.', 'Lambert, Daniel W.', 'Turner, Anthony J.']",PLoS One,,,True
83d77dc0616b9b240d13a844c7135dc250773fe0,PMC,Altered Thymic Function during Interferon Therapy in HCV-Infected Patients,http://dx.doi.org/10.1371/journal.pone.0034326,PMC3328332,22529911,CC BY,"Interferon alpha (IFNα) therapy, despite good efficacy in curing HCV infection, leads to major side effects, in particular inducement of a strong peripheral T-cell lymphocytopenia. We here analyze the early consequences of IFNα therapy on both thymic function and peripheral T-cell homeostasis in patients in the acute or chronic phase of HCV-infection as well as in HIV/HCV co-infected patients. The evolution of T-cell subsets and T-cell homeostasis were estimated by flow cytometry while thymic function was measured through quantification of T-cell receptor excision circles (TREC) and estimation of intrathymic precursor T-cell proliferation during the first four months following the initiation of IFNα therapy. Beginning with the first month of therapy, a profound lymphocytopenia was observed for all T-cell subsets, including naïve T-cells and recent thymic emigrants (RTE), associated with inhibition of intrathymic precursor T-cell proliferation. Interleukin (IL)-7 plasma concentration rapidly dropped while lymphocytopenia progressed. This was neither a consequence of higher consumption of the cytokine nor due to its neutralization by soluble CD127. Decrease in IL-7 plasma concentration under IFNα therapy correlated with the decline in HCV viral load, thymic activity and RTE concentration in blood. These data demonstrate that IFNα-based therapy rapidly impacts on thymopoiesis and, consequently, perturbs T-cell homeostasis. Such a side effect might be detrimental for the continuation of IFNα therapy and may lead to an increased level of infectious risk, in particular in HIV/HCV co-infected patients. Altogether, this study suggests the therapeutic potential of IL-7 in the maintenance of peripheral T-cell homeostasis in IFNα-treated patients.",2012 Apr 16,"['Beq, Stephanie', 'Rozlan, Sandra', 'Pelletier, Sandy', 'Willems, Bernard', 'Bruneau, Julie', 'Lelievre, Jean-Daniel', 'Levy, Yves', 'Shoukry, Naglaa H.', 'Cheynier, Rémi']",PLoS One,,,True
f5edded3536428635cad1f78fe6dc38002690a43,PMC,Current Situation and Perspectives of Clinical Study in Integrative Medicine in China,http://dx.doi.org/10.1155/2012/268542,PMC3328953,22550539,CC BY,"Integrative medicine is not only an innovative China model in clinical practice, but also the bridge for TCM toward the world. In the past thirty years, great achievements have been made in integrative medicine researches, especially in clinical practice. The clinical achievements mainly include the following three: innovating methodology of disease-syndrome combination, excavating the classical theory in traditional Chinese medicine (TCM), preventing and curing refractory diseases. The development ideas and strategies of integrative medicine for future mainly include (a) standing on frontier field of international medicine and improving the capability of preventing and curing refractory diseases; (b) moving prevention and control strategy forward and improving the curative effect of common and frequent disease; (c) excavating the classical theory of TCM and broadening the treatment system of modern medicine; (d) improving the innovation level of new high effective drugs on the basis of classical prescriptions and herbs in TCM; (e) rerecognizing the theory of formula corresponding to syndrome in TCM and enhancing the level of clinical research evidence based on evidence-based medicine. Integrative medicine will do obtain greater achievements in creating new medicine and pharmacology and make more tremendous contributions for the great rejuvenation of the Chinese nation and human health care.",2012 Feb 21,"['Wang, Jie', 'Xiong, Xingjiang']",Evid Based Complement Alternat Med,,,True
c9653d4f2d22837f98e2be157df9dd6516c1ec96,PMC,Pathogenesis and Tissue Distribution of Avian Infectious Bronchitis Virus Isolate IRFIBV32 (793/B Serotype) in Experimentally Infected Broiler Chickens,http://dx.doi.org/10.1100/2012/402537,PMC3329954,22566769,CC BY,"Infectious bronchitis (IB) is one of the most important viral diseases of poultry. The aim of this study was to investigate the distribution of avian infectious bronchitis virus isolate IRFIBV32 (793/B serotype) in experimentally infected chicken. Ninety-one-day-old commercial broilers were divided randomly into two groups (seventy in the experimental and twenty in the control group). Chicks in the experimental group were inoculated intranasally with 10(5) ELD50/0.1 mL of the virus at three weeks of age. The samples from various tissues were collected at1, 2, 3, 5, 7, 11, 13, 15, and 20 days postinoculation. Chickens exhibited mild respiratory signs and depression. Viral RNA was detected in the kidney, lung and tracheas on days 1 to 13 PI, in the oviduct between, days 3 and 13, in testes between days 1 and 11 PI, and in the caecal tonsil consistently up to day 20 PI. The most remarkable clinical signs and virus detection appeared on day 1 PI. Data indicated that the number of infected chickens and viral RNA detection from tissues was reduced with increasing antibody titer on day 20 PI. The results demonstrated that the IRFIBV32 virus has wide tissue distribution for respiratory, urogenital, and digestive systems.",2012 Apr 1,"['Boroomand, Zahra', 'Asasi, Keramat', 'Mohammadi, Ali']",ScientificWorldJournal,,,True
b82539a18c6aea935321822f2de5937fd7fef769,PMC,Pandemic 2009 H1N1 virus infection in children and adults: A cohort study at a single hospital throughout the epidemic,http://dx.doi.org/10.1186/1755-7682-5-13,PMC3331808,22443897,CC BY,"BACKGROUND: In 2009, there was an influenza pandemic in South Korea. The aim of this study was to evaluate the epidemiological, clinical and laboratory characteristics of this infection in children and adults. METHODS: We evaluated the epidemiologic characteristics of patients infected with the 2009 H1N1 influenza A virus (4,463 patients, age range from 2 mo to 86 y), and the clinical and laboratory findings of 373 inpatients (80/217 children, ≤ 15 y, had pneumonia and 36/156 adults, > 16 y, had pneumonia) in a single hospital during the epidemic. RESULTS: The majority of infected patients (94%) were less than 40 y, and greater than 90% of cases occurred during a two-month period. The rates of admission and pneumonia were 8.4% (373/4,463) and 2.5% (116/4,463), respectively. The rates of admission and pneumonia, total duration of fever, the frequency of underlying diseases, and the values of C-reactive protein and erythrocyte sedimentation rate tended to increase as age increased; highest rates were found in the ≥ 65 y group. Pneumonia was founded more boys than girls in children, but more female than male in adults. The adult patients with pneumonia had higher leukocyte counts with lower lymphocyte differentials than the group without pneumonia, as shown in children group. CONCLUSION: Our results suggest that the immunologic reaction to viral insults may be associated with age, sex and underlying diseases, and that unknown herd immunity may affect populations. The patients with underlying diseases, especially in older patients may have immunologic insufficiency that is associated with immunologic consumption by the underlying diseases.",2012 Mar 26,"['Rhim, Jung-Woo', 'Go, Eun-Ji', 'Lee, Kyung-Yil', 'Youn, You-Sook', 'Kim, Myung-Sook', 'Park, Sun Hee', 'Kim, Ji-Chang', 'Kang, Jin-Han']",Int Arch Med,,,True
11ad2acc16067afbf2ce40d422647c3d899ecbd4,PMC,Cough aerosol in healthy participants: fundamental knowledge to optimize droplet-spread infectious respiratory disease management,http://dx.doi.org/10.1186/1471-2466-12-11,PMC3331822,22436202,CC BY,"BACKGROUND: The Influenza A H1N1 virus can be transmitted via direct, indirect, and airborne route to non-infected subjects when an infected patient coughs, which expels a number of different sized droplets to the surrounding environment as an aerosol. The objective of the current study was to characterize the human cough aerosol pattern with the aim of developing a standard human cough bioaerosol model for Influenza Pandemic control. METHOD: 45 healthy non-smokers participated in the open bench study by giving their best effort cough. A laser diffraction system was used to obtain accurate, time-dependent, quantitative measurements of the size and number of droplets expelled by the cough aerosol. RESULTS: Voluntary coughs generated droplets ranging from 0.1 - 900 microns in size. Droplets of less than one-micron size represent 97% of the total number of measured droplets contained in the cough aerosol. Age, sex, weight, height and corporal mass have no statistically significant effect on the aerosol composition in terms of size and number of droplets. CONCLUSIONS: We have developed a standard human cough aerosol model. We have quantitatively characterized the pattern, size, and number of droplets present in the most important mode of person-to-person transmission of IRD: the cough bioaerosol. Small size droplets (< 1 μm) predominated the total number of droplets expelled when coughing. The cough aerosol is the single source of direct, indirect and/or airborne transmission of respiratory infections like the Influenza A H1N1 virus. STUDY DESIGN: Open bench, Observational, Cough, Aerosol study",2012 Mar 21,"['Zayas, Gustavo', 'Chiang, Ming C', 'Wong, Eric', 'MacDonald, Fred', 'Lange, Carlos F', 'Senthilselvan, Ambikaipakan', 'King, Malcolm']",BMC Pulm Med,,,True
4e388424e65f63b5cc6b567b0980d430cb2d738c,PMC,Transmission Electron Microscopy Studies of Cellular Responses to Entry of Virions: One Kind of Natural Nanobiomaterial,http://dx.doi.org/10.1155/2012/596589,PMC3332201,22567012,CC BY,"Virions are one kind of nanoscale pathogen and are able to infect living cells of animals, plants, and bacteria. The infection is an intrinsic property of the virions, and the biological process provides a good model for studying how these nanoparticles enter into cells. During the infection, the viruses employ different strategies to which the cells have developed respective responses. For this paper, we chose Bombyx mori cypovirus 1 (BmCPV-1) interactions with midgut cells from silkworm, and severe acute respiratory syndrome (SARS) associated coronavirus interactions with Vero E6 cells, as examples to demonstrate the response of eukaryotic cells to two different types of virus from our previous studies. The bacteriophage-bacteria interactions are also introduced to elucidate how the bacteriophage conquers the barrier of cell walls in the prokaryotic cells to transport genome into the host.",2012 Apr 11,"['Liu, Zheng', 'Liu, Shuyu', 'Cui, Jinming', 'Tan, Yurong', 'He, Jian', 'Zhang, Jingqiang']",Int J Cell Biol,,,True
695f0e7afa181c640a015a3b43d1ae401435107a,PMC,"Coordination and resource-related difficulties encountered by Quebec's public health specialists and infectious diseases/medical microbiologists in the management of A (H1N1) - a mixed-method, exploratory survey",http://dx.doi.org/10.1186/1471-2458-12-115,PMC3332281,22325707,CC BY,"BACKGROUND: In Quebec, the influenza A (H1N1) pandemic was managed using a top-down style that left many involved players with critical views and frustrations. We aimed to describe physicians' perceptions - infectious diseases specialists/medical microbiologists (IDMM) and public health/preventive medicine specialists (PHPMS) - in regards to issues encountered with the pandemics management at the physician level and highlight suggested improvements for future healthcare emergencies. METHODS: In April 2010, Quebec IDMM and PHPMS physicians were invited to anonymously complete a web-based learning needs assessment. The survey included both open-ended and multiple-choice questions. Descriptive statistics were used to report on the frequency distribution of multiple choice responses whereas thematic content analysis was used to analyse qualitative data generated from the survey and help understand respondents' experience and perceptions with the pandemics. RESULTS: Of the 102 respondents, 85.3% reported difficulties or frustrations in their practice during the pandemic. The thematic analysis revealed two core themes describing the problems experienced in the pandemic management: coordination and resource-related difficulties. Coordination issues included communication, clinical practice guidelines, decision-making, roles and responsibilities, epidemiological investigation, and public health expert advisory committees. Resources issues included laboratory resources, patient management, and vaccination process. CONCLUSION: Together, the quantitative and qualitative data suggest a need for improved coordination, a better definition of roles and responsibilities, increased use of information technologies, merged communications, and transparency in the decisional process. Increased flexibility and less contradiction in clinical practice guidelines from different sources and increased laboratory/clinical capacity were felt critical to the proper management of infectious disease emergencies.",2012 Feb 10,"['Nhan, Charles', 'Laprise, Réjean', 'Douville-Fradet, Monique', 'Macdonald, Mary Ellen', 'Quach, Caroline']",BMC Public Health,,,True
d17d9c2e082583da2dba7cfc61995f5af37e6851,PMC,Protective Immunity to Listeria Monocytogenes Infection Mediated by Recombinant Listeria innocua Harboring the VGC Locus,http://dx.doi.org/10.1371/journal.pone.0035503,PMC3334901,22536395,CC BY,"In this study we propose a novel bacterial vaccine strategy where non-pathogenic bacteria are complemented with traits desirable for the induction of protective immunity. To illustrate the proof of principle of this novel vaccination strategy, we use the model organism of intracellular immunity Listeria. We introduced a, low copy number BAC-plasmid harbouring the virulence gene cluster (vgc) of L. monocytogenes (Lm) into the non-pathogenic L. innocua (L.inn) strain and examined for its ability to induce protective cellular immunity. The resulting strain (L.inn::vgc) was attenuated for virulence in vivo and showed a strongly reduced host detrimental inflammatory response compared to Lm. Like Lm, L.inn::vgc induced the production of Type I Interferon's and protection was mediated by Listeria-specific CD8(+) T cells. Rational vaccine design whereby avirulent strains are equipped with the capabilities to induce protection but lack detrimental inflammatory effects offer great promise towards future studies using non-pathogenic bacteria as vectors for vaccination.",2012 Apr 19,"['Mohamed, Walid', 'Sethi, Shneh', 'Tchatalbachev, Svetlin', 'Darji, Ayub', 'Chakraborty, Trinad']",PLoS One,,,True
ca7514c743f1cab0c939328f75ff231ba9d9079d,PMC,Anti-HIV-1 Activity of a New Scorpion Venom Peptide Derivative Kn2-7,http://dx.doi.org/10.1371/journal.pone.0034947,PMC3334916,22536342,CC BY,"For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1). In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC(50) value of 2.76 µg/ml (1.65 µM) and showed low cytotoxicity to host cells with a selective index (SI) of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1.",2012 Apr 19,"['Chen, Yaoqing', 'Cao, Luyang', 'Zhong, Maohua', 'Zhang, Yan', 'Han, Chen', 'Li, Qiaoli', 'Yang, Jingyi', 'Zhou, Dihan', 'Shi, Wei', 'He, Benxia', 'Liu, Fang', 'Yu, Jie', 'Sun, Ying', 'Cao, Yuan', 'Li, Yaoming', 'Li, Wenxin', 'Guo, Deying', 'Cao, Zhijian', 'Yan, Huimin']",PLoS One,,,True
21268687c8044a9acd561589e1f291f0843c6678,PMC,Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing,http://dx.doi.org/10.1371/journal.pone.0035009,PMC3334963,22536348,CC BY,"BACKGROUND: The Manila clam (Ruditapes philippinarum) is a worldwide cultured bivalve species with important commercial value. Diseases affecting this species can result in large economic losses. Because knowledge of the molecular mechanisms of the immune response in bivalves, especially clams, is scarce and fragmentary, we sequenced RNA from immune-stimulated R. philippinarum hemocytes by 454-pyrosequencing to identify genes involved in their immune defense against infectious diseases. METHODOLOGY AND PRINCIPAL FINDINGS: High-throughput deep sequencing of R. philippinarum using 454 pyrosequencing technology yielded 974,976 high-quality reads with an average read length of 250 bp. The reads were assembled into 51,265 contigs and the 44.7% of the translated nucleotide sequences into protein were annotated successfully. The 35 most frequently found contigs included a large number of immune-related genes, and a more detailed analysis showed the presence of putative members of several immune pathways and processes like the apoptosis, the toll like signaling pathway and the complement cascade. We have found sequences from molecules never described in bivalves before, especially in the complement pathway where almost all the components are present. CONCLUSIONS: This study represents the first transcriptome analysis using 454-pyrosequencing conducted on R. philippinarum focused on its immune system. Our results will provide a rich source of data to discover and identify new genes, which will serve as a basis for microarray construction and the study of gene expression as well as for the identification of genetic markers. The discovery of new immune sequences was very productive and resulted in a large variety of contigs that may play a role in the defense mechanisms of Ruditapes philippinarum.",2012 Apr 19,"['Moreira, Rebeca', 'Balseiro, Pablo', 'Planas, Josep V.', 'Fuste, Berta', 'Beltran, Sergi', 'Novoa, Beatriz', 'Figueras, Antonio']",PLoS One,,,True
69ed0332751ba504d01cf6d6c266c9ae499ceb38,PMC,Airflow Dynamics of Coughing in Healthy Human Volunteers by Shadowgraph Imaging: An Aid to Aerosol Infection Control,http://dx.doi.org/10.1371/journal.pone.0034818,PMC3335026,22536332,CC BY,"Cough airflow dynamics have been previously studied using a variety of experimental methods. In this study, real-time, non-invasive shadowgraph imaging was applied to obtain additional analyses of cough airflows produced by healthy volunteers. Twenty healthy volunteers (10 women, mean age 32.2±12.9 years; 10 men, mean age 25.3±2.5 years) were asked to cough freely, then into their sleeves (as per current US CDC recommendations) in this study to analyze cough airflow dynamics. For the 10 females (cases 1–10), their maximum detectable cough propagation distances ranged from 0.16–0.55 m, with maximum derived velocities of 2.2–5.0 m/s, and their maximum detectable 2-D projected areas ranged from 0.010–0.11 m(2), with maximum derived expansion rates of 0.15–0.55 m(2)/s. For the 10 males (cases 11–20), their maximum detectable cough propagation distances ranged from 0.31–0.64 m, with maximum derived velocities of 3.2–14 m/s, and their maximum detectable 2-D projected areas ranged from 0.04–0.14 m(2), with maximum derived expansion rates of 0.25–1.4 m(2)/s. These peak velocities were measured when the visibility of the exhaled airflows was optimal and compare favorably with those reported previously using other methods, and may be seen as a validation of these previous approaches in a more natural setting. However, the propagation distances can only represent a lower limit due to the inability of the shadowgraph method to visualize these cough airflows once their temperature cools to that of the ambient air, which is an important limitation of this methodology. The qualitative high-speed video footage of these volunteers coughing into their sleeves demonstrates that although this method rarely completely blocks the cough airflow, it decelerates, splits and redirects the airflow, eventually reducing its propagation. The effectiveness of this intervention depends on optimum positioning of the arm over the nose and mouth during coughing, though unsightly stains on sleeves may make it unacceptable to some.",2012 Apr 20,"['Tang, Julian W.', 'Nicolle, Andre', 'Pantelic, Jovan', 'Koh, Gerald C.', 'Wang, Liang De', 'Amin, Muhammad', 'Klettner, Christian A.', 'Cheong, David K. W.', 'Sekhar, Chandra', 'Tham, Kwok Wai']",PLoS One,,,True
962c58e6dc9c1ea550eb51ce70b0d7c83dc7eff6,PMC,Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus,http://dx.doi.org/10.1371/journal.pone.0035421,PMC3335060,22536382,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS) emerged in China in 2002 and spread to other countries before brought under control. Because of a concern for reemergence or a deliberate release of the SARS coronavirus, vaccine development was initiated. Evaluations of an inactivated whole virus vaccine in ferrets and nonhuman primates and a virus-like-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologic-type lung disease. DESIGN: Four candidate vaccines for humans with or without alum adjuvant were evaluated in a mouse model of SARS, a VLP vaccine, the vaccine given to ferrets and NHP, another whole virus vaccine and an rDNA-produced S protein. Balb/c or C57BL/6 mice were vaccinated IM on day 0 and 28 and sacrificed for serum antibody measurements or challenged with live virus on day 56. On day 58, challenged mice were sacrificed and lungs obtained for virus and histopathology. RESULTS: All vaccines induced serum neutralizing antibody with increasing dosages and/or alum significantly increasing responses. Significant reductions of SARS-CoV two days after challenge was seen for all vaccines and prior live SARS-CoV. All mice exhibited histopathologic changes in lungs two days after challenge including all animals vaccinated (Balb/C and C57BL/6) or given live virus, influenza vaccine, or PBS suggesting infection occurred in all. Histopathology seen in animals given one of the SARS-CoV vaccines was uniformly a Th2-type immunopathology with prominent eosinophil infiltration, confirmed with special eosinophil stains. The pathologic changes seen in all control groups lacked the eosinophil prominence. CONCLUSIONS: These SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV. However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced. Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated.",2012 Apr 20,"['Tseng, Chien-Te', 'Sbrana, Elena', 'Iwata-Yoshikawa, Naoko', 'Newman, Patrick C.', 'Garron, Tania', 'Atmar, Robert L.', 'Peters, Clarence J.', 'Couch, Robert B.']",PLoS One,,,True
9b034efc9d262e8687f1ad7adb78fa7374d3e5ad,PMC,The Influence of Meteorology on the Spread of Influenza: Survival Analysis of an Equine Influenza (A/H3N8) Outbreak,http://dx.doi.org/10.1371/journal.pone.0035284,PMC3335077,22536366,CC BY,"The influences of relative humidity and ambient temperature on the transmission of influenza A viruses have recently been established under controlled laboratory conditions. The interplay of meteorological factors during an actual influenza epidemic is less clear, and research into the contribution of wind to epidemic spread is scarce. By applying geostatistics and survival analysis to data from a large outbreak of equine influenza (A/H3N8), we quantified the association between hazard of infection and air temperature, relative humidity, rainfall, and wind velocity, whilst controlling for premises-level covariates. The pattern of disease spread in space and time was described using extraction mapping and instantaneous hazard curves. Meteorological conditions at each premises location were estimated by kriging daily meteorological data and analysed as time-lagged time-varying predictors using generalised Cox regression. Meteorological covariates time-lagged by three days were strongly associated with hazard of influenza infection, corresponding closely with the incubation period of equine influenza. Hazard of equine influenza infection was higher when relative humidity was <60% and lowest on days when daily maximum air temperature was 20–25°C. Wind speeds >30 km hour(−1) from the direction of nearby infected premises were associated with increased hazard of infection. Through combining detailed influenza outbreak and meteorological data, we provide empirical evidence for the underlying environmental mechanisms that influenced the local spread of an outbreak of influenza A. Our analysis supports, and extends, the findings of studies into influenza A transmission conducted under laboratory conditions. The relationships described are of direct importance for managing disease risk during influenza outbreaks in horses, and more generally, advance our understanding of the transmission of influenza A viruses under field conditions.",2012 Apr 20,"['Firestone, Simon M.', 'Cogger, Naomi', 'Ward, Michael P.', 'Toribio, Jenny-Ann L. M. L.', 'Moloney, Barbara J.', 'Dhand, Navneet K.']",PLoS One,,,True
0cf8f9fb2f0481a0e6a4b83cbffb07acfa20d6b0,PMC,Synthetic Biology: Mapping the Scientific Landscape,http://dx.doi.org/10.1371/journal.pone.0034368,PMC3335118,22539946,CC BY,"This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA) of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves.",2012 Apr 23,"['Oldham, Paul', 'Hall, Stephen', 'Burton, Geoff']",PLoS One,,,True
b2b5a490834c8b80177d322022e6c5c0828a5eaa,PMC,Schizophrenia: A Pathogenetic Autoimmune Disease Caused by Viruses and Pathogens and Dependent on Genes,http://dx.doi.org/10.4061/2011/128318,PMC3335463,22567321,CC BY,"Many genes have been implicated in schizophrenia as have viral prenatal or adult infections and toxoplasmosis or Lyme disease. Several autoantigens also target key pathology-related proteins. These factors are interrelated. Susceptibility genes encode for proteins homologous to those of the pathogens while the autoantigens are homologous to pathogens' proteins, suggesting that the risk-promoting effects of genes and risk factors are conditional upon each other, and dependent upon protein matching between pathogen and susceptibility gene products. Pathogens' proteins may act as dummy ligands, decoy receptors, or via interactome interference. Many such proteins are immunogenic suggesting that antibody mediated knockdown of multiple schizophrenia gene products could contribute to the disease, explaining the immune activation in the brain and lymphocytes in schizophrenia, and the preponderance of immune-related gene variants in the schizophrenia genome. Schizophrenia may thus be a “pathogenetic” autoimmune disorder, caused by pathogens, genes, and the immune system acting together, and perhaps preventable by pathogen elimination, or curable by the removal of culpable antibodies and antigens.",2011 May 26,"Carter, C. J.",J Pathog,,,True
05bdc3cf6dad125ad6539580352cb341eeaec2b1,PMC,Activation of P2X(7) Receptor by ATP Plays an Important Role in Regulating Inflammatory Responses during Acute Viral Infection,http://dx.doi.org/10.1371/journal.pone.0035812,PMC3338466,22558229,CC BY,"Acute viral infection causes damages to the host due to uncontrolled viral replication but even replication deficient viral vectors can induce systemic inflammatory responses. Indeed, overactive host innate immune responses to viral vectors have led to devastating consequences. Macrophages are important innate immune cells that recognize viruses and induce inflammatory responses at the early stage of infection. However, tissue resident macrophages are not easily activated by the mere presence of virus suggesting that their activation requires additional signals from other cells in the tissue in order to trigger inflammatory responses. Previously, we have shown that the cross-talk between epithelial cells and macrophages generates synergistic inflammatory responses during adenoviral vector infection. Here, we investigated whether ATP is involved in the activation of macrophages to induce inflammatory responses during an acute adenoviral infection. Using a macrophage-epithelial cell co-culture system we demonstrated that ATP signaling through P2X(7) receptor (P2X(7)R) is required for induction of inflammatory mediators. We also showed that ATP-P2X(7)R signaling regulates inflammasome activation as inhibition or deficiency of P2X(7)R as well as caspase-1 significantly reduced IL-1β secretion. Furthermore, we found that intranasal administration of replication deficient adenoviral vectors in mice caused a high mortality in wild-type mice with symptoms of acute respiratory distress syndrome but the mice deficient in P2X(7)R or caspase-1 showed increased survival. In addition, wild-type mice treated with apyrase or inhibitors of P2X(7)R or caspase-1 showed higher rates of survival. The improved survival in the P2X(7)R deficient mice correlated with diminished levels of IL-1β and IL-6 and reduced neutrophil infiltration in the early phase of infection. These results indicate that ATP, released during viral infection, is an important inflammatory regulator that activates the inflammasome pathway and regulates inflammatory responses.",2012 Apr 25,"['Lee, Benjamin H.', 'Hwang, David M.', 'Palaniyar, Nades', 'Grinstein, Sergio', 'Philpott, Dana J.', 'Hu, Jim']",PLoS One,,,True
04d9df812fd77e1231263d42ab45e570cd94d956,PMC,Aerosol Generating Procedures and Risk of Transmission of Acute Respiratory Infections to Healthcare Workers: A Systematic Review,http://dx.doi.org/10.1371/journal.pone.0035797,PMC3338532,22563403,CC BY,"Aerosol generating procedures (AGPs) may expose health care workers (HCWs) to pathogens causing acute respiratory infections (ARIs), but the risk of transmission of ARIs from AGPs is not fully known. We sought to determine the clinical evidence for the risk of transmission of ARIs to HCWs caring for patients undergoing AGPs compared with the risk of transmission to HCWs caring for patients not undergoing AGPs. We searched PubMed, EMBASE, MEDLINE, CINAHL, the Cochrane Library, University of York CRD databases, EuroScan, LILACS, Indian Medlars, Index Medicus for SE Asia, international health technology agencies and the Internet in all languages for articles from 01/01/1990 to 22/10/2010. Independent reviewers screened abstracts using pre-defined criteria, obtained full-text articles, selected relevant studies, and abstracted data. Disagreements were resolved by consensus. The outcome of interest was risk of ARI transmission. The quality of evidence was rated using the GRADE system. We identified 5 case-control and 5 retrospective cohort studies which evaluated transmission of SARS to HCWs. Procedures reported to present an increased risk of transmission included [n; pooled OR(95%CI)] tracheal intubation [n = 4 cohort; 6.6 (2.3, 18.9), and n = 4 case-control; 6.6 (4.1, 10.6)], non-invasive ventilation [n = 2 cohort; OR 3.1(1.4, 6.8)], tracheotomy [n = 1 case-control; 4.2 (1.5, 11.5)] and manual ventilation before intubation [n = 1 cohort; OR 2.8 (1.3, 6.4)]. Other intubation associated procedures, endotracheal aspiration, suction of body fluids, bronchoscopy, nebulizer treatment, administration of O2, high flow O2, manipulation of O2 mask or BiPAP mask, defibrillation, chest compressions, insertion of nasogastric tube, and collection of sputum were not significant. Our findings suggest that some procedures potentially capable of generating aerosols have been associated with increased risk of SARS transmission to HCWs or were a risk factor for transmission, with the most consistent association across multiple studies identified with tracheal intubation.",2012 Apr 26,"['Tran, Khai', 'Cimon, Karen', 'Severn, Melissa', 'Pessoa-Silva, Carmem L.', 'Conly, John']",PLoS One,,,True
a23e98e1cc196167116f87f71aae771739bdf0d0,PMC,Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus,http://dx.doi.org/10.1371/journal.pone.0036238,PMC3338671,22558400,CC BY,"BACKGROUND: The white backed planthopper (WBPH), Sogatella furcifera (Horváth), causes great damage to many crops by direct feeding or transmitting plant viruses. Southern rice black-streaked dwarf virus (SRBSDV), transmitted by WBPH, has become a great threat to rice production in East Asia. METHODOLOGY/PRINCIPAL FINDINGS: By de novo transcriptome assembling and massive parallel pyrosequencing, we constructed two transcriptomes of WBPH and profiled the alternation of gene expression in response to SRBSDV infection in transcriptional level. Over 25 million reads of high-quality DNA sequences and 81388 different unigenes were generated using Illumina technology from both viruliferous and non-viruliferous WBPH. WBPH has a very similar gene ontological distribution to other two closely related rice planthoppers, Nilaparvata lugens and Laodelphax striatellus. 7291 microsatellite loci were also predicted which could be useful for further evolutionary analysis. Furthermore, comparative analysis of the two transcriptomes generated from viruliferous and non-viruliferous WBPH provided a list of candidate transcripts that potentially were elicited as a response to viral infection. Pathway analyses of a subset of these transcripts indicated that SRBSDV infection may perturb primary metabolism and the ubiquitin-proteasome pathways. In addition, 5.5% (181 out of 3315) of the genes in cell cytoskeleton organization pathway showed obvious changes. Our data also demonstrated that SRBSDV infection activated the immunity regulatory systems of WBPH, such as RNA interference, autophagy and antimicrobial peptide production. CONCLUSIONS/SIGNIFICANCE: We employed massively parallel pyrosequencing to collect ESTs from viruliferous and non-viruliferous samples of WBPH. 81388 different unigenes have been obtained. We for the first time described the direct effects of a Reoviridae family plant virus on global gene expression profiles of its insect vector using high-throughput sequencing. Our study will provide a road map for future investigations of the fascinating interactions between Reoviridae viruses and their insect vectors, and provide new strategies for crop protection.",2012 Apr 27,"['Xu, Yi', 'Zhou, Wenwu', 'Zhou, Yijun', 'Wu, Jianxiang', 'Zhou, Xueping']",PLoS One,,,True
aff7baf924af877c824d6c9c1132caa094342636,PMC,"Replication, Neurotropism, and Pathogenicity of Avian Paramyxovirus Serotypes 1–9 in Chickens and Ducks",http://dx.doi.org/10.1371/journal.pone.0034927,PMC3340391,22558104,CC0,"Avian paramyxovirus (APMV) serotypes 1–9 have been isolated from many different avian species. APMV-1 (Newcastle disease virus) is the only well-characterized serotype, because of the high morbidity, mortality, and economic loss caused by highly virulent strains. Very little is known about the pathogenesis, replication, virulence, and tropism of the other APMV serotypes. Here, this was evaluated for prototypes strains of APMV serotypes 2–9 in cell culture and in chickens and ducks. In cell culture, only APMV-1, -3 and -5 induced syncytium formation. In chicken DF1 cells, APMV-3 replicated with an efficiency approaching that of APMV-1, while APMV-2 and -5 replicated to lower, intermediate titers and the others were much lower. Mean death time (MDT) assay in chicken eggs and intracerebral pathogenicity index (ICPI) test in 1-day-old SPF chicks demonstrated that APMV types 2–9 were avirulent. Evaluation of replication in primary neuronal cells in vitro as well as in the brains of 1-day-old chicks showed that, among types 2–9, only APMV-3 was neurotropic, although this virus was not neurovirulent. Following intranasal infection of 1-day-old and 2-week-old chickens, replication of APMV types 2–9 was mostly restricted to the respiratory tract, although APMV-3 was neuroinvasive and neurotropic (but not neurovirulent) and also was found in the spleen. Experimental intranasal infection of 3-week-old mallard ducks with the APMVs did not produce any clinical signs (even for APMV-1) and exhibited restricted viral replication of the APMVs (including APMV-1) to the upper respiratory tract regardless of their isolation source, indicating avirulence of APMV types 1–9 in mallard ducks. The link between the presence of a furin cleavage site in the F protein, syncytium formation, systemic spread, and virulence that has been well-established with APMV-1 pathotypes was not evident with the other APMV serotypes.",2012 Apr 30,"['Kim, Shin-Hee', 'Xiao, Sa', 'Shive, Heather', 'Collins, Peter L.', 'Samal, Siba K.']",PLoS One,,,True
ba3522d00ecebd159c5b5dc90119df8642993c49,PMC,Influenza and SARS-Coronavirus Activating Proteases TMPRSS2 and HAT Are Expressed at Multiple Sites in Human Respiratory and Gastrointestinal Tracts,http://dx.doi.org/10.1371/journal.pone.0035876,PMC3340400,22558251,CC BY,"The type II transmembrane serine proteases TMPRSS2 and HAT activate influenza viruses and the SARS-coronavirus (TMPRSS2) in cell culture and may play an important role in viral spread and pathogenesis in the infected host. However, it is at present largely unclear to what extent these proteases are expressed in viral target cells in human tissues. Here, we show that both HAT and TMPRSS2 are coexpressed with 2,6-linked sialic acids, the major receptor determinant of human influenza viruses, throughout the human respiratory tract. Similarly, coexpression of ACE2, the SARS-coronavirus receptor, and TMPRSS2 was frequently found in the upper and lower aerodigestive tract, with the exception of the vocal folds, epiglottis and trachea. Finally, activation of influenza virus was conserved between human, avian and porcine TMPRSS2, suggesting that this protease might activate influenza virus in reservoir-, intermediate- and human hosts. In sum, our results show that TMPRSS2 and HAT are expressed by important influenza and SARS-coronavirus target cells and could thus support viral spread in the human host.",2012 Apr 30,"['Bertram, Stephanie', 'Heurich, Adeline', 'Lavender, Hayley', 'Gierer, Stefanie', 'Danisch, Simon', 'Perin, Paula', 'Lucas, Jared M.', 'Nelson, Peter S.', 'Pöhlmann, Stefan', 'Soilleux, Elizabeth J.']",PLoS One,,,True
d2263b3300cd722dfbadc7c40008126d95ab4af6,PMC,Patterns and influencing factor of synonymous codon usage in porcine circovirus,http://dx.doi.org/10.1186/1743-422X-9-68,PMC3341187,22416942,CC BY,"BACKGROUND: Analysis of codon usage can reveal much about the molecular evolution of the viruses. Nevertheless, little information about synonymous codon usage pattern of porcine circovirus (PCV) genome in the process of its evolution is available. In this study, to give a new understanding on the evolutionary characteristics of PCV and the effects of natural selection from its host on the codon usage pattern of the virus, Patterns and the key determinants of codon usage in PCV were examined. METHODS: We carried out comprehensive analysis on codon usage pattern in the PCV genome, by calculating relative synonymous codon usage (RSCU), effective number of codons (ENC), dinucleotides and nucleic acid content of the PCV genome. RESULTS: PCV genomes have relatively much lower content of GC and codon preference, this result shows that nucleotide constraints have a major impact on its synonymous codon usage. The results of the correspondence analysis indicate codon usage patterns of PCV of various genotypes, various subgenotypes changed greatly, and significant differences in codon usage patterns of Each virus of Circoviridae.There is much comparability between PCV and its host in their synonymous codon usage, suggesting that the natural selection pressure from the host factor also affect the codon usage patterns of PCV. In particular, PCV genotype II is in synonymous codon usage more similar to pig than to PCV genotype I, which may be one of the most important molecular mechanisms of PCV genotype II to cause disease. The calculations results of the relative abundance of dinucleotides indicate that the composition of dinucleotides also plays a key role in the variation found in synonymous codon usage in PCV. Furthermore, geographic factors, the general average hydrophobicity and the aromaticity may be related to the formation of codon usage patterns of PCV. CONCLUSION: The results of these studies suggest that synonymous codon usage pattern of PCV genome are the result of interaction between mutation pressure and natural selection from its host. The information from this study may not only have theoretical value in understanding the characteristics of synonymous codon usage in PCV genomes, but also have significant value for the molecular evolution of PCV.",2012 Mar 15,"['LIU, Xin-sheng', 'Zhang, Yong-guang', 'Fang, Yu-zhen', 'Wang, Yong-lu']",Virol J,,,True
6848f444e963e825730c6fbcf63b78b65d0efd3d,PMC,Development of a Humanized Antibody with High Therapeutic Potential against Dengue Virus Type 2,http://dx.doi.org/10.1371/journal.pntd.0001636,PMC3341331,22563515,CC BY,"BACKGROUND: Dengue virus (DENV) is a significant public health threat in tropical and subtropical regions of the world. A therapeutic antibody against the viral envelope (E) protein represents a promising immunotherapy for disease control. METHODOLOGY/PRINCIPAL FINDINGS: We generated seventeen novel mouse monoclonal antibodies (mAbs) with high reactivity against E protein of dengue virus type 2 (DENV-2). The mAbs were further dissected using recombinant E protein domain I-II (E-DI-II) and III (E-DIII) of DENV-2. Using plaque reduction neutralization test (PRNT) and mouse protection assay with lethal doses of DENV-2, we identified four serotype-specific mAbs that had high neutralizing activity against DENV-2 infection. Of the four, E-DIII targeting mAb DB32-6 was the strongest neutralizing mAb against diverse DENV-2 strains. Using phage display and virus-like particles (VLPs) we found that residue K310 in the E-DIII A-strand was key to mAb DB32-6 binding E-DIII. We successfully converted DB32-6 to a humanized version that retained potency for the neutralization of DENV-2 and did not enhance the viral infection. The DB32-6 showed therapeutic efficacy against mortality induced by different strains of DENV-2 in two mouse models even in post-exposure trials. CONCLUSIONS/SIGNIFICANCE: We used novel epitope mapping strategies, by combining phage display with VLPs, to identify the important A-strand epitopes with strong neutralizing activity. This study introduced potential therapeutic antibodies that might be capable of providing broad protection against diverse DENV-2 infections without enhancing activity in humans.",2012 May 1,"['Li, Pi-Chun', 'Liao, Mei-Ying', 'Cheng, Ping-Chang', 'Liang, Jian-Jong', 'Liu, I-Ju', 'Chiu, Chien-Yu', 'Lin, Yi-Ling', 'Chang, Gwong-Jen J.', 'Wu, Han-Chung']",PLoS Negl Trop Dis,,,True
1c0ae4beee003ecb59ff15f81ed8f22cd9451353,PMC,"Knowledge, attitudes and practices related to avian influenza among poultry workers in Nepal: a cross sectional study",http://dx.doi.org/10.1186/1471-2334-12-76,PMC3342178,22458535,CC BY,"BACKGROUND: Avian influenza is a considerable threat to global public health. Prevention and control depend on awareness and protective behaviours of the general population as well as high risk-groups. This study aims to explore the knowledge, attitudes and practices related to avian influenza among poultry workers in Nepal. METHODS: The study was based on a cross-sectional study design, using a structured questionnaire administered in face-to-face interviews with 96 poultry workers age 15 and above from the Rupandehi district in Nepal. RESULTS: The majority of respondents were male (80%), mean age was 35 (SD = 11.6). Nearly everybody was aware that AI cases had been detected in Nepal and that poultry workers were at risk for infection. The major sources of AI information were radio, TV and newspapers. Knowledge about preventive measures was high with regard to some behaviours (hand washing), but medium to low with regard to others (using cleaning and disinfecting procedures or protective clothing). Poultry workers who got their information from TV and newspapers and those who were more afraid of contracting AI had higher knowledge than those who did not. Being employed as compared to being an owner of a poultry farm as well as having a high level of knowledge was associated with practising more preventive behaviours. While on one hand many specific government control measures found a high degree of acceptance, a majority of study participants also thought that government control and compensation measures as a whole were insufficient. CONCLUSIONS: The study provides information about knowledge and practices regarding avian influenza among poultry workers in Nepal. It highlights the importance of targeting lack of knowledge as well as structural-material barriers to successfully build preparedness for a major outbreak situation.",2012 Mar 30,"['Neupane, Dinesh', 'Khanal, Vishnu', 'Ghimire, Kamal', 'Aro, Arja R', 'Leppin, Anja']",BMC Infect Dis,,,True
9399460a7a75b8ae8a4f5610fd1ecf05d21d2f17,PMC,Proteomics analysis of differentially expressed proteins in chicken trachea and kidney after infection with the highly virulent and attenuated coronavirus infectious bronchitis virus in vivo,http://dx.doi.org/10.1186/1477-5956-10-24,PMC3342233,22463732,CC BY,"BACKGROUND: Infectious bronchitis virus (IBV) is first to be discovered coronavirus which is probably endemic in all regions with intensive impact on poultry production. In this study, we used two-dimensional gel electrophoresis (2-DE) and two-dimensional fluorescence difference gel electrophoresis (2-DIGE), coupled with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS), to explore the global proteome profiles of trachea and kidney tissues from chicken at different stages infected in vivo with the highly virulent ck/CH/LDL/97I P(5 )strain of infectious bronchitis virus (IBV) and the embryo-passaged, attenuated ck/CH/LDL/97I P(115 )strain. RESULTS: Fifty-eight differentially expressed proteins were identified. Results demonstrated that some proteins which had functions in cytoskeleton organization, anti-oxidative stress, and stress response, showed different change patterns in abundance from chicken infected with the highly virulent ck/CH/LDL/97I P(5 )strain and those given the embryo-passaged, attenuated P(115 )stain. In addition, the dynamic transcriptional alterations of 12 selected proteins were analyzed by the real-time RT-PCR, and western blot analysis confirmed the change in abundance of heat shock proteins (HSP) beta-1, annexin A2, and annexin A5. CONCLUSIONS: The proteomic alterations described here may suggest that these changes to protein expression correlate with IBV virus' virulence in chicken, hence provides valuable insights into the interactions of IBV with its host and may also assist with investigations of the pathogenesis of IBV and other coronavirus infections.",2012 Mar 31,"['Cao, Zhongzan', 'Han, Zongxi', 'Shao, Yuhao', 'Liu, Xiaoli', 'Sun, Junfeng', 'Yu, Demin', 'Kong, Xiangang', 'Liu, Shengwang']",Proteome Sci,,,True
b3deae058a2e470aac4ba8f9425c6150575f1522,PMC,Viral Findings in Adult Hematological Patients with Neutropenia,http://dx.doi.org/10.1371/journal.pone.0036543,PMC3343003,22570724,CC BY,"BACKGROUND: Until recently, viral infections in patients with hematological malignancies were concerns primarily in allogeneic hematopoietic stem cell transplant (HSCT) recipients. During the last years, changed treatment regimens for non-transplanted patients with hematological malignancies have had potential to increase the incidence of viral infections in this group. In this study, we have prospectively investigated the prevalence of a broad range of respiratory viruses in nasopharyngeal aspirate (NPA) as well as viruses that commonly reactivate after allogeneic HSCT. METHODOLOGY/PRINCIPAL FINDINGS: Patients with hematological malignancies and therapy induced neutropenia (n = 159) were screened regarding a broad range of common respiratory viruses in the nasopharynx and for viruses commonly detected in severely immunosuppressed patients in peripheral blood. Quantitative PCR was used for detection of viruses. A viral pathogen was detected in 35% of the patients. The detection rate was rather similar in blood (22%) and NPA (18%) with polyoma BK virus and rhinovirus as dominating pathogens in blood and NPA, respectively. Patients with chronic lymphocytic leukemia (CLL) (p<0.01) and patients with fever (p<0.001) were overrepresented in the virus-positive group. Furthermore, viral findings in NPA were associated with upper respiratory symptoms (URTS) (p<0.0001). CONCLUSIONS/SIGNIFICANCE: Both respiratory viral infections and low titers of viruses in blood from patients with neutropenia were common. Patients with CLL and patients with fever were independently associated to these infections, and viral findings in NPA were associated to URTS indicating active infection. These findings motivate further studies on viruses' impact on this patient category and their potential role as causative agents of fever during neutropenia.",2012 May 3,"['Öhrmalm, Lars', 'Wong, Michelle', 'Aust, Carl', 'Ljungman, Per', 'Norbeck, Oscar', 'Broliden, Kristina', 'Tolfvenstam, Thomas']",PLoS One,,,True
3c988a00ed94308e36a8814b391ead01480efb60,PMC,A Single Polar Residue and Distinct Membrane Topologies Impact the Function of the Infectious Bronchitis Coronavirus E Protein,http://dx.doi.org/10.1371/journal.ppat.1002674,PMC3343006,22570613,CC BY,"The coronavirus E protein is a small membrane protein with a single predicted hydrophobic domain (HD), and has a poorly defined role in infection. The E protein is thought to promote virion assembly, which occurs in the Golgi region of infected cells. It has also been implicated in the release of infectious particles after budding. The E protein has ion channel activity in vitro, although a role for channel activity in infection has not been established. Furthermore, the membrane topology of the E protein is of considerable debate, and the protein may adopt more than one topology during infection. We previously showed that the HD of the infectious bronchitis virus (IBV) E protein is required for the efficient release of infectious virus, an activity that correlated with disruption of the secretory pathway. Here we report that a single residue within the hydrophobic domain, Thr16, is required for secretory pathway disruption. Substitutions of other residues for Thr16 were not tolerated. Mutations of Thr16 did not impact virus assembly as judged by virus-like particle production, suggesting that alteration of secretory pathway and assembly are independent activities. We also examined how the membrane topology of IBV E affected its function by generating mutant versions that adopted either a transmembrane or membrane hairpin topology. We found that a transmembrane topology was required for disrupting the secretory pathway, but was less efficient for virus-like particle production. The hairpin version of E was unable to disrupt the secretory pathway or produce particles. The findings reported here identify properties of the E protein that are important for its function, and provide insight into how the E protein may perform multiple roles during infection.",2012 May 3,"['Ruch, Travis R.', 'Machamer, Carolyn E.']",PLoS Pathog,,,True
31444b90fc581b9b42bfbbb70e4ad4dcf1aca613,PMC,"1,3-Diphenyl-4,5-dihydro-1H-pyrazol-5-one",http://dx.doi.org/10.1107/S1600536812009567,PMC3343981,22589890,CC BY,"In the title pyrazolone derivative, C(15)H(12)N(2)O, the five-membered ring is approximately planar (r.m.s. deviation = 0.018 Å), and the N- and C-bound benzene rings are inclined to this plane [dihedral angles = 21.45 (10) and 6.96 (10)°, respectively] and form a dihedral angle of 20.42 (10)° with each other. Supramolecular layers are formed in the crystal structure via C—H⋯O and C—H⋯N interactions, and these are assembled into double layers by C—H⋯π and π–π interactions between the pyrazole and C-bound benzene rings [ring centroid–centroid distance = 3.6476 (12) Å]. The double layers stack along the a axis being connected by π–π interactions between the N- and C-bound benzene rings [ring centroid–centroid distance = 3.7718 (12) Å].",2012 Mar 10,"['Baddeley, Thomas C.', 'Wardell, Solange M. S. V.', 'Tiekink, Edward R. T.', 'Wardell, James L.']",Acta Crystallogr Sect E Struct Rep Online,,,True
f6a9c8aafc0ead13250df25ee0f5882f9aeedd76,PMC,Phages and HIV-1: From Display to Interplay,http://dx.doi.org/10.3390/ijms13044727,PMC3344243,22606007,CC BY,"The complex hide-and-seek game between HIV-1 and the host immune system has impaired the development of an efficient vaccine. In addition, the high variability of the virus impedes the long-term control of viral replication by small antiviral drugs. For more than 20 years, phage display technology has been intensively used in the field of HIV-1 to explore the epitope landscape recognized by monoclonal and polyclonal HIV-1-specific antibodies, thereby providing precious data about immunodominant and neutralizing epitopes. In parallel, biopanning experiments with various combinatorial or antibody fragment libraries were conducted on viral targets as well as host receptors to identify HIV-1 inhibitors. Besides these applications, phage display technology has been applied to characterize the enzymatic specificity of the HIV-1 protease. Phage particles also represent valuable alternative carriers displaying various HIV-1 antigens to the immune system and eliciting antiviral responses. This review presents and summarizes the different studies conducted with regard to the nature of phage libraries, target display mode and biopanning procedures.",2012 Apr 13,"['Delhalle, Sylvie', 'Schmit, Jean-Claude', 'Chevigné, Andy']",Int J Mol Sci,,,True
d5a2557d0cb42ffcb93f693d7fa4e70fb817e20b,PMC,The CEA/CD3-Bispecific Antibody MEDI-565 (MT111) Binds a Nonlinear Epitope in the Full-Length but Not a Short Splice Variant of CEA,http://dx.doi.org/10.1371/journal.pone.0036412,PMC3344869,22574157,CC BY,"MEDI-565 (also known as MT111) is a bispecific T-cell engager (BiTE®) antibody in development for the treatment of patients with cancers expressing carcinoembryonic antigen (CEA). MEDI-565 binds CEA on cancer cells and CD3 on T cells to induce T-cell mediated killing of cancer cells. To understand the molecular basis of human CEA recognition by MEDI-565 and how polymorphisms and spliced forms of CEA may affect MEDI-565 activity, we mapped the epitope of MEDI-565 on CEA using mutagenesis and homology modeling approaches. We found that MEDI-565 recognized a conformational epitope in the A2 domain comprised of amino acids 326–349 and 388–410, with critical residues F(326), T(328), N(333), V(388), G(389), P(390), E(392), I(408), and N(410). Two non-synonymous single-nucleotide polymorphisms (SNPs) (rs10407503, rs7249230) were identified in the epitope region, but they are found at low homozygosity rates. Searching the National Center for Biotechnology Information GenBank® database, we further identified a single, previously uncharacterized mRNA splice variant of CEA that lacks a portion of the N-terminal domain, the A1 and B1 domains, and a large portion of the A2 domain. Real-time quantitative polymerase chain reaction analysis of multiple cancers showed widespread expression of full-length CEA in these tumors, with less frequent but concordant expression of the CEA splice variant. Because the epitope was largely absent from the CEA splice variant, MEDI-565 did not bind or mediate T-cell killing of cells solely expressing this form of CEA. In addition, the splice variant did not interfere with MEDI-565 binding or activity when co-expressed with full-length CEA. Thus MEDI-565 may broadly target CEA-positive tumors without regard for expression of the short splice variant of CEA. Together our data suggest that MEDI-565 activity will neither be impacted by SNPs nor by a splice variant of CEA.",2012 May 4,"['Peng, Li', 'Oberst, Michael D.', 'Huang, Jiaqi', 'Brohawn, Philip', 'Morehouse, Chris', 'Lekstrom, Kristen', 'Baeuerle, Patrick A.', 'Wu, Herren', 'Yao, Yihong', 'Coats, Steven R.', 'Dall’Acqua, William', 'Damschroder, Melissa', 'Hammond, Scott A.']",PLoS One,,,True
0867cf1922a634eefb3a3ad07f4dc6c9c94828ea,PMC,High Throughput Screening for Small Molecule Enhancers of the Interferon Signaling Pathway to Drive Next-Generation Antiviral Drug Discovery,http://dx.doi.org/10.1371/journal.pone.0036594,PMC3344904,22574190,CC BY,"Most of current strategies for antiviral therapeutics target the virus specifically and directly, but an alternative approach to drug discovery might be to enhance the immune response to a broad range of viruses. Based on clinical observation in humans and successful genetic strategies in experimental models, we reasoned that an improved interferon (IFN) signaling system might better protect against viral infection. Here we aimed to identify small molecular weight compounds that might mimic this beneficial effect and improve antiviral defense. Accordingly, we developed a cell-based high-throughput screening (HTS) assay to identify small molecules that enhance the IFN signaling pathway components. The assay is based on a phenotypic screen for increased IFN-stimulated response element (ISRE) activity in a fully automated and robust format (Z′>0.7). Application of this assay system to a library of 2240 compounds (including 2160 already approved or approvable drugs) led to the identification of 64 compounds with significant ISRE activity. From these, we chose the anthracycline antibiotic, idarubicin, for further validation and mechanism based on activity in the sub-µM range. We found that idarubicin action to increase ISRE activity was manifest by other members of this drug class and was independent of cytotoxic or topoisomerase inhibitory effects as well as endogenous IFN signaling or production. We also observed that this compound conferred a consequent increase in IFN-stimulated gene (ISG) expression and a significant antiviral effect using a similar dose-range in a cell-culture system inoculated with encephalomyocarditis virus (EMCV). The antiviral effect was also found at compound concentrations below the ones observed for cytotoxicity. Taken together, our results provide proof of concept for using activators of components of the IFN signaling pathway to improve IFN efficacy and antiviral immune defense as well as a validated HTS approach to identify small molecules that might achieve this therapeutic benefit.",2012 May 4,"['Patel, Dhara A.', 'Patel, Anand C.', 'Nolan, William C.', 'Zhang, Yong', 'Holtzman, Michael J.']",PLoS One,,,True
1731adb9524645ed8e10be851313f796f82459c0,PMC,The Coronavirus E Protein: Assembly and Beyond,http://dx.doi.org/10.3390/v4030363,PMC3347032,22590676,CC BY,"The coronavirus E protein is a small membrane protein that has an important role in the assembly of virions. Recent studies have indicated that the E protein has functions during infection beyond assembly, including in virus egress and in the host stress response. Additionally, the E protein has ion channel activity, interacts with host proteins, and may have multiple membrane topologies. The goal of this review is to highlight the properties and functions of the E protein, and speculate on how they may be related.",2012 Mar 8,"['Ruch, Travis R.', 'Machamer, Carolyn E.']",Viruses,,,True
3c9d07cac8fdfacf5199e81f35aa6dd4dc7e49ab,PMC,Feline Immunodeficiency Virus in South America,http://dx.doi.org/10.3390/v4030383,PMC3347033,22590677,CC BY,"The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV) have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species). Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV) causes an immune system disease in domestic cats (Felis catus) involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs) in South America.",2012 Mar 14,"['Teixeira, Bruno M.', 'Hagiwara, Mitika K.', 'Cruz, Juliano C. M.', 'Hosie, Margaret J.']",Viruses,,,True
c4db01f9d02579bbc25384c6f72a5ce25a4dba0d,PMC,Interplay between Interferon-Mediated Innate Immunity and Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.3390/v4040424,PMC3347317,22590680,CC BY,"Innate immunity is the first line of defense against viral infection, and in turn, viruses have evolved to evade host immune surveillance. As a result, viruses may persist in host and develop chronic infections. Type I interferons (IFN-α/β) are among the most potent antiviral cytokines triggered by viral infections. Porcine reproductive and respiratory syndrome (PRRS) is a disease of pigs that is characterized by negligible induction of type I IFNs and viral persistence for an extended period. For IFN production, RIG-I/MDA5 and JAK-STAT pathways are two major signaling pathways, and recent studies indicate that PRRS virus is armed to modulate type I IFN responses during infection. This review describes the viral strategies for modulation of type I IFN responses. At least three non–structural proteins (Nsp1, Nsp2, and Nsp11) and a structural protein (N nucleocapsid protein) have been identified and characterized to play roles in the IFN suppression and NF-κB pathways. Nsp’s are early proteins while N is a late protein, suggesting that additional signaling pathways may be involved in addition to the IFN pathway. The understanding of molecular bases for virus-mediated modulation of host innate immune signaling will help us design new generation vaccines and control PRRS.",2012 Apr 2,"['Sun, Yan', 'Han, Mingyuan', 'Kim, Chiyong', 'Calvert, Jay G.', 'Yoo, Dongwan']",Viruses,,,True
9751ae6c4cdecf8bfb8934f93a9b2aadf3d4737f,PMC,Daphne Genkwa Sieb. et Zucc. Water-Soluble Extracts Act on Enterovirus 71 by Inhibiting Viral Entry,http://dx.doi.org/10.3390/v4040539,PMC3347322,22590685,CC BY,"Dried flowers of Daphne genkwa Sieb. et Zucc. (Thymelaeaceae) are a Chinese herbal medicine used as an abortifacient with purgative, diuretic and anti-inflammatory activities. However, the activity of this medicine against enteroviral infections has not been investigated. The water-extract of dried buds of D. genkwa Sieb. et Zucc. (DGFW) was examined against various strains of enterovirus 71 (EV71) by neutralization assay, and its initial mode of action was characterized by time-of-addition assay followed by attachment and penetration assays. Pretreatment of DGFW with virus abolished viral replication, indicating that DGFW inhibits EV71 by targeting the virus. GFW exerts its anti-EV71 effects by inhibiting viral entry without producing cytotoxic side effects and thus provides a potential agent for antiviral chemotherapeutics.",2012 Apr 11,"['Chang, Chia-Wen', 'Leu, Yan-Lii', 'Horng, Jim-Tong']",Viruses,,,True
8ba02094773754fa07bf75af55fdddede4129f59,PMC,Daphne Genkwa Sieb. et Zucc. Water-Soluble Extracts Act on Enterovirus 71 by Inhibiting Viral Entry,http://dx.doi.org/10.3390/v4040539,PMC3347322,22590685,CC BY,"Dried flowers of Daphne genkwa Sieb. et Zucc. (Thymelaeaceae) are a Chinese herbal medicine used as an abortifacient with purgative, diuretic and anti-inflammatory activities. However, the activity of this medicine against enteroviral infections has not been investigated. The water-extract of dried buds of D. genkwa Sieb. et Zucc. (DGFW) was examined against various strains of enterovirus 71 (EV71) by neutralization assay, and its initial mode of action was characterized by time-of-addition assay followed by attachment and penetration assays. Pretreatment of DGFW with virus abolished viral replication, indicating that DGFW inhibits EV71 by targeting the virus. GFW exerts its anti-EV71 effects by inhibiting viral entry without producing cytotoxic side effects and thus provides a potential agent for antiviral chemotherapeutics.",2012 Apr 11,"['Chang, Chia-Wen', 'Leu, Yan-Lii', 'Horng, Jim-Tong']",Viruses,,,False
a1add6ab708156c28d4dfa6e0bd825a53c38e418,PMC,"Ready, Set, Fuse! The Coronavirus Spike Protein and Acquisition of Fusion Competence",http://dx.doi.org/10.3390/v4040557,PMC3347323,22590686,CC BY,"Coronavirus-cell entry programs involve virus-cell membrane fusions mediated by viral spike (S) proteins. Coronavirus S proteins acquire membrane fusion competence by receptor interactions, proteolysis, and acidification in endosomes. This review describes our current understanding of the S proteins, their interactions with and their responses to these entry triggers. We focus on receptors and proteases in prompting entry and highlight the type II transmembrane serine proteases (TTSPs) known to activate several virus fusion proteins. These and other proteases are essential cofactors permitting coronavirus infection, conceivably being in proximity to cell-surface receptors and thus poised to split entering spike proteins into the fragments that refold to mediate membrane fusion. The review concludes by noting how understanding of coronavirus entry informs antiviral therapies.",2012 Apr 12,"['Heald-Sargent, Taylor', 'Gallagher, Tom']",Viruses,,,True
71fd4bd89b7dc7a87a4cc7bdcb25be3e444becc4,PMC,Co-circulation of Four Human Coronaviruses (HCoVs) in Queensland Children with Acute Respiratory Tract Illnesses in 2004,http://dx.doi.org/10.3390/v4040637,PMC3347326,22590689,CC BY,"Acute respiratory illnesses (ARIs) with unconfirmed infectious aetiologies peak at different times of the year. Molecular diagnostic assays reduce the number of unconfirmed ARIs compared to serology- or culture-based techniques. Screening of 888 inpatient and outpatient respiratory specimens spanning late autumn through to early spring, 2004, identified the presence of a human coronavirus (HCoV) on 74 occasions (8.3% of all specimens and 26.3% of all respiratory virus detections). Prevalence peaked in August (late winter in the southern hemisphere) when they were detected in 21.9% of specimens tested. HCoV-HKU1 and HCoV-OC43 comprised 82.4% of all HCoVs detected. Positive specimens were used to develop novel reverse transcriptase real-time PCRs (RT-rtPCRs) for HCoV detection. An objective clinical severity score was assigned to each positive HCoV patient. Severity scores were similar to those from a random selection of young children who were positive for respiratory syncytial virus at a different time but from the same specimen population. During the cooler months of 2004, sensitive and specific RT-rtPCRs identified the concurrent circulation of all four HCoVs, a quarter of which co-occurred with another virus and most of which were from children under the age of two years.",2012 Apr 23,"['Mackay, Ian M.', 'Arden, Katherine E.', 'Speicher, David J.', 'O’Neil, Nicholas T.', 'McErlean, Peter K.', 'Greer, Ristan M.', 'Nissen, Michael D.', 'Sloots, Theo P.']",Viruses,,,True
fb24be7627ebce76ab2862e689432a8a0de11343,PMC,Regulation of Immunogen Processing: Signal Sequences and Their Application for the New Generation of DNA-Vaccines,,PMC3347541,22649628,CC BY,"Immunization with naked genes (DNA–immunization) is a perspective modern approach to prophylactic as well as therapeutic vaccination against pathogens, as well as cancer and allergy. A panel of DNA immunogens has been developed, some are already in the clinical trials. However, the immunogenicity of DNA vaccines, specifically of those applied to humans, needs a considerable improvement. There are several approaches to increase DNA vaccine immunogenicity. One approach implies the modifications of the encoded immunogen that change its processing and presentation, and thus the overall pattern of anti–immunogen response. For this, eukaryotic expression vectors are constructed that encode the chimeric proteins composed of the immunogen and specialized targeting or signal sequences. The review describes a number of signals that if fused to immunogen, target it into the predefined subcellular compartments. The review gives examples of their application for DNA–immunization.",2010 Apr,"['Starodubova, E.S.', 'Isaguliants, M.G.', 'Karpov, V.L.']",Acta Naturae,,,True
c62b68c066ad9cbdee5244b9b97e06d7286b2364,PMC,Chinese Medicine Shenfu Injection for Heart Failure: A Systematic Review and Meta-Analysis,http://dx.doi.org/10.1155/2012/713149,PMC3348640,22611430,CC BY,"Objective. Heart failure (HF) is a global public health problem. Early literature studies manifested that Shenfu injection (SFI) is one of the most commonly used traditional Chinese patent medicine for HF in China. This article intended to systematically evaluate the efficacy and safety of SFI for HF. Methods. An extensive search was performed within 6 English and Chinese electronic database up to November 2011. Ninety-nine randomized controlled trails (RCTs) were collected, irrespective of languages. Two authors extracted data and assessed the trial quality independently. RevMan 5.0.2 was used for data analysis. Results. Compared with routine treatment and/or device support, SFI combined with routine treatment and/or device support showed better effect on clinical effect rate, mortality, heart rate, NT-proBNP and 6-minute walk distance. Results in ultrasonic cardiography also showed that SFI combined with routine treatment improved heart function of HF patients. There were no significant difference in blood pressure between SFI and routine treatment groups. Adverse events were reported in thirteen trails with thirteen specific symptoms, while no serious adverse effect was reported. Conclusion. SFI appear to be effective for treating HF. However, further rigorously designed RCTs are warranted because of insufficient methodological rigor in the majority of included trials.",2012 Apr 24,"['Wen-Ting, Song', 'Fa-Feng, Cheng', 'Li, Xu', 'Cheng-Ren, Lin', 'Jian-Xun, Liu']",Evid Based Complement Alternat Med,,,True
f06dde80e1f11939bb7306853ca92a8c9382ede4,PMC,Prevalence and risk factors of feline leukaemia virus and feline immunodeficiency virus in peninsular Malaysia,http://dx.doi.org/10.1186/1746-6148-8-33,PMC3349470,22439903,CC BY,"BACKGROUND: Feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) are major causes of morbidity and mortality in domestic and wild felids. Despite the clinical importance of feline retroviruses and the growing interest in cats as pets, information about FeLV and FIV in Malaysia is presently insufficient to properly advise veterinarians and pet owners. A cross-sectional study was carried out from January 2010 to December 2010 to determine the prevalence and risk factors associated with FeLV and FIV among domestic cats in peninsular Malaysia. Plasma samples were harvested from the blood of 368 domestic cats and screened for evidence of FeLV p27 antigen and FIV antibodies, using an immunochromatographic kit. Additionally, data on cat demographics and health were collected using a structured questionnaire, and were evaluated as potential risk factors for FeLV or FIV status. RESULTS: Of the 368 cats that were evaluated in this study, 12.2% (45/368; 95% CI = 8.88 - 15.58) were positive for FeLV p27 antigen, 31.3%, (115/368; 95% CI = 26.51 - 35.99) were seropositive to FIV antibodies, and 4.3% (16/368; 95% CI = 2.27 - 6.43) had evidence of both viruses. Factors found to significantly increase the risk for FeLV seropositivity include sex, age, behaviour, sickness, and living in a multi-cat household. Seropositive response to FIV was significantly associated with sex, neuter status, age, behaviour, and health status. CONCLUSIONS: The present study indicates that FeLV and FIV are common among domestic cats in peninsular Malaysia, and that factors related to cat demographics and health such as age, sex, behaviour, health status and type of household are important predictors for seropositive status to FeLV or FIV in peninsular Malaysia. High prevalence of FeLV or FIV observed in our study is of concern, in view of the immunosuppressive potentials of the two pathogens. Specific measures for control and prevention such as screening and routine vaccination are needed to ensure that FeLV and FIV are controlled in the cat population of peninsular Malaysia.",2012 Mar 22,"['Bande, Faruku', 'Arshad, Siti Suri', 'Hassan, Latiffah', 'Zakaria, Zunita', 'Sapian, Nurul Asyikin', 'Rahman, Noor Alimah', 'Alazawy, Amer']",BMC Vet Res,,,True
31f33e2c73a467477e3a4a72e6ee128703946fe5,PMC,Factors influencing integration of TB services in general hospitals in two regions of China: a qualitative study,http://dx.doi.org/10.1186/1472-6963-12-21,PMC3349562,22276746,CC BY,"BACKGROUND: In the majority of China, the Centre for Disease Control (CDC) at the county level provides both clinical and public health care for TB cases, with hospitals and other health facilities referring suspected TB cases to the CDC. In recent years, an integrated model has emerged, where the CDC remains the basic management unit for TB control, while a general hospital is designated to provide clinical care for TB patients. This study aims to explore the factors that influence the integration of TB services in general hospitals and generate knowledge to aid the scale-up of integration of TB services in China. METHODS: This study adopted a qualitative approach using interviews from sites in East and West China. Analysis was conducted using a thematic framework approach. RESULTS: The more prosperous site in East China was more coordinated and thus had a better method of resource allocation and more patient-orientated service, compared with the poorer site in the West. The development of public health organizations appeared to influence how effectively integration occurred. An understanding from staff that hospitals had better capacity to treat TB patients than CDCs was a strong rationale for integration. However, the economic and political interests might act as a barrier to effective integration. Both sites shared the same challenges of attracting and retaining a skilled workforce for the TB services. The role of the health bureau was more directive in the Western site, while a more participatory and collaborative approach was adopted in the Eastern site. CONCLUSION: The process of integration identifies similarities and differences between sites in more affluent East China and poorer West China. Integration of TB services in the hospitals needs to address the challenges of stakeholder motivations and resource allocation. Effective inter-organizational collaboration could help to improve the efficiency and quality of TB service. Key words: TB control, service delivery, integration, hospitals, China.",2012 Jan 25,"['Zou, Guanyang', 'Wei, Xiaolin', 'Walley, John D', 'Yin, Jia', 'Sun, Qiang']",BMC Health Serv Res,,,True
cf3abd4ab4ea9d7d602482b62166463db3dffc02,PMC,A systematic review to identify areas of enhancements of pandemic simulation models for operational use at provincial and local levels,http://dx.doi.org/10.1186/1471-2458-12-251,PMC3350431,22463370,CC BY,"BACKGROUND: In recent years, computer simulation models have supported development of pandemic influenza preparedness policies. However, U.S. policymakers have raised several concerns about the practical use of these models. In this review paper, we examine the extent to which the current literature already addresses these concerns and identify means of enhancing the current models for higher operational use. METHODS: We surveyed PubMed and other sources for published research literature on simulation models for influenza pandemic preparedness. We identified 23 models published between 1990 and 2010 that consider single-region (e.g., country, province, city) outbreaks and multi-pronged mitigation strategies. We developed a plan for examination of the literature based on the concerns raised by the policymakers. RESULTS: While examining the concerns about the adequacy and validity of data, we found that though the epidemiological data supporting the models appears to be adequate, it should be validated through as many updates as possible during an outbreak. Demographical data must improve its interfaces for access, retrieval, and translation into model parameters. Regarding the concern about credibility and validity of modeling assumptions, we found that the models often simplify reality to reduce computational burden. Such simplifications may be permissible if they do not interfere with the performance assessment of the mitigation strategies. We also agreed with the concern that social behavior is inadequately represented in pandemic influenza models. Our review showed that the models consider only a few social-behavioral aspects including contact rates, withdrawal from work or school due to symptoms appearance or to care for sick relatives, and compliance to social distancing, vaccination, and antiviral prophylaxis. The concern about the degree of accessibility of the models is palpable, since we found three models that are currently accessible by the public while other models are seeking public accessibility. Policymakers would prefer models scalable to any population size that can be downloadable and operable in personal computers. But scaling models to larger populations would often require computational needs that cannot be handled with personal computers and laptops. As a limitation, we state that some existing models could not be included in our review due to their limited available documentation discussing the choice of relevant parameter values. CONCLUSIONS: To adequately address the concerns of the policymakers, we need continuing model enhancements in critical areas including: updating of epidemiological data during a pandemic, smooth handling of large demographical databases, incorporation of a broader spectrum of social-behavioral aspects, updating information for contact patterns, adaptation of recent methodologies for collecting human mobility data, and improvement of computational efficiency and accessibility.",2012 Mar 30,"['Prieto, Diana M', 'Das, Tapas K', 'Savachkin, Alex A', 'Uribe, Andres', 'Izurieta, Ricardo', 'Malavade, Sharad']",BMC Public Health,,,True
71a82ecd1070ef91422c1ed772c73ad189ea4c0e,PMC,De-Novo Transcriptome Sequencing of a Normalized cDNA Pool from Influenza Infected Ferrets,http://dx.doi.org/10.1371/journal.pone.0037104,PMC3350496,22606336,CC BY,"The ferret is commonly used as a model for studies of infectious diseases. The genomic sequence of this animal model is not yet characterized, and only a limited number of fully annotated cDNAs are currently available in GenBank. The majority of genes involved in innate or adaptive immune response are still lacking, restricting molecular genetic analysis of host response in the ferret model. To enable de novo identification of transcriptionally active ferret genes in response to infection, we performed de-novo transcriptome sequencing of animals infected with H1N1 A/California/07/2009. We also included splenocytes induced with bacterial lipopolysaccharide to allow for identification of transcripts specifically induced by Gram-negative bacteria. We pooled and normalized the cDNA library in order to delimit the risk of sequencing only highly expressed genes. While normalization of the cDNA library removes the possibility of assessing expression changes between individual animals, it has been shown to increase identification of low abundant transcripts. In this study, we identified more than 19000 partial ferret transcripts, including more than 1000 gene orthologs known to be involved in the innate and the adaptive immune response.",2012 May 11,"['Camp, Jeremy V.', 'Svensson, Thomas L.', 'McBrayer, Alexis', 'Jonsson, Colleen B.', 'Liljeström, Peter', 'Bruder, Carl E.']",PLoS One,,,True
bae589aad9c7fe95e859487dc9185968c54d584e,PMC,Interleukin-2 signalling is modulated by a labile disulfide bond in the CD132 chain of its receptor,http://dx.doi.org/10.1098/rsob.110036,PMC3352089,22645657,CC BY,"Certain disulfide bonds present in leucocyte membrane proteins are labile and can be reduced in inflammation. This can cause structural changes that result in downstream functional effects, for example, in integrin activation. Recent studies have shown that a wide range of membrane proteins have labile disulfide bonds including CD132, the common gamma chain of the receptors for several cytokines including interleukin-2 and interleukin-4 (IL-2 and IL-4). The Cys(183)–Cys(232) disulfide bond in mouse CD132 is susceptible to reduction by enzymes such as thioredoxin (TRX), gamma interferon-inducible lysosomal thiolreductase and protein disulfide isomerase, which are commonly secreted during immune activation. The Cys(183)–Cys(232) disulfide bond is also reduced in an in vivo lipopolysaccharide (LPS)-induced acute model of inflammation. Conditions that lead to the reduction of the Cys(183)–Cys(232) disulfide bond in CD132 inhibit proliferation of an IL-2-dependent T cell clone and concomitant inhibition of the STAT-5 signalling pathway. The same reducing conditions had no effect on the proliferation of an IL-2-independent T cell clone, nor did they reduce disulfide bonds in IL-2 itself. We postulate that reduction of the Cys(183)–Cys(232) disulfide in CD132 inhibits IL-2 binding to the receptor complex. Published data show that the Cys(183)–Cys(232) disulfide bond is exposed at the surface of CD132 and in close contact with IL-2 and IL-4 in their respective receptor complexes. In addition, mutants in these Cys residues in human CD132 lead to immunodeficiency and loss of IL-2 binding. These results have wider implications for the regulation of cytokine receptors in general, as their activity can be modulated by a ‘redox regulator’ mechanism caused by the changes in the redox environment that occur during inflammation and activation of the immune system.",2012 Jan,"['Metcalfe, Clive', 'Cresswell, Peter', 'Barclay, A. Neil']",Open Biol,,,True
562b04e742412e61bd4087a2a13734391a988a8f,PMC,A randomized open-label trial on the use of budesonide/formoterol (Symbicort(®)) as an alternative reliever medication for mild to moderate asthmatic attacks,http://dx.doi.org/10.1186/1865-1380-5-16,PMC3352303,22503137,CC BY,"BACKGROUND: Conventionally, a nebulized short-acting β-2 agonist like salbutamol is often used as the reliever in acute exacerbations of asthma. However, recent worldwide respiratory outbreaks discourage routine use of nebulization. Previous studies have shown that combined budesonide/formoterol (Symbicort(®), AstraZeneca) is effective as both a maintenance and reliever anti-asthmatic medication. METHODS: We performed a randomized, open-label study from March until August 2011 to compare the bronchodilatory effects of Symbicort(® )vs. nebulized salbutamol in acute exacerbation of mild to moderate asthmatic attack in an emergency department. Initial objective parameters measured include the oxygen saturation, peak expiratory flow rate (PEFR) and respiratory rate. During clinical reassessment, subjective parameters [i.e., Visual Analog Scale (VAS) and 5-point Likert scale of breathlessness] and the second reading of the objective parameters were measured. For the 5-point Likert scale, the patients were asked to describe their symptom relief as 1, much worse; 2, a little worse; 3, no change; 4, a little better; 5, much better. RESULTS: Out of the total of 32 patients enrolled, 17 patients (53%) were randomized to receive nebulized salbutamol and 15 (47%) to receive Symbicort(®). For both treatment arms, by using paired t- and Wilcoxon signed rank tests, it was shown that there were statistically significant improvements in oxygen saturation, PEFR and respiratory rate within the individual treatment groups (pre- vs. post-treatment). Comparing the effects of Symbicort(® )vs. nebulized salbutamol, the average improvement of oxygen saturation was 1% in both treatment arms (p = 0.464), PEFR 78.67 l/min vs. 89.41 l/min, respectively (p = 0.507), and respiratory rate 2/min vs. 2/min (p = 0.890). For subjective evaluation, all patients reported improvement in the VAS (average 2.45 cm vs. 2.20 cm), respectively (p = 0.765). All patients in both treatment arms reported either ""a little better"" or ""much better"" on the 5-point Likert scale, with none reporting ""no change"" or getting worse. CONCLUSION: This study suggests that there is no statistical difference between using Symbicort(® )vs. nebulized salbutamol as the reliever for the first 15 min post-intervention.",2012 Apr 13,"['Chew, Keng Sheng', 'Kamarudin, Hamizah', 'Hashim, Che Wan']",Int J Emerg Med,,,True
ac0ab279eea38eef425c76172c917fd896417d6c,PMC,The impact of CPR and AED training on healthcare professionals' self-perceived attitudes to performing resuscitation,http://dx.doi.org/10.1186/1757-7241-20-26,PMC3352321,22480164,CC BY,"BACKGROUND: Healthcare professionals have shown concern about performing mouth-to-mouth ventilation due to the risks to themselves with the procedure. However, little is known about healthcare professionals' fears and attitudes to start CPR and the impact of training. OBJECTIVE: To examine whether there were any changes in the attitudes among healthcare professionals to performing CPR from before to after training. METHODS: Healthcare professionals from two Swedish hospitals were asked to answer a questionnaire before and after training. The questions were relating to physical and mental discomfort and attitudes to CPR. Statistical analysis used was generalized McNemar's test. RESULTS: Overall, there was significant improvement in 10 of 11 items, reflecting various aspects of attitudes to CPR. All groups of health care professionals (physicians, nurses, assistant nurses, and ""others"" = physiotherapists, occupational therapists, social welfare officers, psychologists, biomedical analysts) felt more secure in CPR knowledge after education. In other aspects, such as anxiety prior to a possible cardiac arrest, only nurses and assistant nurses improved. The concern about being infected, when performing mouth to mouth ventilation, was reduced with the most marked reduction in physicians (75%; P < 0.001). CONCLUSION: In this hospital-based setting, we found a positive outcome of education and training in CPR concerning healthcare professionals' attitudes to perform CPR. They felt more secure in their knowledge of cardiopulmonary resuscitation. In some aspects of attitudes to resuscitation nurses and assistant nurses appeared to be the groups that were most markedly influenced. The concern of being infected by a disease was low.",2012 Apr 5,"['Källestedt, Marie-Louise Södersved', 'Berglund, Anders', 'Herlitz, Johan', 'Leppert, Jerzy', 'Enlund, Mats']",Scand J Trauma Resusc Emerg Med,,,True
50f6c72d60ef3ae2d2235da9a307942a3f6685fe,PMC,Mechanism of Nucleic Acid Unwinding by SARS-CoV Helicase,http://dx.doi.org/10.1371/journal.pone.0036521,PMC3352918,22615777,CC BY,"The non-structural protein 13 (nsp13) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is a helicase that separates double-stranded RNA (dsRNA) or DNA (dsDNA) with a 5′→3′ polarity, using the energy of nucleotide hydrolysis. We determined the minimal mechanism of helicase function by nsp13. We showed a clear unwinding lag with increasing length of the double-stranded region of the nucleic acid, suggesting the presence of intermediates in the unwinding process. To elucidate the nature of the intermediates we carried out transient kinetic analysis of the nsp13 helicase activity. We demonstrated that the enzyme unwinds nucleic acid in discrete steps of 9.3 base-pairs (bp) each, with a catalytic rate of 30 steps per second. Therefore the net unwinding rate is ∼280 base-pairs per second. We also showed that nsp12, the SARS-CoV RNA-dependent RNA polymerase (RdRp), enhances (2-fold) the catalytic efficiency of nsp13 by increasing the step size of nucleic acid (RNA/RNA or DNA/DNA) unwinding. This effect is specific for SARS-CoV nsp12, as no change in nsp13 activity was observed when foot-and-mouth-disease virus RdRp was used in place of nsp12. Our data provide experimental evidence that nsp13 and nsp12 can function in a concerted manner to improve the efficiency of viral replication and enhance our understanding of nsp13 function during SARS-CoV RNA synthesis.",2012 May 15,"['Adedeji, Adeyemi O.', 'Marchand, Bruno', 'te Velthuis, Aartjan J. W.', 'Snijder, Eric J.', 'Weiss, Susan', 'Eoff, Robert L.', 'Singh, Kamalendra', 'Sarafianos, Stefan G.']",PLoS One,,,True
f3e85a35ab89c9a55eeb83c6e17f881d5c497d82,PMC,Genome-wide host responses against infectious laryngotracheitis virus vaccine infection in chicken embryo lung cells,http://dx.doi.org/10.1186/1471-2164-13-143,PMC3353197,22530940,CC BY,"BACKGROUND: Infectious laryngotracheitis virus (ILTV; gallid herpesvirus 1) infection causes high mortality and huge economic losses in the poultry industry. To protect chickens against ILTV infection, chicken-embryo origin (CEO) and tissue-culture origin (TCO) vaccines have been used. However, the transmission of vaccine ILTV from vaccinated- to unvaccinated chickens can cause severe respiratory disease. Previously, host cell responses against virulent ILTV infections were determined by microarray analysis. In this study, a microarray analysis was performed to understand host-vaccine ILTV interactions at the host gene transcription level. RESULTS: The 44 K chicken oligo microarrays were used, and the results were compared to those found in virulent ILTV infection. Total RNAs extracted from vaccine ILTV infected chicken embryo lung cells at 1, 2, 3 and 4 days post infection (dpi), compared to 0 dpi, were subjected to microarray assay using the two color hybridization method. Data analysis using JMP Genomics 5.0 and the Ingenuity Pathway Analysis (IPA) program showed that 213 differentially expressed genes could be grouped into a number of functional categories including tissue development, cellular growth and proliferation, cellular movement, and inflammatory responses. Moreover, 10 possible gene networks were created by the IPA program to show intermolecular connections. Interestingly, of 213 differentially expressed genes, BMP2, C8orf79, F10, and NPY were expressed distinctly in vaccine ILTV infection when compared to virulent ILTV infection. CONCLUSIONS: Comprehensive knowledge of gene expression and biological functionalities of host factors during vaccine ILTV infection can provide insight into host cellular defense mechanisms compared to those of virulent ILTV.",2012 Apr 24,"['Lee, Jeongyoon', 'Bottje, Walter G', 'Kong, Byung-Whi']",BMC Genomics,,,True
a64792baacb18e3bbfb88eee3a3592c85f04a627,PMC,A Real-Time PCR Assay for Bat SARS-Like Coronavirus Detection and Its Application to Italian Greater Horseshoe Bat Faecal Sample Surveys,http://dx.doi.org/10.1100/2012/989514,PMC3353321,22654650,CC BY,"Bats are source of coronaviruses closely related to the severe acute respiratory syndrome (SARS) virus. Numerous studies have been carried out to identify new bat viruses related to SARS-coronavirus (bat-SARS-like CoVs) using a reverse-transcribed-polymerase chain reaction assay. However, a qualitative PCR could underestimate the prevalence of infection, affecting the epidemiological evaluation of bats in viral ecology. In this work an SYBR Green-real time PCR assay was developed for diagnosing infection with SARS-related coronaviruses from bat guano and was applied as screening tool in a survey carried out on 45 greater horseshoe bats (Rhinolophus ferrumequinum) sampled in Italy in 2009. The assay showed high sensitivity and reproducibility. Its application on bats screening resulted in a prevalence of 42%. This method could be suitable as screening tool in epidemiological surveys about the presence of bat-SARS-like CoVs, consequently to obtain a more realistic scenario of the viral prevalence in the population.",2011 Nov 22,"['Balboni, Andrea', 'Gallina, Laura', 'Palladini, Alessandra', 'Prosperi, Santino', 'Battilani, Mara']",ScientificWorldJournal,,,True
c916747a33f9b4a986dd0e4a4b853db6814b74f9,PMC,A General Strategy to Endow Natural Fusion-protein-Derived Peptides with Potent Antiviral Activity,http://dx.doi.org/10.1371/journal.pone.0036833,PMC3353973,22666328,CC BY,"Fusion between the viral and target cell membranes is an obligatory step for the infectivity of all enveloped virus, and blocking this process is a clinically validated therapeutic strategy. Viral fusion is driven by specialized proteins which, although specific to each virus, act through a common mechanism, the formation of a complex between two heptad repeat (HR) regions. The HR regions are initially separated in an intermediate termed “prehairpin”, which bridges the viral and cell membranes, and then fold onto each other to form a 6-helical bundle (6HB), driving the two membranes to fuse. HR-derived peptides can inhibit viral infectivity by binding to the prehairpin intermediate and preventing its transition to the 6HB. The antiviral activity of HR-derived peptides differs considerably among enveloped viruses. For weak inhibitors, potency can be increased by peptide engineering strategies, but sequence-specific optimization is time-consuming. In seeking ways to increase potency without changing the native sequence, we previously reported that attachment to the HR peptide of a cholesterol group (”cholesterol-tagging”) dramatically increases its antiviral potency, and simultaneously increases its half-life in vivo. We show here that antiviral potency may be increased by combining cholesterol-tagging with dimerization of the HR-derived sequence, using as examples human parainfluenza virus, Nipah virus, and HIV-1. Together, cholesterol-tagging and dimerization may represent strategies to boost HR peptide potency to levels that in some cases may be compatible with in vivo use, possibly contributing to emergency responses to outbreaks of existing or novel viruses.",2012 May 16,"['Pessi, Antonello', 'Langella, Annunziata', 'Capitò, Elena', 'Ghezzi, Silvia', 'Vicenzi, Elisa', 'Poli, Guido', 'Ketas, Thomas', 'Mathieu, Cyrille', 'Cortese, Riccardo', 'Horvat, Branka', 'Moscona, Anne', 'Porotto, Matteo']",PLoS One,,,True
154880a8053db7adb802ae5350656b649496b4a3,PMC,DC-SIGN (CD209) Promoter −336 A/G (rs4804803) Polymorphism Associated with Susceptibility of Kawasaki Disease,http://dx.doi.org/10.1100/2012/634835,PMC3354554,22629172,CC BY,"Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. High-dose intravenous immunoglobulin (IVIG) is the most effective therapy for KD to reduce the prevalence of coronary artery lesion (CAL) formation. Recently, the α2, 6 sialylated IgG was reported to interact with a lectin receptor, specific intracellular adhesion molecule-3 grabbing nonintegrin homolog-related 1 (SIGN-R1) in mice and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) in human, and to trigger an anti-inflammatory cascade. This study was conducted to investigate whether the polymorphism of DC-SIGN (CD209) promoter −336 A/G (rs4804803) is responsible for susceptibility and CAL formation in KD patients using Custom TaqMan SNP Genotyping Assays. A total of 521 subjects (278 KD patients and 243 controls) were investigated to identify an SNP of rs4804803, and they were studied and showed a significant association between the genotypes and allele frequency of rs4804803 in control subjects and KD patients (P = 0.004 under the dominant model). However, the promoter variant of DC-SIGN gene was not associated with the occurrence of IVIG resistance, CAL formation in KD. The G allele of DC-SIGN promoter −336 (rs4804803) is a risk allele in the development of KD.",2012 May 2,"['Yu, Hong-Ren', 'Chang, Wei-Pin', 'Wang, Lin', 'Lin, Ying-Jui', 'Liang, Chi-Di', 'Yang, Kuender D.', 'Kuo, Chiu-Ming', 'Huang, Yi-Chuan', 'Chang, Wei-Chiao', 'Kuo, Ho-Chang']",ScientificWorldJournal,,,True
704daa0a70b4f0c0ba3c8f723b27396877dca38b,PMC,CD40 Gene Polymorphisms Associated with Susceptibility and Coronary Artery Lesions of Kawasaki Disease in the Taiwanese Population,http://dx.doi.org/10.1100/2012/520865,PMC3354684,22645426,CC BY,"Background. Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. Our previous studies showed expression of CD40 ligand on CD4+ T cells correlated to the coronary artery lesion (CAL) and disease progress in KD. Other studies from Japan suggested the role of CD40L in the pathogenesis of CAL, and this might help explain the excessive number of males affected with KD but cannot be reproduced by Taiwanese population. This study was conducted to investigate the CD40 polymorphism in KD and CAL formation. Methods. A total of 950 subjects (381 KD patients and 569 controls) were investigated to identify 2 tagging single-nucleotide polymorphisms (tSNPs) of CD40 (rs4810485 and rs1535045) by using the TaqMan allelic discrimination assay. Results. A significant association was noted with regards to CD40 tSNPs (rs1535045) between controls and KD patients (P = 0.0405, dominant model). In KD patients, polymorphisms of CD40 (rs4810485) showed significant association with CAL formation (P = 0.0436, recessive model). Haplotype analysis did not yield more significant results between polymorphisms of CD40 and susceptibility/disease activity of KD. Conclusions. This study showed for the first time that polymorphisms of CD40 are associated with susceptibility to KD and CAL formation, in the Taiwanese population.",2012 May 2,"['Kuo, Ho-Chang', 'Chao, Mei-Chyn', 'Hsu, Yu-Wen', 'Lin, Ying-Chi', 'Huang, Ying-Hsien', 'Yu, Hong-Ren', 'Hou, Ming-Feng', 'Liang, Chi-Di', 'Yang, Kuender D.', 'Chang, Wei-Chiao', 'Wang, Chih-Lu']",ScientificWorldJournal,,,True
05eae269e7bd3b7b841a84c02b1c13a670faf012,PMC,The Ubiquitin/Proteasome System Mediates Entry and Endosomal Trafficking of Kaposi's Sarcoma-Associated Herpesvirus in Endothelial Cells,http://dx.doi.org/10.1371/journal.ppat.1002703,PMC3355089,22615563,CC BY,"Ubiquitination, a post-translational modification, mediates diverse cellular functions including endocytic transport of molecules. Kaposi's sarcoma-associated herpesvirus (KSHV), an enveloped herpesvirus, enters endothelial cells primarily through clathrin-mediated endocytosis. Whether ubiquitination and proteasome activity regulates KSHV entry and endocytosis remains unknown. We showed that inhibition of proteasome activity reduced KSHV entry into endothelial cells and intracellular trafficking to nuclei, thus preventing KSHV infection of the cells. Three-dimensional (3-D) analyses revealed accumulation of KSHV particles in a cytoplasmic compartment identified as EEA1+ endosomal vesicles upon proteasome inhibition. KSHV particles are colocalized with ubiquitin-binding proteins epsin and eps15. Furthermore, ubiquitination mediates internalization of both KSHV and one of its receptors integrin β1. KSHV particles are colocalized with activated forms of the E3 ligase c-Cbl. Knock-down of c-Cbl or inhibition of its phosphorylation reduced viral entry and intracellular trafficking, resulting in decreased KSHV infectivity. These results demonstrate that ubiquitination mediates internalization of both KSHV and one of its cognate receptors integrin β1, and identify c-Cbl as a potential E3 ligase that facilitates this process.",2012 May 17,"['Greene, Whitney', 'Zhang, Wei', 'He, Meilan', 'Witt, Colleen', 'Ye, Fengchun', 'Gao, Shou-Jiang']",PLoS Pathog,,,True
9f3ce3644f26781fd3d232942e4b5a36291545b0,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,True
4a94e577fa3d124b70c4734955c91f78fe749993,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,False
2307b2dca802e80426f5ea0026fa5932ff391320,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,False
96eadfbd199d90264168e4ba9009f53259f395be,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,False
0c4b472760655e118f62a389b8208dc724eceab1,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,False
2e2c403d16452b2a2cb0898a7c2fd98f053bc138,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,False
22b1fb1eb3368bf9325c0ee8f8360bf90a68873f,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,False
a1789943e5bf551cedec49e4cbb52a0882b69ea4,PMC,Interferon-Induced Ifit2/ISG54 Protects Mice from Lethal VSV Neuropathogenesis,http://dx.doi.org/10.1371/journal.ppat.1002712,PMC3355090,22615570,CC BY,"Interferon protects mice from vesicular stomatitis virus (VSV) infection and pathogenesis; however, it is not known which of the numerous interferon-stimulated genes (ISG) mediate the antiviral effect. A prominent family of ISGs is the interferon-induced with tetratricopeptide repeats (Ifit) genes comprising three members in mice, Ifit1/ISG56, Ifit2/ISG54 and Ifit3/ISG49. Intranasal infection with a low dose of VSV is not lethal to wild-type mice and all three Ifit genes are induced in the central nervous system of the infected mice. We tested their potential contributions to the observed protection of wild-type mice from VSV pathogenesis, by taking advantage of the newly generated knockout mice lacking either Ifit2 or Ifit1. We observed that in Ifit2 knockout (Ifit2 (−/−)) mice, intranasal VSV infection was uniformly lethal and death was preceded by neurological signs, such as ataxia and hind limb paralysis. In contrast, wild-type and Ifit1 (−/−) mice were highly protected and survived without developing such disease. However, when VSV was injected intracranially, virus replication and survival were not significantly different between wild-type and Ifit2(−/−) mice. When administered intranasally, VSV entered the central nervous system through the olfactory bulbs, where it replicated equivalently in wild-type and Ifit2 (−/−) mice and induced interferon-β. However, as the infection spread to other regions of the brain, VSV titers rose several hundred folds higher in Ifit2 (−/−) mice as compared to wild-type mice. This was not caused by a broadened cell tropism in the brains of Ifit2 (−/−) mice, where VSV still replicated selectively in neurons. Surprisingly, this advantage for VSV replication in the brains of Ifit2(−/−) mice was not observed in other organs, such as lung and liver. Pathogenesis by another neurotropic RNA virus, encephalomyocarditis virus, was not enhanced in the brains of Ifit2 (−/−) mice. Our study provides a clear demonstration of tissue-, virus- and ISG-specific antiviral action of interferon.",2012 May 17,"['Fensterl, Volker', 'Wetzel, Jaime L.', 'Ramachandran, Srividya', 'Ogino, Tomoaki', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.', 'Diamond, Michael S.', 'Virgin, Herbert W.', 'Sen, Ganes C.']",PLoS Pathog,,,False
48346dec8180ad8bc1f1bcab9fb95f52d13c920f,PMC,CD200 Receptor Controls Sex-Specific TLR7 Responses to Viral Infection,http://dx.doi.org/10.1371/journal.ppat.1002710,PMC3355091,22615569,CC BY,"Immunological checkpoints, such as the inhibitory CD200 receptor (CD200R), play a dual role in balancing the immune system during microbial infection. On the one hand these inhibitory signals prevent excessive immune mediated pathology but on the other hand they may impair clearance of the pathogen. We studied the influence of the inhibitory CD200-CD200R axis on clearance and pathology in two different virus infection models. We find that lack of CD200R signaling strongly enhances type I interferon (IFN) production and viral clearance and improves the outcome of mouse hepatitis corona virus (MHV) infection, particularly in female mice. MHV clearance is known to be dependent on Toll like receptor 7 (TLR7)-mediated type I IFN production and sex differences in TLR7 responses previously have been reported for humans. We therefore hypothesize that CD200R ligation suppresses TLR7 responses and that release of this inhibition enlarges sex differences in TLR7 signaling. This hypothesis is supported by our findings that in vivo administration of synthetic TLR7 ligand leads to enhanced type I IFN production, particularly in female Cd200(−/−) mice and that CD200R ligation inhibits TLR7 signaling in vitro. In influenza A virus infection we show that viral clearance is determined by sex but not by CD200R signaling. However, absence of CD200R in influenza A virus infection results in enhanced lung neutrophil influx and pathology in females. Thus, CD200-CD200R and sex are host factors that together determine the outcome of viral infection. Our data predict a sex bias in both beneficial and pathological immune responses to virus infection upon therapeutic targeting of CD200-CD200R.",2012 May 17,"['Karnam, Guruswamy', 'Rygiel, Tomasz P.', 'Raaben, Matthijs', 'Grinwis, Guy C. M.', 'Coenjaerts, Frank E.', 'Ressing, Maaike E.', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.', 'Meyaard, Linde']",PLoS Pathog,,,True
dc6666eb8156bd4638809009f795ebd4a7843569,PMC,Immunogenetic Mechanisms Driving Norovirus GII.4 Antigenic Variation,http://dx.doi.org/10.1371/journal.ppat.1002705,PMC3355092,22615565,CC BY,"Noroviruses are the principal cause of epidemic gastroenteritis worldwide with GII.4 strains accounting for 80% of infections. The major capsid protein of GII.4 strains is evolving rapidly, resulting in new epidemic strains with altered antigenic potentials. To test if antigenic drift may contribute to GII.4 persistence, human memory B cells were immortalized and the resulting human monoclonal antibodies (mAbs) characterized for reactivity to a panel of time-ordered GII.4 virus-like particles (VLPs). Reflecting the complex exposure history of the volunteer, human anti-GII.4 mAbs grouped into three VLP reactivity patterns; ancestral (1987–1997), contemporary (2004–2009), and broad (1987–2009). NVB 114 reacted exclusively to the earliest GII.4 VLPs by EIA and blockade. NVB 97 specifically bound and blocked only contemporary GII.4 VLPs, while NBV 111 and 43.9 exclusively reacted with and blocked variants of the GII.4.2006 Minerva strain. Three mAbs had broad GII.4 reactivity. Two, NVB 37.10 and 61.3, also detected other genogroup II VLPs by EIA but did not block any VLP interactions with carbohydrate ligands. NVB 71.4 cross-neutralized the panel of time-ordered GII.4 VLPs, as measured by VLP-carbohydrate blockade assays. Using mutant VLPs designed to alter predicted antigenic epitopes, two evolving, GII.4-specific, blockade epitopes were mapped. Amino acids 294–298 and 368–372 were required for binding NVB 114, 111 and 43.9 mAbs. Amino acids 393–395 were essential for binding NVB 97, supporting earlier correlations between antibody blockade escape and carbohydrate binding variation. These data inform VLP vaccine design, provide a strategy for expanding the cross-blockade potential of chimeric VLP vaccines, and identify an antibody with broadly neutralizing therapeutic potential for the treatment of human disease. Moreover, these data support the hypothesis that GII.4 norovirus evolution is heavily influenced by antigenic variation of neutralizing epitopes and consequently, antibody-driven receptor switching; thus, protective herd immunity is a driving force in norovirus molecular evolution.",2012 May 17,"['Lindesmith, Lisa C.', 'Beltramello, Martina', 'Donaldson, Eric F.', 'Corti, Davide', 'Swanstrom, Jesica', 'Debbink, Kari', 'Lanzavecchia, Antonio', 'Baric, Ralph S.']",PLoS Pathog,,,True
095a46646955ce130f476cabd654f8bd1c0f2cf4,PMC,Immunogenetic Mechanisms Driving Norovirus GII.4 Antigenic Variation,http://dx.doi.org/10.1371/journal.ppat.1002705,PMC3355092,22615565,CC BY,"Noroviruses are the principal cause of epidemic gastroenteritis worldwide with GII.4 strains accounting for 80% of infections. The major capsid protein of GII.4 strains is evolving rapidly, resulting in new epidemic strains with altered antigenic potentials. To test if antigenic drift may contribute to GII.4 persistence, human memory B cells were immortalized and the resulting human monoclonal antibodies (mAbs) characterized for reactivity to a panel of time-ordered GII.4 virus-like particles (VLPs). Reflecting the complex exposure history of the volunteer, human anti-GII.4 mAbs grouped into three VLP reactivity patterns; ancestral (1987–1997), contemporary (2004–2009), and broad (1987–2009). NVB 114 reacted exclusively to the earliest GII.4 VLPs by EIA and blockade. NVB 97 specifically bound and blocked only contemporary GII.4 VLPs, while NBV 111 and 43.9 exclusively reacted with and blocked variants of the GII.4.2006 Minerva strain. Three mAbs had broad GII.4 reactivity. Two, NVB 37.10 and 61.3, also detected other genogroup II VLPs by EIA but did not block any VLP interactions with carbohydrate ligands. NVB 71.4 cross-neutralized the panel of time-ordered GII.4 VLPs, as measured by VLP-carbohydrate blockade assays. Using mutant VLPs designed to alter predicted antigenic epitopes, two evolving, GII.4-specific, blockade epitopes were mapped. Amino acids 294–298 and 368–372 were required for binding NVB 114, 111 and 43.9 mAbs. Amino acids 393–395 were essential for binding NVB 97, supporting earlier correlations between antibody blockade escape and carbohydrate binding variation. These data inform VLP vaccine design, provide a strategy for expanding the cross-blockade potential of chimeric VLP vaccines, and identify an antibody with broadly neutralizing therapeutic potential for the treatment of human disease. Moreover, these data support the hypothesis that GII.4 norovirus evolution is heavily influenced by antigenic variation of neutralizing epitopes and consequently, antibody-driven receptor switching; thus, protective herd immunity is a driving force in norovirus molecular evolution.",2012 May 17,"['Lindesmith, Lisa C.', 'Beltramello, Martina', 'Donaldson, Eric F.', 'Corti, Davide', 'Swanstrom, Jesica', 'Debbink, Kari', 'Lanzavecchia, Antonio', 'Baric, Ralph S.']",PLoS Pathog,,,False
226a0c0674dd9f9ad4a4e90ff6f03decb03457ab,PMC,Induction of GADD34 Is Necessary for dsRNA-Dependent Interferon-β Production and Participates in the Control of Chikungunya Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1002708,PMC3355096,22615568,CC BY,"Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events. The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2α) and inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN and other cytokines. We demonstrate that the phosphatase-1 cofactor, growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), an important component of the unfolded protein response (UPR), is absolutely required for type I-IFN and IL-6 production by mouse embryonic fibroblasts (MEFs) in response to dsRNA. GADD34 expression in MEFs is dependent on PKR activation, linking cytosolic microbial sensing with the ATF4 branch of the UPR. The importance of this link for anti-viral immunity is underlined by the extreme susceptibility of GADD34-deficient fibroblasts and neonate mice to Chikungunya virus infection.",2012 May 17,"['Clavarino, Giovanna', 'Cláudio, Nuno', 'Couderc, Thérèse', 'Dalet, Alexandre', 'Judith, Delphine', 'Camosseto, Voahirana', 'Schmidt, Enrico K.', 'Wenger, Till', 'Lecuit, Marc', 'Gatti, Evelina', 'Pierre, Philippe']",PLoS Pathog,,,True
eff3310317521aed7abe06ef1fa9963ca9d6caf3,PMC,The Adjuvanticity of an O. volvulus-Derived rOv-ASP-1 Protein in Mice Using Sequential Vaccinations and in Non-Human Primates,http://dx.doi.org/10.1371/journal.pone.0037019,PMC3355165,22615877,CC BY,"Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant.",2012 May 17,"['Wang, Jing', 'Tricoche, Nancy', 'Du, Lanying', 'Hunter, Meredith', 'Zhan, Bin', 'Goud, Gaddam', 'Didier, Elizabeth S.', 'Liu, Jing', 'Lu, Lu', 'Marx, Preston A.', 'Jiang, Shibo', 'Lustigman, Sara']",PLoS One,,,True
ff218f343fbca258501ba42368ecbb57660e5a8f,PMC,An Analogue of the Antibiotic Teicoplanin Prevents Flavivirus Entry In Vitro,http://dx.doi.org/10.1371/journal.pone.0037244,PMC3356272,22624001,CC BY,"There is an urgent need for potent inhibitors of dengue virus (DENV) replication for the treatment and/or prophylaxis of infections with this virus. We here report on an aglycon analogue of the antibiotic teicoplanin (code name LCTA-949) that inhibits DENV-induced cytopathic effect (CPE) in a dose-dependent manner. Virus infection was completely inhibited at concentrations that had no adverse effect on the host cells. These findings were corroborated by quantification of viral RNA levels in culture supernatant. Antiviral activity was also observed against other flaviviruses such as the yellow fever virus and the tick-borne encephalitis virus (TBEV). In particular, potent antiviral activity was observed against TBEV. Time-of-drug-addition experiments indicated that LCTA-949 inhibits an early stage in the DENV replication cycle; however, a virucidal effect was excluded. This observation was corroborated by the fact that LCTA-949 lacks activity on DENV subgenomic replicon (that does not encode structural proteins) replication. Using a microsopy-based binding and fusion assay employing DiD-labeled viruses, it was shown that LCTA-949 targets the early stage (binding/entry) of the infection. Moreover, LCTA-949 efficiently inhibits infectivity of DENV particles pre-opsonized with antibodies, thus potentially also inhibiting antibody-dependent enhancement (ADE). In conclusion, LCTA-949 exerts in vitro activity against several flaviviruses and does so (as shown for DENV) by interfering with an early step in the viral replication cycle.",2012 May 18,"['De Burghgraeve, Tine', 'Kaptein, Suzanne J. F.', 'Ayala-Nunez, Nilda V.', 'Mondotte, Juan A.', 'Pastorino, Boris', 'Printsevskaya, Svetlana S.', 'de Lamballerie, Xavier', 'Jacobs, Michael', 'Preobrazhenskaya, Maria', 'Gamarnik, Andrea V.', 'Smit, Jolanda M.', 'Neyts, Johan']",PLoS One,,,True
2a423f15be9162d939e0402df6f74c31ee2e9486,PMC,Viral Infection in Renal Transplant Recipients,http://dx.doi.org/10.1100/2012/820621,PMC3357934,22654630,CC BY,"Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens.",2012 May 2,"['Cukuranovic, Jovana', 'Ugrenovic, Sladjana', 'Jovanovic, Ivan', 'Visnjic, Milan', 'Stefanovic, Vladisav']",ScientificWorldJournal,,,True
a466d42cb39e44cacc9d9923ddf169e6a9dad838,PMC,The Time Required to Estimate the Case Fatality Ratio of Influenza Using Only the Tip of an Iceberg: Joint Estimation of the Virulence and the Transmission Potential,http://dx.doi.org/10.1155/2012/978901,PMC3357941,22649483,CC BY,"Estimating the case fatality ratio (CFR) of a novel strain of influenza virus during the early stage of the pandemic is one of key epidemiological tasks to be conducted as rapid research response. Past experience during the epidemics of severe acute respiratory syndrome (SARS) and influenza A (H1N1-2009) posed several technical challenges in estimating the CFR in real time. The present study aimed to develop a simple method to estimate the CFR based on readily available datasets, that is, confirmed cases and deaths, while addressing some of the known technical issues. To assess the reliability and validity of the proposed method, we examined the minimum length of time required for the assigned CFR to be included within the 95% confidence intervals and for the estimated CFR to be below a prespecified cut-off value by means of Monte Carlo simulations. Overall, the smaller the transmission potential was, the longer it took to compare the estimated CFR against the cut-off value. If policymaking and public health response have to be made based on the CFR estimate derived from the proposed method and readily available data, it should be noted that the successful estimation may take longer than a few months.",2012 May 10,"['Ejima, Keisuke', 'Omori, Ryosuke', 'Cowling, Benjamin J.', 'Aihara, Kazuyuki', 'Nishiura, Hiroshi']",Comput Math Methods Med,,,True
cccb1a743e85a745309415410b3101c2ab1b59bb,PMC,Increased Urinary Angiotensin-Converting Enzyme 2 in Renal Transplant Patients with Diabetes,http://dx.doi.org/10.1371/journal.pone.0037649,PMC3358292,22629438,CC BY,"Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme, since it converts angiotensin (Ang) II to Ang-(1-7). ACE2 has been detected in urine from patients with chronic kidney disease. We measured urinary ACE2 activity and protein levels in renal transplant patients (age 54 yrs, 65% male, 38% diabetes, n = 100) and healthy controls (age 45 yrs, 26% male, n = 50), and determined factors associated with elevated urinary ACE2 in the patients. Urine from transplant subjects was also assayed for ACE mRNA and protein. No subjects were taking inhibitors of the renin-angiotensin system. Urinary ACE2 levels were significantly higher in transplant patients compared to controls (p = 0.003 for ACE2 activity, and p≤0.001 for ACE2 protein by ELISA or western analysis). Transplant patients with diabetes mellitus had significantly increased urinary ACE2 activity and protein levels compared to non-diabetics (p<0.001), while ACE2 mRNA levels did not differ. Urinary ACE activity and protein were significantly increased in diabetic transplant subjects, while ACE mRNA levels did not differ from non-diabetic subjects. After adjusting for confounding variables, diabetes was significantly associated with urinary ACE2 activity (p = 0.003) and protein levels (p<0.001), while female gender was associated with urinary mRNA levels for both ACE2 and ACE. These data indicate that urinary ACE2 is increased in renal transplant recipients with diabetes, possibly due to increased shedding from tubular cells. Urinary ACE2 could be a marker of renal renin-angiotensin system activation in these patients.",2012 May 22,"['Xiao, Fengxia', 'Hiremath, Swapnil', 'Knoll, Greg', 'Zimpelmann, Joseph', 'Srivaratharajah, Kajenny', 'Jadhav, Deepak', 'Fergusson, Dean', 'Kennedy, Chris R. J.', 'Burns, Kevin D.']",PLoS One,,,True
0943374130f5f8474d6d480d4d038615a0e36de3,PMC,Interferon-α Improves Phosphoantigen-Induced Vγ9Vδ2 T-Cells Interferon-γ Production during Chronic HCV Infection,http://dx.doi.org/10.1371/journal.pone.0037014,PMC3358305,22629350,CC BY,"In chronic HCV infection, treatment failure and defective host immune response highly demand improved therapy strategies. Vγ9Vδ2 T-cells may inhibit HCV replication in vitro through IFN-γ release after Phosphoantigen (PhAg) stimulation. The aim of our work was to analyze Vγ9Vδ2 T-cell functionality during chronic HCV infection, studying the role of IFN-α on their function capability. IFN-γ production by Vγ9Vδ2 T-cells was analyzed in vitro in 24 HCV-infected patients and 35 healthy donors (HD) after PhAg stimulation with or without IFN-α. The effect of in vivo PhAg/IFN-α administration on plasma IFN-γ levels was analyzed in M. fascicularis monkeys. A quantitative analysis of IFN-γ mRNA level and stability in Vγ9Vδ2 T-cells was also evaluated. During chronic HCV infection, Vγ9Vδ2 T-cells showed an effector/activated phenotype and were significantly impaired in IFN-γ production. Interestingly, IFN-α was able to improve their IFN-γ response to PhAg both in vitro in HD and HCV-infected patients, and in vivo in Macaca fascicularis primates. Finally, IFN-α increased IFN-γ-mRNA transcription and stability in PhAg-activated Vγ9Vδ2 T-cells. Altogether our results show a functional impairment of Vγ9Vδ2 T-cells during chronic HCV infection that can be partially restored by using IFN-α. A study aimed to evaluate the antiviral impact of PhAg/IFN-α combination may provide new insight in designing possible combined strategies to improve HCV infection treatment outcome.",2012 May 22,"['Cimini, Eleonora', 'Bonnafous, Cécile', 'Bordoni, Veronica', 'Lalle, Eleonora', 'Sicard, Helene', 'Sacchi, Alessandra', 'Berno, Giulia', 'Gioia, Cristiana', 'D’Offizi, Gianpiero', 'Visco Comandini, Ubaldo', 'Vlassi, Chrysoula', 'Capobianchi, Maria Rosaria', 'Martini, Federico', 'Agrati, Chiara']",PLoS One,,,True
bbc89603600968ee09dd4b38c91616f83f7e0bba,PMC,West Nile Virus Infection Causes Endocytosis of a Specific Subset of Tight Junction Membrane Proteins,http://dx.doi.org/10.1371/journal.pone.0037886,PMC3359987,22655077,CC BY,"West Nile virus (WNV) is a blood-borne pathogen that causes systemic infections and serious neurological disease in human and animals. The most common route of infection is mosquito bites and therefore, the virus must cross a number of polarized cell layers to gain access to organ tissue and the central nervous system. Resistance to trans-cellular movement of macromolecules between epithelial and endothelial cells is mediated by tight junction complexes. While a number of recent studies have documented that WNV infection negatively impacts the barrier function of tight junctions, the intracellular mechanism by which this occurs is poorly understood. In the present study, we report that endocytosis of a subset of tight junction membrane proteins including claudin-1 and JAM-1 occurs in WNV infected epithelial and endothelial cells. This process, which ultimately results in lysosomal degradation of the proteins, is dependent on the GTPase dynamin and microtubule-based transport. Finally, infection of polarized cells with the related flavivirus, Dengue virus-2, did not result in significant loss of tight junction membrane proteins. These results suggest that neurotropic flaviviruses such as WNV modulate the host cell environment differently than hemorrhagic flaviviruses and thus may have implications for understanding the molecular basis for neuroinvasion.",2012 May 24,"['Xu, Zaikun', 'Waeckerlin, Regula', 'Urbanowski, Matt D.', 'van Marle, Guido', 'Hobman, Tom C.']",PLoS One,,,True
03d40dcd5d29728439528bd955afcba42bc0c2b9,PMC,"The Epitope and Neutralization Mechanism of AVFluIgG01, a Broad-Reactive Human Monoclonal Antibody against H5N1 Influenza Virus",http://dx.doi.org/10.1371/journal.pone.0038126,PMC3360650,22662275,CC BY,"The continued spread of highly pathogenic avian influenza (HPAI) H5N1 virus underscores the importance of effective antiviral approaches. AVFluIgG01 is a potent and broad-reactive H5N1-neutralizing human monoclonal antibody (mAb) showing great potential for use either for therapeutic purposes or as a basis of vaccine development, but its antigenic epitope and neutralization mechanism have not been finely characterized. In this study, we first demonstrated that AVFluIgG01 targets a novel conformation-dependent epitope in the globular head region of H5N1 hemagglutinin (HA). By selecting mimotopes from a random peptide library in combination with computational algorithms and site-directed mutagenesis, the epitope was mapped to three conserved discontinuous sites (I-III) that are located closely at the three-dimensional structure of HA. Further, we found that this HA1-specific human mAb can efficiently block both virus-receptor binding and post-attachment steps, while its Fab fragment exerts the post-attachment inhibition only. Consistently, AVFluIgG01 could inhibit HA-mediated cell-cell membrane fusion at a dose-dependent manner and block the acquisition of pH-induced protease sensitivity. These results suggest a neutralization mechanism of AVFluIgG01 by simultaneously blocking viral attachment to the receptors on host cells and interfering with HA conformational rearrangements associated with membrane fusion. The presented data provide critical information for developing novel antiviral therapeutics and vaccines against HPAI H5N1 virus.",2012 May 25,"['Cao, Zhiliang', 'Meng, Jiazi', 'Li, Xingxing', 'Wu, Ruiping', 'Huang, Yanxin', 'He, Yuxian']",PLoS One,,,True
b48c4779aeb4c5d68971cc74ac6e6974d39d9195,PMC,PepMapper: A Collaborative Web Tool for Mapping Epitopes from Affinity-Selected Peptides,http://dx.doi.org/10.1371/journal.pone.0037869,PMC3360666,22701536,CC BY,"Epitope mapping from affinity-selected peptides has become popular in epitope prediction, and correspondingly many Web-based tools have been developed in recent years. However, the performance of these tools varies in different circumstances. To address this problem, we employed an ensemble approach to incorporate two popular Web tools, MimoPro and Pep-3D-Search, together for taking advantages offered by both methods so as to give users more options for their specific purposes of epitope-peptide mapping. The combined operation of Union finds as many associated peptides as possible from both methods, which increases sensitivity in finding potential epitopic regions on a given antigen surface. The combined operation of Intersection achieves to some extent the mutual verification by the two methods and hence increases the likelihood of locating the genuine epitopic region on a given antigen in relation to the interacting peptides. The Consistency between Intersection and Union is an indirect sufficient condition to assess the likelihood of successful peptide-epitope mapping. On average from 27 tests, the combined operations of PepMapper outperformed either MimoPro or Pep-3D-Search alone. Therefore, PepMapper is another multipurpose mapping tool for epitope prediction from affinity-selected peptides. The Web server can be freely accessed at: http://informatics.nenu.edu.cn/PepMapper/",2012 May 25,"['Chen, Wenhan', 'Guo, William W.', 'Huang, Yanxin', 'Ma, Zhiqiang']",PLoS One,,,True
09340528717039c904847d959dd4ff0adcc308ed,PMC,Autophagy: More Than a Nonselective Pathway,http://dx.doi.org/10.1155/2012/219625,PMC3362037,22666256,CC BY,"Autophagy is a catabolic pathway conserved among eukaryotes that allows cells to rapidly eliminate large unwanted structures such as aberrant protein aggregates, superfluous or damaged organelles, and invading pathogens. The hallmark of this transport pathway is the sequestration of the cargoes that have to be degraded in the lysosomes by double-membrane vesicles called autophagosomes. The key actors mediating the biogenesis of these carriers are the autophagy-related genes (ATGs). For a long time, it was assumed that autophagy is a bulk process. Recent studies, however, have highlighted the capacity of this pathway to exclusively eliminate specific structures and thus better fulfil the catabolic necessities of the cell. We are just starting to unveil the regulation and mechanism of these selective types of autophagy, but what it is already clearly emerging is that structures targeted to destruction are accurately enwrapped by autophagosomes through the action of specific receptors and adaptors. In this paper, we will briefly discuss the impact that the selective types of autophagy have had on our understanding of autophagy.",2012 May 15,"['Reggiori, Fulvio', 'Komatsu, Masaaki', 'Finley, Kim', 'Simonsen, Anne']",Int J Cell Biol,,,True
24c20b8ab487acad45bb797b2ae0a2a910b31043,PMC,Eicosanoids and Respiratory Viral Infection: Coordinators of Inflammation and Potential Therapeutic Targets,http://dx.doi.org/10.1155/2012/236345,PMC3362132,22665949,CC BY,"Viruses are frequent causes of respiratory infection, and viral respiratory infections are significant causes of hospitalization, morbidity, and sometimes mortality in a variety of patient populations. Lung inflammation induced by infection with common respiratory pathogens such as influenza and respiratory syncytial virus is accompanied by increased lung production of prostaglandins and leukotrienes, lipid mediators with a wide range of effects on host immune function. Deficiency or pharmacologic inhibition of prostaglandin and leukotriene production often results in a dampened inflammatory response to acute infection with a respiratory virus. These mediators may, therefore, serve as appealing therapeutic targets for disease caused by respiratory viral infection.",2012 May 15,"['McCarthy, Mary K.', 'Weinberg, Jason B.']",Mediators Inflamm,,,True
826d74c66a4c9bf882880d1dccc50690c8cdaffb,PMC,Seroepidemiology of Human Bocavirus Infection in Jamaica,http://dx.doi.org/10.1371/journal.pone.0038206,PMC3362556,22666484,CC BY,"BACKGROUND: Human bocavirus (HBoV) is a newly identified human parvovirus. HBoV is associated with upper and lower respiratory tract infections and gastroenteritis in children. Little is known about the seroepidemiology of HBoV in populations in the Caribbean. METHODS: In a cross-sectional study conducted at the University Hospital of the West Indies in Kingston, Jamaica, 287 blood samples were collected from pediatric patients and tested for the presence of HBoV-specific antibody using a virus-like-particle based enzyme-linked immunosorbent assay (ELISA). RESULTS: HBoV-specific antibodies were found to be present in 220/287 (76.7%) of samples collected from the pediatric population. Seroprevalence of HBoV was highest in those ≥2 years old. The seroepidemiological profile suggests that most children are exposed to HBoV during the first two years of life in Jamaica. CONCLUSION: HBoV infection is common in children in Jamaica. HBoV seroprevalence rates in the Caribbean are similar to those previously reported in other areas of the world.",2012 May 29,"['Hustedt, Joshua W.', 'Christie, Celia', 'Hustedt, Madison M.', 'Esposito, Daina', 'Vazquez, Marietta']",PLoS One,,,True
86431a5391ad8d12589fe686d0486cf2a0e912f0,PMC,The Sigma Class Glutathione Transferase from the Liver Fluke Fasciola hepatica,http://dx.doi.org/10.1371/journal.pntd.0001666,PMC3362645,22666515,CC BY,"BACKGROUND: Liver fluke infection of livestock causes economic losses of over US$ 3 billion worldwide per annum. The disease is increasing in livestock worldwide and is a re-emerging human disease. There are currently no commercial vaccines, and only one drug with significant efficacy against adult worms and juveniles. A liver fluke vaccine is deemed essential as short-lived chemotherapy, which is prone to resistance, is an unsustainable option in both developed and developing countries. Protein superfamilies have provided a number of leading liver fluke vaccine candidates. A new form of glutathione transferase (GST) family, Sigma class GST, closely related to a leading Schistosome vaccine candidate (Sm28), has previously been revealed by proteomics in the liver fluke but not functionally characterised. METHODOLOGY/PRINCIPAL FINDINGS: In this manuscript we show that a purified recombinant form of the F. hepatica Sigma class GST possesses prostaglandin synthase activity and influences activity of host immune cells. Immunocytochemistry and western blotting have shown the protein is present near the surface of the fluke and expressed in eggs and newly excysted juveniles, and present in the excretory/secretory fraction of adults. We have assessed the potential to use F. hepatica Sigma class GST as a vaccine in a goat-based vaccine trial. No significant reduction of worm burden was found but we show significant reduction in the pathology normally associated with liver fluke infection. CONCLUSIONS/SIGNIFICANCE: We have shown that F. hepatica Sigma class GST has likely multi-functional roles in the host-parasite interaction from general detoxification and bile acid sequestration to PGD synthase activity.",2012 May 29,"['LaCourse, E. James', 'Perally, Samirah', 'Morphew, Russell M.', 'Moxon, Joseph V.', 'Prescott, Mark', 'Dowling, David J.', ""O'Neill, Sandra M."", 'Kipar, Anja', 'Hetzel, Udo', 'Hoey, Elizabeth', 'Zafra, Rafael', 'Buffoni, Leandro', 'Pérez Arévalo, José', 'Brophy, Peter M.']",PLoS Negl Trop Dis,,,True
72e9038e9738f001e0b050d11f9b05a6376919bc,PMC,Lessons from a one-year hospital-based surveillance of acute respiratory infections in Berlin- comparing case definitions to monitor influenza,http://dx.doi.org/10.1186/1471-2458-12-245,PMC3362781,22452874,CC BY,"BACKGROUND: Surveillance of severe acute respiratory infections (SARI) in sentinel hospitals is recommended to estimate the burden of severe influenza-cases. Therefore, we monitored patients admitted with respiratory infections (RI) in 9 Berlin hospitals from 7.12.2009 to 12.12.2010 according to different case definitions (CD) and determined the proportion of cases with influenza A(H1N1)pdm09 (pH1N1). We compared the sensitivity and specificity of CD for capturing pandemic pH1N1 cases. METHODS: We established an RI-surveillance restricted to adults aged ≤ 65 years within the framework of a pH1N1 vaccine effectiveness study, which required active identification of RI-cases. The hospital information-system was screened daily for newly admitted RI-patients. Nasopharyngeal swabs from consenting patients were tested by PCR for influenza-virus subtypes. Four clinical CD were compared in terms of capturing pH1N1-positives among hospitalized RI-patients by applying sensitivity and specificity analyses. The broadest case definition (CD1) was used for inclusion of RI-cases; the narrowest case definition (CD4) was identical to the SARI case definition recommended by ECDC/WHO. RESULTS: Over the study period, we identified 1,025 RI-cases, of which 283 (28%) met the ECDC/WHO SARI case definition. The percentage of SARI-cases among internal medicine admissions decreased from 3.2% (calendar-week 50-2009) to 0.2% (week 25-2010). Of 354 patients tested by PCR, 20 (6%) were pH1N1-positive. Two case definitions narrower than CD1 but -in contrast to SARI- not requiring shortness of breath yielded the largest areas under the Receiver-Operator-Curve. Heterogeneity of proportions of patients admitted with RI between hospitals was significant. CONCLUSIONS: Comprehensive surveillance of RI cases was feasible in a network of community hospitals. In most settings, several hospitals should be included to ensure representativeness. Although misclassification resulting from failure to obtain symptoms in the hospital information-system cannot be ruled out, a high proportion of hospitalized PCR-positive pH1N1-patients (45%) did not fulfil the SARI case-definition that included shortness of breath or difficulty breathing. Thus, to assess influenza-related disease burden in hospitals, broader, alternative case definitions should be considered.",2012 Mar 27,"['Nachtnebel, Matthias', 'Greutelaers, Benedikt', 'Falkenhorst, Gerhard', 'Jorgensen, Pernille', 'Dehnert, Manuel', 'Schweiger, Brunhilde', 'Träder, Christian', 'Buda, Silke', 'Eckmanns, Tim', 'Wichmann, Ole', 'Hellenbrand, Wiebke']",BMC Public Health,,,True
906902ba01987282a83ec42c2776de9c9bde3834,PMC,Discriminating Active from Latent Tuberculosis in Patients Presenting to Community Clinics,http://dx.doi.org/10.1371/journal.pone.0038080,PMC3364185,22666453,CC BY,"BACKGROUND: Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. METHODS: Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. RESULTS: 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%). CONCLUSIONS: We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings.",2012 May 30,"['Sandhu, Gurjinder', 'Battaglia, Francesca', 'Ely, Barry K.', 'Athanasakis, Dimitrios', 'Montoya, Rosario', 'Valencia, Teresa', 'Gilman, Robert H.', 'Evans, Carlton A.', 'Friedland, Jon S.', 'Fernandez-Reyes, Delmiro', 'Agranoff, Daniel D.']",PLoS One,,,True
6b47bb3bca780af716c9e986d983f1d2364136c4,PMC,Respiratory viruses in children hospitalized for acute lower respiratory tract infection in Ghana,http://dx.doi.org/10.1186/1743-422X-9-78,PMC3364910,22490115,CC BY,"BACKGROUND: Acute respiratory tract infections are one of the major causes of morbidity and mortality among young children in developing countries. Information on the viral aetiology of acute respiratory infections in developing countries is very limited. The study was done to identify viruses associated with acute lower respiratory tract infection among children less than 5 years. METHOD: Nasopharyngeal samples and blood cultures were collected from children less than 5 years who have been hospitalized for acute lower respiratory tract infection. Viruses and bacteria were identified using Reverse Transcriptase Real-Time Polymerase Chain Reaction and conventional biochemical techniques. RESULTS: Out of 128 patients recruited, 33(25.88%%, 95%CI: 18.5% to 34.2%) were positive for one or more viruses. Respiratory Syncytial Virus (RSV) was detected in 18(14.1%, 95%CI: 8.5% to 21.3%) patients followed by Adenoviruses (AdV) in 13(10.2%, 95%CI: 5.5% to 16.7%), Parainfluenza (PIV type: 1, 2, 3) in 4(3.1%, 95%CI: 0.9% to 7.8%) and influenza B viruses in 1(0.8%, 95%CI: 0.0 to 4.3). Concomitant viral and bacterial co-infection occurred in two patients. There were no detectable significant differences in the clinical signs, symptoms and severity for the various pathogens isolated. A total of 61.1% (22/36) of positive viruses were detected during the rainy season and Respiratory Syncytial Virus was the most predominant. CONCLUSION: The study has demonstrated an important burden of respiratory viruses as major causes of childhood acute respiratory infection in a tertiary health institution in Ghana. The data addresses a need for more studies on viral associated respiratory tract infection.",2012 Apr 10,"['Kwofie, Theophilus B', 'Anane, Yaw A', 'Nkrumah, Bernard', 'Annan, Augustina', 'Nguah, Samuel B', 'Owusu, Michael']",Virol J,,,True
86f450394e3530589eed829b5114c96d87513528,PMC,Longitudinal study on morbidity and mortality in white veal calves in Belgium,http://dx.doi.org/10.1186/1746-6148-8-26,PMC3366893,22414223,CC BY,"BACKGROUND: Mortality and morbidity are hardly documented in the white veal industry, despite high levels of antimicrobial drug use and resistance. The objective of the present study was to determine the causes and epidemiology of morbidity and mortality in dairy, beef and crossbred white veal production. A total of 5853 calves, housed in 15 production cohorts, were followed during one production cycle. Causes of mortality were determined by necropsy. Morbidity was daily recorded by the producers. RESULTS: The total mortality risk was 5,3% and was significantly higher in beef veal production compared to dairy or crossbreds. The main causes of mortality were pneumonia (1.3% of the calves at risk), ruminal disorders (0.7%), idiopathic peritonitis (0.5%), enterotoxaemia (0.5%) and enteritis (0.4%). Belgian Blue beef calves were more likely to die from pneumonia, enterotoxaemia and arthritis. Detection of bovine viral diarrhea virus at necropsy was associated with chronic pneumonia and pleuritis. Of the calves, 25.4% was treated individually and the morbidity rate was 1.66 cases per 1000 calf days at risk. The incidence rate of respiratory disease, diarrhea, arthritis and otitis was 0.95, 0.30, 0.11 and 0.07 cases per 1000 calf days at risk respectively. Morbidity peaked in the first three weeks after arrival and gradually declined towards the end of the production cycle. CONCLUSIONS: The present study provided insights into the causes and epidemiology of morbidity and mortality in white veal calves in Belgium, housed in the most frequent housing system in Europe. The necropsy findings, identified risk periods and differences between production systems can guide both veterinarians and producers towards the most profitable and ethical preventive and therapeutic protocols.",2012 Mar 14,"['Pardon, Bart', 'De Bleecker, Koen', 'Hostens, Miel', 'Callens, Jozefien', 'Dewulf, Jeroen', 'Deprez, Piet']",BMC Vet Res,,,True
a02d5fbeef1d5139b09a0e0017e7fe5e5c885e2c,PMC,Thermostable DNA Polymerase from a Viral Metagenome Is a Potent RT-PCR Enzyme,http://dx.doi.org/10.1371/journal.pone.0038371,PMC3366922,22675552,CC BY,"Viral metagenomic libraries are a promising but previously untapped source of new reagent enzymes. Deep sequencing and functional screening of viral metagenomic DNA from a near-boiling thermal pool identified clones expressing thermostable DNA polymerase (Pol) activity. Among these, 3173 Pol demonstrated both high thermostability and innate reverse transcriptase (RT) activity. We describe the biochemistry of 3173 Pol and report its use in single-enzyme reverse transcription PCR (RT-PCR). Wild-type 3173 Pol contains a proofreading 3′-5′ exonuclease domain that confers high fidelity in PCR. An easier-to-use exonuclease-deficient derivative was incorporated into a PyroScript RT-PCR master mix and compared to one-enzyme (Tth) and two-enzyme (MMLV RT/Taq) RT-PCR systems for quantitative detection of MS2 RNA, influenza A RNA, and mRNA targets. Specificity and sensitivity of 3173 Pol-based RT-PCR were higher than Tth Pol and comparable to three common two-enzyme systems. The performance and simplified set-up make this enzyme a potential alternative for research and molecular diagnostics.",2012 Jun 4,"['Moser, Michael J.', 'DiFrancesco, Robert A.', 'Gowda, Krishne', 'Klingele, Audrey J.', 'Sugar, Darby R.', 'Stocki, Stacy', 'Mead, David A.', 'Schoenfeld, Thomas W.']",PLoS One,,,True
8894267c458259ec6e58acbfad98a82c84519711,PMC,Novel Evidence of HBV Recombination in Family Cluster Infections in Western China,http://dx.doi.org/10.1371/journal.pone.0038241,PMC3366946,22675528,CC BY,"Two hepatitis B virus (HBV) C/D recombinants were isolated from western China. No direct evidence indicates that these new viruses arose as a result of recombination between genotype C and D or a result of convergence. In this study, we search for evidence of intra-individual recombination in the family cluster cases with co-circulation of genotype C, D and C/D recombinants. We studied 68 individuals from 15 families with HBV infections in 2006, identified individuals with mixed HBV genotype co-infections by restriction fragment length polymorphism and proceeded with cloning and DNA sequencing. Recombination signals were detected by RDP3 software and confirmed by split phylogenetic trees. Families with mixed HBV genotype co-infections were resampled in 2007. Three of 15 families had individuals with different HBV genotype co-infections in 2006. One individual (Y2) had a triple infection of HBV genotype C, D and C/D recombinant in 2006, but only genotype D in 2007. Further clonal analysis of this patient indicated that the C/D recombinant was not identical to previously isolated CD1 or CD2, but many novel recombinants with C2, D1 and CD1 were simultaneously found. All parental strains could recombine with each other to form new recombinant in this patient. This indicates that the detectable mixed infection and recombination have a limited time window. Also, as the recombinant nature of HBV precludes the possibility of a simple phylogenetic taxonomy, a new standard may be required for classifying HBV sequences.",2012 Jun 4,"['Zhou, Bin', 'Wang, Zhanhui', 'Yang, Jie', 'Sun, Jian', 'Li, Hua', 'Tanaka, Yasuhito', 'Mizokami, Masashi', 'Hou, Jinlin']",PLoS One,,,True
e81fa612268526f1a649e7d5e70c90dc9c1c4cca,PMC,Identifying Live Bird Markets with the Potential to Act as Reservoirs of Avian Influenza A (H5N1) Virus: A Survey in Northern Viet Nam and Cambodia,http://dx.doi.org/10.1371/journal.pone.0037986,PMC3366999,22675502,CC BY,"Wet markets are common in many parts of the world and may promote the emergence, spread and maintenance of livestock pathogens, including zoonoses. A survey was conducted in order to assess the potential of Vietnamese and Cambodian live bird markets (LBMs) to sustain circulation of highly pathogenic avian influenza virus subtype H5N1 (HPAIV H5N1). Thirty Vietnamese and 8 Cambodian LBMs were visited, and structured interviews were conducted with the market managers and 561 Vietnamese and 84 Cambodian traders. Multivariate and cluster analysis were used to construct a typology of traders based on their poultry management practices. As a result of those practices and large poultry surplus (unsold poultry reoffered for sale the following day), some poultry traders were shown to promote conditions favorable for perpetuating HPAIV H5N1 in LBMs. More than 80% of these traders operated in LBMs located in the most densely populated areas, Ha Noi and Phnom Penh. The profiles of sellers operating at a given LBM could be reliably predicted using basic information about the location and type of market. Consequently, LBMs with the largest combination of risk factors for becoming virus reservoirs could be easily identified, potentially allowing control strategies to be appropriately targeted. These findings are of particular relevance to resource-scarce settings with extensively developed LBM systems, commonly found in South-East Asia.",2012 Jun 4,"['Fournié, Guillaume', 'Guitian, Javier', 'Desvaux, Stéphanie', 'Mangtani, Punam', 'Ly, Sowath', 'Cong, Vu Chi', 'San, Sorn', 'Dung, Do Huu', 'Holl, Davun', 'Pfeiffer, Dirk U.', 'Vong, Sirenda', 'Ghani, Azra C.']",PLoS One,,,True
7d3b1ce33b6c181f3509a9cfa9d6aab1e53c2eaa,PMC,Clinical Relevance and Discriminatory Value of Elevated Liver Aminotransferase Levels for Dengue Severity,http://dx.doi.org/10.1371/journal.pntd.0001676,PMC3367991,22679523,CC BY,"BACKGROUND: Elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is prominent in acute dengue illness. The World Health Organization (WHO) 2009 dengue guidelines defined AST or ALT≥1000 units/liter (U/L) as a criterion for severe dengue. We aimed to assess the clinical relevance and discriminatory value of AST or ALT for dengue hemorrhagic fever (DHF) and severe dengue. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively studied and classified polymerase chain reaction positive dengue patients from 2006 to 2008 treated at Tan Tock Seng Hospital, Singapore according to WHO 1997 and 2009 criteria for dengue severity. Of 690 dengue patients, 31% had DHF and 24% severe dengue. Elevated AST and ALT occurred in 86% and 46%, respectively. Seven had AST or ALT≥1000 U/L. None had acute liver failure but one patient died. Median AST and ALT values were significantly higher with increasing dengue severity by both WHO 1997 and 2009 criteria. However, they were poorly discriminatory between non-severe and severe dengue (e.g., AST area under the receiver operating characteristic [ROC] curve = 0.62; 95% confidence interval [CI]: 0.57–0.67) and between dengue fever (DF) and DHF (AST area under the ROC curve = 0.56; 95% CI: 0.52–0.61). There was significant overlap in AST and ALT values among patients with dengue with or without warning signs and severe dengue, and between those with DF and DHF. CONCLUSIONS: Although aminotransferase levels increased in conjunction with dengue severity, AST or ALT values did not discriminate between DF and DHF or non-severe and severe dengue.",2012 Jun 5,"['Lee, Linda K.', 'Gan, Victor C.', 'Lee, Vernon J.', 'Tan, Adriana S.', 'Leo, Yee Sin', 'Lye, David C.']",PLoS Negl Trop Dis,,,True
a234c5ac982ffc63b7be9d7c1b3473f92849192e,PMC,Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection,http://dx.doi.org/10.1371/journal.pone.0038214,PMC3367995,22679491,CC BY,"Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.",2012 Jun 5,"['Paquette, Stéphane G.', 'Banner, David', 'Zhao, Zhen', 'Fang, Yuan', 'Huang, Stephen S. H.', 'Leόn, Alberto J.', 'Ng, Derek C. K.', 'Almansa, Raquel', 'Martin-Loeches, Ignacio', 'Ramirez, Paula', 'Socias, Lorenzo', 'Loza, Ana', 'Blanco, Jesus', 'Sansonetti, Paola', 'Rello, Jordi', 'Andaluz, David', 'Shum, Bianche', 'Rubino, Salvatore', 'de Lejarazu, Raul Ortiz', 'Tran, Dat', 'Delogu, Giovanni', 'Fadda, Giovanni', 'Krajden, Sigmund', 'Rubin, Barry B.', 'Bermejo-Martin, Jesús F.', 'Kelvin, Alyson A.', 'Kelvin, David J.']",PLoS One,,,True
d25e47796b1250f545c2b7e5b2dc191eaa3735f0,PMC,Microarray-based method for screening of immunogenic proteins from bacteria,http://dx.doi.org/10.1186/1477-3155-10-12,PMC3368735,22436172,CC BY,"BACKGROUND: Detection of immunogenic proteins remains an important task for life sciences as it nourishes the understanding of pathogenicity, illuminates new potential vaccine candidates and broadens the spectrum of biomarkers applicable in diagnostic tools. Traditionally, immunoscreenings of expression libraries via polyclonal sera on nitrocellulose membranes or screenings of whole proteome lysates in 2-D gel electrophoresis are performed. However, these methods feature some rather inconvenient disadvantages. Screening of expression libraries to expose novel antigens from bacteria often lead to an abundance of false positive signals owing to the high cross reactivity of polyclonal antibodies towards the proteins of the expression host. A method is presented that overcomes many disadvantages of the old procedures. RESULTS: Four proteins that have previously been described as immunogenic have successfully been assessed immunogenic abilities with our method. One protein with no known immunogenic behaviour before suggested potential immunogenicity. We incorporated a fusion tag prior to our genes of interest and attached the expressed fusion proteins covalently on microarrays. This enhances the specific binding of the proteins compared to nitrocellulose. Thus, it helps to reduce the number of false positives significantly. It enables us to screen for immunogenic proteins in a shorter time, with more samples and statistical reliability. We validated our method by employing several known genes from Campylobacter jejuni NCTC 11168. CONCLUSIONS: The method presented offers a new approach for screening of bacterial expression libraries to illuminate novel proteins with immunogenic features. It could provide a powerful and attractive alternative to existing methods and help to detect and identify vaccine candidates, biomarkers and potential virulence-associated factors with immunogenic behaviour furthering the knowledge of virulence and pathogenicity of studied bacteria.",2012 Mar 21,"['Hoppe, Sebastian', 'Bier, Frank F', 'von Nickisch-Rosenegk, Markus']",J Nanobiotechnology,,,True
6694490cc1353addf66465e4d06419ff0b0af753,PMC,Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain,http://dx.doi.org/10.1186/1742-2094-9-50,PMC3368782,22405261,CC BY,"BACKGROUND: Neuropathology caused by acute viral infection of the brain is associated with the development of persistent neurological deficits. Identification of the immune effectors responsible for injuring the brain during acute infection is necessary for the development of therapeutic strategies that reduce neuropathology but maintain immune control of the virus. METHODS: The identity of brain-infiltrating leukocytes was determined using microscopy and flow cytometry at several acute time points following intracranial infection of mice with the Theiler's murine encephalomyelitis virus. Behavioral consequences of immune cell depletion were assessed by Morris water maze. RESULTS: Inflammatory monocytes, defined as CD45(hi)CD11b(++)F4/80(+)Gr1(+)1A8(-), and neutrophils, defined as CD45(hi)CD11b(+++)F4/80(-)Gr1(+)1A8(+), were found in the brain at 12 h after infection. Flow cytometry of brain-infiltrating leukocytes collected from LysM: GFP reporter mice confirmed the identification of neutrophils and inflammatory monocytes in the brain. Microscopy of sections from infected LysM:GFP mice showed that infiltrating cells were concentrated in the hippocampal formation. Immunostaining confirmed that neutrophils and inflammatory monocytes were localized to the hippocampal formation at 12 h after infection. Immunodepletion of inflammatory monocytes and neutrophils but not of neutrophils only resulted in preservation of hippocampal neurons. Immunodepletion of inflammatory monocytes also preserved cognitive function as assessed by the Morris water maze. CONCLUSIONS: Neutrophils and inflammatory monocytes rapidly and robustly responded to Theiler's virus infection by infiltrating the brain. Inflammatory monocytes preceded neutrophils, but both cell types were present in the hippocampal formation at a timepoint that is consistent with a role in triggering hippocampal pathology. Depletion of inflammatory monocytes and neutrophils with the Gr1 antibody resulted in hippocampal neuroprotection and preservation of cognitive function. Specific depletion of neutrophils with the 1A8 antibody failed to preserve neurons, suggesting that inflammatory monocytes are the key effectors of brain injury during acute picornavirus infection of the brain. These effector cells may be important therapeutic targets for immunomodulatory or immunosuppressive therapies aimed at reducing or preventing central nervous system pathology associated with acute viral infection.",2012 Mar 9,"['Howe, Charles L', 'LaFrance-Corey, Reghann G', 'Sundsbak, Rhianna S', 'LaFrance, Stephanie J']",J Neuroinflammation,,,True
ec7e7937ff0f3f8561b73eb8a4d34de49e35e3ff,PMC,HHV-6B Induces IFN-Lambda1 Responses in Cord Plasmacytoid Dendritic Cells through TLR9,http://dx.doi.org/10.1371/journal.pone.0038683,PMC3368904,22701693,CC BY,"Human herpesvirus type 6B (HHV-6B) is a strong inducer of IFN-alpha and has the capacity to promote Th1 responses and block Th2 responses in vitro. In this study we addressed whether inactivated HHV-6B can also induce IFN lambda responses and to what extent interferons alpha and lambda affect Th1/Th2 polarization. We show that inactivated HHV-6B induced IFN-lambda1 (IL-29) but not IFN-lambda2 (IL-28A) responses in plasmacytoid DC and that this induction was mediated through TLR9. We have previously shown that HHV-6B promotes Th1 responses and blocks Th2 responses in both humans and mice. We now show that neutralization of IFN-alpha but not IFN-lambda1 blocked the HHV-6B-induced enhancement of Th1 responses in MLR, but did not affect the HHV-6-induced dampening of Th2 responses. Similarly, blockage of TLR9 counteracted HHV-6Bs effects on the Th1/Th2 balance. In addition, IFN-alpha but not IFN-lambda1 promoted IFN-gamma production and blocked IL-5 and IL-13 production in purified CD4+ T-cells. The lack of effect of IFN-lambda1 correlated with the absence of the IFN-lambda receptor IL-28Ralfa chain on the cell surface of both resting and activated CD4+ T-cells. We conclude that inactivated HHV-6B is a strong inducer of IFN-lambda1 in plasmacytoid DC and that this induction is TLR9-dependent. However, human CD4+ T-cells do not express the IFN-lambda receptor and are refractory to IFN-lambda1 treatment. The HHV-6B-induced alterations in the Th1/Th2 balance are instead mediated mainly through TLR9 and IFN-alpha.",2012 Jun 6,"['Nordström, Inger', 'Eriksson, Kristina']",PLoS One,,,True
349137610648c4aa4a6770afc625a3ea369fb0e3,PMC,Directed Fusion of Mesenchymal Stem Cells with Cardiomyocytes via VSV-G Facilitates Stem Cell Programming,http://dx.doi.org/10.1155/2012/414038,PMC3369562,22701126,CC BY,"Mesenchymal stem cells (MSCs) spontaneously fuse with somatic cells in vivo, albeit rarely, and the fusion products are capable of tissue-specific function (mature trait) or proliferation (immature trait), depending on the microenvironment. That stem cells can be programmed, or somatic cells reprogrammed, in this fashion suggests that stem cell fusion holds promise as a therapeutic approach for the repair of damaged tissues, especially tissues not readily capable of functional regeneration, such as the myocardium. In an attempt to increase the frequency of stem cell fusion and, in so doing, increase the potential for cardiac tissue repair, we expressed the fusogen of the vesicular stomatitis virus (VSV-G) in human MSCs. We found VSV-G expressing MSCs (vMSCs) fused with cardiomyocytes (CMs) and these fusion products adopted a CM-like phenotype and morphology in vitro. In vivo, vMSCs delivered to damaged mouse myocardium via a collagen patch were able to home to the myocardium and fuse to cells within the infarct and peri-infarct region of the myocardium. This study provides a basis for the investigation of the biological impact of fusion of stem cells with CMs in vivo and illustrates how viral fusion proteins might better enable such studies.",2012 May 30,"['Kouris, Nicholas A.', 'Schaefer, Jeremy A.', 'Hatta, Masato', 'Freeman, Brian T.', 'Kamp, Timothy J.', 'Kawaoka, Yoshihiro', 'Ogle, Brenda M.']",Stem Cells Int,,,False
20651c857a793c827bc2d32bbbf6392e8285b84d,PMC,Directed Fusion of Mesenchymal Stem Cells with Cardiomyocytes via VSV-G Facilitates Stem Cell Programming,http://dx.doi.org/10.1155/2012/414038,PMC3369562,22701126,CC BY,"Mesenchymal stem cells (MSCs) spontaneously fuse with somatic cells in vivo, albeit rarely, and the fusion products are capable of tissue-specific function (mature trait) or proliferation (immature trait), depending on the microenvironment. That stem cells can be programmed, or somatic cells reprogrammed, in this fashion suggests that stem cell fusion holds promise as a therapeutic approach for the repair of damaged tissues, especially tissues not readily capable of functional regeneration, such as the myocardium. In an attempt to increase the frequency of stem cell fusion and, in so doing, increase the potential for cardiac tissue repair, we expressed the fusogen of the vesicular stomatitis virus (VSV-G) in human MSCs. We found VSV-G expressing MSCs (vMSCs) fused with cardiomyocytes (CMs) and these fusion products adopted a CM-like phenotype and morphology in vitro. In vivo, vMSCs delivered to damaged mouse myocardium via a collagen patch were able to home to the myocardium and fuse to cells within the infarct and peri-infarct region of the myocardium. This study provides a basis for the investigation of the biological impact of fusion of stem cells with CMs in vivo and illustrates how viral fusion proteins might better enable such studies.",2012 May 30,"['Kouris, Nicholas A.', 'Schaefer, Jeremy A.', 'Hatta, Masato', 'Freeman, Brian T.', 'Kamp, Timothy J.', 'Kawaoka, Yoshihiro', 'Ogle, Brenda M.']",Stem Cells Int,,,True
83447780f68227bd566b75739a926149c96ff3d1,PMC,Design Novel Dual Agonists for Treating Type-2 Diabetes by Targeting Peroxisome Proliferator-Activated Receptors with Core Hopping Approach,http://dx.doi.org/10.1371/journal.pone.0038546,PMC3369836,22685582,CC BY,"Owing to their unique functions in regulating glucose, lipid and cholesterol metabolism, PPARs (peroxisome proliferator-activated receptors) have drawn special attention for developing drugs to treat type-2 diabetes. By combining the lipid benefit of PPAR-alpha agonists (such as fibrates) with the glycemic advantages of the PPAR-gamma agonists (such as thiazolidinediones), the dual PPAR agonists approach can both improve the metabolic effects and minimize the side effects caused by either agent alone, and hence has become a promising strategy for designing effective drugs against type-2 diabetes. In this study, by means of the powerful “core hopping” and “glide docking” techniques, a novel class of PPAR dual agonists was discovered based on the compound GW409544, a well-known dual agonist for both PPAR-alpha and PPAR-gamma modified from the farglitazar structure. It was observed by molecular dynamics simulations that these novel agonists not only possessed the same function as GW409544 did in activating PPAR-alpha and PPAR-gamma, but also had more favorable conformation for binding to the two receptors. It was further validated by the outcomes of their ADME (absorption, distribution, metabolism, and excretion) predictions that the new agonists hold high potential to become drug candidates. Or at the very least, the findings reported here may stimulate new strategy or provide useful insights for discovering more effective dual agonists for treating type-2 diabetes. Since the “core hopping” technique allows for rapidly screening novel cores to help overcome unwanted properties by generating new lead compounds with improved core properties, it has not escaped our notice that the current strategy along with the corresponding computational procedures can also be utilized to find novel and more effective drugs for treating other illnesses.",2012 Jun 7,"['Ma, Ying', 'Wang, Shu-Qing', 'Xu, Wei-Ren', 'Wang, Run-Ling', 'Chou, Kuo-Chen']",PLoS One,,,True
f7204b21080d07e2bb6ffc6fedaa1bf60ba5d67c,PMC,Application of Consensus Scoring and Principal Component Analysis for Virtual Screening against β-Secretase (BACE-1),http://dx.doi.org/10.1371/journal.pone.0038086,PMC3372491,22701601,CC BY,"BACKGROUND: In order to identify novel chemical classes of β-secretase (BACE-1) inhibitors, an alternative scoring protocol, Principal Component Analysis (PCA), was proposed to summarize most of the information from the original scoring functions and re-rank the results from the virtual screening against BACE-1. METHOD: Given a training set (50 BACE-1 inhibitors and 9950 inactive diverse compounds), three rank-based virtual screening methods, individual scoring, conventional consensus scoring and PCA, were judged by the hit number in the top 1% of the ranked list. The docking poses were generated by Surflex, five scoring functions (Surflex_Score, D_Score, G_Score, ChemScore, and PMF_Score) were used for pose extraction. For each pose group, twelve scoring functions (Surflex_Score, D_Score, G_Score, ChemScore, PMF_Score, LigScore1, LigScore2, PLP1, PLP2, jain, Ludi_1, and Ludi_2) were used for the pose rank. For a test set, 113,228 chemical compounds (Sigma-Aldrich® corporate chemical directory) were docked by Surflex, then ranked by the same three ranking methods motioned above to select the potential active compounds for experimental test. RESULTS: For the training set, the PCA approach yielded consistently superior rankings compared to conventional consensus scoring and single scoring. For the test set, the top 20 compounds according to conventional consensus scoring were experimentally tested, no inhibitor was found. Then, we relied on PCA scoring protocol to test another different top 20 compounds and two low micromolar inhibitors (S450588 and 276065) were emerged through the BACE-1 fluorescence resonance energy transfer (FRET) assay. CONCLUSION: The PCA method extends the conventional consensus scoring in a quantitative statistical manner and would appear to have considerable potential for chemical screening applications.",2012 Jun 11,"['Liu, Shu', 'Fu, Rao', 'Zhou, Li-Hua', 'Chen, Sheng-Ping']",PLoS One,,,True
0d0a0fdfcb384b60703d3ea329672f668d7c118e,PMC,Investigation of the Plasmodium falciparum Food Vacuole through Inducible Expression of the Chloroquine Resistance Transporter (PfCRT),http://dx.doi.org/10.1371/journal.pone.0038781,PMC3374814,22719945,CC BY,"Haemoglobin degradation during the erythrocytic life stages is the major function of the food vacuole (FV) of Plasmodium falciparum and the target of several anti-malarial drugs that interfere with this metabolic pathway, killing the parasite. Two multi-spanning food vacuole membrane proteins are known, the multidrug resistance protein 1 (PfMDR1) and Chloroquine Resistance Transporter (PfCRT). Both modulate resistance to drugs that act in the food vacuole. To investigate the formation and behaviour of the food vacuole membrane we have generated inducible GFP fusions of chloroquine sensitive and resistant forms of the PfCRT protein. The inducible expression system allowed us to follow newly-induced fusion proteins, and corroborated a previous report of a direct trafficking route from the ER/Golgi to the food vacuole membrane. These parasites also allowed the definition of a food vacuole compartment in ring stage parasites well before haemozoin crystals were apparent, as well as the elucidation of secondary PfCRT-labelled compartments adjacent to the food vacuole in late stage parasites. We demonstrated that in addition to previously demonstrated Brefeldin A sensitivity, the trafficking of PfCRT is disrupted by Dynasore, a non competitive inhibitor of dynamin-mediated vesicle formation. Chloroquine sensitivity was not altered in parasites over-expressing chloroquine resistant or sensitive forms of the PfCRT fused to GFP, suggesting that the PfCRT does not mediate chloroquine transport as a GFP fusion protein.",2012 Jun 13,"['Ehlgen, Florian', 'Pham, James S.', 'de Koning-Ward, Tania', 'Cowman, Alan F.', 'Ralph, Stuart A.']",PLoS One,,,True
f2a43da3e565ffb44289385ed3c6a4658dc166c1,PMC,"The Acute Environment, Rather than T Cell Subset Pre-Commitment, Regulates Expression of the Human T Cell Cytokine Amphiregulin",http://dx.doi.org/10.1371/journal.pone.0039072,PMC3375254,22720031,CC BY,"Cytokine expression patterns of T cells can be regulated by pre-commitment to stable effector phenotypes, further modification of moderately stable phenotypes, and quantitative changes in cytokine production in response to acute signals. We showed previously that the epidermal growth factor family member Amphiregulin is expressed by T cell receptor-activated mouse CD4 T cells, particularly Th2 cells, and helps eliminate helminth infection. Here we report a detailed analysis of the regulation of Amphiregulin expression by human T cell subsets. Signaling through the T cell receptor induced Amphiregulin expression by most or all T cell subsets in human peripheral blood, including naive and memory CD4 and CD8 T cells, Th1 and Th2 in vitro T cell lines, and subsets of memory CD4 T cells expressing several different chemokine receptors and cytokines. In these different T cell types, Amphiregulin synthesis was inhibited by an antagonist of protein kinase A, a downstream component of the cAMP signaling pathway, and enhanced by ligands that increased cAMP or directly activated protein kinase A. Prostaglandin E2 and adenosine, natural ligands that stimulate adenylyl cyclase activity, also enhanced Amphiregulin synthesis while reducing synthesis of most other cytokines. Thus, in contrast to mouse T cells, Amphiregulin synthesis by human T cells is regulated more by acute signals than pre-commitment of T cells to a particular cytokine pattern. This may be appropriate for a cytokine more involved in repair than attack functions during most inflammatory responses.",2012 Jun 14,"['Qi, Yilin', 'Operario, Darwin J.', 'Georas, Steve N.', 'Mosmann, Tim R.']",PLoS One,,,True
6d12d0dd222c803e8a4e4f3e516d5feecd103358,PMC,Two Glycosylation Sites in H5N1 Influenza Virus Hemagglutinin That Affect Binding Preference by Computer-Based Analysis,http://dx.doi.org/10.1371/journal.pone.0038794,PMC3375263,22719948,CC BY,"Increasing numbers of H5N1 influenza viruses (IVs) are responsible for human deaths, especially in North Africa and Southeast Asian. The binding of hemagglutinin (HA) on the viral surface to host sialic acid (SA) receptors is a requisite step in the infection process. Phylogenetic analysis reveals that H5N1 viruses can be divided into 10 clades based on their HA sequences, with most human IVs centered from clade 1 and clade 2.1 to clade 2.3. Protein sequence alignment in various clades indicates the high conservation in the receptor-binding domains (RBDs) is essential for binding with the SA receptor. Two glycosylation sites, 158N and 169N, also participate in receptor recognition. In the present work, we attempted to construct a serial H5N1 HA models including diverse glycosylated HAs to simulate the binding process with various SA receptors in silico. As the SA-α-2,3-Gal and SA-α-2,6-Gal receptor adopted two distinctive topologies, straight and fishhook-like, respectively, the presence of N-glycans at 158N would decrease the affinity of HA for all of the receptors, particularly SA-α-2,6-Gal analogs. The steric clashes of the huge glycans shown at another glycosylation site, 169N, located on an adjacent HA monomer, would be more effective in preventing the binding of SA-α-2,3-Gal analogs.",2012 Jun 14,"['Chen, Wentian', 'Sun, Shisheng', 'Li, Zheng']",PLoS One,,,True
6d1a2055895ffdcdf57aabcaf436f176b1650c50,PMC,Characterization of Human Coronavirus Etiology in Chinese Adults with Acute Upper Respiratory Tract Infection by Real-Time RT-PCR Assays,http://dx.doi.org/10.1371/journal.pone.0038638,PMC3376151,22719912,CC BY,"BACKGROUND: In addition to SARS associated coronaviruses, 4 non-SARS related human coronaviruses (HCoVs) are recognized as common respiratory pathogens. The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI) needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. All specimens were also tested for the presence of other common respiratory viruses and newly identified viruses, human metapneumovirus (hMPV) and human bocavirus (HBoV). 157 of the 981 (16.0%) nasopharyngeal swabs were positive for HCoVs. The species detected were 229E (96 cases, 9.8%), OC43 (42 cases, 4.3%), HKU1 (16 cases, 1.6%) and NL63 (11 cases, 1.1%). HCoV-229E was circulated in 21 of the 24 months of surveillance. The detection rates for both OC43 and NL63 were showed significantly year-to-year variation between 2009/10 and 2010/11, respectively (P<0.001 and P = 0.003), and there was a higher detection frequency of HKU1 in patients aged over 60 years (P = 0.03). 48 of 157(30.57%) HCoV positive patients were co-infected. Undifferentiated human rhinoviruses and influenza (Flu) A were the most common viruses detected (more than 35%) in HCoV co-infections. Respiratory syncytial virus (RSV), human parainfluenza virus (PIV) and HBoV were detected in very low rate (less than 1%) among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. Our study also suggested that all non-SARS-associated HCoVs contribute significantly to URTI in adult patients in China.",2012 Jun 15,"['Lu, Roujian', 'Yu, Xiaoyan', 'Wang, Wen', 'Duan, Xijie', 'Zhang, Linglin', 'Zhou, Weimin', 'Xu, Jin', 'Xu, Lingjie', 'Hu, Qin', 'Lu, Jianxin', 'Ruan, Li', 'Wang, Zhong', 'Tan, Wenjie']",PLoS One,,,True
acb470a7f8d734e4f257454a90cbb1d933d8bebf,PMC,UNC93B1 Mediates Innate Inflammation and Antiviral Defense in the Liver during Acute Murine Cytomegalovirus Infection,http://dx.doi.org/10.1371/journal.pone.0039161,PMC3377622,22723955,CC BY,"Antiviral defense in the liver during acute infection with the hepatotropic virus murine cytomegalovirus (MCMV) involves complex cytokine and cellular interactions. However, the mechanism of viral sensing in the liver that promotes these cytokine and cellular responses has remained unclear. Studies here were undertaken to investigate the role of nucleic acid-sensing Toll-like receptors (TLRs) in initiating antiviral immunity in the liver during infection with MCMV. We examined the host response of UNC93B1 mutant mice, which do not signal properly through TLR3, TLR7 and TLR9, to acute MCMV infection to determine whether liver antiviral defense depends on signaling through these molecules. Infection of UNC93B1 mutant mice revealed reduced production of systemic and liver proinflammatory cytokines including IFN-α, IFN-γ, IL-12 and TNF-α when compared to wild-type. UNC93B1 deficiency also contributed to a transient hepatitis later in acute infection, evidenced by augmented liver pathology and elevated systemic alanine aminotransferase levels. Moreover, viral clearance was impaired in UNC93B1 mutant mice, despite intact virus-specific CD8+ T cell responses in the liver. Altogether, these results suggest a combined role for nucleic acid-sensing TLRs in promoting early liver antiviral defense during MCMV infection.",2012 Jun 18,"['Crane, Meredith J.', 'Gaddi, Pamela J.', 'Salazar-Mather, Thais P.']",PLoS One,,,True
eff26d8739498efca2d32fe2e66cdbebf0569c50,PMC,Bioinformatics analysis of rabbit haemorrhagic disease virus genome,http://dx.doi.org/10.1186/1743-422X-8-494,PMC3377956,22044910,CC BY,"BACKGROUND: Rabbit haemorrhagic disease virus (RHDV), as the pathogeny of Rabbit haemorrhagic disease, can cause a highly infectious and often fatal disease only affecting wild and domestic rabbits. Recent researches revealed that it, as one number of the Caliciviridae, has some specialties in its genome, its reproduction and so on. RESULTS: In this report, we firstly analyzed its genome and two open reading frameworks (ORFs) from this aspect of codon usage bias. Our researches indicated that mutation pressure rather than natural is the most important determinant in RHDV with high codon bias, and the codon usage bias is nearly contrary between ORF1 and ORF2, which is maybe one of factors regulating the expression of VP60 (encoding by ORF1) and VP10 (encoding by ORF2). Furthermore, negative selective constraints on the RHDV whole genome implied that VP10 played an important role in RHDV lifecycle. CONCLUSIONS: We conjectured that VP10 might be beneficial for the replication, release or both of virus by inducing infected cell apoptosis initiate by RHDV. According to the results of the principal component analysis for ORF2 of RSCU, we firstly separated 30 RHDV into two genotypes, and the ENC values indicated ORF1 and ORF2 were independent among the evolution of RHDV.",2011 Nov 1,"['Tian, Xiao-ting', 'Li, Bao-yu', 'Zhang, Liang', 'Jiao, Wen-qiang', 'Liu, Ji-xing']",Virol J,,,True
123683340d6d91bf7251d4b91b7503f907dd56cc,PMC,Oligonucleotide Based Magnetic Bead Capture of Onchocerca volvulus DNA for PCR Pool Screening of Vector Black Flies,http://dx.doi.org/10.1371/journal.pntd.0001712,PMC3378604,22724041,CC BY,"BACKGROUND: Entomological surveys of Simulium vectors are an important component in the criteria used to determine if Onchocerca volvulus transmission has been interrupted and if focal elimination of the parasite has been achieved. However, because infection in the vector population is quite rare in areas where control has succeeded, large numbers of flies need to be examined to certify transmission interruption. Currently, this is accomplished through PCR pool screening of large numbers of flies. The efficiency of this process is limited by the size of the pools that may be screened, which is in turn determined by the constraints imposed by the biochemistry of the assay. The current method of DNA purification from pools of vector black flies relies upon silica adsorption. This method can be applied to screen pools containing a maximum of 50 individuals (from the Latin American vectors) or 100 individuals (from the African vectors). METHODOLOGY/PRINCIPAL FINDINGS: We have evaluated an alternative method of DNA purification for pool screening of black flies which relies upon oligonucleotide capture of Onchocerca volvulus genomic DNA from homogenates prepared from pools of Latin American and African vectors. The oligonucleotide capture assay was shown to reliably detect one O. volvulus infective larva in pools containing 200 African or Latin American flies, representing a two-four fold improvement over the conventional assay. The capture assay requires an equivalent amount of technical time to conduct as the conventional assay, resulting in a two-four fold reduction in labor costs per insect assayed and reduces reagent costs to $3.81 per pool of 200 flies, or less than $0.02 per insect assayed. CONCLUSIONS/SIGNIFICANCE: The oligonucleotide capture assay represents a substantial improvement in the procedure used to detect parasite prevalence in the vector population, a major metric employed in the process of certifying the elimination of onchocerciasis.",2012 Jun 19,"['Gopal, Hemavathi', 'Hassan, Hassan K.', 'Rodríguez-Pérez, Mario A.', 'Toé, Laurent D.', 'Lustigman, Sara', 'Unnasch, Thomas R.']",PLoS Negl Trop Dis,,,True
68011fab7fc7a4d29797a161cb32d21ffd2a2ea7,PMC,Prediction and Identification of T Cell Epitopes in the H5N1 Influenza Virus Nucleoprotein in Chicken,http://dx.doi.org/10.1371/journal.pone.0039344,PMC3379973,22745738,CC BY,"T cell epitopes can be used for the accurate monitoring of avian influenza virus (AIV) immune responses and the rational design of vaccines. No T cell epitopes have been previously identified in the H5N1 AIV virus nucleoprotein (NP) in chickens. For the first time, this study used homology modelling techniques to construct three-dimensional structures of the peptide-binding domains of chicken MHC class Ι molecules for four commonly encountered unique haplotypes, i.e., B4, B12, B15, and B19. H5N1 AIV NP was computationally parsed into octapeptides or nonapeptides according to the peptide-binding motifs of MHC class I molecules of the B4, B12, B15 and B19 haplotypes. Seventy-five peptide sequences were modelled and their MHC class I molecule-binding abilities were analysed by molecular docking. Twenty-five peptides (Ten for B4, six for B12, two for B15, and seven for B19) were predicted to be potential T cell epitopes in chicken. Nine of these peptides and one unrelated peptide were manually synthesized and their T cell responses were tested in vitro. Spleen lymphocytes were collected from SPF chickens that had been immunised with a NP-expression plasmid, pCAGGS-NP, and they were stimulated using the synthesized peptides. The secretion of chicken IFN-γ and the proliferation of CD8(+) T cells were tested using an ELISA kit and flow cytometry, respectively. The significant secretion of chicken IFN-γ and proliferation of CD8(+) T lymphocytes increased by 13.7% and 11.9% were monitored in cells stimulated with peptides NP(89–97) and NP(198–206), respectively. The results indicate that peptides NP(89–97) (PKKTGGPIY) and NP(198–206) (KRGINDRNF) are NP T cell epitopes in chicken of certain haplotypes. The method used in this investigation is applicable to predicting T cell epitopes for other antigens in chicken, while this study also extends our understanding of the mechanisms of the immune response to AIV in chicken.",2012 Jun 20,"['Hou, Yanxia', 'Guo, Yingying', 'Wu, Chunyan', 'Shen, Nan', 'Jiang, Yongping', 'Wang, Jingfei']",PLoS One,,,True
4241f93b9e7128d98e8b1e81a410999283bc3599,PMC,Model Selection in Time Series Studies of Influenza-Associated Mortality,http://dx.doi.org/10.1371/journal.pone.0039423,PMC3380027,22745751,CC BY,"BACKGROUND: Poisson regression modeling has been widely used to estimate influenza-associated disease burden, as it has the advantage of adjusting for multiple seasonal confounders. However, few studies have discussed how to judge the adequacy of confounding adjustment. This study aims to compare the performance of commonly adopted model selection criteria in terms of providing a reliable and valid estimate for the health impact of influenza. METHODS: We assessed four model selection criteria: quasi Akaike information criterion (QAIC), quasi Bayesian information criterion (QBIC), partial autocorrelation functions of residuals (PACF), and generalized cross-validation (GCV), by separately applying them to select the Poisson model best fitted to the mortality datasets that were simulated under the different assumptions of seasonal confounding. The performance of these criteria was evaluated by the bias and root-mean-square error (RMSE) of estimates from the pre-determined coefficients of influenza proxy variable. These four criteria were subsequently applied to an empirical hospitalization dataset to confirm the findings of simulation study. RESULTS: GCV consistently provided smaller biases and RMSEs for the influenza coefficient estimates than QAIC, QBIC and PACF, under the different simulation scenarios. Sensitivity analysis of different pre-determined influenza coefficients, study periods and lag weeks showed that GCV consistently outperformed the other criteria. Similar results were found in applying these selection criteria to estimate influenza-associated hospitalization. CONCLUSIONS: GCV criterion is recommended for selection of Poisson models to estimate influenza-associated mortality and morbidity burden with proper adjustment for confounding. These findings shall help standardize the Poisson modeling approach for influenza disease burden studies.",2012 Jun 20,"['Wang, Xi-Ling', 'Yang, Lin', 'Chan, King-Pan', 'Chiu, Susan S.', 'Chan, Kwok-Hung', 'Peiris, J. S. Malik', 'Wong, Chit-Ming']",PLoS One,,,True
8d03e1689613cf8af353a27d62adaf44e1b20e67,PMC,Evolutionary Responses to a Constructed Niche: Ancient Mesoamericans as a Model of Gene-Culture Coevolution,http://dx.doi.org/10.1371/journal.pone.0038862,PMC3380856,22768049,CC BY,"Culture and genetics rely on two distinct but not isolated transmission systems. Cultural processes may change the human selective environment and thereby affect which individuals survive and reproduce. Here, we evaluated whether the modes of subsistence in Native American populations and the frequencies of the ABCA1*Arg230Cys polymorphism were correlated. Further, we examined whether the evolutionary consequences of the agriculturally constructed niche in Mesoamerica could be considered as a gene-culture coevolution model. For this purpose, we genotyped 229 individuals affiliated with 19 Native American populations and added data for 41 other Native American groups (n = 1905) to the analysis. In combination with the SNP cluster of a neutral region, this dataset was then used to unravel the scenario involved in 230Cys evolutionary history. The estimated age of 230Cys is compatible with its origin occurring in the American continent. The correlation of its frequencies with the archeological data on Zea pollen in Mesoamerica/Central America, the neutral coalescent simulations, and the F(ST)-based natural selection analysis suggest that maize domestication was the driving force in the increase in the frequencies of 230Cys in this region. These results may represent the first example of a gene-culture coevolution involving an autochthonous American allele.",2012 Jun 21,"['Hünemeier, Tábita', 'Amorim, Carlos Eduardo Guerra', 'Azevedo, Soledad', 'Contini, Veronica', 'Acuña-Alonzo, Víctor', 'Rothhammer, Francisco', 'Dugoujon, Jean-Michel', 'Mazières, Stephane', 'Barrantes, Ramiro', 'Villarreal-Molina, María Teresa', 'Paixão-Côrtes, Vanessa Rodrigues', 'Salzano, Francisco M.', 'Canizales-Quinteros, Samuel', 'Ruiz-Linares, Andres', 'Bortolini, Maria Cátira']",PLoS One,,,True
6c0431081c9d7d41d0efddd87fb0244b401ef67c,PMC,"Vulnerability, equity and universal coverage – a concept note",http://dx.doi.org/10.1186/1471-2458-12-S1-S2,PMC3381707,22992314,CC BY,,2012 Jun 22,"['Allotey, Pascale', 'Verghis, Sharuna', 'Alvarez-Castillo, Fatima', 'Reidpath, Daniel D']",BMC Public Health,,,True
687dd2bd2a0f74f0ef9383f75fb1147e28dfe1d6,PMC,"Differential Seroprevalence of Human Bocavirus Species 1-4 in Beijing, China",http://dx.doi.org/10.1371/journal.pone.0039644,PMC3382199,22761854,CC BY,"BACKGROUND: Four species of human bocaviruses (HBoV1-4) have been identified based on phylogenetic analysis since its first report in 2005. HBoV1 has been associated with respiratory disease, whereas HBoV2-4 are mainly detected in enteric infections. Although the prevalence of HBoVs in humans has been studied in some regions, it has not been well addressed globally. METHODOLOGY/PRINCIPAL FINDINGS: Cross-reactivity of anti-VP2 antibodies was detected between HBoV1, 2, 3, and 4 in mouse and human serum. The prevalence of specific anti-VP2 IgG antibodies against HBoV1-4 was determined in different age groups of healthy individuals aged 0-70 years old in Beijing, China, using a competition ELISA assay based on virus-like particles of HBoV1-4. The seroprevalence of HBoV1-4 was 50%, 36.9%, 28.7%, and 0.8%, respectively, in children aged 0-14 years (n = 244); whereas the seroprevalence of HBoV1-4 was 66.9%, 49.3%, 38.7% and 1.4%, respectively, in healthy adults (≥15 years old; n = 142). The seropositive rate of HBoV1 was higher than that of HBoV2, HBoV3, and HBoV4 in individuals older than 0.5 years. Furthermore, IgG seroconversion of HBoV1 (10/31, 32.3%), HBoV2 (8/31, 25.8%), and HBoV3 (2/31, 6.5%) was found in paired sera collected from children with respiratory tract infections who were positive for HBoV1 according to PCR analysis. CONCLUSIONS/SIGNIFICANCE: Our data indicate that HBoV1 is more prevalent than HBoV2, HBoV3, and HBoV4 in the population we sampled in Beijing, China, suggesting that HBoV species may play differential roles in disease.",2012 Jun 22,"['Guo, Li', 'Wang, Yaying', 'Zhou, Hongli', 'Wu, Chao', 'Song, Jingdong', 'Li, Jianguo', 'Paranhos-Baccalà, Gláucia', 'Vernet, Guy', 'Wang, Jianwei', 'Hung, Tao']",PLoS One,,,True
aae1603af1bb84087248441716a5c0bd373603b7,PMC,H1N1pdm09 Adjuvanted Vaccination in HIV-Infected Adults: A Randomized Trial of Two Single versus Two Double Doses,http://dx.doi.org/10.1371/journal.pone.0039310,PMC3382468,22761759,CC BY,"BACKGROUND: Since human immunodeficiency virus (HIV)-infected individuals are at increased risk of severe disease from pandemic influenza A (H1N1pdm09), vaccination was recommended as a prevention strategy. The aim of the present study was to evaluate the safety, immunogenicity and persistence of the immune response after vaccination against pandemic influenza A (H1N1pdm09) with an adjuvanted vaccine in human immunodeficiency virus (HIV)-infected adults using two single and two double doses. METHODOLOGY/PRINCIPAL FINDINGS: Open label, randomized trial to evaluate the immune response following H1N1pdm09 vaccination in HIV-infected participants compared to HIV-negative controls (NCT01155037). HIV-infected participants were randomized to receive 2 single (3.75 µg hemagglutinin) or 2 double (7.5 µg hemagglutinin) doses of the vaccine, 21 days apart. Controls received one dose of the vaccine. The primary endpoint was seroconversion as measured by hemagglutination inhibition assay. Two hundred fifty six HIV-infected participants (129 and 127 randomized to single and double doses, respectively) and 71 HIV-negative controls were enrolled. Among HIV-infected participants, seroconversion increased from 46.7% and 51.7% after the first dose to 77.2% and 83.8% after the second dose of the vaccine using single and double doses, respectively. Participants aged >40 years showed higher seroconversion compared to younger participants. Seroconversion among HIV-infected women and those with nadir CD4<200 cells/mm(3) was significantly higher with double doses. Persistence of protective antibodies six months after vaccination was achieved by 80% and 89.9% of the HIV-infected participants who received single and double doses, respectively. CONCLUSIONS/SIGNIFICANCE: Our results support the recommendation of two double doses of adjuvanted H1N1pdm09 vaccine for HIV-infected individuals, particularly women, and those aged >40 years or with nadir CD4<200 cells/mm(3), to achieve antibody levels that are both higher and more sustained. TRIAL REGISTRATION: ClinicalTrials.gov NCT01155037",2012 Jun 25,"['Santini-Oliveira, Marilia', 'Camacho, Luiz A. B.', 'Souza, Thiago M. L.', 'Luz, Paula M.', 'Vasconcellos, Mauricio T. L.', 'Giacoia-Gripp, Carmem B. W.', 'Morgado, Mariza G.', 'Nunes, Estevão P.', 'Lemos, Alberto S.', 'Ferreira, Ana C. G.', 'Moreira, Ronaldo I.', 'Veloso, Valdiléa G.', 'Siqueira, Marilda M.', 'Grinsztejn, Beatriz']",PLoS One,,,True
af400a711649c6703b915e8a935dfe778bc42132,PMC,H1N1pdm09 Adjuvanted Vaccination in HIV-Infected Adults: A Randomized Trial of Two Single versus Two Double Doses,http://dx.doi.org/10.1371/journal.pone.0039310,PMC3382468,22761759,CC BY,"BACKGROUND: Since human immunodeficiency virus (HIV)-infected individuals are at increased risk of severe disease from pandemic influenza A (H1N1pdm09), vaccination was recommended as a prevention strategy. The aim of the present study was to evaluate the safety, immunogenicity and persistence of the immune response after vaccination against pandemic influenza A (H1N1pdm09) with an adjuvanted vaccine in human immunodeficiency virus (HIV)-infected adults using two single and two double doses. METHODOLOGY/PRINCIPAL FINDINGS: Open label, randomized trial to evaluate the immune response following H1N1pdm09 vaccination in HIV-infected participants compared to HIV-negative controls (NCT01155037). HIV-infected participants were randomized to receive 2 single (3.75 µg hemagglutinin) or 2 double (7.5 µg hemagglutinin) doses of the vaccine, 21 days apart. Controls received one dose of the vaccine. The primary endpoint was seroconversion as measured by hemagglutination inhibition assay. Two hundred fifty six HIV-infected participants (129 and 127 randomized to single and double doses, respectively) and 71 HIV-negative controls were enrolled. Among HIV-infected participants, seroconversion increased from 46.7% and 51.7% after the first dose to 77.2% and 83.8% after the second dose of the vaccine using single and double doses, respectively. Participants aged >40 years showed higher seroconversion compared to younger participants. Seroconversion among HIV-infected women and those with nadir CD4<200 cells/mm(3) was significantly higher with double doses. Persistence of protective antibodies six months after vaccination was achieved by 80% and 89.9% of the HIV-infected participants who received single and double doses, respectively. CONCLUSIONS/SIGNIFICANCE: Our results support the recommendation of two double doses of adjuvanted H1N1pdm09 vaccine for HIV-infected individuals, particularly women, and those aged >40 years or with nadir CD4<200 cells/mm(3), to achieve antibody levels that are both higher and more sustained. TRIAL REGISTRATION: ClinicalTrials.gov NCT01155037",2012 Jun 25,"['Santini-Oliveira, Marilia', 'Camacho, Luiz A. B.', 'Souza, Thiago M. L.', 'Luz, Paula M.', 'Vasconcellos, Mauricio T. L.', 'Giacoia-Gripp, Carmem B. W.', 'Morgado, Mariza G.', 'Nunes, Estevão P.', 'Lemos, Alberto S.', 'Ferreira, Ana C. G.', 'Moreira, Ronaldo I.', 'Veloso, Valdiléa G.', 'Siqueira, Marilda M.', 'Grinsztejn, Beatriz']",PLoS One,,,True
0f48ba54e2976264796ac7496f9080b52568fb51,PMC,Respiratory viral pathogens associated with lower respiratory tract disease among young children in the highlands of Papua New Guinea,http://dx.doi.org/10.1016/j.jcv.2012.04.008,PMC3383990,22595309,CC BY,"BACKGROUND: Acute lower respiratory tract infections (ALRI) commonly result in fatal outcomes in the young children of Papua New Guinea (PNG). However, comprehensive studies of the viral aetiology of ALRI have not been conducted in PNG for almost 30 years. OBJECTIVES: To determine the viruses associated with ALRI among children living in the PNG highlands using sensitive molecular detection techniques. STUDY DESIGN: Pernasal swabs were collected routinely between 1 week and 18 months of age and also during episodes of ALRI, as part of a neonatal pneumococcal conjugate vaccine trial. A tandem multiplex real-time PCR assay was used to test for a comprehensive range of respiratory viruses in samples collected from 221 young children. Picornavirus typing was supported by DNA sequence analysis. RESULTS: Recognized pathogenic respiratory viruses were detected in 198/273 (73%) samples collected from children with no evidence of ALRI and 69/80 (86%) samples collected during ALRI episodes. Human rhinoviruses (HRV) species A, B and C were detected in 152 (56%) samples from non-ALRI children and 50 (63%) samples collected during ALRI episodes. Partial structural region sequences for two new species C rhinoviruses were added to the GenBank database. ALRI was associated with detection of adenovirus species B (p < 0.01) or C (p < 0.05), influenza A (p < 0.0001) or respiratory syncytial virus (p < 0.0001). Multiple viruses were detected more often during ALRI episodes (49%) than when children displayed no symptoms of ALRI (18%) (p < 0.0001). CONCLUSIONS: The burden of infection with respiratory viruses remains significant in young children living in the PNG highlands.",2012 Jul,"['Chidlow, Glenys R.', 'Laing, Ingrid A.', 'Harnett, Gerald B.', 'Greenhill, Andrew R.', 'Phuanukoonnon, Suparat', 'Siba, Peter M.', 'Pomat, William S.', 'Shellam, Geoffrey R.', 'Smith, David W.', 'Lehmann, Deborah']",J Clin Virol,,,False
5326626cf66eb61f7f001c6557c23058b57fb2e2,PMC,Clarithromycin Suppresses Human Respiratory Syncytial Virus Infection-Induced Streptococcus pneumoniae Adhesion and Cytokine Production in a Pulmonary Epithelial Cell Line,http://dx.doi.org/10.1155/2012/528568,PMC3384978,22761540,CC BY,"Human respiratory syncytial virus (RSV) sometimes causes acute and severe lower respiratory tract illness in infants and young children. RSV strongly upregulates proinflammatory cytokines and the platelet-activating factor (PAF) receptor, which is a receptor for Streptococcus pneumoniae, in the pulmonary epithelial cell line A549. Clarithromycin (CAM), which is an antimicrobial agent and is also known as an immunomodulator, significantly suppressed RSV-induced production of interleukin-6, interleukin-8, and regulated on activation, normal T-cell expressed and secreted (RANTES). CAM also suppressed RSV-induced PAF receptor expression and adhesion of fluorescein-labeled S. pneumoniae cells to A549 cells. The RSV-induced S. pneumoniae adhesion was thought to be mediated by the host cell's PAF receptor. CAM, which exhibits antimicrobial and immunomodulatory activities, was found in this study to suppress the RSV-induced adhesion of respiratory disease-causing bacteria, S. pneumoniae, to host cells. Thus, CAM might suppress immunological disorders and prevent secondary bacterial infections during RSV infection.",2012 Jun 12,"['Yokota, Shin-ichi', 'Okabayashi, Tamaki', 'Hirakawa, Satoshi', 'Tsutsumi, Hiroyuki', 'Himi, Tetsuo', 'Fujii, Nobuhiro']",Mediators Inflamm,,,True
72ddf8d0c71b8b1ece743904f2acd2c1a00984c4,PMC,Inferring pandemic growth rates from sequence data,http://dx.doi.org/10.1098/rsif.2011.0850,PMC3385754,22337627,CC BY,"Using sequence data to infer population dynamics is playing an increasing role in the analysis of outbreaks. The most common methods in use, based on coalescent inference, have been widely used but not extensively tested against simulated epidemics. Here, we use simulated data to test the ability of both parametric and non-parametric methods for inference of effective population size (coded in the popular BEAST package) to reconstruct epidemic dynamics. We consider a range of simulations centred on scenarios considered plausible for pandemic influenza, but our conclusions are generic for any exponentially growing epidemic. We highlight systematic biases in non-parametric effective population size estimation. The most prominent such bias leads to the false inference of slowing of epidemic spread in the recent past even when the real epidemic is growing exponentially. We suggest some sampling strategies that could reduce (but not eliminate) some of the biases. Parametric methods can correct for these biases if the infected population size is large. We also explore how some poor sampling strategies (e.g. that over-represent epidemiologically linked clusters of cases) could dramatically exacerbate bias in an uncontrolled manner. Finally, we present a simple diagnostic indicator, based on coalescent density and which can easily be applied to reconstructed phylogenies, that identifies time-periods for which effective population size estimates are less likely to be biased. We illustrate this with an application to the 2009 H1N1 pandemic.",2012 Aug 7,"['de Silva, Eric', 'Ferguson, Neil M.', 'Fraser, Christophe']",J R Soc Interface,,,True
47ee3efc99d4ed2a08a7c8e677adfd98425dade6,PMC,Regulatory T Cells in Arterivirus and Coronavirus Infections: Do They Protect Against Disease or Enhance it?,http://dx.doi.org/10.3390/v4050833,PMC3386620,22754651,CC BY,"Regulatory T cells (T(regs)) are a subset of T cells that are responsible for maintaining peripheral immune tolerance and homeostasis. The hallmark of T(regs) is the expression of the forkhead box P3 (FoxP3) transcription factor. Natural regulatory T cells (nT(regs)) are a distinct population of T cells that express CD4 and FoxP3. nTregs develop in the thymus and function in maintaining peripheral immune tolerance. Other CD4(+), CD4(-)CD8(-), and CD8(+)CD28(-) T cells can be induced to acquire regulatory function by antigenic stimulation, depending on the cytokine milieu. Inducible (or adaptive) T(regs) frequently express high levels of the interleukin 2 receptor (CD25). Atypical T(regs) express FoxP3 and CD4 but have no surface expression of CD25. Type 1 regulatory T cells (Tr1 cells) produce IL-10, while T helper 3 cells (Th3) produce TGF-β. The function of inducible T(regs) is presumably to maintain immune homeostasis, especially in the context of chronic inflammation or infection. Induction of T(regs) in coronaviral infections protects against the more severe forms of the disease attributable to the host response. However, arteriviruses have exploited these T cell subsets as a means to dampen the immune response allowing for viral persistence. T(reg) induction or activation in the pathogenesis of disease has been described in both porcine reproductive and respiratory syndrome virus, lactate dehydrogenase elevating virus, and mouse hepatitis virus. This review discusses the development and biology of regulatory T cells in the context of arteriviral and coronaviral infection.",2012 May 15,"['Cecere, Thomas E.', 'Todd, S. Michelle', 'LeRoith, Tanya']",Viruses,,,True
fd71de909bf3d6539246e78e650a76f6eb90b23b,PMC,Post-Transcriptional Control of Type I Interferon Induction by Porcine Reproductive and Respiratory Syndrome Virus in Its Natural Host Cells,http://dx.doi.org/10.3390/v4050725,PMC3386621,22754646,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) is not only a poor inducer of type I interferon but also inhibits the efficient induction of type I interferon by porcine transmissible gastroenteritis virus (TGEV) and synthetic dsRNA molecules, Poly I:C. However, the mechanistic basis by which PRRSV interferes with the induction of type I interferon in its natural host cells remains less well defined. The purposes of this review are to summarize the key findings in supporting the post-transcriptional control of type I interferon in its natural host cells and to propose the possible role of translational control in the regulation of type I interferon induction by PRRSV.",2012 May 2,"['Wang, Xiuqing', 'Christopher-Hennings, Jane']",Viruses,,,True
62f5729ba9ae176c206cafd0221804a80772ea37,PMC,Protective Role of Toll-like Receptor 3-Induced Type I Interferon in Murine Coronavirus Infection of Macrophages,http://dx.doi.org/10.3390/v4050901,PMC3386628,22754655,CC BY,"Toll-like Receptors (TLRs) sense viral infections and induce production of type I interferons (IFNs), other cytokines, and chemokines. Viral recognition by TLRs and other pattern recognition receptors (PRRs) has been proven to be cell-type specific. Triggering of TLRs with selected ligands can be beneficial against some viral infections. Macrophages are antigen-presenting cells that express TLRs and have a key role in the innate and adaptive immunity against viruses. Coronaviruses (CoVs) are single-stranded, positive-sense RNA viruses that cause acute and chronic infections and can productively infect macrophages. Investigation of the interplay between CoVs and PRRs is in its infancy. We assessed the effect of triggering TLR2, TLR3, TLR4, and TLR7 with selected ligands on the susceptibility of the J774A.1 macrophage cell line to infection with murine coronavirus (mouse hepatitis virus, [MHV]). Stimulation of TLR2, TLR4, or TLR7 did not affect MHV production. In contrast, pre-stimulation of TLR3 with polyinosinic-polycytidylic acid (poly I:C) hindered MHV infection through induction of IFN-β in macrophages. We demonstrate that activation of TLR3 with the synthetic ligand poly I:C mediates antiviral immunity that diminishes (MHV-A59) or suppresses (MHV-JHM, MHV-3) virus production in macrophages.",2012 May 24,"['Mazaleuskaya, Liudmila', 'Veltrop, Rogier', 'Ikpeze, Nneka', 'Martin-Garcia, Julio', 'Navas-Martin, Sonia']",Viruses,,,True
ea4880d01d03a59bb3de58e8ae226c5487e38e6c,PMC,Comprehensive Biothreat Cluster Identification by PCR/Electrospray-Ionization Mass Spectrometry,http://dx.doi.org/10.1371/journal.pone.0036528,PMC3387173,22768032,CC0,"Technology for comprehensive identification of biothreats in environmental and clinical specimens is needed to protect citizens in the case of a biological attack. This is a challenge because there are dozens of bacterial and viral species that might be used in a biological attack and many have closely related near-neighbor organisms that are harmless. The biothreat agent, along with its near neighbors, can be thought of as a biothreat cluster or a biocluster for short. The ability to comprehensively detect the important biothreat clusters with resolution sufficient to distinguish the near neighbors with an extremely low false positive rate is required. A technological solution to this problem can be achieved by coupling biothreat group-specific PCR with electrospray ionization mass spectrometry (PCR/ESI-MS). The biothreat assay described here detects ten bacterial and four viral biothreat clusters on the NIAID priority pathogen and HHS/USDA select agent lists. Detection of each of the biothreat clusters was validated by analysis of a broad collection of biothreat organisms and near neighbors prepared by spiking biothreat nucleic acids into nucleic acids extracted from filtered environmental air. Analytical experiments were carried out to determine breadth of coverage, limits of detection, linearity, sensitivity, and specificity. Further, the assay breadth was demonstrated by testing a diverse collection of organisms from each biothreat cluster. The biothreat assay as configured was able to detect all the target organism clusters and did not misidentify any of the near-neighbor organisms as threats. Coupling biothreat cluster-specific PCR to electrospray ionization mass spectrometry simultaneously provides the breadth of coverage, discrimination of near neighbors, and an extremely low false positive rate due to the requirement that an amplicon with a precise base composition of a biothreat agent be detected by mass spectrometry.",2012 Jun 29,"['Sampath, Rangarajan', 'Mulholland, Niveen', 'Blyn, Lawrence B.', 'Massire, Christian', 'Whitehouse, Chris A.', 'Waybright, Nicole', 'Harter, Courtney', 'Bogan, Joseph', 'Miranda, Mary Sue', 'Smith, David', 'Baldwin, Carson', 'Wolcott, Mark', 'Norwood, David', 'Kreft, Rachael', 'Frinder, Mark', 'Lovari, Robert', 'Yasuda, Irene', 'Matthews, Heather', 'Toleno, Donna', 'Housley, Roberta', 'Duncan, David', 'Li, Feng', 'Warren, Robin', 'Eshoo, Mark W.', 'Hall, Thomas A.', 'Hofstadler, Steven A.', 'Ecker, David J.']",PLoS One,,,True
28bec3efe92c8567992ee35baecf2dc42bbc34ae,PMC,Comparative analysis of mycobacterium and related actinomycetes yields insight into the evolution of mycobacterium tuberculosis pathogenesis,http://dx.doi.org/10.1186/1471-2164-13-120,PMC3388012,22452820,CC BY,"BACKGROUND: The sequence of the pathogen Mycobacterium tuberculosis (Mtb) strain H37Rv has been available for over a decade, but the biology of the pathogen remains poorly understood. Genome sequences from other Mtb strains and closely related bacteria present an opportunity to apply the power of comparative genomics to understand the evolution of Mtb pathogenesis. We conducted a comparative analysis using 31 genomes from the Tuberculosis Database (TBDB.org), including 8 strains of Mtb and M. bovis, 11 additional Mycobacteria, 4 Corynebacteria, 2 Streptomyces, Rhodococcus jostii RHA1, Nocardia farcinia, Acidothermus cellulolyticus, Rhodobacter sphaeroides, Propionibacterium acnes, and Bifidobacterium longum. RESULTS: Our results highlight the functional importance of lipid metabolism and its regulation, and reveal variation between the evolutionary profiles of genes implicated in saturated and unsaturated fatty acid metabolism. It also suggests that DNA repair and molybdopterin cofactors are important in pathogenic Mycobacteria. By analyzing sequence conservation and gene expression data, we identify nearly 400 conserved noncoding regions. These include 37 predicted promoter regulatory motifs, of which 14 correspond to previously validated motifs, as well as 50 potential noncoding RNAs, of which we experimentally confirm the expression of four. CONCLUSIONS: Our analysis of protein evolution highlights gene families that are associated with the adaptation of environmental Mycobacteria to obligate pathogenesis. These families include fatty acid metabolism, DNA repair, and molybdopterin biosynthesis. Our analysis reinforces recent findings suggesting that small noncoding RNAs are more common in Mycobacteria than previously expected. Our data provide a foundation for understanding the genome and biology of Mtb in a comparative context, and are available online and through TBDB.org.",2012 Mar 28,"['McGuire, Abigail Manson', 'Weiner, Brian', 'Park, Sang Tae', 'Wapinski, Ilan', 'Raman, Sahadevan', 'Dolganov, Gregory', 'Peterson, Matthew', 'Riley, Robert', 'Zucker, Jeremy', 'Abeel, Thomas', 'White, Jared', 'Sisk, Peter', 'Stolte, Christian', 'Koehrsen, Mike', 'Yamamoto, Robert T', 'Iacobelli-Martinez, Milena', 'Kidd, Matthew J', 'Maer, Andreia M', 'Schoolnik, Gary K', 'Regev, Aviv', 'Galagan, James']",BMC Genomics,,,True
b3b492aee17ce67199d458de9b98bc219c2cbf3c,PMC,Estrogen Mediates Innate and Adaptive Immune Alterations to Influenza Infection in Pregnant Mice,http://dx.doi.org/10.1371/journal.pone.0040502,PMC3390370,22792357,CC BY,"Pregnancy is a leading risk factor for severe complications during an influenza virus infection. Women infected during their second and third trimesters are at increased risk for severe cardiopulmonary complications, premature delivery, and death. Here, we establish a murine model of aerosolized influenza infection during pregnancy. We find significantly altered innate antiviral responses in pregnant mice, including decreased levels of IFN-β, IL-1α, and IFN-γ at early time points of infection. We also find reduced cytotoxic T cell activity and delayed viral clearance. We further demonstrate that pregnancy levels of the estrogen 17-β-estradiol are able to induce key anti-inflammatory phenotypes in immune responses to the virus independently of other hormones or pregnancy-related stressors. We conclude that elevated estrogen levels result in an attenuated anti-viral immune response, and that pregnancy-associated morbidities occur in the context of this anti-inflammatory phenotype.",2012 Jul 5,"['Pazos, Michael A.', 'Kraus, Thomas A.', 'Muñoz-Fontela, César', 'Moran, Thomas M.']",PLoS One,,,True
5ae7223cc6ab3437ba262bb2bb47768948e01d59,PMC,Proteasome-Dependent Disruption of the E3 Ubiquitin Ligase Anaphase-Promoting Complex by HCMV Protein pUL21a,http://dx.doi.org/10.1371/journal.ppat.1002789,PMC3390409,22792066,CC BY,"The anaphase-promoting complex (APC) is an E3 ubiquitin ligase which controls ubiquitination and degradation of multiple cell cycle regulatory proteins. During infection, human cytomegalovirus (HCMV), a widespread pathogen, not only phosphorylates the APC coactivator Cdh1 via the multifunctional viral kinase pUL97, it also promotes degradation of APC subunits via an unknown mechanism. Using a proteomics approach, we found that a recently identified HCMV protein, pUL21a, interacted with the APC. Importantly, we determined that expression of pUL21a was necessary and sufficient for proteasome-dependent degradation of APC subunits APC4 and APC5. This resulted in APC disruption and required pUL21a binding to the APC. We have identified the proline-arginine amino acid pair at residues 109–110 in pUL21a to be critical for its ability to bind and regulate the APC. A point mutant virus in which proline-arginine were mutated to alanines (PR-AA) grew at wild-type levels. However, a double mutant virus in which the viral ability to regulate the APC was abrogated by both PR-AA point mutation and UL97 deletion was markedly more attenuated compared to the UL97 deletion virus alone. This suggests that these mutations are synthetically lethal, and that HCMV exploits two viral factors to ensure successful disruption of the APC to overcome its restriction on virus infection. This study reveals the HCMV protein pUL21a as a novel APC regulator and uncovers a unique viral mechanism to subvert APC activity.",2012 Jul 5,"['Fehr, Anthony R.', 'Gualberto, Nathaniel C.', 'Savaryn, John Paul', 'Terhune, Scott S.', 'Yu, Dong']",PLoS Pathog,,,True
f6b79474869aa89ef3a3cab01f39abac279c5132,PMC,Proteomic Profiling of the TRAF3 Interactome Network Reveals a New Role for the ER-to-Golgi Transport Compartments in Innate Immunity,http://dx.doi.org/10.1371/journal.ppat.1002747,PMC3390413,22792062,CC BY,"Tumor Necrosis Factor receptor-associated factor-3 (TRAF3) is a central mediator important for inducing type I interferon (IFN) production in response to intracellular double-stranded RNA (dsRNA). Here, we report the identification of Sec16A and p115, two proteins of the ER-to-Golgi vesicular transport system, as novel components of the TRAF3 interactome network. Notably, in non-infected cells, TRAF3 was found associated with markers of the ER-Exit-Sites (ERES), ER-to-Golgi intermediate compartment (ERGIC) and the cis-Golgi apparatus. Upon dsRNA and dsDNA sensing however, the Golgi apparatus fragmented into cytoplasmic punctated structures containing TRAF3 allowing its colocalization and interaction with Mitochondrial AntiViral Signaling (MAVS), the essential mitochondria-bound RIG-I-like Helicase (RLH) adaptor. In contrast, retention of TRAF3 at the ER-to-Golgi vesicular transport system blunted the ability of TRAF3 to interact with MAVS upon viral infection and consequently decreased type I IFN response. Moreover, depletion of Sec16A and p115 led to a drastic disorganization of the Golgi paralleled by the relocalization of TRAF3, which under these conditions was unable to associate with MAVS. Consequently, upon dsRNA and dsDNA sensing, ablation of Sec16A and p115 was found to inhibit IRF3 activation and anti-viral gene expression. Reciprocally, mild overexpression of Sec16A or p115 in Hec1B cells increased the activation of IFNβ, ISG56 and NF-κB -dependent promoters following viral infection and ectopic expression of MAVS and Tank-binding kinase-1 (TBK1). In line with these results, TRAF3 was found enriched in immunocomplexes composed of p115, Sec16A and TBK1 upon infection. Hence, we propose a model where dsDNA and dsRNA sensing induces the formation of membrane-bound compartments originating from the Golgi, which mediate the dynamic association of TRAF3 with MAVS leading to an optimal induction of innate immune responses.",2012 Jul 5,"['van Zuylen, Wendy J.', 'Doyon, Priscilla', 'Clément, Jean-François', 'Khan, Kashif Aziz', ""D'Ambrosio, Lisa M."", 'Dô, Florence', 'St-Amant-Verret, Myriam', 'Wissanji, Tasheen', 'Emery, Gregory', 'Gingras, Anne-Claude', 'Meloche, Sylvain', 'Servant, Marc J.']",PLoS Pathog,,,True
db01b3a1badd793717ba425dc52f976f0212e763,PMC,"The Four Horsemen of the Apocalypse: Tropical Medicine in the Fight against Plague, Death, Famine, and War",http://dx.doi.org/10.4269/ajtmh.2012.11-0814,PMC3391054,22764283,CC BY,,2012 Jul 1,"Hotez, Peter J.",Am J Trop Med Hyg,,,True
778543806bc7ebe5596c085cf9a0421d0c0a1a2f,PMC,Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery,http://dx.doi.org/10.1371/journal.pone.0040662,PMC3393700,22808228,CC BY,"The innate ability of the human cell to silence endogenous retroviruses through RNA sequences encoding microRNAs, suggests that the cellular RNAi machinery is a major means by which the host mounts a defense response against present day retroviruses. Indeed, cellular miRNAs target and hybridize to specific sequences of both HTLV-1 and HIV-1 viral transcripts. However, much like the variety of host immune responses to retroviral infection, the virus itself contains mechanisms that assist in the evasion of viral inhibition through control of the cellular RNAi pathway. Retroviruses can hijack both the enzymatic and catalytic components of the RNAi pathway, in some cases to produce novel viral miRNAs that can either assist in active viral infection or promote a latent state. Here, we show that HTLV-1 Tax contributes to the dysregulation of the RNAi pathway by altering the expression of key components of this pathway. A survey of uninfected and HTLV-1 infected cells revealed that Drosha protein is present at lower levels in all HTLV-1 infected cell lines and in infected primary cells, while other components such as DGCR8 were not dramatically altered. We show colocalization of Tax and Drosha in the nucleus in vitro as well as coimmunoprecipitation in the presence of proteasome inhibitors, indicating that Tax interacts with Drosha and may target it to specific areas of the cell, namely, the proteasome. In the presence of Tax we observed a prevention of primary miRNA cleavage by Drosha. Finally, the changes in cellular miRNA expression in HTLV-1 infected cells can be mimicked by the add back of Drosha or the addition of antagomiRs against the cellular miRNAs which are downregulated by the virus.",2012 Jul 10,"['Van Duyne, Rachel', 'Guendel, Irene', 'Klase, Zachary', 'Narayanan, Aarthi', 'Coley, William', 'Jaworski, Elizabeth', 'Roman, Jessica', 'Popratiloff, Anastas', 'Mahieux, Renaud', 'Kehn-Hall, Kylene', 'Kashanchi, Fatah']",PLoS One,,,True
d5878fe0a378d553186b212eeaadaa60257e933f,PMC,"Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission",http://dx.doi.org/10.1371/journal.pone.0040706,PMC3393705,22808239,CC BY,"BACKGROUND: Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Dendritic cell–specific ICAM-3 grabbing-nonintegrin (DC-SIGN, also known as CD209) is an HIV-1 receptor that enhances its transmission to T cells and is expressed on placental macrophages. METHODS AND FINDINGS: We have investigated the association between DC-SIGN genetic variants and risk of MTCT of HIV-1 among Zimbabwean infants and characterized the impact of the associated mutations on DC-SIGN expression and interaction with HIV-1. DC-SIGN promoter (p-336C and p-201A) and exon 4 (198Q and 242V) variants were all significantly associated with increased risk of intrauterine (IU) HIV-1 infection. Promoter variants decreased DC-SIGN expression both in vitro and in placental CD163(+) macrophages (Hofbauer cells) of HIV-1 unexposed infants but not of HIV-1 exposed infants. The exon 4 protein-modifying mutations increased HIV-1 capture and transmission to T cells in vitro. CONCLUSION: This study provides compelling evidence to support an important role of DC-SIGN in IU HIV-1 infection.",2012 Jul 10,"['Boily-Larouche, Geneviève', 'Milev, Miroslav P.', 'Zijenah, Lynn S.', 'Labbé, Annie-Claude', 'Zannou, Djimon M.', 'Humphrey, Jean H.', 'Ward, Brian J.', 'Poudrier, Johanne', 'Mouland, Andrew J.', 'Cohen, Éric A.', 'Roger, Michel']",PLoS One,,,True
3c787e585321cc1d3d62aacb1c74713a4c77e9cc,PMC,A New Model for Hendra Virus Encephalitis in the Mouse,http://dx.doi.org/10.1371/journal.pone.0040308,PMC3393746,22808132,CC BY,"Hendra virus (HeV) infection in humans is characterized by an influenza like illness, which may progress to pneumonia or encephalitis and lead to death. The pathogenesis of HeV infection is poorly understood, and the lack of a mouse model has limited the opportunities for pathogenetic research. In this project we reassessed the role of mice as an animal model for HeV infection and found that mice are susceptible to HeV infection after intranasal exposure, with aged mice reliably developing encephalitic disease. We propose an anterograde route of neuroinvasion to the brain, possibly along olfactory nerves. This is supported by evidence for the development of encephalitis in the absence of viremia and the sequential distribution of viral antigen along pathways of olfaction in the brain of intranasally challenged animals. In our studies mice developed transient lower respiratory tract infection without progressing to viremia and systemic vasculitis that is common to other animal models. These studies report a new animal model of HeV encephalitis that will allow more detailed studies of the neuropathogenesis of HeV infection, particularly the mode of viral spread and possible sequestration within the central nervous system; investigation of mechanisms that moderate the development of viremia and systemic disease; and inform the development of improved treatment options for human patients.",2012 Jul 10,"['Dups, Johanna', 'Middleton, Deborah', 'Yamada, Manabu', 'Monaghan, Paul', 'Long, Fenella', 'Robinson, Rachel', 'Marsh, Glenn A.', 'Wang, Lin-Fa']",PLoS One,,,True
6fc6b211d30d357b07a3d6de138a6964363ef154,PMC,Retroviral Env Glycoprotein Trafficking and Incorporation into Virions,http://dx.doi.org/10.1155/2012/682850,PMC3395148,22811910,CC BY,"Together with the Gag protein, the Env glycoprotein is a major retroviral structural protein and is essential for forming infectious virus particles. Env is synthesized, processed, and transported to certain microdomains at the plasma membrane and takes advantage of the same host machinery for its trafficking as that used by cellular glycoproteins. Incorporation of Env into progeny virions is probably mediated by the interaction between Env and Gag, in some cases with the additional involvement of certain host factors. Although several general models have been proposed to explain the incorporation of retroviral Env glycoproteins into virions, the actual mechanism for this process is still unclear, partly because structural data on the Env protein cytoplasmic tail is lacking. This paper presents the current understanding of the synthesis, trafficking, and virion incorporation of retroviral Env proteins.",2012 Jul 2,"Murakami, Tsutomu",Mol Biol Int,,,True
58f93bf42d2c4e21ed8effe492719d992849eff6,PMC,"Production, Characterization and Applications for Toxoplasma gondii-Specific Polyclonal Chicken Egg Yolk Immunoglobulins",http://dx.doi.org/10.1371/journal.pone.0040391,PMC3395712,22808150,CC BY,"BACKGROUND: Toxoplasma gondii may cause abortions, ocular and neurological disorders in warm-blood hosts. Immunized mammals are a wide source of hyperimmune sera used in different approaches, including diagnosis and the study of host-parasite interactions. Unfortunately, mammalian antibodies present limitations for its production, such as the necessity for animal bleeding, low yield, interference with rheumatoid factor, complement activation and affinity to Fc mammalian receptors. IgY antibodies avoid those limitations; therefore they could be an alternative to be applied in T. gondii model. METHODOLOGY/PRINCIPAL FINDINGS: In this study we immunized hens with soluble tachyzoite antigens of T. gondii (STAg) and purified egg yolk antibodies (IgY) by an inexpensive and simple method, with high yield and purity degree. IgY anti-STAg antibodies presented high avidity and were able to recognize a broad range of parasite antigens, although some marked differences were observed in reactivity profile between antibodies produced in immunized hens and mice. Interestingly, IgY antibodies against Neospora caninum and Eimeria spp. did not react to STAg. We also show that IgY antibodies were suitable to detect T. gondii forms in paraffin-embedded sections and culture cell monolayers. CONCLUSIONS/SIGNIFICANCE: Due to its cost-effectiveness, high production yield and varied range of possible applications, polyclonal IgY antibodies are useful tools for studies involving T. gondii.",2012 Jul 12,"['Ferreira Júnior, Álvaro', 'Santiago, Fernanda M.', 'Silva, Murilo V.', 'Ferreira, Flávia B.', 'Macêdo Júnior, Arlindo G.', 'Mota, Caroline M.', 'Faria, Matheus S.', 'Filho, Hercílio H. Silva', 'Silva, Deise A. O.', 'Cunha-Júnior, Jair P.', 'Mineo, José R.', 'Mineo, Tiago W. P.']",PLoS One,,,True
f5e974ef3a8c983ae63ac4f4aa2b6ec0e3678032,PMC,Recent Progress in Studies of Arterivirus- and Coronavirus-Host Interactions,http://dx.doi.org/10.3390/v4060980,PMC3397358,22816036,CC BY,"Animal coronaviruses, such as infectious bronchitis virus (IBV), and arteriviruses, such as porcine reproductive and respiratory syndrome virus (PRRSV), are able to manifest highly contagious infections in their specific native hosts, thereby arising in critical economic damage to animal industries. This review discusses recent progress in studies of virus-host interactions during animal and human coronavirus and arterivirus infections, with emphasis on IBV-host cell interactions. These interactions may be directly involved in viral replication or lead to the alteration of certain signaling pathways, such as cell stress response and innate immunity, to facilitate viral replication and pathogenesis.",2012 Jun 19,"['Zhong, Yanxin', 'Tan, Yong Wah', 'Liu, Ding Xiang']",Viruses,,,True
55ef87ca0d0cdad3973a94294211e8e9ea8bcc87,PMC,Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein,http://dx.doi.org/10.3390/v4061011,PMC3397359,22816037,CC BY,"Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. It is classified as a class I fusion protein, and is responsible for binding to the receptor on the host cell as well as mediating the fusion of host and viral membranes—A process driven by major conformational changes of the S protein. This review discusses coronavirus entry mechanisms focusing on the different triggers used by coronaviruses to initiate the conformational change of the S protein: receptor binding, low pH exposure and proteolytic activation. We also highlight commonalities between coronavirus S proteins and other class I viral fusion proteins, as well as distinctive features that confer distinct tropism, pathogenicity and host interspecies transmission characteristics to coronaviruses.",2012 Jun 20,"['Belouzard, Sandrine', 'Millet, Jean K.', 'Licitra, Beth N.', 'Whittaker, Gary R.']",Viruses,,,True
08dd1169c7aa45621e5f48bf6246b049e071e445,PMC,Evaluation of Four Different Systems for Extraction of RNA from Stool Suspensions Using MS-2 Coliphage as an Exogenous Control for RT-PCR Inhibition,http://dx.doi.org/10.1371/journal.pone.0039455,PMC3397973,22815706,CC BY,"Knowing when, and to what extent co-extracted inhibitors interfere with molecular RNA diagnostic assays is of utmost importance. The QIAamp Viral RNA Mini Kit (A); MagNA Pure LC2.0 Automatic extractor (B); KingFisher (C); and NucliSENS EasyMag (D) RNA extraction systems were evaluated for extraction efficiency and co-purification of inhibitors from stool suspensions. Real-Time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) of MS-2 coliphage spiked into each system’s lysis buffer served as an external control for both. Cycle thresholds (Cts) of the MS2 were determined for RNA extracted from stool suspensions containing unknown (n = 93) or varying amounts of inhibitors (n = 92). Stool suspensions from the latter group were also used to determine whether MS-2 and enterovirus rRT-PCR inhibitions were correlated. Specifically 23 RNA extracts from stool suspensions were spiked with enterovirus RNA after extraction and 13 of these stool suspension were spiked with intact enterovirus before extraction. MS2 rRT-PCR inhibition varied for RNAs extracted by the different systems. Inhibition was noted in 12 (13.0%), 26 (28.3%), 7 (7.6%), and 7 (7.6%) of the first 93 RNA extracts, and 58 (63.0%), 55 (59.8%), 37 (40.2%) and 30 (32.6%) of the second 92 extracts for A, B, C, and D, respectively. Furthermore, enterovirus rRT-PCR inhibition correlated with MS2 rRT-PCR inhibition for added enterovirus RNA or virus particles. In conclusion, rRT-PCR for MS-2 RNA is a good predictor of inhibition of enterovirus RNA extracted from stool suspensions. EasyMag performed the best, however all four extraction methods were suitable provided that external controls identified problematic samples.",2012 Jul 16,"['Shulman, Lester M.', 'Hindiyeh, Musa', 'Muhsen, Khitam', 'Cohen, Dani', 'Mendelson, Ella', 'Sofer, Danit']",PLoS One,,,True
1997909a084ca1b2b76a4f13bdcc9a320058db13,PMC,Evaluation of Four Different Systems for Extraction of RNA from Stool Suspensions Using MS-2 Coliphage as an Exogenous Control for RT-PCR Inhibition,http://dx.doi.org/10.1371/journal.pone.0039455,PMC3397973,22815706,CC BY,"Knowing when, and to what extent co-extracted inhibitors interfere with molecular RNA diagnostic assays is of utmost importance. The QIAamp Viral RNA Mini Kit (A); MagNA Pure LC2.0 Automatic extractor (B); KingFisher (C); and NucliSENS EasyMag (D) RNA extraction systems were evaluated for extraction efficiency and co-purification of inhibitors from stool suspensions. Real-Time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) of MS-2 coliphage spiked into each system’s lysis buffer served as an external control for both. Cycle thresholds (Cts) of the MS2 were determined for RNA extracted from stool suspensions containing unknown (n = 93) or varying amounts of inhibitors (n = 92). Stool suspensions from the latter group were also used to determine whether MS-2 and enterovirus rRT-PCR inhibitions were correlated. Specifically 23 RNA extracts from stool suspensions were spiked with enterovirus RNA after extraction and 13 of these stool suspension were spiked with intact enterovirus before extraction. MS2 rRT-PCR inhibition varied for RNAs extracted by the different systems. Inhibition was noted in 12 (13.0%), 26 (28.3%), 7 (7.6%), and 7 (7.6%) of the first 93 RNA extracts, and 58 (63.0%), 55 (59.8%), 37 (40.2%) and 30 (32.6%) of the second 92 extracts for A, B, C, and D, respectively. Furthermore, enterovirus rRT-PCR inhibition correlated with MS2 rRT-PCR inhibition for added enterovirus RNA or virus particles. In conclusion, rRT-PCR for MS-2 RNA is a good predictor of inhibition of enterovirus RNA extracted from stool suspensions. EasyMag performed the best, however all four extraction methods were suitable provided that external controls identified problematic samples.",2012 Jul 16,"['Shulman, Lester M.', 'Hindiyeh, Musa', 'Muhsen, Khitam', 'Cohen, Dani', 'Mendelson, Ella', 'Sofer, Danit']",PLoS One,,,False
35b637a1564ebf2f7d89ba7196a2cee30bdc9b0c,PMC,Evaluation of Four Different Systems for Extraction of RNA from Stool Suspensions Using MS-2 Coliphage as an Exogenous Control for RT-PCR Inhibition,http://dx.doi.org/10.1371/journal.pone.0039455,PMC3397973,22815706,CC BY,"Knowing when, and to what extent co-extracted inhibitors interfere with molecular RNA diagnostic assays is of utmost importance. The QIAamp Viral RNA Mini Kit (A); MagNA Pure LC2.0 Automatic extractor (B); KingFisher (C); and NucliSENS EasyMag (D) RNA extraction systems were evaluated for extraction efficiency and co-purification of inhibitors from stool suspensions. Real-Time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) of MS-2 coliphage spiked into each system’s lysis buffer served as an external control for both. Cycle thresholds (Cts) of the MS2 were determined for RNA extracted from stool suspensions containing unknown (n = 93) or varying amounts of inhibitors (n = 92). Stool suspensions from the latter group were also used to determine whether MS-2 and enterovirus rRT-PCR inhibitions were correlated. Specifically 23 RNA extracts from stool suspensions were spiked with enterovirus RNA after extraction and 13 of these stool suspension were spiked with intact enterovirus before extraction. MS2 rRT-PCR inhibition varied for RNAs extracted by the different systems. Inhibition was noted in 12 (13.0%), 26 (28.3%), 7 (7.6%), and 7 (7.6%) of the first 93 RNA extracts, and 58 (63.0%), 55 (59.8%), 37 (40.2%) and 30 (32.6%) of the second 92 extracts for A, B, C, and D, respectively. Furthermore, enterovirus rRT-PCR inhibition correlated with MS2 rRT-PCR inhibition for added enterovirus RNA or virus particles. In conclusion, rRT-PCR for MS-2 RNA is a good predictor of inhibition of enterovirus RNA extracted from stool suspensions. EasyMag performed the best, however all four extraction methods were suitable provided that external controls identified problematic samples.",2012 Jul 16,"['Shulman, Lester M.', 'Hindiyeh, Musa', 'Muhsen, Khitam', 'Cohen, Dani', 'Mendelson, Ella', 'Sofer, Danit']",PLoS One,,,False
e4722dbdd2d7a467fcfd82700a2493e5ee6efd9e,PMC,Reduction in Clostridium difficile Infection Rates after Mandatory Hospital Public Reporting: Findings from a Longitudinal Cohort Study in Canada,http://dx.doi.org/10.1371/journal.pmed.1001268,PMC3398960,22815656,CC BY,"BACKGROUND: The role of public reporting in improving hospital quality of care is controversial. Reporting of hospital-acquired infection rates has been introduced in multiple health care systems, but its relationship to infection rates has been understudied. Our objective was to determine whether mandatory public reporting by hospitals is associated with a reduction in hospital rates of Clostridium difficile infection. METHODS AND FINDINGS: We conducted a longitudinal, population-based cohort study in Ontario (Canada's largest province) between April 1, 2002, and March 31, 2010. We included all patients (>1 y old) admitted to 180 acute care hospitals. Using Poisson regression, we developed a model to predict hospital- and age-specific monthly rates of C. difficile disease per 10,000 patient-days prior to introduction of public reporting on September 1, 2008. We then compared observed monthly rates of C. difficile infection in the post-intervention period with rates predicted by the pre-intervention predictive model. In the pre-intervention period there were 33,634 cases of C. difficile infection during 39,221,113 hospital days, with rates increasing from 7.01 per 10,000 patient-days in 2002 to 10.79 in 2007. In the first calendar year after the introduction of public reporting, there was a decline in observed rates of C. difficile colitis in Ontario to 8.92 cases per 10,000 patient-days, which was significantly lower than the predicted rate of 12.16 (95% CI 11.35–13.04) cases per 10,000 patient-days (p<0.001). Over this period, public reporting was associated with a 26.7% (95% CI 21.4%–31.6%) reduction in C. difficile cases, or a projected 1,970 cases averted per year (95% CI 1,476–2,500). The effect was specific to C. difficile, with rates of community-acquired gastrointestinal infections and urinary tract infections unchanged. A limitation of our study is that this observational study design cannot rule out the influence of unmeasured temporal confounders. CONCLUSIONS: Public reporting of hospital C. difficile rates was associated with a substantial reduction in the population burden of this infection. Future research will be required to discern the direct mechanism by which C. difficile infection rates may have been reduced in response to public reporting. Please see later in the article for the Editors' Summary",2012 Jul 17,"['Daneman, Nick', 'Stukel, Therese A.', 'Ma, Xiaomu', 'Vermeulen, Marian', 'Guttmann, Astrid']",PLoS Med,,,True
c229a350536a9e087003fb14e9e52aab0245d2ec,PMC,Exploring IRES Region Accessibility by Interference of Foot-and-Mouth Disease Virus Infectivity,http://dx.doi.org/10.1371/journal.pone.0041382,PMC3399821,22815996,CC BY,"Translation initiation of picornavirus RNA is driven by an internal ribosome entry site (IRES) element located upstream of the initiator codon. RNA structure organization as well as RNA-protein interaction plays a fundamental role in internal initiation. IRES activity has been mainly analyzed in the context of reporter genes, lacking regions of the viral genome potentially affecting translation efficiency. With the aim to understand the vulnerability of the IRES and translation start region to small molecules in the context of the viral genome, we designed a set of customized RNase-resistant 2′O-methyl antisense oligoribonucleotides (2′OMe AONs) based on RNA structure data. These AONs were then used to monitor their capacity to interfere viral RNA translation, and thus, to inhibit virus yield. Foot-and-mouth disease virus (FMDV) RNA translation can be initiated at two in-frame AUG codons. We show here that a 2′OMe AON complementary to AUG2 inhibited viral multiplication more efficiently than the one that targeted AUG1. Furthermore, the response of the viral RNA to AONs targeting the IRES region denoted important differences between tissue culture cells and cell-free systems, reinforcing the need to analyze viral RNA response in living cells. Importantly, we have identified four specific motifs within the IRES element that are targets for viral inhibitors both in tissue culture cells and in cell-free systems. The identified targets define accessible regions to small molecules, which disturb either the RNA structural organization or the RNA-protein interactions needed to initiate translation in FMDV RNA.",2012 Jul 18,"['Fajardo, Teodoro', 'Rosas, Maria Flora', 'Sobrino, Francisco', 'Martinez-Salas, Encarnacion']",PLoS One,,,True
9d2c6b24e096eac147115b77f295e0ddcb5435c6,PMC,Molecular Imaging Reveals a Progressive Pulmonary Inflammation in Lower Airways in Ferrets Infected with 2009 H1N1 Pandemic Influenza Virus,http://dx.doi.org/10.1371/journal.pone.0040094,PMC3401186,22911695,CC BY,"Molecular imaging has gained attention as a possible approach for the study of the progression of inflammation and disease dynamics. Herein we used [(18)F]-2-deoxy-2-fluoro-D-glucose ([(18)F]-FDG) as a radiotracer for PET imaging coupled with CT (FDG-PET/CT) to gain insight into the spatiotemporal progression of the inflammatory response of ferrets infected with a clinical isolate of a pandemic influenza virus, H1N1 (H1N1pdm). The thoracic regions of mock- and H1N1pdm-infected ferrets were imaged prior to infection and at 1, 2, 3 and 6 days post-infection (DPI). On 1 DPI, FDG-PET/CT imaging revealed areas of consolidation in the right caudal lobe which corresponded with elevated [(18)F]-FDG uptake (maximum standardized uptake values (SUVMax), 4.7–7.0). By days 2 and 3, consolidation (CT) and inflammation ([(18)F]-FDG) appeared in the left caudal lobe. By 6 DPI, CT images showed extensive areas of patchy ground-glass opacities (GGO) and consolidations with the largest lesions having high SUVMax (6.0–7.6). Viral shedding and replication were detected in most nasal, throat and rectal swabs and nasal turbinates and lungs on 1, 2 and 3 DPI, but not on day 7, respectively. In conclusion, molecular imaging of infected ferrets revealed a progressive consolidation on CT with corresponding [(18)F]-FDG uptake. Strong positive correlations were measured between SUVMax and bronchiolitis-related pathologic scoring (Spearman’s ρ = 0.75). Importantly, the extensive areas of patchy GGO and consolidation seen on CT in the ferret model at 6 DPI are similar to that reported for human H1N1pdm infections. In summary, these first molecular imaging studies of lower respiratory infection with H1N1pdm show that FDG-PET can give insight into the spatiotemporal progression of the inflammation in real-time.",2012 Jul 20,"['Jonsson, Colleen B.', 'Camp, Jeremy V.', 'Wu, Albert', 'Zheng, Huaiyu', 'Kraenzle, Jennifer L.', 'Biller, Ashley E.', 'Vanover, Carol D.', 'Chu, Yong-Kyu', 'Ng, Chin K.', 'Proctor, Mary', 'Sherwood, Leslie', 'Steffen, Marlene C.', 'Mollura, Daniel J.']",PLoS One,,,True
3b1fca9311e0efc4368f3775dd878f57c5978a5e,PMC,The Effects of Simvastatin or Interferon-α on Infectivity of Human Norovirus Using a Gnotobiotic Pig Model for the Study of Antivirals,http://dx.doi.org/10.1371/journal.pone.0041619,PMC3402445,22911825,CC BY,"The lack of an animal model for human norovirus (HuNoV) has hindered the development of therapeutic strategies. This study demonstrated that a commonly used cholesterol-lowering statin medication, simvastatin, which increases HuNoV replication in an in vitro replicon system, also enhances HuNoV infectivity in the gnotobiotic (Gn) pig model. In contrast, oral treatment with interferon (IFN)-α reduces HuNoV infectivity. Young piglets, all with A or H1 histo-blood group antigens on enterocytes, were treated orally with 8 mg/kg/day of simvastatin; 5 days later, the pigs were inoculated orally with a GII.4 HuNoV (HS194/2009/US strain) and then treated with simvastatin for 5 more days. Simvastatin induced significantly earlier onset and longer duration of HuNoV fecal shedding in treated pigs, frequently with higher fecal viral titers. Simvastatin impaired poly (I:C)-induced IFN-α expression in macrophages or dendritic cells, possibly due to lowered toll-like receptor (TLR) 3 expression; however, the mechanisms were not related to interferon regulatory factor 3 or nuclear factor kappa B signaling pathway. Thus, the enhanced, earlier infectivity of HuNoV in simvastatin-treated pigs coincided with the inhibitory effect of simvastatin on innate immunity. In contrast to the increased HuNoV shedding that simvastatin induced, viral shedding during the treatment period was reduced or curtailed in the HuNoV-inoculated pigs pre-treated/treated with human IFN-α. Our findings are the first to indicate that IFN-α has potential as antiviral therapy against HuNoV. Based on these intriguing and novel findings using the Gn pig model, we confirmed that HuNoV infectivity is altered by treatment with simvastatin or IFN-α. Collectively, these findings indicate that Gn pigs are a useful model to test immunomodulators or efficacy of antivirals against HuNoV.",2012 Jul 23,"['Jung, Kwonil', 'Wang, Qiuhong', 'Kim, Yunjeong', 'Scheuer, Kelly', 'Zhang, Zhenwen', 'Shen, Quan', 'Chang, Kyeong-Ok', 'Saif, Linda J.']",PLoS One,,,True
033810c43899f8bbaea3ecb2b86c192c0e020451,PMC,"Acute respiratory infections, influenza-like illness and JIA: impact on disease activity and response to the influenza vaccine",http://dx.doi.org/10.1186/1546-0096-10-S1-A103,PMC3403110,,CC BY,,2012 Jul 13,"['Carvalho, Luciana M', 'Paula, Flávia E', 'Silvestre, Rodrigo VD', 'Roberti, Luciana R', 'Mello, Wyller A', 'Arruda, Eurico', 'Ferriani, Virginia PL']",Pediatr Rheumatol Online J,,,False
16283e25f01d47898ad2b82d56bd81d5ccf44a5d,PMC,Suppression of feline coronavirus replication in vitro by cyclosporin A,http://dx.doi.org/10.1186/1297-9716-43-41,PMC3403912,22546085,CC BY,"The feline infectious peritonitis virus (FIPV) is a member of the feline coronavirus family that causes FIP, which is incurable and fatal in cats. Cyclosporin A (CsA), an immunosuppressive agent that targets the nuclear factor pathway of activated T-cells (NF-AT) to bind cellular cyclophilins (CyP), dose-dependently inhibited FIPV replication in vitro. FK506 (an immunosuppressor of the pathway that binds cellular FK506-binding protein (FKBP) but not CyP) did not affect FIPV replication. Neither cell growth nor viability changed in the presence of either CsA or FK506, and these factors did not affect the NF-AT pathway in fcwf-4 cells. Therefore, CsA does not seem to exert inhibitory effects via the NF-AT pathway. In conclusion, CsA inhibited FIPV replication in vitro and further studies are needed to verify the practical value of CsA as an anti-FIPV treatment in vivo.",2012 Apr 30,"['Tanaka, Yoshikazu', 'Sato, Yuka', 'Osawa, Shuichi', 'Inoue, Mai', 'Tanaka, Satoka', 'Sasaki, Takashi']",Vet Res,,,True
49a40a6447a61f2a4a725095b19ac648419c09f7,PMC,"The Dynamics, Causes and Possible Prevention of Hepatitis E Outbreaks",http://dx.doi.org/10.1371/journal.pone.0041135,PMC3404073,22911752,CC BY,"Rapidly spreading infectious diseases are a serious risk to public health. The dynamics and the factors causing outbreaks of these diseases can be better understood using mathematical models, which are fit to data. Here we investigate the dynamics of a Hepatitis E outbreak in the Kitgum region of northern Uganda during 2007 to 2009. First, we use the data to determine that [Image: see text] is approximately 2.25 for the outbreak. Secondly, we use a model to estimate that the critical level of latrine and bore hole coverages needed to eradicate the epidemic is at least [Image: see text] and [Image: see text] respectively. Lastly, we further investigate the relationship between the co-infection factor for malaria and Hepatitis E on the value of [Image: see text] for Hepatitis E. Taken together, these results provide us with a better understanding of the dynamics and possible causes of Hepatitis E outbreaks.",2012 Jul 24,"['Nannyonga, Betty', 'Sumpter, David J. T.', 'Mugisha, Joseph Y. T.', 'Luboobi, Livingstone S.']",PLoS One,,,True
3fe4e2a98af36485a9a4dc93c30eef62522af0e0,PMC,Cytokine and Chemokine Levels in Patients with Severe Fever with Thrombocytopenia Syndrome Virus,http://dx.doi.org/10.1371/journal.pone.0041365,PMC3404083,22911786,CC BY,"BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV), which can cause hemorrhagic fever–like illness, is a newly discovered bunyavirus in China. The pathogenesis of SFTSV infection is poorly understood. However, it has been suggested that immune mechanisms, including cytokines and chemokines, play an important role in disease pathogenesis. In the present study, we investigated host cytokine and chemokine profiles in serum samples of patients with SFTSV infection from Northeast China and explored a possible correlation between cytokine levels and disease severity. METHODS AND PRINCIPAL FINDINGS: Acute phase serum samples from 40 patients, diagnosed with SFTSV infection were included. Patients were divided into two groups – severe or non-severe – based on disease severity. Levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, interleukin-6, interferon (IFN)-γ, IFN- γ-induced protein (IP)-10 and RANTES were measured in the serum samples with commercial ELISAs. Statistical analysis showed that increases in TNF-α, IP-10 and IFN-γ were associated with disease severity. CONCLUSIONS: We suggest that a cytokine-mediated inflammatory response, characterized by cytokine and chemokine production imbalance, might be in part responsible for the disease progression of patients with SFTSV infection.",2012 Jul 24,"['Deng, Baocheng', 'Zhang, Shujun', 'Geng, Yingzhi', 'Zhang, Yuzhong', 'Wang, Yuncheng', 'Yao, Wenqing', 'Wen, Ying', 'Cui, Wei', 'Zhou, Ying', 'Gu, Qiuhong', 'Wang, Wen', 'Wang, Yu', 'Shao, Zhen', 'Wang, Yanli', 'Li, Chengbo', 'Wang, Donglei', 'Zhao, Yitong', 'Liu, Pei']",PLoS One,,,True
3053729be9dadd6180b0b30ed2048dec12bd0401,PMC,Human Bocaviruses Are Not Significantly Associated with Gastroenteritis: Results of Retesting Archive DNA from a Case Control Study in the UK,http://dx.doi.org/10.1371/journal.pone.0041346,PMC3404102,22848470,CC BY,"Gastroenteritis is a common illness causing considerable morbidity and mortality worldwide. Despite improvements in detection methods, a significant diagnostic gap still remains. Human bocavirus (HBoV)s, which are associated with respiratory infections, have also frequently been detected in stool samples in cases of gastroenteritis, and a tentative association between HBoVs, and in particular type-2 HBoVs, and gastroenteritis has previously been made. The aim of this study was to determine the role of HBoVs in gastroenteritis, using archived DNA samples from the case-control Infectious Intestinal Disease Study (IID). DNA extracted from stool samples from 2,256 cases and 2,124 controls were tested for the presence of HBoV DNA. All samples were screened in a real time PCR pan-HBoV assay, and positive samples were then tested in genotype 1 to 3-specific assays. HBoV was detected in 7.4% but no significantly different prevalence was observed between cases and controls. In the genotype-specific assays 106 of the 324 HBoV-positive samples were genotyped, with HBoV-1 predominantly found in controls whilst HBoV-2 was more frequently associated with cases of gastroenteritis (p<0.01). A significant proportion of HBoV positives could not be typed using the type specific assays, 67% of the total positives, and this was most likely due to low viral loads being present in the samples. However, the distribution of the untyped HBoV strains was no different between cases and controls. In conclusion, HBoVs, including HBoV-2 do not appear to be a significant cause of gastroenteritis in the UK population.",2012 Jul 24,"['Nawaz, Sameena', 'Allen, David J.', 'Aladin, Farah', 'Gallimore, Christopher', 'Iturriza-Gómara, Miren']",PLoS One,,,True
dc45028785e8308de18df3a42fe11fe571da2cdc,PMC,Structural Origins for the Loss of Catalytic Activities of Bifunctional Human LTA4H Revealed through Molecular Dynamics Simulations,http://dx.doi.org/10.1371/journal.pone.0041063,PMC3405069,22848428,CC BY,"Human leukotriene A4 hydrolase (hLTA4H), which is the final and rate-limiting enzyme of arachidonic acid pathway, converts the unstable epoxide LTA4 to a proinflammatory lipid mediator LTB4 through its hydrolase function. The LTA4H is a bi-functional enzyme that also exhibits aminopeptidase activity with a preference over arginyl tripeptides. Various mutations including E271Q, R563A, and K565A have completely or partially abolished both the functions of this enzyme. The crystal structures with these mutations have not shown any structural changes to address the loss of functions. Molecular dynamics simulations of LTA4 and tripeptide complex structures with functional mutations were performed to investigate the structural and conformation changes that scripts the observed differences in catalytic functions. The observed protein-ligand hydrogen bonds and distances between the important catalytic components have correlated well with the experimental results. This study also confirms based on the structural observation that E271 is very important for both the functions as it holds the catalytic metal ion at its location for the catalysis and it also acts as N-terminal recognition residue during peptide binding. The comparison of binding modes of substrates revealed the structural changes explaining the importance of R563 and K565 residues and the required alignment of substrate at the active site. The results of this study provide valuable information to be utilized in designing potent hLTA4H inhibitors as anti-inflammatory agents.",2012 Jul 25,"['Thangapandian, Sundarapandian', 'John, Shalini', 'Lazar, Prettina', 'Choi, Sun', 'Lee, Keun Woo']",PLoS One,,,True
959c580ae16696d820337df5f221ea7869b71d69,PMC,Molecular and Microscopic Analysis of Bacteria and Viruses in Exhaled Breath Collected Using a Simple Impaction and Condensing Method,http://dx.doi.org/10.1371/journal.pone.0041137,PMC3405091,22848436,CC BY,"Exhaled breath condensate (EBC) is increasingly being used as a non-invasive method for disease diagnosis and environmental exposure assessment. By using hydrophobic surface, ice, and droplet scavenging, a simple impaction and condensing based collection method is reported here. Human subjects were recruited to exhale toward the device for 1, 2, 3, and 4 min. The exhaled breath quickly formed into tiny droplets on the hydrophobic surface, which were subsequently scavenged into a 10 µL rolling deionized water droplet. The collected EBC was further analyzed using culturing, DNA stain, Scanning Electron Microscope (SEM), polymerase chain reaction (PCR) and colorimetry (VITEK 2) for bacteria and viruses. Experimental data revealed that bacteria and viruses in EBC can be rapidly collected using the method developed here, with an observed efficiency of 100 µL EBC within 1 min. Culturing, DNA stain, SEM, and qPCR methods all detected high bacterial concentrations up to 7000 CFU/m(3) in exhaled breath, including both viable and dead cells of various types. Sphingomonas paucimobilis and Kocuria variants were found dominant in EBC samples using VITEK 2 system. SEM images revealed that most bacteria in exhaled breath are detected in the size range of 0.5–1.0 µm, which is able to enable them to remain airborne for a longer time, thus presenting a risk for airborne transmission of potential diseases. Using qPCR, influenza A H3N2 viruses were also detected in one EBC sample. Different from other devices restricted solely to condensation, the developed method can be easily achieved both by impaction and condensation in a laboratory and could impact current practice of EBC collection. Nonetheless, the reported work is a proof-of-concept demonstration, and its performance in non-invasive disease diagnosis such as bacterimia and virus infections needs to be further validated including effects of its influencing matrix.",2012 Jul 25,"['Xu, Zhenqiang', 'Shen, Fangxia', 'Li, Xiaoguang', 'Wu, Yan', 'Chen, Qi', 'Jie, Xu', 'Yao, Maosheng']",PLoS One,,,True
9aee0cad00998f83f85e815527be1a7ac00881ee,PMC,Antiviral Activity of Isatis indigotica Extract and Its Derived Indirubin against Japanese Encephalitis Virus,http://dx.doi.org/10.1155/2012/925830,PMC3405817,22911608,CC BY,"Isatis indigotica is widely used in Chinese Traditional Medicine for clinical treatment of virus infection, tumor, and inflammation, yet its antiviral activities remain unclear. This study probed antiviral activity of I. indigotica extract and its marker compounds against Japanese encephalitis virus (JEV). I. indigotica methanol extract, indigo, and indirubin proved less cytotoxic than other components, showing inhibitory effect (concentration-dependent) on JEV replication in vitro. Time-of-addition experiments proved the extract, indigo, and indirubin with potent antiviral effect by pretreatment (before infection) or simultaneous treatment (during infection), but not posttreatment (after entry). Antiviral action of these agents showed correlation with blocking virus attachment and exhibited potent virucidal activity. In particular, indirubin had strong protective ability in a mouse model with lethal JEV challenge. The study could yield anti-JEV agents.",2012 Jul 17,"['Chang, Shu-Jen', 'Chang, Yi-Chih', 'Lu, Kai-Zen', 'Tsou, Yi-Yun', 'Lin, Cheng-Wen']",Evid Based Complement Alternat Med,,,True
842df6edd1fa0ce2684a79447ad591b1093d83f3,PMC,IFN-γ Signaling to Astrocytes Protects from Autoimmune Mediated Neurological Disability,http://dx.doi.org/10.1371/journal.pone.0042088,PMC3407093,22848713,CC BY,"Demyelination and axonal degeneration are determinants of progressive neurological disability in patients with multiple sclerosis (MS). Cells resident within the central nervous system (CNS) are active participants in development, progression and subsequent control of autoimmune disease; however, their individual contributions are not well understood. Astrocytes, the most abundant CNS cell type, are highly sensitive to environmental cues and are implicated in both detrimental and protective outcomes during autoimmune demyelination. Experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice expressing signaling defective dominant-negative interferon gamma (IFN-γ) receptors on astrocytes to determine the influence of inflammation on astrocyte activity. Inhibition of IFN-γ signaling to astrocytes did not influence disease incidence, onset, initial progression of symptoms, blood brain barrier (BBB) integrity or the composition of the acute CNS inflammatory response. Nevertheless, increased demyelination at peak acute disease in the absence of IFN-γ signaling to astrocytes correlated with sustained clinical symptoms. Following peak disease, diminished clinical remission, increased mortality and sustained astrocyte activation within the gray matter demonstrate a critical role of IFN-γ signaling to astrocytes in neuroprotection. Diminished disease remission was associated with escalating demyelination, axonal degeneration and sustained inflammation. The CNS infiltrating leukocyte composition was not altered; however, decreased IL-10 and IL-27 correlated with sustained disease. These data indicate that astrocytes play a critical role in limiting CNS autoimmune disease dependent upon a neuroprotective signaling pathway mediated by engagement of IFN-γ receptors.",2012 Jul 27,"['Hindinger, Claudia', 'Bergmann, Cornelia C.', 'Hinton, David R.', 'Phares, Timothy W.', 'Parra, Gabriel I.', 'Hussain, Shabbir', 'Savarin, Carine', 'Atkinson, Roscoe D.', 'Stohlman, Stephen A.']",PLoS One,,,True
bf0c3f90978f7e4794dfe1dd2d90ddb592fc6549,PMC,Influence of Mabs on PrP(Sc) Formation Using In Vitro and Cell-Free Systems,http://dx.doi.org/10.1371/journal.pone.0041626,PMC3407222,22848548,CC BY,"PrP(Sc) is believed to serve as a template for the conversion of PrP(C) to the abnormal isoform. This process requires contact between the two proteins and implies that there may be critical contact sites that are important for conversion. We hypothesized that antibodies binding to either PrP(c)or PrP(Sc) would hinder or prevent the formation of the PrP(C)–PrP(Sc) complex and thus slow down or prevent the conversion process. Two systems were used to analyze the effect of different antibodies on PrP(Sc) formation: (i) neuroblastoma cells persistently infected with the 22L mouse-adapted scrapie stain, and (ii) protein misfolding cyclic amplification (PMCA), which uses PrP(Sc) as a template or seed, and a series of incubations and sonications, to convert PrP(C) to PrP(Sc). The two systems yielded similar results, in most cases, and demonstrate that PrP-specific monoclonal antibodies (Mabs) vary in their ability to inhibit the PrP(C)–PrP(Sc) conversion process. Based on the numerous and varied Mabs analyzed, the inhibitory effect does not appear to be epitope specific, related to PrP(C) conformation, or to cell membrane localization, but is influenced by the targeted PrP region (amino vs carboxy).",2012 Jul 27,"['Chang, Binggong', 'Petersen, Robert', 'Wisniewski, Thomas', 'Rubenstein, Richard']",PLoS One,,,True
8a2fd6ad99f53bb749e4ccaf50fdd36a14bd4aba,PMC,Photodynamic Inactivation of Mammalian Viruses and Bacteriophages,http://dx.doi.org/10.3390/v4071034,PMC3407894,22852040,CC BY,"Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.",2012 Jun 26,"['Costa, Liliana', 'Faustino, Maria Amparo F.', 'Neves, Maria Graça P. M. S.', 'Cunha, Ângela', 'Almeida, Adelaide']",Viruses,,,True
4b3ddd160ebda77b58843d167709d71a73a3bf4a,PMC,Legume Lectins Inhibit Human Parainfluenza Virus Type 2 Infection by Interfering with the Entr,http://dx.doi.org/10.3390/v4071104,PMC3407897,22852043,CC BY,"Three lectins with different sugar binding specificities were investigated for anti-viral activity against human parainfluenza virus type 2 (hPIV-2). The lectins, concanavalin A (Con A), lens culinaris agglutinin (LCA) and peanut agglutinin (PNA), inhibited cell fusion and hemadsorption induced by hPIV-2. Virus nucleoprotein (NP) gene synthesis was largely inhibited, but fusion (F) and hemagglutinin-neuraminidase (HN) gene syntheses were not. An indirect immunofluorescence study showed that Con A inhibited virus NP, F and HN protein syntheses, but LCA did not completely inhibit them, and that PNA inhibited only NP protein synthesis. Using a recombinant green fluorescence protein-expressing hPIV-2, without matrix protein (rghPIV-2ΔM), it was found that virus entry into the cells was not completely prevented. The lectins considerably reduced the number of viruses released compared with that of virus infected cells. The lectins bound to cell surface within 10 min, and many aggregates were observed at 30 min. Con A and LCA slightly disrupted actin microfilaments and microtubules, but PNA had almost no effect on them. These results indicated that the inhibitory effects of the lectins were caused mainly by the considerable prevention of virus adsorption to the cells by the lectin binding to their receptors.",2012 Jun 29,"['Uematsu, Jun', 'Koyama, Aoi', 'Takano, Sayaka', 'Ura, Yukari', 'Tanemura, Miho', 'Kihira, Sahoko', 'Yamamoto, Hidetaka', 'Kawano, Mitsuo', 'Tsurudome, Masato', 'O’Brien, Myles', 'Komada, Hiroshi']",Viruses,,,True
7ed71c815f2ddd8160be8a574698fe6685fe9dda,PMC,Algal Lectins as Potential HIV Microbicide Candidates,http://dx.doi.org/10.3390/md10071476,PMC3407925,22851920,CC BY,"The development and use of topical microbicides potentially offers an additional strategy to reduce the spread of the Human Immunodeficiency Virus (HIV). Carbohydrate-binding agents (CBAs) that show specificity for high mannose carbohydrates on the surface of the heavily glycosylated envelope of HIV are endowed with potent anti-HIV activity. In fact, a number of algal lectins such as cyanovirin-N, microvirin, microcystis viridis lectin, scytovirin, Oscillatoria agardhii agglutinin and griffithsin are considered as potential microbicide candidates to prevent the sexual transmission of HIV through topical applications. They not only inhibit infection of cells by cell-free virus but they can also efficiently prevent virus transmission from virus-infected cells to uninfected CD4(+) target T-lymphocytes and DC-SIGN-directed capture of HIV-1 and transmission to CD4(+) T lymphocytes. This review focuses on the structural properties and carbohydrate specificity of these algal lectins, their antiviral activity against HIV and several other enveloped viruses, their safety profile and viral resistance patterns.",2012 Jul 10,"['Huskens, Dana', 'Schols, Dominique']",Mar Drugs,,,True
074a37594f93652c9db7cef967b21eaa5b70f731,PMC,Extracellular Vesicles and Their Convergence with Viral Pathways,http://dx.doi.org/10.1155/2012/767694,PMC3410301,22888349,CC BY,"Extracellular vesicles (microvesicles), such as exosomes and shed microvesicles, contain a variety of molecules including proteins, lipids, and nucleic acids. Microvesicles appear mostly to originate from multivesicular bodies or to bud from the plasma membrane. Here, we review the convergence of microvesicle biogenesis and aspects of viral assembly and release pathways. Herpesviruses and retroviruses, amongst others, recruit several elements from the microvesicle biogenesis pathways for functional virus release. In addition, noninfectious pleiotropic virus-like vesicles can be released, containing viral and cellular components. We highlight the heterogeneity of microvesicle function during viral infection, addressing microvesicles that can either block or enhance infection, or cause immune dysregulation through bystander action in the immune system. Finally, endogenous retrovirus and retrotransposon elements deposited in our genomes millions of years ago can be released from cells within microvesicles, suggestive of a viral origin of the microvesicle system or perhaps of an evolutionary conserved system of virus-vesicle codependence. More research is needed to further elucidate the complex function of the various microvesicles produced during viral infection, possibly revealing new therapeutic intervention strategies.",2012 Jul 25,"['Wurdinger, Thomas', 'Gatson, NaTosha N.', 'Balaj, Leonora', 'Kaur, Balveen', 'Breakefield, Xandra O.', 'Pegtel, D. Michiel']",Adv Virol,,,True
b9a8782661a61d1562b8d6a2098fd35c76b35349,PMC,"Origin, diversity, and maturation of human antiviral antibodies analyzed by high-throughput sequencing",http://dx.doi.org/10.3389/fmicb.2012.00277,PMC3410596,22876240,CC BY,"Our understanding of how antibodies are generated and function could help develop effective vaccines and antibody-based therapeutics against viruses such as HIV-1, SARS coronavirus (SARS CoV), and Hendra and Nipah viruses (henipaviruses). Although broadly neutralizing antibodies (bnAbs) against the HIV-1 were observed in patients, elicitation of such bnAbs remains a major challenge when compared to other viral targets. We previously hypothesized that HIV-1 could have evolved a strategy to evade the immune system due to absent or very weak binding of germline antibodies to the conserved epitopes that may not be sufficient to initiate and/or maintain an effective immune response. To further explore our hypothesis, we used the 454 sequence analysis of a large naïve library of human IgM antibodies which had been used for selecting antibodies against SARS CoV receptor-binding domain (RBD), and soluble G proteins (sG) of henipaviruses. We found that the human IgM repertoires from the 454 sequencing have diverse germline usages, recombination patterns, junction diversity, and a lower extent of somatic mutation. In this study, we identified antibody maturation intermediates that are related to bnAbs against the HIV-1 and other viruses as observed in normal individuals, and compared their genetic diversity and somatic mutation level along with available structural and functional data. Further computational analysis will provide framework for understanding the underlying genetic and molecular determinants related to maturation pathways of antiviral bnAbs that could be useful for applying novel approaches to the design of effective vaccine immunogens and antibody-based therapeutics.",2012 Aug 2,"['Prabakaran, Ponraj', 'Zhu, Zhongyu', 'Chen, Weizao', 'Gong, Rui', 'Feng, Yang', 'Streaker, Emily', 'Dimitrov, Dimiter S.']",Front Microbiol,,,True
4e8f8ad6957ffac26673761935854e6c05b7768e,PMC,Structural Bases of Coronavirus Attachment to Host Aminopeptidase N and Its Inhibition by Neutralizing Antibodies,http://dx.doi.org/10.1371/journal.ppat.1002859,PMC3410853,22876187,CC BY,"The coronaviruses (CoVs) are enveloped viruses of animals and humans associated mostly with enteric and respiratory diseases, such as the severe acute respiratory syndrome and 10–20% of all common colds. A subset of CoVs uses the cell surface aminopeptidase N (APN), a membrane-bound metalloprotease, as a cell entry receptor. In these viruses, the envelope spike glycoprotein (S) mediates the attachment of the virus particles to APN and subsequent cell entry, which can be blocked by neutralizing antibodies. Here we describe the crystal structures of the receptor-binding domains (RBDs) of two closely related CoV strains, transmissible gastroenteritis virus (TGEV) and porcine respiratory CoV (PRCV), in complex with their receptor, porcine APN (pAPN), or with a neutralizing antibody. The data provide detailed information on the architecture of the dimeric pAPN ectodomain and its interaction with the CoV S. We show that a protruding receptor-binding edge in the S determines virus-binding specificity for recessed glycan-containing surfaces in the membrane-distal region of the pAPN ectodomain. Comparison of the RBDs of TGEV and PRCV to those of other related CoVs, suggests that the conformation of the S receptor-binding region determines cell entry receptor specificity. Moreover, the receptor-binding edge is a major antigenic determinant in the TGEV envelope S that is targeted by neutralizing antibodies. Our results provide a compelling view on CoV cell entry and immune neutralization, and may aid the design of antivirals or CoV vaccines. APN is also considered a target for cancer therapy and its structure, reported here, could facilitate the development of anti-cancer drugs.",2012 Aug 2,"['Reguera, Juan', 'Santiago, César', 'Mudgal, Gaurav', 'Ordoño, Desiderio', 'Enjuanes, Luis', 'Casasnovas, José M.']",PLoS Pathog,,,True
7be0c55fb0d4bb5983591cdc5366c67d44aa1b4e,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,True
330375e29f69eec6317d4345ed4b50d6553da5e3,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
c6dd496de1c9cadd8d7651bc0b7f4602e493d1c0,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
4d49eed1f9b06bc2de53ac19343bb801847519f1,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
6384cba77fb5c04cba53395d4f066735ec627b50,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
94114dda8bad56f55e93e709f8f5bec01227daf5,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
630c673ca40e5d3d5e7da8e1291e1d1905932602,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
872453c36fd9e95774cca279e4ddbf8d3d42ff8b,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
ccac686a6e523c29bbc10c1902aa9403baf19c7a,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
9400c1add999936c5156c79274d804113841c641,PMC,Host Modulators of H1N1 Cytopathogenicity,http://dx.doi.org/10.1371/journal.pone.0039284,PMC3410888,22876275,CC BY,"Influenza A virus infects 5–20% of the population annually, resulting in ∼35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors.",2012 Aug 2,"['Ward, Samuel E.', 'Kim, Hyun Seok', 'Komurov, Kakajan', 'Mendiratta, Saurabh', 'Tsai, Pei-Ling', 'Schmolke, Mirco', 'Satterly, Neal', 'Manicassamy, Balaji', 'Forst, Christian V.', 'Roth, Michael G.', 'García-Sastre, Adolfo', 'Blazewska, Katarzyna M.', 'McKenna, Charles E.', 'Fontoura, Beatriz M.', 'White, Michael A.']",PLoS One,,,False
d75571144654e55a962409ab789839f59f7e772d,PMC,Canine Hepacivirus NS3 Serine Protease Can Cleave the Human Adaptor Proteins MAVS and TRIF,http://dx.doi.org/10.1371/journal.pone.0042481,PMC3411667,22870331,CC BY,"Canine hepacivirus (CHV) was recently identified in domestic dogs and horses. The finding that CHV is genetically the virus most closely related to hepatitis C virus (HCV) has raised the question of whether HCV might have evolved as the result of close contact between dogs and/or horses and humans. The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF). The proteolytic activity of CHV NS3/4A was evaluated using a bacteriophage lambda genetic screen. Human MAVS- and TRIF-specific cleavage sites were engineered into the lambda cI repressor. Upon infection of Escherichia coli cells coexpressing these repressors and a CHV NS3/4A construct, lambda phage replicated up to 2000-fold more efficiently than in cells expressing a CHV protease variant carrying the inactivating substitution S139A. Comparable results were obtained when several HCV NS3/4A constructs of genotype 1b were assayed. This indicates that CHV can disrupt the human innate antiviral defense signaling pathway and suggests a possible evolutionary relationship between CHV and HCV.",2012 Aug 1,"['Parera, Mariona', 'Martrus, Gloria', 'Franco, Sandra', 'Clotet, Bonaventura', 'Martinez, Miguel Angel']",PLoS One,,,True
8e16bcce21552d6bb63b2407557f0a8dbd8b007e,PMC,High Rates of Detection of Respiratory Viruses in Tonsillar Tissues from Children with Chronic Adenotonsillar Disease,http://dx.doi.org/10.1371/journal.pone.0042136,PMC3411673,22870291,CC BY,"Chronic tonsillar diseases are an important health problem, leading to large numbers of surgical procedures worldwide. Little is known about pathogenesis of these diseases. In order to investigate the role of respiratory viruses in chronic adenotonsillar diseases, we developed a cross-sectional study to determine the rates of viral detections of common respiratory viruses detected by TaqMan real time PCR (qPCR) in nasopharyngeal secretions, tonsillar tissues and peripheral blood from 121 children with chronic tonsillar diseases, without symptoms of acute respiratory infections. At least one respiratory virus was detected in 97.5% of patients. The viral co-infection rate was 69.5%. The most frequently detected viruses were human adenovirus in 47.1%, human enterovirus in 40.5%, human rhinovirus in 38%, human bocavirus in 29.8%, human metapneumovirus in 17.4% and human respiratory syncytial virus in 15.7%. Results of qPCR varied widely between sample sites: human adenovirus, human bocavirus and human enterovirus were predominantly detected in tissues, while human rhinovirus was more frequently detected in secretions. Rates of virus detection were remarkably high in tonsil tissues: over 85% in adenoids and close to 70% in palatine tonsils. In addition, overall virus detection rates were higher in more hypertrophic than in smaller adenoids (p = 0.05), and in the particular case of human enteroviruses, they were detected more frequently (p = 0.05) in larger palatine tonsils than in smaller ones. While persistence/latency of DNA viruses in tonsillar tissues has been documented, such is not the case of RNA viruses. Respiratory viruses are highly prevalent in adenoids and palatine tonsils of patients with chronic tonsillar diseases, and persistence of these viruses in tonsils may stimulate chronic inflammation and play a role in the pathogenesis of these diseases.",2012 Aug 3,"['Proenca-Modena, Jose Luiz', 'Pereira Valera, Fabiana Cardoso', 'Jacob, Marcos Gerhardinger', 'Buzatto, Guilherme Pietrucci', 'Saturno, Tamara Honorato', 'Lopes, Lucia', 'Souza, Jamila Mendonça', 'Paula, Flavia Escremim', 'Silva, Maria Lucia', 'Carenzi, Lucas Rodrigues', 'Tamashiro, Edwin', 'Arruda, Eurico', 'Anselmo-Lima, Wilma Terezinha']",PLoS One,,,True
692088c942db684cd4e1ec03c927eb3ae6f6caf6,PMC,Association of Fcγ Receptor IIB Polymorphism with Cryptococcal Meningitis in HIV-Uninfected Chinese Patients,http://dx.doi.org/10.1371/journal.pone.0042439,PMC3411792,22879986,CC BY,"BACKGROUND: As important regulators of the immune system, the human Fcγ receptors (FcγRs) have been demonstrated to play important roles in the pathogenesis of various infectious diseases. The aim of the present study was to identify the association between FCGR polymorphisms and cryptococcal meningitis. METHODOLOGY/PRINCIPAL FINDINGS: In this case control genetic association study, we genotyped four functional polymorphisms in low-affinity FcγRs, including FCGR2A 131H/R, FCGR3A 158F/V, FCGR3B NA1/NA2, and FCGR2B 232I/T, in 117 patients with cryptococcal meningitis and 190 healthy controls by multiplex SNaPshot technology. Among the 117 patients with cryptococcal meningitis, 59 had predisposing factors. In patients with cryptococcal meningitis, the FCGR2B 232I/I genotype was over-presented (OR = 1.652, 95% CI [1.02–2.67]; P = 0.039) and the FCGR2B 232I/T genotype was under-presented (OR = 0.542, 95% CI [0.33–0.90]; P = 0.016) in comparison with control group. In cryptococcal meningitis patients without predisposing factors, FCGR2B 232I/I genotype was also more frequently detected (OR = 1.958, 95% CI [1.05–3.66]; P = 0.033), and the FCGR2B 232I/T genotype was also less frequently detected (OR = 0.467, 95% CI [0.24–0.91]; P = 0.023) than in controls. No significant difference was found among FCGR2A 131H/R, FCGR3A 158F/V, and FCGR3B NA1/NA2 genotype frequencies between patients and controls. CONCLUSION/SIGNIFICANCE: We found for the first time associations between cryptococcal meningitis and FCGR2B 232I/T genotypes, which suggested that FcγRIIB might play an important role in the central nervous system infection by Cryptococcus in HIV-uninfected individuals.",2012 Aug 3,"['Hu, Xiu-Ping', 'Wu, Ji-Qin', 'Zhu, Li-Ping', 'Wang, Xuan', 'Xu, Bin', 'Wang, Rui-Ying', 'Ou, Xue-Ting', 'Weng, Xin-Hua']",PLoS One,,,True
ca57f284dbad5683f531ee130483ca080a1f2d98,PMC,IL-10 Mediated Regulation of Liver Inflammation during Acute Murine Cytomegalovirus Infection,http://dx.doi.org/10.1371/journal.pone.0042850,PMC3411849,22880122,CC BY,"Various cell types in both lymphoid and non-lymphoid tissues produce the anti-inflammatory cytokine interleukin (IL)-10 during murine cytomegalovirus (MCMV) infection. The functions of IL-10 in the liver during acute infection and the cells that generate this cytokine at this site have not been extensively investigated. In this study, we demonstrate that the production of IL-10 in the liver is elevated in C57BL/6 mice during late acute MCMV infection. Using IL-10 green fluorescence protein (GFP) reporter knock-in mice, designated IL-10-internal ribosomal entry site (IRES)-GFP-enhanced reporter (tiger), NK cells are identified as major IL-10 expressing cells in the liver after infection, along with T cells and other leukocytes. In the absence of IL-10, mice exhibit marked elevations in proinflammatory cytokines and in the numbers of mononuclear cells and lymphocytes infiltrating the liver during this infection. IL-10-deficiency also enhances liver injury without improving viral clearance from this site. Collectively, the results indicate that IL-10-producing cells in the liver provide protection from collateral injury by modulating the inflammatory response associated with MCMV infection.",2012 Aug 3,"['Gaddi, Pamela J.', 'Crane, Meredith J.', 'Kamanaka, Masahito', 'Flavell, Richard A.', 'Yap, George S.', 'Salazar-Mather, Thais P.']",PLoS One,,,True
9009370b71d913612356de26f968966c3399da2d,PMC,Proteomic analysis of purified Newcastle disease virus particles,http://dx.doi.org/10.1186/1477-5956-10-32,PMC3413529,22571704,CC BY,"BACKGROUND: Newcastle disease virus (NDV) is an enveloped RNA virus, bearing severe economic losses to the poultry industry worldwide. Previous virion proteomic studies have shown that enveloped viruses carry multiple host cellular proteins both internally and externally during their life cycle. To address whether it also occurred during NDV infection, we performed a comprehensive proteomic analysis of highly purified NDV La Sota strain particles. RESULTS: In addition to five viral structural proteins, we detected thirty cellular proteins associated with purified NDV La Sota particles. The identified cellular proteins comprised several functional categories, including cytoskeleton proteins, annexins, molecular chaperones, chromatin modifying proteins, enzymes-binding proteins, calcium-binding proteins and signal transduction-associated proteins. Among these, three host proteins have not been previously reported in virions of other virus families, including two signal transduction-associated proteins (syntenin and Ras small GTPase) and one tumor-associated protein (tumor protein D52). The presence of five selected cellular proteins (i.e., β-actin, tubulin, annexin A2, heat shock protein Hsp90 and ezrin) associated with the purified NDV particles was validated by Western blot or immunogold labeling assays. CONCLUSIONS: The current study presented the first standard proteomic profile of NDV. The results demonstrated the incorporation of cellular proteins in NDV particles, which provides valuable information for elucidating viral infection and pathogenesis.",2012 May 9,"['Ren, Xiangpeng', 'Xue, Chunyi', 'Kong, Qingming', 'Zhang, Chengwen', 'Bi, Yingzuo', 'Cao, Yongchang']",Proteome Sci,,,True
9491f89b53c527904943035f8b4a1f997c3609ad,PMC,Elevated levels of vitamin D and deficiency of mannose binding lectin in dengue hemorrhagic fever,http://dx.doi.org/10.1186/1743-422X-9-86,PMC3413536,22559908,CC BY,"BACKGROUND: Altered plasma concentrations of vitamin D and mannose binding lectin (MBL), components of innate immunity, have been shown to be associated with the pathogenesis of viral infections. The objective of the present study was to find out whether plasma concentrations of MBL and vitamin D are different in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). THE RESULTS: The plasma concentrations of vitamin D and MBL were assessed in 48 DF cases, 45 DHF cases and 20 apparently healthy controls using ELISA based methods. Vitamin D concentrations were found to be higher among both DF and DHF cases as compared to healthy controls (P < 0.005 and P < 0.001). Vitamin D concentrations were not different between DF and DHF cases. When the dengue cases were classified into primary and secondary infections, secondary DHF cases had significantly higher concentrations of vitamin D as compared to secondary DF cases (P < 0.050). MBL concentrations were not significantly different between healthy controls and dengue cases. MBL concentrations were observed to be lower in DHF cases as compared to DF cases (P < 0.050). Although MBL levels were not different DF and DHF cases based on immune status, the percentage of primary DHF cases (50%) having MBL levels lower than 500 ng/ml were less compared to primary DF cases (P = 0.038). CONCLUSIONS: The present study suggests that higher concentrations of vitamin D might be associated with secondary DHF while deficiency of MBL may be associated with primary DHF.",2012 May 4,"['Alagarasu, Kalichamy', 'Bachal, Rupali V', 'Bhagat, Asha B', 'Shah, Paresh S', 'Dayaraj, Cecilia']",Virol J,,,True
8a2d2e38286fa86dcf60a8a1b0b95658f2d70850,PMC,"Surveillance of Community Outbreaks of Respiratory Tract Infections Based on House-Call Visits in the Metropolitan Area of Athens, Greece",http://dx.doi.org/10.1371/journal.pone.0040310,PMC3414488,22905091,CC BY,"BACKGROUND: The traditional Serfling-type approach for influenza-like illness surveillance requires long historical time-series. We retrospectively evaluated the use of recent, short, historical time-series for recognizing the onset of community outbreaks of respiratory tract infections (RTIs). METHODS: The data used referred to the proportion of diagnoses for upper or lower RTIs to total diagnoses for house-call visits, performed by a private network of medical specialists (SOS Doctors) in the metropolitan area of Athens, Greece, between January 01, 2000 and October 12, 2008. The reference standard classification of the observations was obtained by generating epidemic thresholds after analyzing the full 9-year period. We evaluated two different alert generating methods [simple regression and cumulative sum (CUSUM), respectively], under a range of input parameters, using data for the previous running 4–6 week period. These methods were applied if the previous weeks contained non-aberrant observations. RESULTS: We found that the CUSUM model with a specific set of parameters performed marginally better than simple regression for both groups. The best results (sensitivity, specificity) for simple regression and CUSUM models for upper RTIs were (1.00, 0.82) and (0.94, 0.93) respectively. Corresponding results for lower RTIs were (1.00, 0.80) and (0.93, 0.91) respectively. CONCLUSIONS: Short-term data for house-call visits can be used rather reliably to identify respiratory tract outbreaks in the community using simple regression and CUSUM methods. Such surveillance models could be particularly useful when a large historical database is either unavailable or inaccurate and, thus, traditional methods are not optimal.",2012 Aug 8,"['Spanos, Alex', 'Theocharis, George', 'Karageorgopoulos, Drosos E.', 'Peppas, George', 'Fouskakis, Dimitris', 'Falagas, Matthew E.']",PLoS One,,,True
965f06d2f9a87b69f59b1656c979e04eaa5d75be,PMC,"Comparison of Temporal and Spatial Dynamics of Seasonal H3N2, Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Virus Infections in Ferrets",http://dx.doi.org/10.1371/journal.pone.0042343,PMC3414522,22905124,CC BY,"Humans may be infected by different influenza A viruses—seasonal, pandemic, and zoonotic—which differ in presentation from mild upper respiratory tract disease to severe and sometimes fatal pneumonia with extra-respiratory spread. Differences in spatial and temporal dynamics of these infections are poorly understood. Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1), and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi), as well as describing clinical signs and hematological parameters. H3N2 infection was restricted to the nose and peaked at 1 dpi. pH1N1 infection also peaked at 1 dpi, but occurred at similar levels throughout the respiratory tract. H5N1 infection occurred predominantly in the alveoli, where it peaked for a longer period, from 1 to 3 dpi. The associated lesions followed the same spatial distribution as virus infection, but their severity peaked between 1 and 6 days later. Neutrophil and monocyte counts in peripheral blood correlated with inflammatory cell influx in the alveoli. Of the different parameters used to measure lower respiratory tract disease, relative lung weight and affected lung tissue allowed the best quantitative distinction between the virus groups. There was extra-respiratory spread to more tissues—including the central nervous system—for H5N1 infection than for pH1N1 infection, and to none for H3N2 infection. This study shows that seasonal, pandemic, and zoonotic influenza viruses differ strongly in the spatial and temporal dynamics of infection in the respiratory tract and extra-respiratory tissues of ferrets.",2012 Aug 8,"['van den Brand, Judith M. A.', 'Stittelaar, Koert J.', 'van Amerongen, Geert', 'Reperant, Leslie', 'de Waal, Leon', 'Osterhaus, Albert D. M. E.', 'Kuiken, Thijs']",PLoS One,,,True
25bdd8095f71bd8c6be54898b437e16896ea3790,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,True
f6b8e6990b4e61f4ad98912a5e7ff3455a29d4fc,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
fa8acd41911709dbc9a9b04880149e7a5150ec10,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
c0b1a91e05ba4ff782360a2afb1f89d61e7c5c47,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
4b0e2a496f34d37b1f28083127273d0b8259a354,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
d0d24fc6d2f8e2d91515881ee713162099aeb747,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
483dbb727c11ddbd2609959ef30c08c5389f3cfb,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
4c102c3cb5e7aed5cb9214d7b2bd00524d839d8f,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
d573d37a7a32303177ee7022b5cf1d3b8af5358a,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
43f8af861c5d5c65564a30bcf9627985eb15a3dc,PMC,Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers,http://dx.doi.org/10.1371/journal.pone.0041751,PMC3415403,22912677,CC BY,"This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.",2012 Aug 9,"['Ray, Sandipan', 'Renu, Durairaj', 'Srivastava, Rajneesh', 'Gollapalli, Kishore', 'Taur, Santosh', 'Jhaveri, Tulip', 'Dhali, Snigdha', 'Chennareddy, Srinivasarao', 'Potla, Ankit', 'Dikshit, Jyoti Bajpai', 'Srikanth, Rapole', 'Gogtay, Nithya', 'Thatte, Urmila', 'Patankar, Swati', 'Srivastava, Sanjeeva']",PLoS One,,,False
656d6bf0f5b0f360d55d5321e0c305eb6a12cbab,PMC,IFN-γ protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils,http://dx.doi.org/10.1186/1742-2094-9-104,PMC3419086,22642802,CC BY,"BACKGROUND: The interplay between IFN-γ, IL-17 and neutrophils during CNS inflammatory disease is complex due to cross-regulatory factors affecting both positive and negative feedback loops. These interactions have hindered the ability to distinguish the relative contributions of neutrophils, Th1 and Th17 cell-derived effector molecules from secondary mediators to tissue damage and morbidity. METHODS: Encephalitis induced by a gliatropic murine coronavirus was used as a model to assess the direct contributions of neutrophils, IFN-γ and IL-17 to virus-induced mortality. CNS inflammatory conditions were selectively manipulated by adoptive transfer of virus-primed wild-type (WT) or IFN-γ deficient (GKO) memory CD4(+) T cells into infected SCID mice, coupled with antibody-mediated neutrophil depletion and cytokine blockade. RESULTS: Transfer of GKO memory CD4(+) T cells into infected SCID mice induced rapid mortality compared to recipients of WT memory CD4(+) T cells, despite similar virus control and demyelination. In contrast to recipients of WT CD4(+) T cells, extensive neutrophil infiltration and IL-17 expression within the CNS in recipients of GKO CD4(+) T cells provided a model to directly assess their contribution(s) to disease. Recipients of WT CD4(+) T cells depleted of IFN-γ did not express IL-17 and were spared from mortality despite abundant CNS neutrophil infiltration, indicating that mortality was not mediated by excessive CNS neutrophil accumulation. By contrast, IL-17 depletion rescued recipients of GKO CD4(+) T cells from rapid mortality without diminishing neutrophils or reducing GM-CSF, associated with pathogenic Th17 cells in CNS autoimmune models. Furthermore, co-transfer of WT and GKO CD4(+) T cells prolonged survival in an IFN-γ dependent manner, although IL-17 transcription was not reduced. CONCLUSIONS: These data demonstrate that IL-17 mediates detrimental clinical consequences in an IFN-γ-deprived environment, independent of extensive neutrophil accumulation or GM-CSF upregulation. The results also suggest that IFN-γ overrides the detrimental IL-17 effector responses via a mechanism downstream of transcriptional regulation.",2012 May 29,"['Savarin, Carine', 'Stohlman, Stephen A', 'Hinton, David R', 'Ransohoff, Richard M', 'Cua, Daniel J', 'Bergmann, Cornelia C']",J Neuroinflammation,,,True
7366b56a55321eebcb1d38074932d23ad4346038,PMC,Novel Virostatic Agents against Bluetongue Virus,http://dx.doi.org/10.1371/journal.pone.0043341,PMC3419696,22905259,CC BY,"Bluetongue virus (BTV), a member in the family Reoviridae, is a re-emerging animal disease infecting cattle and sheep. With its recent outbreaks in Europe, there is a pressing need for efficacious antivirals. We presented here the identification and characterization of a novel virostatic molecule against BTV, an aminothiophenecarboxylic acid derivative named compound 003 (C003). The virostatic efficacy of C003 could be improved via chemical modification, leading to a de novo synthesized compound 052 (C052). The 50% effective concentrations (EC(50)) of C003 and C052 were determined at 1.76±0.73 µM and 0.27±0.12 µM, respectively. The 50% cytotoxicity concentration (CC(50)) of C003 was over 100 µM and the CC(50) of C052 was at 82.69 µM. Accordingly, the 50% selective index (SI(50)) of C003 and C052 against BTV was over 57 and 306, respectively. The inhibitory effect of C003/C052 on BTV-induced apoptosis was also confirmed via the inhibition of caspase-3/-7 activation post BTV infection. C003/C052 could inhibit BTV induced CPE even when added as late as 24 h.p.i., indicating that they might act at late stage of viral life-cycle. C003/C052 could reduce over two-logs of both the progeny virus production and the number of genomic viral RNA copies. Interestingly, both the activation of host autophagy and viral protein expression were inhibited post BTV infection when cells were treated with C003 and C052, suggesting that C003/C052 might act as virostatic agents via inhibiting host autophagy activation. Although further investigations might be needed to pin down the exact mechanism of C003/C052, our finding suggested that these compounds might be potent lead compounds with potential novel mechanism of action against BTV.",2012 Aug 15,"['Gu, Linlin', 'Musiienko, Volodymyr', 'Bai, Zhijun', 'Qin, Aijian', 'Schneller, Stewart W.', 'Li, Qianjun']",PLoS One,,,True
6ab7d80bb6dc14cac7fe9c7d5a6060af434bef0a,PMC,"In young children, persistent wheezing is associated with bronchial bacterial infection: a retrospective analysis",http://dx.doi.org/10.1186/1471-2431-12-83,PMC3420249,22726254,CC BY,"BACKGROUND: Young children with persistent wheezing pose a diagnostic and therapeutical challenge to the pediatrician. We aimed to evaluate bacterial bronchial infection as a possible reason for non response to conventional asthma therapy, and to identify and characterise the predominant pathogens involved. METHODS: We retrospectively analysed microbiological and cytological findings in a selected population of young wheezers with symptoms unresponsive to inhaled corticosteroid (ICS) therapy, who underwent flexible bronchoscopy with bronchoalveolar lavage (BAL). Procedural measures were taken to limit contamination risk and quantitative bacterial culture of BAL fluid (significance cut-off ≥ 10(4) colony-forming units/ml) was used. Modern microbiological methods were used for detection of a wide panel of pathogens and for characterisation of the bacterial isolates. RESULTS: 33 children aged between 4 and 38 months, without structural anomalies of the conductive airways were evaluated. Significant bacterial BAL cultures were found in 48,5 % of patients. Haemophilus influenzae was isolated in 30,3 %, Streptococcus pneumoniae in 12,1 % and Moraxella catarrhalis in 12,1 %. All H. influenzae isolates were non-encapsulated strains and definitely distinguished from non-haemolytic H. haemolyticus. Respiratory viruses were detected in 21,9 % of cases with mixed bacterial-viral infection in 12,1 %. Cytology revealed a marked neutrophilic inflammation. CONCLUSIONS: Bacterial infection of the bronchial tree is common in persistent preschool wheezers and provides a possible explanation for non response to ICS therapy. Non-typeable H. influenzae seems to be the predominant pathogen involved, followed by S. pneumoniae and M. catarrhalis.",2012 Jun 22,"['De Schutter, Iris', 'Dreesman, Alexandra', 'Soetens, Oriane', 'De Waele, Marc', 'Crokaert, Françoise', 'Verhaegen, Jan', 'Piérard, Denis', 'Malfroot, Anne']",BMC Pediatr,,,True
845bf0e6613fbb4dfd669bd913f7ebe6020b2cf4,PMC,Acute Fibrinous and Organizing Pneumonia and Undifferentiated Connective Tissue Disease: A Case Report,http://dx.doi.org/10.1155/2012/549298,PMC3420729,22957292,CC BY,"Acute fibrinous and organizing pneumonia (AFOP), recently described, is a histologic pattern characterized by the presence of fibrin “balls” within alveolar spaces. The term undifferentiated connective tissue disease (UCTD) is used to identify autoimmune systemic diseases that do not fulfill the criteria to be classified as a definitive connective tissue disease. The AFOP has never been reported in association with UCTD. The present reported case is a 39-year-old Caucasian, female with dry cough and progressive dyspnea. Eight months later, she was diagnosed with “organizing pneumonia” based on clinical history and radiologic images. She manifested Raynaud's Phenomenon, sicca syndrome, boot and gloves neuropathic pain, and previous hypothyroidism. Antinuclear antibody, rheumatoid factor, and specific autoantibodies were negative. Salivary gland biopsy and electroneuromyiography were normal. The capillaroscopy showed a “scleroderma” pattern with capillary deletion and ectasia. She experienced clinical and radiologic worsening. Despite being submitted to cyclophosphamide pulse, she developed hemorrhage and then died. Thoracotomy pulmonary specimen showed histological pattern of AFOP. This paper shows a rare association of AFOP with UCTD.",2012 Apr 4,"['Valim, Valéria', 'Rocha, Roberta Hora', 'Couto, Roberta Barcelos', 'Paixão, Thaysa Simões', 'Serrano, Érica Vieira']",Case Rep Rheumatol,,,True
2e5bfe1233f49b63cd653c03a695b24f42adaedd,PMC,Novel Method for Isolation of Murine Clara Cell Secretory Protein-Expressing Cells with Traces of Stemness,http://dx.doi.org/10.1371/journal.pone.0043008,PMC3420884,22916196,CC0,"Clara cells are non-ciliated, secretory bronchiolar epithelial cells that serve to detoxify harmful inhaled substances. Clara cells also function as stem/progenitor cells for repair in the bronchioles. Clara cell secretory protein (CCSP) is specifically expressed in pulmonary Clara cells and is widely used as a Clara cell marker. In addition CCSP promoter is commonly used to direct gene expression into the lung in transgenic models. The discovery of CCSP immunoreactivity in plasma membranes of airway lining cells prompted us to explore the possibility of enriching Clara cells by flow cytometry. We established a novel and simple method for the isolation of CCSP-expressing cell Clara cells using a combination of mechanical and enzymatic dissociation followed by flow cytometry sorting technology. We showed that ∼25% of dissociated cells from whole lung expressed CCSP. In the resulting preparation, up to 98% of cells expressed CCSP. Notably, we found that several common stem cell markers including CD44, CD133, Sca-1 and Sox2 were expressed in CCSP(+) cells. Moreover, CCSP(+) cells were able to form spheroid colonies in vitro with 0.97‰ efficiency. Parallel studies in vivo confirmed that a small population of CCSP(−)expressing cells in mouse airways also demonstrates stem cell-like properties such as label retention and harboring rare bronchioalveolar stem cells (BASCs) in terminal bronchioles (TBs). We conclude that CCSP(+) cells exhibit a number of stem cell-like features including stem cell marker expression, bronchosphere colony formation and self-renewal ability. Clara cell isolation by flow cytometry sorting is a useful method for investigating the function of primary Clara cells in stem cell research and mouse models.",2012 Aug 16,"['Wang, Xiao-Yang', 'Keefe, Kathleen M.', 'Jensen-Taubman, Sandra M.', 'Yang, Danlei', 'Yan, Kai', 'Linnoila, R. Ilona']",PLoS One,,,True
dcde88584805e783b69565364975fc31053b6b4e,PMC,Viral and Atypical Bacterial Etiology of Acute Respiratory Infections in Children under 5 Years Old Living in a Rural Tropical Area of Madagascar,http://dx.doi.org/10.1371/journal.pone.0043666,PMC3422262,22912897,CC BY,"BACKGROUND: In Madagascar, very little is known about the etiology and prevalence of acute respiratory infections (ARIs) in a rural tropical area. Recent data are needed to determine the viral and atypical bacterial etiologies in children with defined clinical manifestations of ARIs. METHODS: During one year, we conducted a prospective study on ARIs in children between 2 to 59 months in the community hospital of Ampasimanjeva, located in the south-east of Madagascar. Respiratory samples were analyzed by multiplex real-time RT-PCR, including 18 viruses and 2 atypical bacteria. The various episodes of ARI were grouped into four clinical manifestations with well-documented diagnosis: “Community Acquired Pneumonia”(CAP, group I), “Other acute lower respiratory infections (Other ALRIs, group II)”, “Upper respiratory tract infections with cough (URTIs with cough, group III)”and “Upper respiratory tract infections without cough (URTIs without cough, group IV)”. RESULTS: 295 children were included in the study between February 2010 and February 2011. Viruses and/or atypical bacteria respiratory pathogens were detected in 74.6% of samples, the rate of co-infection was 27.3%. Human rhinovirus (HRV; 20.5%), metapneumovirus (HMPV A/B, 13.8%), coronaviruses (HCoV, 12.5%), parainfluenza virus (HPIV, 11.8%) and respiratory syncytial virus A and B (RSV A/B, 11.8%) were the most detected. HRV was predominantly single detected (23.8%) in all the clinical groups while HMPV A/B (23.9%) was mainly related to CAP (group I), HPIV (17.3%) to the “Other ALRIs” (group II), RSV A/B (19.5%) predominated in the group “URTIs with cough” (group III) and Adenovirus (HAdV, 17.8%) was mainly detected in the “without cough” (group IV). INTERPRETATION: This study describes for the first time the etiology of respiratory infections in febrile children under 5 years in a malaria rural area of Madagascar and highlights the role of respiratory viruses in a well clinically defined population of ARIs.",2012 Aug 17,"['Hoffmann, Jonathan', 'Rabezanahary, Henintsoa', 'Randriamarotia, Martin', 'Ratsimbasoa, Arsène', 'Najjar, Josette', 'Vernet, Guy', 'Contamin, Bénédicte', 'Paranhos-Baccalà, Gláucia']",PLoS One,,,True
e6dcb411da6446850724d574d0e6bbb507a1f4ba,PMC,Development of Real-Time PCR Array for Simultaneous Detection of Eight Human Blood-Borne Viral Pathogens,http://dx.doi.org/10.1371/journal.pone.0043246,PMC3422334,22912836,CC0,"BACKGROUND: Real-time PCR array for rapid detection of multiple viral pathogens should be highly useful in cases where the sample volume and the time of testing are limited, i.e. in the eligibility testing of tissue and organ donors. FINDINGS: We developed a real-time PCR array capable of simultaneously detecting eight human viral pathogens: human immunodeficiency virus types 1 and 2 (HIV-1 and -2), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus-1 and -2 (HTLV-1 and -2), vaccinia virus (VACV) and West Nile virus (WNV). One hundred twenty (120) primers were designed using a combination of bioinformatics approaches, and, after experimental testing, 24 primer sets targeting eight viral pathogens were selected to set up the array with SYBR Green chemistry. The specificity and sensitivity of the virus-specific primer sets selected for the array were evaluated using analytical panels with known amounts of viruses spiked into human plasma. The array detected: 10 genome equivalents (geq)/ml of HIV-2 and HCV, 50 geq of HIV-1 (subtype B), HBV (genotype A) and WNV. It detected 100–1,000 geq/ml of plasma of HIV-1 subtypes (A – G), group N and CRF (AE and AG) isolates. Further evaluation with a panel consisting of 28 HIV-1 and HIV-2 clinical isolates revealed no cross-reactivity of HIV-1 or HIV-2 specific primers with another type of HIV. All 28 viral isolates were identified with specific primer sets targeting the most conserved genome areas. The PCR array correctly identified viral infections in a panel of 17 previously quantified clinical plasma samples positive for HIV-1, HCV or HBV at as low as several geq per PCR reaction. CONCLUSIONS: The viral array described here demonstrated adequate performance in the testing of donors’ clinical samples. Further improvement in its sensitivity for the broad spectrum of HIV-1 subtypes is under development.",2012 Aug 17,"['Pripuzova, Natalia', 'Wang, Richard', 'Tsai, Shien', 'Li, Bingjie', 'Hung, Guo-Chiuan', 'Ptak, Roger G.', 'Lo, Shyh-Ching']",PLoS One,,,True
db20be21b59adb1bac603a79aeea4154fd703db1,PMC,TcdC Does Not Significantly Repress Toxin Expression in Clostridium difficile 630ΔErm,http://dx.doi.org/10.1371/journal.pone.0043247,PMC3422341,22912837,CC BY,"In the past decade, Clostridium difficile has emerged as an important gut pathogen. Symptoms of C. difficile infection range from mild diarrhea to pseudomembranous colitis, sometimes resulting in colectomy or death. The main virulence factors of C. difficile are toxin A and toxin B. Besides the genes encoding these toxins (tcdA and tcdB), the pathogenicity locus (PaLoc) also contains genes encoding a sigma factor (tcdR) and a putative anti-sigma factor (tcdC). The important role of TcdR as a sigma factor for toxin expression is undisputed, whereas the role of TcdC as an anti-sigma factor, inhibiting toxin expression, is currently the subject of debate. To clarify the role of TcdC in toxin expression, we generated an isogenic ClosTron-based mutant of tcdC in Clostridium difficile strain 630Δ Erm (CT::tcdC) and determined the transcription levels of the PaLoc genes and the expression levels of the toxins in the wild type strain and the tcdC mutant strain. We found only minor differences in transcription levels of the PaLoc genes between the wild type and CT::tcdC strains and total toxin levels did not significantly differ either. These results suggest that in C. difficile 630Δerm TcdC is not a major regulator of toxin expression under the conditions tested.",2012 Aug 17,"['Bakker, Dennis', 'Smits, Wiep Klaas', 'Kuijper, Ed J.', 'Corver, Jeroen']",PLoS One,,,True
9c39ab56559377e3b362be55e8e989e059a01fb0,PMC,Activation of the Canonical Bone Morphogenetic Protein (BMP) Pathway during Lung Morphogenesis and Adult Lung Tissue Repair,http://dx.doi.org/10.1371/journal.pone.0041460,PMC3423416,22916109,CC BY,"Signaling by Bone Morphogenetic Proteins (BMP) has been implicated in early lung development, adult lung homeostasis and tissue-injury repair. However, the precise mechanism of action and the spatio-temporal pattern of BMP-signaling during these processes remains inadequately described. To address this, we have utilized a transgenic line harboring a BMP-responsive eGFP-reporter allele (BRE-eGFP) to construct the first detailed spatiotemporal map of canonical BMP-pathway activation during lung development, homeostasis and adult-lung injury repair. We demonstrate that during the pseudoglandular stage, when branching morphogenesis progresses in the developing lung, canonical BMP-pathway is active mainly in the vascular network and the sub-epithelial smooth muscle layer of the proximal airways. Activation of the BMP-pathway becomes evident in epithelial compartments only after embryonic day (E) 14.5 primarily in cells negative for epithelial-lineage markers, located in the proximal portion of the airway-tree, clusters adjacent to neuro-epithelial-bodies (NEBs) and in a substantial portion of alveolar epithelial cells. The pathway becomes activated in isolated E12.5 mesenchyme-free distal epithelial buds cultured in Matrigel suggesting that absence of reporter activity in these regions stems from a dynamic cross-talk between endoderm and mesenchyme. Epithelial cells with activated BMP-pathway are enriched in progenitors capable of forming colonies in three-dimensional Matrigel cultures. As lung morphogenesis approaches completion, eGFP-expression declines and in adult lung its expression is barely detectable. However, upon tissue-injury, either with naphthalene or bleomycin, the canonical BMP-pathways is re-activated, in bronchial or alveolar epithelial cells respectively, in a manner reminiscent to early lung development and in tissue areas where reparatory progenitor cells reside. Our studies illustrate the dynamic activation of canonical BMP-pathway during lung development and adult lung tissue-repair and highlight its involvement in two important processes, namely, the early development of the pulmonary vasculature and the management of epithelial progenitor pools both during lung development and repair of adult lung tissue-injury.",2012 Aug 20,"['Sountoulidis, Alexandros', 'Stavropoulos, Athanasios', 'Giaglis, Stavros', 'Apostolou, Eirini', 'Monteiro, Rui', 'Chuva de Sousa Lopes, Susana M.', 'Chen, Huaiyong', 'Stripp, Barry R.', 'Mummery, Christine', 'Andreakos, Evangelos', 'Sideras, Paschalis']",PLoS One,,,True
22d812dbf1b71eb834f1244bdd26db698fed6a34,PMC,Co-infection of broilers with Ornithobacterium rhinotracheale and H9N2 avian influenza virus,http://dx.doi.org/10.1186/1746-6148-8-104,PMC3424113,22748160,CC BY,"BACKGROUND: Since 2008, a progressive pneumonia has become prevalent in broilers and laying hens. This disease occurrs the first day after hatching and lasts more than 30 days, resulting in approximately 70% morbidity and 30% mortality in broilers. The objective of this study was to isolate and identify the pathogens that are responsible for the progressive pneumonia and establish an animal model for drug screening. RESULTS: 193 serum samples were collected from 8 intensive farms from 5 provinces in China and analysed in the current research. Our clinical survey showed that 65.2% to 100% of breeding broilers, breeding layers, broilers and laying hens were seropositive for ORT antibodies. From 8 intensive farms, six ORT isolates were identified by PCR and biochemical assays, and two H9N2 viruses were isolated. Newcastle Disease Virus (NDV) and Infectious BronchitisVirus (IBV) were excluded. Typical pneumonia and airsacculitis were observed both in broilers inoculated intraperitoneally with an ORT isolate alone and in those co-infected with ORT and H9N2 virus isolates. Specifically, the survival rate was 30%, 20%, 70%, 50% and 90% in birds inoculated with ORT+H9N2 virus, ORT followed by H9N2 virus, H9N2 virus followed by ORT, and ORT or H9N2 virus alone, respectively. CONCLUSIONS: The results of this study suggest that ORT infections of domestic poultry have been occurring frequently in China. ORT infection can induce higher economic losses and mortality if H9N2 AIV is also present. Although the isolation of ORT and H9N2 virus has been reported previously, there have been no reported co-infections of poultry with these two pathogens. This is the first report of co-infection of broilers with ORT and H9N2 virus, and this co-infection is probably associated with the outbreak of broiler airsacculitis in China, which has caused extensive economic losses.",2012 Jul 2,"['Pan, Qing', 'Liu, Aijing', 'Zhang, Faming', 'Ling, Yong', 'Ou, Changbo', 'Hou, Na', 'He, Cheng']",BMC Vet Res,,,True
4e9aa1aef7efca6b41b1503135145e0dd75a39ce,PMC,Evolution of vertebrate interferon inducible transmembrane proteins,http://dx.doi.org/10.1186/1471-2164-13-155,PMC3424830,22537233,CC BY,"BACKGROUND: Interferon inducible transmembrane proteins (IFITMs) have diverse roles, including the control of cell proliferation, promotion of homotypic cell adhesion, protection against viral infection, promotion of bone matrix maturation and mineralisation, and mediating germ cell development. Most IFITMs have been well characterised in human and mouse but little published data exists for other animals. This study characterised IFITMs in two distantly related marsupial species, the Australian tammar wallaby and the South American grey short-tailed opossum, and analysed the phylogeny of the IFITM family in vertebrates. RESULTS: Five IFITM paralogues were identified in both the tammar and opossum. As in eutherians, most marsupial IFITM genes exist within a cluster, contain two exons and encode proteins with two transmembrane domains. Only two IFITM genes, IFITM5 and IFITM10, have orthologues in both marsupials and eutherians. IFITM5 arose in bony fish and IFITM10 in tetrapods. The bone-specific expression of IFITM5 appears to be restricted to therian mammals, suggesting that its specialised role in bone production is a recent adaptation specific to mammals. IFITM10 is the most highly conserved IFITM, sharing at least 85% amino acid identity between birds, reptiles and mammals and suggesting an important role for this presently uncharacterised protein. CONCLUSIONS: Like eutherians, marsupials also have multiple IFITM genes that exist in a gene cluster. The differing expression patterns for many of the paralogues, together with poor sequence conservation between species, suggests that IFITM genes have acquired many different roles during vertebrate evolution.",2012 Apr 26,"['Hickford, Danielle', 'Frankenberg, Stephen', 'Shaw, Geoff', 'Renfree, Marilyn B']",BMC Genomics,,,True
bc6cf0a4651155d6bbfc135d42d510b900b3d975,PMC,Evolution of vertebrate interferon inducible transmembrane proteins,http://dx.doi.org/10.1186/1471-2164-13-155,PMC3424830,22537233,CC BY,"BACKGROUND: Interferon inducible transmembrane proteins (IFITMs) have diverse roles, including the control of cell proliferation, promotion of homotypic cell adhesion, protection against viral infection, promotion of bone matrix maturation and mineralisation, and mediating germ cell development. Most IFITMs have been well characterised in human and mouse but little published data exists for other animals. This study characterised IFITMs in two distantly related marsupial species, the Australian tammar wallaby and the South American grey short-tailed opossum, and analysed the phylogeny of the IFITM family in vertebrates. RESULTS: Five IFITM paralogues were identified in both the tammar and opossum. As in eutherians, most marsupial IFITM genes exist within a cluster, contain two exons and encode proteins with two transmembrane domains. Only two IFITM genes, IFITM5 and IFITM10, have orthologues in both marsupials and eutherians. IFITM5 arose in bony fish and IFITM10 in tetrapods. The bone-specific expression of IFITM5 appears to be restricted to therian mammals, suggesting that its specialised role in bone production is a recent adaptation specific to mammals. IFITM10 is the most highly conserved IFITM, sharing at least 85% amino acid identity between birds, reptiles and mammals and suggesting an important role for this presently uncharacterised protein. CONCLUSIONS: Like eutherians, marsupials also have multiple IFITM genes that exist in a gene cluster. The differing expression patterns for many of the paralogues, together with poor sequence conservation between species, suggests that IFITM genes have acquired many different roles during vertebrate evolution.",2012 Apr 26,"['Hickford, Danielle', 'Frankenberg, Stephen', 'Shaw, Geoff', 'Renfree, Marilyn B']",BMC Genomics,,,False
1da81f5357aef31dd451b4ed90e7fb255c9af8ee,PMC,Operational efficiency and sustainability of vector control of malaria and dengue: descriptive case studies from the Philippines,http://dx.doi.org/10.1186/1475-2875-11-269,PMC3425236,22873707,CC BY,"BACKGROUND: Analysis is lacking on the management of vector control systems in disease-endemic countries with respect to the efficiency and sustainability of operations. METHODS: Three locations were selected, at the scale of province, municipality and barangay (i.e. village). Data on disease incidence, programme activities, and programme management were collected on-site through meetings and focus group discussions. RESULTS: Adaptation of disease control strategies to the epidemiological situation per barangay, through micro-stratification, brings gains in efficiency, but should be accompanied by further capacity building on local situational analysis for better selection and targeting of vector control interventions within the barangay. An integrated approach to vector control, aiming to improve the rational use of resources, was evident with a multi-disease strategy for detection and response, and by the use of combinations of vector control methods. Collaboration within the health sector was apparent from the involvement of barangay health workers, re-orientation of job descriptions and the creation of a disease surveillance unit. The engagement of barangay leaders and use of existing community structures helped mobilize local resources and voluntary services for vector control. In one location, local authorities and the community were involved in the planning, implementation and evaluation of malaria control, which triggered local programme ownership. CONCLUSIONS: Strategies that contributed to an improved efficiency and sustainability of vector control operations were: micro-stratification, integration of vector control within the health sector, a multi-disease approach, involvement of local authorities, and empowerment of communities. Capacity building on situational analysis and vector surveillance should be addressed through national policy and guidelines.",2012 Aug 8,"['van den Berg, Henk', 'Velayudhan, Raman', 'Ebol, Antonietta', 'Catbagan, Ben HG', 'Turingan, Romulo', 'Tuso, Marisol', 'Hii, Jeffrey']",Malar J,,,True
d92b7e913f313face4f704f326d15fca9a91183d,PMC,Dengue Virus Serotype 2 Blocks Extracellular Signal-Regulated Kinase and Nuclear Factor-κB Activation to Downregulate Cytokine Production,http://dx.doi.org/10.1371/journal.pone.0041635,PMC3425550,22927911,CC BY,"BACKGROUND: Dengue virus (DENV) infection is the most common mosquito-borne viral disease threatening human health around the world. Type I interferon (IFN) and cytokine production are crucial in the innate immune system. We previously reported that DENV serotype 2 (DENV-2) induced low levels of interferon regulatory factor 3 and NF-κB activation, thus leading to reduced production of IFN-β in the early phase of infection. Here, we determined whether DENV infection not only hampers type I IFN activation but also cytokine production triggered by Toll-like receptor (TLR) signaling. METHODOLOGY/PRINCIPAL FINDINGS: We used quantitative RT-PCR and found that only low levels of IFN-β and inflammatory cytokines such as interleukin 10 (IL-10), IL-12 and tumor necrosis factor α (TNFα) mRNA were detected in DENV-2–infected bone-marrow–derived dendritic cells. Furthermore, DENV-2 infection repressed cytokine production triggered by TLR signaling. To elucidate the molecular mechanisms underlying this suppression event, we measured NF-κB activation by p65 nuclear translocation and luciferase reporter assay and found that NF-κB activation triggered by TLR ligands was blocked by DENV-2 infection. As well, extracellular signal-regulated kinase (ERK) activity was suppressed by DENV-2 infection. CONCLUSIONS/SIGNIFICANCE: To downregulate the host innate immunity, DENV-2 by itself is a weak inducer of type I IFN and cytokines, furthermore DENV-2 can also block the TLR-triggered ERK–NF-κB activation and cytokine production.",2012 Aug 22,"['Chang, Tsung-Hsien', 'Chen, Siang-Ru', 'Yu, Chia-Yi', 'Lin, You-Sheng', 'Chen, Yao-Shen', 'Kubota, Toru', 'Matsuoka, Mayumi', 'Lin, Yi-Ling']",PLoS One,,,True
46ad7c3b64488b2ccb6556e31bc12a5ec9e8de0e,PMC,Identification of a Novel Bat Papillomavirus by Metagenomics,http://dx.doi.org/10.1371/journal.pone.0043986,PMC3427170,22937142,CC BY,"The discovery of novel viruses in animals expands our knowledge of viral diversity and potentially emerging zoonoses. High-throughput sequencing (HTS) technology gives millions or even billions of sequence reads per run, allowing a comprehensive survey of the genetic content within a sample without prior nucleic acid amplification. In this study, we screened 156 rectal swab samples from apparently healthy bats (n = 96), pigs (n = 9), cattles (n = 9), stray dogs (n = 11), stray cats (n = 11) and monkeys (n = 20) using a HTS metagenomics approach. The complete genome of a novel papillomavirus (PV), Miniopterus schreibersii papillomavirus type 1 (MscPV1), with L1 of 60% nucleotide identity to Canine papillomavirus (CPV6), was identified in a specimen from a Common Bent-wing Bat (M. schreibersii). It is about 7.5kb in length, with a G+C content of 45.8% and a genomic organization similar to that of other PVs. Despite the higher nucleotide identity between the genomes of MscPV1 and CPV6, maximum-likelihood phylogenetic analysis of the L1 gene sequence showed that MscPV1 and Erethizon dorsatum papillomavirus (EdPV1) are most closely related. Estimated divergence time of MscPV1 from the EdPV1/MscPV1 common ancestor was approximately 60.2–91.9 millions of years ago, inferred under strict clocks using the L1 and E1 genes. The estimates were limited by the lack of reliable calibration points from co-divergence because of possible host shifts. As the nucleotide sequence of this virus only showed limited similarity with that of related animal PVs, the conventional approach of PCR using consensus primers would be unlikely to have detected the novel virus in the sample. Unlike the first bat papillomavirus RaPV1, MscPV1 was found in an asymptomatic bat with no apparent mucosal or skin lesions whereas RaPV1 was detected in the basosquamous carcinoma of a fruit bat Rousettus aegyptiacus. We propose MscPV1 as the first member of the novel Dyolambda-papillomavirus genus.",2012 Aug 24,"['Tse, Herman', 'Tsang, Alan K. L.', 'Tsoi, Hoi-Wah', 'Leung, Andy S. P.', 'Ho, Chi-Chun', 'Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung']",PLoS One,,,True
7d6a014c0edde2117d005f3228d2b494084b5e8f,PMC,Human viruses: discovery and emergence,http://dx.doi.org/10.1098/rstb.2011.0354,PMC3427559,22966141,CC BY,"There are 219 virus species that are known to be able to infect humans. The first of these to be discovered was yellow fever virus in 1901, and three to four new species are still being found every year. Extrapolation of the discovery curve suggests that there is still a substantial pool of undiscovered human virus species, although an apparent slow-down in the rate of discovery of species from different families may indicate bounds to the potential range of diversity. More than two-thirds of human viruses can also infect non-human hosts, mainly mammals, and sometimes birds. Many specialist human viruses also have mammalian or avian origins. Indeed, a substantial proportion of mammalian viruses may be capable of crossing the species barrier into humans, although only around half of these are capable of being transmitted by humans and around half again of transmitting well enough to cause major outbreaks. A few possible predictors of species jumps can be identified, including the use of phylogenetically conserved cell receptors. It seems almost inevitable that new human viruses will continue to emerge, mainly from other mammals and birds, for the foreseeable future. For this reason, an effective global surveillance system for novel viruses is needed.",2012 Oct 19,"['Woolhouse, Mark', 'Scott, Fiona', 'Hudson, Zoe', 'Howey, Richard', 'Chase-Topping, Margo']",Philos Trans R Soc Lond B Biol Sci,,,True
59532e3fbb23c6bca0ad86898cdf50817b38633f,PMC,Bringing together emerging and endemic zoonoses surveillance: shared challenges and a common solution,http://dx.doi.org/10.1098/rstb.2011.0362,PMC3427560,22966142,CC BY,"Early detection of disease outbreaks in human and animal populations is crucial to the effective surveillance of emerging infectious diseases. However, there are marked geographical disparities in capacity for early detection of outbreaks, which limit the effectiveness of global surveillance strategies. Linking surveillance approaches for emerging and neglected endemic zoonoses, with a renewed focus on existing disease problems in developing countries, has the potential to overcome several limitations and to achieve additional health benefits. Poor reporting is a major constraint to the surveillance of both emerging and endemic zoonoses, and several important barriers to reporting can be identified: (i) a lack of tangible benefits when reports are made; (ii) a lack of capacity to enforce regulations; (iii) poor communication among communities, institutions and sectors; and (iv) complexities of the international regulatory environment. Redirecting surveillance efforts to focus on endemic zoonoses in developing countries offers a pragmatic approach that overcomes some of these barriers and provides support in regions where surveillance capacity is currently weakest. In addition, this approach addresses immediate health and development problems, and provides an equitable and sustainable mechanism for building the culture of surveillance and the core capacities that are needed for all zoonotic pathogens, including emerging disease threats.",2012 Oct 19,"['Halliday, Jo', 'Daborn, Chris', 'Auty, Harriet', 'Mtema, Zacharia', 'Lembo, Tiziana', 'Bronsvoort, Barend M. deC.', 'Handel, Ian', 'Knobel, Darryn', 'Hampson, Katie', 'Cleaveland, Sarah']",Philos Trans R Soc Lond B Biol Sci,,,True
57a9bfeac00b440a156ffa1f6ae21aca7152b22c,PMC,A framework for the study of zoonotic disease emergence and its drivers: spillover of bat pathogens as a case study,http://dx.doi.org/10.1098/rstb.2012.0228,PMC3427567,22966143,CC BY,"Many serious emerging zoonotic infections have recently arisen from bats, including Ebola, Marburg, SARS-coronavirus, Hendra, Nipah, and a number of rabies and rabies-related viruses, consistent with the overall observation that wildlife are an important source of emerging zoonoses for the human population. Mechanisms underlying the recognized association between ecosystem health and human health remain poorly understood and responding appropriately to the ecological, social and economic conditions that facilitate disease emergence and transmission represents a substantial societal challenge. In the context of disease emergence from wildlife, wildlife and habitat should be conserved, which in turn will preserve vital ecosystem structure and function, which has broader implications for human wellbeing and environmental sustainability, while simultaneously minimizing the spillover of pathogens from wild animals into human beings. In this review, we propose a novel framework for the holistic and interdisciplinary investigation of zoonotic disease emergence and its drivers, using the spillover of bat pathogens as a case study. This study has been developed to gain a detailed interdisciplinary understanding, and it combines cutting-edge perspectives from both natural and social sciences, linked to policy impacts on public health, land use and conservation.",2012 Oct 19,"['Wood, James L. N.', 'Leach, Melissa', 'Waldman, Linda', 'MacGregor, Hayley', 'Fooks, Anthony R.', 'Jones, Kate E.', 'Restif, Olivier', 'Dechmann, Dina', 'Hayman, David T. S.', 'Baker, Kate S.', 'Peel, Alison J.', 'Kamins, Alexandra O.', 'Fahr, Jakob', 'Ntiamoa-Baidu, Yaa', 'Suu-Ire, Richard', 'Breiman, Robert F.', 'Epstein, Jonathan H.', 'Field, Hume E.', 'Cunningham, Andrew A.']",Philos Trans R Soc Lond B Biol Sci,,,True
65438bb97d2ff9725a706241b92f3be6f695f368,PMC,"High Influenza A Virus Infection Rates in Mallards Bred for Hunting in the Camargue, South of France",http://dx.doi.org/10.1371/journal.pone.0043974,PMC3428329,22952832,CC BY,"During the last decade, the role of wildlife in emerging pathogen transmission to domestic animals has often been pointed out. Conversely, far less attention has been paid to pathogen transmission from domestic animals to wildlife. Here, we focus on the case of game restocking, which implies the release of millions of animals worldwide each year. We conducted a 2-year study in the Camargue (Southern France) to investigate the influence of hand-reared Mallard releases on avian influenza virus dynamics in surrounding wildlife. We sampled Mallards (cloacal swabs) from several game duck facilities in 2009 and 2010 before their release. A very high (99%) infection rate caused by an H10N7 strain was detected in the game bird facility we sampled in 2009. We did not detect this strain in shot ducks we sampled, neither during the 2008/2009 nor the 2009/2010 hunting seasons. In 2010 infection rates ranged from 0 to 24% in hand-reared ducks. The 2009 H10N7 strain was fully sequenced. It results from multiple reassortment events between Eurasian low pathogenic strains. Interestingly, H10N7 strains had previously caused human infections in Egypt and Australia. The H10 and N7 segments we sequenced were clearly distinct from the Australian ones but they belonged to the same large cluster as the Egyptian ones. We did not observe any mutation linked to increased virulence, transmission to mammals, or antiviral resistance in the H10N7 strain we identified. Our results indicate that the potential role of hand-reared Mallards in influenza virus epizootics must be taken into account given the likely risk of viral exchange between game bird facilities and wild habitats, owing to duck rearing conditions. Measures implemented to limit transmission from wildlife to domestic animals as well as measures to control transmission from domestic animals to wild ones need to be equally reinforced.",2012 Aug 27,"['Vittecoq, Marion', 'Grandhomme, Viviane', 'Champagnon, Jocelyn', 'Guillemain, Matthieu', 'Crescenzo-Chaigne, Bernadette', 'Renaud, François', 'Thomas, Frédéric', 'Gauthier-Clerc, Michel', 'van der Werf, Sylvie']",PLoS One,,,True
e178386cc3ca613c695540267c215754c02f2abe,PMC,Structural Basis for the dsRNA Specificity of the Lassa Virus NP Exonuclease,http://dx.doi.org/10.1371/journal.pone.0044211,PMC3429428,22937163,CC BY,"Lassa virus causes hemorrhagic fever characterized by immunosuppression. The nucleoprotein of Lassa virus, termed NP, binds the viral genome. It also has an additional enzymatic activity as an exonuclease that specifically digests double-stranded RNA (dsRNA). dsRNA is a strong signal to the innate immune system of viral infection. Digestion of dsRNA by the NP exonuclease activity appears to cause suppression of innate immune signaling in the infected cell. Although the fold of the NP enzyme is conserved and the active site completely conserved with other exonucleases in its DEDDh family, NP is atypical among exonucleases in its preference for dsRNA and its strict specificity for one substrate. Here, we present the crystal structure of Lassa virus NP in complex with dsRNA. We find that unlike the exonuclease in Klenow fragment, the double-stranded nucleic acid in complex with Lassa NP remains base-paired instead of splitting, and that binding of the paired complementary strand is achieved by “relocation” of a basic loop motif from its typical exonuclease position. Further, we find that just one single glycine that contacts the substrate strand and one single tyrosine that stacks with a base of the complementary, non-substrate strand are responsible for the unique substrate specificity. This work thus provides templates for development of antiviral drugs that would be specific for viral, rather than host exonucleases of similar fold and active site, and illustrates how a very few amino acid changes confer alternate specificity and biological phenotype to an enzyme.",2012 Aug 28,"['Hastie, Kathryn M.', 'King, Liam B.', 'Zandonatti, Michelle A.', 'Saphire, Erica Ollmann']",PLoS One,,,True
9ce08e8f877a798f4ff11d70112b69f92fc2427f,PMC,"Human Parainfluenza Virus-Associated Respiratory Tract Infection among Children and Genetic Analysis of HPIV-3 Strains in Beijing, China",http://dx.doi.org/10.1371/journal.pone.0043893,PMC3429441,22937119,CC BY,"The relevance of human parainfluenza viruses (HPIVs) to the epidemiology of acute respiratory infections (ARI) in China is unclear. From May 2008 to September 2010, 443 nasopharyngeal aspirates (NPAs) from hospitalized pediatric patients (age from 1 to 93 months) in Beijing were collected and screened for HPIVs and other common respiratory viruses by real-time RT-PCR. Sixty-two of 443 samples were positive for HPIVs with 4 positive for HPIV-2 and 58 positive for HPIV-3, indicating that HPIV-3 was the predominant virus present during the study period. A phylogenetic tree based on all the available HN (hemagglutinin-neuraminidase) sequences of HPIV-3 indicated that three distinct clusters (A,B, and C) were circulating with some temporal and regional clustering. Cluster C was further divided into sub-clusters, C1, C2, C3 and C4. HPIV-3 from Beijing isolates belonged to sub-cluster C3, and were grouped with the isolates from two Provinces of China and the neighboring country of Japan. Genetic analysis based on entire HN gene revealed that the HPIV-3 isolates from Beijing were highly similar with 97.2%–100% identity at the nucleotide level and these could be divided into two closely related lineages, C3a and C3b. These findings suggested that there was co-circulation of multiple lineages of HPIV-3 in the Beijing region during the study period. This is the first study to describe the epidemiology and molecular characterization of HPIVs in China.",2012 Aug 28,"['Mao, Naiying', 'Ji, Yixin', 'Xie, Zhengde', 'Wang, Huanhuan', 'Wang, Huiling', 'An, Junjing', 'Zhang, Xinxin', 'Zhang, Yan', 'Zhu, Zhen', 'Cui, Aili', 'Xu, Songtao', 'Shen, Kunling', 'Liu, Chunyan', 'Yang, Weizhong', 'Xu, Wenbo']",PLoS One,,,True
c146ea9fadc16cfc9571f748391f3aa07f5acbd7,PMC,Genetic Variation and Population Differentiation in a Medical Herb Houttuynia cordata in China Revealed by Inter-Simple Sequence Repeats (ISSRs),http://dx.doi.org/10.3390/ijms13078159,PMC3430227,22942696,CC BY,"Houttuynia cordata is an important traditional Chinese herb with unresolved genetics and taxonomy, which lead to potential problems in the conservation and utilization of the resource. Inter-simple sequence repeat (ISSR) markers were used to assess the level and distribution of genetic diversity in 226 individuals from 15 populations of H. cordata in China. ISSR analysis revealed low genetic variations within populations but high genetic differentiations among populations. This genetic structure probably mainly reflects the historical association among populations. Genetic cluster analysis showed that the basal clade is composed of populations from Southwest China, and the other populations have continuous and eastward distributions. The structure of genetic diversity in H. cordata demonstrated that this species might have survived in Southwest China during the glacial age, and subsequently experienced an eastern postglacial expansion. Based on the results of genetic analysis, it was proposed that as many as possible targeted populations for conservation be included.",2012 Jul 2,"['Wei, Lin', 'Wu, Xian-Jin']",Int J Mol Sci,,,True
92e99304d6df52227598a5da5996127ee119f6fa,PMC,Quantitative and Chemical Fingerprint Analysis for the Quality Evaluation of Isatis indigotica based on Ultra-Performance Liquid Chromatography with Photodiode Array Detector Combined with Chemometric Methods,http://dx.doi.org/10.3390/ijms13079035,PMC3430281,22942750,CC BY,"A simple and reliable method of ultra-performance liquid chromatography with photodiode array detector (UPLC-PDA) was developed to control the quality of Radix Isatidis (dried root of Isatis indigotica) for chemical fingerprint analysis and quantitative analysis of eight bioactive constituents, including R,S-goitrin, progoitrin, epiprogoitrin, gluconapin, adenosine, uridine, guanosine, and hypoxanthine. In quantitative analysis, the eight components showed good regression (R > 0.9997) within test ranges, and the recovery method ranged from 99.5% to 103.0%. The UPLC fingerprints of the Radix Isatidis samples were compared by performing chemometric procedures, including similarity analysis, hierarchical clustering analysis, and principal component analysis. The chemometric procedures classified Radix Isatidis and its finished products such that all samples could be successfully grouped according to crude herbs, prepared slices, and adulterant Baphicacanthis cusiae Rhizoma et Radix. The combination of quantitative and chromatographic fingerprint analysis can be used for the quality assessment of Radix Isatidis and its finished products.",2012 Jul 20,"['Shi, Yan-Hong', 'Xie, Zhi-Yong', 'Wang, Rui', 'Huang, Shan-Jun', 'Li, Yi-Ming', 'Wang, Zheng-Tao']",Int J Mol Sci,,,True
79fedd132f61a7c76b5e323cffb2af73caf9687c,PMC,Establishment of a Reverse Genetics System for Studying Human Bocavirus in Human Airway Epithelia,http://dx.doi.org/10.1371/journal.ppat.1002899,PMC3431310,22956907,CC BY,"Human bocavirus 1 (HBoV1) has been identified as one of the etiological agents of wheezing in young children with acute respiratory-tract infections. In this study, we have obtained the sequence of a full-length HBoV1 genome (including both termini) using viral DNA extracted from a nasopharyngeal aspirate of an infected patient, cloned the full-length HBoV1 genome, and demonstrated DNA replication, encapsidation of the ssDNA genome, and release of the HBoV1 virions from human embryonic kidney 293 cells. The HBoV1 virions generated from this cell line-based production system exhibits a typical icosahedral structure of approximately 26 nm in diameter, and is capable of productively infecting polarized primary human airway epithelia (HAE) from the apical surface. Infected HAE showed hallmarks of lung airway-tract injury, including disruption of the tight junction barrier, loss of cilia and epithelial cell hypertrophy. Notably, polarized HAE cultured from an immortalized airway epithelial cell line, CuFi-8 (originally derived from a cystic fibrosis patient), also supported productive infection of HBoV1. Thus, we have established a reverse genetics system and generated the first cell line-based culture system for the study of HBoV1 infection, which will significantly advance the study of HBoV1 replication and pathogenesis.",2012 Aug 30,"['Huang, Qinfeng', 'Deng, Xuefeng', 'Yan, Ziying', 'Cheng, Fang', 'Luo, Yong', 'Shen, Weiran', 'Lei-Butters, Diana C. M.', 'Chen, Aaron Yun', 'Li, Yi', 'Tang, Liang', 'Söderlund-Venermo, Maria', 'Engelhardt, John F.', 'Qiu, Jianming']",PLoS Pathog,,,True
7516383abbd16005d507e7fb5bb6766a8b0f5894,PMC,Goal-Oriented Respiratory Management for Critically Ill Patients with Acute Respiratory Distress Syndrome,http://dx.doi.org/10.1155/2012/952168,PMC3432327,22957224,CC BY,"This paper, based on relevant literature articles and the authors' clinical experience, presents a goal-oriented respiratory management for critically ill patients with acute respiratory distress syndrome (ARDS) that can help improve clinicians' ability to care for these patients. Early recognition of ARDS modified risk factors and avoidance of aggravating factors during hospital stay such as nonprotective mechanical ventilation, multiple blood products transfusions, positive fluid balance, ventilator-associated pneumonia, and gastric aspiration can help decrease its incidence. An early extensive clinical, laboratory, and imaging evaluation of “at risk patients” allows a correct diagnosis of ARDS, assessment of comorbidities, and calculation of prognostic indices, so that a careful treatment can be planned. Rapid administration of antibiotics and resuscitative measures in case of sepsis and septic shock associated with protective ventilatory strategies and early short-term paralysis associated with differential ventilatory techniques (recruitment maneuvers with adequate positive end-expiratory pressure titration, prone position, and new extracorporeal membrane oxygenation techniques) in severe ARDS can help improve its prognosis. Revaluation of ARDS patients on the third day of evolution (Sequential Organ Failure Assessment (SOFA), biomarkers and response to infection therapy) allows changes in the initial treatment plans and can help decrease ARDS mortality.",2012 Aug 23,"['Barbas, Carmen Sílvia Valente', 'Matos, Gustavo Faissol Janot', 'Amato, Marcelo Britto Passos', 'Carvalho, Carlos Roberto Ribeiro']",Crit Care Res Pract,,,True
5a63d131a9fdbdb837c56458c72d6e29942c1fb9,PMC,Cytokine Immunopathogenesis of Enterovirus 71 Brain Stem Encephalitis,http://dx.doi.org/10.1155/2012/876241,PMC3432373,22956971,CC BY,"Enterovirus 71 (EV71) is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS). Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema.",2012 Aug 23,"['Wang, Shih-Min', 'Lei, Huan-Yao', 'Liu, Ching-Chuan']",Clin Dev Immunol,,,True
849541788c0fe480a2fb9e13b20f3937e759b249,PMC,Difficulties in demonstrating long term immunity in FeLV vaccinated cats due to increasing age-related resistance to infection,http://dx.doi.org/10.1186/1746-6148-8-125,PMC3433334,22839692,CC BY,"BACKGROUND: Feline leukaemia virus (FeLV) is a pathogen causing fatal illness in cats worldwide, and as such there is a high demand for products to protect against disease. The duration of immunity provided by an inactivated FeLV vaccine, Versifel FeLV, when administered to cats of the target age was determined. Kittens received two vaccinations when aged 7 to 9 weeks old, and were subsequently challenged up to 36 months later with the FeLV-A Glasgow isolate. RESULTS: In all studies, all of the younger aged control kittens showed persistent FeLV p27 antigenaemia confirming that the challenge virus was severe and efficacious. In contrast, the control cats did not show the required level of persistent antigenaemia, with a maximum of 45% cats affected in the middle duration study and only 10% in the longer study. However, apart from one animal in the short duration study, all of the cats vaccinated with Versifel FeLV were negative for persistent antigenaemia and can be considered treatment successes. CONCLUSION: In conclusion, we have shown that although age-related resistance to infection with a virulent FeLV challenge is evident from as early as 10 months of age, vaccination with Versifel FeLV may aid in the protection of cats from FeLV related disease up to three years after primary vaccination as kittens.",2012 Jul 28,"['Wilson, Stephen', 'Greenslade, Juliet', 'Saunders, Gillian', 'Holcroft, Catherine', 'Bruce, Lynn', 'Scobey, Andy', 'Childers, Tedd', 'Sture, Gordon', 'Thompson, James']",BMC Vet Res,,,True
3fd791accf9347c1e74f871c73b7d19c534059ca,PMC,A seroepidemiologic study of Reston ebolavirus in swine in the Philippines,http://dx.doi.org/10.1186/1746-6148-8-82,PMC3433389,22709971,CC BY,"BACKGROUND: Ebola viruses cause viral hemorrhagic fever in humans and non-human primates and are endemic in Africa. Reston ebolavirus (REBOV) has caused several epizootics in cynomolgus monkeys (Macaca fascicularis) but is not associated with any human disease. In late 2008, REBOV infections were identified in swine for the first time in the Philippines. METHODS: A total of 215 swine sera collected at two REBOV-affected farms in 2008, in Pangasinan and Bulacan, were tested for the presence of REBOV-specific antibodies using multiple serodiagnosis systems. A total of 98 swine sera collected in a non-epizootic region, Tarlac, were also tested to clarify the prevalence of REBOV infection in the general swine population in the Philippines. RESULTS: Some 70 % of swine sera at the affected farms were positive for REBOV antibodies in the multiple serodiagnosis systems. On the other hand, none of the swine sera collected in Tarlac showed positive reactions in any of the diagnosis systems. CONCLUSIONS: The high prevalence of REBOV infection in swine in the affected farms in 2008 suggests that swine is susceptible for REBOV infection. The multiple serological assays used in the study are thought to be useful for future surveillance of REOBV infection in swine in the Philippines.",2012 Jun 18,"['Sayama, Yusuke', 'Demetria, Catalino', 'Saito, Mariko', 'Azul, Rachel R', 'Taniguchi, Satoshi', 'Fukushi, Shuetsu', 'Yoshikawa, Tomoki', 'Iizuka, Itoe', 'Mizutani, Tetsuya', 'Kurane, Ichiro', 'Malbas, Fidelino F', 'Lupisan, Socorro', 'Catbagan, Davinio P', 'Animas, Samuel B', 'Morales, Rieldrin G', 'Lopez, Emelinda L', 'Dazo, Karen Rose C', 'Cruz, Magdalena S', 'Olveda, Remigio', 'Saijo, Masayuki', 'Oshitani, Hitoshi', 'Morikawa, Shigeru']",BMC Vet Res,,,True
99e7ae6647b3aef265d79aa84720e5e5b584118d,PMC,Human Anti-CCR4 Minibody Gene Transfer for the Treatment of Cutaneous T-Cell Lymphoma,http://dx.doi.org/10.1371/journal.pone.0044455,PMC3433438,22973452,CC BY,"BACKGROUND: Although several therapeutic options have become available for patients with Cutaneous T-cell Lymphoma (CTCL), no therapy has been curative. Recent studies have demonstrated that CTCL cells overexpress the CC chemokine receptor 4 (CCR4). METHODOLOGY/PRINCIPAL FINDINGS: In this study, a xenograft model of CTCL was established and a recombinant adeno-associated viral serotype 8 (AAV8) vector expressing a humanized single-chain variable fragment (scFv)-Fc fusion (scFvFc or “minibody”) of anti-CCR4 monoclonal antibody (mAb) h1567 was evaluated for curative treatment. Human CCR4(+) tumor-bearing mice treated once with intravenous infusion of AAV8 virions encoding the h1567 (AAV8-h1567) minibody showed anti-tumor activity in vivo and increased survival. The AAV8-h1567 minibody notably increased the number of tumor-infiltrating Ly-6G(+) FcγRIIIa(CD16A)(+) murine neutrophils in the tumor xenografts over that of AAV8-control minibody treated mice. Furthermore, in CCR4(+) tumor-bearing mice co-treated with AAV8-h1567 minibody and infused with human peripheral blood mononuclear cells (PBMCs), marked tumor infiltration of human CD16A(+) CD56(+) NK cells was observed. The h1567 minibody also induced in vitro ADCC activity through both mouse neutrophils and human NK cells. CONCLUSIONS/SIGNIFICANCE: Overall, our data demonstrate that the in vivo anti-tumor activity of h1567 minibody is mediated, at least in part, through CD16A(+) immune effector cell ADCC mechanisms. These data further demonstrate the utility of the AAV-minibody gene transfer system in the rapid evaluation of candidate anti-tumor mAbs and the potency of h1567 as a potential novel therapy for CTCL.",2012 Sep 4,"['Han, Thomas', 'Abdel-Motal, Ussama M.', 'Chang, De-Kuan', 'Sui, Jianhua', 'Muvaffak, Asli', 'Campbell, James', 'Zhu, Quan', 'Kupper, Thomas S.', 'Marasco, Wayne A.']",PLoS One,,,True
4e86bcd31bd05b5c131e397b7d3a74fe4020bb0b,PMC,The Impact of Infection on Population Health: Results of the Ontario Burden of Infectious Diseases Study,http://dx.doi.org/10.1371/journal.pone.0044103,PMC3433488,22962601,CC BY,"BACKGROUND: Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. METHODOLOGY/PRINCIPAL FINDINGS: We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005–2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. CONCLUSIONS/SIGNIFICANCE: Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.",2012 Sep 4,"['Kwong, Jeffrey C.', 'Ratnasingham, Sujitha', 'Campitelli, Michael A.', 'Daneman, Nick', 'Deeks, Shelley L.', 'Manuel, Douglas G.', 'Allen, Vanessa G.', 'Bayoumi, Ahmed M.', 'Fazil, Aamir', 'Fisman, David N.', 'Gershon, Andrea S.', 'Gournis, Effie', 'Heathcote, E. Jenny', 'Jamieson, Frances B.', 'Jha, Prabhat', 'Khan, Kamran M.', 'Majowicz, Shannon E.', 'Mazzulli, Tony', 'McGeer, Allison J.', 'Muller, Matthew P.', 'Raut, Abhishek', 'Rea, Elizabeth', 'Remis, Robert S.', 'Shahin, Rita', 'Wright, Alissa J.', 'Zagorski, Brandon', 'Crowcroft, Natasha S.']",PLoS One,,,True
255e2bd7406726ccde903239d96011c340330634,PMC,"Detection of porcine circovirus genotypes 2a and 2b in aborted foetuses from infected swine herds in the State of São Paulo, Brazil",http://dx.doi.org/10.1186/1751-0147-54-29,PMC3434114,22554105,CC BY,"BACKGROUND: Porcine circovirus type 2 (PCV2) has been associated with several disease complexes, including reproductive failure. The aim of this study was to identify the subtypes of PCV2 that are associated with reproductive failure in pigs from the State of São Paulo, Brazil and to investigate co-infections with other infectious organisms. FINDINGS: Samples of 168 aborted foetuses or mummified foetuses from five farrow-to-finish swine farms known to be infected with PCV2 and located in the State of São Paulo were tested for PCV2 by polymerase chain reaction (PCR). Positive samples were additionally tested for porcine parvovirus (PPV), Leptospira spp. and Brucella spp. by PCR. PCV2 was detected in 18 of the samples (10.7%). PPV, Brucella spp. and Leptospira spp were found in 2, 10 and 0 cases, respectively. Eleven PCV2 strains were sequenced and determined to be either genotype 2a (n = 1) or 2b (n = 10). CONCLUSIONS: The findings indicate that the frequency of PCV2 infections in aborted porcine foetuses from the State of São Paulo is rather low (10.7%) and that co-infection with other pathogens is common and may be involved in PCV2 associated reproductive failure. No repeatable, characteristic amino acid motifs for regions of the PCV2 capsid protein seemed to be associated with abortion in sows.",2012 May 3,"['de Castro, Alessandra MMG', 'Cruz, Taís F', 'Salgado, Vanessa R', 'Kanashiro, Tatiana M', 'Ferrari, Karen L', 'Araujo, João P', 'Brandão, Paulo E', 'Richtzenhain, Leonardo J']",Acta Vet Scand,,,True
bf0e3ed6e8fa4adbfacbf76e9fa2f5aa1ccdef19,PMC,The VNTR Polymorphism of the DC-SIGNR Gene and Susceptibility to HIV-1 Infection: A Meta-Analysis,http://dx.doi.org/10.1371/journal.pone.0042972,PMC3434151,22957026,CC BY,"BACKGROUND: Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin related (DC-SIGNR) can bind to the human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein and is thus important for the host-pathogen interaction in HIV-1 infection. Studies of the association between the variable number tandem repeat (VNTR) polymorphism of the DC-SIGNR gene and HIV-1 susceptibility have produced controversial results. METHODS AND FINDINGS: We conducted a meta-analysis of the data contained in the literature to clarify these findings. In total, 10 studies consisting of 2683 HIV-1 patients and 3263 controls (2130 healthy controls and 1133 HIV-1 exposed but seronegative (HESN) controls) were included. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were assessed in the main analyses. Further stratified analyses by ethnicity and sample size were performed. By dividing the controls into two groups, healthy controls and HIV-1 exposed but seronegative (HESN) controls, we explored different genetic models to detect any association between the VNTR polymorphism and predisposition to HIV-1 infection. The results showed that the 5-repeat allele carriers (OR = 0.84, 95% CI = 0.73–0.96) and the 5/5 homozygous (OR = 0.68, 95% CI = 0.50–0.93) had significantly reduced risk when using the HIV-1 exposed but seronegative (HESN) as controls. The stratified analyses by ethnicity and sample size confirmed these findings. However, a low to moderate degree of heterogeneity was also found across studies. CONCLUSIONS: Our findings demonstrate that the VNTR polymorphism of the DC-SIGNR gene is associated with a moderate effect on host susceptibility to HIV-1 infection. Similar to the 32-bp deletion in the chemokine receptor-5 gene (CCR5Δ32), the DC-SIGNR VNTR 5-repeat allele might have a role in resistance to HIV infection, particularly in Asian populations.",2012 Sep 5,"['Li, Hui', 'Yu, Xiao-Min', 'Wang, Jia-Xin', 'Hong, Ze-Hui', 'Tang, Nelson Leung-Sang']",PLoS One,,,True
8c701ddbdb052d08eabd99191bd51916a2656ef4,PMC,Self-Reported Use of Personal Protective Equipment among Chinese Critical Care Clinicians during 2009 H1N1 Influenza Pandemic,http://dx.doi.org/10.1371/journal.pone.0044723,PMC3434157,22957101,CC BY,"BACKGROUND: Critically ill patients with 2009 H1N1 influenza are often treated in intensive care units (ICUs), representing significant risk of nosocomial transmission to critical care clinicians and other patients. Despite a large body of literature and guidelines recommending infection control practices, numerous barriers have been identified in ICUs, leading to poor compliance to the use of personal protective equipment (PPE). The use of PPE among critical care clinicians has not been extensively evaluated, especially during the pandemic influenza. This study examined the knowledge, attitudes, and self-reported behaviors, and barriers to compliance with the use of PPE among ICU healthcare workers (HCWs) during the pandemic influenza. METHODOLOGY/PRINCIPAL FINDINGS: A survey instrument consisting of 36 questions was developed and mailed to all HCWs in 21 ICUs in 17 provinces in China. A total of 733 physicians, nurses, and other professionals were surveyed, and 650 (88.7%) were included in the analysis. Fifty-six percent of respondents reported having received training program of pandemic influenza before they cared for H1N1 patients, while 77% reported to have adequate knowledge of self and patient protection. Only 18% of respondents were able to correctly identify all components of PPE, and 55% reported high compliance (>80%) with PPE use during patient care. In multivariate analysis, vaccination for 2009 H1N1 influenza, positive attitudes towards PPE use, organizational factors such as availability of PPE in ICU, and patient information of influenza precautions, as well as reprimand for noncompliance by the supervisors were associated with high compliance, whereas negative attitudes towards PPE use and violation of PPE use were independent predictors of low compliance. CONCLUSION/SIGNIFICANCE: Knowledge and self-reported compliance to recommended PPE use among Chinese critical care clinicians is suboptimal. The perceived barriers should be addressed in order to close the significant gap between perception and knowledge or behavior.",2012 Sep 5,"['Hu, Xiaoyun', 'Zhang, Zhidan', 'Li, Na', 'Liu, Dexin', 'Zhang, Li', 'He, Wei', 'Zhang, Wei', 'Li, Yuexia', 'Zhu, Cheng', 'Zhu, Guijun', 'Zhang, Lipeng', 'Xu, Fang', 'Wang, Shouhong', 'Cao, Xiangyuan', 'Zhao, Huiying', 'Li, Qian', 'Zhang, Xijing', 'Lin, Jiandong', 'Zhao, Shuangping', 'Li, Chen', 'Du, Bin', None]",PLoS One,,,True
cecee9224f871415878f3787539095673d50ca8a,PMC,Ifitm3 Limits the Severity of Acute Influenza in Mice,http://dx.doi.org/10.1371/journal.ppat.1002909,PMC3435252,22969429,CC BY,"Interferon-induced transmembrane (IFITM) proteins are a family of viral restriction factors that inhibit the entry processes of several pathogenic viruses, including influenza A virus (IAV), in vitro. Here we report that IAV-infected knockout mice lacking the Ifitm locus on chromosome 7 exhibited accelerated disease progression, greater mortality, and higher pulmonary and systemic viral burdens as compared to wild type controls. We further observed that the phenotype of Ifitm3-specific knockout mice was indistinguishable from that of mice lacking the entire Ifitm locus. Ifitm3 was expressed by IAV target cells including alveolar type II pneumocytes and tracheal/bronchial respiratory epithelial cells. Robust Ifitm3 expression was also observed in several tissues in the absence of infection. Among murine Ifitm promoters, only that of Ifitm3 could be induced by type I and II interferons. Ifitm3 could also be upregulated by the gp130 cytokines IL-6 and oncostatin M on cells expressing appropriate receptors, suggesting that multiple cytokine signals could contribute to Ifitm3 expression in a cell or tissue-specific manner. Collectively, these findings establish a central role for Ifitm3 in limiting acute influenza in vivo, and provide further insight into Ifitm3 expression and regulation.",2012 Sep 6,"['Bailey, Charles C.', 'Huang, I-Chueh', 'Kam, Christina', 'Farzan, Michael']",PLoS Pathog,,,True
2c3faeb0d5d8690917ef67e2f36bb59a93072c7b,PMC,Toll-like receptors are critical for clearance of Brucella and play different roles in development of adaptive immunity following aerosol challenge in mice,http://dx.doi.org/10.3389/fcimb.2012.00115,PMC3435510,22973560,CC BY,"Brucella spp. cause undulant fever in humans and brucellosis in variety of other animals. Both innate and adaptive immunity have been shown to be important in controlling Brucella infection. Toll-like receptors (TLRs) represent a group of pattern recognition receptors (PRRs) that play critical roles in the host innate immune response, as well as development of adaptive immunity. In the current report, we investigated the role of TLR signaling in the clearance of Brucella and development of adaptive immunity in TLR2(−/−), TLR4(−/−), or MyD88(−/−) mice following aerosol exposure to B. melitensis 16 M. Consistent with previous reports, MyD88 is required for efficient clearance of Brucella from all three organs (lung, spleen, and liver). The results reveal Th2-skewed immune responses in TLR2(−/−) mice late in infection and support a TLR2 requirement for efficient clearance of Brucella from the lungs, but not from the spleen or liver. Similarly, TLR4 is required for efficient clearance of Brucella from the lung, but exhibits a minor contribution to clearance from the spleen and no demonstrable contribution to clearance from the liver. Lymphocyte proliferation assays suggest that the TLRs are not involved in the development of cell-mediated memory response to Brucella antigen. Antibody detection reveals that TLR2 and 4 are required to generate early antigen-specific IgG, but not during the late stages of infection. TLR2 and 4 are only transiently required for IgM production and not at all for IgA production. In contrast, MyD88 is essential for antigen specific IgG production late in infection, but is not required for IgM generation over the course of infection. Surprisingly, despite the prominent role for MyD88 in clearance from all tissues, MyD88-knockout mice express significantly higher levels of serum IgA. These results confirm the important role of MyD88 in controlling infection in the spleen while providing evidence of a prominent contribution to protection in other tissues. In addition, although TLR4 and TLR2 contribute little to control of spleen infection, a significant contribution to clearance of lung infection is described.",2012 Sep 7,"['Pei, Jianwu', 'Ding, Xicheng', 'Fan, Yaping', 'Rice-Ficht, Allison', 'Ficht, Thomas A.']",Front Cell Infect Microbiol,,,True
6a1b5c9d6a0e52a6e0c3bdf192b5acb5bc9fed40,PMC,Diagnostic Devices for Isothermal Nucleic Acid Amplification,http://dx.doi.org/10.3390/s120608319,PMC3436031,22969402,CC BY,"Since the development of the polymerase chain reaction (PCR) technique, genomic information has been retrievable from lesser amounts of DNA than previously possible. PCR-based amplifications require high-precision instruments to perform temperature cycling reactions; further, they are cumbersome for routine clinical use. However, the use of isothermal approaches can eliminate many complications associated with thermocycling. The application of diagnostic devices for isothermal DNA amplification has recently been studied extensively. In this paper, we describe the basic concepts of several isothermal amplification approaches and review recent progress in diagnostic device development.",2012 Jun 14,"['Chang, Chia-Chen', 'Chen, Chien-Cheng', 'Wei, Shih-Chung', 'Lu, Hui-Hsin', 'Liang, Yang-Hung', 'Lin, Chii-Wann']",Sensors (Basel),,,True
45670b1f604c315c742a23956615cd8ef7745f3a,PMC,Impact of a hospital-wide hand hygiene promotion strategy on healthcare-associated infections,http://dx.doi.org/10.1186/2047-2994-1-13,PMC3436662,22958911,CC BY,"BACKGROUND: During the Severe Acute Respiratory Syndrome (SARS) outbreak, high compliance in healthcare workers to hand hygiene was primarily driven by fear. However, the post-SARS period confirmed that this practice was not sustainable. At the Singapore General Hospital, a 1,600-bedded acute tertiary care hospital, the hand hygiene program was revised in early 2007 following Singapore's signing of the pledge to the World Health Organization (WHO) ""Clean Care is Safer Care"" program. FINDINGS: A multi-prong approach was used in designing the hand hygiene program. This included system change; training and education; evaluation and feedback; reminders in the workplace; and institutional safety climate. Hand hygiene compliance rate improved from 20% (in January 2007) to 61% (2010). Improvement was also seen annually in the compliance to each of the 5 moments as well as in all staff categories. Healthcare-associated MRSA infections were reduced from 0.6 (2007) to 0.3 (2010) per 1000 patient-days. CONCLUSIONS: Leadership's support of the program evidenced through visible leadership presence, messaging and release of resources is the key factor in helping to make the program a true success. The hospital was recognised as a Global Hand Hygiene Expert Centre in January 2011. The WHO multi-prong interventions work in improving compliance and reducing healthcare associated infections.",2012 Mar 23,"['Ling, Moi Lin', 'How, Kue Bien']",Antimicrob Resist Infect Control,,,True
ac6a39a0545f0b00b01c5e6875632f9c0f8883f9,PMC,Establishment and reinforcement of the national reference centers for human microbiology in Belgium,http://dx.doi.org/10.1186/0778-7367-70-16,PMC3436681,22958353,CC BY,"BACKGROUND: Microbiology reference laboratories are critical in the development of high-quality clinical and public health services. In Belgium, the reference laboratories performed their activities on a voluntary basis and lacked a legal status. METHODS: Pathogens or groups of pathogens necessitating a national reference center (NRC) were prioritized based on diagnostic and epidemiologic relevance. Terms of reference for each of these pathogens were developed. RESULTS: Recently, 40 NRCs for different pathogens or groups of pathogens have been installed in Belgium to fulfill the following core functions: offering reference diagnostics, collecting reference materials, sharing information and scientific advice, participating in national and international networks, collaborating with research workgroups, and contributing to surveillance activities. CONCLUSIONS: These NRCs are important focal points of the national and international network in public health microbiology.",2012 Jun 22,"['Muyldermans, Gaëtan', 'Litzroth, Amber', 'Ducoffre, Geneviève', 'Quoilin, Sophie', None]",Arch Public Health,,,True
0ed0bedd5005e893440208e3a176694c21e29db3,PMC,"High Incidence of Multiple Viral Infections Identified in Upper Respiratory Tract Infected Children under Three Years of Age in Shanghai, China",http://dx.doi.org/10.1371/journal.pone.0044568,PMC3436764,22970251,CC BY,"BACKGROUND: Upper respiratory tract infection (URTI) is a major reason for hospitalization in childhood. More than 80% of URTIs are viral. Etiological diagnosis of URTIs is important to make correct clinical decisions on treatment methods. However, data for viral spectrum of URTIs are very limited in Shanghai children. METHODS: Nasopharyngeal swabs were collected from a group of 164 children aged below 3 years who were hospitalized due to acute respiratory infection from May 2009 to July 2010 in Shanghai. A VRDAL multiplex PCR for 10 common respiratory viruses was performed on collected specimens compared with the Seeplex® RV15 ACE Detection kit for 15 respiratory viruses. RESULTS: Viruses were detected in 84 (51.2%) patients by VRDAL multiplex PCR, and 8 (4.9%) of cases were mixed infections. Using the Seeplex® RV15 ACE Detection kit, viruses were detected in 129 (78.7%) patients, 49 (29.9%) were co-infected cases. Identified viruses included 37 of human rhinovirus (22.6% of cases), 32 of influenza A virus (19.5%), 30 of parainfluenzavirus-2 (18.3%), 23 of parainfluenzavirus-3 (14.0%), 15 of human enterovirus (9.1%), 14 each of parainfluenzavirus-1, respiratory syncytial virus B and adenovirus (8.5%), 8 of coronavirus 229E/NL63 (4.9%), 6 of human bocavirus (3.7%), 5 each of influenza B virus and respiratory syncytial virus A (3.0%), 3 of parainfluenzavirus-4 (1.8%), 2 of coronavirus OC43/HKU1 (1.2%), and 1 human metapneumovirus (0.6%). CONCLUSIONS: A high frequency of respiratory infections (78.7%) and co-infections (29.9%) was detected in children with acute respiratory infection symptoms in Shanghai. The Seeplex® RV15 ACE detection method was found to be a more reliable high throughput tool than VRDAL method to simultaneously detect multiple respiratory viruses.",2012 Sep 7,"['Zhang, Guocui', 'Hu, Yunwen', 'Wang, Hongping', 'Zhang, Lu', 'Bao, Yixi', 'Zhou, Xiaoming']",PLoS One,,,True
80637e7403f730cb2e22a4af53fade48a1e42a87,PMC,The highly conserved 5' untranslated region as an effective target towards the inhibition of Enterovirus 71 replication by unmodified and appropriate 2'-modified siRNAs,http://dx.doi.org/10.1186/1423-0127-19-73,PMC3438048,22889374,CC BY,"BACKGROUND: Enterovirus 71 (EV71) is a highly infectious agent that plays an etiological role in hand, foot, and mouth disease. It is associated with severe neurological complications and has caused significant mortalities in recent large-scale outbreaks. Currently, no effective vaccine or specific clinical therapy is available against EV71. METHODS: Unmodified 21 nucleotide small interfering RNAs (siRNAs) and classic 2(′)-modified (2(′)-O-methylation or 2(′)-fluoro modification) siRNAs were designed to target highly conserved 5(′) untranslated region (UTR) of the EV71 genome and employed as anti-EV71 agents. Real-time TaqMan RT-PCR, western blot analysis and plaque assays were carried out to evaluate specific viral inhibition by the siRNAs. RESULTS: Transfection of rhabdomyosarcoma (RD) cells with siRNAs targeting the EV71 genomic 5(′) UTR significantly delayed and alleviated the cytopathic effects of EV71 infection, increased cell viability in EV71-infected RD cells. The inhibitory effect on EV71 replication was sequence-specific and dosage-dependent, with significant corresponding decreases in viral RNA, VP1 protein and viral titer. Appropriate 2(′)-modified siRNAs exhibited similar RNA interference (RNAi) activity with dramatically increased serum stability in comparison with unmodified counterparts. CONCLUSION: Sequences were identified within the highly conserved 5(′) UTR that can be targeted to effectively inhibit EV71 replication through RNAi strategies. Appropriate 2(′)-modified siRNAs provide a promising approach to optimizing siRNAs to overcome barriers on RNAi-based antiviral therapies for broader administration.",2012 Aug 13,"['Deng, Jun-Xia', 'Nie, Xiao-Jing', 'Lei, Ying-Feng', 'Ma, Chao-Feng', 'Xu, Dong-Liang', 'Li, Biao', 'Xu, Zhi-Kai', 'Zhang, Guo-Cheng']",J Biomed Sci,,,True
b27d654e2342664a7dc5ea9442bde90b11b0cefd,PMC,An evaluation of the inhibitory effects against rotavirus infection of edible plant extracts,http://dx.doi.org/10.1186/1743-422X-9-137,PMC3439294,22834653,CC BY,"BACKGROUND: Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The developments of specific, potent and accessible antiviral treatments that restrain rotavirus infection remain important to control rotavirus disease. METHODS: 150 plant extracts with nutritional applications were screened in vitro on MA-104 cells for their antiviral activity against rhesus rotavirus (RRV). One extract (Aspalathus linearis (Burm.f.) R.Dahlgren) was also tested for its effect on the loss of transepithelial resistance (TER) of Caco-2 cells caused by simian rotavirus (SA-11) infection. RESULTS: Aqueous extracts of Nelumbo nucifera Gaertn. fruit, Urtica dioica L. root, Aspalathus linearis (Burm.f.) R.Dahlgren leaves, Glycyrrhiza glabra L. root and Olea europaea L. leaves were found to have strong significant antiviral activity with a 50% inhibitory concentration (IC50) < 300 μg/ml. The pure compound 18ß-glycyrrhetinic acid from Glycyrrhiza glabra was found to have the strongest antiviral activity (IC50 46 μM), followed by luteolin and vitexin from Aspalathus linearis (IC50 respectively 116 μM and 129 μM) and apigenin-7-O-glucoside from Melissa officinalis (IC50 150 μM). A combination of Glycyrrhiza glabra L. + Nelumbo nucifera Gaertn. and Urtica dioica L. + Nelumbo nucifera Gaertn. showed synergy in their anti-viral activities. Aspalathus linearis (Burm.f.) R.Dahlgren showed no positive effect on the maintenance of the TER. CONCLUSIONS: These results indicate that nutritional intervention with extracts of Nelumbo nucifera Gaertn., Aspalathus linearis (Burm.f.) R.Dahlgren, Urtica dioica L., Glycyrrhiza glabra L. and Olea europaea L. might be useful in the treatment of diarrhea caused by rotavirus infection.",2012 Jul 26,"['Knipping, Karen', 'Garssen, Johan', 'van’t Land, Belinda']",Virol J,,,True
5759e5ac8b1cc3c13ba04aded6e588a059ad92a0,PMC,Aerosolized avian influenza virus by laboratory manipulations,http://dx.doi.org/10.1186/1743-422X-9-146,PMC3439333,22866888,CC BY,"BACKGROUND: Avian H5N1 influenza viruses present a challenge in the laboratory environment, as they are difficult to collect from the air due to their small size and relatively low concentration. In an effort to generate effective methods of H5N1 air removal and ensure the safety of laboratory personnel, this study was designed to investigate the characteristics of aerosolized H5N1 produced by laboratory manipulations during research studies. RESULTS: Normal laboratory procedures used to process the influenza virus were carried out independently and the amount of virus polluting the on-site atmosphere was measured. In particular, zootomy, grinding, centrifugation, pipetting, magnetic stirring, egg inoculation, and experimental zoogenetic infection were performed. In addition, common accidents associated with each process were simulated, including breaking glass containers, syringe injection of influenza virus solution, and rupturing of centrifuge tubes. A micro-cluster sampling ambient air pollution collection device was used to collect air samples. The collected viruses were tested for activity by measuring their ability to induce hemagglutination with chicken red blood cells and to propagate in chicken embryos after direct inoculation, the latter being detected by reverse-transcription PCR and HA test. The results showed that the air samples from the normal centrifugal group and the negative-control group were negative, while all other groups were positive for H5N1. CONCLUSIONS: Our findings suggest that there are numerous sources of aerosols in laboratory operations involving H5N1. Thus, laboratory personnel should be aware of the exposure risk that accompanies routine procedures involved in H5N1 processing and take proactive measures to prevent accidental infection and decrease the risk of virus aerosol leakage beyond the laboratory.",2012 Aug 6,"['Li, Zhiping', 'Li, Jinsong', 'Zhang, Yandong', 'Li, Lin', 'Ma, Limin', 'Li, Dan', 'Gao, Feng', 'Xia, Zhiping']",Virol J,,,True
85c008e20de23c6313b57d7e638a61c3c611d315,PMC,Detection of human coronavirus strain HKU1 in a 2 years old girl with asthma exacerbation caused by acute pharyngitis,http://dx.doi.org/10.1186/1743-422X-9-142,PMC3439358,22873773,CC BY,"Respiratory viral infections can trigger asthma attack which may lead to sever morbidity. In this report, using molecular methods, we show the chronological association between human coronavirus - HKU1 infection and asthma exacerbation in a two years and seven months old asthmatic girl who was not under treatment and was otherwise healthy.",2012 Aug 3,"['Amini, Razieh', 'Jahanshiri, Fatemeh', 'Amini, Yasaman', 'Sekawi, Zamberi', 'Jalilian, Farid Azizi']",Virol J,,,True
d4535a63a31f97c7564ddf87608bc8b116ba0df0,PMC,"Sentinel Surveillance of Influenza-Like Illness in Two Hospitals in Maracay, Venezuela: 2006–2010",http://dx.doi.org/10.1371/journal.pone.0044511,PMC3439372,22984519,CC0,"BACKGROUND: Limited information exists on the epidemiology of acute febrile respiratory illnesses in tropical South American countries such as Venezuela. The objective of the present study was to examine the epidemiology of influenza-like illness (ILI) in two hospitals in Maracay, Venezuela. METHODOLOGY/PRINCIPAL FINDINGS: We performed a prospective surveillance study of persons with ILI who presented for care at two hospitals in Maracay, Venezuela, from October 2006 to December 2010. A respiratory specimen and clinical information were obtained from each participant. Viral isolation and identification with immunofluorescent antibodies and molecular methods were employed to detect respiratory viruses such as adenovirus, influenza A and B, parainfluenza, and respiratory sincytial virus, among others. There were 916 participants in the study (median age: 17 years; range: 1 month – 86 years). Viruses were identified in 143 (15.6%) subjects, and one participant was found to have a co-infection with more than one virus. Influenza viruses, including pandemic H1N1 2009, were the most frequently detected pathogens, accounting for 67.4% (97/144) of the viruses detected. Adenovirus (15/144), parainfluenza virus (13/144), and respiratory syncytial virus (11/144) were also important causes of ILI in this study. Pandemic H1N1 2009 virus became the most commonly isolated influenza virus during its initial appearance in 2009. Two waves of the pandemic were observed: the first which peaked in August 2009 and the second - higher than the preceding - that peaked in October 2009. In 2010, influenza A/H3N2 re-emerged as the most predominant respiratory virus detected. CONCLUSIONS/SIGNIFICANCE: Influenza viruses were the most commonly detected viral organisms among patients with acute febrile respiratory illnesses presenting at two hospitals in Maracay, Venezuela. Pandemic H1N1 2009 influenza virus did not completely replace other circulating influenza viruses during its initial appearance in 2009. Seasonal influenza A/H3N2 was the most common influenza virus in the post-pandemic phase.",2012 Sep 11,"['Comach, Guillermo', 'Teneza-Mora, Nimfa', 'Kochel, Tadeusz J.', 'Espino, Carlos', 'Sierra, Gloria', 'Camacho, Daria E.', 'Laguna-Torres, V. Alberto', 'Garcia, Josefina', 'Chauca, Gloria', 'Gamero, Maria E.', 'Sovero, Merly', 'Bordones, Slave', 'Villalobos, Iris', 'Melchor, Angel', 'Halsey, Eric S.']",PLoS One,,,True
e95f81436f54620002c9fc909ba8ff591006bf27,PMC,"Surveillance and Genome Analysis of Human Bocavirus in Patients with Respiratory Infection in Guangzhou, China",http://dx.doi.org/10.1371/journal.pone.0044876,PMC3439446,22984581,CC BY,"Human bocavirus (HBoV) is a novel parvovirus associated with respiratory tract diseases and gastrointestinal illness in adult and pediatric patients throughout the world. To investigate the epidemiological and genetic variation of HBoV in Guangzhou, South China, we screened 3460 throat swab samples from 1686 children and 1774 adults with acute respiratory infection symptoms for HBoV between March 2010 and February 2011, and analyzed the complete genome sequence of 2 HBoV strains. Specimens were screened for HBoV by real-time PCR and other 6 common respiratory viruses by RT-PCR or PCR. HBoV was detected in 58 (1.68%) out of 3460 samples, mostly from pediatric patients (52/58) and inpatient children (47/58). Six adult patients were detected as HBoV positive and 5 were emergency cases. Of these HBoV positive cases, 19 (32.76%) had co-pathogens including influenza virus (n = 5), RSV (n = 5), parainfluenza (n = 4), adenovirus (n = 1), coronavirus (n = 7). The complete genome sequences of 2 HBoVs strains (Genbank no. JN794565 and JN794566) were analyzed. Phylogenetic analysis showed that the 2 HBoV strains were HBoV1, and were most genetically close to ST2 (GenBank accession number DQ0000496). Recombination analysis confirmed that HBoV strain GZ9081 was an intra–genotype recombinant strain among HBoV1 variants.",2012 Sep 11,"['Xu, Lin', 'He, Xia', 'Zhang, Ding-mei', 'Feng, Fa-shen', 'Wang, Zhu', 'Guan, Lin-lin', 'Wu, Jue-heng', 'Zhou, Rong', 'Zheng, Bo-jian', 'Yuen, Kwok-yung', 'Li, Meng-feng', 'Cao, Kai-yuan']",PLoS One,,,True
5eb90019b82d03c01d91fd62ca9ba89d60814f82,PMC,Intense Co-Circulation of Non-Influenza Respiratory Viruses during the First Wave of Pandemic Influenza pH1N1/2009: A Cohort Study in Reunion Island,http://dx.doi.org/10.1371/journal.pone.0044755,PMC3440351,22984554,CC BY,"OBJECTIVE: The aim of the present study was to weigh up, at the community level, the respective roles played by pandemic Influenza (pH1N1) virus and co-circulating human Non-Influenza Respiratory Viruses (NIRVs) during the first wave of the 2009 pH1N1 pandemic. METHODS: A population-based prospective cohort study was conducted in Reunion Island during the austral winter 2009 (weeks 30–44) that allowed identification of 125 households with at least one member who developed symptoms of Influenza-like illness (ILI). Three consecutive nasal swabs were collected from each household member (443 individuals) on day 0, 3 and 8 post-ILI report and tested for pH1N1 and 15 NIRVs by RT-PCR. RESULTS: Two successive waves of viral infections were identified: a first wave (W33–37) when pH1N1 was dominant and co-circulated with NIRVs, sharply interrupted by a second wave (W38–44), almost exclusively composed of NIRVs, mainly human Rhinoviruses (hRV) and Coronaviruses (hCoV). Data suggest that some interference may occur between NIRVs and pH1N1 when they co-circulate within the same household, where NIRVs were more likely to infect pH1N1 negative individuals than pH1N1 positive peers (relative risk: 3.13, 95% CI: 1.80–5.46, P<0.001). Viral shedding was significantly shorter (P = 0.035) in patients who were co-infected by pH1N1 and NIRV or by two different NIRVs compared to those who were infected with only one virus, whatever this virus was (pH1N1 or NIRVs). Although intense co-circulation of NIRVs (especially hRV) likely brought pH1N1 under the detection threshold, it did not prevent spread of the pandemic Influenza virus within the susceptible population nor induction of an extensive herd immunity to it. CONCLUSION: Our results suggest that NIRV co-infections during Influenza epidemics may act as cofactors that contribute to shape an outbreak and modulate the attack rate. They further warrant broad spectrum studies to fully understand viral epidemics.",2012 Sep 12,"['Pascalis, Hervé', 'Temmam, Sarah', 'Turpin, Magali', 'Rollot, Olivier', 'Flahault, Antoine', 'Carrat, Fabrice', 'de Lamballerie, Xavier', 'Gérardin, Patrick', 'Dellagi, Koussay']",PLoS One,,,True
60643032cb50195802cf9a11f268e7301d4ad61a,PMC,Serum Levels of Gelatinase Associated Lipocalin as Indicator of the Inflammatory Status in Coronary Artery Disease,http://dx.doi.org/10.1155/2012/189797,PMC3440856,22988542,CC BY,"Background. Atherosclerosis is a chronic inflammatory disease and the acute clinical manifestations represent acute on chronic inflammation. Neutrophil gelatinase-associated lipocalin (NGAL) is found in the granules of human neutrophils, with many diverse functions. The aim of this study was to evaluate the hypothesis that levels NGAL in blood may reflect the inflammatory process in various stages of coronary artery disease. Methods. We studied 140 patients, with SA 40, UA 35, NSTEMI 40, and STEMI 25, and 20 healthy controls. Serum NGAL was measured upon admission and before coronary angiography. Results. Significant differences were observed in median serum-NGAL(ng/mL) between patients with SA (79.23 (IQR, 37.50–100.32)), when compared with UA (108.00 (68.34–177.59)), NSTEMI (166.49 (109.24–247.20)), and STEMI (178.63 (111.18–305.92)) patients and controls (50.31 (44.30–69.78)) with significant incremental value from SA to STEMI. We observed a positive and significant correlation between serum-NGAL and hs-CRP (spearman coefficient rho = 0.685, P < 0.0001) as well as with neutrophil counts (r = 0.511, P < 0.0001). Conclusions. In patients with coronary artery disease serum levels of NGAL increase and reflect the degree of inflammatory process. In patients with acute coronary syndromes, serum levels of NGAL have high negative predictive value and reflecting the inflammatory status could show the severity of coronary clinical syndrome.",2012 Sep 4,"['Kafkas, Nikolaos', 'Demponeras, Christos', 'Zoubouloglou, Filitsa', 'Spanou, Loukia', 'Babalis, Dimitrios', 'Makris, Konstantinos']",Int J Inflam,,,True
cd1b2d233dba9a6446e41588ecf62f7030b5c75d,PMC,Receptor Usage and the Pathogenesis in Acute and Chronic Virus Infections,http://dx.doi.org/10.3389/fmicb.2012.00289,PMC3441196,23024639,CC BY,,2012 Aug 8,"['Tsunetsugu-Yokota, Yasuko', 'Terahara, Kazutaka']",Front Microbiol,,,True
6f3c5be389b060803e0eaa4727b6180637168dad,PMC,Activity based protein profiling to detect serine hydrolase alterations in virus infected cells,http://dx.doi.org/10.3389/fmicb.2012.00308,PMC3441198,23024641,CC BY,"Activity-based protein profiling (ABPP) is a newly emerging technique that uses active site-directed probes to monitor the functional status of enzymes. Serine hydrolases are one of the largest families of enzymes in mammals. More than 200 serine hydrolases have been identified, but little is known about their specific roles. Serine hydrolases are involved in a variety of physiological functions, including digestion, immune response, blood coagulation, and reproduction. ABPP has been used recently to investigate host–virus interactions and to understand the molecular pathogenesis of virus infections. Monitoring the altered serine hydrolases during viral infection gives insight into the catalytic activity of these enzymes that will help to identify novel targets for diagnostic and therapeutic application. This review presents the usefulness of ABPP in detecting and analyzing functional annotation of host cell serine hydrolases as a result of host–virus interaction.",2012 Aug 22,"['Shahiduzzaman, Md.', 'Coombs, Kevin M.']",Front Microbiol,,,True
7398c3a708a291677e55854601f643ba41d79916,PMC,Arapan-S: a fast and highly accurate whole-genome assembly software for viruses and small genomes,http://dx.doi.org/10.1186/1756-0500-5-243,PMC3441218,22591859,CC BY,"BACKGROUND: Genome assembly is considered to be a challenging problem in computational biology, and has been studied extensively by many researchers. It is extremely difficult to build a general assembler that is able to reconstruct the original sequence instead of many contigs. However, we believe that creating specific assemblers, for solving specific cases, will be much more fruitful than creating general assemblers. FINDINGS: In this paper, we present Arapan-S, a whole-genome assembly program dedicated to handling small genomes. It provides only one contig (along with the reverse complement of this contig) in many cases. Although genomes consist of a number of segments, the implemented algorithm can detect all the segments, as we demonstrate for Influenza Virus A. The Arapan-S program is based on the de Bruijn graph. We have implemented a very sophisticated and fast method to reconstruct the original sequence and neglect erroneous k-mers. The method explores the graph by using neither the shortest nor the longest path, but rather a specific and reliable path based on the coverage level or k-mers’ lengths. Arapan-S uses short reads, and it was tested on raw data downloaded from the NCBI Trace Archive. CONCLUSIONS: Our findings show that the accuracy of the assembly was very high; the result was checked against the European Bioinformatics Institute (EBI) database using the NCBI BLAST Sequence Similarity Search. The identity and the genome coverage was more than 99%. We also compared the efficiency of Arapan-S with other well-known assemblers. In dealing with small genomes, the accuracy of Arapan-S is significantly higher than the accuracy of other assemblers. The assembly process is very fast and requires only a few seconds. Arapan-S is available for free to the public. The binary files for Arapan-S are available through http://sourceforge.net/projects/dnascissor/files/.",2012 May 16,"['Sahli, Mohammed', 'Shibuya, Tetsuo']",BMC Res Notes,,,True
d94c4d8b7d45f77cb6080edf6beae9d4bfb99fb2,PMC,Temporal Percolation of the Susceptible Network in an Epidemic Spreading,http://dx.doi.org/10.1371/journal.pone.0044188,PMC3441612,23028498,CC BY,"In this work, we study the evolution of the susceptible individuals during the spread of an epidemic modeled by the susceptible-infected-recovered (SIR) process spreading on the top of complex networks. Using an edge-based compartmental approach and percolation tools, we find that a time-dependent quantity [Image: see text], namely, the probability that a given neighbor of a node is susceptible at time [Image: see text], is the control parameter of a node void percolation process involving those nodes on the network not-reached by the disease. We show that there exists a critical time [Image: see text] above which the giant susceptible component is destroyed. As a consequence, in order to preserve a macroscopic connected fraction of the network composed by healthy individuals which guarantee its functionality, any mitigation strategy should be implemented before this critical time [Image: see text]. Our theoretical results are confirmed by extensive simulations of the SIR process.",2012 Sep 13,"['Valdez, Lucas Daniel', 'Macri, Pablo Alejandro', 'Braunstein, Lidia Adriana']",PLoS One,,,True
7a97d30ce4a24ab47740cf3bbddf7cacd554e84d,PMC,Temporal Percolation of the Susceptible Network in an Epidemic Spreading,http://dx.doi.org/10.1371/journal.pone.0044188,PMC3441612,23028498,CC BY,"In this work, we study the evolution of the susceptible individuals during the spread of an epidemic modeled by the susceptible-infected-recovered (SIR) process spreading on the top of complex networks. Using an edge-based compartmental approach and percolation tools, we find that a time-dependent quantity [Image: see text], namely, the probability that a given neighbor of a node is susceptible at time [Image: see text], is the control parameter of a node void percolation process involving those nodes on the network not-reached by the disease. We show that there exists a critical time [Image: see text] above which the giant susceptible component is destroyed. As a consequence, in order to preserve a macroscopic connected fraction of the network composed by healthy individuals which guarantee its functionality, any mitigation strategy should be implemented before this critical time [Image: see text]. Our theoretical results are confirmed by extensive simulations of the SIR process.",2012 Sep 13,"['Valdez, Lucas Daniel', 'Macri, Pablo Alejandro', 'Braunstein, Lidia Adriana']",PLoS One,,,True
a28353cd5af668e408edfbc98b21224f3b04c232,PMC,Temporal patterns of charcoal burning suicides among the working age population in Hong Kong SAR: the influence of economic activity status and sex,http://dx.doi.org/10.1186/1471-2458-12-505,PMC3443008,22770504,CC BY,"BACKGROUND: Charcoal burning in a sealed room has recently emerged as the second most common suicide means in Hong Kong, causing approximately 200 deaths each year. As charcoal burning suicide victims have a unique sociodemographic profile (i.e., predominantly economically active men), they may commit suicide at specific times. However, little is known about the temporal patterns of charcoal burning suicides. METHODS: Suicide data from 2001 to 2008 on victims of usual working age (20–59) were obtained from the registered death files of the Census and Statistics Department of Hong Kong. A total of 1649 cases of charcoal burning suicide were analyzed using a two-step procedure, which first examined the temporal asymmetries in the incidence of suicide, and second investigated whether these asymmetries were influenced by sex and/or economic activity status. Poisson regression analyses were employed to model the monthly and daily patterns of suicide by economic activity status and sex. RESULTS: Our findings revealed pronounced monthly and daily temporal variations in the pattern of charcoal burning suicides in Hong Kong. Consistent with previous findings on overall suicide deaths, there was an overall spring peak in April, and Monday was the common high risk day for all groups. Although sex determined the pattern of variation in charcoal burning suicides, the magnitude of the variation was influenced by the economic activity status of the victims. CONCLUSION: The traditional classification of suicide methods as either violent or nonviolent tends to elide the temporal variations of specific methods. The interaction between sex and economic activity status observed in the present study indicates that sex should be taken into consideration when investigating the influence of economic activity status on temporal variations of suicide. This finding also suggests that suicide prevention efforts should be both time- and subgroup-specific.",2012 Jul 6,"['Law, Chi-kin', 'Leung, Candi MC']",BMC Public Health,,,True
c0f496f49f4b2dea73cf8c184ff21275bf706908,PMC,Porcine reproductive and respiratory syndrome virus nonstructural protein 2 contributes to NF-κB activation,http://dx.doi.org/10.1186/1743-422X-9-83,PMC3443020,22546080,CC BY,"BACKGROUND: Nuclear factor-kappaB (NF-κB) is an inducible transcription factor that plays a key role in inflammation and immune responses, as well as in the regulation of cell proliferation and survival. Previous studies by our group and others have demonstrated that porcine reproductive and respiratory syndrome virus (PRRSV) infection could activate NF-κB in MARC-145 cells and alveolar macrophages. The nucleocapsid (N) protein was identified as an NF-κB activator among the structural proteins encoded by PRRSV; however, it remains unclear whether the nonstructural proteins (Nsps) contribute to NF-κB activation. In this study, we identified which Nsps can activate NF-κB and investigated the potential mechanism(s) by which they act. RESULTS: By screening the individual Nsps of PRRSV strain WUH3, Nsp2 exhibited great potential to activate NF-κB in MARC-145 and HeLa cells. Overexpression of Nsp2 induced IκBα degradation and nuclear translocation of NF-κB. Furthermore, Nsp2 also induced NF-κB-dependent inflammatory factors, including interleukin (IL)-6, IL-8, COX-2, and RANTES. Compared with the Nsp2 of the classical PRRSV strain, the Nsp2 of highly pathogenic PRRSV (HP-PRRSV) strains that possess a 30 amino acid (aa) deletion in Nsp2 displayed greater NF-κB activation. However, the 30-aa deletion was demonstrated to not be associated with NF-κB activation. Further functional domain analyses revealed that the hypervariable region (HV) of Nsp2 was essential for NF-κB activation. CONCLUSIONS: Taken together, these data indicate that PRRSV Nsp2 is a multifunctional protein participating in the modulation of host inflammatory response, which suggests an important role of Nsp2 in pathogenesis and disease outcomes.",2012 Apr 30,"['Fang, Ying', 'Fang, Liurong', 'Wang, Yang', 'Lei, Yingying', 'Luo, Rui', 'Wang, Dang', 'Chen, Huanchun', 'Xiao, Shaobo']",Virol J,,,True
ffbe34e6cdad2e0807c420ddee33b842e38e219d,PMC,A novel hierarchical clustering algorithm for gene sequences,http://dx.doi.org/10.1186/1471-2105-13-174,PMC3443659,22823405,CC BY,"BACKGROUND: Clustering DNA sequences into functional groups is an important problem in bioinformatics. We propose a new alignment-free algorithm, mBKM, based on a new distance measure, DMk, for clustering gene sequences. This method transforms DNA sequences into the feature vectors which contain the occurrence, location and order relation of k-tuples in DNA sequence. Afterwards, a hierarchical procedure is applied to clustering DNA sequences based on the feature vectors. RESULTS: The proposed distance measure and clustering method are evaluated by clustering functionally related genes and by phylogenetic analysis. This method is also compared with BlastClust, CD-HIT-EST and some others. The experimental results show our method is effective in classifying DNA sequences with similar biological characteristics and in discovering the underlying relationship among the sequences. CONCLUSIONS: We introduced a novel clustering algorithm which is based on a new sequence similarity measure. It is effective in classifying DNA sequences with similar biological characteristics and in discovering the relationship among the sequences.",2012 Jul 23,"['Wei, Dan', 'Jiang, Qingshan', 'Wei, Yanjie', 'Wang, Shengrui']",BMC Bioinformatics,,,True
0f7c4b6a69f7c82ec245cf64dada9150d1e4b831,PMC,"Herbal Products: Benefits, Limits, and Applications in Chronic Liver Disease",http://dx.doi.org/10.1155/2012/837939,PMC3443820,22991573,CC BY,"Complementary and alternative medicine soughts and encompasses a wide range of approaches; its use begun in ancient China at the time of Xia dynasty and in India during the Vedic period, but thanks to its long-lasting curative effect, easy availability, natural way of healing, and poor side-effects it is gaining importance throughout the world in clinical practice. We conducted a review describing the effects and the limits of using herbal products in chronic liver disease, focusing our attention on those most known, such as quercetin or curcumin. We tried to describe their pharmacokinetics, biological properties, and their beneficial effects (as antioxidant role) in metabolic, alcoholic, and viral hepatitis (considering that oxidative stress is the common pathway of chronic liver diseases of different etiology). The main limit of applicability of CAM comes from the lacking of randomized, placebo-controlled clinical trials giving a real proof of efficacy of those products, so that anecdotal success and personal experience are frequently the driving force for acceptance of CAM in the population.",2012 Sep 6,"['Del Prete, Anna', 'Scalera, Antonella', 'Iadevaia, Maddalena Diana', 'Miranda, Agnese', 'Zulli, Claudio', 'Gaeta, Laura', 'Tuccillo, Concetta', 'Federico, Alessandro', 'Loguercio, Carmelina']",Evid Based Complement Alternat Med,,,True
474978e3a0f1a8064083d7ae5136b968d10184ab,PMC,Transcriptional Regulation of Flotillins by the Extracellularly Regulated Kinases and Retinoid X Receptor Complexes,http://dx.doi.org/10.1371/journal.pone.0045514,PMC3445523,23029064,CC BY,"Flotillin-1 and flotillin-2 are important regulators of signal transduction pathways such as growth factor signaling. Flotillin expression is increased under pathological conditions such as neurodegenerative disorders and cancer. Despite their importance for signal transduction, very little is known about the transcriptional regulation of flotillins. Here, we analyzed the expression of flotillins at transcriptional level and identified flotillins as downstream targets of the mitogen activated kinases ERK1/2. The promoter activity of flotillins was increased upon growth factor stimulation in a MAPK dependent manner. Overexpression of serum response factor or early growth response gene 1 resulted in increased flotillin mRNA and protein expression. Furthermore, both promoter activity and expression of endogenous flotillins were increased upon treatment with retinoic acid or by overexpression of the retinoid X receptor and its binding partners RARα and PPARγ. Our data indicate that the expression of flotillins, which can be detected in all cultured cells, is fine-tuned in response to various external stimuli. This regulation may be critical for the outcome of signaling cascades in which flotillins are known to be involved.",2012 Sep 18,"['Banning, Antje', 'Ockenga, Wymke', 'Finger, Fabian', 'Siebrasse, Philipp', 'Tikkanen, Ritva']",PLoS One,,,True
b11f198de26a3035fb312becd5eeac9a25d5f2c1,PMC,Performance of VIDISCA-454 in Feces-Suspensions and Serum,http://dx.doi.org/10.3390/v4081328,PMC3446766,23012629,CC BY,"Virus discovery combining sequence unbiased amplification with next generation sequencing is now state-of-the-art. We have previously determined that the performance of the unbiased amplification technique which is operational at our institute, VIDISCA-454, is efficient when respiratory samples are used as input. The performance of the assay is, however, not known for other clinical materials like blood or stool samples. Here, we investigated the sensitivity of VIDISCA-454 with feces-suspensions and serum samples that are positive and that have been quantified for norovirus and human immunodeficiency virus type 1, respectively. The performance of VIDISCA-454 in serum samples was equal to its performance in respiratory material, with an estimated lower threshold of 1,000 viral genome copies. The estimated threshold in feces-suspension is around 200,000 viral genome copies. The decreased sensitivity in feces suspension is mainly due to sequences that share no recognizable identity with known sequences. Most likely these sequences originate from bacteria and phages which are not completely sequenced.",2012 Aug 22,"['de Vries, Michel', 'Oude Munnink, Bas B.', 'Deijs, Martin', 'Canuti, Marta', 'Koekkoek, Sylvie M.', 'Molenkamp, Richard', 'Bakker, Margreet', 'Jurriaans, Suzanne', 'van Schaik, Barbera D. C.', 'Luyf, Angela C.', 'Olabarriaga, Silvia D.', 'van Kampen, Antoine H. C.', 'van der Hoek, Lia']",Viruses,,,True
604397da653890b54d4af23b45adab3365e1f042,PMC,Functional Analysis of Rift Valley Fever Virus NSs Encoding a Partial Truncation,http://dx.doi.org/10.1371/journal.pone.0045730,PMC3446906,23029207,CC BY,"Rift Valley fever virus (RVFV), belongs to genus Phlebovirus of the family Bunyaviridae, causes high rates of abortion and fetal malformation in infected ruminants as well as causing neurological disorders, blindness, or lethal hemorrhagic fever in humans. RVFV is classified as a category A priority pathogen and a select agent in the U.S., and currently there are no therapeutics available for RVF patients. NSs protein, a major virulence factor of RVFV, inhibits host transcription including interferon (IFN)-β mRNA synthesis and promotes degradation of dsRNA-dependent protein kinase (PKR). NSs self-associates at the C-terminus 17 aa., while NSs at aa.210–230 binds to Sin3A-associated protein (SAP30) to inhibit the activation of IFN-β promoter. Thus, we hypothesize that NSs function(s) can be abolished by truncation of specific domains, and co-expression of nonfunctional NSs with intact NSs will result in the attenuation of NSs function by dominant-negative effect. Unexpectedly, we found that RVFV NSs truncated at aa. 6–30, 31–55, 56–80, 81–105, 106–130, 131–155, 156–180, 181–205, 206–230, 231–248 or 249–265 lack functions of IFN–β mRNA synthesis inhibition and degradation of PKR. Truncated NSs were less stable in infected cells, while nuclear localization was inhibited in NSs lacking either of aa.81–105, 106–130, 131–155, 156–180, 181–205, 206–230 or 231–248. Furthermore, none of truncated NSs had exhibited significant dominant-negative functions for NSs-mediated IFN-β suppression or PKR degradation upon co-expression in cells infected with RVFV. We also found that any of truncated NSs except for intact NSs does not interact with RVFV NSs even in the presence of intact C-terminus self-association domain. Our results suggest that conformational integrity of NSs is important for the stability, cellular localization and biological functions of RVFV NSs, and the co-expression of truncated NSs does not exhibit dominant-negative phenotype.",2012 Sep 19,"['Head, Jennifer A.', 'Kalveram, Birte', 'Ikegami, Tetsuro']",PLoS One,,,True
96f1b9981028f5954b8f93c8dec9a69c236c124d,PMC,Clinical Impact of Infection with Pandemic Influenza (H1N1) 2009 Virus in Naïve Nucleus and Multiplier Pig Herds in Norway,http://dx.doi.org/10.1155/2011/163745,PMC3447284,23074653,CC BY,The Norwegian pig population has been free from influenza viruses until 2009. The pandemic influenza outbreak during the autumn 2009 provided an opportunity to study the clinical impact of this infection in an entirely naïve pig population. This paper describes the results of a case-control study on the clinical impact of pandemic influenza (H1N1) 2009 infection in the nucleus and multiplier herds in Norway. The infection spread readily and led to seroconversion of 42% of the Norwegian nucleus and multiplier herds within a year. Positive and negative herds were identified based on surveillance data from the Norwegian Veterinary Institute. Telephone interviews were conducted with pig herd owners or managers between November 2010 and January 2011. Pigs with clinical signs were reported from 40% of the case herds with varying morbidity and duration of respiratory disease and reduced reproductive performance. Clinical signs were reported in all age groups.,2011 Dec 22,"['Grøntvedt, Carl Andreas', 'Er, Chiek', 'Gjerset, Britt', 'Germundsson, Anna', 'Framstad, Tore', 'Brun, Edgar', 'Jørgensen, Anne', 'Lium, Bjørn']",Influenza Res Treat,,,True
60abca9911a64805e51aa8deb70bb238c2f3d414,PMC,Influenza-Associated Mortality in Georgia (2009–2011),http://dx.doi.org/10.1155/2012/480763,PMC3447290,23074667,CC BY,"We analyzed data from NCDCPH Georgia where samples from outpatients with influenza-like illness (ILI) and inpatients with severe acute respiratory syndrome (SARI) are referred for testing on influenza virus using PCR analysis. During 2009-2010 and 2010-2011 influenza pandemics total number of the laboratory-confirmed influenza cases were 1286 with 33 deaths (all of them influenza type A) and 1203 (51.4% type A) with 44 deaths, respectively. At least one underlying medical condition was reported in 70.7% (for pandemic influenza strain) and 96% (for influenza type B) of deaths. Predominating preexisting condition was coronary heart disease.",2012 Aug 15,"['Butsashvili, Maia', 'Kandelaki, George', 'Zakhashvili, Khatuna', 'Machablishvili, Ana', 'Avaliani, Nata']",Influenza Res Treat,,,True
3e8d986f56b6afb805e70236871627835e68372c,PMC,Predictive and Reactive Distribution of Vaccines and Antivirals during Cross-Regional Pandemic Outbreaks,http://dx.doi.org/10.1155/2011/579597,PMC3447295,23074658,CC BY,"As recently pointed out by the Institute of Medicine, the existing pandemic mitigation models lack the dynamic decision support capability. We develop a large-scale simulation-driven optimization model for generating dynamic predictive distribution of vaccines and antivirals over a network of regional pandemic outbreaks. The model incorporates measures of morbidity, mortality, and social distancing, translated into the cost of lost productivity and medical expenses. The performance of the strategy is compared to that of the reactive myopic policy, using a sample outbreak in Fla, USA, with an affected population of over four millions. The comparison is implemented at different levels of vaccine and antiviral availability and administration capacity. Sensitivity analysis is performed to assess the impact of variability of some critical factors on policy performance. The model is intended to support public health policy making for effective distribution of limited mitigation resources.",2011 Jun 5,"['Uribe-Sánchez, Andrés', 'Savachkin, Alex']",Influenza Res Treat,,,True
c66d7cf6243be684d42751e19f4f9c27ca8a1f3b,PMC,A Novel Vaccine Using Nanoparticle Platform to Present Immunogenic M2e against Avian Influenza Infection,http://dx.doi.org/10.1155/2011/126794,PMC3447297,23074652,CC BY,"Using peptide nanoparticle technology, we have designed two novel vaccine constructs representing M2e in monomeric (Mono-M2e) and tetrameric (Tetra-M2e) forms. Groups of specific pathogen free (SPF) chickens were immunized intramuscularly with Mono-M2e or Tetra-M2e with and without an adjuvant. Two weeks after the second boost, chickens were challenged with 107.2 EID50 of H5N2 low pathogenicity avian influenza (LPAI) virus. M2e-specific antibody responses to each of the vaccine constructs were tested by ELISA. Vaccinated chickens exhibited increased M2e-specific IgG responses for each of the constructs as compared to a non-vaccinated group. However, the vaccine construct Tetra-M2e elicited a significantly higher antibody response when it was used with an adjuvant. On the other hand, virus neutralization assays indicated that immune protection is not by way of neutralizing antibodies. The level of protection was evaluated using quantitative real time PCR at 4, 6, and 8 days post-challenge with H5N2 LPAI by measuring virus shedding from trachea and cloaca. The Tetra-M2e with adjuvant offered statistically significant (P < 0.05) protection against subtype H5N2 LPAI by reduction of the AI virus shedding. The results suggest that the self-assembling polypeptide nanoparticle shows promise as a potential platform for a development of a vaccine against AI.",2011 Jan 12,"['Babapoor, Sankhiros', 'Neef, Tobias', 'Mittelholzer, Christian', 'Girshick, Theodore', 'Garmendia, Antonio', 'Shang, Hongwei', 'Khan, Mazhar I.', 'Burkhard, Peter']",Influenza Res Treat,,,True
648e9c790e9707c35271988c3f86aa147a9eda05,PMC,"Efficacy and Safety of CVT-E002, a Proprietary Extract of Panax quinquefolius in the Prevention of Respiratory Infections in Influenza-Vaccinated Community-Dwelling Adults: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Trial",http://dx.doi.org/10.1155/2011/759051,PMC3447298,23074661,CC BY,"CVT-E002 (a proprietary extract) was found to be effective in the prevention of upper respiratory infections (URIs) in healthy adults, and institutionalized and community-dwelling seniors. A multicenter, randomized, double-blind, placebo-controlled trial was carried out to determine effects of CVT-E002 in the prevention of URIs in influenza-vaccinated community-dwelling adults. 783 community-dwelling adults were randomized to receive placebo, 400 mg or 800 mg treatment/d (1 : 1 : 1) for 6 months. Primary analysis on the incidence of laboratory-confirmed-clinical URIs (LCCUs), including influenza A and B, was performed on those receiving at least one dose. Secondary analysis was performed on study completers and included incidence, severity, and duration of URIs meeting a Jackson-based criteria and safety of CVT-E002. The incidence of LCCUs in the ITT group was 5.5%, 5.2%, and 4.6% in the placebo, 400 mg and 800 mg groups, respectively (P = 0.89). Jackson-confirmed URIs were significantly lower in the treated groups (P < 0.04). CVT-E002 supplementation reduced the severity and duration of Jackson-confirmed URIs. The results indicate that CVT-E002 can be safely used by similar groups and may prevent symptoms of URIs; larger sample size is warranted.",2011 Jul 20,"['McElhaney, Janet E.', 'Simor, Andrew E.', 'McNeil, Shelly', 'Predy, Gerald N.']",Influenza Res Treat,,,True
a699cfdfda9ccc5ccb41e946a63113106b39148d,PMC,Factors Associated with Increased Risk Perception of Pandemic Influenza in Australia,http://dx.doi.org/10.1155/2010/947906,PMC3447299,23074650,CC BY,"The aim of this study was to assess factors associated with increased risk perception of pandemic influenza in Australia. The sample consisted of 2081 Australian adults aged 16 years and older who completed a short three item pandemic influenza question module which was incorporated into the NSW Health Adult Population Health Survey during the first quarter of 2007. After adjusting for covariates, multivariate analysis indicated that those living in rural regions were significantly more likely to perceive a high risk that a pandemic influenza would occur, while those with poor self-rated health perceived both a high likelihood of pandemic and high concern that self/family would be directly affected were such an event to occur. Those who spoke a language other than English at home and those on low incomes and younger people (16–24 years) were significantly more likely to have changed the way they lived their lives due to the possibility of pandemic influenza, compared to those who spoke only English at home, middle-high income earners, and older age groups, respectively. This data provides an Australian population baseline against which the risk perceptions of demographic subgroups regarding the current, and potential future pandemics, can be compared and monitored.",2010 Jul 20,"['Jacobs, Jennifer', 'Taylor, Melanie', 'Agho, Kingsley', 'Stevens, Garry', 'Barr, Margo', 'Raphael, Beverley']",Influenza Res Treat,,,True
47939863a50677044e74f69efc9b22a80d37562f,PMC,Blow Flies Were One of the Possible Candidates for Transmission of Highly Pathogenic H5N1 Avian Influenza Virus during the 2004 Outbreaks in Japan,http://dx.doi.org/10.1155/2011/652652,PMC3447300,23074659,CC BY,"The 2003-2004 H5N1 highly pathogenic avian influenza (HPAI) outbreaks in Japan were the first such outbreaks in 79 years in Japan. Epidemic outbreaks have been occurring in Southeast Asia, with the most recent in 2010. Knowledge of the transmission route responsible for the HPAI outbreaks in these countries remains elusive. Our studies strongly suggested that field and laboratory studies focusing on mechanical transmission by blow flies should be considered to control H5N1 avian influenza outbreaks, in particular in epidemic areas, where there are high densities of different fly species throughout the year. In this paper, we review these field and laboratory entomological studies and discuss the possibility of blow flies transmitting H5N1 viruses.",2011 Dec 28,"['Sawabe, Kyoko', 'Hoshino, Keita', 'Isawa, Haruhiko', 'Sasaki, Toshinori', 'Kim, Kyeong Soon', 'Hayashi, Toshihiko', 'Tsuda, Yoshio', 'Kurahashi, Hiromu', 'Kobayashi, Mutsuo']",Influenza Res Treat,,,True
9d0653aa163675efb2e832369ae48761148b43ed,PMC,Experiences after Twenty Months with Pandemic Influenza A (H1N1) 2009 Infection in the Naïve Norwegian Pig Population,http://dx.doi.org/10.1155/2011/206975,PMC3447302,23074654,CC BY,"Pandemic (H1N1) 2009 influenza A virus was detected in Norwegian pigs in October 2009. Until then, Norway was regarded free of swine influenza. Intensified screening revealed 91 positive herds within three months. The virus was rapidly transmitted to the susceptible population, including closed breeding herds with high biosecurity. Humans were important for the introduction as well as spread of the virus to pigs. Mild or no clinical signs were observed in infected pigs. Surveillance of SIV in 2010 revealed that 41% of all the Norwegian pig herds had antibodies to pandemic (H1N1) 2009 virus. Furthermore, this surveillance indicated that pigs born in positive herds after the active phase did not seroconvert, suggesting no ongoing infection in the herds. However, results from surveillance in 2011 show a continuing spread of the infection in many herds, either caused by new introduction or by virus circulation since 2009.",2011 Jan 3,"['Gjerset, B.', 'Er, C.', 'Løtvedt, S.', 'Jørgensen, A.', 'Hungnes, O.', 'Lium, B.', 'Germundsson, A.']",Influenza Res Treat,,,True
85f3c300e460e62364ef4a74fb1289334a5c2317,PMC,Protection conferred by a recombinant Marek’s disease virus that expresses the spike protein from infectious bronchitis virus in specific pathogen-free chicken,http://dx.doi.org/10.1186/1743-422X-9-85,PMC3447679,22559869,CC BY,"BACKGROUND: In many countries, the predominant field isolates of infectious bronchitis virus (IBV) have been classified as QX-like strains since 1996. However, no commercial vaccines that are specific for this type of IBV are currently available. Therefore, there is an urgent need to develop novel vaccines that prevent QX-like IBV infection. RESULTS: A recombinant Marek’s disease virus (MDV), rMDV-S1, that expresses the S1 subunit of the spike (S) protein from the QX-like infectious bronchitis virus (IBV) was constructed by inserting the IBV S1 gene into the genome of the CVI988/Rispens strain of MDV. Specific pathogen-free (SPF) chickens that were vaccinated with rMDV-S1 were protected when challenged with the QX-like IBV. They were observed to have mild clinical signs of disease, a short virus-shedding period and low mortality. Additionally, the rMDV-S1 conferred full protection to chickens against virulent MDV, as did the CVI988/Rispens strain. CONCLUSIONS: Our results demonstrate that rMDV-S1 is an effective and promising recombinant vaccine for the prevention of QX-like IBV infection.",2012 May 4,"['Zhang, Xiaorong', 'Wu, Yantao', 'Huang, Yezhen', 'Liu, Xiufan']",Virol J,,,True
891adb48f822d8e7f4749448ea5e2b4828c9aae5,PMC,"Protective efficacy of a broadly cross-reactive swine influenza DNA vaccine encoding M2e, cytotoxic T lymphocyte epitope and consensus H3 hemagglutinin",http://dx.doi.org/10.1186/1743-422X-9-127,PMC3447699,22738661,CC BY,"BACKGROUND: Pigs have been implicated as mixing reservoir for the generation of new pandemic influenza strains, control of swine influenza has both veterinary and public health significance. Unlike human influenza vaccines, strains used for commercially available swine influenza vaccines are not regularly replaced, making the vaccines provide limited protection against antigenically diverse viruses. It is therefore necessary to develop broadly protective swine influenza vaccines that are efficacious to both homologous and heterologous virus infections. In this study, two forms of DNA vaccines were constructed, one was made by fusing M2e to consensus H3HA (MHa), which represents the majority of the HA sequences of H3N2 swine influenza viruses. Another was made by fusing M2e and a conserved CTL epitope (NP147-155) to consensus H3HA (MNHa). Their protective efficacies against homologous and heterologous challenges were tested. RESULTS: BALB/c mice were immunized twice by particle-mediated epidermal delivery (gene gun) with the two DNA vaccines. It was shown that the two vaccines elicited substantial antibody responses, and MNHa induced more significant T cell-mediated immune response than MHa did. Then two H3N2 strains representative of different evolutional and antigenic clusters were used to challenge the vaccine-immunized mice (homosubtypic challenge). Results indicated that both of the DNA vaccines prevented homosubtypic virus infections completely. The vaccines’ heterologous protective efficacies were further tested by challenging with a H1N1 swine influenza virus and a reassortant 2009 pandemic strain. It was found that MNHa reduced the lung viral titers significantly in both challenge groups, histopathological observation showed obvious reduction of lung pathogenesis as compared to MHa and control groups. CONCLUSIONS: The combined utility of the consensus HA and the conserved M2e and CTL epitope can confer complete and partial protection against homologous and heterologous challenges, respectively, in mouse model. This may provide a basis for the development of universal swine influenza vaccines.",2012 Jun 27,"['Wang, Bin', 'Yu, Hai', 'Yang, Fu-Ru', 'Huang, Meng', 'Ma, Ji-Hong', 'Tong, Guang-Zhi']",Virol J,,,True
8aef75d2d213cab0a2b4661fc9971507863ff9ed,PMC,Use of functional gene arrays for elucidating in situ biodegradation,http://dx.doi.org/10.3389/fmicb.2012.00339,PMC3448134,23049526,CC BY,"Microarrays have revolutionized the study of microbiology by providing a high-throughput method for examining thousands of genes with a single test and overcome the limitations of many culture-independent approaches. Functional gene arrays (FGA) probe a wide range of genes involved in a variety of functions of interest to microbial ecology (e.g., carbon degradation, N fixation, metal resistance) from many different microorganisms, cultured and uncultured. The most comprehensive FGA to date is the GeoChip array, which targets tens of thousands of genes involved in the geochemical cycling of carbon, nitrogen, phosphorus, and sulfur, metal resistance and reduction, energy processing, antibiotic resistance and contaminant degradation as well as phylogenetic information (gyrB). Since the development of GeoChips, many studies have been performed using this FGA and have shown it to be a powerful tool for rapid, sensitive, and specific examination of microbial communities in a high-throughput manner. As such, the GeoChip is well-suited for linking geochemical processes with microbial community function and structure. This technology has been used successfully to examine microbial communities before, during, and after in situ bioremediation at a variety of contaminated sites. These studies have expanded our understanding of biodegradation and bioremediation processes and the associated microorganisms and environmental conditions responsible. This review provides an overview of FGA development with a focus on the GeoChip and highlights specific GeoChip studies involving in situ bioremediation.",2012 Sep 21,"['Nostrand, Joy D. Van', 'He, Zhili', 'Zhou, Jizhong']",Front Microbiol,,,True
72ac928abb4394f723426f2e506d71d4892c1036,PMC,Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis,http://dx.doi.org/10.1371/journal.pone.0045665,PMC3448645,23029170,CC BY,"The negative transcription regulator of the ica locus, TcaR, regulates proteins involved in the biosynthesis of poly-N-acetylglucosamine (PNAG). Absence of TcaR increases PNAG production and promotes biofilm formation in Staphylococci. Previously, the 3D structure of TcaR in its apo form and its complex structure with several antibiotics have been analyzed. However, the detailed mechanism of multiple antibiotic resistance regulator (MarR) family proteins such as TcaR is unclear and only restricted on the binding ability of double-strand DNA (dsDNA). Here we show by electrophoretic mobility shift assay (EMSA), electron microscopy (EM), circular dichroism (CD), and Biacore analysis that TcaR can interact strongly with single-stranded DNA (ssDNA), thereby identifying a new role in MarR family proteins. Moreover, we show that TcaR preferentially binds 33-mer ssDNA over double-stranded DNA and inhibits viral ssDNA replication. In contrast, such ssDNA binding properties were not observed for other MarR family protein and TetR family protein, suggesting that the results from our studies are not an artifact due to simple charge interactions between TcaR and ssDNA. Overall, these results suggest a novel role for TcaR in regulation of DNA replication. We anticipate that the results of this work will extend our understanding of MarR family protein and broaden the development of new therapeutic strategies for Staphylococci.",2012 Sep 21,"['Chang, Yu-Ming', 'Chen, Cammy K. -M.', 'Chang, Yuan-Chih', 'Jeng, Wen-Yih', 'Hou, Ming-Hon', 'Wang, Andrew H. -J.']",PLoS One,,,True
2b91f521c12a736203029e85675120740c3c1810,PMC,Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model,http://dx.doi.org/10.1371/journal.pone.0045842,PMC3454321,23029269,CC BY,"In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV) infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG) expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH)(3)-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines.",2012 Sep 24,"['Cameron, Mark J.', 'Kelvin, Alyson A.', 'Leon, Alberto J.', 'Cameron, Cheryl M.', 'Ran, Longsi', 'Xu, Luoling', 'Chu, Yong-Kyu', 'Danesh, Ali', 'Fang, Yuan', 'Li, Qianjun', 'Anderson, Austin', 'Couch, Ronald C.', 'Paquette, Stephane G.', 'Fomukong, Ndingsa G.', 'Kistner, Otfried', 'Lauchart, Manfred', 'Rowe, Thomas', 'Harrod, Kevin S.', 'Jonsson, Colleen B.', 'Kelvin, David J.']",PLoS One,,,True
f763d5c729b3a02773062e212f3f2632d2ebb574,PMC,"Safety and Efficacy Profile of Echinacea purpurea to Prevent Common Cold Episodes: A Randomized, Double-Blind, Placebo-Controlled Trial",http://dx.doi.org/10.1155/2012/841315,PMC3457740,23024696,CC BY,"Objective. To investigate the safety (risk) and efficacy (benefit) of Echinacea purpurea extract in the prevention of common cold episodes in a large population over a 4-month period. Methods. 755 healthy subjects were allocated to receive either an alcohol extract from freshly harvested E. purpurea (95% herba and 5% root) or placebo. Participants were required to record adverse events and to rate cold-related issues in a diary throughout the investigation period. Nasal secretions were sampled at acute colds and screened for viruses. Results. A total of 293 adverse events occurred with Echinacea and 306 with placebo treatment. Nine and 10% of participants experienced adverse events, which were at least possibly related to the study drug (adverse drug reactions). Thus, the safety of Echinacea was noninferior to placebo. Echinacea reduced the total number of cold episodes, cumulated episode days within the group, and pain-killer medicated episodes. Echinacea inhibited virally confirmed colds and especially prevented enveloped virus infections (P < 0.05). Echinacea showed maximal effects on recurrent infections, and preventive effects increased with therapy compliance and adherence to the protocol. Conclusions. Compliant prophylactic intake of E. purpurea over a 4-month period appeared to provide a positive risk to benefit ratio.",2012 Sep 16,"['Jawad, M.', 'Schoop, R.', 'Suter, A.', 'Klein, P.', 'Eccles, R.']",Evid Based Complement Alternat Med,,,True
7a1329845e6f9569ebad76566c23cf88fd8d5508,PMC,The VP3 Factor from Viruses of Birnaviridae Family Suppresses RNA Silencing by Binding Both Long and Small RNA Duplexes,http://dx.doi.org/10.1371/journal.pone.0045957,PMC3458112,23049903,CC BY,"RNA silencing is directly involved in antiviral defense in a wide variety of eukaryotic organisms, including plants, fungi, invertebrates, and presumably vertebrate animals. The study of RNA silencing-mediated antiviral defences in vertebrates is hampered by the overlap with other antiviral mechanisms; thus, heterologous systems are often used to study the interplay between RNA silencing and vertebrate-infecting viruses. In this report we show that the VP3 protein of the avian birnavirus Infectious bursal disease virus (IBDV) displays, in addition to its capacity to bind long double-stranded RNA, the ability to interact with double-stranded small RNA molecules. We also demonstrate that IBDV VP3 prevents the silencing mediated degradation of a reporter mRNA, and that this silencing suppression activity depends on its RNA binding ability. Furthermore, we find that the anti-silencing activity of IBDV VP3 is shared with the homologous proteins expressed by both insect- and fish-infecting birnaviruses. Finally, we show that IBDV VP3 can functionally replace the well-characterized HCPro silencing suppressor of Plum pox virus, a potyvirus that is unable to infect plants in the absence of an active silencing suppressor. Altogether, our results support the idea that VP3 protects the viral genome from host sentinels, including those of the RNA silencing machinery.",2012 Sep 25,"['Valli, Adrian', 'Busnadiego, Idoia', 'Maliogka, Varvara', 'Ferrero, Diego', 'Castón, José R.', 'Rodríguez, José Francisco', 'García, Juan Antonio']",PLoS One,,,True
3ebbe01c6f991fcc45a9b12f9421acd50d756503,PMC,"Surveillance on secular trends of incidence and mortality for device–associated infection in the intensive care unit setting at a tertiary medical center in Taiwan, 2000–2008: A retrospective observational study",http://dx.doi.org/10.1186/1471-2334-12-209,PMC3458996,22963041,CC BY,"BACKGROUND: Device–associated infection (DAI) plays an important part in nosocomial infection. Active surveillance and infection control are needed to disclose the specific situation in each hospital and to cope with this problem effectively. We examined the rates of DAI by antimicrobial-resistant pathogens, and 30–day and in–hospital mortality in the intensive care unit (ICU). METHODS: Prospective surveillance was conducted in a mixed medical and surgical ICU at a major teaching hospital from 2000 through 2008. Trend analysis was performed and logistic regression was used to assess prognostic factors of mortality. RESULTS: The overall rate of DAIs was 3.03 episodes per 1000 device–days. The most common DAI type was catheter–associated urinary tract infection (3.76 per 1000 urinary catheter–days). There was a decrease in DAI rates in 2005 and rates of ventilator–associated pneumonia (VAP, 3.18 per 1000 ventilator–days) have remained low since then (p < 0.001). The crude rates of 30–day (33.6%) and in–hospital (52.3%) mortality, as well as infection by antibiotic-resistant VAP pathogens also decreased. The most common antimicrobial-resistant pathogens were methicillin–resistant Staphylococcus aureus (94.9%) and imipenem–resistant Acinetobacter baumannii (p < 0.001), which also increased at the most rapid rate. The rate of antimicrobial resistance among Enterobacteriaceae also increased significantly (p < 0.05). After controlling for potentially confounding factors, the DAI was an independent prognostic factor for both 30–day mortality (OR 2.51, 95% confidence interval [CI] 1.99–3.17, p = 0.001) and in–hospital mortality (OR 3.61, 95% CI 2.10–3.25, p < 0.001). CONCLUSIONS: The decrease in the rate of DAI and infection by resistant bacteria on the impact of severe acute respiratory syndrome can be attributed to active infection control and improved adherence after 2003.",2012 Sep 10,"['Chen, Yin-Yin', 'Chen, Liang-Yu', 'Lin, Seng-Yi', 'Chou, Pesus', 'Liao, Shu-Yuan', 'Wang, Fu-Der']",BMC Infect Dis,,,True
0f8451b64b7aa2e642036d79efc1969125c45873,PMC,Association between insertion/deletion polymorphism in angiotensin-converting enzyme gene and acute lung injury/acute respiratory distress syndrome: a meta-analysis,http://dx.doi.org/10.1186/1471-2350-13-76,PMC3459791,22938636,CC BY,"BACKGROUND: A previous meta-analysis reported a positive association between an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) and the risk of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Here, we updated this meta-analysis and additionally assessed the association of this polymorphism with ALI/ARDS mortality. METHODS: We searched electronic databases through October 2011 for the terms “angiotensin-converting enzyme gene”, “acute lung injury”, and “acute respiratory distress syndrome,” and reviewed all studies that reported the relationship of the I/D polymorphism in ACE with ALI/ARDS in humans. Seven studies met the inclusion criteria, comprising 532 ALI/ARDS patients, 3032 healthy controls, and 1432 patients without ALI/ARDS. We used three genetic models: the allele, dominant, and recessive models. RESULTS: The ACE I/D polymorphism was not associated with susceptibility to ALI/ARDS for any genetic model. However, the ACE I/D polymorphism was associated with the mortality risk of ALI/ARDS in Asian subjects ( P(allele) < 0.0001, P(dominant) = 0.001, P(recessive) = 0.002). This finding remained significant after correction for multiple comparisons. CONCLUSIONS: There is a possible association between the ACE I/D polymorphism genotype and the mortality risk of ALI/ARDS in Asians.",2012 Aug 31,"['Matsuda, Akihisa', 'Kishi, Taro', 'Jacob, Asha', 'Aziz, Monowar', 'Wang, Ping']",BMC Med Genet,,,True
739e01113e6c837a1fb973b1ab7e434cc9c27904,PMC,"Differential Effects of IL-12 on Tregs and Non-Treg T Cells: Roles of IFN-γ, IL-2 and IL-2R",http://dx.doi.org/10.1371/journal.pone.0046241,PMC3459844,23029447,CC BY,"Complex interactions between effector T cells and Foxp3(+) regulatory T cells (Treg) contribute to clinical outcomes in cancer, and autoimmune and infectious diseases. Previous work showed that IL-12 reversed Treg-mediated suppression of CD4(+)Foxp3(−) T cell (Tconv) proliferation. We and others have also shown that Tregs express T-bet and IFN-γ at sites of Th1 inflammation and that IL-12 induces IFN-γ production by Tregs in vitro. To investigate whether loss of immunosuppression occurs when IFN-γ is expressed by Tregs we treated mouse lymphocyte cultures with IL-12. IFN-γ expression did not decrease the ability of Tregs to suppress Tconv proliferation. Rather, IL-12 treatment decreased Treg frequency and Foxp3 levels in Tregs. We further showed that IL-12 increased IL-2R expression on Tconv and CD8 T cells, diminished its expression on Tregs and decreased IL-2 production by Tconv and CD8 T cells. Together, these IL-12 mediated changes favored the outgrowth of non-Tregs. Additionally, we showed that treatment with a second cytokine, IL-27, decreased IL-2 expression without augmenting Tconv and CD8 T cell proliferation. Notably, IL-27 only slightly modified levels of IL-2R on non-Treg T cells. Together, these results show that IL-12 has multiple effects that modify the balance between Tregs and non-Tregs and support an important role for relative levels of IL-2R but not for IFN-γ expression in IL-12-mediated reversal of Treg immunosuppression.",2012 Sep 27,"['Zhao, Jingxian', 'Zhao, Jincun', 'Perlman, Stanley']",PLoS One,,,True
d077e86d41dd4161565d2edf1446d8bc4ec5ed0a,PMC,"Genetic Variation in the TNF Gene Is Associated with Susceptibility to Severe Sepsis, but Not with Mortality",http://dx.doi.org/10.1371/journal.pone.0046113,PMC3459853,23029405,CC BY,"BACKGROUND: Tumor necrosis factor (TNF) and TNF receptor superfamily (TNFR)-mediated immune response play an essential role in the pathogenesis of severe sepsis. Studies examining associations of TNF and lymphotoxin-α (LTA) single nucleotide polymorphisms (SNPs) with severe sepsis have produced conflicting results. The objective of this study was to investigate whether genetic variation in TNF, LTA, TNFRSF1A and TNFRSF1B was associated with susceptibility to or death from severe sepsis in Chinese Han population. METHODOLOGY/PRINCIPAL FINDINGS: Ten SNPs in TNF, LTA, TNFRSF1A and TNFRSF1B were genotyped in samples of patients with severe sepsis (n = 432), sepsis (n = 384) and healthy controls (n = 624). Our results showed that rs1800629, a SNP in the promoter region of TNF, was significantly associated with risk for severe sepsis. The minor allele frequency of rs1800629 was significantly higher in severe sepsis patients than that in both healthy controls (P(adj) = 0.00046, odds ratio (OR)(adj) = 1.92) and sepsis patients (P(adj) = 0.002, OR(adj) = 1.56). Further, we investigated the correlation between rs1800629 genotypes and TNF-α concentrations in peripheral blood mononuclear cells (PBMCs) of healthy volunteers exposed to lipopolysaccharides (LPS) ex vivo, and the association between rs1800629 and TNF-α serum levels in severe sepsis patients. After exposure to LPS, the TNF-α concentration in culture supernatants of PBMCs was significantly higher in the subjects with AA+AG genotypes than that with GG genotype (P = 0.007). Moreover, in patients with severe sepsis, individuals with AA+AG genotypes had significantly higher TNF-α serum concentrations than those with GG genotype (P(adj) = 0.02). However, there were no significant associations between SNPs in the four candidate genes and 30 day mortality for patients with severe sepsis. CONCLUSIONS/SIGNIFICANCE: Our findings suggested that the functional TNF gene SNP rs1800629 was strongly associated with susceptibility to severe sepsis, but not with lethality in Chinese Han population.",2012 Sep 27,"['Song, Zhenju', 'Song, Yuanlin', 'Yin, Jun', 'Shen, Yao', 'Yao, Chenling', 'Sun, Zhan', 'Jiang, Jinjun', 'Zhu, Duming', 'Zhang, Yong', 'Shen, Qinjun', 'Gao, Lei', 'Tong, Chaoyang', 'Bai, Chunxue']",PLoS One,,,True
a9e209c7a59e188267e27014ed46db5490b57543,PMC,Partial and Full PCR-Based Reverse Genetics Strategy for Influenza Viruses,http://dx.doi.org/10.1371/journal.pone.0046378,PMC3460856,23029501,CC BY,"Since 1999, plasmid-based reverse genetics (RG) systems have revolutionized the way influenza viruses are studied. However, it is not unusual to encounter cloning difficulties for one or more influenza genes while attempting to recover virus de novo. To overcome some of these shortcomings we sought to develop partial or full plasmid-free RG systems. The influenza gene of choice is assembled into a RG competent unit by virtue of overlapping PCR reactions containing a cDNA copy of the viral gene segment under the control of RNA polymerase I promoter (pol1) and termination (t1) signals – herein referred to as Flu PCR amplicons. Transfection of tissue culture cells with either HA or NA Flu PCR amplicons and 7 plasmids encoding the remaining influenza RG units, resulted in efficient virus rescue. Likewise, transfections including both HA and NA Flu PCR amplicons and 6 RG plasmids also resulted in efficient virus rescue. In addition, influenza viruses were recovered from a full set of Flu PCR amplicons without the use of plasmids.",2012 Sep 28,"['Chen, Hongjun', 'Ye, Jianqiang', 'Xu, Kemin', 'Angel, Matthew', 'Shao, Hongxia', 'Ferrero, Andrea', 'Sutton, Troy', 'Perez, Daniel R.']",PLoS One,,,True
a015401a1cdf151bd0bca060bd8eb96d6683a147,PMC,"Identification, Characterization and Application of a G-Quadruplex Structured DNA Aptamer against Cancer Biomarker Protein Anterior Gradient Homolog 2",http://dx.doi.org/10.1371/journal.pone.0046393,PMC3460915,23029506,CC BY,"BACKGROUND: Anterior gradient homolog 2 (AGR2) is a functional protein with critical roles in a diverse range of biological systems, including vertebrate tissue development, inflammatory tissue injury responses, and cancer progression. Clinical studies have shown that the AGR2 protein is overexpressed in a wide range of human cancers, including carcinomas of the esophagus, pancreas, breast, prostate, and lung, making the protein as a potential cancer biomarker. However, the general biochemical functions of AGR2 in human cells remain undefined, and the signaling mechanisms that drive AGR2 to inhibit p53 are still not clearly illustrated. Therefore, it is of great interest to develop molecular probes specifically recognizing AGR2 for its detection and for the elucidation of AGR2-associated molecular mechanism. METHODOLOGY/PRINCIPAL FINDINGS: Through a bead-based and flow cytometry monitored SELEX technology, we have identified a group of DNA aptamers that can specifically bind to AGR2 with K(d) values in the nanomolar range after 14 rounds of selections. Aptamer C14B was chosen to further study, due to its high binding affinity and specificity. The optimized and shortened C14B1 has special G-rich characteristics, and the G-rich region of this binding motif was further characterized to reveal an intramolecular parallel G-quadruplex by CD spectroscopy and UV spectroscopy. Our experiments confirmed that the stability of the G-quadruplex structure was strongly dependent on the nature of the monovalent ions and the formation of G-quadruplex structure was also important for the binding capacity of C14B1 to the target. Furthermore, we have designed a kind of allosteric molecule beacon (aMB) probe for selective and sensitive detection of AGR2. CONCLUSION/SIGNIFICANCE: In this work, we have developed new aptamer probes for specific recognition of the AGR2. Structural study have identified that the binding motif of aptamer is an intramolecular parallel G-quadruplex structure and its structure and binding affinity are strongly dependent on the nature of the monovalent ion. Furthermore, with our design of AGR2-aMB, AGR2 could be sensitively and selectively detected. This aptamer probe has great potential to serve as a useful tool for early diagnosis and prognosis of cancer and for fundamental research to elucidate the biochemical functions of AGR2.",2012 Sep 28,"['Wu, Jie', 'Wang, Chi', 'Li, Xilan', 'Song, Yanling', 'Wang, Wei', 'Li, Cong', 'Hu, Jia', 'Zhu, Zhi', 'Li, Jiuxing', 'Zhang, Weiyun', 'Lu, Zhongxian', 'Yang, Chaoyong James']",PLoS One,,,True
faada181a26e163dce05aa155b1516a66bb6154b,PMC,Airport sentinel surveillance and entry quarantine for dengue infections following a fever screening program in Taiwan,http://dx.doi.org/10.1186/1471-2334-12-182,PMC3462143,22867003,CC BY,"BACKGROUND: Dengue has not reached an endemic status in Taiwan; nevertheless, we have implemented a fever screening program at airports for the early detection of febrile passengers with a dengue infection. This study is intended to assess the performance of the airport screening procedures for dengue infection. METHODS: We analyzed data from the national surveillance system of the Taiwan Centers for Disease Control. We included the imported dengue cases reported by sentinel airports and clinics as well as the domestic cases from 2007–2010. RESULTS: Approximately 44.9% (95%CI: 35.73-54.13%) of the confirmed imported dengue cases with an apparent symptom (febrile) in the viremic stage were detected via the airport fever screening program, with an estimated positive predictive value of 2.36% (95% CI: 0.96- 3.75%) and a negative predictive value > 99.99%. Fluctuations in the number of the symptomatic imported dengue cases identified in the airports (X) were associated with the total number of imported dengue cases (Y) based on a regression analysis of a biweekly surveillance (i.e., n = 104, R(2)(X:Y) = 0.61, P < 0.005). Additionally, the fluctuating patterns in the cumulative numbers of the imported dengue cases (X) with a 1–2 month lead time (t) was in parallel with that of the domestic dengue cases (Y) based on a consecutive 4-year surveillance (i.e., n = 48, R(2)(X(t-1):Y) = 0.22, R(2)(X(t-2):Y) = 0.31, P < 0.001) from 2007–2010. CONCLUSIONS: A moderate sensitivity of detecting dengue at the airports examined in this study indicated some limitations of the fever screening program for the prevention of importation. The screening program could assist in the rapid triage for self-quarantine of some symptomatic dengue cases that were in the viremic stage at the borders and contribute to active sentinel surveillance; however, the blocking of viral transmission to susceptible populations (neighbors or family) from all of the viremic travelers, including those with or without symptoms, is critical to prevent dengue epidemics. Therefore, the reinforcement of mosquito bite prevention and household vector control in dengue-endemic or dengue-competent hotspots during an epidemic season is essential and highly recommended.",2012 Aug 6,"['Kuan, Mei-Mei', 'Chang, Feng-Yee']",BMC Infect Dis,,,True
2857cb1d4c6c446ac30ab4d0cabca0b42d62c465,PMC,The development of a GeXP-based multiplex reverse transcription-PCR assay for simultaneous detection of sixteen human respiratory virus types/subtypes,http://dx.doi.org/10.1186/1471-2334-12-189,PMC3462154,22891685,CC BY,"BACKGROUND: Existing standard non-molecular diagnostic methods such as viral culture and immunofluorescent (DFA) are time-consuming, labor intensive or limited sensitivity. Several multiplex molecular assays are costly. Therefore, there is a need for the development of a rapid and sensitive diagnosis of respiratory viral pathogens. METHODS: A GeXP-based multiplex RT-PCR assay (GeXP assay) was developed to detect simultaneously sixteen different respiratory virus types/subtypes. Seventeen sets of chimeric primers were used to initiate the RT-PCR, and one pair of universal primers was used for the subsequent cycles of the RT-PCR. The specificity of the GeXP assay was examined with positive controls for each virus type/subtype. The sensitivity was evaluated by performing the assay on serial ten-fold dilutions of in vitro-transcribed RNA of all RNA viruses and the plasmids containing the Adv and HBoV target sequence. GeXP assay was further evaluated using 126 clinical specimens and compared with Luminex xTAG RVP Fast assay. RESULTS: The GeXP assay achieved a sensitivity of 20–200 copies for a single virus and 1000 copies when all of the 16 pre-mixed viral targets were present. Analyses of 126 clinical specimens using the GeXP assay demonstrated that GeXP assay and the RVP Fast assay were in complete agreement for 109/126 (88.51%) of the specimens. GeXP assay was more sensitive than the RVP Fast assay for the detection of HRV and PIV3, and slightly less sensitive for the detection of HMPV, Adv, RSVB and HBoV. The whole process of the GeXP assay for the detection of 12 samples was completed within 2.5 hours. CONCLUSIONS: In conclusion, the GeXP assay is a rapid, cost-effective, sensitive, specific and high throughput method for the detection of respiratory virus infections.",2012 Aug 14,"['Li, Jin', 'Mao, Nai-Ying', 'Zhang, Chen', 'Yang, Meng-Jie', 'Wang, Miao', 'Xu, Wen-Bo', 'Ma, Xue-Jun']",BMC Infect Dis,,,True
a646c8ced739fd583e7e031a90e4936f2a764035,PMC,Dynamics of a Cytokine Storm,http://dx.doi.org/10.1371/journal.pone.0045027,PMC3462188,23049677,CC BY,"Six volunteers experienced severe inflammatory response during the Phase I clinical trial of a monoclonal antibody that was designed to stimulate a regulatory T cell response. Soon after the trial began, each volunteer experienced a “cytokine storm”, a dramatic increase in cytokine concentrations. The monoclonal antibody, TGN1412, raised serum concentrations of both pro- and anti-inflammatory cytokines το very hiγh values during the first day, while lymphocyte and monocyte concentrations plummeted. Because the subjects were healthy and had no prior indications of immune deficiency, this event provided an unusual opportunity to study the dynamic interactions of cytokines and other measured parameters. Here, the response histories of nine cytokines have been modeled by a set of linear ordinary differential equations. A general search procedure identifies parameters of the model, whose response fits the data well during the five-day measurement period. The eighteenth-order model reveals plausible cause-and-effect relationships among the cytokines, showing how each cytokine induces or inhibits other cytokines. It suggests that perturbations in IL2, IL8, and IL10 have the most significant inductive effect, while IFN-γ and IL12 have the greatest inhibiting effect on other cytokine concentrations. Although TNF-α is a major pro-inflammatory factor, IFN-γ and three other cytokines have faster initial and median response to TGN1412 infusion. Principal-component analysis of the data reveals three clusters of similar cytokine responses: [TNF-α, IL1, IL10], [IFN-γ, IL2, IL4, IL8, and IL12], and [IL6]. IL1, IL6, IL10, and TNF-α have the highest degree of variability in response to uncertain initial conditions, exogenous effects, and parameter estimates. This study illuminates details of a cytokine storm event, and it demonstrates the value of linear modeling for interpreting complex, coupled biological system dynamics from empirical data.",2012 Oct 1,"['Yiu, Hao Hong', 'Graham, Andrea L.', 'Stengel, Robert F.']",PLoS One,,,True
6cabb3c8d1e85384320c6d9f7c927f4abc93fd93,PMC,Flt3L Combined with Rapamycin Promotes Cardiac Allograft Tolerance by Inducing Regulatory Dendritic Cells and Allograft Autophagy in Mice,http://dx.doi.org/10.1371/journal.pone.0046230,PMC3462742,23056267,CC BY,"The induction of immune tolerance is still a formidable challenge in organ transplantation. Dendritic cells (DCs) play an important role in orchestrating immune responses by either mediating protective immune responses or inducing antigen specific tolerance. Previous studies demonstrated that the fms-like tyrosine kinase 3 receptor (Flt3) and its ligand (Flt3L) play an essential role in the regulation of DC commitment and development. Here, we report a synergic effect between Flt3L and low-dose rapamycin (Rapa) in the protection of allograft rejction. It was found that Flt3L combined with Rapa significantly prolonged murine cardiac allograft survival time as compared with that of untreated recipients or recipients treated with Rapa or Flt3L alone. Mechanistic studies revealed that Flt3L combined with low-dose of Rapa induced the generation of tolerogenic DCs along with the production of CD25(+) Foxp3(+) regulatory T cells and IL-10 secretion. We also observed enhanced autophagy in the cardiac allograft, which could be another asset contributing to the enhanced allograft survival. All together, these data suggest that Flt3L combined with low-dose of Rapa could be an effective therapeutic approach to induce tolerance in clinical setting of transplantation.",2012 Oct 2,"['Xiong, Ali', 'Duan, Lihua', 'Chen, Jie', 'Fan, Zhigang', 'Zheng, Fang', 'Tan, Zheng', 'Gong, Feili', 'Fang, Min']",PLoS One,,,True
04a253fd34bd82b3cf7868fca967469c66e392ab,PMC,RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response,http://dx.doi.org/10.1371/journal.pone.0042583,PMC3463586,23056170,CC BY,"Recognition of virus infection by innate pattern recognition receptors (PRRs), including membrane-associated toll-like receptors (TLR) and cytoplasmic RIG-I-like receptors (RLR), activates cascades of signal transduction pathways leading to production of type I interferons (IFN) and proinflammatory cytokines that orchestrate the elimination of the viruses. Although it has been demonstrated that PRR-mediated innate immunity plays an essential role in defending virus from infection, it also occasionally results in overwhelming production of proinflammatory cytokines that cause severe inflammation, blood vessel leakage and tissue damage. In our efforts to identify small molecules that selectively enhance PRR-mediated antiviral, but not the detrimental inflammatory response, we discovered a compound, RO 90–7501 (‘2’-(4-Aminophenyl)-[2,5′-bi-1H-benzimidazol]-5-amine), that significantly promoted both TLR3 and RLR ligand-induced IFN-β gene expression and antiviral response, most likely via selective activation of p38 mitogen-activated protein kinase (MAPK) pathway. Our results thus imply that pharmacological modulation of PRR signal transduction pathways in favor of the induction of a beneficial antiviral response can be a novel therapeutic strategy.",2012 Oct 3,"['Guo, Fang', 'Mead, Jennifer', 'Aliya, Nishat', 'Wang, Lijuan', 'Cuconati, Andrea', 'Wei, Lai', 'Li, Kui', 'Block, Timothy M.', 'Guo, Ju-Tao', 'Chang, Jinhong']",PLoS One,,,True
628b63978a499c7cdecbccf06dd60980da895fb0,PMC,Renalase's Expression and Distribution in Renal Tissue and Cells,http://dx.doi.org/10.1371/journal.pone.0046442,PMC3463591,23056310,CC BY,"To study renalase's expression and distribution in renal tissues and cells, renalase coded DNA vaccine was constructed, and anti-renalase monoclonal antibodies were produced using DNA immunization and hybridoma technique, followed by further investigation with immunological testing and western blotting to detect the expression and distribution of renalase among the renal tissue and cells. Anti-renalase monoclonal antibodies were successfully prepared by using DNA immunization technique. Further studies with anti-renalase monoclonal antibody showed that renalase expressed in glomeruli, tubule, mesangial cells, podocytes, renal tubule epithelial cells and its cells supernatant. Renalase is wildly expressed in kidney, including glomeruli, tubule, mesangial cells, podocytes and tubule epithelial cells, and may be secreted by tubule epithelial cells primarily.",2012 Oct 3,"['Wang, Feng', 'Xing, Tao', 'Li, Junhui', 'Bai, Mei', 'Hu, Ruimin', 'Zhao, Zhonghua', 'Tian, Shoufu', 'Zhang, Zhigang', 'Wang, Niansong']",PLoS One,,,True
03b9acce84a4799d4be1152a36abfaf52fb3b523,PMC,Representative Contact Diaries for Modeling the Spread of Infectious Diseases in Taiwan,http://dx.doi.org/10.1371/journal.pone.0045113,PMC3463600,23056193,CC BY,"Recent studies of infectious diseases have attempted to construct more realistic parameters of interpersonal contact patterns from diary-approach surveys. To ensure that such diary-based contact patterns provide accurate baseline data for policy implementation in densely populated Taiwan, we collected contact diaries from a national sample, using 3-stage systematic probability sampling and rigorous in-person interviews. A representative sample of 1,943 contact diaries recorded a total of 24,265 wide-range, face-to-face interpersonal contacts during a 24-hour period. Nearly 70% of the contacts occurred outside of respondents' households. The most active age group was schoolchildren (ages 5–14), who averaged around 16–18 daily contacts, about 2–3 times as many as the least active age groups. We show how such parameters of contact patterns help modify a sophisticated national simulation system that has been used for years to model the spread of pandemic diseases in Taiwan. Based on such actual and representative data that enable researchers to infer findings to the whole population, our analyses aim to facilitate implementing more appropriate and effective strategies for controlling an emerging or pandemic disease infection.",2012 Oct 3,"['Fu, Yang-chih', 'Wang, Da-Wei', 'Chuang, Jen-Hsiang']",PLoS One,,,True
4501afb17c42f81f10cefa7c72ef331c15f61fb9,PMC,DENV Inhibits Type I IFN Production in Infected Cells by Cleaving Human STING,http://dx.doi.org/10.1371/journal.ppat.1002934,PMC3464218,23055924,CC BY,"Dengue virus (DENV) is a pathogen with a high impact on human health. It replicates in a wide range of cells involved in the immune response. To efficiently infect humans, DENV must evade or inhibit fundamental elements of the innate immune system, namely the type I interferon response. DENV circumvents the host immune response by expressing proteins that antagonize the cellular innate immunity. We have recently documented the inhibition of type I IFN production by the proteolytic activity of DENV NS2B3 protease complex in human monocyte derived dendritic cells (MDDCs). In the present report we identify the human adaptor molecule STING as a target of the NS2B3 protease complex. We characterize the mechanism of inhibition of type I IFN production in primary human MDDCs by this viral factor. Using different human and mouse primary cells lacking STING, we show enhanced DENV replication. Conversely, mutated versions of STING that cannot be cleaved by the DENV NS2B3 protease induced higher levels of type I IFN after infection with DENV. Additionally, we show that DENV NS2B3 is not able to degrade the mouse version of STING, a phenomenon that severely restricts the replication of DENV in mouse cells, suggesting that STING plays a key role in the inhibition of DENV infection and spread in mice.",2012 Oct 4,"['Aguirre, Sebastian', 'Maestre, Ana M.', 'Pagni, Sarah', 'Patel, Jenish R.', 'Savage, Timothy', 'Gutman, Delia', 'Maringer, Kevin', 'Bernal-Rubio, Dabeiba', 'Shabman, Reed S.', 'Simon, Viviana', 'Rodriguez-Madoz, Juan R.', 'Mulder, Lubbertus C. F.', 'Barber, Glen N.', 'Fernandez-Sesma, Ana']",PLoS Pathog,,,True
3c83a45d3f3e227de8b5e0e88022352385dd78e8,PMC,Impact of drug price adjustments on utilization of and expenditures on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in Taiwan,http://dx.doi.org/10.1186/1471-2458-12-288,PMC3464938,22521158,CC BY,"BACKGROUND: A previous study has suggested that drug price adjustments allow physicians in Taiwan to gain greater profit by prescribing generic drugs. To better understand the effect of price adjustments on physician choice, this study used renin-angiotensin drugs (including angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) to examine the impact of price adjustments on utilization of and expenditures on patented and off-patent drugs with the same therapeutic indication. METHODS: Using the Taiwan’s Longitudinal Health Insurance Database (2005), we identified 147,157 patients received ACEIs and/or ARBs between 1997 and 2008. The annual incident and prevalent users of ACEIs, ARBs and overall renin-angiotensin drugs were examined. Box-Tiao intervention analysis was applied to assess the impact of price adjustments on monthly utilization of and expenditures on these drugs. ACEIs were divided into patented and off-patent drugs, off-patent ACEIs were further divided into original brands and generics, and subgroup analyses were performed. RESULTS: The number of incident renin-angiotensin drug users decreased over the study period. The number of prevalent ARB users increased and exceeded the cumulative number of first-time renin-angiotensin drug users starting on ARBs, implying that some patients switched from ACEIs to ARBs. After price adjustments, long term trend increases in utilization were observed for patented ACEIs and ARBs; a long-term trend decrease was observed for off-patent ACEIs; long-term trend change was not significant for overall renin-angiotensin drugs. Significant long-term trend increases in expenditures were observed for patented ACEIs after price adjustment in 2007 (200.9%, p = 0.0088) and in ARBs after price adjustments in 2001 (173.4%, p < 0.0001) and 2007 (146.3%, p < 0.0001). A significant long-term trend decrease in expenditures was observed for off-patent ACEIs after 2004 price adjustment (−156.9%, p < 0.0001). Expenditures on overall renin-angiotensin drugs showed long-term trend increases after price adjustments in 2001 (72.2%, p < 0.0001) and 2007 (133.4%, p < 0.0001). CONCLUSIONS: Price adjustments did not achieve long-term cost savings for overall renin-angiotensin drugs. Possible switching from ACEIs to ARBs within individuals is evident. Policy makers should reconsider the appropriateness of the current adjustment strategies applied to patented and off-patent drugs.",2012 Apr 20,"['Huang, Shiou-Huei', 'Hsu, Chien-Ning', 'Yu, Shu-Hui', 'Cham, Thau-Ming']",BMC Public Health,,,True
5ee02e510d7fb0b2523b669dacadf4f56ee6b55f,PMC,Impact of drug price adjustments on utilization of and expenditures on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in Taiwan,http://dx.doi.org/10.1186/1471-2458-12-288,PMC3464938,22521158,CC BY,"BACKGROUND: A previous study has suggested that drug price adjustments allow physicians in Taiwan to gain greater profit by prescribing generic drugs. To better understand the effect of price adjustments on physician choice, this study used renin-angiotensin drugs (including angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) to examine the impact of price adjustments on utilization of and expenditures on patented and off-patent drugs with the same therapeutic indication. METHODS: Using the Taiwan’s Longitudinal Health Insurance Database (2005), we identified 147,157 patients received ACEIs and/or ARBs between 1997 and 2008. The annual incident and prevalent users of ACEIs, ARBs and overall renin-angiotensin drugs were examined. Box-Tiao intervention analysis was applied to assess the impact of price adjustments on monthly utilization of and expenditures on these drugs. ACEIs were divided into patented and off-patent drugs, off-patent ACEIs were further divided into original brands and generics, and subgroup analyses were performed. RESULTS: The number of incident renin-angiotensin drug users decreased over the study period. The number of prevalent ARB users increased and exceeded the cumulative number of first-time renin-angiotensin drug users starting on ARBs, implying that some patients switched from ACEIs to ARBs. After price adjustments, long term trend increases in utilization were observed for patented ACEIs and ARBs; a long-term trend decrease was observed for off-patent ACEIs; long-term trend change was not significant for overall renin-angiotensin drugs. Significant long-term trend increases in expenditures were observed for patented ACEIs after price adjustment in 2007 (200.9%, p = 0.0088) and in ARBs after price adjustments in 2001 (173.4%, p < 0.0001) and 2007 (146.3%, p < 0.0001). A significant long-term trend decrease in expenditures was observed for off-patent ACEIs after 2004 price adjustment (−156.9%, p < 0.0001). Expenditures on overall renin-angiotensin drugs showed long-term trend increases after price adjustments in 2001 (72.2%, p < 0.0001) and 2007 (133.4%, p < 0.0001). CONCLUSIONS: Price adjustments did not achieve long-term cost savings for overall renin-angiotensin drugs. Possible switching from ACEIs to ARBs within individuals is evident. Policy makers should reconsider the appropriateness of the current adjustment strategies applied to patented and off-patent drugs.",2012 Apr 20,"['Huang, Shiou-Huei', 'Hsu, Chien-Ning', 'Yu, Shu-Hui', 'Cham, Thau-Ming']",BMC Public Health,,,True
03d7c96afa37141562c3ac9297882dbe59d2e0e4,PMC,Simultaneous investigation of influenza and enteric viruses in the stools of adult patients consulting in general practice for acute diarrhea,http://dx.doi.org/10.1186/1743-422X-9-116,PMC3466123,22709374,CC BY,"BACKGROUND: Gastrointestinal symptoms are not an uncommon manifestation of an influenza virus infection. In the present study, we aimed to investigate the presence of influenza viruses in the stools of adult patients consulting their general practitioner for uncomplicated acute diarrhea (AD) and the proportion of concurrent infections by enteric and influenza viruses. METHOD: A case-control study was conducted from December 2010 to April 2011. Stool specimens were collected and tested for influenza viruses A (seasonal A/H3N2 and pandemic A/H1N1) and B, and for four enteric viruses (astrovirus, group A rotavirus, human enteric adenovirus, norovirus of genogroups I – NoVGI - and genogroup II - NoVGII). RESULTS: General practitioners enrolled 138 cases and 93 controls. Of the 138 stool specimens collected, 92 (66.7%) were positive for at least one of the four enteric viruses analysed and 10 (7.2%) tested positive for one influenza virus. None of these 10 influenza positive patients reported respiratory symptoms. In five influenza-positive patients (3.6%), we also detected one enteric virus, with 4 of them being positive for influenza B (2 had co-detection with NoVGI, 1 with NoVGII, and 1 with astrovirus). None of the 93 controls tested positive for one of the enteric and/or other influenza viruses we investigated. CONCLUSIONS: In this study we showed that the simultaneous detection of influenza and enteric viruses is not a rare event. We have also reported, for the first time in general practice, the presence of seasonal and pandemic influenza viruses in the stools of adult patients consulting for uncomplicated AD. A simultaneous investigation of enteric and influenza viruses in patients complaining of gastrointestinal symptoms could be useful for future studies to better identify the agents responsible for AD.",2012 Jun 18,"['Arena, Christophe', 'Amoros, Jean Pierre', 'Vaillant, Véronique', 'Balay, Katia', 'Chikhi-Brachet, Roxane', 'Varesi, Laurent', 'Arrighi, Jean', 'Blanchon, Thierry', 'Carrat, Fabrice', 'Hanslik, Thomas', 'Falchi, Alessandra']",Virol J,,,True
6135c4bb442a034b18ef4e9b3fc5701507225f0d,PMC,Acute Reactogenicity after Intramuscular Immunization with Recombinant Vesicular Stomatitis Virus Is Linked to Production of IL-1β,http://dx.doi.org/10.1371/journal.pone.0046516,PMC3466325,23056330,CC BY,"Vaccines based on live viruses are attractive because they are immunogenic, cost-effective, and can be delivered by multiple routes. However, live virus vaccines also cause reactogenic side effects such as fever, myalgia, and injection site pain that have reduced their acceptance in the clinic. Several recent studies have linked vaccine-induced reactogenic side effects to production of the pro-inflammatory cytokine interleukin-1β (IL-1β) in humans. Our objective was therefore to determine whether IL-1β contributed to pathology after immunization with recombinant vesicular stomatitis virus (rVSV) vaccine vectors, and if so, to identify strategies by which IL-1β mediated pathology might be reduced without compromising immunogenicity. We found that an rVSV vaccine induced local and systemic production of IL-1β in vivo, and that accumulation of IL-1β correlated with acute pathology after rVSV immunization. rVSV-induced pathology was reduced in mice deficient in the IL-1 receptor Type I, but the IL-1R−/− mice were fully protected from lethal rechallenge with a high dose of VSV. This result demonstrated that IL-1 contributed to reactogenicity of the rVSV, but was dispensable for induction of protective immunity. The amount of IL-1β detected in mice deficient in either caspase-1 or the inflammasome adaptor molecule ASC after rVSV immunization was not significantly different than that produced by wild type animals, and caspase-1−/− and ASC−/− mice were only partially protected from rVSV-induced pathology. Those data support the idea that some of the IL-1β expressed in vivo in response to VSV may be activated by a caspase-1 and ASC-independent mechanism. Together these results suggest that rVSV vectors engineered to suppress the induction of IL-1β, or signaling through the IL-1R would be less reactogenic in vivo, but would retain their immunogenicity and protective capacity. Such rVSV would be highly desirable as either vaccine vectors or oncolytic therapies, and would likely be better tolerated in human vaccinees.",2012 Oct 8,"['Athearn, Kathleen', 'Sample, Christopher J.', 'Barefoot, Brice E.', 'Williams, Kristi L.', 'Ramsburg, Elizabeth A.']",PLoS One,,,True
d672ce4063b2033261865d54cc7db91b9186beee,PMC,Oroxylin-A Rescues LPS-Induced Acute Lung Injury via Regulation of NF-κB Signaling Pathway in Rodents,http://dx.doi.org/10.1371/journal.pone.0047403,PMC3468516,23071799,CC BY,"BACKGROUND AND PURPOSE: Successful drug treatment for sepsis-related acute lung injury (ALI) remains a major clinical problem. This study was designed to assess the beneficial effects of post-treatment of oroxylin A (OroA), a flavonoid, in ameliorating lipopolysaccharides (LPS)-induced lung inflammation and fatality. EXPERIMENTAL APPROACH: Rats were injected with LPS (10 mg/kg, iv) to induce ALI, and OroA was given (15 mg/kg, iv) 1 hr or 6 hrs after LPS challenge. Twenty four hrs after LPS challenge, biochemical changes in the blood and lung tissues, and morphological/histological alterations in the lung associated with inflammation and injury were examined. Therapeutic effect of OroA was assessed by measuring the survival rate in endotoxemic mice. KEY RESULTS: LPS (10 mg/kg, iv) significantly altered WBC counts, elevated plasma tumor necrosis factor (TNF)-α and nitric oxide (NO), increased pulmonary edema, thickened alveolar septa, and decreased survival rate. These changes were ameliorated by OroA (15 mg/kg, iv) administered 1 hr or 6 hrs after LPS challenge. This post-treatment also significantly attenuated LPS-induced activation of nuclear factor-κB (NF-κB) and the release of high mobility group box 1 (HMGB1) in lung tissues. Furthermore, post-treatment with OroA (60 mg/kg, ip) administered 1 hr or 6 hrs after LPS challenge in mice significantly increased survival rate. CONCLUSION AND IMPLICATION: OroA administered after induction of ALI by LPS significantly prevent and revere lung tissues injuries with increased survival rate. Positive post-treatment effects of OroA suggest that OroA is a potentially useful candidate for managing lung inflammation in LPS-induced endotoxemia and septic shock.",2012 Oct 10,"['Tseng, Tzu-Ling', 'Chen, Mei-Fang', 'Tsai, Ming-Jen', 'Hsu, Yung-Hsiang', 'Chen, Chin-Piao', 'Lee, Tony J. F.']",PLoS One,,,True
2431c74630bb92f71e47e7f1c89054cef368ace0,PMC,"Introducing Alphitobius diaperinus, (Insecta: Tenebrionidae) as a New Intermediate Host of Hadjelia truncata (Nematoda)",,PMC3469194,23109952,CC BY,"BACKGROUND: Hadjelia truncata is a nematode that causes lesions in the gizzard lining of pigeons, which may even lead to death. The aim of this study was to introduce Alphitobius diaperinus as a new intermediate host for Hadjelia truncata. METHODS: H. truncata infection was identified in a pigeon flock in Ahvaz City, Khuzestan Province, Iran by performing fecal examination and autopsy. Adult and larval stages of beetles were collected from the litter of pigeon houses, and identified morphologically. The beetle larvae were cultured in a medium, containing feces of the infected pigeons. Nematode larval stages from naturally and experimentally (culturally) infected adult beetles were fed to two groups of pigeons RESULTS: The collected beetles were identified as Alphitobius diaperinus. Average length and width of the adult beetles were 6.31 mm and 2.88 mm respectively. Infection rates of naturally and experimentally infected beetles with larval stages of the nematode were 66.2% and 45.1% respectively. The adult nematodes collected from gizzards of experimentally infected pigeons were identified as H. truncata. Nematode infection rates in pigeons after feeding the infective larvae collected from naturally and experimentally infected beetles were 44.7% and 32.5% respectively. CONCLUSION: A. diaperinus can serve as a natural intermediate host for H. truncata.",2012,"['Alborzi, AR', 'Rahbar, A']",Iran J Parasitol,,,True
bf4d08eb7675759c77b722b7509bea52906930da,PMC,Competition between Influenza A Virus Genome Segments,http://dx.doi.org/10.1371/journal.pone.0047529,PMC3469491,23071819,CC BY,"Influenza A virus (IAV) contains a segmented negative-strand RNA genome. How IAV balances the replication and transcription of its multiple genome segments is not understood. We developed a dual competition assay based on the co-transfection of firefly or Gaussia luciferase-encoding genome segments together with plasmids encoding IAV polymerase subunits and nucleoprotein. At limiting amounts of polymerase subunits, expression of the firefly luciferase segment was negatively affected by the presence of its Gaussia luciferase counterpart, indicative of competition between reporter genome segments. This competition could be relieved by increasing or decreasing the relative amounts of firefly or Gaussia reporter segment, respectively. The balance between the luciferase expression levels was also affected by the identity of the untranslated regions (UTRs) as well as segment length. In general it appeared that genome segments displaying inherent higher expression levels were more efficient competitors of another segment. When natural genome segments were tested for their ability to suppress reporter gene expression, shorter genome segments generally reduced firefly luciferase expression to a larger extent, with the M and NS segments having the largest effect. The balance between different reporter segments was most dramatically affected by the introduction of UTR panhandle-stabilizing mutations. Furthermore, only reporter genome segments carrying these mutations were able to efficiently compete with the natural genome segments in infected cells. Our data indicate that IAV genome segments compete for available polymerases. Competition is affected by segment length, coding region, and UTRs. This competition is probably most apparent early during infection, when limiting amounts of polymerases are present, and may contribute to the regulation of segment-specific replication and transcription.",2012 Oct 11,"['Widjaja, Ivy', 'de Vries, Erik', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.']",PLoS One,,,True
e57993034cb1196b96daff4505db38640782f4a0,PMC,An Analysis of Regulatory T-Cell and Th-17 Cell Dynamics during Cytomegalovirus Replication in Solid Organ Transplant Recipients,http://dx.doi.org/10.1371/journal.pone.0043937,PMC3469568,23071829,CC BY,"BACKGROUND: CMV-specific T-cells are crucial to control CMV-replication post-transplant. Regulatory T-cells (T-regs) are associated with a tolerant immune state and may contribute to CMV-replication. However, T-cell subsets such as T-regs and IL-17 producing T-cells (Th-17) are not well studied in this context. We explored T-regs and Th-17 frequencies during CMV-replication after transplantation. METHODS: We prospectively evaluated 30 transplant patients with CMV-viremia. We quantified CMV-specific CD4(+) and CD8(+) T-cells, T-regs (CD4(+)CD25(+)FoxP3(+)) and Th-17 frequencies using flow-cytometry and followed patients requiring anti-viral treatment. Two subsets were compared: anti-viral treatment requirement (n = 20) vs. spontaneous clearance of viremia (n = 10). RESULTS: Higher initial CMV-specific CD4(+) T-cells and lower T-regs were observed in patients with spontaneous clearance (p = 0.043; p = 0.021 respectively). Using a ratio of CMV-specific CD4(+) T-cells to T-regs allowed prediction of viral clearance with 80% sensitivity and 90% specificity (p = 0.001). One month after stop of treatment, the same correlation was observed in patients protected from CMV-relapse. The ratio of CMV-specific CD4(+) T-cells to T-regs allowed prediction of relapse with 85% sensitivity and 86% specificity (p = 0.004). Th-17 responses were not correlated with virologic outcomes. CONCLUSIONS: This study provides novel insights into T-regs and Th-17 subpopulations during CMV-replication after transplantation. These preliminary data suggest that measurement of CMV-specific CD4(+) T-cells together with T-regs has value in predicting spontaneous clearance of viremia and relapse.",2012 Oct 11,"['Egli, Adrian', 'Silva, Moacyr', ""O'Shea, Daire"", 'Wilson, Leticia E.', 'Baluch, Aliyah', 'Lisboa, Luiz F.', 'Hidalgo, Luis G.', 'Kumar, Deepali', 'Humar, Atul']",PLoS One,,,True
bbc2824ce7dff3d23d060b7abbe96cba28095fb8,PMC,Respiratory viral infections in children with asthma: do they matter and can we prevent them?,http://dx.doi.org/10.1186/1471-2431-12-147,PMC3471019,22974166,CC BY,"BACKGROUND: Asthma is a major public health problem with a huge social and economic burden affecting 300 million people worldwide. Viral respiratory infections are the major cause of acute asthma exacerbations and may contribute to asthma inception in high risk young children with susceptible genetic background. Acute exacerbations are associated with decreased lung growth or accelerated loss of lung function and, as such, add substantially to both the cost and morbidity associated with asthma. DISCUSSION: While the importance of preventing viral infection is well established, preventive strategies have not been well explored. Good personal hygiene, hand-washing and avoidance of cigarette smoke are likely to reduce respiratory viral infections. Eating a healthy balanced diet, active probiotic supplements and bacterial-derived products, such as OM-85, may reduce recurrent infections in susceptible children. There are no practical anti-viral therapies currently available that are suitable for widespread use. SUMMARY: Hand hygiene is the best measure to prevent the common cold. A healthy balanced diet, active probiotic supplements and immunostimulant OM-85 may reduce recurrent infections in asthmatic children.",2012 Sep 13,"['Ahanchian, Hamid', 'Jones, Carmen M', 'Chen, Yueh-sheng', 'Sly, Peter D']",BMC Pediatr,,,True
e4dedf2b46618a544180539e2a2943c3618b8fec,PMC,Label-Free Electrochemical Diagnosis of Viral Antigens with Genetically Engineered Fusion Protein,http://dx.doi.org/10.3390/s120810097,PMC3472818,23112590,CC BY,"We have developed a simple electrochemical biosensing strategy for the label-free diagnosis of hepatitis B virus (HBV) on a gold electrode surface. Gold-binding polypeptide (GBP) fused with single-chain antibody (ScFv) against HBV surface antigen (HBsAg), in forms of genetically engineered protein, was utilized. This GBP-ScFv fusion protein can directly bind onto the gold substrate with the strong binding affinity between the GBP and the gold surface, while the recognition site orients toward the sample for target binding at the same time. Furthermore, this one-step immobilization strategy greatly simplifies a fabrication process without any chemical modification as well as maintaining activity of biological recognition elements. This system allows specific immobilization of proteins and sensitive detection of targets, which were verified by surface plasmon resonance analysis and successfully applied to electrochemical cyclic voltammetry and impedance spectroscopy upto 0.14 ng/mL HBsAg.",2012 Jul 26,"['Heo, Nam Su', 'Zheng, Shun', 'Yang, MinHo', 'Lee, Seok Jae', 'Lee, Sang Yup', 'Kim, Hwa-Jung', 'Park, Jung Youn', 'Lee, Chang-Soo', 'Park, Tae Jung']",Sensors (Basel),,,True
cf96fbb3db5c01498ecd4d4a48a09f395e038343,PMC,Label-Free Electrochemical Diagnosis of Viral Antigens with Genetically Engineered Fusion Protein,http://dx.doi.org/10.3390/s120810097,PMC3472818,23112590,CC BY,"We have developed a simple electrochemical biosensing strategy for the label-free diagnosis of hepatitis B virus (HBV) on a gold electrode surface. Gold-binding polypeptide (GBP) fused with single-chain antibody (ScFv) against HBV surface antigen (HBsAg), in forms of genetically engineered protein, was utilized. This GBP-ScFv fusion protein can directly bind onto the gold substrate with the strong binding affinity between the GBP and the gold surface, while the recognition site orients toward the sample for target binding at the same time. Furthermore, this one-step immobilization strategy greatly simplifies a fabrication process without any chemical modification as well as maintaining activity of biological recognition elements. This system allows specific immobilization of proteins and sensitive detection of targets, which were verified by surface plasmon resonance analysis and successfully applied to electrochemical cyclic voltammetry and impedance spectroscopy upto 0.14 ng/mL HBsAg.",2012 Jul 26,"['Heo, Nam Su', 'Zheng, Shun', 'Yang, MinHo', 'Lee, Seok Jae', 'Lee, Sang Yup', 'Kim, Hwa-Jung', 'Park, Jung Youn', 'Lee, Chang-Soo', 'Park, Tae Jung']",Sensors (Basel),,,False
a4ac0a556416712bc053f001c5bc6931c908bfd1,PMC,Development of a Plastic-Based Microfluidic Immunosensor Chip for Detection of H1N1 Influenza,http://dx.doi.org/10.3390/s120810810,PMC3472858,23112630,CC BY,"Lab-on-a-chip can provide convenient and accurate diagnosis tools. In this paper, a plastic-based microfluidic immunosensor chip for the diagnosis of swine flu (H1N1) was developed by immobilizing hemagglutinin antigen on a gold surface using a genetically engineered polypeptide. A fluorescent dye-labeled antibody (Ab) was used for quantifying the concentration of Ab in the immunosensor chip using a fluorescent technique. For increasing the detection efficiency and reducing the errors, three chambers and three microchannels were designed in one microfluidic chip. This protocol could be applied to the diagnosis of other infectious diseases in a microfluidic device.",2012 Aug 6,"['Lee, Kyoung G.', 'Lee, Tae Jae', 'Jeong, Soon Woo', 'Choi, Ho Woon', 'Heo, Nam Su', 'Park, Jung Youn', 'Park, Tae Jung', 'Lee, Seok Jae']",Sensors (Basel),,,True
75396899537915606b74f2b600478ad066f9d594,PMC,Hepatitis C VLPs Delivered to Dendritic Cells by a TLR2 Targeting Lipopeptide Results in Enhanced Antibody and Cell-Mediated Responses,http://dx.doi.org/10.1371/journal.pone.0047492,PMC3472981,23091628,CC BY,"Although many studies provide strong evidence supporting the development of HCV virus-like particle (VLP)-based vaccines, the fact that heterologous viral vectors and/or multiple dosing regimes are required to induce protective immunity indicates that it is necessary to improve their immunogenicity. In this study, we have evaluated the use of an anionic self-adjuvanting lipopeptide containing the TLR2 agonist Pam(2)Cys (E(8)Pam(2)Cys) to enhance the immunogenicity of VLPs containing the HCV structural proteins (core, E1 and E2) of genotype 1a. While co-formulation of this lipopeptide with VLPs only resulted in marginal improvements in dendritic cell (DC) uptake, its ability to concomitantly induce DC maturation at very small doses is a feature not observed using VLPs alone or in the presence of an aluminium hydroxide-based adjuvant (Alum). Dramatically improved VLP and E2-specific antibody responses were observed in VLP+E(8)Pam(2)Cys vaccinated mice where up to 3 doses of non-adjuvanted or traditionally alum-adjuvanted VLPs was required to match the antibody titres obtained with a single dose of VLPs formulated with this lipopeptide. This result also correlated with significantly higher numbers of specific antibody secreting cells that was detected in the spleens of VLP+E(8)Pam(2)Cys vaccinated mice and greater ability of sera from these mice to neutralise the binding and uptake of VLPs by Huh7 cells. Moreover, vaccination of HLA-A2 transgenic mice with this formulation also induced better VLP-specific IFN-γ-mediated responses compared to non-adjuvanted VLPs but comparable levels to that achieved when coadministered with complete freund’s adjuvant. These results suggest overall that the immunogenicity of HCV VLPs can be significantly improved by the addition of this novel adjuvant by targeting their delivery to DCs and could therefore constitute a viable vaccine strategy for the treatment of HCV.",2012 Oct 16,"['Chua, Brendon Y.', 'Johnson, Douglas', 'Tan, Amabel', 'Earnest-Silveira, Linda', 'Sekiya, Toshiki', 'Chin, Ruth', 'Torresi, Joseph', 'Jackson, David C.']",PLoS One,,,True
96782ada9704aca0076d39f6e2592c521d8a5383,PMC,Both STING and MAVS Fish Orthologs Contribute to the Induction of Interferon Mediated by RIG-I,http://dx.doi.org/10.1371/journal.pone.0047737,PMC3473018,23091644,CC BY,"Viral infections are detected in most cases by the host innate immune system through pattern-recognition receptors (PRR), the sensors for pathogen-associated molecular patterns (PAMPs), which induce the production of cytokines, such as type I interferons (IFN). Recent identification in mammalian and teleost fish of cytoplasmic viral RNA sensors, RIG-I-like receptors (RLRs), and their mitochondrial adaptor: the mitochondrial antiviral signaling (MAVS) protein, also called IPS-1, highlight their important role in the induction of IFN at the early stage of a virus infection. More recently, an endoplasmic reticulum (ER) adaptor: the stimulator of interferon genes (STING) protein, also called MITA, ERIS and MPYS, has been shown to play a pivotal role in response to both non-self-cytosolic RNA and dsDNA. In this study, we cloned STING cDNAs from zebrafish and showed that it was an ortholog to mammalian STING. We demonstrated that overexpression of this ER protein in fish cells led to a constitutive induction of IFN and interferon-stimulated genes (ISGs). STING-overexpressing cells were almost fully protected against RNA virus infection with a strong inhibition of both DNA and RNA virus replication. In addition, we found that together with MAVS, STING was an important player in the RIG-I IFN-inducing pathway. This report provides the demonstration that teleost fish possess a functional RLR pathway in which MAVS and STING are downstream signaling molecules of RIG-I. The Sequences presented in this article have been submitted to GenBank under accession numbers: Zebrafish STING (HE856619); EPC STING (HE856620); EPC IRF3 (HE856621); EPC IFN promoter (HE856618).",2012 Oct 16,"['Biacchesi, Stéphane', 'Mérour, Emilie', 'Lamoureux, Annie', 'Bernard, Julie', 'Brémont, Michel']",PLoS One,,,True
1952a38871ef31c0e837ff0ee666bd0350c8b32c,PMC,Infectious diseases in healthcare workers – an analysis of the standardised data set of a German compensation board,http://dx.doi.org/10.1186/1745-6673-7-8,PMC3474162,22553942,CC BY,"INTRODUCTION: Healthcare workers (HCW) are exposed to infectious agents. Disease surveillance is therefore needed in order to foster prevention. METHODS: The data of the compensation board that covers HCWs of non-governmental healthcare providers in Germany was analysed for a five-year period. For hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, the period analysed was extended to the last 15 years. The annual rate of occupational infectious diseases (OIDs) per 100,000 employees was calculated. For needlestick injuries (NSI) a rate per 1,000 employees was calculated. RESULTS: Within the five years from 2005 to 2009 a total of 384 HCV infections were recognised as OIDs (1.5/100,000 employees). Active TB was the second most frequent cause of an OID. While the numbers of HBV and HCV infections decreased, the numbers for active TB did not follow a clear pattern. Needlestick injuries (NSIs) were reported especially often at hospitals (29.9/1,000 versus 7.4/1,000 employees for all other HCWs). CONCLUSION: Although they are declining, HCV infections remain frequent in HCWs, as do NSIs. Whether the reinforcement of the recommendations for the use of safety devices in Germany will prevent NSIs and therefore HCV infections should be closely observed.",2012 May 3,"['Nienhaus, Albert', 'Kesavachandran, Chandrasekharan', 'Wendeler, Dana', 'Haamann, Frank', 'Dulon, Madeleine']",J Occup Med Toxicol,,,True
7bf54447fa81cd0f3c36e6e6455e80241fe82b0a,PMC,Associations between Pathogens in the Upper Respiratory Tract of Young Children: Interplay between Viruses and Bacteria,http://dx.doi.org/10.1371/journal.pone.0047711,PMC3474735,23082199,CC BY,"BACKGROUND: High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children. Investigating presence of and associations between these pathogens in healthy individuals is still a rather unexplored field of research, but may have implications for interpreting findings during disease. METHODOLOGY/PRINCIPAL FINDINGS: We selected 986 nasopharyngeal samples from 433 6- to 24-month-old healthy children that had participated in a randomized controlled trial. We determined the presence of 20 common respiratory viruses using real-time PCR. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus were identified by conventional culture methods. Information on risk factors was obtained by questionnaires. We performed multivariate logistic regression analyses followed by partial correlation analysis to identify the overall pattern of associations. S. pneumoniae colonization was positively associated with the presence of H. influenzae (adjusted odds ratio 1.60, 95% confidence interval 1.18–2.16), M. catarrhalis (1.78, 1.29–2.47), human rhinoviruses (1.63, 1.19–2.22) and enteroviruses (1.97, 1.26–3.10), and negatively associated with S. aureus presence (0.59, 0.35–0.98). H. influenzae was positively associated with human rhinoviruses (1.63, 1.22–2.18) and respiratory syncytial viruses (2.78, 1.06–7.28). M. catarrhalis colonization was positively associated with coronaviruses (1.99, 1.01–3.93) and adenoviruses (3.69, 1.29–10.56), and negatively with S. aureus carriage (0.42, 0.25–0.69). We observed a strong positive association between S. aureus and influenza viruses (4.87, 1.59–14.89). In addition, human rhinoviruses and enteroviruses were positively correlated (2.40, 1.66–3.47), as were enteroviruses and human bocavirus, WU polyomavirus, parainfluenza viruses, and human parechovirus. A negative association was observed between human rhinoviruses and coronaviruses. CONCLUSIONS/SIGNIFICANCE: Our data revealed high viral and bacterial prevalence rates and distinct bacterial-bacterial, viral-bacterial and viral-viral associations in healthy children, hinting towards the complexity and potential dynamics of microbial communities in the upper respiratory tract. This warrants careful consideration when associating microbial presence with specific respiratory diseases.",2012 Oct 17,"['van den Bergh, Menno R.', 'Biesbroek, Giske', 'Rossen, John W. A.', 'de Steenhuijsen Piters, Wouter A. A.', 'Bosch, Astrid A. T. M.', 'van Gils, Elske J. M.', 'Wang, Xinhui', 'Boonacker, Chantal W. B.', 'Veenhoven, Reinier H.', 'Bruin, Jacob P.', 'Bogaert, Debby', 'Sanders, Elisabeth A. M.']",PLoS One,,,True
d998f77730919d75aa1d19fc3009531447a4d849,PMC,Associations between Pathogens in the Upper Respiratory Tract of Young Children: Interplay between Viruses and Bacteria,http://dx.doi.org/10.1371/journal.pone.0047711,PMC3474735,23082199,CC BY,"BACKGROUND: High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children. Investigating presence of and associations between these pathogens in healthy individuals is still a rather unexplored field of research, but may have implications for interpreting findings during disease. METHODOLOGY/PRINCIPAL FINDINGS: We selected 986 nasopharyngeal samples from 433 6- to 24-month-old healthy children that had participated in a randomized controlled trial. We determined the presence of 20 common respiratory viruses using real-time PCR. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus were identified by conventional culture methods. Information on risk factors was obtained by questionnaires. We performed multivariate logistic regression analyses followed by partial correlation analysis to identify the overall pattern of associations. S. pneumoniae colonization was positively associated with the presence of H. influenzae (adjusted odds ratio 1.60, 95% confidence interval 1.18–2.16), M. catarrhalis (1.78, 1.29–2.47), human rhinoviruses (1.63, 1.19–2.22) and enteroviruses (1.97, 1.26–3.10), and negatively associated with S. aureus presence (0.59, 0.35–0.98). H. influenzae was positively associated with human rhinoviruses (1.63, 1.22–2.18) and respiratory syncytial viruses (2.78, 1.06–7.28). M. catarrhalis colonization was positively associated with coronaviruses (1.99, 1.01–3.93) and adenoviruses (3.69, 1.29–10.56), and negatively with S. aureus carriage (0.42, 0.25–0.69). We observed a strong positive association between S. aureus and influenza viruses (4.87, 1.59–14.89). In addition, human rhinoviruses and enteroviruses were positively correlated (2.40, 1.66–3.47), as were enteroviruses and human bocavirus, WU polyomavirus, parainfluenza viruses, and human parechovirus. A negative association was observed between human rhinoviruses and coronaviruses. CONCLUSIONS/SIGNIFICANCE: Our data revealed high viral and bacterial prevalence rates and distinct bacterial-bacterial, viral-bacterial and viral-viral associations in healthy children, hinting towards the complexity and potential dynamics of microbial communities in the upper respiratory tract. This warrants careful consideration when associating microbial presence with specific respiratory diseases.",2012 Oct 17,"['van den Bergh, Menno R.', 'Biesbroek, Giske', 'Rossen, John W. A.', 'de Steenhuijsen Piters, Wouter A. A.', 'Bosch, Astrid A. T. M.', 'van Gils, Elske J. M.', 'Wang, Xinhui', 'Boonacker, Chantal W. B.', 'Veenhoven, Reinier H.', 'Bruin, Jacob P.', 'Bogaert, Debby', 'Sanders, Elisabeth A. M.']",PLoS One,,,False
9e8a907fcd9c6de7e99c2162e165079936e5d7f4,PMC,Associations between Pathogens in the Upper Respiratory Tract of Young Children: Interplay between Viruses and Bacteria,http://dx.doi.org/10.1371/journal.pone.0047711,PMC3474735,23082199,CC BY,"BACKGROUND: High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children. Investigating presence of and associations between these pathogens in healthy individuals is still a rather unexplored field of research, but may have implications for interpreting findings during disease. METHODOLOGY/PRINCIPAL FINDINGS: We selected 986 nasopharyngeal samples from 433 6- to 24-month-old healthy children that had participated in a randomized controlled trial. We determined the presence of 20 common respiratory viruses using real-time PCR. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus were identified by conventional culture methods. Information on risk factors was obtained by questionnaires. We performed multivariate logistic regression analyses followed by partial correlation analysis to identify the overall pattern of associations. S. pneumoniae colonization was positively associated with the presence of H. influenzae (adjusted odds ratio 1.60, 95% confidence interval 1.18–2.16), M. catarrhalis (1.78, 1.29–2.47), human rhinoviruses (1.63, 1.19–2.22) and enteroviruses (1.97, 1.26–3.10), and negatively associated with S. aureus presence (0.59, 0.35–0.98). H. influenzae was positively associated with human rhinoviruses (1.63, 1.22–2.18) and respiratory syncytial viruses (2.78, 1.06–7.28). M. catarrhalis colonization was positively associated with coronaviruses (1.99, 1.01–3.93) and adenoviruses (3.69, 1.29–10.56), and negatively with S. aureus carriage (0.42, 0.25–0.69). We observed a strong positive association between S. aureus and influenza viruses (4.87, 1.59–14.89). In addition, human rhinoviruses and enteroviruses were positively correlated (2.40, 1.66–3.47), as were enteroviruses and human bocavirus, WU polyomavirus, parainfluenza viruses, and human parechovirus. A negative association was observed between human rhinoviruses and coronaviruses. CONCLUSIONS/SIGNIFICANCE: Our data revealed high viral and bacterial prevalence rates and distinct bacterial-bacterial, viral-bacterial and viral-viral associations in healthy children, hinting towards the complexity and potential dynamics of microbial communities in the upper respiratory tract. This warrants careful consideration when associating microbial presence with specific respiratory diseases.",2012 Oct 17,"['van den Bergh, Menno R.', 'Biesbroek, Giske', 'Rossen, John W. A.', 'de Steenhuijsen Piters, Wouter A. A.', 'Bosch, Astrid A. T. M.', 'van Gils, Elske J. M.', 'Wang, Xinhui', 'Boonacker, Chantal W. B.', 'Veenhoven, Reinier H.', 'Bruin, Jacob P.', 'Bogaert, Debby', 'Sanders, Elisabeth A. M.']",PLoS One,,,False
e2eb9193178fb904a4a5c884b692c82ffc1eca43,PMC,CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2,http://dx.doi.org/10.1371/journal.pone.0047740,PMC3474780,23082204,CC BY,"The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1(−/−) mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1(−/−) peritoneal macrophages demonstrated a 70–75% decrease in the generation of IL-6 and CCL5 (Rantes) in response to the TLR2 agonist Pam(2)CSK(4) and to HSV-1. CD200R1(−/−) macrophages could neither up-regulate the expression of TLR2, nor assemble a functional inflammasome in response to HSV-1. CD200R1(−/−) mice were protected from HSV-1 infection and exhibited dysfunctional TLR2 signaling. Finally, both CD200R1(−/−) mice and CD200R1(−/−) fibroblasts and macrophages showed a markedly reduced ability to support HSV-1 replication. In summary, our data demonstrate an unanticipated and novel requirement for CD200R1 in “licensing” pro-inflammatory functions of TLR2 and in limiting viral replication that are supported by ex vivo and in vivo evidence.",2012 Oct 17,"['Soberman, Roy J.', 'MacKay, Christopher R.', 'Vaine, Christine A.', 'Ryan, Glennice Bowen', 'Cerny, Anna M.', 'Thompson, Mikayla R.', 'Nikolic, Boris', 'Primo, Valeria', 'Christmas, Peter', 'Sheiffele, Paul', 'Aronov, Lisa', 'Knipe, David M.', 'Kurt-Jones, Evelyn A.']",PLoS One,,,True
6040c5668ac30592d68f281e5ecf313060b63d8c,PMC,CD200R1 Supports HSV-1 Viral Replication and Licenses Pro-Inflammatory Signaling Functions of TLR2,http://dx.doi.org/10.1371/journal.pone.0047740,PMC3474780,23082204,CC BY,"The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1(−/−) mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1(−/−) peritoneal macrophages demonstrated a 70–75% decrease in the generation of IL-6 and CCL5 (Rantes) in response to the TLR2 agonist Pam(2)CSK(4) and to HSV-1. CD200R1(−/−) macrophages could neither up-regulate the expression of TLR2, nor assemble a functional inflammasome in response to HSV-1. CD200R1(−/−) mice were protected from HSV-1 infection and exhibited dysfunctional TLR2 signaling. Finally, both CD200R1(−/−) mice and CD200R1(−/−) fibroblasts and macrophages showed a markedly reduced ability to support HSV-1 replication. In summary, our data demonstrate an unanticipated and novel requirement for CD200R1 in “licensing” pro-inflammatory functions of TLR2 and in limiting viral replication that are supported by ex vivo and in vivo evidence.",2012 Oct 17,"['Soberman, Roy J.', 'MacKay, Christopher R.', 'Vaine, Christine A.', 'Ryan, Glennice Bowen', 'Cerny, Anna M.', 'Thompson, Mikayla R.', 'Nikolic, Boris', 'Primo, Valeria', 'Christmas, Peter', 'Sheiffele, Paul', 'Aronov, Lisa', 'Knipe, David M.', 'Kurt-Jones, Evelyn A.']",PLoS One,,,False
5e1989bee9ae95c79dea0e12d9f455cb1d2b61d5,PMC,Critical COPD respiratory illness is linked to increased transcriptomic activity of neutrophil proteases genes,http://dx.doi.org/10.1186/1756-0500-5-401,PMC3475085,22852767,CC BY,"BACKGROUND: Gene expression profiling (GEP) in cells obtained from peripheral blood has shown that this is a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature available on gene expression markers associated with Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated with critical respiratory illness in this disease is not known at the present moment. FINDINGS: By using Agilent microarray chips, we have profiled gene expression signatures in the whole blood of 28 COPD patients hospitalized with different degrees of respiratory compromise.12 of them needed of admission to the ICU, whilst 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparisons of transcript levels between ICU and non-ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to select, annotate and visualize genes by function and pathway (gene ontology). T-test showed evidence of 1501 genes differentially expressed between ICU and non-ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients had increased levels of neutrophil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], and [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This “neutrophil signature” was paralleled by the necessity of advanced respiratory and vital support, and the presence of bacterial infection. CONCLUSION: Study of transcriptomic signatures in blood suggests an essential role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement and modulation of the expression of these genes could present an option for clinical monitoring and treatment of severe COPD exacerbations.",2012 Aug 2,"['Almansa, Raquel', 'Socias, Lorenzo', 'Sanchez-Garcia, Monica', 'Martín-Loeches, Ignacio', 'del Olmo, Milagros', 'Andaluz-Ojeda, David', 'Bobillo, Felipe', 'Rico, Lucia', 'Herrero, Agueda', 'Roig, Vicente', 'San-Jose, C Alicia', 'Rosich, Sara', 'Barbado, Julia', 'Disdier, Carlos', 'de Lejarazu, Raúl Ortiz', 'Gallegos, Maria C', 'Fernandez, Victoria', 'Bermejo-Martin, Jesus F']",BMC Res Notes,,,True
1808454d2e8c7d1088e58a5e3a52111a8c507554,PMC,"Epidemiological, molecular and clinical features of Enterovirus 109 infection in children and in adult stem cell transplant recipients",http://dx.doi.org/10.1186/1743-422X-9-183,PMC3477084,22947270,CC BY,"BACKGROUND: A novel human enterovirus (HEV) type within the species HEV-C, named EV109, was discovered from cases of respiratory illness in Nicaragua in September 2010. The aim of this study, was to retrospectively examine the presence and the role of EV109 in respiratory samples from two patients populations; infants below the age of 2 years, hospitalized for acute respiratory diseases (ARDs) and adult hematopoietic stem cell transplantation recipients. RESULTS: A total of 1149 nasopharingeal aspirates were collected and tested for the presence of EV109 by reverse transcription-PCR (RT-PCR). In positive samples, the presence of the most common respiratory viruses was also assayed and clinical symptoms were evaluated. Samples from 2 of the 974 infants tested positive for EV109 RNA (0.2%) and belonged to patients with lower ARDs; co-infection with other viral pathogens under study was observed in both cases. In transplant recipients, one out of the 175 samples analyzed, from a patients with upper respiratory simptoms tested positive for HEV 109 in the absence of co-infecting viruses. Sequence analysis of amplified EV109 genomic regions, showed only a few nucleotide differences when compared with the Nicaraguan strains. CONCLUSIONS: Overall these results indicate that HEV109 variants have circulated and differentiated in different lineages worldwide. Although more cases and larger studies are needed, HEV109 infection may be associated to ARDs both in infants and in hematopoietic stem cell transplantation recipients. If these preliminary observations will be confirmed, improved molecular methods with a wider panel of potential pathogens will be useful for monitoring these categories of patients.",2012 Sep 4,"['Debiaggi, Maurizia', 'Ceresola, Elisa Rita', 'Sampaolo, Michela', 'Alessandrino, Emilio Paolo', 'Brerra, Roberto', 'Piazza, Aurora', 'Clementi, Massimo', 'Canducci, Filippo']",Virol J,,,True
6177fd107242a0dbf2cfdd0d617e6a384dba6eaa,PMC,Understanding Viral Transmission Behavior via Protein Intrinsic Disorder Prediction: Coronaviruses,http://dx.doi.org/10.1155/2012/738590,PMC3477565,23097708,CC BY,"Besides being a common threat to farm animals and poultry, coronavirus (CoV) was responsible for the human severe acute respiratory syndrome (SARS) epidemic in 2002–4. However, many aspects of CoV behavior, including modes of its transmission, are yet to be fully understood. We show that the amount and the peculiarities of distribution of the protein intrinsic disorder in the viral shell can be used for the efficient analysis of the behavior and transmission modes of CoV. The proposed model allows categorization of the various CoVs by the peculiarities of disorder distribution in their membrane (M) and nucleocapsid (N). This categorization enables quick identification of viruses with similar behaviors in transmission, regardless of genetic proximity. Based on this analysis, an empirical model for predicting the viral transmission behavior is developed. This model is able to explain some behavioral aspects of important coronaviruses that previously were not fully understood. The new predictor can be a useful tool for better epidemiological, clinical, and structural understanding of behavior of both newly emerging viruses and viruses that have been known for a long time. A potentially new vaccine strategy could involve searches for viral strains that are characterized by the evolutionary misfit between the peculiarities of the disorder distribution in their shells and their behavior.",2012 Oct 14,"['Goh, Gerard Kian-Meng', 'Dunker, A. Keith', 'Uversky, Vladimir N.']",J Pathog,,,True
232dc9f3baa927facbe91722ae717e0738a73981,PMC,Genome-wide expression profiling shows transcriptional reprogramming in Fusarium graminearum by Fusarium graminearum virus 1-DK21 infection,http://dx.doi.org/10.1186/1471-2164-13-173,PMC3478160,22559730,CC BY,"BACKGROUND: Fusarium graminearum virus 1 strain-DK21 (FgV1-DK21) is a mycovirus that confers hypovirulence to F. graminearum, which is the primary phytopathogenic fungus that causes Fusarium head blight (FHB) disease in many cereals. Understanding the interaction between mycoviruses and plant pathogenic fungi is necessary for preventing damage caused by F. graminearum. Therefore, we investigated important cellular regulatory processes in a host containing FgV1-DK21 as compared to an uninfected parent using a transcriptional approach. RESULTS: Using a 3′-tiling microarray covering all known F. graminearum genes, we carried out genome-wide expression analyses of F. graminearum at two different time points. At the early point of growth of an infected strain as compared to an uninfected strain, genes associated with protein synthesis, including ribosome assembly, nucleolus, and ribosomal RNA processing, were significantly up-regulated. In addition, genes required for transcription and signal transduction, including fungal-specific transcription factors and cAMP signaling, respectively, were actively up-regulated. In contrast, genes involved in various metabolic pathways, particularly in producing carboxylic acids, aromatic amino acids, nitrogen compounds, and polyamines, showed dramatic down-regulation at the early time point. Moreover, genes associated with transport systems localizing to transmembranes were down-regulated at both time points. CONCLUSION: This is the first report of global change in the prominent cellular pathways in the Fusarium host containing FgV1-DK21. The significant increase in transcripts for transcription and translation machinery in fungal host cells seems to be related to virus replication. In addition, significant down-regulation of genes required for metabolism and transporting systems in a fungal host containing the virus appears to be related to the host defense mechanism and fungal virulence. Taken together, our data aid in the understanding of how FgV1-DK21 regulates the transcriptional reprogramming of F. graminearum.",2012 May 6,"['Cho, Won Kyong', 'Yu, Jisuk', 'Lee, Kyung-Mi', 'Son, Moonil', 'Min, Kyunghun', 'Lee, Yin-Won', 'Kim, Kook-Hyung']",BMC Genomics,,,True
4fce2cc8270c75b0db8e7679d63b40abc5470f6b,PMC,18β-glycyrrhetinic acid inhibits rotavirus replication in culture,http://dx.doi.org/10.1186/1743-422X-9-96,PMC3478227,22616823,CC BY,"BACKGROUND: Glycyrrhizin (GA) and primary metabolite 18β-glycyrrhetinic acid (GRA) are pharmacologically active components of the medicinal licorice root, and both have been shown to have antiviral and immunomodulatory properties. Although these properties are well established, the mechanisms of action are not completely understood. In this study, GA and GRA were tested for the ability to inhibit rotavirus replication in cell culture, toward a long term goal of discovering natural compounds that may complement existing vaccines. METHODS: Epithelial cells were treated with GA or GRA various times pre- or post-infection and virus yields were measured by immunofluorescent focus assay. Levels of viral proteins VP2, VP6, and NSP2 in GRA treated cells were measured by immunoblot to determine if there was an effect of GRA treatment on the accumulation of viral protein. RESULTS: GRA treatment reduced rotavirus yields by 99% when added to infected cultures post-- virus adsorption, whereas virus yields in GA treated cultures were similar to mock treated controls. Time of addition experiments indicated that GRA-mediated replication inhibition likely occurs at a step or steps subsequent to virus entry. The amounts of VP2, VP6 and NSP2 were substantially reduced when GRA was added to cultures up to two hours post-entry. CONCLUSIONS: GRA, but not GA, has significant antiviral activity against rotavirus replication in vitro, and studies to determine whether GRA attenuates rotavirus replication in vivo are underway.",2012 May 22,"['Hardy, Michele E', 'Hendricks, Jay M', 'Paulson, Jeana M', 'Faunce, Nicholas R']",Virol J,,,True
8a6f367d81903273daadb6e142149f2feff80d6e,PMC,"Interplay of foot-and-mouth disease virus, antibodies and plasmacytoid dendritic cells: virus opsonization under non-neutralizing conditions results in enhanced interferon-alpha responses",http://dx.doi.org/10.1186/1297-9716-43-64,PMC3479418,22934974,CC BY,"Foot-and-mouth disease virus (FMDV) is a highly infectious member of the Picornaviridae inducing an acute disease of cloven-hoofed species. Vaccine-induced immune protection correlates with the presence of high levels of neutralizing antibodies but also opsonising antibodies have been proposed as an important mechanism of the immune response contributing to virus clearance by macrophages and leading to the production of type-I interferon (IFN) by plasmacytoid dendritic cells (pDC). The present study demonstrates that the opsonising antibody titres mediating enhanced IFN-α responses in pDC were similar to neutralizing titres, when antigenically related viruses from the same serotype were employed. However, sera cross-reacted also with non-neutralized isolates of multiple serotypes, when tested in this assay. Both uncomplexed virus and immune complexed virus stimulated pDC via Toll-like receptor 7. An additional finding of potential importance for strain-specific differences in virulence and/or immunogenicity was that pDC activation by FMDV strongly differed between viral isolates. Altogether, our results indicate that opsonising antibodies can have a broader reactivity than neutralizing antibodies and may contribute to antiviral responses induced against antigenically distant viruses.",2012 Aug 30,"['Lannes, Nils', 'Python, Sylvie', 'Summerfield, Artur']",Vet Res,,,True
8b13309e21cd13564b46ef8d78bf927cf558f6f1,PMC,A Three-Dimensional Comparison of Tick-Borne Flavivirus Infection in Mammalian and Tick Cell Lines,http://dx.doi.org/10.1371/journal.pone.0047912,PMC3480448,23112871,CC0,"Tick-borne flaviviruses (TBFV) are sustained in nature through cycling between mammalian and tick hosts. In this study, we used African green monkey kidney cells (Vero) and Ixodes scapularis tick cells (ISE6) to compare virus-induced changes in mammalian and arthropod cells. Using confocal microscopy, transmission electron microscopy (TEM), and electron tomography (ET), we examined viral protein distribution and the ultrastructural changes that occur during TBFV infection. Within host cells, flaviviruses cause complex rearrangement of cellular membranes for the purpose of virus replication. Virus infection was accompanied by a marked expansion in endoplasmic reticulum (ER) staining and markers for TBFV replication were localized mainly to the ER in both cell lines. TEM of Vero cells showed membrane-bound vesicles enclosed in a network of dilated, anastomosing ER cisternae. Virions were seen within the ER and were sometimes in paracrystalline arrays. Tubular structures or elongated vesicles were occasionally noted. In acutely and persistently infected ISE6 cells, membrane proliferation and vesicles were also noted; however, the extent of membrane expansion and the abundance of vesicles were lower and no viral particles were observed. Tubular profiles were far more prevalent in persistently infected ISE6 cells than in acutely infected cells. By ET, tubular profiles, in persistently infected tick cells, had a cross-sectional diameter of 60–100 nm, reached up to 800 nm in length, were closed at the ends, and were often arranged in fascicle-like bundles, shrouded with ER membrane. Our experiments provide analysis of viral protein localization within the context of both mammalian and arthropod cell lines as well as both acute and persistent arthropod cell infection. Additionally, we show for the first time 3D flavivirus infection in a vector cell line and the first ET of persistent flavivirus infection.",2012 Oct 24,"['Offerdahl, Danielle K.', 'Dorward, David W.', 'Hansen, Bryan T.', 'Bloom, Marshall E.']",PLoS One,,,True
ce05a808109c6307485aeda93945cd3b0e536623,PMC,"SEED Servers: High-Performance Access to the SEED Genomes, Annotations, and Metabolic Models",http://dx.doi.org/10.1371/journal.pone.0048053,PMC3480482,23110173,CC0,"The remarkable advance in sequencing technology and the rising interest in medical and environmental microbiology, biotechnology, and synthetic biology resulted in a deluge of published microbial genomes. Yet, genome annotation, comparison, and modeling remain a major bottleneck to the translation of sequence information into biological knowledge, hence computational analysis tools are continuously being developed for rapid genome annotation and interpretation. Among the earliest, most comprehensive resources for prokaryotic genome analysis, the SEED project, initiated in 2003 as an integration of genomic data and analysis tools, now contains >5,000 complete genomes, a constantly updated set of curated annotations embodied in a large and growing collection of encoded subsystems, a derived set of protein families, and hundreds of genome-scale metabolic models. Until recently, however, maintaining current copies of the SEED code and data at remote locations has been a pressing issue. To allow high-performance remote access to the SEED database, we developed the SEED Servers (http://www.theseed.org/servers): four network-based servers intended to expose the data in the underlying relational database, support basic annotation services, offer programmatic access to the capabilities of the RAST annotation server, and provide access to a growing collection of metabolic models that support flux balance analysis. The SEED servers offer open access to regularly updated data, the ability to annotate prokaryotic genomes, the ability to create metabolic reconstructions and detailed models of metabolism, and access to hundreds of existing metabolic models. This work offers and supports a framework upon which other groups can build independent research efforts. Large integrations of genomic data represent one of the major intellectual resources driving research in biology, and programmatic access to the SEED data will provide significant utility to a broad collection of potential users.",2012 Oct 24,"['Aziz, Ramy K.', 'Devoid, Scott', 'Disz, Terrence', 'Edwards, Robert A.', 'Henry, Christopher S.', 'Olsen, Gary J.', 'Olson, Robert', 'Overbeek, Ross', 'Parrello, Bruce', 'Pusch, Gordon D.', 'Stevens, Rick L.', 'Vonstein, Veronika', 'Xia, Fangfang']",PLoS One,,,True
15029a39f0a27d1bbccb6fed1793ea25700d9e57,PMC,"SEED Servers: High-Performance Access to the SEED Genomes, Annotations, and Metabolic Models",http://dx.doi.org/10.1371/journal.pone.0048053,PMC3480482,23110173,CC0,"The remarkable advance in sequencing technology and the rising interest in medical and environmental microbiology, biotechnology, and synthetic biology resulted in a deluge of published microbial genomes. Yet, genome annotation, comparison, and modeling remain a major bottleneck to the translation of sequence information into biological knowledge, hence computational analysis tools are continuously being developed for rapid genome annotation and interpretation. Among the earliest, most comprehensive resources for prokaryotic genome analysis, the SEED project, initiated in 2003 as an integration of genomic data and analysis tools, now contains >5,000 complete genomes, a constantly updated set of curated annotations embodied in a large and growing collection of encoded subsystems, a derived set of protein families, and hundreds of genome-scale metabolic models. Until recently, however, maintaining current copies of the SEED code and data at remote locations has been a pressing issue. To allow high-performance remote access to the SEED database, we developed the SEED Servers (http://www.theseed.org/servers): four network-based servers intended to expose the data in the underlying relational database, support basic annotation services, offer programmatic access to the capabilities of the RAST annotation server, and provide access to a growing collection of metabolic models that support flux balance analysis. The SEED servers offer open access to regularly updated data, the ability to annotate prokaryotic genomes, the ability to create metabolic reconstructions and detailed models of metabolism, and access to hundreds of existing metabolic models. This work offers and supports a framework upon which other groups can build independent research efforts. Large integrations of genomic data represent one of the major intellectual resources driving research in biology, and programmatic access to the SEED data will provide significant utility to a broad collection of potential users.",2012 Oct 24,"['Aziz, Ramy K.', 'Devoid, Scott', 'Disz, Terrence', 'Edwards, Robert A.', 'Henry, Christopher S.', 'Olsen, Gary J.', 'Olson, Robert', 'Overbeek, Ross', 'Parrello, Bruce', 'Pusch, Gordon D.', 'Stevens, Rick L.', 'Vonstein, Veronika', 'Xia, Fangfang']",PLoS One,,,True
630a27f09c2caab65471e97cf1d538d364a2498a,PMC,"First report of Toxoplasma gondii seroprevalence in peafowls in Yunnan Province, Southwestern China",http://dx.doi.org/10.1186/1756-3305-5-205,PMC3480843,22992281,CC BY,"BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite infecting almost all warm-blooded animals, including birds, with a worldwide distribution. Surveys of T. gondii infection in wild birds have been reported extensively in the world, but little is known of T. gondii infection in peafowls worldwide. This study was performed to determine the seroprevalence of T. gondii infection in peafowls in Yunnan Province, southwestern China. METHODS: Sera from 277 peafowls, including 272 blue peafowls (Pavo cristatus) and 5 green peafowls (Pavo muticus) originated from two geographic areas in Yunnan Province were assayed for T. gondii antibodies using the modified agglutination test (MAT). RESULTS: Specific T. gondii antibodies were detected in 35 of 277 (12.64%) peafowls (MAT titer ≥ 1:5). Seropositive birds were found in both species, 33 in 272 blue peafowls and 2 in 5 green peafowls. There was no significant difference in T. gondii seroprevalence between the adolescent birds (6.74%) and the adult birds (6.67%) (P > 0.05). The geographical origins of peafowls was found to be highly associated with T. gondii infection in the present study, a statistically significant difference in T. gondii seropositivity was observed between peafowls from Kunming (31.08%) and those from Xishuangbanna Dai Autonomous Prefecture (5.91%) (OR = 10.956, 95% CI = 1.632-73.545, P = 0.014). Statistical analyses showed that there were no significant interactions between ages and geographical origins of peafowls (P > 0.05). CONCLUSIONS: The results of the present survey indicated that infection of peafowls with T. gondii is widespread in Yunnan Province, which has significant public health concerns and implications for prevention and control of toxoplamosis in this province. To our knowledge, this is the first seroprevalence report of T. gondii infection in China’s southwestern Yunnan Province.",2012 Sep 19,"['Tian, Yi-Ming', 'Dai, Fei-Yan', 'Huang, Si-Yang', 'Deng, Zu-Hong', 'Duan, Gang', 'Zhou, Dong-Hui', 'Yang, Jian-Fa', 'Weng, Ya-Biao', 'Zhu, Xing-Quan', 'Zou, Feng-Cai']",Parasit Vectors,,,True
69d2e69e949dab8909be8c7b764a0d5469546b31,PMC,Evaluation of reference genes for real-time quantitative PCR studies in Candida glabrata following azole treatment,http://dx.doi.org/10.1186/1471-2199-13-22,PMC3482582,22747760,CC BY,"BACKGROUND: The selection of stable and suitable reference genes for real-time quantitative PCR (RT-qPCR) is a crucial prerequisite for reliable gene expression analysis under different experimental conditions. The present study aimed to identify reference genes as internal controls for gene expression studies by RT-qPCR in azole-stimulated Candida glabrata. RESULTS: The expression stability of 16 reference genes under fluconazole stress was evaluated using fold change and standard deviation computations with the hkgFinder tool. Our data revealed that the mRNA expression levels of three ribosomal RNAs (RDN5.8, RDN18, and RDN25) remained stable in response to fluconazole, while PGK1, UBC7, and UBC13 mRNAs showed only approximately 2.9-, 3.0-, and 2.5-fold induction by azole, respectively. By contrast, mRNA levels of the other 10 reference genes (ACT1, EF1α, GAPDH, PPIA, RPL2A, RPL10, RPL13A, SDHA, TUB1, and UBC4) were dramatically increased in C. glabrata following antifungal treatment, exhibiting changes ranging from 4.5- to 32.7-fold. We also assessed the expression stability of these reference genes using the 2(-ΔΔCT) method and three other software packages. The stability rankings of the reference genes by geNorm and the 2(-ΔΔCT) method were identical to those by hkgFinder, whereas the stability rankings by BestKeeper and NormFinder were notably different. We then validated the suitability of six candidate reference genes (ACT1, PGK1, RDN5.8, RDN18, UBC7, and UBC13) as internal controls for ten target genes in this system using the comparative C(T) method. Our validation experiments passed for all six reference genes analyzed except RDN18, where the amplification efficiency of RDN18 was different from that of the ten target genes. Finally, we demonstrated that the relative quantification of target gene expression varied according to the endogenous control used, highlighting the importance of the choice of internal controls in such experiments. CONCLUSIONS: We recommend the use of RDN5.8, UBC13, and PGK1 alone or the combination of RDN5.8 plus UBC13 or PGK1 as reference genes for RT-qPCR analysis of gene expression in C. glabrata following azole treatment. In contrast, we show that ACT1 and other commonly used reference genes (GAPDH, PPIA, RPL13A, TUB1, etc.) were not validated as good internal controls in the current model.",2012 Jun 29,"['Li, Qingdi Quentin', 'Skinner, Jeff', 'Bennett, John E']",BMC Mol Biol,,,True
02a9fd5f564cb3a5b6b1fdbcd9df585b8e24a2de,PMC,Performance Evaluation of the Maxwell 16 System for Extraction of Influenza Virus RNA from Diverse Samples,http://dx.doi.org/10.1371/journal.pone.0048094,PMC3483271,23144730,CC BY,"This study evaluated the performance of the Maxwell 16 System (Promega) for extraction of influenza virus (flu-v) RNA from diverse samples compared to a classical manual method (QIAamp Kit, QIAGEN). Following extraction by the two methods, all samples were analyzed by Real-time RT-PCR. Results revealed that the use of the standard Maxwell 16 protocol (Maxwell 16-S) resulted in good linearity and precision across a wide concentration range and higher sensitivity of detection from flu-v stock suspensions than the manual method. Compared with the latter method, Maxwell 16-S extracted RNA more efficiently (higher RNA yield and/or fewer PCR inhibitors) from throat swabs and bronchoalveolar lavage fluids, while both methods performed comparably on fecal samples from human and poultry in terms of overall threshold cycle values and detection rates although the Maxwell 16-S co-purified more inhibitors from fecal samples. The capacity of this system to remove inhibitors from fecal matrix was improved by using a modified Maxwell 16 protocol with a reduced sample input, which eliminated all false-negatives produced by the Maxwell 16-S. These findings suggest that the Maxwell 16 System is suitable for RNA extraction from multiple-source samples for diagnosis of influenza and viral load determination and that a proper reduction in starting sample volume may improve the detection of flu-v from complex matrices such as feces. Additionally, this system allows flexible sample throughput and labor-saving sample processing with little or no risk of cross-contamination.",2012 Oct 29,"['Liu, Hongbo', 'Gan, Yan', 'Yang, Bo', 'Weng, Hui', 'Huang, Chunmei', 'Yang, Daofeng', 'Lei, Ping', 'Shen, Guanxin']",PLoS One,,,True
c9fca01d18bac485ae1c5257a712c516aeea8408,PMC,Discovery and Targeted LC-MS/MS of Purified Polerovirus Reveals Differences in the Virus-Host Interactome Associated with Altered Aphid Transmission,http://dx.doi.org/10.1371/journal.pone.0048177,PMC3484124,23118947,CC0,"Circulative transmission of viruses in the Luteoviridae, such as cereal yellow dwarf virus (CYDV), requires a series of precisely orchestrated interactions between virus, plant, and aphid proteins. Natural selection has favored these viruses to be retained in the phloem to facilitate acquisition and transmission by aphids. We show that treatment of infected oat tissue homogenate with sodium sulfite reduces transmission of the purified virus by aphids. Transmission electron microscopy data indicated no gross change in virion morphology due to treatments. However, treated virions were not acquired by aphids through the hindgut epithelial cells and were not transmitted when injected directly into the hemocoel. Analysis of virus preparations using nanoflow liquid chromatography coupled to tandem mass spectrometry revealed a number of host plant proteins co-purifying with viruses, some of which were lost following sodium sulfite treatment. Using targeted mass spectrometry, we show data suggesting that several of the virus-associated host plant proteins accumulated to higher levels in aphids that were fed on CYDV-infected plants compared to healthy plants. We propose two hypotheses to explain these observations, and these are not mutually exclusive: (a) that sodium sulfite treatment disrupts critical virion-host protein interactions required for aphid transmission, or (b) that host infection with CYDV modulates phloem protein expression in a way that is favorable for virus uptake by aphids. Importantly, the genes coding for the plant proteins associated with virus may be examined as targets in breeding cereal crops for new modes of virus resistance that disrupt phloem-virus or aphid-virus interactions.",2012 Oct 30,"['Cilia, Michelle', 'Peter, Kari A.', 'Bereman, Michael S.', 'Howe, Kevin', 'Fish, Tara', 'Smith, Dawn', 'Gildow, Fredrick', 'MacCoss, Michael J.', 'Thannhauser, Theodore W.', 'Gray, Stewart M.']",PLoS One,,,True
8a71eeb8c75ab05167e5d0a6ac12e6f8d6eb61fd,PMC,Discovery and Targeted LC-MS/MS of Purified Polerovirus Reveals Differences in the Virus-Host Interactome Associated with Altered Aphid Transmission,http://dx.doi.org/10.1371/journal.pone.0048177,PMC3484124,23118947,CC0,"Circulative transmission of viruses in the Luteoviridae, such as cereal yellow dwarf virus (CYDV), requires a series of precisely orchestrated interactions between virus, plant, and aphid proteins. Natural selection has favored these viruses to be retained in the phloem to facilitate acquisition and transmission by aphids. We show that treatment of infected oat tissue homogenate with sodium sulfite reduces transmission of the purified virus by aphids. Transmission electron microscopy data indicated no gross change in virion morphology due to treatments. However, treated virions were not acquired by aphids through the hindgut epithelial cells and were not transmitted when injected directly into the hemocoel. Analysis of virus preparations using nanoflow liquid chromatography coupled to tandem mass spectrometry revealed a number of host plant proteins co-purifying with viruses, some of which were lost following sodium sulfite treatment. Using targeted mass spectrometry, we show data suggesting that several of the virus-associated host plant proteins accumulated to higher levels in aphids that were fed on CYDV-infected plants compared to healthy plants. We propose two hypotheses to explain these observations, and these are not mutually exclusive: (a) that sodium sulfite treatment disrupts critical virion-host protein interactions required for aphid transmission, or (b) that host infection with CYDV modulates phloem protein expression in a way that is favorable for virus uptake by aphids. Importantly, the genes coding for the plant proteins associated with virus may be examined as targets in breeding cereal crops for new modes of virus resistance that disrupt phloem-virus or aphid-virus interactions.",2012 Oct 30,"['Cilia, Michelle', 'Peter, Kari A.', 'Bereman, Michael S.', 'Howe, Kevin', 'Fish, Tara', 'Smith, Dawn', 'Gildow, Fredrick', 'MacCoss, Michael J.', 'Thannhauser, Theodore W.', 'Gray, Stewart M.']",PLoS One,,,False
99bef7780df3f4c309e62e9aa33ec62753052623,PMC,Discovery and Targeted LC-MS/MS of Purified Polerovirus Reveals Differences in the Virus-Host Interactome Associated with Altered Aphid Transmission,http://dx.doi.org/10.1371/journal.pone.0048177,PMC3484124,23118947,CC0,"Circulative transmission of viruses in the Luteoviridae, such as cereal yellow dwarf virus (CYDV), requires a series of precisely orchestrated interactions between virus, plant, and aphid proteins. Natural selection has favored these viruses to be retained in the phloem to facilitate acquisition and transmission by aphids. We show that treatment of infected oat tissue homogenate with sodium sulfite reduces transmission of the purified virus by aphids. Transmission electron microscopy data indicated no gross change in virion morphology due to treatments. However, treated virions were not acquired by aphids through the hindgut epithelial cells and were not transmitted when injected directly into the hemocoel. Analysis of virus preparations using nanoflow liquid chromatography coupled to tandem mass spectrometry revealed a number of host plant proteins co-purifying with viruses, some of which were lost following sodium sulfite treatment. Using targeted mass spectrometry, we show data suggesting that several of the virus-associated host plant proteins accumulated to higher levels in aphids that were fed on CYDV-infected plants compared to healthy plants. We propose two hypotheses to explain these observations, and these are not mutually exclusive: (a) that sodium sulfite treatment disrupts critical virion-host protein interactions required for aphid transmission, or (b) that host infection with CYDV modulates phloem protein expression in a way that is favorable for virus uptake by aphids. Importantly, the genes coding for the plant proteins associated with virus may be examined as targets in breeding cereal crops for new modes of virus resistance that disrupt phloem-virus or aphid-virus interactions.",2012 Oct 30,"['Cilia, Michelle', 'Peter, Kari A.', 'Bereman, Michael S.', 'Howe, Kevin', 'Fish, Tara', 'Smith, Dawn', 'Gildow, Fredrick', 'MacCoss, Michael J.', 'Thannhauser, Theodore W.', 'Gray, Stewart M.']",PLoS One,,,False
02fe68e2ba45e7f0c6f746d4b3db36f8f99ae4f5,PMC,Communicable disease control in China: From Mao to now,,PMC3484775,23198121,CC BY,"China’s progress on communicable disease control (CDC) in the 30 years after establishment of the People’s Republic in 1949 is widely regarded as remarkable. Life expectancy soared by around 30 years, infant mortality plummeted and smallpox, sexually transmitted diseases and many other infections were either eliminated or decreased massively in incidence, largely as a result of CDC. By the mid-1970s, China was already undergoing the epidemiologic transition, years ahead of other nations of similar economic status. These early successes can be attributed to population mobilization, mass campaigns and a focus on sanitation, hygiene, clean water and clean delivery, and occurred despite political instability and slow economic progress. The 10-year Cultural Revolution from 1966 brought many hardships, but also clinical care and continuing public health programs to the masses through community-funded medical schemes and the establishment of community-based health workers. These people-focused approaches broke down with China’s market reforms from 1980. Village doctors turned to private practice as community funding ceased, and the attention paid to rural public health declined. CDC relied on vertical programs, some of them successful (such as elimination of lymphatic filariasis and child immunisation), but others (such as control of schistosomiasis and tuberculosis) demonstrating only intermittent progress due to failed strategies or reliance on support by the poorest governments and health workers, who could not or would not collaborate. In addition, China’s laissez-faire approach to public health placed it at great risk, as evidenced by the outbreak in 2003 of the Severe Acute Respiratory Syndrome. Since then, major changes to disease reporting, the priority given to CDC including through major new domestic resources and reform of China’s health system offer encouragement for CDC. While decentralized funding and varying quality diagnosis, reporting and treatment of infectious diseases remain major challenges, national priority on CDC in China is high.",2011 Dec,"Hipgrave, David",J Glob Health,,,True
1d4793842e3eeae37f34abb1541b0cee61ff976d,PMC,"Mortality, Severe Acute Respiratory Infection, and Influenza-Like Illness Associated with Influenza A(H1N1)pdm09 in Argentina, 2009",http://dx.doi.org/10.1371/journal.pone.0047540,PMC3485247,23118877,CC0,"INTRODUCTION: While there is much information about the burden of influenza A(H1N1)pdm09 in North America, little data exist on its burden in South America. METHODS: During April to December 2009, we actively searched for persons with severe acute respiratory infection and influenza-like illness (ILI) in three sentinel cities. A proportion of case-patients provided swabs for influenza testing. We estimated the number of case-patients that would have tested positive for influenza by multiplying the number of untested case-patients by the proportion who tested positive. We estimated rates by dividing the estimated number of case-patients by the census population after adjusting for the proportion of case-patients with missing illness onset information and ILI case-patients who visited physicians multiple times for one illness event. RESULTS: We estimated that the influenza A(H1N1)pdm09 mortality rate per 100,000 person-years (py) ranged from 1.5 among persons aged 5–44 years to 5.6 among persons aged ≥65 years. A(H1N1)pdm09 hospitalization rates per 100,000 py ranged between 26.9 among children aged <5 years to 41.8 among persons aged ≥65 years. Influenza A(H1N1)pdm09 ILI rates per 100 py ranged between 1.6 among children aged <5 to 17.1 among persons aged 45–64 years. While 9 (53%) of 17 influenza A(H1N1)pdm09 decedents with available data had obesity and 7 (17%) of 40 had diabetes, less than 4% of surviving influenza A(H1N1)pdm09 case-patients had these pre-existing conditions (p≤0.001). CONCLUSION: Influenza A(H1N1)pdm09 caused a similar burden of disease in Argentina as in other countries. Such disease burden suggests the potential value of timely influenza vaccinations.",2012 Oct 31,"['Azziz-Baumgartner, Eduardo', 'Cabrera, Ana María', 'Chang, Loretta', 'Calli, Rogelio', 'Kusznierz, Gabriela', 'Baez, Clarisa', 'Yedlin, Pablo', 'Zamora, Ana María', 'Cuezzo, Romina', 'Sarrouf, Elena Beatriz', 'Uboldi, Andrea', 'Herrmann, Juan', 'Zerbini, Elsa', 'Uez, Osvaldo', 'Rico Cordeiro, Pedro Osvaldo', 'Chavez, Pollyanna', 'Han, George', 'Antman, Julián', 'Coronado, Fatima', 'Bresee, Joseph', 'Kosacoff, Marina', 'Widdowson, Marc-Alain', 'Echenique, Horacio']",PLoS One,,,True
f0fb3bbd96dad4c907c7fd456cd5783ed8fa7bd6,PMC,"C. difficile 630Δerm Spo0A Regulates Sporulation, but Does Not Contribute to Toxin Production, by Direct High-Affinity Binding to Target DNA",http://dx.doi.org/10.1371/journal.pone.0048608,PMC3485338,23119071,CC BY,"Clostridium difficile is a Gram positive, anaerobic bacterium that can form highly resistant endospores. The bacterium is the causative agent of C. difficile infection (CDI), for which the symptoms can range from a mild diarrhea to potentially fatal pseudomembranous colitis and toxic megacolon. Endospore formation in Firmicutes, including C. difficile, is governed by the key regulator for sporulation, Spo0A. In Bacillus subtilis, this transcription factor is also directly or indirectly involved in various other cellular processes. Here, we report that C. difficile Spo0A shows a high degree of similarity to the well characterized B. subtilis protein and recognizes a similar binding sequence. We find that the laboratory strain C. difficile 630Δerm contains an 18bp-duplication near the DNA-binding domain compared to its ancestral strain 630. In vitro binding assays using purified C-terminal DNA binding domain of the C. difficile Spo0A protein demonstrate direct binding to DNA upstream of spo0A and sigH, early sporulation genes and several other putative targets. In vitro binding assays suggest that the gene encoding the major clostridial toxin TcdB may be a direct target of Spo0A, but supernatant derived from a spo0A negative strain was no less toxic towards Vero cells than that obtained from a wild type strain, in contrast to previous reports. These results identify for the first time direct (putative) targets of the Spo0A protein in C. difficile and make a positive effect of Spo0A on production of the large clostridial toxins unlikely.",2012 Oct 31,"['Rosenbusch, Katharina E.', 'Bakker, Dennis', 'Kuijper, Ed J.', 'Smits, Wiep Klaas']",PLoS One,,,True
6ee4fb1e1119adb4af83b4f22b2b9142cb3c9c75,PMC,"C. difficile 630Δerm Spo0A Regulates Sporulation, but Does Not Contribute to Toxin Production, by Direct High-Affinity Binding to Target DNA",http://dx.doi.org/10.1371/journal.pone.0048608,PMC3485338,23119071,CC BY,"Clostridium difficile is a Gram positive, anaerobic bacterium that can form highly resistant endospores. The bacterium is the causative agent of C. difficile infection (CDI), for which the symptoms can range from a mild diarrhea to potentially fatal pseudomembranous colitis and toxic megacolon. Endospore formation in Firmicutes, including C. difficile, is governed by the key regulator for sporulation, Spo0A. In Bacillus subtilis, this transcription factor is also directly or indirectly involved in various other cellular processes. Here, we report that C. difficile Spo0A shows a high degree of similarity to the well characterized B. subtilis protein and recognizes a similar binding sequence. We find that the laboratory strain C. difficile 630Δerm contains an 18bp-duplication near the DNA-binding domain compared to its ancestral strain 630. In vitro binding assays using purified C-terminal DNA binding domain of the C. difficile Spo0A protein demonstrate direct binding to DNA upstream of spo0A and sigH, early sporulation genes and several other putative targets. In vitro binding assays suggest that the gene encoding the major clostridial toxin TcdB may be a direct target of Spo0A, but supernatant derived from a spo0A negative strain was no less toxic towards Vero cells than that obtained from a wild type strain, in contrast to previous reports. These results identify for the first time direct (putative) targets of the Spo0A protein in C. difficile and make a positive effect of Spo0A on production of the large clostridial toxins unlikely.",2012 Oct 31,"['Rosenbusch, Katharina E.', 'Bakker, Dennis', 'Kuijper, Ed J.', 'Smits, Wiep Klaas']",PLoS One,,,False
fcc1c06c4e3e68af5aba453e42a50bdf45f99ff0,PMC,"C. difficile 630Δerm Spo0A Regulates Sporulation, but Does Not Contribute to Toxin Production, by Direct High-Affinity Binding to Target DNA",http://dx.doi.org/10.1371/journal.pone.0048608,PMC3485338,23119071,CC BY,"Clostridium difficile is a Gram positive, anaerobic bacterium that can form highly resistant endospores. The bacterium is the causative agent of C. difficile infection (CDI), for which the symptoms can range from a mild diarrhea to potentially fatal pseudomembranous colitis and toxic megacolon. Endospore formation in Firmicutes, including C. difficile, is governed by the key regulator for sporulation, Spo0A. In Bacillus subtilis, this transcription factor is also directly or indirectly involved in various other cellular processes. Here, we report that C. difficile Spo0A shows a high degree of similarity to the well characterized B. subtilis protein and recognizes a similar binding sequence. We find that the laboratory strain C. difficile 630Δerm contains an 18bp-duplication near the DNA-binding domain compared to its ancestral strain 630. In vitro binding assays using purified C-terminal DNA binding domain of the C. difficile Spo0A protein demonstrate direct binding to DNA upstream of spo0A and sigH, early sporulation genes and several other putative targets. In vitro binding assays suggest that the gene encoding the major clostridial toxin TcdB may be a direct target of Spo0A, but supernatant derived from a spo0A negative strain was no less toxic towards Vero cells than that obtained from a wild type strain, in contrast to previous reports. These results identify for the first time direct (putative) targets of the Spo0A protein in C. difficile and make a positive effect of Spo0A on production of the large clostridial toxins unlikely.",2012 Oct 31,"['Rosenbusch, Katharina E.', 'Bakker, Dennis', 'Kuijper, Ed J.', 'Smits, Wiep Klaas']",PLoS One,,,False
23d8bce7be2d5afed730addd3b4531f1bc721da6,PMC,Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus,http://dx.doi.org/10.7554/eLife.00049,PMC3485615,23150796,CC BY,"Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV. DOI: http://dx.doi.org/10.7554/eLife.00049.001",2012 Nov 13,"['Yan, Huan', 'Zhong, Guocai', 'Xu, Guangwei', 'He, Wenhui', 'Jing, Zhiyi', 'Gao, Zhenchao', 'Huang, Yi', 'Qi, Yonghe', 'Peng, Bo', 'Wang, Haimin', 'Fu, Liran', 'Song, Mei', 'Chen, Pan', 'Gao, Wenqing', 'Ren, Bijie', 'Sun, Yinyan', 'Cai, Tao', 'Feng, Xiaofeng', 'Sui, Jianhua', 'Li, Wenhui']",eLife,,,True
dc5765fa88deec41d804ff9f32a2211b30a021d1,PMC,Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus,http://dx.doi.org/10.7554/eLife.00049,PMC3485615,23150796,CC BY,"Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV. DOI: http://dx.doi.org/10.7554/eLife.00049.001",2012 Nov 13,"['Yan, Huan', 'Zhong, Guocai', 'Xu, Guangwei', 'He, Wenhui', 'Jing, Zhiyi', 'Gao, Zhenchao', 'Huang, Yi', 'Qi, Yonghe', 'Peng, Bo', 'Wang, Haimin', 'Fu, Liran', 'Song, Mei', 'Chen, Pan', 'Gao, Wenqing', 'Ren, Bijie', 'Sun, Yinyan', 'Cai, Tao', 'Feng, Xiaofeng', 'Sui, Jianhua', 'Li, Wenhui']",eLife,,,False
b79088a023db89b12d5630e426661985aba3921e,PMC,The Evolutionary Pattern of Glycosylation Sites in Influenza Virus (H5N1) Hemagglutinin and Neuraminidase,http://dx.doi.org/10.1371/journal.pone.0049224,PMC3486865,23133677,CC BY,"Two glycoproteins, hemagglutinin (HA) and neuraminidase (NA), on the surface of influenza viruses play crucial roles in transfaunation, membrane fusion and the release of progeny virions. To explore the distribution of N-glycosylation sites (glycosites) in these two glycoproteins, we collected and aligned the amino acid sequences of all the HA and NA subtypes. Two glycosites were located at HA0 cleavage sites and fusion peptides and were strikingly conserved in all HA subtypes, while the remaining glycosites were unique to their subtypes. Two to four conserved glycosites were found in the stalk domain of NA, but these are affected by the deletion of specific stalk domain sequences. Another highly conserved glycosite appeared at the top center of tetrameric global domain, while the others glycosites were distributed around the global domain. Here we present a detailed investigation of the distribution and the evolutionary pattern of the glycosites in the envelope glycoproteins of IVs, and further focus on the H5N1 virus and conclude that the glycosites in H5N1 have become more complicated in HA and less influential in NA in the last five years.",2012 Nov 1,"['Chen, Wentian', 'Zhong, Yaogang', 'Qin, Yannan', 'Sun, Shisheng', 'Li, Zheng']",PLoS One,,,True
513cb067ae66876bca5e55d343cf196b8d5715e9,PMC,Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral Effects,http://dx.doi.org/10.1371/journal.ppat.1002976,PMC3486884,23133371,CC BY,"Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+)-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.",2012 Oct 25,"['Jurgeit, Andreas', 'McDowell, Robert', 'Moese, Stefan', 'Meldrum, Eric', 'Schwendener, Reto', 'Greber, Urs F.']",PLoS Pathog,,,True
a50f3a7514dd9363e42a1eff725a7eb3e49b6ed2,PMC,Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral Effects,http://dx.doi.org/10.1371/journal.ppat.1002976,PMC3486884,23133371,CC BY,"Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+)-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.",2012 Oct 25,"['Jurgeit, Andreas', 'McDowell, Robert', 'Moese, Stefan', 'Meldrum, Eric', 'Schwendener, Reto', 'Greber, Urs F.']",PLoS Pathog,,,True
319896275e7fe7dacb19138689294224c13a1aeb,PMC,A Single Residue Substitution in the Receptor-Binding Domain of H5N1 Hemagglutinin Is Critical for Packaging into Pseudotyped Lentiviral Particles,http://dx.doi.org/10.1371/journal.pone.0043596,PMC3487904,23133587,CC BY,"BACKGROUND: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed. METHODOLOGY/FINDINGS: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134. CONCLUSIONS: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 viruses.",2012 Nov 2,"['Tang, Dong-Jiang', 'Lam, Yuen-Man', 'Siu, Yu-Lam', 'Lam, Chi-Hong', 'Chu, Shui-Ling', 'Peiris, J. S. Malik', 'Buchy, Philippe', 'Nal, Béatrice', 'Bruzzone, Roberto']",PLoS One,,,True
7c19aadb1294d6b98fc8b947a98eefac0da6b870,PMC,Visual detection of the human metapneumovirus using reverse transcription loop-mediated isothermal amplification with hydroxynaphthol blue dye,http://dx.doi.org/10.1186/1743-422X-9-138,PMC3487928,22838725,CC BY,"BACKGROUND: Human metapneumovirus (hMPV) is a major cause of acute respiratory infections ranging from wheezing to bronchiolitis and pneumonia in children worldwide. The objective of this study is to develop a visual reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of hMPV and applied to the clinical samples. RESULTS: In this study, visual RT-LAMP assay for hMPV was performed in one step with the addition of hydroxynaphthol blue (HNB), and were used to detect respiratory samples. Six primers, including two outer primers (F3 and B3), two inner primers (FIP, BIP) and two loop primers (LF and LB), were designed for hMPV N gene by the online software. Moreover, the RT-LAMP assay showed good specificity and no cross-reactivity was observed with human rhinovirus (HRV), human respiratory syncytial Virus (RSV), or influenza virus A/PR/8/34 (H1N1). The detection limit of the RT-LAMP assay was approximately ten viral RNA copies, lower than that of traditional reverse transcriptase polymerase chain reaction (RT-PCR) 100 RNA copies. In the 176 nasopharyngeal samples, 23 (13.1%) were conformed as hMPV positive by RT-LAMP, but 18 (10.2%) positive by RT-PCR. CONCLUSION: Compared with conventional RT-PCR, the visual hMPV RT-LAMP assay performed well in the aspect of detect time, sensitivity, specificity and visibility. It is anticipated that the RT-LAMP will be used for clinical tests in hospital or field testing during outbreaks and in emergency.",2012 Jul 27,"['Wang, Xiang', 'Zhang, Qian', 'Zhang, Fang', 'Ma, Fenlian', 'Zheng, Wenzhi', 'Zhao, Zhihui', 'Bai, Yinglong', 'Zheng, Lishu']",Virol J,,,True
c0f05769898b94c3e481a16c7fee9666037bbdab,PMC,Isolation and characterization of a variant porcine epidemic diarrhea virus in China,http://dx.doi.org/10.1186/1743-422X-9-195,PMC3487931,22967434,CC BY,"An outbreak of diarrhea in pigs started in Guangdong, South China in January 2011. Cases were characterized by watery diarrhea, dehydration and vomiting, with 80–100% morbidity and 50–90% mortality in suckling piglets. The causative agent of the diarrhea was ultimately identified as porcine epidemic diarrhea virus (PEDV). In this study, we isolated a PEDV strain designated CHGD-01 from piglet intestines using Vero cell cultures, and its specific cytopathic effects were confirmed in susceptible cells by direct immunofluorescence testing and electron microscopy. The complete genome of CHGD-01 was shown to be 28,035 nucleotides in length, with a similar structure to that of PEDV reference strains. Phylogenetic analyses based on the whole genome revealed that CHGD-01 shared nucleotide sequence identities of 98.2–98.4% with two other Chinese isolates reported in the same year, thus constituting a new cluster. Amino acid sequence analysis based on individual virus genes indicated a close relationship between the spike protein gene of CHGD-01 and the field strain KNU0802 in Korea. Its ORF3 and nucleoprotein genes, however, were divergent from all other sequenced PEDV isolate clusters and therefore formed a new group, suggesting a new variant PEDV isolate in China. Further studies will be required to determine the immunogenicity and pathogenicity of this new variant.",2012 Sep 12,"['Pan, Yongfei', 'Tian, Xiaoyan', 'Li, Wei', 'Zhou, Qingfeng', 'Wang, Dongdong', 'Bi, Yingzuo', 'Chen, Feng', 'Song, Yanhua']",Virol J,,,True
e9c8c9036e9dd48230c81ff006be5fceba73660f,PMC,"Megapneumonia Coinfection: pneumococcus, Mycoplasma pneumoniae, and Metapneumovirus",http://dx.doi.org/10.1155/2012/310104,PMC3488377,23193411,CC BY,"We report a young girl who died of Streptococcus pneumoniae 19A pneumonia, septic shock, and hemolytic uremic syndrome despite prior pneumococcal vaccination, appropriate antibiotics, and aggressive intensive care support. Serotype 19A is not covered by the 7- or 10-valent pneumococcal vaccines. Mycoplasma pneumoniae and metapneumovirus were simultaneously detected by PCR in the nasopharyngeal and tracheal aspirates. The pneumococcus is penicillin sensitive. Although infections with each of these pathogens alone are typically mild, this case highlights that co-infection with the triple respiratory pathogens possibly contributed to the fatal outcome of this child. Also, the new policy in Hong Kong to use PCV13 may help prevent further cases of serotype 19A infections.",2012 Oct 17,"['Hon, Kam Lun', 'Ip, Margaret', 'Chu, Winnie Chiu Wing', 'Wong, William']",Case Rep Med,,,True
45a03a7fbd289f6da276b1c0bab12e09337b9ffd,PMC,H1N1 Influenza Viral Infection in a Postpartum Young Woman Causes Respiratory Failure: What the Care Providers Ought to Know?,http://dx.doi.org/10.1155/2012/419528,PMC3488388,23150842,CC BY,"Pregnant and postpartum women are considered a population at increased risk of hospitalization of H1N1 infection. We report the case of a young postpartum woman, who developed evidence of respiratory failure reaching the point of requiring intubation due to an H1N1 influenza virus infection two days after a caesarean delivery. We emphasize the diagnosis, management, and the outcome focusing on the question “what the care providers, including obstetric health care workers, ought to know?” Diagnostic and management strategy for pregnant or postpartum women with novel influenza A (H1N1) viral infection and increased awareness amongst patients and health care professionals may result in improved survival.",2012 Oct 23,"['Aloizos, Stavros', 'Aravosita, Paraskevi', 'Mystakelli, Christina', 'Kanna, Efthymia', 'Gourgiotis, Stavros']",Case Rep Pulmonol,,,True
b2ca7959b768af6c0ac1f5e347a31dacf9fcfd2f,PMC,Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike protein induces systemic and mucosal immunity without redirection of the virus to the brain,http://dx.doi.org/10.1186/1743-422X-9-215,PMC3489719,22995185,CC BY,"BACKGROUND: Sublingual (s.l.) administration of soluble protein antigens, inactivated viruses, or virus-like particles has been shown to induce broad immune responses in mucosal and extra-mucosal tissues. Recombinant replication-defective adenovirus vectors (rADVs) infect mucosa surface and therefore can serve as a mucosal antigen delivery vehicle. In this study we examined whether s.l. immunization with rADV encoding spike protein (S) (rADV-S) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) induces protective immunity against SARS-CoV and could serve as a safe mucosal route for delivery of rADV. RESULTS: Here, we show that s.l. administration of rADV-S induced serum SARS-CoV neutralizing and airway IgA antibodies in mice. These antibody responses are comparable to those induced by intranasal (i.n.) administration. In addition, s.l. immunization induced antigen-specific CD8(+) T cell responses in the lungs that are superior to those induced by intramuscular immunization. Importantly, unlike i.n. administration, s.l. immunization with rADV did not redirect the rADV vector to the olfactory bulb. CONCLUSION: Our study indicates that s.l. immunization with rADV-S is safe and effective in induction of a broad spectrum of immune responses and presumably protection against infection with SARS-CoV.",2012 Sep 21,"['Shim, Byoung-Shik', 'Stadler, Konrad', 'Nguyen, Huan Huu', 'Yun, Cheol-Heui', 'Kim, Dong Wook', 'Chang, Jun', 'Czerkinsky, Cecil', 'Song, Man Ki']",Virol J,,,True
e1a771476018079cd6dcb063ae78e04ca349ba08,PMC,Airway protease/antiprotease imbalance in atopic asthmatics contributes to increased Influenza A virus cleavage and replication,http://dx.doi.org/10.1186/1465-9921-13-82,PMC3489803,22992220,CC BY,"Asthmatics are more susceptible to influenza infections, yet mechanisms mediating this enhanced susceptibility are unknown. Influenza virus hemagglutinin (HA) protein binds to sialic acid residues on the host cells. HA requires cleavage to allow fusion of the viral HA with host cell membrane, which is mediated by host trypsin-like serine protease. We show data here demonstrating that the protease:antiprotease ratio is increased in the nasal mucosa of asthmatics and that these changes were associated with increased proteolytic activation of influenza. These data suggest that disruption of the protease balance in asthmatics enhances activation and infection of influenza virus.",2012 Sep 19,"['Kesic, Matthew J', 'Hernandez, Michelle', 'Jaspers, Ilona']",Respir Res,,,True
2aad3ed695f9313c14066aa2c385092c7cf814b2,PMC,The expression of nicotinic receptor alpha7 during cochlear development,http://dx.doi.org/10.1002/brb3.84,PMC3489815,23139908,CC BY,"Nicotinic acetylcholine receptor alpha7 expression was examined in the developing and adult auditory system using mice that were modified through homologous recombination to coexpress either GFP (alpha7GFP) or Cre (alpha7Cre), respectively. The expression of alpha7GFP is first detected at embryonic (E) day E13.5 in cells of the spiral prominence. By E14.5, sensory regions including the putative outer hair cells and Deiters' cells express alpha7GFP as do solitary efferent fibers. This pattern diminishes after E16.5 in a basal to apex progression, as Hensen's cells and cells of the spiral ligament acquire alpha7GFP expression. At birth and thereafter alpha7GFP also identifies a subset of spiral ganglion cells whose processes terminate on inner hair cells. Efferent fibers identified by peripherin or calcitonin gene-related protein do not coexpress alpha7GFP. In addition to cochlear structures, there is strong expression of alpha7GFP by cells of the central auditory pathways including the ventral posterior cochlear nucleus, lateral lemniscus, central inferior colliculus, and the medial geniculate nucleus. Our findings suggest that alpha7 expression by both neuronal and non-neuronal cells has the potential to impact multiple auditory functions through mechanisms that are not traditionally attributed to this receptor.",2012 Sep 23,"['Rogers, Scott W', 'Myers, Elizabeth J', 'Gahring, Lorise C']",Brain Behav,,,True
cab83150f6a2199249918297638108ce1c45e4e4,PMC,The alcohol industry lobby and Hong Kong’s zero wine and beer tax policy,http://dx.doi.org/10.1186/1471-2458-12-717,PMC3490743,22935365,CC BY,"BACKGROUND: Whereas taxation on alcohol is becoming an increasingly common practice in many countries as part of overall public health measures, the Hong Kong Special Administrative Region Government is bucking the trend and lowered its duties on wine and beer by 50 percent in 2007. In 2008, Hong Kong removed all duties on alcohol except for spirits. The aim of this paper is to examine the case of Hong Kong with its history of changes in alcohol taxation to explore the factors that have driven such an unprecedented policy evolution. METHODS: The research is based on an analysis of primary documents. Searches of official government documents, alcohol-related industry materials and other media reports on alcohol taxation for the period from 2000 to 2008 were systematically carried out using key terms such as “alcohol tax” and “alcohol industry”. Relevant documents (97) were indexed by date and topic to undertake a chronological and thematic analysis using Nvivo8 software. RESULTS: Our analysis demonstrates that whereas the city’s changing financial circumstances and the Hong Kong Special Administrative Region Government’s strong propensity towards economic liberalism had, in part, contributed to such dramatic transformation, the alcohol industry’s lobbying tactics and influence were clearly the main drivers of the policy decision. The alcohol industry’s lobbying tactics were two-fold. The first was to forge a coalition encompassing a range of catering and trade industries related to alcohol as well as industry-friendly lawmakers so that these like-minded actors could find common ground in pursuing changes to the taxation policy. The second was to deliberately promote a blend of ideas to garner support from the general public and to influence the perception of key policy makers. CONCLUSIONS: Our findings suggest that the success of aggressive industry lobbying coupled with the absence of robust public health advocacy was the main driving force behind the unparalleled abolition of wine and beer duties in Hong Kong. Strong public health alliance and advocacy movement are needed to counteract the industry’s continuing aggressive lobby and promotion of alcoholic beverages.",2012 Aug 30,"['Yoon, Sungwon', 'Lam, Tai-Hing']",BMC Public Health,,,True
54ebc03fe88092d143f0758472adf54252d6c224,PMC,Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis C virus in cell culture,http://dx.doi.org/10.1186/1743-422X-9-143,PMC3490746,22863531,CC BY,"BACKGROUND: Hepatic steatosis is recognized as a major risk factor for liver disease progression and impaired response to interferon based therapy in chronic hepatitis C (CHC) patients. The mechanism of response to interferon-alpha (IFN-α) therapy under the condition of hepatic steatosis is unexplored. We investigated the effect of hepatocellular steatosis on hepatitis C virus (HCV) replication and IFN-α antiviral response in a cell culture model. METHODS: Sub-genomic replicon (S3-GFP) and HCV infected Huh-7.5 cells were cultured with a mixture of saturated (palmitate) and unsaturated (oleate) long-chain free fatty acids (FFA). Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry. The effect of FFA treatment on HCV replication and IFN-α antiviral response was measured by flow cytometric analysis, Renilla luciferase activity, and real-time RT-PCR. RESULTS: FFA treatment induced dose dependent hepatocellular steatosis and lipid droplet accumulation in the HCV replicon cells was confirmed by Nile red staining, microfluorometry, and by electron microscopy. Intracellular fat accumulation supports replication more in the persistently HCV infected culture than in the sub-genomic replicon (S3-GFP) cell line. FFA treatment also partially blocked IFN-α response and viral clearance by reducing the phosphorylation of Stat1 and Stat2 dependent IFN-β promoter activation. We show that FFA treatment induces endoplasmic reticulum (ER) stress response and down regulates the IFNAR1 chain of the type I IFN receptor leading to defective Jak-Stat signaling and impaired antiviral response. CONCLUSION: These results suggest that intracellular fat accumulation in HCV cell culture induces ER stress, defective Jak-Stat signaling, and attenuates the antiviral response, thus providing an explanation to the clinical observation regarding how hepatocellular steatosis influences IFN-α response in CHC.",2012 Aug 3,"['Gunduz, Feyza', 'Aboulnasr, Fatma M', 'Chandra, Partha K', 'Hazari, Sidhartha', 'Poat, Bret', 'Baker, Darren P', 'Balart, Luis A', 'Dash, Srikanta']",Virol J,,,True
da9c223fd6f69816aca093a7d2ab333fe9b21ee1,PMC,Identification of serum proteomic biomarkers for early porcine reproductive and respiratory syndrome (PRRS) infection,http://dx.doi.org/10.1186/1477-5956-10-48,PMC3492009,22873815,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine diseases worldwide. Despite its relevance, serum biomarkers associated with early-onset viral infection, when clinical signs are not detectable and the disease is characterized by a weak anti-viral response and persistent infection, have not yet been identified. Surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) is a reproducible, accurate, and simple method for the identification of biomarker proteins related to disease in serum. This work describes the SELDI-TOF MS analyses of sera of 60 PRRSV-positive and 60 PRRSV-negative, as measured by PCR, asymptomatic Large White piglets at weaning. Sera with comparable and low content of hemoglobin (< 4.52 μg/mL) were fractionated in 6 different fractions by anion-exchange chromatography and protein profiles in the mass range 1–200 kDa were obtained with the CM10, IMAC30, and H50 surfaces. RESULTS: A total of 200 significant peaks (p < 0.05) were identified in the initial discovery phase of the study and 47 of them were confirmed in the validation phase. The majority of peaks (42) were up-regulated in PRRSV-positive piglets, while 5 were down-regulated. A panel of 14 discriminatory peaks identified in fraction 1 (pH = 9), on the surface CM10, and acquired at low focus mass provided a serum protein profile diagnostic pattern that enabled to discriminate between PRRSV-positive and -negative piglets with a sensitivity and specificity of 77% and 73%, respectively. CONCLUSIONS: SELDI-TOF MS profiling of sera from PRRSV-positive and PRRSV-negative asymptomatic piglets provided a proteomic signature with large scale diagnostic potential for early identification of PRRSV infection in weaning piglets. Furthermore, SELDI-TOF protein markers represent a refined phenotype of PRRSV infection that might be useful for whole genome association studies.",2012 Aug 8,"['Genini, Sem', 'Paternoster, Thomas', 'Costa, Alessia', 'Botti, Sara', 'Luini, Mario Vittorio', 'Caprera, Andrea', 'Giuffra, Elisabetta']",Proteome Sci,,,True
f9c39fa24056184c67ec47da4da93ba583c36e84,PMC,In vitro inhibition of transmissible gastroenteritis coronavirus replication in swine testicular cells by short hairpin RNAs targeting the ORF 7 gene,http://dx.doi.org/10.1186/1743-422X-9-176,PMC3492083,22929207,CC BY,"BACKGROUND: Transmissible gastroenteritis (TGE) is a highly contagious viral disease of swine, characterized by severe vomiting, diarrhea, and high mortality. Currently, the vaccines for it are only partially effective and no specific drug is available for treatment of TGE virus (TGEV) infection. RNA interference has been confirmed as a new approach for controlling viral infections. In this study, the inhibitory effect of short hairpin RNAs (shRNAs) targeting the ORF 7 gene of TGEV on virus replication was examined. RESULTS: Four theoretically effective sequences of TGEV ORF 7 gene were designed and selected for construction of shRNA expression plasmids. In the reporter assays, three of four shRNA expression plasmids were able to inhibit significantly the expression of ORF 7 gene and replication of TGEV, as shown by real-time quantitative RT-PCR analysis of viral ORF 7 and N genes and detection of virus titers (TCID(50)/ml). Stable swine testicular (ST) cells expressing the shRNAs were established. Observation of the cytopathic effect and apoptosis, as well as a cell proliferation assay demonstrated that the three shRNAs were capable of protecting ST cells against TGEV destruction, with high specificity and efficiency. CONCLUSIONS: Our results indicated that plasmid-transcribed shRNAs targeting the ORF 7 gene in the TGEV genome effectively inhibited expression of the viral target gene and viral replication in vitro. These findings provide evidence that the shRNAs have potential therapeutic application for treatment of TGE.",2012 Aug 28,"['He, Lei', 'Zhang, Yan-ming', 'Dong, Ling-juan', 'Cheng, Min', 'Wang, Jing', 'Tang, Qing-hai', 'Wang, Gang']",Virol J,,,True
8ce3ae4141f74a6ef60175581277687d6c185b4d,PMC,Social determinants of health in Canada: Are healthy living initiatives there yet? A policy analysis,http://dx.doi.org/10.1186/1475-9276-11-41,PMC3492195,22889402,CC BY,"INTRODUCTION: Preventative strategies that focus on addressing the social determinants of health to improve healthy eating and physical activity have become an important strategy in British Columbia and Ontario for combating chronic diseases. What has not yet been examined is the extent to which healthy living initiatives implemented under these new policy frameworks successfully engage with and change the social determinants of health. METHODS: Initiatives active between January 1, 2006 and September 1, 2011 were found using provincial policy documents, web searches, health organization and government websites, and databases of initiatives that attempted to influence to nutrition and physical activity in order to prevent chronic diseases or improve overall health. Initiatives were reviewed, analyzed and grouped using the descriptive codes: lifestyle-based, environment-based or structure-based. Initiatives were also classified according to the mechanism by which they were administered: as direct programs (e.g. directly delivered), blueprints (or frameworks to tailor developed programs), and building blocks (resources to develop programs). RESULTS: 60 initiatives were identified in Ontario and 61 were identified in British Columbia. In British Columbia, 11.5% of initiatives were structure-based. In Ontario, of 60 provincial initiatives identified, 15% were structure-based. Ontario had a higher proportion of direct interventions than British Columbia for all intervention types. However, in both provinces, as the intervention became more upstream and attempted to target the social determinants of health more directly, the level of direct support for the intervention lessened. CONCLUSIONS: The paucity of initiatives in British Columbia and Ontario that address healthy eating and active living through action on the social determinants of health is problematic. In the context of Canada's increasingly neoliberal political and economic policy, the public health sector may face significant barriers to addressing upstream determinants in a meaningful way. If public health cannot directly affect broader societal conditions, interventions should be focused around advocacy and education about the social determinants of health. It is necessary that health be seen for what it is: a political matter. As such, the health sector needs to take a more political approach in finding solutions for health inequities.",2012 Aug 14,"['Gore, Dana', 'Kothari, Anita']",Int J Equity Health,,,True
01c6ab71344d688b1b44fd2095d891d126152499,PMC,Social determinants of health in Canada: Are healthy living initiatives there yet? A policy analysis,http://dx.doi.org/10.1186/1475-9276-11-41,PMC3492195,22889402,CC BY,"INTRODUCTION: Preventative strategies that focus on addressing the social determinants of health to improve healthy eating and physical activity have become an important strategy in British Columbia and Ontario for combating chronic diseases. What has not yet been examined is the extent to which healthy living initiatives implemented under these new policy frameworks successfully engage with and change the social determinants of health. METHODS: Initiatives active between January 1, 2006 and September 1, 2011 were found using provincial policy documents, web searches, health organization and government websites, and databases of initiatives that attempted to influence to nutrition and physical activity in order to prevent chronic diseases or improve overall health. Initiatives were reviewed, analyzed and grouped using the descriptive codes: lifestyle-based, environment-based or structure-based. Initiatives were also classified according to the mechanism by which they were administered: as direct programs (e.g. directly delivered), blueprints (or frameworks to tailor developed programs), and building blocks (resources to develop programs). RESULTS: 60 initiatives were identified in Ontario and 61 were identified in British Columbia. In British Columbia, 11.5% of initiatives were structure-based. In Ontario, of 60 provincial initiatives identified, 15% were structure-based. Ontario had a higher proportion of direct interventions than British Columbia for all intervention types. However, in both provinces, as the intervention became more upstream and attempted to target the social determinants of health more directly, the level of direct support for the intervention lessened. CONCLUSIONS: The paucity of initiatives in British Columbia and Ontario that address healthy eating and active living through action on the social determinants of health is problematic. In the context of Canada's increasingly neoliberal political and economic policy, the public health sector may face significant barriers to addressing upstream determinants in a meaningful way. If public health cannot directly affect broader societal conditions, interventions should be focused around advocacy and education about the social determinants of health. It is necessary that health be seen for what it is: a political matter. As such, the health sector needs to take a more political approach in finding solutions for health inequities.",2012 Aug 14,"['Gore, Dana', 'Kothari, Anita']",Int J Equity Health,,,False
9663932b573dbf156ca3ca89873b43a62ea3a6fa,PMC,Social determinants of health in Canada: Are healthy living initiatives there yet? A policy analysis,http://dx.doi.org/10.1186/1475-9276-11-41,PMC3492195,22889402,CC BY,"INTRODUCTION: Preventative strategies that focus on addressing the social determinants of health to improve healthy eating and physical activity have become an important strategy in British Columbia and Ontario for combating chronic diseases. What has not yet been examined is the extent to which healthy living initiatives implemented under these new policy frameworks successfully engage with and change the social determinants of health. METHODS: Initiatives active between January 1, 2006 and September 1, 2011 were found using provincial policy documents, web searches, health organization and government websites, and databases of initiatives that attempted to influence to nutrition and physical activity in order to prevent chronic diseases or improve overall health. Initiatives were reviewed, analyzed and grouped using the descriptive codes: lifestyle-based, environment-based or structure-based. Initiatives were also classified according to the mechanism by which they were administered: as direct programs (e.g. directly delivered), blueprints (or frameworks to tailor developed programs), and building blocks (resources to develop programs). RESULTS: 60 initiatives were identified in Ontario and 61 were identified in British Columbia. In British Columbia, 11.5% of initiatives were structure-based. In Ontario, of 60 provincial initiatives identified, 15% were structure-based. Ontario had a higher proportion of direct interventions than British Columbia for all intervention types. However, in both provinces, as the intervention became more upstream and attempted to target the social determinants of health more directly, the level of direct support for the intervention lessened. CONCLUSIONS: The paucity of initiatives in British Columbia and Ontario that address healthy eating and active living through action on the social determinants of health is problematic. In the context of Canada's increasingly neoliberal political and economic policy, the public health sector may face significant barriers to addressing upstream determinants in a meaningful way. If public health cannot directly affect broader societal conditions, interventions should be focused around advocacy and education about the social determinants of health. It is necessary that health be seen for what it is: a political matter. As such, the health sector needs to take a more political approach in finding solutions for health inequities.",2012 Aug 14,"['Gore, Dana', 'Kothari, Anita']",Int J Equity Health,,,False
b1b9699bbe9b36657ae6aa66628dc06e232da95b,PMC,"Serological evidence of ebolavirus infection in bats, China",http://dx.doi.org/10.1186/1743-422X-9-236,PMC3492202,23062147,CC BY,"BACKGROUND: The genus Ebolavirus of the family Filoviridae currently consists of five species. All species, with the exception of Reston ebolavirus, have been found in Africa and caused severe human diseases. Bats have been implicated as reservoirs for ebolavirus. Reston ebolavirus, discovered in the Philippines, is the only ebolavirus species identified in Asia to date. Whether this virus is prevalent in China is unknown. FINDINGS: In this study, we developed an enzyme linked immunosorbent assay (ELISA) for ebolavirus using the recombinant nucleocapsid protein and performed sero-surveillance for the virus among Chinese bat populations. Our results revealed the presence of antibodies to ebolavirus in 32 of 843 bat sera samples and 10 of 16 were further confirmed by western blot analysis. CONCLUSION: To our knowledge, this is the first report of any filovirus infection in China.",2012 Oct 13,"['Yuan, Junfa', 'Zhang, Yuji', 'Li, Jialu', 'Zhang, Yunzhi', 'Wang, Lin-Fa', 'Shi, Zhengli']",Virol J,,,True
883b77a8f0dfe0d099e0ceb77531f18fc8a6b2a9,PMC,Immunogenetic Variation and Differential Pathogen Exposure in Free-Ranging Cheetahs across Namibian Farmlands,http://dx.doi.org/10.1371/journal.pone.0049129,PMC3492310,23145096,CC BY,"BACKGROUND: Genes under selection provide ecologically important information useful for conservation issues. Major histocompatibility complex (MHC) class I and II genes are essential for the immune defence against pathogens from intracellular (e.g. viruses) and extracellular (e.g. helminths) origins, respectively. Serosurvey studies in Namibian cheetahs (Acinonyx juabuts) revealed higher exposure to viral pathogens in individuals from north-central than east-central regions. Here we examined whether the observed differences in exposure to viruses influence the patterns of genetic variation and differentiation at MHC loci in 88 free-ranging Namibian cheetahs. METHODOLOGY/PRINCIPAL FINDINGS: Genetic variation at MHC I and II loci was assessed through single-stranded conformation polymorphism (SSCP) analysis and sequencing. While the overall allelic diversity did not differ, we observed a high genetic differentiation at MHC class I loci between cheetahs from north-central and east-central Namibia. No such differentiation in MHC class II and neutral markers were found. CONCLUSIONS/SIGNIFICANCE: Our results suggest that MHC class I variation mirrors the variation in selection pressure imposed by viruses in free-ranging cheetahs across Namibian farmland. This is of high significance for future management and conservation programs of this species.",2012 Nov 7,"['Castro-Prieto, Aines', 'Wachter, Bettina', 'Melzheimer, Joerg', 'Thalwitzer, Susanne', 'Hofer, Heribert', 'Sommer, Simone']",PLoS One,,,True
5678f2e8dc1710c96b5f4e5ae8d6ddae9c5e6580,PMC,Production and characterization of human anti-V3 monoclonal antibodies from the cells of HIV-1 infected Indian donors,http://dx.doi.org/10.1186/1743-422X-9-196,PMC3493341,22971578,CC BY,"BACKGROUND: Analysis of human monoclonal antibodies (mAbs) developed from HIV-1 infected donors have enormously contributed to the identification of neutralization sensitive epitopes on the HIV-1 envelope glycoprotein. The third variable region (V3) is a crucial target on gp120, primarily due to its involvement in co-receptor (CXCR4 or CCR5) binding and presence of epitopes recognized by broadly neutralizing antibodies. METHODS: Thirty-three HIV-1 seropositive drug naive patients (18 males and 15 females) within the age range of 20–57 years (median = 33 years) were recruited in this study for mAb production. The mAbs were selected from EBV transformed cultures with conformationally constrained Cholera-toxin-B containing V3C (V3C-CTB) fusion protein. We tested the mAbs for their binding with HIV-1 derived proteins and peptides by ELISA and for neutralization against HIV-1 viruses by TZM-bl assays. RESULTS: We isolated three anti-V3 mAbs, 277, 903 and 904 from the cells of different individuals. The ELISA binding revealed a subtype-C and subtype-A specific binding of antibody 277 and 903 while mAb 904 exhibited cross reactivity also with subtype-B V3. Epitope mapping of mAbs with overlapping V3 peptides showed exclusive binding to V3 crown. The antibodies displayed high and low neutralizing activity against 2/5 tier 1 and 1/6 tier 2 viruses respectively. Overall, we observed a resistance of the tier 2 viruses to neutralization by the anti-V3 mAbs, despite the exposure of the epitopes recognized by these antibodies on two representative native viruses (Du156.12 and JRFL), suggesting that the affinity of mAb might equally be crucial for neutralization, as the epitope recognition. CONCLUSIONS: Our study suggests that the anti-V3 antibodies derived from subtype-C infected Indian patients display neutralization potential against tier 1 viruses while such activity may be limited against more resistant tier 2 viruses. Defining the fine epitope specificities of these mAbs and further experimental manipulations will be helpful in identification of epitopes, unique to clade C or shared with non-clade C viruses, in context of V3 region.",2012 Sep 12,"['Andrabi, Raiees', 'Kumar, Rajesh', 'Bala, Manju', 'Nair, Ambili', 'Biswas, Ashutosh', 'Wig, Naveet', 'Kumar, Pratik', 'Pal, Rahul', 'Sinha, Subrata', 'Luthra, Kalpana']",Virol J,,,True
624d182cc7495a9fd996eb51663e8774a42d2cca,PMC,Evidence-based support for the all-hazards approach to emergency preparedness,http://dx.doi.org/10.1186/2045-4015-1-40,PMC3494498,23098065,CC BY,"BACKGROUND: During the last decade there has been a need to respond and recover from various types of emergencies including mass casualty events (MCEs), mass toxicological/chemical events (MTEs), and biological events (pandemics and bio-terror agents). Effective emergency preparedness is more likely to be achieved if an all-hazards response plan is adopted. OBJECTIVES: To investigate if there is a relationship among hospitals' preparedness for various emergency scenarios, and whether components of one emergency scenario correlate with preparedness for other emergency scenarios. METHODS: Emergency preparedness levels of all acute-care hospitals for MCEs, MTEs, and biological events were evaluated, utilizing a structured evaluation tool based on measurable parameters. Evaluations were made by professional experts in two phases: evaluation of standard operating procedures (SOPs) followed by a site visit. Relationships among total preparedness and different components' scores for various types of emergencies were analyzed. RESULTS: Significant relationships were found among preparedness for different emergencies. Standard Operating Procedures (SOPs) for biological events correlated with preparedness for all investigated emergency scenarios. Strong correlations were found between training and drills with preparedness for all investigated emergency scenarios. CONCLUSIONS: Fundamental critical building blocks such as SOPs, training, and drill programs improve preparedness for different emergencies including MCEs, MTEs, and biological events, more than other building blocks, such as equipment or knowledge of personnel. SOPs are especially important in unfamiliar emergency scenarios. The findings support the adoption of an all-hazards approach to emergency preparedness.",2012 Oct 25,"['Adini, Bruria', 'Goldberg, Avishay', 'Cohen, Robert', 'Laor, Daniel', 'Bar-Dayan, Yaron']",Isr J Health Policy Res,,,True
2b10c237281a6e5d61e8fff995dc8920465eda56,PMC,"Simultaneous Detection and Differentiation of Human Papillomavirus Genotypes 6, 11, 16 and 18 by AllGlo Quadruplex Quantitative PCR",http://dx.doi.org/10.1371/journal.pone.0048972,PMC3494670,23152833,CC BY,"BACKGROUND: Human papillomaviruses (HPV) are classified into high-risk HPV and low-risk HPV. The most common high-risk HPV types in cervical cancer are HPV 16 and 18, and the most common low-risk types causing genital warts are HPV 6 and HPV 11. In this study, applying novel AllGlo fluorescent probes, we established a quadruplex quantitative PCR method to simultaneously detect and differentiate HPV 6, 11, 16 and 18 in a single tube. METHODS: The specificity, the sensitivity, the detection limit, the reproducibility and the standard curve of this method were examined. Finally, clinical samples that had been tested previously by TaqMan PCR and HPV GenoArray (GA) test were used to verify the accuracy and sensitivity of the method. RESULTS: The assay has a sensitivity of 10(1) to 10(2) copies/test and a linear detection range from 10(1) to 10(8) copies/test. The mean amplification efficiencies for HPV 6, 11, 16, and 18 were 0.97, 1.10, 0.93 and 1.20, respectively, and the mean correlation coefficient (r(2)) of each standard curve was above 0.99 for plasmid templates ranging from 10(3) to 10(7) copies/test. There was 100% agreement between the AllGlo quadruplex quantitative PCR, HPV GA test and TaqMan uniplex qPCR methods. CONCLUSIONS: AllGlo quadruplex quantitative PCR in a single tube has the advantages of relatively high throughput, good reproducibility, high sensitivity, high specificity, and a wide linear range of detection. The convenient single tube format makes this assay a powerful tool for the studies of mixed infections by multiple pathogens, viral typing and viral load quantification.",2012 Nov 9,"['Yu, Daojun', 'Chen, Yu', 'Wu, Shenghai', 'Wang, Baohong', 'Tang, Yi-Wei', 'Li, Lanjuan']",PLoS One,,,True
bf7d69e6d9d85c3870025ee9e51632ca44283441,PMC,Epitope mapping by random peptide phage display reveals essential residues for vaccinia extracellular enveloped virion spread,http://dx.doi.org/10.1186/1743-422X-9-217,PMC3495767,23006741,CC BY,"BACKGROUND: A33 is a type II integral membrane protein expressed on the extracellular enveloped form of vaccinia virus (VACV). Passive transfer of A33-directed monoclonal antibodies or vaccination with an A33 subunit vaccine confers protection against lethal poxvirus challenge in animal models. Homologs of A33 are highly conserved among members of the Orthopoxvirus genus and are potential candidates for inclusion in vaccines or assays targeting extracellular enveloped virus activity. One monoclonal antibody directed against VACV A33, MAb-1G10, has been shown to target a conformation-dependent epitope. Interestingly, while it recognizes VACV A33 as well as the corresponding variola homolog, it does not bind to the monkeypox homolog. In this study, we utilized a random phage display library to investigate the epitope recognized by MAb-1G10 that is critical for facilitating cell-to-cell spread of the vaccinia virus. RESULTS: By screening with linear or conformational random phage libraries, we found that phages binding to MAb-1G10 display the consensus motif CEPLC, with a disulfide bond formed between two cysteine residues required for MAb-1G10 binding. Although the phage motif contained no linear sequences homologous to VACV A33, structure modeling and analysis suggested that residue D115 is important to form the minimal epitope core. A panel of point mutants expressing the ectodomain of A33 protein was generated and analyzed by either binding assays such as ELISA and immunoprecipitation or a functional assessment by blocking MAb-1G10 mediated comet inhibition in cell culture. CONCLUSIONS: These results confirm L118 as a component of the MAb-1G10 binding epitope, and further identify D115 as an essential residue. By defining the minimum conformational structure, as well as the conformational arrangement of a short peptide sequence recognized by MAb-1G10, these results introduce the possibility of designing small molecule mimetics that may interfere with the function of A33 in vivo. This information will also be useful for designing improved assays to evaluate the potency of monoclonal and polyclonal products that target A33 or A33-modulated EV dissemination.",2012 Sep 24,"['He, Yong', 'Wang, Yonggang', 'Struble, Evi B', 'Zhang, Pei', 'Chowdhury, Soma', 'Reed, Jennifer L', 'Kennedy, Michael', 'Scott, Dorothy E', 'Fisher, Robert W']",Virol J,,,True
f2b40d30efe21fe521d22798d4c0e185e4ad6799,PMC,PCR based bronchoscopic detection of common respiratory pathogens in chronic cough: a case control study,http://dx.doi.org/10.1186/1745-9974-8-5,PMC3496690,22978556,CC BY,"BACKGROUND: Viral respiratory tract infection is the most frequent cause of acute cough and is reported at onset in about one third of patients with chronic cough. Persistent infection is therefore one possible explanation for the cough reflex hypersensitivity and pulmonary inflammation reported in chronic cough patients. METHODS: Bronchoscopic endobronchial biopsies and bronchoalveolar lavage cell counts were obtained from ten healthy volunteers and twenty treatment resistant chronic cough patients (10 selected for lavage lymphocytosis). A screen for known respiratory pathogens was performed on biopsy tissue. Chronic cough patients also underwent cough reflex sensitivity testing using citric acid. RESULTS: There was no significant difference in incidence of infection between healthy volunteers and chronic cough patients (p = 0.115) or non-lymphocytic and lymphocytic groups (p = 0.404). BAL cell percentages were not significantly different between healthy volunteers and chronic cough patients without lymphocytosis. Lymphocytic patients however had a significantly raised percentage of lymphocytes (p < 0.01), neutrophils (p < 0.05), eosinophils (p < 0.05) and decreased macrophages (p < 0.001) verses healthy volunteers. There was no significant difference in the cough reflex sensitivity between non-lymphocytic and lymphocytic patients (p = 0.536). CONCLUSIONS: This study indicates latent infection in the lung is unlikely to play an important role in chronic cough, but a role for undetected or undetectable pathogens in either the lung or a distal site could not be ruled out. TRIALS REGISTRATION: Current Controlled Trials ISRCTN62337037 & ISRCTN40147207",2012 Sep 14,"['West, Peter W', 'Kelsall, Angela', 'Decalmer, Samantha', 'Dove, Winifred', 'Bishop, Paul W', 'Stewart, James P', 'Woodcock, Ashley A', 'Smith, Jaclyn A']",Cough,,,True
8c5bd7a3606dc60cc568fb2614c8a5bdc00bffbb,PMC,PCR based bronchoscopic detection of common respiratory pathogens in chronic cough: a case control study,http://dx.doi.org/10.1186/1745-9974-8-5,PMC3496690,22978556,CC BY,"BACKGROUND: Viral respiratory tract infection is the most frequent cause of acute cough and is reported at onset in about one third of patients with chronic cough. Persistent infection is therefore one possible explanation for the cough reflex hypersensitivity and pulmonary inflammation reported in chronic cough patients. METHODS: Bronchoscopic endobronchial biopsies and bronchoalveolar lavage cell counts were obtained from ten healthy volunteers and twenty treatment resistant chronic cough patients (10 selected for lavage lymphocytosis). A screen for known respiratory pathogens was performed on biopsy tissue. Chronic cough patients also underwent cough reflex sensitivity testing using citric acid. RESULTS: There was no significant difference in incidence of infection between healthy volunteers and chronic cough patients (p = 0.115) or non-lymphocytic and lymphocytic groups (p = 0.404). BAL cell percentages were not significantly different between healthy volunteers and chronic cough patients without lymphocytosis. Lymphocytic patients however had a significantly raised percentage of lymphocytes (p < 0.01), neutrophils (p < 0.05), eosinophils (p < 0.05) and decreased macrophages (p < 0.001) verses healthy volunteers. There was no significant difference in the cough reflex sensitivity between non-lymphocytic and lymphocytic patients (p = 0.536). CONCLUSIONS: This study indicates latent infection in the lung is unlikely to play an important role in chronic cough, but a role for undetected or undetectable pathogens in either the lung or a distal site could not be ruled out. TRIALS REGISTRATION: Current Controlled Trials ISRCTN62337037 & ISRCTN40147207",2012 Sep 14,"['West, Peter W', 'Kelsall, Angela', 'Decalmer, Samantha', 'Dove, Winifred', 'Bishop, Paul W', 'Stewart, James P', 'Woodcock, Ashley A', 'Smith, Jaclyn A']",Cough,,,True
2ad78e3c71255e44a415f1e3c933ba418f19c4ee,PMC,PCR based bronchoscopic detection of common respiratory pathogens in chronic cough: a case control study,http://dx.doi.org/10.1186/1745-9974-8-5,PMC3496690,22978556,CC BY,"BACKGROUND: Viral respiratory tract infection is the most frequent cause of acute cough and is reported at onset in about one third of patients with chronic cough. Persistent infection is therefore one possible explanation for the cough reflex hypersensitivity and pulmonary inflammation reported in chronic cough patients. METHODS: Bronchoscopic endobronchial biopsies and bronchoalveolar lavage cell counts were obtained from ten healthy volunteers and twenty treatment resistant chronic cough patients (10 selected for lavage lymphocytosis). A screen for known respiratory pathogens was performed on biopsy tissue. Chronic cough patients also underwent cough reflex sensitivity testing using citric acid. RESULTS: There was no significant difference in incidence of infection between healthy volunteers and chronic cough patients (p = 0.115) or non-lymphocytic and lymphocytic groups (p = 0.404). BAL cell percentages were not significantly different between healthy volunteers and chronic cough patients without lymphocytosis. Lymphocytic patients however had a significantly raised percentage of lymphocytes (p < 0.01), neutrophils (p < 0.05), eosinophils (p < 0.05) and decreased macrophages (p < 0.001) verses healthy volunteers. There was no significant difference in the cough reflex sensitivity between non-lymphocytic and lymphocytic patients (p = 0.536). CONCLUSIONS: This study indicates latent infection in the lung is unlikely to play an important role in chronic cough, but a role for undetected or undetectable pathogens in either the lung or a distal site could not be ruled out. TRIALS REGISTRATION: Current Controlled Trials ISRCTN62337037 & ISRCTN40147207",2012 Sep 14,"['West, Peter W', 'Kelsall, Angela', 'Decalmer, Samantha', 'Dove, Winifred', 'Bishop, Paul W', 'Stewart, James P', 'Woodcock, Ashley A', 'Smith, Jaclyn A']",Cough,,,False
062d0779c4b304f4188666a3989152d9f9557340,PMC,High Content Image Based Analysis Identifies Cell Cycle Inhibitors as Regulators of Ebola Virus Infection,http://dx.doi.org/10.3390/v4101865,PMC3497033,23202445,CC BY,"Viruses modulate a number of host biological responses including the cell cycle to favor their replication. In this study, we developed a high-content imaging (HCI) assay to measure DNA content and identify different phases of the cell cycle. We then investigated the potential effects of cell cycle arrest on Ebola virus (EBOV) infection. Cells arrested in G1 phase by serum starvation or G1/S phase using aphidicolin or G2/M phase using nocodazole showed much reduced EBOV infection compared to the untreated control. Release of cells from serum starvation or aphidicolin block resulted in a time-dependent increase in the percentage of EBOV infected cells. The effect of EBOV infection on cell cycle progression was found to be cell-type dependent. Infection of asynchronous MCF-10A cells with EBOV resulted in a reduced number of cells in G2/M phase with concomitant increase of cells in G1 phase. However, these effects were not observed in HeLa or A549 cells. Together, our studies suggest that EBOV requires actively proliferating cells for efficient replication. Furthermore, multiplexing of HCI based assays to detect viral infection, cell cycle status and other phenotypic changes in a single cell population will provide useful information during screening campaigns using siRNA and small molecule therapeutics.",2012 Sep 25,"['Kota, Krishna P.', 'Benko, Jacqueline G.', 'Mudhasani, Rajini', 'Retterer, Cary', 'Tran, Julie P.', 'Bavari, Sina', 'Panchal, Rekha G.']",Viruses,,,True
7d0c3cb7b6d6dfcb416028248132542c99f80ba0,PMC,Forty-Five Years of Marburg Virus Research,http://dx.doi.org/10.3390/v4101878,PMC3497034,23202446,CC BY,"In 1967, the first reported filovirus hemorrhagic fever outbreak took place in Germany and the former Yugoslavia. The causative agent that was identified during this outbreak, Marburg virus, is one of the most deadly human pathogens. This article provides a comprehensive overview of our current knowledge about Marburg virus disease ranging from ecology to pathogenesis and molecular biology.",2012 Oct 1,"['Brauburger, Kristina', 'Hume, Adam J.', 'Mühlberger, Elke', 'Olejnik, Judith']",Viruses,,,True
06e89cafce095f075c8a197fbdfb78c259133a8b,PMC,Pathogenesis of Lassa Fever,http://dx.doi.org/10.3390/v4102031,PMC3497040,23202452,CC BY,"Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host’s immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents.",2012 Oct 9,"['Yun, Nadezhda E.', 'Walker, David H.']",Viruses,,,True
f1d308db379b3c293bcfc8fe251c043fe8842358,PMC,Serological Assays Based on Recombinant Viral Proteins for the Diagnosis of Arenavirus Hemorrhagic Fevers,http://dx.doi.org/10.3390/v4102097,PMC3497043,23202455,CC BY,"The family Arenaviridae, genus Arenavirus, consists of two phylogenetically independent groups: Old World (OW) and New World (NW) complexes. The Lassa and Lujo viruses in the OW complex and the Guanarito, Junin, Machupo, Sabia, and Chapare viruses in the NW complex cause viral hemorrhagic fever (VHF) in humans, leading to serious public health concerns. These viruses are also considered potential bioterrorism agents. Therefore, it is of great importance to detect these pathogens rapidly and specifically in order to minimize the risk and scale of arenavirus outbreaks. However, these arenaviruses are classified as BSL-4 pathogens, thus making it difficult to develop diagnostic techniques for these virus infections in institutes without BSL-4 facilities. To overcome these difficulties, antibody detection systems in the form of an enzyme-linked immunosorbent assay (ELISA) and an indirect immunofluorescence assay were developed using recombinant nucleoproteins (rNPs) derived from these viruses. Furthermore, several antigen-detection assays were developed. For example, novel monoclonal antibodies (mAbs) to the rNPs of Lassa and Junin viruses were generated. Sandwich antigen-capture (Ag-capture) ELISAs using these mAbs as capture antibodies were developed and confirmed to be sensitive and specific for detecting the respective arenavirus NPs. These rNP-based assays were proposed to be useful not only for an etiological diagnosis of VHFs, but also for seroepidemiological studies on VHFs. We recently developed arenavirus neutralization assays using vesicular stomatitis virus (VSV)-based pseudotypes bearing arenavirus recombinant glycoproteins. The goal of this article is to review the recent advances in developing laboratory diagnostic assays based on recombinant viral proteins for the diagnosis of VHFs and epidemiological studies on the VHFs caused by arenaviruses.",2012 Oct 12,"['Fukushi, Shuetsu', 'Tani, Hideki', 'Yoshikawa, Tomoki', 'Saijo, Masayuki', 'Morikawa, Shigeru']",Viruses,,,True
12c7bde10bc2422a099a326c99cba1ec1e496431,PMC,D471G Mutation in LCMV-NP Affects its Ability to Self-associate and Results in a Dominant Negative Effect in Viral RNA Synthesis,http://dx.doi.org/10.3390/v4102137,PMC3497045,23202457,CC BY,"Arenaviruses merit significant interest because several family members are etiological agents of severe hemorrhagic fevers, representing a major burden to public health. Currently, there are no FDA-licensed vaccines against arenaviruses and the only available antiviral therapy is limited to the use of ribavirin that is partially effective. Arenavirus nucleoprotein (NP) is found associated with the genomic RNA forming the viral ribonucleoproteins (vRNPs) that together with the polymerase (L) direct viral replication and transcription. Virion formation requires the recruitment of vRNPs into budding sites, a process in which the arenavirus matrix-like protein (Z) plays a major role. Therefore, proper NP-NP and NP-Z interactions are required for the generation of infectious progeny. In this work we demonstrate the role of the amino acid residue D471 in the self-association of lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP). Amino acid substitutions at this position abrogate NP oligomerization, affecting its ability to mediate replication and transcription of a minigenome reporter plasmid. However, its ability to interact with the Z protein, counteract the cellular interferon response and bind to dsRNA analogs was retained. Additionally, we also document the dominant negative effect of D471G mutation on viral infection, suggesting that NP self-association is an excellent target for the development of new antivirals against arenaviruses.",2012 Oct 16,"['Ortiz-Riaño, Emilio', 'Cheng, Benson Y. H.', 'de la Torre, Juan C.', 'Martínez-Sobrido, Luis']",Viruses,,,True
33bee45e93ec92d0813e39a07e158605af679215,PMC,Hepatitis C Virus and Cellular Stress Response: Implications to Molecular Pathogenesis of Liver Diseases,http://dx.doi.org/10.3390/v4102251,PMC3497051,23202463,CC BY,"Infection with hepatitis C virus (HCV) is a leading risk factor for chronic liver disease progression, including steatosis, cirrhosis, and hepatocellular carcinoma. With approximately 3% of the human population infected worldwide, HCV infection remains a global public health challenge. The efficacy of current therapy is still limited in many patients infected with HCV, thus a greater understanding of pathogenesis in HCV infection is desperately needed. Emerging lines of evidence indicate that HCV triggers a wide range of cellular stress responses, including cell cycle arrest, apoptosis, endoplasmic reticulum (ER) stress/unfolded protein response (UPR), and autophagy. Also, recent studies suggest that these HCV-induced cellular responses may contribute to chronic liver diseases by modulating cell proliferation, altering lipid metabolism, and potentiating oncogenic pathways. However, the molecular mechanism underlying HCV infection in the pathogenesis of chronic liver diseases still remains to be determined. Here, we review the known stress response activation in HCV infection in vitro and in vivo, and also explore the possible relationship of a variety of cellular responses with the pathogenicity of HCV-associated diseases. Comprehensive knowledge of HCV-mediated disease progression shall shed new insights into the discovery of novel therapeutic targets and the development of new intervention strategy.",2012 Oct 19,"['Ke, Po-Yuan', 'Chen, Steve S.-L.']",Viruses,,,True
e42f45097fff6577e1ba2da76661b56f7bff299a,PMC,Fragment-Based Screening by Protein Crystallography: Successes and Pitfalls,http://dx.doi.org/10.3390/ijms131012857,PMC3497300,23202926,CC BY,"Fragment-based drug discovery (FBDD) concerns the screening of low-molecular weight compounds against macromolecular targets of clinical relevance. These compounds act as starting points for the development of drugs. FBDD has evolved and grown in popularity over the past 15 years. In this paper, the rationale and technology behind the use of X-ray crystallography in fragment based screening (FBS) will be described, including fragment library design and use of synchrotron radiation and robotics for high-throughput X-ray data collection. Some recent uses of crystallography in FBS will be described in detail, including interrogation of the drug targets β-secretase, phenylethanolamine N-methyltransferase, phosphodiesterase 4A and Hsp90. These examples provide illustrations of projects where crystallography is straightforward or difficult, and where other screening methods can help overcome the limitations of crystallography necessitated by diffraction quality.",2012 Oct 8,"['Chilingaryan, Zorik', 'Yin, Zhou', 'Oakley, Aaron J.']",Int J Mol Sci,,,True
9bbac1f67fbab1d4f3e9a20387a63989bf40bfad,PMC,Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies,http://dx.doi.org/10.3390/ijms131013438,PMC3497335,23202961,CC BY,"Multiple sclerosis, the clinical features and pathological correlate for which were first described by Charcot, is a chronic neuroinflammatory disease with unknown etiology and variable clinical evolution. Although neuroinflammation is a descriptive denominator in multiple sclerosis based on histopathological observations, namely the penetration of leukocytes into the central nervous system, the clinical symptoms of relapses, remissions and progressive paralysis are the result of losses of myelin and neurons. In the absence of etiological factors as targets for prevention and therapy, the definition of molecular mechanisms that form the basis of inflammation, demyelination and toxicity for neurons have led to a number of treatments that slow down disease progression in specific patient cohorts, but that do not cure the disease. Current therapies are directed to block the immune processes, both innate and adaptive, that are associated with multiple sclerosis. In this review, we analyze the role of cytokines in the multiple sclerosis pathogenesis and current/future use of them in treatments of multiple sclerosis.",2012 Oct 19,"['Amedei, Amedeo', 'Prisco, Domenico', 'D’Elios, Mario Milco']",Int J Mol Sci,,,True
cb55f63de6946c57d21275e45c94c79955bba977,PMC,The Criteria to Confirm the Role of Epstein-Barr Virus in Nasopharyngeal Carcinoma Initiation,http://dx.doi.org/10.3390/ijms131013737,PMC3497352,23202978,CC BY,"Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC), but it remains obscure whether EBV is a viral cause of, or only an accompaniment of, NPC. We will discuss the accumulated evidence pointing to the relationship between EBV infection and NPC initiation from epidemiologic, pathogenic, molecular oncogenic, and experimental animal studies. We believe that convincing evidence from these perspectives must be provided before we can ascertain the causal role of EBV infection in NPC. Specifically, (1) epidemiological studies should reveal EBV infection as a risk factor; (2) the introduction of EBV into an animal model should produce NPC; (3) in the animal model NPC, the main molecular event(s) or the involved signaling pathway(s) should be identical to that in human NPC; and (4) finally and most importantly, prevention of EBV infection or clearance of EBV from infected individuals must be able to reduce the incidence rate of NPC.",2012 Oct 23,"['Gu, Ai-Di', 'Zeng, Mu-Sheng', 'Qian, Chao-Nan']",Int J Mol Sci,,,True
cc5ffabf819570a8912666ecdb9de62cb48e0387,PMC,Equivalence of Self- and Staff-Collected Nasal Swabs for the Detection of Viral Respiratory Pathogens,http://dx.doi.org/10.1371/journal.pone.0048508,PMC3498275,23155387,CC BY,"BACKGROUND: The need for the timely collection of diagnostic biosamples during symptomatic episodes represents a major obstacle to large-scale studies on acute respiratory infection (ARI) epidemiology. This may be circumvented by having the participants collect their own nasal swabs. We compared self- and staff-collected swabs in terms of swabbing quality and detection of viral respiratory pathogens. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a prospective study among employees of our institution during the ARI season 2010/2011 (December-March). Weekly emails were sent to the participants (n = 84), reminding them to come to the study center in case of new symptoms. The participants self-collected an anterior nasal swab from one nostril, and trained study personnel collected one from the other nostril. The participants self-collected another two swabs (one from each nostril) on a subsequent day. Human β-actin DNA concentration was determined in the swabs as a quality control. Viral respiratory pathogens were detected by multiplex RT-PCR (Seeplex RV15 kit, Seegene, Eschborn, Germany). Of 84 participants, 56 (67%) reported at least one ARI episode, 18 participants two, and one participant three. Self-swabbing was highly accepted by the participants. The amount of β-actin DNA per swab was higher in the self- than in the staff-collected swabs (p = 0.008). β-actin concentration was lower in the self-swabs collected on day 1 than in those collected on a subsequent day (p<0.0001). A respiratory viral pathogen was detected in 31% (23/75) of staff- and in 35% (26/75) of self-collected swabs (p = 0.36). With both approaches, the most frequently identified pathogens were human rhinoviruses A/B/C (12/75 swabs, 16%) and human coronavirus OC43 (4/75 swabs, 5%). There was almost perfect agreement between self- and staff-collected swabs in terms of pathogen detection (agreement = 93%, kappa = 0.85, p<0.0001). CONCLUSIONS/SIGNIFICANCE: Nasal self-swabbing for identification of viral ARI pathogens proved to be equivalent to staff-swabbing in this population in terms of acceptance and pathogen detection.",2012 Nov 14,"['Akmatov, Manas K.', 'Gatzemeier, Anja', 'Schughart, Klaus', 'Pessler, Frank']",PLoS One,,,True
16fb795aec2acb8b86ddac119772abde6392d40f,PMC,Ribosomal frameshifting used in influenza A virus expression occurs within the sequence UCC_UUU_CGU and is in the +1 direction,http://dx.doi.org/10.1098/rsob.120109,PMC3498833,23155484,CC BY,"Programmed ribosomal frameshifting is used in the expression of many virus genes and some cellular genes. In eukaryotic systems, the most well-characterized mechanism involves –1 tandem tRNA slippage on an X_XXY_YYZ motif. By contrast, the mechanisms involved in programmed +1 (or −2) slippage are more varied and often poorly characterized. Recently, a novel gene, PA-X, was discovered in influenza A virus and found to be expressed via a shift to the +1 reading frame. Here, we identify, by mass spectrometric analysis, both the site (UCC_UUU_CGU) and direction (+1) of the frameshifting that is involved in PA-X expression. Related sites are identified in other virus genes that have previously been proposed to be expressed via +1 frameshifting. As these viruses infect insects (chronic bee paralysis virus), plants (fijiviruses and amalgamaviruses) and vertebrates (influenza A virus), such motifs may form a new class of +1 frameshift-inducing sequences that are active in diverse eukaryotes.",2012 Oct,"['Firth, A. E.', 'Jagger, B. W.', 'Wise, H. M.', 'Nelson, C. C.', 'Parsawar, K.', 'Wills, N. M.', 'Napthine, S.', 'Taubenberger, J. K.', 'Digard, P.', 'Atkins, J. F.']",Open Biol,,,True
d014a65d8069ebac6e33bc8bc4dba674151e07d7,PMC,18S rRNA is a reliable normalisation gene for real time PCR based on influenza virus infected cells,http://dx.doi.org/10.1186/1743-422X-9-230,PMC3499178,23043930,CC BY,"BACKGROUND: One requisite of quantitative reverse transcription PCR (qRT-PCR) is to normalise the data with an internal reference gene that is invariant regardless of treatment, such as virus infection. Several studies have found variability in the expression of commonly used housekeeping genes, such as beta-actin (ACTB) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), under different experimental settings. However, ACTB and GAPDH remain widely used in the studies of host gene response to virus infections, including influenza viruses. To date no detailed study has been described that compares the suitability of commonly used housekeeping genes in influenza virus infections. The present study evaluated several commonly used housekeeping genes [ACTB, GAPDH, 18S ribosomal RNA (18S rRNA), ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide (ATP5B) and ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9) (ATP5G1)] to identify the most stably expressed gene in human, pig, chicken and duck cells infected with a range of influenza A virus subtypes. RESULTS: The relative expression stability of commonly used housekeeping genes were determined in primary human bronchial epithelial cells (HBECs), pig tracheal epithelial cells (PTECs), and chicken and duck primary lung-derived cells infected with five influenza A virus subtypes. Analysis of qRT-PCR data from virus and mock infected cells using NormFinder and BestKeeper software programmes found that 18S rRNA was the most stable gene in HBECs, PTECs and avian lung cells. CONCLUSIONS: Based on the presented data from cell culture models (HBECs, PTECs, chicken and duck lung cells) infected with a range of influenza viruses, we found that 18S rRNA is the most stable reference gene for normalising qRT-PCR data. Expression levels of the other housekeeping genes evaluated in this study (including ACTB and GPADH) were highly affected by influenza virus infection and hence are not reliable as reference genes for RNA normalisation.",2012 Oct 8,"['Kuchipudi, Suresh V', 'Tellabati, Meenu', 'Nelli, Rahul K', 'White, Gavin A', 'Perez, Belinda Baquero', 'Sebastian, Sujith', 'Slomka, Marek J', 'Brookes, Sharon M', 'Brown, Ian H', 'Dunham, Stephen P', 'Chang, Kin-Chow']",Virol J,,,True
9fb9a39c7e68fd9c32ab53a6a6ce9af6f1fd2e09,PMC,The Human Cytomegalovirus DNA Polymerase Processivity Factor UL44 Is Modified by SUMO in a DNA-Dependent Manner,http://dx.doi.org/10.1371/journal.pone.0049630,PMC3499415,23166733,CC BY,"During the replication of human cytomegalovirus (HCMV) genome, the viral DNA polymerase subunit UL44 plays a key role, as by binding both DNA and the polymerase catalytic subunit it confers processivity to the holoenzyme. However, several lines of evidence suggest that UL44 might have additional roles during virus life cycle. To shed light on this, we searched for cellular partners of UL44 by yeast two-hybrid screenings. Intriguingly, we discovered the interaction of UL44 with Ubc9, an enzyme involved in the covalent conjugation of SUMO (Small Ubiquitin-related MOdifier) to cellular and viral proteins. We found that UL44 can be extensively sumoylated not only in a cell-free system and in transfected cells, but also in HCMV-infected cells, in which about 50% of the protein resulted to be modified at late times post-infection, when viral genome replication is accomplished. Mass spectrometry studies revealed that UL44 possesses multiple SUMO target sites, located throughout the protein. Remarkably, we observed that binding of UL44 to DNA greatly stimulates its sumoylation both in vitro and in vivo. In addition, we showed that overexpression of SUMO alters the intranuclear distribution of UL44 in HCMV-infected cells, and enhances both virus production and DNA replication, arguing for an important role for sumoylation in HCMV life cycle and UL44 function(s). These data report for the first time the sumoylation of a viral processivity factor and show that there is a functional interplay between the HCMV UL44 protein and the cellular sumoylation system.",2012 Nov 15,"['Sinigalia, Elisa', 'Alvisi, Gualtiero', 'Segré, Chiara V.', 'Mercorelli, Beatrice', 'Muratore, Giulia', 'Winkler, Michael', 'Hsiao, He-Hsuan', 'Urlaub, Henning', 'Ripalti, Alessandro', 'Chiocca, Susanna', 'Palù, Giorgio', 'Loregian, Arianna']",PLoS One,,,True
24e84b0b2c9242ecdddf63700da1454c7aa0efe3,PMC,The Human Cytomegalovirus DNA Polymerase Processivity Factor UL44 Is Modified by SUMO in a DNA-Dependent Manner,http://dx.doi.org/10.1371/journal.pone.0049630,PMC3499415,23166733,CC BY,"During the replication of human cytomegalovirus (HCMV) genome, the viral DNA polymerase subunit UL44 plays a key role, as by binding both DNA and the polymerase catalytic subunit it confers processivity to the holoenzyme. However, several lines of evidence suggest that UL44 might have additional roles during virus life cycle. To shed light on this, we searched for cellular partners of UL44 by yeast two-hybrid screenings. Intriguingly, we discovered the interaction of UL44 with Ubc9, an enzyme involved in the covalent conjugation of SUMO (Small Ubiquitin-related MOdifier) to cellular and viral proteins. We found that UL44 can be extensively sumoylated not only in a cell-free system and in transfected cells, but also in HCMV-infected cells, in which about 50% of the protein resulted to be modified at late times post-infection, when viral genome replication is accomplished. Mass spectrometry studies revealed that UL44 possesses multiple SUMO target sites, located throughout the protein. Remarkably, we observed that binding of UL44 to DNA greatly stimulates its sumoylation both in vitro and in vivo. In addition, we showed that overexpression of SUMO alters the intranuclear distribution of UL44 in HCMV-infected cells, and enhances both virus production and DNA replication, arguing for an important role for sumoylation in HCMV life cycle and UL44 function(s). These data report for the first time the sumoylation of a viral processivity factor and show that there is a functional interplay between the HCMV UL44 protein and the cellular sumoylation system.",2012 Nov 15,"['Sinigalia, Elisa', 'Alvisi, Gualtiero', 'Segré, Chiara V.', 'Mercorelli, Beatrice', 'Muratore, Giulia', 'Winkler, Michael', 'Hsiao, He-Hsuan', 'Urlaub, Henning', 'Ripalti, Alessandro', 'Chiocca, Susanna', 'Palù, Giorgio', 'Loregian, Arianna']",PLoS One,,,False
efa871aeaf22cbd0ce30e8bd1cb3d1afff2a98f9,PMC,Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus,http://dx.doi.org/10.1371/journal.pone.0048702,PMC3499507,23166591,CC BY,"The trans-activator Tat protein is a viral regulatory protein essential for HIV-1 replication. Tat trafficks to the nucleoplasm and the nucleolus. The nucleolus, a highly dynamic and structured membrane-less sub-nuclear compartment, is the site of rRNA and ribosome biogenesis and is involved in numerous cellular functions including transcriptional regulation, cell cycle control and viral infection. Importantly, transient nucleolar trafficking of both Tat and HIV-1 viral transcripts are critical in HIV-1 replication, however, the role(s) of the nucleolus in HIV-1 replication remains unclear. To better understand how the interaction of Tat with the nucleolar machinery contributes to HIV-1 pathogenesis, we investigated the quantitative changes in the composition of the nucleolar proteome of Jurkat T-cells stably expressing HIV-1 Tat fused to a TAP tag. Using an organellar proteomic approach based on mass spectrometry, coupled with Stable Isotope Labelling in Cell culture (SILAC), we quantified 520 proteins, including 49 proteins showing significant changes in abundance in Jurkat T-cell nucleolus upon Tat expression. Numerous proteins exhibiting a fold change were well characterised Tat interactors and/or known to be critical for HIV-1 replication. This suggests that the spatial control and subcellular compartimentaliation of these cellular cofactors by Tat provide an additional layer of control for regulating cellular machinery involved in HIV-1 pathogenesis. Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. We present here the first differential profiling of the nucleolar proteome of T-cells expressing HIV-1 Tat. We discuss how these proteins collectively participate in interconnected networks converging to adapt the nucleolus dynamic activities, which favor host biosynthetic activities and may contribute to create a cellular environment supporting robust HIV-1 production.",2012 Nov 15,"['Jarboui, Mohamed Ali', 'Bidoia, Carlo', 'Woods, Elena', 'Roe, Barbara', 'Wynne, Kieran', 'Elia, Giuliano', 'Hall, William W.', 'Gautier, Virginie W.']",PLoS One,,,True
8597d9f2e677de02b0166ad69f8045b979b3a82a,PMC,Role of Human Sec63 in Modulating the Steady-State Levels of Multi-Spanning Membrane Proteins,http://dx.doi.org/10.1371/journal.pone.0049243,PMC3499540,23166619,CC BY,"The Sec61 translocon of the endoplasmic reticulum (ER) membrane forms an aqueous pore, allowing polypeptides to be transferred across or integrated into membranes. Protein translocation into the ER can occur co- and posttranslationally. In yeast, posttranslational translocation involves the heptameric translocase complex including its Sec62p and Sec63p subunits. The mammalian ER membrane contains orthologs of yeast Sec62p and Sec63p, but their function is poorly understood. Here, we analyzed the effects of excess and deficit Sec63 on various ER cargoes using human cell culture systems. The overexpression of Sec63 reduces the steady-state levels of viral and cellular multi-spanning membrane proteins in a cotranslational mode, while soluble and single-spanning ER reporters are not affected. Consistent with this, the knock-down of Sec63 increases the steady-state pools of polytopic ER proteins, suggesting a substrate-specific and regulatory function of Sec63 in ER import. Overexpressed Sec63 exerts its down-regulating activity on polytopic protein levels independent of its Sec62-interacting motif, indicating that it may not act in conjunction with Sec62 in human cells. The specific action of Sec63 is further sustained by our observations that the up-regulation of either Sec62 or two other ER proteins with lumenal J domains, like ERdj1 and ERdj4, does not compromise the steady-state level of a multi-spanning membrane reporter. A J domain-specific mutation of Sec63, proposed to weaken its interaction with the ER resident BiP chaperone, reduces the down-regulating capacity of excess Sec63, suggesting an involvement of BiP in this process. Together, these results suggest that Sec63 may perform a substrate-selective quantity control function during cotranslational ER import.",2012 Nov 15,"['Mades, Andreas', 'Gotthardt, Katherina', 'Awe, Karin', 'Stieler, Jens', 'Döring, Tatjana', 'Füser, Sabine', 'Prange, Reinhild']",PLoS One,,,True
b09362a1f23af2b6603e7b92b58003b7f9719840,PMC,Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates,http://dx.doi.org/10.1371/journal.pone.0049265,PMC3499546,23166625,CC BY,"Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.",2012 Nov 15,"['Zhang, Zhao', 'Liu, Jun', 'Li, Meng', 'Yang, Hui', 'Zhang, Chiyu']",PLoS One,,,True
a4b5258ac97a71a862ce4098a819d37bdec19190,PMC,Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates,http://dx.doi.org/10.1371/journal.pone.0049265,PMC3499546,23166625,CC BY,"Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.",2012 Nov 15,"['Zhang, Zhao', 'Liu, Jun', 'Li, Meng', 'Yang, Hui', 'Zhang, Chiyu']",PLoS One,,,False
b097bead51cf543bb12eff8d3e0b9acbba67c041,PMC,Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates,http://dx.doi.org/10.1371/journal.pone.0049265,PMC3499546,23166625,CC BY,"Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.",2012 Nov 15,"['Zhang, Zhao', 'Liu, Jun', 'Li, Meng', 'Yang, Hui', 'Zhang, Chiyu']",PLoS One,,,False
ec656117399c96aeb848a626967bf860722bac67,PMC,Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates,http://dx.doi.org/10.1371/journal.pone.0049265,PMC3499546,23166625,CC BY,"Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.",2012 Nov 15,"['Zhang, Zhao', 'Liu, Jun', 'Li, Meng', 'Yang, Hui', 'Zhang, Chiyu']",PLoS One,,,False
679af2e570eda977721a977e3b542b6cd2eafa09,PMC,Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates,http://dx.doi.org/10.1371/journal.pone.0049265,PMC3499546,23166625,CC BY,"Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.",2012 Nov 15,"['Zhang, Zhao', 'Liu, Jun', 'Li, Meng', 'Yang, Hui', 'Zhang, Chiyu']",PLoS One,,,False
8d581519c2e082ec871aeb8e6486e3195111b6b7,PMC,Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates,http://dx.doi.org/10.1371/journal.pone.0049265,PMC3499546,23166625,CC BY,"Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.",2012 Nov 15,"['Zhang, Zhao', 'Liu, Jun', 'Li, Meng', 'Yang, Hui', 'Zhang, Chiyu']",PLoS One,,,False
f353ee74fe20d3333b783fe703231d1313c89303,PMC,Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates,http://dx.doi.org/10.1371/journal.pone.0049265,PMC3499546,23166625,CC BY,"Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.",2012 Nov 15,"['Zhang, Zhao', 'Liu, Jun', 'Li, Meng', 'Yang, Hui', 'Zhang, Chiyu']",PLoS One,,,False
49e18956b9fad9e6114912a46567cdc6b9555c02,PMC,Current Approaches on Viral Infection: Proteomics and Functional Validations,http://dx.doi.org/10.3389/fmicb.2012.00393,PMC3499792,23162545,CC BY,"Viruses could manipulate cellular machinery to ensure their continuous survival and thus become parasites of living organisms. Delineation of sophisticated host responses upon virus infection is a challenging task. It lies in identifying the repertoire of host factors actively involved in the viral infectious cycle and characterizing host responses qualitatively and quantitatively during viral pathogenesis. Mass spectrometry based proteomics could be used to efficiently study pathogen-host interactions and virus-hijacked cellular signaling pathways. Moreover, direct host and viral responses upon infection could be further investigated by activity-based functional validation studies. These approaches involve drug inhibition of secretory pathway, immunofluorescence staining, dominant negative mutant of protein target, real-time PCR, small interfering siRNA-mediated knockdown, and molecular cloning studies. In this way, functional validation could gain novel insights into the high-content proteomic dataset in an unbiased and comprehensive way.",2012 Nov 16,"['Zheng, Jie', 'Tan, Boon Huan', 'Sugrue, Richard', 'Tang, Kai']",Front Microbiol,,,True
3d1d14a7dc9189add63df0501822830a3291a850,PMC,Genomic Sequences of two Novel Levivirus Single-Stranded RNA Coliphages (Family Leviviridae): Evidence for Recombinationin Environmental Strains,http://dx.doi.org/10.3390/v4091548,PMC3499819,23170172,CC BY,"Bacteriophages are likely the most abundant entities in the aquatic environment, yet knowledge of their ecology is limited. During a fecal source-tracking study, two genetically novel Leviviridae strains were discovered. Although the novel strains were isolated from coastal waters 1130 km apart (North Carolina and Rhode Island, USA), these strains shared 97% nucleotide similarity and 97–100% amino acid similarity. When the novel strains were compared to nine Levivirus genogroup I strains, they shared 95–100% similarity among the maturation, capsid and lysis proteins, but only 84–85% in the RNA-dependent RNA polymerase gene. Further bioinformatic analyses suggested a recombination event occurred. To the best of our knowledge, this is the first description of viral recombinants in environmental Leviviridae ssRNA bacteriophages.",2012 Sep 13,"['Friedman, Stephanie D.', 'Snellgrove, Wyatt C.', 'Genthner, Fred J.']",Viruses,,,True
d806b5203cfba5a87c9a39a25d953572eacf9ab9,PMC,Filovirus Research in Gabon and Equatorial Africa: The Experience of a Research Center in the Heart of Africa,http://dx.doi.org/10.3390/v4091592,PMC3499821,23170174,CC BY,"Health research programs targeting the population of Gabon and Equatorial Africa at the International Center for Medical Research in Franceville (CIRMF), Gabon, have evolved during the years since its inception in 1979 in accordance with emerging diseases. Since the reemergence of Ebola virus in Central Africa, the CIRMF “Emerging Viral Disease Unit” developed diagnostic tools and epidemiologic strategies and transfers of such technology to support the response of the National Public Health System and the World Health Organization to epidemics of Ebola virus disease. The Unit carries out a unique investigation program on the natural history of the filoviruses, emergence of epidemics, and Ebola virus pathogenesis. In addition, academic training is provided at all levels to regional and international students covering emerging conditions (host factors, molecular biology, genetics) that favor the spread of viral diseases.",2012 Sep 13,"['Leroy, Eric', 'Gonzalez, Jean Paul']",Viruses,,,True
c75994b5485339cdf4180bedab58e60366e49740,PMC,Potential Vaccines and Post-Exposure Treatments for Filovirus Infections,http://dx.doi.org/10.3390/v4091619,PMC3499823,23170176,CC BY,"Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed.",2012 Sep 21,"['Friedrich, Brian M.', 'Trefry, John C.', 'Biggins, Julia E.', 'Hensley, Lisa E.', 'Honko, Anna N.', 'Smith, Darci R.', 'Olinger, Gene G.']",Viruses,,,True
f4f75af02b7226c5b2363de1a75821a4b9b20412,PMC,Neutralization Interfering Antibodies: A “Novel” Example of Humoral Immune Dysfunction Facilitating Viral Escape?,http://dx.doi.org/10.3390/v4091731,PMC3499828,23170181,CC BY,"The immune response against some viral pathogens, in particular those causing chronic infections, is often ineffective notwithstanding a robust humoral neutralizing response. Several evasion mechanisms capable of subverting the activity of neutralizing antibodies (nAbs) have been described. Among them, the elicitation of non-neutralizing and interfering Abs has been hypothesized. Recently, this evasion mechanism has acquired an increasing interest given its possible impact on novel nAb-based antiviral therapeutic and prophylactic approaches. In this review, we illustrate the mechanisms of Ab-mediated interference and the viral pathogens described in literature as able to adopt this “novel” evasion strategy.",2012 Sep 24,"['Nicasio, Mancini', 'Sautto, Giuseppe', 'Clementi, Nicola', 'Diotti, Roberta A.', 'Criscuolo, Elena', 'Castelli, Matteo', 'Solforosi, Laura', 'Clementi, Massimo', 'Burioni, Roberto']",Viruses,,,True
ab0550f67f34bd6484d7a24b253c8a3e12759b0f,PMC,Reproductive Number and Serial Interval of the First Wave of Influenza A(H1N1)pdm09 Virus in South Africa,http://dx.doi.org/10.1371/journal.pone.0049482,PMC3500305,23166682,CC BY,"BACKGROUND/OBJECTIVE: Describing transmissibility parameters of past pandemics from diverse geographic sites remains critical to planning responses to future outbreaks. We characterize the transmissibility of influenza A(H1N1)pdm09 (hereafter pH1N1) in South Africa during 2009 by estimating the serial interval (SI), the initial effective reproductive number (initial R(t)) and the temporal variation of R(t). METHODS: We make use of data from a central registry of all pH1N1 laboratory-confirmed cases detected throughout South Africa. Whenever date of symptom onset is missing, we estimate it from the date of specimen collection using a multiple imputation approach repeated 100 times for each missing value. We apply a likelihood-based method (method 1) for simultaneous estimation of initial R(t) and the SI; estimate initial R(t) from SI distributions established from prior field studies (method 2); and the Wallinga and Teunis method (method 3) to model the temporal variation of R(t). RESULTS: 12,360 confirmed pH1N1 cases were reported in the central registry. During the period of exponential growth of the epidemic (June 21 to August 3, 2009), we simultaneously estimate a mean R(t) of 1.47 (95% CI: 1.30–1.72) and mean SI of 2.78 days (95% CI: 1.80–3.75) (method 1). Field studies found a mean SI of 2.3 days between primary cases and laboratory-confirmed secondary cases, and 2.7 days when considering both suspected and confirmed secondary cases. Incorporating the SI estimate from field studies using laboratory-confirmed cases, we found an initial R(t) of 1.43 (95% CI: 1.38–1.49) (method 2). The mean R(t) peaked at 2.91 (95% CI: 0.85–2.91) on June 21, as the epidemic commenced, and R(t)>1 was sustained until August 22 (method 3). CONCLUSIONS: Transmissibility characteristics of pH1N1 in South Africa are similar to estimates reported by countries outside of Africa. Estimations using the likelihood-based method are in agreement with field findings.",2012 Nov 16,"['Archer, Brett N.', 'Tempia, Stefano', 'White, Laura F.', 'Pagano, Marcello', 'Cohen, Cheryl']",PLoS One,,,True
4ec1787f65505b0751777ff1f2cb40d13c0d2b96,PMC,On programmed ribosomal frameshifting: the alternative proteomes,http://dx.doi.org/10.3389/fgene.2012.00242,PMC3500957,23181069,CC BY,"Frameshifting results from two main mechanisms: genomic insertions or deletions (indels) or programmed ribosomal frameshifting. Whereas indels can disrupt normal protein function, programmed ribosomal frameshifting can result in dual-coding genes, each of which can produce multiple functional products. Here, I summarize technical advances that have made it possible to identify programmed ribosomal frameshifting events in a systematic way. The results of these studies suggest that such frameshifting occurs in all genomes, and I will discuss methods that could help characterize the resulting alternative proteomes.",2012 Nov 19,"Ketteler, Robin",Front Genet,,,True
aed3656733b0b5c6f2ad8a14ef5e864d468d66da,PMC,Measuring healthcare preparedness: an all-hazards approach,http://dx.doi.org/10.1186/2045-4015-1-42,PMC3502095,23098101,CC BY,"In a paper appearing in this issue, Adini, et al. describe a struggle familiar to many emergency planners—the challenge of planning for all scenarios. The authors contend that all-hazards, or capabilities-based planning, in which a set of core capabilities applicable to numerous types of events is developed, is a more efficient way to achieve general health care system emergency preparedness than scenario-based planning. Essentially, the core of what is necessary to plan for and respond to one kind of disaster (e.g. a biologic event) is also necessary for planning and responding to other types of disasters, allowing for improvements in planning and maximizing efficiencies. While Adini, et al. have advanced the science of health care emergency preparedness through their consideration of 490 measures to assess preparedness, a shorter set of validated preparedness measures would support the dual goals of accountability and improved outcomes and could provide the basis for determining which actions in the name of preparedness really matter.",2012 Oct 25,"['Marcozzi, David E', 'Lurie, Nicole']",Isr J Health Policy Res,,,True
dc014f8a66864512015686665ebbf01c92d8089e,PMC,A cross-sectional study of pandemic influenza health literacy and the effect of a public health campaign,http://dx.doi.org/10.1186/1756-0500-5-377,PMC3502135,22830499,CC BY,"BACKGROUND: To ascertain the understanding of 2009 pandemic (H1N1) influenza and relevant infection control measures in an emergency department population and to assess the effectiveness of education campaigns in informing the public about the pandemic. METHODS: Questionnaires were administered to patients, visitors, non-clinical staff and volunteers. Data were collected on knowledge, preventative measures, information sources, attitudes to government and media reporting, perceived seriousness, behaviour change and intended compliance with future measures. Results were used to construct an overall knowledge score. RESULTS: There were 252 participants. Traditional forms of mass media (138 [55%]) remained the principal information source. Approximately 70% (176) accurately described mode of transmission and recommended precautions and 68% (175) reported behaviour change because of the pandemic. Gaps in knowledge included failure to identify certain high risk groups. Recall of government campaigns was significantly associated with a higher knowledge score. 60% (151) thought that authorities and media had exaggerated the threat; only 40% (101) would comply with recommended measures in a future pandemic. CONCLUSIONS: The knowledge regarding pandemic influenza was high in this population and positively affected by official campaigns. Pandemic planning should address knowledge gaps and the impression that authorities had exaggerated the public-health threat.",2012 Jul 26,"['Jhummon-Mahadnac, Namrata Devi', 'Knott, Jonathan', 'Marshall, Caroline']",BMC Res Notes,,,True
e2309c084ac694227f0411037944e3829c04c777,PMC,Bovine herpes virus type 1 induces apoptosis through Fas-dependent and mitochondria-controlled manner in Madin-Darby bovine kidney cells,http://dx.doi.org/10.1186/1743-422X-9-202,PMC3502331,22978358,CC BY,"BACKGROUND: Bovine herpesvirus type 1 (BHV-1) is an important pathogen in cattle that is responsible for substantial economic losses. Previous studies suggest that BHV-1 may induce apoptosis in Madin-Darby bovine kidney (MDBK) cells via a mechanism only involving caspases and p53. However, the mechanism for BHV-1-induced MDBK cell apoptosis still requires more research. METHODS: MDBK was used as a model to study the precise signaling pathways of apoptosis induced by BHV-1 infection. RESULTS: BHV-1 infection activated a Fas/FasL-mediated apoptotic pathway, resulting in activation of caspase-8 and cleavage of Bid. In addition, BHV-1 infection down-regulated Bcl-2 and up-regulated Bax expression, thereby initiating the release of cytochrome c followed by caspase-9 activation. The combined activation of the extrinsic and intrinsic pathways resulted in activation of downstream effecter caspase-3 and poly ADP-ribose polymerase (PARP), leading to apoptosis. Furthermore, blocking apoptosis using caspase inhibitors improved BHV-1-infected MDBK cell viability to different extent. BHV-1 infection did not induce significant DNA fragmentation in MDBK cells pretreated with ammonium chloride (NH(4)Cl) or cells infected with UV-inactivated BHV-1. Blocking caspases activation increased BHV-1 replication. CONCLUSIONS: BHV-1 induces apoptosis in MDBK cells through extrinsic and intrinsic pathways and there might be cross-talk between the two pathways. In addition, BHV-1 replication may be necessary for the induction of apoptosis in BHV-1-infected cells, and prolonged cell viability benefits BHV-1 replication.",2012 Sep 17,"['Xu, Xingang', 'Zhang, Kuan', 'Huang, Yong', 'Ding, Li', 'Chen, Guangda', 'Zhang, Honglei', 'Tong, Dewen']",Virol J,,,True
1a485fe46f5c18e940782aa60bb756d6ae2a6c0b,PMC,"Influenza Surveillance Among Children With Pneumonia Admitted to a District Hospital in Coastal Kenya, 2007–2010",http://dx.doi.org/10.1093/infdis/jis536,PMC3502370,23169974,CC BY,"Background. Influenza data gaps in sub-Saharan Africa include incidence, case fatality, seasonal patterns, and associations with prevalent disorders. Methods. Nasopharyngeal samples from children aged <12 years who were admitted to Kilifi District Hospital during 2007–2010 with severe or very severe pneumonia and resided in the local demographic surveillance system were screened for influenza A, B, and C viruses by molecular methods. Outpatient children provided comparative data. Results. Of 2002 admissions, influenza A virus infection was diagnosed in 3.5% (71), influenza B virus infection, in 0.9% (19); and influenza C virus infection, in 0.8% (11 of 1404 tested). Four patients with influenza died. Among outpatients, 13 of 331 (3.9%) with acute respiratory infection and 1 of 196 without acute respiratory infection were influenza positive. The annual incidence of severe or very severe pneumonia, of influenza (any type), and of influenza A, was 1321, 60, and 43 cases per 100 000 <5 years of age, respectively. Peak occurrence was in quarters 3–4 each year, and approximately 50% of cases involved infants: temporal association with bacteremia was absent. Hypoxia was more frequent among pneumonia cases involving influenza (odds ratio, 1.78; 95% confidence interval, 1.04–1.96). Influenza A virus subtypes were seasonal H3N2 (57%), seasonal H1N1 (12%), and 2009 pandemic H1N1 (7%). Conclusions. The burden of influenza was small during 2007–2010 in this pediatric hospital in Kenya. Influenza A virus subtype H3N2 predominated, and 2009 pandemic influenza A virus subtype H1N1 had little impact.",2012 Dec 15,"['Onyango, Clayton O.', 'Njeru, Regina', 'Kazungu, Sidi', 'Achilla, Rachel', 'Bulimo, Wallace', 'Welch, Stephen R.', 'Cane, Patricia A.', 'Gunson, Rory N.', 'Hammitt, Laura L.', 'Scott, J. Anthony G.', 'Berkley, James A.', 'Nokes, D. James']",J Infect Dis,,,True
abb624287a5b93c29ec470b38dd4d03b21c8fc34,PMC,Complete genome sequence of an astrovirus identified in a domestic rabbit (Oryctolagus cuniculus) with gastroenteritis,http://dx.doi.org/10.1186/1743-422X-9-216,PMC3502403,22998755,CC BY,"A colony of domestic rabbits in Tennessee, USA, experienced a high-mortality (~90%) outbreak of enterocolitis. The clinical characteristics were one to six days of lethargy, bloating, and diarrhea, followed by death. Heavy intestinal coccidial load was a consistent finding as was mucoid enteropathy with cecal impaction. Preliminary analysis by electron microscopy revealed the presence of virus-like particles in the stool of one of the affected rabbits. Analysis using the Virochip, a viral detection microarray, suggested the presence of an astrovirus, and follow-up PCR and sequence determination revealed a previously uncharacterized member of that family. Metagenomic sequencing enabled the recovery of the complete viral genome, which contains the characteristic attributes of astrovirus genomes. Attempts to propagate the virus in tissue culture have yet to succeed. Although astroviruses cause gastroenteric disease in other mammals, the pathogenicity of this virus and the relationship to this outbreak remains to be determined. This study therefore defines a viral species and a potential rabbit pathogen.",2012 Sep 22,"['Stenglein, Mark D', 'Velazquez, Eric', 'Greenacre, Cheryl', 'Wilkes, Rebecca P', 'Ruby, J Graham', 'Lankton, Julia S', 'Ganem, Donald', 'Kennedy, Melissa A', 'DeRisi, Joseph L']",Virol J,,,True
1f28ddf08dc9bb5b9b4c291f15d3d42ecdf9cde4,PMC,Bioinformatics and evolutionary insight on the spike glycoprotein gene of QX-like and Massachusetts strains of infectious bronchitis virus,http://dx.doi.org/10.1186/1743-422X-9-211,PMC3502414,22992336,CC BY,"BACKGROUND: Infectious bronchitis virus (IBV) is a Gammacoronavirus of the family Coronaviridae and is a causative agent of an economically important disease in poultry. The spike glycoprotein of IBV is essential for host cell attachment, neutralization, and is involved in the induction of protective immunity. Previously obtained sequence data of the spike gene of IBV QX-like and Massachusetts strains were subjected to bioinformatics analysis. FINDINGS: On analysis of potential phosphorylation sites, the Ser542 and Ser563 sites were not present in Massachusetts strains, while QX-like isolates did not have the Ser534 site. Massachusetts and QX-like strains showed different cleavage site motifs. The N-glycosylation sites ASN-XAA-SER/THR-55, 147, 200 and 545 were additionally present in QX-like strains. The leucine-rich repeat regions in Massachusetts strains consisted of stretches of 63 to 69 amino acids, while in the QX-like strains they contained 59 amino acids in length. An additional palmitoylation site was observed in CK/SWE/082066/2010 a QX-like strain. Primary structure data showed difference in the physical properties and hydrophobic nature of both genotypes. The comparison of secondary structures revealed no new structural domains in the genotypic variants. The phylogenetic analyses based on avian and mammalian coronaviruses showed the analysed IBV as closely related to turkey coronaviruses and distantly related to thrush and munia coronaviruses. CONCLUSION: The study demonstrated that spike glycoprotein of the Massachusetts and the QX-like variants of IBV are molecularly distinct and that this may reflect in differences in the behavior of these viruses in vivo.",2012 Sep 19,"['Abro, Shahid Hussain', 'Ullman, Karin', 'Belák, Sándor', 'Baule, Claudia']",Virol J,,,True
b2b90b3519bdcdd02d17595b01c3bb30cb8be63a,PMC,Comparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines,http://dx.doi.org/10.1186/1471-2172-13-54,PMC3503649,23013063,CC BY,"BACKGROUND: Despite the development of various systems to generate live recombinant Salmonella Typhimurium vaccine strains, little work has been performed to systematically evaluate and compare their relative immunogenicity. Such information would provide invaluable guidance for the future rational design of live recombinant Salmonella oral vaccines. RESULT: To compare vaccine strains encoded with different antigen delivery and expression strategies, a series of recombinant Salmonella Typhimurium strains were constructed that expressed either the enhanced green fluorescent protein (EGFP) or a fragment of the hemagglutinin (HA) protein from the H5N1 influenza virus, as model antigens. The antigens were expressed from the chromosome, from high or low-copy plasmids, or encoded on a eukaryotic expression plasmid. Antigens were targeted for expression in either the cytoplasm or the outer membrane. Combinations of strategies were employed to evaluate the efficacy of combined delivery/expression approaches. After investigating in vitro and in vivo antigen expression, growth and infection abilities; the immunogenicity of the constructed recombinant Salmonella strains was evaluated in mice. Using the soluble model antigen EGFP, our results indicated that vaccine strains with high and stable antigen expression exhibited high B cell responses, whilst eukaryotic expression or colonization with good construct stability was critical for T cell responses. For the insoluble model antigen HA, an outer membrane expression strategy induced better B cell and T cell responses than a cytoplasmic strategy. Most notably, the combination of two different expression strategies did not increase the immune response elicited. CONCLUSION: Through systematically evaluating and comparing the immunogenicity of the constructed recombinant Salmonella strains in mice, we identified their respective advantages and deleterious or synergistic effects. Different construction strategies were optimally-required for soluble versus insoluble forms of the protein antigens. If an antigen, such as EGFP, is soluble and expressed at high levels, a low-copy plasmid-cytoplasmic expression strategy is recommended; since it provokes the highest B cell responses and also induces good T cell responses. If a T cell response is preferred, a eukaryotic expression plasmid or a chromosome-based, cytoplasmic-expression strategy is more effective. For insoluble antigens such as HA, an outer membrane expression strategy is recommended.",2012 Sep 26,"['Zheng, Song-yue', 'Yu, Bin', 'Zhang, Ke', 'Chen, Min', 'Hua, Yan-Hong', 'Yuan, Shuofeng', 'Watt, Rory M', 'Zheng, Bo-Jian', 'Yuen, Kwok-Yung', 'Huang, Jian-Dong']",BMC Immunol,,,True
04c80346278c76be38e11fba9ee1a0fccc13c57f,PMC,Candidiasis and other oral mucosal lesions during and after interferon therapy for HCV-related chronic liver diseases,http://dx.doi.org/10.1186/1471-230X-12-155,PMC3503792,23122361,CC BY,"BACKGROUND: Oral lichen planus (OLP) is seen frequently in patients with hepatitis C virus (HCV) infection. The aim of this study was to evaluate the occurrence of oral candidiasis, other mucosal lesions, and xerostomia during interferon (IFN) therapy for HCV infection. METHODS: Of 124 patients with HCV-infected liver diseases treated with IFN therapy in our hospital, 14 (mean age 56.00 ± 12.94 years) who attended to receive administration of IFN once a week were identified and examined for Candida infection and other oral lesions and for the measurement of salivary flow. Serological assays also were carried out. RESULTS: Cultures of Candida from the tongue surfaces were positive in 7 (50.0%) of the 14 patients with HCV infection at least once during IFN therapy. C. albicans was the most common species isolated. The incidence of Candida during treatment with IFN did not increase above that before treatment. Additional oral mucosal lesions were observed in 50.0% (7/14) of patients: OLP in three (21.4%), angular cheilitis in three (21.4%) and recurrent aphthous stomatitis in one (7.1%). OLP occurred in one patient before treatment with IFN, in one during treatment and in one at the end of treatment. 85.7% of the oral lesions were treated with topical steroids. We compared the characteristics of the 7 patients in whom Candida was detected at least once during IFN therapy (group 1) and the 7 patients in whom Candida was not detected during IFN therapy (group 2). The prevalence of oral mucosal lesions (P=0.0075) and incidence of external use of steroids (P=0.0308) in group 1 were significantly higher than in group 2. The average body weight of group 1 decreased significantly compared to group 2 (P=0.0088). Salivary flow decreased in all subjects throughout the course of IFN treatment and returned at 6(th) months after the end of treatment. In group 1, the level of albumin at the beginning of the 6(th) month of IFN administration was lower than in group 2 (P=0.0550). According to multivariate analysis, one factor, the presence of oral mucosal lesions, was associated with the detection of Candida. The adjusted odds ratio for the factor was 36.00 (95% confidence interval 2.68-1485.94). CONCLUSION: We should pay more attention to oral candidiasis as well as other oral mucosal lesions, in patients with weight loss during IFN treatment.",2012 Nov 2,"['Nagao, Yumiko', 'Hashimoto, Kouji', 'Sata, Michio']",BMC Gastroenterol,,,True
697b9d764f13648fa38faa8d93fefde6049d6517,PMC,Human Monoclonal Antibodies against Highly Conserved HR1 and HR2 Domains of the SARS-CoV Spike Protein Are More Broadly Neutralizing,http://dx.doi.org/10.1371/journal.pone.0050366,PMC3503966,23185609,CC BY,"Immune sera from convalescent patients have been shown to be effective in the treatment of patients infected with Severe Acute Respiratory Syndrome Virus (SARS-CoV) making passive immune therapy with human monoclonal antibodies an attractive treatment strategy for SARS. Previously, using Xenomouse (Amgen British Columbia Inc), we produced a panel of neutralizing Human monoclonal antibodies (HmAbs) that could specifically bind to the ectodomain of the SARS-CoV spike (S) glycoprotein. Some of the HmAbs were S1 domain specific, while some were not. In this study, we describe non-S1 binding neutralizing HmAbs that can specifically bind to the conserved S2 domain of the S protein. However, unlike the S1 specific HmAbs, the S2 specific HmAbs can neutralize pseudotyped viruses expressing different S proteins containing receptor binding domain sequences of various clinical isolates. These data indicate that HmAbs which bind to conserved regions of the S protein are more suitable for conferring protection against a wide range of SARS-CoV variants and have implications for generating therapeutic antibodies or subunit vaccines against other enveloped viruses.",2012 Nov 21,"['Elshabrawy, Hatem A.', 'Coughlin, Melissa M.', 'Baker, Susan C.', 'Prabhakar, Bellur S.']",PLoS One,,,True
0cc12d028d0f63383a4243bb73d76f70ae229daa,PMC,Identification of a Conserved B-cell Epitope on Reticuloendotheliosis Virus Envelope Protein by Screening a Phage-displayed Random Peptide Library,http://dx.doi.org/10.1371/journal.pone.0049842,PMC3504085,23185456,CC BY,"BACKGROUND: The gp90 protein of avian reticuloendotheliosis-associated virus (REV-A) is an important envelope glycoprotein, which is responsible for inducing protective antibody immune responses in animals. B-cell epitopes on the gp90 protein of REV have not been well studied and reported. METHODS AND RESULTS: This study describes the identification of a linear B-cell epitope on the gp90 protein by screening a phage-displayed 12-mer random peptide library with the neutralizing monoclonal antibody (mAb) A9E8 directed against the gp90. The mAb A9E8 recognized phages displaying peptides with the consensus motif SVQYHPL. Amino acid sequence of the motif exactly matched (213)SVQYHPL(219) of the gp90. Further identification of the displayed B cell epitope was conducted using a set of truncated peptides expressed as GST fusion proteins and the Western blot results indicated that (213)SVQYHPL(219) was the minimal determinant of the linear B cell epitope recognized by the mAb A9E8. Moreover, an eight amino acid peptide SVQYHPLA was proven to be the minimal unit of the epitope with the maximal binding activity to mAb A9E8. The REV-A-positive chicken serum reacted with the minimal linear epitopes in Western blot, revealing the importance of the eight amino acids of the epitope in antibody-epitope binding activity. Furthermore, we found that the epitope is a common motif shared among REV-A and other members of REV group. CONCLUSIONS AND SIGNIFICANCE: We identified (213)SVQYHPL(219) as a gp90-specific linear B-cell epitope recognized by the neutralizing mAb A9E8. The results in this study may have potential applications in development of diagnostic techniques and epitope-based marker vaccines against REV-A and other viruses of the REV group.",2012 Nov 21,"['Xue, Mei', 'Shi, Xingming', 'Zhang, Jing', 'Zhao, Yan', 'Cui, Hongyu', 'Hu, Shunlei', 'Gao, Hongbo', 'Cui, Xianlan', 'Wang, Yun-Feng']",PLoS One,,,True
17752cd197628ca49a7b800528bdd68532e4a148,PMC,Ezrin Interacts with the SARS Coronavirus Spike Protein and Restrains Infection at the Entry Stage,http://dx.doi.org/10.1371/journal.pone.0049566,PMC3504146,23185364,CC BY,"BACKGROUND: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. METHODOLOGY/PRINCIPAL FINDINGS: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S-pseudotyped particles and potentiated S-dependent membrane fusion. CONCLUSIONS/SIGNIFICANCE: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.",2012 Nov 21,"['Millet, Jean Kaoru', 'Kien, François', 'Cheung, Chung-Yan', 'Siu, Yu-Lam', 'Chan, Wing-Lim', 'Li, Huiying', 'Leung, Hiu-Lan', 'Jaume, Martial', 'Bruzzone, Roberto', 'Malik Peiris, Joseph S.', 'Altmeyer, Ralf Marius', 'Nal, Béatrice']",PLoS One,,,True
6bc785e1a4016681657922ea713cb52b1c30e655,PMC,Lower Respiratory Tract Infection in a Renal Transplant Recipient: Do not Forget Metapneumovirus,http://dx.doi.org/10.1155/2012/353871,PMC3505633,23213611,CC BY,"Human metapneumovirus (hMPV) is emerging as a cause of a severe respiratory tract infection in immunocompromised patients. hMPV pneumonia has only been seldom reported in nonpulmonary solid organ transplanted patients, such as renal transplant recipients. We report here a case of a 39-year-old patient presenting with fever, cough, and interstitial opacities on CT scan diagnosed as a nonsevere hMPV pneumonia 11 years after a renal transplantation. Infection resolved spontaneously. Differential diagnosis with Pneumocystis pneumonia was discussed. We review the medical literature and discuss clinical presentation and detection methods that can be proposed in solid organ transplant recipients.",2012 Nov 14,"['Noel, N.', 'Rammaert, B.', 'Zuber, J.', 'Sayre, N.', 'Mamzer-Bruneel, M. F.', 'Leruez-Ville, M.', 'Mascard, L.', 'Lecuit, M.', 'Lortholary, O.']",Case Rep Transplant,,,True
05ce1f7ae3a2051067e57e5e52f9cdad0e26a187,PMC,The ORF2 glycoprotein of hepatitis E virus inhibits cellular NF-κB activity by blocking ubiquitination mediated proteasomal degradation of IκBα in human hepatoma cells,http://dx.doi.org/10.1186/1471-2091-13-7,PMC3506457,22590978,CC BY,"BACKGROUND: Nuclear factor kappa B (NF-κB) is a key transcription factor that plays a crucial role in host survival during infection by pathogens. Therefore, it has been a priority of many pathogens to manipulate the cellular NF-κB activity in order to create a favorable environment for their survival inside the host. RESULTS: We observed that heterologous expression of the open reading frame 2 (ORF2) protein in human hepatoma cells led to stabilization of the cellular I kappa B alpha (IκBα) pool, with a concomitant reduction in the nuclear localization of the p65 subunit of NF-κB and inhibition of NF-κB activity. Although basal or TPA induced phosphorylation of IκBα was not altered, its ubiquitination was markedly reduced in ORF2 expressing cells. Further analysis revealed that ORF2 protein could directly associate with the F-box protein, beta transducin repeat containing protein (βTRCP) and ORF2 over expression resulted in reduced association of IκBα with the SKP1 and CUL1 components of the SCF(βTRCP) complex. Chromatin immunoprecipitation (ChIP) assay of the proximal promoter regions of MHC-I heavy chain and IL-8 genes using p65 antibody and LPS stimulated ORF2 expressing cell extract revealed decreased association of p65 with the above regions, indicating that ORF2 inhibited p65 binding at endogenous promoters. CONCLUSIONS: In this report we suggest a mechanism by which ORF2 protein of HEV may inhibit host cell NF-κB activity during the course of a viral infection.",2012 May 16,"['Varshney, Bhavna', 'Lal, Sunil K']",BMC Biochem,,,True
434bd9335384207d750282844ad8ceb545e50462,PMC,Performance of LBSap Vaccine after Intradermal Challenge with L. infantum and Saliva of Lu. longipalpis: Immunogenicity and Parasitological Evaluation,http://dx.doi.org/10.1371/journal.pone.0049780,PMC3506642,23189161,CC BY,"In the last decade, the search for new vaccines against canine visceral leishmaniasis has intensified. However, the pattern related to immune protection during long periods after experimental infection in vaccine trials is still not fully understood. Herein, we investigated the immunogenicity and parasitological levels after intradermal challenge with Leishmania infantum plus salivary gland extract in dogs immunized with a vaccine composed of L. braziliensis antigens plus saponin as an adjuvant (LBSap vaccine). The LBSap vaccine elicited higher levels of total anti-Leishmania IgG as well as both IgG1 and IgG2. Furthermore, dogs vaccinated had increased levels of lymphocytes, particularly circulating B cells (CD21(+)) and both CD4(+) and CD8(+) T lymphocytes. LBSap also elicited an intense in vitro cell proliferation associated with higher levels of CD4(+) T lymphocytes specific for vaccine soluble antigen and soluble lysate of L. infantum antigen even 885 days after experimental challenge. Furthermore, LBSap vaccinated dogs presented high IFN-γ and low IL-10 and TGF-β1 expression in spleen with significant reduction of parasite load in this tissue. Overall, our results validate the potential of LBSap vaccine to protect against L. infantum experimental infection and strongly support further evaluation of efficiency of LBSap against CVL in natural infection conditions.",2012 Nov 26,"['Roatt, Bruno Mendes', 'Aguiar-Soares, Rodrigo Dian de Oliveira', 'Vitoriano-Souza, Juliana', 'Coura-Vital, Wendel', 'Braga, Samuel Leôncio', 'Corrêa-Oliveira, Rodrigo', 'Martins-Filho, Olindo Assis', 'Teixeira-Carvalho, Andréa', 'de Lana, Marta', 'Gontijo, Nelder Figueiredo', 'Marques, Marcos José', 'Giunchetti, Rodolfo Cordeiro', 'Reis, Alexandre Barbosa']",PLoS One,,,True
e53306862eb2cab646ba36a1e685fdb5a392da42,PMC,A new look at an old virus: patterns of mutation accumulation in the human H1N1 influenza virus since 1918,http://dx.doi.org/10.1186/1742-4682-9-42,PMC3507676,23062055,CC BY,"BACKGROUND: The H1N1 influenza A virus has been circulating in the human population for over 95 years, first manifesting itself in the pandemic of 1917–1918. Initial mortality was extremely high, but dropped exponentially over time. Influenza viruses have high mutation rates, and H1N1 has undergone significant genetic changes since 1918. The exact nature of H1N1 mutation accumulation over time has not been fully explored. METHODS: We have made a comprehensive historical analysis of mutational changes within H1N1 by examining over 4100 fully-sequenced H1N1 genomes. This has allowed us to examine the genetic changes arising within H1N1 from 1918 to the present. RESULTS: We document multiple extinction events, including the previously known extinction of the human H1N1 lineage in the 1950s, and an apparent second extinction of the human H1N1 lineage in 2009. These extinctions appear to be due to a continuous accumulation of mutations. At the time of its disappearance in 2009, the human H1N1 lineage had accumulated over 1400 point mutations (more than 10% of the genome), including approximately 330 non-synonymous changes (7.4% of all codons). The accumulation of both point mutations and non-synonymous amino acid changes occurred at constant rates (μ = 14.4 and 2.4 new mutations/year, respectively), and mutations accumulated uniformly across the entire influenza genome. We observed a continuous erosion over time of codon-specificity in H1N1, including a shift away from host (human, swine, and bird [duck]) codon preference patterns. CONCLUSIONS: While there have been numerous adaptations within the H1N1 genome, most of the genetic changes we document here appear to be non-adaptive, and much of the change appears to be degenerative. We suggest H1N1 has been undergoing natural genetic attenuation, and that significant attenuation may even occur during a single pandemic. This process may play a role in natural pandemic cessation and has apparently contributed to the exponential decline in mortality rates over time, as seen in all major human influenza strains. These findings may be relevant to the development of strategies for managing influenza pandemics and strain evolution.",2012 Oct 12,"['Carter, Robert W', 'Sanford, John C']",Theor Biol Med Model,,,True
4ed134293562340d043a5e0b6f5d822df7cf7079,PMC,"Functional repertoire, molecular pathways and diseases associated with 3D domain swapping in the human proteome",http://dx.doi.org/10.1186/2043-9113-2-8,PMC3508620,22472218,CC BY,"BACKGROUND: 3D domain swapping is a novel structural phenomenon observed in diverse set of protein structures in oligomeric conformations. A distinct structural feature, where structural segments in a protein dimer or higher oligomer were shared between two or more chains of a protein structure, characterizes 3D domain swapping. 3D domain swapping was observed as a key mediator of numerous functional mechanisms and play pathogenic role in various diseases including conformational diseases like amyloidosis, Alzheimer's disease, Parkinson's disease and prion diseases. We report the first study with a focus on identifying functional classes, pathways and diseases mediated by 3D domain swapping in the human proteome. METHODS: We used a panel of four enrichment tools with two different ontologies and two annotations database to derive biological and clinical relevant information associated with 3D domain swapping. Protein domain enrichment analysis followed by Gene Ontology (GO) term enrichment analysis revealed the functional repertoire of proteins involved in swapping. Pathway analysis using KEGG annotations revealed diverse pathway associations of human proteins involved in 3D domain swapping. Disease Ontology was used to find statistically significant associations with proteins in swapped conformation and various disease categories (P-value < 0.05). RESULTS: We report meta-analysis results of a literature-curated dataset of human gene products involved in 3D domain swapping and discuss new insights about the functional repertoire, pathway associations and disease implications of proteins involved in 3D domain swapping. CONCLUSIONS: Our integrated bioinformatics pipeline comprising of four different enrichment tools, two ontologies and two annotations revealed new insights into the functional and disease correlations with 3D domain swapping. GO term enrichment were used to infer terms associated with three different GO categories. Protein domain enrichment was used to identify conserved domains enriched in swapped proteins. Pathway enrichment analysis using KEGG annotations revealed that proteins with swapped conformations are present in all six classes of KEGG BRITE hierarchy and significantly enriched KEGG pathways were observed in five classes. Five major classes of disease were found to be associated with 3D domain swapping using functional disease ontology based enrichment analysis. Five classes of human diseases: cancer, diseases of the respiratory or pulmonary system, degenerative diseases of the central nervous system, vascular disease and encephalitis were found to be significant. In conclusion, our study shows that bioinformatics based analytical approaches using curated data can enhance the understanding of functional and disease implications of 3D domain swapping.",2012 Apr 3,"['Shameer, Khader', 'Sowdhamini, Ramanathan']",J Clin Bioinforma,,,True
4d4de01a6f9ad02ac0939d54713c209153fa66df,PMC,Development and evaluation of an immunochromatographic strip for rapid detection of porcine hemagglutinating encephalomyelitis virus,http://dx.doi.org/10.1186/1743-422X-9-172,PMC3508965,22920192,CC BY,"BACKGROUND: The incidence of PHE among pigs in many countries is on the rise, and it has caused great economic losses to the pig industry. Therefore, the development of a sensitive, specific, and easily-performed assay is crucial for the rapid detection and surveillance of PHE-CoV infection and transmission. RESULTS: An immunochromatographic strip was developed for the detection of PHE-CoV. The colloidal gold-labeled MAb 4D4 was used as the detection reagent, and the MAb 1E2 and goat anti-mouse IgG coated the strip's test and control lines, respectively. The immunochromatographic strip was capable of specifically detecting PHE-CoV with a HA unit of 2 within 10 min. Storage of the strips at room temperature for 6 months or at 4°C for 12 months did not change their sensitivity or specificity. Using RT-PCR as a reference test, the relative specificity and sensitivity of the immunochromatographic strip were determined to be 100% and 97.78%, respectively. There was an excellent agreement between the results obtained by RT-PCR and the immunochromatographic strips (kappa = 0.976). Additionally, there was a strong agreement between the sandwich enzyme-linked immunosorbent assay (ELISA) and immunochromatographic strips (Kappa = 0.976). When the immunochromatographic strips were used for diagnosing PHE-CoV infection in the Jilin Province, the PHE-CoV-positive rate ranged from 61.54% in the Jilin district to 17.95% in the Songyuan district. CONCLUSIONS: Based on its high specificity, sensitivity, and stability, the immunochromatographic strip would be suitable for on-site detection of PHE-CoV for surveillance and epidemiological purposes.",2012 Aug 24,"['Chen, Keyan', 'Zhao, Kui', 'Song, Deguang', 'He, Wenqi', 'Gao, Wei', 'Zhao, Chuanbo', 'Wang, Chengli', 'Gao, Feng']",Virol J,,,True
8a8463146cf8f61c2d62df2adaa251adbe2f9dc1,PMC,"Burden of influenza, healthcare seeking behaviour and hygiene measures during the A(H1N1)2009 pandemic in France: a population based study",http://dx.doi.org/10.1186/1471-2458-12-947,PMC3508974,23127166,CC BY,"BACKGROUND: Influenza surveillance systems do not allow the identification of the true burden of illness caused by influenza in the community because they are restricted to consulting cases. A study was conducted to estimate the incidence and the burden of self-defined influenza, and to describe healthcare seeking behavior for self-defined influenza during the A(H1N1)2009 pandemic in the French population. METHODS: We conducted a random-based retrospective cross-sectional telephone survey between May 2009 and April 2010 among a random sample of the French population. RESULTS: For the 10 076 people included, 107 episodes of self-defined influenza were reported. The annual incidence of self-defined influenza was estimated at 13 942 cases per 100 000 inhabitants (CI95% 10 947 – 16 961), 62.1% (CI95% 50.5 – 72.5) of cases consulted a physician and 11.3% (CI95% 5.5 - 21.7) used a face mask. Following recommendations, 37.5% (CI95% 35.5 – 39.5) of people in the survey reported washing their hands more often during the pandemic season, and there was a positive association with being vaccinated against A(H1N1)2009 influenza, being a women, being a child (< 15 years) or living in a big city (≥ 100 000 inhabitants). CONCLUSIONS: Self-defined influenza causes a significant burden of illness in the French population and is a frequent cause for consultation. These results allow a more accurate interpretation of influenza surveillance data and an opportunity to adapt future health education messages.",2012 Nov 5,"['Van Cauteren, Dieter', 'Vaux, Sophie', 'de Valk, Henriette', 'Le Strat, Yann', 'Vaillant, Véronique', 'Lévy-Bruhl, Daniel']",BMC Public Health,,,True
df51bfb59565119816648b8f02f5a4f25ee4a76c,PMC,Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator,http://dx.doi.org/10.1186/1471-2458-12-870,PMC3509032,23061807,CC BY,"BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.",2012 Oct 12,"['Stein, Mart Lambertus', 'Rudge, James W', 'Coker, Richard', 'van der Weijden, Charlie', 'Krumkamp, Ralf', 'Hanvoravongchai, Piya', 'Chavez, Irwin', 'Putthasri, Weerasak', 'Phommasack, Bounlay', 'Adisasmito, Wiku', 'Touch, Sok', 'Sat, Le Minh', 'Hsu, Yu-Chen', 'Kretzschmar, Mirjam', 'Timen, Aura']",BMC Public Health,,,True
98ebefa9ea63cabfcfac33fb259adf77a19428af,PMC,Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator,http://dx.doi.org/10.1186/1471-2458-12-870,PMC3509032,23061807,CC BY,"BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.",2012 Oct 12,"['Stein, Mart Lambertus', 'Rudge, James W', 'Coker, Richard', 'van der Weijden, Charlie', 'Krumkamp, Ralf', 'Hanvoravongchai, Piya', 'Chavez, Irwin', 'Putthasri, Weerasak', 'Phommasack, Bounlay', 'Adisasmito, Wiku', 'Touch, Sok', 'Sat, Le Minh', 'Hsu, Yu-Chen', 'Kretzschmar, Mirjam', 'Timen, Aura']",BMC Public Health,,,True
d8714feba6d9a8670db5d8e4d998a3de95d16a3c,PMC,Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator,http://dx.doi.org/10.1186/1471-2458-12-870,PMC3509032,23061807,CC BY,"BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.",2012 Oct 12,"['Stein, Mart Lambertus', 'Rudge, James W', 'Coker, Richard', 'van der Weijden, Charlie', 'Krumkamp, Ralf', 'Hanvoravongchai, Piya', 'Chavez, Irwin', 'Putthasri, Weerasak', 'Phommasack, Bounlay', 'Adisasmito, Wiku', 'Touch, Sok', 'Sat, Le Minh', 'Hsu, Yu-Chen', 'Kretzschmar, Mirjam', 'Timen, Aura']",BMC Public Health,,,True
dd40b192bbddb785dd3f6e42e45853cd4b14cdca,PMC,Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator,http://dx.doi.org/10.1186/1471-2458-12-870,PMC3509032,23061807,CC BY,"BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.",2012 Oct 12,"['Stein, Mart Lambertus', 'Rudge, James W', 'Coker, Richard', 'van der Weijden, Charlie', 'Krumkamp, Ralf', 'Hanvoravongchai, Piya', 'Chavez, Irwin', 'Putthasri, Weerasak', 'Phommasack, Bounlay', 'Adisasmito, Wiku', 'Touch, Sok', 'Sat, Le Minh', 'Hsu, Yu-Chen', 'Kretzschmar, Mirjam', 'Timen, Aura']",BMC Public Health,,,True
323975b3348556eb9cf84e82ffcc51de563d1379,PMC,Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator,http://dx.doi.org/10.1186/1471-2458-12-870,PMC3509032,23061807,CC BY,"BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.",2012 Oct 12,"['Stein, Mart Lambertus', 'Rudge, James W', 'Coker, Richard', 'van der Weijden, Charlie', 'Krumkamp, Ralf', 'Hanvoravongchai, Piya', 'Chavez, Irwin', 'Putthasri, Weerasak', 'Phommasack, Bounlay', 'Adisasmito, Wiku', 'Touch, Sok', 'Sat, Le Minh', 'Hsu, Yu-Chen', 'Kretzschmar, Mirjam', 'Timen, Aura']",BMC Public Health,,,False
48cc713567a278caa4b15e0528e1babe71efe44c,PMC,Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator,http://dx.doi.org/10.1186/1471-2458-12-870,PMC3509032,23061807,CC BY,"BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.",2012 Oct 12,"['Stein, Mart Lambertus', 'Rudge, James W', 'Coker, Richard', 'van der Weijden, Charlie', 'Krumkamp, Ralf', 'Hanvoravongchai, Piya', 'Chavez, Irwin', 'Putthasri, Weerasak', 'Phommasack, Bounlay', 'Adisasmito, Wiku', 'Touch, Sok', 'Sat, Le Minh', 'Hsu, Yu-Chen', 'Kretzschmar, Mirjam', 'Timen, Aura']",BMC Public Health,,,True
dfe39ec7e5950a8ca7d5e0d1a503176f0fc824c2,PMC,Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator,http://dx.doi.org/10.1186/1471-2458-12-870,PMC3509032,23061807,CC BY,"BACKGROUND: Health care planning for pandemic influenza is a challenging task which requires predictive models by which the impact of different response strategies can be evaluated. However, current preparedness plans and simulations exercises, as well as freely available simulation models previously made for policy makers, do not explicitly address the availability of health care resources or determine the impact of shortages on public health. Nevertheless, the feasibility of health systems to implement response measures or interventions described in plans and trained in exercises depends on the available resource capacity. As part of the AsiaFluCap project, we developed a comprehensive and flexible resource modelling tool to support public health officials in understanding and preparing for surges in resource demand during future pandemics. RESULTS: The AsiaFluCap Simulator is a combination of a resource model containing 28 health care resources and an epidemiological model. The tool was built in MS Excel© and contains a user-friendly interface which allows users to select mild or severe pandemic scenarios, change resource parameters and run simulations for one or multiple regions. Besides epidemiological estimations, the simulator provides indications on resource gaps or surpluses, and the impact of shortages on public health for each selected region. It allows for a comparative analysis of the effects of resource availability and consequences of different strategies of resource use, which can provide guidance on resource prioritising and/or mobilisation. Simulation results are displayed in various tables and graphs, and can also be easily exported to GIS software to create maps for geographical analysis of the distribution of resources. CONCLUSIONS: The AsiaFluCap Simulator is freely available software (http://www.cdprg.org) which can be used by policy makers, policy advisors, donors and other stakeholders involved in preparedness for providing evidence based and illustrative information on health care resource capacities during future pandemics. The tool can inform both preparedness plans and simulation exercises and can help increase the general understanding of dynamics in resource capacities during a pandemic. The combination of a mathematical model with multiple resources and the linkage to GIS for creating maps makes the tool unique compared to other available software.",2012 Oct 12,"['Stein, Mart Lambertus', 'Rudge, James W', 'Coker, Richard', 'van der Weijden, Charlie', 'Krumkamp, Ralf', 'Hanvoravongchai, Piya', 'Chavez, Irwin', 'Putthasri, Weerasak', 'Phommasack, Bounlay', 'Adisasmito, Wiku', 'Touch, Sok', 'Sat, Le Minh', 'Hsu, Yu-Chen', 'Kretzschmar, Mirjam', 'Timen, Aura']",BMC Public Health,,,False
699369c8d371b09fca7aeb53e54b3b569e1653d0,PMC,What was the primary mode of smallpox transmission? Implications for biodefense,http://dx.doi.org/10.3389/fcimb.2012.00150,PMC3509329,23226686,CC BY,"The mode of infection transmission has profound implications for effective containment by public health interventions. The mode of smallpox transmission was never conclusively established. Although, “respiratory droplet” transmission was generally regarded as the primary mode of transmission, the relative importance of large ballistic droplets and fine particle aerosols that remain suspended in air for more than a few seconds was never resolved. This review examines evidence from the history of variolation, data on mucosal infection collected in the last decades of smallpox transmission, aerosol measurements, animal models, reports of smallpox lung among healthcare workers, and the epidemiology of smallpox regarding the potential importance of fine particle aerosol mediated transmission. I introduce briefly the term anisotropic infection to describe the behavior of Variola major in which route of infection appears to have altered the severity of disease.",2012 Nov 29,"Milton, Donald K.",Front Cell Infect Microbiol,,,True
3c44fe859327f5e7b02cc27a10a228ae5288d65b,PMC,Comparative Genomics of Korean Infectious Bronchitis Viruses (IBVs) and an Animal Model to Evaluate Pathogenicity of IBVs to the Reproductive Organs,http://dx.doi.org/10.3390/v4112670,PMC3509667,23202499,CC BY,"The K-I and nephropathogenic K-II genotypes of infectious bronchitis virus (IBV) have been isolated since 1995 and 1990, respectively, in Korea and commercial inactivated oil-emulsion vaccines containing KM91 (K-II type) and Massachusetts 41 strains have been used in the field. To date, genomic analyses of Korean IBV strains and animal models to test the pathogenicity of Korean IBVs to the reproductive organs have been rare. In the present study, comparative genomics of SNU8067 (K-I type) and KM91 IBVs was performed, and an animal model to test the pathogenicity of SNU8067 was established and applied to vaccine efficacy test. The genome sizes of SNU8067 (27,708 nt) and KM91 (27,626 nt) were slightly different and the nucleotide and amino acid identities of the S1 (79%, 77%), 3a (65%, 52%), and 3b (81%, 72%) genes were lower than those of other genes (94%–97%, 92%–98%). A recombination analysis revealed that SNU8067 was a recombinant virus with a KM91-like backbone except S1, 3a, and 3b genes which might be from an unknown virus. An SNU8067 infection inhibited formation of hierarchal ovarian follicles (80%) and oviduct maturation (50%) in the control group, whereas 70% of vaccinated chickens were protected from lesions.",2012 Oct 30,"['Hong, Seung-Min', 'Kwon, Hyuk-Joon', 'Kim, Il-Hwan', 'Mo, Mei-Lan', 'Kim, Jae-Hong']",Viruses,,,True
59ac4eae51d6084c2346ebd27125a3b56e25d72e,PMC,Clinical Aspects of Feline Retroviruses: A Review,http://dx.doi.org/10.3390/v4112684,PMC3509668,23202500,CC BY,"Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia), and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less commonly diagnosed than in the previous 20 years; prevalence has been decreasing in most countries. However, FeLV importance may be underestimated as it has been shown that regressively infected cats (that are negative in routinely used FeLV tests) also can develop clinical signs. FIV can cause an acquired immunodeficiency syndrome that increases the risk of opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. This article provides a review of clinical syndromes in progressively and regressively FeLV-infected cats as well as in FIV-infected cats.",2012 Oct 31,"Hartmann, Katrin",Viruses,,,True
b0dcc756c7f2641a8319b96355ec871ba2922f90,PMC,"Use of an Innovative Web-Based Laboratory Surveillance Platform to Analyze Mixed Infections Between Human Metapneumovirus (hMPV) and Other Respiratory Viruses Circulating in Alberta (AB), Canada (2009–2012)",http://dx.doi.org/10.3390/v4112754,PMC3509671,23202503,CC BY,"We investigated the proportions of mono vs. mixed infections for human metapneumovirus (hMPV) as compared to adenovirus (ADV), four types of coronavirus (CRV), parainfluenza virus (PIV), RSV, and enterovirus/rhinovirus (ERV) in Alberta, Canada. Using the Data Integration for Alberta Laboratories (DIAL) platform, 26,226 respiratory specimens at ProvLab between 1 July 2009 and 30 June 2012 were selected and included in the study. Using the Respiratory Virus Panel these specimens tested positive for one or more respiratory virus and negative for influenza A and B. From our subset hMPV was the fourth most common virus (n=2,561) with 373 (15%) identified as mixed infection using DIAL. Mixed infection with hMPV was most commonly found in infants less than 6 months old and ERV was most commonly found in mixed infection with hMPV (230/373, 56%) across all age groups. The proportion of mixed-infection vs. mono-infection was highest for ADV (46%), followed by CRV 229E (32%), CRV HKU1 (31%), CRV NL63 (28%), CRV OC43 (23%), PIV (20%), RSV (17%), hMPV (15%) and ERV (13%). hMPV was significantly more likely to be identified in mono infection as compared with ADV, CRV, PIV, and RSV with the exception of ERV [p<0.05].",2012 Nov 5,"['Fathima, Sumana', 'Lee, Bonita E.', 'May-Hadford, Jennifer', 'Mukhi, Shamir', 'Drews, Steven J.']",Viruses,,,True
54447606d747c1bb9865d1b344bdd8ad0e200bf0,PMC,The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis,http://dx.doi.org/10.3390/v4112902,PMC3509677,23202509,CC BY,"A respiratory disease caused by a novel coronavirus, termed the severe acute respiratory syndrome coronavirus (SARS-CoV), was first reported in China in late 2002. The subsequent efficient human-to-human transmission of this virus eventually affected more than 30 countries worldwide, resulting in a mortality rate of ~10% of infected individuals. The spread of the virus was ultimately controlled by isolation of infected individuals and there has been no infections reported since April 2004. However, the natural reservoir of the virus was never identified and it is not known if this virus will re-emerge and, therefore, research on this virus continues. The SARS-CoV genome is about 30 kb in length and is predicted to contain 14 functional open reading frames (ORFs). The genome encodes for proteins that are homologous to known coronavirus proteins, such as the replicase proteins (ORFs 1a and 1b) and the four major structural proteins: nucleocapsid (N), spike (S), membrane (M) and envelope (E). SARS-CoV also encodes for eight unique proteins, called accessory proteins, with no known homologues. This review will summarize the current knowledge on SARS-CoV accessory proteins and will include: (i) expression and processing; (ii) the effects on cellular processes; and (iii) functional studies.",2012 Nov 7,"['McBride, Ruth', 'Fielding, Burtram C.']",Viruses,,,True
d171f82b892a2afafc2bc8a5458219dc04c8fd8d,PMC,Human Coronaviruses: Insights into Environmental Resistance and Its Influence on the Development of New Antiseptic Strategies,http://dx.doi.org/10.3390/v4113044,PMC3509683,23202515,CC BY,"The Coronaviridae family, an enveloped RNA virus family, and, more particularly, human coronaviruses (HCoV), were historically known to be responsible for a large portion of common colds and other upper respiratory tract infections. HCoV are now known to be involved in more serious respiratory diseases, i.e. bronchitis, bronchiolitis or pneumonia, especially in young children and neonates, elderly people and immunosuppressed patients. They have also been involved in nosocomial viral infections. In 2002–2003, the outbreak of severe acute respiratory syndrome (SARS), due to a newly discovered coronavirus, the SARS-associated coronavirus (SARS-CoV); led to a new awareness of the medical importance of the Coronaviridae family. This pathogen, responsible for an emerging disease in humans, with high risk of fatal outcome; underline the pressing need for new approaches to the management of the infection, and primarily to its prevention. Another interesting feature of coronaviruses is their potential environmental resistance, despite the accepted fragility of enveloped viruses. Indeed, several studies have described the ability of HCoVs (i.e. HCoV 229E, HCoV OC43 (also known as betacoronavirus 1), NL63, HKU1 or SARS-CoV) to survive in different environmental conditions (e.g. temperature and humidity), on different supports found in hospital settings such as aluminum, sterile sponges or latex surgical gloves or in biological fluids. Finally, taking into account the persisting lack of specific antiviral treatments (there is, in fact, no specific treatment available to fight coronaviruses infections), the Coronaviridae specificities (i.e. pathogenicity, potential environmental resistance) make them a challenging model for the development of efficient means of prevention, as an adapted antisepsis-disinfection, to prevent the environmental spread of such infective agents. This review will summarize current knowledge on the capacity of human coronaviruses to survive in the environment and the efficacy of well-known antiseptic-disinfectants against them, with particular focus on the development of new methodologies to evaluate the activity of new antiseptic-disinfectants on viruses.",2012 Nov 12,"['Geller, Chloé', 'Varbanov, Mihayl', 'Duval, Raphaël E.']",Viruses,,,True
9680a6922144725138edc920dbf6c3dc48e822b6,PMC,Virus Pathogen Database and Analysis Resource (ViPR): A Comprehensive Bioinformatics Database and Analysis Resource for the Coronavirus Research Community,http://dx.doi.org/10.3390/v4113209,PMC3509690,23202522,CC BY,"Several viruses within the Coronaviridae family have been categorized as either emerging or re-emerging human pathogens, with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) being the most well known. The NIAID-sponsored Virus Pathogen Database and Analysis Resource (ViPR, www.viprbrc.org) supports bioinformatics workflows for a broad range of human virus pathogens and other related viruses, including the entire Coronaviridae family. ViPR provides access to sequence records, gene and protein annotations, immune epitopes, 3D structures, host factor data, and other data types through an intuitive web-based search interface. Records returned from these queries can then be subjected to web-based analyses including: multiple sequence alignment, phylogenetic inference, sequence variation determination, BLAST comparison, and metadata-driven comparative genomics statistical analysis. Additional tools exist to display multiple sequence alignments, view phylogenetic trees, visualize 3D protein structures, transfer existing reference genome annotations to new genomes, and store or share results from any search or analysis within personal private ‘Workbench’ spaces for future access. All of the data and integrated analysis and visualization tools in ViPR are made available without charge as a service to the Coronaviridae research community to facilitate the research and development of diagnostics, prophylactics, vaccines and therapeutics against these human pathogens.",2012 Nov 19,"['Pickett, Brett E.', 'Greer, Douglas S.', 'Zhang, Yun', 'Stewart, Lucy', 'Zhou, Liwei', 'Sun, Guangyu', 'Gu, Zhiping', 'Kumar, Sanjeev', 'Zaremba, Sam', 'Larsen, Christopher N.', 'Jen, Wei', 'Klem, Edward B.', 'Scheuermann, Richard H.']",Viruses,,,True
8791721a89fa47907acb71d4fc4fdae9ab76156e,PMC,Virus Pathogen Database and Analysis Resource (ViPR): A Comprehensive Bioinformatics Database and Analysis Resource for the Coronavirus Research Community,http://dx.doi.org/10.3390/v4113209,PMC3509690,23202522,CC BY,"Several viruses within the Coronaviridae family have been categorized as either emerging or re-emerging human pathogens, with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) being the most well known. The NIAID-sponsored Virus Pathogen Database and Analysis Resource (ViPR, www.viprbrc.org) supports bioinformatics workflows for a broad range of human virus pathogens and other related viruses, including the entire Coronaviridae family. ViPR provides access to sequence records, gene and protein annotations, immune epitopes, 3D structures, host factor data, and other data types through an intuitive web-based search interface. Records returned from these queries can then be subjected to web-based analyses including: multiple sequence alignment, phylogenetic inference, sequence variation determination, BLAST comparison, and metadata-driven comparative genomics statistical analysis. Additional tools exist to display multiple sequence alignments, view phylogenetic trees, visualize 3D protein structures, transfer existing reference genome annotations to new genomes, and store or share results from any search or analysis within personal private ‘Workbench’ spaces for future access. All of the data and integrated analysis and visualization tools in ViPR are made available without charge as a service to the Coronaviridae research community to facilitate the research and development of diagnostics, prophylactics, vaccines and therapeutics against these human pathogens.",2012 Nov 19,"['Pickett, Brett E.', 'Greer, Douglas S.', 'Zhang, Yun', 'Stewart, Lucy', 'Zhou, Liwei', 'Sun, Guangyu', 'Gu, Zhiping', 'Kumar, Sanjeev', 'Zaremba, Sam', 'Larsen, Christopher N.', 'Jen, Wei', 'Klem, Edward B.', 'Scheuermann, Richard H.']",Viruses,,,False
3e18531b5a0a745c732d05de8eac8862a9b6a8e9,PMC,Biogenesis and Dynamics of the Coronavirus Replicative Structures,http://dx.doi.org/10.3390/v4113245,PMC3509692,23202524,CC BY,"Coronaviruses are positive-strand RNA viruses that are important infectious agents of both animals and humans. A common feature among positive-strand RNA viruses is their assembly of replication-transcription complexes in association with cytoplasmic membranes. Upon infection, coronaviruses extensively rearrange cellular membranes into organelle-like replicative structures that consist of double-membrane vesicles and convoluted membranes to which the nonstructural proteins involved in RNA synthesis localize. Double-stranded RNA, presumably functioning as replicative intermediate during viral RNA synthesis, has been detected at the double-membrane vesicle interior. Recent studies have provided new insights into the assembly and functioning of the coronavirus replicative structures. This review will summarize the current knowledge on the biogenesis of the replicative structures, the membrane anchoring of the replication-transcription complexes, and the location of viral RNA synthesis, with particular focus on the dynamics of the coronavirus replicative structures and individual replication-associated proteins.",2012 Nov 21,"['Hagemeijer, Marne C.', 'Rottier, Peter J.M.', 'de Haan, Cornelis A.M.']",Viruses,,,True
30a8e34179b5cc12c971eaa2b40015a446f10621,PMC,Chitinase Dependent Control of Protozoan Cyst Burden in the Brain,http://dx.doi.org/10.1371/journal.ppat.1002990,PMC3510238,23209401,CC0,"Chronic infections represent a continuous battle between the host's immune system and pathogen replication. Many protozoan parasites have evolved a cyst lifecycle stage that provides it with increased protection from environmental degradation as well as endogenous host mechanisms of attack. In the case of Toxoplasma gondii, these cysts are predominantly found in the immune protected brain making clearance of the parasite more difficult and resulting in a lifelong infection. Currently, little is known about the nature of the immune response stimulated by the presence of these cysts or how they are able to propagate. Here we establish a novel chitinase-dependent mechanism of cyst control in the infected brain. Despite a dominant Th1 immune response during Toxoplasma infection there exists a population of alternatively activated macrophages (AAMØ) in the infected CNS. These cells are capable of cyst lysis via the production of AMCase as revealed by live imaging, and this chitinase is necessary for protective immunity within the CNS. These data demonstrate chitinase activity in the brain in response to a protozoan pathogen and provide a novel mechanism to facilitate cyst clearance during chronic infections.",2012 Nov 29,"['Nance, J. Philip', 'Vannella, Kevin M.', 'Worth, Danielle', 'David, Clément', 'Carter, David', 'Noor, Shahani', 'Hubeau, Cedric', 'Fitz, Lori', 'Lane, Thomas E.', 'Wynn, Thomas A.', 'Wilson, Emma H.']",PLoS Pathog,,,True
80ce020acc7d023a1bc60a5f42c2afc937e3a200,PMC,Diagnostic value of respiratory virus detection in symptomatic children using real-time PCR,http://dx.doi.org/10.1186/1743-422X-9-276,PMC3511061,23164039,CC BY,"BACKGROUND: Acute respiratory tract infections are an important public health problem. Sensitive and rapid diagnostic techniques have been developed and are used in daily clinical practice. Here we evaluate the clinical relevance of detecting 20 common respiratory pathogens by molecular methods in a general pediatric clinic. METHODS: Nasopharynx samples of children < 18 years of age with respiratory symptoms referred to a general pediatric clinic were tested for the presence of 19 viruses and Mycoplasma pneumoniae, using real-time polymerase chain reaction. RESULTS: Of 177 patients included in this retrospective study, 73% were positive for at least one virus. Respiratory syncytial virus (36.6%) and human rhinovirus (24%) were most frequently detected. Patients in whom a respiratory virus or Mycoplasma pneumoniae was detected, were younger (6 versus 24 months; p < 0.001) and more often hospitalized (116 versus 34; p = 0.001) than patients in whom no respiratory pathogen was detected. Also they were more likely to present with feeding problems, dyspnea, rhinorrhea and wheezing (all p < 0.05) than patients without a respiratory pathogen. In the majority of cases, clinicians did not change their antibiotic management after detecting a viral respiratory pathogen. No difference in mean Ct value was found between patients with one respiratory pathogen and those with >1 respiratory pathogen (30.5 versus 31.2; p = 0.573). CONCLUSION: Routine testing of common respiratory pathogens could lead to a better understanding of their role in disease in children with respiratory symptoms.",2012 Nov 19,"['Huijskens, Elisabeth G', 'Biesmans, Renée C', 'Buiting, Anton G', 'Obihara, Charles C', 'Rossen, John W']",Virol J,,,True
2a7c951e191425fd9fa5ac108f07a1f02eb75872,PMC,The changing phenotype of microglia from homeostasis to disease,http://dx.doi.org/10.1186/2047-9158-1-9,PMC3514090,23210447,CC BY,"It has been nearly a century since the early description of microglia by Rio-Hortega; since then many more biological and pathological features of microglia have been recognized. Today, microglia are generally considered to be beneficial to homeostasis at the resting state through their abilities to survey the environment and phagocytose debris. However, when activated microglia assume diverse phenotypes ranging from fully inflamed, which involves the release of many pro-inflammatory cytokines, to alternatively activated, releasing anti-inflammatory cytokines or neurotrophins, the consequences to neurons can range from detrimental to supportive. Due to the different experimental sets and conditions, contradictory results have been obtained regarding the controversial question of whether microglia are “good” or “bad.” While it is well understood that the dual roles of activated microglia depend on specific situations, the underlying mechanisms have remained largely unclear, and the interpretation of certain findings related to diverse microglial phenotypes continues to be problematic. In this review we discuss the functions of microglia in neuronal survival and neurogenesis, the crosstalk between microglia and surrounding cells, and the potential factors that could influence the eventual manifestation of microglia.",2012 Apr 24,"['Luo, Xiao-Guang', 'Chen, Sheng-Di']",Transl Neurodegener,,,True
854e623d1f875e4605b2ffd3f72599d063a56cc0,PMC,Diversity of Salmonella spp. serovars isolated from the intestines of water buffalo calves with gastroenteritis,http://dx.doi.org/10.1186/1746-6148-8-201,PMC3514206,23098237,CC BY,"BACKGROUND: Salmonellosis in water buffalo (Bubalus bubalis) calves is a widespread disease characterized by severe gastrointestinal lesions, profuse diarrhea and severe dehydration, occasionally exhibiting a systemic course. Several Salmonella serovars seem to be able to infect water buffalo, but Salmonella isolates collected from this animal species have been poorly characterized. In the present study, the prevalence of Salmonella spp. in water buffalo calves affected by lethal gastroenteritis was assessed, and a polyphasic characterization of isolated strains of S. Typhimurium was performed. RESULTS: The microbiological analysis of the intestinal contents obtained from 248 water buffalo calves affected by lethal gastroenteritis exhibited a significant prevalence of Salmonella spp. (25%), characterized by different serovars, most frequently Typhimurium (21%), Muenster (11%), and Give (11%). The 13 S. Typhimurium isolates were all associated with enterocolitis characterized by severe damage of the intestine, and only sporadically isolated with another possible causative agent responsible for gastroenteritis, such as Cryptosporidium spp., Rotavirus or Clostridium perfringens. Other Salmonella isolates were mostly isolated from minor intestinal lesions, and often (78% of cases) isolated with other microorganisms, mainly toxinogenic Escherichia coli (35%), Cryptosporidium spp. (20%) and Rotavirus (10%). The S. Typhimurium strains were characterized by phage typing and further genotyped by polymerase chain reaction (PCR) detection of 24 virulence genes. The isolates exhibited nine different phage types and 10 different genetic profiles. Three monophasic S. Typhimurium (B:4,12:i:-) isolates were also found and characterized, displaying three different phage types and three different virulotypes. The molecular characterization was extended to the 7 S. Muenster and 7 S. Give isolates collected, indicating the existence of different virulotypes also within these serovars. Three representative strains of S. Typhimurium were tested in vivo in a mouse model of mixed infection. The most pathogenic strain was characterized by a high number of virulence factors and the presence of the locus agfA, coding for a thin aggregative fimbria. CONCLUSIONS: These results provide evidence that Salmonella is frequently associated with gastroenteritis in water buffalo calves, particularly S. Typhimurium. Moreover, the variety in the number and distribution of different virulence markers among the collected S. Typhimurium strains suggests that within this serovar there are different pathotypes potentially responsible for different clinical syndromes.",2012 Oct 25,"['Borriello, Giorgia', 'Lucibelli, Maria G', 'Pesciaroli, Michele', 'Carullo, Maria R', 'Graziani, Caterina', 'Ammendola, Serena', 'Battistoni, Andrea', 'Ercolini, Danilo', 'Pasquali, Paolo', 'Galiero, Giorgio']",BMC Vet Res,,,True
3695704554777889f8232a9ea086df70bf17ff58,PMC,Severe Childhood Malaria Syndromes Defined by Plasma Proteome Profiles,http://dx.doi.org/10.1371/journal.pone.0049778,PMC3514223,23226502,CC BY,"BACKGROUND: Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore it is important to understand the pathology underlying the development of CM and SMA, as opposed to uncomplicated malaria (UM). Different host responses to infection are likely to be reflected in plasma proteome-patterns that associate with clinical status and therefore provide indicators of the pathogenesis of these syndromes. METHODS AND FINDINGS: Plasma and comprehensive clinical data for discovery and validation cohorts were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, an urban and densely populated holoendemic malaria area in Nigeria. A total of 946 children participated in this study. Plasma was subjected to high-throughput proteomic profiling. Statistical pattern-recognition methods were used to find proteome-patterns that defined disease groups. Plasma proteome-patterns accurately distinguished children with CM and with SMA from those with UM, and from healthy or severely ill malaria-negative children. CONCLUSIONS: We report that an accurate definition of the major childhood malaria syndromes can be achieved using plasma proteome-patterns. Our proteomic data can be exploited to understand the pathogenesis of the different childhood severe malaria syndromes.",2012 Dec 4,"['Burté, Florence', 'Brown, Biobele J.', 'Orimadegun, Adebola E.', 'Ajetunmobi, Wasiu A.', 'Battaglia, Francesca', 'Ely, Barry K.', 'Afolabi, Nathaniel K.', 'Athanasakis, Dimitrios', 'Akinkunmi, Francis', 'Kowobari, Olayinka', 'Omokhodion, Samuel', 'Osinusi, Kikelomo', 'Akinbami, Felix O.', 'Shokunbi, Wuraola A.', 'Sodeinde, Olugbemiro', 'Fernandez-Reyes, Delmiro']",PLoS One,,,True
4f9d106c41459601d3804f9db29621c92c321921,PMC,Demographics and economic burden of un-owned cats and dogs in the UK: results of a 2010 census,http://dx.doi.org/10.1186/1746-6148-8-163,PMC3514250,22974242,CC BY,"BACKGROUND: The population of dogs and cats passing through rescue shelters may be subject to compromised welfare and increased susceptibility to disease. Little information exists to describe this population, its dynamics and associated management practices. The aim of this study was to carry out a census of un-owned cats and dogs in the UK in 2010, and to document the origins, destinations, husbandry and costs associated with the care of these animals. RESULTS: A sampling frame was constructed by searching the databases of publicly registered charities for England, Scotland and Wales, registers of breed rescues, and by internet searches of animal welfare websites. Overall, 2,352 contacts for 1,380 organisations were identified. All were sent a postal questionnaire asking for data on the number of dogs and cats housed, their origins and eventual outcomes, and details of husbandry between January 1(st) and December 31(st) 2010. For those which were registered charities (595), financial records were also obtained. A response rate of 38.8% was obtained. Overall, in 2010, 89,571 dogs and 156,826 cats entered the care of the participating organisations. Approximately half of these animals were relinquished by their owners. Other origins included being found as strays or confiscated for welfare purposes. Seventy-five per cent of dogs and 77.1% of cats were rehomed. The next most common outcome was euthanasia, accounting for 10.4% of dogs and 13.2% cats. For dogs and cats, 44.3% and 62% of participants respectively reported having a waiting list, which frequently exceeded the actual capacity of the facility. Over 19,000 people were involved in the care of these animals, on a paid or voluntary basis. Financial records were available for 519/595 (87.2%) of the registered charities, and their total expenditure in 2010 was £340 million. CONCLUSIONS: This study showed that a large number of animals become un-owned each year, which could have considerable implications for their welfare. Despite the resources expended, demand still exceeds capacity for many organisations, and a substantial number of both cats and dogs are euthanased, suggesting that further understanding of how and why these animals become un-owned is essential in order to target interventions.",2012 Sep 13,"['Stavisky, Jenny', 'Brennan, Marnie L', 'Downes, Martin', 'Dean, Rachel']",BMC Vet Res,,,True
3c8a38879c8d9910167b2dab37c2d98e17701141,PMC,Analysis of the swine tracheobronchial lymph node transcriptomic response to infection with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus,http://dx.doi.org/10.1186/1746-6148-8-208,PMC3514351,23110781,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen of swine worldwide. Emergence in 2006 of a novel highly pathogenic PRRSV (HP-PRRSV) isolate in China necessitated a comparative investigation into the host transcriptome response in tracheobronchial lymph nodes (TBLN) 13 days post-infection with HP-PRRSV rJXwn06, PRRSV strain VR-2332 or sham inocula. RNA from each was prepared for next-generation sequencing. Amplified library constructs were directly sequenced and a list of sequence transcripts and counts was generated using an RNAseq analysis pipeline to determine differential gene expression. Transcripts were annotated and relative abundance was calculated based upon the number of times a given transcript was represented in the library. RESULTS: Major changes in transcript abundance occurred in response to infection with either PRRSV strain, each with over 630 differentially expressed transcripts. The largest increase in transcript level for either virus versus sham-inoculated controls were three serum amyloid A2 acute-phase isoforms. However, the degree of up or down-regulation of transcripts following infection with HP-PRRSV rJXwn06 was greater than transcript changes observed with US PRRSV VR-2332. Also, of 632 significantly altered transcripts within the HP-PRRSV rJXwn06 library 55 were up-regulated and 69 were down-regulated more than 3-fold, whilst in the US PRRSV VR-2332 library only 4 transcripts were up-regulated and 116 were down-regulated more than 3-fold. CONCLUSIONS: The magnitude of differentially expressed gene profiles detected in HP-PRRSV rJXwn06 infected pigs as compared to VR-2332 infected pigs was consistent with the increased pathogenicity of the HP-PRRSV in vivo.",2012 Oct 30,"['Miller, Laura C', 'Fleming, Damarius', 'Arbogast, Andrew', 'Bayles, Darrell O', 'Guo, Baoqing', 'Lager, Kelly M', 'Henningson, Jamie N', 'Schlink, Sarah N', 'Yang, Han-Chun', 'Faaberg, Kay S', 'Kehrli, Marcus E']",BMC Vet Res,,,True
c19b92f638a71bdf631c296aee8d9fbfd4202034,PMC,FGF-9 accelerates epithelial invagination for ectodermal organogenesis in real time bioengineered organ manipulation,http://dx.doi.org/10.1186/1478-811X-10-34,PMC3515343,23176204,CC BY,"BACKGROUND: Epithelial invagination is important for initiation of ectodermal organogenesis. Although many factors regulate ectodermal organogenesis, there is not any report about their functions in real-time study. Electric cell-substrate impedance sensing (ECIS), a non-invasive, real-time surveillance system, had been used to detect changes in organ cell layer thickness through quantitative monitoring of the impedance of a cell-to-microelectrode interface over time. It was shown to be a good method for identifying significant real-time changes of cells. The purpose of this study is to establish a combined bioengineered organ-ECIS model for investigating the real time effects of fibroblast growth factor-9 (FGF-9) on epithelial invagination in bioengineered ectodermal organs. We dissected epithelial and mesenchymal cells from stage E14.5 murine molar tooth germs and identified the real-time effects of FGF-9 on epithelial-mesenchymal interactions using this combined bioengineered organ-ECIS model. RESULTS: Measurement of bioengineered ectodermal organ thickness showed that Fibroblast growth factor-9 (FGF-9) accelerates epithelial invagination in reaggregated mesenchymal cell layer within 3 days. Gene expression analysis revealed that FGF-9 stimulates and sustains early Ameloblastin and Amelogenin expression during odontogenesis. CONCLUSIONS: This is the first real-time study to show that, FGF-9 plays an important role in epithelial invagination and initiates ectodermal organogenesis. Based on these findings, we suggest FGF-9 can be applied for further study in ectodermal organ regeneration, and we also proposed that the ‘FGF-BMP balancing system’ is important for manipulating the morphogenesis of ectodermal organs. The combined bioengineered organ-ECIS model is a promising method for ectodermal organ engineering and regeneration research.",2012 Nov 23,"['Tai, Yun-Yuan', 'Chen, Rung-Shu', 'Lin, Yi', 'Ling, Thai-Yen', 'Chen, Min-Huey']",Cell Commun Signal,,,True
5a054a570f409d5c2006369f19addc98d024b6c1,PMC,Predicting pseudoknotted structures across two RNA sequences,http://dx.doi.org/10.1093/bioinformatics/bts575,PMC3516145,23044552,CC BY,"Motivation: Laboratory RNA structure determination is demanding and costly and thus, computational structure prediction is an important task. Single sequence methods for RNA secondary structure prediction are limited by the accuracy of the underlying folding model, if a structure is supported by a family of evolutionarily related sequences, one can be more confident that the prediction is accurate. RNA pseudoknots are functional elements, which have highly conserved structures. However, few comparative structure prediction methods can handle pseudoknots due to the computational complexity. Results: A comparative pseudoknot prediction method called DotKnot-PW is introduced based on structural comparison of secondary structure elements and H-type pseudoknot candidates. DotKnot-PW outperforms other methods from the literature on a hand-curated test set of RNA structures with experimental support. Availability: DotKnot-PW and the RNA structure test set are available at the web site http://dotknot.csse.uwa.edu.au/pw. Contact: janaspe@csse.uwa.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.",2012 Dec 1,"['Sperschneider, Jana', 'Datta, Amitava', 'Wise, Michael J.']",Bioinformatics,,,True
98c7a28b30c1faf0ddd330afa35e4329e4725cd8,PMC,Predicting pseudoknotted structures across two RNA sequences,http://dx.doi.org/10.1093/bioinformatics/bts575,PMC3516145,23044552,CC BY,"Motivation: Laboratory RNA structure determination is demanding and costly and thus, computational structure prediction is an important task. Single sequence methods for RNA secondary structure prediction are limited by the accuracy of the underlying folding model, if a structure is supported by a family of evolutionarily related sequences, one can be more confident that the prediction is accurate. RNA pseudoknots are functional elements, which have highly conserved structures. However, few comparative structure prediction methods can handle pseudoknots due to the computational complexity. Results: A comparative pseudoknot prediction method called DotKnot-PW is introduced based on structural comparison of secondary structure elements and H-type pseudoknot candidates. DotKnot-PW outperforms other methods from the literature on a hand-curated test set of RNA structures with experimental support. Availability: DotKnot-PW and the RNA structure test set are available at the web site http://dotknot.csse.uwa.edu.au/pw. Contact: janaspe@csse.uwa.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.",2012 Dec 1,"['Sperschneider, Jana', 'Datta, Amitava', 'Wise, Michael J.']",Bioinformatics,,,False
73e3d6f3f33c747bffbbb8122ab855bfb59676db,PMC,Exhaled Air Dispersion during Coughing with and without Wearing a Surgical or N95 Mask,http://dx.doi.org/10.1371/journal.pone.0050845,PMC3516468,23239991,CC BY,"OBJECTIVES: We compared the expelled air dispersion distances during coughing from a human patient simulator (HPS) lying at 45° with and without wearing a surgical mask or N95 mask in a negative pressure isolation room. METHODS: Airflow was marked with intrapulmonary smoke. Coughing bouts were generated by short bursts of oxygen flow at 650, 320, and 220L/min to simulate normal, mild and poor coughing efforts, respectively. The coughing jet was revealed by laser light-sheet and images were captured by high definition video. Smoke concentration in the plume was estimated from the light scattered by smoke particles. Significant exposure was arbitrarily defined where there was ≥ 20% of normalized smoke concentration. RESULTS: During normal cough, expelled air dispersion distances were 68, 30 and 15 cm along the median sagittal plane when the HPS wore no mask, a surgical mask and a N95 mask, respectively. In moderate lung injury, the corresponding air dispersion distances for mild coughing efforts were reduced to 55, 27 and 14 cm, respectively, p < 0.001. The distances were reduced to 30, 24 and 12 cm, respectively during poor coughing effort as in severe lung injury. Lateral dispersion distances during normal cough were 0, 28 and 15 cm when the HPS wore no mask, a surgical mask and a N95 mask, respectively. CONCLUSIONS: Normal cough produced a turbulent jet about 0.7 m towards the end of the bed from the recumbent subject. N95 mask was more effective than surgical mask in preventing expelled air leakage during coughing but there was still significant sideway leakage.",2012 Dec 5,"['Hui, David S.', 'Chow, Benny K.', 'Chu, Leo', 'Ng, Susanna S.', 'Lee, Nelson', 'Gin, Tony', 'Chan, Matthew T. V.']",PLoS One,,,True
42c1d88111ece7fdf4a80dc8ddb30be44b211d80,PMC,Rhesus Macaque Theta Defensins Suppress Inflammatory Cytokines and Enhance Survival in Mouse Models of Bacteremic Sepsis,http://dx.doi.org/10.1371/journal.pone.0051337,PMC3516535,23236475,CC BY,"Theta-defensins (θ-defensins) are macrocyclic antimicrobial peptides expressed in leukocytes of Old World monkeys. The peptides are broad spectrum microbicides in vitro and numerous θ-defensin isoforms have been identified in granulocytes of rhesus macaques and Olive baboons. Several mammalian α- and β-defensins, genetically related to θ-defensins, have proinflammatory and immune-activating properties that bridge innate and acquired immunity. In the current study we analyzed the immunoregulatory properties of rhesus θ-defensins 1–5 (RTDs 1–5). RTD-1, the most abundant θ-defensin in macaques, reduced the levels of TNF, IL-1α, IL-1β, IL-6, and IL-8 secreted by blood leukocytes stimulated by several TLR agonists. RTDs 1–5 suppressed levels of soluble TNF released by bacteria- or LPS-stimulated blood leukocytes and THP-1 monocytes. Despite their highly conserved conformation and amino acid sequences, the anti-TNF activities of RTDs 1–5 varied by as much as 10-fold. Systemically administered RTD-1 was non-toxic for BALB/c mice, and escalating intravenous doses were well tolerated and non-immunogenic in adult chimpanzees. The peptide was highly stable in serum and plasma. Single dose administration of RTD-1 at 5 mg/kg significantly improved survival of BALB/c mice with E. coli peritonitis and cecal ligation-and-puncture induced polymicrobial sepsis. Peptide treatment reduced serum levels of several inflammatory cytokines/chemokines in bacteremic animals. Collectively, these results indicate that the anti-inflammatory properties of θ-defensins in vitro and in vivo are mediated by the suppression of numerous proinflammatory cytokines and blockade of TNF release may be a primary effect.",2012 Dec 6,"['Schaal, Justin B.', 'Tran, Dat', 'Tran, Patti', 'Ösapay, George', 'Trinh, Katie', 'Roberts, Kevin D.', 'Brasky, Kathleen M.', 'Tongaonkar, Prasad', 'Ouellette, André J.', 'Selsted, Michael E.']",PLoS One,,,True
8984416a285ced3a8855c5b4a473d02ab50e73d0,PMC,Three-Dimensional Architecture and Biogenesis of Membrane Structures Associated with Hepatitis C Virus Replication,http://dx.doi.org/10.1371/journal.ppat.1003056,PMC3516559,23236278,CC BY,"All positive strand RNA viruses are known to replicate their genomes in close association with intracellular membranes. In case of the hepatitis C virus (HCV), a member of the family Flaviviridae, infected cells contain accumulations of vesicles forming a membranous web (MW) that is thought to be the site of viral RNA replication. However, little is known about the biogenesis and three-dimensional structure of the MW. In this study we used a combination of immunofluorescence- and electron microscopy (EM)-based methods to analyze the membranous structures induced by HCV in infected cells. We found that the MW is derived primarily from the endoplasmic reticulum (ER) and contains markers of rough ER as well as markers of early and late endosomes, COP vesicles, mitochondria and lipid droplets (LDs). The main constituents of the MW are single and double membrane vesicles (DMVs). The latter predominate and the kinetic of their appearance correlates with kinetics of viral RNA replication. DMVs are induced primarily by NS5A whereas NS4B induces single membrane vesicles arguing that MW formation requires the concerted action of several HCV replicase proteins. Three-dimensional reconstructions identify DMVs as protrusions from the ER membrane into the cytosol, frequently connected to the ER membrane via a neck-like structure. In addition, late in infection multi-membrane vesicles become evident, presumably as a result of a stress-induced reaction. Thus, the morphology of the membranous rearrangements induced in HCV-infected cells resemble those of the unrelated picorna-, corona- and arteriviruses, but are clearly distinct from those of the closely related flaviviruses. These results reveal unexpected similarities between HCV and distantly related positive-strand RNA viruses presumably reflecting similarities in cellular pathways exploited by these viruses to establish their membranous replication factories.",2012 Dec 6,"['Romero-Brey, Inés', 'Merz, Andreas', 'Chiramel, Abhilash', 'Lee, Ji-Young', 'Chlanda, Petr', 'Haselman, Uta', 'Santarella-Mellwig, Rachel', 'Habermann, Anja', 'Hoppe, Simone', 'Kallis, Stephanie', 'Walther, Paul', 'Antony, Claude', 'Krijnse-Locker, Jacomine', 'Bartenschlager, Ralf']",PLoS Pathog,,,True
0b05d3ede3351f8b3edb22c74b0cfe933ba408c1,PMC,Cathepsin B & L Are Not Required for Ebola Virus Replication,http://dx.doi.org/10.1371/journal.pntd.0001923,PMC3516577,23236527,CC0,"Ebola virus (EBOV), family Filoviridae, emerged in 1976 on the African continent. Since then it caused several outbreaks of viral hemorrhagic fever in humans with case fatality rates up to 90% and remains a serious Public Health concern and biothreat pathogen. The most pathogenic and best-studied species is Zaire ebolavirus (ZEBOV). EBOV encodes one viral surface glycoprotein (GP), which is essential for replication, a determinant of pathogenicity and an important immunogen. GP mediates viral entry through interaction with cellular surface molecules, which results in the uptake of virus particles via macropinocytosis. Later in this pathway endosomal acidification activates the cysteine proteases Cathepsin B and L (CatB, CatL), which have been shown to cleave ZEBOV-GP leading to subsequent exposure of the putative receptor-binding and fusion domain and productive infection. We studied the effect of CatB and CatL on in vitro and in vivo replication of EBOV. Similar to previous findings, our results show an effect of CatB, but not CatL, on ZEBOV entry into cultured cells. Interestingly, cell entry by other EBOV species (Bundibugyo, Côte d'Ivoire, Reston and Sudan ebolavirus) was independent of CatB or CatL as was EBOV replication in general. To investigate whether CatB and CatL have a role in vivo during infection, we utilized the mouse model for ZEBOV. Wild-type (control), catB(−/−) and catL(−/−) mice were equally susceptible to lethal challenge with mouse-adapted ZEBOV with no difference in virus replication and time to death. In conclusion, our results show that CatB and CatL activity is not required for EBOV replication. Furthermore, EBOV glycoprotein cleavage seems to be mediated by an array of proteases making targeted therapeutic approaches difficult.",2012 Dec 6,"['Marzi, Andrea', 'Reinheckel, Thomas', 'Feldmann, Heinz']",PLoS Negl Trop Dis,,,True
aaf71afd1d3f2d1ee34ba2fb720aca20c35a303b,PMC,Digital Surveillance: A Novel Approach to Monitoring the Illegal Wildlife Trade,http://dx.doi.org/10.1371/journal.pone.0051156,PMC3517447,23236444,CC BY,"A dearth of information obscures the true scale of the global illegal trade in wildlife. Herein, we introduce an automated web crawling surveillance system developed to monitor reports on illegally traded wildlife. A resource for enforcement officials as well as the general public, the freely available website, http://www.healthmap.org/wildlifetrade, provides a customizable visualization of worldwide reports on interceptions of illegally traded wildlife and wildlife products. From August 1, 2010 to July 31, 2011, publicly available English language illegal wildlife trade reports from official and unofficial sources were collected and categorized by location and species involved. During this interval, 858 illegal wildlife trade reports were collected from 89 countries. Countries with the highest number of reports included India (n = 146, 15.6%), the United States (n = 143, 15.3%), South Africa (n = 75, 8.0%), China (n = 41, 4.4%), and Vietnam (n = 37, 4.0%). Species reported as traded or poached included elephants (n = 107, 12.5%), rhinoceros (n = 103, 12.0%), tigers (n = 68, 7.9%), leopards (n = 54, 6.3%), and pangolins (n = 45, 5.2%). The use of unofficial data sources, such as online news sites and social networks, to collect information on international wildlife trade augments traditional approaches drawing on official reporting and presents a novel source of intelligence with which to monitor and collect news in support of enforcement against this threat to wildlife conservation worldwide.",2012 Dec 7,"['Sonricker Hansen, Amy L.', 'Li, Annie', 'Joly, Damien', 'Mekaru, Sumiko', 'Brownstein, John S.']",PLoS One,,,True
64c22236bc20680680fffab70eedef1f21641bd0,PMC,Intranasal Administration of dsRNA Analog Poly(I:C) Induces Interferon-α Receptor-Dependent Accumulation of Antigen Experienced T Cells in the Airways,http://dx.doi.org/10.1371/journal.pone.0051351,PMC3517467,23236482,CC BY,"Polyriboinosinic-polyribocytoidylic acid (pIC), a synthetic dsRNA, acts as an adjuvant that boosts immune responses and protection. Intranasal (IN) administration of pIC has recently been used to adjuvant influenza virus vaccines; however, the effects of IN pIC administration on pulmonary T cell responses remain unclear. Here we show that a single IN administered dose of dsRNA into mice induced local Th1 chemokine production in the lungs and airways, and generated a biphasic and sustained migration of T lymphocytes to the airways. Furthermore, IN pIC-induced chemokine production and T cell recruitment to the airways were interferon-α receptor (IFNAR) signaling dependent. The effect of dsRNA on T cell recruitment to the airways was also dependent on the presence of high molecular weight (HMW) pIC, as a low molecular weight (LMW) pIC preparation known to only interact with TLR3 did not elicit the same effect on T cell migration to the airways, suggesting that the observed effects were dependent upon dsRNA recognition by multiple pattern recognition receptors (PPRs). IN pIC was additionally capable of stimulating low levels of T cell proliferation in the draining lymph nodes approximately 4–6 days after treatment that preceded a small population of de-novo T cells found in the airways by day 10. Taken together, these results demonstrate that the adjuvant effect of IN pIC that results in enhanced T cell proliferation and sustained T cell recruitment to the airways requires multiple PRRs and IFNAR signaling.",2012 Dec 7,"['McNally, Beth', 'Willette, Meredith', 'Ye, Fang', 'Partida-Sanchez, Santiago', 'Flaño, Emilio']",PLoS One,,,True
380e9f8318abdddde5c3c6b30802f48f4d3540c4,PMC,National inventory of emergency departments in Singapore,http://dx.doi.org/10.1186/1865-1380-5-38,PMC3518169,23114079,CC BY,"BACKGROUND: Emergency departments (EDs) are the basic units of emergency care. We performed a national inventory of all Singapore EDs and describe their characteristics and capabilities. METHODS: Singapore EDs accessible to the general public 24/7 were surveyed using the National ED Inventories instrument ( http://www.emnet-nedi.org). ED staff members were asked about ED characteristics with reference to calendar year 2007. RESULTS: Fourteen EDs participated (100% response). All EDs were located in hospitals, and most (92%) were independent departments. One was a psychiatric ED; the rest were general EDs. Among general EDs, all had a contiguous layout, with medical and surgical care provided in one area. All but two EDs saw both adults and children; one ED was adult-only, and the other saw only children. Six were in the public sector and seven in private health-care institutions, with public EDs seeing the majority (78%) of ED patients. Each private ED had an annual patient census of <30,000. These EDs received 2% of ambulances and had an inpatient admission rate of 7%. Each public ED had an annual census of >60,000. They received 98% of ambulances and had an inpatient admission rate of 30%. Two public EDs reported being overcapacity; no private EDs did. For both public and private EDs, availability of consultant resources in EDs was high, while technological resources varied. CONCLUSION: Characteristics and capabilities of Singapore EDs varied and were largely dependent on whether they are in public or private hospitals. This initial inventory establishes a benchmark to further monitor the development of emergency care in Singapore.",2012 Oct 31,"['Wen, Leana S', 'Venkataraman, Anantharaman', 'Sullivan, Ashley F', 'Camargo, Carlos A']",Int J Emerg Med,,,True
0e3da58a0d46d88ee542720cc9e1f594a3d69a79,PMC,The influence of climatic conditions on the transmission dynamics of the 2009 A/H1N1 influenza pandemic in Chile,http://dx.doi.org/10.1186/1471-2334-12-298,PMC3518181,23148597,CC BY,"BACKGROUND: The role of demographic factors, climatic conditions, school cycles, and connectivity patterns in shaping the spatio-temporal dynamics of pandemic influenza is not clearly understood. Here we analyzed the spatial, age and temporal evolution of the 2009 A/H1N1 influenza pandemic in Chile, a southern hemisphere country covering a long and narrow strip comprising latitudes 17°S to 56°S. METHODS: We analyzed the dissemination patterns of the 2009 A/H1N1 pandemic across 15 regions of Chile based on daily hospitalizations for severe acute respiratory disease and laboratory confirmed A/H1N1 influenza infection from 01-May to 31-December, 2009. We explored the association between timing of pandemic onset and peak pandemic activity and several geographical and demographic indicators, school vacations, climatic factors, and international passengers. We also estimated the reproduction number (R) based on the growth rate of the exponential pandemic phase by date of symptoms onset, estimated using maximum likelihood methods. RESULTS: While earlier pandemic onset was associated with larger population size, there was no association with connectivity, demographic, school or climatic factors. In contrast, there was a latitudinal gradient in peak pandemic timing, representing a 16-39-day lag in disease activity from the southern regions relative to the northernmost region (P < 0.001). Geographical differences in latitude of Chilean regions, maximum temperature and specific humidity explained 68.5% of the variability in peak timing (P = 0.01). In addition, there was a decreasing gradient in reproduction number from south to north Chile (P < 0.0001). The regional mean R estimates were 1.6-2.0, 1.3-1.5, and 1.2-1.3 for southern, central and northern regions, respectively, which were not affected by the winter vacation period. CONCLUSIONS: There was a lag in the period of most intense 2009 pandemic influenza activity following a South to North traveling pattern across regions of Chile, significantly associated with geographical differences in minimum temperature and specific humidity. The latitudinal gradient in timing of pandemic activity was accompanied by a gradient in reproduction number (P < 0.0001). Intensified surveillance strategies in colder and drier southern regions could lead to earlier detection of pandemic influenza viruses and improved control outcomes.",2012 Nov 13,"['Chowell, Gerardo', 'Towers, Sherry', 'Viboud, Cécile', 'Fuentes, Rodrigo', 'Sotomayor, Viviana', 'Simonsen, Lone', 'Miller, Mark A', 'Lima, Mauricio', 'Villarroel, Claudia', 'Chiu, Monica', 'Villarroel, Jose E', 'Olea, Andrea']",BMC Infect Dis,,,True
4dfa5a3533ef3b79abb871f4b4132f8b654a52eb,PMC,The influence of climatic conditions on the transmission dynamics of the 2009 A/H1N1 influenza pandemic in Chile,http://dx.doi.org/10.1186/1471-2334-12-298,PMC3518181,23148597,CC BY,"BACKGROUND: The role of demographic factors, climatic conditions, school cycles, and connectivity patterns in shaping the spatio-temporal dynamics of pandemic influenza is not clearly understood. Here we analyzed the spatial, age and temporal evolution of the 2009 A/H1N1 influenza pandemic in Chile, a southern hemisphere country covering a long and narrow strip comprising latitudes 17°S to 56°S. METHODS: We analyzed the dissemination patterns of the 2009 A/H1N1 pandemic across 15 regions of Chile based on daily hospitalizations for severe acute respiratory disease and laboratory confirmed A/H1N1 influenza infection from 01-May to 31-December, 2009. We explored the association between timing of pandemic onset and peak pandemic activity and several geographical and demographic indicators, school vacations, climatic factors, and international passengers. We also estimated the reproduction number (R) based on the growth rate of the exponential pandemic phase by date of symptoms onset, estimated using maximum likelihood methods. RESULTS: While earlier pandemic onset was associated with larger population size, there was no association with connectivity, demographic, school or climatic factors. In contrast, there was a latitudinal gradient in peak pandemic timing, representing a 16-39-day lag in disease activity from the southern regions relative to the northernmost region (P < 0.001). Geographical differences in latitude of Chilean regions, maximum temperature and specific humidity explained 68.5% of the variability in peak timing (P = 0.01). In addition, there was a decreasing gradient in reproduction number from south to north Chile (P < 0.0001). The regional mean R estimates were 1.6-2.0, 1.3-1.5, and 1.2-1.3 for southern, central and northern regions, respectively, which were not affected by the winter vacation period. CONCLUSIONS: There was a lag in the period of most intense 2009 pandemic influenza activity following a South to North traveling pattern across regions of Chile, significantly associated with geographical differences in minimum temperature and specific humidity. The latitudinal gradient in timing of pandemic activity was accompanied by a gradient in reproduction number (P < 0.0001). Intensified surveillance strategies in colder and drier southern regions could lead to earlier detection of pandemic influenza viruses and improved control outcomes.",2012 Nov 13,"['Chowell, Gerardo', 'Towers, Sherry', 'Viboud, Cécile', 'Fuentes, Rodrigo', 'Sotomayor, Viviana', 'Simonsen, Lone', 'Miller, Mark A', 'Lima, Mauricio', 'Villarroel, Claudia', 'Chiu, Monica', 'Villarroel, Jose E', 'Olea, Andrea']",BMC Infect Dis,,,True
ea7ae35a6203f68c29d8aa305a9d89ba8c76d284,PMC,Diagnostic issues and capabilities in 48 isolation facilities in 16 European countries: data from EuroNHID surveys,http://dx.doi.org/10.1186/1756-0500-5-527,PMC3519610,23009598,CC BY,"BACKGROUND: Highly infectious diseases (HIDs) are defined as being transmissible from person to person, causing life-threatening illnesses and presenting a serious public health hazard. The sampling, handling and transport of specimens from patients with HIDs present specific bio-safety concerns. FINDINGS: The European Network for HID project aimed to record, in a cross-sectional study, the infection control capabilities of referral centers for HIDs across Europe and assesses the level of achievement to previously published guidelines. In this paper, we report the current diagnostic capabilities and bio-safety measures applied to diagnostic procedures in these referral centers. Overall, 48 isolation facilities in 16 European countries were evaluated. Although 81% of these referral centers are located near a biosafety level 3 laboratory, 11% and 31% of them still performed their microbiological and routine diagnostic analyses, respectively, without bio-safety measures. CONCLUSIONS: The discrepancies among the referral centers surveyed between the level of practices and the European Network of Infectious Diseases (EUNID) recommendations have multiple reasons of which the interest of the individuals in charge and the investment they put in preparedness to emerging outbreaks. Despite the fact that the less prepared centers can improve by just updating their practice and policies any support to help them to achieve an acceptable level of biosecurity is welcome.",2012 Sep 25,"['Thiberville, Simon-Djamel', 'Schilling, Stefan', 'De Iaco, Giuseppina', 'Fusco, Francesco Maria', 'Thomson, Gail', 'Maltezou, Helen C', 'Gottschalk, Rene', 'Brodt, Reinhard H', 'Bannister, Barbara', 'Puro, Vincenzo', 'Ippolito, Giuseppe', 'Brouqui, Philippe']",BMC Res Notes,,,True
7f911fcc63f431561d8dc09ed831ce558ca2d773,PMC,Identification of a conserved linear B-cell epitope in the M protein of porcine epidemic diarrhea virus,http://dx.doi.org/10.1186/1743-422X-9-225,PMC3519612,23025700,CC BY,"BACKGROUND: The major structural protein of coronaviruses, the membrane (M) protein, can elicit the formation of protective antibodies, but little information is available about the M protein of porcine epidemic diarrhea virus (PEDV). Identification of epitopes on the PEDV M protein will be helpful in the elucidation of the antigenic properties of this protein. RESULTS: One hybridoma cell line secreting anti-M protein monoclonal antibody (McAb) was generated and designated 4D4. To map the epitopes on the PEDV M protein, a total of 17 partially overlapping fragments covering the C-terminus of M protein were expressed as fusion proteins with a 6×His tag or a GST tag. A linear motif, (193)TGWAFYVR(200), was identified by enzyme-linked immunosorbent assay (ELISA) and western blot (WB) analysis using McAb 4D4. The motif (195)WAFYVR(200) was the minimal requirement for reactivity, as demonstrated by removing amino acids individually from both ends of the motif (193)TGWAFYVR(200). The result of WB analysis showed that the 4D4-defined epitope could be recognized by PEDV-positive serum, but not transmissible gastroenteritis virus (TGEV)-positive serum. Furthermore, this epitope was highly conserved among different PEDV strains, as shown by alignment and comparison of sequences. CONCLUSION: A McAb, 4D4, directed against the M protein of PEDV, was obtained, and the 4D4-defined minimal epitope sequence was (195)WAFYVR(200). The McAb could serve as a candidate for development of a McAb-based antigen capture ELISA for detection of PEDV. The epitope identified provides a basis for the development of epitope-based differential diagnostic techniques and may be useful in the design of epitope-based vaccines.",2012 Oct 1,"['Zhang, Zhibang', 'Chen, Jianfei', 'Shi, Hongyan', 'Chen, Xiaojin', 'Shi, Da', 'Feng, Li', 'Yang, Bin']",Virol J,,,True
b5421a028a9ff8b2f36ad9be3c51d3d0cb78ddd6,PMC,"Nullbasic, a Potent Anti-HIV Tat Mutant, Induces CRM1-Dependent Disruption of HIV Rev Trafficking",http://dx.doi.org/10.1371/journal.pone.0051466,PMC3519632,23251541,CC BY,"Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, establishing that redistribution of Rev by Nullbasic is not due to direct interaction between the two proteins. Rather, Nullbasic affects subcellular localization of cellular proteins that regulate Rev trafficking. In particular, Nullbasic induced redistribution of exportin 1 (CRM1), nucleophosmin (B23) and nucleolin (C23) from the nucleolus to the nucleus when Rev was coexpressed, but never in its absence. Inhibition of the Rev:CRM1 interaction by leptomycin B or a non-interacting RevM10 mutant completely blocked redistribution of Rev by Nullbasic. Finally, Nullbasic did not inhibit importin β- or transportin 1-mediated nuclear import, suggesting that cytoplasmic accumulation of Rev was due to increased export by CRM1. Overall, our data support the conclusion that CRM1-dependent subcellular redistribution of Rev from the nucleolus by Nullbasic is not through general perturbation of either nuclear import or export. Rather, Nullbasic appears to interact with and disrupt specific components of a Rev trafficking complex required for its nucleocytoplasmic shuttling and, in particular, its nucleolar accumulation.",2012 Dec 10,"['Lin, Min-Hsuan', 'Sivakumaran, Haran', 'Apolloni, Ann', 'Wei, Ting', 'Jans, David A.', 'Harrich, David']",PLoS One,,,True
2ab6b5e2628c1979ae2e65f9a0f9870cb3773d61,PMC,"Comparison of three multiplex PCR assays for the detection of respiratory viral infections: evaluation of xTAG respiratory virus panel fast assay, RespiFinder 19 assay and RespiFinder SMART 22 assay",http://dx.doi.org/10.1186/1471-2334-12-163,PMC3519643,22828244,CC BY,"BACKGROUND: A broad spectrum of pathogens is causative for respiratory tract infections, but symptoms are mostly similar. Therefore, the identification of the causative viruses and bacteria is only feasible using multiplex PCR or several monoplex PCR tests in parallel. METHODS: The analytical sensitivity of three multiplex PCR assays, RespiFinder-19, RespiFinder-SMART-22 and xTAG-Respiratory-Virus-Panel-Fast-Assay (RVP), were compared to monoplex real-time PCR with quantified standardized control material. All assays include the most common respiratory pathogens. RESULTS: To compare the analytical sensitivity of the multiplex assays, samples were inoculated with 13 different quantified viruses in the range of 10(1) to 10(5) copies/ml. Concordant results were received for rhinovirus, whereas the RVP detected influenzavirus, RSV and hMPV more frequently in low concentrations. The RespiFinder-19 and the RespiFinder-SMART-22 showed a higher analytical sensitivity for adenoviruses and coronaviruses, whereas the RVP was incapable to detect adenovirus and coronavirus in concentrations of 10(4) copies/ml. The RespiFinder-19 and RespiFinder-SMART-22A did not detect influenzaviruses (10(4) copies/ml) and RSV (10(3) copies/ml). The detection of all 13 viruses in one sample was only achieved using monoplex PCR. To analyze possible competitive amplification reactions between the different viruses, samples were further inoculated with only 4 different viruses in one sample. Compared to the detection of 13 viruses in parallel, only a few differences were found. The incidence of respiratory viruses was compared in tracheal secretion (TS) samples (n = 100) of mechanically ventilated patients in winter (n = 50) and summer (n = 50). In winter, respiratory viruses were detected in 32 TS samples (64%) by RespiFinder-19, whereas the detection rate with RVP was only 22%. The most frequent viruses were adenovirus (32%) and PIV-2 (20%). Multiple infections were detected in 16 TS samples (32%) by RespiFinder-19. Fewer infections were found in summer (RespiFinder-19: 20%; RVP: 6%). All positive results were verified using monoplex PCR. CONCLUSIONS: Multiplex PCR tests have a broad spectrum of pathogens to test at a time. Analysis of multiple inoculated samples revealed a different focus of the detected virus types by the three assays. Analysis of clinical samples showed a high concordance of detected viruses by the RespiFinder-19 compared to monoplex tests.",2012 Jul 24,"['Dabisch-Ruthe, Mareike', 'Vollmer, Tanja', 'Adams, Ortwin', 'Knabbe, Cornelius', 'Dreier, Jens']",BMC Infect Dis,,,True
a88ec297fe59d6c950ea8123ddda210a7b134032,PMC,A MultiSite Gateway(TM )vector set for the functional analysis of genes in the model Saccharomyces cerevisiae,http://dx.doi.org/10.1186/1471-2199-13-30,PMC3519679,22994806,CC BY,"BACKGROUND: Recombinatorial cloning using the Gateway(TM) technology has been the method of choice for high-throughput omics projects, resulting in the availability of entire ORFeomes in Gateway(TM) compatible vectors. The MultiSite Gateway(TM) system allows combining multiple genetic fragments such as promoter, ORF and epitope tag in one single reaction. To date, this technology has not been accessible in the yeast Saccharomyces cerevisiae, one of the most widely used experimental systems in molecular biology, due to the lack of appropriate destination vectors. RESULTS: Here, we present a set of three-fragment MultiSite Gateway(TM) destination vectors that have been developed for gene expression in S. cerevisiae and that allow the assembly of any promoter, open reading frame, epitope tag arrangement in combination with any of four auxotrophic markers and three distinct replication mechanisms. As an example of its applicability, we used yeast three-hybrid to provide evidence for the assembly of a ternary complex of plant proteins involved in jasmonate signalling and consisting of the JAZ, NINJA and TOPLESS proteins. CONCLUSION: Our vectors make MultiSite Gateway(TM) cloning accessible in S. cerevisiae and implement a fast and versatile cloning method for the high-throughput functional analysis of (heterologous) proteins in one of the most widely used model organisms for molecular biology research.",2012 Sep 20,"['Nagels Durand, Astrid', 'Moses, Tessa', 'De Clercq, Rebecca', 'Goossens, Alain', 'Pauwels, Laurens']",BMC Mol Biol,,,True
417fd2b2eba2473029f35d664f1bc72e03022eb1,PMC,Respiratory viruses from hospitalized children with severe pneumonia in the Philippines,http://dx.doi.org/10.1186/1471-2334-12-267,PMC3519714,23092190,CC BY,"BACKGROUND: Pneumonia remains a leading cause of child death in developing countries. The viruses in severe pneumonia remain poorly defined. METHODS: The study was conducted at the Eastern Visayas Regional Medical Center in Tacloban City, Philippines from May 2008 to May 2009. Patients aged 8 days to 13 years old who were admitted to the Department of Pediatrics with severe pneumonia were enrolled for the study. Upon admission, polymerase chain reaction was performed using nasopharyngeal swabs and blood cultures to detect respiratory viruses and bacteria, respectively. RESULT: Among the 819 patients enrolled, at least one virus was detected in 501 cases (61.2%). In addition, 423 cases were positive for a single virus while bacteria were detected in the blood culture sample of 31 cases. The most commonly detected viruses were human rhinoviruses (n = 189), including types A (n = 103), B (n = 17), and C (n = 69), and respiratory syncytial virus (RSV) (n = 165). Novel viruses such as human metapneumovirus, human coronavirus NL63, human bocavirus, and human polyomaviruses WU and KI were also detected. There were 70 deaths, and one or more viruses were detected in 35 (50%) of these cases. Positivity only for influenza A virus (OR = 4.3, 95% CI = 1.3-14.6) was significantly associated with fatal outcome. From the blood culture, Burkholderia cepacia group (n = 9), Streptococcus pneumoniae (n = 4), Staphylococcus aureus (n = 4), Haemophilus influenzae (n = 1), and Salmonella C1 (n = 1) were also isolated. CONCLUSION: Viruses were commonly detected in children with severe pneumonia in the Philippines. Hence, viral etiologies should be considered while developing better effective strategies to reduce child pneumonia-related deaths in developing countries.",2012 Oct 23,"['Suzuki, Akira', 'Lupisan, Socorro', 'Furuse, Yuki', 'Fuji, Naoko', 'Saito, Mariko', 'Tamaki, Raita', 'Galang, Hazel', 'Sombrero, Lydia', 'Mondoy, Melisa', 'Aniceto, Rapunzel', 'Olveda, Remigio', 'Oshitani, Hitoshi']",BMC Infect Dis,,,True
3ade01fb8514f2846a69bcfe3d6eb552b4cd24d0,PMC,Respiratory viruses from hospitalized children with severe pneumonia in the Philippines,http://dx.doi.org/10.1186/1471-2334-12-267,PMC3519714,23092190,CC BY,"BACKGROUND: Pneumonia remains a leading cause of child death in developing countries. The viruses in severe pneumonia remain poorly defined. METHODS: The study was conducted at the Eastern Visayas Regional Medical Center in Tacloban City, Philippines from May 2008 to May 2009. Patients aged 8 days to 13 years old who were admitted to the Department of Pediatrics with severe pneumonia were enrolled for the study. Upon admission, polymerase chain reaction was performed using nasopharyngeal swabs and blood cultures to detect respiratory viruses and bacteria, respectively. RESULT: Among the 819 patients enrolled, at least one virus was detected in 501 cases (61.2%). In addition, 423 cases were positive for a single virus while bacteria were detected in the blood culture sample of 31 cases. The most commonly detected viruses were human rhinoviruses (n = 189), including types A (n = 103), B (n = 17), and C (n = 69), and respiratory syncytial virus (RSV) (n = 165). Novel viruses such as human metapneumovirus, human coronavirus NL63, human bocavirus, and human polyomaviruses WU and KI were also detected. There were 70 deaths, and one or more viruses were detected in 35 (50%) of these cases. Positivity only for influenza A virus (OR = 4.3, 95% CI = 1.3-14.6) was significantly associated with fatal outcome. From the blood culture, Burkholderia cepacia group (n = 9), Streptococcus pneumoniae (n = 4), Staphylococcus aureus (n = 4), Haemophilus influenzae (n = 1), and Salmonella C1 (n = 1) were also isolated. CONCLUSION: Viruses were commonly detected in children with severe pneumonia in the Philippines. Hence, viral etiologies should be considered while developing better effective strategies to reduce child pneumonia-related deaths in developing countries.",2012 Oct 23,"['Suzuki, Akira', 'Lupisan, Socorro', 'Furuse, Yuki', 'Fuji, Naoko', 'Saito, Mariko', 'Tamaki, Raita', 'Galang, Hazel', 'Sombrero, Lydia', 'Mondoy, Melisa', 'Aniceto, Rapunzel', 'Olveda, Remigio', 'Oshitani, Hitoshi']",BMC Infect Dis,,,False
414a9d49055b96830b86bd3b4cb7b9e6973d05f6,PMC,Respiratory viruses from hospitalized children with severe pneumonia in the Philippines,http://dx.doi.org/10.1186/1471-2334-12-267,PMC3519714,23092190,CC BY,"BACKGROUND: Pneumonia remains a leading cause of child death in developing countries. The viruses in severe pneumonia remain poorly defined. METHODS: The study was conducted at the Eastern Visayas Regional Medical Center in Tacloban City, Philippines from May 2008 to May 2009. Patients aged 8 days to 13 years old who were admitted to the Department of Pediatrics with severe pneumonia were enrolled for the study. Upon admission, polymerase chain reaction was performed using nasopharyngeal swabs and blood cultures to detect respiratory viruses and bacteria, respectively. RESULT: Among the 819 patients enrolled, at least one virus was detected in 501 cases (61.2%). In addition, 423 cases were positive for a single virus while bacteria were detected in the blood culture sample of 31 cases. The most commonly detected viruses were human rhinoviruses (n = 189), including types A (n = 103), B (n = 17), and C (n = 69), and respiratory syncytial virus (RSV) (n = 165). Novel viruses such as human metapneumovirus, human coronavirus NL63, human bocavirus, and human polyomaviruses WU and KI were also detected. There were 70 deaths, and one or more viruses were detected in 35 (50%) of these cases. Positivity only for influenza A virus (OR = 4.3, 95% CI = 1.3-14.6) was significantly associated with fatal outcome. From the blood culture, Burkholderia cepacia group (n = 9), Streptococcus pneumoniae (n = 4), Staphylococcus aureus (n = 4), Haemophilus influenzae (n = 1), and Salmonella C1 (n = 1) were also isolated. CONCLUSION: Viruses were commonly detected in children with severe pneumonia in the Philippines. Hence, viral etiologies should be considered while developing better effective strategies to reduce child pneumonia-related deaths in developing countries.",2012 Oct 23,"['Suzuki, Akira', 'Lupisan, Socorro', 'Furuse, Yuki', 'Fuji, Naoko', 'Saito, Mariko', 'Tamaki, Raita', 'Galang, Hazel', 'Sombrero, Lydia', 'Mondoy, Melisa', 'Aniceto, Rapunzel', 'Olveda, Remigio', 'Oshitani, Hitoshi']",BMC Infect Dis,,,False
151812be7cb8160939baf6896a5c4f6fdfbfd973,PMC,Respiratory viruses from hospitalized children with severe pneumonia in the Philippines,http://dx.doi.org/10.1186/1471-2334-12-267,PMC3519714,23092190,CC BY,"BACKGROUND: Pneumonia remains a leading cause of child death in developing countries. The viruses in severe pneumonia remain poorly defined. METHODS: The study was conducted at the Eastern Visayas Regional Medical Center in Tacloban City, Philippines from May 2008 to May 2009. Patients aged 8 days to 13 years old who were admitted to the Department of Pediatrics with severe pneumonia were enrolled for the study. Upon admission, polymerase chain reaction was performed using nasopharyngeal swabs and blood cultures to detect respiratory viruses and bacteria, respectively. RESULT: Among the 819 patients enrolled, at least one virus was detected in 501 cases (61.2%). In addition, 423 cases were positive for a single virus while bacteria were detected in the blood culture sample of 31 cases. The most commonly detected viruses were human rhinoviruses (n = 189), including types A (n = 103), B (n = 17), and C (n = 69), and respiratory syncytial virus (RSV) (n = 165). Novel viruses such as human metapneumovirus, human coronavirus NL63, human bocavirus, and human polyomaviruses WU and KI were also detected. There were 70 deaths, and one or more viruses were detected in 35 (50%) of these cases. Positivity only for influenza A virus (OR = 4.3, 95% CI = 1.3-14.6) was significantly associated with fatal outcome. From the blood culture, Burkholderia cepacia group (n = 9), Streptococcus pneumoniae (n = 4), Staphylococcus aureus (n = 4), Haemophilus influenzae (n = 1), and Salmonella C1 (n = 1) were also isolated. CONCLUSION: Viruses were commonly detected in children with severe pneumonia in the Philippines. Hence, viral etiologies should be considered while developing better effective strategies to reduce child pneumonia-related deaths in developing countries.",2012 Oct 23,"['Suzuki, Akira', 'Lupisan, Socorro', 'Furuse, Yuki', 'Fuji, Naoko', 'Saito, Mariko', 'Tamaki, Raita', 'Galang, Hazel', 'Sombrero, Lydia', 'Mondoy, Melisa', 'Aniceto, Rapunzel', 'Olveda, Remigio', 'Oshitani, Hitoshi']",BMC Infect Dis,,,False
cb43de0358c05aba59dfb4957432fc2cbe31b30e,PMC,Antagonistic Pleiotropy and Fitness Trade-Offs Reveal Specialist and Generalist Traits in Strains of Canine Distemper Virus,http://dx.doi.org/10.1371/journal.pone.0050955,PMC3519774,23239996,CC BY,"Theoretically, homogeneous environments favor the evolution of specialists whereas heterogeneous environments favor generalists. Canine distemper is a multi-host carnivore disease caused by canine distemper virus (CDV). The described cell receptor of CDV is SLAM (CD150). Attachment of CDV hemagglutinin protein (CDV-H) to this receptor facilitates fusion and virus entry in cooperation with the fusion protein (CDV-F). We investigated whether CDV strains co-evolved in the large, homogeneous domestic dog population exhibited specialist traits, and strains adapted to the heterogeneous environment of smaller populations of different carnivores exhibited generalist traits. Comparison of amino acid sequences of the SLAM binding region revealed higher similarity between sequences from Canidae species than to sequences from other carnivore families. Using an in vitro assay, we quantified syncytia formation mediated by CDV-H proteins from dog and non-dog CDV strains in cells expressing dog, lion or cat SLAM. CDV-H proteins from dog strains produced significantly higher values with cells expressing dog SLAM than with cells expressing lion or cat SLAM. CDV-H proteins from strains of non-dog species produced similar values in all three cell types, but lower values in cells expressing dog SLAM than the values obtained for CDV-H proteins from dog strains. By experimentally changing one amino acid (Y549H) in the CDV-H protein of one dog strain we decreased expression of specialist traits and increased expression of generalist traits, thereby confirming its functional importance. A virus titer assay demonstrated that dog strains produced higher titers in cells expressing dog SLAM than cells expressing SLAM of non-dog hosts, which suggested possible fitness benefits of specialization post-cell entry. We provide in vitro evidence for the expression of specialist and generalist traits by CDV strains, and fitness trade-offs across carnivore host environments caused by antagonistic pleiotropy. These findings extend knowledge on CDV molecular epidemiology of particular relevance to wild carnivores.",2012 Dec 11,"['Nikolin, Veljko M.', 'Osterrieder, Klaus', 'von Messling, Veronika', 'Hofer, Heribert', 'Anderson, Danielle', 'Dubovi, Edward', 'Brunner, Edgar', 'East, Marion L.']",PLoS One,,,True
72613cfcf7d9ce3ba6d87fa24e2c220a15914d73,PMC,Quantification of the Host Response Proteome after Mammalian Reovirus T1L Infection,http://dx.doi.org/10.1371/journal.pone.0051939,PMC3519901,23240068,CC BY,"All viruses are dependent upon host cells for replication. Infection can induce profound changes within cells, including apoptosis, morphological changes, and activation of signaling pathways. Many of these alterations have been analyzed by gene arrays to measure the cellular “transcriptome.” We used SILAC (stable isotope labeling by amino acids in cell culture), combined with high-throughput 2-D HPLC/mass spectrometry, to determine relative quantitative differences in host proteins at 6 and 24 hours after infecting HEK293 cells with reovirus serotype 1 Lang (T1L). 3,076 host proteins were detected at 6hpi, of which 132 and 68 proteins were significantly up or down regulated, respectively. 2,992 cellular proteins, of which 104 and 49 were up or down regulated, respectively, were identified at 24hpi. IPA and DAVID analyses indicated proteins involved in cell death, cell growth factors, oxygen transport, cell structure organization and inflammatory defense response to virus were up-regulated, whereas proteins involved in apoptosis, isomerase activity, and metabolism were down-regulated. These proteins and pathways may be suitable targets for intervention to either attenuate virus infection or enhance oncolytic potential.",2012 Dec 11,"['Berard, Alicia R.', 'Cortens, John P.', 'Krokhin, Oleg', 'Wilkins, John A.', 'Severini, Alberto', 'Coombs, Kevin M.']",PLoS One,,,True
544d61a716a23113ecb8bf04f412fbc6ba206942,PMC,Biodegradable Nanoparticle-Entrapped Vaccine Induces Cross-Protective Immune Response against a Virulent Heterologous Respiratory Viral Infection in Pigs,http://dx.doi.org/10.1371/journal.pone.0051794,PMC3519908,23240064,CC BY,"Biodegradable nanoparticle-based vaccine development research is unexplored in large animals and humans. In this study, we illustrated the efficacy of nanoparticle-entrapped UV-killed virus vaccine against an economically important respiratory viral disease of pigs called porcine reproductive and respiratory syndrome virus (PRRSV). We entrapped PLGA [poly (lactide-co-glycolides)] nanoparticles with killed PRRSV antigens (Nano-KAg) and detected its phagocytosis by pig alveolar macrophages. Single doses of Nano-KAg vaccine administered intranasally to pigs upregulated innate and PRRSV specific adaptive responses. In a virulent heterologous PRRSV challenge study, Nano-KAg vaccine significantly reduced the lung pathology and viremia, and the viral load in the lungs. Immunologically, enhanced innate and adaptive immune cell population and associated cytokines with decreased secretion of immunosuppressive mediators were observed at both mucosal sites and blood. In summary, we demonstrated the benefits of intranasal delivery of nanoparticle-based viral vaccine in eliciting cross-protective immune response in pigs, a potential large animal model.",2012 Dec 11,"['Dwivedi, Varun', 'Manickam, Cordelia', 'Binjawadagi, Basavaraj', 'Joyappa, Dechamma', 'Renukaradhya, Gourapura J.']",PLoS One,,,True
680c8cd646f4f78d97eddff21292668beba44d09,PMC,Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus,http://dx.doi.org/10.1186/1465-9921-13-43,PMC3520784,22672594,CC BY,"BACKGROUND: Influenza A virus (IAV) infection primarily targets respiratory epithelial cells and produces clinical outcomes ranging from mild upper respiratory infection to severe pneumonia. Recent studies have shown the importance of lung antioxidant defense systems against injury by IAV. Nuclear factor-erythroid 2 related factor 2 (Nrf2) activates the majority of antioxidant genes. METHODS: Alveolar type II (ATII) cells and alveolar macrophages (AM) were isolated from human lungs not suitable for transplantation and donated for medical research. In some studies ATII cells were transdifferentiated to alveolar type I-like (ATI-like) cells. Alveolar epithelial cells were infected with A/PR/8/34 (PR8) virus. We analyzed PR8 virus production, influenza A nucleoprotein levels, ROS generation and expression of antiviral genes. Immunocytofluorescence was used to determine Nrf2 translocation and western blotting to detect Nrf2, HO-1 and caspase 1 and 3 cleavage. We also analyzed ingestion of PR8 virus infected apoptotic ATII cells by AM, cytokine levels by ELISA, glutathione levels, necrosis and apoptosis by TUNEL assay. Moreover, we determined the critical importance of Nrf2 using adenovirus Nrf2 (AdNrf2) or Nrf2 siRNA to overexpress or knockdown Nrf2, respectively. RESULTS: We found that IAV induced oxidative stress, cytotoxicity and apoptosis in ATI-like and ATII cells. We also found that AM can ingest PR8 virus-induced apoptotic ATII cells (efferocytosis) but not viable cells, whereas ATII cells did not ingest these apoptotic cells. PR8 virus increased ROS production, Nrf2, HO-1, Mx1 and OAS1 expression and Nrf2 translocation to the nucleus. Nrf2 knockdown with siRNA sensitized ATI-like cells and ATII cells to injury induced by IAV and overexpression of Nrf2 with AdNrf2 protected these cells. Furthermore, Nrf2 overexpression followed by infection with PR8 virus decreased virus replication, influenza A nucleoprotein expression, antiviral response and oxidative stress. However, AdNrf2 did not increase IFN-λ1 (IL-29) levels. CONCLUSIONS: Our results indicate that IAV induces alveolar epithelial injury and that Nrf2 protects these cells from the cytopathic effects of IAV likely by increasing the expression of antioxidant genes. Identifying the pathways involved in protecting cells from injury during influenza infection may be particularly important for developing new therapeutic strategies.",2012 Jun 6,"['Kosmider, Beata', 'Messier, Elise M', 'Janssen, William J', 'Nahreini, Piruz', 'Wang, Jieru', 'Hartshorn, Kevan L', 'Mason, Robert J']",Respir Res,,,True
b0ad001bf30a7e66883a682031b9847028664e3d,PMC,Rapid production of antigen-specific monoclonal antibodies from a variety of animals,http://dx.doi.org/10.1186/1741-7007-10-80,PMC3520816,23017270,CC BY,"BACKGROUND: Although a variety of animals have been used to produce polyclonal antibodies against antigens, the production of antigen-specific monoclonal antibodies from animals remains challenging. RESULTS: We propose a simple and rapid strategy to produce monoclonal antibodies from a variety of animals. By staining lymph node cells with an antibody against immunoglobulin and a fluorescent dye specific for the endoplasmic reticulum, plasma/plasmablast cells were identified without using a series of antibodies against lineage markers. By using a fluorescently labeled antigen as a tag for a complementary cell surface immunoglobulin, antigen-specific plasma/plasmablast cells were sorted from the rest of the cell population by fluorescence-activated cell sorting. Amplification of cognate pairs of immunoglobulin heavy and light chain genes followed by DNA transfection into 293FT cells resulted in the highly efficient production of antigen-specific monoclonal antibodies from a variety of immunized animals. CONCLUSIONS: Our technology eliminates the need for both cell propagation and screening processes, offering a significant advantage over hybridoma and display strategies.",2012 Sep 28,"['Kurosawa, Nobuyuki', 'Yoshioka, Megumi', 'Fujimoto, Rika', 'Yamagishi, Fuminori', 'Isobe, Masaharu']",BMC Biol,,,True
c5f986ded9c2caf03ce509dffc7e53f93f41941c,PMC,Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants,http://dx.doi.org/10.1371/journal.pone.0051820,PMC3520906,23251633,CC BY,"The voltage-gated KCNQ1 potassium channel is expressed in cardiac tissues, and coassembly of KCNQ1 with an auxiliary KCNE1 subunit mediates a slowly activating current that accelerates the repolarization of action potential in cardiomyocytes. Mutations of KCNQ1 genes that result in reduction or loss of channel activity cause prolongation of repolarization during action potential, thereby causing long QT syndrome (LQTs). Small molecule activators of KCNQ1/KCNE1 are useful both for understanding the mechanism of the complex activity and for developing therapeutics for LQTs. In this study we report that hexachlorophene (HCP), the active component of the topical anti-infective prescription drug pHisoHex, is a KCNQ1/KCNE1 activator. HCP potently increases the current amplitude of KCNQ1/KCNE1 expressed by stabilizing the channel in an open state with an EC(50) of 4.61±1.29 μM. Further studies in cardiomyocytes showed that HCP significantly shortens the action potential duration at 1 μM. In addition, HCP is capable of rescuing the loss of function of the LQTs mutants caused by either impaired activation gating or phosphatidylinositol-4,5-bisphosphate (PIP2) binding affinity. Our results indicate HCP is a novel KCNQ1/KCNE1 activator and may be a useful tool compound for the development of LQTs therapeutics.",2012 Dec 12,"['Zheng, Yueming', 'Zhu, Xuejing', 'Zhou, Pingzheng', 'Lan, Xi', 'Xu, Haiyan', 'Li, Min', 'Gao, Zhaobing']",PLoS One,,,True
45398efb94483b10fc0547f0784cf50d6b2c7b9a,PMC,A Population Health Surveillance Theory,http://dx.doi.org/10.4178/epih/e2012007,PMC3521104,23251837,CC BY,"OBJECTIVES: Despite its extensive use, the term ""Surveillance"" often takes on various meanings in the scientific literature pertinent to public health and animal health. A critical appraisal of this literature also reveals ambiguities relating to the scope and necessary structural components underpinning the surveillance process. The authors hypothesized that these inconsistencies translate to real or perceived deficiencies in the conceptual framework of population health surveillance. This paper presents a population health surveillance theory framed upon an explicit conceptual system relative to health surveillance performed in human and animal populations. METHODS: The population health surveillance theory reflects the authors' system of thinking and was based on a creative process. RESULTS: Population health surveillance includes two broad components: one relating to the human organization (which includes expertise and the administrative program), and one relating to the system per se (which includes elements of design and method) and which can be viewed as a process. The population health surveillance process is made of five sequential interrelated steps: 1) a trigger or need, 2) problem formulation, 3) surveillance planning, 4) surveillance implementation, and 5) information communication and audit. CONCLUSIONS: The population health surveillance theory provides a systematic way of understanding, organizing and evaluating the population health surveillance process.",2012 Nov 30,"['El Allaki, Farouk', 'Bigras-Poulin, Michel', 'Michel, Pascal', 'Ravel, André']",Epidemiol Health,,,True
4dfc59a66e7a86f6a40c5fafad4c12f483ce40bc,PMC,Host-protective effect of circulating pentraxin 3 (PTX3) and complex formation with neutrophil extracellular traps,http://dx.doi.org/10.3389/fimmu.2012.00378,PMC3521240,23248627,CC BY,"Pentraxin 3 (PTX3) is a soluble pattern recognition receptor which is classified as a long-pentraxin in the pentraxin family. It is known to play an important role in innate immunity, inflammatory regulation, and female fertility. PTX3 is synthesized by specific cells, primarily in response to inflammatory signals. Among these various cells, neutrophils have a unique PTX3 production system. Neutrophils store PTX3 in neutrophil-specific granules and then the stored PTX3 is released and localizes in neutrophil extracellular traps (NETs). Although certain NET components have been identified, such as histones and anti-microbial proteins, the detailed mechanisms by which NETs localize, as well as capture and kill microbes, have not been fully elucidated. PTX3 is a candidate diagnostic marker of infection and vascular damage. In severe infectious diseases such as sepsis, the circulating PTX3 concentration increases greatly (up to 100 ng/mL, i.e., up to 100-fold of the normal level). Even though it is clearly implied that PTX3 plays a protective role in sepsis and certain other disorders, the detailed mechanisms by which it does so remain unclear. A proteomic study of PTX3 ligands in septic patients revealed that PTX3 forms a complex with certain NET component proteins. This suggests a role for PTX3 in which it facilitates the efficiency of anti-microbial protein pathogen clearance by interacting with both pathogens and anti-microbial proteins. We discuss the possible relationships between PTX3 and NET component proteins in the host protection afforded by the innate immune response. The PTX3 complex has the potential to be a highly useful diagnostic marker of sepsis and other inflammatory diseases.",2012 Dec 13,"['Daigo, Kenji', 'Hamakubo, Takao']",Front Immunol,,,True
5e3b24f55fdc84cfc263d4784c6ad6349d212866,PMC,Epimedium koreanum Nakai Water Extract Exhibits Antiviral Activity against Porcine Epidermic Diarrhea Virus In Vitro and In Vivo,http://dx.doi.org/10.1155/2012/985151,PMC3521454,23259003,CC BY,"Porcine epidemic diarrhea virus (PEDV) causes diarrhea of pigs age-independently and death of young piglets, resulting in economic loss of porcine industry. We have screened 333 natural oriental herbal medicines to search for new antiviral candidates against PEDV. We found that two herbal extracts, KIOM 198 and KIOM 124, contain significant anti-PED viral effect. KIOM 198 and KIOM 124 were identified as Epimedium koreanum Nakai and Lonicera japonica Thunberg, respectively. The further plaque and CPE inhibition assay in vitro showed that KIOM 198 has much stronger antiviral activity than KIOM 124. Additionally, KIOM 198 exhibited a similar extent of antiviral effect against other subtypes of Corona virus such as sm98 and TGE viruses. Cytotoxicity results showed that KIOM 198 is nontoxic on the cells and suggest that it can be delivered safely for therapy. Furthermore, when we orally administered KIOM 198 to piglets and then infected them with PEDV, the piglets did not show any disease symptoms like diarrhea and biopsy results showed clean intestine, whereas control pigs without KIOM 198 treatment exhibited PED-related severe symptoms. These results imply that KIOM 198 contains strong antiviral activity and has a potential to be developed as an antiviral phytomedicine to treat PEDV-related diseases in pigs.",2012 Nov 29,"['Cho, Won-Kyung', 'Kim, Hyunil', 'Choi, Yu Jeong', 'Yim, Nam-Hui', 'Yang, Hye Jin', 'Ma, Jin Yeul']",Evid Based Complement Alternat Med,,,True
0a24f22d8d49dc503c52d43dbc51459fc06fbb14,PMC,Antigenic Subversion: A Novel Mechanism of Host Immune Evasion by Ebola Virus,http://dx.doi.org/10.1371/journal.ppat.1003065,PMC3521666,23271969,CC BY,"In addition to its surface glycoprotein (GP(1,2)), Ebola virus (EBOV) directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. The generation of secreted antigens has been studied in several viruses and suggested as a mechanism of host immune evasion through absorption of antibodies and interference with antibody-mediated clearance. However such a role has not been conclusively determined for the Ebola virus sGP. In this study, we immunized mice with DNA constructs expressing GP(1,2) and/or sGP, and demonstrate that sGP can efficiently compete for anti-GP(12) antibodies, but only from mice that have been immunized by sGP. We term this phenomenon “antigenic subversion”, and propose a model whereby sGP redirects the host antibody response to focus on epitopes which it shares with membrane-bound GP(1,2), thereby allowing it to absorb anti-GP(1,2) antibodies. Unexpectedly, we found that sGP can also subvert a previously immunized host's anti-GP(1,2) response resulting in strong cross-reactivity with sGP. This finding is particularly relevant to EBOV vaccinology since it underscores the importance of eliciting robust immunity that is sufficient to rapidly clear an infection before antigenic subversion can occur. Antigenic subversion represents a novel virus escape strategy that likely helps EBOV evade host immunity, and may represent an important obstacle to EBOV vaccine design.",2012 Dec 13,"['Mohan, Gopi S.', 'Li, Wenfang', 'Ye, Ling', 'Compans, Richard W.', 'Yang, Chinglai']",PLoS Pathog,,,True
1204dc3b147d4e4d5ccc3d4aff7551d39f5fe438,PMC,Imaging Findings in Patients With H1N1 Influenza A Infection,http://dx.doi.org/10.5812/iranjradiol.4554,PMC3522360,23329946,CC BY,"BACKGROUND: Swine influenza (H1N1) is a very contagious respiratory infection and World Health Organization (WHO) has raised the alert level to phase 6 (pandemic). The study of clinical and laboratory manifestations as well as radiologic imaging findings helps in its early diagnosis. OBJECTIVES: The aim of this study was to evaluate the imaging findings of patients with documented H1N1 infection referred to our center. PATIENTS AND METHODS: Thirty-one patients (16 men) with documented H1N1 infection were included in our study. The initial radiography obtained from the patients was reviewed regarding pattern (consolidation, ground glass, nodules and reticulation), distribution (focal, multifocal, and diffuse) and the lung zones involved. Computed tomography (CT) scans were also reviewed for the same abnormalities. The patient files were studied for their possible underlying diseases. RESULTS: The mean age was 37.97 ± 13.9 years. Seventeen (54.8%) patients had co-existing condition (eight respiratory, five cardiovascular, two immunodeficiency, two cancer, four others). Twelve (38.7%) patients required intensive care unit (ICU) admission. Five (16.1%) patients died. (25.8%) had normal initial radiographs. The most common abnormality was consolidation (12/31; 38.7%) in the peripheral region (11/31; 35.5%) followed by peribronchovascular areas (10/31; 32.3%) which was most commonly observed in the lower zone. The patients admitted to the ICU were more likely to have two or more lung zones involved (P = 0.005). CONCLUSIONS: In patients with the novel swine flu infection, the most common radiographic abnormality observed was consolidation in the lower lung zones. Patients admitted to ICU were more likely to have two or more lung zones involved.",2011 Dec 25,"['Bakhshayeshkaram, Mehrdad', 'Saidi, Bahareh', 'Tabarsi, Payam', 'Zahirifard, Soheila', 'Ghofrani, Mishka']",Iran J Radiol,,,True
c47b1bf314263894ae9a5589303b7af810741267,PMC,Respiratory Viruses in Hospitalized Children with Influenza-Like Illness during the H1n1 2009 Pandemic in Sweden,http://dx.doi.org/10.1371/journal.pone.0051491,PMC3522717,23272110,CC BY,"BACKGROUND: The swine-origin influenza A(H1N1)pdm09 pandemic of 2009 had a slower spread in Europe than expected. The human rhinovirus (HRV) has been suggested to have delayed the pandemic through viral interference. The importance of co-infections over time during the pandemic and in terms of severity of the disease needs to be assessed. OBJECTIVE: The aim of this study was to investigate respiratory viruses and specifically the presence of co-infections with influenza A(H1N1)pdm09 (H1N1) in hospitalized children during the H1N1 pandemic. A secondary aim was to investigate if co-infections were associated with severity of disease. METHODS: A retrospective study was performed on 502 children with influenza-like illness admitted to inpatient care at a pediatric hospital in Stockholm, Sweden during the 6 months spanning the H1N1 pandemic in 2009. Respiratory samples were analyzed for a panel of 16 viruses by real-time polymerase chain reaction. RESULTS: One or more viruses were detected in 61.6% of the samples. Of these, 85.4% were single infections and 14.6% co-infections (2–4 viruses). The number of co-infections increased throughout the study period. H1N1 was found in 83 (16.5%) children and of these 12 (14.5%) were co-infections. HRV and H1N1 circulated to a large extent at the same time and 6.0% of the H1N1-positive children were also positive for HRV. There was no correlation between co-infections and severity of disease in children with H1N1. CONCLUSIONS: Viral co-infections were relatively common in H1N1 infected hospitalized children and need to be considered when estimating morbidity attributed to H1N1. Population-based longitudinal studies with repeated sampling are needed to improve the understanding of the importance of co-infections and viral interference.",2012 Dec 14,"['Rhedin, Samuel', 'Hamrin, Johan', 'Naucler, Pontus', 'Bennet, Rutger', 'Rotzén-Östlund, Maria', 'Färnert, Anna', 'Eriksson, Margareta']",PLoS One,,,True
05ba033423b8fcd8ca26cf0cf1611e128048f9db,PMC,Retrovirus Entry by Endocytosis and Cathepsin Proteases,http://dx.doi.org/10.1155/2012/640894,PMC3523128,23304142,CC BY,"Retroviruses include infectious agents inducing severe diseases in humans and animals. In addition, retroviruses are widely used as tools to transfer genes of interest to target cells. Understanding the entry mechanism of retroviruses contributes to developments of novel therapeutic approaches against retrovirus-induced diseases and efficient exploitation of retroviral vectors. Entry of enveloped viruses into host cell cytoplasm is achieved by fusion between the viral envelope and host cell membranes at either the cell surface or intracellular vesicles. Many animal retroviruses enter host cells through endosomes and require endosome acidification. Ecotropic murine leukemia virus entry requires cathepsin proteases activated by the endosome acidification. CD4-dependent human immunodeficiency virus (HIV) infection is thought to occur via endosomes, but endosome acidification is not necessary for the entry whereas entry of CD4-independent HIVs, which are thought to be prototypes of CD4-dependent viruses, is low pH dependent. There are several controversial results on the retroviral entry pathways. Because endocytosis and endosome acidification are complicatedly controlled by cellular mechanisms, the retrovirus entry pathways may be different in different cell lines.",2012 Dec 6,"['Kubo, Yoshinao', 'Hayashi, Hideki', 'Matsuyama, Toshifumi', 'Sato, Hironori', 'Yamamoto, Naoki']",Adv Virol,,,True
c24570f542d59b0d17450b1bd83c708f9401ca9c,PMC,Immunization with a Recombinant Vaccinia Virus That Encodes Nonstructural Proteins of the Hepatitis C Virus Suppresses Viral Protein Levels in Mouse Liver,http://dx.doi.org/10.1371/journal.pone.0051656,PMC3524174,23284733,CC BY,"Chronic hepatitis C, which is caused by infection with the hepatitis C virus (HCV), is a global health problem. Using a mouse model of hepatitis C, we examined the therapeutic effects of a recombinant vaccinia virus (rVV) that encodes an HCV protein. We generated immunocompetent mice that each expressed multiple HCV proteins via a Cre/loxP switching system and established several distinct attenuated rVV strains. The HCV core protein was expressed consistently in the liver after polyinosinic acid–polycytidylic acid injection, and these mice showed chronic hepatitis C-related pathological findings (hepatocyte abnormalities, accumulation of glycogen, steatosis), liver fibrosis, and hepatocellular carcinoma. Immunization with one rVV strain (rVV-N25), which encoded nonstructural HCV proteins, suppressed serum inflammatory cytokine levels and alleviated the symptoms of pathological chronic hepatitis C within 7 days after injection. Furthermore, HCV protein levels in liver tissue also decreased in a CD4 and CD8 T-cell-dependent manner. Consistent with these results, we showed that rVV-N25 immunization induced a robust CD8 T-cell immune response that was specific to the HCV nonstructural protein 2. We also demonstrated that the onset of chronic hepatitis in CN2-29((+/−))/MxCre((+/−)) mice was mainly attributable to inflammatory cytokines, (tumor necrosis factor) TNF-α and (interleukin) IL-6. Thus, our generated mice model should be useful for further investigation of the immunological processes associated with persistent expression of HCV proteins because these mice had not developed immune tolerance to the HCV antigen. In addition, we propose that rVV-N25 could be developed as an effective therapeutic vaccine.",2012 Dec 17,"['Sekiguchi, Satoshi', 'Kimura, Kiminori', 'Chiyo, Tomoko', 'Ohtsuki, Takahiro', 'Tobita, Yoshimi', 'Tokunaga, Yuko', 'Yasui, Fumihiko', 'Tsukiyama-Kohara, Kyoko', 'Wakita, Takaji', 'Tanaka, Toshiyuki', 'Miyasaka, Masayuki', 'Mizuno, Kyosuke', 'Hayashi, Yukiko', 'Hishima, Tsunekazu', 'Matsushima, Kouji', 'Kohara, Michinori']",PLoS One,,,True
fb3b1aad0a6c7504ba963a48906f6cbac748de77,PMC,Infectious disease aerobiology: miasma incarnate,http://dx.doi.org/10.3389/fcimb.2012.00163,PMC3525905,23267441,CC BY,,2012 Dec 19,"['Roy, Chad J.', 'Reed, Doug S.']",Front Cell Infect Microbiol,,,True
d009fdd48b7a8539c810eee5b108ca0fc6c5e6a8,PMC,"Fourth European Conference on Infections in Leukaemia (ECIL-4): Guidelines for Diagnosis and Treatment of Human Respiratory Syncytial Virus, Parainfluenza Virus, Metapneumovirus, Rhinovirus, and Coronavirus",http://dx.doi.org/10.1093/cid/cis844,PMC3526251,23024295,CC BY,"Community-acquired respiratory virus (CARV) infections have been recognized as a significant cause of morbidity and mortality in patients with leukemia and those undergoing hematopoietic stem cell transplantation (HSCT). Progression to lower respiratory tract infection with clinical and radiological signs of pneumonia and respiratory failure appears to depend on the intrinsic virulence of the specific CARV as well as factors specific to the patient, the underlying disease, and its treatment. To better define the current state of knowledge of CARVs in leukemia and HSCT patients, and to improve CARV diagnosis and management, a working group of the Fourth European Conference on Infections in Leukaemia (ECIL-4) 2011 reviewed the literature on CARVs, graded the available quality of evidence, and made recommendations according to the Infectious Diseases Society of America grading system. Owing to differences in screening, clinical presentation, and therapy for influenza and adenovirus, ECIL-4 recommendations are summarized for CARVs other than influenza and adenovirus.",2013 Jan 15,"['Hirsch, Hans H.', 'Martino, Rodrigo', 'Ward, Katherine N.', 'Boeckh, Michael', 'Einsele, Hermann', 'Ljungman, Per']",Clin Infect Dis,,,True
209fd978d66d8ffe04712de07dc7e07b779baa08,PMC,Cell-type specific requirements for thiol/disulfide exchange during HIV-1 entry and infection,http://dx.doi.org/10.1186/1742-4690-9-97,PMC3526565,23206338,CC BY,"BACKGROUND: The role of disulfide bond remodeling in HIV-1 infection is well described, but the process still remains incompletely characterized. At present, the data have been predominantly obtained using established cell lines and/or CXCR4-tropic laboratory-adapted virus strains. There is also ambiguity about which disulfide isomerases/ reductases play a major role in HIV-1 entry, as protein disulfide isomerase (PDI) and/or thioredoxin (Trx) have emerged as the two enzymes most often implicated in this process. RESULTS: We have extended our previous findings and those of others by focusing on CCR5-using HIV-1 strains and their natural targets - primary human macrophages and CD4(+) T lymphocytes. We found that the nonspecific thiol/disulfide exchange inhibitor, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), significantly reduced HIV-1 entry and infection in cell lines, human monocyte-derived macrophages (MDM), and also phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC). Subsequent studies were performed using specific anti-PDI or Trx monoclonal antibodies (mAb) in HIV-1 envelope pseudotyped and wild type (wt) virus infection systems. Although human donor-to-donor variability was observed as expected, Trx appeared to play a greater role than PDI in HIV-1 infection of MDM. In contrast, PDI, but not Trx, was predominantly involved in HIV-1 entry and infection of the CD4(+)/CCR5(+) T cell line, PM-1, and PHA-stimulated primary human T lymphocytes. Intriguingly, both PDI and Trx were present on the surface of MDM, PM-1 and PHA-stimulated CD4(+) T cells. However, considerably lower levels of Trx were detected on freshly isolated CD4(+) lymphocytes, compared to PHA-stimulated cells. CONCLUSIONS: Our findings clearly demonstrate the role of thiol/disulfide exchange in HIV-1 entry in primary T lymphocytes and MDM. They also establish a cell-type specificity regarding the involvement of particular disulfide isomerases/reductases in this process and may provide an explanation for differences among previously published studies. More importantly, from an in vivo perspective, the preferential utilization of PDI may be relevant to the HIV-1 entry and establishment of virus reservoirs in resting CD4(+) cells, while the elevated levels of Trx reported in the chronic stages of HIV-1 infection may facilitate the virus entry in macrophages and help to sustain high viremia during the decline of T lymphocytes.",2012 Dec 3,"['Stantchev, Tzanko S', 'Paciga, Mark', 'Lankford, Carla R', 'Schwartzkopff, Franziska', 'Broder, Christopher C', 'Clouse, Kathleen A']",Retrovirology,,,True
aa2d1de5f5f45ad793fffda7679200d35e971b4f,PMC,BUHO: A MATLAB Script for the Study of Stress Granules and Processing Bodies by High-Throughput Image Analysis,http://dx.doi.org/10.1371/journal.pone.0051495,PMC3527446,23284702,CC BY,"The spontaneous and reversible formation of foci and filaments that contain proteins involved in different metabolic processes is common in both the nucleus and the cytoplasm. Stress granules (SGs) and processing bodies (PBs) belong to a novel family of cellular structures collectively known as mRNA silencing foci that harbour repressed mRNAs and their associated proteins. SGs and PBs are highly dynamic and they form upon stress and dissolve thus releasing the repressed mRNAs according to changes in cell physiology. In addition, aggregates containing abnormal proteins are frequent in neurodegenerative disorders. In spite of the growing relevance of these supramolecular aggregates to diverse cellular functions a reliable automated tool for their systematic analysis is lacking. Here we report a MATLAB Script termed BUHO for the high-throughput image analysis of cellular foci. We used BUHO to assess the number, size and distribution of distinct objects with minimal deviation from manually obtained parameters. BUHO successfully addressed the induction of both SGs and PBs in mammalian and insect cells exposed to different stress stimuli. We also used BUHO to assess the dynamics of specific mRNA-silencing foci termed Smaug 1 foci (S-foci) in primary neurons upon synaptic stimulation. Finally, we used BUHO to analyze the role of candidate genes on SG formation in an RNAi-based experiment. We found that FAK56D, GCN2 and PP1 govern SG formation. The role of PP1 is conserved in mammalian cells as judged by the effect of the PP1 inhibitor salubrinal, and involves dephosphorylation of the translation factor eIF2α. All these experiments were analyzed manually and by BUHO and the results differed in less than 5% of the average value. The automated analysis by this user-friendly method will allow high-throughput image processing in short times by providing a robust, flexible and reliable alternative to the laborious and sometimes unfeasible visual scrutiny.",2012 Dec 20,"['Perez-Pepe, Marcelo', 'Slomiansky, Victoria', 'Loschi, Mariela', 'Luchelli, Luciana', 'Neme, Maximiliano', 'Thomas, María Gabriela', 'Boccaccio, Graciela Lidia']",PLoS One,,,True
b0889b0058183e21ed81e8b41414fd4cc450ce84,PMC,"Adjuvant Activity of Sargassum pallidum Polysaccharides against Combined Newcastle Disease, Infectious Bronchitis and Avian Influenza Inactivated Vaccines",http://dx.doi.org/10.3390/md10122648,PMC3528116,23342387,CC BY,"This study evaluates the effects of Sargassum pallidum polysaccharides (SPP) on the immune responses in a chicken model. The adjuvanticity of Sargassum pallidum polysaccharides in Newcastle disease (ND), infectious bronchitis (IB) and avian influenza (AI) was investigated by examining the antibody titers and lymphocyte proliferation following immunization in chickens. The chickens were administrated combined ND, IB and AI inactivated vaccines containing SPP at 10, 30 and 50 mg/mL, using an oil adjuvant vaccine as a control. The ND, IB and AI antibody titers and the lymphocyte proliferation were enhanced at 30 mg/mL SPP. In conclusion, an appropriate dose of SPP may be a safe and efficacious immune stimulator candidate that is suitable for vaccines to produce early and persistent prophylaxis.",2012 Nov 22,"['Li, Li-Jie', 'Li, Ming-Yi', 'Li, Yan-Tuan', 'Feng, Jing-Jing', 'Hao, Feng-Qiang', 'Zhang, Lun']",Mar Drugs,,,True
11588188717735eb36e684003283dbe2d9832286,PMC,"Host Cell Factors in Filovirus Entry: Novel Players, New Insights",http://dx.doi.org/10.3390/v4123336,PMC3528269,23342362,CC BY,"Filoviruses cause severe hemorrhagic fever in humans with high case-fatality rates. The cellular factors exploited by filoviruses for their spread constitute potential targets for intervention, but are incompletely defined. The viral glycoprotein (GP) mediates filovirus entry into host cells. Recent studies revealed important insights into the host cell molecules engaged by GP for cellular entry. The binding of GP to cellular lectins was found to concentrate virions onto susceptible cells and might contribute to the early and sustained infection of macrophages and dendritic cells, important viral targets. Tyrosine kinase receptors were shown to promote macropinocytic uptake of filoviruses into a subset of susceptible cells without binding to GP, while interactions between GP and human T cell Ig mucin 1 (TIM-1) might contribute to filovirus infection of mucosal epithelial cells. Moreover, GP engagement of the cholesterol transporter Niemann-Pick C1 was demonstrated to be essential for GP-mediated fusion of the viral envelope with a host cell membrane. Finally, mutagenic and structural analyses defined GP domains which interact with these host cell factors. Here, we will review the recent progress in elucidating the molecular interactions underlying filovirus entry and discuss their implications for our understanding of the viral cell tropism.",2012 Nov 26,"['Hofmann-Winkler, Heike', 'Kaup, Franziska', 'Pöhlmann, Stefan']",Viruses,,,True
2fa46e22a7460345c3a4aed5aca12df56667cb56,PMC,Innate Immunity to H5N1 Influenza Viruses in Humans,http://dx.doi.org/10.3390/v4123363,PMC3528270,23342363,CC BY,"Avian influenza virus infections in the human population are rare due to their inefficient direct human-to-human transmission. However, when humans are infected, a strong inflammatory response is usually induced, characterized by elevated levels of cytokines and chemokines in serum, believed to be important in the severe pathogenesis that develops in a high proportion of these patients. Extensive research has been performed to understand the molecular viral mechanisms involved in the H5N1 pathogenesis in humans, providing interesting insights about the virus-host interaction and the regulation of the innate immune response by these highly pathogenic viruses. In this review we summarize and discuss the most important findings in this field, focusing mainly on H5N1 virulence factors and their impact on the modulation of the innate immunity in humans.",2012 Nov 26,"['Ramos, Irene', 'Fernandez-Sesma, Ana']",Viruses,,,True
324224a860eb73492e4207926e5ea62cd1a910d9,PMC,Involvement of Autophagy in Coronavirus Replication,http://dx.doi.org/10.3390/v4123440,PMC3528273,23202545,CC BY,"Coronaviruses are single stranded, positive sense RNA viruses, which induce the rearrangement of cellular membranes upon infection of a host cell. This provides the virus with a platform for the assembly of viral replication complexes, improving efficiency of RNA synthesis. The membranes observed in coronavirus infected cells include double membrane vesicles. By nature of their double membrane, these vesicles resemble cellular autophagosomes, generated during the cellular autophagy pathway. In addition, coronavirus infection has been demonstrated to induce autophagy. Here we review current knowledge of coronavirus induced membrane rearrangements and the involvement of autophagy or autophagy protein microtubule associated protein 1B light chain 3 (LC3) in coronavirus replication.",2012 Nov 30,"['Maier, Helena J.', 'Britton, Paul']",Viruses,,,True
5e2dc7663e6a6b53d6b8f37f5ccd4e6dc0c71a57,PMC,"Epidemiology, Molecular Epidemiology and Evolution of Bovine Respiratory Syncytial Virus",http://dx.doi.org/10.3390/v4123452,PMC3528274,23202546,CC BY,"The bovine respiratory syncytial virus (BRSV) is an enveloped, negative sense, single-stranded RNA virus belonging to the pneumovirus genus within the family Paramyxoviridae. BRSV has been recognized as a major cause of respiratory disease in young calves since the early 1970s. The analysis of BRSV infection was originally hampered by its characteristic lability and poor growth in vitro. However, the advent of numerous immunological and molecular methods has facilitated the study of BRSV enormously. The knowledge gained from these studies has also provided the opportunity to develop safe, stable, attenuated virus vaccine candidates. Nonetheless, many aspects of the epidemiology, molecular epidemiology and evolution of the virus are still not fully understood. The natural course of infection is rather complex and further complicates diagnosis, treatment and the implementation of preventive measures aimed to control the disease. Therefore, understanding the mechanisms by which BRSV is able to establish infection is needed to prevent viral and disease spread. This review discusses important information regarding the epidemiology and molecular epidemiology of BRSV worldwide, and it highlights the importance of viral evolution in virus transmission.",2012 Nov 30,"['Sarmiento-Silva, Rosa Elena', 'Nakamura-Lopez, Yuko', 'Vaughan, Gilberto']",Viruses,,,True
5136621ef7ae0c8d8b2dd396e432bedceb3f0331,PMC,Identification and Characterization of a Novel Alpaca Respiratory Coronavirus Most Closely Related to the Human Coronavirus 229E,http://dx.doi.org/10.3390/v4123689,PMC3528286,23235471,CC BY,"In 2007, a novel coronavirus associated with an acute respiratory disease in alpacas (Alpaca Coronavirus, ACoV) was isolated. Full-length genomic sequencing of the ACoV demonstrated the genome to be consistent with other Alphacoronaviruses. A putative additional open-reading frame was identified between the nucleocapsid gene and 3'UTR. The ACoV was genetically most similar to the common human coronavirus (HCoV) 229E with 92.2% nucleotide identity over the entire genome. A comparison of spike gene sequences from ACoV and from HCoV-229E isolates recovered over a span of five decades showed the ACoV to be most similar to viruses isolated in the 1960’s to early 1980’s. The true origin of the ACoV is unknown, however a common ancestor between the ACoV and HCoV-229E appears to have existed prior to the 1960’s, suggesting virus transmission, either as a zoonosis or anthroponosis, has occurred between alpacas and humans.",2012 Dec 12,"['Crossley, Beate M.', 'Mock, Richard E.', 'Callison, Scott A.', 'Hietala, Sharon K.']",Viruses,,,True
1be8f67d3b7d2730be96799adfc38746474b0a3b,PMC,The effect of infection order of porcine circovirus type 2 and porcine reproductive and respiratory syndrome virus on dually infected swine alveolar macrophages,http://dx.doi.org/10.1186/1746-6148-8-174,PMC3528418,23009687,CC BY,"BACKGROUND: Concurrent infection with porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) is known as one of the major causes for porcine respiratory disease complex (PRDC). Dual infection with PCV2 and PRRSV is consistently to have more severe clinical presentations and pulmonary lesions than infection with PCV2 alone or PRRSV alone. However, it is not known if dual infections with PCV2 and PRRSV in different infection order may lead to different clinical symptoms in the host. To mimic the possible field conditions, swine alveolar macrophages (AMs) were inoculated with PCV2 and PRRSV in vitro simultaneously or with one virus 18 h earlier than the other. The cell viability, cytopathic effects, antigen-containing rates, phagocytotic and microbial killing capabilities, cytokine profiles (IL-8, TNF-α, and IFN-α) and FasL transcripts were determined, analyzed, and compared to prove the hypothesis. RESULTS: A marked reduction in PRRSV antigen-containing rate, cytopathic effect, and TNF-α expression level was revealed in AMs inoculated with PCV2 and PRRSV simultaneously and in AMs inoculated with PCV2 first then PRRSV 18 h later, but not in AMs inoculated with PRRSV first then PCV2 18 h later. Transient decrease in phagocytosis but constant reduction in microbicidal capability in AMs in the group inoculated with PCV2 alone and constant decrease in phagocytosis and microbicidal capability in AMs in all PRRSV-inoculated groups were noted. The levels of IL-8, TNF-α, IFN-α, and FasL transcripts in AMs in all groups with dual inoculation of PCV2 and PRRSV were significantly increased regardless of the infection orders as compared with infection by PCV2 alone or PRRSV alone. CONCLUSIONS: Swine AMs infected with PCV2 first then PRRSV later or infected with PCV2 and PRRSV simultaneously displayed marked reduction in PRRSV antigen-containing rate, cytopathic effect, and TNF-α expression level. The different inoculation orders of PCV2 and PRRSV in AMs leading to different results in viral antigen positivity, cytopathology, and cytokine profile may explain, at least partially, the underlying mechanism of the enhanced pulmonary lesions in PRDC exerted by dual infection with PCV2 and PRRSV and the variable clinical manifestations of PRDC-affected pigs in the field.",2012 Sep 25,"['Tsai, Yi-Chieh', 'Chang, Hui-Wen', 'Jeng, Chian-Ren', 'Lin, Tsang-Long', 'Lin, Chun-Ming', 'Wan, Cho-Hua', 'Pang, Victor Fei']",BMC Vet Res,,,True
633715b2acfa849d613285b7a01531072c2b3422,PMC,Analysis of the humoral immune responses among cynomolgus macaque naturally infected with Reston virus during the 1996 outbreak in the Philippines,http://dx.doi.org/10.1186/1746-6148-8-189,PMC3528628,23057674,CC BY,"BACKGROUND: Ebolaviruses induce lethal viral hemorrhagic fevers (VHFs) in humans and non-human primates, with the exceptions of Reston virus (RESTV), which is not pathogenic for humans. In human VHF cases, extensive analyses of the humoral immune responses in survivors and non-survivors have shown that the IgG responses to nucleoprotein (NP) and other viral proteins are associated with asymptomatic and survival outcomes, and that the neutralizing antibody responses targeting ebolaviruses glycoprotein (GP(1,2)) are the major indicator of protective immunity. On the other hand, the immune responses in non-human primates, especially naturally infected ones, have not yet been elucidated in detail, and the significance of the antibody responses against NP and GP(1,2) in RESTV-infected cynomolgus macaques is still unclear. In this study, we analyzed the humoral immune responses of cynomolgus macaque by using serum specimens obtained from the RESTV epizootic in 1996 in the Philippines to expand our knowledge on the immune responses in naturally RESTV-infected non-human primates. RESULTS: The antibody responses were analyzed using IgG-ELISA, an indirect immunofluorescent antibody assay (IFA), and a pseudotyped VSV-based neutralizing (NT) assay. Antigen-capture (Ag)-ELISA was also performed to detect viral antigens in the serum specimens. We found that the anti-GP(1,2) responses, but not the anti-NP responses, closely were correlated with the neutralization responses, as well as the clearance of viremia in the sera of the RESTV-infected cynomolgus macaques. Additionally, by analyzing the cytokine/chemokine concentrations of these serum specimens, we found high concentrations of proinflammatory cytokines/chemokines, such as IFNγ, IL8, IL-12, and MIP1α, in the convalescent phase sera. CONCLUSIONS: These results imply that both the antibody response to GP(1,2) and the proinflammatory innate responses play significant roles in the recovery from RESTV infection in cynomolgus macaques.",2012 Oct 11,"['Taniguchi, Satoshi', 'Sayama, Yusuke', 'Nagata, Noriyo', 'Ikegami, Tetsuro', 'Miranda, Mary E', 'Watanabe, Shumpei', 'Iizuka, Itoe', 'Fukushi, Shuetsu', 'Mizutani, Tetsuya', 'Ishii, Yoshiyuki', 'Saijo, Masayuki', 'Akashi, Hiroomi', 'Yoshikawa, Yasuhiro', 'Kyuwa, Shigeru', 'Morikawa, Shigeru']",BMC Vet Res,,,True
2c1d22afddf9c0d5ea6ae358aab7171b06fbdf0f,PMC,Secondary Syphilis with Pleural Effusion: Case Report and Literature Review,http://dx.doi.org/10.1155/2012/409896,PMC3530861,23304580,CC BY,"Here we present a case of a 38-year-old Indian man with a history of extramarital relationships who presented with pleurisy, skin rash, and radiological findings of pleural effusion. After thorough investigation of the etiology of his acute illness, he was found to be positive for syphilis. Review of literature revealed a small number of case reports of pleural effusion as a manifestation of secondary syphilis. The review of criteria proposed in the literature was utilized to diagnose this patient as a case of pulmonary syphilis.",2012 Dec 13,"['Elzouki, Abdel-Naser', 'Al-Kawaaz, Mustafa', 'Tafesh, Zaid']",Case Rep Infect Dis,,,True
69ef51ebe3e2ce0b8d6fc292b06b293ba2942bd7,PMC,Phylodynamic Inference and Model Assessment with Approximate Bayesian Computation: Influenza as a Case Study,http://dx.doi.org/10.1371/journal.pcbi.1002835,PMC3531293,23300420,CC BY,"A key priority in infectious disease research is to understand the ecological and evolutionary drivers of viral diseases from data on disease incidence as well as viral genetic and antigenic variation. We propose using a simulation-based, Bayesian method known as Approximate Bayesian Computation (ABC) to fit and assess phylodynamic models that simulate pathogen evolution and ecology against summaries of these data. We illustrate the versatility of the method by analyzing two spatial models describing the phylodynamics of interpandemic human influenza virus subtype A(H3N2). The first model captures antigenic drift phenomenologically with continuously waning immunity, and the second epochal evolution model describes the replacement of major, relatively long-lived antigenic clusters. Combining features of long-term surveillance data from the Netherlands with features of influenza A (H3N2) hemagglutinin gene sequences sampled in northern Europe, key phylodynamic parameters can be estimated with ABC. Goodness-of-fit analyses reveal that the irregularity in interannual incidence and H3N2's ladder-like hemagglutinin phylogeny are quantitatively only reproduced under the epochal evolution model within a spatial context. However, the concomitant incidence dynamics result in a very large reproductive number and are not consistent with empirical estimates of H3N2's population level attack rate. These results demonstrate that the interactions between the evolutionary and ecological processes impose multiple quantitative constraints on the phylodynamic trajectories of influenza A(H3N2), so that sequence and surveillance data can be used synergistically. ABC, one of several data synthesis approaches, can easily interface a broad class of phylodynamic models with various types of data but requires careful calibration of the summaries and tolerance parameters.",2012 Dec 27,"['Ratmann, Oliver', 'Donker, Gé', 'Meijer, Adam', 'Fraser, Christophe', 'Koelle, Katia']",PLoS Comput Biol,,,True
18f11e6900b1a76027c33f5e61ae9cb66d7d2370,PMC,Phylodynamic Inference and Model Assessment with Approximate Bayesian Computation: Influenza as a Case Study,http://dx.doi.org/10.1371/journal.pcbi.1002835,PMC3531293,23300420,CC BY,"A key priority in infectious disease research is to understand the ecological and evolutionary drivers of viral diseases from data on disease incidence as well as viral genetic and antigenic variation. We propose using a simulation-based, Bayesian method known as Approximate Bayesian Computation (ABC) to fit and assess phylodynamic models that simulate pathogen evolution and ecology against summaries of these data. We illustrate the versatility of the method by analyzing two spatial models describing the phylodynamics of interpandemic human influenza virus subtype A(H3N2). The first model captures antigenic drift phenomenologically with continuously waning immunity, and the second epochal evolution model describes the replacement of major, relatively long-lived antigenic clusters. Combining features of long-term surveillance data from the Netherlands with features of influenza A (H3N2) hemagglutinin gene sequences sampled in northern Europe, key phylodynamic parameters can be estimated with ABC. Goodness-of-fit analyses reveal that the irregularity in interannual incidence and H3N2's ladder-like hemagglutinin phylogeny are quantitatively only reproduced under the epochal evolution model within a spatial context. However, the concomitant incidence dynamics result in a very large reproductive number and are not consistent with empirical estimates of H3N2's population level attack rate. These results demonstrate that the interactions between the evolutionary and ecological processes impose multiple quantitative constraints on the phylodynamic trajectories of influenza A(H3N2), so that sequence and surveillance data can be used synergistically. ABC, one of several data synthesis approaches, can easily interface a broad class of phylodynamic models with various types of data but requires careful calibration of the summaries and tolerance parameters.",2012 Dec 27,"['Ratmann, Oliver', 'Donker, Gé', 'Meijer, Adam', 'Fraser, Christophe', 'Koelle, Katia']",PLoS Comput Biol,,,True
599be9828fd5c11926e88c8474f37f67f1fe4ebc,PMC,Virus-induced ER stress and the unfolded protein response,http://dx.doi.org/10.3389/fpls.2012.00293,PMC3531707,23293645,CC BY,"The accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER) results in ER stress that triggers cytoprotective signaling pathways, termed the unfolded protein response (UPR), to restore and maintain homeostasis in the ER or to induce apoptosis if ER stress remains unmitigated. The UPR signaling network encompasses three core elements, i.e., PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring protein-1 (IRE1). Activation of these three branch pathways of the UPR leads to the translation arrest and degradation of misfolded proteins, the expression of ER molecular chaperones, and the expansion of the ER membrane to decrease the load of proteins and increase the protein-folding capacity in the ER. Recently, the essential roles of the UPR have been implicated in a number of mammalian diseases, particularly viral diseases. In virus-infected cells, the cellular translation machinery is hijacked by the infecting virus to produce large amounts of viral proteins, which inevitably perturbs ER homeostasis and causes ER stress. This review summarizes current knowledge about the UPR signaling pathways, highlights two identified UPR pathways in plants, and discuss progress in elucidating the UPR in virus-infected cells and its functional roles in viral infection.",2012 Dec 28,"['Zhang, Lingrui', 'Wang, Aiming']",Front Plant Sci,,,True
a4ffcadecc4b60c30df8f699c480724523272e62,PMC,First Discovery and Stucture-Activity Relationship Study of Phenanthroquinolizidines as Novel Antiviral Agents against Tobacco Mosaic Virus (TMV),http://dx.doi.org/10.1371/journal.pone.0052933,PMC3532156,23285230,CC BY,"A series of phenanthroquinolizidine alkaloids 1–24 were prepared and first evaluated for their antiviral activity against tobacco mosaic virus (TMV). The bioassay results showed that most of these compounds exhibited good to excellent in vivo anti-TMV activity, of which compounds 1, 2, 15 and 16 displayed significantly higher activity than (R)-antofine and commercial Ningnanmycin at the same test condition. The substituents on the phenanthrene moiety play an important role for maintaining high in vivo antiviral activity. The introduction of 6-hydroxyl, which is proposed to interact with TMV RNA, did increased anti-TMV activity. The 14aR-configuration was confirmed to be the preferred antiviral configuration for phenanthroquinolizidine alkaloids. Introduction of hydroxy group at 15-position of phenanthroquinolizidine alkaloids increased activity for S-configuration but decreased activity for R-configuration. Present study provides fundamental support for development and optimization of phenanthroquinolizidine alkaloids as potential inhibitors of plant virus.",2012 Dec 28,"['Wang, Ziwen', 'Feng, Anzheng', 'Cui, Mingbo', 'Liu, Yuxiu', 'Wang, Lizhong', 'Wang, Qingmin']",PLoS One,,,True
12fc7df6445be6360090621b75df383ce86772af,PMC,Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models,http://dx.doi.org/10.1186/1472-6882-12-237,PMC3533872,23190501,CC BY,"BACKGROUND: Cinnamon bark is one of the most popular herbal ingredients in traditional oriental medicine and possesses diverse pharmacological activities including anti-bacterial, anti-viral, and anti-cancer properties. The goal of this study is to investigate the in vivo and in vitro inhibitory effect of cinnamon water extract (CWE) on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and its underlying intracellular mechanisms. METHODS: CWE was orally administrated to mice for 6 days prior to intraperitoneal injection of LPS. Serum levels of TNF-α and interleukin (IL)-6 were determined 1 hour after LPS stimulation. Peritoneal macrophages from thioglycollate-injected mice were isolated and assayed for viability, cytokine expression and signaling molecules upon LPS stimulation. CWE was further fractioned according to molecular size, and the levels of total polyphenols and biological activities of each fraction were measured. RESULTS: The oral administration of CWE to mice significantly decreased the serum levels of TNF-α and IL-6. CWE treatment in vitro decreased the mRNA expression of TNF-α. CWE blocked the LPS-induced degradation of IκBα as well as the activation of JNK, p38 and ERK1/2. Furthermore, size-based fractionation of CWE showed that the observed inhibitory effect of CWE in vitro occurred in the fraction containing the highest level of total polyphenols. CONCLUSIONS: Treatment with CWE decreased LPS-induced TNF-α in serum. In vitro inhibition of TNF-α gene by CWE may occur via the modulation of IκBα degradation and JNK, p38, and ERK1/2 activation. Our results also indicate that the observed anti-inflammatory action of CWE may originate from the presence of polyphenols.",2012 Nov 28,"['Hong, Joung-Woo', 'Yang, Ga-Eun', 'Kim, Yoon Bum', 'Eom, Seok Hyun', 'Lew, Jae-Hwan', 'Kang, Hee']",BMC Complement Altern Med,,,True
e11512bdc7871914c25d4ba5b098979d34123c34,PMC,Effectiveness of Integrated HIV Prevention Interventions among Chinese Men Who Have Sex with Men: Evaluation of a 16-City Public Health Program,http://dx.doi.org/10.1371/journal.pone.0050873,PMC3534092,23300528,CC BY,"To examine the impacts of a multi-city HIV prevention public health program (China Global Fund Round 5 Project) on condom use and HIV infection, we analyzed four yearly cross-sectional surveys from 2006 through 2009 among 20,843 men who have sex with men (MSM) in 16 Chinese cities. Self-reported condom use at last sex with a male partner increased from 58% in 2006 to 81% in 2009 (trend test, P<0.001). HIV prevalence increased from 2.3% in 2006 to 5.3% in 2009 (P<0.001). Multivariable logistic regression analysis showed that self-reported receipt of interventions was an independent predictor of increased condom use at last sex with a male partner over time (adjusted odds ratio [aOR], 1.63 in 2006 to 2.33 in 2009; P<0.001), and lower HIV prevalence (aOR, 1.08 in 2006 to 0.45 in 2009; P<0.001). HIV prevalence increased from 2006–2009 for participants with no self-reported receipt of interventions (2.1% in 2006 to 10.3% in 2009) and less so for those with interventions (2.4% to 4.7%). This Chinese public health program had positive impacts on both behaviors and disease rate among MSM population. Escalation of the coverage and intensity of effective interventions is needed for further increasing condom use and for reversing the rising trend of HIV epidemic.",2012 Dec 31,"['Ye, Shaodong', 'Xiao, Yan', 'Jin, Canrui', 'Cassell, Holly', 'Blevins, Meridith', 'Sun, Jiangping', 'Vermund, Sten H.', 'Qian, Han-Zhu']",PLoS One,,,True
a94e4109b44346c490243c71fd533cd1a9fd047c,PMC,Anti-HBV efficacy of combined siRNAs targeting viral gene and heat shock cognate 70,http://dx.doi.org/10.1186/1743-422X-9-275,PMC3534549,23158906,CC BY,"BACKGROUND: Hepatitis B virus (HBV) infection is a major health concern with more than two billion individuals currently infected worldwide. Because of the limited effectiveness of existing vaccines and drugs, development of novel antiviral strategies is urgently needed. Heat stress cognate 70 (Hsc70) is an ATP-binding protein of the heat stress protein 70 family. Hsc70 has been found to be required for HBV DNA replication. Here we report, for the first time, that combined siRNAs targeting viral gene and siHsc70 are highly effective in suppressing ongoing HBV expression and replication. METHODS: We constructed two plasmids (S1 and S2) expressing short hairpin RNAs (shRNAs) targeting surface open reading frame of HBV(HBVS) and one plasmid expressing shRNA targeting Hsc70 (siHsc70), and we used the EGFP-specific siRNA plasmid (siEGFP) as we had previously described. First, we evaluated the gene-silencing efficacy of both shRNAs using an enhanced green fluorescent protein (EGFP) reporter system and flow cytometry in HEK293 and T98G cells. Then, the antiviral potencies of HBV-specific siRNA (siHBV) in combination with siHsc70 in HepG2.2.15 cells were investigated. Moreover, type I IFN and TNF-α induction were measured by quantitative real-time PCR and ELISA. RESULTS: Cotransfection of either S1 or S2 with an EGFP plasmid produced an 80%–90% reduction in EGFP signal relative to the control. This combinational RNAi effectively and specifically inhibited HBV protein, mRNA and HBV DNA, resulting in up to a 3.36 log(10) reduction in HBV load in the HepG2.2.15 cell culture supernatants. The combined siRNAs were more potent than siHBV or siHsc70 used separately, and this approach can enhance potency in suppressing ongoing viral gene expression and replication in HepG2.2.15 cells while forestalling escape by mutant HBV. The antiviral synergy of siHBV used in combination with siHsc70 produced no cytotoxicity and induced no production of IFN-α, IFN-β and TNF-α in transfected cells. CONCLUSIONS: Our combinational RNAi was sequence-specific, effective against wild-type and mutant drug-resistant HBV strains, without triggering interferon response or producing any side effects. These findings indicate that combinational RNAi has tremendous promise for developing innovative therapy against viral infection.",2012 Nov 16,"['Bian, Zhongqi', 'Xiao, An', 'Cao, Mingmei', 'Liu, Mingqiu', 'Liu, Shuang', 'Jiao, Ye', 'Yan, Weiyao', 'Qi, Zhongtian', 'Zheng, Zhaoxin']",Virol J,,,True
009002e8a66b8c1df088cf04069629fd76b13bb9,PMC,Epidemiological Characteristics of Imported Influenza A (H1N1) Cases during the 2009 Pandemic in Korea,http://dx.doi.org/10.4178/epih/e2012009,PMC3535160,23316418,CC BY,"OBJECTIVES: Quarantine measure for prevention of epidemic disease and further evaluations of their efficiency are possible only by elaborating analyses of imported cases. The purpose of this study was to analyze descriptive epidemiological characteristics of pandemic influenza A (H1N1) cases imported to Korea. METHODS: We collected two sets of data. The first set, comprised daily reported cases of H1N1 obtained from local cities in accordance with government policy about mandatory reporting of all H1N1 cases during May 1 to August 19, 2009. The second set, including 372 confirmed imported H1N1 cases, identified from 13 National Quarantine Stations in the Korea Centers for Disease Control and Prevention from May 24 to December 31, 2009. However, given the lack of information on the nature of the imported H1N1 cases from the two data sets during the over lapping period from May 24 to August 19, we express the number of imported cases as a range for this period. RESULTS: We estimated that the number of imported H1N1 cases from May 1 to August 19, 2009, was between 1,098 and 1,291 and the total number of cases was 2,409 to 2,580. We found the number of imported cases was beginning to diminish as of August. A analysis of the second data set showed that the distribution of sex was similar (males 50.7%, females 49.3%) and the age distribution from 20 to 59 was 61.5% and that of 60 and over was 0.8% of the 372 cases. We identified 25 countries where people infected with H1N1 traveled and 67.5% were in Asia. But the proportion of cases (/1,000) by region shows Oceania (0.199), South America (0.118), Southeast Asia (0.071), North America (0.049), Europe (0.035), and Northeast Asia (0.016) in that order. The order of H1N1 peaking was the Southern Hemisphere, Tropics, and the Nothern Hemisphere. CONCLUSIONS: This study provided information that could make possible the evaluation of the government quarantine measure for stopping imported disease from causing community-acquired spread in the future.",2012 Dec 31,"['Choi, Jun Kil', 'Lee, Sang Won', 'Choi, Bo Youl']",Epidemiol Health,,,True
725b175750813a29f16faee9a389ed706eba5ae4,PMC,The 19 kDa Mycobacterium tuberculosis Lipoprotein (LpqH) Induces Macrophage Apoptosis through Extrinsic and Intrinsic Pathways: A Role for the Mitochondrial Apoptosis-Inducing Factor,http://dx.doi.org/10.1155/2012/950503,PMC3536062,23316255,CC BY,"We describe the association of caspase-dependent and caspase-independent mechanisms in macrophage apoptosis induced by LpqH, a 19 kDa Mycobacterium tuberculosis lipoprotein. LpqH triggered TLR2 activation, with upregulation of death receptors and ligands, which was followed by a death receptor signaling cascade with activation of initiator caspase 8 and executioner caspase 3. In this caspase-mediated phase, mitochondrial factors were involved in loss of mitochondrial transmembrane potential (ΔΨm), release of cytochrome c, and caspase 9 activation. Interestingly, a caspase-independent pathway was also identified; by immunoblot, the mitochondrial apoptosis inducing factor (AIF) was demonstrated in nuclei and cytosol of LpqH-treated macrophages. Confocal microscopy revealed translocation of AIF to the nuclei of the majority of apoptotic cells. These findings emphasize the complex and redundant nature of the macrophage death response to mycobacteria.",2012 Dec 19,"['Sánchez, Alejandro', 'Espinosa, Patricia', 'García, Teresa', 'Mancilla, Raúl']",Clin Dev Immunol,,,True
ef64fa65c77a221698f7cf13acdcf801ed2d554b,PMC,A novel strategy for efficient production of anti-V3 human scFvs against HIV-1 clade C,http://dx.doi.org/10.1186/1472-6750-12-87,PMC3536577,23153214,CC BY,"BACKGROUND: Production of human monoclonal antibodies that exhibit broadly neutralizing activity is needed for preventing HIV-1 infection, however only a few such antibodies have been generated till date. Isolation of antibodies by the hybridoma technology is a cumbersome process with fewer yields. Further, the loss of unstable or slowly growing clones which may have unique binding specificities often occurs during cloning and propagation and the strongly positive clones are often lost. This has been avoided by the process described in this paper, wherein, by combining the strategy of EBV transformation and recombinant DNA technology, we constructed human single chain variable fragments (scFvs) against the third variable region (V3) of the clade C HIV-1 envelope. RESULTS: An antigen specific phage library of 7000 clones was constructed from the enriched V3- positive antibody secreting EBV transformed cells. By ligation of the digested scFv DNA into phagemid vector and bio panning against the HIV-1 consensus C and B V3 peptides followed by random selection of 40 clones, we identified 15 clones that showed V3 reactivity in phage ELISA. DNA fingerprinting analysis and sequencing showed that 13 out of the 15 clones were distinct. Expression of the positive clones was tested by SDS-PAGE and Western blot. All the 13 anti-V3 scFvs showed cross-reactivity against both the clade C and B V3 peptides and did not show any reactivity against other unrelated peptides in ELISA. Preliminary neutralization assays indicated varying degrees of neutralization of clade C and B viruses. EBV transformation, followed by antigen selection of lines to identify specific binders, enabled the selection of phage from un-cloned lines for scFv generation, thus avoiding the problems of hybridoma technology. Moreover, as the clones were pretested for antigen binding, a comparatively small library sufficed for the selection of a considerable number of unique antigen binding phage. After selection, the phage clones were propagated in a clonal manner. CONCLUSIONS: This strategy can be efficiently used and is cost effective for the generation of diverse recombinant antibodies. This is the first study to generate anti-V3 scFvs against HIV-1 Clade C.",2012 Nov 15,"['Kumar, Rajesh', 'Andrabi, Raiees', 'Tiwari, Ashutosh', 'Prakash, Somi Sankaran', 'Wig, Naveet', 'Dutta, Durgashree', 'Sankhyan, Anurag', 'Khan, Lubina', 'Sinha, Subrata', 'Luthra, Kalpana']",BMC Biotechnol,,,True
bc5761e9d769b9fb1e723e1932ee3c5d4e21bd0a,PMC,Stimulation with a class A CpG oligonucleotide enhances resistance to infection with feline viruses from five different families,http://dx.doi.org/10.1186/1297-9716-43-60,PMC3537549,22906110,CC BY,"Domestic cats are commonly affected by viral pathogens that induce lengthy infections with fatal outcomes. Prevention of viral propagation is of primordial importance in shelters and catteries, where cats from different backgrounds have narrow contacts. Oligonucleotides (ODN) containing cytosine-phosphate-guanosine motifs of class A (CpG-A) are highly potent synthetic inducers of innate antiviral mechanisms. The aim of this study was to test their ability to modulate innate immune responses and prevent viral replication as stand-alone agents in the domestic cat. CpG-A stimulation of feline peripheral blood mononuclear cells (PBMCs) enhanced their proliferation, increased the presence of co-stimulatory molecules on their surface and influenced their gene expression profiles in an antiviral orientation. Incubation of the supernatants of CpG-A stimulated PBMCs with feline cell lines of epithelial and fibroblastic origin induced expression of the antiviral myxovirus resistance (Mx) gene in these target cells, which also showed enhanced resistance to feline viruses from five distinct families, namely Coronaviridae, Herpesviridae, Caliciviridae, Parvoviridae, and Retroviridae. Most importantly, subcutaneous administration of CpG-A in domestic cats systemically increased the expression of Mx, reaching maximal levels within 24 h. Plasma from treated cats could furthermore inhibit viral replication in vitro. Altogether, our data highlight the promising potential of CpG-A to induce a preventive antiviral state in the cat and to protect feline populations against a broad range of virus infections.",2012 Aug 20,"['Robert-Tissot, Céline', 'Rüegger, Vera L', 'Cattori, Valentino', 'Meli, Marina L', 'Riond, Barbara', 'Moore, Peter F', 'Engels, Monika', 'Franchini, Marco', 'Hofmann-Lehmann, Regina', 'Lutz, Hans']",Vet Res,,,True
0e5c57371f4f2cf8e3d56871a391c25ee43aaa4f,PMC,Lycorine induces cell-cycle arrest in the G0/G1 phase in K562 cells via HDAC inhibition,http://dx.doi.org/10.1186/1475-2867-12-49,PMC3537594,23176676,CC BY,"BACKGROUND: Lycorine, a natural alkaloid extracted from Amaryllidaceae, has shown various pharmacological effects. Recent studies have focused on the potential antitumor activity of lycorine. In our previous study, we found that lycorine decrease the cell viability of leukemia HL-60 cells and multiple myeloma KM3 cells and induces cell apoptosis. However, the effect and molecular mechanism of lycorine on human chronic myelocytic leukemia cells has yet to be determined. METHODS: Human chronic myelocytic leukemia cells K562 were treated with lycorine. Cell viability was monitored using the method of CCK-8. The histone deacetylase (HDAC) enzymatic activity was detected by HDAC colorimetric assay, and the cell cycle was analyzed by flow cytometry. The expression of cell-cycle related proteins were identified using Western blot. RESULTS: In the present study, we further revealed that lycorine can inhibit the proliferation of K562 cells. Analysis of HDAC activity showed that lycroine decreases HDAC enzymatic activities in K562 cells in a dose-dependent manner. Inhibition of HDAC activity has been associated with cell-cycle arrest and growth inhibition. We evaluated the cell cycle distribution after lycorine treatment and found that lycorine causes cell-cycle arrest in the G0/G1 phase. To investigate the mechanism behind this cell cycle arrest, G1-related proteins were assayed by Western blot. After lycorine treatment, cyclin D1 and cyclin-dependent kinase 4 expressions were inhibited and retinoblastoma protein phosphorylation was reduced. Lycorine treatment also significantly upregulated the expression of p53 and its target gene product, p21. CONCLUSIONS: These results suggest that inhibition of HDAC activity is responsible for at least part of the induction of cell-cycle arrest in the G0/G1 phase by lycorine and provide a mechanistic framework for further exploring the use of lycorine as a novel antitumor agent.",2012 Nov 23,"['Li, Lv', 'Dai, Hong-Juan', 'Ye, Mao', 'Wang, Shu-Ling', 'Xiao, Xiao-Juan', 'Zheng, Jie', 'Chen, Hui-Yong', 'Luo, Yu-hao', 'Liu, Jing']",Cancer Cell Int,,,True
957d77501f48dcd482bfa9491c169ffb781a3277,PMC,Low Levels of Mannan-Binding Lectin or Ficolins Are Not Associated with an Increased Risk of Cytomegalovirus Disease in HIV-Infected Patients,http://dx.doi.org/10.1371/journal.pone.0051983,PMC3537714,23308103,CC BY,"BACKGROUND: In HIV-infected patients, prediction of Cytomegalovirus (CMV) disease remains difficult. A protective role of mannan-binding lectin (MBL) and ficolins against CMV disease has been reported after transplantation, but the impact in HIV-infected patients is unclear. METHODS: In a case-control study nested within the Swiss HIV Cohort Study, we investigated associations between plasma levels of MBL/ficolins and CMV disease. We compared HIV-infected patients with CMV disease (cases) to CMV-seropositive patients without CMV disease (controls) matched for CD4 T-cells, sampling time, and use of combination antiretroviral therapy. MBL and M-ficolin, L-ficolin, and H-ficolin were quantified using ELISA. RESULTS: We analysed 105 cases and 105 matched controls. CMV disease was neither associated with MBL (odds ratio [OR] 1.03 per log(10) ng/mL increase (95% CI 0.73–1.45)) nor with ficolins (OR per log(10) ng/mL increase 0.66 (95% CI 0.28–1.52), 2.34 (95% CI 0.44–12.36), and 0.89 (95% CI 0.26–3.03) for M-ficolin, L-ficolin, and H-ficolin, respectively). We found no evidence of a greater association between MBL and CMV disease in patients with low CD4 counts; however in the multivariable analysis, CMV disease was more likely in patients with an increased HIV RNA (OR 1.53 per log(10) copies/mL; 95% CI 1.08–2.16), or a shorter duration of HIV-infection (OR 0.91 per year; 95% CI 0.84–0.98). CONCLUSIONS: CMV disease is not associated with low levels of MBL/ficolins, suggesting a lack of a protective role in HIV-infected patients.",2013 Jan 4,"['Egli, Adrian', 'Schäfer, Juliane', 'Osthoff, Michael', 'Thiel, Steffen', 'Mikkelsen, Christina', 'Rauch, Andri', 'Hirsch, Hans H.', 'Bucher, Heiner C.', 'Young, James', 'Jensenius, Jens C.', 'Battegay, Manuel', 'Trendelenburg, Marten', None]",PLoS One,,,True
415ccc587d634fc429ac080cf06694f78621ef73,PMC,"Household transmission of respiratory viruses – assessment of viral, individual and household characteristics in a population study of healthy Australian adults",http://dx.doi.org/10.1186/1471-2334-12-345,PMC3538067,23231698,CC BY,"BACKGROUND: Household transmission of influenza-like illness (ILI) may vary with viral and demographic characteristics. We examined the effect of these factors in a population-based sample of adults with ILI. METHODS: We conducted a prospective cohort study in community-dwelling Australian adults nested within an influenza vaccine effectiveness trial. On presentation with ILI, participants were swabbed for a range of respiratory viruses and asked to return a questionnaire collecting details of household members with or without similar symptoms. We used logistic and Poisson regression to assess the key characteristics of household transmission. RESULTS: 258 participants from multi-occupancy households experienced 279 ILI episodes and returned a questionnaire. Of these, 183 were the primary case in the household allowing assessment of factors associated with transmission. Transmission was significantly associated in univariate analyses with female sex (27% vs. 13%, risk ratio (RR) = 2.13 (1.08, 4.21)) and the presence of a child in the house (33% vs. 17%, RR = 1.90 (1.11, 3.26)). The secondary household attack proportion (SHAP) was 0.14, higher if influenza was isolated (RR = 2.1 (1.0, 4.5)). Vaccinated participants who nonetheless became infected with influenza had a higher SHAP (Incidence RR = 5.24 (2.17, 12.6)). CONCLUSIONS: The increased SHAP in households of vaccinated participants who nonetheless had confirmed influenza infection supports the hypothesis that in years of vaccine mismatch, not only is influenza vaccine less protective for the vaccine recipient, but that the population’s immunity is also lower.",2012 Dec 11,"['McCaw, James M', 'Howard, Peter F', 'Richmond, Peter C', 'Nissen, Michael', 'Sloots, Theo', 'Lambert, Stephen B', 'Lai, Michael', 'Greenberg, Michael', 'Nolan, Terry', 'McVernon, Jodie']",BMC Infect Dis,,,True
af9203fc2b757d830121abc6c7043614b6e9baad,PMC,"Household transmission of respiratory viruses – assessment of viral, individual and household characteristics in a population study of healthy Australian adults",http://dx.doi.org/10.1186/1471-2334-12-345,PMC3538067,23231698,CC BY,"BACKGROUND: Household transmission of influenza-like illness (ILI) may vary with viral and demographic characteristics. We examined the effect of these factors in a population-based sample of adults with ILI. METHODS: We conducted a prospective cohort study in community-dwelling Australian adults nested within an influenza vaccine effectiveness trial. On presentation with ILI, participants were swabbed for a range of respiratory viruses and asked to return a questionnaire collecting details of household members with or without similar symptoms. We used logistic and Poisson regression to assess the key characteristics of household transmission. RESULTS: 258 participants from multi-occupancy households experienced 279 ILI episodes and returned a questionnaire. Of these, 183 were the primary case in the household allowing assessment of factors associated with transmission. Transmission was significantly associated in univariate analyses with female sex (27% vs. 13%, risk ratio (RR) = 2.13 (1.08, 4.21)) and the presence of a child in the house (33% vs. 17%, RR = 1.90 (1.11, 3.26)). The secondary household attack proportion (SHAP) was 0.14, higher if influenza was isolated (RR = 2.1 (1.0, 4.5)). Vaccinated participants who nonetheless became infected with influenza had a higher SHAP (Incidence RR = 5.24 (2.17, 12.6)). CONCLUSIONS: The increased SHAP in households of vaccinated participants who nonetheless had confirmed influenza infection supports the hypothesis that in years of vaccine mismatch, not only is influenza vaccine less protective for the vaccine recipient, but that the population’s immunity is also lower.",2012 Dec 11,"['McCaw, James M', 'Howard, Peter F', 'Richmond, Peter C', 'Nissen, Michael', 'Sloots, Theo', 'Lambert, Stephen B', 'Lai, Michael', 'Greenberg, Michael', 'Nolan, Terry', 'McVernon, Jodie']",BMC Infect Dis,,,False
25d4af008525a27cff170cac5381937b1a65dc83,PMC,Viral etiologies of lower respiratory tract infections among Egyptian children under five years of age,http://dx.doi.org/10.1186/1471-2334-12-350,PMC3538156,23237512,CC BY,"BACKGROUND: Lower respiratory tract infections (LRTI) are responsible for a considerable number of deaths among children, particularly in developing countries. In Egypt and the Middle East region, there is a lack of data regarding the viral causes of LRTI. In this study, we aimed to identify the relative prevalence of various respiratory viruses that contribute to LRTIs in young children. Although, nucleic acid-based methods have gained importance as a sensitive tool to determine the viral infections, their use is limited because of their prohibitive cost in low-income countries. Therefore, we applied three different laboratory methods, and presented the different virus prevalence patterns detected by each method. METHODS: We collected nasopharyngeal aspirate samples, demographic data and, clinical data from 450 children under five years of age who presented with LRTI at Abou El Reesh hospital in Cairo during a one-year period. To identify the viral causes of the LRTI we used direct fluorescence assay, real-time reverse-transcriptase polymerase chain reaction (rt-RT-PCR), and shell vial culture. We tested for eight major respiratory viruses. RESULTS: Two hundred sixty-nine patients (59.9%) had a viral infection, among which 10.8% had a co-infection with two or more viruses. By all three methods, respiratory syncytial virus (RSV) was the most predominant, and parainfluenza virus type 2 (HPIV-2), influenza B virus (FLUBV) were the least predominant. Other viral prevalence patterns differed according to the detection method used. The distribution of various viruses among different age groups and seasonal distribution of the viruses were also determined. CONCLUSIONS: RSV and human adenovirus were the most common respiratory viruses detected by rt-RT-PCR. Co-infections were found to be frequent among children and the vast majority of co-infections were detected by nucleic acid-based detection assays.",2012 Dec 13,"['Shafik, Caroline F', 'Mohareb, Emad W', 'Yassin, Aymen S', 'Amin, Madgy A', 'El Kholy, Amani', 'El-Karaksy, Hanaa', 'Youssef, Fouad G']",BMC Infect Dis,,,True
ec645bdfc64cfa6c23a1cf9bf56950c2f9348ec1,PMC,Viral etiologies of lower respiratory tract infections among Egyptian children under five years of age,http://dx.doi.org/10.1186/1471-2334-12-350,PMC3538156,23237512,CC BY,"BACKGROUND: Lower respiratory tract infections (LRTI) are responsible for a considerable number of deaths among children, particularly in developing countries. In Egypt and the Middle East region, there is a lack of data regarding the viral causes of LRTI. In this study, we aimed to identify the relative prevalence of various respiratory viruses that contribute to LRTIs in young children. Although, nucleic acid-based methods have gained importance as a sensitive tool to determine the viral infections, their use is limited because of their prohibitive cost in low-income countries. Therefore, we applied three different laboratory methods, and presented the different virus prevalence patterns detected by each method. METHODS: We collected nasopharyngeal aspirate samples, demographic data and, clinical data from 450 children under five years of age who presented with LRTI at Abou El Reesh hospital in Cairo during a one-year period. To identify the viral causes of the LRTI we used direct fluorescence assay, real-time reverse-transcriptase polymerase chain reaction (rt-RT-PCR), and shell vial culture. We tested for eight major respiratory viruses. RESULTS: Two hundred sixty-nine patients (59.9%) had a viral infection, among which 10.8% had a co-infection with two or more viruses. By all three methods, respiratory syncytial virus (RSV) was the most predominant, and parainfluenza virus type 2 (HPIV-2), influenza B virus (FLUBV) were the least predominant. Other viral prevalence patterns differed according to the detection method used. The distribution of various viruses among different age groups and seasonal distribution of the viruses were also determined. CONCLUSIONS: RSV and human adenovirus were the most common respiratory viruses detected by rt-RT-PCR. Co-infections were found to be frequent among children and the vast majority of co-infections were detected by nucleic acid-based detection assays.",2012 Dec 13,"['Shafik, Caroline F', 'Mohareb, Emad W', 'Yassin, Aymen S', 'Amin, Madgy A', 'El Kholy, Amani', 'El-Karaksy, Hanaa', 'Youssef, Fouad G']",BMC Infect Dis,,,False
ec541d386273c4ba8629d3bebf20e7ffa635aeac,PMC,Viral etiologies of lower respiratory tract infections among Egyptian children under five years of age,http://dx.doi.org/10.1186/1471-2334-12-350,PMC3538156,23237512,CC BY,"BACKGROUND: Lower respiratory tract infections (LRTI) are responsible for a considerable number of deaths among children, particularly in developing countries. In Egypt and the Middle East region, there is a lack of data regarding the viral causes of LRTI. In this study, we aimed to identify the relative prevalence of various respiratory viruses that contribute to LRTIs in young children. Although, nucleic acid-based methods have gained importance as a sensitive tool to determine the viral infections, their use is limited because of their prohibitive cost in low-income countries. Therefore, we applied three different laboratory methods, and presented the different virus prevalence patterns detected by each method. METHODS: We collected nasopharyngeal aspirate samples, demographic data and, clinical data from 450 children under five years of age who presented with LRTI at Abou El Reesh hospital in Cairo during a one-year period. To identify the viral causes of the LRTI we used direct fluorescence assay, real-time reverse-transcriptase polymerase chain reaction (rt-RT-PCR), and shell vial culture. We tested for eight major respiratory viruses. RESULTS: Two hundred sixty-nine patients (59.9%) had a viral infection, among which 10.8% had a co-infection with two or more viruses. By all three methods, respiratory syncytial virus (RSV) was the most predominant, and parainfluenza virus type 2 (HPIV-2), influenza B virus (FLUBV) were the least predominant. Other viral prevalence patterns differed according to the detection method used. The distribution of various viruses among different age groups and seasonal distribution of the viruses were also determined. CONCLUSIONS: RSV and human adenovirus were the most common respiratory viruses detected by rt-RT-PCR. Co-infections were found to be frequent among children and the vast majority of co-infections were detected by nucleic acid-based detection assays.",2012 Dec 13,"['Shafik, Caroline F', 'Mohareb, Emad W', 'Yassin, Aymen S', 'Amin, Madgy A', 'El Kholy, Amani', 'El-Karaksy, Hanaa', 'Youssef, Fouad G']",BMC Infect Dis,,,False
bcd9208e1cff6a9d5e3af17745299ceea1479529,PMC,Purification and Characterisation of Immunoglobulins from the Australian Black Flying Fox (Pteropus alecto) Using Anti-Fab Affinity Chromatography Reveals the Low Abundance of IgA,http://dx.doi.org/10.1371/journal.pone.0052930,PMC3538733,23308125,CC BY,"There is now an overwhelming body of evidence that implicates bats in the dissemination of a long list of emerging and re-emerging viral agents, often causing illnesses or death in both animals and humans. Despite this, there is a paucity of information regarding the immunological mechanisms by which bats coexist with highly pathogenic viruses. Immunoglobulins are major components of the adaptive immune system. Early studies found bats may have quantitatively lower antibody responses to model antigens compared to conventional laboratory animals. To further understand the antibody response of bats, the present study purified and characterised the major immunoglobulin classes from healthy black flying foxes, Pteropus alecto. We employed a novel strategy, where IgG was initially purified and used to generate anti-Fab specific antibodies. Immobilised anti-Fab specific antibodies were then used to capture other immunoglobulins from IgG depleted serum. While high quantities of IgM were successfully isolated from serum, IgA was not. Only trace quantities of IgA were detected in the serum by mass spectrometry. Immobilised ligands specific to IgA (Jacalin, Peptide M and staphylococcal superantigen-like protein) also failed to capture P. alecto IgA from serum. IgM was the second most abundant serum antibody after IgG. A survey of mucosal secretions found IgG was the dominant antibody class rather than IgA. Our study demonstrates healthy P. alecto bats have markedly less serum IgA than expected. Higher quantities of IgG in mucosal secretions may be compensation for this low abundance or lack of IgA. Knowledge and reagents developed within this study can be used in the future to examine class-specific antibody response within this important viral host.",2013 Jan 7,"['Wynne, James W.', 'Di Rubbo, Antonio', 'Shiell, Brian J.', 'Beddome, Gary', 'Cowled, Christopher', 'Peck, Grantley R.', 'Huang, Jing', 'Grimley, Samantha L.', 'Baker, Michelle L.', 'Michalski, Wojtek P.']",PLoS One,,,True
45edbd85cb93950fecbc8da86f684a9e45c1d8f1,PMC,Inhibitory Influence of Enterococcus faecium on the Propagation of Swine Influenza A Virus In Vitro,http://dx.doi.org/10.1371/journal.pone.0053043,PMC3538747,23308134,CC BY,"The control of infectious diseases such as swine influenza viruses (SwIV) plays an important role in food production both from the animal health and from the public health point of view. Probiotic microorganisms and other health improving food supplements have been given increasing attention in recent years, but, no information on the effects of probiotics on swine influenza virus is available. Here we address this question by assessing the inhibitory potential of the probiotic Enterococcus faecium NCIMB 10415 (E. faecium) on the replication of two porcine strains of influenza virus (H1N1 and H3N2 strain) in a continuous porcine macrophage cell line (3D4/21) and in MDBK cells. Cell cultures were treated with E. faecium at the non-toxic concentration of 1×10(6) CFU/ml in growth medium for 60 to 90 min before, during and after SwIV infection. After further incubation of cultures in probiotic-free growth medium, cell viability and virus propagation were determined at 48 h or 96 h post infection. The results obtained reveal an almost complete recovery of viability of SwIV infected cells and an inhibition of virus multiplication by up to four log units in the E. faecium treated cells. In both 3D4/21- and MDBK-cells a 60 min treatment with E. faecium stimulated nitric oxide (NO) release which is in line with published evidence for an antiviral function of NO. Furthermore, E. faecium caused a modified cellular expression of selected mediators of defence in 3D4-cells: while the expression of TNF-α, TLR-3 and IL-6 were decreased in the SwIV-infected and probiotic treated cells, IL-10 was found to be increased. Since we obtained experimental evidence for the direct adsorptive trapping of SwIV through E. faecium, this probiotic microorganism inhibits influenza viruses by at least two mechanisms, direct physical interaction and strengthening of innate defence at the cellular level.",2013 Jan 7,"['Wang, Zhenya', 'Chai, Weidong', 'Burwinkel, Michael', 'Twardziok, Sven', 'Wrede, Paul', 'Palissa, Christiane', 'Esch, Bettina', 'Schmidt, Michael F. G.']",PLoS One,,,True
7139441855f3ac67f104fb9e067b1359c5582fd6,PMC,The Role of Viral Population Diversity in Adaptation of Bovine Coronavirus to New Host Environments,http://dx.doi.org/10.1371/journal.pone.0052752,PMC3538757,23308119,CC0,"The high mutation rate of RNA viruses enables a diverse genetic population of viral genotypes to exist within a single infected host. In-host genetic diversity could better position the virus population to respond and adapt to a diverse array of selective pressures such as host-switching events. Multiple new coronaviruses, including SARS, have been identified in human samples just within the last ten years, demonstrating the potential of coronaviruses as emergent human pathogens. Deep sequencing was used to characterize genomic changes in coronavirus quasispecies during simulated host-switching. Three bovine nasal samples infected with bovine coronavirus were used to infect human and bovine macrophage and lung cell lines. The virus reproduced relatively well in macrophages, but the lung cell lines were not infected efficiently enough to allow passage of non lab-adapted samples. Approximately 12 kb of the genome was amplified before and after passage and sequenced at average coverages of nearly 950×(454 sequencing) and 38,000×(Illumina). The consensus sequence of many of the passaged samples had a 12 nucleotide insert in the consensus sequence of the spike gene, and multiple point mutations were associated with the presence of the insert. Deep sequencing revealed that the insert was present but very rare in the unpassaged samples and could quickly shift to dominate the population when placed in a different environment. The insert coded for three arginine residues, occurred in a region associated with fusion entry into host cells, and may allow infection of new cell types via heparin sulfate binding. Analysis of the deep sequencing data indicated that two distinct genotypes circulated at different frequency levels in each sample, and support the hypothesis that the mutations present in passaged strains were “selected” from a pre-existing pool rather than through de novo mutation and subsequent population fixation.",2013 Jan 7,"['Borucki, Monica K.', 'Allen, Jonathan E.', 'Chen-Harris, Haiyin', 'Zemla, Adam', 'Vanier, Gilda', 'Mabery, Shalini', 'Torres, Clinton', 'Hullinger, Pamela', 'Slezak, Tom']",PLoS One,,,True
16eb672447620efa83aa59f913d690a95240f488,PMC,The “sweet” side of a long pentraxin: how glycosylation affects PTX3 functions in innate immunity and inflammation,http://dx.doi.org/10.3389/fimmu.2012.00407,PMC3539679,23316195,CC BY,"Innate immunity represents the first line of defense against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognize pathogen-associated molecular patterns and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a non-redundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the crossroad between innate immunity, inflammation, and female fertility. The human PTX3 protein contains a single N-glycosylation site that is fully occupied by complex type oligosaccharides, mainly fucosylated and sialylated biantennary glycans. Glycosylation has been implicated in a number of PTX3 activities, including neutralization of influenza viruses, modulation of the complement system, and attenuation of leukocyte recruitment. Therefore, this post translational modification might act as a fine tuner of PTX3 functions in native immunity and inflammation. Here we review the studies on PTX3, with emphasis on the glycan-dependent mechanisms underlying pathogen recognition and crosstalk with other components of the innate immune system.",2013 Jan 7,"['Inforzato, Antonio', 'Reading, Patrick C.', 'Barbati, Elisa', 'Bottazzi, Barbara', 'Garlanda, Cecilia', 'Mantovani, Alberto']",Front Immunol,,,True
2d5fdcbc3c2b82ecef0748012b73fc1aa7a2ad96,PMC,A Critical HA1 Neutralizing Domain of H5N1 Influenza in an Optimal Conformation Induces Strong Cross-Protection,http://dx.doi.org/10.1371/journal.pone.0053568,PMC3539987,23320093,CC BY,"The highly pathogenic avian influenza (HPAI) H5N1 viruses, especially the laboratory-generated H5N1 mutants, have demonstrated the potential to cross the species barrier and infect mammals and humans. Consequently, the design of an effective and safe anti-H5N1 vaccine is essential. We previously demonstrated that the full-length hemagglutinin 1 (HA1) could induce significant neutralizing antibody response and protection. Here, we intended to identify the critical neutralizing domain (CND) in an optimal conformation that can elicit strong cross-neutralizing antibodies and protection against divergent H5N1 strains. We thus constructed six recombinant proteins covering different regions of HA1 of A/Anhui/1/2005(H5N1), each of which was fused with foldon (Fd) and Fc of human IgG. We found that the critical fragment fused with Fd/Fc (HA-13–263-Fdc, H5 numbering) that could elicit the strongest neutralizing antibody response is located in the N-terminal region of HA1 (residues 13–263), which covers the receptor-binding domain (RBD, residues 112–263). We then constructed three additional recombinants fused with Fd plus His tag (HA-13–263-Fd-His), Fc only (HA-13–263-Fc), and His tag only (HA-13–263-His), respectively. We found that the HA-13–263-Fdc, which formed an oligomeric conformation, induced the strongest neutralizing antibody response and cross-protection against challenges of two tested H5N1 virus strains covering clade 1: A/VietNam/1194/2004 (VN/1194) or clade 2.3.4: A/Shenzhen/406H/06 (SZ/406H), while HA-13–263-Fc dimer and HA-13–263-Fd-His trimer elicited higher neutralizing antibody response and protection than HA-13–263-His monomer. These results suggest that the oligomeric form of the CND containing the RBD can be further developed as an effective and safe vaccine for cross-protection against divergent strains of H5N1 viruses.",2013 Jan 8,"['Du, Lanying', 'Zhao, Guangyu', 'Sun, Shihui', 'Zhang, Xiujuan', 'Zhou, Xiaojun', 'Guo, Yan', 'Li, Ye', 'Zhou, Yusen', 'Jiang, Shibo']",PLoS One,,,True
2e32842d3ebcee3ffaf4b6822dbac0f41f82130a,PMC,Activation of the Cellular Unfolded Protein Response by Recombinant Adeno-Associated Virus Vectors,http://dx.doi.org/10.1371/journal.pone.0053845,PMC3540029,23320106,CC BY,"The unfolded protein response (UPR) is a stress-induced cyto-protective mechanism elicited towards an influx of large amount of proteins in the endoplasmic reticulum (ER). In the present study, we evaluated if AAV manipulates the UPR pathways during its infection. We first examined the role of the three major UPR axes, namely, endoribonuclease inositol-requiring enzyme-1 (IRE1α), activating transcription factor 6 (ATF6) and PKR-like ER kinase (PERK) in AAV infected cells. Total RNA from mock or AAV infected HeLa cells were used to determine the levels of 8 different ER-stress responsive transcripts from these pathways. We observed a significant up-regulation of IRE1α (up to 11 fold) and PERK (up to 8 fold) genes 12–48 hours after infection with self-complementary (sc)AAV2 but less prominent with single-stranded (ss)AAV2 vectors. Further studies demonstrated that scAAV1 and scAAV6 also induce cellular UPR in vitro, with AAV1 vectors activating the PERK pathway (3 fold) while AAV6 vectors induced a significant increase on all the three major UPR pathways [6–16 fold]. These data suggest that the type and strength of UPR activation is dependent on the viral capsid. We then examined if transient inhibition of UPR pathways by RNA interference has an effect on AAV transduction. siRNA mediated silencing of PERK and IRE1α had a modest effect on AAV2 and AAV6 mediated gene expression (∼1.5–2 fold) in vitro. Furthermore, hepatic gene transfer of scAAV2 vectors in vivo, strongly elevated IRE1α and PERK pathways (2 and 3.5 fold, respectively). However, when animals were pre-treated with a pharmacological UPR inhibitor (metformin) during scAAV2 gene transfer, the UPR signalling and its subsequent inflammatory response was attenuated concomitant to a modest 2.8 fold increase in transgene expression. Collectively, these data suggest that AAV vectors activate the cellular UPR pathways and their selective inhibition may be beneficial during AAV mediated gene transfer.",2013 Jan 8,"['Balakrishnan, Balaji', 'Sen, Dwaipayan', 'Hareendran, Sangeetha', 'Roshini, Vaani', 'David, Sachin', 'Srivastava, Alok', 'Jayandharan, Giridhara R.']",PLoS One,,,True
54125da57282e24d5bcc4c1b60fa54ba1ad784be,PMC,Targeting Herpetic Keratitis by Gene Therapy,http://dx.doi.org/10.1155/2012/594869,PMC3541562,23326647,CC BY,"Ocular gene therapy is rapidly becoming a reality. By November 2012, approximately 28 clinical trials were approved to assess novel gene therapy agents. Viral infections such as herpetic keratitis caused by herpes simplex virus 1 (HSV-1) can cause serious complications that may lead to blindness. Recurrence of the disease is likely and cornea transplantation, therefore, might not be the ideal therapeutic solution. This paper will focus on the current situation of ocular gene therapy research against herpetic keratitis, including the use of viral and nonviral vectors, routes of delivery of therapeutic genes, new techniques, and key research strategies. Whereas the correction of inherited diseases was the initial goal of the field of gene therapy, here we discuss transgene expression, gene replacement, silencing, or clipping. Gene therapy of herpetic keratitis previously reported in the literature is screened emphasizing candidate gene therapy targets. Commonly adopted strategies are discussed to assess the relative advantages of the protective therapy using antiviral drugs and the common gene therapy against long-term HSV-1 ocular infections signs, inflammation and neovascularization. Successful gene therapy can provide innovative physiological and pharmaceutical solutions against herpetic keratitis.",2012 Dec 26,"['Elbadawy, Hossein Mostafa', 'Gailledrat, Marine', 'Desseaux, Carole', 'Ponzin, Diego', 'Ferrari, Stefano']",J Ophthalmol,,,True
b90bc6d84f996cb85c97b94b98f976c7d93367a6,PMC,"Schmallenberg Virus Pathogenesis, Tropism and Interaction with the Innate Immune System of the Host",http://dx.doi.org/10.1371/journal.ppat.1003133,PMC3542112,23326235,CC BY,"Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV.",2013 Jan 10,"['Varela, Mariana', 'Schnettler, Esther', 'Caporale, Marco', 'Murgia, Claudio', 'Barry, Gerald', 'McFarlane, Melanie', 'McGregor, Eva', 'Piras, Ilaria M.', 'Shaw, Andrew', 'Lamm, Catherine', 'Janowicz, Anna', 'Beer, Martin', 'Glass, Mandy', 'Herder, Vanessa', 'Hahn, Kerstin', 'Baumgärtner, Wolfgang', 'Kohl, Alain', 'Palmarini, Massimo']",PLoS Pathog,,,True
bb7718e2a9a390578e8d3f5ea081f08d3fd17185,PMC,Viral and Bacterial Interactions in the Upper Respiratory Tract,http://dx.doi.org/10.1371/journal.ppat.1003057,PMC3542149,23326226,CC BY,"Respiratory infectious diseases are mainly caused by viruses or bacteria that often interact with one another. Although their presence is a prerequisite for subsequent infections, viruses and bacteria may be present in the nasopharynx without causing any respiratory symptoms. The upper respiratory tract hosts a vast range of commensals and potential pathogenic bacteria, which form a complex microbial community. This community is assumed to be constantly subject to synergistic and competitive interspecies interactions. Disturbances in the equilibrium, for instance due to the acquisition of new bacteria or viruses, may lead to overgrowth and invasion. A better understanding of the dynamics between commensals and pathogens in the upper respiratory tract may provide better insight into the pathogenesis of respiratory diseases. Here we review the current knowledge regarding specific bacterial–bacterial and viral–bacterial interactions that occur in the upper respiratory niche, and discuss mechanisms by which these interactions might be mediated. Finally, we propose a theoretical model to summarize and illustrate these mechanisms.",2013 Jan 10,"['Bosch, Astrid A. T. M.', 'Biesbroek, Giske', 'Trzcinski, Krzysztof', 'Sanders, Elisabeth A. M.', 'Bogaert, Debby']",PLoS Pathog,,,True
360e2ae0c8c522d48cb5414c1e982d96e40165b6,PMC,A Monoclonal Antibody-Based Copro-ELISA Kit for Canine Echinococcosis to Support the PAHO Effort for Hydatid Disease Control in South America,http://dx.doi.org/10.1371/journal.pntd.0001967,PMC3542170,23326610,CC BY,"Cystic echinococcosis is still a major concern in South America. While some regions show advances in the control of the disease, others have among the highest incidence in the world. To reverse this situation the Pan American Health Organization (PAHO) has launched a regional project on cystic echinococcosis control and surveillance. An early concern of the program was the lack of a standardized diagnostic tool to monitor infection in dogs, a key target of control programs. Under this premise, we have developed a new copro-ELISA test after extensive screening of a large panel of monoclonal antibodies (MAbs) and polyclonal sera, which performs with high standards of sensitivity (92.6%) and specificity (86.4%) as established by necropsy diagnosis of dogs. The key component of the test, MAbEg9 has a convenient IgG isotype and reacts with a periodate-resistant epitope found in high molecular weight components of the worm. Time-course analysis of experimentally infected dogs showed that even animals with a very low number of parasites could be detected as early as day 20 post infection. The test was formulated in a ready-to-use kit format with proven stability of each component for a minimum of 3 months at room temperature. This characteristic facilitates its standardized use and shipping to other laboratories, which was demonstrated by the identical results obtained by two different laboratories in Peru and our own laboratory when a large number of field samples were analyzed independently in a blind fashion.",2013 Jan 10,"['Morel, Noelia', 'Lassabe, Gabriel', 'Elola, Susana', 'Bondad, Mauricio', 'Herrera, Silvia', 'Marí, Carlos', 'Last, Jerold A.', 'Jensen, Oscar', 'Gonzalez-Sapienza, Gualberto']",PLoS Negl Trop Dis,,,True
0d673eba8d23c47646d0f5b69937ee87716aa1df,PMC,Co-circulation of diverse paramyxoviruses in an urban African fruit bat population,http://dx.doi.org/10.1099/vir.0.039339-0,PMC3542712,22205718,CC BY,"Bats constitute a reservoir of zoonotic infections and some bat paramyxoviruses are capable of cross-species transmission, often with fatal consequences. Determining the level of viral diversity in reservoir populations is fundamental to understanding and predicting viral emergence. This is particularly relevant for RNA viruses where the adaptive mutations required for cross-species transmission can be present in the reservoir host. We report the use of non-invasively collected, pooled, neat urine samples as a robust sample type for investigating paramyxoviruses in bat populations. Using consensus PCR assays we have detected a high incidence and genetic diversity of novel paramyxoviruses in an urban fruit bat population over a short period of time. This may suggest a similarly unique relationship between bats and the members of the family Paramyxoviridae as proposed for some other viral families. Additionally, the high rate of bat–human contact at the study site calls for the zoonotic potential of the detected viruses to be investigated further.",2012 Apr,"['Baker, K. S.', 'Todd, S.', 'Marsh, G.', 'Fernandez-Loras, A.', 'Suu-Ire, R.', 'Wood, J. L. N.', 'Wang, L. F.', 'Murcia, P. R.', 'Cunningham, A. A.']",J Gen Virol,,,True
5afa333a59a3d818c758dbc752463b90436a1c57,PMC,ISG56/IFIT1 is primarily responsible for interferon-induced changes to patterns of parainfluenza virus type 5 transcription and protein synthesis,http://dx.doi.org/10.1099/vir.0.046797-0,PMC3542720,23052390,CC BY,"Interferon (IFN) induces an antiviral state in cells that results in alterations of the patterns and levels of parainfluenza virus type 5 (PIV5) transcripts and proteins. This study reports that IFN-stimulated gene 56/IFN-induced protein with tetratricopeptide repeats 1 (ISG56/IFIT1) is primarily responsible for these effects of IFN. It was shown that treating cells with IFN after infection resulted in an increase in virus transcription but an overall decrease in virus protein synthesis. As there was no obvious decrease in the overall levels of cellular protein synthesis in infected cells treated with IFN, these results suggested that ISG56/IFIT1 selectively inhibits the translation of viral mRNAs. This conclusion was supported by in vitro translation studies. Previous work has shown that ISG56/IFIT1 can restrict the replication of viruses lacking a 2′-O-methyltransferase activity, an enzyme that methylates the 2′-hydroxyl group of ribose sugars in the 5′-cap structures of mRNA. However, the data in the current study strongly suggested that PIV5 mRNAs are methylated at the 2′-hydroxyl group and thus that ISG56/IFIT1 selectively inhibits the translation of PIV5 mRNA by some as yet unrecognized mechanism. It was also shown that ISG56/IFIT1 is primarily responsible for the IFN-induced inhibition of PIV5.",2013 Jan,"['Andrejeva, J.', 'Norsted, H.', 'Habjan, M.', 'Thiel, V.', 'Goodbourn, S.', 'Randall, R. E.']",J Gen Virol,,,True
f5bdf18567bb3760e1ce05008135f0270badbd5c,PMC,Pre-existing immunity against vaccine vectors – friend or foe?,http://dx.doi.org/10.1099/mic.0.049601-0,PMC3542731,23175507,CC BY,"Over the last century, the successful attenuation of multiple bacterial and viral pathogens has led to an effective, robust and safe form of vaccination. Recently, these vaccines have been evaluated as delivery vectors for heterologous antigens, as a means of simultaneous vaccination against two pathogens. The general consensus from published studies is that these vaccine vectors have the potential to be both safe and efficacious. However, some of the commonly employed vectors, for example Salmonella and adenovirus, often have pre-existing immune responses in the host and this has the potential to modify the subsequent immune response to a vectored antigen. This review examines the literature on this topic, and concludes that for bacterial vectors there can in fact, in some cases, be an enhancement in immunogenicity, typically humoral, while for viral vectors pre-existing immunity is a hindrance for subsequent induction of cell-mediated responses.",2013 Jan,"['Saxena, Manvendra', 'Van, Thi Thu Hao', 'Baird, Fiona J.', 'Coloe, Peter J.', 'Smooker, Peter M.']",Microbiology,,,True
f4a7339511490ed2b84a8b9189b5f2f05ff57082,PMC,Non-canonical translation in RNA viruses,http://dx.doi.org/10.1099/vir.0.042499-0,PMC3542737,22535777,CC BY,"Viral protein synthesis is completely dependent upon the translational machinery of the host cell. However, many RNA virus transcripts have marked structural differences from cellular mRNAs that preclude canonical translation initiation, such as the absence of a 5′ cap structure or the presence of highly structured 5′UTRs containing replication and/or packaging signals. Furthermore, whilst the great majority of cellular mRNAs are apparently monocistronic, RNA viruses must often express multiple proteins from their mRNAs. In addition, RNA viruses have very compact genomes and are under intense selective pressure to optimize usage of the available sequence space. Together, these features have driven the evolution of a plethora of non-canonical translational mechanisms in RNA viruses that help them to meet these challenges. Here, we review the mechanisms utilized by RNA viruses of eukaryotes, focusing on internal ribosome entry, leaky scanning, non-AUG initiation, ribosome shunting, reinitiation, ribosomal frameshifting and stop-codon readthrough. The review will highlight recently discovered examples of unusual translational strategies, besides revisiting some classical cases.",2012 Jul,"['Firth, Andrew E.', 'Brierley, Ian']",J Gen Virol,,,True
0043d044273b8eb1585d3a66061e9b4e03edc062,PMC,"Evaluation of the tuberculosis programme in Ningxia Hui Autonomous region, the People’s Republic of China: a retrospective case study",http://dx.doi.org/10.1186/1471-2458-12-1110,PMC3543161,23259484,CC BY,"BACKGROUND: Tuberculosis is a devastating disease due to its rapid transmission and high rate of mortality. Ningxia Hui Autonomous Region (NHAR), located in the North-west, is one of the poorest provinces in China and national surveys have shown TB has been hyper endemic in NHAR for several decades. As no active surveys had been undertaken since the initiation of the DOTS control program across all of NHAR. METHODS: A retrospective study was undertaken of all clinical records of TB patients registered from January 2005 to September 2009. Poisson regression was performed to investigate the change in incidence over time and accounted for age, sex and county. Length of time on treatment, disease severity and patient delay were assessed by county. RESULTS: More than 30% of patients had been on treatment for over 12 months and 10% for over 3 years, reflecting drug-resistance or failure of DOTS. More than 93% of patients had grade III disease at time of diagnosis and >15% of patients had severe disease grade IV-V in some NHAR counties. Further, 8.8% of patients were not diagnosed for over 6 months from the onset of symptoms; this was as high as 20% in some counties. The reported incidence of TB is most likely grossly underestimated and the data indicate TB is a major public health concern in NHAR. CONCLUSIONS: It is clear that active surveillance is necessary to determine the full extent of the burden of TB in NHAR. New control and treatment strategies for TB are required that increase awareness in the health-care system and at the individual and community level.",2012 Dec 23,"['Yang, Yu Rong', 'McManus, Donald P', 'Gray, Darren J', 'Wang, Xiao Ling', 'Yang, Shu Kun', 'Ross, Allen G', 'Williams, Gail M', 'Ellis, Magda K']",BMC Public Health,,,True
5a69605f00c8bcbe367fe3eeeefa835438f4b955,PMC,"Treatment of Common Cold Patients with the Shi-Cha Capsule: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Dose-Escalation Trial",http://dx.doi.org/10.1155/2012/254571,PMC3544370,23346193,CC BY,"This study was designed to determine the therapeutic efficacy and safety of the Shi-cha capsule, a Chinese herbal formula, in the treatment of patients with wind-cold type common cold. In our multi-center, prospective, double-blind, randomized, placebo-controlled, dose-escalation trial, patients with wind-cold type common cold received 0.6 g of Shi-cha capsule plus 0.6 g placebo (group A), 1.2 g of Shi-cha capsule (group B), or 1.2 g placebo (group C), three times daily for 3 days and followed up to 10 days. The primary end point was all symptom duration. The secondary end points were main symptom duration, minor symptom duration, the changes in cumulative symptom score, main symptom score, and minor symptom score 4 days after the treatment, as well as adverse events. A total of 377 patients were recruited and 360 met the inclusive criteria; 120 patients constituted each treatment group. Compared with patients in group C, patients in groups A and B had significant improvement in the all symptom duration, main symptom duration, minor symptom duration, as well as change from baseline of cumulative symptom score, main symptom score, and minor symptom score at day 4. The symptom durations and scores showed slight superiority of group B over group A, although these differences were not statistically significant. There were no differences in adverse events. The Shi-cha capsule is efficacious and safe for the treatment of patients with wind-cold type common cold. Larger trials are required to fully assess the benefits and safety of this treatment for common cold.",2012 Dec 27,"['Chang, Jing', 'Dong, Shou-Jin', 'She, Bin', 'Zhang, Rui-Ming', 'Meng, Mao-Bin', 'Xu, Yan-Ling', 'Wan, Li-Ling', 'Shi, Ke-Hua', 'Pan, Jun-Hun', 'Mao, Bing']",Evid Based Complement Alternat Med,,,False
ec64f7f7ece2c16fb0a4210295b2527714b11ee0,PMC,"Treatment of Common Cold Patients with the Shi-Cha Capsule: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Dose-Escalation Trial",http://dx.doi.org/10.1155/2012/254571,PMC3544370,23346193,CC BY,"This study was designed to determine the therapeutic efficacy and safety of the Shi-cha capsule, a Chinese herbal formula, in the treatment of patients with wind-cold type common cold. In our multi-center, prospective, double-blind, randomized, placebo-controlled, dose-escalation trial, patients with wind-cold type common cold received 0.6 g of Shi-cha capsule plus 0.6 g placebo (group A), 1.2 g of Shi-cha capsule (group B), or 1.2 g placebo (group C), three times daily for 3 days and followed up to 10 days. The primary end point was all symptom duration. The secondary end points were main symptom duration, minor symptom duration, the changes in cumulative symptom score, main symptom score, and minor symptom score 4 days after the treatment, as well as adverse events. A total of 377 patients were recruited and 360 met the inclusive criteria; 120 patients constituted each treatment group. Compared with patients in group C, patients in groups A and B had significant improvement in the all symptom duration, main symptom duration, minor symptom duration, as well as change from baseline of cumulative symptom score, main symptom score, and minor symptom score at day 4. The symptom durations and scores showed slight superiority of group B over group A, although these differences were not statistically significant. There were no differences in adverse events. The Shi-cha capsule is efficacious and safe for the treatment of patients with wind-cold type common cold. Larger trials are required to fully assess the benefits and safety of this treatment for common cold.",2012 Dec 27,"['Chang, Jing', 'Dong, Shou-Jin', 'She, Bin', 'Zhang, Rui-Ming', 'Meng, Mao-Bin', 'Xu, Yan-Ling', 'Wan, Li-Ling', 'Shi, Ke-Hua', 'Pan, Jun-Hun', 'Mao, Bing']",Evid Based Complement Alternat Med,,,True
1008bb267f9b05fcec7b715eab47f4a5c659c7dd,PMC,Teacher led school-based surveillance can allow accurate tracking of emerging infectious diseases - evidence from serial cross-sectional surveys of febrile respiratory illness during the H1N1 2009 influenza pandemic in Singapore,http://dx.doi.org/10.1186/1471-2334-12-336,PMC3544582,23206689,CC BY,"BACKGROUND: Schools are important foci of influenza transmission and potential targets for surveillance and interventions. We compared several school-based influenza monitoring systems with clinic-based influenza-like illness (ILI) surveillance, and assessed the variation in illness rates between and within schools. METHODS: During the initial wave of pandemic H1N1 (pdmH1N1) infections from June to Sept 2009 in Singapore, we collected data on nation-wide laboratory confirmed cases (Sch-LCC) and daily temperature monitoring (Sch-DTM), and teacher-led febrile respiratory illness reporting in 6 sentinel schools (Sch-FRI). Comparisons were made against age-stratified clinic-based influenza-like illness (ILI) data from 23 primary care clinics (GP-ILI) and proportions of ILI testing positive for pdmH1N1 (Lab-ILI) by computing the fraction of cumulative incidence occurring by epidemiological week 30 (when GP-ILI incidence peaked); and cumulative incidence rates between school-based indicators and sero-epidemiological pdmH1N1 incidence (estimated from changes in prevalence of A/California/7/2009 H1N1 hemagglutination inhibition titers ≥ 40 between pre-epidemic and post-epidemic sera). Variation in Sch-FRI rates in the 6 schools was also investigated through a Bayesian hierarchical model. RESULTS: By week 30, for primary and secondary school children respectively, 63% and 79% of incidence for Sch-LCC had occurred, compared with 50% and 52% for GP-ILI data, and 48% and 53% for Sch-FRI. There were 1,187 notified cases and 7,588 episodes in the Sch-LCC and Sch-DTM systems; given school enrollment of 485,723 children, this represented 0.24 cases and 1.6 episodes per 100 children respectively. Mean Sch-FRI rate was 28.8 per 100 children (95% CI: 27.7 to 29.9) in the 6 schools. We estimate from serology that 41.8% (95% CI: 30.2% to 55.9%) of primary and 43.2% (95% CI: 28.2% to 60.8%) of secondary school-aged children were infected. Sch-FRI rates were similar across the 6 schools (23 to 34 episodes per 100 children), but there was widespread variation by classrooms; in the hierarchical model, omitting age and school effects was inconsequential but neglecting classroom level effects led to highly significant reductions in goodness of fit. CONCLUSIONS: Epidemic curves from Sch-FRI were comparable to GP-ILI data, and Sch-FRI detected substantially more infections than Sch-LCC and Sch-DTM. Variability in classroom attack rates suggests localized class-room transmission.",2012 Dec 4,"['Chen, Mark IC', 'Chong, Chia Yin']",BMC Infect Dis,,,True
04c1c40f4464bc035e57d0ecf2f8a033e4e7f466,PMC,"Acute care utilization due to hospitalizations for pediatric lower respiratory tract infections in British Columbia, Canada",http://dx.doi.org/10.1186/1472-6963-12-451,PMC3544629,23217103,CC BY,"BACKGROUND: Pediatric LRTI hospitalizations are a significant burden on patients, families, and healthcare systems. This study determined the burden of pediatric LRTIs on hospital settings in British Columbia and the benefits of prevention strategies as they relate to healthcare resource demand. METHODS: LRTI inpatient episodes for patients <19 years of age during 2008–2010 were extracted from the BC Discharge Abstract Database. The annual number of acute care beds required to treat pediatric LRTIs was estimated. Sub-analyses determined the burden due to infants <1 year of age and high-risk infants. Population projections were used to forecast LRTI hospitalizations and the effectiveness of public health initiatives to reduce the incidence of LRTIs to 2020 and 2030. RESULTS: During 2008–2010, LRTI as the primary diagnosis accounted for 32.0 and 75.9% hospitalizations for diseases of the respiratory system in children <19 years of age and infants <1 year of age, respectively. Infants <1 year of age accounted for 47 and 77% hospitalizations due to pediatric LRTIs and pediatric LRTI hospitalizations specifically due to respiratory syncytial virus (RSV), respectively. The average length of stay was 3.1 days for otherwise healthy infants <1 year of age and 9.1 days for high-risk infants (P <0.0001). 73.1% pediatric LRTI hospitalizations occurred between November and April. Over the study timeframe, 19.6 acute care beds were required on average to care for pediatric LRTIs which increased to 64.0 beds at the peak of LRTI hospitalizations. Increases in LRTI bed-days of 5.5 and 16.2% among <19 year olds by 2020 and 2030, respectively, were predicted. Implementation of appropriate prevention strategies could cause 307 and 338 less LRTI hospitalizations in <19 year olds in 2020 and 2030, respectively. CONCLUSION: Pediatric LRTI hospitalizations require significant use of acute care infrastructure particularly between November and April. Population projections show the burden may increase in the next 20 years, but implementation of effective public health prevention strategies may contribute to reducing the acute care demand and to supporting efforts for overall pediatric healthcare sustainability.",2012 Dec 8,"['Santibanez, Pablo', 'Gooch, Katherine', 'Vo, Pamela', 'Lorimer, Michelle', 'Sandino, Yurik']",BMC Health Serv Res,,,True
a3d1def9eb134591e3d0b38dc1c1330745da34a0,PMC,Comparison of the geographical distribution of feline immunodeficiency virus and feline leukemia virus infections in the United States of America (2000–2011),http://dx.doi.org/10.1186/1746-6148-9-2,PMC3544736,23289366,CC BY,"BACKGROUND: Although feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) have similar risk factors and control measures, infection rates have been speculated to vary in geographic distribution over North America. Since both infections are endemic in North America, it was assumed as a working hypothesis that their geographic distributions were similar. Hence, the purpose of this exploratory analysis was to investigate the comparative geographical distribution of both viral infections. Counts of FIV (n=17,108) and FeLV (n=30,017) positive serology results (FIV antibody and FeLV ELISA) were obtained for 48 contiguous states and District of Columbia of the United States of America (US) from the IDEXX Laboratories website. The proportional morbidity ratio of FIV to FeLV infection was estimated for each administrative region and its geographic distribution pattern was visualized by a choropleth map. Statistical evidence of an excess in the proportional morbidity ratio from unity was assessed using the spatial scan test under the normal probability model. RESULTS: This study revealed distinct spatial distribution patterns in the proportional morbidity ratio suggesting the presence of one or more relevant and geographically varying risk factors. The disease map indicates that there is a higher prevalence of FIV infections in the southern and eastern US compared to FeLV. In contrast, FeLV infections were observed to be more frequent in the western US compared to FIV. The respective excess in proportional morbidity ratio was significant with respect to the spatial scan test (p < 0.05). CONCLUSIONS: The observed variability in the geographical distribution of the proportional morbidity ratio of FIV to FeLV may be related to the presence of an additional or unique, but yet unknown, spatial risk factor. Putative factors may be geographic variations in specific virus strains and rate of vaccination. Knowledge of these factors and the geographical distributions of these infections can inform recommendations for testing, management and prevention. However, further studies are required to investigate the potential association of these factors with FIV and FeLV.",2013 Jan 5,"['Chhetri, Bimal K', 'Berke, Olaf', 'Pearl, David L', 'Bienzle, Dorothee']",BMC Vet Res,,,True
59a11e8976b666ba112da942d7ba7c698d06a9e8,PMC,Mutations in the Fusion Protein Cleavage Site of Avian Paramyxovirus Serotype 4 Confer Increased Replication and Syncytium Formation In Vitro but Not Increased Replication and Pathogenicity in Chickens and Ducks,http://dx.doi.org/10.1371/journal.pone.0050598,PMC3544850,23341874,CC0,"To evaluate the role of the F protein cleavage site in the replication and pathogenicity of avian paramyxoviruses (APMVs), we constructed a reverse genetics system for recovery of infectious recombinant APMV-4 from cloned cDNA. The recovered recombinant APMV-4 resembled the biological virus in growth characteristics in vitro and in pathogenicity in vivo. The F cleavage site sequence of APMV-4 (DIQPR↓F) contains a single basic amino acid, at the -1 position. Six mutant APMV-4 viruses were recovered in which the F protein cleavage site was mutated to contain increased numbers of basic amino acids or to mimic the naturally occurring cleavage sites of several paramyxoviruses, including neurovirulent and avirulent strains of NDV. The presence of a glutamine residue at the -3 position was found to be important for mutant virus recovery. In addition, cleavage sites containing the furin protease motif conferred increased replication and syncytium formation in vitro. However, analysis of viral pathogenicity in 9-day-old embryonated chicken eggs, 1-day-old and 2-week-old chickens, and 3-week-old ducks showed that none the F protein cleavage site mutations altered the replication, tropism, and pathogenicity of APMV-4, and no significant differences were observed among the parental and mutant APMV-4 viruses in vivo. Although parental and mutant viruses replicated somewhat better in ducks than in chickens, they all were highly restricted and avirulent in both species. These results suggested that the cleavage site sequence of the F protein is not a limiting determinant of APMV-4 pathogenicity in chickens and ducks.",2013 Jan 14,"['Kim, Shin-Hee', 'Xiao, Sa', 'Shive, Heather', 'Collins, Peter L.', 'Samal, Siba K.']",PLoS One,,,True
fdd06eeb020a963754fee36852a5918a93f7856d,PMC,"Initial Antihypertensive Prescription and Switching: A 5 Year Cohort Study from 250,851 Patients",http://dx.doi.org/10.1371/journal.pone.0053625,PMC3544913,23341959,CC BY,"PURPOSE: Adverse effects of antihypertensive therapy incur substantial cost. We evaluated whether any major classes of antihypertensive drugs were significantly associated with switching as a proxy measure of medication side effects in a large Chinese population in Hong Kong. METHODS: From a clinical database, all adult patients newly prescribed an antihypertensive mono-therapy in Hong Kong between the years 2001–2003 and 2005 were included. Those who paid only one visit, died or stayed in the cohort for <180 days after the prescription, or prescribed more than one antihypertensive agent were excluded. The factors associated with switching at 180 days were evaluated by multivariate regression analyses. Age, gender, payment status, service type, district of residence, drug class, systolic and diastolic blood pressure levels were predictor variables. RESULTS: From 250,851 subjects, 159,813 patients were eligible. A total of 6,163 (3.9%) switched their medications within 180 days. Patients prescribed thiazide diuretics had the highest switching rate (5.6%), followed by ACEIs (4.5%), CCBs (4.4%) and beta-blockers (3.2%). When compared with ACEIs, patients on thiazide diuretics were significantly more likely to be switchers (adjusted odds ratio [AOR] 1.49, 95% C.I. 1.31–1.69, p<0.001), whilst patients prescribed CCBs and beta-blockers were similarly likely to have switching. Following these patients up for 5 years showed that thiazide had the most marked increase in switching rate. CONCLUSIONS: The higher rates of switching among thiazide diuretics in this study might raise a probably greater incidence of their adverse effects in this Chinese population, yet other factors might also influence switching rates. Patients prescribed thiazide diuretics for longer term should be observed for their intolerability.",2013 Jan 14,"['Wong, Martin C. S.', 'Tam, Wilson W. S.', 'Cheung, Clement S. K.', 'Tong, Ellen L. H.', 'Sek, Antonio C. H.', 'John, George', 'Cheung, N. T.', 'Yan, Bryan P. Y.', 'Yu, C. M.', 'Leeder, Stephen', 'Griffiths, Sian']",PLoS One,,,True
c59d6e789176b928523129adb96ca495720a3b4a,PMC,Enhanced CD8 T-cell anti-viral function and clinical disease in B7-H1-deficient mice requires CD4 T cells during encephalomyelitis,http://dx.doi.org/10.1186/1742-2094-9-269,PMC3545890,23237504,CC BY,"BACKGROUND: Anti-viral CD8 T-cell activity is enhanced and prolonged by CD4 T-cell-mediated help, but negatively regulated by inhibitory B7-H1 interactions. During viral encephalomyelitis, the absence of CD4 T cells decreases CD8 T cell activity and impedes viral control in the central nervous system (CNS). By contrast, the absence of B7-H1 enhances CD8 T-cell function and accelerates viral control, but increases morbidity. However, the relative contribution of CD4 T cells to CD8 function in the CNS, in the absence of B7-H1, remains unclear. METHODS: Wild-type (WT) and B7-H1(−/−) mice were infected with a gliatropic coronavirus and CD4 T cells depleted to specifically block T helper function in the CNS. Flow cytometry and gene expression analysis of purified T-cell populations from lymph nodes and the CNS was used to directly monitor ex vivo T-cell effector function. The biological affects of altered T-cell responses were evaluated by analysis of viral control and spinal-cord pathology. RESULTS: Increased anti-viral activity by CD8 T cells in the CNS of B7-H1(−/−) mice was lost upon depletion of CD4 T cells; however, despite concomitant loss of viral control, the clinical disease was less severe. CD4 depletion in B7-H1(−/−) mice also decreased inducible nitric oxide synthase expression by microglia and macrophages, consistent with decreased microglia/macrophage activation and reduced interferon (IFN)-γ. Enhanced production of IFN-γ, interleukin (IL)-10 and IL-21 mRNA was seen in CD4 T cells from infected B7-H1(−/−) compared with WT mice, suggesting that over-activated CD4 T cells primarily contribute to the increased pathology. CONCLUSIONS: The local requirement of CD4 T-cell help for CD8 T-cell function is not overcome if B7-H1 inhibitory signals are lost. Moreover, the increased effector activity by CD8 T cells in the CNS of B7-H1(−/−) mice is attributable not only to the absence of B7-H1 upregulation on major histocompatibility complex class I-presenting resident target cells, but also to enhanced local CD4 T-cell function. B7-H1-mediated restraint of CD4 T-cell activity is thus crucial to dampen both CD8 T-cell function and microglia/macrophage activation, thereby providing protection from T-cell-mediated bystander damage.",2012 Dec 14,"['Phares, Timothy W', 'Stohlman, Stephen A', 'Hinton, David R', 'Bergmann, Cornelia C']",J Neuroinflammation,,,True
3acc047295ee11b02f13aac787a12fe114d58558,PMC,Identification of a novel Getah virus by Virus-Discovery-cDNA random amplified polymorphic DNA (RAPD),http://dx.doi.org/10.1186/1471-2180-12-305,PMC3547691,23268691,CC BY,"BACKGROUND: The identification of new virus strains is important for the study of infectious disease, but current (or existing) molecular biology methods are limited since the target sequence must be known to design genome-specific PCR primers. Thus, we developed a new method for the discovery of unknown viruses based on the cDNA - random amplified polymorphic DNA (cDNA-RAPD) technique. Getah virus, belonging to the family Togaviridae in the genus Alphavirus, is a mosquito-borne enveloped RNA virus that was identified using the Virus-Discovery-cDNA RAPD (VIDISCR) method. RESULTS: A novel Getah virus was identified by VIDISCR from suckling mice exposed to mosquitoes (Aedes albopictus) collected in Yunnan Province, China. The non-structural protein gene, nsP3, the structural protein gene, the capsid protein gene, and the 3'-untranslated region (UTR) of the novel Getah virus isolate were cloned and sequenced. Nucleotide sequence identities of each gene were determined to be 97.1–99.3%, 94.9–99.4%, and 93.6–99.9%, respectively, when compared with the genomes of 10 other representative strains of Getah virus. CONCLUSIONS: The VIDISCR method was able to identify known virus isolates and a novel isolate of Getah virus from infected mice. Phylogenetic analysis indicated that the YN08 isolate was more closely related to the Hebei HB0234 strain than the YN0540 strain, and more genetically distinct from the MM2021 Malaysia primitive strain.",2012 Dec 27,"['Hu, Tingsong', 'Zheng, Ying', 'Zhang, Yan', 'Li, Gangshan', 'Qiu, Wei', 'Yu, Jing', 'Cui, Qinghua', 'Wang, Yiyin', 'Zhang, Chaoxiong', 'Zhou, Xiaofang', 'Feng, Ziliang', 'Zhou, Weiguo', 'Fan, Quanshui', 'Zhang, Fuqiang']",BMC Microbiol,,,True
29da5f5d00af5c47f9b3a0a49d561f8caffb0cf3,PMC,Anti-rotaviral effects of Glycyrrhiza uralensis extract in piglets with rotavirus diarrhea,http://dx.doi.org/10.1186/1743-422X-9-310,PMC3547719,23244491,CC BY,"BACKGROUND: Since rotavirus is one of the leading pathogens that cause severe gastroenteritis and represents a serious threat to human and animal health, researchers have been searching for cheap, safe, and effective anti-rotaviral drugs. There is a widespread of interest in using natural products as antiviral agents, and among them, licorice derived from Glycyrrhiza spp. has exerted antiviral properties against several viruses. In this study, anti-rotaviral efficacy of Glycyrrhiza uralensis extract (GUE) as an effective and cheaper remedy without side-effects was evaluated in colostrums-deprived piglets after induction of rotavirus diarrhea. METHODS: Colostrums-deprived piglets were inoculated with porcine rotavirus K85 (G5P[7]) strain. On the onset of diarrhea, piglets were treated with different concentration of GUE. To evaluate the antiviral efficacy of GUE, fecal consistency score, fecal virus shedding and histological changes of the small intestine, mRNA expression levels of inflammation-related cytokines (IL8, IL10, IFN-β, IFN-γ and TNF-α), signaling molecules (p38 and JNK), and transcription factor (NFκB) in the small intestine and spleen were determined. RESULTS: Among the dosages (100-400 mg/ml) administrated to animals, 400 mg/ml of GUE cured diarrhea, and markedly improved small intestinal lesion score and fecal virus shedding. mRNA expression levels of inflammation-related cytokines (IL8, IL10, IFN-β, IFN-γ and TNF-α), signaling molecules (p38 and JNK), and transcription factor (NFκB) in the small intestine and spleen were markedly increased in animals with RVA-induced diarrhea, but dose- dependently decreased in GUE treated animals after RVA-induced diarrhea. CONCLUSIONS: GUE cures rotaviral enteritis by coordinating antiviral and anti-inflammatory effects. Therapy of this herbal medicine can be a viable medication for curing rotaviral enteritis in animals and humans.",2012 Dec 18,"['Alfajaro, Mia Madel', 'Kim, Hyun-Jeong', 'Park, Jun-Gyu', 'Ryu, Eun-Hye', 'Kim, Ji-Yun', 'Jeong, Young-Ju', 'Kim, Deok-Song', 'Hosmillo, Myra', 'Son, Kyu-Yeol', 'Lee, Ju-Hwan', 'Kwon, Hyung-Jun', 'Ryu, Young Bae', 'Park, Su-Jin', 'Park, Sang-Ik', 'Lee, Woo Song', 'Cho, Kyoung-Oh']",Virol J,,,True
a0d73d877a6bcede67ac884d7e5ada5dd3eb810c,PMC,The Immunosuppressive Agent Mizoribine Monophosphate Is an Inhibitor of the Human RNA Capping Enzyme,http://dx.doi.org/10.1371/journal.pone.0054621,PMC3547949,23349942,CC BY,"Mizoribine monophosphate (MZP) is a specific inhibitor of the cellular inosine-5′-monophosphate dehydrogenase (IMPDH), the enzyme catalyzing the rate-limiting step of de novo guanine nucleotide biosynthesis. MZP is a highly potent antagonistic inhibitor of IMPDH that blocks the proliferation of T and B lymphocytes that use the de novo pathway of guanine nucleotide synthesis almost exclusively. In the present study, we investigated the ability of MZP to directly inhibit the human RNA capping enzyme (HCE), a protein harboring both RNA 5′-triphosphatase and RNA guanylyltransferase activities. HCE is involved in the synthesis of the cap structure found at the 5′ end of eukaryotic mRNAs, which is critical for the splicing of the cap-proximal intron, the transport of mRNAs from the nucleus to the cytoplasm, and for both the stability and translation of mRNAs. Our biochemical studies provide the first insight that MZP can inhibit the formation of the RNA cap structure catalyzed by HCE. In the presence of MZP, the RNA 5′-triphosphatase activity appears to be relatively unaffected while the RNA guanylyltransferase activity is inhibited, indicating that the RNA guanylyltransferase activity is the main target of MZP inhibition. Kinetic studies reveal that MZP is a non-competitive inhibitor that likely targets an allosteric site on HCE. Mizoribine also impairs mRNA capping in living cells, which could account for the global mechanism of action of this therapeutic agent. Together, our study clearly demonstrates that mizoribine monophosphate inhibits the human RNA guanylyltransferase in vitro and impair mRNA capping in cellulo.",2013 Jan 17,"['Picard-Jean, Frédéric', 'Bougie, Isabelle', 'Shuto, Satoshi', 'Bisaillon, Martin']",PLoS One,,,True
6ed77e5ebba3c0f0b10c6e0af3e8df28b57335e6,PMC,Automated degenerate PCR primer design for high-throughput sequencing improves efficiency of viral sequencing,http://dx.doi.org/10.1186/1743-422X-9-261,PMC3548747,23131097,CC BY,"BACKGROUND: In a high-throughput environment, to PCR amplify and sequence a large set of viral isolates from populations that are potentially heterogeneous and continuously evolving, the use of degenerate PCR primers is an important strategy. Degenerate primers allow for the PCR amplification of a wider range of viral isolates with only one set of pre-mixed primers, thus increasing amplification success rates and minimizing the necessity for genome finishing activities. To successfully select a large set of degenerate PCR primers necessary to tile across an entire viral genome and maximize their success, this process is best performed computationally. RESULTS: We have developed a fully automated degenerate PCR primer design system that plays a key role in the J. Craig Venter Institute’s (JCVI) high-throughput viral sequencing pipeline. A consensus viral genome, or a set of consensus segment sequences in the case of a segmented virus, is specified using IUPAC ambiguity codes in the consensus template sequence to represent the allelic diversity of the target population. PCR primer pairs are then selected computationally to produce a minimal amplicon set capable of tiling across the full length of the specified target region. As part of the tiling process, primer pairs are computationally screened to meet the criteria for successful PCR with one of two described amplification protocols. The actual sequencing success rates for designed primers for measles virus, mumps virus, human parainfluenza virus 1 and 3, human respiratory syncytial virus A and B and human metapneumovirus are described, where >90% of designed primer pairs were able to consistently successfully amplify >75% of the isolates. CONCLUSIONS: Augmenting our previously developed and published JCVI Primer Design Pipeline, we achieved similarly high sequencing success rates with only minor software modifications. The recommended methodology for the construction of the consensus sequence that encapsulates the allelic variation of the targeted population and is a key step prior to designing degenerate primers is also formally described.",2012 Nov 6,"['Li, Kelvin', 'Shrivastava, Susmita', 'Brownley, Anushka', 'Katzel, Dan', 'Bera, Jayati', 'Nguyen, Anh Thu', 'Thovarai, Vishal', 'Halpin, Rebecca', 'Stockwell, Timothy B']",Virol J,,,True
71d134916c750fb6f875d3936a957b27a5df72bc,PMC,Debate around infection-dependent hemophagocytic syndrome in paediatrics,http://dx.doi.org/10.1186/1471-2334-13-15,PMC3549728,23324497,CC BY,"BACKGROUND: Hemophagocytic syndrome (HPS) is clinically defined as a combination of fever, liver dysfunction, coagulation abnormalities, pancytopenia, progressive macrophage proliferation throughout the reticuloendothelial system, and cytokine over-production, and may be primary or secondary to infectious, auto-immune, and tumoral diseases. The most consistent association is with viral infections but, as it is still debated whether any micro-organisms are involved in its pathogenesis, we critically appraised the literature concerning HPS and its relationship with infections. DISCUSSION: Infection-dependent HPS has been widely observed, but there are no data concerning its incidence in children. A better understanding of the pathophysiology of HPS may clarify the interactions between the immune system and the variously implicated potential infectious agents. Epstein-Barr virus (EBV) infection has been prominently associated with HPS, with clonal proliferation and the hyperactivation of EBV-infected T cells. However, a number of other viral, bacterial, fungal, and parasitic infections have been reported in association with HPS. In the case of low-risk HPS, corticosteroids and/or intravenous immunoglobulin or cyclosporine A may be sufficient to control the biological process, but etoposide is recommended as a means of reversing infection-dependent lymphohistiocytic dysregulation in high-risk cases. SUMMARY: HPS is a potential complication of various infections. A polymerase chain reaction search for infectious agents including EBV, cytomegalovirus and Leishmania is recommended in clinical settings characterised by non-remitting fever, organomegaly, cytopenia and hyperferritinemia.",2013 Jan 16,"['Ansuini, Valentina', 'Rigante, Donato', 'Esposito, Susanna']",BMC Infect Dis,,,True
54cbbaf44335fdc1995cb19e5a08779929fd0966,PMC,HIV-1 Fusion Is Blocked through Binding of GB Virus C E2D Peptides to the HIV-1 gp41 Disulfide Loop,http://dx.doi.org/10.1371/journal.pone.0054452,PMC3551756,23349893,CC BY,"A strategy for antiviral drug discovery is the elucidation and imitation of viral interference mechanisms. HIV-1 patients benefit from a coinfection with GB Virus C (GBV-C), since HIV-positive individuals with long-term GBV-C viraemia show better survival rates than HIV-1 patients without persisting GBV-C. A direct influence of GBV-C on HIV-1 replication has been shown in coinfection experiments. GBV-C is a human non-pathogenic member of the flaviviridae family that can replicate in T and B cells. Therefore, GBV-C shares partly the same ecological niche with HIV-1. In earlier work we have demonstrated that recombinant glycoprotein E2 of GBV-C and peptides derived from the E2 N-terminus interfere with HIV entry. In this study we investigated the underlying mechanism. Performing a virus-cell fusion assay and temperature-arrested HIV-infection kinetics, we provide evidence that the HIV-inhibitory E2 peptides interfere with late HIV-1 entry steps after the engagement of gp120 with CD4 receptor and coreceptor. Binding and competition experiments revealed that the N-terminal E2 peptides bind to the disulfide loop region of HIV-1 transmembrane protein gp41. In conjunction with computational analyses, we identified sequence similarities between the N-termini of GBV-C E2 and the HIV-1 glycoprotein gp120. This similarity appears to enable the GBV-C E2 N-terminus to interact with the HIV-1 gp41 disulfide loop, a crucial domain involved in the gp120-gp41 interface. Furthermore, the results of the present study provide initial proof of concept that peptides targeted to the gp41 disulfide loop are able to inhibit HIV fusion and should inspire the development of this new class of HIV-1 entry inhibitors.",2013 Jan 22,"['Eissmann, Kristin', 'Mueller, Sebastian', 'Sticht, Heinrich', 'Jung, Susan', 'Zou, Peng', 'Jiang, Shibo', 'Gross, Andrea', 'Eichler, Jutta', 'Fleckenstein, Bernhard', 'Reil, Heide']",PLoS One,,,True
de22df7c68cc8f64265c0a26ef9f2acd53520ef6,PMC,Chemokine CXCL14 is associated with prognosis in patients with colorectal carcinoma after curative resection,http://dx.doi.org/10.1186/1479-5876-11-6,PMC3551837,23294544,CC BY,"BACKGROUND: The chemokine CXCL14 has been reported to play an important role in the progression of many malignancies such as breast cancer and papillary thyroid carcinoma, but the role of CXCL14 in colorectal carcinoma (CRC) remains to be established. The purpose of this study was to investigate the expression pattern and significance of CXCL14 in CRC progression. METHOD: 265 colorectal carcinoma specimens and 129 matched adjacent normal colorectal mucosa specimens were collected. Expression of CXCL14 in clinical samples was examined by immunostaining. The effect of CXCL14 on colorectal carcinoma cell proliferation was measured by MTT assay, BrdU incorporation assay and colony formation assay. The impact of CXCL14 on migration and invasion of colorectal carcinoma cells was determined by transwell assay and Matrigel invasion assay, respectively. RESULTS: CXCL14 expression was significantly up-regulated in tumor tissues compared with adjacent nontumorous mucosa tissues (P < 0.001). Tumoral CXCL14 expression levels were significantly correlated with TNM (Tumor-node-metastasis) stage, histodifferentiation, and tumor size. In multivariate Cox regression analysis, high CXCL14 expression in tumor specimens (n = 91) from stage I/II patients was associated with increased risk for disease recurrence (risk ratio, 2.92; 95% CI, 1.15-7.40; P = 0.024). Elevated CXCL14 expression in tumor specimens (n = 135) from stage III/IV patients correlated with worse overall survival (risk ratio, 3.087; 95% CI, 1.866-5.107; P < 0.001). Functional studies demonstrated that enforced expression of CXCL14 in SW620 colorectal carcinoma cells resulted in more aggressive phenotypes. In contrast, knockdown of CXCL14 expression could mitigate the proliferative, migratory and invasive potential of HCT116 colorectal carcinoma cells. CONCLUSION: Taken together, CXCL14 might be a potential novel prognostic factor to predict the disease recurrence and overall survival and could be a potential target of postoperative adjuvant therapy in CRC patients.",2013 Jan 7,"['Zeng, Jun', 'Yang, Xudan', 'Cheng, Lin', 'Liu, Rui', 'Lei, Yunlong', 'Dong, Dandan', 'Li, Fanghua', 'Lau, Quek Choon', 'Deng, Longfei', 'Nice, Edouard C', 'Xie, Ke', 'Huang, Canhua']",J Transl Med,,,True
406aad9b3f74f619a1aac3f29ad531b28fb7c37e,PMC,Use of Toll-Like Receptor 3 Agonists Against Respiratory Viral Infections,http://dx.doi.org/10.2174/187152111800194434,PMC3552307,,CC BY,"Respiratory RNA viruses are constantly evolving, thus requiring development of additional prophylactic and therapeutic strategies. Harnessing the innate immune system to non-specifically respond to viral infection has the advantage of being able to circumvent viral mutations that render the virus resistant to a particular therapeutic agent. Viruses are recognized by various cellular receptors, including Toll-like receptor (TLR) 3 which recognizes double-stranded (ds)RNA produced during the viral replication cycle. TLR3 agonists include synthetic dsRNA such as poly (IC), poly (ICLC) and poly (AU). These agents have been evaluated and found to be effective against a number of viral agents. One major limitation has been the toxicity associated with administration of these drugs. Significant time and effort have been spent to develop alternatives/modifications that will minimize these adverse effects. This review will focus on the TLR3 agonist, poly (IC)/(ICLC) with respect to its use in treatment/prevention of respiratory viral infections.",2011 Oct,"['Christopher, ME', 'Wong, JP']",Antiinflamm Antiallergy Agents Med Chem,,,True
d0a7af58aa5e272f1c7aef4e6908dd3059d9173e,PMC,Proteasome inhibition in cancer is associated with enhanced tumor targeting by the adeno‐associated virus/phage,http://dx.doi.org/10.1016/j.molonc.2012.08.001,PMC3553581,22951279,CC BY,"Bacteriophage (phage), which are viruses that infect bacteria only, have shown promise as vehicles for targeted cancer gene therapy, albeit with poor efficiency. Recently, we generated an improved version of phage vectors by incorporating cis genetic elements of adeno‐associated virus (AAV). This novel AAV/phage hybrid (AAVP) efficiently delivered systemically administered therapeutic genes to various tumor targets by displaying an integrin tumor‐targeting ligand on the phage capsid. However, inherent limitations in bacteriophage mean that these AAVP vectors still need to be improved. One of the limitations of AAVP in mammalian cells may be its susceptibility to proteasomal degradation. The proteasome is upregulated in cancer and it is known that it constitutes a barrier to gene delivery by certain eukaryotic viruses. We report here that inhibition of proteasome improved targeted reporter gene delivery by AAVP in cancer cells in vitro and in tumors in vivo after intravenous vector administration to tumor‐bearing mice. We also show enhanced targeted tumor cell killing by AAVP upon proteasome inhibition. The AAVP particles persisted significantly in cancer cells in vitro and in tumors in vivo after systemic administration, and accumulated polyubiquitinated coat proteins. Our results suggest that the proteasome is indeed a barrier to tumor targeting by AAVP and indicate that a combination of proteasome‐inhibiting drugs and AAVP should be considered for clinical anticancer therapy.",2013 Feb 21,"['Przystal, Justyna M.', 'Umukoro, Eloho', 'Stoneham, Charlotte A.', 'Yata, Teerapong', ""O'Neill, Kevin"", 'Syed, Nelofer', 'Hajitou, Amin']",Mol Oncol,,,True
21083480591a0f89c6c6a1ee575c79ef9eeaeb75,PMC,"C-reactive protein, haptoglobin, serum amyloid A and pig major acute phase protein response in pigs simultaneously infected with H1N1 swine influenza virus and Pasteurella multocida",http://dx.doi.org/10.1186/1746-6148-9-14,PMC3554491,23332090,CC BY,"BACKGROUND: Swine influenza (SI) is an acute respiratory disease caused by swine influenza virus (SIV). Swine influenza is generally characterized by acute onset of fever and respiratory symptoms. The most frequent complications of influenza are secondary bacterial pneumonia. The objective of this work was to study the acute phase proteins (APP) responses after coinfection of piglets with H1N1 swine influenza virus (SwH1N1) and Pasteurella multocida (Pm) in order to identify whether the individual APP response correlate with disease severity and whether APP could be used as markers of the health status of coinfected pigs. RESULTS: In all coinfected pigs clinical sings, including fever, coughing and dyspnea, were seen. Viral shedding was observed from 2 to 7 dpi. The mean level of antibodies against Pm dermonecrotoxin in infected piglets increase significantly from 7 dpi. Anti-SwH1N1 antibodies in the serum were detected from 7 dpi. The concentration of C-reactive protein (CRP) increased significantly at 1 dpi as compared to control pigs, and remained significantly higher to 3 dpi. Level of serum amyloid A (SAA) was significantly higher from 2 to 3 dpi. Haptoglobin (Hp) was significantly elevated from 3 dpi to the end of study, while pig major acute phase protein (Pig-MAP) from 3 to 7 dpi. The concentrations of CRP, Hp and SAA significantly increased before specific antibodies were detected. Positive correlations were found between serum concentration of Hp and SAA and lung scores, and between clinical score and concentrations of Pig-MAP and SAA. CONCLUSIONS: The results of current study confirmed that monitoring of APP may revealed ongoing infection, and in this way may be useful in selecting clinically healthy pigs (i.e. before integration into an uninfected herd). Present results corroborated our previous findings that SAA could be a potentially useful indicator in experimental infection studies (e.g. vaccine efficiency investigations) or as a marker for disease severity, because of correlation observed between its concentration in serum and disease severity (lung scores, clinical scores).",2013 Jan 18,"['Pomorska-Mól, Małgorzata', 'Markowska-Daniel, Iwona', 'Kwit, Krzysztof', 'Stępniewska, Katarzyna', 'Pejsak, Zygmunt']",BMC Vet Res,,,True
1ca045bd7724943ce8c268353153bd522358625d,PMC,Positional Bias of MHC Class I Restricted T-Cell Epitopes in Viral Antigens Is Likely due to a Bias in Conservation,http://dx.doi.org/10.1371/journal.pcbi.1002884,PMC3554532,23357871,CC0,"The immune system rapidly responds to intracellular infections by detecting MHC class I restricted T-cell epitopes presented on infected cells. It was originally thought that viral peptides are liberated during constitutive protein turnover, but this conflicts with the observation that viral epitopes are detected within minutes of their synthesis even when their source proteins exhibit half-lives of days. The DRiPs hypothesis proposes that epitopes derive from Defective Ribosomal Products (DRiPs), rather than degradation of mature protein products. One potential source of DRiPs is premature translation termination. If this is a major source of DRiPs, this should be reflected in positional bias towards the N-terminus. By contrast, if downstream initiation is a major source of DRiPs, there should be positional bias towards the C-terminus. Here, we systematically assessed positional bias of epitopes in viral antigens, exploiting the large set of data available in the Immune Epitope Database and Analysis Resource. We show a statistically significant degree of positional skewing among epitopes; epitopes from both ends of antigens tend to be under-represented. Centric-skewing correlates with a bias towards class I binding peptides being over-represented in the middle, in parallel with a higher degree of evolutionary conservation.",2013 Jan 24,"['Kim, Yohan', 'Yewdell, Jonathan W.', 'Sette, Alessandro', 'Peters, Bjoern']",PLoS Comput Biol,,,True
5e11e3105842cf7cedf10e26bff170a52c23cf00,PMC,IFITM Proteins Restrict Viral Membrane Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1003124,PMC3554583,23358889,CC BY,"The interferon-inducible transmembrane (IFITM) protein family represents a new class of cellular restriction factors that block early stages of viral replication; the underlying mechanism is currently not known. Here we provide evidence that IFITM proteins restrict membrane fusion induced by representatives of all three classes of viral membrane fusion proteins. IFITM1 profoundly suppressed syncytia formation and cell-cell fusion induced by almost all viral fusion proteins examined; IFITM2 and IFITM3 also strongly inhibited their fusion, with efficiency somewhat dependent on cell types. Furthermore, treatment of cells with IFN also markedly inhibited viral membrane fusion and entry. By using the Jaagsiekte sheep retrovirus envelope and influenza A virus hemagglutinin as models for study, we showed that IFITM-mediated restriction on membrane fusion is not at the steps of receptor- and/or low pH-mediated triggering; instead, the creation of hemifusion was essentially blocked by IFITMs. Chlorpromazine (CPZ), a chemical known to promote the transition from hemifusion to full fusion, was unable to rescue the IFITM-mediated restriction on fusion. In contrast, oleic acid (OA), a lipid analog that generates negative spontaneous curvature and thereby promotes hemifusion, virtually overcame the restriction. To explore the possible effect of IFITM proteins on membrane molecular order and fluidity, we performed fluorescence labeling with Laurdan, in conjunction with two-photon laser scanning and fluorescence-lifetime imaging microscopy (FLIM). We observed that the generalized polarizations (GPs) and fluorescence lifetimes of cell membranes expressing IFITM proteins were greatly enhanced, indicating higher molecularly ordered and less fluidized membranes. Collectively, our data demonstrated that IFITM proteins suppress viral membrane fusion before the creation of hemifusion, and suggested that they may do so by reducing membrane fluidity and conferring a positive spontaneous curvature in the outer leaflets of cell membranes. Our study provides novel insight into the understanding of how IFITM protein family restricts viral membrane fusion and infection.",2013 Jan 24,"['Li, Kun', 'Markosyan, Ruben M.', 'Zheng, Yi-Min', 'Golfetto, Ottavia', 'Bungart, Brittani', 'Li, Minghua', 'Ding, Shilei', 'He, Yuxian', 'Liang, Chen', 'Lee, James C.', 'Gratton, Enrico', 'Cohen, Fredric S.', 'Liu, Shan-Lu']",PLoS Pathog,,,True
1f4ec41f723e758522faa99829a52f00ea45a9e2,PMC,Aerobiology and Its Role in the Transmission of Infectious Diseases,http://dx.doi.org/10.1155/2013/493960,PMC3556854,23365758,CC BY,"Aerobiology plays a fundamental role in the transmission of infectious diseases. As infectious disease and infection control practitioners continue employing contemporary techniques (e.g., computational fluid dynamics to study particle flow, polymerase chain reaction methodologies to quantify particle concentrations in various settings, and epidemiology to track the spread of disease), the central variables affecting the airborne transmission of pathogens are becoming better known. This paper reviews many of these aerobiological variables (e.g., particle size, particle type, the duration that particles can remain airborne, the distance that particles can travel, and meteorological and environmental factors), as well as the common origins of these infectious particles. We then review several real-world settings with known difficulties controlling the airborne transmission of infectious particles (e.g., office buildings, healthcare facilities, and commercial airplanes), while detailing the respective measures each of these industries is undertaking in its effort to ameliorate the transmission of airborne infectious diseases.",2013 Jan 13,"['Fernstrom, Aaron', 'Goldblatt, Michael']",J Pathog,,,True
aac395d967bf4ce6affb506eb9cf5f1bf853e69f,PMC,Coronavirus infections in hospitalized pediatric patients with acute respiratory tract disease,http://dx.doi.org/10.1186/1471-2334-12-365,PMC3557153,23256846,CC BY,"BACKGROUND: Acute viral respiratory infections are an important cause of morbidity and mortality in humans worldwide. The etiological backgrounds of these infections remain unconfirmed in most clinical cases. The aim of this study was to estimate the prevalence of human coronavirus infections in a series of children hospitalized with symptoms of acute respiratory tract disease in a one-year period in Slovenia. METHODS: The 664 specimens from 592 children under six years of age hospitalized at the University Children’s Hospital in Ljubljana were sent for the routine laboratory detection of respiratory viruses. Respiratory viruses were detected with a direct immunofluorescence assay and human coronaviruses were detected with a modified real-time RT–PCR. RESULTS: HCoV RNA was detected in 40 (6%, 95% CI: 4.3%–8.1%) of 664 samples. Of these specimens, 21/40 (52.5%) were identified as species HKU1, 7/40 (17.5%) as OC43, 6/40 (15%) as 229E, and 6/40 (15%) as NL63. Infection with HCoV occurred as a coinfection with one or more other viruses in most samples (70%). Of the HCoV-positive children, 70.3% had lower respiratory tract infections. CONCLUSION: The results of our study show that HCoV are frequently detected human pathogens, often associated with other respiratory viruses and acute respiratory tract infections in hospitalized children. An association between age and the viral load was found. The highest viral load was detected in children approximately 10 months of age.",2012 Dec 20,"['Jevšnik, Monika', 'Uršič, Tina', 'Žigon, Nina', 'Lusa, Lara', 'Krivec, Uroš', 'Petrovec, Miroslav']",BMC Infect Dis,,,True
884b19f49da8930b2222b5669f387ed974d1f3f3,PMC,Mekong Basin Disease Surveillance (MBDS): A Trust-Based Network,http://dx.doi.org/10.3402/ehtj.v6i0.19944,PMC3557908,23362411,CC BY,"The Mekong Basin Disease Surveillance (MBDS) network was formally established in 2001 through a Memorandum of Understanding signed by six Ministers of Health of the countries in the Greater Mekong sub-region: Cambodia, China (Yunnan and Guangxi), Lao PDR, Myanmar, Thailand and Vietnam. The main areas of focus of the network are to: i) improve cross-border infectious disease outbreak investigation and response by sharing surveillance data and best practices in disease recognition and reporting, and by jointly responding to outbreaks; ii) develop expertise in epidemiological surveillance across the countries; and iii) enhance communication between the countries. Comprised of senior health officials, epidemiologists, health practitioners, and other professionals, the MBDS has grown and matured over the years into an entity based on mutual trust that can be sustained into the future. Other regions have started emulating the network's pioneering work. In this paper, we describe the development of MBDS, the way in which it operates today, and some of its achievements. We present key challenges the network has faced and lessons its members have learned about how to develop sufficient trust for health and other professionals to alert each other to disease threats across national borders and thereby more effectively combat these threats.",2013 Jan 25,"['Phommasack, Bounlay', 'Jiraphongsa, Chuleeporn', 'Ko Oo, Moe', 'Bond, Katherine C.', 'Phaholyothin, Natalie', 'Suphanchaimat, Rapeepong', 'Ungchusak, Kumnuan', 'Macfarlane, Sarah B.']",Emerg Health Threats J,,,True
0ca675e1d62eeff5188b3cfa32f4cf16ea634dc4,PMC,Enhanced Surveillance for Detection and Management of Infectious Diseases: Regional Collaboration in the Middle East,http://dx.doi.org/10.3402/ehtj.v6i0.19955,PMC3557910,23362413,CC BY,"Formed before international negotiations of the revised International Health Regulations (IHR), the Middle East Consortium for Infectious Disease Surveillance (MECIDS) is a regional collaboration aimed at facilitating implementation of the revised IHR and, more broadly, improving the detection and control of infectious disease outbreaks among neighboring countries in an area of continuous dispute. Initially focused on enhancing foodborne disease surveillance, MECIDS has expanded the scope of its work to also include avian and pandemic influenza and other emerging and re-emerging infectious diseases. Here, we describe the history and governance of MECIDS, highlighting key achievements over the consortium's seven-year history, and discuss the future of MECIDS.",2013 Jan 25,"['Leventhal, Alex', 'Ramlawi, Assad', 'Belbiesi, Adel', 'Sheikh, Sami', 'Haddadin, Akhtam', 'Husseini, Sari', 'Abdeen, Ziad', 'Cohen, Dani']",Emerg Health Threats J,,,True
04abbb8d91bd1a15a6c70ce3c0bd339f92468265,PMC,Key Findings and Lessons from an Evaluation of the Rockefeller Foundation's Disease Surveillance Networks Initiative,http://dx.doi.org/10.3402/ehtj.v6i0.19959,PMC3557955,23362418,CC BY,,2013 Jan 25,"['MacPherson, Nancy', 'Kimball, Ann Marie', 'Burke, Charlanne', 'Abernethy, Neil', 'Tempongko, Sandra', 'Zinsstag, Jakob']",Emerg Health Threats J,,,True
437c2f5c3e920111eb679f26bde02cbb8a49ff49,PMC,Development of an improved polykaryon-based influenza virus rescue system,http://dx.doi.org/10.1186/1472-6750-12-69,PMC3558383,23009349,CC BY,"BACKGROUND: Virus rescue from transfected cells is an extremely useful technique that allows defined viral clones to be engineered for the purpose of rational vaccine design or fundamental reverse genetics studies. However, it is often hindered by low primary rescue success rates or yields, especially with field-derived viral strains. APPROACH: We investigated the possibility of enhancing influenza virus rescue by eliciting cell fusion to increase the chances of having all necessary plasmids expressed within the same polykaryon. To this end we used the Maedi-Visna Virus envelope protein which has potent fusion activity in cells from a wide range of different species. RESULTS: Co-transfecting cells with the eight plasmids necessary to rescue influenza virus plus a plasmid expressing the Maedi-Visna Virus envelope protein resulted in increased rescue efficiency. In addition, partial complements of the 8-plasmid rescue system could be transfected into two separate populations of cells, which upon fusion led to live virus rescue. CONCLUSION: The simple modification described here has the potential to improve the efficiency of the virus rescue process and expand the potential applications for reverse genetic studies.",2012 Sep 25,"['Bourret, Vincent', 'Lyall, Jon', 'Ducatez, Mariette F', 'Guérin, Jean-Luc', 'Tiley, Laurence']",BMC Biotechnol,,,True
7f5ef8185f8934ab5b5eb4344dad20da84d104a3,PMC,Detection of Bocavirus in Children Suffering from Acute Respiratory Tract Infections in Saudi Arabia,http://dx.doi.org/10.1371/journal.pone.0055500,PMC3559585,23383205,CC BY,"Human bocavirus (HBoV) was recently discovered in children with respiratory distress and/or diarrhea. To our knowledge, no previous study has reported the existence of bocavirus in Saudi Arabia. Swabs samples from 80 children with respiratory tract infections were examined for the presence of HBoV. Real-time polymerase chain reaction was used as a sensitive method to detect the HBoV. Direct gene sequencing was used to determine the genotype of the detected virus isolates. HBoV was detected in 22.5% of the examined patients. The NP1 partial gene sequence from all patients showed that the circulated strains were related to HBoV-1 genotype. Most of HBoV infected patients showed evidence of mixed coinfection with other viral pathogens. The current study clearly demonstrated that genetically conserved HBoV1 circulates in Saudi Arabia. Interestingly, most of the HBoV1 infected cases were associated with high rates of co-infections with other viruses.",2013 Jan 30,"['Abdel-Moneim, Ahmed S.', 'Kamel, Mahmoud M.', 'Al-Ghamdi, Abdullhamid S.', 'Al-Malky, Mater I. R.']",PLoS One,,,True
16a04dc7659daf72dfd1706f843b74d691048b6f,PMC,Porcine epidemic diarrhea virus E protein causes endoplasmic reticulum stress and up-regulates interleukin-8 expression,http://dx.doi.org/10.1186/1743-422X-10-26,PMC3560205,23332027,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is an important pathogen in swine and is responsible for substantial economic losses. Previous studies suggest that the PEDV E protein plays an important role in the viral assembly process. However, the subcellular localization and other functions of PEDV E protein still require more research. METHODS: The subcellular localization and function of PEDV E protein were investigated by examining its effects on cell growth, cell cycle progression, interleukin-8 (IL-8) expression and cell survival. RESULTS: The results show that plenty of PEDV E protein is localized in the ER, with small quantities localized in the nucleus. The PEDV E protein has no effect on the intestinal epithelial cells (IEC) growth, cell cycle and cyclin A expression. The cells expressing PEDV E protein express higher levels of IL-8 than control cells. Further studies show that PEDV E protein induced endoplasmic reticulum (ER) stress and activated NF-κB which is responsible for the up-regulation of IL-8 and Bcl-2 expression. CONCLUSIONS: This study shows that the PEDV E protein is localized in the ER and the nucleus and it can cause ER stress. The PEDV E protein had no effect on the IEC growth and cell cycle. In addition, the PEDV E protein is able to up-regulate IL-8 and Bcl-2 expression.",2013 Jan 19,"['Xu, Xingang', 'Zhang, Honglei', 'Zhang, Qi', 'Dong, Jie', 'Liang, Yabing', 'Huang, Yong', 'Liu, Hung-Jen', 'Tong, Dewen']",Virol J,,,True
0c58c5ce46bfa52188d231685cc1c6a440840b85,PMC,Epidemiology and clinical presentation of the four human parainfluenza virus types,http://dx.doi.org/10.1186/1471-2334-13-28,PMC3560251,23343342,CC BY,"BACKGROUND: Human parainfluenza viruses (HPIVs) are important causes of upper respiratory tract illness (URTI) and lower respiratory tract illness (LRTI). To analyse epidemiologic and clinical characteristics of the four types of human parainfluenza viruses (HPIVs), patients with acute respiratory tract illness (ARTI) were studied in Guangzhou, southern China. METHODS: Throat swabs (n=4755) were collected and tested from children and adults with ARTI over a 26-month period, and 4447 of 4755 (93.5%) patients’ clinical presentations were recorded for further analysis. RESULTS: Of 4755 patients tested, 178 (3.7%) were positive for HPIV. Ninety-nine (2.1%) samples were positive for HPIV-3, 58 (1.2%) for HPIV-1, 19 (0.4%) for HPIV-2 and 8 (0.2%) for HPIV-4. 160/178 (88.9%) HPIV-positive samples were from paediatric patients younger than 5 years old, but no infant under one month of age was HPIV positive. Seasonal peaks of HPIV-3 and HPIV-1 occurred as autumn turned to winter and summer turned to autumn. HPIV-2 and HPIV-4 were detected less frequently, and their frequency of isolation increased when the frequency of HPIV-3 and HPIV-1 declined. HPIV infection led to a wide spectrum of symptoms, and more “hoarseness” (p=0.015), “abnormal pulmonary breathing sound” (p<0.001), “dyspnoea” (p<0.001), “pneumonia” (p=0.01), and “diarrhoea” (p<0.001) presented in HPIV-positive patients than HPIV-negative patients. 10/10 (100%) HPIV-positive adult patients (≥14 years old) presented with systemic influenza-like symptoms, while 90/164 (54.9%) HPIV-positive paediatric patients (<14 years old) presented with these symptoms (p=0.005). The only significant difference in clinical presentation between HPIV types was “Expectoration” (p<0.001). Co-infections were common, with 33.3%–63.2% of samples positive for the four HPIV types also testing positive for other respiratory pathogens. However, no significant differences were seen in clinical presentation between patients solely infected with HPIV and patients co-infected with HPIV and other respiratory pathogens. CONCLUSIONS: HPIV infection led to a wide spectrum of symptoms, and similar clinical manifestations were found in the patients with four different types of HPIVs. The study suggested pathogenic activity of HPIV in gastrointestinal illness. The clinical presentation of HPIV infection may differ by patient age.",2013 Jan 23,"['Liu, Wen-Kuan', 'Liu, Qian', 'Chen, De-Hui', 'Liang, Huan-Xi', 'Chen, Xiao-Kai', 'Huang, Wen-Bo', 'Qin, Sheng', 'Yang, Zi-Feng', 'Zhou, Rong']",BMC Infect Dis,,,True
34e4b49c46c5462089f516983eeb19a6aff69d01,PMC,Inflammatory monocytes and the pathogenesis of viral encephalitis,http://dx.doi.org/10.1186/1742-2094-9-270,PMC3560265,23244217,CC BY,"Monocytes are a heterogeneous population of bone marrow-derived cells that are recruited to sites of infection and inflammation in many models of human diseases, including those of the central nervous system (CNS). Ly6C(hi)/CCR2(hi) inflammatory monocytes have been identified as the circulating precursors of brain macrophages, dendritic cells and arguably microglia in experimental autoimmune encephalomyelitis; Alzheimer’s disease; stroke; and more recently in CNS infection caused by Herpes simplex virus, murine hepatitis virus, Theiler’s murine encephalomyelitis virus, Japanese encephalitis virus and West Nile virus. The precise differentiation pathways and functions of inflammatory monocyte-derived populations in the inflamed CNS remains a contentious issue, especially in regard to the existence of monocyte-derived microglia. Furthermore, the contributions of monocyte-derived subsets to viral clearance and immunopathology are not well-defined. Thus, understanding the pathways through which inflammatory monocytes migrate to the brain and their functional capacity within the CNS is critical to inform future therapeutic strategies. This review discusses some of the key aspects of inflammatory monocyte trafficking to the brain and addresses the role of these cells in viral encephalitis.",2012 Dec 17,"['Terry, Rachael L', 'Getts, Daniel R', 'Deffrasnes, Celine', 'van Vreden, Caryn', 'Campbell, Iain L', 'King, Nicholas JC']",J Neuroinflammation,,,True
50c7a780f9115d0224ceeb6f2e29037d8e5703d8,PMC,Unraveling the Structure of Viral Replication Complexes at Super-Resolution,http://dx.doi.org/10.3389/fpls.2013.00006,PMC3560349,23386855,CC BY,"During infection, many RNA viruses produce characteristic inclusion bodies that contain both viral and host components. These structures were first described over a century ago and originally termed “X-bodies,” as their function was not immediately appreciated. Whilst some inclusion bodies may represent cytopathic by-products of viral protein over-accumulation, X-bodies have emerged as virus “factories,” quasi-organelles that coordinate diverse viral infection processes such as replication, protein expression, evasion of host defenses, virion assembly, and intercellular transport. Accordingly, they are now generally referred to as viral replication complexes (VRCs). We previously used confocal fluorescence microscopy to unravel the complex structure of X-bodies produced by Potato virus X (PVX). Here we used 3D-structured illumination (3D-SIM) super-resolution microscopy to map the PVX X-body at a finer scale. We identify a previously unrecognized membrane structure induced by the PVX “triple gene block” (TGB) proteins, providing new insights into the complex interplay between virus and host within the X-body.",2013 Jan 31,"['Linnik, Olga', 'Liesche, Johannes', 'Tilsner, Jens', 'Oparka, Karl J.']",Front Plant Sci,,,True
19dcbc62263225d430f506aa5745d23a66543de8,PMC,Binding of HIV-1 gp120 to DC-SIGN Promotes ASK-1-Dependent Activation-Induced Apoptosis of Human Dendritic Cells,http://dx.doi.org/10.1371/journal.ppat.1003100,PMC3561151,23382671,CC BY,"During disease progression to AIDS, HIV-1 infected individuals become increasingly immunosuppressed and susceptible to opportunistic infections. It has also been demonstrated that multiple subsets of dendritic cells (DC), including DC-SIGN(+) cells, become significantly depleted in the blood and lymphoid tissues of AIDS patients, which may contribute to the failure in initiating effective host immune responses. The mechanism for DC depletion, however, is unclear. It is also known that vast quantities of viral envelope protein gp120 are shed from maturing HIV-1 virions and form circulating immune complexes in the serum of HIV-1-infected individuals, but the pathological role of gp120 in HIV-1 pathogenesis remains elusive. Here we describe a previously unrecognized mechanism of DC death in chronic HIV-1 infection, in which ligation of DC-SIGN by gp120 sensitizes DC to undergo accelerated apoptosis in response to a variety of activation stimuli. The cultured monocyte-derived DC and also freshly-isolated DC-SIGN(+) blood DC that were exposed to either cross-linked recombinant gp120 or immune-complex gp120 in HIV(+) serum underwent considerable apoptosis after CD40 ligation or exposure to bacterial lipopolysaccharide (LPS) or pro-inflammatory cytokines such as TNFα and IL-1β. Furthermore, circulating DC-SIGN(+) DC that were isolated directly from HIV-1(+) individuals had actually been pre-sensitized by serum gp120 for activation-induced exorbitant apoptosis. In all cases the DC apoptosis was substantially inhibited by DC-SIGN blockade. Finally, we showed that accelerated DC apoptosis was a direct consequence of excessive activation of the pro-apoptotic molecule ASK-1 and transfection of siRNA against ASK-1 significantly prevented the activation-induced excessive DC death. Our study discloses a previously unknown mechanism of immune modulation by envelope protein gp120, provides new insights into HIV immunopathogenesis, and suggests potential therapeutic approaches to prevent DC depletion in chronic HIV infection.",2013 Jan 31,"['Chen, Yongxiong', 'Hwang, Shiuh-Lin', 'Chan, Vera S. F.', 'Chung, Nancy P. Y.', 'Wang, Shu-Rong', 'Li, Zhongye', 'Ma, Jing', 'Lin, Chia-Wei', 'Hsieh, Ya-Ju', 'Chang, Kao-Ping', 'Kung, Sui-Sum', 'Wu, Yi-Chia', 'Chu, Cheng-Wei', 'Tai, Hsiao-Ting', 'Gao, George F.', 'Zheng, Bojian', 'Yokoyama, Kazunari K.', 'Austyn, Jonathan M.', 'Lin, Chen-Lung S.']",PLoS Pathog,,,True
5efae4eb4c986da7483e7628d420be2a29df90d0,PMC,Differential Response of Primary Alveolar Type I and Type II Cells to LPS Stimulation,http://dx.doi.org/10.1371/journal.pone.0055545,PMC3561226,23383221,CC0,"The alveolar epithelium serves as a barrier between organism and environment and functions as the first line of protection against potential respiratory pathogens. Alveolar type II (TII) cells have traditionally been considered the immune cells of the alveolar epithelium, as they possess immunomodulatory functions; however, the precise role of alveolar type I (TI) cells, which comprise ∼95% of the alveolar epithelial surface area, in lung immunity is not clear. We sought to determine if there was a difference in the response of TI and TII cells to lung injury and if TI cells could actively participate in the alveolar immune response. TI cells isolated via fluorescence activated cell sorting (FACS) from LPS-injured rats demonstrated greater fold-induction of multiple inflammatory mediators than TII cells isolated in the same manner from the same animals. Levels of the cytokines TNF-α, IL-6 and IL-1β from cultured primary rat TI cells after LPS stimulation were significantly increased compared to similarly studied primary rat TII cells. We found that contrary to published reports, cultured TII cells produce relatively small amounts of TNF-α, IL-6 and IL-1β after LPS treatment; the higher levels of cytokine expression from cultured TII cells reported in the literature were likely from macrophage contamination due to traditional non-FACS TII cell isolation methods. Co-culture of TII cells with macrophages prior to LPS stimulation increased TNF-α and IL-6 production to levels reported by other investigators for TII cells, however, co-culture of TI cells and macrophages prior to LPS treatment resulted in marked increases in TNF-α and IL-6 production. Finally, exogenous surfactant blunted the IL-6 response to LPS in cultured TI cells. Taken together, these findings advocate a role for TI cells in the innate immune response and suggest that both TI and TII cells are active players in host defense mechanisms in the lung.",2013 Jan 31,"['Wong, Mandi H.', 'Johnson, Meshell D.']",PLoS One,,,True
83f15da5d4de38afb2d1ba4b482f66d4e623c11e,PMC,An Upstream Open Reading Frame Modulates Ebola Virus Polymerase Translation and Virus Replication,http://dx.doi.org/10.1371/journal.ppat.1003147,PMC3561295,23382680,CC0,"Ebolaviruses, highly lethal zoonotic pathogens, possess longer genomes than most other non-segmented negative-strand RNA viruses due in part to long 5′ and 3′ untranslated regions (UTRs) present in the seven viral transcriptional units. To date, specific functions have not been assigned to these UTRs. With reporter assays, we demonstrated that the Zaire ebolavirus (EBOV) 5′-UTRs lack internal ribosomal entry site function. However, the 5′-UTRs do differentially regulate cap-dependent translation when placed upstream of a GFP reporter gene. Most dramatically, the 5′-UTR derived from the viral polymerase (L) mRNA strongly suppressed translation of GFP compared to a β-actin 5′-UTR. The L 5′-UTR is one of four viral genes to possess upstream AUGs (uAUGs), and ablation of each uAUG enhanced translation of the primary ORF (pORF), most dramatically in the case of the L 5′-UTR. The L uAUG was sufficient to initiate translation, is surrounded by a “weak” Kozak sequence and suppressed pORF translation in a position-dependent manner. Under conditions where eIF2α was phosphorylated, the presence of the uORF maintained translation of the L pORF, indicating that the uORF modulates L translation in response to cellular stress. To directly address the role of the L uAUG in virus replication, a recombinant EBOV was generated in which the L uAUG was mutated to UCG. Strikingly, mutating two nucleotides outside of previously-defined protein coding and cis-acting regulatory sequences attenuated virus growth to titers 10–100-fold lower than a wild-type virus in Vero and A549 cells. The mutant virus also exhibited decreased viral RNA synthesis as early as 6 hours post-infection and enhanced sensitivity to the stress inducer thapsigargin. Cumulatively, these data identify novel mechanisms by which EBOV regulates its polymerase expression, demonstrate their relevance to virus replication and identify a potential therapeutic target.",2013 Jan 31,"['Shabman, Reed S.', 'Hoenen, Thomas', 'Groseth, Allison', 'Jabado, Omar', 'Binning, Jennifer M.', 'Amarasinghe, Gaya K.', 'Feldmann, Heinz', 'Basler, Christopher F.']",PLoS Pathog,,,True
a65ed49e9217467923e8db733109be6e54b0bd09,PMC,Quantitative analysis of ciliary beating in primary ciliary dyskinesia: a pilot study,http://dx.doi.org/10.1186/1750-1172-7-78,PMC3562218,23057704,CC BY,"BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare congenital respiratory disorder characterized by abnormal ciliary motility leading to chronic airway infections. Qualitative evaluation of ciliary beat pattern based on digital high-speed videomicroscopy analysis has been proposed in the diagnosis process of PCD. Although this evaluation is easy in typical cases, it becomes difficult when ciliary beating is partially maintained. We postulated that a quantitative analysis of beat pattern would improve PCD diagnosis. We compared quantitative parameters with the qualitative evaluation of ciliary beat pattern in patients in whom the diagnosis of PCD was confirmed or excluded. METHODS: Nasal nitric oxide measurement, nasal brushings and biopsies were performed prospectively in 34 patients with suspected PCD. In combination with qualitative analysis, 12 quantitative parameters of ciliary beat pattern were determined on high-speed videomicroscopy recordings of beating ciliated edges. The combination of ciliary ultrastructural abnormalities on transmission electron microscopy analysis with low nasal nitric oxide levels was the “gold standard” used to establish the diagnosis of PCD. RESULTS: This “gold standard” excluded PCD in 15 patients (non-PCD patients), confirmed PCD in 10 patients (PCD patients) and was inconclusive in 9 patients. Among the 12 parameters, the distance traveled by the cilium tip weighted by the percentage of beating ciliated edges presented 96% sensitivity and 95% specificity. Qualitative evaluation and quantitative analysis were concordant in non-PCD patients. In 9/10 PCD patients, quantitative analysis was concordant with the “gold standard”, while the qualitative evaluation was discordant with the “gold standard” in 3/10 cases. Among the patients with an inconclusive “gold standard”, the use of quantitative parameters supported PCD diagnosis in 4/9 patients (confirmed by the identification of disease-causing mutations in one patient) and PCD exclusion in 2/9 patients. CONCLUSIONS: When the beat pattern is normal or virtually immotile, the qualitative evaluation is adequate to study ciliary beating in patients suspected for PCD. However, when cilia are still beating but with moderate alterations (more than 40% of patients suspected for PCD), quantitative analysis is required to precise the diagnosis and can be proposed to select patients eligible for TEM.",2012 Oct 11,"['Papon, Jean-François', 'Bassinet, Laurence', 'Cariou-Patron, Gwenaëlle', 'Zerah-Lancner, Francoise', 'Vojtek, Anne-Marie', 'Blanchon, Sylvain', 'Crestani, Bruno', 'Amselem, Serge', 'Coste, Andre', 'Housset, Bruno', 'Escudier, Estelle', 'Louis, Bruno']",Orphanet J Rare Dis,,,True
d148bed5cf622c1a263907a3cbf8c6d533edded8,PMC,Inhibitors of the Influenza A Virus M2 Proton Channel Discovered Using a High-Throughput Yeast Growth Restoration Assay,http://dx.doi.org/10.1371/journal.pone.0055271,PMC3562233,23383318,CC BY,"The M2 proton channel of the influenza A virus is the target of the anti-influenza drugs amantadine and rimantadine. The effectiveness of these drugs has been dramatically limited by the rapid spread of drug resistant mutations, mainly at sites S31N, V27A and L26F in the pore of the channel. Despite progress in designing inhibitors of V27A and L26F M2, there are currently no drugs targeting these mutated channels in clinical trials. Progress in developing new drugs has been hampered by the lack of a robust assay with sufficient throughput for discovery of new active chemotypes among chemical libraries and sufficient sensitivity to provide the SAR data essential for their improvement and development as drugs. In this study we adapted a yeast growth restoration assay, in which expression of the M2 channel inhibits yeast growth and exposure to an M2 channel inhibitor restores growth, into a robust and sensitive high-throughput screen for M2 channel inhibitors. A screen of over 250,000 pure chemicals and semi-purified fractions from natural extracts identified 21 active compounds comprising amantadine, rimantadine, 13 related adamantanes and 6 non-adamantanes. Of the non-adamantanes, hexamethylene amiloride and a triazine derivative represented new M2 inhibitory chemotypes that also showed antiviral activity in a plaque reduction assay. Of particular interest is the fact that the triazine derivative was not sufficiently potent for detection as an inhibitor in the traditional two electrode voltage clamp assay for M2 channel activity, but its discovery in the yeast assay led to testing of analogues of which one was as potent as amantadine.",2013 Feb 1,"['Balgi, Aruna D.', 'Wang, Jun', 'Cheng, Daphne Y. H.', 'Ma, Chunlong', 'Pfeifer, Tom A.', 'Shimizu, Yoko', 'Anderson, Hilary J.', 'Pinto, Lawrence H.', 'Lamb, Robert A.', 'DeGrado, William F.', 'Roberge, Michel']",PLoS One,,,True
1cc437f58a3eda9fc4e73c1cabb18964d2a7e705,PMC,Inhibitors of the Influenza A Virus M2 Proton Channel Discovered Using a High-Throughput Yeast Growth Restoration Assay,http://dx.doi.org/10.1371/journal.pone.0055271,PMC3562233,23383318,CC BY,"The M2 proton channel of the influenza A virus is the target of the anti-influenza drugs amantadine and rimantadine. The effectiveness of these drugs has been dramatically limited by the rapid spread of drug resistant mutations, mainly at sites S31N, V27A and L26F in the pore of the channel. Despite progress in designing inhibitors of V27A and L26F M2, there are currently no drugs targeting these mutated channels in clinical trials. Progress in developing new drugs has been hampered by the lack of a robust assay with sufficient throughput for discovery of new active chemotypes among chemical libraries and sufficient sensitivity to provide the SAR data essential for their improvement and development as drugs. In this study we adapted a yeast growth restoration assay, in which expression of the M2 channel inhibits yeast growth and exposure to an M2 channel inhibitor restores growth, into a robust and sensitive high-throughput screen for M2 channel inhibitors. A screen of over 250,000 pure chemicals and semi-purified fractions from natural extracts identified 21 active compounds comprising amantadine, rimantadine, 13 related adamantanes and 6 non-adamantanes. Of the non-adamantanes, hexamethylene amiloride and a triazine derivative represented new M2 inhibitory chemotypes that also showed antiviral activity in a plaque reduction assay. Of particular interest is the fact that the triazine derivative was not sufficiently potent for detection as an inhibitor in the traditional two electrode voltage clamp assay for M2 channel activity, but its discovery in the yeast assay led to testing of analogues of which one was as potent as amantadine.",2013 Feb 1,"['Balgi, Aruna D.', 'Wang, Jun', 'Cheng, Daphne Y. H.', 'Ma, Chunlong', 'Pfeifer, Tom A.', 'Shimizu, Yoko', 'Anderson, Hilary J.', 'Pinto, Lawrence H.', 'Lamb, Robert A.', 'DeGrado, William F.', 'Roberge, Michel']",PLoS One,,,False
97d3189bef9a6aa37975b4fe0da23c7c0ea1dae9,PMC,Inhibitors of the Influenza A Virus M2 Proton Channel Discovered Using a High-Throughput Yeast Growth Restoration Assay,http://dx.doi.org/10.1371/journal.pone.0055271,PMC3562233,23383318,CC BY,"The M2 proton channel of the influenza A virus is the target of the anti-influenza drugs amantadine and rimantadine. The effectiveness of these drugs has been dramatically limited by the rapid spread of drug resistant mutations, mainly at sites S31N, V27A and L26F in the pore of the channel. Despite progress in designing inhibitors of V27A and L26F M2, there are currently no drugs targeting these mutated channels in clinical trials. Progress in developing new drugs has been hampered by the lack of a robust assay with sufficient throughput for discovery of new active chemotypes among chemical libraries and sufficient sensitivity to provide the SAR data essential for their improvement and development as drugs. In this study we adapted a yeast growth restoration assay, in which expression of the M2 channel inhibits yeast growth and exposure to an M2 channel inhibitor restores growth, into a robust and sensitive high-throughput screen for M2 channel inhibitors. A screen of over 250,000 pure chemicals and semi-purified fractions from natural extracts identified 21 active compounds comprising amantadine, rimantadine, 13 related adamantanes and 6 non-adamantanes. Of the non-adamantanes, hexamethylene amiloride and a triazine derivative represented new M2 inhibitory chemotypes that also showed antiviral activity in a plaque reduction assay. Of particular interest is the fact that the triazine derivative was not sufficiently potent for detection as an inhibitor in the traditional two electrode voltage clamp assay for M2 channel activity, but its discovery in the yeast assay led to testing of analogues of which one was as potent as amantadine.",2013 Feb 1,"['Balgi, Aruna D.', 'Wang, Jun', 'Cheng, Daphne Y. H.', 'Ma, Chunlong', 'Pfeifer, Tom A.', 'Shimizu, Yoko', 'Anderson, Hilary J.', 'Pinto, Lawrence H.', 'Lamb, Robert A.', 'DeGrado, William F.', 'Roberge, Michel']",PLoS One,,,False
f4f36a8e9fee64d59ccf22b724c7dab345102658,PMC,One step closer to an experimental infection system for Hepatitis B Virus? --- the identification of sodium taurocholate cotransporting peptide as a viral receptor,http://dx.doi.org/10.1186/2045-3701-3-2,PMC3562259,23311606,CC BY,"Following the successful cloning of receptor for SARS coronavirus a few years ago, Dr. Wenhui Li and colleagues raised attention again by publishing a possible receptor for hepatitis B virus in eLife. We will briefly review the significance of this finding and the future prospects of hepatitis B research.",2013 Jan 11,"['Chen, Pei-Jer', 'Wu, T-C']",Cell Biosci,,,True
4b92357afea168410a305eca0e593b7955f08598,PMC,Controlling epidemic spread by social distancing: Do it well or not at all,http://dx.doi.org/10.1186/1471-2458-12-679,PMC3563464,22905965,CC BY,"BACKGROUND: Existing epidemiological models have largely tended to neglect the impact of individual behaviour on the dynamics of diseases. However, awareness of the presence of illness can cause people to change their behaviour by, for example, staying at home and avoiding social contacts. Such changes can be used to control epidemics but they exact an economic cost. Our aim is to study the costs and benefits of using individual-based social distancing undertaken by healthy individuals as a form of control. METHODS: Our model is a standard SIR model superimposed on a spatial network, without and with addition of small-world interactions. Disease spread is controlled by allowing susceptible individuals to temporarily reduce their social contacts in response to the presence of infection within their local neighbourhood. We ascribe an economic cost to the loss of social contacts, and weigh this against the economic benefit gained by reducing the impact of the epidemic. We study the sensitivity of the results to two key parameters, the individuals’ attitude to risk and the size of the awareness neighbourhood. RESULTS: Depending on the characteristics of the epidemic and on the relative economic importance of making contacts versus avoiding infection, the optimal control is one of two extremes: either to adopt a highly cautious control, thereby suppressing the epidemic quickly by drastically reducing contacts as soon as disease is detected; or else to forego control and allow the epidemic to run its course. The worst outcome arises when control is attempted, but not cautiously enough to cause the epidemic to be suppressed. The next main result comes from comparing the size of the neighbourhood of which individuals are aware to that of the neighbourhood within which transmission can occur. The control works best when these sizes match and is particularly ineffective when the awareness neighbourhood is smaller than the infection neighbourhood. The results are robust with respect to inclusion of long-range, small-world links which destroy the spatial structure, regardless of whether individuals can or cannot control them. However, addition of many non-local links eventually makes control ineffective. CONCLUSIONS: These results have implications for the design of control strategies using social distancing: a control that is too weak or based upon inaccurate knowledge, may give a worse outcome than doing nothing.",2012 Aug 20,"['Maharaj, Savi', 'Kleczkowski, Adam']",BMC Public Health,,,True
05b8deee7f76cda7511eb605e2ba84a8f46bc10f,PMC,Insights into the Roles of Cyclophilin A During Influenza Virus Infection,http://dx.doi.org/10.3390/v5010182,PMC3564116,23322171,CC BY,"Cyclophilin A (CypA) is the main member of the immunophilin superfamily that has peptidyl-prolyl cis-trans isomerase activity. CypA participates in protein folding, cell signaling, inflammation and tumorigenesis. Further, CypA plays critical roles in the replication of several viruses. Upon influenza virus infection, CypA inhibits viral replication by interacting with the M1 protein. In addition, CypA is incorporated into the influenza virus virions. Finally, Cyclosporin A (CsA), the main inhibitor of CypA, inhibits influenza virus replication through CypA-dependent and -independent pathways. This review briefly summarizes recent advances in understanding the roles of CypA during influenza virus infection.",2013 Jan 15,"['Liu, Xiaoling', 'Zhao, Zhendong', 'Liu, Wenjun']",Viruses,,,True
a31ae2d95b283ef7da701d343b992b25afa779d8,PMC,Altering SARS Coronavirus Frameshift Efficiency Affects Genomic and Subgenomic RNA Production,http://dx.doi.org/10.3390/v5010279,PMC3564121,23334702,CC BY,"In previous studies, differences in the amount of genomic and subgenomic RNA produced by coronaviruses with mutations in the programmed ribosomal frameshift signal of ORF1a/b were observed. It was not clear if these differences were due to changes in genomic sequence, the protein sequence or the frequency of frameshifting. Here, viruses with synonymous codon changes are shown to produce different ratios of genomic and subgenomic RNA. These findings demonstrate that the protein sequence is not the primary cause of altered genomic and subgenomic RNA production. The synonymous codon changes affect both the structure of the frameshift signal and frameshifting efficiency. Small differences in frameshifting efficiency result in dramatic differences in genomic RNA production and TCID(50) suggesting that the frameshifting frequency must stay above a certain threshold for optimal virus production. The data suggest that either the RNA sequence or the ratio of viral proteins resulting from different levels of frameshifting affects viral replication.",2013 Jan 18,"['Plant, Ewan P.', 'Sims, Amy C.', 'Baric, Ralph S.', 'Dinman, Jonathan D.', 'Taylor, Deborah R.']",Viruses,,,True
04fa24d6f02d6b2fd44a0cb7aa2a7e7149e6cacc,PMC,Influenza A Virus Entry Inhibitors Targeting the Hemagglutinin,http://dx.doi.org/10.3390/v5010352,PMC3564125,23340380,CC BY,"Influenza A virus (IAV) has caused seasonal influenza epidemics and influenza pandemics, which resulted in serious threat to public health and socioeconomic impacts. Until now, only 5 drugs belong to two categories are used for prophylaxis and treatment of IAV infection. Hemagglutinin (HA), the envelope glycoprotein of IAV, plays a critical role in viral binding, fusion and entry. Therefore, HA is an attractive target for developing anti‑IAV drugs to block the entry step of IAV infection. Here we reviewed the recent progress in the study of conformational changes of HA during viral fusion process and the development of HA-based IAV entry inhibitors, which may provide a new choice for controlling future influenza pandemics.",2013 Jan 22,"['Yang, Jie', 'Li, Minmin', 'Shen, Xintian', 'Liu, Shuwen']",Viruses,,,True
5739f33d00bed835fb29dd26757a04faf48905a5,PMC,Reconstitution of Membrane Proteins into Model Membranes: Seeking Better Ways to Retain Protein Activities,http://dx.doi.org/10.3390/ijms14011589,PMC3565336,23344058,CC BY,"The function of any given biological membrane is determined largely by the specific set of integral membrane proteins embedded in it, and the peripheral membrane proteins attached to the membrane surface. The activity of these proteins, in turn, can be modulated by the phospholipid composition of the membrane. The reconstitution of membrane proteins into a model membrane allows investigation of individual features and activities of a given cell membrane component. However, the activity of membrane proteins is often difficult to sustain following reconstitution, since the composition of the model phospholipid bilayer differs from that of the native cell membrane. This review will discuss the reconstitution of membrane protein activities in four different types of model membrane—monolayers, supported lipid bilayers, liposomes and nanodiscs, comparing their advantages in membrane protein reconstitution. Variation in the surrounding model environments for these four different types of membrane layer can affect the three-dimensional structure of reconstituted proteins and may possibly lead to loss of the proteins activity. We also discuss examples where the same membrane proteins have been successfully reconstituted into two or more model membrane systems with comparison of the observed activity in each system. Understanding of the behavioral changes for proteins in model membrane systems after membrane reconstitution is often a prerequisite to protein research. It is essential to find better solutions for retaining membrane protein activities for measurement and characterization in vitro.",2013 Jan 14,"['Shen, Hsin-Hui', 'Lithgow, Trevor', 'Martin, Lisandra L.']",Int J Mol Sci,,,True
e005630bf0183fb7a78efa065c0c545922d27009,PMC,Generating super-shedders: co-infection increases bacterial load and egg production of a gastrointestinal helminth,http://dx.doi.org/10.1098/rsif.2012.0588,PMC3565725,23256186,CC BY,"Co-infection by multiple parasites is common within individuals. Interactions between co-infecting parasites include resource competition, direct competition and immune-mediated interactions and each are likely to alter the dynamics of single parasites. We posit that co-infection is a driver of variation in parasite establishment and growth, ultimately altering the production of parasite transmission stages. To test this hypothesis, three different treatment groups of laboratory mice were infected with the gastrointestinal helminth Heligmosomoides polygyrus, the respiratory bacterial pathogen Bordetella bronchiseptica lux(+) or co-infected with both parasites. To follow co-infection simultaneously, self-bioluminescent bacteria were used to quantify infection in vivo and in real-time, while helminth egg production was monitored in real-time using faecal samples. Co-infection resulted in high bacterial loads early in the infection (within the first 5 days) that could cause host mortality. Co-infection also produced helminth ‘super-shedders’; individuals that chronically shed the helminth eggs in larger than average numbers. Our study shows that co-infection may be one of the underlying mechanisms for the often-observed high variance in parasite load and shedding rates, and should thus be taken into consideration for disease management and control. Further, using self-bioluminescent bacterial reporters allowed quantification of the progression of infection within the whole animal of the same individuals at a fine temporal scale (daily) and significantly reduced the number of animals used (by 85%) compared with experiments that do not use in vivo techniques. Thus, we present bioluminescent imaging as a novel, non-invasive tool offering great potential to be taken forward into other applications of infectious disease ecology.",2013 Mar 6,"['Lass, Sandra', 'Hudson, Peter J.', 'Thakar, Juilee', 'Saric, Jasmina', 'Harvill, Eric', 'Albert, Réka', 'Perkins, Sarah E.']",J R Soc Interface,,,True
4fc7caae919d6b80f27561b9d034650a220affbb,PMC,Inferring population-level contact heterogeneity from common epidemic data,http://dx.doi.org/10.1098/rsif.2012.0578,PMC3565785,23034353,CC BY,"Models of infectious disease spread that incorporate contact heterogeneity through contact networks are an important tool for epidemiologists studying disease dynamics and assessing intervention strategies. One of the challenges of contact network epidemiology has been the difficulty of collecting individual and population-level data needed to develop an accurate representation of the underlying host population's contact structure. In this study, we evaluate the utility of common epidemiological measures (R(0), epidemic peak size, duration and final size) for inferring the degree of heterogeneity in a population's unobserved contact structure through a Bayesian approach. We test the method using ground truth data and find that some of these epidemiological metrics are effective at classifying contact heterogeneity. The classification is also consistent across pathogen transmission probabilities, and so can be applied even when this characteristic is unknown. In particular, the reproductive number, R(0), turns out to be a poor classifier of the degree heterogeneity, while, unexpectedly, final epidemic size is a powerful predictor of network structure across the range of heterogeneity. We also evaluate our framework on empirical epidemiological data from past and recent outbreaks to demonstrate its application in practice and to gather insights about the relevance of particular contact structures for both specific systems and general classes of infectious disease. We thus introduce a simple approach that can shed light on the unobserved connectivity of a host population given epidemic data. Our study has the potential to inform future data-collection efforts and study design by driving our understanding of germane epidemic measures, and highlights a general inferential approach to learning about host contact structure in contemporary or historic populations of humans and animals.",2013 Jan 6,"['Stack, J. Conrad', 'Bansal, Shweta', 'Kumar, V. S. Anil', 'Grenfell, Bryan']",J R Soc Interface,,,True
5b965255f0dc3c8ef81a95673bcbfe57d902010f,PMC,Clinical development of monoclonal antibody-based drugs in HIV and HCV diseases,http://dx.doi.org/10.1186/1741-7015-11-4,PMC3565905,23289632,CC BY,"Today there are many licensed antiviral drugs, but the emergence of drug resistant strains sometimes invalidates the effects of the current therapies used in the treatment of infectious diseases. Compared to conventional antiviral drugs, monoclonal antibodies (mAbs) used as pharmacological molecules have particular physical characteristics and modes of action, and, therefore, they should be considered as a distinct therapeutic class. Despite being historically validated, antibodies may represent a novel tool for combatting infectious diseases. The current high cost of mAbs' production, storage and administration (by injection only) and the consequent obstacles to development are outweighed by mAbs' clinical advantages. These are related to a low toxicity combined with high specificity and versatility, which allows a specific antibody to mediate various biological effects, ranging from the virus neutralization mechanisms to the modulation of immune responses. This review briefly summarizes the recent technological advances in the field of immunoglobulin research, and the current status of mAb-based drugs in clinical trials for HIV and HCV diseases. For each clinical trial the available data are reported and the emerging conceptual problems of the employed mAbs are highlighted. This overview helps to give a clear picture of the efficacy and challenges of the mAbs in the field of these two infectious diseases which have such a global impact.",2013 Jan 4,"['Flego, Michela', 'Ascione, Alessandro', 'Cianfriglia, Maurizio', 'Vella, Stefano']",BMC Med,,,True
60e49bb744eb678ae1ac1fb9bb920a5b01954041,PMC,An analysis of the health status of the United Arab Emirates: the ‘Big 4’ public health issues,http://dx.doi.org/10.3402/gha.v6i0.20100,PMC3566378,23394856,CC BY,"BACKGROUND: The United Arab Emirates (UAE) is a rapidly developing country composed of a multinational population with varying educational backgrounds, religious beliefs, and cultural practices, which pose a challenge for population-based public health strategies. A number of public health issues significantly contribute to morbidity and mortality in the UAE. This article summarises the findings of a panel of medical and public health specialists from UAE University and various government health agencies commissioned to report on the health status of the UAE population. METHODS: A systematic literature search was conducted to retrieve peer-reviewed articles on health in the UAE, and unpublished data were provided by government health authorities and local hospitals. RESULTS: The panel reviewed and evaluated all available evidence to list and rank (1=highest priority) the top four main public health issues: 1) Cardiovascular disease accounted for more than 25% of deaths in 2010; 2) Injury caused 17% of mortality for all age groups in 2010; 3) Cancer accounted for 10% of all deaths in 2010, and the incidence of all cancers is projected to double by 2020; and 4) Respiratory disorders were the second most common non-fatal condition in 2010. CONCLUSION: The major public health challenges posed by certain personal (e.g. ethnicity, family history), lifestyle, occupational, and environmental factors associated with the development of chronic disease are not isolated to the UAE; rather, they form part of a global health problem, which requires international collaboration and action. Future research should focus on population-based public health interventions that target the factors associated with the development of various chronic diseases.",2013 Feb 5,"['Loney, Tom', 'Aw, Tar-Ching', 'Handysides, Daniel G.', 'Ali, Raghib', 'Blair, Iain', 'Grivna, Michal', 'Shah, Syed M.', 'Sheek-Hussein, Mohamud', 'El-Sadig, Mohamed', 'Sharif, Amer A.', 'El-Obaid, Yusra']",Glob Health Action,,,True
ee48061797d29eeef5a9e606841bf8ab04b1d75b,PMC,Vesicular stomatitis virus with the rabies virus glycoprotein directs retrograde transsynaptic transport among neurons in vivo,http://dx.doi.org/10.3389/fncir.2013.00011,PMC3566411,23403489,CC BY,"Defining the connections among neurons is critical to our understanding of the structure and function of the nervous system. Recombinant viruses engineered to transmit across synapses provide a powerful approach for the dissection of neuronal circuitry in vivo. We recently demonstrated that recombinant vesicular stomatitis virus (VSV) can be endowed with anterograde or retrograde transsynaptic tracing ability by providing the virus with different glycoproteins. Here we extend the characterization of the transmission and gene expression of recombinant VSV (rVSV) with the rabies virus glycoprotein (RABV-G), and provide examples of its activity relative to the anterograde transsynaptic tracer form of rVSV. rVSV with RABV-G was found to drive strong expression of transgenes and to spread rapidly from neuron to neuron in only a retrograde manner. Depending upon how the RABV-G was delivered, VSV served as a polysynaptic or monosynaptic tracer, or was able to define projections through axonal uptake and retrograde transport. In animals co-infected with rVSV in its anterograde form, rVSV with RABV-G could be used to begin to characterize the similarities and differences in connections to different areas. rVSV with RABV-G provides a flexible, rapid, and versatile tracing tool that complements the previously described VSV-based anterograde transsynaptic tracer.",2013 Feb 7,"['Beier, Kevin T.', 'Saunders, Arpiar B.', 'Oldenburg, Ian A.', 'Sabatini, Bernardo L.', 'Cepko, Constance L.']",Front Neural Circuits,,,True
2df20f5c298fe15e93bc70a752c8566c367f0faa,PMC,Isolation of a Novel Swine Influenza Virus from Oklahoma in 2011 Which Is Distantly Related to Human Influenza C Viruses,http://dx.doi.org/10.1371/journal.ppat.1003176,PMC3567177,23408893,CC BY,"Of the Orthomyxoviridae family of viruses, only influenza A viruses are thought to exist as multiple subtypes and has non-human maintenance hosts. In April 2011, nasal swabs were collected for virus isolation from pigs exhibiting influenza-like illness. Subsequent electron microscopic, biochemical, and genetic studies identified an orthomyxovirus with seven RNA segments exhibiting approximately 50% overall amino acid identity to human influenza C virus. Based on its genetic organizational similarities to influenza C viruses this virus has been provisionally designated C/Oklahoma/1334/2011 (C/OK). Phylogenetic analysis of the predicted viral proteins found that the divergence between C/OK and human influenza C viruses was similar to that observed between influenza A and B viruses. No cross reactivity was observed between C/OK and human influenza C viruses using hemagglutination inhibition (HI) assays. Additionally, screening of pig and human serum samples found that 9.5% and 1.3%, respectively, of individuals had measurable HI antibody titers to C/OK virus. C/OK virus was able to infect both ferrets and pigs and transmit to naive animals by direct contact. Cell culture studies showed that C/OK virus displayed a broader cellular tropism than a human influenza C virus. The observed difference in cellular tropism was further supported by structural analysis showing that hemagglutinin esterase (HE) proteins between two viruses have conserved enzymatic but divergent receptor-binding sites. These results suggest that C/OK virus represents a new subtype of influenza C viruses that currently circulates in pigs that has not been recognized previously. The presence of multiple subtypes of co-circulating influenza C viruses raises the possibility of reassortment and antigenic shift as mechanisms of influenza C virus evolution.",2013 Feb 7,"['Hause, Ben M.', 'Ducatez, Mariette', 'Collin, Emily A.', 'Ran, Zhiguang', 'Liu, Runxia', 'Sheng, Zizhang', 'Armien, Anibal', 'Kaplan, Bryan', 'Chakravarty, Suvobrata', 'Hoppe, Adam D.', 'Webby, Richard J.', 'Simonson, Randy R.', 'Li, Feng']",PLoS Pathog,,,True
bcfa3dbb3fadcb51bd684e07b654328d2bf4e0db,PMC,Continuous intravenous anaesthesia with sufentanil and midazolam in medetomidine premedicated New Zealand White rabbits,http://dx.doi.org/10.1186/1746-6148-9-21,PMC3568725,23351150,CC BY,"BACKGROUND: Anaesthesia in rabbits is associated with a high mortality rate, compared to that in cats and dogs. Total intravenous anaesthesia (TIVA) with drugs that provide cardiovascular stability and are rapidly metabolised could be of benefit for use in rabbits. The aim was to evaluate cardiorespiratory effects of TIVA with sufentanil-midazolam in eight New Zealand White rabbits. Subcutaneous premedication with medetomidine (0.1 mg/kg BW) was followed by IV administration of a mixture of 2.5 μg/mL sufentanil and 0.45 mg/mL midazolam at a rate of 0.3 mL/kg BW/h for anaesthetic induction. Additionally, intravenous boluses of 0.1 mL of the mixture were administered every 20 s until the righting reflex was lost. Following endotracheal intubation, anaesthesia was maintained for 60 min with an infusion rate adjusted to supress the pedal withdrawal reflex. Air and oxygen (1:2) were delivered at 3 L/min. Physiological variables were recorded before induction and at predefined time points during and after anaesthesia. RESULTS: Righting and pedal withdrawal reflexes were lost within 3 and 5 min, respectively. Doses of sufentanil and midazolam were 0.48 μg/kg BW and 0.09 mg/kg BW for induction, and 0.72 μg/kg BW/h and 0.13 mg/kg BW/h for maintenance. Apnoea occurred in two rabbits. Induction of anaesthesia caused a significant increase in heart rate, cardiac output and arterial CO(2) partial pressure and a decrease in mean arterial pressure, respiratory rate and pH. Mean time from stopping the infusion to endotracheal extubation was 5 min, and to return of the righting reflex 7 min. Anaesthesia was characterized by induction and recovery without excitation, with muscle relaxation, and absence of the pedal withdrawal reflex. CONCLUSIONS: TIVA with sufentanil-midazolam provided smooth induction and recovery of anaesthesia in rabbits but with marked hypotension and respiratory depression, requiring mechanical ventilation. Further evaluation is needed to establish if the protocol is useful for rabbits undergoing surgery.",2013 Jan 28,"['Hedenqvist, Patricia', 'Edner, Anna', 'Fahlman, Åsa', 'Jensen-Waern, Marianne']",BMC Vet Res,,,True
1449e7aedd623536a61d71bf1505622093774208,PMC,Isolation and molecular characterization of type I and type II feline coronavirus in Malaysia,http://dx.doi.org/10.1186/1743-422X-9-278,PMC3568730,23171743,CC BY,"BACKGROUND: Feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV) are two important coronaviruses of domestic cat worldwide. Although FCoV is prevalent among cats; the fastidious nature of type I FCoV to grow on cell culture has limited further studies on tissue tropism and pathogenesis of FCoV. While several studies reported serological evidence for FCoV in Malaysia, neither the circulating FCoV isolated nor its biotypes determined. This study for the first time, describes the isolation and biotypes determination of type I and type II FCoV from naturally infected cats in Malaysia. FINDINGS: Of the total number of cats sampled, 95% (40/42) were RT-PCR positive for FCoV. Inoculation of clinical samples into Crandell feline kidney cells (CrFK), and Feline catus whole fetus-4 cells (Fcwf-4), show cytopathic effect (CPE) characterized by syncytial cells formation and later cell detachment. Differentiation of FCoV biotypes using RT-PCR assay revealed that, 97.5% and 2.5% of local isolates were type I and type II FCoV, respectively. These isolates had high sequence homology and phylogenetic similarity with several FCoV isolates from Europe, South East Asia and USA. CONCLUSIONS: This study reported the successful isolation of local type I and type II FCoV evident with formation of cytopathic effects in two types of cell cultures namely the CrFK and Fcwf-4 , where the later cells being more permissive. However, the RT-PCR assay is more sensitive in detecting the antigen in suspected samples as compared to virus isolation in cell culture. The present study indicated that type I FCoV is more prevalent among cats in Malaysia.",2012 Nov 21,"['Amer, Alazawy', 'Siti Suri, Arshad', 'Abdul Rahman, Omar', 'Mohd, Hair Bejo', 'Faruku, Bande', 'Saeed, Sharif', 'Tengku Azmi, Tengku Ibrahim']",Virol J,,,True
2d9482a26d740c255bf3108d1c628e97fae3cc7a,PMC,Complete Genome Analysis of Canine Respiratory Coronavirus,http://dx.doi.org/10.1128/genomeA.00093-12,PMC3569343,23405345,CC BY,"The canine respiratory coronavirus (CRCoV) K37 strain of the family Coronaviridae, group 2, was isolated in South Korea. Its genome was analyzed by nucleotide sequencing and was determined to have 31,029 bp. The small open reading frames situated between the spike and envelope genes of most of the CRCoV strains (except the CRCoV 4180 strain) were found to encode three nonstructural proteins (4.9 kDa, 2.7 kDa, and 12.8 kDa), while those of bovine coronavirus (BCoV) encode another three nonstructural proteins (4.9 kDa, 4.8 kDa, and 12.7 kDa) and those of a recently isolated bovine respiratory coronavirus (BRCoV) were found to encode only two nonstructural proteins (4.9 kDa and 12.7 kDa). The differences in the genes encoding these small nonstructural proteins may be associated with the emergence of highly similar viruses in different hosts.",2013 Jan 31,"['Lim, Seong-in', 'Choi, Sarah', 'Lim, Ji-Ae', 'Jeoung, Hye-Young', 'Song, Jae-Young', 'dela Pena, R. C.', 'An, Dong-Jun']",Genome Announc,,,True
782bdb3d8291de8f51c2816a707833c165c3ea35,PMC,"Genome sequences published outside of Standards in Genomic Sciences, October - November 2012",http://dx.doi.org/10.4056/sigs.3597227,PMC3569392,,CC BY,"The purpose of this table is to provide the community with a citable record of publications of ongoing genome sequencing projects that have led to a publication in the scientific literature. While our goal is to make the list complete, there is no guarantee that we may have omitted one or more publications appearing in this time frame. Readers and authors who wish to have publications added to subsequent versions of this list are invited to provide the bibliographic data for such references to the SIGS editorial office.",2012 Dec 12,"['Nelson, Oranmiyan W.', 'Garrity, George M.']",Stand Genomic Sci,,,True
9b56c6e647ccdb8b5d534c0689a71efb7728a311,PMC,Binding of DC-SIGN to the Hemagglutinin of Influenza A Viruses Supports Virus Replication in DC-SIGN Expressing Cells,http://dx.doi.org/10.1371/journal.pone.0056164,PMC3570528,23424649,CC BY,"Dendritic cells express lectins receptors, like DC-SIGN, which allow these cells to sense glycans that are present on various bacterial and viral pathogens. Interaction of DC-SIGN with carbohydrate moieties induces maturation of dendritic cells and promotes endocytosis of pathogens which is an important property of these professional antigen presenting cells. Uptake of pathogens by dendritic cells may lead to cross-presentation of antigens or infection of these cells, which ultimately results in activation of virus-specific T cells in draining lymph nodes. Little is known about the interaction of DC-SIGN with influenza A viruses. Here we show that a virus with a non-functional receptor binding site in its hemagglutinin, can replicate in cells expressing DC-SIGN. Also in the absence of sialic acids, which is the receptor for influenza A viruses, these viruses replicate in DC-SIGN expressing cells including human dendritic cells. Furthermore, the efficiency of DC-SIGN mediated infection is dependent on the extent of glycosylation of the viral hemagglutinin.",2013 Feb 12,"['Hillaire, Marine L. B.', 'Nieuwkoop, Nella J.', 'Boon, Adrianus C. M.', 'de Mutsert, Gerrie', 'Vogelzang-van Trierum, Stella E.', 'Fouchier, Ron A. M.', 'Osterhaus, Albert D. M. E.', 'Rimmelzwaan, Guus F.']",PLoS One,,,True
e172007ec7885b58e7a14be7459e0250ac47ba52,PMC,"Genome sequences published outside of Standards in Genomic Sciences, July - October 2012",http://dx.doi.org/10.4056/sigs.3416907,PMC3570808,,CC BY,"The purpose of this table is to provide the community with a citable record of publications of ongoing genome sequencing projects that have led to a publication in the scientific literature. While our goal is to make the list complete, there is no guarantee that we may have omitted one or more publications appearing in this time frame. Readers and authors who wish to have publications added to subsequent versions of this list are invited to provide the bibliographic data for such references to the SIGS editorial office.",2012 Oct 10,"['Nelson, Oranmiyan W.', 'Garrity, George M.']",Stand Genomic Sci,,,True
4f380911a4cf1b78dce1c016c1c0cc2f95a15f7b,PMC,Influenza Aerosols in UK Hospitals during the H1N1 (2009) Pandemic – The Risk of Aerosol Generation during Medical Procedures,http://dx.doi.org/10.1371/journal.pone.0056278,PMC3571988,23418548,CC BY,"BACKGROUND: Nosocomial infection of health-care workers (HCWs) during outbreaks of respiratory infections (e.g. Influenza A H1N1 (2009)) is a significant concern for public health policy makers. World Health Organization (WHO)-defined ‘aerosol generating procedures’ (AGPs) are thought to increase the risk of aerosol transmission to HCWs, but there are presently insufficient data to quantify risk accurately or establish a hierarchy of risk-prone procedures. METHODOLOGY/PRINCIPAL FINDINGS: This study measured the amount of H1N1 (2009) RNA in aerosols in the vicinity of H1N1 positive patients undergoing AGPs to help quantify the potential risk of transmission to HCWs. There were 99 sampling occasions (windows) producing a total of 198 May stages for analysis in the size ranges 0.86–7.3 µm. Considering stages 2 (4–7.3 µm) and 3 (0.86–4 µm) as comprising one sample, viral RNA was detected in 14 (14.1%) air samples from 10 (25.6%) patients. Twenty three air samples were collected while potential AGPs were being performed of which 6 (26.1%) contained viral RNA; in contrast, 76 May samples were collected when no WHO 2009 defined AGP was being performed of which 8 (10.5%) contained viral RNA (unadjusted OR = 2.84 (95% CI 1.11–7.24) adjusted OR = 4.31 (0.83–22.5)). CONCLUSIONS/SIGNIFICANCE: With our small sample size we found that AGPs do not significantly increase the probability of sampling an H1N1 (2009) positive aerosol (OR (95% CI) = 4.31 (0.83–22.5). Although the probability of detecting positive H1N1 (2009) positive aerosols when performing various AGPs on intensive care patients above the baseline rate (i.e. in the absence of AGPs) did not reach significance, there was a trend towards hierarchy of AGPs, placing bronchoscopy and respiratory and airway suctioning above baseline (background) values. Further, larger studies are required but these preliminary findings may be of benefit to infection control teams.",2013 Feb 13,"['Thompson, Katy-Anne', 'Pappachan, John V.', 'Bennett, Allan M.', 'Mittal, Himanshu', 'Macken, Susan', 'Dove, Brian K.', 'Nguyen-Van-Tam, Jonathan S.', 'Copley, Vicky R.', 'O’Brien, Sarah', 'Hoffman, Peter', 'Parks, Simon', 'Bentley, Andrew', 'Isalska, Barbara', 'Thomson, Gail', None]",PLoS One,,,True
1bebd833b3535712b5d13f9ed985e3491d3c96c8,PMC,Chloroquine Inhibits Dengue Virus Type 2 Replication in Vero Cells but Not in C6/36 Cells,http://dx.doi.org/10.1155/2013/282734,PMC3572654,23431254,CC BY,"Dengue viruses are the most important arthropod-borne viruses in terms of morbidity and mortality in the world. Since there is no dengue vaccine available for human use, we have set out to investigate the use of chloroquine as an antiviral drug against dengue. Chloroquine, an amine acidotropic drug known to affect intracellular exocytic pathways by increasing endosomal pH, was used in the in vitro treatment of Vero and C6/36 cells infected with dengue virus type 2 (DENV-2). Real-time RT-PCR and plaque assays were used to quantify the DENV-2 load in infected Vero and C6/36 cells after chloroquine treatment. Our results showed that a dose of 50 μg/ml of chloroquine was not toxic to the cells and induced a statistically significant inhibition of virus production in infected Vero cells when compared to untreated cells. In C6/36 cells, chloroquine does not induce a statistically significant difference in viral replication when compared to untreated cells, showing that this virus uses an unlikely pathway of penetration in these cells, and results were also confirmed by the plaque assay (PFU). These data suggest that the inhibition of virus infection induced by chloroquine is due to interference with acidic vesicles in mammalian cells.",2013 Jan 31,"['Farias, Kleber Juvenal Silva', 'Machado, Paula Renata Lima', 'da Fonseca, Benedito Antônio Lopes']",ScientificWorldJournal,,,True
da284bc0d5d74602b201a169fb7a0392eef5b6f8,PMC,A novel double antibody sandwich-lateral flow immunoassay for the rapid and simple detection of hepatitis C virus,http://dx.doi.org/10.3892/ijmm.2012.1121,PMC3573733,22960954,CC BY,"The objective of this study was to screen for antigens of the hepatitis C virus (HCV) to establish a new double antibody sandwich-lateral flow immunoassay (DAS-LFIA) method for testing the presence of anti-HCV antibodies in human serum or plasma. A series of different recombinant HCV proteins in Escherichia coli cells were constructed, expressed, purified and the new DAS-LFIA strip was developed. The sensitivity and specificity of new the DAS-LFIA strip were evaluated by detecting 23 HCV-positive sera, a set of quality control references for anti-HCV detection that contain known amounts of anti-HCV antibodies, and 8 HCV-negative sera. A total of 300 clinical serum samples was examined by both the new DAS-LFIA strip and enzyme-linked immunosorbent assay (ELISA). Data were analyzed using SPSS 11.5 software. The sensitivity and specificity of the new DAS-LFIA strip were 100%. The lowest test line of the HCV DAS-LFIA strips was 2 NCU/ml. Additionally, the concordance between the new DAS-LFIA strip and ELISA methods was 94.33%. In conclusion, our new testing method is rapid, simple, sensitive and specifically detects the presence of anti-HCV antibodies in human serum or plasma. Therefore, it may be used for monitoring HCV.",2012 Nov 6,"['XIANG, TINGXIU', 'JIANG, ZHENG', 'ZHENG, JIAN', 'LO, CHAOYU', 'TSOU, HARRY', 'REN, GUOSHENG', 'ZHANG, JUN', 'HUANG, AILONG', 'LAI, GUOQI']",Int J Mol Med,,,True
70fefc54856d09f01cb983932a860dc4dacb9f46,PMC,Curcumin inhibits HCV replication by induction of heme oxygenase-1 and suppression of AKT,http://dx.doi.org/10.3892/ijmm.2012.1096,PMC3573749,22922731,CC BY,"Although hepatitis C virus (HCV) affects approximately 130–170 million people worldwide, no vaccines are available. HCV is an important cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, leading to the need for liver transplantation. In this study, curcumin, a constituent used in traditional Chinese medicine, has been evaluated for its anti-HCV activity and mechanism, using a human hepatoma cell line containing the HCV genotype 1b subgenomic replicon. Below the concentration of 20% cytotoxicity, curcumin dose-dependently inhibited HCV replication by luciferase reporter gene assay, HCV RNA detection and HCV protein analysis. Under the same conditions, curcumin also dose-dependently induced heme oxygenase-1 with the highest induction at 24 h. Hemin, a heme oxygenase-1 inducer, also inhibited HCV protein expression in a dose-dependent manner. The knockdown of heme oxygenase-1 partially reversed the curcumin-inhibited HCV protein expression. In addition to the heme oxygenase-1 induction, signaling molecule activities of AKT, extracellular signal-regulated kinases (ERK) and nuclear factor-κB (NF-κB) were inhibited by curcumin. Using specific inhibitors of PI3K-AKT, MEK-ERK and NF-κB, the results suggested that only PI3K-AKT inhibition is positively involved in curcumin-inhibited HCV replication. Inhibition of ERK and NF-κB was likely to promote HCV protein expression. In summary, curcumin inhibited HCV replication by heme oxygenase-1 induction and AKT pathway inhibition. Although curcumin also inhibits ERK and NF-κB activities, it slightly increased the HCV protein expression. This result may provide information when curcumin is used as an adjuvant in anti-HCV therapy.",2012 Nov 20,"['CHEN, MING-HO', 'LEE, MING-YANG', 'CHUANG, JING-JING', 'LI, YI-ZHEN', 'NING, SIN-TZU', 'CHEN, JUNG-CHOU', 'LIU, YI-WEN']",Int J Mol Med,,,True
a63e10c460821fd20aa9f58b6d7f4634b05b16ce,PMC,The role of infections and coinfections with newly identified and emerging respiratory viruses in children,http://dx.doi.org/10.1186/1743-422X-9-247,PMC3573994,23102237,CC BY,"Acute respiratory infections are a major cause of morbidity in children both in developed and developing countries. A wide range of respiratory viruses, including respiratory syncytial virus (RSV), influenza A and B viruses, parainfluenza viruses (PIVs), adenovirus, rhinovirus (HRV), have repeatedly been detected in acute lower respiratory tract infections (LRTI) in children in the past decades. However, in the last ten years thanks to progress in molecular technologies, newly discovered viruses have been identified including human Metapneumovirus (hMPV), coronaviruses NL63 (HcoV-NL63) and HKU1 (HcoV-HKU1), human Bocavirus (HBoV), new enterovirus (HEV), parechovirus (HpeV) and rhinovirus (HRV) strains, polyomaviruses WU (WUPyV) and KI (KIPyV) and the pandemic H1N1v influenza A virus. These discoveries have heavily modified previous knowledge on respiratory infections mainly highlighting that pediatric population is exposed to a variety of viruses with similar seasonal patterns. In this context establishing a causal link between a newly identified virus and the disease as well as an association between mixed infections and an increase in disease severity can be challenging. This review will present an overview of newly recognized as well as the main emerging respiratory viruses and seek to focus on the their contribution to infection and co-infection in LRTIs in childhood.",2012 Oct 27,"['Debiaggi, Maurizia', 'Canducci, Filippo', 'Ceresola, Elisa Rita', 'Clementi, Massimo']",Virol J,,,True
e05c7165987a9b706d1ab55ebb210bd571a59e5a,PMC,Discovery and antitumor activities of constituents from Cyrtomium fortumei (J.) Smith rhizomes,http://dx.doi.org/10.1186/1752-153X-7-24,PMC3574041,23379693,CC BY,"BACKGROUND: Cyrtomium fortumei (J.) Smith is an important Chinese herbal medicine because of its biological functions. However, systematic and comprehensive studies on the phytochemicals from Cyrtomium fortumei (J.) Smith and their bioactivity are limited. RESULTS: Using the bioassay-guided technique, the ethyl acetate and n-BuOH extracts of the rhizomes of Cyrtomium fortumei (J.) Smith were shown to exhibit good antitumor activities, consequently leading to the isolation of 23 compounds. All compounds were isolated from the plant for the first time. The inhibitory activities of these compounds were investigated on tumor cells MGC-803, PC3, and A375 in vitro by MTT (thiazolyl blue tetrazolium bromide) assay, and the results showed that pimpinellin (3) had potent cytotoxic activities against the three cell lines, with the IC(50) values of 14.4 ± 0.3 μM, 20.4 ± 0.5 μM, and 29.2 ± 0.6 μM, respectively. The mechanism of the antitumor action indicated that pimpinellin inhibited the growth of MGC-803 cells via the induction of tumor cell apoptosis, with apoptosis ratio of 27.44% after 72 h of treatment at 20 μM. CONCLUSIONS: This study suggests that most of the compounds from the roots of Cyrtomium fortumei (J.) Smith could inhibit the growth of human carcinoma cells. Moreover, pimpinellin inhibited the growth of tumor cells via the induction of tumor cell apoptosis.",2013 Feb 4,"['Yang, Shengjie', 'Liu, Mingchuan', 'Liang, Na', 'Zhao, Qi', 'Zhang, Yuping', 'Xue, Wei', 'Yang, Song']",Chem Cent J,,,True
4152ae12ac49d157a290281842bce9e9d16096a7,PMC,Residue analysis of a CTL epitope of SARS-CoV spike protein by IFN-gamma production and bioinformatics prediction,http://dx.doi.org/10.1186/1471-2172-13-50,PMC3575293,22963340,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by the novel coronavirus SARS-CoV. The T cell epitopes of the SARS CoV spike protein are well known, but no systematic evaluation of the functional and structural roles of each residue has been reported for these antigenic epitopes. Analysis of the functional importance of side-chains by mutational study may exaggerate the effect by imposing a structural disturbance or an unusual steric, electrostatic or hydrophobic interaction. RESULTS: We demonstrated that N50 could induce significant IFN-gamma response from SARS-CoV S DNA immunized mice splenocytes by the means of ELISA, ELISPOT and FACS. Moreover, S366-374 was predicted to be an optimal epitope by bioinformatics tools: ANN, SMM, ARB and BIMAS, and confirmed by IFN-gamma response induced by a series of S358-374-derived peptides. Furthermore, each of S366-374 was replaced by alanine (A), lysine (K) or aspartic acid (D), respectively. ANN was used to estimate the binding affinity of single S366-374 mutants to H-2 Kd. Y367 and L374 were predicated to possess the most important role in peptide binding. Additionally, these one residue mutated peptides were synthesized, and IFN-gamma production induced by G368, V369, A371, T372 and K373 mutated S366-374 were decreased obviously. CONCLUSIONS: We demonstrated that S366-374 is an optimal H-2 Kd CTL epitope in the SARS CoV S protein. Moreover, Y367, S370, and L374 are anchors in the epitope, while C366, G368, V369, A371, T372, and K373 may directly interact with TCR on the surface of CD8-T cells.",2012 Sep 10,"['Huang, Jun', 'Cao, Yingnan', 'Bu, Xianzhang', 'Wu, Changyou']",BMC Immunol,,,True
ae79fbbd7e6130c0d5b451617260a7e63bda79e4,PMC,Lessons learned from a double-blind randomised placebo-controlled study with a iota-carrageenan nasal spray as medical device in children with acute symptoms of common cold,http://dx.doi.org/10.1186/1472-6882-12-147,PMC3575307,22950667,CC BY,"BACKGROUND: Common cold is caused by a variety of respiratory viruses. The prevalence in children is high, and it potentially contributes to significant morbidity. Iota-carragenan, a polymer derived from red seaweed, has reduced viral load in nasal secretions and alleviated symptoms in adults with common cold. METHODS: We have assessed the antiviral and therapeutic activity of a nasal spray containing iota-carrageenan in children with acute symptoms of common cold. A cohort of 153 children between 1–18 years (mean age 5 years), displaying acute symptoms of common cold were randomly assigned to treatment with a nasal spray containing iota-carrageenan (0.12%) as verum or 0.9% sodium chloride solution as placebo for seven days. Symptoms of common cold were recorded and the viral load of respiratory viruses in nasal secretions was determined at two consecutive visits. RESULTS: The results of the present study showed no significant difference between the iota carrageenan and the placebo group on the mean of TSS between study days 2–7. Secondary endpoints, such as reduced time to clearance of disease (7.6 vs 9.4 days; p = 0.038), reduction of viral load (p = 0.026), and lower incidence of secondary infections with other respiratory viruses (p = 0.046) indicated beneficial effects of iota-carrageenan in this population. The treatment was safe and well tolerated, with less side effects observed in the verum group compared to placebo. CONCLUSION: In this study iota-carrageenan did not alleviate symptoms in children with acute symptoms of common cold, but significantly reduced viral load in nasal secretions that may have important implications for future studies. TRIAL REGISTRATION: ISRCTN52519535, http://www.controlled-trials.com/ISRCTN52519535/",2012 Sep 5,"['Fazekas, Tamas', 'Eickhoff, Philipp', 'Pruckner, Nathalie', 'Vollnhofer, Georg', 'Fischmeister, Gustav', 'Diakos, Christopher', 'Rauch, Margit', 'Verdianz, Maria', 'Zoubek, Andreas', 'Gadner, Helmut', 'Lion, Thomas']",BMC Complement Altern Med,,,True
1e863993819f87abe5cee255ccb97d623838542a,PMC,A novel bocavirus in canine liver,http://dx.doi.org/10.1186/1743-422X-10-54,PMC3577433,23402347,CC BY,"BACKGROUND: Bocaviruses are classified as a genus within the Parvoviridae family of single-stranded DNA viruses and are pathogenic in some mammalian species. Two species have been previously reported in dogs, minute virus of canines (MVC), associated with neonatal diseases and fertility disorders; and Canine bocavirus (CBoV), associated with respiratory disease. FINDINGS: In this study using deep sequencing of enriched viral particles from the liver of a dog with severe hemorrhagic gastroenteritis, necrotizing vasculitis, granulomatous lymphadenitis and anuric renal failure, we identified and characterized a novel bocavirus we named Canine bocavirus 3 (CnBoV3). The three major ORFs of CnBoV3 (NS1, NP1 and VP1) shared less than 60% aa identity with those of other bocaviruses qualifying it as a novel species based on ICTV criteria. Inverse PCR showed the presence of concatemerized or circular forms of the genome in liver. CONCLUSIONS: We genetically characterized a bocavirus in a dog liver that is highly distinct from prior canine bocaviruses found in respiratory and fecal samples. Its role in this animal’s complex disease remains to be determined.",2013 Feb 13,"['Li, Linlin', 'Pesavento, Patricia A', 'Leutenegger, Christian M', 'Estrada, Marko', 'Coffey, Lark L', 'Naccache, Samia N', 'Samayoa, Erik', 'Chiu, Charles', 'Qiu, Jianming', 'Wang, Chunlin', 'Deng, Xutao', 'Delwart, Eric']",Virol J,,,True
e3090e4e8baa6df559f0299519ad77821a09f873,PMC,"Modeling the impact of air, sea, and land travel restrictions supplemented by other interventions on the emergence of a new influenza pandemic virus",http://dx.doi.org/10.1186/1471-2334-12-309,PMC3577649,23157818,CC BY,"BACKGROUND: During the early stages of a new influenza pandemic, travel restriction is an immediate and non-pharmaceutical means of retarding incidence growth. It extends the time frame of effective mitigation, especially when the characteristics of the emerging virus are unknown. In the present study, we used the 2009 influenza A pandemic as a case study to evaluate the impact of regulating air, sea, and land transport. Other government strategies, namely, antivirals and hospitalizations, were also evaluated. METHODS: Hong Kong arrivals from 44 countries via air, sea, and land transports were imported into a discrete stochastic Susceptible, Exposed, Infectious and Recovered (SEIR) host-flow model. The model allowed a number of latent and infectious cases to pass the border, which constitutes a source of local disease transmission. We also modeled antiviral and hospitalization prevention strategies to compare the effectiveness of these control measures. Baseline reproduction rate was estimated from routine surveillance data. RESULTS: Regarding air travel, the main route connected to the influenza source area should be targeted for travel restrictions; imposing a 99% air travel restriction delayed the epidemic peak by up to two weeks. Once the pandemic was established in China, the strong land connection between Hong Kong and China rendered Hong Kong vulnerable. Antivirals and hospitalization were found to be more effective on attack rate reductions than travel restrictions. Combined strategies (with 99% restriction on all transport modes) deferred the peak for long enough to establish a vaccination program. CONCLUSION: The findings will assist policy-makers with decisions on handling similar future pandemics. We also suggest regulating the extent of restriction and the transport mode, once restriction has been deemed necessary for pandemic control. Although travel restrictions have yet to gain social acceptance, they allow time for mitigation response when a new and highly intrusive virus emerges.",2012 Nov 19,"['Chong, Ka Chun', 'Ying Zee, Benny Chung']",BMC Infect Dis,,,True
9b4d56c6c289c7f86b4f01b1b5569ae7e2bf6920,PMC,"Modeling the impact of air, sea, and land travel restrictions supplemented by other interventions on the emergence of a new influenza pandemic virus",http://dx.doi.org/10.1186/1471-2334-12-309,PMC3577649,23157818,CC BY,"BACKGROUND: During the early stages of a new influenza pandemic, travel restriction is an immediate and non-pharmaceutical means of retarding incidence growth. It extends the time frame of effective mitigation, especially when the characteristics of the emerging virus are unknown. In the present study, we used the 2009 influenza A pandemic as a case study to evaluate the impact of regulating air, sea, and land transport. Other government strategies, namely, antivirals and hospitalizations, were also evaluated. METHODS: Hong Kong arrivals from 44 countries via air, sea, and land transports were imported into a discrete stochastic Susceptible, Exposed, Infectious and Recovered (SEIR) host-flow model. The model allowed a number of latent and infectious cases to pass the border, which constitutes a source of local disease transmission. We also modeled antiviral and hospitalization prevention strategies to compare the effectiveness of these control measures. Baseline reproduction rate was estimated from routine surveillance data. RESULTS: Regarding air travel, the main route connected to the influenza source area should be targeted for travel restrictions; imposing a 99% air travel restriction delayed the epidemic peak by up to two weeks. Once the pandemic was established in China, the strong land connection between Hong Kong and China rendered Hong Kong vulnerable. Antivirals and hospitalization were found to be more effective on attack rate reductions than travel restrictions. Combined strategies (with 99% restriction on all transport modes) deferred the peak for long enough to establish a vaccination program. CONCLUSION: The findings will assist policy-makers with decisions on handling similar future pandemics. We also suggest regulating the extent of restriction and the transport mode, once restriction has been deemed necessary for pandemic control. Although travel restrictions have yet to gain social acceptance, they allow time for mitigation response when a new and highly intrusive virus emerges.",2012 Nov 19,"['Chong, Ka Chun', 'Ying Zee, Benny Chung']",BMC Infect Dis,,,True
db5d4d312d002e6bdc87f433d1ad118681167016,PMC,Detection of infectious bronchitis virus serotypes by reverse transcription polymerase chain reaction in broiler chickens,http://dx.doi.org/10.1186/2193-1801-2-36,PMC3579474,23450039,CC BY,"Infectious bronchitis (IB) is a highly contagious disease of the respiratory and urogenital tract of chickens, caused by infectious bronchitis virus (IBV), a member of the family Coronaviridae. The disease is common throughout the world where chickens are produced commercially. PCR on reverse transcribed RNA is a potent technique for the detection of IBV. In comparison with classical detection methods, PCR-based techniques are both sensitive and fast. Dozens of serotypes and genotypes of IBV have been detected, and many more will surely be reported in future. This research was conducted to identify the infectious bronchitis virus with group specific primers of avian Coronaviruses in Zabol, southeast of Iran. Tracheal swabs were collected from eleven commercial broiler flocks and these swabs were used for RNA extraction. General primers included XCE2+ and XCE2- that amplify all IBV serotypes were used. Primers MCE1+, BCE1+ and DCE1+ was used to amplifying the specific nucleotide sequence of Massachusetts, 4/91 and D274 serotypes, respectively. The results of this study showed that 36.36% of the sampled flocks were positive to IBV by RT-PCR. Moreover, the Massachusetts was the identified serotype of infectious bronchitis virus. The results provide the first molecular evidence for the presence of infectious bronchitis virus and Massachusetts serotype in Zabol. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-36) contains supplementary material, which is available to authorized users.",2013 Jan 31,"['Jahantigh, Mohammad', 'Salari, Saeed', 'Hedayati, Mahdi']",Springerplus,,,True
b293146d54c66eef361bc16cc69f793f46f88f1b,PMC,Tracking and visualization of space-time activities for a micro-scale flu transmission study,http://dx.doi.org/10.1186/1476-072X-12-6,PMC3579692,23388060,CC BY,"BACKGROUND: Infectious diseases pose increasing threats to public health with increasing population density and more and more sophisticated social networks. While efforts continue in studying the large scale dissemination of contagious diseases, individual-based activity and behaviour study benefits not only disease transmission modelling but also the control, containment, and prevention decision making at the local scale. The potential for using tracking technologies to capture detailed space-time trajectories and model individual behaviour is increasing rapidly, as technological advances enable the manufacture of small, lightweight, highly sensitive, and affordable receivers and the routine use of location-aware devices has become widespread (e.g., smart cellular phones). The use of low-cost tracking devices in medical research has also been proved effective by more and more studies. This study describes the use of tracking devices to collect data of space-time trajectories and the spatiotemporal processing of such data to facilitate micro-scale flu transmission study. We also reports preliminary findings on activity patterns related to chances of influenza infection in a pilot study. METHODS: Specifically, this study employed A-GPS tracking devices to collect data on a university campus. Spatiotemporal processing was conducted for data cleaning and segmentation. Processed data was validated with traditional activity diaries. The A-GPS data set was then used for visual explorations including density surface visualization and connection analysis to examine space-time activity patterns in relation to chances of influenza infection. RESULTS: When compared to diary data, the segmented tracking data demonstrated to be an effective alternative and showed greater accuracies in time as well as the details of routes taken by participants. A comparison of space-time activity patterns between participants who caught seasonal influenza and those who did not revealed interesting patterns. CONCLUSIONS: This study proved that tracking technology an effective technique for obtaining data for micro-scale influenza transmission research. The findings revealed micro-scale transmission hotspots on a university campus and provided insights for local control and prevention strategies.",2013 Feb 7,"['Qi, Feng', 'Du, Fei']",Int J Health Geogr,,,True
426d73371e7f29a3d046687525d416f68708f643,PMC,Persistent digestive disorders in the tropics: causative infectious pathogens and reference diagnostic tests,http://dx.doi.org/10.1186/1471-2334-13-37,PMC3579720,23347408,CC BY,"BACKGROUND: Persistent digestive disorders account for considerable disease burden in the tropics. Despite advances in understanding acute gastrointestinal infections, important issues concerning epidemiology, diagnosis, treatment and control of most persistent digestive symptomatologies remain to be elucidated. Helminths and intestinal protozoa are considered to play major roles, but the full extent of the aetiologic spectrum is still unclear. We provide an overview of pathogens causing digestive disorders in the tropics and evaluate available reference tests. METHODS: We searched the literature to identify pathogens that might give rise to persistent diarrhoea, chronic abdominal pain and/or blood in the stool. We reviewed existing laboratory diagnostic methods for each pathogen and stratified them by (i) microscopy; (ii) culture techniques; (iii) immunological tests; and (iv) molecular methods. Pathogen-specific reference tests providing highest diagnostic accuracy are described in greater detail. RESULTS: Over 30 pathogens may cause persistent digestive disorders. Bacteria, viruses and parasites are important aetiologic agents of acute and long-lasting symptomatologies. An integrated approach, consisting of stool culture, microscopy and/or specific immunological techniques for toxin, antigen and antibody detection, is required for accurate diagnosis of bacteria and parasites. Molecular techniques are essential for sensitive diagnosis of many viruses, bacteria and intestinal protozoa, and are increasingly utilised as adjuncts for helminth identification. CONCLUSIONS: Diagnosis of the broad spectrum of intestinal pathogens is often cumbersome. There is a need for rapid diagnostic tests that are simple and affordable for resource-constrained settings, so that the management of patients suffering from persistent digestive disorders can be improved.",2013 Jan 24,"['Becker, Sören L', 'Vogt, Jürg', 'Knopp, Stefanie', 'Panning, Marcus', 'Warhurst, David C', 'Polman, Katja', 'Marti, Hanspeter', 'von Müller, Lutz', 'Yansouni, Cedric P', 'Jacobs, Jan', 'Bottieau, Emmanuel', 'Sacko, Moussa', 'Rijal, Suman', 'Meyanti, Fransiska', 'Miles, Michael A', 'Boelaert, Marleen', 'Lutumba, Pascal', 'van Lieshout, Lisette', 'N’Goran, Eliézer K', 'Chappuis, François', 'Utzinger, Jürg']",BMC Infect Dis,,,True
0414c8763c6ec295be60d86698ec3a76e981e54f,PMC,Synthetic Genomics and Synthetic Biology Applications Between Hopes and Concerns,http://dx.doi.org/10.2174/1389202911314010003,PMC3580775,23997647,CC BY,"New organisms and biological systems designed to satisfy human needs are among the aims of synthetic genomics and synthetic biology. Synthetic biology seeks to model and construct biological components, functions and organisms that do not exist in nature or to redesign existing biological systems to perform new functions. Synthetic genomics, on the other hand, encompasses technologies for the generation of chemically-synthesized whole genomes or larger parts of genomes, allowing to simultaneously engineer a myriad of changes to the genetic material of organisms. Engineering complex functions or new organisms in synthetic biology are thus progressively becoming dependent on and converging with synthetic genomics. While applications from both areas have been predicted to offer great benefits by making possible new drugs, renewable chemicals or clean energy, they have also given rise to concerns about new safety, environmental and socio-economic risks – stirring an increasingly polarizing debate. Here we intend to provide an overview on recent progress in biomedical and biotechnological applications of synthetic genomics and synthetic biology as well as on arguments and evidence related to their possible benefits, risks and governance implications.",2013 Mar,"['König, Harald', 'Frank, Daniel', 'Heil, Reinhard', 'Coenen, Christopher']",Curr Genomics,,,True
a33e3ade1bf2a47195051d6d458baa2001ab72a5,PMC,Prescription Surveillance and Polymerase Chain Reaction Testing to Identify Pathogens during Outbreaks of Infection,http://dx.doi.org/10.1155/2013/746053,PMC3581269,23509772,CC BY,"Syndromic surveillance, including prescription surveillance, offers a rapid method for the early detection of agents of bioterrorism and emerging infectious diseases. However, it has the disadvantage of not considering definitive diagnoses. Here, we attempted to definitively diagnose pathogens using polymerase chain reaction (PCR) immediately after the prescription surveillance system detected an outbreak. Specimens were collected from 50 patients with respiratory infections. PCR was used to identify the pathogens, which included 14 types of common respiratory viruses and Mycoplasma pneumoniae. Infectious agents including M. pneumoniae, respiratory syncytial virus (RSV), rhinovirus, enterovirus, and parainfluenza virus were detected in 54% of patients. For the rapid RSV diagnosis kit, sensitivity was 80% and specificity was 85%. For the rapid adenovirus diagnosis kit, no positive results were obtained; therefore, sensitivity could not be calculated and specificity was 100%. Many patients were found to be treated for upper respiratory tract infections without the diagnosis of a specific pathogen. In Japan, an outbreak of M. pneumoniae infection began in 2011, and our results suggested that this outbreak may have included false-positive cases. By combining syndromic surveillance and PCR, we were able to rapidly and accurately identify causative pathogens during a recent respiratory infection outbreak.",2013 Feb 7,"['Sugiura, Hiroaki', 'Fujimoto, Tsuguto', 'Sugawara, Tamie', 'Hanaoka, Nozomu', 'Konagaya, Masami', 'Kikuchi, Kiyoshi', 'Hanada, Eisuke', 'Okabe, Nobuhiko', 'Ohkusa, Yasushi']",Biomed Res Int,,,True
ff76f00bf68006acc97c8720dd4f11e69d17c272,PMC,Glucocorticosteroids as Dengue Therapeutics: Resolving Clinical Observations With a Primary Human Macrophage Model,http://dx.doi.org/10.1093/cid/cis1048,PMC3582356,23243185,CC BY,,2013 Mar 15,"['Sayce, Andrew C.', 'Miller, Joanna L.', 'Zitzmann, Nicole']",Clin Infect Dis,,,True
3d3886831b542dfc9d1b6428ac48d96589d0ae61,PMC,The R0 package: a toolbox to estimate reproduction numbers for epidemic outbreaks,http://dx.doi.org/10.1186/1472-6947-12-147,PMC3582628,23249562,CC BY,"BACKGROUND: Several generic methods have been proposed to estimate transmission parameters during an outbreak, especially the reproduction number. However, as of today, no dedicated software exists that implements these methods and allow comparisons. RESULTS: A review of generic methods used to estimate transmissibility parameters during outbreaks was carried out. Most methods used the epidemic curve and the generation time distribution. Two categories of methods were available: those estimating the initial reproduction number, and those estimating a time dependent reproduction number. We implemented five methods as an R library, developed sensitivity analysis tools for each method and provided numerical illustrations of their use. A comparison of the performance of the different methods on simulated datasets is reported. CONCLUSIONS: This software package allows a standardized and extensible approach to the estimation of the reproduction number and generation interval distribution from epidemic curves.",2012 Dec 18,"['Obadia, Thomas', 'Haneef, Romana', 'Boëlle, Pierre-Yves']",BMC Med Inform Decis Mak,,,True
dc352893117f666477e7cf7c8c614bdf60592178,PMC,Enhancing Bioaerosol Sampling by Andersen Impactors Using Mineral-Oil-Spread Agar Plate,http://dx.doi.org/10.1371/journal.pone.0056896,PMC3584084,23460818,CC BY,"As a bioaerosol sampling standard, Andersen type impactor is widely used since its invention in 1950s, including the investigation of the anthrax attacks in the United States in 2001. However, its related problems such as impaction and desiccation stress as well as particle bounce have not been solved. Here, we improved its biological collection efficiencies by plating a mineral oil layer (100 µL) onto the agar plate. An Andersen six-stage sampler and a BioStage impactor were tested with mineral-oil-spread agar plates in collecting indoor and outdoor bacterial and fungal aerosols. The effects of sampling times (5, 10 and 20 min) were also studied using the BioStage impactor when sampling environmental bioaerosols as well as aerosolized Bacillus subtilis (G+) and Escherichia coli (G-). In addition, particle bounce reduction by mineral-oil-plate was also investigated using an optical particle counter (OPC). Experimental results revealed that use of mineral-oil-spread agar plate can substantially enhance culturable bioaerosol recoveries by Andersen type impactors (p-values<0.05). The recovery enhancement was shown to depend on bioaerosol size, type, sampling time and environment. In general, more enhancements (extra 20%) were observed for last stage of the Andersen six-stage samplers compared to the BioStage impactor for 10 min sampling. When sampling aerosolized B. subtilis, E. coli and environmental aerosols, the enhancement was shown to increase with increasing sampling time, ranging from 50% increase at 5 min to ∼100% at 20 min. OPC results indicated that use of mineral oil can effectively reduce the particle bounce with an average of 66% for 10 min sampling. Our work suggests that enhancements for fungal aerosols were primarily attributed to the reduced impaction stress, while for bacterial aerosols reduced impaction, desiccation and particle bounce played major roles. The developed technology can readily enhance the agar-based techniques including those high volume portable samplers for bioaerosol monitoring.",2013 Feb 27,"['Xu, Zhenqiang', 'Wei, Kai', 'Wu, Yan', 'Shen, Fangxia', 'Chen, Qi', 'Li, Mingzhen', 'Yao, Maosheng']",PLoS One,,,True
ebb05424e38f5e17460ce65e2ccd5a7ad4f73b42,PMC,Estimation of the National Disease Burden of Influenza-Associated Severe Acute Respiratory Illness in Kenya and Guatemala: A Novel Methodology,http://dx.doi.org/10.1371/journal.pone.0056882,PMC3584100,23573177,CC0,"BACKGROUND: Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden. METHODS AND FINDINGS: This method begins with calculating the hospitalized severe acute respiratory illness (SARI) incidence for children <5 years old and persons ≥5 years old from population-based surveillance in one province. This base rate of SARI is then adjusted for each province based on the prevalence of risk factors and healthcare-seeking behavior. The percentage of SARI with influenza virus detected is determined from provincial-level sentinel surveillance and applied to the adjusted provincial rates of hospitalized SARI. Healthcare-seeking data from healthcare utilization surveys is used to estimate non-hospitalized influenza-associated SARI. Rates of hospitalized and non-hospitalized influenza-associated SARI are applied to census data to calculate the national number of cases. The method was field-tested in Kenya, and validated in Guatemala, using data from August 2009–July 2011. In Kenya (2009 population 38.6 million persons), the annual number of hospitalized influenza-associated SARI cases ranged from 17,129–27,659 for children <5 years old (2.9–4.7 per 1,000 persons) and 6,882–7,836 for persons ≥5 years old (0.21–0.24 per 1,000 persons), depending on year and base rate used. In Guatemala (2011 population 14.7 million persons), the annual number of hospitalized cases of influenza-associated pneumonia ranged from 1,065–2,259 (0.5–1.0 per 1,000 persons) among children <5 years old and 779–2,252 cases (0.1–0.2 per 1,000 persons) for persons ≥5 years old, depending on year and base rate used. In both countries, the number of non-hospitalized influenza-associated cases was several-fold higher than the hospitalized cases. CONCLUSIONS: Influenza virus was associated with a substantial amount of severe disease in Kenya and Guatemala. This method can be performed in most low and lower-middle income countries.",2013 Feb 27,"['Fuller, James A.', 'Summers, Aimee', 'Katz, Mark A.', 'Lindblade, Kim A.', 'Njuguna, Henry', 'Arvelo, Wences', 'Khagayi, Sammy', 'Emukule, Gideon', 'Linares-Perez, Nivaldo', 'McCracken, John', 'Nokes, D. James', 'Ngama, Mwanajuma', 'Kazungu, Sidi', 'Mott, Joshua A.', 'Olsen, Sonja J.', 'Widdowson, Marc-Alain', 'Feikin, Daniel R.']",PLoS One,,,True
63cfec0de40f78765303a3fd6f853c672a193320,PMC,Humoral immune response to HTLV-1 basic leucine zipper factor (HBZ) in HTLV-1-infected individuals,http://dx.doi.org/10.1186/1742-4690-10-19,PMC3584941,23405908,CC BY,"BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1) infection can lead to development of adult T cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a subset of infected subjects. HTLV-1 basic leucine zipper factor (HBZ) gene has a critical role in HTLV-1 infectivity and the development of ATL and HAM/TSP. However, little is known about the immune response against HBZ in HTLV-1-infected individuals. In this study, we examined antibody responses against HBZ in serum/plasma samples from 436 subjects including HTLV-1 seronegative donors, asymptomatic carriers (AC), ATL, and HAM/TSP patients using the luciferase immunoprecipitation system. RESULTS: Immunoreactivity against HBZ was detected in subsets of all HTLV-1-infected individuals but the test did not discriminate between AC, ATL and HAM/TSP. However, the frequency of detection of HBZ-specific antibodies in the serum of ATL patients with the chronic subtype was higher than in ATL patients with the lymphomatous subtype. Antibody responses against HBZ were also detected in cerebrospinal fluid of HAM/TSP patients with anti-HBZ in serum. Antibody responses against HBZ did not correlate with proviral load and HBZ mRNA expression in HAM/TSP patients, but the presence of an HBZ-specific response was associated with reduced CD4(+) T cell activation in HAM/TSP patients. Moreover, HBZ-specific antibody inhibited lymphoproliferation in the PBMC of HAM/TSP patients. CONCLUSIONS: This is the first report demonstrating humoral immune response against HBZ associated with HTLV-I infection. Thus, a humoral immune response against HBZ might play a role in HTLV-1 infection.",2013 Feb 13,"['Enose-Akahata, Yoshimi', 'Abrams, Anna', 'Massoud, Raya', 'Bialuk, Izabela', 'Johnson, Kory R', 'Green, Patrick L', 'Maloney, Elizabeth M', 'Jacobson, Steven']",Retrovirology,,,True
df4824b457c47934bafd828367bb0377132a903c,PMC,Modeling Host Genetic Regulation of Influenza Pathogenesis in the Collaborative Cross,http://dx.doi.org/10.1371/journal.ppat.1003196,PMC3585141,23468633,CC BY,"Genetic variation contributes to host responses and outcomes following infection by influenza A virus or other viral infections. Yet narrow windows of disease symptoms and confounding environmental factors have made it difficult to identify polymorphic genes that contribute to differential disease outcomes in human populations. Therefore, to control for these confounding environmental variables in a system that models the levels of genetic diversity found in outbred populations such as humans, we used incipient lines of the highly genetically diverse Collaborative Cross (CC) recombinant inbred (RI) panel (the pre-CC population) to study how genetic variation impacts influenza associated disease across a genetically diverse population. A wide range of variation in influenza disease related phenotypes including virus replication, virus-induced inflammation, and weight loss was observed. Many of the disease associated phenotypes were correlated, with viral replication and virus-induced inflammation being predictors of virus-induced weight loss. Despite these correlations, pre-CC mice with unique and novel disease phenotype combinations were observed. We also identified sets of transcripts (modules) that were correlated with aspects of disease. In order to identify how host genetic polymorphisms contribute to the observed variation in disease, we conducted quantitative trait loci (QTL) mapping. We identified several QTL contributing to specific aspects of the host response including virus-induced weight loss, titer, pulmonary edema, neutrophil recruitment to the airways, and transcriptional expression. Existing whole-genome sequence data was applied to identify high priority candidate genes within QTL regions. A key host response QTL was located at the site of the known anti-influenza Mx1 gene. We sequenced the coding regions of Mx1 in the eight CC founder strains, and identified a novel Mx1 allele that showed reduced ability to inhibit viral replication, while maintaining protection from weight loss.",2013 Feb 28,"['Ferris, Martin T.', 'Aylor, David L.', 'Bottomly, Daniel', 'Whitmore, Alan C.', 'Aicher, Lauri D.', 'Bell, Timothy A.', 'Bradel-Tretheway, Birgit', 'Bryan, Janine T.', 'Buus, Ryan J.', 'Gralinski, Lisa E.', 'Haagmans, Bart L.', 'McMillan, Leonard', 'Miller, Darla R.', 'Rosenzweig, Elizabeth', 'Valdar, William', 'Wang, Jeremy', 'Churchill, Gary A.', 'Threadgill, David W.', 'McWeeney, Shannon K.', 'Katze, Michael G.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.']",PLoS Pathog,,,True
be464c3787cad446a8be522f9ed4793c16c81b49,PMC,Direct Observation of Membrane Insertion by Enveloped Virus Matrix Proteins by Phosphate Displacement,http://dx.doi.org/10.1371/journal.pone.0057916,PMC3585246,23469104,CC BY,"Enveloped virus release is driven by poorly understood proteins that are functional analogs of the coat protein assemblies that mediate intracellular vesicle trafficking. We used differential electron density mapping to detect membrane integration by membrane-bending proteins from five virus families. This demonstrates that virus matrix proteins replace an unexpectedly large portion of the lipid content of the inner membrane face, a generalized feature likely to play a role in reshaping cellular membranes.",2013 Feb 28,"['Neuman, Benjamin W.', 'Kiss, Gabriella', 'Al-Mulla, Hawaa M. N.', 'Dokland, Terje', 'Buchmeier, Michael J.', 'Weikl, Thomas', 'Schley, David']",PLoS One,,,True
20656a048091de934d0fb432f8d070304a1664dd,PMC,Native Tertiary Structure and Nucleoside Modifications Suppress tRNA’s Intrinsic Ability to Activate the Innate Immune Sensor PKR,http://dx.doi.org/10.1371/journal.pone.0057905,PMC3587421,23483938,CC BY,"Interferon inducible protein kinase PKR is an essential component of innate immunity. It is activated by long stretches of dsRNA and provides the first line of host defense against pathogens by inhibiting translation initiation in the infected cell. Many cellular and viral transcripts contain nucleoside modifications and/or tertiary structure that could affect PKR activation. We have previously demonstrated that a 5′-end triphosphate–a signature of certain viral and bacterial transcripts–confers the ability of relatively unstructured model RNA transcripts to activate PKR to inhibit translation, and that this activation is abrogated by certain modifications present in cellular RNAs. In order to understand the biological implications of native RNA tertiary structure and nucleoside modifications on PKR activation, we study here the heavily modified cellular tRNAs and the unmodified or the lightly modified mitochondrial tRNAs (mt-tRNA). We find that both a T7 transcript of yeast tRNA(Phe) and natively extracted total bovine liver mt-tRNA activate PKR in vitro, whereas native E. coli, bovine liver, yeast, and wheat tRNA(Phe) do not, nor do a variety of base- or sugar-modified T7 transcripts. These results are further supported by activation of PKR by a natively folded T7 transcript of tRNA(Phe) in vivo supporting the importance of tRNA modification in suppressing PKR activation in cells. We also examine PKR activation by a T7 transcript of the A14G pathogenic mutant of mt-tRNA(Leu), which is known to dimerize, and find that the misfolded dimeric form activates PKR in vitro while the monomeric form does not. Overall, the in vitro and in vivo findings herein indicate that tRNAs have an intrinsic ability to activate PKR and that nucleoside modifications and native RNA tertiary folding may function, at least in part, to suppress such activation, thus serving to distinguish self and non-self tRNA in innate immunity.",2013 Mar 4,"['Nallagatla, Subba Rao', 'Jones, Christie N.', 'Ghosh, Saikat Kumar B.', 'Sharma, Suresh D.', 'Cameron, Craig E.', 'Spremulli, Linda L.', 'Bevilacqua, Philip C.']",PLoS One,,,True
e2bfc8942cb7075af5dea8abbb281e0a7ec146a8,PMC,Native Tertiary Structure and Nucleoside Modifications Suppress tRNA’s Intrinsic Ability to Activate the Innate Immune Sensor PKR,http://dx.doi.org/10.1371/journal.pone.0057905,PMC3587421,23483938,CC BY,"Interferon inducible protein kinase PKR is an essential component of innate immunity. It is activated by long stretches of dsRNA and provides the first line of host defense against pathogens by inhibiting translation initiation in the infected cell. Many cellular and viral transcripts contain nucleoside modifications and/or tertiary structure that could affect PKR activation. We have previously demonstrated that a 5′-end triphosphate–a signature of certain viral and bacterial transcripts–confers the ability of relatively unstructured model RNA transcripts to activate PKR to inhibit translation, and that this activation is abrogated by certain modifications present in cellular RNAs. In order to understand the biological implications of native RNA tertiary structure and nucleoside modifications on PKR activation, we study here the heavily modified cellular tRNAs and the unmodified or the lightly modified mitochondrial tRNAs (mt-tRNA). We find that both a T7 transcript of yeast tRNA(Phe) and natively extracted total bovine liver mt-tRNA activate PKR in vitro, whereas native E. coli, bovine liver, yeast, and wheat tRNA(Phe) do not, nor do a variety of base- or sugar-modified T7 transcripts. These results are further supported by activation of PKR by a natively folded T7 transcript of tRNA(Phe) in vivo supporting the importance of tRNA modification in suppressing PKR activation in cells. We also examine PKR activation by a T7 transcript of the A14G pathogenic mutant of mt-tRNA(Leu), which is known to dimerize, and find that the misfolded dimeric form activates PKR in vitro while the monomeric form does not. Overall, the in vitro and in vivo findings herein indicate that tRNAs have an intrinsic ability to activate PKR and that nucleoside modifications and native RNA tertiary folding may function, at least in part, to suppress such activation, thus serving to distinguish self and non-self tRNA in innate immunity.",2013 Mar 4,"['Nallagatla, Subba Rao', 'Jones, Christie N.', 'Ghosh, Saikat Kumar B.', 'Sharma, Suresh D.', 'Cameron, Craig E.', 'Spremulli, Linda L.', 'Bevilacqua, Philip C.']",PLoS One,,,False
15f3da54587d39ca8a3c8eabffb84fc463266ab0,PMC,Complete Genome Sequence of a Variant Porcine Epidemic Diarrhea Virus Strain Isolated in Central China,http://dx.doi.org/10.1128/genomeA.00243-12,PMC3587950,23469356,CC BY,"We report here the complete genome sequence of the porcine epidemic diarrhea virus strain CH/ZMDZY/11 isolated from central China. Our data, together with sequence data of porcine epidemic diarrhea virus (PEDV) isolates from other parts in China, will help to understand better the epidemiology and genetic diversity of PEDV field isolates in China.",2013 Feb 21,"['Wang, Xiao-Meng', 'Niu, Bei-Bei', 'Yan, He', 'Gao, Dong-Sheng', 'Huo, Jin-Yao', 'Chen, Lu', 'Chang, Hong-Tao', 'Wang, Chuan-qing', 'Zhao, Jun']",Genome Announc,,,True
757d0a46fdff943b64a2e8f7c6ac2132da44c6d5,PMC,"Ethyl 4-(5-bromo-1H-indol-3-yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate",http://dx.doi.org/10.1107/S1600536812046909,PMC3588994,23476230,CC BY,"The title compound, C(23)H(25)BrN(2)O(3), crystallizes with two independent molecules in the asymmetric unit (Z′ = 2) which differ in the twist of the 5-bromo-1H-indole ring with respect to the plane of the 4-methyl-1,4,5,6,7,8-hexahydroquinoline ring [dihedral angles of 78.55 (9) and 89.70 (8)° in molecules A and B, respectively]. The indole ring is planar in both molecules [maximum deviations = 0.021 (3) and −0.020 (3) Å for the N atom] while the cyclohexene ring has adopts a sofa conformation. In the crystal, molecules are linked by pairs of N—H⋯O hydrogen bonds, forming dimers with R (1) (2)(6) ring motifs. These dimers are connected by N—H⋯O hydrogen bonds, generating chains along [110]. A C—H⋯O contact occurs between the independent molecules.",2012 Nov 24,"['Gündüz, Miyase Gözde', 'Butcher, Ray J.', 'Öztürk Yildirim, Sema', 'El-Khouly, Ahmed', 'Şafak, Cihat', 'Şimşek, Rahime']",Acta Crystallogr Sect E Struct Rep Online,,,True
b406fb73bb91dd7aed57b8187b69a5db7e83bd85,PMC,Using Routine Surveillance Data to Estimate the Epidemic Potential of Emerging Zoonoses: Application to the Emergence of US Swine Origin Influenza A H3N2v Virus,http://dx.doi.org/10.1371/journal.pmed.1001399,PMC3589342,23472057,CC BY,"BACKGROUND: Prior to emergence in human populations, zoonoses such as SARS cause occasional infections in human populations exposed to reservoir species. The risk of widespread epidemics in humans can be assessed by monitoring the reproduction number R (average number of persons infected by a human case). However, until now, estimating R required detailed outbreak investigations of human clusters, for which resources and expertise are not always available. Additionally, existing methods do not correct for important selection and under-ascertainment biases. Here, we present simple estimation methods that overcome many of these limitations. METHODS AND FINDINGS: Our approach is based on a parsimonious mathematical model of disease transmission and only requires data collected through routine surveillance and standard case investigations. We apply it to assess the transmissibility of swine-origin influenza A H3N2v-M virus in the US, Nipah virus in Malaysia and Bangladesh, and also present a non-zoonotic example (cholera in the Dominican Republic). Estimation is based on two simple summary statistics, the proportion infected by the natural reservoir among detected cases (G) and among the subset of the first detected cases in each cluster (F). If detection of a case does not affect detection of other cases from the same cluster, we find that R can be estimated by 1−G; otherwise R can be estimated by 1−F when the case detection rate is low. In more general cases, bounds on R can still be derived. CONCLUSIONS: We have developed a simple approach with limited data requirements that enables robust assessment of the risks posed by emerging zoonoses. We illustrate this by deriving transmissibility estimates for the H3N2v-M virus, an important step in evaluating the possible pandemic threat posed by this virus. Please see later in the article for the Editors' Summary",2013 Mar 5,"['Cauchemez, Simon', 'Epperson, Scott', 'Biggerstaff, Matthew', 'Swerdlow, David', 'Finelli, Lyn', 'Ferguson, Neil M.']",PLoS Med,,,True
2cf982b22e1f2deebca01ece2c70b0e4828ebc21,PMC,Clonal Expansions of CD8(+) T Cells with IL-10 Secreting Capacity Occur during Chronic Mycobacterium tuberculosis Infection,http://dx.doi.org/10.1371/journal.pone.0058612,PMC3589362,23472214,CC BY,"The exact role of CD8(+) T cells during Mycobacterium tuberculosis (Mtb) infection has been heavily debated, yet it is generally accepted that CD8(+) T cells contribute to protection against Mtb. In this study, however, we show that the Mtb-susceptible CBA/J mouse strain accumulates large numbers of CD8(+) T cells in the lung as infection progresses, and that these cells display a dysfunctional and immunosuppressive phenotype (PD-1(+), Tim-3(+), CD122(+)). CD8(+) T cell expansions from the lungs of Mtb-infected CBA/J mice were also capable of secreting the immunosuppressive cytokine interleukin-10 (IL-10), although in vivo CD8(+) T cell depletion did not significantly alter Mtb burden. Further analysis revealed that pulmonary CD8(+) T cells from Mtb-infected CBA/J mice were clonally expanded, preferentially expressing T cell receptor (TcR) Vβ chain 8 (8.2, 8.3) or Vβ 14. Although Vβ8(+) CD8(+) T cells were responsible for the majority of IL-10 production, in vivo depletion of Vβ8(+) did not significantly change the outcome of Mtb infection, which we hypothesize was a consequence of their dual IL-10/IFN-γ secreting profiles. Our data demonstrate that IL-10-secreting CD8(+) T cells can arise during chronic Mtb infection, although the significance of this T cell population in tuberculosis pathogenesis remains unclear.",2013 Mar 5,"['Cyktor, Joshua C.', 'Carruthers, Bridget', 'Beamer, Gillian L.', 'Turner, Joanne']",PLoS One,,,True
7b9bd316f8dddb71be863728f6dba041b0d6d402,PMC,Beet yellows virus replicase and replicative compartments: parallels with other RNA viruses,http://dx.doi.org/10.3389/fmicb.2013.00038,PMC3589766,23508802,CC BY,"In eukaryotic virus systems, infection leads to induction of membranous compartments in which replication occurs. Virus-encoded subunits of the replication complex mediate its interaction with membranes. As replication platforms, RNA viruses use the cytoplasmic surfaces of different membrane compartments, e.g., endoplasmic reticulum (ER), Golgi, endo/lysosomes, mitochondria, chloroplasts, and peroxisomes. Closterovirus infections are accompanied by formation of multivesicular complexes from cell membranes of ER or mitochondrial origin. So far the mechanisms for vesicles formation have been obscure. In the replication-associated 1a polyprotein of Beet yellows virus (BYV) and other closteroviruses, the region between the methyltransferase and helicase domains (1a central region (CR), 1a CR) is marginally conserved. Computer-assisted analysis predicts several putative membrane-binding domains in the BYV 1a CR. Transient expression of a hydrophobic segment (referred to here as CR-2) of the BYV 1a in Nicotiana benthamiana led to reorganization of the ER and formation of ~1-μm mobile globules. We propose that the CR-2 may be involved in the formation of multivesicular complexes in BYV-infected cells. This provides analogy with membrane-associated proteins mediating the build-up of “virus factories” in cells infected with diverse positive-strand RNA viruses (alpha-like viruses, picorna-like viruses, flaviviruses, and nidoviruses) and negative-strand RNA viruses (bunyaviruses).",2013 Mar 6,"['Gushchin, Vladimir A.', 'Solovyev, Andrey G.', 'Erokhina, Tatyana N.', 'Morozov, Sergey Y.', 'Agranovsky, Alexey A.']",Front Microbiol,,,True
7a31ec5e53aa0adf7ae3f8caa2b02b72d2123f37,PMC,Genomics and computational science for virus research,http://dx.doi.org/10.3389/fmicb.2013.00042,PMC3590459,23472060,CC BY,,2013 Mar 7,"['Sato, Hironori', 'Yokoyama, Masaru', 'Toh, Hiroyuki']",Front Microbiol,,,True
baa22aecb85ba7258afa2c07891ea8f08acdefa7,PMC,Exploratory Analysis of Methods for Automated Classification of Laboratory Test Orders into Syndromic Groups in Veterinary Medicine,http://dx.doi.org/10.1371/journal.pone.0057334,PMC3591392,23505427,CC BY,"BACKGROUND: Recent focus on earlier detection of pathogen introduction in human and animal populations has led to the development of surveillance systems based on automated monitoring of health data. Real- or near real-time monitoring of pre-diagnostic data requires automated classification of records into syndromes–syndromic surveillance–using algorithms that incorporate medical knowledge in a reliable and efficient way, while remaining comprehensible to end users. METHODS: This paper describes the application of two of machine learning (Naïve Bayes and Decision Trees) and rule-based methods to extract syndromic information from laboratory test requests submitted to a veterinary diagnostic laboratory. RESULTS: High performance (F(1)-macro = 0.9995) was achieved through the use of a rule-based syndrome classifier, based on rule induction followed by manual modification during the construction phase, which also resulted in clear interpretability of the resulting classification process. An unmodified rule induction algorithm achieved an F(1-micro) score of 0.979 though this fell to 0.677 when performance for individual classes was averaged in an unweighted manner (F(1-macro)), due to the fact that the algorithm failed to learn 3 of the 16 classes from the training set. Decision Trees showed equal interpretability to the rule-based approaches, but achieved an F(1-micro) score of 0.923 (falling to 0.311 when classes are given equal weight). A Naïve Bayes classifier learned all classes and achieved high performance (F(1-micro) = 0.994 and F(1-macro) = .955), however the classification process is not transparent to the domain experts. CONCLUSION: The use of a manually customised rule set allowed for the development of a system for classification of laboratory tests into syndromic groups with very high performance, and high interpretability by the domain experts. Further research is required to develop internal validation rules in order to establish automated methods to update model rules without user input.",2013 Mar 7,"['Dórea, Fernanda C.', 'Muckle, C. Anne', 'Kelton, David', 'McClure, JT.', 'McEwen, Beverly J.', 'McNab, W. Bruce', 'Sanchez, Javier', 'Revie, Crawford W.']",PLoS One,,,True
ecbee46a2f987fb95c2b1a5b0e4d789ea654a19e,PMC,Max Bergmann lecture Protein epitope mimetics in the age of structural vaccinology‡,http://dx.doi.org/10.1002/psc.2482,PMC3592999,23349031,CC BY,"This review highlights the growing importance of protein epitope mimetics in the discovery of new biologically active molecules and their potential applications in drug and vaccine research. The focus is on folded β-hairpin mimetics, which are designed to mimic β-hairpin motifs in biologically important peptides and proteins. An ever-growing number of protein crystal structures reveal how β-hairpin motifs often play key roles in protein–protein and protein–nucleic acid interactions. This review illustrates how using protein structures as a starting point for small-molecule mimetic design can provide novel ligands as protein–protein interaction inhibitors, as protease inhibitors, and as ligands for chemokine receptors and folded RNA targets, as well as novel antibiotics to combat the growing health threat posed by the emergence of antibiotic-resistant bacteria. The β-hairpin antibiotics are shown to target a β-barrel outer membrane protein (LptD) in Pseudomonas sp., which is essential for the biogenesis of the outer cell membrane. Another exciting prospect is that protein epitope mimetics will be of increasing importance in synthetic vaccine design, in the emerging field of structural vaccinology. Crystal structures of protective antibodies bound to their pathogen-derived epitopes provide an ideal starting point for the design of synthetic epitope mimetics. The mimetics can be delivered to the immune system in a highly immunogenic format on the surface of synthetic virus-like particles. The scientific challenges in molecular design remain great, but the potential significance of success in this area is even greater. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.",2013 Mar 24,"Robinson, John A",J Pept Sci,,,True
f60eb9280104d1ff7ca8ade5a7ccdeca43afce2f,PMC,Novel Human Gammapapillomavirus Species in a Nasal Swab,http://dx.doi.org/10.1128/genomeA.00022-13,PMC3593334,23516180,CC BY,"A divergent human gammapapillomavirus (γ-HPV) genome in a nasal swab from an elderly Finnish patient with respiratory symptoms was genetically characterized. The L1 gene of HPV-Fin864 shared <70% nucleotide identity to other reported γ-HPV genomes, provisionally qualifying it as a new species in the Gammapapillomavirus genus.",2013 Mar 7,"['Phan, Tung Gia', 'Vo, Nguyen P.', 'Aronen, Matti', 'Jartti, Laura', 'Jartti, Tuomas', 'Delwart, Eric']",Genome Announc,,,True
532e417a66dbe4822a3f8f9b496c105ccc7dd412,PMC,"Vaccination to Conserved Influenza Antigens in Mice Using a Novel Simian Adenovirus Vector, PanAd3, Derived from the Bonobo Pan paniscus",http://dx.doi.org/10.1371/journal.pone.0055435,PMC3594242,23536756,CC0,"Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus) has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP) and matrix 1 (M1). We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines.",2013 Mar 11,"['Vitelli, Alessandra', 'Quirion, Mary R.', 'Lo, Chia-Yun', 'Misplon, Julia A.', 'Grabowska, Agnieszka K.', 'Pierantoni, Angiolo', 'Ammendola, Virginia', 'Price, Graeme E.', 'Soboleski, Mark R.', 'Cortese, Riccardo', 'Colloca, Stefano', 'Nicosia, Alfredo', 'Epstein, Suzanne L.']",PLoS One,,,True
54ca96205e785170fff9f439860d4f4fa4d95782,PMC,The Role of Cysteine Proteinases and their Inhibitors in the Host-Pathogen Cross Talk,http://dx.doi.org/10.2174/138920312804871102,PMC3594739,23305363,CC BY,"Proteinases and their inhibitors play essential functional roles in basic biological processes in both hosts and pathogens. Endo/lysosomal cathepsins participate in immune response in pathogen recognition and elimination. They are essential for both antigen processing and presentation (host adaptive immune response) and activation of endosomal Toll like receptors (innate immune response). Pathogens can produce proteases and also natural inhibitors to subvert the host immune response. Several pathogens are sensed through the intracellular pathogen recognition receptors, but only some of them use the host proteolytic system to escape into the cytosol. In this review, I provide an update on the most recent developments regarding the role of proteinases and their inhibitors in the initiation and regulation of immune responses.",2012 Dec,"Kopitar-Jerala, Nataša",Curr Protein Pept Sci,,,True
8437870dfb10809764da7204fd758ff3e9ee85db,PMC,Dangerous liaisons: molecular basis for a syndemic relationship between Kaposi’s sarcoma and P. falciparum malaria,http://dx.doi.org/10.3389/fmicb.2013.00035,PMC3594938,23487416,CC BY,"The most severe manifestations of malaria (caused by Plasmodium falciparum) occur as a direct result of parasitemia following invasion of erythrocytes by post-liver blood-stage merozoites, and during subsequent cyto-adherence of infected erythrocytes to the vascular endothelium. However, the disproportionate epidemiologic clustering of severe malaria with aggressive forms of endemic diseases such as Kaposi’s sarcoma (KS), a neoplasm that is etiologically linked to infection with KS-associated herpesvirus (KSHV), underscores the significance of previously unexplored co-pathogenetic interactions that have the potential to modify the overall disease burden in co-infected individuals. Based on recent studies of the mechanisms that P. falciparum and KSHV have evolved to interact with their mutual human host, several new perspectives are emerging that highlight a surprising convergence of biological themes potentially underlying their associated co-morbidities. Against this background, ongoing studies are rapidly constructing a fascinating new paradigm in which the major host receptors that control parasite invasion (Basigin/CD147) and cyto-adherence (CD36) are, surprisingly, also important targets for exploitation by KSHV. In this article, we consider the major pathobiological implications of the co-option of Basigin/CD147 and CD36 signaling pathways by both P. falciparum and KSHV, not only as essential host factors for parasite persistence but also as important mediators of the pro-angiogenic phenotype within the virus-infected endothelial microenvironment. Consequently, the triangulation of interactions between P. falciparum, KSHV, and their mutual human host articulates a syndemic relationship that points to a conceptual framework for prevalence of aggressive forms of KS in malaria-endemic areas, with implications for the possibility of dual-use therapies against these debilitating infections in resource-limited parts of the world.",2013 Mar 12,"['Conant, Katelyn L.', 'Kaleeba, Johnan A. R.']",Front Microbiol,,,True
b75f738ed440a2a6bd3f129238c0e661024577cb,PMC,Harnessing DNA Synthesis to Develop Rapid Responses to Emerging and Pandemic Pathogens,http://dx.doi.org/10.4061/2011/765763,PMC3595711,23533775,CC BY,"Given the interconnected nature of our world today, emerging pathogens and pandemic outbreaks are an ever-growing threat to the health and economic stability of the global community. This is evident by the recent 2009 Influenza A (H1N1) pandemic, the SARS outbreak, as well as the ever-present threat of global bioterrorism. Fortunately, the biomedical community has been able to rapidly generate sequence data so these pathogens can be readily identified. To date, however, the utilization of this sequence data to rapidly produce relevant experimental results or actionable treatments is lagging in spite of obtained sequence data. Thus, a pathogenic threat that has emerged and/or developed into a pandemic can be rapidly identified; however, translating this identification into a targeted therapeutic or treatment that is rapidly available has not yet materialized. This commentary suggests that the growing technology of DNA synthesis should be fully implemented as a means to rapidly generate in vivo data and possibly actionable therapeutics soon after sequence data becomes available.",2011 Mar 16,"['Runco, Lisa M.', 'Coleman, J. Robert']",J Pathog,,,True
df783d511b145a10e7f609a87392eb50799d2b2b,PMC,"NOA36 Protein Contains a Highly Conserved Nucleolar Localization Signal Capable of Directing Functional Proteins to the Nucleolus, in Mammalian Cells",http://dx.doi.org/10.1371/journal.pone.0059065,PMC3596294,23516598,CC BY,"NOA36/ZNF330 is an evolutionarily well-preserved protein present in the nucleolus and mitochondria of mammalian cells. We have previously reported that the pro-apoptotic activity of this protein is mediated by a characteristic cysteine-rich domain. We now demonstrate that the nucleolar localization of NOA36 is due to a highly-conserved nucleolar localization signal (NoLS) present in residues 1–33. This NoLS is a sequence containing three clusters of two or three basic amino acids. We fused the amino terminal of NOA36 to eGFP in order to characterize this putative NoLS. We show that a cluster of three lysine residues at positions 3 to 5 within this sequence is critical for the nucleolar localization. We also demonstrate that the sequence as found in human is capable of directing eGFP to the nucleolus in several mammal, fish and insect cells. Moreover, this NoLS is capable of specifically directing the cytosolic yeast enzyme polyphosphatase to the target of the nucleolus of HeLa cells, wherein its enzymatic activity was detected. This NoLS could therefore serve as a very useful tool as a nucleolar marker and for directing particular proteins to the nucleolus in distant animal species.",2013 Mar 13,"['de Melo, Ivan S.', 'Jimenez-Nuñez, Maria D.', 'Iglesias, Concepción', 'Campos-Caro, Antonio', 'Moreno-Sanchez, David', 'Ruiz, Felix A.', 'Bolívar, Jorge']",PLoS One,,,True
8df99ad6d9b0d27c66f51580651c7bf1707bf275,PMC,"NOA36 Protein Contains a Highly Conserved Nucleolar Localization Signal Capable of Directing Functional Proteins to the Nucleolus, in Mammalian Cells",http://dx.doi.org/10.1371/journal.pone.0059065,PMC3596294,23516598,CC BY,"NOA36/ZNF330 is an evolutionarily well-preserved protein present in the nucleolus and mitochondria of mammalian cells. We have previously reported that the pro-apoptotic activity of this protein is mediated by a characteristic cysteine-rich domain. We now demonstrate that the nucleolar localization of NOA36 is due to a highly-conserved nucleolar localization signal (NoLS) present in residues 1–33. This NoLS is a sequence containing three clusters of two or three basic amino acids. We fused the amino terminal of NOA36 to eGFP in order to characterize this putative NoLS. We show that a cluster of three lysine residues at positions 3 to 5 within this sequence is critical for the nucleolar localization. We also demonstrate that the sequence as found in human is capable of directing eGFP to the nucleolus in several mammal, fish and insect cells. Moreover, this NoLS is capable of specifically directing the cytosolic yeast enzyme polyphosphatase to the target of the nucleolus of HeLa cells, wherein its enzymatic activity was detected. This NoLS could therefore serve as a very useful tool as a nucleolar marker and for directing particular proteins to the nucleolus in distant animal species.",2013 Mar 13,"['de Melo, Ivan S.', 'Jimenez-Nuñez, Maria D.', 'Iglesias, Concepción', 'Campos-Caro, Antonio', 'Moreno-Sanchez, David', 'Ruiz, Felix A.', 'Bolívar, Jorge']",PLoS One,,,False
f9faf42edda00faefb4ea08c2c4234b027990579,PMC,Human herpesvirus 6A induces apoptosis of HSB-2 cells via a mitochondrion-related caspase pathway(),http://dx.doi.org/10.1016/S1674-8301(10)60059-0,PMC3596692,23554661,CC BY,"Apoptosis plays an important role in the pathogenesis of viral infections. In this study, we investigated the cell death processes during productive HHV-6A infection and the underlying mechanisms. Annexin V-PI staining and electron microscopy indicated that HHV-6A is a strong inducer of apoptosis. HHV-6A infection decreased mitochondrial transmembrane potential and led to morphological changes of mitochondria. The cell death was associated with activation of caspase-3 and cleavage of DNA repair enzyme poly (ADP-ribose) polymerase, which is known to be an important substrate for activated caspase-3. Caspase-9 was activated significantly in HHV-6A-infected cells, whereas caspase-8 was not activated obviously. Moreover, HHV-6A infection upregulated Bax and downregulated Bcl-2. This is the first demonstration of mitochondrion-mediated, caspase-dependent apoptosis in HHV-6A-infected cells.",2010 Nov,"['Li, Lingyun', 'Chi, Jing', 'Zhou, Feng', 'Guo, Dandan', 'Wang, Fang', 'Liu, Genyan', 'Zhang, Chun', 'Yao, Kun']",J Biomed Res,,,True
e22140a30bea1676104edacd5240407c1f0d36a5,PMC,Comparative domain modeling of human EGF-like module EMR2 and study of interaction of the fourth domain of EGF with chondroitin 4-sulphate(),http://dx.doi.org/10.1016/S1674-8301(11)60013-4,PMC3596701,23554678,CC BY,"EMR2 is an EGF-like module containing mucin-like hormone receptor-2 precursor, a G-protein coupled receptor (G-PCR). Mutation in EMR2 causes complicated disorders like polycystic kidney disease (PKD). The structure of EMR2 shows that the fifth domain is comprised of EGF-TM7 helices. Functional assignment of EMR2 by support vector machine (SVM) revealed that along with transporter activity, several novel functions are predicted. A twenty amino acid sequence “MGGRVFLVFLAFCVWLTLPG” acts as the signal peptide responsible for posttranslational transport. Eight amino acids are involved in N-glycosylation sites and two cleavage sites are Leu517 and Ser518 in EMR2. The residue Arg241 is responsible for interaction with glycosaminoglycan and chondroitin sulfate. On the basis of structure, function and ligand binding sites, competitive EMR2 inhibitors designed may decrease the rate of human diseases like Usher's syndrome, bilateral frontoparietal polymicrogyria and PKD.",2011 Mar,"['Rani, Mukta', 'Dikhit, Manas R.', 'Sahoo, Ganesh C', 'Das, Pradeep']",J Biomed Res,,,True
2e6e30e494cf5e2216a4ac5cd2878a17ce8fc4b7,PMC,First introduction of pandemic influenza A/H1N1 and detection of respiratory viruses in pediatric patients in Central African Republic,http://dx.doi.org/10.1186/1743-422X-10-49,PMC3598402,23391188,CC BY,"BACKGROUND: Acute viral respiratory illnesses in children in sub-Saharan Africa have received relatively little attention, although they are much more frequent causes of morbidity and mortality than in developed countries. Active surveillance is essential to identify the causative agents and to improve clinical management, especially in the context of possible circulation of pandemic viruses. FINDINGS: A prospective study was conducted in the Central African Republic (CAR) between January and December 2010 among infants and children aged 0–15 years attending sentinel sites for influenza-like illness or acute respiratory illness. Nasopharyngeal swabs were collected, and one-step real-time and multiplex reverse transcription-polymerase chain reaction were used to detect respiratory viruses. Respiratory viruses were detected in 49 of the 329 (14.9%) nasopharyngeal samples: 29 (8.8%) contained influenza viruses (5 (1.5%) had pandemic influenza A/H1N1 virus and 24 (7.3%) had influenza B viruses), 11 (3.3%) contained parainfluenza viruses types 1 and 3 and 9 (2.7%) contained human respiratory syncytial virus. Most cases were detected during the rainy season in the CAR. Analysis of the amplicon sequences confirmed the identity of each detected virus. CONCLUSIONS: The influenza surveillance system in the CAR has provided valuable data on the seasonality of influenza and the circulation of other respiratory viruses. Our network could therefore play a valuable role in the prevention and control of influenza epidemics in the CAR.",2013 Feb 8,"['Nakouné, Emmanuel', 'Tricou, Vianney', 'Manirakiza, Alexandre', 'Komoyo, Francis', 'Selekon, Benjamin', 'Gody, Jean Chrysostome', 'Victoir, Kathleen', 'Buchy, Philippe', 'Kazanji, Mirdad']",Virol J,,,True
b6c747316db8f591a729c4ed060a6df0e3a18fc8,PMC,Inhaled corticosteroid use is associated with increased circulating T regulatory cells in children with asthma,http://dx.doi.org/10.1186/1476-7961-11-1,PMC3598778,23347774,CC BY,"BACKGROUND: T regulatory (Treg) cells are important in balancing immune responses and dysregulation of Treg cells has been implicated in the pathogenesis of multiple disease states including asthma. In this study, our primary aim was to determine Treg cell frequency in the peripheral blood of children with and without asthma. The secondary aim was to explore the association between Treg cell frequency with allergen sensitization, disease severity and medication use. METHODS: Peripheral blood mononuclear cells from healthy control subjects (N = 93) and asthmatic children of varying disease severity (N = 66) were characterized by multi-parameter flow cytometry. RESULTS: Our findings demonstrate that children with asthma had a significantly increased frequency of Treg cells compared to children without asthma. Using a multivariate model, increased Treg cell frequency in children with asthma was most directly associated with inhaled corticosteroid use, and not asthma severity, allergic sensitization, or atopic status of the asthma. CONCLUSION: We conclude that low dose, local airway administration of corticosteroids is sufficient to impact the frequency of Treg cells in the peripheral blood. These data highlight the importance of considering medication exposure when studying Treg cells and suggest inhaled corticosteroid use in asthmatics may improve disease control through increased Treg cell frequency.",2013 Jan 25,"['Singh, Anne Marie', 'Dahlberg, Paul', 'Burmeister, Kristjan', 'Evans, Michael D', 'Gangnon, Ronald', 'Roberg, Kathy A', 'Tisler, Christopher', 'DaSilva, Douglas', 'Pappas, Tressa', 'Salazar, Lisa', 'Lemanske, Robert F', 'Gern, James E', 'Seroogy, Christine M']",Clin Mol Allergy,,,True
1b8bd44173742cd254617aabc5fdf20fb98f4072,PMC,Severe lower respiratory tract infection in infants and toddlers from a non-affluent population: viral etiology and co-detection as risk factors,http://dx.doi.org/10.1186/1471-2334-13-41,PMC3598993,23351117,CC BY,"BACKGROUND: Lower respiratory tract infection (LRTI) is a major cause of pediatric morbidity and mortality, especially among non-affluent communities. In this study we determine the impact of respiratory viruses and how viral co-detections/infections can affect clinical LRTI severity in children in a hospital setting. METHODS: Patients younger than 3 years of age admitted to a tertiary hospital in Brazil during the months of high prevalence of respiratory viruses had samples collected from nasopharyngeal aspiration. These samples were tested for 13 different respiratory viruses through real-time PCR (rt-PCR). Patients were followed during hospitalization, and clinical data and population characteristics were collected during that period and at discharge to evaluate severity markers, especially length of hospital stay and oxygen use. Univariate regression analyses identified potential risk factors and multivariate logistic regressions were used to determine the impact of specific viral detections as well as viral co-detections in relation to clinical outcomes. RESULTS: We analyzed 260 episodes of LRTI with a viral detection rate of 85% (n = 222). Co-detection was observed in 65% of all virus-positive episodes. The most prevalent virus was Respiratory Syncytial Virus (RSV) (54%), followed by Human Metapneumovirus (hMPV) (32%) and Human Rhinovirus (HRV) (21%). In the multivariate models, infants with co-detection of HRV + RSV stayed 4.5 extra days (p = 0.004), when compared to infants without the co-detection. The same trends were observed for the outcome of days of supplemental oxygen use. CONCLUSIONS: Although RSV remains as the main cause of LRTI in infants our study indicates an increase in the length of hospital stay and oxygen use in infants with HRV detected by RT-PCR compared to those without HRV. Moreover, one can speculate that when HRV is detected simultaneously with RSV there is an additive effect that may be reflected in more severe clinical outcome. Also, our study identified a significant number of children infected by recently identified viruses, such as hMPV and Human Bocavirus (HBov), and this is a novel finding for poor communities from developing countries.",2013 Jan 25,"['da Silva, Emerson Rodrigues', 'Pitrez, Márcio Condessa Paulo', 'Arruda, Eurico', 'Mattiello, Rita', 'Sarria, Edgar E', 'de Paula, Flávia Escremim', 'Proença-Modena, José Luis', 'Delcaro, Luana Sella', 'Cintra, Otávio', 'Jones, Marcus H', 'Ribeiro, José Dirceu', 'Stein, Renato T']",BMC Infect Dis,,,True
956d1b132a0bb6b7ebd9ca19e312ef0fd7ca7cb9,PMC,Reverse transcription loop-mediated isothermal amplification assay for rapid detection of Bovine Rotavirus,http://dx.doi.org/10.1186/1746-6148-8-133,PMC3599620,22894568,CC BY,"BACKGROUND: Bovine rotavirus (BRV) infection is common in young calves. This viral infection causes acute diarrhea leading to death. Rapid identification of infected calves is essential to control BRV successfully. Therefore development of simple, highly specific, and sensitive detection method for BRV is needed. RESULTS: A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed and optimized for rapid detection of BRV. Specific primer sets were designed to target the sequences of the VP6 gene of the neonatal calf diarrhea virus (NCDV) strain of BRV. The RT-LAMP assay was performed in a water bath for 60 minutes at 63°C, and the amplification products were visualized either directly or under ultraviolet light. This BRV specific RT-LAMP assay could detect 3.32 copies of subtype A BRV. No cross-reactions were detected with other bovine pathogens. The ability of RT-LAMP to detect bovine rotavirus was further evaluated with 88 bovine rectal swab samples. Twenty-nine of these samples were found to be positive for BRV using RT-LAMP. The BRV-specific-RT-LAMP results were also confirmed by real-time RT-PCR assay. CONCLUSIONS: The bovine rotavirus-specific RT-LAMP assay was highly sensitive and holds promise as a prompt and simple diagnostic method for the detection of group A bovine rotavirus infection in young calves.",2012 Aug 15,"['Xie, Zhixun', 'Fan, Qing', 'Liu, Jiabo', 'Pang, Yaoshan', 'Deng, Xianwen', 'Xie, Zhiqin', 'Liji, Xie', 'Khan, Mazhar I']",BMC Vet Res,,,True
652fdea5cc6137511f2de628166875707670b10b,PMC,Ultra-deep mutant spectrum profiling: improving sequencing accuracy using overlapping read pairs,http://dx.doi.org/10.1186/1471-2164-14-96,PMC3599684,23402258,CC BY,"BACKGOUND: High throughput sequencing is beginning to make a transformative impact in the area of viral evolution. Deep sequencing has the potential to reveal the mutant spectrum within a viral sample at high resolution, thus enabling the close examination of viral mutational dynamics both within- and between-hosts. The challenge however, is to accurately model the errors in the sequencing data and differentiate real viral mutations, particularly those that exist at low frequencies, from sequencing errors. RESULTS: We demonstrate that overlapping read pairs (ORP) -- generated by combining short fragment sequencing libraries and longer sequencing reads -- significantly reduce sequencing error rates and improve rare variant detection accuracy. Using this sequencing protocol and an error model optimized for variant detection, we are able to capture a large number of genetic mutations present within a viral population at ultra-low frequency levels (<0.05%). CONCLUSIONS: Our rare variant detection strategies have important implications beyond viral evolution and can be applied to any basic and clinical research area that requires the identification of rare mutations.",2013 Feb 12,"['Chen-Harris, Haiyin', 'Borucki, Monica K', 'Torres, Clinton', 'Slezak, Tom R', 'Allen, Jonathan E']",BMC Genomics,,,True
57c211a07941fdfee4da06fd1e364234ea30b7f9,PMC,Ultra-deep mutant spectrum profiling: improving sequencing accuracy using overlapping read pairs,http://dx.doi.org/10.1186/1471-2164-14-96,PMC3599684,23402258,CC BY,"BACKGOUND: High throughput sequencing is beginning to make a transformative impact in the area of viral evolution. Deep sequencing has the potential to reveal the mutant spectrum within a viral sample at high resolution, thus enabling the close examination of viral mutational dynamics both within- and between-hosts. The challenge however, is to accurately model the errors in the sequencing data and differentiate real viral mutations, particularly those that exist at low frequencies, from sequencing errors. RESULTS: We demonstrate that overlapping read pairs (ORP) -- generated by combining short fragment sequencing libraries and longer sequencing reads -- significantly reduce sequencing error rates and improve rare variant detection accuracy. Using this sequencing protocol and an error model optimized for variant detection, we are able to capture a large number of genetic mutations present within a viral population at ultra-low frequency levels (<0.05%). CONCLUSIONS: Our rare variant detection strategies have important implications beyond viral evolution and can be applied to any basic and clinical research area that requires the identification of rare mutations.",2013 Feb 12,"['Chen-Harris, Haiyin', 'Borucki, Monica K', 'Torres, Clinton', 'Slezak, Tom R', 'Allen, Jonathan E']",BMC Genomics,,,False
402334dfcf4430553c3f99a5bbe869a3882c1d97,PMC,Porcine CD8α(dim/-)NKp46(high) NK cells are in a highly activated state,http://dx.doi.org/10.1186/1297-9716-44-13,PMC3599810,23452562,CC BY,"Natural Killer (NK) cells play a crucial role in the early phase of immune responses against various pathogens. In swine so far only little information about this lymphocyte population exists. Phenotypical analyses with newly developed monoclonal antibodies (mAbs) against porcine NKp46 recently revealed that in blood NKp46(-) and NKp46(+) cells with NK phenotype exist with comparable cytotoxic properties. In spleen a third NKp46-defined population with NK phenotype was observed that was characterised by a low to negative CD8α and increased NKp46 expression. In the current study it is shown that this NKp46(high) phenotype was correlated with an increased expression of CD16 and CD27 compared to the CD8α(+)NKp46(-) and NKp46(+) NK-cell subsets in spleen and blood. Additionally NKp46(high) NK cells expressed elevated levels of the chemokine receptor CXCR3 on mRNA level. Functional analyses revealed that splenic NKp46(high) NK cells produced much higher levels of Interferon-γ and Tumor Necrosis Factor-α upon stimulation with cytokines or phorbol-12-myristate-13-acetate/Ionomycin compared to the other two subsets. Furthermore, cross-linking of NKp46 by NKp46-specific mAbs led to a superior CD107a expression in the NKp46(high) NK cells, thus indicating a higher cytolytic capacity of this subset. Therefore porcine splenic NKp46(high) NK cells represent a highly activated subset of NK cells and may play a profound role in the immune surveillance of this organ.",2013 Mar 1,"['Mair, Kerstin H', 'Müllebner, Andrea', 'Essler, Sabine E', 'Duvigneau, J Catharina', 'Storset, Anne K', 'Saalmüller, Armin', 'Gerner, Wilhelm']",Vet Res,,,True
55648aad5bf29ad5e0eb50642764ff632d95843f,PMC,Porcine CD8α(dim/-)NKp46(high) NK cells are in a highly activated state,http://dx.doi.org/10.1186/1297-9716-44-13,PMC3599810,23452562,CC BY,"Natural Killer (NK) cells play a crucial role in the early phase of immune responses against various pathogens. In swine so far only little information about this lymphocyte population exists. Phenotypical analyses with newly developed monoclonal antibodies (mAbs) against porcine NKp46 recently revealed that in blood NKp46(-) and NKp46(+) cells with NK phenotype exist with comparable cytotoxic properties. In spleen a third NKp46-defined population with NK phenotype was observed that was characterised by a low to negative CD8α and increased NKp46 expression. In the current study it is shown that this NKp46(high) phenotype was correlated with an increased expression of CD16 and CD27 compared to the CD8α(+)NKp46(-) and NKp46(+) NK-cell subsets in spleen and blood. Additionally NKp46(high) NK cells expressed elevated levels of the chemokine receptor CXCR3 on mRNA level. Functional analyses revealed that splenic NKp46(high) NK cells produced much higher levels of Interferon-γ and Tumor Necrosis Factor-α upon stimulation with cytokines or phorbol-12-myristate-13-acetate/Ionomycin compared to the other two subsets. Furthermore, cross-linking of NKp46 by NKp46-specific mAbs led to a superior CD107a expression in the NKp46(high) NK cells, thus indicating a higher cytolytic capacity of this subset. Therefore porcine splenic NKp46(high) NK cells represent a highly activated subset of NK cells and may play a profound role in the immune surveillance of this organ.",2013 Mar 1,"['Mair, Kerstin H', 'Müllebner, Andrea', 'Essler, Sabine E', 'Duvigneau, J Catharina', 'Storset, Anne K', 'Saalmüller, Armin', 'Gerner, Wilhelm']",Vet Res,,,False
0656993afda296004221087271ce7e3dfe596c6c,PMC,Porcine CD8α(dim/-)NKp46(high) NK cells are in a highly activated state,http://dx.doi.org/10.1186/1297-9716-44-13,PMC3599810,23452562,CC BY,"Natural Killer (NK) cells play a crucial role in the early phase of immune responses against various pathogens. In swine so far only little information about this lymphocyte population exists. Phenotypical analyses with newly developed monoclonal antibodies (mAbs) against porcine NKp46 recently revealed that in blood NKp46(-) and NKp46(+) cells with NK phenotype exist with comparable cytotoxic properties. In spleen a third NKp46-defined population with NK phenotype was observed that was characterised by a low to negative CD8α and increased NKp46 expression. In the current study it is shown that this NKp46(high) phenotype was correlated with an increased expression of CD16 and CD27 compared to the CD8α(+)NKp46(-) and NKp46(+) NK-cell subsets in spleen and blood. Additionally NKp46(high) NK cells expressed elevated levels of the chemokine receptor CXCR3 on mRNA level. Functional analyses revealed that splenic NKp46(high) NK cells produced much higher levels of Interferon-γ and Tumor Necrosis Factor-α upon stimulation with cytokines or phorbol-12-myristate-13-acetate/Ionomycin compared to the other two subsets. Furthermore, cross-linking of NKp46 by NKp46-specific mAbs led to a superior CD107a expression in the NKp46(high) NK cells, thus indicating a higher cytolytic capacity of this subset. Therefore porcine splenic NKp46(high) NK cells represent a highly activated subset of NK cells and may play a profound role in the immune surveillance of this organ.",2013 Mar 1,"['Mair, Kerstin H', 'Müllebner, Andrea', 'Essler, Sabine E', 'Duvigneau, J Catharina', 'Storset, Anne K', 'Saalmüller, Armin', 'Gerner, Wilhelm']",Vet Res,,,False
eb5f4f63cdb4bfd57256d362dbd01063522c9f05,PMC,A mixed integer linear programming model to reconstruct phylogenies from single nucleotide polymorphism haplotypes under the maximum parsimony criterion,http://dx.doi.org/10.1186/1748-7188-8-3,PMC3599976,23343437,CC BY,"BACKGROUND: Phylogeny estimation from aligned haplotype sequences has attracted more and more attention in the recent years due to its importance in analysis of many fine-scale genetic data. Its application fields range from medical research, to drug discovery, to epidemiology, to population dynamics. The literature on molecular phylogenetics proposes a number of criteria for selecting a phylogeny from among plausible alternatives. Usually, such criteria can be expressed by means of objective functions, and the phylogenies that optimize them are referred to as optimal. One of the most important estimation criteria is the parsimony which states that the optimal phylogeny T(∗)for a set [Formula: see text] of n haplotype sequences over a common set of variable loci is the one that satisfies the following requirements: (i) it has the shortest length and (ii) it is such that, for each pair of distinct haplotypes [Formula: see text] , the sum of the edge weights belonging to the path from h(i) to h(j) in T(∗) is not smaller than the observed number of changes between h(i) and h(j). Finding the most parsimonious phylogeny for [Formula: see text] involves solving an optimization problem, called the Most Parsimonious Phylogeny Estimation Problem (MPPEP), which is [Formula: see text]-hard in many of its versions. RESULTS: In this article we investigate a recent version of the MPPEP that arises when input data consist of single nucleotide polymorphism haplotypes extracted from a population of individuals on a common genomic region. Specifically, we explore the prospects for improving on the implicit enumeration strategy of implicit enumeration strategy used in previous work using a novel problem formulation and a series of strengthening valid inequalities and preliminary symmetry breaking constraints to more precisely bound the solution space and accelerate implicit enumeration of possible optimal phylogenies. We present the basic formulation and then introduce a series of provable valid constraints to reduce the solution space. We then prove that these constraints can often lead to significant reductions in the gap between the optimal solution and its non-integral linear programming bound relative to the prior art as well as often substantially faster processing of moderately hard problem instances. CONCLUSION: We provide an indication of the conditions under which such an optimal enumeration approach is likely to be feasible, suggesting that these strategies are usable for relatively large numbers of taxa, although with stricter limits on numbers of variable sites. The work thus provides methodology suitable for provably optimal solution of some harder instances that resist all prior approaches.",2013 Jan 23,"['Catanzaro, Daniele', 'Ravi, Ramamoorthi', 'Schwartz, Russell']",Algorithms Mol Biol,,,True
74d9a4215dd1ab6d78bd9b6dbd2dc096c974cf4b,PMC,A novel coronavirus capable of lethal human infections: an emerging picture,http://dx.doi.org/10.1186/1743-422X-10-66,PMC3599982,23445530,CC BY,"SUMMARY: In September 2012, a novel coronavirus was isolated from a patient in Saudi Arabia who had died of an acute respiratory illness and renal failure. The clinical presentation was reminiscent of the outbreak caused by the SARS-coronavirus (SARS-CoV) exactly ten years ago that resulted in over 8000 cases. Sequence analysis of the new virus revealed that it was indeed a member of the same genus as SARS-CoV. By mid-February 2013, 12 laboratory-confirmed cases had been reported with 6 fatalities. The first 9 cases were in individuals resident in the Middle East, while the most recent 3 cases were in family members resident in the UK. The index case in the UK family cluster had travel history to Pakistan and Saudi Arabia. Although the current evidence suggests that this virus is not highly transmissible among humans, there is a real danger that it may spread to other parts of the world. Here, a brief review of the events is provided to summarize the rapidly emerging picture of this new virus.",2013 Feb 28,"Khan, Gulfaraz",Virol J,,,True
3fee471a12aa3fbfc3abab41a0f2604906c8acf0,PMC,Ecology of Zoonotic Infectious Diseases in Bats: Current Knowledge and Future Directions,http://dx.doi.org/10.1111/zph.12000,PMC3600532,22958281,CC BY,"Bats are hosts to a range of zoonotic and potentially zoonotic pathogens. Human activities that increase exposure to bats will likely increase the opportunity for infections to spill over in the future. Ecological drivers of pathogen spillover and emergence in novel hosts, including humans, involve a complex mixture of processes, and understanding these complexities may aid in predicting spillover. In particular, only once the pathogen and host ecologies are known can the impacts of anthropogenic changes be fully appreciated. Cross-disciplinary approaches are required to understand how host and pathogen ecology interact. Bats differ from other sylvatic disease reservoirs because of their unique and diverse lifestyles, including their ability to fly, often highly gregarious social structures, long lifespans and low fecundity rates. We highlight how these traits may affect infection dynamics and how both host and pathogen traits may interact to affect infection dynamics. We identify key questions relating to the ecology of infectious diseases in bats and propose that a combination of field and laboratory studies are needed to create data-driven mechanistic models to elucidate those aspects of bat ecology that are most critical to the dynamics of emerging bat viruses. If commonalities can be found, then predicting the dynamics of newly emerging diseases may be possible. This modelling approach will be particularly important in scenarios when population surveillance data are unavailable and when it is unclear which aspects of host ecology are driving infection dynamics.",2013 Feb,"['Hayman, D T S', 'Bowen, R A', 'Cryan, P M', 'McCracken, G F', 'O’Shea, T J', 'Peel, A J', 'Gilbert, A', 'Webb, C T', 'Wood, J L N']",Zoonoses Public Health,,,True
ab5652086c345dbe360ca35b48b31e43f95507e4,PMC,Reactomes of Porcine Alveolar Macrophages Infected with Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1371/journal.pone.0059229,PMC3602036,23527143,CC0,"Porcine reproductive and respiratory syndrome (PRRS) has devastated pig industries worldwide for many years. It is caused by a small RNA virus (PRRSV), which targets almost exclusively pig monocytes or macrophages. In the present study, five SAGE (serial analysis of gene expression) libraries derived from 0 hour mock-infected and 6, 12, 16 and 24 hours PRRSV-infected porcine alveolar macrophages (PAMs) produced a total 643,255 sequenced tags with 91,807 unique tags. Differentially expressed (DE) tags were then detected using the Bayesian framework followed by gene/mRNA assignment, arbitrary selection and manual annotation, which determined 699 DE genes for reactome analysis. The DAVID, KEGG and REACTOME databases assigned 573 of the DE genes into six biological systems, 60 functional categories and 504 pathways. The six systems are: cellular processes, genetic information processing, environmental information processing, metabolism, organismal systems and human diseases as defined by KEGG with modification. Self-organizing map (SOM) analysis further grouped these 699 DE genes into ten clusters, reflecting their expression trends along these five time points. Based on the number one functional category in each system, cell growth and death, transcription processes, signal transductions, energy metabolism, immune system and infectious diseases formed the major reactomes of PAMs responding to PRRSV infection. Our investigation also focused on dominant pathways that had at least 20 DE genes identified, multi-pathway genes that were involved in 10 or more pathways and exclusively-expressed genes that were included in one system. Overall, our present study reported a large set of DE genes, compiled a comprehensive coverage of pathways, and revealed system-based reactomes of PAMs infected with PRRSV. We believe that our reactome data provides new insight into molecular mechanisms involved in host genetic complexity of antiviral activities against PRRSV and lays a strong foundation for vaccine development to control PRRS incidence in pigs.",2013 Mar 19,"['Jiang, Zhihua', 'Zhou, Xiang', 'Michal, Jennifer J.', 'Wu, Xiao-Lin', 'Zhang, Lifan', 'Zhang, Ming', 'Ding, Bo', 'Liu, Bang', 'Manoranjan, Valipuram S.', 'Neill, John D.', 'Harhay, Gregory P.', 'Kehrli, Marcus E.', 'Miller, Laura C.']",PLoS One,,,True
11855c4ce9640d35da8dd4c54e913843a41c9252,PMC,"Prospective surveillance study of acute respiratory infections, influenza-like illness and seasonal influenza vaccine in a cohort of juvenile idiopathic arthritis patients",http://dx.doi.org/10.1186/1546-0096-11-10,PMC3602114,23510667,CC BY,"BACKGROUND: Acute respiratory infections (ARI) are frequent in children and complications can occur in patients with chronic diseases. We evaluated the frequency and impact of ARI and influenza-like illness (ILI) episodes on disease activity, and the immunogenicity and safety of influenza vaccine in a cohort of juvenile idiopathic arthritis (JIA) patients. METHODS: Surveillance of respiratory viruses was conducted in JIA patients during ARI season (March to August) in two consecutive years: 2007 (61 patients) and 2008 (63 patients). Patients with ARI or ILI had respiratory samples collected for virus detection by real time PCR. In 2008, 44 patients were immunized with influenza vaccine. JIA activity index (ACRPed30) was assessed during both surveillance periods. Influenza hemagglutination inhibition antibody titers were measured before and 30-40 days after vaccination. RESULTS: During the study period 105 ARI episodes were reported and 26.6% of them were ILI. Of 33 samples collected, 60% were positive for at least one virus. Influenza and rhinovirus were the most frequently detected, in 30% of the samples. Of the 50 JIA flares observed, 20% were temporally associated to ARI. Influenza seroprotection rates were higher than 70% (91-100%) for all strains, and seroconversion rates exceeded 40% (74-93%). In general, response to influenza vaccine was not influenced by therapy or disease activity, but patients using anti-TNF alpha drugs presented lower seroconversion to H1N1 strain. No significant differences were found in ACRPed30 after vaccination and no patient reported ILI for 6 months after vaccination. CONCLUSION: ARI episodes are relatively frequent in JIA patients and may have a role triggering JIA flares. Trivalent split influenza vaccine seems to be immunogenic and safe in JIA patients.",2013 Mar 7,"['Carvalho, Luciana M', 'de Paula, Flávia E', 'Silvestre, Rodrigo V D', 'Roberti, Luciana R', 'Arruda, Eurico', 'Mello, Wyller A', 'Ferriani, Virginia P L']",Pediatr Rheumatol Online J,,,True
d5076ff3eb3e96c862345fa109990f9a7b99b842,PMC,Evaluation on the Efficacy and Immunogenicity of Recombinant DNA Plasmids Expressing Spike Genes from Porcine Transmissible Gastroenteritis Virus and Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.1371/journal.pone.0057468,PMC3602451,23526943,CC BY,"Porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PDEV) can cause severe diarrhea in pigs. Development of effective vaccines against TGEV and PEDV is one of important prevention measures. The spike (S) protein is the surface glycoprotein of TGEV and PEDV, which can induce specific neutralization antibodies and is a candidate antigen for vaccination attempts. In this study, the open reading frames of the TGEV S1 protein and in addition of the S or S1 proteins of PEDV were inserted into the eukaryotic expression vector, pIRES, resulting in recombinant plasmids, pIRES-(TGEV-S1-PEDV-S1) and pIRES-(TGEV-S1-PEDV-S). Subsequently, 6–8 weeks old Kunming mice were inoculated with both DNA plasmids. Lymphocyte proliferation assay, virus neutralization assay, IFN-γ assay and CTL activity assay were performed. TGEV/PEDV specific antibody responses as well as kinetic changes of T lymphocyte subgroups of the immunized mice were analyzed. The results showed that the recombinant DNA plasmids increased the proliferation of T lymphocytes and the number of CD4+ and CD8+ T lymphocyte subgroups. In addition, the DNA vaccines induced a high level of IFN-γ in the immunized mice. The specific CTL activity in the pIRES-(TGEV-S1-PEDV-S) group became significant at 42 days post-immunization. At 35 days post-immunization, the recombinant DNA plasmids bearing full-length S genes of TGEV and PEDV stimulated higher levels of specific antibodies and neutralizing antibodies in immunized mice.",2013 Mar 19,"['Meng, Fandan', 'Ren, Yudong', 'Suo, Siqingaowa', 'Sun, Xuejiao', 'Li, Xunliang', 'Li, Pengchong', 'Yang, Wei', 'Li, Guangxing', 'Li, Lu', 'Schwegmann-Wessels, Christel', 'Herrler, Georg', 'Ren, Xiaofeng']",PLoS One,,,True
8620ebc72710ffd02328954e8447585ffcb5cae2,PMC,Role of Antidiarrhoeal Drugs as Adjunctive Therapies for Acute Diarrhoea in Children,http://dx.doi.org/10.1155/2013/612403,PMC3603675,23533446,CC BY,"Acute diarrhoea is a leading cause of child mortality in developing countries. Principal pathogens include Escherichia coli, rotaviruses, and noroviruses. 90% of diarrhoeal deaths are attributable to inadequate sanitation. Acute diarrhoea is the second leading cause of overall childhood mortality and accounts for 18% of deaths among children under five. In 2004 an estimated 1.5 million children died from diarrhoea, with 80% of deaths occurring before the age of two. Treatment goals are to prevent dehydration and nutritional damage and to reduce duration and severity of diarrhoeal episodes. The recommended therapeutic regimen is to provide oral rehydration solutions (ORS) and to continue feeding. Although ORS effectively mitigates dehydration, it has no effect on the duration, severity, or frequency of diarrhoeal episodes. Adjuvant therapy with micronutrients, probiotics, or antidiarrhoeal agents may thus be useful. The WHO recommends the use of zinc tablets in association with ORS. The ESPGHAN/ESPID treatment guidelines consider the use of racecadotril, diosmectite, or probiotics as possible adjunctive therapy to ORS. Only racecadotril and diosmectite reduce stool output, but no treatment has yet been shown to reduce hospitalisation rate or mortality. Appropriate management with validated treatments may help reduce the health and economic burden of acute diarrhoea in children worldwide.",2013 Mar 3,"Faure, Christophe",Int J Pediatr,,,True
f65cdf4a48c1ad11e613449dad480736e9d26945,PMC,Snapshot of Viral Infections in Wild Carnivores Reveals Ubiquity of Parvovirus and Susceptibility of Egyptian Mongoose to Feline Panleukopenia Virus,http://dx.doi.org/10.1371/journal.pone.0059399,PMC3603882,23527182,CC BY,"The exposure of wild carnivores to viral pathogens, with emphasis on parvovirus (CPV/FPLV), was assessed based on the molecular screening of tissue samples from 128 hunted or accidentally road-killed animals collected in Portugal from 2008 to 2011, including Egyptian mongoose (Herpestes ichneumon, n = 99), red fox (Vulpes vulpes, n = 19), stone marten (Martes foina, n = 3), common genet (Genetta genetta, n = 3) and Eurasian badger (Meles meles, n = 4). A high prevalence of parvovirus DNA (63%) was detected among all surveyed species, particularly in mongooses (58%) and red foxes (79%), along with the presence of CPV/FPLV circulating antibodies that were identified in 90% of a subset of parvovirus-DNA positive samples. Most specimens were extensively autolysed, restricting macro and microscopic investigations for lesion evaluation. Whenever possible to examine, signs of active disease were not present, supporting the hypothesis that the parvovirus vp2 gene fragments detected by real-time PCR possibly correspond to viral DNA reminiscent from previous infections. The molecular characterization of viruses, based on the analysis of the complete or partial sequence of the vp2 gene, allowed typifying three viral strains of mongoose and four red fox’s as feline panleukopenia virus (FPLV) and one stone marten’s as newCPV-2b type. The genetic similarity found between the FPLV viruses from free-ranging and captive wild species originated in Portugal and publicly available comparable sequences, suggests a closer genetic relatedness among FPLV circulating in Portugal. Although the clinical and epidemiological significance of infection could not be established, this study evidences that exposure of sympatric wild carnivores to parvovirus is common and geographically widespread, potentially carrying a risk to susceptible populations at the wildlife-domestic interface and to threatened species, such as the wildcat (Felis silvestris) and the critically endangered Iberian lynx (Lynx pardinus).",2013 Mar 20,"['Duarte, Margarida D.', 'Henriques, Ana Margarida', 'Barros, Sílvia Carla', 'Fagulha, Teresa', 'Mendonça, Paula', 'Carvalho, Paulo', 'Monteiro, Madalena', 'Fevereiro, Miguel', 'Basto, Mafalda P.', 'Rosalino, Luís Miguel', 'Barros, Tânia', 'Bandeira, Victor', 'Fonseca, Carlos', 'Cunha, Mónica V.']",PLoS One,,,True
f8290fc7f4fb355f1da52f816acfb2113691acb3,PMC,Retroviral and Lentiviral Vectors for the Induction of Immunological Tolerance,http://dx.doi.org/10.6064/2012/694137,PMC3605697,23526794,CC BY,"Retroviral and lentiviral vectors have proven to be particularly efficient systems to deliver genes of interest into target cells, either in vivo or in cell cultures. They have been used for some time for gene therapy and the development of gene vaccines. Recently retroviral and lentiviral vectors have been used to generate tolerogenic dendritic cells, key professional antigen presenting cells that regulate immune responses. Thus, three main approaches have been undertaken to induce immunological tolerance; delivery of potent immunosuppressive cytokines and other molecules, modification of intracellular signalling pathways in dendritic cells, and de-targeting transgene expression from dendritic cells using microRNA technology. In this review we briefly describe retroviral and lentiviral vector biology, and their application to induce immunological tolerance.",2012 Jul 18,"['Dufait, Inès', 'Liechtenstein, Therese', 'Lanna, Alessio', 'Bricogne, Christopher', 'Laranga, Roberta', 'Padella, Antonella', 'Breckpot, Karine', 'Escors, David']",Scientifica (Cairo),,,True
5ea028a50ee04aafff0b50ed954a3337176eca1b,PMC,Infiltration of Proinflammatory M1 Macrophages into the Outer Retina Precedes Damage in a Mouse Model of Age-Related Macular Degeneration,http://dx.doi.org/10.1155/2013/503725,PMC3606733,23533946,CC BY,"Age-related macular degeneration (AMD) is a major cause of blindness in the developed world. Oxidative stress and inflammation are implicated in AMD, but precise mechanisms remain poorly defined. Carboxyethylpyrrole (CEP) is an AMD-associated lipid peroxidation product. We previously demonstrated that mice immunized with CEP-modified albumin developed AMD-like degenerative changes in the outer retina. Here, we examined the kinetics of lesion development in immunized mice and the presence of macrophages within the interphotoreceptor matrix (IPM), between the retinal pigment epithelium and photoreceptor outer segments. We observed a significant and time-dependent increase in the number of macrophages in immunized mice relative to young age-matched controls prior to overt pathology. These changes were more pronounced in BALB/c mice than in C57BL/6 mice. Importantly, IPM-infiltrating macrophages were polarized toward the M1 phenotype but only in immunized mice. Moreover, when Ccr2-deficient mice were immunized, macrophages were not present in the IPM and no retinal lesions were observed, suggesting a deleterious role for these cells in our model. This work provides mechanistic evidence linking immune responses against oxidative damage with the presence of proinflammatory macrophages at sites of future AMD and experimentally demonstrates that manipulating immunity may be a target for modulating the development of AMD.",2013 Mar 7,"['Cruz-Guilloty, Fernando', 'Saeed, Ali M.', 'Echegaray, Jose J.', 'Duffort, Stephanie', 'Ballmick, Asha', 'Tan, Yaohong', 'Betancourt, Michel', 'Viteri, Eduardo', 'Ramkhellawan, Ghansham C.', 'Ewald, Eric', 'Feuer, William', 'Huang, DeQiang', 'Wen, Rong', 'Hong, Li', 'Wang, Hua', 'Laird, James M.', 'Sene, Abdoulaye', 'Apte, Rajendra S.', 'Salomon, Robert G.', 'Hollyfield, Joe G.', 'Perez, Victor L.']",Int J Inflam,,,False
d08ac6ac9dd268022b8cbe5cba116dd2bd12f757,PMC,Infiltration of Proinflammatory M1 Macrophages into the Outer Retina Precedes Damage in a Mouse Model of Age-Related Macular Degeneration,http://dx.doi.org/10.1155/2013/503725,PMC3606733,23533946,CC BY,"Age-related macular degeneration (AMD) is a major cause of blindness in the developed world. Oxidative stress and inflammation are implicated in AMD, but precise mechanisms remain poorly defined. Carboxyethylpyrrole (CEP) is an AMD-associated lipid peroxidation product. We previously demonstrated that mice immunized with CEP-modified albumin developed AMD-like degenerative changes in the outer retina. Here, we examined the kinetics of lesion development in immunized mice and the presence of macrophages within the interphotoreceptor matrix (IPM), between the retinal pigment epithelium and photoreceptor outer segments. We observed a significant and time-dependent increase in the number of macrophages in immunized mice relative to young age-matched controls prior to overt pathology. These changes were more pronounced in BALB/c mice than in C57BL/6 mice. Importantly, IPM-infiltrating macrophages were polarized toward the M1 phenotype but only in immunized mice. Moreover, when Ccr2-deficient mice were immunized, macrophages were not present in the IPM and no retinal lesions were observed, suggesting a deleterious role for these cells in our model. This work provides mechanistic evidence linking immune responses against oxidative damage with the presence of proinflammatory macrophages at sites of future AMD and experimentally demonstrates that manipulating immunity may be a target for modulating the development of AMD.",2013 Mar 7,"['Cruz-Guilloty, Fernando', 'Saeed, Ali M.', 'Echegaray, Jose J.', 'Duffort, Stephanie', 'Ballmick, Asha', 'Tan, Yaohong', 'Betancourt, Michel', 'Viteri, Eduardo', 'Ramkhellawan, Ghansham C.', 'Ewald, Eric', 'Feuer, William', 'Huang, DeQiang', 'Wen, Rong', 'Hong, Li', 'Wang, Hua', 'Laird, James M.', 'Sene, Abdoulaye', 'Apte, Rajendra S.', 'Salomon, Robert G.', 'Hollyfield, Joe G.', 'Perez, Victor L.']",Int J Inflam,,,True
5315d146c36ec79e45765ebf95759cfcad3a9f84,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,True
55ae9f78b75de806bbf7a4cc9f9b5e1d555f3b49,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
0a28e83bc38bca29c3fb0b446a346485c56c37ab,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
53d0e3f0cfe8c7e1f3d52a1c5a21a9ef62bf8d8e,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
09bb90a9f2bf8c12df5525b81a95b700d6096071,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
45a0829c6f38d9f4ea6321b844225743e8c7401d,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
d7222bc85d41d9bc5487ed14c5a070121a5dfa4a,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
ddff9be96a1c643fdc8d5dca5c5eaf2f537d9df5,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
84bd712908ff75807c275e8947b8ae96797f7c67,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
f795c7726f9ec87a62ddb0f2b23c9500a15b92db,PMC,Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker,http://dx.doi.org/10.1371/journal.pone.0057911,PMC3607594,23536776,CC BY,"BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.",2013 Mar 25,"['Rachidi, Saleh M.', 'Qin, Tingting', 'Sun, Shaoli', 'Zheng, W. Jim', 'Li, Zihai']",PLoS One,,,False
9ab49a277ef0a3a15aba628771a22b8c2af6ede0,PMC,Genetic recombination in plant-infecting messenger-sense RNA viruses: overview and research perspectives,http://dx.doi.org/10.3389/fpls.2013.00068,PMC3607795,23533000,CC BY,"RNA recombination is one of the driving forces of genetic variability in (+)-strand RNA viruses. Various types of RNA–RNA crossovers were described including crosses between the same or different viral RNAs or between viral and cellular RNAs. Likewise, a variety of molecular mechanisms are known to support RNA recombination, such as replicative events (based on internal or end-to-end replicase switchings) along with non-replicative joining among RNA fragments of viral and/or cellular origin. Such mechanisms as RNA decay or RNA interference are responsible for RNA fragmentation and trans-esterification reactions which are likely accountable for ligation of RNA fragments. Numerous host factors were found to affect the profiles of viral RNA recombinants and significant differences in recombination frequency were observed among various RNA viruses. Comparative analyses of viral sequences allowed for the development of evolutionary models in order to explain adaptive phenotypic changes and co-evolving sites. Many questions remain to be answered by forthcoming RNA recombination research. (1) How various factors modulate the ability of viral replicase to switch templates, (2) What is the intracellular location of RNA–RNA template switchings, (3) Mechanisms and factors responsible for non-replicative RNA recombination, (4) Mechanisms of integration of RNA viral sequences with cellular genomic DNA, and (5) What is the role of RNA splicing and ribozyme activity. From an evolutionary stand point, it is not known how RNA viruses parasitize new host species via recombination, nor is it obvious what the contribution of RNA recombination is among other RNA modification pathways. We do not understand why the frequency of RNA recombination varies so much among RNA viruses and the status of RNA recombination as a form of sex is not well documented.",2013 Mar 26,"Bujarski, Jozef J.",Front Plant Sci,,,True
ecd247bf710a751792bb6ca40d0b8bcacf2d56ee,PMC,"ciliaFA: a research tool for automated, high-throughput measurement of ciliary beat frequency using freely available software",http://dx.doi.org/10.1186/2046-2530-1-14,PMC3607980,23351276,CC BY,"BACKGROUND: Analysis of ciliary function for assessment of patients suspected of primary ciliary dyskinesia (PCD) and for research studies of respiratory and ependymal cilia requires assessment of both ciliary beat pattern and beat frequency. While direct measurement of beat frequency from high-speed video recordings is the most accurate and reproducible technique it is extremely time consuming. The aim of this study was to develop a freely available automated method of ciliary beat frequency analysis from digital video (AVI) files that runs on open-source software (ImageJ) coupled to Microsoft Excel, and to validate this by comparison to the direct measuring high-speed video recordings of respiratory and ependymal cilia. These models allowed comparison to cilia beating between 3 and 52 Hz. METHODS: Digital video files of motile ciliated ependymal (frequency range 34 to 52 Hz) and respiratory epithelial cells (frequency 3 to 18 Hz) were captured using a high-speed digital video recorder. To cover the range above between 18 and 37 Hz the frequency of ependymal cilia were slowed by the addition of the pneumococcal toxin pneumolysin. Measurements made directly by timing a given number of individual ciliary beat cycles were compared with those obtained using the automated ciliaFA system. RESULTS: The overall mean difference (± SD) between the ciliaFA and direct measurement high-speed digital imaging methods was −0.05 ± 1.25 Hz, the correlation coefficient was shown to be 0.991 and the Bland-Altman limits of agreement were from −1.99 to 1.49 Hz for respiratory and from −2.55 to 3.25 Hz for ependymal cilia. CONCLUSIONS: A plugin for ImageJ was developed that extracts pixel intensities and performs fast Fourier transformation (FFT) using Microsoft Excel. The ciliaFA software allowed automated, high throughput measurement of respiratory and ependymal ciliary beat frequency (range 3 to 52 Hz) and avoids operator error due to selection bias. We have included free access to the ciliaFA plugin and installation instructions in Additional file 1 accompanying this manuscript that other researchers may use.",2012 Aug 1,"['Smith, Claire M', 'Djakow, Jana', 'Free, Robert C', 'Djakow, Petr', 'Lonnen, Rana', 'Williams, Gwyneth', 'Pohunek, Petr', 'Hirst, Robert A', 'Easton, Andrew J', 'Andrew, Peter W', 'O’Callaghan, Christopher']",Cilia,,,True
5ff8a6df6aa6e3ec16db9ff91702f691c18541df,PMC,Interaction of Bordetella bronchiseptica and Its Lipopolysaccharide with In Vitro Culture of Respiratory Nasal Epithelium,http://dx.doi.org/10.1155/2013/347086,PMC3608130,23555071,CC BY,"The nasal septa of fetal rabbits at 26 days of gestation were harvested by cesarean section of the does while under anesthesia and then exposed to Bordetella bronchiseptica or its lipopolysaccharide (LPS) for periods of 2 and 4 hours. A total of 240 explants were used. The tissues were examined using the Hematoxylin & Eosin technique. Then, semithin sections (0.5 μm) were stained with toluidine blue and examined with indirect immunoperoxidase (IPI) and lectin histochemistry. The most frequent and statistically significant findings were as follows: (1) cell death and increased goblet cell activity when exposed to bacteria and (2) cell death, cytoplasmic vacuolation and infiltration of polymorphonuclear leukocytes when exposed to LPS. The lesions induced by the bacterium were more severe than with LPS alone, except for the cytoplasmic vacuolation in epithelial cells. IPI stained the ciliated border of the epithelium with the bacterium more intensely, while LPS lectin histochemistry preferentially labeled the cytoplasm of goblet cell. These data indicate that B. bronchiseptica and its LPS may have an affinity for specific glycoproteins that would act as adhesion receptors in both locations.",2013 Mar 11,"['Gallego, Carolina', 'Middleton, Andrew M.', 'Martínez, Nhora', 'Romero, Stefany', 'Iregui, Carlos']",Vet Med Int,,,True
00951716e01c8e0cc341770389fc38d1b5455210,PMC,"Knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among urban high-risk groups: findings of a cross-sectional study in Dhaka, Bangladesh",http://dx.doi.org/10.1186/1471-2458-13-242,PMC3608226,23509860,CC BY,"BACKGROUND: In endemic countries such as Bangladesh, consequences of cholera place an enormous financial and social burden on patients and their families. Cholera vaccines not only provide health benefits to susceptible populations but also have effects on the earning capabilities and financial stability of the family. Community-based research and evaluations are necessary to understand perceptions about and practices of the community relating to cholera and oral cholera vaccines. This may help identify the ways in which such vaccines may be successfully introduced, and other preventive measures can be implemented. The present study assessed the knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among an urban population residing in a high cholera-prone setting in Dhaka, Bangladesh. METHODS: This cross-sectional study was conducted in an area of high cholera prevalence in 15 randomly-selected clusters in Mirpur, Dhaka city. A study team collected data through a survey and in-depth interviews during December 2010–February 2011. RESULTS: Of 2,830 families included in the final analysis, 23% could recognize cholera as acute watery diarrhea and 16% had ever heard of oral cholera vaccine. About 54% of the respondents had poor knowledge about cholera-related issues while 97% had a positive attitude toward cholera and oral cholera vaccine. One-third showed poor practice relating to the prevention of cholera. The findings showed a significant (p < 0.05) association between the respondents’ knowledge and sex, education, occupation, monthly overall household expenditure, attitudes and practice. In the adjusted model, male sex, having a lower monthly overall household expenditure, and having a less positive attitude toward cholera were the significant predictors to having poor knowledge. CONCLUSIONS: The findings suggest the strengthening of health education activities to improve knowledge on cholera, its prevention and treatment and information on cholera vaccination among high-risk populations. The data also underscore the potential of mass cholera vaccination to prevent and control cholera.",2013 Mar 19,"['Wahed, Tasnuva', 'Kaukab, Sheikh Shah Tanvir', 'Saha, Nirod Chandra', 'Khan, Iqbal Ansary', 'Khanam, Farhana', 'Chowdhury, Fahima', 'Saha, Amit', 'Khan, Ashraful Islam', 'Siddik, Ashraf Uddin', 'Cravioto, Alejandro', 'Qadri, Firdausi', 'Uddin, Jasim']",BMC Public Health,,,True
da9d4dfbed4a51ec017add0fe198ec753807f73a,PMC,"Knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among urban high-risk groups: findings of a cross-sectional study in Dhaka, Bangladesh",http://dx.doi.org/10.1186/1471-2458-13-242,PMC3608226,23509860,CC BY,"BACKGROUND: In endemic countries such as Bangladesh, consequences of cholera place an enormous financial and social burden on patients and their families. Cholera vaccines not only provide health benefits to susceptible populations but also have effects on the earning capabilities and financial stability of the family. Community-based research and evaluations are necessary to understand perceptions about and practices of the community relating to cholera and oral cholera vaccines. This may help identify the ways in which such vaccines may be successfully introduced, and other preventive measures can be implemented. The present study assessed the knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among an urban population residing in a high cholera-prone setting in Dhaka, Bangladesh. METHODS: This cross-sectional study was conducted in an area of high cholera prevalence in 15 randomly-selected clusters in Mirpur, Dhaka city. A study team collected data through a survey and in-depth interviews during December 2010–February 2011. RESULTS: Of 2,830 families included in the final analysis, 23% could recognize cholera as acute watery diarrhea and 16% had ever heard of oral cholera vaccine. About 54% of the respondents had poor knowledge about cholera-related issues while 97% had a positive attitude toward cholera and oral cholera vaccine. One-third showed poor practice relating to the prevention of cholera. The findings showed a significant (p < 0.05) association between the respondents’ knowledge and sex, education, occupation, monthly overall household expenditure, attitudes and practice. In the adjusted model, male sex, having a lower monthly overall household expenditure, and having a less positive attitude toward cholera were the significant predictors to having poor knowledge. CONCLUSIONS: The findings suggest the strengthening of health education activities to improve knowledge on cholera, its prevention and treatment and information on cholera vaccination among high-risk populations. The data also underscore the potential of mass cholera vaccination to prevent and control cholera.",2013 Mar 19,"['Wahed, Tasnuva', 'Kaukab, Sheikh Shah Tanvir', 'Saha, Nirod Chandra', 'Khan, Iqbal Ansary', 'Khanam, Farhana', 'Chowdhury, Fahima', 'Saha, Amit', 'Khan, Ashraful Islam', 'Siddik, Ashraf Uddin', 'Cravioto, Alejandro', 'Qadri, Firdausi', 'Uddin, Jasim']",BMC Public Health,,,False
54fb720924d357327cedcc8da45b5e0ceb5a0006,PMC,"A Laboratory Evaluation of Medicinal Herbs Used in China for the Treatment of Hand, Foot, and Mouth Disease",http://dx.doi.org/10.1155/2013/504563,PMC3608275,23554831,CC BY,"Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the causative agents of hand, foot, and mouth disease (HFMD). During recent epidemics of HFMD in China, medicinal herbals and preparations containing herbal extracts have demonstrated therapeutic efficacy with relative safety profiles. There have been no microbiological studies to validate their usefulness for HFMD. We selected 12 commonly used herbs for HFMD from government recommended guidelines as well as published reports and tested for their antiviral activity and anti-inflammatory activity. A water extract of Houttuynia cordata Thunb. (HCT) inhibited EV71 infection significantly and was marginally active against CVA16 infection. The IC(50) (concentration to have 50% inhibitory effect) values of HCT against a Fuyang strain and a BrCr strain of EV71 were determined at 8.9 μg/mL and 20.6 μg/mL, respectively. Mentha haplocalyx Briq. (MHB) water extract was active against CVA16, with an IC(50) value of 70.3 μg/mL. The extract did not exhibit activity against EV71 infection. Although the majority of the extracts showed no activity against viral infection, several extracts demonstrated activity in blocking proinflammatory response by viral infection. This study therefore validates the effectiveness of Chinese herbs for HFMD since some formulations containing the correct combination of the herbs can block viral replication as well as proinflammatory response of HFMD.",2013 Mar 10,"['Chen, Xiaoqing', 'Wang, Chunyang', 'Xu, Lanfang', 'Chen, Xiaoshuang', 'Wang, Wei', 'Yang, Guang', 'Tan, Ren Xiang', 'Li, Erguang', 'Jin, Yu']",Evid Based Complement Alternat Med,,,True
b263c0ae8e08257b2d46468d7561dbb7d7d6b6e8,PMC,Detection of human coronaviruses in simultaneously collected stool samples and nasopharyngeal swabs from hospitalized children with acute gastroenteritis,http://dx.doi.org/10.1186/1743-422X-10-46,PMC3610273,23379823,CC BY,"BACKGROUND: Human coronaviruses (HCoVs) are a well-known cause of respiratory infections but their role in gastrointestinal infections is unclear. The objective of our study was to assess the significance of HCoVs in the etiology of acute gastroenteritis (AGE) in children <6 years of age. METHODS: Stool samples and nasopharyngeal (NP) swabs collected from 260 children hospitalized for AGE (160 also had respiratory symptoms) and 157 otherwise healthy control children admitted for elective surgery were tested for the presence of four HCoVs using real time RT-PCR. Registered at ClinicalTrials.gov (reg. NCT00987519). RESULTS: HCoVs were more frequent in patients with AGE than in controls (23/260, 8.8% versus 4/151, 2.6%; odds ratio, OR 3.3; 95% confidence interval, CI 1.3–10.0; P = 0.01). Three of four HCoV-positive members in the control group, asymptomatic when sampled, recalled gastrointestinal or respiratory symptoms within the previous 14 days. In patients with AGE, HCoVs were present in NP samples more often than in stools (22/256, 8.6%, versus 6/260, 2.3%; P = 0.0004). In 5/6 children with HCoVs detected in stools, the viruses were also detected in NP swabs. Patients had a significantly higher probability of HCoV detection in stool (OR 4; 95% CI 1.4–15.3; P = 0.006) and also in stool and/or NP (OR 3.3, 95% CI 1.3–10.0; P = 0.01) than healthy controls. All four HCoVs species were detected in stool and NP samples. CONCLUSIONS: Although HCoVs were more frequently detected in patients with AGE than in the control group, high prevalence of HCoVs in NP swabs compounded by their low occurrence in stool samples and detection of other viruses in stool samples, indicate that HCoVs probably play only a minor role in causing gastrointestinal illness in children <6 years old.",2013 Feb 5,"['Jevšnik, Monika', 'Steyer, Andrej', 'Zrim, Tamara', 'Pokorn, Marko', 'Mrvič, Tatjana', 'Grosek, Štefan', 'Strle, Franc', 'Lusa, Lara', 'Petrovec, Miroslav']",Virol J,,,True
190bc9d8aadbfb5c848ccdb9f4fa98610780ba56,PMC,Saikosaponin-d Enhances the Anticancer Potency of TNF-α via Overcoming Its Undesirable Response of Activating NF-Kappa B Signalling in Cancer Cells,http://dx.doi.org/10.1155/2013/745295,PMC3610377,23573150,CC BY,"Tumor necrosis factor-alpha (TNF-α) was reported as anticancer therapy due to its cytotoxic effect against an array of tumor cells. However, its undesirable responses of TNF-α on activating NF-κB signaling and pro-metastatic property limit its clinical application in treating cancers. Therefore, sensitizing agents capable of overcoming this undesirable effect must be valuable for facilitating the usage of TNF-α-mediated apoptosis therapy for cancer patients. Previously, saikosaponin-d (Ssd), a triterpene saponin derived from the medicinal plant, Bupleurum falcatum L. (Umbelliferae), showed to exhibit a variety of pharmacological activities such as antiinflammation, antibacteria, antivirus and anticancer. Recently, we found that Ssd could inhibit the activated T lymphocytes via suppression of NF-κB, NF-AT and AP-1 signaling. Here, we showed that Ssd significantly potentiated TNF-α-mediated cell death in HeLa and HepG2 cancer cells via suppression of TNF-α-induced NF-κB activation and its target genes expression involving cancer cell proliferation, invasion, angiogenesis and survival. Also, Ssd revealed a significant potency of abolishing TNF-α-induced cancer cell invasion and angiogenesis in HUVECs while inducing apoptosis via enhancing the loss of mitochondrial membrane potential in HeLa cells. Collectively, these findings indicate that Ssd has a significant potential to be developed as a combined adjuvant remedy with TNF-α for cancer patients.",2013 Mar 12,"['Wong, Vincent Kam Wai', 'Zhang, Molly Miao', 'Zhou, Hua', 'Lam, Kelly Yin Ching', 'Chan, Po Ling', 'Law, Carmen Ka Man', 'Yue, Patrick Ying Kit', 'Liu, Liang']",Evid Based Complement Alternat Med,,,True
10a769cac0a76b41a6a82be148c1a2675e9d4604,PMC,TIM-family Proteins Promote Infection of Multiple Enveloped Viruses through Virion-associated Phosphatidylserine,http://dx.doi.org/10.1371/journal.ppat.1003232,PMC3610696,23555248,CC BY,"Human T-cell Immunoglobulin and Mucin-domain containing proteins (TIM1, 3, and 4) specifically bind phosphatidylserine (PS). TIM1 has been proposed to serve as a cellular receptor for hepatitis A virus and Ebola virus and as an entry factor for dengue virus. Here we show that TIM1 promotes infection of retroviruses and virus-like particles (VLPs) pseudotyped with a range of viral entry proteins, in particular those from the filovirus, flavivirus, New World arenavirus and alphavirus families. TIM1 also robustly enhanced the infection of replication-competent viruses from the same families, including dengue, Tacaribe, Sindbis and Ross River viruses. All interactions between TIM1 and pseudoviruses or VLPs were PS-mediated, as demonstrated with liposome blocking and TIM1 mutagenesis experiments. In addition, other PS-binding proteins, such as Axl and TIM4, promoted infection similarly to TIM1. Finally, the blocking of PS receptors on macrophages inhibited the entry of Ebola VLPs, suggesting that PS receptors can contribute to infection in physiologically relevant cells. Notably, infection mediated by the entry proteins of Lassa fever virus, influenza A virus and SARS coronavirus was largely unaffected by TIM1 expression. Taken together our data show that TIM1 and related PS-binding proteins promote infection of diverse families of enveloped viruses, and may therefore be useful targets for broad-spectrum antiviral therapies.",2013 Mar 28,"['Jemielity, Stephanie', 'Wang, Jinyize J.', 'Chan, Ying Kai', 'Ahmed, Asim A.', 'Li, Wenhui', 'Monahan, Sheena', 'Bu, Xia', 'Farzan, Michael', 'Freeman, Gordon J.', 'Umetsu, Dale T.', 'DeKruyff, Rosemarie H.', 'Choe, Hyeryun']",PLoS Pathog,,,True
0ac675fdff45bfddf5aea34d37f58ad7df4f78b9,PMC,"Genome and Bioinformatic Analysis of a HAdV-B14p1 Virus Isolated from a Baby with Pneumonia in Beijing, China",http://dx.doi.org/10.1371/journal.pone.0060345,PMC3612040,23555956,CC BY,"The genome of HAdV-B14p1 strain BJ430, isolated from a six-month-old baby diagnosed with bronchial pneumonia at the Beijing Children’s Hospital in December 2010, was sequenced, analyzed, and compared with reference adenovirus genome sequences archived in GenBank. This genome is 34,762 bp in length, remarkably presenting 99.9% identity with the genome from HAdV14p1 strain 303600, which was isolated in the USA (2006). Even more remarkable, it is 99.7% identical with the HAdV-B14p (prototype “de Wit” strain) genome, isolated from The Netherlands in 1955. The patient and its parents presumably had no or limited contact with persons from the USA and Ireland, both of which reported outbreaks of the re-emergent virus HAdV-14p1 recently. These genome data, its analysis, and this report provide a reference for any additional HAdV-B14 outbreak in China and provide the basis for the development of adenovirus vaccines and molecular pathogen surveillance protocols in high-risk areas.",2013 Mar 29,"['Tang, Liuying', 'An, Junjing', 'Xie, Zhengde', 'Dehghan, Shoaleh', 'Seto, Donald', 'Xu, Wenbo', 'Ji, Yixin']",PLoS One,,,True
7722e2866e2b7849cc2f3175430a1048d97b71d9,PMC,Use of Transgenic Animals in Biotechnology: Prospects and Problems,,PMC3612824,23556129,CC BY,"During the past two decades, there have been numerous attempts at using animals in order to produce recombinant human proteins and monoclonal antibodies. However, it is only recently that the first two therapeutic agents isolated from the milk of transgenic animals, C1 inhibitor (Ruconest) and antithrombin (ATryn), appeared on the market. This inspires hope that a considerable number of new recombinant proteins created using such technology could become available for practical use in the near future. In this review, the methods applied to produce transgenic animals are described and the advantages and drawbacks related to their use for producing recombinant human proteins and monoclonal antibodies are discussed.",2013 Jan-Mar,"['Maksimenko, O. G.', 'Deykin, A.V.', 'Khodarovich, Yu. M.', 'Georgiev, P. G.']",Acta Naturae,,,True
d1a0400f1b97c8f05e14aa43796802ccec11f506,PMC,Airflow Dynamics of Human Jets: Sneezing and Breathing - Potential Sources of Infectious Aerosols,http://dx.doi.org/10.1371/journal.pone.0059970,PMC3613375,23560060,CC BY,"Natural human exhalation flows such as coughing, sneezing and breathing can be considered as ‘jet-like’ airflows in the sense that they are produced from a single source in a single exhalation effort, with a relatively symmetrical, conical geometry. Although coughing and sneezing have garnered much attention as potential, explosive sources of infectious aerosols, these are relatively rare events during daily life, whereas breathing is necessary for life and is performed continuously. Real-time shadowgraph imaging was used to visualise and capture high-speed images of healthy volunteers sneezing and breathing (through the nose – nasally, and through the mouth - orally). Six volunteers, who were able to respond to the pepper sneeze stimulus, were recruited for the sneezing experiments (2 women: 27.5±6.36 years; 4 men: 29.25±10.53 years). The maximum visible distance over which the sneeze plumes (or puffs) travelled was 0.6 m, the maximum sneeze velocity derived from these measured distances was 4.5 m/s. The maximum 2-dimensional (2-D) area of dissemination of these sneezes was 0.2 m(2). The corresponding derived parameter, the maximum 2-D area expansion rate of these sneezes was 2 m(2)/s. For nasal breathing, the maximum propagation distance and derived velocity were 0.6 m and 1.4 m/s, respectively. The maximum 2-D area of dissemination and derived expansion rate were 0.11 m(2) and 0.16 m(2)/s, respectively. Similarly, for mouth breathing, the maximum propagation distance and derived velocity were 0.8 m and 1.3 m/s, respectively. The maximum 2-D area of dissemination and derived expansion rate were 0.18 m(2) and 0.17 m(2)/s, respectively. Surprisingly, a comparison of the maximum exit velocities of sneezing reported here with those obtained from coughing (published previously) demonstrated that they are relatively similar, and not extremely high. This is in contrast with some earlier estimates of sneeze velocities, and some reasons for this difference are discussed.",2013 Apr 1,"['Tang, Julian W.', 'Nicolle, Andre D.', 'Klettner, Christian A.', 'Pantelic, Jovan', 'Wang, Liangde', 'Suhaimi, Amin Bin', 'Tan, Ashlynn Y. L.', 'Ong, Garrett W. X.', 'Su, Ruikun', 'Sekhar, Chandra', 'Cheong, David D. W.', 'Tham, Kwok Wai']",PLoS One,,,True
4cb55c99b99ef1944a0b43b342a8bc9eda6ae227,PMC,Strategies to develop antivirals against enterovirus 71,http://dx.doi.org/10.1186/1743-422X-10-28,PMC3614426,23339605,CC BY,"Enterovirus 71 (EV71) is an important human pathogen which may cause severe neurological complications and death in children. The virus caused several outbreaks in the Asia-Pacific region during the past two decades and has been considered a significant public health problem in the post-poliovirus eradication era. Unlike poliovirus, there is no effective vaccine or approved antivirals against EV71. To explore anti-EV71 agents therefore is of vital importance. Several strategies have been employed to develop antivirals based on the molecular characteristics of the virus. Among these, some small molecules that were developed against human rhinoviruses and poliovirus are under evaluation. In this review, we discuss the recent development of such small molecules against EV71, known drug resistance and possible solutions to it, and animal models for evaluating the efficacy of these antivirals. Although further investigation is required for clinical applications of the existing candidates, the molecular mechanisms revealed for the inhibition of EV71 replication can be used for designing new molecules against this virus in the future.",2013 Jan 22,"['Kuo, Rei-Lin', 'Shih, Shin-Ru']",Virol J,,,True
896cfa254a80c192a7aa872d955e750d6280e071,PMC,Seroepidemiological Study on SARS-CoV IgG Antibodies of Different Populations from Several Areas,,PMC3614584,23674957,CC BY,"OBJECTIVE: In order to investigate the clinical and epidemiological rules of severe acute respiratory syndrome (SARS), rates and levels SARS coronavirus (SARS-CoV) IgG antibodies of the patients and community populations from several areas were detected. METHODS: Indirect immunofluorescent assay (IFA) and double-antigen sandwich enzyme-linked immunosorbent assay (ELISA) were used to detect the SARS coronavirus-specific IgG antibodies in sera of 1700, including 1453 general populations from Hongkong, Marco, Guangzhou and Peking and 257 SARS patients from Guangzhou and Peking. The dynamics of the serum antibodies of SARS patients were observed from 3 to 360 days after onset of symptoms. RESULTS: 90% of 257 patient serum specimens after 20 days of disease onset showed positive SARS-CoV IgG either using ELISA or IFA. 257 SARS patients, antibodies titers increased steadily in early 4 to 6 months after onset of SARS. The titers of most cases came to the peak in the 6th month. then antibodies titers declined rapidly in some cases. However, all specimens still were positive for SARS-CoV IgG in the 48th month. CONCLUSIONS: This study suggest that few inapparent infectious patients exist during SARS epidemic. Serum IgG antibodies has diagnostic value for SARS in the late course of disease and the antibodies present more than 48 months.",2005 Jun,"['Shi, Yu-ling', 'Li, Lin-hai', 'Chu, Xin-wei', 'Chen, Qing', 'Wang, Yun-long', 'Ma, Qing-jun', 'Cao, Cheng', 'Yu, Shou-yi']",Int J Biomed Sci,,,True
f0766282327201e2f62b12f14326960106083d73,PMC,Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors,http://dx.doi.org/10.1371/journal.pone.0060838,PMC3614905,23573288,CC BY,"Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes.",2013 Apr 2,"['Brudner, Matthew', 'Karpel, Marshall', 'Lear, Calli', 'Chen, Li', 'Yantosca, L. Michael', 'Scully, Corinne', 'Sarraju, Ashish', 'Sokolovska, Anna', 'Zariffard, M. Reza', 'Eisen, Damon P.', 'Mungall, Bruce A.', 'Kotton, Darrell N.', 'Omari, Amel', 'Huang, I-Chueh', 'Farzan, Michael', 'Takahashi, Kazue', 'Stuart, Lynda', 'Stahl, Gregory L.', 'Ezekowitz, Alan B.', 'Spear, Gregory T.', 'Olinger, Gene G.', 'Schmidt, Emmett V.', 'Michelow, Ian C.']",PLoS One,,,True
15640dc97f36ae7b410f731003235ee8a3cae495,PMC,Downregulation of Signaling-active IGF-1 by Dipeptidyl Peptidase IV (DPP-IV),,PMC3615292,23675206,CC BY,"Functioning as an extracellular protease, dipeptidyl peptidase IV (DPP-IV) preferentially cleaves the peptide bond after the penultimate proline residue. We report here that DPP-IV cleaves the first two amino acids from insulin-like growth factor 1 (IGF-1), revealed by mass spectrometry. The kinetic parameters of the proteolytic cleavage indicate that this reaction is physiologically relevant. Interestingly, truncated IGF-1 is less potent than the full-length protein in activating the IGF-1R, but binds more readily to IGF-binding protein 3 (IGFBP3). Quantitative RT–PCR showed that the level of DPP-IV mRNA is dramatically lower in lung squamous cell carcinoma tissues than in adjacent nonneoplastic lung tissues. However, this reduction was not observed in lung adenocarcinoma tissues. Our study suggests a possible link between IGF-1 and DPP-IV in cancer development in a specific tumor niche. A DPP-IV-related pathway may be important in mitigating IGF-1 signaling. Consequently, a robust IGF signaling pathway may accelerate early carcinogenesis in environments lacking DPP-IV.",2010 Dec,"['Lin, Ching-Ting', 'Tang, Hsiang-Yun', 'Han, Yu-San', 'Liu, Hui-Ping', 'Huang, Shiu-Feng', 'Chien, Chia-Hui', 'Shyy, John', 'Chiu, Jeng-Jian', 'Chen, Xin']",Int J Biomed Sci,,,True
424061f2444cab0c4e972c7fcfc18a9dfbe7b4c6,PMC,Is the reporting timeliness gap for avian flu and H1N1 outbreaks in global health surveillance systems associated with country transparency?,http://dx.doi.org/10.1186/1744-8603-9-14,PMC3615947,23531369,CC BY,"BACKGROUND: This study aims to evaluate the length of time elapsed between reports of the same incidents related to avian flu and H1N1 outbreaks published by the WHO and ProMED-mail, the two major global health surveillance systems, before and after the amendment of the International Health Regulations in 2005 (IHR 2005) and to explore the association between country transparency and this timeliness gap. METHODS: We recorded the initial release dates of each report related to avian flu or H1N1 listed on the WHO Disease Outbreak News site and the matching outbreak report from ProMED-mail, a non-governmental program for monitoring emerging diseases, from 2003 to the end of June 2009. The timeliness gap was calculated as the difference in days between the report release dates of the matching outbreaks in the WHO and ProMED-mail systems. Civil liberties scores were collected as indicators of the transparency of each country. The Human Development Index and data indicating the density of physicians and nurses were collected to reflect countries’ development and health workforce statuses. Then, logistic regression was performed to determine the correlation between the timeliness gap and civil liberties, human development, and health workforce status, controlling for year. RESULTS: The reporting timeliness gap for avian flu and H1N1 outbreaks significantly decreased after 2003. On average, reports were posted 4.09 (SD = 7.99) days earlier by ProMED-mail than by the WHO. Countries with partly free (OR = 5.77) and free civil liberties scores (OR = 10.57) had significantly higher likelihoods of longer timeliness gaps than non-free countries. Similarly, countries with very high human development status had significantly higher likelihoods of longer timeliness gaps than countries with middle or low human development status (OR = 5.30). However, no association between the timeliness gap and health workforce density was found. CONCLUSION: The study found that the adoption of IHR 2005, which contributed to countries’ awareness of the importance of timely reporting, had a significant impact in improving the reporting timeliness gap. In addition, the greater the civil liberties in a country (e.g., importance of freedom of the media), the longer the timeliness gap.",2013 Mar 25,"['Tsai, Feng-Jen', 'Tseng, Eva', 'Chan, Chang-Chuan', 'Tamashiro, Hiko', 'Motamed, Sandrine', 'Rougemont, André C']",Global Health,,,True
e0e5e7bee4a69a83d9cffeefcdcc26172d56f1a4,PMC,Rab11-FIP1C and Rab14 Direct Plasma Membrane Sorting and Particle Incorporation of the HIV-1 Envelope Glycoprotein Complex,http://dx.doi.org/10.1371/journal.ppat.1003278,PMC3616983,23592992,CC BY,"The incorporation of the envelope glycoprotein complex (Env) onto the developing particle is a crucial step in the HIV-1 lifecycle. The long cytoplasmic tail (CT) of Env is required for the incorporation of Env onto HIV particles in T cells and macrophages. Here we identify the Rab11a-FIP1C/RCP protein as an essential cofactor for HIV-1 Env incorporation onto particles in relevant human cells. Depletion of FIP1C reduced Env incorporation in a cytoplasmic tail-dependent manner, and was rescued by replenishment of FIP1C. FIP1C was redistributed out of the endosomal recycling complex to the plasma membrane by wild type Env protein but not by CT-truncated Env. Rab14 was required for HIV-1 Env incorporation, and FIP1C mutants incapable of binding Rab14 failed to rescue Env incorporation. Expression of FIP1C and Rab14 led to an enhancement of Env incorporation, indicating that these trafficking factors are normally limiting for CT-dependent Env incorporation onto particles. These findings support a model for HIV-1 Env incorporation in which specific targeting to the particle assembly microdomain on the plasma membrane is mediated by FIP1C and Rab14.",2013 Apr 4,"['Qi, Mingli', 'Williams, Janice A.', 'Chu, Hin', 'Chen, Xuemin', 'Wang, Jaang-Jiun', 'Ding, Lingmei', 'Akhirome, Ehiole', 'Wen, Xiaoyun', 'Lapierre, Lynne A.', 'Goldenring, James R.', 'Spearman, Paul']",PLoS Pathog,,,True
4278a9b763f17829897dde88a49fcab6ab86b8c7,PMC,Alginic Acid-Coated Chitosan Nanoparticles Loaded with Legumain DNA Vaccine: Effect against Breast Cancer in Mice,http://dx.doi.org/10.1371/journal.pone.0060190,PMC3618226,23577091,CC BY,"Legumain-based DNA vaccines have potential to protect against breast cancer. However, the lack of a safe and efficient oral delivery system restricts its clinical application. Here, we constructed alginic acid-coated chitosan nanoparticles (A.C.NPs) as an oral delivery carrier for a legumain DNA vaccine. First, we tested its characteristic in acidic environments in vitro. DNA agarose electrophoresis data show that A.C.NPs protected DNA better from degradation in acidic solution (pH 1.5) than did chitosan nanoparticles (C.NPs). Furthermore, size distribution analysis showed that A.C.NPs tended to aggregate and form micrometer scale complexes in pH<2.7, while dispersing into nanoparticles with an increase in pH. Mice were intragastrically administrated A.C.NPs carrying EGFP plasmids and EGFP expression was detected in the intestinal Peyer’s patches. Full-length legumain plasmids were loaded into different delivery carriers, including C.NPs, attenuated Salmonella typhimurium and A.C.NPs. A.C.NPs loaded with empty plasmids served as a control. Oral vaccination was performed in the murine orthotopic 4T1 breast cancer model. Our data indicate that tumor volume was significantly smaller in groups using A.C.NPs or attenuated Salmonella typhimurium as carriers. Furthermore, splenocytes co-cultured them with 4T1 cells pre-stimulated with CoCl(2), which influenced the translocation of legumain from cytoplasm to plasma membrane, showed a 4.7 and 2.3 folds increase in active cytotoxic T lymphocytes (CD3(+)/CD8(+)/CD25(+)) when treated with A.C.NPs carriers compared with PBS C.NPs. Our study suggests that C.NPs coated with alginic acid may be a safe and efficient tool for oral delivery of a DNA vaccine. Moreover, a legumain DNA vaccine delivered orally with A.C.NPs can effectively improve autoimmune response and protect against breast cancer in mice.",2013 Apr 5,"['Liu, Ze', 'Lv, Dan', 'Liu, Shu', 'Gong, Junbo', 'Wang, Da', 'Xiong, Min', 'Chen, Xiaoniao', 'Xiang, Rong', 'Tan, Xiaoyue']",PLoS One,,,True
c296f6a98b4eb94a69e4caef2df38ccf6e498511,PMC,Pathogenic mechanisms implicated in the intravascular coagulation in the lungs of BVDV-infected calves challenged with BHV-1,http://dx.doi.org/10.1186/1297-9716-44-20,PMC3618313,23506546,CC BY,"Resistance to respiratory disease in cattle requires host defense mechanisms that protect against pathogens which have evolved sophisticated strategies to evade them, including an altered function of pulmonary macrophages (MΦs) or the induction of inflammatory responses that cause lung injury and sepsis. The aim of this study was to clarify the mechanisms responsible for vascular changes occurring in the lungs of calves infected with bovine viral diarrhea virus (BVDV) and challenged later with bovine herpesvirus type 1 (BHV-1), evaluating the role of MΦs in the development of pathological lesions in this organ. For this purpose, pulmonary lesions were compared between co-infected calves and healthy animals inoculated only with BHV-1 through immunohistochemical (MAC387, TNFα, IL-1α, iNOS, COX-2 and Factor-VIII) and ultrastructural studies. Both groups of calves presented important vascular alterations produced by fibrin microthrombi and platelet aggregations within the blood vessels. These findings were earlier and more severe in the co-infected group, indicating that the concomitance of BVDV and BHV-1 in the lungs disrupts the pulmonary homeostasis by facilitating the establishment of an inflammatory and procoagulant environment modulated by inflammatory mediators released by pulmonary MΦs. In this regard, the co-infected calves, in spite of presenting a greater number of IMΦs than single-infected group, show a significant decrease in iNOS expression coinciding with the presence of more coagulation lesions. Moreover, animals pre-inoculated with BVDV displayed an alteration in the response of pro-inflammatory cytokines (TNFα and IL-1), which play a key role in activating the immune response, as well as in the local cell-mediated response.",2013 Mar 18,"['Risalde, María A', 'Molina, Verónica', 'Sánchez-Cordón, Pedro J', 'Romero-Palomo, Fernando', 'Pedrera, Miriam', 'Garfia, Bartolomé', 'Gómez-Villamandos, José C']",Vet Res,,,True
055ed1f10bcc96eacefe967b946a0b8c1674e197,PMC,Absence of CCR5 increases neutrophil recruitment in severe herpetic encephalitis,http://dx.doi.org/10.1186/1471-2202-14-19,PMC3618319,23391218,CC BY,"BACKGROUND: The neuroinflammatory response aimed at clearance of herpes simplex virus-1 (HSV-1) plays a key role in the pathogenesis of neuroaxonal damage in herpetic encephalitis. Leukocytes activated in an adaptive immune response access brain tissue by passing through the blood–brain barrier. The chemokine CCL5/RANTES is involved in recruitment of these cells to the brain acting via the receptors CCR1, CCR3 and mainly CCR5. Here, we evaluated the role of CCR5 on traffic of leukocytes in the brain microvasculature, cellular and cytokines profile in a severe form of herpetic encephalitis. RESULTS: Wild type and mice lacking CCR5 (CCR5(-/-)) were inoculated intracerebrally with 10(4) PFU of neurotropic HSV-1. We evaluated the traffic of leukocytes in the brain microvasculature using intravital microscopy and the profile of cytokines by Enzyme-Linked Immunosorbent Assay at 1 day post infection. Flow cytometry and histopathological analyses were also carried out in brain tissue. Absence of CCR5 leads to lower viral load and an increased leukocyte adhesion in brain microvasculature, predominantly of neutrophils (CD11(+) Ly6G(+) cells). Moreover, there was a significant increase in the levels of MIP-1/CCL2, RANTES/CCL5, KC/CXCL1 and MIG/CXCL9 in the brain of infected CCR5(-/-) mice. CONCLUSIONS: These results suggest that the absence of CCR5 may boost the immune response with a high neutrophil recruitment which most likely helps in viral clearance. Nonetheless, the elevated immune response may be detrimental to the host.",2013 Feb 7,"['Vilela, Márcia Carvalho', 'Lima, Graciela Kunrath', 'Rodrigues, David Henrique', 'Lacerda-Queiroz, Norinne', 'Pedroso, Vinicius Sousa Pietra', 'Miranda, Aline Silva', 'Rachid, Milene Alvarenga', 'Kroon, Erna Geessien', 'Campos, Marco Antônio', 'Teixeira, Mauro Martins', 'Sellner, Johann', 'Teixeira, Antonio Lucio']",BMC Neurosci,,,True
feaab7f92856f7b66f9e069f2686bc90660e9029,PMC,Multicomponent Therapeutics of Berberine Alkaloids,http://dx.doi.org/10.1155/2013/545898,PMC3619540,23634170,CC BY,"Although berberine alkaloids (BAs) are reported to be with broad-spectrum antibacterial and antiviral activities, the interactions among BAs have not been elucidated. In the present study, methicillin-resistant Staphylococcus aureus (MRSA) was chosen as a model organism, and modified broth microdilution was applied for the determination of the fluorescence absorption values to calculate the anti-MRSA activity of BAs. We have initiated four steps to seek the optimal combination of BAs that are (1) determining the anti-MRSA activity of single BA, (2) investigating the two-component combination to clarify the interactions among BAs by checkerboard assay, (3) investigating the multicomponent combination to determine the optimal ratio by quadratic rotation-orthogonal combination design, and (4) in vivo and in vitro validation of the optimal combination. The results showed that the interactions among BAs are related to their concentrations. The synergetic combinations included “berberine and epiberberine,” “jatrorrhizine and palmatine” and “jatrorrhizine and coptisine”; the antagonistic combinations included “coptisine and epiberberine”. The optimal combination was berberine : coptisine : jatrorrhizine : palmatine : epiberberine = 0.702 : 0.863 : 1 : 0.491 : 0.526, and the potency of the optimal combination on cyclophosphamide-immunocompromised mouse model was better than the natural combinations of herbs containing BAs.",2013 Mar 24,"['Luo, Jiaoyang', 'Yan, Dan', 'Yang, Meihua', 'Dong, Xiaoping', 'Xiao, Xiaohe']",Evid Based Complement Alternat Med,,,True
91781004fcf2142034de62e1212be3d885139060,PMC,"Using GPS Technology to Quantify Human Mobility, Dynamic Contacts and Infectious Disease Dynamics in a Resource-Poor Urban Environment",http://dx.doi.org/10.1371/journal.pone.0058802,PMC3620113,23577059,CC BY,"Empiric quantification of human mobility patterns is paramount for better urban planning, understanding social network structure and responding to infectious disease threats, especially in light of rapid growth in urbanization and globalization. This need is of particular relevance for developing countries, since they host the majority of the global urban population and are disproportionally affected by the burden of disease. We used Global Positioning System (GPS) data-loggers to track the fine-scale (within city) mobility patterns of 582 residents from two neighborhoods from the city of Iquitos, Peru. We used ∼2.3 million GPS data-points to quantify age-specific mobility parameters and dynamic co-location networks among all tracked individuals. Geographic space significantly affected human mobility, giving rise to highly local mobility kernels. Most (∼80%) movements occurred within 1 km of an individual’s home. Potential hourly contacts among individuals were highly irregular and temporally unstructured. Only up to 38% of the tracked participants showed a regular and predictable mobility routine, a sharp contrast to the situation in the developed world. As a case study, we quantified the impact of spatially and temporally unstructured routines on the dynamics of transmission of an influenza-like pathogen within an Iquitos neighborhood. Temporally unstructured daily routines (e.g., not dominated by a single location, such as a workplace, where an individual repeatedly spent significant amount of time) increased an epidemic’s final size and effective reproduction number by 20% in comparison to scenarios modeling temporally structured contacts. Our findings provide a mechanistic description of the basic rules that shape human mobility within a resource-poor urban center, and contribute to the understanding of the role of fine-scale patterns of individual movement and co-location in infectious disease dynamics. More generally, this study emphasizes the need for careful consideration of human social interactions when designing infectious disease mitigation strategies, particularly within resource-poor urban environments.",2013 Apr 8,"['Vazquez-Prokopec, Gonzalo M.', 'Bisanzio, Donal', 'Stoddard, Steven T.', 'Paz-Soldan, Valerie', 'Morrison, Amy C.', 'Elder, John P.', 'Ramirez-Paredes, Jhon', 'Halsey, Eric S.', 'Kochel, Tadeusz J.', 'Scott, Thomas W.', 'Kitron, Uriel']",PLoS One,,,True
7cd5321d8b9deb046502c0f1ab1581e7200bc378,PMC,DNA Vaccine Delivered by a Needle-Free Injection Device Improves Potency of Priming for Antibody and CD8+ T-Cell Responses after rAd5 Boost in a Randomized Clinical Trial,http://dx.doi.org/10.1371/journal.pone.0059340,PMC3620125,23577062,CC0,"BACKGROUND: DNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO(2)-powered Biojector® device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity. METHODS: Forty adults, 18–50 years, were randomly assigned to intramuscular (IM) vaccinations with DNA vaccine, VRC-HIVDNA016-00-VP, (weeks 0, 4, 8) by Biojector® 2000™ or needle and syringe (N/S) and boosted IM at week 24 with VRC-HIVADV014-00-VP (rAd5) with N/S at 10(10) or 10(11) particle units (PU). Equal numbers per assigned schedule had low (≤500) or high (>500) reciprocal titers of preexisting Ad5 neutralizing antibody. RESULTS: 120 DNA and 39 rAd5 injections were given; 36 subjects completed follow-up research sample collections. IFN-γ ELISpot response rates were 17/19 (89%) for Biojector® and 13/17 (76%) for N/S delivery at Week 28 (4 weeks post rAd5 boost). The magnitude of ELISpot response was about 3-fold higher in Biojector® compared to N/S groups. Similar effects on response rates and magnitude were observed for CD8+, but not CD4+ T-cell responses by ICS. Env-specific antibody responses were about 10-fold higher in Biojector-primed subjects. CONCLUSIONS: DNA vaccination by Biojector® was well-tolerated and compared to needle injection, primed for greater IFN-γ ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting. TRIAL REGISTRATION: ClinicalTrials.gov NCT00109629",2013 Apr 8,"['Graham, Barney S.', 'Enama, Mary E.', 'Nason, Martha C.', 'Gordon, Ingelise J.', 'Peel, Sheila A.', 'Ledgerwood, Julie E.', 'Plummer, Sarah A.', 'Mascola, John R.', 'Bailer, Robert T.', 'Roederer, Mario', 'Koup, Richard A.', 'Nabel, Gary J.', None]",PLoS One,,,True
a2f53651474ffa6ede94371fa2d2e735395d965e,PMC,DNA Vaccine Delivered by a Needle-Free Injection Device Improves Potency of Priming for Antibody and CD8+ T-Cell Responses after rAd5 Boost in a Randomized Clinical Trial,http://dx.doi.org/10.1371/journal.pone.0059340,PMC3620125,23577062,CC0,"BACKGROUND: DNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO(2)-powered Biojector® device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity. METHODS: Forty adults, 18–50 years, were randomly assigned to intramuscular (IM) vaccinations with DNA vaccine, VRC-HIVDNA016-00-VP, (weeks 0, 4, 8) by Biojector® 2000™ or needle and syringe (N/S) and boosted IM at week 24 with VRC-HIVADV014-00-VP (rAd5) with N/S at 10(10) or 10(11) particle units (PU). Equal numbers per assigned schedule had low (≤500) or high (>500) reciprocal titers of preexisting Ad5 neutralizing antibody. RESULTS: 120 DNA and 39 rAd5 injections were given; 36 subjects completed follow-up research sample collections. IFN-γ ELISpot response rates were 17/19 (89%) for Biojector® and 13/17 (76%) for N/S delivery at Week 28 (4 weeks post rAd5 boost). The magnitude of ELISpot response was about 3-fold higher in Biojector® compared to N/S groups. Similar effects on response rates and magnitude were observed for CD8+, but not CD4+ T-cell responses by ICS. Env-specific antibody responses were about 10-fold higher in Biojector-primed subjects. CONCLUSIONS: DNA vaccination by Biojector® was well-tolerated and compared to needle injection, primed for greater IFN-γ ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting. TRIAL REGISTRATION: ClinicalTrials.gov NCT00109629",2013 Apr 8,"['Graham, Barney S.', 'Enama, Mary E.', 'Nason, Martha C.', 'Gordon, Ingelise J.', 'Peel, Sheila A.', 'Ledgerwood, Julie E.', 'Plummer, Sarah A.', 'Mascola, John R.', 'Bailer, Robert T.', 'Roederer, Mario', 'Koup, Richard A.', 'Nabel, Gary J.', None]",PLoS One,,,True
ca0cc9c9da1307a7f36276eea4d117d6f74c2d7f,PMC,Attenuation of Mouse Hepatitis Virus by Deletion of the LLRKxGxKG Region of Nsp1,http://dx.doi.org/10.1371/journal.pone.0061166,PMC3620170,23593419,CC BY,"Coronaviruses are a family of large positive-sense RNA viruses that are responsible for a wide range of important veterinary and human diseases. Nsp1 has been shown to have an important role in the pathogenetic mechanisms of coronaviruses in vivo. To assess the function of a relatively conserved domain (LLRKxGxKG) of MHV nsp1, a mutant virus, MHV-nsp1-27D, with a 27 nts (LLRKxGxKG) deletion in nsp1, was constructed using a reverse genetic system with a vaccinia virus vector. The mutant virus had similar growth kinetics to MHV-A59 wild-type virus in 17CI-1 cells, but was highly attenuated in vivo. Moreover, the mutant virus completely protected C57BL/6 mice from a lethal MHV-A59 challenge. To further analyze the mechanism of the attenuation of the mutant virus, changes in reporter gene expression were measured in nsp1- or nsp1-27D-expressing cells; the results showed that nsp1 inhibited reporter gene expression controlled by different promoters, but that this inhibition was reduced for nsp1-27D. The research in vivo and in vitro suggests that the LLRKxGxKG region of nsp1 may play an important role in this process.",2013 Apr 8,"['Lei, Lin', 'Ying, Sun', 'Baojun, Luo', 'Yi, Yang', 'Xiang, He', 'Wenli, Su', 'Zounan, Sun', 'Deyin, Guo', 'Qingyu, Zhu', 'Jingmei, Liu', 'Guohui, Chang']",PLoS One,,,True
6b810552f81fc62a9f69f64033011fd5c627c8ea,PMC,Identification of diverse full-length endogenous betaretroviruses in megabats and microbats,http://dx.doi.org/10.1186/1742-4690-10-35,PMC3621094,23537098,CC BY,"BACKGROUND: Betaretroviruses infect a wide range of species including primates, rodents, ruminants, and marsupials. They exist in both endogenous and exogenous forms and are implicated in animal diseases such as lung cancer in sheep, and in human disease, with members of the human endogenous retrovirus-K (HERV-K) group of endogenous betaretroviruses (βERVs) associated with human cancers and autoimmune diseases. To improve our understanding of betaretroviruses in an evolutionarily distinct host species, we characterized βERVs present in the genomes and transcriptomes of mega- and microbats, which are an important reservoir of emerging viruses. RESULTS: A diverse range of full-length βERVs were discovered in mega- and microbat genomes and transcriptomes including the first identified intact endogenous retrovirus in a bat. Our analysis revealed that the genus Betaretrovirus can be divided into eight distinct sub-groups with evidence of cross-species transmission. Betaretroviruses are revealed to be a complex retrovirus group, within which one sub-group has evolved from complex to simple genomic organization through the acquisition of an env gene from the genus Gammaretrovirus. Molecular dating suggests that bats have contended with betaretroviral infections for over 30 million years. CONCLUSIONS: Our study reveals that a diverse range of betaretroviruses have circulated in bats for most of their evolutionary history, and cluster with extant betaretroviruses of divergent mammalian lineages suggesting that their distribution may be largely unrestricted by host species barriers. The presence of βERVs with the ability to transcribe active viral elements in a major animal reservoir for viral pathogens has potential implications for public health.",2013 Mar 27,"['Hayward, Joshua A', 'Tachedjian, Mary', 'Cui, Jie', 'Field, Hume', 'Holmes, Edward C', 'Wang, Lin-Fa', 'Tachedjian, Gilda']",Retrovirology,,,True
f50e4c99f7dcf23d79095c8d45048edf342e8db4,PMC,Identification of diverse full-length endogenous betaretroviruses in megabats and microbats,http://dx.doi.org/10.1186/1742-4690-10-35,PMC3621094,23537098,CC BY,"BACKGROUND: Betaretroviruses infect a wide range of species including primates, rodents, ruminants, and marsupials. They exist in both endogenous and exogenous forms and are implicated in animal diseases such as lung cancer in sheep, and in human disease, with members of the human endogenous retrovirus-K (HERV-K) group of endogenous betaretroviruses (βERVs) associated with human cancers and autoimmune diseases. To improve our understanding of betaretroviruses in an evolutionarily distinct host species, we characterized βERVs present in the genomes and transcriptomes of mega- and microbats, which are an important reservoir of emerging viruses. RESULTS: A diverse range of full-length βERVs were discovered in mega- and microbat genomes and transcriptomes including the first identified intact endogenous retrovirus in a bat. Our analysis revealed that the genus Betaretrovirus can be divided into eight distinct sub-groups with evidence of cross-species transmission. Betaretroviruses are revealed to be a complex retrovirus group, within which one sub-group has evolved from complex to simple genomic organization through the acquisition of an env gene from the genus Gammaretrovirus. Molecular dating suggests that bats have contended with betaretroviral infections for over 30 million years. CONCLUSIONS: Our study reveals that a diverse range of betaretroviruses have circulated in bats for most of their evolutionary history, and cluster with extant betaretroviruses of divergent mammalian lineages suggesting that their distribution may be largely unrestricted by host species barriers. The presence of βERVs with the ability to transcribe active viral elements in a major animal reservoir for viral pathogens has potential implications for public health.",2013 Mar 27,"['Hayward, Joshua A', 'Tachedjian, Mary', 'Cui, Jie', 'Field, Hume', 'Holmes, Edward C', 'Wang, Lin-Fa', 'Tachedjian, Gilda']",Retrovirology,,,False
cc74f79668feafbc452602e7de4304aec2d411b6,PMC,Identification of diverse full-length endogenous betaretroviruses in megabats and microbats,http://dx.doi.org/10.1186/1742-4690-10-35,PMC3621094,23537098,CC BY,"BACKGROUND: Betaretroviruses infect a wide range of species including primates, rodents, ruminants, and marsupials. They exist in both endogenous and exogenous forms and are implicated in animal diseases such as lung cancer in sheep, and in human disease, with members of the human endogenous retrovirus-K (HERV-K) group of endogenous betaretroviruses (βERVs) associated with human cancers and autoimmune diseases. To improve our understanding of betaretroviruses in an evolutionarily distinct host species, we characterized βERVs present in the genomes and transcriptomes of mega- and microbats, which are an important reservoir of emerging viruses. RESULTS: A diverse range of full-length βERVs were discovered in mega- and microbat genomes and transcriptomes including the first identified intact endogenous retrovirus in a bat. Our analysis revealed that the genus Betaretrovirus can be divided into eight distinct sub-groups with evidence of cross-species transmission. Betaretroviruses are revealed to be a complex retrovirus group, within which one sub-group has evolved from complex to simple genomic organization through the acquisition of an env gene from the genus Gammaretrovirus. Molecular dating suggests that bats have contended with betaretroviral infections for over 30 million years. CONCLUSIONS: Our study reveals that a diverse range of betaretroviruses have circulated in bats for most of their evolutionary history, and cluster with extant betaretroviruses of divergent mammalian lineages suggesting that their distribution may be largely unrestricted by host species barriers. The presence of βERVs with the ability to transcribe active viral elements in a major animal reservoir for viral pathogens has potential implications for public health.",2013 Mar 27,"['Hayward, Joshua A', 'Tachedjian, Mary', 'Cui, Jie', 'Field, Hume', 'Holmes, Edward C', 'Wang, Lin-Fa', 'Tachedjian, Gilda']",Retrovirology,,,False
928c0266f9fede929216a7c6f3370d32ff638401,PMC,Virological and clinical characterizations of respiratory infections in hospitalized children,http://dx.doi.org/10.1186/1824-7288-39-22,PMC3621398,23536956,CC BY,"BACKGROUND: The purpose of this study was to determine the incidence and seasonal distribution of viral etiological agents and to compare their clinical manifestations and disease severity, including single and co infections. METHODS: Multiplex reverse-transcription PCR was performed for the detection of viruses in nasopharyngeal aspirat. Disease severity was grouped using a categorization index as very mild/mild, and moderate/severe. Clinical and laboratory characteristics of hospitalized children with viral respiratory tract infection were analyzed. RESULTS: Viral pathogens were detected in 103/155 (66.5%) of patients. In order of frequency, identified pathogens were respiratory syncytial virus (32.0%), adenovirus (26.2%), parainfluenza viruses type 1–4 (19.4%), rhinovirus (18.4%), influenza A and B (12.6%), human metapneumovirus (12.6%), coronavirus (2.9%), and bocavirus (0.9%). Coinfections were present in 21 samples. Most of the children had very mild (38.8%) and mild disease (37.9%). Severity of illness was not worse with coinfections. The most common discharge diagnoses were ""URTI"" with or without LRTI/asthma (n=58). Most viruses exhibited strong seasonal patterns. Leukocytosis (22.2%) and neutrophilia (36.6%) were most commonly detected in patients with adenovirus and rhinovirus (p<0.05). Monocytosis was the most remarkable finding in the patients (n=48, 53.3%), especially in patients with adenovirus (p<0.05). CONCLUSIONS: RSV and RhV were associated with higher severity of illness in hospitalized children. RSV found to account for half of LRTI hospitalizations. In AdV and FluA and B infections, fever lasted longer than in other viruses. Coinfections were detected in 21 of the patients. The presence of coinfections was not associated with increased disease severity.",2013 Mar 27,"['Bicer, Suat', 'Giray, Tuba', 'Çöl, Defne', 'Erdağ, Gülay Çiler', 'Vitrinel, Ayça', 'Gürol, Yesim', 'Çelik, Gülden', 'Kaspar, Çigdem', 'Küçük, Öznur']",Ital J Pediatr,,,True
cd06185d94b38abd3c8209a45897a589da964bf2,PMC,De novo Sequence Assembly and Characterization of Lycoris aurea Transcriptome Using GS FLX Titanium Platform of 454 Pyrosequencing,http://dx.doi.org/10.1371/journal.pone.0060449,PMC3621892,23593220,CC BY,"BACKGROUND: Lycoris aurea, also called Golden Magic Lily, is an ornamentally and medicinally important species of the Amaryllidaceae family. To date, the sequencing of its whole genome is unavailable as a non-model organism. Transcriptomic information is also scarce for this species. In this study, we performed de novo transcriptome sequencing to produce the first comprehensive expressed sequence tag (EST) dataset for L. aurea using high-throughput sequencing technology. METHODOLOGY AND PRINCIPAL FINDINGS: Total RNA was isolated from leaves with sodium nitroprusside (SNP), salicylic acid (SA), or methyl jasmonate (MeJA) treatment, stems, and flowers at the bud, blooming, and wilting stages. Equal quantities of RNA from each tissue and stage were pooled to construct a cDNA library. Using 454 pyrosequencing technology, a total of 937,990 high quality reads (308.63 Mb) with an average read length of 329 bp were generated. Clustering and assembly of these reads produced a non-redundant set of 141,111 unique sequences, comprising 24,604 contigs and 116,507 singletons. All of the unique sequences were involved in the biological process, cellular component and molecular function categories by GO analysis. Potential genes and their functions were predicted by KEGG pathway mapping and COG analysis. Based on our sequence analysis and published literatures, many putative genes involved in Amaryllidaceae alkaloids synthesis, including PAL, TYDC OMT, NMT, P450, and other potentially important candidate genes, were identified for the first time in this Lycoris. Furthermore, 6,386 SSRs and 18,107 high-confidence SNPs were identified in this EST dataset. CONCLUSIONS: The transcriptome provides an invaluable new data for a functional genomics resource and future biological research in L. aurea. The molecular markers identified in this study will provide a material basis for future genetic linkage and quantitative trait loci analyses, and will provide useful information for functional genomic research in future.",2013 Apr 9,"['Wang, Ren', 'Xu, Sheng', 'Jiang, Yumei', 'Jiang, Jingwei', 'Li, Xiaodan', 'Liang, Lijian', 'He, Jia', 'Peng, Feng', 'Xia, Bing']",PLoS One,,,True
a21f16327c9af00dfc25321123ac2a5b6eb7f690,PMC,Clinical Characteristics and Outcomes in Hospitalized Patients with Respiratory Viral Co-Infection during the 2009 H1N1 Influenza Pandemic,http://dx.doi.org/10.1371/journal.pone.0060845,PMC3622008,23585856,CC BY,"BACKGROUND: The clinical consequences of co-infection with two or more respiratory viruses are poorly understood. We sought to determine if co-infection with pandemic 2009–2010 influenza A H1N1 (pH1N1) and another respiratory virus was associated with worse clinical outcomes. METHODS: A retrospective cohort study was performed of all hospitalized patients with a positive respiratory viral panel (RVP) for two or more viruses within 72 hours of admission at our institution from October 2009 to December 2009. We compared patients infected with one respiratory virus to those with respiratory viral co-infection. RESULTS: We identified 617 inpatients with a positive RVP sample with a single virus and 49 inpatients with a positive RVP sample for two viruses (i.e. co-infection). Co-infected patients were significantly younger, more often had fever/chills, tachypnea, and they more often demonstrated interstitial opacities suggestive of viral pneumonia on the presenting chest radiograph (OR 7.5, 95% CI 3.4–16.5). The likelihood of death, length of stay, and requirement for intensive care unit level of care were similar in both groups, but patients with any respiratory virus co-infection were more likely to experience complications, particularly treatment for a secondary bacterial pneumonia (OR 6.8, 95% CI 3.3–14.2). Patients co-infected with pH1N1 and another respiratory virus were more likely to present with chest radiograph changes suggestive of a viral pneumonia, compared to mono-infection with pH1N1 (OR 16.9, 95% CI 4.5–62.7). By logistic regression using mono-infection with non-PH1N1 viruses as the reference group, co-infection with pH1N1 was the strongest independent predictor of treatment for a secondary bacterial pneumonia (OR 17.8, 95% CI 6.7–47.1). CONCLUSION: Patients with viral co-infection, particularly with pH1N1, were more likely to have chest radiograph features compatible with a viral pneumonia and complications during their hospital course, particularly treatment for secondary bacterial pneumonia. Despite this, co-infection was not associated with ICU admission.",2013 Apr 9,"['Echenique, Ignacio A.', 'Chan, Philip A.', 'Chapin, Kimberle C.', 'Andrea, Sarah B.', 'Fava, Joseph L.', 'Mermel, Leonard A.']",PLoS One,,,True
ec9ad2ac0be589d617f25f1cfc349f644d1bebf1,PMC,Intrahost Diversity of Feline Coronavirus: A Consensus between the Circulating Virulent/Avirulent Strains and the Internal Mutation Hypotheses?,http://dx.doi.org/10.1155/2013/572325,PMC3622387,23589704,CC BY,"To evaluate the most controversial issue concerning current feline coronavirus (FCoV) virology, the coexisting hypotheses of the intrahost and interhost origins of feline infectious peritonitis virus (FIPV) in regard to the pathogenesis of feline infectious peritonitis (FIP), this study aimed to assess the molecular diversity of the membrane gene FCoVs in 190 samples from 10 cats with signs of FIP and in 5 faecal samples from cats without signs of FIP. All samples from the non-FIP cats and 25.26% of the samples from the FIP cats were positive for the FCoV membrane (M) gene. Mutations in this gene consisted of SNP changes randomly scattered among the sequences; few mutations resulted in amino acid changes. No geographic pattern was observed. Of the cats without FIP that harboured FECoV, the amino acid sequence identities for the M gene were 100% among cats (Cats 1–3) from the same cattery, and the overall sequence identity for the M gene was ≥91%. In one cat, two different lineages of FCoV, one enteric and one systemic, were found that segregated apart in the M gene tree. In conclusion, the in vivo mutation transition hypothesis and the circulating high virulent-low virulent FCoV hypothesis have been found to be plausible according to the results obtained from sequencing the M gene.",2013 Mar 27,"['Hora, Aline S.', 'Asano, Karen M.', 'Guerra, Juliana M.', 'Mesquita, Ramon G.', 'Maiorka, Paulo', 'Richtzenhain, Leonardo J.', 'Brandão, Paulo E.']",ScientificWorldJournal,,,True
825bf8562f3e44a02f8f2bcbf055586d42771f0a,PMC,The closterovirus-derived gene expression and RNA interference vectors as tools for research and plant biotechnology,http://dx.doi.org/10.3389/fmicb.2013.00083,PMC3622897,23596441,CC BY,"Important progress in understanding replication, interactions with host plants, and evolution of closteroviruses enabled engineering of several vectors for gene expression and virus-induced gene silencing. Due to the broad host range of closteroviruses, these vectors expanded vector applicability to include important woody plants such as citrus and grapevine. Furthermore, large closterovirus genomes offer genetic capacity and stability unrivaled by other plant viral vectors. These features provided immense opportunities for using closterovirus vectors for the functional genomics studies and pathogen control in economically valuable crops. This review briefly summarizes advances in closterovirus research during the last decade, explores the relationships between virus biology and vector design, and outlines the most promising directions for future application of closterovirus vectors.",2013 Apr 11,"['Dolja, Valerian V.', 'Koonin, Eugene V.']",Front Microbiol,,,True
d07d6b58460992a4530b7b24d66e8b3861036a50,PMC,Host Cell Entry of Respiratory Syncytial Virus Involves Macropinocytosis Followed by Proteolytic Activation of the F Protein,http://dx.doi.org/10.1371/journal.ppat.1003309,PMC3623752,23593008,CC BY,"Respiratory Syncytial Virus (RSV) is a highly pathogenic member of the Paramyxoviridae that causes severe respiratory tract infections. Reports in the literature have indicated that to infect cells the incoming viruses either fuse their envelope directly with the plasma membrane or exploit clathrin-mediated endocytosis. To study the entry process in human tissue culture cells (HeLa, A549), we used fluorescence microscopy and developed quantitative, FACS-based assays to follow virus binding to cells, endocytosis, intracellular trafficking, membrane fusion, and infection. A variety of perturbants were employed to characterize the cellular processes involved. We found that immediately after binding to cells RSV activated a signaling cascade involving the EGF receptor, Cdc42, PAK1, and downstream effectors. This led to a series of dramatic actin rearrangements; the cells rounded up, plasma membrane blebs were formed, and there was a significant increase in fluid uptake. If these effects were inhibited using compounds targeting Na(+)/H(+) exchangers, myosin II, PAK1, and other factors, no infection was observed. The RSV was rapidly and efficiently internalized by an actin-dependent process that had all hallmarks of macropinocytosis. Rather than fusing with the plasma membrane, the viruses thus entered Rab5-positive, fluid-filled macropinosomes, and fused with the membranes of these on the average 50 min after internalization. Rab5 was required for infection. To find an explanation for the endocytosis requirement, which is unusual among paramyxoviruses, we analyzed the fusion protein, F, and could show that, although already cleaved by a furin family protease once, it underwent a second, critical proteolytic cleavage after internalization. This cleavage by a furin-like protease removed a small peptide from the F1 subunits, and made the virus infectious.",2013 Apr 11,"['Krzyzaniak, Magdalena Anna', 'Zumstein, Michael Thomas', 'Gerez, Juan Atilio', 'Picotti, Paola', 'Helenius, Ari']",PLoS Pathog,,,True
94156e6941fe78191b5997cdeb10cb3fd06e1221,PMC,"Complete genome sequence of acute viral necrosis virus associated with massive mortality outbreaks in the Chinese scallop, Chlamys farreri",http://dx.doi.org/10.1186/1743-422X-10-110,PMC3623871,23566284,CC BY,"BACKGROUND: Acute viral necrosis virus (AVNV) is the causative agent of a serious disease resulting in high mortality in cultured Chinese scallops, Chlamys farreri. We have sequenced and analyzed the complete genome of AVNV. RESULTS: The AVNV genome is a linear, double-stranded DNA molecule of 210,993 bp with a nucleotide composition of 38.5% G + C. A total of 123 open reading frames were predicted to encode functional proteins, ranging from 41 to 1,878 amino acid residues. The DNA sequence of AVNV is 97% identical to that of ostreid herpesvirus 1 (OsHV-1), and the amino acid sequences of the encoded proteins of these two viruses are 94-100% identical. The genomic organization of AVNV is similar to that of OsHV-1, and consists of two unique regions (170.4 kb and 3.4 kb, respectively), each flanked by two inverted repeats (7.6 kb and 10.2 kb, respectively), with a third unique region (1.5 kb) situated between the two internal repeats. CONCLUSIONS: Our results indicate that AVNV is a variant of OsHV-1. The AVNV genome sequence provides information useful for understanding the evolution and divergence of OsHV-1 in marine molluscs.",2013 Apr 8,"['Ren, Weicheng', 'Chen, Haixia', 'Renault, Tristan', 'Cai, Yuyong', 'Bai, Changming', 'Wang, Chongming', 'Huang, Jie']",Virol J,,,True
cd18b402ae6cf0913a3a12aef3a8819964d8057e,PMC,Pig immune response to general stimulus and to porcine reproductive and respiratory syndrome virus infection: a meta-analysis approach,http://dx.doi.org/10.1186/1471-2164-14-220,PMC3623894,23552196,CC BY,"BACKGROUND: The availability of gene expression data that corresponds to pig immune response challenges provides compelling material for the understanding of the host immune system. Meta-analysis offers the opportunity to confirm and expand our knowledge by combining and studying at one time a vast set of independent studies creating large datasets with increased statistical power. In this study, we performed two meta-analyses of porcine transcriptomic data: i) scrutinized the global immune response to different challenges, and ii) determined the specific response to Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection. To gain an in-depth knowledge of the pig response to PRRSV infection, we used an original approach comparing and eliminating the common genes from both meta-analyses in order to identify genes and pathways specifically involved in the PRRSV immune response. The software Pointillist was used to cope with the highly disparate data, circumventing the biases generated by the specific responses linked to single studies. Next, we used the Ingenuity Pathways Analysis (IPA) software to survey the canonical pathways, biological functions and transcription factors found to be significantly involved in the pig immune response. We used 779 chips corresponding to 29 datasets for the pig global immune response and 279 chips obtained from 6 datasets for the pig response to PRRSV infection, respectively. RESULTS: The pig global immune response analysis showed interconnected canonical pathways involved in the regulation of translation and mitochondrial energy metabolism. Biological functions revealed in this meta-analysis were centred around translation regulation, which included protein synthesis, RNA-post transcriptional gene expression and cellular growth and proliferation. Furthermore, the oxidative phosphorylation and mitochondria dysfunctions, associated with stress signalling, were highly regulated. Transcription factors such as MYCN, MYC and NFE2L2 were found in this analysis to be potentially involved in the regulation of the immune response. The host specific response to PRRSV infection engendered the activation of well-defined canonical pathways in response to pathogen challenge such as TREM1, toll-like receptor and hyper-cytokinemia/ hyper-chemokinemia signalling. Furthermore, this analysis brought forth the central role of the crosstalk between innate and adaptive immune response and the regulation of anti-inflammatory response. The most significant transcription factor potentially involved in this analysis was HMGB1, which is required for the innate recognition of viral nucleic acids. Other transcription factors like interferon regulatory factors IRF1, IRF3, IRF5 and IRF8 were also involved in the pig specific response to PRRSV infection. CONCLUSIONS: This work reveals key genes, canonical pathways and biological functions involved in the pig global immune response to diverse challenges, including PRRSV infection. The powerful statistical approach led us to consolidate previous findings as well as to gain new insights into the pig immune response either to common stimuli or specifically to PRRSV infection.",2013 Apr 3,"['Badaoui, Bouabid', 'Tuggle, Christopher K', 'Hu, Zhiliang', 'Reecy, James M', 'Ait-Ali, Tahar', 'Anselmo, Anna', 'Botti, Sara']",BMC Genomics,,,True
75f36f193e2cbaa2f34b23bfc645dd441551bd51,PMC,The Impact of Model Building on the Transmission Dynamics under Vaccination: Observable (Symptom-Based) versus Unobservable (Contagiousness-Dependent) Approaches,http://dx.doi.org/10.1371/journal.pone.0062062,PMC3625221,23593507,CC BY,"BACKGROUND: The way we formulate a mathematical model of an infectious disease to capture symptomatic and asymptomatic transmission can greatly influence the likely effectiveness of vaccination in the presence of vaccine effect for preventing clinical illness. The present study aims to assess the impact of model building strategy on the epidemic threshold under vaccination. METHODOLOGY/PRINCIPAL FINDINGS: We consider two different types of mathematical models, one based on observable variables including symptom onset and recovery from clinical illness (hereafter, the “observable model”) and the other based on unobservable information of infection event and infectiousness (the “unobservable model”). By imposing a number of modifying assumptions to the observable model, we let it mimic the unobservable model, identifying that the two models are fully consistent only when the incubation period is identical to the latent period and when there is no pre-symptomatic transmission. We also computed the reproduction numbers with and without vaccination, demonstrating that the data generating process of vaccine-induced reduction in symptomatic illness is consistent with the observable model only and examining how the effective reproduction number is differently calculated by two models. CONCLUSIONS: To explicitly incorporate the vaccine effect in reducing the risk of symptomatic illness into the model, it is fruitful to employ a model that directly accounts for disease progression. More modeling studies based on observable epidemiological information are called for.",2013 Apr 12,"['Ejima, Keisuke', 'Aihara, Kazuyuki', 'Nishiura, Hiroshi']",PLoS One,,,True
145bb000d606bc2ea82e7e11f79363796bc9b7b1,PMC,Widespread Divergence of the CEACAM/PSG Genes in Vertebrates and Humans Suggests Sensitivity to Selection,http://dx.doi.org/10.1371/journal.pone.0061701,PMC3628338,23613906,CC BY,"In mammals, carcinoembryonic antigen cell adhesion molecules (CEACAMs) and pregnancy-specific glycoproteins (PSGs) play important roles in the regulation of pathogen transmission, tumorigenesis, insulin signaling turnover, and fetal–maternal interactions. However, how these genes evolved and to what extent they diverged in humans remain to be investigated specifically. Based on syntenic mapping of chordate genomes, we reveal that diverging homologs with a prototypic CEACAM architecture–including an extracellular domain with immunoglobulin variable and constant domain-like regions, and an intracellular domain containing ITAM motif–are present from cartilaginous fish to humans, but are absent in sea lamprey, cephalochordate or urochordate. Interestingly, the CEACAM/PSG gene inventory underwent radical divergence in various vertebrate lineages: from zero in avian species to dozens in therian mammals. In addition, analyses of genetic variations in human populations showed the presence of various types of copy number variations (CNVs) at the CEACAM/PSG locus. These copy number polymorphisms have 3–80% frequency in select populations, and encompass single to more than six PSG genes. Furthermore, we found that CEACAM/PSG genes contain a significantly higher density of nonsynonymous single nucleotide polymorphism (SNP) compared to the chromosome average, and many CEACAM/PSG SNPs exhibit high population differentiation. Taken together, our study suggested that CEACAM/PSG genes have had a more dynamic evolutionary history in vertebrates than previously thought. Given that CEACAM/PSGs play important roles in maternal–fetal interaction and pathogen recognition, these data have laid the groundwork for future analysis of adaptive CEACAM/PSG genotype-phenotypic relationships in normal and complicated pregnancies as well as other etiologies.",2013 Apr 16,"['Chang, Chia Lin', 'Semyonov, Jenia', 'Cheng, Po Jen', 'Huang, Shang Yu', 'Park, Jae Il', 'Tsai, Huai-Jen', 'Lin, Cheng-Yung', 'Grützner, Frank', 'Soong, Yung Kuei', 'Cai, James J.', 'Hsu, Sheau Yu Teddy']",PLoS One,,,True
a977a48fcb972ec87cd97bd7017fd08c1d3d9ca2,PMC,Widespread Divergence of the CEACAM/PSG Genes in Vertebrates and Humans Suggests Sensitivity to Selection,http://dx.doi.org/10.1371/journal.pone.0061701,PMC3628338,23613906,CC BY,"In mammals, carcinoembryonic antigen cell adhesion molecules (CEACAMs) and pregnancy-specific glycoproteins (PSGs) play important roles in the regulation of pathogen transmission, tumorigenesis, insulin signaling turnover, and fetal–maternal interactions. However, how these genes evolved and to what extent they diverged in humans remain to be investigated specifically. Based on syntenic mapping of chordate genomes, we reveal that diverging homologs with a prototypic CEACAM architecture–including an extracellular domain with immunoglobulin variable and constant domain-like regions, and an intracellular domain containing ITAM motif–are present from cartilaginous fish to humans, but are absent in sea lamprey, cephalochordate or urochordate. Interestingly, the CEACAM/PSG gene inventory underwent radical divergence in various vertebrate lineages: from zero in avian species to dozens in therian mammals. In addition, analyses of genetic variations in human populations showed the presence of various types of copy number variations (CNVs) at the CEACAM/PSG locus. These copy number polymorphisms have 3–80% frequency in select populations, and encompass single to more than six PSG genes. Furthermore, we found that CEACAM/PSG genes contain a significantly higher density of nonsynonymous single nucleotide polymorphism (SNP) compared to the chromosome average, and many CEACAM/PSG SNPs exhibit high population differentiation. Taken together, our study suggested that CEACAM/PSG genes have had a more dynamic evolutionary history in vertebrates than previously thought. Given that CEACAM/PSGs play important roles in maternal–fetal interaction and pathogen recognition, these data have laid the groundwork for future analysis of adaptive CEACAM/PSG genotype-phenotypic relationships in normal and complicated pregnancies as well as other etiologies.",2013 Apr 16,"['Chang, Chia Lin', 'Semyonov, Jenia', 'Cheng, Po Jen', 'Huang, Shang Yu', 'Park, Jae Il', 'Tsai, Huai-Jen', 'Lin, Cheng-Yung', 'Grützner, Frank', 'Soong, Yung Kuei', 'Cai, James J.', 'Hsu, Sheau Yu Teddy']",PLoS One,,,False
44f9f629bf4db860b1cbb1cce7f925d0f7d29b30,PMC,Regulation of the Epithelial Adhesion Molecule CEACAM1 Is Important for Palate Formation,http://dx.doi.org/10.1371/journal.pone.0061653,PMC3629100,23613893,CC BY,"Cleft palate results from a mixture of genetic and environmental factors and occurs when the bilateral palatal shelves fail to fuse. The objective of this study was to search for new genes involved in mouse palate formation. Gene expression of murine embryonic palatal tissue was analyzed at various developmental stages before, during, and after palate fusion using GeneChip® microarrays. Ceacam1 was one of the highly up-regulated genes during palate formation, and this was confirmed by quantitative real-time PCR. Immunohistochemical staining showed that CEACAM1 was present in prefusion palatal epithelium and was degraded during fusion. To investigate the developmental role of CEACAM1, function-blocking antibody was added to embryonic mouse palate in organ culture. Palatal fusion was inhibited by this function-blocking antibody. To investigate the subsequent developmental role of CEACAM1, we characterized Ceacam1-deficient (Ceacam1 (−/−)) mice. Epithelial cells persisted abnormally at the midline of the embryonic palate even on day E16.0, and palatal fusion was delayed in Ceacam1 (−/−) mice. TGFβ3 expression, apoptosis, and cell proliferation in palatal epithelium were not affected in the palate of Ceacam1(−/−)mice. However, CEACAM1 expression was retained in the remaining MEE of TGFβ-deficient mice. These results suggest that CEACAM1 has roles in the initiation of palatal fusion via epithelial cell adhesion.",2013 Apr 17,"['Mima, Junko', 'Koshino, Aya', 'Oka, Kyoko', 'Uchida, Hitoshi', 'Hieda, Yohki', 'Nohara, Kanji', 'Kogo, Mikihiko', 'Chai, Yang', 'Sakai, Takayoshi']",PLoS One,,,True
2e905d86f4b7a8cb748864eb560c6555816fb0f1,PMC,Identification of Hepatotropic Viruses from Plasma Using Deep Sequencing: A Next Generation Diagnostic Tool,http://dx.doi.org/10.1371/journal.pone.0060595,PMC3629200,23613733,CC BY,"We conducted an unbiased metagenomics survey using plasma from patients with chronic hepatitis B, chronic hepatitis C, autoimmune hepatitis (AIH), non-alcoholic steatohepatitis (NASH), and patients without liver disease (control). RNA and DNA libraries were sequenced from plasma filtrates enriched in viral particles to catalog virus populations. Hepatitis viruses were readily detected at high coverage in patients with chronic viral hepatitis B and C, but only a limited number of sequences resembling other viruses were found. The exception was a library from a patient diagnosed with hepatitis C virus (HCV) infection that contained multiple sequences matching GB virus C (GBV-C). Abundant GBV-C reads were also found in plasma from patients with AIH, whereas Torque teno virus (TTV) was found at high frequency in samples from patients with AIH and NASH. After taxonomic classification of sequences by BLASTn, a substantial fraction in each library, ranging from 35% to 76%, remained unclassified. These unknown sequences were assembled into scaffolds along with virus, phage and endogenous retrovirus sequences and then analyzed by BLASTx against the non-redundant protein database. Nearly the full genome of a heretofore-unknown circovirus was assembled and many scaffolds that encoded proteins with similarity to plant, insect and mammalian viruses. The presence of this novel circovirus was confirmed by PCR. BLASTx also identified many polypeptides resembling nucleo-cytoplasmic large DNA viruses (NCLDV) proteins. We re-evaluated these alignments with a profile hidden Markov method, HHblits, and observed inconsistencies in the target proteins reported by the different algorithms. This suggests that sequence alignments are insufficient to identify NCLDV proteins, especially when these alignments are only to small portions of the target protein. Nevertheless, we have now established a reliable protocol for the identification of viruses in plasma that can also be adapted to other patient samples such as urine, bile, saliva and other body fluids.",2013 Apr 17,"['Law, John', 'Jovel, Juan', 'Patterson, Jordan', 'Ford, Glenn', 'O’keefe, Sandra', 'Wang, Weiwei', 'Meng, Bo', 'Song, Deyong', 'Zhang, Yong', 'Tian, Zhijian', 'Wasilenko, Shawn T.', 'Rahbari, Mandana', 'Mitchell, Troy', 'Jordan, Tracy', 'Carpenter, Eric', 'Mason, Andrew L.', 'Wong, Gane Ka-Shu']",PLoS One,,,True
de2ae20e4362e57c914f6bf1b9c51e0a4d90bfe1,PMC,Identification of Hepatotropic Viruses from Plasma Using Deep Sequencing: A Next Generation Diagnostic Tool,http://dx.doi.org/10.1371/journal.pone.0060595,PMC3629200,23613733,CC BY,"We conducted an unbiased metagenomics survey using plasma from patients with chronic hepatitis B, chronic hepatitis C, autoimmune hepatitis (AIH), non-alcoholic steatohepatitis (NASH), and patients without liver disease (control). RNA and DNA libraries were sequenced from plasma filtrates enriched in viral particles to catalog virus populations. Hepatitis viruses were readily detected at high coverage in patients with chronic viral hepatitis B and C, but only a limited number of sequences resembling other viruses were found. The exception was a library from a patient diagnosed with hepatitis C virus (HCV) infection that contained multiple sequences matching GB virus C (GBV-C). Abundant GBV-C reads were also found in plasma from patients with AIH, whereas Torque teno virus (TTV) was found at high frequency in samples from patients with AIH and NASH. After taxonomic classification of sequences by BLASTn, a substantial fraction in each library, ranging from 35% to 76%, remained unclassified. These unknown sequences were assembled into scaffolds along with virus, phage and endogenous retrovirus sequences and then analyzed by BLASTx against the non-redundant protein database. Nearly the full genome of a heretofore-unknown circovirus was assembled and many scaffolds that encoded proteins with similarity to plant, insect and mammalian viruses. The presence of this novel circovirus was confirmed by PCR. BLASTx also identified many polypeptides resembling nucleo-cytoplasmic large DNA viruses (NCLDV) proteins. We re-evaluated these alignments with a profile hidden Markov method, HHblits, and observed inconsistencies in the target proteins reported by the different algorithms. This suggests that sequence alignments are insufficient to identify NCLDV proteins, especially when these alignments are only to small portions of the target protein. Nevertheless, we have now established a reliable protocol for the identification of viruses in plasma that can also be adapted to other patient samples such as urine, bile, saliva and other body fluids.",2013 Apr 17,"['Law, John', 'Jovel, Juan', 'Patterson, Jordan', 'Ford, Glenn', 'O’keefe, Sandra', 'Wang, Weiwei', 'Meng, Bo', 'Song, Deyong', 'Zhang, Yong', 'Tian, Zhijian', 'Wasilenko, Shawn T.', 'Rahbari, Mandana', 'Mitchell, Troy', 'Jordan, Tracy', 'Carpenter, Eric', 'Mason, Andrew L.', 'Wong, Gane Ka-Shu']",PLoS One,,,False
5a4760a109394f2d59a82a5831c23ab7ac259eb2,PMC,Trends in North American Newspaper Reporting of Brain Injury in Ice Hockey,http://dx.doi.org/10.1371/journal.pone.0061865,PMC3629225,23613957,CC BY,"The frequency and potential long-term effects of sport-related traumatic brain injuries (TBI) make it a major public health concern. The culture within contact sports, such as ice hockey, encourages aggression that puts youth at risk of TBI such as concussion. Newspaper reports play an important role in conveying and shaping the culture around health-related behaviors. We qualitatively studied reports about sport-related TBI in four major North American newspapers over the last quarter-century. We used the grounded-theory approach to identify major themes and then did a content analysis to compare the frequency of key themes between 1998–2000 and 2009–2011. The major themes were: perceptions of brain injury, aggression, equipment, rules and regulations, and youth hockey. Across the full study period, newspaper articles from Canada and America portrayed violence and aggression that leads to TBI both as integral to hockey and as an unavoidable risk associated with playing the game. They also condemned violence in ice hockey, criticized the administrative response to TBI, and recognized the significance of TBI. In Canada, aggression was reported more often recently and there was a distinctive shift in portraying protective equipment as a solution to TBI in earlier years to a potential contributing factor to TBI later in the study period. American newspapers gave a greater attention to ‘perception of risks’ and the role of protective equipment, and discussed TBI in a broader context in the recent time period. Newspapers from both countries showed similar recent trends in regards to a need for rule changes to curb youth sport-related TBI. This study provides a rich description of the reporting around TBI in contact sport. Understanding this reporting is important for evaluating whether the dangers of sport-related TBI are being appropriately communicated by the media.",2013 Apr 17,"['Cusimano, Michael D.', 'Sharma, Bhanu', 'Lawrence, David W.', 'Ilie, Gabriela', 'Silverberg, Sarah', 'Jones, Rochelle']",PLoS One,,,True
7d9f6bae2b7ced5834b4e92e7ef805d85fdea405,PMC,Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus,http://dx.doi.org/10.1371/journal.pntd.0002181,PMC3630143,23638202,CC BY,"Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.",2013 Apr 18,"['Lihoradova, Olga A.', 'Indran, Sabarish V.', 'Kalveram, Birte', 'Lokugamage, Nandadeva', 'Head, Jennifer A.', 'Gong, Bin', 'Tigabu, Bersabeh', 'Juelich, Terry L.', 'Freiberg, Alexander N.', 'Ikegami, Tetsuro']",PLoS Negl Trop Dis,,,True
d39202d51ca886b55a141cad30f55b5443395048,PMC,Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus,http://dx.doi.org/10.1371/journal.pntd.0002181,PMC3630143,23638202,CC BY,"Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.",2013 Apr 18,"['Lihoradova, Olga A.', 'Indran, Sabarish V.', 'Kalveram, Birte', 'Lokugamage, Nandadeva', 'Head, Jennifer A.', 'Gong, Bin', 'Tigabu, Bersabeh', 'Juelich, Terry L.', 'Freiberg, Alexander N.', 'Ikegami, Tetsuro']",PLoS Negl Trop Dis,,,False
9fbfc291377589c67d526d29be532102bce9812f,PMC,Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus,http://dx.doi.org/10.1371/journal.pntd.0002181,PMC3630143,23638202,CC BY,"Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.",2013 Apr 18,"['Lihoradova, Olga A.', 'Indran, Sabarish V.', 'Kalveram, Birte', 'Lokugamage, Nandadeva', 'Head, Jennifer A.', 'Gong, Bin', 'Tigabu, Bersabeh', 'Juelich, Terry L.', 'Freiberg, Alexander N.', 'Ikegami, Tetsuro']",PLoS Negl Trop Dis,,,False
bc2afee8129278e494059eee1c725462bc343456,PMC,Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus,http://dx.doi.org/10.1371/journal.pntd.0002181,PMC3630143,23638202,CC BY,"Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.",2013 Apr 18,"['Lihoradova, Olga A.', 'Indran, Sabarish V.', 'Kalveram, Birte', 'Lokugamage, Nandadeva', 'Head, Jennifer A.', 'Gong, Bin', 'Tigabu, Bersabeh', 'Juelich, Terry L.', 'Freiberg, Alexander N.', 'Ikegami, Tetsuro']",PLoS Negl Trop Dis,,,False
6e4cbb8df1a37cf1dbcd398741b01accafde7c2b,PMC,Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus,http://dx.doi.org/10.1371/journal.pntd.0002181,PMC3630143,23638202,CC BY,"Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.",2013 Apr 18,"['Lihoradova, Olga A.', 'Indran, Sabarish V.', 'Kalveram, Birte', 'Lokugamage, Nandadeva', 'Head, Jennifer A.', 'Gong, Bin', 'Tigabu, Bersabeh', 'Juelich, Terry L.', 'Freiberg, Alexander N.', 'Ikegami, Tetsuro']",PLoS Negl Trop Dis,,,False
d745e9cbecf81be30e9ffe290781acea84fbd9d3,PMC,The Development and Application of the Two Real-Time RT-PCR Assays to Detect the Pathogen of HFMD,http://dx.doi.org/10.1371/journal.pone.0061451,PMC3630163,23637836,CC BY,"Large-scale Hand, Foot, and Mouth Disease (HFMD) outbreaks have frequently occurred in China since 2008, affecting more than one million children and causing several hundred children deaths every year. The pathogens of HFMD are mainly human enteroviruses (HEVs). Among them, human enterovirus 71 (HEV71) and coxsackievirus A16 (CVA16) are the most common pathogens of HFMD. However, other HEVs could also cause HFMD. To rapidly detect HEV71 and CVA16, and ensure detection of all HEVs causing HFMD, two real-time hybridization probe-based RT-PCR assays were developed in this study. One is a multiplex real-time RT-PCR assay, which was developed to detect and differentiate HEV71 specifically from CVA16 directly from clinical specimens within 1–2 h, and the other is a broad-spectrum real-time RT-PCR assay, which targeted almost all HEVs. The experiments confirmed that the two assays have high sensitivity and specificity, and the sensitivity was up to 0.1 TCID(50)/ml for detection of HEVs, HEV71, and CVA16, respectively. A total of 213 clinical specimens were simultaneously detected by three kinds of assays, including the two real-time RT-PCR assays, direct conventional RT-PCR assay, and virus isolation assay on human rhabdomyosarcoma cells (RD cells). The total positive rate of both HEV71 and CVA16 was 69.48% with real-time RT-PCR assay, 47.42% with RT-PCR assay, and 34.58% with virus isolation assay. One HFMD clinical specimen was positive for HEV, but negative for HEV71 or CVA16, which was identified as Echovirus 11 (Echo11) by virus isolation, RT-PCR, and sequencing for the VP1 gene. The two real-time RT-PCR assays had been applied in 31 provincial HFMD labs to detect the pathogens of HFMD, which has contributed to the rapid identification of the pathogens in the early stages of HFMD outbreaks, and helped to clarify the etiologic agents of HFMD in China.",2013 Apr 18,"['Cui, Aili', 'Xu, Changping', 'Tan, Xiaojuan', 'Zhang, Yan', 'Zhu, Zhen', 'Mao, Naiying', 'Lu, Yiyu', 'Xu, Wenbo']",PLoS One,,,True
fbc5981e0920859187fee6c4243de58c9906f2ee,PMC,Complete Genome Sequence of a Recombinant Porcine Epidemic Diarrhea Virus Strain from Eastern China,http://dx.doi.org/10.1128/genomeA.00105-13,PMC3630398,23599287,CC BY,"A field porcine epidemic diarrhea virus (PEDV) strain, JS2008, was isolated from stool samples of a piglet with acute diarrhea on a vaccinated farm in eastern China. We sequenced and analyzed the complete genome of strain JS2008, which will help increase our understanding of the molecular characteristics of the epidemic PEDV in China.",2013 Apr 18,"['Li, Bin', 'Liu, Haofei', 'He, Kongwang', 'Guo, Rongli', 'Ni, Yanxiu', 'Du, Luping', 'Wen, Libin', 'Zhang, Xuehan', 'Yu, Zhengyu', 'Zhou, Junming', 'Mao, Aihua', 'Lv, Lixin', 'Hu, Yiyi', 'Yu, Yang', 'Zhu, Haodan', 'Wang, Xiaomin']",Genome Announc,,,True
707a1297b8ac950819a217102e5f4847a67b48c7,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,True
ecb3e7e1fdbb54d79d3b547fd4a4a44556c8f2f4,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
3695c79392a4adf72bfc7fa54125d3b5940967be,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
96c3708909d821152cedd5dff77196abcb2f2c92,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
52b222b674264d7e3d125dd0d36176b74642657e,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
9a5f67fedb2b14a2baf19e3b2cf2f6fff0ff7921,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
d2514e372c5ddf1d335efc9bca1e8d61b15df4cf,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
34fb3171b67b9a98bf2f5c6474d9fe6d5975a2bc,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
08dcd85ac15d14a2a14d1c81308ee516065282b0,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
966e2ff5e39796c7a3337620cb4167f780d18aea,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
5903202b5bdbfa366926099e3f46ed2fd6c65fef,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,False
40c76ef7831f3e2df1619e05514849a67a07d5d6,PMC,Marked Variability in the Extent of Protein Disorder within and between Viral Families,http://dx.doi.org/10.1371/journal.pone.0060724,PMC3631256,23620725,CC BY,"Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs) embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues), and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively). Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses), except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel instances of SLiMs subverting host functions, such as innate and acquired immunity.",2013 Apr 19,"['Pushker, Ravindra', 'Mooney, Catherine', 'Davey, Norman E.', 'Jacqué, Jean-Marc', 'Shields, Denis C.']",PLoS One,,,True
4ce340ef89eb6535f11ace1d627d98e619e2d17b,PMC,Virome Profiling of Bats from Myanmar by Metagenomic Analysis of Tissue Samples Reveals More Novel Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0061950,PMC3632529,23630620,CC BY,"Bats are reservoir animals harboring many important pathogenic viruses and with the capability of transmitting these to humans and other animals. To establish an effective surveillance to monitor transboundary spread of bat viruses between Myanmar and China, complete organs from the thorax and abdomen from 853 bats of six species from two Myanmar counties close to Yunnan province, China, were collected and tested for their virome through metagenomics by Solexa sequencing and bioinformatic analysis. In total, 3,742,314 reads of 114 bases were generated, and over 86% were assembled into 1,649,512 contigs with an average length of 114 bp, of which 26,698 (2%) contigs were recognizable viral sequences belonging to 24 viral families. Of the viral contigs 45% (12,086/26,698) were related to vertebrate viruses, 28% (7,443/26,698) to insect viruses, 27% (7,074/26,698) to phages and 95 contigs to plant viruses. The metagenomic results were confirmed by PCR of selected viruses in all bat samples followed by phylogenetic analysis, which has led to the discovery of some novel bat viruses of the genera Mamastrovirus, Bocavirus, Circovirus, Iflavirus and Orthohepadnavirus and to their prevalence rates in two bat species. In conclusion, the present study aims to present the bat virome in Myanmar, and the results obtained further expand the spectrum of viruses harbored by bats.",2013 Apr 22,"['He, Biao', 'Li, Zuosheng', 'Yang, Fanli', 'Zheng, Junfeng', 'Feng, Ye', 'Guo, Huancheng', 'Li, Yingying', 'Wang, Yiyin', 'Su, Nan', 'Zhang, Fuqiang', 'Fan, Quanshui', 'Tu, Changchun']",PLoS One,,,True
fd990c95b7300a2e18a8be156f159943246e06b5,PMC,Citrus tristeza virus: Evolution of Complex and Varied Genotypic Groups,http://dx.doi.org/10.3389/fmicb.2013.00093,PMC3632782,23630519,CC BY,"Amongst the Closteroviridae, Citrus tristeza virus (CTV) is almost unique in possessing a number of distinct and characterized strains, isolates of which produce a wide range of phenotype combinations among its different hosts. There is little understanding to connect genotypes to phenotypes, and to complicate matters more, these genotypes are found throughout the world as members of mixed populations within a single host plant. There is essentially no understanding of how combinations of genotypes affect symptom expression and disease severity. We know little about the evolution of the genotypes that have been characterized to date, little about the biological role of their diversity and particularly, about the effects of recombination. Additionally, genotype grouping has not been standardized. In this study we utilized an extensive array of CTV genomic information to classify the major genotypes, and to determine the major evolutionary processes that led to their formation and subsequent retention. Our analyses suggest that three major processes act on these genotypes: (1) ancestral diversification of the major CTV lineages, followed by (2) conservation and co-evolution of the major functional domains within, though not between CTV genotypes, and (3) extensive recombination between lineages that have given rise to new genotypes that have subsequently been retained within the global population. The effects of genotype diversity and host-interaction are discussed, as is a proposal for standardizing the classification of existing and novel CTV genotypes.",2013 Apr 23,"Harper, S. J.",Front Microbiol,,,True
76d39ac4634db5a0fcc8cddbefd965c463c0ace0,PMC,"Decreased Pattern Recognition Receptor Signaling, Interferon-Signature, and Bactericidal/Permeability-Increasing Protein Gene Expression in Cord Blood of Term Low Birth Weight Human Newborns",http://dx.doi.org/10.1371/journal.pone.0062845,PMC3633842,23626859,CC BY,"BACKGROUND: Morbidity and mortality rates of low birth weight (LBW) newborns at term are higher than rates in normal birth weight (NBW) newborns. LBW newborns are at greater risk to acquire recurrent bacterial and viral infections during their first few weeks of life possibly as an outcome of compromised innate immune functions. As adaptive immunity is in a naive state, increased risk of infection of LBW as compared to NBW newborns may reflect impairments in innate immunity. METHODOLOGY: To characterize the increased susceptibility to infections in LBW newborns we used microarray technology to identify differences in gene expression in LBW newborns (n = 8) compared to NBW newborns (n = 4) using cord blood. The results obtained from the microarray study were validated on a larger number of samples using real time RT-PCR (LBW = 22, NBW = 18) and western blotting (LBW = 12, NBW = 12). The Interferome database was used to identify interferon (IFN) signature genes and ingenuity pathway analysis identified canonical pathways and biological functions associated with the differentially expressed genes in LBW newborns. ELISAs for IFNs and bactericidal/permeability-increasing protein were performed in both LBW and NBW newborns and in adults (LBW = 18, NBW = 18, Adults = 8). PRINCIPAL FINDINGS: Upon microarray analysis, we identified 1,391 differentially expressed genes, of which, 1,065 genes were down-regulated and 326 genes were up-regulated in the LBW compared to NBW newborns. Of note, 70 IFN-signature genes were found to be significantly down-regulated in LBW compared to NBW newborns. Ingenuity pathway analysis revealed pattern recognition receptors signaling including Toll-Like Receptors (TLRs) -1, -5, and -8 genes and IFN signaling as the most significantly impacted pathways. Respiratory infectious diseases were the most significantly affected bio-functions in LBW newborns. CONCLUSION AND SIGNIFICANCE: Diminished PRRs, IFN-signature, and BPI gene expression raises the possibility that impairments in these pathways contribute to the susceptibility of LBW term infants to infection.",2013 Apr 23,"['Singh, Vikas Vikram', 'Chauhan, Sudhir Kumar', 'Rai, Richa', 'Kumar, Ashok', 'Singh, Shiva M.', 'Rai, Geeta']",PLoS One,,,True
1b3ea086b81a5e0c4dd22aa41653befc358d7163,PMC,Immunopathogenesis of Severe Acute Respiratory Disease in Zaire ebolavirus-Infected Pigs,http://dx.doi.org/10.1371/journal.pone.0061904,PMC3633953,23626748,CC BY,"Ebola viruses (EBOV) are filamentous single-stranded RNA viruses of the family Filoviridae. Zaire ebolavirus (ZEBOV) causes severe haemorrhagic fever in humans, great apes and non-human primates (NHPs) with high fatality rates. In contrast, Reston ebolavirus (REBOV), the only species found outside Africa, is lethal to some NHPs but has never been linked to clinical disease in humans despite documented exposure. REBOV was isolated from pigs in the Philippines and subsequent experiments confirmed the susceptibility of pigs to both REBOV and ZEBOV with predilection for the lungs. However, only ZEBOV caused severe lung pathology in 5–6 weeks old pigs leading to respiratory distress. To further elucidate the mechanisms for lung pathology, microarray analysis of changes in gene expression was performed on lung tissue from ZEBOV-infected pigs. Furthermore, systemic effects were monitored by looking at changes in peripheral blood leukocyte subsets and systemic cytokine responses. Following oro-nasal challenge, ZEBOV replicated mainly in the respiratory tract, causing severe inflammation of the lungs and consequently rapid and difficult breathing. Neutrophils and macrophages infiltrated the lungs but only the latter were positive for ZEBOV antigen. Genes for proinflammatory cytokines, chemokines and acute phase proteins, known to attract immune cells to sites of infection, were upregulated in the lungs, causing the heavy influx of cells into this site. Systemic effects included a decline in the proportion of monocyte/dendritic and B cells and a mild proinflammatory cytokine response. Serum IgM was detected on day 5 and 6 post infection. In conclusion, a dysregulation/over-activation of the pulmonary proinflammatory response may play a crucial role in the pathogenesis of ZEBOV infection in 5–6 weeks old pigs by attracting inflammatory cells to the lungs.",2013 Apr 23,"['Nfon, Charles K.', 'Leung, Anders', 'Smith, Greg', 'Embury-Hyatt, Carissa', 'Kobinger, Gary', 'Weingartl, Hana M.']",PLoS One,,,True
b55320e1004341c20c8b61cca6a2bb47c0dc4d59,PMC,9G DNAChip Technology: Self-Assembled Monolayer (SAM) of ssDNA for Ultra-Sensitive Detection of Biomarkers,http://dx.doi.org/10.3390/ijms14035723,PMC3634481,23481635,CC BY,"A 9G DNAChip obtained by allowing the formation of a self-assembled monolayer (SAM) of oligonucleotides appended with nine consecutive guanines on the chip surface has been applied in the detection of biomarkers. Using a 9G DNAChip, biomarker in the concentration range of 4 pg/mL to 40 fg/mL can be easily differentiated in the buffer matrix. Moreover, it is the first time that a biomarker with a concentration of 40 fg/mL has been detected in a mixture of proteins without use of any signal amplification technique.",2013 Mar 12,"['Nimse, Satish Balasaheb', 'Song, Keum-Soo', 'Kim, Junghoon', 'Sayyed, Danishmalik Rafiq', 'Kim, Taisun']",Int J Mol Sci,,,True
f2ed0201813317b17f4e6b34058b9a45a2ba8c63,PMC,9G DNAChip Technology: Self-Assembled Monolayer (SAM) of ssDNA for Ultra-Sensitive Detection of Biomarkers,http://dx.doi.org/10.3390/ijms14035723,PMC3634481,23481635,CC BY,"A 9G DNAChip obtained by allowing the formation of a self-assembled monolayer (SAM) of oligonucleotides appended with nine consecutive guanines on the chip surface has been applied in the detection of biomarkers. Using a 9G DNAChip, biomarker in the concentration range of 4 pg/mL to 40 fg/mL can be easily differentiated in the buffer matrix. Moreover, it is the first time that a biomarker with a concentration of 40 fg/mL has been detected in a mixture of proteins without use of any signal amplification technique.",2013 Mar 12,"['Nimse, Satish Balasaheb', 'Song, Keum-Soo', 'Kim, Junghoon', 'Sayyed, Danishmalik Rafiq', 'Kim, Taisun']",Int J Mol Sci,,,False
a0e91efcafa0a743be0342254943e8d31cd36558,PMC,A Study of the Mechanism of the Chaperone-like Function of an scFv of Human Creatine Kinase by Computer Simulation,http://dx.doi.org/10.1371/journal.pone.0062147,PMC3634753,23637984,CC BY,"A new application of antibodies is to use them as macromolecular chaperones. Protein antigens usually have multiple epitopes, thus, there may be a plurality of antibodies binding to one antigen. However, not all antibodies that bind to one antigen could act as a chaperone. Experiments show that some screened anti-human creatine kinase single chain antibodies (scFV) could assist in the folding and stabilizing of the enzyme, while others could not. We built the model of the single chain antibody (scFv-A4) that increased the stability of human creatine kinase (HCK) by the homology modeling method. Epitopes of human creatine kinase were predicted by computer and then the binding of scFv-A4 and HCK was modeled with computer. The calculation results were further combined with the peptide array membrane experiment results to obtain reliable models for the scFv-A4-HCK complex. Based on the above study we gave an explanation about how scFv-A4 could act as a macromolecular chaperone assisting the folding of HCK. This study provides an approach for predicting antigen-antibody binding mode and also a useful theoretical guidance for the study of antibodies' chaperone-like function.",2013 Apr 24,"['Feng, Jianyu', 'Guo, Hong', 'Li, Sen', 'Lu, Tun']",PLoS One,,,True
9a98026855729dd7aa175ca9ed534a73c7fd9a84,PMC,HCV-Induced miR-21 Contributes to Evasion of Host Immune System by Targeting MyD88 and IRAK1,http://dx.doi.org/10.1371/journal.ppat.1003248,PMC3635988,23633945,CC BY,"Upon recognition of viral components by pattern recognition receptors, such as the toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like helicases, cells are activated to produce type I interferon (IFN) and proinflammatory cytokines. These pathways are tightly regulated by the host to prevent an inappropriate cellular response, but viruses can modulate these pathways to proliferate and spread. In this study, we revealed a novel mechanism in which hepatitis C virus (HCV) evades the immune surveillance system to proliferate by activating microRNA-21 (miR-21). We demonstrated that HCV infection upregulates miR-21, which in turn suppresses HCV-triggered type I IFN production, thus promoting HCV replication. Furthermore, we demonstrated that miR-21 targets two important factors in the TLR signaling pathway, myeloid differentiation factor 88 (MyD88) and interleukin-1 receptor-associated kinase 1 (IRAK1), which are involved in HCV-induced type I IFN production. HCV-mediated activation of miR-21 expression requires viral proteins and several signaling components. Moreover, we identified a transcription factor, activating protein-1 (AP-1), which is partly responsible for miR-21 induction in response to HCV infection through PKCε/JNK/c-Jun and PKCα/ERK/c-Fos cascades. Taken together, our results indicate that miR-21 is upregulated during HCV infection and negatively regulates IFN-α signaling through MyD88 and IRAK1 and may be a potential therapeutic target for antiviral intervention.",2013 Apr 25,"['Chen, Yanni', 'Chen, Junbo', 'Wang, Hui', 'Shi, Jingjing', 'Wu, Kailang', 'Liu, Shi', 'Liu, Yingle', 'Wu, Jianguo']",PLoS Pathog,,,True
985bcaae91f49b39ffb29301edef221c46c66034,PMC,Systems Analysis of a RIG-I Agonist Inducing Broad Spectrum Inhibition of Virus Infectivity,http://dx.doi.org/10.1371/journal.ppat.1003298,PMC3635991,23633948,CC BY,"The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5′ triphosphate (5′ppp) terminal structure. In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range. In human lung epithelial A549 cells, 5′pppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, and induction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response. Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN) signaling. Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5′pppRNA, and not by IFNα-2b, that included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response. Treatment of primary PBMCs or lung epithelial A549 cells with 5′pppRNA provided significant protection against a spectrum of RNA and DNA viruses. In C57Bl/6 mice, intravenous administration of 5′pppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia. Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling. This systems approach provides transcriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5′pppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents.",2013 Apr 25,"['Goulet, Marie-Line', 'Olagnier, David', 'Xu, Zhengyun', 'Paz, Suzanne', 'Belgnaoui, S. Mehdi', 'Lafferty, Erin I.', 'Janelle, Valérie', 'Arguello, Meztli', 'Paquet, Marilene', 'Ghneim, Khader', 'Richards, Stephanie', 'Smith, Andrew', 'Wilkinson, Peter', 'Cameron, Mark', 'Kalinke, Ulrich', 'Qureshi, Salman', 'Lamarre, Alain', 'Haddad, Elias K.', 'Sekaly, Rafick Pierre', 'Peri, Suraj', 'Balachandran, Siddharth', 'Lin, Rongtuan', 'Hiscott, John']",PLoS Pathog,,,True
bdbfaa82df2210193903b96916ffe6fed13694b4,PMC,Inactivation of an enterovirus by airborne disinfectants,http://dx.doi.org/10.1186/1471-2334-13-177,PMC3636024,23587047,CC BY,"BACKGROUND: The activity of airborne disinfectants on bacteria, fungi and spores has been reported. However, the issue of the virucidal effect of disinfectants spread by fogging has not been studied thoroughly. METHODS: A procedure has been developed to determine the virucidal activity of peracetic acid-based airborne disinfectants on a resistant non-enveloped virus poliovirus type 1. This virus was laid on a stainless carrier. The products were spread into the room by hot fogging at 55°C for 30 minutes at a concentration of 7.5 mL.m(-3). Poliovirus inoculum, supplemented with 5%, heat inactivated non fat dry organic milk, were applied into the middle of the stainless steel disc and were dried under the air flow of a class II biological safety cabinet at room temperature. The Viral preparations were recovered by using flocked swabs and were titered on Vero cells using the classical Spearman-Kärber CPE reading method, the results were expressed as TCID50.ml(-1). RESULTS: The infectious titer of dried poliovirus inocula was kept at 10(5) TCID(50).mL(-1) up to 150 minutes at room temperature. Dried inocula exposed to airborne peracetic acid containing disinfectants were recovered at 60 and 120 minutes post-exposition and suspended in culture medium again. The cytotoxicity of disinfectant containing medium was eliminated through gel filtration columns. A 4 log reduction of infectious titer of dried poliovirus inocula exposed to peracetic-based airborne disinfectant was obtained. CONCLUSION: This study demonstrates that the virucidal activity of airborne disinfectants can be tested on dried poliovirus.",2013 Apr 15,"['Thevenin, Thomas', 'Lobert, Pierre-Emmanuel', 'Hober, Didier']",BMC Infect Dis,,,True
3eb3c6212432888ecf0f2d3d2dc4a2fb6b4f17c0,PMC,CGAP: a new comprehensive platform for the comparative analysis of chloroplast genomes,http://dx.doi.org/10.1186/1471-2105-14-95,PMC3636126,23496817,CC BY,"BACKGROUND: Chloroplast is an essential organelle in plants which contains independent genome. Chloroplast genomes have been widely used for plant phylogenetic inference recently. The number of complete chloroplast genomes increases rapidly with the development of various genome sequencing projects. However, no comprehensive platform or tool has been developed for the comparative and phylogenetic analysis of chloroplast genomes. Thus, we constructed a comprehensive platform for the comparative and phylogenetic analysis of complete chloroplast genomes which was named as chloroplast genome analysis platform (CGAP). RESULTS: CGAP is an interactive web-based platform which was designed for the comparative analysis of complete chloroplast genomes. CGAP integrated genome collection, visualization, content comparison, phylogeny analysis and annotation functions together. CGAP implemented four web servers including creating complete and regional genome maps of high quality, comparing genome features, constructing phylogenetic trees using complete genome sequences, and annotating draft chloroplast genomes submitted by users. CONCLUSIONS: Both CGAP and source code are available at http://www.herbbol.org:8000/chloroplast. CGAP will facilitate the collection, visualization, comparison and annotation of complete chloroplast genomes. Users can customize the comparative and phylogenetic analysis using their own unpublished chloroplast genomes.",2013 Mar 14,"['Cheng, Jinkui', 'Zeng, Xu', 'Ren, Guomin', 'Liu, Zhihua']",BMC Bioinformatics,,,True
72e1bab73b7f05d68543660981e0c8cef749c045,PMC,"Accuracy of IgM antibody testing, FQ-PCR and culture in laboratory diagnosis of acute infection by Mycoplasma pneumoniae in adults and adolescents with community-acquired pneumonia",http://dx.doi.org/10.1186/1471-2334-13-172,PMC3637260,23578215,CC BY,"BACKGROUND: Diagnosis of community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae in adults and adolescents is hampered by a lack of rapid and standardized tests for detection. METHODS: CAP patients from 12 teaching hospitals were prospectively and consecutively recruited. Basic and clinical information, throat swabs and paired sera were collected. Mycoplasma pneumoniae was detected by IgG and IgM antibody tests, fluorescence quantitative polymerase chain reaction (FQ-PCR) and culture. A comparative study of the diagnostic values of three methods, including sensitivity, specificity, positive and negative predictive values and positive likelihood ratio (PLR) was conducted. A fourfold or greater increase of IgG antibody titers of paired sera was set as the diagnostic “gold standard”. RESULTS: One hundred and twenty-five CAP patients (52.8% males, median age 47 years, range 14–85) were enrolled. Twenty-seven (21.6%) patients were diagnosed with acute Mycoplasma pneumoniae infections by the “gold standard”. Specificity values of all three methods were around 90%. An increasing trend of sensitivity, positive predictive value and PLR was found, with the lowest in IgM testing (7.4%, 28.6% and 1.45), intermediate in FQ-PCR (40.7%, 50% and 3.63), and highest in culture (55.6%, 75% and 10.9). CONCLUSIONS: In the defined group of patients, there was a good agreement between positive rate of MP cultivation of throat swabs and acute M. pneumoniae infection (PLR of 10.9). Since the sensitivity is low in all of the evaluated methods, the logical approach would be to incorporate PCR, culture and serological tests for optimum diagnosis of acute Mycoplasma pneumoniae infections in adults and adolescents.",2013 Apr 11,"['Qu, Jiuxin', 'Gu, Li', 'Wu, Jiang', 'Dong, Jianping', 'Pu, Zenghui', 'Gao, Yan', 'Hu, Ming', 'Zhang, Yongxiang', 'Gao, Feng', 'Cao, Bin', 'Wang, Chen']",BMC Infect Dis,,,True
40c1f536d2ba1ea36ff1f17881df3f1073e76586,PMC,Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events,http://dx.doi.org/10.1186/1479-5876-11-75,PMC3637501,23521917,CC BY,"BACKGROUND: Treatment with ipilimumab, a fully human anti-CTLA-4 antibody approved for the treatment of advanced melanoma, is associated with some immune-related adverse events (irAEs) such as colitis (gastrointestinal irAE, or GI irAE) and skin rash, which are managed by treatment guidelines. Nevertheless, predictive biomarkers that can help identify patients more likely to develop these irAEs could enhance the management of these toxicities. METHODS: To identify candidate predictive biomarkers associated with GI irAEs, gene expression profiling was performed on whole blood samples from 162 advanced melanoma patients at baseline, 3 and 11 weeks after the start of ipilimumab treatment in two phase II clinical trials (CA184004 and CA184007). Overall, 49 patients developed Grade 2 or higher (grade 2+) GI irAEs during the course of treatment. A repeated measures analysis of variance (ANOVA) was used to evaluate the differences in mean expression levels between the GI irAE and No-GI irAE groups of patients at the three time points. RESULTS: In baseline samples, 27 probe sets showed differential mean expression (≥ 1.5 fold, P ≤ 0.05) between the GI irAE and No-GI irAE groups. Most of these probe sets belonged to three functional categories: immune system, cell cycle, and intracellular trafficking. Changes in gene expression over time were also characterized. In the GI irAE group, 58 and 247 probe sets had a ≥ 1.5 fold change in expression from baseline to 3 and 11 weeks after first ipilimumab dose, respectively. In particular, on-treatment expression increases of CD177 and CEACAM1, two neutrophil-activation markers, were closely associated with GI irAEs, suggesting a possible role of neutrophils in ipilimumab-associated GI irAEs. In addition, the expression of several immunoglobulin genes increased over time, with greater increases in patients with grade 2+ GI irAEs. CONCLUSIONS: Gene expression profiling of peripheral blood, sampled before or early in the course of treatment with ipilimumab, resulted in the identification of a set of potential biomarkers that were associated with occurrence of GI irAEs. However, because of the low sensitivity of these biomarkers, they cannot be used alone to predict which patients will develop GI irAEs. Further investigation of these biomarkers in a larger patient cohort is warranted.",2013 Mar 22,"['Shahabi, Vafa', 'Berman, David', 'Chasalow, Scott D', 'Wang, Lisu', 'Tsuchihashi, Zenta', 'Hu, Beihong', 'Panting, Lisa', 'Jure-Kunkel, Maria', 'Ji, Rui-Ru']",J Transl Med,,,True
6fe01cb9f2b36418bd0f5a17bc665e2e02fd2460,PMC,ACE2-Ang-(1-7)-Mas Axis in Brain: A Potential Target for Prevention and Treatment of Ischemic Stroke,http://dx.doi.org/10.2174/1570159X11311020007,PMC3637674,23997755,CC BY,"The renin-angiotensin system (RAS) in brain is a crucial regulator for physiological homeostasis and diseases of cerebrovascular system, such as ischemic stroke. Overactivation of brain Angiotensin-converting enzyme (ACE) - Angiotensin II (Ang II) - Angiotensin II type 1 receptor (AT(1)R) axis was found to be involved in the progress of hypertension, atherosclerosis and thrombogenesis, which increased the susceptibility to ischemic stroke. Besides, brain Ang II levels have been revealed to be increased in ischemic tissues after stroke, and contribute to neural damage through elevating oxidative stress levels and inducing inflammatory response in the ischemic hemisphere via AT(1)R. In recent years, new components of RAS have been discovered, including ACE2, Angiotensin-(1–7) [Ang-(1-7)] and Mas, which constitute ACE2-Ang-(1-7)-Mas axis. ACE2 converts Ang II to Ang-(1-7), and Ang-(1-7) binds with its receptor Mas, exerting benefical effects in cerebrovascular disease. Through interacting with nitric oxide and bradykinin, Ang-(1-7) could attenuate the development of hypertension and the pathologic progress of atherosclerosis. Besides, its antithrombotic activity also prevents thrombogenic events, which may contribute to reduce the risk of ischemic stroke. In addition, after ischemia insult, ACE2-Ang-(1-7)-Mas has been shown to reduce the cerebral infarct size and improve neurological deficits through its antioxidative and anti-inflammatory effects. Taken together, activation of the ACE2-Ang-(1-7)-Mas axis may become a novel therapeutic target in prevention and treatment of ischemia stroke, which deserves further investigations.",2013 Mar,"['Jiang, Teng', 'Gao, Li', 'Lu, Jie', 'Zhang, Ying-Dong']",Curr Neuropharmacol,,,True
9e951559a8cbef877c02296db2e3c2f0ccc8ddec,PMC,Structural Complexity of DNA Sequence,http://dx.doi.org/10.1155/2013/628036,PMC3638703,23662161,CC BY,"In modern bioinformatics, finding an efficient way to allocate sequence fragments with biological functions is an important issue. This paper presents a structural approach based on context-free grammars extracted from original DNA or protein sequences. This approach is radically different from all those statistical methods. Furthermore, this approach is compared with a topological entropy-based method for consistency and difference of the complexity results.",2013 Apr 4,"['Liou, Cheng-Yuan', 'Tseng, Shen-Han', 'Cheng, Wei-Chen', 'Tsai, Huai-Ying']",Comput Math Methods Med,,,True
6a0c165fd5c40909228209e01112875b6d968dea,PMC,"Redescription of Hepatozoon felis (Apicomplexa: Hepatozoidae) based on phylogenetic analysis, tissue and blood form morphology, and possible transplacental transmission",http://dx.doi.org/10.1186/1756-3305-6-102,PMC3639113,23587213,CC BY,"BACKGROUND: A Hepatozoon parasite was initially reported from a cat in India in 1908 and named Leucocytozoon felis domestici. Although domestic feline hepatozoonosis has since been recorded from Europe, Africa, Asia and America, its description, classification and pathogenesis have remained vague and the distinction between different species of Hepatozoon infecting domestic and wild carnivores has been unclear. The aim of this study was to carry out a survey on domestic feline hepatozoonosis and characterize it morphologically and genetically. METHODS: Hepatozoon sp. DNA was amplified by PCR from the blood of 55 of 152 (36%) surveyed cats in Israel and from all blood samples of an additional 19 cats detected as parasitemic by microscopy during routine hematologic examinations. Hepatozoon sp. forms were also characterized from tissues of naturally infected cats. RESULTS: DNA sequencing determined that all cats were infected with Hepatozoon felis except for two infected by Hepatozoon canis. A significant association (p = 0.00001) was found between outdoor access and H. felis infection. H. felis meronts containing merozoites were characterized morphologically from skeletal muscles, myocardium and lungs of H. felis PCR-positive cat tissues and development from early to mature meront was described. Distinctly-shaped gamonts were observed and measured from the blood of these H. felis infected cats. Two fetuses from H. felis PCR-positive queens were positive by PCR from fetal tissue including the lung and amniotic fluid, suggesting possible transplacental transmission. Genetic analysis indicated that H. felis DNA sequences from Israeli cats clustered together with the H. felis Spain 1 and Spain 2 sequences. These cat H. felis sequences clustered separately from the feline H. canis sequences, which grouped with Israeli and foreign dog H. canis sequences. H. felis clustered distinctly from Hepatozoon spp. of other mammals. Feline hepatozoonosis caused by H. felis is mostly sub-clinical as a high proportion of the population is infected with no apparent overt clinical manifestations. CONCLUSIONS: This study aimed to integrate new histopathologic, hematologic, clinical, epidemiological and genetic findings on feline hepatozoonosis and promote the understanding of this infection. The results indicate that feline infection is primarily caused by a morphologically and genetically distinct species, H. felis, which has predilection to infecting muscular tissues, and is highly prevalent in the cat population studied. The lack of previous comprehensively integrated data merits the redescription of this parasite elucidating its parasitological characteristics.",2013 Apr 15,"['Baneth, Gad', 'Sheiner, Alina', 'Eyal, Osnat', 'Hahn, Shelley', 'Beaufils, Jean-Pierre', 'Anug, Yigal', 'Talmi-Frank, Dalit']",Parasit Vectors,,,True
ec2ecade86e6e7660bd8fc929ab0c602cdf16568,PMC,Identification of Residues of SARS-CoV nsp1 That Differentially Affect Inhibition of Gene Expression and Antiviral Signaling,http://dx.doi.org/10.1371/journal.pone.0062416,PMC3639174,23658627,CC BY,"An epidemic of Severe Acute Respiratory Syndrome (SARS) led to the identification of an associated coronavirus, SARS-CoV. This virus evades the host innate immune response in part through the expression of its non-structural protein (nsp) 1, which inhibits both host gene expression and virus- and interferon (IFN)-dependent signaling. Thus, nsp1 is a promising target for drugs, as inhibition of nsp1 would make SARS-CoV more susceptible to the host antiviral defenses. To gain a better understanding of nsp1 mode of action, we generated and analyzed 38 mutants of the SARS-CoV nsp1, targeting 62 solvent exposed residues out of the 180 amino acid protein. From this work, we identified six classes of mutants that abolished, attenuated or increased nsp1 inhibition of host gene expression and/or antiviral signaling. Each class of mutants clustered on SARS-CoV nsp1 surface and suggested nsp1 interacts with distinct host factors to exert its inhibitory activities. Identification of the nsp1 residues critical for its activities and the pathways involved in these activities should help in the design of drugs targeting nsp1. Significantly, several point mutants increased the inhibitory activity of nsp1, suggesting that coronaviruses could evolve a greater ability to evade the host response through mutations of such residues.",2013 Apr 29,"['Jauregui, Andrew R.', 'Savalia, Dhruti', 'Lowry, Virginia K.', 'Farrell, Cara M.', 'Wathelet, Marc G.']",PLoS One,,,True
90a7c8a2e1be47616b2f04bd011c148fcbc8adba,PMC,Regulation of Programmed Ribosomal Frameshifting by Co-Translational Refolding RNA Hairpins,http://dx.doi.org/10.1371/journal.pone.0062283,PMC3639245,23638024,CC BY,"RNA structures are unwound for decoding. In the process, they can pause the elongating ribosome for regulation. An example is the stimulation of -1 programmed ribosomal frameshifting, leading to 3′ direction slippage of the reading-frame during elongation, by specific pseudoknot stimulators downstream of the frameshifting site. By investigating a recently identified regulatory element upstream of the SARS coronavirus (SARS-CoV) −1 frameshifting site, it is shown that a minimal functional element with hairpin forming potential is sufficient to down-regulate−1 frameshifting activity. Mutagenesis to disrupt or restore base pairs in the potential hairpin stem reveals that base-pair formation is required for−1 frameshifting attenuation in vitro and in 293T cells. The attenuation efficiency of a hairpin is determined by its stability and proximity to the frameshifting site; however, it is insensitive to E site sequence variation. Additionally, using a dual luciferase assay, it can be shown that a hairpin stimulated +1 frameshifting when placed upstream of a +1 shifty site in yeast. The investigations indicate that the hairpin is indeed a cis-acting programmed reading-frame switch modulator. This result provides insight into mechanisms governing−1 frameshifting stimulation and attenuation. Since the upstream hairpin is unwound (by a marching ribosome) before the downstream stimulator, this study’s findings suggest a new mode of translational regulation that is mediated by the reformed stem of a ribosomal unwound RNA hairpin during elongation.",2013 Apr 29,"['Cho, Che-Pei', 'Lin, Szu-Chieh', 'Chou, Ming-Yuan', 'Hsu, Hsiu-Ting', 'Chang, Kung-Yao']",PLoS One,,,True
fa07cb83c9ec268f4be524c374659bc3584fca6f,PMC,The tree shrew provides a useful alternative model for the study of influenza H1N1 virus,http://dx.doi.org/10.1186/1743-422X-10-111,PMC3639867,23575279,CC BY,"BACKGROUND: The influenza pandemics have resulted in significant morbidity and mortality worldwide. Animal models are useful in the study of influenza virus pathogenesis. Because of various limitations in current laboratory animal models, it is essential to develop new alternative animal models for influenza virus research aimed at understanding the viral and host factors that contribute to virus infection in human. METHOD: We investigated the replicative efficiency of influenza H1N1 virus (classic strain (Influenza A/PR/8/34), seasonal influenza isolate (A/Guangzhou/GIRD/02/09) and swine-origin human influenza virus (A/Guangzhou/GIRD/07/09)) at Day1,2,4,6 and 9 p.i. using TCID(50) and qPCR assay in tree shrew model. Body temperature was monitored in the morning and evening for 3 days before infection and for 14 days. Seroconversion was detected by determining the neutralizing antibody titers against the challenge viruses in the pre- and exposure serum samples collected before infection and at 14 days p.i., respectively. Lungs and tracheas of tree shews were collected at day 14 post p.i. for histopathological analysis. Lectinhistochemistry analysis was conducted to identify the distribution of SAα2,3 Gal and SAα2,6 Gal receptors in the lung and trachea. RESULTS: The infected tree shrew displayed mild or moderate systemic and respiratory symptoms and pathological changes in respiratory tracts. The human H1N1 influenza virus may replicate in the upper respiratory tract of tree shrews. Analysis of the receptors distribution in the respiratory tract of tree shrews by lectinhistochemistry showed that sialic acid (SA)α2,6-Gal receptors were widely distributed in the trachea and nasal mucosa, whereas (SA)α2,3-Gal receptor was the main receptor in the lung tissue. CONCLUSIONS: Based on these findings, tree shrew seemed to mimic well influenza virus infection in humans. We propose that tree shrews could be a useful alternative mammalian model to study pathogenesis of influenza H1N1 virus.",2013 Apr 10,"['Yang, Zi-feng', 'Zhao, Jin', 'Zhu, Yu-tong', 'Wang, Yu-tao', 'Liu, Rong', 'Zhao, Sui-shan', 'Li, Run-feng', 'Yang, Chun-guang', 'Li, Ji-qiang', 'Zhong, Nan-shan']",Virol J,,,True
a69d1ee507dac9ef068764a5f6cec19be2fbc4a1,PMC,Baicalein Reduces Airway Injury in Allergen and IL-13 Induced Airway Inflammation,http://dx.doi.org/10.1371/journal.pone.0062916,PMC3639905,23646158,CC BY,"BACKGROUND: Baicalein, a bioflavone present in the dry roots of Scutellaria baicalensis Georgi, is known to reduce eotaxin production in human fibroblasts. However, there are no reports of its anti-asthma activity or its effect on airway injury. METHODOLOGY/PRINCIPAL FINDINGS: In a standard experimental asthma model, male Balb/c mice that were sensitized with ovalbumin (OVA), treated with baicalein (10 mg/kg, ip) or a vehicle control, either during (preventive use) or after OVA challenge (therapeutic use). In an alternate model, baicalein was administered to male Balb/c mice which were given either IL-4 or IL-13 intranasally. Features of asthma were determined by estimating airway hyperresponsiveness (AHR), histopathological changes and biochemical assays of key inflammatory molecules. Airway injury was determined with apoptotic assays, transmission electron microscopy and assessing key mitochondrial functions. Baicalein treatment reduced AHR and inflammation in both experimental models. TGF-β(1), sub-epithelial fibrosis and goblet cell metaplasia, were also reduced. Furthermore, baicalein treatment significantly reduced 12/15-LOX activity, features of mitochondrial dysfunctions, and apoptosis of bronchial epithelia. CONCLUSION/SIGNIFICANCE: Our findings demonstrate that baicalein can attenuate important features of asthma, possibly through the reduction of airway injury and restoration of mitochondrial function.",2013 Apr 30,"['Mabalirajan, Ulaganathan', 'Ahmad, Tanveer', 'Rehman, Rakhshinda', 'Leishangthem, Geeta Devi', 'Dinda, Amit Kumar', 'Agrawal, Anurag', 'Ghosh, Balaram', 'Sharma, Surendra Kumar']",PLoS One,,,True
5900930fcaa79a701a7a31a05c3fb85232f31fc6,PMC,Rosiglitazone Treatment of Type 2 Diabetic db/db Mice Attenuates Urinary Albumin and Angiotensin Converting Enzyme 2 Excretion,http://dx.doi.org/10.1371/journal.pone.0062833,PMC3639987,23646149,CC BY,"Alterations within the renal renin angiotensin system play a pivotal role in the development and progression of cardiovascular and renal disease. Angiotensin converting enzyme 2 (ACE2) is highly expressed in renal tubules and has been shown to be renoprotective in diabetes. The protease, a disintegrin and metalloprotease (ADAM) 17, is involved in the ectodomain shedding of several transmembrane proteins including ACE2. Renal ACE2 and ADAM17 were significantly increased in db/db mice compared to controls. We investigated the effect of the insulin sensitizer, rosiglitazone, on albuminuria, renal ADAM17 protein expression and ACE2 shedding in db/db diabetic mice. Rosiglitazone treatment of db/db mice normalized hyperglycemia, attenuated renal injury and decreased urinary ACE2 and renal ADAM17 protein expression. Urinary excreted ACE2 is enzymatically active. Western blot analysis of urinary ACE2 demonstrated two prominent immunoreactive bands at approximately 70 & 90 kDa. The predominant immunoreactive band is approximately 20 kDa shorter than the one demonstrated for kidney lysate, indicating possible ectodomain shedding of active renal ACE2 in the urine. Therefore, it is tempting to speculate that renoprotection of rosiglitazone could be partially mediated via downregulation of renal ADAM17 and ACE2 shedding. In addition, there was a positive correlation between blood glucose, urinary albumin, plasma glucagon, and triglyceride levels with urinary ACE2 excretion. In conclusion, urinary ACE2 could be used as a sensitive biomarker of diabetic nephropathy and for monitoring the effectiveness of renoprotective medication.",2013 Apr 30,"['Chodavarapu, Harshita', 'Grobe, Nadja', 'Somineni, Hari K.', 'Salem, Esam S. B.', 'Madhu, Malav', 'Elased, Khalid M.']",PLoS One,,,True
7150b10d52da822055fd899a9df210131bf8104e,PMC,High Human Bocavirus Viral Load Is Associated with Disease Severity in Children under Five Years of Age,http://dx.doi.org/10.1371/journal.pone.0062318,PMC3640090,23638038,CC BY,"Human bocavirus (HBoV) is a parvovirus and detected worldwide in lower respiratory tract infections (LRTIs), but its pathogenic role in respiratory illness is still debatable due to high incidence of co-infection with other respiratory viruses. To determine the prevalence of HBoV infection in patients with LRTI in Shanghai and its correlation with disease severity, we performed a 3-year prospective study of HBoV in healthy controls, outpatients and inpatients under five years of age with X-ray diagnosed LRTIs. Nasopharyngeal aspirates were tested by PCR for common respiratory viruses and by real time PCR for HBoV subtypes 1–4. Nasopharyngeal swabs from healthy controls and serum samples and stools from inpatients were also tested for HBoV1-4 by real time PCR. Viral loads were determined by quantitative real time PCR in all HBoV positive samples. HBoV1 was detected in 7.0% of inpatients, with annual rates of 5.1%, 8.0% and 4.8% in 2010, 2011 and 2012, respectively. Respiratory syncytial virus (RSV) subtype A was the most frequent co-infection detected; HBoV1 and RSVA appeared to co-circulate with similar seasonal variations. High HBoV viral loads (>10(6) copies/ml) were significantly more frequent in inpatients and outpatients than in healthy controls. There was a direct correlation of high viral load with increasing disease severity in patients co-infected with HBoV1 and at least one other respiratory virus. In summary, our data suggest that HBoV1 can cause LRTIs, but symptomatic HBoV infection is only observed in the context of high viral load.",2013 Apr 30,"['Zhao, Baihui', 'Yu, Xuelian', 'Wang, Chuanxian', 'Teng, Zheng', 'Wang, Chun', 'Shen, Jiaren', 'Gao, Ye', 'Zhu, Zhaokui', 'Wang, Jiayu', 'Yuan, Zhengan', 'Wu, Fan', 'Zhang, Xi', 'Ghildyal, Reena']",PLoS One,,,True
979d953fe8641bdfaf6479a9b479923aae95c86b,PMC,Is there a Role for Cyclophilin Inhibitors in the Management of Primary Biliary Cirrhosis?,http://dx.doi.org/10.3390/v5020423,PMC3640509,23348060,CC BY,"Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are poorly understood autoimmune liver diseases. Immunosuppression is used to treat AIH and ursodeoxycholic acid is used to slow the progression of PBC. Nevertheless, a proportion of patients with both disorders progress to liver failure. Following liver transplantation, up to a third of patients with PBC experience recurrent disease. Moreover a syndrome referred to as “de novo AIH” occurs in a proportion of patients regardless of maintenance immunosuppression, who have been transplanted for disorders unrelated to AIH. Of note, the use of cyclosporine A appears to protect against the development of recurrent PBC and de novo AIH even though it is a less potent immunosuppressive compared to tacrolimus. The reason why cyclosporine A is protective has not been determined. However, a virus resembling mouse mammary tumor virus (MMTV) has been characterized in patients with PBC and AIH. Accordingly, we hypothesized that the protective effect of cyclosporine A in liver transplant recipients may be mediated by the antiviral activity of this cyclophilin inhibitor. Treatment of the MMTV producing MM5MT cells with different antivirals and immunosuppressive agents showed that both cyclosporine A and the analogue NIM811 inhibited MMTV production from the producer cells. Herein, we discuss the evidence supporting the role of MMTV-like human betaretrovirus in the development of PBC and de novo AIH and speculate on the possibility that the agent may be associated with disease following transplantation. We also review the mechanisms of how both cyclosporine A and NIM811 may inhibit betaretrovirus production in vitro.",2013 Jan 24,"['Wasilenko, Shawn T.', 'Montano-Loza, Aldo J.', 'Mason, Andrew L.']",Viruses,,,True
0257dffb6a2cc8bdf6d252c400a38419ef256505,PMC,"Genetic Diversity of Spike, 3a, 3b and E Genes of Infectious Bronchitis Viruses and Emergence of New Recombinants in Korea",http://dx.doi.org/10.3390/v5020550,PMC3640513,23435235,CC BY,"The nucleotide sequences of a region including S1, S2, 3a, 3b and E genes of twenty-seven infectious bronchitis virus (IBV) isolates in Korea between 1990–2011 were determined and phylogenetic and computational recombination analyses were conducted. The sizes of coding regions of some genes varied among IBV isolates due to deletion or insertion of nucleotides; the nucleotide similarities of S1, S2, 3a, 3b and E genes among the 27 isolates were 75.9%–100.0%, 85%–100.0%, 64.0%–100.0%, 60.4%–100.0% and 83.1%–100.0%, respectively. According to phylogenetic analysis of S1 gene, the 27 isolates were divided into five genotypes, Mass, Korean-I (K-I), QX-like, KM91-like and New cluster 1. The phylogenetic trees based on the S2, 3a, 3b, E genes and S1-S2-3a-3b-E (S1-E) region nucleotide sequences did not closely follow the clustering based on the S1 sequence. The New cluster 1 prevalent during 2009 and 2010 was not found in 2011 but QX-like viruses became prevalent in 2011. The recombination analysis revealed two new S gene recombinants, 11036 and 11052 which might have been derived from recombinations between the New cluster 1 and QX-like viruses and between the K-I and H120 (vaccine) viruses, respectively. In conclusion, multiple IBV genotypes have co-circulated; QX-like viruses have recurred and new recombinants have emerged in Korea. This has enriched molecular epidemiology information of IBV and is useful for the control of IB in Korea.",2013 Jan 31,"['Mo, Mei-Lan', 'Hong, Seung-Min', 'Kwon, Hyuk-Joon', 'Kim, Il-Hwan', 'Song, Chang-Seon', 'Kim, Jae-Hong']",Viruses,,,True
57161303ee1012d71c8ea6ad076f2033759f897d,PMC,"Genetic Diversity of Spike, 3a, 3b and E Genes of Infectious Bronchitis Viruses and Emergence of New Recombinants in Korea",http://dx.doi.org/10.3390/v5020550,PMC3640513,23435235,CC BY,"The nucleotide sequences of a region including S1, S2, 3a, 3b and E genes of twenty-seven infectious bronchitis virus (IBV) isolates in Korea between 1990–2011 were determined and phylogenetic and computational recombination analyses were conducted. The sizes of coding regions of some genes varied among IBV isolates due to deletion or insertion of nucleotides; the nucleotide similarities of S1, S2, 3a, 3b and E genes among the 27 isolates were 75.9%–100.0%, 85%–100.0%, 64.0%–100.0%, 60.4%–100.0% and 83.1%–100.0%, respectively. According to phylogenetic analysis of S1 gene, the 27 isolates were divided into five genotypes, Mass, Korean-I (K-I), QX-like, KM91-like and New cluster 1. The phylogenetic trees based on the S2, 3a, 3b, E genes and S1-S2-3a-3b-E (S1-E) region nucleotide sequences did not closely follow the clustering based on the S1 sequence. The New cluster 1 prevalent during 2009 and 2010 was not found in 2011 but QX-like viruses became prevalent in 2011. The recombination analysis revealed two new S gene recombinants, 11036 and 11052 which might have been derived from recombinations between the New cluster 1 and QX-like viruses and between the K-I and H120 (vaccine) viruses, respectively. In conclusion, multiple IBV genotypes have co-circulated; QX-like viruses have recurred and new recombinants have emerged in Korea. This has enriched molecular epidemiology information of IBV and is useful for the control of IB in Korea.",2013 Jan 31,"['Mo, Mei-Lan', 'Hong, Seung-Min', 'Kwon, Hyuk-Joon', 'Kim, Il-Hwan', 'Song, Chang-Seon', 'Kim, Jae-Hong']",Viruses,,,False
cb56f2e5caa4992c01aedc47943146ee81cac007,PMC,Intrathecal Humoral Immunity to Encephalitic RNA Viruses,http://dx.doi.org/10.3390/v5020732,PMC3640523,23435240,CC BY,"The nervous system is the target for acute encephalitic viral infections, as well as a reservoir for persisting viruses. Intrathecal antibody (Ab) synthesis is well documented in humans afflicted by infections associated with neurological complications, as well as the demyelinating disease, multiple sclerosis. This review focuses on the origin, recruitment, maintenance, and biological relevance of Ab-secreting cells (ASC) found in the central nervous system (CNS) following experimental neurotropic RNA virus infections. We will summarize evidence for a highly dynamic, evolving humoral response characterized by temporal alterations in B cell subsets, proliferation, and differentiation. Overall local Ab plays a beneficial role via complement-independent control of virus replication, although cross or self-reactive Ab to CNS antigens may contribute to immune-mediated pathogenesis during some infections. Importantly, protective Ab exert anti-viral activity not only by direct neutralization, but also by binding to cell surface-expressed viral glycoproteins. Ab engagement of viral glycoproteins blocks budding and mediates intracellular signaling leading to restored homeostatic and innate functions. The sustained Ab production by local ASC, as well as chemokines and cytokines associated with ASC recruitment and retention, are highlighted as critical components of immune control.",2013 Feb 15,"['Phares, Timothy W.', 'Stohlman, Stephen A.', 'Bergmann, Cornelia C.']",Viruses,,,True
142a615ffb970d12beaa9597bff2b9c49da4bb96,PMC,Risk factors for severe acute lower respiratory infections in children – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.110,PMC3641871,23630139,CC BY,"AIM: To identify the risk factors in children under five years of age for severe acute lower respiratory infections (ALRI), which are the leading cause of child mortality. METHODS: We performed a systematic review of published literature available in the public domain. We conducted a quality assessment of all eligible studies according to GRADE criteria and performed a meta-analysis to report the odds ratios for all risk factors identified in these studies. RESULTS: We identified 36 studies that investigated 19 risk factors for severe ALRI. Of these, 7 risk factors were significantly associated with severe ALRI in a consistent manner across studies, with the following meta-analysis estimates of odds ratios (with 95% confidence intervals): low birth weight 3.18 (1.02-9.90), lack of exclusive breastfeeding 2.34 (1.42-3.88), crowding – more than 7 persons per household 1.96 (1.53-2.52), exposure to indoor air pollution 1.57 (1.06-2.31), incomplete immunization 1.83 (1.32-2.52), undernutrition – weight-for-age less than 2 standard deviations 4.47 (2.10-9.49), and HIV infection 4.15 (2.57-9.74). CONCLUSION: This study highlights the role of the above seven risk factors in the development of severe pneumonia in under-five children. In addition, it emphasizes the need for further studies investigating other potential risk factors. Since these risk factors are potentially preventable, health policies targeted at reducing their prevalence provide a basis for decreasing the burden of childhood pneumonia.",2013 Apr,"['Jackson, Stewart', 'Mathews, Kyle H.', 'Pulanić, Dražen', 'Falconer, Rachel', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,True
6aedd9fc4bea8ecfcbea50546a50431a6ebfce67,PMC,Risk factors for severe acute lower respiratory infections in children – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.110,PMC3641871,23630139,CC BY,"AIM: To identify the risk factors in children under five years of age for severe acute lower respiratory infections (ALRI), which are the leading cause of child mortality. METHODS: We performed a systematic review of published literature available in the public domain. We conducted a quality assessment of all eligible studies according to GRADE criteria and performed a meta-analysis to report the odds ratios for all risk factors identified in these studies. RESULTS: We identified 36 studies that investigated 19 risk factors for severe ALRI. Of these, 7 risk factors were significantly associated with severe ALRI in a consistent manner across studies, with the following meta-analysis estimates of odds ratios (with 95% confidence intervals): low birth weight 3.18 (1.02-9.90), lack of exclusive breastfeeding 2.34 (1.42-3.88), crowding – more than 7 persons per household 1.96 (1.53-2.52), exposure to indoor air pollution 1.57 (1.06-2.31), incomplete immunization 1.83 (1.32-2.52), undernutrition – weight-for-age less than 2 standard deviations 4.47 (2.10-9.49), and HIV infection 4.15 (2.57-9.74). CONCLUSION: This study highlights the role of the above seven risk factors in the development of severe pneumonia in under-five children. In addition, it emphasizes the need for further studies investigating other potential risk factors. Since these risk factors are potentially preventable, health policies targeted at reducing their prevalence provide a basis for decreasing the burden of childhood pneumonia.",2013 Apr,"['Jackson, Stewart', 'Mathews, Kyle H.', 'Pulanić, Dražen', 'Falconer, Rachel', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,False
f3adb474ad03cc606ada08752245a6cc86aaaaa1,PMC,Risk factors for severe acute lower respiratory infections in children – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.110,PMC3641871,23630139,CC BY,"AIM: To identify the risk factors in children under five years of age for severe acute lower respiratory infections (ALRI), which are the leading cause of child mortality. METHODS: We performed a systematic review of published literature available in the public domain. We conducted a quality assessment of all eligible studies according to GRADE criteria and performed a meta-analysis to report the odds ratios for all risk factors identified in these studies. RESULTS: We identified 36 studies that investigated 19 risk factors for severe ALRI. Of these, 7 risk factors were significantly associated with severe ALRI in a consistent manner across studies, with the following meta-analysis estimates of odds ratios (with 95% confidence intervals): low birth weight 3.18 (1.02-9.90), lack of exclusive breastfeeding 2.34 (1.42-3.88), crowding – more than 7 persons per household 1.96 (1.53-2.52), exposure to indoor air pollution 1.57 (1.06-2.31), incomplete immunization 1.83 (1.32-2.52), undernutrition – weight-for-age less than 2 standard deviations 4.47 (2.10-9.49), and HIV infection 4.15 (2.57-9.74). CONCLUSION: This study highlights the role of the above seven risk factors in the development of severe pneumonia in under-five children. In addition, it emphasizes the need for further studies investigating other potential risk factors. Since these risk factors are potentially preventable, health policies targeted at reducing their prevalence provide a basis for decreasing the burden of childhood pneumonia.",2013 Apr,"['Jackson, Stewart', 'Mathews, Kyle H.', 'Pulanić, Dražen', 'Falconer, Rachel', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,False
f0a8aaaee772b9a00fcddc3d82448ec5b71c2d03,PMC,Risk factors for severe acute lower respiratory infections in children – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.110,PMC3641871,23630139,CC BY,"AIM: To identify the risk factors in children under five years of age for severe acute lower respiratory infections (ALRI), which are the leading cause of child mortality. METHODS: We performed a systematic review of published literature available in the public domain. We conducted a quality assessment of all eligible studies according to GRADE criteria and performed a meta-analysis to report the odds ratios for all risk factors identified in these studies. RESULTS: We identified 36 studies that investigated 19 risk factors for severe ALRI. Of these, 7 risk factors were significantly associated with severe ALRI in a consistent manner across studies, with the following meta-analysis estimates of odds ratios (with 95% confidence intervals): low birth weight 3.18 (1.02-9.90), lack of exclusive breastfeeding 2.34 (1.42-3.88), crowding – more than 7 persons per household 1.96 (1.53-2.52), exposure to indoor air pollution 1.57 (1.06-2.31), incomplete immunization 1.83 (1.32-2.52), undernutrition – weight-for-age less than 2 standard deviations 4.47 (2.10-9.49), and HIV infection 4.15 (2.57-9.74). CONCLUSION: This study highlights the role of the above seven risk factors in the development of severe pneumonia in under-five children. In addition, it emphasizes the need for further studies investigating other potential risk factors. Since these risk factors are potentially preventable, health policies targeted at reducing their prevalence provide a basis for decreasing the burden of childhood pneumonia.",2013 Apr,"['Jackson, Stewart', 'Mathews, Kyle H.', 'Pulanić, Dražen', 'Falconer, Rachel', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,False
bb155121c9a40b8b3dbb5fa669e2686d68bb31df,PMC,Risk factors for severe acute lower respiratory infections in children – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.110,PMC3641871,23630139,CC BY,"AIM: To identify the risk factors in children under five years of age for severe acute lower respiratory infections (ALRI), which are the leading cause of child mortality. METHODS: We performed a systematic review of published literature available in the public domain. We conducted a quality assessment of all eligible studies according to GRADE criteria and performed a meta-analysis to report the odds ratios for all risk factors identified in these studies. RESULTS: We identified 36 studies that investigated 19 risk factors for severe ALRI. Of these, 7 risk factors were significantly associated with severe ALRI in a consistent manner across studies, with the following meta-analysis estimates of odds ratios (with 95% confidence intervals): low birth weight 3.18 (1.02-9.90), lack of exclusive breastfeeding 2.34 (1.42-3.88), crowding – more than 7 persons per household 1.96 (1.53-2.52), exposure to indoor air pollution 1.57 (1.06-2.31), incomplete immunization 1.83 (1.32-2.52), undernutrition – weight-for-age less than 2 standard deviations 4.47 (2.10-9.49), and HIV infection 4.15 (2.57-9.74). CONCLUSION: This study highlights the role of the above seven risk factors in the development of severe pneumonia in under-five children. In addition, it emphasizes the need for further studies investigating other potential risk factors. Since these risk factors are potentially preventable, health policies targeted at reducing their prevalence provide a basis for decreasing the burden of childhood pneumonia.",2013 Apr,"['Jackson, Stewart', 'Mathews, Kyle H.', 'Pulanić, Dražen', 'Falconer, Rachel', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,False
428d1091cf63872ea81cb3c1632d76c4813748a1,PMC,Viral etiology of hospitalized acute lower respiratory infections in children under 5 years of age – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.122,PMC3641872,23630140,CC BY,"AIM: To estimate the proportional contribution of influenza viruses (IV), parainfluenza viruses (PIV), adenoviruses (AV), and coronaviruses (CV) to the burden of severe acute lower respiratory infections (ALRI). METHODS: The review of the literature followed PRISMA guidelines. We included studies of hospitalized children aged 0-4 years with confirmed ALRI published between 1995 and 2011. A total of 51 studies were included in the final review, comprising 56 091 hospitalized ALRI episodes. RESULTS: IV was detected in 3.0% (2.2%-4.0%) of all hospitalized ALRI cases, PIV in 2.7% (1.9%-3.7%), and AV in 5.8% (3.4%-9.1%). CV are technically difficult to culture, and they were detected in 4.8% of all hospitalized ALRI patients in one study. When respiratory syncytial virus (RSV) and less common viruses were included, at least one virus was detected in 50.4% (40.0%-60.7%) of all hospitalized severe ALRI episodes. Moreover, 21.9% (17.7%-26.4%) of these viral ALRI were mixed, including more than one viral pathogen. Among all severe ALRI with confirmed viral etiology, IV accounted for 7.0% (5.5%-8.7%), PIV for 5.8% (4.1%-7.7%), and AV for 8.8% (5.3%-13.0%). CV was found in 10.6% of virus-positive pneumonia patients in one study. CONCLUSIONS: This article provides the most comprehensive analysis of the contribution of four viral causes to severe ALRI to date. Our results can be used in further cost-effectiveness analyses of vaccine development and implementation for a number of respiratory viruses.",2013 Apr,"['Lukšić, Ivana', 'Kearns, Patrick K', 'Scott, Fiona', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,True
82441199a6d3222ad51244e351b5df2d53aecc0f,PMC,Viral etiology of hospitalized acute lower respiratory infections in children under 5 years of age – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.122,PMC3641872,23630140,CC BY,"AIM: To estimate the proportional contribution of influenza viruses (IV), parainfluenza viruses (PIV), adenoviruses (AV), and coronaviruses (CV) to the burden of severe acute lower respiratory infections (ALRI). METHODS: The review of the literature followed PRISMA guidelines. We included studies of hospitalized children aged 0-4 years with confirmed ALRI published between 1995 and 2011. A total of 51 studies were included in the final review, comprising 56 091 hospitalized ALRI episodes. RESULTS: IV was detected in 3.0% (2.2%-4.0%) of all hospitalized ALRI cases, PIV in 2.7% (1.9%-3.7%), and AV in 5.8% (3.4%-9.1%). CV are technically difficult to culture, and they were detected in 4.8% of all hospitalized ALRI patients in one study. When respiratory syncytial virus (RSV) and less common viruses were included, at least one virus was detected in 50.4% (40.0%-60.7%) of all hospitalized severe ALRI episodes. Moreover, 21.9% (17.7%-26.4%) of these viral ALRI were mixed, including more than one viral pathogen. Among all severe ALRI with confirmed viral etiology, IV accounted for 7.0% (5.5%-8.7%), PIV for 5.8% (4.1%-7.7%), and AV for 8.8% (5.3%-13.0%). CV was found in 10.6% of virus-positive pneumonia patients in one study. CONCLUSIONS: This article provides the most comprehensive analysis of the contribution of four viral causes to severe ALRI to date. Our results can be used in further cost-effectiveness analyses of vaccine development and implementation for a number of respiratory viruses.",2013 Apr,"['Lukšić, Ivana', 'Kearns, Patrick K', 'Scott, Fiona', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,True
1d2268701960bba63d687cc67c9f1864ab05cd00,PMC,Viral etiology of hospitalized acute lower respiratory infections in children under 5 years of age – a systematic review and meta-analysis,http://dx.doi.org/10.3325/cmj.2013.54.122,PMC3641872,23630140,CC BY,"AIM: To estimate the proportional contribution of influenza viruses (IV), parainfluenza viruses (PIV), adenoviruses (AV), and coronaviruses (CV) to the burden of severe acute lower respiratory infections (ALRI). METHODS: The review of the literature followed PRISMA guidelines. We included studies of hospitalized children aged 0-4 years with confirmed ALRI published between 1995 and 2011. A total of 51 studies were included in the final review, comprising 56 091 hospitalized ALRI episodes. RESULTS: IV was detected in 3.0% (2.2%-4.0%) of all hospitalized ALRI cases, PIV in 2.7% (1.9%-3.7%), and AV in 5.8% (3.4%-9.1%). CV are technically difficult to culture, and they were detected in 4.8% of all hospitalized ALRI patients in one study. When respiratory syncytial virus (RSV) and less common viruses were included, at least one virus was detected in 50.4% (40.0%-60.7%) of all hospitalized severe ALRI episodes. Moreover, 21.9% (17.7%-26.4%) of these viral ALRI were mixed, including more than one viral pathogen. Among all severe ALRI with confirmed viral etiology, IV accounted for 7.0% (5.5%-8.7%), PIV for 5.8% (4.1%-7.7%), and AV for 8.8% (5.3%-13.0%). CV was found in 10.6% of virus-positive pneumonia patients in one study. CONCLUSIONS: This article provides the most comprehensive analysis of the contribution of four viral causes to severe ALRI to date. Our results can be used in further cost-effectiveness analyses of vaccine development and implementation for a number of respiratory viruses.",2013 Apr,"['Lukšić, Ivana', 'Kearns, Patrick K', 'Scott, Fiona', 'Rudan, Igor', 'Campbell, Harry', 'Nair, Harish']",Croat Med J,,,False
ac379a37c74e9e9ea13ad9813f46f53dbab62b66,PMC,A geographic analysis of population density thresholds in the influenza pandemic of 1918–19,http://dx.doi.org/10.1186/1476-072X-12-9,PMC3641965,23425498,CC BY,"BACKGROUND: Geographic variables play an important role in the study of epidemics. The role of one such variable, population density, in the spread of influenza is controversial. Prior studies have tested for such a role using arbitrary thresholds for population density above or below which places are hypothesized to have higher or lower mortality. The results of such studies are mixed. The objective of this study is to estimate, rather than assume, a threshold level of population density that separates low-density regions from high-density regions on the basis of population loss during an influenza pandemic. We study the case of the influenza pandemic of 1918–19 in India, where over 15 million people died in the short span of less than one year. METHODS: Using data from six censuses for 199 districts of India (n=1194), the country with the largest number of deaths from the influenza of 1918–19, we use a sample-splitting method embedded within a population growth model that explicitly quantifies population loss from the pandemic to estimate a threshold level of population density that separates low-density districts from high-density districts. RESULTS: The results demonstrate a threshold level of population density of 175 people per square mile. A concurrent finding is that districts on the low side of the threshold experienced rates of population loss (3.72%) that were lower than districts on the high side of the threshold (4.69%). CONCLUSIONS: This paper introduces a useful analytic tool to the health geographic literature. It illustrates an application of the tool to demonstrate that it can be useful for pandemic awareness and preparedness efforts. Specifically, it estimates a level of population density above which policies to socially distance, redistribute or quarantine populations are likely to be more effective than they are for areas with population densities that lie below the threshold.",2013 Feb 20,"['Chandra, Siddharth', 'Kassens-Noor, Eva', 'Kuljanin, Goran', 'Vertalka, Joshua']",Int J Health Geogr,,,True
104905bcc37d4afad386adaeed57fbe4fc73a595,PMC,Inference of R (0) and Transmission Heterogeneity from the Size Distribution of Stuttering Chains,http://dx.doi.org/10.1371/journal.pcbi.1002993,PMC3642075,23658504,CC0,"For many infectious disease processes such as emerging zoonoses and vaccine-preventable diseases, [Image: see text] and infections occur as self-limited stuttering transmission chains. A mechanistic understanding of transmission is essential for characterizing the risk of emerging diseases and monitoring spatio-temporal dynamics. Thus methods for inferring [Image: see text] and the degree of heterogeneity in transmission from stuttering chain data have important applications in disease surveillance and management. Previous researchers have used chain size distributions to infer [Image: see text], but estimation of the degree of individual-level variation in infectiousness (as quantified by the dispersion parameter, [Image: see text]) has typically required contact tracing data. Utilizing branching process theory along with a negative binomial offspring distribution, we demonstrate how maximum likelihood estimation can be applied to chain size data to infer both [Image: see text] and the dispersion parameter that characterizes heterogeneity. While the maximum likelihood value for [Image: see text] is a simple function of the average chain size, the associated confidence intervals are dependent on the inferred degree of transmission heterogeneity. As demonstrated for monkeypox data from the Democratic Republic of Congo, this impacts when a statistically significant change in [Image: see text] is detectable. In addition, by allowing for superspreading events, inference of [Image: see text] shifts the threshold above which a transmission chain should be considered anomalously large for a given value of [Image: see text] (thus reducing the probability of false alarms about pathogen adaptation). Our analysis of monkeypox also clarifies the various ways that imperfect observation can impact inference of transmission parameters, and highlights the need to quantitatively evaluate whether observation is likely to significantly bias results.",2013 May 2,"['Blumberg, Seth', 'Lloyd-Smith, James O.']",PLoS Comput Biol,,,True
80117863dd2a5d88ad1c777af6952bd136811a25,PMC,Inference of R (0) and Transmission Heterogeneity from the Size Distribution of Stuttering Chains,http://dx.doi.org/10.1371/journal.pcbi.1002993,PMC3642075,23658504,CC0,"For many infectious disease processes such as emerging zoonoses and vaccine-preventable diseases, [Image: see text] and infections occur as self-limited stuttering transmission chains. A mechanistic understanding of transmission is essential for characterizing the risk of emerging diseases and monitoring spatio-temporal dynamics. Thus methods for inferring [Image: see text] and the degree of heterogeneity in transmission from stuttering chain data have important applications in disease surveillance and management. Previous researchers have used chain size distributions to infer [Image: see text], but estimation of the degree of individual-level variation in infectiousness (as quantified by the dispersion parameter, [Image: see text]) has typically required contact tracing data. Utilizing branching process theory along with a negative binomial offspring distribution, we demonstrate how maximum likelihood estimation can be applied to chain size data to infer both [Image: see text] and the dispersion parameter that characterizes heterogeneity. While the maximum likelihood value for [Image: see text] is a simple function of the average chain size, the associated confidence intervals are dependent on the inferred degree of transmission heterogeneity. As demonstrated for monkeypox data from the Democratic Republic of Congo, this impacts when a statistically significant change in [Image: see text] is detectable. In addition, by allowing for superspreading events, inference of [Image: see text] shifts the threshold above which a transmission chain should be considered anomalously large for a given value of [Image: see text] (thus reducing the probability of false alarms about pathogen adaptation). Our analysis of monkeypox also clarifies the various ways that imperfect observation can impact inference of transmission parameters, and highlights the need to quantitatively evaluate whether observation is likely to significantly bias results.",2013 May 2,"['Blumberg, Seth', 'Lloyd-Smith, James O.']",PLoS Comput Biol,,,False
7e0a164300efd5ab4d734ae591fcd8b4ef3554f8,PMC,Inference of R (0) and Transmission Heterogeneity from the Size Distribution of Stuttering Chains,http://dx.doi.org/10.1371/journal.pcbi.1002993,PMC3642075,23658504,CC0,"For many infectious disease processes such as emerging zoonoses and vaccine-preventable diseases, [Image: see text] and infections occur as self-limited stuttering transmission chains. A mechanistic understanding of transmission is essential for characterizing the risk of emerging diseases and monitoring spatio-temporal dynamics. Thus methods for inferring [Image: see text] and the degree of heterogeneity in transmission from stuttering chain data have important applications in disease surveillance and management. Previous researchers have used chain size distributions to infer [Image: see text], but estimation of the degree of individual-level variation in infectiousness (as quantified by the dispersion parameter, [Image: see text]) has typically required contact tracing data. Utilizing branching process theory along with a negative binomial offspring distribution, we demonstrate how maximum likelihood estimation can be applied to chain size data to infer both [Image: see text] and the dispersion parameter that characterizes heterogeneity. While the maximum likelihood value for [Image: see text] is a simple function of the average chain size, the associated confidence intervals are dependent on the inferred degree of transmission heterogeneity. As demonstrated for monkeypox data from the Democratic Republic of Congo, this impacts when a statistically significant change in [Image: see text] is detectable. In addition, by allowing for superspreading events, inference of [Image: see text] shifts the threshold above which a transmission chain should be considered anomalously large for a given value of [Image: see text] (thus reducing the probability of false alarms about pathogen adaptation). Our analysis of monkeypox also clarifies the various ways that imperfect observation can impact inference of transmission parameters, and highlights the need to quantitatively evaluate whether observation is likely to significantly bias results.",2013 May 2,"['Blumberg, Seth', 'Lloyd-Smith, James O.']",PLoS Comput Biol,,,False
792417a1bbb50a19ce96e8354aa9f16f2424b850,PMC,High incidence of respiratory viruses in critically ill adult patients with respiratory failure,http://dx.doi.org/10.1186/cc12073,PMC3642395,,CC BY,,2013 Mar 19,"['Sietses, M', 'Faber, TE', 'Bont, L', 'Buter, H', 'Boerma, EC']",Crit Care,,,True
29e75f8938836f57cbdfa2e73f05939ee5f561a1,PMC,A Comparison of the Clinical and Epidemiological Characteristics of Adult Patients with Laboratory-Confirmed Influenza A or B during the 2011–2012 Influenza Season in Korea: A Multi-Center Study,http://dx.doi.org/10.1371/journal.pone.0062685,PMC3643978,23671624,CC BY,"BACKGROUND: During the 2011/2012 winter influenza season in the Republic of Korea, influenza A (H3N2) was the predominant virus in the first peak period of influenza activity during the second half of January 2012. On the other hand, influenza B was the predominant virus in the second peak period of influenza activity during the second half of March 2012. The objectives of this study were to compare the clinical and epidemiological characteristics of patients with laboratory-confirmed influenza A or influenza B. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed data from 2,129 adult patients with influenza-like illnesses who visited the emergency rooms of seven university hospitals in Korea from October 2011 to May 2012. Of 850 patients with laboratory-confirmed influenza, 656 (77.2%) had influenza A (H3N2), and 194 (22.8%) influenza B. Age, and the frequencies of cardiovascular disorders, diabetes, hypertension were significantly higher in patients with influenza A (H3N2) (P<0.05). The frequencies of leukopenia or thrombocytopenia in patients with influenza B at initial presentation were statistically higher than those in patients with influenza A (H3N2) (P<0.05). The rate of hospitalization, and length of hospital stay were statistically higher in patients with influenza A (H3N2) (P<0.05), and of the 79 hospitalized patients, the frequency of diabetes, hypertension, cases having at least one of the comorbid conditions, and the proportion of elderly were significantly higher in patients with influenza A (H3N2) (P<0.05). CONCLUSIONS: The proportion of males to females and elderly population were significantly higher for influenza A (H3N2) patients group compared with influenza B group. Hypertension, diabetes, chronic lung diseases, cardiovascular disorders, and neuromuscular diseases were independently associated with hospitalization due to influenza. Physicians should assess and treat the underlying comorbid conditions as well as influenza viral infections for the appropriate management of patients with influenza.",2013 May 3,"['Wie, Seong-Heon', 'So, Byung Hak', 'Song, Joon Young', 'Cheong, Hee Jin', 'Seo, Yu Bin', 'Choi, Sung Hyuk', 'Noh, Ji Yun', 'Baek, Ji Hyeon', 'Lee, Jin Soo', 'Kim, Hyo Youl', 'Kim, Young Keun', 'Choi, Won Suk', 'Lee, Jacob', 'Jeong, Hye Won', 'Kim, Woo Joo']",PLoS One,,,True
bc7c67f8bf777ec11fcdfdbd36ed0c3fb55f2c72,PMC,Age-specific contacts and travel patterns in the spatial spread of 2009 H1N1 influenza pandemic,http://dx.doi.org/10.1186/1471-2334-13-176,PMC3644502,23587010,CC BY,"BACKGROUND: Confirmed H1N1 cases during late spring and summer 2009 in various countries showed a substantial age shift between importations and local transmission cases, with adults mainly responsible for seeding unaffected regions and children most frequently driving community outbreaks. METHODS: We introduce a multi-host stochastic metapopulation model with two age classes to analytically investigate the role of a heterogeneously mixing population and its associated non-homogeneous travel behaviors on the risk of a major epidemic. We inform the model with demographic data, contact data and travel statistics of Europe and Mexico, and calibrate it to the 2009 H1N1 pandemic early outbreak. We allow for variations of the model parameters to explore the conditions of invasion under different scenarios. RESULTS: We derive the expression for the potential of global invasion of the epidemic that depends on the transmissibility of the pathogen, the transportation network and mobility features, the demographic profile and the mixing pattern. Higher assortativity in the contact pattern greatly increases the probability of spatial containment of the epidemic, this effect being contrasted by an increase in the social activity of adults vs. children. Heterogeneous features of the mobility network characterizing its topology and traffic flows strongly favor the invasion of the pathogen at the spatial level, as also a larger fraction of children traveling. Variations in the demographic profile and mixing habits across countries lead to heterogeneous outbreak situations. Model results are compatible with the H1N1 spatial transmission dynamics observed. CONCLUSIONS: This work illustrates the importance of considering age-dependent mixing profiles and mobility features coupled together to study the conditions for the spatial invasion of an emerging influenza pandemic. Its results allow the immediate assessment of the risk of a major epidemic for a specific scenario upon availability of data, and the evaluation of the potential effectiveness of public health interventions targeting specific age groups, their interactions and mobility behaviors. The approach provides a general modeling framework that can be used for other types of partitions of the host population and applied to different settings.",2013 Apr 15,"['Apolloni, Andrea', 'Poletto, Chiara', 'Colizza, Vittoria']",BMC Infect Dis,,,True
1c3e28d4bd170a986bb5566cb9f9616410f67763,PMC,Age-specific contacts and travel patterns in the spatial spread of 2009 H1N1 influenza pandemic,http://dx.doi.org/10.1186/1471-2334-13-176,PMC3644502,23587010,CC BY,"BACKGROUND: Confirmed H1N1 cases during late spring and summer 2009 in various countries showed a substantial age shift between importations and local transmission cases, with adults mainly responsible for seeding unaffected regions and children most frequently driving community outbreaks. METHODS: We introduce a multi-host stochastic metapopulation model with two age classes to analytically investigate the role of a heterogeneously mixing population and its associated non-homogeneous travel behaviors on the risk of a major epidemic. We inform the model with demographic data, contact data and travel statistics of Europe and Mexico, and calibrate it to the 2009 H1N1 pandemic early outbreak. We allow for variations of the model parameters to explore the conditions of invasion under different scenarios. RESULTS: We derive the expression for the potential of global invasion of the epidemic that depends on the transmissibility of the pathogen, the transportation network and mobility features, the demographic profile and the mixing pattern. Higher assortativity in the contact pattern greatly increases the probability of spatial containment of the epidemic, this effect being contrasted by an increase in the social activity of adults vs. children. Heterogeneous features of the mobility network characterizing its topology and traffic flows strongly favor the invasion of the pathogen at the spatial level, as also a larger fraction of children traveling. Variations in the demographic profile and mixing habits across countries lead to heterogeneous outbreak situations. Model results are compatible with the H1N1 spatial transmission dynamics observed. CONCLUSIONS: This work illustrates the importance of considering age-dependent mixing profiles and mobility features coupled together to study the conditions for the spatial invasion of an emerging influenza pandemic. Its results allow the immediate assessment of the risk of a major epidemic for a specific scenario upon availability of data, and the evaluation of the potential effectiveness of public health interventions targeting specific age groups, their interactions and mobility behaviors. The approach provides a general modeling framework that can be used for other types of partitions of the host population and applied to different settings.",2013 Apr 15,"['Apolloni, Andrea', 'Poletto, Chiara', 'Colizza, Vittoria']",BMC Infect Dis,,,True
137b25ee1545c4b01332709ab1e24dcf935d6f96,PMC,A Role for Protein Phosphatase 2A in Regulating p38 Mitogen Activated Protein Kinase Activation and Tumor Necrosis Factor-Alpha Expression during Influenza Virus Infection,http://dx.doi.org/10.3390/ijms14047327,PMC3645688,23549267,CC BY,"Influenza viruses of avian origin continue to pose pandemic threats to human health. Some of the H5N1 and H9N2 virus subtypes induce markedly elevated cytokine levels when compared with the seasonal H1N1 virus. We previously showed that H5N1/97 hyperinduces tumor necrosis factor (TNF)-alpha through p38 mitogen activated protein kinase (MAPK). However, the detailed mechanisms of p38MAPK activation and TNF-alpha hyperinduction following influenza virus infections are not known. Negative feedback regulations of cytokine expression play important roles in avoiding overwhelming production of proinflammatory cytokines. Here we hypothesize that protein phosphatases are involved in the regulation of cytokine expressions during influenza virus infection. We investigated the roles of protein phosphatases including MAPK phosphatase-1 (MKP-1) and protein phosphatase type 2A (PP2A) in modulating p38MAPK activation and downstream TNF-alpha expressions in primary human monocyte-derived macrophages (PBMac) infected with H9N2/G1 or H1N1 influenza virus. We demonstrate that H9N2/G1 virus activated p38MAPK and hyperinduced TNF-alpha production in PBMac when compared with H1N1 virus. H9N2/G1 induced PP2A activity in PBMac and, with the treatment of a PP2A inhibitor, p38MAPK phosphorylation and TNF-alpha production were further increased in the virus-infected macrophages. However, H9N2/G1 did not induce the expression of PP2A indicating that the activation of PP2A is not mediated by p38MAPK in virus-infected PBMac. On the other hand, PP2A may not be the targets of H9N2/G1 in the upstream of p38MAPK signaling pathways since H1N1 also induced PP2A activation in primary macrophages. Our results may provide new insights into the control of cytokine dysregulation.",2013 Apr 2,"['Law, Anna H. Y.', 'Tam, Alex H. M.', 'Lee, Davy C. W.', 'Lau, Allan S. Y.']",Int J Mol Sci,,,True
67ef4b8a1eaaf14328ad66f28e0f103c608e73d4,PMC,Identifying Early Inflammatory Changes in Monocyte-Derived Macrophages from a Population with IQ-Discrepant Episodic Memory,http://dx.doi.org/10.1371/journal.pone.0063194,PMC3646027,23671673,CC BY,"BACKGROUND: Cells of the innate immune system including monocytes and macrophages are the first line of defence against infections and are critical regulators of the inflammatory response. These cells express toll-like receptors (TLRs), innate immune receptors which govern tailored inflammatory gene expression patterns. Monocytes, which produce pro-inflammatory mediators, are readily recruited to the central nervous system (CNS) in neurodegenerative diseases. METHODS: This study explored the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) isolated from healthy elderly adults who we classified as either IQ memory-consistent (high-performing, HP) or IQ memory-discrepant (low-performing, LP). RESULTS: The expression of CD11b, TLR4 and TLR2 was increased in MDMs from the LP group when compared to HP cohort. MDMs from both groups responded robustly to treatment with the TLR4 activator, lipopolysaccharide (LPS), in terms of cytokine production. Significantly, MDMs from the LP group displayed hypersensitivity to LPS exposure. INTERPRETATION: Overall these findings define differential receptor expression and cytokine profiles that occur in MDMs derived from a cohort of IQ memory-discrepant individuals. These changes are indicative of inflammation and may be involved in the prodromal processes leading to the development of neurodegenerative disease.",2013 May 6,"['Downer, Eric J.', 'Jones, Raasay S.', 'McDonald, Claire L.', 'Greco, Eleonora', 'Brennan, Sabina', 'Connor, Thomas J.', 'Robertson, Ian H.', 'Lynch, Marina A.']",PLoS One,,,True
a58e2554025589270e688199f55c97c719fe874d,PMC,Reinvigorating the Role of Science in Democracy,http://dx.doi.org/10.1371/journal.pbio.1001553,PMC3646724,23667322,CC BY,"Private and political interests routinely conspire to sideline and misrepresent science and evidence in the public policy process. The Center for Science and Democracy, a new initiative at the Union of Concerned Scientists, endeavors to change this dynamic to strengthen the role of science in decision making.",2013 May 7,"['Rosenberg, Andrew A.', 'Halpern, Michael', 'Shulman, Seth', 'Wexler, Celia', 'Phartiyal, Pallavi']",PLoS Biol,,,True
5c78286b1684b83d68551054909958005fc2529a,PMC,The Transient Nature of Bunyamwera Orthobunyavirus NSs Protein Expression: Effects of Increased Stability of NSs Protein on Virus Replication,http://dx.doi.org/10.1371/journal.pone.0064137,PMC3648540,23667701,CC BY,"The NSs proteins of bunyaviruses are the viral interferon antagonists, counteracting the host's antiviral response to infection. During high-multiplicity infection of cultured mammalian cells with Bunyamwera orthobunyavirus (BUNV), NSs is rapidly degraded after reaching peak levels of expression at 12hpi. Through the use of inhibitors this was shown to be the result of proteasomal degradation. A recombinant virus (rBUN4KR), in which all four lysine residues in NSs were replaced by arginine residues, expresses an NSs protein (NSs4KR) that is resistant to degradation, confirming that degradation is lysine-dependent. However, despite repeated attempts, no direct ubiquitylation of NSs in infected cells could be demonstrated. This suggests that degradation of NSs, although lysine-dependent, may be achieved through an indirect mechanism. Infection of cultured mammalian cells or mice indicated no disadvantage for the virus in having a non-degradable NSs protein: in fact rBUN4KR had a slight growth advantage over wtBUNV in interferon-competent cells, presumably due to the increased and prolonged presence of NSs. In cultured mosquito cells there was no difference in growth between wild-type BUNV and rBUN4KR, but surprisingly NSs4KR was not stabilised compared to the wild-type NSs protein.",2013 May 8,"['van Knippenberg, Ingeborg', 'Fragkoudis, Rennos', 'Elliott, Richard M.']",PLoS One,,,True
10c5b88204b337e7d05aceba5fc73d041153d0d3,PMC,"Viral Aetiology in Adults with Acute Upper Respiratory Tract Infection in Jinan, Northern China",http://dx.doi.org/10.1155/2013/869521,PMC3649347,23690828,CC BY,"Our study investigated the epidemiology of respiratory viruses in adult patients with upper respiratory tract infection (URTI) between August 2009 and September 2010 in Jinan, northern China. Nasal and throat swabs (n = 596) were collected from adult patients with URTIs. Nine respiratory-related viruses, including IFV, PIV, HRV, HMPV, HBoV, HCoV, ADV, RSV, and EV, were detected in all samples by conventional and reverse transcription polymerase chain reactions. Positive detection rate for respiratory virus was 38.76% and codetection rate was 4.70% in adults with acute respiratory tract infections. IFV (20.81%) was the dominant agent detected and IFVB had a higher incidence (12.58%) than IFVA (7.72%). Detection rates of 8.22%, 5.03%, 3.69%, and 2.52% were observed for HBoV, HRV, EV, and RSV, respectively. HCoV had the lowest detection rate of 0.50%. HBoV, HRV, EV, and ADV infection rates were higher in the 14–25-year-old group than in the 26–65-year-old group. Codetection rates were higher (7.52%) in the 14–25-year-old group than in the older age group (2.64%). The spectrum of respiratory virus infection in adult patients with URTIs was different in Jinan compared with other cities in China.",2013 Apr 15,"['Lu, Yanqin', 'Tong, Jiabei', 'Pei, Fengyan', 'Yang, Yanping', 'Xu, Dong', 'Ji, Mingyu', 'Xing, Chunyan', 'Jia, Pingdong', 'Xu, Chao', 'Wang, Yunshan', 'Li, Gongchao', 'Chai, Zhenbin', 'Liu, Yan', 'Han, Jinxiang']",Clin Dev Immunol,,,True
d392fcba605d12d5f9b3b31f6d0c620b6a89cdcc,PMC,Curcumin Nanoparticles Ameliorate ICAM-1 Expression in TNF-α-Treated Lung Epithelial Cells through p47 (phox) and MAPKs/AP-1 Pathways,http://dx.doi.org/10.1371/journal.pone.0063845,PMC3650060,23671702,CC BY,"Upregulation of intercellular adhesion molecule-1 (ICAM-1) involves adhesions between both circulating and resident leukocytes and the human lung epithelial cells during lung inflammatory reactions. We have previously demonstrated that curcumin-loaded polyvinylpyrrolidone nanoparticles (CURN) improve the anti-inflammatory and anti-oxidative properties of curcumin in hepatocytes. In this study, we focused on the effects of CURN on the expression of ICAM-1 in TNF-α-treated lung epithelial cells and compared these to the effects of curcumin water preparation (CURH). TNF-αinduced ICAM-1 expression, ROS production, and cell-cell adhesion were significantly attenuated by the pretreatment with antioxidants (DPI, APO, or NAC) and CURN, but not by CURH, as revealed by western blot analysis, RT-PCR, promoter assay, and ROS detection and adhesion assay. In addition, treatment of TNF-α-treated cells with CURN and antioxidants also resulted in an inhibition of activation of p47 (phox) and phosphorylation of MAPKs, as compared to that using CURH. Our findings also suggest that phosphorylation of MAPKs may eventually lead to the activation of transcription factors. We also observed that the effects of TNF-α treatment for 30 min, which includes a significant increase in the binding activity of AP-1 and phosphorylation of c-jun and c-fos genes, were reduced by CURN treatment. In vivo studies have revealed that CURN improved the anti-inflammation activities of CURH in the lung epithelial cells of TNF-α-treated mice. Our results indicate that curcumin-loaded polyvinylpyrrolidone nanoparticles may potentially serve as an anti-inflammatory drug for the treatment of respiratory diseases.",2013 May 9,"['Yen, Feng-Lin', 'Tsai, Ming-Horng', 'Yang, Chuen-Mao', 'Liang, Chan-Jung', 'Lin, Chun-Ching', 'Chiang, Yao-Chang', 'Lee, Hui-Chun', 'Ko, Horng-Huey', 'Lee, Chiang-Wen']",PLoS One,,,True
1536008edcc909523ffc39c62b8389ba0ee76f95,PMC,Pediatric Asthma Mortality and Hospitalization Trends Across Asia Pacific Relationship With Asthma Drug Utilization Patterns,http://dx.doi.org/10.1097/WOX.0b013e3181a7c288,PMC3651014,23283014,CC BY,"BACKGROUND: The wide variability in prevalence of childhood asthma across Asia Pacific is well documented, but less is known about its trends in mortality and hospitalization. OBJECTIVES: To examine pediatric asthma mortality and hospitalization trends of selected countries across Asia Pacific, and also patterns of asthma drug utilization. MATERIALS AND METHODS: Mortality and population data were sourced from the World Health Organization's mortality database. Data on hospitalization were obtained by direct inquiry and from government and scientific publications. Drug use for asthma was expressed as a controller-to-reliever (C:R) ratio (ie, units of inhaled corticosteroids/units of short-acting β-agonists, sold in each country). Time-series regression analyses were used to examine temporal patterns and study association between deaths, hospitalizations, and drug use. RESULTS: Japan showed a decreasing trend in pediatric asthma mortality whereas an increase was observed in Thailand. Hospitalizations decreased in Australia and Singapore but increased in Taiwan, Republic of China. C:R ratios increased significantly across the countries. CONCLUSIONS: Mixed trends in pediatric asthma mortality and hospitalization rates were observed, which coincided with a uniform increase in C:R ratios. This may reflect importance of other aspects of asthma management besides pharmacotherapy.",2009 May 15,"['Chua, Kun Lin', 'Soh, Shu E', 'Ma, Stefan', 'Lee, Bee Wah']",World Allergy Organ J,,,True
8ac43920461faa8a180d94acd6c5a6b35ab8bf7a,PMC,"History of the World Allergy Organization: 1989 to 2006, the XVIII World Allergy Congress, Journal Development, Reorganization, and New Programs",http://dx.doi.org/10.1097/WOX.0b013e31822c9540,PMC3651123,23282542,CC BY,"History of the World Allergy Organization: In 1951, the leaders in allergy from all over the world came together to form the International Association of Allergology and Clinical Immunology (IAACI). For the next 60 years, the allergy world converged at the IAACI triennial meetings, which became biennial in 2003. The international meetings, originally named the International Congress of Allergology and Clinical Immunology (ICACI), are now the World Allergy Congress (WAC) hosted by the World Allergy Organization (WAO). Everyone who has aspired to have worldwide recognition has played a part in IAACI-WAO. The History of the WAO traces the global arc of the allergy field over the past 60 years. The current officers of WAO elected to focus on this rich history, inviting prominent leaders who are interested in being part of this history project to write about their time with IAACI-WAO. This series will be presented in Cancún, México, as part of the XXII World Allergy Congress (December 4-8, 2011). Leading up to the Congress in Cancún, the WAO Journal is presenting segments of the History as part of the ""Notes of Allergy Watchers Series."" Please enjoy. --Michael A. Kaliner, MD Historian, and Past-President (2006-2007), World Allergy Organization",2011 Aug 15,"Kaplan, Allen P",World Allergy Organ J,,,False
52c813a9ed6582f44ae9b23fbb625e0f5a1b7365,PMC,A mobile genetic element with unknown function found in distantly related viruses,http://dx.doi.org/10.1186/1743-422X-10-132,PMC3653767,23618040,CC BY,"BACKGROUND: The genetic element s2m seems to represent one of very few examples of mobile genetic elements in viruses. The function remains obscure and a scattered taxonomical distribution has been reported by numerous groups. METHODS: We have searched GenBank in order to identify all viral accessions that have s2m(−like) sequence motifs. Rigorous phylogenetic analyses and constrained tree topology testing were also performed in order to investigate the apparently mobile nature of s2m. RESULTS: The stem-loop s2m structure can be found in four families of + ssRNA viruses; Astroviridae, Caliciviridae, Picornaviridae and Coronaviridae. In all of these virus families, with the possible exception of Caliciviridae, multiple gains and/or losses of s2m would have to be postulated in order to explain the distribution of this character. CONCLUSIONS: s2m appears to be a mobile genetic element with a unique evolutionary history in all of the four virus families where it can be found. Based on our findings and a review of the current literature on s2m, a hypothesis implying an RNAi-like function for the s2m element is also outlined.",2013 Apr 25,"['Tengs, Torstein', 'Kristoffersen, Anja Bråthen', 'Bachvaroff, Tsvetan R', 'Jonassen, Christine Monceyron']",Virol J,,,True
62a67d1f86138972ae0d79681ddd2a4a75f6dec0,PMC,Carriage of Mycoplasma pneumoniae in the Upper Respiratory Tract of Symptomatic and Asymptomatic Children: An Observational Study,http://dx.doi.org/10.1371/journal.pmed.1001444,PMC3653782,23690754,CC BY,"BACKGROUND: Mycoplasma pneumoniae is thought to be a common cause of respiratory tract infections (RTIs) in children. The diagnosis of M. pneumoniae RTIs currently relies on serological methods and/or the detection of bacterial DNA in the upper respiratory tract (URT). It is conceivable, however, that these diagnostic methods also yield positive results if M. pneumoniae is carried asymptomatically in the URT. Positive results from these tests may therefore not always be indicative of a symptomatic infection. The existence of asymptomatic carriage of M. pneumoniae has not been established. We hypothesized that asymptomatic carriage in children exists and investigated whether colonization and symptomatic infection could be differentiated by current diagnostic methods. METHODS AND FINDINGS: This study was conducted at the Erasmus MC–Sophia Children's Hospital and the after-hours General Practitioners Cooperative in Rotterdam, The Netherlands. Asymptomatic children (n = 405) and children with RTI symptoms (n = 321) aged 3 mo to 16 y were enrolled in a cross-sectional study from July 1, 2008, to November 30, 2011. Clinical data, pharyngeal and nasopharyngeal specimens, and serum samples were collected. The primary objective was to differentiate between colonization and symptomatic infection with M. pneumoniae by current diagnostic methods, especially real-time PCR. M. pneumoniae DNA was detected in 21.2% (95% CI 17.2%–25.2%) of the asymptomatic children and in 16.2% (95% CI 12.2%–20.2%) of the symptomatic children (p = 0.11). Neither serology nor quantitative PCR nor culture differentiated asymptomatic carriage from infection. A total of 202 children were tested for the presence of other bacterial and viral pathogens. Two or more pathogens were found in 56% (63/112) of the asymptomatic children and in 55.5% (50/90) of the symptomatic children. Finally, longitudinal sampling showed persistence of M. pneumoniae in the URT for up to 4 mo. Fifteen of the 21 asymptomatic children with M. pneumoniae and 19 of the 22 symptomatic children with M. pneumoniae in this longitudinal follow-up tested negative after 1 mo. CONCLUSIONS: Although our study has limitations, such as a single study site and limited sample size, our data indicate that the presence of M. pneumoniae in the URT is common in asymptomatic children. The current diagnostic tests for M. pneumoniae are unable to differentiate between asymptomatic carriage and symptomatic infection. Please see later in the article for the Editors' Summary",2013 May 14,"['Spuesens, Emiel B. M.', 'Fraaij, Pieter L. A.', 'Visser, Eline G.', 'Hoogenboezem, Theo', 'Hop, Wim C. J.', 'van Adrichem, Léon N. A.', 'Weber, Frank', 'Moll, Henriette A.', 'Broekman, Berth', 'Berger, Marjolein Y.', 'van Rijsoort-Vos, Tineke', 'van Belkum, Alex', 'Schutten, Martin', 'Pas, Suzan D.', 'Osterhaus, Albert D. M. E.', 'Hartwig, Nico G.', 'Vink, Cornelis', 'van Rossum, Annemarie M. C.']",PLoS Med,,,True
07396bda4a37d13aaf15fdf67d61971549f4162c,PMC,"Viral Etiology of Acute Respiratory Infection in Gansu Province, China, 2011",http://dx.doi.org/10.1371/journal.pone.0064254,PMC3653869,23691184,CC BY,"BACKGROUND: Acute respiratory infections (ARIs) are the leading cause of children and their leading killer. ARIs are responsible for at least six percent of the world's disability and death. Viruses are one of the most common agents causing ARIs. Few studies on the viral etiology and clinical characteristics of ARIs have been performed in the northwest region of China, including Gansu Province. METHODS: Clinical and demographic information and throat swabs were collected from 279 patients from January 1st to December 30st, 2011. Multiplex RT-PCR was performed to detect 16 respiratory viral pathogens. RESULTS: 279 patients were admitted for ARIs. The patients aged from 1 month to 12 years, with the median age of 2 years. Of which, 105 (37.6%) were positive for at least one pathogen. A total of 136 respiratory viral pathogens were identified from the 105 patients. Respiratory syncytial virus (RSV) was the most frequently detected pathogen (26.5%, 36/136), followed by parainfluenza virus (PIV) 1–3 (22.1%, 30/136), human rhinovirus (HRV) (21.3%, 29/136), human coronavirus (CoV) (10.3%, 14/136) and human adenovirus (HAdV) (9.6%, 13/136). Influenza A (Flu A), human metapneumovirus (hMPV) and human bocavirus (BoCA) were found 4.4%, 3.7% and 2.2%, respectively. Influenza B (Flu B) and seasonal influenza A H1N1(sH1N1) were not detected. Single-infections were detected in 30.5% (85/279) of cases. RSV was the most common pathogens in patients under 1 year and showed seasonal variation with peaks during winter and spring. CONCLUSIONS: This paper presents data on the epidemiology of viral pathogens associated with ARIs among children in Gansu Province, China. RSV is most frequently detected in our study. The findings could serve as a reference for local CDC in drawing up further plans to prevent and control ARIs.",2013 May 14,"['Huang, Guohong', 'Yu, Deshan', 'Mao, Naiying', 'Zhu, Zhen', 'Zhang, Hui', 'Jiang, Zhongyi', 'Li, Hongyu', 'Zhang, Yan', 'Shi, Jing', 'Zhang, Shuang', 'Wang, Xinhua', 'Xu, Wenbo']",PLoS One,,,True
6fcc000ecf39dd1da69d94d8cd764790ce96aaba,PMC,Recombinant Vaccines against T. gondii: Comparison between Homologous and Heterologous Vaccination Protocols Using Two Viral Vectors Expressing SAG1,http://dx.doi.org/10.1371/journal.pone.0063201,PMC3654925,23690999,CC BY,"The use of recombinant viral vectors expressing T. gondii antigens is a safe and efficient approach to induce immune response against the parasite and a valuable tool for vaccine development. We have previously protected mice from toxoplasmosis by immunizing the animals with an adenovirus expressing the protein SAG1 (AdSAG1) of T. gondii. We are now looking for ways to improve the vaccination strategy and enhance protection. One limitation of homologous vaccinations (sequential doses of the same vector) is induction of anti-vector immune response that blocks cell transduction, restricts transgene expression and, consequently, compromises the overall outcome of vaccination. One way to avert the effects of anti-vector response is to use different viruses in prime and boost (heterologous vaccination). Bearing this in mind, we generated a modified Vaccinia Virus Ankara encoding SAG1 (MVASAG1), to be tested as boost agent after prime with AdSAG1. Although minor differences were observed in the magnitude of the anti-SAG1 immune response induced by each vaccination protocol, the heterologous immunization with AdSAG1 followed by MVASAG1 resulted in improved capacity to control brain cyst formation in a model of chronic toxoplasmosis in C57BL/6 mice.",2013 May 15,"['Mendes, Érica Araújo', 'Fonseca, Flavio G.', 'Casério, Bárbara M.', 'Colina, Janaína P.', 'Gazzinelli, Ricardo Tostes', 'Caetano, Braulia C.']",PLoS One,,,True
921a97ffd33121fd2623fb899b386adce87a8562,PMC,"Epidemiological analysis of respiratory viral etiology for influenza-like illness during 2010 in Zhuhai, China",http://dx.doi.org/10.1186/1743-422X-10-143,PMC3655035,23651577,CC BY,"BACKGROUND: Influenza-like illnesses (ILI), a subset of acute respiratory infections (ARI), are a significant source of morbidity and mortality worldwide. ILI can be caused by numerous pathogens, however; there is limited information on the etiology and epidemiology of ILI in China. METHODS: We performed a one-year surveillance study (2010) of viral etiology causing ILI and investigated the influence of climate on outbreaks of ILI attributed to viruses at the Outpatient Department of Zhuhai Municipal People’s Hospital in Zhuhai, China. RESULTS: Of the 337,272 outpatients who sought attention in the Outpatient Department of Zhuhai Municipal People’s Hospital in 2010, 3,747 (1.11%) presented with ILI. Of these patients presenting with ILI, 24.66% (924/3,747) had available samples and were enrolled in this study. At least one respiratory virus was identified in 411 patients (44.48%) and 42 (4.55%) were co-infected with two viruses. In patients co-infected with two viruses, respiratory syncytial virus (RSV) was detected in 50% (21/42). Among common viral pathogens detected, significant differences in age distributions were observed in seasonal influenza virus A (sFulA, H3N2) and B (sFluB), pandemic H1N1 2009 influenza viruses (H1N1pdm09), RSV, and adenovirus (ADV). Infections with sFluA (H3N2), sFluB, RSV, and human metapneumovirus (HMPV) had characteristic seasonal patterns. The incidences of sFluA (H3N2), ADV, and RSV correlated with air temperature. Alternatively, the incidence of sFluB correlated with relative air humidity. CONCLUSIONS: These results demonstrate that a wide range of respiratory viral pathogens are circulating in Zhuhai city. This information needs to be considered by clinicians when treating patients presenting with ILI.",2013 May 7,"['Li, Hongxia', 'Wei, Quande', 'Tan, Aijun', 'Wang, Leyi']",Virol J,,,True
43ea5663d460f9bc3ec53ceea11e85b6265a1fef,PMC,New Insights in Recurrent HCV Infection after Liver Transplantation,http://dx.doi.org/10.1155/2013/890517,PMC3655463,23710205,CC BY,"Hepatitis C virus (HCV) is a small-enveloped RNA virus belonging to the Flaviviridae family. Since first identified in 1989, HCV has been estimated to infect 170 million people worldwide. Mostly chronic hepatitis C virus has a uniform natural history, from liver cirrhosis to the development of hepatocellular carcinoma. The current therapy for HCV infection consists of a combination of Pegylated interferon and ribavirin. On the other hand, HCV-related liver disease is also the leading indication for liver transplantation. However, posttransplant HCV re-infection of the graft has been reported to be universal. Furthermore, the graft after HCV re-infection often results in accelerated progression to liver failure. In addition, treatment of recurrent HCV infection after liver transplantation is often compromised by enhanced adverse effects and limited efficacy of interferon-based therapies. Taken together, poor outcome after HCV re-infection, regardless of grafts or recipients, poses a major issue for the hepatologists and transplant surgeons. The aim of this paper is to review several specific aspects regarding HCV re-infection after transplant: risk factors, current therapeutics for HCV in different stages of liver transplantation, cellular function of HCV proteins, and molecular mechanisms of HCV entry. Hopefully, this paper will inspire new strategies and novel inhibitors against recurrent HCV infection after liver transplantation and greatly improve its overall outcome.",2013 Apr 23,"['Hsu, Shih-Hsien', 'Yeh, Ming-Lun', 'Wang, Shen-Nien']",Clin Dev Immunol,,,True
aef63bcba33e2bc1d7a7f1c3e71d7313e2769d98,PMC,Conditional ligands for Asian HLA variants facilitate the definition of CD8(+) T-cell responses in acute and chronic viral diseases,http://dx.doi.org/10.1002/eji.201243088,PMC3655610,23280567,CC BY,"Conditional ligands have enabled the high-throughput production of human leukocyte antigen (HLA) libraries that present defined peptides. Immunomonitoring platforms typically concentrate on restriction elements associated with European ancestry, and such tools are scarce for Asian HLA variants. We report 30 novel irradiation-sensitive ligands, specifically targeting South East Asian populations, which provide 93, 63, and 79% coverage for HLA-A, -B, and -C, respectively. Unique ligands for all 16 HLA types were constructed to provide the desired soluble HLA product in sufficient yield. Peptide exchange was accomplished for all variants as demonstrated by an ELISA-based MHC stability assay. HLA tetramers with redirected specificity could detect antigen-specific CD8(+) T-cell responses against human cytomegalovirus, hepatitis B (HBV), dengue virus (DENV), and Epstein-Barr virus (EBV) infections. The potential of this population-centric HLA library was demonstrated with the characterization of seven novel T-cell epitopes from severe acute respiratory syndrome coronavirus, HBV, and DENV. Posthoc analysis revealed that the majority of responses would be more readily identified by our unbiased discovery approach than through the application of state-of-the-art epitope prediction. This flow cytometry-based technology therefore holds considerable promise for monitoring clinically relevant antigen-specific T-cell responses in populations of distinct ethnicity.",2013 Apr 26,"['Chang, Cynthia X L', 'Tan, Anthony T', 'Or, Ming Yan', 'Toh, Kai Yee', 'Lim, Pei Yiing', 'Chia, Adeline S E', 'Froesig, Thomas M', 'Nadua, Karen D', 'Oh, Hsueh-Ling J', 'Leong, Hoe Nam', 'Hadrup, Sine R', 'Gehring, Adam J', 'Tan, Yee-Joo', 'Bertoletti, Antonio', 'Grotenbreg, Gijsbert M']",Eur J Immunol,,,True
fac9ef6ba1ca4bdb16baad83f0146e6a5c3b906f,PMC,Conditional ligands for Asian HLA variants facilitate the definition of CD8(+) T-cell responses in acute and chronic viral diseases,http://dx.doi.org/10.1002/eji.201243088,PMC3655610,23280567,CC BY,"Conditional ligands have enabled the high-throughput production of human leukocyte antigen (HLA) libraries that present defined peptides. Immunomonitoring platforms typically concentrate on restriction elements associated with European ancestry, and such tools are scarce for Asian HLA variants. We report 30 novel irradiation-sensitive ligands, specifically targeting South East Asian populations, which provide 93, 63, and 79% coverage for HLA-A, -B, and -C, respectively. Unique ligands for all 16 HLA types were constructed to provide the desired soluble HLA product in sufficient yield. Peptide exchange was accomplished for all variants as demonstrated by an ELISA-based MHC stability assay. HLA tetramers with redirected specificity could detect antigen-specific CD8(+) T-cell responses against human cytomegalovirus, hepatitis B (HBV), dengue virus (DENV), and Epstein-Barr virus (EBV) infections. The potential of this population-centric HLA library was demonstrated with the characterization of seven novel T-cell epitopes from severe acute respiratory syndrome coronavirus, HBV, and DENV. Posthoc analysis revealed that the majority of responses would be more readily identified by our unbiased discovery approach than through the application of state-of-the-art epitope prediction. This flow cytometry-based technology therefore holds considerable promise for monitoring clinically relevant antigen-specific T-cell responses in populations of distinct ethnicity.",2013 Apr 26,"['Chang, Cynthia X L', 'Tan, Anthony T', 'Or, Ming Yan', 'Toh, Kai Yee', 'Lim, Pei Yiing', 'Chia, Adeline S E', 'Froesig, Thomas M', 'Nadua, Karen D', 'Oh, Hsueh-Ling J', 'Leong, Hoe Nam', 'Hadrup, Sine R', 'Gehring, Adam J', 'Tan, Yee-Joo', 'Bertoletti, Antonio', 'Grotenbreg, Gijsbert M']",Eur J Immunol,,,True
ee06cad1229867a6389ed8a7aaffb5148dd5f8ed,PMC,Conditional ligands for Asian HLA variants facilitate the definition of CD8(+) T-cell responses in acute and chronic viral diseases,http://dx.doi.org/10.1002/eji.201243088,PMC3655610,23280567,CC BY,"Conditional ligands have enabled the high-throughput production of human leukocyte antigen (HLA) libraries that present defined peptides. Immunomonitoring platforms typically concentrate on restriction elements associated with European ancestry, and such tools are scarce for Asian HLA variants. We report 30 novel irradiation-sensitive ligands, specifically targeting South East Asian populations, which provide 93, 63, and 79% coverage for HLA-A, -B, and -C, respectively. Unique ligands for all 16 HLA types were constructed to provide the desired soluble HLA product in sufficient yield. Peptide exchange was accomplished for all variants as demonstrated by an ELISA-based MHC stability assay. HLA tetramers with redirected specificity could detect antigen-specific CD8(+) T-cell responses against human cytomegalovirus, hepatitis B (HBV), dengue virus (DENV), and Epstein-Barr virus (EBV) infections. The potential of this population-centric HLA library was demonstrated with the characterization of seven novel T-cell epitopes from severe acute respiratory syndrome coronavirus, HBV, and DENV. Posthoc analysis revealed that the majority of responses would be more readily identified by our unbiased discovery approach than through the application of state-of-the-art epitope prediction. This flow cytometry-based technology therefore holds considerable promise for monitoring clinically relevant antigen-specific T-cell responses in populations of distinct ethnicity.",2013 Apr 26,"['Chang, Cynthia X L', 'Tan, Anthony T', 'Or, Ming Yan', 'Toh, Kai Yee', 'Lim, Pei Yiing', 'Chia, Adeline S E', 'Froesig, Thomas M', 'Nadua, Karen D', 'Oh, Hsueh-Ling J', 'Leong, Hoe Nam', 'Hadrup, Sine R', 'Gehring, Adam J', 'Tan, Yee-Joo', 'Bertoletti, Antonio', 'Grotenbreg, Gijsbert M']",Eur J Immunol,,,True
b3e7a3736c037ca082235e695e686cce2a4790a1,PMC,The Secret Life of Viral Entry Glycoproteins: Moonlighting in Immune Evasion,http://dx.doi.org/10.1371/journal.ppat.1003258,PMC3656028,23696729,CC BY,,2013 May 16,"['Cook, Jonathan D.', 'Lee, Jeffrey E.']",PLoS Pathog,,,True
74f36e3fdaac0583dace5a4a9031bc79d154c798,PMC,Abortive Lytic Reactivation of KSHV in CBF1/CSL Deficient Human B Cell Lines,http://dx.doi.org/10.1371/journal.ppat.1003336,PMC3656114,23696732,CC BY,"Since Kaposi's sarcoma associated herpesvirus (KSHV) establishes a persistent infection in human B cells, B cells are a critical compartment for viral pathogenesis. RTA, the replication and transcription activator of KSHV, can either directly bind to DNA or use cellular DNA binding factors including CBF1/CSL as DNA adaptors. In addition, the viral factors LANA1 and vIRF4 are known to bind to CBF1/CSL and modulate RTA activity. To analyze the contribution of CBF1/CSL to reactivation in human B cells, we have successfully infected DG75 and DG75 CBF1/CSL knock-out cell lines with recombinant KSHV.219 and selected for viral maintenance by selective medium. Both lines maintained the virus irrespective of their CBF1/CSL status. Viral reactivation could be initiated in both B cell lines but viral genome replication was attenuated in CBF1/CSL deficient lines, which also failed to produce detectable levels of infectious virus. Induction of immediate early, early and late viral genes was impaired in CBF1/CSL deficient cells at multiple stages of the reactivation process but could be restored to wild-type levels by reintroduction of CBF1/CSL. To identify additional viral RTA target genes, which are directly controlled by CBF1/CSL, we analyzed promoters of a selected subset of viral genes. We show that the induction of the late viral genes ORF29a and ORF65 by RTA is strongly enhanced by CBF1/CSL. Orthologs of ORF29a in other herpesviruses are part of the terminase complex required for viral packaging. ORF65 encodes the small capsid protein essential for capsid shell assembly. Our study demonstrates for the first time that in human B cells viral replication can be initiated in the absence of CBF1/CSL but the reactivation process is severely attenuated at all stages and does not lead to virion production. Thus, CBF1/CSL acts as a global hub which is used by the virus to coordinate the lytic cascade.",2013 May 16,"['Scholz, Barbara A.', 'Harth-Hertle, Marie L.', 'Malterer, Georg', 'Haas, Juergen', 'Ellwart, Joachim', 'Schulz, Thomas F.', 'Kempkes, Bettina']",PLoS Pathog,,,True
a13c79aab29bf6afdf2fe0cbd6269b1941e77ee0,PMC,"Risk Perception, Preventive Behaviors, and Vaccination Coverage in the Korean Population during the 2009–2010 Pandemic Influenza A (H1N1): Comparison between High-Risk Group and Non–High-Risk Group",http://dx.doi.org/10.1371/journal.pone.0064230,PMC3656839,23691175,CC BY,"BACKGROUND: This study was carried out to estimate the vaccination coverage, public perception, and preventive behaviors against pandemic influenza A (H1N1) and to understand the motivation and barriers to vaccination between high-risk and non–high-risk groups during the outbreak of pandemic influenza A (H1N1). METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional nationwide telephone survey of 1,650 community-dwelling Korean adults aged 19 years and older was conducted in the later stage of the 2009–2010 pandemic influenza A (H1N1) outbreak. The questionnaire identified the demographics, vaccination status of participants and all household members, barriers to non-vaccination, perceived threat, and preventive behaviors. In Korea, the overall rate of pandemic influenza vaccination coverage in the surveyed population was 15.5%; vaccination coverage in the high-risk group and non–high-risk group was 47.3% and 8.0%, respectively. In the high-risk group, the most important triggering event for vaccination was receiving a notice from a public health organization. In the non–high-risk group, vaccination was more strongly influenced by previous experience with influenza or mass media campaigns. In both groups, the most common reasons for not receiving vaccination was that their health was sufficient to forgo the vaccination, and lack of time. There was no significant difference in how either group perceived the threat or adopted preventive behavior. The predictive factors for pandemic influenza vaccination were being elderly (age ≥65 years), prior seasonal influenza vaccination, and chronic medical disease. CONCLUSIONS/SIGNIFICANCE: With the exception of vaccination coverage, the preventive behaviors of the high-risk group were not different from those of the non–high-risk group during the 2009–2010 pandemic. For future pandemic preparedness planning, it is crucial to reinforce preventive behaviors to avoid illness before vaccination and to increase vaccination coverage in the high-risk group.",2013 May 17,"['Heo, Jung Yeon', 'Chang, Soung Hoon', 'Go, Min Jung', 'Kim, Young Mee', 'Gu, Sun Hye', 'Chun, Byung Chul']",PLoS One,,,True
2fc84e709c4978a92c3f4168a6c145080d1b046b,PMC,Presence of Infectious Bronchitis Virus Strain CK/CH/LDL/97I in the Middle East,http://dx.doi.org/10.5402/2012/201721,PMC3658599,23738118,CC BY,"Infectious bronchitis virus (IBV) is a very dynamic and evolving virus, causing major economic losses to the global poultry industry. In early 2011, respiratory disease outbreaks were investigated in Iraq, Jordan, and Saudi Arabia. Five IBV isolates (JOA2, JOA4, Saudi-1, Saudi-2, and Iraqi IBV) were detected by diagnostic-nested nucleocapsid RT-PCR. Strain identification was characterised by sequencing and phylogenetic analysis of the amplified hypervariable region of the spike 1 (S1) gene. These five IBV isolates were found to be of the IBV strain CK/CH/LDL/97I. Nucleotide identity between these five IBV isolates ranged from 96.9% to 99.7%, and between these isolates and the CK/CH/LDL/97I strain in the range of 96.6–99.1%. The sequenced fragment of the S1 gene of the CK/CH/LDL/97I strain had less than 80% nucleotide identity to the IBV vaccine strains commonly used in the Middle East (M41 and H120). The presence of these CK/CH/LDL/97I-like strains may account for vaccination failure against IBV, since all IBV isolates were from vaccinated chickens. In this paper, we documented for the first time the presence of IBV strain CK/CH/LDL/97I in the Middle East. This strain is known to have originated in China and Taiwan.",2012 Apr 11,"['Ababneh, Mustafa', 'Dalab, Abd Elhafeed', 'Alsaad, Saad', 'Al-Zghoul, Mohammad']",ISRN Vet Sci,,,True
7f302add8b117514b8393d55f49c3ded276faf94,PMC,"Rapid, responsive, relevant (R3) research: a call for a rapid learning health research enterprise",http://dx.doi.org/10.1186/2001-1326-2-10,PMC3658895,23663660,CC BY,"Our current health research enterprise is painstakingly slow and cumbersome, and its results seldom translate into practice. The slow pace of health research contributes to findings that are less relevant and potentially even obsolete. To produce more rapid, responsive, and relevant research, we propose approaches that increase relevance via greater stakeholder involvement, speed research via innovative designs, streamline review processes, and create and/or better leverage research infrastructure. Broad stakeholder input integrated throughout the research process can both increase relevance and facilitate study procedures. More flexible and rapid research designs should be considered before defaulting to the traditional two-arm randomized controlled trial (RCT), but even traditional RCTs can be designed for more rapid findings. Review processes for grant applications, IRB protocols, and manuscript submissions can be better streamlined to minimize delays. Research infrastructures such as rapid learning systems and other health information technologies can be leveraged to rapidly evaluate new and existing treatments, and alleviate the extensive recruitment delays common in traditional research. These and other approaches are feasible but require a culture shift among the research community to value not only methodological rigor, but also the pace and relevance of research.",2013 May 10,"['Riley, William T', 'Glasgow, Russell E', 'Etheredge, Lynn', 'Abernethy, Amy P']",Clin Transl Med,,,True
04799a6c57e1d3f9488b24a4fc2580bbb3818665,PMC,Development of porcine rotavirus vp6 protein based ELISA for differentiation of this virus and other viruses,http://dx.doi.org/10.1186/1743-422X-10-91,PMC3658953,23517810,CC BY,"BACKGROUND: The context and purpose of the study included 1) bacterial expression of viral protein 6 (VP6) of porcine rotavirus (PRV) and generation of rabbit polyclonal antiserum to the VP6 protein; 3) establishment of a discrimination ELISA to distinguish PRV from a panel of other porcine viruses. RESULTS: The VP6 gene of PRV isolate DN30209 amplified by reverse transcription-PCR was 1356 bp containing a complete open reading frame (ORF) encoding 397 amino acids. Sequence comparison and phylogenetic analysis indicated that PRV DN30209 may belong to group A of rotavirus. Bacterially expressed VP6 was expressed in E.coli and anti-VP6 antibody was capable of distinguishing PRV from Porcine transmissible gastroenteritis virus, Porcine epidemic diarrhea virus, Porcine circovirus type II, Porcine reproductive and respiratory syndrome virus, Porcine pseudorabies virus and Porcine parvovirus. CONCLUSIONS: PRV VP6 expressed in E. coli can be used to generate antibodies in rabbit; anti-VP6 serum antibody can be used as good diagnostic reagents for detection of PRV.",2013 Mar 22,"['Zhu, Jiayi', 'Yang, Qing', 'Cao, Liyan', 'Dou, Xiujing', 'Zhao, Jianguo', 'Zhu, Weijuan', 'Ding, Fan', 'Bu, Ri-e', 'Suo, Siqingaowa', 'Ren, Yudong', 'Li, Guangxing', 'Ren, Xiaofeng']",Virol J,,,True
b58b4809e706401c8f5851d5b0d2be93b8f431cf,PMC,Ecological Factors Associated with European Bat Lyssavirus Seroprevalence in Spanish Bats,http://dx.doi.org/10.1371/journal.pone.0064467,PMC3659107,23700480,CC0,"Bats have been proposed as major reservoirs for diverse emerging infectious viral diseases, with rabies being the best known in Europe. However, studies exploring the ecological interaction between lyssaviruses and their natural hosts are scarce. This study completes our active surveillance work on Spanish bat colonies that began in 1992. Herein, we analyzed ecological factors that might affect the infection dynamics observed in those colonies. Between 2001 and 2011, we collected and tested 2,393 blood samples and 45 dead bats from 25 localities and 20 bat species. The results for dead confirmed the presence of EBLV-1 RNA in six species analyzed (for the first time in Myotis capaccinii). Samples positive for European bat lyssavirus-1 (EBLV-1)–neutralizing antibodies were detected in 68% of the localities sampled and in 13 bat species, seven of which were found for the first time (even in Myotis daubentonii, a species to date always linked to EBLV-2). EBLV-1 seroprevalence (20.7%) ranged between 11.1 and 40.2% among bat species and seasonal variation was observed, with significantly higher antibody prevalence in summer (July). EBLV-1 seroprevalence was significantly associated with colony size and species richness. Higher seroprevalence percentages were found in large multispecific colonies, suggesting that intra- and interspecific contacts are major risk factors for EBLV-1 transmission in bat colonies. Although bat-roosting behavior strongly determines EBLV-1 variability, we also found some evidence that bat phylogeny might be involved in bat-species seroprevalence. The results of this study highlight the importance of life history and roost ecology in understanding EBLV-1–prevalence patterns in bat colonies and also provide useful information for public health officials.",2013 May 20,"['Serra-Cobo, Jordi', 'López-Roig, Marc', 'Seguí, Magdalena', 'Sánchez, Luisa Pilar', 'Nadal, Jacint', 'Borrás, Miquel', 'Lavenir, Rachel', 'Bourhy, Hervé']",PLoS One,,,True
0ba1801a150e25b029cf3c2a38573435b21dea80,PMC,Identifying SARS-CoV Membrane Protein Amino Acid Residues Linked to Virus-Like Particle Assembly,http://dx.doi.org/10.1371/journal.pone.0064013,PMC3659117,23700447,CC BY,"Severe acute respiratory syndrome coronavirus (SARS-CoV) membrane (M) proteins are capable of self-assembly and release in the form of membrane-enveloped vesicles, and of forming virus-like particles (VLPs) when coexpressed with SARS-CoV nucleocapsid (N) protein. According to previous deletion analyses, M self-assembly involves multiple M sequence regions. To identify important M amino acid residues for VLP assembly, we coexpressed N with multiple M mutants containing substitution mutations at the amino-terminal ectodomain, carboxyl-terminal endodomain, or transmembrane segments. Our results indicate that a dileucine motif in the endodomain tail (218LL219) is required for efficient N packaging into VLPs. Results from cross-linking VLP analyses suggest that the cysteine residues 63, 85 and 158 are not in close proximity to the M dimer interface. We noted a significant reduction in M secretion due to serine replacement for C158, but not for C63 or C85. Further analysis suggests that C158 is involved in M-N interaction. In addition to mutations of the highly conserved 107-SWWSFNPE-114 motif, substitutions at codons W19, W57, P58, W91, Y94 or F95 all resulted in significantly reduced VLP yields, largely due to defective M secretion. VLP production was not significantly affected by a tryptophan replacement of Y94 or F95 or a phenylalanine replacement of W19, W57 or W91. Combined, these results indicate the involvement of specific M amino acids during SARS-CoV virus assembly, and suggest that aromatic residue retention at specific positions is critical for M function in terms of directing virus assembly.",2013 May 20,"['Tseng, Ying-Tzu', 'Chang, Chia-Hui', 'Wang, Shiu-Mei', 'Huang, Kuo-Jung', 'Wang, Chin-Tien']",PLoS One,,,True
e64c852725ef6bf2abf9071b522c10917b50ac6e,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,True
94becb8706cfe183f2debc7f9067513974a1a552,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,False
419a452d263cb907fb5c6b3e47c96aebabb78d64,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,False
145a6aff8c6d58f46bb0eb5671a9cabae0d939fc,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,False
14f9f4f16ad081a427b8f39d7fabe109c85acb9b,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,False
d6225b3ffed6a2077e3334b06526faa8b977182a,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,False
a96ad20c7fe3d4b57fc694c5957fa0404091f3de,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,False
d6a600b3dbaf7490b4b1fd35165333b03f7f2151,PMC,Platelet activation suppresses HIV-1 infection of T cells,http://dx.doi.org/10.1186/1742-4690-10-48,PMC3660175,23634812,CC BY,"BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.",2013 May 1,"['Solomon Tsegaye, Theodros', 'Gnirß, Kerstin', 'Rahe-Meyer, Niels', 'Kiene, Miriam', 'Krämer-Kühl, Annika', 'Behrens, Georg', 'Münch, Jan', 'Pöhlmann, Stefan']",Retrovirology,,,False
0cd911d564b693ebedf57fa37c28b8ea5705c174,PMC,"Laboratory Surveillance of Influenza-Like Illness in Seven Teaching Hospitals, South Korea: 2011–2012 Season",http://dx.doi.org/10.1371/journal.pone.0064295,PMC3661466,23717587,CC BY,"BACKGROUND: A well-constructed and properly operating influenza surveillance scheme is essential for public health. This study was conducted to evaluate the distribution of respiratory viruses in patients with influenza-like illness (ILI) through the first teaching hospital-based surveillance scheme for ILI in South Korea. METHODS: Respiratory specimens were obtained from adult patients (≥18 years) who visited the emergency department (ED) with ILI from week 40, 2011 to week 22, 2012. Multiplex PCR was performed to detect respiratory viruses: influenza virus, adenovirus, coronavirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, parainfluenza virus, bocavirus, and enterovirus. RESULTS: Among 1,983 patients who visited the ED with ILI, 811 (40.9%) were male. The median age of patients was 43 years. Influenza vaccination rate was 21.7% (430/1,983) during the 2011–2012 season. At least one comorbidity was found in 18% of patients. The positive rate of respiratory viruses was 52.1% (1,033/1,983) and the total number of detected viruses was 1,100. Influenza A virus was the dominant agent (677, 61.5%) in all age groups. The prevalence of human metapneumovirus was higher in patients more than 50 years old, while adenovirus was detected only in younger adults. In 58 (5.6%) cases, two or more respiratory viruses were detected. The co-incidence case was identified more frequently in patients with hematologic malignancy or organ transplantation recipients, however it was not related to clinical outcomes. CONCLUSION: This study is valuable as the first extensive laboratory surveillance of the epidemiology of respiratory viruses in ILI patients through a teaching hospital-based influenza surveillance system in South Korea.",2013 May 22,"['Noh, Ji Yun', 'Song, Joon Young', 'Cheong, Hee Jin', 'Choi, Won Suk', 'Lee, Jacob', 'Lee, Jin-Soo', 'Wie, Seong-Heon', 'Jeong, Hye Won', 'Kim, Young Keun', 'Choi, Sung Hyuk', 'Han, Seung Baik', 'So, Byung-Hak', 'Kim, Hyun', 'Kim, Woo Joo']",PLoS One,,,True
71b9d32718c8ba343468da22dc28314f84b852ec,PMC,A Lattice Model for Influenza Spreading,http://dx.doi.org/10.1371/journal.pone.0063935,PMC3661600,23717512,CC BY,"We construct a stochastic SIR model for influenza spreading on a D-dimensional lattice, which represents the dynamic contact network of individuals. An age distributed population is placed on the lattice and moves on it. The displacement from a site to a nearest neighbor empty site, allows individuals to change the number and identities of their contacts. The dynamics on the lattice is governed by an attractive interaction between individuals belonging to the same age-class. The parameters, which regulate the pattern dynamics, are fixed fitting the data on the age-dependent daily contact numbers, furnished by the Polymod survey. A simple SIR transmission model with a nearest neighbors interaction and some very basic adaptive mobility restrictions complete the model. The model is validated against the age-distributed Italian epidemiological data for the influenza A(H1N1) during the [Image: see text] season, with sensible predictions for the epidemiological parameters. For an appropriate topology of the lattice, we find that, whenever the accordance between the contact patterns of the model and the Polymod data is satisfactory, there is a good agreement between the numerical and the experimental epidemiological data. This result shows how rich is the information encoded in the average contact patterns of individuals, with respect to the analysis of the epidemic spreading of an infectious disease.",2013 May 22,"['Liccardo, Antonella', 'Fierro, Annalisa']",PLoS One,,,True
c82205e91bbd1135020b4fdf0d9df2654c66650a,PMC,Global Organization of a Positive-strand RNA Virus Genome,http://dx.doi.org/10.1371/journal.ppat.1003363,PMC3662671,23717202,CC BY,"The genomes of plus-strand RNA viruses contain many regulatory sequences and structures that direct different viral processes. The traditional view of these RNA elements are as local structures present in non-coding regions. However, this view is changing due to the discovery of regulatory elements in coding regions and functional long-range intra-genomic base pairing interactions. The ∼4.8 kb long RNA genome of the tombusvirus tomato bushy stunt virus (TBSV) contains these types of structural features, including six different functional long-distance interactions. We hypothesized that to achieve these multiple interactions this viral genome must utilize a large-scale organizational strategy and, accordingly, we sought to assess the global conformation of the entire TBSV genome. Atomic force micrographs of the genome indicated a mostly condensed structure composed of interconnected protrusions extending from a central hub. This configuration was consistent with the genomic secondary structure model generated using high-throughput selective 2′-hydroxyl acylation analysed by primer extension (i.e. SHAPE), which predicted different sized RNA domains originating from a central region. Known RNA elements were identified in both domain and inter-domain regions, and novel structural features were predicted and functionally confirmed. Interestingly, only two of the six long-range interactions known to form were present in the structural model. However, for those interactions that did not form, complementary partner sequences were positioned relatively close to each other in the structure, suggesting that the secondary structure level of viral genome structure could provide a basic scaffold for the formation of different long-range interactions. The higher-order structural model for the TBSV RNA genome provides a snapshot of the complex framework that allows multiple functional components to operate in concert within a confined context.",2013 May 23,"['Wu, Baodong', 'Grigull, Jörg', 'Ore, Moriam O.', 'Morin, Sylvie', 'White, K. Andrew']",PLoS Pathog,,,True
054e3e247ad11de2be71be7215e30a44222271ab,PMC,Transient Oligomerization of the SARS-CoV N Protein – Implication for Virus Ribonucleoprotein Packaging,http://dx.doi.org/10.1371/journal.pone.0065045,PMC3662775,23717688,CC BY,"The nucleocapsid (N) phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV) packages the viral genome into a helical ribonucleocapsid and plays a fundamental role during viral self-assembly. The N protein consists of two structural domains interspersed between intrinsically disordered regions and dimerizes through the C-terminal structural domain (CTD). A key activity of the protein is the ability to oligomerize during capsid formation by utilizing the dimer as a building block, but the structural and mechanistic bases of this activity are not well understood. By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that CTD acts as a primary transient oligomerization domain in solution. The data is consistent with the helical oligomer packing model of N protein observed in crystal. A systematic study of the oligomerization behavior revealed that altering the intermolecular electrostatic repulsion through changes in solution salt concentration or phosphorylation-mimicking mutations affects oligomerization propensity. We propose a biophysical mechanism where electrostatic repulsion acts as a switch to regulate N protein oligomerization.",2013 May 23,"['Chang, Chung-ke', 'Chen, Chia-Min Michael', 'Chiang, Ming-hui', 'Hsu, Yen-lan', 'Huang, Tai-huang']",PLoS One,,,True
4ab3c0ea7ec522f4fd4e3a2d92a975d3a054ca88,PMC,Transient Oligomerization of the SARS-CoV N Protein – Implication for Virus Ribonucleoprotein Packaging,http://dx.doi.org/10.1371/journal.pone.0065045,PMC3662775,23717688,CC BY,"The nucleocapsid (N) phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV) packages the viral genome into a helical ribonucleocapsid and plays a fundamental role during viral self-assembly. The N protein consists of two structural domains interspersed between intrinsically disordered regions and dimerizes through the C-terminal structural domain (CTD). A key activity of the protein is the ability to oligomerize during capsid formation by utilizing the dimer as a building block, but the structural and mechanistic bases of this activity are not well understood. By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that CTD acts as a primary transient oligomerization domain in solution. The data is consistent with the helical oligomer packing model of N protein observed in crystal. A systematic study of the oligomerization behavior revealed that altering the intermolecular electrostatic repulsion through changes in solution salt concentration or phosphorylation-mimicking mutations affects oligomerization propensity. We propose a biophysical mechanism where electrostatic repulsion acts as a switch to regulate N protein oligomerization.",2013 May 23,"['Chang, Chung-ke', 'Chen, Chia-Min Michael', 'Chiang, Ming-hui', 'Hsu, Yen-lan', 'Huang, Tai-huang']",PLoS One,,,False
0d5be5a4268da7c08b478ca36721d46bd67bbe69,PMC,Effect of avian influenza A H5N1 infection on the expression of microRNA-141 in human respiratory epithelial cells,http://dx.doi.org/10.1186/1471-2180-13-104,PMC3663648,23663545,CC BY,"BACKGROUND: Avian influenza remains a serious threat to human health. The consequence of human infection varies markedly among different subtypes of avian influenza viruses. In addition to viral factors, the difference in host cellular response is likely to play a critical role. This study aims at elucidating how avian influenza infection perturbs the host’s miRNA regulatory pathways that may lead to adverse pathological events, such as cytokine storm, using the miRNA microarray approach. RESULTS: The results showed that dysregulation of miRNA expression was mainly observed in highly pathogenic avian influenza A H5N1 infection. We found that miR-21*, miR-100*, miR-141, miR-574-3p, miR-1274a and miR1274b were differentially expressed in response to influenza A virus infection. Interestingly, we demonstrated that miR-141, which was more highly induced by H5N1 than by H1N1 (p < 0.05), had an ability to suppress the expression of a cytokine - transforming growth factor (TGF)-β2. This was supported by the observation that the inhibitory effect could be reversed by antagomiR-141. CONCLUSIONS: Since TGF-β2 is an important cytokine that can act as both an immunosuppressive agent and a potent proinflammatory molecule through its ability to attract and regulate inflammatory molecules, and previous report showed that only seasonal influenza H1N1 (but not the other avian influenza subtypes) could induce a persistent expression of TGF-β2, we speculate that the modulation of TGF-β2 expression by different influenza subtypes via miR-141 might be a critical step for determining the outcome of either normal or excessive inflammation progression.",2013 May 10,"['Lam, Wai-Yip', 'Yeung, Apple Chung-Man', 'Ngai, Karry Lei-Ka', 'Li, Man-Shan', 'To, Ka-Fai', 'Tsui, Stephen Kwok-Wing', 'Chan, Paul Kay-Sheung']",BMC Microbiol,,,True
5e0504a1c581c36bbf2c2c97439b87b9834b108b,PMC,Induction of Interferon-Stimulated Genes on the IL-4 Response Axis by Epstein-Barr Virus Infected Human B Cells; Relevance to Cellular Transformation,http://dx.doi.org/10.1371/journal.pone.0064868,PMC3664578,23724103,CC BY,"Epstein-Barr virus (EBV) is an oncogenic virus that is associated with the pathogenesis of several human lymphoid malignancies, including Hodgkin's lymphoma. Infection of normal resting B cells with EBV results in activation to lymphoblasts that are phenotypically similar to those generated by physiological stimulation with CD40L plus IL-4. One important difference is that infection leads to the establishment of permanently growing lymphoblastoid cell lines, whereas CD40L/IL-4 blasts have finite proliferation lifespans. To identify early events which might later determine why EBV infected blasts go on to establish transformed cell lines, we performed global transcriptome analyses on resting B cells and on EBV and CD40L/IL-4 blasts after 7 days culture. As anticipated there was considerable overlap in the transcriptomes of the two types of lymphoblasts when compared to the original resting B cells, reflecting common changes associated with lymphocyte activation and proliferation. Of interest to us was a subset of 255 genes that were differentially expressed between EBV and CD40L/IL-4 blasts. Genes which were more highly expressed in EBV blasts were substantially and significantly enriched for a set of interferon-stimulated genes which on further in silico analyses were found to be repressed by IL-4 in other cell contexts and to be up-regulated in micro-dissected malignant cells from Hodgkin's lymphoma biopsies when compared to their normal germinal center cell counterparts. We hypothesized that EBV and IL-4 were targeting and discordantly regulating a common set of genes. This was supported experimentally in our B cell model where IL-4 stimulation partially reversed transcriptional changes which follow EBV infection and it impaired the efficiency of EBV-induced B cell transformation. Taken together, these data suggest that the discordant regulation of interferon and IL-4 pathway genes by EBV that occurs early following infection of B cells has relevance to the development or maintenance of an EBV-associated malignancy.",2013 May 27,"['Smith, Nikki', 'Tierney, Rosemary', 'Wei, Wenbin', 'Vockerodt, Martina', 'Murray, Paul G.', 'Woodman, Ciaran B.', 'Rowe, Martin']",PLoS One,,,True
dca48fcd1b8a28f470494d64ea3811707e28766b,PMC,Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein,http://dx.doi.org/10.1371/journal.pbio.1001571,PMC3665890,23723737,CC BY,"Transferrin Receptor (TfR1) is the cell-surface receptor that regulates iron uptake into cells, a process that is fundamental to life. However, TfR1 also facilitates the cellular entry of multiple mammalian viruses. We use evolutionary and functional analyses of TfR1 in the rodent clade, where two families of viruses bind this receptor, to mechanistically dissect how essential housekeeping genes like TFR1 successfully balance the opposing selective pressures exerted by host and virus. We find that while the sequence of rodent TfR1 is generally conserved, a small set of TfR1 residue positions has evolved rapidly over the speciation of rodents. Remarkably, all of these residues correspond to the two virus binding surfaces of TfR1. We show that naturally occurring mutations at these positions block virus entry while simultaneously preserving iron-uptake functionalities, both in rodent and human TfR1. Thus, by constantly replacing the amino acids encoded at just a few residue positions, TFR1 divorces adaptation to ever-changing viruses from preservation of key cellular functions. These dynamics have driven genetic divergence at the TFR1 locus that now enforces species-specific barriers to virus transmission, limiting both the cross-species and zoonotic transmission of these viruses.",2013 May 28,"['Demogines, Ann', 'Abraham, Jonathan', 'Choe, Hyeryun', 'Farzan, Michael', 'Sawyer, Sara L.']",PLoS Biol,,,True
1919d046fbf9c2b918e861d3c456876d110d5efb,PMC,Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein,http://dx.doi.org/10.1371/journal.pbio.1001571,PMC3665890,23723737,CC BY,"Transferrin Receptor (TfR1) is the cell-surface receptor that regulates iron uptake into cells, a process that is fundamental to life. However, TfR1 also facilitates the cellular entry of multiple mammalian viruses. We use evolutionary and functional analyses of TfR1 in the rodent clade, where two families of viruses bind this receptor, to mechanistically dissect how essential housekeeping genes like TFR1 successfully balance the opposing selective pressures exerted by host and virus. We find that while the sequence of rodent TfR1 is generally conserved, a small set of TfR1 residue positions has evolved rapidly over the speciation of rodents. Remarkably, all of these residues correspond to the two virus binding surfaces of TfR1. We show that naturally occurring mutations at these positions block virus entry while simultaneously preserving iron-uptake functionalities, both in rodent and human TfR1. Thus, by constantly replacing the amino acids encoded at just a few residue positions, TFR1 divorces adaptation to ever-changing viruses from preservation of key cellular functions. These dynamics have driven genetic divergence at the TFR1 locus that now enforces species-specific barriers to virus transmission, limiting both the cross-species and zoonotic transmission of these viruses.",2013 May 28,"['Demogines, Ann', 'Abraham, Jonathan', 'Choe, Hyeryun', 'Farzan, Michael', 'Sawyer, Sara L.']",PLoS Biol,,,False
4c0660d807475373cd5e4bf4ba268a1005b87712,PMC,Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein,http://dx.doi.org/10.1371/journal.pbio.1001571,PMC3665890,23723737,CC BY,"Transferrin Receptor (TfR1) is the cell-surface receptor that regulates iron uptake into cells, a process that is fundamental to life. However, TfR1 also facilitates the cellular entry of multiple mammalian viruses. We use evolutionary and functional analyses of TfR1 in the rodent clade, where two families of viruses bind this receptor, to mechanistically dissect how essential housekeeping genes like TFR1 successfully balance the opposing selective pressures exerted by host and virus. We find that while the sequence of rodent TfR1 is generally conserved, a small set of TfR1 residue positions has evolved rapidly over the speciation of rodents. Remarkably, all of these residues correspond to the two virus binding surfaces of TfR1. We show that naturally occurring mutations at these positions block virus entry while simultaneously preserving iron-uptake functionalities, both in rodent and human TfR1. Thus, by constantly replacing the amino acids encoded at just a few residue positions, TFR1 divorces adaptation to ever-changing viruses from preservation of key cellular functions. These dynamics have driven genetic divergence at the TFR1 locus that now enforces species-specific barriers to virus transmission, limiting both the cross-species and zoonotic transmission of these viruses.",2013 May 28,"['Demogines, Ann', 'Abraham, Jonathan', 'Choe, Hyeryun', 'Farzan, Michael', 'Sawyer, Sara L.']",PLoS Biol,,,False
5bfb1815d1873f05bde8557c59d26b840c7de981,PMC,Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein,http://dx.doi.org/10.1371/journal.pbio.1001571,PMC3665890,23723737,CC BY,"Transferrin Receptor (TfR1) is the cell-surface receptor that regulates iron uptake into cells, a process that is fundamental to life. However, TfR1 also facilitates the cellular entry of multiple mammalian viruses. We use evolutionary and functional analyses of TfR1 in the rodent clade, where two families of viruses bind this receptor, to mechanistically dissect how essential housekeeping genes like TFR1 successfully balance the opposing selective pressures exerted by host and virus. We find that while the sequence of rodent TfR1 is generally conserved, a small set of TfR1 residue positions has evolved rapidly over the speciation of rodents. Remarkably, all of these residues correspond to the two virus binding surfaces of TfR1. We show that naturally occurring mutations at these positions block virus entry while simultaneously preserving iron-uptake functionalities, both in rodent and human TfR1. Thus, by constantly replacing the amino acids encoded at just a few residue positions, TFR1 divorces adaptation to ever-changing viruses from preservation of key cellular functions. These dynamics have driven genetic divergence at the TFR1 locus that now enforces species-specific barriers to virus transmission, limiting both the cross-species and zoonotic transmission of these viruses.",2013 May 28,"['Demogines, Ann', 'Abraham, Jonathan', 'Choe, Hyeryun', 'Farzan, Michael', 'Sawyer, Sara L.']",PLoS Biol,,,False
08ee65d70ad0dae18dd402eb531103c2dfbbeffb,PMC,Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein,http://dx.doi.org/10.1371/journal.pbio.1001571,PMC3665890,23723737,CC BY,"Transferrin Receptor (TfR1) is the cell-surface receptor that regulates iron uptake into cells, a process that is fundamental to life. However, TfR1 also facilitates the cellular entry of multiple mammalian viruses. We use evolutionary and functional analyses of TfR1 in the rodent clade, where two families of viruses bind this receptor, to mechanistically dissect how essential housekeeping genes like TFR1 successfully balance the opposing selective pressures exerted by host and virus. We find that while the sequence of rodent TfR1 is generally conserved, a small set of TfR1 residue positions has evolved rapidly over the speciation of rodents. Remarkably, all of these residues correspond to the two virus binding surfaces of TfR1. We show that naturally occurring mutations at these positions block virus entry while simultaneously preserving iron-uptake functionalities, both in rodent and human TfR1. Thus, by constantly replacing the amino acids encoded at just a few residue positions, TFR1 divorces adaptation to ever-changing viruses from preservation of key cellular functions. These dynamics have driven genetic divergence at the TFR1 locus that now enforces species-specific barriers to virus transmission, limiting both the cross-species and zoonotic transmission of these viruses.",2013 May 28,"['Demogines, Ann', 'Abraham, Jonathan', 'Choe, Hyeryun', 'Farzan, Michael', 'Sawyer, Sara L.']",PLoS Biol,,,True
3b124808cb49c3530b23b6fda834fcbbc8af1988,PMC,"Trends in parameterization, economics and host behaviour in influenza pandemic modelling: a review and reporting protocol",http://dx.doi.org/10.1186/1742-7622-10-3,PMC3666982,23651557,CC BY,"BACKGROUND: The volume of influenza pandemic modelling studies has increased dramatically in the last decade. Many models incorporate now sophisticated parameterization and validation techniques, economic analyses and the behaviour of individuals. METHODS: We reviewed trends in these aspects in models for influenza pandemic preparedness that aimed to generate policy insights for epidemic management and were published from 2000 to September 2011, i.e. before and after the 2009 pandemic. RESULTS: We find that many influenza pandemics models rely on parameters from previous modelling studies, models are rarely validated using observed data and are seldom applied to low-income countries. Mechanisms for international data sharing would be necessary to facilitate a wider adoption of model validation. The variety of modelling decisions makes it difficult to compare and evaluate models systematically. CONCLUSIONS: We propose a model Characteristics, Construction, Parameterization and Validation aspects protocol (CCPV protocol) to contribute to the systematisation of the reporting of models with an emphasis on the incorporation of economic aspects and host behaviour. Model reporting, as already exists in many other fields of modelling, would increase confidence in model results, and transparency in their assessment and comparison.",2013 May 7,"['Carrasco, Luis R', 'Jit, Mark', 'Chen, Mark I', 'Lee, Vernon J', 'Milne, George J', 'Cook, Alex R']",Emerg Themes Epidemiol,,,True
8deca5b29c3d3c0b11f1c9032a981f95dc8d1619,PMC,Rapid Identification of Novel Immunodominant Proteins and Characterization of a Specific Linear Epitope of Campylobacter jejuni,http://dx.doi.org/10.1371/journal.pone.0065837,PMC3667084,23734261,CC BY,"Campylobacter jejuni remains one of the major gut pathogens of our time. Its zoonotic nature and wide-spread distribution in industrialized countries calls for a quick and reliable diagnostic tool. Antibody-based detection presents a suitable means to identify pathogenic bacteria. However, the knowledge about immunodominant targets is limited. Thus, an approach is presented, which allows for the rapid screening of numerous cDNA derived expression clones to identify novel antigens. The deeper understanding of immunodominant proteins assists in the design of diagnostic tools and furthers the insight into the bacterium’s pathogenicity as well as revealing potential candidates for vaccination. We have successfully screened 1536 clones of an expression library to identify 22 proteins that have not been described as immunodominant before. After subcloning the corresponding 22 genes and expression of full-length proteins, we investigated the immunodominant character by microarrays and ELISA. Subsequently, seven proteins were selected for epitope mapping. For cj0669 and cj0920c linear epitopes were identified. For cj0669, specificity assays revealed a specific linear epitope site. Consequently, an eleven amino acid residue sequence TLIKELKRLGI was analyzed via alanine scan, which revealed the glycine residue to be significant for binding of the antibody. The innovative approach presented herein of generating cDNAs of prokaryotes in combination with a microarray platform rendering time-consuming purification steps obsolete has helped to illuminate novel immunodominant proteins of C.jejuni. The findings of a specific linear epitope pave the way for a plethora of future research and the potential use in diagnostic applications such as serological screenings. Moreover, the current approach is easily adaptable to other highly relevant bacteria making it a formidable tool for the future discovery of antigens and potential biomarkers. Consequently, it is desirable to simplify the identification of structural epitopes, as this would extend the spectrum of novel epitopes to be detected.",2013 May 29,"['Hoppe, Sebastian', 'Bier, Frank F.', 'Nickisch-Rosenegk, Markus v.']",PLoS One,,,True
c5538a16c6ce27086250165a3d4ca7cbcbc3a127,PMC,Rapid Identification of Novel Immunodominant Proteins and Characterization of a Specific Linear Epitope of Campylobacter jejuni,http://dx.doi.org/10.1371/journal.pone.0065837,PMC3667084,23734261,CC BY,"Campylobacter jejuni remains one of the major gut pathogens of our time. Its zoonotic nature and wide-spread distribution in industrialized countries calls for a quick and reliable diagnostic tool. Antibody-based detection presents a suitable means to identify pathogenic bacteria. However, the knowledge about immunodominant targets is limited. Thus, an approach is presented, which allows for the rapid screening of numerous cDNA derived expression clones to identify novel antigens. The deeper understanding of immunodominant proteins assists in the design of diagnostic tools and furthers the insight into the bacterium’s pathogenicity as well as revealing potential candidates for vaccination. We have successfully screened 1536 clones of an expression library to identify 22 proteins that have not been described as immunodominant before. After subcloning the corresponding 22 genes and expression of full-length proteins, we investigated the immunodominant character by microarrays and ELISA. Subsequently, seven proteins were selected for epitope mapping. For cj0669 and cj0920c linear epitopes were identified. For cj0669, specificity assays revealed a specific linear epitope site. Consequently, an eleven amino acid residue sequence TLIKELKRLGI was analyzed via alanine scan, which revealed the glycine residue to be significant for binding of the antibody. The innovative approach presented herein of generating cDNAs of prokaryotes in combination with a microarray platform rendering time-consuming purification steps obsolete has helped to illuminate novel immunodominant proteins of C.jejuni. The findings of a specific linear epitope pave the way for a plethora of future research and the potential use in diagnostic applications such as serological screenings. Moreover, the current approach is easily adaptable to other highly relevant bacteria making it a formidable tool for the future discovery of antigens and potential biomarkers. Consequently, it is desirable to simplify the identification of structural epitopes, as this would extend the spectrum of novel epitopes to be detected.",2013 May 29,"['Hoppe, Sebastian', 'Bier, Frank F.', 'Nickisch-Rosenegk, Markus v.']",PLoS One,,,False
c0fd72cb00a30cf46c553708c2152cd09fc9f674,PMC,Metagenomic study of the viruses of African straw-coloured fruit bats: Detection of a chiropteran poxvirus and isolation of a novel adenovirus,http://dx.doi.org/10.1016/j.virol.2013.03.014,PMC3667569,23562481,CC BY,"Viral emergence as a result of zoonotic transmission constitutes a continuous public health threat. Emerging viruses such as SARS coronavirus, hantaviruses and henipaviruses have wildlife reservoirs. Characterising the viruses of candidate reservoir species in geographical hot spots for viral emergence is a sensible approach to develop tools to predict, prevent, or contain emergence events. Here, we explore the viruses of Eidolon helvum, an Old World fruit bat species widely distributed in Africa that lives in close proximity to humans. We identified a great abundance and diversity of novel herpes and papillomaviruses, described the isolation of a novel adenovirus, and detected, for the first time, sequences of a chiropteran poxvirus closely related with Molluscum contagiosum. In sum, E. helvum display a wide variety of mammalian viruses, some of them genetically similar to known human pathogens, highlighting the possibility of zoonotic transmission.",2013 Jul 5,"['Baker, Kate S.', 'Leggett, Richard M.', 'Bexfield, Nicholas H.', 'Alston, Mark', 'Daly, Gordon', 'Todd, Shawn', 'Tachedjian, Mary', 'Holmes, Clare E.G.', 'Crameri, Sandra', 'Wang, Lin-Fa', 'Heeney, Jonathan L.', 'Suu-Ire, Richard', 'Kellam, Paul', 'Cunningham, Andrew A.', 'Wood, James L.N.', 'Caccamo, Mario', 'Murcia, Pablo R.']",Virology,,,False
1acde2d851704500e78d9f3619528c43bbf3e2ba,PMC,Metagenomic study of the viruses of African straw-coloured fruit bats: Detection of a chiropteran poxvirus and isolation of a novel adenovirus,http://dx.doi.org/10.1016/j.virol.2013.03.014,PMC3667569,23562481,CC BY,"Viral emergence as a result of zoonotic transmission constitutes a continuous public health threat. Emerging viruses such as SARS coronavirus, hantaviruses and henipaviruses have wildlife reservoirs. Characterising the viruses of candidate reservoir species in geographical hot spots for viral emergence is a sensible approach to develop tools to predict, prevent, or contain emergence events. Here, we explore the viruses of Eidolon helvum, an Old World fruit bat species widely distributed in Africa that lives in close proximity to humans. We identified a great abundance and diversity of novel herpes and papillomaviruses, described the isolation of a novel adenovirus, and detected, for the first time, sequences of a chiropteran poxvirus closely related with Molluscum contagiosum. In sum, E. helvum display a wide variety of mammalian viruses, some of them genetically similar to known human pathogens, highlighting the possibility of zoonotic transmission.",2013 Jul 5,"['Baker, Kate S.', 'Leggett, Richard M.', 'Bexfield, Nicholas H.', 'Alston, Mark', 'Daly, Gordon', 'Todd, Shawn', 'Tachedjian, Mary', 'Holmes, Clare E.G.', 'Crameri, Sandra', 'Wang, Lin-Fa', 'Heeney, Jonathan L.', 'Suu-Ire, Richard', 'Kellam, Paul', 'Cunningham, Andrew A.', 'Wood, James L.N.', 'Caccamo, Mario', 'Murcia, Pablo R.']",Virology,,,False
8b112ca2f3995abd362486a677f883e402fc15da,PMC,Metagenomic study of the viruses of African straw-coloured fruit bats: Detection of a chiropteran poxvirus and isolation of a novel adenovirus,http://dx.doi.org/10.1016/j.virol.2013.03.014,PMC3667569,23562481,CC BY,"Viral emergence as a result of zoonotic transmission constitutes a continuous public health threat. Emerging viruses such as SARS coronavirus, hantaviruses and henipaviruses have wildlife reservoirs. Characterising the viruses of candidate reservoir species in geographical hot spots for viral emergence is a sensible approach to develop tools to predict, prevent, or contain emergence events. Here, we explore the viruses of Eidolon helvum, an Old World fruit bat species widely distributed in Africa that lives in close proximity to humans. We identified a great abundance and diversity of novel herpes and papillomaviruses, described the isolation of a novel adenovirus, and detected, for the first time, sequences of a chiropteran poxvirus closely related with Molluscum contagiosum. In sum, E. helvum display a wide variety of mammalian viruses, some of them genetically similar to known human pathogens, highlighting the possibility of zoonotic transmission.",2013 Jul 5,"['Baker, Kate S.', 'Leggett, Richard M.', 'Bexfield, Nicholas H.', 'Alston, Mark', 'Daly, Gordon', 'Todd, Shawn', 'Tachedjian, Mary', 'Holmes, Clare E.G.', 'Crameri, Sandra', 'Wang, Lin-Fa', 'Heeney, Jonathan L.', 'Suu-Ire, Richard', 'Kellam, Paul', 'Cunningham, Andrew A.', 'Wood, James L.N.', 'Caccamo, Mario', 'Murcia, Pablo R.']",Virology,,,False
59a34f8561b8a70870682450d318e81fc0820676,PMC,Antibody Quality and Protection from Lethal Ebola Virus Challenge in Nonhuman Primates Immunized with Rabies Virus Based Bivalent Vaccine,http://dx.doi.org/10.1371/journal.ppat.1003389,PMC3667758,23737747,CC0,"We have previously described the generation of a novel Ebola virus (EBOV) vaccine platform based on (a) replication-competent rabies virus (RABV), (b) replication-deficient RABV, or (c) chemically inactivated RABV expressing EBOV glycoprotein (GP). Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine.",2013 May 30,"['Blaney, Joseph E.', 'Marzi, Andrea', 'Willet, Mallory', 'Papaneri, Amy B.', 'Wirblich, Christoph', 'Feldmann, Friederike', 'Holbrook, Michael', 'Jahrling, Peter', 'Feldmann, Heinz', 'Schnell, Matthias J.']",PLoS Pathog,,,True
1297127819be12e7f5319edd0a9b35fd5cc566b7,PMC,An RNA Aptamer Provides a Novel Approach for the Induction of Apoptosis by Targeting the HPV16 E7 Oncoprotein,http://dx.doi.org/10.1371/journal.pone.0064781,PMC3667794,23738000,CC BY,"BACKGROUND: Human papillomavirus 16 (HPV16) is a high-risk DNA tumour virus, which is a major causative agent of cervical cancer. Cellular transformation is associated with deregulated expression of the E6 and E7 oncogenes. E7 has been shown to bind a number of cellular proteins, including the cell cycle control protein pRb. In this study, RNA aptamers (small, single-stranded oligonucleotides selected for high-affinity binding) to HPV16 E7 were employed as molecular tools to further investigate these protein-protein interactions. METHODOLOGY/PRINCIPAL FINDINGS: This study is focused on one aptamer (termed A2). Transfection of this molecule into HPV16-transformed cells resulted in inhibition of cell proliferation (shown using real-time cell electronic sensing and MTT assays) due to the induction of apoptosis (as demonstrated by Annexin V/propidium iodide staining). GST-pull down and bead binding assays were used to demonstrate that the binding of A2 required N-terminal residues of E7 known to be involved in interaction with the cell cycle control protein, pRb. Using a similar approach, A2 was shown to disrupt the interaction between E7 and pRb in vitro. Furthermore, transfection of HPV16-transformed cells with A2 appeared to result in the loss of E7 and rise in pRb levels, as observed by immunoblotting. CONCLUSIONS/SIGNIFICANCE: This paper includes the first characterisation of the effects of an E7 RNA aptamer in a cell line derived from a cervical carcinoma. Transfection of cells with A2 was correlated with the loss of E7 and the induction of apoptosis. Aptamers specific for a number of cellular and viral proteins have been documented previously; one aptamer (Macugen) is approved for clinical use and several others are in clinical trials. In addition to its role as a molecular tool, A2 could have further applications in the future.",2013 May 30,"['Nicol, Clare', 'Cesur, Özlem', 'Forrest, Sophie', 'Belyaeva, Tamara A.', 'Bunka, David H. J.', 'Blair, G. Eric', 'Stonehouse, Nicola J.']",PLoS One,,,True
20b5fc51aef8b077346c4587aad3811eebf8b11b,PMC,Monitoring Influenza Epidemics in China with Search Query from Baidu,http://dx.doi.org/10.1371/journal.pone.0064323,PMC3667820,23750192,CC BY,"Several approaches have been proposed for near real-time detection and prediction of the spread of influenza. These include search query data for influenza-related terms, which has been explored as a tool for augmenting traditional surveillance methods. In this paper, we present a method that uses Internet search query data from Baidu to model and monitor influenza activity in China. The objectives of the study are to present a comprehensive technique for: (i) keyword selection, (ii) keyword filtering, (iii) index composition and (iv) modeling and detection of influenza activity in China. Sequential time-series for the selected composite keyword index is significantly correlated with Chinese influenza case data. In addition, one-month ahead prediction of influenza cases for the first eight months of 2012 has a mean absolute percent error less than 11%. To our knowledge, this is the first study on the use of search query data from Baidu in conjunction with this approach for estimation of influenza activity in China.",2013 May 30,"['Yuan, Qingyu', 'Nsoesie, Elaine O.', 'Lv, Benfu', 'Peng, Geng', 'Chunara, Rumi', 'Brownstein, John S.']",PLoS One,,,True
574efe7771ff8495c4ace678a489b0a0869b0834,PMC,Pentraxin 3: An Immuno-Regulator in the Lungs,http://dx.doi.org/10.3389/fimmu.2013.00127,PMC3668324,23755050,CC BY,"Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that is a humoral component of the innate immune system. It interacts with pathogenic moieties, infected and dying host cells and facilitates their removal through activation of appropriate innate and adaptive mechanisms. PTX3 is secreted by a diverse variety of cells, ranging from immune cells to structural cells, in response to Toll like receptor (TLR) engagement, inflammatory stimuli, and physical and chemical stress. Further, PTX3 plays an essential role in female fertility as it facilitates the organization of extracellular matrix in the cumulus oophorus. Such activity is also implicated in post-inflammation tissue repair. PTX3 is a multifunctional protein and plays a non-redundant role in providing immunity against potential immunological dangers. Thus, we assessed its role in lung immunity, as lungs are at a constant risk of infections and tissue damage that is attributable to perpetual exposure to foreign agents.",2013 May 31,"['Balhara, Jyoti', 'Koussih, Latifa', 'Zhang, Jingbo', 'Gounni, Abdelilah Soussi']",Front Immunol,,,True
721f194d7cd4953a229e067f3e1b79ec2cf22aca,PMC,A Focused Ethnographic Study of Alberta Cattle Veterinarians’ Decision Making about Diagnostic Laboratory Submissions and Perceptions of Surveillance Programs,http://dx.doi.org/10.1371/journal.pone.0064811,PMC3669388,23741397,CC BY,"The animal and public health communities need to address the challenge posed by zoonotic emerging infectious diseases. To minimize the impacts of future events, animal disease surveillance will need to enable prompt event detection and response. Diagnostic laboratory-based surveillance systems targeting domestic animals depend in large part on private veterinarians to submit samples from cases to a laboratory. In contexts where pre-diagnostic laboratory surveillance systems have been implemented, this group of veterinarians is often asked to input data. This scenario holds true in Alberta where private cattle veterinarians have been asked to participate in the Alberta Veterinary Surveillance Network-Veterinary Practice Surveillance, a platform to which pre-diagnostic disease and non-disease case data are submitted. Consequently, understanding the factors that influence these veterinarians to submit cases to a laboratory and the complex of factors that affect their participation in surveillance programs is foundational to interpreting disease patterns reported by laboratories and engaging veterinarians in surveillance. A focused ethnographic study was conducted with ten cattle veterinarians in Alberta. Individual in-depth interviews with participants were recorded and transcribed to enable thematic analysis. Laboratory submissions were biased toward outbreaks of unknown cause, cases with unusual mortality rates, and issues with potential herd-level implications. Decreasing cattle value and government support for laboratory testing have contributed to fewer submissions over time. Participants were willing participants in surveillance, though government support and collaboration were necessary. Changes in the beef industry and veterinary profession, as well as cattle producers themselves, present both challenges and opportunities in surveillance.",2013 May 31,"['Sawford, Kate', 'Vollman, Ardene Robinson', 'Stephen, Craig']",PLoS One,,,True
09f32524e7d13409a47b77c3f7af60251df282f6,PMC,Investigation of soils affected by burnt hospital wastes in Nigeria using PIXE,http://dx.doi.org/10.1186/2193-1801-2-208,PMC3669510,23741646,CC BY,"Improper management of hospital waste has been reported to be responsible for several acute outbreaks like the severe acute respiratory syndrome (SARS). In spite of these challenges, hospital wastes are sometimes not properly handled in Nigeria. To date, there has not been an adequate study on the effect and fate of burnt hospital waste on agricultural soil. The effect of burnt hospital wastes on the agricultural soil was conducted on soils sampled around farm settlement near Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, South West Nigeria. PIXE technique was employed with a 1.7 MV 5SDH Tandem Pelletron accelerator available at Centre for Energy Research and Development O.A.U Ile-Ife, Nigeria. Eleven elements- Si, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Zr and Pb were detected and their concentrations and enrichment factors determined. The presence of Pb and Cl at the elevated concentrations range of (77.8 ± 3.5 - 279.6 ± 97.6 and 102.2 ± 37.4 -167.2±17.43) ppm respectively in this study, is of serious health concern because of the agricultural practices in the neighborhoods of the study sites. There is a need for proper handling of hospital and other related hazardous wastes because of the possibility of such posing serious environmental pollution problems.",2013 May 7,"['Ephraim P, Inyang', 'Ita, Akpan', 'Eusebius I, Obiajunwa']",Springerplus,,,True
0b180c5c5edf329811114548e19a708303e7c1c2,PMC,Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells,http://dx.doi.org/10.1371/journal.pone.0063776,PMC3670875,23755110,CC BY,"Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca(2+)) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca(2+) signaling in hPAECs by inhibiting the sarco-endoplasmic Ca(2+)-ATPase (SERCA) which is involved in the regulation of the intracellular Ca(2+) homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes.",2013 Jun 3,"['Bálint, Zoltán', 'Zabini, Diana', 'Konya, Viktoria', 'Nagaraj, Chandran', 'Végh, Attila G.', 'Váró, György', 'Wilhelm, Imola', 'Fazakas, Csilla', 'Krizbai, István A.', 'Heinemann, Akos', 'Olschewski, Horst', 'Olschewski, Andrea']",PLoS One,,,True
2d91222fa8318aa7814fe7ad58b9d97c09eb6330,PMC,The antimalarial ferroquine: from bench to clinic,http://dx.doi.org/10.1051/parasite/2011183207,PMC3671469,21894260,CC BY,"Ferroquine (FQ, SSR97193) is currently the most advanced organometallic drug candidate and about to complete phase II clinical trials as a treatment for uncomplicated malaria. This ferrocenecontaining compound is active against both chloroquine-susceptible and chloroquine-resistant Plasmodium falciparum and P. vivax strains and/or isolates. This article focuses on the discovery of FQ, its antimalarial activity, the hypothesis of its mode of action, the current absence of resistance in vitro and recent clinical trials.",2011 Aug 15,"['Biot, C.', 'Nosten, F.', 'Fraisse, L.', 'Ter-Minassian, D.', 'Khalife, J.', 'Dive, D.']",Parasite,,,True
ce387fc60565255c55785be208ae0b6b8fbb2ed3,PMC,The Pomegranate: Effects on Bacteria and Viruses That Influence Human Health,http://dx.doi.org/10.1155/2013/606212,PMC3671682,23762148,CC BY,"Pomegranates have been known for hundreds of years for their multiple health benefits, including antimicrobial activity. The recent surge in multidrug-resistant bacteria and the possibility of widespread global virus pandemics necessitate the need for additional preventative and therapeutic options to conventional drugs. Research indicates that pomegranates and their extracts may serve as natural alternatives due to their potency against a wide range of bacterial and viral pathogens. Nearly every part of the pomegranate plant has been tested for antimicrobial activities, including the fruit juice, peel, arils, flowers, and bark. Many studies have utilized pomegranate peel with success. There are various phytochemical compounds in pomegranate that have demonstrated antimicrobial activity, but most of the studies have found that ellagic acid and larger hydrolyzable tannins, such as punicalagin, have the highest activities. In some cases the combination of the pomegranate constituents offers the most benefit. The positive clinical results on pomegranate and suppression of oral bacteria are intriguing and worthy of further study. Much of the evidence for pomegranates' antibacterial and antiviral activities against foodborne pathogens and other infectious disease organisms comes from in vitro cell-based assays, necessitating further confirmation of in vivo efficacy through human clinical trials.",2013 May 20,"['Howell, Amy B.', ""D'Souza, Doris H.""]",Evid Based Complement Alternat Med,,,True
af5ac6d8e177f588034d75237f65dc8d6c0deb2f,PMC,Impact of genotype 1 and 2 of porcine reproductive and respiratory syndrome viruses on interferon-α responses by plasmacytoid dendritic cells,http://dx.doi.org/10.1186/1297-9716-44-33,PMC3672080,23675981,CC BY,"Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) infections are characterized by prolonged viremia and viral shedding consistent with incomplete immunity. Type I interferons (IFN) are essential for mounting efficient antiviral innate and adaptive immune responses, but in a recent study, North American PRRSV genotype 2 isolates did not induce, or even strongly inhibited, IFN-α in plasmacytoid dendritic cells (pDC), representing “professional IFN-α-producing cells”. Since inhibition of IFN-α expression might initiate PRRSV pathogenesis, we further characterized PRRSV effects and host modifying factors on IFN-α responses of pDC. Surprisingly, a variety of type 1 and type 2 PRRSV directly stimulated IFN-α secretion by pDC. The effect did not require live virus and was mediated through the TLR7 pathway. Furthermore, both IFN-γ and IL-4 significantly enhanced the pDC production of IFN-α in response to PRRSV exposure. PRRSV inhibition of IFN-α responses from enriched pDC stimulated by CpG oligodeoxynucleotides was weak or absent. VR-2332, the prototype genotype 2 PRRSV, only suppressed the responses by 34%, and the highest level of suppression (51%) was induced by a Chinese highly pathogenic PRRSV isolate. Taken together, these findings demonstrate that pDC respond to PRRSV and suggest that suppressive activities on pDC, if any, are moderate and strain-dependent. Thus, pDC may be a source of systemic IFN-α responses reported in PRRSV-infected animals, further contributing to the puzzling immunopathogenesis of PRRS.",2013 May 15,"['Baumann, Arnaud', 'Mateu, Enric', 'Murtaugh, Michael P', 'Summerfield, Artur']",Vet Res,,,True
70b6d8307a4bba54b599dc35cec46f521fe6f2ac,PMC,The JPC-SE Position Statement on Asbestos: A Long-Overdue Appeal by Epidemiologists to Ban Asbestos Worldwide and End Related Global Environmental Injustice,http://dx.doi.org/10.1289/ehp.1306892,PMC3673210,23635993,CC0,,2013 May 1,"Al-Delaimy, Wael K.",Environ Health Perspect,,,True
134da4eba94dc9b9f03a9244d62aee56abe0de56,PMC,A Novel Lactococcal Vaccine Expressing a Peptide from the M2 Antigen of H5N2 Highly Pathogenic Avian Influenza A Virus Prolongs Survival of Vaccinated Chickens,http://dx.doi.org/10.1155/2013/316926,PMC3674685,23766929,CC BY,"A cost-effective and efficacious influenza vaccine for use in commercial poultry farms would help protect against avian influenza outbreaks. Current influenza vaccines for poultry are expensive and subtype specific, and therefore there is an urgent need to develop a universal avian influenza vaccine. We have constructed a live bacterial vaccine against avian influenza by expressing a conserved peptide from the ectodomain of M2 antigen (M2e) on the surface of Lactococcus lactis (LL). Chickens were vaccinated intranasally with the lactococcal vaccine (LL-M2e) or subcutaneously with keyhole-limpet-hemocyanin conjugated M2e (KLH-M2e). Vaccinated and nonvaccinated birds were challenged with high pathogenic avian influenza virus A subtype H5N2. Birds vaccinated with LL-M2e or KLH-M2e had median survival times of 5.5 and 6.0 days, respectively, which were significantly longer than non-vaccinated birds (3.5 days). Birds vaccinated subcutaneously with KLH-M2e had a lower mean viral burden than either of the other two groups. However, there was a significant correlation between the time of survival and M2e-specific serum IgG. The results of these trials show that birds in both vaccinated groups had significantly (P < 0.05) higher median survival times than non-vaccinated birds and that this protection could be due to M2e-specific serum IgG.",2013 May 22,"['Reese, Kaleb A.', 'Lupfer, Christopher', 'Johnson, Rudd C.', 'Mitev, Georgi M.', 'Mullen, Valerie M.', 'Geller, Bruce L.', 'Pastey, Manoj']",Vet Med Int,,,True
4572a8588d9d97cf1aa46241f2cf9e4a4d52dab8,PMC,Nanorobot Hardware Architecture for Medical Defense,http://dx.doi.org/10.3390/s8052932,PMC3675524,27879858,CC BY,"This work presents a new approach with details on the integrated platform and hardware architecture for nanorobots application in epidemic control, which should enable real time in vivo prognosis of biohazard infection. The recent developments in the field of nanoelectronics, with transducers progressively shrinking down to smaller sizes through nanotechnology and carbon nanotubes, are expected to result in innovative biomedical instrumentation possibilities, with new therapies and efficient diagnosis methodologies. The use of integrated systems, smart biosensors, and programmable nanodevices are advancing nanoelectronics, enabling the progressive research and development of molecular machines. It should provide high precision pervasive biomedical monitoring with real time data transmission. The use of nanobioelectronics as embedded systems is the natural pathway towards manufacturing methodology to achieve nanorobot applications out of laboratories sooner as possible. To demonstrate the practical application of medical nanorobotics, a 3D simulation based on clinical data addresses how to integrate communication with nanorobots using RFID, mobile phones, and satellites, applied to long distance ubiquitous surveillance and health monitoring for troops in conflict zones. Therefore, the current model can also be used to prevent and save a population against the case of some targeted epidemic disease.",2008 May 6,"['Cavalcanti, Adriano', 'Shirinzadeh, Bijan', 'Zhang, Mingjun', 'Kretly, Luiz C.']",Sensors (Basel),,,True
955cb107f58aff48a58de2473c2fe04e42bfa1e3,PMC,Self-Oligomerization Is Essential for Enhanced Immunological Activities of Soluble Recombinant Calreticulin,http://dx.doi.org/10.1371/journal.pone.0064951,PMC3677884,23762269,CC BY,"We have recently reported that calreticulin (CRT), a luminal resident protein, can be found in the sera of patients with rheumatoid arthritis and also that recombinant CRT (rCRT) exhibits extraordinarily strong immunological activities. We herein further demonstrate that rCRT fragments 18–412 (rCRT/18-412), rCRT/39-272, rCRT/120-308 and rCRT/120-250 can self-oligomerize in solution and are 50–100 fold more potent than native CRT (nCRT, isolated from mouse livers) in activating macrophages in vitro. We narrowed down the active site of CRT to residues 150–230, the activity of which also depends on dimerization. By contrast, rCRT/18-197 is almost completely inactive. When rCRT/18-412 is fractionated into oligomers and monomers by gel filtration, the oligomers maintain most of their immunological activities in terms of activating macrophages in vitro and inducing specific antibodies in vivo, while the monomers were much less active by comparison. Additionally, rCRT/18-412 oligomers are much better than monomers in binding to, and uptake by, macrophages. Inhibition of macrophage endocytosis partially blocks the stimulatory effect of rCRT/18-412. We conclude that the immunologically active site of CRT maps between residues 198–230 and that soluble CRT could acquire potent immuno-pathological activities in microenvironments favoring its oligomerization.",2013 Jun 10,"['Huang, Shang-Hui', 'Zhao, Li-Xiang', 'Hong, Chao', 'Duo, Cui-Cui', 'Guo, Bing-Nan', 'Zhang, Li-Juan', 'Gong, Zheng', 'Xiong, Si-Dong', 'Gong, Fang-Yuan', 'Gao, Xiao-Ming']",PLoS One,,,True
05513568bb7b58bb7df33023160838ac885a6144,PMC,Coalescent inference for infectious disease: meta-analysis of hepatitis C,http://dx.doi.org/10.1098/rstb.2012.0314,PMC3678333,23382432,CC BY,"Genetic analysis of pathogen genomes is a powerful approach to investigating the population dynamics and epidemic history of infectious diseases. However, the theoretical underpinnings of the most widely used, coalescent methods have been questioned, casting doubt on their interpretation. The aim of this study is to develop robust population genetic inference for compartmental models in epidemiology. Using a general approach based on the theory of metapopulations, we derive coalescent models under susceptible–infectious (SI), susceptible–infectious–susceptible (SIS) and susceptible–infectious–recovered (SIR) dynamics. We show that exponential and logistic growth models are equivalent to SI and SIS models, respectively, when co-infection is negligible. Implementing SI, SIS and SIR models in BEAST, we conduct a meta-analysis of hepatitis C epidemics, and show that we can directly estimate the basic reproductive number (R(0)) and prevalence under SIR dynamics. We find that differences in genetic diversity between epidemics can be explained by differences in underlying epidemiology (age of the epidemic and local population density) and viral subtype. Model comparison reveals SIR dynamics in three globally restricted epidemics, but most are better fit by the simpler SI dynamics. In summary, metapopulation models provide a general and practical framework for integrating epidemiology and population genetics for the purposes of joint inference.",2013 Mar 19,"['Dearlove, Bethany', 'Wilson, Daniel J.']",Philos Trans R Soc Lond B Biol Sci,,,True
808eb805948a72da00d370c274656653679536b5,PMC,"Epitope Mapping of M36, a Human Antibody Domain with Potent and Broad HIV-1 Inhibitory Activity",http://dx.doi.org/10.1371/journal.pone.0066638,PMC3679054,23776690,CC BY,"M36 is the first member of a novel class of potent HIV-1 entry inhibitors based on human engineered antibody domains (eAds). It exhibits broad inhibitory activity suggesting that its CD4-induced epitope is highly conserved. Here, we describe fine mapping of its epitope by using several approaches. First, a panel of mimotopes was affinity-selected from a random peptide library and potential m36-binding residues were computationally predicted. Second, homology modeling of m36 and molecular docking of m36 onto gp120 revealed potentially important residues in gp120-m36 interactions. Third, the predicted contact residues were verified by site-directed mutagenesis. Taken together, m36 epitope comprising three discontinuous sites including six key gp120 residues (Site C1: Thr123 and Pro124; Site C3: Glu370 and Ile371; Site C4: Met426 and Trp427) were identified. In the 3D structure of gp120, the sites C1 and C4 are located in the bridging sheet and the site C3 is within the β15-α3 excursion, which play essential roles for the receptor- and coreceptor-binding and are major targets of neutralizing antibodies. Based on these results we propose a precise localization of the m36 epitope and suggest a mechanism of its broad inhibitory activity which could help in the development of novel HIV-1 therapeutics based on eAds.",2013 Jun 11,"['Wan, Chao', 'Sun, Jianping', 'Chen, Weizao', 'Yuan, Xiaohui', 'Chong, Huihui', 'Prabakaran, Ponraj', 'Dimitrov, Dimiter S.', 'He, Yuxian']",PLoS One,,,True
e3de6d6d50592102725cbe2ee5cb0fe02b851aac,PMC,Inhibitory Effect of Resveratrol against Duck Enteritis Virus In Vitro,http://dx.doi.org/10.1371/journal.pone.0065213,PMC3679110,23776451,CC BY,"Duck viral enteritis (DVE) is an acute, contagious herpesvirus infection of ducks, geese, and swans of all ages and species. This disease has been responsible for significant economic losses in domestic and wild waterfowl as a result of mortality, and decreased egg production. Resveratrol is a naturally occurring phytoalexin in specific plants and exhibits inhibitory activity against many kinds of virus. In this paper, resveratrol was found to inhibit duck enteritis virus (DEV) replication in a dose-dependent manner, with a 50% inhibition concentration of 3.85 μg/mL. The inhibition in virus multiplication in the presence of resveratrol was not attributed to direct inactivation or inhibition of virus attachment to the host cells, but to the inhibition of viral multiplication in host cells. The assay of the time of addition limited the drug effect during the first 8 h of infection. This conclusion was supported by the ultrastructure images of the early stage of DEV infection, which showed that the replication of virus nucleic acid and the formation of the capsid in the cell nucleus were suppressed. In the indirect immunofluorescence assay, proteins expression in DEV infected duck embryo fibroblasts (DEFs) within 24 h post-infection (p.i.) was also effectively suppressed by resveratrol. In summary, the resveratrol has a good activity against DEV infection in vitro, which could be attributed to that fact that several essential immediate early viral proteins for virus replication were impacted by resveratrol.",2013 Jun 11,"['Xu, Jiao', 'Yin, Zhongqiong', 'Li, Li', 'Cheng, Anchun', 'Jia, Renyong', 'Song, Xu', 'Lu, Hongke', 'Dai, Shujun', 'Lv, Cheng', 'Liang, Xiaoxia', 'He, Changliang', 'Zhao, Ling', 'Su, Gang', 'Ye, Gang', 'Shi, Fei']",PLoS One,,,True
c9d84fcde35a82c200f779df24657558638bf40b,PMC,Fading vision: knowledge translation in the implementation of a public health policy intervention,http://dx.doi.org/10.1186/1748-5908-8-59,PMC3680003,23734672,CC BY,"BACKGROUND: In response to several high profile public health crises, public health renewal is underway in Canada. In the province of British Columbia, the Ministry of Health initiated a collaborative evidence-informed process involving a steering committee of representatives from the six health authorities. A Core Functions (CF) Framework was developed, identifying 21 core public health programs. For each core program, an evidence review was conducted and a model core program paper developed. These documents were distributed to health authorities to guide development of their own renewed public health services. The CF implementation was conceptualized as an embedded knowledge translation process. A CF coordinator in each health authority was to facilitate a gap analysis and development of a performance improvement plan for each core program, and post these publically on the health authority website. METHODS: Interviews (n = 19) and focus groups (n = 8) were conducted with a total of 56 managers and front line staff from five health authorities working in the Healthy Living and Sexually Transmitted Infection Prevention core programs. All interviews and focus groups were digitally recorded, transcribed and verified by the project coordinator. Five members of the research team used NVivo 9 to manage data and conducted a thematic analysis. RESULTS: Four main themes emerged concerning implementation of the CF Framework generally, and the two programs specifically. The themes were: ‘you’ve told me what, now tell me how’; ‘the double bind’; ‘but we already do that’; and the ‘selling game.’ Findings demonstrate the original vision of the CF process was lost in the implementation process and many participants were unaware of the CF framework or process. CONCLUSIONS: Results are discussed with respect to a well-known framework on the adoption, assimilation, and implementation of innovations in health services organizations. Despite attempts of the Ministry of Health and the Steering Committee to develop and implement a collaborative, evidence-informed policy intervention, there were several barriers to the realization of the vision for core public health functions implementation, at least in the early stages. In neglecting the implementation process, it seems unlikely that the expected benefits of the public health renewal process will be realized.",2013 Jun 4,"['Tomm-Bonde, Laura', 'Schreiber, Rita S', 'Allan, Diane E', 'MacDonald, Marjorie', 'Pauly, Bernie', 'Hancock, Trevor']",Implement Sci,,,True
dec25863e871c025ecfd92611e727196ae88cb5b,PMC,Introducing the Outbreak Threshold in Epidemiology,http://dx.doi.org/10.1371/journal.ppat.1003277,PMC3680036,23785276,CC BY,"When a pathogen is rare in a host population, there is a chance that it will die out because of stochastic effects instead of causing a major epidemic. Yet no criteria exist to determine when the pathogen increases to a risky level, from which it has a large chance of dying out, to when a major outbreak is almost certain. We introduce such an outbreak threshold (T(0)), and find that for large and homogeneous host populations, in which the pathogen has a reproductive ratio R(0), on the order of 1/Log(R(0)) infected individuals are needed to prevent stochastic fade-out during the early stages of an epidemic. We also show how this threshold scales with higher heterogeneity and R(0) in the host population. These results have implications for controlling emerging and re-emerging pathogens.",2013 Jun 6,"['Hartfield, Matthew', 'Alizon, Samuel']",PLoS Pathog,,,True
7ddadb59be0e7a80bfe88d3ff35c41d261c7a9b0,PMC,Introducing the Outbreak Threshold in Epidemiology,http://dx.doi.org/10.1371/journal.ppat.1003277,PMC3680036,23785276,CC BY,"When a pathogen is rare in a host population, there is a chance that it will die out because of stochastic effects instead of causing a major epidemic. Yet no criteria exist to determine when the pathogen increases to a risky level, from which it has a large chance of dying out, to when a major outbreak is almost certain. We introduce such an outbreak threshold (T(0)), and find that for large and homogeneous host populations, in which the pathogen has a reproductive ratio R(0), on the order of 1/Log(R(0)) infected individuals are needed to prevent stochastic fade-out during the early stages of an epidemic. We also show how this threshold scales with higher heterogeneity and R(0) in the host population. These results have implications for controlling emerging and re-emerging pathogens.",2013 Jun 6,"['Hartfield, Matthew', 'Alizon, Samuel']",PLoS Pathog,,,False
3498e7e96b742565d9041107cae12e667b394f9f,PMC,Transcription analysis of the porcine alveolar macrophage response to porcine circovirus type 2,http://dx.doi.org/10.1186/1471-2164-14-353,PMC3680065,23711280,CC BY,"BACKGROUND: Porcine circovirus type 2 (PCV2) is the causal agent of postweaning multisystemic wasting syndrome (PMWS), which has severely impacted the swine industry worldwide. PCV2 triggers a weak and atypical innate immune response, but the key genes and mechanisms by which the virus interferes with host innate immunity have not yet been elucidated. In this study, genes that control the response of primary porcine alveolar macrophages (PAMs), the main target of PCV2, were profiled in vitro. RESULTS: PAMs were successfully infected by PCV2-WH strain, as evidenced quantitative real-time polymerase chain reaction (qPCR) and immunofluorescence assay (IFA) results. Infection-related differential gene expression was investigated using pig microarrays from the US Pig Genome Coordination Program and validated by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Microarray analysis at 24 and 48 hours post-infection (HPI) revealed 266 and 175 unique genes, respectively, that were differentially expressed (false discovery rate <0.05; fold-change >2). Only six genes were differentially expressed between 24 and 48 HPI. The up-regulated genes were principally related to immune response, cytokine activity, locomotion, regulation of cell proliferation, apoptosis, cell growth arrest, and antigen procession and presentation. The down-regulated genes were mainly involved in terpenoid biosynthesis, carbohydrate metabolism, translation, proteasome degradation, signal transducer activity, and ribosomal proteins, which were representative of the reduced vital activity of PCV2-infected cells. CONCLUSIONS: PCV2 infection of PAMs causes up-regulation of genes related to inflammation, indicating that PCV2 may induce systematic inflammation. PCV2 persistently induced cytokines, mainly through the Toll-like receptor (TLR) 1 and TLR9 pathways, which may promote high levels of cytokine secretion. PCV2 may prevent apoptosis in PAMs by up-regulating SERPINB9 expression, possibly to lengthen the duration of PCV2 replication-permissive conditions. The observed gene expression profile may provide insights into the underlying immunological response and pathological changes that occur in pigs following PCV2 infection.",2013 May 27,"['Li, Wentao', 'Liu, Shuqing', 'Wang, Yang', 'Deng, Feng', 'Yan, Weidong', 'Yang, Kun', 'Chen, Huanchun', 'He, Qigai', 'Charreyre, Catherine', 'Audoneet, Jean-Christophe']",BMC Genomics,,,True
b6e8f6a447550c5a8d3581adfffb225e8b59fe43,PMC,Identification of canine parvovirus with the Q370R point mutation in the VP2 gene from a giant panda (Ailuropoda melanoleuca),http://dx.doi.org/10.1186/1743-422X-10-163,PMC3680276,23706032,CC BY,"BACKGROUND: In this study, we sequenced and phylogenetic analyses of the VP2 genes from twelve canine parvovirus (CPV) strains obtained from eleven domestic dogs and a giant panda (Ailuropoda melanoleuca) in China. A novel canine parvovirus (CPV) was detected from the giant panda in China. RESULTS: Nucleotide and phylogenetic analysis of the capsid protein VP2 gene classified the CPV as a new CPV-2a type. Substitution of Gln for Arg at the conserved 370 residue in CPV presents an unusual variation in the new CPV-2a amino acid sequence of the giant panda and is further evidence for the continuing evolution of the virus. CONCLUSIONS: These findings extend the knowledge on CPV molecular epidemiology of particular relevance to wild carnivores.",2013 May 26,"['Guo, Ling', 'Yang, Shao-lin', 'Chen, Shi-jie', 'Zhang, Zhihe', 'Wang, Chengdong', 'Hou, Rong', 'Ren, Yupeng', 'wen, Xintian', 'Cao, Sanjie', 'Guo, Wanzhu', 'Hao, Zhongxiang', 'Quan, Zifang', 'Zhang, Manli', 'Yan, Qi-gui']",Virol J,,,True
339f0cd12ca08506c22c8b62eb4b3283a437271a,PMC,Correlation between Dengue-Specific Neutralizing Antibodies and Serum Avidity in Primary and Secondary Dengue Virus 3 Natural Infections in Humans,http://dx.doi.org/10.1371/journal.pntd.0002274,PMC3681624,23785536,CC BY,"Although heterotypic secondary infection with dengue virus (DENV) is associated with severe disease, the majority of secondary infections are mild or asymptomatic. The mechanisms of antibody-mediated protection are poorly understood. In 2010, 108 DENV3-positive cases were enrolled in a pediatric hospital-based study in Managua, Nicaragua, with 61 primary and 47 secondary infections. We analyzed DENV-specific neutralization titers (NT(50)), IgM and IgG avidity, and antibody titer in serum samples collected during acute and convalescent phases and 3, 6, and 18 months post-infection. NT(50) titers peaked at convalescence and decreased thereafter. IgG avidity to DENV3 significantly increased between convalescent and 3-month time-points in primary DENV infections and between the acute and convalescent phase in secondary DENV infections. While avidity to DENV2, a likely previous infecting serotype, was initially higher than avidity to DENV3 in secondary DENV infections, the opposite relation was observed 3–18 months post-infection. We found significant correlations between IgM avidity and NT(50) in acute primary cases and between IgG avidity and NT(50) in secondary DENV infections. In summary, our findings indicate that IgM antibodies likely play a role in early control of DENV infections. IgG serum avidity to DENV, analyzed for the first time in longitudinal samples, switches from targeting mainly cross-reactive serotype(s) to the current infecting serotype over time. Finally, serum avidity correlates with neutralization capacity.",2013 Jun 13,"['Puschnik, Andreas', 'Lau, Louis', 'Cromwell, Elizabeth A.', 'Balmaseda, Angel', 'Zompi, Simona', 'Harris, Eva']",PLoS Negl Trop Dis,,,True
8b11ed8edd1f59ac713ddcc3282ad5a98b8b68b7,PMC,Efficient Sensing of Infected Cells in Absence of Virus Particles by Blasmacytoid Dendritic Cells Is Blocked by the Viral Ribonuclease E(rns),http://dx.doi.org/10.1371/journal.ppat.1003412,PMC3681750,23785283,CC BY,"Plasmacytoid dendritic cells (pDC) have been shown to efficiently sense HCV- or HIV-infected cells, using a virion-free pathway. Here, we demonstrate for classical swine fever virus, a member of the Flaviviridae, that this process is much more efficient in terms of interferon-alpha induction when compared to direct stimulation by virus particles. By employment of virus replicon particles or infectious RNA which can replicate but not form de novo virions, we exclude a transfer of virus from the donor cell to the pDC. pDC activation by infected cells was mediated by a contact-dependent RNA transfer to pDC, which was sensitive to a TLR7 inhibitor. This was inhibited by drugs affecting the cytoskeleton and membrane cholesterol. We further demonstrate that a unique viral protein with ribonuclease activity, the viral E(rns) protein of pestiviruses, efficiently prevented this process. This required intact ribonuclease function in intracellular compartments. We propose that this pathway of activation could be of particular importance for viruses which tend to be mostly cell-associated, cause persistent infection, and are non-cytopathogenic.",2013 Jun 13,"['Python, Sylvie', 'Gerber, Markus', 'Suter, Rolf', 'Ruggli, Nicolas', 'Summerfield, Artur']",PLoS Pathog,,,True
3bad4716622640d66aad1bf65067abc5b5a2cb01,PMC,"Different Immunity Elicited by Recombinant H5N1 Hemagglutinin Proteins Containing Pauci-Mannose, High-Mannose, or Complex Type N-Glycans",http://dx.doi.org/10.1371/journal.pone.0066719,PMC3682957,23799128,CC BY,"Highly pathogenic avian influenza H5N1 viruses can result in poultry and occasionally in human mortality. A safe and effective H5N1 vaccine is urgently needed to reduce the pandemic potential. Hemagglutinin (HA), a major envelope protein accounting for approximately 80% of spikes in influenza virus, is often used as a major antigen for subunit vaccine development. In this study, we conducted a systematic study of the immune response against influenza virus infection following immunization with recombinant HA proteins expressed in insect (Sf9) cells, insect cells that contain exogenous genes for elaborating N-linked glycans (Mimic) and mammalian cells (CHO). While the antibody titers are higher with the insect cell derived HA proteins, the neutralization and HA inhibition titers are much higher with the mammalian cell produced HA proteins. Recombinant HA proteins containing tri- or tetra-antennary complex, terminally sialylated and asialyated-galactose type N-glycans induced better protective immunity in mice to lethal challenge. The results are highly relevant to issues that should be considered in the production of fragment vaccines.",2013 Jun 14,"['Lin, Shih-Chang', 'Jan, Jia-Tsrong', 'Dionne, Ben', 'Butler, Michael', 'Huang, Ming-Hsi', 'Wu, Chung-Yi', 'Wong, Chi-Huey', 'Wu, Suh-Chin']",PLoS One,,,True
44676dd185a852b134c04a333d31b7e081f419f0,PMC,Sumoylation at the Host-Pathogen Interface,http://dx.doi.org/10.3390/biom2020203,PMC3685863,23795346,CC BY,"Many viral proteins have been shown to be sumoylated with corresponding regulatory effects on their protein function, indicating that this host cell modification process is widely exploited by viral pathogens to control viral activity. In addition to using sumoylation to regulate their own proteins, several viral pathogens have been shown to modulate overall host sumoylation levels. Given the large number of cellular targets for SUMO addition and the breadth of critical cellular processes that are regulated via sumoylation, viral modulation of overall sumoylation presumably alters the cellular environment to ensure that it is favorable for viral reproduction and/or persistence. Like some viruses, certain bacterial plant pathogens also target the sumoylation system, usually decreasing sumoylation to disrupt host anti-pathogen responses. The recent demonstration that Listeria monocytogenes also disrupts host sumoylation, and that this is required for efficient infection, extends the plant pathogen observations to a human pathogen and suggests that pathogen modulation of host sumoylation may be more widespread than previously appreciated. This review will focus on recent aspects of how pathogens modulate the host sumoylation system and how this benefits the pathogen.",2012 Apr 5,"Wilson, Van G.",Biomolecules,,,True
78330b92514605d59bb22b99c517538f83c2e2b7,PMC,Evaluation and molecular characterization of human adenovirus in drinking water supplies: viral integrity and viability assays,http://dx.doi.org/10.1186/1743-422X-10-166,PMC3686584,23714224,CC BY,"BACKGROUND: Human adenoviruses (HAdVs) are the second-leading cause of childhood gastroenteritis worldwide. This virus is commonly found in environmental waters and is very resistant to water disinfection and environmental stressors, especially UV light inactivation. Molecular techniques, such as PCR-based methods (Polymerase Chain Reaction), are commonly used to detect and identify viral contamination in water, although PCR alone does not allow the discrimination between infectious and non-infectious viral particles. A combination of cell culture and PCR has allowed detection of infectious viruses that grow slowly or fail to produce cytopathic effects (CPE) in cell culture. This study aimed to assess the integrity and viability of human adenovirus (HAdV) in environmental water and evaluate circulating strains by molecular characterization in three sites of the water supply in Florianópolis, Santa Catarina Island, Brazil: Peri Lagoon water, spring source water, and water from the public water supply system. METHODS: Water samples were collected, concentrated and HAdV quantified by real-time PCR. Viral integrity was evaluated by enzymatic assay (DNase I) and infectivity by plaque assay (PA) and integrated cell culture using transcribed mRNA (ICC-RT-qPCR). Samples containing particles of infectious HAdV were selected for sequencing and molecular characterization. RESULTS: The analyzed sites contained 83, 66 and 58% undamaged HAdV particles (defined as those in which the genetic material is protected by the viral capsid) at Peri Lagoon, spring source water and public supply system water, respectively. Of these, 66% of the particles (by PA) and 75% (by ICC-RT-qPCR) HAdV were shown to be infectious, due to being undamaged in Peri Lagoon, 33% (by PA) and 58% (by ICC-RT-qPCR) in spring source water and 8% (by PA) and 25% (by ICC-RT-qPCR) in the public water supply system. ICC-RT-qPCR, a very sensitive and rapid technique, was able to detect as low as 1 × 10(2) HAdV genome copies per milliliter of infectious viral particles in the environmental water samples. The molecular characterization studies indicated that HAdV-2 was the prevalent serotype. CONCLUSIONS: These results indicate a lack of proper public health measures. We suggest that HAdV can be efficiently used as a marker of environmental and drinking water contamination and ICC-RT-qPCR demonstrated greater sensitivity and speed of detection of infectious viral particles compared to PA.",2013 May 28,"['Fongaro, Gislaine', 'Nascimento, Mariana A do', 'Rigotto, Caroline', 'Ritterbusch, Giseli', 'da Silva, Alessandra D’ A', 'Esteves, Paulo A', 'Barardi, Célia R M']",Virol J,,,True
56f33cfd84beba69ee9c4c24da6f4840871ae679,PMC,P042: Severe influenza infections requiring intensive care during winter 2012/2013,http://dx.doi.org/10.1186/2047-2994-2-S1-P42,PMC3688439,,CC BY,,2013 Jun 20,"['Landelle, C', 'Iten, A', 'Kaiser, L', 'Thomas, Y', 'Genevois, E', 'Joubert, D', 'Richard, J-C', 'Harbarth, S', 'Pittet, D', 'Brochard, L']",Antimicrob Resist Infect Control,,,False
ca0c911ee3620b7acdb37a5b5d0b500128205f32,PMC,Evidence for Novel Hepaciviruses in Rodents,http://dx.doi.org/10.1371/journal.ppat.1003438,PMC3688547,23818848,CC BY,"Hepatitis C virus (HCV) is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma. Research is complicated by a lack of accessible small animal models. The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology. We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 rodents (41 species); and sera from 2,939 bats (51 species). Three highly divergent rodent hepacivirus clades were detected in 27 (1.8%) of 1,465 European bank voles (Myodes glareolus) and 10 (1.9%) of 518 South African four-striped mice (Rhabdomys pumilio). Bats showed anti-HCV immunoblot reactivities but no virus detection, although the genetic relatedness suggested by the serologic results should have enabled RNA detection using the broadly reactive PCR assays developed for this study. 210 horses and 858 cats and dogs were tested, yielding further horse-associated hepaciviruses but none in dogs or cats. The rodent viruses were equidistant to HCV, exceeding by far the diversity of HCV and the canine/equine hepaciviruses taken together. Five full genomes were sequenced, representing all viral lineages. Salient genome features and distance criteria supported classification of all viruses as hepaciviruses. Quantitative RT-PCR, RNA in-situ hybridisation, and histopathology suggested hepatic tropism with liver inflammation resembling hepatitis C. Recombinant serology for two distinct hepacivirus lineages in 97 bank voles identified seroprevalence rates of 8.3 and 12.4%, respectively. Antibodies in bank vole sera neither cross-reacted with HCV, nor the heterologous bank vole hepacivirus. Co-occurrence of RNA and antibodies was found in 3 of 57 PCR-positive bank vole sera (5.3%). Our data enable new hypotheses regarding HCV evolution and encourage efforts to develop rodent surrogate models for HCV.",2013 Jun 20,"['Drexler, Jan Felix', 'Corman, Victor Max', 'Müller, Marcel Alexander', 'Lukashev, Alexander N.', 'Gmyl, Anatoly', 'Coutard, Bruno', 'Adam, Alexander', 'Ritz, Daniel', 'Leijten, Lonneke M.', 'van Riel, Debby', 'Kallies, Rene', 'Klose, Stefan M.', 'Gloza-Rausch, Florian', 'Binger, Tabea', 'Annan, Augustina', 'Adu-Sarkodie, Yaw', 'Oppong, Samuel', 'Bourgarel, Mathieu', 'Rupp, Daniel', 'Hoffmann, Bernd', 'Schlegel, Mathias', 'Kümmerer, Beate M.', 'Krüger, Detlev H.', 'Schmidt-Chanasit, Jonas', 'Setién, Alvaro Aguilar', 'Cottontail, Veronika M.', 'Hemachudha, Thiravat', 'Wacharapluesadee, Supaporn', 'Osterrieder, Klaus', 'Bartenschlager, Ralf', 'Matthee, Sonja', 'Beer, Martin', 'Kuiken, Thijs', 'Reusken, Chantal', 'Leroy, Eric M.', 'Ulrich, Rainer G.', 'Drosten, Christian']",PLoS Pathog,,,True
a523dca1cc7a585e2433acb959f3d396f35b9c79,PMC,"Risk Factors for Infectious Diseases in Backyard Poultry Farms in the Poyang Lake Area, China",http://dx.doi.org/10.1371/journal.pone.0067366,PMC3688663,23840680,CC BY,"Emergence and transmission of infectious diseases have an enormous impact on the poultry industry and present a serious threat to the health of humans and wild birds. Noncommercial poultry operations, such as backyard poultry facilities in China, are potential sources of virus exchange between commercial poultry and wild birds. It is particularly critical in wetland areas where backyard poultry have close contact with commercial poultry and migratory birds, therefore increasing the risk of contracting infectious diseases. To evaluate the transmission risks, a cross-sectional study was undertaken in the Poyang Lake area, China, involving 309 residents in the backyard poultry farms in three counties (Region A, B, and C) of Jiangxi Province. We examined the backyard poultry population, poultry species, presence of poultry deaths from infectious diseases, food sources, and biosecurity practices. Region B ranked highest for biosecurity while region C ranked lowest. The risks of infectious diseases were assessed by adjusted odds ratio based on multivariate logistic regression analysis. Potential risk factors in the three regions of the study site were compared. In Region A, significant factor was contact of poultry with wild birds (OR: 6.573, 95% CI: 2.148–20.115, P=0.001). In Region B, the most significant factor was contact of poultry with neighboring backyard waterfowls (OR: 3.967, 95% CI: 1.555–10.122, P=0.004). In Region C, significant factors were poultry purchase from local live bird markets (OR: 3.740, 95% CI: 1.243–11.255, P=0.019), and contact of poultry with wild birds (OR: 3.379, 95% CI: 1.058–10.791, P=0.040). In summary, backyard poultry was significantly affected by neighboring commercial poultry and close contact with wild birds. The results are expected to improve our understanding of the transmission risks of infectious diseases in a typical backyard poultry environment in rural China, and address the need to improve local farming practices and take preventive measures.",2013 Jun 20,"['Wang, Yong', 'Jiang, Zhiben', 'Jin, Zhenyu', 'Tan, Hua', 'Xu, Bing']",PLoS One,,,True
6fb874a7dee1d36545f8ea3c9714b288dca736e4,PMC,Rapid Generation of Human-Like Neutralizing Monoclonal Antibodies in Urgent Preparedness for Influenza Pandemics and Virulent Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0066276,PMC3688872,23824680,CC BY,"BACKGROUND: The outbreaks of emerging infectious diseases caused by pathogens such as SARS coronavirus, H5N1, H1N1, and recently H7N9 influenza viruses, have been associated with significant mortality and morbidity in humans. Neutralizing antibodies from individuals who have recovered from an infection confer therapeutic protection to others infected with the same pathogen. However, survivors may not always be available for providing plasma or for the cloning of monoclonal antibodies (mAbs). METHODOLOGY/PRINCIPAL FINDINGS: The genome and the immunoglobulin genes in rhesus macaques and humans are highly homologous; therefore, we investigated whether neutralizing mAbs that are highly homologous to those of humans (human-like) could be generated. Using the H5N1 influenza virus as a model, we first immunized rhesus macaques with recombinant adenoviruses carrying a synthetic gene encoding hemagglutinin (HA). Following screening an antibody phage display library derived from the B cells of immunized monkeys, we cloned selected macaque immunoglobulin heavy chain and light chain variable regions into the human IgG constant region, which generated human-macaque chimeric mAbs exhibiting over 97% homology to human antibodies. Selected mAbs demonstrated potent neutralizing activities against three clades (0, 1, 2) of the H5N1 influenza viruses. The in vivo protection experiments demonstrated that the mAbs effectively protected the mice even when administered up to 3 days after infection with H5N1 influenza virus. In particular, mAb 4E6 demonstrated sub-picomolar binding affinity to HA and superior in vivo protection efficacy without the loss of body weight and obvious lung damage. The analysis of the 4E6 escape mutants demonstrated that the 4E6 antibody bound to a conserved epitope region containing two amino acids on the globular head of HA. CONCLUSIONS/SIGNIFICANCE: Our study demonstrated the generation of neutralizing mAbs for potential application in humans in urgent preparedness against outbreaks of new influenza infections or other virulent infectious diseases.",2013 Jun 18,"['Meng, Weixu', 'Pan, Weiqi', 'Zhang, Anna J. X.', 'Li, Zhengfeng', 'Wei, Guowei', 'Feng, Liqiang', 'Dong, Zhenyuan', 'Li, Chufang', 'Hu, Xiangjing', 'Sun, Caijun', 'Luo, Qinfang', 'Yuen, Kwok-Yung', 'Zhong, Nanshan', 'Chen, Ling']",PLoS One,,,True
11a3797796973b32b0763f8127b908f4783e5734,PMC,Comprehensive Mapping Antigenic Epitopes of NS1 Protein of Japanese Encephalitis Virus with Monoclonal Antibodies,http://dx.doi.org/10.1371/journal.pone.0067553,PMC3688998,23825668,CC BY,"Japanese encephalitis virus (JEV) non-structural protein 1 (NS1) contributes to virus replication and elicits protective immune responses during infection. JEV NS1-specific antibody responses could be a target in the differential diagnosis of different flavivirus infections. However, the epitopes on JEV NS1 are poorly characterized. The present study describes the full mapping of linear B-cell epitopes in JEV NS1. We generated eleven NS1-specific monoclonal antibodies from mice immunized with recombinant NS1. For epitope mapping of monoclonal antibodies, a set of 51 partially-overlapping peptides covering the entire NS1 protein were expressed with a GST-tag and then screened using monoclonal antibodies. Through enzyme-linked immunosorbent assay (ELISA), five linear epitope-containing peptides were identified. By sequentially removing amino acid residues from the carboxy and amino terminal of peptides, the minimal units of the five linear epitopes were identified and confirmed using monoclonal antibodies. Five linear epitopes are located in amino acids residues (5)AIDITRK(11), (72)RDELNVL(78), (251)KSKHNRREGY(260), (269)DENGIVLD(276), and (341)DETTLVRS(348). Furthermore, it was found that the epitopes are highly conserved among JEV strains through sequence alignment. Notably, none of the homologous regions on NS1 proteins from other flaviviruses reacted with the MAbs when they were tested for cross-reactivity, and all five epitope peptides were not recognized by sera against West Nile virus or Dengue virus. These novel virus-specific linear B-cell epitopes of JEV NS1 would benefit the development of new vaccines and diagnostic assays.",2013 Jun 18,"['Hua, Rong-Hong', 'Liu, Li-Ke', 'Chen, Zhen-Shi', 'Li, Ye-Nan', 'Bu, Zhi-Gao']",PLoS One,,,True
5ef424a39823c1e6a0fc472b7ed744121356f11d,PMC,Multiantibody Strategies for HIV,http://dx.doi.org/10.1155/2013/632893,PMC3690221,23840243,CC BY,"Vaccination strategies depend entirely on the appropriate responsiveness of our immune system against particular antigens. For this active immunization to be truly effective, neutralizing antibodies (nAbs) need to efficiently counter the infectivity or propagation of the pathogen. Some viruses, including HIV, are able to take advantage of this immune response in order to evade nAbs. This review focuses on viral immune evasion strategies that result directly from a robust immune response to infection or vaccination. A rationale for multi-Ab therapy to circumvent this phenomenon is discussed. Progress in the formulation, production, and regulatory approval of monoclonal antibodies (mAbs) is presented.",2013 Jun 6,"['Hiatt, Andrew', 'Zeitlin, Larry', 'Whaley, Kevin J.']",Clin Dev Immunol,,,True
9c59d3a8be1e640d85fc5105dca9e530680c230a,PMC,"Knowledge Levels and Training Needs of Disaster Medicine among Health Professionals, Medical Students, and Local Residents in Shanghai, China",http://dx.doi.org/10.1371/journal.pone.0067041,PMC3691157,23826190,CC BY,"BACKGROUND: Disaster is a serious public health issue. Health professionals and community residents are main players in disaster responses but their knowledge levels of disaster medicine are not readily available. This study aimed to evaluate knowledge levels and training needs of disaster medicine among potential disaster responders and presented a necessity to popularize disaster medicine education. METHODS: A self-reporting questionnaire survey on knowledge level and training needs of disaster medicine was conducted in Shanghai, China, in 2012. A total of randomly selected 547 health professionals, 456 medical students, and 1,526 local residents provided intact information. The total response rate was 93.7%. RESULTS: Overall, 1.3% of these participants have received systematic disaster medicine training. News media (87.1%) was the most common channel to acquire disaster medicine knowledge. Although health professionals were more knowledgeable than community residents, their knowledge structure of disaster medicine was not intact. Medical teachers were more knowledgeable than medical practitioners and health administrators (p = 0.002). Clinicians performed better than public health physicians (p<0.001), whereas public health students performed better than clinical medical students (p<0.001). In community residents, education background significantly affected the knowledge level on disaster medicine (p<0.001). Training needs of disaster medicine were generally high among the surveyed. ‘Lecture’ and ‘practical training’ were preferred teaching methods. The selected key and interested contents on disaster medicine training were similar between health professionals and medical students, while the priorities chosen by local residents were quite different from health professionals and medical students (p<0.001). CONCLUSIONS: Traditional clinical-oriented medical education might lead to a huge gap between the knowledge level on disaster medicine and the current needs of disaster preparedness. Continuing medical education and public education plans on disaster medicine via media should be practice-oriented, and selectively applied to different populations and take the knowledge levels and training needs into consideration.",2013 Jun 24,"['Su, Tong', 'Han, Xue', 'Chen, Fei', 'Du, Yan', 'Zhang, Hongwei', 'Yin, Jianhua', 'Tan, Xiaojie', 'Chang, Wenjun', 'Ding, Yibo', 'Han, Yifang', 'Cao, Guangwen']",PLoS One,,,True
ddd0fb0cae99bad6466775c11b4d5a0c30be9219,PMC,Different Types of Door-Opening Motions as Contributing Factors to Containment Failures in Hospital Isolation Rooms,http://dx.doi.org/10.1371/journal.pone.0066663,PMC3691190,23826109,CC BY,"Hospital isolation rooms are vital for the containment (when under negative pressure) of patients with, or the protection (when under positive pressure) of patients, from airborne infectious agents. Such facilities were essential for the management of highly contagious patients during the 2003 severe acute respiratory syndrome (SARS) outbreaks and the more recent 2009 A/H1N1 influenza pandemic. Many different types of door designs are used in the construction of such isolation rooms, which may be related to the space available and affordability. Using colored food dye as a tracer, the qualitative effects of door-opening motions on the dissemination of potentially contaminated air into and out of a single isolation room were visualized and filmed using Reynolds-number-equivalent, small-scale, water-tank models fitted with programmable door-opening and moving human figure motions. Careful scaling considerations involved in the design and construction of these water-tank models enabled these results to be accurately extrapolated to the full-scale situation. Four simple types of door design were tested: variable speed single and double, sliding and hinged doors, in combination with the moving human figure. The resulting video footage was edited, synchronized and presented in a series of split-screen formats. From these experiments, it is clear that double-hinged doors pose the greatest risk of leakage into or out of the room, followed by (in order of decreasing risk) single-hinged, double-sliding and single-sliding doors. The relative effect of the moving human figure on spreading any potential contamination was greatest with the sliding doors, as the bulk airflows induced were large relative to those resulting from these door-opening motions. However, with the hinged doors, the airflows induced by these door-opening motions were significantly greater. Further experiments involving a simulated ventilated environment are required, but from these findings alone, it appears that sliding-doors are far more effective for hospital isolation room containment.",2013 Jun 24,"['Tang, Julian W.', 'Nicolle, Andre', 'Pantelic, Jovan', 'Klettner, Christian A.', 'Su, Ruikun', 'Kalliomaki, Petri', 'Saarinen, Pekka', 'Koskela, Hannu', 'Reijula, Kari', 'Mustakallio, Panu', 'Cheong, David K. W.', 'Sekhar, Chandra', 'Tham, Kwok Wai']",PLoS One,,,True
7f3e18a9a954832a2335fa3c26c42f127a79855c,PMC,MEK/ERK Dependent Activation of STAT1 Mediates Dasatinib-Induced Differentiation of Acute Myeloid Leukemia,http://dx.doi.org/10.1371/journal.pone.0066915,PMC3692534,23825585,CC BY,"Dasatinib (BMS-354825) is a FDA-approved multitargeted kinase inhibitor of BCR/ABL and Src kinases. It is now used in the treatment of chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapies, including imatinib. Here we report a novel effect of dasatinib on inducing the differentiation of acute myeloid leukemia (AML) cells through MEK/ERK-dependent activation of signal transducer and activator of transcription 1 (STAT1). We found that dasatinib could induce the differentiation of AML cells as demonstrated by the expression of differentiation marker CD11b, G0/G1 phase arrest and decreased ratio of nucleus to cytoplasm. Of note, dasatinib induced robust phosphorylation of STAT1 both at Tyr701 and Ser727 as well as the redistribution of STAT1 from the cytoplasm to the nucleus, thus leading to the transcription of STAT1-targeted genes. Knocking down STAT1 expression by shRNA significantly attenuated dasatinib-induced differentiation, indicating an important role of STAT1 in myeloid maturation. We further found that dasatinib-induced activation of STAT1 was regulated by the MEK/ERK kinases. The phosporylation of MEK and ERK occurred rapidly upon dasatinib treatment and increased progressively as differentiation was induced. MEK inhibitors PD98059 and U0216 not only inhibited the phosphorylation of STAT1, but also abrogated dasatinib-induced myeloid differentiation, suggesting that MEK/ERK dependent phosphorylation of STAT1 might be indispensable for the differentiating effect of dasatinib in AML cells. Taken together, our study suggests that STAT1 is an important mediator in dasatinib-induced differentiation of AML cells, whose activation requires the activation of MEK/ERK cascades.",2013 Jun 25,"['Fang, Yanfen', 'Zhong, Like', 'Lin, Meihua', 'Zhou, Xinglu', 'Jing, Hui', 'Ying, Meidan', 'Luo, Peihua', 'Yang, Bo', 'He, Qiaojun']",PLoS One,,,True
3f7b6af5cd76098945fd076e4fa43a541fb7a5a0,PMC,"Availability, consistency and evidence-base of policies and guidelines on the use of mask and respirator to protect hospital health care workers: a global analysis",http://dx.doi.org/10.1186/1756-0500-6-216,PMC3693993,23725338,CC BY,"BACKGROUND: Currently there is an ongoing debate and limited evidence on the use of masks and respirators for the prevention of respiratory infections in health care workers (HCWs). This study aimed to examine available policies and guidelines around the use of masks and respirators in HCWs and to describe areas of consistency between guidelines, as well as gaps in the recommendations, with reference to the WHO and the CDC guidelines. METHODS: Policies and guidelines related to mask and respirator use for the prevention of influenza, SARS and TB were examined. Guidelines from the World Health Organization (WHO), the Center for Disease Control and Prevention (CDC), three high-income countries and six low/middle-income countries were selected. RESULTS: Uniform recommendations are made by the WHO and the CDC in regards to protecting HCWs against seasonal influenza (a mask for low risk situations and a respirator for high risk situations) and TB (use of a respirator). However, for pandemic influenza and SARS, the WHO recommends mask use in low risk and respirators in high risk situations, whereas, the CDC recommends respirators in both low and high risk situations. Amongst the nine countries reviewed, there are variations in the recommendations for all three diseases. While, some countries align with the WHO recommendations, others align with those made by the CDC. The choice of respirator and the level of filtering ability vary amongst the guidelines and the different diseases. Lastly, none of the policies discuss reuse, extended use or the use of cloth masks. CONCLUSION: Currently, there are significant variations in the policies and recommendations around mask and respirator use for protection against influenza, SARS and TB. These differences may reflect the scarcity of level-one evidence available to inform policy development. The lack of any guidelines on the use of cloth masks, despite widespread use in many low and middle-income countries, remains a policy gap. Health organizations and countries should jointly evaluate the available evidence, prioritize research to inform evidence gaps, and develop consistent policy on masks and respirator use in the health care setting.",2013 May 31,"['Chughtai, Abrar Ahmad', 'Seale, Holly', 'MacIntyre, Chandini Raina']",BMC Res Notes,,,True
1f7d12535c961aa81e3719db27546b741674c1aa,PMC,Infectious Bronchitis Virus as a Vector for the Expression of Heterologous Genes,http://dx.doi.org/10.1371/journal.pone.0067875,PMC3694013,23840781,CC BY,"The avian coronavirus infectious bronchitis virus (IBV) is the causative agent of the respiratory disease infectious bronchitis of domestic fowl, and is controlled by routine vaccination. To explore the potential use of IBV as a vaccine vector a reverse genetics system was utilised to generate infectious recombinant IBVs (rIBVs) expressing the reporter genes enhanced green fluorescent protein (eGFP) or humanised Renilla luciferase (hRluc). Infectious rIBVs were obtained following the replacement of Gene 5 or the intergenic region (IR) with eGFP or hRluc, or the replacement of ORFs 3a and 3b with hRluc. The replacement of Gene 5 with an IBV codon-optimised version of the hRluc gene also resulted in successful rescue of infectious rIBV. Reporter gene expression was confirmed by fluorescence microscopy, or luciferase activity assays, for all successfully rescued rIBVs following infection of primary chick kidney (CK) cells. The genetic stability of rIBVs was analysed by serial passage on CK cells. Recombinant IBV stability varied depending on the genome region being replaced, with the reporter genes maintained up to at least passage 8 (P8) following replacement of Gene 5, P7 for replacement of the IR and P5 for replacement of ORFs 3a and 3b. Codon-optimisation of the hRluc gene, when replacing Gene 5, resulted in an increase in genome stability, with hRluc expression stable up to P10 compared to P8 for standard hRluc. Repeated passaging of rIBVs expressing hRluc at an MOI of 0.01 demonstrated an increase in stability, with hRluc expression stable up to at least P12 following the replacement of Gene 5. This study has demonstrated that heterologous genes can be incorporated into, and expressed from a range of IBV genome locations and that replacement of accessory Gene 5 offers a promising target for realising the potential of IBV as a vaccine vector for other avian pathogens.",2013 Jun 26,"['Bentley, Kirsten', 'Armesto, Maria', 'Britton, Paul']",PLoS One,,,True
4156b347411e4071b10550a6acc2725c5e82df99,PMC,Neutrophils Turn Plasma Proteins into Weapons against HIV-1,http://dx.doi.org/10.1371/journal.pone.0066073,PMC3694086,23840401,CC BY,"As a consequence of innate immune activation granulocytes and macrophages produce hypochlorite/hypochlorous acid (HOCl) via secretion of myeloperoxidase (MPO) to the outside of the cells, where HOCl immediately reacts with proteins. Most proteins that become altered by this system do not belong to the invading microorganism but to the host. While there is no doubt that the myeloperoxidase system is capable of directly inactivating HIV-1, we hypothesized that it may have an additional indirect mode of action. We show in this article that HOCl is able to chemically alter proteins and thus turn them into Idea-Ps (Idea-P = immune defence-altered protein), potent amyloid-like and SH-groups capturing antiviral weapons against HIV-1. HOCl-altered plasma proteins (Idea-PP) have the capacity to bind efficiently and with high affinity to the HIV-1 envelope protein gp120, and to its receptor CD4 as well as to the protein disulfide isomerase (PDI). Idea-PP was able to inhibit viral infection and replication in a cell culture system as shown by reduced number of infected cells and of syncytia, resulting in reduction of viral capsid protein p24 in the culture supernatant. The unmodified plasma protein fraction had no effect. HOCl-altered isolated proteins antithrombin III and human serum albumin, taken as representative examples of the whole pool of plasma proteins, were both able to exert the same activity of binding to gp120 and inhibition of viral proliferation. These data offer an opportunity to improve the understanding of the intricacies of host-pathogen interactions and allow the generation of the following hypothetical scheme: natural immune defense mechanisms generate by posttranslational modification of plasma proteins a potent virucidal weapon that immobilizes the virus as well as inhibits viral fusion and thus entry into the host cells. Furthermore simulation of this mechanism in vitro might provide an interesting new therapeutic approach against microorganisms.",2013 Jun 26,"['Speth, Cornelia', 'Brodde, Martin F.', 'Hagleitner, Magdalena', 'Rambach, Günter', 'Van Aken, Hugo', 'Dierich, Manfred', 'Kehrel, Beate E.']",PLoS One,,,True
91ac78d2a3c677d322fc8b14bc23e6b4244b5bdc,PMC,Comparison of Heterologous Prime-Boost Strategies against Human Immunodeficiency Virus Type 1 Gag Using Negative Stranded RNA Viruses,http://dx.doi.org/10.1371/journal.pone.0067123,PMC3694142,23840600,CC BY,"This study analyzed a heterologous prime-boost vaccine approach against HIV-1 using three different antigenically unrelated negative-stranded viruses (NSV) expressing HIV-1 Gag as vaccine vectors: rabies virus (RABV), vesicular stomatitis virus (VSV) and Newcastle disease virus (NDV). We hypothesized that this approach would result in more robust cellular immune responses than those achieved with the use of any of the vaccines alone in a homologous prime-boost regimen. To this end, we primed BALB/c mice with each of the NSV-based vectors. Primed mice were rested for thirty-five days after which we administered a second immunization with the same or heterologous NSV-Gag viruses. The magnitude and quality of the Gag-specific CD8(+) T cells in response to these vectors post boost were measured. In addition, we performed challenge experiments using vaccinia virus expressing HIV-1 Gag (VV-Gag) thirty-three days after the boost inoculation. Our results showed that the choice of the vaccine used for priming was important for the detected Gag-specific CD8(+) T cell recall responses post boost and that NDV-Gag appeared to result in a more robust recall of CD8(+) T cell responses independent of the prime vaccine used. However, the different prime-boost strategies were not distinct for the parameters studied in the challenge experiments using VV-Gag but did indicate some benefits compared to single immunizations. Taken together, our data show that NSV vectors can individually stimulate HIV-Gag specific CD8(+) T cells that are effectively recalled by other NSV vectors in a heterologous prime-boost approach. These results provide evidence that RABV, VSV and NDV can be used in combination to develop vaccines needing prime-boost regimens to stimulate effective immune responses.",2013 Jun 26,"['Lawrence, Tessa M.', 'Wanjalla, Celestine N.', 'Gomme, Emily A.', 'Wirblich, Christoph', 'Gatt, Anthony', 'Carnero, Elena', 'García-Sastre, Adolfo', 'Lyles, Douglas S.', 'McGettigan, James P.', 'Schnell, Matthias J.']",PLoS One,,,True
7c73591901ddde49d3ebba7410f2e2da1ceb6707,PMC,Towards Systematic Discovery of Signaling Networks in Budding Yeast Filamentous Growth Stress Response Using Interventional Phosphorylation Data,http://dx.doi.org/10.1371/journal.pcbi.1003077,PMC3694812,23825934,CC BY,"Reversible phosphorylation is one of the major mechanisms of signal transduction, and signaling networks are critical regulators of cell growth and development. However, few of these networks have been delineated completely. Towards this end, quantitative phosphoproteomics is emerging as a useful tool enabling large-scale determination of relative phosphorylation levels. However, phosphoproteomics differs from classical proteomics by a more extensive sampling limitation due to the limited number of detectable sites per protein. Here, we propose a comprehensive quantitative analysis pipeline customized for phosphoproteome data from interventional experiments for identifying key proteins in specific pathways, discovering the protein-protein interactions and inferring the signaling network. We also made an effort to partially compensate for the missing value problem, a chronic issue for proteomics studies. The dataset used for this study was generated using SILAC (Stable Isotope Labeling with Amino acids in Cell culture) technique with interventional experiments (kinase-dead mutations). The major components of the pipeline include phosphopeptide meta-analysis, correlation network analysis and causal relationship discovery. We have successfully applied our pipeline to interventional experiments identifying phosphorylation events underlying the transition to a filamentous growth form in Saccharomyces cerevisiae. We identified 5 high-confidence proteins from meta-analysis, and 19 hub proteins from correlation analysis (Pbi2p and Hsp42p were identified by both analyses). All these proteins are involved in stress responses. Nine of them have direct or indirect evidence of involvement in filamentous growth. In addition, we tested four of our predicted proteins, Nth1p, Pbi2p, Pdr12p and Rcn2p, by interventional phenotypic experiments and all of them present differential invasive growth, providing prospective validation of our approach. This comprehensive pipeline presents a systematic way for discovering signaling networks using interventional phosphoproteome data and can suggest candidate proteins for further investigation. We anticipate the methodology to be applicable as well to other interventional studies via different experimental platforms.",2013 Jun 27,"['Zhang, Yan', 'Kweon, Hye Kyong', 'Shively, Christian', 'Kumar, Anuj', 'Andrews, Philip C.']",PLoS Comput Biol,,,True
e0531f9c84005ac77b1bdb3075c486e6ac116760,PMC,Towards Systematic Discovery of Signaling Networks in Budding Yeast Filamentous Growth Stress Response Using Interventional Phosphorylation Data,http://dx.doi.org/10.1371/journal.pcbi.1003077,PMC3694812,23825934,CC BY,"Reversible phosphorylation is one of the major mechanisms of signal transduction, and signaling networks are critical regulators of cell growth and development. However, few of these networks have been delineated completely. Towards this end, quantitative phosphoproteomics is emerging as a useful tool enabling large-scale determination of relative phosphorylation levels. However, phosphoproteomics differs from classical proteomics by a more extensive sampling limitation due to the limited number of detectable sites per protein. Here, we propose a comprehensive quantitative analysis pipeline customized for phosphoproteome data from interventional experiments for identifying key proteins in specific pathways, discovering the protein-protein interactions and inferring the signaling network. We also made an effort to partially compensate for the missing value problem, a chronic issue for proteomics studies. The dataset used for this study was generated using SILAC (Stable Isotope Labeling with Amino acids in Cell culture) technique with interventional experiments (kinase-dead mutations). The major components of the pipeline include phosphopeptide meta-analysis, correlation network analysis and causal relationship discovery. We have successfully applied our pipeline to interventional experiments identifying phosphorylation events underlying the transition to a filamentous growth form in Saccharomyces cerevisiae. We identified 5 high-confidence proteins from meta-analysis, and 19 hub proteins from correlation analysis (Pbi2p and Hsp42p were identified by both analyses). All these proteins are involved in stress responses. Nine of them have direct or indirect evidence of involvement in filamentous growth. In addition, we tested four of our predicted proteins, Nth1p, Pbi2p, Pdr12p and Rcn2p, by interventional phenotypic experiments and all of them present differential invasive growth, providing prospective validation of our approach. This comprehensive pipeline presents a systematic way for discovering signaling networks using interventional phosphoproteome data and can suggest candidate proteins for further investigation. We anticipate the methodology to be applicable as well to other interventional studies via different experimental platforms.",2013 Jun 27,"['Zhang, Yan', 'Kweon, Hye Kyong', 'Shively, Christian', 'Kumar, Anuj', 'Andrews, Philip C.']",PLoS Comput Biol,,,True
5908982f4dbbfde0faabcfadc0988b8a19223411,PMC,Evasion of Antiviral Innate Immunity by Theiler's Virus L* Protein through Direct Inhibition of RNase L,http://dx.doi.org/10.1371/journal.ppat.1003474,PMC3694852,23825954,CC BY,"Theiler's virus is a neurotropic picornavirus responsible for chronic infections of the central nervous system. The establishment of a persistent infection and the subsequent demyelinating disease triggered by the virus depend on the expression of L*, a viral accessory protein encoded by an alternative open reading frame of the virus. We discovered that L* potently inhibits the interferon-inducible OAS/RNase L pathway. The antagonism of RNase L by L* was particularly prominent in macrophages where baseline oligoadenylate synthetase (OAS) and RNase L expression levels are elevated, but was detectable in fibroblasts after IFN pretreatment. L* mutations significantly affected Theiler's virus replication in primary macrophages derived from wild-type but not from RNase L-deficient mice. L* counteracted the OAS/RNase L pathway through direct interaction with the ankyrin domain of RNase L, resulting in the inhibition of this enzyme. Interestingly, RNase L inhibition was species-specific as Theiler's virus L* protein blocked murine RNase L but not human RNase L or RNase L of other mammals or birds. Direct RNase L inhibition by L* and species specificity were confirmed in an in vitro assay performed with purified proteins. These results demonstrate a novel viral mechanism to elude the antiviral OAS/RNase L pathway. By targeting the effector enzyme of this antiviral pathway, L* potently inhibits RNase L, underscoring the importance of this enzyme in innate immunity against Theiler's virus.",2013 Jun 27,"['Sorgeloos, Frédéric', 'Jha, Babal Kant', 'Silverman, Robert H.', 'Michiels, Thomas']",PLoS Pathog,,,True
3154395f4f53dd3c358e5ba72e394f9334430cef,PMC,A Simulation Optimization Approach to Epidemic Forecasting,http://dx.doi.org/10.1371/journal.pone.0067164,PMC3694918,23826222,CC BY,"Reliable forecasts of influenza can aid in the control of both seasonal and pandemic outbreaks. We introduce a simulation optimization (SIMOP) approach for forecasting the influenza epidemic curve. This study represents the final step of a project aimed at using a combination of simulation, classification, statistical and optimization techniques to forecast the epidemic curve and infer underlying model parameters during an influenza outbreak. The SIMOP procedure combines an individual-based model and the Nelder-Mead simplex optimization method. The method is used to forecast epidemics simulated over synthetic social networks representing Montgomery County in Virginia, Miami, Seattle and surrounding metropolitan regions. The results are presented for the first four weeks. Depending on the synthetic network, the peak time could be predicted within a 95% CI as early as seven weeks before the actual peak. The peak infected and total infected were also accurately forecasted for Montgomery County in Virginia within the forecasting period. Forecasting of the epidemic curve for both seasonal and pandemic influenza outbreaks is a complex problem, however this is a preliminary step and the results suggest that more can be achieved in this area.",2013 Jun 27,"['Nsoesie, Elaine O.', 'Beckman, Richard J.', 'Shashaani, Sara', 'Nagaraj, Kalyani S.', 'Marathe, Madhav V.']",PLoS One,,,True
94f391ebd1b25ac7fb8159d7b24b7414c582a630,PMC,A Simulation Optimization Approach to Epidemic Forecasting,http://dx.doi.org/10.1371/journal.pone.0067164,PMC3694918,23826222,CC BY,"Reliable forecasts of influenza can aid in the control of both seasonal and pandemic outbreaks. We introduce a simulation optimization (SIMOP) approach for forecasting the influenza epidemic curve. This study represents the final step of a project aimed at using a combination of simulation, classification, statistical and optimization techniques to forecast the epidemic curve and infer underlying model parameters during an influenza outbreak. The SIMOP procedure combines an individual-based model and the Nelder-Mead simplex optimization method. The method is used to forecast epidemics simulated over synthetic social networks representing Montgomery County in Virginia, Miami, Seattle and surrounding metropolitan regions. The results are presented for the first four weeks. Depending on the synthetic network, the peak time could be predicted within a 95% CI as early as seven weeks before the actual peak. The peak infected and total infected were also accurately forecasted for Montgomery County in Virginia within the forecasting period. Forecasting of the epidemic curve for both seasonal and pandemic influenza outbreaks is a complex problem, however this is a preliminary step and the results suggest that more can be achieved in this area.",2013 Jun 27,"['Nsoesie, Elaine O.', 'Beckman, Richard J.', 'Shashaani, Sara', 'Nagaraj, Kalyani S.', 'Marathe, Madhav V.']",PLoS One,,,True
d7b6ba6c543bcfd967c19fc3663abee090ed3a25,PMC,Duration of Maternal Antibodies against Canine Distemper Virus and Hendra Virus in Pteropid Bats,http://dx.doi.org/10.1371/journal.pone.0067584,PMC3695084,23826322,CC BY,"Old World frugivorous bats have been identified as natural hosts for emerging zoonotic viruses of significant public health concern, including henipaviruses (Nipah and Hendra virus), Ebola virus, and Marburg virus. Epidemiological studies of these viruses in bats often utilize serology to describe viral dynamics, with particular attention paid to juveniles, whose birth increases the overall susceptibility of the population to a viral outbreak once maternal immunity wanes. However, little is understood about bat immunology, including the duration of maternal antibodies in neonates. Understanding duration of maternally derived immunity is critical for characterizing viral dynamics in bat populations, which may help assess the risk of spillover to humans. We conducted two separate studies of pregnant Pteropus bat species and their offspring to measure the half-life and duration of antibodies to 1) canine distemper virus antigen in vaccinated captive Pteropus hypomelanus; and 2) Hendra virus in wild-caught, naturally infected Pteropus alecto. Both of these pteropid bat species are known reservoirs for henipaviruses. We found that in both species, antibodies were transferred from dam to pup. In P. hypomelanus pups, titers against CDV waned over a mean period of 228.6 days (95% CI: 185.4–271.8) and had a mean terminal phase half-life of 96.0 days (CI 95%: 30.7–299.7). In P. alecto pups, antibodies waned over 255.13 days (95% CI: 221.0–289.3) and had a mean terminal phase half-life of 52.24 days (CI 95%: 33.76–80.83). Each species showed a duration of transferred maternal immunity of between 7.5 and 8.5 months, which was longer than has been previously estimated. These data will allow for more accurate interpretation of age-related Henipavirus serological data collected from wild pteropid bats.",2013 Jun 27,"['Epstein, Jonathan H.', 'Baker, Michelle L.', 'Zambrana-Torrelio, Carlos', 'Middleton, Deborah', 'Barr, Jennifer A.', 'DuBovi, Edward', 'Boyd, Victoria', 'Pope, Brian', 'Todd, Shawn', 'Crameri, Gary', 'Walsh, Allyson', 'Pelican, Katey', 'Fielder, Mark D.', 'Davies, Angela J.', 'Wang, Lin-Fa', 'Daszak, Peter']",PLoS One,,,True
3331e1bb231ae4227e4b6e8e98412b17468747a1,PMC,Protein co-expression network analysis (ProCoNA),http://dx.doi.org/10.1186/2043-9113-3-11,PMC3695838,23724967,CC BY,"BACKGROUND: Biological networks are important for elucidating disease etiology due to their ability to model complex high dimensional data and biological systems. Proteomics provides a critical data source for such models, but currently lacks robust de novo methods for network construction, which could bring important insights in systems biology. RESULTS: We have evaluated the construction of network models using methods derived from weighted gene co-expression network analysis (WGCNA). We show that approximately scale-free peptide networks, composed of statistically significant modules, are feasible and biologically meaningful using two mouse lung experiments and one human plasma experiment. Within each network, peptides derived from the same protein are shown to have a statistically higher topological overlap and concordance in abundance, which is potentially important for inferring protein abundance. The module representatives, called eigenpeptides, correlate significantly with biological phenotypes. Furthermore, within modules, we find significant enrichment for biological function and known interactions (gene ontology and protein-protein interactions). CONCLUSIONS: Biological networks are important tools in the analysis of complex systems. In this paper we evaluate the application of weighted co-expression network analysis to quantitative proteomics data. Protein co-expression networks allow novel approaches for biological interpretation, quality control, inference of protein abundance, a framework for potentially resolving degenerate peptide-protein mappings, and a biomarker signature discovery.",2013 Jun 1,"['Gibbs, David L', 'Baratt, Arie', 'Baric, Ralph S', 'Kawaoka, Yoshihiro', 'Smith, Richard D', 'Orwoll, Eric S', 'Katze, Michael G', 'McWeeney, Shannon K']",J Clin Bioinforma,,,True
914d646494f09cbb34bbe5da9dfea4c93ad35bb9,PMC,Rhabdomyolysis Associated with Parainfluenza Virus,http://dx.doi.org/10.1155/2013/650965,PMC3697188,23840985,CC BY,"Influenza virus is the most frequently reported viral cause of rhabdomyolysis. A 7-year-old child is presented with rhabdomyolysis associated with parainfluenza type 2 virus. Nine cases of rhabdomyolysis associated with parainfluenza virus have been reported. Complications may include electrolyte disturbances, acute renal failure, and compartment syndrome.",2013 Jun 13,"['Douvoyiannis, Miltiadis', 'Kielbasa, Johanna M.', 'Chandrasekharan, Gopal M.', 'Holmes, Cynthia L.', 'Gomez, Michael R.']",Case Rep Infect Dis,,,True
3a744992aeec8bfdcfc35035187791f3c8613f41,PMC,Scorpion Peptides: Potential Use for New Drug Development,http://dx.doi.org/10.1155/2013/958797,PMC3697785,23843786,CC BY,"Several peptides contained in scorpion fluids showed diverse array of biological activities with high specificities to their targeted sites. Many investigations outlined their potent effects against microbes and showed their potential to modulate various biological mechanisms that are involved in immune, nervous, cardiovascular, and neoplastic diseases. Because of their important structural and functional diversity, it is projected that scorpion-derived peptides could be used to develop new specific drugs. This review summarizes relevant findings improving their use as valuable tools for new drugs development.",2013 Jun 15,"['Hmed, BenNasr', 'Serria, Hammami Turky', 'Mounir, Zeghal Khaled']",J Toxicol,,,True
e5407e15d4e044411687f36176bc9d27bb6a3fd4,PMC,TRAF molecules in cell signaling and in human diseases,http://dx.doi.org/10.1186/1750-2187-8-7,PMC3697994,23758787,CC BY,"The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of intracellular proteins were originally identified as signaling adaptors that bind directly to the cytoplasmic regions of receptors of the TNF-R superfamily. The past decade has witnessed rapid expansion of receptor families identified to employ TRAFs for signaling. These include Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), T cell receptor, IL-1 receptor family, IL-17 receptors, IFN receptors and TGFβ receptors. In addition to their role as adaptor proteins, most TRAFs also act as E3 ubiquitin ligases to activate downstream signaling events. TRAF-dependent signaling pathways typically lead to the activation of nuclear factor-κBs (NF-κBs), mitogen-activated protein kinases (MAPKs), or interferon-regulatory factors (IRFs). Compelling evidence obtained from germ-line and cell-specific TRAF-deficient mice demonstrates that each TRAF plays indispensable and non-redundant physiological roles, regulating innate and adaptive immunity, embryonic development, tissue homeostasis, stress response, and bone metabolism. Notably, mounting evidence implicates TRAFs in the pathogenesis of human diseases such as cancers and autoimmune diseases, which has sparked new appreciation and interest in TRAF research. This review presents an overview of the current knowledge of TRAFs, with an emphasis on recent findings concerning TRAF molecules in signaling and in human diseases.",2013 Jun 13,"Xie, Ping",J Mol Signal,,,True
0e6f08bde4abd9fb12aa599c325e381692c83125,PMC,"Comparison among nasopharyngeal swab, nasal wash, and oropharyngeal swab for respiratory virus detection in adults with acute pharyngitis",http://dx.doi.org/10.1186/1471-2334-13-281,PMC3698019,23786598,CC BY,"BACKGROUND: Acute pharyngitis is frequently seen in primary care. Acute viral pharyngitis may be easily misdiagnosed as acute bacterial pharyngitis. Laboratory-confirmed diagnosis of respiratory viruses is recommended. The purpose of this study was to compare the sensitivities among oropharyngeal swab (OPS), nasopharyngeal swab (NPS), and nasal wash (NW) in adults with acute pharyngitis. METHODS: OPS, NPS, and NW were obtained from each participant with acute pharyngitis. The specimens were tested for 15 respiratory viruses by TaqMan real-time polymerase chain reaction. A sample was considered to be a true positive if any of the specimens was positive. The sensitivities among samples were compared by chi-square test or Fisher’s exact test, as appropriate. RESULTS: One hundred three triple samples collected consecutively by OPS, NPS, and NW were obtained. In 73 patients, one or more viruses were detected by any of the three methods. Among all viruses, the sensitivity of NPS was significantly higher than that of NW (74% vs. 49%, respectively; p < 0.01) and OPS (74% vs. 49%, respectively; p < 0.01). CONCLUSIONS: Flocked NPS collection may be the most effective alternative to NW and OPS for detection of respiratory viruses in adults with acute pharyngitis using TaqMan real-time polymerase chain reaction.",2013 Jun 20,"['Li, Li', 'Chen, Qiao-Yan', 'Li, Yun-Ying', 'Wang, Yan-Fang', 'Yang, Zi-Feng', 'Zhong, Nan-Shan']",BMC Infect Dis,,,True
d4771e9bbc00e3937638507817289579abc270bc,PMC,Effect of black tea extract on herpes simplex virus-1 infection of cultured cells,http://dx.doi.org/10.1186/1472-6882-13-139,PMC3698045,23777309,CC BY,"BACKGROUND: The purpose of this investigation was to determine if black tea extract (BTE), consisting primarily of flavanol compounds called theaflavins, could inhibit herpes simplex virus type-1 (HSV-1) infection in cultured A549 (human epithelial) and Vero cells. METHODS: The effect of BTE both on A549 and Vero cultured cells and on HSV-1 was assessed by using phase contrast and fluorescent microscopy, and cell viability and proliferation assays. After establishing the maximum non-cytotoxic concentration of BTE, A549 and Vero cells and HSV-1 virions were treated with varying concentrations of BTE, respectively. A549 and Vero cells were infected with HSV-1 with green fluorescent protein (GFP) insert at the UL46 gene. The effect of infectivity was determined by viral DNA extraction followed by PCR, plaque assays, adsorption assays, and electrophoresis of PCR products. RESULTS: BTE was not cytotoxic to A549 and Vero cells, as confirmed by cell viability and proliferation assays, in which BTE treated groups paralleled the positive control group. For both cell lines, plaque assays and fluorescent microscopy indicated an inverse relationship between BTE concentration (from 0.14 μM – 1.4 mM) and HSV-1 infectivity. Specifically, PCR and electrophoresis showed a reduction in the viral genome following treatment with BTE. In addition, there was a noticeable decrease in the amount of viral plaques for BTE treated samples in the adsorption assays. CONCLUSIONS: BTE consisting primarily of theaflavins is not cytotoxic and can reduce or block the production of infectious HSV-1 virions in cultured A549 and Vero cells, thus inhibiting the infectivity of the virus by interfering in the attachment, penetration and viral DNA replication of HSV-1 particles. These findings indicate that BTE enriched with theaflavins has the potential to be developed as a safe, therapeutic antiviral agent to prevent the spread of HSV-1.",2013 Jun 18,"['Cantatore, Anthony', 'Randall, Sade D', 'Traum, Daniel', 'Adams, Sandra D']",BMC Complement Altern Med,,,True
f2659bd84b8347a97b54698fbc1dea43ef10a85e,PMC,Hepatic Deficiency of COP9 Signalosome Subunit 8 Induces Ubiquitin-Proteasome System Impairment and Bim-Mediated Apoptosis in Murine Livers,http://dx.doi.org/10.1371/journal.pone.0067793,PMC3698095,23840878,CC BY,"The COP9 signalosome (CSN), an evolutionally highly conserved protein complex composed of 8 unique subunits (CSN1 through CSN8) in higher eukaryotes, is purported to modulate protein degradation mediated by the ubiquitin-proteasome system (UPS) but this has not been demonstrated in a critical mitotic parenchymal organ of vertebrates. Hepatocyte-specific knockout of the Cops8 gene (HS-Csn8KO) was shown to cause massive hepatocyte apoptosis and liver malfunction but the underlying mechanism remains unclear. Here, we report that Csn8/CSN exerts profound impacts on hepatic UPS function and is critical to the stability of the pro-apoptotic protein Bim. Significant decreases in CIS (cytokine-inducible Src homology 2 domain-containing protein), a Bim receptor of a cullin2-based ubiquitin ligase, were found to co-exist with a marked increase of Bim proteins. Csn8 deficiency also significantly decreased 19S proteasome subunit Rpt5 and markedly increased high molecular weight neddylated and ubiquitinated proteins. The use of a surrogate UPS substrate further reveals severe impairment of UPS-mediated proteolysis in HS-Csn8KO livers. Inclusion body-like materials were accumulated in Csn8 deficient hepatocytes. In addition to Bim, massive hepatocyte apoptosis in HS-Csn8KO livers is also associated with elevated expression of other members of the Bcl2 family, including pro-apoptotic Bax as well as anti-apoptotic Bcl2 and Bcl-XL. Increased interaction between Bcl2 and Bim, but not between Bcl2 and Bax, was detected. Hence, it is concluded that hepatic CSN8 deficiency impairs the UPS in the liver and the resultant Bim upregulation likely plays an important role in triggering hepatocyte apoptosis via sequestering Bcl2 away from Bax.",2013 Jul 1,"['Lei, Daoxiong', 'Li, Faqian', 'Su, Huabo', 'Liu, Jinbao', 'Wei, Ning', 'Wang, Xuejun']",PLoS One,,,True
f1541ead6bf6988b4d08b12873806a89a4b7ff1b,PMC,In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus,http://dx.doi.org/10.1371/journal.pone.0068053,PMC3699466,23844154,CC BY,"BACKGROUND: Staphylococcus aureus can cause severe infections, including bacteremia and sepsis. The spread of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for novel treatment options. Sodium new houttuyfonate (SNH) is an analogue of houttuynin, the main antibacterial ingredient of Houttuynia cordata Thunb. The aim of this study was to evaluate in vitro activity of SNH and its potential for synergy with antibiotics against hospital-associated MRSA. METHODOLOGY: A total of 103 MRSA clinical isolates recovered in two hospitals in Beijing were evaluated for susceptibility to SNH, oxacillin, cephalothin, meropenem, vancomycin, levofloxacin, minocycline, netilmicin, and trimethoprim/sulfamethoxazole by broth microdilution. Ten isolates were evaluated for potential for synergy between SNH and the antibiotics above by checkerboard assay. Time-kill analysis was performed in three isolates to characterize the kill kinetics of SNH alone and in combination with the antibiotics that engendered synergy in checkerboard assays. Besides, two reference strains were included in all assays. PRINCIPAL FINDINGS: SNH inhibited all test strains with minimum inhibitory concentrations (MICs) ranging from 16 to 64 µg/mL in susceptibility tests, and displayed inhibition to bacterial growth in concentration-dependent manner in time-kill analysis. In synergy studies, the combinations of SNH-oxacillin, SNH-cephalothin, SNH-meropenem and SNH-netilmicin showed synergistic effects against 12 MRSA strains with median fractional inhibitory concentration (FIC) indices of 0.38, 0.38, 0.25 and 0.38 in checkerboard assays. In time-kill analysis, SNH at 1/2 MIC in combination with oxacillin at 1/128 to 1/64 MIC or netilmicin at 1/8 to 1/2 MIC decreased the viable colonies by ≥2log(10) CFU/mL. CONCLUSIONS/SIGNIFICANCE: SNH demonstrated in vitro antibacterial activity against 103 hospital-associated MRSA isolates. Combinations of sub-MIC levels of SNH and oxacillin or netilmicin significantly improved the in vitro antibacterial activity against MRSA compared with either drug alone. The SNH-based combinations showed promise in combating MRSA.",2013 Jul 2,"['Lu, Xi', 'Yang, Xinyi', 'Li, Xue', 'Lu, Yun', 'Ren, Zhitao', 'Zhao, Longyin', 'Hu, Xinxin', 'Jiang, Jiandong', 'You, Xuefu']",PLoS One,,,True
5cbecfc7afe8168effb452c060f809c55ccbf880,PMC,In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus,http://dx.doi.org/10.1371/journal.pone.0068053,PMC3699466,23844154,CC BY,"BACKGROUND: Staphylococcus aureus can cause severe infections, including bacteremia and sepsis. The spread of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for novel treatment options. Sodium new houttuyfonate (SNH) is an analogue of houttuynin, the main antibacterial ingredient of Houttuynia cordata Thunb. The aim of this study was to evaluate in vitro activity of SNH and its potential for synergy with antibiotics against hospital-associated MRSA. METHODOLOGY: A total of 103 MRSA clinical isolates recovered in two hospitals in Beijing were evaluated for susceptibility to SNH, oxacillin, cephalothin, meropenem, vancomycin, levofloxacin, minocycline, netilmicin, and trimethoprim/sulfamethoxazole by broth microdilution. Ten isolates were evaluated for potential for synergy between SNH and the antibiotics above by checkerboard assay. Time-kill analysis was performed in three isolates to characterize the kill kinetics of SNH alone and in combination with the antibiotics that engendered synergy in checkerboard assays. Besides, two reference strains were included in all assays. PRINCIPAL FINDINGS: SNH inhibited all test strains with minimum inhibitory concentrations (MICs) ranging from 16 to 64 µg/mL in susceptibility tests, and displayed inhibition to bacterial growth in concentration-dependent manner in time-kill analysis. In synergy studies, the combinations of SNH-oxacillin, SNH-cephalothin, SNH-meropenem and SNH-netilmicin showed synergistic effects against 12 MRSA strains with median fractional inhibitory concentration (FIC) indices of 0.38, 0.38, 0.25 and 0.38 in checkerboard assays. In time-kill analysis, SNH at 1/2 MIC in combination with oxacillin at 1/128 to 1/64 MIC or netilmicin at 1/8 to 1/2 MIC decreased the viable colonies by ≥2log(10) CFU/mL. CONCLUSIONS/SIGNIFICANCE: SNH demonstrated in vitro antibacterial activity against 103 hospital-associated MRSA isolates. Combinations of sub-MIC levels of SNH and oxacillin or netilmicin significantly improved the in vitro antibacterial activity against MRSA compared with either drug alone. The SNH-based combinations showed promise in combating MRSA.",2013 Jul 2,"['Lu, Xi', 'Yang, Xinyi', 'Li, Xue', 'Lu, Yun', 'Ren, Zhitao', 'Zhao, Longyin', 'Hu, Xinxin', 'Jiang, Jiandong', 'You, Xuefu']",PLoS One,,,False
fe82f6e8d1a8144c8d4de65cb971b8c96fb1cb57,PMC,In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus,http://dx.doi.org/10.1371/journal.pone.0068053,PMC3699466,23844154,CC BY,"BACKGROUND: Staphylococcus aureus can cause severe infections, including bacteremia and sepsis. The spread of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for novel treatment options. Sodium new houttuyfonate (SNH) is an analogue of houttuynin, the main antibacterial ingredient of Houttuynia cordata Thunb. The aim of this study was to evaluate in vitro activity of SNH and its potential for synergy with antibiotics against hospital-associated MRSA. METHODOLOGY: A total of 103 MRSA clinical isolates recovered in two hospitals in Beijing were evaluated for susceptibility to SNH, oxacillin, cephalothin, meropenem, vancomycin, levofloxacin, minocycline, netilmicin, and trimethoprim/sulfamethoxazole by broth microdilution. Ten isolates were evaluated for potential for synergy between SNH and the antibiotics above by checkerboard assay. Time-kill analysis was performed in three isolates to characterize the kill kinetics of SNH alone and in combination with the antibiotics that engendered synergy in checkerboard assays. Besides, two reference strains were included in all assays. PRINCIPAL FINDINGS: SNH inhibited all test strains with minimum inhibitory concentrations (MICs) ranging from 16 to 64 µg/mL in susceptibility tests, and displayed inhibition to bacterial growth in concentration-dependent manner in time-kill analysis. In synergy studies, the combinations of SNH-oxacillin, SNH-cephalothin, SNH-meropenem and SNH-netilmicin showed synergistic effects against 12 MRSA strains with median fractional inhibitory concentration (FIC) indices of 0.38, 0.38, 0.25 and 0.38 in checkerboard assays. In time-kill analysis, SNH at 1/2 MIC in combination with oxacillin at 1/128 to 1/64 MIC or netilmicin at 1/8 to 1/2 MIC decreased the viable colonies by ≥2log(10) CFU/mL. CONCLUSIONS/SIGNIFICANCE: SNH demonstrated in vitro antibacterial activity against 103 hospital-associated MRSA isolates. Combinations of sub-MIC levels of SNH and oxacillin or netilmicin significantly improved the in vitro antibacterial activity against MRSA compared with either drug alone. The SNH-based combinations showed promise in combating MRSA.",2013 Jul 2,"['Lu, Xi', 'Yang, Xinyi', 'Li, Xue', 'Lu, Yun', 'Ren, Zhitao', 'Zhao, Longyin', 'Hu, Xinxin', 'Jiang, Jiandong', 'You, Xuefu']",PLoS One,,,False
e6a9266f1f45099b19b5c4f3a4cf62de41786e54,PMC,The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Does Not Replicate in Syrian Hamsters,http://dx.doi.org/10.1371/journal.pone.0069127,PMC3699510,23844250,CC0,"In 2012 a novel coronavirus, MERS-CoV, associated with severe respiratory disease emerged in the Arabian Peninsula. To date, 55 human cases have been reported, including 31 fatal cases. Several of the cases were likely a result of human-to-human transmission. The emergence of this novel coronavirus prompts the need for a small animal model to study the pathogenesis of this virus and to test the efficacy of potential intervention strategies. In this study we explored the use of Syrian hamsters as a small animal disease model, using intratracheal inoculation and inoculation via aerosol. Clinical signs of disease, virus replication, histological lesions, cytokine upregulation nor seroconversion were observed in any of the inoculated animals, indicating that MERS-CoV does not replicate in Syrian hamsters.",2013 Jul 2,"['de Wit, Emmie', 'Prescott, Joseph', 'Baseler, Laura', 'Bushmaker, Trenton', 'Thomas, Tina', 'Lackemeyer, Matthew G.', 'Martellaro, Cynthia', 'Milne-Price, Shauna', 'Haddock, Elaine', 'Haagmans, Bart L.', 'Feldmann, Heinz', 'Munster, Vincent J.']",PLoS One,,,True
3e03474356ba4414f631c94959e3c22e8e239c49,PMC,Real-Time Fluorescence Loop Mediated Isothermal Amplification for the Detection of Acinetobacter baumannii,http://dx.doi.org/10.1371/journal.pone.0066406,PMC3699609,23843955,CC BY,"BACKGROUND: Detection of Acinetobacter baumannii has been relying primarily on bacterial culture that often fails to return useful results in time. Although DNA-based assays are more sensitive than bacterial culture in detecting the pathogen, the molecular results are often inconsistent and challenged by doubts on false positives, such as those due to system- and environment-derived contaminations. In addition, these molecular tools require expensive laboratory instruments. Therefore, establishing molecular tools for field use require simpler molecular platforms. The loop-mediated isothermal amplification method is relatively simple and can be improved for better use in a routine clinical bacteriology laboratory. A simple and portable device capable of performing both the amplification and detection (by fluorescence) of LAMP in the same platform has been developed in recent years. This method is referred to as real-time loop-mediated isothermal amplification. In this study, we attempted to utilize this method for rapid detection of A. baumannii. METHODOLOGY AND SIGNIFICANT FINDINGS: Species-specific primers were designed to test the utility of this method. Clinical samples of A. baumannii were used to determine the sensitivity and specificity of this system compared to bacterial culture and a polymerase chain reaction method. All positive samples isolated from sputum were confirmed to be the species of Acinetobacter by 16S rRNA gene sequencing. The RealAmp method was found to be simpler and allowed real-time detection of DNA amplification, and could distinguish A. baumannii from Acinetobacter calcoaceticus and Acinetobacter genomic species 3. DNA was extracted by simple boiling method. Compared to bacterial culture, the sensitivity and specificity of RealAmp in detecting A. baumannii was 98.9% and 75.0%, respectively. CONCLUSION: The RealAmp assay only requires a single unit, and the assay positivity can be verified by visual inspection. Therefore, this assay has great potential of field use as a molecular tool for detection of A. baumannii.",2013 Jul 2,"['Wang, Qinqin', 'Zhou, Yanbin', 'Li, Shaoli', 'Zhuo, Chao', 'Xu, Siqi', 'Huang, Lixia', 'Yang, Ling', 'Liao, Kang']",PLoS One,,,True
59d9ebaa6d9c6c4e8a89c831e0cbe7036e884887,PMC,NEWS,http://dx.doi.org/10.7189/jogh.03.010201,PMC3700025,,CC BY,,2013 Jun,,J Glob Health,,,False
9c983db27cc8ff3e50008d8d2bc803e14da7d38b,PMC,Mice with different susceptibility to tick-borne encephalitis virus infection show selective neutralizing antibody response and inflammatory reaction in the central nervous system,http://dx.doi.org/10.1186/1742-2094-10-77,PMC3700758,23805778,CC BY,"BACKGROUND: The clinical course of tick-borne encephalitis (TBE), a disease caused by TBE virus, ranges from asymptomatic or mild influenza-like infection to severe debilitating encephalitis or encephalomyelitis. Despite the medical importance of this disease, some crucial steps in the development of encephalitis remain poorly understood. In particular, the basis of the disease severity is largely unknown. METHODS: TBE virus growth, neutralizing antibody response, key cytokine and chemokine mRNA production and changes in mRNA levels of cell surface markers of immunocompetent cells in brain were measured in mice with different susceptibilities to TBE virus infection. RESULTS: An animal model of TBE based on BALB/c-c-STS/A (CcS/Dem) recombinant congenic mouse strains showing different severities of the infection in relation to the host genetic background was developed. After subcutaneous inoculation of TBE virus, BALB/c mice showed medium susceptibility to the infection, STS mice were resistant, and CcS-11 mice were highly susceptible. The resistant STS mice showed lower and delayed viremia, lower virus production in the brain and low cytokine/chemokine mRNA production, but had a strong neutralizing antibody response. The most sensitive strain (CcS-11) failed in production of neutralizing antibodies, but exhibited strong cytokine/chemokine mRNA production in the brain. After intracerebral inoculation, all mouse strains were sensitive to the infection and had similar virus production in the brain, but STS mice survived significantly longer than CcS-11 mice. These two strains also differed in the expression of key cytokines/chemokines, particularly interferon gamma-induced protein 10 (IP-10/CXCL10) and monocyte chemotactic protein-1 (MCP-1/CCL2) in the brain. CONCLUSIONS: Our data indicate that the genetic control is an important factor influencing the clinical course of TBE. High neutralizing antibody response might be crucial for preventing host fatality, but high expression of various cytokines/chemokines during TBE can mediate immunopathology and be associated with more severe course of the infection and increased fatality.",2013 Jun 27,"['Palus, Martin', 'Vojtíšková, Jarmila', 'Salát, Jiří', 'Kopecký, Jan', 'Grubhoffer, Libor', 'Lipoldová, Marie', 'Demant, Peter', 'Růžek, Daniel']",J Neuroinflammation,,,True
0309a2f31c4344e9eecfedea296771452f62e8df,PMC,Mice with different susceptibility to tick-borne encephalitis virus infection show selective neutralizing antibody response and inflammatory reaction in the central nervous system,http://dx.doi.org/10.1186/1742-2094-10-77,PMC3700758,23805778,CC BY,"BACKGROUND: The clinical course of tick-borne encephalitis (TBE), a disease caused by TBE virus, ranges from asymptomatic or mild influenza-like infection to severe debilitating encephalitis or encephalomyelitis. Despite the medical importance of this disease, some crucial steps in the development of encephalitis remain poorly understood. In particular, the basis of the disease severity is largely unknown. METHODS: TBE virus growth, neutralizing antibody response, key cytokine and chemokine mRNA production and changes in mRNA levels of cell surface markers of immunocompetent cells in brain were measured in mice with different susceptibilities to TBE virus infection. RESULTS: An animal model of TBE based on BALB/c-c-STS/A (CcS/Dem) recombinant congenic mouse strains showing different severities of the infection in relation to the host genetic background was developed. After subcutaneous inoculation of TBE virus, BALB/c mice showed medium susceptibility to the infection, STS mice were resistant, and CcS-11 mice were highly susceptible. The resistant STS mice showed lower and delayed viremia, lower virus production in the brain and low cytokine/chemokine mRNA production, but had a strong neutralizing antibody response. The most sensitive strain (CcS-11) failed in production of neutralizing antibodies, but exhibited strong cytokine/chemokine mRNA production in the brain. After intracerebral inoculation, all mouse strains were sensitive to the infection and had similar virus production in the brain, but STS mice survived significantly longer than CcS-11 mice. These two strains also differed in the expression of key cytokines/chemokines, particularly interferon gamma-induced protein 10 (IP-10/CXCL10) and monocyte chemotactic protein-1 (MCP-1/CCL2) in the brain. CONCLUSIONS: Our data indicate that the genetic control is an important factor influencing the clinical course of TBE. High neutralizing antibody response might be crucial for preventing host fatality, but high expression of various cytokines/chemokines during TBE can mediate immunopathology and be associated with more severe course of the infection and increased fatality.",2013 Jun 27,"['Palus, Martin', 'Vojtíšková, Jarmila', 'Salát, Jiří', 'Kopecký, Jan', 'Grubhoffer, Libor', 'Lipoldová, Marie', 'Demant, Peter', 'Růžek, Daniel']",J Neuroinflammation,,,False
3380c2147c090bd81525c67d4200fb3860517008,PMC,Intranasally Administered Antigen 85B Gene Vaccine in Non-Replicating Human Parainfluenza Type 2 Virus Vector Ameliorates Mouse Atopic Dermatitis,http://dx.doi.org/10.1371/journal.pone.0066614,PMC3701015,23843958,CC BY,"Atopic dermatitis (AD) is a refractory and recurrent inflammatory skin disease. Various factors including heredity, environmental agent, innate and acquired immunity, and skin barrier function participate in the pathogenesis of AD. T -helper (Th) 2-dominant immunological milieu has been suggested in the acute phase of AD. Antigen 85B (Ag85B) is a 30-kDa secretory protein well conserved in Mycobacterium species. Ag85B has strong Th1-type cytokine inducing activity, and is expected to ameliorate Th2 condition in allergic disease. To perform Ag85B function in vivo, effective and less invasive vaccination method is required. Recently, we have established a novel functional virus vector; recombinant human parainfluenza type 2 virus vector (rhPIV2): highly expressive, replication-deficient, and very low-pathogenic vector. In this study, we investigated the efficacy of rhPIV2 engineered to express Ag85B (rhPIV2/Ag85B) in a mouse AD model induced by repeated oxazolone (OX) challenge. Ear swelling, dermal cell infiltrations and serum IgE level were significantly suppressed in the rhPIV2/Ag85B treated mouse group accompanied with elevated IFN-γ and IL-10 mRNA expressions, and suppressed IL-4, TNF-α and MIP-2 mRNA expressions. The treated mice showed no clinical symptom of croup or systemic adverse reactions. The respiratory tract epithelium captured rhPIV2 effectively without remarkable cytotoxic effects. These results suggested that rhPIV2/Ag85B might be a potent therapeutic tool to control allergic disorders.",2013 Jul 3,"['Kitagawa, Hiroshi', 'Kawano, Mitsuo', 'Yamanaka, Keiichi', 'Kakeda, Masato', 'Tsuda, Kenshiro', 'Inada, Hiroyasu', 'Yoneda, Misao', 'Sakaguchi, Tadashi', 'Nigi, Akina', 'Nishimura, Koumei', 'Komada, Hiroshi', 'Tsurudome, Masato', 'Yasutomi, Yasuhiro', 'Nosaka, Tetsuya', 'Mizutani, Hitoshi']",PLoS One,,,True
06ebe6e32a2e7241e23d3fb51c4dffeed389861d,PMC,Modelling the transmission of healthcare associated infections: a systematic review,http://dx.doi.org/10.1186/1471-2334-13-294,PMC3701468,23809195,CC BY,"BACKGROUND: Dynamic transmission models are increasingly being used to improve our understanding of the epidemiology of healthcare-associated infections (HCAI). However, there has been no recent comprehensive review of this emerging field. This paper summarises how mathematical models have informed the field of HCAI and how methods have developed over time. METHODS: MEDLINE, EMBASE, Scopus, CINAHL plus and Global Health databases were systematically searched for dynamic mathematical models of HCAI transmission and/or the dynamics of antimicrobial resistance in healthcare settings. RESULTS: In total, 96 papers met the eligibility criteria. The main research themes considered were evaluation of infection control effectiveness (64%), variability in transmission routes (7%), the impact of movement patterns between healthcare institutes (5%), the development of antimicrobial resistance (3%), and strain competitiveness or co-colonisation with different strains (3%). Methicillin-resistant Staphylococcus aureus was the most commonly modelled HCAI (34%), followed by vancomycin resistant enterococci (16%). Other common HCAIs, e.g. Clostridum difficile, were rarely investigated (3%). Very few models have been published on HCAI from low or middle-income countries. The first HCAI model has looked at antimicrobial resistance in hospital settings using compartmental deterministic approaches. Stochastic models (which include the role of chance in the transmission process) are becoming increasingly common. Model calibration (inference of unknown parameters by fitting models to data) and sensitivity analysis are comparatively uncommon, occurring in 35% and 36% of studies respectively, but their application is increasing. Only 5% of models compared their predictions to external data. CONCLUSIONS: Transmission models have been used to understand complex systems and to predict the impact of control policies. Methods have generally improved, with an increased use of stochastic models, and more advanced methods for formal model fitting and sensitivity analyses. Insights gained from these models could be broadened to a wider range of pathogens and settings. Improvements in the availability of data and statistical methods could enhance the predictive ability of models.",2013 Jun 28,"['van Kleef, Esther', 'Robotham, Julie V', 'Jit, Mark', 'Deeny, Sarah R', 'Edmunds, William J']",BMC Infect Dis,,,True
22e6bf7b64a17d055dca239d9fdac04edfb1414c,PMC,Emerging Infectious Diseases: Threats to Human Health and Global Stability,http://dx.doi.org/10.1371/journal.ppat.1003467,PMC3701702,23853589,CC0,,2013 Jul 4,"['Morens, David M.', 'Fauci, Anthony S.']",PLoS Pathog,,,True
cf4b53e86101ba9279f53b315f8aee6ecba9e0c0,PMC,"What we are watching—five top global infectious disease threats, 2012: a perspective from CDC’s Global Disease Detection Operations Center",http://dx.doi.org/10.3402/ehtj.v6i0.20632,PMC3701798,23827387,CC BY,"Disease outbreaks of international public health importance continue to occur regularly; detecting and tracking significant new public health threats in countries that cannot or might not report such events to the global health community is a challenge. The Centers for Disease Control and Prevention’s (CDC) Global Disease Detection (GDD) Operations Center, established in early 2007, monitors infectious and non-infectious public health events to identify new or unexplained global public health threats and better position CDC to respond, if public health assistance is requested or required. At any one time, the GDD Operations Center actively monitors approximately 30–40 such public health threats; here we provide our perspective on five of the top global infectious disease threats that we were watching in 2012: (1) avian influenza A (H5N1), (2) cholera, (3) wild poliovirus, (4) enterovirus-71, and (5) extensively drug-resistant tuberculosis.",2013 Jul 3,"['Christian, Kira A.', 'Ijaz, Kashef', 'Dowell, Scott F.', 'Chow, Catherine C.', 'Chitale, Rohit A.', 'Bresee, Joseph S.', 'Mintz, Eric', 'Pallansch, Mark A.', 'Wassilak, Steven', 'McCray, Eugene', 'Arthur, Ray R.']",Emerg Health Threats J,,,True
70945e1b77b2dd46582a7d73d30746432f209f0d,PMC,Alberta family physicians’ willingness to work during an influenza pandemic: a cross-sectional study,http://dx.doi.org/10.1186/1447-056X-12-3,PMC3702417,23800113,CC BY,"OBJECTIVE: Effective pandemic responses rely on frontline healthcare workers continuing to work despite increased risk to themselves. Our objective was to investigate Alberta family physicians willingness to work during an influenza pandemic. Design: Cross-sectional survey. Setting: Alberta prior to the fall wave of the H1N1 epidemic. Participants: 192 participants from a random sample of 1000 Alberta family physicians stratified by region. Main Outcome Measures: Willingness to work through difficult scenarios created by an influenza epidemic. RESULTS: The corrected response rate was 22%. The most physicians who responded were willing to continue working through some scenarios caused by a pandemic, but in other circumstances less than 50% would continue. Men were more willing to continue working than women. In some situations South African and British trained physicians were more willing to continue working than other groups. CONCLUSIONS: Although many physicians intend to maintain their practices in the event of a pandemic, in some circumstances fewer are willing to work. Pandemic preparation requires ensuring a workforce is available. Healthcare systems must provide frontline healthcare workers with the support and resources they need to enable them to continue providing care.",2013 Jun 26,"['Dickinson, James A', 'Bani-Adam, Gisoo', 'Williamson, Tyler', 'Berzins, Sandy', 'Pearce, Craig', 'Ricketson, Leah', 'Medd, Emily']",Asia Pac Fam Med,,,True
1e7e3df5deec55ed5c2fa7f9cba8854c6aeb7ab6,PMC,The incidence and aetiology of hospitalised community-acquired pneumonia among Vietnamese adults: a prospective surveillance in Central Vietnam,http://dx.doi.org/10.1186/1471-2334-13-296,PMC3702433,23815298,CC BY,"BACKGROUND: Lower respiratory tract infection (LRTI) including Community-acquired pneumonia (CAP) is a common infectious disease that is associated with significant morbidity and mortality. The patterns of aetiological pathogens differ by region and country. Special attention must be paid to CAP in Southeast Asia (SEA), a region facing rapid demographic transition. Estimates burden and aetiological patterns of CAP are essential for the clinical and public health management. The purposes of the study are to determine the incidence, aetiological pathogens, clinical pictures and risk factors of community-acquired pneumonia (CAP) in the Vietnamese adult population. METHODS: A prospective surveillance for hospitalised adult CAP was conducted in Khanh Hoa Province, Central Vietnam. All adults aged ≥15 years with lower respiratory tract infections (LRTI) admitted to a provincial hospital from September 2009 to August 2010 were enrolled in the study. Patients were classified into CAP and non-pneumonic LRTI (NPLRTI) according to the radiological findings. Bacterial pathogens were identified from sputum samples by the conventional culture and polymerase chain reaction (PCR) for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis; 13 respiratory viruses were identified from nasopharyngeal specimens by PCR. RESULTS: Of all 367 LRTI episodes examined, 174 (47%) were CAP. Older age, the presence of underlying respiratory conditions, and higher index score of smoking were associated with CAP. The one-year estimated incidence of hospitalised adult CAP in our study population was 0.81 per 1,000 person years. The incidence increased considerably with age and was highest among the elderly. The case fatality proportion of hospitalised CAP patients was 9.8%. Among 286 sputum samples tested for bacterial PCR, 79 (28%) were positive for H. influenzae, and 65 (23%) were positive for S. pneumoniae. Among 357 samples tested for viral PCR, 73 (21%) were positive for respiratory viruses; influenza A (n = 32, 9%) was the most common. CONCLUSIONS: The current adult CAP incidence in Vietnam was relatively low; this result was mainly attributed to the young age of our study population.",2013 Jul 1,"['Takahashi, Kensuke', 'Suzuki, Motoi', 'Minh, Le Nhat', 'Anh, Nguyen Hien', 'Huong, Luu Thi Minh', 'Son, Tran Vo Vinh', 'Long, Phan The', 'Ai, Nguyen Thi Thuy', 'Tho, Le Huu', 'Morimoto, Konosuke', 'Kilgore, Paul E', 'Anh, Dang Duc', 'Ariyoshi, Koya', 'Yoshida, Lay Myint']",BMC Infect Dis,,,True
ae29a35ad6b9e4267e1d965b523a6b72cb2c088c,PMC,Major Histocompatibility Complex Class I Haplotype Diversity in Chinese Rhesus Macaques,http://dx.doi.org/10.1534/g3.113.006254,PMC3704247,23696100,CC BY,"The use of Chinese-origin rhesus macaques (Macaca mulatta) for infectious disease immunity research is increasing despite the relative lack of major histocompatibility complex (MHC) class I immunogenetics information available for this population. We determined transcript-based MHC class I haplotypes for 385 Chinese rhesus macaques from five different experimental cohorts, providing a concise representation of the full complement of MHC class I major alleles expressed by each animal. In total, 123 Mamu-A and Mamu-B haplotypes were defined in the full Chinese rhesus macaque cohort. We then performed an analysis of haplotype frequencies across the experimental cohorts of Chinese rhesus macaques, as well as a comparison against a group of 96 Indian rhesus macaques. Notably, 35 of the 51 Mamu-A and Mamu-B haplotypes observed in Indian rhesus macaques were also detected in the Chinese population, with 85% of the 385 Chinese-origin rhesus macaques expressing at least one of these class I haplotypes. This unexpected conservation of Indian rhesus macaque MHC class I haplotypes in the Chinese rhesus macaque population suggests that immunologic insights originally gleaned from studies using Indian rhesus macaques may be more applicable to Chinese rhesus macaques than previously appreciated and may provide an opportunity for studies of CD8(+) T-cell responses between populations. It may also be possible to extend these studies across multiple species of macaques, as we found evidence of shared ancestral haplotypes between Chinese rhesus and Mauritian cynomolgus macaques.",2013 Jul 1,"['Karl, Julie A.', 'Bohn, Patrick S.', 'Wiseman, Roger W.', 'Nimityongskul, Francesca A.', 'Lank, Simon M.', 'Starrett, Gabriel J.', 'O’Connor, David H.']",G3 (Bethesda),,,True
9043919dae5100888c661ef0c5c24d144fdf4351,PMC,Major Histocompatibility Complex Class I Haplotype Diversity in Chinese Rhesus Macaques,http://dx.doi.org/10.1534/g3.113.006254,PMC3704247,23696100,CC BY,"The use of Chinese-origin rhesus macaques (Macaca mulatta) for infectious disease immunity research is increasing despite the relative lack of major histocompatibility complex (MHC) class I immunogenetics information available for this population. We determined transcript-based MHC class I haplotypes for 385 Chinese rhesus macaques from five different experimental cohorts, providing a concise representation of the full complement of MHC class I major alleles expressed by each animal. In total, 123 Mamu-A and Mamu-B haplotypes were defined in the full Chinese rhesus macaque cohort. We then performed an analysis of haplotype frequencies across the experimental cohorts of Chinese rhesus macaques, as well as a comparison against a group of 96 Indian rhesus macaques. Notably, 35 of the 51 Mamu-A and Mamu-B haplotypes observed in Indian rhesus macaques were also detected in the Chinese population, with 85% of the 385 Chinese-origin rhesus macaques expressing at least one of these class I haplotypes. This unexpected conservation of Indian rhesus macaque MHC class I haplotypes in the Chinese rhesus macaque population suggests that immunologic insights originally gleaned from studies using Indian rhesus macaques may be more applicable to Chinese rhesus macaques than previously appreciated and may provide an opportunity for studies of CD8(+) T-cell responses between populations. It may also be possible to extend these studies across multiple species of macaques, as we found evidence of shared ancestral haplotypes between Chinese rhesus and Mauritian cynomolgus macaques.",2013 Jul 1,"['Karl, Julie A.', 'Bohn, Patrick S.', 'Wiseman, Roger W.', 'Nimityongskul, Francesca A.', 'Lank, Simon M.', 'Starrett, Gabriel J.', 'O’Connor, David H.']",G3 (Bethesda),,,False
d9b1b94a99f1843613b257218f8b5af4fcb2d38c,PMC,Major Histocompatibility Complex Class I Haplotype Diversity in Chinese Rhesus Macaques,http://dx.doi.org/10.1534/g3.113.006254,PMC3704247,23696100,CC BY,"The use of Chinese-origin rhesus macaques (Macaca mulatta) for infectious disease immunity research is increasing despite the relative lack of major histocompatibility complex (MHC) class I immunogenetics information available for this population. We determined transcript-based MHC class I haplotypes for 385 Chinese rhesus macaques from five different experimental cohorts, providing a concise representation of the full complement of MHC class I major alleles expressed by each animal. In total, 123 Mamu-A and Mamu-B haplotypes were defined in the full Chinese rhesus macaque cohort. We then performed an analysis of haplotype frequencies across the experimental cohorts of Chinese rhesus macaques, as well as a comparison against a group of 96 Indian rhesus macaques. Notably, 35 of the 51 Mamu-A and Mamu-B haplotypes observed in Indian rhesus macaques were also detected in the Chinese population, with 85% of the 385 Chinese-origin rhesus macaques expressing at least one of these class I haplotypes. This unexpected conservation of Indian rhesus macaque MHC class I haplotypes in the Chinese rhesus macaque population suggests that immunologic insights originally gleaned from studies using Indian rhesus macaques may be more applicable to Chinese rhesus macaques than previously appreciated and may provide an opportunity for studies of CD8(+) T-cell responses between populations. It may also be possible to extend these studies across multiple species of macaques, as we found evidence of shared ancestral haplotypes between Chinese rhesus and Mauritian cynomolgus macaques.",2013 Jul 1,"['Karl, Julie A.', 'Bohn, Patrick S.', 'Wiseman, Roger W.', 'Nimityongskul, Francesca A.', 'Lank, Simon M.', 'Starrett, Gabriel J.', 'O’Connor, David H.']",G3 (Bethesda),,,False
9c3004ec902e954fcf2cb0b8a906cc7e8394ec79,PMC,Major Histocompatibility Complex Class I Haplotype Diversity in Chinese Rhesus Macaques,http://dx.doi.org/10.1534/g3.113.006254,PMC3704247,23696100,CC BY,"The use of Chinese-origin rhesus macaques (Macaca mulatta) for infectious disease immunity research is increasing despite the relative lack of major histocompatibility complex (MHC) class I immunogenetics information available for this population. We determined transcript-based MHC class I haplotypes for 385 Chinese rhesus macaques from five different experimental cohorts, providing a concise representation of the full complement of MHC class I major alleles expressed by each animal. In total, 123 Mamu-A and Mamu-B haplotypes were defined in the full Chinese rhesus macaque cohort. We then performed an analysis of haplotype frequencies across the experimental cohorts of Chinese rhesus macaques, as well as a comparison against a group of 96 Indian rhesus macaques. Notably, 35 of the 51 Mamu-A and Mamu-B haplotypes observed in Indian rhesus macaques were also detected in the Chinese population, with 85% of the 385 Chinese-origin rhesus macaques expressing at least one of these class I haplotypes. This unexpected conservation of Indian rhesus macaque MHC class I haplotypes in the Chinese rhesus macaque population suggests that immunologic insights originally gleaned from studies using Indian rhesus macaques may be more applicable to Chinese rhesus macaques than previously appreciated and may provide an opportunity for studies of CD8(+) T-cell responses between populations. It may also be possible to extend these studies across multiple species of macaques, as we found evidence of shared ancestral haplotypes between Chinese rhesus and Mauritian cynomolgus macaques.",2013 Jul 1,"['Karl, Julie A.', 'Bohn, Patrick S.', 'Wiseman, Roger W.', 'Nimityongskul, Francesca A.', 'Lank, Simon M.', 'Starrett, Gabriel J.', 'O’Connor, David H.']",G3 (Bethesda),,,False
98c2af7070735431908c6d271df6b49f01924f96,PMC,Antiviral Type I and Type III Interferon Responses in the Central Nervous System,http://dx.doi.org/10.3390/v5030834,PMC3705299,23503326,CC BY,"The central nervous system (CNS) harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB) from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs) are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i) preventing neuroinvasion and infection of CNS cells; ii) the identity of IFN-producing cells in the CNS; iii) the antiviral activity of ISGs; and iv) the activity of viral proteins of neurotropic viruses that target the IFN pathway.",2013 Mar 15,"['Sorgeloos, Frédéric', 'Kreit, Marguerite', 'Hermant, Pascale', 'Lardinois, Cécile', 'Michiels, Thomas']",Viruses,,,True
e4281a03ae26dbf7a445f1697dde5b4352fec07b,PMC,"Baicalein, Ethyl Acetate, and Chloroform Extracts of Scutellaria baicalensis Inhibit the Neuraminidase Activity of Pandemic 2009 H1N1 and Seasonal Influenza A Viruses",http://dx.doi.org/10.1155/2013/750803,PMC3705751,23864896,CC BY,"This study rated antiviral activity of Scutellaria baicalensis Georgi (S. baicalensis) extracts against influenza A virus subtypes, for example, pandemic 2009 H1N1, seasonal H1N1 and H3N2. Ethyl acetate (EtOAc) and chloroform extracts inhibited in vitro neuraminidase (NA) enzymatic activity and viral replication more than methanol (MeOH) extract. EtOAc extract demonstrated NA inhibition IC(50) values ranging from 73.16 to 487.40 μg/mL and plaque reduction IC(50) values ranging from 23.7 to 27.4 μg/mL. Chloroform extract showed antiviral activities with plaque reduction IC(50) values ranging from 14.16 to 41.49 μg/mL Time-of-addition assay indicated that EtOAc and chloroform extracts also significantly inhibited virus yields after infection. HPLC analysis demonstrated that baicalin was dominant in the MeOH extract; baicalein and chrysin were rich in the EtOAc and chloroform extracts. Molecular simulation revealed baicalein hydrogen bonding with Glu277 as well as hydrophobic and Van der Waals interactions with Ile222, Arg224, Ser246, and Tyr347 in NA1 active sites of NA1. Baicalein inhibited in vitro replication of influenza A viruses pandemic 2009 H1N1 (IC(50) = 0.018 μM) and seasonal 2007 H1N1 using plaque reduction assays. A combination of low-dose baicalein with other anti-influenza agents could be applicable for development of alternative remedies treating influenza A virus infection.",2013 Jun 20,"['Hour, Mann-Jen', 'Huang, Su-Hua', 'Chang, Ching-Yao', 'Lin, Yen-Kuan', 'Wang, Ching-Ying', 'Chang, Yuan-Shiun', 'Lin, Cheng-Wen']",Evid Based Complement Alternat Med,,,True
d540410f675824bd89408b309c4502279483cbe3,PMC,Microglia Play a Major Role in Direct Viral-Induced Demyelination,http://dx.doi.org/10.1155/2013/510396,PMC3705805,23864878,CC BY,"Microglia are the resident macrophage-like populations in the central nervous system (CNS). Microglia remain quiescent, unable to perform effector and antigen presentation (APC) functions until activated by injury or infection, and have been suggested to represent the first line of defence for the CNS. Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS). Current studies revealed that MHV infection is associated with the pronounced activation of microglia during acute inflammation, as evidenced by characteristic changes in cellular morphology and increased expression of microglia-specific proteins, Iba1 (ionized calcium-binding adaptor molecule 1), which is a macrophage/microglia-specific novel calcium-binding protein and involved in membrane ruffling and phagocytosis. During chronic inflammation (day 30 postinfection), microglia were still present within areas of demyelination. Experiments performed in ex vivo spinal cord slice culture and in vitro neonatal microglial culture confirmed direct microglial infection. Our results suggest that MHV can directly infect and activate microglia during acute inflammation, which in turn during chronic inflammation stage causes phagocytosis of myelin sheath leading to chronic inflammatory demyelination.",2013 Jun 20,"['Chatterjee, Dhriti', 'Biswas, Kaushiki', 'Nag, Soma', 'Ramachandra, S. G.', 'Das Sarma, Jayasri']",Clin Dev Immunol,,,False
45ceff2a130c98717dcd6984a2fec10e86575c91,PMC,Microglia Play a Major Role in Direct Viral-Induced Demyelination,http://dx.doi.org/10.1155/2013/510396,PMC3705805,23864878,CC BY,"Microglia are the resident macrophage-like populations in the central nervous system (CNS). Microglia remain quiescent, unable to perform effector and antigen presentation (APC) functions until activated by injury or infection, and have been suggested to represent the first line of defence for the CNS. Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS). Current studies revealed that MHV infection is associated with the pronounced activation of microglia during acute inflammation, as evidenced by characteristic changes in cellular morphology and increased expression of microglia-specific proteins, Iba1 (ionized calcium-binding adaptor molecule 1), which is a macrophage/microglia-specific novel calcium-binding protein and involved in membrane ruffling and phagocytosis. During chronic inflammation (day 30 postinfection), microglia were still present within areas of demyelination. Experiments performed in ex vivo spinal cord slice culture and in vitro neonatal microglial culture confirmed direct microglial infection. Our results suggest that MHV can directly infect and activate microglia during acute inflammation, which in turn during chronic inflammation stage causes phagocytosis of myelin sheath leading to chronic inflammatory demyelination.",2013 Jun 20,"['Chatterjee, Dhriti', 'Biswas, Kaushiki', 'Nag, Soma', 'Ramachandra, S. G.', 'Das Sarma, Jayasri']",Clin Dev Immunol,,,False
7107f088cbed45d8a06a026276ccf4d602d50f10,PMC,Microglia Play a Major Role in Direct Viral-Induced Demyelination,http://dx.doi.org/10.1155/2013/510396,PMC3705805,23864878,CC BY,"Microglia are the resident macrophage-like populations in the central nervous system (CNS). Microglia remain quiescent, unable to perform effector and antigen presentation (APC) functions until activated by injury or infection, and have been suggested to represent the first line of defence for the CNS. Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS). Current studies revealed that MHV infection is associated with the pronounced activation of microglia during acute inflammation, as evidenced by characteristic changes in cellular morphology and increased expression of microglia-specific proteins, Iba1 (ionized calcium-binding adaptor molecule 1), which is a macrophage/microglia-specific novel calcium-binding protein and involved in membrane ruffling and phagocytosis. During chronic inflammation (day 30 postinfection), microglia were still present within areas of demyelination. Experiments performed in ex vivo spinal cord slice culture and in vitro neonatal microglial culture confirmed direct microglial infection. Our results suggest that MHV can directly infect and activate microglia during acute inflammation, which in turn during chronic inflammation stage causes phagocytosis of myelin sheath leading to chronic inflammatory demyelination.",2013 Jun 20,"['Chatterjee, Dhriti', 'Biswas, Kaushiki', 'Nag, Soma', 'Ramachandra, S. G.', 'Das Sarma, Jayasri']",Clin Dev Immunol,,,True
25d8592c8527ce05463209c6e0c3f61c75b65f86,PMC,"Febrile neutropenia: significance of elaborated screening for respiratory viruses, and the comparison of different sampling methods, in neutropenic patients with hematological malignancies",http://dx.doi.org/10.1186/1743-422X-10-212,PMC3706282,23805898,CC BY,"BACKGROUND: During febrile neutropenia in only 30 to 60 percent an infectious agent is identified. This diagnostic gap could hypothetically be reduced with the broad implementation of molecular detection techniques like PCR, which has revolutionized the detection of infectious diseases during the last two decades. FINDINGS: We performed a longitudinal prospective study (N = 81) of neutropenic patients to assess the role of respiratory viruses in neutropenic fever and to determine the clinical relevance of blind screening for these viruses. Respiratory viruses were recovered in 14% of the patients prior to neutropenia. In 13% of neutropenic patients without fever and in 19% of those with fever, a respiratory virus was detected. Comparing different sample types; nasal swabs performed significantly better (16/117 = 43%), than throat swabs (6/106 = 6%). Throat gurgles did not show significant differences from the latter sample types. CONCLUSIONS: Blind diagnostic screening for respiratory viruses before or during neutropenia is not useful. Nasal swabs are sensitive and practical option for screening on respiratory viruses.",2013 Jun 27,"['Jansen, Rogier R', 'Biemond, Bart J', 'Schinkel, Janke', 'Koekkoek, Sylvie M', 'Molenkamp, Richard', 'de Jong, Menno D', 'Visser, Caroline E']",Virol J,,,True
b454887997af026ed0589fcb18e59aed44473e1d,PMC,Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish,http://dx.doi.org/10.1371/journal.pone.0068759,PMC3706321,23874753,CC BY,"Understanding spatial distribution and dynamics of receptors within unperturbed membranes is essential for elucidating their role in antiviral signaling, but conventional studies of detergent-resistant membrane fractions cannot provide this information. Caveolae are integral to numerous signaling pathways and these membrane domains have been previously implicated in viral entry but not antiviral defense. This study shows, for the first time, the importance of spatio-temporal regulation of signaling receptors and the importance of the regulation of clustering for downstream signaling. A novel mechanism for virus evasion of host cell defenses is demonstrated through disruption of clusters of signaling molecules organized within caveolin-rich domains. Viral infection leads to a downregulation in Caveolin-1b (Cav-1b), disrupting clusters of CRFB1, a zebrafish type I interferon receptor (–R) subunit. Super-resolution microscopy has enabled the first single-molecule imaging of CRFB1 association with cav-1b-containing membrane domains. Strikingly, downregulation of Cav-1b, the major protein component of caveolae, caused CRFB1 clusters to disperse. Dispersal of CRFB1 clusters led to a suppressed antiviral immune response both in vitro and in vivo, through abrogation of downstream signaling. This response strongly suggests that CRFB1 organization within cav-1b-containing membrane domains is critical for IFN-mediated antiviral defense and presents a previously undescribed antiviral evasion strategy to alter IFN signaling and the antiviral immune response.",2013 Jul 9,"['Gabor, Kristin A.', 'Stevens, Chad R.', 'Pietraszewski, Matthew J.', 'Gould, Travis J.', 'Shim, Juyoung', 'Yoder, Jeffrey A.', 'Lam, Siew Hong', 'Gong, Zhiyuan', 'Hess, Samuel T.', 'Kim, Carol H.']",PLoS One,,,True
4c7ae8ea3cf737fe457b191ae7a7dc2fcaee44bf,PMC,Hepatitis C Virus Non-Structural Protein 3 Interacts with Cytosolic 5′(3′)-Deoxyribonucleotidase and Partially Inhibits Its Activity,http://dx.doi.org/10.1371/journal.pone.0068736,PMC3706368,23874742,CC BY,"Infection with hepatitis C virus (HCV) is etiologically involved in liver cirrhosis, hepatocellular carcinoma and B-cell lymphomas. It has been demonstrated previously that HCV non-structural protein 3 (NS3) is involved in cell transformation. In this study, a yeast two-hybrid screening experiment was conducted to identify cellular proteins interacting with HCV NS3 protein. Cytosolic 5′(3′)-deoxyribonucleotidase (cdN, dNT-1) was found to interact with HCV NS3 protein. Binding domains of HCV NS3 and cellular cdN proteins were also determined using the yeast two-hybrid system. Interactions between HCV NS3 and cdN proteins were further demonstrated by co-immunoprecipitation and confocal analysis in cultured cells. The cellular cdN activity was partially repressed by NS3 protein in both the transiently-transfected and the stably-transfected systems. Furthermore, HCV partially repressed the cdN activity while had no effect on its protein expression in the systems of HCV sub-genomic replicons and infectious HCV virions. Deoxyribonucleotidases are present in most mammalian cells and involve in the regulation of intracellular deoxyribonucleotides pools by substrate cycles. Control of DNA precursor concentration is essential for the maintenance of genetic stability. Reduction of cdN activity would result in the imbalance of DNA precursor concentrations. Thus, our results suggested that HCV partially reduced the cdN activity via its NS3 protein and this may in turn cause diseases.",2013 Jul 9,"['Fang, Chiu-Ping', 'Li, Zhi-Cheng', 'Yang, Chee-Hing', 'Cheng, Ju-Chien', 'Yeh, Yung-Ju', 'Sun, Tsai-Hsia', 'Li, Hui-Chun', 'Juang, Yue-Li', 'Lo, Shih-Yen']",PLoS One,,,True
235451b60cac00666f0e69e9d196d090da8609a5,PMC,Effects of Nasal or Pulmonary Delivered Treatments with an Adenovirus Vectored Interferon (mDEF201) on Respiratory and Systemic Infections in Mice Caused by Cowpox and Vaccinia Viruses,http://dx.doi.org/10.1371/journal.pone.0068685,PMC3706414,23874722,CC BY,"An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201) was evaluated for efficacy against lethal cowpox (Brighton strain) and vaccinia (WR strain) virus respiratory and systemic infections in mice. Two routes of mDEF201 administration were used, nasal sinus (5-µl) and pulmonary (50-µl), to compare differences in efficacy, since the preferred treatment of humans would be in a relatively small volume delivered intranasally. Lower respiratory infections (LRI), upper respiratory infections (URI), and systemic infections were induced by 50-µl intranasal, 10-µl intranasal, and 100-µl intraperitoneal virus challenges, respectively. mDEF201 treatments were given prophylactically either 24 h (short term) or 56d (long-term) prior to virus challenge. Single nasal sinus treatments of 10(6) and 10(7) PFU/mouse of mDEF201 protected all mice from vaccinia-induced LRI mortality (comparable to published studies with pulmonary delivered mDEF201). Systemic vaccinia infections responded significantly better to nasal sinus delivered mDEF201 than to pulmonary treatments. Cowpox LRI infections responded to 10(7) mDEF201 treatments, but a 10(6) dose was only weakly protective. Cowpox URI infections were equally treatable by nasal sinus and pulmonary delivered mDEF201 at 10(7) PFU/mouse. Dose-responsive prophylaxis with mDEF201, given one time only 56 d prior to initiating a vaccinia virus LRI infection, was 100% protective from 10(5) to 10(7) PFU/mouse. Improvements in lung hemorrhage score and lung weight were evident, as were decreases in liver, lung, and spleen virus titers. Thus, mDEF201 was able to treat different vaccinia and cowpox virus infections using both nasal sinus and pulmonary treatment regimens, supporting its development for humans.",2013 Jul 9,"['Smee, Donald F.', 'Wong, Min-Hui', 'Hurst, Brett L.', 'Ennis, Jane', 'Turner, Jeffrey D.']",PLoS One,,,True
7862ffdcf951e5860a7e3dc66c9d3b07f5fbc281,PMC,A Functional Promoter Polymorphism of IFITM3 Is Associated with Susceptibility to Pediatric Tuberculosis in Han Chinese Population,http://dx.doi.org/10.1371/journal.pone.0067816,PMC3706438,23874452,CC BY,"A susceptibility locus for tuberculosis, a re-emerging infectious disease throughout the world, was previously discovered to exist on chromosome 11p15. IFITM3 gene encoding for interferon inducible transmembrane protein 3, is located at 11p15. It acts as an effector molecule for interferon-gamma, which is essential for anti-tuberculosis immune response. In order to investigate the association between susceptibility to TB and genetic polymorphisms of the IFITM3 core promoter, a case-control study including 368 TB patients and 794 healthy controls was performed in Han Chinese children in northern China. The rs3888188 polymorphism showed significant association with susceptibility to TB. The rs3888188 G allele, acting recessively, was more frequent in TB patients (95% confidence interval: 1.08–1.56, Bonferroni P-value: 0.039). We further assessed the effect of rs3888188 polymorphism on IFITM3 transcription in vitro. As based on luciferase promoter assays, the promoter activity of haplotypes with rs3888188 G allele was lower than that of haplotypes with rs3888188 T allele. Moreover, peripheral-blood mononuclear cells carrying rs3888188 GG genotype showed a reduced IFITM3 mRNA level compared to cells carrying TT or GT genotype. In conclusion, rs3888188, a functional promoter polymorphism of IFITM3, was identified to influence the risk for pediatric TB in Han Chinese population.",2013 Jul 9,"['Shen, Chen', 'Wu, Xi-rong', 'Jiao, Wei-wei', 'Sun, Lin', 'Feng, Wei-xing', 'Xiao, Jing', 'Miao, Qing', 'Liu, Fang', 'Yin, Qing-qin', 'Zhang, Chen-guang', 'Guo, Ya-jie', 'Shen, A-dong']",PLoS One,,,True
b6682adfe5026c78e3d59b165126abfa8945eb5f,PMC,Dendritic Cell Immunoreceptor Is a New Target for Anti-AIDS Drug Development: Identification of DCIR/HIV-1 Inhibitors,http://dx.doi.org/10.1371/journal.pone.0067873,PMC3706466,23874461,CC BY,"The HIV-1 pandemic continues to expand while no effective vaccine or cure is yet available. Existing therapies have managed to limit mortality and control viral proliferation, but are associated with side effects, do not cure the disease and are subject to development of resistance. Finding new therapeutic targets and drugs is therefore crucial. We have previously shown that the dendritic cell immunoreceptor (DCIR), a C-type lectin receptor expressed on dendritic cells (DCs), acts as an attachment factor for HIV-1 to DCs and contributes to HIV-1 transmission to CD4(+) T lymphocytes (CD4TL). Directly involved in HIV-1 infection, DCIR is expressed in apoptotic or infected CD4TL and promotes trans-infection to bystander cells. Here we report the 3D modelling of the extracellular domain of DCIR. Based on this structure, two surface accessible pockets containing the carbohydrate recognition domain and the EPS binding motif, respectively, were targeted for screening of chemicals that will disrupt normal interaction with HIV-1 particle. Preliminary screening using Raji-CD4-DCIR cells allowed identification of two inhibitors that decreased HIV-1 attachment and propagation. The impact of these inhibitors on infection of DCs and CD4TL was evaluated as well. The results of this study thus identify novel molecules capable of blocking HIV-1 transmission by DCs and CD4TL.",2013 Jul 9,"['Lambert, Alexandra A.', 'Azzi, Arezki', 'Lin, Sheng-Xiang', 'Allaire, Geneviève', 'St-Gelais, Karianne P.', 'Tremblay, Michel J.', 'Gilbert, Caroline']",PLoS One,,,True
19d93173c328e9ca42bd4238ccb39aa8da818422,PMC,An exploration of social and economic outcome and associated health-related quality of life after critical illness in general intensive care unit survivors: a 12-month follow-up study,http://dx.doi.org/10.1186/cc12745,PMC3706775,23714692,CC BY,"INTRODUCTION: The socio-economic impact of critical illnesses on patients and their families in Europe has yet to be determined. The aim of this exploratory study was to estimate changes in family circumstances, social and economic stability, care requirements and access to health services for patients during their first 12 months after ICU discharge. METHODS: Multi-center questionnaire-based study of survivors of critical illness at 6 and 12 months after ICU discharge. RESULTS: Data for 293 consenting patients who spent greater than 48 hours in one of 22 UK ICUs were obtained at 6 and 12 months post-ICU discharge. There was little evidence of a change in accommodation or relationship status between pre-admission and 12 months following discharge from an ICU. A negative impact on family income was reported by 33% of all patients at 6 months and 28% at 12 months. There was nearly a 50% reduction in the number of patients who reported employment as their sole source of income at 12 months (19% to 11%) compared with pre-admission. One quarter of patients reported themselves in need of care assistance at 6 months and 22% at 12 months. The majority of care was provided by family members (80% and 78%, respectively), for half of whom there was a negative impact on employment. Amongst all patients receiving care, 26% reported requiring greater than 50 hours a week. Following discharge, 79% of patients reported attending their primary care physician and 44% had seen a community nurse. Mobility problems nearly doubled between pre-admission and 6 months (32% to 64%). Furthermore, 73% reported moderate or severe pain at 12 months and 44% remained significantly anxious or depressed. CONCLUSIONS: Survivors of critical illness in the UK face a negative impact on employment and commonly have a care requirement after discharge from hospital. This has a corresponding negative impact on family income. The majority of the care required is provided by family members. This effect was apparent by 6 months and had not materially improved by 12 months. This exploratory study has identified the potential for a significant socio-economic burden following critical illness.",2013 May 28,"['Griffiths, John', 'Hatch, Robert A', 'Bishop, Judith', 'Morgan, Kayleigh', 'Jenkinson, Crispin', 'Cuthbertson, Brian H', 'Brett, Stephen J']",Crit Care,,,True
2f9d66c86c6ef08d8e3679e2cd01c2b140e68a32,PMC,A Dual-Mode Surface Display System for the Maturation and Production of Monoclonal Antibodies in Glyco-Engineered Pichia pastoris,http://dx.doi.org/10.1371/journal.pone.0070190,PMC3707868,23875020,CC BY,"State-of-the-art monoclonal antibody (mAb) discovery methods that utilize surface display techniques in prokaryotic and eukaryotic cells require multiple steps of reformatting and switching of hosts to transition from display to expression. This results in a separation between antibody affinity maturation and full-length mAb production platforms. Here, we report for the first time, a method in Glyco-engineered Pichia pastoris that enables simultaneous surface display and secretion of full-length mAb molecules with human-like N-glycans using the same yeast cell. This paradigm takes advantage of homo-dimerization of the Fc portion of an IgG molecule to a surface-anchored ""bait"" Fc, which results in targeting functional “half” IgGs to the cell wall of Pichia pastoris without interfering with the secretion of full length mAb. We show the utility of this method in isolating high affinity, well-expressed anti-PCSK9 leads from a designed library that was created by mating yeasts containing either light chain or heavy chain IgG libraries. Coupled with Glyco-engineered Pichia pastoris , this method provides a powerful tool for the discovery and production of therapeutic human mAbs in the same host thus improving drug developability and potentially shortening the discovery time cycle.",2013 Jul 10,"['Shaheen, Hussam H.', 'Prinz, Bianka', 'Chen, Ming-Tang', 'Pavoor, Tej', 'Lin, Song', 'Houston-Cummings, Nga Rewa', 'Moore, Renee', 'Stadheim, Terrance A.', 'Zha, Dongxing']",PLoS One,,,True
8a2b2c72af5a57c21d912a3f1e543bcd75345883,PMC,Application of next-generation sequencing technologies in virology,http://dx.doi.org/10.1099/vir.0.043182-0,PMC3709572,22647373,CC BY,"The progress of science is punctuated by the advent of revolutionary technologies that provide new ways and scales to formulate scientific questions and advance knowledge. Following on from electron microscopy, cell culture and PCR, next-generation sequencing is one of these methodologies that is now changing the way that we understand viruses, particularly in the areas of genome sequencing, evolution, ecology, discovery and transcriptomics. Possibilities for these methodologies are only limited by our scientific imagination and, to some extent, by their cost, which has restricted their use to relatively small numbers of samples. Challenges remain, including the storage and analysis of the large amounts of data generated. As the chemistries employed mature, costs will decrease. In addition, improved methods for analysis will become available, opening yet further applications in virology including routine diagnostic work on individuals, and new understanding of the interaction between viral and host transcriptomes. An exciting era of viral exploration has begun, and will set us new challenges to understand the role of newly discovered viral diversity in both disease and health.",2012 Sep,"['Radford, Alan D.', 'Chapman, David', 'Dixon, Linda', 'Chantrey, Julian', 'Darby, Alistair C.', 'Hall, Neil']",J Gen Virol,,,True
d4c0c411fdb8d2389288d0389cf02121ae6d8a9c,PMC,"Comprehensive analysis of the HEPN superfamily: identification of novel roles in intra-genomic conflicts, defense, pathogenesis and RNA processing",http://dx.doi.org/10.1186/1745-6150-8-15,PMC3710099,23768067,CC BY,"BACKGROUND: The major role of enzymatic toxins that target nucleic acids in biological conflicts at all levels has become increasingly apparent thanks in large part to the advances of comparative genomics. Typically, toxins evolve rapidly hampering the identification of these proteins by sequence analysis. Here we analyze an unexpectedly widespread superfamily of toxin domains most of which possess RNase activity. RESULTS: The HEPN superfamily is comprised of all α-helical domains that were first identified as being associated with DNA polymerase β-type nucleotidyltransferases in prokaryotes and animal Sacsin proteins. Using sensitive sequence and structure comparison methods, we vastly extend the HEPN superfamily by identifying numerous novel families and by detecting diverged HEPN domains in several known protein families. The new HEPN families include the RNase LS and LsoA catalytic domains, KEN domains (e.g. RNaseL and Ire1) and the RNase domains of RloC and PrrC. The majority of HEPN domains contain conserved motifs that constitute a metal-independent endoRNase active site. Some HEPN domains lacking this motif probably function as non-catalytic RNA-binding domains, such as in the case of the mannitol repressor MtlR. Our analysis shows that HEPN domains function as toxins that are shared by numerous systems implicated in intra-genomic, inter-genomic and intra-organismal conflicts across the three domains of cellular life. In prokaryotes HEPN domains are essential components of numerous toxin-antitoxin (TA) and abortive infection (Abi) systems and in addition are tightly associated with many restriction-modification (R-M) and CRISPR-Cas systems, and occasionally with other defense systems such as Pgl and Ter. We present evidence of multiple modes of action of HEPN domains in these systems, which include direct attack on viral RNAs (e.g. LsoA and RNase LS) in conjunction with other RNase domains (e.g. a novel RNase H fold domain, NamA), suicidal or dormancy-inducing attack on self RNAs (RM systems and possibly CRISPR-Cas systems), and suicidal attack coupled with direct interaction with phage components (Abi systems). These findings are compatible with the hypothesis on coupling of pathogen-targeting (immunity) and self-directed (programmed cell death and dormancy induction) responses in the evolution of robust antiviral strategies. We propose that altruistic cell suicide mediated by HEPN domains and other functionally similar RNases was essential for the evolution of kin and group selection and cell cooperation. HEPN domains were repeatedly acquired by eukaryotes and incorporated into several core functions such as endonucleolytic processing of the 5.8S-25S/28S rRNA precursor (Las1), a novel ER membrane-associated RNA degradation system (C6orf70), sensing of unprocessed transcripts at the nuclear periphery (Swt1). Multiple lines of evidence suggest that, similar to prokaryotes, HEPN proteins were recruited to antiviral, antitransposon, apoptotic systems or RNA-level response to unfolded proteins (Sacsin and KEN domains) in several groups of eukaryotes. CONCLUSIONS: Extensive sequence and structure comparisons reveal unexpectedly broad presence of the HEPN domain in an enormous variety of defense and stress response systems across the tree of life. In addition, HEPN domains have been recruited to perform essential functions, in particular in eukaryotic rRNA processing. These findings are expected to stimulate experiments that could shed light on diverse cellular processes across the three domains of life. REVIEWERS: This article was reviewed by Martijn Huynen, Igor Zhulin and Nick Grishin",2013 Jun 15,"['Anantharaman, Vivek', 'Makarova, Kira S', 'Burroughs, A Maxwell', 'Koonin, Eugene V', 'Aravind, L']",Biol Direct,,,True
c98f64c50d8a1c2d378db2e8da009c2dbc7936b1,PMC,Schistosomiasis control and the health system in P.R. China,http://dx.doi.org/10.1186/2049-9957-1-8,PMC3710143,23849320,CC BY,"Over the last sixty years advances have been made in the control of schistosomiasis in P.R. China. There are, however, difficult challenges still to be met. This paper looks at the extent to which the health system offers a positive environment for the control of the disease. It starts by tracing three phases in schistosomiasis control: disease elimination strategy through snail control (1950s-early 1980s); morbidity control strategy based on chemotherapy (mid 1980s to 2003); integrated control strategy (2004+). Each one of these phases took place in distinct policy-making environments. The paper partly draws on these phases to set out five issues of disease control and discusses them in the context of the health system and its recent trends. These cover the policy-making process, intersectoral action for health, equity and access to health services, funding for public goods and externalities, and strengthening resource management and planning. These issues form the basis of an agenda for integrating research and capacity strengthening in the Chinese health system with a view to creating a more positive enabling environment for schistosomiasis control. In so doing it is important to emphasize the role and integrity of the public sector against its commercialization, the underlying value of equity, a systems wide perspective, and the role of advocacy.",2012 Nov 1,"['Collins, Charles', 'Xu, Jing', 'Tang, Shenglan']",Infect Dis Poverty,,,True
cfb5101deb971a2922f94946edee44ebe7a7ac97,PMC,Schistosomiasis control and the health system in P.R. China,http://dx.doi.org/10.1186/2049-9957-1-8,PMC3710143,23849320,CC BY,"Over the last sixty years advances have been made in the control of schistosomiasis in P.R. China. There are, however, difficult challenges still to be met. This paper looks at the extent to which the health system offers a positive environment for the control of the disease. It starts by tracing three phases in schistosomiasis control: disease elimination strategy through snail control (1950s-early 1980s); morbidity control strategy based on chemotherapy (mid 1980s to 2003); integrated control strategy (2004+). Each one of these phases took place in distinct policy-making environments. The paper partly draws on these phases to set out five issues of disease control and discusses them in the context of the health system and its recent trends. These cover the policy-making process, intersectoral action for health, equity and access to health services, funding for public goods and externalities, and strengthening resource management and planning. These issues form the basis of an agenda for integrating research and capacity strengthening in the Chinese health system with a view to creating a more positive enabling environment for schistosomiasis control. In so doing it is important to emphasize the role and integrity of the public sector against its commercialization, the underlying value of equity, a systems wide perspective, and the role of advocacy.",2012 Nov 1,"['Collins, Charles', 'Xu, Jing', 'Tang, Shenglan']",Infect Dis Poverty,,,False
4209267ef4da6a8206733929e58967faebf8a5b7,PMC,Infectious disease emergence and global change: thinking systemically in a shrinking world,http://dx.doi.org/10.1186/2049-9957-1-5,PMC3710192,23849217,CC BY,"BACKGROUND: Concern intensifying that emerging infectious diseases and global environmental changes that could generate major future human pandemics. METHOD: A focused literature review was undertaken, partly informed by a forthcoming report on environment, agriculture and infectious diseases of poverty, facilitated by the Special Programme for Tropical Diseases. RESULTS: More than ten categories of infectious disease emergence exist, but none formally analyse past, current or future burden of disease. Other evidence suggests that the dominant public health concern focuses on two informal groupings. Most important is the perceived threat of newly recognised infections, especially viruses that arise or are newly discovered in developing countries that originate in species exotic to developed countries, such as non-human primates, bats and rodents. These pathogens may be transmitted by insects or bats, or via direct human contact with bushmeat. The second group is new strains of influenza arising from intensively farmed chickens or pigs, or emerging from Asian “wet markets” where several bird species have close contact. Both forms appear justified because of two great pandemics: HIV/AIDS (which appears to have originated from bushmeat hunting in Africa before emerging globally) and Spanish influenza, which killed up to 2.5% of the human population around the end of World War I. Insufficiently appreciated is the contribution of the milieu which appeared to facilitate the high disease burden in these pandemics. Additionally, excess anxiety over emerging infectious diseases diverts attention from issues of greater public health importance, especially: (i) existing (including neglected) infectious diseases and (ii) the changing milieu that is eroding the determinants of immunity and public health, caused by adverse global environmental changes, including climate change and other components of stressed life and civilisation-supporting systems. CONCLUSIONS: The focus on novel pathogens and minor forms of anti-microbial resistance in emerging disease literature is unjustified by their burden of disease, actual and potential, and diverts attention from far more important health problems and determinants. There is insufficient understanding of systemic factors that promote pandemics. Adverse global change could generate circumstances conducive to future pandemics with a high burden of disease, arising via anti-microbial and insecticidal resistance, under-nutrition, conflict, and public health breakdown.",2012 Oct 25,"Butler, Colin D",Infect Dis Poverty,,,True
6b659b911dd8957f6bda11eb20381946e3910564,PMC,Infectious disease emergence and global change: thinking systemically in a shrinking world,http://dx.doi.org/10.1186/2049-9957-1-5,PMC3710192,23849217,CC BY,"BACKGROUND: Concern intensifying that emerging infectious diseases and global environmental changes that could generate major future human pandemics. METHOD: A focused literature review was undertaken, partly informed by a forthcoming report on environment, agriculture and infectious diseases of poverty, facilitated by the Special Programme for Tropical Diseases. RESULTS: More than ten categories of infectious disease emergence exist, but none formally analyse past, current or future burden of disease. Other evidence suggests that the dominant public health concern focuses on two informal groupings. Most important is the perceived threat of newly recognised infections, especially viruses that arise or are newly discovered in developing countries that originate in species exotic to developed countries, such as non-human primates, bats and rodents. These pathogens may be transmitted by insects or bats, or via direct human contact with bushmeat. The second group is new strains of influenza arising from intensively farmed chickens or pigs, or emerging from Asian “wet markets” where several bird species have close contact. Both forms appear justified because of two great pandemics: HIV/AIDS (which appears to have originated from bushmeat hunting in Africa before emerging globally) and Spanish influenza, which killed up to 2.5% of the human population around the end of World War I. Insufficiently appreciated is the contribution of the milieu which appeared to facilitate the high disease burden in these pandemics. Additionally, excess anxiety over emerging infectious diseases diverts attention from issues of greater public health importance, especially: (i) existing (including neglected) infectious diseases and (ii) the changing milieu that is eroding the determinants of immunity and public health, caused by adverse global environmental changes, including climate change and other components of stressed life and civilisation-supporting systems. CONCLUSIONS: The focus on novel pathogens and minor forms of anti-microbial resistance in emerging disease literature is unjustified by their burden of disease, actual and potential, and diverts attention from far more important health problems and determinants. There is insufficient understanding of systemic factors that promote pandemics. Adverse global change could generate circumstances conducive to future pandemics with a high burden of disease, arising via anti-microbial and insecticidal resistance, under-nutrition, conflict, and public health breakdown.",2012 Oct 25,"Butler, Colin D",Infect Dis Poverty,,,False
5076cec908e9bc3ba685507e00ac19deab50b02e,PMC,Peptide-Based Vaccinology: Experimental and Computational Approaches to Target Hypervariable Viruses through the Fine Characterization of Protective Epitopes Recognized by Monoclonal Antibodies and the Identification of T-Cell-Activating Peptides,http://dx.doi.org/10.1155/2013/521231,PMC3710646,23878584,CC BY,"Defining immunogenic domains of viral proteins capable of eliciting a protective immune response is crucial in the development of novel epitope-based prophylactic strategies. This is particularly important for the selective targeting of conserved regions shared among hypervariable viruses. Studying postinfection and postimmunization sera, as well as cloning and characterization of monoclonal antibodies (mAbs), still represents the best approach to identify protective epitopes. In particular, a protective mAb directed against conserved regions can play a key role in immunogen design and in human therapy as well. Experimental approaches aiming to characterize protective mAb epitopes or to identify T-cell-activating peptides are often burdened by technical limitations and can require long time to be correctly addressed. Thus, in the last decade many epitope predictive algorithms have been developed. These algorithms are continually evolving, and their use to address the empirical research is widely increasing. Here, we review several strategies based on experimental techniques alone or addressed by in silico analysis that are frequently used to predict immunogens to be included in novel epitope-based vaccine approaches. We will list the main strategies aiming to design a new vaccine preparation conferring the protection of a neutralizing mAb combined with an effective cell-mediated response.",2013 Jun 26,"['Castelli, Matteo', 'Cappelletti, Francesca', 'Diotti, Roberta Antonia', 'Sautto, Giuseppe', 'Criscuolo, Elena', 'Dal Peraro, Matteo', 'Clementi, Nicola']",Clin Dev Immunol,,,True
3daf73ca2c2bb003b6f6201b1924660cc2fd75a2,PMC,Suppression of Coronavirus Replication by Cyclophilin Inhibitors,http://dx.doi.org/10.3390/v5051250,PMC3712306,23698397,CC BY,"Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS), feline infectious peritonitis (FIP), mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA), could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.",2013 May 22,"['Tanaka, Yoshikazu', 'Sato, Yuka', 'Sasaki, Takashi']",Viruses,,,True
6129997a5fe45179b0acf89be52fe803bf5719dc,PMC,Microbial Translocation Contribute to Febrile Episodes in Adults with Chemotherapy-Induced Neutropenia,http://dx.doi.org/10.1371/journal.pone.0068056,PMC3712968,23874493,CC BY,"In this study we sought to determine the contribution of microbial translocation to febrile episodes with no attributable microbiological cause (Fever of Unknown Origin, FUO) in an adult febrile neutropaenic cohort. Endotoxin concentrations were measured with the chromogenic Limulus Amoebocyte Assay and used as a direct measure of bacterial products whilst soluble CD14 (sCD14), measured with ELISA was selected as an indicator of the early host response to endotoxins. Endotoxin concentrations in this cohort were generally elevated but did not differ with the presentation of fever. Further stratification of the febrile episodes based on the microbiological findings revealed significantly (p = 0.0077) elevated endotoxin concentrations in FUO episodes compared with episodes with documented bacterial and viral findings. sCD14 concentrations were however, elevated in febrile episodes (p = 0.0066) and no association was observed between sCD14 concentration and microbiological findings. However, FUO episodes and episodes with Gram-negative bacteraemia were associated with higher median sCD14 concentrations than episodes with Gram-positive bacteraemia (p = 0.030). In conclusion, our findings suggest that in the absence of microbiological findings, microbial translocation could contribute to febrile episodes in an adult neutropaenic cohort. We further observed an association between prophylactic antibiotic use and increased plasma endotoxin concentrations (p = 0.0212).",2013 Jul 16,"['Wong, Michelle', 'Barqasho, Babilonia', 'Öhrmalm, Lars', 'Tolfvenstam, Thomas', 'Nowak, Piotr']",PLoS One,,,True
374d22c2f8bc21e4e0525c7486d131db2cf607f4,PMC,Major Infection Events Over 5 Years: How Is Media Coverage Influencing Online Information Needs of Health Care Professionals and the Public?,http://dx.doi.org/10.2196/jmir.2146,PMC3713905,23856364,CC BY,"BACKGROUND: The last decade witnessed turbulent events in public health. Emerging infections, increase of antimicrobial resistance, deliberately released threats and ongoing battles with common illnesses were amplified by the spread of disease through increased international travel. The Internet has dramatically changed the availability of information about outbreaks; however, little research has been done in comparing the online behavior of public and professionals around the same events and the effect of media coverage of outbreaks on information needs. OBJECTIVE: To investigate professional and public online information needs around major infection outbreaks and correlate these with media coverage. Questions include (1) How do health care professionals’ online needs for public health and infection control information differ from those of the public?, (2) Does dramatic media coverage of outbreaks contribute to the information needs among the public?, and (3) How do incidents of diseases and major policy events relate to the information needs of professionals? METHODS: We used three longitudinal time-based datasets from mid-2006 until end of 2010: (1) a unique record of professional online behavior on UK infection portals: National electronic Library of Infection and National Resource of Infection Control (NeLI/NRIC), (2) equivalent public online information needs (Google Trends), and (3) relevant media coverage (LexisNexis). Analysis of NeLI/NRIC logs identified the highest interest around six major infectious diseases: Clostridium difficile (C difficile)/Methicillin-resistant Staphylococcus aureus (MRSA), tuberculosis, meningitis, norovirus, and influenza. After pre-processing, the datasets were analyzed and triangulated with each other. RESULTS: Public information needs were more static, following the actual disease occurrence less than those of professionals, whose needs increase with public health events (eg, MRSA/C difficile) and the release of major national policies or important documents. Media coverage of events resulted in major public interest (eg, the 2007/2008 UK outbreak of C difficile/MRSA). An exception was norovirus, showing a seasonal pattern for both public and professionals, which matched the periodic disease occurrence. Meningitis was a clear example of a disease with heightened media coverage tending to focus on individual and celebrity cases. Influenza was a major concern during the 2009 H1N1 outbreak creating massive public interest in line with the spring and autumn peaks in cases; although in autumn 2009, there was no corresponding increase in media coverage. Online resources play an increasing role in fulfilling professionals’ and public information needs. CONCLUSIONS: Significant factors related to a surge of professional interest around a disease were typically key publications and major policy changes. Public interests seem more static and correlate with media influence but to a lesser extent than expected. The only exception was norovirus, exhibiting online public and professional interest correlating with seasonal occurrences of the disease. Public health agencies with responsibility for risk communication of public health events, in particular during outbreaks and emergencies, need to collaborate with media in order to ensure the coverage is high quality and evidence-based, while professionals’ information needs remain mainly fulfilled by online open access to key resources.",2013 Jul 15,"['Kostkova, Patty', 'Fowler, David', 'Wiseman, Sue', 'Weinberg, Julius R']",J Med Internet Res,,,False
d479fdff7406604cebef7b82284ab7a275e17925,PMC,The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses,http://dx.doi.org/10.1371/journal.ppat.1003500,PMC3715407,23874204,CC BY,"The small size of RNA virus genomes (2-to-32 kb) has been attributed to high mutation rates during replication, which is thought to lack proof-reading. This paradigm is being revisited owing to the discovery of a 3′-to-5′ exoribonuclease (ExoN) in nidoviruses, a monophyletic group of positive-stranded RNA viruses with a conserved genome architecture. ExoN, a homolog of canonical DNA proof-reading enzymes, is exclusively encoded by nidoviruses with genomes larger than 20 kb. All other known non-segmented RNA viruses have smaller genomes. Here we use evolutionary analyses to show that the two- to three-fold expansion of the nidovirus genome was accompanied by a large number of replacements in conserved proteins at a scale comparable to that in the Tree of Life. To unravel common evolutionary patterns in such genetically diverse viruses, we established the relation between genomic regions in nidoviruses in a sequence alignment-free manner. We exploited the conservation of the genome architecture to partition each genome into five non-overlapping regions: 5′ untranslated region (UTR), open reading frame (ORF) 1a, ORF1b, 3′ORFs (encompassing the 3′-proximal ORFs), and 3′ UTR. Each region was analyzed for its contribution to genome size change under different models. The non-linear model statistically outperformed the linear one and captured >92% of data variation. Accordingly, nidovirus genomes were concluded to have reached different points on an expansion trajectory dominated by consecutive increases of ORF1b, ORF1a, and 3′ORFs. Our findings indicate a unidirectional hierarchical relation between these genome regions, which are distinguished by their expression mechanism. In contrast, these regions cooperate bi-directionally on a functional level in the virus life cycle, in which they predominantly control genome replication, genome expression, and virus dissemination, respectively. Collectively, our findings suggest that genome architecture and the associated region-specific division of labor leave a footprint on genome expansion and may limit RNA genome size.",2013 Jul 18,"['Lauber, Chris', 'Goeman, Jelle J.', 'Parquet, Maria del Carmen', 'Thi Nga, Phan', 'Snijder, Eric J.', 'Morita, Kouichi', 'Gorbalenya, Alexander E.']",PLoS Pathog,,,True
a2e8d9291e399c6d8adc6d39318de197e86b3f4e,PMC,Antiviral Activity of Glycyrrhizin against Hepatitis C Virus In Vitro,http://dx.doi.org/10.1371/journal.pone.0068992,PMC3715454,23874843,CC BY,"Glycyrrhizin (GL) has been used in Japan to treat patients with chronic viral hepatitis, as an anti-inflammatory drug to reduce serum alanine aminotransferase levels. GL is also known to exhibit various biological activities, including anti-viral effects, but the anti-hepatitis C virus (HCV) effect of GL remains to be clarified. In this study, we demonstrated that GL treatment of HCV-infected Huh7 cells caused a reduction of infectious HCV production using cell culture-produced HCV (HCVcc). To determine the target step in the HCV lifecycle of GL, we used HCV pseudoparticles (HCVpp), replicon, and HCVcc systems. Significant suppressions of viral entry and replication steps were not observed. Interestingly, extracellular infectivity was decreased, and intracellular infectivity was increased. By immunofluorescence and electron microscopic analysis of GL treated cells, HCV core antigens and electron-dense particles had accumulated on endoplasmic reticulum attached to lipid droplet (LD), respectively, which is thought to act as platforms for HCV assembly. Furthermore, the amount of HCV core antigen in LD fraction increased. Taken together, these results suggest that GL inhibits release of infectious HCV particles. GL is known to have an inhibitory effect on phospholipase A2 (PLA2). We found that group 1B PLA2 (PLA2G1B) inhibitor also decreased HCV release, suggesting that suppression of virus release by GL treatment may be due to its inhibitory effect on PLA2G1B. Finally, we demonstrated that combination treatment with GL augmented IFN-induced reduction of virus in the HCVcc system. GL is identified as a novel anti-HCV agent that targets infectious virus particle release.",2013 Jul 18,"['Matsumoto, Yoshihiro', 'Matsuura, Tomokazu', 'Aoyagi, Haruyo', 'Matsuda, Mami', 'Hmwe, Su Su', 'Date, Tomoko', 'Watanabe, Noriyuki', 'Watashi, Koichi', 'Suzuki, Ryosuke', 'Ichinose, Shizuko', 'Wake, Kenjiro', 'Suzuki, Tetsuro', 'Miyamura, Tatsuo', 'Wakita, Takaji', 'Aizaki, Hideki']",PLoS One,,,True
a7e3179a2dbf9f386ac702c0a6fc780889773829,PMC,Lithium chloride promotes host resistance against Pseudomonas aeruginosa keratitis,,PMC3716469,23878501,CC BY,"PURPOSE: To explore the role of lithium chloride (LiCl) in Pseudomonas aeruginosa (PA) keratitis. METHODS: B6 mice were subconjunctivally injected with LiCl in contrast to appropriate control sodium chloride (NaCl), and then routinely infected with PA. Clinical score, slit-lamp photography, hematoxylin and eosin (H&E) staining, and bacterial plate counts were used to determine the role of LiCl in PA keratitis. Messenger ribonucleic acid and protein levels of inflammatory cytokines in PA-challenged mouse corneas and in vitro cultured macrophages and neutrophils were measured with real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Apoptosis of the infiltrating inflammatory cells in the PA-infected murine corneas was assessed using terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling staining and propidium iodide staining associated with flow cytometry. In cultured murine macrophages and neutrophils, cell apoptosis was determined with annexin V/propidium iodide double staining associated with flow cytometry and western blot analysis for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase. RESULTS: Treatment with LiCl reduced the severity of corneal disease by reducing corneal inflammatory response and bacterial burden. Moreover, LiCl increased anti-inflammatory cytokine interleukin-10 levels, decreased proinflammatory cytokine tumor necrosis factor-α levels, and enhanced apoptosis of infiltrating macrophages and neutrophils in the PA-infected mouse corneas. In vitro studies further confirmed that LiCl elevated anti-inflammatory cytokine expression but reduced proinflammatory cytokine production, as well as promoted cell apoptosis in murine macrophages and neutrophils. CONCLUSIONS: This study demonstrates a protective role of LiCl in PA keratitis. LiCl promotes host resistance against PA infection by suppressing inflammatory responses, enhancing inflammatory cell apoptosis, and promoting bacterial clearance.",2013 Jul 19,"['Chen, Kang', 'Wu, Yongjian', 'Zhu, Min', 'Deng, Qiuchan', 'Nie, Xinxin', 'Li, Meiyu', 'Wu, Minhao', 'Huang, Xi']",Mol Vis,,,True
e4387a9c18bca710c7fdc986a6b2f8df671e29b8,PMC,"Isolation and genetic characterization of human coronavirus NL63 in primary human renal proximal tubular epithelial cells obtained from a commercial supplier, and confirmation of its replication in two different types of human primary kidney cells",http://dx.doi.org/10.1186/1743-422X-10-213,PMC3716658,23805916,CC BY,"BACKGROUND: Cryopreserved primary human renal proximal tubule epithelial cells (RPTEC) were obtained from a commercial supplier for studies of Simian virus 40 (SV40). Within twelve hrs after cell cultures were initiated, cytoplasmic vacuoles appeared in many of the RPTEC. The RPTEC henceforth deteriorated rapidly. Since SV40 induces the formation of cytoplasmic vacuoles, this batch of RPTEC was rejected for the SV40 study. Nevertheless, we sought the likely cause(s) of the deterioration of the RPTEC as part of our technology development efforts. METHODS: Adventitious viruses in the RPTEC were isolated and/or detected and identified by isolation in various indicator cell lines, observation of cytopathology, an immunoflurorescence assay, electron microscopy, PCR, and sequencing. RESULTS: Cytomegalovirus (CMV) was detected in some RPTEC by cytology, an immunofluorescence assay, and PCR. Human Herpesvirus 6B was detected by PCR of DNA extracted from the RPTEC, but was not isolated. Human coronavirus NL63 was isolated and identified by RT-PCR and sequencing, and its replication in a fresh batch of RPTEC and another type of primary human kidney cells was confirmed. CONCLUSIONS: At least 3 different adventitious viruses were present in the batch of contaminated RPTEC. Whereas we are unable to determine whether the original RPTEC were pre-infected prior to their separation from other kidney cells, or had gotten contaminated with HCoV-NL63 from an ill laboratory worker during their preparation for commercial sale, our findings are a reminder that human-derived biologicals should always be considered as potential sources of infectious agents. Importantly, HCoV-NL63 replicates to high titers in some primary human kidney cells.",2013 Jun 27,"['Lednicky, John A', 'Waltzek, Thomas B', 'McGeehan, Elizabeth', 'Loeb, Julia C', 'Hamilton, Sara B', 'Luetke, Maya C']",Virol J,,,True
40540b92cbf5d985e0648733de6f4a9062e1bbcf,PMC,Genetic characterization of EV71 isolates from 2004 to 2010 reveals predominance and persistent circulation of the newly proposed genotype D and recent emergence of a distinct lineage of subgenotype C2 in Hong Kong,http://dx.doi.org/10.1186/1743-422X-10-222,PMC3716818,23822185,CC BY,"BACKGROUND: Enterovirus 71 (EV71) is a common etiological agent of hand, foot and mouth disease (HFMD) in children. EV71 epidemics have been reported in Hong Kong in recent years, and yet the genetic information of EV71 strains circulating in our locality is limited. The objective of this study was to investigate the genetic evolution of these EV71 isolates in Hong Kong over a 7-year period. METHODS: Twenty-two EV71 isolates from Hong Kong during 2004–2010 were included for phylogenetic analysis using partial VP2-VP3, 2C and 3D regions. Eight EV71 strains were selected for complete genome sequencing and recombination analysis. RESULTS: Among the 22 EV71 isolates, 20 belonged to subgenotype C4 and 2 belonged to subgenotype C2 based on the phylogenetic analysis of partial VP2-VP3, 2C and 3D gene regions. Phylogenetic, similarity plot and bootscan analyses using complete genome sequences of seven EV71 isolates of subgenotype C4 supported that the “double-recombinant” strains of subgenotype C4 persistently circulating in Hong Kong should belong to a newly proposed genotype D. Further analysis revealed two clusters, subgenotypes C4b and C4a (proposed genotypes D1a and D1b respectively), with “genotype D1b” strains being predominant in recent years in Hong Kong. A distinct lineage of EV71 subgenotype C2 has emerged in Hong Kong in 2008. The evolutionary rate of EV71 was 3.1 × 10(-3) nucleotide substitutions per site per year similar to that of other enterovirus, such as EV68, but was relatively lower than those of echovirus 30 and poliovirus. Molecular clock analysis using VP1 gene dated the time to the most recent common ancestor of all EV71 genotypes to 1900s, while the EV71 “double-recombinant” strains of “genotype D” were detected as early as 1998. CONCLUSIONS: This study provides the molecular basis for proposing a new “genotype D” of EV71 and assigning a discrete lineage of subgenotype C2. EV71 strains of “genotype D” have been circulating in Hong Kong for over 7 years, with “genotype D1b” being predominant.",2013 Jul 4,"['Yip, Cyril CY', 'Lau, Susanna KP', 'Lo, Janice YC', 'Chan, Kwok-Hung', 'Woo, Patrick CY', 'Yuen, Kwok-Yung']",Virol J,,,True
59cd9fecfcd1ef7eb2bbe427809ef0fd01e894b5,PMC,Maintaining the structural integrity of the bamboo mosaic virus 3′ untranslated region is necessary for retaining the catalytic constant for minus-strand RNA synthesis,http://dx.doi.org/10.1186/1743-422X-10-208,PMC3720222,23800142,CC BY,"BACKGROUND: Bamboo mosaic virus (BaMV) and the Potato virus X (PVX) are members of the genus Potexvirus and have a single-stranded positive-sense RNA genome. The 3′-untranslated region (UTR) of the BaMV RNA genome was mapped structurally into ABC (a cloverleaf-like), D (a stem-loop), and E (pseudoknot) domains. The BaMV replicase complex that was isolated from the infected plants was able to recognize the 3′ UTR of PVX RNA to initiate minus-strand RNA synthesis in vitro. RESULTS: To investigate whether the 3′ UTR of PVX RNA is also compatible with BaMV replicase in vivo, we constructed chimera mutants using a BaMV backbone containing the PVX 3′ UTR, which was inserted in or used to replace the various domains in the 3′ UTR of BaMV. None of the mutants, except for the mutant with the PVX 3′ UTR inserted upstream of the BaMV 3′ UTR, exhibited a detectable accumulation of viral RNA in Nicotiana benthamiana plants. The in vitro BaMV RdRp replication assay demonstrated that the RNA products were generated by the short RNA transcripts, which were derived from the chimera mutants to various extents. Furthermore, the V(max)/K(M) of the BaMV 3′ UTR (rABCDE) was approximately three fold higher than rABCP, rP, and rDE in minus-strand RNA synthesis. These mutants failed to accumulate viral products in protoplasts and plants, but were adequately replicated in vitro. CONCLUSIONS: Among the various studied BaMV/PVX chimera mutants, the BaMV-S/PABCDE that contained non-interrupted BaMV 3′ UTR was the only mutant that exhibited a wild-type level of viral product accumulation in protoplasts and plants. These results indicate that the continuity of the domains in the 3′ UTR of BaMV RNA was not interrupted and the domains were not replaced with the 3′ UTR of PVX RNA in vivo.",2013 Jun 24,"['Chen, I-Hsuan', 'Chu, Chiu-Heiu', 'Lin, Jen-Wen', 'Hsu, Yau-Heiu', 'Tsai, Ching-Hsiu']",Virol J,,,True
520074edb06a53db798395f49940fb5d24417b62,PMC,Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 4 Induces Apoptosis Dependent on Its 3C-Like Serine Protease Activity,http://dx.doi.org/10.1371/journal.pone.0069387,PMC3720278,23936003,CC BY,"Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease in pigs caused by PRRS virus (PRRSV). Although PRRSV infection-induced cell apoptosis has been established, the related viral protein is still unknown. Here, we reported that PRRSV nonstructural protein 4 (nsp4) was a critical apoptosis inducer. Nsp4 could activate caspase-3, -8, and -9. Using truncated constructs without different domains in nsp4, we demonstrated that the full-length of nsp4 structure was required for its apoptosis-inducing activity. Furthermore, using site-directed mutagenesis to inactivate the 3C-like serine protease activity of nsp4, we showed that nsp4-induced apoptosis was dependent on its serine protease activity. The ability of nsp4 to induce apoptosis was significantly impaired by His39, Asp64, and Ser118 mutations, suggesting that His39, Asp64, and Ser118 were essential for nsp4 to trigger apoptosis. In conclusion, our present work showed that PRRSV nsp4 could induce apoptosis in host cells and might be partially responsible for the apoptosis induced by PRRSV infection. PRRSV 3C-like protease-mediated apoptosis represents the first report in the genus Arterivirus, family Arteriviridae.",2013 Jul 23,"['Ma, Zhitao', 'Wang, Yalan', 'Zhao, Haiyan', 'Xu, Ao-Tian', 'Wang, Yongqiang', 'Tang, Jun', 'Feng, Wen-hai']",PLoS One,,,True
e9c899d06f0e31a0d2c58cd4d82edb0086f9ed04,PMC,An outbreak of feline infectious peritonitis in a Taiwanese shelter: epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus,http://dx.doi.org/10.1186/1297-9716-44-57,PMC3720556,23865689,CC BY,"Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV) infection. FCoV can be divided into serotypes I and II. The virus that causes FIP (FIPV) is believed to occur sporadically and spread infrequently from cat to cat. Recently, an FIP outbreak from an animal shelter was confirmed in Taiwan. FCoV from all the cats in this shelter were analyzed to determine the epidemiology of this outbreak. Thirteen of 46 (28.2%) cats with typical signs of FIP were identified. Among them, seven cats were confirmed by necropsy and/or histopathological examinations. Despite the fact that more than one FCoV was identified in this multi-cat environment, the eight FIP cats were invariably found to be infected with a type II FCoV. Sequence analysis revealed that the type II FIPV detected from fecal samples, body effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene. Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene. Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death. Taken together, our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment.",2013 Jul 17,"['Wang, Ying-Ting', 'Su, Bi-Ling', 'Hsieh, Li-En', 'Chueh, Ling-Ling']",Vet Res,,,True
10fbf7274b0bdfe7153269489851fc3d8f121bcd,PMC,Characterization of Rotavirus RNAs That Activate Innate Immune Signaling through the RIG-I-Like Receptors,http://dx.doi.org/10.1371/journal.pone.0069825,PMC3720929,23894547,CC BY,"In mammalian cells, the first line of defense against viral pathogens is the innate immune response, which is characterized by induction of type I interferons (IFN) and other pro-inflammatory cytokines that establish an antiviral milieu both in infected cells and in neighboring uninfected cells. Rotavirus, a double-stranded RNA virus of the Reoviridae family, is the primary etiological agent of severe diarrhea in young children worldwide. Previous studies demonstrated that rotavirus replication induces a MAVS-dependent type I IFN response that involves both RIG-I and MDA5, two cytoplasmic viral RNA sensors. This study reports the isolation and characterization of rotavirus RNAs that activate IFN signaling. Using an in vitro approach with purified rotavirus double-layer particles, nascent single-stranded RNA (ssRNA) transcripts (termed in vitro ssRNA) were found to be potent IFN inducers. In addition, large RNAs isolated from rotavirus-infected cells six hours post-infection (termed in vivo 6 hr large RNAs), also activated IFN signaling, whereas a comparable large RNA fraction isolated from cells infected for only one hour lacked this stimulatory activity. Experiments using knockout murine embryonic fibroblasts showed that RIG-I is required for and MDA5 partly contributes to innate immune signaling by both in vitro ssRNA and in vivo 6 hr large RNAs. Enzymatic studies demonstrated that in vitro ssRNA and in vivo 6 hr large RNA samples contain uncapped RNAs with exposed 5’ phosphate groups. RNAs lacking 2’-O-methylated 5’ cap structures were also detected in the in vivo 6 hr large RNA sample. Taken together, our data provide strong evidence that the rotavirus VP3 enzyme, which encodes both guanylyltransferase and methyltransferase activities, is not completely efficient at either 5’ capping or 2’-O-methylation of the 5’ cap structures of viral transcripts, and in this way produces RNA patterns that activate innate immune signaling through the RIG-I-like receptors.",2013 Jul 23,"['Uzri, Dina', 'Greenberg, Harry B.']",PLoS One,,,True
b59b58c13370a390a58c6cd79e61f97bf9bee37d,PMC,Development of an Aerosol Model of Cryptococcus Reveals Humidity as an Important Factor Affecting the Viability of Cryptococcus during Aerosolization,http://dx.doi.org/10.1371/journal.pone.0069804,PMC3720958,23894542,CC BY,"Cryptococcus is an emerging global health threat that is annually responsible for over 1,000,000 infections and one third of all AIDS patient deaths. There is an ongoing outbreak of cryptococcosis in the western United States and Canada. Cryptococcosis is a disease resulting from the inhalation of the infectious propagules from the environment. The current and most frequently used animal infection models initiate infection via liquid suspension through intranasal instillation or intravenous injection. These models do not replicate the typically dry nature of aerosol exposure and may hinder our ability to decipher the initial events that lead to clearance or the establishment of infection. We have established a standardized aerosol model of murine infection for the human fungal pathogen Cryptococcus. Aerosolized cells were generated utilizing a Collison nebulizer in a whole-body Madison Chamber at different humidity conditions. The aerosols inside the chamber were sampled using a BioSampler to determine viable aerosol concentration and spray factor (ratio of viable aerosol concentration to total inoculum concentration). We have effectively delivered yeast and yeast-spore mixtures to the lungs of mice and observed the establishment of disease. We observed that growth conditions prior to exposure and humidity within the Madison Chamber during exposure can alter Cryptococcus survival and dose retained in mice.",2013 Jul 23,"['Springer, Deborah J.', 'Saini, Divey', 'Byrnes, Edmond J.', 'Heitman, Joseph', 'Frothingham, Richard']",PLoS One,,,True
61573a5ebe4f84a5b5738bc12a3c18d2bf69651c,PMC,The Role of FGL2 in the Pathogenesis and Treatment of Hepatitis C Virus Infection,http://dx.doi.org/10.5041/RMMJ.10004,PMC3721661,23908776,CC BY,"Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide and remains the most common indication for liver transplantation. The current standard of care leads to a sustained viral response of roughly 50% of treated patients at best. Furthermore, anti-viral therapy is expensive, prolonged, and associated with serious side-effects. Evidence suggests that a poor response to treatment may be the result of a suppressed anti-viral immunity due to the presence of increased numbers and activity of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg cells). We and others have recently identified fibrinogen-like protein 2 (FGL2) as a putative effector of Treg cells, which accounts for their suppressive function through binding to Fc gamma receptors (FcγR). In an experimental model of fulminant viral hepatitis, our laboratory showed that increased plasma levels of FGL2 pre- and post-viral infection were predictive of susceptibility and severity of disease. Moreover, treatment with antibody to FGL2 fully protected susceptible animals from the lethality of the virus, and adoptive transfer of wild-type Treg cells into resistant fgl2-deficient animals accelerated their mortality post-infection. In patients with HCV infection, plasma levels of FGL2 and expression of FGL2 in the liver correlated with the course and severity of the disease. Collectively, these studies suggest that FGL2 may be used as a biomarker to predict disease progression in HCV patients and be a logical target for the development of novel therapeutic approaches for the treatment of patients with HCV infection.",2010 Jul 2,"['Shalev, Itay', 'Selzner, Nazia', 'Helmy, Ahmed', 'Foerster, Katharina', 'Adeyi, Oyedele A.', 'Grant, David R.', 'Levy, Gary']",Rambam Maimonides Med J,,,True
4e6709b68cb7312fda8a1c5a2b2505d21a38a1e9,PMC,Human Coronavirus HKU1 Infection of Primary Human Type II Alveolar Epithelial Cells: Cytopathic Effects and Innate Immune Response,http://dx.doi.org/10.1371/journal.pone.0070129,PMC3722178,23894604,CC BY,"Because they are the natural target for respiratory pathogens, primary human respiratory epithelial cells provide the ideal in vitro system for isolation and study of human respiratory viruses, which display a high degree of cell, tissue, and host specificity. Human coronavirus HKU1, first discovered in 2005, has a worldwide prevalence and is associated with both upper and lower respiratory tract disease in both children and adults. Research on HCoV-HKU1 has been difficult because of its inability to be cultured on continuous cell lines and only recently it was isolated from clinical specimens using primary human, ciliated airway epithelial cells. Here we demonstrate that HCoV-HKU1 can infect and be serially propagated in primary human alveolar type II cells at the air-liquid interface. We were not able to infect alveolar type I-like cells or alveolar macrophages. Type II alveolar cells infected with HCoV-HKU1 demonstrated formation of large syncytium. At 72 hours post inoculation, HCoV-HKU1 infection of type II cells induced increased levels of mRNAs encoding IL29,CXCL10, CCL5, and IL-6 with no significant increases in the levels of IFNβ. These studies demonstrate that type II cells are a target cell for HCoV-HKU1 infection in the lower respiratory tract, that type II alveolar cells are immune-competent in response to infection exhibiting a type III interferon and proinflammatory chemokine response, and that cell to cell spread may be a major factor for spread of infection. Furthermore, these studies demonstrate that human alveolar cells can be used to isolate and study novel human respiratory viruses that cause lower respiratory tract disease.",2013 Jul 24,"['Dominguez, Samuel R.', 'Travanty, Emily A.', 'Qian, Zhaohui', 'Mason, Robert J.']",PLoS One,,,True
b6761b66c1494299587710188e9a371713d88450,PMC,Experimental Cross-Species Infection of Common Marmosets by Titi Monkey Adenovirus,http://dx.doi.org/10.1371/journal.pone.0068558,PMC3722195,23894316,CC BY,"Adenoviruses are DNA viruses that infect a number of vertebrate hosts and are associated with both sporadic and epidemic disease in humans. We previously identified a novel adenovirus, titi monkey adenovirus (TMAdV), as the cause of a fulminant pneumonia outbreak in a colony of titi monkeys (Callicebus cupreus) at a national primate center in 2009. Serological evidence of infection by TMAdV was also found in a human researcher at the facility and household family member, raising concerns for potential cross-species transmission of the virus. Here we present experimental evidence of cross-species TMAdV infection in common marmosets (Callithrix jacchus). Nasal inoculation of a cell cultured-adapted TMAdV strain into three marmosets produced an acute, mild respiratory illness characterized by low-grade fever, reduced activity, anorexia, and sneezing. An increase in virus-specific neutralization antibody titers accompanied the development of clinical signs. Although serially collected nasal swabs were positive for TMAdV for at least 8 days, all 3 infected marmosets spontaneously recovered by day 12 post-inoculation, and persistence of the virus in tissues could not be established. Thus, the pathogenesis of experimental inoculation of TMAdV in common marmosets resembled the mild, self-limiting respiratory infection typically seen in immunocompetent human hosts rather than the rapidly progressive, fatal pneumonia observed in 19 of 23 titi monkeys during the prior 2009 outbreak. These findings further establish the potential for adenovirus cross-species transmission and provide the basis for development of a monkey model useful for assessing the zoonotic potential of adenoviruses.",2013 Jul 24,"['Yu, Guixia', 'Yagi, Shigeo', 'Carrion, Ricardo', 'Chen, Eunice C.', 'Liu, Maria', 'Brasky, Kathleen M.', 'Lanford, Robert E.', 'Kelly, Kristi R.', 'Bales, Karen L.', 'Schnurr, David P.', 'Canfield, Don R.', 'Patterson, Jean L.', 'Chiu, Charles Y.']",PLoS One,,,True
ec5801ab0b12fb9b83869ca6b56261cc0ee5a458,PMC,Experimental Cross-Species Infection of Common Marmosets by Titi Monkey Adenovirus,http://dx.doi.org/10.1371/journal.pone.0068558,PMC3722195,23894316,CC BY,"Adenoviruses are DNA viruses that infect a number of vertebrate hosts and are associated with both sporadic and epidemic disease in humans. We previously identified a novel adenovirus, titi monkey adenovirus (TMAdV), as the cause of a fulminant pneumonia outbreak in a colony of titi monkeys (Callicebus cupreus) at a national primate center in 2009. Serological evidence of infection by TMAdV was also found in a human researcher at the facility and household family member, raising concerns for potential cross-species transmission of the virus. Here we present experimental evidence of cross-species TMAdV infection in common marmosets (Callithrix jacchus). Nasal inoculation of a cell cultured-adapted TMAdV strain into three marmosets produced an acute, mild respiratory illness characterized by low-grade fever, reduced activity, anorexia, and sneezing. An increase in virus-specific neutralization antibody titers accompanied the development of clinical signs. Although serially collected nasal swabs were positive for TMAdV for at least 8 days, all 3 infected marmosets spontaneously recovered by day 12 post-inoculation, and persistence of the virus in tissues could not be established. Thus, the pathogenesis of experimental inoculation of TMAdV in common marmosets resembled the mild, self-limiting respiratory infection typically seen in immunocompetent human hosts rather than the rapidly progressive, fatal pneumonia observed in 19 of 23 titi monkeys during the prior 2009 outbreak. These findings further establish the potential for adenovirus cross-species transmission and provide the basis for development of a monkey model useful for assessing the zoonotic potential of adenoviruses.",2013 Jul 24,"['Yu, Guixia', 'Yagi, Shigeo', 'Carrion, Ricardo', 'Chen, Eunice C.', 'Liu, Maria', 'Brasky, Kathleen M.', 'Lanford, Robert E.', 'Kelly, Kristi R.', 'Bales, Karen L.', 'Schnurr, David P.', 'Canfield, Don R.', 'Patterson, Jean L.', 'Chiu, Charles Y.']",PLoS One,,,False
6ea0e6352fac7379789d023be2d4b7924a98fd8b,PMC,Experimental Cross-Species Infection of Common Marmosets by Titi Monkey Adenovirus,http://dx.doi.org/10.1371/journal.pone.0068558,PMC3722195,23894316,CC BY,"Adenoviruses are DNA viruses that infect a number of vertebrate hosts and are associated with both sporadic and epidemic disease in humans. We previously identified a novel adenovirus, titi monkey adenovirus (TMAdV), as the cause of a fulminant pneumonia outbreak in a colony of titi monkeys (Callicebus cupreus) at a national primate center in 2009. Serological evidence of infection by TMAdV was also found in a human researcher at the facility and household family member, raising concerns for potential cross-species transmission of the virus. Here we present experimental evidence of cross-species TMAdV infection in common marmosets (Callithrix jacchus). Nasal inoculation of a cell cultured-adapted TMAdV strain into three marmosets produced an acute, mild respiratory illness characterized by low-grade fever, reduced activity, anorexia, and sneezing. An increase in virus-specific neutralization antibody titers accompanied the development of clinical signs. Although serially collected nasal swabs were positive for TMAdV for at least 8 days, all 3 infected marmosets spontaneously recovered by day 12 post-inoculation, and persistence of the virus in tissues could not be established. Thus, the pathogenesis of experimental inoculation of TMAdV in common marmosets resembled the mild, self-limiting respiratory infection typically seen in immunocompetent human hosts rather than the rapidly progressive, fatal pneumonia observed in 19 of 23 titi monkeys during the prior 2009 outbreak. These findings further establish the potential for adenovirus cross-species transmission and provide the basis for development of a monkey model useful for assessing the zoonotic potential of adenoviruses.",2013 Jul 24,"['Yu, Guixia', 'Yagi, Shigeo', 'Carrion, Ricardo', 'Chen, Eunice C.', 'Liu, Maria', 'Brasky, Kathleen M.', 'Lanford, Robert E.', 'Kelly, Kristi R.', 'Bales, Karen L.', 'Schnurr, David P.', 'Canfield, Don R.', 'Patterson, Jean L.', 'Chiu, Charles Y.']",PLoS One,,,False
5b070d94a23c10061ed3f494fad703429fe8c1a0,PMC,Experimental Cross-Species Infection of Common Marmosets by Titi Monkey Adenovirus,http://dx.doi.org/10.1371/journal.pone.0068558,PMC3722195,23894316,CC BY,"Adenoviruses are DNA viruses that infect a number of vertebrate hosts and are associated with both sporadic and epidemic disease in humans. We previously identified a novel adenovirus, titi monkey adenovirus (TMAdV), as the cause of a fulminant pneumonia outbreak in a colony of titi monkeys (Callicebus cupreus) at a national primate center in 2009. Serological evidence of infection by TMAdV was also found in a human researcher at the facility and household family member, raising concerns for potential cross-species transmission of the virus. Here we present experimental evidence of cross-species TMAdV infection in common marmosets (Callithrix jacchus). Nasal inoculation of a cell cultured-adapted TMAdV strain into three marmosets produced an acute, mild respiratory illness characterized by low-grade fever, reduced activity, anorexia, and sneezing. An increase in virus-specific neutralization antibody titers accompanied the development of clinical signs. Although serially collected nasal swabs were positive for TMAdV for at least 8 days, all 3 infected marmosets spontaneously recovered by day 12 post-inoculation, and persistence of the virus in tissues could not be established. Thus, the pathogenesis of experimental inoculation of TMAdV in common marmosets resembled the mild, self-limiting respiratory infection typically seen in immunocompetent human hosts rather than the rapidly progressive, fatal pneumonia observed in 19 of 23 titi monkeys during the prior 2009 outbreak. These findings further establish the potential for adenovirus cross-species transmission and provide the basis for development of a monkey model useful for assessing the zoonotic potential of adenoviruses.",2013 Jul 24,"['Yu, Guixia', 'Yagi, Shigeo', 'Carrion, Ricardo', 'Chen, Eunice C.', 'Liu, Maria', 'Brasky, Kathleen M.', 'Lanford, Robert E.', 'Kelly, Kristi R.', 'Bales, Karen L.', 'Schnurr, David P.', 'Canfield, Don R.', 'Patterson, Jean L.', 'Chiu, Charles Y.']",PLoS One,,,False
38709b5c18e24c3287a6b1b97ddbe8899cdab432,PMC,Use of Hangeul Twitter to Track and Predict Human Influenza Infection,http://dx.doi.org/10.1371/journal.pone.0069305,PMC3722273,23894447,CC BY,"Influenza epidemics arise through the accumulation of viral genetic changes. The emergence of new virus strains coincides with a higher level of influenza-like illness (ILI), which is seen as a peak of a normal season. Monitoring the spread of an epidemic influenza in populations is a difficult and important task. Twitter is a free social networking service whose messages can improve the accuracy of forecasting models by providing early warnings of influenza outbreaks. In this study, we have examined the use of information embedded in the Hangeul Twitter stream to detect rapidly evolving public awareness or concern with respect to influenza transmission and developed regression models that can track levels of actual disease activity and predict influenza epidemics in the real world. Our prediction model using a delay mode provides not only a real-time assessment of the current influenza epidemic activity but also a significant improvement in prediction performance at the initial phase of ILI peak when prediction is of most importance.",2013 Jul 24,"['Kim, Eui-Ki', 'Seok, Jong Hyeon', 'Oh, Jang Seok', 'Lee, Hyong Woo', 'Kim, Kyung Hyun']",PLoS One,,,True
d5fbbe644c1b4979ea69e57eac5061ce2e3a71ca,PMC,Use of Hangeul Twitter to Track and Predict Human Influenza Infection,http://dx.doi.org/10.1371/journal.pone.0069305,PMC3722273,23894447,CC BY,"Influenza epidemics arise through the accumulation of viral genetic changes. The emergence of new virus strains coincides with a higher level of influenza-like illness (ILI), which is seen as a peak of a normal season. Monitoring the spread of an epidemic influenza in populations is a difficult and important task. Twitter is a free social networking service whose messages can improve the accuracy of forecasting models by providing early warnings of influenza outbreaks. In this study, we have examined the use of information embedded in the Hangeul Twitter stream to detect rapidly evolving public awareness or concern with respect to influenza transmission and developed regression models that can track levels of actual disease activity and predict influenza epidemics in the real world. Our prediction model using a delay mode provides not only a real-time assessment of the current influenza epidemic activity but also a significant improvement in prediction performance at the initial phase of ILI peak when prediction is of most importance.",2013 Jul 24,"['Kim, Eui-Ki', 'Seok, Jong Hyeon', 'Oh, Jang Seok', 'Lee, Hyong Woo', 'Kim, Kyung Hyun']",PLoS One,,,False
73104fbdc161f1cea305271bdd1a2f11bf49bdc2,PMC,Use of Hangeul Twitter to Track and Predict Human Influenza Infection,http://dx.doi.org/10.1371/journal.pone.0069305,PMC3722273,23894447,CC BY,"Influenza epidemics arise through the accumulation of viral genetic changes. The emergence of new virus strains coincides with a higher level of influenza-like illness (ILI), which is seen as a peak of a normal season. Monitoring the spread of an epidemic influenza in populations is a difficult and important task. Twitter is a free social networking service whose messages can improve the accuracy of forecasting models by providing early warnings of influenza outbreaks. In this study, we have examined the use of information embedded in the Hangeul Twitter stream to detect rapidly evolving public awareness or concern with respect to influenza transmission and developed regression models that can track levels of actual disease activity and predict influenza epidemics in the real world. Our prediction model using a delay mode provides not only a real-time assessment of the current influenza epidemic activity but also a significant improvement in prediction performance at the initial phase of ILI peak when prediction is of most importance.",2013 Jul 24,"['Kim, Eui-Ki', 'Seok, Jong Hyeon', 'Oh, Jang Seok', 'Lee, Hyong Woo', 'Kim, Kyung Hyun']",PLoS One,,,False
ccaafc13b2c1551dce74e1a7fe3e43cea5228732,PMC,A Network Integration Approach to Predict Conserved Regulators Related to Pathogenicity of Influenza and SARS-CoV Respiratory Viruses,http://dx.doi.org/10.1371/journal.pone.0069374,PMC3723910,23935999,CC0,"Respiratory infections stemming from influenza viruses and the Severe Acute Respiratory Syndrome corona virus (SARS-CoV) represent a serious public health threat as emerging pandemics. Despite efforts to identify the critical interactions of these viruses with host machinery, the key regulatory events that lead to disease pathology remain poorly targeted with therapeutics. Here we implement an integrated network interrogation approach, in which proteome and transcriptome datasets from infection of both viruses in human lung epithelial cells are utilized to predict regulatory genes involved in the host response. We take advantage of a novel “crowd-based” approach to identify and combine ranking metrics that isolate genes/proteins likely related to the pathogenicity of SARS-CoV and influenza virus. Subsequently, a multivariate regression model is used to compare predicted lung epithelial regulatory influences with data derived from other respiratory virus infection models. We predicted a small set of regulatory factors with conserved behavior for consideration as important components of viral pathogenesis that might also serve as therapeutic targets for intervention. Our results demonstrate the utility of integrating diverse ‘omic datasets to predict and prioritize regulatory features conserved across multiple pathogen infection models.",2013 Jul 25,"['Mitchell, Hugh D.', 'Eisfeld, Amie J.', 'Sims, Amy C.', 'McDermott, Jason E.', 'Matzke, Melissa M.', 'Webb-Robertson, Bobbi-Jo M.', 'Tilton, Susan C.', 'Tchitchek, Nicolas', 'Josset, Laurence', 'Li, Chengjun', 'Ellis, Amy L.', 'Chang, Jean H.', 'Heegel, Robert A.', 'Luna, Maria L.', 'Schepmoes, Athena A.', 'Shukla, Anil K.', 'Metz, Thomas O.', 'Neumann, Gabriele', 'Benecke, Arndt G.', 'Smith, Richard D.', 'Baric, Ralph S.', 'Kawaoka, Yoshihiro', 'Katze, Michael G.', 'Waters, Katrina M.']",PLoS One,,,True
fb8dfa6988a6f08b4b64a0d5c7843c854a8328d0,PMC,Computational modeling of the p7 monomer from HCV and its interaction with small molecule drugs,http://dx.doi.org/10.1186/2193-1801-2-324,PMC3724979,23961398,CC BY,"Hepatitis C virus p7 protein is a 63 amino acid polytopic protein with two transmembrane domains (TMDs) and one of the prime targets for anti HCV drug development. A bio-inspired modeling pathway is used to generate plausible computational models of the two TMDs forming the monomeric protein model. A flexible region between Leu-13 and Gly-15 is identified for TMD1(1-32) and a region around Gly-46 to Trp-48 for TMD2(36-58). Mutations of the tyrosine residues in TMD2(36-58) into phenylalanine and serine are simulated to identify their role in shaping TMD2. Lowest energy structures of the two TMDs connected with the loop residues are used for a posing study in which small molecule drugs BIT225, amantadine, rimantadine and NN-DNJ, are identified to bind to the loop region. BIT225 is identified to interact with the backbone of the functionally important residues Arg-35 and Trp-36. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-324) contains supplementary material, which is available to authorized users.",2013 Jul 18,"['Wang, Yi-Ting', 'Hsu, Hao-Jen', 'Fischer, Wolfgang B']",Springerplus,,,True
626267a319f0390205d0e2c5fa2c93e7402f274b,PMC,Expression of Recombinant Antibodies,http://dx.doi.org/10.3389/fimmu.2013.00217,PMC3725456,23908655,CC BY,"Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with “human-like” post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.",2013 Jul 29,"['Frenzel, André', 'Hust, Michael', 'Schirrmann, Thomas']",Front Immunol,,,True
fc29089acf4b70c64a5a5e4ea64a318e8d52edbb,PMC,Transdifferentiation of MALME-3M and MCF-7 Cells toward Adipocyte-like Cells is Dependent on Clathrin-mediated Endocytosis,http://dx.doi.org/10.1186/2193-1801-1-44,PMC3725915,23961369,CC BY,"ABSTRACT: Enforced cell transdifferentiation of human cancer cells is a promising alternative to conventional chemotherapy. We previously identified albumin-associated lipid- and, more specifically, saturated fatty acid-induced transdifferentiation programs in human cancer cells (HCCLs). In this study, we further characterized the adipocyte-like cells, resulting from the transdifferentiation of human cancer cell lines MCF-7 and MALME-3M, and proposed a common mechanistic approach for these transdifferentiating programs. We showed the loss of pigmentation in MALME-3M cells treated with albumin-associated lipids, based on electron microscopic analysis, and the overexpression of perilipin 2 (PLIN2) by western blotting in MALME-3M and MCF-7 cells treated with unsaturated fatty acids. Comparing the gene expression profiles of naive melanoma MALME-3M cells and albumin-associated lipid-treated cells, based on RNA sequencing, we confirmed the transcriptional upregulation of some key adipogenic gene markers and also an alternative splicing of the adipogenic master regulator PPARG, that is probably related to the reported up regulated expression of the protein. Most importantly, these results also showed the upregulation of genes responsible for Clathrin (CLTC) and other adaptor-related proteins. An increase in CLTC expression in the transdifferentiated cells was confirmed by western blotting. Inactivation of CLTC by chlorpromazine (CHP), an inhibitor of CTLC mediated endocytosis (CME), and gene silencing by siRNAs, partially reversed the accumulation of neutral lipids observed in the transdifferentiated cells. These findings give a deeper insight into the phenotypic changes observed in HCCL to adipocyte-like transdifferentiation and point towards CME as a key pathway in distinct transdifferentiation programs. DISCLOSURES: Simon C and Aguilar-Gallardo C are co-inventors of the International Patent Application No. PCT/EP2011/004941 entitled “Methods for tumor treatment and adipogenesis differentiation”. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-1-44) contains supplementary material, which is available to authorized users.",2012 Oct 30,"['Carcel-Trullols, Jaime', 'Aguilar-Gallardo, Cristóbal', 'Garcia-Alcalde, Fernando', 'Pardo-Cea, Miguel Angel', 'Dopazo, Joaquin', 'Conesa, Ana', 'Simón, Carlos']",Springerplus,,,True
a11eb58857b227cdd846083d87304eef58b52ac2,PMC,Diverse activation of microglia by chemokine (C-C motif) ligand 2 overexpression in brain,http://dx.doi.org/10.1186/1742-2094-10-86,PMC3726363,23866683,CC BY,"BACKGROUND: The chemokine (C-C motif) ligand 2 (CCL2) is a monocyte chemoattractant protein that mediates macrophage recruitment and migration during peripheral and central nervous system (CNS) inflammation. METHODS: To determine the impact of CCL2 in inflammation in vivo and to elucidate the CCL2-induced polarization of activated brain microglia, we delivered CCL2 into the brains of wild-type mice via recombinant adeno-associated virus serotype 9 (rAAV-9) driven by the chicken β-actin promoter. We measured microglial activation using histological and chemical measurement and recruitment of monocytes using histology and flow cytometry. RESULTS: The overexpression of CCL2 in the CNS induced significant activation of brain resident microglia. CD45 and major histocompatibility complex class II immunoreactivity significantly increased at the sites of CCL2 administration. Histological characterization of the microglial phenotype revealed the elevation of “classically activated” microglial markers, such as calgranulin B and IL-1β, as well as markers associated with “alternative activation” of microglia, including YM1 and arginase 1. The protein expression profile in the hippocampus demonstrated markedly increased levels of IL-6, GM-CSF and eotaxin (CCL-11) in response to CCL2, but no changes in the levels of other cytokines, including TNF-α and IFN-γ. Moreover, real-time PCR analysis confirmed increases in mRNA levels of gene transcripts associated with neuroinflammation following CCL2 overexpression. Finally, we investigated the chemotactic properties of CCL2 in vivo by performing adoptive transfer of bone marrow–derived cells (BMDCs) isolated from donor mice that ubiquitously expressed green fluorescent protein. Flow cytometry and histological analyses indicated that BMDCs extravasated into brain parenchyma and colabeled with microglial markers. CONCLUSION: Taken together, our results suggest that CCL2 strongly activates resident microglia in the brain. Both pro- and anti-inflammatory activation of microglia were prominent, with no bias toward the M1 or M2 phenotype in the activated cells. As expected, CCL2 overexpression actively recruited circulating monocytes into the CNS. Thus, CCL2 expression in mouse brain induces microglial activation and represents an efficient method for recruitment of peripheral macrophages.",2013 Jul 17,"['Selenica, Maj-Linda B', 'Alvarez, Jennifer A', 'Nash, Kevin R', 'Lee, Daniel C', 'Cao, Chuanhai', 'Lin, Xiaoyang', 'Reid, Patrick', 'Mouton, Peter R', 'Morgan, Dave', 'Gordon, Marcia N']",J Neuroinflammation,,,True
58b271e61f06e148dd80d5dbf0c037118dcc9963,PMC,Changes in codon-pair bias of human immunodeficiency virus type 1 have profound effects on virus replication in cell culture,http://dx.doi.org/10.1186/1742-4690-10-78,PMC3726367,23885919,CC BY,"BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) has a biased nucleotide composition different from human genes. This raises the question of how evolution has chosen the nucleotide sequence of HIV-1 that is observed today, or to what extent the actual encoding contributes to virus replication capacity, evolvability and pathogenesis. Here, we applied the previously described synthetic attenuated virus engineering (SAVE) approach to HIV-1. RESULTS: Using synonymous codon pairs, we rationally recoded and codon pair–optimized and deoptimized different moieties of the HIV-1 gag and pol genes. Deoptimized viruses had significantly lower viral replication capacity in MT-4 and peripheral blood mononuclear cells (PBMCs). Varying degrees of ex vivo attenuation were obtained, depending upon both the specific deoptimized region and the number of deoptimized codons. A protease optimized virus carrying 38 synonymous mutations was not attenuated and displayed a replication capacity similar to that of the wild-type virus in MT-4 cells and PBMCs. Although attenuation is based on several tens of nucleotide changes, deoptimized HIV-1 reverted to wild-type virulence after serial passages in MT-4 cells. Remarkably, no reversion was observed in the optimized virus. CONCLUSION: These data demonstrate that SAVE is a useful strategy to phenotypically affect the replicative properties of HIV-1.",2013 Jul 25,"['Martrus, Gloria', 'Nevot, Maria', 'Andres, Cristina', 'Clotet, Bonaventura', 'Martinez, Miguel Angel']",Retrovirology,,,True
710dd69c07a692bbdcd7261bb4508cd9935556c6,PMC,Regulation of Coronaviral Poly(A) Tail Length during Infection,http://dx.doi.org/10.1371/journal.pone.0070548,PMC3726627,23923003,CC BY,"The positive-strand coronavirus genome of ~30 kilobase in length and subgenomic (sg) mRNAs of shorter lengths, are 5’ and 3’-co-terminal by virtue of a common 5’-capped leader and a common 3’-polyadenylated untranslated region. Here, by ligating head-to-tail viral RNAs from bovine coronavirus-infected cells and sequencing across the ligated junctions, it was learned that at the time of peak viral RNA synthesis [6 hours postinfection (hpi)] the 3’ poly(A) tail on genomic and sgmRNAs is ~65 nucleotides (nt) in length. Surprisingly, this length was found to vary throughout infection from ~45 nt immediately after virus entry (at 0 to 4 hpi) to ~65 nt later on (at 6 h to 9 hpi) and from ~65 nt (at 6 h to 9 hpi) to ~30 nt (at 120-144 hpi). With the same method, poly(U) sequences of the same lengths were simultaneously found on the ligated viral negative-strand RNAs. Functional analyses of poly(A) tail length on specific viral RNA species, furthermore, revealed that translation, in vivo, of RNAs with the longer poly(A) tail was enhanced over those with the shorter poly(A). Although the mechanisms by which the tail lengths vary is unknown, experimental results together suggest that the length of the poly(A) and poly(U) tails is regulated. One potential function of regulated poly(A) tail length might be that for the coronavirus genome a longer poly(A) favors translation. The regulation of coronavirus translation by poly(A) tail length resembles that during embryonal development suggesting there may be mechanistic parallels.",2013 Jul 29,"['Wu, Hung-Yi', 'Ke, Ting-Yung', 'Liao, Wei-Yu', 'Chang, Nai-Yun']",PLoS One,,,True
5d04b1e66045a858dd72847b88dcc6a280da3165,PMC,"Etiological analysis and predictive diagnostic model building of community-acquired pneumonia in adult outpatients in Beijing, China",http://dx.doi.org/10.1186/1471-2334-13-309,PMC3728139,23834931,CC BY,"BACKGROUND: Etiological epidemiology and diagnosis are important issues in adult community-acquired pneumonia (CAP), and identifying pathogens based on patient clinical features is especially a challenge. CAP-associated main pathogens in adults include viruses as well as bacteria. However, large-scale epidemiological investigations of adult viral CAP in China are still lacking. In this study, we analyzed the etiology of adult CAP in Beijing, China and constructed diagnostic models based on combinations of patient clinical factors. METHODS: A multicenter cohort was established with 500 adult CAP outpatients enrolled in Beijing between November 2010 to October 2011. Multiplex and quantitative real-time fluorescence PCR were used to detect 15 respiratory viruses and mycoplasma pneumoniae, respectively. Bacteria were detected with culture and enzyme immunoassay of the Streptococcus pneumoniae urinary antigen. Univariate analysis, multivariate analysis, discriminatory analysis and Receiver Operating Characteristic (ROC) curves were used to build predictive models for etiological diagnosis of adult CAP. RESULTS: Pathogens were detected in 54.2% (271/500) of study patients. Viruses accounted for 36.4% (182/500), mycoplasma pneumoniae for 18.0% (90/500) and bacteria for 14.4% (72/500) of the cases. In 182 of the patients with viruses, 219 virus strains were detected, including 166 single and 53 mixed viral infections. Influenza A virus represented the greatest proportion with 42.0% (92/219) and 9.1% (20/219) in single and mixed viral infections, respectively. Factors selected for the predictive etiological diagnostic model of viral CAP included cough, dyspnea, absence of chest pain and white blood cell count (4.0-10.0) × 10(9)/L, and those of mycoplasma pneumoniae CAP were being younger than 45 years old and the absence of a coexisting disease. However, these models showed low accuracy levels for etiological diagnosis (areas under ROC curve for virus and mycoplasma pneumoniae were both 0.61, P < 0.05). CONCLUSIONS: Greater consideration should be given to viral and mycoplasma pneumoniae infections in adult CAP outpatients. While predictive etiological diagnostic models of viral and mycoplasma pneumoniae based on combinations of demographic and clinical factors may provide indications of etiology, diagnostic confirmation of CAP remains dependent on laboratory pathogen test results.",2013 Jul 9,"['Liu, Ya-Fen', 'Gao, Yan', 'Chen, Mei-Fang', 'Cao, Bin', 'Yang, Xiao-Hua', 'Wei, Lai']",BMC Infect Dis,,,True
c4e5c3ffe90100931729abab4aa1155d8c145816,PMC,Protective Efficacy of VP1-Specific Neutralizing Antibody Associated with a Reduction of Viral Load and Pro-Inflammatory Cytokines in Human SCARB2-Transgenic Mice,http://dx.doi.org/10.1371/journal.pone.0069858,PMC3728341,23936115,CC BY,"Hand-foot-mouth diseases (HFMD) caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16) in children have now become a severe public health issue in the Asian-Pacific region. Recently we have successfully developed transgenic mice expressing human scavenger receptor class B member 2 (hSCARB2, a receptor of EV71 and CVA16) as an animal model for evaluating the pathogenesis of enterovirus infections. In this study, hSCARB2-transgenic mice were used to investigate the efficacy conferred by a previously described EV71 neutralizing antibody, N3. A single injection of N3 effectively inhibited the HFMD-like skin scurfs in mice pre-infected with clinical isolate of EV71 E59 (B4 genotype) or prevented severe limb paralysis and death in mice pre-inoculated with 5746 (C2 genotype). This protection was correlated with remarkable reduction of viral loads in the brain, spinal cord and limb muscles. Accumulated viral loads and the associated pro-inflammatory cytokines were all reduced. The protective efficacy of N3 was not observed in animals challenged with CVA16. This could be due to dissimilarity sequences of the neutralizing epitope found in CVA16. These results indicate N3 could be useful in treating severe EV71 infections and the hSCARB2-transgenic mouse could be used to evaluate the protective efficacy of potential anti-enterovirus agent candidates.",2013 Jul 30,"['Chang, Hsuen-Wen', 'Lin, Yi-Wen', 'Ho, Hui-Min', 'Lin, Min-Han', 'Liu, Chia-Chyi', 'Shao, Hsiao-Yun', 'Chong, Pele', 'Sia, Charles', 'Chow, Yen-Hung']",PLoS One,,,True
943491914a5f52c713070accbde7e0e868771e91,PMC,Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies,http://dx.doi.org/10.1371/journal.pone.0069649,PMC3729563,23936066,CC BY,"Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN) or the intrapulmonary (IPL) route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses.",2013 Jul 31,"['Liu, Heng', 'Patil, Harshad P.', 'de Vries-Idema, Jacqueline', 'Wilschut, Jan', 'Huckriede, Anke']",PLoS One,,,True
0e5ca6286111f518f4d41267587324c92a902aa2,PMC,Arenavirus budding resulting from viral-protein-associated cell membrane curvature,http://dx.doi.org/10.1098/rsif.2013.0403,PMC3730687,23864502,CC BY,"Viral replication occurs within cells, with release (and onward infection) primarily achieved through two alternative mechanisms: lysis, in which virions emerge as the infected cell dies and bursts open; or budding, in which virions emerge gradually from a still living cell by appropriating a small part of the cell membrane. Virus budding is a poorly understood process that challenges current models of vesicle formation. Here, a plausible mechanism for arenavirus budding is presented, building on recent evidence that viral proteins embed in the inner lipid layer of the cell membrane. Experimental results confirm that viral protein is associated with increased membrane curvature, whereas a mathematical model is used to show that localized increases in curvature alone are sufficient to generate viral buds. The magnitude of the protein-induced curvature is calculated from the size of the amphipathic region hypothetically removed from the inner membrane as a result of translation, with a change in membrane stiffness estimated from observed differences in virion deformation as a result of protein depletion. Numerical results are based on experimental data and estimates for three arenaviruses, but the mechanisms described are more broadly applicable. The hypothesized mechanism is shown to be sufficient to generate spontaneous budding that matches well both qualitatively and quantitatively with experimental observations.",2013 Sep 6,"['Schley, David', 'Whittaker, Robert J.', 'Neuman, Benjamin W.']",J R Soc Interface,,,True
492ae848b7e2b20047ac406af1c7712ea6255461,PMC,Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent Varicella-Zoster Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1003512,PMC3731237,23935496,CC0,"Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.",2013 Aug 1,"['Goodwin, Thomas J.', 'McCarthy, Maureen', 'Osterrieder, Nikolaus', 'Cohrs, Randall J.', 'Kaufer, Benedikt B.']",PLoS Pathog,,,True
0080d3bd9fb92e022c27715c2d1249042aa998b8,PMC,Rational Design of a Live Attenuated Dengue Vaccine: 2′-O-Methyltransferase Mutants Are Highly Attenuated and Immunogenic in Mice and Macaques,http://dx.doi.org/10.1371/journal.ppat.1003521,PMC3731252,23935499,CC BY,"Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year. Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue, resulting in a continuously increasing number of cases. A cost-effective, safe vaccine conferring protection with ideally a single injection could stop dengue transmission. Current vaccine candidates require several booster injections or do not provide protection against all four serotypes. Here we demonstrate that dengue virus mutants lacking 2′-O-methyltransferase activity are highly sensitive to type I IFN inhibition. The mutant viruses are attenuated in mice and rhesus monkeys and elicit a strong adaptive immune response. Monkeys immunized with a single dose of 2′-O-methyltransferase mutant virus showed 100% sero-conversion even when a dose as low as 1,000 plaque forming units was administrated. Animals were fully protected against a homologous challenge. Furthermore, mosquitoes feeding on blood containing the mutant virus were not infected, whereas those feeding on blood containing wild-type virus were infected and thus able to transmit it. These results show the potential of 2′-O-methyltransferase mutant virus as a safe, rationally designed dengue vaccine that restrains itself due to the increased susceptibility to the host's innate immune response.",2013 Aug 1,"['Züst, Roland', 'Dong, Hongping', 'Li, Xiao-Feng', 'Chang, David C.', 'Zhang, Bo', 'Balakrishnan, Thavamalar', 'Toh, Ying-Xiu', 'Jiang, Tao', 'Li, Shi-Hua', 'Deng, Yong-Qiang', 'Ellis, Brett R.', 'Ellis, Esther M.', 'Poidinger, Michael', 'Zolezzi, Francesca', 'Qin, Cheng-Feng', 'Shi, Pei-Yong', 'Fink, Katja']",PLoS Pathog,,,True
088571fa032ef5eb915d17b62e106a698a301f2c,PMC,Characterization of Synthetic Chikungunya Viruses Based on the Consensus Sequence of Recent E1-226V Isolates,http://dx.doi.org/10.1371/journal.pone.0071047,PMC3731263,23936484,CC BY,"Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that re-emerged in 2004 and has caused massive outbreaks in recent years. The lack of a licensed vaccine or treatment options emphasize the need to obtain more insight into the viral life cycle and CHIKV-host interactions. Infectious cDNA clones are important tools for such studies, and for mechanism of action studies on antiviral compounds. Existing CHIKV cDNA clones are based on a single genome from an individual clinical isolate, which is expected to have evolved specific characteristics in response to the host environment, and possibly also during subsequent cell culture passaging. To obtain a virus expected to have the general characteristics of the recent E1-226V CHIKV isolates, we have constructed a new CHIKV full-length cDNA clone, CHIKV LS3, based on the consensus sequence of their aligned genomes. Here we report the characterization of this synthetic virus and a green fluorescent protein-expressing variant (CHIKV LS3-GFP). Their characteristics were compared to those of natural strain ITA07-RA1, which was isolated during the 2007 outbreak in Italy. In cell culture the synthetic viruses displayed phenotypes comparable to the natural isolate, and in a mouse model they caused lethal infections that were indistinguishable from infections with a natural strain. Compared to ITA07-RA1 and clinical isolate NL10/152, the synthetic viruses displayed similar sensitivities to several antiviral compounds. 3-deaza-adenosine was identified as a new inhibitor of CHIKV replication. Cyclosporin A had no effect on CHIKV replication, suggesting that cyclophilins -opposite to what was found for other +RNA viruses- do not play an essential role in CHIKV replication. The characterization of the consensus sequence-based synthetic viruses and their comparison to natural isolates demonstrated that CHIKV LS3 and LS3-GFP are suitable and representative tools to study CHIKV-host interactions, screen for antiviral compounds and unravel their mode of action.",2013 Aug 1,"['Scholte, Florine E. M.', 'Tas, Ali', 'Martina, Byron E. E.', 'Cordioli, Paolo', 'Narayanan, Krishna', 'Makino, Shinji', 'Snijder, Eric J.', 'van Hemert, Martijn J.']",PLoS One,,,True
a2bcb2cb93937aaa45834b4a1fa568334c58ae96,PMC,Characterization of Synthetic Chikungunya Viruses Based on the Consensus Sequence of Recent E1-226V Isolates,http://dx.doi.org/10.1371/journal.pone.0071047,PMC3731263,23936484,CC BY,"Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that re-emerged in 2004 and has caused massive outbreaks in recent years. The lack of a licensed vaccine or treatment options emphasize the need to obtain more insight into the viral life cycle and CHIKV-host interactions. Infectious cDNA clones are important tools for such studies, and for mechanism of action studies on antiviral compounds. Existing CHIKV cDNA clones are based on a single genome from an individual clinical isolate, which is expected to have evolved specific characteristics in response to the host environment, and possibly also during subsequent cell culture passaging. To obtain a virus expected to have the general characteristics of the recent E1-226V CHIKV isolates, we have constructed a new CHIKV full-length cDNA clone, CHIKV LS3, based on the consensus sequence of their aligned genomes. Here we report the characterization of this synthetic virus and a green fluorescent protein-expressing variant (CHIKV LS3-GFP). Their characteristics were compared to those of natural strain ITA07-RA1, which was isolated during the 2007 outbreak in Italy. In cell culture the synthetic viruses displayed phenotypes comparable to the natural isolate, and in a mouse model they caused lethal infections that were indistinguishable from infections with a natural strain. Compared to ITA07-RA1 and clinical isolate NL10/152, the synthetic viruses displayed similar sensitivities to several antiviral compounds. 3-deaza-adenosine was identified as a new inhibitor of CHIKV replication. Cyclosporin A had no effect on CHIKV replication, suggesting that cyclophilins -opposite to what was found for other +RNA viruses- do not play an essential role in CHIKV replication. The characterization of the consensus sequence-based synthetic viruses and their comparison to natural isolates demonstrated that CHIKV LS3 and LS3-GFP are suitable and representative tools to study CHIKV-host interactions, screen for antiviral compounds and unravel their mode of action.",2013 Aug 1,"['Scholte, Florine E. M.', 'Tas, Ali', 'Martina, Byron E. E.', 'Cordioli, Paolo', 'Narayanan, Krishna', 'Makino, Shinji', 'Snijder, Eric J.', 'van Hemert, Martijn J.']",PLoS One,,,False
baa8420ed8f9d0dc7ba81b519eda2c3fe91291b8,PMC,The First Transmembrane Domain of Lipid Phosphatase SAC1 Promotes Golgi Localization,http://dx.doi.org/10.1371/journal.pone.0071112,PMC3731292,23936490,CC BY,"The lipid phosphatase Sac1 cycles between endoplasmic reticulum and cisternal Golgi compartments. In proliferating mammalian cells, a canonical dilysine motif at the C-terminus of Sac1 is required for coatomer complex-I (COP-I)-binding and continuous retrieval to the ER. Starvation triggers accumulation of Sac1 at the Golgi. The mechanism responsible for Golgi retention of Sac1 is unknown. Here we show that the first of the two transmembrane regions in human SAC1 (TM1) functions in Golgi localization. A minimal construct containing only TM1 and the adjacent flanking sequences is concentrated at the Golgi. Transplanting TM1 into transferrin receptor 2 (TfR2) induces Golgi accumulation of this normally plasma membrane and endosomal protein, indicating that TM1 is sufficient for Golgi localization. In addition, we determined that the N-terminal cytoplasmic domain of SAC1 also promotes Golgi localization, even when TM1 is mutated or absent. We conclude that the distribution of SAC1 within the Golgi is controlled via both passive membrane thickness-dependent partitioning of TM1 and a retention mechanism that requires the N-terminal cytoplasmic region.",2013 Aug 1,"['Wang, Jinzhi', 'Chen, Juxing', 'Enns, Caroline A.', 'Mayinger, Peter']",PLoS One,,,True
f81ae57f3c989bf53683a523da0a1799ebd19862,PMC,Rapid and Sensitive Detection of Novel Avian-Origin Influenza A (H7N9) Virus by Reverse Transcription Loop-Mediated Isothermal Amplification Combined with a Lateral-Flow Device,http://dx.doi.org/10.1371/journal.pone.0069941,PMC3731295,23936359,CC BY,"A severe disease in humans caused by a novel avian-origin influenza A (H7N9) virus emerged in China recently, which has caused at least 128 cases and 26 deaths. Rapid detection of the novel H7N9 virus is urgently needed to differentiate the disease from other infections, and to facilitate infection control as well as epidemiologic investigations. In this study, a reverse transcription loop-mediated isothermal amplification combined with a lateral flow device (RT-LAMP-LFD) assay to rapidly detect H7N9 virus was developed and evaluated. The RT-LAMP primers were designed to target the haemagglutinin (HA) and neuraminidase (NA) genes of H7N9 virus. Results of 10-fold dilution series assays showed that analysis of RT-LAMP products by the LFD method was as sensitive as real-time turbidity detection, and that the analytic sensitivities of the HA and NA RT-LAMP assays were both 10 copies of synthetic RNA. Furthermore, both the assays showed 100% clinical specificity for identification of H7N9 virus. The performance characteristics of the RT-LAMP-LFD assay were evaluated with 80 clinical specimens collected from suspected H7N9 patients. The NA RT-LAMP-LFD assay was more sensitive than real time RT-PCR assay. Compared with a combination of virus culture and real-time RT-PCR, the sensitivity, specificity, positive predictive value, and negative predictive value of the RT-LAMP-LFD assay were all 100%. Overall, The RT-LAMP-LFD assay established in this study can be used as a reliable method for early diagnosis of the avian-origin influenza A (H7N9) virus infection.",2013 Aug 1,"['Ge, Yiyue', 'Wu, Bin', 'Qi, Xian', 'Zhao, Kangchen', 'Guo, Xiling', 'Zhu, Yefei', 'Qi, Yuhua', 'Shi, Zhiyang', 'Zhou, Minghao', 'Wang, Hua', 'Cui, Lunbiao']",PLoS One,,,True
5eb39003823f5339573f8f9ed82eaf7763feda68,PMC,Manipulation of the Porcine Epidemic Diarrhea Virus Genome Using Targeted RNA Recombination,http://dx.doi.org/10.1371/journal.pone.0069997,PMC3732256,23936367,CC BY,"Porcine epidemic diarrhea virus (PEDV) causes severe economic losses in the swine industry in China and other Asian countries. Infection usually leads to an acute, often lethal diarrhea in piglets. Despite the impact of the disease, no system is yet available to manipulate the viral genome which has severely hampered research on this virus until today. We have established a reverse genetics system for PEDV based on targeted RNA recombination that allows the modification of the 3′-end of the viral genome, which encodes the structural proteins and the ORF3 protein. Using this system, we deleted the ORF3 gene entirely from the viral genome and showed that the ORF3 protein is not essential for replication of the virus in vitro. In addition, we inserted heterologous genes (i.e. the GFP and Renilla luciferase genes) at two positions in the viral genome, either as an extra expression cassette or as a replacement for the ORF3 gene. We demonstrated the expression of both GFP and Renilla luciferase as well as the application of these viruses by establishing a convenient and rapid virus neutralization assay. The new PEDV reverse genetics system will enable functional studies of the structural proteins and the accessory ORF3 protein and will allow the rational design and development of next generation PEDV vaccines.",2013 Aug 2,"['Li, Chunhua', 'Li, Zhen', 'Zou, Yong', 'Wicht, Oliver', 'van Kuppeveld, Frank J. M.', 'Rottier, Peter J. M.', 'Bosch, Berend Jan']",PLoS One,,,True
2a7617954fb5dc66e2d7d62b1e5ea2c54f4e02ce,PMC,Modulation of airway epithelial cell functions by Pidotimod: NF-kB cytoplasmatic expression and its nuclear translocation are associated with an increased TLR-2 expression,http://dx.doi.org/10.1186/1824-7288-39-29,PMC3733658,23663325,CC BY,"BACKGROUND: Recurrent respiratory infections are one of the most important causes of morbidity in childhood. When immune functions are still largely immature, the airway epithelium plays a primary defensive role since, besides providing a physical barrier, it is also involved in the innate and the adaptive immune responses. A study was therefore designed to evaluate in vitro whether pidotimod, a synthetic dipeptide able to stimulate the inflammatory and immune effector cells, could activate bronchial epithelial cell functions involved in response to infections. METHODS: BEAS-2B cell line (human bronchial epithelial cells infected with a replication-defective Adenovirus 12-SV40 virus hybrid) were cultured in the presence of pidotimod, with or without tumor necrosis factor (TNF)-α or zymosan to assess: a) intercellular adhesion molecule (ICAM)-1 expression, by flow cytometry; b) toll-like receptor (TLR)-2 expression and production, by immunofluorescence flow cytometry and western blotting; d) interleukin (IL)-8 release, by enzyme-linked immunosorbent assay (ELISA); e) activated extracellular-signal-regulated kinase (ERK1/2) phosphorylation and nuclear factor-kappa B (NF-kB) activation, by western blotting. RESULTS: The constitutive expression of ICAM-1 and IL-8 release were significant up-regulated by TNF-α (ICAM-1) and by TNF-α and zymosan (IL-8), but not by pidotimod. In contrast, an increased TLR-2 expression was found after exposure to pidotimod 10 and 100 μg/ml (p < 0.05) and to the association pidotimod 100 μg/ml + TNF-α (p < 0.05). Western blot analysis substantiated that the constitutive TLR-2 expression was significantly increased after exposure to all the stimuli. Finally, while a remarkable inhibition of TNF-α -induced ERK1/2 phosphorylation was observed in the presence of pidotimod, both TNF-α and pidotimod were effective in inducing NF-kB protein expression in the cytoplasm and its nuclear translocation. CONCLUSION: Through different effects on ERK1/2 and NF-kB, pidotimod was able to increase the expression of TLR-2 proteins, surface molecules involved in the initiation of the innate response to infectious stimuli. The lack of effect on ICAM-1 expression, the receptor for rhinovirus, and on IL-8 release, the potent chemotactic factor for neutrophils (that are already present in sites of infection), may represent protective functions. If confirmed in vivo, these activities may, at least in part, clarify the mechanism of action of this molecule at airway level.",2013 May 10,"['Carta, Sonia', 'Silvestri, Michela', 'Rossi, Giovanni A']",Ital J Pediatr,,,True
77c5a33cacec66e3eecf748902a04cd245df6e0f,PMC,TNF-α Acts as an Immunoregulator in the Mouse Brain by Reducing the Incidence of Severe Disease Following Japanese Encephalitis Virus Infection,http://dx.doi.org/10.1371/journal.pone.0071643,PMC3733918,23940775,CC BY,"Japanese encephalitis virus (JEV) causes acute central nervous system (CNS) disease in humans, in whom the clinical symptoms vary from febrile illness to meningitis and encephalitis. However, the mechanism of severe encephalitis has not been fully elucidated. In this study, using a mouse model, we investigated the pathogenetic mechanisms that correlate with fatal JEV infection. Following extraneural infection with the JaOArS982 strain of JEV, infected mice exhibited clinical signs ranging from mild to fatal outcome. Comparison of the pathogenetic response between severe and mild cases of JaOArS982-infected mice revealed increased levels of TNF-α in the brains of severe cases. However, unexpectedly, the mortality rate of TNF-α KO mice was significantly increased compared with that of WT mice, indicating that TNF-α plays a protective role against fatal infection. Interestingly, there were no significant differences of viral load in the CNS between WT and TNF-α KO mice. However, exaggerated inflammatory responses were observed in the CNS of TNF-α KO mice. Although these observations were also obtained in IL-10 KO mice, the mortality and enhanced inflammatory responses were more pronounced in TNF-α KO mice. Our findings therefore provide the first evidence that TNF-α has an immunoregulatory effect on pro-inflammatory cytokines in the CNS during JEV infection and consequently protects the animals from fatal disease. Thus, we propose that the increased level of TNF-α in severe cases was the result of severe disease, and secondly that immunopathological effects contribute to severe neuronal degeneration resulting in fatal disease. In future, further elucidation of the immunoregulatory mechanism of TNF-α will be an important priority to enable the development of effective treatment strategies for Japanese encephalitis.",2013 Aug 5,"['Hayasaka, Daisuke', 'Shirai, Kenji', 'Aoki, Kotaro', 'Nagata, Noriyo', 'Simantini, Dash Sima', 'Kitaura, Kazutaka', 'Takamatsu, Yuki', 'Gould, Ernest', 'Suzuki, Ryuji', 'Morita, Kouichi']",PLoS One,,,True
789ab4d7c1e859c96e68389e03290355c30a03a7,PMC,Identification of cellular proteome using two-dimensional difference gel electrophoresis in ST cells infected with transmissible gastroenteritis coronavirus,http://dx.doi.org/10.1186/1477-5956-11-31,PMC3734006,23855489,CC BY,"BACKGROUND: Transmissible gastroenteritis coronavirus (TGEV) is an enteropathogenic coronavirus that causes diarrhea in pigs, which is correlated with high morbidity and mortality in suckling piglets. Information remains limited about the comparative protein expression of host cells in response to TGEV infection. In this study, cellular protein response to TGEV infection in swine testes (ST) cells was analyzed, using the proteomic method of two-dimensional difference gel electrophoresis (2D DIGE) coupled with MALDI-TOF-TOF/MS identification. RESULTS: 33 differentially expressed protein spots, of which 23 were up-regulated and 10 were down-regulated were identified. All the protein spots were successfully identified. The identified proteins were involved in the regulation of essential processes such as cellular structure and integrity, RNA processing, protein biosynthesis and modification, vesicle transport, signal transduction, and the mitochondrial pathway. Western blot analysis was used to validate the changes of alpha tubulin, keratin 19, and prohibitin during TGEV infection. CONCLUSIONS: To our knowledge, we have performed the first analysis of the proteomic changes in host cell during TGEV infection. 17 altered cellular proteins that differentially expressed in TGEV infection were identified. The present study provides protein-related information that should be useful for understanding the host cell response to TGEV infection and the underlying mechanism of TGEV replication and pathogenicity.",2013 Jul 16,"['Zhang, Xin', 'Shi, Hong-Yan', 'Chen, Jian-Fei', 'Shi, Da', 'Lang, Hong-Wu', 'Wang, Zhong-Tian', 'Feng, Li']",Proteome Sci,,,True
ee8483f8f2cc5fe38be4e565eae3af9d0bb8220b,PMC,"Design, Synthesis, Evaluation and Thermodynamics of 1-Substituted Pyridylimidazo[1,5-a]Pyridine Derivatives as Cysteine Protease Inhibitors",http://dx.doi.org/10.1371/journal.pone.0069982,PMC3734177,23940536,CC BY,"Targeting papain family cysteine proteases is one of the novel strategies in the development of chemotherapy for a number of diseases. Novel cysteine protease inhibitors derived from 1-pyridylimidazo[1,5-a]pyridine representing pharmacologically important class of compounds are being reported here for the first time. The derivatives were initially designed and screened in silico by molecular docking studies against papain to explore the possible mode of action. The molecular interaction between the compounds and cysteine protease (papain) was found to be very similar to the interactions observed with the respective epoxide inhibitor (E-64c) of papain. Subsequently, compounds were synthesized to validate their efficacy in wet lab experiments. When characterized kinetically, these compounds show their K(i) and IC(50) values in the range of 13.75 to 99.30 µM and 13.40 to 96.50 µM, respectively. The thermodynamics studies suggest their binding with papain hydrophobically and entropically driven. These inhibitors also inhibit the growth of clinically important different types of Gram positive and Gram negative bacteria having MIC(50) values in the range of 0.6–1.4 µg/ml. Based on Lipinski’s rule of Five, we also propose these compounds as potent antibacterial prodrugs. The most active antibacterial compound was found to be 1-(2-pyridyl)-3-(2-hydroxyphenyl)imidazo[1,5-a]pyridine (3a).",2013 Aug 5,"['Khan, Mohd Sajid', 'Baig, Mohd Hassan', 'Ahmad, Saheem', 'Siddiqui, Shapi Ahmad', 'Srivastava, Ashwini Kumar', 'Srinivasan, Kumar Venkatraman', 'Ansari, Irfan A.']",PLoS One,,,True
5314aaa04b14fdbb926bc8eeb0826eedee66dadc,PMC,Understanding and Managing Zoonotic Risk in the New Livestock Industries,http://dx.doi.org/10.1289/ehp.1206001,PMC3734490,23665854,CC0,"Background: In many parts of the world, livestock production is undergoing a process of rapid intensification. The health implications of this development are uncertain. Intensification creates cheaper products, allowing more people to access animal-based foods. However, some practices associated with intensification may contribute to zoonotic disease emergence and spread: for example, the sustained use of antibiotics, concentration of animals in confined units, and long distances and frequent movement of livestock. Objectives: Here we present the diverse range of ecological, biological, and socioeconomic factors likely to enhance or reduce zoonotic risk, and identify ways in which a comprehensive risk analysis may be conducted by using an interdisciplinary approach. We also offer a conceptual framework to guide systematic research on this problem. Discussion: We recommend that interdisciplinary work on zoonotic risk should take into account the complexity of risk environments, rather than limiting studies to simple linear causal relations between risk drivers and disease emergence and/or spread. In addition, interdisciplinary integration is needed at different levels of analysis, from the study of risk environments to the identification of policy options for risk management. Conclusion: Given rapid changes in livestock production systems and their potential health implications at the local and global level, the problem we analyze here is of great importance for environmental health and development. Although we offer a systematic interdisciplinary approach to understand and address these implications, we recognize that further research is needed to clarify methodological and practical questions arising from the integration of the natural and social sciences.",2013 Aug 10,"['Liverani, Marco', 'Waage, Jeff', 'Barnett, Tony', 'Pfeiffer, Dirk U.', 'Rushton, Jonathan', 'Rudge, James W.', 'Loevinsohn, Michael E.', 'Scoones, Ian', 'Smith, Richard D.', 'Cooper, Ben S.', 'White, Lisa J.', 'Goh, Shan', 'Horby, Peter', 'Wren, Brendan', 'Gundogdu, Ozan', 'Woods, Abigail', 'Coker, Richard J.']",Environ Health Perspect,,,True
09561ed721369a7a9e077f7bea9022499c12b13d,PMC,Estimating the reproductive number in the presence of spatial heterogeneity of transmission patterns,http://dx.doi.org/10.1186/1476-072X-12-35,PMC3735474,23890514,CC BY,"BACKGROUND: Estimates of parameters for disease transmission in large-scale infectious disease outbreaks are often obtained to represent large groups of people, providing an average over a potentially very diverse area. For control measures to be more effective, a measure of the heterogeneity of the parameters is desirable. METHODS: We propose a novel extension of a network-based approach to estimating the reproductive number. With this we can incorporate spatial and/or demographic information through a similarity matrix. We apply this to the 2009 Influenza pandemic in South Africa to understand the spatial variability across provinces. We explore the use of five similarity matrices to illustrate their impact on the subsequent epidemic parameter estimates. RESULTS: When treating South Africa as a single entity with homogeneous transmission characteristics across the country, the basic reproductive number, R(0), (and imputation range) is 1.33 (1.31, 1.36). When fitting a new model for each province with no inter-province connections this estimate varies little (1.23-1.37). Using the proposed method with any of the four similarity measures yields an overall R(0) that varies little across the four new models (1.33 to 1.34). However, when allowed to vary across provinces, the estimated R(0) is greater than one consistently in only two of the nine provinces, the most densely populated provinces of Gauteng and Western Cape. CONCLUSIONS: Our results suggest that the spatial heterogeneity of influenza transmission was compelling in South Africa during the 2009 pandemic. This variability makes a qualitative difference in our understanding of the epidemic. While the cause of this fluctuation might be partially due to reporting differences, there is substantial evidence to warrant further investigation.",2013 Jul 26,"['White, Laura F', 'Archer, Brett', 'Pagano, Marcello']",Int J Health Geogr,,,True
ea2a30291a27a30b944a84050fff8bdf64e94130,PMC,Smallpox Still Haunts Scientists: Results of a Questionnaire-Based Inquiry on the Views of Health Care and Life Science Experts and Students on Preserving the Remaining Variola Virus Stocks,http://dx.doi.org/10.1155/2013/672813,PMC3736420,23970838,CC BY,"The World Health Organization (WHO) declared eradication of the dreadful disease “smallpox” in 1980. Though the disease has died down, the causative virus “variola” has not, as it has been well preserved in two high security laboratories—one in USA and another in Russia. The debate on whether the remaining stocks of the smallpox virus should be destroyed or not is ongoing, and the World Health Assembly (WHA) in 2011 has decided to postpone the review on this debate to the 67th WHA in 2014. A short questionnaire-based inquiry was organized during a one-day stem cell meeting to explore the views of various health care and life science specialists especially students on this aspect. Among the 200 participants of the meeting, only 66 had answered the questionnaire. 60.6% of participants who responded to the questionnaire were for preserving the virus for future reference, while 36.4% of the participants were for destroying the virus considering the magnitude with which it killed millions. However, 3% of the respondents were not able to decide on any verdict. Therefore, this inquiry expresses the view that “what we cannot create, we do not have the right to destroy.”",2013 Jul 22,"['Srinivasan, Thangavelu', 'Dedeepiya, Vidyasagar Devaprasad', 'John, Sudhakar', 'Senthilkumar, Rajappa', 'Reena, Helen C.', 'Rajendran, Paramasivam', 'Balamurugan, Madasamy', 'Kurosawa, Gene', 'Iwasaki, Masaru', 'Preethy, Senthilkumar', 'Abraham, Samuel J. K.']",ScientificWorldJournal,,,True
a7344a564121bf1e3f995911e78c17b1b2aee903,PMC,A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication,http://dx.doi.org/10.1371/journal.ppat.1003514,PMC3738494,23950709,CC BY,"Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome.",2013 Aug 8,"['Griffiths, Samantha J.', 'Koegl, Manfred', 'Boutell, Chris', 'Zenner, Helen L.', 'Crump, Colin M.', 'Pica, Francesca', 'Gonzalez, Orland', 'Friedel, Caroline C.', 'Barry, Gerald', 'Martin, Kim', 'Craigon, Marie H.', 'Chen, Rui', 'Kaza, Lakshmi N.', 'Fossum, Even', 'Fazakerley, John K.', 'Efstathiou, Stacey', 'Volpi, Antonio', 'Zimmer, Ralf', 'Ghazal, Peter', 'Haas, Jürgen']",PLoS Pathog,,,True
da309b7481a117d1aad2212d42ad3b7c0c68abf3,PMC,Crystal Structure of the Full-Length Japanese Encephalitis Virus NS5 Reveals a Conserved Methyltransferase-Polymerase Interface,http://dx.doi.org/10.1371/journal.ppat.1003549,PMC3738499,23950717,CC BY,"The flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. The structure completes the vision for polymerase motifs F and G, and depicts defined intra-molecular interactions between RdRP and MTase. Key hydrophobic residues in the RdRP-MTase interface are highly conserved in flaviviruses, indicating the biological relevance of the observed conformation. Our work paves the way for further dissection of the inter-regulations of the essential enzymatic activities of NS5 and exploration of possible other conformations of NS5 under different circumstances.",2013 Aug 8,"['Lu, Guoliang', 'Gong, Peng']",PLoS Pathog,,,True
2d1c0935153f0c1139529c1c05373504028abd4a,PMC,Crystal Structure of the Full-Length Japanese Encephalitis Virus NS5 Reveals a Conserved Methyltransferase-Polymerase Interface,http://dx.doi.org/10.1371/journal.ppat.1003549,PMC3738499,23950717,CC BY,"The flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. The structure completes the vision for polymerase motifs F and G, and depicts defined intra-molecular interactions between RdRP and MTase. Key hydrophobic residues in the RdRP-MTase interface are highly conserved in flaviviruses, indicating the biological relevance of the observed conformation. Our work paves the way for further dissection of the inter-regulations of the essential enzymatic activities of NS5 and exploration of possible other conformations of NS5 under different circumstances.",2013 Aug 8,"['Lu, Guoliang', 'Gong, Peng']",PLoS Pathog,,,True
7763fdd2366c612dc01aaf0173ea6bb8f1ed0bf9,PMC,Complete Genome Sequence of Porcine Epidemic Diarrhea Virus Strain USA/Colorado/2013 from the United States,http://dx.doi.org/10.1128/genomeA.00555-13,PMC3738886,23929470,CC BY,"Porcine epidemic diarrhea virus (PEDV) is newly emerging in the United States. PEDV strain USA/Colorado/2013 (CO/13) was obtained from a 7-day-old piglet with severe diarrhea, and the complete genome was sequenced to further study the PEDV outbreak in the United States.",2013 Aug 8,"['Marthaler, Douglas', 'Jiang, Yin', 'Otterson, Tracy', 'Goyal, Sagar', 'Rossow, Kurt', 'Collins, James']",Genome Announc,,,True
33542ce3cc964e6621e0ce35fedd41b34367de76,PMC,Histone Deacetylases in Herpesvirus Replication and Virus-Stimulated Host Defense,http://dx.doi.org/10.3390/v5071607,PMC3738950,23807710,CC BY,"Emerging evidence highlights a critical role for protein acetylation during herpesvirus infection. As prominent modulators of protein acetylation, histone deacetylases (HDACs) are essential transcriptional and epigenetic regulators. Not surprisingly, viruses have evolved a wide array of mechanisms to subvert HDAC functions. Here, we review the mechanisms underlying HDAC regulation during herpesvirus infection. We next discuss the roles of acetylation in host defense against herpesvirus infection. Finally, we provide a perspective on the contribution of current mass spectrometry-based “omic” technologies to infectious disease research, offering a systems biology view of infection.",2013 Jun 27,"['Guise, Amanda J.', 'Budayeva, Hanna G.', 'Diner, Benjamin A.', 'Cristea, Ileana M.']",Viruses,,,True
860ddc48c73d4757ceb161a9b43e73138b6b94a4,PMC,Cyclophilins as Modulators of Viral Replication,http://dx.doi.org/10.3390/v5071684,PMC3738956,23852270,CC BY,"Cyclophilins are peptidyl‐prolyl cis/trans isomerases important in the proper folding of certain proteins. Mounting evidence supports varied roles of cyclophilins, either positive or negative, in the life cycles of diverse viruses, but the nature and mechanisms of these roles are yet to be defined. The potential for cyclophilins to serve as a drug target for antiviral therapy is evidenced by the success of non-immunosuppressive cyclophilin inhibitors (CPIs), including Alisporivir, in clinical trials targeting hepatitis C virus infection. In addition, as cyclophilins are implicated in the predisposition to, or severity of, various diseases, the ability to specifically and effectively modulate their function will prove increasingly useful for disease intervention. In this review, we will summarize the evidence of cyclophilins as key mediators of viral infection and prospective drug targets.",2013 Jul 11,"['Frausto, Stephen D.', 'Lee, Emily', 'Tang, Hengli']",Viruses,,,True
a50f42269649e20ec3580496c72923ef1c4abd6a,PMC,Genomic and Proteomic Analysis of Schizaphis graminum Reveals Cyclophilin Proteins Are Involved in the Transmission of Cereal Yellow Dwarf Virus,http://dx.doi.org/10.1371/journal.pone.0071620,PMC3739738,23951206,CC0,"Yellow dwarf viruses cause the most economically important virus diseases of cereal crops worldwide and are transmitted by aphid vectors. The identification of aphid genes and proteins mediating virus transmission is critical to develop agriculturally sustainable virus management practices and to understand viral strategies for circulative movement in all insect vectors. Two cyclophilin B proteins, S28 and S29, were identified previously in populations of Schizaphisgraminum that differed in their ability to transmit the RPV strain of Cereal yellow dwarf virus (CYDV-RPV). The presence of S29 was correlated with F2 genotypes that were efficient virus transmitters. The present study revealed the two proteins were isoforms, and a single amino acid change distinguished S28 and S29. The distribution of the two alleles was determined in 12 F2 genotypes segregating for CYDV-RPV transmission capacity and in 11 genetically independent, field-collected S . graminum biotypes. Transmission efficiency for CYDV-RPV was determined in all genotypes and biotypes. The S29 isoform was present in all genotypes or biotypes that efficiently transmit CYDV-RPV and more specifically in genotypes that efficiently transport virus across the hindgut. We confirmed a direct interaction between CYDV-RPV and both S28 and S29 using purified virus and bacterially expressed, his-tagged S28 and S29 proteins. Importantly, S29 failed to interact with a closely related virus that is transported across the aphid midgut. We tested for in vivo interactions using an aphid-virus co-immunoprecipitation strategy coupled with a bottom-up LC-MS/MS analysis using a Q Exactive mass spectrometer. This analysis enabled us to identify a third cyclophilin protein, cyclophilin A, interacting directly or in complex with purified CYDV-RPV. Taken together, these data provide evidence that both cyclophilin A and B interact with CYDV-RPV, and these interactions may be important but not sufficient to mediate virus transport from the hindgut lumen into the hemocoel.",2013 Aug 9,"['Tamborindeguy, Cecilia', 'Bereman, Michael S.', 'DeBlasio, Stacy', 'Igwe, David', 'Smith, Dawn M.', 'White, Frank', 'MacCoss, Michael J.', 'Gray, Stewart M.', 'Cilia, Michelle']",PLoS One,,,True
7806d17eeaae9415e597155236a28b9ca9cba137,PMC,Genomic and Proteomic Analysis of Schizaphis graminum Reveals Cyclophilin Proteins Are Involved in the Transmission of Cereal Yellow Dwarf Virus,http://dx.doi.org/10.1371/journal.pone.0071620,PMC3739738,23951206,CC0,"Yellow dwarf viruses cause the most economically important virus diseases of cereal crops worldwide and are transmitted by aphid vectors. The identification of aphid genes and proteins mediating virus transmission is critical to develop agriculturally sustainable virus management practices and to understand viral strategies for circulative movement in all insect vectors. Two cyclophilin B proteins, S28 and S29, were identified previously in populations of Schizaphisgraminum that differed in their ability to transmit the RPV strain of Cereal yellow dwarf virus (CYDV-RPV). The presence of S29 was correlated with F2 genotypes that were efficient virus transmitters. The present study revealed the two proteins were isoforms, and a single amino acid change distinguished S28 and S29. The distribution of the two alleles was determined in 12 F2 genotypes segregating for CYDV-RPV transmission capacity and in 11 genetically independent, field-collected S . graminum biotypes. Transmission efficiency for CYDV-RPV was determined in all genotypes and biotypes. The S29 isoform was present in all genotypes or biotypes that efficiently transmit CYDV-RPV and more specifically in genotypes that efficiently transport virus across the hindgut. We confirmed a direct interaction between CYDV-RPV and both S28 and S29 using purified virus and bacterially expressed, his-tagged S28 and S29 proteins. Importantly, S29 failed to interact with a closely related virus that is transported across the aphid midgut. We tested for in vivo interactions using an aphid-virus co-immunoprecipitation strategy coupled with a bottom-up LC-MS/MS analysis using a Q Exactive mass spectrometer. This analysis enabled us to identify a third cyclophilin protein, cyclophilin A, interacting directly or in complex with purified CYDV-RPV. Taken together, these data provide evidence that both cyclophilin A and B interact with CYDV-RPV, and these interactions may be important but not sufficient to mediate virus transport from the hindgut lumen into the hemocoel.",2013 Aug 9,"['Tamborindeguy, Cecilia', 'Bereman, Michael S.', 'DeBlasio, Stacy', 'Igwe, David', 'Smith, Dawn M.', 'White, Frank', 'MacCoss, Michael J.', 'Gray, Stewart M.', 'Cilia, Michelle']",PLoS One,,,False
b3296f06a1c5c437d06d40c987ef2f13f4b35d59,PMC,Genomic and Proteomic Analysis of Schizaphis graminum Reveals Cyclophilin Proteins Are Involved in the Transmission of Cereal Yellow Dwarf Virus,http://dx.doi.org/10.1371/journal.pone.0071620,PMC3739738,23951206,CC0,"Yellow dwarf viruses cause the most economically important virus diseases of cereal crops worldwide and are transmitted by aphid vectors. The identification of aphid genes and proteins mediating virus transmission is critical to develop agriculturally sustainable virus management practices and to understand viral strategies for circulative movement in all insect vectors. Two cyclophilin B proteins, S28 and S29, were identified previously in populations of Schizaphisgraminum that differed in their ability to transmit the RPV strain of Cereal yellow dwarf virus (CYDV-RPV). The presence of S29 was correlated with F2 genotypes that were efficient virus transmitters. The present study revealed the two proteins were isoforms, and a single amino acid change distinguished S28 and S29. The distribution of the two alleles was determined in 12 F2 genotypes segregating for CYDV-RPV transmission capacity and in 11 genetically independent, field-collected S . graminum biotypes. Transmission efficiency for CYDV-RPV was determined in all genotypes and biotypes. The S29 isoform was present in all genotypes or biotypes that efficiently transmit CYDV-RPV and more specifically in genotypes that efficiently transport virus across the hindgut. We confirmed a direct interaction between CYDV-RPV and both S28 and S29 using purified virus and bacterially expressed, his-tagged S28 and S29 proteins. Importantly, S29 failed to interact with a closely related virus that is transported across the aphid midgut. We tested for in vivo interactions using an aphid-virus co-immunoprecipitation strategy coupled with a bottom-up LC-MS/MS analysis using a Q Exactive mass spectrometer. This analysis enabled us to identify a third cyclophilin protein, cyclophilin A, interacting directly or in complex with purified CYDV-RPV. Taken together, these data provide evidence that both cyclophilin A and B interact with CYDV-RPV, and these interactions may be important but not sufficient to mediate virus transport from the hindgut lumen into the hemocoel.",2013 Aug 9,"['Tamborindeguy, Cecilia', 'Bereman, Michael S.', 'DeBlasio, Stacy', 'Igwe, David', 'Smith, Dawn M.', 'White, Frank', 'MacCoss, Michael J.', 'Gray, Stewart M.', 'Cilia, Michelle']",PLoS One,,,False
adf74045a387615c92918b078dd360d66d64faea,PMC,Genomic and Proteomic Analysis of Schizaphis graminum Reveals Cyclophilin Proteins Are Involved in the Transmission of Cereal Yellow Dwarf Virus,http://dx.doi.org/10.1371/journal.pone.0071620,PMC3739738,23951206,CC0,"Yellow dwarf viruses cause the most economically important virus diseases of cereal crops worldwide and are transmitted by aphid vectors. The identification of aphid genes and proteins mediating virus transmission is critical to develop agriculturally sustainable virus management practices and to understand viral strategies for circulative movement in all insect vectors. Two cyclophilin B proteins, S28 and S29, were identified previously in populations of Schizaphisgraminum that differed in their ability to transmit the RPV strain of Cereal yellow dwarf virus (CYDV-RPV). The presence of S29 was correlated with F2 genotypes that were efficient virus transmitters. The present study revealed the two proteins were isoforms, and a single amino acid change distinguished S28 and S29. The distribution of the two alleles was determined in 12 F2 genotypes segregating for CYDV-RPV transmission capacity and in 11 genetically independent, field-collected S . graminum biotypes. Transmission efficiency for CYDV-RPV was determined in all genotypes and biotypes. The S29 isoform was present in all genotypes or biotypes that efficiently transmit CYDV-RPV and more specifically in genotypes that efficiently transport virus across the hindgut. We confirmed a direct interaction between CYDV-RPV and both S28 and S29 using purified virus and bacterially expressed, his-tagged S28 and S29 proteins. Importantly, S29 failed to interact with a closely related virus that is transported across the aphid midgut. We tested for in vivo interactions using an aphid-virus co-immunoprecipitation strategy coupled with a bottom-up LC-MS/MS analysis using a Q Exactive mass spectrometer. This analysis enabled us to identify a third cyclophilin protein, cyclophilin A, interacting directly or in complex with purified CYDV-RPV. Taken together, these data provide evidence that both cyclophilin A and B interact with CYDV-RPV, and these interactions may be important but not sufficient to mediate virus transport from the hindgut lumen into the hemocoel.",2013 Aug 9,"['Tamborindeguy, Cecilia', 'Bereman, Michael S.', 'DeBlasio, Stacy', 'Igwe, David', 'Smith, Dawn M.', 'White, Frank', 'MacCoss, Michael J.', 'Gray, Stewart M.', 'Cilia, Michelle']",PLoS One,,,False
a77ae8185b435c1d841766ba9d031bab9366b7bd,PMC,Genomic and Proteomic Analysis of Schizaphis graminum Reveals Cyclophilin Proteins Are Involved in the Transmission of Cereal Yellow Dwarf Virus,http://dx.doi.org/10.1371/journal.pone.0071620,PMC3739738,23951206,CC0,"Yellow dwarf viruses cause the most economically important virus diseases of cereal crops worldwide and are transmitted by aphid vectors. The identification of aphid genes and proteins mediating virus transmission is critical to develop agriculturally sustainable virus management practices and to understand viral strategies for circulative movement in all insect vectors. Two cyclophilin B proteins, S28 and S29, were identified previously in populations of Schizaphisgraminum that differed in their ability to transmit the RPV strain of Cereal yellow dwarf virus (CYDV-RPV). The presence of S29 was correlated with F2 genotypes that were efficient virus transmitters. The present study revealed the two proteins were isoforms, and a single amino acid change distinguished S28 and S29. The distribution of the two alleles was determined in 12 F2 genotypes segregating for CYDV-RPV transmission capacity and in 11 genetically independent, field-collected S . graminum biotypes. Transmission efficiency for CYDV-RPV was determined in all genotypes and biotypes. The S29 isoform was present in all genotypes or biotypes that efficiently transmit CYDV-RPV and more specifically in genotypes that efficiently transport virus across the hindgut. We confirmed a direct interaction between CYDV-RPV and both S28 and S29 using purified virus and bacterially expressed, his-tagged S28 and S29 proteins. Importantly, S29 failed to interact with a closely related virus that is transported across the aphid midgut. We tested for in vivo interactions using an aphid-virus co-immunoprecipitation strategy coupled with a bottom-up LC-MS/MS analysis using a Q Exactive mass spectrometer. This analysis enabled us to identify a third cyclophilin protein, cyclophilin A, interacting directly or in complex with purified CYDV-RPV. Taken together, these data provide evidence that both cyclophilin A and B interact with CYDV-RPV, and these interactions may be important but not sufficient to mediate virus transport from the hindgut lumen into the hemocoel.",2013 Aug 9,"['Tamborindeguy, Cecilia', 'Bereman, Michael S.', 'DeBlasio, Stacy', 'Igwe, David', 'Smith, Dawn M.', 'White, Frank', 'MacCoss, Michael J.', 'Gray, Stewart M.', 'Cilia, Michelle']",PLoS One,,,False
896d8340cfc2185b9ba57fa6d3f3b6e93824bac0,PMC,Genomic and Proteomic Analysis of Schizaphis graminum Reveals Cyclophilin Proteins Are Involved in the Transmission of Cereal Yellow Dwarf Virus,http://dx.doi.org/10.1371/journal.pone.0071620,PMC3739738,23951206,CC0,"Yellow dwarf viruses cause the most economically important virus diseases of cereal crops worldwide and are transmitted by aphid vectors. The identification of aphid genes and proteins mediating virus transmission is critical to develop agriculturally sustainable virus management practices and to understand viral strategies for circulative movement in all insect vectors. Two cyclophilin B proteins, S28 and S29, were identified previously in populations of Schizaphisgraminum that differed in their ability to transmit the RPV strain of Cereal yellow dwarf virus (CYDV-RPV). The presence of S29 was correlated with F2 genotypes that were efficient virus transmitters. The present study revealed the two proteins were isoforms, and a single amino acid change distinguished S28 and S29. The distribution of the two alleles was determined in 12 F2 genotypes segregating for CYDV-RPV transmission capacity and in 11 genetically independent, field-collected S . graminum biotypes. Transmission efficiency for CYDV-RPV was determined in all genotypes and biotypes. The S29 isoform was present in all genotypes or biotypes that efficiently transmit CYDV-RPV and more specifically in genotypes that efficiently transport virus across the hindgut. We confirmed a direct interaction between CYDV-RPV and both S28 and S29 using purified virus and bacterially expressed, his-tagged S28 and S29 proteins. Importantly, S29 failed to interact with a closely related virus that is transported across the aphid midgut. We tested for in vivo interactions using an aphid-virus co-immunoprecipitation strategy coupled with a bottom-up LC-MS/MS analysis using a Q Exactive mass spectrometer. This analysis enabled us to identify a third cyclophilin protein, cyclophilin A, interacting directly or in complex with purified CYDV-RPV. Taken together, these data provide evidence that both cyclophilin A and B interact with CYDV-RPV, and these interactions may be important but not sufficient to mediate virus transport from the hindgut lumen into the hemocoel.",2013 Aug 9,"['Tamborindeguy, Cecilia', 'Bereman, Michael S.', 'DeBlasio, Stacy', 'Igwe, David', 'Smith, Dawn M.', 'White, Frank', 'MacCoss, Michael J.', 'Gray, Stewart M.', 'Cilia, Michelle']",PLoS One,,,False
4551a670ee8751ea93b9c5e01ea9ac30fde7ab03,PMC,Economic and Environmental Impacts of Harmful Non-Indigenous Species in Southeast Asia,http://dx.doi.org/10.1371/journal.pone.0071255,PMC3739798,23951120,CC BY,"Harmful non-indigenous species (NIS) impose great economic and environmental impacts globally, but little is known about their impacts in Southeast Asia. Lack of knowledge of the magnitude of the problem hinders the allocation of appropriate resources for NIS prevention and management. We used benefit-cost analysis embedded in a Monte-Carlo simulation model and analysed economic and environmental impacts of NIS in the region to estimate the total burden of NIS in Southeast Asia. The total annual loss caused by NIS to agriculture, human health and the environment in Southeast Asia is estimated to be US$33.5 billion (5(th) and 95(th) percentile US$25.8–39.8 billion). Losses and costs to the agricultural sector are estimated to be nearly 90% of the total (US$23.4–33.9 billion), while the annual costs associated with human health and the environment are US$1.85 billion (US$1.4–2.5 billion) and US$2.1 billion (US$0.9–3.3 billion), respectively, although these estimates are based on conservative assumptions. We demonstrate that the economic and environmental impacts of NIS in low and middle-income regions can be considerable and that further measures, such as the adoption of regional risk assessment protocols to inform decisions on prevention and control of NIS in Southeast Asia, could be beneficial.",2013 Aug 9,"['Nghiem, Le T. P.', 'Soliman, Tarek', 'Yeo, Darren C. J.', 'Tan, Hugh T. W.', 'Evans, Theodore A.', 'Mumford, John D.', 'Keller, Reuben P.', 'Baker, Richard H. A.', 'Corlett, Richard T.', 'Carrasco, Luis R.']",PLoS One,,,True
33ea5a062d23a8c46b7d6e9ba23f1c82f40fde29,PMC,Discovery of a Bovine Enterovirus in Alpaca,http://dx.doi.org/10.1371/journal.pone.0068777,PMC3741315,23950875,CC0,"A cytopathic virus was isolated using Madin-Darby bovine kidney (MDBK) cells from lung tissue of alpaca that died of a severe respiratory infection. To identify the virus, the infected cell culture supernatant was enriched for virus particles and a generic, PCR-based method was used to amplify potential viral sequences. Genomic sequence data of the alpaca isolate was obtained and compared with sequences of known viruses. The new alpaca virus sequence was most similar to recently designated Enterovirus species F, previously bovine enterovirus (BEVs), viruses that are globally prevalent in cattle, although they appear not to cause significant disease. Because bovine enteroviruses have not been previously reported in U.S. alpaca, we suspect that this type of infection is fairly rare, and in this case appeared not to spread beyond the original outbreak. The capsid sequence of the detected virus had greatest homology to Enterovirus F type 1 (indicating that the virus should be considered a member of serotype 1), but the virus had greater homology in 2A protease sequence to type 3, suggesting that it may have been a recombinant. Identifying pathogens that infect a new host species for the first time can be challenging. As the disease in a new host species may be quite different from that in the original or natural host, the pathogen may not be suspected based on the clinical presentation, delaying diagnosis. Although this virus replicated in MDBK cells, existing standard culture and molecular methods could not identify it. In this case, a highly sensitive generic PCR-based pathogen-detection method was used to identify this pathogen.",2013 Aug 12,"['McClenahan, Shasta D.', 'Scherba, Gail', 'Borst, Luke', 'Fredrickson, Richard L.', 'Krause, Philip R.', 'Uhlenhaut, Christine']",PLoS One,,,True
c61f5c4971f07156d3c1d9dd76de4b158855ecc1,PMC,A Protective and Safe Intranasal RSV Vaccine Based on a Recombinant Prefusion-Like Form of the F Protein Bound to Bacterium-Like Particles,http://dx.doi.org/10.1371/journal.pone.0071072,PMC3741363,23951084,CC BY,"Respiratory syncytial virus (RSV) is an important cause of respiratory tract disease in infants and the elderly. Currently, no licensed vaccine against RSV is available. Here we describe the development of a safe and effective intranasal subunit vaccine that is based on recombinant fusion (F) protein bound to the surface of immunostimulatory bacterium-like particles (BLPs) derived from the food-grade bacterium Lactococcus lactis. Different variants of F were analyzed with respect to their conformation and reactivity with neutralizing antibodies, assuming that F proteins mimicking the metastable prefusion form of RSV F expose a more extensive and relevant epitope repertoire than F proteins corresponding to the postfusion structure. Our results indicate that the recombinant soluble ectodomain of RSV F readily adopts a postfusion conformation, generation of which cannot be prevented by C-terminal addition of a trimerization motif, but whose formation is prevented by mutation of the two furin cleavage sites in F. While the putative postfusion form of F is recognized well by the monoclonal antibody Palivizumab, this is much less so for the more potently neutralizing, prefusion-specific antibodies D25 and AM22. Both addition of the trimerization motif and mutation of the furin cleavage sites increased the reactivity of F with D25 and AM22, with the highest reactivity being observed for F proteins in which both these features were combined. Intranasal vaccination of mice or cotton rats with BLPs loaded with this latter prefusion-like F protein (BLP-F), resulted in the potent induction of F-specific immunoglobulins and in significantly decreased virus titers in the lungs upon RSV challenge. Moreover, and in contrast to animals vaccinated with formalin-inactivated RSV, animals that received BLP-F exhibited high levels of F-specific secretory IgA in the nose and RSV-neutralizing antibodies in sera, but did not show symptoms of enhanced disease after challenge with RSV.",2013 Aug 12,"['Rigter, Alan', 'Widjaja, Ivy', 'Versantvoort, Hanneke', 'Coenjaerts, Frank E. J.', 'van Roosmalen, Maarten', 'Leenhouts, Kees', 'Rottier, Peter J. M.', 'Haijema, Bert Jan', 'de Haan, Cornelis A. M.']",PLoS One,,,True
a4e2f812c3232e60ac1af78fed10d292e28906d1,PMC,Using the Electronic Medical Record to Identify Community-Acquired Pneumonia: Toward a Replicable Automated Strategy,http://dx.doi.org/10.1371/journal.pone.0070944,PMC3742728,23967138,CC0,"BACKGROUND: Timely information about disease severity can be central to the detection and management of outbreaks of acute respiratory infections (ARI), including influenza. We asked if two resources: 1) free text, and 2) structured data from an electronic medical record (EMR) could complement each other to identify patients with pneumonia, an ARI severity landmark. METHODS: A manual EMR review of 2747 outpatient ARI visits with associated chest imaging identified x-ray reports that could support the diagnosis of pneumonia (kappa score = 0.88 (95% CI 0.82∶0.93)), along with attendant cases with Possible Pneumonia (adds either cough, sputum, fever/chills/night sweats, dyspnea or pleuritic chest pain) or with Pneumonia-in-Plan (adds pneumonia stated as a likely diagnosis by the provider). The x-ray reports served as a reference to develop a text classifier using machine-learning software that did not require custom coding. To identify pneumonia cases, the classifier was combined with EMR-based structured data and with text analyses aimed at ARI symptoms in clinical notes. RESULTS: 370 reference cases with Possible Pneumonia and 250 with Pneumonia-in-Plan were identified. The x-ray report text classifier increased the positive predictive value of otherwise identical EMR-based case-detection algorithms by 20–70%, while retaining sensitivities of 58–75%. These performance gains were independent of the case definitions and of whether patients were admitted to the hospital or sent home. Text analyses seeking ARI symptoms in clinical notes did not add further value. CONCLUSION: Specialized software development is not required for automated text analyses to help identify pneumonia patients. These results begin to map an efficient, replicable strategy through which EMR data can be used to stratify ARI severity.",2013 Aug 13,"['DeLisle, Sylvain', 'Kim, Bernard', 'Deepak, Janaki', 'Siddiqui, Tariq', 'Gundlapalli, Adi', 'Samore, Matthew', ""D'Avolio, Leonard""]",PLoS One,,,True
3ae4cc1c1b639a21e95972d63cfe5822b96d136d,PMC,Hazard Analysis of Critical Control Points Assessment as a Tool to Respond to Emerging Infectious Disease Outbreaks,http://dx.doi.org/10.1371/journal.pone.0072279,PMC3743774,23967294,CC BY,"Highly pathogenic avian influenza virus (HPAI) strain H5N1 has had direct and indirect economic impacts arising from direct mortality and control programmes in over 50 countries reporting poultry outbreaks. HPAI H5N1 is now reported as the most widespread and expensive zoonotic disease recorded and continues to pose a global health threat. The aim of this research was to assess the potential of utilising Hazard Analysis of Critical Control Points (HACCP) assessments in providing a framework for a rapid response to emerging infectious disease outbreaks. This novel approach applies a scientific process, widely used in food production systems, to assess risks related to a specific emerging health threat within a known zoonotic disease hotspot. We conducted a HACCP assessment for HPAI viruses within Vietnam’s domestic poultry trade and relate our findings to the existing literature. Our HACCP assessment identified poultry flock isolation, transportation, slaughter, preparation and consumption as critical control points for Vietnam’s domestic poultry trade. Introduction of the preventative measures highlighted through this HACCP evaluation would reduce the risks posed by HPAI viruses and pressure on the national economy. We conclude that this HACCP assessment provides compelling evidence for the future potential that HACCP analyses could play in initiating a rapid response to emerging infectious diseases.",2013 Aug 14,"['Edmunds, Kelly L.', 'Hunter, Paul R.', 'Few, Roger', 'Bell, Diana J.']",PLoS One,,,True
6f779376c8f76658fa6ab19c24748a56ee00aa49,PMC,A Compact Viral Processing Proteinase/Ubiquitin Hydrolase from the OTU Family,http://dx.doi.org/10.1371/journal.ppat.1003560,PMC3744425,23966860,CC BY,"Turnip yellow mosaic virus (TYMV) - a member of the alphavirus-like supergroup of viruses - serves as a model system for positive-stranded RNA virus membrane-bound replication. TYMV encodes a precursor replication polyprotein that is processed by the endoproteolytic activity of its internal cysteine proteinase domain (PRO). We recently reported that PRO is actually a multifunctional enzyme with a specific ubiquitin hydrolase (DUB) activity that contributes to viral infectivity. Here, we report the crystal structure of the 150-residue PRO. Strikingly, PRO displays no homology to other processing proteinases from positive-stranded RNA viruses, including that of alphaviruses. Instead, the closest structural homologs of PRO are DUBs from the Ovarian tumor (OTU) family. In the crystal, one molecule's C-terminus inserts into the catalytic cleft of the next, providing a view of the N-terminal product complex in replication polyprotein processing. This allows us to locate the specificity determinants of PRO for its proteinase substrates. In addition to the catalytic cleft, at the exit of which the active site is unusually pared down and solvent-exposed, a key element in molecular recognition by PRO is a lobe N-terminal to the catalytic domain. Docking models and the activities of PRO and PRO mutants in a deubiquitylating assay suggest that this N-terminal lobe is also likely involved in PRO's DUB function. Our data thus establish that DUBs can evolve to specifically hydrolyze both iso- and endopeptide bonds with different sequences. This is achieved by the use of multiple specificity determinants, as recognition of substrate patches distant from the cleavage sites allows a relaxed specificity of PRO at the sites themselves. Our results thus shed light on how such a compact protein achieves a diversity of key functions in viral genome replication and host-pathogen interaction.",2013 Aug 15,"['Lombardi, Charlotte', 'Ayach, Maya', 'Beaurepaire, Lionel', 'Chenon, Mélanie', 'Andreani, Jessica', 'Guerois, Raphaël', 'Jupin, Isabelle', 'Bressanelli, Stéphane']",PLoS Pathog,,,True
24ea6063ca2c39579eef84d27b3170e6d33a7e27,PMC,A Compact Viral Processing Proteinase/Ubiquitin Hydrolase from the OTU Family,http://dx.doi.org/10.1371/journal.ppat.1003560,PMC3744425,23966860,CC BY,"Turnip yellow mosaic virus (TYMV) - a member of the alphavirus-like supergroup of viruses - serves as a model system for positive-stranded RNA virus membrane-bound replication. TYMV encodes a precursor replication polyprotein that is processed by the endoproteolytic activity of its internal cysteine proteinase domain (PRO). We recently reported that PRO is actually a multifunctional enzyme with a specific ubiquitin hydrolase (DUB) activity that contributes to viral infectivity. Here, we report the crystal structure of the 150-residue PRO. Strikingly, PRO displays no homology to other processing proteinases from positive-stranded RNA viruses, including that of alphaviruses. Instead, the closest structural homologs of PRO are DUBs from the Ovarian tumor (OTU) family. In the crystal, one molecule's C-terminus inserts into the catalytic cleft of the next, providing a view of the N-terminal product complex in replication polyprotein processing. This allows us to locate the specificity determinants of PRO for its proteinase substrates. In addition to the catalytic cleft, at the exit of which the active site is unusually pared down and solvent-exposed, a key element in molecular recognition by PRO is a lobe N-terminal to the catalytic domain. Docking models and the activities of PRO and PRO mutants in a deubiquitylating assay suggest that this N-terminal lobe is also likely involved in PRO's DUB function. Our data thus establish that DUBs can evolve to specifically hydrolyze both iso- and endopeptide bonds with different sequences. This is achieved by the use of multiple specificity determinants, as recognition of substrate patches distant from the cleavage sites allows a relaxed specificity of PRO at the sites themselves. Our results thus shed light on how such a compact protein achieves a diversity of key functions in viral genome replication and host-pathogen interaction.",2013 Aug 15,"['Lombardi, Charlotte', 'Ayach, Maya', 'Beaurepaire, Lionel', 'Chenon, Mélanie', 'Andreani, Jessica', 'Guerois, Raphaël', 'Jupin, Isabelle', 'Bressanelli, Stéphane']",PLoS Pathog,,,True
68422d2849ca1b297e561f73160f9a74a7077797,PMC,Coronaviruses Lacking Exoribonuclease Activity Are Susceptible to Lethal Mutagenesis: Evidence for Proofreading and Potential Therapeutics,http://dx.doi.org/10.1371/journal.ppat.1003565,PMC3744431,23966862,CC BY,"No therapeutics or vaccines currently exist for human coronaviruses (HCoVs). The Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV) epidemic in 2002–2003, and the recent emergence of Middle East Respiratory Syndrome coronavirus (MERS-CoV) in April 2012, emphasize the high probability of future zoonotic HCoV emergence causing severe and lethal human disease. Additionally, the resistance of SARS-CoV to ribavirin (RBV) demonstrates the need to define new targets for inhibition of CoV replication. CoVs express a 3′-to-5′ exoribonuclease in nonstructural protein 14 (nsp14-ExoN) that is required for high-fidelity replication and is conserved across the CoV family. All genetic and biochemical data support the hypothesis that nsp14-ExoN has an RNA proofreading function. Thus, we hypothesized that ExoN is responsible for CoV resistance to RNA mutagens. We demonstrate that while wild-type (ExoN+) CoVs were resistant to RBV and 5-fluorouracil (5-FU), CoVs lacking ExoN activity (ExoN−) were up to 300-fold more sensitive. While the primary antiviral activity of RBV against CoVs was not mutagenesis, ExoN− CoVs treated with 5-FU demonstrated both enhanced sensitivity during multi-cycle replication, as well as decreased specific infectivity, consistent with 5-FU functioning as a mutagen. Comparison of full-genome next-generation sequencing of 5-FU treated SARS-CoV populations revealed a 16-fold increase in the number of mutations within the ExoN− population as compared to ExoN+. Ninety percent of these mutations represented A:G and U:C transitions, consistent with 5-FU incorporation during RNA synthesis. Together our results constitute direct evidence that CoV ExoN activity provides a critical proofreading function during virus replication. Furthermore, these studies identify ExoN as the first viral protein distinct from the RdRp that determines the sensitivity of RNA viruses to mutagens. Finally, our results show the importance of ExoN as a target for inhibition, and suggest that small-molecule inhibitors of ExoN activity could be potential pan-CoV therapeutics in combination with RBV or RNA mutagens.",2013 Aug 15,"['Smith, Everett Clinton', 'Blanc, Hervé', 'Vignuzzi, Marco', 'Denison, Mark R.']",PLoS Pathog,,,True
7b0e91e998988ff07f863db25fa8cc0d82ce1183,PMC,A Two-Tube Multiplex Reverse Transcription PCR Assay for Simultaneous Detection of Sixteen Human Respiratory Virus Types/Subtypes,http://dx.doi.org/10.1155/2013/327620,PMC3747601,23984344,CC BY,"There is a need for the development of a rapid and sensitive diagnosis of respiratory viral pathogens. With an intended application in provincial Centers for Diseases Control and Prevention, in this study, we present a two-tube multiplex RT-PCR assay (two-tube assay) using automatic electrophoresis to simultaneously detect sixteen common respiratory viruses. The specificity and the sensitivity of the assay were tested. The assay could detect 20–200 copies per reaction when each viral type was assayed individually, 2000 copies with 9 premixed viral targets in the multiplexed assay in tube 1, and 200 copies with 8 premixed templates in tube 2. A total of 247 specimens were used to evaluate the two-tube assay, and the results were compared with those obtained from the Luminex xTAG RVP Fast assay. The discordant results were confirmed by sequencing or by the Seeplex RV15 ACE detection kit. There were no false positives, but six false negatives occurred with the two-tube assay. In conclusion, the two-tube assay is demonstrated to have great potential for routine surveillance of respiratory virus infection in China.",2013 Aug 5,"['Li, Jin', 'Qi, Shunxiang', 'Zhang, Chen', 'Hu, Xiumei', 'Shen, Hongwei', 'Yang, Mengjie', 'Wang, Ji', 'Wang, Miao', 'Xu, Wenbo', 'Ma, Xuejun']",Biomed Res Int,,,True
790506537d41f8336265c309548c3f95759c7370,PMC,Enhanced Nasal Mucosal Delivery and Immunogenicity of Anti-Caries DNA Vaccine through Incorporation of Anionic Liposomes in Chitosan/DNA Complexes,http://dx.doi.org/10.1371/journal.pone.0071953,PMC3748075,23977186,CC BY,"The design of optimized nanoparticles offers a promising strategy to enable DNA vaccines to cross various physiological barriers for eliciting a specific and protective mucosal immunity via intranasal administration. Here, we reported a new designed nanoparticle system through incorporating anionic liposomes (AL) into chitosan/DNA (CS/DNA) complexes. With enhanced cellular uptake, the constructed AL/CS/DNA nanoparticles can deliver the anti-caries DNA vaccine pGJA-P/VAX into nasal mucosa. TEM results showed the AL/CS/DNA had a spherical structure. High DNA loading ability and effective DNA protection against nuclease were proved by gel electrophoresis. The surface charge of the AL/CS/DNA depended strongly on pH environment, enabling the intracellular release of loaded DNA via a pH-mediated manner. In comparison to the traditional CS/DNA system, our new design rendered a higher transfection efficiency and longer residence time of the AL/CS/DNA at nasal mucosal surface. These outstanding features enable the AL/CS/DNA to induce a significantly (p<0.01) higher level of secretory IgA (SIgA) than the CS/DNA in animal study, and a longer-term mucosal immunity. On the other hand, the AL/CS/DNA exhibited minimal cytotoxicity. These results suggest that the developed nanoparticles offer a potential platform for DNA vaccine packaging and delivery for more efficient elicitation of mucosal immunity.",2013 Aug 20,"['Chen, Liulin', 'Zhu, Junming', 'Li, Yuhong', 'Lu, Jie', 'Gao, Li', 'Xu, Huibi', 'Fan, Mingwen', 'Yang, Xiangliang']",PLoS One,,,True
dcbb50e1f581ab72a3070c7639c8c1a23e031c27,PMC,Metagenomic Analysis of the Ferret Fecal Viral Flora,http://dx.doi.org/10.1371/journal.pone.0071595,PMC3748082,23977082,CC BY,"Ferrets are widely used as a small animal model for a number of viral infections, including influenza A virus and SARS coronavirus. To further analyze the microbiological status of ferrets, their fecal viral flora was studied using a metagenomics approach. Novel viruses from the families Picorna-, Papilloma-, and Anelloviridae as well as known viruses from the families Astro-, Corona-, Parvo-, and Hepeviridae were identified in different ferret cohorts. Ferret kobu- and hepatitis E virus were mainly present in human household ferrets, whereas coronaviruses were found both in household as well as farm ferrets. Our studies illuminate the viral diversity found in ferrets and provide tools to prescreen for newly identified viruses that potentially could influence disease outcome of experimental virus infections in ferrets.",2013 Aug 20,"['Smits, Saskia L.', 'Raj, V. Stalin', 'Oduber, Minoushka D.', 'Schapendonk, Claudia M. E.', 'Bodewes, Rogier', 'Provacia, Lisette', 'Stittelaar, Koert J.', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.']",PLoS One,,,True
5eb34e4b386106962c368bb7c32db8995190e5c6,PMC,Measuring Social Contacts in the Emergency Department,http://dx.doi.org/10.1371/journal.pone.0070854,PMC3749132,23990915,CC BY,"BACKGROUND: Infectious individuals in an emergency department (ED) bring substantial risks of cross infection. Data about the complex social and spatial structure of interpersonal contacts in the ED will aid construction of biologically plausible transmission risk models that can guide cross infection control. METHODS AND FINDINGS: We sought to determine the number and duration of contacts among patients and staff in a large, busy ED. This prospective study was conducted between 1 July 2009 and 30 June 2010. Two 12-hour shifts per week were randomly selected for study. The study was conducted in the ED of an urban hospital. There were 81 shifts in the planned random sample of 104 (78%) with usable contact data, during which there were 9183 patient encounters. Of these, 6062 (66%) were approached to participate, of which 4732 (78%) agreed. Over the course of the year, 88 staff members participated (84%). A radiofrequency identification (RFID) system was installed and the ED divided into 89 distinct zones structured so copresence of two individuals in any zone implied a very high probability of contact <1 meter apart in space. During study observation periods, patients and staff were given RFID tags to wear. Contact events were recorded. These were further broken down with respect to the nature of the contacts, i.e., patient with patient, patient with staff, and staff with staff. 293,171 contact events were recorded, with a median of 22 contact events and 9 contacts with distinct individuals per participant per shift. Staff-staff interactions were more numerous and longer than patient-patient or patient-staff interactions. CONCLUSIONS: We used RFID to quantify contacts between patients and staff in a busy ED. These results are useful for studies of the spread of infections. By understanding contact patterns most important in potential transmission, more effective prevention strategies may be implemented.",2013 Aug 21,"['Lowery-North, Douglas W.', 'Hertzberg, Vicki Stover', 'Elon, Lisa', 'Cotsonis, George', 'Hilton, Sarah A.', 'Vaughns, Christopher F.', 'Hill, Eric', 'Shrestha, Alok', 'Jo, Alexandria', 'Adams, Nathan']",PLoS One,,,True
a013535d6925d423b5d999a4b2e1ded678e190a6,PMC,Causes of Mortality for Indonesian Hajj Pilgrims: Comparison between Routine Death Certificate and Verbal Autopsy Findings,http://dx.doi.org/10.1371/journal.pone.0073243,PMC3749149,23991182,CC BY,"BACKGROUND: Indonesia provides the largest single source of pilgrims for the Hajj (10%). In the last two decades, mortality rates for Indonesian pilgrims ranged between 200–380 deaths per 100,000 pilgrims over the 10-week Hajj period. Reasons for high mortality are not well understood. In 2008, verbal autopsy was introduced to complement routine death certificates to explore cause of death diagnoses. This study presents the patterns and causes of death for Indonesian pilgrims, and compares routine death certificates to verbal autopsy findings. METHODS: Public health surveillance was conducted by Indonesian public health authorities accompanying pilgrims to Saudi Arabia, with daily reporting of hospitalizations and deaths. Surveillance data from 2008 were analyzed for timing, geographic location and site of death. Percentages for each cause of death category from death certificates were compared to that from verbal autopsy. RESULTS: In 2008, 206,831 Indonesian undertook the Hajj. There were 446 deaths, equivalent to 1,968 deaths per 100,000 pilgrim years. Most pilgrims died in Mecca (68%) and Medinah (24%). There was no statistically discernible difference in the total mortality risk for the two pilgrimage routes (Mecca or Medinah first), but the number of deaths peaked earlier for those traveling to Mecca first (p=0.002). Most deaths were due to cardiovascular (66%) and respiratory (28%) diseases. A greater proportion of deaths were attributed to cardiovascular disease by death certificate compared to the verbal autopsy method (p<0.001). Significantly more deaths had ill-defined cause based on verbal autopsy method (p<0.001). CONCLUSIONS: Despite pre-departure health screening and other medical services, Indonesian pilgrim mortality rates were very high. Correct classification of cause of death is critical for the development of risk mitigation strategies. Since verbal autopsy classified causes of death differently to death certificates, further studies are needed to assess the method’s utility in this setting.",2013 Aug 21,"['Pane, Masdalina', 'Imari, Sholah', 'Alwi, Qomariah', 'Nyoman Kandun, I', 'Cook, Alex R.', 'Samaan, Gina']",PLoS One,,,True
300778fc251628966c3c027308a7d3fe5a02f84c,PMC,MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment,http://dx.doi.org/10.1099/vir.0.052910-0,PMC3749523,23620378,CC BY,"Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. The 2003 outbreak of severe acute respiratory syndrome (SARS) highlighted the potentially lethal consequences of CoV-induced disease in humans. In 2012, a novel CoV (Middle East Respiratory Syndrome coronavirus; MERS-CoV) emerged, causing 49 human cases thus far, of which 23 had a fatal outcome. In this study, we characterized MERS-CoV replication and cytotoxicity in human and monkey cell lines. Electron microscopy of infected Vero cells revealed extensive membrane rearrangements, including the formation of double-membrane vesicles and convoluted membranes, which have been implicated previously in the RNA synthesis of SARS-CoV and other CoVs. Following infection, we observed rapidly increasing viral RNA synthesis and release of high titres of infectious progeny, followed by a pronounced cytopathology. These characteristics were used to develop an assay for antiviral compound screening in 96-well format, which was used to identify cyclosporin A as an inhibitor of MERS-CoV replication in cell culture. Furthermore, MERS-CoV was found to be 50–100 times more sensitive to alpha interferon (IFN-α) treatment than SARS-CoV, an observation that may have important implications for the treatment of MERS-CoV-infected patients. MERS-CoV infection did not prevent the IFN-induced nuclear translocation of phosphorylated STAT1, in contrast to infection with SARS-CoV where this block inhibits the expression of antiviral genes. These findings highlight relevant differences between these distantly related zoonotic CoVs in terms of their interaction with and evasion of the cellular innate immune response.",2013 Aug,"['de Wilde, Adriaan H.', 'Raj, V. Stalin', 'Oudshoorn, Diede', 'Bestebroer, Theo M.', 'van Nieuwkoop, Stefan', 'Limpens, Ronald W. A. L.', 'Posthuma, Clara C.', 'van der Meer, Yvonne', 'Bárcena, Montserrat', 'Haagmans, Bart L.', 'Snijder, Eric J.', 'van den Hoogen, Bernadette G.']",J Gen Virol,,,True
4afc459e347836f0f92a75ab0c6cbe2e02e6f3a4,PMC,"Proposals for the classification of human rhinovirus species A, B and C into genotypically assigned types",http://dx.doi.org/10.1099/vir.0.053686-0,PMC3749525,23677786,CC BY,"Human rhinoviruses (HRVs) frequently cause mild upper respiratory tract infections and more severe disease manifestations such as bronchiolitis and asthma exacerbations. HRV is classified into three species within the genus Enterovirus of the family Picornaviridae. HRV species A and B contain 75 and 25 serotypes identified by cross-neutralization assays, although the use of such assays for routine HRV typing is hampered by the large number of serotypes, replacement of virus isolation by molecular methods in HRV diagnosis and the poor or absent replication of HRV species C in cell culture. To address these problems, we propose an alternative, genotypic classification of HRV-based genetic relatedness analogous to that used for enteroviruses. Nucleotide distances between 384 complete VP1 sequences of currently assigned HRV (sero)types identified divergence thresholds of 13, 12 and 13 % for species A, B and C, respectively, that divided inter- and intra-type comparisons. These were paralleled by 10, 9.5 and 10 % thresholds in the larger dataset of >3800 VP4 region sequences. Assignments based on VP1 sequences led to minor revisions of existing type designations (such as the reclassification of serotype pairs, e.g. A8/A95 and A29/A44, as single serotypes) and the designation of new HRV types A101–106, B101–103 and C34–C51. A protocol for assignment and numbering of new HRV types using VP1 sequences and the restriction of VP4 sequence comparisons to type identification and provisional type assignments is proposed. Genotypic assignment and identification of HRV types will be of considerable value in the future investigation of type-associated differences in disease outcomes, transmission and epidemiology.",2013 Aug,"['McIntyre, Chloe L.', 'Knowles, Nick J.', 'Simmonds, Peter']",J Gen Virol,,,True
881abbe78ba9d6d7a690c15464342d1730f327cd,PMC,Identification of MicroRNA-Like RNAs in Mycelial and Yeast Phases of the Thermal Dimorphic Fungus Penicillium marneffei,http://dx.doi.org/10.1371/journal.pntd.0002398,PMC3749987,23991243,CC BY,"BACKGROUND: Penicillium marneffei is the most important thermal dimorphic fungus causing systemic mycosis in China and Southeast Asia. While miRNAs are increasingly recognized for their roles in post-transcriptional regulation of gene expression in animals and plants, miRNAs in fungi were less well studied and their potential roles in fungal dimorphism were largely unknown. Based on P. marneffei genome sequence, we hypothesize that miRNA-like RNAs (milRNAs) may be expressed in the dimorphic fungus. METHODOLOGY/PRINCIPAL FINDINGS: We attempted to identify milRNAs in P. marneffei in both mycelial and yeast phase using high-throughput sequencing technology. Small RNAs were more abundantly expressed in mycelial than yeast phase. Sequence analysis revealed 24 potential milRNA candidates, including 17 candidates in mycelial and seven in yeast phase. Two genes, dcl-1 and dcl-2, encoding putative Dicer-like proteins and the gene, qde-2, encoding Argonaute-like protein, were identified in P. marneffei. Phylogenetic analysis showed that dcl-2 of P. marneffei was more closely related to the homologues in other thermal dimorphic pathogenic fungi than to Penicillium chrysogenum and Aspergillus spp., suggesting the co-evolution of dcl-2 among the thermal dimorphic fungi. Moreover, dcl-2 demonstrated higher mRNA expression levels in mycelial than yeast phase by 7 folds (P<0.001). Northern blot analysis confirmed the expression of two milRNAs, PM-milR-M1 and PM-milR-M2, only in mycelial phase. Using dcl-1(KO), dcl-2(KO), dcl(DKO) and qde-2(KO) deletion mutants, we showed that the biogenesis of both milRNAs were dependent on dcl-2 but not dcl-1 or qde-2. The mRNA expression levels of three predicted targets of PM-milR-M1 were upregulated in knockdown strain PM-milR-M1 (KD), supporting regulatory function of milRNAs. CONCLUSIONS/SIGNIFICANCE: Our findings provided the first evidence for differential expression of milRNAs in different growth phases of thermal dimorphic fungi and shed light on the evolution of fungal proteins involved in milRNA biogenesis and possible role of post-transcriptional control in governing thermal dimorphism.",2013 Aug 22,"['Lau, Susanna K. P.', 'Chow, Wang-Ngai', 'Wong, Annette Y. P.', 'Yeung, Julian M. Y.', 'Bao, Jessie', 'Zhang, Na', 'Lok, Si', 'Woo, Patrick C. Y.', 'Yuen, Kwok-Yung']",PLoS Negl Trop Dis,,,True
682a9c91d32a70c08413f3c3f0daba54239c0af0,PMC,Historical Epidemiology of the Second Cholera Pandemic: Relevance to Present Day Disease Dynamics,http://dx.doi.org/10.1371/journal.pone.0072498,PMC3749991,23991117,CC BY,"Despite nearly two centuries of study, the fundamental transmission dynamic properties of cholera remain incompletely characterized. We used historical time-series data on the spread of cholera in twelve European and North American cities during the second cholera pandemic, as reported in Amariah Brigham’s 1832 A Treatise on Epidemic Cholera, to parameterize simple mathematical models of cholera transmission. Richards growth models were used to derive estimates of the basic reproductive number (R(0)) (median: 16.0, range: 1.9 to 550.9) and the proportion of unrecognized cases (mean: 96.3%, SD: 0.04%). Heterogeneity in model-generated R(0) estimates was consistent with variability in cholera dynamics described by contemporary investigators and may represent differences in the nature of cholera spread. While subject to limitations associated with measurement and the absence of microbiological diagnosis, historical epidemic data are a potentially rich source for understanding pathogen dynamics in the absence of control measures, particularly when used in conjunction with simple and readily interpretable mathematical models.",2013 Aug 22,"['Chan, Christina H.', 'Tuite, Ashleigh R.', 'Fisman, David N.']",PLoS One,,,True
89f70b62cc7e6aa71fbebcc3194b4ea5ad756c99,PMC,Viral Etiology and Clinical Profiles of Children with Severe Acute Respiratory Infections in China,http://dx.doi.org/10.1371/journal.pone.0072606,PMC3750056,23991128,CC BY,"BACKGROUND: No comprehensive analysis is available on the viral etiology and clinical characterization among children with severe acute respiratory infection (SARI) in China during 2009 H1N1 pandemic and post-pandemic period. METHODS: Cohort of 370 hospitalized children (1 to 72 months) with SARI from May 2008 to March 2010 was enrolled in this study. Nasopharyngeal aspirate (NPA) specimens were tested by a commercial assay for 18 respiratory viral targets. The viral distribution and its association with clinical character were statistically analyzed. RESULTS: Viral pathogen was detected in 350 (94.29%) of children with SARI. Overall, the most popular viruses were: enterovirus/rhinovirus (EV/RV) (54.05%), respiratory syncytial virus (RSV) (51.08%), human bocavirus (BoCA) (33.78%), human parainfluenzaviruse type 3 (PIV3) (15.41%), and adenovirus (ADV) (12.97%). Pandemic H1N1 was the dominant influenza virus (IFV) but was only detected in 20 (5.41%) of children. Moreover, detection rate of RSV and human metapneumovirus (hMPV) among suburb participants were significantly higher than that of urban area (P<0.05). Incidence of VSARI among suburb participants was also significant higher, especially among those of 24 to 59 months group (P<0.05). CONCLUSION: Piconaviruses (EV/RV) and paramyxoviruses are the most popular viral pathogens among children with SARI in this study. RSV and hMPV significantly increase the risk of SARI, especially in children younger than 24 months. Higher incidence of VSARI and more susceptibilities to RSV and hMPV infections were found in suburban patients.",2013 Aug 22,"['Zhang, Chen', 'Zhu, Na', 'Xie, Zhengde', 'Lu, Roujian', 'He, Bin', 'Liu, Chunyan', 'Ma, Xuejun', 'Tan, Wenjie']",PLoS One,,,True
ec2b2544b77c203db7fb59fbcb3f2c12733685e1,PMC,The protective effect of recombinant Lactococcus lactis oral vaccine on a Clostridium difficile-infected animal model,http://dx.doi.org/10.1186/1471-230X-13-117,PMC3750240,23865596,CC BY,"BACKGROUND: Oral immunization with vaccines may be an effective strategy for prevention of Clostridium difficile infection (CDI). However, application of previously developed vaccines for preventing CDI has been limited due to various reasons. Here, we developed a recombinant Lactococcus lactis oral vaccine and evaluated its effect on a C. difficile-infected animal model established in golden hamsters in attempt to provide an alternative strategy for CDI prevention. METHODS: Recombinant L. lactis vaccine was developed using the pTRKH2 plasmid, a high-copy-number Escherichia coli-L. shuttle vector: 1) L. lactis expressing secreted proteins was constructed with recombinant pTRKH2 (secreted-protein plasmid) carrying the Usp45 signal peptide (SPUsp45), nontoxic adjuvanted tetanus toxin fragment C (TETC), and 14 of the 38 C-terminal repeats (14CDTA) of nontoxic C. difficile toxin A (TcdA); and 2) L. lactis expressing secreted and membrane proteins was constructed with recombinant pTRKH2 (membrane-anchored plasmid) carrying SPUsp45, TETC, 14CDTA, and the cell wall-anchored sequence of protein M6 (cwaM6). Then, 32 male Syrian golden hamsters were randomly divided into 4 groups (n = 8 each) for gavage of normal saline (blank control) and L. lactis carrying the empty shuttle vector, secreted-protein plasmid, and membrane-anchored plasmid, respectively. After 1-week gavage of clindamycin, the animals were administered with C. difficile spore suspension. General symptoms and intestinal pathological changes of the animals were examined by naked eye and microscopy, respectively. Protein levels of anti-TcdA IgG/IgA antibodies in intestinal tissue and fluid were analyzed by enzyme-linked immunosorbent assay (ELISA). A cell culture cytotoxicity neutralization assay was done by TcdA treatment with or without anti-TcdA serum pre-incubation or treatment. Apoptosis of intestinal epithelial cells was examined by flow cytometry (FL) assay. Expression of mucosal inflammatory cytokines in the animals was detected by polymer chain reaction (PCR) assay. RESULTS: After the C. difficile challenge, the animals of control group had severe diarrhea symptoms on day 1 and all died on day 4, indicating that the CDI animal model was established in hamster. Of the 3 immunization groups, secreted-protein and membrane-anchored plasmid groups had significantly lower mortalities, body weight decreases, and pathological scores, with higher survival rate/time than the empty plasmid group (P < 0.05). The tilter of IgG antibody directed against TcdA was significantly higher in serum and intestinal fluid of secreted-protein and membrane-anchored plasmid groups than in the empty plasmid group (P < 0.05) while the corresponding titer of IgA antibody directed against TcdA had no substantial differences (P > 0.05). The anti-TcdA serum of membrane-anchored plasmid group neutralized the cytotoxicity of 200 ng/ml TcdA with the best protective effect achieved by anti-TcdA serum pre-incubation. The incidences of TcdA-induced death and apoptosis of intestinal epithelial cells were significantly reduced by cell pre-incubation or treatment with anti-TcdA serum of membrane-anchored plasmid group (P < 0.05). MCP-1, ICAM-1, IL-6, and Gro-1 mRNA expression levels were the lowest in cecum tissue of the membrane-anchored groups compared to the other groups. CONCLUSION: Recombinant L. lactis live vaccine is effective for preventing CDI in the hamster model, thus providing an alternative for immunization of C. difficile-associated diseases.",2013 Jul 17,"['Yang, Xiao-qiang', 'Zhao, Ya-gang', 'Chen, Xue-qing', 'Jiang, Bo', 'Sun, Da-yong']",BMC Gastroenterol,,,True
5e80e58924fd2feae8218fc7c2c066e75cec0149,PMC,Level of colorectal cancer awareness: a cross sectional exploratory study among multi-ethnic rural population in Malaysia,http://dx.doi.org/10.1186/1471-2407-13-376,PMC3750380,23924238,CC BY,"BACKGROUND: This paper presents the level of colorectal cancer awareness among multi-ethnic rural population in Malaysia. METHODS: A rural-based cross sectional survey was carried out in Perak state in Peninsular Malaysia in March 2011. The survey recruited a population-representative sample using multistage sampling. Altogether 2379 participants were included in this study. Validated bowel/colorectal cancer awareness measure questionnaire was used to assess the level of colorectal cancer awareness among study population. Analysis of variance (ANOVA) was done to identify socio-demographic variance of knowledge score on warning signs and risk factors of colorectal cancer. RESULTS: Among respondents, 38% and 32% had zero knowledge score for warning signs and risk factors respectively. Mean knowledge score for warning signs and risk factors were 2.89 (SD 2.96) and 3.49 (SD 3.17) respectively. There was a significant positive correlation between the knowledge score of warning signs and level of confidence in detecting a warning sign. Socio-demographic characteristics and having cancer in family and friends play important role in level of awareness. CONCLUSIONS: Level of awareness on colorectal cancer warning signs and risk factors in the rural population of Malaysia is very low. Therefore, it warrants an extensive health education campaign on colorectal cancer awareness as it is one of the commonest cancer in Malaysia. Health education campaign is urgently needed because respondents would seek medical attention sooner if they are aware of this problem.",2013 Aug 7,"['Su, Tin Tin', 'Goh, Jun Yan', 'Tan, Jackson', 'Muhaimah, Abdul Rahim', 'Pigeneswaren, Yoganathan', 'Khairun, Nasirin Sallamun', 'Normazidah, Abdul Wahab', 'Tharisini, Devi Kunasekaran', 'Majid, Hazreen Abd']",BMC Cancer,,,True
ebda8d8ac0eb08bf9bd1c3bc80610f72572d1a73,PMC,Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice,http://dx.doi.org/10.1186/1752-0509-7-69,PMC3750405,23895213,CC BY,"BACKGROUND: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators – and the relative contributions of each toward viral pathogenicity – is not well-understood. RESULTS: By analyzing a collection of lung samples from mice infected by A/Vietnam/1203/2004 (H5N1; VN1203), we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A/California/04/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer. CONCLUSIONS: We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of ‘omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses.",2013 Jul 29,"['Tchitchek, Nicolas', 'Eisfeld, Amie J', 'Tisoncik-Go, Jennifer', 'Josset, Laurence', 'Gralinski, Lisa E', 'Bécavin, Christophe', 'Tilton, Susan C', 'Webb-Robertson, Bobbie-Jo', 'Ferris, Martin T', 'Totura, Allison L', 'Li, Chengjun', 'Neumann, Gabriele', 'Metz, Thomas O', 'Smith, Richard D', 'Waters, Katrina M', 'Baric, Ralph', 'Kawaoka, Yoshihiro', 'Katze, Michael G']",BMC Syst Biol,,,True
9ef9504a4ff66e04887a8ea7d2050b8e11e3089e,PMC,Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice,http://dx.doi.org/10.1186/1752-0509-7-69,PMC3750405,23895213,CC BY,"BACKGROUND: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators – and the relative contributions of each toward viral pathogenicity – is not well-understood. RESULTS: By analyzing a collection of lung samples from mice infected by A/Vietnam/1203/2004 (H5N1; VN1203), we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A/California/04/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer. CONCLUSIONS: We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of ‘omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses.",2013 Jul 29,"['Tchitchek, Nicolas', 'Eisfeld, Amie J', 'Tisoncik-Go, Jennifer', 'Josset, Laurence', 'Gralinski, Lisa E', 'Bécavin, Christophe', 'Tilton, Susan C', 'Webb-Robertson, Bobbie-Jo', 'Ferris, Martin T', 'Totura, Allison L', 'Li, Chengjun', 'Neumann, Gabriele', 'Metz, Thomas O', 'Smith, Richard D', 'Waters, Katrina M', 'Baric, Ralph', 'Kawaoka, Yoshihiro', 'Katze, Michael G']",BMC Syst Biol,,,False
4e7ebe0cfdc55c3e8cac563b6d787445d7121a01,PMC,Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice,http://dx.doi.org/10.1186/1752-0509-7-69,PMC3750405,23895213,CC BY,"BACKGROUND: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators – and the relative contributions of each toward viral pathogenicity – is not well-understood. RESULTS: By analyzing a collection of lung samples from mice infected by A/Vietnam/1203/2004 (H5N1; VN1203), we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A/California/04/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer. CONCLUSIONS: We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of ‘omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses.",2013 Jul 29,"['Tchitchek, Nicolas', 'Eisfeld, Amie J', 'Tisoncik-Go, Jennifer', 'Josset, Laurence', 'Gralinski, Lisa E', 'Bécavin, Christophe', 'Tilton, Susan C', 'Webb-Robertson, Bobbie-Jo', 'Ferris, Martin T', 'Totura, Allison L', 'Li, Chengjun', 'Neumann, Gabriele', 'Metz, Thomas O', 'Smith, Richard D', 'Waters, Katrina M', 'Baric, Ralph', 'Kawaoka, Yoshihiro', 'Katze, Michael G']",BMC Syst Biol,,,False
8670e7c9c70220663ce166e38e0adba8c6d7de18,PMC,Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice,http://dx.doi.org/10.1186/1752-0509-7-69,PMC3750405,23895213,CC BY,"BACKGROUND: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators – and the relative contributions of each toward viral pathogenicity – is not well-understood. RESULTS: By analyzing a collection of lung samples from mice infected by A/Vietnam/1203/2004 (H5N1; VN1203), we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A/California/04/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer. CONCLUSIONS: We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of ‘omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses.",2013 Jul 29,"['Tchitchek, Nicolas', 'Eisfeld, Amie J', 'Tisoncik-Go, Jennifer', 'Josset, Laurence', 'Gralinski, Lisa E', 'Bécavin, Christophe', 'Tilton, Susan C', 'Webb-Robertson, Bobbie-Jo', 'Ferris, Martin T', 'Totura, Allison L', 'Li, Chengjun', 'Neumann, Gabriele', 'Metz, Thomas O', 'Smith, Richard D', 'Waters, Katrina M', 'Baric, Ralph', 'Kawaoka, Yoshihiro', 'Katze, Michael G']",BMC Syst Biol,,,False
235a2dcaae4126e0c1afeb28607fc683d4a6bfbb,PMC,Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice,http://dx.doi.org/10.1186/1752-0509-7-69,PMC3750405,23895213,CC BY,"BACKGROUND: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators – and the relative contributions of each toward viral pathogenicity – is not well-understood. RESULTS: By analyzing a collection of lung samples from mice infected by A/Vietnam/1203/2004 (H5N1; VN1203), we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A/California/04/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer. CONCLUSIONS: We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of ‘omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses.",2013 Jul 29,"['Tchitchek, Nicolas', 'Eisfeld, Amie J', 'Tisoncik-Go, Jennifer', 'Josset, Laurence', 'Gralinski, Lisa E', 'Bécavin, Christophe', 'Tilton, Susan C', 'Webb-Robertson, Bobbie-Jo', 'Ferris, Martin T', 'Totura, Allison L', 'Li, Chengjun', 'Neumann, Gabriele', 'Metz, Thomas O', 'Smith, Richard D', 'Waters, Katrina M', 'Baric, Ralph', 'Kawaoka, Yoshihiro', 'Katze, Michael G']",BMC Syst Biol,,,False
a666fb5ccc487de7063bca9a179137052c0eeff1,PMC,Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice,http://dx.doi.org/10.1186/1752-0509-7-69,PMC3750405,23895213,CC BY,"BACKGROUND: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators – and the relative contributions of each toward viral pathogenicity – is not well-understood. RESULTS: By analyzing a collection of lung samples from mice infected by A/Vietnam/1203/2004 (H5N1; VN1203), we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A/California/04/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer. CONCLUSIONS: We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of ‘omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses.",2013 Jul 29,"['Tchitchek, Nicolas', 'Eisfeld, Amie J', 'Tisoncik-Go, Jennifer', 'Josset, Laurence', 'Gralinski, Lisa E', 'Bécavin, Christophe', 'Tilton, Susan C', 'Webb-Robertson, Bobbie-Jo', 'Ferris, Martin T', 'Totura, Allison L', 'Li, Chengjun', 'Neumann, Gabriele', 'Metz, Thomas O', 'Smith, Richard D', 'Waters, Katrina M', 'Baric, Ralph', 'Kawaoka, Yoshihiro', 'Katze, Michael G']",BMC Syst Biol,,,False
aab412e1a2fee75cf3e3fbc911d985ac004f866e,PMC,Probiotic Lactobacillus rhamnosus GG mono-association suppresses human rotavirus-induced autophagy in the gnotobiotic piglet intestine,http://dx.doi.org/10.1186/1757-4749-5-22,PMC3750464,23924832,CC BY,"BACKGROUND: Human rotavirus (HRV) is the most important cause of severe diarrhea in infants and young children. Probiotic Lactobacillus rhamnosus GG (LGG) reduces rotavirus infection and diarrhea. However, the molecular mechanisms of LGG-mediated protection from rotavirus infection are poorly understood. Autophagy plays an essential role in responses to microbial pathogens. However, the role of autophagy in HRV infection and LGG treatment is unknown. We hypothesize that rotavirus gastroenteritis activates autophagy and that LGG suppresses virus-induced autophagy and prevents intestinal damage in infected piglets. METHODS: We used LGG feeding to combat viral gastroenteritis in the gnotobiotic pig model of virulent HRV infection. RESULTS: We found that LGG feeding did not increase autophagy, whereas virus infection induced autophagy in the piglet intestine. Virus infection increased the protein levels of the autophagy markers ATG16L1 and Beclin-1 and the autophagy regulator mTOR. LGG treatment during viral gastroenteritis reduced autophagy marker expression to normal levels, induced apoptosis and partially prevented virus-induced tissue damage. CONCLUSION: Our study provides new insights into virus-induced autophagy and LGG suppression of uncontrolled autophagy and intestinal injury. A better understanding of the antiviral activity of LGG will lead to novel therapeutic strategies for infant infectious diseases.",2013 Aug 7,"['Wu, Shaoping', 'Yuan, Lijuan', 'Zhang, Yongguo', 'Liu, Fangning', 'Li, Guohua', 'Wen, Ke', 'Kocher, Jacob', 'Yang, Xingdong', 'Sun, Jun']",Gut Pathog,,,True
6d20ab75d7394461e9acd16899bd55902177d8fe,PMC,Initiation of human astrovirus type 1 infection was blocked by inhibitors of phosphoinositide 3-kinase,http://dx.doi.org/10.1186/1743-422X-10-153,PMC3750554,23680019,CC BY,"BACKGROUND: Upon initial contact with a virus, host cells activate a series of cellular signaling cascades that facilitate viral entry and viral propagation within the cell. Little is known about how the human astrovirus (HAstV) exploits signaling cascades to establish an infection in host cells. Recent studies showed that activation of extracellular signal-regulated kinase 1/2 (ERK1/2) is important for HAstV infection, though the involvement of other signaling cascades remains unclear. METHODS: A panel of kinase blockers was used to search for cellular signaling pathways important for HAstV1 infection. To determine their impact on the infectious process, we examined viral gene expression, RNA replication, and viral RNA and capsid protein release from host cells. RESULTS: Inhibitors of phosphoinositide 3-kinase (PI3K) activation interfered with the infection, independent of their effect on ERK 1/2 activation. Activation of the PI3K signaling cascade occurred at an early phase of the infection, judging from the timeframe of Akt phosphorylation. PI3K inhibition at early times, but not at later times, blocked viral gene expression. However, inhibiting the downstream targets of PI3K activation, Akt and Rac1, did not block infection. Inhibition of protein kinase A (PKA) activation was found to block a later phase of HAstV1 production. CONCLUSIONS: Our results reveal a previously unknown, essential role of PI3K in the life cycle of HAstV1. PI3K participates in the early stage of infection, possibly during the viral entry process. Our results also reveal the role of PKA in viral production.",2013 May 16,"['Tange, Shoichiro', 'Zhou, Yan', 'Nagakui-Noguchi, Yuko', 'Imai, Takeshi', 'Nakanishi, Akira']",Virol J,,,True
cf66e218ffa8ed3d638c5ddff568753609aac808,PMC,Changing trends and serotype distribution of Shigella species in Beijing from 1994 to 2010,http://dx.doi.org/10.1186/1757-4749-5-21,PMC3750644,23919811,CC BY,"Shigella species are a common cause of acute diarrheal disease in China. In this study, we characterized the changing trends and serotype distribution of Shigella species in Beijing from 1994 to 2010. A total of 5999 Shigella strains were isolated and serotyped from the 302nd Hospital in Beijing. The annual number of Shigella isolates reached a peak (n = 1192; 19.84%) in 1996 and then decreased annually, reaching the lowest point (n = 24; 0.41%) in 2010. S. flexneri 2a and S. sonnei were the most frequently isolated Shigella, with their respective isolates making up 53.3% and 27.6% of the total. Isolates of S. flexneri 4c, 4a, and x made up 3% respectively of the total isolates. Significant decreases in percentage of S. flexneri over time were observed. S. sonnei surpassed S. flexneri 2a as the predominant serotype in 2000. Most isolates were recovered from July to September; 13.6% of the isolates were recovered from children aged 0 to 5 years, and 16% were recovered from those aged 21 to 25 years. S. flexneri 2a and 5 were recovered mostly from males (33.41%, p < 0.001; and 0.46%, p < 0.001%; respectively), whereas S. flexneri 2b and 6, and S. sonnei were most often isolated from females. Continuous monitoring of Shigella showed that all 4 species and 27 serotypes were present in Beijing, China, during the study period. The emergence of S. sonnei and the overall decreasing isolation rate of Shigella in Beijing can potentially aid in the development of vaccine and control strategies for shigellosis in the city.",2013 Aug 7,"['Mao, Yuanli', 'Cui, Enbo', 'Bao, Chunmei', 'Liu, Zhenhong', 'Chen, Suming', 'Zhang, Juling', 'Wang, Huan', 'Zhang, Chenglong', 'Zou, Jing', 'Klena, John D', 'Zhu, Baoli', 'Qu, Fen', 'Wang, Zhiyun']",Gut Pathog,,,True
7c0bfcf7cdb720113a16c54e8203111137ebbd41,PMC,Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry,http://dx.doi.org/10.1186/1471-2180-13-187,PMC3750913,23924316,CC BY,"BACKGROUND: We previously identified two hydrolyzable tannins, chebulagic acid (CHLA) and punicalagin (PUG) that blocked herpes simplex virus type 1 (HSV-1) entry and spread. These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs). Based on this property, we evaluated their antiviral efficacy against several different viruses known to employ GAGs for host cell entry. RESULTS: Extensive analysis of the tannins’ mechanism of action was performed on a panel of viruses during the attachment and entry steps of infection. Virus-specific binding assays and the analysis of viral spread during treatment with these compounds were also conducted. CHLA and PUG were effective in abrogating infection by human cytomegalovirus (HCMV), hepatitis C virus (HCV), dengue virus (DENV), measles virus (MV), and respiratory syncytial virus (RSV), at μM concentrations and in dose-dependent manners without significant cytotoxicity. Moreover, the natural compounds inhibited viral attachment, penetration, and spread, to different degrees for each virus. Specifically, the tannins blocked all these steps of infection for HCMV, HCV, and MV, but had little effect on the post-fusion spread of DENV and RSV, which could suggest intriguing differences in the roles of GAG-interactions for these viruses. CONCLUSIONS: CHLA and PUG may be of value as broad-spectrum antivirals for limiting emerging/recurring viruses known to engage host cell GAGs for entry. Further studies testing the efficacy of these tannins in vivo against certain viruses are justified.",2013 Aug 7,"['Lin, Liang-Tzung', 'Chen, Ting-Ying', 'Lin, Song-Chow', 'Chung, Chueh-Yao', 'Lin, Ta-Chen', 'Wang, Guey-Horng', 'Anderson, Robert', 'Lin, Chun-Ching', 'Richardson, Christopher D']",BMC Microbiol,,,True
40886c8a1c173dab7ef1685c544a7554f63bd6ff,PMC,Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease,http://dx.doi.org/10.1186/1741-7015-11-181,PMC3750926,23945277,CC BY,"Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.",2013 Aug 14,"['Wedzicha, Jadwiga A', 'Brill, Simon E', 'Allinson, James P', 'Donaldson, Gavin C']",BMC Med,,,True
a09a978336b5c98928dbfb37b12da84d327bfe2d,PMC,Viral protein R of human immunodeficiency virus type-1 induces retrotransposition of long interspersed element-1,http://dx.doi.org/10.1186/1742-4690-10-83,PMC3751050,23915234,CC BY,"BACKGROUND: Viral protein R (Vpr), a protein of human immunodeficiency virus type-1 (HIV-1) with various biological functions, was shown to be present in the blood of HIV-1-positive patients. However, it remained unclear whether circulating Vpr in patients’ blood is biologically active. Here, we examined the activity of blood Vpr using an assay system by which retrotransposition of long interspersed element-1 (L1-RTP) was detected. We also investigated the in vivo effects of recombinant Vpr (rVpr) by administrating it to transgenic mice harboring human L1 as a transgene (hL1-Tg mice). Based on our data, we discuss the involvement of blood Vpr in the clinical symptoms of acquired immunodeficiency syndrome (AIDS). RESULTS: We first discovered that rVpr was active in induction of L1-RTP. Biochemical analyses revealed that rVpr-induced L1-RTP depended on the aryl hydrocarbon receptor, mitogen-activated protein kinases, and CCAAT/enhancer-binding protein β. By using a sensitive L1-RTP assay system, we showed that 6 of the 15 blood samples from HIV-1 patients examined were positive for induction of L1-RTP. Of note, the L1-RTP-inducing activity was blocked by a monoclonal antibody specific for Vpr. Moreover, L1-RTP was reproducibly induced in various organs, including the kidney, when rVpr was administered to hL1-Tg mice. CONCLUSIONS: Blood Vpr is biologically active, suggesting that its monitoring is worthwhile for clarification of the roles of Vpr in the pathogenesis of AIDS. This is the first report to demonstrate a soluble factor in patients’ blood active for L1-RTP activity, and implies the involvement of L1-RTP in the development of human diseases.",2013 Aug 5,"['Iijima, Kenta', 'Okudaira, Noriyuki', 'Tamura, Masato', 'Doi, Akihiro', 'Saito, Yoshikazu', 'Shimura, Mari', 'Goto, Motohito', 'Matsunaga, Akihiro', 'Kawamura, Yuki I', 'Otsubo, Takeshi', 'Dohi, Taeko', 'Hoshino, Shigeki', 'Kano, Shigeyuki', 'Hagiwara, Shotaro', 'Tanuma, Junko', 'Gatanaga, Hiroyuki', 'Baba, Masanori', 'Iguchi, Taku', 'Yanagita, Motoko', 'Oka, Shinichi', 'Okamura, Tadashi', 'Ishizaka, Yukihito']",Retrovirology,,,True
35105bb6ba037441c3366e7ea8d59dbcb9245c1b,PMC,Frequency of D222G haemagglutinin mutant of pandemic (H1N1) pdm09 influenza virus in Tunisia between 2009 and 2011,http://dx.doi.org/10.1186/1746-1596-8-124,PMC3751102,23902660,CC BY,"BACKGROUND: The novel pandemic A (H1N1) pdm09 virus was first identified in Mexico in April 2009 and since then it spread worldwide over a short period of time. Although the virus infection is generally associated with mild disease and a relatively low mortality, it is projected that mutations in specific regions of the viral genome, especially within the receptor binding domain of the haemagglutinin (HA) protein could result in more virulent virus stains, leading to a more severe pathogenicity. METHODS: To monitor the genetic polymorphisms at position 222 of Haemagglutinin of influenza A(H1N1)pdm09 viruses from both outpatients with mild influenza and individuals with severe disease requiring hospitalization, during 2009–2010 and 2010–2011 seasons, a sequence-based genotypic assessment of viral populations to understand the prevalence of D222G mutation. RESULTS: The D222G was identified in clinical specimens from 3 out of 42 cases analyzed in Tunisia with severe outcome (7%). Interestingly, in one fatal case out of four viruses taken from fatal cases studied (25%). Also this mutation was found in one mild case out of 8 mild cases studied (0.1%). D222E substitution was found in virus taken from one patient with severe clinical syndrome (2%) out of 42 severe cases analyzed and E374K substitution was found in two severe cases (4%) out of 42 severe cases studied. CONCLUSIONS: A specific mutation in the viral haemagglutinin (D222G) was found in fatal, severe and mild case. Further virological, clinical and epidemiological investigations are needed to ascertain the role of this and other mutations that may alter the virulence and transmissibility of the pandemic influenza A (H1N1)pdm09. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1027334947811255",2013 Jul 31,"['Moussi, Awatef El', 'Kacem, Mohamed Ali Ben Hadj', 'Pozo, Francisco', 'Ledesma, Juan', 'Cuevas, Maria Teresa', 'Casas, Inmaculada', 'Slim, Amine']",Diagn Pathol,,,True
b0022167496e4388b198ab691103ffe066e0c9cc,PMC,Complete Genome Sequence Analysis of a Reassortant Strain of Bluetongue Virus Serotype 16 from Italy,http://dx.doi.org/10.1128/genomeA.00622-13,PMC3751604,23969049,CC BY,"The complete genome sequence of a reassortant field strain of bluetongue virus serotype 16 (BTV-16), isolated from cattle in the Apulia region of Italy in 2002, has been determined by Illumina sequencing. Sequence comparisons of segment 1 (Seg-1) to Seg-10, except Seg-5, show that BTV-16 strain ITL2002 belongs to the major eastern topotype of BTV.",2013 Aug 22,"['Lorusso, Alessio', 'Costessi, Adalberto', 'Pirovano, Walter', 'Marcacci, Maurilia', 'Cammà, Cesare', 'Savini, Giovanni']",Genome Announc,,,True
bab3d2a212eaf7740a45ee8efeec3db99bf94589,PMC,"Complete Genome Sequence of a Very Virulent Porcine Epidemic Diarrhea Virus Strain, CH/GDGZ/2012, Isolated in Southern China",http://dx.doi.org/10.1128/genomeA.00645-13,PMC3751607,23969052,CC BY,"The classical symptoms of porcine epidemic diarrhea (PED) are acute diarrhea and dehydration. The isolated porcine epidemic diarrhea virus (PEDV) CH/GDGZ/2012 strain was obtained from the feces of diseased pigs in 2012 in southern China. We report the complete genome sequence of strain CH/GDGZ/2012, which might be useful for better understanding the molecular characteristics of this virus.",2013 Aug 22,"['Tian, Ye', 'Su, Danping', 'Zhang, Haiming', 'Chen, Rui-ai', 'He, Dongsheng']",Genome Announc,,,True
ffe7169e14eea9af001ae388632123d43eeb9697,PMC,Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection,http://dx.doi.org/10.1186/1471-2172-14-40,PMC3751766,23947615,CC BY,"BACKGROUND: Some studies have shown that nasally administered immunobiotics had the potential to improve the outcome of influenza virus infection. However, the capacity of immunobiotics to improve protection against respiratory syncytial virus (RSV) infection was not investigated before. OBJECTIVE: The aims of this study were: a) to evaluate whether the nasal administration of Lactobacillus rhamnosus CRL1505 (Lr05) and L. rhamnosus CRL1506 (Lr06) are able to improve respiratory antiviral defenses and beneficially modulate the immune response triggered by TLR3/RIG-I activation; b) to investigate whether viability of Lr05 or Lr06 is indispensable to modulate respiratory immunity and; c) to evaluate the capacity of Lr05 and Lr06 to improve the resistance of infant mice against RSV infection. RESULTS: Nasally administered Lr05 and Lr06 differentially modulated the TLR3/RIG-I-triggered antiviral respiratory immune response. Lr06 administration significantly modulated the production of IFN-α, IFN-β and IL-6 in the response to poly(I:C) challenge, while nasal priming with Lr05 was more effective to improve levels of IFN-γ and IL-10. Both viable Lr05 and Lr06 strains increased the resistance of infant mice to RSV infection while only heat-killed Lr05 showed a protective effect similar to those observed with viable strains. CONCLUSIONS: The present work demonstrated that nasal administration of immunobiotics is able to beneficially modulate the immune response triggered by TLR3/RIG-I activation in the respiratory tract and to increase the resistance of mice to the challenge with RSV. Comparative studies using two Lactobacillus rhamnosus strains of the same origin and with similar technological properties showed that each strain has an specific immunoregulatory effect in the respiratory tract and that they differentially modulate the immune response after poly(I:C) or RSV challenges, conferring different degree of protection and using distinct immune mechanisms. We also demonstrated in this work that it is possible to beneficially modulate the respiratory defenses against RSV by using heat-killed immunobiotics.",2013 Aug 15,"['Tomosada, Yohsuke', 'Chiba, Eriko', 'Zelaya, Hortensia', 'Takahashi, Takuya', 'Tsukida, Kohichiro', 'Kitazawa, Haruki', 'Alvarez, Susana', 'Villena, Julio']",BMC Immunol,,,True
76b1bad1aba249a858d1112096bbc4fbf3ae7d5d,PMC,Inhibition of hepatitis B virus (HBV) gene expression and replication by HBx gene silencing in a hydrodynamic injection mouse model with a new clone of HBV genotype B,http://dx.doi.org/10.1186/1743-422X-10-214,PMC3751867,23805945,CC BY,"BACKGROUND: It has been suggested that different hepatitis B virus (HBV) genotypes may have distinct virological characteristics that correlate with clinical outcomes during antiviral therapy and the natural course of infection. Hydrodynamic injection (HI) of HBV in the mouse model is a useful tool for study of HBV replication in vivo. However, only HBV genotype A has been used for studies with HI. METHODS: We constructed 3 replication-competent clones containing 1.1, 1.2 and 1.3 fold overlength of a HBV genotype B genome and tested them both in vitro and in vivo. Moreover, A HBV genotype B clone based on the pAAV-MCS vector was constructed with the 1.3 fold HBV genome, resulting in the plasmid pAAV-HBV1.3(B) and tested by HI in C57BL/6 mice. Application of siRNA against HBx gene was tested in HBV genotype B HI mouse model. RESULTS: The 1.3 fold HBV clone showed higher replication and gene expression than the 1.1 and 1.2 fold HBV clones. Compared with pAAV-HBV1.2 (genotype A), the mice HI with pAAV-HBV1.3(B) showed higher HBsAg and HBeAg expression as well as HBV DNA replication level but a higher clearance rate. Application of two plasmids pSB-HBxi285 and pSR-HBxi285 expressing a small/short interfering RNA (siRNA) to the HBx gene in HBV genotype B HI mouse model, leading to an inhibition of HBV gene expression and replication. However, HBV gene expression may resume in some mice despite an initial delay, suggesting that transient suppression of HBV replication by siRNA may be insufficient to prevent viral spread, particularly if the gene silencing is not highly effective. CONCLUSIONS: Taken together, the HI mouse model with a HBV genotype B genome was successfully established and showed different characteristics in vivo compared with the genotype A genome. The effectiveness of gene silencing against HBx gene determines whether HBV replication may be sustainably inhibited by siRNA in vivo.",2013 Jun 28,"['Li, Lei', 'Shen, Hong', 'Li, Anyi', 'Zhang, Zhenhua', 'Wang, Baoju', 'Wang, Junzhong', 'Zheng, Xin', 'Wu, Jun', 'Yang, Dongliang', 'Lu, Mengji', 'Song, Jingjiao']",Virol J,,,True
0d6a162406af842f2324077d73de17b2e85cffdb,PMC,Comparative Evaluation of Six Commercialized Multiplex PCR Kits for the Diagnosis of Respiratory Infections,http://dx.doi.org/10.1371/journal.pone.0072174,PMC3751960,24058410,CC BY,"The molecular diagnosis of respiratory infection can be performed using different commercial multiplex-based PCR kits whose performances have been previously compared individually to those of conventional techniques. This study compared the practicability and the diagnostic performances of six CE-marked kits available in 2011 on the French market, including 2 detecting viruses and atypical bacteria (from Pathofinder and Seegene companies) and 4 detecting only viruses (from Abbott, Genomica, Qiagen and Seegene companies). The respective sensitivity, specificity, accuracy and agreement of each multiplex technique were calculated by comparison to commercial duplex PCR tests (Argene/bioMérieux) used as gold standard. Eighty-eight respiratory specimens with no pathogen (n = 11), single infections (n = 33) or co-infections (n = 44) were selected to cover 9 viruses or groups of viruses and 3 atypical bacteria. All samples were extracted using the NUCLISENS® easyMAG™ instrument (bioMérieux). The overall sensitivity ranged from 56.25% to 91.67% for viruses and was below 50% with both tests for bacteria. The overall specificity was excellent (>94% for all pathogens). For each tested kit, the overall agreement with the reference test was strong for viruses (kappa test >0.60) and moderate for bacteria. After the extraction step, the hands-on time varied from 50 min to 2h30 and the complete results were available in 2h30 to 9 h. The spectrum of tested agents and the technology used to reveal the PCR products as well as the laboratory organization are determinant for the selection of a kit.",2013 Aug 23,"['Pillet, Sylvie', 'Lardeux, Marina', 'Dina, Julia', 'Grattard, Florence', 'Verhoeven, Paul', 'Le Goff, Jérôme', 'Vabret, Astrid', 'Pozzetto, Bruno']",PLoS One,,,True
9ce462cb0807906c475d4b600afac950c7e8c4e8,PMC,Get the News Out Loudly and Quickly: The Influence of the Media on Limiting Emerging Infectious Disease Outbreaks,http://dx.doi.org/10.1371/journal.pone.0071692,PMC3753329,23990974,CC BY,"During outbreaks of infectious diseases with high morbidity and mortality, individuals closely follow media reports of the outbreak. Many will attempt to minimize contacts with other individuals in order to protect themselves from infection and possibly death. This process is called social distancing. Social distancing strategies include restricting socializing and travel, and using barrier protections. We use modeling to show that for short-term outbreaks, social distancing can have a large influence on reducing outbreak morbidity and mortality. In particular, public health agencies working together with the media can significantly reduce the severity of an outbreak by providing timely accounts of new infections and deaths. Our models show that the most effective strategy to reduce infections is to provide this information as early as possible, though providing it well into the course of the outbreak can still have a significant effect. However, our models for long-term outbreaks indicate that reporting historic infection data can result in more infections than with no reporting at all. We examine three types of media influence and we illustrate the media influence with a simulated outbreak of a generic emerging infectious disease in a small city. Social distancing can never be complete; however, for a spectrum of outbreaks, we show that leaving isolation (stopping applying social distancing measures) for up to 4 hours each day has modest effect on the overall morbidity and mortality.",2013 Aug 26,"['Mummert, Anna', 'Weiss, Howard']",PLoS One,,,True
462a0562fd2597131766176ce8f001ada8728a91,PMC,Get the News Out Loudly and Quickly: The Influence of the Media on Limiting Emerging Infectious Disease Outbreaks,http://dx.doi.org/10.1371/journal.pone.0071692,PMC3753329,23990974,CC BY,"During outbreaks of infectious diseases with high morbidity and mortality, individuals closely follow media reports of the outbreak. Many will attempt to minimize contacts with other individuals in order to protect themselves from infection and possibly death. This process is called social distancing. Social distancing strategies include restricting socializing and travel, and using barrier protections. We use modeling to show that for short-term outbreaks, social distancing can have a large influence on reducing outbreak morbidity and mortality. In particular, public health agencies working together with the media can significantly reduce the severity of an outbreak by providing timely accounts of new infections and deaths. Our models show that the most effective strategy to reduce infections is to provide this information as early as possible, though providing it well into the course of the outbreak can still have a significant effect. However, our models for long-term outbreaks indicate that reporting historic infection data can result in more infections than with no reporting at all. We examine three types of media influence and we illustrate the media influence with a simulated outbreak of a generic emerging infectious disease in a small city. Social distancing can never be complete; however, for a spectrum of outbreaks, we show that leaving isolation (stopping applying social distancing measures) for up to 4 hours each day has modest effect on the overall morbidity and mortality.",2013 Aug 26,"['Mummert, Anna', 'Weiss, Howard']",PLoS One,,,False
b55409d93e144178d64a7a39b46e4b160f8d03a5,PMC,Get the News Out Loudly and Quickly: The Influence of the Media on Limiting Emerging Infectious Disease Outbreaks,http://dx.doi.org/10.1371/journal.pone.0071692,PMC3753329,23990974,CC BY,"During outbreaks of infectious diseases with high morbidity and mortality, individuals closely follow media reports of the outbreak. Many will attempt to minimize contacts with other individuals in order to protect themselves from infection and possibly death. This process is called social distancing. Social distancing strategies include restricting socializing and travel, and using barrier protections. We use modeling to show that for short-term outbreaks, social distancing can have a large influence on reducing outbreak morbidity and mortality. In particular, public health agencies working together with the media can significantly reduce the severity of an outbreak by providing timely accounts of new infections and deaths. Our models show that the most effective strategy to reduce infections is to provide this information as early as possible, though providing it well into the course of the outbreak can still have a significant effect. However, our models for long-term outbreaks indicate that reporting historic infection data can result in more infections than with no reporting at all. We examine three types of media influence and we illustrate the media influence with a simulated outbreak of a generic emerging infectious disease in a small city. Social distancing can never be complete; however, for a spectrum of outbreaks, we show that leaving isolation (stopping applying social distancing measures) for up to 4 hours each day has modest effect on the overall morbidity and mortality.",2013 Aug 26,"['Mummert, Anna', 'Weiss, Howard']",PLoS One,,,False
55d1bc868ea9e1d565c85b250aa7195b95c80f43,PMC,Get the News Out Loudly and Quickly: The Influence of the Media on Limiting Emerging Infectious Disease Outbreaks,http://dx.doi.org/10.1371/journal.pone.0071692,PMC3753329,23990974,CC BY,"During outbreaks of infectious diseases with high morbidity and mortality, individuals closely follow media reports of the outbreak. Many will attempt to minimize contacts with other individuals in order to protect themselves from infection and possibly death. This process is called social distancing. Social distancing strategies include restricting socializing and travel, and using barrier protections. We use modeling to show that for short-term outbreaks, social distancing can have a large influence on reducing outbreak morbidity and mortality. In particular, public health agencies working together with the media can significantly reduce the severity of an outbreak by providing timely accounts of new infections and deaths. Our models show that the most effective strategy to reduce infections is to provide this information as early as possible, though providing it well into the course of the outbreak can still have a significant effect. However, our models for long-term outbreaks indicate that reporting historic infection data can result in more infections than with no reporting at all. We examine three types of media influence and we illustrate the media influence with a simulated outbreak of a generic emerging infectious disease in a small city. Social distancing can never be complete; however, for a spectrum of outbreaks, we show that leaving isolation (stopping applying social distancing measures) for up to 4 hours each day has modest effect on the overall morbidity and mortality.",2013 Aug 26,"['Mummert, Anna', 'Weiss, Howard']",PLoS One,,,False
95ee3b41047edd02d74ab869375f1dcb7b83c31c,PMC,Co-expression of RNA–protein complexes in Escherichia coli and applications to RNA biology,http://dx.doi.org/10.1093/nar/gkt576,PMC3753655,23804766,CC BY,"RNA has emerged as a major player in many cellular processes. Understanding these processes at the molecular level requires homogeneous RNA samples for structural, biochemical and pharmacological studies. We previously devised a generic approach that allows efficient in vivo expression of recombinant RNA in Escherichia coli. In this work, we have extended this method to RNA/protein co-expression. We have engineered several plasmids that allow overexpression of RNA–protein complexes in E. coli. We have investigated the potential of these tools in many applications, including the production of nuclease-sensitive RNAs encapsulated in viral protein pseudo-particles, the co-production of non-coding RNAs with chaperone proteins, the incorporation of a post-transcriptional RNA modification by co-production with the appropriate modifying enzyme and finally the production and purification of an RNA–His-tagged protein complex by nickel affinity chromatography. We show that this last application easily provides pure material for crystallographic studies. The new tools we report will pave the way to large-scale structural and molecular investigations of RNA function and interactions with proteins.",2013 Aug 25,"['Ponchon, Luc', 'Catala, Marjorie', 'Seijo, Bili', 'El Khouri, Marguerite', 'Dardel, Frédéric', 'Nonin-Lecomte, Sylvie', 'Tisné, Carine']",Nucleic Acids Res,,,True
d604b2fa9328520de1cb77b550803b82b6bbbe87,PMC,Duplex Molecular Assay Intended for Point-of-Care Diagnosis of Influenza A/B Virus Infection,http://dx.doi.org/10.1128/JCM.00740-13,PMC3754654,23850955,CC BY,"Early diagnosis and management of influenza virus infection directly correlates with the effectiveness in disease control. Current molecular influenza virus tests were designed for use in diagnostic testing facilities, where sophisticated equipment and highly trained technicians are available. A longer turnaround time for the centralized testing than when testing near the sample source could delay the initiation of medical intervention, thereby reducing the efficacy of antiviral treatment. The new assay, the SAMBA (simple amplification-based assay) Flu duplex test, is a dipstick-based molecular assay developed to provide a simple, accurate, and cost-effective solution for the diagnosis of influenza A/B viruses intended for near-patient testing. The test presents an alternative format of influenza virus molecular testing that utilizes isothermal amplification and visual detection of nucleic acid on a test strip. The entire test procedure (extraction, amplification, and detection) is integrated into an enclosed semiautomated system. Analytically, the SAMBA Flu duplex test detects 95 and 85 copies of viral genomes for influenza A and B viruses, respectively, with no cross-reactivity observed against other common respiratory pathogens. The clinical performance was established by blind testing of 328 nasal/throat and nasopharyngeal swab specimens from the United Kingdom and Belgium and comparing the results with the quantitative reverse transcription-PCR method routinely used in two public health laboratories. The SAMBA Flu duplex test showed a clinical sensitivity and specificity of 100% and 97.9% for influenza virus A and 100% and 100% for influenza virus B. The test provides a new technology that could facilitate simple and timely identification of influenza virus infection, potentially resulting in more efficient control measures.",2013 Sep,"['Wu, Liang-Ta', 'Thomas, Isabelle', 'Curran, Martin D.', 'Ellis, Joanna S.', 'Parmar, Surendra', 'Goel, Neha', 'Sharma, Pia I.', 'Allain, Jean-Pierre', 'Lee, Helen H.']",J Clin Microbiol,,,True
06c172a11ee30931ac537dfb70ce020dced50918,PMC,"The Mongoose, the Pheasant, the Pox, and the Retrovirus",http://dx.doi.org/10.1371/journal.pbio.1001641,PMC3754884,24013523,CC BY,"Paleovirology is the study of ancient viruses. The existence of a paleovirus can sometimes be detected by virtue of its accidental insertion into the germline of different animal species, which allows one to date when the virus actually existed. However, the ancient and the modern often connect, as modern viruses have unexpected origins that can be traced to ancient infections. The genomes of two species of mongooses and an egg-laying mammal called an echidna show that a virus currently present in poultry, the reticuloendotheliosis virus (REV), is actually of ancient exotic mammalian origin. REV apparently spread to poultry through a circuitous route involving the isolation of malaria parasites from a pheasant from Borneo housed at the Bronx Zoo that was contaminated with REV. Repeated passage of this virus in poultry adapted the virus to its new host. At some point, the virus got inserted into another virus, called fowlpox virus, which has spread back into the wild. Although REV may still exist somewhere in a mammalian host, its modern form links an 8 million-year-old infection of the ancestor of a mongoose to a virus that now is circulating in wild birds through malaria studies in the mid-20(th) century. These lessons of ancient and modern viruses have implications for modern human pandemics from viral reservoirs and for human interventions that may come with unintended consequences.",2013 Aug 27,"['Etienne, Lucie', 'Emerman, Michael']",PLoS Biol,,,True
db7b6440cfdfd2bbf71c22361d4ea606a16d4643,PMC,iGPCR-Drug: A Web Server for Predicting Interaction between GPCRs and Drugs in Cellular Networking,http://dx.doi.org/10.1371/journal.pone.0072234,PMC3754978,24015221,CC BY,"Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs) are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional) structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called “iGPCR-drug”, was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional) fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition) generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug – target interaction networks.",2013 Aug 27,"['Xiao, Xuan', 'Min, Jian-Liang', 'Wang, Pu', 'Chou, Kuo-Chen']",PLoS One,,,True
b47bbf9315d63e713950bc5b5c15f9299411cc9f,PMC,iGPCR-Drug: A Web Server for Predicting Interaction between GPCRs and Drugs in Cellular Networking,http://dx.doi.org/10.1371/journal.pone.0072234,PMC3754978,24015221,CC BY,"Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs) are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional) structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called “iGPCR-drug”, was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional) fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition) generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug – target interaction networks.",2013 Aug 27,"['Xiao, Xuan', 'Min, Jian-Liang', 'Wang, Pu', 'Chou, Kuo-Chen']",PLoS One,,,False
cb9ca284ea7badccc5e93a2c3f5eb2f34598aecb,PMC,iGPCR-Drug: A Web Server for Predicting Interaction between GPCRs and Drugs in Cellular Networking,http://dx.doi.org/10.1371/journal.pone.0072234,PMC3754978,24015221,CC BY,"Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs) are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional) structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called “iGPCR-drug”, was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional) fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition) generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug – target interaction networks.",2013 Aug 27,"['Xiao, Xuan', 'Min, Jian-Liang', 'Wang, Pu', 'Chou, Kuo-Chen']",PLoS One,,,False
de88e6c770596c1e10e37b72c6303490d03ede05,PMC,iGPCR-Drug: A Web Server for Predicting Interaction between GPCRs and Drugs in Cellular Networking,http://dx.doi.org/10.1371/journal.pone.0072234,PMC3754978,24015221,CC BY,"Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs) are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional) structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called “iGPCR-drug”, was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional) fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition) generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug – target interaction networks.",2013 Aug 27,"['Xiao, Xuan', 'Min, Jian-Liang', 'Wang, Pu', 'Chou, Kuo-Chen']",PLoS One,,,False
6f251e71a441068ffe96970bf5d857713ec30163,PMC,Modulation of Protease Activated Receptor 1 Influences Human Metapneumovirus Disease Severity in a Mouse Model,http://dx.doi.org/10.1371/journal.pone.0072529,PMC3755973,24015257,CC BY,"Human metapneumovirus (hMPV) infection causes acute respiratory tract infections (RTI) which can result in hospitalization of both children and adults. To date, no antiviral or vaccine is available for this common viral infection. Immunomodulators could represent an interesting strategy for the treatment of severe viral infection. Recently, the role of protease-activated receptors (PAR) in inflammation, coagulation and infection processes has been of growing interest. Herein, the effects of a PAR1 agonist and a PAR1 antagonist on hMPV infection were investigated in BALB/c mice. Intranasal administration of the PAR1 agonist resulted in increased weight loss and mortality of infected mice. Conversely, the PAR1 antagonist was beneficial to hMPV infection by decreasing weight loss and clinical signs and by significantly reducing pulmonary inflammation, pro-inflammatory cytokine levels (including IL-6, KC and MCP-1) and recruitment of immune cells to the lungs. In addition, a significant reduction in pulmonary viral titers was also observed in the lungs of PAR1 antagonist-treated mice. Despite no apparent direct effect on virus replication during in vitro experiments, an important role for PAR1 in the regulation of furin expression in the lungs was shown for the first time. Further experiments indicated that the hMPV fusion protein can be cleaved by furin thus suggesting that PAR1 could have an effect on viral infectivity in addition to its immunomodulatory properties. Thus, inhibition of PAR1 by selected antagonists could represent an interesting strategy for decreasing the severity of paramyxovirus infections.",2013 Aug 28,"['Aerts, Laetitia', 'Hamelin, Marie-Ève', 'Rhéaume, Chantal', 'Lavigne, Sophie', 'Couture, Christian', 'Kim, WooJin', 'Susan-Resiga, Delia', 'Prat, Annik', 'Seidah, Nabil G.', 'Vergnolle, Nathalie', 'Riteau, Beatrice', 'Boivin, Guy']",PLoS One,,,True
5b029e946adb1adaf73c953ca02413da64fc6c53,PMC,Use of a Small Peptide Fragment as an Inhibitor of Insulin Fibrillation Process: A Study by High and Low Resolution Spectroscopy,http://dx.doi.org/10.1371/journal.pone.0072318,PMC3756998,24009675,CC BY,"A non-toxic, nine residue peptide, NIVNVSLVK is shown to interfere with insulin fibrillation by various biophysical methods. Insulin undergoes conformational changes under certain stress conditions leading to amyloid fibrils. Fibrillation of insulin poses a problem in its long-term storage, reducing its efficacy in treating type II diabetes. The dissociation of insulin oligomer to monomer is the key step for the onset of fibrillation. The time course of insulin fibrillation at 62°C using Thioflavin T fluorescence shows an increase in the lag time from 120 min without peptide to 236 min with peptide. Transmission electron micrographs show branched insulin fibrils in its absence and less inter-fibril association in its presence. Upon incubation at 62°C and pH 2.6, insulin lost some α-helical structure as seen by Fourier transformed infra-red spectroscopy (FT-IR), but if the peptide is added, secondary structure is almost fully maintained for 3 h, though lost partially at 4 h. FT-IR spectroscopy also shows that insulin forms the cross beta structure indicative of fibrils beyond 2 h, but in the presence of the peptide, α-helix retention is seen till 4 h. Both size exclusion chromatography and dynamic light scattering show that insulin primarily exists as trimer, whose conversion to a monomer is resisted by the peptide. Saturation transfer difference nuclear magnetic resonance confirms that the hydrophobic residues in the peptide are in close contact with an insulin hydrophobic groove. Molecular dynamics simulations in conjunction with principal component analyses reveal how the peptide interrupts insulin fibrillation. In vitro hemolytic activity of the peptide showed insignificant cytotoxicity against HT1080 cells. The insulin aggregation is probed due to the inter play of two key residues, Phe(B24) and Tyr(B26) monitored from molecular dynamics simulations studies. Further new peptide based leads may be developed from this nine residue peptide.",2013 Aug 29,"['Banerjee, Victor', 'Kar, Rajiv K.', 'Datta, Aritreyee', 'Parthasarathi, Krupakar', 'Chatterjee, Subhrangsu', 'Das, Kali P.', 'Bhunia, Anirban']",PLoS One,,,True
63f776d8ae5084cc5a3aa5e09aa55f1a302b1b1f,PMC,Identification and Survey of a Novel Avian Coronavirus in Ducks,http://dx.doi.org/10.1371/journal.pone.0072918,PMC3758261,24023656,CC BY,"The rapid discovery of novel viruses using next generation sequencing (NGS) technologies including DNA-Seq and RNA-Seq, has greatly expanded our understanding of viral diversity in recent years. The timely identification of novel viruses using NGS technologies is also important for us to control emerging infectious diseases caused by novel viruses. In this study, we identified a novel duck coronavirus (CoV), distinct with chicken infectious bronchitis virus (IBV), using RNA-Seq. The novel duck-specific CoV was a potential novel species within the genus Gammacoronavirus, as indicated by sequences of three regions in the viral 1b gene. We also performed a survey of CoVs in domestic fowls in China using reverse-transcription polymerase chain reaction (RT-PCR), targeting the viral nucleocapsid (N) gene. A total of 102 CoV positives were identified through the survey. Phylogenetic analysis of the viral N sequences suggested that CoVs in domestic fowls have diverged into several region-specific or host-specific clades or subclades in the world, and IBVs can infect ducks, geese and pigeons, although they mainly circulate in chickens. Moreover, this study provided novel data supporting the notion that some host-specific CoVs other than IBVs circulate in ducks, geese and pigeons, and indicated that the novel duck-specific CoV identified through RNA-Seq in this study is genetically closer to some CoVs circulating in wild water fowls. Taken together, this study shed new insight into the diversity, distribution, evolution and control of avian CoVs.",2013 Aug 30,"['Chen, Gui-Qian', 'Zhuang, Qing-Ye', 'Wang, Kai-Cheng', 'Liu, Shuo', 'Shao, Jian-Zhong', 'Jiang, Wen-Ming', 'Hou, Guang-Yu', 'Li, Jin-Ping', 'Yu, Jian-Min', 'Li, Yi-Ping', 'Chen, Ji-Ming']",PLoS One,,,True
b2fde3b77f54db50b124bca17aaba10069e4424b,PMC,Estimating a Markovian Epidemic Model Using Household Serial Interval Data from the Early Phase of an Epidemic,http://dx.doi.org/10.1371/journal.pone.0073420,PMC3758268,24023679,CC BY,"The clinical serial interval of an infectious disease is the time between date of symptom onset in an index case and the date of symptom onset in one of its secondary cases. It is a quantity which is commonly collected during a pandemic and is of fundamental importance to public health policy and mathematical modelling. In this paper we present a novel method for calculating the serial interval distribution for a Markovian model of household transmission dynamics. This allows the use of Bayesian MCMC methods, with explicit evaluation of the likelihood, to fit to serial interval data and infer parameters of the underlying model. We use simulated and real data to verify the accuracy of our methodology and illustrate the importance of accounting for household size. The output of our approach can be used to produce posterior distributions of population level epidemic characteristics.",2013 Aug 30,"['Black, Andrew J.', 'Ross, Joshua V.']",PLoS One,,,True
33e9e969d555d597b3af0d6c4bdb38010ce3996d,PMC,Estimating a Markovian Epidemic Model Using Household Serial Interval Data from the Early Phase of an Epidemic,http://dx.doi.org/10.1371/journal.pone.0073420,PMC3758268,24023679,CC BY,"The clinical serial interval of an infectious disease is the time between date of symptom onset in an index case and the date of symptom onset in one of its secondary cases. It is a quantity which is commonly collected during a pandemic and is of fundamental importance to public health policy and mathematical modelling. In this paper we present a novel method for calculating the serial interval distribution for a Markovian model of household transmission dynamics. This allows the use of Bayesian MCMC methods, with explicit evaluation of the likelihood, to fit to serial interval data and infer parameters of the underlying model. We use simulated and real data to verify the accuracy of our methodology and illustrate the importance of accounting for household size. The output of our approach can be used to produce posterior distributions of population level epidemic characteristics.",2013 Aug 30,"['Black, Andrew J.', 'Ross, Joshua V.']",PLoS One,,,True
4903f4b49cff9b009f9413ae245ecb75bd97960c,PMC,"Differential Sensitivity of Bat Cells to Infection by Enveloped RNA Viruses: Coronaviruses, Paramyxoviruses, Filoviruses, and Influenza Viruses",http://dx.doi.org/10.1371/journal.pone.0072942,PMC3758312,24023659,CC BY,"Bats (Chiroptera) host major human pathogenic viruses including corona-, paramyxo, rhabdo- and filoviruses. We analyzed six different cell lines from either Yinpterochiroptera (including African flying foxes and a rhinolophid bat) or Yangochiroptera (genera Carollia and Tadarida) for susceptibility to infection by different enveloped RNA viruses. None of the cells were sensitive to infection by transmissible gastroenteritis virus (TGEV), a porcine coronavirus, or to infection mediated by the Spike (S) protein of SARS-coronavirus (SARS-CoV) incorporated into pseudotypes based on vesicular stomatitis virus (VSV). The resistance to infection was overcome if cells were transfected to express the respective cellular receptor, porcine aminopeptidase N for TGEV or angiotensin-converting enzyme 2 for SARS-CoV. VSV pseudotypes containing the S proteins of two bat SARS-related CoV (Bg08 and Rp3) were unable to infect any of the six tested bat cell lines. By contrast, viral pseudotypes containing the surface protein GP of Marburg virus from the family Filoviridae infected all six cell lines though at different efficiency. Notably, all cells were sensitive to infection by two paramyxoviruses (Sendai virus and bovine respiratory syncytial virus) and three influenza viruses from different subtypes. These results indicate that bat cells are more resistant to infection by coronaviruses than to infection by paramyxoviruses, filoviruses and influenza viruses. Furthermore, these results show a receptor-dependent restriction of the infection of bat cells by CoV. The implications for the isolation of coronaviruses from bats are discussed.",2013 Aug 30,"['Hoffmann, Markus', 'Müller, Marcel Alexander', 'Drexler, Jan Felix', 'Glende, Jörg', 'Erdt, Meike', 'Gützkow, Tim', 'Losemann, Christoph', 'Binger, Tabea', 'Deng, Hongkui', 'Schwegmann-Weßels, Christel', 'Esser, Karl-Heinz', 'Drosten, Christian', 'Herrler, Georg']",PLoS One,,,True
a71052d0d97adb979510b675275149d05cd7976e,PMC,Assessment of the Evolution of Cancer Treatment Therapies,http://dx.doi.org/10.3390/cancers3033279,PMC3759197,24212956,CC BY,"Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.",2011 Aug 12,"['Arruebo, Manuel', 'Vilaboa, Nuria', 'Sáez-Gutierrez, Berta', 'Lambea, Julio', 'Tres, Alejandro', 'Valladares, Mónica', 'González-Fernández, África']",Cancers (Basel),,,True
443aa07a6f57cab4c25fcdb0add50527028d6769,PMC,Emerging Cancer Vaccines: The Promise of Genetic Vectors,http://dx.doi.org/10.3390/cancers3033687,PMC3759217,24212974,CC BY,"Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost.",2011 Sep 22,"['Aurisicchio, Luigi', 'Ciliberto, Gennaro']",Cancers (Basel),,,True
946087e7d17c7256e8c90187ee7d27f3df870919,PMC,Asymmetry of Cell Division in CFSE-Based Lymphocyte Proliferation Analysis,http://dx.doi.org/10.3389/fimmu.2013.00264,PMC3759284,24032033,CC BY,"Flow cytometry-based analysis of lymphocyte division using carboxyfluorescein succinimidyl ester (CFSE) dye dilution permits acquisition of data describing cellular proliferation and differentiation. For example, CFSE histogram data enable quantitative insight into cellular turnover rates by applying mathematical models and parameter estimation techniques. Several mathematical models have been developed using different types of deterministic or stochastic approaches. However, analysis of CFSE proliferation assays is based on the premise that the label is halved in the two daughter cells. Importantly, asymmetry of protein distribution in lymphocyte division is a basic biological feature of cell division with the degree of the asymmetry depending on various factors. Here, we review the recent literature on asymmetric lymphocyte division and CFSE-based lymphocyte proliferation analysis. We suggest that division- and label-structured mathematical models describing CFSE-based cell proliferation should take into account asymmetry and time-lag in cell proliferation. Utilization of improved modeling algorithms will permit straightforward quantification of essential parameters describing the performance of activated lymphocytes.",2013 Sep 2,"['Bocharov, Gennady', 'Luzyanina, Tatyana', 'Cupovic, Jovana', 'Ludewig, Burkhard']",Front Immunol,,,True
e24a0cd976fbe3f6a625425e6c9899d52af1067f,PMC,Sialic Acid Binding Properties of Soluble Coronavirus Spike (S1) Proteins: Differences between Infectious Bronchitis Virus and Transmissible Gastroenteritis Virus,http://dx.doi.org/10.3390/v5081924,PMC3761233,23896748,CC BY,"The spike proteins of a number of coronaviruses are able to bind to sialic acids present on the cell surface. The importance of this sialic acid binding ability during infection is, however, quite different. We compared the spike protein of transmissible gastroenteritis virus (TGEV) and the spike protein of infectious bronchitis virus (IBV). Whereas sialic acid is the only receptor determinant known so far for IBV, TGEV requires interaction with its receptor aminopeptidase N to initiate infection of cells. Binding tests with soluble spike proteins carrying an IgG Fc-tag revealed pronounced differences between these two viral proteins. Binding of the IBV spike protein to host cells was in all experiments sialic acid dependent, whereas the soluble TGEV spike showed binding to APN but had no detectable sialic acid binding activity. Our results underline the different ways in which binding to sialoglycoconjugates is mediated by coronavirus spike proteins.",2013 Jul 26,"['Shahwan, Katarina', 'Hesse, Martina', 'Mork, Ann-Kathrin', 'Herrler, Georg', 'Winter, Christine']",Viruses,,,True
d92d26c41ab17c1cf0bea776233045118ffecb84,PMC,"Molecular Characterization and Phylogenetic Analysis of New Variants of the Porcine Epidemic Diarrhea Virus in Gansu, China in 2012",http://dx.doi.org/10.3390/v5081991,PMC3761238,23955500,CC BY,"Between January 2012 and March 2012, the infection rates of porcine epidemic diarrhea virus (PEDV) increased substantially in vaccinated swine herds in many porcine farms in Gansu Province, China. The spike (S) glycoprotein is an important determinant for PEDV biological properties. To determine the distribution profile of PEDV outbreak strains, we sequenced the full-length S gene of five samples from two farms where animals exhibited severe diarrhea and high mortality rates. Five new PEDV variants were identified, and the molecular diversity, phylogenetic relationships, and antigenicity analysis of Gansu field samples with other PEDV reference strains were investigated. A series of insertions, deletions, and mutations in the S gene was found in five PEDV variants compared with classical and vaccine strains. These mutations may provide stronger pathogenicity and antigenicity to the new PEDV variants that influenced the effectiveness of the CV777-based vaccine. Our results suggest that these new PEDV variant strains in Gansu Province might be from South Korean or South China, and the effectiveness of the CV777-based vaccine needs to be evaluated.",2013 Aug 15,"['Tian, Yufei', 'Yu, Zhijun', 'Cheng, Kaihui', 'Liu, Yuxiu', 'Huang, Jing', 'Xin, Yue', 'Li, Yuanguo', 'Fan, Shengtao', 'Wang, Tiecheng', 'Huang, Geng', 'Feng, Na', 'Yang, Zhenguo', 'Yang, Songtao', 'Gao, Yuwei', 'Xia, Xianzhu']",Viruses,,,True
b786e66932955124f073e42aec53ea4a0f0cbb9b,PMC,Global Causes of Diarrheal Disease Mortality in Children <5 Years of Age: A Systematic Review,http://dx.doi.org/10.1371/journal.pone.0072788,PMC3762858,24023773,CC0,"Estimation of pathogen-specific causes of child diarrhea deaths is needed to guide vaccine development and other prevention strategies. We did a systematic review of articles published between 1990 and 2011 reporting at least one of 13 pathogens in children <5 years of age hospitalized with diarrhea. We included 2011 rotavirus data from the Rotavirus Surveillance Network coordinated by WHO. We excluded studies conducted during diarrhea outbreaks that did not discriminate between inpatient and outpatient cases, reporting nosocomial infections, those conducted in special populations, not done with adequate methods, and rotavirus studies in countries where the rotavirus vaccine was used. Age-adjusted median proportions for each pathogen were calculated and applied to 712 000 deaths due to diarrhea in children under 5 years for 2011, assuming that those observed among children hospitalized for diarrhea represent those causing child diarrhea deaths. 163 articles and WHO studies done in 31 countries were selected representing 286 inpatient studies. Studies seeking only one pathogen found higher proportions for some pathogens than studies seeking multiple pathogens (e.g. 39% rotavirus in 180 single-pathogen studies vs. 20% in 24 studies with 5–13 pathogens, p<0·0001). The percentage of episodes for which no pathogen could be identified was estimated to be 34%; the total of all age-adjusted percentages for pathogens and no-pathogen cases was 138%. Adjusting all proportions, including unknowns, to add to 100%, we estimated that rotavirus caused 197 000 [Uncertainty range (UR) 110 000–295 000], enteropathogenic E. coli 79 000 (UR 31 000–146 000), calicivirus 71 000 (UR 39 000–113 000), and enterotoxigenic E. coli 42 000 (UR 20 000–76 000) deaths. Rotavirus, calicivirus, enteropathogenic and enterotoxigenic E. coli cause more than half of all diarrheal deaths in children <5 years in the world.",2013 Sep 4,"['Lanata, Claudio F.', 'Fischer-Walker, Christa L.', 'Olascoaga, Ana C.', 'Torres, Carla X.', 'Aryee, Martin J.', 'Black, Robert E.', None]",PLoS One,,,True
6ad08282a281d311d1a9e87b8085a6f0c968ad50,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,True
2734a77d07ccffecc6409adaf6ccaba349155d7a,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
7f24652f604c181ad124bbd90019abcf45637ad5,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
6277fc8f2d8452c4130e5ae1f27b1678ba075f53,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
007e45183f45c14370636a1eaa6c5531dbcda45f,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
c5970d7ff79c420af4349f7c1fd7a3032de32b70,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
70fc6334817c8db13b936a2b96a072a7355ccbce,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
89bb0f2d1c9c091ce0d5b246976fb0f97d4fb2bd,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
31a5e7e1ec03528f7ef6755f6619f4509b3df2cc,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
31ad311010df14ce34534e925cec26f499109285,PMC,The Viruses of Wild Pigeon Droppings,http://dx.doi.org/10.1371/journal.pone.0072787,PMC3762862,24023772,CC BY,"Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.",2013 Sep 4,"['Phan, Tung Gia', 'Vo, Nguyen Phung', 'Boros, Ákos', 'Pankovics, Péter', 'Reuter, Gábor', 'Li, Olive T. W.', 'Wang, Chunling', 'Deng, Xutao', 'Poon, Leo L. M.', 'Delwart, Eric']",PLoS One,,,False
aef400eac72623d01820a1b2ca11e49a81917416,PMC,Human Health Risk Assessment (HHRA) for Environmental Development and Transfer of Antibiotic Resistance,http://dx.doi.org/10.1289/ehp.1206316,PMC3764079,23838256,CC0,"Background: Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks. Objective: We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens. Methods: The authors participated in a workshop held 4–8 March 2012 in Québec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development “hot spots,” exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options. Discussion: Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental “hot spot” compartments; and c) modifying traditional dose–response approaches to address doses of ARB for various health outcomes and pathways. Conclusions: We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers. Citation: Ashbolt NJ, Amézquita A, Backhaus T, Borriello P, Brandt KK, Collignon P, Coors A, Finley R, Gaze WH, Heberer T, Lawrence JR, Larsson DG, McEwen SA, Ryan JJ, Schönfeld J, Silley P, Snape JR, Van den Eede C, Topp E. 2013. Human health risk assessment (HHRA) for environmental development and transfer of antibiotic resistance. Environ Health Perspect 121:993–1001; http://dx.doi.org/10.1289/ehp.1206316",2013 Sep 9,"['Ashbolt, Nicholas J.', 'Amézquita, Alejandro', 'Backhaus, Thomas', 'Borriello, Peter', 'Brandt, Kristian K.', 'Collignon, Peter', 'Coors, Anja', 'Finley, Rita', 'Gaze, William H.', 'Heberer, Thomas', 'Lawrence, John R.', 'Larsson, D.G. Joakim', 'McEwen, Scott A.', 'Ryan, James J.', 'Schönfeld, Jens', 'Silley, Peter', 'Snape, Jason R.', 'Van den Eede, Christel', 'Topp, Edward']",Environ Health Perspect,,,True
1842bb195a368132b3f4b433e1b1a71590fdc31e,PMC,In Vitro Infection of Pupae with Israeli Acute Paralysis Virus Suggests Disturbance of Transcriptional Homeostasis in Honey Bees (Apis mellifera),http://dx.doi.org/10.1371/journal.pone.0073429,PMC3764161,24039938,CC0,"The ongoing decline of honey bee health worldwide is a serious economic and ecological concern. One major contributor to the decline are pathogens, including several honey bee viruses. However, information is limited on the biology of bee viruses and molecular interactions with their hosts. An experimental protocol to test these systems was developed, using injections of Israeli Acute Paralysis Virus (IAPV) into honey bee pupae reared ex-situ under laboratory conditions. The infected pupae developed pronounced but variable patterns of disease. Symptoms varied from complete cessation of development with no visual evidence of disease to rapid darkening of a part or the entire body. Considerable differences in IAPV titer dynamics were observed, suggesting significant variation in resistance to IAPV among and possibly within honey bee colonies. Thus, selective breeding for virus resistance should be possible. Gene expression analyses of three separate experiments suggest IAPV disruption of transcriptional homeostasis of several fundamental cellular functions, including an up-regulation of the ribosomal biogenesis pathway. These results provide first insights into the mechanisms of IAPV pathogenicity. They mirror a transcriptional survey of honey bees afflicted with Colony Collapse Disorder and thus support the hypothesis that viruses play a critical role in declining honey bee health.",2013 Sep 5,"['Boncristiani, Humberto F.', 'Evans, Jay D.', 'Chen, Yanping', 'Pettis, Jeff', 'Murphy, Charles', 'Lopez, Dawn L.', 'Simone-Finstrom, Michael', 'Strand, Micheline', 'Tarpy, David R.', 'Rueppell, Olav']",PLoS One,,,True
57e9dad391ccc19e24be64df52865485c942858a,PMC,In Vitro Infection of Pupae with Israeli Acute Paralysis Virus Suggests Disturbance of Transcriptional Homeostasis in Honey Bees (Apis mellifera),http://dx.doi.org/10.1371/journal.pone.0073429,PMC3764161,24039938,CC0,"The ongoing decline of honey bee health worldwide is a serious economic and ecological concern. One major contributor to the decline are pathogens, including several honey bee viruses. However, information is limited on the biology of bee viruses and molecular interactions with their hosts. An experimental protocol to test these systems was developed, using injections of Israeli Acute Paralysis Virus (IAPV) into honey bee pupae reared ex-situ under laboratory conditions. The infected pupae developed pronounced but variable patterns of disease. Symptoms varied from complete cessation of development with no visual evidence of disease to rapid darkening of a part or the entire body. Considerable differences in IAPV titer dynamics were observed, suggesting significant variation in resistance to IAPV among and possibly within honey bee colonies. Thus, selective breeding for virus resistance should be possible. Gene expression analyses of three separate experiments suggest IAPV disruption of transcriptional homeostasis of several fundamental cellular functions, including an up-regulation of the ribosomal biogenesis pathway. These results provide first insights into the mechanisms of IAPV pathogenicity. They mirror a transcriptional survey of honey bees afflicted with Colony Collapse Disorder and thus support the hypothesis that viruses play a critical role in declining honey bee health.",2013 Sep 5,"['Boncristiani, Humberto F.', 'Evans, Jay D.', 'Chen, Yanping', 'Pettis, Jeff', 'Murphy, Charles', 'Lopez, Dawn L.', 'Simone-Finstrom, Michael', 'Strand, Micheline', 'Tarpy, David R.', 'Rueppell, Olav']",PLoS One,,,False
2fb74042460bf37f74e93a6ee3d7997e82a43bdb,PMC,In Vitro Infection of Pupae with Israeli Acute Paralysis Virus Suggests Disturbance of Transcriptional Homeostasis in Honey Bees (Apis mellifera),http://dx.doi.org/10.1371/journal.pone.0073429,PMC3764161,24039938,CC0,"The ongoing decline of honey bee health worldwide is a serious economic and ecological concern. One major contributor to the decline are pathogens, including several honey bee viruses. However, information is limited on the biology of bee viruses and molecular interactions with their hosts. An experimental protocol to test these systems was developed, using injections of Israeli Acute Paralysis Virus (IAPV) into honey bee pupae reared ex-situ under laboratory conditions. The infected pupae developed pronounced but variable patterns of disease. Symptoms varied from complete cessation of development with no visual evidence of disease to rapid darkening of a part or the entire body. Considerable differences in IAPV titer dynamics were observed, suggesting significant variation in resistance to IAPV among and possibly within honey bee colonies. Thus, selective breeding for virus resistance should be possible. Gene expression analyses of three separate experiments suggest IAPV disruption of transcriptional homeostasis of several fundamental cellular functions, including an up-regulation of the ribosomal biogenesis pathway. These results provide first insights into the mechanisms of IAPV pathogenicity. They mirror a transcriptional survey of honey bees afflicted with Colony Collapse Disorder and thus support the hypothesis that viruses play a critical role in declining honey bee health.",2013 Sep 5,"['Boncristiani, Humberto F.', 'Evans, Jay D.', 'Chen, Yanping', 'Pettis, Jeff', 'Murphy, Charles', 'Lopez, Dawn L.', 'Simone-Finstrom, Michael', 'Strand, Micheline', 'Tarpy, David R.', 'Rueppell, Olav']",PLoS One,,,False
3bcd3d1d3d50b169ecc0397bf956a8c04c76c2bc,PMC,In Vitro Infection of Pupae with Israeli Acute Paralysis Virus Suggests Disturbance of Transcriptional Homeostasis in Honey Bees (Apis mellifera),http://dx.doi.org/10.1371/journal.pone.0073429,PMC3764161,24039938,CC0,"The ongoing decline of honey bee health worldwide is a serious economic and ecological concern. One major contributor to the decline are pathogens, including several honey bee viruses. However, information is limited on the biology of bee viruses and molecular interactions with their hosts. An experimental protocol to test these systems was developed, using injections of Israeli Acute Paralysis Virus (IAPV) into honey bee pupae reared ex-situ under laboratory conditions. The infected pupae developed pronounced but variable patterns of disease. Symptoms varied from complete cessation of development with no visual evidence of disease to rapid darkening of a part or the entire body. Considerable differences in IAPV titer dynamics were observed, suggesting significant variation in resistance to IAPV among and possibly within honey bee colonies. Thus, selective breeding for virus resistance should be possible. Gene expression analyses of three separate experiments suggest IAPV disruption of transcriptional homeostasis of several fundamental cellular functions, including an up-regulation of the ribosomal biogenesis pathway. These results provide first insights into the mechanisms of IAPV pathogenicity. They mirror a transcriptional survey of honey bees afflicted with Colony Collapse Disorder and thus support the hypothesis that viruses play a critical role in declining honey bee health.",2013 Sep 5,"['Boncristiani, Humberto F.', 'Evans, Jay D.', 'Chen, Yanping', 'Pettis, Jeff', 'Murphy, Charles', 'Lopez, Dawn L.', 'Simone-Finstrom, Michael', 'Strand, Micheline', 'Tarpy, David R.', 'Rueppell, Olav']",PLoS One,,,False
2f132252da880c9c19d5548ef6ab4ac752a90244,PMC,Emergence of the Middle East Respiratory Syndrome Coronavirus,http://dx.doi.org/10.1371/journal.ppat.1003595,PMC3764217,24039577,CC BY,,2013 Sep 5,"['Coleman, Christopher M.', 'Frieman, Matthew B.']",PLoS Pathog,,,True
b8e9fcc34571f9c29e04f9feb34197250556cb9a,PMC,"Mechanisms of protective immune responses induced by the Plasmodium falciparum circumsporozoite protein-based, self-assembling protein nanoparticle vaccine",http://dx.doi.org/10.1186/1475-2875-12-136,PMC3765086,23607541,CC BY,"BACKGROUND: A lack of defined correlates of immunity for malaria, combined with the inability to induce long-lived sterile immune responses in a human host, demonstrate a need for improved understanding of potentially protective immune mechanisms for enhanced vaccine efficacy. Protective sterile immunity (>90%) against the Plasmodium falciparum circumsporozoite protein (CSP) has been achieved using a transgenically modified Plasmodium berghei sporozoite (Tg-Pb/PfCSP) and a self-assembling protein nanoparticle (SAPN) vaccine presenting CSP epitopes (PfCSP-SAPN). Here, several possible mechanisms involved in the independently protective humoral and cellular responses induced following SAPN immunization are described. METHODS: Inbred mice were vaccinated with PfCSP-SAPN in PBS. Serum antibodies were harvested and effects on P. falciparum sporozoites mobility and integrity were examined using phase contrast microscopy. The functionality of SAPN-induced antibodies on inhibition of sporozoite invasion and growth within primary human hepatocytes was also examined. The internal processing of SAPN by bone marrow-derived dendritic cells (BMDDC), using organelle-specific, fluorescent-tagged antibody or gold-encapsulated SAPN, was observed using confocal or electron microscopy, respectively. RESULTS: The results of this work demonstrate that PfCSP-SAPN induces epitope-specific antibody titers, predominantly of the Th2 isotype IgG1, and that serum antibodies from PfCSP-SAPN-immunized mice appear to target P. falciparum sporozoites via the classical pathway of complement. This results in sporozoite death as indicated by cessation of motility and the circumsporozoite precipitation reaction. Moreover, PfCSP-SAPN-induced antibodies are able to inhibit wild-type P. falciparum sporozoite invasion and growth within cultured primary human hepatocytes. In addition, the observation that PfCSP-SAPN are processed (and presented) to the immune system by dendritic cells in a slow and continuous fashion via transporter associated with antigen processing (TAP) recruitment to the early endosome (EE), and have partially delayed processing through the endoplasmic reticulum, has the potential to induce the long-lived, effector memory CD8(+) T-cells as described previously. CONCLUSION: This paper describes the examination of humoral and cellular immune mechanisms induced by PfCSP-SAPN vaccination which result in sterile host protection against a transgenic P. berghei malaria sporozoite expressing the P. falciparum CSP, and which significantly inhibits native P. falciparum sporozoites from invading and developing within cultured human hepatocytes. These results may indicate the type and mode of action of protective antibodies needed to control P. falciparum sporozoites from infecting humans as well as a potential mechanism of induction of protective long-lived effector memory CD8(+) T-cells.",2013 Apr 22,"['McCoy, Margaret E', 'Golden, Hannah E', 'Doll, Tais APF', 'Yang, Yongkun', 'Kaba, Stephen A', 'Burkhard, Peter', 'Lanar, David E']",Malar J,,,True
7f9e15b30bfa7b75a43c5d9febf1b6f71240f80b,PMC,The TARGET cohort study protocol: a prospective primary care cohort study to derive and validate a clinical prediction rule to improve the targeting of antibiotics in children with respiratory tract illnesses,http://dx.doi.org/10.1186/1472-6963-13-322,PMC3765099,23958109,CC BY,"BACKGROUND: Children with respiratory tract infections are the single most frequent patient group to make use of primary care health care resources. The use of antibiotics remains highly prevalent in young children, but can lead to antimicrobial resistance as well as reinforcing the idea that parents should re-consult for similar symptoms. One of the main drivers of indiscriminate antimicrobial use is the lack of evidence for, and therefore uncertainty regarding, which children are at risk of poor outcome. This paper describes the protocol for the TARGET cohort study, which aims to derive and validate a clinical prediction rule to identify children presenting to primary care with respiratory tract infections who are at risk of hospitalisation. METHODS/DESIGN: The TARGET cohort study is a large, multicentre prospective observational study aiming to recruit 8,300 children aged ≥3 months and <16 years presenting to primary care with a cough and respiratory tract infection symptoms from 4 study centres (Bristol, London, Oxford and Southampton). Following informed consent, symptoms, signs and demographics will be measured. In around a quarter of children from the Bristol centre, a single sweep, dual bacterial-viral throat swab will be taken and parents asked to complete a symptom diary until the child is completely well or for 28 days, whichever is sooner. A review of medical notes including clinical history, re-consultation and hospitalisations will be undertaken. Multivariable logistic regression will be used to identify the independent clinical predictors of hospitalisation as well as the prognostic significance of upper respiratory tract microbes. The clinical prediction rule will be internally validated using various methods including bootstrapping. DISCUSSION: The clinical prediction rule for hospitalisation has the potential to help identify a small group of children for hospitalisation and a much larger group where hospitalisation is very unlikely and antibiotic prescribing would be less warranted. This study will also be the largest natural history study to date of children presenting to primary care with acute cough and respiratory tract infections, and will provide important information on symptom duration, re-consultations and the microbiology of the upper respiratory tract.",2013 Aug 17,"['Redmond, Niamh M', 'Davies, Rachel', 'Christensen, Hannah', 'Blair, Peter S', 'Lovering, Andrew M', 'Leeming, John P', 'Muir, Peter', 'Vipond, Barry', 'Thornton, Hannah', 'Fletcher, Margaret', 'Delaney, Brendan', 'Little, Paul', 'Thompson, Matthew', 'Peters, Tim J', 'Hay, Alastair D']",BMC Health Serv Res,,,True
8cc77f375b6cd2d7021976e3b6c43822f4243f3a,PMC,The TARGET cohort study protocol: a prospective primary care cohort study to derive and validate a clinical prediction rule to improve the targeting of antibiotics in children with respiratory tract illnesses,http://dx.doi.org/10.1186/1472-6963-13-322,PMC3765099,23958109,CC BY,"BACKGROUND: Children with respiratory tract infections are the single most frequent patient group to make use of primary care health care resources. The use of antibiotics remains highly prevalent in young children, but can lead to antimicrobial resistance as well as reinforcing the idea that parents should re-consult for similar symptoms. One of the main drivers of indiscriminate antimicrobial use is the lack of evidence for, and therefore uncertainty regarding, which children are at risk of poor outcome. This paper describes the protocol for the TARGET cohort study, which aims to derive and validate a clinical prediction rule to identify children presenting to primary care with respiratory tract infections who are at risk of hospitalisation. METHODS/DESIGN: The TARGET cohort study is a large, multicentre prospective observational study aiming to recruit 8,300 children aged ≥3 months and <16 years presenting to primary care with a cough and respiratory tract infection symptoms from 4 study centres (Bristol, London, Oxford and Southampton). Following informed consent, symptoms, signs and demographics will be measured. In around a quarter of children from the Bristol centre, a single sweep, dual bacterial-viral throat swab will be taken and parents asked to complete a symptom diary until the child is completely well or for 28 days, whichever is sooner. A review of medical notes including clinical history, re-consultation and hospitalisations will be undertaken. Multivariable logistic regression will be used to identify the independent clinical predictors of hospitalisation as well as the prognostic significance of upper respiratory tract microbes. The clinical prediction rule will be internally validated using various methods including bootstrapping. DISCUSSION: The clinical prediction rule for hospitalisation has the potential to help identify a small group of children for hospitalisation and a much larger group where hospitalisation is very unlikely and antibiotic prescribing would be less warranted. This study will also be the largest natural history study to date of children presenting to primary care with acute cough and respiratory tract infections, and will provide important information on symptom duration, re-consultations and the microbiology of the upper respiratory tract.",2013 Aug 17,"['Redmond, Niamh M', 'Davies, Rachel', 'Christensen, Hannah', 'Blair, Peter S', 'Lovering, Andrew M', 'Leeming, John P', 'Muir, Peter', 'Vipond, Barry', 'Thornton, Hannah', 'Fletcher, Margaret', 'Delaney, Brendan', 'Little, Paul', 'Thompson, Matthew', 'Peters, Tim J', 'Hay, Alastair D']",BMC Health Serv Res,,,False
3fb8269503a524e2257482ce479a05abd732ddfe,PMC,"Carcinoembryonic antigen (CEA)-related cell adhesion molecules are co-expressed in the human lung and their expression can be modulated in bronchial epithelial cells by non-typable Haemophilus influenzae, Moraxella catarrhalis, TLR3, and type I and II interferons",http://dx.doi.org/10.1186/1465-9921-14-85,PMC3765474,23941132,CC BY,"BACKGROUND: The carcinoembryonic antigen (CEA)-related cell adhesion molecules CEACAM1 (BGP, CD66a), CEACAM5 (CEA, CD66e) and CEACAM6 (NCA, CD66c) are expressed in human lung. They play a role in innate and adaptive immunity and are targets for various bacterial and viral adhesins. Two pathogens that colonize the normally sterile lower respiratory tract in patients with chronic obstructive pulmonary disease (COPD) are non-typable Haemophilus influenzae (NTHI) and Moraxella catarrhalis. Both pathogens bind to CEACAMs and elicit a variety of cellular reactions, including bacterial internalization, cell adhesion and apoptosis. METHODS: To analyze the (co-) expression of CEACAM1, CEACAM5 and CEACAM6 in different lung tissues with respect to COPD, smoking status and granulocyte infiltration, immunohistochemically stained paraffin sections of 19 donors were studied. To address short-term effects of cigarette smoke and acute inflammation, transcriptional regulation of CEACAM5, CEACAM6 and different CEACAM1 isoforms by cigarette smoke extract, interferons, Toll-like receptor agonists, and bacteria was tested in normal human bronchial epithelial (NHBE) cells by quantitative PCR. Corresponding CEACAM protein levels were determined by flow cytometry. RESULTS: Immunohistochemical analysis of lung sections showed the most frequent and intense staining for CEACAM1, CEACAM5 and CEACAM6 in bronchial and alveolar epithelium, but revealed no significant differences in connection with COPD, smoking status and granulocyte infiltration. In NHBE cells, mRNA expression of CEACAM1 isoforms CEACAM1-4L, CEACAM1-4S, CEACAM1-3L and CEACAM1-3S were up-regulated by interferons alpha, beta and gamma, as well as the TLR3 agonist polyinosinic:polycytidylic acid (poly I:C). Interferon-gamma also increased CEACAM5 expression. These results were confirmed on protein level by FACS analysis. Importantly, also NTHI and M. catarrhalis increased CEACAM1 mRNA levels. This effect was independent of the ability to bind to CEACAM1. The expression of CEACAM6 was not affected by any treatment or bacterial infection. CONCLUSIONS: While we did not find a direct correlation between CEACAM1 expression and COPD, the COPD-associated bacteria NTHi and M. catarrhalis were able to increase the expression of their own receptor on host cells. Further, the data suggest a role for CEACAM1 and CEACAM5 in the phenomenon of increased host susceptibility to bacterial infection upon viral challenge in the human respiratory tract.",2013 Aug 14,"['Klaile, Esther', 'Klassert, Tilman E', 'Scheffrahn, Inka', 'Müller, Mario M', 'Heinrich, Annina', 'Heyl, Kerstin A', 'Dienemann, Hendrik', 'Grünewald, Christiane', 'Bals, Robert', 'Singer, Bernhard B', 'Slevogt, Hortense']",Respir Res,,,True
39ab5e6b24f55e696076c53f96fc5704ff3ff0f0,PMC,Establishment of feline intestinal epithelial cell cultures for the propagation and study of feline enteric coronaviruses,http://dx.doi.org/10.1186/1297-9716-44-71,PMC3765525,23964891,CC BY,"Feline infectious peritonitis (FIP) is the most feared infectious cause of death in cats, induced by feline infectious peritonitis virus (FIPV). This coronavirus is a virulent mutant of the harmless, ubiquitous feline enteric coronavirus (FECV). To date, feline coronavirus (FCoV) research has been hampered by the lack of susceptible cell lines for the propagation of serotype I FCoVs. In this study, long-term feline intestinal epithelial cell cultures were established from primary ileocytes and colonocytes by simian virus 40 (SV40) T-antigen- and human Telomerase Reverse Transcriptase (hTERT)-induced immortalization. Subsequently, these cultures were evaluated for their usability in FCoV research. Firstly, the replication capacity of the serotype II strains WSU 79–1683 and WSU 79–1146 was studied in the continuous cultures as was done for the primary cultures. In accordance with the results obtained in primary cultures, FCoV WSU 79–1683 still replicated significantly more efficient compared to FCoV WSU 79–1146 in both continuous cultures. In addition, the cultures were inoculated with faecal suspensions from healthy cats and with faecal or tissue suspensions from FIP cats. The cultures were susceptible to infection with different serotype I enteric strains and two of these strains were further propagated. No infection was seen in cultures inoculated with FIPV tissue homogenates. In conclusion, a new reliable model for FCoV investigation and growth of enteric field strains was established. In contrast to FIPV strains, FECVs showed a clear tropism for intestinal epithelial cells, giving an explanation for the observation that FECV is the main pathotype circulating among cats.",2013 Aug 21,"['Desmarets, Lowiese MB', 'Theuns, Sebastiaan', 'Olyslaegers, Dominique AJ', 'Dedeurwaerder, Annelike', 'Vermeulen, Ben L', 'Roukaerts, Inge DM', 'Nauwynck, Hans J']",Vet Res,,,True
14c6dff031b3bcf8a7ea8486965b1dd888cf46a4,PMC,A safe and convenient pseudovirus-based inhibition assay to detect neutralizing antibodies and screen for viral entry inhibitors against the novel human coronavirus MERS-CoV,http://dx.doi.org/10.1186/1743-422X-10-266,PMC3765664,23978242,CC BY,"BACKGROUND: Evidence points to the emergence of a novel human coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), which causes a severe acute respiratory syndrome (SARS)-like disease. In response, the development of effective vaccines and therapeutics remains a clinical priority. To accomplish this, it is necessary to evaluate neutralizing antibodies and screen for MERS-CoV entry inhibitors. METHODS: In this study, we produced a pseudovirus bearing the full-length spike (S) protein of MERS-CoV in the Env-defective, luciferase-expressing HIV-1 backbone. We then established a pseudovirus-based inhibition assay to detect neutralizing antibodies and anti-MERS-CoV entry inhibitors. RESULTS: Our results demonstrated that the generated MERS-CoV pseudovirus allows for single-cycle infection of a variety of cells expressing dipeptidyl peptidase-4 (DPP4), the confirmed receptor for MERS-CoV. Consistent with the results from a live MERS-CoV-based inhibition assay, the antisera of mice vaccinated with a recombinant protein containing receptor-binding domain (RBD, residues 377–662) of MERS-CoV S fused with Fc of human IgG exhibited neutralizing antibody response against infection of MERS-CoV pseudovirus. Furthermore, one small molecule HIV entry inhibitor targeting gp41 (ADS-J1) and the 3-hydroxyphthalic anhydride-modified human serum albumin (HP-HSA) could significantly inhibit MERS-CoV pseudovirus infection. CONCLUSION: Taken together, the established MERS-CoV inhibition assay is a safe and convenient pseudovirus-based alternative to BSL-3 live-virus restrictions and can be used to rapidly screen MERS-CoV entry inhibitors, as well as evaluate vaccine-induced neutralizing antibodies against the highly pathogenic MERS-CoV.",2013 Aug 26,"['Zhao, Guangyu', 'Du, Lanying', 'Ma, Cuiqing', 'Li, Ye', 'Li, Lin', 'Poon, Vincent KM', 'Wang, Lili', 'Yu, Fei', 'Zheng, Bo-Jian', 'Jiang, Shibo', 'Zhou, Yusen']",Virol J,,,True
cee73a9e8367f60e1149b8db0b8a00a780c84d9d,PMC,Chikungunya virus capsid protein contains nuclear import and export signals,http://dx.doi.org/10.1186/1743-422X-10-269,PMC3765696,23984714,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is an alphavirus of the Togaviridae family. After autoproteolytic cleavage, the CHIKV capsid protein (CP) is involved in RNA binding and assembly of the viral particle. The monomeric CP is approximately 30 kDa in size and is small enough for passive transport through nuclear pores. Some alphaviruses are found to harbor nuclear localization signals (NLS) and transport of these proteins between cellular compartments was shown to be energy dependent. The active nuclear import of cytoplasmic proteins is mediated by karyopherins and their export by exportins. As nuclear and cytoplasmic trafficking may play a role in the life cycle of CHIKV, we have sought to identify nuclear localization and nuclear export signals in CHIKV CP in a virus-free system. METHODS: EGFP-fusion proteins of CHIKV CP and mutants thereof were created and used to monitor their intracellular localization. Binding of cellular proteins was confirmed in pull-down assays with purified CP using co-immuoprecipitation. Nuclear localization was demonstrated in a virus-free system using fluorescence microscopy. RESULTS: Here we show that CHIKV CP is a nuclear-cytoplasmic shuttling protein with an active NLS that binds to karyopherin α (Karα) for its nuclear translocation. We also found that the Karα4 C-terminal NLS binding site is sufficient for this interaction. We further demonstrate that CHIKV CP interacts directly with the export receptor CRM1 to transport this viral protein out of the nucleus via a nuclear export signal (NES). The CHIKV CP NES was mapped between amino acids 143 and 155 of CP. Deduced from in silico analyses we found that the NES has a mode of binding similar to the snurportin-1 CRM1 complex. CONCLUSIONS: We were able to show that in a virus-free system that the CHIKV capsid protein contains both, a NLS and a NES, and that it is actively transported between the cytoplasma and the nucleus. We conclude that CHIKV CP has the ability to shuttle via interaction with karyopherins for its nuclear import and, vice versa, by CRM1-dependent nuclear export.",2013 Aug 28,"['Thomas, Saijo', 'Rai, Jagdish', 'John, Lijo', 'Schaefer, Stephan', 'Pützer, Brigitte M', 'Herchenröder, Ottmar']",Virol J,,,True
cad994637f061356cd5ea11a7570b2f5ad38ed47,PMC,Estimating Potential Infection Transmission Routes in Hospital Wards Using Wearable Proximity Sensors,http://dx.doi.org/10.1371/journal.pone.0073970,PMC3770639,24040129,CC BY,"BACKGROUND: Contacts between patients, patients and health care workers (HCWs) and among HCWs represent one of the important routes of transmission of hospital-acquired infections (HAI). A detailed description and quantification of contacts in hospitals provides key information for HAIs epidemiology and for the design and validation of control measures. METHODS AND FINDINGS: We used wearable sensors to detect close-range interactions (“contacts”) between individuals in the geriatric unit of a university hospital. Contact events were measured with a spatial resolution of about 1.5 meters and a temporal resolution of 20 seconds. The study included 46 HCWs and 29 patients and lasted for 4 days and 4 nights. 14,037 contacts were recorded overall, 94.1% of which during daytime. The number and duration of contacts varied between mornings, afternoons and nights, and contact matrices describing the mixing patterns between HCW and patients were built for each time period. Contact patterns were qualitatively similar from one day to the next. 38% of the contacts occurred between pairs of HCWs and 6 HCWs accounted for 42% of all the contacts including at least one patient, suggesting a population of individuals who could potentially act as super-spreaders. CONCLUSIONS: Wearable sensors represent a novel tool for the measurement of contact patterns in hospitals. The collected data can provide information on important aspects that impact the spreading patterns of infectious diseases, such as the strong heterogeneity of contact numbers and durations across individuals, the variability in the number of contacts during a day, and the fraction of repeated contacts across days. This variability is however associated with a marked statistical stability of contact and mixing patterns across days. Our results highlight the need for such measurement efforts in order to correctly inform mathematical models of HAIs and use them to inform the design and evaluation of prevention strategies.",2013 Sep 11,"['Vanhems, Philippe', 'Barrat, Alain', 'Cattuto, Ciro', 'Pinton, Jean-François', 'Khanafer, Nagham', 'Régis, Corinne', 'Kim, Byeul-a', 'Comte, Brigitte', 'Voirin, Nicolas']",PLoS One,,,True
794b9541d676d262ebca65c8b3f1d7ca64d4441f,PMC,Molecular epidemiology of respiratory viruses in virus-induced asthma,http://dx.doi.org/10.3389/fmicb.2013.00278,PMC3771312,24062735,CC BY,"Acute respiratory illness (ARI) due to various viruses is not only the most common cause of upper respiratory infection in humans but is also a major cause of morbidity and mortality, leading to diseases such as bronchiolitis and pneumonia. Previous studies have shown that respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (HMPV), human parainfluenza virus (HPIV), and human enterovirus infections may be associated with virus-induced asthma. For example, it has been suggested that HRV infection is detected in the acute exacerbation of asthma and infection is prolonged. Thus it is believed that the main etiological cause of asthma is ARI viruses. Furthermore, the number of asthma patients in most industrial countries has greatly increased, resulting in a morbidity rate of around 10-15% of the population. However, the relationships between viral infections, host immune response, and host factors in the pathophysiology of asthma remain unclear. To gain a better understanding of the epidemiology of virus-induced asthma, it is important to assess both the characteristics of the viruses and the host defense mechanisms. Molecular epidemiology enables us to understand the pathogenesis of microorganisms by identifying specific pathways, molecules, and genes that influence the risk of developing a disease. However, the epidemiology of various respiratory viruses associated with virus-induced asthma is not fully understood. Therefore, in this article, we review molecular epidemiological studies of RSV, HRV, HPIV, and HMPV infection associated with virus-induced asthma.",2013 Sep 12,"['Tsukagoshi, Hiroyuki', 'Ishioka, Taisei', 'Noda, Masahiro', 'Kozawa, Kunihisa', 'Kimura, Hirokazu']",Front Microbiol,,,True
39d94b291715335c79664305706e67a752304121,PMC,"Outcome Risk Factors during Respiratory Infections in a Paediatric Ward in Antananarivo, Madagascar 2010–2012",http://dx.doi.org/10.1371/journal.pone.0072839,PMC3771918,24069161,CC BY,"BACKGROUND: Acute respiratory infections are a leading cause of infectious disease-related morbidity, hospitalisation and mortality among children worldwide, and particularly in developing countries. In these low-income countries, most patients with acute respiratory infection (ARI), whether it is mild or severe, are still treated empirically. The aim of the study was to evaluate the risk factors associated with the evolution and outcome of respiratory illnesses in patients aged under 5 years old. MATERIALS AND METHODS: We conducted a prospective study in a paediatric ward in Antananarivo from November 2010 to July 2012 including patients under 5 years old suffering from respiratory infections. We collected demographic, socio-economic, clinical and epidemiological data, and samples for laboratory analysis. Deaths, rapid progression to respiratory distress during hospitalisation, and hospitalisation for more than 10 days were considered as severe outcomes. We used multivariate analysis to study the effects of co-infections. RESULTS: From November 2010 to July 2012, a total of 290 patients were enrolled. Co-infection was found in 192 patients (70%). Co-infections were more frequent in children under 36 months, with a significant difference for the 19–24 month-old group (OR: 8.0). Sixty-nine percent (230/290) of the patients recovered fully and without any severe outcome during hospitalisation; the outcome was scored as severe for 60 children and nine patients (3%) died. Risk factors significantly associated with worsening evolution during hospitalisation (severe outcome) were admission at age under 6 months (OR = 5.3), comorbidity (OR = 4.6) and low household income (OR = 4.1). CONCLUSION: Co-mordidity, low-income and age under 6 months increase the risk of severe outcome for children infected by numerous respiratory pathogens. These results highlight the need for implementation of targeted public health policy to reduce the contribution of respiratory diseases to childhood morbidity and mortality in low income countries.",2013 Sep 12,"['Rajatonirina, Soatiana', 'Razanajatovo, Norosoa Harline', 'Ratsima, Elisoa Hariniana', 'Orelle, Arnaud', 'Ratovoson, Rila', 'Andrianirina, Zo Zafitsara', 'Andriatahina, Todisoa', 'Ramparany, Lovasoa', 'Herindrainy, Perlinot', 'Randrianirina, Frédérique', 'Heraud, Jean-Michel', 'Richard, Vincent']",PLoS One,,,True
04cf308cfa2f72131ecbb07bacb894bab15aa66e,PMC,"A Fusion-Inhibiting Peptide against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses",http://dx.doi.org/10.1371/journal.pntd.0002430,PMC3772029,24069485,CC0,"For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III) based on the protein sequence and structure. For Rift Valley fever virus (RVFV), the glycoprotein Gc (Class II fusion protein) mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus), Class II (Andes virus), or Class III (vesicular stomatitis virus) fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors.",2013 Sep 12,"['Koehler, Jeffrey W.', 'Smith, Jeffrey M.', 'Ripoll, Daniel R.', 'Spik, Kristin W.', 'Taylor, Shannon L.', 'Badger, Catherine V.', 'Grant, Rebecca J.', 'Ogg, Monica M.', 'Wallqvist, Anders', 'Guttieri, Mary C.', 'Garry, Robert F.', 'Schmaljohn, Connie S.']",PLoS Negl Trop Dis,,,True
0efede5fe4185af68b00ac20b99399af133e80bb,PMC,"Transcriptome Analysis of Human Peripheral Blood Mononuclear Cells Exposed to Lassa Virus and to the Attenuated Mopeia/Lassa Reassortant 29 (ML29), a Vaccine Candidate",http://dx.doi.org/10.1371/journal.pntd.0002406,PMC3772037,24069471,CC0,"Lassa virus (LASV) is the causative agent of Lassa Fever and is responsible for several hundred thousand infections and thousands of deaths annually in West Africa. LASV and the non-pathogenic Mopeia virus (MOPV) are both rodent-borne African arenaviruses. A live attenuated reassortant of MOPV and LASV, designated ML29, protects rodents and primates from LASV challenge and appears to be more attenuated than MOPV. To gain better insight into LASV-induced pathology and mechanism of attenuation we performed gene expression profiling in human peripheral blood mononuclear cells (PBMC) exposed to LASV and the vaccine candidate ML29. PBMC from healthy human subjects were exposed to either LASV or ML29. Although most PBMC are non-permissive for virus replication, they remain susceptible to signal transduction by virus particles. Total RNA was extracted and global gene expression was evaluated during the first 24 hours using high-density microarrays. Results were validated using RT-PCR, flow cytometry and ELISA. LASV and ML29 elicited differential expression of interferon-stimulated genes (ISG), as well as genes involved in apoptosis, NF-kB signaling and the coagulation pathways. These genes could eventually serve as biomarkers to predict disease outcomes. The remarkable differential expression of thrombomodulin, a key regulator of inflammation and coagulation, suggests its involvement with vascular abnormalities and mortality in Lassa fever disease.",2013 Sep 12,"['Zapata, Juan Carlos', 'Carrion, Ricardo', 'Patterson, Jean L.', 'Crasta, Oswald', 'Zhang, Yan', 'Mani, Sachin', 'Jett, Marti', 'Poonia, Bhawna', 'Djavani, Mahmoud', 'White, David M.', 'Lukashevich, Igor S.', 'Salvato, Maria S.']",PLoS Negl Trop Dis,,,True
6c9d5c49fd907d0380d25e4df6cac63b00bce66b,PMC,A Neutralizing Monoclonal Antibody Targeting the Acid-Sensitive Region in Chikungunya Virus E2 Protects from Disease,http://dx.doi.org/10.1371/journal.pntd.0002423,PMC3772074,24069479,CC BY,"The mosquito-borne alphavirus, chikungunya virus (CHIKV), has recently reemerged, producing the largest epidemic ever recorded for this virus, with up to 6.5 million cases of acute and chronic rheumatic disease. There are currently no licensed vaccines for CHIKV and current anti-inflammatory drug treatment is often inadequate. Here we describe the isolation and characterization of two human monoclonal antibodies, C9 and E8, from CHIKV infected and recovered individuals. C9 was determined to be a potent virus neutralizing antibody and a biosensor antibody binding study demonstrated it recognized residues on intact CHIKV VLPs. Shotgun mutagenesis alanine scanning of 98 percent of the residues in the E1 and E2 glycoproteins of CHIKV envelope showed that the epitope bound by C9 included amino-acid 162 in the acid-sensitive region (ASR) of the CHIKV E2 glycoprotein. The ASR is critical for the rearrangement of CHIKV E2 during fusion and viral entry into host cells, and we predict that C9 prevents these events from occurring. When used prophylactically in a CHIKV mouse model, C9 completely protected against CHIKV viremia and arthritis. We also observed that when administered therapeutically at 8 or 18 hours post-CHIKV challenge, C9 gave 100% protection in a pathogenic mouse model. Given that targeting this novel neutralizing epitope in E2 can potently protect both in vitro and in vivo, it is likely to be an important region both for future antibody and vaccine-based interventions against CHIKV.",2013 Sep 12,"['Selvarajah, Suganya', 'Sexton, Nicole R.', 'Kahle, Kristen M.', 'Fong, Rachel H.', 'Mattia, Kimberly-Anne', 'Gardner, Joy', 'Lu, Kai', 'Liss, Nathan M.', 'Salvador, Beatriz', 'Tucker, David F.', 'Barnes, Trevor', 'Mabila, Manu', 'Zhou, Xiangdong', 'Rossini, Giada', 'Rucker, Joseph B.', 'Sanders, David Avram', 'Suhrbier, Andreas', 'Sambri, Vittorio', 'Michault, Alain', 'Muench, Marcus O.', 'Doranz, Benjamin J.', 'Simmons, Graham']",PLoS Negl Trop Dis,,,True
d4ea57e72c426571255c1c45861db4c6b46b95d5,PMC,Pathogenic Mouse Hepatitis Virus or Poly(I:C) Induce IL-33 in Hepatocytes in Murine Models of Hepatitis,http://dx.doi.org/10.1371/journal.pone.0074278,PMC3772926,24058536,CC BY,"The IL-33/ST2 axis is known to be involved in liver pathologies. Although, the IL-33 levels increased in sera of viral hepatitis patients in human, the cellular sources of IL-33 in viral hepatitis remained obscure. Therefore, we aimed to investigate the expression of IL-33 in murine fulminant hepatitis induced by a Toll like receptor (TLR3) viral mimetic, poly(I:C) or by pathogenic mouse hepatitis virus (L2-MHV3). The administration of poly(I:C) plus D-galactosamine (D-GalN) in mice led to acute liver injury associated with the induction of IL-33 expression in liver sinusoidal endothelial cells (LSEC) and vascular endothelial cells (VEC), while the administration of poly(I:C) alone led to hepatocyte specific IL-33 expression in addition to vascular IL-33 expression. The hepatocyte-specific IL-33 expression was down-regulated in NK-depleted poly(I:C) treated mice suggesting a partial regulation of IL-33 by NK cells. The CD1d KO (NKT deficient) mice showed hepatoprotection against poly(I:C)-induced hepatitis in association with increased number of IL-33 expressing hepatocytes in CD1d KO mice than WT controls. These results suggest that hepatocyte-specific IL-33 expression in poly(I:C) induced liver injury was partially dependent of NK cells and with limited role of NKT cells. In parallel, the L2-MHV3 infection in mice induced fulminant hepatitis associated with up-regulated IL-33 expression as well as pro-inflammatory cytokine microenvironment in liver. The LSEC and VEC expressed inducible expression of IL-33 following L2-MHV3 infection but the hepatocyte-specific IL-33 expression was only evident between 24 to 32h of post infection. In conclusion, the alarmin cytokine IL-33 was over-expressed during fulminant hepatitis in mice with LSEC, VEC and hepatocytes as potential sources of IL-33.",2013 Sep 13,"['Arshad, Muhammad Imran', 'Patrat-Delon, Solène', 'Piquet-Pellorce, Claire', 'L’Helgoualc’h, Annie', 'Rauch, Michel', 'Genet, Valentine', 'Lucas-Clerc, Catherine', 'Bleau, Christian', 'Lamontagne, Lucie', 'Samson, Michel']",PLoS One,,,True
aef63beff452ee2eee54c7d60770dccf59890568,PMC,The Effectiveness and Mechanism of Toona sinensis Extract Inhibit Attachment of Pandemic Influenza A (H1N1) Virus,http://dx.doi.org/10.1155/2013/479718,PMC3773900,24073006,CC BY,"TSL-1 is a fraction of the aqueous extract from the tender leaf of Toona sinensis Roem, a nutritious vegetable. The pandemic influenza A (H1N1) virus is a recently described, rapidly contagious respiratory pathogen which can cause acute respiratory distress syndrome (ARDS) and poses a major public health threat. In this study, we found that TSL-1 inhibited viral yields on MDCK plaque formation by pandemic influenza A (H1N1) virus on infected A549 cells with high selectivity index. Meanwhile, TSL-1 also suppressed viral genome loads in infected A549 cells, quantified by qRT-PCR. This study further demonstrated that TSL-1 inhibited pandemic influenza A (H1N1) virus activity through preventing attachment of A549 cells but not penetration. TSL-1 inhibited viral attachment through significant downregulation of adhesion molecules and chemokines (VCAM-1, ICAM-1, E-selectin, IL-8, and fractalkine) compared to Amantadine. Our results suggest that TSL-1 may be used as an alternative treatment and prophylaxis against pandemic influenza A (H1N1) virus.",2013 Sep 2,"['You, Huey-Ling', 'Chen, Chung-Jen', 'Eng, Hock-Liew', 'Liao, Pei-Lin', 'Huang, Sheng-Teng']",Evid Based Complement Alternat Med,,,True
593d2241563c6bf2e57327ce40e7e83dacbd80fc,PMC,A Simple Methodology for Conversion of Mouse Monoclonal Antibody to Human-Mouse Chimeric Form,http://dx.doi.org/10.1155/2013/716961,PMC3775440,24078817,CC BY,"Passive immunotherapy has mainly been used as a therapy against cancer and inflammatory conditions. Recent studies have shown that monoclonal antibody-(mAb-) based passive immunotherapy is a promising approach to combat virus infection. Specific mouse mAbs can be routinely generated in large amounts with the use of hybridoma technology but these cannot be used for therapy in human beings due to their immunogenicity. Therefore, the development of chimeric and humanized mAbs is important for therapeutic purpose. This is facilitated by a variety of molecular techniques like recombinant DNA technology and the better understanding of the structure and function of antibody. The human-mouse chimeric forms allow detailed analysis of the mechanism of inhibition and the potential for therapeutic applications. Here, a step-by-step description of the conversion process will be described. The commercial availability of the reagents required in each step means that this experimentation can be easily set up in research laboratories.",2013 Sep 2,"['Dang, Vinh T.', 'Mandakhalikar, Kedar D.', 'Ng, Oi-Wing', 'Tan, Yee-Joo']",Clin Dev Immunol,,,True
062a18fe6bcaad19bd60d8b47d3287079a915545,PMC,Clinical Features and Factors Associated with Outcomes of Patients Infected with a Novel Influenza A (H7N9) Virus: A Preliminary Study,http://dx.doi.org/10.1371/journal.pone.0073362,PMC3775774,24069191,CC BY,"OBJECTIVE: The present study aimed to analyze clinical features and factors associated with treatment outcomes of H7N9 influenza A virus infection. METHODS: The clinical progress in 18 H7N9-infected patients was monitored and recorded. The clinical features of H7N9 infection were noted and factors associated with treatment outcomes were analyzed by univariate analyses. RESULTS: The average ages of patients in recovered and critical conditions were 67.0±10.83 years and 72.75±12.0 years, respectively. Renal insufficiency developed more frequently in critically ill patients (P = 0.023). The duration of traditional Chinese medicine (TCM) therapy was longer in recovered patients than in critically ill patients (P = 0.01). Laboratory tests showed that levels of C-reactive protein, serum creatinine, and myoglobin were significantly higher in critically ill patients than in recovered patients (P = 0.011, 0.04, and 0.016, respectively). Meanwhile, levels of all T cell subsets examined including total CD3(+), CD4(+), CD8(+), and CD45(+) T cells were lower in critically ill patients than in recovered patients (P = 0.033, 0.059, 0.015, and 0.039, respectively). Logistic regression analysis demonstrated that C-reactive protein level, myoglobin level and TCM therapy duration were likely associated with treatment outcomes of H7N9 infection (P = 0.032, 0.041 and 0.017, respectively). CONCLUSION: Elderly people may have increased risk for H7N9 virus infection. T cell-mediated responses play an important role in defense against the H7N9 virus. C-reactive protein level, myoglobin level and TCM duration may be associated with treatment outcomes of H7N9 infection.",2013 Sep 17,"['Chen, Xiaorong', 'Yang, Zongguo', 'Lu, Yunfei', 'Xu, Qingnian', 'Wang, Qiang', 'Chen, Liang']",PLoS One,,,True
bd7f96581b36339bff8aca7e50e1b91f333fc00e,PMC,The political economy of healthcare reform in China: negotiating public and private,http://dx.doi.org/10.1186/2193-1801-2-448,PMC3776089,24052932,CC BY,"China’s healthcare system is experiencing significant growth from expanded government-backed insurance, greater public-sector spending on hospitals, and the introduction of private insurance and for-profit clinics. An incremental reform process has sought to develop market incentives for medical innovation and liberalize physician compensation and hospital finance while continuing to keep basic care affordable to a large population that pays for many components of care out-of-pocket. Additional changes presently under consideration by policymakers are likely to further restructure insurance and the delivery of care and will alter competitive dynamics in major healthcare industries, notably pharmaceuticals, medical devices, and diagnostic testing. This article describes the institutional history of China’s healthcare system and identifies dilemmas emerging as the country negotiates divisions between public and private in healthcare. Building on this analysis, the article considers opportunities for public-private partnerships and greater systems integration to reconcile otherwise incommensurable approaches to rewarding innovation and improving access. The article concludes with observations on the public function of health insurance and its significance to further development of China’s healthcare system.",2013 Sep 10,"Daemmrich, Arthur",Springerplus,,,True
0d8784d230453109b9340461f2692f0f2d048927,PMC,Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells,http://dx.doi.org/10.1371/journal.pone.0075831,PMC3776769,24058703,CC BY,"Recently, one of the interferon-induced transmembrane (IFITM) family proteins, IFITM3, has become an important target for the activity against influenza A (H1N1) virus infection. In this protein, a post-translational modification by fatty acids covalently attached to cysteine, termed S-palmitoylation, plays a crucial role for the antiviral activity. IFITM3 possesses three cysteine residues for the S-palmitoylation in the first transmembrane (TM1) domain and in the cytoplasmic (CP) loop. Because these cysteines are well conserved in the mammalian IFITM family proteins, the S-palmitoylation on these cysteines is significant for their functions. IFITM5 is another IFITM family protein and interacts with the FK506-binding protein 11 (FKBP11) to form a higher-order complex in osteoblast cells, which induces the expression of immunologically relevant genes. In this study, we investigated the role played by S-palmitoylation of IFITM5 in its interaction with FKBP11 in the cells, because this interaction is a key process for the gene expression. Our investigations using an established reporter, 17-octadecynoic acid (17-ODYA), and an inhibitor for the S-palmitoylation, 2-bromopalmitic acid (2BP), revealed that IFITM5 was S-palmitoylated in addition to IFITM3. Specifically, we found that cysteine residues in the TM1 domain and in the CP loop were S-palmitoylated in IFITM5. Then, we revealed by immunoprecipitation and western blot analyses that the interaction of IFITM5 with FKBP11 was inhibited in the presence of 2BP. The mutant lacking the S-palmitoylation site in the TM1 domain lost the interaction with FKBP11. These results indicate that the S-palmitoylation on IFITM5 promotes the interaction with FKBP11. Finally, we investigated bone nodule formation in osteoblast cells in the presence of 2BP, because IFITM5 was originally identified as a bone formation factor. The experiment resulted in a morphological aberration of the bone nodule. This also indicated that the S-palmitoylation contributes to bone formation.",2013 Sep 18,"['Tsukamoto, Takashi', 'Li, Xianglan', 'Morita, Hiromi', 'Minowa, Takashi', 'Aizawa, Tomoyasu', 'Hanagata, Nobutaka', 'Demura, Makoto']",PLoS One,,,True
4bd41e4fe399ecfd7456792b11f51979999b4d1e,PMC,Hepatitis C Virus Replication and Golgi Function in Brefeldin A-Resistant Hepatoma-Derived Cells,http://dx.doi.org/10.1371/journal.pone.0074491,PMC3776844,24058576,CC BY,"Recent reports indicate that the replication of hepatitis C virus (HCV) depends on the GBF1-Arf1-COP-I pathway. We generated Huh-7-derived cell lines resistant to brefeldin A (BFA), which is an inhibitor of this pathway. The resistant cell lines could be sorted into two phenotypes regarding BFA-induced toxicity, inhibition of albumin secretion, and inhibition of HCV infection. Two cell lines were more than 100 times more resistant to BFA than the parental Huh-7 cells in these 3 assays. This resistant phenotype was correlated with the presence of a point mutation in the Sec7 domain of GBF1, which is known to impair the binding of BFA. Surprisingly, the morphology of the cis-Golgi of these cells remained sensitive to BFA at concentrations of the drug that allowed albumin secretion, indicating a dichotomy between the phenotypes of secretion and Golgi morphology. Cells of the second group were about 10 times more resistant than parental Huh-7 cells to the BFA-induced toxicity. The EC(50) for albumin secretion was only 1.5–1.8 fold higher in these cells than in Huh-7 cells. However their level of secretion in the presence of inhibitory doses of BFA was 5 to 15 times higher. Despite this partially effective secretory pathway in the presence of BFA, the HCV infection was almost as sensitive to BFA as in Huh-7 cells. This suggests that the function of GBF1 in HCV replication does not simply reflect its role of regulator of the secretory pathway of the host cell. Thus, our results confirm the involvement of GBF1 in HCV replication, and suggest that GBF1 might fulfill another function, in addition to the regulation of the secretory pathway, during HCV replication.",2013 Sep 18,"['Farhat, Rayan', 'Goueslain, Lucie', 'Wychowski, Czeslaw', 'Belouzard, Sandrine', 'Fénéant, Lucie', 'Jackson, Catherine L.', 'Dubuisson, Jean', 'Rouillé, Yves']",PLoS One,,,True
45dd7b43349a7cd110254e46282dd4968dcdffbe,PMC,Analysis of the Host Transcriptome from Demyelinating Spinal Cord of Murine Coronavirus-Infected Mice,http://dx.doi.org/10.1371/journal.pone.0075346,PMC3776850,24058676,CC BY,"Persistent infection of the mouse central nervous system (CNS) with mouse hepatitis virus (MHV) induces a demyelinating disease pathologically similar to multiple sclerosis and is therefore used as a model system. There is little information regarding the host factors that correlate with and contribute to MHV-induced demyelination. Here, we detail the genes and pathways associated with MHV-induced demyelinating disease in the spinal cord. High-throughput sequencing of the host transcriptome revealed that demyelination is accompanied by numerous transcriptional changes indicative of immune infiltration as well as changes in the cytokine milieu and lipid metabolism. We found evidence that a Th1-biased cytokine/chemokine response and eicosanoid-derived inflammation accompany persistent MHV infection and that antigen presentation is ongoing. Interestingly, increased expression of genes involved in lipid transport, processing, and catabolism, including some with known roles in neurodegenerative diseases, coincided with demyelination. Lastly, expression of several genes involved in osteoclast or bone-resident macrophage function, most notably TREM2 and DAP12, was upregulated in persistently infected mouse spinal cord. This study highlights the complexity of the host antiviral response, which accompany MHV-induced demyelination, and further supports previous findings that MHV-induced demyelination is immune-mediated. Interestingly, these data suggest a parallel between bone reabsorption by osteoclasts and myelin debris clearance by microglia in the bone and the CNS, respectively. To our knowledge, this is the first report of using an RNA-seq approach to study the host CNS response to persistent viral infection.",2013 Sep 18,"['Elliott, Ruth', 'Li, Fan', 'Dragomir, Isabelle', 'Chua, Ming Ming W.', 'Gregory, Brian D.', 'Weiss, Susan R.']",PLoS One,,,True
ede3bef01a48a154a93f1286b907cd5a53a086eb,PMC,Vesicular Transport of Progeny Parvovirus Particles through ER and Golgi Regulates Maturation and Cytolysis,http://dx.doi.org/10.1371/journal.ppat.1003605,PMC3777860,24068925,CC BY,"Progeny particles of non-enveloped lytic parvoviruses were previously shown to be actively transported to the cell periphery through vesicles in a gelsolin-dependent manner. This process involves rearrangement and destruction of actin filaments, while microtubules become protected throughout the infection. Here the focus is on the intracellular egress pathway, as well as its impact on the properties and release of progeny virions. By colocalization with cellular marker proteins and specific modulation of the pathways through over-expression of variant effector genes transduced by recombinant adeno-associated virus vectors, we show that progeny PV particles become engulfed into COPII-vesicles in the endoplasmic reticulum (ER) and are transported through the Golgi to the plasma membrane. Besides known factors like sar1, sec24, rab1, the ERM family proteins, radixin and moesin play (an) essential role(s) in the formation/loading and targeting of virus-containing COPII-vesicles. These proteins also contribute to the transport through ER and Golgi of the well described analogue of cellular proteins, the secreted Gaussia luciferase in absence of virus infection. It is therefore likely that radixin and moesin also serve for a more general function in cellular exocytosis. Finally, parvovirus egress via ER and Golgi appears to be necessary for virions to gain full infectivity through post-assembly modifications (e.g. phosphorylation). While not being absolutely required for cytolysis and progeny virus release, vesicular transport of parvoviruses through ER and Golgi significantly accelerates these processes pointing to a regulatory role of this transport pathway.",2013 Sep 19,"['Bär, Séverine', 'Rommelaere, Jean', 'Nüesch, Jürg P. F.']",PLoS Pathog,,,True
8f98c8621da6438169976931b2bc2cce12959a70,PMC,Rab-GDI Complex Dissociation Factor Expressed through Translational Frameshifting in Filamentous Ascomycetes,http://dx.doi.org/10.1371/journal.pone.0073772,PMC3777964,24069231,CC BY,"In the model fungus Podospora anserina, the PaYIP3 gene encoding the orthologue of the Saccharomyces cerevisiae YIP3 Rab-GDI complex dissociation factor expresses two polypeptides, one of which, the long form, is produced through a programmed translation frameshift. Inactivation of PaYIP3 results in slightly delayed growth associated with modification in repartition of fruiting body on the thallus, along with reduced ascospore production on wood. Long and short forms of PaYIP3 are expressed in the mycelium, while only the short form appears expressed in the maturing fruiting body (perithecium). The frameshift has been conserved over the evolution of the Pezizomycotina, lasting for over 400 million years, suggesting that it has an important role in the wild.",2013 Sep 19,"['Malagnac, Fabienne', 'Fabret, Céline', 'Prigent, Magali', 'Rousset, Jean-Pierre', 'Namy, Olivier', 'Silar, Philippe']",PLoS One,,,True
e54a9696e0da89388b8edef0dbe18a5f674a245b,PMC,"Virological Surveillance of Influenza Viruses during the 2008–09, 2009–10 and 2010–11 Seasons in Tunisia",http://dx.doi.org/10.1371/journal.pone.0074064,PMC3777972,24069267,CC BY,"BACKGROUND: The data contribute to a better understanding of the circulation of influenza viruses especially in North-Africa. OBJECTIVE: The objective of this surveillance was to detect severe influenza cases, identify their epidemiological and virological characteristics and assess their impact on the healthcare system. METHOD: We describe in this report the findings of laboratory-based surveillance of human cases of influenza virus and other respiratory viruses' infection during three seasons in Tunisia. RESULTS: The 2008–09 winter influenza season is underway in Tunisia, with co-circulation of influenza A/H3N2 (56.25%), influenza A(H1N1) (32.5%), and a few sporadic influenza B viruses (11.25%). In 2010–11 season the circulating strains are predominantly the 2009 pandemic influenza A(H1N1)pdm09 (70%) and influenza B viruses (22%). And sporadic viruses were sub-typed as A/H3N2 and unsubtyped influenza A, 5% and 3%, respectively. Unlike other countries, highest prevalence of influenza B virus Yamagata-like lineage has been reported in Tunisia (76%) localised into the clade B/Bangladesh/3333/2007. In the pandemic year, influenza A(H1N1)pdm09 predominated over other influenza viruses (95%). Amino acid changes D222G and D222E were detected in the HA gene of A(H1N1)pdm09 virus in two severe cases, one fatal case and one mild case out of 50 influenza A(H1N1)pdm09 viruses studied. The most frequently reported respiratory virus other than influenza in three seasons was RSV (45.29%). CONCLUSION: This article summarises the surveillance and epidemiology of influenza viruses and other respiratory viruses, showing how rapid improvements in influenza surveillance were feasible by connecting the existing structure in the health care system for patient records to electronic surveillance system for reporting ILI cases.",2013 Sep 19,"['El Moussi, Awatef', 'Pozo, Francisco', 'Ben Hadj Kacem, Mohamed Ali', 'Ledesma, Juan', 'Cuevas, Maria Teresa', 'Casas, Inmaculada', 'Slim, Amine']",PLoS One,,,True
f71d759c61dcef328233eb5cb93e7c5f101fa111,PMC,Acute phase response to Mycoplasma haemofelis and ‘Candidatus Mycoplasma haemominutum’ infection in FIV-infected and non-FIV-infected cats,http://dx.doi.org/10.1016/j.tvjl.2011.12.009,PMC3778745,22763129,CC BY,"The pathogenicity of Haemoplasma spp. in cats varies with ‘Candidatus Mycoplasma haemominutum’ (CMhm) causing subclinical infection while Mycoplasma haemofelis (Mhf) often induces haemolytic anaemia. The aims of this study were to characterise the acute phase response (APR) of the cat to experimental infection with Mhf or CMhm, and to determine whether chronic feline immunodeficiency virus (FIV) infection influences this response. The acute phase proteins serum amyloid A (SAA), haptoglobin (Hp) and α-1-acid glycoprotein (AGP) concentrations were measured pre-infection and every 7–14 days up to day 100 post-infection (pi) in cats infected with either Mhf or CMhm. Half of each group of cats (6/12) were chronically and subclinically infected with FIV. Marbofloxacin treatment was given on days 16–44 pi to half of the Mhf-infected cats, and on days 49–77 pi to half of the CMhm-infected cats. FIV-infected animals had significantly lower AGP concentrations, and significantly greater Hp concentrations than non-FIV-infected cats when infected with CMhm and Mhf, respectively. Both CMhm and Mhf infection were associated with significant increases in SAA concentrations, while AGP concentrations were only significantly increased by Mhf infection. Mhf-infected cats had significantly greater SAA concentrations than CMhm-infected animals. Both Mhf and CMhm infections were associated with an APR, with Mhf infection inducing a greater response. Chronic FIV infection appeared to modify the APR, which varied with the infecting Haemoplasma species.",2012 Aug,"['Korman, R.M.', 'Cerón, J.J.', 'Knowles, T.G.', 'Barker, E.N.', 'Eckersall, P.D.', 'Tasker, S.']",Vet J,,,False
f292a5fa02dc7ce9ea268920cc8657f4e34360f9,PMC,Different Mechanisms of Inflammation Induced in Virus and Autoimmune-Mediated Models of Multiple Sclerosis in C57BL6 Mice,http://dx.doi.org/10.1155/2013/589048,PMC3780522,24083230,CC BY,"Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system (CNS). Neurotropic demyelinating strain of MHV (MHV-A59 or its isogenic recombinant strain RSA59) induces MS-like disease in mice mediated by microglia, along with a small population of T cells. The mechanism of demyelination is at least in part due to microglia-mediated myelin stripping, with some direct axonal injury. Immunization with myelin oligodendrocyte glycoprotein (MOG) induces experimental autoimmune encephalomyelitis (EAE), a mainly CD4(+) T-cell-mediated disease, although CD8(+) T cells may play a significant role in demyelination. It is possible that both autoimmune and nonimmune mechanisms such as direct viral toxicity may induce MS. Our study directly compares CNS pathology in autoimmune and viral-induced MS models. Mice with viral-induced and EAE demyelinating diseases demonstrated similar patterns and distributions of demyelination that accumulated over the course of the disease. However, significant differences in acute inflammation were noted. Inflammation was restricted mainly to white matter at all times in EAE, whereas inflammation initially largely involved gray matter in acute MHV-induced disease and then is subsequently localized only in white matter in the chronic disease phase. The presence of dual mechanisms of demyelination may be responsible for the failure of immunosuppression to promote long-term remission in many MS patients.",2013 Aug 28,"['Kishore, Abhinoy', 'Kanaujia, Anurag', 'Nag, Soma', 'Rostami, A. M.', 'Kenyon, Lawrence C.', 'Shindler, Kenneth S.', 'Das Sarma, Jayasri']",Biomed Res Int,,,True
5b36690d168ab53e08482ce4b4b956d9ad3c1a10,PMC,Soluble Form of Canine Transferrin Receptor Inhibits Canine Parvovirus Infection In Vitro and In Vivo,http://dx.doi.org/10.1155/2013/172479,PMC3780538,24089666,CC BY,"Canine parvovirus (CPV) disease is an acute, highly infectious disease threatening the dog-raising industry. So far there are no effective therapeutic strategies to control this disease. Although the canine transferrin receptor (TfR) was identified as a receptor for CPV infection, whether extracellular domain of TfR (called soluble TfR (sTfR)) possesses anti-CPV activities remains elusive. Here, we used the recombinant sTfR prepared from HEK293T cells with codon-optimized gene structure to investigate its anti-CPV activity both in vitro and in vivo. Our results indicated that codon optimization could significantly improve sTfR expression in HEK293T cells. The prepared recombinant sTfR possessed a binding activity to both CPV and CPV VP2 capsid proteins and significantly inhibited CPV infection of cultured feline F81 cells and decreased the mortality of CPV-infected dogs, which indicates that the sTfR has the anti-CPV activity both in vitro and in vivo.",2013 Sep 8,"['Wen, Jiexia', 'Pan, Sumin', 'Liang, Shuang', 'Zhong, Zhenyu', 'He, Ying', 'Lin, Hongyu', 'Li, Wenyan', 'Wang, Liyue', 'Li, Xiujin', 'Zhong, Fei']",Biomed Res Int,,,True
3892a126c127795e96e4e071cf14fd7fdc2e4231,PMC,Inhibitory Effect of Matrine on Blood-Brain Barrier Disruption for the Treatment of Experimental Autoimmune Encephalomyelitis,http://dx.doi.org/10.1155/2013/736085,PMC3781841,24194630,CC BY,"Dysfunction of the blood-brain barrier (BBB) is a primary characteristic of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to suppress clinical EAE and CNS inflammation. However, whether this effect of MAT is through protecting the integrity and function of the BBB is not known. In the present study, we show that MAT treatment had a therapeutic effect comparable to dexamethasone (DEX) in EAE rats, with reduced Evans Blue extravasation, increased expression of collagen IV, the major component of the basement membrane, and the structure of tight junction (TJ) adaptor protein Zonula occludens-1 (ZO-1). Furthermore, MAT treatment attenuated expression of matrix metalloproteinase-9 and -2 (MMP-9/-2), while it increased the expression of tissue inhibitors of metalloproteinase-1 and -2 (TIMP-1/-2). Our findings demonstrate that MAT reduces BBB leakage by strengthening basement membrane, inhibiting activities of MMP-2 and -9, and upregulating their inhibitors. Taken together, our results identify a novel mechanism underlying the effect of MAT, a natural compound that could be a novel therapy for MS.",2013 Sep 8,"['Zhang, Su', 'Kan, Quan-Cheng', 'Xu, Yuming', 'Zhang, Guang-Xian', 'Zhu, Lin']",Mediators Inflamm,,,True
49f674332aef03ed0e231eaed321de8cb65b6644,PMC,"A Single Dose of Azithromycin Does Not Improve Clinical Outcomes of Children Hospitalised with Bronchiolitis: A Randomised, Placebo-Controlled Trial",http://dx.doi.org/10.1371/journal.pone.0074316,PMC3783434,24086334,CC BY,"OBJECTIVE: Bronchiolitis, one of the most common reasons for hospitalisation in young children, is particularly problematic in Indigenous children. Macrolides may be beneficial in settings where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness. The aim of our double-blind placebo-controlled randomised trial was to determine if a large single dose of azithromycin (compared to placebo) reduced length of stay (LOS), duration of oxygen (O(2)) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis. We also determined the effect of azithromycin on nasopharyngeal microbiology. METHODS: Children aged ≤18 months were randomised to receive a single large dose (30 mg/kg) of either azithromycin or placebo within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline and 48hrs later. Primary endpoints (LOS, O(2)) were monitored every 12 hrs. Hospitalised respiratory readmissions 6-months post discharge was collected. RESULTS: 97 children were randomised (n = 50 azithromycin, n = 47 placebo). Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58 hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O(2) requirement was not significantly different between groups; Azithromycin = 35 hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p = 0.8). At least one virus was detected in 74% of children. The azithromycin group had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in viral detection at 48 hours. CONCLUSION: Although a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS, duration of O(2) requirement or readmissions in children hospitalised with bronchiolitis. It remains uncertain if an earlier and/or longer duration of azithromycin improves clinical and microbiological outcomes for children. The trial was registered with the Australian and New Zealand Clinical Trials Register. Clinical trials number: ACTRN12608000150347. http://www.anzctr.org.au/TrialSearch.aspx.",2013 Sep 25,"['McCallum, Gabrielle B.', 'Morris, Peter S.', 'Chatfield, Mark D.', 'Maclennan, Carolyn', 'White, Andrew V.', 'Sloots, Theo P.', 'Mackay, Ian M.', 'Chang, Anne B.']",PLoS One,,,True
9caca240f207e4d98c2f98c7ec3818864afb8aeb,PMC,"A Single Dose of Azithromycin Does Not Improve Clinical Outcomes of Children Hospitalised with Bronchiolitis: A Randomised, Placebo-Controlled Trial",http://dx.doi.org/10.1371/journal.pone.0074316,PMC3783434,24086334,CC BY,"OBJECTIVE: Bronchiolitis, one of the most common reasons for hospitalisation in young children, is particularly problematic in Indigenous children. Macrolides may be beneficial in settings where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness. The aim of our double-blind placebo-controlled randomised trial was to determine if a large single dose of azithromycin (compared to placebo) reduced length of stay (LOS), duration of oxygen (O(2)) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis. We also determined the effect of azithromycin on nasopharyngeal microbiology. METHODS: Children aged ≤18 months were randomised to receive a single large dose (30 mg/kg) of either azithromycin or placebo within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline and 48hrs later. Primary endpoints (LOS, O(2)) were monitored every 12 hrs. Hospitalised respiratory readmissions 6-months post discharge was collected. RESULTS: 97 children were randomised (n = 50 azithromycin, n = 47 placebo). Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58 hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O(2) requirement was not significantly different between groups; Azithromycin = 35 hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p = 0.8). At least one virus was detected in 74% of children. The azithromycin group had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in viral detection at 48 hours. CONCLUSION: Although a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS, duration of O(2) requirement or readmissions in children hospitalised with bronchiolitis. It remains uncertain if an earlier and/or longer duration of azithromycin improves clinical and microbiological outcomes for children. The trial was registered with the Australian and New Zealand Clinical Trials Register. Clinical trials number: ACTRN12608000150347. http://www.anzctr.org.au/TrialSearch.aspx.",2013 Sep 25,"['McCallum, Gabrielle B.', 'Morris, Peter S.', 'Chatfield, Mark D.', 'Maclennan, Carolyn', 'White, Andrew V.', 'Sloots, Theo P.', 'Mackay, Ian M.', 'Chang, Anne B.']",PLoS One,,,False
fe5d9afd46890e2338d8d0febf8eaa8bd2166d60,PMC,"A Single Dose of Azithromycin Does Not Improve Clinical Outcomes of Children Hospitalised with Bronchiolitis: A Randomised, Placebo-Controlled Trial",http://dx.doi.org/10.1371/journal.pone.0074316,PMC3783434,24086334,CC BY,"OBJECTIVE: Bronchiolitis, one of the most common reasons for hospitalisation in young children, is particularly problematic in Indigenous children. Macrolides may be beneficial in settings where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness. The aim of our double-blind placebo-controlled randomised trial was to determine if a large single dose of azithromycin (compared to placebo) reduced length of stay (LOS), duration of oxygen (O(2)) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis. We also determined the effect of azithromycin on nasopharyngeal microbiology. METHODS: Children aged ≤18 months were randomised to receive a single large dose (30 mg/kg) of either azithromycin or placebo within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline and 48hrs later. Primary endpoints (LOS, O(2)) were monitored every 12 hrs. Hospitalised respiratory readmissions 6-months post discharge was collected. RESULTS: 97 children were randomised (n = 50 azithromycin, n = 47 placebo). Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58 hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O(2) requirement was not significantly different between groups; Azithromycin = 35 hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p = 0.8). At least one virus was detected in 74% of children. The azithromycin group had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in viral detection at 48 hours. CONCLUSION: Although a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS, duration of O(2) requirement or readmissions in children hospitalised with bronchiolitis. It remains uncertain if an earlier and/or longer duration of azithromycin improves clinical and microbiological outcomes for children. The trial was registered with the Australian and New Zealand Clinical Trials Register. Clinical trials number: ACTRN12608000150347. http://www.anzctr.org.au/TrialSearch.aspx.",2013 Sep 25,"['McCallum, Gabrielle B.', 'Morris, Peter S.', 'Chatfield, Mark D.', 'Maclennan, Carolyn', 'White, Andrew V.', 'Sloots, Theo P.', 'Mackay, Ian M.', 'Chang, Anne B.']",PLoS One,,,True
a462888bb4b9f31940fb166c07a8590406150575,PMC,Mucosal Vaccination with Recombinant Adenovirus Encoding Nucleoprotein Provides Potent Protection against Influenza Virus Infection,http://dx.doi.org/10.1371/journal.pone.0075460,PMC3783479,24086536,CC BY,"Influenza vaccines that target the highly variable surface glycoproteins hemagglutinin and neuraminidase cause inconvenience of having vaccination every year. For this reason, development of universal vaccines targeting conserved viral components is needed. In this study, we generated recombinant adenovirus (rAd) vaccine encoding nucleoprotein (NP) of A/PR/8/34 influenza virus, designated rAd/NP. BALB/c mice were immunized intranasally or sublingually with rAd/NP vaccine and subsequently challenged with lethal doses of heterologous as well as homologous influenza viruses. We found that intranasal immunization of rAd/NP elicited strong mucosal IgA responses as well as stronger CD8 T-cell responses toward immunodominant K(d)-restricted NP(147-155) epitope than sublingual immunization. Importantly, only single intranasal but not sublingual immunization of rAd/NP provides potent protection against both homologous and heterologous influenza virus challenges. These results suggest that recombinant rAd/NP could be a universal vaccine candidate for mucosal administration against influenza virus.",2013 Sep 25,"['Kim, So-Hee', 'Kim, Joo Young', 'Choi, Youngjoo', 'Nguyen, Huan H.', 'Song, Man Ki', 'Chang, Jun']",PLoS One,,,True
187062df058ff8a8110c008bc1f489986423ea1e,PMC,Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface,http://dx.doi.org/10.1371/journal.ppat.1003611,PMC3784481,24086132,CC BY,"Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.",2013 Sep 26,"['Juranic Lisnic, Vanda', 'Babic Cac, Marina', 'Lisnic, Berislav', 'Trsan, Tihana', 'Mefferd, Adam', 'Das Mukhopadhyay, Chitrangada', 'Cook, Charles H.', 'Jonjic, Stipan', 'Trgovcich, Joanne']",PLoS Pathog,,,True
edd69dd68ae88e3aeb94be5c0f963806b86e6d65,PMC,Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface,http://dx.doi.org/10.1371/journal.ppat.1003611,PMC3784481,24086132,CC BY,"Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.",2013 Sep 26,"['Juranic Lisnic, Vanda', 'Babic Cac, Marina', 'Lisnic, Berislav', 'Trsan, Tihana', 'Mefferd, Adam', 'Das Mukhopadhyay, Chitrangada', 'Cook, Charles H.', 'Jonjic, Stipan', 'Trgovcich, Joanne']",PLoS Pathog,,,False
54fc333fdf388bbf38305116d4971247a3681ca1,PMC,Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface,http://dx.doi.org/10.1371/journal.ppat.1003611,PMC3784481,24086132,CC BY,"Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.",2013 Sep 26,"['Juranic Lisnic, Vanda', 'Babic Cac, Marina', 'Lisnic, Berislav', 'Trsan, Tihana', 'Mefferd, Adam', 'Das Mukhopadhyay, Chitrangada', 'Cook, Charles H.', 'Jonjic, Stipan', 'Trgovcich, Joanne']",PLoS Pathog,,,False
601a89290b86adc02519f8d826eb7499e1ed152e,PMC,Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface,http://dx.doi.org/10.1371/journal.ppat.1003611,PMC3784481,24086132,CC BY,"Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.",2013 Sep 26,"['Juranic Lisnic, Vanda', 'Babic Cac, Marina', 'Lisnic, Berislav', 'Trsan, Tihana', 'Mefferd, Adam', 'Das Mukhopadhyay, Chitrangada', 'Cook, Charles H.', 'Jonjic, Stipan', 'Trgovcich, Joanne']",PLoS Pathog,,,False
b3490420de53f1b7bcaf510f6bcb562c1d6970c6,PMC,Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface,http://dx.doi.org/10.1371/journal.ppat.1003611,PMC3784481,24086132,CC BY,"Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.",2013 Sep 26,"['Juranic Lisnic, Vanda', 'Babic Cac, Marina', 'Lisnic, Berislav', 'Trsan, Tihana', 'Mefferd, Adam', 'Das Mukhopadhyay, Chitrangada', 'Cook, Charles H.', 'Jonjic, Stipan', 'Trgovcich, Joanne']",PLoS Pathog,,,False
d766ab43735b3ae26606a19ef9ddbe46c77fb24e,PMC,Complete Genome Sequence of a Novel Feline Astrovirus from a Domestic Cat in Hong Kong,http://dx.doi.org/10.1128/genomeA.00708-13,PMC3784778,24072858,CC BY,"We report the first complete genome sequence of a feline astrovirus (FAstV), FAstV2 strain 1637F, identified from a domestic cat. The genome is 6,779 nucleotides (nt) in length and consists of three overlapping open reading frames (ORF1a-ORF1b-ORF2). Sequence analysis suggests that FAstV2 represents a new FAstV genotype that is closely related to human astroviruses.",2013 Sep 26,"['Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Yip, Cyril C. Y.', 'Bai, Ru', 'Wu, Ying', 'Tse, Herman', 'Yuen, Kwok-yung']",Genome Announc,,,True
338d45deb88de8cc7f4cf5158c4752fb3533a0b7,PMC,Development of a New Resequencing Pathogen Microarray Based Assay for Detection of Broad-Spectrum Respiratory Tract Viruses in Patients with Community-Acquired Pneumonia,http://dx.doi.org/10.1371/journal.pone.0075704,PMC3785410,24086618,CC BY,"A Resequencing Pathogen Microarray (RPM) is a single, highly multiplexed assay for detecting and differentiating similarly related pathogens by using closely overlapping probe sets to determine a target organism’s nucleotide sequence. In this study, a new RPM (RPM-IVDC1) that consisted of 224-bp detector tiles corresponding to 9 influenza A subtypes, 11 rhinoviruses, 28 enteroviruses and 38 other respiratory viruses was developed and optimized to provide individual and simultaneous detection sensitivities ranging from 15 to 750 genomic copies for 16 common respiratory pathogens. A total of 110 consecutive patients with community-acquired pneumonia (CAP) admitted to 5 district general hospitals in Beijing during a 1-year period were assessed using the new assay. Among the children (under age 5) and adult patients (above age 18), respiratory syncytial virus (RSV) and rhinovirus (RV) were the most common etiological agents, respectively, which is consistent with reference assays. Atypical pathogens that may cause CAP-like illness, including rubella virus, measles virus, influenza type C virus, human herpesvirus (HHV) were also detected. The results show the capability of RPM-IVDC1 for the accurate detection and identification of multiple virus types, which may be of significant use in epidemic surveillance and outbreak investigations of atypical pathogens.",2013 Sep 27,"['Shen, Hongwei', 'Shi, Weixian', 'Wang, Ji', 'Wang, Miao', 'Li, Jin', 'Zhang, Chen', 'Nie, Kai', 'Yang, Mengjie', 'Zhang, Yi', 'Li, Aihua', 'Tan, Wenjie', 'Ma, Xuejun']",PLoS One,,,True
55b7d9b5320f9763edab4a3d32586bbf5dc2c487,PMC,The Potential of Metatranscriptomics for Identifying Screening Targets for Bacterial Vaginosis,http://dx.doi.org/10.1371/journal.pone.0076892,PMC3785445,24086764,CC BY,"BACKGROUND: The ribosomal RNA content of a sample collected from a woman with bacterial vaginosis (BV) was analysed to determine the active microbial community, and to identify potential targets for further screening. METHODOLOGY/PRINCIPAL FINDINGS: The sample from the BV patient underwent total RNA extraction, followed by physical subtraction of human rRNA and whole transcriptome amplification. The metatranscriptome was sequenced using Roche 454 titanium chemistry. The bioinformatics pipeline MG-RAST and desktop DNA analysis platforms were utilised to analyse results. Bacteria of the genus Prevotella (predominately P. amnii) constituted 36% of the 16S rRNA reads, followed by Megasphaera (19%), Leptotrichia/Sneathia (8%) and Fusobacterium (8%). Comparison of the abundances of several bacteria to quantitative PCR (qPCR) screening of extracted DNA revealed comparable relative abundances. This suggests a correlation between what was present and transcriptionally active in this sample: however distinct differences were seen when compared to the microbiome determined by 16S rRNA gene amplicon sequencing. To assess the presence of P. amnii in a larger pool of samples, 90 sexually active women were screened using qPCR. This bacterium was found to be strongly associated with BV (P<0.001, OR 23.3 (95%CI:2.9–190.7)) among the 90 women. CONCLUSIONS/SIGNIFICANCE: This study highlighted the potential of metatranscriptomics as a tool for characterising metabolically active microbiota and identifying targets for further screening. Prevotella amnii was chosen as an example target, being the most metabolically active species present in the single patient with BV, and was found to be detected at a high concentration by qPCR in 31% of cohort with BV, with an association with both oral and penile-vaginal sex.",2013 Sep 27,"['Twin, Jimmy', 'Bradshaw, Catriona S.', 'Garland, Suzanne M.', 'Fairley, Christopher K.', 'Fethers, Katherine', 'Tabrizi, Sepehr N.']",PLoS One,,,True
f56c5a350cc09b29ab51068039bfb27523945e09,PMC,Spatiotemporal Infectious Disease Modeling: A BME-SIR Approach,http://dx.doi.org/10.1371/journal.pone.0072168,PMC3785461,24086257,CC BY,"This paper is concerned with the modeling of infectious disease spread in a composite space-time domain under conditions of uncertainty. We focus on stochastic modeling that accounts for basic mechanisms of disease distribution and multi-sourced in situ uncertainties. Starting from the general formulation of population migration dynamics and the specification of transmission and recovery rates, the model studies the functional formulation of the evolution of the fractions of susceptible-infected-recovered individuals. The suggested approach is capable of: a) modeling population dynamics within and across localities, b) integrating the disease representation (i.e. susceptible-infected-recovered individuals) with observation time series at different geographical locations and other sources of information (e.g. hard and soft data, empirical relationships, secondary information), and c) generating predictions of disease spread and associated parameters in real time, while considering model and observation uncertainties. Key aspects of the proposed approach are illustrated by means of simulations (i.e. synthetic studies), and a real-world application using hand-foot-mouth disease (HFMD) data from China.",2013 Sep 27,"['Angulo, Jose', 'Yu, Hwa-Lung', 'Langousis, Andrea', 'Kolovos, Alexander', 'Wang, Jinfeng', 'Madrid, Ana Esther', 'Christakos, George']",PLoS One,,,True
74007d5a0dcfc70e0dbd281081f1408fed1a9116,PMC,Scoping Review on Search Queries and Social Media for Disease Surveillance: A Chronology of Innovation,http://dx.doi.org/10.2196/jmir.2740,PMC3785982,23896182,CC BY,"BACKGROUND: The threat of a global pandemic posed by outbreaks of influenza H5N1 (1997) and Severe Acute Respiratory Syndrome (SARS, 2002), both diseases of zoonotic origin, provoked interest in improving early warning systems and reinforced the need for combining data from different sources. It led to the use of search query data from search engines such as Google and Yahoo! as an indicator of when and where influenza was occurring. This methodology has subsequently been extended to other diseases and has led to experimentation with new types of social media for disease surveillance. OBJECTIVE: The objective of this scoping review was to formally assess the current state of knowledge regarding the use of search queries and social media for disease surveillance in order to inform future work on early detection and more effective mitigation of the effects of foodborne illness. METHODS: Structured scoping review methods were used to identify, characterize, and evaluate all published primary research, expert review, and commentary articles regarding the use of social media in surveillance of infectious diseases from 2002-2011. RESULTS: Thirty-two primary research articles and 19 reviews and case studies were identified as relevant. Most relevant citations were peer-reviewed journal articles (29/32, 91%) published in 2010-11 (28/32, 88%) and reported use of a Google program for surveillance of influenza. Only four primary research articles investigated social media in the context of foodborne disease or gastroenteritis. Most authors (21/32 articles, 66%) reported that social media-based surveillance had comparable performance when compared to an existing surveillance program. The most commonly reported strengths of social media surveillance programs included their effectiveness (21/32, 66%) and rapid detection of disease (21/32, 66%). The most commonly reported weaknesses were the potential for false positive (16/32, 50%) and false negative (11/32, 34%) results. Most authors (24/32, 75%) recommended that social media programs should primarily be used to support existing surveillance programs. CONCLUSIONS: The use of search queries and social media for disease surveillance are relatively recent phenomena (first reported in 2006). Both the tools themselves and the methodologies for exploiting them are evolving over time. While their accuracy, speed, and cost compare favorably with existing surveillance systems, the primary challenge is to refine the data signal by reducing surrounding noise. Further developments in digital disease surveillance have the potential to improve sensitivity and specificity, passively through advances in machine learning and actively through engagement of users. Adoption, even as supporting systems for existing surveillance, will entail a high level of familiarity with the tools and collaboration across jurisdictions.",2013 Jul 18,"['Bernardo, Theresa Marie', 'Rajic, Andrijana', 'Young, Ian', 'Robiadek, Katie', 'Pham, Mai T', 'Funk, Julie A']",J Med Internet Res,,,False
8f9f22f0d245cf41e5047230fa1c907b47a734ac,PMC,Virus-induced exacerbations in asthma and COPD,http://dx.doi.org/10.3389/fmicb.2013.00293,PMC3787546,24098299,CC BY,"Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and/or airflow limitation due to pulmonary emphysema. Chronic bronchitis, pulmonary emphysema, and bronchial asthma may all be associated with airflow limitation; therefore, exacerbation of asthma may be associated with the pathophysiology of COPD. Furthermore, recent studies have suggested that the exacerbation of asthma, namely virus-induced asthma, may be associated with a wide variety of respiratory viruses. COPD and asthma have different underlying pathophysiological processes and thus require individual therapies. Exacerbation of both COPD and asthma, which are basically defined and diagnosed by clinical symptoms, is associated with a rapid decline in lung function and increased mortality. Similar pathogens, including human rhinovirus, respiratory syncytial virus, influenza virus, parainfluenza virus, and coronavirus, are also frequently detected during exacerbation of asthma and/or COPD. Immune response to respiratory viral infections, which may be related to the severity of exacerbation in each disease, varies in patients with both COPD and asthma. In this regard, it is crucial to recognize and understand both the similarities and differences of clinical features in patients with COPD and/or asthma associated with respiratory viral infections, especially in the exacerbative stage. In relation to definition, epidemiology, and pathophysiology, this review aims to summarize current knowledge concerning exacerbation of both COPD and asthma by focusing on the clinical significance of associated respiratory virus infections.",2013 Oct 1,"['Kurai, Daisuke', 'Saraya, Takeshi', 'Ishii, Haruyuki', 'Takizawa, Hajime']",Front Microbiol,,,True
274eab479084dcb79951d6fdde012c9eab9bb469,PMC,Ligand Pose and Orientational Sampling in Molecular Docking,http://dx.doi.org/10.1371/journal.pone.0075992,PMC3787967,24098414,CC BY,"Molecular docking remains an important tool for structure-based screening to find new ligands and chemical probes. As docking ambitions grow to include new scoring function terms, and to address ever more targets, the reliability and extendability of the orientation sampling, and the throughput of the method, become pressing. Here we explore sampling techniques that eliminate stochastic behavior in DOCK3.6, allowing us to optimize the method for regularly variable sampling of orientations. This also enabled a focused effort to optimize the code for efficiency, with a three-fold increase in the speed of the program. This, in turn, facilitated extensive testing of the method on the 102 targets, 22,805 ligands and 1,411,214 decoys of the Directory of Useful Decoys - Enhanced (DUD-E) benchmarking set, at multiple levels of sampling. Encouragingly, we observe that as sampling increases from 50 to 500 to 2000 to 5000 to 20000 molecular orientations in the binding site (and so from about 1×10(10) to 4×10(10) to 1×10(11) to 2×10(11) to 5×10(11) mean atoms scored per target, since multiple conformations are sampled per orientation), the enrichment of ligands over decoys monotonically increases for most DUD-E targets. Meanwhile, including internal electrostatics in the evaluation ligand conformational energies, and restricting aromatic hydroxyls to low energy rotamers, further improved enrichment values. Several of the strategies used here to improve the efficiency of the code are broadly applicable in the field.",2013 Oct 1,"['Coleman, Ryan G.', 'Carchia, Michael', 'Sterling, Teague', 'Irwin, John J.', 'Shoichet, Brian K.']",PLoS One,,,True
33b590b2a517896a894c71c1c0b86c593804c034,PMC,"Use of a Safe, Reproducible, and Rapid Aerosol Delivery Method to Study Infection by Burkholderia pseudomallei and Burkholderia mallei in Mice",http://dx.doi.org/10.1371/journal.pone.0076804,PMC3788738,24098563,CC BY,"Burkholderia pseudomallei, the etiologic agent of melioidosis, is a saprophytic bacterium readily isolated from wet soils of countries bordering the equator. Burkholderia mallei is a host-adapted clone of B. pseudomallei that does not persist outside of its equine reservoir and causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by these organisms typically occurs via percutaneous inoculation or inhalation of aerosols, and the most common manifestation is severe pneumonia leading to fatal bacteremia. Glanders and melioidosis are difficult to diagnose and require prolonged antibiotic therapy with low success rates. There are no vaccines available to protect against either Burkholderia species, and there is concern regarding their use as biological warfare agents given that B. mallei has previously been utilized in this manner. Hence, experiments were performed to establish a mouse model of aerosol infection to study the organisms and develop countermeasures. Using a hand-held aerosolizer, BALB/c mice were inoculated intratracheally with strains B. pseudomallei 1026b and B. mallei ATCC23344 and growth of the agents in the lungs, as well as dissemination to the spleen, were examined. Mice infected with 10(2), 10(3) and 10(4) organisms were unable to control growth of B. mallei in the lungs and bacteria rapidly disseminated to the spleen. Though similar results were observed in mice inoculated with 10(3) and 10(4) B. pseudomallei cells, animals infected with 10(2) organisms controlled bacterial replication in the lungs, dissemination to the spleen, and the extent of bacteremia. Analysis of sera from mice surviving acute infection revealed that animals produced antibodies against antigens known to be targets of the immune response in humans. Taken together, these data show that small volume aerosol inoculation of mice results in acute disease, dose-dependent chronic infection, and immune responses that correlate with those seen in human infections.",2013 Oct 2,"['Lafontaine, Eric R.', 'Zimmerman, Shawn M.', 'Shaffer, Teresa L.', 'Michel, Frank', 'Gao, Xiudan', 'Hogan, Robert J.']",PLoS One,,,True
efba2008a6ccf1ad2614aebd79a6a741ea6538b9,PMC,Immunomodulatory Activity and Protective Effects of Polysaccharide from Eupatorium adenophorum Leaf Extract on Highly Pathogenic H5N1 Influenza Infection,http://dx.doi.org/10.1155/2013/194976,PMC3789439,24159339,CC BY,"The development of novel broad-spectrum, antiviral agents against H5N1 infection is urgently needed. In this study, we evaluated the immunomodulatory activities and protective effect of Eupatorium adenophorum polysaccharide (EAP) against the highly pathogenic H5N1 subtype influenza virus. EAP treatment significantly increased the production of IL-6, TNF-α, and IFN-γ both in vivo and in vitro as measured by qPCR and ELISA. In a mouse infection model, intranasal administration of EAP at a dose of 25 mg/kg body weight prior to H5N1 viral challenge efficiently inhibited viral replication, decreased lung lesions, and increased survival rate. We further evaluated the innate immune recognition of EAP, as this process is regulated primarily Dectin-1 and mannose receptor (MR). These results indicate that EAP may have immunomodulatory properties and a potential prophylactic effect against H5N1 influenza infection. Our investigation suggests an alternative strategy for the development of novel antiinfluenza agents and benefits of E. adenophorum products.",2013 Sep 18,"['Jin, Yi', 'Zhang, Yuewei', 'Wan, Chunyan', 'Wang, Hongjun', 'Hou, Lingyu', 'Chang, Jianyu', 'Fan, Kai', 'Xie, Xiangming']",Evid Based Complement Alternat Med,,,True
5c533a06c3dc5afefab5dd138ec4de394b537261,PMC,Role of the Spike Glycoprotein of Human Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Virus Entry and Syncytia Formation,http://dx.doi.org/10.1371/journal.pone.0076469,PMC3789674,24098509,CC BY,"Little is known about the biology of the emerging human group c betacoronavirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV). Because coronavirus spike glycoproteins (S) mediate virus entry, affect viral host range, and elicit neutralizing antibodies, analyzing the functions of MERS-CoV S protein is a high research priority. MERS-CoV S on lentivirus pseudovirions mediated entry into a variety of cell types including embryo cells from New World Eptesicus fuscus bats. Surprisingly, a polyclonal antibody to the S protein of MHV, a group a murine betacoronavirus, cross-reacted in immunoblots with the S2 domain of group c MERS-CoV spike protein. MERS pseudovirions released from 293T cells contained only uncleaved S, and pseudovirus entry was blocked by lysosomotropic reagents NH(4)Cl and bafilomycin and inhibitors of cathepsin L. However, when MERS pseudovirions with uncleaved S protein were adsorbed at 4°C to Vero E6 cells, brief trypsin treatment at neutral pH triggered virus entry at the plasma membrane and syncytia formation. When 293T cells producing MERS pseudotypes co-expressed serine proteases TMPRSS-2 or -4, large syncytia formed at neutral pH, and the pseudovirions produced were non-infectious and deficient in S protein. These experiments show that if S protein on MERS pseudovirions is uncleaved, then viruses enter by endocytosis in a cathepsin L-dependent manner, but if MERS-CoV S is cleaved, either during virus maturation by serine proteases or on pseudovirions by trypsin in extracellular fluids, then viruses enter at the plasma membrane at neutral pH and cause massive syncytia formation even in cells that express little or no MERS-CoV receptor. Thus, whether MERS-CoV enters cells within endosomes or at the plasma membrane depends upon the host cell type and tissue, and is determined by the location of host proteases that cleave the viral spike glycoprotein and activate membrane fusion.",2013 Oct 3,"['Qian, Zhaohui', 'Dominguez, Samuel R.', 'Holmes, Kathryn V.']",PLoS One,,,True
a6fc1b376a385d9f49f852a9f53e1e9149cb556a,PMC,Sequestration by IFIT1 Impairs Translation of 2′O-unmethylated Capped RNA,http://dx.doi.org/10.1371/journal.ppat.1003663,PMC3789756,24098121,CC BY,"Viruses that generate capped RNA lacking 2′O methylation on the first ribose are severely affected by the antiviral activity of Type I interferons. We used proteome-wide affinity purification coupled to mass spectrometry to identify human and mouse proteins specifically binding to capped RNA with different methylation states. This analysis, complemented with functional validation experiments, revealed that IFIT1 is the sole interferon-induced protein displaying higher affinity for unmethylated than for methylated capped RNA. IFIT1 tethers a species-specific protein complex consisting of other IFITs to RNA. Pulsed stable isotope labelling with amino acids in cell culture coupled to mass spectrometry as well as in vitro competition assays indicate that IFIT1 sequesters 2′O-unmethylated capped RNA and thereby impairs binding of eukaryotic translation initiation factors to 2′O-unmethylated RNA template, which results in inhibition of translation. The specificity of IFIT1 for 2′O-unmethylated RNA serves as potent antiviral mechanism against viruses lacking 2′O-methyltransferase activity and at the same time allows unperturbed progression of the antiviral program in infected cells.",2013 Oct 3,"['Habjan, Matthias', 'Hubel, Philipp', 'Lacerda, Livia', 'Benda, Christian', 'Holze, Cathleen', 'Eberl, Christian H.', 'Mann, Angelika', 'Kindler, Eveline', 'Gil-Cruz, Cristina', 'Ziebuhr, John', 'Thiel, Volker', 'Pichlmair, Andreas']",PLoS Pathog,,,True
a5cd1a73534959eff5332bcd3e5bc012f38c9137,PMC,Sensitive Detection of Viral Transcripts in Human Tumor Transcriptomes,http://dx.doi.org/10.1371/journal.pcbi.1003228,PMC3789765,24098097,CC BY,"In excess of [Image: see text]% of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses. We have developed a novel computational approach for detecting viral transcripts in human cancers that takes the aforementioned confounding factors into account and is applicable to a wide variety of viruses and tumors. We apply the approach to conducting the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The diverse clinical progression of this disease as well as related epidemiological and virological findings are highly suggestive of a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently contested. We mapped [Image: see text] transcriptomes of neuroblastoma as well as positive and negative controls to the human and all known viral genomes in order to detect both known and unknown viruses. Analysis of controls, comparisons with related methods, and statistical estimates demonstrate the high sensitivity of our approach. Detailed investigation of putative viral transcripts within neuroblastoma samples did not provide evidence for the existence of any known human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts did not result in expression signatures associated with novel human pathogens. While confounding factors such as sample dilution or viral clearance in progressed tumors may mask viral cofactors in the data, in principle, this is rendered less likely by the high sensitivity of our approach and the number of biological replicates analyzed. Therefore, our results suggest that frequent viral cofactors of metastatic neuroblastoma are unlikely.",2013 Oct 3,"['Schelhorn, Sven-Eric', 'Fischer, Matthias', 'Tolosi, Laura', 'Altmüller, Janine', 'Nürnberg, Peter', 'Pfister, Herbert', 'Lengauer, Thomas', 'Berthold, Frank']",PLoS Comput Biol,,,True
cabe96ceeaf4de3ad158c2579936a1ff3dfa352d,PMC,Ligand Clouds around Protein Clouds: A Scenario of Ligand Binding with Intrinsically Disordered Proteins,http://dx.doi.org/10.1371/journal.pcbi.1003249,PMC3789766,24098099,CC BY,"Intrinsically disordered proteins (IDPs) were found to be widely associated with human diseases and may serve as potential drug design targets. However, drug design targeting IDPs is still in the very early stages. Progress in drug design is usually achieved using experimental screening; however, the structural disorder of IDPs makes it difficult to characterize their interaction with ligands using experiments alone. To better understand the structure of IDPs and their interactions with small molecule ligands, we performed extensive simulations on the c-Myc(370–409) peptide and its binding to a reported small molecule inhibitor, ligand 10074-A4. We found that the conformational space of the apo c-Myc(370–409) peptide was rather dispersed and that the conformations of the peptide were stabilized mainly by charge interactions and hydrogen bonds. Under the binding of the ligand, c-Myc(370–409) remained disordered. The ligand was found to bind to c-Myc(370–409) at different sites along the chain and behaved like a ‘ligand cloud’. In contrast to ligand binding to more rigid target proteins that usually results in a dominant bound structure, ligand binding to IDPs may better be described as ligand clouds around protein clouds. Nevertheless, the binding of the ligand and a non-ligand to the c-Myc(370–409) target could be clearly distinguished. The present study provides insights that will help improve rational drug design that targets IDPs.",2013 Oct 3,"['Jin, Fan', 'Yu, Chen', 'Lai, Luhua', 'Liu, Zhirong']",PLoS Comput Biol,,,True
a49651276ae7cd5bf402c1066944fb7cfc83ffaa,PMC,Contribution of Host Intracellular Transport Machineries to Intercellular Movement of Turnip Mosaic Virus,http://dx.doi.org/10.1371/journal.ppat.1003683,PMC3789768,24098128,CC BY,"The contribution of different host cell transport systems in the intercellular movement of turnip mosaic virus (TuMV) was investigated. To discriminate between primary infections and secondary infections associated with the virus intercellular movement, a gene cassette expressing GFP-HDEL was inserted adjacent to a TuMV infectious cassette expressing 6K(2):mCherry, both within the T-DNA borders of the binary vector pCambia. In this system, both gene cassettes were delivered to the same cell by a single binary vector and primary infection foci emitted green and red fluorescence while secondarily infected cells emitted only red fluorescence. Intercellular movement was measured at 72 hours post infiltration and was estimated to proceed at an average rate of one cell being infected every three hours over an observation period of 17 hours. To determine if the secretory pathway were important for TuMV intercellular movement, chemical and protein inhibitors that blocked both early and late secretory pathways were used. Treatment with Brefeldin A or Concanamycin A or expression of ARF1 or RAB-E1d dominant negative mutants, all of which inhibit pre- or post-Golgi transport, reduced intercellular movement by the virus. These treatments, however, did not inhibit virus replication in primary infected cells. Pharmacological interference assays using Tyrphostin A23 or Wortmannin showed that endocytosis was not important for TuMV intercellular movement. Lack of co-localization by endocytosed FM4-64 and Ara7 (AtRabF2b) with TuMV-induced 6K(2)-tagged vesicles further supported this conclusion. Microfilament depolymerizing drugs and silencing expression of myosin XI-2 gene, but not myosin VIII genes, also inhibited TuMV intercellular movement. Expression of dominant negative myosin mutants confirmed the role played by myosin XI-2 as well as by myosin XI-K in TuMV intercellular movement. Using this dual gene cassette expression system and transport inhibitors, components of the secretory and actomyosin machinery were shown to be important for TuMV intercellular spread.",2013 Oct 3,"['Agbeci, Maxime', 'Grangeon, Romain', 'Nelson, Richard S.', 'Zheng, Huanquan', 'Laliberté, Jean-François']",PLoS Pathog,,,True
9c35a7f4d301162bfc79c1d7174a234ab94c2c46,PMC,Effect of the Plasmid-DNA Vaccination on Macroscopic and Microscopic Damage Caused by the Experimental Chronic Trypanosoma cruzi Infection in the Canine Model,http://dx.doi.org/10.1155/2013/826570,PMC3791577,24163822,CC BY,"The dog is considered the main domestic reservoir for Trypanosoma cruzi infection and a suitable experimental animal model to study the pathological changes during the course of Chagas disease (CD). Vaccine development is one of CD prevention methods to protect people at risk. Two plasmids containing genes encoding a trans-sialidase protein (TcSP) and an amastigote-specific glycoprotein (TcSSP4) were used as DNA vaccines in a canine model. Splenomegaly was not found in either of the recombinant plasmid-immunized groups; however, cardiomegaly was absent in animals immunized only with the plasmid containing the TcSSP4 gene. The inflammation of subendocardial and myocardial tissues was prevented only with the immunization with TcSSP4 gene. In conclusion, the vaccination with these genes has a partial protective effect on the enlargement of splenic and cardiac tissues during the chronic CD and on microscopic hearth damage, since both plasmids prevented splenomegaly but only one avoided cardiomegaly, and the lesions in heart tissue of dog immunized with plasmid containing the TcSSP4 gene covered only subepicardial tissue.",2013 Sep 19,"['Rodríguez-Morales, Olivia', 'Carrillo-Sánchez, Silvia C.', 'García-Mendoza, Humberto', 'Aranda-Fraustro, Alberto', 'Ballinas-Verdugo, Martha A.', 'Alejandre-Aguilar, Ricardo', 'Rosales-Encina, José Luis', 'Vallejo, Maite', 'Arce-Fonseca, Minerva']",Biomed Res Int,,,True
ca46ca49c4bf5dd684e066f5674cc980b7afb0a5,PMC,Comparative Serological Assays for the Study of H5 and H7 Avian Influenza Viruses,http://dx.doi.org/10.1155/2013/286158,PMC3791816,24163763,CC BY,"The nature of influenza virus to randomly mutate and evolve into new types is an important challenge in the control of influenza infection. It is necessary to monitor virus evolution for a better understanding of the pandemic risk posed by certain variants as evidenced by the highly pathogenic avian influenza (HPAI) viruses. This has been clearly recognized in Egypt following the notification of the first HPAI H5N1 outbreak. The continuous circulation of the virus and the mass vaccination programme undertaken in poultry have resulted in a progressive genetic evolution and a significant antigenic drift near the major antigenic sites. In order to establish if vaccination is sufficient to provide significant intra- and interclade cross-protection, lentiviral pseudotypes derived from H5N1 HPAI viruses (A/Vietnam/1194/04, A/chicken/Egypt-1709-01/2007) and an antigenic drift variant (A/chicken/Egypt-1709-06-2008) were constructed and used in pseudotype-based neutralization assays (pp-NT). pp-NT data obtained was confirmed and correlated with HI and MN assays. A panel of pseudotypes belonging to influenza Groups 1 and 2, with a combination of reporter systems, was also employed for testing avian sera in order to support further application of pp-NT as an alternative valid assay that can improve avian vaccination efficacy testing, vaccine virus selection, and the reliability of reference sera.",2013 Sep 15,"['Molesti, Eleonora', 'Milani, Adelaide', 'Terregino, Calogero', 'Cattoli, Giovanni', 'Temperton, Nigel J.']",Influenza Res Treat,,,True
e0c998049a9e7640184eeee597c13d35a43ccfef,PMC,iSNO-AAPair: incorporating amino acid pairwise coupling into PseAAC for predicting cysteine S-nitrosylation sites in proteins,http://dx.doi.org/10.7717/peerj.171,PMC3792191,24109555,CC BY,"As one of the most important and universal posttranslational modifications (PTMs) of proteins, S-nitrosylation (SNO) plays crucial roles in a variety of biological processes, including the regulation of cellular dynamics and many signaling events. Knowledge of SNO sites in proteins is very useful for drug development and basic research as well. Unfortunately, it is both time-consuming and costly to determine the SNO sites purely based on biological experiments. Facing the explosive protein sequence data generated in the post-genomic era, we are challenged to develop automated vehicles for timely and effectively determining the SNO sites for uncharacterized proteins. To address the challenge, a new predictor called iSNO-AAPair was developed by taking into account the coupling effects for all the pairs formed by the nearest residues and the pairs by the next nearest residues along protein chains. The cross-validation results on a state-of-the-art benchmark have shown that the new predictor outperformed the existing predictors. The same was true when tested by the independent proteins whose experimental SNO sites were known. A user-friendly web-server for iSNO-AAPair was established at http://app.aporc.org/iSNO-AAPair/, by which users can easily obtain their desired results without the need to follow the mathematical equations involved during its development.",2013 Oct 3,"['Xu, Yan', 'Shao, Xiao-Jian', 'Wu, Ling-Yun', 'Deng, Nai-Yang', 'Chou, Kuo-Chen']",PeerJ,,,False
a45bf1e6e622e9e69cc38fc265e2cf4d75bf51a4,PMC,iSNO-AAPair: incorporating amino acid pairwise coupling into PseAAC for predicting cysteine S-nitrosylation sites in proteins,http://dx.doi.org/10.7717/peerj.171,PMC3792191,24109555,CC BY,"As one of the most important and universal posttranslational modifications (PTMs) of proteins, S-nitrosylation (SNO) plays crucial roles in a variety of biological processes, including the regulation of cellular dynamics and many signaling events. Knowledge of SNO sites in proteins is very useful for drug development and basic research as well. Unfortunately, it is both time-consuming and costly to determine the SNO sites purely based on biological experiments. Facing the explosive protein sequence data generated in the post-genomic era, we are challenged to develop automated vehicles for timely and effectively determining the SNO sites for uncharacterized proteins. To address the challenge, a new predictor called iSNO-AAPair was developed by taking into account the coupling effects for all the pairs formed by the nearest residues and the pairs by the next nearest residues along protein chains. The cross-validation results on a state-of-the-art benchmark have shown that the new predictor outperformed the existing predictors. The same was true when tested by the independent proteins whose experimental SNO sites were known. A user-friendly web-server for iSNO-AAPair was established at http://app.aporc.org/iSNO-AAPair/, by which users can easily obtain their desired results without the need to follow the mathematical equations involved during its development.",2013 Oct 3,"['Xu, Yan', 'Shao, Xiao-Jian', 'Wu, Ling-Yun', 'Deng, Nai-Yang', 'Chou, Kuo-Chen']",PeerJ,,,False
951d9485254b93d47b0f2de99c4437966f1f202b,PMC,iSNO-AAPair: incorporating amino acid pairwise coupling into PseAAC for predicting cysteine S-nitrosylation sites in proteins,http://dx.doi.org/10.7717/peerj.171,PMC3792191,24109555,CC BY,"As one of the most important and universal posttranslational modifications (PTMs) of proteins, S-nitrosylation (SNO) plays crucial roles in a variety of biological processes, including the regulation of cellular dynamics and many signaling events. Knowledge of SNO sites in proteins is very useful for drug development and basic research as well. Unfortunately, it is both time-consuming and costly to determine the SNO sites purely based on biological experiments. Facing the explosive protein sequence data generated in the post-genomic era, we are challenged to develop automated vehicles for timely and effectively determining the SNO sites for uncharacterized proteins. To address the challenge, a new predictor called iSNO-AAPair was developed by taking into account the coupling effects for all the pairs formed by the nearest residues and the pairs by the next nearest residues along protein chains. The cross-validation results on a state-of-the-art benchmark have shown that the new predictor outperformed the existing predictors. The same was true when tested by the independent proteins whose experimental SNO sites were known. A user-friendly web-server for iSNO-AAPair was established at http://app.aporc.org/iSNO-AAPair/, by which users can easily obtain their desired results without the need to follow the mathematical equations involved during its development.",2013 Oct 3,"['Xu, Yan', 'Shao, Xiao-Jian', 'Wu, Ling-Yun', 'Deng, Nai-Yang', 'Chou, Kuo-Chen']",PeerJ,,,False
7de170f92a16c989329781224d8616189e55d598,PMC,iSNO-AAPair: incorporating amino acid pairwise coupling into PseAAC for predicting cysteine S-nitrosylation sites in proteins,http://dx.doi.org/10.7717/peerj.171,PMC3792191,24109555,CC BY,"As one of the most important and universal posttranslational modifications (PTMs) of proteins, S-nitrosylation (SNO) plays crucial roles in a variety of biological processes, including the regulation of cellular dynamics and many signaling events. Knowledge of SNO sites in proteins is very useful for drug development and basic research as well. Unfortunately, it is both time-consuming and costly to determine the SNO sites purely based on biological experiments. Facing the explosive protein sequence data generated in the post-genomic era, we are challenged to develop automated vehicles for timely and effectively determining the SNO sites for uncharacterized proteins. To address the challenge, a new predictor called iSNO-AAPair was developed by taking into account the coupling effects for all the pairs formed by the nearest residues and the pairs by the next nearest residues along protein chains. The cross-validation results on a state-of-the-art benchmark have shown that the new predictor outperformed the existing predictors. The same was true when tested by the independent proteins whose experimental SNO sites were known. A user-friendly web-server for iSNO-AAPair was established at http://app.aporc.org/iSNO-AAPair/, by which users can easily obtain their desired results without the need to follow the mathematical equations involved during its development.",2013 Oct 3,"['Xu, Yan', 'Shao, Xiao-Jian', 'Wu, Ling-Yun', 'Deng, Nai-Yang', 'Chou, Kuo-Chen']",PeerJ,,,False
35cf9c43b3b1028de85e24946f7bbc0436b24190,PMC,iSNO-AAPair: incorporating amino acid pairwise coupling into PseAAC for predicting cysteine S-nitrosylation sites in proteins,http://dx.doi.org/10.7717/peerj.171,PMC3792191,24109555,CC BY,"As one of the most important and universal posttranslational modifications (PTMs) of proteins, S-nitrosylation (SNO) plays crucial roles in a variety of biological processes, including the regulation of cellular dynamics and many signaling events. Knowledge of SNO sites in proteins is very useful for drug development and basic research as well. Unfortunately, it is both time-consuming and costly to determine the SNO sites purely based on biological experiments. Facing the explosive protein sequence data generated in the post-genomic era, we are challenged to develop automated vehicles for timely and effectively determining the SNO sites for uncharacterized proteins. To address the challenge, a new predictor called iSNO-AAPair was developed by taking into account the coupling effects for all the pairs formed by the nearest residues and the pairs by the next nearest residues along protein chains. The cross-validation results on a state-of-the-art benchmark have shown that the new predictor outperformed the existing predictors. The same was true when tested by the independent proteins whose experimental SNO sites were known. A user-friendly web-server for iSNO-AAPair was established at http://app.aporc.org/iSNO-AAPair/, by which users can easily obtain their desired results without the need to follow the mathematical equations involved during its development.",2013 Oct 3,"['Xu, Yan', 'Shao, Xiao-Jian', 'Wu, Ling-Yun', 'Deng, Nai-Yang', 'Chou, Kuo-Chen']",PeerJ,,,True
01110a24b6ce133ae80d21a36c7994e364ba296c,PMC,Feature Selection Methods for Identifying Genetic Determinants of Host Species in RNA Viruses,http://dx.doi.org/10.1371/journal.pcbi.1003254,PMC3794897,24130470,CC BY,"Despite environmental, social and ecological dependencies, emergence of zoonotic viruses in human populations is clearly also affected by genetic factors which determine cross-species transmission potential. RNA viruses pose an interesting case study given their mutation rates are orders of magnitude higher than any other pathogen – as reflected by the recent emergence of SARS and Influenza for example. Here, we show how feature selection techniques can be used to reliably classify viral sequences by host species, and to identify the crucial minority of host-specific sites in pathogen genomic data. The variability in alleles at those sites can be translated into prediction probabilities that a particular pathogen isolate is adapted to a given host. We illustrate the power of these methods by: 1) identifying the sites explaining SARS coronavirus differences between human, bat and palm civet samples; 2) showing how cross species jumps of rabies virus among bat populations can be readily identified; and 3) de novo identification of likely functional influenza host discriminant markers.",2013 Oct 10,"['Aguas, Ricardo', 'Ferguson, Neil M.']",PLoS Comput Biol,,,True
70943b05f17f2b7620ca6cc063b95ba2d7e8aab3,PMC,"Evaluation of the Replication, Pathogenicity, and Immunogenicity of Avian Paramyxovirus (APMV) Serotypes 2, 3, 4, 5, 7, and 9 in Rhesus Macaques",http://dx.doi.org/10.1371/journal.pone.0075456,PMC3794941,24130713,CC0,"Avian paramyxoviruses (APMV) serotypes 1–9 are frequently isolated from domestic and wild birds worldwide. APMV-1 (also called Newcastle disease virus, NDV) is attenuated in non-human primates and is being developed as a candidate human vaccine vector. The vector potential of the other serotypes was unknown. In the present study, we evaluated nine different biologically- or recombinantly-derived APMV strains for the ability to replicate and cause disease in rhesus macaque model. Five of the viruses were: biologically-derived wild type (wt) APMV-2, -3, -5, -7 and -9. Another virus was a recombinant (r) version of wt APMV-4. The remaining three viruses were versions of wt rAPMV-2, -4 and -7 in which the F cleavage site had been modified to be multi-basic. Rhesus macaques were inoculated intranasally and intratracheally and monitored for clinical disease, virus shedding from the upper and lower respiratory tract, and seroconversion. Virus shedding was not detected for wt APMV-5. Very limited shedding was detected for wt rAPMV-4 and modified rAPMV-4, and only in a subset of animals. Shedding by the other viruses was detected in every infected animal, and usually from both the upper and lower respiratory tract. In particular, shedding over a number of days in every animal was observed for modified rAPMV-2, wt APMV-7, and modified rAPMV-7. Modification of the F protein cleavage site appeared to increase shedding by wt rAPMV-2 and marginally by wt rAPMV-4. All APMVs except wt APMV-5 induced a virus-specific serum antibody response in all infected animals. None of the animals exhibited any clinical disease signs. These results indicate that APMVs 2, 3, 4, 7, and 9 are competent to infect non-human primates, but are moderately-to-highly restricted, depending on the serotype. This suggests that they are not likely to significantly infect primates in nature, and represent promising attenuated candidates for vector development.",2013 Oct 10,"['Khattar, Sunil K.', 'Nayak, Baibaswata', 'Kim, Shin-Hee', 'Xiao, Sa', 'Samal, Sweety', 'Paldurai, Anandan', 'Buchholz, Ursula J.', 'Collins, Peter L.', 'Samal, Siba K.']",PLoS One,,,True
bdb16338832867fb4c294b2694e8e23da78f3597,PMC,Caspase-1 Promotes Epstein-Barr Virus Replication by Targeting the Large Tegument Protein Deneddylase to the Nucleus of Productively Infected Cells,http://dx.doi.org/10.1371/journal.ppat.1003664,PMC3795028,24130483,CC BY,"The large tegument proteins of herpesviruses contain N-terminal cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but the function of the enzymes during virus replication remains largely unknown. Using as model BPLF1, the homologue encoded by Epstein-Barr virus (EBV), we found that induction of the productive virus cycle does not affect the total level of ubiquitin-conjugation but is accompanied by a BPLF1-dependent decrease of NEDD8-adducts and accumulation of free NEDD8. Expression of BPLF1 promotes cullin degradation and the stabilization of cullin-RING ligases (CRLs) substrates in the nucleus, while cytoplasmic CRLs and their substrates are not affected. The inactivation of nuclear CRLs is reversed by the N-terminus of CAND1, which inhibits the binding of BPLF1 to cullins and prevents efficient viral DNA replication. Targeting of the deneddylase activity to the nucleus is dependent on processing of the catalytic N-terminus by caspase-1. Inhibition of caspase-1 severely impairs viral DNA synthesis and the release of infectious virus, pointing a previously unrecognized role of the cellular response to danger signals triggered by EBV reactivation in promoting virus replication.",2013 Oct 10,"['Gastaldello, Stefano', 'Chen, Xinsong', 'Callegari, Simone', 'Masucci, Maria G.']",PLoS Pathog,,,True
7dbdecefcd59460800cc11324be0595779ffde80,PMC,Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody,http://dx.doi.org/10.1371/journal.ppat.1003684,PMC3795035,24130486,CC0,"The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines.",2013 Oct 10,"['Xu, Kai', 'Rockx, Barry', 'Xie, Yihu', 'DeBuysscher, Blair L.', 'Fusco, Deborah L.', 'Zhu, Zhongyu', 'Chan, Yee-Peng', 'Xu, Yan', 'Luu, Truong', 'Cer, Regina Z.', 'Feldmann, Heinz', 'Mokashi, Vishwesh', 'Dimitrov, Dimiter S.', 'Bishop-Lilly, Kimberly A.', 'Broder, Christopher C.', 'Nikolov, Dimitar B.']",PLoS Pathog,,,True
06c949be75a56cbb6228368dec7580bfbb638141,PMC,Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody,http://dx.doi.org/10.1371/journal.ppat.1003684,PMC3795035,24130486,CC0,"The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines.",2013 Oct 10,"['Xu, Kai', 'Rockx, Barry', 'Xie, Yihu', 'DeBuysscher, Blair L.', 'Fusco, Deborah L.', 'Zhu, Zhongyu', 'Chan, Yee-Peng', 'Xu, Yan', 'Luu, Truong', 'Cer, Regina Z.', 'Feldmann, Heinz', 'Mokashi, Vishwesh', 'Dimitrov, Dimiter S.', 'Bishop-Lilly, Kimberly A.', 'Broder, Christopher C.', 'Nikolov, Dimitar B.']",PLoS Pathog,,,False
2064f80647340c485e6143344cfe4223e8b08e2d,PMC,Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody,http://dx.doi.org/10.1371/journal.ppat.1003684,PMC3795035,24130486,CC0,"The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines.",2013 Oct 10,"['Xu, Kai', 'Rockx, Barry', 'Xie, Yihu', 'DeBuysscher, Blair L.', 'Fusco, Deborah L.', 'Zhu, Zhongyu', 'Chan, Yee-Peng', 'Xu, Yan', 'Luu, Truong', 'Cer, Regina Z.', 'Feldmann, Heinz', 'Mokashi, Vishwesh', 'Dimitrov, Dimiter S.', 'Bishop-Lilly, Kimberly A.', 'Broder, Christopher C.', 'Nikolov, Dimitar B.']",PLoS Pathog,,,False
221e182716d5ecbba8538ec7fda997030bc173c7,PMC,Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody,http://dx.doi.org/10.1371/journal.ppat.1003684,PMC3795035,24130486,CC0,"The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines.",2013 Oct 10,"['Xu, Kai', 'Rockx, Barry', 'Xie, Yihu', 'DeBuysscher, Blair L.', 'Fusco, Deborah L.', 'Zhu, Zhongyu', 'Chan, Yee-Peng', 'Xu, Yan', 'Luu, Truong', 'Cer, Regina Z.', 'Feldmann, Heinz', 'Mokashi, Vishwesh', 'Dimitrov, Dimiter S.', 'Bishop-Lilly, Kimberly A.', 'Broder, Christopher C.', 'Nikolov, Dimitar B.']",PLoS Pathog,,,False
f2df4fc3c60338755fd23da3d7e01c0455e20745,PMC,Complete Genome Sequence of a Nephropathogenic Infectious Bronchitis Virus Strain Isolated in China,http://dx.doi.org/10.1128/genomeA.00815-13,PMC3795213,24115543,CC BY,"Infectious bronchitis virus (IBV) causes tremendous economic losses to the poultry industry. Here, we report the complete genome analysis results for a new natural recombination nephropathogenic IBV strain named SAIBK, which was isolated in the Sichuan province of China in 2005.",2013 Oct 10,"['Yang, Jing-tian', 'Ma, Bing-cun']",Genome Announc,,,True
5143bcbf109f693de355d2512a5810ed93a3072a,PMC,Exploring a Proposed WHO Method to Determine Thresholds for Seasonal Influenza Surveillance,http://dx.doi.org/10.1371/journal.pone.0077244,PMC3795663,24146973,CC BY,"INTRODUCTION: Health authorities find thresholds useful to gauge the start and severity of influenza seasons. We explored a method for deriving thresholds proposed in an influenza surveillance manual published by the World Health Organization (WHO). METHODS: For 2002-2011, we analysed two routine influenza-like-illness (ILI) datasets, general practice sentinel surveillance and a locum medical service sentinel surveillance, plus laboratory data and hospital admissions for influenza. For each sentinel dataset, we created two composite variables from the product of weekly ILI data and the relevant laboratory data, indicating the proportion of tested specimens that were positive. For all datasets, including the composite datasets, we aligned data on the median week of peak influenza or ILI activity and assigned three threshold levels: seasonal threshold, determined by inspection; and two intensity thresholds termed average and alert thresholds, determined by calculations of means, medians, confidence intervals (CI) and percentiles. From the thresholds, we compared the seasonal onset, end and intensity across all datasets from 2002-2011. Correlation between datasets was assessed using the mean correlation coefficient. RESULTS: The median week of peak activity was week 34 for all datasets, except hospital data (week 35). Means and medians were comparable and the 90% upper CIs were similar to the 95(th) percentiles. Comparison of thresholds revealed variations in defining the start of a season but good agreement in describing the end and intensity of influenza seasons, except in hospital admissions data after the pandemic year of 2009. The composite variables improved the agreements between the ILI and other datasets. Datasets were well correlated, with mean correlation coefficients of >0.75 for a range of combinations. CONCLUSIONS: Thresholds for influenza surveillance are easily derived from historical surveillance and laboratory data using the approach proposed by WHO. Use of composite variables is helpful for describing influenza season characteristics.",2013 Oct 11,"['Tay, Ee Laine', 'Grant, Kristina', 'Kirk, Martyn', 'Mounts, Anthony', 'Kelly, Heath']",PLoS One,,,True
46ffe37cdfe520a31dadf0a3308b1f7f98d4295d,PMC,Targeted Deletion of FGL2 Leads to Increased Early Viral Replication and Enhanced Adaptive Immunity in a Murine Model of Acute Viral Hepatitis Caused by LCMV WE,http://dx.doi.org/10.1371/journal.pone.0072309,PMC3795679,24146739,CC BY,"Mounting effective innate and adaptive immune responses are critical for viral clearance and the generation of long lasting immunity. It is known that production of inhibitory factors may result in the inability of the host to clear viruses, resulting in chronic viral persistence. Fibrinogen-like protein 2 (FGL2) has been identified as a novel effector molecule of CD4(+)CD25(+) Foxp3(+) regulatory T (Treg) cells that inhibits immune activity by binding to FCγRIIB expressed primarily on antigen presenting cells (APC). In this study, we show that infection of mice with Lymphocytic Choriomeningitis Virus WE (LCMV WE) leads to increased plasma levels of FGL2, which were detected as early as 2 days post-infection (pi) and persisted until day 50 pi. Mice deficient in FGL2 (fgl2(−/−)) had increased viral titers of LCMV WE in the liver early p.i but cleared the virus by day 12 similar to wild type mice. Dendritic cells (DC) isolated from the spleens of LCMV WE infected fgl2(−/−) had increased expression of the DC maturation markers CD80 and MHC Class II compared to wild type (fgl2(+/+)). Frequencies of CD8(+) and CD4(+) T cells producing IFNγ in response to ex vivo peptide re-stimulation isolated from the spleen and lymph nodes were also increased in LCMV WE infected fgl2 (−/−) mice. Increased frequencies of CD8(+) T cells specific for LCMV tetramers GP(33) and NP(396) were detected within the liver of fgl2(−/−) mice. Plasma from fgl2(−/−) mice contained higher titers of total and neutralizing anti-LCMV antibody. Enhanced anti-viral immunity in fgl2(−/−) mice was associated with increased levels of serum alanine transaminase (ALT), hepatic necrosis and inflammation following LCMV WE infection. These data demonstrate that targeting FGL2 leads to early increased viral replication but enhanced anti-viral adaptive T & B cell responses. Targeting FGL2 may enhance the efficacy of current anti-viral therapies for hepatotropic viruses.",2013 Oct 11,"['Khattar, Ramzi', 'Luft, Olga', 'Yavorska, Nataliya', 'Shalev, Itay', 'Phillips, M. James', 'Adeyi, Oyedele', 'Gao, Darrin', 'Bartczak, Agata', 'Urbanellis, Peter', 'Shyu, Wendy', 'Zhang, Jianhua', 'Manuel, Justin', 'Levy, Gary A.', 'Selzner, Nazia']",PLoS One,,,True
2fd0fccb43ad3cb1634370734ba27eaed2cf015a,PMC,Caveolin-1 Associated Adenovirus Entry into Human Corneal Cells,http://dx.doi.org/10.1371/journal.pone.0077462,PMC3795695,24147000,CC BY,"The cellular entry of viruses represents a critical area of study, not only for viral tropism, but also because viral entry dictates the nature of the immune response elicited upon infection. Epidemic keratoconjunctivitis (EKC), caused by viruses within human adenovirus species D (HAdV-D), is a severe, ocular surface infection associated with corneal inflammation. Clathrin-mediated endocytosis has previously been shown to play a critical role in entry of other HAdV species into many host cell types. However, HAdV-D endocytosis into corneal cells has not been extensively studied. Herein, we show an essential role for cholesterol rich, lipid raft microdomains and caveolin-1, in the entry of HAdV-D37 into primary human corneal fibroblasts. Cholesterol depletion using methyl-β-cyclodextrin (MβCD) profoundly reduced viral infection. When replenished with soluble cholesterol, the effect of MβCD was reversed, allowing productive viral infection. HAdV-D37 DNA was identified in caveolin-1 rich endosomal fractions after infection. Src kinase activity was also increased in caveolin-1 rich endosomal fractions after infection, and Src phosphorylation and CXCL1 induction were both decreased in caveolin-1-/- mice corneas compared to wild type mice. siRNA knock down of caveolin-1 in corneal cells reduced chemokine induction upon viral infection, and caveolin-1-/- mouse corneas showed reduced cellular entry of HAdV-D37. As a control, HAdV-C2, a non-corneal pathogen, appeared to utilize the caveolar pathway for entry into A549 cells, but failed to infect corneal cells entirely, indicating virus and cell specific tropism. Immuno-electron microscopy confirmed the presence of caveolin-1 in HAdV-D37-containing vesicles during the earliest stages of viral entry. Collectively, these experiments indicate for the first time that HAdV-D37 uses a lipid raft mediated caveolin-1 associated pathway for entry into corneal cells, and connects the processes of viral entry with downstream proinflammatory cell signaling.",2013 Oct 11,"['Yousuf, Mohammad A.', 'Zhou, Xiaohong', 'Mukherjee, Santanu', 'Chintakuntlawar, Ashish V.', 'Lee, Jeong Yoon', 'Ramke, Mirja', 'Chodosh, James', 'Rajaiya, Jaya']",PLoS One,,,True
80013c44d7d2d3949096511ad6fa424a2c740813,PMC,Influenza A virus-mediated priming enhances cytokine secretion by human dendritic cells infected with Streptococcus pneumoniae,http://dx.doi.org/10.1111/cmi.12122,PMC3798092,23421931,CC BY,"Secondary infections with Streptococcus pneumoniae (SP) are frequently observed following influenza A virus (IAV) infection and have a substantial impact on global health. Despite this, the basis for the disease progression is incompletely understood. To investigate the effect of co-infection on human monocyte-derived dendritic cells (MDDCs) we analysed the expression of clinically important pro-inflammatory and immune-modulatory cytokines. IAV infection or treatment with supernatants from IAV-infected cell cultures resulted in priming of the DCs which subsequently influenced the production of IL-12p70, as well as IL-6, following SP infection. Co-infection of the same cell was not required but this effect was dependent on the time, dose and duration of the infections, as well as pathogen viability, bacterial uptake and endosome acidification. Bacterially infected cells were characterized as the main producers of IL-12p70. Finally, we showed that type I interferons were primarily responsible for the priming of IL-12p70 that was observed by infection with IAV. These results provide a probable mechanism for the elevated levels of particular cytokines observed in IAV and SP co-infected cell cultures with implications for the pathogenic outcome observed during in vivo infection.",2013 Aug 14,"['Kuri, Thomas', 'Smed Sörensen, Anna', 'Thomas, Saskia', 'Karlsson Hedestam, Gunilla B', 'Normark, Staffan', 'Henriques-Normark, Birgitta', 'McInerney, Gerald M', 'Plant, Laura']",Cell Microbiol,,,True
463a646aaf5a4bee77ded050bb89bba468198344,PMC,Influenza A virus-mediated priming enhances cytokine secretion by human dendritic cells infected with Streptococcus pneumoniae,http://dx.doi.org/10.1111/cmi.12122,PMC3798092,23421931,CC BY,"Secondary infections with Streptococcus pneumoniae (SP) are frequently observed following influenza A virus (IAV) infection and have a substantial impact on global health. Despite this, the basis for the disease progression is incompletely understood. To investigate the effect of co-infection on human monocyte-derived dendritic cells (MDDCs) we analysed the expression of clinically important pro-inflammatory and immune-modulatory cytokines. IAV infection or treatment with supernatants from IAV-infected cell cultures resulted in priming of the DCs which subsequently influenced the production of IL-12p70, as well as IL-6, following SP infection. Co-infection of the same cell was not required but this effect was dependent on the time, dose and duration of the infections, as well as pathogen viability, bacterial uptake and endosome acidification. Bacterially infected cells were characterized as the main producers of IL-12p70. Finally, we showed that type I interferons were primarily responsible for the priming of IL-12p70 that was observed by infection with IAV. These results provide a probable mechanism for the elevated levels of particular cytokines observed in IAV and SP co-infected cell cultures with implications for the pathogenic outcome observed during in vivo infection.",2013 Aug 14,"['Kuri, Thomas', 'Smed Sörensen, Anna', 'Thomas, Saskia', 'Karlsson Hedestam, Gunilla B', 'Normark, Staffan', 'Henriques-Normark, Birgitta', 'McInerney, Gerald M', 'Plant, Laura']",Cell Microbiol,,,False
d5535b19156c0be39daefcb8fabb03cbcd43b4b1,PMC,Influenza A virus-mediated priming enhances cytokine secretion by human dendritic cells infected with Streptococcus pneumoniae,http://dx.doi.org/10.1111/cmi.12122,PMC3798092,23421931,CC BY,"Secondary infections with Streptococcus pneumoniae (SP) are frequently observed following influenza A virus (IAV) infection and have a substantial impact on global health. Despite this, the basis for the disease progression is incompletely understood. To investigate the effect of co-infection on human monocyte-derived dendritic cells (MDDCs) we analysed the expression of clinically important pro-inflammatory and immune-modulatory cytokines. IAV infection or treatment with supernatants from IAV-infected cell cultures resulted in priming of the DCs which subsequently influenced the production of IL-12p70, as well as IL-6, following SP infection. Co-infection of the same cell was not required but this effect was dependent on the time, dose and duration of the infections, as well as pathogen viability, bacterial uptake and endosome acidification. Bacterially infected cells were characterized as the main producers of IL-12p70. Finally, we showed that type I interferons were primarily responsible for the priming of IL-12p70 that was observed by infection with IAV. These results provide a probable mechanism for the elevated levels of particular cytokines observed in IAV and SP co-infected cell cultures with implications for the pathogenic outcome observed during in vivo infection.",2013 Aug 14,"['Kuri, Thomas', 'Smed Sörensen, Anna', 'Thomas, Saskia', 'Karlsson Hedestam, Gunilla B', 'Normark, Staffan', 'Henriques-Normark, Birgitta', 'McInerney, Gerald M', 'Plant, Laura']",Cell Microbiol,,,False
85a50734ee9254706c0d4a338a27da6d8e75b0cb,PMC,Influenza A virus-mediated priming enhances cytokine secretion by human dendritic cells infected with Streptococcus pneumoniae,http://dx.doi.org/10.1111/cmi.12122,PMC3798092,23421931,CC BY,"Secondary infections with Streptococcus pneumoniae (SP) are frequently observed following influenza A virus (IAV) infection and have a substantial impact on global health. Despite this, the basis for the disease progression is incompletely understood. To investigate the effect of co-infection on human monocyte-derived dendritic cells (MDDCs) we analysed the expression of clinically important pro-inflammatory and immune-modulatory cytokines. IAV infection or treatment with supernatants from IAV-infected cell cultures resulted in priming of the DCs which subsequently influenced the production of IL-12p70, as well as IL-6, following SP infection. Co-infection of the same cell was not required but this effect was dependent on the time, dose and duration of the infections, as well as pathogen viability, bacterial uptake and endosome acidification. Bacterially infected cells were characterized as the main producers of IL-12p70. Finally, we showed that type I interferons were primarily responsible for the priming of IL-12p70 that was observed by infection with IAV. These results provide a probable mechanism for the elevated levels of particular cytokines observed in IAV and SP co-infected cell cultures with implications for the pathogenic outcome observed during in vivo infection.",2013 Aug 14,"['Kuri, Thomas', 'Smed Sörensen, Anna', 'Thomas, Saskia', 'Karlsson Hedestam, Gunilla B', 'Normark, Staffan', 'Henriques-Normark, Birgitta', 'McInerney, Gerald M', 'Plant, Laura']",Cell Microbiol,,,False
da4856482e2820b8ef50403540207af6b0becde6,PMC,Influenza A virus-mediated priming enhances cytokine secretion by human dendritic cells infected with Streptococcus pneumoniae,http://dx.doi.org/10.1111/cmi.12122,PMC3798092,23421931,CC BY,"Secondary infections with Streptococcus pneumoniae (SP) are frequently observed following influenza A virus (IAV) infection and have a substantial impact on global health. Despite this, the basis for the disease progression is incompletely understood. To investigate the effect of co-infection on human monocyte-derived dendritic cells (MDDCs) we analysed the expression of clinically important pro-inflammatory and immune-modulatory cytokines. IAV infection or treatment with supernatants from IAV-infected cell cultures resulted in priming of the DCs which subsequently influenced the production of IL-12p70, as well as IL-6, following SP infection. Co-infection of the same cell was not required but this effect was dependent on the time, dose and duration of the infections, as well as pathogen viability, bacterial uptake and endosome acidification. Bacterially infected cells were characterized as the main producers of IL-12p70. Finally, we showed that type I interferons were primarily responsible for the priming of IL-12p70 that was observed by infection with IAV. These results provide a probable mechanism for the elevated levels of particular cytokines observed in IAV and SP co-infected cell cultures with implications for the pathogenic outcome observed during in vivo infection.",2013 Aug 14,"['Kuri, Thomas', 'Smed Sörensen, Anna', 'Thomas, Saskia', 'Karlsson Hedestam, Gunilla B', 'Normark, Staffan', 'Henriques-Normark, Birgitta', 'McInerney, Gerald M', 'Plant, Laura']",Cell Microbiol,,,False
bfcb22212525a49970dc301582343e388fc5cfd6,PMC,Gargling for Oral Hygiene and the Development of Fever in Childhood: A Population Study in Japan,http://dx.doi.org/10.2188/jea.JE20100181,PMC3798579,22123226,CC BY,"BACKGROUND: Fever is one of the most common symptoms among children and is usually caused by respiratory infections. Although Japanese health authorities have long recommended gargling to prevent respiratory infections, its effectiveness among children is not clear. METHODS: The children in this observational study were enrolled from 145 nursery schools in Fukuoka City, Japan. Children in the exposure group were instructed to gargle at least once a day. The endpoints of this study were incidence of fever during the daytime and incidence of sickness absence. Differences among gargling agents for each endpoint were also analyzed. RESULTS: A total of 19 595 children aged 2 to 6 years were observed for 20 days (391 900 person-days). In multivariate logistic regression, the overall odds ratio (OR) for fever onset in the gargling group was significantly lower (OR = 0.68). In age-stratified analysis, ORs were significantly lower at age 2 (OR = 0.67), 4 (OR = 0.46), and 5 (OR = 0.41) years. Regarding sickness absence, the overall OR was 0.92 (not significant) in the gargling group. In age-stratified analysis, ORs were significantly lower at age 4 (OR = 0.68), 5 (OR = 0.59), and 6 (OR = 0.63) years. In subgroup analysis, significantly lower ORs for fever onset were observed for children who gargled with green tea (OR = 0.32), functional water (OR = 0.46), or tap water (OR = 0.70). However, the ORs were not significant for sickness absence. CONCLUSIONS: Gargling might be effective in preventing febrile diseases in children.",2012 Jan 5,"['Noda, Tatsuya', 'Ojima, Toshiyuki', 'Hayasaka, Shinya', 'Murata, Chiyoe', 'Hagihara, Akihito']",J Epidemiol,,,True
13d3cd2797da7eb9cc334821680a7b30badafa11,PMC,Interleukin 35: A Key Mediator of Suppression and the Propagation of Infectious Tolerance,http://dx.doi.org/10.3389/fimmu.2013.00315,PMC3798782,24151492,CC BY,"The importance of regulatory T cells (Tregs) in balancing the effector arm of the immune system is well documented, playing a central role in preventing autoimmunity, facilitating graft tolerance following organ transplantation, and having a detrimental impact on the development of anti-tumor immunity. These regulatory responses use a variety of mechanisms to mediate suppression, including soluble factors. While IL-10 and TGF-β are the most commonly studied immunosuppressive cytokines, the recently identified IL-35 has been shown to have potent suppressive function in vitro and in vivo. Furthermore, not only does IL-35 have the ability to directly suppress effector T cell responses, it is also able to expand regulatory responses by propagating infectious tolerance and generating a potent population of IL-35-expressing inducible Tregs. In this review, we summarize research characterizing the structure and function of IL-35, examine its role in disease, and discuss how it can contribute to the induction of a distinct population of inducible Tregs.",2013 Oct 18,"['Olson, Brian M.', 'Sullivan, Jeremy A.', 'Burlingham, William J.']",Front Immunol,,,True
e458fadd59e9f9ac952f6c40f283b14071174259,PMC,Role of Natural Killer and Gamma-Delta T cells in West Nile Virus Infection,http://dx.doi.org/10.3390/v5092298,PMC3798903,24061543,CC BY,"Natural Killer (NK) cells and Gamma-delta T cells are both innate lymphocytes that respond rapidly and non-specifically to viral infection and other pathogens. They are also known to form a unique link between innate and adaptive immunity. Although they have similar immune features and effector functions, accumulating evidence in mice and humans suggest these two cell types have distinct roles in the control of infection by West Nile virus (WNV), a re-emerging pathogen that has caused fatal encephalitis in North America over the past decade. This review will discuss recent studies on these two cell types in protective immunity and viral pathogenesis during WNV infection.",2013 Sep 20,"['Wang, Tian', 'Welte, Thomas']",Viruses,,,True
e466de47aa170d1f457c5fd9e1b01ae0ba0549cc,PMC,"Genetic Analysis of West Nile Virus Isolates from an Outbreak in Idaho, United States, 2006–2007",http://dx.doi.org/10.3390/ijerph10094486,PMC3799518,24065039,CC BY,"West Nile virus (WNV) appeared in the U.S. in 1999 and has since become endemic, with yearly summer epidemics causing tens of thousands of cases of serious disease over the past 14 years. Analysis of WNV strains isolated during the 2006–2007 epidemic seasons demonstrates that a new genetic variant had emerged coincidentally with an intense outbreak in Idaho during 2006. The isolates belonging to the new variant carry a 13 nt deletion, termed ID-Δ13, located at the variable region of the 3′UTR, and are genetically related. The analysis of deletions and insertions in the 3′UTR of two major lineages of WNV revealed the presence of conserved repeats and two indel motifs in the variable region of the 3′UTR. One human and two bird isolates from the Idaho 2006–2007 outbreaks were sequenced using Illumina technology and within-host variability was analyzed. Continued monitoring of new genetic variants is important for public health as WNV continues to evolve.",2013 Sep 23,"['Grinev, Andriyan', 'Chancey, Caren', 'Añez, Germán', 'Ball, Christopher', 'Winkelman, Valerie', 'Williamson, Phillip', 'Foster, Gregory A.', 'Stramer, Susan L.', 'Rios, Maria']",Int J Environ Res Public Health,,,True
31fd4d2067fb03f503ce03d16e323020b9f1d219,PMC,"Genetic Analysis of West Nile Virus Isolates from an Outbreak in Idaho, United States, 2006–2007",http://dx.doi.org/10.3390/ijerph10094486,PMC3799518,24065039,CC BY,"West Nile virus (WNV) appeared in the U.S. in 1999 and has since become endemic, with yearly summer epidemics causing tens of thousands of cases of serious disease over the past 14 years. Analysis of WNV strains isolated during the 2006–2007 epidemic seasons demonstrates that a new genetic variant had emerged coincidentally with an intense outbreak in Idaho during 2006. The isolates belonging to the new variant carry a 13 nt deletion, termed ID-Δ13, located at the variable region of the 3′UTR, and are genetically related. The analysis of deletions and insertions in the 3′UTR of two major lineages of WNV revealed the presence of conserved repeats and two indel motifs in the variable region of the 3′UTR. One human and two bird isolates from the Idaho 2006–2007 outbreaks were sequenced using Illumina technology and within-host variability was analyzed. Continued monitoring of new genetic variants is important for public health as WNV continues to evolve.",2013 Sep 23,"['Grinev, Andriyan', 'Chancey, Caren', 'Añez, Germán', 'Ball, Christopher', 'Winkelman, Valerie', 'Williamson, Phillip', 'Foster, Gregory A.', 'Stramer, Susan L.', 'Rios, Maria']",Int J Environ Res Public Health,,,True
3cf1d3f730cadc87a4392893ee1a6d4da9cb5efb,PMC,The Serological and Virological Investigation of Canine Adenovirus Infection on the Dogs,http://dx.doi.org/10.1155/2013/587024,PMC3800580,24223508,CC BY,"Two types of Canine Adenovirus (CAVs), Canine Adenovirus type 1 (CAV-1), the virus which causes infectious canine hepatitis, and Canine Adenovirus type 2 (CAV-2), which causes canine infectious laryngotracheitis, have been found in dogs. In this study, blood samples taken from 111 dogs, which were admitted to the Internal Medicine Clinic of Selcuk University, Faculty of Veterinary Medicine, with clinical symptoms. Seventy-seven dogs were sampled from Isparta and Burdur dog shelters by random sampling, regardless of the clinical findings. Dogs showed a systemic disease, characterized by fever, diarrhea, vomiting, oculonasal discharge, conjunctivitis, severe moist cough, signs of pulmonary disease and dehydration. Two dogs had corneal opacity and photophobia. In serological studies, 188 serum samples were investigated on the presence of CAV antibodies by ELISA. Total 103 (103/188–54.7%) blood samples were detected to be positive for CAV antibodies by ELISA. However, 85 (85/188–45.2%) blood samples were negative. Blood leukocyte samples from dogs were processed and inoculated onto confluent monolayers of MDCK cells using standard virological techniques. After third passage, cells were examined by direct immunoflourescence test for virus isolation. But positive result was not detected. In conclusion, this study clearly demonstrates the high prevalence of CAV infection in dogs.",2013 Sep 24,"['Bulut, Oya', 'Yapici, Orhan', 'Avci, Oguzhan', 'Simsek, Atilla', 'Atli, Kamil', 'Dik, Irmak', 'Yavru, Sibel', 'Hasircioglu, Sibel', 'Kale, Mehmet', 'Mamak, Nuri']",ScientificWorldJournal,,,True
f86ac2580002e6b374ec325717eeee73e84af1c5,PMC,Steroid-Associated Hip Joint Collapse in Bipedal Emus,http://dx.doi.org/10.1371/journal.pone.0076797,PMC3804596,24204675,CC BY,"In this study we established a bipedal animal model of steroid-associated hip joint collapse in emus for testing potential treatment protocols to be developed for prevention of steroid-associated joint collapse in preclinical settings. Five adult male emus were treated with a steroid-associated osteonecrosis (SAON) induction protocol using combination of pulsed lipopolysaccharide (LPS) and methylprednisolone (MPS). Additional three emus were used as normal control. Post-induction, emu gait was observed, magnetic resonance imaging (MRI) was performed, and blood was collected for routine examination, including testing blood coagulation and lipid metabolism. Emus were sacrificed at week 24 post-induction, bilateral femora were collected for micro-computed tomography (micro-CT) and histological analysis. Asymmetric limping gait and abnormal MRI signals were found in steroid-treated emus. SAON was found in all emus with a joint collapse incidence of 70%. The percentage of neutrophils (Neut %) and parameters on lipid metabolism significantly increased after induction. Micro-CT revealed structure deterioration of subchondral trabecular bone. Histomorphometry showed larger fat cell fraction and size, thinning of subchondral plate and cartilage layer, smaller osteoblast perimeter percentage and less blood vessels distributed at collapsed region in SAON group as compared with the normal controls. Scanning electron microscope (SEM) showed poor mineral matrix and more osteo-lacunae outline in the collapsed region in SAON group. The combination of pulsed LPS and MPS developed in the current study was safe and effective to induce SAON and deterioration of subchondral bone in bipedal emus with subsequent femoral head collapse, a typical clinical feature observed in patients under pulsed steroid treatment. In conclusion, bipedal emus could be used as an effective preclinical experimental model to evaluate potential treatment protocols to be developed for prevention of ON-induced hip joint collapse in patients.",2013 Oct 21,"['Zheng, Li-Zhen', 'Liu, Zhong', 'Lei, Ming', 'Peng, Jiang', 'He, Yi-Xin', 'Xie, Xin-Hui', 'Man, Chi-Wai', 'Huang, Le', 'Wang, Xin-Luan', 'Fong, Daniel Tik-Pui', 'Xiao, De-Ming', 'Wang, Da-Ping', 'Chen, Yang', 'Feng, Jian Q.', 'Liu, Ying', 'Zhang, Ge', 'Qin, Ling']",PLoS One,,,True
5e3a5143a77a6faeb480c65a23137616c14e7bad,PMC,Inhibition of Influenza H7 Hemagglutinin-Mediated Entry,http://dx.doi.org/10.1371/journal.pone.0076363,PMC3806803,24194835,CC BY,"The recent outbreak of H7N9 influenza in China is of high concern to public health. H7 hemagglutinin (HA) plays a critical role in influenza entry and thus HA presents an attractive target for antivirals. Previous studies have suggested that the small molecule tert-butyl hydroquinone (TBHQ) inhibits the entry of influenza H3 HA by binding to the stem loop of HA and stabilizing the neutral pH conformation of HA, thereby disrupting the membrane fusion step. Based on amino acid sequence, structure and immunogenicity, H7 is a related Group 2 HA. In this work we show, using a pseudovirus entry assay, that TBHQ inhibits H7 HA-mediated entry, as well as H3 HA-mediated entry, with an IC50∼6 µM. Using NMR, we show that TBHQ binds to the H7 stem loop region. STD NMR experiments indicate that the aromatic ring of TBHQ makes extensive contact with the H7 HA surface. Limited proteolysis experiments indicate that TBHQ inhibits influenza entry by stabilizing the H7 HA neutral pH conformation. Together, this work suggests that the stem loop region of H7 HA is an attractive target for therapeutic intervention and that TBHQ, which is a widely used food preservative, is a promising lead compound.",2013 Oct 23,"['Antanasijevic, Aleksandar', 'Cheng, Han', 'Wardrop, Duncan J.', 'Rong, Lijun', 'Caffrey, Michael']",PLoS One,,,True
447da2087b2d876e228b40eb8a29446bfd585499,PMC,Co-Infections in Children Hospitalised for Bronchiolitis: Role of Roomsharing,http://dx.doi.org/10.4021/jocmr1556w,PMC3808260,24171054,CC BY,"BACKGROUND: Bronchiolitis is a major cause for hospitalisation in young children during the winter season, with respiratory syncytial virus (RSV) as the main causative virus. Apart from standard hygiene measures, cohorting of RSV-infected patients separately from RSV-negative patients is frequently applied to prevent cross-infection, although evidence to support this practice is lacking. The objective is to evaluate the risk of room sharing between RSV-positive and RSV-negative patients. METHODS: We performed a prospective observational cohort study in children < 2 years hospitalised with acute bronchiolitis. During the first day of admission, patients shared one room, pending results of virological diagnosis (PCR). When diagnostic results were available, RSV-positive and RSV-negative patients were separated. Standard hygienic measures (gowns, gloves, masks, hand washing) were used in all patients. RESULTS: We included 48 patients (83% RSV-positive). Co-infection was found in nine patients at admission, and two during hospitalisation (23%). The two patients with acquired co-infection had been nursed in a single room during the entire admission. None of 37 patients sharing a room with other bronchiolitis patients (20 with patients with a different virus) were co-infected during admission. Disease severity in co-infection was not worse than in mono-infection. CONCLUSION: One in five patients with bronchiolitis was co-infected, but co-infection acquired during admission was rare and was not associated with more severe disease. Room sharing between RSV-positive and RSV-negative patients (on the first day of admission) did not influence the risk of co-infection, suggesting that cohorting of RSV-infected patients separate from non-RSV-infected patients may not be indicated.",2013 Dec 12,"['Bekhof, Jolita', 'Bakker, Joline', 'Reimink, Roelien', 'Wessels, Mirjam', 'Langenhorst, Veerle', 'Brand, Paul L.P.', 'Ruijs, Gijs J.H.M.']",J Clin Med Res,,,True
bda64532f4a16e2885868385170f8bc89ab8f789,PMC,Eukaryotic Initiation Factor 2α - a Downstream Effector of Mammalian Target of Rapamycin - Modulates DNA Repair and Cancer Response to Treatment,http://dx.doi.org/10.1371/journal.pone.0077260,PMC3808413,24204783,CC BY,"In an effort to circumvent resistance to rapamycin – an mTOR inhibitor - we searched for novel rapamycin-downstream-targets that may be key players in the response of cancer cells to therapy. We found that rapamycin, at nM concentrations, increased phosphorylation of eukaryotic initiation factor (eIF) 2α in rapamycin-sensitive and estrogen-dependent MCF-7 cells, but had only a minimal effect on eIF2α phosphorylation in the rapamycin-insensitive triple-negative MDA-MB-231 cells. Addition of salubrinal – an inhibitor of eIF2α dephosphorylation – decreased expression of a surface marker associated with capacity for self renewal, increased senescence and induced clonogenic cell death, suggesting that excessive phosphorylation of eIF2α is detrimental to the cells' survival. Treating cells with salubrinal enhanced radiation-induced increase in eIF2α phosphorylation and clonogenic death and showed that irradiated cells are more sensitive to increased eIF2α phosphorylation than non-irradiated ones. Similar to salubrinal - the phosphomimetic eIF2α variant - S51D - increased sensitivity to radiation, and both abrogated radiation-induced increase in breast cancer type 1 susceptibility gene, thus implicating enhanced phosphorylation of eIF2α in modulation of DNA repair. Indeed, salubrinal inhibited non-homologous end joining as well as homologous recombination repair of double strand breaks that were induced by I-SceI in green fluorescent protein reporter plasmids. In addition to its effect on radiation, salubrinal enhanced eIF2α phosphorylation and clonogenic death in response to the histone deacetylase inhibitor – vorinostat. Finally, the catalytic competitive inhibitor of mTOR - Ku-0063794 - increased phosphorylation of eIF2α demonstrating further the involvement of mTOR activity in modulating eIF2α phosphorylation. These experiments suggest that excessive phosphorylation of eIF2α decreases survival of cancer cells; making eIF2α a worthy target for drug development, with the potential to enhance the cytotoxic effects of established anti-neoplastic therapies and circumvent resistance to rapalogues and possibly to other drugs that inhibit upstream components of the mTOR pathway.",2013 Oct 25,"['Tuval-Kochen, Liron', 'Paglin, Shoshana', 'Keshet, Gilmor', 'Lerenthal, Yaniv', 'Nakar, Charles', 'Golani, Tamar', 'Toren, Amos', 'Yahalom, Joachim', 'Pfeffer, Raphael', 'Lawrence, Yaacov']",PLoS One,,,True
36b5106f87b0cf684bca0e39767d48caedc47d43,PMC,The Role of Mannose-Binding Lectin in Severe Sepsis and Septic Shock,http://dx.doi.org/10.1155/2013/625803,PMC3808714,24223476,CC BY,"Severe sepsis and septic shock are a primary cause of death in patients in intensive care unit (ICU). Investigations upon genetic susceptibility profile to systemic complications during severe infections are a field of increasing scientific interest. Particularly when adaptive immune system is compromised or immature, innate immunity plays a key role in the immediate defense against invasive pathogens. Mannose-binding lectin (MBL) is a serum protein that recognizes a wide range of pathogenic microorganisms and activates complement cascade via the antibody-independent pathway. More than 30% of humans harbor mutations in MBL gene (MBL2) resulting in reduced plasmatic levels and activity. Increased risk of infection acquisition has been largely documented in MBL-deficient patients, but the real impact of this form of innate immunosuppression upon clinical outcome is not clear. In critically ill patients higher incidence and worse prognosis of severe sepsis/septic shock appear to be associated with low-producers haplotypes. However an excess of MBL activation might be also harmful due to the possibility of an unbalanced proinflammatory response and an additional host injury. Strategies of replacement therapies in critically ill patients with severe infections are under investigation but still far to be applied in clinical practice.",2013 Oct 2,"['De Pascale, Gennaro', 'Cutuli, Salvatore Lucio', 'Pennisi, Mariano Alberto', 'Antonelli, Massimo']",Mediators Inflamm,,,True
039ca136c69c998e9a2677259d9de2941a13304a,PMC,Adaptation of novel H7N9 influenza A virus to human receptors,http://dx.doi.org/10.1038/srep03058,PMC3808826,24162312,CC BY,"The emergence of the novel H7N9 influenza A virus (IAV) has caused global concerns about the ability of this virus to spread between humans. Analysis of the receptor-binding properties of this virus using a recombinant protein approach in combination with fetuin-binding, glycan array and human tissue-binding assays demonstrates increased binding of H7 to both α2-6 and α2-8 sialosides as well as reduced binding to α2-3-linked SIAs compared to a closely related avian H7N9 virus from 2008. These differences could be attributed to substitutions Q226L and G186V. Analysis of the enzymatic activity of the neuraminidase N9 protein indicated a reduced sialidase activity, consistent with the reduced binding of H7 to α2-3 sialosides. However, the novel H7N9 virus still preferred binding to α2-3- over α2-6-linked SIAs and was not able to efficiently bind to epithelial cells of human trachea in contrast to seasonal IAV, consistent with its limited human-to-human transmission.",2013 Oct 28,"['Dortmans, J. C. F. M.', 'Dekkers, J.', 'Wickramasinghe, I. N. Ambepitiya', 'Verheije, M. H.', 'Rottier, P. J. M.', 'van Kuppeveld, F. J. M.', 'de Vries, E.', 'de Haan, C. A. M.']",Sci Rep,,,True
d31c808b7108ee70653f288622745ce73ca14adf,PMC,Adaptation of novel H7N9 influenza A virus to human receptors,http://dx.doi.org/10.1038/srep03058,PMC3808826,24162312,CC BY,"The emergence of the novel H7N9 influenza A virus (IAV) has caused global concerns about the ability of this virus to spread between humans. Analysis of the receptor-binding properties of this virus using a recombinant protein approach in combination with fetuin-binding, glycan array and human tissue-binding assays demonstrates increased binding of H7 to both α2-6 and α2-8 sialosides as well as reduced binding to α2-3-linked SIAs compared to a closely related avian H7N9 virus from 2008. These differences could be attributed to substitutions Q226L and G186V. Analysis of the enzymatic activity of the neuraminidase N9 protein indicated a reduced sialidase activity, consistent with the reduced binding of H7 to α2-3 sialosides. However, the novel H7N9 virus still preferred binding to α2-3- over α2-6-linked SIAs and was not able to efficiently bind to epithelial cells of human trachea in contrast to seasonal IAV, consistent with its limited human-to-human transmission.",2013 Oct 28,"['Dortmans, J. C. F. M.', 'Dekkers, J.', 'Wickramasinghe, I. N. Ambepitiya', 'Verheije, M. H.', 'Rottier, P. J. M.', 'van Kuppeveld, F. J. M.', 'de Vries, E.', 'de Haan, C. A. M.']",Sci Rep,,,True
c57fb53010f62a669421b0f4894a26e22e0e496c,PMC,GenomeFingerprinter: The Genome Fingerprint and the Universal Genome Fingerprint Analysis for Systematic Comparative Genomics,http://dx.doi.org/10.1371/journal.pone.0077912,PMC3812135,24205026,CC BY,"BACKGROUND: No attention has been paid on comparing a set of genome sequences crossing genetic components and biological categories with far divergence over large size range. We define it as the systematic comparative genomics and aim to develop the methodology. RESULTS: First, we create a method, GenomeFingerprinter, to unambiguously produce a set of three-dimensional coordinates from a sequence, followed by one three-dimensional plot and six two-dimensional trajectory projections, to illustrate the genome fingerprint of a given genome sequence. Second, we develop a set of concepts and tools, and thereby establish a method called the universal genome fingerprint analysis (UGFA). Particularly, we define the total genetic component configuration (TGCC) (including chromosome, plasmid, and phage) for describing a strain as a systematic unit, the universal genome fingerprint map (UGFM) of TGCC for differentiating strains as a universal system, and the systematic comparative genomics (SCG) for comparing a set of genomes crossing genetic components and biological categories. Third, we construct a method of quantitative analysis to compare two genomes by using the outcome dataset of genome fingerprint analysis. Specifically, we define the geometric center and its geometric mean for a given genome fingerprint map, followed by the Euclidean distance, the differentiate rate, and the weighted differentiate rate to quantitatively describe the difference between two genomes of comparison. Moreover, we demonstrate the applications through case studies on various genome sequences, giving tremendous insights into the critical issues in microbial genomics and taxonomy. CONCLUSIONS: We have created a method, GenomeFingerprinter, for rapidly computing, geometrically visualizing, intuitively comparing a set of genomes at genome fingerprint level, and hence established a method called the universal genome fingerprint analysis, as well as developed a method of quantitative analysis of the outcome dataset. These have set up the methodology of systematic comparative genomics based on the genome fingerprint analysis.",2013 Oct 29,"['Ai, Yuncan', 'Ai, Hannan', 'Meng, Fanmei', 'Zhao, Lei']",PLoS One,,,True
1dad67bd586092707fb9e7d311d465b82b85425f,PMC,Infectious Bronchitis Virus Generates Spherules from Zippered Endoplasmic Reticulum Membranes,http://dx.doi.org/10.1128/mBio.00801-13,PMC3812713,24149513,CC BY,"Replication of positive-sense RNA viruses is associated with the rearrangement of cellular membranes. Previous work on the infection of tissue culture cell lines with the betacoronaviruses mouse hepatitis virus and severe acute respiratory syndrome coronavirus (SARS-CoV) showed that they generate double-membrane vesicles (DMVs) and convoluted membranes as part of a reticular membrane network. Here we describe a detailed study of the membrane rearrangements induced by the avian gammacoronavirus infectious bronchitis virus (IBV) in a mammalian cell line but also in primary avian cells and in epithelial cells of ex vivo tracheal organ cultures. In all cell types, structures novel to IBV infection were identified that we have termed zippered endoplasmic reticulum (ER) and spherules. Zippered ER lacked luminal space, suggesting zippering of ER cisternae, while spherules appeared as uniform invaginations of zippered ER. Electron tomography showed that IBV-induced spherules are tethered to the zippered ER and that there is a channel connecting the interior of the spherule with the cytoplasm, a feature thought to be necessary for sites of RNA synthesis but not seen previously for membrane rearrangements induced by coronaviruses. We also identified DMVs in IBV-infected cells that were observed as single individual DMVs or were connected to the ER via their outer membrane but not to the zippered ER. Interestingly, IBV-induced spherules strongly resemble confirmed sites of RNA synthesis for alphaviruses, nodaviruses, and bromoviruses, which may indicate similar strategies of IBV and these diverse viruses for the assembly of RNA replication complexes. IMPORTANCE All positive-sense single-stranded RNA viruses induce rearranged cellular membranes, providing a platform for viral replication complex assembly and protecting viral RNA from cellular defenses. We have studied the membrane rearrangements induced by an important poultry pathogen, the gammacoronavirus infectious bronchitis virus (IBV). Previous work studying closely related betacoronaviruses identified double-membrane vesicles (DMVs) and convoluted membranes (CMs) derived from the endoplasmic reticulum (ER) in infected cells. However, the role of DMVs and CMs in viral RNA synthesis remains unclear because these sealed vesicles lack a means of delivering viral RNA to the cytoplasm. Here, we characterized structures novel to IBV infection: zippered ER and small vesicles tethered to the zippered ER termed spherules. Significantly, spherules contain a channel connecting their interior to the cytoplasm and strongly resemble confirmed sites of RNA synthesis for other positive-sense RNA viruses, making them ideal candidates for the site of IBV RNA synthesis.",2013 Oct 22,"['Maier, Helena J.', 'Hawes, Philippa C.', 'Cottam, Eleanor M.', 'Mantell, Judith', 'Verkade, Paul', 'Monaghan, Paul', 'Wileman, Tom', 'Britton, Paul']",mBio,,,True
bdfce208ef62424bc68fdb610364dab6416365e1,PMC,Physiological Level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle,http://dx.doi.org/10.1371/journal.pone.0078119,PMC3813428,24205120,CC BY,"Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM) and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ) in the pre-B cell receptor (pre-BCR) complex, we partially replaced (bovinized) the hIgM constant domain with the counterpart of bovine IgM (bIgM) that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO), the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype) in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG) can be produced from such Tc cattle.",2013 Oct 24,"['Sano, Akiko', 'Matsushita, Hiroaki', 'Wu, Hua', 'Jiao, Jin-An', 'Kasinathan, Poothappillai', 'Sullivan, Eddie J.', 'Wang, Zhongde', 'Kuroiwa, Yoshimi']",PLoS One,,,True
b59f1ed9272403216c276badc217b78b39251098,PMC,Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity,http://dx.doi.org/10.1371/journal.ppat.1003703,PMC3814336,24204261,CC BY,"The innate immune response to viruses is initiated when specialized cellular sensors recognize viral danger signals. Here we show that truncated forms of viral genomes that accumulate in infected cells potently trigger the sustained activation of the transcription factors IRF3 and NF-κB and the production type I IFNs through a mechanism independent of IFN signaling. We demonstrate that these defective viral genomes (DVGs) are generated naturally during respiratory infections in vivo even in mice lacking the type I IFN receptor, and their appearance coincides with the production of cytokines during infections with Sendai virus (SeV) or influenza virus. Remarkably, the hallmark antiviral cytokine IFNβ is only expressed in lung epithelial cells containing DVGs, while cells within the lung that contain standard viral genomes alone do not express this cytokine. Together, our data indicate that DVGs generated during viral replication are a primary source of danger signals for the initiation of the host immune response to infection.",2013 Oct 31,"['Tapia, Karla', 'Kim, Won-keun', 'Sun, Yan', 'Mercado-López, Xiomara', 'Dunay, Emily', 'Wise, Megan', 'Adu, Michael', 'López, Carolina B.']",PLoS Pathog,,,True
63dda1b262c68b84a8058a50480f0d5ae1b4f2ae,PMC,Identification of Novel Compounds Inhibiting Chikungunya Virus-Induced Cell Death by High Throughput Screening of a Kinase Inhibitor Library,http://dx.doi.org/10.1371/journal.pntd.0002471,PMC3814572,24205414,CC BY,"Chikungunya virus (CHIKV) is a mosquito-borne arthrogenic alphavirus that causes acute febrile illness in humans accompanied by joint pains and in many cases, persistent arthralgia lasting weeks to years. The re-emergence of CHIKV has resulted in numerous outbreaks in the eastern hemisphere, and threatens to expand in the foreseeable future. Unfortunately, no effective treatment is currently available. The present study reports the use of resazurin in a cell-based high-throughput assay, and an image-based high-content assay to identify and characterize inhibitors of CHIKV-infection in vitro. CHIKV is a highly cytopathic virus that rapidly kills infected cells. Thus, cell viability of HuH-7 cells infected with CHIKV in the presence of compounds was determined by measuring metabolic reduction of resazurin to identify inhibitors of CHIKV-associated cell death. A kinase inhibitor library of 4,000 compounds was screened against CHIKV infection of HuH-7 cells using the resazurin reduction assay, and the cell toxicity was also measured in non-infected cells. Seventy-two compounds showing ≥50% inhibition property against CHIKV at 10 µM were selected as primary hits. Four compounds having a benzofuran core scaffold (CND0335, CND0364, CND0366 and CND0415), one pyrrolopyridine (CND0545) and one thiazol-carboxamide (CND3514) inhibited CHIKV-associated cell death in a dose-dependent manner, with EC(50) values between 2.2 µM and 7.1 µM. Based on image analysis, these 6 hit compounds did not inhibit CHIKV replication in the host cell. However, CHIKV-infected cells manifested less prominent apoptotic blebs typical of CHIKV cytopathic effect compared with the control infection. Moreover, treatment with these compounds reduced viral titers in the medium of CHIKV-infected cells by up to 100-fold. In conclusion, this cell-based high-throughput screening assay using resazurin, combined with the image-based high content assay approach identified compounds against CHIKV having a novel antiviral activity - inhibition of virus-induced CPE - likely by targeting kinases involved in apoptosis.",2013 Oct 31,"['Cruz, Deu John M.', 'Bonotto, Rafaela M.', 'Gomes, Rafael G. B.', 'da Silva, Camila T.', 'Taniguchi, Juliana B.', 'No, Joo Hwan', 'Lombardot, Benoit', 'Schwartz, Olivier', 'Hansen, Michael A. E.', 'Freitas-Junior, Lucio H.']",PLoS Negl Trop Dis,,,True
d3a753e3847b2c8524486ee213fb614c3c52d8c3,PMC,Diagnosis of West Nile Virus Human Infections: Overview and Proposal of Diagnostic Protocols Considering the Results of External Quality Assessment Studies,http://dx.doi.org/10.3390/v5102329,PMC3814591,24072061,CC BY,"West Nile virus, genus Flavivirus, is transmitted between birds and occasionally other animals by ornithophilic mosquitoes. This virus also infects humans causing asymptomatic infections in about 85% of cases and <1% of clinical cases progress to severe neuroinvasive disease. The virus also presents a threat since most infections remain unapparent. However, the virus contained in blood and organs from asymptomatically infected donors can be transmitted to recipients of these infectious tissues. This paper reviews the presently available methods to achieve the laboratory diagnosis of West Nile virus infections in humans, discussing the most prominent advantages and disadvantages of each in light of the results obtained during four different External Quality Assessment studies carried out by the European Network for ‘Imported’ Viral Diseases (ENIVD).",2013 Sep 25,"['Sambri, Vittorio', 'Capobianchi, Maria R.', 'Cavrini, Francesca', 'Charrel, Rémi', 'Donoso-Mantke, Olivier', 'Escadafal, Camille', 'Franco, Leticia', 'Gaibani, Paolo', 'Gould, Ernest A.', 'Niedrig, Matthias', 'Papa, Anna', 'Pierro, Anna', 'Rossini, Giada', 'Sanchini, Andrea', 'Tenorio, Antonio', 'Varani, Stefania', 'Vázquez, Ana', 'Vocale, Caterina', 'Zeller, Herve']",Viruses,,,True
7a0108c70d3af86c64911d951b82ec9b1bda2818,PMC,"Sequence Heterogeneity of the ORF3 Gene of Porcine Epidemic Diarrhea Viruses Field Samples in Fujian, China, 2010–2012",http://dx.doi.org/10.3390/v5102375,PMC3814593,24084234,CC BY,"Twenty-seven field samples that showed positive in PEDV detection were collected from different farms of Fujian province from 2010 to 2012. Their heterogeneity was investigated by analysis of the ORF3 gene because of its potential function as a representation of virulence. According to the results, six Fujian strains in Group 1 showed a different genotype with unique point mutations, which might be used in differentiation between PEDV groups and brought potential antigenic variation. P55 and five reference strains in Group 2 had a long length deletion, showing another genotype and might be involved in the variation of virulence. Phylogenetic analysis revealed that the collected Fujian strains were very distant from the vaccine development strain CV777, which might be the reason why the vaccine was inefficient to control the disease. The results can help to reconsider the strategy of PEDV vaccine management and prevent outbreaks of PEDV-induced diarrhea more efficiently.",2013 Sep 30,"['Chen, Xi', 'Zeng, Lili', 'Yang, Jinxian', 'Yu, Fusong', 'Ge, Junqing', 'Guo, Qing', 'Gao, Xindang', 'Song, Tieying']",Viruses,,,True
78c991a34ec87c73006a683cd641762d15597890,PMC,Detection and Molecular Diversity of Spike Gene of Porcine Epidemic Diarrhea Virus in China,http://dx.doi.org/10.3390/v5102601,PMC3814607,24153062,CC BY,"Since late 2010, porcine epidemic diarrhea virus (PEDV) has rapidly disseminated all over the China and caused considerable morbidity and high mortality (up to 100%) in neonatal piglets. 79.66% (141 of 177) pig farms in 29 provinces (excluding Tibet and Hainan, China) and 72.27% (417 of 577) samples were positive for PEDV confirmed by reverse transcription-polymerase chain reaction (RT-PCR). The full-length S genes of representative field strains were sequenced. 33 field strains share 93.5%–99.9% homologies with each other at the nucleotide sequence level and 92.3%–99.8% homologies with each other at the amino acids sequence level. Most field strains have nucleotide deletion and insertion regions, and show lower homologies (93.5%–94.2%) with Chinese classical strain CH/S, however higher homologies (97.1%–99.3%) with recent strain CHGD-1. The phylogenetic analysis showed there are classical strains and variants prevailing in pig herd in China. PEDV has a high detection rate in pig herds in China. Sequence analysis indicated the S genes of recent field strains have heterogeneity and the variants are predominant.",2013 Oct 22,"['Chen, Jianfei', 'Liu, Xiaozhen', 'Shi, Da', 'Shi, Hongyan', 'Zhang, Xin', 'Li, Changlong', 'Chi, Yanbin', 'Feng, Li']",Viruses,,,True
937c21d92c53102251dc79fb436701d149789d4d,PMC,Bats and Viruses: Friend or Foe?,http://dx.doi.org/10.1371/journal.ppat.1003651,PMC3814676,24204253,CC BY,,2013 Oct 31,"['Wynne, James W.', 'Wang, Lin-Fa']",PLoS Pathog,,,True
25742d7fc7e3a5dfd8af95c2dbc9731494d13e67,PMC,The use of oral recombinant feline interferon omega in two cats with type II diabetes mellitus and concurrent feline chronic gingivostomatitis syndrome,http://dx.doi.org/10.1186/2046-0481-66-19,PMC3816157,24153100,CC BY,"Feline Chronic Gingivostomatitis Syndrome (FCGS) is a common disease in clinical practice. Among the therapeutic options available, long-acting corticosteroids are frequently used due to their anti-inflammatory and immunosuppressive properties. Although they may improve the clinical symptoms, they can lead to a progressive form of the disease that becomes refractory to treatment. Furthermore, their direct relationship with type II diabetes mellitus (DM) is well known. Consequently, these drugs are controversial and not recommended for routine management of FCGS. Recombinant feline interferon-omega (rFeIFN-ω) is an immunomodulatory compound. Recently, its daily oral administration has been shown to be successful in treating refractory cases of FCGS. This case study describes two clinical cases of type II DM complicated by FCGS. Both animals were calicivirus positive and they had been previously treated with long-acting corticosteroids, which may have been the major cause of DM. The two cats were treated with glargine insulin (Lantus, starting dose 1 IU/cat twice daily (BID)), achieving remission 10 and 18 weeks later respectively. Considering the difficulty with control of FCGS in these animals, an oral daily dose of rFeIFN-ω was started as an alternative to long-acting corticosteroids. In both cats oral clinical signs gradually improved and 60 days after the start of therapy the owners reported a significant relief of pain during mastication. According to the authors’ knowledge, this is the first case report that describes the successful use of rFeIFN-ω in the management of FCGS in type II diabetic cats, in which long-acting corticosteroids are contraindicated.",2013 Oct 23,"['Leal, Rodolfo O', 'Gil, Solange', 'Brito, Maria TV', 'McGahie, David', 'Niza, Maria MRE', 'Tavares, Luís']",Ir Vet J,,,True
6460342e18e6d3fea8f62630e12b083d46a6eb99,PMC,EpiBasket: how e-commerce tools can improve epidemiological preparedness,http://dx.doi.org/10.3402/ehtj.v6i0.19748,PMC3816197,24183326,CC BY,"BACKGROUND: Should an emerging infectious disease outbreak or an environmental disaster occur, the collection of epidemiological data must start as soon as possible after the event's onset. Questionnaires are usually built de novo for each event, resulting in substantially delayed epidemiological responses that are detrimental to the understanding and control of the event considered. Moreover, the public health and/or academic institution databases constructed with responses to different questionnaires are usually difficult to merge, impairing necessary collaborations. We aimed to show that e-commerce concepts and software tools can be readily adapted to enable rapid collection of data after an infectious disease outbreak or environmental disaster. Here, the ‘customers’ are the epidemiologists, who fill their shopping ‘baskets’ with standardised questions. METHODS: For each epidemiological field, a catalogue of questions is constituted by identifying the relevant variables based on a review of the published literature on similar circumstances. Each question is tagged with information on its source papers. Epidemiologists can then tailor their own questionnaires by choosing appropriate questions from this catalogue. The software immediately provides them with ready-to-use forms and online questionnaires. All databases constituted by the different EpiBasket users are interoperable, because the corresponding questionnaires are derived from the same corpus of questions. RESULTS: A proof-of-concept prototype was developed for Knowledge, Attitudes and Practice (KAP) surveys, which is one of the fields of the epidemiological investigation frequently explored during, or after, an outbreak or environmental disaster. The catalogue of questions was initiated from a review of the KAP studies conducted during or after the 2003 severe acute respiratory syndrome epidemic. CONCLUSION: Rapid collection of standardised data after an outbreak or environmental disaster can be facilitated by transposing the e-commerce paradigm to epidemiology, taking advantage of the powerful software tools already available.",2013 Oct 31,"['Xing, Weijia', 'Hejblum, Gilles', 'Valleron, Alain-Jacques']",Emerg Health Threats J,,,True
0a11a6e99c61da77f540fa28b3ab843761537711,PMC,RNAi Therapeutic Platforms for Lung Diseases,http://dx.doi.org/10.3390/ph6020223,PMC3816685,24275949,CC BY,"RNA interference (RNAi) is rapidly becoming an important method for analyzing gene functions in many eukaryotes and holds promise for the development of therapeutic gene silencing. The induction of RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA) degradation. Two types of small RNA molecules, i.e. small interfering RNAs (siRNAs) and microRNAs (miRNAs), are central to RNAi. Drug discovery studies and novel treatments of siRNAs are currently targeting a wide range of diseases, including various viral infections and cancers. Lung diseases in general are attractive targets for siRNA therapeutics because of their lethality and prevalence. In addition, the lung is anatomically accessible to therapeutic agents via the intrapulmonary route. Recently, increasing evidence indicates that miRNAs play an important role in lung abnormalities, such as inflammation and oncogenesis. Therefore, miRNAs are being targeted for therapeutic purposes. In this review, we present strategies for RNAi delivery and discuss the current state-of-the-art RNAi-based therapeutics for various lung diseases.",2013 Feb 6,"['Fujita, Yu', 'Takeshita, Fumitaka', 'Kuwano, Kazuyoshi', 'Ochiya, Takahiro']",Pharmaceuticals (Basel),,,True
ebf258ca8bfc0adbd09d0ebe0c5f25688fbc7c34,PMC,Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Epithelial Cells Are Less Tolerant to Infection by Staphylococcus aureus,http://dx.doi.org/10.1371/journal.pone.0079566,PMC3817128,24223971,CC BY,"Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway and provides reducing energy to all cells by maintaining redox balance. The most common clinical manifestations in patients with G6PD deficiency are neonatal jaundice and acute hemolytic anemia. The effects of microbial infection in patients with G6PD deficiency primarily relate to the hemolytic anemia caused by Plasmodium or viral infections and the subsequent medication that is required. We are interested in studying the impact of bacterial infection in G6PD-deficient cells. G6PD knock down A549 lung carcinoma cells, together with the common pathogen Staphylococcus aureus, were employed in our cell infection model. Here, we demonstrate that a lower cell viability was observed among G6PD-deficient cells when compared to scramble controls upon bacterial infection using the MTT assay. A significant increase in the intracellular ROS was detected among S. aureus-infected G6PD-deficient cells by observing dichlorofluorescein (DCF) intensity within cells under a fluorescence microscope and quantifying this signal using flow cytometry. The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. A higher expression level of the intrinsic apoptotic initiator caspase-9, as well as the downstream effector caspase-3, was detected by Western blotting analysis of G6PD-deficient cells following bacterial infection. In conclusion, we propose that bacterial infection, perhaps the secreted S. aureus α-hemolysin in this case, promotes the accumulation of intracellular ROS in G6PD-deficient cells. This would trigger a stronger apoptotic activity through the intrinsic pathway thereby reducing cell viability when compared to wild type cells.",2013 Nov 4,"['Hsieh, Yi-Ting', 'Lin, Mei-Hui', 'Ho, Hung-Yao', 'Chen, Lei-Chin', 'Chen, Chien-Cheng', 'Shu, Jwu-Ching']",PLoS One,,,True
2d266d6c9ef81ffefa8fc5ba319851d220e71cbd,PMC,Autologous Antibody Capture to Enrich Immunogenic Viruses for Viral Discovery,http://dx.doi.org/10.1371/journal.pone.0078454,PMC3817278,24223808,CC BY,"Discovery of new viruses has been boosted by novel deep sequencing technologies. Currently, many viruses can be identified by sequencing without knowledge of the pathogenicity of the virus. However, attributing the presence of a virus in patient material to a disease in the patient can be a challenge. One approach to meet this challenge is identification of viral sequences based on enrichment by autologous patient antibody capture. This method facilitates identification of viruses that have provoked an immune response within the patient and may increase the sensitivity of the current virus discovery techniques. To demonstrate the utility of this method, virus discovery deep sequencing (VIDISCA-454) was performed on clinical samples from 19 patients: 13 with a known respiratory viral infection and 6 with a known gastrointestinal viral infection. Patient sera was collected from one to several months after the acute infection phase. Input and antibody capture material was sequenced and enrichment was assessed. In 18 of the 19 patients, viral reads from immunogenic viruses were enriched by antibody capture (ranging between 1.5x to 343x in respiratory material, and 1.4x to 53x in stool). Enriched reads were also determined in an identity independent manner by using a novel algorithm Xcompare. In 16 of the 19 patients, 21% to 100% of the enriched reads were derived from infecting viruses. In conclusion, the technique provides a novel approach to specifically identify immunogenic viral sequences among the bulk of sequences which are usually encountered during virus discovery metagenomics.",2013 Nov 4,"['Oude Munnink, Bas B.', 'Jazaeri Farsani, Seyed Mohammad', 'Deijs, Martin', 'Jonkers, Jiri', 'Verhoeven, Joost T. P.', 'Ieven, Margareta', 'Goossens, Herman', 'de Jong, Menno D.', 'Berkhout, Ben', 'Loens, Katherine', 'Kellam, Paul', 'Bakker, Margreet', 'Canuti, Marta', 'Cotten, Matthew', 'van der Hoek, Lia']",PLoS One,,,True
cf0d47062feee58725fffdbd8b91eec680237fc1,PMC,Targeting Antigens to Dendritic Cell Receptors for Vaccine Development,http://dx.doi.org/10.1155/2013/869718,PMC3817681,24228179,CC BY,"Dendritic cells (DCs) are highly specialized antigen presenting cells of the immune system which play a key role in regulating immune responses. Depending on the method of antigen delivery, DCs stimulate immune responses or induce tolerance. As a consequence of the dual function of DCs, DCs are studied in the context of immunotherapy for both cancer and autoimmune diseases. In vaccine development, a major aim is to induce strong, specific T-cell responses. This is achieved by targeting antigen to cell surface molecules on DCs that efficiently channel the antigen into endocytic compartments for loading onto MHC molecules and stimulation of T-cell responses. The most attractive cell surface receptors, expressed on DCs used as targets for antigen delivery for cancer and other diseases, are discussed.",2013 Oct 8,"['Apostolopoulos, Vasso', 'Thalhammer, Theresia', 'Tzakos, Andreas G.', 'Stojanovska, Lily']",J Drug Deliv,,,True
b5215808485ffba5aa16d95577bd6344ede9d45c,PMC,Viral IRES Prediction System - a Web Server for Prediction of the IRES Secondary Structure In Silico,http://dx.doi.org/10.1371/journal.pone.0079288,PMC3818432,24223923,CC BY,"The internal ribosomal entry site (IRES) functions as cap-independent translation initiation sites in eukaryotic cells. IRES elements have been applied as useful tools for bi-cistronic expression vectors. Current RNA structure prediction programs are unable to predict precisely the potential IRES element. We have designed a viral IRES prediction system (VIPS) to perform the IRES secondary structure prediction. In order to obtain better results for the IRES prediction, the VIPS can evaluate and predict for all four different groups of IRESs with a higher accuracy. RNA secondary structure prediction, comparison, and pseudoknot prediction programs were implemented to form the three-stage procedure for the VIPS. The backbone of VIPS includes: the RNAL fold program, aimed to predict local RNA secondary structures by minimum free energy method; the RNA Align program, intended to compare predicted structures; and pknotsRG program, used to calculate the pseudoknot structure. VIPS was evaluated by using UTR database, IRES database and Virus database, and the accuracy rate of VIPS was assessed as 98.53%, 90.80%, 82.36% and 80.41% for IRES groups 1, 2, 3, and 4, respectively. This advance useful search approach for IRES structures will facilitate IRES related studies. The VIPS on-line website service is available at http://140.135.61.250/vips/.",2013 Nov 5,"['Hong, Jun-Jie', 'Wu, Tzong-Yuan', 'Chang, Tsair-Yuan', 'Chen, Chung-Yung']",PLoS One,,,True
bc381e908d987cbecf5fb3df2640a7c878886405,PMC,Broad-Spectrum Detection of H5 Subtype Influenza A Viruses with a New Fluorescent Immunochromatography System,http://dx.doi.org/10.1371/journal.pone.0076753,PMC3819354,24223117,CC BY,"Immunochromatography (IC) is an antigen-detection assay that plays an important role in the rapid diagnosis of influenza virus because the protocol is short time and easy to use. Despite the usability of IC, the sensitivity is approximately 10(3) pfu per reaction. In addition, antigen-antibody interaction-based method cannot be used for the detection of influenza viruses with major antigenic change. In this study, we established the use of fluorescent immunochromatography (FLIC) to detect a broad spectrum of H5 subtype influenza A viruses. This method has improved sensitivity 10–100 fold higher than traditional IC because of the use of fluorescent conjugated beads. Our Type-E FLIC kit detected all of the H5 subtype influenza viruses that were examined, as well as recombinant hemagglutinin (HA) proteins (rHAs) belonging to the Eurasian H5 subtype viruses and the Type-N diagnosed North American H5 subtype influenza A viruses. Thus, this kit has the improved potential to detect H5 subtype influenza viruses of different clades with both Type-E and Type-N FLIC kits. Compared with PCR-based diagnosis, FLIC has a strong advantage in usability, because the sample preparation required for FLIC is only mix-and-drop without any additional steps such as RNA extraction. Our results can provide new strategies against the spread and transmission of HPAI H5N1 viruses in birds and mammals including humans.",2013 Nov 6,"['Sakurai, Akira', 'Takayama, Katsuyoshi', 'Nomura, Namiko', 'Munakata, Tsubasa', 'Yamamoto, Naoki', 'Tamura, Tsuruki', 'Yamada, Jitsuho', 'Hashimoto, Masako', 'Kuwahara, Kazuhiko', 'Sakoda, Yoshihiro', 'Suda, Yoshihiko', 'Kobayashi, Yukuharu', 'Sakaguchi, Nobuo', 'Kida, Hiroshi', 'Kohara, Michinori', 'Shibasaki, Futoshi']",PLoS One,,,True
1829dd66176c20fb22a9d7186d62fa596cc93f9c,PMC,Rhinovirus-Induced Exacerbations of Asthma and COPD,http://dx.doi.org/10.1155/2013/405876,PMC3820304,24278777,CC BY,"Over the past two decades, increasing evidence has shown that, in patients with chronic airways disease, viral infection is the most common cause of exacerbation. This review will examine the evidence for viral-induced exacerbations of asthma and chronic obstructive lung disease and the potential mechanisms by which viruses cause exacerbations. Attention will be focused on rhinovirus, the most common cause of respiratory exacerbations. Exacerbations due to rhinovirus, which infects relatively few cells in the airway and does not cause the cytotoxicity of other viruses such as influenza or respiratory syncytial virus, are particularly poorly understood. While the innate immune response likely plays a role in rhinovirus-induced exacerbations, its precise role, either adaptive or maladaptive, is debated. Because current treatment strategies are only partially effective, further research examining the cellular and molecular mechanisms underlying viral-induced exacerbations of chronic airways diseases is warranted.",2013 Feb 21,"Hershenson, Marc B.",Scientifica (Cairo),,,True
25eb6cba256ef7c1dce823fc897b29a642aa0d5c,PMC,"The Past, Present, and Future of Public Health Surveillance",http://dx.doi.org/10.6064/2012/875253,PMC3820481,24278752,CC BY,"This paper provides a review of the past, present, and future of public health surveillance—the ongoing systematic collection, analysis, interpretation, and dissemination of health data for the planning, implementation, and evaluation of public health action. Public health surveillance dates back to the first recorded epidemic in 3180 B.C. in Egypt. Hippocrates (460 B.C.–370 B.C.) coined the terms endemic and epidemic, John Graunt (1620–1674) introduced systematic data analysis, Samuel Pepys (1633–1703) started epidemic field investigation, William Farr (1807–1883) founded the modern concept of surveillance, John Snow (1813–1858) linked data to intervention, and Alexander Langmuir (1910–1993) gave the first comprehensive definition of surveillance. Current theories, principles, and practice of public health surveillance are summarized. A number of surveillance dichotomies, such as epidemiologic surveillance versus public health surveillance, are described. Some future scenarios are presented, while current activities that can affect the future are summarized: exploring new frontiers; enhancing computer technology; improving epidemic investigations; improving data collection, analysis, dissemination, and use; building on lessons from the past; building capacity; enhancing global surveillance. It is concluded that learning from the past, reflecting on the present, and planning for the future can further enhance public health surveillance.",2012 Aug 5,"Choi, Bernard C. K.",Scientifica (Cairo),,,True
27969ab6c34a3d9b630666d5876256a9641bc05a,PMC,How Do Viruses Avoid Inhibition by Endogenous Cellular MicroRNAs?,http://dx.doi.org/10.1371/journal.ppat.1003694,PMC3820716,24244153,CC BY,,2013 Nov 7,"Cullen, Bryan R.",PLoS Pathog,,,True
c8973a511fb65247ed8f08c777512f17d5c4e977,PMC,Serum proteomics analysis and comparisons using iTRAQ in the progression of hepatitis B,http://dx.doi.org/10.3892/etm.2013.1310,PMC3820766,24223640,CC BY,"The aim of this study was to analyze the changes in serum protein levels in the progression of hepatitis B using isobaric tags for relative and absolute quantitation (iTRAQ) analysis, in addition to comparing the serum protein levels of patients with chronic hepatitis B (CHB), patients with hepatitis B virus-induced acute-on-chronic liver failure (HBV-induced ACLF) and normal individuals. Protein analysis was performed on 15 serum samples using iTRAQ. The study population included healthy controls (n=5), patients with CHB (n=5) and patients with HBV-induced ACLF (n=5). Western blotting was used to verify the results in an additional nine serum samples from healthy controls, patients with CHB and patients with HBV-induced ACLF (n=3, respectively). Using iTRAQ analysis, 16 different serum proteins with ≥1.5-fold differences in expression levels were identified in the patients with CHB and ACLF compared with the healthy controls. Five of those proteins, C-reactive protein precursor, hemoglobin β chain variant Hb S-Wake, apolipoprotein J precursor, platelet factor 4 precursor and vitronectin, which demonstrated the greatest differences in their expression levels and the most significant correlation with liver diseases, were subsequently verified using western blotting. The western blotting results were consistent with the results from the iTRAQ. Two of the five proteins are not classified by biological process, and the biological functions of all the proteins in HBV-induced ACLF remain unclear. This preliminary study demonstrated that a correlation between the expression of various serum proteins and the different pathogenetic conditions induced by HBV may exist. The analysis of a larger number of samples is required to identify potential protein biomarkers that may be involved in the pathogenesis and progression of hepatitis B.",2013 Nov 18,"['PENG, LIANG', 'LIU, JING', 'LI, YANG-MEI', 'HUANG, ZHAN-LIAN', 'WANG, PEI-PEI', 'GU, YU-RONG', 'ZHENG, YU-BAO', 'GAO, ZHI-LIANG']",Exp Ther Med,,,True
17a425d3e66241ada9c347aa0e0387231be31dcd,PMC,"Yu Ping Feng San, an Ancient Chinese Herbal Decoction Containing Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, Regulates the Release of Cytokines in Murine Macrophages",http://dx.doi.org/10.1371/journal.pone.0078622,PMC3823765,24244327,CC BY,"Yu Ping Feng San (YPFS), a Chinese herbal decoction, is composed of Astragali Radix (AR; Huangqi), Atractylodis Macrocephalae Rhizoma (AMR; Baizhu) and Saposhnikoviae Radix (SR; Fangfeng) in a weight ratio of 1∶2∶1. Clinically, YPFS has been widely used to regulate immune functions; however, the action mechanism of it is not known. Here, we addressed this issue by providing detail analyses of chemical and biological properties of YPFS. By using rapid resolution liquid chromatography coupled with mass spectrometry, fifteen chemicals deriving from different herbs of YPFS were determined, and which served as a control for the standardization of the herbal extract of YPFS. In general, the amounts of chosen chemical markers were higher in a preparation of YPFS as compared to that of single herb or two-herb compositions. In order to reveal the immune functions of YPFS, the standardized extract was applied onto cultured murine macrophages. The treatment of YPFS stimulated the mRNA and protein expressions of pro-inflammatory cytokines via activation of NF-κB by enhancing IκBα degradation. In contrast, the application of YPFS suppressed the expressions of pro-inflammatory cytokines significantly in the lipopolysaccharide (LPS)-induced chronic inflammation model. In addition, YPFS could up regulate the phagocytic activity in cultured macrophages. These results therefore supported the bi-directional immune-modulatory roles of YPFS in regulating the releases of cytokines from macrophages.",2013 Nov 11,"['Du, Crystal Y. Q.', 'Choi, Roy C. Y.', 'Zheng, Ken Y. Z.', 'Dong, Tina T. X.', 'Lau, David T. W.', 'Tsim, Karl W. K.']",PLoS One,,,True
580ef02f408295bba21f0ad87b6eba6ba9676163,PMC,Traditional Chinese Medicine Diagnosis “Yang-Xu Zheng”: Significant Prognostic Predictor for Patients with Severe Sepsis and Septic Shock,http://dx.doi.org/10.1155/2013/759748,PMC3824639,24282436,CC BY,"Pathogenesis of sepsis includes complex interaction between pathogen activities and host response, manifesting highly variable signs and symptoms, possibly delaying diagnosis and timely life-saving interventions. This study applies traditional Chinese medicine (TCM) Zheng diagnosis in patients with severe sepsis and septic shock to evaluate its adaptability and use as an early predictor of sepsis mortality. Three-year prospective observational study enrolled 126 septic patients. TCM Zheng diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and blood samples for host response cytokines measurement (tumor necrosis factor-α, Interleukin-6, Interleukin-8, Interleukin-10, Interleukin-18) were collected within 24 hours after admission to Intensive Care Unit. Main outcome was 28-day mortality; multivariate logistic regression analysis served to determine predictive variables of the sepsis mortality. APACHE II score, frequency of Nutrient-phase heat, and Qi-Xu and Yang-Xu Zhengs were significantly higher in nonsurvivors. The multivariate logistic regression analysis identified Yang-Xu Zheng as the outcome predictor. APACHE II score and levels of five host response cytokines between patients with and without Yang-Xu Zheng revealed significant differences. Furthermore, cool extremities and weak pulse, both diagnostic signs of Yang-Xu Zheng, were also proven independent predictors of sepsis mortality. TCM diagnosis “Yang-Xu Zheng” may provide a new mortality predictor for septic patients.",2013 Oct 24,"['Lin, Sunny Jui-Shan', 'Cheng, Yung-Yen', 'Chang, Chih-Hung', 'Lee, Cheng-Hung', 'Huang, Yi-Chia', 'Su, Yi-Chang']",Evid Based Complement Alternat Med,,,True
0807d06a6db06216d0b9399f4658a4ffb581db03,PMC,Defects in Base Excision Repair Sensitize Cells to Manganese in S. cerevisiae,http://dx.doi.org/10.1155/2013/295635,PMC3825218,24282812,CC BY,"Manganese (Mn) is essential for normal physiologic functioning; therefore, deficiencies and excess intake of manganese can result in disease. In humans, prolonged exposure to manganese causes neurotoxicity characterized by Parkinson-like symptoms. Mn(2+) has been shown to mediate DNA damage possibly through the generation of reactive oxygen species. In a recent publication, we showed that Mn induced oxidative DNA damage and caused lesions in thymines. This study further investigates the mechanisms by which cells process Mn(2+)-mediated DNA damage using the yeast S. cerevisiae. The strains most sensitive to Mn(2+) were those defective in base excision repair, glutathione synthesis, and superoxide dismutase mutants. Mn(2+) caused a dose-dependent increase in the accumulation of mutations using the CAN1 and lys2-10A mutator assays. The spectrum of CAN1 mutants indicates that exposure to Mn results in accumulation of base substitutions and frameshift mutations. The sensitivity of cells to Mn(2+) as well as its mutagenic effect was reduced by N-acetylcysteine, glutathione, and Mg(2+). These data suggest that Mn(2+) causes oxidative DNA damage that requires base excision repair for processing and that Mn interferes with polymerase fidelity. The status of base excision repair may provide a biomarker for the sensitivity of individuals to manganese.",2013 Oct 27,"['Stephenson, Adrienne P.', 'Mazu, Tryphon K.', 'Miles, Jana S.', 'Freeman, Miles D.', 'Reams, R. Renee', 'Flores-Rozas, Hernan']",Biomed Res Int,,,True
c08002cc1b2282d646514bf4f2abde54ac144994,PMC,Recombinant lentogenic Newcastle disease virus expressing Ebola virus GP infects cells independently of exogenous trypsin and uses macropinocytosis as the major pathway for cell entry,http://dx.doi.org/10.1186/1743-422X-10-331,PMC3826533,24209904,CC BY,"BACKGROUND: Using reverse genetics, we generated a recombinant low-pathogenic LaSota strain Newcastle disease virus (NDV) expressing the glycoprotein (GP) of Ebola virus (EBOV), designated rLa-EBOVGP, and evaluated its biological characteristic in vivo and in vitro. RESULTS: The introduction and expression of the EBOV GP gene did not increase the virulence of the NDV vector in poultry or mice. EBOV GP was incorporated into the particle of the vector virus and the recombinant virus rLa-EBOVGP infected cells and spread within them independently of exogenous trypsin. rLa-EBOVGP is more resistant to NDV antiserum than the vector NDV and is moderately sensitive to EBOV GP antiserum. More importantly, infection with rLa-EBOVGP was markedly inhibited by IPA3, indicating that rLa-EBOVGP uses macropinocytosis as the major internalization pathway for cell entry. CONCLUSIONS: The results demonstrate that EBOV GP in recombinant NDV particles functions independently to mediate the viral infection of the host cells and alters the cell-entry pathway.",2013 Nov 9,"['Wen, Zhiyuan', 'Zhao, Bolin', 'Song, Kun', 'Hu, Xule', 'Chen, Weiye', 'Kong, Dongni', 'Ge, Jinying', 'Bu, Zhigao']",Virol J,,,True
cfafca2d4a79e684fdd5291ae3b69245ff13b61c,PMC,Public Health Response Systems In-Action: Learning from Local Health Departments’ Experiences with Acute and Emergency Incidents,http://dx.doi.org/10.1371/journal.pone.0079457,PMC3827361,24236137,CC BY,"As part of their core mission, public health agencies attend to a wide range of disease and health threats, including those that require routine, acute, and emergency responses. While each incident is unique, the number and type of response activities are finite; therefore, through comparative analysis, we can learn about commonalities in the response patterns that could improve predictions and expectations regarding the resources and capabilities required to respond to future acute events. In this study, we interviewed representatives from more than 120 local health departments regarding their recent experiences with real-world acute public health incidents, such as infectious disease outbreaks, severe weather events, chemical spills, and bioterrorism threats. We collected highly structured data on key aspects of the incident and the public health response, particularly focusing on the public health activities initiated and community partners engaged in the response efforts. As a result, we are able to make comparisons across event types, create response profiles, and identify functional and structural response patterns that have import for future public health preparedness and response. Our study contributes to clarifying the complexity of public health response systems and our analysis reveals the ways in which these systems are adaptive to the character of the threat, resulting in differential activation of functions and partners based on the type of incident. Continued and rigorous examination of the experiences of health departments throughout the nation will refine our very understanding of what the public health response system is, will enable the identification of organizational and event inputs to performance, and will allow for the construction of rich, relevant, and practical models of response operations that can be employed to strengthen public health systems.",2013 Nov 13,"['Hunter, Jennifer C.', 'Yang, Jane E.', 'Crawley, Adam W.', 'Biesiadecki, Laura', 'Aragón, Tomás J.']",PLoS One,,,True
00fcc6277c19f6b180232d7a6fe0b0abfafb21f7,PMC,Clinical Features and Factors Associated with Severity and Fatality among Patients with Severe Fever with Thrombocytopenia Syndrome Bunyavirus Infection in Northeast China,http://dx.doi.org/10.1371/journal.pone.0080802,PMC3827460,24236203,CC BY,"BACKGROUND: In 2009, severe fever with thrombocytopenia syndrome virus (SFTSV) was identified as a novel member of the genus phlebovirus in the Bunyaviridae family in China. The detailed clinical features of cases with SFTSV infection have not been well described, and the risk factors for severity among patients and fatality among severe patients remain to be determined. METHODOLOGY/PRINCIPAL FINDINGS: Clinical and laboratory features of 115 hospitalized patients with SFTSV infection during the period from June 2010 to December 2011 in Northeast China were retrospectively reviewed. We assessed the risk factors associated with severity in confirmed cases and fatality in severe cases by multivariate analysis. One hundred and three (89.6%) of 115 patients presented with multiple organ dysfunction, and 22 (19.1%) of 115 proceeded to the stage of life threatening multiple organ failure. Of the 115 patients, 14 fatalities (12.2%) were reported. Multivariate analysis demonstrated that the independent predictors of risk for severity were: albumin ≤30 g/l (OR, 8.09; 95% CI, 2.58-25.32), APTT ≥ 66 seconds (OR, 14.28; 95% CI, 3.28-62.24), sodium ≤130 mmol/l (OR, 5.44; 95% CI, 1.38-21.40), and presence of neurological manifestations (OR, 7.70; 95% CI, 1.91-31.12). Among patients with severe disease, presence of acute lung injury/acute respiratory distress syndrome (HR, 4.59; 95% CI, 1.48–14.19) and disseminated intravascular coagulation (HR, 4.24; 95% CI, 1.38–13.03) were independently associated with fatality. CONCLUSIONS/SIGNIFICANCE: SFTSV infection may present with more severe symptoms and laboratory abnormalities than hitherto reported. Due to infection with a novel bunyavirus, the patients may sufferer multiple organ dysfunction and die of multiple organ failure. In the clinical assessment of any case of SFTS, independent factors relating to prognosis need to be taken into account by clinicians.",2013 Nov 13,"['Deng, Baocheng', 'Zhou, Bo', 'Zhang, Shujun', 'Zhu, Ying', 'Han, Leqiang', 'Geng, Yingzhi', 'Jin, Zhenan', 'Liu, Hongbo', 'Wang, Donglei', 'Zhao, Yitong', 'Wen, Ying', 'Cui, Wei', 'Zhou, Ying', 'Gu, Qiuhong', 'Sun, Cuiming', 'Lu, Xu', 'Wang, Wen', 'Wang, Yu', 'Li, Chengbo', 'Wang, Yanli', 'Yao, Wenqing', 'Liu, Pei']",PLoS One,,,True
4f5a550869a4ff5f8c754a9aa89453486cab2985,PMC,Limited Promiscuity of HLA-DRB1 Presented Peptides Derived of Blood Coagulation Factor VIII,http://dx.doi.org/10.1371/journal.pone.0080239,PMC3828219,24244658,CC BY,"The formation of inhibitory antibodies directed against coagulation factor VIII (FVIII) is a severe complication in the treatment of hemophilia A patients. The induction of anti-FVIII antibodies is a CD4(+) T cell-dependent process. Activation of FVIII-specific CD4(+) T cells is dependent on the presentation of FVIII-derived peptides on MHC class II by antigen-presenting cells. Previously, we have shown that FVIII-pulsed human monocyte-derived dendritic cells can present peptides from several FVIII domains. In this study we show that FVIII peptides are presented on immature as well as mature dendritic cells. In immature dendritic cells half of the FVIII-loaded MHC class II molecules are retained within the cell, whereas in LPS-matured dendritic cells the majority of MHC class II/peptide complexes is present on the plasma membrane. Time-course studies revealed that presentation of FVIII-derived peptides was optimal between 12 and 24 hours after maturation but persisted for at least 96 hours. We also show that macrophages are able to internalize FVIII as efficiently as dendritic cells, however FVIII was presented on MHC class II with a lower efficiency and with different epitopes compared to dendritic cells. In total, 48 FVIII core-peptides were identified using a DCs derived of 8 different donors. Five HLA-promiscuous FVIII peptide regions were found – these were presented by at least 4 out of 8 donors. The remaining 42 peptide core regions in FVIII were presented by DCs derived from a single (30 peptides) or two to three donors (12 peptides). Overall, our findings show that a broad repertoire of FVIII peptides can be presented on HLA-DR.",2013 Nov 14,"['van Haren, Simon D.', 'Wroblewska, Aleksandra', 'Herczenik, Eszter', 'Kaijen, Paul H.', 'Ruminska, Aleksandra', 'ten Brinke, Anja', 'Meijer, Alexander B.', 'Voorberg, Jan']",PLoS One,,,True
691bcdc9ee856e121db71833a0c56c43c3c25555,PMC,Limited Promiscuity of HLA-DRB1 Presented Peptides Derived of Blood Coagulation Factor VIII,http://dx.doi.org/10.1371/journal.pone.0080239,PMC3828219,24244658,CC BY,"The formation of inhibitory antibodies directed against coagulation factor VIII (FVIII) is a severe complication in the treatment of hemophilia A patients. The induction of anti-FVIII antibodies is a CD4(+) T cell-dependent process. Activation of FVIII-specific CD4(+) T cells is dependent on the presentation of FVIII-derived peptides on MHC class II by antigen-presenting cells. Previously, we have shown that FVIII-pulsed human monocyte-derived dendritic cells can present peptides from several FVIII domains. In this study we show that FVIII peptides are presented on immature as well as mature dendritic cells. In immature dendritic cells half of the FVIII-loaded MHC class II molecules are retained within the cell, whereas in LPS-matured dendritic cells the majority of MHC class II/peptide complexes is present on the plasma membrane. Time-course studies revealed that presentation of FVIII-derived peptides was optimal between 12 and 24 hours after maturation but persisted for at least 96 hours. We also show that macrophages are able to internalize FVIII as efficiently as dendritic cells, however FVIII was presented on MHC class II with a lower efficiency and with different epitopes compared to dendritic cells. In total, 48 FVIII core-peptides were identified using a DCs derived of 8 different donors. Five HLA-promiscuous FVIII peptide regions were found – these were presented by at least 4 out of 8 donors. The remaining 42 peptide core regions in FVIII were presented by DCs derived from a single (30 peptides) or two to three donors (12 peptides). Overall, our findings show that a broad repertoire of FVIII peptides can be presented on HLA-DR.",2013 Nov 14,"['van Haren, Simon D.', 'Wroblewska, Aleksandra', 'Herczenik, Eszter', 'Kaijen, Paul H.', 'Ruminska, Aleksandra', 'ten Brinke, Anja', 'Meijer, Alexander B.', 'Voorberg, Jan']",PLoS One,,,False
d4b76917de146cdbe4c922c15ac3d87d3d483446,PMC,Transcriptional profiling of feline infectious peritonitis virus infection in CRFK cells and in PBMCs from FIP diagnosed cats,http://dx.doi.org/10.1186/1743-422X-10-329,PMC3829811,24209771,CC BY,"BACKGROUND: Feline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV). Currently, the viruses virulence determinants and host gene expressions during FIPV infection are not fully understood. METHODS: RNA sequencing of Crandell Rees Feline Kidney (CRFK) cells, infected with FIPV strain 79–1146 at 3 hours post infection (h.p.i), were sequenced using the Illumina next generation sequencing approach. Bioinformatic’s analysis, based on Felis catus 2X annotated shotgun reference genome, using CLC bio Genome Workbench mapped both control and infected cell reads to 18899 genes out of 19046 annotated genes. Kal’s Z test statistical analysis was used to analyse the differentially expressed genes from the infected CRFK cells. Real time RT-qPCR was developed for further transcriptional profiling of three genes (PD-1, PD-L1 and A3H) in infected CRFK cells and Peripheral Blood Mononuclear Cells (PBMCs) from healthy and FIP-diseased cats. RESULTS: Based on Kal’s Z-test, with False Discovery Rate (FDR) <0.05 and >1.99 fold change on gene expressions, a total of 61 genes were differentially expressed by both samples, where 44 genes were up-regulated and the remainder were down-regulated. Most genes were closely clustered together, suggesting a homogeneous expression. The majority of the genes that were significantly regulated, were those associated with monocytes-macrophage and Th1 cell functions, and the regulation of apoptosis. Real time RT-qPCR developed focusing on 2 up-regulated genes (PD-L1 and A3H) together with an apoptosis associated gene PD-1 expressions in FIPV infected CRFK cells and in PBMCs from healthy and FIP diagnosed cats produced concordant results with transcriptome data. CONCLUSION: The possible roles of these genes, and their importance in feline coronaviruses infection, are discussed.",2013 Nov 9,"['Harun, Mohammad Syamsul Reza', 'Kuan, Choong Oi', 'Selvarajah, Gayathri Thevi', 'Wei, Tan Sheau', 'Arshad, Siti Suri', 'Bejo, Mohd Hair', 'Omar, Abdul Rahman']",Virol J,,,True
28a0bf1e235fe876fff1127346bb3bac0b6e5072,PMC,Elucidating the Interacting Domains of Chandipura Virus Nucleocapsid Protein,http://dx.doi.org/10.1155/2013/594319,PMC3830837,24288532,CC BY,"The nucleocapsid (N) protein of Chandipura virus (CHPV) plays a crucial role in viral life cycle, besides being an important structural component of the virion through proper organization of its interactions with other viral proteins. In a recent study, the authors had mapped the associations among CHPV proteins and shown that N protein interacts with four of the viral proteins: N, phosphoprotein (P), matrix protein (M), and glycoprotein (G). The present study aimed to distinguish the regions of CHPV N protein responsible for its interactions with other viral proteins. In this direction, we have generated the structure of CHPV N protein by homology modeling using SWISS-MODEL workspace and Accelrys Discovery Studio client 2.55 and mapped the domains of N protein using PiSQRD. The interactions of N protein fragments with other proteins were determined by ZDOCK rigid-body docking method and validated by yeast two-hybrid and ELISA. The study revealed a unique binding site, comprising of amino acids 1–30 at the N terminus of the nucleocapsid protein (N1) that is instrumental in its interactions with N, P, M, and G proteins. It was also observed that N2 associates with N and G proteins while N3 interacts with N, P, and M proteins.",2013 Oct 28,"['Kumar, Kapila', 'Rajasekharan, Sreejith', 'Gulati, Sahil', 'Rana, Jyoti', 'Gabrani, Reema', 'Jain, Chakresh K.', 'Gupta, Amita', 'Chaudhary, Vijay K.', 'Gupta, Sanjay']",Adv Virol,,,True
6531f45674dda196c08f5a81a18eeea88ee6bb55,PMC,Targeting Toll-Like Receptors: Promising Therapeutic Strategies for the Management of Sepsis-Associated Pathology and Infectious Diseases,http://dx.doi.org/10.3389/fimmu.2013.00387,PMC3831162,24302927,CC BY,"Toll-like receptors (TLRs) are pattern recognition receptors playing a fundamental role in sensing microbial invasion and initiating innate and adaptive immune responses. TLRs are also triggered by danger signals released by injured or stressed cells during sepsis. Here we focus on studies developing TLR agonists and antagonists for the treatment of infectious diseases and sepsis. Positioned at the cell surface, TLR4 is essential for sensing lipopolysaccharide of Gram-negative bacteria, TLR2 is involved in the recognition of a large panel of microbial ligands, while TLR5 recognizes flagellin. Endosomal TLR3, TLR7, TLR8, TLR9 are specialized in the sensing of nucleic acids produced notably during viral infections. TLR4 and TLR2 are favorite targets for developing anti-sepsis drugs, and antagonistic compounds have shown efficient protection from septic shock in pre-clinical models. Results from clinical trials evaluating anti-TLR4 and anti-TLR2 approaches are presented, discussing the challenges of study design in sepsis and future exploitation of these agents in infectious diseases. We also report results from studies suggesting that the TLR5 agonist flagellin may protect from infections of the gastrointestinal tract and that agonists of endosomal TLRs are very promising for treating chronic viral infections. Altogether, TLR-targeted therapies have a strong potential for prevention and intervention in infectious diseases, notably sepsis.",2013 Nov 18,"['Savva, Athina', 'Roger, Thierry']",Front Immunol,,,True
c52ffa67fea523c74bd0c0f45033183f403692ed,PMC,Lung progenitors from lambs can differentiate into specialized alveolar or bronchiolar epithelial cells,http://dx.doi.org/10.1186/1746-6148-9-224,PMC3831758,24206786,CC BY,"BACKGROUND: Airways progenitors may be involved in embryogenesis and lung repair. The characterization of these important populations may enable development of new therapeutics to treat acute or chronic lung disease. In this study, we aimed to establish the presence of bronchioloalveolar progenitors in ovine lungs and to characterize their potential to differentiate into specialized cells. RESULTS: Lung cells were studied using immunohistochemistry on frozen sections of the lung. Immunocytochemistry and flow cytometry were conducted on ex-vivo derived pulmonary cells. The bronchioloalveolar progenitors were identified by their co-expression of CCSP, SP-C and CD34. A minor population of CD34(pos)/SP-C(pos)/CCSP(pos) cells (0.33% ± 0.31) was present ex vivo in cell suspensions from dissociated lungs. Using CD34 magnetic positive-cell sorting, undifferentiated SP-C(pos)/CCSP(pos) cells were purified (>80%) and maintained in culture. Using synthetic media and various extracellular matrices, SP-C(pos)/CCSP(pos) cells differentiated into either club cells (formerly named Clara cells) or alveolar epithelial type-II cells. Furthermore, these ex vivo and in vitro derived bronchioloalveolar progenitors expressed NANOG, OCT4 and BMI1, specifically described in progenitors or stem cells, and during lung development. CONCLUSIONS: We report for the first time in a large animal the existence of bronchioloalveolar progenitors with dual differentiation potential and the expression of specialized genes. These newly described cell population in sheep could be implicated in regeneration of the lung following lesions or in development of diseases such as cancers.",2013 Nov 8,"['Archer, Fabienne', 'Abi-Rizk, Alain', 'Desloire, Sophie', 'Dolmazon, Christine', 'Gineys, Barbara', 'Guiguen, François', 'Cottin, Vincent', 'Mornex, Jean-François', 'Leroux, Caroline']",BMC Vet Res,,,True
324deb63a4686d7efc7c32b8e20bdc7e96e1fb7e,PMC,Effects of Space Flight on the Chemical Constituents and Anti-Inflammatory Activity of Licorice (Glycyrrhiza uralensis Fisch),,PMC3832146,24250485,CC BY,"Licorice, the oldest Chinese traditional medicine, is widely used in the treatment of human diseases. Due to the deficiency of wild resource, selecting and breeding becomes a key issue to expanding the supply of licorice. Spaceflight technology will become a new method for medicinal plants. The aim of this study was to investigate the effect of spaceflight on the components and anti-inflammatory activity in licorice. After flowing on a recoverable satellite for 18 days, licorice seeds were germinated and grown to maturity and the parallel ground-based seeds were also planted under the same conditions. The main components in licorice root were analyzed through HPLC. The contents of two components in spaceflight groups were higher than that of the ground control ones. Three acute inflammatory models including xylene-induced auricular edema, carrageenan-induced paw edema and acetic acid-induced vascular permeability were utilized to compare the anti-inflammatory activity of licorice pre and post spaceflight. The licorice extract showed the significant anti-inflammation activity. After the spaceflight, the pharmacological activity of licorice got higher than that of the ground control one. All of the models gained the tendency that the spaceflight group of species Hangjinqi had the strongest activity than other groups. The research provided the scientific data for a new breeding of medicinal plant through the spaceflight and indicated that the technology of space flight may be a new effective method for the breeding and cultivation of licorice.",2012 Spring,"['Zhang, Jingze', 'Gao, Wenyuan', 'Yan, Shuo', 'Zhao, Yaxin']",Iran J Pharm Res,,,True
810749401200c77f19d5a7950070e0c2d4d2629e,PMC,Ubiquitin-Specific Proteases 25 Negatively Regulates Virus-Induced Type I Interferon Signaling,http://dx.doi.org/10.1371/journal.pone.0080976,PMC3832446,24260525,CC BY,"Ubiquitination and deubiquitination have emerged as critical regulatory processes in the virus-triggered type I interferon (IFN) induction pathway. In this study, we carried out a targeted siRNA screen of 54 ubiquitin-specific proteases (USPs) and identified USP25 as a negative regulator of the virus-triggered type I IFN signaling pathway. Overexpression of USP25 inhibited virus-induced activation of IFN-β, interferon regulation factor 3 (IRF3) and nuclear factor-kappa B (NF-κB), as well as the phosphorylation of IRF3 and NF-κB subunit p65. Furthermore, Knockdown of USP25 potentiated virus-induced induction of the IFN-β. In addition, detailed analysis demonstrated that USP25 cleaved lysine 48- and lysine 63-linked polyubiquitin chains in vitro and in vivo, and its deubiquitinating enzyme (DUB) activity, were dependent on a cysteine residue (Cys178) and a histidine residue (His607). USP25 mutants lacking DUB activity lost the ability to block virus-induced type I IFN to some degree. Mechanistically, USP25 deubiquitinated retinoic acid-inducible gene I (RIG-I), tumornecrosis factor (TNF) receptor-associated factor 2 (TRAF2), and TRAF6 to inhibit RIG-I-like receptor-mediated IFN signaling. Our findings suggest that USP25 is a novel DUB negatively regulating virus-induced type I IFN production.",2013 Nov 18,"['Zhong, Huijuan', 'Wang, Dang', 'Fang, Liurong', 'Zhang, Huan', 'Luo, Rui', 'Shang, Min', 'Ouyang, Chao', 'Ouyang, Haiping', 'Chen, Huanchun', 'Xiao, Shaobo']",PLoS One,,,True
7274f439641a1f4dc180a94cafe9b69d37e60415,PMC,Novel Virus Discovery and Genome Reconstruction from Field RNA Samples Reveals Highly Divergent Viruses in Dipteran Hosts,http://dx.doi.org/10.1371/journal.pone.0080720,PMC3832450,24260463,CC BY,"We investigated whether small RNA (sRNA) sequenced from field-collected mosquitoes and chironomids (Diptera) can be used as a proxy signature of viral prevalence within a range of species and viral groups, using sRNAs sequenced from wild-caught specimens, to inform total RNA deep sequencing of samples of particular interest. Using this strategy, we sequenced from adult Anopheles maculipennis s.l. mosquitoes the apparently nearly complete genome of one previously undescribed virus related to chronic bee paralysis virus, and, from a pool of Ochlerotatus caspius and Oc. detritus mosquitoes, a nearly complete entomobirnavirus genome. We also reconstructed long sequences (1503-6557 nt) related to at least nine other viruses. Crucially, several of the sequences detected were reconstructed from host organisms highly divergent from those in which related viruses have been previously isolated or discovered. It is clear that viral transmission and maintenance cycles in nature are likely to be significantly more complex and taxonomically diverse than previously expected.",2013 Nov 18,"['Cook, Shelley', 'Chung, Betty Y.-W.', 'Bass, David', 'Moureau, Gregory', 'Tang, Shuoya', 'McAlister, Erica', 'Culverwell, C. Lorna', 'Glücksman, Edvard', 'Wang, Hui', 'Brown, T. David K.', 'Gould, Ernest A.', 'Harbach, Ralph E.', 'de Lamballerie, Xavier', 'Firth, Andrew E.']",PLoS One,,,True
6a54a1fdb5e1476e36b632b0fb061da5b3b69b5c,PMC,Prevalence of Herpes and Respiratory Viruses in Induced Sputum among Hospitalized Children with Non Typical Bacterial Community-Acquired Pneumonia,http://dx.doi.org/10.1371/journal.pone.0079477,PMC3832587,24260230,CC BY,"OBJECTIVE: Few comprehensive studies have searched for viruses in infants and young children with community-acquired pneumonia (CAP) in China. The aim of this study was to investigate the roles of human herpes viruses (HHVs) and other respiratory viruses in CAP not caused by typical bacterial infection and to determine their prevalence and clinical significance. METHODS: Induced sputum (IS) samples were collected from 354 hospitalised patients (infants, n = 205; children, n = 149) with respiratory illness (CAP or non-CAP) admitted to Wenling Hospital of China. We tested for HHVs and respiratory viruses using PCR-based assays. The epidemiological profiles were also analysed. RESULTS: High rate of virus detection (more than 98%) and co-infection (more than 80%) were found among IS samples from 354 hospitalised infants and children with respiratory illness in this study. Of 273 CAP samples tested, CMV (91.6%), HHV-6 (50.9%), RSV (37.4%), EBV (35.5%), HBoV (28.2%), HHV-7 (18.3%) and rhinovirus (17.2%) were the most commonly detected viruses. Of 81 non- CAP samples tested, CMV (63%), RSV (49.4%), HHV-6 (42%), EBV (24.7%), HHV-7 (13.6%) and HBoV (8.6%) were the dominant viruses detected. The prevalence of several viral agents (rhinovirus, bocavirus, adenovirus and CMV) among IS samples of CAP were significantly higher than that of non-CAP control group. We also found the prevalence of RSV coinfection with HHVs was also higher among CAP group than that of non-CAP control. CONCLUSIONS: With sensitive molecular detection techniques and IS samples, high rates of viral identification were achieved in infants and young children with respiratory illness in a rural area of China. The clinical significance of rhinovirus, bocavirus, adenovirus and HHV (especially CMV) infections should receive greater attention in future treatment and prevention studies of CAP in infants and children.",2013 Nov 18,"['Zhou, Weimin', 'Lin, Feng', 'Teng, Lingfang', 'Li, Hua', 'Hou, Jianyi', 'Tong, Rui', 'Zheng, Changhua', 'Lou, Yongliang', 'Tan, Wenjie']",PLoS One,,,True
41d0c75e25a257485a79211632b5c9ed93d4df14,PMC,The biodistribution of self-assembling protein nanoparticles shows they are promising vaccine platforms,http://dx.doi.org/10.1186/1477-3155-11-36,PMC3832906,24219600,CC BY,"BACKGROUND: Because of the need to limit side-effects, nanoparticles are increasingly being studied as drug-carrying and targeting tools. We have previously reported on a scheme to produce protein-based self-assembling nanoparticles that can act as antigen display platforms. Here we attempted to use the same system for cancer-targeting, making use of a C-terminal bombesin peptide that has high affinity for a receptor known to be overexpressed in certain tumors, as well as an N-terminal polyhistidine tag that can be used for radiolabeling with technetium tricarbonyl. RESULTS: In order to increase circulation time, we experimented with PEGylated and unPEGylated varities typo particle. We also tested the effect of incorporating different numbers of bombesins per nanoparticle. Biophysical characterization determined that all configurations assemble into regular particles with relatively monodisperse size distributions, having peaks of about 33 – 36 nm. The carbonyl method used for labeling produced approximately 80% labeled nanoparticles. In vitro, the nanoparticles showed high binding, both specific and non-specific, to PC-3 prostate cancer cells. In vivo, high uptake was observed for all nanoparticle types in the spleens of CD-1 nu/nu mice, decreasing significantly over the course of 24 hours. High uptake was also observed in the liver, while only low uptake was seen in both the pancreas and a tumor xenograft. CONCLUSIONS: The data suggest that the nanoparticles are non-specifically taken up by the reticuloendothelial system. Low uptake in the pancreas and tumor indicate that there is little or no specific targeting. PEGylation or increasing the amount of bombesins per nanoparticle did not significantly improve targeting. In particular, the uptake in the spleen, which is a primary organ of the immune system, highlights the potential of the nanoparticles as vaccine carriers. Also, the decrease in liver and spleen radioactivity with time implies that the nanoparticles are broken down and cleared. This is an important finding, as it shows that the nanoparticles can be safely used as a vaccine platform without the risk of prolonged side effects. Furthermore, it demonstrates that technetium carbonyl radiolabeling of our protein-based nanoparticles can be used to evaluate their pharmacokinetic properties in vivo.",2013 Nov 12,"['Yang, Yongkun', 'Neef, Tobias', 'Mittelholzer, Christian', 'Garcia Garayoa, Elisa', 'Bläuenstein, Peter', 'Schibli, Roger', 'Aebi, Ueli', 'Burkhard, Peter']",J Nanobiotechnology,,,True
2d2b70166db15be7908f748930e9c56a300e5851,PMC,"Twentieth anniversary of the European Union health mandate: taking stock of perceived achievements, failures and missed opportunities – a qualitative study",http://dx.doi.org/10.1186/1471-2458-13-1074,PMC3833669,24225055,CC BY,"BACKGROUND: The European Union (EU) health mandate was initially defined in the Maastricht Treaty in 1992. The twentieth anniversary of the Treaty offers a unique opportunity to take stock of EU health actions by giving an overview of influential public health related EU-level policy outputs and a summary of policy outputs or actions perceived as an achievement, a failure or a missed opportunity. METHODS: Semi-structured expert interviews (N = 20) were conducted focusing on EU-level actions that were relevant for health. Respondents were asked to name EU policies or actions that they perceived as an achievement, a failure or a missed opportunity. A directed content analysis approach was used to identify expert perceptions on achievements, failures and missed opportunities in the interviews. Additionally, a nominal group technique was applied to identify influential and public health relevant EU-level policy outputs. RESULTS: The ranking of influential policy outputs resulted in top positions of adjudications and legislations, agencies, European Commission (EC) programmes and strategies, official networks, cooperative structures and exchange efforts, the work on health determinants and uptake of scientific knowledge. The assessment of EU health policies as being an achievement, a failure or a missed opportunity was often characterized by diverging respondent views. Recurring topics that emerged were the Directorate General for Health and Consumers (DG SANCO), EU agencies, life style factors, internal market provisions as well as the EU Directive on patients’ rights in cross-border healthcare. Among these recurring topics, expert perceptions on the establishment of DG SANCO, EU public health agencies, and successes in tobacco control were dominated by aspects of achievements. The implementation status of the Health in All Policy approach was perceived as a missed opportunity. CONCLUSIONS: When comparing the emerging themes from the interviews conducted with the responsibilities defined in the EU health mandate, one can identify that these responsibilities were only partly fulfilled or acknowledged by the respondents. In general, the EU is a recognized public health player in Europe which over the past two decades, has begun to develop competencies in supporting, coordinating and supplementing member state health actions. However, the assurance of health protection in other European policies seems to require further development.",2013 Nov 14,"['Rosenkötter, Nicole', 'Clemens, Timo', 'Sørensen, Kristine', 'Brand, Helmut']",BMC Public Health,,,True
801aad4fa6fab8d6d0973eb4df2178454195e037,PMC,Spironolactone Attenuates Bleomycin-Induced Pulmonary Injury Partially via Modulating Mononuclear Phagocyte Phenotype Switching in Circulating and Alveolar Compartments,http://dx.doi.org/10.1371/journal.pone.0081090,PMC3834272,24260540,CC BY,"BACKGROUND: Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis. Mineralocorticoid receptor (MR) has been reported as a target to regulate macrophage polarization. The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis. METHODOLOGY/PRINCIPAL FINDINGS: We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF) from C57BL/6 mice. Then, a pharmacological intervention study using spironolactone (20mg/kg/day by oral gavage) revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels) and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson’ trichrome staining) in bleomycin treated (2.5mg/kg, via oropharyngeal instillation) male C57BL/6 mice. Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C(hi) monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+) of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c-) remained unaffected by spironolactone during investigation. CONCLUSIONS/SIGNIFICANCE: The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching.",2013 Nov 19,"['Ji, Wen-Jie', 'Ma, Yong-Qiang', 'Zhou, Xin', 'Zhang, Yi-Dan', 'Lu, Rui-Yi', 'Guo, Zhao-Zeng', 'Sun, Hai-Ying', 'Hu, Dao-Chuan', 'Yang, Guo-Hong', 'Li, Yu-Ming', 'Wei, Lu-Qing']",PLoS One,,,True
1c8a0fb2f60c243f71d16d5fefb5b51d7978869e,PMC,Proteome and phosphoproteome analysis of honeybee (Apis mellifera) venom collected from electrical stimulation and manual extraction of the venom gland,http://dx.doi.org/10.1186/1471-2164-14-766,PMC3835400,24199871,CC BY,"BACKGROUND: Honeybee venom is a complicated defensive toxin that has a wide range of pharmacologically active compounds. Some of these compounds are useful for human therapeutics. There are two major forms of honeybee venom used in pharmacological applications: manually (or reservoir disrupting) extracted glandular venom (GV), and venom extracted through the use of electrical stimulation (ESV). A proteome comparison of these two venom forms and an understanding of the phosphorylation status of ESV, are still very limited. Here, the proteomes of GV and ESV were compared using both gel-based and gel-free proteomics approaches and the phosphoproteome of ESV was determined through the use of TiO(2) enrichment. RESULTS: Of the 43 proteins identified in GV, < 40% were venom toxins, and > 60% of the proteins were non-toxic proteins resulting from contamination by gland tissue damage during extraction and bee death. Of the 17 proteins identified in ESV, 14 proteins (>80%) were venom toxic proteins and most of them were found in higher abundance than in GV. Moreover, two novel proteins (dehydrogenase/reductase SDR family member 11-like and histone H2B.3-like) and three novel phosphorylation sites (icarapin (S43), phospholipase A-2 (T145), and apamin (T23)) were identified. CONCLUSIONS: Our data demonstrate that venom extracted manually is different from venom extracted using ESV, and these differences may be important in their use as pharmacological agents. ESV may be more efficient than GV as a potential pharmacological source because of its higher venom protein content, production efficiency, and without the need to kill honeybee. The three newly identified phosphorylated venom proteins in ESV may elicit a different immune response through the specific recognition of antigenic determinants. The two novel venom proteins extend our proteome coverage of honeybee venom.",2013 Nov 7,"['Li, Rongli', 'Zhang, Lan', 'Fang, Yu', 'Han, Bin', 'Lu, Xiaoshan', 'Zhou, Tiane', 'Feng, Mao', 'Li, Jianke']",BMC Genomics,,,True
d2597e291d5073395da85f2db0f523f01530a3f6,PMC,A Genome-Wide Analysis of RNA Pseudoknots That Stimulate Efficient −1 Ribosomal Frameshifting or Readthrough in Animal Viruses,http://dx.doi.org/10.1155/2013/984028,PMC3835772,24298557,CC BY,"Programmed −1 ribosomal frameshifting (PRF) and stop codon readthrough are two translational recoding mechanisms utilized by some RNA viruses to express their structural and enzymatic proteins at a defined ratio. Efficient recoding usually requires an RNA pseudoknot located several nucleotides downstream from the recoding site. To assess the strategic importance of the recoding pseudoknots, we have carried out a large scale genome-wide analysis in which we used an in-house developed program to detect all possible H-type pseudoknots within the genomic mRNAs of 81 animal viruses. Pseudoknots are detected downstream from ~85% of the recoding sites, including many previously unknown pseudoknots. ~78% of the recoding pseudoknots are the most stable pseudoknot within the viral genomes. However, they are not as strong as some designed pseudoknots that exhibit roadblocking effect on the translating ribosome. Strong roadblocking pseudoknots are not detected within the viral genomes. These results indicate that the decoding pseudoknots have evolved to possess optimal stability for efficient recoding. We also found that the sequence at the gag-pol frameshift junction of HIV1 harbors potential elaborated pseudoknots encompassing the frameshift site. A novel mechanism is proposed for possible involvement of the elaborated pseudoknots in the HIV1 PRF event.",2013 Nov 4,"['Huang, Xiaolan', 'Cheng, Qiang', 'Du, Zhihua']",Biomed Res Int,,,False
01b5ae0cce289ca9cdcebc4079f960e833cfbd79,PMC,A Genome-Wide Analysis of RNA Pseudoknots That Stimulate Efficient −1 Ribosomal Frameshifting or Readthrough in Animal Viruses,http://dx.doi.org/10.1155/2013/984028,PMC3835772,24298557,CC BY,"Programmed −1 ribosomal frameshifting (PRF) and stop codon readthrough are two translational recoding mechanisms utilized by some RNA viruses to express their structural and enzymatic proteins at a defined ratio. Efficient recoding usually requires an RNA pseudoknot located several nucleotides downstream from the recoding site. To assess the strategic importance of the recoding pseudoknots, we have carried out a large scale genome-wide analysis in which we used an in-house developed program to detect all possible H-type pseudoknots within the genomic mRNAs of 81 animal viruses. Pseudoknots are detected downstream from ~85% of the recoding sites, including many previously unknown pseudoknots. ~78% of the recoding pseudoknots are the most stable pseudoknot within the viral genomes. However, they are not as strong as some designed pseudoknots that exhibit roadblocking effect on the translating ribosome. Strong roadblocking pseudoknots are not detected within the viral genomes. These results indicate that the decoding pseudoknots have evolved to possess optimal stability for efficient recoding. We also found that the sequence at the gag-pol frameshift junction of HIV1 harbors potential elaborated pseudoknots encompassing the frameshift site. A novel mechanism is proposed for possible involvement of the elaborated pseudoknots in the HIV1 PRF event.",2013 Nov 4,"['Huang, Xiaolan', 'Cheng, Qiang', 'Du, Zhihua']",Biomed Res Int,,,True
7d38e11db887bf824a89621f65d384ef45e14955,PMC,Development and Evaluation of a SYBR Green-Based Real Time RT-PCR Assay for Detection of the Emerging Avian Influenza A (H7N9) Virus,http://dx.doi.org/10.1371/journal.pone.0080028,PMC3835827,24278234,CC BY,"Most recently a novel avian-origin influenza A (H7N9) virus emerged in China and has been associated with lots of human infection and fatal cases. Genetic analysis of the viral genome revealed that this reassortant virus might be better adapted to humans than other avian influenza viruses. Molecular diagnostic methods are thus urgently needed in public health laboratories. In this study, a SYBR green-based one-step real time reverse transcription-PCR (RT-PCR) was developed to detect the novel H7N9 virus. The primer pairs on the basis of the hemagglutinin and neuraminidase gene sequences of H7N9 viruses amplified subtype-specific fragments with Tm values of 80.77±0.06°C for H7 and 81.20±0.17°C for N9 respectively. The standard curves showed a dynamic linear range across 6 log units of RNA copy number (10(6) to 10(1) copies/ µl) with a detection limit of 10 copies per reaction for both H7 and N9 assays by using serial ten-fold diluted in-vitro transcribed viral RNA. In addition, no cross-reactivity was observed with seasonal H1N1, H1N1 pdm09, H3N2, H5N1 and H9N2 viruses as well as other human respiratory viruses. When the assay was further evaluated in H7N9 virus infected clinical samples, positive amplification signals were obtained in all of the specimens with the accordance between H7 and N9 assays. Therefore, the established SYBR green-based real time RT-PCR assay could provide a rapid, sensitive, specific and reliable alternative approach with lower costs for high throughput screening of suspected samples from humans, animals and environments in first line public health laboratories.",2013 Nov 20,"['Zhu, Zheng', 'Fan, Huan', 'Qi, Xian', 'Qi, Yuhua', 'Shi, Zhiyang', 'Wang, Hua', 'Cui, Lunbiao', 'Zhou, Minghao']",PLoS One,,,True
e5526afbb4d770dabb8c34da47c1267ee3342959,PMC,Ultra-Deep Sequencing of Intra-host Rabies Virus Populations during Cross-species Transmission,http://dx.doi.org/10.1371/journal.pntd.0002555,PMC3836733,24278493,CC0,"One of the hurdles to understanding the role of viral quasispecies in RNA virus cross-species transmission (CST) events is the need to analyze a densely sampled outbreak using deep sequencing in order to measure the amount of mutation occurring on a small time scale. In 2009, the California Department of Public Health reported a dramatic increase (350) in the number of gray foxes infected with a rabies virus variant for which striped skunks serve as a reservoir host in Humboldt County. To better understand the evolution of rabies, deep-sequencing was applied to 40 unpassaged rabies virus samples from the Humboldt outbreak. For each sample, approximately 11 kb of the 12 kb genome was amplified and sequenced using the Illumina platform. Average coverage was 17,448 and this allowed characterization of the rabies virus population present in each sample at unprecedented depths. Phylogenetic analysis of the consensus sequence data demonstrated that samples clustered according to date (1995 vs. 2009) and geographic location (northern vs. southern). A single amino acid change in the G protein distinguished a subset of northern foxes from a haplotype present in both foxes and skunks, suggesting this mutation may have played a role in the observed increased transmission among foxes in this region. Deep-sequencing data indicated that many genetic changes associated with the CST event occurred prior to 2009 since several nonsynonymous mutations that were present in the consensus sequences of skunk and fox rabies samples obtained from 20032010 were present at the sub-consensus level (as rare variants in the viral population) in skunk and fox samples from 1995. These results suggest that analysis of rare variants within a viral population may yield clues to ancestral genomes and identify rare variants that have the potential to be selected for if environment conditions change.",2013 Nov 21,"['Borucki, Monica K.', 'Chen-Harris, Haiyin', 'Lao, Victoria', 'Vanier, Gilda', 'Wadford, Debra A.', 'Messenger, Sharon', 'Allen, Jonathan E.']",PLoS Negl Trop Dis,,,True
5e0e39574ffd7d5f3dcdc97d0301507de50e5c54,PMC,The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells,http://dx.doi.org/10.1371/journal.ppat.1003776,PMC3836734,24278022,CC BY,"The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the combination of acidic pH and Env-specific IgG, including that from cervicovaginal and seminal fluids of HIV-1-infected individuals, augmented transcytosis across epithelial cells as much as 20-fold compared with Env-specific IgG at neutral pH or non-specific IgG at either pH. Enhanced transcytosis was observed with clinical HIV-1 isolates, including transmitted/founder strains, and was eliminated in Fc neonatal receptor (FcRn)-knockdown epithelial cells. Non-neutralizing antibodies allowed similar or less transcytosis than neutralizing antibodies. However, the ratio of total:infectious virus was higher for neutralizing antibodies, indicating that they allowed transcytosis while blocking infectivity of transcytosed virus. Immunocytochemistry revealed abundant FcRn expression in columnar epithelia lining the human endocervix and penile urethra. Acidity and Env-specific IgG enhance transcytosis of virus across epithelial cells via FcRn and could facilitate translocation of virus to susceptible target cells following sexual exposure.",2013 Nov 21,"['Gupta, Sandeep', 'Gach, Johannes S.', 'Becerra, Juan C.', 'Phan, Tran B.', 'Pudney, Jeffrey', 'Moldoveanu, Zina', 'Joseph, Sarah B.', 'Landucci, Gary', 'Supnet, Medalyn Jude', 'Ping, Li-Hua', 'Corti, Davide', 'Moldt, Brian', 'Hel, Zdenek', 'Lanzavecchia, Antonio', 'Ruprecht, Ruth M.', 'Burton, Dennis R.', 'Mestecky, Jiri', 'Anderson, Deborah J.', 'Forthal, Donald N.']",PLoS Pathog,,,True
31e1410cb8c22cfaae254381a16e88ec633086e4,PMC,Defining the Range of Pathogens Susceptible to Ifitm3 Restriction Using a Knockout Mouse Model,http://dx.doi.org/10.1371/journal.pone.0080723,PMC3836756,24278312,CC BY,"The interferon-inducible transmembrane (IFITM) family of proteins has been shown to restrict a broad range of viruses in vitro and in vivo by halting progress through the late endosomal pathway. Further, single nucleotide polymorphisms (SNPs) in its sequence have been linked with risk of developing severe influenza virus infections in humans. The number of viruses restricted by this host protein has continued to grow since it was first demonstrated as playing an antiviral role; all of which enter cells via the endosomal pathway. We therefore sought to test the limits of antimicrobial restriction by Ifitm3 using a knockout mouse model. We showed that Ifitm3 does not impact on the restriction or pathogenesis of bacterial (Salmonella typhimurium, Citrobacter rodentium, Mycobacterium tuberculosis) or protozoan (Plasmodium berghei) pathogens, despite in vitro evidence. However, Ifitm3 is capable of restricting respiratory syncytial virus (RSV) in vivo either through directly restricting RSV cell infection, or by exerting a previously uncharacterised function controlling disease pathogenesis. This represents the first demonstration of a virus that enters directly through the plasma membrane, without the need for the endosomal pathway, being restricted by the IFITM family; therefore further defining the role of these antiviral proteins.",2013 Nov 21,"['Everitt, Aaron R.', 'Clare, Simon', 'McDonald, Jacqueline U.', 'Kane, Leanne', 'Harcourt, Katherine', 'Ahras, Malika', 'Lall, Amar', 'Hale, Christine', 'Rodgers, Angela', 'Young, Douglas B.', 'Haque, Ashraful', 'Billker, Oliver', 'Tregoning, John S.', 'Dougan, Gordon', 'Kellam, Paul']",PLoS One,,,True
8613777458478918e5fd17250ca0dc7dcb92e259,PMC,Quantification of Hantaan Virus with a SYBR Green Ⅰ-Based One-Step qRT-PCR Assay,http://dx.doi.org/10.1371/journal.pone.0081525,PMC3836762,24278449,CC BY,"Hantaan virus (HTNV) is a major zoonotic pathogen that causes hemorrhagic fever with renal syndrome (HFRS) in Asia, especially in China. Shaanxi province, which is located in northwest of China, is one of the areas in China most severely afflicted with HFRS epidemics annually. This study aims to establish a quantitative RT-PCR (qRT-PCR) assay to detect HTNV both in cell culture and clinical serum samples. We established a SYBR Green Ⅰ-based one-step qRT-PCR assay that targets the S segment of the HTNV genome for rapid detection and quantification. The HTNV cRNA standards were constructed by in vitro transcription, and the copy numbers of the HTNV cRNA were quantified. Standard curve was generated by determining the mean cycle threshold (Ct) values versus 10-fold serial dilutions of the HTNV cRNA over a range of 1×10(8) to 1×10(3) copies/μl. The standard curve had a reaction efficiency of 102.1%, a correlation coefficient (R(2)) of 0.998, and a slope of -3.273. The coefficient of variation (CV) of the intra- and inter-assays ranged from 0.68% to 3.00% and from 0.86% to 3.21%, respectively. The cycle intervals of the qRT-PCR assay between each dilution ranged from 2.9 to 3.8 cycles, and the lowest detection limit of the qRT-PCR assay was 10 copies/μl. The assay exhibited high specificity that was confirmed by melting curve analysis, and no cross reaction with the Seoul virus (SEOV) and other viruses (HBV, HCV and HIV) was observed. HTNV RNA was also detected in the 27 serum samples of clinical HFRS patients using the assay, and the HTNV RNA viral load ranged from 2.06×10(1) to 1.95×10(5) copies/μl. The SYBR Green Ⅰ-based one-step qRT-PCR assay is a sensitive, specific, reproducible, and simple method for detecting and quantifying HTNV in cell culture and clinical samples.",2013 Nov 21,"['Jiang, Wei', 'Yu, Hai-tao', 'Zhao, Ke', 'Zhang, Ye', 'Du, Hong', 'Wang, Ping-zhong', 'Bai, Xue-fan']",PLoS One,,,True
6da3f66c681b4b60ce1f6f246340517b79b67137,PMC,Chicken Interferon-Inducible Transmembrane Protein 3 Restricts Influenza Viruses and Lyssaviruses In Vitro,http://dx.doi.org/10.1128/JVI.01443-13,PMC3838109,24067955,CC BY,"Interferon-inducible transmembrane protein 3 (IFITM3) is an effector protein of the innate immune system. It confers potent, cell-intrinsic resistance to infection by diverse enveloped viruses both in vitro and in vivo, including influenza viruses, West Nile virus, and dengue virus. IFITM3 prevents cytosolic entry of these viruses by blocking complete virus envelope fusion with cell endosome membranes. Although the IFITM locus, which includes IFITM1, -2, -3, and -5, is present in mammalian species, this locus has not been unambiguously identified or functionally characterized in avian species. Here, we show that the IFITM locus exists in chickens and is syntenic with the IFITM locus in mammals. The chicken IFITM3 protein restricts cell infection by influenza A viruses and lyssaviruses to a similar level as its human orthologue. Furthermore, we show that chicken IFITM3 is functional in chicken cells and that knockdown of constitutive expression in chicken fibroblasts results in enhanced infection by influenza A virus. Chicken IFITM2 and -3 are constitutively expressed in all tissues examined, whereas IFITM1 is only expressed in the bursa of Fabricius, gastrointestinal tract, cecal tonsil, and trachea. Despite being highly divergent at the amino acid level, IFITM3 proteins of birds and mammals can restrict replication of viruses that are able to infect different host species, suggesting IFITM proteins may provide a crucial barrier for zoonotic infections.",2013 Dec,"['Smith, S. E.', 'Gibson, M. S.', 'Wash, R. S.', 'Ferrara, F.', 'Wright, E.', 'Temperton, N.', 'Kellam, P.', 'Fife, M.']",J Virol,,,True
765003fdad3ad535f5fd2d769ed5900e5013dda2,PMC,A Simplified Positive-Sense-RNA Virus Construction Approach That Enhances Analysis Throughput,http://dx.doi.org/10.1128/JVI.02261-13,PMC3838137,24049164,CC BY,"Here we present an approach that advances the throughput of a genetic analysis of a positive-sense RNA virus by simplifying virus construction. It enabled comprehensive dissection of a complex, multigene phenotype through rapid derivation of a large number of chimeric viruses and construction of a mutant library directly from a virus pool. The versatility of the approach described here expands the applicability of diverse genetic approaches to study these viruses.",2013 Dec,"['Siridechadilok, Bunpote', 'Gomutsukhavadee, Methee', 'Sawaengpol, Thunyarat', 'Sangiambut, Sutha', 'Puttikhunt, Chunya', 'Chin-inmanu, Kwanrutai', 'Suriyaphol, Prapat', 'Malasit, Prida', 'Screaton, Gavin', 'Mongkolsapaya, Juthathip']",J Virol,,,True
bf256a0f8fd3ff2faa39f340180e7e19bfa4c295,PMC,The Soluble Form of the EIAV Receptor Encoded by an Alternative Splicing Variant Inhibits EIAV Infection of Target Cells,http://dx.doi.org/10.1371/journal.pone.0079299,PMC3838338,24278125,CC BY,"Equine lentivirus receptor 1 (ELR1) has been identified as the sole receptor for equine infectious anemia virus (EIAV) and is a member of the tumor necrosis factor receptor (TNFR) superfamily. In addition to the previously described membrane-associated form of ELR1, two other major alternative splicing variant mRNAs were identified in equine monocyte-derived macrophages (eMDMs). One major spliced species (ELR1-IN) contained an insertion of 153 nt, which resulted in a premature stop codon situated 561 nt upstream of the predicted membrane spanning domain. The other major species (ELR1-DE) has a deletion of 109 nt that causes a shift of the open reading frame and generates a stop codon 312 nt downstream. Because ELR1-DE presumably encodes a peptide of a mere 23 residues, only ELR1-IN was further analyzed. The expression of a soluble form of ELR1 (sELR1) by ELR1-IN was confirmed by Western blot and immunofluorescence analyses. Similar to ELR1, the transcription level of ELR1-IN varied among individual horses and at different time points in the same individuals. The ratio of ELR1-IN mRNA species to ELR1 mRNA was approximately 1∶2.5. Pre-incubation of the recombinant sELR1 with EIAV significantly inhibited EIAV infection in equine macrophages, the primary in vivo target cell of the virus. Fetal equine dermal (FED) cells are susceptible to EIAV in vitro, and the replication of EIAV in FED cells transiently transfected with ELR1-IN was markedly reduced when compared with replication in cells transfected with the empty vector. Finally, the expression levels of both forms of the EIAV receptor were significantly regulated by infection with this virus. Taken together, our data indicate that sELR1 acts as a secreted cellular factor that inhibits EIAV infection in host cells.",2013 Nov 22,"['Lin, Yue-Zhi', 'Yang, Fei', 'Zhang, Shu-Qin', 'Sun, Liu-Ke', 'Wang, Xue-Feng', 'Du, Cheng', 'Zhou, Jian-Hua']",PLoS One,,,True
9fb5556c3b5fdb3bff762a42f16c21a7fa65d801,PMC,MMP-independent role of TIMP-1 at the blood brain barrier during viral encephalomyelitis,http://dx.doi.org/10.1042/AN20130033,PMC3840398,24156369,CC BY,"Infection of the CNS (central nervous system) with a sublethal neurotropic coronavirus (JHMV) induces a vigorous inflammatory response. CD4(+) and CD8(+) T cells are essential to control infectious virus but at the cost of tissue damage. An enigma in understanding the contribution of T cell subsets in pathogenesis resides in their distinct migration pattern across the BBB (blood brain barrier). CD4(+) T cells transiently accumulate within the perivascular space, whereas CD8(+) T cells migrate directly into the CNS parenchyma. As MMPs (matrix metalloproteinases) facilitate migration across the glia limitans, specific expression of the TIMP (tissue inhibitor of MMPs)-1 by CD4(+) T cells present in the perivascular cuffs suggested that TIMP-1 is responsible for stalling CD4(+) T cell migration into the CNS parenchyma. Using TIMP-1 deficient mice, the present data demonstrate an increase rather than a decrease in CD4(+) T cell accumulation within the perivascular space during JHMV infection. Whereas virus control was not affected by perivascular retention of CD4(+) T cells, disease severity was decreased and associated with reduced IFNγ (interferon γ) production. Moreover, decreased CD4(+) T cell recruitment into the CNS parenchyma of TIMP-1 deficient mice was not associated with impaired T cell recruiting chemokines or MMP expression, and no compensation by other TIMP molecules was identified. These data suggest an MMP-independent role of TIMP-1 in regulating CD4(+) T cell access into the CNS parenchyma during acute JHMV encephalitis.",2013 Nov 26,"['Savarin, Carine', 'Bergmann, Cornelia\xa0C.', 'Hinton, David\xa0R.', 'Stohlman, Stephen\xa0A.']",ASN Neuro,,,True
377bace754b08919a4139b9f1070f8ab422f90bc,PMC,Pandemic influenza viruses: time to recognize our inability to predict the unpredictable and stop dangerous gain-of-function experiments,http://dx.doi.org/10.1002/emmm.201303475,PMC3840482,24186378,CC BY,,2013 Nov 24,"Wain-Hobson, Simon",EMBO Mol Med,,,True
92911175d25c9f4bce7ace3050a4ddea1f5105eb,PMC,Efficacy of a Carrageenan nasal spray in patients with common cold: a randomized controlled trial,http://dx.doi.org/10.1186/1465-9921-14-124,PMC3840586,24219370,CC BY,"BACKGROUND: The common cold is the most widespread viral infection in humans. Iota-carrageenan has previously shown antiviral effectiveness against cold viruses in clinical trials. This study investigated the efficacy of a carrageenan-containing nasal spray on the duration of the common cold and nasal fluid viral load in adult patients. METHODS: In a randomized, double-blind, placebo-controlled trial, 211 patients suffering from early symptoms of the common cold were treated for seven days. Application was performed three times daily with either a carrageenan-supplemented nasal spray or saline solution as placebo with an overall observation period of 21 days. The primary endpoint was the duration of disease defined as the time until the last day with symptoms followed by all other days in the study period without symptoms. During the study, but prior unblinding, the definition of disease duration was adapted from the original protocol that defines disease duration as the time period of symptoms followed by 48 hours without symptoms. RESULTS: In patients showing a laboratory-confirmed cold virus infection and adherence to the protocol, alleviation of symptoms was 2.1 days faster in the carrageenan group in comparison to placebo (p = 0.037). The primary endpoint that had been prespecified but was changed before unblinding was not met. Viral titers in nasal fluids showed a significantly greater decrease in carrageenan patients in the intention-to-treat population (p = 0.024) and in the per protocol population (p = 0.018) between days 1 and 3/4. CONCLUSIONS: In adults with common cold virus infections, direct local administration of carrageenan with nasal sprays reduced the duration of cold symptoms. A significant reduction of viral load in the nasal wash fluids of patients confirmed similar findings from earlier trials in children and adults. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80148028",2013 Nov 13,"['Ludwig, Martin', 'Enzenhofer, Elisabeth', 'Schneider, Sven', 'Rauch, Margit', 'Bodenteich, Angelika', 'Neumann, Kurt', 'Prieschl-Grassauer, Eva', 'Grassauer, Andreas', 'Lion, Thomas', 'Mueller, Christian A']",Respir Res,,,True
0b227d1996bc5dfd895b43f6c6e2449c58252c67,PMC,Insufficient preparedness of primary care practices for pandemic influenza and the effect of a preparedness plan in Japan: a prefecture-wide cross-sectional study,http://dx.doi.org/10.1186/1471-2296-14-174,PMC3840630,24252688,CC BY,"BACKGROUND: Cases of emerging infectious diseases, including H5N1 influenza, H7N9 influenza, and Middle East Respiratory Syndrome, have been reported in recent years, and the threat of pandemic outbreaks persists. In Japan, primary care is the frontline against emerging infectious diseases in communities. Although the importance of pandemic preparedness in primary care has been highlighted previously, few studies have thus far investigated the preparedness among primary care practices (PCPs) or differences in the preparedness of different institutional settings. We examined PCP preparedness and response to the 2009 influenza pandemic in Japan, and explored the role of a pandemic preparedness plan during the pandemic. METHODS: We used a survey questionnaire to assess how well individual PCPs in Okinawa, Japan, were prepared for the 2009 influenza pandemic. The questionnaire was mailed to all eligible PCPs (N = 465) in Okinawa, regardless of their institutional setting. In addition, we assessed the differences in the preparedness of clinics and hospitals and determined whether the national preparedness plan affected individual preparedness and response. Data were analyzed using descriptive and logistic regression analyses. RESULTS: A total of 174 (37.4%) PCPs responded to our survey. In general, high-level personal protective equipment (PPE) such as N95 masks (45.4%), gowns (30.5%), and eye protection (21.3%) was stocked at a low rate. Clinic-based PCPs were significantly less prepared than hospital-based PCPs to provide N95 masks (OR 0.34), gowns (OR 0.15), and eye protection (OR 0.18). In addition, only 32.8% of PCPs adopted an adequate business continuity plan (BCP). After controlling for institutional setting, reading the national preparedness plan was significantly associated with establishment of a BCP (OR 5.86), and with knowledge of how to transfer a swab specimen to a local medical laboratory (OR 5.60). CONCLUSIONS: With regard to PPE availability, PCPs (especially clinic-based PCPs) were not adequately prepared for the influenza pandemic. Awareness of the national pandemic preparedness plan is likely to promote prefecture-wide implementation of BCPs and surveillance activity.",2013 Nov 19,"['Tomizuka, Taro', 'Kanatani, Yasuhiro', 'Kawahara, Kazuo']",BMC Fam Pract,,,True
2d51e2d2cbb76670bc27af8af326084f00f235db,PMC,Insufficient preparedness of primary care practices for pandemic influenza and the effect of a preparedness plan in Japan: a prefecture-wide cross-sectional study,http://dx.doi.org/10.1186/1471-2296-14-174,PMC3840630,24252688,CC BY,"BACKGROUND: Cases of emerging infectious diseases, including H5N1 influenza, H7N9 influenza, and Middle East Respiratory Syndrome, have been reported in recent years, and the threat of pandemic outbreaks persists. In Japan, primary care is the frontline against emerging infectious diseases in communities. Although the importance of pandemic preparedness in primary care has been highlighted previously, few studies have thus far investigated the preparedness among primary care practices (PCPs) or differences in the preparedness of different institutional settings. We examined PCP preparedness and response to the 2009 influenza pandemic in Japan, and explored the role of a pandemic preparedness plan during the pandemic. METHODS: We used a survey questionnaire to assess how well individual PCPs in Okinawa, Japan, were prepared for the 2009 influenza pandemic. The questionnaire was mailed to all eligible PCPs (N = 465) in Okinawa, regardless of their institutional setting. In addition, we assessed the differences in the preparedness of clinics and hospitals and determined whether the national preparedness plan affected individual preparedness and response. Data were analyzed using descriptive and logistic regression analyses. RESULTS: A total of 174 (37.4%) PCPs responded to our survey. In general, high-level personal protective equipment (PPE) such as N95 masks (45.4%), gowns (30.5%), and eye protection (21.3%) was stocked at a low rate. Clinic-based PCPs were significantly less prepared than hospital-based PCPs to provide N95 masks (OR 0.34), gowns (OR 0.15), and eye protection (OR 0.18). In addition, only 32.8% of PCPs adopted an adequate business continuity plan (BCP). After controlling for institutional setting, reading the national preparedness plan was significantly associated with establishment of a BCP (OR 5.86), and with knowledge of how to transfer a swab specimen to a local medical laboratory (OR 5.60). CONCLUSIONS: With regard to PPE availability, PCPs (especially clinic-based PCPs) were not adequately prepared for the influenza pandemic. Awareness of the national pandemic preparedness plan is likely to promote prefecture-wide implementation of BCPs and surveillance activity.",2013 Nov 19,"['Tomizuka, Taro', 'Kanatani, Yasuhiro', 'Kawahara, Kazuo']",BMC Fam Pract,,,False
ef38ed2f4cc96e16ce011623cc5d15d2d8ca58c3,PMC,Efficient generation of recombinant RNA viruses using targeted recombination-mediated mutagenesis of bacterial artificial chromosomes containing full-length cDNA,http://dx.doi.org/10.1186/1471-2164-14-819,PMC3840674,24262008,CC BY,"BACKGROUND: Infectious cDNA clones are a prerequisite for directed genetic manipulation of RNA viruses. Here, a strategy to facilitate manipulation and rescue of classical swine fever viruses (CSFVs) from full-length cDNAs present within bacterial artificial chromosomes (BACs) is described. This strategy allows manipulation of viral cDNA by targeted recombination-mediated mutagenesis within bacteria. RESULTS: A new CSFV-BAC (pBeloR26) derived from the Riems vaccine strain has been constructed and subsequently modified in the E2 coding sequence, using the targeted recombination strategy to enable rescue of chimeric pestiviruses (vR26_E2gif and vR26_TAV) with potential as new marker vaccine candidates. Sequencing of the BACs revealed a high genetic stability during passages within bacteria. The complete genome sequences of rescued viruses, after extensive passages in mammalian cells showed that modifications in the E2 protein coding sequence were stably maintained. A single amino acid substitution (D3431G) in the RNA dependent RNA polymerase was observed in the rescued viruses vR26_E2gif and vR26, which was reversion to the parental Riems sequence. CONCLUSIONS: These results show that targeted recombination-mediated mutagenesis provides a powerful tool for expediting the construction of novel RNA genomes and should be applicable to the manipulation of other RNA viruses.",2013 Nov 22,"['Rasmussen, Thomas Bruun', 'Risager, Peter Christian', 'Fahnøe, Ulrik', 'Friis, Martin Barfred', 'Belsham, Graham J', 'Höper, Dirk', 'Reimann, Ilona', 'Beer, Martin']",BMC Genomics,,,True
b3e679d6e37ba367e165971515663ecd71ea522c,PMC,Synonymous Codon Usage in TTSuV2: Analysis and Comparison with TTSuV1,http://dx.doi.org/10.1371/journal.pone.0081469,PMC3841265,24303050,CC BY,"Two species of the DNA virus Torque teno sus virus (TTSuV), TTSuV1 and TTSuV2, have become widely distributed in pig-farming countries in recent years. In this study, we performed a comprehensive analysis of synonymous codon usage bias in 41 available TTSuV2 coding sequences (CDS), and compared the codon usage patterns of TTSuV2 and TTSuV1. TTSuV codon usage patterns were found to be phylogenetically conserved. Values for the effective number of codons (ENC) indicated that the overall extent of codon usage bias in both TTSuV2 and TTSuV1 was not significant, the most frequently occurring codons had an A or C at the third codon position. Correspondence analysis (COA) was performed and TTSuV2 and TTSuV1 sequences were located in different quadrants of the first two major axes. A plot of the ENC revealed that compositional constraint was the major factor determining the codon usage bias for TTSuV2. In addition, hierarchical cluster analysis of 41 TTSuV2 isolates based on relative synonymous codon usage (RSCU) values suggested that there was no association between geographic distribution and codon bias of TTSuV2 sequences. Finally, the comparison of RSCU for TTSuV2, TTSuV1 and the corresponding host sequence indicated that the codon usage pattern of TTSuV2 was similar to that of TTSuV1. However the similarity was low for each virus and its host. These conclusions provide important insight into the synonymous codon usage pattern of TTSuV2, as well as better understangding of the molecular evolution of TTSuV2 genomes.",2013 Nov 26,"['Zhang, Zhicheng', 'Dai, Wei', 'Dai, Dingzhen']",PLoS One,,,True
39aba27d479a1340c398f332053951fb33606dcd,PMC,Positive Evolutionary Selection On the RIG-I-Like Receptor Genes in Mammals,http://dx.doi.org/10.1371/journal.pone.0081864,PMC3842351,24312370,CC BY,"The mammalian RIG-I-like receptors, RIG-I, MDA5 and LGP2, are a family of DExD/H box RNA helicases responsible for the cytoplasmic detection of viral RNA. These receptors detect a variety of RNA viruses, or DNA viruses that express unusual RNA species, many of which are responsible for a great number of severe and lethal diseases. Host innate sentinel proteins involved in pathogen recognition must rapidly evolve in a dynamic arms race with pathogens, and thus are subjected to long-term positive selection pressures to avoid potential infections. Using six codon-based Maximum Likelihood methods, we were able to identify specific codons under positive selection in each of these three genes. The highest number of positively selected codons was detected in MDA5, but a great percentage of these codons were located outside of the currently defined protein domains for MDA5, which likely reflects the imposition of both functional and structural constraints. Additionally, our results support LGP2 as being the least prone to evolutionary change, since the lowest number of codons under selection was observed for this gene. On the other hand, the preponderance of positively selected codons for RIG-I were detected in known protein functional domains, suggesting that pressure has been imposed by the vast number of viruses that are recognized by this RNA helicase. Furthermore, the RIG-I repressor domain, the region responsible for recognizing and binding to its RNA substrates, exhibited the strongest evidence of selective pressures. Branch-site analyses were performed and several species branches on the three receptor gene trees showed evidence of episodic positive selection. In conclusion, by looking for evidence of positive evolutionary selection on mammalian RIG-I-like receptor genes, we propose that a multitude of viruses have crafted the receptors biological function in host defense, specifically for the RIG-I gene, contributing to the innate species-specific resistance/susceptibility to diverse viral pathogens.",2013 Nov 27,"['Lemos de Matos, Ana', 'McFadden, Grant', 'Esteves, Pedro J.']",PLoS One,,,True
8d75437a3933156f016f8b3ef139d206c63f9bec,PMC,Positive Evolutionary Selection On the RIG-I-Like Receptor Genes in Mammals,http://dx.doi.org/10.1371/journal.pone.0081864,PMC3842351,24312370,CC BY,"The mammalian RIG-I-like receptors, RIG-I, MDA5 and LGP2, are a family of DExD/H box RNA helicases responsible for the cytoplasmic detection of viral RNA. These receptors detect a variety of RNA viruses, or DNA viruses that express unusual RNA species, many of which are responsible for a great number of severe and lethal diseases. Host innate sentinel proteins involved in pathogen recognition must rapidly evolve in a dynamic arms race with pathogens, and thus are subjected to long-term positive selection pressures to avoid potential infections. Using six codon-based Maximum Likelihood methods, we were able to identify specific codons under positive selection in each of these three genes. The highest number of positively selected codons was detected in MDA5, but a great percentage of these codons were located outside of the currently defined protein domains for MDA5, which likely reflects the imposition of both functional and structural constraints. Additionally, our results support LGP2 as being the least prone to evolutionary change, since the lowest number of codons under selection was observed for this gene. On the other hand, the preponderance of positively selected codons for RIG-I were detected in known protein functional domains, suggesting that pressure has been imposed by the vast number of viruses that are recognized by this RNA helicase. Furthermore, the RIG-I repressor domain, the region responsible for recognizing and binding to its RNA substrates, exhibited the strongest evidence of selective pressures. Branch-site analyses were performed and several species branches on the three receptor gene trees showed evidence of episodic positive selection. In conclusion, by looking for evidence of positive evolutionary selection on mammalian RIG-I-like receptor genes, we propose that a multitude of viruses have crafted the receptors biological function in host defense, specifically for the RIG-I gene, contributing to the innate species-specific resistance/susceptibility to diverse viral pathogens.",2013 Nov 27,"['Lemos de Matos, Ana', 'McFadden, Grant', 'Esteves, Pedro J.']",PLoS One,,,False
c4a6222c0b432f6757267c5c6db630859f0bcadb,PMC,Positive Evolutionary Selection On the RIG-I-Like Receptor Genes in Mammals,http://dx.doi.org/10.1371/journal.pone.0081864,PMC3842351,24312370,CC BY,"The mammalian RIG-I-like receptors, RIG-I, MDA5 and LGP2, are a family of DExD/H box RNA helicases responsible for the cytoplasmic detection of viral RNA. These receptors detect a variety of RNA viruses, or DNA viruses that express unusual RNA species, many of which are responsible for a great number of severe and lethal diseases. Host innate sentinel proteins involved in pathogen recognition must rapidly evolve in a dynamic arms race with pathogens, and thus are subjected to long-term positive selection pressures to avoid potential infections. Using six codon-based Maximum Likelihood methods, we were able to identify specific codons under positive selection in each of these three genes. The highest number of positively selected codons was detected in MDA5, but a great percentage of these codons were located outside of the currently defined protein domains for MDA5, which likely reflects the imposition of both functional and structural constraints. Additionally, our results support LGP2 as being the least prone to evolutionary change, since the lowest number of codons under selection was observed for this gene. On the other hand, the preponderance of positively selected codons for RIG-I were detected in known protein functional domains, suggesting that pressure has been imposed by the vast number of viruses that are recognized by this RNA helicase. Furthermore, the RIG-I repressor domain, the region responsible for recognizing and binding to its RNA substrates, exhibited the strongest evidence of selective pressures. Branch-site analyses were performed and several species branches on the three receptor gene trees showed evidence of episodic positive selection. In conclusion, by looking for evidence of positive evolutionary selection on mammalian RIG-I-like receptor genes, we propose that a multitude of viruses have crafted the receptors biological function in host defense, specifically for the RIG-I gene, contributing to the innate species-specific resistance/susceptibility to diverse viral pathogens.",2013 Nov 27,"['Lemos de Matos, Ana', 'McFadden, Grant', 'Esteves, Pedro J.']",PLoS One,,,False
1c5dd9051932934f62921f37a1d2a3d739fd4a95,PMC,Positive Evolutionary Selection On the RIG-I-Like Receptor Genes in Mammals,http://dx.doi.org/10.1371/journal.pone.0081864,PMC3842351,24312370,CC BY,"The mammalian RIG-I-like receptors, RIG-I, MDA5 and LGP2, are a family of DExD/H box RNA helicases responsible for the cytoplasmic detection of viral RNA. These receptors detect a variety of RNA viruses, or DNA viruses that express unusual RNA species, many of which are responsible for a great number of severe and lethal diseases. Host innate sentinel proteins involved in pathogen recognition must rapidly evolve in a dynamic arms race with pathogens, and thus are subjected to long-term positive selection pressures to avoid potential infections. Using six codon-based Maximum Likelihood methods, we were able to identify specific codons under positive selection in each of these three genes. The highest number of positively selected codons was detected in MDA5, but a great percentage of these codons were located outside of the currently defined protein domains for MDA5, which likely reflects the imposition of both functional and structural constraints. Additionally, our results support LGP2 as being the least prone to evolutionary change, since the lowest number of codons under selection was observed for this gene. On the other hand, the preponderance of positively selected codons for RIG-I were detected in known protein functional domains, suggesting that pressure has been imposed by the vast number of viruses that are recognized by this RNA helicase. Furthermore, the RIG-I repressor domain, the region responsible for recognizing and binding to its RNA substrates, exhibited the strongest evidence of selective pressures. Branch-site analyses were performed and several species branches on the three receptor gene trees showed evidence of episodic positive selection. In conclusion, by looking for evidence of positive evolutionary selection on mammalian RIG-I-like receptor genes, we propose that a multitude of viruses have crafted the receptors biological function in host defense, specifically for the RIG-I gene, contributing to the innate species-specific resistance/susceptibility to diverse viral pathogens.",2013 Nov 27,"['Lemos de Matos, Ana', 'McFadden, Grant', 'Esteves, Pedro J.']",PLoS One,,,False
c7d8100f9f9f799f495a0458c8f23dcc7bcec3ec,PMC,Efficacy of cineole in patients suffering from acute bronchitis: a placebo-controlled double-blind trial,http://dx.doi.org/10.1186/1745-9974-9-25,PMC3842692,24261680,CC BY,"OBJECTIVE: Cineole has mucolytic, bronchodilating and anti-inflammatory properties and reduces the exacerbation rate in patients suffering from COPD, as well as ameliorates symptoms in patients suffering from asthma and rhinosinusitis. Based on these effects, we therefore postulated the hypothesis that patients with acute bronchitis would also benefit from therapy with Cineole. METHODS: As part of a double-blind, placebo-controlled, multi-center-study, a total of 242 patients with confirmed acute bronchitis was randomly selected to participate. Over a period of 10 days, all patients were administered 3 x 200 mg of Cineole, or a respective placebo, per day. The primary outcome measure was a Bronchitis Sum Score, which summarises the relevant symptoms of acute bronchitis. RESULTS: After 4 days of treatment it was notable, that the patient group treated with Cineole, showed significantly more improvements of the bronchitis-sum-score than those of the placebo group (p = 0.0383). The statistical significant difference of the individual outcome measures was especially underlined by the frequency of cough fits by p = 0.0001 after 4 days. CONCLUSIONS: The effects of Cineole in the treatment of acute bronchitis were clearly measurable and could be proven after a treatment period of merely 4 days. This study corroborates the fact that Cineole actively and significantly reduces cough frequency after four days. Therefore it has been shown to have a great socioeconomic impact. TRIAL REGISTRATION: ISRCTN: ISRCTN37784439",2013 Nov 21,"['Fischer, Juergen', 'Dethlefsen, Uwe']",Cough,,,True
378082edc2f3e85e6cc8941c81030a70c65c7f8f,PMC,Dendritic Cell-Specific Delivery of Flt3L by Coronavirus Vectors Secures Induction of Therapeutic Antitumor Immunity,http://dx.doi.org/10.1371/journal.pone.0081442,PMC3842931,24312302,CC BY,"Efficacy of antitumor vaccination depends to a large extent on antigen targeting to dendritic cells (DCs). Here, we assessed antitumor immunity induced by attenuated coronavirus vectors which exclusively target DCs in vivo and express either lymphocyte- or DC-activating cytokines in combination with a GFP-tagged model antigen. Tracking of in vivo transduced DCs revealed that vectors encoding for Fms-like tyrosine kinase 3 ligand (Flt3L) exhibited a higher capacity to induce DC maturation compared to vectors delivering IL-2 or IL-15. Moreover, Flt3L vectors more efficiently induced tumor-specific CD8(+) T cells, expanded the epitope repertoire, and provided both prophylactic and therapeutic tumor immunity. In contrast, IL-2- or IL-15-encoding vectors showed a substantially lower efficacy in CD8(+) T cell priming and failed to protect the host once tumors had been established. Thus, specific in vivo targeting of DCs with coronavirus vectors in conjunction with appropriate conditioning of the microenvironment through Flt3L represents an efficient strategy for the generation of therapeutic antitumor immunity.",2013 Nov 28,"['Perez-Shibayama, Christian', 'Gil-Cruz, Cristina', 'Nussbacher, Monika', 'Allgäuer, Eva', 'Cervantes-Barragan, Luisa', 'Züst, Roland', 'Ludewig, Burkhard']",PLoS One,,,True
5ff6f535016d7b46687474786efd07db9c19ce8e,PMC,Investigation of serum protein profiles in scrapie infected sheep by means of SELDI-TOF-MS and multivariate data analysis,http://dx.doi.org/10.1186/1756-0500-6-466,PMC3843553,24229425,CC BY,"BACKGROUND: Classical scrapie in sheep is a fatal neurodegenerative disease associated with the conversion PrP(C) to PrP(Sc). Much is known about genetic susceptibility, uptake and dissemination of PrP(Sc) in the body, but many aspects of prion diseases are still unknown. Different proteomic techniques have been used during the last decade to investigate differences in protein profiles between affected animals and healthy controls. We have investigated the protein profiles in serum of sheep with scrapie and healthy controls by SELDI-TOF-MS and LC-MS/MS. Latent Variable methods such as Principal Component Analysis, Partial Least Squares-Discriminant Analysis and Target Projection methods were used to describe the MS data. RESULTS: The serum proteomic profiles showed variable differences between the groups both throughout the incubation period and at the clinical end stage of scrapie. At the end stage, the target projection model separated the two groups with a sensitivity of 97.8%, and serum amyloid A was identified as one of the protein peaks that differed significantly between the groups. CONCLUSIONS: At the clinical end stage of classical scrapie, ten SELDI peaks significantly discriminated the scrapie group from the healthy controls. During the non-clinical incubation period, individual SELDI peaks were differently expressed between the groups at different time points. Investigations of differences in -omic profiles can contribute to new insights into the underlying disease processes and pathways, and advance our understanding of prion diseases, but comparison and validation across laboratories is difficult and challenging.",2013 Nov 14,"['Meling, Siv', 'Kvalheim, Olav M', 'Arneberg, Reidar', 'Bårdsen, Kjetil', 'Hjelle, Anne', 'Ulvund, Martha J']",BMC Res Notes,,,True
9976bf51302bf33a5384a30c73231d4077c63ffe,PMC,"Genotyping and pathobiologic characterization of canine parvovirus circulating in Nanjing, China",http://dx.doi.org/10.1186/1743-422X-10-272,PMC3844316,23988202,CC BY,"BACKGROUND: Canine parvovirus (CPV) is an important pathogen that causes acute enteric disease in dogs. It has mutated and spread throughout the world in dog populations. We provide an update on the molecular characterization of CPV that circulated in Nanjing, a provincial capital in China between 2009 and 2012. RESULTS: Seventy rectal swab samples were collected from the dogs diagnosed with CPV infection in 8 animal hospitals of Nanjing. Sequence analysis of VP2 genes of 31 samples revealed that 29 viral strains belonged to CPV-2a subtype, while other two strains were classified into CPV-2b. To investigate the pathogenicity of the prevalent virus, we isolated CPV-2a and performed the animal experiment. Nine beagles were inoculated with 10(5.86) of 50% tissue culture infectious doses (TCID(50)) of the virus. All the experimentally infected beagles exhibited mild to moderate mucoid or watery diarrhea on day 4 post-infection (p.i.). On day 9 p.i., characteristic histopathological lesions were clearly observed in multiple organs of infected dogs, including liver, spleen, kidney, brain and all segments of the small and large intestines, while viral DNA and antigen staining could be detected in the sampled tissues. It is notable that canine parvovirus was isolated in one from two brain samples processed. CONCLUSION: Our results indicated that CPV-2a is the predominant subtype in Nanjing of China. And this virus caused extensive lesions in a variety of tissues, including the brain.",2013 Aug 29,"['Zhao, Yanbing', 'Lin, Yan', 'Zeng, Xujian', 'Lu, Chengping', 'Hou, Jiafa']",Virol J,,,True
fa93cc1d684bce742748b879031332537855f5ec,PMC,The Effect of Postoperative Corticosteroid Administration on Free Vascularized Fibular Grafting for Treating Osteonecrosis of the Femoral Head,http://dx.doi.org/10.1155/2013/708014,PMC3845513,24324377,CC BY,"Free vascularized fibular grafting (FVFG) has been reported to be an effective method of treating osteonecrosis of the femoral head (ONFH). This study evaluated whether postoperative maintenance doses of corticosteroids had an adverse effect on FVFG outcomes in patients with corticosteroid-induced ONFH. We retrospectively reviewed the records of 39 patients (67 hips) who had received maintenance doses of corticosteroids following FVFG. This group was matched to a group of patients who had not received corticosteroids treatment after operation. The mean follow-up duration was 5.4 years for the postoperative corticosteroid administration group (PCA group) and 5.0 years for the control group. At the latest follow-up, the average increase in Harris hip score was 11.1 ± 8.7 points for all hips in the PCA group and 12.6 ± 7.4 points for all hips in the control group (P > 0.05). In the PCA group, through radiographic evaluation, 49 hips were improved, 10 hips appeared unchanged, and 8 hips appeared worse. In the control group, 47 hips were improved, 13 hips appeared unchanged, and 7 hips appeared worse. The results suggested that postoperative maintenance doses of corticosteroids do not have an adverse effect on FVFG outcomes in patients with corticosteroid-induced ONFH.",2013 Nov 12,"['Ding, Hao', 'Chen, Sheng-Bao', 'Lin, Sen', 'Gao, You-Shui', 'Zhang, Chang-Qing']",ScientificWorldJournal,,,True
70542f1f1a2ced1e26658f62372e882da4c2b366,PMC,Effectiveness of cough etiquette maneuvers in disrupting the chain of transmission of infectious respiratory diseases,http://dx.doi.org/10.1186/1471-2458-13-811,PMC3846148,24010919,CC BY,"BACKGROUND: The effectiveness of recommended measures, such as “cover your mouth when coughing”, in disrupting the chain of transmission of infectious respiratory diseases (IRD) has been questioned. The objective of the current study was to determine the effectiveness of simple primary respiratory hygiene/cough etiquette maneuvers in blocking droplets expelled as aerosol during coughing. METHOD: In this study, 31 healthy non-smokers performed cough etiquette maneuvers in an effort to cover their voluntarily elicited best effort coughs in an open bench format. A laser diffraction system was used to obtain accurate, non-invasive, quantitative, real time measurements of the size and number of droplets emitted during the assessed cough etiquette maneuvers. RESULTS: Recommended cough etiquette maneuvers did not block the release and dispersion of a variety of different diameter droplets to the surrounding environment. Droplets smaller than one-micron size dominate the total number of droplets leaked when practicing assessed maneuvers. CONCLUSIONS: All the assessed cough etiquette maneuvers, performed as recommended, do not block droplets expelled as aerosol when coughing. This aerosol can penetrate profound levels of the respiratory system. Practicing these assessed primary respiratory hygiene/cough etiquette maneuvers would still permit direct, indirect, and/or airborne transmission and spread of IRD, such as influenza and Tuberculosis. All the assessed cough etiquette maneuvers, as recommended, do not fully interrupt the chain of transmission of IRD. This knowledge urges us all to critically review recommended CE and to search for new evidence-based procedures that effectively disrupt the transmission of respiratory pathogens. Interrupting the chain of transmission of IRD will optimize the protection of first responders, paramedics, nurses, and doctors working in triage sites, emergency rooms, intensive care units, and the general public against cough-droplet-spread diseases.",2013 Sep 8,"['Zayas, Gustavo', 'Chiang, Ming C', 'Wong, Eric', 'MacDonald, Fred', 'Lange, Carlos F', 'Senthilselvan, Ambikaipakan', 'King, Malcolm']",BMC Public Health,,,True
6f0572cc1fa39ecc775cf576db694638a7fb9bc1,PMC,Bacterial artificial chromosome derived simian varicella virus is pathogenic in vivo,http://dx.doi.org/10.1186/1743-422X-10-278,PMC3846606,24010815,CC BY,"BACKGROUND: Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus that infects humans and results in chickenpox and herpes zoster. A number of VZV genes remain functionally uncharacterized and since VZV is an obligate human pathogen, rigorous evaluation of VZV mutants in vivo remains challenging. Simian varicella virus (SVV) is homologous to VZV and SVV infection of rhesus macaques (RM) closely mimics VZV infection of humans. Recently the SVV genome was cloned as a bacterial artificial chromosome (BAC) and BAC-derived SVV displayed similar replication kinetics as wild-type (WT) SVV in vitro. METHODS: RMs were infected with BAC-derived SVV or WT SVV at 4x10(5) PFU intrabronchially (N=8, 4 per group, sex and age matched). We collected whole blood (PBMC) and bronchoalveolar lavage (BAL) at various days post-infection (dpi) and sensory ganglia during latent infection (>84 dpi) at necropsy and compared disease progression, viral replication, immune response and the establishment of latency. RESULTS: Viral replication kinetics and magnitude in bronchoalveolar lavage cells and whole blood as well as rash severity and duration were similar in RMs infected with SVV BAC or WT SVV. Moreover, SVV-specific B and T cell responses were comparable between BAC and WT-infected animals. Lastly, we measured viral DNA in sensory ganglia from both cohorts of infected RMs during latent infection. CONCLUSIONS: SVV BAC is as pathogenic and immunogenic as WT SVV in vivo. Thus, the SVV BAC genetic system combined with the rhesus macaque animal model can further our understanding of viral ORFs important for VZV pathogenesis and the development of second-generation vaccines.",2013 Sep 8,"['Meyer, Christine', 'Dewane, Jesse', 'Haberthur, Kristen', 'Engelmann, Flora', 'Arnold, Nicole', 'Gray, Wayne', 'Messaoudi, Ilhem']",Virol J,,,True
38eee3781e1192464696b9a1164834259214cde9,PMC,Calf-Level Factors Associated with Bovine Neonatal Pancytopenia – A Multi-Country Case-Control Study,http://dx.doi.org/10.1371/journal.pone.0080619,PMC3846664,24312485,CC BY,"Bovine neonatal pancytopenia (BNP), a high fatality condition causing haemorrhages in calves aged less than 4 weeks, was first reported in 2007 in Germany and subsequently observed at low incidence in other European countries and New Zealand. A multi-country matched case-control study was conducted in 2011 to identify calf-level risk factors for BNP. 405 BNP cases were recruited from 330 farms in Belgium, France, Germany and the Netherlands by laboratory confirmation of farmer-reported cases. Up to four calves of similar age from the same farm were selected as controls (1154 calves). Risk factor data were collected by questionnaire. Multivariable modelling using conditional logistic regression indicated that PregSure®BVD (PregSure, Pfizer Animal Health) vaccination of the dam was strongly associated with BNP cases (adjusted matched Odds Ratio - amOR 17.8 first lactation dams; 95% confidence interval – ci 2.4, 134.4; p = 0.005), and second or more lactation PregSure-vaccinated dams were more likely to have a case than first lactation vaccinated dams (amOR 2.2 second lactation; ci 1.1, 4.3; p = 0.024; amOR 5.3 third or more lactation; ci 2.9, 9.8; p = <0.001). Feeding colostrum from other cows was strongly associated with BNP if the dam was not PregSure-vaccinated (amOR 30.5; ci 2.1, 440.5; p = 0.012), but the effect was less if the dam was PregSure-vaccinated (amOR 2.1; ci 1.1, 4.0; p = 0.024). Feeding exclusively dam’s milk was a higher risk than other types of milk (amOR 3.4; ci 1.6, 7.5; p = 0.002). The population attributable fractions were 0.84 (ci 0.68, 0.92) for PregSure vaccination, 0.13 (ci 0.06, 0.19) for feeding other cows’ colostrum, and 0.15 (ci 0.08, 0.22) for feeding dam’s milk. No other calf-level factors were identified, suggesting that there are other important factors that are outside the scope of this study, such as genetics, which explain why BNP develops in some PregSure-colostrum-exposed calves but not in others.",2013 Dec 2,"['Jones, Bryony A.', 'Sauter-Louis, Carola', 'Henning, Joerg', 'Stoll, Alexander', 'Nielen, Mirjam', 'Van Schaik, Gerdien', 'Smolenaars, Anja', 'Schouten, Matthijs', 'den Uijl, Ingrid', 'Fourichon, Christine', 'Guatteo, Raphael', 'Madouasse, Aurélien', 'Nusinovici, Simon', 'Deprez, Piet', 'De Vliegher, Sarne', 'Laureyns, Jozef', 'Booth, Richard', 'Cardwell, Jackie M.', 'Pfeiffer, Dirk U.']",PLoS One,,,True
5c3f5dde0537e3072d046990501a4e71471d9ddc,PMC,DC-SIGN gene promoter variants and IVIG treatment response in Kawasaki disease,http://dx.doi.org/10.1186/1546-0096-11-32,PMC3847673,24006904,CC BY,"BACKGROUND: Genetic variants in the inhibiting FcγRIIB mediate anti-inflammatory responses and influence IVIG refractoriness (IVIG-R). However, these variants are rare in Asian and Hispanic populations so other genes in the pathway could be potentially involved. IVIG is ineffective in mice lacking SIGN-R1, a related molecule to human DC-SIGN. Further, DC-SIGN is a known receptor for sialylated Fc, the component responsible for the anti-inflammatory action of IVIG. Thus, we hypothesized that DC-SIGN would also be involved in the pathway of IVIG response in Kawasaki Disease (KD) patients. FINDINGS: A case-control approach was performed to examine the differential distribution of five single nucleotide polymorphisms (SNPs) in DC-SIGN promoter with IVIG-R among White (158 vs. 62), Asian (64 vs. 12) and Hispanic (55 vs. 20) KD patients. Distinct differences in allele frequency distributions of several variants in the DC-SIGN promoter were observed in the three ethnic groups. Further, Asians with the major allele “A” in rs2287886 were more likely (OR = 1.76, p = 0.04) to be IVIG non-responder, but this allele is a minor allele in other two ethnic groups, where the association was not apparent. CONCLUSIONS: DC-SIGN can potentially complement the role of FcγRIIB in the anti-inflammatory cascade involved in the IVIG response mechanism.",2013 Sep 5,"['Portman, Michael A', 'Wiener, Howard W', 'Silva, Miriam', 'Shendre, Aditi', 'Shrestha, Sadeep']",Pediatr Rheumatol Online J,,,True
2a79ac3a49714d75cfc75c28df0a4e33d9362969,PMC,Respiratory virus surveillance in hospitalised pneumonia patients on the Thailand-Myanmar border,http://dx.doi.org/10.1186/1471-2334-13-434,PMC3847692,24498873,CC BY,"BACKGROUND: Pneumonia is a significant cause of morbidity and mortality in the developing world. Viruses contribute significantly to pneumonia burden, although data for low-income and tropical countries are scarce. The aim of this laboratory-enhanced, hospital-based surveillance was to characterise the epidemiology of respiratory virus infections among refugees living on the Thailand-Myanmar border. METHODS: Maela camp provides shelter for ~45,000 refugees. Inside the camp, a humanitarian organisation provides free hospital care in a 158-bed inpatient department (IPD). Between 1st April 2009 and 30th September 2011, all patients admitted to the IPD with a clinical diagnosis of pneumonia were invited to participate. Clinical symptoms and signs were recorded and a nasopharyngeal aspirate (NPA) collected. NPAs were tested for adenoviruses, human metapneumovirus (hMPV), influenza A & B, and RSV by PCR. RESULTS: Seven hundred eight patient episodes (698 patients) diagnosed as pneumonia during the enhanced surveillance period were included in this analysis. The median patient age was 1 year (range: < 1-70), and 90.4% were aged < 5 years. At least one virus was detected in 53.7% (380/708) of episodes. Virus detection was more common in children aged < 5 years old (<1 year: OR 2.0, 95% CI 1.2-3.4, p = 0.01; 1-4 years: OR 1.4, 95% CI 0.8-2.3, p = 0.2). RSV was detected in 176/708 (24.9%); an adenovirus in 133/708 (18.8%); an influenza virus in 68/708 (9.6%); and hMPV in 33/708 (4.7%). Twenty-eight episodes of multiple viral infections were identified, most commonly adenovirus plus another virus. RSV was more likely to be detected in children <5 years (OR 12.3, 95% CI 3.0-50.8, p = 0.001) and influenza viruses in patients ≥5 years (OR 2.8, 95% CI 1.5-5.4, p = 0.002). IPD treatment was documented in 702/708 cases; all but one patient received antimicrobials, most commonly a beta-lactam (amoxicillin/ampicillin +/−gentamicin in 664/701, 94.7%). CONCLUSIONS: Viral nucleic acid was identified in the nasopharynx in half the patients admitted with clinically diagnosed pneumonia. Development of immunisations targeting common respiratory viruses is likely to reduce the incidence of pneumonia in children living refugee camps and similar settings.",2013 Sep 16,"['Turner, Paul', 'Turner, Claudia', 'Watthanaworawit, Wanitda', 'Carrara, Verena', 'Cicelia, Naw', 'Deglise, Carole', 'Phares, Christina', 'Ortega, Luis', 'Nosten, Francois']",BMC Infect Dis,,,True
112c03868171e79e5f64b72e7c837fd4875d88f4,PMC,Comparison of viremia of type II porcine reproductive and respiratory syndrome virus in naturally infected pigs by zip nucleic acid probe-based real-time PCR,http://dx.doi.org/10.1186/1746-6148-9-181,PMC3847877,24028493,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a RNA virus with high genetic variation. This virus causes significant economic losses in most pig-producing countries. The clinical presentation of PRRSV ranges from asymptomatic to devastating. In this study, we developed a sensitive and specific zip nucleic acid probe-based real-time PCR assay to evaluate the viremia of natural PRRSV-infected pigs in Taiwan. Serum samples were collected from 577 pigs aged 5–12 weeks. These include 444 clinically healthy pigs and 133 symptomatic pigs were confirmed to have porcine respiratory disease complex (PRDC). RESULTS: Viremia was quantified in 79 of the 444 (17.8%) clinically healthy pigs and in 112 of the 133 (84.2%) PRDC cases. Viremias were significantly more common in pigs with PRDC compared with the clinically healthy pigs (P <0.0001). These results suggest that a high viral load is a major feature of PRRSV-affected pigs. CONCLUSIONS: ZNA probe-based real-time PCR can be a useful tool to diagnose symptomatic and asymptomatic PRRSV-infected pigs. The presence of this marker in a sample of animals with high PRRSV loads (>10(4.2) PRRSV genomes/μl of serum) seems to indicate that it correlates with the presence of PRDC in pigs.",2013 Sep 12,"['Lin, Chao-Nan', 'Lin, Wei-Hao', 'Hung, Li-Ning', 'Wang, Sheng-Yuan', 'Chiou, Ming-Tang']",BMC Vet Res,,,True
3d7aeae7fc9f39f80a461b590c16fd9ea37aa9d7,PMC,Differential cellular gene expression in duck trachea infected with a highly or low pathogenic H5N1 avian influenza virus,http://dx.doi.org/10.1186/1743-422X-10-279,PMC3848638,24015922,CC BY,"BACKGROUND: Avian influenza A (AI) viruses of subtypes H5 can cause serious disease outbreaks in poultry including panzootic due to H5N1 highly pathogenic (HP) viruses. These viruses are a threat not only for animal health but also public health due to their zoonotic potential. The domestic duck plays a major role in the epidemiological cycle of influenza virus subtypes H5 but little is known concerning host/pathogen interactions during influenza infection in duck species. In this study, a subtracted library from duck trachea (a primary site of influenza virus infection) was constructed to analyse and compare the host response after a highly or low pathogenic (LP) H5N1-infection. RESULTS: Here, we show that more than 200 different genes were differentially expressed in infected duck trachea to a significant degree. In addition, significant differentially expressed genes between LPAI- and HPAI-infected tracheas were observed. Gene ontology annotation was used and specific signalling pathways were identified. These pathways were different for LPAI and HPAI-infected tracheas, except for the CXCR4 signalling pathway which is implicated in immune response. A different modulation of genes in the CXCR4 signalling pathway and TRIM33 was induced in duck tracheas infected with a HPAI- or a LPAI-H5N1. CONCLUSION: First, this study indicates that Suppressive Subtractive Hybridization (SSH) is an alternative approach to gain insights into the pathogenesis of influenza infection in ducks. Secondly, the results indicate that cellular gene expression in the duck trachea was differently modulated after infection with a LPAI-H5N1 or after infection with a HPAI-H5N1 virus. Such difference found in infected trachea, a primary infection site, could precede continuation of infection and could explain appearance of respiratory symptoms or not.",2013 Sep 10,"['Massin, Pascale', 'Deleage, Claire', 'Oger, Aurélie', 'Briand, François-Xavier', 'Quenault, Hélène', 'Blanchard, Yannick']",Virol J,,,True
287efc07973e7b2d046c7664771dc2e2a00b501b,PMC,First infection by all four non-severe acute respiratory syndrome human coronaviruses takes place during childhood,http://dx.doi.org/10.1186/1471-2334-13-433,PMC3848659,24040960,CC BY,"BACKGROUND: Non-severe acute respiratory syndrome (non-SARS)-related human coronaviruses (HCoVs), including HCoV-229E, -HKU1, -NL63, and -OC43, have been detected in respiratory tract samples from children and adults. However, the natural prevalence of antibodies against these viruses in serum among population is unknown. METHODS: To measure antibodies to the spike (S) protein of the four common non-SARS HCoVs, recombinant S proteins of the four HCoVs were expressed and characterised in 293 T cell. An S-protein-based indirect immunofluorescence assay (IFA) was then developed to detect anti-S IgG and IgM for the four individual HCoVs and applied to serum samples from a general asymptomatic population (218 children and 576 adults) in Beijing. RESULTS: Of 794 blood samples tested, only 29 (3.65%) were negative for anti-S IgG. The seropositivity of the four anti-S IgG antibodies was >70% within the general population. The majority of seroconversions to four-HCoV positivity first occurred in children. Both S-IgG and S-IgM antibodies were detectable among children and increased with age, reaching a plateau at 6 years of age. However, no anti-S IgM was detected in healthy adults. CONCLUSION: Large proportions of children and adults in Beijing have evidence of anti-S IgG against four the HCoVs, and first infections by all four non-SARS HCoVs takes place during childhood.",2013 Sep 16,"['Zhou, Weimin', 'Wang, Wen', 'Wang, Huijuan', 'Lu, Roujian', 'Tan, Wenjie']",BMC Infect Dis,,,True
0480084eefee6333df832a821af8945ea7ab379a,PMC,A survey of visitors on Swedish livestock farms with reference to the spread of animal diseases,http://dx.doi.org/10.1186/1746-6148-9-184,PMC3848732,24040830,CC BY,"BACKGROUND: In addition to livestock movements, other between-farm contacts such as visitors may contribute to the spread of contagious animal diseases. Knowledge about such contacts is essential for contingency planning. Preventive measures, risk-based surveillance and contact tracing may be facilitated if the frequency and type of between-farm contacts can be assessed for different types of farms. The aim of this study was to investigate the frequency and types of visitors on farms with cloven-hoofed animals in Sweden and to analyse whether there were differences in the number of visitors attributable to region, season, and type of herd. Data were collected from Swedish farmers through contact-logs covering two-week periods during four different seasons. RESULTS: In total, 482 (32%) farmers filled in the contact log for at least one period and the data represent 18,416 days. The average number of professional and non-professional visitors per day was 0.3 and 0.8, respectively. Whereas the number of professional visitors seemed to increase with increasing herd size, this relation was not seen for non-professional visits. The mean numbers of visitors per day were highest in the summer and in the farm category ‘small mixed farm’. Reports of the visitors’ degree of contact with the animals showed that veterinarians, AI-technicians, animal transporters and neighbours were often in direct contact with the animals or entered the stables and 8.8% of the repairmen were also in direct contact with animals, which was unexpected. In a multivariable analysis, species, herd size and season were significantly associated with the number of professional visitors as well as the number of visitors in direct contact with the animals. CONCLUSION: In conclusion there was a large variation between farms in the number and type of contacts. The number of visitors that may be more likely to spread diseases between farms was associated with animal species and herd size.",2013 Sep 16,"['Nöremark, Maria', 'Frössling, Jenny', 'Lewerin, Susanna Sternberg']",BMC Vet Res,,,True
712dc64a26edbb44c0e9372a9443f7292a87bf80,PMC,A survey of visitors on Swedish livestock farms with reference to the spread of animal diseases,http://dx.doi.org/10.1186/1746-6148-9-184,PMC3848732,24040830,CC BY,"BACKGROUND: In addition to livestock movements, other between-farm contacts such as visitors may contribute to the spread of contagious animal diseases. Knowledge about such contacts is essential for contingency planning. Preventive measures, risk-based surveillance and contact tracing may be facilitated if the frequency and type of between-farm contacts can be assessed for different types of farms. The aim of this study was to investigate the frequency and types of visitors on farms with cloven-hoofed animals in Sweden and to analyse whether there were differences in the number of visitors attributable to region, season, and type of herd. Data were collected from Swedish farmers through contact-logs covering two-week periods during four different seasons. RESULTS: In total, 482 (32%) farmers filled in the contact log for at least one period and the data represent 18,416 days. The average number of professional and non-professional visitors per day was 0.3 and 0.8, respectively. Whereas the number of professional visitors seemed to increase with increasing herd size, this relation was not seen for non-professional visits. The mean numbers of visitors per day were highest in the summer and in the farm category ‘small mixed farm’. Reports of the visitors’ degree of contact with the animals showed that veterinarians, AI-technicians, animal transporters and neighbours were often in direct contact with the animals or entered the stables and 8.8% of the repairmen were also in direct contact with animals, which was unexpected. In a multivariable analysis, species, herd size and season were significantly associated with the number of professional visitors as well as the number of visitors in direct contact with the animals. CONCLUSION: In conclusion there was a large variation between farms in the number and type of contacts. The number of visitors that may be more likely to spread diseases between farms was associated with animal species and herd size.",2013 Sep 16,"['Nöremark, Maria', 'Frössling, Jenny', 'Lewerin, Susanna Sternberg']",BMC Vet Res,,,False
73761176155e77d6873806dd9579f59e5419111a,PMC,An easy operating pathogen microarray (EOPM) platform for rapid screening of vertebrate pathogens,http://dx.doi.org/10.1186/1471-2334-13-437,PMC3848773,24053492,CC BY,"BACKGROUND: Infectious diseases emerge frequently in China, partly because of its large and highly mobile population. Therefore, a rapid and cost-effective pathogen screening method with broad coverage is required for prevention and control of infectious diseases. The availability of a large number of microbial genome sequences generated by conventional Sanger sequencing and next generation sequencing has enabled the development of a high-throughput high-density microarray platform for rapid large-scale screening of vertebrate pathogens. METHODS: An easy operating pathogen microarray (EOPM) was designed to detect almost all known pathogens and related species based on their genomic sequences. For effective identification of pathogens from EOPM data, a statistical enrichment algorithm has been proposed, and further implemented in a user-friendly web-based interface. RESULTS: Using multiple probes designed to specifically detect a microbial genus or species, EOPM can correctly identify known pathogens at the species or genus level in blinded testing. Despite a lower sensitivity than PCR, EOPM is sufficiently sensitive to detect the predominant pathogens causing clinical symptoms. During application in two recent clinical infectious disease outbreaks in China, EOPM successfully identified the responsible pathogens. CONCLUSIONS: EOPM is an effective surveillance platform for infectious diseases, and can play an important role in infectious disease control.",2013 Sep 20,"['Huang, Weiwei', 'Yang, Yinhui', 'Zhang, Xinlei', 'Zhao, Changan', 'Yin, Aihua', 'Zhang, Xiaozhuang', 'He, Zhengxin', 'Jiang, Yongqiang', 'Zhang, Liang']",BMC Infect Dis,,,True
5b263e22abc98f73d06f4d7baa292027c941f3c6,PMC,Dengue virus infection induces autophagy: an in vivo study,http://dx.doi.org/10.1186/1423-0127-20-65,PMC3848819,24011333,CC BY,"BACKGROUND: We and others have reported that autophagy is induced by dengue viruses (DVs) in various cell lines, and that it plays a supportive role in DV replication. This study intended to clarify whether DV infection could induce autophagy in vivo. Furthermore, the effect of DV induced autophagy on viral replication and DV-related pathogenesis was investigated. RESULTS AND CONCLUSIONS: The physiopathological parameters were evaluated after DV2 was intracranially injected into 6-day-old ICR suckling mice. Autophagy-related markers were monitored by immunohistochemical/immunofluorescent staining and Western blotting. Double-membrane autophagic vesicles were investigated by transmission-electron-microscopy. DV non-structural-protein-1 (NS1) expression (indicating DV infection) was detected in the cerebrum, medulla and midbrain of the infected mice. In these infected tissues, increased LC3 puncta formation, LC3-II expression, double-membrane autophagosome-like vesicles (autophagosome), amphisome, and decreased p62 accumulation were observed, indicating that DV2 induces the autophagic progression in vivo. Amphisome formation was demonstrated by colocalization of DV2-NS1 protein or LC3 puncta and mannose-6-phosphate receptor (MPR, endosome marker) in DV2-infected brain tissues. We further manipulated DV-induced autophagy by the inducer rapamycin and the inhibitor 3-methyladenine (3MA), which accordingly promoted or suppressed the disease symptoms and virus load in the brain of the infected mice. We demonstrated that DV2 infection of the suckling mice induces autophagy, which plays a promoting role in DV replication and pathogenesis.",2013 Sep 8,"['Lee, Ying-Ray', 'Hu, Hsuan-Yun', 'Kuo, Szu-Han', 'Lei, Huan-Yao', 'Lin, Yee-Shin', 'Yeh, Trai-Ming', 'Liu, Ching-Chuan', 'Liu, Hsiao-Sheng']",J Biomed Sci,,,True
cd2c52484c1f755ce9d2c18174aae3ae879d221f,PMC,Dengue virus infection induces autophagy: an in vivo study,http://dx.doi.org/10.1186/1423-0127-20-65,PMC3848819,24011333,CC BY,"BACKGROUND: We and others have reported that autophagy is induced by dengue viruses (DVs) in various cell lines, and that it plays a supportive role in DV replication. This study intended to clarify whether DV infection could induce autophagy in vivo. Furthermore, the effect of DV induced autophagy on viral replication and DV-related pathogenesis was investigated. RESULTS AND CONCLUSIONS: The physiopathological parameters were evaluated after DV2 was intracranially injected into 6-day-old ICR suckling mice. Autophagy-related markers were monitored by immunohistochemical/immunofluorescent staining and Western blotting. Double-membrane autophagic vesicles were investigated by transmission-electron-microscopy. DV non-structural-protein-1 (NS1) expression (indicating DV infection) was detected in the cerebrum, medulla and midbrain of the infected mice. In these infected tissues, increased LC3 puncta formation, LC3-II expression, double-membrane autophagosome-like vesicles (autophagosome), amphisome, and decreased p62 accumulation were observed, indicating that DV2 induces the autophagic progression in vivo. Amphisome formation was demonstrated by colocalization of DV2-NS1 protein or LC3 puncta and mannose-6-phosphate receptor (MPR, endosome marker) in DV2-infected brain tissues. We further manipulated DV-induced autophagy by the inducer rapamycin and the inhibitor 3-methyladenine (3MA), which accordingly promoted or suppressed the disease symptoms and virus load in the brain of the infected mice. We demonstrated that DV2 infection of the suckling mice induces autophagy, which plays a promoting role in DV replication and pathogenesis.",2013 Sep 8,"['Lee, Ying-Ray', 'Hu, Hsuan-Yun', 'Kuo, Szu-Han', 'Lei, Huan-Yao', 'Lin, Yee-Shin', 'Yeh, Trai-Ming', 'Liu, Ching-Chuan', 'Liu, Hsiao-Sheng']",J Biomed Sci,,,False
820948b4ad6cf7e7272ef197612b1246e2117756,PMC,Dengue virus infection induces autophagy: an in vivo study,http://dx.doi.org/10.1186/1423-0127-20-65,PMC3848819,24011333,CC BY,"BACKGROUND: We and others have reported that autophagy is induced by dengue viruses (DVs) in various cell lines, and that it plays a supportive role in DV replication. This study intended to clarify whether DV infection could induce autophagy in vivo. Furthermore, the effect of DV induced autophagy on viral replication and DV-related pathogenesis was investigated. RESULTS AND CONCLUSIONS: The physiopathological parameters were evaluated after DV2 was intracranially injected into 6-day-old ICR suckling mice. Autophagy-related markers were monitored by immunohistochemical/immunofluorescent staining and Western blotting. Double-membrane autophagic vesicles were investigated by transmission-electron-microscopy. DV non-structural-protein-1 (NS1) expression (indicating DV infection) was detected in the cerebrum, medulla and midbrain of the infected mice. In these infected tissues, increased LC3 puncta formation, LC3-II expression, double-membrane autophagosome-like vesicles (autophagosome), amphisome, and decreased p62 accumulation were observed, indicating that DV2 induces the autophagic progression in vivo. Amphisome formation was demonstrated by colocalization of DV2-NS1 protein or LC3 puncta and mannose-6-phosphate receptor (MPR, endosome marker) in DV2-infected brain tissues. We further manipulated DV-induced autophagy by the inducer rapamycin and the inhibitor 3-methyladenine (3MA), which accordingly promoted or suppressed the disease symptoms and virus load in the brain of the infected mice. We demonstrated that DV2 infection of the suckling mice induces autophagy, which plays a promoting role in DV replication and pathogenesis.",2013 Sep 8,"['Lee, Ying-Ray', 'Hu, Hsuan-Yun', 'Kuo, Szu-Han', 'Lei, Huan-Yao', 'Lin, Yee-Shin', 'Yeh, Trai-Ming', 'Liu, Ching-Chuan', 'Liu, Hsiao-Sheng']",J Biomed Sci,,,False
3273d1af75cb33dbbec0d61dded9d576fe946030,PMC,Calculation of Evolutionary Correlation between Individual Genes and Full-Length Genome: A Method Useful for Choosing Phylogenetic Markers for Molecular Epidemiology,http://dx.doi.org/10.1371/journal.pone.0081106,PMC3849185,24312527,CC BY,"Individual genes or regions are still commonly used to estimate the phylogenetic relationships among viral isolates. The genomic regions that can faithfully provide assessments consistent with those predicted with full-length genome sequences would be preferable to serve as good candidates of the phylogenetic markers for molecular epidemiological studies of many viruses. Here we employed a statistical method to evaluate the evolutionary relationships between individual viral genes and full-length genomes without tree construction as a way to determine which gene can match the genome well in phylogenetic analyses. This method was performed by calculation of linear correlations between the genetic distance matrices of aligned individual gene sequences and aligned genome sequences. We applied this method to the phylogenetic analyses of porcine circovirus 2 (PCV2), measles virus (MV), hepatitis E virus (HEV) and Japanese encephalitis virus (JEV). Phylogenetic trees were constructed for comparisons and the possible factors affecting the method accuracy were also discussed in the calculations. The results revealed that this method could produce results consistent with those of previous studies about the proper consensus sequences that could be successfully used as phylogenetic markers. And our results also suggested that these evolutionary correlations could provide useful information for identifying genes that could be used effectively to infer the genetic relationships.",2013 Dec 3,"['Wang, Shuai', 'Luo, Xuenong', 'Wei, Wei', 'Zheng, Yadong', 'Dou, Yongxi', 'Cai, Xuepeng']",PLoS One,,,True
599f44a88bfd9fcd7cc5b03f3b0bf01c9b3c5ba8,PMC,Incubation periods of viral gastroenteritis: a systematic review,http://dx.doi.org/10.1186/1471-2334-13-446,PMC3849296,24066865,CC BY,"BACKGROUND: Accurate knowledge of incubation period is important to investigate and to control infectious diseases and their transmission, however statements of incubation period in the literature are often uncited, inconsistent, and/or not evidence based. METHODS: In a systematic review of the literature on five enteric viruses of public health importance, we found 256 articles with incubation period estimates, including 33 with data for pooled analysis. RESULTS: We fit a log-normal distribution to pooled data and found the median incubation period to be 4.5 days (95% CI 3.9-5.2 days) for astrovirus, 1.2 days (95% CI 1.1-1.2 days) for norovirus genogroups I and II, 1.7 days (95% CI 1.5-1.8 days) for sapovirus, and 2.0 days (95% CI 1.4-2.4 days) for rotavirus. CONCLUSIONS: Our estimates combine published data and provide sufficient quantitative detail to allow for these estimates to be used in a wide range of clinical and modeling applications. This can translate into improved prevention and control efforts in settings with transmission or the risk of transmission.",2013 Sep 25,"['Lee, Rachel M', 'Lessler, Justin', 'Lee, Rose A', 'Rudolph, Kara E', 'Reich, Nicholas G', 'Perl, Trish M', 'Cummings, Derek AT']",BMC Infect Dis,,,True
adbb0a486cf43c474df8b8b86fa6eacd422b171c,PMC,Evidence for the interaction of the human metapneumovirus G and F proteins during virus-like particle formation,http://dx.doi.org/10.1186/1743-422X-10-294,PMC3849350,24067107,CC BY,"BACKGROUND: Human metapneumovirus (HMPV) is now a major cause of lower respiratory infection in children. Although primary isolation of HMPV has been achieved in several different cell lines, the low level of virus replication and the subsequent recovery of low levels of infectious HMPV have hampered biochemical studies on the virus. These experimental methodologies usually require higher levels of biological material that can be achieved following HMPV infection. In this study we demonstrate that expression of the HMPV F, G and M proteins in mammalian cells leads to HMPV virus-like particles (VLP) formation. This experimental strategy will serve as a model system to allow the process of HMPV virus assembly to be examined. METHODS: The HMPV F, G and M proteins were expressed in mammalian cell lines. Protein cross-linking studies, sucrose gradient centrifugation and in situ imaging was used to examine interactions between the virus proteins. VLP formation was examined using sucrose density gradient centrifugation and electron microscopy analysis. RESULTS: Analysis of cells co-expressing the F, G and M proteins demonstrated that these proteins interacted. Furthermore, in cells co-expression the three HMPV proteins the formation VLPs was observed. Image analysis revealed the VLPs had a similar morphology to the filamentous virus morphology that we observed on HMPV-infected cells. The capacity of each protein to initiate VLP formation was examined using a VLP formation assay. Individual expression of each virus protein showed that the G protein was able to form VLPs in the absence of the other virus proteins. Furthermore, co-expression of the G protein with either the M or F proteins facilitated their incorporation into the VLP fraction. CONCLUSION: Co-expression of the F, G and M proteins leads to the formation of VLPs, and that incorporation of the F and M proteins into VLPs is facilitated by their interaction with the G protein. Our data suggests that the G protein plays a central role in VLP formation, and further suggests that the G protein may also play a role in the recruitment of the F and M proteins to sites of virus particle formation during HMPV infection.",2013 Sep 25,"['Loo, Liat Hui', 'Jumat, Muhammad Raihan', 'Fu, Yi', 'Ayi, Teck Choon', 'Wong, Pui San', 'Tee, Nancy WS', 'Tan, Boon Huan', 'Sugrue, Richard J']",Virol J,,,True
758c1e9d8c3cb652fe8ffc25e4b2b333cfb11ee1,PMC,Peptides Corresponding to the Predicted Heptad Repeat 2 Domain of the Feline Coronavirus Spike Protein Are Potent Inhibitors of Viral Infection,http://dx.doi.org/10.1371/journal.pone.0082081,PMC3849439,24312629,CC BY,"BACKGROUND: Feline infectious peritonitis (FIP) is a lethal immune-mediated disease caused by feline coronavirus (FCoV). Currently, no therapy with proven efficacy is available. In searching for agents that may prove clinically effective against FCoV infection, five analogous overlapping peptides were designed and synthesized based on the putative heptad repeat 2 (HR2) sequence of the spike protein of FCoV, and the antiviral efficacy was evaluated. METHODS: Plaque reduction assay and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxicity assay were performed in this study. Peptides were selected using a plaque reduction assay to inhibit Feline coronavirus infection. RESULTS: The results demonstrated that peptide (FP5) at concentrations below 20 μM inhibited viral replication by up to 97%. The peptide (FP5) exhibiting the most effective antiviral effect was further combined with a known anti-viral agent, human interferon-α (IFN-α), and a significant synergistic antiviral effect was observed. CONCLUSION: Our data suggest that the synthetic peptide FP5 could serve as a valuable addition to the current FIP prevention methods.",2013 Dec 3,"['Liu, I-Jung', 'Tsai, Wan-Ting', 'Hsieh, Li-En', 'Chueh, Ling-Ling']",PLoS One,,,True
a986a6d115df1e271c89a765800aa931ac3f6833,PMC,An evaluation of the global network of field epidemiology and laboratory training programmes: a resource for improving public health capacity and increasing the number of public health professionals worldwide,http://dx.doi.org/10.1186/1478-4491-11-45,PMC3849587,24053689,CC BY,"BACKGROUND: Given that many infectious diseases spread rapidly, across borders and species, there is a growing worldwide need to increase the number of public health professionals skilled in controlling infectious epidemics. Needed also are more public health professionals skilled in non-communicable disease surveillance and interventions. As a result, we surveyed all 57 field epidemiology training programmes (FETPs) that are members of the Training Program in Epidemiology and Public Health Interventions Network (TEPHINET), to evaluate the progress of the FETPs, the only global applied epidemiology network, toward increasing public health capacity globally. METHODS: Data on the FETP programmes and the training they provide were abstracted from TEPHINET membership surveys and verified with FETP directors for all FETPs that were members of TEPHINET in 2012. Data on abstracts submitted to the recent TEPHINET Global Scientific Conference, on recent accomplishments by each FETP, and on quality improvement were also compiled to provide a worldwide view of the public health human resource capacity produced by these programmes. RESULTS: A total of 6980 public health professionals worldwide have graduated from an FETP or from the Center for Disease Control and Prevention’s Epidemiology Intelligence Service (EIS). FETP residents and graduates participate in key public health prevention, control, and response activities. Each FETP has adapted its curriculum and objectives over time to align with its country’s public health priorities. FETPs are well integrated into their national public health infrastructures, and they have many partners at the national, regional and global levels. CONCLUSION: FETPs are a competent and diverse source of highly skilled public health professionals who contribute significantly to public health’s global human resource needs. This finding is evidenced by 1) the training curricula that were adapted over time to meet public health’s human resource needs, 2) the FETPs’ continued support from internal and external partners, 3) the increasing number of FETP residents and graduates and their increasing contribution to effective public health work, and 4) the increased quality improvement initiatives facilitated through the FETPs membership in one global network, TEPHINET.",2013 Sep 21,"['Subramanian, Renee E', 'Herrera, Dionisio G', 'Kelly, Paul M']",Hum Resour Health,,,True
2558f92b15a62a49fdd0e7621ba97f1a4aa0080d,PMC,The first detection of influenza in the Finnish pig population: a retrospective study,http://dx.doi.org/10.1186/1751-0147-55-69,PMC3850993,24047612,CC BY,"BACKGROUND: Swine influenza is an infectious acute respiratory disease of pigs caused by influenza A virus. We investigated the time of entry of swine influenza into the Finnish pig population. We also describe the molecular detection of two types of influenza A (H1N1) viruses in porcine samples submitted in 2009 and 2010. This retrospective study was based on three categories of samples: blood samples collected for disease monitoring from pigs at major slaughterhouses from 2007 to 2009; blood samples from pigs in farms with a special health status taken in 2008 and 2009; and diagnostic blood samples from pigs in farms with clinical signs of respiratory disease in 2008 and 2009. The blood samples were tested for influenza A antibodies with an antibody ELISA. Positive samples were further analyzed for H1N1, H3N2, and H1N2 antibodies with a hemagglutination inhibition test. Diagnostic samples for virus detection were subjected to influenza A M-gene-specific real-time RT-PCR and to pandemic influenza A H1N1-specific real-time RT-PCR. Positive samples were further analyzed with RT-PCRs designed for this purpose, and the PCR products were sequenced and sequences analyzed phylogenetically. RESULTS: In the blood samples from pigs in special health class farms producing replacement animals and in diagnostic blood samples, the first serologically positive samples originated from the period July–August 2008. In samples collected for disease monitoring, < 0.1%, 0% and 16% were positive for antibodies against influenza A H1N1 in the HI test in 2007, 2008, and 2009, respectively. Swine influenza A virus of avian-like H1N1 was first detected in diagnostic samples in February 2009. In 2009 and 2010, the avian-like H1N1 virus was detected on 12 and two farms, respectively. The pandemic H1N1 virus (A(H1N1)pdm09) was detected on one pig farm in 2009 and on two farms in 2010. CONCLUSIONS: Based on our study, swine influenza of avian-like H1N1 virus was introduced into the Finnish pig population in 2008 and A(H1N1)pdm09 virus in 2009. The source of avian-like H1N1 infection could not be determined. Cases of pandemic H1N1 in pigs coincided with the period when the A(H1N1)pdm09 virus was spread in humans in Finland.",2013 Sep 18,"['Nokireki, Tiina', 'Laine, Taina', 'London, Laura', 'Ikonen, Niina', 'Huovilainen, Anita']",Acta Vet Scand,,,True
55844fc8a5cb75ffa1a249436ad30d6d93792df5,PMC,"Transmission potential of influenza A/H7N9, February to May 2013, China",http://dx.doi.org/10.1186/1741-7015-11-214,PMC3851127,24083506,CC BY,"BACKGROUND: On 31 March 2013, the first human infections with the novel influenza A/H7N9 virus were reported in Eastern China. The outbreak expanded rapidly in geographic scope and size, with a total of 132 laboratory-confirmed cases reported by 3 June 2013, in 10 Chinese provinces and Taiwan. The incidence of A/H7N9 cases has stalled in recent weeks, presumably as a consequence of live bird market closures in the most heavily affected areas. Here we compare the transmission potential of influenza A/H7N9 with that of other emerging pathogens and evaluate the impact of intervention measures in an effort to guide pandemic preparedness. METHODS: We used a Bayesian approach combined with a SEIR (Susceptible-Exposed-Infectious-Removed) transmission model fitted to daily case data to assess the reproduction number (R) of A/H7N9 by province and to evaluate the impact of live bird market closures in April and May 2013. Simulation studies helped quantify the performance of our approach in the context of an emerging pathogen, where human-to-human transmission is limited and most cases arise from spillover events. We also used alternative approaches to estimate R based on individual-level information on prior exposure and compared the transmission potential of influenza A/H7N9 with that of other recent zoonoses. RESULTS: Estimates of R for the A/H7N9 outbreak were below the epidemic threshold required for sustained human-to-human transmission and remained near 0.1 throughout the study period, with broad 95% credible intervals by the Bayesian method (0.01 to 0.49). The Bayesian estimation approach was dominated by the prior distribution, however, due to relatively little information contained in the case data. We observe a statistically significant deceleration in growth rate after 6 April 2013, which is consistent with a reduction in A/H7N9 transmission associated with the preemptive closure of live bird markets. Although confidence intervals are broad, the estimated transmission potential of A/H7N9 appears lower than that of recent zoonotic threats, including avian influenza A/H5N1, swine influenza H3N2sw and Nipah virus. CONCLUSION: Although uncertainty remains high in R estimates for H7N9 due to limited epidemiological information, all available evidence points to a low transmission potential. Continued monitoring of the transmission potential of A/H7N9 is critical in the coming months as intervention measures may be relaxed and seasonal factors could promote disease transmission in colder months.",2013 Oct 2,"['Chowell, Gerardo', 'Simonsen, Lone', 'Towers, Sherry', 'Miller, Mark A', 'Viboud, Cécile']",BMC Med,,,True
257d3ac44f72e298b1b0c5f46561948b973ac3d5,PMC,Different virulence of porcine and porcine-like bovine rotavirus strains with genetically nearly identical genomes in piglets and calves,http://dx.doi.org/10.1186/1297-9716-44-88,PMC3851489,24083947,CC BY,"Direct interspecies transmissions of group A rotaviruses (RVA) have been reported under natural conditions. However, the pathogenicity of RVA has never been directly compared in homologous and heterologous hosts. The bovine RVA/Cow-tc/KOR/K5/2004/G5P[7] strain, which was shown to possess a typical porcine-like genotype constellation similar to that of the G5P[7] prototype RVA/Pig-tc/USA/OSU/1977/G5P9[7] strain, was examined for its pathogenicity and compared with the porcine G5P[7] RVA/Pig-tc/KOR/K71/2006/G5P[7] strain possessing the same genotype constellation. The bovine K5 strain induced diarrhea and histopathological changes in the small intestine of piglets and calves, whereas the porcine K71 strain caused diarrhea and histopathological changes in the small intestine of piglets, but not in calves. Furthermore, the bovine K5 strain showed extra-intestinal tropisms in both piglets and calves, whereas the porcine K71 strain had extra-intestinal tropisms in piglets, but not in calves. Therefore, we performed comparative genomic analysis of the K71 and K5 RVA strains to determine whether specific mutations could be associated with these distinct clinical and pathological phenotypes. Full-length sequencing analyses for the 11 genomic segments for K71 and K5 revealed that these strains were genetically nearly identical to each other. Two nucleotide mutations were found in the 5′ untranslated region (UTR) of NSP5 and the 3′ UTR of NSP3, and eight amino acid mutations in VP1-VP4 and NSP2. Some of these mutations may be critical molecular determinants for RVA virulence and/or pathogenicity.",2013 Oct 1,"['Park, Jun-Gyu', 'Kim, Hyun-Jeong', 'Matthijnssens, Jelle', 'Alfajaro, Mia Madel', 'Kim, Deok-Song', 'Son, Kyu-Yeol', 'Kwon, Hyoung-Jun', 'Hosmillo, Myra', 'Ryu, Eun-Hye', 'Kim, Ji-Yun', 'Cena, Rohani B', 'Lee, Ju-Hwan', 'Kang, Mun-Il', 'Park, Sang-Ik', 'Cho, Kyoung-Oh']",Vet Res,,,True
fda3a715b0db3802a398fdadcf819448672b339a,PMC,Different virulence of porcine and porcine-like bovine rotavirus strains with genetically nearly identical genomes in piglets and calves,http://dx.doi.org/10.1186/1297-9716-44-88,PMC3851489,24083947,CC BY,"Direct interspecies transmissions of group A rotaviruses (RVA) have been reported under natural conditions. However, the pathogenicity of RVA has never been directly compared in homologous and heterologous hosts. The bovine RVA/Cow-tc/KOR/K5/2004/G5P[7] strain, which was shown to possess a typical porcine-like genotype constellation similar to that of the G5P[7] prototype RVA/Pig-tc/USA/OSU/1977/G5P9[7] strain, was examined for its pathogenicity and compared with the porcine G5P[7] RVA/Pig-tc/KOR/K71/2006/G5P[7] strain possessing the same genotype constellation. The bovine K5 strain induced diarrhea and histopathological changes in the small intestine of piglets and calves, whereas the porcine K71 strain caused diarrhea and histopathological changes in the small intestine of piglets, but not in calves. Furthermore, the bovine K5 strain showed extra-intestinal tropisms in both piglets and calves, whereas the porcine K71 strain had extra-intestinal tropisms in piglets, but not in calves. Therefore, we performed comparative genomic analysis of the K71 and K5 RVA strains to determine whether specific mutations could be associated with these distinct clinical and pathological phenotypes. Full-length sequencing analyses for the 11 genomic segments for K71 and K5 revealed that these strains were genetically nearly identical to each other. Two nucleotide mutations were found in the 5′ untranslated region (UTR) of NSP5 and the 3′ UTR of NSP3, and eight amino acid mutations in VP1-VP4 and NSP2. Some of these mutations may be critical molecular determinants for RVA virulence and/or pathogenicity.",2013 Oct 1,"['Park, Jun-Gyu', 'Kim, Hyun-Jeong', 'Matthijnssens, Jelle', 'Alfajaro, Mia Madel', 'Kim, Deok-Song', 'Son, Kyu-Yeol', 'Kwon, Hyoung-Jun', 'Hosmillo, Myra', 'Ryu, Eun-Hye', 'Kim, Ji-Yun', 'Cena, Rohani B', 'Lee, Ju-Hwan', 'Kang, Mun-Il', 'Park, Sang-Ik', 'Cho, Kyoung-Oh']",Vet Res,,,False
e1400d2059ba0e337608df70a17351ee9c3caa17,PMC,Genetic and biological characterisation of an avian-like H1N2 swine influenza virus generated by reassortment of circulating avian-like H1N1 and H3N2 subtypes in Denmark,http://dx.doi.org/10.1186/1743-422X-10-290,PMC3851529,24047399,CC BY,"BACKGROUND: The influenza A virus subtypes H1N1, H1N2 and H3N2 are the most prevalent subtypes in swine. In 2003, a reassorted H1N2 swine influenza virus (SIV) subtype appeared and became prevalent in Denmark. In the present study, the reassortant H1N2 subtype was characterised genetically and the infection dynamics compared to an “avian-like” H1N1 virus by an experimental infection study. METHODS: Sequence analyses were performed of the H1N2 virus. Two groups of pigs were inoculated with the reassortant H1N2 virus and an “avian-like” H1N1 virus, respectively, followed by inoculation with the opposite subtype four weeks later. Measurements of HI antibodies and acute phase proteins were performed. Nasal virus excretion and virus load in lungs were determined by real-time RT-PCR. RESULTS: The phylogenetic analysis revealed that the reassorted H1N2 virus contained a European “avian-like” H1-gene and a European “swine-like” N2-gene, thus being genetically distinct from most H1N2 viruses circulating in Europe, but similar to viruses reported in 2009/2010 in Sweden and Italy. Sequence analyses of the internal genes revealed that the reassortment probably arose between circulating Danish “avian-like” H1N1 and H3N2 SIVs. Infected pigs developed cross-reactive antibodies, and increased levels of acute phase proteins after inoculations. Pigs inoculated with H1N2 exhibited nasal virus excretion for seven days, peaking day 1 after inoculation two days earlier than H1N1 infected pigs and at a six times higher level. The difference, however, was not statistically significant. Pigs euthanized on day 4 after inoculation, had a high virus load in all lung lobes. After the second inoculation, the nasal virus excretion was minimal. There were no clinical sign except elevated body temperature under the experimental conditions. CONCLUSIONS: The “avian-like” H1N2 subtype, which has been established in the Danish pig population at least since 2003, is a reassortant between circulating swine “avian-like” H1N1 and H3N2. The Danish H1N2 has an “avian-like” H1 and differs from most other reported H1N2 viruses in Europe and North America/Asia, which have H1-genes of human or “classical-swine” origin, respectively. The variant seems, however, also to be circulating in countries like Sweden and Italy. The infection dynamics of the reassorted “avian-like” H1N2 is similar to the older “avian-like” H1N1 subtype.",2013 Sep 18,"['Trebbien, Ramona', 'Bragstad, Karoline', 'Larsen, Lars Erik', 'Nielsen, Jens', 'Bøtner, Anette', 'Heegaard, Peter MH', 'Fomsgaard, Anders', 'Viuff, Birgitte', 'Hjulsager, Charlotte Kristiane']",Virol J,,,True
6360e58e9bb14d3e03b5c78025509ea6f9482bec,PMC,Selection of reference genes for quantitative real-time PCR analysis in chicken embryo fibroblasts infected with avian leukosis virus subgroup J,http://dx.doi.org/10.1186/1756-0500-6-402,PMC3851545,24099561,CC BY,"BACKGROUND: The selection of stably expressed reference genes is a prerequisite when evaluating gene expression, via real-time PCR, in cells in response to viral infections. The objective of our study was to identify suitable reference genes for mRNA expression analysis in chicken embryonic fibroblasts (CEF) after infection with avian leukosis virus subgroup J (ALV-J). FINDINGS: The expression levels of 11 potential reference genes in CEF infected with ALV-J were determined by real-time PCR. The expression stability of these genes were analyzed and ranked using the geNorm tool. Analysis indicated that the genes RPL30 (ribosomal protein L30) and SDHA (succinate dehydrogenase complex, subunit A) were the most stably expressed genes in the ALV-J infected CEF. CONCLUSIONS: The RPL30 and SDHA were deemed suitable for use as reference genes for real-time PCR analysis of mRNA gene expression during ALV-J infection, whereas commonly used ACTB and GAPDH are unsuitable to be reference genes.",2013 Oct 7,"['Yang, Falong', 'Lei, Xiaowen', 'Rodriguez-Palacios, Alexander', 'Tang, Cheng', 'Yue, Hua']",BMC Res Notes,,,True
d4c35983add63a4f8eee72b1d8fa864de4147ead,PMC,A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines,http://dx.doi.org/10.1371/journal.pone.0081587,PMC3852489,24324708,CC BY,"An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367–606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients’ lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection.",2013 Dec 4,"['Du, Lanying', 'Kou, Zhihua', 'Ma, Cuiqing', 'Tao, Xinrong', 'Wang, Lili', 'Zhao, Guangyu', 'Chen, Yaoqing', 'Yu, Fei', 'Tseng, Chien-Te K.', 'Zhou, Yusen', 'Jiang, Shibo']",PLoS One,,,True
aa1eaad52d7a7827850cecf3d6b582e728e7e543,PMC,Haemorrhagic pneumonia in sled dogs caused by Streptococcus equi subsp. zooepidemicus - one fatality and two full recoveries: a case report,http://dx.doi.org/10.1186/1751-0147-55-67,PMC3852515,24020788,CC BY,"In spite of yearly vaccination, outbreaks of canine infectious respiratory disease are periodically seen amongst domestic dogs. These infections compromise host defense mechanisms, and, when combined with other stressful events, allow opportunistic pathogens like Streptococcus equi subsp. zooepidemicus to create serious disease. Early recognition and treatment are tremendously important for a successful outcome in these cases. A polyvalent vaccine was given to 22 racing dogs three days after a competition, followed by two days of rest, and then the dogs were returned to regular training. Coughing was noticed among the dogs four days after immunisation. Three days after this outbreak one of the dogs was unusually silent and was found dead the next morning. Simultaneously two other dogs developed haemorrhagic expectorate, depression and dyspnea and were brought in to the veterinary hospital. Streptococcus equi subsp. zooepidemicus was isolated in pure culture from all three cases. They were treated and rehabilitated successfully, and won a sledge race three months later. This paper discusses the necropsy results, treatment regime, rehabilitation and the chronology of vaccination, stressful events and disease.",2013 Sep 11,"['Jaeger, Gry', 'Skogmo, Hege Kippenes', 'Kolbjørnsen, Øyvor', 'Larsen, Hans Jørgen Søiland', 'Bergsjø, Bjarne', 'Sørum, Henning']",Acta Vet Scand,,,True
096d707e74acc27426416dacf89d5d134a0b9866,PMC,Immunosuppression of the Trimellitic Anhydride-Induced Th2 Response by Novel Nonanatural Products Mixture in Mice,http://dx.doi.org/10.1155/2013/748123,PMC3852580,24348718,CC BY,"Many natural dietary products prevent or cure allergic inflammation; however, the ability of mixtures of these natural medicinals to suppress allergic skin inflammation is unknown. We examined the inhibitory effects of nonanatural products mixture (NPM-9), which provides immunoregulatory activation, on Th2-mediated skin allergic inflammation. Oral administration of NPM-9 in mice reduced ear thickness and specific IgE production in trimellitic anhydride- (TMA-)induced contact hypersensitivity (CHS). NPM-9 also suppressed IL-4 and IL-1β production in splenocytes but prevented only TMA-induced IL-1β production in inflamed ears. To characterize the mechanism of this effect, we examined NPM-9 immunosuppression on an OVA-induced Th2 allergic state. Oral administration of NPM-9 inhibited Th2-mediated serum IgE overproduction. NPM-9 also downregulated the polarized Th2 response, whereas it upregulated Th1 response in splenocytes. These data suggest that NPM-9 may be a useful therapeutic agent for allergic inflammatory diseases through its suppression of the Th2-mediated allergic response.",2013 Nov 19,"['Bae, Min-Jung', 'Shin, Hee Soon', 'Shon, Dong-Hwa']",Evid Based Complement Alternat Med,,,True
2a46fb28bde7f183808bb47ec90ffd8d97511a73,PMC,"Microbiological, pathological and histological findings in four Danish pig herds affected by a new neonatal diarrhoea syndrome",http://dx.doi.org/10.1186/1746-6148-9-206,PMC3852778,24119974,CC BY,"BACKGROUND: Neonatal diarrhoea is a frequent clinical condition in commercial swine herds, previously regarded to be uncomplicated to treat. However, since 2008 it seems that a new neonatal diarrhoeic syndrome unresponsive to antibiotics and common management practices has emerged. Routine laboratory examinations have not detected any pathogen related to this syndrome. The primary purpose of this study was to evaluate if well-known enteric pathogens could be associated with outbreaks of neonatal diarrhoea, thus question the hypotheses of a new syndrome. Furthermore, we wanted to evaluate macroscopic and microscopic findings associated with these outbreaks and if possible propose a preliminary piglet-level case-definition on syndrome New Neonatal Porcine Diarrhoea syndrome (NNPDS). RESULTS: Four well-managed herds experiencing neonatal diarrhoea with no previously established laboratory conclusion and suspected to suffer from New Neonatal Porcine Diarrhoea Syndrome, were selected. Within these herds, 51 diarrhoeic and 50 non-diarrhoeic piglets at the age of three to seven days were necropsied and subjected to histological and microbiological examination. Faeces were non-haemorrhagic. Neither enterotoxigenic E. coli, Clostridium perfringens type A or C, Clostridium difficile, rotavirus, coronavirus, Cryptosporidium spp, Giardia spp, Cystoisospora suis nor Strongyloides ransomi were associated with diarrhoea in the investigated outbreaks. Macroscopically, the diarrhoeic piglets were characterized by filled stomachs and flaccid intestines without mucosal changes. The predominant histological lesions were villous atrophy in jejunum and ileum. Epithelial lesions in colon were seen in one third of the case piglets. CONCLUSIONS: The results of the study supported the hypothesis that a new neonatal porcine diarrhoea was present in the investigated herds, since no known pathogen(s) or management factors could explain the diarrhoeal outbreaks. Based on the findings in the four herds the following case-definition of NNPDS was suggested: Non-haemorrhagic diarrhoea during the first week of life, without detection of known infectious pathogens, characterized by milk-filled stomachs and flaccid intestines at necropsy.",2013 Oct 12,"['Kongsted, Hanne', 'Jonach, Beata', 'Haugegaard, Svend', 'Angen, Øystein', 'Jorsal, Sven E', 'Kokotovic, Branko', 'Larsen, Lars E', 'Jensen, Tim K', 'Nielsen, Jens P']",BMC Vet Res,,,True
5a2360e93ec038502133c97cf78a114c012e5df4,PMC,Whole genome methylation array analysis reveals new aspects in Balkan endemic nephropathy etiology,http://dx.doi.org/10.1186/1471-2369-14-225,PMC3852817,24131581,CC BY,"BACKGROUND: Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephritis in striking correlation with uroepithelial tumours of the upper urinary tract. The disease has endemic distribution in the Danube river regions in several Balkan countries. DNA methylation is a primary epigenetic modification that is involved in major processes such as cancer, genomic imprinting, gene silencing, etc. The significance of CpG island methylation status in normal development, cell differentiation and gene expression is widely recognized, although still stays poorly understood. METHODS: We performed whole genome DNA methylation array analysis on DNA pool samples from peripheral blood from 159 affected individuals and 170 healthy individuals. This technique allowed us to determine the methylation status of 27 627 CpG islands throughout the whole genome in healthy controls and BEN patients. Thus we obtained the methylation profile of BEN patients from Bulgarian and Serbian endemic regions. RESULTS: Using specifically developed software we compared the methylation profiles of BEN patients and corresponding controls and revealed the differently methylated regions. We then compared the DMRs between all patient-control pairs to determine common changes in the epigenetic profiles. SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs. The CpG islands of all 3 genes were hypomethylated compared to controls. This suggests that dysregulation of these genes involved in immunological response could be a common mechanism in BEN pathogenesis in both endemic regions and in both genders. CONCLUSION: Our data propose a new hypothesis that immunologic dysregulation has a place in BEN etiopathogenesis.",2013 Oct 16,"['Staneva, Rada', 'Rukova, Blaga', 'Hadjidekova, Savina', 'Nesheva, Desislava', 'Antonova, Olga', 'Dimitrov, Plamen', 'Simeonov, Valeri', 'Stamenov, Georgi', 'Cukuranovic, Rade', 'Cukuranovic, Jovana', 'Stefanovic, Vladislav', 'Polenakovic, Momir', 'Dimova, Ivanka', 'Hlushchuk, Ruslan', 'Djonov, Valentin', 'Galabov, Angel', 'Toncheva, Draga']",BMC Nephrol,,,True
588ad9cd788e0631c93e4164f98489d9b3f30811,PMC,Adaptive evolution of bat dipeptidyl peptidase 4 (dpp4): implications for the origin and emergence of Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1186/1743-422X-10-304,PMC3852826,24107353,CC BY,"BACKGROUND: The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) that first appeared in Saudi Arabia during the summer of 2012 has to date (20th September 2013) caused 58 human deaths. MERS-CoV utilizes the dipeptidyl peptidase 4 (DPP4) host cell receptor, and analysis of the long-term interaction between virus and receptor provides key information on the evolutionary events that lead to the viral emergence. FINDINGS: We show that bat DPP4 genes have been subject to significant adaptive evolution, suggestive of a long-term arms-race between bats and MERS related CoVs. In particular, we identify three positively selected residues in DPP4 that directly interact with the viral surface glycoprotein. CONCLUSIONS: Our study suggests that the evolutionary lineage leading to MERS-CoV may have circulated in bats for a substantial time period.",2013 Oct 10,"['Cui, Jie', 'Eden, John-Sebastian', 'Holmes, Edward C', 'Wang, Lin-Fa']",Virol J,,,True
fb0191a305e3289b1be275259659e20b096247b5,PMC,SSW Library: An SIMD Smith-Waterman C/C++ Library for Use in Genomic Applications,http://dx.doi.org/10.1371/journal.pone.0082138,PMC3852983,24324759,CC BY,"BACKGROUND: The Smith-Waterman algorithm, which produces the optimal pairwise alignment between two sequences, is frequently used as a key component of fast heuristic read mapping and variation detection tools for next-generation sequencing data. Though various fast Smith-Waterman implementations are developed, they are either designed as monolithic protein database searching tools, which do not return detailed alignment, or are embedded into other tools. These issues make reusing these efficient Smith-Waterman implementations impractical. RESULTS: To facilitate easy integration of the fast Single-Instruction-Multiple-Data Smith-Waterman algorithm into third-party software, we wrote a C/C++ library, which extends Farrar’s Striped Smith-Waterman (SSW) to return alignment information in addition to the optimal Smith-Waterman score. In this library we developed a new method to generate the full optimal alignment results and a suboptimal score in linear space at little cost of efficiency. This improvement makes the fast Single-Instruction-Multiple-Data Smith-Waterman become really useful in genomic applications. SSW is available both as a C/C++ software library, as well as a stand-alone alignment tool at: https://github.com/mengyao/Complete-Striped-Smith-Waterman-Library. CONCLUSIONS: The SSW library has been used in the primary read mapping tool MOSAIK, the split-read mapping program SCISSORS, the MEI detector TANGRAM, and the read-overlap graph generation program RZMBLR. The speeds of the mentioned software are improved significantly by replacing their ordinary Smith-Waterman or banded Smith-Waterman module with the SSW Library.",2013 Dec 4,"['Zhao, Mengyao', 'Lee, Wan-Ping', 'Garrison, Erik P.', 'Marth, Gabor T.']",PLoS One,,,True
864336d3d1a34686efdd078534a092fc888c2c3f,PMC,Agent based modeling of Treg-Teff cross regulation in relapsing-remitting multiple sclerosis,http://dx.doi.org/10.1186/1471-2105-14-S16-S9,PMC3853330,24564794,CC BY,BACKGROUND: Multiple sclerosis (MS) is a disease of central nervous system that causes the removal of fatty myelin sheath from axons of the brain and spinal cord. Autoimmunity plays an important role in this pathology outcome and body's own immune system attacks on the myelin sheath causing the damage. The etiology of the disease is partially understood and the response to treatment cannot easily be predicted. RESULTS: We presented the results obtained using 8 genetically predisposed randomly chosen individuals reproducing both the absence and presence of malfunctions of the Teff-Treg cross-balancing mechanisms at a local level. For simulating the absence of a local malfunction we supposed that both Teff and Treg populations had similar maximum duplication rates. Results presented here suggest that presence of a genetic predisposition is not always a sufficient condition for developing the disease. Other conditions such as a breakdown of the mechanisms that regulate and allow peripheral tolerance should be involved. CONCLUSIONS: The presented model allows to capture the essential dynamics of relapsing-remitting MS despite its simplicity. It gave useful insights that support the hypothesis of a breakdown of Teff-Treg cross balancing mechanisms.,2013 Oct 22,"['Pennisi, Marzio', 'Rajput, Abdul-Mateen', 'Toldo, Luca', 'Pappalardo, Francesco']",BMC Bioinformatics,,,True
2f4331d2427906e96afeb82ef5c4a90dda236470,PMC,Anti HSV-1 Activity of Halistanol Sulfate and Halistanol Sulfate C Isolated from Brazilian Marine Sponge Petromica citrina (Demospongiae),http://dx.doi.org/10.3390/md11114176,PMC3853722,24172213,CC BY,"The n-butanol fraction (BF) obtained from the crude extract of the marine sponge Petromica citrina, the halistanol-enriched fraction (TSH fraction), and the isolated compounds halistanol sulfate (1) and halistanol sulfate C (2), were evaluated for their inhibitory effects on the replication of the Herpes Simplex Virus type 1 (HSV-1, KOS strain) by the viral plaque number reduction assay. The TSH fraction was the most effective against HSV-1 replication (SI = 15.33), whereas compounds 1 (SI = 2.46) and 2 (SI = 1.95) were less active. The most active fraction and these compounds were also assayed to determine the viral multiplication step(s) upon which they act as well as their potential synergistic effects. The anti-HSV-1 activity detected was mediated by the inhibition of virus attachment and by the penetration into Vero cells, the virucidal effect on virus particles, and by the impairment in levels of ICP27 and gD proteins of HSV-1. In summary, these results suggest that the anti-HSV-1 activity of TSH fraction detected is possibly related to the synergic effects of compounds 1 and 2.",2013 Oct 29,"['da Rosa Guimarães, Tatiana', 'Quiroz, Carlos Guillermo', 'Rigotto, Caroline', 'de Oliveira, Simone Quintana', 'Rojo de Almeida, Maria Tereza', 'Bianco, Éverson Miguel', 'Moritz, Maria Izabel Goulart', 'Carraro, João Luís', 'Palermo, Jorge Alejandro', 'Cabrera, Gabriela', 'Schenkel, Eloir Paulo', 'Reginatto, Flávio Henrique', 'Oliveira Simões, Cláudia Maria']",Mar Drugs,,,True
f53604d28e212733384d7ec28e84d4a62e506254,PMC,Serological Evidence for Multiple Strains of Canine Norovirus in the UK Dog Population,http://dx.doi.org/10.1371/journal.pone.0081596,PMC3855277,24339947,CC BY,"Noroviruses are associated with intestinal disease in humans, cows, pigs, mice, and, more recently, dogs. In 2007, the first canine norovirus (CNV) was identified and characterized in Italy. Subsequent studies have identified CNV in stools of dogs from Portugal, Greece, and the United States. To investigate the prevalence of CNV in the UK dog population, 228 canine stool samples were screened for CNV by qPCR, and 396 serum samples were screened for anti-CNV antibodies. qPCR of RNA extracted from canine stool samples did not reveal any CNV-positive samples, based on samples collected from diarrhoeic and control dogs in 2012–2013. CNV virus-like particles to three different CNV strains were produced using recombinant baculoviruses and a seroprevalence screen undertaken. Anti-CNV antibodies were identified at significant levels in canine serum; 38.1% of samples collected between 1999–2001 and 60.1% of samples collected in 2012–2013 were seropositive. The increase in seroprevalence over time (p<0.001) suggests that the CNV strains screened for are becoming more widespread. Variation in seroprevalence to different CNV strains was also identified. Two-thirds of the dogs were seropositive to a single strain, whereas the remaining third were seropositive to two or three of the strains analysed. This study has provided the first evidence that CNV is present in the UK, with seroprevalence identified to multiple circulating strains. This warrants further study and increased awareness of this recently discovered canine virus.",2013 Dec 5,"['Caddy, Sarah', 'Emmott, Edward', 'El-Attar, Laila', 'Mitchell, Judy', 'de Rougemont, Alexis', 'Brownlie, Joe', 'Goodfellow, Ian']",PLoS One,,,True
6e1a04ccbbb614c9a28dd37899d7537f907028a8,PMC,Cytoplasmic Viruses: Rage against the (Cellular RNA Decay) Machine,http://dx.doi.org/10.1371/journal.ppat.1003762,PMC3855480,24339774,CC BY,,2013 Dec 5,"['Moon, Stephanie L.', 'Wilusz, Jeffrey']",PLoS Pathog,,,True
394b9e259a4a871f49e3ab9209a05059fb6347ed,PMC,A Multigene Approach for Comparing Genealogy of Betacoronavirus from Cattle and Horses,http://dx.doi.org/10.1155/2013/349702,PMC3855977,24348152,CC BY,"Gastroenteritis is one of the leading causes of morbidity and mortality among young and newborn animals and is often caused by multiple intestinal infections, with rotavirus and bovine coronavirus (BCoV) being the main viral causes in cattle. Given that BCoV is better studied than equine coronaviruses and given the possibility of interspecies transmission of these viruses, this research was designed to compare the partial sequences of the spike glycoprotein (S), hemagglutinin-esterase protein (HE), and nucleoprotein (N) genes from coronaviruses from adult cattle with winter dysentery, calves with neonatal diarrhea, and horses. To achieve this, eleven fecal samples from dairy cows with winter dysentery, three from calves, and two from horses, all from Brazil, were analysed. It could be concluded that the enteric BCoV genealogy from newborn and adult cattle is directly associated with geographic distribution patterns, when S and HE genes are taken into account. A less-resolved genealogy exists for the HE and N genes in cattle, with a trend for an age-related segregation pattern. The coronavirus strains from horses revealed Betacoronavirus sequences indistinguishable from those found in cattle, a fact previously unknown.",2013 Nov 17,"['Barros, Iracema N.', 'Silva, Sheila O. S.', 'Nogueira Neto, Francisco S.', 'Asano, Karen M.', 'Souza, Sibele P.', 'Richtzenhain, Leonardo J.', 'Brandao, Paulo E.']",ScientificWorldJournal,,,True
cc61245f0f1817ac5d96a0cf9bce41377d6e4978,PMC,Detection of Coronaviruses in Bats of Various Species in Italy,http://dx.doi.org/10.3390/v5112679,PMC3856409,24184965,CC BY,"Bats are natural reservoirs for many mammalian coronaviruses, which have received renewed interest after the discovery of the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) CoV in humans. This study describes the identification and molecular characterization of alphacoronaviruses and betacoronaviruses in bats in Italy, from 2010 to 2012. Sixty-nine faecal samples and 126 carcasses were tested using pan-coronavirus RT-PCR. Coronavirus RNAs were detected in seven faecal samples and nine carcasses. A phylogenetic analysis of RNA-dependent RNA polymerase sequence fragments aided in identifying two alphacoronaviruses from Kuhl’s pipistrelle (Pipistrellus kuhlii), three clade 2b betacoronaviruses from lesser horseshoe bats (Rhinolophus hipposideros), and 10 clade 2c betacoronaviruses from Kuhl’s pipistrelle, common noctule (Nyctalus noctula), and Savi’s pipistrelle (Hypsugo savii). This study fills a substantive gap in the knowledge on bat-CoV ecology in Italy, and extends the current knowledge on clade 2c betacoronaviruses with new sequences obtained from bats that have not been previously described as hosts of these viruses.",2013 Oct 31,"['Lelli, Davide', 'Papetti, Alice', 'Sabelli, Cristiano', 'Rosti, Enrica', 'Moreno, Ana', 'Boniotti, Maria B.']",Viruses,,,True
2c5983eedfe4431e007a45dcf0103176ed1d9ff8,PMC,Identification of Three Antiviral Inhibitors against Japanese Encephalitis Virus from Library of Pharmacologically Active Compounds 1280,http://dx.doi.org/10.1371/journal.pone.0078425,PMC3857149,24348901,CC BY,"Japanese encephalitis virus (JEV) can cause severe central nervous disease with a high mortality rate. There is no antiviral drug available for JEV-specific treatment. In this study, a cytopathic-effect-based, high-throughput screening assay was developed and applied to screen JEV inhibitors from Library of Pharmacologically Active Compounds 1280. The antiviral effects of three hit compounds including FGIN-1-27, cilnidipine, and niclosamide were evaluated in cells by western blotting, indirect immunofluorescence assay, and plaque reduction assay. A time-of-addition assay proved that all three compounds inhibited JEV at the stage of replication. The EC50s of FGIN-1-27, cilnidipine, and niclosamide were 3.21, 6.52, and 5.80 µM, respectively, while the selectivity indexes were 38.79, 30.67, and 7.49. FGIN-1-27 and cilnidipine have high efficiency and selectivity against JEV. This study provided two JEV antiviral inhibitors as candidates for treatment of JEV infection.",2013 Nov 4,"[""Fang, Jin'e"", 'Sun, Leqiang', 'Peng, Guiqing', 'Xu, Jia', 'Zhou, Rui', 'Cao, Shengbo', 'Chen, Huanchun', 'Song, Yunfeng']",PLoS One,,,True
4070000cd4a0880ff387df1d1a42f5f45f34e015,PMC,Tmprss2 Is Essential for Influenza H1N1 Virus Pathogenesis in Mice,http://dx.doi.org/10.1371/journal.ppat.1003774,PMC3857797,24348248,CC BY,"Annual influenza epidemics and occasional pandemics pose a severe threat to human health. Host cell factors required for viral spread but not for cellular survival are attractive targets for novel approaches to antiviral intervention. The cleavage activation of the influenza virus hemagglutinin (HA) by host cell proteases is essential for viral infectivity. However, it is unknown which proteases activate influenza viruses in mammals. Several candidates have been identified in cell culture studies, leading to the concept that influenza viruses can employ multiple enzymes to ensure their cleavage activation in the host. Here, we show that deletion of a single HA-activating protease gene, Tmprss2, in mice inhibits spread of mono-basic H1N1 influenza viruses, including the pandemic 2009 swine influenza virus. Lung pathology was strongly reduced and mutant mice were protected from weight loss, death and impairment of lung function. Also, after infection with mono-basic H3N2 influenza A virus body weight loss and survival was less severe in Tmprss2 mutant compared to wild type mice. As expected, Tmprss2-deficient mice were not protected from viral spread and pathology after infection with multi-basic H7N7 influenza A virus. In conclusion, these results identify TMPRSS2 as a host cell factor essential for viral spread and pathogenesis of mono-basic H1N1 and H3N2 influenza A viruses.",2013 Dec 5,"['Hatesuer, Bastian', 'Bertram, Stephanie', 'Mehnert, Nora', 'Bahgat, Mahmoud M.', 'Nelson, Peter S.', 'Pöhlman, Stefan', 'Schughart, Klaus']",PLoS Pathog,,,True
c0cf1c6377c3115aa80ff787332120d4ba1cd386,PMC,Coronaviruses as DNA Wannabes: A New Model for the Regulation of RNA Virus Replication Fidelity,http://dx.doi.org/10.1371/journal.ppat.1003760,PMC3857799,24348241,CC BY,,2013 Dec 5,"['Smith, Everett Clinton', 'Denison, Mark R.']",PLoS Pathog,,,True
9642cb44e010ca78890c7021b2641ad7d3fcdc69,PMC,Data Sharing in a Humanitarian Organization: The Experience of Médecins Sans Frontières,http://dx.doi.org/10.1371/journal.pmed.1001562,PMC3858219,24339750,CC BY,Unni Karunakara and colleagues discuss how Médecins Sans Frontières decided to adopt a data sharing policy for routinely collected clinical and research data in humanitarian settings and its aspirations to create a truly open data set with the first step being managed access. Please see later in the article for the Editors' Summary,2013 Dec 10,"Karunakara, Unni",PLoS Med,,,True
a9e7f41215542f62723e5118535f51d7d0c5cdab,PMC,Plasmablasts as Migratory IgG-Producing Cells in the Pathogenesis of Neuromyelitis Optica,http://dx.doi.org/10.1371/journal.pone.0083036,PMC3858367,24340077,CC BY,"Neuromyelitis optica (NMO) is an inflammatory disease characterized by recurrent attacks of optic neuritis and myelitis. It is generally accepted that autoantibodies against aquaporin 4 water channel protein play a pathogenic role in neuromyelitis optica. We have recently reported that plasmablasts are increased in the peripheral blood of this autoimmune disease, and are capable of producing autoantibodies against aquaporin 4. Here, we demonstrate that CD138(+)HLA-DR(+) plasmablasts, a subset of IgG-producing cells, are increased in the peripheral blood and are enriched among the cerebrospinal fluid (CSF) lymphocytes during the relapse of neuromyelitis optica. Notably, these CD138(+)HLA-DR(+) plasmablasts overexpress CXCR3, whose ligands are present in the cerebrospinal fluid during the relapse of neuromyelitis optica. These results led us to speculate that plasmablasts producing anti-aquaporin 4 autoantibodies might traffic toward the central nervous system (CNS). Furthermore, we performed single-cell sorting of plasmablasts from peripheral blood and CSF samples from NMO and sequenced the complementarity-determining regions (CDRs) of the IgG heavy chain expressed by the sorted plasmablast clones. There were high frequencies of mutations in the CDRs compared with framework regions, indicating that these plasmablast clones would represent a post-germinal center B-cell lineage. Consistent with the preceding results, the plasmablast clones from the peripheral blood shared the same CDR sequences with the clones from the CSF. These results indicate that IgG-producing plasmablasts, which are guided by helper T-cells, may migrate from the peripheral blood preferentially to the CSF. Since migratory plasmablasts could be involved in the inflammatory pathology of NMO, the B-cell subset and their migration might be an attractive therapeutic target.",2013 Dec 10,"['Chihara, Norio', 'Aranami, Toshimasa', 'Oki, Shinji', 'Matsuoka, Takako', 'Nakamura, Masakazu', 'Kishida, Hitaru', 'Yokoyama, Kazumasa', 'Kuroiwa, Yoshiyuki', 'Hattori, Nobutaka', 'Okamoto, Tomoko', 'Murata, Miho', 'Toda, Tatsushi', 'Miyake, Sachiko', 'Yamamura, Takashi']",PLoS One,,,True
5c10b401cc688e4f966e2ab5f41ab3a056685a3d,PMC,The Panhandle Formed by Influenza A and C Virus NS Non-Coding Regions Determines NS Segment Expression,http://dx.doi.org/10.1371/journal.pone.0081550,PMC3858493,24348921,CC BY,"Exchange of the extremities of the NS segment of type A and C influenza viruses in reverse genetics systems was used to assess their putative role in type specificity. Restoration of each specific proximal panhandle was mandatory to allow the rescue of viruses with heterotypic extremities. Moreover, the transcription level of the modified segment seemed to be directly affected by the distal panhandle strength.",2013 Nov 21,"['Crescenzo-Chaigne, Bernadette', 'Barbezange, Cyril', 'van der Werf, Sylvie']",PLoS One,,,True
e5f64cc1c75a45af66bdd08d4d480b8bd70bbe9d,PMC,iEzy-Drug: A Web Server for Identifying the Interaction between Enzymes and Drugs in Cellular Networking,http://dx.doi.org/10.1155/2013/701317,PMC3858977,24371828,CC BY,"With the features of extremely high selectivity and efficiency in catalyzing almost all the chemical reactions in cells, enzymes play vitally important roles for the life of an organism and hence have become frequent targets for drug design. An essential step in developing drugs by targeting enzymes is to identify drug-enzyme interactions in cells. It is both time-consuming and costly to do this purely by means of experimental techniques alone. Although some computational methods were developed in this regard based on the knowledge of the three-dimensional structure of enzyme, unfortunately their usage is quite limited because three-dimensional structures of many enzymes are still unknown. Here, we reported a sequence-based predictor, called “iEzy-Drug,” in which each drug compound was formulated by a molecular fingerprint with 258 feature components, each enzyme by the Chou's pseudo amino acid composition generated via incorporating sequential evolution information and physicochemical features derived from its sequence, and the prediction engine was operated by the fuzzy K-nearest neighbor algorithm. The overall success rate achieved by iEzy-Drug via rigorous cross-validations was about 91%. Moreover, to maximize the convenience for the majority of experimental scientists, a user-friendly web server was established, by which users can easily obtain their desired results.",2013 Nov 26,"['Min, Jian-Liang', 'Xiao, Xuan', 'Chou, Kuo-Chen']",Biomed Res Int,,,False
02ee87386084e0c94d20ad44138ea6488dbd293d,PMC,iEzy-Drug: A Web Server for Identifying the Interaction between Enzymes and Drugs in Cellular Networking,http://dx.doi.org/10.1155/2013/701317,PMC3858977,24371828,CC BY,"With the features of extremely high selectivity and efficiency in catalyzing almost all the chemical reactions in cells, enzymes play vitally important roles for the life of an organism and hence have become frequent targets for drug design. An essential step in developing drugs by targeting enzymes is to identify drug-enzyme interactions in cells. It is both time-consuming and costly to do this purely by means of experimental techniques alone. Although some computational methods were developed in this regard based on the knowledge of the three-dimensional structure of enzyme, unfortunately their usage is quite limited because three-dimensional structures of many enzymes are still unknown. Here, we reported a sequence-based predictor, called “iEzy-Drug,” in which each drug compound was formulated by a molecular fingerprint with 258 feature components, each enzyme by the Chou's pseudo amino acid composition generated via incorporating sequential evolution information and physicochemical features derived from its sequence, and the prediction engine was operated by the fuzzy K-nearest neighbor algorithm. The overall success rate achieved by iEzy-Drug via rigorous cross-validations was about 91%. Moreover, to maximize the convenience for the majority of experimental scientists, a user-friendly web server was established, by which users can easily obtain their desired results.",2013 Nov 26,"['Min, Jian-Liang', 'Xiao, Xuan', 'Chou, Kuo-Chen']",Biomed Res Int,,,False
4b56fb5add2d1264c928b8c0fb39d55c93a814b7,PMC,iEzy-Drug: A Web Server for Identifying the Interaction between Enzymes and Drugs in Cellular Networking,http://dx.doi.org/10.1155/2013/701317,PMC3858977,24371828,CC BY,"With the features of extremely high selectivity and efficiency in catalyzing almost all the chemical reactions in cells, enzymes play vitally important roles for the life of an organism and hence have become frequent targets for drug design. An essential step in developing drugs by targeting enzymes is to identify drug-enzyme interactions in cells. It is both time-consuming and costly to do this purely by means of experimental techniques alone. Although some computational methods were developed in this regard based on the knowledge of the three-dimensional structure of enzyme, unfortunately their usage is quite limited because three-dimensional structures of many enzymes are still unknown. Here, we reported a sequence-based predictor, called “iEzy-Drug,” in which each drug compound was formulated by a molecular fingerprint with 258 feature components, each enzyme by the Chou's pseudo amino acid composition generated via incorporating sequential evolution information and physicochemical features derived from its sequence, and the prediction engine was operated by the fuzzy K-nearest neighbor algorithm. The overall success rate achieved by iEzy-Drug via rigorous cross-validations was about 91%. Moreover, to maximize the convenience for the majority of experimental scientists, a user-friendly web server was established, by which users can easily obtain their desired results.",2013 Nov 26,"['Min, Jian-Liang', 'Xiao, Xuan', 'Chou, Kuo-Chen']",Biomed Res Int,,,False
338ea249f053b957f0681c987b83322a96a7350b,PMC,iEzy-Drug: A Web Server for Identifying the Interaction between Enzymes and Drugs in Cellular Networking,http://dx.doi.org/10.1155/2013/701317,PMC3858977,24371828,CC BY,"With the features of extremely high selectivity and efficiency in catalyzing almost all the chemical reactions in cells, enzymes play vitally important roles for the life of an organism and hence have become frequent targets for drug design. An essential step in developing drugs by targeting enzymes is to identify drug-enzyme interactions in cells. It is both time-consuming and costly to do this purely by means of experimental techniques alone. Although some computational methods were developed in this regard based on the knowledge of the three-dimensional structure of enzyme, unfortunately their usage is quite limited because three-dimensional structures of many enzymes are still unknown. Here, we reported a sequence-based predictor, called “iEzy-Drug,” in which each drug compound was formulated by a molecular fingerprint with 258 feature components, each enzyme by the Chou's pseudo amino acid composition generated via incorporating sequential evolution information and physicochemical features derived from its sequence, and the prediction engine was operated by the fuzzy K-nearest neighbor algorithm. The overall success rate achieved by iEzy-Drug via rigorous cross-validations was about 91%. Moreover, to maximize the convenience for the majority of experimental scientists, a user-friendly web server was established, by which users can easily obtain their desired results.",2013 Nov 26,"['Min, Jian-Liang', 'Xiao, Xuan', 'Chou, Kuo-Chen']",Biomed Res Int,,,True
c4e99c8b861f4457b4a0518860bc9e52f5348e87,PMC,Zoos through the Lens of the IUCN Red List: A Global Metapopulation Approach to Support Conservation Breeding Programs,http://dx.doi.org/10.1371/journal.pone.0080311,PMC3859473,24348999,CC BY,"Given current extinction trends, the number of species requiring conservation breeding programs (CBPs) is likely to increase dramatically. To inform CBP policies for threatened terrestrial vertebrates, we evaluated the number and representation of threatened vertebrate species on the IUCN Red List held in the ISIS zoo network and estimated the complexity of their management as metapopulations. Our results show that 695 of the 3,955 (23%) terrestrial vertebrate species in ISIS zoos are threatened. Only two of the 59 taxonomic orders show a higher proportion of threatened species in ISIS zoos than would be expected if species were selected at random. In addition, for most taxa, the management of a zoo metapopulation of more than 250 individuals will require the coordination of a cluster of 11 to 24 ISIS zoos within a radius of 2,000 km. Thus, in the zoo network, the representation of species that may require CBPs is currently low and the spatial distribution of these zoo populations makes management difficult. Although the zoo community may have the will and the logistical potential to contribute to conservation actions, including CBPs, to do so will require greater collaboration between zoos and other institutions, alongside the development of international agreements that facilitate cross-border movement of zoo animals. To maximize the effectiveness of integrated conservation actions that include CBPs, it is fundamental that the non-zoo conservation community acknowledges and integrates the expertise and facilities of zoos where it can be helpful.",2013 Dec 11,"['Conde, Dalia A.', 'Colchero, Fernando', 'Gusset, Markus', 'Pearce-Kelly, Paul', 'Byers, Onnie', 'Flesness, Nate', 'Browne, Robert K.', 'Jones, Owen R.']",PLoS One,,,True
cf7837069ab6a12d5663c6f3c715b73fe53493a1,PMC,Cellular microRNA miR-181b Inhibits Replication of Mink Enteritis Virus by Repression of Non-Structural Protein 1 Translation,http://dx.doi.org/10.1371/journal.pone.0081515,PMC3859502,24349084,CC BY,"Mink enteritis virus (MEV) is one of the most important viral pathogens in the mink industry. Recent studies have showed that microRNAs (miRNAs), small noncoding RNAs of length ranging from 18–23 nucleotides (nt) participate in host-pathogen interaction networks; however, whether or not miRNAs are involved in MEV infection has not been reported. Our study revealed that miRNA miR-181b inhibited replication of MEV in the feline kidney (F81) cell line by targeting the MEV non-structural protein 1 (NS1) messenger RNA (mRNA) coding region, resulting in NS1 translational repression, while MEV infection reduced miR-181b expression. This is the first description of cellular miRNAs modulating MEV infection in F81 cells, providing further insight into the mechanisms of viral infection, and may be useful in development of naturally-occurring miRNAs antiviral strategies.",2013 Dec 11,"['Sun, Jia-zeng', 'Wang, Jigui', 'Yuan, Daoli', 'Wang, Shuang', 'Li, Zhili', 'Yi, Bao', 'Mao, Yaping', 'Hou, Qiang', 'Liu, Weiquan']",PLoS One,,,True
3c440b07b2bc59e8483537e994bbd7ac0030801a,PMC,A Leaderless Genome Identified during Persistent Bovine Coronavirus Infection Is Associated with Attenuation of Gene Expression,http://dx.doi.org/10.1371/journal.pone.0082176,PMC3861326,24349214,CC BY,"The establishment of persistent viral infection is often associated with the selection of one or more mutant viruses. For example, it has been found that an intraleader open reading frame (ORF) in genomic and subgenomic mRNA (sgmRNA) molecules is selected during bovine coronavirus (BCoV) persistence which leads to translation attenuation of the downstream ORF. Here, we report the unexpected identification of leaderless genomes, in addition to leader-containing genomes, in a cell culture persistently infected with BCoV. The discovery was made by using a head-to-tail ligation method that examines genomic 5′-terminal sequences at different times postinfection. Functional analyses of the leaderless genomic RNA in a BCoV defective interfering (DI) RNA revealed that (1) the leaderless genome was able to serve as a template for the synthesis of negative-strand genome, although it cannot perform replicative positive-strand genomic RNA synthesis, and (2) the leaderless genome retained its function in translation and transcription, although the efficiency of these processes was impaired. Therefore, this previously unidentified leaderless genome is associated with the attenuation of genome expression. Whether the leaderless genome contributes to the establishment of persistent infection remains to be determined.",2013 Dec 12,"['Ke, Ting-Yung', 'Liao, Wei-Yu', 'Wu, Hung-Yi']",PLoS One,,,True
4ee2232fd9b2088955ad781243f135dc76edbaf1,PMC,Endoplasmic Reticulum Stress Contributes to Helicobacter Pylori VacA-Induced Apoptosis,http://dx.doi.org/10.1371/journal.pone.0082322,PMC3862672,24349255,CC0,"Vacuolating cytotoxin A (VacA) is one of the important virulence factors produced by H. pylori. VacA induces apoptotic cell death, which is potentiated by ammonia. VacA also causes cell death by mitochondrial damage, via signaling pathways that are not fully defined. Our aim was to determine whether endoplasmic reticulum (ER) stress is associated with VacA-induced mitochondrial dysfunction and apoptosis. We found that C/EBP homologous protein (CHOP), a key signaling protein of ER stress-induced apoptosis, was transcriptionally up-regulated following incubation of gastric epithelial cells with VacA. The effect of VacA on CHOP induction was significantly enhanced by co-incubation with ammonium chloride. Phosphorylation of eukaryotic initiation factor 2 (eIF2)-alpha, which is known to occur downstream of the ER stress sensor PKR-like ER-localized eIF2-alpha kinase (PERK) and to regulate CHOP expression, was also observed following incubation with VacA in the presence of ammonium chloride. Knockdown of CHOP by siRNA resulted in inhibition of VacA-induced apoptosis. Further studies showed that silencing of the PERK gene with siRNA attenuated VacA-mediated phosphorylation of eIF2-alpha, CHOP induction, expression of BH3-only protein Bim and Bax activation, and cell death induced by VacA with ammonium chloride, indicating that ER stress may lead to mitochondrial dysfunction during VacA-induced toxicity. Activation of ER stress and up-regulation of BH3-only proteins were also observed in human H. pylori-infected gastric mucosa. Collectively, this study reveals a possible association between VacA-induced apoptosis in gastric epithelial cells, and activation of ER stress in H. pylori-positive gastric mucosa.",2013 Dec 13,"['Akazawa, Yuko', 'Isomoto, Hajime', 'Matsushima, Kayoko', 'Kanda, Tsutomu', 'Minami, Hitomi', 'Yamaghchi, Naoyuki', 'Taura, Naota', 'Shiozawa, Ken', 'Ohnita, Ken', 'Takeshima, Fuminao', 'Nakano, Masayuki', 'Moss, Joel', 'Hirayama, Toshiya', 'Nakao, Kazuhiko']",PLoS One,,,True
5d46c99fa67d9b839724a7349e6ffb22ba71cf1d,PMC,"Surveillance, response systems, and evidence updates on emerging zoonoses: the role of one health",http://dx.doi.org/10.3402/iee.v3i0.21386,PMC3864162,24363836,CC BY,"Globally, emerging zoonotic diseases are increasing. Existing surveillance systems for zoonoses have substantial gaps, especially in developing countries, and the systems in place in the developed world require improvements. Resources and updates on evidence-based practice (EBP) for zoonoses are sparser in the veterinary literature as compared to the medical literature. Evidence updates for emerging zoonoses are either absent or rudimentary in both human and veterinary medicine. A ‘one-health’ concept, including a global signaling surveillance system for emerging zoonoses, will be essential for correct diagnoses, interventions, and public health strategies. An open access EBP platform supported by builders of EBP resources is urgently needed to counter emerging zoonoses.",2013 Dec 13,"['Asokan, G. V.', 'Kasimanickam, Ramanathan K.', 'Asokan, Vanitha']",Infect Ecol Epidemiol,,,True
046a56d635edc933ed8f30ccf1ae9fd488dfe645,PMC,Tat Peptide-Mediated Soluble Expression of the Membrane Protein LSECtin-CRD in Escherichia coli,http://dx.doi.org/10.1371/journal.pone.0083579,PMC3865297,24358298,CC BY,"The human liver and lymph node sinusoidal endothelial cell C-type lectin (hLSECtin), a type II integral membrane protein, containing a Ca(2+)-dependent carbohydrate recognition domain (CRD), has a well-established biological activity, yet its three-dimensional structure is unknown due to low expression yields and aggregation into inclusion bodies. Previous study has demonstrated that the HIV-1 virus-encoded Tat peptide (‘YGRKKRRQRRR’) can increase the yields and the solubility of heterologous proteins. However, whether the Tat peptide could promote the high-yield and soluble expression of membrane proteins in Escherichia coli is not known. Therefore, the prokaryotic expression vector pET28b-Tat-hLSECtin-CRD (using pET28b and pET28b-hLSECtin-CRD as controls) was constructed, and transformed into E. coli BL21 (DE3) cells and induced with isopropyl-β-d-thiogalactoside (IPTG) followed with identifying by SDS-PAGE and Western blot. Subsequently, the bacterial subcellular structure, in which overexpressed the heterologous proteins Tat-hLSECtin-CRD and Tat-free hLSECtin-CRD, was analyzed by transmission electron microscope (TEM) respectively, and the mannose-binding activity of Tat-hLSECtin-CRD was also determined. Expectedly, the solubility of Tat-LSECtin-CRD significantly increased compared to Tat-free LSECtin-CRD (**p < 0.01) with prolonged time, and the Tat-LSECtin-CRD had a significant mannose-binding activity. The subcellular structure analysis indicated that the bacterial cells overexpressed Tat-hLSECtin-CRD exhibited denser region compared with controls, while dot denser region aggregated in the two ends of bacterial cells overexpressed Tat-free hLSECtin-CRD. This study provided a novel method for improving the soluble expression of membrane proteins in prokaryotic systems by fusion with the Tat peptide, which may be potentially expanded to the expression of other membrane proteins.",2013 Dec 16,"['Dong, Guofu', 'Wang, Changzhen', 'Wu, Yonghong', 'Cong, Jianbo', 'Cheng, Li', 'Wang, Mingqun', 'Zhao, Pengkai', 'Tang, Li', 'Zhang, Chenggang', 'Wu, Ke']",PLoS One,,,True
83f5dbddb15c7cc6ad9d27d00ba1226462845440,PMC,Antisense suppression of donor splice site mutations in the dystrophin gene transcript,http://dx.doi.org/10.1002/mgg3.19,PMC3865583,24498612,CC BY,"We describe two donor splice site mutations, affecting dystrophin exons 16 and 45 that led to Duchenne muscular dystrophy (DMD), through catastrophic inactivation of the mRNA. These gene lesions unexpectedly resulted in the retention of the downstream introns, thereby increasing the length of the dystrophin mRNA by 20.2 and 36 kb, respectively. Splice-switching antisense oligomers targeted to exon 16 excised this in-frame exon and the following intron from the patient dystrophin transcript very efficiently in vitro, thereby restoring the reading frame and allowing synthesis of near-normal levels of a putatively functional dystrophin isoform. In contrast, targeting splice-switching oligomers to exon 45 in patient cells promoted only modest levels of an out-of-frame dystrophin transcript after transfection at high oligomer concentrations, whereas dual targeting of exons 44 and 45 or 45 and 46 resulted in more efficient exon skipping, with concomitant removal of intron 45. The splice site mutations reported here appear highly amenable to antisense oligomer intervention. We suggest that other splice site mutations may need to be evaluated for oligomer interventions on a case-by-case basis.",2013 Sep 13,"['Fletcher, Sue', 'Meloni, Penny L', 'Johnsen, Russell D', 'Wong, Brenda L', 'Muntoni, Francesco', 'Wilton, Stephen D']",Mol Genet Genomic Med,,,True
4300be597ccbea9acb374312063e2776b7f631c4,PMC,"Epidemiology of Human Respiratory Viruses in Children with Acute Respiratory Tract Infections in Jinan, China",http://dx.doi.org/10.1155/2013/210490,PMC3865640,24363757,CC BY,"The viral etiologies of UTRIs and LTRIs in children in Jinan city were investigated between July 2009 and June 2010. Nasal and throat swabs were collected from 397 children with URTIs and bronchoalveolar lavage fluid specimens were collected from 323 children with LRTIs. RT-PCR/PCR was used to examine all samples for IFV, PIV, RSV, RV, hMPV, HBoV, CoV, ADV, RSV, and EV. Viral pathogens were detected in 47.10% of URTI samples and 66.57% samples, and the incidence of viral coinfection was 5.29% and 21.05%, respectively. IFV was the most common virus in URTIs, with a detection rate of 19.40%, followed by PIV (10.83%), RV (10.58%), and EV (6.30%). For LRTIs, PIV and RV were both detected in 27% of samples, followed by RSV (9.91%), HBoV (8.36%), IFV (5.57%), and hMPV (5.57%). RSV and HBoV were more prevalent in the youngest children of no more than six months. Meanwhile, RV, PIV, and RSV were the most frequent viruses combined with bacterial pathogens in LRTIs. In conclusion, the spectrum of respiratory virus infections in URTIs and LRTIs differed in terms of the most common pathogens, seasonal distribution, and coinfection rate.",2013 Dec 2,"['Lu, Yanqin', 'Wang, Shifu', 'Zhang, Lehai', 'Xu, Chao', 'Bian, Cuirong', 'Wang, Zhaoxia', 'Ma, Yanhui', 'Wang, Ke', 'Ma, Lixia', 'Meng, Chen', 'Ni, Caiyun', 'Tong, Jiabei', 'Li, Gongchao', 'Han, Jinxiang']",Clin Dev Immunol,,,True
88249503fb8dd13282a60ceac441edd59e1c5be3,PMC,Glucocorticosteroid in Treatment of Severe Pneumonia,http://dx.doi.org/10.1155/2013/865635,PMC3865735,24363503,CC BY,"Airway diseases such as pneumonia constitute a major health burden on a global scale; untreated pneumonia may develop to severe pneumonia and consequently lead to to fatal episodes of mortality and morbidity. The balance between inflammatory mediators is key for the outcome of the pulmonary infection; elimination of invading pathogen was marked by the release of cytokines and other inflammatory mediators from alveolar macrophages and glucocorticoid steroids (GCs) acting on the inflammatory component. Treatments of severe pneumonia with GCs have been developing for years with inconclusive results. In many cases GCs have been administered empirically without clinical evidence. Recent studies assess beneficial impact on treatment of severe pneumonia by suggesting specific dosage, period of administration, and tapered dosage.",2013 Dec 2,"['Ariani, Felinda', 'Liu, Kaixiong', 'Jing, Zhang', 'Qu, Jieming']",Mediators Inflamm,,,True
c9bcd70bf18a413b1af105124cc232f2fe0fd5b9,PMC,A Replicating Modified Vaccinia Tiantan Strain Expressing an Avian-Derived Influenza H5N1 Hemagglutinin Induce Broadly Neutralizing Antibodies and Cross-Clade Protective Immunity in Mice,http://dx.doi.org/10.1371/journal.pone.0083274,PMC3866202,24358269,CC BY,"To combat the possibility of a zoonotic H5N1 pandemic in a timely fashion, it is necessary to develop a vaccine that would confer protection against homologous and heterologous human H5N1 influenza viruses. Using a replicating modified vaccinia virus Tian Tan strain (MVTT) as a vaccine vector, we constructed MVTT(HA-QH) and MVTT(HA-AH), which expresses the H5 gene of a goose-derived Qinghai strain A/Bar-headed Goose/Qinghai/1/2005 or human-derived Anhui Strain A/Anhui/1/2005. The immunogenicity profiles of both vaccine candidates were evaluated. Vaccination with MVTT(HA-QH) induced a significant level of neutralizing antibodies (Nabs) against a homologous strain and a wide range of H5N1 pseudoviruses (clades 1, 2.1, 2.2, 2.3.2, and 2.3.4). Neutralization tests (NT) and Haemagglutination inhibition (HI) antibodies inhibit the live autologous virus as well as a homologous A/Xingjiang/1/2006 and a heterologous A/Vietnam/1194/2004, representing two human isolates from clade 2.2 and clade 1, respectively. Importantly, mice vaccinated with intranasal MVTT(HA-QH) were completely protected from challenge with lethal dosages of A/Bar-headed Goose/Qinghai/1/2005 and the A/Viet Nam/1194/2004, respectively, but not control mice that received a mock MVTT(S) vaccine. However, MVTT(HA-AH) induced much lower levels of NT against its autologous strain. Our results suggest that it is feasible to use the H5 gene from A/Bar-headed Goose/Qinghai/1/2005 to construct an effective vaccine, when using MVTT as a vector, to prevent infections against homologous and genetically divergent human H5N1 influenza viruses.",2013 Dec 17,"['Xiao, Haixia', 'Liu, Li', 'Zhu, Qingyu', 'Tan, Zhiwu', 'Yu, Wenbo', 'Tang, Xian', 'Zhan, Dawei', 'Du, Yanhua', 'Wang, Haibo', 'Liu, Di', 'Li, Zhixin', 'Yuen, Kwok-Yung', 'Ho, David D.', 'Gao, George F.', 'Chen, Zhiwei']",PLoS One,,,True
e9b3af3ad2b2abfacc4228e0ae590cc645f29718,PMC,Application of an Amine Functionalized Biopolymer in the Colonic Delivery of Glycyrrhizin: A Design and In Vivo Efficacy Study,http://dx.doi.org/10.3797/scipharm.1301-14,PMC3867243,24482776,CC BY,"In our current study, a newer amine functionalized guar gum derivative was studied for its efficacy in colonic drug delivery. Glycyrrhizic acid mono-ammonium salt was used as the model drug. Drug-loaded microparticles were formulated by ionic crosslinking using sodium tripolyphosphate. The Scanning Electron Microscopic study revealed spherical particles of sizes from 4.9 ± 3.8 μm to 6.9 ± 3.9 μm. The FT-IR studies presented a possible interaction between the drug and the polymer. The drug was encapsulated in amorphous form as observed from the powder X-Ray Diffraction studies. A cumulative drug release study was carried out in simulated gastric, intestinal, and colonic fluids. The cumulative drug release studies presented a burst release followed by a sustained release of the drug in simulated colonic fluid containing rat cecal contents. The drug-polymer ratio was optimised using a 3(2) factorial design by taking the amounts of glycyrrhizic acid (X(1)) and guar gum alkyl amine (X(2)) as the independant variables. The percent cumulative drug release at 240 mins (Q(240)), 720 mins (Q(720)), and at 1,440 mins (Q(1440)) were considered as the dependant variables. The efficacy of the optimized formulation was studied in a 2,4,6-trinitrobenzene sulfonic acid-induced rat colitis model. The tissue’s nitric oxide, malondialdehyde, and myeloperoxidase activities were found to be much lower in the microparticle-treated group compared to free drug-treated group. The histology of the colonic tissue from the treated group of animals revealed almost no infiltration of inflammatory cells in the tissue for the microparticle-treated group of animals. The synthesized amine derivative of guar gum was found to be better in vitro with a better in vivo efficacy in the colonic delivery of glycyrrhizic acid monoammonium salt and can be considered as a newer modified biopolymer for colonic drug delivery.",2013 May 18 Oct-Dec,"['Kumar De, Amit', 'Datta, Sriparna', 'Mukherjee, Arup']",Sci Pharm,,,True
5159ab148faaafed700258c0a6278cb1fb5476e7,PMC,"Characterization of the Complete Genome of Chikungunya in Zhejiang, China, Using a Modified Virus Discovery Method Based on cDNA-AFLP",http://dx.doi.org/10.1371/journal.pone.0083014,PMC3867435,24367579,CC BY,"BACKGROUND: Chikungunya (CHIK) virus is a mosquito-borne emerging pathogen presenting great health challenges worldwide, particularly in tropical zones. Here we report a newly detected strain of CHIK, Zhejiang/chik-sy/2012, in China, a nonindigenous region for CHIK, using a modified approach based on the classic cDNA-AFLP. We then performed etiological and phylogenetic analyses to better understand its molecular characterization and phylogenetic pattern, and also to aid in further evaluating its persistence in Southeast Asia. METHODS: By using this modified procedure, we determined for the first time the complete genome sequence of the chikungunya virus strain, Zhejiang/chik-sy/2012, isolated in 2012 from a patient in Zhejiang, China. Sequence analyses revealed that this positive single strand of RNA is 12,017 bp long. We found no single amino acid mutation in A226V, D284E and A316V. Phylogenetic analysis showed that our strain shared the greatest homology with a strain isolated in Taiwan, which was derived from a strain from Indonesia. Chik-sy/2012 is in a different clade from other CHIK viruses found in China previously. CONCLUSIONS: A modified cDNA-AFLP in virus discovery was used to isolate the first CHIK and the first complete genome sequence of virus strain chik-sy/2012 in 2012 from a patient with CHIK fever in Zhejiang, China. The infection displayed great phylogenetic distance from viruses detected in Guangdong, China, in 2008 and 2010, since they were derived from another evolutionary lineage. Additional molecular epidemiology data are needed to further understand, monitor and evaluate CHIK in China.",2013 Dec 18,"['Sun, Yi', 'Yan, JuYing', 'Mao, HaiYan', 'Zhang, Lei', 'Lyu, QinFeng', 'Wu, ZhongHua', 'Zheng, Wei', 'Feng, Cen', 'Zhang, YanJun']",PLoS One,,,True
d6f350fa81730f8476614ffe7280454633d77f31,PMC,"The Cytokine and Chemokine Profiles in Patients with Hand, Foot and Mouth Disease of Different Severities in Shanghai, China, 2010",http://dx.doi.org/10.1371/journal.pntd.0002599,PMC3868519,24367714,CC BY,"BACKGROUND AND PURPOSE: Systemic upregulation of inflammatory cytokines is characteristic of critical severe hand, foot, and mouth disease (HFMD) with pulmonary edema. Thus, immunomodulatory medicines such as steroids, including methylprednisolone, have been proposed to treat patients with severe HFMD in China, because it is postulated that inflammatory cytokines play a role in the development of severe complications. This study is to further investigate the inflammatory response in the relatively mild HFMD patients, and whether steroid treatment has a beneficial effect on the suppression of inflammation in HFMD patients. METHOD: We measured the levels of 50 kinds of chemokines, cytokines, growth factors and soluble receptors in serum samples from control patients without HFMD and the HFMD patients with or without prior treatment of intravenous methylprednisolone. RESULTS: Our present study found that even relatively mild HFMD patients without central nervous system (CNS) complications had elevated serum levels of inflammatory cytokines, including interleukin (IL)-3, IL-6, IL-12p40, and tumor necrosis factor (TNF)-α, which suggested systemic inflammation. In contrast, these patients also have decreased levels of other serum biomarkers, including IL-1Ra, IL-8, IL-16, soluble ICAM-1, CXCL-1, and CCL27. The dysregulation of cytokine and chemokine expression may be involved in CNS complications and unbalanced circulating leukocytes in HFMD patients. Surprisingly, patients treated with methylprednisolone had no difference in the expression levels of HFMD-associated biomarkers instead had slightly increased levels of IL-17A, which was not associated with the occurrence of HFMD. CONCLUSION: Whether steroid treatment has any beneficial effect on the prognosis of HFMD patients requires to be further investigated.",2013 Dec 19,"['Zeng, Mei', 'Zheng, Xiaoyan', 'Wei, Ruicheng', 'Zhang, Na', 'Zhu, Kai', 'Xu, Bin', 'Yang, Chun-Hui', 'Yang, Chun-Fu', 'Deng, Chaoyang', 'Pu, Dongbo', 'Wang, Xiaohong', 'Altmeyer, Ralf', 'Leng, Qibin']",PLoS Negl Trop Dis,,,True
2be4d8ed799f2556c53e6946720e3033d41060e2,PMC,"Space-Time Clustering Characteristics of Tuberculosis in China, 2005-2011",http://dx.doi.org/10.1371/journal.pone.0083605,PMC3868653,24367604,CC BY,"OBJECTIVES: China is one of the 22 tuberculosis (TB) high-burden countries in the world. As TB is a major public health problem in China, spatial analysis could be applied to detect geographic distribution of TB clusters for targeted intervention on TB epidemics. METHODS: Spatial analysis was applied for detecting TB clusters on county-based TB notification data in the national notifiable infectious disease case reporting surveillance system from 2005 to 2011. Two indicators of TB epidemic were used including new sputum smear-positive (SS+) notification rate and total TB notification rate. Global Moran’s I by ArcGIS was used to assess whether TB clustering and its trend were significant. SaTScan software that used the retrospective space-time analysis and Possion probability model was utilized to identify geographic areas and time period of potential clusters with notification rates on county-level from 2005 to 2011. RESULTS: Two indicators of TB notification had presented significant spatial autocorrelation globally each year (p<0.01). Global Moran’s I of total TB notification rate had positive trend as time went by (t=6.87, p<0.01). The most likely clusters of two indicators had similar spatial distribution and size in the south-central regions of China from 2006 to 2008, and the secondary clusters in two regions: northeastern China and western China. Besides, the secondary clusters of total TB notification rate had two more large clustering centers in Inner Mongolia, Gansu and Qinghai provinces and several smaller clusters in Shanxi, Henan, Hebei and Jiangsu provinces. CONCLUSION: The total TB notification cases clustered significantly in some special areas each year and the clusters trended to aggregate with time. The most-likely and secondary clusters that overlapped among two TB indicators had higher TB burden and risks of TB transmission. These were the focused geographic areas where TB control efforts should be prioritized.",2013 Dec 19,"['Zhao, Fei', 'Cheng, Shiming', 'He, Guangxue', 'Huang, Fei', 'Zhang, Hui', 'Xu, Biao', 'Murimwa, Tonderayi C.', 'Cheng, Jun', 'Hu, Dongmei', 'Wang, Lixia']",PLoS One,,,True
81d0bac38646d309a178010b68ebf0e11d43101c,PMC,NEWS,http://dx.doi.org/10.7189/jogh.03.020202,PMC3868822,,CC BY,,2013 Dec,,J Glob Health,,,False
35d8d53b4907862f8ad0c6f72e6905204d4c9562,PMC,Full-Length Genome Sequence of a Plaque-Cloned Virulent Porcine Epidemic Diarrhea Virus Isolate (USA/Iowa/18984/2013) from a Midwestern U.S. Swine Herd,http://dx.doi.org/10.1128/genomeA.01049-13,PMC3868854,24356830,CC BY,Porcine epidemic diarrhea (PED) was recognized in U.S. swine for the first time in early 2013. A plaque-purified PED virus (PEDV) isolate (USA/Iowa/18984/2013) was obtained from a diarrheic piglet. The isolate is genetically close to other previously reported U.S. PEDVs and recent Chinese PEDVs and was virulent when inoculated into neonatal pigs.,2013 Dec 19,"['Hoang, Hai', 'Killian, Mary L.', 'Madson, Darin M.', 'Arruda, Paulo H. E.', 'Sun, Dong', 'Schwartz, Kent J.', 'Yoon, Kyoungjin J.']",Genome Announc,,,True
b94abc8c5e511d49e02cc4175cccc27629f5ee76,PMC,Transcriptome analysis of chicken kidney tissues following coronavirus avian infectious bronchitis virus infection,http://dx.doi.org/10.1186/1471-2164-14-743,PMC3870970,24168272,CC BY,"BACKGROUND: Infectious bronchitis virus (IBV), a prototype of the Coronaviridae family, is an economically important causative agent of infectious bronchitis in chickens and causes an acute and highly contagious upper respiratory tract infections that may lead to nephritis. However, the molecular antiviral mechanisms of chickens to IBV infection remain poorly understood. In this study, we conducted global gene expression profiling of chicken kidney tissue after nephropathogenic IBV infection to better understand the interactions between host and virus. RESULTS: IBV infection contributed to differential expression of 1777 genes, of which 876 were up-regulated and 901 down-regulated in the kidney compared to those of control chickens and 103 associated with immune and inflammatory responses may play important roles in the host defense response during IBV infection. Twelve of the altered immune-related genes were confirmed by real-time RT-PCR. Gene ontology category, KEGG pathway, and gene interaction networks (STRING analysis) were analyzed to identify relationships among differentially expressed genes involved in signal transduction, cell adhesion, immune responses, apoptosis regulation, positive regulation of the I-kappaB kinase/NF-kappaB cascade and response to cytokine stimulus. Most of these genes were related and formed a large network, in which IL6, STAT1, MYD88, IRF1 and NFKB2 were key genes. CONCLUSIONS: Our results provided comprehensive knowledge regarding the host transcriptional response to IBV infection in chicken kidney tissues, thereby providing insight into IBV pathogenesis, particularly the involvement of innate immune pathway genes associated with IBV infection.",2013 Oct 30,"['Cong, Feng', 'Liu, Xiaoli', 'Han, Zongxi', 'Shao, Yuhao', 'Kong, Xiangang', 'Liu, Shengwang']",BMC Genomics,,,True
11227aa67f131d1b8220d5c45b4bf592f0a48ef4,PMC,The discovery and identification of a candidate proteomic biomarker of active tuberculosis,http://dx.doi.org/10.1186/1471-2334-13-506,PMC3870977,24168695,CC BY,"BACKGROUND: Noninvasive and convenient biomarkers for early diagnosis of tuberculosis (TB) remain an urgent need. The aim of this study was to discover and identify potential biomarkers specific for TB. METHODS: The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from 180 cases of TB and 211 control subjects. A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by reverse phase-high performance liquid chromatography (RP-HPLC), identified by MALDI-TOF MS, LC-MS/MS and validated using enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 35 discriminating m/z peaks were detected that were related to TB (P < 0.01). The model of biomarkers based on the four biomarkers (2554.6, 4824.4, 5325.7, and 8606.8 Da) was established which could distinguish TB from controls with the sensitivity of 83.3% and the specificity of 84.2%. The candidate biomarker with m/z of 2554.6 Da was found to be up-regulated in TB patients, and was identified as a fragment of fibrinogen, alpha polypeptide isoform alpha-E preproprotein. Analysis in 22 patients with TB showed increased fibrinogen degradation product (FDP) (5,005 ± 1,297 vs. 4,010 ± 1,181 ng/mL, P < 0.05) and in 142 patients showed elevated plasma fibrinogen levels. CONCLUSIONS: A diagnostic model for TB with high sensitivity and specificity was developed using mass spectrometry combined with magnetic beads. Fibrinogen was identified as a potential biomarker for TB and showed diagnostic values in clinical application.",2013 Oct 29,"['Liu, Jiyan', 'Jiang, Tingting', 'Wei, Liliang', 'Yang, Xiuyun', 'Wang, Chong', 'Zhang, Xing', 'Xu, Dandan', 'Chen, Zhongliang', 'Yang, Fuquan', 'Li, Ji-Cheng']",BMC Infect Dis,,,True
9f824ee0252ae66915b8dc9b593366f921b6d615,PMC,The discovery and identification of a candidate proteomic biomarker of active tuberculosis,http://dx.doi.org/10.1186/1471-2334-13-506,PMC3870977,24168695,CC BY,"BACKGROUND: Noninvasive and convenient biomarkers for early diagnosis of tuberculosis (TB) remain an urgent need. The aim of this study was to discover and identify potential biomarkers specific for TB. METHODS: The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from 180 cases of TB and 211 control subjects. A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by reverse phase-high performance liquid chromatography (RP-HPLC), identified by MALDI-TOF MS, LC-MS/MS and validated using enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 35 discriminating m/z peaks were detected that were related to TB (P < 0.01). The model of biomarkers based on the four biomarkers (2554.6, 4824.4, 5325.7, and 8606.8 Da) was established which could distinguish TB from controls with the sensitivity of 83.3% and the specificity of 84.2%. The candidate biomarker with m/z of 2554.6 Da was found to be up-regulated in TB patients, and was identified as a fragment of fibrinogen, alpha polypeptide isoform alpha-E preproprotein. Analysis in 22 patients with TB showed increased fibrinogen degradation product (FDP) (5,005 ± 1,297 vs. 4,010 ± 1,181 ng/mL, P < 0.05) and in 142 patients showed elevated plasma fibrinogen levels. CONCLUSIONS: A diagnostic model for TB with high sensitivity and specificity was developed using mass spectrometry combined with magnetic beads. Fibrinogen was identified as a potential biomarker for TB and showed diagnostic values in clinical application.",2013 Oct 29,"['Liu, Jiyan', 'Jiang, Tingting', 'Wei, Liliang', 'Yang, Xiuyun', 'Wang, Chong', 'Zhang, Xing', 'Xu, Dandan', 'Chen, Zhongliang', 'Yang, Fuquan', 'Li, Ji-Cheng']",BMC Infect Dis,,,False
871bb1d475d0dbb910cce25e16d066adf9706a4c,PMC,"Functional Limitations of Plasmacytoid Dendritic Cells Limit Type I Interferon, T Cell Responses and Virus Control in Early Life",http://dx.doi.org/10.1371/journal.pone.0085302,PMC3871569,24376875,CC BY,"Infant mortality from viral infection remains a major global health concern: viruses causing acute infections in immunologically mature hosts often follow a more severe course in early life, with prolonged or persistent viral replication. Similarly, the WE strain of lymphocytic choriomeningitis virus (LCMV-WE) causes acute self-limiting infection in adult mice but follows a protracted course in infant animals, in which LCMV-specific CD8(+) T cells fail to expand and control infection. By disrupting type I IFNs signaling in adult mice or providing IFN-α supplementation to infant mice, we show here that the impaired early life T cell responses and viral control result from limited early type I IFN responses. We postulated that plasmacytoid dendritic cells (pDC), which have been identified as one major source of immediate-early IFN-I, may not exert adult-like function in vivo in the early life microenvironment. We tested this hypothesis by studying pDC functions in vivo during LCMV infection and identified a coordinated downregulation of infant pDC maturation, activation and function: despite an adult-like in vitro activation capacity of infant pDCs, the expression of the E2-2 pDC master regulator (and of critical downstream antiviral genes such as MyD88, TLR7/TLR9, NF-κB, IRF7 and IRF8) is downregulated in vivo at baseline and during LCMV infection. A similar pattern was observed in response to ssRNA polyU, a model ligand of the TLR7 viral sensor. This suggests that the limited T cell-mediated defense against early life viral infections is largely attributable to / regulated by infant pDC responses and provides incentives for novel strategies to supplement or stimulate immediate-early IFN-α responses.",2013 Dec 23,"['Belnoue, Elodie', 'Fontannaz, Paola', 'Rochat, Anne-Françoise', 'Tougne, Chantal', 'Bergthaler, Andreas', 'Lambert, Paul-Henri', 'Pinschewer, Daniel D.', 'Siegrist, Claire-Anne']",PLoS One,,,True
8762daff0f7890b72f611247c1a15133ea291afb,PMC,"Recent Advances in Diagnosis, Prevention, and Treatment of Human Respiratory Syncytial Virus",http://dx.doi.org/10.1155/2013/595768,PMC3872095,24382964,CC BY,"Human respiratory syncytial virus (RSV) is a common cause of respiratory infection in infants and the elderly, leading to significant morbidity and mortality. The interdisciplinary fields, especially biotechnology and nanotechnology, have facilitated the development of modern detection systems for RSV. Many anti-RSV compounds like fusion inhibitors and RNAi molecules have been successful in laboratory and clinical trials. But, currently, there are no effective drugs for RSV infection even after decades of research. Effective diagnosis can result in effective treatment, but the progress in both of these facets must be concurrent. The development in prevention and treatment measures for RSV is at appreciable pace, but the implementation into clinical practice still seems a challenge. This review attempts to present the promising diverse research approaches and advancements in the area of diagnosis, prevention, and treatment that contribute to RSV management.",2013 Dec 9,"['Bawage, Swapnil Subhash', 'Tiwari, Pooja Munnilal', 'Pillai, Shreekumar', 'Dennis, Vida', 'Singh, Shree Ram']",Adv Virol,,,True
575aa2758f4a3c952d7cd9ab031eb42b25a87a96,PMC,Sensing Microbial RNA in the Cytosol,http://dx.doi.org/10.3389/fimmu.2013.00468,PMC3872322,24400006,CC BY,"The innate immune system faces the difficult task of keeping a fine balance between sensitive detection of microbial presence and avoidance of autoimmunity. To this aim, key mechanisms of innate responses rely on isolation of pathogens in specialized subcellular compartments, or sensing of specific microbial patterns absent from the host. Efficient detection of foreign RNA in the cytosol requires an additional layer of complexity from the immune system. In this particular case, innate sensors should be able to distinguish self and non-self molecules that share several similar properties. In this review, we discuss this interplay between cytosolic pattern recognition receptors and the microbial RNA they detect. We describe how microbial RNAs gain access to the cytosol, which receptors they activate and counter-strategies developed by microorganisms to avoid this response.",2013 Dec 25,"['Vabret, Nicolas', 'Blander, J. Magarian']",Front Immunol,,,True
f8f49888663fdad58dabb5d7f9f8556b36d34587,PMC,"Estimating the Diversity, Completeness, and Cross-Reactivity of the T Cell Repertoire",http://dx.doi.org/10.3389/fimmu.2013.00485,PMC3872652,24421780,CC BY,"In order to recognize and combat a diverse array of pathogens the immune system has a large repertoire of T cells having unique T cell receptors (TCRs) with only a few clones specific for any given antigen. We discuss how the number of different possible TCRs encoded in the genome (the potential repertoire) and the number of different TCRs present in an individual (the realized repertoire) can be measured. One puzzle is that the potential repertoire greatly exceeds the realized diversity of naïve T cells within any individual. We show that the existing hypotheses fail to explain why the immune system has the potential to generate far more diversity than is used in an individual, and propose an alternative hypothesis of “evolutionary sloppiness.” Another immunological puzzle is why mice and humans have similar repertoires even though humans have over 1000-fold more T cells. We discuss how the idea of the “protecton,” the smallest unit of protection, might explain this discrepancy and estimate the size of “protecton” based on available precursor frequencies data. We then consider T cell cross-reactivity – the ability of a T cell clone to respond to more than one epitope. We extend existing calculations to estimate the extent of expected cross-reactivity between the responses to different pathogens. Our results are consistent with two observations: a low probability of observing cross-reactivity between the immune responses to two randomly chosen pathogens; and the ensemble of memory cells being sufficiently diverse to generate cross-reactive responses to new pathogens.",2013 Dec 26,"['Zarnitsyna, Veronika I.', 'Evavold, Brian D.', 'Schoettle, Louis N.', 'Blattman, Joseph N.', 'Antia, Rustom']",Front Immunol,,,True
f7740a58d95fb643e40af517b3da5a3d925edb50,PMC,Aptamer-Based Therapeutics: New Approaches to Combat Human Viral Diseases,http://dx.doi.org/10.3390/ph6121507,PMC3873675,24287493,CC BY,"Viruses replicate inside the cells of an organism and continuously evolve to contend with an ever-changing environment. Many life-threatening diseases, such as AIDS, SARS, hepatitis and some cancers, are caused by viruses. Because viruses have small genome sizes and high mutability, there is currently a lack of and an urgent need for effective treatment for many viral pathogens. One approach that has recently received much attention is aptamer-based therapeutics. Aptamer technology has high target specificity and versatility, i.e., any viral proteins could potentially be targeted. Consequently, new aptamer-based therapeutics have the potential to lead a revolution in the development of anti-infective drugs. Additionally, aptamers can potentially bind any targets and any pathogen that is theoretically amenable to rapid targeting, making aptamers invaluable tools for treating a wide range of diseases. This review will provide a broad, comprehensive overview of viral therapies that use aptamers. The aptamer selection process will be described, followed by an explanation of the potential for treating virus infection by aptamers. Recent progress and prospective use of aptamers against a large variety of human viruses, such as HIV-1, HCV, HBV, SCoV, Rabies virus, HPV, HSV and influenza virus, with particular focus on clinical development of aptamers will also be described. Finally, we will discuss the challenges of advancing antiviral aptamer therapeutics and prospects for future success.",2013 Nov 25,"['Shum, Ka-To', 'Zhou, Jiehua', 'Rossi, John J.']",Pharmaceuticals (Basel),,,True
25affabb80bcf3e1a60c00fc09fd5d2e8f89ec48,PMC,Do Intensive Care Data on Respiratory Infections Reflect Influenza Epidemics?,http://dx.doi.org/10.1371/journal.pone.0083854,PMC3877112,24391837,CC BY,"OBJECTIVES: Severe influenza can lead to Intensive Care Unit (ICU) admission. We explored whether ICU data reflect influenza like illness (ILI) activity in the general population, and whether ICU respiratory infections can predict influenza epidemics. METHODS: We calculated the time lag and correlation between ILI incidence (from ILI sentinel surveillance, based on general practitioners (GP) consultations) and percentages of ICU admissions with a respiratory infection (from the Dutch National Intensive Care Registry) over the years 2003–2011. In addition, ICU data of the first three years was used to build three regression models to predict the start and end of influenza epidemics in the years thereafter, one to three weeks ahead. The predicted start and end of influenza epidemics were compared with observed start and end of such epidemics according to the incidence of ILI. RESULTS: Peaks in respiratory ICU admissions lasted longer than peaks in ILI incidence rates. Increases in ICU admissions occurred on average two days earlier compared to ILI. Predicting influenza epidemics one, two, or three weeks ahead yielded positive predictive values ranging from 0.52 to 0.78, and sensitivities from 0.34 to 0.51. CONCLUSIONS: ICU data was associated with ILI activity, with increases in ICU data often occurring earlier and for a longer time period. However, in the Netherlands, predicting influenza epidemics in the general population using ICU data was imprecise, with low positive predictive values and sensitivities.",2013 Dec 31,"['Koetsier, Antonie', 'van Asten, Liselotte', 'Dijkstra, Frederika', 'van der Hoek, Wim', 'Snijders, Bianca E.', 'van den Wijngaard, Cees C.', 'Boshuizen, Hendriek C.', 'Donker, Gé A.', 'de Lange, Dylan W.', 'de Keizer, Nicolette F.', 'Peek, Niels']",PLoS One,,,True
a0916fa29144e650632aba916141809195ab6809,PMC,An IDEA for Short Term Outbreak Projection: Nearcasting Using the Basic Reproduction Number,http://dx.doi.org/10.1371/journal.pone.0083622,PMC3877403,24391797,CC BY,"BACKGROUND: Communicable disease outbreaks of novel or existing pathogens threaten human health around the globe. It would be desirable to rapidly characterize such outbreaks and develop accurate projections of their duration and cumulative size even when limited preliminary data are available. Here we develop a mathematical model to aid public health authorities in tracking the expansion and contraction of outbreaks with explicit representation of factors (other than population immunity) that may slow epidemic growth. METHODOLOGY: The Incidence Decay and Exponential Adjustment (IDEA) model is a parsimonious function that uses the basic reproduction number R(0), along with a discounting factor to project the growth of outbreaks using only basic epidemiological information (e.g., daily incidence counts). PRINCIPAL FINDINGS: Compared to simulated data, IDEA provides highly accurate estimates of total size and duration for a given outbreak when R(0) is low or moderate, and also identifies turning points or new waves. When tested with an outbreak of pandemic influenza A (H1N1), the model generates estimated incidence at the i+1(th) serial interval using data from the i(th) serial interval within an average of 20% of actual incidence. CONCLUSIONS AND SIGNIFICANCE: This model for communicable disease outbreaks provides rapid assessments of outbreak growth and public health interventions. Further evaluation in the context of real-world outbreaks will establish the utility of IDEA as a tool for front-line epidemiologists.",2013 Dec 31,"['Fisman, David N.', 'Hauck, Tanya S.', 'Tuite, Ashleigh R.', 'Greer, Amy L.']",PLoS One,,,True
7b6a0cdab144889035b432119a497eb9cad5b9cd,PMC,"Information needs and seeking behaviour among health professionals working at public hospital and health centres in Bahir Dar, Ethiopia",http://dx.doi.org/10.1186/1472-6963-13-534,PMC3877973,24373296,CC BY,"BACKGROUND: Universal access to information for health professionals is a need to achieve “health for all strategy.” A large proportion of the population including health professionals have limited access to health information in resource limited countries. The aim of this study is to assess information needs among Ethiopian health professionals. METHODS: A cross sectional quantitative study design complemented with qualitative method was conducted among 350 health care workers in Feburary26-June5/2012. Pretested self-administered questionnaire and observation checklist were used to collect data on different variables. Data entry and data analysis were done using Epi-Info version 3.5.1 and by SPSS version19, respectively. Descriptive statistics and multivariate regression analyses were applied to describe study objectives and identify the determinants of information seeking behaviours respectively. Odds ratio with 95% CI was used to assess the association between a factor and an outcome variable. RESULTS: The majority of the respondents acknowledged the need of health information to their routine activities. About 54.0% of respondents lacked access to health information. Only 42.8% of respondents have access to internet sources. Important barriers to access information were geographical, organizational, personal, economic, educational status and time. About 58.0% of the respondents accessed information by referring their hard copies and asking senior staff. Age, sex, income, computer literacy and access, patient size, work experience and working site were significantly associated with information needs and seeking behaviour. CONCLUSIONS: The health information seeking behaviour of health professional was significant. The heaklth facilities had neither informationcenter such as library, nor internet facilities. Conducting training on managing health information, accessing computer and improving infrastructures are important interventions to facilitate evidence based descions.",2013 Dec 27,"['Andualem, Mulusew', 'Kebede, Gashaw', 'Kumie, Abera']",BMC Health Serv Res,,,True
97c615d915000b15e55f71d20e045bf939c6bca5,PMC,In-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respiratory Syndrome (MERS) Coronavirus infection,http://dx.doi.org/10.1186/1743-422X-10-359,PMC3878046,24364985,CC BY,"BACKGROUND: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes symptoms similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), yet involving an additional component of acute renal failure (ARF) according to several published case reports. Impairment of the kidney is not typically seen in Coronavirus infections. The role of kidney infection in MERS is not understood. FINDINGS: A systematic review of communicated and peer-reviewed case reports revealed differences in descriptions of kidney involvement in MERS versus SARS patients. In particular, ARF in MERS patients occurred considerably earlier after a median time to onset of 11 days (SD ±2,0 days) as opposed to 20 days for SARS, according to the literature. In-situ histological staining of the respective cellular receptors for MERS- and SARS-Coronavirus showed highly similar staining patterns with a focus of a receptor-specific signal in kidney epithelial cells. Comparative infection experiments with SARS- and MERS-CoV in primary human kidney cells versus primary human bronchial epithelial cells showed cytopathogenic infection only in kidney cells, and only if infected with MERS-CoV. Kidney epithelial cells produced almost 1000-fold more infectious MERS-CoV progeny than bronchial epithelial cells, while only a small difference was seen between cell types when infected with SARS-CoV. CONCLUSION: Epidemiological studies should analyze kidney impairment and its characteristics in MERS-CoV. Virus replication in the kidney with potential shedding in urine might constitute a way of transmission, and could explain untraceable transmission chains leading to new cases. Individual patients might benefit from early induction of renoprotective treatment.",2013 Dec 23,"['Eckerle, Isabella', 'Müller, Marcel A', 'Kallies, Stephan', 'Gotthardt, Daniel N', 'Drosten, Christian']",Virol J,,,True
d215fd9c30298cb374b6c9cbec60269c91255fcf,PMC,Chinese social media reaction to the MERS-CoV and avian influenza A(H7N9) outbreaks,http://dx.doi.org/10.1186/2049-9957-2-31,PMC3878123,24359669,CC BY,"BACKGROUND: As internet and social media use have skyrocketed, epidemiologists have begun to use online data such as Google query data and Twitter trends to track the activity levels of influenza and other infectious diseases. In China, Weibo is an extremely popular microblogging site that is equivalent to Twitter. Capitalizing on the wealth of public opinion data contained in posts on Weibo, this study used Weibo as a measure of the Chinese people’s reactions to two different outbreaks: the 2012 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak, and the 2013 outbreak of human infection of avian influenza A(H7N9) in China. METHODS: Keyword searches were performed in Weibo data collected by The University of Hong Kong’s Weiboscope project. Baseline values were determined for each keyword and reaction values per million posts in the days after outbreak information was released to the public. RESULTS: The results show that the Chinese people reacted significantly to both outbreaks online, where their social media reaction was two orders of magnitude stronger to the H7N9 influenza outbreak that happened in China than the MERS-CoV outbreak that was far away from China. CONCLUSIONS: These results demonstrate that social media could be a useful measure of public awareness and reaction to disease outbreak information released by health authorities.",2013 Dec 20,"['Fung, Isaac Chun-Hai', 'Fu, King-Wa', 'Ying, Yuchen', 'Schaible, Braydon', 'Hao, Yi', 'Chan, Chung-Hong', 'Tse, Zion Tsz-Ho']",Infect Dis Poverty,,,True
d2e396c2837b42c757e8b87e9c54a9e780324e97,PMC,Chinese social media reaction to the MERS-CoV and avian influenza A(H7N9) outbreaks,http://dx.doi.org/10.1186/2049-9957-2-31,PMC3878123,24359669,CC BY,"BACKGROUND: As internet and social media use have skyrocketed, epidemiologists have begun to use online data such as Google query data and Twitter trends to track the activity levels of influenza and other infectious diseases. In China, Weibo is an extremely popular microblogging site that is equivalent to Twitter. Capitalizing on the wealth of public opinion data contained in posts on Weibo, this study used Weibo as a measure of the Chinese people’s reactions to two different outbreaks: the 2012 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak, and the 2013 outbreak of human infection of avian influenza A(H7N9) in China. METHODS: Keyword searches were performed in Weibo data collected by The University of Hong Kong’s Weiboscope project. Baseline values were determined for each keyword and reaction values per million posts in the days after outbreak information was released to the public. RESULTS: The results show that the Chinese people reacted significantly to both outbreaks online, where their social media reaction was two orders of magnitude stronger to the H7N9 influenza outbreak that happened in China than the MERS-CoV outbreak that was far away from China. CONCLUSIONS: These results demonstrate that social media could be a useful measure of public awareness and reaction to disease outbreak information released by health authorities.",2013 Dec 20,"['Fung, Isaac Chun-Hai', 'Fu, King-Wa', 'Ying, Yuchen', 'Schaible, Braydon', 'Hao, Yi', 'Chan, Chung-Hong', 'Tse, Zion Tsz-Ho']",Infect Dis Poverty,,,False
4c7cbcc5bec46c8c956a8f05adab670eb353cc30,PMC,Chinese social media reaction to the MERS-CoV and avian influenza A(H7N9) outbreaks,http://dx.doi.org/10.1186/2049-9957-2-31,PMC3878123,24359669,CC BY,"BACKGROUND: As internet and social media use have skyrocketed, epidemiologists have begun to use online data such as Google query data and Twitter trends to track the activity levels of influenza and other infectious diseases. In China, Weibo is an extremely popular microblogging site that is equivalent to Twitter. Capitalizing on the wealth of public opinion data contained in posts on Weibo, this study used Weibo as a measure of the Chinese people’s reactions to two different outbreaks: the 2012 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak, and the 2013 outbreak of human infection of avian influenza A(H7N9) in China. METHODS: Keyword searches were performed in Weibo data collected by The University of Hong Kong’s Weiboscope project. Baseline values were determined for each keyword and reaction values per million posts in the days after outbreak information was released to the public. RESULTS: The results show that the Chinese people reacted significantly to both outbreaks online, where their social media reaction was two orders of magnitude stronger to the H7N9 influenza outbreak that happened in China than the MERS-CoV outbreak that was far away from China. CONCLUSIONS: These results demonstrate that social media could be a useful measure of public awareness and reaction to disease outbreak information released by health authorities.",2013 Dec 20,"['Fung, Isaac Chun-Hai', 'Fu, King-Wa', 'Ying, Yuchen', 'Schaible, Braydon', 'Hao, Yi', 'Chan, Chung-Hong', 'Tse, Zion Tsz-Ho']",Infect Dis Poverty,,,True
33019198857c41e85955b2b731077ab3ea57c85b,PMC,Lineage specific antigenic differences in porcine torovirus hemagglutinin-esterase (PToV-HE) protein,http://dx.doi.org/10.1186/1297-9716-44-126,PMC3878402,24364900,CC BY,"Hemagglutinin-esterases (HE) are viral envelope proteins present in some members from the toro-, corona- and orthomyxovirus families, all related with enteric and/or respiratory tract infections. HE proteins mediate reversible binding to sialic acid receptor determinants, very abundant glycan residues in the enteric and respiratory tracts. The role of the HE protein during the torovirus infection cycle remains unknown, although it is believed to be important in the natural infection process. The phylogenetic analysis of HE coding sequences from porcine torovirus (PToV) field strains revealed the existence of two distinct HE lineages. In a previous study, PToV virus strains with HE proteins from the two lineages were found coexisting in a pig herd, and they were even obtained from the same animal at two consecutive sampling time points. In this work, we report antigenic differences between the two HE lineages, and discuss the possible implications that the coexistence of viruses belonging to both lineages might have on the spread and sustainment of PToV infection in the farms.",2013 Dec 23,"['Pignatelli, Jaime', 'Alonso-Padilla, Julio', 'Rodríguez, Dolores']",Vet Res,,,True
753b8924471c5747cc1600e92a4cfae5d3584439,PMC,Lineage specific antigenic differences in porcine torovirus hemagglutinin-esterase (PToV-HE) protein,http://dx.doi.org/10.1186/1297-9716-44-126,PMC3878402,24364900,CC BY,"Hemagglutinin-esterases (HE) are viral envelope proteins present in some members from the toro-, corona- and orthomyxovirus families, all related with enteric and/or respiratory tract infections. HE proteins mediate reversible binding to sialic acid receptor determinants, very abundant glycan residues in the enteric and respiratory tracts. The role of the HE protein during the torovirus infection cycle remains unknown, although it is believed to be important in the natural infection process. The phylogenetic analysis of HE coding sequences from porcine torovirus (PToV) field strains revealed the existence of two distinct HE lineages. In a previous study, PToV virus strains with HE proteins from the two lineages were found coexisting in a pig herd, and they were even obtained from the same animal at two consecutive sampling time points. In this work, we report antigenic differences between the two HE lineages, and discuss the possible implications that the coexistence of viruses belonging to both lineages might have on the spread and sustainment of PToV infection in the farms.",2013 Dec 23,"['Pignatelli, Jaime', 'Alonso-Padilla, Julio', 'Rodríguez, Dolores']",Vet Res,,,False
d23a5e1b6a5c6036c3e45e7c6d9019a59ddfd6bd,PMC,Minimizing the threat of pandemic emergence from avian influenza in poultry systems,http://dx.doi.org/10.1186/1471-2334-13-592,PMC3878446,24341669,CC BY,"BACKGROUND: Live-animal markets are a culturally important feature of meat distribution chains in many populations, yet they provide an opportunity for the maintenance and transmission of potentially emergent zoonotic pathogens. The ongoing human outbreak of avian H7N9 in China highlights the need for increased surveillance and control in these live-bird markets (LBMs). DISCUSSION: Closure of retail markets in affected areas rapidly decreased human cases to rare, sporadic occurrence, but little attention has been paid thus far to the role of upstream elements of the poultry distribution chain such as wholesale markets. This could partly explain why transmission in poultry populations has not been eliminated more broadly. We present surveillance data from both wholesale live-bird markets (wLBMs) and rLBMs in Shantou, China (from 2004–2006), and call on disease-dynamic theory to illustrate why closing rLBMs has only minor effects on the overall volume of transmission. We show that the length of time birds stay in rLBMs can severely limit transmission there, but that the system-wide effect may be reduced substantially by high levels of transmission upstream of retail markets. SUMMARY: Management plans that minimize transmission throughout the entire poultry supply chain are essential for minimizing exposure to the public. These include reducing stay-time of birds in markets to 1 day, standardizing poultry supply chains to limit transmission in pre-retail settings, and monitoring strains with epidemiological traits that pose a high risk of emergence. These actions will further limit human exposure to extant viruses and reduce the likelihood of the emergence of novel strains by decreasing the overall volume of transmission.",2013 Dec 16,"['Pepin, Kim M', 'Lloyd-Smith, James O', 'Webb, Colleen T', 'Holcomb, Karen', 'Zhu, Huachen', 'Guan, Yi', 'Riley, Steven']",BMC Infect Dis,,,True
8df741c3cb3a548994916cbc0db540c43f374bc7,PMC,Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation,http://dx.doi.org/10.1186/1756-8722-6-94,PMC3878524,24341630,CC BY,"Viral infections are important causes of morbidity and mortality after allogeneic stem cell hematopoietic transplantation (allo-HSCT). Although most viral infections present with asymptomatic or subclinical manifestations, viruses may result in fatal complications in severe immunocompromised recipients. Reactivation of latent viruses, such as herpesviruses, is frequent during the immunosuppression that occurs with allo-HSCT. Viruses acquired from community, such as the respiratory and gastrointestinal viruses, are also important pathogens of post-transplant viral diseases. Currently, molecular diagnostic methods have replaced or supplemented traditional methods, such as viral culture and antigen detection, in diagnosis of viral infections. The utilization of polymerase chain reaction facilitates the early diagnosis. In view of lacking efficacious agents for treatment of viral diseases, prevention of viral infections is extremely valuable. Application of prophylactic strategies including preemptive therapy reduces viral infections and diseases. Adoptive cellular therapy for restoring virus-specific immunity is a promising method in the treatment of viral diseases.",2013 Dec 17,"['Lin, Ren', 'Liu, Qifa']",J Hematol Oncol,,,True
5977507d38a03786e12e8e48cda0b431871af042,PMC,Single injection recombinant vesicular stomatitis virus vaccines protect ferrets against lethal Nipah virus disease,http://dx.doi.org/10.1186/1743-422X-10-353,PMC3878732,24330654,CC BY,"BACKGROUND: Nipah virus (NiV) is a highly pathogenic zoonotic agent in the family Paramyxoviridae that is maintained in nature by bats. Outbreaks have occurred in Malaysia, Singapore, India, and Bangladesh and have been associated with 40 to 75% case fatality rates. There are currently no vaccines or postexposure treatments licensed for combating human NiV infection. METHODS AND RESULTS: Four groups of ferrets received a single vaccination with different recombinant vesicular stomatitis virus vectors expressing: Group 1, control with no glycoprotein; Group 2, the NiV fusion protein (F); Group 3, the NiV attachment protein (G); and Group 4, a combination of the NiV F and G proteins. Animals were challenged intranasally with NiV 28 days after vaccination. Control ferrets in Group 1 showed characteristic clinical signs of NiV disease including respiratory distress, neurological disorders, viral load in blood and tissues, and gross lesions and antigen in target tissues; all animals in this group succumbed to infection by day 8. Importantly, all specifically vaccinated ferrets in Groups 2-4 showed no evidence of clinical illness and survived challenged. All animals in these groups developed anti-NiV F and/or G IgG and neutralizing antibody titers. While NiV RNA was detected in blood at day 6 post challenge in animals from Groups 2-4, the levels were orders of magnitude lower than animals from control Group 1. CONCLUSIONS: These data show protective efficacy against NiV in a relevant model of human infection. Further development of this technology has the potential to yield effective single injection vaccines for NiV infection.",2013 Dec 13,"['Mire, Chad E', 'Versteeg, Krista M', 'Cross, Robert W', 'Agans, Krystle N', 'Fenton, Karla A', 'Whitt, Michael A', 'Geisbert, Thomas W']",Virol J,,,True
39b4ca41bed615d00441db0664ce67e473e74ba5,PMC,VIRsiRNApred: a web server for predicting inhibition efficacy of siRNAs targeting human viruses,http://dx.doi.org/10.1186/1479-5876-11-305,PMC3878835,24330765,CC BY,"BACKGROUND: Selection of effective viral siRNA is an indispensable step in the development of siRNA based antiviral therapeutics. Despite immense potential, a viral siRNA efficacy prediction algorithm is still not available. Moreover, performances of the existing general mammalian siRNA efficacy predictors are not satisfactory for viral siRNAs. Therefore, we have developed “VIRsiRNApred” a support vector machine (SVM) based method for predicting the efficacy of viral siRNA. METHODS: In the present study, we have employed a new dataset of 1725 viral siRNAs with experimentally verified quantitative efficacies tested under heterogeneous experimental conditions and targeting as many as 37 important human viruses including HIV, Influenza, HCV, HBV, SARS etc. These siRNAs were divided into training (T(1380)) and validation (V(345)) datasets. Important siRNA sequence features including mono to penta nucleotide frequencies, binary pattern, thermodynamic properties and secondary structure were employed for model development. RESULTS: During 10-fold cross validation on T(1380) using hybrid approach, we achieved a maximum Pearson Correlation Coefficient (PCC) of 0.55 between predicted and actual efficacy of viral siRNAs. On V(345) independent dataset, our best model achieved a maximum correlation of 0.50 while existing general siRNA prediction methods showed PCC from 0.05 to 0.18. However, using leave one out cross validation PCC was improved to 0.58 and 0.55 on training and validation datasets respectively. SVM performed better than other machine learning techniques used like ANN, KNN and REP Tree. CONCLUSION: VIRsiRNApred is the first algorithm for predicting inhibition efficacy of viral siRNAs which is developed using experimentally verified viral siRNAs. We hope this algorithm would be useful in predicting highly potent viral siRNA to aid siRNA based antiviral therapeutics development. The web server is freely available at http://crdd.osdd.net/servers/virsirnapred/.",2013 Dec 11,"['Qureshi, Abid', 'Thakur, Nishant', 'Kumar, Manoj']",J Transl Med,,,True
15d52271667c76c6db91907ad72ecb65fb88ec84,PMC,Phylogeography of influenza A H5N1 clade 2.2.1.1 in Egypt,http://dx.doi.org/10.1186/1471-2164-14-871,PMC3878885,24325606,CC BY,"BACKGROUND: Influenza A H5N1 has killed millions of birds and raises serious public health concern because of its potential to spread to humans and cause a global pandemic. While the early focus was in Asia, recent evidence suggests that Egypt is a new epicenter for the disease. This includes characterization of a variant clade 2.2.1.1, which has been found almost exclusively in Egypt. We analyzed 226 HA and 92 NA sequences with an emphasis on the H5N1 2.2.1.1 strains in Egypt using a Bayesian discrete phylogeography approach. This allowed modeling of virus dispersion between Egyptian governorates including the most likely origin. RESULTS: Phylogeography models of hemagglutinin (HA) and neuraminidase (NA) suggest Ash Sharqiyah as the origin of virus spread, however the support is weak based on Kullback–Leibler values of 0.09 for HA and 0.01 for NA. Association Index (AI) values and Parsimony Scores (PS) were significant (p-value < 0.05), indicating that dispersion of H5N1 in Egypt was geographically structured. In addition, the Ash Sharqiyah to Al Gharbiyah and Al Fayyum to Al Qalyubiyah routes had the strongest statistical support. CONCLUSION: We found that the majority of routes with strong statistical support were in the heavily populated Delta region. In particular, the Al Qalyubiyah governorate appears to represent a popular location for virus transition as it represented a large portion of branches in both trees. However, there remains uncertainty about virus dispersion to and from this location and thus more research needs to be conducted in order to examine this. Phylogeography can highlight the drivers of H5N1 emergence and spread. This knowledge can be used to target public health efforts to reduce morbidity and mortality. For Egypt, future work should focus on using data about vaccination and live bird markets in phylogeography models to study their impact on H5N1 diffusion within the country.",2013 Dec 10,"['Scotch, Matthew', 'Mei, Changjiang', 'Makonnen, Yilma J', 'Pinto, Julio', 'Ali, AbdelHakim', 'Vegso, Sally', 'Kane, Michael', 'Sarkar, Indra Neil', 'Rabinowitz, Peter']",BMC Genomics,,,True
d2f29c0bf8f5b9bf9d357001a62b42244698b298,PMC,The Gene Expression Profile of Peripheral Blood Mononuclear Cells from EV71-Infected Rhesus Infants and the Significance in Viral Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0083766,PMC3879270,24392094,CC BY,"Enterovirus 71 (EV71) is the major pathogen responsible for fatal hand, foot and mouth disease (HFMD). Our previous work reported on an EV71-infected rhesus monkey infant model that presented with histo-pathologic changes of the central nervous system (CNS) and lungs. This study is focused on the correlated modulation of gene expression in the peripheral blood mononuclear cells (PBMCs) from EV71-infected rhesus monkey infants. The expression of more than 500 functional genes associated with multiple pathways was modulated. The expression of genes associated with immune inflammatory responses was up-regulated during the period from days 4 to 10 post-infection. The expression of two genes (TAC1 and IL17A), which play major roles in inflammatory reactions, was remarkably up-regulated during the infection period. Furthermore, a higher expression level of the TAC1 gene was identified in the CNS compared to the lungs, but a high expression level of the IL-17A gene was observed in the lungs and not in the CNS. The results of this study suggest at least two facts about EV71 infection, which are that: the TAC1 gene that encodes substance P and neurokinin-A is present in both PBMCs and the hypothalamus; and the up-regulation of IL-17A is sustained in the peripheral blood.",2014 Jan 2,"['Zhang, Ying', 'Yang, Erxia', 'Pu, Jing', 'Liu, Longding', 'Che, Yanchun', 'Wang, Jingjing', 'Liao, Yun', 'Wang, Lichun', 'Ding, Dong', 'Zhao, Ting', 'Ma, Na', 'Song, Ming', 'Wang, Xi', 'Shen, Dong', 'Tang, Donghong', 'Huang, Hongtai', 'Zhang, Zhixiao', 'Chen, Dai', 'Feng, Mingfei', 'Li, Qihan']",PLoS One,,,True
8fa2be5d5abb0473dda3892cf6f42a318f87b39b,PMC,Transcriptome Analysis of Houttuynia cordata Thunb. by Illumina Paired-End RNA Sequencing and SSR Marker Discovery,http://dx.doi.org/10.1371/journal.pone.0084105,PMC3879290,24392108,CC BY,"BACKGROUND: Houttuynia cordata Thunb. is an important traditional medical herb in China and other Asian countries, with high medicinal and economic value. However, a lack of available genomic information has become a limitation for research on this species. Thus, we carried out high-throughput transcriptomic sequencing of H. cordata to generate an enormous transcriptome sequence dataset for gene discovery and molecular marker development. PRINCIPAL FINDINGS: Illumina paired-end sequencing technology produced over 56 million sequencing reads from H. cordata mRNA. Subsequent de novo assembly yielded 63,954 unigenes, 39,982 (62.52%) and 26,122 (40.84%) of which had significant similarity to proteins in the NCBI nonredundant protein and Swiss-Prot databases (E-value <10(−5)), respectively. Of these annotated unigenes, 30,131 and 15,363 unigenes were assigned to gene ontology categories and clusters of orthologous groups, respectively. In addition, 24,434 (38.21%) unigenes were mapped onto 128 pathways using the KEGG pathway database and 17,964 (44.93%) unigenes showed homology to Vitis vinifera (Vitaceae) genes in BLASTx analysis. Furthermore, 4,800 cDNA SSRs were identified as potential molecular markers. Fifty primer pairs were randomly selected to detect polymorphism among 30 samples of H. cordata; 43 (86%) produced fragments of expected size, suggesting that the unigenes were suitable for specific primer design and of high quality, and the SSR marker could be widely used in marker-assisted selection and molecular breeding of H. cordata in the future. CONCLUSIONS: This is the first application of Illumina paired-end sequencing technology to investigate the whole transcriptome of H. cordata and to assemble RNA-seq reads without a reference genome. These data should help researchers investigating the evolution and biological processes of this species. The SSR markers developed can be used for construction of high-resolution genetic linkage maps and for gene-based association analyses in H. cordata. This work will enable future functional genomic research and research into the distinctive active constituents of this genus.",2014 Jan 2,"['Wei, Lin', 'Li, Shenghua', 'Liu, Shenggui', 'He, Anna', 'Wang, Dan', 'Wang, Jie', 'Tang, Yulian', 'Wu, Xianjin']",PLoS One,,,True
293854bf36effa5c8080201deaa19b213d4465c9,PMC,Effect of facemasks on empathy and relational continuity: a randomised controlled trial in primary care,http://dx.doi.org/10.1186/1471-2296-14-200,PMC3879648,24364989,CC BY,"BACKGROUND: There is limited evidence to support the use of facemasks in preventing infection for primary care professionals. Negative effects on communication has been suggested when the physician wears a facemask. As communication skills and doctor patient relationship are essential to primary care consultations, the effects of doctor’s facemask wearing were explored. METHOD: A randomised controlled study was conducted in primary care to explore the effects of doctors wearing facemasks on patients’ perception of doctors’ empathy, patient enablement and patient satisfaction. Primary care doctors were randomized to mask wearing and non mask wearing clinical consultations in public primary care clinics in Hong Kong. Patients’ views were gathered using the Consultation and Relational Empathy (CARE) Measure, Patient Enablement Instrument (PEI) and an overall satisfaction rating scale. The effects of face mask wearing were investigated using multilevel (hierarchical) modelling. RESULTS: 1,030 patients were randomised to doctor-mask wearing consultations (n = 514) and non mask wearing consultations (n = 516). A significant and negative effect was found in the patients’ perception of the doctors’ empathy (CARE score reduction -0.98, p-value = 0.04). In the more established doctor-patient relationship, the effect of doctors’ mask wearing was more pronounced (CARE score reduction -5.67, p-value = 0.03). CONCLUSION: This study demonstrates that when doctors wearing a facemask during consultations, this has a significant negative impact on the patient’s perceived empathy and diminish the positive effects of relational continuity. Consideration should be taken in planning appropriate use of facemasks in infectious disease policy for primary care and other healthcare professionals at a national, local or practice level. CLINICAL TRIAL REGISTRATION: This trial was registered on Chinese Clinical Trial Register (ChiCTR). Registration no.: ChiCTR-TTRCC-12002519. URL: http://www.chictr.org/en/proj/show.aspx?proj=3486. Due to administrative error, registration of trial did not take place until after the trial started on 1(st) August 2011 and registration number was released on 21(st) September 2012.",2013 Dec 24,"['Wong, Carmen Ka Man', 'Yip, Benjamin Hon Kei', 'Mercer, Stewart', 'Griffiths, Sian', 'Kung, Kenny', 'Wong, Martin Chi-sang', 'Chor, Josette', 'Wong, Samuel Yeung-shan']",BMC Fam Pract,,,True
c1e4465687748c1d03b1c648b1558d1051859b5a,PMC,A cross-sectional study of the clinical characteristics of hospitalized children with community-acquired pneumonia in eight eastern cities in China,http://dx.doi.org/10.1186/1472-6882-13-367,PMC3880031,24364897,CC BY,"BACKGROUND: Community-acquired pneumonia in children is common in China. To understand current clinical characteristics and practice, we conducted a cross-sectional study to analyze quality of care on childhood pneumonia in eight eastern cities in China. METHODS: Consecutive hospital records between January 1, 2010 and December 31, 2010 were collected from 13 traditional Chinese medicine (TCM) and western medicine (WM) hospitals in February, May, August, and November (25 cases per season, 100 cases over the year), respectively. A predesigned case report form was used to extract data from the hospital medical records. RESULTS: A total of 1298 cases were collected and analyzed. Symptoms and signs upon admission at TCM and WM hospitals were cough (99.3% vs. 98.6%), rales (84.8% vs. 75.0%), phlegm (83.3% vs. 49.1%), and fever (74.9% vs. 84.0%) in frequency. Patients admitted to WM hospitals had symptoms and signs for a longer period prior to admission than patients admitted to TCM hospitals. Testing to identify etiologic agents was performed in 1140 cases (88.4%). Intravenous antibiotics were administered in 99.3% (595/598) of cases in TCM hospitals and in 98.6% (699/700) of cases in WM hospitals. Besides, Chinese herbal extract injection was used more frequently in TCM hospitals (491 cases, 82.1%) than in WM hospitals (212 cases, 30.3%) (p < 0.01). At discharge, 818 cases (63.0%) were clinically cured, with a significant difference between the cure rates in TCM (87.6%) and WM hospitals (42.0%) (OR = 9.8, 95% confidence interval (CI): 7.3 ~ 12.9, p < 0.01). Pathogen and previous medical history were more likely associated with the disappearance of rales (OR = 7.2, 95% CI: 4.8 ~ 10.9). Adverse effects were not reported from the medical records. CONCLUSIONS: Intravenous use of antibiotics is highly prevalent in children with community-acquired pneumonia regardless of aetiology. There was difference between TCM and WM hospitals with regard to symptom profile and the use of antibiotics. Intravenous use of herbal injection was higher in TCM hospitals than in WM hospitals. Most of the cases were diagnosed based on clinical signs and symptoms without sufficient confirmation of aetiology. Audit of current practice is urgently needed to improve care.",2013 Dec 23,"['Wang, Xue-Feng', 'Liu, Jian-Ping', 'Shen, Kun-Ling', 'Ma, Rong', 'Cui, Zhen-Ze', 'Deng, Li', 'Shang, Yun-Xiao', 'Zhao, De-Yu', 'Wang, Li-Bo', 'Wan, Li-Ya', 'Sun, Yi-Qiu', 'Li, Yan-Ning', 'Jiang, Zhi-Yan', 'Xu, Hua', 'Li, Xin-Min', 'Wu, Zhen-Qi', 'Liu, Zhao-Lan', 'Hu, Ying-Hui', 'Huang, Yan', 'He, Chun-Hui', 'Zhang, Han', 'Jiang, Yong-Hong', 'Liu, Hua', 'Wang, Zi']",BMC Complement Altern Med,,,True
14a0b8d9f05d4baef14cfa9178748cb9d504d523,PMC,Design and Experimental Approach to the Construction of a Human Signal-Molecule-Profiling Database,http://dx.doi.org/10.3390/ijerph10126887,PMC3881147,24351788,CC BY,"The human signal-molecule-profiling database (HSMPD) is designed as a prospective medical database for translational bioinformatics (TBI). To explore the feasibility of low-cost database construction, we studied the roadmap of HSMPD. A HSMPD-oriented tool, called “signal-molecule-profiling (SMP) chip” was developed for data acquisition, which can be employed in the routine blood tests in hospitals; the results will be stored in the HSMPD system automatically. HSMPD system can provide data services for the TBI community, which generates a stable income to support the data acquisition. The small-scale experimental test was performed in the hospital to verify SMP chips and the demo HSMPD software. One hundred and eighty nine complete SMP records were collected, and the demo HSMPD system was also evaluated in the survey study on patients and doctors. The function of SMP chip was verified, whereas the demo HSMPD software needed to be improved. The survey study showed that patients would only accept free tests of SMP chips when they originally needed blood examinations. The study indicated that the construction of HSMPD relies on the self-motivated cooperation of the TBI community and the traditional healthcare system. The proposed roadmap potentially provides an executable solution to build the HSMPD without high costs.",2013 Dec 9,"['Zhao, Xinyan', 'Dong, Tao']",Int J Environ Res Public Health,,,True
8a5accd8df7fcfcef5fb8b467e2cc8caa7c631a4,PMC,A Neutralization Epitope in the Hepatitis C Virus E2 Glycoprotein Interacts with Host Entry Factor CD81,http://dx.doi.org/10.1371/journal.pone.0084346,PMC3882236,24400084,CC0,"The identification of a specific immunogenic candidate that will effectively activate the appropriate pathway for neutralizing antibody production is fundamental for vaccine design. By using a monoclonal antibody (1H8) that neutralizes HCV in vitro, we have demonstrated here that 1H8 recognized an epitope mapped between residues A524 and W529 of the E2 protein. We also found that the epitope residues A524, P525, Y527 and W529 were crucial for antibody binding, while the residues T526, Y527 and W529 within the same epitope engaged in the interaction with the host entry factor CD81. Furthermore, we detected “1H8-like” antibodies, defined as those with amino acid-specificity similar to 1H8, in the plasma of patients with chronic HCV infection. The time course study of plasma samples from Patient H, a well-characterized case of post-transfusion hepatitis C, showed that “1H8-like” antibodies could be detected in a sample collected almost two years after the initial infection, thus confirming the immunogenicity of this epitope in vivo. The characterization of this neutralization epitope with a function in host entry factor CD81 interaction should enhance our understanding of antibody-mediated neutralization of HCV infections.",2014 Jan 6,"['Zhao, Zhong', 'Zhong, Lilin', 'Elrod, Elizabeth', 'Struble, Evi', 'Ma, Li', 'Yan, Hailing', 'Harman, Christine', 'Deng, Lu', 'Virata-Theimer, Maria Luisa', 'Liu, Peter', 'Alter, Harvey', 'Grakoui, Arash', 'Zhang, Pei']",PLoS One,,,True
372f3a4aac120be6b70f0b3d51481ab2679a6b92,PMC,"Full-Genome Analysis of a Canine Pneumovirus Causing Acute Respiratory Disease in Dogs, Italy",http://dx.doi.org/10.1371/journal.pone.0085220,PMC3882280,24400129,CC BY,"An outbreak of canine infectious respiratory disease (CIRD) associated to canine pneumovirus (CnPnV) infection is reported. The outbreak occurred in a shelter of the Apulia region and involved 37 out of 350 dogs that displayed cough and/or nasal discharge with no evidence of fever. The full-genomic characterisation showed that the causative agent (strain Bari/100-12) was closely related to CnPnVs that have been recently isolated in the USA, as well as to murine pneumovirus, which is responsible for respiratory disease in mice. The present study represents a useful contribution to the knowledge of the pathogenic potential of CnPnV and its association with CIRD in dogs. Further studies will elucidate the pathogenicity and epidemiology of this novel pneumovirus, thus addressing the eventual need for specific vaccines.",2014 Jan 6,"['Decaro, Nicola', 'Pinto, Pierfrancesco', 'Mari, Viviana', 'Elia, Gabriella', 'Larocca, Vittorio', 'Camero, Michele', 'Terio, Valentina', 'Losurdo, Michele', 'Martella, Vito', 'Buonavoglia, Canio']",PLoS One,,,True
4e9183ccee2b50199a61683e3d261417ab182bda,PMC,Viral encephalitis caused by respiratory viruses,http://dx.doi.org/10.1186/1471-2334-13-S1-P78,PMC3882642,,CC BY,,2013 Dec 16,"['Vişan, Angelica', 'Luminos, Monica', 'Vasile, Magda', 'Drăgănescu, Anca', 'Jugulete, Gheorghiță', 'Bilaşco, Anuța', 'Negulescu, Cristina', 'Kouris, Camelia', 'Măntescu, Ruxandra', 'Merişescu, Mădălina Maria', 'Osman, Endis', 'Șchiopu, Sabina', 'Florea, Dragoş', 'Oțelea, Dan']",BMC Infect Dis,,,False
2804ea9b709694627657763fd17564d0323a5dcf,PMC,Multi-omic network signatures of disease,http://dx.doi.org/10.3389/fgene.2013.00309,PMC3882664,24432028,CC BY,"To better understand dynamic disease processes, integrated multi-omic methods are needed, yet comparing different types of omic data remains difficult. Integrative solutions benefit experimenters by eliminating potential biases that come with single omic analysis. We have developed the methods needed to explore whether a relationship exists between co-expression network models built from transcriptomic and proteomic data types, and whether this relationship can be used to improve the disease signature discovery process. A naïve, correlation based method is utilized for comparison. Using publicly available infectious disease time series data, we analyzed the related co-expression structure of the transcriptome and proteome in response to SARS-CoV infection in mice. Transcript and peptide expression data was filtered using quality scores and subset by taking the intersection on mapped Entrez IDs. Using this data set, independent co-expression networks were built. The networks were integrated by constructing a bipartite module graph based on module member overlap, module summary correlation, and correlation to phenotypes of interest. Compared to the module level results, the naïve approach is hindered by a lack of correlation across data types, less significant enrichment results, and little functional overlap across data types. Our module graph approach avoids these problems, resulting in an integrated omic signature of disease progression, which allows prioritization across data types for down-stream experiment planning. Integrated modules exhibited related functional enrichments and could suggest novel interactions in response to infection. These disease and platform-independent methods can be used to realize the full potential of multi-omic network signatures. The data (experiment SM001) are publically available through the NIAID Systems Virology (https://www.systemsvirology.org) and PNNL (http://omics.pnl.gov) web portals. Phenotype data is found in the supplementary information. The ProCoNA package is available as part of Bioconductor 2.13.",2014 Jan 7,"['Gibbs, David L.', 'Gralinski, Lisa', 'Baric, Ralph S.', 'McWeeney, Shannon K.']",Front Genet,,,True
5e8f40e1096456d1b5b0c24b57104bf15f45d37e,PMC,Two Different Conformations in Hepatitis C Virus p7 Protein Account for Proton Transport and Dye Release,http://dx.doi.org/10.1371/journal.pone.0078494,PMC3883635,24409277,CC BY,"The p7 protein from the hepatitis C virus (HCV) is a 63 amino acid long polypeptide that is essential for replication, and is involved in protein trafficking and proton transport. Therefore, p7 is a possible target for antivirals. The consensus model for the channel formed by p7 protein is a hexameric or heptameric oligomer of α-helical hairpin monomers, each having two transmembrane domains, TM1 and TM2, where the N-terminal TM1 would face the lumen of this channel. A reported high-throughput functional assay to search for p7 channel inhibitors is based on carboxyfluorescein (CF) release from liposomes after p7 addition. However, the rationale for the dual ability of p7 to serve as an ion or proton channel in the infected cell, and to permeabilize membranes to large molecules like CF is not clear. We have recreated both activities in vitro, examining the conformation present in these assays using infrared spectroscopy. Our results indicate that an α-helical form of p7, which can transport protons, is not able to elicit CF release. In contrast, membrane permeabilization to CF is observed when p7 contains a high percentage of β-structure, or when using a C-terminal fragment of p7, encompassing TM2. We propose that the reported inhibitory effect of some small compounds, e.g., rimantadine, on both CF release and proton transport can be explained via binding to the membrane-inserted C-terminal half of p7, increasing its rigidity, in a similar way to the influenza A M2-rimantadine interaction.",2014 Jan 7,"['Gan, Siok Wan', 'Surya, Wahyu', 'Vararattanavech, Ardcharaporn', 'Torres, Jaume']",PLoS One,,,True
b0e5a700bc9e8fe25e5c3f2c10976314cb30c150,PMC,Normal Thoracic Radiographic Appearance of the Cynomolgus Monkey (Macaca fascicularis),http://dx.doi.org/10.1371/journal.pone.0084599,PMC3885584,24416248,CC BY,"BACKGROUND: The cynomolgus monkey (Macaca fascicularis) has been increasingly used as a non-human primate model in biomedical research. As establishing baseline thoracic radiography for the cynomolgus monkey is essential, we tested the hypothesis that age and sex may affect the thoracic radiography parameters of this species. METHODS: Here, 697 healthy cynomolgus monkeys were segregated by sex and age (three age groups: 25–36 months, 37–48 months, 49–60 months). The lung length (LL), maximal interior thoracic depth (TD), maximal interior thoracic breadth (TBr), cardiac silhouette breadth (CBr), cardiothoracic ratio (CR), right and left costophrenic angles (RCA and LCA), and right hilar height ratio (R-HHR) were assessed by chest film. Statistical analysis was applied to examine the effect of age, sex, and age × sex interactions. RESULTS: Significant effects by age were shown for LL, TD, TBr, CBr, and CR. Significant effects by sex were found for TD, TBr, CBr, CR, and R-HHR. Significant effects by age × sex were observed for TD, TBr, CBr, and CR. Both TD and TBr increased with age in both sexes, and both were significantly higher in males than in females in the group aged 49–60 months. CBr increased with age and was significantly higher in males than in females across all age groups. CR declined with age and was significantly higher in males than females across all age groups, and CR was similar or slightly higher relative to those previously found in other non-human primate species. As to the other parameters with no significant sex nor age-related differences, the R-HHR was greater than 1.00, and the angulation of bilateral costophrenic angles were sharp. CONCLUSIONS: The thoracic radiographic parameters for the healthy cynomolgus monkey presented here should prove useful in veterinary practice, research involving non-human primate models of respiratory or cardiovascular disorders, and morphological studies on cynomolgus monkeys.",2014 Jan 8,"['Xie, Liang', 'Zhou, Qinming', 'Liu, Shigang', 'Wu, Qingyuan', 'Ji, Yongjia', 'Zhang, Lujun', 'Xu, Fan', 'Gong, Wei', 'Melgiri, Narayan D.', 'Xie, Peng']",PLoS One,,,True
5912189e6ca5053f8e7a2de341c90341f737aa7e,PMC,"Pandemic Influenza Virus 2009 H1N1 and Adenovirus in a High Risk Population of Young Adults: Epidemiology, Comparison of Clinical Presentations, and Coinfection",http://dx.doi.org/10.1371/journal.pone.0085094,PMC3885690,24416345,CC0,"BACKGROUND: In 2009, pandemic H1N1 influenza virus (2009 H1N1) emerged worldwide, causing morbidity and mortality that disproportionately affected young adults. Upper respiratory infection (URI), largely due to adenovirus, is an endemic cause of morbidity in military training. Whether clinical presentations differ or excess morbidity results from coinfection is unclear. METHODS: The Center for Advanced Molecular Detection evaluates epidemiology and rapid diagnostics of respiratory pathogens in trainees with URI. From May 1, 2009, to November 30, 2009, demographic, clinical, and PCR data from throat and nasal specimens for adenovirus and 2009 H1N1 were prospectively collected. RESULTS: 375 trainees with URI enrolled and were tested for both adenovirus and 2009 H1N1 by PCR (median age 20; 89% male). Adenovirus PCR was positive in 72% (96% serotype E-4) and 2009 H1N1 in 20%. Males were more likely to have adenovirus and females more likely to have 2009 H1N1 (p = 0.047). Subjects with 2009 H1N1 presented an average of 1 week earlier in training, had shorter illness duration before enrollment, less sore throat, diarrhea, and fewer abnormal findings on throat exam. Coryza and cough were more common with 2009 H1N1 compared to adenovirus. Subjects with 2009 H1N1 were less likely to have adenovirus than those without, despite persistently high frequencies of adenovirus detections during peak 2009 H1N1 weeks (15% vs. 83%, p < 0.01). Coinfection with adenovirus and 2009 H1N1 was rare (4%). Rates of hospitalization and pneumonia did not differ between the adenovirus, 2009 H1N1, or coinfected groups. CONCLUSION: Military trainees with 2009 H1N1 vs. adenovirus have differing clinical presentations, and males are more likely to have adenovirus. Despite high frequencies of adenovirus infection, coinfection with adenovirus and 2009 H1N1 is rare and apparently does not result in increased morbidity.",2014 Jan 8,"['Yun, Heather C.', 'Fugate, William H.', 'Murray, Clinton K.', 'Cropper, Thomas L.', 'Lott, Lisa', 'McDonald, J. Matthew']",PLoS One,,,True
239cd6dbc4b75c51256acc527ae69394b891bc1d,PMC,CD13 promotes mesenchymal stem cell-mediated regeneration of ischemic muscle,http://dx.doi.org/10.3389/fphys.2013.00402,PMC3885827,24409152,CC BY,"Mesenchymal stem cells (MSCs) are multipotent, tissue-resident cells that can facilitate tissue regeneration and thus, show great promise as potential therapeutic agents. Functional MSCs have been isolated and characterized from a wide array of adult tissues and are universally identified by the shared expression of a core panel of MSCs markers. One of these markers is the multifunctional cell surface peptidase CD13 that has been shown to be expressed on human and murine MSCs from many tissues. To investigate whether this universal expression indicates a functional role for CD13 in MSC biology we isolated, expanded and characterized MSCs from bone marrow of wild type (WT) and CD13(KO) mice. Characterization of these cells demonstrated that both WT and CD13(KO) MSCs expressed the full complement of MSC markers (CD29, CD44, CD49e, CD105, Sca1), showed comparable proliferation rates and were capable of differentiating toward the adipogenic and osteogenic lineages. However, MSCs lacking CD13 were unable to differentiate into vascular cells, consistent with our previous characterization of CD13 as an angiogenic regulator. Compared to WT MSCs, adhesion and migration on various extracellular matrices of CD13(KO) MSCs were significantly impaired, which correlated with decreased phospho-FAK levels and cytoskeletal alterations. Crosslinking human MSCs with activating CD13 antibodies increased cell adhesion to endothelial monolayers and induced FAK activation in a time dependent manner. In agreement with these in vitro data, intramuscular injection of CD13(KO) MSCs in a model of severe ischemic limb injury resulted in significantly poorer perfusion, decreased ambulation, increased necrosis and impaired vascularization compared to those receiving WT MSCs. This study suggests that CD13 regulates FAK activation to promote MSC adhesion and migration, thus, contributing to MSC-mediated tissue repair. CD13 may present a viable target to enhance the efficacy of mesenchymal stem cell therapies.",2014 Jan 9,"['Rahman, M. Mamunur', 'Subramani, Jaganathan', 'Ghosh, Mallika', 'Denninger, Jiyeon K.', 'Takeda, Kotaro', 'Fong, Guo-Hua', 'Carlson, Morgan E.', 'Shapiro, Linda H.']",Front Physiol,,,True
317f9c2b15b77682a875328e023b5b62a9eb2896,PMC,"Update on the Angiotensin Converting Enzyme 2-Angiotensin (1–7)-Mas Receptor Axis: Fetal Programing, Sex Differences, and Intracellular Pathways",http://dx.doi.org/10.3389/fendo.2013.00201,PMC3886117,24409169,CC BY,"The renin-angiotensin-system (RAS) constitutes an important hormonal system in the physiological regulation of blood pressure. Indeed, dysregulation of the RAS may lead to the development of cardiovascular pathologies including kidney injury. Moreover, the blockade of this system by the inhibition of angiotensin converting enzyme (ACE) or antagonism of the angiotensin type 1 receptor (AT(1)R) constitutes an effective therapeutic regimen. It is now apparent with the identification of multiple components of the RAS that the system is comprised of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS can be defined as the ACE-Ang II-AT(1)R axis that promotes vasoconstriction, sodium retention, and other mechanisms to maintain blood pressure, as well as increased oxidative stress, fibrosis, cellular growth, and inflammation in pathological conditions. In contrast, the non-classical RAS composed of the ACE2-Ang-(1–7)-Mas receptor axis generally opposes the actions of a stimulated Ang II-AT(1)R axis through an increase in nitric oxide and prostaglandins and mediates vasodilation, natriuresis, diuresis, and oxidative stress. Thus, a reduced tone of the Ang-(1–7) system may contribute to these pathologies as well. Moreover, the non-classical RAS components may contribute to the effects of therapeutic blockade of the classical system to reduce blood pressure and attenuate various indices of renal injury. The review considers recent studies on the ACE2-Ang-(1–7)-Mas receptor axis regarding the precursor for Ang-(1–7), the intracellular expression and sex differences of this system, as well as an emerging role of the Ang1-(1–7) pathway in fetal programing events and cardiovascular dysfunction.",2014 Jan 9,"['Chappell, Mark C.', 'Marshall, Allyson C.', 'Alzayadneh, Ebaa M.', 'Shaltout, Hossam A.', 'Diz, Debra I.']",Front Endocrinol (Lausanne),,,True
d12f82f17862869b5118dc55c63929adc6597dd4,PMC,"Immunomorphologic Manifestations in Mice Liver Infected with Influenza A/H5N1, A/Goose/Krasnoozerskoye/627/05 Strain",http://dx.doi.org/10.1155/2013/342686,PMC3886489,24454472,CC BY,"Highly pathogenic avian influenza H5N1 (HPAI H5N1) viruses can infect mammals, including humans, causing severe systemic disease with the inhibition of the immune system and a high mortality rate. In conditions of lymphoid tissue depletion, the liver plays an important role in host defence against viruses. The changes in mice liver infected with HPAI H5N1 virus A/goose/Krasnoozerskoye/627/05 have been studied. It has been shown that the virus persistence in the liver leads to the expression of proinflammatory cytokines (TNF-α, IL-6) and intracellular proteases (lysozyme, cathepsin D, and myeloperoxidase) by Kupffer cells. Defective antiviral response exacerbates destructive processes in the liver accelerating the development of liver failure.",2013 Dec 23,"['Potapova, Oxana V.', 'Sharkova, Tatyana V.', 'Shkurupiy, Vyacheslav A.', 'Shestopalov, Alexander M.']",Clin Dev Immunol,,,True
a30fd6139467d0ef97598274d3d926ddf4623e88,PMC,“Don’t forget the migrants”: exploring preparedness and response strategies to combat the potential spread of MERS-CoV virus through migrant workers in Sri Lanka,http://dx.doi.org/10.12688/f1000research.2-163.v1,PMC3886786,24555078,CC BY,"From September 2012 to July 2013, 81 laboratory-confirmed cases of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), including 45 deaths (a case fatality ratio of 55%) have been reported from eight countries. Human-to-human transmission is now confirmed showing potential for another pandemic of zoonotic disease, with an extremely high mortality rate. Effective surveillance strategies are required in countries with a high influx of migrants from the Middle East to mitigate the probable importation of MERS-CoV. We discuss here the risk of MERS-CoV in major labor sending countries and list the probable strategies for control and prevention of MERS-CoV using Sri Lanka as an example. It is conservatively estimated that 10% of Sri Lanka’s population work as international labor migrants (1.8 to 2 million workers), with 93% residing in the Middle East. An average of 720 workers depart each day, with the majority of these workers (71%) departing to the Kingdom of Saudi Arabia (the country with 81.5% of total MERS-CoV cases). We also describe other inbound migration categories such as tourists and resident visa holders relevant to the context of preparedness and planning. The importance of partnerships between public health authorities at national and regional levels with labor migration networks to establish institutional and/or policy mechanisms are highlighted for ensuring effective preparedness and response planning. Strategies that can be taken by public health authorities working in both labor sending and labor receiving counties are also described. The strategies described here may be useful for other labor sending country contexts in Asia with a high frequency and volume of migrant workers to and from the Gulf region.",2013 Jul 29,"['Wickramage, Kolitha', 'Peiris, Sharika', 'Agampodi, Suneth B']",F1000Res,,,True
86bd9005ed7a8aa7f895a9d0769b8dd8e4990e06,PMC,Cell Tropism Predicts Long-term Nucleotide Substitution Rates of Mammalian RNA Viruses,http://dx.doi.org/10.1371/journal.ppat.1003838,PMC3887100,24415935,CC BY,"The high rates of RNA virus evolution are generally attributed to replication with error-prone RNA-dependent RNA polymerases. However, these long-term nucleotide substitution rates span three orders of magnitude and do not correlate well with mutation rates or selection pressures. This substitution rate variation may be explained by differences in virus ecology or intrinsic genomic properties. We generated nucleotide substitution rate estimates for mammalian RNA viruses and compiled comparable published rates, yielding a dataset of 118 substitution rates of structural genes from 51 different species, as well as 40 rates of non-structural genes from 28 species. Through ANCOVA analyses, we evaluated the relationships between these rates and four ecological factors: target cell, transmission route, host range, infection duration; and three genomic properties: genome length, genome sense, genome segmentation. Of these seven factors, we found target cells to be the only significant predictors of viral substitution rates, with tropisms for epithelial cells or neurons (P<0.0001) as the most significant predictors. Further, one-tailed t-tests showed that viruses primarily infecting epithelial cells evolve significantly faster than neurotropic viruses (P<0.0001 and P<0.001 for the structural genes and non-structural genes, respectively). These results provide strong evidence that the fastest evolving mammalian RNA viruses infect cells with the highest turnover rates: the highly proliferative epithelial cells. Estimated viral generation times suggest that epithelial-infecting viruses replicate more quickly than viruses with different cell tropisms. Our results indicate that cell tropism is a key factor in viral evolvability.",2014 Jan 9,"['Hicks, Allison L.', 'Duffy, Siobain']",PLoS Pathog,,,True
cee3dd6c1927b863e94e9493295d99213401f158,PMC,Bat Airway Epithelial Cells: A Novel Tool for the Study of Zoonotic Viruses,http://dx.doi.org/10.1371/journal.pone.0084679,PMC3890267,24454736,CC BY,"Bats have been increasingly recognized as reservoir of important zoonotic viruses. However, until now many attempts to isolate bat-borne viruses in cell culture have been unsuccessful. Further, experimental studies on reservoir host species have been limited by the difficulty of rearing these species. The epithelium of the respiratory tract plays a central role during airborne transmission, as it is the first tissue encountered by viral particles. Although several cell lines from bats were established recently, no well-characterized, selectively cultured airway epithelial cells were available so far. Here, primary cells and immortalized cell lines from bats of the two important suborders Yangochiroptera and Yinpterochiroptera, Carollia perspicillata (Seba's short-tailed bat) and Eidolon helvum (Straw-colored fruit bat), were successfully cultured under standardized conditions from both fresh and frozen organ specimens by cell outgrowth of organ explants and by the use of serum-free primary cell culture medium. Cells were immortalized to generate permanent cell lines. Cells were characterized for their epithelial properties such as expression of cytokeratin and tight junctions proteins and permissiveness for viral infection with Rift-Valley fever virus and vesicular stomatitis virus Indiana. These cells can serve as suitable models for the study of bat-borne viruses and complement cell culture models for virus infection in human airway epithelial cells.",2014 Jan 13,"['Eckerle, Isabella', 'Ehlen, Lukas', 'Kallies, René', 'Wollny, Robert', 'Corman, Victor M.', 'Cottontail, Veronika M.', 'Tschapka, Marco', 'Oppong, Samuel', 'Drosten, Christian', 'Müller, Marcel A.']",PLoS One,,,True
eef61bdfa49b8652fd660b5b8b7e74cf51922505,PMC,Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China,http://dx.doi.org/10.1186/1471-2334-14-21,PMC3890533,24410932,CC BY,"BACKGROUND: This paper reports findings from the prevalence survey conducted in Shandong China in 2010, a province with a population of 94 million. This study aimed to estimate TB prevalence of the province in 2010 in comparison with the 2000 survey; and to compare yields of TB cases from different case finding approaches. METHODS: A population based, cross-sectional survey was conducted using multi-stage random cluster sampling. 54,279 adults participated in the survey with a response rate of 96%. Doctors interviewed and classified participants as suspected TB cases if they presented with persistent cough, abnormal chest X-ray (CXRAY), or both. Three sputum specimens of all suspected cases were collected and sent for smear microscopy and culture. RESULTS: Adjusted prevalence rate of bacteriologically confirmed cases was 34 per 100,000 for adults in Shandong in 2010. Compared to the 2000 survey, TB prevalence has declined by 80%. 53% of bacteriologically confirmed cases did not present persistent cough. The yield of bacteriologically confirmed cases was 47% by symptom screening and 95% by CXRAY. Over 50% of TB cases were among over 65’s. CONCLUSIONS: The prevalence rate of bacteriologically confirmed cases was significantly reduced compared with 2000. The survey raised challenges to identify TB cases without clear symptoms.",2014 Jan 11,"['Wei, Xiaolin', 'Zhang, Xiulei', 'Yin, Jia', 'Walley, John', 'Beanland, Rachel', 'Zou, Guanyang', 'Zhang, Hongmei', 'Li, Fang', 'Liu, Zhimin', 'Zee, Benny CY', 'Griffiths, Sian M']",BMC Infect Dis,,,True
8dab25c25f6598446d3b229d821402278b2bc0b9,PMC,Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling,http://dx.doi.org/10.1186/1471-2164-14-857,PMC3890716,24308360,CC BY,"BACKGROUD: Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. RESULTS: A database of 36,367 unigenes (average length = 1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. CONCLUSIONS: This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb.",2013 Dec 5,"['Chen, Junfeng', 'Dong, Xin', 'Li, Qing', 'Zhou, Xun', 'Gao, Shouhong', 'Chen, Ruibing', 'Sun, Lianna', 'Zhang, Lei', 'Chen, Wansheng']",BMC Genomics,,,True
f5c1542555ee0f8e60c74414e328ed7845b932a4,PMC,Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling,http://dx.doi.org/10.1186/1471-2164-14-857,PMC3890716,24308360,CC BY,"BACKGROUD: Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. RESULTS: A database of 36,367 unigenes (average length = 1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. CONCLUSIONS: This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb.",2013 Dec 5,"['Chen, Junfeng', 'Dong, Xin', 'Li, Qing', 'Zhou, Xun', 'Gao, Shouhong', 'Chen, Ruibing', 'Sun, Lianna', 'Zhang, Lei', 'Chen, Wansheng']",BMC Genomics,,,False
a3b45e62a604fc32b9f370e3e92bb3efc7f5c0b2,PMC,Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling,http://dx.doi.org/10.1186/1471-2164-14-857,PMC3890716,24308360,CC BY,"BACKGROUD: Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. RESULTS: A database of 36,367 unigenes (average length = 1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. CONCLUSIONS: This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb.",2013 Dec 5,"['Chen, Junfeng', 'Dong, Xin', 'Li, Qing', 'Zhou, Xun', 'Gao, Shouhong', 'Chen, Ruibing', 'Sun, Lianna', 'Zhang, Lei', 'Chen, Wansheng']",BMC Genomics,,,False
023e329ab90febccbabdae8e920c2f1bf4c5419f,PMC,Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling,http://dx.doi.org/10.1186/1471-2164-14-857,PMC3890716,24308360,CC BY,"BACKGROUD: Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. RESULTS: A database of 36,367 unigenes (average length = 1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. CONCLUSIONS: This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb.",2013 Dec 5,"['Chen, Junfeng', 'Dong, Xin', 'Li, Qing', 'Zhou, Xun', 'Gao, Shouhong', 'Chen, Ruibing', 'Sun, Lianna', 'Zhang, Lei', 'Chen, Wansheng']",BMC Genomics,,,False
8ea9dbee38148772a4a9701d38358512c3d31a47,PMC,Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling,http://dx.doi.org/10.1186/1471-2164-14-857,PMC3890716,24308360,CC BY,"BACKGROUD: Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. RESULTS: A database of 36,367 unigenes (average length = 1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. CONCLUSIONS: This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb.",2013 Dec 5,"['Chen, Junfeng', 'Dong, Xin', 'Li, Qing', 'Zhou, Xun', 'Gao, Shouhong', 'Chen, Ruibing', 'Sun, Lianna', 'Zhang, Lei', 'Chen, Wansheng']",BMC Genomics,,,False
f7f54aa815c6e0608b2e0ebe3499603926135463,PMC,Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling,http://dx.doi.org/10.1186/1471-2164-14-857,PMC3890716,24308360,CC BY,"BACKGROUD: Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. RESULTS: A database of 36,367 unigenes (average length = 1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. CONCLUSIONS: This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb.",2013 Dec 5,"['Chen, Junfeng', 'Dong, Xin', 'Li, Qing', 'Zhou, Xun', 'Gao, Shouhong', 'Chen, Ruibing', 'Sun, Lianna', 'Zhang, Lei', 'Chen, Wansheng']",BMC Genomics,,,False
217114455f564a37a057840d761b901fd372bef3,PMC,Molecular Detection of Porcine Torovirus in Piglets with Diarrhea in Southwest China,http://dx.doi.org/10.1155/2013/984282,PMC3891532,24459455,CC BY,"Porcine torovirus (PToV) was detected from intestinal samples of piglets with diarrhea from 20 farms in southwest China. The total prevalence of PToV was 45% (9 out of 20 farms); it was the first detection of PToV in China, and also the study analyzed the phylogenetic relationships between the Chinese PToV and PToV reference strains as well as other representative toroviruses. Genetic and phylogenetic analysis showed the existence of genetic diversity among geographically separated PToV. Statistical analysis of the PToV positive rate as well as a survey for other enteric pathogens in diarrheic pigs suggests that PToV may play a role as a causative agent of severe diarrhea in piglets.",2013 Dec 26,"['Zhou, Yuancheng', 'Chen, Lei', 'Zhu, Ling', 'Xu, Zhiwen']",ScientificWorldJournal,,,True
ab906d73fa3fecf440ed8c98ad852397bf7bee1f,PMC,SIRT1 Activating compounds reduce oxidative stress mediated neuronal loss in viral induced CNS demyelinating disease,http://dx.doi.org/10.1186/2051-5960-2-3,PMC3892130,24383546,CC BY,"BACKGROUND: Multiple sclerosis (MS) is characterized by central nervous system inflammation and demyelination, and increasing evidence demonstrates significant neuronal damage also occurs and is associated with permanent functional impairment. Current MS therapies have limited ability to prevent neuronal damage, suggesting additional neuroprotective therapies are needed. Compounds that activate the NAD(+)-dependent SIRT1 deacetylase prevent neuronal loss in an autoimmune-mediated MS model, but the mechanism of this effect is unknown, and it is unclear whether SIRT1 activating compounds exert similar effects in demyelinating disease induced by other etiologies. We measured neuronal loss in C57BL/6 mice inoculated with a neurotropic strain of mouse hepatitis virus, MHV-A59, that induces an MS-like disease. RESULTS: Oral treatment with the SIRT1 activating compound SRTAW04 significantly increased SIRT1 activity within optic nerves and prevented neuronal loss during optic neuritis, an inflammatory demyelinating optic nerve lesion that occurs in MS and its animal models. MHV-A59 induced neuronal loss was associated with reactive oxygen species (ROS) accumulation, and SRTAW04 treatment significantly reduced ROS levels while promoting increased expression of enzymes involved in mitochondrial function and reduction of ROS. SRTAW04 exerted similar protective effects in EAE spinal cords, with decreased demyelination. CONCLUSIONS: Results demonstrate that SIRT1 activating compounds prevent neuronal loss in viral-induced demyelinating disease similar to their effects in autoimmune-mediated disease. One mechanism of this neuroprotective effect involves increasing mitochondrial biogenesis with reduction of oxidative stress. SIRT1 activators represent a potential neuroprotective therapy for MS. Understanding common mechanisms of these effects in distinct disease models will help identify targets for more specific therapies.",2014 Jan 2,"['Khan, Reas S', 'Dine, Kimberly', 'Das Sarma, Jayasri', 'Shindler, Kenneth S']",Acta Neuropathol Commun,,,True
30556242d064131f0f2b645a727d42c55dc1c71e,PMC,"Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren's Syndrome",http://dx.doi.org/10.1155/2013/516516,PMC3892945,24489505,CC BY,"We have previously isolated several IgG rheumatoid factors (RFs) from patients with both rheumatoid arthritis and idiopathic thrombocytopenia purpura using phage display system. To study IgG RFs in patients with other autoimmune diseases, phage display antibody libraries from a hepatitis C virus infected patient with Sjögren's syndrome were constructed. After panning, a specific clone RFL11 was isolated for characterization in advance. The binding activity and specificity of RFL11 to IgG Fc fragment were comparable to those of RFs previously isolated. The analysis with existed RF-Fc complex structures indicated the homology model of RFL11 is similar to IgM RF61 complex with high binding affinity of about 6 × 10(−8) M. This effect resulted from longer complementarity-determining region (CDR) combining key somatic mutations. In the RFL11-Fc interfaces, the CDR-H3 loop forms a finger-like structure extending into the bottom of Fc pocket and resulting in strong ion and cation-pi interactions. Moreover, a process of antigen-driven maturation was proven by somatically mutated VH residues on H2 and H3 CDR loops in the interfaces. Taken together, these results suggested that high affinity IgG RFs can be generated in patients with Sjögren's syndrome and may play an important role in the pathogenesis of this autoimmune disease.",2013 Dec 30,"['Lee, Yu-Ching', 'Tsai, Keng-Chang', 'Leu, Sy-Jye', 'Wang, Tuan-Jen', 'Liu, Chia-Yu', 'Yang, Yi-Yuan']",ScientificWorldJournal,,,True
8ecb2c48d129fe9df101cb136f9496000d4bb581,PMC,Characterization of Angiotensin-Converting Enzyme 2 Ectodomain Shedding from Mouse Proximal Tubular Cells,http://dx.doi.org/10.1371/journal.pone.0085958,PMC3893316,24454948,CC BY,"Angiotensin-converting enzyme 2 (ACE2) is highly expressed in the kidney proximal tubule, where it cleaves angiotensin (Ang) II to Ang-(1-7). Urinary ACE2 levels increase in diabetes, suggesting that ACE2 may be shed from tubular cells. The aim of this study was to determine if ACE2 is shed from proximal tubular cells, to characterize ACE2 fragments, and to study pathways for shedding. Studies involved primary cultures of mouse proximal tubular cells, with ACE2 activity measured using a synthetic substrate, and analysis of ACE2 fragments by immunoblots and mass spectrometry. The culture media from mouse proximal tubular cells demonstrated a time-dependent increase in ACE2 activity, suggesting constitutive ACE2 shedding. ACE2 was detected in media as two bands at ∼90 kDa and ∼70 kDa on immunoblots. By contrast, full-length ACE2 appeared at ∼100 kDa in cell lysates or mouse kidney cortex. Mass spectrometry of the two deglycosylated fragments identified peptides matching mouse ACE2 at positions 18-706 and 18-577, respectively. The C-terminus of the 18-706 peptide fragment contained a non-tryptic site, suggesting that Met(706) is a candidate ACE2 cleavage site. Incubation of cells in high D-glucose (25 mM) (and to a lesser extent Ang II) for 48–72 h increased ACE2 activity in the media (p<0.001), an effect blocked by inhibition of a disintegrin and metalloproteinase (ADAM)17. High D-glucose increased ADAM17 activity in cell lysates (p<0.05). These data indicate that two glycosylated ACE2 fragments are constitutively shed from mouse proximal tubular cells. ACE2 shedding is stimulated by high D-glucose, at least partly via an ADAM17-mediated pathway. The results suggest that proximal tubular shedding of ACE2 may increase in diabetes, which could enhance degradation of Ang II in the tubular lumen, and increase levels of Ang-(1-7).",2014 Jan 15,"['Xiao, Fengxia', 'Zimpelmann, Joseph', 'Agaybi, Samih', 'Gurley, Susan B.', 'Puente, Lawrence', 'Burns, Kevin D.']",PLoS One,,,True
997ebf63461efa3e7cb1fc3014fc957659705202,PMC,Measuring psychological resilience to disasters: are evidence-based indicators an achievable goal?,http://dx.doi.org/10.1186/1476-069X-12-115,PMC3893382,24359448,CC BY,"Despite rising interest on the concept of societal resilience and its measurement, little has been done to provide operational indicators. Importantly, an evidence-based approach to assess the suitability of indicators remains unexplored. Furthermore few approaches that exist do not investigate indicators of psychological resilience, which is emerging as an important component of societal resilience to disasters. Disasters are events which overwhelm local capacities, often producing human losses, injury and damage to the affected communities. As climate hazards and disasters are likely to increase in the coming decades, strengthening the capacity of societies to withstand these shocks and recover quickly is vital. In this review, we search the Web of Knowledge to summarize the evidence on indicators of psychological resilience to disasters and provided a qualitative assessment of six selected studies. We find that an evidence-based approach using features from systematic reviews is useful to compile, select and assess the evidence and elucidate robust indicators. We conclude that strong social support received after a disaster is associated with an increased psychological resilience whereas a female gender is connected with a decrease in the likelihood of a resilient outcome. These results are consistent across disaster settings and cultures and are representative of approximately 13 million disaster-exposed civilians of adult age. An approach such as this that collects and evaluates evidence will allow indicators of resilience to be much more revealing and useful in the future. They will provide a robust basis to prioritize indicators to act upon through intersectoral policies and post-disaster public health interventions.",2013 Dec 20,"['Rodriguez-Llanes, Jose Manuel', 'Vos, Femke', 'Guha-Sapir, Debarati']",Environ Health,,,True
a648c37b99ce3b55b5a07125c086a958bbbf3c13,PMC,A bio-objects approach to biosecurity: the “mutant flu” controversy as a bio-objectification process,http://dx.doi.org/10.3325/cmj.2013.54.592,PMC3893992,24382857,CC BY,,2013 Dec,"Cañada, Jose A.",Croat Med J,,,True
16c14c63746634d9cc1a2d4257b7d7560af187ba,PMC,Alphavirus Mutator Variants Present Host-Specific Defects and Attenuation in Mammalian and Insect Models,http://dx.doi.org/10.1371/journal.ppat.1003877,PMC3894214,24453971,CC BY,"Arboviruses cycle through both vertebrates and invertebrates, which requires them to adapt to disparate hosts while maintaining genetic integrity during genome replication. To study the genetic mechanisms and determinants of these processes, we use chikungunya virus (CHIKV), a re-emerging human pathogen transmitted by the Aedes mosquito. We previously isolated a high fidelity (or antimutator) polymerase variant, C483Y, which had decreased fitness in both mammalian and mosquito hosts, suggesting this residue may be a key molecular determinant. To further investigate effects of position 483 on RNA-dependent RNA-polymerase (RdRp) fidelity, we substituted every amino acid at this position. We isolated novel mutators with decreased replication fidelity and higher mutation frequencies, allowing us to examine the fitness of error-prone arbovirus variants. Although CHIKV mutators displayed no major replication defects in mammalian cell culture, they had reduced specific infectivity and were attenuated in vivo. Unexpectedly, mutator phenotypes were suppressed in mosquito cells and the variants exhibited significant defects in RNA synthesis. Consequently, these replication defects resulted in strong selection for reversion during infection of mosquitoes. Since residue 483 is conserved among alphaviruses, we examined the analogous mutations in Sindbis virus (SINV), which also reduced polymerase fidelity and generated replication defects in mosquito cells. However, replication defects were mosquito cell-specific and were not observed in Drosophila S2 cells, allowing us to evaluate the potential attenuation of mutators in insect models where pressure for reversion was absent. Indeed, the SINV mutator variant was attenuated in fruit flies. These findings confirm that residue 483 is a determinant regulating alphavirus polymerase fidelity and demonstrate proof of principle that arboviruses can be attenuated in mammalian and insect hosts by reducing fidelity.",2014 Jan 16,"['Rozen-Gagnon, Kathryn', 'Stapleford, Kenneth A.', 'Mongelli, Vanesa', 'Blanc, Hervé', 'Failloux, Anna-Bella', 'Saleh, Maria-Carla', 'Vignuzzi, Marco']",PLoS Pathog,,,True
a2d455f2d873e1be7f2db4b069b6e40f3faf168b,PMC,Gammaherpesviral Gene Expression and Virion Composition Are Broadly Controlled by Accelerated mRNA Degradation,http://dx.doi.org/10.1371/journal.ppat.1003882,PMC3894220,24453974,CC BY,"Lytic gammaherpesvirus infection restricts host gene expression by promoting widespread degradation of cytoplasmic mRNA through the activity of the viral endonuclease SOX. Though generally assumed to be selective for cellular transcripts, the extent to which SOX impacts viral mRNA stability has remained unknown. We addressed this issue using the model murine gammaherpesvirus MHV68 and, unexpectedly, found that all stages of viral gene expression are controlled through mRNA degradation. Using both comprehensive RNA expression profiling and half-life studies we reveal that the levels of the majority of viral mRNAs but not noncoding RNAs are tempered by MHV68 SOX (muSOX) activity. The targeting of viral mRNA by muSOX is functionally significant, as it impacts intracellular viral protein abundance and progeny virion composition. In the absence of muSOX-imposed gene expression control the viral particles display increased cell surface binding and entry as well as enhanced immediate early gene expression. These phenotypes culminate in a viral replication defect in multiple cell types as well as in vivo, highlighting the importance of maintaining the appropriate balance of viral RNA during gammaherpesviral infection. This is the first example of a virus that fails to broadly discriminate between cellular and viral transcripts during host shutoff and instead uses the targeting of viral messages to fine-tune overall gene expression.",2014 Jan 16,"['Abernathy, Emma', 'Clyde, Karen', 'Yeasmin, Rukhsana', 'Krug, Laurie T.', 'Burlingame, Al', 'Coscoy, Laurent', 'Glaunsinger, Britt']",PLoS Pathog,,,True
89a3606a8ebb09ebab239030d3ef7082c74b884b,PMC,Gammaherpesviral Gene Expression and Virion Composition Are Broadly Controlled by Accelerated mRNA Degradation,http://dx.doi.org/10.1371/journal.ppat.1003882,PMC3894220,24453974,CC BY,"Lytic gammaherpesvirus infection restricts host gene expression by promoting widespread degradation of cytoplasmic mRNA through the activity of the viral endonuclease SOX. Though generally assumed to be selective for cellular transcripts, the extent to which SOX impacts viral mRNA stability has remained unknown. We addressed this issue using the model murine gammaherpesvirus MHV68 and, unexpectedly, found that all stages of viral gene expression are controlled through mRNA degradation. Using both comprehensive RNA expression profiling and half-life studies we reveal that the levels of the majority of viral mRNAs but not noncoding RNAs are tempered by MHV68 SOX (muSOX) activity. The targeting of viral mRNA by muSOX is functionally significant, as it impacts intracellular viral protein abundance and progeny virion composition. In the absence of muSOX-imposed gene expression control the viral particles display increased cell surface binding and entry as well as enhanced immediate early gene expression. These phenotypes culminate in a viral replication defect in multiple cell types as well as in vivo, highlighting the importance of maintaining the appropriate balance of viral RNA during gammaherpesviral infection. This is the first example of a virus that fails to broadly discriminate between cellular and viral transcripts during host shutoff and instead uses the targeting of viral messages to fine-tune overall gene expression.",2014 Jan 16,"['Abernathy, Emma', 'Clyde, Karen', 'Yeasmin, Rukhsana', 'Krug, Laurie T.', 'Burlingame, Al', 'Coscoy, Laurent', 'Glaunsinger, Britt']",PLoS Pathog,,,False
8806d2b5dd6c0709ed0fc8e99153cbef69fd4614,PMC,Occurrence and phylogenetic analysis of bovine respiratory syncytial virus in outbreaks of respiratory disease in Norway,http://dx.doi.org/10.1186/1746-6148-10-15,PMC3896707,24423030,CC BY,"BACKGROUND: Bovine respiratory syncytial virus (BRSV) is one of the major pathogens involved in the bovine respiratory disease (BRD) complex. The seroprevalence to BRSV in Norwegian cattle herds is high, but its role in epidemics of respiratory disease is unclear. The aims of the study were to investigate the etiological role of BRSV and other respiratory viruses in epidemics of BRD and to perform phylogenetic analysis of Norwegian BRSV strains. RESULTS: BRSV infection was detected either serologically and/or virologically in 18 (86%) of 21 outbreaks and in most cases as a single viral agent. When serology indicated that bovine coronavirus and/or bovine parainfluenza virus 3 were present, the number of BRSV positive animals in the herd was always higher, supporting the view of BRSV as the main pathogen. Sequencing of the G gene of BRSV positive samples showed that the current circulating Norwegian BRSVs belong to genetic subgroup II, along with other North European isolates. One isolate from an outbreak in Norway in 1976 was also investigated. This strain formed a separate branch in subgroup II, clearly different from the current Scandinavian sequences. The currently circulating BRSV could be divided into two different strains that were present in the same geographical area at the same time. The sequence variations between the two strains were in an antigenic important part of the G protein. CONCLUSION: The results demonstrated that BRSV is the most important etiological agent of epidemics of BRD in Norway and that it often acts as the only viral agent. The phylogenetic analysis of the Norwegian strains of BRSV and several previously published isolates supported the theory of geographical and temporal clustering of BRSV.",2014 Jan 14,"['Klem, Thea B', 'Rimstad, Espen', 'Stokstad, Maria']",BMC Vet Res,,,True
b54ab920006bd7dceb8851d37e0eef82d3711534,PMC,Presence of infectious agents and co-infections in diarrheic dogs determined with a real-time polymerase chain reaction-based panel,http://dx.doi.org/10.1186/1746-6148-10-23,PMC3896730,24433321,CC BY,"BACKGROUND: Infectious diarrhea can be caused by bacteria, viruses, or protozoan organisms, or a combination of these. The identification of co-infections in dogs is important to determine the prognosis and to plan strategies for their treatment and prophylaxis. Although many pathogens have been individually detected with real-time polymerase chain reaction (PCR), a comprehensive panel of agents that cause diarrhea in privately owned dogs has not yet been established. The objective of this study was to use a real-time PCR diarrhea panel to survey the frequencies of pathogens and co-infections in owned dogs attended in a veterinary hospital with and without diarrhea, as well the frequency in different countries. Feces samples were tested for canine distemper virus, canine coronavirus, canine parvovirus type 2 (CPV-2), Clostridium perfringens alpha toxin (CPA), Cryptosporidium spp., Giardia spp., and Salmonella spp. using molecular techniques. RESULTS: In total, 104 diarrheic and 43 control dogs that were presented consecutively at a major private veterinary hospital were included in the study. Overall, 71/104 (68.3%) dogs with diarrhea were positive for at least one pathogen: a single infection in 39/71 dogs (54.9%) and co-infections in 32/71 dogs (45.1%), including 21/32 dogs (65.6%) with dual, 5/32 (15.6%) with triple, and 6/32 (18.8%) with quadruple infections. In the control group, 13/43 (30.2%) dogs were positive, all with single infections only. The most prevalent pathogens in the diarrheic dogs were CPA (40/104 dogs, 38.5%), CPV-2 (36/104 dogs, 34.6%), and Giardia spp. (14/104 dogs, 13.5%). CPV-2 was the most prevalent pathogen in the dual co-infections, associated with CPA, Cryptosporidium spp., or Giardia spp. No statistical difference (P = 0.8374) was observed in the duration of diarrhea or the number of deaths (P = 0.5722) in the presence or absence of single or co-infections. CONCLUSIONS: Diarrheic dogs showed a higher prevalence of pathogen infections than the controls. Whereas the healthy dogs had only single infections, about half the diarrheic dogs had co-infections. Therefore, multiple pathogens should be investigated in dogs presenting with diarrhea. The effects of multiple pathogens on the disease outcomes remain unclear because the rate of death and the duration of diarrhea did not seem to be affected by these factors.",2014 Jan 16,"['Gizzi, Aline Baumann da Rocha', 'Oliveira, Simone Tostes', 'Leutenegger, Christian M', 'Estrada, Marko', 'Kozemjakin, Denise Adamczyk', 'Stedile, Rafael', 'Marcondes, Mary', 'Biondo, Alexander Welker']",BMC Vet Res,,,True
304d61d063b602c2971b9df3ce167445c9880645,PMC,A SYBR Green I based real time RT-PCR assay for specific detection and quantitation of Peste des petits ruminants virus,http://dx.doi.org/10.1186/1746-6148-10-22,PMC3896792,24423231,CC BY,"BACKGROUND: Peste des petits ruminants (PPR) is an economically important disease of small ruminants such as sheep and goats. The disease is characterized by severe pyrexia, oculo-nasal discharge, pneumonia, necrosis and ulceration of the mucous membrane and inflammation of the gastro-intestinal tract leading to severe diarrhea. A SYBR Green I based real time RT-PCR targeting the N gene of PPRV has not been established for PPRV detection. Thus, the objective of present study was to develop highly sensitive N gene target SYBR Green I real time RT-PCR for specific detection and quantification of PPRV in clinical samples. A set of primers was designed to detect the nucleocapsid (N) gene of PPRV. RESULTS: The assay exhibited high specificity as all the viruses which have clinical and structural similarities to PPRV including Canine distemper virus (CDV), Measles virus (MV), Bluetongue virus (BTV) and Newcastle disease virus (NDV) failed to show an amplification signal. The lower detection limit of the assay was 5.11 copies/μl (Ct value of 33.67 ± 0.5) and 0.001 TCID(50)/ml (Ct value of 34.7 ± 0.5) based on plasmid copy number and tissue culture infectivity titre. The assay was 3-log more sensitive than the conventional RT-PCR. The coefficient of variation (CV) values for intra- and inter-assay variability were low, ranging from 0.32% - 2.31%, and 0.71% - 5.32%, respectively. To evaluate the performance of the newly developed assay, a total of 36 clinical samples suspected of PPR were screened for the presence of PPRV in parallel with conventional RT-PCR. The real time RT-PCR assay detected PPRV in 30 (83.3%) of clinical samples compared to 16 (44.4%) by conventional RT-PCR. CONCLUSIONS: The two-step SYBR Green I based real time RT-PCR assay reported here is highly sensitive, specific, reproducible and rapid for detection and quantification of PPRV nucleic acids.",2014 Jan 14,"['Abera, Tsegalem', 'Thangavelu, Ardhanary', 'Joy Chandran, Navamani Daniel', 'Raja, Angamuthu']",BMC Vet Res,,,True
09db5b9c6d7c4f5d804c532939fb4f824c409bb6,PMC,Enteropathogen co-infection in UK cats with diarrhoea,http://dx.doi.org/10.1186/1746-6148-10-13,PMC3896830,24410914,CC BY,"BACKGROUND: Individual enteropathogen infections in healthy and clinically ill cats are well described, but prevalence and patterns of enteropathogen co-infection have only been reported on a limited basis. We studied enteropathogen co-infection in diarrhoeic UK cats using results of a real time PCR assay for 8 enteropathogenic species; feline coronavirus (Co), feline panleukopenia virus (Pa), Clostridium perfringens (Cl), Salmonella enterica (Sa), Giardia spp. (Gi), Tritrichomonas foetus (Tr), Cryptosporidium spp. (Cr), and Toxoplasma gondii (To). Age, gender, breed and history were recorded. PCR panels from 1088 diarrhoeic cats were available for analysis. RESULTS: Overall enteropathogen prevalence was 56.9% (Co), 22.1% (Pa), 56.6% (Cl), 0.8% (Sa), 20.6% (Gi), 18.8% (Tr), 24.4% (Cr) and 1.0% (To). Prevalence of Co, Gi and Tr was higher in pedigree cats compared to non-pedigree cats (DSH) and prevalence decreased with increasing age for Co, Pa, Gi, Cr and Tr. Co-infection was common: ≥2 enteropathogens were detected in 62.5% of cats, and 13.3% of cats had ≥4 enteropathogens. Mean ( [Formula: see text]) enteropathogen co-infection 2.01 (±1.3 SD), was significantly higher in pedigree cats ( [Formula: see text] =2.51) compared to DSH ( [Formula: see text] =1.68) and decreased with age ( [Formula: see text] =2.64 <6 months, [Formula: see text] =1.68 for >1 yr). More cats were negative for all 8 enteropathogens tested (12.7%) than expected. When exact combinations of co-infection were examined, Tr tended to be found in combinations with Co, Cl, and Gi. CONCLUSIONS: Multiple infections should be considered the most likely result of faecal testing in cats, and case management needs to take this into account. In contrast, the relatively high percentage of cats negative for all 8 enteropathogens tested could indicate an innate resistance to infection. Alternatively it could indicate a lack of exposure to these 8 enteropathogens or the presence of other enteropathogens not assessed by this assay.",2014 Jan 12,"['Paris, Jasmin K', 'Wills, Sheila', 'Balzer, Hans-Jörg', 'Shaw, Darren J', 'Gunn-Moore, Danièlle A']",BMC Vet Res,,,True
5bc5b2f9dee2ff454efe226384070d467112e25d,PMC,A 2D graphical representation of the sequences of DNA based on triplets and its application,http://dx.doi.org/10.1186/1687-4153-2014-1,PMC3896961,24383852,CC BY,"In this paper, we first present a new concept of ‘weight’ for 64 triplets and define a different weight for each kind of triplet. Then, we give a novel 2D graphical representation for DNA sequences, which can transform a DNA sequence into a plot set to facilitate quantitative comparisons of DNA sequences. Thereafter, associating with a newly designed measure of similarity, we introduce a novel approach to make similarities/dissimilarities analysis of DNA sequences. Finally, the applications in similarities/dissimilarities analysis of the complete coding sequences of β-globin genes of 11 species illustrate the utilities of our newly proposed method.",2014 Jan 2,"['Zou, Sai', 'Wang, Lei', 'Wang, Junfeng']",EURASIP J Bioinform Syst Biol,,,True
639215bc06ff8518135073d907b7bf6a9089c1fc,PMC,AAV Vectors Vaccines Against Infectious Diseases,http://dx.doi.org/10.3389/fimmu.2014.00005,PMC3896988,24478774,CC BY,"Since their discovery as a tool for gene transfer, vectors derived from the adeno-associated virus (AAV) have been used for gene therapy applications and attracted scientist to this field for their exceptional properties of efficiency of in vivo gene transfer and the level and duration of transgene expression. For many years, AAVs have been considered as low immunogenic vectors due to their ability to induce long-term expression of non-self-proteins in contrast to what has been observed with other viral vectors, such as adenovirus, for which strong immune responses against the same transgene products were documented. The perceived low immunogenicity likely explains why the use of AAV vectors for vaccination was not seriously considered before the early 2000s. Indeed, while analyses conducted using a variety of transgenes and animal species slowly changed the vision of immunological properties of AAVs, an increasing number of studies were also performed in the field of vaccination. Even if the comparison with other modes of vaccination was not systemically performed, the analyses conducted so far in the field of active immunotherapy strongly suggest that AAVs possess some interesting features to be used as tools to produce an efficient and sustained antibody response. In addition, recent studies also highlighted the potential of AAVs for passive immunotherapy. This review summarizes the main studies conducted to evaluate the potential of AAV vectors for vaccination against infectious agents and discusses their advantages and drawbacks. Altogether, the variety of studies conducted in this field contributes to the understanding of the immunological properties of this versatile virus and to the definition of its possible future applications.",2014 Jan 21,"['Nieto, Karen', 'Salvetti, Anna']",Front Immunol,,,True
d17ba127439d63e04c399c19a06fa63998d65e6d,PMC,Immunosuppressive Drugs Modulate the Replication of Hepatitis B Virus (HBV) in a Hydrodynamic Injection Mouse Model,http://dx.doi.org/10.1371/journal.pone.0085832,PMC3897536,24465734,CC BY,"Hepatitis B virus (HBV) reactivation and recurrence are common in patients under immunosuppression and can be controlled by hepatitis B immunoglobulin, antivirals, and hepatitis B vaccine. However, the detailed analysis of HBV infection under immunosuppression is essential for the prophylaxis and therapy for HBV reactivation and recurrence. In this study, HBV replication and T cell responses were analyzed in a HBV-transfected mouse model under immunosuppressive therapy. During the treatment, HBV replication was at a high level in mice treated with dexamethasone, cyclosporine, and cyclophosphamide, whereas was terminated in mice treated with mycophenolate mofetil. After the withdrawal, HBV replication was at low or high levels in the dexamethasone-treated mice or in both cyclosporine- and cyclophosphamide-treated mice. The early withdrawal of cyclosporine allowed the recovery of suppressed T cell responses and led to subsequent HBV clearance, while the adoptive immune transfer to the mice with HBV persistence led to HBV suppression. Taken together, long-term HBV persistence under immunosuppression depends on the immunosuppressive drugs used and on the treatment duration and is mediated by the suppressed intrahepatic CD8 T cell response. These data may be helpful for individualized immunosuppressive therapy in patients with high risk of HBV reactivation and recurrence, and the mouse system is suitable for studying HBV reactivation and recurrence under immunosuppression.",2014 Jan 21,"['Wang, Junzhong', 'Wang, Baoju', 'Huang, Shunmei', 'Song, Zhitao', 'Wu, Jun', 'Zhang, Ejuan', 'Zhu, Zhenni', 'Zhu, Bin', 'Yin, Ying', 'Lin, Yong', 'Xu, Yang', 'Zheng, Xin', 'Lu, Mengji', 'Yang, Dongliang']",PLoS One,,,True
da412bad3772b82d1b3ab2d1aa1e00035869ac55,PMC,"Nasal swab samples and real-time polymerase chain reaction assays in community-based, longitudinal studies of respiratory viruses: the importance of sample integrity and quality control",http://dx.doi.org/10.1186/1471-2334-14-15,PMC3897990,24405747,CC BY,"BACKGROUND: Carefully conducted, community-based, longitudinal studies are required to gain further understanding of the nature and timing of respiratory viruses causing infections in the population. However, such studies pose unique challenges for field specimen collection, including as we have observed the appearance of mould in some nasal swab specimens. We therefore investigated the impact of sample collection quality and the presence of visible mould in samples upon respiratory virus detection by real-time polymerase chain reaction (PCR) assays. METHODS: Anterior nasal swab samples were collected from infants participating in an ongoing community-based, longitudinal, dynamic birth cohort study. The samples were first collected from each infant shortly after birth and weekly thereafter. They were then mailed to the laboratory where they were catalogued, stored at -80°C and later screened by PCR for 17 respiratory viruses. The quality of specimen collection was assessed by screening for human deoxyribonucleic acid (DNA) using endogenous retrovirus 3 (ERV3). The impact of ERV3 load upon respiratory virus detection and the impact of visible mould observed in a subset of swabs reaching the laboratory upon both ERV3 loads and respiratory virus detection was determined. RESULTS: In total, 4933 nasal swabs were received in the laboratory. ERV3 load in nasal swabs was associated with respiratory virus detection. Reduced respiratory virus detection (odds ratio 0.35; 95% confidence interval 0.27-0.44) was observed in samples where the ERV3 could not be identified. Mould was associated with increased time of samples reaching the laboratory and reduced ERV3 loads and respiratory virus detection. CONCLUSION: Suboptimal sample collection and high levels of visible mould can impact negatively upon sample quality. Quality control measures, including monitoring human DNA loads using ERV3 as a marker for epithelial cell components in samples should be undertaken to optimize the validity of real-time PCR results for respiratory virus investigations in community-based studies.",2014 Jan 9,"['Alsaleh, Asma N', 'Whiley, David M', 'Bialasiewicz, Seweryn', 'Lambert, Stephen B', 'Ware, Robert S', 'Nissen, Michael D', 'Sloots, Theo P', 'Grimwood, Keith']",BMC Infect Dis,,,True
eae06fd0ce129fbfb73f70fd0c49df18c40632dd,PMC,Thank you to Virology Journal's peer reviewers in 2013,http://dx.doi.org/10.1186/1743-422X-11-4,PMC3898089,,CC BY,"The editors of Virology Journal would like to thank all our reviewers who have contributed to the journal in Volume 10 (2013). The success of any scientific journal depends on an effective and strict peer review process and Virology Journal could not operate without your contribution. We are grateful to the large number of reviewers (1026 to be exact!), who have done a great job in not only lifting the quality of the journal’s scientific peer reviewing process, but also helped us to achieve our goal of a median time to first decision of just 35 days. Our record time from submission to online, open access, publication in 2013 was 22 days for a Research Article [1] and 28 days for a Review [2]. This is a great achievement by any standard. We look forward to your continuous support of Virology Journal either as an invited reviewer or a contributing author in the years to come.",2014 Jan 22,"Wang, Linfa",Virol J,,,True
2b2e83d49677c03c836133b83b909f5db0423cc9,PMC,Development of a novel clinical scoring system for on-farm diagnosis of bovine respiratory disease in pre-weaned dairy calves,http://dx.doi.org/10.7717/peerj.238,PMC3898311,24482759,CC BY,"Several clinical scoring systems for diagnosis of bovine respiratory disease (BRD) in calves have been proposed. However, such systems were based on subjective judgment, rather than statistical methods, to weight scores. Data from a pair-matched case-control study on a California calf raising facility was used to develop three novel scoring systems to diagnose BRD in preweaned dairy calves. Disease status was assigned using both clinical signs and diagnostic test results for BRD-associated pathogens. Regression coefficients were used to weight score values. The systems presented use nasal and ocular discharge, rectal temperature, ear and head carriage, coughing, and respiratory quality as predictors. The systems developed in this research utilize fewer severity categories of clinical signs, require less calf handling, and had excellent agreement (Kappa > 0.8) when compared to an earlier scoring system. The first scoring system dichotomized all clinical predictors but required inducing a cough. The second scoring system removed induced cough as a clinical abnormality but required distinguishing between three levels of nasal discharge severity. The third system removed induced cough and forced a dichotomized variable for nasal discharge. The first system presented in this study used the following predictors and assigned values: coughing (induced or spontaneous coughing, 2 points), nasal discharge (any discharge, 3 points), ocular discharge (any discharge, 2 points), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C or 102.5°F, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized “BRD positive” if their total score was ≥4. This system correctly classified 95.4% cases and 88.6% controls. The second presented system categorized the predictors and assigned weights as follows: coughing (spontaneous only, 2 points), mild nasal discharge (unilateral, serous, or watery discharge, 3 points), moderate to severe nasal discharge (bilateral, cloudy, mucoid, mucopurlent, or copious discharge, 5 points), ocular discharge (any discharge, 1 point), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized “BRD positive” if their total score was ≥4. This system correctly classified 89.3% cases and 92.8% controls. The third presented system used the following predictors and scores: coughing (spontaneous only, 2 points), nasal discharge (any, 4 points), ocular discharge (any, 2 points), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized “BRD positive” if their total score was ≥5. This system correctly classified 89.4% cases and 90.8% controls. Each of the proposed systems offer few levels of clinical signs and data-based weights for on-farm diagnosis of BRD in dairy calves.",2014 Jan 2,"['Love, William J.', 'Lehenbauer, Terry W.', 'Kass, Philip H.', 'Van Eenennaam, Alison L.', 'Aly, Sharif S.']",PeerJ,,,True
0a4a2763f35864555a20b296c1daf1614f09e28f,PMC,In Vitro and In Vivo Activity of a Novel Antifungal Small Molecule against Candida Infections,http://dx.doi.org/10.1371/journal.pone.0085836,PMC3899067,24465737,CC BY,"Candida is the most common fungal pathogen of humans worldwide and has become a major clinical problem because of the growing number of immunocompromised patients, who are susceptible to infection. Moreover, the number of available antifungals is limited, and antifungal-resistant Candida strains are emerging. New and effective antifungals are therefore urgently needed. Here, we discovered a small molecule with activity against Candida spp. both in vitro and in vivo. We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. This screening identified 20 active compounds. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC) 0.2 – 1.6 µg/ml). In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Moreover, SM21 was relatively more effective against biofilms of Candida spp. than the current antifungal agents. In vivo, SM21 prevented the death of mice in a systemic candidiasis model and was also more effective than the common antifungal nystatin at reducing the extent of tongue lesions in a mouse model of oral candidiasis. Propidium iodide uptake assay showed that SM21 affected the integrity of the cell membrane. Taken together, our results indicate that SM21 has the potential to be developed as a novel antifungal agent for clinical use.",2014 Jan 22,"['Wong, Sarah Sze Wah', 'Kao, Richard Yi Tsun', 'Yuen, Kwok Yong', 'Wang, Yu', 'Yang, Dan', 'Samaranayake, Lakshman Perera', 'Seneviratne, Chaminda Jayampath']",PLoS One,,,True
8605d9a84e827e232a47861c65c61605c789acf7,PMC,Transmission of Pandemic Influenza A (H1N1) Virus in a Train in China,http://dx.doi.org/10.2188/jea.JE20100119,PMC3899419,21646746,CC BY,"BACKGROUND: Pandemic influenza A (H1N1) virus emerged in North America in April 2009 and spread globally. We describe the epidemiology and public health response to the first known outbreak of 2009 H1N1 in a train, which occurred in June 2009 in China. METHODS: After 2 provinces provided initial reports of 2009 H1N1 infection in 2 persons who had travelled on the same train, we conducted a retrospective epidemiologic investigation to collect information from the passengers, crew members, contacts, and health care providers. We explored the source of infection and possible routes of transmission in the train. All cases were confirmed by real-time reverse transcription polymerase chain reaction testing. RESULTS: Train #1223 traveled 40 hours, made 28 stops in 4 Chinese provinces, and boarded 2555 passengers, who logged a total of 59 144 person-hours of travel time. Nineteen confirmed 2009 H1N1 cases were identified. Of these, 13 were infected and developed symptoms on the train and 6 occurred among contacts who developed illness during medical monitoring. In addition, 3 asymptomatic cases were identified based on RT-PCR testing of respiratory swabs from contacts. The attack rate among contacts of confirmed cases in the same car was higher than that among contacts in other cars (3.15% vs. 0%, P < 0.001). Attack rates increased with exposure time. CONCLUSIONS: Close contact and long exposure may have contributed to the transmission of 2009 H1N1 virus in the train. Trains may have played an important role in the 2009 influenza pandemic.",2011 Jul 5,"['Cui, Fuqiang', 'Luo, Huiming', 'Zhou, Lei', 'Yin, Dapeng', 'Zheng, Canjun', 'Wang, Dingming', 'Gong, Jian', 'Fang, Gang', 'He, Jianfeng', 'McFarland, Jeffrey', 'Yu, Hongjie']",J Epidemiol,,,True
c8b1da52eeb1d7dc2ff2f2f20a44ef13160fd626,PMC,Sambucus nigra extracts inhibit infectious bronchitis virus at an early point during replication,http://dx.doi.org/10.1186/1746-6148-10-24,PMC3899428,24433341,CC BY,"BACKGROUND: Infectious bronchitis virus (IBV) is a pathogenic chicken coronavirus. Currently, vaccination against IBV is only partially protective; therefore, better preventions and treatments are needed. Plants produce antimicrobial secondary compounds, which may be a source for novel anti-viral drugs. Non-cytotoxic, crude ethanol extracts of Rhodiola rosea roots, Nigella sativa seeds, and Sambucus nigra fruit were tested for anti-IBV activity, since these safe, widely used plant tissues contain polyphenol derivatives that inhibit other viruses. RESULTS: Dose–response cytotoxicity curves on Vero cells using trypan blue staining determined the highest non-cytotoxic concentrations of each plant extract. To screen for IBV inhibition, cells and virus were pretreated with extracts, followed by infection in the presence of extract. Viral cytopathic effect was assessed visually following an additional 24 h incubation with extract. Cells and supernatants were harvested separately and virus titers were quantified by plaque assay. Variations of this screening protocol determined the effects of a number of shortened S. nigra extract treatments. Finally, S. nigra extract-treated virions were visualized by transmission electron microscopy with negative staining. Virus titers from infected cells treated with R. rosea and N. sativa extracts were not substantially different from infected cells treated with solvent alone. However, treatment with S. nigra extracts reduced virus titers by four orders of magnitude at a multiplicity of infection (MOI) of 1 in a dose-responsive manner. Infection at a low MOI reduced viral titers by six orders of magnitude and pretreatment of virus was necessary, but not sufficient, for full virus inhibition. Electron microscopy of virions treated with S. nigra extract showed compromised envelopes and the presence of membrane vesicles, which suggested a mechanism of action. CONCLUSIONS: These results demonstrate that S. nigra extract can inhibit IBV at an early point in infection, probably by rendering the virus non-infectious. They also suggest that future studies using S. nigra extract to treat or prevent IBV or other coronaviruses are warranted.",2014 Jan 16,"['Chen, Christie', 'Zuckerman, David M', 'Brantley, Susanna', 'Sharpe, Michka', 'Childress, Kevin', 'Hoiczyk, Egbert', 'Pendleton, Amanda R']",BMC Vet Res,,,True
45f6818a37c16f974f9be1d2e94e0ff5b9887c4d,PMC,"Attitudes, practices and information needs regarding novel influenza A (H7N9) among employees of food production and operation in Guangzhou, Southern China: a cross-sectional study",http://dx.doi.org/10.1186/1471-2334-14-4,PMC3899619,24383626,CC BY,"BACKGROUND: As of 30 May 2013, 132 human infections with avian influenza A (H7N9) had been reported in 10 Chinese cities. On 17 May 2013, because a chicken infection with H7 subtype avian influenza virus was detected in Guanzhou, Guangzhou became the 11th city to conduct emergency response operations. The goal of this study was to identify attitudes, practices and information needs among employees of food production and operation in Guangzhou. METHODS: A cross-sectional survey of face-to-face interviews was used during 17–24 June 2013. All adults seeking health examination in Guangzhou Center for Disease Control and Prevention who had lived in Guangzhou for at least 3 months, were engaged in food production and operation, and agreed to participate were interviewed. RESULTS: Of 1,450 participants, 69.72% worried about being infected with the A/H7N9 and 74.41% stated that they had searched for information about A/H7N9. The internet (76.92%), television (67.56%), and newspapers (56.26%) were the main methods of obtaining information; the use of these methods differed significantly by various demographic variables (P < 0.05). More than one-fifth of participants complained that the information was not timely enough (20.28%) and was intentionally concealed by the government (20.76%). Nearly one-third (32.35%) did not believe that the government could control the A/H7N9 epidemic. Most participants (80.76%) reported washing hands more frequently than before, while over one-third (37.17%) stated no longer buying poultry. A total of 84.00% indicated a willingness to receive an A/H7N9 vaccine, and the primary reason for not being willing was concern about safety (58.19%). A history of influenza vaccination and worry about being infected with the A/H7N9 were significantly associated with intention to receive an A/H7N9 vaccine (P < 0.05). CONCLUSIONS: Our findings provide insight into the attitudes and practices of employees of food production and operation 3 months after the first human A/H7N9 case reported in China, and 1 month after infected chickens were identified in Guangzhou. Distrust in the health department should be addressed, and more effort should be made to improve compliance of proper preventive measures to reduce panic among the public. The information needs should be taken into account in the next step of health education.",2014 Jan 2,"['Li, Tiegang', 'Feng, Jing', 'Qing, Pengzhe', 'Fan, Xiaomei', 'Liu, Weisi', 'Li, MeiXia', 'Wang, Ming']",BMC Infect Dis,,,True
48f553c843618f0cc189f9067685f551049a018f,PMC,Bayesian Reconstruction of Disease Outbreaks by Combining Epidemiologic and Genomic Data,http://dx.doi.org/10.1371/journal.pcbi.1003457,PMC3900386,24465202,CC BY,"Recent years have seen progress in the development of statistically rigorous frameworks to infer outbreak transmission trees (“who infected whom”) from epidemiological and genetic data. Making use of pathogen genome sequences in such analyses remains a challenge, however, with a variety of heuristic approaches having been explored to date. We introduce a statistical method exploiting both pathogen sequences and collection dates to unravel the dynamics of densely sampled outbreaks. Our approach identifies likely transmission events and infers dates of infections, unobserved cases and separate introductions of the disease. It also proves useful for inferring numbers of secondary infections and identifying heterogeneous infectivity and super-spreaders. After testing our approach using simulations, we illustrate the method with the analysis of the beginning of the 2003 Singaporean outbreak of Severe Acute Respiratory Syndrome (SARS), providing new insights into the early stage of this epidemic. Our approach is the first tool for disease outbreak reconstruction from genetic data widely available as free software, the R package outbreaker. It is applicable to various densely sampled epidemics, and improves previous approaches by detecting unobserved and imported cases, as well as allowing multiple introductions of the pathogen. Because of its generality, we believe this method will become a tool of choice for the analysis of densely sampled disease outbreaks, and will form a rigorous framework for subsequent methodological developments.",2014 Jan 23,"['Jombart, Thibaut', 'Cori, Anne', 'Didelot, Xavier', 'Cauchemez, Simon', 'Fraser, Christophe', 'Ferguson, Neil']",PLoS Comput Biol,,,True
1e3bb33ad4578e3e176b4c68fc4903d6541d9e80,PMC,Bayesian Reconstruction of Disease Outbreaks by Combining Epidemiologic and Genomic Data,http://dx.doi.org/10.1371/journal.pcbi.1003457,PMC3900386,24465202,CC BY,"Recent years have seen progress in the development of statistically rigorous frameworks to infer outbreak transmission trees (“who infected whom”) from epidemiological and genetic data. Making use of pathogen genome sequences in such analyses remains a challenge, however, with a variety of heuristic approaches having been explored to date. We introduce a statistical method exploiting both pathogen sequences and collection dates to unravel the dynamics of densely sampled outbreaks. Our approach identifies likely transmission events and infers dates of infections, unobserved cases and separate introductions of the disease. It also proves useful for inferring numbers of secondary infections and identifying heterogeneous infectivity and super-spreaders. After testing our approach using simulations, we illustrate the method with the analysis of the beginning of the 2003 Singaporean outbreak of Severe Acute Respiratory Syndrome (SARS), providing new insights into the early stage of this epidemic. Our approach is the first tool for disease outbreak reconstruction from genetic data widely available as free software, the R package outbreaker. It is applicable to various densely sampled epidemics, and improves previous approaches by detecting unobserved and imported cases, as well as allowing multiple introductions of the pathogen. Because of its generality, we believe this method will become a tool of choice for the analysis of densely sampled disease outbreaks, and will form a rigorous framework for subsequent methodological developments.",2014 Jan 23,"['Jombart, Thibaut', 'Cori, Anne', 'Didelot, Xavier', 'Cauchemez, Simon', 'Fraser, Christophe', 'Ferguson, Neil']",PLoS Comput Biol,,,False
83a6a45a591e9222cf68f14d60dce7d3c810c1f0,PMC,Resting of Cryopreserved PBMC Does Not Generally Benefit the Performance of Antigen-Specific T Cell ELISPOT Assays,http://dx.doi.org/10.3390/cells1030409,PMC3901103,24710483,CC BY,"T cell monitoring is increasingly performed using cryopreserved PBMC. It has been suggested that resting of PBMC after thawing, that is, culturing them overnight in test medium, produces higher antigen-induced spot counts in ELISPOT assays. To evaluate the importance of overnight resting, we systematically tested cryopreserved PBMC from 25 healthy donors. CEF peptides (comprising CMV, EBV and flu antigens) were used to stimulate CD8 cells and mumps antigen to stimulate CD4 cells. The data show that resting significantly increased antigen-elicited T cell responses only for CEF high responder PBMC. The maximal gain observed was doubling of spot counts. For CEF low responders, and for mumps responders of either low- or high reactivity levels, resting had no statistically significant effect on the observed spot counts. Therefore, resting is not a generally applicable approach to improve ELISPOT assay performance, but can be recommended only for clinical subject cohorts and antigens for which it has a proven benefit. Because resting invariably leads to losing about half of the PBMC available for testing, and because doubling the PBMC numbers plated into the assay reliably doubles the antigen-induced spot counts, we suggest the latter approach as a simple and reliable alternative to resting for enhancing the performance of ELISPOT assays. Our data imply that resting is not required if PBMC were cryopreserved and thawed under conditions that minimize apoptosis of the cells. Therefore, this study should draw attention to the need to optimize freezing and thawing conditions for successful T cell work.",2012 Jul 30,"['Kuerten, Stefanie', 'Batoulis, Helena', 'Recks, Mascha S.', 'Karacsony, Edith', 'Zhang, Wenji', 'Subbramanian, Ramu A.', 'Lehmann, Paul V.']",Cells,,,True
14898820328acb4f3dcf85f33f3addb113d5a97d,PMC,Modulation of Autophagy-Like Processes by Tumor Viruses,http://dx.doi.org/10.3390/cells1030204,PMC3901111,24710474,CC BY,"Autophagy is an intracellular degradation pathway for long-lived proteins and organelles. This process is activated above basal levels upon cell intrinsic or environmental stress and dysregulation of autophagy has been linked to various human diseases, including those caused by viral infection. Many viruses have evolved strategies to directly interfere with autophagy, presumably to facilitate their replication or to escape immune detection. However, in some cases, modulation of autophagy appears to be a consequence of the virus disturbing the cell’s metabolic signaling networks. Here, we summarize recent advances in research at the interface of autophagy and viral infection, paying special attention to strategies that human tumor viruses have evolved.",2012 Jun 25,"['Mack, Hildegard I. D.', 'Munger, Karl']",Cells,,,True
4a64ef9057367aec43ce6b8a40e9bb0c9587fdf4,PMC,Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats,http://dx.doi.org/10.3390/cells1041168,PMC3901151,24710549,CC BY,"Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH). Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture.",2012 Dec 5,"['Zhang, Qing', 'Miller, Christopher', 'Bible, Jesse', 'Li, Jiliang', 'Xu, Xiaoqing', 'Mehta, Nozer', 'Gilligan, James', 'Vignery, Agnès', 'Scholz, Jodi A Carlson']",Cells,,,True
89e039e0e861069bedfb158e43844d3730b5abbb,PMC,Functional Polymorphisms of Interferon-gamma Affect Pneumonia-Induced Sepsis,http://dx.doi.org/10.1371/journal.pone.0087049,PMC3901723,24475220,CC BY,"OBJECTIVE: Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-γ) plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs) that may be associated with sepsis. METHODS: A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation) and SOFA (sepsis-related organ failure assessment) scores and discharge rate. Four functional SNPs, −1616T/C (rs2069705), −764G/C (rs2069707), +874A/T (rs2430561) and +3234C/T (rs2069718), were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson’s chi-square test or Fisher’s exact test were used to analyze the distribution of the SNPs, and the probability values (P values), odds ratios (OR) and 95% confidence intervals (CIs) were calculated. RESULTS: No mutations in the IFN-γ −764G/C SNP were detected among the participants in our study. The +874A/T and +3234C/T SNPs were in strong linkage disequilibrium (LD) (r(2) = 0.894). The −1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence. Genotype of −1616 TT wasn’t only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC. The TAC haplotype was was protective against progression to severe sepsis either. CONCLUSION: Our results suggest that functional IFN-γ SNPs and their haplotypes are associated with pneumonia-induced sepsis.",2014 Jan 24,"['Wang, Ding', 'Zhong, Xuan', 'Huang, Dongjian', 'Chen, Rui', 'Bai, Guibin', 'Li, Qing', 'Yu, Bolan', 'Fan, Yong', 'Sun, Xiaofang']",PLoS One,,,True
b010b3bb7db4f358b0ec2829523ccbfd6d52afbc,PMC,Cost-effective length and timing of school closure during an influenza pandemic depend on the severity,http://dx.doi.org/10.1186/1742-4682-11-5,PMC3901768,24447310,CC BY,"BACKGROUND: There has been a variation in published opinions toward the effectiveness of school closure which is implemented reactively when substantial influenza transmissions are seen at schools. Parameterizing an age-structured epidemic model using published estimates of the pandemic H1N1-2009 and accounting for the cost effectiveness, we examined if the timing and length of school closure could be optimized. METHODS: Age-structured renewal equation was employed to describe the epidemic dynamics of an influenza pandemic. School closure was assumed to take place only once during the course of the pandemic, abruptly reducing child-to-child transmission for a fixed length of time and also influencing the transmission between children and adults. Public health effectiveness was measured by reduction in the cumulative incidence, and cost effectiveness was also examined by calculating the incremental cost effectiveness ratio and adopting a threshold of 1.0 × 10(7) Japanese Yen/life-year. RESULTS: School closure at the epidemic peak appeared to yield the largest reduction in the final size, while the time of epidemic peak was shown to depend on the transmissibility. As the length of school closure was extended, we observed larger reduction in the cumulative incidence. Nevertheless, the cost effectiveness analysis showed that the cost of our school closure scenario with the parameters derived from H1N1-2009 was not justifiable. If the risk of death is three times or greater than that of H1N1-2009, the school closure could be regarded as cost effective. CONCLUSIONS: There is no fixed timing and duration of school closure that can be recommended as universal guideline for different types of influenza viruses. The effectiveness of school closure depends on the transmission dynamics of a particular influenza virus strain, especially the virulence (i.e. the infection fatality risk).",2014 Jan 21,"['Nishiura, Hiroshi', 'Ejima, Keisuke', 'Mizumoto, Kenji', 'Nakaoka, Shinji', 'Inaba, Hisashi', 'Imoto, Seiya', 'Yamaguchi, Rui', 'Saito, Masaya M']",Theor Biol Med Model,,,True
e141a069b6f6aef31ddf1a2ae592933db0b4a031,PMC,Discovery of functional genomic motifs in viruses with ViReMa–a Virus Recombination Mapper–for analysis of next-generation sequencing data,http://dx.doi.org/10.1093/nar/gkt916,PMC3902915,24137010,CC BY,"We developed an algorithm named ViReMa (Viral-Recombination-Mapper) to provide a versatile platform for rapid, sensitive and nucleotide-resolution detection of recombination junctions in viral genomes using next-generation sequencing data. Rather than mapping read segments of pre-defined lengths and positions, ViReMa dynamically generates moving read segments. ViReMa initially attempts to align the 5′ end of a read to the reference genome(s) with the Bowtie seed-based alignment. A new read segment is then made by either extracting any unaligned nucleotides at the 3′ end of the read or by trimming the first nucleotide from the read. This continues iteratively until all portions of the read are either mapped or trimmed. With multiple reference genomes, it is possible to detect virus-to-host or inter-virus recombination. ViReMa is also capable of detecting insertion and substitution events and multiple recombination junctions within a single read. By mapping the distribution of recombination events in the genome of flock house virus, we demonstrate that this information can be used to discover de novo functional motifs located in conserved regions of the viral genome.",2014 Jan 9,"['Routh, Andrew', 'Johnson, John E.']",Nucleic Acids Res,,,True
7d8f6f7c012e065e971832e990bcf5b9b5bc6928,PMC,High-Throughput Screening to Identify Plant Derived Human LDH-A Inhibitors,,PMC3903096,24478981,CC BY,"AIMS: Lactate dehydrogenase (LDH)-A is highly expressed in diverse human malignant tumors, parallel to aggressive metastatic disease, resistance to radiation/chemotherapy and clinically poor outcome. Although this enzyme constitutes a plausible target in treatment of advanced cancer, there are few known LDH-A inhibitors. STUDY DESIGN: In this work, we utilized a high-throughput enzyme micro-array format to screen and evaluate > 900 commonly used medicinal plant extracts (0.00001-.5 mg/ml) for capacity to inhibit activity of recombinant full length human LDHA; EC .1.1.1.27. METHODOLOGY: The protein sequence of purified enzyme was confirmed using 1D gel electrophoresis- MALDI-TOF-MS/MS, enzyme activity was validated by oxidation of NADH (500μM) and kinetic inhibition established in the presence of a known inhibitor (Oxalic Acid). RESULTS: Of the natural extracts tested, the lowest IC(50)s [<0.001 mg/ml] were obtained by: Chinese Gallnut (Melaphis chinensis gallnut), Bladderwrack (Fucus vesiculosus), Kelp (Laminaria Japonica) and Babul (Acacia Arabica). Forty-six additional herbs contained significant LDH-A inhibitory properties with IC(50)s [<0.07 mg/ml], some of which have common names of Arjun, Pipsissewa, Cinnamon, Pink Rose Buds/Petals, Wintergreen, Cat’s Claw, Witch Hazel Root and Rhodiola Root. CONCLUSION: These findings reflect relative potency by rank of commonly used herbs and plants that contain human LDH-A inhibitory properties. Future research will be required to isolate chemical constituents within these plants responsible for LDH-A inhibition and investigate potential therapeutic application.",2013,"['Deiab, S.', 'Mazzio, E.', 'Messeha, S.', 'Mack, N.', 'Soliman, K. F. A.']",European J Med Plants,,,True
f18489a27432115deff5b9be2dd2e0af9d8409a5,PMC,Comparison of Road Traffic Injury Characteristics between Local versus Floating Migrant Patients in a Tertiary Hospital between 2007 and 2010,http://dx.doi.org/10.1371/journal.pone.0082640,PMC3903469,24475023,CC BY,"BACKGROUND: The aim of this study is to give a description of the road traffic injuries (RTIs) characteristics of floating migrant population by comparing with those of local residents in a harbor city of China. METHODS: A population-based descriptive study was carried out between 2007 and 2010 with RTI patient records from the Fifth Center Hospital of Tianjin. Inpatient diagnoses of RTI patients were defined using the International Classification of Diseases, Tenth Revision (ICD-10) codes. We analyzed the demographics and general characteristics of RTI patients that were in the hospital during the four years. In order to compare the group differences between local resident patients and floating migrant patients, the distribution of their ages, diagnoses, severity of injuries, duration of inpatient stays, hospitalization cost were analyzed. RESULTS: People between the ages of 16 and 55 were the most likely to suffer RTIs. The floating migrant patients between the ages of 16 and 45 had a higher incidence of accidents, while local resident patients between 46 and 55 had a higher incidence of accidents. Compared to local resident patients, floating migrant patients were more vulnerable to open injuries and severe traffic injuries. With the severity of injuries ranked from mild to severe, floating migrant patients had lower duration of inpatient stay, but higher hospitalization costs compared to local resident patients. CONCLUSIONS: Floating migrant patients had a different age distribution, severity of injuries, diseases, inpatient duration and hospitalization cost compared with local resident patients. Compared to local resident patients, floating migrants had a higher risk to RTIs and were more vulnerable to severer traffic accidents at lower ages.",2014 Jan 27,"['Xu, Chungui', 'Wang, Yanhua', 'Han, Na', 'Kou, Yuhui', 'Yin, Xiaofeng', 'Zhang, Peixun', 'Wang, Tianbing', 'Zhang, Dianying', 'Jiang, Baoguo']",PLoS One,,,True
d876d3d89d579f47df9ac251a4139ab1051561f5,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,True
7c4692c36869c3dfbd3507e70bdd74c11a0abec4,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
259ccfb33a20277e36150d6aad3ad88052123d15,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
31a504112c9e2d723989d5dbc83b2d14268b5d00,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
d332e54ea99c5fb3db1c18e6a4625aa7ace6ef31,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
392acb54f5179e12c68b78659be5d45df986707b,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
699bd0d52187342c078470d7d3d52f2046557830,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
2744c8c3be800ae8061c5cceb36d06d5d426b8a0,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
6624feb71eb178c0bf6ad26181e82432e634f991,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
f8feadd4392a7a0a031d1d0343f561ad9fd98370,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
470d07fc69e326fb26f10d21c103696232b021d2,PMC,Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk,http://dx.doi.org/10.1371/journal.pone.0086555,PMC3903544,24475142,CC BY,"During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations.",2014 Jan 27,"['Skowronski, Danuta M.', 'Hamelin, Marie-Eve', 'De Serres, Gaston', 'Janjua, Naveed Z.', 'Li, Guiyun', 'Sabaiduc, Suzana', 'Bouhy, Xavier', 'Couture, Christian', 'Leung, Anders', 'Kobasa, Darwyn', 'Embury-Hyatt, Carissa', 'de Bruin, Erwin', 'Balshaw, Robert', 'Lavigne, Sophie', 'Petric, Martin', 'Koopmans, Marion', 'Boivin, Guy']",PLoS One,,,False
5e77269850b7b4bf57514e226ea66cd48ac31db5,PMC,Profiling of Glycan Receptors for Minute Virus of Mice in Permissive Cell Lines Towards Understanding the Mechanism of Cell Recognition,http://dx.doi.org/10.1371/journal.pone.0086909,PMC3903596,24475195,CC BY,"The recognition of sialic acids by two strains of minute virus of mice (MVM), MVMp (prototype) and MVMi (immunosuppressive), is an essential requirement for successful infection. To understand the potential for recognition of different modifications of sialic acid by MVM, three types of capsids, virus-like particles, wild type empty (no DNA) capsids, and DNA packaged virions, were screened on a sialylated glycan microarray (SGM). Both viruses demonstrated a preference for binding to 9-O-methylated sialic acid derivatives, while MVMp showed additional binding to 9-O-acetylated and 9-O-lactoylated sialic acid derivatives, indicating recognition differences. The glycans recognized contained a type-2 Galβ1-4GlcNAc motif (Neu5Acα2-3Galβ1-4GlcNAc or 3′SIA-LN) and were biantennary complex-type N-glycans with the exception of one. To correlate the recognition of the 3′SIA-LN glycan motif as well as the biantennary structures to their natural expression in cell lines permissive for MVMp, MVMi, or both strains, the N- and O-glycans, and polar glycolipids present in three cell lines used for in vitro studies, A9 fibroblasts, EL4 T lymphocytes, and the SV40 transformed NB324K cells, were analyzed by MALDI-TOF/TOF mass spectrometry. The cells showed an abundance of the sialylated glycan motifs recognized by the viruses in the SGM and previous glycan microarrays supporting their role in cellular recognition by MVM. Significantly, the NB324K showed fucosylation at the non-reducing end of their biantennary glycans, suggesting that recognition of these cells is possibly mediated by the Lewis X motif as in 3′SIA-Le(X) identified in a previous glycan microarray screen.",2014 Jan 27,"['Halder, Sujata', 'Cotmore, Susan', 'Heimburg-Molinaro, Jamie', 'Smith, David F.', 'Cummings, Richard D.', 'Chen, Xi', 'Trollope, Alana J.', 'North, Simon J.', 'Haslam, Stuart M.', 'Dell, Anne', 'Tattersall, Peter', 'McKenna, Robert', 'Agbandje-McKenna, Mavis']",PLoS One,,,True
df1017e24101a51f6b5ca30ae2cb8376d8756a61,PMC,Dietary Enterococcus faecium NCIMB 10415 and Zinc Oxide Stimulate Immune Reactions to Trivalent Influenza Vaccination in Pigs but Do Not Affect Virological Response upon Challenge Infection,http://dx.doi.org/10.1371/journal.pone.0087007,PMC3904981,24489827,CC BY,"Swine influenza viruses (SIV) regularly cause significant disease in pigs worldwide. Since there is no causative treatment of SIV, we tested if probiotic Enterococcus (E.) faecium NCIMB 10415 or zinc (Zn) oxide as feed supplements provide beneficial effects upon SIV infection in piglets. Seventy-two weaned piglets were fed three different diets containing either E. faecium or different levels of Zn (2500 ppm, Zn(high); 50 ppm, Zn(low)). Half of the piglets were vaccinated intramuscularly (VAC) twice with an inactivated trivalent SIV vaccine, while all piglets were then infected intranasally with H3N2 SIV. Significantly higher weekly weight gains were observed in the E. faecium group before virus infection, and piglets in Zn(high) and E. faecium groups gained weight after infection while those in the control group (Zn(low)) lost weight. Using ELISA, we found significantly higher H3N2-specific antibody levels in the E. faecium+VAC group 2 days before and at the day of challenge infection as well as at 4 and 6 days after challenge infection. Higher hemagglutination inhibition (HI) titers were also observed in the Zn(high)+VAC and E. faecium+VAC groups at 0, 1 and 4 days after infection. However, there were no significant differences in virus shedding and lung lesions between the dietary groups. Using flow cytometry analysis significantly higher activated T helper cells and cytotoxic T lymphocyte percentages in the PBMCs were detected in the Zn(high) and E. faecium groups at single time points after infection compared to the Zn(low) control group, but no prolonged effect was found. In the BAL cells no influence of dietary supplementation on immune cell percentages could be detected. Our results suggest that feeding high doses of zinc oxide and particularly E. faecium could beneficially influence humoral immune responses after vaccination and recovery from SIV infection, but not affect virus shedding and lung pathology.",2014 Jan 28,"['Wang, Zhenya', 'Burwinkel, Michael', 'Chai, Weidong', 'Lange, Elke', 'Blohm, Ulrike', 'Breithaupt, Angele', 'Hoffmann, Bernd', 'Twardziok, Sven', 'Rieger, Juliane', 'Janczyk, Pawel', 'Pieper, Robert', 'Osterrieder, Nikolaus']",PLoS One,,,True
8ec3cfefcf560550c37dbc48107102bf2c893036,PMC,A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0087194,PMC3906132,24489870,CC BY,"The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.",2014 Jan 29,"['Dacheux, Laurent', 'Cervantes-Gonzalez, Minerva', 'Guigon, Ghislaine', 'Thiberge, Jean-Michel', 'Vandenbogaert, Mathias', 'Maufrais, Corinne', 'Caro, Valérie', 'Bourhy, Hervé']",PLoS One,,,True
33748091ef717d6cf46b0677a1d5592c48d7581e,PMC,A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0087194,PMC3906132,24489870,CC BY,"The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.",2014 Jan 29,"['Dacheux, Laurent', 'Cervantes-Gonzalez, Minerva', 'Guigon, Ghislaine', 'Thiberge, Jean-Michel', 'Vandenbogaert, Mathias', 'Maufrais, Corinne', 'Caro, Valérie', 'Bourhy, Hervé']",PLoS One,,,False
3114faaa4d11f6f05bd4702280615e2f8b44f488,PMC,A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0087194,PMC3906132,24489870,CC BY,"The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.",2014 Jan 29,"['Dacheux, Laurent', 'Cervantes-Gonzalez, Minerva', 'Guigon, Ghislaine', 'Thiberge, Jean-Michel', 'Vandenbogaert, Mathias', 'Maufrais, Corinne', 'Caro, Valérie', 'Bourhy, Hervé']",PLoS One,,,False
e07b6453dffb63c7ca686ce8e5772422f987d3e5,PMC,A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0087194,PMC3906132,24489870,CC BY,"The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.",2014 Jan 29,"['Dacheux, Laurent', 'Cervantes-Gonzalez, Minerva', 'Guigon, Ghislaine', 'Thiberge, Jean-Michel', 'Vandenbogaert, Mathias', 'Maufrais, Corinne', 'Caro, Valérie', 'Bourhy, Hervé']",PLoS One,,,False
da9beea6cc4a217fb31b54caf455ca229bf8a27b,PMC,A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0087194,PMC3906132,24489870,CC BY,"The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.",2014 Jan 29,"['Dacheux, Laurent', 'Cervantes-Gonzalez, Minerva', 'Guigon, Ghislaine', 'Thiberge, Jean-Michel', 'Vandenbogaert, Mathias', 'Maufrais, Corinne', 'Caro, Valérie', 'Bourhy, Hervé']",PLoS One,,,False
57935bbfea5e9eb4e25ef185f059ebb4362714d8,PMC,A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0087194,PMC3906132,24489870,CC BY,"The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.",2014 Jan 29,"['Dacheux, Laurent', 'Cervantes-Gonzalez, Minerva', 'Guigon, Ghislaine', 'Thiberge, Jean-Michel', 'Vandenbogaert, Mathias', 'Maufrais, Corinne', 'Caro, Valérie', 'Bourhy, Hervé']",PLoS One,,,False
af28c7f2e54f09c2ee5ea579d8646768a3be25c6,PMC,A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses,http://dx.doi.org/10.1371/journal.pone.0087194,PMC3906132,24489870,CC BY,"The prediction of viral zoonosis epidemics has become a major public health issue. A profound understanding of the viral population in key animal species acting as reservoirs represents an important step towards this goal. Bats harbor diverse viruses, some of which are of particular interest because they cause severe human diseases. However, little is known about the diversity of the global population of viruses found in bats (virome). We determined the viral diversity of five different French insectivorous bat species (nine specimens in total) in close contact with humans. Sequence-independent amplification, high-throughput sequencing with Illumina technology and a dedicated bioinformatics analysis pipeline were used on pooled tissues (brain, liver and lungs). Comparisons of the sequences of contigs and unassembled reads provided a global taxonomic distribution of virus-related sequences for each sample, highlighting differences both within and between bat species. Many viral families were present in these viromes, including viruses known to infect bacteria, plants/fungi, insects or vertebrates, the most relevant being those infecting mammals (Retroviridae, Herpesviridae, Bunyaviridae, Poxviridae, Flaviviridae, Reoviridae, Bornaviridae, Picobirnaviridae). In particular, we detected several new mammalian viruses, including rotaviruses, gammaretroviruses, bornaviruses and bunyaviruses with the identification of the first bat nairovirus. These observations demonstrate that bats naturally harbor viruses from many different families, most of which infect mammals. They may therefore constitute a major reservoir of viral diversity that should be analyzed carefully, to determine the role played by bats in the spread of zoonotic viral infections.",2014 Jan 29,"['Dacheux, Laurent', 'Cervantes-Gonzalez, Minerva', 'Guigon, Ghislaine', 'Thiberge, Jean-Michel', 'Vandenbogaert, Mathias', 'Maufrais, Corinne', 'Caro, Valérie', 'Bourhy, Hervé']",PLoS One,,,True
a04371951c94976a9b879f321764eb6dbeb4a9ab,PMC,Effect of Glycyrrhizin on Pseudomonal Skin Infections in Human-Mouse Chimeras,http://dx.doi.org/10.1371/journal.pone.0083747,PMC3907411,24497916,CC BY,"In our previous studies, peripheral blood lineage(−)CD34(+)CD31(+) cells (CD31(+) IMC) appearing in severely burned patients have been characterized as inhibitor cells for the production of β-defensins (HBDs) by human epidermal keratinocytes (NHEK). In this study, the effect of glycyrrhizin on pseudomonal skin infections was studied in a chimera model of thermal injury. Two different chimera models were utilized. Patient chimeras were created in murine antimicrobial peptide-depleted NOD-SCID IL-2rγ(null) mice that were grafted with unburned skin tissues of severely burned patients and inoculated with the same patient peripheral blood CD31(+) IMC. Patient chimera substitutes were created in the same mice that were grafted with NHEK and inoculated with experimentally induced CD31(+) IMC. In the results, both groups of chimeras treated with glycyrrhizin resisted a 20 LD(50) dose of P. aeruginosa skin infection, while all chimeras in both groups treated with saline died within 3 days of the infection. Human antimicrobial peptides were detected from the grafted site tissues of both groups of chimeras treated with glycyrrhizin, while the peptides were not detected in the same area tissues of controls. HBD-1 was produced by keratinocytes in transwell-cultures performed with CD31(+) IMC and glycyrrhizin. Also, inhibitors (IL-10 and CCL2) of HBD-1 production by keratinocytes were not detected in cultures of patient CD31(+) IMC treated with glycyrrhizin. These results indicate that sepsis stemming from pseudomonal grafted site infections in a chimera model of burn injury is controllable by glycyrrhizin. Impaired antimicrobial peptide production at the infection site of severely burned patients may be restored after treatment with glycyrrhizin.",2014 Jan 30,"['Yoshida, Shohei', 'Lee, Jong O.', 'Nakamura, Kiwamu', 'Suzuki, Sumihiro', 'Hendon, David N.', 'Kobayashi, Makiko', 'Suzuki, Fujio']",PLoS One,,,True
66d172659a7156097bd453af7028c06632c231a5,PMC,Cross sectional survey of human-bat interaction in Australia: public health implications,http://dx.doi.org/10.1186/1471-2458-14-58,PMC3908316,24443960,CC BY,"BACKGROUND: Flying foxes (megachiroptera) and insectivorous microbats (microchiroptera) are the known reservoirs for a range of recently emerged, highly pathogenic viruses. In Australia there is public health concern relating to bats’ role as reservoirs of Australian Bat Lyssavirus (ABLV), which has clinical features identical to classical rabies. Three deaths from ABLV have occurred in Australia. A survey was conducted to determine the frequency of bat exposures amongst adults in Australia’s most populous state, New South Wales; explore reasons for handling bats; examine reported practices upon encountering injured or trapped bats or experiencing bat bites or scratches; and investigate knowledge of bat handling warnings. METHODS: A representative sample of 821 New South Wales adults aged 16 years and older were interviewed during May and June 2011, using a computer assisted telephone interview (CATI) method. Frequencies, proportions and statistical differences in proportion were performed. Using an α-value of 0.05 and power of 80%, it was calculated that a sample size of 800 was required to provide statistical significance of +/− 5% for dichotomous variables. RESULTS: One-hundred-and-twenty-seven (15.5%) respondents indicated that they had previously handled a bat, being 22% (48/218) rural and 13% (78/597) urban respondents (χ(2) = 9.8, p = 0.0018). Twenty one percent of males (63/304) had handled bats compared with 12% (64/517) of females (χ(2) = 10.2, p = 0.0014). Overall, 42.0% (n = 345) of respondents reported having seen or heard a warning about handling bats. If faced with an injured or trapped bat, 25% (206/821) indicated that they would handle the bat, with 17% (36/206) saying that they would use their bare hands. For minor scratches, 14% (117/821) indicated that they would ignore the injury while four respondents would ignore major scratches or bites. CONCLUSIONS: Previous human-bat interactions were relatively common. Bat exposures most frequently occurred with sick or injured bats, which have the highest risk of ABLV. On encountering an injured or sick bat, potentially high risk practices were commonly reported, particularly among rural males. It is important to understand why people still handle bats despite public health warnings to inform future communication strategies.",2014 Jan 21,"['Paterson, Beverley J', 'Butler, Michelle T', 'Eastwood, Keith', 'Cashman, Patrick M', 'Jones, Alison', 'Durrheim, David N']",BMC Public Health,,,True
8589358e390499b6c9d95a5eb20b0bfb4bc75466,PMC,Idiopathic acute myocarditis during treatment for controlled human malaria infection: a case report,http://dx.doi.org/10.1186/1475-2875-13-38,PMC3909449,24479524,CC BY,"A 23-year-old healthy male volunteer took part in a clinical trial in which the volunteer took chloroquine chemoprophylaxis and received three intradermal doses at four-week intervals of aseptic, purified Plasmodium falciparum sporozoites to induce protective immunity against malaria. Fifty-nine days after the last administration of sporozoites and 32 days after the last dose of chloroquine the volunteer underwent controlled human malaria infection (CHMI) by the bites of five P. falciparum-infected mosquitoes. Eleven days post-CHMI a thick blood smear was positive (6 P. falciparum/μL blood) and treatment was initiated with atovaquone/proguanil (Malarone®). On the second day of treatment, day 12 post-CHMI, troponin T, a marker for cardiac tissue damage, began to rise above normal, and reached a maximum of 1,115 ng/L (upper range of normal = 14 ng/L) on day 16 post-CHMI. The volunteer had one ~20 minute episode of retrosternal chest pain and heavy feeling in his left arm on day 14 post-CHMI. ECG at the time revealed minor repolarization disturbances, and cardiac MRI demonstrated focal areas of subepicardial and midwall delayed enhancement of the left ventricle with some oedema and hypokinesia. A diagnosis of myocarditis was made. Troponin T levels were normal within 16 days and the volunteer recovered without clinical sequelae. Follow-up cardiac MRI at almost five months showed normal function of both ventricles and disappearance of oedema. Delayed enhancement of subepicardial and midwall regions decreased, but was still present. With the exception of a throat swab that was positive for rhinovirus on day 14 post-CHMI, no other tests for potential aetiologies of the myocarditis were positive. A number of possible aetiological factors may explain or have contributed to this case of myocarditis including, i) P. falciparum infection, ii) rhinovirus infection, iii) unidentified pathogens, iv) hyper-immunization (the volunteer received six travel vaccines between the last immunization and the CHMI), v) atovaquone/proguanil treatment, or vi) a combination of these factors. Definitive aetiology and pathophysiological mechanism for the myocarditis have not been established.",2014 Jan 30,"['van Meer, Maurits PA', 'Bastiaens, Guido JH', 'Boulaksil, Mohamed', 'de Mast, Quirijn', 'Gunasekera, Anusha', 'Hoffman, Stephen L', 'Pop, Gheorghe', 'van der Ven, André JAM', 'Sauerwein, Robert W']",Malar J,,,True
7115c4bf2dfc029be764f0cd2e13de0bf8ec1312,PMC,Long-Distance Travel Behaviours Accelerate and Aggravate the Large-Scale Spatial Spreading of Infectious Diseases,http://dx.doi.org/10.1155/2014/295028,PMC3910471,24511324,CC BY,"The study analyses the role of long-distance travel behaviours on the large-scale spatial spreading of directly transmitted infectious diseases, focusing on two different travel types in terms of the travellers travelling to a specific group or not. For this purpose, we have formulated and analysed a metapopulation model in which the individuals in each subpopulation are organised into a scale-free contact network. The long-distance travellers between the subpopulations will temporarily change the network structure of the destination subpopulation through the “merging effects (MEs),” which indicates that the travellers will be regarded as either connected components or isolated nodes in the contact network. The results show that the presence of the MEs has constantly accelerated the transmission of the diseases and aggravated the outbreaks compared to the scenario in which the diversity of the long-distance travel types is arbitrarily discarded. Sensitivity analyses show that these results are relatively constant regarding a wide range variation of several model parameters. Our study has highlighted several important causes which could significantly affect the spatiotemporal disease dynamics neglected by the present studies.",2014 Jan 8,"['Xu, Zhijing', 'Zu, Zhenghu', 'Zheng, Tao', 'Zhang, Wendou', 'Xu, Qing', 'Liu, Jinjie']",Comput Math Methods Med,,,True
7261e8caea6deec22cee8f20ba55074a99b11e60,PMC,Powerful Sequence Similarity Search Methods and In-Depth Manual Analyses Can Identify Remote Homologs in Many Apparently “Orphan” Viral Proteins,http://dx.doi.org/10.1128/JVI.02595-13,PMC3911697,24155369,CC BY,"The genome sequences of new viruses often contain many “orphan” or “taxon-specific” proteins apparently lacking homologs. However, because viral proteins evolve very fast, commonly used sequence similarity detection methods such as BLAST may overlook homologs. We analyzed a data set of proteins from RNA viruses characterized as “genus specific” by BLAST. More powerful methods developed recently, such as HHblits or HHpred (available through web-based, user-friendly interfaces), could detect distant homologs of a quarter of these proteins, suggesting that these methods should be used to annotate viral genomes. In-depth manual analyses of a subset of the remaining sequences, guided by contextual information such as taxonomy, gene order, or domain cooccurrence, identified distant homologs of another third. Thus, a combination of powerful automated methods and manual analyses can uncover distant homologs of many proteins thought to be orphans. We expect these methodological results to be also applicable to cellular organisms, since they generally evolve much more slowly than RNA viruses. As an application, we reanalyzed the genome of a bee pathogen, Chronic bee paralysis virus (CBPV). We could identify homologs of most of its proteins thought to be orphans; in each case, identifying homologs provided functional clues. We discovered that CBPV encodes a domain homologous to the Alphavirus methyltransferase-guanylyltransferase; a putative membrane protein, SP24, with homologs in unrelated insect viruses and insect-transmitted plant viruses having different morphologies (cileviruses, higreviruses, blunerviruses, negeviruses); and a putative virion glycoprotein, ORF2, also found in negeviruses. SP24 and ORF2 are probably major structural components of the virions.",2014 Jan,"['Kuchibhatla, Durga B.', 'Sherman, Westley A.', 'Chung, Betty Y. W.', 'Cook, Shelley', 'Schneider, Georg', 'Eisenhaber, Birgit', 'Karlin, David G.']",J Virol,,,False
db62bc4bb76fa5755a43e79b6da62374886f2439,PMC,Powerful Sequence Similarity Search Methods and In-Depth Manual Analyses Can Identify Remote Homologs in Many Apparently “Orphan” Viral Proteins,http://dx.doi.org/10.1128/JVI.02595-13,PMC3911697,24155369,CC BY,"The genome sequences of new viruses often contain many “orphan” or “taxon-specific” proteins apparently lacking homologs. However, because viral proteins evolve very fast, commonly used sequence similarity detection methods such as BLAST may overlook homologs. We analyzed a data set of proteins from RNA viruses characterized as “genus specific” by BLAST. More powerful methods developed recently, such as HHblits or HHpred (available through web-based, user-friendly interfaces), could detect distant homologs of a quarter of these proteins, suggesting that these methods should be used to annotate viral genomes. In-depth manual analyses of a subset of the remaining sequences, guided by contextual information such as taxonomy, gene order, or domain cooccurrence, identified distant homologs of another third. Thus, a combination of powerful automated methods and manual analyses can uncover distant homologs of many proteins thought to be orphans. We expect these methodological results to be also applicable to cellular organisms, since they generally evolve much more slowly than RNA viruses. As an application, we reanalyzed the genome of a bee pathogen, Chronic bee paralysis virus (CBPV). We could identify homologs of most of its proteins thought to be orphans; in each case, identifying homologs provided functional clues. We discovered that CBPV encodes a domain homologous to the Alphavirus methyltransferase-guanylyltransferase; a putative membrane protein, SP24, with homologs in unrelated insect viruses and insect-transmitted plant viruses having different morphologies (cileviruses, higreviruses, blunerviruses, negeviruses); and a putative virion glycoprotein, ORF2, also found in negeviruses. SP24 and ORF2 are probably major structural components of the virions.",2014 Jan,"['Kuchibhatla, Durga B.', 'Sherman, Westley A.', 'Chung, Betty Y. W.', 'Cook, Shelley', 'Schneider, Georg', 'Eisenhaber, Birgit', 'Karlin, David G.']",J Virol,,,True
a5243628f77d40d5861c26212a3cc3102d9b2449,PMC,"Clinical Epidemiology of Bocavirus, Rhinovirus, Two Polyomaviruses and Four Coronaviruses in HIV-Infected and HIV-Uninfected South African Children",http://dx.doi.org/10.1371/journal.pone.0086448,PMC3911925,24498274,CC BY,"BACKGROUND: Advances in molecular diagnostics have implicated newly-discovered respiratory viruses in the pathogenesis of pneumonia. We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV), human rhinovirus (hRV), polyomavirus-WU (WUPyV) and –KI (KIPyV) and human coronaviruses (CoV)-OC43, -NL63, -HKU1 and -229E among children hospitalized with lower respiratory tract infections (LRTI). METHODS: Multiplex real-time reverse-transcriptase polymerase chain reaction was undertaken on archived nasopharyngeal aspirates from HIV-infected and –uninfected children (<2 years age) hospitalized for LRTI, who had been previously investigated for respiratory syncytial virus, human metapneumovirus, parainfluenza I–III, adenovirus and influenza A/B. RESULTS: At least one of these viruses were identified in 274 (53.0%) of 517 and in 509 (54.0%) of 943 LRTI-episodes in HIV-infected and -uninfected children, respectively. Human rhinovirus was the most prevalent in HIV-infected (31.7%) and –uninfected children (32.0%), followed by CoV-OC43 (12.2%) and hBoV (9.5%) in HIV-infected; and by hBoV (13.3%) and WUPyV (11.9%) in HIV-uninfected children. Polyomavirus-KI (8.9% vs. 4.8%; p = 0.002) and CoV-OC43 (12.2% vs. 3.6%; p<0.001) were more prevalent in HIV-infected than –uninfected children. Combined with previously-tested viruses, respiratory viruses were identified in 60.9% of HIV-infected and 78.3% of HIV-uninfected children. The newly tested viruses were detected at high frequency in association with other respiratory viruses, including previously-investigated viruses (22.8% in HIV-infected and 28.5% in HIV–uninfected children). CONCLUSIONS: We established that combined with previously-investigated viruses, at least one respiratory virus was identified in the majority of HIV-infected and HIV-uninfected children hospitalized for LRTI. The high frequency of viral co-infections illustrates the complexities in attributing causality to specific viruses in the aetiology of LRTI and may indicate a synergetic role of viral co-infections in the pathogenesis of childhood LRTI.",2014 Feb 3,"['Nunes, Marta C.', 'Kuschner, Zachary', 'Rabede, Zelda', 'Madimabe, Richard', 'Van Niekerk, Nadia', 'Moloi, Jackie', 'Kuwanda, Locadiah', 'Rossen, John W.', 'Klugman, Keith P.', 'Adrian, Peter V.', 'Madhi, Shabir A.']",PLoS One,,,True
347209baac4ddbcc1533979d1a496128d7834f5e,PMC,Public knowledge and preventive behavior during a large-scale Salmonella outbreak: results from an online survey in the Netherlands,http://dx.doi.org/10.1186/1471-2458-14-100,PMC3913330,24479614,CC BY,"BACKGROUND: Food-borne Salmonella infections are a worldwide concern. During a large-scale outbreak, it is important that the public follows preventive advice. To increase compliance, insight in how the public gathers its knowledge and which factors determine whether or not an individual complies with preventive advice is crucial. METHODS: In 2012, contaminated salmon caused a large Salmonella Thompson outbreak in the Netherlands. During the outbreak, we conducted an online survey (n = 1,057) to assess the general public’s perceptions, knowledge, preventive behavior and sources of information. RESULTS: Respondents perceived Salmonella infections and the 2012 outbreak as severe (m = 4.21; five-point scale with 5 as severe). Their knowledge regarding common food sources, the incubation period and regular treatment of Salmonella (gastro-enteritis) was relatively low (e.g., only 28.7% knew that Salmonella is not normally treated with antibiotics). Preventive behavior differed widely, and the majority (64.7%) did not check for contaminated salmon at home. Most information about the outbreak was gathered through traditional media and news and newspaper websites. This was mostly determined by time spent on the medium. Social media played a marginal role. Wikipedia seemed a potentially important source of information. CONCLUSIONS: To persuade the public to take preventive actions, public health organizations should deliver their message primarily through mass media. Wikipedia seems a promising instrument for educating the public about food-borne Salmonella.",2014 Jan 31,"['van Velsen, Lex', 'Beaujean, Desirée JMA', 'van Gemert-Pijnen, Julia EWC', 'van Steenbergen, Jim E', 'Timen, Aura']",BMC Public Health,,,True
784c237bbdda9fbc087e1f42ce10e4948aa34a1b,PMC,Novel Bifunctional Single-Chain Variable Antibody Fragments to Enhance Virolysis by Complement: Generation and Proof-of-Concept,http://dx.doi.org/10.1155/2014/971345,PMC3913500,24524088,CC BY,"When bound to the envelope of viruses, factor H (FH), a soluble regulator of complement activation, contributes to the protection against a potent immune defense mechanism, the complement-mediated lysis (CML). Thus, removing FH from the surface renders viruses, such as HIV, susceptible to CML. For a proof of concept, we developed a construct consisting of recombinant bifunctional single-chain variable fragment (scFv) based on a monoclonal antibody against Friend murine leukemia virus (F-MuLV) envelope protein gp70, which was coupled to specific binding domains (short consensus repeats 19-20; SCR1920) of FH. We used Pichia pastoris as expression system in common shake flasks and optimized expression in high density bench top fermentation. Specific binding of recombinant scFv was proven by flow cytometry. The recombinant scFv-SCR significantly enhanced CML of F-MuLV in vitro implying that FH binding to the viral surface was impaired by the scFv-SCR. This novel concept to enhance virolysis may provide a new approach for antiviral treatment.",2014 Jan 12,"['Huber, Georg', 'Bánki, Zoltán', 'Kunert, Renate', 'Stoiber, Heribert']",Biomed Res Int,,,False
52431fafe4d5ccd27011d899aa54aa5aa3537e95,PMC,Novel Bifunctional Single-Chain Variable Antibody Fragments to Enhance Virolysis by Complement: Generation and Proof-of-Concept,http://dx.doi.org/10.1155/2014/971345,PMC3913500,24524088,CC BY,"When bound to the envelope of viruses, factor H (FH), a soluble regulator of complement activation, contributes to the protection against a potent immune defense mechanism, the complement-mediated lysis (CML). Thus, removing FH from the surface renders viruses, such as HIV, susceptible to CML. For a proof of concept, we developed a construct consisting of recombinant bifunctional single-chain variable fragment (scFv) based on a monoclonal antibody against Friend murine leukemia virus (F-MuLV) envelope protein gp70, which was coupled to specific binding domains (short consensus repeats 19-20; SCR1920) of FH. We used Pichia pastoris as expression system in common shake flasks and optimized expression in high density bench top fermentation. Specific binding of recombinant scFv was proven by flow cytometry. The recombinant scFv-SCR significantly enhanced CML of F-MuLV in vitro implying that FH binding to the viral surface was impaired by the scFv-SCR. This novel concept to enhance virolysis may provide a new approach for antiviral treatment.",2014 Jan 12,"['Huber, Georg', 'Bánki, Zoltán', 'Kunert, Renate', 'Stoiber, Heribert']",Biomed Res Int,,,True
8ecf2ad1996b1e93edd3eb7a8b2207114a33818a,PMC,Epidemiology of Multi-Drug Resistant Organisms in a Teaching Hospital in Oman: A One-Year Hospital-Based Study,http://dx.doi.org/10.1155/2014/157102,PMC3914445,24526881,CC BY,"Background. Antimicrobial resistance is increasingly recognized as a global challenge. A few studies have emerged on epidemiology of multidrug resistant organisms in tertiary care settings in the Arabian Gulf. Aim. To describe the epidemiology of multi-drug resistant organisms (MDRO) at Sultan Qaboos University Hospital, a tertiary hospital in Oman. Methods. A retrospective review of MDRO records has been conducted throughout the period from January 2012 till December 2012. Organisms were identified and tested by an automated identification and susceptibility system, and the antibiotic susceptibility testing was confirmed by the disk diffusion method. Results. Out of the total of 29,245 admissions, there have been 315 patients registered as MDRO patients giving an overall prevalence rate of 10.8 (95% CI 9.3, 12.4) MDRO cases per 1000 admissions. In addition, the prevalence rate of MDRO isolates was 11.2 (95% CI 9.7, 12.9) per 1000 admissions. Overall, increasing trends in prevalence rates of MDRO patients and MDRO isolates were observed throughout the study period. Conclusion. Antimicrobial resistance is an emerging challenge in Oman. Continuous monitoring of antimicrobial susceptibility and strict adherence to infection prevention guidelines are essential to prevent proliferation of MDRO. Along such quest, stringent antibiotic prescription guidelines are needed in the country.",2014 Jan 14,"['Balkhair, Abdullah', 'Al-Farsi, Yahya M.', 'Al-Muharrmi, Zakariya', 'Al-Rashdi, Raiya', 'Al-Jabri, Mansoor', 'Neilson, Fatma', 'Al-Adawi, Sara S.', 'El-Beeli, Marah', 'Al-Adawi, Samir']",ScientificWorldJournal,,,True
107824986103d1409f047ec9823d75b7b25d9702,PMC,Effect of the One-Child Policy on Influenza Transmission in China: A Stochastic Transmission Model,http://dx.doi.org/10.1371/journal.pone.0084961,PMC3916292,24516519,CC BY,"BACKGROUND: China's one-child-per-couple policy, introduced in 1979, led to profound demographic changes for nearly a quarter of the world's population. Several decades later, the consequences include decreased fertility rates, population aging, decreased household sizes, changes in family structure, and imbalanced sex ratios. The epidemiology of communicable diseases may have been affected by these changes since the transmission dynamics of infectious diseases depend on demographic characteristics of the population. Of particular interest is influenza because China and Southeast Asia lie at the center of a global transmission network of influenza. Moreover, changes in household structure may affect influenza transmission. Is it possible that the pronounced demographic changes that have occurred in China have affected influenza transmission? METHODS AND FINDINGS: To address this question, we developed a continuous-time, stochastic, individual-based simulation model for influenza transmission. With this model, we simulated 30 years of influenza transmission and compared influenza transmission rates in populations with and without the one-child policy control. We found that the average annual attack rate is reduced by 6.08% (SD 2.21%) in the presence of the one-child policy compared to a population in which no demographic changes occurred. There was no discernible difference in the secondary attack rate, −0.15% (SD 1.85%), between the populations with and without a one-child policy. We also forecasted influenza transmission over a ten-year time period in a population with a two-child policy under a hypothesis that a two-child-per-couple policy will be carried out in 2015, and found a negligible difference in the average annual attack rate compared to the population with the one-child policy. CONCLUSIONS: This study found that the average annual attack rate is slightly lowered in a population with a one-child policy, which may have resulted from a decrease in household size and the proportion of children in the population.",2014 Feb 6,"['Liu, Fengchen', 'Enanoria, Wayne T. A.', 'Ray, Kathryn J.', 'Coffee, Megan P.', 'Gordon, Aubree', 'Aragón, Tomás J.', 'Yu, Guowei', 'Cowling, Benjamin J.', 'Porco, Travis C.']",PLoS One,,,True
992365f92b227163487b5b2aa46063f842e7b36e,PMC,ABSL-4 Aerobiology Biosafety and Technology at the NIH/NIAID Integrated Research Facility at Fort Detrick,http://dx.doi.org/10.3390/v6010137,PMC3917435,24402304,CC BY,"The overall threat of a viral pathogen to human populations is largely determined by the modus operandi and velocity of the pathogen that is transmitted among humans. Microorganisms that can spread by aerosol are considered a more challenging enemy than those that require direct body-to-body contact for transmission, due to the potential for infection of numerous people rather than a single individual. Additionally, disease containment is much more difficult to achieve for aerosolized viral pathogens than for pathogens that spread solely via direct person-to-person contact. Thus, aerobiology has become an increasingly necessary component for studying viral pathogens that are naturally or intentionally transmitted by aerosol. The goal of studying aerosol viral pathogens is to improve public health preparedness and medical countermeasure development. Here, we provide a brief overview of the animal biosafety level 4 Aerobiology Core at the NIH/NIAID Integrated Research Facility at Fort Detrick, Maryland, USA.",2014 Jan 7,"['Lackemeyer, Matthew G.', 'de Kok-Mercado, Fabian', 'Wada, Jiro', 'Bollinger, Laura', 'Kindrachuk, Jason', 'Wahl-Jensen, Victoria', 'Kuhn, Jens H.', 'Jahrling, Peter B.']",Viruses,,,True
e8679d8c149ea6d25afb92e8a4f4b622dadcd872,PMC,Alveolar Macrophages Infected with Ames or Sterne Strain of Bacillus anthracis Elicit Differential Molecular Expression Patterns,http://dx.doi.org/10.1371/journal.pone.0087201,PMC3917846,24516547,CC0,"Alveolar macrophages (AMs) phagocytose Bacillus anthracis following inhalation and induce the production of pro-inflammatory cytokines and chemokines to mediate the activation of innate immunity. Ames, the virulent strain of B. anthracis, contains two plasmids that encode the antiphagocytic poly-γ-d-glutamic acid capsule and the lethal toxin. The attenuated Sterne strain of B. anthracis, which lacks the plasmid encoding capsule, is widely adapted as a vaccine strain. Although differences in the outcome of infection with the two strains may have originated from the presence or absence of an anti-phagocytic capsule, the disease pathogenesis following infection will be manifested via the host responses, which is not well understood. To gain understanding of the host responses at cellular level, a microarray analysis was performed using primary rhesus macaque AMs infected with either Ames or Sterne spores. Notably, 528 human orthologs were identified to be differentially expressed in AMs infected with either strain of the B. anthracis. Meta-analyses revealed genes differentially expressed in response to B. anthracis infection were also induced upon infections with multiple pathogens such as Francisella Novicida or Staphylococcus aureus. This suggests the existence of a common molecular signature in response to pathogen infections. Importantly, the microarray and protein expression data for certain cytokines, chemokines and host factors provide further insights on how cellular processes such as innate immune sensing pathways, anti-apoptosis versus apoptosis may be differentially modulated in response to the virulent or vaccine strain of B. anthracis. The reported differences may account for the marked difference in pathogenicity between these two strains.",2014 Feb 7,"['Langel, Felicia D.', 'Chiang, Chih-Yuan', 'Lane, Douglas', 'Kenny, Tara', 'Ojeda, Jenifer F.', 'Zhong, Yang', 'Che, Jianwei', 'Zhou, Yingyao', 'Ribot, Wilson', 'Kota, Krishna P.', 'Bavari, Sina', 'Panchal, Rekha G.']",PLoS One,,,True
b0da552a101206a82845a47dc3ee9f0a64ed2bac,PMC,"Respiratory viruses within homeless shelters in Marseille, France",http://dx.doi.org/10.1186/1756-0500-7-81,PMC3918144,24499605,CC BY,"BACKGROUND: Homeless shelters are identified as places where humans are at high risk of acquiring respiratory disease. We previously reported the prevalence of the main respiratory diseases affecting a population of homeless in Marseille, France. Here, we investigated the prevalence of 10 respiratory viruses in a similar homeless population during 2 successive winter seasons. FINDINGS: Following a clinical examination, we collected nasal specimens from which the RT-PCR detection of 10 respiratory viruses was performed through snapshot investigations. Among the 265 patients included, 150 (56.6%) reported at least one respiratory symptom of which 13 (8.7%) had positive swabs for at least one respiratory virus, and 115 patients reported any respiratory symptom of which 10 (8.7%) had positive swabs for respiratory virus. Overall, 23 patients had positive swabs for at least one respiratory virus. Human rhinovirus (HRV) was the predominant virus (13 isolates) followed by enteroviruses (3), human metapneumovirus (2), human coronavirus OC43 (2), 229E virus (2) and human respiratory syncytial virus subtype B (1). Among the patients infected with HRV, 10 were collected during the same snapshot. CONCLUSIONS: Although one half of the patients reported respiratory symptoms, the prevalence of respiratory viruses was within the range of that previously described in adult asymptomatic patients outside the homeless community. Most HRV-positive swabs were collected during the same snapshot suggesting a local outbreak. No influenza viruses were found despite the fact that one half of the patients were investigated during the peak of the seasonal influenza epidemic in Marseille.",2014 Feb 5,"['Thiberville, Simon-djamel', 'Salez, Nicolas', 'Benkouiten, Samir', 'Badiaga, Sekene', 'Charrel, Remi', 'Brouqui, Philippe']",BMC Res Notes,,,True
173ce92cbc6f228d5bfbdbd7ba7137523ebe36bd,PMC,Emergence of Enteric Viruses in Production Chickens Is a Concern for Avian Health,http://dx.doi.org/10.1155/2014/450423,PMC3919086,24578633,CC BY,"Several viruses have been identified in recent years in the intestinal contents of chickens and turkeys with enteric problems, which have been observed in commercial farms worldwide, including Brazil. Molecular detection of these viruses in Brazil can transform to a big threat for poultry production due to risk for intestinal integrity. This disease is characterized by severely delayed growth, low uniformity, lethargy, watery diarrhea, delayed feed consumption, and a decreased conversion rate. Chicken astrovirus (CAstV), rotavirus, reovirus, chicken parvovirus (ChPV), fowl adenovirus of subgroup I (FAdV-1), and avian nephritis virus (ANV) were investigated using the conventional polymerase chain reaction (PCR) and the reverse transcription polymerase chain reaction (RT-PCR). In addition, the infectious bronchitis virus (IBV), which may play a role in enteric disease, was included. The viruses most frequently detected, either alone or in concomitance with other viruses, were IBV, ANV, rotavirus, and CAstV followed by parvovirus, reovirus, and adenovirus. This study demonstrates the diversity of viruses in Brazilian chicken flocks presenting enteric problems characterized by diarrhea, growth retard, loss weight, and mortality, which reflects the multicausal etiology of this disease.",2014 Jan 22,"['Mettifogo, Elena', 'Nuñez, Luis F. N.', 'Chacón, Jorge L.', 'Santander Parra, Silvana H.', 'Astolfi-Ferreira, Claudete S.', 'Jerez, José A.', 'Jones, Richard C.', 'Piantino Ferreira, Antonio J.']",ScientificWorldJournal,,,True
1c5f2a7a584371461fa19a49e49c99ecd0ef7743,PMC,"Genetic Variability and Phylogeny of Current Chinese Porcine Epidemic Diarrhea Virus Strains Based on Spike, ORF3, and Membrane Genes",http://dx.doi.org/10.1155/2014/208439,PMC3919097,24578626,CC BY,"Since late 2010, the outbreak of porcine epidemic diarrhea (PED) in China has resulted in the deaths of millions of suckling piglets. The main cause of the disease outbreak was unknown. In this study, partial spike (S), ORF3, and membrane (M) genes amplified from these variants were sequenced and analyzed. The results showed that the variants could be clustered into one to three subgroups and suggested that S genes were variable, while M genes were relatively conserved. Moreover, in comparison with the vaccine strain CV777, sequence alignment analyses revealed that the S genes of the newly isolated strains contained several mutations at the aa level. It is possible that these mutations have changed the hydrophobicity of the S protein and influenced the viral antigenicity and virulence. Interestingly, homology analyses based on ORF3 demonstrated that the isolates had an intact opening reading frame (ORF), which were different from the attenuated DR13 strain. In conclusion, the widespread PED virus (PEDV) isolates had virulent characteristics. Additionally, the high degree of variation in the genes, particularly S genes, might provide an explanation for the poor immunity and rapid spread of the disease.",2014 Jan 22,"['Sun, Ruiqin', 'Leng, Zhangming', 'Zhai, Shao-Lun', 'Chen, Dekun', 'Song, Changxu']",ScientificWorldJournal,,,True
66daba9fe4360f00714bd778402b6ac3489b2ec6,PMC,Stimulation of ribosomal frameshifting by RNA G-quadruplex structures,http://dx.doi.org/10.1093/nar/gkt1022,PMC3919603,24178029,CC BY,"Guanine-rich sequences can fold into four-stranded structures of stacked guanine-tetrads, so-called G-quadruplexes (G4). These unique motifs have been extensively studied on the DNA level; however, exploration of the biological roles of G4s at the RNA level is just emerging. Here we show that G4 RNA when introduced within coding regions are capable of stimulating −1 ribosomal frameshifting (−1 FS) in vitro and in cultured cells. Systematic manipulation of the loop length between each G-tract revealed that the −1 FS efficiency positively correlates with G4 stability. Addition of a G4-stabilizing ligand, PhenDC3, resulted in higher −1 FS. Further, we demonstrated that the G4s can stimulate +1 FS and stop codon readthrough as well. These results suggest a potentially novel translational gene regulation mechanism mediated by G4 RNA.",2014 Feb 30,"['Yu, Chien-Hung', 'Teulade-Fichou, Marie-Paule', 'Olsthoorn, René C. L.']",Nucleic Acids Res,,,True
cada5b298ac838d0b1414918d4c0eba698ee7276,PMC,Stimulation of ribosomal frameshifting by RNA G-quadruplex structures,http://dx.doi.org/10.1093/nar/gkt1022,PMC3919603,24178029,CC BY,"Guanine-rich sequences can fold into four-stranded structures of stacked guanine-tetrads, so-called G-quadruplexes (G4). These unique motifs have been extensively studied on the DNA level; however, exploration of the biological roles of G4s at the RNA level is just emerging. Here we show that G4 RNA when introduced within coding regions are capable of stimulating −1 ribosomal frameshifting (−1 FS) in vitro and in cultured cells. Systematic manipulation of the loop length between each G-tract revealed that the −1 FS efficiency positively correlates with G4 stability. Addition of a G4-stabilizing ligand, PhenDC3, resulted in higher −1 FS. Further, we demonstrated that the G4s can stimulate +1 FS and stop codon readthrough as well. These results suggest a potentially novel translational gene regulation mechanism mediated by G4 RNA.",2014 Feb 30,"['Yu, Chien-Hung', 'Teulade-Fichou, Marie-Paule', 'Olsthoorn, René C. L.']",Nucleic Acids Res,,,False
3e01904917aea1c46193a3e98307e95be703c7c6,PMC,Cyclophilin A: a key player for human disease,http://dx.doi.org/10.1038/cddis.2013.410,PMC3920964,24176846,CC BY,"Cyclophilin A (CyPA) is a ubiquitously distributed protein belonging to the immunophilin family. CyPA has peptidyl prolyl cis-trans isomerase (PPIase) activity, which regulates protein folding and trafficking. Although CyPA was initially believed to function primarily as an intracellular protein, recent studies have revealed that it can be secreted by cells in response to inflammatory stimuli. Current research in animal models and humans has provided compelling evidences supporting the critical function of CyPA in several human diseases. This review discusses recently available data about CyPA in cardiovascular diseases, viral infections, neurodegeneration, cancer, rheumatoid arthritis, sepsis, asthma, periodontitis and aging. It is believed that further elucidations of the role of CyPA will provide a better understanding of the molecular mechanisms underlying these diseases and will help develop novel pharmacological therapies.",2013 Oct 31,"['Nigro, P', 'Pompilio, G', 'Capogrossi, M C']",Cell Death Dis,,,True
1c995ac4ae70bbcc5da53211e20df4398d1ce55d,PMC,"Autophagic response in the Rabbit Hemorrhagic Disease, an animal model of virally-induced fulminant hepatic failure",http://dx.doi.org/10.1186/1297-9716-45-15,PMC3922607,24490870,CC BY,"The Rabbit Hemorrhagic Disease Virus (RHDV) induces a severe disease that fulfils many requirements of an animal model of fulminant hepatic failure. However, a better knowledge of molecular mechanisms contributing to liver damage is required, and it is unknown whether the RHDV induces liver autophagy and how it relates to apoptosis. In this study, we attempted to explore which signalling pathways were involved in the autophagic response induced by the RHDV and to characterize their role in the context of RHDV pathogenesis. Rabbits were infected with 2 × 10(4) hemmaglutination units of a RHDV isolate. The autophagic response was measured as presence of autophagic vesicles, LC3 staining, conversion of LC3-I to autophagosome-associated LC3-II and changes in expression of beclin-1, UVRAG, Atg5, Atg12, Atg16L1 and p62/SQSTM1. RHDV-triggered autophagy reached a maximum at 24 hours post-infection (hpi) and declined at 30 and 36 hpi. Phosphorylation of mTOR also augmented in early periods of infection and there was an increase in the expression of the endoplasmic reticulum chaperones BiP/GRP78, CHOP and GRP94. Apoptosis, measured as caspase-3 activity and expression of PARP-1, increased significantly at 30 and 36 hpi in parallel to the maximal expression of the RHDV capsid protein VP60. These data indicate that RHDV infection initiates a rapid autophagic response, perhaps in an attempt to protect liver, which associates to ER stress development and is independent from downregulation of the major autophagy suppressor mTOR. As the infection continues and the autophagic response declines, cells begin to exhibit apoptosis.",2014 Feb 4,"['Vallejo, Daniela', 'Crespo, Irene', 'San-Miguel, Beatriz', 'Álvarez, Marcelino', 'Prieto, Jesús', 'Tuñón, María Jesús', 'González-Gallego, Javier']",Vet Res,,,True
58f9cce5d568b8cc7c7eb62a3b03b476a5ced52d,PMC,"Animal Viruses, Bacteria, and Cancer: A Brief Commentary",http://dx.doi.org/10.3389/fpubh.2014.00014,PMC3923154,24592380,CC BY,"Animal viruses and bacteria are ubiquitous in the environment. However, little is known about their mode of transmission and etiologic role in human cancers, especially among high-risk groups (e.g., farmers, veterinarians, poultry plant workers, pet owners, and infants). Many factors may affect the survival, transmissibility, and carcinogenicity of these agents, depending on the animal-host environment, hygiene practices, climate, travel, herd immunity, and cultural differences in food consumption and preparation. Seasonal variations in immune function also may increase host susceptibility at certain times of the year. The lack of objective measures, inconsistent study designs, and sources of epidemiologic bias (e.g., residual confounding, recall bias, and non-randomized patient selection) are some of the factors that complicate a clear understanding of this subject.",2014 Feb 13,"['Efird, Jimmy T.', 'Davies, Stephen W.', 'O’Neal, Wesley T.', 'Anderson, Ethan J.']",Front Public Health,,,True
074b685a347c109752be7efe757c3985190ec6c4,PMC,"Vaccine Effectiveness against Medically Attended Laboratory-Confirmed Influenza in Japan, 2011–2012 Season",http://dx.doi.org/10.1371/journal.pone.0088813,PMC3923823,24551167,CC BY,"The objective of this study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza during the 2011–2012 season in Japan using a test-negative case-control study design. The effect of co-circulating non-influenza respiratory viruses (NIRVs) on VE estimates was also explored. Nasopharyngeal swab samples were collected from outpatients with influenza-like illnesses (ILIs) in a community hospital in Nagasaki, Japan. Thirteen respiratory viruses (RVs), including influenza A and B, were identified from the samples using a multiplex polymerase chain reaction. The difference in VE point estimates was assessed using three different controls: ILI patients that tested negative for influenza, those that tested negative for all RVs, and those that tested positive for NIRVs. The adjusted VE against medically attended, laboratory-confirmed influenza using all influenza-negative controls was 5.3% (95% confidence interval [CI], −60.5 to 44.1). The adjusted VEs using RV-negative and NIRV-positive controls were −1.5% (95% CI, −74.7 to 41) and 50% (95% CI, −43.2 to 82.5), respectively. Influenza VE was limited in Japan during the 2011–2012 season. Although the evidence is not conclusive, co-circulating NIRVs may affect influenza VE estimates in test-negative case-control studies.",2014 Feb 13,"['Suzuki, Motoi', 'Minh, Le Nhat', 'Yoshimine, Hiroyuki', 'Inoue, Kenichiro', 'Yoshida, Lay Myint', 'Morimoto, Konosuke', 'Ariyoshi, Koya']",PLoS One,,,True
2000b147cb90354ba98206dffbc47deddddcc84d,PMC,Utilization of and Direct Expenditure for Emergency Medical
Care in Taiwan: A Population-based Descriptive Study,http://dx.doi.org/10.2188/jea.JE20080042,PMC3924095,19164870,CC BY,"BACKGROUND: We surveyed the emergency medical system (EMS) in Taiwan to provide information to policymakers responsible for decisions regarding the redistribution of national medical resources. METHODS: A systematic sampling method was used to randomly sample a representative database from the National Health Insurance (NHI) database in Taiwan, during the period from 2000 to 2004. RESULTS: We identified 10,124, 10,408, 11,209, 10,686, and 11,914 emergency room visits in 2000, 2001, 2002, 2003, and 2004, respectively. There were more males than females, and the majority of adults were younger than 50 years. Diagnose of injury/poisoning was the most frequently noted diagnostic category in emergency departments (EDs) in Taiwan. There were 13,196 (24.3%) and 2,952 (5.4%) patients with 2 and 3 concomitant diagnoses, respectively. There was a significant association between advanced age and the existence of multiple diagnoses (P < 0.001). With the exception of the ill-defined symptoms/signs/conditions, the two most frequent diagnoses were diseases of the circulatory system and diseases of the respiratory system in patients aged 65 years or older. On average, treatment-associated expenditure and drug-associated expenditure in Taiwan EDs averaged NT$1,155 ($35.0) and NT$190 ($5.8), respectively, which was equal to 64.5% and 10.6% of the total ED-associated cost. General ED medical expenditure increased with patient age; the increased cost ratio due to age was estimated at 8% per year (P < 0.001). CONCLUSIONS: The frequency of major health problems diagnosed at ED visits varied by age: more complicated complaints and multiple diagnoses were more frequent in older patients. In Taiwan, the ED system remains overloaded, possibly because of the low cost of an ED visit.",2009 Jan 30,"['Yang, Nan-Ping', 'Lee, Yi-Hui', 'Lin, Ching-Heng', 'Chung, Yuan-Chang', 'Chen, Wen-Jone', 'Chou, Pesus']",J Epidemiol,,,True
6ff529e1f29ef13037ef1117086082db53d12691,PMC,Support vector machine (SVM) based multiclass prediction with basic statistical analysis of plasminogen activators,http://dx.doi.org/10.1186/1756-0500-7-63,PMC3924408,24468032,CC BY,"BACKGROUND: Plasminogen (Pg), the precursor of the proteolytic and fibrinolytic enzyme of blood, is converted to the active enzyme plasmin (Pm) by different plasminogen activators (tissue plasminogen activators and urokinase), including the bacterial activators streptokinase and staphylokinase, which activate Pg to Pm and thus are used clinically for thrombolysis. The identification of Pg-activators is therefore an important step in understanding their functional mechanism and derives new therapies. METHODS: In this study, different computational methods for predicting plasminogen activator peptide sequences with high accuracy were investigated, including support vector machines (SVM) based on amino acid (AC), dipeptide composition (DC), PSSM profile and Hybrid methods used to predict different Pg-activators from both prokaryotic and eukaryotic origins. RESULTS: Overall maximum accuracy, evaluated using the five-fold cross validation technique, was 88.37%, 84.32%, 87.61%, 85.63% in 0.87, 0.83,0.86 and 0.85 MCC with amino (AC) or dipeptide composition (DC), PSSM profile and Hybrid methods respectively. Through this study, we have found that the different subfamilies of Pg-activators are quite closely correlated in terms of amino, dipeptide, PSSM and Hybrid compositions. Therefore, our prediction results show that plasminogen activators are predictable with a high accuracy from their primary sequence. Prediction performance was also cross-checked by confusion matrix and ROC (Receiver operating characteristics) analysis. A web server to facilitate the prediction of Pg-activators from primary sequence data was implemented. CONCLUSION: The results show that dipeptide, PSSM profile, and Hybrid based methods perform better than single amino acid composition (AC). Furthermore, we also have developed a web server, which predicts the Pg-activators and their classification (available online at http://mamsap.it.deakin.edu.au/plas_pred/home.html). Our experimental results show that our approaches are faster and achieve generally a good prediction performance.",2014 Jan 27,"['Muthukrishnan, Selvaraj', 'Puri, Munish', 'Lefevre, Christophe']",BMC Res Notes,,,True
1fdefb8aa4368ef11e32bad469c37591b0eb24bc,PMC,Recent developments in antiviral agents against enterovirus 71 infection,http://dx.doi.org/10.1186/1423-0127-21-14,PMC3924904,24521134,CC BY,"Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD). Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. The absence of licensed therapeutics for clinical use has intensified research into anti-EV-71 development. This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase. The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening. Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals. The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine. The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.",2014 Feb 12,"['Tan, Chee Wah', 'Lai, Jeffrey Kam Fatt', 'Sam, I-Ching', 'Chan, Yoke Fun']",J Biomed Sci,,,True
dc38fa3321df5137294140ffe1a358399befb500,PMC,Distinct Immune Response in Two MERS-CoV-Infected Patients: Can We Go from Bench to Bedside?,http://dx.doi.org/10.1371/journal.pone.0088716,PMC3925152,24551142,CC BY,"One year after the occurrence of the first case of infection by the Middle East Respiratory Syndrome coronavirus (MERS-CoV) there is no clear consensus on the best treatment to propose. The World Health Organization, as well as several other national agencies, are still working on different clinical approaches to implement the most relevant treatment in MERS-CoV infection. We compared innate and adaptive immune responses of two patients infected with MERS-CoV to understand the underlying mechanisms involved in the response and propose potential therapeutic approaches. Broncho-alveolar lavage (BAL) of the first week and sera of the first month from the two patients were used in this study. Quantitative polymerase chain reaction (qRTPCR) was performed after extraction of RNA from BAL cells of MERS-CoV infected patients and control patients. BAL supernatants and sera were used to assess cytokines and chemokines secretion by enzyme-linked immunosorbent assay. The first patient died rapidly after 3 weeks in the intensive care unit, the second patient still recovers from infection. The patient with a poor outcome (patient 1), compared to patient 2, did not promote type-1 Interferon (IFN), and particularly IFNα, in response to double stranded RNA (dsRNA) from MERS-CoV. The absence of IFNα, known to promote antigen presentation in response to viruses, impairs the development of a robust antiviral adaptive Th-1 immune response. This response is mediated by IL-12 and IFNγ that decreases viral clearance; levels of both of these mediators were decreased in patient 1. Finally, we confirm previous in vitro findings that MERS-CoV can drive IL-17 production in humans. Host recognition of viral dsRNA determines outcome in the early stage of MERS-CoV infection. We highlight the critical role of IFNα in this initial stage to orchestrate a robust immune response and bring substantial arguments for the indication of early IFNα treatment during MERS-CoV infection.",2014 Feb 14,"['Faure, Emmanuel', 'Poissy, Julien', 'Goffard, Anne', 'Fournier, Clement', 'Kipnis, Eric', 'Titecat, Marie', 'Bortolotti, Perinne', 'Martinez, Laura', 'Dubucquoi, Sylvain', 'Dessein, Rodrigue', 'Gosset, Philippe', 'Mathieu, Daniel', 'Guery, Benoit']",PLoS One,,,True
439ddbbdb17f5ab18ac2e208e7df5c09a8dc9789,PMC,Unexplained diarrhoea in HIV-1 infected individuals,http://dx.doi.org/10.1186/1471-2334-14-22,PMC3925291,24410947,CC BY,"BACKGROUND: Gastrointestinal symptoms, in particular diarrhoea, are common in non-treated HIV-1 infected individuals. Although various enteric pathogens have been implicated, the aetiology of diarrhoea remains unexplained in a large proportion of HIV-1 infected patients. Our aim is to identify the cause of diarrhoea for patients that remain negative in routine diagnostics. METHODS: In this study stool samples of 196 HIV-1 infected persons, including 29 persons with diarrhoea, were examined for enteropathogens and HIV-1. A search for unknown and unexpected viruses was performed using virus discovery cDNA-AFLP combined with Roche-454 sequencing (VIDISCA-454). RESULTS: HIV-1 RNA was detected in stool of 19 patients with diarrhoea (66%) compared to 75 patients (45%) without diarrhoea. In 19 of the 29 diarrhoea cases a known enteropathogen could be identified (66%). Next to these known causative agents, a range of recently identified viruses was identified via VIDISCA-454: cosavirus, Aichi virus, human gyrovirus, and non-A non-B hepatitis virus. Moreover, a novel virus was detected which was named immunodeficiency-associated stool virus (IASvirus). However, PCR based screening for these viruses showed that none of these novel viruses was associated with diarrhoea. Notably, among the 34% enteropathogen-negative cases, HIV-1 RNA shedding in stool was more frequently observed (80%) compared to enteropathogen-positive cases (47%), indicating that HIV-1 itself is the most likely candidate to be involved in diarrhoea. CONCLUSION: Unexplained diarrhoea in HIV-1 infected patients is probably not caused by recently described or previously unknown pathogens, but it is more likely that HIV-1 itself plays a role in intestinal mucosal abnormalities which leads to diarrhoea.",2014 Jan 13,"['Oude Munnink, Bas B', 'Canuti, Marta', 'Deijs, Martin', 'de Vries, Michel', 'Jebbink, Maarten F', 'Rebers, Sjoerd', 'Molenkamp, Richard', 'van Hemert, Formijn J', 'Chung, Kevin', 'Cotten, Matthew', 'Snijders, Fransje', 'Sol, Cees JA', 'van der Hoek, Lia']",BMC Infect Dis,,,True
386c21f11ae0c9199c26218e334373932f3fa0c0,PMC,Profile of international air passengers intercepted with illegal animal products in baggage at Guarulhos and Galeão airports in Brazil,http://dx.doi.org/10.1186/2193-1801-3-69,PMC3925492,24567878,CC BY,"Protection against biological material entering a country or region through airports is important because, through them, infectious agents can quickly reach exotic destinations and be disseminated. Illegal products of animal origin may contain hazardous infectious agents that can compromise animal and public health. The aim of this study was to identify associations between possession of illegal animal products in baggage and demographic characteristics of the passengers, as well as characteristics of their travel plans in the two main Brazilian international airports. A total of 457 passengers were divided into two groups: passengers identified as carrying illegal animal products and control. Passengers identified as carrying illegal animal products not stated on the accompanied baggage declaration completed a questionnaire, to aid in profiling. Nationality, origin, age and residency of passengers were analyzed using chi square, logistic regression and odds ratios. Passengers from Eastern Europe were the most likely to enter with animal products as were those aged between 35 and 55 years. When evaluating the departure point, the highest frequency was seen in those coming from Portugal. Passenger group, reasons for travel, amount and type of baggage were available only for passengers identified as carrying illegal animal products, noting that they prefer traveling alone, for leisure, bringing few bags. Such information can contribute to the early identification of passengers that have illegal animal products in baggage at Brazilian airports.",2014 Feb 6,"['de Melo, Cristiano Barros', 'Pinheiro de Sá, Marcos Eielson', 'Alves, Flaviane Faria', 'McManus, Concepta', 'Aragão, Lucas Fernandes', 'Belo, Bruno Benin', 'Campani, Paulo Ricardo', 'da Matta Ribeiro, Antonio Cavalcanti', 'Seabra, Christina Isoldi', 'Seixas, Luiza']",Springerplus,,,True
a792bbaa94e64b3e7e230718d114dfd5d8d174dd,PMC,Global health in the European Union – a review from an agenda-setting perspective,http://dx.doi.org/10.3402/gha.v7.23610,PMC3925807,24560264,CC BY,"This review attempts to analyse the global health agenda-setting process in the European Union (EU). We give an overview of the European perspective on global health, making reference to the developments that led to the EU acknowledging its role as a global health actor. The article thereby focusses in particular on the European interpretation of its role in global health from 2010, which was formalised through, respectively, a European Commission Communication and European Council Conclusions. Departing from there, and based on Kingdon's multiple streams theory on agenda setting, we identify some barriers that seem to hinder the further establishment and promotion of a solid global health agenda in the EU. The main barriers for creating a strong European global health agenda are the fragmentation of the policy community and the lack of a common definition for global health in Europe. Forwarding the agenda in Europe for global health requires more clarification of the common goals and perspectives of the policy community and the use of arising windows of opportunity.",2014 Feb 13,"['Aluttis, Christoph', 'Krafft, Thomas', 'Brand, Helmut']",Glob Health Action,,,True
0be7b06a39aa31b27514a501ebdd477f42b0919a,PMC,Antifragility and Tinkering in Biology (and in Business) Flexibility Provides an Efficient Epigenetic Way to Manage Risk,http://dx.doi.org/10.3390/genes2040998,PMC3927596,24710302,CC BY,"The notion of antifragility, an attribute of systems that makes them thrive under variable conditions, has recently been proposed by Nassim Taleb in a business context. This idea requires the ability of such systems to ‘tinker’, i.e., to creatively respond to changes in their environment. A fairly obvious example of this is natural selection-driven evolution. In this ubiquitous process, an original entity, challenged by an ever-changing environment, creates variants that evolve into novel entities. Analyzing functions that are essential during stationary-state life yield examples of entities that may be antifragile. One such example is proteins with flexible regions that can undergo functional alteration of their side residues or backbone and thus implement the tinkering that leads to antifragility. This in-built property of the cell chassis must be taken into account when considering construction of cell factories driven by engineering principles.",2011 Nov 29,"['Danchin, Antoine', 'Binder, Philippe M.', 'Noria, Stanislas']",Genes (Basel),,,True
6a2386de99a966c8755732f196ba4c2cc0dda2f2,PMC,Selection of Suitable Reference Genes for Normalization of Quantitative Real-Time Polymerase Chain Reaction in Human Cartilage Endplate of the Lumbar Spine,http://dx.doi.org/10.1371/journal.pone.0088892,PMC3928306,24558443,CC BY,"The quantitative real-time polymerase chain reaction (qRT-PCR) is one of the most widely used methods to study gene expression profiles, and it requires appropriate normalization for accurate and reliable results. Although several genes are commonly used as reference genes (such as GAPDH, ACTB, and 18S rRNA), they are also regulated and can be expressed at varying levels. In this study, we evaluated twelve well-known reference genes to identify the most suitable housekeeping gene for normalization of qRT-PCR in human lumbar vertebral endplate with Modic changes, by using the geNorm, NormFinder, and BestKeeper algorithms. Our results showed that the rarely-used SDHA was the most stable single reference gene, and a combination of three, SDHA, B2M, and LDHA, was the most suitable gene set for normalization in all samples. In addition, the commonly-used genes, GAPDH, ACTB and 18S rRNA, were all inappropriate as internal standards. The rankings of reference genes for the three types of Modic change differed, although SDHA and RPL13A uniformly ranked in the first and last position, respectively. Further simulated expression analysis validated that the arbitrary use of a reference gene could lead to the misinterpretation of data. Our study confirmed the necessity of exploring the expression stability of potential reference genes in each specific tissue and experimental situation before quantitative evaluation of gene expression by qRT-PCR.",2014 Feb 18,"['Zhou, Zhi-Jie', 'Zhang, Jian-Feng', 'Xia, Ping', 'Wang, Ji-Ying', 'Chen, Shuai', 'Fang, Xiang-Qian', 'Fan, Shun-Wu']",PLoS One,,,True
a7ab989eb31d8d6dd0a09da2ee0cf5f6a5182885,PMC,Zoonoses and One Health: A Review of the Literature,http://dx.doi.org/10.1155/2014/874345,PMC3928857,24634782,CC BY,"Background. One health is a concept that was officially adopted by international organizations and scholarly bodies in 1984. It is the notion of combining human, animal, and environmental components to address global health challenges that have an ecological interconnectedness. Methods. A cross-sectional study of the available literature cited was conducted from January 1984 when the one health concept was adopted till December 2012 to examine the role of the one health approach towards zoonoses. Inclusion criteria included publications, professional presentations, funding allocations, official documentation books, and book chapters, and exclusion criteria included those citations written outside the period of review. Results. A total of 737 resources met the inclusion criteria and were considered in this review. Resources showed a continuous upward trend for the years from 2006 to 2012. The predominant resources were journal publications with environmental health as the significant scope focus for one health. There was also an emphasis on the distribution of the work from developed countries. All categories of years, resources, scopes, and country locale differed from the means (P = 0.000). Year of initiative, scope, and country locale showed a dependent relationship (P = 0.022, P = 0.003, and P = 0.021, resp.). Conclusion. Our findings demonstrate the rapid growth in embracing the concept of one health, particularly in developed countries over the past six years. The advantages and benefits of this approach in tackling zoonoses are manifold, yet they are still not seemingly being embraced in developing countries where zoonoses have the greatest impact.",2014 Jan 30,"['Bidaisee, Satesh', 'Macpherson, Calum N. L.']",J Parasitol Res,,,True
ade1a8f088544b34547d3f9608805c969c9f189f,PMC,"The General Composition of the Faecal Virome of Pigs Depends on Age, but Not on Feeding with a Probiotic Bacterium",http://dx.doi.org/10.1371/journal.pone.0088888,PMC3929612,24586429,CC BY,"BACKGROUND: The pig faecal virome, which comprises the community of viruses present in pig faeces, is complex and consists of pig viruses, bacteriophages, transiently passaged plant viruses and other minor virus species. Only little is known about factors influencing its general composition. Here, the effect of the probiotic bacterium Enterococcus faecium (E. faecium) NCIMB 10415 on the pig faecal virome composition was analysed in a pig feeding trial with sows and their piglets, which received either the probiotic bacterium or not. RESULTS: From 8 pooled faecal samples derived from the feeding trial, DNA and RNA virus particles were prepared and subjected to process-controlled Next Generation Sequencing resulting in 390,650 sequence reads. In average, 14% of the reads showed significant sequence identities to known viruses. The percentage of detected mammalian virus sequences was highest (55–77%) in the samples of the youngest piglets and lowest (8–10%) in the samples of the sows. In contrast, the percentage of bacteriophage sequences increased from 22–44% in the youngest piglets to approximately 90% in the sows. The dominating mammalian viruses differed remarkably among 12 day-old piglets (kobuvirus), 54 day-old piglets (boca-, dependo- and pig stool-associated small circular DNA virus [PigSCV]) and the sows (PigSCV, circovirus and “circovirus-like” viruses CB-A and RW-A). In addition, the Shannon index, which reflects the diversity of sequences present in a sample, was generally higher for the sows as compared to the piglets. No consistent differences in the virome composition could be identified between the viromes of the probiotic bacterium-treated group and the control group. CONCLUSION: The analysis indicates that the pig faecal virome shows a high variability and that its general composition is mainly dependent on the age of the pigs. Changes caused by feeding with the probiotic bacterium E. faecium could not be demonstrated using the applied metagenomics method.",2014 Feb 19,"['Sachsenröder, Jana', 'Twardziok, Sven O.', 'Scheuch, Matthias', 'Johne, Reimar']",PLoS One,,,True
f3160710f61d4812ee7b310d0966c3d48ca30d28,PMC,"The General Composition of the Faecal Virome of Pigs Depends on Age, but Not on Feeding with a Probiotic Bacterium",http://dx.doi.org/10.1371/journal.pone.0088888,PMC3929612,24586429,CC BY,"BACKGROUND: The pig faecal virome, which comprises the community of viruses present in pig faeces, is complex and consists of pig viruses, bacteriophages, transiently passaged plant viruses and other minor virus species. Only little is known about factors influencing its general composition. Here, the effect of the probiotic bacterium Enterococcus faecium (E. faecium) NCIMB 10415 on the pig faecal virome composition was analysed in a pig feeding trial with sows and their piglets, which received either the probiotic bacterium or not. RESULTS: From 8 pooled faecal samples derived from the feeding trial, DNA and RNA virus particles were prepared and subjected to process-controlled Next Generation Sequencing resulting in 390,650 sequence reads. In average, 14% of the reads showed significant sequence identities to known viruses. The percentage of detected mammalian virus sequences was highest (55–77%) in the samples of the youngest piglets and lowest (8–10%) in the samples of the sows. In contrast, the percentage of bacteriophage sequences increased from 22–44% in the youngest piglets to approximately 90% in the sows. The dominating mammalian viruses differed remarkably among 12 day-old piglets (kobuvirus), 54 day-old piglets (boca-, dependo- and pig stool-associated small circular DNA virus [PigSCV]) and the sows (PigSCV, circovirus and “circovirus-like” viruses CB-A and RW-A). In addition, the Shannon index, which reflects the diversity of sequences present in a sample, was generally higher for the sows as compared to the piglets. No consistent differences in the virome composition could be identified between the viromes of the probiotic bacterium-treated group and the control group. CONCLUSION: The analysis indicates that the pig faecal virome shows a high variability and that its general composition is mainly dependent on the age of the pigs. Changes caused by feeding with the probiotic bacterium E. faecium could not be demonstrated using the applied metagenomics method.",2014 Feb 19,"['Sachsenröder, Jana', 'Twardziok, Sven O.', 'Scheuch, Matthias', 'Johne, Reimar']",PLoS One,,,False
490ce7b2903c51796088daeeaeac576e76eabcc9,PMC,"The General Composition of the Faecal Virome of Pigs Depends on Age, but Not on Feeding with a Probiotic Bacterium",http://dx.doi.org/10.1371/journal.pone.0088888,PMC3929612,24586429,CC BY,"BACKGROUND: The pig faecal virome, which comprises the community of viruses present in pig faeces, is complex and consists of pig viruses, bacteriophages, transiently passaged plant viruses and other minor virus species. Only little is known about factors influencing its general composition. Here, the effect of the probiotic bacterium Enterococcus faecium (E. faecium) NCIMB 10415 on the pig faecal virome composition was analysed in a pig feeding trial with sows and their piglets, which received either the probiotic bacterium or not. RESULTS: From 8 pooled faecal samples derived from the feeding trial, DNA and RNA virus particles were prepared and subjected to process-controlled Next Generation Sequencing resulting in 390,650 sequence reads. In average, 14% of the reads showed significant sequence identities to known viruses. The percentage of detected mammalian virus sequences was highest (55–77%) in the samples of the youngest piglets and lowest (8–10%) in the samples of the sows. In contrast, the percentage of bacteriophage sequences increased from 22–44% in the youngest piglets to approximately 90% in the sows. The dominating mammalian viruses differed remarkably among 12 day-old piglets (kobuvirus), 54 day-old piglets (boca-, dependo- and pig stool-associated small circular DNA virus [PigSCV]) and the sows (PigSCV, circovirus and “circovirus-like” viruses CB-A and RW-A). In addition, the Shannon index, which reflects the diversity of sequences present in a sample, was generally higher for the sows as compared to the piglets. No consistent differences in the virome composition could be identified between the viromes of the probiotic bacterium-treated group and the control group. CONCLUSION: The analysis indicates that the pig faecal virome shows a high variability and that its general composition is mainly dependent on the age of the pigs. Changes caused by feeding with the probiotic bacterium E. faecium could not be demonstrated using the applied metagenomics method.",2014 Feb 19,"['Sachsenröder, Jana', 'Twardziok, Sven O.', 'Scheuch, Matthias', 'Johne, Reimar']",PLoS One,,,False
43773723e483187647685be053b62f601a8d91d3,PMC,"The General Composition of the Faecal Virome of Pigs Depends on Age, but Not on Feeding with a Probiotic Bacterium",http://dx.doi.org/10.1371/journal.pone.0088888,PMC3929612,24586429,CC BY,"BACKGROUND: The pig faecal virome, which comprises the community of viruses present in pig faeces, is complex and consists of pig viruses, bacteriophages, transiently passaged plant viruses and other minor virus species. Only little is known about factors influencing its general composition. Here, the effect of the probiotic bacterium Enterococcus faecium (E. faecium) NCIMB 10415 on the pig faecal virome composition was analysed in a pig feeding trial with sows and their piglets, which received either the probiotic bacterium or not. RESULTS: From 8 pooled faecal samples derived from the feeding trial, DNA and RNA virus particles were prepared and subjected to process-controlled Next Generation Sequencing resulting in 390,650 sequence reads. In average, 14% of the reads showed significant sequence identities to known viruses. The percentage of detected mammalian virus sequences was highest (55–77%) in the samples of the youngest piglets and lowest (8–10%) in the samples of the sows. In contrast, the percentage of bacteriophage sequences increased from 22–44% in the youngest piglets to approximately 90% in the sows. The dominating mammalian viruses differed remarkably among 12 day-old piglets (kobuvirus), 54 day-old piglets (boca-, dependo- and pig stool-associated small circular DNA virus [PigSCV]) and the sows (PigSCV, circovirus and “circovirus-like” viruses CB-A and RW-A). In addition, the Shannon index, which reflects the diversity of sequences present in a sample, was generally higher for the sows as compared to the piglets. No consistent differences in the virome composition could be identified between the viromes of the probiotic bacterium-treated group and the control group. CONCLUSION: The analysis indicates that the pig faecal virome shows a high variability and that its general composition is mainly dependent on the age of the pigs. Changes caused by feeding with the probiotic bacterium E. faecium could not be demonstrated using the applied metagenomics method.",2014 Feb 19,"['Sachsenröder, Jana', 'Twardziok, Sven O.', 'Scheuch, Matthias', 'Johne, Reimar']",PLoS One,,,False
5926e0775494fcad788d2e93e3a5ddac4d5aeb0d,PMC,Infrastructure and Contamination of the Physical Environment in Three Bangladeshi Hospitals: Putting Infection Control into Context,http://dx.doi.org/10.1371/journal.pone.0089085,PMC3929649,24586516,CC0,"OBJECTIVE: This paper describes the physical structure and environmental contamination in selected hospital wards in three government hospitals in Bangladesh. METHODS: The qualitative research team conducted 48 hours of observation in six wards from three Bangladeshi tertiary hospitals in 2007. They recorded environmental contamination with body secretions and excretions and medical waste and observed ward occupant handwashing and use of personal protective equipment. They recorded number of persons, number of open doors and windows, and use of fans. They measured the ward area and informally observed waste disposal outside the wards. They conducted nine focus group discussions with doctors, nurses and support staff. RESULTS: A median of 3.7 persons were present per 10 m(2) of floor space in the wards. A median of 4.9 uncovered coughs or sneezes were recorded per 10 m(2) per hour per ward. Floors in the wards were soiled with saliva, spit, mucous, vomitus, feces and blood 125 times in 48 hours. Only two of the 12 patient handwashing stations had running water and none had soap. No disinfection was observed before or after using medical instruments. Used medical supplies were often discarded in open containers under the beds. Handwashing with soap was observed in only 32 of 3,373 handwashing opportunities noted during 48 hours. Mosquitoes and feral cats were commonly observed in the wards. CONCLUSIONS: The physical structure and environment of our study hospitals are conducive to the spread of infection to people in the wards. Low-cost interventions on hand hygiene and cleaning procedures for rooms and medical equipment should be developed and evaluated for their practicality and effectiveness.",2014 Feb 19,"['Rimi, Nadia Ali', 'Sultana, Rebeca', 'Luby, Stephen P.', 'Islam, Mohammed Saiful', 'Uddin, Main', 'Hossain, Mohammad Jahangir', 'Zaman, Rashid Uz', 'Nahar, Nazmun', 'Gurley, Emily S.']",PLoS One,,,True
88395bf2fdca68c0eb033b14655275547bdcd714,PMC,Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1,http://dx.doi.org/10.1186/2045-3701-4-3,PMC3930072,24410900,CC BY,"BACKGROUND: Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. Spike (S) protein of SARS-CoV activates the unfolded protein response (UPR). It is not understood whether HCoV-HKU1 S protein has similar activity. In addition, the UPR-activating domain in SARS-CoV S protein remains to be identified. RESULTS: In this study we compared S proteins of SARS-CoV and HCoV-HKU1 for their ability to activate the UPR. Both S proteins were found in the endoplasmic reticulum. Transmembrane serine protease TMPRSS2 catalyzed the cleavage of SARS-CoV S protein, but not the counterpart in HCoV-HKU1. Both S proteins showed a similar pattern of UPR-activating activity. Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. N-linked glycosylation was not required for the activation of the UPR by S proteins. S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 was capable of activating the UPR. A central region (amino acids 201–400) of SARS-CoV S1 was required for this activity. CONCLUSIONS: SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling.",2014 Jan 13,"['Siu, Kam-Leung', 'Chan, Ching-Ping', 'Kok, Kin-Hang', 'Woo, Patrick C-Y', 'Jin, Dong-Yan']",Cell Biosci,,,True
8d2f1769c1de3d813cf910561ff0401fb9d75121,PMC,Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2,http://dx.doi.org/10.1371/journal.ppat.1003932,PMC3930559,24586153,CC BY,"Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.",2014 Feb 20,"['Lemey, Philippe', 'Rambaut, Andrew', 'Bedford, Trevor', 'Faria, Nuno', 'Bielejec, Filip', 'Baele, Guy', 'Russell, Colin A.', 'Smith, Derek J.', 'Pybus, Oliver G.', 'Brockmann, Dirk', 'Suchard, Marc A.']",PLoS Pathog,,,True
52032489740c2f7f90c18e0a2668e5c51a3862a3,PMC,Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2,http://dx.doi.org/10.1371/journal.ppat.1003932,PMC3930559,24586153,CC BY,"Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.",2014 Feb 20,"['Lemey, Philippe', 'Rambaut, Andrew', 'Bedford, Trevor', 'Faria, Nuno', 'Bielejec, Filip', 'Baele, Guy', 'Russell, Colin A.', 'Smith, Derek J.', 'Pybus, Oliver G.', 'Brockmann, Dirk', 'Suchard, Marc A.']",PLoS Pathog,,,False
864891b1bc35a03f305d3294e56b5c0870978f46,PMC,Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2,http://dx.doi.org/10.1371/journal.ppat.1003932,PMC3930559,24586153,CC BY,"Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.",2014 Feb 20,"['Lemey, Philippe', 'Rambaut, Andrew', 'Bedford, Trevor', 'Faria, Nuno', 'Bielejec, Filip', 'Baele, Guy', 'Russell, Colin A.', 'Smith, Derek J.', 'Pybus, Oliver G.', 'Brockmann, Dirk', 'Suchard, Marc A.']",PLoS Pathog,,,False
44c845b602b325eafa4b6a463b08967f456c59fb,PMC,Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2,http://dx.doi.org/10.1371/journal.ppat.1003932,PMC3930559,24586153,CC BY,"Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.",2014 Feb 20,"['Lemey, Philippe', 'Rambaut, Andrew', 'Bedford, Trevor', 'Faria, Nuno', 'Bielejec, Filip', 'Baele, Guy', 'Russell, Colin A.', 'Smith, Derek J.', 'Pybus, Oliver G.', 'Brockmann, Dirk', 'Suchard, Marc A.']",PLoS Pathog,,,False
5061a30dc9fa11fea2c38a44f8e5aaa5f31141fe,PMC,Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2,http://dx.doi.org/10.1371/journal.ppat.1003932,PMC3930559,24586153,CC BY,"Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.",2014 Feb 20,"['Lemey, Philippe', 'Rambaut, Andrew', 'Bedford, Trevor', 'Faria, Nuno', 'Bielejec, Filip', 'Baele, Guy', 'Russell, Colin A.', 'Smith, Derek J.', 'Pybus, Oliver G.', 'Brockmann, Dirk', 'Suchard, Marc A.']",PLoS Pathog,,,False
337e3a24fa905a564211c159d1fc5fc0fd93924d,PMC,Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2,http://dx.doi.org/10.1371/journal.ppat.1003932,PMC3930559,24586153,CC BY,"Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.",2014 Feb 20,"['Lemey, Philippe', 'Rambaut, Andrew', 'Bedford, Trevor', 'Faria, Nuno', 'Bielejec, Filip', 'Baele, Guy', 'Russell, Colin A.', 'Smith, Derek J.', 'Pybus, Oliver G.', 'Brockmann, Dirk', 'Suchard, Marc A.']",PLoS Pathog,,,False
ec5eb5ea6033d1a32e46cb874e3b87b9a700cd5a,PMC,Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2,http://dx.doi.org/10.1371/journal.ppat.1003932,PMC3930559,24586153,CC BY,"Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.",2014 Feb 20,"['Lemey, Philippe', 'Rambaut, Andrew', 'Bedford, Trevor', 'Faria, Nuno', 'Bielejec, Filip', 'Baele, Guy', 'Russell, Colin A.', 'Smith, Derek J.', 'Pybus, Oliver G.', 'Brockmann, Dirk', 'Suchard, Marc A.']",PLoS Pathog,,,True
03fd3a4ec79ffea2a049338b2818457e98496df6,PMC,Comparative In Vivo Analysis of Recombinant Type II Feline Coronaviruses with Truncated and Completed ORF3 Region,http://dx.doi.org/10.1371/journal.pone.0088758,PMC3930587,24586385,CC BY,"Our previous in vitro comparative study on a feline coronavirus (FCoV) pair, differing only in the intactness of their ORF3abc regions, showed that the truncated ORF3abc plays an important role in the efficient macrophage/monocyte tropism of type II feline infectious peritonitis virus (FIPV). In the present study, we describe a challenge experiment with the same recombinant FCoVs in order to gain data on the in vivo characteristics on these viruses. While parent virus FIPV DF-2 developed feline infectious peritonitis in all the infected cats, its recombinant virus PBFIPV-DF-2, differing only in seven nucleotides, proved to be surprisingly low virulent, although caused an acute febrile episode similarly to the original FIPV DF-2. PBFIPV-DF-2 infection induced significantly lower virus neutralization titers than its parent virus, and lacked the second phase of viremia and development of fatal course of the disease. The recombinant PBFIPV-DF-2-R3i with completed ORF3abc gained biological properties that differentiate between the feline enteric coronavirus (FECV) and FIPV biotypes such as intensive replication in the gut, absence of viremia and weak or no serological response. Using reverse genetic approaches our study is the first experimental proof that ORF3abc is indeed responsible for the restriction of FECV replication to the intestine in vivo.",2014 Feb 20,"['Bálint, Ádám', 'Farsang, Attila', 'Zádori, Zoltán', 'Belák, Sándor']",PLoS One,,,True
bb6a9f522a87a780723faca7cde002ece6dbfb48,PMC,A novel reporter system for neutralizing and enhancing antibody assay against dengue virus,http://dx.doi.org/10.1186/1471-2180-14-44,PMC3930823,24548533,CC BY,"BACKGROUND: Dengue virus (DENV) still poses a global public health threat, and no vaccine or antiviral therapy is currently available. Antibody plays distinct roles in controlling DENV infections. Neutralizing antibody is protective against DENV infection, whereas sub-neutralizing concentration of antibody can increase DENV infection, termed antibody-dependent enhancement (ADE). Plaque-based assay represents the most widely accepted method measuring neutralizing or enhancing antibodies. RESULTS: In this study, a novel reporter virus-based system was developed for measuring neutralization and ADE activity. A stable Renilla luciferase reporter DENV (Luc-DENV) that can produce robust luciferase signals in BHK-21 and K562 cells were used to establish the assay and validated against traditional plaque-based assay. Luciferase value analysis using various known DENV-specific monoclonal antibodies showed good repeatability and a well linear correlation with conventional plaque-based assays. The newly developed assay was finally validated with clinical samples from infected animals and individuals. CONCLUSIONS: This reporter virus-based assay for neutralizing and enhancing antibody evaluation is rapid, lower cost, and high throughput, and will be helpful for laboratory detection and epidemiological investigation for DENV antibodies.",2014 Feb 18,"['Song, Ke-Yu', 'Zhao, Hui', 'Jiang, Zhen-You', 'Li, Xiao-Feng', 'Deng, Yong-Qiang', 'Jiang, Tao', 'Zhu, Shun-Ya', 'Shi, Pei-Yong', 'Zhang, Bo', 'Zhang, Fu-Chun', 'Qin, E-De', 'Qin, Cheng-Feng']",BMC Microbiol,,,True
1c857d4493720168ac6eba2bbeb2fbfa31433d91,PMC,Functional Fcgamma Receptor Polymorphisms Are Associated with Human Allergy,http://dx.doi.org/10.1371/journal.pone.0089196,PMC3931680,24586589,CC BY,"OBJECTIVE: IgG Fc receptors (FcγRs) play important roles in immune responses. It is not clear whether FcγR receptors play a role in human asthma and allergy. The aim of current study was to investigate whether functional single nucleotide polymorphisms (SNPs) of FcγR genes (FCGR) are associated with human asthma and allergy. METHODS: Functional SNPs of FCGR2A (FcγRIIA-131His>Arg, rs1801274), FCGR2B (FcγRIIB-187Ile>Thr, rs1050501), FCGR2C (FcγRIIC-13Gln>Stop, rs10917661), FCGR3A (FcγRIIIA-158Val>Phe, rs396991), and FCGR3B variants (FcγRIIIB NA1 and NA2) were genotyped in an asthma family cohort including 370 atopy positive, 239 atopy negative, and 169 asthma positive subjects. The genotype and phenotype data (asthma, bronchial hyper-responsiveness, and atopy) of subjects were analyzed using family-based association tests (FBAT) and logistic regression adjusted for age and sex. RESULT: The FcγRIIA-131His>Arg SNP is significantly associated with atopy in a family-based association test (P = 0.00287) and in a logistic regression analysis (P = 0.0269, OR 0.732, 95% CI: 0.555–0.965). The FcγRIIA-131His (or rs1801274-A) allele capable of binding human IgG2 has a protective role against atopy. In addition, the rare FcγRIIB-187Thr (or rs1050501-C) allele defective for the receptor-mediated inhibitory signals is a risk factor for atopy (P = 0.0031, OR 1.758, 95% CI: 1.209–2.556) and IgE production (P<0.001). However, variants of activating FcγRIIIA (rs396991), and FcγRIIIB (NA1 and NA2), and FcγRIIC (rs10917661) are not associated with asthma, BHR, and atopy (P>0.05). CONCLUSIONS: FcγRIIA and FcγRIIB functional polymorphisms may have a role in the pathogenesis of allergy.",2014 Feb 21,"['Wu, Jianming', 'Lin, Rui', 'Huang, Jinhai', 'Guan, Weihua', 'Oetting, William S.', 'Sriramarao, P.', 'Blumenthal, Malcolm N.']",PLoS One,,,True
e74b146de222afb1af191265d849fc86048712bc,PMC,Nano-ZnO Catalyzed Multicomponent One-Pot Synthesis of Novel Spiro(indoline-pyranodioxine) Derivatives,http://dx.doi.org/10.1155/2014/427195,PMC3933407,24683341,CC BY,"A simple catalytic protocol for the synthesis of novel spiro[indoline-pyranodioxine] derivatives has been developed using ZnO nanoparticle as an efficient, green, and reusable catalyst. The derivatives are obtained in moderate to excellent yield by one-pot three-component reaction of an isatin, malononitrile/ethylcyanoacetate, and 2,2-dimethyl-1,3-dioxane-4,6-dione in absolute ethanol under conventional heating and microwave irradiation. The catalyst was recovered by filtration from the reaction mixture and reused during five consecutive runs without any apparent loss of activity for the same reaction. The mild reaction conditions and recyclability of the catalyst make it environmentally benign synthetic procedure.",2014 Feb 5,"['Sachdeva, Harshita', 'Saroj, Rekha', 'Dwivedi, Diksha']",ScientificWorldJournal,,,True
7f62acc34c68b857a7bf8a4868fdd75d312720e9,PMC,"Population-Based Incidence of Severe Acute Respiratory Virus Infections among Children Aged <5 Years in Rural Bangladesh, June–October 2010",http://dx.doi.org/10.1371/journal.pone.0089978,PMC3934972,24587163,CC0,"BACKGROUND: Better understanding the etiology-specific incidence of severe acute respiratory infections (SARIs) in resource-poor, rural settings will help further develop and prioritize prevention strategies. To address this gap in knowledge, we conducted a longitudinal study to estimate the incidence of SARIs among children in rural Bangladesh. METHODS: During June through October 2010, we followed children aged <5 years in 67 villages to identify those with cough, difficulty breathing, age-specific tachypnea and/or danger signs in the community or admitted to the local hospital. A study physician collected clinical information and obtained nasopharyngeal swabs from all SARI cases and blood for bacterial culture from those hospitalized. We tested swabs for respiratory syncytial virus (RSV), influenza viruses, human metapneumoviruses, adenoviruses and human parainfluenza viruses 1–3 (HPIV) by real-time reverse transcription polymerase chain reaction. We calculated virus-specific SARI incidence by dividing the number of new illnesses by the person-time each child contributed to the study. RESULTS: We followed 12,850 children for 279,029 person-weeks (pw) and identified 141 SARI cases; 76 (54%) at their homes and 65 (46%) at the hospital. RSV was associated with 7.9 SARI hospitalizations per 100,000 pw, HPIV3 2.2 hospitalizations/100,000 pw, and influenza 1.1 hospitalizations/100,000 pw. Among non-hospitalized SARI cases, RSV was associated with 10.8 illnesses/100,000 pw, HPIV3 1.8/100,000 pw, influenza 1.4/100,000 pw, and adenoviruses 0.4/100,000 pw. CONCLUSION: Respiratory viruses, particularly RSV, were commonly associated with SARI among children. It may be useful to explore the value of investing in prevention strategies, such as handwashing and respiratory hygiene, to reduce respiratory infections among young children in such settings.",2014 Feb 25,"['Nasreen, Sharifa', 'Luby, Stephen P.', 'Brooks, W. Abdullah', 'Homaira, Nusrat', 'Mamun, Abdullah Al', 'Bhuiyan, Mejbah Uddin', 'Rahman, Mustafizur', 'Ahmed, Dilruba', 'Abedin, Jaynal', 'Rahman, Mahmudur', 'Alamgir, A. S. M.', 'Fry, Alicia M.', 'Streatfield, Peter Kim', 'Rahman, Anisur', 'Bresee, Joseph', 'Widdowson, Marc-Alain', 'Azziz-Baumgartner, Eduardo']",PLoS One,,,True
540ccda8bb32d2b9192782b878cc2759da109212,PMC,Evolution and Structural Organization of the C Proteins of Paramyxovirinae,http://dx.doi.org/10.1371/journal.pone.0090003,PMC3934983,24587180,CC0,"The phosphoprotein (P) gene of most Paramyxovirinae encodes several proteins in overlapping frames: P and V, which share a common N-terminus (PNT), and C, which overlaps PNT. Overlapping genes are of particular interest because they encode proteins originated de novo, some of which have unknown structural folds, challenging the notion that nature utilizes only a limited, well-mapped area of fold space. The C proteins cluster in three groups, comprising measles, Nipah, and Sendai virus. We predicted that all C proteins have a similar organization: a variable, disordered N-terminus and a conserved, α-helical C-terminus. We confirmed this predicted organization by biophysically characterizing recombinant C proteins from Tupaia paramyxovirus (measles group) and human parainfluenza virus 1 (Sendai group). We also found that the C of the measles and Nipah groups have statistically significant sequence similarity, indicating a common origin. Although the C of the Sendai group lack sequence similarity with them, we speculate that they also have a common origin, given their similar genomic location and structural organization. Since C is dispensable for viral replication, unlike PNT, we hypothesize that C may have originated de novo by overprinting PNT in the ancestor of Paramyxovirinae. Intriguingly, in measles virus and Nipah virus, PNT encodes STAT1-binding sites that overlap different regions of the C-terminus of C, indicating they have probably originated independently. This arrangement, in which the same genetic region encodes simultaneously a crucial functional motif (a STAT1-binding site) and a highly constrained region (the C-terminus of C), seems paradoxical, since it should severely reduce the ability of the virus to adapt. The fact that it originated twice suggests that it must be balanced by an evolutionary advantage, perhaps from reducing the size of the genetic region vulnerable to mutations.",2014 Feb 25,"['Lo, Michael K.', 'Søgaard, Teit Max', 'Karlin, David G.']",PLoS One,,,True
12590435a221d10824ab106e66d0f9fec397db40,PMC,The output of the tRNA modification pathways controlled by the Escherichia coli MnmEG and MnmC enzymes depends on the growth conditions and the tRNA species,http://dx.doi.org/10.1093/nar/gkt1228,PMC3936742,24293650,CC BY,"In Escherichia coli, the MnmEG complex modifies transfer RNAs (tRNAs) decoding NNA/NNG codons. MnmEG catalyzes two different modification reactions, which add an aminomethyl (nm) or carboxymethylaminomethyl (cmnm) group to position 5 of the anticodon wobble uridine using ammonium or glycine, respectively. In [Image: see text] and [Image: see text], however, cmnm(5) appears as the final modification, whereas in the remaining tRNAs, the MnmEG products are converted into 5-methylaminomethyl (mnm(5)) through the two-domain, bi-functional enzyme MnmC. MnmC(o) transforms cmnm(5) into nm(5), whereas MnmC(m) converts nm(5) into mnm(5), thus producing an atypical network of modification pathways. We investigate the activities and tRNA specificity of MnmEG and the MnmC domains, the ability of tRNAs to follow the ammonium or glycine pathway and the effect of mnmC mutations on growth. We demonstrate that the two MnmC domains function independently of each other and that [Image: see text] and [Image: see text] are substrates for MnmC(m), but not MnmC(o). Synthesis of mnm(5)s(2)U by MnmEG-MnmC in vivo avoids build-up of intermediates in [Image: see text]. We also show that MnmEG can modify all the tRNAs via the ammonium pathway. Strikingly, the net output of the MnmEG pathways in vivo depends on growth conditions and tRNA species. Loss of any MnmC activity has a biological cost under specific conditions.",2014 Feb 26,"['Moukadiri, Ismaïl', 'Garzón, M.-José', 'Björk, Glenn R.', 'Armengod, M.-Eugenia']",Nucleic Acids Res,,,True
1d46e668687f5f0244a551b292f5567358f3bf3d,PMC,The output of the tRNA modification pathways controlled by the Escherichia coli MnmEG and MnmC enzymes depends on the growth conditions and the tRNA species,http://dx.doi.org/10.1093/nar/gkt1228,PMC3936742,24293650,CC BY,"In Escherichia coli, the MnmEG complex modifies transfer RNAs (tRNAs) decoding NNA/NNG codons. MnmEG catalyzes two different modification reactions, which add an aminomethyl (nm) or carboxymethylaminomethyl (cmnm) group to position 5 of the anticodon wobble uridine using ammonium or glycine, respectively. In [Image: see text] and [Image: see text], however, cmnm(5) appears as the final modification, whereas in the remaining tRNAs, the MnmEG products are converted into 5-methylaminomethyl (mnm(5)) through the two-domain, bi-functional enzyme MnmC. MnmC(o) transforms cmnm(5) into nm(5), whereas MnmC(m) converts nm(5) into mnm(5), thus producing an atypical network of modification pathways. We investigate the activities and tRNA specificity of MnmEG and the MnmC domains, the ability of tRNAs to follow the ammonium or glycine pathway and the effect of mnmC mutations on growth. We demonstrate that the two MnmC domains function independently of each other and that [Image: see text] and [Image: see text] are substrates for MnmC(m), but not MnmC(o). Synthesis of mnm(5)s(2)U by MnmEG-MnmC in vivo avoids build-up of intermediates in [Image: see text]. We also show that MnmEG can modify all the tRNAs via the ammonium pathway. Strikingly, the net output of the MnmEG pathways in vivo depends on growth conditions and tRNA species. Loss of any MnmC activity has a biological cost under specific conditions.",2014 Feb 26,"['Moukadiri, Ismaïl', 'Garzón, M.-José', 'Björk, Glenn R.', 'Armengod, M.-Eugenia']",Nucleic Acids Res,,,False
e2b6aa71fbb89c9a10e9b00f36313ba5be05b025,PMC,A cypovirus VP5 displays the RNA chaperone-like activity that destabilizes RNA helices and accelerates strand annealing,http://dx.doi.org/10.1093/nar/gkt1256,PMC3936753,24319147,CC BY,"For double-stranded RNA (dsRNA) viruses in the family Reoviridae, their inner capsids function as the machinery for viral RNA (vRNA) replication. Unlike other multishelled reoviruses, cypovirus has a single-layered capsid, thereby representing a simplified model for studying vRNA replication of reoviruses. VP5 is one of the three major cypovirus capsid proteins and functions as a clamp protein to stabilize cypovirus capsid. Here, we expressed VP5 from type 5 Helicoverpa armigera cypovirus (HaCPV-5) in a eukaryotic system and determined that this VP5 possesses RNA chaperone-like activity, which destabilizes RNA helices and accelerates strand annealing independent of ATP. Our further characterization of VP5 revealed that its helix-destabilizing activity is RNA specific, lacks directionality and could be inhibited by divalent ions, such as Mg(2+), Mn(2+), Ca(2+) or Zn(2+), to varying degrees. Furthermore, we found that HaCPV-5 VP5 facilitates the replication initiation of an alternative polymerase (i.e. reverse transcriptase) through a panhandle-structured RNA template, which mimics the 5′-3′ cyclization of cypoviral positive-stranded RNA. Given that the replication of negative-stranded vRNA on the positive-stranded vRNA template necessitates the dissociation of the 5′-3′ panhandle, the RNA chaperone activity of VP5 may play a direct role in the initiation of reoviral dsRNA synthesis.",2014 Feb 5,"['Yang, Jie', 'Cheng, Zhenyun', 'Zhang, Songliu', 'Xiong, Wei', 'Xia, Hongjie', 'Qiu, Yang', 'Wang, Zhaowei', 'Wu, Feige', 'Qin, Cheng-Feng', 'Yin, Lei', 'Hu, Yuanyang', 'Zhou, Xi']",Nucleic Acids Res,,,True
aeb9f61c19077eaf906fd7baf5bcf4e010dc6fa6,PMC,A cypovirus VP5 displays the RNA chaperone-like activity that destabilizes RNA helices and accelerates strand annealing,http://dx.doi.org/10.1093/nar/gkt1256,PMC3936753,24319147,CC BY,"For double-stranded RNA (dsRNA) viruses in the family Reoviridae, their inner capsids function as the machinery for viral RNA (vRNA) replication. Unlike other multishelled reoviruses, cypovirus has a single-layered capsid, thereby representing a simplified model for studying vRNA replication of reoviruses. VP5 is one of the three major cypovirus capsid proteins and functions as a clamp protein to stabilize cypovirus capsid. Here, we expressed VP5 from type 5 Helicoverpa armigera cypovirus (HaCPV-5) in a eukaryotic system and determined that this VP5 possesses RNA chaperone-like activity, which destabilizes RNA helices and accelerates strand annealing independent of ATP. Our further characterization of VP5 revealed that its helix-destabilizing activity is RNA specific, lacks directionality and could be inhibited by divalent ions, such as Mg(2+), Mn(2+), Ca(2+) or Zn(2+), to varying degrees. Furthermore, we found that HaCPV-5 VP5 facilitates the replication initiation of an alternative polymerase (i.e. reverse transcriptase) through a panhandle-structured RNA template, which mimics the 5′-3′ cyclization of cypoviral positive-stranded RNA. Given that the replication of negative-stranded vRNA on the positive-stranded vRNA template necessitates the dissociation of the 5′-3′ panhandle, the RNA chaperone activity of VP5 may play a direct role in the initiation of reoviral dsRNA synthesis.",2014 Feb 5,"['Yang, Jie', 'Cheng, Zhenyun', 'Zhang, Songliu', 'Xiong, Wei', 'Xia, Hongjie', 'Qiu, Yang', 'Wang, Zhaowei', 'Wu, Feige', 'Qin, Cheng-Feng', 'Yin, Lei', 'Hu, Yuanyang', 'Zhou, Xi']",Nucleic Acids Res,,,False
2895e9bc46487b11d2e514ed42fca059df5ec7a6,PMC,Public health human resources: a comparative analysis of policy documents in two Canadian provinces,http://dx.doi.org/10.1186/1478-4491-12-13,PMC3936858,24564931,CC BY,"BACKGROUND: Amidst concerns regarding the capacity of the public health system to respond rapidly and appropriately to threats such as pandemics and terrorism, along with changing population health needs, governments have focused on strengthening public health systems. A key factor in a robust public health system is its workforce. As part of a nationally funded study of public health renewal in Canada, a policy analysis was conducted to compare public health human resources-relevant documents in two Canadian provinces, British Columbia (BC) and Ontario (ON), as they each implement public health renewal activities. METHODS: A content analysis of policy and planning documents from government and public health-related organizations was conducted by a research team comprised of academics and government decision-makers. Documents published between 2003 and 2011 were accessed (BC = 27; ON = 20); documents were either publicly available or internal to government and excerpted with permission. Documentary texts were deductively coded using a coding template developed by the researchers based on key health human resources concepts derived from two national policy documents. RESULTS: Documents in both provinces highlighted the importance of public health human resources planning and policies; this was particularly evident in early post-SARS documents. Key thematic areas of public health human resources identified were: education, training, and competencies; capacity; supply; intersectoral collaboration; leadership; public health planning context; and priority populations. Policy documents in both provinces discussed the importance of an educated, competent public health workforce with the appropriate skills and competencies for the effective and efficient delivery of public health services. CONCLUSION: This policy analysis identified progressive work on public health human resources policy and planning with early documents providing an inventory of issues to be addressed and later documents providing evidence of beginning policy development and implementation. While many similarities exist between the provinces, the context distinctive to each province has influenced and shaped how they have focused their public health human resources policies.",2014 Feb 24,"['Regan, Sandra', 'MacDonald, Marjorie', 'Allan, Diane E', 'Martin, Cheryl', 'Peroff-Johnston, Nancy']",Hum Resour Health,,,True
0245907283f094332e4062539e495f880c6994f6,PMC,Public health human resources: a comparative analysis of policy documents in two Canadian provinces,http://dx.doi.org/10.1186/1478-4491-12-13,PMC3936858,24564931,CC BY,"BACKGROUND: Amidst concerns regarding the capacity of the public health system to respond rapidly and appropriately to threats such as pandemics and terrorism, along with changing population health needs, governments have focused on strengthening public health systems. A key factor in a robust public health system is its workforce. As part of a nationally funded study of public health renewal in Canada, a policy analysis was conducted to compare public health human resources-relevant documents in two Canadian provinces, British Columbia (BC) and Ontario (ON), as they each implement public health renewal activities. METHODS: A content analysis of policy and planning documents from government and public health-related organizations was conducted by a research team comprised of academics and government decision-makers. Documents published between 2003 and 2011 were accessed (BC = 27; ON = 20); documents were either publicly available or internal to government and excerpted with permission. Documentary texts were deductively coded using a coding template developed by the researchers based on key health human resources concepts derived from two national policy documents. RESULTS: Documents in both provinces highlighted the importance of public health human resources planning and policies; this was particularly evident in early post-SARS documents. Key thematic areas of public health human resources identified were: education, training, and competencies; capacity; supply; intersectoral collaboration; leadership; public health planning context; and priority populations. Policy documents in both provinces discussed the importance of an educated, competent public health workforce with the appropriate skills and competencies for the effective and efficient delivery of public health services. CONCLUSION: This policy analysis identified progressive work on public health human resources policy and planning with early documents providing an inventory of issues to be addressed and later documents providing evidence of beginning policy development and implementation. While many similarities exist between the provinces, the context distinctive to each province has influenced and shaped how they have focused their public health human resources policies.",2014 Feb 24,"['Regan, Sandra', 'MacDonald, Marjorie', 'Allan, Diane E', 'Martin, Cheryl', 'Peroff-Johnston, Nancy']",Hum Resour Health,,,False
2bfe733ac66d7514f07e3c7ceb2a58dea87f922b,PMC,Public health human resources: a comparative analysis of policy documents in two Canadian provinces,http://dx.doi.org/10.1186/1478-4491-12-13,PMC3936858,24564931,CC BY,"BACKGROUND: Amidst concerns regarding the capacity of the public health system to respond rapidly and appropriately to threats such as pandemics and terrorism, along with changing population health needs, governments have focused on strengthening public health systems. A key factor in a robust public health system is its workforce. As part of a nationally funded study of public health renewal in Canada, a policy analysis was conducted to compare public health human resources-relevant documents in two Canadian provinces, British Columbia (BC) and Ontario (ON), as they each implement public health renewal activities. METHODS: A content analysis of policy and planning documents from government and public health-related organizations was conducted by a research team comprised of academics and government decision-makers. Documents published between 2003 and 2011 were accessed (BC = 27; ON = 20); documents were either publicly available or internal to government and excerpted with permission. Documentary texts were deductively coded using a coding template developed by the researchers based on key health human resources concepts derived from two national policy documents. RESULTS: Documents in both provinces highlighted the importance of public health human resources planning and policies; this was particularly evident in early post-SARS documents. Key thematic areas of public health human resources identified were: education, training, and competencies; capacity; supply; intersectoral collaboration; leadership; public health planning context; and priority populations. Policy documents in both provinces discussed the importance of an educated, competent public health workforce with the appropriate skills and competencies for the effective and efficient delivery of public health services. CONCLUSION: This policy analysis identified progressive work on public health human resources policy and planning with early documents providing an inventory of issues to be addressed and later documents providing evidence of beginning policy development and implementation. While many similarities exist between the provinces, the context distinctive to each province has influenced and shaped how they have focused their public health human resources policies.",2014 Feb 24,"['Regan, Sandra', 'MacDonald, Marjorie', 'Allan, Diane E', 'Martin, Cheryl', 'Peroff-Johnston, Nancy']",Hum Resour Health,,,False
69e95489dff0da006349ceb3a46a1f215cb1b910,PMC,"Myosins 1 and 6, myosin light chain kinase, actin and microtubules cooperate during antibody-mediated internalisation and trafficking of membrane-expressed viral antigens in feline infectious peritonitis virus infected monocytes",http://dx.doi.org/10.1186/1297-9716-45-17,PMC3937040,24517254,CC BY,"Monocytes infected with feline infectious peritonitis virus, a coronavirus, express viral proteins in their plasma membranes. Upon binding of antibodies, these proteins are quickly internalised through a new clathrin- and caveolae-independent internalisation pathway. By doing so, the infected monocytes can escape antibody-dependent cell lysis. In the present study, we investigated which kinases and cytoskeletal proteins are of importance during internalisation and subsequent intracellular transport. The experiments showed that myosin light chain kinase (MLCK) and myosin 1 are crucial for the initiation of the internalisation. With co-localisation stainings, it was found that MLCK and myosin 1 co-localise with antigens even before internalisation started. Myosin 6 co-localised with the internalising complexes during passage through the cortical actin, were it might play a role in moving or disintegrating actin filaments, to overcome the actin barrier. One minute after internalisation started, vesicles had passed the cortical actin, co-localised with microtubules and association with myosin 6 was lost. The vesicles were further transported over the microtubules and accumulated at the microtubule organising centre after 10 to 30 min. Intracellular trafficking over microtubules was mediated by MLCK, myosin 1 and a small actin tail. Since inhibiting MLCK with ML-7 was so efficient in blocking the internalisation pathway, this target can be used for the development of a new treatment for FIPV.",2014 Feb 12,"['Dewerchin, Hannah L', 'Desmarets, Lowiese M', 'Noppe, Ytse', 'Nauwynck, Hans J']",Vet Res,,,True
4e741d57fb2db417d3a82fae701233ed7d4c5b55,PMC,Chinese immigrant parents’ vaccination decision making for children: a qualitative analysis,http://dx.doi.org/10.1186/1471-2458-14-133,PMC3937074,24507384,CC BY,"BACKGROUND: While immunization coverage rates for childhood routine vaccines in Hong Kong are almost 100%, the uptake rates of optional vaccines remain suboptimal. Understanding parental decision-making for children’s vaccination is important, particularly among minority groups who are most vulnerable and underserved. This study explored how a subsample of new immigrant mothers from mainland China, a rapidly-growing subpopulation in Hong Kong, made decisions on various childhood and adolescent vaccines for their offspring, and identified key influences affecting their decision making. METHODS: Semi-structured in-depth interviews were conducted with 23 Chinese new immigrant mothers recruited by purposive sampling. All interviews were audio-taped, transcribed and analyzed using a Grounded Theory approach. RESULTS: Participants’ conversation revealed five underlying themes which influenced parents’ vaccination decision-making: (1) Institutional factors, (2) Insufficient vaccination knowledge and advice, (3) Affective impacts on motivation, (4) Vaccination barriers, and (5) Social influences. The role of social norms appeared overwhelmingly salient influencing parents’ vaccination decision making. Institutional factors shaped parent’s perceptions of vaccination necessity. Fear of vaccine-targeted diseases was a key motivating factor for parents adopting vaccination. Insufficient knowledge about vaccines and targeted diseases, lack of advice from health professionals and, if provided, suspicions regarding the motivations for such advice were common issues. Vaccination cost was a major barrier for many new immigrant parents. CONCLUSIONS: Social norms play a key role influencing parental vaccination decision-making. Insight gained from this study will help inform healthcare providers in vaccination communication and policymakers in future vaccination programme.",2014 Feb 7,"['Wang, Linda DL', 'Lam, Wendy WT', 'Wu, Joseph T', 'Liao, Qiuyan', 'Fielding, Richard']",BMC Public Health,,,True
fd28c322b33337c09ccb3d0785d8c2494efa0946,PMC,Rapid PCR/ESI-MS-based molecular genotyping of Staphylococcus aureus from nasal swabs of emergency department patients,http://dx.doi.org/10.1186/1471-2334-14-16,PMC3937163,24405766,CC BY,"BACKGROUND: A limitation of both culture-based and molecular methods of screening for staphylococcal infection is that current tests determine only the presence or absence of colonization with no information on the colonizing strain type. A technique that couples polymerase chain reaction to mass spectrometry (PCR/ESI-MS) has recently been developed and an assay validated to identify and genotype S. aureus and coagulase-negative staphylococci (CoNS). METHODS: This study was conducted to determine the rates, risk factors, and molecular genotypes of colonizing Staphylococcus aureus in adult patients presenting to an inner-city academic emergency department. Participants completed a structured questionnaire to assess hospital and community risks for infection with methicillin-resistant S. aureus (MRSA). Nasal swabs were analyzed by PCR/ESI-MS to identify and genotype S. aureus and CoNS. RESULTS: Of 200 patients evaluated, 59 were colonized with S. aureus; 27 of these were methicillin-resistant strains. Twenty-four of the 59 S. aureus carriers were co-colonized with a CoNS and 140 of the 200 patients were colonized exclusively with CoNS. The molecular genotypes of the 59 S. aureus strains were diverse; 21 unique molecular genotypes belonging to seven major clonal complexes were identified. Eighty-five of 200 patients carried strains with high-level mupirocin resistance. Of these eighty-five participants, 4 were colonized exclusively with S. aureus, 16 were co-colonized with S. aureus and CoNS, and 65 were colonized exclusively with CoNS. CONCLUSION: The prevalence of S. aureus and methicillin-resistant S. aureus colonization in a random sample of patients seeking care in Emergency Department was 29.5% and 13.5%, respectively. A substantial fraction of the S. aureus-colonized patients were co-colonized with CoNS and high-level mupirocin-resistant CoNS. Determining the molecular genotype of S. aureus during intake screening may prove valuable in the future if certain molecular genotypes become associated with increased infection risk.",2014 Jan 9,"['Kecojevic, Aleksandar', 'Ranken, Ray', 'Ecker, David J', 'Massire, Christian', 'Sampath, Rangarajan', 'Blyn, Lawrence B', 'Hsieh, Yu-Hsiang', 'Rothman, Richard E', 'Gaydos, Charlotte A']",BMC Infect Dis,,,True
0b22db40e9e78fb29f6ae2938ed8ee2d00cd46b2,PMC,Disassembly of the cystovirus ϕ6 envelope by montmorillonite clay,http://dx.doi.org/10.1002/mbo3.148,PMC3937728,24357622,CC BY,"Prior studies of clay–virus interactions have focused on the stability and infectivity of nonenveloped viruses, yielding contradictory results. We hypothesize that the surface charge distribution of the clay and virus envelope dictates how the components react and affect aggregation, viral stability, and infectivity. The bacteriophage Cystoviridae species φ6 used in this study is a good model for enveloped pathogens. The interaction between φ6 and montmorillonite (MMT) clay (the primary component of bentonite) is explored by transmission electron microscopy. The analyses show that MMT–φ6 mixtures undergo heteroaggregation, forming structures in which virtually all the virions are either sequestered between MMT platelet layers or attached to platelet edges. The virions swell and undergo disassembly resulting in partial or total envelope loss. Edge-attached viral envelopes distort to increase contact area with the positively charged platelet edges indicating that the virion surface is negatively charged. The nucleocapsid (NCs) remaining after envelope removal also exhibit distortion, in contrast to detergent-produced NCs which exhibit no distortion. This visually discernible disassembly is a mechanism for loss of infectivity previously unreported by studies of nonenveloped viruses. The MMT-mediated sequestration and disassembly result in reduced infectivity, suggesting that clays may reduce infectivity of enveloped pathogenic viruses in soils and sediments.",2014 Feb 19,"['Block, Karin A', 'Trusiak, Adrianna', 'Katz, Al', 'Gottlieb, Paul', 'Alimova, Alexandra', 'Wei, Hui', 'Morales, Jorge', 'Rice, William J', 'Steiner, Jeffrey C']",Microbiologyopen,,,True
22977df2b5a35dfe536faa4bd77a21ab316dc9f8,PMC,Long-Term Single-Dose Efficacy of a Vesicular Stomatitis Virus-Based Andes Virus Vaccine in Syrian Hamsters,http://dx.doi.org/10.3390/v6020516,PMC3939469,24492621,CC BY,"Andes virus (ANDV) is highly pathogenic in humans and is the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in South America. Case-fatality rates are as high as 50% and there are no approved vaccines or specific therapies for infection. Our laboratory has recently developed a replication-competent recombinant vesicular stomatitis virus (VSV)-based vaccine that expressed the glycoproteins of Andes virus in place of the native VSV glycoprotein (G). This vaccine is highly efficacious in the Syrian hamster model of HCPS when given 28 days before challenge with ANDV, or when given around the time of challenge (peri-exposure), and even protects when administered post-exposure. Herein, we sought to test the durability of the immune response to a single dose of this vaccine in Syrian hamsters. This vaccine was efficacious in hamsters challenged intranasally with ANDV 6 months after vaccination (p = 0.025), but animals were not significantly protected following 1 year of vaccination (p = 0.090). The decrease in protection correlated with a reduction of measurable neutralizing antibody responses, and suggests that a more robust vaccination schedule might be required to provide long-term immunity.",2014 Jan 31,"['Prescott, Joseph', 'DeBuysscher, Blair L.', 'Brown, Kyle S.', 'Feldmann, Heinz']",Viruses,,,True
b76a42e03efa0717d687c09551b0fb2a3cf116b9,PMC,Molecular Analysis of Human Metapneumovirus Detected in Patients with Lower Respiratory Tract Infection in Upper Egypt,http://dx.doi.org/10.1155/2014/290793,PMC3941176,24669221,CC BY,"Introduction. Since 2001, when Human metapneumovirus (HMPV) was isolated in the Netherlands, the virus has been detected in several continents. Although reports have confirmed the prevalence of HMPV worldwide, data from Egypt remain limited. HMPV plays an important role in respiratory tract infections in individuals of all ages particularly in children. This study was aimed at estimating the prevalence of HMPV in patients with community-acquired lower respiratory infection in Upper Egypt and characterizing the circulating Egyptian HMPV strains for the first time. Materials and Methods. From 2005 to 2008, respiratory samples from 520 patients were analyzed for the presence of HMPV by real-time RT-PCR. Molecular and phylogenetic analyses were performed on partial fusion gene sequences of HMPV-positive patients. Results. HMPV-positive patients were detected in 2007-2008. The overall infection rate was 4%, while 57% of the patients were children. Sequence analysis demonstrated circulation of subgroup B viruses with predominance of lineage B2. Nucleotide sequence identity within lineage B1 was 98.8%–99.7% and higher than that in lineage B2 (94.3%–100%). Three new amino acid substitutions (T223N, R229K, and D280N) of lineage B2 were observed. Conclusion. HMPV is a major viral pathogen in the Egyptian population especially in children. During 2007-2008, predominantly HMPV B2 circulated in Upper Egypt.",2014 Jan 30,"['Embarek Mohamed, Mona S.', 'Reiche, Janine', 'Jacobsen, Sonja', 'Thabit, Amany G.', 'Badary, Mohamed S.', 'Brune, Wolfram', 'Schweiger, Brunhilde', 'Osmann, Ahmed H.']",Int J Microbiol,,,True
4d2c66f3c30a2fd8f14f75c3f5405e2ba61b9345,PMC,Giardiosis and other enteropathogenic infections: a study on diarrhoeic calves in Southern Germany,http://dx.doi.org/10.1186/1756-0500-7-112,PMC3941484,24568139,CC BY,"BACKGROUND: Diarrhoea induces massive problems in the rearing of calves. The aim of the study was to obtain current data about the frequency of Giardia spp., Cryptosporidium spp. and Eimeria spp. in diarrhoeic calves in Southern Germany with the particular focus on giardiosis. RESULTS: 1564 samples were analysed for the three pathogens using microscopical methods. Giardia spp. was detectable in 112/1564 samples (7.2%). The mean age was 46.5 days and the odds of being infected with Giardia spp. increased slowly up to 8 times from about 12 days to 30 days of age. There appeared to be no seasonal influence on the frequency of Giardia spp. A mono-infection with Giardia spp. was diagnosed in 46 calves (2.9%) whereas 15 calves (1.0%) had a mixed-infection with Cryptosporidium spp. and 51 calves (3.3%) with Eimeria spp. Cryptosporidium spp. and Eimeria spp. could be detected in 646/1564 samples (41.3%) and 208/1564 samples (13.3%), respectively, with a mean age of 11.3 and 55.0 days, respectively. The odds of being infected with Cryptosporidium spp. increased up to 4.5 times until an age of 10 days. After that the odds decreased continuously and was approaching zero at about 30 days. The odds of being infected with Eimeria spp. increased continuously up to 30 times from about 20 days to 60 days of age. There appeared to be no significant seasonal influence on the frequency of Cryptosporidium spp.; but there was one for Eimeria spp.: the odds of being infected with Eimeria spp. in March and April decreased by about half and increased up to 2.3 times between July and September. Additionally, as requested by the veterinarians, 1282 of those samples were analysed for E. coli, Rota-, Coronavirus and Cryptosporidium spp. using an ELISA. Obtained frequencies for these pathogens were 0.9%, 37.8%, 3.4% and 45.3% with a mean age of 24.8 days, 12.1 days, 9.0 days and 12.1 days, respectively. CONCLUSIONS: The results indicate that in Southern Germany in addition to Eimeria spp., Giardia spp. seems to play a contributing role in diarrhoea in older calves, whereas Cryptosporidium spp. and Rotavirus are mostly relevant in young calves.",2014 Feb 26,"['Gillhuber, Julia', 'Rügamer, David', 'Pfister, Kurt', 'Scheuerle, Miriam C']",BMC Res Notes,,,True
a62951116b1815c48334c0caae599e4d4f06e58f,PMC,In Vitro Anti-rotaviral Activity of Achillea kellalensis,,PMC3941895,24624203,CC BY,"BACKGROUND: Achillea kellalensis, which is frequently used by Chaharmahal va Bakhtiarians residing in, Southwest of Iran, as a traditional herbal medicine for the treatment of acute diarrhea, has been selected to examine its antiviral activities against bovine rotavirus and cell toxicity activity in MA-104 cells. OBJECTIVES: The aim of this study was to evaluate the in vitro cytotoxic and anti-rotavirus properties of crude extracts of A. kellalensis. MATERIALS AND METHODS: The dried and powdered flowers of Achillea kellalensis were extracted with hot water and ethanol 50% (v/v). The cell viability and toxicity of the extracts were evaluated on MA-104 cells using four methods; trypan blue dye, NR, crystal violet and MTT assay. The in vitro anti-rotavirus properties were determined via four different assays, in order to evaluate the direct inhibition and/or the inhibition of viral replication. RESULTS: Cytotoxicity of two A. kellalensis extracts showed different concentrations. Hydro-alcoholic extract had low CC(50) at 600 µg/mL by the NR assay while the aqueous extract had high CC(50) at 1000µg/mL by the crystal violet method. In the simultaneous treatment assay and post treatment assay, the extracts were able to prevent viral replication and inhibit the viral CPE on MA-104 cells at 10 TCID(50), but the extracts did not exhibit direct antiviral activity on rotavirus adsorption. The effective concentration (EC(50)) of both extracts was observed to be 100 µg/mL. CONCLUSIONS: These results indicate that A. kellalensis extracts exert potent anti-rotaviral activity only after viral adsorption. The two extracts from A. kellalensis showed a good selectivity index. Also these results suggest that extracts prepared from the flowers of A. kellalensis may be potential anti-rotaviral agents in vivo and be useful in veterinary medicine.",2013 Aug 17,"['Taherkhani, Reza', 'Farshadpour, Fatemeh', 'Makvandi, Manoochehr']",Jundishapur J Nat Pharm Prod,,,True
7c1647ec918ab799e8f2dc782620024844c52a55,PMC,DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial,http://dx.doi.org/10.1186/1471-2431-14-37,PMC3942179,24506910,CC BY,"BACKGROUND: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of ‘high dose’ (2000 IU/day) vs. ‘standard dose’ (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of ‘high dose’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI. METHODS/DESIGN: This study is a pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1–5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be randomized to the ‘standard dose’ or ‘high dose’ oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. DISCUSSION: Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers.",2014 Feb 8,"['Maguire, Jonathon L', 'Birken, Catherine S', 'Loeb, Mark B', 'Mamdani, Muhammad', 'Thorpe, Kevin', 'Hoch, Jeffrey S', 'Mazzulli, Tony', 'Borkhoff, Cornelia M', 'Macarthur, Colin', 'Parkin, Patricia C']",BMC Pediatr,,,True
f4abc6948ca4fa09dcedeb1fd26eefd79011d9c2,PMC,DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial,http://dx.doi.org/10.1186/1471-2431-14-37,PMC3942179,24506910,CC BY,"BACKGROUND: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of ‘high dose’ (2000 IU/day) vs. ‘standard dose’ (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of ‘high dose’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI. METHODS/DESIGN: This study is a pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1–5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be randomized to the ‘standard dose’ or ‘high dose’ oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. DISCUSSION: Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers.",2014 Feb 8,"['Maguire, Jonathon L', 'Birken, Catherine S', 'Loeb, Mark B', 'Mamdani, Muhammad', 'Thorpe, Kevin', 'Hoch, Jeffrey S', 'Mazzulli, Tony', 'Borkhoff, Cornelia M', 'Macarthur, Colin', 'Parkin, Patricia C']",BMC Pediatr,,,False
100f1ef9121b891657828073c30b4729e7f114de,PMC,DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial,http://dx.doi.org/10.1186/1471-2431-14-37,PMC3942179,24506910,CC BY,"BACKGROUND: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of ‘high dose’ (2000 IU/day) vs. ‘standard dose’ (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of ‘high dose’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI. METHODS/DESIGN: This study is a pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1–5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be randomized to the ‘standard dose’ or ‘high dose’ oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. DISCUSSION: Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers.",2014 Feb 8,"['Maguire, Jonathon L', 'Birken, Catherine S', 'Loeb, Mark B', 'Mamdani, Muhammad', 'Thorpe, Kevin', 'Hoch, Jeffrey S', 'Mazzulli, Tony', 'Borkhoff, Cornelia M', 'Macarthur, Colin', 'Parkin, Patricia C']",BMC Pediatr,,,False
6728e39493edf4ca2fcc3f1a94a96cb7d12e5196,PMC,DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial,http://dx.doi.org/10.1186/1471-2431-14-37,PMC3942179,24506910,CC BY,"BACKGROUND: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of ‘high dose’ (2000 IU/day) vs. ‘standard dose’ (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of ‘high dose’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI. METHODS/DESIGN: This study is a pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1–5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be randomized to the ‘standard dose’ or ‘high dose’ oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. DISCUSSION: Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers.",2014 Feb 8,"['Maguire, Jonathon L', 'Birken, Catherine S', 'Loeb, Mark B', 'Mamdani, Muhammad', 'Thorpe, Kevin', 'Hoch, Jeffrey S', 'Mazzulli, Tony', 'Borkhoff, Cornelia M', 'Macarthur, Colin', 'Parkin, Patricia C']",BMC Pediatr,,,False
e42319fcc00ed3b44add5b145465dafbd56380b7,PMC,DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial,http://dx.doi.org/10.1186/1471-2431-14-37,PMC3942179,24506910,CC BY,"BACKGROUND: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of ‘high dose’ (2000 IU/day) vs. ‘standard dose’ (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of ‘high dose’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI. METHODS/DESIGN: This study is a pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1–5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be randomized to the ‘standard dose’ or ‘high dose’ oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. DISCUSSION: Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers.",2014 Feb 8,"['Maguire, Jonathon L', 'Birken, Catherine S', 'Loeb, Mark B', 'Mamdani, Muhammad', 'Thorpe, Kevin', 'Hoch, Jeffrey S', 'Mazzulli, Tony', 'Borkhoff, Cornelia M', 'Macarthur, Colin', 'Parkin, Patricia C']",BMC Pediatr,,,False
ecbb9acde61473bf4f5942d6bbef461eee034a9a,PMC,DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial,http://dx.doi.org/10.1186/1471-2431-14-37,PMC3942179,24506910,CC BY,"BACKGROUND: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of ‘high dose’ (2000 IU/day) vs. ‘standard dose’ (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of ‘high dose’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI. METHODS/DESIGN: This study is a pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1–5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be randomized to the ‘standard dose’ or ‘high dose’ oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. DISCUSSION: Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers.",2014 Feb 8,"['Maguire, Jonathon L', 'Birken, Catherine S', 'Loeb, Mark B', 'Mamdani, Muhammad', 'Thorpe, Kevin', 'Hoch, Jeffrey S', 'Mazzulli, Tony', 'Borkhoff, Cornelia M', 'Macarthur, Colin', 'Parkin, Patricia C']",BMC Pediatr,,,False
d5cc1936183d8b73aa5006487dce09b3f8fe1d65,PMC,Transcriptome Analysis of the Initial Stage of Acute WSSV Infection Caused by Temperature Change,http://dx.doi.org/10.1371/journal.pone.0090732,PMC3942461,24595043,CC BY,"White spot syndrome virus (WSSV) is the most devastating virosis threatening the shrimp culture industry worldwide. Variations of environmental factors in shrimp culture ponds usually lead to the outbreak of white spot syndrome (WSS). In order to know the molecular mechanisms of WSS outbreak induced by temperature variation and the biological changes of the host at the initial stage of WSSV acute infection, RNA-Seq technology was used to analyze the differentially expressed genes (DEGs) in shrimp with a certain amount of WSSV cultured at 18°C and shrimp whose culture temperature were raised to 25°C. To analyze whether the expression changes of the DEGs were due to temperature rising or WSSV proliferation, the expression of selected DEGs was analyzed by real-time PCR with another shrimp group, namely Group T, as control. Group T didn’t suffer WSSV infection but was subjected to temperature rising in parallel. At the initial stage of WSSV acute infection, DEGs related to energy production were up-regulated, whereas most DEGs related to cell cycle and positive regulation of cell death and were down-regulated. Triose phosphate isomerase, enolase and alcohol dehydrogenase involved in glycosis were up-regulated, while pyruvate dehydrogenase, citrate synthase and isocitrate dehydrogenase with NAD as the coenzyme involved in TCA pathway were down-regulated. Also genes involved in host DNA replication, including DNA primase, DNA topoisomerase and DNA polymerase showed down-regulated expression. Several interesting genes including crustin genes, acting binding or inhibiting protein genes, a disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) gene and a GRP 78 gene were also analyzed. Understanding the interactions between hosts and WSSV at the initial stage of acute infection will not only help to get a deep insight into the pathogenesis of WSSV but also provide clues for therapies.",2014 Mar 4,"['Sun, Yumiao', 'Li, Fuhua', 'Sun, Zheng', 'Zhang, Xiaojun', 'Li, Shihao', 'Zhang, Chengsong', 'Xiang, Jianhai']",PLoS One,,,True
6b40e3b543867aa91f5d01345cf3ed074300159c,PMC,Genome-Wide Analysis of Codon Usage and Influencing Factors in Chikungunya Viruses,http://dx.doi.org/10.1371/journal.pone.0090905,PMC3942501,24595095,CC BY,"Chikungunya virus (CHIKV) is an arthropod-borne virus of the family Togaviridae that is transmitted to humans by Aedes spp. mosquitoes. Its genome comprises a 12 kb single-strand positive-sense RNA. In the present study, we report the patterns of synonymous codon usage in 141 CHIKV genomes by calculating several codon usage indices and applying multivariate statistical methods. Relative synonymous codon usage (RSCU) analysis showed that the preferred synonymous codons were G/C and A-ended. A comparative analysis of RSCU between CHIKV and its hosts showed that codon usage patterns of CHIKV are a mixture of coincidence and antagonism. Similarity index analysis showed that the overall codon usage patterns of CHIKV have been strongly influenced by Pan troglodytes and Aedes albopictus during evolution. The overall codon usage bias was low in CHIKV genomes, as inferred from the analysis of effective number of codons (ENC) and codon adaptation index (CAI). Our data suggested that although mutation pressure dominates codon usage in CHIKV, patterns of codon usage in CHIKV are also under the influence of natural selection from its hosts and geography. To the best of our knowledge, this is first report describing codon usage analysis in CHIKV genomes. The findings from this study are expected to increase our understanding of factors involved in viral evolution, and fitness towards hosts and the environment.",2014 Mar 4,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Tong, Yigang']",PLoS One,,,True
2e83f16bbbc37d4cf2eba3dd0479e4ec7da6fc41,PMC,LBSapSal-vaccinated dogs exhibit increased circulating T-lymphocyte subsets (CD4(+) and CD8(+)) as well as a reduction of parasitism after challenge with Leishmania infantum plus salivary gland of Lutzomyia longipalpis,http://dx.doi.org/10.1186/1756-3305-7-61,PMC3943450,24507702,CC BY,"BACKGROUND: The development of a protective vaccine against canine visceral leishmaniasis (CVL) is an alternative approach for interrupting the domestic cycle of Leishmania infantum. Given the importance of sand fly salivary proteins as potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in the last few decades. In this context, we previously immunized dogs with a vaccine composed of L. braziliensis antigens plus saponin as the adjuvant and sand fly salivary gland extract (LBSapSal vaccine). This vaccine elicited an increase in both anti-saliva and anti-Leishmania IgG isotypes, higher counts of specific circulating CD8(+) T cells, and high NO production. METHODS: We investigated the immunogenicity and protective effect of LBSapSal vaccination after intradermal challenge with 1 × 10(7) late-log-phase L. infantum promastigotes in the presence of sand fly saliva of Lutzomyia longipalpis. The dogs were followed for up to 885 days after challenge. RESULTS: The LBSapSal vaccine presents extensive antigenic diversity with persistent humoral and cellular immune responses, indicating resistance against CVL is triggered by high levels of total IgG and its subtypes (IgG1 and IgG2); expansion of circulating CD5(+), CD4(+), and CD8(+) T lymphocytes and is Leishmania-specific; and reduction of splenic parasite load. CONCLUSIONS: These results encourage further study of vaccine strategies addressing Leishmania antigens in combination with proteins present in the saliva of the vector.",2014 Feb 7,"['Aguiar-Soares, Rodrigo Dian de Oliveira', 'Roatt, Bruno Mendes', 'Ker, Henrique Gama', 'Moreira, Nádia das Dores', 'Mathias, Fernando Augusto Siqueira', 'Cardoso, Jamille Mirelle de Oliveira', 'Gontijo, Nelder Figueiredo', 'Bruna-Romero, Oscar', 'Teixeira-Carvalho, Andréa', 'Martins-Filho, Olindo Assis', 'Corrêa-Oliveira, Rodrigo', 'Giunchetti, Rodolfo Cordeiro', 'Reis, Alexandre Barbosa']",Parasit Vectors,,,True
a22be780c7774b48b0f4415ed03d2e62ee098518,PMC,A Chemoinformatics Approach to the Discovery of Lead-Like Molecules from Marine and Microbial Sources En Route to Antitumor and Antibiotic Drugs,http://dx.doi.org/10.3390/md12020757,PMC3944514,24473174,CC BY,"The comprehensive information of small molecules and their biological activities in the PubChem database allows chemoinformatic researchers to access and make use of large-scale biological activity data to improve the precision of drug profiling. A Quantitative Structure–Activity Relationship approach, for classification, was used for the prediction of active/inactive compounds relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1804 compounds from PubChem. Using the best classification models for antibiotic and antitumor activities a data set of marine and microbial natural products from the AntiMarin database were screened—57 and 16 new lead compounds for antibiotic and antitumor drug design were proposed, respectively. All compounds proposed by our approach are classified as non-antibiotic and non-antitumor compounds in the AntiMarin database. Recently several of the lead-like compounds proposed by us were reported as being active in the literature.",2014 Jan 27,"['Pereira, Florbela', 'Latino, Diogo A. R. S.', 'Gaudêncio, Susana P.']",Mar Drugs,,,True
f4237ea9635b4330639d7f678c719a05f7c9d8a3,PMC,Genetic characterization of type 2a canine parvoviruses from Taiwan reveals the emergence of an Ile324 mutation in VP2,http://dx.doi.org/10.1186/1743-422X-11-39,PMC3944821,24568207,CC BY,"BACKGROUND: Canine parvovirus 2 (CPV 2) is a major infectious cause of mortality in puppies. The characteristic symptom of CPV 2 disease is intestinal hemorrhage with severe bloody diarrhea. Soon after CPV was first recognized in the late 1970s, the original virus, CPV 2, was replaced in the canine population by strains carrying minor antigenic variants (termed 2a, 2b, and 2c) of the VP2 gene that could be distinguished using monoclonal antibodies and molecular analyses. Here, we provide an updated molecular characterization of the CPV 2 circulating in Taiwan. METHODS: In this study, 28 isolates of CPV 2 from 144 dogs with suspected CPV infection were obtained from northern, central, and southern Taiwan from 2008 to 2012 and screened by PCR. The 28 isolates were sequenced, and a phylogenetic analysis of the VP2 gene was performed. RESULTS: Of the 28 Taiwanese CPV 2 isolates, 15 were identified as new CPV 2a, and 13 were identified as new CPV 2b. Compared to the reference CPV 2a, all 15 of the CPV 2a sequences collected in this study contain an Ile324 mutation caused by a TAT to ATT mutation at nucleotides 970–972 of the VP2 gene. CONCLUSION: Our VP2 sequence data revealed that both types are currently prevalent CPV 2 field strains circulating in Taiwan, and a unique Ile324 VP2 mutation was found in our Taiwanese CPV 2a isolates and recent Asian isolates. CPV 2c was not observed in this study.",2014 Feb 25,"['Lin, Chao-Nan', 'Chien, Chi-Hsien', 'Chiou, Ming-Tang', 'Chueh, Ling-Ling', 'Hung, Meng-Yu', 'Hsu, Han-Siang']",Virol J,,,True
4509a768ab8962812dbdf4c610b6d741f84c8318,PMC,Beliefs and Knowledge about Vaccination against AH1N1pdm09 Infection and Uptake Factors among Chinese Parents,http://dx.doi.org/10.3390/ijerph110201989,PMC3945580,24534766,CC BY,"Vaccination against AH1N1pdm09 infection (human swine infection, HSI) is an effective measure of preventing pandemic infection, especially for high-risk groups like children between the ages of 6 months and 6 years. This study used a cross-sectional correlation design and aimed to identify predicting factors of parental acceptance of the HSI vaccine (HSIV) and uptake of the vaccination by their preschool-aged children in Hong Kong. A total of 250 parents were recruited from four randomly selected kindergartens. A self-administered questionnaire based on the health belief framework was used for data collection. The results showed that a number of factors significantly affected the tendency toward new vaccination uptake; these factors included parental age, HSI vaccination history of the children in their family, preferable price of the vaccine, perceived severity, perceived benefits, perceived barriers, and motivating factors for taking new vaccines. Using these factors, a logistic regression model with a high Nagelkerke R(2) of 0.63 was generated to explain vaccination acceptance. A strong correlation between parental acceptance of new vaccinations and the motivating factors of vaccination uptake was found, which indicates the importance of involving parents in policy implementation for any new vaccination schemes. Overall, in order to fight against pandemics and enhance vaccination acceptance, it is essential for the government to understand the above factors determining parental acceptance of new vaccinations for their preschool-aged children.",2014 Feb 14,"['Wu, Cynthia Sau Ting', 'Kwong, Enid Wai Yung', 'Wong, Ho Ting', 'Lo, Suet Hang', 'Wong, Anthony Siu Wo']",Int J Environ Res Public Health,,,True
3ab1d505d3521db73f63ef84163a41fa2f3dbdf6,PMC,Triple Immunoglobulin Gene Knockout Transchromosomic Cattle: Bovine Lambda Cluster Deletion and Its Effect on Fully Human Polyclonal Antibody Production,http://dx.doi.org/10.1371/journal.pone.0090383,PMC3946162,24603704,CC BY,"Towards the goal of producing fully human polyclonal antibodies (hpAbs or hIgGs) in transchromosomic (Tc) cattle, we previously reported that Tc cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin (Ig) heavy-chain (hIGH), kappa-chain (hIGK), and lambda-chain (hIGL) germline loci produced physiological levels of hIgGs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, were homozygously inactivated (bIGHM(−/−), bIGHML1(−/−); double knockouts or DKO). However, because endogenous bovine immunoglobulin light chain loci are still intact, the light chains are produced both from the hIGK and hIGL genomic loci on the HAC and from the endogenous bovine kappa-chain (bIGK) and lambda-chain (bIGL) genomic loci, resulting in the production of fully hIgGs (both Ig heavy-chains and light-chains are of human origin: hIgG/hIgκ or hIgG/hIgλ) and chimeric hIgGs (Ig heavy-chains are of human origin while the Ig light-chains are of bovine origin: hIgG/bIgκ or hIgG/bIgλ). To improve fully hIgG production in Tc cattle, we here report the deletion of the entire bIGL joining (J) and constant (C) gene cluster (bIGLJ1-IGLC1 to bIGLJ5-IGLC5) by employing Cre/loxP mediated site-specific chromosome recombination and the production of triple knockout (bIGHM(−/−), bIGHML1(−/−) and bIGL(−/−); TKO) Tc cattle. We further demonstrate that bIGL cluster deletion greatly improves fully hIgGs production in the sera of TKO Tc cattle, with 51.3% fully hIgGs (hIgG/hIgκ plus hIgG/hIgλ).",2014 Mar 6,"['Matsushita, Hiroaki', 'Sano, Akiko', 'Wu, Hua', 'Jiao, Jin-an', 'Kasinathan, Poothappillai', 'Sullivan, Eddie J.', 'Wang, Zhongde', 'Kuroiwa, Yoshimi']",PLoS One,,,True
e20aef0065c509346a868a73020a7ba5862e1cd5,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,True
40711ec13cb795b87708286783e253c429380e1f,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
3b0dd174adb4bc0f1dbdb74fba9c77c87761b31c,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
1066883cb4190d7564b147d36e4bf2fcb8189a81,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
6535b5a6a1907f1e51f373a3c727a2e0765d16ce,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
967f87ec152c33fd332b2ba5ea7c76a202951eb1,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
01cb25de5152563a0654eb672d932b5605a02eb6,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
9402e240e9b4d07e6b85174891e905d254078509,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
1532ab213d617b828362ffc2050097696995fd2f,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
852ae4dbba4756ff9d7e331eb12c1672fb7ebfed,PMC,Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm,http://dx.doi.org/10.1371/journal.ppat.1003971,PMC3946384,24603687,CC0,"Reassortment of influenza viral RNA (vRNA) segments in co-infected cells can lead to the emergence of viruses with pandemic potential. Replication of influenza vRNA occurs in the nucleus of infected cells, while progeny virions bud from the plasma membrane. However, the intracellular mechanics of vRNA assembly into progeny virions is not well understood. Here we used recent advances in microscopy to explore vRNA assembly and transport during a productive infection. We visualized four distinct vRNA segments within a single cell using fluorescent in situ hybridization (FISH) and observed that foci containing more than one vRNA segment were found at the external nuclear periphery, suggesting that vRNA segments are not exported to the cytoplasm individually. Although many cytoplasmic foci contain multiple vRNA segments, not all vRNA species are present in every focus, indicating that assembly of all eight vRNA segments does not occur prior to export from the nucleus. To extend the observations made in fixed cells, we used a virus that encodes GFP fused to the viral polymerase acidic (PA) protein (WSN PA-GFP) to explore the dynamics of vRNA assembly in live cells during a productive infection. Since WSN PA-GFP colocalizes with viral nucleoprotein and influenza vRNA segments, we used it as a surrogate for visualizing vRNA transport in 3D and at high speed by inverted selective-plane illumination microscopy. We observed cytoplasmic PA-GFP foci colocalizing and traveling together en route to the plasma membrane. Our data strongly support a model in which vRNA segments are exported from the nucleus as complexes that assemble en route to the plasma membrane through dynamic colocalization events in the cytoplasm.",2014 Mar 6,"['Lakdawala, Seema S.', 'Wu, Yicong', 'Wawrzusin, Peter', 'Kabat, Juraj', 'Broadbent, Andrew J.', 'Lamirande, Elaine W.', 'Fodor, Ervin', 'Altan-Bonnet, Nihal', 'Shroff, Hari', 'Subbarao, Kanta']",PLoS Pathog,,,False
62d7719c3402b89f11ccb6a158dc2812f10bc234,PMC,Depletion of Alveolar Macrophages Ameliorates Virus-Induced Disease following a Pulmonary Coronavirus Infection,http://dx.doi.org/10.1371/journal.pone.0090720,PMC3946553,24608125,CC BY,"Coronaviruses cause respiratory disease in humans that can range from mild to severe. However, the pathogenesis of pulmonary coronavirus infections is poorly understood. Mouse hepatitis virus type 1 (MHV-1) is a group 2 coronavirus capable of causing severe morbidity and mortality in highly susceptible C3H/HeJ mice. We have previously shown that both CD4 and CD8 T cells play a critical role in mediating MHV-1-induced disease. Here we evaluated the role of alveolar macrophages (AM) in modulating the adaptive immune response and subsequent disease. Depletion of AM using clodronate liposomes administered prior to MHV-1 infection was associated with a significant amelioration of MHV-1-induced morbidity and mortality. AM depletion resulted in a decreased number of virus-specific CD4 T cells in the lung airways. In addition, a significant increase in the frequency and total number of Tregs in the lung tissue and lung airways was observed following MHV-1 infection in mice depleted of AM. Our results indicate that AM play a critical role in modulating MHV-1-induced morbidity and mortality.",2014 Mar 7,"['Hartwig, Stacey M.', 'Holman, Kaitlyn M.', 'Varga, Steven M.']",PLoS One,,,True
5c4dfdf8ee6230324845b917be55c47d1e991f2c,PMC,hCLE/C14orf166 Associates with DDX1-HSPC117-FAM98B in a Novel Transcription-Dependent Shuttling RNA-Transporting Complex,http://dx.doi.org/10.1371/journal.pone.0090957,PMC3946611,24608264,CC BY,"hCLE/C14orf166 is a nuclear and cytoplasmic protein that interacts with the RNAP II, modulates nuclear RNA metabolism and is present in cytoplasmic RNA granules involved in localized translation. Here we have studied whether hCLE shares common interactors in the nucleus and the cytosol, which could shed light on its participation in the sequential phases of RNA metabolism. Nuclear and cytoplasmic purified hCLE-associated factors were identified and proteins involved in mRNA metabolism, motor-related proteins, cytoskeletal and translation-related factors were found. Purified hCLE complexes also contain RNAs and as expected some hCLE-interacting proteins (DDX1, HSPC117, FAM98B) were found both in the nucleus and the cytoplasm. Moreover, endogenous hCLE fractionates in protein complexes together with DDX1, HSPC117 and FAM98B and silencing of hCLE down-regulates their nuclear and cytosolic accumulation levels. Using a photoactivatable hCLE-GFP protein, nuclear import and export of hCLE was observed indicating that hCLE is a shuttling protein. Interestingly, hCLE nuclear import required active transcription, as did the import of DDX1, HSPC117 and FAM98B proteins. The data indicate that hCLE probably as a complex with DDX1, HSPC117 and FAM98B shuttles between the nucleus and the cytoplasm transporting RNAs suggesting that this complex has a prominent role on nuclear and cytoplasmic RNA fate.",2014 Mar 7,"['Pérez-González, Alicia', 'Pazo, Alejandra', 'Navajas, Rosana', 'Ciordia, Sergio', 'Rodriguez-Frandsen, Ariel', 'Nieto, Amelia']",PLoS One,,,True
6ec1c2c2244a8d8f5959fad54ba3b7923e72e971,PMC,Intentions to Perform Non-Pharmaceutical Protective Behaviors during Influenza Outbreaks in Sweden: A Cross-Sectional Study following a Mass Vaccination Campaign,http://dx.doi.org/10.1371/journal.pone.0091060,PMC3946657,24608557,CC BY,"Failure to incorporate the beliefs and attitudes of the public into theoretical models of preparedness has been identified as a weakness in strategies to mitigate infectious disease outbreaks. We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. The interviewees were asked to make their appraisals for two scenarios: a) an influenza with low case fatality and mild lifestyle impact; b) severe influenza with high case fatality and serious disturbances of societal functions. Every second respondent (50.0%) reported high trust in official information about influenza. The proportion that reported intentions to take deliberate actions to improve personal hygiene during outbreaks ranged between 45–85%, while less than 25% said that they intended to increase social distancing. Multiple logistic regression models with coping appraisal as the explanatory factor most frequently contributing to the explanation of the variance in intentions showed strong discriminatory performance for staying home while not ill (mild outbreaks: Area under the curve [AUC] 0.85 (95% confidence interval 0.82;0.89), severe outbreaks AUC 0.82 (95% CI 0.77;0.85)) and acceptable performance with regard to avoiding public transportation (AUC 0.78 (0.74;0.82), AUC 0.77 (0.72;0.82)), using handwash products (AUC 0.70 (0.65;0.75), AUC 0.76 (0.71;0.80)), and frequently washing hands (AUC 0.71 (0.66;0.76), AUC 0.75 (0.71;0.80)). We conclude that coping appraisal was the explanatory factor most frequently included in statistical models explaining self-reported intentions to carry out non-pharmaceutical health actions in the Swedish outlined context, and that variations in threat appraisal played a smaller role in these models despite scientific uncertainties surrounding a recent mass vaccination campaign.",2014 Mar 7,"['Timpka, Toomas', 'Spreco, Armin', 'Gursky, Elin', 'Eriksson, Olle', 'Dahlström, Örjan', 'Strömgren, Magnus', 'Ekberg, Joakim', 'Pilemalm, Sofie', 'Karlsson, David', 'Hinkula, Jorma', 'Holm, Einar']",PLoS One,,,True
2318d71622cd266fdbd9a9d80f25e689ff6f61ae,PMC,Detection of Viral Proteins in Human Cells Lines by Xeno-Proteomics: Elimination of the Last Valid Excuse for Not Testing Every Cellular Proteome Dataset for Viral Proteins,http://dx.doi.org/10.1371/journal.pone.0091433,PMC3950186,24618588,CC BY,"Cell cultures used routinely in proteomic experiments may contain proteins from other species because of infection, transfection or just contamination. Since infection or contamination may affect the results of a biological experiment, it is important to test the samples for the presence of “alien” proteins. Usually cells are tested only for the most common infections, and most of the existing tests are targeting specific contaminations. Here we describe a three-step procedure for reliable untargeted detection of viral proteins using proteomics data, and recommend this or similar procedure to be applied to every proteomics dataset submitted for publication.",2014 Mar 11,"['Chernobrovkin, Alexey L.', 'Zubarev, Roman A.']",PLoS One,,,True
da9d1b5baf44c1abc7fa6b9e3f99f2de27f1a7c4,PMC,Detection of Viral Proteins in Human Cells Lines by Xeno-Proteomics: Elimination of the Last Valid Excuse for Not Testing Every Cellular Proteome Dataset for Viral Proteins,http://dx.doi.org/10.1371/journal.pone.0091433,PMC3950186,24618588,CC BY,"Cell cultures used routinely in proteomic experiments may contain proteins from other species because of infection, transfection or just contamination. Since infection or contamination may affect the results of a biological experiment, it is important to test the samples for the presence of “alien” proteins. Usually cells are tested only for the most common infections, and most of the existing tests are targeting specific contaminations. Here we describe a three-step procedure for reliable untargeted detection of viral proteins using proteomics data, and recommend this or similar procedure to be applied to every proteomics dataset submitted for publication.",2014 Mar 11,"['Chernobrovkin, Alexey L.', 'Zubarev, Roman A.']",PLoS One,,,False
c0617473da97a9dd36b02d46fe80b144f2138f0a,PMC,Cellular trafficking determines the exon skipping activity of Pip6a-PMO in mdx skeletal and cardiac muscle cells,http://dx.doi.org/10.1093/nar/gkt1220,PMC3950666,24366877,CC BY,"Cell-penetrating peptide-mediated delivery of phosphorodiamidate morpholino oligomers (PMOs) has shown great promise for exon-skipping therapy of Duchenne Muscular Dystrophy (DMD). Pip6a-PMO, a recently developed conjugate, is particularly efficient in a murine DMD model, although mechanisms responsible for its increased biological activity have not been studied. Here, we evaluate the cellular trafficking and the biological activity of Pip6a-PMO in skeletal muscle cells and primary cardiomyocytes. Our results indicate that Pip6a-PMO is taken up in the skeletal muscle cells by an energy- and caveolae-mediated endocytosis. Interestingly, its cellular distribution is different in undifferentiated and differentiated skeletal muscle cells (vesicular versus nuclear). Likewise, Pip6a-PMO mainly accumulates in cytoplasmic vesicles in primary cardiomyocytes, in which clathrin-mediated endocytosis seems to be the pre-dominant uptake pathway. These differences in cellular trafficking correspond well with the exon-skipping data, with higher activity in myotubes than in myoblasts or cardiomyocytes. These differences in cellular trafficking thus provide a possible mechanistic explanation for the variations in exon-skipping activity and restoration of dystrophin protein in heart muscle compared with skeletal muscle tissues in DMD models. Overall, Pip6a-PMO appears as the most efficient conjugate to date (low nanomolar EC(50)), even if limitations remain from endosomal escape.",2014 Mar 22,"['Lehto, Taavi', 'Castillo Alvarez, Alejandra', 'Gauck, Sarah', 'Gait, Michael J.', 'Coursindel, Thibault', 'Wood, Matthew J. A.', 'Lebleu, Bernard', 'Boisguerin, Prisca']",Nucleic Acids Res,,,True
b1f90c0a862d8dc3485d61deb8c87c0b53b798b8,PMC,"Hantaan Virus Infection Induces CXCL10 Expression through TLR3, RIG-I, and MDA-5 Pathways Correlated with the Disease Severity",http://dx.doi.org/10.1155/2014/697837,PMC3950924,24701034,CC BY,"Hantaan virus (HTNV) is a major agent causing hemorrhagic fever with renal syndrome (HFRS). Although the pathogenesis of HFRS is unclear, some reports have suggested that the abundant production of proinflammatory cytokines and uncontrolled inflammatory responses may contribute to the development of HFRS. CXCL10 is one of these cytokines and is found to be involved in the pathogenesis of many virus infectious diseases. However, the role of CXCL10 in the pathogenesis of HFRS and the molecular regulation mechanism of CXCL10 in HTNV infection remain unknown. In this study, we report that CXCL10 expresses highly in the HFRS patients' sera and the elevated CXCL10 is positively correlated with the severity of HFRS. We find that HTNV, a single-strand RNA virus, can act as a double-strand RNA to activate the TLR3, RIG-I, and MDA-5 signaling pathways. Through the downstream transcription factors of these pathways, NF-κB and IRF7, which bind directly to the CXCL10's promoter, the expression of CXCL10 is increased. Our results may help to better understand the role of CXCL10 in the development of HFRS and may provide some novel insights into the immune response of HTNV infection.",2014 Feb 23,"['Zhang, Yusi', 'Liu, Bei', 'Ma, Ying', 'Yi, Jing', 'Zhang, Chunmei', 'Zhang, Yun', 'Xu, Zhuwei', 'Wang, Jiuping', 'Yang, Kun', 'Yang, Angang', 'Zhuang, Ran', 'Jin, Boquan']",Mediators Inflamm,,,True
f5ad2323eb387f6e271e2842bb2cc4a33504fde3,PMC,In Vitro Antiviral Activity of Circular Triple Helix Forming Oligonucleotide RNA towards Feline Infectious Peritonitis Virus Replication,http://dx.doi.org/10.1155/2014/654712,PMC3950953,24707494,CC BY,"Feline Infectious Peritonitis (FIP) is a severe fatal immune-augmented disease in cat population. It is caused by FIP virus (FIPV), a virulent mutant strain of Feline Enteric Coronavirus (FECV). Current treatments and prophylactics are not effective. The in vitro antiviral properties of five circular Triple-Helix Forming Oligonucleotide (TFO) RNAs (TFO1 to TFO5), which target the different regions of virulent feline coronavirus (FCoV) strain FIPV WSU 79-1146 genome, were tested in FIPV-infected Crandell-Rees Feline Kidney (CRFK) cells. RT-qPCR results showed that the circular TFO RNAs, except TFO2, inhibit FIPV replication, where the viral genome copy numbers decreased significantly by 5-fold log(10) from 10(14) in the virus-inoculated cells to 10(9) in the circular TFO RNAs-transfected cells. Furthermore, the binding of the circular TFO RNA with the targeted viral genome segment was also confirmed using electrophoretic mobility shift assay. The strength of binding kinetics between the TFO RNAs and their target regions was demonstrated by NanoITC assay. In conclusion, the circular TFOs have the potential to be further developed as antiviral agents against FIPV infection.",2014 Feb 20,"['Choong, Oi Kuan', 'Mehrbod, Parvaneh', 'Tejo, Bimo Ario', 'Omar, Abdul Rahman']",Biomed Res Int,,,True
772e7c8efc8fed6e7c27602dc255fd97f2f55a7e,PMC,China Tuberculosis Policy at Crucial Crossroads: Comparing the Practice of Different Hospital and Tuberculosis Control Collaboration Models Using Survey Data,http://dx.doi.org/10.1371/journal.pone.0090596,PMC3951218,24621996,CC BY,"BACKGROUND: Currently three hospital and tuberculosis (TB) collaboration models exist in China: the dispensary model where TB has to be diagnosed and treated in TB dispensaries, the specialist model where TB specialist hospital also treat TB patients, and the integrated model where TB diagnosis and treatment is integrated into a general hospital. The study compared effects of the three models through exploring patient experience in TB diagnosis and treatment. METHODS: We selected two sites in each model of TB service in four provinces of China. In each site, 50 patients were selected from TB patient registries for a structured questionnaire survey, with a total of 293 patients recruited. All participants were newly registered uncomplicated TB cases without any major complications or resistance to first-line anti-TB drugs, and having successfully completed treatment. Diagnostic and treatment procedures were reviewed from medical charts of the surveyed patients to compare with national guidelines. RESULTS: Specialist sites had the highest patient expenditure, hospitalization rates and mostly used second-line anti-TB drugs, while the integrated model reported the opposite. The median health expenditure was USD 1,499 for the specialist sites and USD 306 for the integrated sites, with 83% and 15% patients respectively having unnecessary hospitalization. 74% of the specialist sites and 19% of the integrated sites used second-line anti-TB drugs. Mixed results were identified in the two dispensary sites. One site had median health expenditure of USD 138 with 12% of patients hospitalized, while the other had USD 912 and 65% respectively. CONCLUSION: The study observed prohibitive financial expenditure and a high level of deviation from national guidelines in all sites, which may be related to the profit-seeking behavior of public hospitals. The study supports the integrated model as the better policy option for future TB health reform in China.",2014 Mar 12,"['Wei, Xiaolin', 'Zou, Guanyang', 'Walley, John', 'Yin, Jia', 'Lonnroth, Knut', 'Uplekar, Mukund', 'Wang, Weibing', 'Sun, Qiang']",PLoS One,,,True
832fab67c299fb2682948d33858e58a5db71e6f8,PMC,A Novel Vaccine against Crimean-Congo Haemorrhagic Fever Protects 100% of Animals against Lethal Challenge in a Mouse Model,http://dx.doi.org/10.1371/journal.pone.0091516,PMC3951450,24621656,CC BY,"Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15–70% of reported cases are fatal. There is no approved vaccine available, and preclinical protection in vivo by an experimental vaccine has not been demonstrated previously. In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus glycoproteins. Cellular and humoral immunogenicity was confirmed in two mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. This vaccine protected all recipient animals from lethal disease in a challenge model adapted to represent infection via a tick bite. Histopathology and viral load analysis of protected animals confirmed that they had been exposed to challenge virus, even though they did not exhibit clinical signs. This is the first demonstration of efficacy of a CCHF vaccine.",2014 Mar 12,"['Buttigieg, Karen R.', 'Dowall, Stuart D.', 'Findlay-Wilson, Stephen', 'Miloszewska, Aleksandra', 'Rayner, Emma', 'Hewson, Roger', 'Carroll, Miles W.']",PLoS One,,,True
b4b8196a56fe00d653d288226f12952824c5b7cc,PMC,Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned,http://dx.doi.org/10.3389/fncel.2014.00073,PMC3952085,24659953,CC BY,"Although astrogliosis and microglia activation are characteristic features of multiple sclerosis (MS) and other central nervous system (CNS) lesions the exact functions of these events are not fully understood. Animal models help to understand the complex interplay between the different cell types of the CNS and uncover general mechanisms of damage and repair of myelin sheaths. The so called cuprizone model is a toxic model of demyelination in the CNS white and gray matter, which lacks an autoimmune component. Cuprizone induces apoptosis of mature oligodendrocytes that leads to a robust demyelination and profound activation of both astrocytes and microglia with regional heterogeneity between different white and gray matter regions. Although not suitable to study autoimmune mediated demyelination, this model is extremely helpful to elucidate basic cellular and molecular mechanisms during de- and particularly remyelination independently of interactions with peripheral immune cells. Phagocytosis and removal of damaged myelin seems to be one of the major roles of microglia in this model and it is well known that removal of myelin debris is a prerequisite of successful remyelination. Furthermore, microglia provide several signals that support remyelination. The role of astrocytes during de- and remyelination is not well defined. Both supportive and destructive functions have been suggested. Using the cuprizone model we could demonstrate that there is an important crosstalk between astrocytes and microglia. In this review we focus on the role of glial reactions and interaction in the cuprizone model. Advantages and limitations of as well as its potential therapeutic relevance for the human disease MS are critically discussed in comparison to other animal models.",2014 Mar 13,"['Gudi, Viktoria', 'Gingele, Stefan', 'Skripuletz, Thomas', 'Stangel, Martin']",Front Cell Neurosci,,,True
879b0904d411e88c1be90f0660e7bb4377ae29d8,PMC,Porcine epidemic diarrhea virus (PEDV) co-infection induced chlamydial persistence/stress does not require viral replication,http://dx.doi.org/10.3389/fcimb.2014.00020,PMC3952398,24660163,CC BY,"Chlamydiae may exist at the site of infection in an alternative replicative form, called the aberrant body (AB). ABs are produced during a viable but non-infectious developmental state termed “persistence” or “chlamydial stress.” As persistent/stressed chlamydiae: (i) may contribute to chronic inflammation observed in diseases like trachoma; and (ii) are more resistant to current anti-chlamydial drugs of choice, it is critical to better understand this developmental stage. We previously demonstrated that porcine epidemic diarrhea virus (PEDV) co-infection induced Chlamydia pecorum persistence/stress in culture. One critical characteristic of persistence/stress is that the chlamydiae remain viable and can reenter the normal developmental cycle when the stressor is removed. Thus, we hypothesized that PEDV-induced persistence would be reversible if viral replication was inhibited. Therefore, we performed time course experiments in which Vero cells were C. pecorum/PEDV infected in the presence of cycloheximide (CHX), which inhibits viral but not chlamydial protein synthesis. CHX-exposure inhibited PEDV replication, but did not inhibit induction of C. pecorum persistence at 24 h post-PEDV infection, as indicated by AB formation and reduced production of infectious EBs. Interestingly, production of infectious EBs resumed when CHX-exposed, co-infected cells were incubated 48–72 h post-PEDV co-infection. These data demonstrate that PEDV co-infection-induced chlamydial persistence/stress is reversible and suggest that this induction (i) does not require viral replication in host cells; and (ii) does not require de novo host or viral protein synthesis. These data also suggest that viral binding and/or entry may be required for this effect. Because the PEDV host cell receptor (CD13 or aminopeptidase N) stimulates cellular signaling pathways in the absence of PEDV infection, we suspect that PEDV co-infection might alter CD13 function and induce the chlamydiae to enter the persistent state.",2014 Mar 13,"['Schoborg, Robert V.', 'Borel, Nicole']",Front Cell Infect Microbiol,,,True
be45cd588caaa0d8e5cdcd0cb7a1a59ccfc85d51,PMC,Enhancement of accuracy and efficiency for RNA secondary structure prediction by sequence segmentation and MapReduce,http://dx.doi.org/10.1186/1472-6807-13-S1-S3,PMC3952952,24564983,CC BY,"BACKGROUND: Ribonucleic acid (RNA) molecules play important roles in many biological processes including gene expression and regulation. Their secondary structures are crucial for the RNA functionality, and the prediction of the secondary structures is widely studied. Our previous research shows that cutting long sequences into shorter chunks, predicting secondary structures of the chunks independently using thermodynamic methods, and reconstructing the entire secondary structure from the predicted chunk structures can yield better accuracy than predicting the secondary structure using the RNA sequence as a whole. The chunking, prediction, and reconstruction processes can use different methods and parameters, some of which produce more accurate predictions than others. In this paper, we study the prediction accuracy and efficiency of three different chunking methods using seven popular secondary structure prediction programs that apply to two datasets of RNA with known secondary structures, which include both pseudoknotted and non-pseudoknotted sequences, as well as a family of viral genome RNAs whose structures have not been predicted before. Our modularized MapReduce framework based on Hadoop allows us to study the problem in a parallel and robust environment. RESULTS: On average, the maximum accuracy retention values are larger than one for our chunking methods and the seven prediction programs over 50 non-pseudoknotted sequences, meaning that the secondary structure predicted using chunking is more similar to the real structure than the secondary structure predicted by using the whole sequence. We observe similar results for the 23 pseudoknotted sequences, except for the NUPACK program using the centered chunking method. The performance analysis for 14 long RNA sequences from the Nodaviridae virus family outlines how the coarse-grained mapping of chunking and predictions in the MapReduce framework exhibits shorter turnaround times for short RNA sequences. However, as the lengths of the RNA sequences increase, the fine-grained mapping can surpass the coarse-grained mapping in performance. CONCLUSIONS: By using our MapReduce framework together with statistical analysis on the accuracy retention results, we observe how the inversion-based chunking methods can outperform predictions using the whole sequence. Our chunk-based approach also enables us to predict secondary structures for very long RNA sequences, which is not feasible with traditional methods alone.",2013 Nov 8,"['Zhang, Boyu', 'Yehdego, Daniel T', 'Johnson, Kyle L', 'Leung, Ming-Ying', 'Taufer, Michela']",BMC Struct Biol,,,True
5da136317f5b97ed8371d5121d8828f1c9a5372d,PMC,Congenital Malaria in China,http://dx.doi.org/10.1371/journal.pntd.0002622,PMC3953009,24626148,CC BY,"ABSTRACT: BACKGROUND: Congenital malaria, in which infants are directly infected with malaria parasites from their mother prior to or during birth, is a potentially life-threatening condition that occurs at relatively low rates in malaria-endemic regions. It is recognized as a serious problem in Plasmodium falciparum–endemic sub-Saharan Africa, where recent data suggests that it is more common than previously believed. In such regions where malaria transmission is high, neonates may be protected from disease caused by congenital malaria through the transfer of maternal antibodies against the parasite. However, in low P. vivax–endemic regions, immunity to vivax malaria is low; thus, there is the likelihood that congenital vivax malaria poses a more significant threat to newborn health. Malaria had previously been a major parasitic disease in China, and congenital malaria case reports in Chinese offer valuable information for understanding the risks posed by congenital malaria to neonatal health. As most of the literature documenting congenital malaria cases in China are written in Chinese and therefore are not easily accessible to the global malaria research community, we have undertaken an extensive review of the Chinese literature on this subject. METHODS/PRINCIPAL FINDINGS: Here, we reviewed congenital malaria cases from three major searchable Chinese journal databases, concentrating on data from 1915 through 2011. Following extensive screening, a total of 104 cases of congenital malaria were identified. These cases were distributed mainly in the eastern, central, and southern regions of China, as well as in the low-lying region of southwest China. The dominant species was P. vivax (92.50%), reflecting the malaria parasite species distribution in China. The leading clinical presentation was fever, and other clinical presentations were anaemia, jaundice, paleness, diarrhoea, vomiting, and general weakness. With the exception of two cases, all patients were cured with antimalarial drugs such as chloroquine, quinine, artemether, and artesunate. CONCLUSIONS: The symptoms of congenital malaria vary significantly between cases, so clear and early diagnosis is difficult. We suggest that active surveillance might be necessary for neonates born to mothers with a history of malaria.",2014 Mar 13,"['Tao, Zhi-yong', 'Fang, Qiang', 'Liu, Xue', 'Culleton, Richard', 'Tao, Li', 'Xia, Hui', 'Gao, Qi']",PLoS Negl Trop Dis,,,True
0f6b1645fdc27b32ae9fdb4f99dbbb30eb1dfd7f,PMC,Dengue Virus Type 2 (DENV2)-Induced Oxidative Responses in Monocytes from Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient and G6PD Normal Subjects,http://dx.doi.org/10.1371/journal.pntd.0002711,PMC3953068,24625456,CC BY,"BACKGROUND: Dengue virus is endemic in peninsular Malaysia. The clinical manifestations vary depending on the incubation period of the virus as well as the immunity of the patients. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is prevalent in Malaysia where the incidence is 3.2%. It has been noted that some G6PD-deficient individuals suffer from more severe clinical presentation of dengue infection. In this study, we aim to investigate the oxidative responses of DENV2-infected monocytes from G6PD-deficient individuals. METHODOLOGY: Monocytes from G6PD-deficient individuals were infected with DENV2 and infection rate, levels of oxidative species, nitric oxide (NO), superoxide anions (O(2) (−)), and oxidative stress were determined and compared with normal controls. PRINCIPAL FINDINGS: Monocytes from G6PD-deficient individuals exhibited significantly higher infection rates compared to normal controls. In an effort to explain the reason for this enhanced susceptibility, we investigated the production of NO and O(2) (−) in the monocytes of individuals with G6PD deficiency compared with normal controls. We found that levels of NO and O(2) (−) were significantly lower in the DENV-infected monocytes from G6PD-deficient individuals compared with normal controls. Furthermore, the overall oxidative stress in DENV-infected monocytes from G6PD-deficient individuals was significantly higher when compared to normal controls. Correlation studies between DENV-infected cells and oxidative state of monocytes further confirmed these findings. CONCLUSIONS/SIGNIFICANCE: Altered redox state of DENV-infected monocytes from G6PD-deficient individuals appears to augment viral replication in these cells. DENV-infected G6PD-deficient individuals may contain higher viral titers, which may be significant in enhanced virus transmission. Furthermore, granulocyte dysfunction and higher viral loads in G6PD-deificient individuals may result in severe form of dengue infection.",2014 Mar 13,"['Al-alimi, Abdullah Ahmed', 'Ali, Syed A.', 'Al-Hassan, Faisal Muti', 'Idris, Fauziah Mohd', 'Teow, Sin-Yeang', 'Mohd Yusoff, Narazah']",PLoS Negl Trop Dis,,,True
d964ce1c8dd79290032b1b70d511f256b805e558,PMC,Adaptive Gene Amplification As an Intermediate Step in the Expansion of Virus Host Range,http://dx.doi.org/10.1371/journal.ppat.1004002,PMC3953438,24626510,CC BY,"The majority of recently emerging infectious diseases in humans is due to cross-species pathogen transmissions from animals. To establish a productive infection in new host species, viruses must overcome barriers to replication mediated by diverse and rapidly evolving host restriction factors such as protein kinase R (PKR). Many viral antagonists of these restriction factors are species specific. For example, the rhesus cytomegalovirus PKR antagonist, RhTRS1, inhibits PKR in some African green monkey (AGM) cells, but does not inhibit human or rhesus macaque PKR. To model the evolutionary changes necessary for cross-species transmission, we generated a recombinant vaccinia virus that expresses RhTRS1 in a strain that lacks PKR inhibitors E3L and K3L (VVΔEΔK+RhTRS1). Serially passaging VVΔEΔK+RhTRS1 in minimally-permissive AGM cells increased viral replication 10- to 100-fold. Notably, adaptation in these AGM cells also improved virus replication 1000- to 10,000-fold in human and rhesus cells. Genetic analyses including deep sequencing revealed amplification of the rhtrs1 locus in the adapted viruses. Supplying additional rhtrs1 in trans confirmed that amplification alone was sufficient to improve VVΔEΔK+RhTRS1 replication. Viruses with amplified rhtrs1 completely blocked AGM PKR, but only partially blocked human PKR, consistent with the replication properties of these viruses in AGM and human cells. Finally, in contrast to AGM-adapted viruses, which could be serially propagated in human cells, VVΔEΔK+RhTRS1 yielded no progeny virus after only three passages in human cells. Thus, rhtrs1 amplification in a minimally permissive intermediate host was a necessary step, enabling expansion of the virus range to previously nonpermissive hosts. These data support the hypothesis that amplification of a weak viral antagonist may be a general evolutionary mechanism to permit replication in otherwise resistant host species, providing a molecular foothold that could enable further adaptations necessary for efficient replication in the new host.",2014 Mar 13,"['Brennan, Greg', 'Kitzman, Jacob O.', 'Rothenburg, Stefan', 'Shendure, Jay', 'Geballe, Adam P.']",PLoS Pathog,,,True
8a096b3f838ccc2fab01f191ea2aacd2005f3f68,PMC,Epidemics in Partially Overlapped Multiplex Networks,http://dx.doi.org/10.1371/journal.pone.0092200,PMC3954885,24632709,CC BY,"Many real networks exhibit a layered structure in which links in each layer reflect the function of nodes on different environments. These multiple types of links are usually represented by a multiplex network in which each layer has a different topology. In real-world networks, however, not all nodes are present on every layer. To generate a more realistic scenario, we use a generalized multiplex network and assume that only a fraction [Image: see text] of the nodes are shared by the layers. We develop a theoretical framework for a branching process to describe the spread of an epidemic on these partially overlapped multiplex networks. This allows us to obtain the fraction of infected individuals as a function of the effective probability that the disease will be transmitted [Image: see text]. We also theoretically determine the dependence of the epidemic threshold on the fraction [Image: see text] of shared nodes in a system composed of two layers. We find that in the limit of [Image: see text] the threshold is dominated by the layer with the smaller isolated threshold. Although a system of two completely isolated networks is nearly indistinguishable from a system of two networks that share just a few nodes, we find that the presence of these few shared nodes causes the epidemic threshold of the isolated network with the lower propagating capacity to change discontinuously and to acquire the threshold of the other network.",2014 Mar 14,"['Buono, Camila', 'Alvarez-Zuzek, Lucila G.', 'Macri, Pablo A.', 'Braunstein, Lidia A.']",PLoS One,,,True
f7735a5236aeba514810bd4538357cb4f4e09fce,PMC,Differential Host Cell Gene Expression and Regulation of Cell Cycle Progression by Nonstructural Protein 11 of Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1155/2014/430508,PMC3955671,24719865,CC BY,"Nonstructural protein 11 (nsp11) of porcine reproductive and respiratory syndrome virus (PRRSV) is a viral endoribonuclease with an unknown function. The regulation of cellular gene expression by nsp11 was examined by RNA microarrays using MARC-nsp11 cells constitutively expressing nsp11. In these cells, the interferon-β, interferon regulatory factor 3, and nuclear factor-κB activities were suppressed compared to those of parental cells, suggesting that nsp11 might serve as a viral interferon antagonist. Differential cellular transcriptome was examined using Affymetrix exon chips representing 28,536 transcripts, and after statistical analyses 66 cellular genes were shown to be upregulated and 104 genes were downregulated by nsp11. These genes were grouped into 5 major signaling pathways according to their functional relations: histone-related, cell cycle and DNA replication, mitogen activated protein kinase signaling, complement, and ubiquitin-proteasome pathways. Of these, the modulation of cell cycle by nsp11 was further investigated since many of the regulated genes fell in this particular pathway. Flow cytometry showed that nsp11 caused the delay of cell cycle progression at the S phase and the BrdU staining confirmed the cell cycle arrest in nsp11-expressing cells. The study provides insights into the understanding of specific cellular responses to nsp11 during PRRSV infection.",2014 Feb 26,"['Sun, Yan', 'Li, Dong', 'Giri, Sumanprava', 'Prasanth, Supriya G.', 'Yoo, Dongwan']",Biomed Res Int,,,True
de925d6c5bc669b0ada19aedaf299dfaed7445ad,PMC,Migration and health in Southern Africa: 100 years and still circulating,http://dx.doi.org/10.1080/21642850.2013.866898,PMC3956074,24653964,CC BY,"Migration has deep historical roots in South and Southern Africa and to this day continues to be highly prevalent and a major factor shaping South African society and health. In this paper we examine the role of migration in the spread of two diseases nearly 100 years apart: tuberculosis following the discovery of gold in 1886 and HIV in the early 1990s. Both cases demonstrate the critical role played by human migration in the transmission and subsequent dissemination of these diseases to rural areas. In both cases, migration acts to assemble in one high-risk environment thousands of young men highly susceptible to new diseases. With poor living and working conditions, these migration destinations act as hot-spots for disease transmission. Migration of workers back to rural areas then serves as a highly efficient means of disseminating these diseases to rural populations. We conclude by raising some more recent questions examining the current role of migration in Southern Africa.",2014 Jan 1,"['Lurie, Mark N.', 'Williams, Brian G.']",Health Psychol Behav Med,,,True
dcb83fc0259abca0186d62b0b1d32eaf8607fcfc,PMC,Gene Silencing of SOCS3 by siRNA Intranasal Delivery Inhibits Asthma Phenotype in Mice,http://dx.doi.org/10.1371/journal.pone.0091996,PMC3956882,24637581,CC BY,"Suppresors of cytokine signaling (SOCS) proteins regulate cytokine responses and control immune balance. Several studies have confirmed that SOCS3 is increased in asthmatic patients, and SOCS3 expression is correlated with disease severity. The objective of this study was to evaluate if delivering of SOCS3 short interfering RNA (siRNA) intranasally in lungs could be a good therapeutic approach in an asthma chronic mouse model. Our results showed that intranasal treatment with SOCS3-siRNA led to an improvement in the eosinophil count and the normalization of hyperresponsiveness to methacholine. Concomitantly, this treatment resulted in an improvement in mucus secretion, a reduction in lung collagen, which are prominent features of airway remodeling. The mechanism implies JAK/STAT and RhoA/Rho-kinase signaling pathway, because we found a decreasing in STAT3 phosphorylation status and down regulation of RhoA/Rho-kinase protein expression. These results might lead to a new therapy for the treatment of chronic asthma.",2014 Mar 17,"[None, 'Mazzeo, Carla', 'Gámez, Cristina', 'Rodriguez Marco, Ainara', 'de Zulueta, Ana', 'Sanz, Veronica', 'Bilbao, Izaskun', 'Ruiz-Cabello, Jesús', 'Zubeldia, Jose M.', 'del Pozo, Victoria']",PLoS One,,,True
3159f6ba739648bbaa0b8b7eb498924a8d21cf8e,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,True
00378829b1df524d9f72cdad968dc635c614fa41,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
9a306ee64f21422e00a4b55bd1cec04d2d35a836,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
b7f569585aafded757463cd95eeb68534001841f,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
449ffbcc271a7f0606d6d6e1db69d135e82cebff,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
ea5e91fad311e440b03ace589789841ecb0d3d8d,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
fd314c9703b75474ea7a9cd80acd8edb028eda3d,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
7489c191e0bb82790ad2be5b708e0f49e0ba0332,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
5d5256f8f520d9752d5fef8425df87d7a953cde0,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
20a618f5cb2d18add9852731a45e81d2404f346b,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
517c73d7a87c11b3a643f609c9ceee95b5432581,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
7c608e69084d51e22aba905364bc88ff2819698f,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
3e77bba0df6bcecc06f68cb14627737ed8f747d3,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
6523295fccf833aa2e20ecf80196ea7fbd82b043,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
5753df8ed90cfb059e39566ad1271587df4ad31d,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
8a729774a87e5a4a908a85e01b24ca6882e7c2f8,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
87258f75b4634f185e7062cae7628e27f83a6dcc,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
ae7e947ef8f28c4a5f1ee201cf0c2d6cd54a40d8,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
1bc2878023734630f4bfdf86bf62b0bdeebc7d7b,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
59013a7b62d641a9e14cabe90fcda41a52870772,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
4126632a4e57a806d8da05023850ba8755cf802f,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
f7a1f8ff3552ac192d882ad7ef31d46c21ca1e32,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,True
990153e74de3d5bc506c686afb5dbf037cfa5d6b,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
810ff7a21410bfe51bc95f54e9bfdb922d9ef848,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
fb4c3d10a9ea514f135f1fdbc5b535bd7955d888,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
3282216c38dff96f0fa23f520317ad7572fa1da2,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
1d960a741888ae2ee9c8a7ea154c651de9cbd272,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
11da1c0cfae7699891514093f0695df560e4fc99,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
fc86da0d534cd666f77d946c63a8cea739111283,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
48c4de8366001c46339033536193b44103ee7f96,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
ac2a2ff57637dadf2e51cc82b4ef561765b715c9,PMC,Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury,http://dx.doi.org/10.1002/emmm.201303236,PMC3958312,24480543,CC BY,"Type 1 interferons (IFN) protect the host against viruses by engaging a cognate receptor (consisting of IFNAR1/IFNAR2 chains) and inducing downstream signaling and gene expression. However, inflammatory stimuli can trigger IFNAR1 ubiquitination and downregulation thereby attenuating IFN effects in vitro. The significance of this paradoxical regulation is unknown. Presented here results demonstrate that inability to stimulate IFNAR1 ubiquitination in the Ifnar1(SA) knock-in mice renders them highly susceptible to numerous inflammatory syndromes including acute and chronic pancreatitis, and autoimmune and toxic hepatitis. Ifnar1(SA) mice (or their bone marrow-receiving wild type animals) display persistent immune infiltration of inflamed tissues, extensive damage and gravely inadequate tissue regeneration. Pharmacologic stimulation of IFNAR1 ubiquitination is protective against from toxic hepatitis and fulminant generalized inflammation in wild type but not Ifnar1(SA) mice. These results suggest that endogenous mechanisms that trigger IFNAR1 ubiquitination for limiting the inflammation-induced tissue damage can be purposely mimicked for therapeutic benefits. Subject Categories Immunology; Digestive System",2014 Mar 31,"['Bhattacharya, Sabyasachi', 'Katlinski, Kanstantsin V', 'Reichert, Maximilian', 'Takano, Shigetsugu', 'Brice, Angela', 'Zhao, Bin', 'Yu, Qiujing', 'Zheng, Hui', 'Carbone, Christopher J', 'Katlinskaya, Yuliya V', 'Leu, N Adrian', 'McCorkell, Kelly A', 'Srinivasan, Satish', 'Girondo, Melanie', 'Rui, Hallgeir', 'May, Michael J', 'Avadhani, Narayan G', 'Rustgi, Anil K', 'Fuchs, Serge Y']",EMBO Mol Med,,,False
5fa8a1eb8fab8c225ab28402700a6c3aa950f2d6,PMC,DBatVir: the database of bat-associated viruses,http://dx.doi.org/10.1093/database/bau021,PMC3958617,24647629,CC BY,"Emerging infectious diseases remain a significant threat to public health. Most emerging infectious disease agents in humans are of zoonotic origin. Bats are important reservoir hosts of many highly lethal zoonotic viruses and have been implicated in numerous emerging infectious disease events in recent years. It is essential to enhance our knowledge and understanding of the genetic diversity of the bat-associated viruses to prevent future outbreaks. To facilitate further research, we constructed the database of bat-associated viruses (DBatVir). Known viral sequences detected in bat samples were manually collected and curated, along with the related metadata, such as the sampling time, location, bat species and specimen type. Additional information concerning the bats, including common names, diet type, geographic distribution and phylogeny were integrated into the database to bridge the gap between virologists and zoologists. The database currently covers >4100 bat-associated animal viruses of 23 viral families detected from 196 bat species in 69 countries worldwide. It provides an overview and snapshot of the current research regarding bat-associated viruses, which is essential now that the field is rapidly expanding. With a user-friendly interface and integrated online bioinformatics tools, DBatVir provides a convenient and powerful platform for virologists and zoologists to analyze the virome diversity of bats, as well as for epidemiologists and public health researchers to monitor and track current and future bat-related infectious diseases. Database URL: http://www.mgc.ac.cn/DBatVir/",2014 Mar 18,"['Chen, Lihong', 'Liu, Bo', 'Yang, Jian', 'Jin, Qi']",Database (Oxford),,,True
e80ffcae95f83bc7e4353e746ec75187eb61281e,PMC,Multistep-Ahead Air Passengers Traffic Prediction with Hybrid ARIMA-SVMs Models,http://dx.doi.org/10.1155/2014/567246,PMC3958729,24723814,CC BY,"The hybrid ARIMA-SVMs prediction models have been established recently, which take advantage of the unique strength of ARIMA and SVMs models in linear and nonlinear modeling, respectively. Built upon this hybrid ARIMA-SVMs models alike, this study goes further to extend them into the case of multistep-ahead prediction for air passengers traffic with the two most commonly used multistep-ahead prediction strategies, that is, iterated strategy and direct strategy. Additionally, the effectiveness of data preprocessing approaches, such as deseasonalization and detrending, is investigated and proofed along with the two strategies. Real data sets including four selected airlines' monthly series were collected to justify the effectiveness of the proposed approach. Empirical results demonstrate that the direct strategy performs better than iterative one in long term prediction case while iterative one performs better in the case of short term prediction. Furthermore, both deseasonalization and detrending can significantly improve the prediction accuracy for both strategies, indicating the necessity of data preprocessing. As such, this study contributes as a full reference to the planners from air transportation industries on how to tackle multistep-ahead prediction tasks in the implementation of either prediction strategy.",2014 Feb 27,"['Ming, Wei', 'Bao, Yukun', 'Hu, Zhongyi', 'Xiong, Tao']",ScientificWorldJournal,,,True
b3e94bce63878a41d45d22c012a9492d079b3b7f,PMC,NTCP and Beyond: Opening the Door to Unveil Hepatitis B Virus Entry,http://dx.doi.org/10.3390/ijms15022892,PMC3958888,24557582,CC BY,"Chronic hepatitis B virus (HBV) infection, affecting approximately 240 million people worldwide, is a major public health problem that elevates the risk of developing liver cirrhosis and hepatocellular carcinoma. Given that current anti-HBV drugs are limited to interferon-based regimens and nucleos(t)ide analogs, the development of new anti-HBV agents is urgently needed. The viral entry process is generally an attractive target implicated in antiviral strategies. Using primary cells from humans and Tupaia belangeri, as well as HepaRG cells, important determinants of viral entry have been achieved. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was identified as an HBV entry receptor and enabled the establishment of a susceptible cell line that can efficiently support HBV infection. This finding will allow a deeper understanding of the requirements for efficient HBV infection, including the elucidation of the molecular entry mechanism. In addition, pharmacological studies suggest that NTCP is able to serve as a therapeutic target. This article summarizes our current knowledge on the mechanisms of HBV entry and the role of NTCP in this process.",2014 Feb 19,"['Watashi, Koichi', 'Urban, Stephan', 'Li, Wenhui', 'Wakita, Takaji']",Int J Mol Sci,,,True
108ebac20ee26fd05a2ba7ad43523957c34d871e,PMC,How Change of Public Transportation Usage Reveals Fear of the SARS Virus in a City,http://dx.doi.org/10.1371/journal.pone.0089405,PMC3960095,24647278,CC BY,"The outbreaks of the severe acute respiratory syndrome (SARS) epidemic in 2003 resulted in unprecedented impacts on people's daily life. One of the most significant impacts to people is the fear of contacting the SARS virus while engaging daily routine activity. Here we use data from daily underground ridership in Taipei City and daily reported new SARS cases in Taiwan to model the dynamics of the public fear of the SARS virus during the wax and wane of the SARS period. We found that for each reported new SARS case there is an immediate loss of about 1200 underground ridership (the fresh fear). These daily loss rates dissipate to the following days with an e-folding time of about 28 days, reflecting the public perception on the risk of contacting SARS virus when traveling with the underground system (the residual fear). About 50% of daily ridership was lost during the peak of the 2003 SARS period, compared with the loss of 80% daily ridership during the closure of the underground system after Typhoon Nari, the loss of 50–70% ridership due to the closure of the governmental offices and schools during typhoon periods, and the loss of 60% daily ridership during Chinese New Year holidays.",2014 Mar 19,"Wang, Kuo-Ying",PLoS One,,,True
638c36249e56a71ae71edd5391b1ca7fafd82daf,PMC,Contrasting Patterns in Mammal–Bacteria Coevolution: Bartonella and Leptospira in Bats and Rodents,http://dx.doi.org/10.1371/journal.pntd.0002738,PMC3961187,24651646,CC BY,"BACKGROUND: Emerging bacterial zoonoses in bats and rodents remain relatively understudied. We conduct the first comparative host–pathogen coevolutionary analyses of bacterial pathogens in these hosts, using Bartonella spp. and Leptospira spp. as a model. METHODOLOGY/PRINCIPAL FINDINGS: We used published genetic data for 51 Bartonella genotypes from 24 bat species, 129 Bartonella from 38 rodents, and 26 Leptospira from 20 bats. We generated maximum likelihood and Bayesian phylogenies for hosts and bacteria, and tested for coevoutionary congruence using programs ParaFit, PACO, and Jane. Bartonella spp. and their bat hosts had a significant coevolutionary fit (ParaFitGlobal = 1.9703, P≤0.001; m(2) global value = 7.3320, P≤0.0001). Bartonella spp. and rodent hosts also indicated strong overall patterns of cospeciation (ParaFitGlobal = 102.4409, P≤0.001; m(2) global value = 86.532, P≤0.0001). In contrast, we were unable to reject independence of speciation events in Leptospira and bats (ParaFitGlobal = 0.0042, P = 0.84; m(2) global value = 4.6310, P = 0.5629). Separate analyses of New World and Old World data subsets yielded results congruent with analysis from entire datasets. We also conducted event-based cophylogeny analyses to reconstruct likely evolutionary histories for each group of pathogens and hosts. Leptospira and bats had the greatest number of host switches per parasite (0.731), while Bartonella and rodents had the fewest (0.264). CONCLUSIONS/SIGNIFICANCE: In both bat and rodent hosts, Bartonella exhibits significant coevolution with minimal host switching, while Leptospira in bats lacks evolutionary congruence with its host and has high number of host switches. Reasons underlying these variable coevolutionary patterns in host range are likely due to differences in disease-specific transmission and host ecology. Understanding the coevolutionary patterns and frequency of host-switching events between bacterial pathogens and their hosts will allow better prediction of spillover between mammal reservoirs, and ultimately to humans.",2014 Mar 20,"['Lei, Bonnie R.', 'Olival, Kevin J.']",PLoS Negl Trop Dis,,,True
dacb58b5ac7adedfeb44dde5632c503c5d37548f,PMC,De novo Fatty Acid Biosynthesis Contributes Significantly to Establishment of a Bioenergetically Favorable Environment for Vaccinia Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1004021,PMC3961357,24651651,CC BY,"The poxvirus life cycle, although physically autonomous from the host nucleus, is nevertheless dependent upon cellular functions. A requirement for de novo fatty acid biosynthesis was implied by our previous demonstration that cerulenin, a fatty acid synthase inhibitor, impaired vaccinia virus production. Here we show that additional inhibitors of this pathway, TOFA and C75, reduce viral yield significantly, with partial rescue provided by exogenous palmitate, the pathway's end-product. Palmitate's major role during infection is not for phospholipid synthesis or protein palmitoylation. Instead, the mitochondrial import and β-oxidation of palmitate are essential, as shown by the impact of etomoxir and trimetazidine, which target these two processes respectively. Moreover, the impact of these inhibitors is exacerbated in the absence of exogenous glucose, which is otherwise dispensable for infection. In contrast to glucose, glutamine is essential for productive viral infection, providing intermediates that sustain the TCA cycle (anaplerosis). Cumulatively, these data suggest that productive infection requires the mitochondrial β-oxidation of palmitate which drives the TCA cycle and energy production. Additionally, infection causes a significant rise in the cellular oxygen consumption rate (ATP synthesis) that is ablated by etomoxir. The biochemical progression of the vaccinia life cycle is not impaired in the presence of TOFA, C75, or etomoxir, although the levels of viral DNA and proteins synthesized are somewhat diminished. However, by reversibly arresting infections at the onset of morphogenesis, and then monitoring virus production after release of the block, we determined that virion assembly is highly sensitive to TOFA and C75. Electron microscopic analysis of cells released into C75 revealed fragmented aggregates of viroplasm which failed to be enclosed by developing virion membranes. Taken together, these data indicate that vaccinia infection, and in particular virion assembly, relies on the synthesis and mitochondrial import of fatty acids, where their β-oxidation drives robust ATP production.",2014 Mar 20,"['Greseth, Matthew D.', 'Traktman, Paula']",PLoS Pathog,,,True
740523d9e53ac786c0a45c790320c219cd0031a4,PMC,MAVS-MKK7-JNK2 Defines a Novel Apoptotic Signaling Pathway during Viral Infection,http://dx.doi.org/10.1371/journal.ppat.1004020,PMC3961361,24651600,CC BY,"Viral infection induces innate immunity and apoptosis. Apoptosis is an effective means to sacrifice virus-infected host cells and therefore restrict the spread of pathogens. However, the underlying mechanisms of this process are still poorly understood. Here, we show that the mitochondrial antiviral signaling protein (MAVS/VISA/Cardif/IPS-1) is critical for SeV (Sendai virus)-induced apoptosis. MAVS specifically activates c-Jun N-terminal kinase 2 (JNK2) but not other MAP kinases. Jnk2−/− cells, but not Jnk1−/− cells, are unable to initiate virus-induced apoptosis and SeV further fails to trigger apoptosis in MAPK kinase 7 (MKK7) knockout (Mkk7−/−) cells. Mechanistically, MAVS recruits MKK7 onto mitochondria via its 3D domain, which subsequently phosphorylates JNK2 and thus activates the apoptosis pathway. Consistently, Jnk2−/− mice, but not Jnk1−/− mice, display marked inflammatory injury in lung and liver after viral challenge. Collectively, we have identified a novel signaling pathway, involving MAVS-MKK7-JNK2, which mediates virus-induced apoptosis and highlights the indispensable role of mitochondrial outer membrane in host defenses.",2014 Mar 20,"['Huang, Yuefeng', 'Liu, Heng', 'Li, Senlin', 'Tang, Yijun', 'Wei, Bo', 'Yu, Huansha', 'Wang, Chen']",PLoS Pathog,,,True
9027b4d1324273bed34f667f3d61d2536e9fd316,PMC,"Concurrent Measurement of Dynamic Changes in Viral Load, Serum Enzymes, T Cell Subsets, and Cytokines in Patients with Severe Fever with Thrombocytopenia Syndrome",http://dx.doi.org/10.1371/journal.pone.0091679,PMC3962368,24658451,CC BY,"Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection caused by a novel Bunyavirus. Analysis on the dynamic changes of clinical, laboratory, and immunological abnormalities associated with SFTS in a concurrent study is lacking. Thirty-three SFTS patients were admitted to Jiangsu People's Hospital, Nanjing, China, and diagnosis was made based on the clinical symptoms and positive viral RNA detected by RT-PCR. Four patients deceased and twenty-nine survived. Blood samples were collected every other day between Day 5 and Day 15 from the onset of fever. Samples from healthy volunteers were used as normal controls. Peak viral RNA load, serum enzymes, IL-6, and IL-10 were significantly higher in deceased patients compared to survivors. Viral load, serum enzymes, and cytokines declined in survivors within 2 weeks from onset of fever. CD69+ T cells were elevated early after infection while HLA-DR+ and CTLA4+ T cells were elevated during the recovery phase of those who survived. High level SFTSV viral load was concurrently observed with reduced PLT, elevated serum enzymes, elevated pro-inflammatory and anti-inflammatory cytokines, and activation of CD69+ T cells. The degree and pattern of changes in these parameters may indicate the clinical outcome in SFTSV-infected patients.",2014 Mar 21,"['Li, Jun', 'Han, Yaping', 'Xing, Yiping', 'Li, Shuang', 'Kong, Lianhua', 'Zhang, Yongxiang', 'Zhang, Lili', 'Liu, Ning', 'Wang, Qian', 'Wang, Shixia', 'Lu, Shan', 'Huang, Zuhu']",PLoS One,,,True
3db3a962e710f4712e14a5162a9e7f3f136696f6,PMC,Multi-Organ Lesions in Suckling Mice Infected with SARS-Associated Mammalian Reovirus Linked with Apoptosis Induced by Viral Proteins μ1 and σ1,http://dx.doi.org/10.1371/journal.pone.0092678,PMC3963933,24664247,CC BY,"We reported the isolation and characterization of a novel mammalian reassortant reovirus BYD1 that may have played an accomplice role with SARS-coronavirus during the 2003 SARS pandemic. The pathogenic mechanism of this novel reovirus is unknown. Reovirus pathogenicity has been associated with virus-induced apoptosis in cultured cells and in vivo. The reovirus outer capsid protein μ1 is recognized as the primary determinant of reovirus-induced apoptosis. Here, we investigated the apoptosis induced by BYD1, its outer capsid protein μ1, and its cell-attachment protein σ1 to understand the pathogenesis of BYD1. We also investigated BYD1 caused systemic complications in suckling mice. Under electron microscopy, BYD1-infected cells showed characteristics typical of apoptosis. Notably, ectopically expressed μ1 and σ1 induced similar pathological apoptosis, independent of BYD1 infection, in host cells in which they were expressed, which suggests that μ1 and σ1 are both apoptotic virulence factors. Consistent with previous reports of reovirus pathogenicity, suckling mice intracranially inoculated with BYD1 developed central nerve damage, myocarditis, and pneumonia. Collectively, our data suggest that BYD1 μ1- and σ1-induced apoptosis is involved in the multi-organ lesions in a suckling mouse BYD1 infection model.",2014 Mar 24,"['Song, Lihua', 'Lu, Yongfeng', 'He, Jun', 'Yu, Yonghui', 'Zuo, Tingting', 'Li, Yanwei', 'Zhu, Hong', 'Duan, Qing']",PLoS One,,,True
a135f7028fe8bfd36c791323bf28623c06c7b7fb,PMC,AVPdb: a database of experimentally validated antiviral peptides targeting medically important viruses,http://dx.doi.org/10.1093/nar/gkt1191,PMC3964995,24285301,CC BY,"Antiviral peptides (AVPs) have exhibited huge potential in inhibiting viruses by targeting various stages of their life cycle. Therefore, we have developed AVPdb, available online at http://crdd.osdd.net/servers/avpdb, to provide a dedicated resource of experimentally verified AVPs targeting over 60 medically important viruses including Influenza, HCV, HSV, RSV, HBV, DENV, SARS, etc. However, we have separately provided HIV inhibiting peptides in ‘HIPdb’. AVPdb contains detailed information of 2683 peptides, including 624 modified peptides experimentally tested for antiviral activity. In modified peptides a chemical moiety is attached for increasing their efficacy and stability. Detailed information include: peptide sequence, length, source, virus targeted, virus family, cell line used, efficacy (qualitative/quantitative), target step/protein, assay used in determining the efficacy and PubMed reference. The database also furnishes physicochemical properties and predicted structure for each peptide. We have provided user-friendly browsing and search facility along with other analysis tools to help the users. Entering of many synthetic peptide-based drugs in various stages of clinical trials reiterate the importance for the AVP resources. AVPdb is anticipated to cater to the needs of scientific community working for the development of antiviral therapeutics.",2014 Jan 1,"['Qureshi, Abid', 'Thakur, Nishant', 'Tandon, Himani', 'Kumar, Manoj']",Nucleic Acids Res,,,True
2d2d787fd72d87b38275e4deb4b160ad8c80338c,PMC,Proteomics Analysis of the DF-1 Chicken Fibroblasts Infected with Avian Reovirus Strain S1133,http://dx.doi.org/10.1371/journal.pone.0092154,PMC3965424,24667214,CC BY,"BACKGROUND: Avian reovirus (ARV) is a member of the Orthoreovirus genus in the Reoviridae family. It is the etiological agent of several diseases, among which viral arthritis and malabsorption syndrome are the most commercially important, causing considerable economic losses in the poultry industry. Although a small but increasing number of reports have characterized some aspects of ARV infection, global changes in protein expression in ARV-infected host cells have not been examined. The current study used a proteomics approach to obtain a comprehensive view of changes in protein levels in host cells upon infection by ARV. METHODOLOGY AND PRINCIPAL FINDINGS: The proteomics profiles of DF-1 chicken fibroblast cells infected with ARV strain S1133 were analyzed by two-dimensional differential-image gel electrophoresis. The majority of protein expression changes (≥1.5 fold, p<0.05) occurred at 72 h post-infection. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry identified 51 proteins with differential expression levels, including 25 that were upregulated during ARV infection and 26 that were downregulated. These proteins were divided into eight groups according to biological function: signal transduction, stress response, RNA processing, the ubiquitin-proteasome pathway, lipid metabolism, carbohydrate metabolism, energy metabolism, and cytoskeleton organization. They were further examined by immunoblotting to validate the observed alterations in protein expression. CONCLUSION/SIGNIFICANCE: This is the first report of a time-course proteomic analysis of ARV-infected host cells. Notably, all identified proteins involved in signal transduction, RNA processing, and the ubiquitin-proteasome pathway were downregulated in infected cells, whereas proteins involved in DNA synthesis, apoptosis, and energy production pathways were upregulated. In addition, other differentially expressed proteins were linked with the cytoskeleton, metabolism, redox regulation, and stress response. These proteomics data provide valuable information about host cell responses to ARV infection and will facilitate further studies of the molecular mechanisms underlying ARV pathogenesis.",2014 Mar 25,"['Chen, Wen-Ting', 'Wu, Yi-Le', 'Chen, Ting', 'Cheng, Chao-Sheng', 'Chan, Hong-Lin', 'Chou, Hsiu-Chuan', 'Chen, Yi-Wen', 'Yin, Hsien-Sheng']",PLoS One,,,True
2ab24bbc71562ee67437db9fee7f83edb40f4de9,PMC,Imported Case of Acute Respiratory Tract Infection Associated with a Member of Species Nelson Bay Orthoreovirus,http://dx.doi.org/10.1371/journal.pone.0092777,PMC3965453,24667794,CC BY,"A Japanese man suffered from acute respiratory tract infection after returning to Japan from Bali, Indonesia in 2007. Miyazaki-Bali/2007, a strain of the species of Nelson Bay orthoreovirus, was isolated from the patient's throat swab using Vero cells, in which syncytium formation was observed. This is the sixth report describing a patient with respiratory tract infection caused by an orthoreovirus classified to the species of Nelson Bay orthoreovirus. Given the possibility that all of the patients were infected in Malaysia and Indonesia, prospective surveillance on orthoreovirus infections should be carried out in Southeast Asia. Furthermore, contact surveillance study suggests that the risk of human-to-human infection of the species of Nelson Bay orthoreovirus would seem to be low.",2014 Mar 25,"['Yamanaka, Atsushi', 'Iwakiri, Akira', 'Yoshikawa, Tomoki', 'Sakai, Kouji', 'Singh, Harpal', 'Himeji, Daisuke', 'Kikuchi, Ikuo', 'Ueda, Akira', 'Yamamoto, Seigo', 'Miura, Miho', 'Shioyama, Yoko', 'Kawano, Kimiko', 'Nagaishi, Tokiko', 'Saito, Minako', 'Minomo, Masumi', 'Iwamoto, Naoyasu', 'Hidaka, Yoshio', 'Sohma, Hirotoshi', 'Kobayashi, Takeshi', 'Kanai, Yuta', 'Kawagishi, Takehiro', 'Nagata, Noriyo', 'Fukushi, Shuetsu', 'Mizutani, Tetsuya', 'Tani, Hideki', 'Taniguchi, Satoshi', 'Fukuma, Aiko', 'Shimojima, Masayuki', 'Kurane, Ichiro', 'Kageyama, Tsutomu', 'Odagiri, Takato', 'Saijo, Masayuki', 'Morikawa, Shigeru']",PLoS One,,,True
e172d0ebcbb5e8488f19e2193ac9a9ed96f60efb,PMC,Commentary on the Regulation of Viral Proteins in Autophagy Process,http://dx.doi.org/10.1155/2014/962915,PMC3966343,24734254,CC BY,"The ability to subvert intracellular antiviral defenses is necessary for virus to survive as its replication occurs only in the host cells. Viruses have to modulate cellular processes and antiviral mechanisms to their own advantage during the entire virus life cycle. Autophagy plays important roles in cell regulation. Its function is not only to catabolize aggregate proteins and damaged organelles for recycling but also to serve as innate immunity to remove intracellular pathogenic elements such as viruses. Nevertheless, some viruses have evolved to negatively regulate autophagy by inhibiting its formation. Even more, some viruses have employed autophagy to benefit their replication. To date, there are more and more growing evidences uncovering the functions of many viral proteins to regulate autophagy through different cellular pathways. In this review, we will discuss the relationship between viruses and autophagy and summarize the current knowledge on the functions of viral proteins contributing to affect autophagy process.",2014 Mar 10,"['Cheng, Ching-Yuan', 'Chi, Pei-I', 'Liu, Hung-Jen']",Biomed Res Int,,,True
29ada2d0f89dbeee105c3f95b7df0ab204d9a444,PMC,"A New Species of Mesonivirus from the Northern Territory, Australia",http://dx.doi.org/10.1371/journal.pone.0091103,PMC3966781,24670468,CC BY,"Here we describe Casuarina virus (CASV), a new virus in the family Mesoniviridae. This is the first report of a mesonivirus in Australia, which extends the geographical range of this virus family to 3 continents. The virus was isolated in 2010 from Coquillettidia xanthogaster mosquitoes during surveillance in the suburbs of Darwin, the capital of the Northern Territory. Cryo-electron microscopy of the CASV virions revealed spherical particles of 65 nm in size with large club-shaped projections of approximately 15 nm in length. The new virus was most closely related to Alphamesonivirus 1, the only currently recognized species in the family. In 2013 a further 5 putative new mesonivirus species were described: Hana, Méno, Nsé, Moumo and Dak Nong viruses. The evolutionary distance between CASV and two of its closest relatives, Cavally and Hana viruses (Jones-Taylor-Thornton distance of 0.151 and 0.224, respectively), along with its isolation from a different genus of mosquitoes captured on a separate continent indicate that CASV is a new species.",2014 Mar 26,"['Warrilow, David', 'Watterson, Daniel', 'Hall, Roy A.', 'Davis, Steven S.', 'Weir, Richard', 'Kurucz, Nina', 'Whelan, Peter', 'Allcock, Richard', 'Hall-Mendelin, Sonja', 'O’Brien, Caitlin A.', 'Hobson-Peters, Jody']",PLoS One,,,True
9dbde5d85011e2cb16e7d996421db75323ea21c0,PMC,Molecular Characterization of Major Structural Protein Genes of Avian Coronavirus Infectious Bronchitis Virus Isolates in Southern China,http://dx.doi.org/10.3390/v5123007,PMC3967158,24304696,CC BY,"To gain comprehensive genetic information of circulating avian coronavirus infectious bronchitis virus (IBV) isolates in China, analysis of the phylogenetic tree, entropy of the amino acid sequences, and the positive selection as well as computational recombinations of S1, M and N genes of 23 IBV isolates was conducted in the present study. The phylogenetic trees based on the S1, M and N genes exhibited considerably different topology and the CK/CH/LSC/99I-type isolates were the predominant IBVs based on the phylogenetic analysis of S1 gene. Results of entropy of amino acid sequences revealed that the S1 gene had the largest variation; the M gene had less variation than the N gene. Positive selections were detected in not only S1 but also M and N gene proteins. In addition, five S1 gene recombinants between vaccine strain 4/91 and CK/CH/LSC/99I-type field isolate were confirmed. In conclusion, multiple IBV genotypes co-circulated; genetic diversity and positive selections existed in S1, M and N genes; 4/91 vaccine recombinants emerged in China. Our results show that field IBVs in China are continuing to evolve and vaccine strains may have an important role in the appearance of new IBV strains via recombination. In addition, the present study indicates that IBV evolution is driven by both generations of genetic diversity and selection.",2013 Dec 4,"['Mo, Mei-Lan', 'Li, Meng', 'Huang, Bai-Cheng', 'Fan, Wen-Sheng', 'Wei, Ping', 'Wei, Tian-Chao', 'Cheng, Qiu-Ying', 'Wei, Zheng-Ji', 'Lang, Ya-Hui']",Viruses,,,True
dcc4db04a2a7001e0b9931be5648c7f0cc233620,PMC,Make Yourself at Home: Viral Hijacking of the PI3K/Akt Signaling Pathway,http://dx.doi.org/10.3390/v5123192,PMC3967167,24351799,CC BY,"As viruses do not possess genes encoding for proteins required for translation, energy metabolism or membrane biosynthesis, they are classified as obligatory intracellular parasites that depend on a host cell to replicate. This genome limitation forces them to gain control over cellular processes to ensure their successful propagation. A diverse spectrum of virally encoded proteins tackling a broad spectrum of cellular pathways during most steps of the viral life cycle ranging from the host cell entry to viral protein translation has evolved. Since the host cell PI3K/Akt signaling pathway plays a critical regulatory role in many cellular processes including RNA processing, translation, autophagy and apoptosis, many viruses, in widely varying ways, target it. This review focuses on a number of remarkable examples of viral strategies, which exploit the PI3K/Akt signaling pathway for effective viral replication.",2013 Dec 16,"['Diehl, Nora', 'Schaal, Heiner']",Viruses,,,True
f1f24521928f5d8565a15a17bd7f79239a3d4116,PMC,A Schiff Base-Derived Copper (II) Complex Is a Potent Inducer of Apoptosis in Colon Cancer Cells by Activating the Intrinsic Pathway,http://dx.doi.org/10.1155/2014/540463,PMC3967396,24737979,CC BY,"Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents. In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential. In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)(2 ) Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC(50 )value of 2.87 μg/ml after 72 h of treatment. HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G(1 ) cell population. At a concentration of 6.25 μg/ml, the Cu(BrHAP)(2 ) compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells. Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken together, these results imply that the Cu(BrHAP)(2 ) compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents.",2014 Mar 5,"['Hajrezaie, Maryam', 'Paydar, Mohammadjavad', 'Zorofchian Moghadamtousi, Soheil', 'Hassandarvish, Pouya', 'Gwaram, Nura Suleiman', 'Zahedifard, Maryam', 'Rouhollahi, Elham', 'Karimian, Hamed', 'Looi, Chung Yeng', 'Ali, Hapipah Mohd', 'Abdul Majid, Nazia', 'Abdulla, Mahmood Ameen']",ScientificWorldJournal,,,True
c4aa9bb066a64db00b8bdd44d5c021c5603a09a2,PMC,"Comparison of Patients Hospitalized With Influenza A Subtypes H7N9, H5N1, and 2009 Pandemic H1N1",http://dx.doi.org/10.1093/cid/ciu053,PMC3967826,24488975,CC BY,"Background. Influenza A(H7N9) viruses isolated from humans show features suggesting partial adaptation to mammals. To provide insights into the pathogenesis of H7N9 virus infection, we compared risk factors, clinical presentation, and progression of patients hospitalized with H7N9, H5N1, and 2009 pandemic H1N1 (pH1N1) virus infections. Methods. We compared individual-level data from patients hospitalized with infection by H7N9 (n = 123), H5N1 (n = 119; 43 China, 76 Vietnam), and pH1N1 (n = 3486) viruses. We assessed risk factors for hospitalization after adjustment for age- and sex-specific prevalence of risk factors in the general Chinese population. Results. The median age of patients with H7N9 virus infection was older than other patient groups (63 years; P < .001) and a higher proportion was male (71%; P < .02). After adjustment for age and sex, chronic heart disease was associated with an increased risk of hospitalization with H7N9 (relative risk, 9.68; 95% confidence interval, 5.24–17.9). H7N9 patients had similar patterns of leukopenia, thrombocytopenia, and elevated alanine aminotransferase, creatinine kinase, C-reactive protein, and lactate dehydrogenase to those seen in H5N1 patients, which were all significantly different from pH1N1 patients (P < .005). H7N9 patients had a longer duration of hospitalization than either H5N1 or pH1N1 patients (P < .001), and the median time from onset to death was 18 days for H7N9 (P = .002) vs 11 days for H5N1 and 15 days for pH1N1 (P = .154). Conclusions. The identification of known risk factors for severe seasonal influenza and the more protracted clinical course compared with that of H5N1 suggests that host factors are an important contributor to H7N9 severity.",2014 Apr 15,"['Wang, Chen', 'Yu, Hongjie', 'Horby, Peter W.', 'Cao, Bin', 'Wu, Peng', 'Yang, Shigui', 'Gao, Hainv', 'Li, Hui', 'Tsang, Tim K.', 'Liao, Qiaohong', 'Gao, Zhancheng', 'Ip, Dennis K. M.', 'Jia, Hongyu', 'Jiang, Hui', 'Liu, Bo', 'Ni, Michael Y.', 'Dai, Xiahong', 'Liu, Fengfeng', 'Van Kinh, Nguyen', 'Liem, Nguyen Thanh', 'Hien, Tran Tinh', 'Li, Yu', 'Yang, Juan', 'Wu, Joseph T.', 'Zheng, Yaming', 'Leung, Gabriel M.', 'Farrar, Jeremy J.', 'Cowling, Benjamin J.', 'Uyeki, Timothy M.', 'Li, Lanjuan']",Clin Infect Dis,,,True
56ac442721c9e0f335024cb4e414c9f00bc53aea,PMC,Viral OTU Deubiquitinases: A Structural and Functional Comparison,http://dx.doi.org/10.1371/journal.ppat.1003894,PMC3968130,24676359,CC BY,"Recent studies have revealed that proteases encoded by three very diverse RNA virus groups share structural similarity with enzymes of the Ovarian Tumor (OTU) superfamily of deubiquitinases (DUBs). The publication of the latest of these reports in quick succession prevented proper recognition and discussion of the shared features of these viral enzymes. Here we provide a brief structural and functional comparison of these virus-encoded OTU DUBs. Interestingly, although their shared structural features and substrate specificity tentatively place them within the same protease superfamily, they also show interesting differences that trigger speculation as to their origins.",2014 Mar 27,"['Bailey-Elkin, Ben A.', 'van Kasteren, Puck B.', 'Snijder, Eric J.', 'Kikkert, Marjolein', 'Mark, Brian L.']",PLoS Pathog,,,True
2a5d09bdb532096261be55490d99eb996e05ea18,PMC,Influenza-Like Illnesses in Senegal: Not Only Focus on Influenza Viruses,http://dx.doi.org/10.1371/journal.pone.0093227,PMC3968133,24675982,CC BY,"Influenza surveillance in African countries was initially restricted to the identification of circulating strains. In Senegal, the network has recently been enhanced (i) to include epidemiological data from Dakar and other regions and (ii) to extend virological surveillance to other respiratory viruses. Epidemiological data from the sentinel sites is transmitted daily by mobile phone. The data include those for other febrile syndromes similar to influenza-like illnesses (ILI), corresponding to integrated approach. Also, clinical samples are randomly selected and analyzed for influenza and other respiratory viruses. There were 101,640 declared visits to the 11 sentinel sites between week 11-2012 and week 35-2013; 22% of the visits were for fever syndromes and 23% of the cases of fever syndrome were ILI. Influenza viruses were the second most frequent cause of ILI (20%), after adenoviruses (21%) and before rhinoviruses (18%) and enteroviruses (15%). Co-circulation and co-infection were frequent and were responsible for ILI peaks. The first months of implementation of the enhanced surveillance system confirmed that viruses other the influenza make large contributions to influenza-like illnesses. It is therefore important to consider these etiologies in the development of strategies to reduce respiratory infections. More informative tools and research studies are required to assess the burden of respiratory infections in developing countries.",2014 Mar 27,"['Dia, Ndongo', 'Diene Sarr, Fatoumata', 'Thiam, Diamilatou', 'Faye Sarr, Tening', 'Espié, Emmanuelle', 'OmarBa, Ibrahim', 'Coly, Malang', 'Niang, Mbayame', 'Richard, Vincent', None]",PLoS One,,,True
d5325b37145bcf18e4b7bf64b7c93ceef20273b5,PMC,Orsay virus utilizes ribosomal frameshifting to express a novel protein that is incorporated into virions(),http://dx.doi.org/10.1016/j.virol.2013.12.016,PMC3969245,24503084,CC BY,"Orsay virus is the first identified virus that is capable of naturally infecting Caenorhabditis elegans. Although it is most closely related to nodaviruses, Orsay virus differs from nodaviruses in its genome organization. In particular, the Orsay virus RNA2 segment encodes a putative novel protein of unknown function, termed delta, which is absent from all known nodaviruses. Here we present evidence that Orsay virus utilizes a ribosomal frameshifting strategy to express a novel fusion protein from the viral capsid (alpha) and delta ORFs. Moreover, the fusion protein was detected in purified virus fractions, demonstrating that it is most likely incorporated into Orsay virions. Furthermore, N-terminal sequencing of both the fusion protein and the capsid protein demonstrated that these proteins must be translated from a non-canonical initiation site. While the function of the alpha–delta fusion remains cryptic, these studies provide novel insights into the fundamental properties of this new clade of viruses.",2014 Feb,"['Jiang, Hongbing', 'Franz, Carl J.', 'Wu, Guang', 'Renshaw, Hilary', 'Zhao, Guoyan', 'Firth, Andrew E.', 'Wang, David']",Virology,,,False
d3d998de1e3cb950c425decbadc73af2c26102fb,PMC,More Novel Hantaviruses and Diversifying Reservoir Hosts — Time for Development of Reservoir-Derived Cell Culture Models?,http://dx.doi.org/10.3390/v6030951,PMC3970132,24576845,CC BY,"Due to novel, improved and high-throughput detection methods, there is a plethora of newly identified viruses within the genus Hantavirus. Furthermore, reservoir host species are increasingly recognized besides representatives of the order Rodentia, now including members of the mammalian orders Soricomorpha/Eulipotyphla and Chiroptera. Despite the great interest created by emerging zoonotic viruses, there is still a gross lack of in vitro models, which reflect the exclusive host adaptation of most zoonotic viruses. The usually narrow host range and genetic diversity of hantaviruses make them an exciting candidate for studying virus-host interactions on a cellular level. To do so, well-characterized reservoir cell lines covering a wide range of bat, insectivore and rodent species are essential. Most currently available cell culture models display a heterologous virus-host relationship and are therefore only of limited value. Here, we review the recently established approaches to generate reservoir-derived cell culture models for the in vitro study of virus-host interactions. These successfully used model systems almost exclusively originate from bats and bat-borne viruses other than hantaviruses. Therefore we propose a parallel approach for research on rodent- and insectivore-borne hantaviruses, taking the generation of novel rodent and insectivore cell lines from wildlife species into account. These cell lines would be also valuable for studies on further rodent-borne viruses, such as orthopox- and arenaviruses.",2014 Feb 26,"['Eckerle, Isabella', 'Lenk, Matthias', 'Ulrich, Rainer G.']",Viruses,,,True
1d0c8b03f2da34c55161d6205a97d06d373762c0,PMC,Isolation and Identification of Feline Herpesvirus Type 1 from a South China Tiger in China,http://dx.doi.org/10.3390/v6031004,PMC3970135,24590411,CC BY,"In 2012, an FHV-1-like virus was isolated from a tiger that presented with clinical signs of sialorrhea, sneezing and purulent rhinorrhea. Isolation was performed with the FK81 cell line, and the virus was identified by PCR, transmission electron microscopy (TEM), and the phylogenetic analysis of the partial thymidine kinase (TK) and glycoprotein B (gB) genes. A total of 253 bp of the TK gene and 566 bp of the gB gene were amplified from the trachea of the tiger by PCR/RT-PCR method. Phylogenetic analysis showed that the isolate belonged to the same cluster with other FHV-1 strains obtained from GenBank. Herpes-like viruses with an envelope and diameters of approximately 200 nm were observed in the culture supernatants of FK81 cells inoculated with samples from the tiger. The FHV-1 infection was confirmed by an animal challenge experiment in a cat model. Our finding extends the host range of FHV-1 and has implications for FHV-1 infection and South China tiger conservation.",2014 Feb 28,"['Sun, Heting', 'Li, Yuanguo', 'Jiao, Weiyi', 'Liu, Cunfa', 'Liu, Xiujuan', 'Wang, Haijun', 'Hua, Fuyou', 'Dong, Jianxiu', 'Fan, Shengtao', 'Yu, Zhijun', 'Gao, Yuwei', 'Xia, Xianzhu']",Viruses,,,True
1c956bc94ce590a7ca6c2ace2c0766bbbbfaa0e3,PMC,Development of Lectin-Linked Immunomagnetic Separation for the Detection of Hepatitis A Virus,http://dx.doi.org/10.3390/v6031037,PMC3970137,24599279,CC BY,"The accuracy and sensitivity of PCR-based methods for detection of hepatitis A virus (HAV) are dependent on the methods used to separate and concentrate the HAV from the infected cells. The pH and ionic strength affect the binding affinity of the virus to cells. In this study, we initially investigated the effects of pH (4.0–10.0) and metal ions (Fe(2+), Co(2+), Cu(2+), Mg(2+), K(+), and Ca(2+)) on the binding of HAV to oyster digestive cells. The lowest relative binding (RB) of HAV to the cells was found at pH 4.0 and in FeSO(4) solution (64.6% and 68.1%, respectively). To develop an alternative to antibody-dependent immunomagnetic separation prior to detection of HAV using RT-PCR, the binding of HAV to five lectins, peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA), Helix pomatia agglutinin (HPA), Ulex europaeus agglutinin (UEA-1) and soybean agglutinin (SBA), was evaluated using ELISAs. SBA showed significantly higher RB to HAV than the other lectins tested. In addition, HAV could be concentrated within 30 min using SBA-linked magnetic bead separation (SMS) prior to the RT-PCR assay. Our findings demonstrate the feasibility of using SMS combined with RT-PCR to detect HAV at dilutions ranging from 10(−1)–10(−4) of a HAV stock (titer: 10(4) TCID(50)/mL).",2014 Mar 4,"['Ko, Sang-Mu', 'Kwon, Joseph', 'Vaidya, Bipin', 'Choi, Jong Soon', 'Lee, Hee-Min', 'Oh, Myung-Joo', 'Bae, Hyeun-Jong', 'Cho, Se-Young', 'Oh, Kyung-Seo', 'Kim, Duwoon']",Viruses,,,True
507796937879c600ac886d0aa7080e73bedb5044,PMC,Molecular Characterizations of Subcellular Localization Signals in the Nucleocapsid Protein of Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.3390/v6031253,PMC3970149,24632575,CC BY,"The nucleolus is a dynamic subnuclear structure, which is crucial to the normal operation of the eukaryotic cell. The porcine epidemic diarrhea virus (PEDV), coronavirus nucleocapsid (N) protein, plays important roles in the process of virus replication and cellular infection. Virus infection and transfection showed that N protein was predominately localized in the cytoplasm, but also found in the nucleolus in Vero E6 cells. Furthermore, by utilizing fusion proteins with green fluorescent protein (GFP), deletion mutations or site-directed mutagenesis of PEDV N protein, coupled with live cell imaging and confocal microscopy, it was revealed that, a region spanning amino acids (aa), 71–90 in region 1 of the N protein was sufficient for nucleolar localization and R87 and R89 were critical for its function. We also identified two nuclear export signals (NES, aa221–236, and 325–364), however, only the nuclear export signal (aa325–364) was found to be functional in the context of the full-length N protein. Finally, the activity of this nuclear export signal (NES) was inhibited by the antibiotic Lepomycin B, suggesting that N is exported by a chromosome region maintenance 1-related export pathway.",2014 Mar 13,"['Shi, Da', 'Lv, Maojie', 'Chen, Jianfei', 'Shi, Hongyan', 'Zhang, Sha', 'Zhang, Xin', 'Feng, Li']",Viruses,,,True
4ff3cd099988eec4079249528fb8db645b3c9490,PMC,Hantavirus Immunology of Rodent Reservoirs: Current Status and Future Directions,http://dx.doi.org/10.3390/v6031317,PMC3970152,24638205,CC BY,"Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships.",2014 Mar 14,"['Schountz, Tony', 'Prescott, Joseph']",Viruses,,,True
d311746113fa03b25d129db6c7acc6182499d679,PMC,Asthmatics with exacerbation during acute respiratory illness exhibit unique transcriptional signatures within the nasal mucosa,http://dx.doi.org/10.1186/gm520,PMC3971347,24433494,CC BY,"BACKGROUND: Acute respiratory illness is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular events characterizing acute respiratory illness-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of acute respiratory illness amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease. METHODS: Transcriptional profiling experiments were performed using the Agilent Whole Human Genome 4X44K array platform. Time point-based microarray and principal component analyses were conducted to identify and distinguish acute respiratory illness-associated transcriptional profiles over the course of our study. Gene enrichment analysis was conducted to identify biological processes over-represented within each acute respiratory illness-associated profile, and gene expression was subsequently confirmed by quantitative polymerase chain reaction. RESULTS: We found that acute respiratory illness is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during acute respiratory illness. Most strikingly, we report that people with asthma who experience acute respiratory illness-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair, and the expression of a newly described exacerbation-specific transcriptional signature. CONCLUSION: Findings from our study represent a significant contribution towards clarifying the complex molecular interactions that typify acute respiratory illness-induced asthma exacerbations.",2014 Jan 17,"['McErlean, Peter', 'Berdnikovs, Sergejs', 'Favoreto, Silvio', 'Shen, Junqing', 'Biyasheva, Assel', 'Barbeau, Rebecca', 'Eisley, Chris', 'Barczak, Andrea', 'Ward, Theresa', 'Schleimer, Robert P', 'Erle, David J', 'Boushey, Homer A', 'Avila, Pedro C']",Genome Med,,,True
2b9a00927657405449eeb367dc660fb109fe017c,PMC,Asthmatics with exacerbation during acute respiratory illness exhibit unique transcriptional signatures within the nasal mucosa,http://dx.doi.org/10.1186/gm520,PMC3971347,24433494,CC BY,"BACKGROUND: Acute respiratory illness is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular events characterizing acute respiratory illness-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of acute respiratory illness amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease. METHODS: Transcriptional profiling experiments were performed using the Agilent Whole Human Genome 4X44K array platform. Time point-based microarray and principal component analyses were conducted to identify and distinguish acute respiratory illness-associated transcriptional profiles over the course of our study. Gene enrichment analysis was conducted to identify biological processes over-represented within each acute respiratory illness-associated profile, and gene expression was subsequently confirmed by quantitative polymerase chain reaction. RESULTS: We found that acute respiratory illness is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during acute respiratory illness. Most strikingly, we report that people with asthma who experience acute respiratory illness-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair, and the expression of a newly described exacerbation-specific transcriptional signature. CONCLUSION: Findings from our study represent a significant contribution towards clarifying the complex molecular interactions that typify acute respiratory illness-induced asthma exacerbations.",2014 Jan 17,"['McErlean, Peter', 'Berdnikovs, Sergejs', 'Favoreto, Silvio', 'Shen, Junqing', 'Biyasheva, Assel', 'Barbeau, Rebecca', 'Eisley, Chris', 'Barczak, Andrea', 'Ward, Theresa', 'Schleimer, Robert P', 'Erle, David J', 'Boushey, Homer A', 'Avila, Pedro C']",Genome Med,,,False
8af0901c4f1252ca252a8618a346c88b3b65ae1b,PMC,Potential Geographic Distribution of the Novel Avian-Origin Influenza A (H7N9) Virus,http://dx.doi.org/10.1371/journal.pone.0093390,PMC3972139,24690878,CC BY,"BACKGROUND: In late March 2013, a new avian-origin influenza virus emerged in eastern China. This H7N9 subtype virus has since infected 240 people and killed 60, and has awakened global concern as a potential pandemic threat. Ecological niche modeling has seen increasing applications as a useful tool in mapping geographic potential and risk of disease transmission. METHODOLOGY/PRINCIPALS: We developed two datasets based on seasonal variation in Normalized Difference Vegetation Index (NDVI) from the MODIS sensor to characterize environmental dimensions of H7N9 virus. One-third of well-documented cases was used to test robustness of models calibrated based on the remaining two-thirds, and model significance was tested using partial ROC approaches. A final niche model was calibrated using all records available. CONCLUSIONS/SIGNIFICANCE: Central-eastern China appears to represent an area of high risk for H7N9 spread, but suitable areas were distributed more spottily in the north and only along the coast in the south; highly suitable areas also were identified in western Taiwan. Areas identified as presenting high risk for H7N9 spread tend to present consistent NDVI values through the year, whereas unsuitable areas show greater seasonal variation.",2014 Apr 1,"['Zhu, Gengping', 'Peterson, A. Townsend']",PLoS One,,,True
535c73393b8f68ef2f9081e1e07d0d0aa0d44a8c,PMC,New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) IV: Circulating ACE2 as a Biomarker of Systolic Dysfunction in Human Hypertension and Heart Failure,http://dx.doi.org/10.1371/journal.pone.0087845,PMC3972189,24691269,CC BY,"BACKGROUND: Growing evidence exists for soluble Angiotensin Converting Enzyme-2 (sACE2) as a biomarker in definitive heart failure (HF), but there is little information about changes in sACE2 activity in hypertension with imminent heart failure and in reverse remodeling. METHODS, FINDINGS: Patients with systolic HF (NYHAII-IV, enrolled for cardiac resynchronisation therapy, CRT, n = 100) were compared to hypertensive patients (n = 239) and to a healthy cohort (n = 45) with preserved ejection fraction (EF>50%) in a single center prospective clinical study. The status of the heart failure patients were checked before and after CRT. Biochemical (ACE and sACE2 activity, ACE concentration) and echocardiographic parameters (EF, left ventricular end-diastolic (EDD) and end-systolic diameter (ESD) and dP/dt) were measured. sACE2 activity negatively correlated with EF and positively with ESD and EDD in all patient's populations, while it was independent in the healthy cohort. sACE2 activity was already increased in the hypertensive group, where signs for imminent heart failure (slightly decreased EF and barely increased NT-proBNP levels) were detected. sACE2 activities further increased in patients with definitive heart failure (EF<50%), while sACE2 activities decreased with the improvement of the heart failure after CRT (reverse remodeling). Serum angiotensin converting enzyme (ACE) concentrations were lower in the diseased populations, but did not show a strong correlation with the echocardiographic parameters. CONCLUSIONS: Soluble ACE2 activity appears to be biomarker in heart failure, and in hypertension, where heart failure may be imminent. Our data suggest that sACE2 is involved in the pathomechanism of hypertension and HF.",2014 Apr 1,"['Úri, Katalin', 'Fagyas, Miklós', 'Mányiné Siket, Ivetta', 'Kertész, Attila', 'Csanádi, Zoltán', 'Sándorfi, Gábor', 'Clemens, Marcell', 'Fedor, Roland', 'Papp, Zoltán', 'Édes, István', 'Tóth, Attila', 'Lizanecz, Erzsébet']",PLoS One,,,True
1516a62bffb7478ad5cbec0bde15290baf5384a3,PMC,Apoptotic Response through a High Mobility Box 1 Protein-Dependent Mechanism in LPS/GalN-Induced Mouse Liver Failure and Glycyrrhizin-Mediated Inhibition,http://dx.doi.org/10.1371/journal.pone.0092884,PMC3972228,24690901,CC BY,"HMGB1 is a nuclear component involved in nucleosome stabilization and transcription regulation, but extracellularly it is able to serve as a potential late mediator of lethality. In the present study, we explored inflammation-promoting activity of HMGB1 and blockade of extracellular release of HMGB1 by glycyrrhizin (GL) in LPS/GalN-triggered mouse liver injury. At 1 to 10 h after LPS/GalN-treatment, mice were anesthetized to collect blood from heart puncture, and serum transaminase and HMGB1 were evaluated. Administration of LPS/GalN precipitated tissue injury associated with time-dependent alteration in HMGB1 serum levels. At 8 h nuclear immunoreactive products were remarkably reduced and extracellular HMGB1 expression was found exclusively in the pericentral foci. The treatment with GL significantly down-regulated the serum levels of ALT, AST, and HMGB1 in addition to the strong inhibition of tissue injury and extracellular immunoreactivity to HMGB1 and to acetylated-lysine. Furthermore, GL brought about a significant decrease in the number of apoptotic hepatocytes labeled with TUNEL-method. On the basis of these results, three apoptosis-associated genes were identified with microarray analysis and real-time PCR. The ChIP-assay revealed the binding of HMGB1 protein to Gsto1 promoter sequence in LPS/GalN-treated mice and the remarkable decrease in combined HMGB1 protein by GL. The current findings claim that a single injection of LPS/GalN might stimulate apoptosis of hepatocytes through the binding of HMGB1 protein to Gsto1 promoter region and that GL-treatment might prevent the apoptosis and inflammatory infiltrates caused with LPS/GalN-injection by disturbing the binding of HMGB1 protein to Gsto1 promoter sequence.",2014 Apr 1,"['Kuroda, Noriyuki', 'Inoue, Kouji', 'Ikeda, Tadayuki', 'Hara, Yaiko', 'Wake, Kenjiro', 'Sato, Tetsuji']",PLoS One,,,True
5dc0c03f8620c881a56b6b17db77b6ffe430ca28,PMC,Divergent Roles of Autophagy in Virus Infection,http://dx.doi.org/10.3390/cells2010083,PMC3972664,24709646,CC BY,"Viruses have played an important role in human evolution and have evolved diverse strategies to co-exist with their hosts. As obligate intracellular pathogens, viruses exploit and manipulate different host cell processes, including cellular trafficking, metabolism and immunity-related functions, for their own survival. In this article, we review evidence for how autophagy, a highly conserved cellular degradative pathway, serves either as an antiviral defense mechanism or, alternatively, as a pro-viral process during virus infection. Furthermore, we highlight recent reports concerning the role of selective autophagy in virus infection and how viruses manipulate autophagy to evade lysosomal capture and degradation.",2013 Jan 25,"['Chiramel, Abhilash I.', 'Brady, Nathan R.', 'Bartenschlager, Ralf']",Cells,,,True
de95f39159534068d4a1aef3e5d6a884d1c39656,PMC,"CD8+ T Lymphocyte Epitopes From The Herpes Simplex Virus Type 2 ICP27, VP22 and VP13/14 Proteins To Facilitate Vaccine Design And Characterization",http://dx.doi.org/10.3390/cells2010019,PMC3972665,24709642,CC BY,"CD8+ T cells have the potential to control HSV-2 infection. However, limited information has been available on CD8+ T cell epitopes or the functionality of antigen specific T cells during infection or following immunization with experimental vaccines. Peptide panels from HSV-2 proteins ICP27, VP22 and VP13/14 were selected from in silico predictions of binding to human HLA-A*0201 and mouse H-2Kd, Ld and Dd molecules. Nine previously uncharacterized CD8+ T cell epitopes were identified from HSV-2 infected BALB/c mice. HSV-2 specific peptide sequences stabilized HLA-A*02 surface expression with intermediate or high affinity binding. Peptide specific CD8+ human T cell lines from peripheral blood lymphocytes were generated from a HLA-A*02+ donor. High frequencies of peptide specific CD8+ T cell responses were elicited in mice by DNA vaccination with ICP27, VP22 and VP13/14, as demonstrated by CD107a mobilization. Vaccine driven T cell responses displayed a more focused immune response than those induced by viral infection. Furthermore, vaccination with ICP27 reduced viral shedding and reduced the clinical impact of disease. In conclusion, this study describes novel HSV-2 epitopes eliciting strong CD8+ T cell responses that may facilitate epitope based vaccine design and aid immunomonitoring of antigen specific T cell frequencies in preclinical and clinical settings.",2013 Jan 4,"['Platt, Rebecca J.', 'Khodai, Tansi', 'Townend, Tim J.', 'Bright, Helen H.', 'Cockle, Paul', 'Perez-Tosar, Luis', 'Webster, Rob', 'Champion, Brian', 'Hickling, Timothy P.', 'Mirza, Fareed']",Cells,,,True
8b248d30d63f97ce5c6aa8f1a6c61a8d7f4c914e,PMC,"Prevalence and correlates of influenza-a in piggery workers and pigs in two communities in Lagos, Nigeria",http://dx.doi.org/10.11604/pamj.2013.16.102.1450,PMC3972905,24711881,CC BY,"INTRODUCTION: Worldwide, three Influenza-A virus subtypes (H1N1, H1N2 and H3N2) in swine are major public health issues. In Nigeria, the existence of these subtypes in pigs has not been well studied. This study aimed at determining the prevalence and correlates of Influenza-A viruses circulating in piggery workers and pigs in Oke-aro and Goshen communities in Lagos, Nigeria. METHODS: Nasal swabs were taken from 197 consenting piggery workers and 281 randomly selected pigs to determine the prevalence of Influenza-A (H1, H3, H5) using Reverse Transcriptase Polymerase Chain Reaction test (gene M). An interviewer administered questionnaire was used to collect information on demography, Influenza-A related symptoms experienced, personal hygiene and management practices from the piggery workers. Descriptive statistics was used and chi square test performed at 5% significant level. RESULTS: All piggery workers and pigs’ nasal swabs tested negative for Influenza-A viruses, hence, association could not be tested. Mean age of piggery workers was 41 ± 13.6 years and 60% were females. Forty two percent were farm attendants, 38.0% were pig farmers and the rest butchers. Nineteen percent had history of headache; 14.0% had catarrh and cough; 4.0% had sore-throat; 5.0% had diarrhea; while 48.0% had muscle pain at the time of data collection. The mean body temperature for the pig workers was 36.5 ± 0.5 °C. A significant difference (p<0.05) existed among piggery workers who had muscle pains. CONCLUSION: Piggery workers and pigs in study area were free of Influenza-A (H1, H3, H5) viruses. The current practices of the piggery workers should be encouraged.",2013 Nov 17,"['Awosanya, Emmanuel Jolaoluwa', 'Ogundipe, Gabriel', 'Babalobi, Olutayo', 'Omilabu, Sunday']",Pan Afr Med J,,,True
45b4b6a49cc3373b0f67b014910073336dbca667,PMC,RNase L restricts the mobility of engineered retrotransposons in cultured human cells,http://dx.doi.org/10.1093/nar/gkt1308,PMC3973342,24371271,CC BY,"Retrotransposons are mobile genetic elements, and their mobility can lead to genomic instability. Retrotransposon insertions are associated with a diverse range of sporadic diseases, including cancer. Thus, it is not a surprise that multiple host defense mechanisms suppress retrotransposition. The 2′,5′-oligoadenylate (2-5A) synthetase (OAS)-RNase L system is a mechanism for restricting viral infections during the interferon antiviral response. Here, we investigated a potential role for the OAS-RNase L system in the restriction of retrotransposons. Expression of wild type (WT) and a constitutively active form of RNase L (NΔ385), but not a catalytically inactive RNase L mutant (R667A), impaired the mobility of engineered human LINE-1 (L1) and mouse intracisternal A-type particle retrotransposons in cultured human cells. Furthermore, WT RNase L, but not an inactive RNase L mutant (R667A), reduced L1 RNA levels and subsequent expression of the L1-encoded proteins (ORF1p and ORF2p). Consistently, confocal immunofluorescent microscopy demonstrated that WT RNase L, but not RNase L R667A, prevented formation of L1 cytoplasmic foci. Finally, siRNA-mediated depletion of endogenous RNase L in a human ovarian cancer cell line (Hey1b) increased the levels of L1 retrotransposition by ∼2-fold. Together, these data suggest that RNase L might function as a suppressor of structurally distinct retrotransposons.",2014 Apr 25,"['Zhang, Ao', 'Dong, Beihua', 'Doucet, Aurélien J.', 'Moldovan, John B.', 'Moran, John V.', 'Silverman, Robert H.']",Nucleic Acids Res,,,True
88599257eafdc8f7994d42af5dca697fd9283dd4,PMC,RNase L restricts the mobility of engineered retrotransposons in cultured human cells,http://dx.doi.org/10.1093/nar/gkt1308,PMC3973342,24371271,CC BY,"Retrotransposons are mobile genetic elements, and their mobility can lead to genomic instability. Retrotransposon insertions are associated with a diverse range of sporadic diseases, including cancer. Thus, it is not a surprise that multiple host defense mechanisms suppress retrotransposition. The 2′,5′-oligoadenylate (2-5A) synthetase (OAS)-RNase L system is a mechanism for restricting viral infections during the interferon antiviral response. Here, we investigated a potential role for the OAS-RNase L system in the restriction of retrotransposons. Expression of wild type (WT) and a constitutively active form of RNase L (NΔ385), but not a catalytically inactive RNase L mutant (R667A), impaired the mobility of engineered human LINE-1 (L1) and mouse intracisternal A-type particle retrotransposons in cultured human cells. Furthermore, WT RNase L, but not an inactive RNase L mutant (R667A), reduced L1 RNA levels and subsequent expression of the L1-encoded proteins (ORF1p and ORF2p). Consistently, confocal immunofluorescent microscopy demonstrated that WT RNase L, but not RNase L R667A, prevented formation of L1 cytoplasmic foci. Finally, siRNA-mediated depletion of endogenous RNase L in a human ovarian cancer cell line (Hey1b) increased the levels of L1 retrotransposition by ∼2-fold. Together, these data suggest that RNase L might function as a suppressor of structurally distinct retrotransposons.",2014 Apr 25,"['Zhang, Ao', 'Dong, Beihua', 'Doucet, Aurélien J.', 'Moldovan, John B.', 'Moran, John V.', 'Silverman, Robert H.']",Nucleic Acids Res,,,False
ab98d1b125aa0704e63adef426b27abd32e935f0,PMC,"Full Genome Virus Detection in Fecal Samples Using Sensitive Nucleic Acid Preparation, Deep Sequencing, and a Novel Iterative Sequence Classification Algorithm",http://dx.doi.org/10.1371/journal.pone.0093269,PMC3973683,24695106,CC BY,"We have developed a full genome virus detection process that combines sensitive nucleic acid preparation optimised for virus identification in fecal material with Illumina MiSeq sequencing and a novel post-sequencing virus identification algorithm. Enriched viral nucleic acid was converted to double-stranded DNA and subjected to Illumina MiSeq sequencing. The resulting short reads were processed with a novel iterative Python algorithm SLIM for the identification of sequences with homology to known viruses. De novo assembly was then used to generate full viral genomes. The sensitivity of this process was demonstrated with a set of fecal samples from HIV-1 infected patients. A quantitative assessment of the mammalian, plant, and bacterial virus content of this compartment was generated and the deep sequencing data were sufficient to assembly 12 complete viral genomes from 6 virus families. The method detected high levels of enteropathic viruses that are normally controlled in healthy adults, but may be involved in the pathogenesis of HIV-1 infection and will provide a powerful tool for virus detection and for analyzing changes in the fecal virome associated with HIV-1 progression and pathogenesis.",2014 Apr 2,"['Cotten, Matthew', 'Oude Munnink, Bas', 'Canuti, Marta', 'Deijs, Martin', 'Watson, Simon J.', 'Kellam, Paul', 'van der Hoek, Lia']",PLoS One,,,True
b8660d5f12c9a6a85b73207bc61291535c2700ce,PMC,Effect of cinnamon water extract on monocyte-to-macrophage differentiation and scavenger receptor activity,http://dx.doi.org/10.1186/1472-6882-14-90,PMC3973967,24602512,CC BY,"BACKGROUND: Water soluble cinnamon extract has been shown to increase insulin sensitivity and modulate macrophage activation, a desirable trait for the management of obesity or atherosclerosis. Our present study investigated whether cinnamon water extract (CWE) may influence the differentiation of monocytes into macrophages and the activity of macrophage scavenger receptors, commonly observed in atherosclerotic lesions. METHODS: We investigated the effect of CWE on the expression of various surface markers and the uptake of acetylated low density lipoprotein (LDL) in phorbol-12-myristate-13-acetate (PMA)-stimulated THP-1 cells. The protein levels of PMA or macrophage-colony stimulating factor (M-CSF)-stimulated type 1 macrophage scavenger receptor (SRA) were analyzed. Finally, the role of extracellar signal-related kinase (ERK) 1/2 in SRA synthesis and the effect of CWE on PMA-stimulated ERK1/2 were determined. RESULTS: CWE inhibited the differentiation of monocyte by decreasing the expression of CD11b, CD36 and SRA and the uptake of acetyl LDL. CWE suppressed the upregulation of SRA by M-CSF and modulated ERK1/2 activity, which was required for PMA-induced SRA synthesis. CONCLUSIONS: Our results demonstrate that CWE was able to interfere with monocyte differentiation and macrophage scavenger activity, indicating its potential in preventing the development of atherosclerotic lesions.",2014 Mar 7,"['Kang, Hee', 'Park, Sung-Hyun', 'Yun, Jeong-Moon', 'Nam, Tae-Gyu', 'Kim, Young-Eun', 'Kim, Dae-Ok', 'Kim, Youn Jung']",BMC Complement Altern Med,,,True
d2c72e2daceccd9b61cb182d778661e29256527b,PMC,Natural reservoirs for homologs of hepatitis C virus,http://dx.doi.org/10.1038/emi.2014.19,PMC3974340,26038514,CC BY,"Hepatitis C virus is considered a major public health problem, infecting 2%–3% of the human population. Hepatitis C virus infection causes acute and chronic liver disease, including chronic hepatitis, cirrhosis and hepatocellular carcinoma. In fact, hepatitis C virus infection is the most frequent indication for liver transplantation and a vaccine is not available. Hepatitis C virus displays a narrow host species tropism, naturally infecting only humans, although chimpanzees are also susceptible to experimental infection. To date, there is no evidence for an animal reservoir of viruses closely related to hepatitis C virus which may have crossed the species barrier to cause disease in humans and resulted in the current pandemic. In fact, due to this restricted host range, a robust immunocompetent small animal model is still lacking, hampering mechanistic analysis of virus pathogenesis, immune control and prophylactic vaccine development. Recently, several studies discovered new viruses related to hepatitis C virus, belonging to the hepaci- and pegivirus genera, in small wild mammals (rodents and bats) and domesticated animals which live in close contact with humans (dogs and horses). Genetic and biological characterization of these newly discovered hepatitis C virus-like viruses infecting different mammals will contribute to our understanding of the origins of hepatitis C virus in humans and enhance our ability to study pathogenesis and immune responses using tractable animal models. In this review article, we start with an introduction on the genetic diversity of hepatitis C virus and then focus on the newly discovered viruses closely related to hepatitis C virus. Finally, we discuss possible theories about the origin of this important viral human pathogen.",2014 Mar 26,"['Pfaender, Stephanie', 'Brown, Richard JP', 'Pietschmann, Thomas', 'Steinmann, Eike']",Emerg Microbes Infect,,,True
cf750714decab335f8990db7d0ca100506fa99fa,PMC,Novel Coronavirus and Astrovirus in Delaware Bay Shorebirds,http://dx.doi.org/10.1371/journal.pone.0093395,PMC3974748,24699424,CC BY,"BACKGROUND: Wild birds are an important but to some extent under-studied reservoir for emerging pathogens. We used unbiased sequencing methods for virus discovery in shorebird samples from the Delaware Bay, USA; an important feeding ground for thousands of migratory birds. FINDINGS: Analysis of shorebird fecal samples indicated the presence of a novel astrovirus and coronavirus. A sanderling sample yielded sequences with distant homology to avian nephritis virus 1, an astrovirus associated with acute nephritis in poultry. A ruddy turnstone sample yielded sequences with homology to deltacoronaviruses. CONCLUSIONS: Our findings highlight shorebirds as a virus reservoir and the need to closely monitor wild bird populations for the emergence of novel virus variants.",2014 Apr 3,"['Honkavuori, Kirsi S.', 'Briese, Thomas', 'Krauss, Scott', 'Sanchez, Maria D.', 'Jain, Komal', 'Hutchison, Stephen K.', 'Webster, Robert G.', 'Lipkin, W. Ian']",PLoS One,,,True
db80870c75793687f024d74e11d6a6d49333b1b6,PMC,Deep Sequencing to Identify the Causes of Viral Encephalitis,http://dx.doi.org/10.1371/journal.pone.0093993,PMC3974838,24699691,CC BY,"Deep sequencing allows for a rapid, accurate characterization of microbial DNA and RNA sequences in many types of samples. Deep sequencing (also called next generation sequencing or NGS) is being developed to assist with the diagnosis of a wide variety of infectious diseases. In this study, seven frozen brain samples from deceased subjects with recent encephalitis were investigated. RNA from each sample was extracted, randomly reverse transcribed and sequenced. The sequence analysis was performed in a blinded fashion and confirmed with pathogen-specific PCR. This analysis successfully identified measles virus sequences in two brain samples and herpes simplex virus type-1 sequences in three brain samples. No pathogen was identified in the other two brain specimens. These results were concordant with pathogen-specific PCR and partially concordant with prior neuropathological examinations, demonstrating that deep sequencing can accurately identify viral infections in frozen brain tissue.",2014 Apr 3,"['Chan, Benjamin K.', 'Wilson, Theodore', 'Fischer, Kael F.', 'Kriesel, John D.']",PLoS One,,,True
dcef588534b114e24a8c93a3eeeba8c1d11dd8a3,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,True
43c5fd0ced20ca85ba8a50b829674b806efb390d,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
b2cadb48524929ff83ac9705cb1d0a747b5bb1e8,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
93f839ddebf73ec46b504aafff560f7b3b50f22e,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
da0263344c5e5a938ffa955c8c6a2b9a12f8db6e,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
dae759b41afa898455c421249fda604375d8c973,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
d6043608d84c9697099d1e554487278e735942d2,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
2a70ba4400d14058b87d05736cf93bac434a01be,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
17815ef0b4f84d574710ea853ddfedb3b885dc69,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
07c02024be63150bd34d668fa5381061c23f07db,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
ba4c7eec34d93bb53325e6d925cb79ad04423cd1,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
b9a7147127a2c50c1d64f8e0236738301c534be0,PMC,IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion,http://dx.doi.org/10.1371/journal.ppat.1004048,PMC3974867,24699674,CC BY,"Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3's ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.",2014 Apr 3,"['Desai, Tanay M.', 'Marin, Mariana', 'Chin, Christopher R.', 'Savidis, George', 'Brass, Abraham L.', 'Melikyan, Gregory B.']",PLoS Pathog,,,False
a8d8faf148d930bc5d0b5908b0069c770123109e,PMC,A Human Lung Xenograft Mouse Model of Nipah Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1004063,PMC3974875,24699832,CC BY,"Nipah virus (NiV) is a member of the genus Henipavirus (family Paramyxoviridae) that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%). NiV can cause Acute Lung Injury (ALI) in humans, and human-to-human transmission has been observed in recent outbreaks of NiV. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells. The molecular mechanisms of NiV-associated ALI in the human respiratory tract are unknown. Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV. Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive “air” spaces filled with mucus and lined by cuboidal to flat epithelium. Following infection, NiV grows to high titers (10(7) TCID(50)/gram lung tissue) as early as 3 days post infection (pi). NiV targets both the endothelium as well as respiratory epithelium in the human lung tissues, and results in syncytia formation. NiV infection in the human lung results in the production of several cytokines and chemokines including IL-6, IP-10, eotaxin, G-CSF and GM-CSF on days 5 and 7 pi. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI. This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.",2014 Apr 3,"['Valbuena, Gustavo', 'Halliday, Hailey', 'Borisevich, Viktoriya', 'Goez, Yenny', 'Rockx, Barry']",PLoS Pathog,,,True
ee55aea26f816403476a7cb71816b8ecb1110329,PMC,iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking,http://dx.doi.org/10.3390/ijms15034915,PMC3975431,24651462,CC BY,"Nuclear receptors (NRs) are closely associated with various major diseases such as cancer, diabetes, inflammatory disease, and osteoporosis. Therefore, NRs have become a frequent target for drug development. During the process of developing drugs against these diseases by targeting NRs, we are often facing a problem: Given a NR and chemical compound, can we identify whether they are really in interaction with each other in a cell? To address this problem, a predictor called “iNR-Drug” was developed. In the predictor, the drug compound concerned was formulated by a 256-D (dimensional) vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine) algorithm. Compared with the existing prediction methods in this area, iNR-Drug not only can yield a higher success rate, but is also featured by a user-friendly web-server established at http://www.jci-bioinfo.cn/iNR-Drug/, which is particularly useful for most experimental scientists to obtain their desired data in a timely manner. It is anticipated that the iNR-Drug server may become a useful high throughput tool for both basic research and drug development, and that the current approach may be easily extended to study the interactions of drug with other targets as well.",2014 Mar 19,"['Fan, Yue-Nong', 'Xiao, Xuan', 'Min, Jian-Liang', 'Chou, Kuo-Chen']",Int J Mol Sci,,,True
ceb581975a05b3e74dc49c8efe7abffb656f6c69,PMC,iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking,http://dx.doi.org/10.3390/ijms15034915,PMC3975431,24651462,CC BY,"Nuclear receptors (NRs) are closely associated with various major diseases such as cancer, diabetes, inflammatory disease, and osteoporosis. Therefore, NRs have become a frequent target for drug development. During the process of developing drugs against these diseases by targeting NRs, we are often facing a problem: Given a NR and chemical compound, can we identify whether they are really in interaction with each other in a cell? To address this problem, a predictor called “iNR-Drug” was developed. In the predictor, the drug compound concerned was formulated by a 256-D (dimensional) vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine) algorithm. Compared with the existing prediction methods in this area, iNR-Drug not only can yield a higher success rate, but is also featured by a user-friendly web-server established at http://www.jci-bioinfo.cn/iNR-Drug/, which is particularly useful for most experimental scientists to obtain their desired data in a timely manner. It is anticipated that the iNR-Drug server may become a useful high throughput tool for both basic research and drug development, and that the current approach may be easily extended to study the interactions of drug with other targets as well.",2014 Mar 19,"['Fan, Yue-Nong', 'Xiao, Xuan', 'Min, Jian-Liang', 'Chou, Kuo-Chen']",Int J Mol Sci,,,False
b3e1d993fd5eb9e538a5acb4f5933d4bb6209878,PMC,Estimating the incidence reporting rates of new influenza pandemics at an early stage using travel data from the source country,http://dx.doi.org/10.1017/S0950268813002550,PMC3975527,24107289,CC BY,"During the surveillance of influenza pandemics, underreported data are a public health challenge that complicates the understanding of pandemic threats and can undermine mitigation efforts. We propose a method to estimate incidence reporting rates at early stages of new influenza pandemics using 2009 pandemic H1N1 as an example. Routine surveillance data and statistics of travellers arriving from Mexico were used. Our method incorporates changes in reporting rates such as linearly increasing trends due to the enhanced surveillance. From our results, the reporting rate was estimated at 0·46% during early stages of the pandemic in Mexico. We estimated cumulative incidence in the Mexican population to be 0·7% compared to 0·003% reported by officials in Mexico at the end of April. This method could be useful in estimation of actual cases during new influenza pandemics for policy makers to better determine appropriate control measures.",2014 May 10,"['CHONG, K. C.', 'FONG, H. F.', 'ZEE, C. Y.']",Epidemiol Infect,,,True
595019b82939f4fc62cda92fe6eedd34f6933c35,PMC,Aspergillus spp. colonization in exhaled breath condensate of lung cancer patients from Puglia Region of Italy,http://dx.doi.org/10.1186/1471-2466-14-22,PMC3975946,24548615,CC BY,"BACKGROUND: Airways of lung cancer patients are often colonized by fungi. Some of these colonizing fungi, under particular conditions, produce cancerogenic mycotoxins. Given the recent interest in the infective origin of lung cancer, with this preliminary study we aim to give our small contribution to this field of research by analysing the fungal microbiome of the exhaled breath condensate of lung cancer patients from Puglia, a region of Italy. METHODS: We enrolled 43 lung cancer patients and 21 healthy subjects that underwent exhaled breath condensate and bronchial brushing collection. The fungal incidence and nature of sample collected were analysed by using a selected media for Aspergillus species. RESULTS: For the first time we were able to analyse the fungal microbioma of the exhaled breath condensate. 27.9% of lung cancer patients showed a presence of Aspergillus niger, or A. ochraceus or Penicillium ssp. while none of the healthy subjects did so. CONCLUSION: The results confirmed the high percentage of fungal colonization of the airways of lung cancer patients from Puglia, suggesting the need to conduct further analyses in this field in order to evaluate the exact pathogenetic role of these fungi in lung cancer as well as to propose efficient, empirical therapy.",2014 Feb 18,"['Carpagnano, Giovanna E', 'Lacedonia, Donato', 'Palladino, Grazia Pia', 'Logrieco, Giuseppe', 'Crisetti, Elisabetta', 'Susca, Antonia', 'Logrieco, Antonio', 'Foschino-Barbaro, Maria P']",BMC Pulm Med,,,True
b45e94d7cf1a4ac89b45053ce5a24f03984f8e24,PMC,Association of Radiologic Findings with Mortality in Patients with Avian Influenza H7N9 Pneumonia,http://dx.doi.org/10.1371/journal.pone.0093885,PMC3976364,24705783,CC BY,"BACKGROUND: The novel H7N9 virus causes severe illness, including pneumonia and acute respiratory distress syndrome, with high rates of mortality. We investigated the association of initial radiologic characteristics obtained at admission with clinical outcomes in patients with avian influenza H7N9 pneumonia. METHODS: Demographics, comorbidities, clinical findings, radiologic appearance and scores of the affected lung parenchyma were compared between survivor group (n = 15) and mortality group (n = 7). Two radiologic scores were calculated, one using chest radiography and one using CT. Follow-up CT scans at discharge were analyzed in 12 patients of the survival group. RESULTS: All the patients in mortality group developed acute respiratory distress syndrome and required mechanical ventilation, while in the survival group 33% (5/15) developed acute respiratory distress syndrome (P<0.05) and 27% (4/15) required mechanical ventilation (P<0.05). The mean radiographic and CT scores of the mortality group were 50% higher compared to the survival group (P<0.05). ROC analysis revealed an area under curve of 0.738 for the radiographic score with an optimal cutoff value of a score of 19 for prediction of mortality, with a sensitivity of 71% and a specificity of 67%, and an area under curve of 0.833 for the CT score with an optimal cutoff value of a CT score of 21 for prediction of mortality, with a sensitivity of 86% and a specificity of 73%. The mean CT score of the affected lung parenchyma at discharge was 30% lower than the initial CT examination (P<0.05). CONCLUSION: High initial radiologic score is associated with mortality in patients with avian influenza H7N9 pneumonia.",2014 Apr 4,"['Feng, Feng', 'Jiang, Yebin', 'Yuan, Min', 'Shen, Jie', 'Yin, Huabin', 'Geng, Daoying', 'Xu, Jianrong', 'Hua, Yanqing', 'Shi, Jingyun', 'Shi, Yuxin', 'Zhang, Zhiyong']",PLoS One,,,True
ce48c5f903bc1435190dd7ddf21612cb0a8b0815,PMC,"Establishing and Applying a Schistosomiasis Early Warning Index (SEWI) in the Lower Yangtze River Region of Jiangsu Province, China",http://dx.doi.org/10.1371/journal.pone.0094012,PMC3976384,24705352,CC BY,"BACKGROUND: China has made remarkable progress in schistosomiasis control over the past decades. Transmission control has replaced morbidity control as the country moves towards the goal of elimination and the current challenge is to find a sensitive measure capable of gauging transmission risk in low-prevalence areas. The study aims to develop a Schistosomiasis Early Warning Index (SEWI) and demonstrate its use in Jiangsu Province along the lower Yangtze River. METHODOLOGY/PRINCIPAL FINDINGS: The Delphi approach, a structured communication technique, was used to develop the SEWI. Two rounds of interviews with 30 public health experts specialized in schistosomiasis control were conducted using 40 indicators that reflected different aspects of schistosomiasis transmission and control. The necessity, feasibility, and sensitivity of each indicator were assessed and the weight value of each indicator determined based on these experts' judgment. The system included 3 first-order indicators, 7 second-order indicators, and 30 third-order indicators. The 3 first-order indicators were endemic status, control measures, social and environmental factors, with the weight values 0.366, 0.343 and 0.291, respectively. For the 7 second-order indicators, the highest weight value was for control measures for snails (0.175) and the lowest for transmission route (0.110). We estimated and mapped the SEWI for endemic areas at the county scale in Jiangsu Province finding that the majority of the endemic areas were characterized as medium transmission risk (SEWI risk values between 0.3 and 0.6), while areas where transmission interruption had been officially declared showed SEWI values <0.30. A few isolated areas (e.g. endemic islands in the Yangtze River) produced SEWI values >0.60. These estimates are largely in agreement with the endemicity levels based on recent epidemiological surveys. CONCLUSIONS/SIGNIFICANCE: The SEWI should be useful for estimation of schistosomiasis transmission surveillance, particularly with reference to the elimination of the disease in China.",2014 Apr 4,"['Yang, Kun', 'Xu, Jun-Fang', 'Zhang, Jian-Feng', 'Li, Wei', 'He, Jian', 'Liang, Song', 'Bergquist, Robert']",PLoS One,,,True
96c886c9234855e0fb6ef46ea3c5b7c1c7abc652,PMC,In Silico Analysis Reveals Sequential Interactions and Protein Conformational Changes during the Binding of Chemokine CXCL-8 to Its Receptor CXCR1,http://dx.doi.org/10.1371/journal.pone.0094178,PMC3976404,24705928,CC BY,"Chemokine CXCL-8 plays a central role in human immune response by binding to and activate its cognate receptor CXCR1, a member of the G-protein coupled receptor (GPCR) family. The full-length structure of CXCR1 is modeled by combining the structures of previous NMR experiments with those from homology modeling. Molecular docking is performed to search favorable binding sites of monomeric and dimeric CXCL-8 with CXCR1 and a mutated form of it. The receptor-ligand complex is embedded into a lipid bilayer and used in multi ns molecular dynamics (MD) simulations. A multi-steps binding mode is proposed: (i) the N-loop of CXCL-8 initially binds to the N-terminal domain of receptor CXCR1 driven predominantly by electrostatic interactions; (ii) hydrophobic interactions allow the N-terminal Glu-Leu-Arg (ELR) motif of CXCL-8 to move closer to the extracellular loops of CXCR1; (iii) electrostatic interactions finally dominate the interaction between the N-terminal ELR motif of CXCL-8 and the EC-loops of CXCR1. Mutation of CXCR1 abrogates this mode of binding. The detailed binding process may help to facilitate the discovery of agonists and antagonists for rational drug design.",2014 Apr 4,"['Liou, Je-Wen', 'Chang, Fang-Tzu', 'Chung, Yi', 'Chen, Wen-Yi', 'Fischer, Wolfgang B.', 'Hsu, Hao-Jen']",PLoS One,,,True
23696844593c72dd8c4d74607ff26049336fe9b0,PMC,Geographic Access to High Capability Severe Acute Respiratory Failure Centers in the United States,http://dx.doi.org/10.1371/journal.pone.0094057,PMC3976413,24705417,CC BY,"OBJECTIVE: Optimal care of adults with severe acute respiratory failure requires specific resources and expertise. We sought to measure geographic access to these centers in the United States. DESIGN: Cross-sectional analysis of geographic access to high capability severe acute respiratory failure centers in the United States. We defined high capability centers using two criteria: (1) provision of adult extracorporeal membrane oxygenation (ECMO), based on either 2008–2013 Extracorporeal Life Support Organization reporting or provision of ECMO to 2010 Medicare beneficiaries; or (2) high annual hospital mechanical ventilation volume, based 2010 Medicare claims. SETTING: Nonfederal acute care hospitals in the United States. MEASUREMENTS AND MAIN RESULTS: We defined geographic access as the percentage of the state, region and national population with either direct or hospital-transferred access within one or two hours by air or ground transport. Of 4,822 acute care hospitals, 148 hospitals met our ECMO criteria and 447 hospitals met our mechanical ventilation criteria. Geographic access varied substantially across states and regions in the United States, depending on center criteria. Without interhospital transfer, an estimated 58.5% of the national adult population had geographic access to hospitals performing ECMO and 79.0% had geographic access to hospitals performing a high annual volume of mechanical ventilation. With interhospital transfer and under ideal circumstances, an estimated 96.4% of the national adult population had geographic access to hospitals performing ECMO and 98.6% had geographic access to hospitals performing a high annual volume of mechanical ventilation. However, this degree of geographic access required substantial interhospital transfer of patients, including up to two hours by air. CONCLUSIONS: Geographic access to high capability severe acute respiratory failure centers varies widely across states and regions in the United States. Adequate referral center access in the case of disasters and pandemics will depend highly on local and regional care coordination across political boundaries.",2014 Apr 4,"['Wallace, David J.', 'Angus, Derek C.', 'Seymour, Christopher W.', 'Yealy, Donald M.', 'Carr, Brendan G.', 'Kurland, Kristen', 'Boujoukos, Arthur', 'Kahn, Jeremy M.']",PLoS One,,,True
2b8c0be4a3bed5dbeea46401dcebe6c1263ead10,PMC,Decline in temperature and humidity increases the occurrence of influenza in cold climate,http://dx.doi.org/10.1186/1476-069X-13-22,PMC3978084,24678699,CC BY,"BACKGROUND: Both temperature and humidity may independently or jointly contribute to the risk of influenza infections. We examined the relations between the level and decrease of temperature, humidity and the risk of influenza A and B virus infections in a subarctic climate. METHODS: We conducted a case-crossover study among military conscripts (n = 892) seeking medical attention due to respiratory symptoms during their military training period and identified 66 influenza A and B cases by PCR or serology. Meteorological data such as measures of average and decline in ambient temperature and absolute humidity (AH) during the three preceding days of the onset (hazard period) and two reference periods, prior and after the onset were obtained. RESULTS: The average temperature preceding the influenza onset was −6.8 ± 5.6°C and AH 3.1 ± 1.3 g/m(3). A decrease in both temperature and AH during the hazard period increased the occurrence of influenza so that a 1°C decrease in temperature and 0.5 g decrease per m(3) in AH increased the estimated risk by 11% [OR 1.11 (1.03 to 1.20)] and 58% [OR 1.58 (1.28 to 1.96)], respectively. The occurrence of influenza infections was positively associated with both the average temperature [OR 1.10 per 1°C (95% confidence interval 1.02 to 1.19)] and AH [OR 1.25 per g/m(3) (1.05 to 1.49)] during the hazard period prior to onset. CONCLUSION: Our results demonstrate that a decrease rather than low temperature and humidity per se during the preceding three days increase the risk of influenza episodes in a cold climate.",2014 Mar 28,"['Jaakkola, Kari', 'Saukkoriipi, Annika', 'Jokelainen, Jari', 'Juvonen, Raija', 'Kauppila, Jaana', 'Vainio, Olli', 'Ziegler, Thedi', 'Rönkkö, Esa', 'Jaakkola, Jouni JK', 'Ikäheimo, Tiina M']",Environ Health,,,True
efaa556b484fbcd9cc34832ffac53ef3e834e9c0,PMC,Mucosal Vaccination with Recombinant Lactobacillus casei-Displayed CTA1-Conjugated Consensus Matrix Protein-2 (sM2) Induces Broad Protection against Divergent Influenza Subtypes in BALB/c Mice,http://dx.doi.org/10.1371/journal.pone.0094051,PMC3979752,24714362,CC BY,"To develop a safe and effective mucosal vaccine against pathogenic influenza viruses, we constructed recombinant Lactobacillus casei strains that express conserved matrix protein 2 with (pgsA-CTA1-sM2/L. casei) or without (pgsA-sM2/L. casei) cholera toxin subunit A1 (CTA1) on the surface. The surface localization of the fusion protein was verified by cellular fractionation analyses, flow cytometry and immunofluorescence microscopy. Oral and nasal inoculations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and mucosal IgA. However, the conjugation of cholera toxin subunit A1 induced more potent mucosal, humoral and cell-mediated immune responses. In a challenge test with 10 MLD(50) of A/EM/Korea/W149/06(H5N1), A/Puerto Rico/8/34(H1N1), A/Aquatic bird /Korea/W81/2005(H5N2), A/Aquatic bird/Korea/W44/2005(H7N3), and A/Chicken/Korea/116/2004(H9N2) viruses, the recombinant pgsA-CTA1-sM2/L. casei provided better protection against lethal challenges than pgsA-sM2/L. casei, pgsA/L. casei and PBS in mice. These results indicate that mucosal immunization with recombinant L. casei expressing CTA1-conjugated sM2 protein on its surface is an effective means of eliciting protective immune responses against diverse influenza subtypes.",2014 Apr 8,"['Chowdhury, Mohammed Y. E.', 'Li, Rui', 'Kim, Jae-Hoon', 'Park, Min-Eun', 'Kim, Tae-Hwan', 'Pathinayake, Prabuddha', 'Weeratunga, Prasanna', 'Song, Man Ki', 'Son, Hwa-Young', 'Hong, Seung-Pyo', 'Sung, Moon-Hee', 'Lee, Jong-Soo', 'Kim, Chul-Joong']",PLoS One,,,True
c6c0a0d35bdedb534df909619bd7f240f9d52ae6,PMC,The Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus Induces the Translocation of Protein Disulphide Isomerase-Like Oxidoreductases from the Endoplasmic Reticulum to the Cell Surface and the Extracellular Space,http://dx.doi.org/10.1371/journal.pone.0094656,PMC3979861,24714576,CC BY,"Nairobi sheep disease virus (NSDV) of the genus Nairovirus causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%; the virus is found in East and Central Africa, and in India, where the virus is called Ganjam virus. NSDV is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus, which also causes a haemorrhagic disease. As with other nairoviruses, replication of NSDV takes place in the cytoplasm and the new virus particles bud into the Golgi apparatus; however, the effect of viral replication on cellular compartments has not been studied extensively. We have found that the overall structure of the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment and the Golgi were unaffected by infection with NSDV. However, we observed that NSDV infection led to the loss of protein disulphide isomerase (PDI), an oxidoreductase present in the lumen of the endoplasmic reticulum (ER) and which assists during protein folding, from the ER. Further investigation showed that NSDV-infected cells have high levels of PDI at their surface, and PDI is also secreted into the culture medium of infected cells. Another chaperone from the PDI family, ERp57, was found to be similarly affected. Analysis of infected cells and expression of individual viral glycoproteins indicated that the NSDV PreGn glycoprotein is involved in redistribution of these soluble ER oxidoreductases. It has been suggested that extracellular PDI can activate integrins and tissue factor, which are involved respectively in pro-inflammatory responses and disseminated intravascular coagulation, both of which manifest in many viral haemorrhagic fevers. The discovery of enhanced PDI secretion from NSDV-infected cells may be an important finding for understanding the mechanisms underlying the pathogenicity of haemorrhagic nairoviruses.",2014 Apr 8,"['Lasecka, Lidia', 'Baron, Michael D.']",PLoS One,,,True
e0a2b2bc691434ef31983736806d4e558b222c92,PMC,The Regulation of Autophagy by Influenza A Virus,http://dx.doi.org/10.1155/2014/498083,PMC3980786,24779013,CC BY,"Influenza A virus is a dreadful pathogen of animals and humans, causing widespread infection and severe morbidity and mortality. It is essential to characterize the influenza A virus-host interaction and develop efficient counter measures against the viral infection. Autophagy is known as a catabolic process for the recycling of the cytoplasmic macromolecules. Recently, it has been shown that autophagy is a critical mechanism underlying the interaction between influenza A virus and its host. Autophagy can be induced by the infection with influenza A virus, which is considered as a necessary process for the viral proliferation, including the accumulation of viral elements during the replication of influenza A virus. On the other hand, influenza A virus can inhibit the autophagic formation via interaction with the autophagy-related genes (Atg) and signaling pathways. In addition, autophagy is involved in the influenza virus-regulated cell deaths, leading to significant changes in host apoptosis. Interestingly, the high pathogenic strains of influenza A virus, such as H5N1, stimulate autophagic cell death and appear to interplay with the autophagy in distinct ways as compared with low pathogenic strains. This review discusses the regulation of autophagy, an influenza A virus driven process.",2014 Mar 23,"['Zhang, Rong', 'Chi, Xiaojuan', 'Wang, Song', 'Qi, Baomin', 'Yu, Xiaoqiang', 'Chen, Ji-Long']",Biomed Res Int,,,True
0089aa4b17549b9774f13a9e2e12a84fc827d60b,PMC,The Domain-Specific and Temperature-Dependent Protein Misfolding Phenotype of Variant Medium-Chain acyl-CoA Dehydrogenase,http://dx.doi.org/10.1371/journal.pone.0093852,PMC3981736,24718418,CC BY,"The implementation of expanded newborn screening programs reduced mortality and morbidity in medium-chain acyl-CoA dehydrogenase deficiency (MCADD) caused by mutations in the ACADM gene. However, the disease is still potentially fatal. Missense induced MCADD is a protein misfolding disease with a molecular loss-of-function phenotype. Here we established a comprehensive experimental setup to analyze the structural consequences of eight ACADM missense mutations (p.Ala52Val, p.Tyr67His, p.Tyr158His, p.Arg206Cys, p.Asp266Gly, p.Lys329Glu, p.Arg334Lys, p.Arg413Ser) identified after newborn screening and linked the corresponding protein misfolding phenotype to the site of side-chain replacement with respect to the domain. With fever being the crucial risk factor for metabolic decompensation of patients with MCADD, special emphasis was put on the analysis of structural and functional derangements related to thermal stress. Based on protein conformation, thermal stability and kinetic stability, the molecular phenotype in MCADD depends on the structural region that is affected by missense-induced conformational changes with the central β-domain being particularly prone to structural derangement and destabilization. Since systematic classification of conformational derangements induced by ACADM mutations may be a helpful tool in assessing the clinical risk of patients, we scored the misfolding phenotype of the variants in comparison to p.Lys329Glu (K304E), the classical severe mutation, and p.Tyr67His (Y42H), discussed to be mild. Experiments assessing the impact of thermal stress revealed that mutations in the ACADM gene lower the temperature threshold at which MCAD loss-of-function occurs. Consequently, increased temperature as it occurs during intercurrent infections, significantly increases the risk of further conformational derangement and loss of function of the MCAD enzyme explaining the life-threatening clinical courses observed during fever episodes. Early and aggressive antipyretic treatment thus may be life-saving in patients suffering from MCADD.",2014 Apr 9,"['Jank, Johanna M.', 'Maier, Esther M.', 'Reiß, Dunja D.', 'Haslbeck, Martin', 'Kemter, Kristina F.', 'Truger, Marietta S.', 'Sommerhoff, Christian P.', 'Ferdinandusse, Sacha', 'Wanders, Ronald J.', 'Gersting, Søren W.', 'Muntau, Ania C.']",PLoS One,,,True
faad09d0c4532ac11d673b84f539be583e897df9,PMC,The Spatial Resolution of Epidemic Peaks,http://dx.doi.org/10.1371/journal.pcbi.1003561,PMC3983068,24722420,CC BY,"The emergence of novel respiratory pathogens can challenge the capacity of key health care resources, such as intensive care units, that are constrained to serve only specific geographical populations. An ability to predict the magnitude and timing of peak incidence at the scale of a single large population would help to accurately assess the value of interventions designed to reduce that peak. However, current disease-dynamic theory does not provide a clear understanding of the relationship between: epidemic trajectories at the scale of interest (e.g. city); population mobility; and higher resolution spatial effects (e.g. transmission within small neighbourhoods). Here, we used a spatially-explicit stochastic meta-population model of arbitrary spatial resolution to determine the effect of resolution on model-derived epidemic trajectories. We simulated an influenza-like pathogen spreading across theoretical and actual population densities and varied our assumptions about mobility using Latin-Hypercube sampling. Even though, by design, cumulative attack rates were the same for all resolutions and mobilities, peak incidences were different. Clear thresholds existed for all tested populations, such that models with resolutions lower than the threshold substantially overestimated population-wide peak incidence. The effect of resolution was most important in populations which were of lower density and lower mobility. With the expectation of accurate spatial incidence datasets in the near future, our objective was to provide a framework for how to use these data correctly in a spatial meta-population model. Our results suggest that there is a fundamental spatial resolution for any pathogen-population pair. If underlying interactions between pathogens and spatially heterogeneous populations are represented at this resolution or higher, accurate predictions of peak incidence for city-scale epidemics are feasible.",2014 Apr 10,"['Mills, Harriet L.', 'Riley, Steven']",PLoS Comput Biol,,,True
0d71c6368927c7235b7ab328d1ee33aebe699396,PMC,The Spatial Resolution of Epidemic Peaks,http://dx.doi.org/10.1371/journal.pcbi.1003561,PMC3983068,24722420,CC BY,"The emergence of novel respiratory pathogens can challenge the capacity of key health care resources, such as intensive care units, that are constrained to serve only specific geographical populations. An ability to predict the magnitude and timing of peak incidence at the scale of a single large population would help to accurately assess the value of interventions designed to reduce that peak. However, current disease-dynamic theory does not provide a clear understanding of the relationship between: epidemic trajectories at the scale of interest (e.g. city); population mobility; and higher resolution spatial effects (e.g. transmission within small neighbourhoods). Here, we used a spatially-explicit stochastic meta-population model of arbitrary spatial resolution to determine the effect of resolution on model-derived epidemic trajectories. We simulated an influenza-like pathogen spreading across theoretical and actual population densities and varied our assumptions about mobility using Latin-Hypercube sampling. Even though, by design, cumulative attack rates were the same for all resolutions and mobilities, peak incidences were different. Clear thresholds existed for all tested populations, such that models with resolutions lower than the threshold substantially overestimated population-wide peak incidence. The effect of resolution was most important in populations which were of lower density and lower mobility. With the expectation of accurate spatial incidence datasets in the near future, our objective was to provide a framework for how to use these data correctly in a spatial meta-population model. Our results suggest that there is a fundamental spatial resolution for any pathogen-population pair. If underlying interactions between pathogens and spatially heterogeneous populations are represented at this resolution or higher, accurate predictions of peak incidence for city-scale epidemics are feasible.",2014 Apr 10,"['Mills, Harriet L.', 'Riley, Steven']",PLoS Comput Biol,,,False
ce5e67e3d17645302f7a91d7d0c8bc3428884187,PMC,The Spatial Resolution of Epidemic Peaks,http://dx.doi.org/10.1371/journal.pcbi.1003561,PMC3983068,24722420,CC BY,"The emergence of novel respiratory pathogens can challenge the capacity of key health care resources, such as intensive care units, that are constrained to serve only specific geographical populations. An ability to predict the magnitude and timing of peak incidence at the scale of a single large population would help to accurately assess the value of interventions designed to reduce that peak. However, current disease-dynamic theory does not provide a clear understanding of the relationship between: epidemic trajectories at the scale of interest (e.g. city); population mobility; and higher resolution spatial effects (e.g. transmission within small neighbourhoods). Here, we used a spatially-explicit stochastic meta-population model of arbitrary spatial resolution to determine the effect of resolution on model-derived epidemic trajectories. We simulated an influenza-like pathogen spreading across theoretical and actual population densities and varied our assumptions about mobility using Latin-Hypercube sampling. Even though, by design, cumulative attack rates were the same for all resolutions and mobilities, peak incidences were different. Clear thresholds existed for all tested populations, such that models with resolutions lower than the threshold substantially overestimated population-wide peak incidence. The effect of resolution was most important in populations which were of lower density and lower mobility. With the expectation of accurate spatial incidence datasets in the near future, our objective was to provide a framework for how to use these data correctly in a spatial meta-population model. Our results suggest that there is a fundamental spatial resolution for any pathogen-population pair. If underlying interactions between pathogens and spatially heterogeneous populations are represented at this resolution or higher, accurate predictions of peak incidence for city-scale epidemics are feasible.",2014 Apr 10,"['Mills, Harriet L.', 'Riley, Steven']",PLoS Comput Biol,,,True
aa8fbab7c3255083bf78bcf8752b279ec210e684,PMC,The Spatial Resolution of Epidemic Peaks,http://dx.doi.org/10.1371/journal.pcbi.1003561,PMC3983068,24722420,CC BY,"The emergence of novel respiratory pathogens can challenge the capacity of key health care resources, such as intensive care units, that are constrained to serve only specific geographical populations. An ability to predict the magnitude and timing of peak incidence at the scale of a single large population would help to accurately assess the value of interventions designed to reduce that peak. However, current disease-dynamic theory does not provide a clear understanding of the relationship between: epidemic trajectories at the scale of interest (e.g. city); population mobility; and higher resolution spatial effects (e.g. transmission within small neighbourhoods). Here, we used a spatially-explicit stochastic meta-population model of arbitrary spatial resolution to determine the effect of resolution on model-derived epidemic trajectories. We simulated an influenza-like pathogen spreading across theoretical and actual population densities and varied our assumptions about mobility using Latin-Hypercube sampling. Even though, by design, cumulative attack rates were the same for all resolutions and mobilities, peak incidences were different. Clear thresholds existed for all tested populations, such that models with resolutions lower than the threshold substantially overestimated population-wide peak incidence. The effect of resolution was most important in populations which were of lower density and lower mobility. With the expectation of accurate spatial incidence datasets in the near future, our objective was to provide a framework for how to use these data correctly in a spatial meta-population model. Our results suggest that there is a fundamental spatial resolution for any pathogen-population pair. If underlying interactions between pathogens and spatially heterogeneous populations are represented at this resolution or higher, accurate predictions of peak incidence for city-scale epidemics are feasible.",2014 Apr 10,"['Mills, Harriet L.', 'Riley, Steven']",PLoS Comput Biol,,,True
91ff06254beef1b03a35520d4fd5bad025274b08,PMC,The Spatial Resolution of Epidemic Peaks,http://dx.doi.org/10.1371/journal.pcbi.1003561,PMC3983068,24722420,CC BY,"The emergence of novel respiratory pathogens can challenge the capacity of key health care resources, such as intensive care units, that are constrained to serve only specific geographical populations. An ability to predict the magnitude and timing of peak incidence at the scale of a single large population would help to accurately assess the value of interventions designed to reduce that peak. However, current disease-dynamic theory does not provide a clear understanding of the relationship between: epidemic trajectories at the scale of interest (e.g. city); population mobility; and higher resolution spatial effects (e.g. transmission within small neighbourhoods). Here, we used a spatially-explicit stochastic meta-population model of arbitrary spatial resolution to determine the effect of resolution on model-derived epidemic trajectories. We simulated an influenza-like pathogen spreading across theoretical and actual population densities and varied our assumptions about mobility using Latin-Hypercube sampling. Even though, by design, cumulative attack rates were the same for all resolutions and mobilities, peak incidences were different. Clear thresholds existed for all tested populations, such that models with resolutions lower than the threshold substantially overestimated population-wide peak incidence. The effect of resolution was most important in populations which were of lower density and lower mobility. With the expectation of accurate spatial incidence datasets in the near future, our objective was to provide a framework for how to use these data correctly in a spatial meta-population model. Our results suggest that there is a fundamental spatial resolution for any pathogen-population pair. If underlying interactions between pathogens and spatially heterogeneous populations are represented at this resolution or higher, accurate predictions of peak incidence for city-scale epidemics are feasible.",2014 Apr 10,"['Mills, Harriet L.', 'Riley, Steven']",PLoS Comput Biol,,,False
e572a3a154399f2b500b0f547a7252c94580acf4,PMC,Prediction of High Incidence of Dengue in the Philippines,http://dx.doi.org/10.1371/journal.pntd.0002771,PMC3983113,24722434,CC0,"BACKGROUND: Accurate prediction of dengue incidence levels weeks in advance of an outbreak may reduce the morbidity and mortality associated with this neglected disease. Therefore, models were developed to predict high and low dengue incidence in order to provide timely forewarnings in the Philippines. METHODS: Model inputs were chosen based on studies indicating variables that may impact dengue incidence. The method first uses Fuzzy Association Rule Mining techniques to extract association rules from these historical epidemiological, environmental, and socio-economic data, as well as climate data indicating future weather patterns. Selection criteria were used to choose a subset of these rules for a classifier, thereby generating a Prediction Model. The models predicted high or low incidence of dengue in a Philippines province four weeks in advance. The threshold between high and low was determined relative to historical incidence data. PRINCIPAL FINDINGS: Model accuracy is described by Positive Predictive Value (PPV), Negative Predictive Value (NPV), Sensitivity, and Specificity computed on test data not previously used to develop the model. Selecting a model using the F(0.5) measure, which gives PPV more importance than Sensitivity, gave these results: PPV = 0.780, NPV = 0.938, Sensitivity = 0.547, Specificity = 0.978. Using the F(3) measure, which gives Sensitivity more importance than PPV, the selected model had PPV = 0.778, NPV = 0.948, Sensitivity = 0.627, Specificity = 0.974. The decision as to which model has greater utility depends on how the predictions will be used in a particular situation. CONCLUSIONS: This method builds prediction models for future dengue incidence in the Philippines and is capable of being modified for use in different situations; for diseases other than dengue; and for regions beyond the Philippines. The Philippines dengue prediction models predicted high or low incidence of dengue four weeks in advance of an outbreak with high accuracy, as measured by PPV, NPV, Sensitivity, and Specificity.",2014 Apr 10,"['Buczak, Anna L.', 'Baugher, Benjamin', 'Babin, Steven M.', 'Ramac-Thomas, Liane C.', 'Guven, Erhan', 'Elbert, Yevgeniy', 'Koshute, Phillip T.', 'Velasco, John Mark S.', 'Roque, Vito G.', 'Tayag, Enrique A.', 'Yoon, In-Kyu', 'Lewis, Sheri H.']",PLoS Negl Trop Dis,,,True
b60f35d40ea356d450ec485223083150e662b10f,PMC,"Complete Genome Sequence of Strain SDCV/USA/Illinois121/2014, a Porcine Deltacoronavirus from the United States",http://dx.doi.org/10.1128/genomeA.00218-14,PMC3983293,24723704,CC BY,"To investigate the causative agent of swine diarrhea, next-generation sequencing (NGS) was performed on a porcine fecal sample. The NGS reads were assembled, which generated a complete swine Deltacoronavirus genome sequence, that of strain SDCV/USA/Illinois121/2014.",2014 Apr 10,"['Marthaler, Douglas', 'Jiang, Yin', 'Collins, Jim', 'Rossow, Kurt']",Genome Announc,,,True
4ebdb50f487a8f6c2421e3e3281b053990cb4fac,PMC,Full-Length Genome Sequence of Porcine Deltacoronavirus Strain USA/IA/2014/8734,http://dx.doi.org/10.1128/genomeA.00278-14,PMC3983307,24723718,CC BY,Porcine deltacoronavirus (PDCoV) was detected in feces from diarrheic sows during an epidemic of acute and transmissible diarrhea. No transmissible gastroenteritis virus or porcine epidemic diarrhea virus was detected. The PDCoV USA/IA/2014/8734 from the herd was sequenced for full-length genomic RNA to further characterize PDCoV in U.S. swine.,2014 Apr 10,"['Li, Ganwu', 'Chen, Qi', 'Harmon, Karen M.', 'Yoon, Kyoung-Jin', 'Schwartz, Kent J.', 'Hoogland, Marlin J.', 'Gauger, Phillip C.', 'Main, Rodger G.', 'Zhang, Jianqiang']",Genome Announc,,,True
c848bce30b9e60bccfd15a5534af1d0cea54c686,PMC,Thrombocytopenia Is Associated with Acute Respiratory Distress Syndrome Mortality: An International Study,http://dx.doi.org/10.1371/journal.pone.0094124,PMC3986053,24732309,CC BY,"BACKGROUND: Early detection of the Acute Respiratory Distress Syndrome (ARDS) has the potential to improvethe prognosis of critically ill patients admitted to the intensive care unit (ICU). However, no reliable biomarkers are currently available for accurate early detection of ARDS in patients with predisposing conditions. OBJECTIVES: This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies. METHODS: We examined clinical risk factors for ARDS in a cohort of 178 patients in Beijing, China who were admitted to the ICU and were at high risk for ARDS. Identified biomarkers were then replicated in a second cohort of1,878 patients in Boston, USA. RESULTS: Of 178 patients recruited from participating hospitals in Beijing, 75 developed ARDS. After multivariate adjustment, sepsis (odds ratio [OR]:5.58, 95% CI: 1.70–18.3), pulmonary injury (OR: 3.22; 95% CI: 1.60–6.47), and thrombocytopenia, defined as platelet count <80×10(3)/µL, (OR: 2.67; 95% CI: 1.27–5.62)were significantly associated with increased risk of developing ARDS. Thrombocytopenia was also associated with increased mortality in patients who developed ARDS (adjusted hazard ratio [AHR]: 1.38, 95% CI: 1.07–1.57) but not in those who did not develop ARDS(AHR: 1.25, 95% CI: 0.96–1.62). The presence of both thrombocytopenia and ARDS substantially increased 60-daymortality. Sensitivity analyses showed that a platelet count of <100×10(3)/µLin combination with ARDS provide the highest prognostic value for mortality. These associations were replicated in the cohort of US patients. CONCLUSIONS: This study of ICU patients in both China and US showed that thrombocytopenia is associated with an increased risk of ARDS and platelet count in combination with ARDS had a high predictive value for patient mortality.",2014 Apr 14,"['Wang, Tiehua', 'Liu, Zhuang', 'Wang, Zhaoxi', 'Duan, Meili', 'Li, Gang', 'Wang, Shupeng', 'Li, Wenxiong', 'Zhu, Zhaozhong', 'Wei, Yongyue', 'Christiani, David C.', 'Li, Ang', 'Zhu, Xi']",PLoS One,,,True
bd592988022fb91de64e0d4c287d3b04d864f8ba,PMC,Advantages and Limitations of Anticipating Laboratory Test Results from Regression- and Tree-Based Rules Derived from Electronic Health-Record Data,http://dx.doi.org/10.1371/journal.pone.0092199,PMC3986061,24732572,CC BY,"Laboratory testing is the single highest-volume medical activity, making it useful to ask how well one can anticipate whether a given test result will be high, low, or within the reference interval (“normal”). We analyzed 10 years of electronic health records—a total of 69.4 million blood tests—to see how well standard rule-mining techniques can anticipate test results based on patient age and gender, recent diagnoses, and recent laboratory test results. We evaluated rules according to their positive and negative predictive value (PPV and NPV) and area under the receiver-operator characteristic curve (ROC AUCs). Using a stringent cutoff of PPV and/or NPV≥0.95, standard techniques yield few rules for sendout tests but several for in-house tests, mostly for repeat laboratory tests that are part of the complete blood count and basic metabolic panel. Most rules were clinically and pathophysiologically plausible, and several seemed clinically useful for informing pre-test probability of a given result. But overall, rules were unlikely to be able to function as a general substitute for actually ordering a test. Improving laboratory utilization will likely require different input data and/or alternative methods.",2014 Apr 14,"['Mohammad, Fahim', 'Theisen-Toupal, Jesse C.', 'Arnaout, Ramy']",PLoS One,,,True
90706dd8b172f0aeb996ea828c356155c32e0682,PMC,"Anxiety, worry and cognitive risk estimate in relation to protective behaviors during the 2009 influenza A/H1N1 pandemic in Hong Kong: ten cross-sectional surveys",http://dx.doi.org/10.1186/1471-2334-14-169,PMC3986671,24674239,CC BY,"BACKGROUND: Few studies have investigated associations between psychological and behavioral indices throughout a major epidemic. This study was aimed to compare the strength of associations between different cognitive and affective measures of risk and self-reported protective behaviors in a series of ten cross-sectional surveys conducted throughout the first wave of influenza A/H1N1 pandemic. METHODS: All surveys were conducted using questionnaire-based telephone interviews, with random digit dialing to recruit adults from the general population. Measures of anxiety and worry (affective) and perceived risk (cognitive) regarding A/H1N1 were made in 10 serial surveys. Multivariate logistic regression models were used to estimate the cognitive/affective-behavioral associations in each survey while multilevel logistic models were conducted to estimate the average effects of each cognitive/affective measure on adoption of protective behaviors throughout the ten surveys. RESULTS: Excepting state anxiety, other affective measures including “anticipated worry”, “experienced worry” and “current worry” specific to A/H1N1 risk were consistently and strongly associated with adoption of protective behaviors across different survey periods. However, the cognitive-behavioral associations were weaker and inconsistent across the ten surveys. Perceived A/H1N1 severity relative to SARS had stronger associations with adoption of protective behaviors in the late epidemic periods than in the early epidemic periods. CONCLUSION: Risk-specific worries appear to be significantly associated with the adoption of protective behaviors at different epidemic stages, whereas cognitive measures may become more important in understanding people’s behavioral responses later in epidemics. Future epidemic-related psycho-behavioral research should include more affective-loaded measures of risk.",2014 Mar 27,"['Liao, Qiuyan', 'Cowling, Benjamin J', 'Lam, Wendy WT', 'Ng, Diane MW', 'Fielding, Richard']",BMC Infect Dis,,,True
b3f4cd3e21b32b677d50fda144e8eed9ee44df8e,PMC,High-dose dietary zinc oxide mitigates infection with transmissible gastroenteritis virus in piglets,http://dx.doi.org/10.1186/1746-6148-10-75,PMC3986850,24673930,CC BY,"BACKGROUND: Zinc (Zn) supplementation has been shown to reduce the incidence of diarrhea and to protect animals from intestinal diseases, but the mechanisms of this protective effect against virus infection in vivo have not yet been elucidated. Transmissible gastroenteritis virus (TGEV) causes diarrhea in piglets with an age-dependent decrease of severity. RESULTS: We used 60 weaned piglets that were divided into three groups to evaluate the effect of different Zn levels added to a conventional diet (50 mg Zn/kg diet, Zn(low), control group). The other groups received the diet supplemented with ZnO at final concentrations of 150 mg Zn/kg diet (Zn(med)), or 2,500 mg/kg diet (Zn(high)). Oral challenge infection with TGEV was performed when the pigs had been fed for 1 week with the respective diet. Half of the piglets of each group were sacrificed at day 1 and 18 after challenge infection. Fecal consistency was improved and body weights increased in the Zn(high) group when compared to the other groups, but no direct effect of Zn concentrations in the diet on fecal TGEV shedding and mucosal immune responses was detectable. However, in the Zn(high) group, we found a prevention of villus atrophy and decreased caspase-3-mediated apoptosis of jejunal epithelium. Furthermore, pigs receiving high Zn diet showed a down-regulation of interferon (IFN)-α, oligoadenylate synthetase (OAS), Zn transporter SLC39A4 (ZIP4), but up-regulation of metallothionein-1 (MT1), as well as the Zn transporters SLC30A1 (ZnT1) and SLC30A5 (ZnT5). In addition, forskolin-induced chloride secretion and epithelial resistance were controlled at a physiological level in the Zn(high) but not the other groups. Finally, in the Zn(high) group, we documented an earlier and higher systemic TGEV-specific serum antibody response. CONCLUSIONS: These results suggest that high dietary Zn could provide enhanced protection in the intestinal tract and stimulate the systemic humoral immune response against TGEV infection.",2014 Mar 28,"['Chai, Weidong', 'Zakrzewski, Silke S', 'Günzel, Dorothee', 'Pieper, Robert', 'Wang, Zhenya', 'Twardziok, Sven', 'Janczyk, Pawel', 'Osterrieder, Nikolaus', 'Burwinkel, Michael']",BMC Vet Res,,,True
9faf6a32a170b3fc5950af6a7d34cf710c79321d,PMC,"Gene silencing of β-galactosamide α-2,6-sialyltransferase 1 inhibits human influenza virus infection of airway epithelial cells",http://dx.doi.org/10.1186/1471-2180-14-78,PMC3986885,24670114,CC BY,"BACKGROUND: Human influenza virus hemagglutinin prefers to use sialic acid (SA) receptors via α-2,6 linkages. The β-galactoside α-2,6-sialyltransferase I (ST6Gal I) protein is encoded by the ST6GAL1 gene and is responsible for the addition of α-2,6 linked SA to the Galβ1-4GlcNAc disaccharide of glycans and glycoproteins found on the cellular surface. Therefore, ST6GAL1 could be a potential target for anti-influenza therapeutics. We used specific small interfering RNAs (siRNAs) to block expression of ST6GAL1 and limit distribution of SA receptors on the surface of airway epithelial cells. RESULTS: The siRNA duplexes we used inhibited ST6GAL1 mRNA expression and subsequent expression of the encoding protein. As a result, synthesis of α-2,6 SA galactose was inhibited. Adsorption of influenza virus particles to the surface of cells transfected with appropriate specific siRNAs was significantly reduced. Intracellular viral genome copy number and virus titer within the supernatant of cells transfected with siRNAs was significantly reduced in a dose-dependent manner compared with those for untransfected cells and cells transfected with non-specific siRNAs. CONCLUSIONS: We used siRNAs targeting ST6GAL1 to inhibit the expression of certain cell surface receptors, thereby preventing virus adsorption. This resulted in the inhibition of human influenza virus infection. Our findings are a significant development in the identification of potential new anti-influenza drug targets.",2014 Mar 27,"['Wu, Dong', 'Huang, Wenbo', 'Wang, Yutao', 'Guan, Wenda', 'Li, Runfeng', 'Yang, Zifeng', 'Zhong, Nanshan']",BMC Microbiol,,,True
b675d6df1216305b9f778bb8e8f9701fa3ff5ca9,PMC,"Gene silencing of β-galactosamide α-2,6-sialyltransferase 1 inhibits human influenza virus infection of airway epithelial cells",http://dx.doi.org/10.1186/1471-2180-14-78,PMC3986885,24670114,CC BY,"BACKGROUND: Human influenza virus hemagglutinin prefers to use sialic acid (SA) receptors via α-2,6 linkages. The β-galactoside α-2,6-sialyltransferase I (ST6Gal I) protein is encoded by the ST6GAL1 gene and is responsible for the addition of α-2,6 linked SA to the Galβ1-4GlcNAc disaccharide of glycans and glycoproteins found on the cellular surface. Therefore, ST6GAL1 could be a potential target for anti-influenza therapeutics. We used specific small interfering RNAs (siRNAs) to block expression of ST6GAL1 and limit distribution of SA receptors on the surface of airway epithelial cells. RESULTS: The siRNA duplexes we used inhibited ST6GAL1 mRNA expression and subsequent expression of the encoding protein. As a result, synthesis of α-2,6 SA galactose was inhibited. Adsorption of influenza virus particles to the surface of cells transfected with appropriate specific siRNAs was significantly reduced. Intracellular viral genome copy number and virus titer within the supernatant of cells transfected with siRNAs was significantly reduced in a dose-dependent manner compared with those for untransfected cells and cells transfected with non-specific siRNAs. CONCLUSIONS: We used siRNAs targeting ST6GAL1 to inhibit the expression of certain cell surface receptors, thereby preventing virus adsorption. This resulted in the inhibition of human influenza virus infection. Our findings are a significant development in the identification of potential new anti-influenza drug targets.",2014 Mar 27,"['Wu, Dong', 'Huang, Wenbo', 'Wang, Yutao', 'Guan, Wenda', 'Li, Runfeng', 'Yang, Zifeng', 'Zhong, Nanshan']",BMC Microbiol,,,False
d5f9caf3c407fae4690cd853b95d3c3e9b0a8b5e,PMC,"Disaster resilience in tertiary hospitals: a cross-sectional survey in Shandong Province, China",http://dx.doi.org/10.1186/1472-6963-14-135,PMC3987831,24661641,CC BY,"BACKGROUND: Hospital disaster resilience can be defined as a hospital’s ability to resist, absorb, and respond to the shock of disasters while maintaining critical functions, and then to recover to its original state or adapt to a new one. This study aims to explore the status of resilience among tertiary hospitals in Shandong Province, China. METHODS: A stratified random sample (n = 50) was derived from tertiary A, tertiary B, and tertiary C hospitals in Shandong Province, and was surveyed by questionnaire. Data on hospital characteristics and 8 key domains of hospital resilience were collected and analysed. Variables were binary, and analysed using descriptive statistics such as frequencies. RESULTS: A response rate of 82% (n = 41) was attained. Factor analysis identified four key factors from eight domains which appear to reflect the overall level of disaster resilience. These were hospital safety, disaster management mechanisms, disaster resources and disaster medical care capability. The survey demonstrated that in regard to hospital safety, 93% had syndromic surveillance systems for infectious diseases and 68% had evaluated their safety standards. In regard to disaster management mechanisms, all had general plans, while only 20% had specific plans for individual hazards. 49% had a public communication protocol and 43.9% attended the local coordination meetings. In regard to disaster resources, 75.6% and 87.5% stockpiled emergency drugs and materials respectively, while less than a third (30%) had a signed Memorandum of Understanding with other hospitals to share these resources. Finally in regard to medical care, 66% could dispatch an on-site medical rescue team, but only 5% had a ‘portable hospital’ function and 36.6% and 12% of the hospitals could surge their beds and staff capacity respectively. The average beds surge capacity within 1 day was 13%. CONCLUSIONS: This study validated the broad utility of a framework for understanding and measuring the level of hospital resilience. The survey demonstrated considerable variability in disaster resilience arrangements of tertiary hospitals in Shandong province, and the difference between tertiary A hospitals and tertiary B hospitals was also identified in essential areas.",2014 Mar 25,"['Zhong, Shuang', 'Hou, Xiang-Yu', 'Clark, Michele', 'Zang, Yu-Li', 'Wang, Lu', 'Xu, Ling-Zhong', 'FitzGerald, Gerard']",BMC Health Serv Res,,,True
4f2c063485df91923fc9c7c9f4ec6ebf5a61157a,PMC,"Model for Vaccine Design by Prediction of B-Epitopes of IEDB Given Perturbations in Peptide Sequence, In Vivo Process, Experimental Techniques, and Source or Host Organisms",http://dx.doi.org/10.1155/2014/768515,PMC3987976,24741624,CC BY,"Perturbation methods add variation terms to a known experimental solution of one problem to approach a solution for a related problem without known exact solution. One problem of this type in immunology is the prediction of the possible action of epitope of one peptide after a perturbation or variation in the structure of a known peptide and/or other boundary conditions (host organism, biological process, and experimental assay). However, to the best of our knowledge, there are no reports of general-purpose perturbation models to solve this problem. In a recent work, we introduced a new quantitative structure-property relationship theory for the study of perturbations in complex biomolecular systems. In this work, we developed the first model able to classify more than 200,000 cases of perturbations with accuracy, sensitivity, and specificity >90% both in training and validation series. The perturbations include structural changes in >50000 peptides determined in experimental assays with boundary conditions involving >500 source organisms, >50 host organisms, >10 biological process, and >30 experimental techniques. The model may be useful for the prediction of new epitopes or the optimization of known peptides towards computational vaccine design.",2014 Jan 12,"['González-Díaz, Humberto', 'Pérez-Montoto, Lázaro G.', 'Ubeira, Florencio M.']",J Immunol Res,,,False
a0f4a467be80972f434dabf027d2b5260b608740,PMC,"Model for Vaccine Design by Prediction of B-Epitopes of IEDB Given Perturbations in Peptide Sequence, In Vivo Process, Experimental Techniques, and Source or Host Organisms",http://dx.doi.org/10.1155/2014/768515,PMC3987976,24741624,CC BY,"Perturbation methods add variation terms to a known experimental solution of one problem to approach a solution for a related problem without known exact solution. One problem of this type in immunology is the prediction of the possible action of epitope of one peptide after a perturbation or variation in the structure of a known peptide and/or other boundary conditions (host organism, biological process, and experimental assay). However, to the best of our knowledge, there are no reports of general-purpose perturbation models to solve this problem. In a recent work, we introduced a new quantitative structure-property relationship theory for the study of perturbations in complex biomolecular systems. In this work, we developed the first model able to classify more than 200,000 cases of perturbations with accuracy, sensitivity, and specificity >90% both in training and validation series. The perturbations include structural changes in >50000 peptides determined in experimental assays with boundary conditions involving >500 source organisms, >50 host organisms, >10 biological process, and >30 experimental techniques. The model may be useful for the prediction of new epitopes or the optimization of known peptides towards computational vaccine design.",2014 Jan 12,"['González-Díaz, Humberto', 'Pérez-Montoto, Lázaro G.', 'Ubeira, Florencio M.']",J Immunol Res,,,True
900f9612d2b06b3e32f4d460305a282d259f370d,PMC,Comparison of DNA-Hydrolyzing Antibodies from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis,http://dx.doi.org/10.1371/journal.pone.0093001,PMC3988009,24736683,CC BY,"It was found that high-affinity anti-DNA antibodies were one of the major components of the intrathecal IgG response in multiple sclerosis (MS) patients [Williamson et al., PNAS, 2001]. Recently we have shown that IgGs from the sera of MS patients are active in the hydrolysis of DNA. Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients. The relative activities of total protein from sera and CSFs varied remarkably from patient to patient. It was surprising that the specific DNase activity of the total protein of CSF reparations were 198-fold higher than the serum ones. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ∼49-fold higher than that from the sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that DNase IgGs of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and MS pathogenesis development.",2014 Apr 15,"['Parkhomenko, Taisiya A.', 'Doronin, Vasilii B.', 'Castellazzi, Massimiliano', 'Padroni, Marina', 'Pastore, Michela', 'Buneva, Valentina N.', 'Granieri, Enrico', 'Nevinsky, Georgy A.']",PLoS One,,,True
d4190432c724cc90504db6a90053c0a61057eb7c,PMC,"Detection of the Influenza A(H1N1)pdm09 Virus Carrying the K-15E, P83S and Q293H Mutations in Patients Who Have Undergone Bone Marrow Transplant",http://dx.doi.org/10.1371/journal.pone.0094822,PMC3989246,24740088,CC BY,"The 2009 pandemic influenza A(H1N1)pdm09 virus emerged and caused considerable morbidity and mortality in the third world, especially in Brazil. Although circulating strains of A(H1N1)pdm09 are A/California/04/2009-like (CA-04-like) viruses, various studies have suggested that some mutations in the viral hemagglutinin (HA) may be associated with enhanced severity and fatality. This phenomenon is particularly challenging for immunocompromised individuals, such as those who have undergone bone marrow transplant (BMT), because they are more likely to display worse clinical outcomes to influenza infection than non-immunocompromised individuals. We studied the clinical and viral aspects of post-BMT patients with confirmed A(H1N1)pdm09 diagnosis in the largest cancer hospital in Brazil. We found a viral strain with K-15E, P83S and Q293H polymorphisms in the HA, which is presumably more virulent, in these individuals. Despite that, these patients showed only mild symptoms of infection. Our findings complement the discovery of mild cases of infection with the A(H1N1)pdm09 virus with the K-15E, P83S and Q293H mutations in Brazil and oppose other studies that have linked these changes with increased disease severity. These results could be important for a better comprehension of the impact of the pandemic influenza in the context of BMT.",2014 Apr 16,"['Mesquita, Milene', 'Resende, Paola', 'Marttorelli, Andressa', 'Machado, Viviane', 'Sacramento, Carolina Q.', 'Fintelman-Rodrigues, Natalia', 'Abrantes, Juliana L.', 'Tavares, Rita', 'Schirmer, Marcelo', 'Siqueira, Marilda M.', 'Souza, Thiago Moreno L.']",PLoS One,,,True
e782e045471faad6e0a63dae1f064e345d754493,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,True
c21d33b3490e3e6d79a368346f37459d7b400dd7,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,False
2c6ed53ad8928f5004e26f4c8312623b6e9c8b28,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,False
b1350b65c323c618c3b688f68922699725242ff9,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,False
bc40cb8cb2e3be7d265ec142561efed182e9fd50,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,False
5f5149411e4a10a325d6369bb27d3a24d0b0a801,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,False
ab32facb1031aea8f1a2b8b5be3d3d20077388d5,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,False
a5b5be924639d6af104435ff9f67fbefc4236fb6,PMC,Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0095322,PMC3989284,24740153,CC BY,"Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.",2014 Apr 16,"Kikhno, Irina",PLoS One,,,False
6dbe5c842f58c1846c7659a0fb4f0da62d137c73,PMC,Counteraction of the multifunctional restriction factor tetherin,http://dx.doi.org/10.3389/fmicb.2014.00163,PMC3989765,24782851,CC BY,"The interferon-inducible restriction factor tetherin (also known as CD317, BST-2 or HM1.24) has emerged as a key component of the antiviral immune response. Initially, tetherin was shown to restrict replication of various enveloped viruses by inhibiting the release of budding virions from infected cells. More recently, it has become clear that tetherin also acts as a pattern recognition receptor inducing NF-κB-dependent proinflammatory gene expression in virus infected cells. Whereas the ability to restrict virion release is highly conserved among mammalian tetherin orthologs and thus probably an ancient function of this protein, innate sensing seems to be an evolutionarily recent activity. The potent and broad antiviral activity of tetherin is reflected by the fact that many viruses evolved means to counteract this restriction factor. A continuous arms race with viruses has apparently driven the evolution of different isoforms of tetherin with different functional properties. Interestingly, tetherin has also been implicated in cellular processes that are unrelated to immunity, such as the organization of the apical actin network and membrane microdomains or stabilization of the Golgi apparatus. In this review, I summarize our current knowledge of the different functions of tetherin and describe the molecular strategies that viruses have evolved to antagonize or evade this multifunctional host restriction factor.",2014 Apr 10,"Sauter, Daniel",Front Microbiol,,,True
5534fcf5c7e7df182da3c253d2312cd5662259b8,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,True
479da48b0ba5eadbcf457e609adfe701fba6f27a,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,False
4f2cd9ec8eed6fe97d78e1893dc0801604347e00,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,False
f5872038f326d5b93192fb1aebd5896624506310,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,False
8dd5e7afcdb1235f5b6241ebe79d22fc66e61ddf,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,False
483953cef653fdfa80fdce8e38788f2d503e5a72,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,False
80e5844199de5f7719dd366b92b5b90aa9e4f81e,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,False
387ef042d74eed570e829ad4b9d7b721cfc9ea27,PMC,The Expanding Functions of Cellular Helicases: The Tombusvirus RNA Replication Enhancer Co-opts the Plant eIF4AIII-Like AtRH2 and the DDX5-Like AtRH5 DEAD-Box RNA Helicases to Promote Viral Asymmetric RNA Replication,http://dx.doi.org/10.1371/journal.ppat.1004051,PMC3990711,24743583,CC BY,"Replication of plus-strand RNA viruses depends on recruited host factors that aid several critical steps during replication. Several of the co-opted host factors bind to the viral RNA, which plays multiple roles, including mRNA function, as an assembly platform for the viral replicase (VRC), template for RNA synthesis, and encapsidation during infection. It is likely that remodeling of the viral RNAs and RNA-protein complexes during the switch from one step to another requires RNA helicases. In this paper, we have discovered a second group of cellular RNA helicases, including the eIF4AIII-like yeast Fal1p and the DDX5-like Dbp3p and the orthologous plant AtRH2 and AtRH5 DEAD box helicases, which are co-opted by tombusviruses. Unlike the previously characterized DDX3-like AtRH20/Ded1p helicases that bind to the 3′ terminal promoter region in the viral minus-strand (−)RNA, the other class of eIF4AIII-like RNA helicases bind to a different cis-acting element, namely the 5′ proximal RIII(−) replication enhancer (REN) element in the TBSV (−)RNA. We show that the binding of AtRH2 and AtRH5 helicases to the TBSV (−)RNA could unwind the dsRNA structure within the RIII(−) REN. This unique characteristic allows the eIF4AIII-like helicases to perform novel pro-viral functions involving the RIII(−) REN in stimulation of plus-strand (+)RNA synthesis. We also show that AtRH2 and AtRH5 helicases are components of the tombusvirus VRCs based on co-purification experiments. We propose that eIF4AIII-like helicases destabilize dsRNA replication intermediate within the RIII(−) REN that promotes bringing the 5′ and 3′ terminal (−)RNA sequences in close vicinity via long-range RNA-RNA base pairing. This newly formed RNA structure promoted by eIF4AIII helicase together with AtRH20 helicase might facilitate the recycling of the viral replicases for multiple rounds of (+)-strand synthesis, thus resulting in asymmetrical viral replication.",2014 Apr 17,"['Kovalev, Nikolay', 'Nagy, Peter D.']",PLoS Pathog,,,False
a92044661e4999b7f34275c0bf742cf6e03955b5,PMC,Deficient IFN Signaling by Myeloid Cells Leads to MAVS-Dependent Virus-Induced Sepsis,http://dx.doi.org/10.1371/journal.ppat.1004086,PMC3990718,24743949,CC BY,"The type I interferon (IFN) signaling response limits infection of many RNA and DNA viruses. To define key cell types that require type I IFN signaling to orchestrate immunity against West Nile virus (WNV), we infected mice with conditional deletions of the type I IFN receptor (IFNAR) gene. Deletion of the Ifnar gene in subsets of myeloid cells resulted in uncontrolled WNV replication, vasoactive cytokine production, sepsis, organ damage, and death that were remarkably similar to infection of Ifnar (−/−) mice completely lacking type I IFN signaling. In Mavs(−/−)×Ifnar(−/−) myeloid cells and mice lacking both Ifnar and the RIG-I-like receptor adaptor gene Mavs, cytokine production was muted despite high levels of WNV infection. Thus, in myeloid cells, viral infection triggers signaling through MAVS to induce proinflammatory cytokines that can result in sepsis and organ damage. Viral pathogenesis was caused in part by massive complement activation, as liver damage was minimized in animals lacking complement components C3 or factor B or treated with neutralizing anti-C5 antibodies. Disease in Ifnar (−/−) and CD11c Cre(+) Ifnar (f/f) mice also was facilitated by the proinflammatory cytokine TNF-α, as blocking antibodies diminished complement activation and prolonged survival without altering viral burden. Collectively, our findings establish the dominant role of type I IFN signaling in myeloid cells in restricting virus infection and controlling pathological inflammation and tissue injury.",2014 Apr 17,"['Pinto, Amelia K.', 'Ramos, Hilario J.', 'Wu, Xiaobo', 'Aggarwal, Shilpa', 'Shrestha, Bimmi', 'Gorman, Matthew', 'Kim, Kristin Y.', 'Suthar, Mehul S.', 'Atkinson, John P.', 'Gale Jr, Michael', 'Diamond, Michael S.']",PLoS Pathog,,,True
ad4fdcc457c573beda847d0999a02d9e1c9fb151,PMC,Deficient IFN Signaling by Myeloid Cells Leads to MAVS-Dependent Virus-Induced Sepsis,http://dx.doi.org/10.1371/journal.ppat.1004086,PMC3990718,24743949,CC BY,"The type I interferon (IFN) signaling response limits infection of many RNA and DNA viruses. To define key cell types that require type I IFN signaling to orchestrate immunity against West Nile virus (WNV), we infected mice with conditional deletions of the type I IFN receptor (IFNAR) gene. Deletion of the Ifnar gene in subsets of myeloid cells resulted in uncontrolled WNV replication, vasoactive cytokine production, sepsis, organ damage, and death that were remarkably similar to infection of Ifnar (−/−) mice completely lacking type I IFN signaling. In Mavs(−/−)×Ifnar(−/−) myeloid cells and mice lacking both Ifnar and the RIG-I-like receptor adaptor gene Mavs, cytokine production was muted despite high levels of WNV infection. Thus, in myeloid cells, viral infection triggers signaling through MAVS to induce proinflammatory cytokines that can result in sepsis and organ damage. Viral pathogenesis was caused in part by massive complement activation, as liver damage was minimized in animals lacking complement components C3 or factor B or treated with neutralizing anti-C5 antibodies. Disease in Ifnar (−/−) and CD11c Cre(+) Ifnar (f/f) mice also was facilitated by the proinflammatory cytokine TNF-α, as blocking antibodies diminished complement activation and prolonged survival without altering viral burden. Collectively, our findings establish the dominant role of type I IFN signaling in myeloid cells in restricting virus infection and controlling pathological inflammation and tissue injury.",2014 Apr 17,"['Pinto, Amelia K.', 'Ramos, Hilario J.', 'Wu, Xiaobo', 'Aggarwal, Shilpa', 'Shrestha, Bimmi', 'Gorman, Matthew', 'Kim, Kristin Y.', 'Suthar, Mehul S.', 'Atkinson, John P.', 'Gale Jr, Michael', 'Diamond, Michael S.']",PLoS Pathog,,,False
0c361ff7d4302f316571dd1b313c4b841c15c66a,PMC,Deficient IFN Signaling by Myeloid Cells Leads to MAVS-Dependent Virus-Induced Sepsis,http://dx.doi.org/10.1371/journal.ppat.1004086,PMC3990718,24743949,CC BY,"The type I interferon (IFN) signaling response limits infection of many RNA and DNA viruses. To define key cell types that require type I IFN signaling to orchestrate immunity against West Nile virus (WNV), we infected mice with conditional deletions of the type I IFN receptor (IFNAR) gene. Deletion of the Ifnar gene in subsets of myeloid cells resulted in uncontrolled WNV replication, vasoactive cytokine production, sepsis, organ damage, and death that were remarkably similar to infection of Ifnar (−/−) mice completely lacking type I IFN signaling. In Mavs(−/−)×Ifnar(−/−) myeloid cells and mice lacking both Ifnar and the RIG-I-like receptor adaptor gene Mavs, cytokine production was muted despite high levels of WNV infection. Thus, in myeloid cells, viral infection triggers signaling through MAVS to induce proinflammatory cytokines that can result in sepsis and organ damage. Viral pathogenesis was caused in part by massive complement activation, as liver damage was minimized in animals lacking complement components C3 or factor B or treated with neutralizing anti-C5 antibodies. Disease in Ifnar (−/−) and CD11c Cre(+) Ifnar (f/f) mice also was facilitated by the proinflammatory cytokine TNF-α, as blocking antibodies diminished complement activation and prolonged survival without altering viral burden. Collectively, our findings establish the dominant role of type I IFN signaling in myeloid cells in restricting virus infection and controlling pathological inflammation and tissue injury.",2014 Apr 17,"['Pinto, Amelia K.', 'Ramos, Hilario J.', 'Wu, Xiaobo', 'Aggarwal, Shilpa', 'Shrestha, Bimmi', 'Gorman, Matthew', 'Kim, Kristin Y.', 'Suthar, Mehul S.', 'Atkinson, John P.', 'Gale Jr, Michael', 'Diamond, Michael S.']",PLoS Pathog,,,False
a69e74d1f10d384fc703f38564490fe994bc7bf2,PMC,Deficient IFN Signaling by Myeloid Cells Leads to MAVS-Dependent Virus-Induced Sepsis,http://dx.doi.org/10.1371/journal.ppat.1004086,PMC3990718,24743949,CC BY,"The type I interferon (IFN) signaling response limits infection of many RNA and DNA viruses. To define key cell types that require type I IFN signaling to orchestrate immunity against West Nile virus (WNV), we infected mice with conditional deletions of the type I IFN receptor (IFNAR) gene. Deletion of the Ifnar gene in subsets of myeloid cells resulted in uncontrolled WNV replication, vasoactive cytokine production, sepsis, organ damage, and death that were remarkably similar to infection of Ifnar (−/−) mice completely lacking type I IFN signaling. In Mavs(−/−)×Ifnar(−/−) myeloid cells and mice lacking both Ifnar and the RIG-I-like receptor adaptor gene Mavs, cytokine production was muted despite high levels of WNV infection. Thus, in myeloid cells, viral infection triggers signaling through MAVS to induce proinflammatory cytokines that can result in sepsis and organ damage. Viral pathogenesis was caused in part by massive complement activation, as liver damage was minimized in animals lacking complement components C3 or factor B or treated with neutralizing anti-C5 antibodies. Disease in Ifnar (−/−) and CD11c Cre(+) Ifnar (f/f) mice also was facilitated by the proinflammatory cytokine TNF-α, as blocking antibodies diminished complement activation and prolonged survival without altering viral burden. Collectively, our findings establish the dominant role of type I IFN signaling in myeloid cells in restricting virus infection and controlling pathological inflammation and tissue injury.",2014 Apr 17,"['Pinto, Amelia K.', 'Ramos, Hilario J.', 'Wu, Xiaobo', 'Aggarwal, Shilpa', 'Shrestha, Bimmi', 'Gorman, Matthew', 'Kim, Kristin Y.', 'Suthar, Mehul S.', 'Atkinson, John P.', 'Gale Jr, Michael', 'Diamond, Michael S.']",PLoS Pathog,,,False
423a10412afb0aef150b143711b96b0dae789ba4,PMC,Deficient IFN Signaling by Myeloid Cells Leads to MAVS-Dependent Virus-Induced Sepsis,http://dx.doi.org/10.1371/journal.ppat.1004086,PMC3990718,24743949,CC BY,"The type I interferon (IFN) signaling response limits infection of many RNA and DNA viruses. To define key cell types that require type I IFN signaling to orchestrate immunity against West Nile virus (WNV), we infected mice with conditional deletions of the type I IFN receptor (IFNAR) gene. Deletion of the Ifnar gene in subsets of myeloid cells resulted in uncontrolled WNV replication, vasoactive cytokine production, sepsis, organ damage, and death that were remarkably similar to infection of Ifnar (−/−) mice completely lacking type I IFN signaling. In Mavs(−/−)×Ifnar(−/−) myeloid cells and mice lacking both Ifnar and the RIG-I-like receptor adaptor gene Mavs, cytokine production was muted despite high levels of WNV infection. Thus, in myeloid cells, viral infection triggers signaling through MAVS to induce proinflammatory cytokines that can result in sepsis and organ damage. Viral pathogenesis was caused in part by massive complement activation, as liver damage was minimized in animals lacking complement components C3 or factor B or treated with neutralizing anti-C5 antibodies. Disease in Ifnar (−/−) and CD11c Cre(+) Ifnar (f/f) mice also was facilitated by the proinflammatory cytokine TNF-α, as blocking antibodies diminished complement activation and prolonged survival without altering viral burden. Collectively, our findings establish the dominant role of type I IFN signaling in myeloid cells in restricting virus infection and controlling pathological inflammation and tissue injury.",2014 Apr 17,"['Pinto, Amelia K.', 'Ramos, Hilario J.', 'Wu, Xiaobo', 'Aggarwal, Shilpa', 'Shrestha, Bimmi', 'Gorman, Matthew', 'Kim, Kristin Y.', 'Suthar, Mehul S.', 'Atkinson, John P.', 'Gale Jr, Michael', 'Diamond, Michael S.']",PLoS Pathog,,,False
5e022a5ce7ca2c5463c52d20ed1a1e63259c17a7,PMC,Complete Genome Sequence of Porcine Coronavirus HKU15 Strain IN2847 from the United States,http://dx.doi.org/10.1128/genomeA.00291-14,PMC3990748,24744332,CC BY,"Porcine coronavirus HKU15 (PorCoV HKU15) was first detected in pigs with clinical diseases in February 2014 in the United States. Here, we report the complete genome sequence of Indiana strain IN2847, which might be useful for understanding the molecular profile of PorCoV HKU15.",2014 Apr 17,"['Wang, Leyi', 'Zhang, Yan', 'Byrum, Beverly']",Genome Announc,,,True
3207d738e32216ee810dcb38fdbdf73d47eafaca,PMC,Glycyrrhizin improves p75NTR-associated sciatic nerve regeneration in a BALB/c mouse model,http://dx.doi.org/10.3892/etm.2014.1546,PMC3991491,24940400,CC BY,"Glycyrrhizin has a role in immune regulation in the central nervous system, but its impact on sciatic nerve injury had not previously been reported. In this study, a BALB/c mouse model of sciatic nerve injury was used to explore the role of glycyrrhizin in sciatic nerve repair and its underlying mechanism. Glycyrrhizin with intragastric gavage of 10 and 20 mg/kg weight per day (mid- and high-dose, respectively) inhibited p75 neurotrophin receptor (p75NTR) expression at the protein and mRNA levels versus the 5 mg/kg (low-dose) group and control (0.9% NaCl solution) at one, two, four and eight weeks following sciatic nerve injury, and simultaneously improved the action potential amplitude and motor nerve conductive velocity. Combined Marsland, Glees and Erikson’s silver stain and Luxol fast blue staining results indicated that high- and mid-dose glycyrrhizin promoted improved sciatic nerve myelination compared with the low-dose or control groups eight weeks after injury. Immunofluorescence staining demonstrated that glycyrrhizin had an inhibitory effect to a certain degree on local hypertrophic scar and inflammatory responses in the mouse model. In conclusion, glycyrrhizin can promote sciatic nerve regeneration and functional repair, in which doses of 10 and 20 mg/kg per day are more effective than lower doses, and such regeneration is associated with the downregulation of p75NTR.",2014 May 14,"['JIA, YU-XI', 'LI, JIN-RAN', 'MAO, CUI-YING', 'YIN, WEI-TIAN', 'JIANG, RI-HUA']",Exp Ther Med,,,True
aca7762f80af606fe3c6d2614096db74f1398368,PMC,Development of VHH Antibodies against Dengue Virus Type 2 NS1 and Comparison with Monoclonal Antibodies for Use in Immunological Diagnosis,http://dx.doi.org/10.1371/journal.pone.0095263,PMC3994031,24751715,CC BY,"The possibility of using variable domain heavy-chain antibodies (VHH antibodies) as diagnostic tools for dengue virus (DENV) type 2 NS1 protein was investigated and compared with the use of conventional monoclonal antibodies. After successful expression of DENV type 2 NS1 protein, the genes of VHH antibodies against NS1 protein were biopanned from a non-immune llama library by phage display. VHH antibodies were then expressed and purified from Escherichia coli. Simultaneously, monoclonal antibodies were obtained by the conventional route. Sequence analysis of the VHH antibodies revealed novel and long complementarity determining regions 3 (CDR3). Epitope mapping was performed via a phage display peptide library using purified VHH and monoclonal antibodies as targets. Interestingly, the same region of NS1, which comprises amino acids (224)HWPKPHTLW(232), was conserved for both kinds of antibodies displaying the consensus motif histidine-tryptophan-tryptophan or tryptophan-proline-tryptophan. The two types of antibodies were used to prepare rapid diagnostic kits based on immunochromatographic assay. The VHH antibody immobilized rapid diagnostic kit showed better sensitivity and specificity than the monoclonal antibody immobilized rapid diagnostic kit, which might be due to the long CDR3 regions of the VHH antibodies and their ability to bind to the pocket and cleft of the targeted antigen. This demonstrates that VHH antibodies are likely to be an option for developing point-of-care tests against DENV infection.",2014 Apr 21,"['Fatima, Aneela', 'Wang, Haiying', 'Kang, Keren', 'Xia, Liliang', 'Wang, Ying', 'Ye, Wei', 'Wang, Jufang', 'Wang, Xiaoning']",PLoS One,,,True
98bc863e44dea730a7952a8b6bc62292fe5da07a,PMC,Viral Infection Is Not Uncommon in Adult Patients with Severe Hospital-Acquired Pneumonia,http://dx.doi.org/10.1371/journal.pone.0095865,PMC3994115,24752070,CC BY,"BACKGROUND: Viral pathogens have not generally been regarded as important causes of severe hospital-acquired pneumonia (HAP), except in patients with hematologic malignancy or transplant recipients. We investigated the role and distribution of viruses in adult with severe HAP who required intensive care. METHODS: From March 2010 to February 2012, adult patients with severe HAP required admission to the intensive care unit (ICU), 28-bed medical ICU in a tertiary care hospital, were prospectively enrolled. Respiratory viruses were detected using multiplex reverse-transcription polymerase chain reaction and/or shell vial culture. RESULTS: A total of 262 patients were enrolled and 107 patients (40.8%) underwent bronchoscopic BAL for etiologic diagnosis. One hundred and fifty-six patients (59.5%) had bacterial infections and 59 patients (22.5%) had viral infections. Viruses were detected in BAL fluid specimens of 37 patients (62.7%, 37/59). The most commonly identified viruses were respiratory syncytial virus and parainfluenza virus (both 27.1%, 16/59), followed by rhinovirus (25.4%, 15/59), and influenza virus (16.9%, 10/59). Twenty-one patients (8.0%, 21/262) had bacterial-viral coinfections and Staphylococcus aureus was the most commonly coexisting bacteria (n = 10). Viral infection in non-immunocompromised patients was not uncommon (11.1%, 16/143), although it was not as frequent as that in immunocompromised patients (36.4%, 43/119). Non-immunocompromised patients were significantly older than immunocompromised patients and had significantly higher rates of underlying chronic obstructive pulmonary disease, tuberculous destroyed lung and chronic kidney disease. The 28 day mortalities of patients with bacterial infections, viral infections and bacterial-viral coinfections were not significantly different (29.5%, 35.6% and 19.0%, respectively; p = 0.321). CONCLUSIONS: Viral pathogens are not uncommon in adult patients with severe HAP who required ICU admission. Since viral pathogens may cause severe HAP and could be a potential source of viral transmission, further investigation is required to delineate the role of viral pathogens in severe HAP.",2014 Apr 21,"['Hong, Hyo-Lim', 'Hong, Sang-Bum', 'Ko, Gwang-Beom', 'Huh, Jin Won', 'Sung, Heungsup', 'Do, Kyung-Hyun', 'Kim, Sung-Han', 'Lee, Sang-Oh', 'Kim, Mi-Na', 'Jeong, Jin-Yong', 'Lim, Chae-Man', 'Kim, Yang Soo', 'Woo, Jun Hee', 'Koh, Younsuck', 'Choi, Sang-Ho']",PLoS One,,,True
66f31952c8b998f8c9de4d34c17a7c2e0d2e35fa,PMC,Activation of the PKR/eIF2α signaling cascade inhibits replication of Newcastle disease virus,http://dx.doi.org/10.1186/1743-422X-11-62,PMC3994276,24684861,CC BY,"BACKGROUND: Newcastle Disease virus (NDV) causes severe and economically significant disease in almost all birds. However, factors that affect NDV replication in host cells are poorly understood. NDV generates long double-stranded RNA (dsRNA) molecules during transcription of single-stranded genomic RNA. Protein kinase R (PKR) is activated by dsRNA. The aim of this study was to elucidate the role of PKR in NDV infection. RESULTS: NDV infection led to the activation of dsRNA-dependent PKR and phosphorylation of its substrate, translation initiation factor eIF2α, in a dose-dependent manner by either the lentogenic strain LaSota or a velogenic strain Herts/33. PKR activation coincided with the accumulation of dsRNA induced by NDV infection. PKR knockdown remarkably decreased eIF2α phosphorylation as well as IFN-β mRNA levels, leading to the augmentation of extracellular virus titer. Furthermore, siRNA knockdown or phosphorylation of eIF2α or okadaic acid treatment significantly impaired NDV replication, indicating the critical role of the PKR/eIF2α signaling cascade in NDV infection. CONCLUSION: PKR is activated by dsRNA generated by NDV infection and inhibits NDV replication by eIF2α phosphorylation. This study provides insight into NDV-host interactions for the development of candidate antiviral strategies.",2014 Mar 31,"['Zhang, Shilei', 'Sun, Yingjie', 'Chen, Hongjun', 'Dai, Yabin', 'Zhan, Yuan', 'Yu, Shengqing', 'Qiu, Xusheng', 'Tan, Lei', 'Song, Cuiping', 'Ding, Chan']",Virol J,,,True
417a6772d67e3b958d27a80ed09cabfea228d432,PMC,Impact of 2013 south Asian haze crisis: study of physical and psychological symptoms and perceived dangerousness of pollution level,http://dx.doi.org/10.1186/1471-244X-14-81,PMC3995317,24642046,CC BY,"BACKGROUND: The widespread forest fires in Indonesia in June 2013 led to widespread haze to neighbouring countries. This is the first study in the medical literature reporting the acute physical and psychological symptoms of the general population during a haze crisis. We evaluated the factors that are associated with psychological stress of haze exposure. METHODS: This study was conducted between June 21 to June 26, 2013. Participants were recruited by an online recruitment post and snowball sampling techniques. Participants were required to complete an online survey which was composed of demographics questionnaire, physical symptom checklist, perceived dangerous Pollutant Standard Index (PSI) value and views on the N-95 mask and the Impact of Event Scale-Revised (IES-R). RESULTS: A total of 298 participants returned the completed study questionnaire. The respondents reported a mean number of 4.03 physical symptoms (S.D. = 2.6). The five most common physical symptoms include mouth or throat discomfort (68.8%), nose discomfort (64.1%), eye discomfort (60.7%), headache (50.3%) and breathing difficulty (40.3%). The total IES-R score was 18.47 (S.D. = 11.69) which indicated that the study population experienced mild psychological stress but not to the extent of acute stress reaction syndrome. The perceived dangerous PSI level and number of physical symptoms were significantly associated with the mean intrusion score, mean hyper-arousal score, total mean IES-R score and total IES-R score (p < 0.05). CONCLUSIONS: Our findings suggest that a haze crisis is associated with acute physical symptoms and mild psychological stress. The number of physical symptoms and the perceived dangerous PSI values are important factors associated with psychological stress.",2014 Mar 19,"['Ho, Roger C', 'Zhang, Melvyn W', 'Ho, Cyrus S', 'Pan, Fang', 'Lu, Yanxia', 'Sharma, Vijay K']",BMC Psychiatry,,,True
a11b3479a9f0e004870ecefa643c4c311c6066cb,PMC,Fluorescence in situ hybridization investigation of potentially pathogenic bacteria involved in neonatal porcine diarrhea,http://dx.doi.org/10.1186/1746-6148-10-68,PMC3995547,24628856,CC BY,"BACKGROUND: Neonatal diarrhea is a multifactorial condition commonly present on pig farms and leads to economic losses due to increased morbidity and mortality of piglets. Immature immune system and lack of fully established microbiota at birth predispose neonatal piglets to infection with enteric pathogens. The microorganisms that for decades have been associated with enteritis and diarrhea in suckling piglets are: rotavirus A, coronavirus, enterotoxigenic Escherichia coli (ETEC), Clostridium perfringens type C, Cryptosporidium spp., Giardia spp., Cystoisospora suis and Strongyloides ransomi. However, in recent years, the pig industry has experienced an increased number of neonatal diarrhea cases in which the above mentioned pathogens are no longer detected. Potentially pathogenic bacteria have recently received focus in the research on the possible etiology of neonatal diarrhea not caused by common pathogens. The primary aim of this study was to investigate the role of E. coli, Enterococcus spp., C. perfringens and C. difficile in the pathogenesis of neonatal porcine diarrhea with no established casual agents. Fluorescence in situ hybridization with oligonucleotide probes was applied on the fixed intestinal tissue samples from 51 diarrheic and 50 non-diarrheic piglets collected from four Danish farms during outbreaks of neonatal diarrhea not caused by well-known enteric pathogens. Furthermore, an association between the presence of these bacteria and histological lesions was evaluated. RESULTS: The prevalence of fluorescence signals specific for E. coli, C. perfringens and C. difficile was similar in both groups of piglets. However, Enterococcus spp. was primarily detected in the diarrheic piglets. Furthermore, adherent bacteria were detected in 37 % diarrheic and 14 % non-diarrheic piglets. These bacteria were identified as E. coli and Enterococcus spp. and their presence in the intestinal mucosa was associated with histopathological changes. CONCLUSIONS: The results of this study showed that simultaneous colonization of the intestinal mucosa by adherent non-ETEC E. coli and Enterococcus spp. can be involved in the pathogenesis of neonatal porcine diarrhea. These bacteria should be considered in diagnosis of diarrhea in piglets, when detection of common, well-known enteric agents is unsuccessful.",2014 Mar 14,"['Jonach, Beata', 'Boye, Mette', 'Stockmarr, Anders', 'Jensen, Tim Kåre']",BMC Vet Res,,,True
93edcf98f17f9827882fbaed728fb18a8a51cc1d,PMC,Serological report of pandemic (H1N1) 2009 infection among cats in Northeastern China in 2012-02 and 2013-03,http://dx.doi.org/10.1186/1743-422X-11-49,PMC3995557,24624924,CC BY,"BACKGROUND: Influenza A virus has a wide range of hosts. It has not only infected human, but also been reported interspecies transmission from humans to other animals, such as pigs, poultry, dogs and cats. However, prevalence of A (H1N1) pdm09 influenza virus infections in cats in northeastern China is unknown. Therefore, the prevalence of A (H1N1) pdm09 influenza virus infections was performed among cats in northeastern China in this study. FINDINGS: Of all samples in this study, the overall seroprevalence of pandemic (H1N1) 2009 infection in cats was 21% (240/1140). It also showed a higher prevalence rate of pandemic(H1N1) 2009 infection in pet cats (30.6%) than roaming cats (11%) based on NT. In addition, the results also showed a trend of difference in term of species of cats and it was statistically significant. CONCLUSIONS: This is the first survey on the seroprevalence of pandemic (H1N1) 2009 infection among cats in northeastern China. This study has observed a relatively high seroprevalence of pandemic (H1N1) 2009 among different cat populations in northeastern China, similar seroprevalence studies should be conducted elsewhere.",2014 Mar 14,"['Zhao, Fu-Rong', 'Liu, Chun-Guo', 'Yin, Xin', 'Zhou, Dong-Hui', 'Wei, Ping', 'Chang, Hui-Yun']",Virol J,,,True
018b618ea132d47ffb43b003a6c78cb9eeadc017,PMC,Unique Epitopes Recognized by Antibodies Induced in Chikungunya Virus-Infected Non-Human Primates: Implications for the Study of Immunopathology and Vaccine Development,http://dx.doi.org/10.1371/journal.pone.0095647,PMC3995782,24755730,CC BY,"Chikungunya virus (CHIKV) is an Alphavirus that causes chronic and incapacitating arthralgia in humans. Although patient cohort studies have shown the production of CHIKV specific antibodies, the fine specificity of the antibody response against CHIKV is not completely defined. The macaque model of CHIKV infection was established due to limitations of clinical specimens. More importantly, its close relation to humans will allow the study of chronic infection and further identify important CHIKV targets. In this study, serum samples from CHIKV-infected macaques collected at different time-points post infection were used to characterize the antibody production pattern and kinetics. Results revealed that anti-CHIKV antibodies were neutralizing and the E2 glycoprotein, Capsid, nsP1, nsP3 and nsP4 proteins were targets of the anti-CHIKV antibody response in macaques. Furthermore, linear B-cell epitopes recognized by these anti-CHIKV antibodies were identified, and mapped to their structural localization. This characterizes the specificity of anti-CHIKV antibody response in macaques and further demonstrates the importance of the different regions in CHIKV-encoded proteins in the adaptive immune response. Information from this study provides critical knowledge that will aid in the understanding of CHIKV infection and immunity, vaccine design, and pre-clinical efficacy studies.",2014 Apr 22,"['Kam, Yiu-Wing', 'Lee, Wendy W. L.', 'Simarmata, Diane', 'Le Grand, Roger', 'Tolou, Hugues', 'Merits, Andres', 'Roques, Pierre', 'Ng, Lisa F. P.']",PLoS One,,,True
08e013666eb4c5dde725c49c2f2b701f05572a0c,PMC,Unique Epitopes Recognized by Antibodies Induced in Chikungunya Virus-Infected Non-Human Primates: Implications for the Study of Immunopathology and Vaccine Development,http://dx.doi.org/10.1371/journal.pone.0095647,PMC3995782,24755730,CC BY,"Chikungunya virus (CHIKV) is an Alphavirus that causes chronic and incapacitating arthralgia in humans. Although patient cohort studies have shown the production of CHIKV specific antibodies, the fine specificity of the antibody response against CHIKV is not completely defined. The macaque model of CHIKV infection was established due to limitations of clinical specimens. More importantly, its close relation to humans will allow the study of chronic infection and further identify important CHIKV targets. In this study, serum samples from CHIKV-infected macaques collected at different time-points post infection were used to characterize the antibody production pattern and kinetics. Results revealed that anti-CHIKV antibodies were neutralizing and the E2 glycoprotein, Capsid, nsP1, nsP3 and nsP4 proteins were targets of the anti-CHIKV antibody response in macaques. Furthermore, linear B-cell epitopes recognized by these anti-CHIKV antibodies were identified, and mapped to their structural localization. This characterizes the specificity of anti-CHIKV antibody response in macaques and further demonstrates the importance of the different regions in CHIKV-encoded proteins in the adaptive immune response. Information from this study provides critical knowledge that will aid in the understanding of CHIKV infection and immunity, vaccine design, and pre-clinical efficacy studies.",2014 Apr 22,"['Kam, Yiu-Wing', 'Lee, Wendy W. L.', 'Simarmata, Diane', 'Le Grand, Roger', 'Tolou, Hugues', 'Merits, Andres', 'Roques, Pierre', 'Ng, Lisa F. P.']",PLoS One,,,False
491f229f1a4bc9fb8f4c85097040666e5ad1c455,PMC,Determining the dynamics of influenza transmission by age,http://dx.doi.org/10.1186/1742-7622-11-4,PMC3997935,24656239,CC BY,"BACKGROUND: It is widely accepted that influenza transmission dynamics vary by age; however methods to quantify the reproductive number by age group are limited. We introduce a simple method to estimate the reproductive number by modifying the method originally proposed by Wallinga and Teunis and using existing information on contact patterns between age groups. We additionally perform a sensitivity analysis to determine the potential impact of differential healthcare seeking patterns by age. We illustrate this method using data from the 2009 H1N1 Influenza pandemic in Gauteng Province, South Africa. RESULTS: Our results are consistent with others in showing decreased transmission with age. We show that results can change markedly when we make the account for differential healthcare seeking behaviors by age. CONCLUSIONS: We show substantial heterogeneity in transmission by age group during the Influenza A H1N1 pandemic in South Africa. This information can greatly assist in targeting interventions and implementing social distancing measures.",2014 Mar 21,"['White, Laura F', 'Archer, Brett', 'Pagano, Marcello']",Emerg Themes Epidemiol,,,True
90394841ad2cbaec78bf51646d5ca1ae26fadba6,PMC,Bayesian Analysis for Inference of an Emerging Epidemic: Citrus Canker in Urban Landscapes,http://dx.doi.org/10.1371/journal.pcbi.1003587,PMC3998883,24762851,CC0,"Outbreaks of infectious diseases require a rapid response from policy makers. The choice of an adequate level of response relies upon available knowledge of the spatial and temporal parameters governing pathogen spread, affecting, amongst others, the predicted severity of the epidemic. Yet, when a new pathogen is introduced into an alien environment, such information is often lacking or of no use, and epidemiological parameters must be estimated from the first observations of the epidemic. This poses a challenge to epidemiologists: how quickly can the parameters of an emerging disease be estimated? How soon can the future progress of the epidemic be reliably predicted? We investigate these issues using a unique, spatially and temporally resolved dataset for the invasion of a plant disease, Asiatic citrus canker in urban Miami. We use epidemiological models, Bayesian Markov-chain Monte Carlo, and advanced spatial statistical methods to analyse rates and extent of spread of the disease. A rich and complex epidemic behaviour is revealed. The spatial scale of spread is approximately constant over time and can be estimated rapidly with great precision (although the evidence for long-range transmission is inconclusive). In contrast, the rate of infection is characterised by strong monthly fluctuations that we associate with extreme weather events. Uninformed predictions from the early stages of the epidemic, assuming complete ignorance of the future environmental drivers, fail because of the unpredictable variability of the infection rate. Conversely, predictions improve dramatically if we assume prior knowledge of either the main environmental trend, or the main environmental events. A contrast emerges between the high detail attained by modelling in the spatiotemporal description of the epidemic and the bottleneck imposed on epidemic prediction by the limits of meteorological predictability. We argue that identifying such bottlenecks will be a fundamental step in future modelling of weather-driven epidemics.",2014 Apr 24,"['Neri, Franco M.', 'Cook, Alex R.', 'Gibson, Gavin J.', 'Gottwald, Tim R.', 'Gilligan, Christopher A.']",PLoS Comput Biol,,,True
d7454f33ce536b8ede6b9540b21f09c407a5e708,PMC,Bayesian Analysis for Inference of an Emerging Epidemic: Citrus Canker in Urban Landscapes,http://dx.doi.org/10.1371/journal.pcbi.1003587,PMC3998883,24762851,CC0,"Outbreaks of infectious diseases require a rapid response from policy makers. The choice of an adequate level of response relies upon available knowledge of the spatial and temporal parameters governing pathogen spread, affecting, amongst others, the predicted severity of the epidemic. Yet, when a new pathogen is introduced into an alien environment, such information is often lacking or of no use, and epidemiological parameters must be estimated from the first observations of the epidemic. This poses a challenge to epidemiologists: how quickly can the parameters of an emerging disease be estimated? How soon can the future progress of the epidemic be reliably predicted? We investigate these issues using a unique, spatially and temporally resolved dataset for the invasion of a plant disease, Asiatic citrus canker in urban Miami. We use epidemiological models, Bayesian Markov-chain Monte Carlo, and advanced spatial statistical methods to analyse rates and extent of spread of the disease. A rich and complex epidemic behaviour is revealed. The spatial scale of spread is approximately constant over time and can be estimated rapidly with great precision (although the evidence for long-range transmission is inconclusive). In contrast, the rate of infection is characterised by strong monthly fluctuations that we associate with extreme weather events. Uninformed predictions from the early stages of the epidemic, assuming complete ignorance of the future environmental drivers, fail because of the unpredictable variability of the infection rate. Conversely, predictions improve dramatically if we assume prior knowledge of either the main environmental trend, or the main environmental events. A contrast emerges between the high detail attained by modelling in the spatiotemporal description of the epidemic and the bottleneck imposed on epidemic prediction by the limits of meteorological predictability. We argue that identifying such bottlenecks will be a fundamental step in future modelling of weather-driven epidemics.",2014 Apr 24,"['Neri, Franco M.', 'Cook, Alex R.', 'Gibson, Gavin J.', 'Gottwald, Tim R.', 'Gilligan, Christopher A.']",PLoS Comput Biol,,,False
03e779f9defa0b9cb6a9943947e41b9c1532e3d3,PMC,Bayesian Analysis for Inference of an Emerging Epidemic: Citrus Canker in Urban Landscapes,http://dx.doi.org/10.1371/journal.pcbi.1003587,PMC3998883,24762851,CC0,"Outbreaks of infectious diseases require a rapid response from policy makers. The choice of an adequate level of response relies upon available knowledge of the spatial and temporal parameters governing pathogen spread, affecting, amongst others, the predicted severity of the epidemic. Yet, when a new pathogen is introduced into an alien environment, such information is often lacking or of no use, and epidemiological parameters must be estimated from the first observations of the epidemic. This poses a challenge to epidemiologists: how quickly can the parameters of an emerging disease be estimated? How soon can the future progress of the epidemic be reliably predicted? We investigate these issues using a unique, spatially and temporally resolved dataset for the invasion of a plant disease, Asiatic citrus canker in urban Miami. We use epidemiological models, Bayesian Markov-chain Monte Carlo, and advanced spatial statistical methods to analyse rates and extent of spread of the disease. A rich and complex epidemic behaviour is revealed. The spatial scale of spread is approximately constant over time and can be estimated rapidly with great precision (although the evidence for long-range transmission is inconclusive). In contrast, the rate of infection is characterised by strong monthly fluctuations that we associate with extreme weather events. Uninformed predictions from the early stages of the epidemic, assuming complete ignorance of the future environmental drivers, fail because of the unpredictable variability of the infection rate. Conversely, predictions improve dramatically if we assume prior knowledge of either the main environmental trend, or the main environmental events. A contrast emerges between the high detail attained by modelling in the spatiotemporal description of the epidemic and the bottleneck imposed on epidemic prediction by the limits of meteorological predictability. We argue that identifying such bottlenecks will be a fundamental step in future modelling of weather-driven epidemics.",2014 Apr 24,"['Neri, Franco M.', 'Cook, Alex R.', 'Gibson, Gavin J.', 'Gottwald, Tim R.', 'Gilligan, Christopher A.']",PLoS Comput Biol,,,True
e2b354fb613a71ab7f449318fe0d8c20d535e9b1,PMC,The effect of New Neonatal Porcine Diarrhoea Syndrome (NNPDS) on average daily gain and mortality in 4 Danish pig herds,http://dx.doi.org/10.1186/1746-6148-10-90,PMC3999350,24755093,CC BY,"BACKGROUND: The study evaluated the effect of New Neonatal Porcine Diarrhoea Syndrome (NNPDS) on average daily gain (ADG) and mortality and described the clinical manifestations in four herds suffering from the syndrome. NNPDS is a diarrhoeic syndrome affecting piglets within the first week of life, which is not caused by enterotoxigenic Escherichia coli (ETEC), Clostridium perfringens (C. perfringens) type A/C, Clostridium difficile (C. difficile), rotavirus A, coronavirus, Cystoisospora suis, Strongyloides ransomi, Giardia spp or Cryptosporidium spp. RESULTS: Piglets were estimated to have a negative ADG of 9 and 14 g when diarrhoeic for 1 day and >1 day respectively. However, if only diarrhoeic on the day of birth, no negative effect on ADG was seen. Piglets originating from severely affected litters were estimated to have a reduced ADG of 38 g. The study did not show an overall effect of diarrhoea on mortality, but herd of origin, sow parity, birth weight, and gender were significantly associated with mortality. In one of the herds, approximately 25% of the diarrhoeic piglets vs. 6% of the non-diarrhoeic piglets died, and 74% of necropsied piglets were diagnosed with enteritis. These findings indicate that the high mortality seen in this herd was due to diarrhoea. CONCLUSIONS: NNPDS negatively affected ADG in piglets, and even piglets that were diarrhoeic for one day only experienced a reduction in ADG. However, the study showed that diarrhoea restricted to the day of birth did not affect ADG and suggested this phenomenon to be unrelated to the syndrome. Since the diarrhoeal status of the litter had important effects on ADG, future research on NNPDS probably ought to focus on piglets from severely affected litters. The study showed important dissimilarities in the course of diarrhoea between the herds, and one herd was considerably more affected than the others. Within this herd, NNPDS seemed to be associated with a higher mortality, whereas in general the study did not show lethal effects of NNPDS.",2014 Apr 22,"['Kongsted, Hanne', 'Stege, Helle', 'Toft, Nils', 'Nielsen, Jens P']",BMC Vet Res,,,True
e608f2a6b99e0e74c16aa9085128690e20b59ea0,PMC,Severe acute respiratory syndrome-coronavirus infection in aged nonhuman primates is associated with modulated pulmonary and systemic immune responses,http://dx.doi.org/10.1186/1742-4933-11-4,PMC3999990,24642138,CC BY,"BACKGROUND: Many respiratory viruses disproportionately impact the elderly. Likewise, advanced age correlated with more adverse disease outcomes following severe acute respiratory syndrome coronavirus (SARS-CoV) infection in humans. We used an aged African green monkey SARS-CoV infection model to better understand age-related mechanisms of increased susceptibility to viral respiratory infections. Nonhuman primates are critical translational models for such research given their similarities to humans in immune-ageing as well as lung structure. RESULTS: Significant age- and infection-dependent differences were observed in both systemic and mucosal immune compartments. Peripheral lymphocytes, specifically CD8 T and B cells were significantly lower in aged monkeys pre- and post- SARS-CoV infection, while neutrophil and monocyte numbers were not impacted by age or infection status. Serum proinflammatory cytokines were similar in both age groups, whereas significantly lower levels of IL-1beta, IL-18, IL-6, IL-12 and IL-15 were detected in the lungs of SARS-CoV-infected aged monkeys at either 5 or 10 days post infection. Total lung leukocyte numbers and relative frequency of CD8 T cells, B cells, macrophages and dendritic cells were greatly reduced in the aged host during SARS-CoV infection, despite high levels of chemoattractants for many of these cells in the aged lung. Dendritic cells and monocytes/macrophages showed age-dependent differences in activation and chemokine receptor profiles, while the CD8 T cell and B cell responses were significantly reduced in the aged host. In examination of viral titers, significantly higher levels of SARS-CoV were detected in the nasal swabs early, at day 1 post infection, in aged as compared to juvenile monkeys, but virus levels were only slightly higher in aged animals by day 3. Although there was a trend of higher titers in respiratory tissues at day 5 post infection, this did not reach statistical significance and virus was cleared from all animals by day 10, regardless of age. CONCLUSIONS: This study provides unique insight into how several parameters of the systemic and mucosal immune response to SARS-CoV infection are significantly modulated by age. These immune differences may contribute to deficient immune function and the observed trend of higher SARS-CoV replication in aged nonhuman primates.",2014 Mar 19,"['Clay, Candice C', 'Donart, Nathan', 'Fomukong, Ndingsa', 'Knight, Jennifer B', 'Overheim, Katie', 'Tipper, Jennifer', 'Van Westrienen, Jesse', 'Hahn, Fletcher', 'Harrod, Kevin S']",Immun Ageing,,,True
b7ff247b83afad127e3d971006647d12ce097d56,PMC,Improving the Diagnosis of Bloodstream Infections: PCR Coupled with Mass Spectrometry,http://dx.doi.org/10.1155/2014/501214,PMC4000954,24818144,CC BY,"The reference method for the diagnosis of bloodstream infections is blood culture followed by biochemical identification and antibiotic susceptibility testing of the isolated pathogen. This process requires 48 to 72 hours. The rapid administration of the most appropriate antimicrobial treatment is crucial for the survival of septic patients; therefore, a rapid method that enables diagnosis directly from analysis of a blood sample without culture is needed. A recently developed platform that couples broad-range PCR amplification of pathogen DNA with electrospray ionization mass spectrometry (PCR/ESI-MS) has the ability to identify virtually any microorganism from direct clinical specimens. To date, two clinical evaluations of the PCR/ESI-MS technology for the diagnosis of bloodstream infections from whole blood have been published. Here we discuss them and describe recent improvements that result in an enhanced sensitivity. Other commercially available assays for the molecular diagnosis of bloodstream infections from whole blood are also reviewed. The use of highly sensitive molecular diagnostic methods in combination with conventional procedures could substantially improve the management of septic patients.",2014 Apr 9,"['Jordana-Lluch, Elena', 'Giménez, Montserrat', 'Quesada, M. Dolores', 'Ausina, Vicente', 'Martró, Elisa']",Biomed Res Int,,,True
28564e89afd6423e291c68867dd52654258b29f8,PMC,How integration of global omics-data could help preparing for pandemics – a scent of influenza,http://dx.doi.org/10.3389/fgene.2014.00080,PMC4000993,24795745,CC BY,"Pandemics caused by novel emerging or re-emerging infectious diseases could lead to high mortality and morbidity world-wide when left uncontrolled. In this perspective, we evaluate the possibility of integration of global omics-data in order to timely prepare for pandemics. Such an approach requires two major innovations. First, data that is obtained should be shared with the global community instantly. The strength of rapid integration of simple signals is exemplified by Google’s(TM) Flu Trend, which could predict the incidence of influenza-like illness based on online search engine queries. Second, omics technologies need to be fast and high-throughput. We postulate that analysis of the exhaled breath would be a simple, rapid and non-invasive alternative. Breath contains hundreds of volatile organic compounds that are altered by infection and inflammation. The molecular fingerprint of breath (breathprint) can be obtained using an electronic nose, which relies on sensor technology. These breathprints can be stored in an online database (a “breathcloud”) and coupled to clinical data. Comparison of the breathprint of a suspected subject to the breathcloud allows for a rapid decision on the presence or absence of a pathogen.",2014 Apr 22,"['Bos, Lieuwe D. J.', 'de Jong, Menno D.', 'Sterk, Peter J.', 'Schultz, Marcus J.']",Front Genet,,,True
1f7f414d82475a8c5b2272163e6f31b474904486,PMC,Emerging gene editing strategies for Duchenne muscular dystrophy targeting stem cells,http://dx.doi.org/10.3389/fphys.2014.00148,PMC4001063,24795643,CC BY,"The progressive loss of muscle mass characteristic of many muscular dystrophies impairs the efficacy of most of the gene and molecular therapies currently being pursued for the treatment of those disorders. It is becoming increasingly evident that a therapeutic application, to be effective, needs to target not only mature myofibers, but also muscle progenitors cells or muscle stem cells able to form new muscle tissue and to restore myofibers lost as the result of the diseases or during normal homeostasis so as to guarantee effective and lost lasting effects. Correction of the genetic defect using oligodeoxynucleotides (ODNs) or engineered nucleases holds great potential for the treatment of many of the musculoskeletal disorders. The encouraging results obtained by studying in vitro systems and model organisms have set the groundwork for what is likely to become an emerging field in the area of molecular and regenerative medicine. Furthermore, the ability to isolate and expand from patients various types of muscle progenitor cells capable of committing to the myogenic lineage provides the opportunity to establish cell lines that can be used for transplantation following ex vivo manipulation and expansion. The purpose of this article is to provide a perspective on approaches aimed at correcting the genetic defect using gene editing strategies and currently under development for the treatment of Duchenne muscular dystrophy (DMD), the most sever of the neuromuscular disorders. Emphasis will be placed on describing the potential of using the patient own stem cell as source of transplantation and the challenges that gene editing technologies face in the field of regenerative biology.",2014 Apr 21,"Bertoni, Carmen",Front Physiol,,,True
8c433501a618d6a3f93463393f4ce58007abec95,PMC,Malaria vaccines: high-throughput tools for antigens discovery with potential for their development,,PMC4002024,24892459,CC BY,"Malaria is a disease induced by parasites of the Plasmodium genus, which are transmitted by Anopheles mosquitoes and represents a great socio-economic burden Worldwide. Plasmodium vivax is the second species of malaria Worldwide, but it is the most prevalent in Latin America and other regions of the planet. It is currently considered that vaccines represent a cost-effective strategy for controlling transmissible diseases and could complement other malaria control measures; however, the chemical and immunological complexity of the parasite has hindered development of effective vaccines. Recent availability of several genomes of Plasmodium species, as well as bioinformatic tools are allowing the selection of large numbers of proteins and analysis of their immune potential. Herein, we review recently developed strategies for discovery of novel antigens with potential for malaria vaccine development.",,"['Céspedes, Nora', 'Vallejo, Andrés', 'Arévalo-Herrera, Myriam', 'Herrera, Sócrates']",Colomb Med (Cali).; 44(2):121-128,,,True
8eb469fc4a148699ffdf0969e3ea75048412472d,PMC,The YXXΦ motif within the severe acute respiratory syndrome coronavirus (SARS-CoV) 3a protein is crucial for its intracellular transport,http://dx.doi.org/10.1186/1743-422X-11-75,PMC4004515,24762043,CC BY,"BACKGROUND: The SARS coronavirus (SARS-CoV) 3a protein functions as an ion channel, induces apoptosis and is important for viral pathogenesis. It is expressed on the cell surface and contains a tyrosine-based sorting motif and a di-acidic motif, which may be crucial for its intracellular trafficking. However the role of these motifs is not fully understood in the case of 3a protein. METHODS: The subcellular distribution of the 3a protein was studied by immunofluorescence staining of cells transfected with wild type and mutant constructs along with markers for different intracellular compartments. Semi-quantitative RT-PCR was performed to estimate the mRNA where as western blotting was carried out to detect protein levels of wild type and mutant 3a proteins. In vitro transcription- translation was performed to estimate cell free protein synthesis. RESULTS: While the wild type 3a protein is efficiently transported to the plasma membrane, the protein with mutations in the tyrosine and valine residues within the YXXV motif (ΔYXXΦ) accumulated in the Golgi compartment. However the 3a protein with mutations within the EXD di-acidic motif (ΔEXD) showed an intracellular distribution similar to the wild type protein. Increased retention of the ΔYXXΦ protein in the Golgi compartment also increased its association with lipid droplets. The ΔYXXΦ protein also expressed at significantly lower levels compared to the wild type 3a protein, which was reversed with Brefeldin A and Aprotinin. CONCLUSIONS: The data suggest that the YXXΦ motif of the SARS-CoV 3a protein is necessary for Golgi to plasma membrane transport, in the absence of which the protein is targeted to lysosomal degradation compartment via lipid droplets.",2014 Apr 24,"['Minakshi, Rinki', 'Padhan, Kartika']",Virol J,,,True
1f2bbc79b56c51c0ae26ced2d7d8ccf10360fa72,PMC,Ribonuclease L and metal-ion–independent endoribonuclease cleavage sites in host and viral RNAs,http://dx.doi.org/10.1093/nar/gku118,PMC4005677,24500209,CC BY,"Ribonuclease L (RNase L) is a metal-ion–independent endoribonuclease associated with antiviral and antibacterial defense, cancer and lifespan. Despite the biological significance of RNase L, the RNAs cleaved by this enzyme are poorly defined. In this study, we used deep sequencing methods to reveal the frequency and location of RNase L cleavage sites within host and viral RNAs. To make cDNA libraries, we exploited the 2′, 3′-cyclic phosphate at the end of RNA fragments produced by RNase L and other metal-ion–independent endoribonucleases. We optimized and validated 2′, 3′-cyclic phosphate cDNA synthesis and Illumina sequencing methods using viral RNAs cleaved with purified RNase L, viral RNAs cleaved with purified RNase A and RNA from uninfected and poliovirus-infected HeLa cells. Using these methods, we identified (i) discrete regions of hepatitis C virus and poliovirus RNA genomes that were profoundly susceptible to RNase L and other single-strand specific endoribonucleases, (ii) RNase L-dependent and RNase L-independent cleavage sites within ribosomal RNAs (rRNAs) and (iii) 2′, 3′-cyclic phosphates at the ends of 5S rRNA and U6 snRNA. Monitoring the frequency and location of metal-ion–independent endoribonuclease cleavage sites within host and viral RNAs reveals, in part, how these enzymes contribute to health and disease.",2014 Apr 5,"['Cooper, Daphne A.', 'Jha, Babal K.', 'Silverman, Robert H.', 'Hesselberth, Jay R.', 'Barton, David J.']",Nucleic Acids Res,,,True
ae0b9375dd56b6338cb63a3b5857e4125f5edf41,PMC,Ribonuclease L and metal-ion–independent endoribonuclease cleavage sites in host and viral RNAs,http://dx.doi.org/10.1093/nar/gku118,PMC4005677,24500209,CC BY,"Ribonuclease L (RNase L) is a metal-ion–independent endoribonuclease associated with antiviral and antibacterial defense, cancer and lifespan. Despite the biological significance of RNase L, the RNAs cleaved by this enzyme are poorly defined. In this study, we used deep sequencing methods to reveal the frequency and location of RNase L cleavage sites within host and viral RNAs. To make cDNA libraries, we exploited the 2′, 3′-cyclic phosphate at the end of RNA fragments produced by RNase L and other metal-ion–independent endoribonucleases. We optimized and validated 2′, 3′-cyclic phosphate cDNA synthesis and Illumina sequencing methods using viral RNAs cleaved with purified RNase L, viral RNAs cleaved with purified RNase A and RNA from uninfected and poliovirus-infected HeLa cells. Using these methods, we identified (i) discrete regions of hepatitis C virus and poliovirus RNA genomes that were profoundly susceptible to RNase L and other single-strand specific endoribonucleases, (ii) RNase L-dependent and RNase L-independent cleavage sites within ribosomal RNAs (rRNAs) and (iii) 2′, 3′-cyclic phosphates at the ends of 5S rRNA and U6 snRNA. Monitoring the frequency and location of metal-ion–independent endoribonuclease cleavage sites within host and viral RNAs reveals, in part, how these enzymes contribute to health and disease.",2014 Apr 5,"['Cooper, Daphne A.', 'Jha, Babal K.', 'Silverman, Robert H.', 'Hesselberth, Jay R.', 'Barton, David J.']",Nucleic Acids Res,,,True
31a744d5cdf4b8901ea26a847bbc3cc76d6e02d7,PMC,"Molecular and serological surveillance of canine enteric viruses in stray dogs from Vila do Maio, Cape Verde",http://dx.doi.org/10.1186/1746-6148-10-91,PMC4005843,24755118,CC BY,"BACKGROUND: Infections caused by canine parvovirus, canine distemper virus and canine coronavirus are an important cause of mortality and morbidity in dogs worldwide. Prior to this study, no information was available concerning the incidence and prevalence of these viruses in Cape Verde archipelago. RESULTS: To provide information regarding the health status of the canine population in Vila do Maio, Maio Island, Cape Verde, 53 rectal swabs were collected from 53 stray dogs during 2010 and 93 rectal swabs and 88 blood samples were collected from 125 stray dogs in 2011. All rectal swabs (2010 n = 53; 2011 n = 93) were analysed for the presence of canine parvovirus, canine distemper virus and canine coronavirus nucleic acids by quantitative PCR methods. Specific antibodies against canine distemper virus and canine parvovirus were also assessed (2011 n = 88). From the 2010 sampling, 43.3% (23/53) were positive for canine parvovirus DNA, 11.3% (6/53) for canine distemper virus RNA and 1.9% (1/53) for canine coronavirus RNA. In 2011, the prevalence values for canine parvovirus and canine coronavirus were quite similar to those from the previous year, respectively 44.1% (41/93), and 1.1% (1/93), but canine distemper virus was not detected in any of the samples analysed (0%, 0/93). Antibodies against canine parvovirus were detected in 71.6% (63/88) blood samples and the seroprevalence found for canine distemper virus was 51.1% (45/88). CONCLUSIONS: This study discloses the data obtained in a molecular and serological epidemiological surveillance carried out in urban populations of stray and domestic animals. Virus transmission and spreading occurs easily in large dog populations leading to high mortality rates particularly in unvaccinated susceptible animals. In addition, these animals can act as disease reservoirs for wild animal populations by occasional contact. Identification of susceptible wildlife of Maio Island is of upmost importance to evaluate the risk of pathogen spill over from domestic to wild animals in Cape Verde and to evaluate the associated threat to the wild susceptible species.",2014 Apr 23,"['Castanheira, Pedro', 'Duarte, Ana', 'Gil, Solange', 'Cartaxeiro, Clara', 'Malta, Manuel', 'Vieira, Sara', 'Tavares, Luis']",BMC Vet Res,,,True
9e5c4cfb4582c7aa5e60455ae948554981054c47,PMC,Lung ultrasound for the diagnosis of pneumonia in adults: a systematic review and meta-analysis,http://dx.doi.org/10.1186/1465-9921-15-50,PMC4005846,24758612,CC BY,"BACKGROUND: Guidelines do not currently recommend the use of lung ultrasound (LUS) as an alternative to chest X-ray (CXR) or chest computerized tomography (CT) scan for the diagnosis of pneumonia. We conducted a meta-analysis to summarize existing evidence of the diagnostic accuracy of LUS for pneumonia in adults. METHODS: We conducted a systematic search of published studies comparing the diagnostic accuracy of LUS against a referent CXR or chest CT scan and/or clinical criteria for pneumonia in adults aged ≥18 years. Eligible studies were required to have a CXR and/or chest CT scan at the time of evaluation. We manually extracted descriptive and quantitative information from eligible studies, and calculated pooled sensitivity and specificity using the Mantel-Haenszel method and pooled positive and negative likelihood ratios (LR) using the DerSimonian-Laird method. We assessed for heterogeneity using the Q and I(2) statistics. RESULTS: Our initial search strategy yielded 2726 articles, of which 45 (1.7%) were manually selected for review and 10 (0.4%) were eligible for analyses. These 10 studies provided a combined sample size of 1172 participants. Six studies enrolled adult patients who were either hospitalized or admitted to Emergency Departments with suspicion of pneumonia and 4 studies enrolled critically-ill adult patients. LUS was performed by highly-skilled sonographers in seven studies, by trained physicians in two, and one did not mention level of training. All studies were conducted in high-income settings. LUS took a maximum of 13 minutes to conduct. Nine studies used a 3.5-5 MHz micro-convex transducer and one used a 5–9 MHz convex probe. Pooled sensitivity and specificity for the diagnosis of pneumonia using LUS were 94% (95% CI, 92%-96%) and 96% (94%-97%), respectively; pooled positive and negative LRs were 16.8 (7.7-37.0) and 0.07 (0.05-0.10), respectively; and, the area-under-the-ROC curve was 0.99 (0.98-0.99). CONCLUSIONS: Our meta-analysis supports that LUS, when conducted by highly-skilled sonographers, performs well for the diagnosis of pneumonia. General practitioners and Emergency Medicine physicians should be encouraged to learn LUS since it appears to be an established diagnostic tool in the hands of experienced physicians.",2014 Apr 23,"['Chavez, Miguel A', 'Shams, Navid', 'Ellington, Laura E', 'Naithani, Neha', 'Gilman, Robert H', 'Steinhoff, Mark C', 'Santosham, Mathuram', 'Black, Robert E', 'Price, Carrie', 'Gross, Margaret', 'Checkley, William']",Respir Res,,,True
a279441c0873b6bfdfbd63cee1220cf9596acaee,PMC,A dose and time response Markov model for the in-host dynamics of infection with intracellular bacteria following inhalation: with application to Francisella tularensis,http://dx.doi.org/10.1098/rsif.2014.0119,PMC4006251,24671937,CC BY,"In a novel approach, the standard birth–death process is extended to incorporate a fundamental mechanism undergone by intracellular bacteria, phagocytosis. The model accounts for stochastic interaction between bacteria and cells of the immune system and heterogeneity in susceptibility to infection of individual hosts within a population. Model output is the dose–response relation and the dose-dependent distribution of time until response, where response is the onset of symptoms. The model is thereafter parametrized with respect to the highly virulent Schu S4 strain of Francisella tularensis, in the first such study to consider a biologically plausible mathematical model for early human infection with this bacterium. Results indicate a median infectious dose of about 23 organisms, which is higher than previously thought, and an average incubation period of between 3 and 7 days depending on dose. The distribution of incubation periods is right-skewed up to about 100 organisms and symmetric for larger doses. Moreover, there are some interesting parallels to the hypotheses of some of the classical dose–response models, such as independent action (single-hit model) and individual effective dose (probit model). The findings of this study support experimental evidence and postulations from other investigations that response is, in fact, influenced by both in-host and between-host variability.",2014 Jun 6,"['Wood, R. M.', 'Egan, J. R.', 'Hall, I. M.']",J R Soc Interface,,,True
3bb7cd6590ad3a1d77205ad58c2c014934ee2364,PMC,Amino acid changes in the spike protein of feline coronavirus correlate with systemic spread of virus from the intestine and not with feline infectious peritonitis,http://dx.doi.org/10.1186/1297-9716-45-49,PMC4006447,24767677,CC BY,"Recent evidence suggests that a mutation in the spike protein gene of feline coronavirus (FCoV), which results in an amino acid change from methionine to leucine at position 1058, may be associated with feline infectious peritonitis (FIP). Tissue and faecal samples collected post mortem from cats diagnosed with or without FIP were subjected to RNA extraction and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) to detect FCoV RNA. In cats with FIP, 95% of tissue, and 81% of faecal samples were PCR-positive, as opposed to 22% of tissue, and 60% of faecal samples in cats without FIP. Relative FCoV copy numbers were significantly higher in the cats with FIP, both in tissues (P < 0.001) and faeces (P = 0.02). PCR-positive samples underwent pyrosequencing encompassing position 1058 of the FCoV spike protein. This identified a methionine codon at position 1058, consistent with the shedding of an enteric form of FCoV, in 77% of the faecal samples from cats with FIP, and in 100% of the samples from cats without FIP. In contrast, 91% of the tissue samples from cats with FIP and 89% from cats without FIP had a leucine codon at position 1058, consistent with a systemic form of FCoV. These results suggest that the methionine to leucine substitution at position 1058 in the FCoV spike protein is indicative of systemic spread of FCoV from the intestine, rather than a virus with the potential to cause FIP.",2014 Apr 25,"['Porter, Emily', 'Tasker, Séverine', 'Day, Michael J', 'Harley, Ross', 'Kipar, Anja', 'Siddell, Stuart G', 'Helps, Christopher R']",Vet Res,,,True
25e53f84ee9bb3d0f9be47a740938c12dbbd559b,PMC,"Evaluation of Antiviral Efficacy of Ribavirin, Arbidol, and T-705 (Favipiravir) in a Mouse Model for Crimean-Congo Hemorrhagic Fever",http://dx.doi.org/10.1371/journal.pntd.0002804,PMC4006714,24786461,CC BY,"BACKGROUND: Mice lacking the type I interferon receptor (IFNAR(−/−) mice) reproduce relevant aspects of Crimean-Congo hemorrhagic fever (CCHF) in humans, including liver damage. We aimed at characterizing the liver pathology in CCHF virus-infected IFNAR(−/−) mice by immunohistochemistry and employed the model to evaluate the antiviral efficacy of ribavirin, arbidol, and T-705 against CCHF virus. METHODOLOGY/PRINCIPAL FINDINGS: CCHF virus-infected IFNAR(−/−) mice died 2–6 days post infection with elevated aminotransferase levels and high virus titers in blood and organs. Main pathological alteration was acute hepatitis with extensive bridging necrosis, reactive hepatocyte proliferation, and mild to moderate inflammatory response with monocyte/macrophage activation. Virus-infected and apoptotic hepatocytes clustered in the necrotic areas. Ribavirin, arbidol, and T-705 suppressed virus replication in vitro by ≥3 log units (IC(50) 0.6–2.8 µg/ml; IC(90) 1.2–4.7 µg/ml). Ribavirin [100 mg/(kg×d)] did not increase the survival rate of IFNAR(−/−) mice, but prolonged the time to death (p<0.001) and reduced the aminotransferase levels and the virus titers. Arbidol [150 mg/(kg×d)] had no efficacy in vivo. Animals treated with T-705 at 1 h [15, 30, and 300 mg/(kg×d)] or up to 2 days [300 mg/(kg×d)] post infection survived, showed no signs of disease, and had no virus in blood and organs. Co-administration of ribavirin and T-705 yielded beneficial rather than adverse effects. CONCLUSIONS/SIGNIFICANCE: Activated hepatic macrophages and monocyte-derived cells may play a role in the proinflammatory cytokine response in CCHF. Clustering of infected hepatocytes in necrotic areas without marked inflammation suggests viral cytopathic effects. T-705 is highly potent against CCHF virus in vitro and in vivo. Its in vivo efficacy exceeds that of the current standard drug for treatment of CCHF, ribavirin.",2014 May 1,"['Oestereich, Lisa', 'Rieger, Toni', 'Neumann, Melanie', 'Bernreuther, Christian', 'Lehmann, Maria', 'Krasemann, Susanne', 'Wurr, Stephanie', 'Emmerich, Petra', 'de Lamballerie, Xavier', 'Ölschläger, Stephan', 'Günther, Stephan']",PLoS Negl Trop Dis,,,True
893e7344ac32678f26385d12f05ab2a06ed3544c,PMC,Emerging Infectious Diseases in Free-Ranging Wildlife–Australian Zoo Based Wildlife Hospitals Contribute to National Surveillance,http://dx.doi.org/10.1371/journal.pone.0095127,PMC4006786,24787430,CC BY,"Emerging infectious diseases are increasingly originating from wildlife. Many of these diseases have significant impacts on human health, domestic animal health, and biodiversity. Surveillance is the key to early detection of emerging diseases. A zoo based wildlife disease surveillance program developed in Australia incorporates disease information from free-ranging wildlife into the existing national wildlife health information system. This program uses a collaborative approach and provides a strong model for a disease surveillance program for free-ranging wildlife that enhances the national capacity for early detection of emerging diseases.",2014 May 1,"['Cox-Witton, Keren', 'Reiss, Andrea', 'Woods, Rupert', 'Grillo, Victoria', 'Baker, Rupert T.', 'Blyde, David J.', 'Boardman, Wayne', 'Cutter, Stephen', 'Lacasse, Claude', 'McCracken, Helen', 'Pyne, Michael', 'Smith, Ian', 'Vitali, Simone', 'Vogelnest, Larry', 'Wedd, Dion', 'Phillips, Martin', 'Bunn, Chris', 'Post, Lyndel']",PLoS One,,,True
a820465dbd9b10702c009445daa65b9bd48e0c72,PMC,Comparison of the Effects of Air Pollution on Outpatient and Inpatient Visits for Asthma: A Population-Based Study in Taiwan,http://dx.doi.org/10.1371/journal.pone.0096190,PMC4006842,24789041,CC BY,"BACKGROUND: A nationwide asthma survey on the effects of air pollution is lacking in Taiwan. The purpose of this study was to evaluate the time trend and the relationship between air pollution and health care services for asthma in Taiwan. METHODS: Health care services for asthma and ambient air pollution data were obtained from the National Health Insurance Research database and Environmental Protection Administration from 2000 through 2009, respectively. Health care services, including those related to the outpatient and inpatient visits were compared according to the concentration of air pollutants. RESULTS: The number of asthma-patient visits to health-care facilities continue to increase in Taiwan. Relative to the respective lowest quartile of air pollutants, the adjusted relative risks (RRs) of the outpatient visits in the highest quartile were 1.10 (P-trend = 0.013) for carbon monoxide (CO), 1.10 (P-trend = 0.015) for nitrogen dioxide (NO(2)), and 1.20 (P-trend <0.0001) for particulate matter with an aerodynamic diameter ≦10µm (PM(10)) in the child group (aged 0–18). For adults aged 19–44, the RRs of outpatient visits were 1.13 (P-trend = 0.078) for CO, 1.17 (P-trend = 0.002) for NO(2,) and 1.13 (P-trend <0.0001) for PM(10). For adults aged 45–64, the RRs of outpatient visits were 1.15 (P-trend = 0.003) for CO, 1.19 (P-trend = 0.0002) for NO(2,) and 1.10 (P-trend = 0.001) for PM(10). For the elderly (aged≥ 65), the RRs of outpatient visits in were 1.12 (P-trend = 0.003) for NO(2) and 1.10 (P-trend = 0.006) for PM(10.) For inpatient visits, the RRs across quartiles of CO level were 1.00, 1.70, 1.92, and 1.86 (P-trend = 0.0001) in the child group. There were no significant linear associations between inpatient visits and air pollutants in other groups. CONCLUSIONS: There were positive associations between CO levels and childhood inpatient visits as well as NO(2), CO and PM(10) and outpatient visits.",2014 May 1,"['Pan, Hui-Hsien', 'Chen, Chun-Tzu', 'Sun, Hai-Lun', 'Ku, Min-Sho', 'Liao, Pei-Fen', 'Lu, Ko-Hsiu', 'Sheu, Ji-Nan', 'Huang, Jing-Yang', 'Pai, Jar-Yuan', 'Lue, Ko-Huang']",PLoS One,,,True
4fc5e9665de47ef816e11dea365d068d1d1a77e8,PMC,Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Ion Channel Activity Promotes Virus Fitness and Pathogenesis,http://dx.doi.org/10.1371/journal.ppat.1004077,PMC4006877,24788150,CC BY,"Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC) activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARS-CoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS) leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na(+)/K(+) ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1β were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1β was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS-CoV virulence.",2014 May 1,"['Nieto-Torres, Jose L.', 'DeDiego, Marta L.', 'Verdiá-Báguena, Carmina', 'Jimenez-Guardeño, Jose M.', 'Regla-Nava, Jose A.', 'Fernandez-Delgado, Raul', 'Castaño-Rodriguez, Carlos', 'Alcaraz, Antonio', 'Torres, Jaume', 'Aguilella, Vicente M.', 'Enjuanes, Luis']",PLoS Pathog,,,True
29baaba300edea006f7b4d287edd3426d6573a26,PMC,PARV4: An Emerging Tetraparvovirus,http://dx.doi.org/10.1371/journal.ppat.1004036,PMC4006886,24789326,CC BY,,2014 May 1,"['Matthews, Philippa C.', 'Malik, Amna', 'Simmons, Ruth', 'Sharp, Colin', 'Simmonds, Peter', 'Klenerman, Paul']",PLoS Pathog,,,True
3330a6e81c27b196cb5171baf11239a9560ff6e7,PMC,Respiratory viral pathogens among Singapore military servicemen 2009 – 2012: epidemiology and clinical characteristics,http://dx.doi.org/10.1186/1471-2334-14-204,PMC4006965,24735158,CC BY,"BACKGROUND: Few studies have comprehensively described tropical respiratory disease surveillance in military populations. There is also a lack of studies comparing clinical characteristics of the non-influenza pathogens with influenza and amongst themselves. METHODS: From May 2009 through October 2012, 7733 consenting cases of febrile respiratory illness (FRI) (temperature [greater than or equal to]37.5degreesC with cough or sorethroat) and controls in the Singapore military had clinical data and nasal washes collected prospectively. Nasal washes underwent multiplex PCR, and the analysis was limited to viral mono-infections. RESULTS: 49% of cases tested positive for at least one virus, of whom 10% had multiple infections. 53% of the FRI cases fulfilled the definition of influenza-like illness (ILI), of whom 52% were positive for at least one virus. The most frequent etiologies for mono-infections among FRI cases were Influenza A(H1N1)pdm09 (13%), Influenza B (13%) and coxsackevirus (9%). The sensitivity, specificity, positive predictive value and negative predictive value of ILI for influenza among FRI cases were 72%, 48%, 40% and 69% respectively. On logistic regression, there were marked differences in the prevalence of different symptoms and signs between viruses with fever more prevalent amongst influenza and adenovirus infections than other viruses. CONCLUSION: There are multiple viral etiologies for FRI and ILI with differing clinical symptoms in the Singapore military. Influenza and coxsackevirus were the most common etiology for FRI, while influenza and adenoviruses displayed the most febrile symptoms. Further studies should explore these differences and possible interventions.",2014 Apr 15,"['Tan, Xin Quan', 'Zhao, Xiahong', 'Lee, Vernon J', 'Loh, Jin Phang', 'Tan, Boon Huan', 'Koh, Wee Hong Victor', 'Ng, Sock Hoon', 'Chen, Mark I-Cheng', 'Cook, Alex Richard']",BMC Infect Dis,,,True
b16b23aad25d88c3af9ccd50b754cd4d9e8762fe,PMC,Comparative Analysis of the Effectiveness of Three Immunization Strategies in Controlling Disease Outbreaks in Realistic Social Networks,http://dx.doi.org/10.1371/journal.pone.0095911,PMC4008523,24787718,CC BY,"The high incidence of emerging infectious diseases has highlighted the importance of effective immunization strategies, especially the stochastic algorithms based on local available network information. Present stochastic strategies are mainly evaluated based on classical network models, such as scale-free networks and small-world networks, and thus are insufficient. Three frequently referred stochastic immunization strategies—acquaintance immunization, community-bridge immunization, and ring vaccination—were analyzed in this work. The optimal immunization ratios for acquaintance immunization and community-bridge immunization strategies were investigated, and the effectiveness of these three strategies in controlling the spreading of epidemics were analyzed based on realistic social contact networks. The results show all the strategies have decreased the coverage of the epidemics compared to baseline scenario (no control measures). However the effectiveness of acquaintance immunization and community-bridge immunization are very limited, with acquaintance immunization slightly outperforming community-bridge immunization. Ring vaccination significantly outperforms acquaintance immunization and community-bridge immunization, and the sensitivity analysis shows it could be applied to controlling the epidemics with a wide infectivity spectrum. The effectiveness of several classical stochastic immunization strategies was evaluated based on realistic contact networks for the first time in this study. These results could have important significance for epidemic control research and practice.",2014 May 2,"['Xu, Zhijing', 'Zu, Zhenghu', 'Zheng, Tao', 'Zhang, Wendou', 'Xu, Qing', 'Liu, Jinjie']",PLoS One,,,True
df63d7e1d02197e9dc6686976729bb00682f2ff8,PMC,EV71 vaccines: a milestone in the history of global vaccine development,http://dx.doi.org/10.1038/emi.2014.29,PMC4008769,26038519,CC BY,,2014 Apr 16,"Lu, Shan",Emerg Microbes Infect,,,True
1713f0cf6cf8f5e4134cb4b78d5ab4d2c3cc8791,PMC,Herpes Simplex Virus Hepatitis in an Immunocompetent Adult: A Fatal Outcome due to Liver Failure,http://dx.doi.org/10.1155/2011/138341,PMC4010022,24826316,CC BY,"Objective. To present a case of a healthy 41-year-old female who developed fulminant hepatic failure leading to death. The cause of hepatic failure identified on postmortem exam was herpes simplex virus hepatitis. Design. Observation of a single patient. Setting. Intensive care unit of a tertiary care university teaching hospital in Canada. Patient. 41-year-old previously healthy female presenting with a nonspecific viral illness and systemic inflammatory response syndrome. Intervention. The patient was treated with intravenous fluids and broad-spectrum antibiotics. On the second day of admission, she was found to have elevated transaminases, and, over 48 hours, she progressed to fulminant liver failure with disseminated intravascular coagulopathy, refractory lactic acidosis, and shock. She progressed to respiratory failure requiring intubation and mechanical ventilation. She was started on N-acetylcysteine, a bicarbonate infusion, hemodialysis, and multiple vasopressors and inotropes. Measurements and Main Results. Despite treatment, the patient died roughly 70 hours after her initial presentation to hospital. Her postmortem liver biopsy revealed herpes simplex virus hepatitis as her cause of death. Conclusions. Herpes simplex virus must be considered in all patients presenting with liver failure of unknown cause. If suspected, prompt treatment with acyclovir should be initiated.",2011 Dec 7,"['Poley, Rachel A.', 'Snowdon, Jaime F.', 'Howes, Daniel W.']",Case Rep Crit Care,,,True
4d601f59175ab8d983670ce69504c80be6fb38a4,PMC,Epidemiology of Acute Respiratory Infections in Children in Guangzhou: A Three-Year Study,http://dx.doi.org/10.1371/journal.pone.0096674,PMC4010508,24797911,CC BY,"Acute Respiratory Infections (ARI) are some of the most common human diseases worldwide. However, they have a complex and diverse etiology, and the characteristics of the pathogens involved in respiratory infections in developing countries are not well understood. In this work, we analyzed the characteristics of 17 common respiratory pathogens in children (≤14 years old) with ARI in Guangzhou, southern China over a 3-year period using real-time polymerase chain reaction. Pathogens were identified in 2361/4242 (55.7%) patients, and the positivity rate varied seasonally. Ten of the 17 pathogens investigated showed positivity rates of more than 5%. The most frequently detected pathogens were respiratory syncytial virus (768/2361, 32.5%), influenza A virus (428/2361, 18.1%), enterovirus (138/2361, 13.3%), Mycoplasma pneumoniae (267/2361, 11.3%) and adenovirus (213/2361, 9.0%). Co-pathogens were common and found in 503 of 2361 (21.3%) positive samples. When ranked according to frequency of occurrence, the pattern of co-pathogens was similar to that of the primary pathogens, with the exception of human bocavirus, human coronavirus and human metapneumovirus. Significant differences were found in age prevalence in 10 of the 17 pathogens (p≤0.009): four basic patterns were observed, A: detection rates increased with age, B: detection rates declined with age, C: the detection rate showed distinct peaks or D: numbers of patients were too low to detect a trend or showed no significant difference among age groups (p>0.05). These data will be useful for planning vaccine research and control strategies and for studies predicting pathogen prevalence.",2014 May 5,"['Liu, Wen Kuan', 'Liu, Qian', 'Chen, De Hui', 'Liang, Huan Xi', 'Chen, Xiao Kai', 'Chen, Mei Xin', 'Qiu, Shu Yan', 'Yang, Zi Yeng', 'Zhou, Rong']",PLoS One,,,True
ecea1d9607209bfcf32da251f53136e7f5c12f3e,PMC,A Vaccine of L2 Epitope Repeats Fused with a Modified IgG1 Fc Induced Cross-Neutralizing Antibodies and Protective Immunity against Divergent Human Papillomavirus Types,http://dx.doi.org/10.1371/journal.pone.0095448,PMC4011685,24802101,CC BY,"Current human papillomavirus (HPV) major capsid protein L1 virus-like particles (VLPs)-based vaccines in clinic induce strong HPV type-specific neutralizing antibody responses. To develop pan-HPV vaccines, here, we show that the fusion protein E3R4 consisting of three repeats of HPV16 L2 aa 17–36 epitope (E3) and a modified human IgG1 Fc scaffold (R4) induces cross-neutralizing antibodies and protective immunity against divergent HPV types. E3R4 was expressed as a secreted protein in baculovirus expression system and could be simply purified by one step Protein A affinity chromatography with the purity above 90%. Vaccination of E3R4 formulated with Freunds adjuvant not only induced cross-neutralizing antibodies against HPV pseudovirus types 16, 18, 45, 52, 58, 6, 11 and 5 in mice, but also protected mice against vaginal challenges with HPV pseudovirus types 16, 45, 52, 58, 11 and 5 for at least eleven months after the first immunization. Moreover, vaccination of E3R4 formulated with FDA approved adjuvant alum plus monophosphoryl lipid A also induced cross-neutralizing antibodies against HPV types 16, 18 and 6 in rabbits. Thus, our results demonstrate that delivery of L2 antigen as a modified Fc-fusion protein may facilitate pan-HPV vaccine development.",2014 May 6,"['Chen, Xue', 'Liu, Hongyang', 'Zhang, Ting', 'Liu, Yanchun', 'Xie, Xixiu', 'Wang, Zhirong', 'Xu, Xuemei']",PLoS One,,,True
dc2451c2166ef31db7fc2ad93ade6bf4d18c55e2,PMC,Insights and Ideas Garnered from Marine Metabolites for Development of Dual-Function Acetylcholinesterase and Amyloid-β Aggregation Inhibitors,http://dx.doi.org/10.3390/md12042114,PMC4012451,24714126,CC BY,"Due to the diversity of biological activities that can be found in aquatic ecosystems, marine metabolites have been an active area of drug discovery for the last 30 years. Marine metabolites have been found to inhibit a number of enzymes important in the treatment of human disease. Here, we focus on marine metabolites that inhibit the enzyme acetylcholinesterase, which is the cellular target for treatment of early-stage Alzheimer’s disease. Currently, development of anticholinesterase drugs with improved potency, and drugs that act as dual acetylcholinesterase and amyloid-β aggregation inhibitors, are being sought to treat Alzheimer’s disease. Seven classes of marine metabolites are reported to possess anti-cholinesterase activity. We compared these metabolites to clinically-used acetylcholinesterase inhibitors having known mechanisms of inhibition. We performed a docking simulation and compared them to published experimental data for each metabolite to determine the most likely mechanism of inhibition for each class of marine inhibitor. Our results indicate that several marine metabolites bind to regions of the acetylcholinesterase active site that are not bound by the clinically-used drugs rivastigmine, galanthamine, donepezil, or tacrine. We use the novel poses adopted for computational drug design of tighter binding anticholinesterase drugs likely to act as inhibitors of both acetylcholinesterase activity and amyloid-β aggregation inhibition.",2014 Apr 4,"['Stoddard, Shana V.', 'Hamann, Mark T.', 'Wadkins, Randy M.']",Mar Drugs,,,True
0c490bb2b4f44038ed03a197923aa3490e54f75b,PMC,Insights and Ideas Garnered from Marine Metabolites for Development of Dual-Function Acetylcholinesterase and Amyloid-β Aggregation Inhibitors,http://dx.doi.org/10.3390/md12042114,PMC4012451,24714126,CC BY,"Due to the diversity of biological activities that can be found in aquatic ecosystems, marine metabolites have been an active area of drug discovery for the last 30 years. Marine metabolites have been found to inhibit a number of enzymes important in the treatment of human disease. Here, we focus on marine metabolites that inhibit the enzyme acetylcholinesterase, which is the cellular target for treatment of early-stage Alzheimer’s disease. Currently, development of anticholinesterase drugs with improved potency, and drugs that act as dual acetylcholinesterase and amyloid-β aggregation inhibitors, are being sought to treat Alzheimer’s disease. Seven classes of marine metabolites are reported to possess anti-cholinesterase activity. We compared these metabolites to clinically-used acetylcholinesterase inhibitors having known mechanisms of inhibition. We performed a docking simulation and compared them to published experimental data for each metabolite to determine the most likely mechanism of inhibition for each class of marine inhibitor. Our results indicate that several marine metabolites bind to regions of the acetylcholinesterase active site that are not bound by the clinically-used drugs rivastigmine, galanthamine, donepezil, or tacrine. We use the novel poses adopted for computational drug design of tighter binding anticholinesterase drugs likely to act as inhibitors of both acetylcholinesterase activity and amyloid-β aggregation inhibition.",2014 Apr 4,"['Stoddard, Shana V.', 'Hamann, Mark T.', 'Wadkins, Randy M.']",Mar Drugs,,,False
d2d7428869cef29308728dd3a05f0facaf1d25da,PMC,SARS-CoV envelope protein palmitoylation or nucleocapid association is not required for promoting virus-like particle production,http://dx.doi.org/10.1186/1423-0127-21-34,PMC4014084,24766657,CC BY,"BACKGROUND: Coronavirus membrane (M) proteins are capable of interacting with nucleocapsid (N) and envelope (E) proteins. Severe acute respiratory syndrome coronavirus (SARS-CoV) M co-expression with either N or E is sufficient for producing virus-like particles (VLPs), although at a lower level compared to M, N and E co-expression. Whether E can release from cells or E/N interaction exists so as to contribute to enhanced VLP production is unknown. It also remains to be determined whether E palmitoylation or disulfide bond formation plays a role in SARS-CoV virus assembly. RESULTS: SARS-CoV N is released from cells through an association with E protein-containing vesicles. Further analysis suggests that domains involved in E/N interaction are largely located in both carboxyl-terminal regions. Changing all three E cysteine residues to alanines did not exert negative effects on E release, E association with N, or E enhancement of VLP production, suggesting that E palmitoylation modification or disulfide bond formation is not required for SARS-CoV virus assembly. We found that removal of the last E carboxyl-terminal residue markedly affected E release, N association, and VLP incorporation, but did not significantly compromise the contribution of E to efficient VLP production. CONCLUSIONS: The independence of the SARS-CoV E enhancement effect on VLP production from its viral packaging capacity suggests a distinct SARS-CoV E role in virus assembly.",2014 Apr 27,"['Tseng, Ying-Tzu', 'Wang, Shiu-Mei', 'Huang, Kuo-Jung', 'Wang, Chin-Tien']",J Biomed Sci,,,True
051cf89045450e5eff3fc9ba4fdc518fe1d623b8,PMC,Structural basis of sialidase in complex with geranylated flavonoids as potent natural inhibitors,http://dx.doi.org/10.1107/S1399004714002971,PMC4014123,24816104,CC BY,"Sialidase catalyzes the removal of a terminal sialic acid from glycoconjugates and plays a pivotal role in nutrition, cellular interactions and pathogenesis mediating various infectious diseases including cholera, influenza and sepsis. An array of antiviral sialidase agents have been developed and are commercially available, such as zanamivir and oseltamivir for treating influenza. However, the development of bacterial sialidase inhibitors has been much less successful. Here, natural polyphenolic geranylated flavonoids which show significant inhibitory effects against Cp-NanI, a sialidase from Clostridium perfringens, are reported. This bacterium causes various gastrointestinal diseases. The crystal structure of the Cp-NanI catalytic domain in complex with the best inhibitor, diplacone, is also presented. This structure explains how diplacone generates a stable enzyme–inhibitor complex. These results provide a structural framework for understanding the interaction between sialidase and natural flavonoids, which are promising scaffolds on which to discover new anti-sialidase agents.",2014 Apr 30,"['Lee, Youngjin', 'Ryu, Young Bae', 'Youn, Hyung-Seop', 'Cho, Jung Keun', 'Kim, Young Min', 'Park, Ji-Young', 'Lee, Woo Song', 'Park, Ki Hun', 'Eom, Soo Hyun']",Acta Crystallogr D Biol Crystallogr,,,True
bfa53450da2024fe53e99a919dcadd4f9740a774,PMC,Structural basis of sialidase in complex with geranylated flavonoids as potent natural inhibitors,http://dx.doi.org/10.1107/S1399004714002971,PMC4014123,24816104,CC BY,"Sialidase catalyzes the removal of a terminal sialic acid from glycoconjugates and plays a pivotal role in nutrition, cellular interactions and pathogenesis mediating various infectious diseases including cholera, influenza and sepsis. An array of antiviral sialidase agents have been developed and are commercially available, such as zanamivir and oseltamivir for treating influenza. However, the development of bacterial sialidase inhibitors has been much less successful. Here, natural polyphenolic geranylated flavonoids which show significant inhibitory effects against Cp-NanI, a sialidase from Clostridium perfringens, are reported. This bacterium causes various gastrointestinal diseases. The crystal structure of the Cp-NanI catalytic domain in complex with the best inhibitor, diplacone, is also presented. This structure explains how diplacone generates a stable enzyme–inhibitor complex. These results provide a structural framework for understanding the interaction between sialidase and natural flavonoids, which are promising scaffolds on which to discover new anti-sialidase agents.",2014 Apr 30,"['Lee, Youngjin', 'Ryu, Young Bae', 'Youn, Hyung-Seop', 'Cho, Jung Keun', 'Kim, Young Min', 'Park, Ji-Young', 'Lee, Woo Song', 'Park, Ki Hun', 'Eom, Soo Hyun']",Acta Crystallogr D Biol Crystallogr,,,False
f6069d299d3a03300b5ce41868efc5f2391a7544,PMC,Cellular Superspreaders: An Epidemiological Perspective on HIV Infection inside the Body,http://dx.doi.org/10.1371/journal.ppat.1004092,PMC4014458,24811311,CC BY,,2014 May 8,"['Talbert-Slagle, Kristina', 'Atkins, Katherine E.', 'Yan, Koon-Kiu', 'Khurana, Ekta', 'Gerstein, Mark', 'Bradley, Elizabeth H.', 'Berg, David', 'Galvani, Alison P.', 'Townsend, Jeffrey P.']",PLoS Pathog,,,True
ba2fc738765a5e090d04ad70d972bb35724d927a,PMC,Haemoproteus iwa in Great Frigatebirds (Fregata minor) in the Islands of the Western Indian Ocean,http://dx.doi.org/10.1371/journal.pone.0097185,PMC4014603,24810172,CC BY,"Blood parasites of the sub-genus Haemoproteus have been reported in seabirds, in particular in species in the Suliformes order. These parasites are transmitted by hippoboscid flies of the genus Olfersia; strong specificity has been suggested between the vector and its vertebrate host. We investigated the prevalence of Haemoproteus infection in Suliformes and hippoboscid flies in two oceanic islands of the Western Indian Ocean: Europa and Tromelin. In total, 209 blood samples were collected from great frigatebirds (Fregata minor), masked boobies (Sula dactylatra) and red-footed boobies (Sula sula). Forty-one hippoboscid flies were also collected from birds. Seventeen frigatebirds and one fly collected on Europa tested positive for the presence of Haemoproteus parasites by polymerase chain reaction. Phylogenetic analyses based on partial sequences of the Cytochrome b gene showed that parasites were closely related to Haemoproteus iwa reported from frigatebirds in the Pacific Ocean and in the Caribbean. Plasmodium was also detected in a frigatebird on Europa; however, its placement on the phylogenetic tree could not be resolved. We provide strong support for transmission of blood parasites in seabirds in the Western Indian Ocean and suggest that migrations between the Pacific and the Indian oceans could favor the large-scale distribution of Haemoproteus iwa in frigatebird populations.",2014 May 8,"['Bastien, Matthieu', 'Jaeger, Audrey', 'Le Corre, Matthieu', 'Tortosa, Pablo', 'Lebarbenchon, Camille']",PLoS One,,,True
4cd5e0a3e13b16bea2c7e595e6a77344fa3caebc,PMC,Poxviruses in Bats … so What?,http://dx.doi.org/10.3390/v6041564,PMC4014710,24704730,CC BY,"Poxviruses are important pathogens of man and numerous domestic and wild animal species. Cross species (including zoonotic) poxvirus infections can have drastic consequences for the recipient host. Bats are a diverse order of mammals known to carry lethal viral zoonoses such as Rabies, Hendra, Nipah, and SARS. Consequent targeted research is revealing bats to be infected with a rich diversity of novel viruses. Poxviruses were recently identified in bats and the settings in which they were found were dramatically different. Here, we review the natural history of poxviruses in bats and highlight the relationship of the viruses to each other and their context in the Poxviridae family. In addition to considering the zoonotic potential of these viruses, we reflect on the broader implications of these findings. Specifically, the potential to explore and exploit this newfound relationship to study coevolution and cross species transmission together with fundamental aspects of poxvirus host tropism as well as bat virology and immunology.",2014 Apr 3,"['Baker, Kate S.', 'Murcia, Pablo R.']",Viruses,,,True
bab7ccb9c632b7942584edea0ee9bb3c13f86720,PMC,Poxviruses in Bats … so What?,http://dx.doi.org/10.3390/v6041564,PMC4014710,24704730,CC BY,"Poxviruses are important pathogens of man and numerous domestic and wild animal species. Cross species (including zoonotic) poxvirus infections can have drastic consequences for the recipient host. Bats are a diverse order of mammals known to carry lethal viral zoonoses such as Rabies, Hendra, Nipah, and SARS. Consequent targeted research is revealing bats to be infected with a rich diversity of novel viruses. Poxviruses were recently identified in bats and the settings in which they were found were dramatically different. Here, we review the natural history of poxviruses in bats and highlight the relationship of the viruses to each other and their context in the Poxviridae family. In addition to considering the zoonotic potential of these viruses, we reflect on the broader implications of these findings. Specifically, the potential to explore and exploit this newfound relationship to study coevolution and cross species transmission together with fundamental aspects of poxvirus host tropism as well as bat virology and immunology.",2014 Apr 3,"['Baker, Kate S.', 'Murcia, Pablo R.']",Viruses,,,False
033321dcd825a79a8ba380ba3d52d4ea71f45c81,PMC,Analysis of Determinants in Filovirus Glycoproteins Required for Tetherin Antagonism,http://dx.doi.org/10.3390/v6041654,PMC4014715,24721789,CC BY,"The host cell protein tetherin can restrict the release of enveloped viruses from infected cells. The HIV-1 protein Vpu counteracts tetherin by removing it from the site of viral budding, the plasma membrane, and this process depends on specific interactions between the transmembrane domains of Vpu and tetherin. In contrast, the glycoproteins (GPs) of two filoviruses, Ebola and Marburg virus, antagonize tetherin without reducing surface expression, and the domains in GP required for tetherin counteraction are unknown. Here, we show that filovirus GPs depend on the presence of their authentic transmembrane domains for virus-cell fusion and tetherin antagonism. However, conserved residues within the transmembrane domain were dispensable for membrane fusion and tetherin counteraction. Moreover, the insertion of the transmembrane domain into a heterologous viral GP, Lassa virus GPC, was not sufficient to confer tetherin antagonism to the recipient. Finally, mutation of conserved residues within the fusion peptide of Ebola virus GP inhibited virus-cell fusion but did not ablate tetherin counteraction, indicating that the fusion peptide and the ability of GP to drive host cell entry are not required for tetherin counteraction. These results suggest that the transmembrane domains of filoviral GPs contribute to tetherin antagonism but are not the sole determinants.",2014 Apr 9,"['Gnirß, Kerstin', 'Fiedler, Marie', 'Krämer-Kühl, Annika', 'Bolduan, Sebastian', 'Mittler, Eva', 'Becker, Stephan', 'Schindler, Michael', 'Pöhlmann, Stefan']",Viruses,,,True
84aa85f8690419badcdb6d6777763e6fc3235af1,PMC,Arg(972) Insulin receptor substrate-1 is associated with decreased serum angiotensin-converting enzyme 2 levels in acute myocardial infarction patients: in vivo and in vitro evidence,http://dx.doi.org/10.1186/1475-2840-12-151,PMC4015180,24134599,CC BY,"BACKGROUND: Activation of the renin-angiotensin system (RAS) plays a critical role in the pathophysiology of myocardial infarction (MI) and the development of heart failure. Both angiotensin-converting enzyme 2 (ACE2) and insulin/insulin receptor substrate-1 (IRS-1) show cardioprotective effects after acute MI. The Arg(972) IRS-1 polymorphism is associated with diminished activity of insulin. In the present study, we explored the association among Arg(972) IRS-1, acute MI, and serum levels of ACE2. METHODS: A total of 711 subjects, including 351 subjects with first-time acute MI and 360 subjects without a history of MI were genotyped for Arg(972) IRS-1 polymorphism. Serum levels of ACE2 and MI severity scores were determined. Primary human cardiomyocytes with overexpression of wild type IRS-1 or Arg(972) IRS-1 or knockdown of endogenous IRS-1 were exposed to normoxia and hypoxia, and the expression levels of ACE2 were determined. RESULTS: The serum ACE2 level was significantly increased in acute MI patients compared with that of non-MI controls. Compared with wild type IRS-1 carriers, Arg(972) IRS-1 carriers exhibited decreased serum ACE2 levels and increased MI severity scores after MI. Our in vitro data demonstrate that impairment of insulin/IRS-1/PI3K signaling by overexpression of Arg(972)-IRS-1, knockdown of endogenous IRS-1, or PI3K inhibitor can abolish hypoxia-induced IRS-1-associated PI3K activity and ACE2 expression in human cardiomyocytes, which suggests a causal relationship between Arg(972)-IRS-1 and decreased serum ACE2 levels in acute MI patients. Our in vitro data also indicate that insulin/IRS-1/PI3K signaling is required for ACE2 expression in cardiomyocytes, and that hypoxia can enhance the induction effect of insulin/IRS-1/PI3K signaling on ACE2 expression in cardiomyocytes. CONCLUSIONS: This study provides the first evidence of crosstalk between insulin/IRS-1/PI3K signaling and RAS after acute MI, thereby adding fresh insights into the pathophysiology and treatment of acute MI.",2013 Oct 17,"['Liu, Wei', 'Zhou, Xinmin', 'Yu, Fenglei', 'Hu, Jianguo', 'Hu, Wen']",Cardiovasc Diabetol,,,True
206b5371a11c4b903ed2600b579171a3e6873764,PMC,"Prevalence of adenovirus in children with acute respiratory tract infection in Lanzhou, China",http://dx.doi.org/10.1186/1743-422X-10-271,PMC4015357,23984826,CC BY,"BACKGROUND: Human adenovirus (HAdV) is an important agent causing respiratory tract infection in children. Information on the epidemiological and clinical features of HAdV is limited in children with acute respiratory tract infections (ARTIs) in China, especially those of a novel genotype, Ad55. METHODS: In total, 1169 nasopharyngeal aspirates were collected from children younger than 14 years with ARTIs between November 2006 and November 2009. The polymerase chain reaction (PCR) was used to screen HAdVs. All PCR-positive products were sequenced. RESULTS: 74 of 1169 (6.33%) specimens were positive for HAdVs. Among positive cases, AdV3 (58/74) was detected most frequently, followed by AdV11 (10/74), AdV2 (2/74), AdV7 (2/69), AdV6 (1/74), and AdV1 (1/74). AdV55 was found in one case. The incidence of HAdV infection peaked in children aged 3–7 years. The most common clinical diagnosis was upper respiratory infection, and the most common syndrome was fever and cough.The comparison of HAdV and RSV group revealed that Children infected with group AdV were significant older than children infected with group RSV, had more fever but less frequently wheezing, and cough, crackles, and cyanosis, The duration of hospitalization between the AdV group and RSV group was not significant, but a greater frequency of LRTIs was observed in RSV group. CONCLUSIONS: HAdV is an important viral agent in children with ARTIs in Lanzhou City, China. Multiple HAdV serotypes co-circulated with Ad3, which was predominant in this 3-year study. The novel AdV55 genotype was found in one case. No fixed seasonal rhythm could be identified.",2013 Aug 29,"['Jin, Yu', 'Zhang, Rong-fang', 'Xie, Zhi-ping', 'Yan, Kun-long', 'Gao, Han-chun', 'Song, Jing-rong', 'Yuan, Xin-hui', 'Hou, Yun-de', 'Duan, Zhao-jun']",Virol J,,,True
2a7fdc03389aef740cb9d6de762e96e52473b236,PMC,"Viral aetiology influenza like illnesses in Santa Cruz, Bolivia (2010–2012)",http://dx.doi.org/10.1186/1743-422X-11-35,PMC4015617,24564892,CC BY,"BACKGROUND: Acute respiratory infections represent a serious public health issue worldwide but virological aetiologies of Influenza Like Illnesses (ILIs) remain largely unknown in developing countries. This study represents the first attempt to characterise viral aetiologies of ILIs in Bolivia. METHODS: It was performed in Santa Cruz city from January 2010 to September 2012, based on 564 naso-pharyngeal swabs collected in a National Reference Laboratory and real-time PCR techniques, viral cultures and phylogenetic analyses. RESULTS: 50.2% of samples were positive for at least one virus with influenza viruses (Flu A: ~15%; Flu B: ~9%), rhinoviruses (~8%), coronaviruses (~5%) and hRSV (~4%) being the most frequently identified. The pattern of viral infections varied according to age groups. The elucidation rate was the highest (>60%) amongst patients under 10 yo and the lowest (<40%) amongst patients ≥60 yo. Nearly 3% of samples showed dual viral infections. Epidemiological peaks were associated with a predominant virus but generally included 30-50% of infections by different viruses. Unexpectedly, the frequency of influenza in the 0–4 yo population was very low and a complete hRSV eclipse occurred in 2011. Genetic analyses indicated that distinct evolutionary lineages of Flu A(H1N1)pdm2009, Flu A/H3N2 and Flu B have co-circulated in Bolivia in the study period, originating from Central and North America, Europe, Asia and Australia. CONCLUSION: Our results emphasise the requirement for a reinforced epidemiological and genetic follow-up of influenza and other ILIs in Bolivia to further inform the preparation of vaccines used in the region, guide vaccination campaigns and improve the medical management of patients.",2014 Feb 24,"['Delangue, Julie', 'Roca Sanchez, Yelin', 'Piorkowski, Géraldine', 'Bessaud, Maël', 'Baronti, Cécile', 'Thirion-Perrier, Laurence', 'Mafayle, Roxana Loayza', 'Ardaya, Cinthia Avila', 'Aguilera, Gabriela Añez', 'Guzman, Jimmy Revollo', 'Riera, Javier Lora', 'de Lamballerie, Xavier']",Virol J,,,True
7bfcd661fcd1248cb3ecaeea416eee85a689bf32,PMC,Control of HPV-associated tumors by innovative therapeutic HPV DNA vaccine in the absence of CD4+ T cells,http://dx.doi.org/10.1186/2045-3701-4-11,PMC4015858,24594273,CC BY,"Human papillomavirus (HPV) infections are particularly problematic for HIV + and solid organ transplant patients with compromised CD4+ T cell-dependent immunity as they produce more severe and progressive disease compared to healthy individuals. There are no specific treatments for chronic HPV infection, resulting in an urgent unmet need for a modality that is safe and effective for both immunocompromised and otherwise normal patients with recalcitrant disease. DNA vaccination is attractive because it avoids the risks of administration of live vectors to immunocompromised patients, and can induce potent HPV-specific cytotoxic T cell responses. We have developed a DNA vaccine (pNGVL4a-hCRTE6E7L2) encoding calreticulin (CRT) fused to E6, E7 and L2 proteins of HPV-16, the genotype associated with approximately 90% vaginal, vulvar, anal, penile and oropharyngeal HPV-associated cancers and the majority of cervical cancers. Administration of the DNA vaccine by intramuscular (IM) injection followed by electroporation induced significantly greater HPV-specific immune responses compared to IM injection alone or mixed with alum. Furthermore, pNGVL4a-hCRTE6E7L2 DNA vaccination via electroporation of mice carrying an intravaginal HPV-16 E6/E7-expressing syngeneic tumor demonstrated more potent therapeutic effects than IM vaccination alone. Of note, administration of the DNA vaccine by IM injection followed by electroporation elicited potent E6 and E7-specific CD8+ T cell responses and antitumor effects despite CD4+ T cell-depletion, although no antibody response was detected. While CD4+ T cell-depletion did reduce the E6 and E7-specific CD8+ T cell response, it remained sufficient to prevent subcutaneous tumor growth and to eliminate circulating tumor cells in a model of metastatic HPV-16+ cancer. Thus, the antibody response was CD4-dependent, whereas CD4+ T cell help enhanced the E6/E7-specific CD8+ T cell immunity, but was not required. Taken together, our data suggest that pNGVL4a-hCRTE6E7L2 DNA vaccination via electroporation warrants testing in otherwise healthy patients and those with compromised CD4+ T cell immunity to treat HPV-16-associated anogenital disease and cancer.",2014 Mar 4,"['Peng, Shiwen', 'Song, Liwen', 'Knoff, Jayne', 'Wang, Joshua W', 'Chang, Yung-Nien', 'Hannaman, Drew', 'Wu, T-C', 'Alvarez, Ronald D', 'Roden, Richard BS', 'Hung, Chien-Fu']",Cell Biosci,,,True
b3873c777b754d108ce93d5feca0c3dff4a74564,PMC,"A 60-year review on the changing epidemiology of measles in capital Beijing, China, 1951-2011",http://dx.doi.org/10.1186/1471-2458-13-986,PMC4016557,24143899,CC BY,"BACKGROUND: China pledged to join the global effort to eliminate measles by 2012. To improve measles control strategy, the epidemic trend and population immunity of measles were investigated in 1951–2011 in Beijing. METHODS: The changing trend of measles since 1951 was described based on measles surveillance data from Beijing Centre of Disease Control and Prevention (CDC). The measles vaccination coverage and antibody level were assessed by routinely reported measles vaccination data and twenty-one sero-epidemiological surveys. RESULTS: The incidence of measles has decreased significantly from 593.5/100,000 in 1951 (peaked at 2721.0/100,000 in 1955), to 0.5/100,000 in 2011 due to increasing vaccination coverage of 95%-99%. Incidence rebounded from 6.6/100,000 to 24.5/100,000 since 2005 and decreased after measles vaccine (MV) supplementary immunization activities (SIAs) in 2010. Measles antibody positive rate was 85%-95% in most of years since 1981. High-risk districts were spotted in Chaoyang, Fengtai and Changping districts in recent 15 years. Age-specific incidence and proportion of measles varied over time. The most affected population were younger children of 1–4 years before 1978, older children of 5–14 years in 1978–1996, infant of <1 years and adults of ≥15 years in period of aim to measles elimination. CONCLUSION: Strategies at different stages had a prevailing effect on the epidemic dynamics of measles in recent 60 years in Beijing. It will be essential to validate reported vaccination coverage, improve vaccination coverage in adults and strengthen measles surveillance in the anticipated elimination campaign for measles.",2013 Oct 21,"['Li, Juan', 'Lu, Li', 'Pang, Xinghuo', 'Sun, Meiping', 'Ma, Rui', 'Liu, Donglei', 'Wu, Jiang']",BMC Public Health,,,True
519b82201745afd08726b2c3e87cad65f8409da5,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,True
93c503c5143a7b949665b91e735de908fb437410,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
f8f3b36606fcb6e4275eba987085c94389b6f36e,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
89dc7cd98b98836a8fed26eb42813ef9c8741cb2,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
9091a42a55fd924dbe8273cfdcec30c14e7bb52b,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
8654df96fb9cd8ae9dc157fd4bdbf918760de8a1,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
5374c4e483eccc3bd651bd9391a4a8866654445d,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
5a783fbb41a3064e1bc6e06f18f5a126db1b7e44,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
ec814d30f47d6fe554f3fb65a9813e7028b51b6f,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
249496d6fe8f7583d9614407315177b5b634a6b3,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
95484e01993954fba67480d038aea0558c32573c,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
f6779c3cfe1534b21e84f04a454294add1f755e9,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
e9879104d64146559cc35fdeb001c7c0ea608d2d,PMC,Molecular Evolution of the Primate α-/θ-Defensin Multigene Family,http://dx.doi.org/10.1371/journal.pone.0097425,PMC4018336,24819937,CC BY,"The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.",2014 May 12,"['Cheng, Dong-Qiang', 'Li, Ying', 'Huang, Jing-Fei']",PLoS One,,,False
4930fc9d9e3cb5bea0a97320187aca766f07493d,PMC,Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus,http://dx.doi.org/10.1186/1743-422X-11-82,PMC4018502,24885320,CC BY,"BACKGROUND: Public health risks associated to infection by human coronaviruses remain considerable and vaccination is a key option for preventing the resurgence of severe acute respiratory syndrome coronavirus (SARS-CoV). We have previously reported that antibodies elicited by a SARS-CoV vaccine candidate based on recombinant, full-length SARS-CoV Spike-protein trimers, trigger infection of immune cell lines. These observations prompted us to investigate the molecular mechanisms and responses to antibody-mediated infection in human macrophages. METHODS: We have used primary human immune cells to evaluate their susceptibility to infection by SARS-CoV in the presence of anti-Spike antibodies. Fluorescence microscopy and real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) were utilized to assess occurrence and consequences of infection. To gain insight into the underlying molecular mechanism, we performed mutational analysis with a series of truncated and chimeric constructs of fragment crystallizable γ receptors (FcγR), which bind antibody-coated pathogens. RESULTS: We show here that anti-Spike immune serum increased infection of human monocyte-derived macrophages by replication-competent SARS-CoV as well as Spike-pseudotyped lentiviral particles (SARS-CoVpp). Macrophages infected with SARS-CoV, however, did not support productive replication of the virus. Purified anti-viral IgGs, but not other soluble factor(s) from heat-inactivated mouse immune serum, were sufficient to enhance infection. Antibody-mediated infection was dependent on signaling-competent members of the human FcγRII family, which were shown to confer susceptibility to otherwise naïve ST486 cells, as binding of immune complexes to cell surface FcγRII was necessary but not sufficient to trigger antibody-dependent enhancement (ADE) of infection. Furthermore, only FcγRII with intact cytoplasmic signaling domains were competent to sustain ADE of SARS-CoVpp infection, thus providing additional information on the role of downstream signaling by FcγRII. CONCLUSIONS: These results demonstrate that human macrophages can be infected by SARS-CoV as a result of IgG-mediated ADE and indicate that this infection route requires signaling pathways activated downstream of binding to FcγRII receptors.",2014 May 6,"['Yip, Ming Shum', 'Leung, Nancy Hiu Lan', 'Cheung, Chung Yan', 'Li, Ping Hung', 'Lee, Horace Hok Yeung', 'Daëron, Marc', 'Peiris, Joseph Sriyal Malik', 'Bruzzone, Roberto', 'Jaume, Martial']",Virol J,,,True
b40b2c7a9a57323d18e7b564d0dec8ee330d3d01,PMC,Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1,http://dx.doi.org/10.7554/eLife.02362,PMC4018625,24843023,CC BY,"BST2/tetherin, an antiviral restriction factor, inhibits the release of enveloped viruses from the cell surface. Human immunodeficiency virus-1 (HIV-1) antagonizes BST2 through viral protein u (Vpu), which downregulates BST2 from the cell surface. We report the crystal structure of a protein complex containing Vpu and BST2 cytoplasmic domains and the core of the clathrin adaptor protein complex 1 (AP1). This, together with our biochemical and functional validations, reveals how Vpu hijacks the AP1-dependent membrane trafficking pathways to mistraffick BST2. Vpu mimics a canonical acidic dileucine-sorting motif to bind AP1 in the cytosol, while simultaneously interacting with BST2 in the membrane. These interactions enable Vpu to build on an intrinsic interaction between BST2 and AP1, presumably causing the observed retention of BST2 in juxtanuclear endosomes and stimulating its degradation in lysosomes. The ability of Vpu to hijack AP-dependent trafficking pathways suggests a potential common theme for Vpu-mediated downregulation of host proteins. DOI: http://dx.doi.org/10.7554/eLife.02362.001",2014 Apr 29,"['Jia, Xiaofei', 'Weber, Erin', 'Tokarev, Andrey', 'Lewinski, Mary', 'Rizk, Maryan', 'Suarez, Marissa', 'Guatelli, John', 'Xiong, Yong']",eLife,,,True
1b2d0c795271b2dffeba58396e52cca462185d78,PMC,Communicating and Monitoring Surveillance and Response Activities for Malaria Elimination: China's “1-3-7” Strategy,http://dx.doi.org/10.1371/journal.pmed.1001642,PMC4019513,24824170,CC BY,"Qi Gao and colleagues describe China's 1-3-7 strategy for eliminating malaria: reporting of malaria cases within one day, their confirmation and investigation within three days, and the appropriate public health response to prevent further transmission within seven days.",2014 May 13,"['Cao, Jun', 'Sturrock, Hugh J. W.', 'Cotter, Chris', 'Zhou, Shuisen', 'Zhou, Huayun', 'Liu, Yaobao', 'Tang, Linhua', 'Gosling, Roly D.', 'Feachem, Richard G. A.', 'Gao, Qi']",PLoS Med,,,True
1ab0742b23affe5d2f9a5adc6b98e3f89defd930,PMC,Usefulness of Cellular Analysis of Bronchoalveolar Lavage Fluid for Predicting the Etiology of Pneumonia in Critically Ill Patients,http://dx.doi.org/10.1371/journal.pone.0097346,PMC4019586,24824328,CC BY,"BACKGROUND: The usefulness of bronchoalveolar lavage (BAL) fluid cellular analysis in pneumonia has not been adequately evaluated. This study investigated the ability of cellular analysis of BAL fluid to differentially diagnose bacterial pneumonia from viral pneumonia in adult patients who are admitted to intensive care unit. METHODS: BAL fluid cellular analysis was evaluated in 47 adult patients who underwent bronchoscopic BAL following less than 24 hours of antimicrobial agent exposure. The abilities of BAL fluid total white blood cell (WBC) counts and differential cell counts to differentiate between bacterial and viral pneumonia were evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Bacterial pneumonia (n = 24) and viral pneumonia (n = 23) were frequently associated with neutrophilic pleocytosis in BAL fluid. BAL fluid median total WBC count (2,815/µL vs. 300/µL, P<0.001) and percentage of neutrophils (80.5% vs. 54.0%, P = 0.02) were significantly higher in the bacterial pneumonia group than in the viral pneumonia group. In ROC curve analysis, BAL fluid total WBC count showed the best discrimination, with an area under the curve of 0.855 (95% CI, 0.750–0.960). BAL fluid total WBC count ≥510/µL had a sensitivity of 83.3%, specificity of 78.3%, positive likelihood ratio (PLR) of 3.83, and negative likelihood ratio (NLR) of 0.21. When analyzed in combination with serum procalcitonin or C-reactive protein, sensitivity was 95.8%, specificity was 95.7%, PLR was 8.63, and NLR was 0.07. BAL fluid total WBC count ≥510/µL was an independent predictor of bacterial pneumonia with an adjusted odds ratio of 13.5 in multiple logistic regression analysis. CONCLUSIONS: Cellular analysis of BAL fluid can aid early differential diagnosis of bacterial pneumonia from viral pneumonia in critically ill patients.",2014 May 13,"['Choi, Sang-Ho', 'Hong, Sang-Bum', 'Hong, Hyo-Lim', 'Kim, Sung-Han', 'Huh, Jin Won', 'Sung, Heungsup', 'Lee, Sang-Oh', 'Kim, Mi-Na', 'Jeong, Jin-Yong', 'Lim, Chae-Man', 'Kim, Yang Soo', 'Woo, Jun Hee', 'Koh, Younsuck']",PLoS One,,,True
1f1c43d3f7a43ad4a16b8ded2b2ac384f3db3b4c,PMC,It is Unlikely That Influenza Viruses Will Cause a Pandemic Again Like What Happened in 1918 and 1919,http://dx.doi.org/10.3389/fpubh.2014.00039,PMC4019839,24847476,CC BY,,2014 May 7,"Song, Liting",Front Public Health,,,True
540a2a909e0ae17de908c236742379d073ab2d95,PMC,Evaluation of Three Automated Nucleic Acid Extraction Systems for Identification of Respiratory Viruses in Clinical Specimens by Multiplex Real-Time PCR,http://dx.doi.org/10.1155/2014/430650,PMC4020539,24868527,CC BY,"A total of 84 nasopharyngeal swab specimens were collected from 84 patients. Viral nucleic acid was extracted by three automated extraction systems: QIAcube (Qiagen, Germany), EZ1 Advanced XL (Qiagen), and MICROLAB Nimbus IVD (Hamilton, USA). Fourteen RNA viruses and two DNA viruses were detected using the Anyplex II RV16 Detection kit (Seegene, Republic of Korea). The EZ1 Advanced XL system demonstrated the best analytical sensitivity for all the three viral strains. The nucleic acids extracted by EZ1 Advanced XL showed higher positive rates for virus detection than the others. Meanwhile, the MICROLAB Nimbus IVD system was comprised of fully automated steps from nucleic extraction to PCR setup function that could reduce human errors. For the nucleic acids recovered from nasopharyngeal swab specimens, the QIAcube system showed the fewest false negative results and the best concordance rate, and it may be more suitable for detecting various viruses including RNA and DNA virus strains. Each system showed different sensitivity and specificity for detection of certain viral pathogens and demonstrated different characteristics such as turnaround time and sample capacity. Therefore, these factors should be considered when new nucleic acid extraction systems are introduced to the laboratory.",2014 Apr 28,"['Kim, Yoonjung', 'Han, Mi-Soon', 'Kim, Juwon', 'Kwon, Aerin', 'Lee, Kyung-A']",Biomed Res Int,,,True
b7f783ce7fc3715b718384a9295bd8afb24b93ec,PMC,"Respiratory viruses associated with patients older than 50 years presenting with ILI in Senegal, 2009 to 2011",http://dx.doi.org/10.1186/1471-2334-14-189,PMC4020602,24712515,CC BY,"BACKGROUND: In Africa, especially in West Africa, studies about the prevalence and diversity of respiratory viruses (influenza and others) in elderly people are largely lacking. In studies done elsewhere, it is well established that older people, when compared with younger adults, are at greater risk of significant morbidity and mortality from complications arising from influenza. The main aim of this study was to determine the prevalence and the diversity of respiratory viruses associated with ILI cases in adults over 50 years old in Senegal. METHODS: The recruitment period of this study was from January 2009 to December 2011. 232 patients aged 50 years and above presenting ILI cases were enrolled. Nasal-pharyngeal and/or oral pharyngeal swabs were collected from patients. RNA was extracted from 200 μl of each sample followed by a two-step real-time RT-PCR. The Anyplex™ II RV16 Detection kit was used for viral detection. The kit enabled the simultaneous detection of the presence of 16 respiratory viruses. RESULTS: 150 viruses were detected: influenza viruses (44.7%) and rhinoviruses (26.7%) were the most prevalent. We detected 13 human parainfluenza viruses (8.7%), 7 human respiratory syncytial viruses (4.7%), 6 coronaviruses (4%), 5 human metapneumoviruses (3.3%), 5 human adenoviruses (3.3%) and 1 human bocavirus (0.7%). 14 cases (6%) of dual virus infections and one triple viral detection case were encountered. 56 (56.6%) viruses detected were found in the 50-64 year old age group, 59 (76.6%; P < 0.001) from 65–74 year old age group and 35 (62.5%) were detected in the ≥75 year old age group. The viral co-infections were more frequent in the 65-74 age group (9/15). CONCLUSIONS: This pilot study demonstrates a variety of respiratory viruses in the elderly. It also highlights a high prevalence of these viruses in this age group. We speculate from these results that the impact of respiratory viruses other than influenza on the elderly has been considerably underestimated. A more exhaustive study seems necessary in order to provide a more complete picture of the burden of respiratory viruses on morbidity among adults over 50 years old in the sub-Saharan context.",2014 Apr 8,"['Dia, Ndongo', 'Richard, Vincent', 'Kiori, Davy', 'Cisse, El Hadj Abdoul Khadir', 'Sarr, Fatoumata Diène', 'Faye, Abdourahmane', 'Goudiaby, Déborah G', 'Diop, Ousmane M', 'Niang, Mbayame N']",BMC Infect Dis,,,True
a27702025191a260051091b84a0d5c9b68829440,PMC,"The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus",http://dx.doi.org/10.1371/journal.pone.0096579,PMC4020762,24827144,CC BY,"Type I interferons (IFN-α and β) induce dynamic host defense mechanisms to inhibit viral infections. It has been recently recognized that the interferon-inducible transmembrane proteins (IFITM) 1, 2 and 3 can block entry of a broad spectrum of RNA viruses. However, no study to date has focused on the role of IFITM proteins in DNA virus restriction. Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. However, IFITM1, 2 and 3 overexpression did not inhibit HPV16 infection; rather, IFITM1 and IFITM3 modestly enhanced HPV16 infection in various cell types including primary keratinocytes. Moreover, IFITM1, 2 and 3 did not inhibit infection by two other DNA viruses, human cytomegalovirus (HCMV) and adenovirus type 5 (Ad5). Taken together, we reveal that the entry of several DNA viruses, including HPV, HCMV, and Ad5 is not affected by IFITM1, 2 and 3 expression. These results imply that HPV, and other DNA viruses, may bypass IFITM restriction during intracellular trafficking.",2014 May 14,"['Warren, Cody J.', 'Griffin, Laura M.', 'Little, Alexander S.', 'Huang, I-Chueh', 'Farzan, Michael', 'Pyeon, Dohun']",PLoS One,,,True
866fb412a1ef52e7696d7a50400760ad00b0db9f,PMC,"The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus",http://dx.doi.org/10.1371/journal.pone.0096579,PMC4020762,24827144,CC BY,"Type I interferons (IFN-α and β) induce dynamic host defense mechanisms to inhibit viral infections. It has been recently recognized that the interferon-inducible transmembrane proteins (IFITM) 1, 2 and 3 can block entry of a broad spectrum of RNA viruses. However, no study to date has focused on the role of IFITM proteins in DNA virus restriction. Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. However, IFITM1, 2 and 3 overexpression did not inhibit HPV16 infection; rather, IFITM1 and IFITM3 modestly enhanced HPV16 infection in various cell types including primary keratinocytes. Moreover, IFITM1, 2 and 3 did not inhibit infection by two other DNA viruses, human cytomegalovirus (HCMV) and adenovirus type 5 (Ad5). Taken together, we reveal that the entry of several DNA viruses, including HPV, HCMV, and Ad5 is not affected by IFITM1, 2 and 3 expression. These results imply that HPV, and other DNA viruses, may bypass IFITM restriction during intracellular trafficking.",2014 May 14,"['Warren, Cody J.', 'Griffin, Laura M.', 'Little, Alexander S.', 'Huang, I-Chueh', 'Farzan, Michael', 'Pyeon, Dohun']",PLoS One,,,False
fb9b75c5e290a5ff3b49c2f0f93e05a1dcff78df,PMC,Tollip or Not Tollip: What Are the Evolving Questions behind It?,http://dx.doi.org/10.1371/journal.pone.0097219,PMC4020778,24828816,CC BY,"Tollip plays an important role in the interleukin-1 receptor IL-1R and Toll pathways. As a modulator of the immune pathway, it indirectly controls the amount of antimicrobial peptides. This could indicate a vital step in maintaining animal immune systems and preventing infection. Evolutionary questions are crucial to understanding the conservation and functioning of the biochemical pathways like the Tollip-mediated one. Through an analysis of 36 sequences of the Tollip protein from different animal taxa, downloaded from Kyoto Encyclopedia of Genes and Genomes (KEGG) databank, we inferred diverse evolutionary parameters, such as molecular selection and structure conservation, by analyzing residue by residue, beyond the canonical parameters to this type of study, as maximum likelihood trees. We found that Tollip presented different trends in its evolving history. In primates, the protein is becoming more unstable, just the opposite is observed in the arthropod group. The most interesting finding was the concentration of positively selected residues at amino terminal ends. Some observed topological incongruences in maximum likelihood trees of complete and curated Tollip data sets could be explained through horizontal transfers, evidenced by recombination detection. These results suggest that there is more to be researched and understood about this protein.",2014 May 14,"['Luiz, Denis Prudencio', 'Santos Júnior, Célio Dias', 'Bonetti, Ana Maria', 'Brandeburgo, Malcom Antônio Manfredi']",PLoS One,,,True
d65ef4b00759d797d28454625b4de2814675bb56,PMC,Interferon-induced HERC5 is evolving under positive selection and inhibits HIV-1 particle production by a novel mechanism targeting Rev/RRE-dependent RNA nuclear export,http://dx.doi.org/10.1186/1742-4690-11-27,PMC4021598,24693865,CC BY,"BACKGROUND: Type I interferon (IFN) inhibits virus replication by activating multiple antiviral mechanisms and pathways. It has long been recognized that type I IFNs can potently block HIV-1 replication in vitro; as such, HIV-1 has been used as a system to identify and characterize IFN-induced antiviral proteins responsible for this block. IFN-induced HERC5 contains an amino-terminal Regulator of Chromosome Condensation 1 (RCC1)-like domain and a carboxyl-terminal Homologous to the E6-AP Carboxyl Terminus (HECT) domain. HERC5 is the main cellular E3 ligase that conjugates the IFN-induced protein ISG15 to proteins. This E3 ligase activity was previously shown to inhibit the replication of evolutionarily diverse viruses, including HIV-1. The contribution of the RCC1-like domain to the antiviral activity of HERC5 was previously unknown. RESULTS: In this study, we showed that HERC5 inhibits HIV-1 particle production by a second distinct mechanism that targets the nuclear export of Rev/RRE-dependent RNA. Unexpectedly, the E3 ligase activity of HERC5 was not required for this inhibition. Instead, this activity required the amino-terminal RCC1-like domain of HERC5. Inhibition correlated with a reduction in intracellular RanGTP protein levels and/or the ability of RanGTP to interact with RanBP1. Inhibition also correlated with altered subcellular localization of HIV-1 Rev. In addition, we demonstrated that positive evolutionary selection is operating on HERC5. We identified a region in the RCC1-like domain that exhibits an exceptionally high probability of having evolved under positive selection and showed that this region is required for HERC5-mediated inhibition of nuclear export. CONCLUSIONS: We have identified a second distinct mechanism by which HERC5 inhibits HIV-1 replication and demonstrate that HERC5 is evolving under strong positive selection. Together, our findings contribute to a growing body of evidence suggesting that HERC5 is a novel host restriction factor.",2014 Apr 3,"['Woods, Matthew William', 'Tong, Jessica Gayle', 'Tom, Sean Kevin', 'Szabo, Peter Anthony', 'Cavanagh, Peter Craig', 'Dikeakos, Jimmy Dimitrios', 'Haeryfar, SM Mansour', 'Barr, Stephen Dominic']",Retrovirology,,,True
d20b60ebfc43e34474624c454c84afb31ddec20c,PMC,Interferon-induced HERC5 is evolving under positive selection and inhibits HIV-1 particle production by a novel mechanism targeting Rev/RRE-dependent RNA nuclear export,http://dx.doi.org/10.1186/1742-4690-11-27,PMC4021598,24693865,CC BY,"BACKGROUND: Type I interferon (IFN) inhibits virus replication by activating multiple antiviral mechanisms and pathways. It has long been recognized that type I IFNs can potently block HIV-1 replication in vitro; as such, HIV-1 has been used as a system to identify and characterize IFN-induced antiviral proteins responsible for this block. IFN-induced HERC5 contains an amino-terminal Regulator of Chromosome Condensation 1 (RCC1)-like domain and a carboxyl-terminal Homologous to the E6-AP Carboxyl Terminus (HECT) domain. HERC5 is the main cellular E3 ligase that conjugates the IFN-induced protein ISG15 to proteins. This E3 ligase activity was previously shown to inhibit the replication of evolutionarily diverse viruses, including HIV-1. The contribution of the RCC1-like domain to the antiviral activity of HERC5 was previously unknown. RESULTS: In this study, we showed that HERC5 inhibits HIV-1 particle production by a second distinct mechanism that targets the nuclear export of Rev/RRE-dependent RNA. Unexpectedly, the E3 ligase activity of HERC5 was not required for this inhibition. Instead, this activity required the amino-terminal RCC1-like domain of HERC5. Inhibition correlated with a reduction in intracellular RanGTP protein levels and/or the ability of RanGTP to interact with RanBP1. Inhibition also correlated with altered subcellular localization of HIV-1 Rev. In addition, we demonstrated that positive evolutionary selection is operating on HERC5. We identified a region in the RCC1-like domain that exhibits an exceptionally high probability of having evolved under positive selection and showed that this region is required for HERC5-mediated inhibition of nuclear export. CONCLUSIONS: We have identified a second distinct mechanism by which HERC5 inhibits HIV-1 replication and demonstrate that HERC5 is evolving under strong positive selection. Together, our findings contribute to a growing body of evidence suggesting that HERC5 is a novel host restriction factor.",2014 Apr 3,"['Woods, Matthew William', 'Tong, Jessica Gayle', 'Tom, Sean Kevin', 'Szabo, Peter Anthony', 'Cavanagh, Peter Craig', 'Dikeakos, Jimmy Dimitrios', 'Haeryfar, SM Mansour', 'Barr, Stephen Dominic']",Retrovirology,,,False
7967040b2131b69fec61d9f1d5c14dd214c49989,PMC,A look at the ASEAN-NDI: building a regional health R&D innovation network,http://dx.doi.org/10.1186/2049-9957-3-15,PMC4021759,24834349,CC BY,"Globally, there are growing efforts to address diseases through the advancement in health research and development (R&D), strengthening of regional cooperation in science and technology (particularly on product discovery and development), and implementation of the World Health Assembly Resolution 61.21 (WHA61.21) on the Global Strategy and Plan of Action on Public Health, Innovation, and Intellectual Property (GSPA-PHI). As such, the Association of Southeast Asian Nations (ASEAN) is responding to this through the establishment of the ASEAN-Network for Drugs, Diagnostics, Vaccines, and Traditional Medicines Innovation (ASEAN-NDI). This is important in the ASEAN considering that infectious tropical diseases remain prevalent, emerging, and reemerging in the region. This paper looks into the evolution of the ASEAN-NDI from its inception in 2009, to how it is at present, and its plans to mitigate public health problems regionally and even globally.",2014 Apr 28,"['Montoya, Jaime C', 'Rebulanan, Carina L', 'Parungao, Nico Angelo C', 'Ramirez, Bernadette']",Infect Dis Poverty,,,True
39c02a3753a3488525c47e79c1f0eddf16195ebb,PMC,A look at the ASEAN-NDI: building a regional health R&D innovation network,http://dx.doi.org/10.1186/2049-9957-3-15,PMC4021759,24834349,CC BY,"Globally, there are growing efforts to address diseases through the advancement in health research and development (R&D), strengthening of regional cooperation in science and technology (particularly on product discovery and development), and implementation of the World Health Assembly Resolution 61.21 (WHA61.21) on the Global Strategy and Plan of Action on Public Health, Innovation, and Intellectual Property (GSPA-PHI). As such, the Association of Southeast Asian Nations (ASEAN) is responding to this through the establishment of the ASEAN-Network for Drugs, Diagnostics, Vaccines, and Traditional Medicines Innovation (ASEAN-NDI). This is important in the ASEAN considering that infectious tropical diseases remain prevalent, emerging, and reemerging in the region. This paper looks into the evolution of the ASEAN-NDI from its inception in 2009, to how it is at present, and its plans to mitigate public health problems regionally and even globally.",2014 Apr 28,"['Montoya, Jaime C', 'Rebulanan, Carina L', 'Parungao, Nico Angelo C', 'Ramirez, Bernadette']",Infect Dis Poverty,,,False
2f4ea657c6c2e9ee90b6ef1af40e2626e5bb488b,PMC,Potential Sources and Roles of Adaptive Immunity in Age-Related Macular Degeneration: Shall We Rename AMD into Autoimmune Macular Disease?,http://dx.doi.org/10.1155/2014/532487,PMC4022009,24876950,CC BY,"Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly throughout the industrialized world. Its most prominent pathologic features are lesions involving the retinal pigment epithelium (RPE) the Bruch's membrane, the degeneration of photoreceptors, and, in the most aggressive cases, choroidal neovascularization. Genetic associations between the risk of developing AMD and polymorphism within components of the complement system, as well as chemokine receptors expressed on microglial cells and macrophages, have linked retinal degeneration and choroidal neovascularization to innate immunity (inflammation). In addition to inflammation, players of the adaptive immunity including cytokines, chemokines, antibodies, and T cells have been detected in animal models of AMD and in patients suffering from this pathology. These observations suggest that adaptive immunity might play a role in different processes associated with AMD such as RPE atrophy, neovascularization, and retinal degeneration. To this date however, the exact roles (if any) of autoantibodies and T cells in AMD remain unknown. In this review we discuss the potential effects of adaptive immune responses in AMD pathogenesis.",2014 Apr 30,"Camelo, Serge",Autoimmune Dis,,,True
6e4a162ab67f96a6b889e1f09d5531770fb1996d,PMC,An RNA Aptamer That Specifically Binds to the Glycosylated Hemagglutinin of Avian Influenza Virus and Suppresses Viral Infection in Cells,http://dx.doi.org/10.1371/journal.pone.0097574,PMC4023947,24835440,CC BY,"The influenza virus surface glycoprotein hemagglutinin (HA) is responsible for viral attachment to sialic acid-containing host cell receptors and it facilitates the initial stage of viral infection. In the present study, we isolated an RNA aptamer specific to the glycosylated receptor-binding domain of the HA protein (gHA1) after 12 cycles of the systematic evolution of ligands by exponential enrichment procedure (SELEX), and we then investigated if the selected aptamer suppresses viral infection in host cells. Nitrocellulose filter binding and enzyme-linked immunosorbent assay (ELISA) experiments revealed that 1 RNA aptamer, HA12-16, bound specifically to the gHA1 protein. Cell viability assay showed that the HA12-16 RNA aptamer suppressed viral infection in host cells by enhancing cell viability. Immunofluorescence microscopic analysis further demonstrated that the HA12-16 RNA aptamer suppresses viral attachment to host cells by neutralizing the receptor-binding site of influenza virus HA. These results indicate that the isolated RNA aptamer can be developed as an antiviral reagent against influenza through appropriate therapeutic formulation.",2014 May 16,"['Kwon, Hyun-Mi', 'Lee, Kwang Hyun', 'Han, Byung Woo', 'Han, Mi Ra', 'Kim, Dong Ho', 'Kim, Dong-Eun']",PLoS One,,,True
c40606c62e96d3ea8313b67bf60e8148eeb45f05,PMC,After 2015: infectious diseases in a new era of health and development,http://dx.doi.org/10.1098/rstb.2013.0426,PMC4024220,24821913,CC BY,"Running over timescales that span decades or centuries, the epidemiological transition provides the central narrative of global health. In this transition, a reduction in mortality is followed by a reduction in fertility, creating larger, older populations in which the main causes of illness and death are no longer acute infections of children but chronic diseases of adults. Since the year 2000, the Millennium Development Goals (MDGs) have provided a framework for accelerating the decline of infectious diseases, backed by a massive injection of foreign investment to low-income countries. Despite the successes of the MDGs era, the inhabitants of low-income countries still suffer an enormous burden of disease owing to diarrhoea, pneumonia, HIV/AIDS, tuberculosis, malaria and other pathogens. Adding to the predictable burden of endemic disease, the threat of pandemics is ever-present and global. With a view to the future, this review spotlights five aspects of the fight against infection beyond 2015, when the MDGs will be replaced by a new set of goals for poverty reduction and sustainable development. These aspects are: exploiting the biological links between infectious and non-infectious diseases; controlling infections among the new urban majority; enhancing the response to international health threats; expanding childhood immunization programmes to prevent acute and chronic diseases in adults; and working towards universal health coverage. By scanning the wider horizon now, infectious disease specialists have the chance to shape the post-2015 era of health and development.",2014 Jun 19,"Dye, Christopher",Philos Trans R Soc Lond B Biol Sci,,,True
ecb3c8e94fb9e56b8ca7f05687f791f3db024a94,PMC,Social mixing patterns in rural and urban areas of southern China,http://dx.doi.org/10.1098/rspb.2014.0268,PMC4024290,24789897,CC BY,"A dense population, global connectivity and frequent human–animal interaction give southern China an important role in the spread and emergence of infectious disease. However, patterns of person-to-person contact relevant to the spread of directly transmitted infections such as influenza remain poorly quantified in the region. We conducted a household-based survey of travel and contact patterns among urban and rural populations of Guangdong, China. We measured the character and distance from home of social encounters made by 1821 individuals. Most individuals reported 5–10 h of contact with around 10 individuals each day; however, both distributions have long tails. The distribution of distance from home at which contacts were made is similar: most were within a kilometre of the participant's home, while some occurred further than 500 km away. Compared with younger individuals, older individuals made fewer contacts which tended to be closer to home. There was strong assortativity in age-based contact rates. We found no difference between the total number or duration of contacts between urban and rural participants, but urban participants tended to make contacts closer to home. These results can improve mathematical models of infectious disease emergence, spread and control in southern China and throughout the region.",2014 Jun 22,"['Read, Jonathan M.', 'Lessler, Justin', 'Riley, Steven', 'Wang, Shuying', 'Tan, Li Jiu', 'Kwok, Kin On', 'Guan, Yi', 'Jiang, Chao Qiang', 'Cummings, Derek A. T.']",Proc Biol Sci,,,True
15dddee0b99b7095553fde91f32e7ae83c15e9ef,PMC,European Monitoring Systems and Data for Assessing Environmental and Climate Impacts on Human Infectious Diseases,http://dx.doi.org/10.3390/ijerph110403894,PMC4025019,24722542,CC BY,"Surveillance is critical to understanding the epidemiology and control of infectious diseases. The growing concern over climate and other drivers that may increase infectious disease threats to future generations has stimulated a review of the surveillance systems and environmental data sources that might be used to assess future health impacts from climate change in Europe. We present an overview of organizations, agencies and institutions that are responsible for infectious disease surveillance in Europe. We describe the surveillance systems, tracking tools, communication channels, information exchange and outputs in light of environmental and climatic drivers of infectious diseases. We discuss environmental and climatic data sets that lend themselves to epidemiological analysis. Many of the environmental data sets have a relatively uniform quality across EU Member States because they are based on satellite measurements or EU funded FP6 or FP7 projects with full EU coverage. Case-reporting systems for surveillance of infectious diseases should include clear and consistent case definitions and reporting formats that are geo-located at an appropriate resolution. This will allow linkage to environmental, social and climatic sources that will enable risk assessments, future threat evaluations, outbreak management and interventions to reduce disease burden.",2014 Apr 9,"['Nichols, Gordon L.', 'Andersson, Yvonne', 'Lindgren, Elisabet', 'Devaux, Isabelle', 'Semenza, Jan C.']",Int J Environ Res Public Health,,,True
35d7e6d1717c9b8604c8370ffdf26ea9569aa75d,PMC,Influenza A Virus Encoding Secreted Gaussia Luciferase as Useful Tool to Analyze Viral Replication and Its Inhibition by Antiviral Compounds and Cellular Proteins,http://dx.doi.org/10.1371/journal.pone.0097695,PMC4026478,24842154,CC BY,"Reporter genes inserted into viral genomes enable the easy and rapid quantification of virus replication, which is instrumental to efficient in vitro screening of antiviral compounds or in vivo analysis of viral spread and pathogenesis. Based on a published design, we have generated several replication competent influenza A viruses carrying either fluorescent proteins or Gaussia luciferase. Reporter activity could be readily quantified in infected cultures, but the virus encoding Gaussia luciferase was more stable than viruses bearing fluorescent proteins and was therefore analyzed in detail. Quantification of Gaussia luciferase activity in the supernatants of infected culture allowed the convenient and highly sensitive detection of viral spread, and enzymatic activity correlated with the number of infectious particles released from infected cells. Furthermore, the Gaussia luciferase encoding virus allowed the sensitive quantification of the antiviral activity of the neuraminidase inhibitor (NAI) zanamivir and the host cell interferon-inducible transmembrane (IFITM) proteins 1–3, which are known to inhibit influenza virus entry. Finally, the virus was used to demonstrate that influenza A virus infection is sensitive to a modulator of endosomal cholesterol, in keeping with the concept that IFITMs inhibit viral entry by altering cholesterol levels in the endosomal membrane. In sum, we report the characterization of a novel influenza A reporter virus, which allows fast and sensitive detection of viral spread and its inhibition, and we show that influenza A virus entry is sensitive to alterations of endosomal cholesterol levels.",2014 May 19,"['Eckert, Nadine', 'Wrensch, Florian', 'Gärtner, Sabine', 'Palanisamy, Navaneethan', 'Goedecke, Ulrike', 'Jäger, Nils', 'Pöhlmann, Stefan', 'Winkler, Michael']",PLoS One,,,True
6081206484e5e671f9a73195a8b1fac39e456a3e,PMC,Ethical Alternatives to Experiments with Novel Potential Pandemic Pathogens,http://dx.doi.org/10.1371/journal.pmed.1001646,PMC4028196,24844931,CC BY,Please see later in the article for the Editors' Summary,2014 May 20,"['Lipsitch, Marc', 'Galvani, Alison P.']",PLoS Med,,,True
a80b756097aea945ba90510f7fa55cc84f849686,PMC,Effect of Chicken Egg Yolk Antibodies (IgY) against Diarrhea in Domesticated Animals: A Systematic Review and Meta-Analysis,http://dx.doi.org/10.1371/journal.pone.0097716,PMC4028221,24846286,CC BY,"BACKGROUND: IgY antibodies are serum immunoglobulin in birds, reptiles and amphibians, and are transferred from serum to egg yolk to confer passive immunity to their embryos and offspring. Currently, the oral passive immunization using chicken IgY has been focused as an alternative to antibiotics for the treatment and control of diarrhea in animals and humans. This systematic review was focused to determine the effect of IgY in controlling and preventing diarrhea in domesticated animals including Piglets, Mice, Poultry and Calves. METHODS AND RESULTS: Previous research reports focused on treatment effect of Chicken IgY against diarrhea were retrieved from different electronic data bases (MEDLINE, EMBASE, SPRINGER-LINK, WILEY, AGRICOLA, MEDWELL Journals, Scientific Publish, Chinese articles from Core periodicals in 2012). A total of 61 studies in 4 different animal classes met the inclusion criteria. Data on study characteristics and outcome measures were extracted. The pooled relative risk (RR) of 49 studies of different animals [Piglets – 22; Mice – 14; Poultry – 7 and Calves – 6] in meta-analyses revealed that, IgY significantly reduced the risk of diarrhea in treatment group when compare to the placebo. However, the 95% confidence intervals of the majority of studies in animal class piglets and calves embrace RR of one. The same results were obtained in sub group analyses (treatment regiment – prophylactic or therapeutic; pathogen type – bacterial or viral). Perhaps, this inconsistency in the effect of IgY at the individual study level and overall effect measures could be influenced by the methodological heterogeneity. CONCLUSION: The present systematic review (SR) and meta-analysis demonstrated the beneficial effect of IgY. This supports the opinion that IgY is useful for prophylaxis and treatment. However, more intensive studies using the gold standard animal experiments with the focus to use IgY alone or in combination with other alternative strategies are indispensable.",2014 May 20,"['Diraviyam, Thirumalai', 'Zhao, Bin', 'Wang, Yuan', 'Schade, Ruediger', 'Michael, Antonysamy', 'Zhang, Xiaoying']",PLoS One,,,True
d31c8c30c1aaad525d6a1714296376a091414e5e,PMC,Trends in influenza vaccination coverage in Portugal from 1998 to 2010: effect of major pandemic threats,http://dx.doi.org/10.1186/1471-2458-13-1130,PMC4028814,24314008,CC BY,"BACKGROUND: Vaccination is the key measure available for prevention of the public health burden of annual influenza epidemics. This article describes national trends in seasonal influenza vaccine (IV) coverage in Portugal from 1998/99 to 2010/11, analyzes progress towards meeting WHO 2010 coverage goals, and addresses the effect of major public health threats of the last 12 years (SARS in 2003/04, influenza A (H5N1) in 2005/06, and the influenza A (H1N1)2009 pandemic) on vaccination trends. METHODS: The National Institute of Health surveyed (12 times) a random sample of Portuguese families. IV coverage was estimated and was adjusted for age distribution and country region. Independence of age and sex coverage distribution was tested using a modified F-statistic with a 5% significance level. The effect of SARS, A (H5N1), and the A (H1N1)2009 pandemic was tested using a meta-regression model. The model was adjusted for IV coverage in the general population and in the age groups. RESULTS: Between 1998/99 and 2010/11 IV, coverage in the general population varied between 14.2% (CI (95%): 11.6%–16.8%) and 17.5% (CI (95%): 17.6%–21.6%). There was no trend in coverage (p = 0.097). In the younger age group (<15 years) a declining trend was identified until 2008/09 (p = 0.005). This trend reversed in 2009/10. There was also a gradual and significant increase in seasonal IV coverage in the elderly (p for trend < 0.001). After 2006/07, IV coverage remained near 50%. Adjusting for baseline trends, there was significantly higher coverage in the general population in 2003/04 (p = 0.032) and 2005/06 (p = 0.018). The high coverage observed in the <15-year age group in season 2009/10 was also significant (p = 0.015). CONCLUSIONS: IV coverage in the elderly population displayed an increasing trend, but the 75% WHO 2010 target was not met. This result indicates that influenza vaccination strategy should be improved to meet the ambitious WHO coverage goals. The major pandemic threats of the past decade had a modest but significant effect on seasonal influenza vaccination. There was an increase in vaccine uptake proportion in the general population in 2003/04 and in 2005/06, and in individuals <15 years old in 2009/10.",2013 Dec 5,"['Pinto, Cátia Sousa', 'Nunes, Baltazar', 'Branco, Maria João', 'Falcão, José Marinho']",BMC Public Health,,,True
ab8da309a4060c4f4a3774c3ec9e7ebdc5a3a74e,PMC,α4-integrins control viral meningoencephalitis through differential recruitment of T helper cell subsets,http://dx.doi.org/10.1186/2051-5960-2-27,PMC4029267,24606807,CC BY,"INTRODUCTION: Natalizumab blocks α4-integrins and is a prototypic agent for a series of anti-inflammatory drugs that impair trafficking of immune cells into the CNS. However, modulation of the access of immune cells to the CNS is associated with impaired immune surveillance and detrimental viral infections of the CNS. Here, we explored the potency of cellular immune responses within the CNS to protect against viral encephalitis in mice with T cell conditional disruption of VLA-4 integrin (α4β1) expression. RESULTS: While VLA-4 expression in virus specific Th1 cells is non-redundant for their ability to access the CNS, α4-integrin deficient Th17 cells enter the CNS compartment and generate an inflammatory milieu upon intrathecal vaccinia virus (VV) infection. However, in contrast to Th1 cells that can adopt direct cytotoxic properties, Th17 cells fail to clear the virus due to insufficient Eomes induced perforin-1 expression. CONCLUSION: The quality of the intrathecal cellular antiviral response under conditions of impaired VLA-4 function jeopardizes host protection. Our functional in vivo data extend our mechanistic understanding of anti-viral immunity in the CNS and help to estimate the risk potential of upcoming therapeutic agents that target the trafficking of immune cells into distinct anatomical compartments.",2014 Mar 7,"['Rothhammer, Veit', 'Muschaweckh, Andreas', 'Gasteiger, Georg', 'Petermann, Franziska', 'Heink, Sylvia', 'Busch, Dirk H', 'Heikenwälder, Mathias', 'Hemmer, Bernhard', 'Drexler, Ingo', 'Korn, Thomas']",Acta Neuropathol Commun,,,True
36def2d37441d9ab0833ba1a1a48c68184bae246,PMC,Viral metagenomic analysis of feces of wild small carnivores,http://dx.doi.org/10.1186/1743-422X-11-89,PMC4030737,24886057,CC BY,"BACKGROUND: Recent studies have clearly demonstrated the enormous virus diversity that exists among wild animals. This exemplifies the required expansion of our knowledge of the virus diversity present in wildlife, as well as the potential transmission of these viruses to domestic animals or humans. METHODS: In the present study we evaluated the viral diversity of fecal samples (n = 42) collected from 10 different species of wild small carnivores inhabiting the northern part of Spain using random PCR in combination with next-generation sequencing. Samples were collected from American mink (Neovison vison), European mink (Mustela lutreola), European polecat (Mustela putorius), European pine marten (Martes martes), stone marten (Martes foina), Eurasian otter (Lutra lutra) and Eurasian badger (Meles meles) of the family of Mustelidae; common genet (Genetta genetta) of the family of Viverridae; red fox (Vulpes vulpes) of the family of Canidae and European wild cat (Felis silvestris) of the family of Felidae. RESULTS: A number of sequences of possible novel viruses or virus variants were detected, including a theilovirus, phleboviruses, an amdovirus, a kobuvirus and picobirnaviruses. CONCLUSIONS: Using random PCR in combination with next generation sequencing, sequences of various novel viruses or virus variants were detected in fecal samples collected from Spanish carnivores. Detected novel viruses highlight the viral diversity that is present in fecal material of wild carnivores.",2014 May 15,"['Bodewes, Rogier', 'Ruiz-Gonzalez, Aritz', 'Schapendonk, Claudia ME', 'van den Brand, Judith MA', 'Osterhaus, Albert DME', 'Smits, Saskia L']",Virol J,,,True
2bf9a03995b1056dc5d3e353461d3a31a9348885,PMC,Molecular Insights into Poly(ADP-ribose) Recognition and Processing,http://dx.doi.org/10.3390/biom3010001,PMC4030884,24970154,CC BY,"Poly(ADP-ribosyl)ation is a post-translational protein modification involved in the regulation of important cellular functions including DNA repair, transcription, mitosis and apoptosis. The amount of poly(ADP-ribosyl)ation (PAR) in cells reflects the balance of synthesis, mediated by the PARP protein family, and degradation, which is catalyzed by a glycohydrolase, PARG. Many of the proteins mediating PAR metabolism possess specialised high affinity PAR-binding modules that allow the efficient sensing or processing of the PAR signal. The identification of four such PAR-binding modules and the characterization of a number of proteins utilising these elements during the last decade has provided important insights into how PAR regulates different cellular activities. The macrodomain represents a unique PAR-binding module which is, in some instances, known to possess enzymatic activity on ADP-ribose derivatives (in addition to PAR-binding). The most recently discovered example for this is the PARG protein, and several available PARG structures have provided an understanding into how the PARG macrodomain evolved into a major enzyme that maintains PAR homeostasis in living cells.",2012 Dec 21,"['Žaja, Roko', 'Mikoč, Andreja', 'Barkauskaite, Eva', 'Ahel, Ivan']",Biomolecules,,,True
cfdfb727440e1010a4189d0c9bee58330c0383dc,PMC,The 3′-Terminal 55 Nucleotides of Bovine Coronavirus Defective Interfering RNA Harbor Cis-Acting Elements Required for Both Negative- and Positive-Strand RNA Synthesis,http://dx.doi.org/10.1371/journal.pone.0098422,PMC4031142,24852421,CC BY,"The synthesis of the negative-strand [(−)-strand] complement of the ∼30 kilobase, positive-strand [(+)-strand] coronaviral genome is a necessary early step for genome replication. The identification of cis-acting elements required for (−)-strand RNA synthesis in coronaviruses, however, has been hampered due to insufficiencies in the techniques used to detect the (−)-strand RNA species. Here, we employed a method of head-to-tail ligation and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) to detect and quantitate the synthesis of bovine coronavirus (BCoV) defective interfering (DI) RNA (−) strands. Furthermore, using the aforementioned techniques along with Northern blot assay, we specifically defined the cis-acting RNA elements within the 3′-terminal 55 nucleotides (nts) which function in the synthesis of (−)- or (+)-strand BCoV DI RNA. The major findings are as follows: (i) nts from -5 to -39 within the 3′-terminal 55 nts are the cis-acting elements responsible for (−)-strand BCoV DI RNA synthesis, (ii) nts from −3 to −34 within the 3′-terminal 55 nts are cis-acting elements required for (+)-strand BCoV DI RNA synthesis, and (iii) the nucleotide species at the 3′-most position (−1) is important, but not critical, for both (−)- and (+)-strand BCoV DI RNA synthesis. These results demonstrate that the 3′-terminal 55 nts in BCoV DI RNA harbor cis-acting RNA elements required for both (−)- and (+)-strand DI RNA synthesis and extend our knowledge on the mechanisms of coronavirus replication. The method of head-to-tail ligation and qRT-PCR employed in the study may also be applied to identify other cis-acting elements required for (−)-strand RNA synthesis in coronaviruses.",2014 May 22,"['Liao, Wei-Yu', 'Ke, Ting-Yung', 'Wu, Hung-Yi']",PLoS One,,,True
bc1beba35495c40001df667b4612b7cb9bb67185,PMC,One Health: Past Successes and Future Challenges in Three African Contexts,http://dx.doi.org/10.1371/journal.pntd.0002884,PMC4031173,24851901,CC BY,"BACKGROUND: The recent emergence of zoonotic diseases such as Highly Pathogenic Avian Influenza (HPAI) and Severe Acute Respiratory Syndrome (SARS) have contributed to dominant Global Health narratives around health securitisation and pandemic preparedness, calling for greater co-operation between the health, veterinary and environmental sectors in the ever-evolving One Health movement. A decade later, One Health advocates face increasing pressure to translate the approach from theory into action. METHODOLOGY/PRINCIPAL FINDINGS: A qualitative case study methodology was used to examine the emerging relationships between international One Health dialogue and its practical implementation in the African health policy context. A series of Key Informant Interviews (n = 32) with policy makers, government officials and academics in Nigeria, Tanzania and Uganda are presented as three separate case studies. Each case examines a significant aspect of One Health operationalisation, framed around the control of both emerging and Neglected Zoonotic Diseases including HPAI, Human African Trypanosomiasis and rabies. The research found that while there is general enthusiasm and a strong affirmative argument for adoption of One Health approaches in Africa, identifying alternative contexts away from a narrow focus on pandemics will help broaden its appeal, particularly for national or regionally significant endemic and neglected diseases not usually addressed under a “global” remit. CONCLUSIONS/SIGNIFICANCE: There is no ‘one size fits all’ approach to achieving the intersectoral collaboration, significant resource mobilisation and political co-operation required to realise a One Health approach. Individual country requirements cannot be underestimated, dismissed or prescribed in a top down manner. This article contributes to the growing discussion regarding not whether One Health should be operationalised, but how this may be achieved.",2014 May 22,"['Okello, Anna L.', 'Bardosh, Kevin', 'Smith, James', 'Welburn, Susan C.']",PLoS Negl Trop Dis,,,True
b7b6bf20c919a0b200c528e76f76f508d5554700,PMC,Structural Basis for the Ubiquitin-Linkage Specificity and deISGylating Activity of SARS-CoV Papain-Like Protease,http://dx.doi.org/10.1371/journal.ppat.1004113,PMC4031219,24854014,CC BY,"Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes a papain-like protease (PLpro) with both deubiquitinating (DUB) and deISGylating activities that are proposed to counteract the post-translational modification of signaling molecules that activate the innate immune response. Here we examine the structural basis for PLpro's ubiquitin chain and interferon stimulated gene 15 (ISG15) specificity. We present the X-ray crystal structure of PLpro in complex with ubiquitin-aldehyde and model the interaction of PLpro with other ubiquitin-chain and ISG15 substrates. We show that PLpro greatly prefers K48- to K63-linked ubiquitin chains, and ISG15-based substrates to those that are mono-ubiquitinated. We propose that PLpro's higher affinity for K48-linked ubiquitin chains and ISG15 stems from a bivalent mechanism of binding, where two ubiquitin-like domains prefer to bind in the palm domain of PLpro with the most distal ubiquitin domain interacting with a “ridge” region of the thumb domain. Mutagenesis of residues within this ridge region revealed that these mutants retain viral protease activity and the ability to catalyze hydrolysis of mono-ubiquitin. However, a select number of these mutants have a significantly reduced ability to hydrolyze the substrate ISG15-AMC, or be inhibited by K48-linked diubuiquitin. For these latter residues, we found that PLpro antagonism of the nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) signaling pathway is abrogated. This identification of key and unique sites in PLpro required for recognition and processing of diubiquitin and ISG15 versus mono-ubiquitin and protease activity provides new insight into ubiquitin-chain and ISG15 recognition and highlights a role for PLpro DUB and deISGylase activity in antagonism of the innate immune response.",2014 May 22,"['Ratia, Kiira', 'Kilianski, Andrew', 'Baez-Santos, Yahira M.', 'Baker, Susan C.', 'Mesecar, Andrew']",PLoS Pathog,,,True
2074bedae293a25ea9023dc8802bd67b3a626b83,PMC,Structural Basis for the Ubiquitin-Linkage Specificity and deISGylating Activity of SARS-CoV Papain-Like Protease,http://dx.doi.org/10.1371/journal.ppat.1004113,PMC4031219,24854014,CC BY,"Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes a papain-like protease (PLpro) with both deubiquitinating (DUB) and deISGylating activities that are proposed to counteract the post-translational modification of signaling molecules that activate the innate immune response. Here we examine the structural basis for PLpro's ubiquitin chain and interferon stimulated gene 15 (ISG15) specificity. We present the X-ray crystal structure of PLpro in complex with ubiquitin-aldehyde and model the interaction of PLpro with other ubiquitin-chain and ISG15 substrates. We show that PLpro greatly prefers K48- to K63-linked ubiquitin chains, and ISG15-based substrates to those that are mono-ubiquitinated. We propose that PLpro's higher affinity for K48-linked ubiquitin chains and ISG15 stems from a bivalent mechanism of binding, where two ubiquitin-like domains prefer to bind in the palm domain of PLpro with the most distal ubiquitin domain interacting with a “ridge” region of the thumb domain. Mutagenesis of residues within this ridge region revealed that these mutants retain viral protease activity and the ability to catalyze hydrolysis of mono-ubiquitin. However, a select number of these mutants have a significantly reduced ability to hydrolyze the substrate ISG15-AMC, or be inhibited by K48-linked diubuiquitin. For these latter residues, we found that PLpro antagonism of the nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) signaling pathway is abrogated. This identification of key and unique sites in PLpro required for recognition and processing of diubiquitin and ISG15 versus mono-ubiquitin and protease activity provides new insight into ubiquitin-chain and ISG15 recognition and highlights a role for PLpro DUB and deISGylase activity in antagonism of the innate immune response.",2014 May 22,"['Ratia, Kiira', 'Kilianski, Andrew', 'Baez-Santos, Yahira M.', 'Baker, Susan C.', 'Mesecar, Andrew']",PLoS Pathog,,,False
18adcbf84b2bc81951a30bad117fc8d0a3cc623e,PMC,Structural Basis for the Ubiquitin-Linkage Specificity and deISGylating Activity of SARS-CoV Papain-Like Protease,http://dx.doi.org/10.1371/journal.ppat.1004113,PMC4031219,24854014,CC BY,"Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes a papain-like protease (PLpro) with both deubiquitinating (DUB) and deISGylating activities that are proposed to counteract the post-translational modification of signaling molecules that activate the innate immune response. Here we examine the structural basis for PLpro's ubiquitin chain and interferon stimulated gene 15 (ISG15) specificity. We present the X-ray crystal structure of PLpro in complex with ubiquitin-aldehyde and model the interaction of PLpro with other ubiquitin-chain and ISG15 substrates. We show that PLpro greatly prefers K48- to K63-linked ubiquitin chains, and ISG15-based substrates to those that are mono-ubiquitinated. We propose that PLpro's higher affinity for K48-linked ubiquitin chains and ISG15 stems from a bivalent mechanism of binding, where two ubiquitin-like domains prefer to bind in the palm domain of PLpro with the most distal ubiquitin domain interacting with a “ridge” region of the thumb domain. Mutagenesis of residues within this ridge region revealed that these mutants retain viral protease activity and the ability to catalyze hydrolysis of mono-ubiquitin. However, a select number of these mutants have a significantly reduced ability to hydrolyze the substrate ISG15-AMC, or be inhibited by K48-linked diubuiquitin. For these latter residues, we found that PLpro antagonism of the nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) signaling pathway is abrogated. This identification of key and unique sites in PLpro required for recognition and processing of diubiquitin and ISG15 versus mono-ubiquitin and protease activity provides new insight into ubiquitin-chain and ISG15 recognition and highlights a role for PLpro DUB and deISGylase activity in antagonism of the innate immune response.",2014 May 22,"['Ratia, Kiira', 'Kilianski, Andrew', 'Baez-Santos, Yahira M.', 'Baker, Susan C.', 'Mesecar, Andrew']",PLoS Pathog,,,False
4d968bbfddfa8eb4f1cad1f00ed121ec2c4a4df6,PMC,A new paradigm: innate immune sensing of viruses via the unfolded protein response,http://dx.doi.org/10.3389/fmicb.2014.00222,PMC4032990,24904537,CC BY,"The immune system depends upon combinations of signals to mount appropriate responses: pathogen specific signals in the context of co-stimulatory “danger” signals drive immune strength and accuracy. Viral infections trigger anti-viral type I interferon (IFN) responses by stimulating endosomal and cytosolic pattern recognition receptors (PRRs). However, viruses have also evolved many strategies to counteract IFN responses. Are there intracellular danger signals that enhance immune responses to viruses? During infection, viruses place a heavy demand on the protein folding machinery of the host endoplasmic reticulum (ER). To survive ER stress, host cells mount an unfolded protein response (UPR) to decrease ER protein load and enhance protein-folding capacity. Viruses also directly elicit the UPR to enhance their replication. Increasing evidence supports an intersection between the host UPR and inflammation, in particular the production of pro-inflammatory cytokines and type I IFN. The UPR directly activates pro-inflammatory cytokine transcription factors and dramatically enhances cytokine production in response to viral PRR engagement. Additionally, viral PRR engagement may stimulate specific pathways within the UPR to enhance cytokine production. Through these mechanisms, viral detection via the UPR and inflammatory cytokine production are intertwined. Consequently, the UPR response is perfectly poised to act as an infection-triggered “danger” signal. The UPR may serve as an internal “co-stimulatory” signal that (1) provides specificity and (2) critically augments responses to overcome viral subterfuge. Further work is needed to test this hypothesis during viral infections.",2014 May 16,"Smith, Judith A.",Front Microbiol,,,True
78b3f2e613d0e2be8608c68c73b20c25d440a0b8,PMC,Unfolded protein response in hepatitis C virus infection,http://dx.doi.org/10.3389/fmicb.2014.00233,PMC4033015,24904547,CC BY,"Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus of clinical importance. The virus establishes a chronic infection and can progress from chronic hepatitis, steatosis to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The mechanisms of viral persistence and pathogenesis are poorly understood. Recently the unfolded protein response (UPR), a cellular homeostatic response to endoplasmic reticulum (ER) stress, has emerged to be a major contributing factor in many human diseases. It is also evident that viruses interact with the host UPR in many different ways and the outcome could be pro-viral, anti-viral or pathogenic, depending on the particular type of infection. Here we present evidence for the elicitation of chronic ER stress in HCV infection. We analyze the UPR signaling pathways involved in HCV infection, the various levels of UPR regulation by different viral proteins and finally, we propose several mechanisms by which the virus provokes the UPR.",2014 May 20,"Chan, Shiu-Wan",Front Microbiol,,,True
488e1294b604a8ea66aa4f21f431b52723dfc8de,PMC,"Enterovirus 71 related severe hand, foot and mouth disease outbreaks in South-East Asia: current situation and ongoing challenges",http://dx.doi.org/10.1136/jech-2014-203836,PMC4033151,24652348,CC BY,,2014 Jun 20,"['Sabanathan, Saraswathy', 'Tan, Le Van', 'Thwaites, Louise', 'Wills, Bridget', 'Qui, Phan Tu', 'Rogier van Doorn, H']",J Epidemiol Community Health,,,True
6b3f7521b0b4ed6a0230e0ce6ab2f4c02892a287,PMC,Epidemiology of virus-induced asthma exacerbations: with special reference to the role of human rhinovirus,http://dx.doi.org/10.3389/fmicb.2014.00226,PMC4033317,24904541,CC BY,"Viral respiratory infections may be associated with the virus-induced asthma in adults as well as children. Particularly, human rhinovirus is strongly suggested a major candidate for the associations of the virus-induced asthma. Thus, in this review, we reviewed and focused on the epidemiology, pathophysiology, and treatment of virus-induced asthma with special reference on human rhinovirus. Furthermore, we added our preliminary data regarding the clinical and virological findings in the present review.",2014 May 26,"['Saraya, Takeshi', 'Kurai, Daisuke', 'Ishii, Haruyuki', 'Ito, Anri', 'Sasaki, Yoshiko', 'Niwa, Shoichi', 'Kiyota, Naoko', 'Tsukagoshi, Hiroyuki', 'Kozawa, Kunihisa', 'Goto, Hajime', 'Takizawa, Hajime']",Front Microbiol,,,True
cbc8e184157e7543e44f09f2be3999131db359e2,PMC,Comparative Analysis of Lycorine in Wild Plant and Callus Culture Samples of Hymenocallis littoralis by HPLC-UV Method,http://dx.doi.org/10.1155/2014/408306,PMC4033353,24895650,CC BY,"The Hymenocallis littoralis, an ornamental and medicinal plant, had been traditionally used for wound healing. In the present study, an analytical method using HPLC with ultraviolet detection was developed for the quantification of lycorine in the extracts of different parts of wild plant and tissue culture samples of H. littoralis. The separation was achieved using a reversed-phase column. The method was found to be accurate, repeatable, and sensitive for the quantification of minute amount of lycorine present in the samples. The highest lycorine content was found in the bulb extract (2.54 ± 0.02 μg/mg) whereas the least was in the root extract (0.71 ± 0.02 μg/mg) of the wild plants. Few callus culture samples had high content of lycorine, comparable to that of wild plants. The results showed that plant growth regulators, 2,4-dichlorophenoxyacetic acid (2,4-D) alone at 4.5 μM (2.58 ± 0.38 μg/mg) or a combination of 2,4-D at 9.00 μM with 4.5 μM of 6-benzylaminopurine (BAP), were the optimum concentrations for the production of high lycorine (2.45 ± 0.15 μg/mg) content in callus culture. The present analytical method could be of value for routine quantification of lycorine in the tissue culture production and standardization of the raw material or extracts of H. littoralis.",2014 May 6,"['Subramaniam, Sreeramanan', 'Sundarasekar, Jeevandran', 'Sahgal, Geethaa', 'Murugaiyah, Vikneswaran']",ScientificWorldJournal,,,True
d0a6596fcbf8b76491fd4f2c4da8d9037170caf8,PMC,Cellular unfolded protein response against viruses used in gene therapy,http://dx.doi.org/10.3389/fmicb.2014.00250,PMC4033601,24904562,CC BY,"Viruses are excellent vehicles for gene therapy due to their natural ability to infect and deliver the cargo to specific tissues with high efficiency. Although such vectors are usually “gutted” and are replication defective, they are subjected to clearance by the host cells by immune recognition and destruction. Unfolded protein response (UPR) is a naturally evolved cyto-protective signaling pathway which is triggered due to endoplasmic reticulum (ER) stress caused by accumulation of unfolded/misfolded proteins in its lumen. The UPR signaling consists of three signaling pathways, namely PKR-like ER kinase, activating transcription factor 6, and inositol-requiring protein-1. Once activated, UPR triggers the production of ER molecular chaperones and stress response proteins to help reduce the protein load within the ER. This occurs by degradation of the misfolded proteins and ensues in the arrest of protein translation machinery. If the burden of protein load in ER is beyond its processing capacity, UPR can activate pro-apoptotic pathways or autophagy leading to cell death. Viruses are naturally evolved in hijacking the host cellular translation machinery to generate a large amount of proteins. This phenomenon disrupts ER homeostasis and leads to ER stress. Alternatively, in the case of gutted vectors used in gene therapy, the excess load of recombinant vectors administered and encountered by the cell can trigger UPR. Thus, in the context of gene therapy, UPR becomes a major roadblock that can potentially trigger inflammatory responses against the vectors and reduce the efficiency of gene transfer.",2014 May 26,"['Sen, Dwaipayan', 'Balakrishnan, Balaji', 'Jayandharan, Giridhara R.']",Front Microbiol,,,True
46c2eb2186aa09c3963227ce0195a881ac26de7d,PMC,Cell-Penetrating Peptides for Antiviral Drug Development,http://dx.doi.org/10.3390/ph3030448,PMC4033964,27713263,CC BY,"Viral diseases affect hundreds of millions of people worldwide, and the few available drugs to treat these diseases often come with limitations. The key obstacle to the development of new antiviral agents is their delivery into infected cells in vivo. Cell-penetrating peptides (CPPs) are short peptides that can cross the cellular lipid bilayer with the remarkable capability to shuttle conjugated cargoes into cells. CPPs have been successfully utilized to enhance the cellular uptake and intracellular trafficking of antiviral molecules, and thereby increase the inhibitory activity of potential antiviral proteins and oligonucleotide analogues, both in cultured cells and in animal models. This review will address the notable findings of these studies, highlighting some promising results and discussing the challenges CPP technology has to overcome for further clinical applications.",2010 Mar 2,"['Delcroix, Melaine', 'Riley, Lee W.']",Pharmaceuticals (Basel),,,True
b94bee4f159369de60f7d9e7cc5733676dfa15b8,PMC,Building Cell Selectivity into CPP-Mediated Strategies,http://dx.doi.org/10.3390/ph3051456,PMC4033992,27713313,CC BY,"There is a pressing need for more effective and selective therapies for cancer and other diseases. Consequently, much effort is being devoted to the development of alternative experimental approaches based on selective systems, which are designed to be specifically directed against target cells. In addition, a large number of highly potent therapeutic molecules are being discovered. However, they do not reach clinical trials because of their low delivery, poor specificity or their incapacity to bypass the plasma membrane. Cell-penetrating peptides (CPPs) are an open door for cell-impermeable compounds to reach intracellular targets. Putting all these together, research is sailing in the direction of the design of systems with the capacity to transport new drugs into a target cell. Some CPPs show cell type specificity while others require modifications or form part of more sophisticated drug delivery systems. In this review article we summarize several strategies for directed drug delivery involving CPPs that have been reported in the literature.",2010 May 14,"['Martín, Irene', 'Teixidó, Meritxell', 'Giralt, Ernest']",Pharmaceuticals (Basel),,,True
8446bfae882d6ec192e572e9bbcb858eeae83cc8,PMC,DV-Curve Representation of Protein Sequences and Its Application,http://dx.doi.org/10.1155/2014/203871,PMC4034481,24899916,CC BY,"Based on the detailed hydrophobic-hydrophilic(HP) model of amino acids, we propose dual-vector curve (DV-curve) representation of protein sequences, which uses two vectors to represent one alphabet of protein sequences. This graphical representation not only avoids degeneracy, but also has good visualization no matter how long these sequences are, and can reflect the length of protein sequence. Then we transform the 2D-graphical representation into a numerical characterization that can facilitate quantitative comparison of protein sequences. The utility of this approach is illustrated by two examples: one is similarity/dissimilarity comparison among different ND6 protein sequences based on their DV-curve figures the other is the phylogenetic analysis among coronaviruses based on their spike proteins.",2014 May 8,"['Deng, Wei', 'Luan, Yihui']",Comput Math Methods Med,,,True
33222702ba2e2e7e5f526c667d64beb5bd2cda96,PMC,Improving the estimation of the death rate of infected cells from time course data during the acute phase of virus infections: application to acute HIV-1 infection in a humanized mouse model,http://dx.doi.org/10.1186/1742-4682-11-22,PMC4035760,24885827,CC BY,"BACKGROUND: Mathematical modeling of virus dynamics has provided quantitative insights into viral infections such as influenza, the simian immunodeficiency virus/human immunodeficiency virus, hepatitis B, and hepatitis C. Through modeling, we can estimate the half-life of infected cells, the exponential growth rate, and the basic reproduction number (R(0)). To calculate R(0) from virus load data, the death rate of productively infected cells is required. This can be readily estimated from treatment data collected during the chronic phase, but is difficult to determine from acute infection data. Here, we propose two new models that can reliably estimate the average life span of infected cells from acute-phase data, and apply both methods to experimental data from humanized mice infected with HIV-1. METHODS: Both new models, called as the reduced quasi-steady state (RQS) model and the piece-wise regression (PWR) model, are derived by simplification of a standard model for the acute-phase dynamics of target cells, viruses and infected cells. By having only a limited number of parameters, both models allow us to reliably estimate the death rate of productively infected cells. Simulated datasets with plausible parameter values are generated with the standard model to compare the performance of the new models with that of the major previous model (i.e., the simple exponential model). Finally, we fit models to time course data from HIV-1 infected humanized mice to estimate the several important parameters characterizing their acute infection. RESULTS AND CONCLUSIONS: The new models provided much better estimates than the previous model because they more precisely capture the de novo infection process. Both models describe the acute phase of HIV-1 infected humanized mice reasonably well, and we estimated an average death rate of infected cells of 0.61 and 0.61, an average exponential growth rate of 0.69 and 0.76, and an average basic reproduction number of 2.30 and 2.38 in the RQS model and the PWR model, respectively. These estimates are fairly close to those obtained in humans.",2014 May 21,"['Ikeda, Hiroki', 'de Boer, Rob J', 'Sato, Kei', 'Morita, Satoru', 'Misawa, Naoko', 'Koyanagi, Yoshio', 'Aihara, Kazuyuki', 'Iwami, Shingo']",Theor Biol Med Model,,,True
d33a044bbb52673f1eeeb792b0376b0987fe02f6,PMC,Evaluation of the Broad-Range PCR-Electrospray Ionization Mass Spectrometry (PCR/ESI-MS) System and Virus Microarrays for Virus Detection,http://dx.doi.org/10.3390/v6051876,PMC4036539,24777034,CC BY,"Advanced nucleic acid-based technologies are powerful research tools for novel virus discovery but need to be standardized for broader applications such as virus detection in biological products and clinical samples. We have used well-characterized retrovirus stocks to evaluate the limit of detection (LOD) for broad-range PCR with electrospray ionization mass spectrometry (PCR/ESI-MS or PLEX-ID), RT-PCR assays, and virus microarrays. The results indicated that in the absence of background cellular nucleic acids, PLEX-ID and RT-PCR had a similar LOD for xenotropic murine retrovirus-related virus (XMRV; 3.12 particles per µL) whereas sensitivity of virus detection was 10-fold greater using virus microarrays. When virus was spiked into a background of cellular nucleic acids, the LOD using PLEX-ID remained the same, whereas virus detection by RT-PCR was 10-fold less sensitive, and no virus could be detected by microarrays. Expected endogenous retrovirus (ERV) sequences were detected in cell lines tested and known species-specific viral sequences were detected in bovine serum and porcine trypsin. A follow-up strategy was developed using PCR amplification, nucleotide sequencing, and bioinformatics to demonstrate that an RD114-like retrovirus sequence that was detected by PLEX-ID in canine cell lines (Madin-Darby canine kidney (MDCK) and Cf2Th canine thymus) was due to defective, endogenous gammaretrovirus-related sequences.",2014 Apr 25,"['Taliaferro, Lanyn P.', 'Galvin, Teresa A.', 'Ma, Hailun', 'Shaheduzzaman, Syed', 'Williams, Dhanya K.', 'Glasner, Dustin R.', 'Khan, Arifa S.']",Viruses,,,True
baf2944b65112b4b45b0c0f6aeb16e3e90a4f61e,PMC,Hantavirus Reservoirs: Current Status with an Emphasis on Data from Brazil,http://dx.doi.org/10.3390/v6051929,PMC4036540,24784571,CC BY,"Since the recognition of hantavirus as the agent responsible for haemorrhagic fever in Eurasia in the 1970s and, 20 years later, the descovery of hantavirus pulmonary syndrome in the Americas, the genus Hantavirus has been continually described throughout the World in a variety of wild animals. The diversity of wild animals infected with hantaviruses has only recently come into focus as a result of expanded wildlife studies. The known reservoirs are more than 80, belonging to 51 species of rodents, 7 bats (order Chiroptera) and 20 shrews and moles (order Soricomorpha). More than 80genetically related viruses have been classified within Hantavirus genus; 25 recognized as human pathogens responsible for a large spectrum of diseases in the Old and New World. In Brazil, where the diversity of mammals and especially rodents is considered one of the largest in the world, 9 hantavirus genotypes have been identified in 12 rodent species belonging to the genus Akodon, Calomys, Holochilus, Oligoryzomys, Oxymycterus, Necromys and Rattus. Considering the increasing number of animals that have been implicated as reservoirs of different hantaviruses, the understanding of this diversity is important for evaluating the risk of distinct hantavirus species as human pathogens.",2014 Apr 29,"['Carvalho de Oliveira, Renata', 'Guterres, Alexandro', 'Fernandes, Jorlan', 'D’Andrea, Paulo Sérgio', 'Bonvicino, Cibele Rodrigues', 'de Lemos, Elba Regina Sampaio']",Viruses,,,True
50e19c5dc4c5f5934e19be3082fb5aca082870fb,PMC,Hantavirus Reservoirs: Current Status with an Emphasis on Data from Brazil,http://dx.doi.org/10.3390/v6051929,PMC4036540,24784571,CC BY,"Since the recognition of hantavirus as the agent responsible for haemorrhagic fever in Eurasia in the 1970s and, 20 years later, the descovery of hantavirus pulmonary syndrome in the Americas, the genus Hantavirus has been continually described throughout the World in a variety of wild animals. The diversity of wild animals infected with hantaviruses has only recently come into focus as a result of expanded wildlife studies. The known reservoirs are more than 80, belonging to 51 species of rodents, 7 bats (order Chiroptera) and 20 shrews and moles (order Soricomorpha). More than 80genetically related viruses have been classified within Hantavirus genus; 25 recognized as human pathogens responsible for a large spectrum of diseases in the Old and New World. In Brazil, where the diversity of mammals and especially rodents is considered one of the largest in the world, 9 hantavirus genotypes have been identified in 12 rodent species belonging to the genus Akodon, Calomys, Holochilus, Oligoryzomys, Oxymycterus, Necromys and Rattus. Considering the increasing number of animals that have been implicated as reservoirs of different hantaviruses, the understanding of this diversity is important for evaluating the risk of distinct hantavirus species as human pathogens.",2014 Apr 29,"['Carvalho de Oliveira, Renata', 'Guterres, Alexandro', 'Fernandes, Jorlan', 'D’Andrea, Paulo Sérgio', 'Bonvicino, Cibele Rodrigues', 'de Lemos, Elba Regina Sampaio']",Viruses,,,False
03148d1ba3c986ec7306ab2a90bcd6082c512f49,PMC,Evidence for Retrovirus and Paramyxovirus Infection of Multiple Bat Species in China,http://dx.doi.org/10.3390/v6052138,PMC4036550,24841387,CC BY,"Bats are recognized reservoirs for many emerging zoonotic viruses of public health importance. Identifying and cataloguing the viruses of bats is a logical approach to evaluate the range of potential zoonoses of bat origin. We characterized the fecal pathogen microbiome of both insectivorous and frugivorous bats, incorporating 281 individual bats comprising 20 common species, which were sampled in three locations of Yunnan province, by combining reverse transcription polymerase chain reaction (RT-PCR) assays and next-generation sequencing. Seven individual bats were paramyxovirus-positive by RT-PCR using degenerate primers, and these paramyxoviruses were mainly classified into three genera (Rubulavirus, Henipavirus and Jeilongvirus). Various additional novel pathogens were detected in the paramyxovirus-positive bats using Illumina sequencing. A total of 7066 assembled contigs (≥200 bp) were constructed, and 105 contigs matched eukaryotic viruses (of them 103 belong to 2 vertebrate virus families, 1 insect virus, and 1 mycovirus), 17 were parasites, and 4913 were homologous to prokaryotic microorganisms. Among the 103 vertebrate viral contigs, 79 displayed low identity (<70%) to known viruses including human viruses at the amino acid level, suggesting that these belong to novel and genetically divergent viruses. Overall, the most frequently identified viruses, particularly in bats from the family Hipposideridae, were retroviruses. The present study expands our understanding of the bat virome in species commonly found in Yunnan, China, and provides insight into the overall diversity of viruses that may be capable of directly or indirectly crossing over into humans.",2014 May 16,"['Yuan, Lihong', 'Li, Min', 'Li, Linmiao', 'Monagin, Corina', 'Chmura, Aleksei A.', 'Schneider, Bradley S.', 'Epstein, Jonathan H.', 'Mei, Xiaolin', 'Shi, Zhengli', 'Daszak, Peter', 'Chen, Jinping']",Viruses,,,True
247a9eae1e4452f7f969ab41a88f335fda54fbc9,PMC,Evidence for Retrovirus and Paramyxovirus Infection of Multiple Bat Species in China,http://dx.doi.org/10.3390/v6052138,PMC4036550,24841387,CC BY,"Bats are recognized reservoirs for many emerging zoonotic viruses of public health importance. Identifying and cataloguing the viruses of bats is a logical approach to evaluate the range of potential zoonoses of bat origin. We characterized the fecal pathogen microbiome of both insectivorous and frugivorous bats, incorporating 281 individual bats comprising 20 common species, which were sampled in three locations of Yunnan province, by combining reverse transcription polymerase chain reaction (RT-PCR) assays and next-generation sequencing. Seven individual bats were paramyxovirus-positive by RT-PCR using degenerate primers, and these paramyxoviruses were mainly classified into three genera (Rubulavirus, Henipavirus and Jeilongvirus). Various additional novel pathogens were detected in the paramyxovirus-positive bats using Illumina sequencing. A total of 7066 assembled contigs (≥200 bp) were constructed, and 105 contigs matched eukaryotic viruses (of them 103 belong to 2 vertebrate virus families, 1 insect virus, and 1 mycovirus), 17 were parasites, and 4913 were homologous to prokaryotic microorganisms. Among the 103 vertebrate viral contigs, 79 displayed low identity (<70%) to known viruses including human viruses at the amino acid level, suggesting that these belong to novel and genetically divergent viruses. Overall, the most frequently identified viruses, particularly in bats from the family Hipposideridae, were retroviruses. The present study expands our understanding of the bat virome in species commonly found in Yunnan, China, and provides insight into the overall diversity of viruses that may be capable of directly or indirectly crossing over into humans.",2014 May 16,"['Yuan, Lihong', 'Li, Min', 'Li, Linmiao', 'Monagin, Corina', 'Chmura, Aleksei A.', 'Schneider, Bradley S.', 'Epstein, Jonathan H.', 'Mei, Xiaolin', 'Shi, Zhengli', 'Daszak, Peter', 'Chen, Jinping']",Viruses,,,True
b53f3fa13a84fed43c6314ae35e98f59eb54c9e9,PMC,On-farm biosecurity as perceived by professionals visiting Swedish farms,http://dx.doi.org/10.1186/1751-0147-56-28,PMC4036743,24886408,CC BY,"BACKGROUND: On-farm biosecurity is an important part of disease prevention and control, this applies to live animal contacts as well as indirect contacts e.g. via professionals visiting farms in their work. The objectives of this study were to investigate how professionals visiting animal farms in Sweden in their daily work perceive the on-farm conditions for biosecurity, the factors that influence their own biosecurity routines and what they describe as obstacles for biosecurity. Suggestions for improvements were also asked for. Questionnaires were distributed to professionals visiting farms in their daily work; veterinarians, livestock hauliers, artificial insemination technicians, animal welfare inspectors and cattle hoof trimmers. The sample was a convenience sample, based on accessibility to registers or collaboration with organisations distributing the questionnaire. Respondents were asked about the availability of certain biosecurity conditions related to farm visits, e.g. if facilities for hand washing were available, how important different factors were for their own routines and, through open ended questions, to describe obstacles and suggestions for improvement. RESULTS: After data cleaning, there were responses from 368 persons. There was a difference in the proportion of visited farms reported to have certain biosecurity measures in place related to animal species present on the farm. In general, visited pig farms had a higher proportion of biosecurity measures in place, whereas the conditions were poorer on sheep and goat farms and horse farms. There were also differences between the visitor categories; the perceived conditions for biosecurity varied between the groups, e.g. livestock hauliers did not have access to hand washing facilities as often as veterinarians did. In all groups, a majority of the respondents perceived obstacles for on-farm biosecurity, among veterinarians 66% perceived that there were obstacles. Many of the reported obstacles related to the very basics of biosecurity, such as access to soap and water. Responsibility was identified to be a key issue; while some farmers expect visitors to take responsibility for keeping up biosecurity they do not provide the adequate on-farm conditions. CONCLUSIONS: Many of the respondents reported obstacles for keeping good biosecurity related to on-farm conditions. There was a gap when it came to responsibility which needs to be clarified. Visitors need to take responsibility for avoiding spread of disease, while farmers need to assume responsibility for providing adequate conditions for on-farm biosecurity.",2014 May 9,"['Nöremark, Maria', 'Sternberg-Lewerin, Susanna']",Acta Vet Scand,,,True
b1926f529e31d88fd6796fdae1916ced6d609c44,PMC,On-farm biosecurity as perceived by professionals visiting Swedish farms,http://dx.doi.org/10.1186/1751-0147-56-28,PMC4036743,24886408,CC BY,"BACKGROUND: On-farm biosecurity is an important part of disease prevention and control, this applies to live animal contacts as well as indirect contacts e.g. via professionals visiting farms in their work. The objectives of this study were to investigate how professionals visiting animal farms in Sweden in their daily work perceive the on-farm conditions for biosecurity, the factors that influence their own biosecurity routines and what they describe as obstacles for biosecurity. Suggestions for improvements were also asked for. Questionnaires were distributed to professionals visiting farms in their daily work; veterinarians, livestock hauliers, artificial insemination technicians, animal welfare inspectors and cattle hoof trimmers. The sample was a convenience sample, based on accessibility to registers or collaboration with organisations distributing the questionnaire. Respondents were asked about the availability of certain biosecurity conditions related to farm visits, e.g. if facilities for hand washing were available, how important different factors were for their own routines and, through open ended questions, to describe obstacles and suggestions for improvement. RESULTS: After data cleaning, there were responses from 368 persons. There was a difference in the proportion of visited farms reported to have certain biosecurity measures in place related to animal species present on the farm. In general, visited pig farms had a higher proportion of biosecurity measures in place, whereas the conditions were poorer on sheep and goat farms and horse farms. There were also differences between the visitor categories; the perceived conditions for biosecurity varied between the groups, e.g. livestock hauliers did not have access to hand washing facilities as often as veterinarians did. In all groups, a majority of the respondents perceived obstacles for on-farm biosecurity, among veterinarians 66% perceived that there were obstacles. Many of the reported obstacles related to the very basics of biosecurity, such as access to soap and water. Responsibility was identified to be a key issue; while some farmers expect visitors to take responsibility for keeping up biosecurity they do not provide the adequate on-farm conditions. CONCLUSIONS: Many of the respondents reported obstacles for keeping good biosecurity related to on-farm conditions. There was a gap when it came to responsibility which needs to be clarified. Visitors need to take responsibility for avoiding spread of disease, while farmers need to assume responsibility for providing adequate conditions for on-farm biosecurity.",2014 May 9,"['Nöremark, Maria', 'Sternberg-Lewerin, Susanna']",Acta Vet Scand,,,False
1cd5431db44d6562cfea3d77b51e079b13bc917f,PMC,On-farm biosecurity as perceived by professionals visiting Swedish farms,http://dx.doi.org/10.1186/1751-0147-56-28,PMC4036743,24886408,CC BY,"BACKGROUND: On-farm biosecurity is an important part of disease prevention and control, this applies to live animal contacts as well as indirect contacts e.g. via professionals visiting farms in their work. The objectives of this study were to investigate how professionals visiting animal farms in Sweden in their daily work perceive the on-farm conditions for biosecurity, the factors that influence their own biosecurity routines and what they describe as obstacles for biosecurity. Suggestions for improvements were also asked for. Questionnaires were distributed to professionals visiting farms in their daily work; veterinarians, livestock hauliers, artificial insemination technicians, animal welfare inspectors and cattle hoof trimmers. The sample was a convenience sample, based on accessibility to registers or collaboration with organisations distributing the questionnaire. Respondents were asked about the availability of certain biosecurity conditions related to farm visits, e.g. if facilities for hand washing were available, how important different factors were for their own routines and, through open ended questions, to describe obstacles and suggestions for improvement. RESULTS: After data cleaning, there were responses from 368 persons. There was a difference in the proportion of visited farms reported to have certain biosecurity measures in place related to animal species present on the farm. In general, visited pig farms had a higher proportion of biosecurity measures in place, whereas the conditions were poorer on sheep and goat farms and horse farms. There were also differences between the visitor categories; the perceived conditions for biosecurity varied between the groups, e.g. livestock hauliers did not have access to hand washing facilities as often as veterinarians did. In all groups, a majority of the respondents perceived obstacles for on-farm biosecurity, among veterinarians 66% perceived that there were obstacles. Many of the reported obstacles related to the very basics of biosecurity, such as access to soap and water. Responsibility was identified to be a key issue; while some farmers expect visitors to take responsibility for keeping up biosecurity they do not provide the adequate on-farm conditions. CONCLUSIONS: Many of the respondents reported obstacles for keeping good biosecurity related to on-farm conditions. There was a gap when it came to responsibility which needs to be clarified. Visitors need to take responsibility for avoiding spread of disease, while farmers need to assume responsibility for providing adequate conditions for on-farm biosecurity.",2014 May 9,"['Nöremark, Maria', 'Sternberg-Lewerin, Susanna']",Acta Vet Scand,,,False
dc1e16996462dd1445f21c419b6e40dd0dd84c02,PMC,Asymmetrically interacting spreading dynamics on complex layered networks,http://dx.doi.org/10.1038/srep05097,PMC4037715,24872257,CC BY,"The spread of disease through a physical-contact network and the spread of information about the disease on a communication network are two intimately related dynamical processes. We investigate the asymmetrical interplay between the two types of spreading dynamics, each occurring on its own layer, by focusing on the two fundamental quantities underlying any spreading process: epidemic threshold and the final infection ratio. We find that an epidemic outbreak on the contact layer can induce an outbreak on the communication layer, and information spreading can effectively raise the epidemic threshold. When structural correlation exists between the two layers, the information threshold remains unchanged but the epidemic threshold can be enhanced, making the contact layer more resilient to epidemic outbreak. We develop a physical theory to understand the intricate interplay between the two types of spreading dynamics.",2014 May 29,"['Wang, Wei', 'Tang, Ming', 'Yang, Hui', 'Younghae Do', 'Lai, Ying-Cheng', 'Lee, GyuWon']",Sci Rep,,,True
354a4b199eb297756554a8967154ea32f07e88d1,PMC,Asymmetrically interacting spreading dynamics on complex layered networks,http://dx.doi.org/10.1038/srep05097,PMC4037715,24872257,CC BY,"The spread of disease through a physical-contact network and the spread of information about the disease on a communication network are two intimately related dynamical processes. We investigate the asymmetrical interplay between the two types of spreading dynamics, each occurring on its own layer, by focusing on the two fundamental quantities underlying any spreading process: epidemic threshold and the final infection ratio. We find that an epidemic outbreak on the contact layer can induce an outbreak on the communication layer, and information spreading can effectively raise the epidemic threshold. When structural correlation exists between the two layers, the information threshold remains unchanged but the epidemic threshold can be enhanced, making the contact layer more resilient to epidemic outbreak. We develop a physical theory to understand the intricate interplay between the two types of spreading dynamics.",2014 May 29,"['Wang, Wei', 'Tang, Ming', 'Yang, Hui', 'Younghae Do', 'Lai, Ying-Cheng', 'Lee, GyuWon']",Sci Rep,,,True
f8b28dc077a4d62178940c43350079dd6b0b91bd,PMC,Mesoniviruses are mosquito-specific viruses with extensive geographic distribution and host range,http://dx.doi.org/10.1186/1743-422X-11-97,PMC4038087,24884700,CC BY,"BACKGROUND: The family Mesoniviridae (order Nidovirales) comprises of a group of positive-sense, single-stranded RNA ([+]ssRNA) viruses isolated from mosquitoes. FINDINGS: Thirteen novel insect-specific virus isolates were obtained from mosquitoes collected in Indonesia, Thailand and the USA. By electron microscopy, the virions appeared as spherical particles with a diameter of ~50 nm. Their 20,129 nt to 20,777 nt genomes consist of positive-sense, single-stranded RNA with a poly-A tail. Four isolates from Houston, Texas, and one isolate from Java, Indonesia, were identified as variants of the species Alphamesonivirus-1 which also includes Nam Dinh virus (NDiV) from Vietnam and Cavally virus (CavV) from Côte d’Ivoire. The eight other isolates were identified as variants of three new mesoniviruses, based on genome organization and pairwise evolutionary distances: Karang Sari virus (KSaV) from Java, Bontag Baru virus (BBaV) from Java and Kalimantan, and Kamphaeng Phet virus (KPhV) from Thailand. In comparison with NDiV, the three new mesoniviruses each contained a long insertion (180 – 588 nt) of unknown function in the 5’ region of ORF1a, which accounted for much of the difference in genome size. The insertions contained various short imperfect repeats and may have arisen by recombination or sequence duplication. CONCLUSIONS: In summary, based on their genome organizations and phylogenetic relationships, thirteen new viruses were identified as members of the family Mesoniviridae, order Nidovirales. Species demarcation criteria employed previously for mesoniviruses would place five of these isolates in the same species as NDiV and CavV (Alphamesonivirus-1) and the other eight isolates would represent three new mesonivirus species (Alphamesonivirus-5, Alphamesonivirus-6 and Alphamesonivirus-7). The observed spatiotemporal distribution over widespread geographic regions and broad species host range in mosquitoes suggests that mesoniviruses may be common in mosquito populations worldwide.",2014 May 20,"['Vasilakis, Nikos', 'Guzman, Hilda', 'Firth, Cadhla', 'Forrester, Naomi L', 'Widen, Steven G', 'Wood, Thomas G', 'Rossi, Shannan L', 'Ghedin, Elodie', 'Popov, Vsevolov', 'Blasdell, Kim R', 'Walker, Peter J', 'Tesh, Robert B']",Virol J,,,True
586244c9f0237c8e2ad291d176ec1705a04ddea6,PMC,Mesoniviruses are mosquito-specific viruses with extensive geographic distribution and host range,http://dx.doi.org/10.1186/1743-422X-11-97,PMC4038087,24884700,CC BY,"BACKGROUND: The family Mesoniviridae (order Nidovirales) comprises of a group of positive-sense, single-stranded RNA ([+]ssRNA) viruses isolated from mosquitoes. FINDINGS: Thirteen novel insect-specific virus isolates were obtained from mosquitoes collected in Indonesia, Thailand and the USA. By electron microscopy, the virions appeared as spherical particles with a diameter of ~50 nm. Their 20,129 nt to 20,777 nt genomes consist of positive-sense, single-stranded RNA with a poly-A tail. Four isolates from Houston, Texas, and one isolate from Java, Indonesia, were identified as variants of the species Alphamesonivirus-1 which also includes Nam Dinh virus (NDiV) from Vietnam and Cavally virus (CavV) from Côte d’Ivoire. The eight other isolates were identified as variants of three new mesoniviruses, based on genome organization and pairwise evolutionary distances: Karang Sari virus (KSaV) from Java, Bontag Baru virus (BBaV) from Java and Kalimantan, and Kamphaeng Phet virus (KPhV) from Thailand. In comparison with NDiV, the three new mesoniviruses each contained a long insertion (180 – 588 nt) of unknown function in the 5’ region of ORF1a, which accounted for much of the difference in genome size. The insertions contained various short imperfect repeats and may have arisen by recombination or sequence duplication. CONCLUSIONS: In summary, based on their genome organizations and phylogenetic relationships, thirteen new viruses were identified as members of the family Mesoniviridae, order Nidovirales. Species demarcation criteria employed previously for mesoniviruses would place five of these isolates in the same species as NDiV and CavV (Alphamesonivirus-1) and the other eight isolates would represent three new mesonivirus species (Alphamesonivirus-5, Alphamesonivirus-6 and Alphamesonivirus-7). The observed spatiotemporal distribution over widespread geographic regions and broad species host range in mosquitoes suggests that mesoniviruses may be common in mosquito populations worldwide.",2014 May 20,"['Vasilakis, Nikos', 'Guzman, Hilda', 'Firth, Cadhla', 'Forrester, Naomi L', 'Widen, Steven G', 'Wood, Thomas G', 'Rossi, Shannan L', 'Ghedin, Elodie', 'Popov, Vsevolov', 'Blasdell, Kim R', 'Walker, Peter J', 'Tesh, Robert B']",Virol J,,,False
53c724259063603c2e3676cbce495688151db443,PMC,Mesoniviruses are mosquito-specific viruses with extensive geographic distribution and host range,http://dx.doi.org/10.1186/1743-422X-11-97,PMC4038087,24884700,CC BY,"BACKGROUND: The family Mesoniviridae (order Nidovirales) comprises of a group of positive-sense, single-stranded RNA ([+]ssRNA) viruses isolated from mosquitoes. FINDINGS: Thirteen novel insect-specific virus isolates were obtained from mosquitoes collected in Indonesia, Thailand and the USA. By electron microscopy, the virions appeared as spherical particles with a diameter of ~50 nm. Their 20,129 nt to 20,777 nt genomes consist of positive-sense, single-stranded RNA with a poly-A tail. Four isolates from Houston, Texas, and one isolate from Java, Indonesia, were identified as variants of the species Alphamesonivirus-1 which also includes Nam Dinh virus (NDiV) from Vietnam and Cavally virus (CavV) from Côte d’Ivoire. The eight other isolates were identified as variants of three new mesoniviruses, based on genome organization and pairwise evolutionary distances: Karang Sari virus (KSaV) from Java, Bontag Baru virus (BBaV) from Java and Kalimantan, and Kamphaeng Phet virus (KPhV) from Thailand. In comparison with NDiV, the three new mesoniviruses each contained a long insertion (180 – 588 nt) of unknown function in the 5’ region of ORF1a, which accounted for much of the difference in genome size. The insertions contained various short imperfect repeats and may have arisen by recombination or sequence duplication. CONCLUSIONS: In summary, based on their genome organizations and phylogenetic relationships, thirteen new viruses were identified as members of the family Mesoniviridae, order Nidovirales. Species demarcation criteria employed previously for mesoniviruses would place five of these isolates in the same species as NDiV and CavV (Alphamesonivirus-1) and the other eight isolates would represent three new mesonivirus species (Alphamesonivirus-5, Alphamesonivirus-6 and Alphamesonivirus-7). The observed spatiotemporal distribution over widespread geographic regions and broad species host range in mosquitoes suggests that mesoniviruses may be common in mosquito populations worldwide.",2014 May 20,"['Vasilakis, Nikos', 'Guzman, Hilda', 'Firth, Cadhla', 'Forrester, Naomi L', 'Widen, Steven G', 'Wood, Thomas G', 'Rossi, Shannan L', 'Ghedin, Elodie', 'Popov, Vsevolov', 'Blasdell, Kim R', 'Walker, Peter J', 'Tesh, Robert B']",Virol J,,,False
8781ae40cadd5a251e316e944c0b331e16094f5d,PMC,Mesoniviruses are mosquito-specific viruses with extensive geographic distribution and host range,http://dx.doi.org/10.1186/1743-422X-11-97,PMC4038087,24884700,CC BY,"BACKGROUND: The family Mesoniviridae (order Nidovirales) comprises of a group of positive-sense, single-stranded RNA ([+]ssRNA) viruses isolated from mosquitoes. FINDINGS: Thirteen novel insect-specific virus isolates were obtained from mosquitoes collected in Indonesia, Thailand and the USA. By electron microscopy, the virions appeared as spherical particles with a diameter of ~50 nm. Their 20,129 nt to 20,777 nt genomes consist of positive-sense, single-stranded RNA with a poly-A tail. Four isolates from Houston, Texas, and one isolate from Java, Indonesia, were identified as variants of the species Alphamesonivirus-1 which also includes Nam Dinh virus (NDiV) from Vietnam and Cavally virus (CavV) from Côte d’Ivoire. The eight other isolates were identified as variants of three new mesoniviruses, based on genome organization and pairwise evolutionary distances: Karang Sari virus (KSaV) from Java, Bontag Baru virus (BBaV) from Java and Kalimantan, and Kamphaeng Phet virus (KPhV) from Thailand. In comparison with NDiV, the three new mesoniviruses each contained a long insertion (180 – 588 nt) of unknown function in the 5’ region of ORF1a, which accounted for much of the difference in genome size. The insertions contained various short imperfect repeats and may have arisen by recombination or sequence duplication. CONCLUSIONS: In summary, based on their genome organizations and phylogenetic relationships, thirteen new viruses were identified as members of the family Mesoniviridae, order Nidovirales. Species demarcation criteria employed previously for mesoniviruses would place five of these isolates in the same species as NDiV and CavV (Alphamesonivirus-1) and the other eight isolates would represent three new mesonivirus species (Alphamesonivirus-5, Alphamesonivirus-6 and Alphamesonivirus-7). The observed spatiotemporal distribution over widespread geographic regions and broad species host range in mosquitoes suggests that mesoniviruses may be common in mosquito populations worldwide.",2014 May 20,"['Vasilakis, Nikos', 'Guzman, Hilda', 'Firth, Cadhla', 'Forrester, Naomi L', 'Widen, Steven G', 'Wood, Thomas G', 'Rossi, Shannan L', 'Ghedin, Elodie', 'Popov, Vsevolov', 'Blasdell, Kim R', 'Walker, Peter J', 'Tesh, Robert B']",Virol J,,,False
312f7d52c437036fdc131e828cd4c86ff3886a0e,PMC,Mesoniviruses are mosquito-specific viruses with extensive geographic distribution and host range,http://dx.doi.org/10.1186/1743-422X-11-97,PMC4038087,24884700,CC BY,"BACKGROUND: The family Mesoniviridae (order Nidovirales) comprises of a group of positive-sense, single-stranded RNA ([+]ssRNA) viruses isolated from mosquitoes. FINDINGS: Thirteen novel insect-specific virus isolates were obtained from mosquitoes collected in Indonesia, Thailand and the USA. By electron microscopy, the virions appeared as spherical particles with a diameter of ~50 nm. Their 20,129 nt to 20,777 nt genomes consist of positive-sense, single-stranded RNA with a poly-A tail. Four isolates from Houston, Texas, and one isolate from Java, Indonesia, were identified as variants of the species Alphamesonivirus-1 which also includes Nam Dinh virus (NDiV) from Vietnam and Cavally virus (CavV) from Côte d’Ivoire. The eight other isolates were identified as variants of three new mesoniviruses, based on genome organization and pairwise evolutionary distances: Karang Sari virus (KSaV) from Java, Bontag Baru virus (BBaV) from Java and Kalimantan, and Kamphaeng Phet virus (KPhV) from Thailand. In comparison with NDiV, the three new mesoniviruses each contained a long insertion (180 – 588 nt) of unknown function in the 5’ region of ORF1a, which accounted for much of the difference in genome size. The insertions contained various short imperfect repeats and may have arisen by recombination or sequence duplication. CONCLUSIONS: In summary, based on their genome organizations and phylogenetic relationships, thirteen new viruses were identified as members of the family Mesoniviridae, order Nidovirales. Species demarcation criteria employed previously for mesoniviruses would place five of these isolates in the same species as NDiV and CavV (Alphamesonivirus-1) and the other eight isolates would represent three new mesonivirus species (Alphamesonivirus-5, Alphamesonivirus-6 and Alphamesonivirus-7). The observed spatiotemporal distribution over widespread geographic regions and broad species host range in mosquitoes suggests that mesoniviruses may be common in mosquito populations worldwide.",2014 May 20,"['Vasilakis, Nikos', 'Guzman, Hilda', 'Firth, Cadhla', 'Forrester, Naomi L', 'Widen, Steven G', 'Wood, Thomas G', 'Rossi, Shannan L', 'Ghedin, Elodie', 'Popov, Vsevolov', 'Blasdell, Kim R', 'Walker, Peter J', 'Tesh, Robert B']",Virol J,,,False
28a01c582588f326714549b5f7ba16515175666f,PMC,Mesoniviruses are mosquito-specific viruses with extensive geographic distribution and host range,http://dx.doi.org/10.1186/1743-422X-11-97,PMC4038087,24884700,CC BY,"BACKGROUND: The family Mesoniviridae (order Nidovirales) comprises of a group of positive-sense, single-stranded RNA ([+]ssRNA) viruses isolated from mosquitoes. FINDINGS: Thirteen novel insect-specific virus isolates were obtained from mosquitoes collected in Indonesia, Thailand and the USA. By electron microscopy, the virions appeared as spherical particles with a diameter of ~50 nm. Their 20,129 nt to 20,777 nt genomes consist of positive-sense, single-stranded RNA with a poly-A tail. Four isolates from Houston, Texas, and one isolate from Java, Indonesia, were identified as variants of the species Alphamesonivirus-1 which also includes Nam Dinh virus (NDiV) from Vietnam and Cavally virus (CavV) from Côte d’Ivoire. The eight other isolates were identified as variants of three new mesoniviruses, based on genome organization and pairwise evolutionary distances: Karang Sari virus (KSaV) from Java, Bontag Baru virus (BBaV) from Java and Kalimantan, and Kamphaeng Phet virus (KPhV) from Thailand. In comparison with NDiV, the three new mesoniviruses each contained a long insertion (180 – 588 nt) of unknown function in the 5’ region of ORF1a, which accounted for much of the difference in genome size. The insertions contained various short imperfect repeats and may have arisen by recombination or sequence duplication. CONCLUSIONS: In summary, based on their genome organizations and phylogenetic relationships, thirteen new viruses were identified as members of the family Mesoniviridae, order Nidovirales. Species demarcation criteria employed previously for mesoniviruses would place five of these isolates in the same species as NDiV and CavV (Alphamesonivirus-1) and the other eight isolates would represent three new mesonivirus species (Alphamesonivirus-5, Alphamesonivirus-6 and Alphamesonivirus-7). The observed spatiotemporal distribution over widespread geographic regions and broad species host range in mosquitoes suggests that mesoniviruses may be common in mosquito populations worldwide.",2014 May 20,"['Vasilakis, Nikos', 'Guzman, Hilda', 'Firth, Cadhla', 'Forrester, Naomi L', 'Widen, Steven G', 'Wood, Thomas G', 'Rossi, Shannan L', 'Ghedin, Elodie', 'Popov, Vsevolov', 'Blasdell, Kim R', 'Walker, Peter J', 'Tesh, Robert B']",Virol J,,,False
2ebf1526911eca26db1a7933e592260302caa3b7,PMC,A Novel Universal Neutralizing Monoclonal Antibody against Enterovirus 71 That Targets the Highly Conserved “Knob” Region of VP3 Protein,http://dx.doi.org/10.1371/journal.pntd.0002895,PMC4038473,24875055,CC BY,"Hand, foot and mouth disease caused by enterovirus 71(EV71) leads to the majority of neurological complications and death in young children. While putative inactivated vaccines are only now undergoing clinical trials, no specific treatment options exist yet. Ideally, EV71 specific intravenous immunoglobulins could be developed for targeted treatment of severe cases. To date, only a single universally neutralizing monoclonal antibody against a conserved linear epitope of VP1 has been identified. Other enteroviruses have been shown to possess major conformational neutralizing epitopes on both the VP2 and VP3 capsid proteins. Hence, we attempted to isolate such neutralizing antibodies against conformational epitopes for their potential in the treatment of infection as well as differential diagnosis and vaccine optimization. Here we describe a universal neutralizing monoclonal antibody that recognizes a conserved conformational epitope of EV71 which was mapped using escape mutants. Eight escape mutants from different subgenogroups (A, B2, B4, C2, C4) were rescued; they harbored three essential mutations either at amino acid positions 59, 62 or 67 of the VP3 protein which are all situated in the “knob” region. The escape mutant phenotype could be mimicked by incorporating these mutations into reverse genetically engineered viruses showing that P59L, A62D, A62P and E67D abolish both monoclonal antibody binding and neutralization activity. This is the first conformational neutralization epitope mapped on VP3 for EV71.",2014 May 29,"['Kiener, Tanja K.', 'Jia, Qiang', 'Meng, Tao', 'Chow, Vincent Tak Kwong', 'Kwang, Jimmy']",PLoS Negl Trop Dis,,,True
d0bace106b5562f5e1cf5b124331f9c526d46d21,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,True
6fd2d02aa0a14ee3abc038a93632b9a53231c004,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,False
ffb2127ddb0f8548f3f9a5e2da25a8d716c1dc56,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,False
bf98247f3fce1a28bd9b3eefb26265c83dfb4883,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,False
cccd00693812328980f4652e418319de1d27c455,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,False
8476daf05ad6126ff4f5a6fedee2e3c7b8faecbb,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,False
315d4cc4aa30d30ddab0007ac05b4c817a4617f4,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,False
52dfb9ce5951426c5fb9ad7bf82186038938ab66,PMC,Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts,http://dx.doi.org/10.1371/journal.pgen.1004403,PMC4038475,24875882,CC BY,"Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.",2014 May 29,"['Daugherty, Matthew D.', 'Young, Janet M.', 'Kerns, Julie A.', 'Malik, Harmit S.']",PLoS Genet,,,False
17dbd5741595c1e5b7508063b31147be9263e7f0,PMC,Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus,http://dx.doi.org/10.1371/journal.ppat.1004166,PMC4038610,24874215,CC BY,"Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS–CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.",2014 May 29,"['Lundin, Anna', 'Dijkman, Ronald', 'Bergström, Tomas', 'Kann, Nina', 'Adamiak, Beata', 'Hannoun, Charles', 'Kindler, Eveline', 'Jónsdóttir, Hulda R.', 'Muth, Doreen', 'Kint, Joeri', 'Forlenza, Maria', 'Müller, Marcel A.', 'Drosten, Christian', 'Thiel, Volker', 'Trybala, Edward']",PLoS Pathog,,,True
0899d745009fa75954f75b381c040aebd927832a,PMC,The evolution of disease: anthropological perspectives on epidemiologic transitions,http://dx.doi.org/10.3402/gha.v7.23303,PMC4038768,24848652,CC BY,"BACKGROUND: The model of epidemiologic transitions has served as a guiding framework for understanding relationships between patterns of human health and disease and economic development for the past several decades. However, epidemiologic transition theory is infrequently employed in epidemiology. OBJECTIVE: Moving beyond Omran's original formulation, we discuss critiques and modifications of the theory of epidemiologic transitions and highlight some of the ways in which incorporating epidemiologic transition theory can benefit theory and practice in epidemiology. DESIGN: We focus on two broad contemporary trends in human health that epidemiologic transition theory is useful for conceptualizing: the increased incidence of chronic inflammatory diseases (CIDs), such as allergic and autoimmune diseases, and the emergence and reemergence of infectious disease. RESULTS: Situating these trends within epidemiologic transition theory, we explain the rise in CIDs with the hygiene hypothesis and the rise in emerging and reemerging infections with the concept of a third epidemiologic transition. CONCLUSIONS: Contextualizing these trends within epidemiologic transition theory reveals implications for clinical practice, global health policies, and future research within epidemiology.",2014 May 15,"['Zuckerman, Molly Kathleen', 'Harper, Kristin Nicole', 'Barrett, Ronald', 'Armelagos, George John']",Glob Health Action,,,True
20905ce137d4d5735c25f22352a653f3ebcbc4fc,PMC,Full-Genome Sequence of Human Betacoronavirus 2c Jordan-N3/2012 after Serial Passage in Mammalian Cells,http://dx.doi.org/10.1128/genomeA.00324-14,PMC4038873,24874668,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is the etiologic agent of a highly lethal pneumonia. Here, we report the full-genome sequence of the Jordan-N3/2012 strain after serial passage in two distinct mammalian cell lines. The genome exhibits noteworthy stability, which may inform the development of vaccines and therapeutics used to treat infection with this virus.",2014 May 29,"['Frey, Kenneth G.', 'Redden, Cassie L.', 'Bishop-Lilly, Kimberly A.', 'Johnson, Reed', 'Hensley, Lisa E.', 'Raviprakash, Kanakatte', 'Luke, Thomas', 'Kochel, Tad', 'Mokashi, Vishwesh P.', 'Defang, Gabriel N.']",Genome Announc,,,True
f34cdf2bec51c797567dedf6f00954351ebe5320,PMC,"Genome Sequence of the Novel Reassortant Mammalian Orthoreovirus Strain MRV00304/13, Isolated from a Calf with Diarrhea from the United States",http://dx.doi.org/10.1128/genomeA.00451-14,PMC4038876,24874671,CC BY,"Mammalian orthoreovirus (MRV) strain MRV00304/13 was isolated from diarrheic calves. The serotype-specific antigen σ1 was found to be 95% identical to that of bovine MRV1. All predicted viral proteins had >92% identity to those of MRV except µ2 and σ1s (80 and 72% identities, respectively), suggesting that MRV00304/13 is a novel reassortant MRV1.",2014 May 29,"['Anbalagan, Srivishnupriya', 'Spaans, Tina', 'Hause, Ben M.']",Genome Announc,,,True
59d6529a7cd680c358b3caf56b8517ad61b82aca,PMC,"Complete Genome Sequence of K14JB01, a Novel Variant Strain of Porcine Epidemic Diarrhea Virus in South Korea",http://dx.doi.org/10.1128/genomeA.00505-14,PMC4038887,24874682,CC BY,A novel variant strain of porcine epidemic diarrhea virus (PEDV) emerged on pig farms in South Korea during late 2013. Genomic DNA isolated from a K14JB01 strain identified in a diarrheal pig showed high sequence similarity to PEDV strains prevailing in the United States in 2013. This is the first study to identify the complete genome sequence of a novel variant PEDV in South Korea.,2014 May 29,"['Cho, Yoon-Young', 'Lim, Seong-In', 'Kim, Yong Kwan', 'Song, Jae-Young', 'Lee, Joong-Bok', 'An, Dong-Jun']",Genome Announc,,,True
6bba4b00882498efa69f66a1a92b1c240acfd2a9,PMC,Actinobacillus pleuropneumoniae Possesses an Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1371/journal.pone.0098434,PMC4039538,24878741,CC BY,"Pigs are often colonized by more than one bacterial and/or viral species during respiratory tract infections. This phenomenon is known as the porcine respiratory disease complex (PRDC). Actinobacillus pleuropneumoniae (App) and porcine reproductive and respiratory syndrome virus (PRRSV) are pathogens that are frequently involved in PRDC. The main objective of this project was to study the in vitro interactions between these two pathogens and the host cells in the context of mixed infections. To fulfill this objective, PRRSV permissive cell lines such as MARC-145, SJPL, and porcine alveolar macrophages (PAM) were used. A pre-infection with PRRSV was performed at 0.5 multiplicity of infection (MOI) followed by an infection with App at 10 MOI. Bacterial adherence and cell death were compared. Results showed that PRRSV pre-infection did not affect bacterial adherence to the cells. PRRSV and App co-infection produced an additive cytotoxicity effect. Interestingly, a pre-infection of SJPL and PAM cells with App blocked completely PRRSV infection. Incubation of SJPL and PAM cells with an App cell-free culture supernatant is also sufficient to significantly block PRRSV infection. This antiviral activity is not due to LPS but rather by small molecular weight, heat-resistant App metabolites (<1 kDa). The antiviral activity was also observed in SJPL cells infected with swine influenza virus but to a much lower extent compared to PRRSV. More importantly, the PRRSV antiviral activity of App was also seen with PAM, the cells targeted by the virus in vivo during infection in pigs. The antiviral activity might be due, at least in part, to the production of interferon γ. The use of in vitro experimental models to study viral and bacterial co-infections will lead to a better understanding of the interactions between pathogens and their host cells, and could allow the development of novel prophylactic and therapeutic tools.",2014 May 30,"['Lévesque, Cynthia', 'Provost, Chantale', 'Labrie, Josée', 'Hernandez Reyes, Yenney', 'Burciaga Nava, Jorge A.', 'Gagnon, Carl A.', 'Jacques, Mario']",PLoS One,,,True
b31d9e4a450071584fa87e054414be87264def22,PMC,Vitamin D(3) and gargling for the prevention of upper respiratory tract infections: a randomized controlled trial,http://dx.doi.org/10.1186/1471-2334-14-273,PMC4041358,24885201,CC BY,"BACKGROUND: We undertook a 2X2 factorial, randomized controlled trial (RCT) to assess whether vitamin D(3) supplementation (10,000 international units per week) versus placebo and gargling versus no gargling could prevent viral, clinical upper respiratory tract infection (URTI) in university students. METHODS: We randomized 600 students into 4 treatment arms: 1) vitamin D(3) and gargling, 2) placebo and gargling, 3) vitamin D(3) and no gargling, and 4) placebo and no gargling. Students completed weekly electronic surveys and submitted self-collected mid-turbinate nasal flocked swabs during September and October in 2010 or 2011. Symptomatic students also completed an electronic symptom diary. The primary and secondary outcomes were the occurrence of symptomatic clinical URTI and laboratory confirmed URTI respectively. RESULTS: Of 600 participants, 471 (78.5%) completed all surveys while 43 (7.2%) completed none; 150 (25.0%) reported clinical URTI. Seventy participants (23.3%) randomized to vitamin D(3) reported clinical URTI compared to 80 (26.7%) randomized to placebo (RR:0.79, CI(95):0.61-1.03, p = 0.09). Eighty-five participants (28.3%) randomized to gargling reported clinical URTI compared to 65 participants (21.7%) randomized to the no gargling arm (RR:1.3, CI(95):0.92-1.57, p = 0.19). Laboratory testing identified 70 infections (46.7 per 100 URTIs). Vitamin D(3) treatment was associated with a significantly lower risk for laboratory confirmed URTI (RR: 0.54, CI(95):0.34-0.84, p = 0.007) and with a significantly lower mean viral load measured as log(10) viral copies/mL (mean difference: -0.89, CI(95:) -1.7, -0.06, p = 0.04). Fewer students assigned to gargling experienced laboratory confirmed URTI, however this was not statistically significant (RR:0.82, CI(95):0.53-1.26, p = 0.36). CONCLUSIONS: These results suggest that vitamin D(3) is a promising intervention for the prevention of URTI. Vitamin D(3) significantly reduced the risk of laboratory confirmed URTI and may reduce the risk of clinical infections. TRIAL REGISTRATION: Clinical Trials Registration: NCT01158560.",2014 May 19,"['Goodall, Emma C', 'Granados, Andrea C', 'Luinstra, Kathy', 'Pullenayegum, Eleanor', 'Coleman, Brenda L', 'Loeb, Mark', 'Smieja, Marek']",BMC Infect Dis,,,True
bdd4a8a3507c4df13f06d8693ce8d6b4e9d6c3af,PMC,Identification and genotyping of feline infectious peritonitis-associated single nucleotide polymorphisms in the feline interferon-γ gene,http://dx.doi.org/10.1186/1297-9716-45-57,PMC4041894,24886103,CC BY,"Feline infectious peritonitis (FIP) is an immune-mediated, highly lethal disease caused by feline coronavirus (FCoV) infection. Currently, no protective vaccine or effective treatment for the disease is available. Studies have found that some cats survive the challenge of virulent FCoV isolates. Since cellular immunity is thought to be critical in preventing FIP and because diseased cats often show a significant decrease in interferon-γ (IFN-γ) production, we investigated whether single nucleotide polymorphisms (SNP) in the feline IFN-γ gene (fIFNG) are associated with the outcome of infection. A total of 82 asymptomatic and 63 FIP cats were analyzed, and 16 SNP were identified in intron 1 of fIFNG. Among these SNP, the fFING + 428 T allele was shown to be a FIP-resistant allele (p = 0.03), and the heterozygous genotypes 01C/T and +408C/T were found to be FIP-susceptible factors (p = 0.004). Furthermore, an fIFNG + 428 resistant allele also showed a clear correlation with the plasma level of IFN-γ in FIP cats. For the identification of these three FIP-related SNP, genotyping methods were established using amplification refractory mutation system PCR (ARMS-PCR) and restriction fragment length polymorphisms (RFLP), and the different genotypes could easily be identified without sequencing. The identification of additional FIP-related SNP will allow the selection of resistant cats and decrease the morbidity of the cat population to FIP.",2014 May 21,"['Hsieh, Li-En', 'Chueh, Ling-Ling']",Vet Res,,,True
ab2859ea36cc85687a9caad282ffaca666bd0b64,PMC,A highly conserved WDYPKCDRA epitope in the RNA directed RNA polymerase of human coronaviruses can be used as epitope-based universal vaccine design,http://dx.doi.org/10.1186/1471-2105-15-161,PMC4041900,24884408,CC BY,"BACKGROUND: Coronaviruses are the diverse group of RNA virus. From 1960, six strains of human coronaviruses have emerged that includes SARS-CoV and the recent infection by deadly MERS-CoV which is now going to cause another outbreak. Prevention of these viruses is urgent and a universal vaccine for all strain could be a promising solution in this circumstance. In this study we aimed to design an epitope based vaccine against all strain of human coronavirus. RESULTS: Multiple sequence alignment (MSA) approach was employed among spike (S), membrane (M), enveloped (E) and nucleocapsid (N) protein and replicase polyprotein 1ab to identify which one is highly conserve in all coronaviruses strains. Next, we use various in silico tools to predict consensus immunogenic and conserved peptide. We found that conserved region is present only in the RNA directed RNA polymerase protein. In this protein we identified one epitope WDYPKCDRA is highly immunogenic and 100% conserved among all available human coronavirus strains. CONCLUSIONS: Here we suggest in vivo study of our identified novel peptide antigen in RNA directed RNA polymerase protein for universal vaccine – which may be the way to prevent all human coronavirus disease.",2014 May 29,"['Sharmin, Refat', 'Islam, Abul Bashar Mir Md Khademul']",BMC Bioinformatics,,,True
3d2fae37d61a2e45cf0dff9bc0abee361bbf9a8d,PMC,Polypeptide N-acetylgalactosaminyltransferase 2 regulates cellular metastasis-associated behavior in gastric cancer,http://dx.doi.org/10.3892/ijmm.2012.1130,PMC4042861,22992780,CC BY,"Aberrant glycosylation of cell surface glycoprotein due to specific alterations of glycosyltransferase activity is usually associated with invasion and metastasis of cancer, particularly of gastric carcinomas. Polypeptide N-acetylgalactosaminyltransferase 2 (ppGalNAc-T2), which catalyzes initiation of mucin-type O-glycosylation, is also involved in tumor migration and invasion. However, a comprehensive understanding of how ppGalNAc-T2 correlates with the metastasic potential of human gastric cancer is not currently available. In the present study, ppGalNAc-T2 was detected in a variety of human poorly differentiated tumor cells, and expression appeared to be higher in SGC7901 gastric cancer cells. In addition, we investigated the potential effects of ppGalNAc-T2 on growth and metastasis-associated behavior in SGC7901 cells after stable transfection with ppGalNAc-T2 sense and antisense vectors. We found that cell proliferation, adhesion and invasion were decreased in ppGalNAc-T2 overexpressed cells but increased in ppGalNAc-T2 downregulated cells. Therefore, we attempted to clarify the mechanisms underlying the anti-metastatic activities of ppGalNAc-T2. Further investigation indicated that overexpression of ppGalNAc-T2 is involved in the inhibition of matrix metalloproteinase (MMP)-2 expression at both the protein and mRNA levels, which may be associated with ppGalNAc-T2 suppressing the expression of transforming growth factor (TGF)-β1. However, it did not exhibit any apparent correlation with MMP-14 expression levels. Our data show the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901 gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferative and anti-metastatic activity through the decrease of MMP-2 and TGF-β1. These results indicate that ppGalNAc-T2 may be used as a novel therapeutic target for human gastric cancer treatment.",2012 Dec 18,"['HUA, DONG', 'SHEN, LI', 'XU, LAN', 'JIANG, ZHI', 'ZHOU, YINGHUI', 'YUE, AIHUAN', 'ZOU, SHITAO', 'CHENG, ZHIHONG', 'WU, SHILIANG']",Int J Mol Med,,,True
98936f4aa8ad9759352811bbb4aa531c2f061cd7,PMC,Inhibitory effect of sodium houttuyfonate on synovial proliferation in vitro in cells from a patient with rheumatoid arthritis,http://dx.doi.org/10.3892/etm.2014.1636,PMC4043587,24926358,CC BY,"The aim of the present study was to investigate the inhibitory effect of sodium houttuyfonate (SH) on synovial cell proliferation in vitro. Primary cells were obtained from the synovial tissue of a patient with rheumatoid arthritis (RA). The cells were divided into five treatment groups as follows: the control group (group 1), 25 μg/ml SH-treated group (group 2), 50 μg/ml SH-treated group (group 3), 100 μg/ml SH-treated group (group 4) and the 200 μg/ml SH-treated group (group 5). Following seven days of treatment, the proliferation rate of the synovial cells was then detected using an MTT assay. The expression level of proliferative synovial cells markedly decreased in the SH-treated groups in a dose-dependent manner compared with the control group. In conclusion, the present study demonstrated that SH was able to inhibit the proliferation of synovial cells obtained from a patient with RA. These results provide a potential theoretical basis for the development of a safe and effective treatment against RA in the future.",2014 Jun 27,"['LI, JUN', 'ZHOU, TING', 'ZHAO, FUTAO']",Exp Ther Med,,,True
5eb1e53fb44c8a997713bd4fc55d65b904df3ce8,PMC,Silver Sucrose Octasulfate (IASOS™) as a Valid Active Ingredient into a Novel Vaginal Gel against Human Vaginal Pathogens: In Vitro Antimicrobial Activity Assessment,http://dx.doi.org/10.1371/journal.pone.0097791,PMC4045761,24897299,CC BY,"This in vitro study assessed the antimicrobial properties of a novel octasilver salt of Sucrose Octasulfate (IASOS) as well as of an innovative vaginal gel containing IASOS (SilSOS Femme), against bacterial and yeast pathogens isolated from human clinical cases of symptomatic vaginal infections. In BHI and LAPT culture media, different ionic silver concentrations and different pHs were tested. IASOS exerted a strong antimicrobial activity towards all the pathogens tested in both culture media. The results demonstrated that salts and organic compounds present in the culture media influenced IASOS efficacy only to a moderate extent. Whereas comparable MBCs (Minimal Bactericidal Concentrations) were observed for G. vaginalis (10 mg/L Ag(+)), E. coli and E. aerogenes (25 mg/L Ag(+)) in both media, higher MBCs were found for S. aureus and S. agalactiae in LAPT cultures (50 mg/L Ag(+) versus 25 mg/L Ag(+)). No minimal concentration totally inhibiting the growth of C. albicans was found. Nevertheless, in both media at the highest ionic silver concentrations (50–200 mg/L Ag(+)), a significant 34–52% drop in Candida growth was observed. pH differently affected the antimicrobial properties of IASOS against bacteria or yeasts; however, a stronger antimicrobial activity at pH higher than the physiological pH was generally observed. It can be therefore concluded that IASOS exerts a bactericidal action against all the tested bacteria and a clear fungistatic action against C. albicans. The antimicrobial activity of the whole vaginal gel SilSOS Femme further confirmed the antimicrobial activity of IASOS. Overall, our findings support IASOS as a valid active ingredient into a vaginal gel.",2014 Jun 4,"['Marianelli, Cinzia', 'Petrucci, Paola', 'Comelli, Maria Cristina', 'Calderini, Gabriella']",PLoS One,,,True
4c4214329dbbf291d7c73b5afb2a145559f780e2,PMC,Decreased expression of eukaryotic initiation factor 3f is an adverse prognostic factor for stage I–III gastric cancer,http://dx.doi.org/10.1186/1477-7819-12-72,PMC4046624,24678890,CC BY,"BACKGROUND: It has been demonstrated that eIF3f expression is significantly decreased in many human cancers, a fact which plays an important role in human cancer. However, the expression of eIF3f in gastric cancer (GC) is not well understood to date. Therefore, the aim of this study is to detect the expression of eIF3f in GC. METHODS: The expression of eIF3f was examined by immunohistochemistry in tissues with stage I to III GC and adjacent non-cancerous tissues (ANCT) of 195 gastrectomy specimens; clinicopathological results, including survival, were analyzed. RESULTS: The positive expression rate of eIF3f was significantly higher in ANCT tissues than in GC. eIF3f levels were correlated with more advanced tumor stages and likelihood of recurrence (all P <0.05). The Kaplan-Meier survival curves indicated that decreased expression of eIF3f could serve as a prognosis marker for poor outcome of GC patients (P = 0.04). CONCLUSIONS: eIF3f may play an important role in recurrence, thus representing a promising predictive marker for the prognosis of GC.",2014 Mar 28,"['Li, Guanghua', 'Wang, Na', 'Sun, Chuanjin', 'Li, Bo']",World J Surg Oncol,,,True
38aa050ad79d8a1d7022c33535255ce9d47914e5,PMC,Potent Inhibition of Junín Virus Infection by Interferon in Murine Cells,http://dx.doi.org/10.1371/journal.pntd.0002933,PMC4046933,24901990,CC BY,"The new world arenavirus Junín virus (JUNV) is the causative agent of Argentine hemorrhagic fever, a lethal human infectious disease. Adult laboratory mice are generally resistant to peripheral infection by JUNV. The mechanism underlying the mouse resistance to JUNV infection is largely unknown. We have reported that interferon receptor knockout mice succumb to JUNV infection, indicating the critical role of interferon in restricting JUNV infection in mice. Here we report that the pathogenic and vaccine strains of JUNV were highly sensitive to interferon in murine primary cells. Treatment with low concentrations of interferon abrogated viral NP protein expression in murine cells. The replication of both JUNVs was enhanced in IRF3/IRF7 deficient cells. In addition, the vaccine strain of JUNV displayed impaired growth in primary murine cells. Our data suggested a direct and potent role of host interferon response in restricting JUNV replication in mice. The defect in viral growth for vaccine JUNV might also partially explain its attenuation in mice.",2014 Jun 5,"['Huang, Cheng', 'Walker, Aida G.', 'Grant, Ashley M.', 'Kolokoltsova, Olga A.', 'Yun, Nadezhda E.', 'Seregin, Alexey V.', 'Paessler, Slobodan']",PLoS Negl Trop Dis,,,True
0326bf875d2a22d7c4a4328dcd34c2d801fd110e,PMC,Neglected Zoonotic Diseases—The Long and Winding Road to Advocacy,http://dx.doi.org/10.1371/journal.pntd.0002800,PMC4046968,24901769,CC BY,"BACKGROUND: Years of advocacy for the neglected tropical diseases (NTDs) have focused the world's attention on these diseases of the poor, resulting most recently in the 2012 “London Declaration” and the recent World Health Assembly Resolution WHA66.12 on NTDs in May 2013. Control of the endemic neglected zoonotic diseases (NZDs) would benefit from a similar campaign, which needs the support of a global community. METHODOLOGY/PRINCIPAL FINDINGS: The resolutions from all 66 World Health Assembly (WHA) meetings held between 1948 and 2013 were examined to determine how many contain a specific focus on any of the following eight NZDs as defined by the World Health Organisation (WHO): anthrax, bovine tuberculosis (TB), brucellosis, Taenia solium cysticercosis, cystic echinococcosis (hydatidosis), leishmaniasis, rabies, and zoonotic human African trypanosomiasis (HAT or sleeping sickness). Twenty-one resolutions adopted in the 16 assemblies between 1948 and 2013 targeted one or more of these eight NZDs, representing 4% of the total resolutions on infectious diseases passed to date. The 2013 adoption of Resolution WHA66.12 targeting all 17 NTDs marks a change in approach by the WHA. Whereas previous resolutions have targeted the NTDs as separate entities, the new approach of the combined resolution will help increase the overall momentum to target these ancient diseases as coendemic clusters in endemic countries. However, three major NZDs remain outside this recent resolution: anthrax, brucellosis, and bovine TB. CONCLUSIONS AND SIGNIFICANCE: The recent adoption of a specific resolution at the WHA in 2013 that emphasises a One Health approach for the successful control of 17 NTDs is a major development in advocacy. However, recognition of the importance of three major NZDs to public health in endemic countries—anthrax, brucellosis, and bovine tuberculosis—is still lacking despite being prioritised by the WHA as early as the 1950s. Global advocacy for control of the NZDs as a whole would similarly benefit from adoption of a One Health approach as is promoted for the NTDs under WHA66.12.",2014 Jun 5,"['Mableson, Hayley E.', 'Okello, Anna', 'Picozzi, Kim', 'Welburn, Susan Christina']",PLoS Negl Trop Dis,,,True
1b248ec38c2c12737c005fd38db1bec556675707,PMC,A Loss of Function Analysis of Host Factors Influencing Vaccinia virus Replication by RNA Interference,http://dx.doi.org/10.1371/journal.pone.0098431,PMC4047015,24901222,CC BY,"Vaccinia virus (VACV) is a large, cytoplasmic, double-stranded DNA virus that requires complex interactions with host proteins in order to replicate. To explore these interactions a functional high throughput small interfering RNA (siRNA) screen targeting 6719 druggable cellular genes was undertaken to identify host factors (HF) influencing the replication and spread of an eGFP-tagged VACV. The experimental design incorporated a low multiplicity of infection, thereby enhancing detection of cellular proteins involved in cell-to-cell spread of VACV. The screen revealed 153 pro- and 149 anti-viral HFs that strongly influenced VACV replication. These HFs were investigated further by comparisons with transcriptional profiling data sets and HFs identified in RNAi screens of other viruses. In addition, functional and pathway analysis of the entire screen was carried out to highlight cellular mechanisms involved in VACV replication. This revealed, as anticipated, that many pro-viral HFs are involved in translation of mRNA and, unexpectedly, suggested that a range of proteins involved in cellular transcriptional processes and several DNA repair pathways possess anti-viral activity. Multiple components of the AMPK complex were found to act as pro-viral HFs, while several septins, a group of highly conserved GTP binding proteins with a role in sequestering intracellular bacteria, were identified as strong anti-viral VACV HFs. This screen has identified novel and previously unexplored roles for cellular factors in poxvirus replication. This advancement in our understanding of the VACV life cycle provides a reliable knowledge base for the improvement of poxvirus-based vaccine vectors and development of anti-viral theraputics.",2014 Jun 5,"['Beard, Philippa M.', 'Griffiths, Samantha J.', 'Gonzalez, Orland', 'Haga, Ismar R.', 'Pechenick Jowers, Tali', 'Reynolds, Danielle K.', 'Wildenhain, Jan', 'Tekotte, Hille', 'Auer, Manfred', 'Tyers, Mike', 'Ghazal, Peter', 'Zimmer, Ralf', 'Haas, Jürgen']",PLoS One,,,True
10dd2aeb61d54b45337a96f3c6243b72d6764732,PMC,Using HIV Networks to Inform Real Time Prevention Interventions,http://dx.doi.org/10.1371/journal.pone.0098443,PMC4047027,24901437,CC0,"OBJECTIVE: To reconstruct the local HIV-1 transmission network from 1996 to 2011 and use network data to evaluate and guide efforts to interrupt transmission. DESIGN: HIV-1 pol sequence data were analyzed to infer the local transmission network. METHODS: We analyzed HIV-1 pol sequence data to infer a partial local transmission network among 478 recently HIV-1 infected persons and 170 of their sexual and social contacts in San Diego, California. A transmission network score (TNS) was developed to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner and target prevention interventions. RESULTS: HIV-1 pol sequences from 339 individuals (52.3%) were highly similar to sequences from at least one other participant (i.e., clustered). A high TNS (top 25%) was significantly correlated with baseline risk behaviors (number of unique sexual partners and insertive unprotected anal intercourse (p = 0.014 and p = 0.0455, respectively) and predicted risk of transmission (p<0.0001). Retrospective analysis of antiretroviral therapy (ART) use, and simulations of ART targeted to individuals with the highest TNS, showed significantly reduced network level HIV transmission (p<0.05). CONCLUSIONS: Sequence data from an HIV-1 screening program focused on recently infected persons and their social and sexual contacts enabled the characterization of a highly connected transmission network. The network-based risk score (TNS) was highly correlated with transmission risk behaviors and outcomes, and can be used identify and target effective prevention interventions, like ART, to those at a greater risk for HIV-1 transmission.",2014 Jun 5,"['Little, Susan J.', 'Kosakovsky Pond, Sergei L.', 'Anderson, Christy M.', 'Young, Jason A.', 'Wertheim, Joel O.', 'Mehta, Sanjay R.', 'May, Susanne', 'Smith, Davey M.']",PLoS One,,,True
a4995af42a012dd1b7f8da3936d79d78d0e24405,PMC,Interactome Profile of the Host Cellular Proteins and the Nonstructural Protein 2 of Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1371/journal.pone.0099176,PMC4047090,24901321,CC BY,"The nonstructural protein 2 (NSP2) is considered to be one of crucial viral proteins in the replication and pathogenesis of porcine reproductive and respiratory syndrome virus (PRRSV). In the present study, the host cellular proteins that interact with the NSP2 of PRRSV were immunoprecipitated with anti-Myc antibody from the MARC-145 cells infected by a recombinant PRRSV with 3xMyc tag insertion in its NSP2-coding region, and then 285 cellular proteins interacting with NSP2 were identified by LC-MS/MS. The Gene Ontology and enriched KEGG Pathway bioinformatics analyses indicated that the identified proteins could be assigned to different subcellular locations and functional classes. Functional analysis of the interactome profile highlighted cellular pathways associated with infectious disease, translation, immune system, nervous system and signal transduction. Two interested cellular proteins–BCL2-associated athanogene 6 (BAG6) and apoptosis-inducing factor 1 (AIF1) which may involve in transporting of NSP2 to Endoplasmic reticulum (ER) or PRRSV-driven apoptosis were validated by Western blot. The interactome data between PRRSV NSP2 and cellular proteins contribute to the understanding of the roles of NSP2 in the replication and pathogenesis of PRRSV, and also provide novel cellular target proteins for elucidating the associated molecular mechanisms of the interaction of host cellular proteins with viral proteins in regulating the viral replication.",2014 Jun 5,"['Wang, Li', 'Zhou, Lei', 'Zhang, Han', 'Li, Yan', 'Ge, Xinna', 'Guo, Xin', 'Yu, Kangzhen', 'Yang, Hanchun']",PLoS One,,,True
2557b13f557e15081960d49034d890a790943b38,PMC,Nonstructural Protein 5A Is Incorporated into Hepatitis C Virus Low-Density Particle through Interaction with Core Protein and Microtubules during Intracellular Transport,http://dx.doi.org/10.1371/journal.pone.0099022,PMC4048239,24905011,CC BY,"Nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) serves dual functions in viral RNA replication and virus assembly. Here, we demonstrate that HCV replication complex along with NS5A and Core protein was transported to the lipid droplet (LD) through microtubules, and NS5A-Core complexes were then transported from LD through early-to-late endosomes to the plasma membrane via microtubules. Further studies by cofractionation analysis and immunoelectron microscopy of the released particles showed that NS5A-Core complexes, but not NS4B, were present in the low-density fractions, but not in the high-density fractions, of the HCV RNA-containing virions and associated with the internal virion core. Furthermore, exosomal markers CD63 and CD81 were also detected in the low-density fractions, but not in the high-density fractions. Overall, our results suggest that HCV NS5A is associated with the core of the low-density virus particles which exit the cell through a preexisting endosome/exosome pathway and may contribute to HCV natural infection.",2014 Jun 6,"['Lai, Chao-Kuen', 'Saxena, Vikas', 'Tseng, Chung-Hsin', 'Jeng, King-Song', 'Kohara, Michinori', 'Lai, Michael M. C.']",PLoS One,,,True
60d68e4052a397966e72c6eda0895ca7d27afb68,PMC,Improving rheumatic fever surveillance in New Zealand: results of a surveillance sector review,http://dx.doi.org/10.1186/1471-2458-14-528,PMC4049392,24885018,CC BY,"BACKGROUND: The New Zealand (NZ) Government has made a strong commitment to reduce the incidence of rheumatic fever (RF) by two thirds, to 1.4 cases per 100,000, by mid-2017. We reviewed the NZ RF surveillance sector, aiming to identify potential improvements which would support optimal RF control and prevention activities. METHODS: This review used a recently developed surveillance sector review method. Interviews with 36 key informants were used to describe the sector, assess it and identify its gaps. Priorities for improvement and implementation strategies were determined following discussion with these key informants, with policy advisors and within the research team. RESULTS: Key improvements identified included the need for a comprehensive RF surveillance strategy, integrated reporting and an online national RF register. At a managerial level this review provided evidence for system change and built support for this across the surveillance sector. CONCLUSIONS: The surveillance sector review approach can be added to the small set of tools currently available for developing and evaluating surveillance systems. This new approach is likely to prove useful as we confront the challenges of combating new emerging infectious diseases, responding to global environmental changes, and reducing health inequalities.",2014 May 29,"['Oliver, Jane', 'Pierse, Nevil', 'Baker, Michael G']",BMC Public Health,,,True
bab3e74b5db5b2e04b521d1172b9df7726871aaa,PMC,Core Self-Evaluations Mediate the Associations of Dispositional Optimism and Life Satisfaction,http://dx.doi.org/10.1371/journal.pone.0097752,PMC4049581,24911367,CC BY,"BACKGROUND: Positive traits, such as life satisfaction, optimism, and core self-evaluation (CSE), have garnered increasing attention from researchers and professionals. However, the trilateral relationship among them remains unclear. OBJECTIVE: This study examines the effect of dispositional optimism on life satisfaction and primarily verified the mediator role of CSEs. METHODS: Six hundred thirty college students from two general universities completed a questionnaire packet containing life orientation test–revised (LOT–R), core self-evaluations, and satisfaction with life scale. Confirmatory factor analysis (CFA) was conducted to assess the dimension of LOT–R. Bootstrap was used in structural equation modeling to analyze mediation effect. RESULTS: Results revealed that dispositional optimism and core self-evaluations were significantly correlated with life satisfaction. CFA identified the bidimensional structure of dispositional optimism. SEM indicated that core self-evaluations partially mediated the effect of dispositional optimism on life satisfaction. The final model also revealed significant paths from optimism and pessimism to life satisfaction through core-self evaluations. CONCLUSION: The findings extended prior studies and shed light on how dispositional optimism influences life satisfaction. This study provides valuable evidence on how to promote the life satisfaction of human beings in positive psychology. A further study can fully explore the relationship among them in multi-cultural follow-up studies.",2014 Jun 9,"['Jiang, Wensheng', 'Li, Fei', 'Jiang, Haipeng', 'Yu, Lili', 'Liu, Wenbo', 'Li, Qiang', 'Zuo, Luning']",PLoS One,,,True
fbf214b2ff7bf5dc3d5dab6096d53cb086f0dea4,PMC,Estimated Effects of Projected Climate Change on the Basic Reproductive Number of the Lyme Disease Vector Ixodes scapularis,http://dx.doi.org/10.1289/ehp.1307799,PMC4050516,24627295,CC0,"Background: The extent to which climate change may affect human health by increasing risk from vector-borne diseases has been under considerable debate. Objectives: We quantified potential effects of future climate change on the basic reproduction number (R(0)) of the tick vector of Lyme disease, Ixodes scapularis, and explored their importance for Lyme disease risk, and for vector-borne diseases in general. Methods: We applied observed temperature data for North America and projected temperatures using regional climate models to drive an I. scapularis population model to hindcast recent, and project future, effects of climate warming on R(0). Modeled R(0) increases were compared with R(0) ranges for pathogens and parasites associated with variations in key ecological and epidemiological factors (obtained by literature review) to assess their epidemiological importance. Results: R(0) for I. scapularis in North America increased during the years 1971–2010 in spatio-temporal patterns consistent with observations. Increased temperatures due to projected climate change increased R(0) by factors (2–5 times in Canada and 1.5–2 times in the United States), comparable to observed ranges of R(0) for pathogens and parasites due to variations in strains, geographic locations, epidemics, host and vector densities, and control efforts. Conclusions: Climate warming may have co-driven the emergence of Lyme disease in northeastern North America, and in the future may drive substantial disease spread into new geographic regions and increase tick-borne disease risk where climate is currently suitable. Our findings highlight the potential for climate change to have profound effects on vectors and vector-borne diseases, and the need to refocus efforts to understand these effects. Citation: Ogden NH, Radojević M, Wu X, Duvvuri VR, Leighton PA, Wu J. 2014. Estimated effects of projected climate change on the basic reproductive number of the Lyme disease vector Ixodes scapularis. Environ Health Perspect 122:631–638; http://dx.doi.org/10.1289/ehp.1307799",2014 Jun 14,"['Ogden, Nicholas H.', 'Radojevic´, Milka', 'Wu, Xiaotian', 'Duvvuri, Venkata R.', 'Leighton, Patrick A.', 'Wu, Jianhong']",Environ Health Perspect,,,True
feccc27dc3c4100c8080abda883969ec979956c9,PMC,Estimated Effects of Projected Climate Change on the Basic Reproductive Number of the Lyme Disease Vector Ixodes scapularis,http://dx.doi.org/10.1289/ehp.1307799,PMC4050516,24627295,CC0,"Background: The extent to which climate change may affect human health by increasing risk from vector-borne diseases has been under considerable debate. Objectives: We quantified potential effects of future climate change on the basic reproduction number (R(0)) of the tick vector of Lyme disease, Ixodes scapularis, and explored their importance for Lyme disease risk, and for vector-borne diseases in general. Methods: We applied observed temperature data for North America and projected temperatures using regional climate models to drive an I. scapularis population model to hindcast recent, and project future, effects of climate warming on R(0). Modeled R(0) increases were compared with R(0) ranges for pathogens and parasites associated with variations in key ecological and epidemiological factors (obtained by literature review) to assess their epidemiological importance. Results: R(0) for I. scapularis in North America increased during the years 1971–2010 in spatio-temporal patterns consistent with observations. Increased temperatures due to projected climate change increased R(0) by factors (2–5 times in Canada and 1.5–2 times in the United States), comparable to observed ranges of R(0) for pathogens and parasites due to variations in strains, geographic locations, epidemics, host and vector densities, and control efforts. Conclusions: Climate warming may have co-driven the emergence of Lyme disease in northeastern North America, and in the future may drive substantial disease spread into new geographic regions and increase tick-borne disease risk where climate is currently suitable. Our findings highlight the potential for climate change to have profound effects on vectors and vector-borne diseases, and the need to refocus efforts to understand these effects. Citation: Ogden NH, Radojević M, Wu X, Duvvuri VR, Leighton PA, Wu J. 2014. Estimated effects of projected climate change on the basic reproductive number of the Lyme disease vector Ixodes scapularis. Environ Health Perspect 122:631–638; http://dx.doi.org/10.1289/ehp.1307799",2014 Jun 14,"['Ogden, Nicholas H.', 'Radojevic´, Milka', 'Wu, Xiaotian', 'Duvvuri, Venkata R.', 'Leighton, Patrick A.', 'Wu, Jianhong']",Environ Health Perspect,,,True
f719d2ff295ade18c5946296cd7c2436727d2822,PMC,Structural and functional characterization of MERS coronavirus papain-like protease,http://dx.doi.org/10.1186/1423-0127-21-54,PMC4051379,24898546,CC BY,"BACKGROUNDS: A new highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and Saudi Arabia and quickly spread to some European countries since September 2012. Until 15 May 2014, it has infected at least 572 people with a fatality rate of about 30% globally. Studies to understand the virus and to develop antiviral drugs or therapy are necessary and urgent. In the present study, MERS-CoV papain-like protease (PL(pro)) is expressed, and its structural and functional consequences are elucidated. RESULTS: Circular dichroism and Tyr/Trp fluorescence analyses indicated that the secondary and tertiary structure of MERS-CoV PL(pro) is well organized and folded. Analytical ultracentrifugation analyses demonstrated that MERS-CoV PL(pro) is a monomer in solution. The steady-state kinetic and deubiquitination activity assays indicated that MERS-CoV PL(pro) exhibits potent deubiquitination activity but lower proteolytic activity, compared with SARS-CoV PL(pro). A natural mutation, Leu105, is the major reason for this difference. CONCLUSIONS: Overall, MERS-CoV PL(pro) bound by an endogenous metal ion shows a folded structure and potent proteolytic and deubiquitination activity. These findings provide important insights into the structural and functional properties of coronaviral PL(pro) family, which is applicable to develop strategies inhibiting PL(pro) against highly pathogenic coronaviruses.",2014 Jun 4,"['Lin, Min-Han', 'Chuang, Shang-Ju', 'Chen, Chiao-Che', 'Cheng, Shu-Chun', 'Cheng, Kai-Wen', 'Lin, Chao-Hsiung', 'Sun, Chiao-Yin', 'Chou, Chi-Yuan']",J Biomed Sci,,,True
5a1718b5f9e6b1d39eab3363e7d49678ef87f1f9,PMC,Structural and functional characterization of MERS coronavirus papain-like protease,http://dx.doi.org/10.1186/1423-0127-21-54,PMC4051379,24898546,CC BY,"BACKGROUNDS: A new highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and Saudi Arabia and quickly spread to some European countries since September 2012. Until 15 May 2014, it has infected at least 572 people with a fatality rate of about 30% globally. Studies to understand the virus and to develop antiviral drugs or therapy are necessary and urgent. In the present study, MERS-CoV papain-like protease (PL(pro)) is expressed, and its structural and functional consequences are elucidated. RESULTS: Circular dichroism and Tyr/Trp fluorescence analyses indicated that the secondary and tertiary structure of MERS-CoV PL(pro) is well organized and folded. Analytical ultracentrifugation analyses demonstrated that MERS-CoV PL(pro) is a monomer in solution. The steady-state kinetic and deubiquitination activity assays indicated that MERS-CoV PL(pro) exhibits potent deubiquitination activity but lower proteolytic activity, compared with SARS-CoV PL(pro). A natural mutation, Leu105, is the major reason for this difference. CONCLUSIONS: Overall, MERS-CoV PL(pro) bound by an endogenous metal ion shows a folded structure and potent proteolytic and deubiquitination activity. These findings provide important insights into the structural and functional properties of coronaviral PL(pro) family, which is applicable to develop strategies inhibiting PL(pro) against highly pathogenic coronaviruses.",2014 Jun 4,"['Lin, Min-Han', 'Chuang, Shang-Ju', 'Chen, Chiao-Che', 'Cheng, Shu-Chun', 'Cheng, Kai-Wen', 'Lin, Chao-Hsiung', 'Sun, Chiao-Yin', 'Chou, Chi-Yuan']",J Biomed Sci,,,False
08885e2da682c5d027e986aacc166975e01fc60c,PMC,Lung ultrasound imaging in avian influenza A (H7N9) respiratory failure,http://dx.doi.org/10.1186/2036-7902-6-6,PMC4051407,24949191,CC BY,"BACKGROUND: Lung ultrasound has been shown to identify in real-time, various pathologies of the lung such as pneumonia, viral pneumonia, and acute respiratory distress syndrome (ARDS). Lung ultrasound maybe a first-line alternative to chest X-ray and CT scan in critically ill patients with respiratory failure. We describe the use of lung ultrasound imaging and findings in two cases of severe respiratory failure from avian influenza A (H7N9) infection. METHODS: Serial lung ultrasound images and video from two cases of H7N9 respiratory failure requiring mechanical ventilation and extracorporeal membrane oxygenation in a tertiary care intensive care unit were analyzed for characteristic lung ultrasound findings described previously for respiratory failure and infection. These findings were followed serially, correlated with clinical course and chest X-ray. RESULTS: In both patients, characteristic lung ultrasound findings have been observed as previously described in viral pulmonary infections: subpleural consolidations associated or not with local pleural effusion. In addition, numerous, confluent, or coalescing B-lines leading to ‘white lung’ with corresponding pleural line thickening are associated with ARDS. Extension or reduction of lesions observed with ultrasound was also correlated respectively with clinical worsening or improvement. Coexisting consolidated pneumonia with sonographic air bronchograms was noted in one patient who did not survive. CONCLUSIONS: Clinicians with access to point-of-care ultrasonography may use these findings as an alternative to chest X-ray or CT scan. Lung ultrasound imaging may assist in the efficient allocation of intensive care for patients with respiratory failure from viral pulmonary infections, especially in resource scarce settings or situations such as future respiratory virus outbreaks or pandemics.",2014 May 20,"['Tsai, Nga Wing', 'Ngai, Chun Wai', 'Mok, Ka Leung', 'Tsung, James W']",Crit Ultrasound J,,,True
6aa7ff7bbaba12fef375a84c5ba297d9f848541f,PMC,"NGS Nominated CELA1, HSPG2, and KCNK5 as Candidate Genes for Predisposition to Balkan Endemic Nephropathy",http://dx.doi.org/10.1155/2014/920723,PMC4052113,24949484,CC BY,"Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression leading to terminal renal failure. The results of molecular biological investigations propose that BEN is a multifactorial disease with genetic predisposition to environmental risk agents. Exome sequencing of 22 000 genes with Illumina Nextera Exome Enrichment Kit was performed on 22 DNA samples (11 Bulgarian patients and 11 Serbian patients). Software analysis was performed via NextGene, Provean, and PolyPhen. The frequency of all annotated genetic variants with deleterious/damaging effect was compared with those of European populations. Then we focused on nonannotated variants (with no data available about them and not found in healthy Bulgarian controls). There is no statistically significant difference between annotated variants in BEN patients and European populations. From nonannotated variants with more than 40% frequency in both patients' groups, we nominated 3 genes with possible deleterious/damaging variants—CELA1, HSPG2, and KCNK5. Mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN.",2014 May 15,"['Toncheva, D.', 'Mihailova-Hristova, M.', 'Vazharova, R.', 'Staneva, R.', 'Karachanak, S.', 'Dimitrov, P.', 'Simeonov, V.', 'Ivanov, S.', 'Balabanski, L.', 'Serbezov, D.', 'Malinov, M.', 'Stefanovic, V.', 'Čukuranović, R.', 'Polenakovic, M.', 'Jankovic-Velickovic, L.', 'Djordjevic, V.', 'Jevtovic-Stoimenov, T.', 'Plaseska-Karanfilska, D.', 'Galabov, A.', 'Djonov, V.', 'Dimova, I.']",Biomed Res Int,,,True
bdd49a68f33046aa3a724721b7050c5f548f90de,PMC,Identification of Plakortide E from the Caribbean Sponge Plakortis halichondroides as a Trypanocidal Protease Inhibitor using Bioactivity-Guided Fractionation,http://dx.doi.org/10.3390/md12052614,PMC4052307,24798927,CC BY,"In this paper, we report new protease inhibitory activity of plakortide E towards cathepsins and cathepsin-like parasitic proteases. We further report on its anti-parasitic activity against Trypanosoma brucei with an IC(50) value of 5 μM and without cytotoxic effects against J774.1 macrophages at 100 μM concentration. Plakortide E was isolated from the sponge Plakortis halichondroides using enzyme assay-guided fractionation and identified by NMR spectroscopy and mass spectrometry. Furthermore, enzyme kinetic studies confirmed plakortide E as a non-competitive, slowly-binding, reversible inhibitor of rhodesain.",2014 May 2,"['Oli, Swarna', 'Abdelmohsen, Usama Ramadan', 'Hentschel, Ute', 'Schirmeister, Tanja']",Mar Drugs,,,True
a81118016cd86948665a49c7562f577f83cb87b5,PMC,"Response surface modeling for hot, humid air decontamination of materials contaminated with Bacillus anthracis ∆Sterne and Bacillus thuringiensis Al Hakam spores",http://dx.doi.org/10.1186/s13568-014-0021-3,PMC4052701,24949256,CC BY,"Response surface methodology using a face-centered cube design was used to describe and predict spore inactivation of Bacillus anthracis ∆Sterne and Bacillus thuringiensis Al Hakam spores after exposure of six spore-contaminated materials to hot, humid air. For each strain/material pair, an attempt was made to fit a first or second order model. All three independent predictor variables (temperature, relative humidity, and time) were significant in the models except that time was not significant for B. thuringiensis Al Hakam on nylon. Modeling was unsuccessful for wiring insulation and wet spores because there was complete spore inactivation in the majority of the experimental space. In cases where a predictive equation could be fit, response surface plots with time set to four days were generated. The survival of highly purified Bacillus spores can be predicted for most materials tested when given the settings for temperature, relative humidity, and time. These predictions were cross-checked with spore inactivation measurements.",2014 May 1,"['Prokop, Edward J', 'Crigler, John R', 'Wells, Claire M', 'Young, Alice A', 'Buhr, Tony L']",AMB Express,,,True
bc1d2578b23ef87c23e94bb11bf4986606483527,PMC,Conflicts of Interest during Contact Investigations: A Game-Theoretic Analysis,http://dx.doi.org/10.1155/2014/952381,PMC4052784,24982688,CC BY,"The goal of contact tracing is to reduce the likelihood of transmission, particularly to individuals who are at greatest risk for developing complications of infection, as well as identifying individuals who are in need of medical treatment of other interventions. In this paper, we develop a simple mathematical model of contact investigations among a small group of individuals and apply game theory to explore conflicts of interest that may arise in the context of perceived costs of disclosure. Using analytic Kolmogorov equations, we determine whether or not it is possible for individual incentives to drive noncooperation, even though cooperation would yield a better group outcome. We found that if all individuals have a cost of disclosure, then the optimal individual decision is to simply not disclose each other. With further analysis of (1) completely offsetting the costs of disclosure and (2) partially offsetting the costs of disclosure, we found that all individuals disclose all contacts, resulting in a smaller basic reproductive number and an alignment of individual and group optimality. More data are needed to understand decision making during outbreak investigations and what the real and perceived costs are.",2014 Apr 14,"['Sippl-Swezey, Nicolas', 'Enanoria, Wayne T.', 'Porco, Travis C.']",Comput Math Methods Med,,,True
ce6af0bb9b796bf3ddc44ddabdce04a7584957d5,PMC,Antiviral activity and possible mode of action of ellagic acid identified in Lagerstroemia speciosa leaves toward human rhinoviruses,http://dx.doi.org/10.1186/1472-6882-14-171,PMC4052798,24885569,CC BY,"BACKGROUND: Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cause billions of USD annually in medical visits and school and work absenteeism. An assessment was made of the cytotoxic and antiviral activities and possible mode of action of the tannin ellagic acid from the leaves of Lagerstroemia speciosa toward HeLa cells and three rhinoviruses, HRV-2, -3, and -4. METHODS: The antiviral property and mechanism of action of ellagic acid were evaluated using a sulforhodamine B assay and real-time reverse transcription-PCR (RT-PCR) with SYBR Green dye. Results were compared with those of the currently used broad-spectrum antiviral agent, ribavirin. RESULTS: As judged by 50% inhibitory concentration values, natural ellagic acid was 1.8, 2.3, and 2.2 times more toxic toward HRV-2 (38 μg/mL), HRV-3 (31 μg/mL), and HRV-4 (29 μg/mL) than ribavirin, respectively. The inhibition rate of preincubation with 50 μg/mL ellagic acid was 17%, whereas continuous presence of ellagic acid during infection led to a significant increase in the inhibition (70%). Treatment with 50 μg/mL ellagic acid considerably suppressed HRV-4 infection only when added just after the virus inoculation (0 h) (87% inhibition), but not before -1 h or after 1 h or later (<20% inhibition). These findings suggest that ellagic acid does not interact with the HRV-4 particles and may directly interact with the human cells in the early stage of HRV infections to protect the cells from the virus destruction. Furthermore, RT-PCR analysis revealed that 50 μg/mL ellagic acid strongly inhibited the RNA replication of HRV-4 in HeLa cells, suggesting that ellagic acid inhibits virus replication by targeting on cellular molecules, rather than virus molecules. CONCLUSIONS: Global efforts to reduce the level of antibiotics justify further studies on L. speciosa leaf-derived materials containing ellagic acid as potential anti-HRV products or a lead molecule for the prevention or treatment of HRV infection.",2014 May 26,"['Park, Sang Wook', 'Kwon, Min Jung', 'Yoo, Ji Young', 'Choi, Hwa-Jung', 'Ahn, Young-Joon']",BMC Complement Altern Med,,,True
fdf03dcd427aa029a6b213288a7e862519decafb,PMC,Glycyrrhizic Acid in the Treatment of Liver Diseases: Literature Review,http://dx.doi.org/10.1155/2014/872139,PMC4052927,24963489,CC BY,"Glycyrrhizic acid (GA) is a triterpene glycoside found in the roots of licorice plants (Glycyrrhiza glabra). GA is the most important active ingredient in the licorice root, and possesses a wide range of pharmacological and biological activities. GA coupled with glycyrrhetinic acid and 18-beta-glycyrrhetic acid was developed in China or Japan as an anti-inflammatory, antiviral, and antiallergic drug for liver disease. This review summarizes the current biological activities of GA and its medical applications in liver diseases. The pharmacological actions of GA include inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects. This paper will be a useful reference for physicians and biologists researching GA and will open the door to novel agents in drug discovery and development from Chinese herbs. With additional research, GA may be more widely used in the treatment of liver diseases or other conditions.",2014 May 13,"['Li, Jian-yuan', 'Cao, Hong-yan', 'Liu, Ping', 'Cheng, Gen-hong', 'Sun, Ming-yu']",Biomed Res Int,,,True
c42f9e96fcbb25a8f456fb17af3d591c1300ae64,PMC,RIG-I Enhanced Interferon Independent Apoptosis upon Junin Virus Infection,http://dx.doi.org/10.1371/journal.pone.0099610,PMC4053358,24918927,CC BY,"Junin virus (JUNV) is the etiological agent of Argentine hemorrhagic fever (AHF), a human disease with a high case-fatality rate. It is widely accepted that arenaviral infections, including JUNV infections, are generally non-cytopathic. In contrast, here we demonstrated apoptosis induction in human lung epithelial carcinoma (A549), human hepatocarcinoma and Vero cells upon infection with the attenuated Candid#1 strain of, JUNV as determined by phosphatidylserine (PS) translocation, Caspase 3 (CASP3) activation, Poly (ADP-ribose) polymerase (PARP) cleavage and/or chromosomal DNA fragmentation. Moreover, as determined by DNA fragmentation, we found that the pathogenic Romero strain of JUNV was less cytopathic than Candid#1 in human hepatocarcinoma and Vero, but more apoptotic in A549 and Vero E6 cells. Additionally, we found that JUNV-induced apoptosis was enhanced by RIG-I signaling. Consistent with the previously reported role of RIG-I like helicase (RLH) signaling in initiating programmed cell death, we showed that cell death or DNA fragmentation of Candid#1-infected A549 cells was decreased upon siRNA or shRNA silencing of components of RIG-I pathway in spite of increased virus production. Similarly, we observed decreased DNA fragmentation in JUNV-infected human hepatocarcinoma cells deficient for RIG-I when compared with that of RIG-I-competent cells. In addition, DNA fragmentation detected upon Candid#1 infection of type I interferon (IFN)-deficient Vero cells suggested a type I IFN-independent mechanism of apoptosis induction in response to JUNV. Our work demonstrated for the first time apoptosis induction in various cells of mammalian origin in response to JUNV infection and partial mechanism of this cell death.",2014 Jun 11,"['Kolokoltsova, Olga A.', 'Grant, Ashley M.', 'Huang, Cheng', 'Smith, Jennifer K.', 'Poussard, Allison L.', 'Tian, Bing', 'Brasier, Allan R.', 'Peters, Clarence J.', 'Tseng, Chien-Te Kent', 'de la Torre, Juan C.', 'Paessler, Slobodan']",PLoS One,,,True
f9075b3b2fcb919dd92b981ac6161302c5f904cd,PMC,Targeting IL-1β and IL-17A Driven Inflammation during Influenza-Induced Exacerbations of Chronic Lung Inflammation,http://dx.doi.org/10.1371/journal.pone.0098440,PMC4053370,24918427,CC BY,"For patients with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), exacerbations are life-threatening events causing acute respiratory distress that can even lead to hospitalization and death. Although a great deal of effort has been put into research of exacerbations and potential treatment options, the exact underlying mechanisms are yet to be deciphered and no therapy that effectively targets the excessive inflammation is available. In this study, we report that interleukin-1β (IL-1β) and interleukin-17A (IL-17A) are key mediators of neutrophilic inflammation in influenza-induced exacerbations of chronic lung inflammation. Using a mouse model of disease, our data shows a role for IL-1β in mediating lung dysfunction, and in driving neutrophilic inflammation during the whole phase of viral infection. We further report a role for IL-17A as a mediator of IL-1β induced neutrophilia at early time points during influenza-induced exacerbations. Blocking of IL-17A or IL-1 resulted in a significant abrogation of neutrophil recruitment to the airways in the initial phase of infection or at the peak of viral replication, respectively. Therefore, IL-17A and IL-1β are potential targets for therapeutic treatment of viral exacerbations of chronic lung inflammation",2014 Jun 11,"['Sichelstiel, Anke', 'Yadava, Koshika', 'Trompette, Aurélien', 'Salami, Olawale', 'Iwakura, Yoichiro', 'Nicod, Laurent P.', 'Marsland, Benjamin J.']",PLoS One,,,True
63f9ef8701b8b68aab585d81fa58bd567ade8e4a,PMC,Critical role of cellular cholesterol in bovine rotavirus infection,http://dx.doi.org/10.1186/1743-422X-11-98,PMC4053397,24884772,CC BY,"BACKGROUND: Bovine rotavirus (BRV) is a non-enveloped dsRNA virus that cause neonatal calf diarrhea. Lipid rafts are cholesterol-enrich membrane mircodomains that play a vital role in many cellular processes. In this study, the effect of cellular cholesterol depletion on infection of MA-104 cells with bovine rotavirus was investigated. RESULTS: We demonstrated that cholesterol depletion of the plasma membrane by MβCD had no effect on BRV binding to cells but significantly impaired BRV entry in a dose-dependent manner and the effect was partially reversed by addition of exogenous cholesterol, suggesting the reduction of BRV infection by MβCD was specifically due to cholesterol depletion. Cholesterol depletion after virus entry did not reduce BRV replication, whereas affected virus assembly. CONCLUSIONS: Taken together, our results demonstrate that cell membrane cholesterol is essential to BRV infectivity.",2014 May 23,"['Cui, Jin', 'Fu, Xinliang', 'Xie, Jiexiong', 'Gao, Ming', 'Hong, Malin', 'Chen, Yao', 'Su, Shuo', 'Li, Shoujun']",Virol J,,,True
76e0bd45995e7799e0f52be915f66719e24265a9,PMC,Pharmacokinetics of Anti-HBV Polyoxometalate in Rats,http://dx.doi.org/10.1371/journal.pone.0098292,PMC4055585,24921932,CC BY,"Polyoxometalates are non-nucleoside analogs that have been proven to exhibit broad-spectrum antiviral activity. In particular, Cs(2)K(4)Na[SiW(9)Nb(3)O(40)].H(2)O 1 shows low toxicity and high activity against HBV. The preclinical pharmacokinetics of Compound 1 in rats were characterized by establishing and applying inductively coupled plasma-mass spectrometry method to determine the concentration of W in plasma, urine, feces, bile and organ samples. The quantitative ICP-MS method demonstrated good sensitivity and application in the pharmacokinetics study of polyoxometalates. The pharmacokinetic behavior of Compound 1 after intravenous or oral administration fit a two-compartment model. T(max) ranges from 0.1 h to 3 h and the T(1/2) of Compound 1 is between 20 h and 30 h. The absolute bioavailability of Compound 1 at 45, 180 and 720 mg/kg groups were 23.68%, 14.67% and 11.93%, respectively. The rates of plasma protein binding of Compound 1 at 9, 18 and 36 mg/ml of Compound 1 are 62.13±9.41%, 71.20±24.98% and 49.00±25.59%, respectively. Compound 1 was widely distributed throughout the body, and high levels of compound 1 were found in the kidney and liver. The level of Compound 1 in excretion was lower: 30% for urine, 0.28% for feces and 0.42% for bile, respectively. For elaborate pharmacokinetic characteristics to be fully understood, the metabolism of Compound 1 needs to be studied further.",2014 Jun 12,"['Wang, Juan', 'Qu, Xiaofeng', 'Qi, Yanfei', 'Li, Jinhua', 'Song, Xiuling', 'Li, Li', 'Yin, Dehui', 'Xu, Kun', 'Li, Juan']",PLoS One,,,True
d400825a1ea10fb8d5bdbc96b2c00e866eb75f1d,PMC,Equine Arteritis Virus Does Not Induce Interferon Production in Equine Endothelial Cells: Identification of Nonstructural Protein 1 as a Main Interferon Antagonist,http://dx.doi.org/10.1155/2014/420658,PMC4055586,24967365,CC BY,"The objective of this study was to investigate the effect of equine arteritis virus (EAV) on type I interferon (IFN) production. Equine endothelial cells (EECs) were infected with the virulent Bucyrus strain (VBS) of EAV and expression of IFN-β was measured at mRNA and protein levels by quantitative real-time RT-PCR and IFN bioassay using vesicular stomatitis virus expressing the green fluorescence protein (VSV-GFP), respectively. Quantitative RT-PCR results showed that IFN-β mRNA levels in EECs infected with EAV VBS were not increased compared to those in mock-infected cells. Consistent with quantitative RT-PCR, Sendai virus- (SeV-) induced type I IFN production was inhibited by EAV infection. Using an IFN-β promoter-luciferase reporter assay, we subsequently demonstrated that EAV nsps 1, 2, and 11 had the capability to inhibit type I IFN activation. Of these three nsps, nsp1 exhibited the strongest inhibitory effect. Taken together, these data demonstrate that EAV has the ability to suppress the type I IFN production in EECs and nsp1 may play a critical role to subvert the equine innate immune response.",2014 May 25,"['Go, Yun Young', 'Li, Yanhua', 'Chen, Zhenhai', 'Han, Mingyuan', 'Yoo, Dongwan', 'Fang, Ying', 'Balasuriya, Udeni B. R.']",Biomed Res Int,,,True
daa3f7d4838adebf0aac1be3cda2924fc1d2106a,PMC,Circulating Levels of Tumor Necrosis Factor-Alpha Receptor 2 Are Increased in Heart Failure with Preserved Ejection Fraction Relative to Heart Failure with Reduced Ejection Fraction: Evidence for a Divergence in Pathophysiology,http://dx.doi.org/10.1371/journal.pone.0099495,PMC4055721,24923671,CC BY,"BACKGROUND: Various pathways have been implicated in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFPEF). Inflammation in response to comorbid conditions, such as hypertension and diabetes, may play a proportionally larger role in HFPEF as compared to HF with reduced ejection fraction (HFREF). METHODS AND RESULTS: This study investigated inflammation mediated by the tumor necrosis factor-alpha (TNFα) axis in community-based cohorts of HFPEF patients (n = 100), HFREF patients (n = 100) and healthy controls (n = 50). Enzyme-linked immunosorbent assays were used to investigate levels of TNFα, its two receptors (TNFR1 and TNFR2), and a non-TNFα cytokine, interleukin-6 (IL-6), in plasma derived from peripheral blood samples. Plasma levels of TNFα and TNFR1 were significantly elevated in HFPEF relative to controls, while levels of TNFR2 were significantly higher in HFPEF than both controls and HFREF. TNFα, TNFR1 and TNFR2 were each significantly associated with at least two of the following: age, estimated glomerular filtration rate, hypertension, diabetes, smoking, peripheral vascular disease or history of atrial fibrillation. TNFR2 levels were also significantly associated with increasing grade of diastolic dysfunction and severity of symptoms in HFPEF. CONCLUSIONS: Inflammation mediated through TNFα and its receptors, TNFR1 and TNFR2, may represent an important component of a comorbidity-induced inflammatory response that partially drives the pathophysiology of HFPEF.",2014 Jun 12,"['Putko, Brendan N.', 'Wang, Zuocheng', 'Lo, Jennifer', 'Anderson, Todd', 'Becher, Harald', 'Dyck, Jason R. B.', 'Kassiri, Zamaneh', 'Oudit, Gavin Y.', None]",PLoS One,,,True
4cd3f43501d49e775838473a3edafb55e57d08df,PMC,Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1004192,PMC4055766,24945244,CC BY,"Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype often cause severe pneumonia and multiple organ failure in humans, with reported case fatality rates of more than 60%. To develop a clinical antibody therapy, we generated a human-mouse chimeric monoclonal antibody (MAb) ch61 that showed strong neutralizing activity against H5N1 HPAI viruses isolated from humans and evaluated its protective potential in mouse and nonhuman primate models of H5N1 HPAI virus infections. Passive immunization with MAb ch61 one day before or after challenge with a lethal dose of the virus completely protected mice, and partial protection was achieved when mice were treated 3 days after the challenge. In a cynomolgus macaque model, reduced viral loads and partial protection against lethal infection were observed in macaques treated with MAb ch61 intravenously one and three days after challenge. Protective effects were also noted in macaques under immunosuppression. Though mutant viruses escaping from neutralization by MAb ch61 were recovered from macaques treated with this MAb alone, combined treatment with MAb ch61 and peramivir reduced the emergence of escape mutants. Our results indicate that antibody therapy might be beneficial in reducing viral loads and delaying disease progression during H5N1 HPAI virus infection in clinical cases and combined treatment with other antiviral compounds should improve the protective effects of antibody therapy against H5N1 HPAI virus infection.",2014 Jun 12,"['Itoh, Yasushi', 'Yoshida, Reiko', 'Shichinohe, Shintaro', 'Higuchi, Megumi', 'Ishigaki, Hirohito', 'Nakayama, Misako', 'Pham, Van Loi', 'Ishida, Hideaki', 'Kitano, Mitsutaka', 'Arikata, Masahiko', 'Kitagawa, Naoko', 'Mitsuishi, Yachiyo', 'Ogasawara, Kazumasa', 'Tsuchiya, Hideaki', 'Hiono, Takahiro', 'Okamatsu, Masatoshi', 'Sakoda, Yoshihiro', 'Kida, Hiroshi', 'Ito, Mutsumi', 'Quynh Mai, Le', 'Kawaoka, Yoshihiro', 'Miyamoto, Hiroko', 'Ishijima, Mari', 'Igarashi, Manabu', 'Suzuki, Yasuhiko', 'Takada, Ayato']",PLoS Pathog,,,True
f82005e7a19bb8a9a23d6d2d4ce3b5dd18c7d26e,PMC,Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1004192,PMC4055766,24945244,CC BY,"Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype often cause severe pneumonia and multiple organ failure in humans, with reported case fatality rates of more than 60%. To develop a clinical antibody therapy, we generated a human-mouse chimeric monoclonal antibody (MAb) ch61 that showed strong neutralizing activity against H5N1 HPAI viruses isolated from humans and evaluated its protective potential in mouse and nonhuman primate models of H5N1 HPAI virus infections. Passive immunization with MAb ch61 one day before or after challenge with a lethal dose of the virus completely protected mice, and partial protection was achieved when mice were treated 3 days after the challenge. In a cynomolgus macaque model, reduced viral loads and partial protection against lethal infection were observed in macaques treated with MAb ch61 intravenously one and three days after challenge. Protective effects were also noted in macaques under immunosuppression. Though mutant viruses escaping from neutralization by MAb ch61 were recovered from macaques treated with this MAb alone, combined treatment with MAb ch61 and peramivir reduced the emergence of escape mutants. Our results indicate that antibody therapy might be beneficial in reducing viral loads and delaying disease progression during H5N1 HPAI virus infection in clinical cases and combined treatment with other antiviral compounds should improve the protective effects of antibody therapy against H5N1 HPAI virus infection.",2014 Jun 12,"['Itoh, Yasushi', 'Yoshida, Reiko', 'Shichinohe, Shintaro', 'Higuchi, Megumi', 'Ishigaki, Hirohito', 'Nakayama, Misako', 'Pham, Van Loi', 'Ishida, Hideaki', 'Kitano, Mitsutaka', 'Arikata, Masahiko', 'Kitagawa, Naoko', 'Mitsuishi, Yachiyo', 'Ogasawara, Kazumasa', 'Tsuchiya, Hideaki', 'Hiono, Takahiro', 'Okamatsu, Masatoshi', 'Sakoda, Yoshihiro', 'Kida, Hiroshi', 'Ito, Mutsumi', 'Quynh Mai, Le', 'Kawaoka, Yoshihiro', 'Miyamoto, Hiroko', 'Ishijima, Mari', 'Igarashi, Manabu', 'Suzuki, Yasuhiko', 'Takada, Ayato']",PLoS Pathog,,,False
049d30dbc331c7fd67ee83bed3990804272155b0,PMC,Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1004192,PMC4055766,24945244,CC BY,"Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype often cause severe pneumonia and multiple organ failure in humans, with reported case fatality rates of more than 60%. To develop a clinical antibody therapy, we generated a human-mouse chimeric monoclonal antibody (MAb) ch61 that showed strong neutralizing activity against H5N1 HPAI viruses isolated from humans and evaluated its protective potential in mouse and nonhuman primate models of H5N1 HPAI virus infections. Passive immunization with MAb ch61 one day before or after challenge with a lethal dose of the virus completely protected mice, and partial protection was achieved when mice were treated 3 days after the challenge. In a cynomolgus macaque model, reduced viral loads and partial protection against lethal infection were observed in macaques treated with MAb ch61 intravenously one and three days after challenge. Protective effects were also noted in macaques under immunosuppression. Though mutant viruses escaping from neutralization by MAb ch61 were recovered from macaques treated with this MAb alone, combined treatment with MAb ch61 and peramivir reduced the emergence of escape mutants. Our results indicate that antibody therapy might be beneficial in reducing viral loads and delaying disease progression during H5N1 HPAI virus infection in clinical cases and combined treatment with other antiviral compounds should improve the protective effects of antibody therapy against H5N1 HPAI virus infection.",2014 Jun 12,"['Itoh, Yasushi', 'Yoshida, Reiko', 'Shichinohe, Shintaro', 'Higuchi, Megumi', 'Ishigaki, Hirohito', 'Nakayama, Misako', 'Pham, Van Loi', 'Ishida, Hideaki', 'Kitano, Mitsutaka', 'Arikata, Masahiko', 'Kitagawa, Naoko', 'Mitsuishi, Yachiyo', 'Ogasawara, Kazumasa', 'Tsuchiya, Hideaki', 'Hiono, Takahiro', 'Okamatsu, Masatoshi', 'Sakoda, Yoshihiro', 'Kida, Hiroshi', 'Ito, Mutsumi', 'Quynh Mai, Le', 'Kawaoka, Yoshihiro', 'Miyamoto, Hiroko', 'Ishijima, Mari', 'Igarashi, Manabu', 'Suzuki, Yasuhiko', 'Takada, Ayato']",PLoS Pathog,,,False
9e102fc4487f4b9cdc7f7426ad24ba33aa1a4d42,PMC,Immune derangement occurs in patients with H7N9 avian influenza,http://dx.doi.org/10.1186/cc13788,PMC4056113,25030090,CC BY,"INTRODUCTION: Currently, little is known about the immunological characteristics of patients with avian influenza A (H7N9) virus infection. METHODS: The numbers and percentages of peripheral blood immune cells were measured in 27 patients with laboratory-confirmed H7N9 virus infection and 30 healthy controls (HCs). The functional phenotypes of T cells and monocytes, as well as serum cytokine levels, were analyzed by flow cytometry. RESULTS: There were 19 patients (70.4%) with acute respiratory distress syndrome, 13 (48.1%) with secondary respiratory infection, 20 (74%) with systemic inflammatory response syndrome (SIRS; defined as having at least two concurrent SIRS components), 18 (66.7%) with lymphocytopenia and 11 (40.7%) with reduced numbers of monocytes. In comparison with levels in the HCs, the levels of serum interleukin 6 (IL-6), IL-8 and IL-10 and the percentages of CD38+ or Tim-3+ T cells were significantly increased. However, the percentages of human leukocyte antigen-DR + and Tim-3+ monocytes were significantly decreased in patients compared with HCs. CONCLUSIONS: Patients with avian H7N9 virus infection display profound SIRS concomitantly with an anti-inflammatory response, which may be associated with the rapid progression of and high mortality associated with this novel viral disease.",2014 Mar 24,"['Wu, Wei', 'Shi, Yu', 'Gao, Hainv', 'Liang, Weifeng', 'Sheng, Jifang', 'Li, Lanjuan']",Crit Care,,,True
f6d6d7efc1686a7d219ecfc55f9a48ce72d4fb00,PMC,Genome Sequences of Porcine Epidemic Diarrhea Virus: In Vivo and In Vitro Phenotypes,http://dx.doi.org/10.1128/genomeA.00503-14,PMC4056290,24926047,CC BY,"Since the outbreak of porcine epidemic diarrhea virus (PEDV) in May 2013, U.S. swine producers have lost almost five million baby pigs. In an attempt to understand the evolution of PEDV in the United States and possibly develop a control strategy, we compared the genome sequences of a PEDV strain isolated from an infected piglet against its in vitro adapted version. The original PEDV strain was grown in Vero cells and passed 10 times serially in a MARC145 cell line. The sequence analysis of the native PEDV strain and in vitro passaged virus shows that the cell culture adaptation specifically modifies PEDV spike protein whereas the open reading frame 1a/b (ORF1a/b)-encoded polyprotein, the nucleoprotein, NS3B (ORF3), and membrane and envelope proteins remain unchanged.",2014 Jun 12,"['Lawrence, Paulraj K.', 'Bumgardner, Eric', 'Bey, Russell F.', 'Stine, Douglas', 'Bumgarner, Roger E.']",Genome Announc,,,True
6ebb0d128a1f03635f662f5419927c90c61855e5,PMC,Activation of JNK1/2 and p38 MAPK signaling pathways promotes enterovirus 71 infection in immature dendritic cells,http://dx.doi.org/10.1186/1471-2180-14-147,PMC4057572,24906853,CC BY,"BACKGROUND: c-Jun NH(2)-terminal kinase/stress-activated kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase (p38 MAPK) are important components of cellular signal transduction pathways, which have been reported to be involved in viral replication. However, little is known about JNK1/2 and p38 MAPK signaling pathways in enterovirus 71 (EV71)-infected immature dendritic cells (iDCs). Thus, iDCs were induced from peripheral blood mononuclear cells (PBMC) and performed to explore the expressions and phosphorylation of molecules in the two signaling pathways as well as secretions of inflammatory cytokines and interferons during EV71 replication. RESULTS: We showed that EV71 infection could activate both JNK1/2 and p38 MAPK in iDCs and phosphorylate their downstream transcription factors c-Fos and c-Jun, which further promoted the production of IL-2, IL-6, IL-10, and TNF-α. Moreover, EV71 infection also increased the release of IFN-β and IL-12 p40. Pretreatment of iDCs with SP600125 and SB203580 (20 μM) could severely impair viral replication and its induced phosphorylation of JNK1/2,p38 MAPK, c-Fos and c-Jun. In addition, treatment of EV71-infected iDCs with SP600125 and SB203580 could inhibit secretions of IL-6, IL-10 and TNF-α. CONCLUSION: JNK1/2 and p38 MAPK signaling pathways are beneficial to EV71 infection and positively regulate secretions of inflammatory cytokines in iDCs.",2014 Jun 7,"['Peng, Hongjun', 'Shi, Mei', 'Zhang, Li', 'Li, Yuanyuan', 'Sun, Jing', 'Zhang, Lirong', 'Wang, Xiaohui', 'Xu, Xiaopeng', 'Zhang, Xiaolei', 'Mao, Yijie', 'Ji, Yun', 'Jiang, Jingting', 'Shi, Weifeng']",BMC Microbiol,,,True
55f79ab7db345d29089af0c330d95292350ba225,PMC,Influenza and other respiratory virus infections in outpatients with medically attended acute respiratory infection during the 2011-12 influenza season,http://dx.doi.org/10.1111/irv.12247,PMC4057994,24852890,CC BY,"BACKGROUND: Respiratory tract infections are a major cause of outpatient visits, yet only a portion is tested to determine the etiologic organism. Multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) assays for detection of multiple viruses are being used increasingly in clinical settings. METHODS: During January–April 2012, outpatients with acute respiratory illness (≤7 days) were tested for influenza using singleplex RT-PCR (SRT-PCR). A subset was assayed for 18 viruses using MRT-PCR to compare detection of influenza and examine the distribution of viruses and characteristics of patients using multinomial logistic regression. RESULTS: Among 662 participants (6 months–82 years), detection of influenza was similar between the MRT-PCR and SRT-PCR (κ = 0·83). No virus was identified in 267 (40.3%) samples. Commonly detected viruses were human rhinovirus (HRV, 15·4%), coronavirus (CoV, 10·4%), respiratory syncytial virus (RSV, 8·4%), human metapneumovirus (hMPV, 8·3%), and influenza (6%). Co-detections were infrequent (6·9%) and most commonly occurred among those <18 years old. In regression analyses, compared with non-viral illnesses, RSV and hMPV were significantly more frequent in children and less frequent in 18- to 49-year-olds than in those ≥50 years (P = 0·01), fever was more common in hMPV and influenza infections (P = 0·008), nasal congestion was more frequent in CoV, HRV, hMPV, influenza and RSV infections (P = 0·001), and body mass index was higher among those with influenza (P = 0·036). CONCLUSIONS: Using MRT-PCR, a viral etiology was found in three-fifths of patients with medically attended outpatient visits for acute respiratory illness during the influenza season; co-detected viruses were infrequent. Symptoms varied by viral etiology.",2014 Jul 8,"['Zimmerman, Richard K', 'Rinaldo, Charles R', 'Nowalk, Mary Patricia', 'GK, Balasubramani', 'Thompson, Mark G', 'Moehling, Krissy K', 'Bullotta, Arlene', 'Wisniewski, Stephen']",Influenza Other Respir Viruses,,,True
93f8a441807d1356ad516a8681e14fc093ab016b,PMC,Methods To Identify Aptamers against Cell Surface Biomarkers,http://dx.doi.org/10.3390/ph4091216,PMC4058655,,CC BY,"Aptamers are nucleic acid-based ligands identified through a process of molecular evolution named SELEX (Systematic Evolution of Ligands by Exponential enrichment). During the last 10-15 years, numerous aptamers have been developed specifically against targets present on or associated with the surface of human cells or infectious pathogens such as viruses, bacteria, fungi or parasites. Several of the aptamers have been described as potent probes, rivalling antibodies, for use in flow cytometry or microscopy. Some have also been used as drugs by inhibiting or activating functions of their targets in a manner similar to neutralizing or agonistic antibodies. Additionally, it is straightforward to conjugate aptamers to other agents without losing their affinity and they have successfully been used in vitro and in vivo to deliver drugs, siRNA, nanoparticles or contrast agents to target cells. Hence, aptamers identified against cell surface biomarkers represent a promising class of ligands. This review presents the different strategies of SELEX that have been developed to identify aptamers for cell surface-associated proteins as well as some of the methods that are used to study their binding on living cells.",2011 Sep 19,"['Cibiel, Agnes', 'Dupont, Daniel Miotto', 'Ducongé, Frédéric']",Pharmaceuticals (Basel),,,True
9d16d9dcd360578447fca314b4f8b873b23acf0b,PMC,Echinacea—A Source of Potent Antivirals for Respiratory Virus Infections,http://dx.doi.org/10.3390/ph4071019,PMC4058675,,CC BY,"Extracts of Echinacea species have been used traditionally in North America for the control of symptoms of colds, influenza, and other diseases, and some of them have become very popular as “herbal medicines”. Recent studies have revealed that preparations derived from certain species and plant parts, but not all of them, possess potent antiviral activities, at non-cytotoxic concentrations, particularly against membrane-containing viruses. Thus all strains of human and avian influenza viruses tested (including a Tamiflu-resistant strain), as well as herpes simplex virus, respiratory syncytial virus, and rhinoviruses, were very sensitive to a standardized Echinacea purpurea preparation. In mechanistic studies the influenza virus-specific hemagglutinin and neuraminidase were inhibited. In addition some extracts displayed anti-inflammatory activity in virus-infected cells, and numerous other effects on the expression of cellular genes. Multiple components, either discrete compounds or mixtures, appeared to be responsible for the various antiviral activities.",2011 Jul 13,"['Hudson, James', 'Vimalanathan, Selvarani']",Pharmaceuticals (Basel),,,True
a65d8f4193a3b03c5d20fac1972e0756ecf2d328,PMC,Clinical Disease Severity of Respiratory Viral Co-Infection versus Single Viral Infection: A Systematic Review and Meta-Analysis,http://dx.doi.org/10.1371/journal.pone.0099392,PMC4059637,24932493,CC BY,"BACKGROUND: Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections. METHODS: We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses. RESULTS: Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) −0.20 days, 95% CI −0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p<0.001) with viral co-infection as compared to other age groups (I(2) for subgroup analysis 64%, p = 0.04). CONCLUSIONS: No differences in clinical disease severity between viral co-infections and single respiratory infections were documented. The suggested increased risk of mortality observed amongst children with viral co-infections requires further investigation.",2014 Jun 16,"['Asner, Sandra A.', 'Science, Michelle E.', 'Tran, Dat', 'Smieja, Marek', 'Merglen, Arnaud', 'Mertz, Dominik']",PLoS One,,,True
181d47c4050ebc63d4831f8dd0df88b785bf4985,PMC,"Antimicrobial, Antiviral and Immunomodulatory Activity Studies of Pelargonium sidoides (EPs(®) 7630) in the Context of Health Promotion",http://dx.doi.org/10.3390/ph4101295,PMC4060126,27721327,CC BY,"Pelargonium species contribute significantly to the health care of a large population in the Southern African region, as part of a long-standing medical system intimately linked to traditional healing practices. Most notably, extracts of the roots of P. sidoides have commonly been applied for the treatment of dysentery and diarrhoea but only occasionally for respiratory complaints. Clinical trials have shown that a modern aqueous-ethanolic formulation of P. sidoides extracts (EPs(®) 7630) is an efficacious treatment for disorders of the respiratory tract, for example bronchitis and sinusitis. It should be noted that EPs(®) 7630 is the most widely investigated extract and therefore is the focus of this review. In order to provide a rationale for its therapeutic activity extracts have been evaluated for antibacterial activity and for their effects on non-specific immune functions. Only moderate direct antibacterial capabilities against a spectrum of bacteria, including Mycobacteria strains, have been noted. In contrast, a large body of in vitro studies has provided convincing evidence for an anti-infective principle associated with activation of the non-specific immune system. Interestingly, significant inhibition of interaction between bacteria and host cells, a key to the pathogenesis of respiratory tract infections, has emerged from recent studies. In addition, antiviral effects have been demonstrated, including inhibition of the replication of respiratory viruses and the enzymes haemagglutinin and neuraminidase. Besides, an increase of cilliary beat frequency of respiratory cells may contribute to the beneficial effects of P. sidoides extracts. This example provides a compelling argument for continuing the exploration of Nature and traditional medical systems as a source of therapeutically useful herbal medicines.",2011 Oct 10,"Kolodziej, Herbert",Pharmaceuticals (Basel),,,True
5c4e986c0995292d3e3839bb20c20b95039ae9d4,PMC,ELR(+) chemokine signaling in host defense and disease in a viral model of central nervous system disease,http://dx.doi.org/10.3389/fncel.2014.00165,PMC4060560,24987333,CC BY,"Intracranial infection of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of susceptible strains of mice results in an acute encephalomyelitis, accompanied by viral replication in glial cells and robust infiltration of virus-specific T cells that contribute to host defense through cytokine secretion and cytolytic activity. Mice surviving the acute stage of disease develop an immune-mediated demyelinating disease, characterized by viral persistence in white matter tracts and a chronic neuroinflammatory response dominated by T cells and macrophages. Chemokines and their corresponding chemokine receptors are dynamically expressed throughout viral infection of the CNS, influencing neuroinflammation by regulating immune cell infltration and glial biology. This review is focused upon the pleiotropic chemokine receptor CXCR2 and its effects upon neutrophils and oligodendrocytes during JHMV infection and a number of other models of CNS inflammation.",2014 Jun 17,"['Hosking, Martin P.', 'Lane, Thomas E.']",Front Cell Neurosci,,,True
9761b5e2c50841879b9ec0fff753ec88ece36744,PMC,"Coronavirus infection, ER stress, apoptosis and innate immunity",http://dx.doi.org/10.3389/fmicb.2014.00296,PMC4060729,24987391,CC BY,"The replication of coronavirus, a family of important animal and human pathogens, is closely associated with the cellular membrane compartments, especially the endoplasmic reticulum (ER). Coronavirus infection of cultured cells was previously shown to cause ER stress and induce the unfolded protein response (UPR), a process that aims to restore the ER homeostasis by global translation shutdown and increasing the ER folding capacity. However, under prolonged ER stress, UPR can also induce apoptotic cell death. Accumulating evidence from recent studies has shown that induction of ER stress and UPR may constitute a major aspect of coronavirus–host interaction. Activation of the three branches of UPR modulates a wide variety of signaling pathways, such as mitogen-activated protein (MAP) kinase activation, autophagy, apoptosis, and innate immune response. ER stress and UPR activation may therefore contribute significantly to the viral replication and pathogenesis during coronavirus infection. In this review, we summarize the current knowledge on coronavirus-induced ER stress and UPR activation, with emphasis on their cross-talking to apoptotic signaling.",2014 Jun 17,"['Fung, To S.', 'Liu, Ding X.']",Front Microbiol,,,True
ba2009991ed471ace18c92633780cd180404c4a9,PMC,Package of NDV-Pseudotyped HIV-Luc Virus and Its Application in the Neutralization Assay for NDV Infection,http://dx.doi.org/10.1371/journal.pone.0099905,PMC4061091,24937158,CC BY,"Newcastle disease virus (NDV) is a member of the Paramyxovirinae subfamily and can infect most species of birds. It has been a great threat for the poultry industry all around the world. In this report, we successfully produced infectious pseudotyped pNL4-3-Luc-R(−)E(−) (HIV-Luc) viruses with the HN and F envelope proteins of NDV. Further investigation revealed the cytoplasmic domains of HN and F, especially HN, plays a significant role in the infection efficiency of these pseudotyped HIV-Luc viruses. Replacement of, or direct fusion to the cytoplasmic domain of the HN protein by that of vesicular stomatitis virus G (VSV-G) could greatly enhance or destroy the infective potential of HN and F-pseudotyped (NDV-pseudotyped) HIV-Luc virus. We further established a novel neutralization assay to evaluate neutralizing antibodies against NDV with the NDV-pseudotyped HIV-Luc viruses. Comparative neutralization data indicate that the results determined by using the NDV-pseudotyped HIV-Luc viruses are as reliable as those by the conventional virus-neutralization assay (VN test) with native NDV. Moreover, the results show that the novel neutralization assay is more sensitive than the VN test.",2014 Jun 17,"['Wang, Bin', 'Wang, Bin', 'Liu, Peixin', 'Li, Tao', 'Si, Wei', 'Xiu, Jinsheng', 'Liu, Henggui']",PLoS One,,,True
ef58c6e2790539f30df14acc260ae2af4b5f3d1f,PMC,Can’t RIDD off viruses,http://dx.doi.org/10.3389/fmicb.2014.00292,PMC4061530,24995003,CC BY,"The mammalian genome has evolved to encode a battery of mechanisms, to mitigate a progression in the life cycle of an invasive viral pathogen. Although apparently disadvantaged by their dependence on the host biosynthetic processes, an immensely faster rate of evolution provides viruses with an edge in this conflict. In this review, I have discussed the potential anti-virus activity of inositol-requiring enzyme 1 (IRE1), a well characterized effector of the cellular homeostatic response to an overloading of the endoplasmic reticulum (ER) protein-folding capacity. IRE1, an ER-membrane-resident ribonuclease (RNase), upon activation catalyses regulated cleavage of select protein-coding and non-coding host RNAs, using an RNase domain which is homologous to that of the known anti-viral effector RNaseL. The latter operates as part of the Oligoadenylate synthetase OAS/RNaseL system of anti-viral defense mechanism. Protein-coding RNA substrates are differentially treated by the IRE1 RNase to either augment, through cytoplasmic splicing of an intron in the Xbp1 transcript, or suppress gene expression. This referred suppression of gene expression is mediated through degradative cleavage of a select cohort of cellular RNA transcripts, initiating the regulated IRE1-dependent decay (RIDD) pathway. The review first discusses the anti-viral mechanism of the OAS/RNaseL system and evasion tactics employed by different viruses. This is followed by a review of the RIDD pathway and its potential effect on the stability of viral RNAs. I conclude with a comparison of the enzymatic activity of the two RNases followed by deliberations on the physiological consequences of their activation.",2014 Jun 18,"Bhattacharyya, Sankar",Front Microbiol,,,True
4055104522be7b53cb86035004c9406b118199f7,PMC,A Compact Immunoassay Platform Based on a Multicapillary Glass Plate,http://dx.doi.org/10.3390/s140509132,PMC4063063,24859022,CC BY,"A highly sensitive, rapid immunoassay performed in the multi-channels of a micro-well array consisting of a multicapillary glass plate (MCP) and a polydimethylsiloxane (PDMS) slide is described. The micro-dimensions and large surface area of the MCP permitted the diffusion distance to be decreased and the reaction efficiency to be increased. To confirm the concept of the method, human immunoglobulin A (h-IgA) was measured using both the proposed immunoassay system and the traditional 96-well plate method. The proposed method resulted in a 1/5-fold decrease of immunoassay time, and a 1/56-fold cut in reagent consumption with a 0.05 ng/mL of limit of detection (LOD) for IgA. The method was also applied to saliva samples obtained from healthy volunteers. The results correlated well to those obtained by the 96-well plate method. The method has the potential for use in disease diagnostic or on-site immunoassays.",2014 May 23,"['Xue, Shuhua', 'Zeng, Hulie', 'Yang, Jianmin', 'Nakajima, Hizuru', 'Uchiyama, Katsumi']",Sensors (Basel),,,True
d8a900446a0ac1e4d0096ab06f805c253a75523c,PMC,"Viral Etiologies of Hospitalized Acute Lower Respiratory Infection Patients in China, 2009-2013",http://dx.doi.org/10.1371/journal.pone.0099419,PMC4063718,24945280,CC BY,"BACKGROUND: Acute lower respiratory infections (ALRIs) are an important cause of acute illnesses and mortality worldwide and in China. However, a large-scale study on the prevalence of viral infections across multiple provinces and seasons has not been previously reported from China. Here, we aimed to identify the viral etiologies associated with ALRIs from 22 Chinese provinces. METHODS AND FINDINGS: Active surveillance for hospitalized ALRI patients in 108 sentinel hospitals in 24 provinces of China was conducted from January 2009-September 2013. We enrolled hospitalized all-age patients with ALRI, and collected respiratory specimens, blood or serum collected for diagnostic testing for respiratory syncytial virus (RSV), human influenza virus, adenoviruses (ADV), human parainfluenza virus (PIV), human metapneumovirus (hMPV), human coronavirus (hCoV) and human bocavirus (hBoV). We included 28,369 ALRI patients from 81 (of the 108) sentinel hospitals in 22 (of the 24) provinces, and 10,387 (36.6%) were positive for at least one etiology. The most frequently detected virus was RSV (9.9%), followed by influenza (6.6%), PIV (4.8%), ADV (3.4%), hBoV (1.9), hMPV (1.5%) and hCoV (1.4%). Co-detections were found in 7.2% of patients. RSV was the most common etiology (17.0%) in young children aged <2 years. Influenza viruses were the main cause of the ALRIs in adults and elderly. PIV, hBoV, hMPV and ADV infections were more frequent in children, while hCoV infection was distributed evenly in all-age. There were clear seasonal peaks for RSV, influenza, PIV, hBoV and hMPV infections. CONCLUSIONS: Our findings could serve as robust evidence for public health authorities in drawing up further plans to prevent and control ALRIs associated with viral pathogens. RSV is common in young children and prevention measures could have large public health impact. Influenza was most common in adults and influenza vaccination should be implemented on a wider scale in China.",2014 Jun 19,"['Feng, Luzhao', 'Li, Zhongjie', 'Zhao, Shiwen', 'Nair, Harish', 'Lai, Shengjie', 'Xu, Wenbo', 'Li, Mengfeng', 'Wu, Jianguo', 'Ren, Lili', 'Liu, Wei', 'Yuan, Zhenghong', 'Chen, Yu', 'Wang, Xinhua', 'Zhao, Zhuo', 'Zhang, Honglong', 'Li, Fu', 'Ye, Xianfei', 'Li, Sa', 'Feikin, Daniel', 'Yu, Hongjie', 'Yang, Weizhong']",PLoS One,,,True
359aef6ff466266be0ea21eb665fb887cec16713,PMC,Associations between Single Nucleotide Polymorphisms in Cellular Viral Receptors and Attachment Factor-Related Genes and Humoral Immunity to Rubella Vaccination,http://dx.doi.org/10.1371/journal.pone.0099997,PMC4063777,24945853,CC BY,"BACKGROUND: Viral attachment and cell entry host factors are important for viral replication, pathogenesis, and the generation and sustenance of immune responses after infection and/or vaccination, and are plausible genetic regulators of vaccine-induced immunity. METHODS: Using a tag-SNP approach in candidate gene study, we assessed the role of selected cell surface receptor genes, attachment factor-related genes, along with other immune genes in the genetic control of immune response variations after live rubella vaccination in two independent study cohorts. RESULTS: Our analysis revealed evidence for multiple associations between genetic variants in the PVR, PVRL2, CD209/DC-SIGN, RARB, MOG, IL6 and other immune function-related genes and rubella-specific neutralizing antibodies after vaccination (meta p-value <0.05). CONCLUSION: Our results indicate that multiple SNPs from genes involved in cell adhesion, viral attachment, and viral entry, as well as others in genes involved in signaling and/or immune response regulation, play a role in modulating humoral immune responses following live rubella vaccination.",2014 Jun 19,"['Haralambieva, Iana H.', 'Lambert, Nathaniel D.', 'Ovsyannikova, Inna G.', 'Kennedy, Richard B.', 'Larrabee, Beth R.', 'Pankratz, V. Shane', 'Poland, Gregory A.']",PLoS One,,,True
d647c6b65ee08b38ecbd2bb85de064df41f7cf0f,PMC,Public perceptions of non-pharmaceutical interventions for reducing transmission of respiratory infection: systematic review and synthesis of qualitative studies,http://dx.doi.org/10.1186/1471-2458-14-589,PMC4063987,24920395,CC BY,"BACKGROUND: Non-pharmaceutical public health interventions may provide simple, low-cost, effective ways of minimising the transmission and impact of acute respiratory infections in pandemic and non-pandemic contexts. Understanding what influences the uptake of non-pharmaceutical interventions such as hand and respiratory hygiene, mask wearing and social distancing could help to inform the development of effective public health advice messages. The aim of this synthesis was to explore public perceptions of non-pharmaceutical interventions that aim to reduce the transmission of acute respiratory infections. METHODS: Five online databases (MEDLINE, PsycINFO, CINAHL, EMBASE and Web of Science) were systematically searched. Reference lists of articles were also examined. We selected papers that used a qualitative research design to explore perceptions and beliefs about non-pharmaceutical interventions to reduce transmission of acute respiratory infections. We excluded papers that only explored how health professionals or children viewed non-pharmaceutical respiratory infection control. Three authors performed data extraction and assessment of study quality. Thematic analysis and components of meta-ethnography were adopted to synthesise findings. RESULTS: Seventeen articles from 16 studies in 9 countries were identified and reviewed. Seven key themes were identified: perceived benefits of non-pharmaceutical interventions, perceived disadvantages of non-pharmaceutical interventions, personal and cultural beliefs about infection transmission, diagnostic uncertainty in emerging respiratory infections, perceived vulnerability to infection, anxiety about emerging respiratory infections and communications about emerging respiratory infections. The synthesis showed that some aspects of non-pharmaceutical respiratory infection control (particularly hand and respiratory hygiene) were viewed as familiar and socially responsible actions to take. There was ambivalence about adopting isolation and personal distancing behaviours in some contexts due to their perceived adverse impact and potential to attract social stigma. Common perceived barriers included beliefs about infection transmission, personal vulnerability to respiratory infection and concerns about self-diagnosis in emerging respiratory infections. CONCLUSIONS: People actively evaluate non-pharmaceutical interventions in terms of their perceived necessity, efficacy, acceptability, and feasibility. To enhance uptake, it will be necessary to address key barriers, such as beliefs about infection transmission, rejection of personal risk of infection and concern about the potential costs and stigma associated with some interventions.",2014 Jun 11,"['Teasdale, Emma', 'Santer, Miriam', 'Geraghty, Adam W A', 'Little, Paul', 'Yardley, Lucy']",BMC Public Health,,,True
c6024a8ca787b4af96d36292b86479031416a0b6,PMC,A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures,http://dx.doi.org/10.1186/1471-2105-15-147,PMC4064103,24884954,CC BY,"BACKGROUND: Improving accuracy and efficiency of computational methods that predict pseudoknotted RNA secondary structures is an ongoing challenge. Existing methods based on free energy minimization tend to be very slow and are limited in the types of pseudoknots that they can predict. Incorporating known structural information can improve prediction accuracy; however, there are not many methods for prediction of pseudoknotted structures that can incorporate structural information as input. There is even less understanding of the relative robustness of these methods with respect to partial information. RESULTS: We present a new method, Iterative HFold, for pseudoknotted RNA secondary structure prediction. Iterative HFold takes as input a pseudoknot-free structure, and produces a possibly pseudoknotted structure whose energy is at least as low as that of any (density-2) pseudoknotted structure containing the input structure. Iterative HFold leverages strengths of earlier methods, namely the fast running time of HFold, a method that is based on the hierarchical folding hypothesis, and the energy parameters of HotKnots V2.0. Our experimental evaluation on a large data set shows that Iterative HFold is robust with respect to partial information, with average accuracy on pseudoknotted structures steadily increasing from roughly 54% to 79% as the user provides up to 40% of the input structure. Iterative HFold is much faster than HotKnots V2.0, while having comparable accuracy. Iterative HFold also has significantly better accuracy than IPknot on our HK-PK and IP-pk168 data sets. CONCLUSIONS: Iterative HFold is a robust method for prediction of pseudoknotted RNA secondary structures, whose accuracy with more than 5% information about true pseudoknot-free structures is better than that of IPknot, and with about 35% information about true pseudoknot-free structures compares well with that of HotKnots V2.0 while being significantly faster. Iterative HFold and all data used in this work are freely available at http://www.cs.ubc.ca/~hjabbari/software.php.",2014 May 18,"['Jabbari, Hosna', 'Condon, Anne']",BMC Bioinformatics,,,True
a04f2512a74dc49c895acb697ee84d9a22101dc1,PMC,A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures,http://dx.doi.org/10.1186/1471-2105-15-147,PMC4064103,24884954,CC BY,"BACKGROUND: Improving accuracy and efficiency of computational methods that predict pseudoknotted RNA secondary structures is an ongoing challenge. Existing methods based on free energy minimization tend to be very slow and are limited in the types of pseudoknots that they can predict. Incorporating known structural information can improve prediction accuracy; however, there are not many methods for prediction of pseudoknotted structures that can incorporate structural information as input. There is even less understanding of the relative robustness of these methods with respect to partial information. RESULTS: We present a new method, Iterative HFold, for pseudoknotted RNA secondary structure prediction. Iterative HFold takes as input a pseudoknot-free structure, and produces a possibly pseudoknotted structure whose energy is at least as low as that of any (density-2) pseudoknotted structure containing the input structure. Iterative HFold leverages strengths of earlier methods, namely the fast running time of HFold, a method that is based on the hierarchical folding hypothesis, and the energy parameters of HotKnots V2.0. Our experimental evaluation on a large data set shows that Iterative HFold is robust with respect to partial information, with average accuracy on pseudoknotted structures steadily increasing from roughly 54% to 79% as the user provides up to 40% of the input structure. Iterative HFold is much faster than HotKnots V2.0, while having comparable accuracy. Iterative HFold also has significantly better accuracy than IPknot on our HK-PK and IP-pk168 data sets. CONCLUSIONS: Iterative HFold is a robust method for prediction of pseudoknotted RNA secondary structures, whose accuracy with more than 5% information about true pseudoknot-free structures is better than that of IPknot, and with about 35% information about true pseudoknot-free structures compares well with that of HotKnots V2.0 while being significantly faster. Iterative HFold and all data used in this work are freely available at http://www.cs.ubc.ca/~hjabbari/software.php.",2014 May 18,"['Jabbari, Hosna', 'Condon, Anne']",BMC Bioinformatics,,,False
a686bbe47aebbb5fd7c29a4f3da4f83271ff9c3e,PMC,A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures,http://dx.doi.org/10.1186/1471-2105-15-147,PMC4064103,24884954,CC BY,"BACKGROUND: Improving accuracy and efficiency of computational methods that predict pseudoknotted RNA secondary structures is an ongoing challenge. Existing methods based on free energy minimization tend to be very slow and are limited in the types of pseudoknots that they can predict. Incorporating known structural information can improve prediction accuracy; however, there are not many methods for prediction of pseudoknotted structures that can incorporate structural information as input. There is even less understanding of the relative robustness of these methods with respect to partial information. RESULTS: We present a new method, Iterative HFold, for pseudoknotted RNA secondary structure prediction. Iterative HFold takes as input a pseudoknot-free structure, and produces a possibly pseudoknotted structure whose energy is at least as low as that of any (density-2) pseudoknotted structure containing the input structure. Iterative HFold leverages strengths of earlier methods, namely the fast running time of HFold, a method that is based on the hierarchical folding hypothesis, and the energy parameters of HotKnots V2.0. Our experimental evaluation on a large data set shows that Iterative HFold is robust with respect to partial information, with average accuracy on pseudoknotted structures steadily increasing from roughly 54% to 79% as the user provides up to 40% of the input structure. Iterative HFold is much faster than HotKnots V2.0, while having comparable accuracy. Iterative HFold also has significantly better accuracy than IPknot on our HK-PK and IP-pk168 data sets. CONCLUSIONS: Iterative HFold is a robust method for prediction of pseudoknotted RNA secondary structures, whose accuracy with more than 5% information about true pseudoknot-free structures is better than that of IPknot, and with about 35% information about true pseudoknot-free structures compares well with that of HotKnots V2.0 while being significantly faster. Iterative HFold and all data used in this work are freely available at http://www.cs.ubc.ca/~hjabbari/software.php.",2014 May 18,"['Jabbari, Hosna', 'Condon, Anne']",BMC Bioinformatics,,,False
88122d733a2f4dcfa0aed0803994aa7402c1c369,PMC,A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures,http://dx.doi.org/10.1186/1471-2105-15-147,PMC4064103,24884954,CC BY,"BACKGROUND: Improving accuracy and efficiency of computational methods that predict pseudoknotted RNA secondary structures is an ongoing challenge. Existing methods based on free energy minimization tend to be very slow and are limited in the types of pseudoknots that they can predict. Incorporating known structural information can improve prediction accuracy; however, there are not many methods for prediction of pseudoknotted structures that can incorporate structural information as input. There is even less understanding of the relative robustness of these methods with respect to partial information. RESULTS: We present a new method, Iterative HFold, for pseudoknotted RNA secondary structure prediction. Iterative HFold takes as input a pseudoknot-free structure, and produces a possibly pseudoknotted structure whose energy is at least as low as that of any (density-2) pseudoknotted structure containing the input structure. Iterative HFold leverages strengths of earlier methods, namely the fast running time of HFold, a method that is based on the hierarchical folding hypothesis, and the energy parameters of HotKnots V2.0. Our experimental evaluation on a large data set shows that Iterative HFold is robust with respect to partial information, with average accuracy on pseudoknotted structures steadily increasing from roughly 54% to 79% as the user provides up to 40% of the input structure. Iterative HFold is much faster than HotKnots V2.0, while having comparable accuracy. Iterative HFold also has significantly better accuracy than IPknot on our HK-PK and IP-pk168 data sets. CONCLUSIONS: Iterative HFold is a robust method for prediction of pseudoknotted RNA secondary structures, whose accuracy with more than 5% information about true pseudoknot-free structures is better than that of IPknot, and with about 35% information about true pseudoknot-free structures compares well with that of HotKnots V2.0 while being significantly faster. Iterative HFold and all data used in this work are freely available at http://www.cs.ubc.ca/~hjabbari/software.php.",2014 May 18,"['Jabbari, Hosna', 'Condon, Anne']",BMC Bioinformatics,,,False
68eb9f309e762e8265822b96e7a6c6fa5814e959,PMC,A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures,http://dx.doi.org/10.1186/1471-2105-15-147,PMC4064103,24884954,CC BY,"BACKGROUND: Improving accuracy and efficiency of computational methods that predict pseudoknotted RNA secondary structures is an ongoing challenge. Existing methods based on free energy minimization tend to be very slow and are limited in the types of pseudoknots that they can predict. Incorporating known structural information can improve prediction accuracy; however, there are not many methods for prediction of pseudoknotted structures that can incorporate structural information as input. There is even less understanding of the relative robustness of these methods with respect to partial information. RESULTS: We present a new method, Iterative HFold, for pseudoknotted RNA secondary structure prediction. Iterative HFold takes as input a pseudoknot-free structure, and produces a possibly pseudoknotted structure whose energy is at least as low as that of any (density-2) pseudoknotted structure containing the input structure. Iterative HFold leverages strengths of earlier methods, namely the fast running time of HFold, a method that is based on the hierarchical folding hypothesis, and the energy parameters of HotKnots V2.0. Our experimental evaluation on a large data set shows that Iterative HFold is robust with respect to partial information, with average accuracy on pseudoknotted structures steadily increasing from roughly 54% to 79% as the user provides up to 40% of the input structure. Iterative HFold is much faster than HotKnots V2.0, while having comparable accuracy. Iterative HFold also has significantly better accuracy than IPknot on our HK-PK and IP-pk168 data sets. CONCLUSIONS: Iterative HFold is a robust method for prediction of pseudoknotted RNA secondary structures, whose accuracy with more than 5% information about true pseudoknot-free structures is better than that of IPknot, and with about 35% information about true pseudoknot-free structures compares well with that of HotKnots V2.0 while being significantly faster. Iterative HFold and all data used in this work are freely available at http://www.cs.ubc.ca/~hjabbari/software.php.",2014 May 18,"['Jabbari, Hosna', 'Condon, Anne']",BMC Bioinformatics,,,False
9ca17c3afd9591b30a57bb00f6af2957f37c1b8a,PMC,"Molecular epidemiology of Porcine torovirus (PToV) in Sichuan Province, China: 2011–2013",http://dx.doi.org/10.1186/1743-422X-11-106,PMC4064267,24903213,CC BY,"BACKGROUND: Porcine torovirus (PToV) is a member of the genus Torovirus which is responsible for gastrointestinal disease in both human beings and animals with particular prevalence in youth. Torovirus infections are generally asymptomatic, however, their presence may worsen disease consequences in concurrent infections with other enteric pathogens. METHODS: A total of 872 diarrheic fecal samples from pigs of different ages were collected from 12 districts of Sichuan Province in the southwest of China. RT-PCR was done with PToV S gene specific primers to detect the presence of PToV positive samples. M gene specific primers were used with the PToV positive samples and the genes were sequenced. A phylogenetic tree was constructed based on the M gene nucleotide sequences from the 19 selected novel Sichuan strains and 21 PToV and BToV M gene sequences from GenBank. RESULTS: A total of 331 (37.96%, 331/872) samples were found to be positive for PToV and the highest prevalence was observed in piglets aged from 1 to 3 weeks old. Through phylogenetic inference the 40 PToV M gene containing sequences were placed into two genotypes (I & II). The 19 novel Sichuan strains of genotype I showed strong correlations to two Korean gene sequences (GU-07-56-11 and GU-07-56-22). Amino-acid sequence analysis of the 40 PToV M gene strains revealed that the M gene protein was highly conserved. CONCLUSIONS: This study uncovered the presence of PToV in Sichuan Province, and demonstrated the need for continuous surveillance PToV of epidemiology.",2014 Jun 5,"['Zhou, Lu', 'Wei, Haoche', 'Zhou, Yuancheng', 'Xu, Zhiwen', 'Zhu, Ling', 'Horne, Jim']",Virol J,,,True
e10af65e4c33f25a580260de1b277ca738dcc886,PMC,"Characterization of the Ectodomain of the Envelope Protein of Dengue Virus Type 4: Expression, Membrane Association, Secretion and Particle Formation in the Absence of Precursor Membrane Protein",http://dx.doi.org/10.1371/journal.pone.0100641,PMC4065094,24950216,CC BY,"BACKGROUND: The envelope (E) of dengue virus (DENV) is the major target of neutralizing antibodies and vaccine development. After biosynthesis E protein forms a heterodimer with precursor membrane (prM) protein. Recent reports of infection enhancement by anti-prM monoclonal antibodies (mAbs) suggest anti-prM responses could be potentially harmful. Previously, we studied a series of C-terminal truncation constructs expressing DENV type 4 prM/E or E proteins and found the ectodomain of E protein alone could be recognized by all 12 mAbs tested, suggesting E protein ectodomain as a potential subunit immunogen without inducing anti-prM response. The characteristics of DENV E protein ectodomain in the absence of prM protein remains largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the expression, membrane association, glycosylation pattern, secretion and particle formation of E protein ectodomain of DENV4 in the presence or absence of prM protein. E protein ectodomain associated with membrane in or beyond trans-Golgi and contained primarily complex glycans, whereas full-length E protein associated with ER membrane and contained high mannose glycans. In the absence of prM protein, E protein ectodomain can secrete as well as form particles of approximately 49 nm in diameter, as revealed by sucrose gradient ultracentrifugation with or without detergent and electron microscopy. Mutational analysis revealed that the secretion of E protein ectodomain was affected by N-linked glycosylation and could be restored by treatment with ammonia chloride. CONCLUSIONS/SIGNIFICANCE: Considering the enhancement of DENV infectivity by anti-prM antibodies, our findings provide new insights into the expression and secretion of E protein ectodomain in the absence of prM protein and contribute to future subunit vaccine design.",2014 Jun 20,"['Hsieh, Szu-Chia', 'Tsai, Wen-Yang', 'Nerurkar, Vivek R.', 'Wang, Wei-Kung']",PLoS One,,,True
2738ed5788b2eb1a42164c7ddff227105d5ae617,PMC,Maternal immunity enhances Mycoplasma hyopneumoniae vaccination induced cell-mediated immune responses in piglets,http://dx.doi.org/10.1186/1746-6148-10-124,PMC4065585,24903770,CC BY,"BACKGROUND: Passively acquired maternal derived immunity (MDI) is a double-edged sword. Maternal derived antibody-mediated immunity (AMI) and cell-mediated immunity (CMI) are critical immediate defenses for the neonate; however, MDI may interfere with the induction of active immunity in the neonate, i.e. passive interference. The effect of antigen-specific MDI on vaccine-induced AMI and CMI responses to Mycoplasma hyopneumoniae (M. hyopneumoniae) was assessed in neonatal piglets. To determine whether CMI and AMI responses could be induced in piglets with MDI, piglets with high and low levels of maternal M. hyopneumoniae-specific immunity were vaccinated against M. hyopneumoniae at 7 d of age. Piglet M. hyopneumoniae-specific antibody, lymphoproliferation, and delayed type hypersensitivity (DTH) responses were measured 7 d and 14 d post vaccination. RESULTS: Piglets with M. hyopneumoniae-specific MDI failed to show vaccine-induced AMI responses; there was no rise in M. hyopneumoniae antibody levels following vaccination of piglets in the presence of M. hyopneumoniae-specific MDI. However, piglets with M. hyopneumoniae-specific MDI had primary (antigen-specific lymphoproliferation) and secondary (DTH) M. hyopneumoniae-specific CMI responses following vaccination. CONCLUSIONS: In this study neonatal M. hyopneumoniae-specific CMI was not subject to passive interference by MDI. Further, it appears that both maternal derived and endogenous CMI contribute to M. hyopneumoniae-specific CMI responses in piglets vaccinated in the face of MDI.",2014 Jun 5,"['Bandrick, Meggan', 'Theis, Kara', 'Molitor, Thomas W']",BMC Vet Res,,,True
9adb161f0e769ea8de09f4138cc40f206d586003,PMC,Analysis of tetra- and hepta-nucleotides motifs promoting -1 ribosomal frameshifting in Escherichia coli,http://dx.doi.org/10.1093/nar/gku386,PMC4066793,24875478,CC BY,"Programmed ribosomal -1 frameshifting is a non-standard decoding process occurring when ribosomes encounter a signal embedded in the mRNA of certain eukaryotic and prokaryotic genes. This signal has a mandatory component, the frameshift motif: it is either a Z_ZZN tetramer or a X_XXZ_ZZN heptamer (where ZZZ and XXX are three identical nucleotides) allowing cognate or near-cognate repairing to the -1 frame of the A site or A and P sites tRNAs. Depending on the signal, the frameshifting frequency can vary over a wide range, from less than 1% to more than 50%. The present study combines experimental and bioinformatics approaches to carry out (i) a systematic analysis of the frameshift propensity of all possible motifs (16 Z_ZZN tetramers and 64 X_XXZ_ZZN heptamers) in Escherichia coli and (ii) the identification of genes potentially using this mode of expression amongst 36 Enterobacteriaceae genomes. While motif efficiency varies widely, a major distinctive rule of bacterial -1 frameshifting is that the most efficient motifs are those allowing cognate re-pairing of the A site tRNA from ZZN to ZZZ. The outcome of the genomic search is a set of 69 gene clusters, 59 of which constitute new candidates for functional utilization of -1 frameshifting.",2014 Jul 1,"['Sharma, Virag', 'Prère, Marie-Françoise', 'Canal, Isabelle', 'Firth, Andrew E.', 'Atkins, John F.', 'Baranov, Pavel V.', 'Fayet, Olivier']",Nucleic Acids Res,,,True
0369a40d60dd1a4366529493f90c3e5bcea8a0f4,PMC,Analysis of tetra- and hepta-nucleotides motifs promoting -1 ribosomal frameshifting in Escherichia coli,http://dx.doi.org/10.1093/nar/gku386,PMC4066793,24875478,CC BY,"Programmed ribosomal -1 frameshifting is a non-standard decoding process occurring when ribosomes encounter a signal embedded in the mRNA of certain eukaryotic and prokaryotic genes. This signal has a mandatory component, the frameshift motif: it is either a Z_ZZN tetramer or a X_XXZ_ZZN heptamer (where ZZZ and XXX are three identical nucleotides) allowing cognate or near-cognate repairing to the -1 frame of the A site or A and P sites tRNAs. Depending on the signal, the frameshifting frequency can vary over a wide range, from less than 1% to more than 50%. The present study combines experimental and bioinformatics approaches to carry out (i) a systematic analysis of the frameshift propensity of all possible motifs (16 Z_ZZN tetramers and 64 X_XXZ_ZZN heptamers) in Escherichia coli and (ii) the identification of genes potentially using this mode of expression amongst 36 Enterobacteriaceae genomes. While motif efficiency varies widely, a major distinctive rule of bacterial -1 frameshifting is that the most efficient motifs are those allowing cognate re-pairing of the A site tRNA from ZZN to ZZZ. The outcome of the genomic search is a set of 69 gene clusters, 59 of which constitute new candidates for functional utilization of -1 frameshifting.",2014 Jul 1,"['Sharma, Virag', 'Prère, Marie-Françoise', 'Canal, Isabelle', 'Firth, Andrew E.', 'Atkins, John F.', 'Baranov, Pavel V.', 'Fayet, Olivier']",Nucleic Acids Res,,,False
ea3edffefb5fa20412b31e223330af336503afaf,PMC,Accuracy of epidemiological inferences based on publicly available information: retrospective comparative analysis of line lists of human cases infected with influenza A(H7N9) in China,http://dx.doi.org/10.1186/1741-7015-12-88,PMC4066833,24885692,CC BY,"BACKGROUND: Appropriate public health responses to infectious disease threats should be based on best-available evidence, which requires timely reliable data for appropriate analysis. During the early stages of epidemics, analysis of ‘line lists’ with detailed information on laboratory-confirmed cases can provide important insights into the epidemiology of a specific disease. The objective of the present study was to investigate the extent to which reliable epidemiologic inferences could be made from publicly-available epidemiologic data of human infection with influenza A(H7N9) virus. METHODS: We collated and compared six different line lists of laboratory-confirmed human cases of influenza A(H7N9) virus infection in the 2013 outbreak in China, including the official line list constructed by the Chinese Center for Disease Control and Prevention plus five other line lists by HealthMap, Virginia Tech, Bloomberg News, the University of Hong Kong and FluTrackers, based on publicly-available information. We characterized clinical severity and transmissibility of the outbreak, using line lists available at specific dates to estimate epidemiologic parameters, to replicate real-time inferences on the hospitalization fatality risk, and the impact of live poultry market closure. RESULTS: Demographic information was mostly complete (less than 10% missing for all variables) in different line lists, but there were more missing data on dates of hospitalization, discharge and health status (more than 10% missing for each variable). The estimated onset to hospitalization distributions were similar (median ranged from 4.6 to 5.6 days) for all line lists. Hospital fatality risk was consistently around 20% in the early phase of the epidemic for all line lists and approached the final estimate of 35% afterwards for the official line list only. Most of the line lists estimated >90% reduction in incidence rates after live poultry market closures in Shanghai, Nanjing and Hangzhou. CONCLUSIONS: We demonstrated that analysis of publicly-available data on H7N9 permitted reliable assessment of transmissibility and geographical dispersion, while assessment of clinical severity was less straightforward. Our results highlight the potential value in constructing a minimum dataset with standardized format and definition, and regular updates of patient status. Such an approach could be particularly useful for diseases that spread across multiple countries.",2014 May 28,"['Lau, Eric HY', 'Zheng, Jiandong', 'Tsang, Tim K', 'Liao, Qiaohong', 'Lewis, Bryan', 'Brownstein, John S', 'Sanders, Sharon', 'Wong, Jessica Y', 'Mekaru, Sumiko R', 'Rivers, Caitlin', 'Wu, Peng', 'Jiang, Hui', 'Li, Yu', 'Yu, Jianxing', 'Zhang, Qian', 'Chang, Zhaorui', 'Liu, Fengfeng', 'Peng, Zhibin', 'Leung, Gabriel M', 'Feng, Luzhao', 'Cowling, Benjamin J', 'Yu, Hongjie']",BMC Med,,,True
af8d060acff4a631e09af5425cdab023103e9d8a,PMC,Accuracy of epidemiological inferences based on publicly available information: retrospective comparative analysis of line lists of human cases infected with influenza A(H7N9) in China,http://dx.doi.org/10.1186/1741-7015-12-88,PMC4066833,24885692,CC BY,"BACKGROUND: Appropriate public health responses to infectious disease threats should be based on best-available evidence, which requires timely reliable data for appropriate analysis. During the early stages of epidemics, analysis of ‘line lists’ with detailed information on laboratory-confirmed cases can provide important insights into the epidemiology of a specific disease. The objective of the present study was to investigate the extent to which reliable epidemiologic inferences could be made from publicly-available epidemiologic data of human infection with influenza A(H7N9) virus. METHODS: We collated and compared six different line lists of laboratory-confirmed human cases of influenza A(H7N9) virus infection in the 2013 outbreak in China, including the official line list constructed by the Chinese Center for Disease Control and Prevention plus five other line lists by HealthMap, Virginia Tech, Bloomberg News, the University of Hong Kong and FluTrackers, based on publicly-available information. We characterized clinical severity and transmissibility of the outbreak, using line lists available at specific dates to estimate epidemiologic parameters, to replicate real-time inferences on the hospitalization fatality risk, and the impact of live poultry market closure. RESULTS: Demographic information was mostly complete (less than 10% missing for all variables) in different line lists, but there were more missing data on dates of hospitalization, discharge and health status (more than 10% missing for each variable). The estimated onset to hospitalization distributions were similar (median ranged from 4.6 to 5.6 days) for all line lists. Hospital fatality risk was consistently around 20% in the early phase of the epidemic for all line lists and approached the final estimate of 35% afterwards for the official line list only. Most of the line lists estimated >90% reduction in incidence rates after live poultry market closures in Shanghai, Nanjing and Hangzhou. CONCLUSIONS: We demonstrated that analysis of publicly-available data on H7N9 permitted reliable assessment of transmissibility and geographical dispersion, while assessment of clinical severity was less straightforward. Our results highlight the potential value in constructing a minimum dataset with standardized format and definition, and regular updates of patient status. Such an approach could be particularly useful for diseases that spread across multiple countries.",2014 May 28,"['Lau, Eric HY', 'Zheng, Jiandong', 'Tsang, Tim K', 'Liao, Qiaohong', 'Lewis, Bryan', 'Brownstein, John S', 'Sanders, Sharon', 'Wong, Jessica Y', 'Mekaru, Sumiko R', 'Rivers, Caitlin', 'Wu, Peng', 'Jiang, Hui', 'Li, Yu', 'Yu, Jianxing', 'Zhang, Qian', 'Chang, Zhaorui', 'Liu, Fengfeng', 'Peng, Zhibin', 'Leung, Gabriel M', 'Feng, Luzhao', 'Cowling, Benjamin J', 'Yu, Hongjie']",BMC Med,,,False
c12642f0762cb4888b417ce295044080ab9202a6,PMC,Macrophage activation state determines the response to rhinovirus infection in a mouse model of allergic asthma,http://dx.doi.org/10.1186/1465-9921-15-63,PMC4066837,24907978,CC BY,"BACKGROUND: The mechanisms by which viruses cause asthma exacerbations are not precisely known. Previously, we showed that, in ovalbumin (OVA)-sensitized and -challenged mice with allergic airway inflammation, rhinovirus (RV) infection increases type 2 cytokine production from alternatively-activated (M2) airway macrophages, enhancing eosinophilic inflammation and airways hyperresponsiveness. In this paper, we tested the hypothesis that IL-4 signaling determines the state of macrophage activation and pattern of RV-induced exacerbation in mice with allergic airways disease. METHODS: Eight week-old wild type or IL-4 receptor knockout (IL-4R KO) mice were sensitized and challenged with OVA and inoculated with RV1B or sham HeLa cell lysate. RESULTS: In contrast to OVA-treated wild-type mice with both neutrophilic and eosinophilic airway inflammation, OVA-treated IL-4R KO mice showed increased neutrophilic inflammation with few eosinophils in the airways. Like wild-type mice, IL-4R KO mice showed OVA-induced airway hyperreactivity which was further exacerbated by RV. There was a shift in lung cytokines from a type 2-predominant response to a type 1 response, including production of IL-12p40 and TNF-α. IL-17A was also increased. RV infection of OVA-treated IL-4R KO mice further increased neutrophilic inflammation. Bronchoalveolar macrophages showed an M1 polarization pattern and ex vivo RV infection increased macrophage production of TNF-α, IFN-γ and IL-12p40. Finally, lung cells from OVA-treated IL-4R KO mice showed reduced CD206+ CD301+ M2 macrophages, decreased IL-13 and increased TNF-α and IL-17A production by F4/80+, CD11b+ macrophages. CONCLUSIONS: OVA-treated IL-4R KO mice show neutrophilic airway inflammation constituting a model of allergic, type 1 cytokine-driven neutrophilic asthma. In the absence of IL-4/IL-13 signaling, RV infection of OVA-treated mice increased type 1 cytokine and IL-17A production from conventionally-activated macrophages, augmenting neutrophilic rather than eosinophilic inflammation. In mice with allergic airways inflammation, IL-4R signaling determines macrophage activation state and the response to subsequent RV infection.",2014 Jun 7,"['Hong, Jun Young', 'Chung, Yutein', 'Steenrod, Jessica', 'Chen, Qiang', 'Lei, Jing', 'Comstock, Adam T', 'Goldsmith, Adam M', 'Bentley, J Kelley', 'Sajjan, Uma S', 'Hershenson, Marc B']",Respir Res,,,True
9c437ea3972c987ed041833f65535b2d4300e095,PMC,Difference in immune response in vaccinated and unvaccinated Swedish individuals after the 2009 influenza pandemic,http://dx.doi.org/10.1186/1471-2334-14-319,PMC4067073,24916787,CC BY,"BACKGROUND: Previous exposures to flu and subsequent immune responses may impact on 2009/2010 pandemic flu vaccine responses and clinical symptoms upon infection with the 2009 pandemic H1N1 influenza strain. Qualitative and quantitative differences in humoral and cellular immune responses associated with the flu vaccination in 2009/2010 (pandemic H1N1 vaccine) and natural infection have not yet been described in detail. We designed a longitudinal study to examine influenza- (flu-) specific immune responses and the association between pre-existing flu responses, symptoms of influenza-like illness (ILI), impact of pandemic flu infection, and pandemic flu vaccination in a cohort of 2,040 individuals in Sweden in 2009–2010. METHODS: Cellular flu-specific immune responses were assessed by whole-blood antigen stimulation assay, and humoral responses by a single radial hemolysis test. RESULTS: Previous seasonal flu vaccination was associated with significantly lower flu-specific IFN-γ responses (using a whole-blood assay) at study entry. Pandemic flu vaccination induced long-lived T-cell responses (measured by IFN-γ production) to influenza A strains, influenza B strains, and the matrix (M1) antigen. In contrast, individuals with pandemic flu infection (PCR positive) exhibited increased flu-specific T-cell responses shortly after onset of ILI symptoms but the immune response decreased after the flu season (spring 2010). We identified non-pandemic-flu vaccinated participants without ILI symptoms who showed an IFN-γ production profile similar to pandemic-flu infected participants, suggesting exposure without experiencing clinical symptoms. CONCLUSIONS: Strong and long-lived flu-M1 specific immune responses, defined by IFN-γ production, in individuals after vaccination suggest that M1-responses may contribute to protective cellular immune responses. Silent flu infections appeared to be frequent in 2009/2010. The pandemic flu vaccine induced qualitatively and quantitatively different humoral and cellular immune responses as compared to infection with the 2009 H1N1 pandemic H1N1 influenza strain.",2014 Jun 11,"['Magalhaes, Isabelle', 'Eriksson, Mikael', 'Linde, Charlotte', 'Muhammad, Rashid', 'Rane, Lalit', 'Ambati, Aditya', 'Axelsson-Robertson, Rebecca', 'Khalaj, Bahareh', 'Alvarez-Corrales, Nancy', 'Lapini, Giulia', 'Montomoli, Emanuele', 'Linde, Annika', 'Pedersen, Nancy L', 'Maeurer, Markus']",BMC Infect Dis,,,True
1434efe4d841738948735807bd1d1f1e9a36225e,PMC,Difference in immune response in vaccinated and unvaccinated Swedish individuals after the 2009 influenza pandemic,http://dx.doi.org/10.1186/1471-2334-14-319,PMC4067073,24916787,CC BY,"BACKGROUND: Previous exposures to flu and subsequent immune responses may impact on 2009/2010 pandemic flu vaccine responses and clinical symptoms upon infection with the 2009 pandemic H1N1 influenza strain. Qualitative and quantitative differences in humoral and cellular immune responses associated with the flu vaccination in 2009/2010 (pandemic H1N1 vaccine) and natural infection have not yet been described in detail. We designed a longitudinal study to examine influenza- (flu-) specific immune responses and the association between pre-existing flu responses, symptoms of influenza-like illness (ILI), impact of pandemic flu infection, and pandemic flu vaccination in a cohort of 2,040 individuals in Sweden in 2009–2010. METHODS: Cellular flu-specific immune responses were assessed by whole-blood antigen stimulation assay, and humoral responses by a single radial hemolysis test. RESULTS: Previous seasonal flu vaccination was associated with significantly lower flu-specific IFN-γ responses (using a whole-blood assay) at study entry. Pandemic flu vaccination induced long-lived T-cell responses (measured by IFN-γ production) to influenza A strains, influenza B strains, and the matrix (M1) antigen. In contrast, individuals with pandemic flu infection (PCR positive) exhibited increased flu-specific T-cell responses shortly after onset of ILI symptoms but the immune response decreased after the flu season (spring 2010). We identified non-pandemic-flu vaccinated participants without ILI symptoms who showed an IFN-γ production profile similar to pandemic-flu infected participants, suggesting exposure without experiencing clinical symptoms. CONCLUSIONS: Strong and long-lived flu-M1 specific immune responses, defined by IFN-γ production, in individuals after vaccination suggest that M1-responses may contribute to protective cellular immune responses. Silent flu infections appeared to be frequent in 2009/2010. The pandemic flu vaccine induced qualitatively and quantitatively different humoral and cellular immune responses as compared to infection with the 2009 H1N1 pandemic H1N1 influenza strain.",2014 Jun 11,"['Magalhaes, Isabelle', 'Eriksson, Mikael', 'Linde, Charlotte', 'Muhammad, Rashid', 'Rane, Lalit', 'Ambati, Aditya', 'Axelsson-Robertson, Rebecca', 'Khalaj, Bahareh', 'Alvarez-Corrales, Nancy', 'Lapini, Giulia', 'Montomoli, Emanuele', 'Linde, Annika', 'Pedersen, Nancy L', 'Maeurer, Markus']",BMC Infect Dis,,,True
8c2cfca9f2eee4a00231a2a3a2cfe1e60e798672,PMC,Inducing Dose Sparing with Inactivated Polio Virus Formulated in Adjuvant CAF01,http://dx.doi.org/10.1371/journal.pone.0100879,PMC4067388,24956110,CC BY,"The development of new low cost inactivated polio virus based vaccines (IPV) is a high priority, and will be required to eradicate polio. In addition, such a vaccine constitutes the only realistic polio vaccine in the post-eradication era. One way to reduce the cost of a vaccine is to increase immunogenicity by use of adjuvants. The CAF01 adjuvant has previously been shown to be a safe and potent adjuvant with several antigens, and here we show that in mice IPV formulated with CAF01 induced increased systemic protective immunity measured by binding and neutralization antibody titers in serum. CAF01 also influenced the kinetics of both the cellular and humoral response against IPV to produce a faster, as well as a stronger, response, dominated by IgG2a, IgG2b, and IgG2c isotypes as well as IPV specific T cells secreting IFN-γ/IL-2. Finally, as intestinal immunity is also a priority of polio vaccines, we present a vaccine strategy based on simultaneous priming at an intradermal and an intramuscular site that generate intestinal immune responses against polio virus. Taken together, the IPV-CAF01 formulation constitutes a new promising vaccine against polio with the ability to generate strong humoral and cellular immunity against the polio virus.",2014 Jun 23,"['Dietrich, Jes', 'Andreasen, Lars Vibe', 'Andersen, Peter', 'Agger, Else Marie']",PLoS One,,,True
458baa469db78afded4d1acdbc4b7d440a5f0a74,PMC,"Results From the First Six Years of National Sentinel Surveillance for Influenza in Kenya, July 2007–June 2013",http://dx.doi.org/10.1371/journal.pone.0098615,PMC4067481,24955962,CC0,"BACKGROUND: Recent studies have shown that influenza is associated with significant disease burden in many countries in the tropics, but until recently national surveillance for influenza was not conducted in most countries in Africa. METHODS: In 2007, the Kenyan Ministry of Health with technical support from the CDC-Kenya established a national sentinel surveillance system for influenza. At 11 hospitals, for every hospitalized patient with severe acute respiratory illness (SARI), and for the first three outpatients with influenza-like illness (ILI) per day, we collected both nasopharyngeal and oropharyngeal swabs. Beginning in 2008, we conducted in-hospital follow-up for SARI patients to determine outcome. Specimens were tested by real time RT-PCR for influenza A and B. Influenza A-positive specimens were subtyped for H1, H3, H5, and (beginning in May 2009) A(H1N1)pdm09. RESULTS: From July 1, 2007 through June 30, 2013, we collected specimens from 24,762 SARI and 14,013 ILI patients. For SARI and ILI case-patients, the median ages were 12 months and 16 months, respectively, and 44% and 47% were female. In all, 2,378 (9.6%) SARI cases and 2,041 (14.6%) ILI cases were positive for influenza viruses. Most influenza-associated SARI cases (58.6%) were in children <2 years old. Of all influenza-positive specimens, 78% were influenza A, 21% were influenza B, and 1% were influenza A/B coinfections. Influenza circulated in every month. In four of the six years influenza activity peaked during July–November. Of 9,419 SARI patients, 2.7% died; the median length of hospitalization was 4 days. CONCLUSIONS: During six years of surveillance in Kenya, influenza was associated with nearly 10 percent of hospitalized SARI cases and one-sixth of outpatient ILI cases. Most influenza-associated SARI and ILI cases were in children <2 years old; interventions to reduce the burden of influenza, such as vaccine, could consider young children as a priority group.",2014 Jun 23,"['Katz, Mark A.', 'Muthoka, Philip', 'Emukule, Gideon O.', 'Kalani, Rosalia', 'Njuguna, Henry', 'Waiboci, Lilian W.', 'Ahmed, Jamal A.', 'Bigogo, Godfrey', 'Feikin, Daniel R.', 'Njenga, Moses K.', 'Breiman, Robert F.', 'Mott, Joshua A.']",PLoS One,,,True
b7f529b58714037f09a19f78d9a06d68f1f15dd9,PMC,From gene to protein—experimental and clinical studies of ACE2 in blood pressure control and arterial hypertension,http://dx.doi.org/10.3389/fphys.2014.00227,PMC4067757,25009501,CC BY,"Hypertension is a major risk factor for stroke, coronary events, heart and renal failure, and the renin-angiotensin system (RAS) plays a major role in its pathogenesis. Within the RAS, angiotensin converting enzyme (ACE) converts angiotensin (Ang) I into the vasoconstrictor Ang II. An “alternate” arm of the RAS now exists in which ACE2 counterbalances the effects of the classic RAS through degradation of Ang II, and generation of the vasodilator Ang 1-7. ACE2 is highly expressed in the heart, blood vessels, and kidney. The catalytically active ectodomain of ACE2 undergoes shedding, resulting in ACE2 in the circulation. The ACE2 gene maps to a quantitative trait locus on the X chromosome in three strains of genetically hypertensive rats, suggesting that ACE2 may be a candidate gene for hypertension. It is hypothesized that disruption of tissue ACE/ACE2 balance results in changes in blood pressure, with increased ACE2 expression protecting against increased blood pressure, and ACE2 deficiency contributing to hypertension. Experimental hypertension studies have measured ACE2 in either the heart or kidney and/or plasma, and have reported that deletion or inhibition of ACE2 leads to hypertension, whilst enhancing ACE2 protects against the development of hypertension, hence increasing ACE2 may be a therapeutic option for the management of high blood pressure in man. There have been relatively few studies of ACE2, either at the gene or the circulating level in patients with hypertension. Plasma ACE2 activity is low in healthy subjects, but elevated in patients with cardiovascular risk factors or cardiovascular disease. Genetic studies have investigated ACE2 gene polymorphisms with either hypertension or blood pressure, and have produced largely inconsistent findings. This review discusses the evidence regarding ACE2 in experimental hypertension models and the association between circulating ACE2 activity and ACE2 polymorphisms with blood pressure and arterial hypertension in man.",2014 Jun 24,"['Patel, Sheila K.', 'Velkoska, Elena', 'Freeman, Melanie', 'Wai, Bryan', 'Lancefield, Terase F.', 'Burrell, Louise M.']",Front Physiol,,,True
df5401bebedec1ea63a7afebb3b4166f775fbd82,PMC,No Evidence of Viral Transmission following Long-Term Implantation of Agarose Encapsulated Porcine Islets in Diabetic Dogs,http://dx.doi.org/10.1155/2014/727483,PMC4068064,24995342,CC BY,"We have previously described the use of a double coated agarose-agarose porcine islet macrobead for the treatment of type I diabetes mellitus. In the current study, the long-term viral safety of macrobead implantation into pancreatectomized diabetic dogs treated with pravastatin (n = 3) was assessed while 2 dogs served as nonimplanted controls. A more gradual return to preimplant insulin requirements occurred after a 2nd implant procedure (days 148, 189, and >652) when compared to a first macrobead implantation (days 9, 21, and 21) in all macrobead implanted animals. In all three implanted dogs, porcine C-peptide was detected in the blood for at least 10 days following the first implant and for at least 26 days following the second implant. C-peptide was also present in the peritoneal fluid of all three implanted dogs at 6 months after 2nd implant and in 2 of 3 dogs at necropsy. Prescreening results of islet macrobeads and culture media prior to transplantation were negative for 13 viruses. No evidence of PERV or other viral transmission was found throughout the study. This study demonstrates that the long-term (2.4 years) implantation of agarose-agarose encapsulated porcine islets is a safe procedure in a large animal model of type I diabetes mellitus.",2014 Jun 5,"['Gazda, Lawrence S.', 'Vinerean, Horatiu V.', 'Laramore, Melissa A.', 'Hall, Richard D.', 'Carraway, Joseph W.', 'Smith, Barry H.']",J Diabetes Res,,,True
153bc127b399f445ca2ec0e0709379efaada43bc,PMC,Unanswered questions about the Middle East respiratory syndrome coronavirus (MERS-CoV),http://dx.doi.org/10.1186/1756-0500-7-358,PMC4068970,24920393,CC BY,"BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) represents a current threat to the Arabian Peninsula, and potential pandemic disease. As of June 3, 2014, MERS CoV has reportedly infected 688 people and killed 282. We briefly summarize the state of the outbreak, and highlight unanswered questions and various explanations for the observed epidemiology. FINDINGS: The continuing but infrequent cases of MERS-CoV reported over the past two years have been puzzling and difficult to explain. The epidemiology of MERS-CoV, with many sporadic cases and a few hospital outbreaks, yet no sustained epidemic, suggests a low reproductive number. Furthermore, a clear source of infection to humans remains unknown. Also puzzling is the fact that MERS-CoV has been present in Saudi Arabia over several mass gatherings, including the 2012 and 2013 Hajj and Umrah pilgrimages, which predispose to epidemics, without an epidemic arising. CONCLUSIONS: The observed epidemiology of MERS-CoV is quite distinct and does not clearly fit either a sporadic or epidemic pattern. Possible explanations of the unusual features of the epidemiology of MERS-CoV include sporadic ongoing infections from a non-human source; human to human transmission with a large proportion of undetected cases; or a combination of both. The virus has been identified in camels; however the mode of transmission of the virus to humans remains unknown, and many cases have no history of animal contact. In order to gain a better understanding of the epidemiology of MERS CoV, further investigation is warranted.",2014 Jun 11,"['Gardner, Lauren M', 'MacIntyre, C Raina']",BMC Res Notes,,,True
8eefe017d2a4fedeac3243fb76f3b417b16023f2,PMC,Bat Distribution Size or Shape as Determinant of Viral Richness in African Bats,http://dx.doi.org/10.1371/journal.pone.0100172,PMC4069033,24959855,CC BY,"The rising incidence of emerging infectious diseases (EID) is mostly linked to biodiversity loss, changes in habitat use and increasing habitat fragmentation. Bats are linked to a growing number of EID but few studies have explored the factors of viral richness in bats. These may have implications for role of bats as potential reservoirs. We investigated the determinants of viral richness in 15 species of African bats (8 Pteropodidae and 7 microchiroptera) in Central and West Africa for which we provide new information on virus infection and bat phylogeny. We performed the first comparative analysis testing the correlation of the fragmented geographical distribution (defined as the perimeter to area ratio) with viral richness in bats. Because of their potential effect, sampling effort, host body weight, ecological and behavioural traits such as roosting behaviour, migration and geographical range, were included into the analysis as variables. The results showed that the geographical distribution size, shape and host body weight have significant effects on viral richness in bats. Viral richness was higher in large-bodied bats which had larger and more fragmented distribution areas. Accumulation of viruses may be related to the historical expansion and contraction of bat species distribution range, with potentially strong effects of distribution edges on virus transmission. Two potential explanations may explain these results. A positive distribution edge effect on the abundance or distribution of some bat species could have facilitated host switches. Alternatively, parasitism could play a direct role in shaping the distribution range of hosts through host local extinction by virulent parasites. This study highlights the importance of considering the fragmentation of bat species geographical distribution in order to understand their role in the circulation of viruses in Africa.",2014 Jun 24,"['Maganga, Gaël D.', 'Bourgarel, Mathieu', 'Vallo, Peter', 'Dallo, Thierno D.', 'Ngoagouni, Carine', 'Drexler, Jan Felix', 'Drosten, Christian', 'Nakouné, Emmanuel R.', 'Leroy, Eric M.', 'Morand, Serge']",PLoS One,,,True
04f4cff6c1a32e0edb50bdb8daf00f82708a5142,PMC,Plasmodium vivax Antigen Discovery Based on Alpha-Helical Coiled Coil Protein Motif,http://dx.doi.org/10.1371/journal.pone.0100440,PMC4069070,24959747,CC BY,"Protein α-helical coiled coil structures that elicit antibody responses, which block critical functions of medically important microorganisms, represent a means for vaccine development. By using bioinformatics algorithms, a total of 50 antigens with α-helical coiled coil motifs orthologous to Plasmodium falciparum were identified in the P. vivax genome. The peptides identified in silico were chemically synthesized; circular dichroism studies indicated partial or high α-helical content. Antigenicity was evaluated using human sera samples from malaria-endemic areas of Colombia and Papua New Guinea. Eight of these fragments were selected and used to assess immunogenicity in BALB/c mice. ELISA assays indicated strong reactivity of serum samples from individuals residing in malaria-endemic regions and sera of immunized mice, with the α-helical coiled coil structures. In addition, ex vivo production of IFN-γ by murine mononuclear cells confirmed the immunogenicity of these structures and the presence of T-cell epitopes in the peptide sequences. Moreover, sera of mice immunized with four of the eight antigens recognized native proteins on blood-stage P. vivax parasites, and antigenic cross-reactivity with three of the peptides was observed when reacted with both the P. falciparum orthologous fragments and whole parasites. Results here point to the α-helical coiled coil peptides as possible P. vivax malaria vaccine candidates as were observed for P. falciparum. Fragments selected here warrant further study in humans and non-human primate models to assess their protective efficacy as single components or assembled as hybrid linear epitopes.",2014 Jun 24,"['Céspedes, Nora', 'Habel, Catherine', 'Lopez-Perez, Mary', 'Castellanos, Angélica', 'Kajava, Andrey V.', 'Servis, Catherine', 'Felger, Ingrid', 'Moret, Remy', 'Arévalo-Herrera, Myriam', 'Corradin, Giampietro', 'Herrera, Sócrates']",PLoS One,,,True
20308c2a1349e993e82115a8dc869c011298dd06,PMC,Epidemiology and Viral Etiology of the Influenza-Like Illness in Corsica during the 2012–2013 Winter: An Analysis of Several Sentinel Surveillance Systems,http://dx.doi.org/10.1371/journal.pone.0100388,PMC4069071,24959929,CC BY,"Influenza-like illness (ILI) surveillance is important to identify circulating and emerging/reemerging strains and unusual epidemiological trends. The present study aimed to give an accurate picture of the 2012–2013 ILI outbreak in Corsica by combining data from several surveillance systems: general practice, emergency general practice, hospital emergency units, intensive care units, and nursing homes. Twenty-eight respiratory viruses were retrospectively investigated from patients in general practice with ILI. Sequence analysis of the genetic changes in the hemagglutinin gene of influenza viruses (A(H1N1)pdm2009, A(H3N2) and B) was performed. The trends in ILI/influenza consultation rates and the relative illness ratios (RIRs) of having an ILI consultation were estimated by age group for the different surveillance systems analyzed. Of the 182 ILI patients enrolled by general practitioners, 57.7% tested positive for influenza viruses. Phylogenetic analyses suggested a genetic drift for influenza B and A(H3N2) viruses. The ILI/influenza surveillance systems showed similar trends and were well correlated. In accordance with virological data, the RIRs of having an ILI consultation were highest among the young (<15 years old) and decreased with age. No clusters of acute respiratory illness were declared by the sentinel nursing homes. This study is noteworthy in that it is the first extensive description of the 2012–2013 ILI outbreak in Corsica as monitored through several surveillance systems. To improve ILI surveillance in Corsica, a consortium that links together the complementary regional surveillance ILI systems described here is being implemented.",2014 Jun 24,"['Minodier, Laëtitia', 'Arena, Christophe', 'Heuze, Guillaume', 'Ruello, Marc', 'Amoros, Jean Pierre', 'Souty, Cécile', 'Varesi, Laurent', 'Falchi, Alessandra']",PLoS One,,,True
fc5cc0fedf50af659b515f25de57a6c7d841d342,PMC,"Yu Ping Feng San, an Ancient Chinese Herbal Decoction, Regulates the Expression of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 and the Activity of Intestinal Alkaline Phosphatase in Cultures",http://dx.doi.org/10.1371/journal.pone.0100382,PMC4072625,24967898,CC BY,"Yu Ping Feng San (YPFS), a Chinese herbal decoction comprising Astragali Radix (AR; Huangqi), Atractylodis Macrocephalae Rhizoma (AMR; Baizhu), and Saposhnikoviae Radix (SR; Fangfeng), has been used clinically to treat inflammatory bowel diseases (IBD). Previously, we demonstrated a dual role of YPFS in regulating cytokine release in cultured macrophages. In this study, we elucidated the anti-inflammatory effect of YPFS that is mediated through modulating the expression of three key enzymes involved in IBD: inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and intestinal alkaline phosphatase (IALP). In a lipopolysaccharide (LPS)-induced chronic-inflammation model of cultured murine macrophages, YPFS treatment suppressed the activation of iNOS and COX-2 expression in a dose-dependent manner. Conversely, application of YPFS in cultured small intestinal enterocytes markedly induced the expression of IALP in a time-dependent manner, which might strengthen the intestinal detoxification system. A duality of YPFS in modulating the expression of iNOS and COX-2 was determined here. The expression of iNOS and COX-2 in macrophages was induced by YPFS, and this activation was partially blocked by the NF-κB-specific inhibitor BAY 11-7082, indicating a role of NF-κB signaling. These YPFS-induced changes in gene regulation strongly suggest that the anti-inflammatory effects of YPFS are mediated through the regulation of inflammatory enzymes.",2014 Jun 26,"['Du, Crystal Y. Q.', 'Choi, Roy C. Y.', 'Dong, Tina T. X.', 'Lau, David T. W.', 'Tsim, Karl W. K.']",PLoS One,,,True
fa16032841f11e0924b539d21444915e3bcc9a0e,PMC,A Nucleic-Acid Hydrolyzing Single Chain Antibody Confers Resistance to DNA Virus Infection in HeLa Cells and C57BL/6 Mice,http://dx.doi.org/10.1371/journal.ppat.1004208,PMC4072776,24968358,CC BY,"Viral protein neutralizing antibodies have been developed but they are limited only to the targeted virus and are often susceptible to antigenic drift. Here, we present an alternative strategy for creating virus-resistant cells and animals by ectopic expression of a nucleic acid hydrolyzing catalytic 3D8 single chain variable fragment (scFv), which has both DNase and RNase activities. HeLa cells (SCH7072) expressing 3D8 scFv acquired significant resistance to DNA viruses. Virus challenging with Herpes simplex virus (HSV) in 3D8 scFv transgenic cells and fluorescence resonance energy transfer (FRET) assay based on direct DNA cleavage analysis revealed that the induced resistance in HeLa cells was acquired by the nucleic acid hydrolyzing catalytic activity of 3D8 scFv. In addition, pseudorabies virus (PRV) infection in WT C57BL/6 mice was lethal, whereas transgenic mice (STG90) that expressed high levels of 3D8 scFv mRNA in liver, muscle, and brain showed a 56% survival rate 5 days after PRV intramuscular infection. The antiviral effects against DNA viruses conferred by 3D8 scFv expression in HeLa cells as well as an in vivo mouse system can be attributed to the nuclease activity that inhibits viral genome DNA replication in the nucleus and/or viral mRNA translation in the cytoplasm. Our results demonstrate that the nucleic-acid hydrolyzing activity of 3D8 scFv confers viral resistance to DNA viruses in vitro in HeLa cells and in an in vivo mouse system.",2014 Jun 26,"['Lee, Gunsup', 'Yu, Jaelim', 'Cho, Seungchan', 'Byun, Sung-June', 'Kim, Dae Hyun', 'Lee, Taek-Kyun', 'Kwon, Myung-Hee', 'Lee, Sukchan']",PLoS Pathog,,,True
6a6327ac7ce00c6d5b2bffd0ff65c8476d94760b,PMC,Proof by synthesis of Tobacco mosaic virus,http://dx.doi.org/10.1186/gb-2014-15-5-r67,PMC4072989,24887356,CC BY,"BACKGROUND: Synthetic biology is a discipline that includes making life forms artificially from chemicals. Here, a DNA molecule was enzymatically synthesized in vitro from DNA templates made from oligonucleotides representing the text of the first Tobacco mosaic virus (TMV) sequence elucidated in 1982. No infectious DNA molecule of that seminal reference sequence exists, so the goal was to synthesize it and then build viral chimeras. RESULTS: RNA was transcribed from synthetic DNA and encapsidated with capsid protein in vitro to make synthetic virions. Plants inoculated with the virions did not develop symptoms. When two nucleotide mutations present in the original sequence, but not present in most other TMV sequences in GenBank, were altered to reflect the consensus, the derivative synthetic virions produced classic TMV symptoms. Chimeras were then made by exchanging TMV capsid protein DNA with Tomato mosaic virus (ToMV) and Barley stripe mosaic virus (BSMV) capsid protein DNA. Virus expressing ToMV capsid protein exhibited altered, ToMV-like symptoms in Nicotiana sylvestris. A hybrid ORF6 protein unknown to nature, created by substituting the capsid protein genes in the virus, was found to be a major symptom determinant in Nicotiana benthamiana. Virus expressing BSMV capsid protein did not have an extended host range to barley, but did produce novel symptoms in N. benthamiana. CONCLUSIONS: This first report of the chemical synthesis and artificial assembly of a plant virus corrects a long-standing error in the TMV reference genome sequence and reveals that unnatural hybrid virus proteins can alter symptoms unexpectedly.",2014 Apr 30,"Cooper, Bret",Genome Biol,,,True
7e216d0c059fbbc7cace4a9d12a48482ad781366,PMC,A Multi-Method Approach to Curriculum Development for In-Service Training in China’s Newly Established Health Emergency Response Offices,http://dx.doi.org/10.1371/journal.pone.0100892,PMC4074095,24971602,CC BY,"OBJECTIVE: To describe an innovative approach for developing and implementing an in-service curriculum in China for staff of the newly established health emergency response offices (HEROs), and that is generalisable to other settings. METHODS: The multi-method training needs assessment included reviews of the competency domains needed to implement the International Health Regulations (2005) as well as China’s policies and emergency regulations. The review, iterative interviews and workshops with experts in government, academia, the military, and with HERO staff were reviewed critically by an expert technical advisory panel. FINDINGS: Over 1600 participants contributed to curriculum development. Of the 18 competency domains identified as essential for HERO staff, nine were developed into priority in-service training modules to be conducted over 2.5 weeks. Experts from academia and experienced practitioners prepared and delivered each module through lectures followed by interactive problem-solving exercises and desktop simulations to help trainees apply, experiment with, and consolidate newly acquired knowledge and skills. CONCLUSION: This study adds to the emerging literature on China’s enduring efforts to strengthen its emergency response capabilities since the outbreak of SARS in 2003. The multi-method approach to curriculum development in partnership with senior policy-makers, researchers, and experienced practitioners can be applied in other settings to ensure training is responsive and customized to local needs, resources and priorities. Ongoing curriculum development should reflect international standards and be coupled with the development of appropriate performance support systems at the workplace for motivating staff to apply their newly acquired knowledge and skills effectively and creatively.",2014 Jun 27,"['Wang, Yadong', 'Li, Xiangrui', 'Yuan, Yiwen', 'Patel, Mahomed S.']",PLoS One,,,True
53c2f84a60048a66e83bd25c1521e7bc87efd5f4,PMC,Discovery of Novel GPVI Receptor Antagonists by Structure-Based Repurposing,http://dx.doi.org/10.1371/journal.pone.0101209,PMC4074120,24971515,CC BY,"Inappropriate platelet aggregation creates a cardiovascular risk that is largely managed with thienopyridines and aspirin. Although effective, these drugs carry risks of increased bleeding and drug ‘resistance’, underpinning a drive for new antiplatelet agents. To discover such drugs, one strategy is to identify a suitable druggable target and then find small molecules that modulate it. A good and unexploited target is the platelet collagen receptor, GPVI, which promotes thrombus formation. To identify inhibitors of GPVI that are safe and bioavailable, we docked a FDA-approved drug library into the GPVI collagen-binding site in silico. We now report that losartan and cinanserin inhibit GPVI-mediated platelet activation in a selective, competitive and dose-dependent manner. This mechanism of action likely underpins the cardioprotective effects of losartan that could not be ascribed to its antihypertensive effects. We have, therefore, identified small molecule inhibitors of GPVI-mediated platelet activation, and also demonstrated the utility of structure-based repurposing.",2014 Jun 27,"['Taylor, Lewis', 'Vasudevan, Sridhar R.', 'Jones, Chris I.', 'Gibbins, Jonathan M.', 'Churchill, Grant C.', 'Campbell, R. Duncan', 'Coxon, Carmen H.']",PLoS One,,,True
7b96a98291fe154a1abf59e93e00f52ac9ac230b,PMC,Alphavirus-Based Vaccines,http://dx.doi.org/10.3390/v6062392,PMC4074933,24937089,CC BY,"Alphavirus vectors have demonstrated high levels of transient heterologous gene expression both in vitro and in vivo and, therefore, possess attractive features for vaccine development. The most commonly used delivery vectors are based on three single-stranded encapsulated alphaviruses, namely Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus. Alphavirus vectors have been applied as replication-deficient recombinant viral particles and, more recently, as replication-proficient particles. Moreover, in vitro transcribed RNA, as well as layered DNA vectors have been applied for immunization. A large number of highly immunogenic viral structural proteins expressed from alphavirus vectors have elicited strong neutralizing antibody responses in multispecies animal models. Furthermore, immunization studies have demonstrated robust protection against challenges with lethal doses of virus in rodents and primates. Similarly, vaccination with alphavirus vectors expressing tumor antigens resulted in prophylactic protection against challenges with tumor-inducing cancerous cells. As certain alphaviruses, such as Chikungunya virus, have been associated with epidemics in animals and humans, attention has also been paid to the development of vaccines against alphaviruses themselves. Recent progress in alphavirus vector development and vaccine technology has allowed conducting clinical trials in humans.",2014 Jun 16,"Lundstrom, Kenneth",Viruses,,,True
e5b3fc64db01648fa06f51f1cde95ff3d0925607,PMC,Influenza and Other Respiratory Viruses Involved in Severe Acute Respiratory Disease in Northern Italy during the Pandemic and Postpandemic Period (2009–2011),http://dx.doi.org/10.1155/2014/241298,PMC4075074,25013770,CC BY,"Since 2009 pandemic, international health authorities recommended monitoring severe and complicated cases of respiratory disease, that is, severe acute respiratory infection (SARI) and acute respiratory distress syndrome (ARDS). We evaluated the proportion of SARI/ARDS cases and deaths due to influenza A(H1N1)pdm09 infection and the impact of other respiratory viruses during pandemic and postpandemic period (2009–2011) in northern Italy; additionally we searched for unknown viruses in those cases for which diagnosis remained negative. 206 respiratory samples were collected from SARI/ARDS cases and analyzed by real-time RT-PCR/PCR to investigate influenza viruses and other common respiratory pathogens; also, a virus discovery technique (VIDISCA-454) was applied on those samples tested negative to all pathogens. Influenza A(H1N1)pdm09 virus was detected in 58.3% of specimens, with a case fatality rate of 11.3%. The impact of other respiratory viruses was 19.4%, and the most commonly detected viruses were human rhinovirus/enterovirus and influenza A(H3N2). VIDISCA-454 enabled the identification of one previously undiagnosed measles infection. Nearly 22% of SARI/ARDS cases did not obtain a definite diagnosis. In clinical practice, great efforts should be dedicated to improving the diagnosis of severe respiratory disease; the introduction of innovative molecular technologies, as VIDISCA-454, will certainly help in reducing such “diagnostic gap.”",2014 Jun 12,"['Pariani, Elena', 'Martinelli, Marianna', 'Canuti, Marta', 'Jazaeri Farsani, Seyed Mohammad', 'Oude Munnink, Bas B.', 'Deijs, Martin', 'Tanzi, Elisabetta', 'Zanetti, Alessandro', 'van der Hoek, Lia', 'Amendola, Antonella']",Biomed Res Int,,,True
ba502a88e3f83aa9e3d5edd649970db6da85c5bf,PMC,The role of CXCL10 in the pathogenesis of experimental septic shock,http://dx.doi.org/10.1186/cc13902,PMC4075230,24890566,CC BY,"INTRODUCTION: The chemokine CXCL10 is produced during infection and inflammation to activate the chemokine receptor CXCR3, an important regulator of lymphocyte trafficking and activation. The goal of this study was to assess the contributions of CXCL10 to the pathogenesis of experimental septic shock in mice. METHODS: Septic shock was induced by cecal ligation and puncture (CLP) in mice resuscitated with lactated Ringer’s solution and, in some cases, the broad spectrum antibiotic Primaxin. Studies were performed in CXCL10 knockout mice and mice treated with anti-CXCL10 immunoglobulin G (IgG). Endpoints included leukocyte trafficking and activation, core body temperature, plasma cytokine concentrations, bacterial clearance and survival. RESULTS: CXCL10 was present at high concentrations in plasma and peritoneal cavity during CLP-induced septic shock. Survival was significantly improved in CXCL10 knockout (CXCL10KO) mice and mice treated with anti-CXCL10 IgG compared to controls. CXCL10KO mice and mice treated with anti-CXCL10 IgG showed attenuated hypothermia, lower concentrations of interleukin-6 (IL-6) and macrophage inhibitory protein-2 (MIP-2) in plasma and lessened natural killer (NK) cell activation compared to control mice. Compared to control mice, bacterial burden in blood and lungs was lower in CXCL10-deficient mice but not in mice treated with anti-CXCL10 IgG. Treatment of mice with anti-CXCL10 IgG plus fluids and Primaxin at 2 or 6 hours after CLP significantly improved survival compared to mice treated with non-specific IgG under the same conditions. CONCLUSIONS: CXCL10 plays a role in the pathogenesis of CLP-induced septic shock and could serve as a therapeutic target during the acute phase of septic shock.",2014 Jun 2,"['Herzig, Daniela S', 'Luan, Liming', 'Bohannon, Julia K', 'Toliver-Kinsky, Tracy E', 'Guo, Yin', 'Sherwood, Edward R']",Crit Care,,,True
2a3a08fcd21eb4e6ed6251960b7e1e6cf1a7f18a,PMC,"Pandemic clinical case definitions are non-specific: multiple respiratory viruses circulating in the early phases of the 2009 influenza pandemic in New South Wales, Australia",http://dx.doi.org/10.1186/1743-422X-11-113,PMC4076060,24942807,CC BY,"BACKGROUND: During the early phases of the 2009 pandemic, subjects with influenza-like illness only had laboratory testing specific for the new A(H1N1)pdm09 virus. FINDINGS: Between 25(th) May and 7(th) June 2009, during the pandemic CONTAIN phase, A(H1N1)pdm09 virus was detected using nucleic acid tests in only 56 of 1466 (3.8%) samples meeting the clinical case definition required for A(H1N1)pdm09 testing. Two hundred and fifty-five randomly selected A(H1N1)pdm09 virus-negative samples were tested for other respiratory viruses using a real-time multiplex PCR assay. Of the 255 samples tested, 113 (44.3%) had other respiratory viruses detected: rhinoviruses 63.7%, seasonal influenza A 17.6%, respiratory syncytial virus 7.9%, human metapneumovirus 5.3%, parainfluenzaviruses 4.4%, influenza B virus 4.4%, and enteroviruses 0.8%. Viral co-infections were present in 4.3% of samples. CONCLUSIONS: In the very early stages of a new pandemic, limiting testing to only the novel virus will miss other clinically important co-circulating respiratory pathogens.",2014 Jun 18,"['Ratnamohan, Vigneswary Mala', 'Taylor, Janette', 'Zeng, Frank', 'McPhie, Kenneth', 'Blyth, Christopher C', 'Adamson, Sheena', 'Kok, Jen', 'Dwyer, Dominic E']",Virol J,,,True
9c2755f8ae42badb521b1c6afcb99874d21657e5,PMC,Comparison and Analysis of Biological Agent Category Lists Based On Biosafety and Biodefense,http://dx.doi.org/10.1371/journal.pone.0101163,PMC4076228,24979754,CC BY,"Biological agents pose a serious threat to human health, economic development, social stability and even national security. The classification of biological agents is a basic requirement for both biosafety and biodefense. We compared and analyzed the Biological Agent Laboratory Biosafety Category list and the defining criteria according to the World Health Organization (WHO), the National Institutes of Health (NIH), the European Union (EU) and China. We also compared and analyzed the Biological Agent Biodefense Category list and the defining criteria according to the Centers for Disease Control and Prevention (CDC) of the United States, the EU and Russia. The results show some inconsistencies among or between the two types of category lists and criteria. We suggest that the classification of biological agents based on laboratory biosafety should reduce the number of inconsistencies and contradictions. Developing countries should also produce lists of biological agents to direct their development of biodefense capabilities.To develop a suitable biological agent list should also strengthen international collaboration and cooperation.",2014 Jun 30,"['Tian, Deqiao', 'Zheng, Tao']",PLoS One,,,True
25b38d2f44283253d1e8d320c8389c069c5ae906,PMC,HIV-1 and Its gp120 Inhibits the Influenza A(H1N1)pdm09 Life Cycle in an IFITM3-Dependent Fashion,http://dx.doi.org/10.1371/journal.pone.0101056,PMC4076258,24978204,CC BY,"HIV-1-infected patients co-infected with A(H1N1)pdm09 surprisingly presented benign clinical outcome. The knowledge that HIV-1 changes the host homeostatic equilibrium, which may favor the patient resistance to some co-pathogens, prompted us to investigate whether HIV-1 infection could influence A(H1N1)pdm09 life cycle in vitro. We show here that exposure of A(H1N1)pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content, resulting in a decrease in influenza replication. This event was dependent on toll-like receptor 2 and 4. Moreover, knockdown of IFITM3 prevented HIV-1 ability to inhibit A(H1N1)pdm09 replication. HIV-1 infection also increased IFITM3 levels in human primary macrophages by almost 100%. Consequently, the arrival of influenza ribonucleoproteins (RNPs) to nucleus of macrophages was inhibited, as evaluated by different approaches. Reduction of influenza RNPs entry into the nucleus tolled A(H1N1)pdm09 life cycle in macrophages earlier than usual, limiting influenza's ability to induce TNF-α. As judged by analysis of the influenza hemagglutin (HA) gene from in vitro experiments and from samples of HIV-1/A(H1N1)pdm09 co-infected individuals, the HIV-1-induced reduction of influenza replication resulted in delayed viral evolution. Our results may provide insights on the mechanisms that may have attenuated the clinical course of Influenza in HIV-1/A(H1N1)pdm09 co-infected patients during the recent influenza form 2009/2010.",2014 Jun 30,"['Mesquita, Milene', 'Fintelman-Rodrigues, Natalia', 'Sacramento, Carolina Q.', 'Abrantes, Juliana L.', 'Costa, Eduardo', 'Temerozo, Jairo R.', 'Siqueira, Marilda M.', 'Bou-Habib, Dumith Chequer', 'Souza, Thiago Moreno L.']",PLoS One,,,True
c66be1e891285a777b15ba49e685452fed6ee837,PMC,Differences in the tissue tropism to chicken oviduct epithelial cells between avian coronavirus IBV strains QX and B1648 are not related to the sialic acid binding properties of their spike proteins,http://dx.doi.org/10.1186/1297-9716-45-67,PMC4076756,24928425,CC BY,"The avian coronavirus (AvCoV) infectious bronchitis virus (IBV) is a major poultry pathogen. A characteristic feature of IBV is the occurrence of many different strains belonging to different serotypes, which makes a complete control of the disease by vaccinations a challenging task. Reasons for differences in the tissue tropism and pathogenicity between IBV strains, e.g. a predilection for the kidneys or the oviduct are still an open question. Strains of the QX genotype have been major pathogens in poultry flocks in Asia, Europe and other parts of the world. They are the cause of severe problems with kidney disease and reproductive tract disorders. We analysed infectivity and binding properties of the QX strain and compared them with those of the nephropathogenic strain B1648. As most IBV strains do not infect permanent cell lines and show infection only in primary chicken cells of the target organs, we developed a culture system for chicken oviduct explants. The epithelial cells of the oviduct showed a high susceptibility to infection by the QX strain and were almost resistant to infection by the nephropathogenic B1648 strain. Binding tests with isolated primary oviduct epithelial cells and soluble S1 proteins revealed that S1 proteins of two IBV strains bound with the same efficiency to oviduct epithelial cells. This attachment was sialic acid dependent, indicating that the sugar binding property of IBV spike proteins is not the limiting factor for differences in infection efficiency for the oviduct of the corresponding viruses.",2014 Jun 14,"['Mork, Ann-Kathrin', 'Hesse, Martina', 'Abd El Rahman, Sahar', 'Rautenschlein, Silke', 'Herrler, Georg', 'Winter, Christine']",Vet Res,,,True
13582a5cf358e261c5f432ea1abc513ae637e3dc,PMC,Differences in the tissue tropism to chicken oviduct epithelial cells between avian coronavirus IBV strains QX and B1648 are not related to the sialic acid binding properties of their spike proteins,http://dx.doi.org/10.1186/1297-9716-45-67,PMC4076756,24928425,CC BY,"The avian coronavirus (AvCoV) infectious bronchitis virus (IBV) is a major poultry pathogen. A characteristic feature of IBV is the occurrence of many different strains belonging to different serotypes, which makes a complete control of the disease by vaccinations a challenging task. Reasons for differences in the tissue tropism and pathogenicity between IBV strains, e.g. a predilection for the kidneys or the oviduct are still an open question. Strains of the QX genotype have been major pathogens in poultry flocks in Asia, Europe and other parts of the world. They are the cause of severe problems with kidney disease and reproductive tract disorders. We analysed infectivity and binding properties of the QX strain and compared them with those of the nephropathogenic strain B1648. As most IBV strains do not infect permanent cell lines and show infection only in primary chicken cells of the target organs, we developed a culture system for chicken oviduct explants. The epithelial cells of the oviduct showed a high susceptibility to infection by the QX strain and were almost resistant to infection by the nephropathogenic B1648 strain. Binding tests with isolated primary oviduct epithelial cells and soluble S1 proteins revealed that S1 proteins of two IBV strains bound with the same efficiency to oviduct epithelial cells. This attachment was sialic acid dependent, indicating that the sugar binding property of IBV spike proteins is not the limiting factor for differences in infection efficiency for the oviduct of the corresponding viruses.",2014 Jun 14,"['Mork, Ann-Kathrin', 'Hesse, Martina', 'Abd El Rahman, Sahar', 'Rautenschlein, Silke', 'Herrler, Georg', 'Winter, Christine']",Vet Res,,,False
5752683f35a4f922c8a1a363c93dcae050b92b50,PMC,How to Reduce the Latent Social Risk of Disease: The Determinants of Vaccination against Rabies in Taiwan,http://dx.doi.org/10.3390/ijerph110605934,PMC4078556,24901413,CC BY,"To control the latent social risk of disease, the government usually spreads accurate information and attempts to improve the public’s attitude toward adopting prevention. However, these methods with the Knowledge, Attitudes, and Practices (KAP) model do not always work. Therefore, we used the theory of planned behavior (TPB) to understand dog owners’ behavior and distinguished the knowledge effect as objective knowledge (OK) and subjective knowledge (SK). A total of 310 dog owners completed a questionnaire based on our model. We employed structural equation modeling to verify the structural relationships and found three main results. First, our model was fit, and each path was significant. People with better attitudes, stronger subjective norms, and more perceptive behavioral control have stronger behavioral intention. Second, perceived behavioral control, not attitude, was the best predictive index in this model. Finally, on perceived behavioral control, subjective knowledge showed more influence than objective knowledge. We successfully extended TPB to explain the behavioral intention of dog owners and presented more workable recommendations. To reduce the latent social risk of disease, the government should not only address dog owners’ attitudes, but also their subjective norms and perceptive behavioral control. Indeed, perceptive behavioral control and SK showed the most influence in this model. It is implied that the self-efficacy of dog owners is the most important factor in such a behavior. Therefore, the government should focus on enhancing dog owners’ self-efficacy first while devoted to prevention activities.",2014 Jun 4,"['Ku-Yuan, Lee', 'Li-Chi, Lan', 'Jiun-Hao, Wang', 'Chen-Ling, Fang', 'Kun-Sun, Shiao']",Int J Environ Res Public Health,,,True
b6c62ca4653ef469da8a131bcd9fe168e439e3a3,PMC,A Comprehensive Phylogenetic and Structural Analysis of the Carcinoembryonic Antigen (CEA) Gene Family,http://dx.doi.org/10.1093/gbe/evu103,PMC4079198,24858421,CC BY,"The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin (Ig) superfamily and codes for a vast number of glycoproteins that differ greatly both in amino acid composition and function. The CEA family is divided into two groups, the carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) and the pregnancy-specific glycoproteins. The CEA family members are implicated in pleiotropic (patho)physiological functions including cell–cell adhesion, pregnancy, immunity, neovascularization, regulation of insulin homeostasis, and carcinogenesis. In general, the CEA-encoded proteins are composed of an extracellular region with Ig variable and constant-like domains and a cytoplasmic region containing signaling motifs. Of particular interest, the well-studied human and mouse CEA genes are arranged in clusters in a single chromosome. Taking into account this characteristic, we made an effort to reconstruct the evolutionary history of the CEA gene family. Toward this end, the publicly available genomes were searched extensively for CEA homologs. The domain organization of the retrieved protein sequences was analyzed, and, subsequently, comprehensive phylogenetic analyses of the entire length CEA homologous proteins were performed. A series of evolutionarily conserved amino acid residues, functionally important, were identified. The relative positioning of these residues on the modeled tertiary structure of novel CEA protein domains revealed that they are, also, spatially conserved. Furthermore, the chromosomal arrangement of CEA genes was examined, and it was found that the CEA genes are preserved in terms of position, transcriptional orientation, and number in all species under investigation.",2014 May 23,"['Pavlopoulou, Athanasia', 'Scorilas, Andreas']",Genome Biol Evol,,,True
4660da2a8603d28150c9d3de1a17c0333094087c,PMC,Histopathology of Pneumocystis carinii pneumonia in immunocompetent laboratory rats,http://dx.doi.org/10.3892/etm.2014.1732,PMC4079405,25009598,CC BY,"The occurrence of idiopathic pulmonary lesions in laboratory rats, characterized by lymphohistiocytic interstitial pneumonia with dense perivascular lymphoid cuffs, has been reported over the past decade. Although the term rat respiratory virus (RRV) was adopted to confer a putative viral etiology to the idiopathic pulmonary lesions, the etiology of this disease remains to be elucidated. Recently, inflammatory lesions have been observed in the lungs of immunocompetent laboratory rats similar to those previously described. Based on the latest evidence indicating that Pneumocystis carinii (P. carinii), and not putative RRV, causes infectious interstitial pneumonia in laboratory rats, the present study investigated whether the pulmonary lesions observed were caused by P. carinii infection. Male Sprague-Dawley rats, free of known pathogens, were introduced into a rat colony positive for RRV-type lesions. Routine histopathological examinations were performed on the rat lung tissues following exposure. The presence of Pneumocystis organisms was confirmed using Grocott’s methenamine silver (GMS) staining. At week 3 following introduction, a few small lymphoid aggregates were located adjacent to the edematous vascular sheath. By week 5, foci of dense perivascular lymphoid cuffing were observed. Multifocal lymphohistiocytic interstitial pneumonia and prominent lymphoid perivascular cuffs were observed between week 7 and 10. GMS staining confirmed the presence of Pneumocystis cysts. Thus, the results of the present study demonstrated that P. carinii caused lymphohistiocytic interstitial pneumonia in a group of laboratory rats. The observations strongly support the conclusion that P. carinii infection in immunocompetent laboratory rats causes the lung lesions that were previously attributed to RRV.",2014 Aug 26,"['KIM, HYUN-SOO', 'DO, SUNG-IM', 'KIM, YOUN WHA']",Exp Ther Med,,,True
ff77d5ebc39274bb7729f2b5261bca574bdfd6a8,PMC,"Prevalence and Genetic Diversity Analysis of Human Coronavirus OC43 among Adult Patients with Acute Respiratory Infections in Beijing, 2012",http://dx.doi.org/10.1371/journal.pone.0100781,PMC4079595,24987849,CC BY,"To determine the prevalence, epidemiology and genetic diversity of human coronavirus OC43 (HCoV-OC43) among adult patients with acute respiratory infections (ARI) in Beijing,five hundred and fifty-nine nasopharyngeal swab samples were collected from adult patients with ARI in Beijing. The prevalence of HCoV-OC43 infection among these patients was assessed using two different OneStep reverse transcription polymerase chain reaction (RT-PCR) assays. The epidemiological profiles of the patients with HCoV-OC43 infection were described. Partial S and N genes of HCoV-OC43 circulating strains were sequenced followed by phylogenetic analysis and amino acid alignment. Our results showed that the prevalence of HCoV-OC43 infection was 12.52% (95% CI: 9.78–15.26%), and the epidemic peak occurred in autumn. Fifty partial S and 40 partial N fragments were obtained from these patients. Phylogenetic analysis based on neighbour-joining method showed that at least three distinct clusters (A, B, C/D) of HCoV-OC43 strains were circulating among adult patients with ARI in Beijing. In addition, some novel unique clusters (UNT) of HCoV-OC43 were found in the S- and N-based phylogenetic trees. Furthermore, consensus amino acids substitutes for each cluster were also found after alignment of partial S or N sequence coding region in this study. In conclusion, we herein describe the prevalence of HCoV-OC43 among adult patients and provide substantial evidence for the genetic diversity of HCoV-OC43 circulating in Beijing.",2014 Jul 2,"['Hu, Qin', 'Lu, Roujian', 'Peng, Kun', 'Duan, Xijie', 'Wang, Yanqun', 'Zhao, Yanjie', 'Wang, Wen', 'Lou, Yongliang', 'Tan, Wenjie']",PLoS One,,,True
36eedeee8fd40eda2f7f1d0c0cb0e2a4971439a6,PMC,"After Malaria Is Controlled, What's Next?†",http://dx.doi.org/10.4269/ajtmh.14-0056,PMC4080571,24591436,CC BY,,2014 Jul 2,"Walker, David H.",Am J Trop Med Hyg,,,True
40ae6bae0a5f86ac9beb57de189ae3320875e22c,PMC,ERAD and how viruses exploit it,http://dx.doi.org/10.3389/fmicb.2014.00330,PMC4080680,25071743,CC BY,"Endoplasmic reticulum (ER)-associated degradation (ERAD) is a universally important process among eukaryotic cells. ERAD is necessary to preserve cell integrity since the accumulation of defective proteins results in diseases associated with neurological dysfunction, cancer, and infections. This process involves recognition of misfolded or misassembled proteins that have been translated in association with ER membranes. Recognition of ERAD substrates leads to their extraction through the ER membrane (retrotranslocation or dislocation), ubiquitination, and destruction by cytosolic proteasomes. This review focuses on ERAD and its components as well as how viruses use this process to promote their replication and to avoid the immune response.",2014 Jul 3,"['Byun, Hyewon', 'Gou, Yongqiang', 'Zook, Adam', 'Lozano, Mary M.', 'Dudley, Jaquelin P.']",Front Microbiol,,,True
dcd7287d538d38848896654f8dd359f9adf94946,PMC,Advances in Diagnosis of Respiratory Diseases of Small Ruminants,http://dx.doi.org/10.1155/2014/508304,PMC4082846,25028620,CC BY,"Irrespective of aetiology, infectious respiratory diseases of sheep and goats contribute to 5.6 percent of the total diseases of small ruminants. These infectious respiratory disorders are divided into two groups: the diseases of upper respiratory tract, namely, nasal myiasis and enzootic nasal tumors, and diseases of lower respiratory tract, namely, peste des petits ruminants (PPR), parainfluenza, Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, caprine arthritis encephalitis virus, caseous lymphadenitis, verminous pneumonia, and many others. Depending upon aetiology, many of them are acute and fatal in nature. Early, rapid, and specific diagnosis of such diseases holds great importance to reduce the losses. The advanced enzyme-linked immunosorbent assays (ELISAs) for the detection of antigen as well as antibodies directly from the samples and molecular diagnostic assays along with microsatellites comprehensively assist in diagnosis as well as treatment and epidemiological studies. The present review discusses the advancements made in the diagnosis of common infectious respiratory diseases of sheep and goats. It would update the knowledge and help in adapting and implementing appropriate, timely, and confirmatory diagnostic procedures. Moreover, it would assist in designing appropriate prevention protocols and devising suitable control strategies to overcome respiratory diseases and alleviate the economic losses.",2014 Jun 15,"['Chakraborty, Sandip', 'Kumar, Amit', 'Tiwari, Ruchi', 'Rahal, Anu', 'Malik, Yash', 'Dhama, Kuldeep', 'Pal, Amar', 'Prasad, Minakshi']",Vet Med Int,,,True
af6cc29d9bc7f9d84ded3d7ad30509a945e425d3,PMC,Metagenomic analysis of a sample from a patient with respiratory tract infection reveals the presence of a γ-papillomavirus,http://dx.doi.org/10.3389/fmicb.2014.00347,PMC4086198,25071755,CC BY,"Previously unknown or unexpected pathogens may be responsible for that proportion of respiratory diseases in which a causative agent cannot be identified. The application of broad-spectrum, sequence independent virus discovery techniques may be useful to reduce this proportion and widen our knowledge about respiratory pathogens. Thanks to the availability of high-throughput sequencing (HTS) technology, it became today possible to detect viruses which are present at a very low load, but the clinical relevance of those viruses must be investigated. In this study we used VIDISCA-454, a restriction enzyme based virus discovery method that utilizes Roche 454 HTS system, on a nasal swab collected from a subject with respiratory complaints. A γ-papillomavirus was detected (complete genome: 7142 bp) and its role in disease was investigated. Respiratory samples collected both during the acute phase of the illness and 2 weeks after full recovery contained the virus. The patient presented antibodies directed against the virus but there was no difference between IgG levels in blood samples collected during the acute phase and 2 weeks after full recovery. We therefore concluded that the detected γ-papillomavirus is unlikely to be the causative agent of the respiratory complaints and its presence in the nose of the patient is not related to the disease. Although HTS based virus discovery techniques proved their great potential as a tool to clarify the etiology of some infectious diseases, the obtained information must be subjected to cautious interpretations. This study underlines the crucial importance of performing careful investigations on viruses identified when applying sensitive virus discovery techniques, since the mere identification of a virus and its presence in a clinical sample are not satisfactory proofs to establish a causative link with a disease.",2014 Jul 8,"['Canuti, Marta', 'Deijs, Martin', 'Jazaeri Farsani, Seyed M.', 'Holwerda, Melle', 'Jebbink, Maarten F.', 'de Vries, Michel', 'van Vugt, Saskia', 'Brugman, Curt', 'Verheij, Theo', 'Lammens, Christine', 'Goossens, Herman', 'Loens, Katherine', 'Ieven, Margareta', 'van der Hoek, Lia']",Front Microbiol,,,True
0542a6ae26f57a5ffa35dcfebdec5004ff45688c,PMC,Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies,http://dx.doi.org/10.1371/journal.pone.0101785,PMC4086938,25004134,CC0,"BACKGROUND: Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients. METHODS AND FINDINGS: Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1–3) and 6 days (IQR 4–10) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4–7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5–26.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons. CONCLUSIONS: Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic influenza epidemics globally. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: FLU 002- NCT01056354, FLU 003- NCT01056185.",2014 Jul 8,"['Lynfield, Ruth', 'Davey, Richard', 'Dwyer, Dominic E.', 'Losso, Marcelo H.', 'Wentworth, Deborah', 'Cozzi-Lepri, Alessandro', 'Herman-Lamin, Kathy', 'Cholewinska, Grazyna', 'David, Daniel', 'Kuetter, Stefan', 'Ternesgen, Zelalem', 'Uyeki, Timothy M.', 'Lane, H. Clifford', 'Lundgren, Jens', 'Neaton, James D.', None]",PLoS One,,,True
403d1861771bf1e5e3625b0f86247d7134c3873d,PMC,Pandemic preparedness: perceptions of vulnerable migrants in Thailand towards WHO-recommended non-pharmaceutical interventions: a cross-sectional study,http://dx.doi.org/10.1186/1471-2458-14-665,PMC4090173,24973943,CC BY,"BACKGROUND: Non-pharmaceutical interventions (NPIs) constituted the principal public health response to the previous influenza A (H1N1) 2009 pandemic and are one key area of ongoing preparation for future pandemics. Thailand is an important point of focus in terms of global pandemic preparedness and response due to its role as the major transportation hub for Southeast Asia, the endemic presence of multiple types of influenza, and its role as a major receiving country for migrants. Our aim was to collect information about vulnerable migrants’ perceptions of and ability to implement NPIs proposed by the WHO. We hope that this information will help us to gauge the capacity of this population to engage in pandemic preparedness and response efforts, and to identify potential barriers to NPI effectiveness. METHODS: A cross-sectional survey was performed. The study was conducted during the influenza H1N1 2009 pandemic and included 801 migrant participants living in border areas thought to be high risk by the Thailand Ministry of Public Health. Data were collected by Migrant Community Health Workers using a 201-item interviewer-assisted questionnaire. Univariate descriptive analyses were conducted. RESULTS: With the exception of border measures, to which nearly all participants reported they would be adherent, attitudes towards recommended NPIs were generally negative or uncertain. Other potential barriers to NPI implementation include limited experience applying these interventions (e.g., using a thermometer, wearing a face mask) and inadequate hand washing and household disinfection practices. CONCLUSIONS: Negative or ambivalent attitudes towards NPIs combined with other barriers identified suggest that vulnerable migrants in Thailand have a limited capacity to participate in pandemic preparedness efforts. This limited capacity likely puts migrants at risk of propagating the spread of a pandemic virus. Coordinated risk communication and public education are potential strategies that may reduce barriers to individual NPI implementation.",2014 Jun 28,"['Hickey, Jason', 'Gagnon, Anita J', 'Jitthai, Nigoon']",BMC Public Health,,,True
3b2a2a17eb789fee6c46ff6cdc7b6e794f7d545c,PMC,Epidemic Surveillance Using an Electronic Medical Record: An Empiric Approach to Performance Improvement,http://dx.doi.org/10.1371/journal.pone.0100845,PMC4090236,25006878,CC0,"BACKGROUNDS: Electronic medical records (EMR) form a rich repository of information that could benefit public health. We asked how structured and free-text narrative EMR data should be combined to improve epidemic surveillance for acute respiratory infections (ARI). METHODS: Eight previously characterized ARI case detection algorithms (CDA) were applied to historical EMR entries to create authentic time series of daily ARI case counts (background). An epidemic model simulated influenza cases (injection). From the time of the injection, cluster-detection statistics were applied daily on paired background+injection (combined) and background-only time series. This cycle was then repeated with the injection shifted to each week of the evaluation year. We computed: a) the time from injection to the first statistical alarm uniquely found in the combined dataset (Detection Delay); b) how often alarms originated in the background-only dataset (false-alarm rate, or FAR); and c) the number of cases found within these false alarms (Caseload). For each CDA, we plotted the Detection Delay as a function of FAR or Caseload, over a broad range of alarm thresholds. RESULTS: CDAs that combined text analyses seeking ARI symptoms in clinical notes with provider-assigned diagnostic codes in order to maximize the precision rather than the sensitivity of case-detection lowered Detection Delay at any given FAR or Caseload. CONCLUSION: An empiric approach can guide the integration of EMR data into case-detection methods that improve both the timeliness and efficiency of epidemic detection.",2014 Jul 9,"['Zheng, Hongzhang', 'Gaff, Holly', 'Smith, Gary', 'DeLisle, Sylvain']",PLoS One,,,True
e023845ba693ca1f8667d37d40b02626a6c2ecd5,PMC,On the Use of Human Mobility Proxies for Modeling Epidemics,http://dx.doi.org/10.1371/journal.pcbi.1003716,PMC4091706,25010676,CC BY,"Human mobility is a key component of large-scale spatial-transmission models of infectious diseases. Correctly modeling and quantifying human mobility is critical for improving epidemic control, but may be hindered by data incompleteness or unavailability. Here we explore the opportunity of using proxies for individual mobility to describe commuting flows and predict the diffusion of an influenza-like-illness epidemic. We consider three European countries and the corresponding commuting networks at different resolution scales, obtained from (i) official census surveys, (ii) proxy mobility data extracted from mobile phone call records, and (iii) the radiation model calibrated with census data. Metapopulation models defined on these countries and integrating the different mobility layers are compared in terms of epidemic observables. We show that commuting networks from mobile phone data capture the empirical commuting patterns well, accounting for more than 87% of the total fluxes. The distributions of commuting fluxes per link from mobile phones and census sources are similar and highly correlated, however a systematic overestimation of commuting traffic in the mobile phone data is observed. This leads to epidemics that spread faster than on census commuting networks, once the mobile phone commuting network is considered in the epidemic model, however preserving to a high degree the order of infection of newly affected locations. Proxies' calibration affects the arrival times' agreement across different models, and the observed topological and traffic discrepancies among mobility sources alter the resulting epidemic invasion patterns. Results also suggest that proxies perform differently in approximating commuting patterns for disease spread at different resolution scales, with the radiation model showing higher accuracy than mobile phone data when the seed is central in the network, the opposite being observed for peripheral locations. Proxies should therefore be chosen in light of the desired accuracy for the epidemic situation under study.",2014 Jul 10,"['Tizzoni, Michele', 'Bajardi, Paolo', 'Decuyper, Adeline', 'Kon Kam King, Guillaume', 'Schneider, Christian M.', 'Blondel, Vincent', 'Smoreda, Zbigniew', 'González, Marta C.', 'Colizza, Vittoria']",PLoS Comput Biol,,,True
0a7a6b0343a8760e62e7b69c3eacae5c9d1eddc7,PMC,On the Use of Human Mobility Proxies for Modeling Epidemics,http://dx.doi.org/10.1371/journal.pcbi.1003716,PMC4091706,25010676,CC BY,"Human mobility is a key component of large-scale spatial-transmission models of infectious diseases. Correctly modeling and quantifying human mobility is critical for improving epidemic control, but may be hindered by data incompleteness or unavailability. Here we explore the opportunity of using proxies for individual mobility to describe commuting flows and predict the diffusion of an influenza-like-illness epidemic. We consider three European countries and the corresponding commuting networks at different resolution scales, obtained from (i) official census surveys, (ii) proxy mobility data extracted from mobile phone call records, and (iii) the radiation model calibrated with census data. Metapopulation models defined on these countries and integrating the different mobility layers are compared in terms of epidemic observables. We show that commuting networks from mobile phone data capture the empirical commuting patterns well, accounting for more than 87% of the total fluxes. The distributions of commuting fluxes per link from mobile phones and census sources are similar and highly correlated, however a systematic overestimation of commuting traffic in the mobile phone data is observed. This leads to epidemics that spread faster than on census commuting networks, once the mobile phone commuting network is considered in the epidemic model, however preserving to a high degree the order of infection of newly affected locations. Proxies' calibration affects the arrival times' agreement across different models, and the observed topological and traffic discrepancies among mobility sources alter the resulting epidemic invasion patterns. Results also suggest that proxies perform differently in approximating commuting patterns for disease spread at different resolution scales, with the radiation model showing higher accuracy than mobile phone data when the seed is central in the network, the opposite being observed for peripheral locations. Proxies should therefore be chosen in light of the desired accuracy for the epidemic situation under study.",2014 Jul 10,"['Tizzoni, Michele', 'Bajardi, Paolo', 'Decuyper, Adeline', 'Kon Kam King, Guillaume', 'Schneider, Christian M.', 'Blondel, Vincent', 'Smoreda, Zbigniew', 'González, Marta C.', 'Colizza, Vittoria']",PLoS Comput Biol,,,False
e952843f8bdc91e48ca6fa5fa94d53abdfb63ff7,PMC,The Ubiquitin-Conjugating System: Multiple Roles in Viral Replication and Infection,http://dx.doi.org/10.3390/cells3020386,PMC4092849,24805990,CC BY,"Through the combined action of ubiquitinating and deubiquitinating enzymes, conjugation of ubiquitin to a target protein acts as a reversible post-translational modification functionally similar to phosphorylation. Indeed, ubiquitination is more and more recognized as a central process for the fine regulation of many cellular pathways. Due to their nature as obligate intracellular parasites, viruses rely on the most conserved host cell machineries for their own replication. Thus, it is not surprising that members from almost every viral family are challenged by ubiquitin mediated mechanisms in different steps of their life cycle and have evolved in order to by-pass or exploit the cellular ubiquitin conjugating system to maximize their chance to establish a successful infection. In this review we will present several examples of the complex interplay that links viruses and the ubiquitin conjugation machinery, with a special focus on the mechanisms evolved by the human immunodeficiency virus to escape from cellular restriction factors and to exit from infected cells.",2014 May 6,"['Calistri, Arianna', 'Munegato, Denis', 'Carli, Ilaria', 'Parolin, Cristina', 'Palù, Giorgio']",Cells,,,True
2de3df4bc6bfab602038165ccb45368768071956,PMC,Medical relevance of UK-funded non-human primate research published from January 1997 to July 2012,http://dx.doi.org/10.1177/0141076814530686,PMC4093757,24739383,CC BY,"In 2012, the Bateson Review of research using non-human primates (NHPs) recommended the commissioning of a working group to identify and follow-up the results of UK-funded NHP research of potential benefit for human health (Recommendation 4), but the Medical Research Council (MRC) has postponed implementation of the recommendation. Information on results and potential benefits of NHP research therefore remains unavailable. To fill this gap in knowledge, this study identified all published NHP research studies funded by the MRC, Wellcome Trust and Biotechnology and Biological Sciences Research Council (BBSRC) from January 1997 to July 2012 and assessed full texts for medical relevance. In total, 284 papers were identified, of which 51 (18%) involved invasive NHP research, compared to 176 (61%) which used NHP tissue and cell lines, indicating a shift in research emphasis from invasive whole animal to cell-based research. Of these studies, 98 (35%) were medically relevant, of which 22 had potential therapeutic or public health applications. The relatively low proportion of medical studies together with the small number of applied studies raises questions over the level of investment in medical research and the effectiveness of knowledge transfer from basic to applied research. Implementation of the Bateson Review’s Recommendation 4 would address these questions.",2014 Jul,"Moore, Edward",J R Soc Med,,,True
9cdbf5aaebee9f6b33cb9fbbdcd1a68d53727289,PMC,CXCR3 modulates glial accumulation and activation in cuprizone-induced demyelination of the central nervous system,http://dx.doi.org/10.1186/1742-2094-11-109,PMC4096537,24930935,CC BY,"BACKGROUND: The functional state of glial cells, like astrocytes and microglia, critically modulates the course of neuroinflammatory and neurodegenerative diseases and can have both detrimental and beneficial effects. Glial cell function is tightly controlled by cellular interactions in which cytokines are important messengers. Recent studies provide evidence that in particular chemokines are important modulators of glial cell function. During the course of CNS diseases like multiple sclerosis or Alzheimer’s disease, and in the corresponding animal models, the chemokines CXCL9 and CXCL10 are abundantly expressed at sites of glial activation, arguing for an important role of these chemokines and their corresponding receptor CXCR3 in glial activation. To clarify the role of this chemokine system in glial cell activation, we characterized the impact of CXCR3 on glial activation in a model of toxic demyelination in which glial activation without a prominent influx of hematogenous cells is prototypical. METHODS: We investigated the impact of CXCR3 on cuprizone-induced demyelination, comparing CXCR3-deficient mice with wild type controls. The clinical course during cuprizone feeding was documented for five weeks and for the subsequent four days withdrawal of the cuprizone diet (5.5 weeks). Glial activation was characterized using histological, histomorphometric and phenotypic analysis. Molecular analysis for (de)myelination and neuroinflammation was applied to characterize the effect of cuprizone on CXCR3-deficient mice and control animals. RESULTS: CXCR3-deficient mice displayed a milder clinical course during cuprizone feeding and a more rapid body weight recovery after offset of diet. In the CNS, CXCR3 deficiency significantly attenuated the accumulation and activation of microglia and astrocytes. Moreover, a deficiency of CXCR3 reduced the expression of the microglial activation markers CD45 and CD11b. Compared to controls, we observed a vast reduction of RNA levels for proinflammatory cytokines and chemokines like Ccl2, Cxcl10, Tnf and Il6 within the CNS of cuprizone-treated mice. Lastly, CXCR3 deficiency had no major effects on the course of demyelination during cuprizone feeding. CONCLUSIONS: The CXCR3 chemokine system is critically involved in the intrinsic glial activation during cuprizone-induced demyelination, which significantly modulates the distribution of glial cells and the local cytokine milieu.",2014 Jun 16,"['Krauthausen, Marius', 'Saxe, Simon', 'Zimmermann, Julian', 'Emrich, Michael', 'Heneka, Michael T', 'Müller, Marcus']",J Neuroinflammation,,,True
85e67a0122ea002985fd0e498a7f94df64957701,PMC,The use of the temporal scan statistic to detect methicillin-resistant Staphylococcus aureus clusters in a community hospital,http://dx.doi.org/10.1186/1471-2334-14-375,PMC4097048,25005247,CC BY,"BACKGROUND: In healthcare facilities, conventional surveillance techniques using rule-based guidelines may result in under- or over-reporting of methicillin-resistant Staphylococcus aureus (MRSA) outbreaks, as these guidelines are generally unvalidated. The objectives of this study were to investigate the utility of the temporal scan statistic for detecting MRSA clusters, validate clusters using molecular techniques and hospital records, and determine significant differences in the rate of MRSA cases using regression models. METHODS: Patients admitted to a community hospital between August 2006 and February 2011, and identified with MRSA > 48 hours following hospital admission, were included in this study. Between March 2010 and February 2011, MRSA specimens were obtained for spa typing. MRSA clusters were investigated using a retrospective temporal scan statistic. Tests were conducted on a monthly scale and significant clusters were compared to MRSA outbreaks identified by hospital personnel. Associations between the rate of MRSA cases and the variables year, month, and season were investigated using a negative binomial regression model. RESULTS: During the study period, 735 MRSA cases were identified and 167 MRSA isolates were spa typed. Nine different spa types were identified with spa type 2/t002 (88.6%) the most prevalent. The temporal scan statistic identified significant MRSA clusters at the hospital (n = 2), service (n = 16), and ward (n = 10) levels (P ≤ 0.05). Seven clusters were concordant with nine MRSA outbreaks identified by hospital staff. For the remaining clusters, seven events may have been equivalent to true outbreaks and six clusters demonstrated possible transmission events. The regression analysis indicated years 2009–2011, compared to 2006, and months March and April, compared to January, were associated with an increase in the rate of MRSA cases (P ≤ 0.05). CONCLUSIONS: The application of the temporal scan statistic identified several MRSA clusters that were not detected by hospital personnel. The identification of specific years and months with increased MRSA rates may be attributable to several hospital level factors including the presence of other pathogens. Within hospitals, the incorporation of the temporal scan statistic to standard surveillance techniques is a valuable tool for healthcare workers to evaluate surveillance strategies and aid in the identification of MRSA clusters.",2014 Jul 8,"['Faires, Meredith C', 'Pearl, David L', 'Ciccotelli, William A', 'Berke, Olaf', 'Reid-Smith, Richard J', 'Weese, J Scott']",BMC Infect Dis,,,True
e9f9bb005036503310d511566fbfc6b1a82d8fdd,PMC,Substitution at Aspartic Acid 1128 in the SARS Coronavirus Spike Glycoprotein Mediates Escape from a S2 Domain-Targeting Neutralizing Monoclonal Antibody,http://dx.doi.org/10.1371/journal.pone.0102415,PMC4097068,25019613,CC BY,"The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is the etiological agent for the infectious disease, SARS, which first emerged 10 years ago. SARS-CoV is a zoonotic virus that has crossed the species barriers to infect humans. Bats, which harbour a diverse pool of SARS-like CoVs (SL-CoVs), are believed to be the natural reservoir. The SARS-CoV surface Spike (S) protein is a major antigenic determinant in eliciting neutralizing antibody production during SARS-CoV infection. In our previous work, we showed that a panel of murine monoclonal antibodies (mAbs) that target the S2 subunit of the S protein are capable of neutralizing SARS-CoV infection in vitro (Lip KM et al, J Virol. 2006 Jan; 80(2): 941–50). In this study, we report our findings on the characterization of one of these mAbs, known as 1A9, which binds to the S protein at a novel epitope within the S2 subunit at amino acids 1111–1130. MAb 1A9 is a broadly neutralizing mAb that prevents viral entry mediated by the S proteins of human and civet SARS-CoVs as well as bat SL-CoVs. By generating mutant SARS-CoV that escapes the neutralization by mAb 1A9, the residue D1128 in S was found to be crucial for its interaction with mAb 1A9. S protein containing the substitution of D1128 with alanine (D1128A) exhibited a significant decrease in binding capability to mAb 1A9 compared to wild-type S protein. By using a pseudotyped viral entry assay, it was shown that the D1128A substitution in the escape virus allows it to overcome the viral entry blockage by mAb 1A9. In addition, the D1128A mutation was found to exert no effects on the S protein cell surface expression and incorporation into virion particles, suggesting that the escape virus retains the same viral entry property as the wild-type virus.",2014 Jul 14,"['Ng, Oi-Wing', 'Keng, Choong-Tat', 'Leung, Cynthia Sau-Wai', 'Peiris, J. S. Malik', 'Poon, Leo Lit Man', 'Tan, Yee-Joo']",PLoS One,,,True
fb0a470971165da64de3314623977282563c7a04,PMC,"Dissecting Virus Entry: Replication-Independent Analysis of Virus Binding, Internalization, and Penetration Using Minimal Complementation of β-Galactosidase",http://dx.doi.org/10.1371/journal.pone.0101762,PMC4099126,25025332,CC BY,"Studies of viral entry into host cells often rely on the detection of post-entry parameters, such as viral replication or the expression of a reporter gene, rather than on measuring entry per se. The lack of assays to easily detect the different steps of entry severely hampers the analysis of this key process in virus infection. Here we describe novel, highly adaptable viral entry assays making use of minimal complementation of the E. coli β-galactosidase in mammalian cells. Enzyme activity is reconstituted when a small intravirion peptide (α-peptide) is complementing the inactive mutant form ΔM15 of β-galactosidase. The method allows to dissect and to independently detect binding, internalization, and fusion of viruses during host cell entry. Here we use it to confirm and extend current knowledge on the entry process of two enveloped viruses: vesicular stomatitis virus (VSV) and murine hepatitis coronavirus (MHV).",2014 Jul 15,"['Burkard, Christine', 'Bloyet, Louis-Marie', 'Wicht, Oliver', 'van Kuppeveld, Frank J.', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.', 'Bosch, Berend Jan']",PLoS One,,,True
196eaa0045b36b7c0e56594ad4fbec1e8edd3e9c,PMC,"Dissecting Virus Entry: Replication-Independent Analysis of Virus Binding, Internalization, and Penetration Using Minimal Complementation of β-Galactosidase",http://dx.doi.org/10.1371/journal.pone.0101762,PMC4099126,25025332,CC BY,"Studies of viral entry into host cells often rely on the detection of post-entry parameters, such as viral replication or the expression of a reporter gene, rather than on measuring entry per se. The lack of assays to easily detect the different steps of entry severely hampers the analysis of this key process in virus infection. Here we describe novel, highly adaptable viral entry assays making use of minimal complementation of the E. coli β-galactosidase in mammalian cells. Enzyme activity is reconstituted when a small intravirion peptide (α-peptide) is complementing the inactive mutant form ΔM15 of β-galactosidase. The method allows to dissect and to independently detect binding, internalization, and fusion of viruses during host cell entry. Here we use it to confirm and extend current knowledge on the entry process of two enveloped viruses: vesicular stomatitis virus (VSV) and murine hepatitis coronavirus (MHV).",2014 Jul 15,"['Burkard, Christine', 'Bloyet, Louis-Marie', 'Wicht, Oliver', 'van Kuppeveld, Frank J.', 'Rottier, Peter J. M.', 'de Haan, Cornelis A. M.', 'Bosch, Berend Jan']",PLoS One,,,True
a87c83a672852a6d046357d68715f3c3c0cdf5b1,PMC,Viral Metagenomics on Animals as a Tool for the Detection of Zoonoses Prior to Human Infection?,http://dx.doi.org/10.3390/ijms150610377,PMC4100157,24918293,CC BY,"Many human viral infections have a zoonotic, i.e., wild or domestic animal, origin. Several zoonotic viruses are transmitted to humans directly via contact with an animal or indirectly via exposure to the urine or feces of infected animals or the bite of a bloodsucking arthropod. If a virus is able to adapt and replicate in its new human host, human-to-human transmissions may occur, possibly resulting in an epidemic, such as the A/H1N1 flu pandemic in 2009. Thus, predicting emerging zoonotic infections is an important challenge for public health officials in the coming decades. The recent development of viral metagenomics, i.e., the characterization of the complete viral diversity isolated from an organism or an environment using high-throughput sequencing technologies, is promising for the surveillance of such diseases and can be accomplished by analyzing the viromes of selected animals and arthropods that are closely in contact with humans. In this review, we summarize our current knowledge of viral diversity within such animals (in particular blood-feeding arthropods, wildlife and domestic animals) using metagenomics and present its possible future application for the surveillance of zoonotic and arboviral diseases.",2014 Jun 10,"['Temmam, Sarah', 'Davoust, Bernard', 'Berenger, Jean-Michel', 'Raoult, Didier', 'Desnues, Christelle']",Int J Mol Sci,,,True
e1c6885ff3cb7eded9abdbbebc8e486459265c95,PMC,Multiplex Evaluation of Influenza Neutralizing Antibodies with Potential Applicability to In-Field Serological Studies,http://dx.doi.org/10.1155/2014/457932,PMC4101955,25101305,CC BY,"The increased number of outbreaks of H5 and H7 LPAI and HPAI viruses in poultry has major public and animal health implications. The continuous rapid evolution of these subtypes and the emergence of new variants influence the ability to undertake effective surveillance. Retroviral pseudotypes bearing influenza haemagglutinin (HA) and neuraminidase (NA) envelope glycoproteins represent a flexible platform for sensitive, readily standardized influenza serological assays. We describe a multiplex assay for the study of neutralizing antibodies that are directed against both influenza H5 and H7 HA. This assay permits the measurement of neutralizing antibody responses against two antigenically distinct HAs in the same serum/plasma sample thus increasing the amount and quality of serological data that can be acquired from valuable sera. Sera obtained from chickens vaccinated with a monovalent H5N2 vaccine, chickens vaccinated with a bivalent H7N1/H5N9 vaccine, or turkeys naturally infected with an H7N3 virus were evaluated in this assay and the results correlated strongly with data obtained by HI assay. We show that pseudotypes are highly stable under basic cold-chain storage conditions and following multiple rounds of freeze-thaw. We propose that this robust assay may have practical utility for in-field serosurveillance and vaccine studies in resource-limited regions worldwide.",2014 Jul 3,"['Molesti, Eleonora', 'Wright, Edward', 'Terregino, Calogero', 'Rahman, Rafat', 'Cattoli, Giovanni', 'Temperton, Nigel J.']",J Immunol Res,,,True
9e3db9f0b5e4e5811a8b21576cb08297043ddb84,PMC,Antagonizing Interferon-Mediated Immune Response by Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1155/2014/315470,PMC4101967,25101271,CC BY,"Interferons (IFNs) are important components in innate immunity involved in the first line of defense to protect host against viral infection. Porcine reproductive and respiratory syndrome virus (PRRSV) leads to severe economic losses for swine industry since being first identified in early 1990s. PRRSV interplays with host IFN production and IFN-activated signaling, which may contribute to the delayed onset and low level of neutralizing antibodies, as well as weak cell-mediated immune response in infected pigs. PRRSV encodes several proteins that act as antagonists for the IFN signaling. In this review, we summarized the various strategies used by PRRSV to antagonize IFN production and thwart IFN-activated antiviral signaling, as well as the variable interference with IFN-mediated immune response by different PRRSV strains. Thorough understanding of the interaction between PRRSV and host innate immune response will facilitate elucidation of PRRSV pathogenesis and development of a better strategy to control PRRS.",2014 Jul 3,"['Wang, Rong', 'Zhang, Yan-Jin']",Biomed Res Int,,,True
fe2c4dd2b0a96acbdcd6566d94bf227c497995ef,PMC,"Fever Screening and Detection of Febrile Arrivals at an International Airport in Korea: Association among Self-reported Fever, Infrared Thermal Camera Scanning, and Tympanic Temperature",http://dx.doi.org/10.4178/epih/e2014004,PMC4101989,25045577,CC BY,"OBJECTIVES: The purpose of this research was to measure fever prevalence and the effectiveness of a fever screening procedure in detecting febrile arrivals at an international airport in Korea. METHODS: Data were retrieved from arrivals’ health declaration forms and questionnaires for febrile arrivals at an international airport collected by a national quarantine station during the year 2012. Self-reported health declaration forms were returned by 355,887 arrivals (61% of the total arrivals). Of these, 608 symptomatic arrivals (0.2%) including 6 febrile arrivals were analyzed. RESULTS: Fever prevalence at an international airport in Korea was 0.002%. Self-reported fever was significantly positively associated with tympanic temperature (p<0.001). The difference between the thermal camera temperature (36.83°C) and tympanic (or ear) temperature (38.14°C) was not statistically significant. CONCLUSIONS: The findings imply that a procedure for mass detection of fever such as self-reported questionnaires and thermal camera scanning may serve as an effective tool for detecting febrile arrivals at quarantine stations. Future research can benefit from looking at the sensitivity, specificity, positive predictive value, and negative predictive value of the entry screening system.",2014 May 30,"['Cho, Kyung Sook', 'Yoon, Jangho']",Epidemiol Health,,,True
dda497d889e111005663783d8ac3c1289e4a7f42,PMC,Quantifying the risk of respiratory infection in healthcare workers performing high-risk procedures,http://dx.doi.org/10.1017/S095026881300304X,PMC4102100,24308554,CC BY,"This study determined the risk of respiratory infection associated with high-risk procedures (HRPs) performed by healthcare workers (HCWs) in high-risk settings. We prospectively studied 481 hospital HCWs in China, documented risk factors for infection, including performing HRPs, measured new infections, and analysed whether HRPs predicted infection. Infection outcomes were clinical respiratory infection (CRI), laboratory-confirmed viral or bacterial infection, and an influenza infection. About 12% (56/481) of the study participants performed at least one HRP, the most common being airway suctioning (7·7%, 37/481). HCWs who performed a HRP were at significantly higher risk of developing CRI and laboratory-confirmed infection [adjusted relative risk 2·9, 95% confidence interval (CI) 1·42–5·87 and 2·9, 95% CI 1·37–6·22, respectively]. Performing a HRP resulted in a threefold increase in the risk of respiratory infections. This is the first time the risk has been prospectively quantified in HCWs, providing data to inform occupational health and safety policies.",2014 Sep 5,"['MACINTYRE, C. R.', 'SEALE, H.', 'YANG, P.', 'ZHANG, Y.', 'SHI, W.', 'ALMATROUDI, A.', 'MOA, A.', 'WANG, X.', 'LI, X.', 'PANG, X.', 'WANG, Q.']",Epidemiol Infect,,,True
015c335c8cb9e5eabb352e81c0f38bf6f781b202,PMC,Validation of three geolocation strategies for health-facility attendees for research and public health surveillance in a rural setting in western Kenya,http://dx.doi.org/10.1017/S0950268814000946,PMC4102101,24787145,CC BY,"Understanding the spatial distribution of disease is critical for effective disease control. Where formal address networks do not exist, tracking spatial patterns of clinical disease is difficult. Geolocation strategies were tested at rural health facilities in western Kenya. Methods included geocoding residence by head of compound, participatory mapping and recording the self-reported nearest landmark. Geocoding was able to locate 72·9% [95% confidence interval (CI) 67·7–77·6] of individuals to within 250 m of the true compound location. The participatory mapping exercise was able to correctly locate 82·0% of compounds (95% CI 78·9–84·8) to a 2 × 2·5 km area with a 500 m buffer. The self-reported nearest landmark was able to locate 78·1% (95% CI 73·8–82·1) of compounds to the correct catchment area. These strategies tested provide options for quickly obtaining spatial information on individuals presenting at health facilities.",2014 Sep 1,"['STRESMAN, G. H.', 'STEVENSON, J. C.', 'OWAGA, C.', 'MARUBE, E.', 'ANYANGO, C.', 'DRAKELEY, C.', 'BOUSEMA, T.', 'COX, J.']",Epidemiol Infect,,,True
dcf73eb12e0e246c75505f6723e6c10608963297,PMC,Synergistic Up-Regulation of CXCL10 by Virus and IFN γ in Human Airway Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0100978,PMC4102466,25033426,CC BY,"Airway epithelial cells are the first line of defense against viral infections and are instrumental in coordinating the inflammatory response. In this study, we demonstrate the synergistic stimulation of CXCL10 mRNA and protein, a key chemokine responsible for the early immune response to viral infection, following treatment of airway epithelial cells with IFN γ and influenza virus. The synergism also occurred when the cells were treated with IFN γ and a viral replication mimicker (dsRNA) both in vitro and in vivo. Despite the requirement of type I interferon (IFNAR) signaling in dsRNA-induced CXCL10, the synergism was independent of the IFNAR pathway since it wasn’t affected by the addition of a neutralizing IFNAR antibody or the complete lack of IFNAR expression. Furthermore, the same synergistic effect was also observed when a CXCL10 promoter reporter was examined. Although the responsive promoter region contains both ISRE and NFκB sites, western blot analysis indicated that the combined treatment of IFN γ and dsRNA significantly augmented NFκB but not STAT1 activation as compared to the single treatment. Therefore, we conclude that IFN γ and dsRNA act in concert to potentiate CXCL10 expression in airway epithelial cells via an NFκB-dependent but IFNAR-STAT independent pathway and it is at least partly regulated at the transcriptional level.",2014 Jul 17,"['Oslund, Karen L.', 'Zhou, Xu', 'Lee, Boram', 'Zhu, Lingxiang', 'Duong, Trang', 'Shih, Robert', 'Baumgarth, Nicole', 'Hung, Li-Yin', 'Wu, Reen', 'Chen, Yin']",PLoS One,,,True
4a17cedf8c94b518c91dfa6719832894b5dd0417,PMC,Excessive production and extreme editing of human metapneumovirus defective interfering RNA is associated with type I IFN induction,http://dx.doi.org/10.1099/vir.0.066100-0,PMC4103063,24760760,CC BY,"Type I IFN production is one of the hallmarks of host innate immune responses upon virus infection. Whilst most respiratory viruses carry IFN antagonists, reports on human metapneumovirus (HMPV) have been conflicting. Using deep sequencing, we have demonstrated that HMPV particles accumulate excessive amounts of defective interfering RNA (DIs) rapidly upon in vitro passage, and that these are associated with IFN induction. Importantly, the DIs were edited extensively; up to 70 % of the original A and T residues had mutated to G or C, respectively. Such high editing rates of viral RNA have not, to our knowledge, been reported before. Bioinformatics and PCR assays indicated that adenosine deaminase acting on RNA (ADAR) was the most likely editing enzyme. HMPV thus has an unusually high propensity to generate DIs, which are edited at an unprecedented high frequency. The conflicting published data on HMPV IFN induction and antagonism are probably explained by DIs in virus stocks. The interaction of HMPV DIs with the RNA-editing machinery and IFN responses warrants further investigation.",2014 Aug,"['van den Hoogen, Bernadette G.', 'van Boheemen, Sander', 'de Rijck, Jonneke', 'van Nieuwkoop, Stefan', 'Smith, Derek J.', 'Laksono, Brigitta', 'Gultyaev, Alexander', 'Osterhaus, Albert D. M. E.', 'Fouchier, Ron A. M.']",J Gen Virol,,,True
412e5e7d7abb90b1bbd1e91d1c89b937987e376e,PMC,Dynamically-Driven Enhancement of the Catalytic Machinery of the SARS 3C-Like Protease by the S284-T285-I286/A Mutations on the Extra Domain,http://dx.doi.org/10.1371/journal.pone.0101941,PMC4103764,25036652,CC BY,"Previously we revealed that the extra domain of SARS 3CLpro mediated the catalysis via different mechanisms. While the R298A mutation completely abolished the dimerization, thus resulting in the inactive catalytic machinery, N214A inactivated the enzyme by altering its dynamics without significantly perturbing its structure. Here we studied another mutant with S284-T285-I286 replaced by Ala (STI/A) with a 3.6-fold activity increase and slightly enhanced dimerization. We determined its crystal structure, which still adopts the dimeric structure almost identical to that of the wild-type (WT), except for slightly tighter packing between two extra-domains. We then conducted 100-ns molecular dynamics (MD) simulations for both STI/A and WT, the longest reported so far for 3CLpro. In the simulations, two STI/A extra domains become further tightly packed, leading to a significant volume reduction of the nano-channel formed by residues from both catalytic and extra domains. The enhanced packing appears to slightly increase the dynamic stability of the N-finger and the first helix residues, which subsequently triggers the redistribution of dynamics over residues directly contacting them. This ultimately enhances the dynamical stability of the residues constituting the catalytic dyad and substrate-binding pockets. Further correlation analysis reveals that a global network of the correlated motions exists in the protease, whose components include all residues identified so far to be critical for the dimerization and catalysis. Most strikingly, the N214A mutation globally decouples this network while the STI/A mutation alters the correlation pattern. Together with previous results, the present study establishes that besides the classic structural allostery, the dynamic allostery also operates in the SARS 3CLpro, which is surprisingly able to relay the perturbations on the extra domain onto the catalytic machinery to manifest opposite catalytic effects. Our results thus imply a promising avenue to design specific inhibitors for 3CL proteases by disrupting their dynamic correlation network.",2014 Jul 18,"['Lim, Liangzhong', 'Shi, Jiahai', 'Mu, Yuguang', 'Song, Jianxing']",PLoS One,,,True
dba0cdf3fbecdba11207ba0d7da322fc2a83b798,PMC,Building core capacities at the designated points of entry according to the International Health Regulations 2005: a review of the progress and prospects in Taiwan,http://dx.doi.org/10.3402/gha.v7.24516,PMC4104008,25037903,CC BY,"BACKGROUND: As designated points of entry (PoEs) play a critical role in preventing the transmission of international public health risks, huge efforts have been invested in Taiwan to improve the core capacities specified in the International Health Regulations 2005 (IHR 2005). This article reviews how Taiwan strengthened the core capacities at the Taoyuan International Airport (TIA) and the Port of Kaohsiung (PoK) by applying a new, practicable model. DESIGN: An IHR PoE program was initiated for implementing the IHR core capacities at designated PoEs. The main methods of this program were 1) identifying the designated PoEs according to the pre-determined criteria, 2) identifying the competent authority for each health measure, 3) building a close collaborative relationship between stakeholders from the central and PoE level, 4) designing three stages of systematic assessment using the assessment tool published by the World Health Organization (WHO), and 5) undertaking action plans targeting the gaps identified by the assessments. RESULTS: Results of the self-assessment, preliminary external assessment, and follow-up external assessment revealed a continuous progressive trend at the TIA (86, 91, and 100%, respectively), and at the PoK (77, 97, and 99.9%, respectively). The results of the follow-up external assessment indicated that both these designated PoEs already conformed to the IHR requirements. These achievements were highly associated with strong collaboration, continuous empowerment, efficient resource integration, and sustained commitments. CONCLUSIONS: Considering that many countries had requested for an extension on the deadline to fulfill the IHR 2005 core capacity requirements, Taiwan's experiences can be a source of learning for countries striving to fully implement these requirements. Further, in order to broaden the scope of public health protection into promoting global security, Taiwan will keep its commitments on multisectoral cooperation, human resource capacity building, and maintaining routine and emergency capacities.",2014 Jul 17,"['Chiu, Hsiao-Hsuan', 'Hsieh, Jui-Wei', 'Wu, Yi-Chun', 'Chou, Jih-Haw', 'Chang, Feng-Yee']",Glob Health Action,,,True
3c43e9e66c5b384ac03f0067bc8d16a9efdd5fb9,PMC,Choindroitinase ABC I-Mediated Enhancement of Oncolytic Virus Spread and Anti Tumor Efficacy: A Mathematical Model,http://dx.doi.org/10.1371/journal.pone.0102499,PMC4105445,25047810,CC BY,"Oncolytic viruses are genetically engineered viruses that are designed to kill cancer cells while doing minimal damage to normal healthy tissue. After being injected into a tumor, they infect cancer cells, multiply inside them, and when a cancer cell is killed they move on to spread and infect other cancer cells. Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove a major glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans without any deleterious effects in vivo. It has been shown that Chase-ABC treatment is able to promote the spread of the viruses, increasing the efficacy of the viral treatment. In this paper we develop a mathematical model to investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic viruses (OV). We show that the model's predictions agree with experimental results for a spherical glioma. We then use the model to test various treatment options in the heterogeneous microenvironment of the brain. The model predicts that separate injections of OV, one into the center of the tumor and another outside the tumor will result in better outcome than if the total injection is outside the tumor. In particular, the injection of the ECM-degrading enzyme (Chase-ABC) on the periphery of the main tumor core need to be administered in an optimal strategy in order to infect and eradicate the infiltrating glioma cells outside the tumor core in addition to proliferative cells in the bulk of tumor core. The model also predicts that the size of tumor satellites and distance between the primary tumor and multifocal/satellite lesions may be an important factor for the efficacy of the viral therapy with Chase treatment.",2014 Jul 21,"['Kim, Yangjin', 'Lee, Hyun Geun', 'Dmitrieva, Nina', 'Kim, Junseok', 'Kaur, Balveen', 'Friedman, Avner']",PLoS One,,,True
8dcc9848e421e45ac829203e4e6fe58e6ac130e5,PMC,Choindroitinase ABC I-Mediated Enhancement of Oncolytic Virus Spread and Anti Tumor Efficacy: A Mathematical Model,http://dx.doi.org/10.1371/journal.pone.0102499,PMC4105445,25047810,CC BY,"Oncolytic viruses are genetically engineered viruses that are designed to kill cancer cells while doing minimal damage to normal healthy tissue. After being injected into a tumor, they infect cancer cells, multiply inside them, and when a cancer cell is killed they move on to spread and infect other cancer cells. Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove a major glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans without any deleterious effects in vivo. It has been shown that Chase-ABC treatment is able to promote the spread of the viruses, increasing the efficacy of the viral treatment. In this paper we develop a mathematical model to investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic viruses (OV). We show that the model's predictions agree with experimental results for a spherical glioma. We then use the model to test various treatment options in the heterogeneous microenvironment of the brain. The model predicts that separate injections of OV, one into the center of the tumor and another outside the tumor will result in better outcome than if the total injection is outside the tumor. In particular, the injection of the ECM-degrading enzyme (Chase-ABC) on the periphery of the main tumor core need to be administered in an optimal strategy in order to infect and eradicate the infiltrating glioma cells outside the tumor core in addition to proliferative cells in the bulk of tumor core. The model also predicts that the size of tumor satellites and distance between the primary tumor and multifocal/satellite lesions may be an important factor for the efficacy of the viral therapy with Chase treatment.",2014 Jul 21,"['Kim, Yangjin', 'Lee, Hyun Geun', 'Dmitrieva, Nina', 'Kim, Junseok', 'Kaur, Balveen', 'Friedman, Avner']",PLoS One,,,True
9eff33e415aeff95305afd9a4914f15b1eafab84,PMC,"Viral etiology and seasonality of influenza-like illness in Gabon, March 2010 to June 2011",http://dx.doi.org/10.1186/1471-2334-14-373,PMC4107952,25000832,CC BY,"BACKGROUND: Surveillance of influenza-like illness (ILI) in Central Africa began only recently, and few data are therefore available on the circulation of influenza virus and other respiratory viruses. In Gabon, a Central African country, we established a surveillance network in four major towns in order to analyze cases of ILI among patients who visited health centers between March 2010 and June 2011, and to determine the viral etiology. METHODS: Nasal swabs were sent for analysis to the Centre International de Recherches Médicales de Franceville, where they were screened for 17 respiratory viruses in a multiplex real-time reverse transcription polymerase chain reaction for all pathogens according the following pairs: adenovirus/parainfluenza virus 4, respiratory syncytial virus/human metapneumovirus, parainfluenza virus 1/parainfluenza virus 2, pandemic influenza virus A/seasonal influenza virus A (H1N1, H3N2)/seasonal influenza virus B, human coronaviruses 229E/OC43, human coronaviruses NL63/HKU1, rhinovirus/human parechovirus, and enterovirus/parainfluenza virus 3. RESULTS: We analyzed a total of 1041 specimens, of which 639 (61%) were positive for at least one virus. Three-quarters of the patients were children under five years old. We therefore focused on this age group, in which 68.1% of patients were positive for at least one virus. The most common viruses were adenoviruses (17.5%), followed by parainfluenza viruses (PIVs) 1–4 (16.8%), enteroviruses (EV) (14.7%), respiratory syncytial virus (RSV) (13.5%), and influenza virus (11.9%). The prevalence of some viruses was subject to geographic and seasonal variations. One-third of positive samples contained more than one virus. CONCLUSIONS: Like most studies in the world, the virus PIVs, EV, RSV, Influenza virus, HRV were predominant among children under five years old in Gabon. An exception is made for adenoviruses which have a high prevalence in our study. However adenoviruses can be detected in asymptomatic persons. These finding gave a better knowledge of the circulation and the seasonality of the viruses involved in ILI in Gabon.",2014 Jul 7,"['Lekana-Douki, Sonia Etenna', 'Nkoghe, Dieudonné', 'Drosten, Christian', 'Ngoungou, Edgar Brice', 'Drexler, Jan Felix', 'Leroy, Eric M']",BMC Infect Dis,,,True
22371f1a9a91782adf48ffc5ad7d54d9a7a61b13,PMC,Q fever in the Netherlands: public perceptions and behavioral responses in three different epidemiological regions: a follow-up study,http://dx.doi.org/10.1186/1471-2458-14-263,PMC4108011,24645896,CC BY,"BACKGROUND: Over the past years, Q fever has become a major public health problem in the Netherlands, with a peak of 2,357 human cases in 2009. In the first instance, Q fever was mainly a local problem of one province with a high density of large dairy goat farms, but in 2009 an alarming increase of Q fever cases was observed in adjacent provinces. The aim of this study was to identify trends over time and regional differences in public perceptions and behaviors, as well as predictors of preventive behavior regarding Q fever. METHODS: One cross-sectional survey (2009) and two follow-up surveys (2010, 2012) were performed. Adults, aged ≥18 years, that participated in a representative internet panel were invited (survey 1, n = 1347; survey 2, n = 1249; survey 3, n = 1030). RESULTS: Overall, public perceptions and behaviors regarding Q fever were consistent with the trends over time in the numbers of new human Q fever cases in different epidemiological regions and the amount of media attention focused on Q fever in the Netherlands. However, there were remarkably low levels of perceived vulnerability and perceived anxiety, particularly in the region of highest incidence, where three-quarters of the total cases occurred in 2009. Predictors of preventive behavior were being female, older aged, having Q fever themselves or someone in their household, more knowledge, and higher levels of perceived severity, anxiety and (self-) efficacy. CONCLUSIONS: During future outbreaks of (zoonotic) infectious diseases, it will be important to instil a realistic sense of vulnerability by providing the public with accurate information on the risk of becoming infected. This should be given in addition to information about the severity of the disease, the efficacy of measures, and instructions for minimising infection risk with appropriate, feasible preventative measures. Furthermore, public information should be adapted to regional circumstances.",2014 Mar 20,"['Bults, Marloes', 'Beaujean, Desirée', 'Wijkmans, Clementine', 'Richardus, Jan Hendrik', 'Voeten, Hélène']",BMC Public Health,,,True
938354ea93017c47a439518c4d67178f63e70088,PMC,Recent advances in live cell imaging of hepatoma cells,http://dx.doi.org/10.1186/1471-2121-15-26,PMC4108253,25005127,CC BY,"Live cell imaging enables the study of dynamic processes of living cells in real time by use of suitable reporter proteins and the staining of specific cellular structures and/or organelles. With the availability of advanced optical devices and improved cell culture protocols it has become a rapidly growing research methodology. The success of this technique relies mainly on the selection of suitable reporter proteins, construction of recombinant plasmids possessing cell type specific promoters as well as reliable methods of gene transfer. This review aims to provide an overview of the recent developments in the field of marker proteins (bioluminescence and fluorescent) and methodologies (fluorescent resonance energy transfer, fluorescent recovery after photobleaching and proximity ligation assay) employed as to achieve an improved imaging of biological processes in hepatoma cells. Moreover, different expression systems of marker proteins and the modes of gene transfer are discussed with emphasis on the study of lipid droplet formation in hepatocytes as an example.",2014 Jul 8,"['Salipalli, Sandeep', 'Singh, Prafull Kumar', 'Borlak, Jürgen']",BMC Cell Biol,,,True
a795b134187db133ca06a515ab1bec787916af2d,PMC,"SELDI-TOF-MS Proteomic Profiling of Serum, Urine, and Amniotic Fluid in Neural Tube Defects",http://dx.doi.org/10.1371/journal.pone.0103276,PMC4108413,25054433,CC BY,"Neural tube defects (NTDs) are common birth defects, whose specific biomarkers are needed. The purpose of this pilot study is to determine whether protein profiling in NTD-mothers differ from normal controls using SELDI-TOF-MS. ProteinChip Biomarker System was used to evaluate 82 maternal serum samples, 78 urine samples and 76 amniotic fluid samples. The validity of classification tree was then challenged with a blind test set including another 20 NTD-mothers and 18 controls in serum samples, and another 19 NTD-mothers and 17 controls in urine samples, and another 20 NTD-mothers and 17 controls in amniotic fluid samples. Eight proteins detected in serum samples were up-regulated and four proteins were down-regulated in the NTD group. Four proteins detected in urine samples were up-regulated and one protein was down-regulated in the NTD group. Six proteins detected in amniotic fluid samples were up-regulated and one protein was down-regulated in the NTD group. The classification tree for serum samples separated NTDs from healthy individuals, achieving a sensitivity of 91% and a specificity of 97% in the training set, and achieving a sensitivity of 90% and a specificity of 97% and a positive predictive value of 95% in the test set. The classification tree for urine samples separated NTDs from controls, achieving a sensitivity of 95% and a specificity of 94% in the training set, and achieving a sensitivity of 89% and a specificity of 82% and a positive predictive value of 85% in the test set. The classification tree for amniotic fluid samples separated NTDs from controls, achieving a sensitivity of 93% and a specificity of 89% in the training set, and achieving a sensitivity of 90% and a specificity of 88% and a positive predictive value of 90% in the test set. These suggest that SELDI-TOF-MS is an additional method for NTDs pregnancies detection.",2014 Jul 23,"['Liu, Zhenjiang', 'Yuan, Zhengwei', 'Zhao, Qun']",PLoS One,,,True
3aa75376556fa96324ad4cacb0b862ad86b7a11e,PMC,A Novel MVA Vectored Chikungunya Virus Vaccine Elicits Protective Immunity in Mice,http://dx.doi.org/10.1371/journal.pntd.0002970,PMC4109897,25058320,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging arbovirus associated with febrile illness often accompanied by rash and arthralgia that may persist for several years. Outbreaks are associated with high morbidity and create a public health challenge for countries affected. Recent outbreaks have occurred in both Europe and the Americas, suggesting CHIKV may continue to spread. Despite the sustained threat of the virus, there is no approved vaccine or antiviral therapy against CHIKV. Therefore, it is critical to develop a vaccine that is both well tolerated and highly protective. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we describe the construction and characterization of a modified Vaccinia virus Ankara (MVA) virus expressing CHIKV E3 and E2 proteins (MVA-CHIK) that protected several mouse models from challenge with CHIKV. In particular, BALB/c mice were completely protected against viremia upon challenge with CHIKV after two doses of MVA-CHIK. Additionally, A129 mice (deficient in IFNα/β) were protected from viremia, footpad swelling, and mortality. While high anti-virus antibodies were elicited, low or undetectable levels of neutralizing antibodies were produced in both mouse models. However, passive transfer of MVA-CHIK immune serum to naïve mice did not protect against mortality, suggesting that antibodies may not be the main effectors of protection afforded by MVA-CHIK. Furthermore, depletion of CD4(+), but not CD8(+) T-cells from vaccinated mice resulted in 100% mortality, implicating the indispensable role of CD4(+) T-cells in the protection afforded by MVA-CHIK. CONCLUSIONS/SIGNIFICANCE: The results presented herein demonstrate the potential of MVA to effectively express CHIKV E3-E2 proteins and generate protective immune responses. Our findings challenge the assumption that only neutralizing antibodies are effective in providing protection against CHIKV, and provides a framework for the development of novel, more effective vaccine strategies to combat CHIKV.",2014 Jul 24,"['Weger-Lucarelli, James', 'Chu, Haiyan', 'Aliota, Matthew T.', 'Partidos, Charalambos D.', 'Osorio, Jorge E.']",PLoS Negl Trop Dis,,,True
f8f2a61fb217ad9fb00b93b7ec2bbb016bcbb881,PMC,Using Informatics and the Electronic Medical Record to Describe Antimicrobial Use in the Clinical Management of Diarrhea Cases at 12 Companion Animal Practices,http://dx.doi.org/10.1371/journal.pone.0103190,PMC4109994,25057893,CC BY,"Antimicrobial drugs may be used to treat diarrheal illness in companion animals. It is important to monitor antimicrobial use to better understand trends and patterns in antimicrobial resistance. There is no monitoring of antimicrobial use in companion animals in Canada. To explore how the use of electronic medical records could contribute to the ongoing, systematic collection of antimicrobial use data in companion animals, anonymized electronic medical records were extracted from 12 participating companion animal practices and warehoused at the University of Calgary. We used the pre-diagnostic, clinical features of diarrhea as the case definition in this study. Using text-mining technologies, cases of diarrhea were described by each of the following variables: diagnostic laboratory tests performed, the etiological diagnosis and antimicrobial therapies. The ability of the text miner to accurately describe the cases for each of the variables was evaluated. It could not reliably classify cases in terms of diagnostic tests or etiological diagnosis; a manual review of a random sample of 500 diarrhea cases determined that 88/500 (17.6%) of the target cases underwent diagnostic testing of which 36/88 (40.9%) had an etiological diagnosis. Text mining, compared to a human reviewer, could accurately identify cases that had been treated with antimicrobials with high sensitivity (92%, 95% confidence interval, 88.1%–95.4%) and specificity (85%, 95% confidence interval, 80.2%–89.1%). Overall, 7400/15,928 (46.5%) of pets presenting with diarrhea were treated with antimicrobials. Some temporal trends and patterns of the antimicrobial use are described. The results from this study suggest that informatics and the electronic medical records could be useful for monitoring trends in antimicrobial use.",2014 Jul 24,"['Anholt, R. Michele', 'Berezowski, John', 'Ribble, Carl S.', 'Russell, Margaret L.', 'Stephen, Craig']",PLoS One,,,True
a35a9ab63e50b5eed8710a67b89d6c31d53cd191,PMC,Risk factors and epidemiological characteristics of new neonatal porcine diarrhoea syndrome in four Danish herds,http://dx.doi.org/10.1186/1746-6148-10-151,PMC4110237,25012922,CC BY,"BACKGROUND: The epidemiology of New Neonatal Porcine Diarrhoea Syndrome (NNPDS) was studied in four selected herds. A total of 941 new born piglets in 86 litters were evaluated for five consecutive days. NNPDS is a newly emerged syndrome, characterized by diarrhoea within the first week of life, which is un-responsive to antibiotics and not associated with known pathogens. The aetiology behind the syndrome is unknown, and specific risk factors predisposing piglets to develop NNPDS also remain to be determined. The study evaluated sow and piglet-level risk factors for developing NNPDS and described the epidemiologic characteristics within four herds previously diagnosed with the syndrome. NNPDS was defined as diarrhoea at any time-point during the second to fifth day of life. RESULTS: NNPDS was observed in a total of 60% (range: 39%-89%) of first parity piglets and 36% (range: 19-65%) of piglets born by mature sows. In total of 26% of piglets had liquid faeces on the day of birth. Approximately half of these piglets developed NNPDS. In the majority of cases (50-70% of cases within herds) symptoms started on the second or third day of life. Piglets in Herd 1 had12.8 times higher probability of developing NNPDS than piglets in Herd 4. First parity piglets had a 4.1 higher probability of developing NNPDS than piglets born by mature sows. Birth weight and faecal consistency on the day of birth were minor risk factors, each significant within one herd. CONCLUSIONS: The most important factors associated with NNPDS were herd of origin and sow-parity. The reason for one of the herds experiencing a considerably more severe outbreak than the others was not explained by factors addressed in this study. The epidemiological pattern of diarrhoea varied a lot between herds; however, in all herds first parity piglets seemed predisposed. This association may be explained by an infectious background of the syndrome, but further studies are needed to explain this association.",2014 Jul 10,"['Kongsted, Hanne', 'Toft, Nils', 'Nielsen, Jens Peter']",BMC Vet Res,,,True
42d750019224d03261c70185a1bae3afe5be8c3a,PMC,Draft Genome Sequence of the Bordetella bronchiseptica Swine Isolate KM22,http://dx.doi.org/10.1128/genomeA.00670-14,PMC4110755,25013141,CC BY,Bordetella bronchiseptica swine isolate KM22 has been used in experimental infections of swine as a model of clinical B. bronchiseptica infections within swine herds and to study host-to-host transmission. Here we report the draft genome sequence of KM22.,2014 Jul 10,"['Nicholson, Tracy L.', 'Shore, Sarah M.', 'Bayles, Darrell O.', 'Register, Karen B.', 'Kingsley, Robert A.']",Genome Announc,,,True
284a7df2b370e893122a58ce3af9a9d2daaab704,PMC,A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection,http://dx.doi.org/10.7554/eLife.02910,PMC4112549,24966209,CC0,"Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-κB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells and for pathogenesis in mice. Interestingly, A51R colocalizes with, and stabilizes, host microtubules and also associates with ubiquitin. We show that A51R promotes viral protein stability, possibly by preventing ubiquitin-dependent targeting of viral proteins for destruction. Importantly, our studies reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems. DOI: http://dx.doi.org/10.7554/eLife.02910.001",2014 Jun 25,"['Gammon, Don B', 'Duraffour, Sophie', 'Rozelle, Daniel K', 'Hehnly, Heidi', 'Sharma, Rita', 'Sparks, Michael E', 'West, Cara C', 'Chen, Ying', 'Moresco, James J', 'Andrei, Graciela', 'Connor, John H', 'Conte, Darryl', 'Gundersen-Rindal, Dawn E', 'Marshall, William L', 'Yates, John R', 'Silverman, Neal', 'Mello, Craig C']",eLife,,,True
c7d60067e11331d3c5e1f9b1d79e70caacb13f25,PMC,Kawasaki disease patients homozygous for the rs12252-C variant of interferon-induced transmembrane protein-3 are significantly more likely to develop coronary artery lesions,http://dx.doi.org/10.1002/mgg3.79,PMC4113277,25077179,CC BY,,2014 Jul 14,"['Bowles, Neil E', 'Arrington, Cammon B', 'Hirono, Keiichi', 'Nakamura, Tsuneyuki', 'Ngo, Long', 'Wee, Yin Shen', 'Ichida, Fukiko', 'Weis, John H']",Mol Genet Genomic Med,,,True
7db22f7f81977109d493a0edf8ed75562648e839,PMC,Recombinant Scorpine Produced Using SUMO Fusion Partner in Escherichia coli Has the Activities against Clinically Isolated Bacteria and Inhibits the Plasmodium falciparum Parasitemia In Vitro,http://dx.doi.org/10.1371/journal.pone.0103456,PMC4113386,25068263,CC BY,"Scorpine, a small cationic peptide from the venom of Pandinus imperator, which has been shown to have anti-bacterial and anti-plasmodial activities, has potential important applications in the pharmaceutical industries. However, the isolation of scorpine from natural sources is inefficient and time-consuming. Here, we first report the expression and purification of recombinant scorpine in Escherichia coli, using small ubiquitin-related modifier (SUMO) fusion partner. The fusion protein was expressed in soluble form in E. coli, and expression was verified by SDS-PAGE and western blotting analysis. The fusion protein was purified to 90% purity by nickel–nitrilotriacetic acid (Ni(2+)–NTA) resin chromatography. After the SUMO-scorpine fusion protein was cleaved by the SUMO protease, the cleaved sample was reapplied to a Ni(2+)–NTA column. Tricine/SDS-PAGE gel results indicated that Scorpine had been purified successfully to more than 95% purity. The recombinantly expressed Scorpine showed anti-bacterial activity against two standard bacteria including Staphylococcus aureus ATCC 29213 and Acinetobacter baumannii ATCC 19606, and clinically isolated bacteria including S. aureus S, S. aureus R, A. baumannii S, and A. baumannii R. It also produced 100% reduction in Plasmodium falciparum parasitemia in vitro. Thus, the expression strategy presented in this study allowed convenient high yield and easy purification of recombinant Scorpine for pharmaceutical applications in the future.",2014 Jul 28,"['Zhang, Chao', 'He, Xinlong', 'Gu, Yaping', 'Zhou, Huayun', 'Cao, Jun', 'Gao, Qi']",PLoS One,,,True
8086b478a036f07fc6a809c63dc7d52acb659fe1,PMC,RNA Virus Reverse Genetics and Vaccine Design,http://dx.doi.org/10.3390/v6072531,PMC4113782,24967693,CC BY,"RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines.",2014 Jun 25,"['Stobart, Christopher C.', 'Moore, Martin L.']",Viruses,,,True
6223b84467e6bdc875ce49a403acf34055e4d141,PMC,Modified Vaccinia Virus Ankara (MVA) as Production Platform for Vaccines against Influenza and Other Viral Respiratory Diseases,http://dx.doi.org/10.3390/v6072735,PMC4113791,25036462,CC BY,"Respiratory viruses infections caused by influenza viruses, human parainfluenza virus (hPIV), respiratory syncytial virus (RSV) and coronaviruses are an eminent threat for public health. Currently, there are no licensed vaccines available for hPIV, RSV and coronaviruses, and the available seasonal influenza vaccines have considerable limitations. With regard to pandemic preparedness, it is important that procedures are in place to respond rapidly and produce tailor made vaccines against these respiratory viruses on short notice. Moreover, especially for influenza there is great need for the development of a universal vaccine that induces broad protective immunity against influenza viruses of various subtypes. Modified Vaccinia Virus Ankara (MVA) is a replication-deficient viral vector that holds great promise as a vaccine platform. MVA can encode one or more foreign antigens and thus functions as a multivalent vaccine. The vector can be used at biosafety level 1, has intrinsic adjuvant capacities and induces humoral and cellular immune responses. However, there are some practical and regulatory issues that need to be addressed in order to develop MVA-based vaccines on short notice at the verge of a pandemic. In this review, we discuss promising novel influenza virus vaccine targets and the use of MVA for vaccine development against various respiratory viruses.",2014 Jul 17,"['Altenburg, Arwen F.', 'Kreijtz, Joost H. C. M.', 'de Vries, Rory D.', 'Song, Fei', 'Fux, Robert', 'Rimmelzwaan, Guus F.', 'Sutter, Gerd', 'Volz, Asisa']",Viruses,,,True
b8aeb68acc940bb4f4d68bb6e7bb89da81c5d12f,PMC,Membranous Replication Factories Induced by Plus-Strand RNA Viruses,http://dx.doi.org/10.3390/v6072826,PMC4113795,25054883,CC BY,"In this review, we summarize the current knowledge about the membranous replication factories of members of plus-strand (+) RNA viruses. We discuss primarily the architecture of these complex membrane rearrangements, because this topic emerged in the last few years as electron tomography has become more widely available. A general denominator is that two “morphotypes” of membrane alterations can be found that are exemplified by flaviviruses and hepaciviruses: membrane invaginations towards the lumen of the endoplasmatic reticulum (ER) and double membrane vesicles, representing extrusions also originating from the ER, respectively. We hypothesize that either morphotype might reflect common pathways and principles that are used by these viruses to form their membranous replication compartments.",2014 Jul 22,"['Romero-Brey, Inés', 'Bartenschlager, Ralf']",Viruses,,,True
bd392572caeafc342bc6b6c54ad637bb8c2dfe4b,PMC,Usage of Social Media and Smartphone Application in Assessment of Physical and Psychological Well-Being of Individuals in Times of a Major Air Pollution Crisis,http://dx.doi.org/10.2196/mhealth.2827,PMC4114481,25098255,CC BY,"BACKGROUND: Crisis situations bring about many challenges to researchers, public institutions, and governments in collecting data and conducting research in affected individuals. Recent developments in Web-based and smartphone technologies have offered government and nongovernment organizations a new system to disseminate and acquire information. However, research into this area is still lacking. The current study focuses largely on how new social networking websites and, in particular, smartphone technologies could have helped in the acquisition of crucial research data from the general population during the recent 2013 Southeast Asian Haze. This crisis lasted only for 1 week, and is unlike other crisis where there are large-scale consequential after-effects. OBJECTIVE: To determine whether respondents will make use of Internet, social media, and smartphone technologies to provide feedback regarding their physical and psychological wellbeing during a crisis, and if so, will these new mechanisms be as effective as conventional, technological, Internet-based website technologies. METHODS: A Web-based database and a smartphone application were developed. Participants were recruited by snowball sampling. The participants were recruited either via a self-sponsored Facebook post featuring a direct link to the questionnaire on physical and psychological wellbeing and also a smartphone Web-based application; or via dissemination of the questionnaire link by emails, directed to the same group of participants. Information pertaining to physical and psychological wellbeing was collated. RESULTS: A total of 298 respondents took part in the survey. Most of them were between the ages of 20 to 29 years and had a university education. More individuals preferred the option of accessing and providing feedback to a survey on physical and psychological wellbeing via direct access to a Web-based questionnaire. Statistical analysis showed that demographic variables like age, gender, and educational levels did not influence the mechanism of access. In addition, the participants reported a mean number of 4.03 physical symptoms (SD 2.6). The total Impact of Event Scale–Revised (IES-R) score was 18.47 (SD 11.69), which indicated that the study population did experience psychological stress but not post-traumatic stress disorder. The perceived dangerous Pollutant Standards Index (PSI) level and the number of physical symptoms were associated with higher IES-R Score (P<.05). CONCLUSIONS: This is one of the first few studies demonstrating the use of Internet in data collection during an air-pollution crisis. Our results demonstrated that the newer technological modalities have the potential to acquire data, similar to that of conventional technologies. Demographic variables did not influence the mechanism of usage. In addition, our findings also suggested that there are acute physical and psychological impacts on the population from an air-pollution crisis.",2014 Mar 25,"['Zhang, Melvyn WB', 'Ho, Cyrus SH', 'Fang, Pan', 'Lu, Yanxia', 'Ho, Roger CM']",JMIR Mhealth Uhealth,,,False
6424a93c7b3cafd9bbe5c14bfc35940c81f9333e,PMC,Usage of Social Media and Smartphone Application in Assessment of Physical and Psychological Well-Being of Individuals in Times of a Major Air Pollution Crisis,http://dx.doi.org/10.2196/mhealth.2827,PMC4114481,25098255,CC BY,"BACKGROUND: Crisis situations bring about many challenges to researchers, public institutions, and governments in collecting data and conducting research in affected individuals. Recent developments in Web-based and smartphone technologies have offered government and nongovernment organizations a new system to disseminate and acquire information. However, research into this area is still lacking. The current study focuses largely on how new social networking websites and, in particular, smartphone technologies could have helped in the acquisition of crucial research data from the general population during the recent 2013 Southeast Asian Haze. This crisis lasted only for 1 week, and is unlike other crisis where there are large-scale consequential after-effects. OBJECTIVE: To determine whether respondents will make use of Internet, social media, and smartphone technologies to provide feedback regarding their physical and psychological wellbeing during a crisis, and if so, will these new mechanisms be as effective as conventional, technological, Internet-based website technologies. METHODS: A Web-based database and a smartphone application were developed. Participants were recruited by snowball sampling. The participants were recruited either via a self-sponsored Facebook post featuring a direct link to the questionnaire on physical and psychological wellbeing and also a smartphone Web-based application; or via dissemination of the questionnaire link by emails, directed to the same group of participants. Information pertaining to physical and psychological wellbeing was collated. RESULTS: A total of 298 respondents took part in the survey. Most of them were between the ages of 20 to 29 years and had a university education. More individuals preferred the option of accessing and providing feedback to a survey on physical and psychological wellbeing via direct access to a Web-based questionnaire. Statistical analysis showed that demographic variables like age, gender, and educational levels did not influence the mechanism of access. In addition, the participants reported a mean number of 4.03 physical symptoms (SD 2.6). The total Impact of Event Scale–Revised (IES-R) score was 18.47 (SD 11.69), which indicated that the study population did experience psychological stress but not post-traumatic stress disorder. The perceived dangerous Pollutant Standards Index (PSI) level and the number of physical symptoms were associated with higher IES-R Score (P<.05). CONCLUSIONS: This is one of the first few studies demonstrating the use of Internet in data collection during an air-pollution crisis. Our results demonstrated that the newer technological modalities have the potential to acquire data, similar to that of conventional technologies. Demographic variables did not influence the mechanism of usage. In addition, our findings also suggested that there are acute physical and psychological impacts on the population from an air-pollution crisis.",2014 Mar 25,"['Zhang, Melvyn WB', 'Ho, Cyrus SH', 'Fang, Pan', 'Lu, Yanxia', 'Ho, Roger CM']",JMIR Mhealth Uhealth,,,False
a445e4cc0146046d191344e3b61cd8dd4f33eb83,PMC,Human Coronaviruses Associated with Upper Respiratory Tract Infections in Three Rural Areas of Ghana,http://dx.doi.org/10.1371/journal.pone.0099782,PMC4117488,25080241,CC BY,"BACKGROUND: Acute respiratory tract infections (ARI) are the leading cause of morbidity and mortality in developing countries, especially in Africa. This study sought to determine whether human coronaviruses (HCoVs) are associated with upper respiratory tract infections among older children and adults in Ghana. METHODS: We conducted a case control study among older children and adults in three rural areas of Ghana using asymptomatic subjects as controls. Nasal/Nasopharyngeal swabs were tested for Middle East respiratory syndrome coronavirus (MERS-CoV), HCoV-22E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 using Reverse Transcriptase Real-Time Polymerase Chain Reaction. RESULTS: Out of 1,213 subjects recruited, 150 (12.4%) were positive for one or more viruses. Of these, single virus detections occurred in 146 subjects (12.0%) and multiple detections occurred in 4 (0.3%). Compared with control subjects, infections with HCoV-229E (OR = 5.15, 95%CI = 2.24–11.78), HCoV-OC43 (OR = 6.16, 95%CI = 1.77–21.65) and combine HCoVs (OR = 2.36, 95%CI = 1.5 = 3.72) were associated with upper respiratory tract infections. HCoVs were found to be seasonally dependent with significant detections in the harmattan season (mainly HCoV-229E) and wet season (mainly HCoV-NL63). A comparison of the obtained sequences resulted in no differences to sequences already published in GenBank. CONCLUSION: HCoVs could play significant role in causing upper respiratory tract infections among adults and older children in rural areas of Ghana.",2014 Jul 31,"['Owusu, Michael', 'Annan, Augustina', 'Corman, Victor Max', 'Larbi, Richard', 'Anti, Priscilla', 'Drexler, Jan Felix', 'Agbenyega, Olivia', 'Adu-Sarkodie, Yaw', 'Drosten, Christian']",PLoS One,,,True
c83a4991d36a6086da50b13968955329c5f07a6c,PMC,Inflammatory response in mixed viral-bacterial community-acquired pneumonia,http://dx.doi.org/10.1186/1471-2466-14-123,PMC4118651,25073709,CC BY,"BACKGROUND: The role of mixed pneumonia (virus + bacteria) in community-acquired pneumonia (CAP) has been described in recent years. However, it is not known whether the systemic inflammatory profile is different compared to monomicrobial CAP. We wanted to investigate this profile of mixed viral-bacterial infection and to compare it to monomicrobial bacterial or viral CAP. METHODS: We measured baseline serum procalcitonin (PCT), C reactive protein (CRP), and white blood cell (WBC) count in 171 patients with CAP with definite etiology admitted to a tertiary hospital: 59 (34.5%) bacterial, 66 (39.%) viral and 46 (27%) mixed (viral-bacterial). RESULTS: Serum PCT levels were higher in mixed and bacterial CAP compared to viral CAP. CRP levels were higher in mixed CAP compared to the other groups. CRP was independently associated with mixed CAP. CRP levels below 26 mg/dL were indicative of an etiology other than mixed in 83% of cases, but the positive predictive value was 45%. PCT levels over 2.10 ng/mL had a positive predictive value for bacterial-involved CAP versus viral CAP of 78%, but the negative predictive value was 48%. CONCLUSIONS: Mixed CAP has a different inflammatory pattern compared to bacterial or viral CAP. High CRP levels may be useful for clinicians to suspect mixed CAP.",2014 Jul 29,"['Bello, Salvador', 'Mincholé, Elisa', 'Fandos, Sergio', 'Lasierra, Ana B', 'Ruiz, María A', 'Simon, Ana L', 'Panadero, Carolina', 'Lapresta, Carlos', 'Menendez, Rosario', 'Torres, Antoni']",BMC Pulm Med,,,True
ed02cdbaaf52f191ad3bebb5a3bc117524718c8e,PMC,Establishment and Clinical Applications of a Portable System for Capturing Influenza Viruses Released through Coughing,http://dx.doi.org/10.1371/journal.pone.0103560,PMC4118893,25083787,CC BY,"Coughing plays an important role in influenza transmission; however, there is insufficient information regarding the viral load in cough because of the lack of convenient and reliable collection methods. We developed a portable airborne particle-collection system to measure the viral load; it is equipped with an air sampler to draw air and pass it through a gelatin membrane filter connected to a cone-shaped, megaphone-like device to guide the cough airflow to the membrane. The membrane was dissolved in a medium, and the viral load was measured using quantitative real-time reverse transcriptase-polymerase chain reaction and a plaque assay. The approximate viral recovery rate of this system was 10% in simulation experiments to collect and quantify the viral particles aerosolized by a nebulizer. Using this system, cough samples were collected from 56 influenza A patients. The total viral detection rate was 41% (23/56), and the viral loads varied significantly (from <10, less than the detection limit, to 2240 viral gene copies/cough). Viable viruses were detected from 3 samples with ≤18 plaque forming units per cough sample. The virus detection rates were similar among different groups of patients infected with different viral subtypes and during different influenza seasons. Among patients who did not receive antiviral treatment, viruses were detected in one of six cases in the vaccinated group and four of six cases in the unvaccinated group. We found cases with high viral titers in throat swabs or oral secretions but very low or undetectable in coughs and vice versa suggesting other possible anatomical sites where the viruses might be mixed into the cough. Our system is easy to operate, appropriate for bedside use, and is useful for comparing the viral load in cough samples from influenza patients under various conditions and settings. However, further large-scale studies are warranted to validate our results.",2014 Aug 1,"['Hatagishi, Etsuko', 'Okamoto, Michiko', 'Ohmiya, Suguru', 'Yano, Hisakazu', 'Hori, Toru', 'Saito, Wakana', 'Miki, Hiroshi', 'Suzuki, Yasushi', 'Saito, Reiko', 'Yamamoto, Taro', 'Shoji, Makoto', 'Morisaki, Yoshihisa', 'Sakata, Soichiro', 'Nishimura, Hidekazu']",PLoS One,,,True
18fb0cf6fba22d9478d4f5774f37f6b6bf09f3b0,PMC,Simultaneous Detection and Differentiation of Highly Virulent and Classical Chinese-Type Isolation of PRRSV by Real-Time RT-PCR,http://dx.doi.org/10.1155/2014/809656,PMC4119655,25114934,CC BY,"Porcine reproductive and respiratory syndrome (PRRS) is a leading disease in pig industry worldwide and can result in serious economic losses each year. The PRRS epidemic situation in China has been very complicated since the unprecedented large-scale highly pathogenic PRRS (HP-PRRS) outbreaks in 2006. And now the HP-PRRS virus (HP-PRRSV) and classical North American type PRRSV strains have coexisted in China. Rapid differential detection of the two strains of PRRSV is very important for effective PRRS control. The real-time RT-PCR for simultaneous detection and differentiation of HP-PRRSV and PRRSV by using both SYBR Green and TaqMan probes was developed and validated. Both assays can be used for rapid detection and strain-specific identification of HP-PRRSV and PRRSV. However, the TaqMan probe method had the highest detection rate whereas the conventional RT-PCR was the lowest. The real-time RT-PCR developed based on SYBR Green and TaqMan probe could be used for simultaneous detection and differentiation of HP-PRRSV and PRRSV in China, which will benefit much the PRRS control and research.",2014 Jun 12,"['Xiao, Shuqi', 'Chen, Yaosheng', 'Wang, Liangliang', 'Gao, Jintao', 'Mo, Delin', 'He, Zuyong', 'Liu, Xiaohong']",J Immunol Res,,,True
37142e322bc30493a97e2aff05533919897e39ef,PMC,"Using exercises to improve public health preparedness in Asia, the Middle East and Africa",http://dx.doi.org/10.1186/1756-0500-7-474,PMC4120002,25063987,CC BY,"BACKGROUND: Exercises are increasingly common tools used by the health sector and other sectors to evaluate their preparedness to respond to public health threats. Exercises provide an opportunity for multiple sectors to practice, test and evaluate their response to all types of public health emergencies. The information from these exercises can be used to refine and improve preparedness plans. There is a growing body of literature about the use of exercises among local, state and federal public health agencies in the United States. There is much less information about the use of exercises among public health agencies in other countries and the use of exercises that involve multiple countries. RESULTS: We developed and conducted 12 exercises (four sub-national, five national, three sub-regional) from August 2006 through December 2008. These 12 exercises included 558 participants (average 47) and 137 observers (average 11) from 14 countries. Participants consistently rated the overall quality of the exercises as very good or excellent. They rated the exercises lowest on their ability to identifying key gaps in performance. The vast majority of participants noted that they would use the information they gained at the exercise to improve their organization’s preparedness to respond to an influenza pandemic. Participants felt the exercises were particularly good at raising awareness and understanding about public health threats, assisting in evaluating plans and identifying priorities for improvement, and building relationships that strengthen preparedness and response across sectors and across countries. Participants left the exercises with specific ideas about the most important actions that they should engage in after the exercise such as improved planning coordination across sectors and countries and better training of health workers and response personnel. CONCLUSIONS: These experiences suggest that exercises can be a valuable, low-burden tool to improve emergency preparedness and response in countries around the world. They also demonstrate that countries can work together to develop and conduct successful exercises designed to improve regional preparedness to public health threats. The development of standardized evaluation methods for exercises may be an additional tool to help focus the actions to be taken as a result of the exercise and to improve future exercises. Exercises show great promise as tools to improve public health preparedness across sectors and countries.",2014 Jul 27,"['Dausey, David J', 'Moore, Melinda']",BMC Res Notes,,,True
969c9813397caecc9597daa9679e1bff3bc42635,PMC,Switch from Cap- to Factorless IRES-Dependent 0 and +1 Frame Translation during Cellular Stress and Dicistrovirus Infection,http://dx.doi.org/10.1371/journal.pone.0103601,PMC4121135,25089704,CC BY,"Internal ribosome entry sites (IRES) are utilized by a subset of cellular and viral mRNAs to initiate translation during cellular stress and virus infection when canonical cap-dependent translation is compromised. The intergenic region (IGR) IRES of the Dicistroviridae uses a streamlined mechanism in which it can directly recruit the ribosome in the absence of initiation factors and initiates translation using a non-AUG codon. A subset of IGR IRESs including that from the honey bee viruses can also direct translation of an overlapping +1 frame gene. In this study, we systematically examined cellular conditions that lead to IGR IRES-mediated 0 and +1 frame translation in Drosophila S2 cells. Towards this, a novel bicistronic reporter that exploits the 2A “stop-go” peptide was developed to allow the detection of IRES-mediated translation in vivo. Both 0 and +1 frame translation by the IGR IRES are stimulated under a number of cellular stresses and in S2 cells infected by cricket paralysis virus, demonstrating a switch from cap-dependent to IRES-dependent translation. The regulation of the IGR IRES mechanism ensures that both 0 frame viral structural proteins and +1 frame ORFx protein are optimally expressed during virus infection.",2014 Aug 4,"['Wang, Qing S.', 'Jan, Eric']",PLoS One,,,True
79be2bad7d0442947cec07b060a5b21f8eff7c72,PMC,Involvement of the ERK pathway in the protective effects of glycyrrhizic acid against the MPP(+)-induced apoptosis of dopaminergic neuronal cells,http://dx.doi.org/10.3892/ijmm.2014.1830,PMC4121344,24993693,CC BY,"Glycyrrhizic acid (GA), a major compound separated from Radix Glycyrrhizae, has been shwon to exert various biochemical effects, including neuroprotective effects. In the present study, we investigated the protective effects of GA against 1-methyl-4-phenylpyridinium (MPP(+))-induced damage to differentiated PC12 (DPC12) cells. Compared with the MPP(+)-treated cells, GA markedly improved cell viability, restored mitochondrial dysfunction, suppressed the overexpression of cleaved poly(ADP-ribose) polymerase (PARP), and suppressed the overproduction of lactate dehydrogenase (LDH) and intracellular Ca(2+) overload. The protective effects of GA on cell survival were further confirmed in primary cortical neurons. GA markedly increased the expression of phosphorylated extracellular signal-regulated kinase (p-ERK), as well as its migration from the cytoplasm to nucleus. PD98059, an inhibitor of ERK, blocked GA-enhanced ERK activation and reduced cell viability. However, pre-treatment with GA had no effects on the expression of phosphorylated AKT (p-AKT) and total AKT (t-AKT). These results indicate that the GA-mediated neuroprotective effects are associated with its modulation of multiple anti-apoptotic and pro-apoptotic factors, particularly the ERK signaling pathway. This study provides evidence supporting the use of GA as a potential therapeutic agent for the treatment of neurodegenerative diseases and neuronal injury.",2014 Sep 2,"['TENG, LESHENG', 'KOU, CHUNJIA', 'LU, CHENGYU', 'XU, JIAMING', 'XIE, JING', 'LU, JIAHUI', 'LIU, YAN', 'WANG, ZHENZUO', 'WANG, DI']",Int J Mol Med,,,True
40b7ed2533e026bb5323b85f9d81379ae0f17821,PMC,"ER stress, autophagy, and RNA viruses",http://dx.doi.org/10.3389/fmicb.2014.00388,PMC4122171,25140166,CC BY,"Endoplasmic reticulum (ER) stress is a general term for representing the pathway by which various stimuli affect ER functions. ER stress induces the evolutionarily conserved signaling pathways, called the unfolded protein response (UPR), which compromises the stimulus and then determines whether the cell survives or dies. In recent years, ongoing research has suggested that these pathways may be linked to the autophagic response, which plays a key role in the cell's response to various stressors. Autophagy performs a self-digestion function, and its activation protects cells against certain pathogens. However, the link between the UPR and autophagy may be more complicated. These two systems may act dependently, or the induction of one system may interfere with the other. Experimental studies have found that different viruses modulate these mechanisms to allow them to escape the host immune response or, worse, to exploit the host's defense to their advantage; thus, this topic is a critical area in antiviral research. In this review, we summarize the current knowledge about how RNA viruses, including influenza virus, poliovirus, coxsackievirus, enterovirus 71, Japanese encephalitis virus, hepatitis C virus, and dengue virus, regulate these processes. We also discuss recent discoveries and how these will produce novel strategies for antiviral treatment.",2014 Aug 5,"['Jheng, Jia-Rong', 'Ho, Jin-Yuan', 'Horng, Jim-Tong']",Front Microbiol,,,True
f48a26496eec9f955c65e9d89305c4bc5df2718a,PMC,"IRF7 in the Australian Black Flying Fox, Pteropus alecto: Evidence for a Unique Expression Pattern and Functional Conservation",http://dx.doi.org/10.1371/journal.pone.0103875,PMC4123912,25100081,CC BY,"As the only flying mammal, bats harbor a number of emerging and re-emerging viruses, many of which cause severe diseases in humans and other mammals yet result in no clinical symptoms in bats. As the master regulator of the interferon (IFN)-dependent immune response, IFN regulatory factor 7 (IRF7) plays a central role in innate antiviral immunity. To explore the role of bat IRF7 in the regulation of the IFN response, we performed sequence and functional analysis of IRF7 from the pteropid bat, Pteropus alecto. Our results demonstrate that bat IRF7 retains the ability to bind to MyD88 and activate the IFN response despite unique changes in the MyD88 binding domain. We also demonstrate that bat IRF7 has a unique expression pattern across both immune and non-immune related tissues and is inducible by double-strand RNA. The broad tissue distribution of IRF7 may provide bats with an enhanced ability to rapidly activate the IFN response in a wider range of tissues compared to other mammals. The importance of IRF7 in antiviral activity against the bat reovirus, Pulau virus was confirmed by siRNA knockdown of IRF7 in bat cells resulting in enhanced viral replication. Our results highlight the importance of IRF7 in innate antiviral immunity in bats.",2014 Aug 6,"['Zhou, Peng', 'Cowled, Chris', 'Mansell, Ashley', 'Monaghan, Paul', 'Green, Diane', 'Wu, Lijun', 'Shi, Zhengli', 'Wang, Lin-Fa', 'Baker, Michelle L.']",PLoS One,,,True
f6f669e9a8834d3c4c054d99f3ffd548a40a1059,PMC,ELM: enhanced lowest common ancestor based method for detecting a pathogenic virus from a large sequence dataset,http://dx.doi.org/10.1186/1471-2105-15-254,PMC4124145,25069839,CC BY,"BACKGROUND: Emerging viral diseases, most of which are caused by the transmission of viruses from animals to humans, pose a threat to public health. Discovering pathogenic viruses through surveillance is the key to preparedness for this potential threat. Next generation sequencing (NGS) helps us to identify viruses without the design of a specific PCR primer. The major task in NGS data analysis is taxonomic identification for vast numbers of sequences. However, taxonomic identification via a BLAST search against all the known sequences is a computational bottleneck. DESCRIPTION: Here we propose an enhanced lowest-common-ancestor based method (ELM) to effectively identify viruses from massive sequence data. To reduce the computational cost, ELM uses a customized database composed only of viral sequences for the BLAST search. At the same time, ELM adopts a novel criterion to suppress the rise in false positive assignments caused by the small database. As a result, identification by ELM is more than 1,000 times faster than the conventional methods without loss of accuracy. CONCLUSIONS: We anticipate that ELM will contribute to direct diagnosis of viral infections. The web server and the customized viral database are freely available at http://bioinformatics.czc.hokudai.ac.jp/ELM/. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-254) contains supplementary material, which is available to authorized users.",2014 Jul 28,"['Ueno, Keisuke', 'Ishii, Akihiro', 'Ito, Kimihito']",BMC Bioinformatics,,,False
fd1910cd1f9847cf0b72bbcf0d94447807c9de66,PMC,ELM: enhanced lowest common ancestor based method for detecting a pathogenic virus from a large sequence dataset,http://dx.doi.org/10.1186/1471-2105-15-254,PMC4124145,25069839,CC BY,"BACKGROUND: Emerging viral diseases, most of which are caused by the transmission of viruses from animals to humans, pose a threat to public health. Discovering pathogenic viruses through surveillance is the key to preparedness for this potential threat. Next generation sequencing (NGS) helps us to identify viruses without the design of a specific PCR primer. The major task in NGS data analysis is taxonomic identification for vast numbers of sequences. However, taxonomic identification via a BLAST search against all the known sequences is a computational bottleneck. DESCRIPTION: Here we propose an enhanced lowest-common-ancestor based method (ELM) to effectively identify viruses from massive sequence data. To reduce the computational cost, ELM uses a customized database composed only of viral sequences for the BLAST search. At the same time, ELM adopts a novel criterion to suppress the rise in false positive assignments caused by the small database. As a result, identification by ELM is more than 1,000 times faster than the conventional methods without loss of accuracy. CONCLUSIONS: We anticipate that ELM will contribute to direct diagnosis of viral infections. The web server and the customized viral database are freely available at http://bioinformatics.czc.hokudai.ac.jp/ELM/. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-254) contains supplementary material, which is available to authorized users.",2014 Jul 28,"['Ueno, Keisuke', 'Ishii, Akihiro', 'Ito, Kimihito']",BMC Bioinformatics,,,True
4826b9556f50d690979be891d770b33e25003440,PMC,Update in Pathogenesis and Prospective in Treatment of Necrotizing Enterocolitis,http://dx.doi.org/10.1155/2014/543765,PMC4124648,25147804,CC BY,"Necrotizing enterocolitis (NEC) is among the most common and devastating diseases in neonates and, despite the significant advances in neonatal clinical and basic science investigations, its etiology is largely understood, specific treatment strategies are lacking, and morbidity and mortality remain high. Improvements in the understanding of pathogenesis of NEC may have therapeutic consequences. Pharmacologic inhibition of toll-like receptor signaling, the use of novel nutritional strategies, and microflora modulation may represent novel promising approaches to the prevention and treatment of NEC. This review, starting from the recent acquisitions in the pathogenic mechanisms of NEC, focuses on current and possible therapeutic perspectives.",2014 Jul 17,"['Terrin, Gianluca', 'Scipione, Antonella', 'De Curtis, Mario']",Biomed Res Int,,,True
2ee32c492fb088bca33f2b2409baa37d488dae5c,PMC,Virus-Specific Regulatory T Cells Ameliorate Encephalitis by Repressing Effector T Cell Functions from Priming to Effector Stages,http://dx.doi.org/10.1371/journal.ppat.1004279,PMC4125232,25102154,CC BY,"Several studies have demonstrated the presence of pathogen-specific Foxp3(+) CD4 regulatory T cells (Treg) in infected animals, but little is known about where and how these cells affect the effector T cell responses and whether they are more suppressive than bulk Treg populations. We recently showed the presence of both epitope M133-specific Tregs (M133 Treg) and conventional CD4 T cells (M133 Tconv) in the brains of mice with coronavirus-induced encephalitis. Here, we provide new insights into the interactions between pathogenic Tconv and Tregs responding to the same epitope. M133 Tregs inhibited the proliferation but not initial activation of M133 Tconv in draining lymph nodes (DLN). Further, M133 Tregs inhibited migration of M133 Tconv from the DLN. In addition, M133 Tregs diminished microglia activation and decreased the number and function of Tconv in the infected brain. Thus, virus-specific Tregs inhibited pathogenic CD4 T cell responses during priming and effector stages, particularly those recognizing cognate antigen, and decreased mortality and morbidity without affecting virus clearance. These cells are more suppressive than bulk Tregs and provide a targeted approach to ameliorating immunopathological disease in infectious settings.",2014 Aug 7,"['Zhao, Jingxian', 'Zhao, Jincun', 'Perlman, Stanley']",PLoS Pathog,,,True
526919a3d53c54d8c3d0d6b3ba24c77f3a665e1a,PMC,"Molecular Detection of Adenoviruses, Rhabdoviruses, and Paramyxoviruses in Bats from Kenya",http://dx.doi.org/10.4269/ajtmh.13-0664,PMC4125246,24865685,CC BY,"We screened 217 bats of at least 20 species from 17 locations in Kenya during July and August of 2006 for the presence of adenovirus, rhabdovirus, and paramyxovirus nucleic acids using generic reverse transcription polymerase chain reaction (RT-PCR) and PCR assays. Of 217 bat fecal swabs examined, 4 bats were adenovirus DNA-positive, 11 bats were paramyxovirus RNA-positive, and 2 bats were rhabdovirus RNA-positive. Three bats were coinfected by two different viruses. By sequence comparison and phylogenetic analysis, the Kenya bat paramyxoviruses and rhabdoviruses from this study may represent novel viral lineages within their respective families; the Kenya bat adenoviruses could not be confirmed as novel, because the same region sequences from other known bat adenovirus genomes for comparison were lacking. Our study adds to previous evidence that bats carry diverse, potentially zoonotic viruses and may be coinfected with more than one virus.",2014 Aug 6,"['Conrardy, Christina', 'Tao, Ying', 'Kuzmin, Ivan V.', 'Niezgoda, Michael', 'Agwanda, Bernard', 'Breiman, Robert F.', 'Anderson, Larry J.', 'Rupprecht, Charles E.', 'Tong, Suxiang']",Am J Trop Med Hyg,,,True
0a4ff36a0de0c6c9efdcc2f20e3223a31e4c05a0,PMC,Single detection of human bocavirus 1 with a high viral load in severe respiratory tract infections in previously healthy children,http://dx.doi.org/10.1186/1471-2334-14-424,PMC4125703,25078257,CC BY,"BACKGROUND: Human bocavirus is a newly discovered parvovirus. Multiple studies have confirmed the presence of human bocavirus1 (HBoV1) in respiratory tract samples of children. The viral load, presentation of single detection and its role as a causative agent of severe respiratory tract infections have not been thoroughly elucidated. METHODS: We investigated the presence of HBoV1 by quantitative polymerase chain reaction (PCR) of nasopharyngeal aspirate specimens from 1229 children hospitalized for respiratory tract infections. The samples were analyzed for 15 respiratory viruses by PCR and 7 respiratory viruses by viral culture. RESULTS: At least one virus was detected in 652 (53.1%) of 1229 children, and two or more viruses were detected in 266 (21.6%) children. HBoV1 was detected in 127 children (10.3%), in which 66/127 (52%) of the cases were the only HBoV1 virus detected. Seasonal variation was observed with a high HBoV1 infection rate in summer. A cutoff value of 10(7) copies/mL was used to distinguish high and low HBoV1 viral loads in the nasopharyngeal aspirates. High viral loads of HBoV1 were noted predominantly in the absence of other viral agents (28/39, 71.8%) whereas there was primarily co-detection in cases of low HBoV1 viral loads (50/88, 56.8%). There were no differences in the clinical symptoms and severity between HBoV1 single detection and co-detection. In cases of HBoV1 single detection, the high viral load group was more prevalent among children with dyspnea and wheezing than was the low viral load group (42.9% vs. 23.7%, P = 0.036; 60.7% vs. 31.6%, P = 0.018). In clinical severity, a significant difference was recorded (25.0% vs. 5.3%, P = 0.003) between high viral load and low viral load groups. Of the HBoV1 positive patients associated with severe respiratory tract infections, 10/18 (55.6%) patients belonged to the HBoV1 high viral load group, and 7/10 (70%) patients had cases of HBoV1 single detection. CONCLUSIONS: HBoV1 at a high viral load is not frequently found in co-detection with other respiratory viruses, and a single detection with a high viral load could be an etiological agent of severe respiratory tract infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-424) contains supplementary material, which is available to authorized users.",2014 Jul 30,"['Zhou, Lili', 'Zheng, Shouyan', 'Xiao, Qiuyan', 'Ren, Luo', 'Xie, Xiaohong', 'Luo, Jian', 'Wang, Lijia', 'Huang, Ailong', 'Liu, Wei', 'Liu, Enmei']",BMC Infect Dis,,,True
3128ce331b8e280214991a3c775c895045ccfa70,PMC,Anti-inflammatory effects of Lactococcus lactis NCDO 2118 during the remission period of chemically induced colitis,http://dx.doi.org/10.1186/1757-4749-6-33,PMC4126083,25110521,CC BY,"BACKGROUND: Many probiotic bacteria have been described as promising tools for the treatment and prevention of inflammatory bowel diseases (IBDs). Most of these bacteria are lactic acid bacteria, which are part of the healthy human microbiota. However, little is known about the effects of transient bacteria present in normal diets, including Lactococcus lactis. METHODS: In the present study, we analysed the immunomodulatory effects of three L. lactis strains in vitro using intestinal epithelial cells. L. lactis NCDO 2118 was administered for 4 days to C57BL/6 mice during the remission period of colitis induced by dextran sodium sulphate (DSS). RESULTS: Only one strain, L. lactis NCDO 2118, was able to reduce IL-1β-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect. Oral treatment using L. lactis NCDO 2118 resulted in a milder form of recurrent colitis than that observed in control diseased mice. This protective effect was not attributable to changes in secretory IgA (sIgA); however, NCDO 2118 administration was associated with an early increase in IL-6 production and sustained IL-10 production in colonic tissue. Mice fed L. lactis NCDO 2118 had an increased number of regulatory CD4(+) T cells (Tregs) bearing surface TGF-β in its latent form (Latency-associated peptide-LAP) in the mesenteric lymph nodes and spleen. CONCLUSIONS: Here, we identified a new probiotic strain with a potential role in the treatment of IBD, and we elucidated some of the mechanisms underlying its anti-inflammatory effect.",2014 Jul 29,"['Luerce, Tessalia Diniz', 'Gomes-Santos, Ana Cristina', 'Rocha, Clarissa Santos', 'Moreira, Thais Garcias', 'Cruz, Déborah Nogueira', 'Lemos, Luísa', 'Sousa, Adna Luciana', 'Pereira, Vanessa Bastos', 'de Azevedo, Marcela', 'Moraes, Kátia', 'Cara, Denise Carmona', 'LeBlanc, Jean Guy', 'Azevedo, Vasco', 'Faria, Ana Maria Caetano', 'Miyoshi, Anderson']",Gut Pathog,,,True
d887a0239eb93e1f9eed94d50126ba28157c4675,PMC,The impact of the interferon-lambda family on the innate and adaptive immune response to viral infections,http://dx.doi.org/10.1038/emi.2014.51,PMC4126180,26038748,CC BY,"Type-III interferons (IFN-λ, IFNL) are the most recently described family of IFNs. This family of innate cytokines are increasingly being ascribed pivotal roles in host–pathogen interactions. Herein, we will review the accumulating evidence detailing the immune biology of IFNL during viral infection, and the implications of this novel information on means to advance the development of therapies and vaccines against existing and emerging pathogens. IFNLs exert antiviral effects via induction of IFN-stimulated genes. Common single nucleotide polymorphisms (SNPs) in the IFNL3, IFNL4 and the IFNL receptor α-subunit genes have been strongly associated with IFN-α-based treatment of chronic hepatitis C virus infection. The clinical impact of these SNPs may be dependent on the status of viral infection (acute or chronic) and the potential to develop viral resistance. Another important function of IFNLs is macrophage and dendritic cell polarization, which prime helper T-cell activation and proliferation. It has been demonstrated that IFNL increase Th1- and reduce Th2-cytokines. Therefore, can such SNPs affect the IFNL signaling and thereby modulate the Th1/Th2 balance during infection? In turn, this may influence the subsequent priming of cytotoxic T cells versus antibody-secreting B cells, with implications for the breadth and durability of the host response.",2014 Jul 16,"['Egli, Adrian', 'Santer, Deanna M', ""O'Shea, Daire"", 'Tyrrell, D Lorne', 'Houghton, Michael']",Emerg Microbes Infect,,,True
cddbec166688aaf25aa6e2e6dc76a90668ba9e9d,PMC,A Membrane Topology Model for Human Interferon Inducible Transmembrane Protein 1,http://dx.doi.org/10.1371/journal.pone.0104341,PMC4126714,25105503,CC BY,"InterFeron Inducible TransMembrane proteins 1–3 (IFITM1, IFITM2 and IFITM3) are a family of proteins capable of inhibiting the cellular entry of numerous human and animal viruses. IFITM1-3 are unique amongst the currently described viral restriction factors in their apparent ability to block viral entry. This restrictive property is dependant on the localisation of the proteins to plasma and endosomal membranes, which constitute the main portals of viral entry into cells. The topology of the IFITM proteins within cell membranes is an unresolved aspect of their biology. Here we present data from immunofluorescence microscopy, protease cleavage, biotin-labelling and immuno-electron microscopy assays, showing that human IFITM1 has a membrane topology in which the N-terminal domain resides in the cytoplasm, and the C-terminal domain is extracellular. Furthermore, we provide evidence that this topology is conserved for all of the human interferon-induced IFITM proteins. This model is consistent with that recently proposed for murine IFITM3, but differs from that proposed for murine IFITM1.",2014 Aug 8,"['Weston, Stuart', 'Czieso, Stephanie', 'White, Ian J.', 'Smith, Sarah E.', 'Kellam, Paul', 'Marsh, Mark']",PLoS One,,,True
167b459cba8933f49d8cb5585f442a68fe326361,PMC,Cellular Proteins Associated with the Interior and Exterior of Vesicular Stomatitis Virus Virions,http://dx.doi.org/10.1371/journal.pone.0104688,PMC4126742,25105980,CC BY,"Virus particles (virions) often contain not only virus-encoded but also host-encoded proteins. Some of these host proteins are enclosed within the virion structure, while others, in the case of enveloped viruses, are embedded in the host-derived membrane. While many of these host protein incorporations are likely accidental, some may play a role in virus infectivity, replication and/or immunoreactivity in the next host. Host protein incorporations may be especially important in therapeutic applications where large numbers of virus particles are administered. Vesicular stomatitis virus (VSV) is the prototypic rhabdovirus and a candidate vaccine, gene therapy and oncolytic vector. Using mass spectrometry, we previously examined cell type dependent host protein content of VSV virions using intact (“whole”) virions purified from three cell lines originating from different species. Here we aimed to determine the localization of host proteins within the VSV virions by analyzing: i) whole VSV virions; and ii) whole VSV virions treated with Proteinase K to remove all proteins outside the viral envelope. A total of 257 proteins were identified, with 181 identified in whole virions and 183 identified in Proteinase K treated virions. Most of these proteins have not been previously shown to be associated with VSV. Functional enrichment analysis indicated the most overrepresented categories were proteins associated with vesicles, vesicle-mediated transport and protein localization. Using western blotting, the presence of several host proteins, including some not previously shown in association with VSV (such as Yes1, Prl1 and Ddx3y), was confirmed and their relative quantities in various virion fractions determined. Our study provides a valuable inventory of virion-associated host proteins for further investigation of their roles in the replication cycle, pathogenesis and immunoreactivity of VSV.",2014 Aug 8,"['Moerdyk-Schauwecker, Megan', 'Hwang, Sun-Il', 'Grdzelishvili, Valery Z.']",PLoS One,,,True
c8adc8df36e5301e6455b55be70e3164b9de66a7,PMC,The Consequences of a Lab Escape of a Potential Pandemic Pathogen,http://dx.doi.org/10.3389/fpubh.2014.00116,PMC4128296,25157347,CC BY,,2014 Aug 11,"['Klotz, Lynn C.', 'Sylvester, Edward J.']",Front Public Health,,,True
5c8323be8a418f5df5d877da4a51720e9aa60425,PMC,Herpes simplex virus type 1 and Alzheimer’s disease: increasing evidence for a major role of the virus,http://dx.doi.org/10.3389/fnagi.2014.00202,PMC4128394,25157230,CC BY,"Herpes simplex virus type 1 (HSV1), when present in brain of carriers of the type 4 allele of the apolipoprotein E gene (APOE), has been implicated as a major factor in Alzheimer’s disease (AD). It is proposed that virus is normally latent in many elderly brains but reactivates periodically (as in the peripheral nervous system) under certain conditions, for example stress, immunosuppression, and peripheral infection, causing cumulative damage and eventually development of AD. Diverse approaches have provided data that explicitly support, directly or indirectly, these concepts. Several have confirmed HSV1 DNA presence in human brains, and the HSV1-APOE-ε4 association in AD. Further, studies on HSV1-infected APOE-transgenic mice have shown that APOE-e4 animals display a greater potential for viral damage. Reactivated HSV1 can cause direct and inflammatory damage, probably involving increased formation of beta amyloid (Aβ) and of AD-like tau (P-tau)—changes found to occur in HSV1-infected cell cultures. Implicating HSV1 further in AD is the discovery that HSV1 DNA is specifically localized in amyloid plaques in AD. Other relevant, harmful effects of infection include the following: dynamic interactions between HSV1 and amyloid precursor protein (APP), which would affect both viral and APP transport; induction of toll-like receptors (TLRs) in HSV1-infected astrocyte cultures, which has been linked to the likely effects of reactivation of the virus in brain. Several epidemiological studies have shown, using serological data, an association between systemic infections and cognitive decline, with HSV1 particularly implicated. Genetic studies too have linked various pathways in AD with those occurring on HSV1 infection. In relation to the potential usage of antivirals to treat AD patients, acyclovir (ACV) is effective in reducing HSV1-induced AD-like changes in cell cultures, and valacyclovir, the bioactive form of ACV, might be most effective if combined with an antiviral that acts by a different mechanism, such as intravenous immunoglobulin (IVIG).",2014 Aug 11,"Itzhaki, Ruth F.",Front Aging Neurosci,,,True
6f6da38ab5fa77f94deb29bfa51504be4ebd018b,PMC,Chinese patent medicines for the treatment of the common cold: a systematic review of randomized clinical trials,http://dx.doi.org/10.1186/1472-6882-14-273,PMC4129119,25074623,CC BY,"BACKGROUND: Many Chinese patent medicines (CPMs) have been authorized by the Chinese State of Food and Drug Administration for the treatment of the common cold. A number of clinical trials have been conducted and published. However, there is no systematic review or meta-analysis on their efficacy and safety for the common cold to justify their clinical use. METHODS: We searched CENTRAL, MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites for published and unpublished randomized clinical trials (RCTs) of CPMs for the common cold till 31 March 2013. Revman 5.2 software was used for data analysis with effect estimate presented as relative risk (RR) and mean difference (MD) with a 95% confidence interval (CI). RESULTS: A total of five RCTs were identified. All of the RCTs were of high risk of bias with flawed study design and poor methodological quality. All RCTs included children aged between 6 months to 14 years. Results of individual trials showed that Shuanghuanglian oral liquid (RR 4.00; 95% CI: 2.26 to 7.08), and Xiaoer Resuqing oral liquid (RR 1.43; 95% CI: 1.15 to 1.77) had higher cure rates compared with antivirus drugs. Most of the trials did not report adverse events, and the safety of CPMs was still uncertain. CONCLUSIONS: Some CPMs showed a potential positive effect for the common cold on cure rate. However, due to the poor methodology quality and the defects in the clinical design of the included RCTs, such as the lack of placebo controlled trials, the inappropriate comparison intervention and outcome measurement, the confirmative conclusions on the beneficial effect of CPMs for the common cold could not be drawn.",2014 Jul 30,"['Chen, Wei', 'Liu, Bo', 'Wang, Li-qiong', 'Ren, Jun', 'Liu, Jian-ping']",BMC Complement Altern Med,,,True
f4c43e4ae49ca69dbac32620bd0a73ecbb683b91,PMC,Exploring the Innate Immunological Response of an Alternative Nonhuman Primate Model of Infectious Disease; the Common Marmoset,http://dx.doi.org/10.1155/2014/913632,PMC4129158,25170519,CC BY,"The common marmoset (Callithrix jacchus) is increasingly being utilised as a nonhuman primate model for human disease, ranging from autoimmune to infectious disease. In order to fully exploit these models, meaningful comparison to the human host response is necessary. Commercially available reagents, primarily targeted to human cells, were utilised to assess the phenotype and activation status of key immune cell types and cytokines in naive and infected animals. Single cell suspensions of blood, spleen, and lung were examined. Generally, the phenotype of cells was comparable between humans and marmosets, with approximately 63% of all lymphocytes in the blood of marmosets being T cells, 25% B-cells, and 12% NK cells. The percentage of neutrophils in marmoset blood were more similar to human values than mouse values. Comparison of the activation status of cells following experimental systemic or inhalational infection exhibited different trends in different tissues, most obvious in cell types active in the innate immune response. This work significantly enhances the ability to understand the immune response in these animals and fortifies their use as models of infectious disease.",2014 Jul 22,"['Nelson, M.', 'Loveday, M.']",J Immunol Res,,,True
4ceca734c7185a61184a7e464e454b7f7d958dba,PMC,"Etiology of Severe Childhood Pneumonia in The Gambia, West Africa, Determined by Conventional and Molecular Microbiological Analyses of Lung and Pleural Aspirate Samples",http://dx.doi.org/10.1093/cid/ciu384,PMC4130311,24867789,CC BY,"Molecular analyses of lung aspirates from Gambian children with severe pneumonia detected pathogens more frequently than did culture and showed a predominance of bacteria, principally Streptococcus pneumoniae, >75% being of serotypes covered by current pneumococcal conjugate vaccines. Multiple pathogens were detected frequently, notably Haemophilus influenzae (mostly nontypeable) together with S. pneumoniae.",2014 Sep 1,"['Howie, Stephen R. C.', 'Morris, Gerard A. J.', 'Tokarz, Rafal', 'Ebruke, Bernard E.', 'Machuka, Eunice M.', 'Ideh, Readon C.', 'Chimah, Osaretin', 'Secka, Ousman', 'Townend, John', 'Dione, Michel', 'Oluwalana, Claire', 'Njie, Malick', 'Jallow, Mariatou', 'Hill, Philip C.', 'Antonio, Martin', 'Greenwood, Brian', 'Briese, Thomas', 'Mulholland, Kim', 'Corrah, Tumani', 'Lipkin, W. Ian', 'Adegbola, Richard A.']",Clin Infect Dis,,,True
70f3c90a651224f9292378da905af4ec635d5f43,PMC,Need of surveillance response systems to combat Ebola outbreaks and other emerging infectious diseases in African countries,http://dx.doi.org/10.1186/2049-9957-3-29,PMC4130433,25120913,CC BY,"There is growing concern in Sub-Saharan Africa about the spread of the Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, and the public health burden that it ensues. Since 1976, there have been 885,343 suspected and laboratory confirmed cases of EVD and the disease has claimed 2,512 cases and 932 fatality in West Africa. There are certain requirements that must be met when responding to EVD outbreaks and this process could incur certain challenges. For the purposes of this paper, five have been identified: (i) the deficiency in the development and implementation of surveillance response systems against Ebola and others infectious disease outbreaks in Africa; (ii) the lack of education and knowledge resulting in an EVD outbreak triggering panic, anxiety, psychosocial trauma, isolation and dignity impounding, stigmatisation, community ostracism and resistance to associated socio-ecological and public health consequences; (iii) limited financial resources, human technical capacity and weak community and national health system operational plans for prevention and control responses, practices and management; (iv) inadequate leadership and coordination; and (v) the lack of development of new strategies, tools and approaches, such as improved diagnostics and novel therapies including vaccines which can assist in preventing, controlling and containing Ebola outbreaks as well as the spread of the disease. Hence, there is an urgent need to develop and implement an active early warning alert and surveillance response system for outbreak response and control of emerging infectious diseases. Understanding the unending risks of transmission dynamics and resurgence is essential in implementing rapid effective response interventions tailored to specific local settings and contexts. Therefore, the following actions are recommended: (i) national and regional inter-sectorial and trans-disciplinary surveillance response systems that include early warnings, as well as critical human resources development, must be quickly adopted by allied ministries and organisations in African countries in epidemic and pandemic responses; (ii) harnessing all stakeholders commitment and advocacy in sustained funding, collaboration, communication and networking including community participation to enhance a coordinated responses, as well as tracking and prompt case management to combat challenges; (iii) more research and development in new drug discovery and vaccines; and (iv) understanding the involvement of global health to promote the establishment of public health surveillance response systems with functions of early warning, as well as monitoring and evaluation in upholding research-action programmes and innovative interventions.",2014 Aug 5,"['Tambo, Ernest', 'Ugwu, Emmanuel Chidiebere', 'Ngogang, Jeane Yonkeu']",Infect Dis Poverty,,,True
7b4eded72a4f06ae298b78f07953e3f45f853aa3,PMC,Need of surveillance response systems to combat Ebola outbreaks and other emerging infectious diseases in African countries,http://dx.doi.org/10.1186/2049-9957-3-29,PMC4130433,25120913,CC BY,"There is growing concern in Sub-Saharan Africa about the spread of the Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, and the public health burden that it ensues. Since 1976, there have been 885,343 suspected and laboratory confirmed cases of EVD and the disease has claimed 2,512 cases and 932 fatality in West Africa. There are certain requirements that must be met when responding to EVD outbreaks and this process could incur certain challenges. For the purposes of this paper, five have been identified: (i) the deficiency in the development and implementation of surveillance response systems against Ebola and others infectious disease outbreaks in Africa; (ii) the lack of education and knowledge resulting in an EVD outbreak triggering panic, anxiety, psychosocial trauma, isolation and dignity impounding, stigmatisation, community ostracism and resistance to associated socio-ecological and public health consequences; (iii) limited financial resources, human technical capacity and weak community and national health system operational plans for prevention and control responses, practices and management; (iv) inadequate leadership and coordination; and (v) the lack of development of new strategies, tools and approaches, such as improved diagnostics and novel therapies including vaccines which can assist in preventing, controlling and containing Ebola outbreaks as well as the spread of the disease. Hence, there is an urgent need to develop and implement an active early warning alert and surveillance response system for outbreak response and control of emerging infectious diseases. Understanding the unending risks of transmission dynamics and resurgence is essential in implementing rapid effective response interventions tailored to specific local settings and contexts. Therefore, the following actions are recommended: (i) national and regional inter-sectorial and trans-disciplinary surveillance response systems that include early warnings, as well as critical human resources development, must be quickly adopted by allied ministries and organisations in African countries in epidemic and pandemic responses; (ii) harnessing all stakeholders commitment and advocacy in sustained funding, collaboration, communication and networking including community participation to enhance a coordinated responses, as well as tracking and prompt case management to combat challenges; (iii) more research and development in new drug discovery and vaccines; and (iv) understanding the involvement of global health to promote the establishment of public health surveillance response systems with functions of early warning, as well as monitoring and evaluation in upholding research-action programmes and innovative interventions.",2014 Aug 5,"['Tambo, Ernest', 'Ugwu, Emmanuel Chidiebere', 'Ngogang, Jeane Yonkeu']",Infect Dis Poverty,,,False
108b012df7e6ae774a2a83243c0662f376637426,PMC,Porcine Epidemic Diarrhea Virus RNA Present in Commercial Spray-Dried Porcine Plasma Is Not Infectious to Naïve Pigs,http://dx.doi.org/10.1371/journal.pone.0104766,PMC4130536,25116479,CC BY,"Porcine epidemic diarrhea virus emerged in North America in April 2013 and has since been identified in 30 U.S. States, Canada and Mexico. The rapid spread of PEDV has raised concerns about the role of feed and particularly pork-by-product components such as spray-dried porcine plasma (SDPP) in PEDV transmission. The aim of this study was to determine the infectivity of PEDV RNA present in commercial SDPP. Specifically, 40 3-week-old PEDV naïve pigs were randomly assigned to one of five treatment groups. At day post inoculation (dpi) 0, NEG-CONTROL pigs were sham-inoculated, PEDV-CONTROL pigs received cell culture propagated PEDV, and SDPP-CONTROL pigs were switched to a diet with 5% SDPP containing 5.1±0.1 log(10) PEDV RNA copies/g. To evaluate a potential positive effect of anti-PEDV antibodies in SDPP on PEDV challenge, four days prior to PEDV challenge the pigs in the SDPP-PEDV group were switched to and remained on a 5% SDPP diet through dpi 28. Another group, EGG-PEDV, was orally administered a commercial egg-derived liquid PEDV globulin product from dpi -4 through 6. All PEDV-CONTROL pigs began shedding PEDV in feces by dpi 3 and seroconverted between dpi 7 and 14, whereas pigs in NEG-CONTROL and SDPP-CONTROL groups remained PEDV RNA negative and did not seroconvert to PEDV for the study duration. This indicates no evidence of infectivity of the PEDV RNA in the SDPP lot utilized. Furthermore, under the study conditions SDPP or egg-derived liquid PEDV globulin addition did not significantly alter PEDV-shedding or overall disease course after experimental challenge.",2014 Aug 12,"['Opriessnig, Tanja', 'Xiao, Chao-Ting', 'Gerber, Priscilla F.', 'Zhang, Jianqiang', 'Halbur, Patrick G.']",PLoS One,,,True
21469fd00f33c1dcdde68abf4b8da0508b7fe2d8,PMC,Self-Assembly and Release of Peste des Petits Ruminants Virus-Like Particles in an Insect Cell-Baculovirus System and Their Immunogenicity in Mice and Goats,http://dx.doi.org/10.1371/journal.pone.0104791,PMC4130610,25117931,CC BY,"Peste des petits ruminants (PPR) is an acute, febrile, viral disease of small ruminants that has a significant economic impact. For many viral diseases, vaccination with virus-like particles (VLPs) has shown considerable promise as a prophylactic approach; however, the processes of assembly and release of peste des petits ruminants virus (PPRV) VLPs are not well characterized, and their immunogenicity in the host is unknown. In this study, VLPs of PPRV were generated in a baculovirus system through simultaneous expression of PPRV matrix (M) protein and hemaglutin in (H) or fusion (F) protein. The released VLPs showed morphology similar to that of the native virus particles. Subcutaneous injection of these VLPs (PPRV-H, PPRV-F) into mice and goats elicited PPRV-specific IgG production, increased the levels of virus neutralizing antibodies, and promoted lymphocyte proliferation. Without adjuvants, the immune response induced by the PPRV-H VLPs was comparable to that obtained using equivalent amounts of PPRV vaccine. Thus, our results demonstrated that VLPs containing PPRV M protein and H or F protein are potential “differentiating infected from vaccinated animals” (DIVA) vaccine candidates for the surveillance and eradication of PPR.",2014 Aug 12,"['Li, Wenchao', 'Jin, Hongyan', 'Sui, Xiukun', 'Zhao, Zhanzhong', 'Yang, Chenghuai', 'Wang, Wenquan', 'Li, Junping', 'Li, Gang']",PLoS One,,,True
8dada285162e466f7867f6b657853905bd778933,PMC,Using core competencies to build an evaluative framework: outcome assessment of the University of Guelph Master of Public Health program,http://dx.doi.org/10.1186/1472-6920-14-158,PMC4131476,25078124,CC BY,"BACKGROUND: Master of Public Health programs have been developed across Canada in response to the need for graduate-level trained professionals to work in the public health sector. The University of Guelph recently conducted a five-year outcome assessment using the Core Competencies for Public Health in Canada as an evaluative framework to determine whether graduates are receiving adequate training, and identify areas for improvement. METHODS: A curriculum map of core courses and an online survey of University of Guelph Master of Public Health graduates comprised the outcome assessment. The curriculum map was constructed by evaluating course outlines, assignments, and content to determine the extent to which the Core Competencies were covered in each course. Quantitative survey results were characterized using descriptive statistics. Qualitative survey results were analyzed to identify common themes and patterns in open-ended responses. RESULTS: The University of Guelph Master of Public Health program provided a positive learning environment in which graduates gained proficiency across the Core Competencies through core and elective courses, meaningful practicums, and competent faculty. Practice-based learning environments, particularly in collaboration with public health organizations, were deemed to be beneficial to students’ learning experiences. CONCLUSIONS: The Core Competencies and graduate surveys can be used to conduct a meaningful and informative outcome assessment. We encourage other Master of Public Health programs to conduct their own outcome assessments using a similar framework, and disseminate these results in order to identify best practices and strengthen the Canadian graduate public health education system.",2014 Jul 31,"['Britten, Nicole', 'Wallar, Lauren E', 'McEwen, Scott A', 'Papadopoulos, Andrew']",BMC Med Educ,,,True
af86dce0ad626fff251552974a6b9245a0038e14,PMC,Using core competencies to build an evaluative framework: outcome assessment of the University of Guelph Master of Public Health program,http://dx.doi.org/10.1186/1472-6920-14-158,PMC4131476,25078124,CC BY,"BACKGROUND: Master of Public Health programs have been developed across Canada in response to the need for graduate-level trained professionals to work in the public health sector. The University of Guelph recently conducted a five-year outcome assessment using the Core Competencies for Public Health in Canada as an evaluative framework to determine whether graduates are receiving adequate training, and identify areas for improvement. METHODS: A curriculum map of core courses and an online survey of University of Guelph Master of Public Health graduates comprised the outcome assessment. The curriculum map was constructed by evaluating course outlines, assignments, and content to determine the extent to which the Core Competencies were covered in each course. Quantitative survey results were characterized using descriptive statistics. Qualitative survey results were analyzed to identify common themes and patterns in open-ended responses. RESULTS: The University of Guelph Master of Public Health program provided a positive learning environment in which graduates gained proficiency across the Core Competencies through core and elective courses, meaningful practicums, and competent faculty. Practice-based learning environments, particularly in collaboration with public health organizations, were deemed to be beneficial to students’ learning experiences. CONCLUSIONS: The Core Competencies and graduate surveys can be used to conduct a meaningful and informative outcome assessment. We encourage other Master of Public Health programs to conduct their own outcome assessments using a similar framework, and disseminate these results in order to identify best practices and strengthen the Canadian graduate public health education system.",2014 Jul 31,"['Britten, Nicole', 'Wallar, Lauren E', 'McEwen, Scott A', 'Papadopoulos, Andrew']",BMC Med Educ,,,False
76121941b87c781e6bdb9872304d87a74cc0f782,PMC,Using core competencies to build an evaluative framework: outcome assessment of the University of Guelph Master of Public Health program,http://dx.doi.org/10.1186/1472-6920-14-158,PMC4131476,25078124,CC BY,"BACKGROUND: Master of Public Health programs have been developed across Canada in response to the need for graduate-level trained professionals to work in the public health sector. The University of Guelph recently conducted a five-year outcome assessment using the Core Competencies for Public Health in Canada as an evaluative framework to determine whether graduates are receiving adequate training, and identify areas for improvement. METHODS: A curriculum map of core courses and an online survey of University of Guelph Master of Public Health graduates comprised the outcome assessment. The curriculum map was constructed by evaluating course outlines, assignments, and content to determine the extent to which the Core Competencies were covered in each course. Quantitative survey results were characterized using descriptive statistics. Qualitative survey results were analyzed to identify common themes and patterns in open-ended responses. RESULTS: The University of Guelph Master of Public Health program provided a positive learning environment in which graduates gained proficiency across the Core Competencies through core and elective courses, meaningful practicums, and competent faculty. Practice-based learning environments, particularly in collaboration with public health organizations, were deemed to be beneficial to students’ learning experiences. CONCLUSIONS: The Core Competencies and graduate surveys can be used to conduct a meaningful and informative outcome assessment. We encourage other Master of Public Health programs to conduct their own outcome assessments using a similar framework, and disseminate these results in order to identify best practices and strengthen the Canadian graduate public health education system.",2014 Jul 31,"['Britten, Nicole', 'Wallar, Lauren E', 'McEwen, Scott A', 'Papadopoulos, Andrew']",BMC Med Educ,,,False
b9440a58f12e8325569e686c0aaf6eed458075ba,PMC,Using core competencies to build an evaluative framework: outcome assessment of the University of Guelph Master of Public Health program,http://dx.doi.org/10.1186/1472-6920-14-158,PMC4131476,25078124,CC BY,"BACKGROUND: Master of Public Health programs have been developed across Canada in response to the need for graduate-level trained professionals to work in the public health sector. The University of Guelph recently conducted a five-year outcome assessment using the Core Competencies for Public Health in Canada as an evaluative framework to determine whether graduates are receiving adequate training, and identify areas for improvement. METHODS: A curriculum map of core courses and an online survey of University of Guelph Master of Public Health graduates comprised the outcome assessment. The curriculum map was constructed by evaluating course outlines, assignments, and content to determine the extent to which the Core Competencies were covered in each course. Quantitative survey results were characterized using descriptive statistics. Qualitative survey results were analyzed to identify common themes and patterns in open-ended responses. RESULTS: The University of Guelph Master of Public Health program provided a positive learning environment in which graduates gained proficiency across the Core Competencies through core and elective courses, meaningful practicums, and competent faculty. Practice-based learning environments, particularly in collaboration with public health organizations, were deemed to be beneficial to students’ learning experiences. CONCLUSIONS: The Core Competencies and graduate surveys can be used to conduct a meaningful and informative outcome assessment. We encourage other Master of Public Health programs to conduct their own outcome assessments using a similar framework, and disseminate these results in order to identify best practices and strengthen the Canadian graduate public health education system.",2014 Jul 31,"['Britten, Nicole', 'Wallar, Lauren E', 'McEwen, Scott A', 'Papadopoulos, Andrew']",BMC Med Educ,,,False
4c9d7e3db46a6026e1554f2fa3df4f93645381e1,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,True
0863338d4ec43e14a5438e5935bea4ff7cebeba0,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
49f04c6a31256ab8fb38bdcc329a6744248287fe,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
90d84b5b33ae2fb3c8d04b2ddb22d38fc9812740,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
87b5b5ddaa9c4adce29690c99a8aa92ff94c9203,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
e3ced319adf75d3a8442f1f94aaa5e79f9c74a99,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
25e667ff5a9a2b7f23192c2d34ef8edef4831c3d,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
b9d414deb6745c5410577dd00a9a483f65e4b340,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
2e6cb10cda7335535d59ea42b3d1e61f8eb4d8b6,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
d57b9b3170641624374a5a8211179699202adade,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
729870e5682b37d66e76f187a00584d00f725ea8,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
ebc78f92bc422103204b417df443754c8bf11ed4,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
fd421b0d1a42db7b23a87c7c7fb668d54437d70a,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
f7adc8de97c5f8d8ab6f6cad71bbef9c50790629,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
e9b657e17fc500733811c3cdb06bf6da3fb2adc3,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
ef43f8ba1afa11245e1f85c36bf74f4640ac4f1f,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
674aee78f478c1b628f00b9824de6230585be142,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
cddb100b1e41224a63a2362be678d773426b4615,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
7e8e7ba9af4f10d5ec6bfda422d0f5251a5f0f2b,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
4aa3212174a384b9e1b5bd2f58023d60b1d1bd2d,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
49369bef87aedbc56dc328357faae0db1a40a517,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
36e5a1e939633cc6a8b4fa2dc7d70f9dbe5f0ee8,PMC,Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression,http://dx.doi.org/10.1534/g3.114.011759,PMC4132174,24902603,CC BY,"Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.",2014 Jun 5,"['Xiong, Hao', 'Morrison, Juliet', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Whitmore, Alan C.', 'Green, Richard', 'Thomas, Matthew J.', 'Tisoncik-Go, Jennifer', 'Schroth, Gary P.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.', 'Heise, Mark T.', 'Peng, Xinxia', 'Katze, Michael G.']",G3 (Bethesda),,,False
767767546b54da4b2a51840674c68adfd4e1a0bf,PMC,Detection of Middle East respiratory syndrome coronavirus using reverse transcription loop-mediated isothermal amplification (RT-LAMP),http://dx.doi.org/10.1186/1743-422X-11-139,PMC4132226,25103205,CC BY,"BACKGROUND: The first documented case of Middle East Respiratory Syndrome coronavirus (MERS-CoV) occurred in 2012, and outbreaks have continued ever since, mainly in Saudi Arabia. MERS-CoV is primarily diagnosed using a real-time RT-PCR assay, with at least two different genomic targets required for a positive diagnosis according to the case definition of The World Health Organization (WHO) as of 3 July 2013. Therefore, it is urgently necessary to develop as many specific genetic diagnostic methods as possible to allow stable diagnosis of MERS-CoV infections. METHODS: Reverse transcription-loop-mediated isothermal amplification (RT-LAMP) is a genetic diagnostic method used widely for the detection of viral pathogens, which requires only a single temperature for amplification, and can be completed in less than 1 h. This study developed a novel RT-LAMP assay for detecting MERS-CoV using primer sets targeting a conserved nucleocapsid protein region. RESULTS: The RT-LAMP assay was capable of detecting as few as 3.4 copies of MERS-CoV RNA, and was highly specific, with no cross-reaction to other respiratory viruses. Pilot experiments to detect MERS-CoV from medium containing pharyngeal swabs inoculated with pre-titrated viruses were also performed. The RT-LAMP assay exhibited sensitivity similar to that of MERS-CoV real-time RT-PCR. CONCLUSIONS: These results suggest that the RT-LAMP assay described here is a useful tool for the diagnosis and epidemiologic surveillance of human MERS-CoV infections.",2014 Aug 8,"['Shirato, Kazuya', 'Yano, Takuya', 'Senba, Syouhei', 'Akachi, Shigehiro', 'Kobayashi, Takashi', 'Nishinaka, Takamichi', 'Notomi, Tsugunori', 'Matsuyama, Shutoku']",Virol J,,,True
5bc94c9cd8e4bcae0c56a4343f6f60cdc0effa9c,PMC,Complete Genome Sequence of Porcine Epidemic Diarrhea Virus in Vietnam,http://dx.doi.org/10.1128/genomeA.00753-14,PMC4132615,25125639,CC BY,"Porcine epidemic diarrhea virus (PEDV) has emerged in Vietnam since 2009. Herein, full-length genome sequences are reported for three PEDV isolates from pigs displaying severe diarrhea from farms located in northern and southern provinces of Vietnam. The results provide more understanding of the molecular characteristics of PEDV in Vietnam.",2014 Aug 14,"['Vui, Dam Thi', 'Tung, Nguyen', 'Inui, Ken', 'Slater, Steven', 'Nilubol, Dachrit']",Genome Announc,,,True
7c36bbbb2505c7eefacad040c39bd5b167969ad2,PMC,The PDZ-Binding Motif of Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Is a Determinant of Viral Pathogenesis,http://dx.doi.org/10.1371/journal.ppat.1004320,PMC4133396,25122212,CC BY,"A recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ-binding motif (PBM), a domain involved in protein-protein interactions, is a major determinant of virulence. Elimination of SARS-CoV E protein PBM by using reverse genetics caused a reduction in the deleterious exacerbation of the immune response triggered during infection with the parental virus and virus attenuation. Cellular protein syntenin was identified to bind the E protein PBM during SARS-CoV infection by using three complementary strategies, yeast two-hybrid, reciprocal coimmunoprecipitation and confocal microscopy assays. Syntenin redistributed from the nucleus to the cell cytoplasm during infection with viruses containing the E protein PBM, activating p38 MAPK and leading to the overexpression of inflammatory cytokines. Silencing of syntenin using siRNAs led to a decrease in p38 MAPK activation in SARS-CoV infected cells, further reinforcing their functional relationship. Active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM as compared with the parental virus, leading to a decreased expression of inflammatory cytokines and to virus attenuation. Interestingly, administration of a p38 MAPK inhibitor led to an increase in mice survival after infection with SARS-CoV, confirming the relevance of this pathway in SARS-CoV virulence. Therefore, the E protein PBM is a virulence domain that activates immunopathology most likely by using syntenin as a mediator of p38 MAPK induced inflammation.",2014 Aug 14,"['Jimenez-Guardeño, Jose M.', 'Nieto-Torres, Jose L.', 'DeDiego, Marta L.', 'Regla-Nava, Jose A.', 'Fernandez-Delgado, Raul', 'Castaño-Rodriguez, Carlos', 'Enjuanes, Luis']",PLoS Pathog,,,True
298ebce4397c9735f69cb5fcf9ad82881eead18f,PMC,The HIV-1 Envelope Transmembrane Domain Binds TLR2 through a Distinct Dimerization Motif and Inhibits TLR2-Mediated Responses,http://dx.doi.org/10.1371/journal.ppat.1004248,PMC4133399,25121610,CC BY,"HIV-1 uses a number of means to manipulate the immune system, to avoid recognition and to highjack signaling pathways. HIV-1 infected cells show limited Toll-Like Receptor (TLR) responsiveness via as yet unknown mechanisms. Using biochemical and biophysical approaches, we demonstrate that the trans-membrane domain (TMD) of the HIV-1 envelope (ENV) directly interacts with TLR2 TMD within the membrane milieu. This interaction attenuates TNFα, IL-6 and MCP-1 secretion in macrophages, induced by natural ligands of TLR2 both in in vitro and in vivo models. This was associated with decreased levels of ERK phosphorylation. Furthermore, mutagenesis demonstrated the importance of a conserved GxxxG motif in driving this interaction within the membrane milieu. The administration of the ENV TMD in vivo to lipotechoic acid (LTA)/Galactosamine-mediated septic mice resulted in a significant decrease in mortality and in tissue damage, due to the weakening of systemic macrophage activation. Our findings suggest that the TMD of ENV is involved in modulation of the innate immune response during HIV infection. Furthermore, due to the high functional homology of viral ENV proteins this function may be a general character of viral-induced immune modulation.",2014 Aug 14,"['Reuven, Eliran Moshe', 'Ali, Mohammad', 'Rotem, Etai', 'Schwarzter, Roland', 'Gramatica, Andrea', 'Futerman, Anthony H.', 'Shai, Yechiel']",PLoS Pathog,,,True
a4e41dcddb7c0eb538defbf19602371176f1f97c,PMC,Effect of human movement on airborne disease transmission in an airplane cabin: study using numerical modeling and quantitative risk analysis,http://dx.doi.org/10.1186/1471-2334-14-434,PMC4133625,25098254,CC BY,"BACKGROUND: Airborne transmission of respiratory infectious disease in indoor environment (e.g. airplane cabin, conference room, hospital, isolated room and inpatient ward) may cause outbreaks of infectious diseases, which may lead to many infection cases and significantly influences on the public health. This issue has received more and more attentions from academics. This work investigates the influence of human movement on the airborne transmission of respiratory infectious diseases in an airplane cabin by using an accurate human model in numerical simulation and comparing the influences of different human movement behaviors on disease transmission. METHODS: The Eulerian–Lagrangian approach is adopted to simulate the dispersion and deposition of the expiratory aerosols. The dose–response model is used to assess the infection risks of the occupants. The likelihood analysis is performed as a hypothesis test on the input parameters and different human movement pattern assumptions. An in-flight SARS outbreak case is used for investigation. A moving person with different moving speeds is simulated to represent the movement behaviors. A digital human model was used to represent the detailed profile of the occupants, which was obtained by scanning a real thermal manikin using the 3D laser scanning system. RESULTS: The analysis results indicate that human movement can strengthen the downward transport of the aerosols, significantly reduce the overall deposition and removal rate of the suspended aerosols and increase the average infection risk in the cabin. The likelihood estimation result shows that the risk assessment results better fit the outcome of the outbreak case when the movements of the seated passengers are considered. The intake fraction of the moving person is significantly higher than most of the seated passengers. CONCLUSIONS: The infection risk distribution in the airplane cabin highly depends on the movement behaviors of the passengers and the index patient. The walking activities of the crew members and the seated passengers can significantly increase their personal infection risks. Taking the influence of the movement of the seated passengers and the index patient into consideration is necessary and important. For future studies, investigations on the behaviors characteristics of the passengers during flight will be useful and helpful for infection control. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-434) contains supplementary material, which is available to authorized users.",2014 Aug 6,"['Han, Zhuyang', 'Sze To, Gin Nam', 'Fu, Sau Chung', 'Chao, Christopher Yu-Hang', 'Weng, Wenguo', 'Huang, Quanyi']",BMC Infect Dis,,,True
692fedb674101b505fb28fe7b96e552ed224c07d,PMC,Multiplex Degenerate Primer Design for Targeted Whole Genome Amplification of Many Viral Genomes,http://dx.doi.org/10.1155/2014/101894,PMC4137498,25157264,CC BY,"Background. Targeted enrichment improves coverage of highly mutable viruses at low concentration in complex samples. Degenerate primers that anneal to conserved regions can facilitate amplification of divergent, low concentration variants, even when the strain present is unknown. Results. A tool for designing multiplex sets of degenerate sequencing primers to tile overlapping amplicons across multiple whole genomes is described. The new script, run_tiled_primers, is part of the PriMux software. Primers were designed for each segment of South American hemorrhagic fever viruses, tick-borne encephalitis, Henipaviruses, Arenaviruses, Filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, and Japanese encephalitis virus. Each group is highly diverse with as little as 5% genome consensus. Primer sets were computationally checked for nontarget cross reactions against the NCBI nucleotide sequence database. Primers for murine hepatitis virus were demonstrated in the lab to specifically amplify selected genes from a laboratory cultured strain that had undergone extensive passage in vitro and in vivo. Conclusions. This software should help researchers design multiplex sets of primers for targeted whole genome enrichment prior to sequencing to obtain better coverage of low titer, divergent viruses. Applications include viral discovery from a complex background and improved sensitivity and coverage of rapidly evolving strains or variants in a gene family.",2014 Aug 3,"['Gardner, Shea N.', 'Jaing, Crystal J.', 'Elsheikh, Maher M.', 'Peña, José', 'Hysom, David A.', 'Borucki, Monica K.']",Adv Bioinformatics,,,True
de4137cea11509b6caf359fd5c66a215a1e8390f,PMC,Rapid Detection of Mycobacterium tuberculosis by Recombinase Polymerase Amplification,http://dx.doi.org/10.1371/journal.pone.0103091,PMC4138011,25118698,CC BY,"Improved access to effective tests for diagnosing tuberculosis (TB) has been designated a public health priority by the World Health Organisation. In high burden TB countries nucleic acid based TB tests have been restricted to centralised laboratories and specialised research settings. Requirements such as a constant electrical supply, air conditioning and skilled, computer literate operators prevent implementation of such tests in many settings. Isothermal DNA amplification technologies permit the use of simpler, less energy intensive detection platforms more suited to low resource settings that allow the accurate diagnosis of a disease within a short timeframe. Recombinase Polymerase Amplification (RPA) is a rapid, low temperature isothermal DNA amplification reaction. We report here RPA-based detection of Mycobacterium tuberculosis complex (MTC) DNA in <20 minutes at 39°C. Assays for two MTC specific targets were investigated, IS6110 and IS1081. When testing purified MTC genomic DNA, limits of detection of 6.25 fg (IS6110) and 20 fg (IS1081)were consistently achieved. When testing a convenience sample of pulmonary specimens from suspected TB patients, RPA demonstrated superior accuracy to indirect fluorescence microscopy. Compared to culture, sensitivities for the IS1081 RPA and microscopy were 91.4% (95%CI: 85, 97.9) and 86.1% (95%CI: 78.1, 94.1) respectively (n = 71). Specificities were 100% and 88.6% (95% CI: 80.8, 96.1) respectively. For the IS6110 RPA and microscopy sensitivities of 87.5% (95%CI: 81.7, 93.2) and 70.8% (95%CI: 62.9, 78.7) were obtained (n = 90). Specificities were 95.4 (95% CI: 92.3,98.1) and 88% (95% CI: 83.6, 92.4) respectively. The superior specificity of RPA for detecting tuberculosis was due to the reduced ability of fluorescence microscopy to distinguish Mtb complex from other acid fast bacteria. The rapid nature of the RPA assay and its low energy requirement compared to other amplification technologies suggest RPA-based TB assays could be of use for integration into a point-of-care test for use in resource constrained settings.",2014 Aug 13,"['Boyle, David S.', 'McNerney, Ruth', 'Teng Low, Hwee', 'Leader, Brandon Troy', 'Pérez-Osorio, Ailyn C.', 'Meyer, Jessica C.', ""O'Sullivan, Denise M."", 'Brooks, David G.', 'Piepenburg, Olaf', 'Forrest, Matthew S.']",PLoS One,,,True
5538bf904bcd32abf4ca1dbe9fc7e6c7514ebeda,PMC,A Quantitative Prioritisation of Human and Domestic Animal Pathogens in Europe,http://dx.doi.org/10.1371/journal.pone.0103529,PMC4138073,25136810,CC BY,"Disease or pathogen risk prioritisations aid understanding of infectious agent impact within surveillance or mitigation and biosecurity work, but take significant development. Previous work has shown the H-(Hirsch-)index as an alternative proxy. We present a weighted risk analysis describing infectious pathogen impact for human health (human pathogens) and well-being (domestic animal pathogens) using an objective, evidence-based, repeatable approach; the H-index. This study established the highest H-index European pathogens. Commonalities amongst pathogens not included in previous surveillance or risk analyses were examined. Differences between host types (humans/animals/zoonotic) in pathogen H-indices were explored as a One Health impact indicator. Finally, the acceptability of the H-index proxy for animal pathogen impact was examined by comparison with other measures. 57 pathogens appeared solely in the top 100 highest H-indices (1) human or (2) animal pathogens list, and 43 occurred in both. Of human pathogens, 66 were zoonotic and 67 were emerging, compared to 67 and 57 for animals. There were statistically significant differences between H-indices for host types (humans, animal, zoonotic), and there was limited evidence that H-indices are a reasonable proxy for animal pathogen impact. This work addresses measures outlined by the European Commission to strengthen climate change resilience and biosecurity for infectious diseases. The results include a quantitative evaluation of infectious pathogen impact, and suggest greater impacts of human-only compared to zoonotic pathogens or scientific under-representation of zoonoses. The outputs separate high and low impact pathogens, and should be combined with other risk assessment methods relying on expert opinion or qualitative data for priority setting, or could be used to prioritise diseases for which formal risk assessments are not possible because of data gaps.",2014 Aug 19,"['McIntyre, K. Marie', 'Setzkorn, Christian', 'Hepworth, Philip J.', 'Morand, Serge', 'Morse, Andrew P.', 'Baylis, Matthew']",PLoS One,,,True
2afa3da371e5495dd55f0b4dde4ae7700eaf99d6,PMC,"Rhinitis, Asthma and Respiratory Infections among Adults in Relation to the Home Environment in Multi-Family Buildings in Sweden",http://dx.doi.org/10.1371/journal.pone.0105125,PMC4138153,25136984,CC BY,"Risk factors for rhinitis, asthma and respiratory infections in the home environment were studied by a questionnaire survey. Totally 5775 occupants (≥18 years old) from a stratified random sample of multi-family buildings in Sweden participated (46%). 51.0% had rhinitis in the last 3 months (current rhinitis); 11.5% doctor diagnosed asthma; 46.4% respiratory infections in the last 3 months and 11.9% antibiotic medication for respiratory infections in the last 12 months. Associations between home environment and health were analyzed by multiple logistic regression, controlling for gender, age and smoking and mutual adjustment. Buildings constructed during 1960–1975 were risk factors for day time breathlessness (OR = 1.53, 95%CI 1.03–2.29). And those constructed during 1976–1985 had more current rhinitis (OR = 1.43, 95%CI 1.12–1.84) and respiratory infections (OR = 1.46, 95%CI 1.21–1.78). Cities with higher population density had more current rhinitis (p = 0.008) and respiratory infections (p<0.001). Rented apartments had more current rhinitis (OR = 1.23, 95%CI 1.07–1.40), wheeze (OR = 1.20, 95%CI 1.02–1.41), day time breathlessness (OR = 1.31, 95%CI 1.04–1.66) and respiratory infections (OR = 1.13, 95%CI 1.01–1.26). Living in colder parts of the country was a risk factor for wheeze (p = 0.03) and night time breathlessness (p = 0.002). Building dampness was a risk factor for wheeze (OR = 1.42, 95%CI 1.08–1.86) and day time breathlessness (OR = 1.57, 95%CI 1.09–2.27). Building dampness was a risk factor for health among those below 66 years old. Odor at home was a risk factor for doctor diagnosed asthma (OR = 1.49, 95%CI 1.08–2.06) and current asthma (OR = 1.52, 95%CI 1.03–2.24). Environmental tobacco smoke (ETS) was a risk factor for current asthma (OR = 1.53, 95%CI 1.09–2.16). Window pane condensation was a risk factor for antibiotic medication for respiratory infections (OR = 1.41, 95%CI 1.10–1.82). In conclusion, rhinitis, asthma and respiratory infections were related to a number of factors in the home environment. Certain building years (1961–1985), building dampness, window pane condensation and odor in the dwelling may be risk factors.",2014 Aug 19,"['Wang, Juan', 'Engvall, Karin', 'Smedje, Greta', 'Norbäck, Dan']",PLoS One,,,True
22d734ce865dda20bbbbd2695ffe67cb5bb10445,PMC,A canine model of experimental infection with Leishmania (L.) mexicana,http://dx.doi.org/10.1186/1756-3305-7-361,PMC4138396,25108307,CC BY,"BACKGROUND: Cutaneous leishmaniasis is a tropical disease affecting over one million patients annually and Leishmania (L.) mexicana is one of the major etiological agents in the Americas. Here we established the first experimental infection of L. (L.) mexicana in canids. METHODS: Beagle dogs were infected intradermally with culture-derived L. (L.) mexicana. We followed skin ulcer development, histopathological signs, parasite burden and the immune status of the infected dogs. RESULTS: All infected dogs developed uniform oval-craterform ulcers similar to those observed in humans, associated with mixed T helper 1/T helper 2 immune responses. Parasites were detected in the healed lesions 15 weeks post-infection. Higher anti-Leishmania IgG levels correlated with larger lesions and high IgG1/IgG2 ratio was associated with some level of splenomegaly. CONCLUSIONS: The canine model described in this work will be of use for further understanding of L. (L.) mexicana immunopathogenensis, and for drug and vaccine development.",2014 Aug 9,"['Cruz-Chan, Julio Vladimir', 'Carmen Aguilar-Cetina, Amarú del', 'Estefanía Villanueva-Lizama, Liliana', 'Pablo Martínez-Vega, Pedro', 'Jesús Ramírez-Sierra, Maria', 'Enrique Rosado-Vallado, Miguel', 'Leonardo Guillermo-Cordero, José', 'Dumonteil, Eric']",Parasit Vectors,,,True
c290f9617c78697d527d8a58bdbd8ef9af47fcfc,PMC,"Metagenomic Survey for Viruses in Western Arctic Caribou, Alaska, through Iterative Assembly of Taxonomic Units",http://dx.doi.org/10.1371/journal.pone.0105227,PMC4139337,25140520,CC0,"Pathogen surveillance in animals does not provide a sufficient level of vigilance because it is generally confined to surveillance of pathogens with known economic impact in domestic animals and practically nonexistent in wildlife species. As most (re-)emerging viral infections originate from animal sources, it is important to obtain insight into viral pathogens present in the wildlife reservoir from a public health perspective. When monitoring living, free-ranging wildlife for viruses, sample collection can be challenging and availability of nucleic acids isolated from samples is often limited. The development of viral metagenomics platforms allows a more comprehensive inventory of viruses present in wildlife. We report a metagenomic viral survey of the Western Arctic herd of barren ground caribou (Rangifer tarandus granti) in Alaska, USA. The presence of mammalian viruses in eye and nose swabs of 39 free-ranging caribou was investigated by random amplification combined with a metagenomic analysis approach that applied exhaustive iterative assembly of sequencing results to define taxonomic units of each metagenome. Through homology search methods we identified the presence of several mammalian viruses, including different papillomaviruses, a novel parvovirus, polyomavirus, and a virus that potentially represents a member of a novel genus in the family Coronaviridae.",2014 Aug 20,"['Schürch, Anita C.', 'Schipper, Debby', 'Bijl, Maarten A.', 'Dau, Jim', 'Beckmen, Kimberlee B.', 'Schapendonk, Claudia M. E.', 'Raj, V. Stalin', 'Osterhaus, Albert D. M. E.', 'Haagmans, Bart L.', 'Tryland, Morten', 'Smits, Saskia L.']",PLoS One,,,True
d1913c3e3106846c33b96d7276edc1d2a62b1a1e,PMC,Serum Diamine Oxidase as a Hemorrhagic Shock Biomarker in a Rabbit Model,http://dx.doi.org/10.1371/journal.pone.0102285,PMC4140717,25144315,CC BY,"BACKGROUND: In prolonged hemorrhagic shock, reductions in intestinal mucosal blood perfusion lead to mucosal barrier damage and systemic inflammation. Gastrointestinal failure in critically ill patients has a poor prognosis, so early assessment of mucosal barrier injury in shock patients is clinically relevant. Unfortunately, there is no serum marker that can accurately assess intestinal ischemia-reperfusion injury. OBJECTIVE: The aim of this study was to assess if serum diamine oxidase levels can reflect intestinal mucosal injury subsequent to prolonged hemorrhagic shock. METHODS: Thirty New Zealand white rabbits were divided into three groups: a control group, a medium blood pressure (BP) group (exsanguinated to a shock BP of 50 to 41 mm Hg), and a low BP group (exsanguinated to a shock blood pressure of 40 to 31 mm Hg), in which the shock BP was sustained for 180 min prior to fluid resuscitation. RESULTS: The severity of hemorrhagic shock in the low BP group was significantly greater than that of the medium BP group according to the post-resuscitation BP, serum tumor necrosis factor (TNF)-α, and arterial lactate. Intestinal damage was significantly more severe in the low BP group according to Chiu’s scoring, claudin-1, intercellular adhesion molecule (ICAM)-1, and myeloperoxidase expression. Serum diamine oxidase was significantly increased in the low BP group compared to the medium BP and control groups and was negatively correlated with shock BP. CONCLUSION: Serum diamine oxidase can be used as a serological marker in evaluating intestinal injury and shows promise as an indicator of hemorrhagic shock severity.",2014 Aug 21,"['Zhao, Liang', 'Luo, Lin', 'Jia, Weikun', 'Xiao, Juan', 'Huang, Gang', 'Tian, Geng', 'Li, Jingwei', 'Xiao, Yingbin']",PLoS One,,,True
4d392425fe3005f145fdfa835421ff0aa5fe0104,PMC,Early-Life Hepatitis E Infection in Pigs: The Importance of Maternally-Derived Antibodies,http://dx.doi.org/10.1371/journal.pone.0105527,PMC4140806,25144763,CC BY,"Passive immunity (PI), acquired through colostrum intake, is essential for piglet protection against pathogens. Maternally-derived antibodies (MDAs) can decrease the transmission of pathogens between individuals by reducing shedding from infected animals and/or susceptibility of naïve animals. Only a limited number of studies, however, have been carried out to quantify the level of protection conferred by PI in terms of transmission. In the present study, an original modeling framework was designed to estimate parameters governing the transmission of infectious agents in the presence and absence of PI. This epidemiological model accounts for the distribution of PI duration and two different forces of infection depending on the serological status of animals after colostrum intake. A Bayesian approach (Metropolis-Hastings algorithm) was used for parameter estimation. The impact of PI on hepatitis E virus transmission in piglets was investigated using longitudinal serological data from six pig farms. A strong impact of PI was highlighted, the efficiency of transmission being on average 13 times lower in piglets with maternally-derived antibodies than in fully susceptible animals (range: 5–21). Median infection-free survival ages, based on herd-specific estimates, ranged between 8.7 and 13.8 weeks in all but one herd. Indeed, this herd exhibited a different profile with a relatively low prevalence of infected pigs (50% at slaughter age) despite the similar proportions of passively immune individuals after colostrum intake. These results suggest that the age at HEV infection is not strictly dependent upon the proportion of piglets with PI but is also linked to farm-specific husbandry (mingling of piglets after weaning) and hygiene practices. The original methodology developed here, using population-based longitudinal serological data, was able to demonstrate the relative impact of MDAs on the transmission of infectious agents.",2014 Aug 21,"['Andraud, Mathieu', 'Casas, Maribel', 'Pavio, Nicole', 'Rose, Nicolas']",PLoS One,,,True
78f939545e7217684295ab63900119ab1ebdb173,PMC,Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset,http://dx.doi.org/10.1371/journal.ppat.1004250,PMC4140844,25144235,CC0,"The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia leading to euthanasia of some animals. Extensive lesions were evident in the lungs of all animals necropsied at different time points post inoculation. Some animals were also viremic; high viral loads were detected in the lungs of all infected animals, and total RNAseq demonstrated the induction of immune and inflammatory pathways. This is the first description of a severe, partially lethal, disease model of MERS-CoV, and as such will have a major impact on the ability to assess the efficacy of vaccines and treatment strategies as well as allowing more detailed pathogenesis studies.",2014 Aug 21,"['Falzarano, Darryl', 'de Wit, Emmie', 'Feldmann, Friederike', 'Rasmussen, Angela L.', 'Okumura, Atsushi', 'Peng, Xinxia', 'Thomas, Matthew J.', 'van Doremalen, Neeltje', 'Haddock, Elaine', 'Nagy, Lee', 'LaCasse, Rachel', 'Liu, Tingting', 'Zhu, Jiang', 'McLellan, Jason S.', 'Scott, Dana P.', 'Katze, Michael G.', 'Feldmann, Heinz', 'Munster, Vincent J.']",PLoS Pathog,,,True
e840685d875ae1d0d6c08a0176f2151b2765a0d0,PMC,"Proteomics analysis reveals protein expression differences for hypopharyngeal gland activity in the honeybee, Apis mellifera carnica Pollmann",http://dx.doi.org/10.1186/1471-2164-15-665,PMC4141115,25103401,CC BY,"BACKGROUND: Most of the proteins contained in royal jelly (RJ) are secreted from the hypopharyngeal glands (HG) of young bees. Although generic protein composition of RJ has been investigated, little is known about how age-dependent changes on HG secretion affect RJ composition and their biological consequences. In this study, we identified differentially expressed proteins (DEPs) during HG development by using the isobaric tag for relative and absolute quantification (iTRAQ) labeling technique. This proteomic method increases the potential for new protein discovery by improving the identification of low quantity proteins. RESULTS: A total of 1282 proteins were identified from five age groups of worker bees, 284 of which were differentially expressed. 43 (15.1%) of the DEPs were identified for the first time. Comparison of samples at day 6, 9, 12, and 16 of development relative to day 3 led to the unambiguous identification of 112, 117, 127, and 127 DEPs, respectively. The majority of these DEPs were up-regulated in the older worker groups, indicating a substantial change in the pattern of proteins expressed after 3 days. DEPs were identified among all the age groups, suggesting that changes in protein expression during HG ontogeny are concomitant with different states of worker development. A total of 649 proteins were mapped to canonical signaling pathways found in the Kyoto Encyclopedia of Genes and Genomes (KEGG), which were preferentially associated with metabolism and biosynthesis of secondary metabolites. More than 10 key high-abundance proteins were involved in signaling pathways related to ribosome function and protein processing in the endoplasmic reticulum. The results were validated by qPCR. CONCLUSION: Our approach demonstrates that HG experienced important changes in protein expression during its ontogenic development, which supports the secretion of proteins involved in diverse functions in adult workers beyond its traditional role in royal jelly production. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-665) contains supplementary material, which is available to authorized users.",2014 Aug 8,"['Ji, Ting', 'Liu, Zhenguo', 'Shen, Jie', 'Shen, Fang', 'Liang, Qin', 'Wu, Liming', 'Chen, Guohong', 'Corona, Miguel']",BMC Genomics,,,True
9235d0eee63bf8da637b7b63b983d58d2372f0d3,PMC,Genetic Variants of CD209 Associated with Kawasaki Disease Susceptibility,http://dx.doi.org/10.1371/journal.pone.0105236,PMC4141786,25148534,CC BY,"BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis with unknown etiology mainly affecting children in Asian countries. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN, CD209) in humans was showed to trigger an anti-inflammatory cascade and associated with KD susceptibility. This study was conducted to investigate the association between genetic polymorphisms of CD209 and the risk KD. METHODS: A total of 948 subjects (381 KD and 567 controls) were recruited. Nine tagging SNPs (rs8112310, rs4804800, rs11465421, rs1544766, rs4804801, rs2287886, rs735239, rs735240, rs4804804) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis. RESULTS: Significant associations were found between CD209 polymorphisms (rs4804800, rs2287886, rs735240) and the risk of KD. Haplotype analysis for CD209 polymorphisms showed that A/A/G haplotype (P = 0.0002, OR = 1.61) and G/A/G haplotype (P = 0.0365, OR = 1.52) had higher risk of KD as compared with G/G/A haplotype in rs2287886/rs735239/rs735240 pairwise allele analysis. There were no significant association in KD with regards to CAL formation and IVIG treatment responses. CONCLUSION: CD209 polymorphisms were responsible for the susceptibility of KD, but not CAL formation and IVIG treatment responsiveness.",2014 Aug 22,"['Kuo, Ho-Chang', 'Huang, Ying-Hsien', 'Chien, Shu-Chen', 'Yu, Hong-Ren', 'Hsieh, Kai-Sheng', 'Hsu, Yu-Wen', 'Chang, Wei-Chiao']",PLoS One,,,True
5a85b1a03f6d5cebc70bad6027c941a2224f0df0,PMC,"Genomic Characterization of a Circovirus Associated with Fatal Hemorrhagic Enteritis in Dog, Italy",http://dx.doi.org/10.1371/journal.pone.0105909,PMC4141843,25147946,CC BY,"Dog circovirus (DogCV) was identified in an outbreak of enteritis in pups in Italy. The disease was observed in 6 young dachshunds pups of a litter from a breeding kennel and caused the death of 2 dogs. Upon full-genome analysis, the virus detected in one of the dead pups (strain Bari/411–13) was closely related to DogCVs that have been recently isolated in the USA. The present study, if corroborated by further reports, could represent a useful contribution to the knowledge of the pathogenic potential of DogCV and its association with enteritis in dogs.",2014 Aug 22,"['Decaro, Nicola', 'Martella, Vito', 'Desario, Costantina', 'Lanave, Gianvito', 'Circella, Elena', 'Cavalli, Alessandra', 'Elia, Gabriella', 'Camero, Michele', 'Buonavoglia, Canio']",PLoS One,,,True
8c43b5c8a56828ee5687a2b572dc05333c2815a0,PMC,Highlights from the 2014 International Symposium on HIV & Emerging Infectious Diseases (ISHEID): from cART management to the end of the HIV pandemic,http://dx.doi.org/10.1186/1742-6405-11-28,PMC4145833,25165483,CC BY,"The 2014 International Symposium on HIV and Emerging Infectious Diseases (ISHEID) provided a forum for investigators to hear the latest research developments in the clinical management of HIV and HCV infections as well as HIV cure research. Combined anti-retroviral therapy (c-ART) has had a profound impact on the disease prognosis and transformed this infection into a chronic disease. However, HIV is able to persist within the infected host and the pandemic is still growing. The main 2014 ISHEID theme was, hence “Together for a world without HIV and AIDS”. In this report we not only give details on this main topic but also summarize what has been discussed in the areas of HCV coinfection and present a short summary on currently emerging viral diseases.",2014 Aug 21,"['Lafeuillade, Alain', 'Wainberg, Mark', 'Gougeon, Marie-Lise', 'Loes, Sabine Kinloch-de', 'Halfon, Philippe', 'Tissot-Dupont, Hervé']",AIDS Res Ther,,,True
a62bab2887ddd15979d7ef71e48ea7ae3596adf6,PMC,"The Antibody Germline/Maturation Hypothesis, Elicitation of Broadly Neutralizing Antibodies Against HIV-1 and Cord Blood IgM Repertoires",http://dx.doi.org/10.3389/fimmu.2014.00398,PMC4147355,25221552,CC BY,"We have previously observed that all known potent broadly neutralizing antibodies (bnAbs) against HIV-1 are highly divergent from their putative germline predecessors in contrast to bnAbs against viruses causing acute infections such as henipaviruses and SARS CoV, which are much less divergent from their germline counterparts. Consequently, we have hypothesized that germline antibodies may not bind to the HIV-1 envelope glycoprotein (Env) because they are so different compared to the highly somatically mutated HIV-1-specific bnAbs. We have further hypothesized that the immunogenicity of highly conserved epitopes on the HIV-1 envelope glycoproteins (Envs) may be reduced or eliminated by their very weak or absent interactions with germline antibodies and immune responses leading to the elicitation of bnAbs may not be initiated and/or sustained. Even if such responses are initiated, the maturation pathways are so extraordinarily complex that prolonged periods of time may be required for elicitation of bnAbs with defined unique sequences. We provided the initial evidence supporting this antibody germline/maturation hypothesis, which prompted a number of studies to design vaccine immunogens that could bind putative germline predecessors of known bnAbs and to explore complex B cell lineages. However, guiding the immune system through the exceptionally complex antibody maturation pathways to elicit known bnAbs remains a major challenge. Here, we discuss studies exploring the antibody germline/maturation hypothesis as related to elicitation of bnAbs against HIV-1 and present our recent data demonstrating the existence of germline-like precursors of VRC01 antibodies in a human cord blood IgM library.",2014 Aug 28,"['Prabakaran, Ponraj', 'Chen, Weizao', 'Dimitrov, Dimiter S.']",Front Immunol,,,True
52f1664a1d9fae42e3fbc1f19d936c711826a931,PMC,Identification of Cis-Acting Elements on Positive-Strand Subgenomic mRNA Required for the Synthesis of Negative-Strand Counterpart in Bovine Coronavirus,http://dx.doi.org/10.3390/v6082938,PMC4147681,25080125,CC BY,"It has been demonstrated that, in addition to genomic RNA, sgmRNA is able to serve as a template for the synthesis of the negative-strand [(−)-strand] complement. However, the cis-acting elements on the positive-strand [(+)-strand] sgmRNA required for (−)-strand sgmRNA synthesis have not yet been systematically identified. In this study, we employed real-time quantitative reverse transcription polymerase chain reaction to analyze the cis-acting elements on bovine coronavirus (BCoV) sgmRNA 7 required for the synthesis of its (−)-strand counterpart by deletion mutagenesis. The major findings are as follows. (1) Deletion of the 5'-terminal leader sequence on sgmRNA 7 decreased the synthesis of the (−)-strand sgmRNA complement. (2) Deletions of the 3' untranslated region (UTR) bulged stem-loop showed no effect on (−)-strand sgmRNA synthesis; however, deletion of the 3' UTR pseudoknot decreased the yield of (−)-strand sgmRNA. (3) Nucleotides positioned from −15 to −34 of the sgmRNA 7 3'-terminal region are required for efficient (−)-strand sgmRNA synthesis. (4) Nucleotide species at the 3'-most position (−1) of sgmRNA 7 is correlated to the efficiency of (−)-strand sgmRNA synthesis. These results together suggest, in principle, that the 5'- and 3'-terminal sequences on sgmRNA 7 harbor cis-acting elements are critical for efficient (−)-strand sgmRNA synthesis in BCoV.",2014 Jul 30,"['Yeh, Po-Yuan', 'Wu, Hung-Yi']",Viruses,,,True
bc070e8139c6a9087e25333319f8b852aee81836,PMC,Identification of Cis-Acting Elements on Positive-Strand Subgenomic mRNA Required for the Synthesis of Negative-Strand Counterpart in Bovine Coronavirus,http://dx.doi.org/10.3390/v6082938,PMC4147681,25080125,CC BY,"It has been demonstrated that, in addition to genomic RNA, sgmRNA is able to serve as a template for the synthesis of the negative-strand [(−)-strand] complement. However, the cis-acting elements on the positive-strand [(+)-strand] sgmRNA required for (−)-strand sgmRNA synthesis have not yet been systematically identified. In this study, we employed real-time quantitative reverse transcription polymerase chain reaction to analyze the cis-acting elements on bovine coronavirus (BCoV) sgmRNA 7 required for the synthesis of its (−)-strand counterpart by deletion mutagenesis. The major findings are as follows. (1) Deletion of the 5'-terminal leader sequence on sgmRNA 7 decreased the synthesis of the (−)-strand sgmRNA complement. (2) Deletions of the 3' untranslated region (UTR) bulged stem-loop showed no effect on (−)-strand sgmRNA synthesis; however, deletion of the 3' UTR pseudoknot decreased the yield of (−)-strand sgmRNA. (3) Nucleotides positioned from −15 to −34 of the sgmRNA 7 3'-terminal region are required for efficient (−)-strand sgmRNA synthesis. (4) Nucleotide species at the 3'-most position (−1) of sgmRNA 7 is correlated to the efficiency of (−)-strand sgmRNA synthesis. These results together suggest, in principle, that the 5'- and 3'-terminal sequences on sgmRNA 7 harbor cis-acting elements are critical for efficient (−)-strand sgmRNA synthesis in BCoV.",2014 Jul 30,"['Yeh, Po-Yuan', 'Wu, Hung-Yi']",Viruses,,,False
b190452f13e95ef0af0c07243e44a98371fe00eb,PMC,The Coronavirus Nucleocapsid Is a Multifunctional Protein,http://dx.doi.org/10.3390/v6082991,PMC4147684,25105276,CC BY,"The coronavirus nucleocapsid (N) is a structural protein that forms complexes with genomic RNA, interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. Recent studies have confirmed that N is a multifunctional protein. The aim of this review is to highlight the properties and functions of the N protein, with specific reference to (i) the topology; (ii) the intracellular localization and (iii) the functions of the protein.",2014 Aug 7,"['McBride, Ruth', 'van Zyl, Marjorie', 'Fielding, Burtram C.']",Viruses,,,True
f6d2afb2ec44d8656972ea79f8a833143bbeb42b,PMC,Virus-Vectored Influenza Virus Vaccines,http://dx.doi.org/10.3390/v6083055,PMC4147686,25105278,CC BY,"Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines.",2014 Aug 7,"['Tripp, Ralph A.', 'Tompkins, S. Mark']",Viruses,,,True
f87ca9ce6ad3323737c273a36a56a08d050b2d26,PMC,European Bats as Carriers of Viruses with Zoonotic Potential,http://dx.doi.org/10.3390/v6083110,PMC4147689,25123684,CC BY,"Bats are being increasingly recognized as reservoir hosts of highly pathogenic and zoonotic emerging viruses (Marburg virus, Nipah virus, Hendra virus, Rabies virus, and coronaviruses). While numerous studies have focused on the mentioned highly human-pathogenic bat viruses in tropical regions, little is known on similar human-pathogenic viruses that may be present in European bats. Although novel viruses are being detected, their zoonotic potential remains unclear unless further studies are conducted. At present, it is assumed that the risk posed by bats to the general public is rather low. In this review, selected viruses detected and isolated in Europe are discussed from our point of view in regard to their human-pathogenic potential. All European bat species and their roosts are legally protected and some European species are even endangered. Nevertheless, the increasing public fear of bats and their viruses is an obstacle to their protection. Educating the public regarding bat lyssaviruses might result in reduced threats to both the public and the bats.",2014 Aug 13,"['Kohl, Claudia', 'Kurth, Andreas']",Viruses,,,True
b95e82e0343a470f5b39c97eae9f8541e218b76d,PMC,Canine Enteric Coronaviruses: Emerging Viral Pathogens with Distinct Recombinant Spike Proteins,http://dx.doi.org/10.3390/v6083363,PMC4147700,25153347,CC BY,"Canine enteric coronavirus (CCoV) is an alphacoronavirus infecting dogs that is closely related to enteric coronaviruses of cats and pigs. While CCoV has traditionally caused mild gastro-intestinal clinical signs, there are increasing reports of lethal CCoV infections in dogs, with evidence of both gastrointestinal and systemic viral dissemination. Consequently, CCoV is now considered to be an emerging infectious disease of dogs. In addition to the two known serotypes of CCoV, novel recombinant variants of CCoV have been found containing spike protein N-terminal domains (NTDs) that are closely related to those of feline and porcine strains. The increase in disease severity in dogs and the emergence of novel CCoVs can be attributed to the high level of recombination within the spike gene that can occur during infection by more than one CCoV type in the same host.",2014 Aug 22,"['Licitra, Beth N.', 'Duhamel, Gerald E.', 'Whittaker, Gary R.']",Viruses,,,True
b147a9e7654ef4257a7c45cae6606543a7864c80,PMC,FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination,http://dx.doi.org/10.1186/s12974-014-0138-y,PMC4148542,25138356,CC BY,"BACKGROUND: FTY720 (fingolimod) is the first oral drug approved by the Food and Drug Administration for treatment of patients with the relapsing-remitting form of the human demyelinating disease multiple sclerosis. Evidence suggests that the therapeutic benefit of FTY720 occurs by preventing the egress of lymphocytes from lymph nodes thereby inhibiting the infiltration of disease-causing lymphocytes into the central nervous system (CNS). We hypothesized that FTY720 treatment would affect lymphocyte migration to the CNS and influence disease severity in a mouse model of viral-induced neurologic disease. METHODS: Mice were infected intracranially with the neurotropic JHM strain of mouse hepatitis virus. Infected animals were treated with increasing doses (1, 3 and 10 mg/kg) of FTY720 and morbidity and mortality recorded. Infiltration of inflammatory virus-specific T cells (tetramer staining) into the CNS of FTY720-treated mice was determined using flow cytometry. The effects of FTY720 treatment on virus-specific T cell proliferation, cytokine production and cytolytic activity were also determined. The severity of neuroinflammation and demyelination in FTY720-treated mice was examined by flow cytometry and histopathologically, respectively, in the spinal cords of the mice. RESULTS: Administration of FTY720 to JHMV-infected mice resulted in increased clinical disease severity and mortality. These results correlated with impaired ability to control viral replication (P < 0.05) within the CNS at days 7 and 14 post-infection, which was associated with diminished accumulation of virus-specific CD4+ and CD8+ T cells (P < 0.05) into the CNS. Reduced neuroinflammation in FTY720-treated mice correlated with increased retention of T lymphocytes within draining cervical lymph nodes (P < 0.05). Treatment with FTY720 did not affect virus-specific T cell proliferation, expression of IFN-γ, TNF-α or cytolytic activity. FTY720-treated mice exhibited a reduction in the severity of demyelination associated with dampened neuroinflammation. CONCLUSION: These findings indicate that FTY720 mutes effective anti-viral immune responses through impacting migration and accumulation of virus-specific T cells within the CNS during acute viral-induced encephalomyelitis. FTY720 treatment reduces the severity of neuroinflammatory-mediated demyelination by restricting the access of disease-causing lymphocytes into the CNS but is not associated with viral recrudescence in this model.",2014 Aug 20,"['Blanc, Caroline A', 'Rosen, Hugh', 'Lane, Thomas E']",J Neuroinflammation,,,True
8705d3a93c346b8b21e349c6263e680d844e7aea,PMC,NK Cells in Mucosal Defense against Infection,http://dx.doi.org/10.1155/2014/413982,PMC4150440,25197644,CC BY,"Conventional natural killer cells (NK cells) provide continual surveillance for cancer and rapid responses to infection. They develop in the bone marrow, emerge as either NK precursor cells, immature, or mature cells, and disperse throughout the body. In the periphery NK cells provide critical defense against pathogens and cancer and are noted to develop features of adaptive immune responses. In the tightly regulated and dynamic mucosal tissues, they set up residency via unknown mechanisms and from sources that are yet to be defined. Once resident, they appear to have the ability to functionally mature dependent on the mucosal tissue microenvironment. Mucosal NK cells play a pivotal role in early protection through their cytolytic function and IFNγ production against bacteria, fungi, viruses, and parasitic infections. This review presents what is known about NK cell development and phenotypes of mucosal tissue resident conventional NK cells. The question of how they come to reside in their tissues and published data on their function against pathogens during mucosal infection are discussed. Dissecting major questions highlighted in this review will be important to the further understanding of NK cell homing and functional diversity and improve rational design of NK cell based therapies against mucosal infection.",2014 Aug 14,"['Ivanova, Daria', 'Krempels, Ryan', 'Ryfe, Jennyfer', 'Weitzman, Kaitlyn', 'Stephenson, David', 'Gigley, Jason P.']",Biomed Res Int,,,True
4b138ca6c96ce56fb2db1641847bd7686ca1cdff,PMC,Western Cold and Flu (WeCoF) aerosol study – preliminary results,http://dx.doi.org/10.1186/1756-0500-7-563,PMC4150972,25148847,CC BY,"BACKGROUND: Influenza virus is responsible for annual deaths due to seasonal epidemics and is the cause of major pandemics which have claimed millions of human lives over the last century. Knowledge about respiratory virus transmission is advancing. Spread is likely through the air, but much work remains to be done to characterize the aerosols produced by infected individuals, including viral particle survival and infectivity. Although coughs have been characterized, little work has been done to examine coughs from infected individuals. The WeCoF project aims at providing evidence to support prevention measures to mitigate person-to-person influenza transmission in critical locations, such as hospitals, and during pandemics. FINDINGS: A novel experimental cough chamber facility – the FLUGIE – has been developed to study the far-field aerodynamics and aerosol transport of droplets produced by the coughs from humans naturally-infected with influenza. The flow field of each cough is measured using Particle Image Velocimetry (PIV). A preliminary study involving 12 healthy individuals has been carried out in order to quantify the strengths of their coughs at a distance of 1 m from the mouth. The spatially averaged maximum velocity was determined and the average value was 0.41 m/s across 27 coughs of good data quality. The peak value of velocity was also extracted and compared with the average velocity. CONCLUSIONS: Preliminary results show that there is significant air motion associated with a cough (on the order of 0.5 m/s) as far away as 1 m from the mouth of the healthy person who coughs. The results from this pilot study provide the framework for a more extensive participant recruitment campaign that will encompass a statistically-significant cohort.",2014 Aug 23,"['Savory, Eric', 'Lin, William E', 'Blackman, Karin', 'Roberto, Matthew C', 'Cuthbertson, Lauren R', 'Scott, James A', 'Mubareka, Samira']",BMC Res Notes,,,True
9f548a03c496ef67ce743572cca4201debbf9910,PMC,Ethics of Clinical Science in a Public Health Emergency: Drug Discovery at the Bedside,http://dx.doi.org/10.1080/15265161.2013.813597,PMC4151792,23952822,CC BY,"Clinical research under the usual regulatory constraints may be difficult or even impossible in a public health emergency. Regulators must seek to strike a good balance in granting as wide therapeutic access to new drugs as possible at the same time as gathering sound evidence of safety and effectiveness. To inform current policy, I reexamine the philosophical rationale for restricting new medicines to clinical trials, at any stage and for any population of patients (which resides in the precautionary principle), to show that its objective to protect public health, now or in the future, could soon be defeated in a pandemic. Providing wider therapeutic access and coordinating observations and natural experiments, including service delivery by cluster (wedged cluster trials), may provide such a balance. However, there are important questions of fairness to resolve before any such research can proceed.",2013 Sep 1,"Edwards, Sarah J. L.",Am J Bioeth,,,True
6d08d5d8add16122735dcfa90a4c36f8d2a348ea,PMC,Defensins and Sepsis,http://dx.doi.org/10.1155/2014/180109,PMC4151856,25210703,CC BY,"Sepsis is a leading cause of mortality and morbidity in the critical illness. Multiple immune inflammatory processes take part in the pathogenesis of sepsis. Defensins are endogenous antimicrobial peptides with three disulphide bonds created by six cysteine residues. Besides the intrinsic microbicidal properties, defensins are active players which modulate both innate and adaptive immunity against various infections. Defensins can recruit neutrophils, enhance phagocytosis, chemoattract T cells and dendritic cells, promote complement activation, and induce IL-1β production and pyrotosis. Previous publications have documented that defensins play important roles in a series of immune inflammatory diseases including sepsis. This review aims to briefly summarize in vitro, in vivo, and genetic studies on defensins' effects as well as corresponding mechanisms within sepsis and highlights their promising findings which may be potential targets in future therapies of sepsis.",2014 Aug 19,"['Xie, Guo-Hao', 'Chen, Qi-Xing', 'Cheng, Bao-Li', 'Fang, Xiang-Ming']",Biomed Res Int,,,True
19b9ee3dcd89f01eea3e48b333888b1ce70b296f,PMC,Emergence of Pathogenic Coronaviruses in Cats by Homologous Recombination between Feline and Canine Coronaviruses,http://dx.doi.org/10.1371/journal.pone.0106534,PMC4152292,25180686,CC BY,"Type II feline coronavirus (FCoV) emerged via double recombination between type I FCoV and type II canine coronavirus (CCoV). In this study, two type I FCoVs, three type II FCoVs and ten type II CCoVs were genetically compared. The results showed that three Japanese type II FCoVs, M91-267, KUK-H/L and Tokyo/cat/130627, also emerged by homologous recombination between type I FCoV and type II CCoV and their parent viruses were genetically different from one another. In addition, the 3′-terminal recombination sites of M91-267, KUK-H/L and Tokyo/cat/130627 were different from one another within the genes encoding membrane and spike proteins, and the 5′-terminal recombination sites were also located at different regions of ORF1. These results indicate that at least three Japanese type II FCoVs emerged independently. Sera from a cat experimentally infected with type I FCoV was unable to neutralize type II CCoV infection, indicating that cats persistently infected with type I FCoV may be superinfected with type II CCoV. Our previous study reported that few Japanese cats have antibody against type II FCoV. All of these observations suggest that type II FCoV emerged inside the cat body and is unable to readily spread among cats, indicating that these recombination events for emergence of pathogenic coronaviruses occur frequently.",2014 Sep 2,"['Terada, Yutaka', 'Matsui, Nobutaka', 'Noguchi, Keita', 'Kuwata, Ryusei', 'Shimoda, Hiroshi', 'Soma, Takehisa', 'Mochizuki, Masami', 'Maeda, Ken']",PLoS One,,,True
2fadcd6b5c3ddc519094af150095be7578d8499b,PMC,Topology and biological function of enterovirus non-structural protein 2B as a member of the viroporin family,http://dx.doi.org/10.1186/s13567-014-0087-6,PMC4155101,25163654,CC BY,"Viroporins are a group of transmembrane proteins with low molecular weight that are encoded by many animal viruses. Generally, viroporins are composed of 50–120 amino acid residues and possess a minimum of one hydrophobic region that interacts with the lipid bilayer and leads to dispersion. Viroporins are involved in destroying the morphology of host cells and disturbing their biological functions to complete the life cycle of the virus. The 2B proteins encoded by enteroviruses, which belong to the family Picornaviridae, can form transmembrane pores by oligomerization, increase the permeability of plasma membranes, disturb the homeostasis of calcium in cells, induce apoptosis, and cause autophagy; these abilities are shared among viroporins. The present paper introduces the structure and biological characteristics of various 2B proteins encoded by enteroviruses of the family Picornaviridae and may provide a novel idea for developing antiviral drugs.",2014 Aug 28,"['Ao, Da', 'Sun, Shi-Qi', 'Guo, Hui-Chen']",Vet Res,,,True
34ccc1c615fa5697b5926c7ce5f1ea21bc06f5fa,PMC,Spherules and IBV,http://dx.doi.org/10.4161/bioe.29323,PMC4156489,25482229,CC BY,"Infectious bronchitis virus (IBV) is an economically important virus infecting chickens, causing large losses to the poultry industry globally. While vaccines are available, there is a requirement for novel vaccine strategies due to high strain variation and poor cross-protection. This requires a more detailed understanding of virus-host cell interactions to identify candidates for targeted virus attenuation. One key area of research in the positive sense RNA virus field, due to its central role in virus replication, is the induction of cellular membrane rearrangements by this class of viruses for the assembly of virus replication complexes. In our recent work, we identified the structures induced by IBV during infection of cultured cells, as well as primary cells and ex vivo organ culture. We identified structures novel to the coronavirus family, which strongly resemble replication sites of other positive sense RNA viruses. We have begun to extend this work using recombinant IBVs, which are chimera of different virus strains to study the role of viral proteins in the induction of membrane rearrangements.",2014 Sep 1,"['Maier, Helena J', 'Hawes, Philippa C', 'Keep, Sarah M', 'Britton, Paul']",Bioengineered,,,True
94ba61be5805b1b0caef6716c00ed234be78b021,PMC,The Role of Myeloid Cell Activation and Arginine Metabolism in the Pathogenesis of Virus-Induced Diseases,http://dx.doi.org/10.3389/fimmu.2014.00428,PMC4157561,25250029,CC BY,"When an antiviral immune response is generated, a balance must be reached between two opposing pathways: the production of proinflammatory and cytotoxic effectors that drive a robust antiviral immune response to control the infection and regulators that function to limit or blunt an excessive immune response to minimize immune-mediated pathology and repair tissue damage. Myeloid cells, including monocytes and macrophages, play an important role in this balance, particularly through the activities of the arginine-hydrolyzing enzymes nitric oxide synthase 2 (Nos2; iNOS) and arginase 1 (Arg1). Nitric oxide (NO) production by iNOS is an important proinflammatory mediator, whereas Arg1-expressing macrophages contribute to the resolution of inflammation and wound repair. In the context of viral infections, expression of these enzymes can result in a variety of outcomes for the host. NO has direct antiviral properties against some viruses, whereas during other virus infections NO can mediate immunopathology and/or inhibit the antiviral immune response to promote chronic infection. Arg1 activity not only has important wound healing functions but can also inhibit the antiviral immune response during some viral infections. Thus, depending on the specific virus and the tissue(s) involved, the activity of both of these arginine-hydrolyzing enzymes can either exacerbate or limit the severity of virus-induced disease. In this review, we will discuss a variety of viral infections, including HIV, SARS-CoV, LCMV, HCV, RSV, and others, where myeloid cells influence the control and clearance of the virus from the host, as well as the severity and resolution of tissue damage, via the activities of iNOS and/or Arg1. Clearly, monocyte/macrophage activation and arginine metabolism will continue to be important areas of investigation in the context of viral infections.",2014 Sep 8,"['Burrack, Kristina S.', 'Morrison, Thomas E.']",Front Immunol,,,True
e49106784cd05d905c10780cc5dbe2a10a6badb7,PMC,Correction: Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset,http://dx.doi.org/10.1371/journal.ppat.1004431,PMC4159343,,CC BY,,2014 Sep 9,,PLoS Pathog,,,True
8b369168263656b024f65707b9bb501d1b75a56e,PMC,Heterogeneous pathological outcomes after experimental pH1N1 influenza infection in ferrets correlate with viral replication and host immune responses in the lung,http://dx.doi.org/10.1186/s13567-014-0085-8,PMC4161856,25163545,CC BY,"The swine-origin pandemic (p) H1N1 influenza A virus causes mild upper-respiratory tract disease in most human patients. However, some patients developed severe lower-respiratory tract infections with fatal consequences, and the cause of these infections remain unknown. Recently, it has been suggested that different populations have different degrees of susceptibility to pH1N1 strains due to host genetic variations that are associated with inappropriate immune responses against viral genetic characteristics. Here, we tested whether the pathologic patterns of influenza strains that produce different disease outcomes in humans could be reproduced in a ferret model. Our results revealed that the severities of infection did not correspond to particular viral isolate and were not associated with the clinical phenotypes of the corresponding patients. Severe pathological outcomes were associated with higher viral replication, especially in alveolar areas, and with an exacerbated innate cellular immune response that was characterised by substantial phagocytic and cytotoxic cell migration into the lungs. Moreover, detrimental innate cellular responses were linked to the up-regulation of several proinflammatory cytokines and chemokines and the down-regulation of IFNα in the lungs. Additionally, severe lung lesions were associated with greater up-regulations of pro-apoptotic markers and higher levels of apoptotic neutrophils and macrophages. In conclusion, this study confirmed that the clinicopathological outcomes of pH1N1 infection in ferrets were not only due to viral replication abilities but also depended on the hosts’ capacities to mount efficient immune responses to control viral infection of the lung. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-014-0085-8) contains supplementary material, which is available to authorized users.",2014 Aug 28,"['Vidaña, Beatriz', 'Martínez, Jorge', 'Martínez-Orellana, Pamela', 'García Migura, Lourdes', 'Montoya, María', 'Martorell, Jaime', 'Majó, Natàlia']",Vet Res,,,True
44e1e81a18b18799c1ab86e439050fff057897d4,PMC,Progress and challenges of disaster health management in China: a scoping review,http://dx.doi.org/10.3402/gha.v7.24986,PMC4161949,25215910,CC BY,"BACKGROUND: Despite the importance of an effective health system response to various disasters, relevant research is still in its infancy, especially in middle- and low-income countries. OBJECTIVE: This paper provides an overview of the status of disaster health management in China, with its aim to promote the effectiveness of the health response for reducing disaster-related mortality and morbidity. DESIGN: A scoping review method was used to address the recent progress of and challenges to disaster health management in China. Major health electronic databases were searched to identify English and Chinese literature that were relevant to the research aims. RESULTS: The review found that since 2003 considerable progress has been achieved in the health disaster response system in China. However, there remain challenges that hinder effective health disaster responses, including low standards of disaster-resistant infrastructure safety, the lack of specific disaster plans, poor emergency coordination between hospitals, lack of portable diagnostic equipment and underdeveloped triage skills, surge capacity, and psychological interventions. Additional challenges include the fragmentation of the emergency health service system, a lack of specific legislation for emergencies, disparities in the distribution of funding, and inadequate cost-effective considerations for disaster rescue. CONCLUSIONS: One solution identified to address these challenges appears to be through corresponding policy strategies at multiple levels (e.g. community, hospital, and healthcare system level).",2014 Sep 10,"['Zhong, Shuang', 'Clark, Michele', 'Hou, Xiang-Yu', 'Zang, Yuli', 'FitzGerald, Gerard']",Glob Health Action,,,True
1a8daad89d2701b4cf603e668f6aab1209b6237e,PMC,Autoreactivity to Glucose Regulated Protein 78 Links Emphysema and Osteoporosis in Smokers,http://dx.doi.org/10.1371/journal.pone.0105066,PMC4162538,25216103,CC BY,"RATIONALE: Emphysema and osteoporosis are epidemiologically associated diseases of cigarette smokers. The causal mechanism(s) linking these illnesses is unknown. We hypothesized autoimmune responses may be involved in both disorders. OBJECTIVES: To discover an antigen-specific autoimmune response associated with both emphysema and osteoporosis among smokers. METHODS: Replicate nonbiased discovery assays indicated that autoimmunity to glucose regulated protein 78 (GRP78), an endoplasmic reticulum chaperone and cell surface signaling receptor, is present in many smokers. Subject assessments included spirometry, chest CT scans, dual x-ray absorptiometry, and immunoblots for anti-GRP78 IgG. Anti-GRP78 autoantibodies were isolated from patient plasma by affinity chromatography, leukocyte functions assessed by flow cytometry, and soluble metabolites and mediators measured by immunoassays. MEASUREMENTS AND MAIN RESULTS: Circulating anti-GRP78 IgG autoantibodies were detected in plasma specimens from 86 (32%) of the 265 smoking subjects. Anti-GRP78 autoantibodies were singularly prevalent among subjects with radiographic emphysema (OR 3.1, 95%CI 1.7–5.7, p = 0.003). Anti-GRP78 autoantibodies were also associated with osteoporosis (OR 4.7, 95%CI 1.7–13.3, p = 0.002), and increased circulating bone metabolites (p = 0.006). Among emphysematous subjects, GRP78 protein was an autoantigen of CD4 T-cells, stimulating lymphocyte proliferation (p = 0.0002) and IFN-gamma production (p = 0.03). Patient-derived anti-GRP78 autoantibodies had avidities for osteoclasts and macrophages, and increased macrophage NFkB phosphorylation (p = 0.005) and productions of IL-8, CCL-2, and MMP9 (p = 0.005, 0.007, 0.03, respectively). CONCLUSIONS: Humoral and cellular GRP78 autoimmune responses in smokers have numerous biologically-relevant pro-inflammatory and other deleterious actions, and are associated with emphysema and osteoporosis. These findings may have relevance for the pathogenesis of smoking-associated diseases, and development of biomarker immunoassays and/or novel treatments for these disorders.",2014 Sep 12,"['Bon, Jessica', 'Kahloon, Rehan', 'Zhang, Yingze', 'Xue, Jianmin', 'Fuhrman, Carl R.', 'Tan, Jiangning', 'Burger, Mathew', 'Kass, Daniel J.', 'Csizmadia, Eva', 'Otterbein, Leo', 'Chandra, Divay', 'Bhargava, Arpit', 'Pilewski, Joseph M.', 'Roodman, G. David', 'Sciurba, Frank C.', 'Duncan, Steven R.']",PLoS One,,,True
bff6e0b359144d2d7f0a1911dc76443c979690b7,PMC,"Isolation and characterization of 11 novel microsatellite loci in a West African leaf-nosed bat, Hipposideros aff. ruber",http://dx.doi.org/10.1186/1756-0500-7-607,PMC4162931,25189128,CC BY,"BACKGROUND: Noack’s leaf-nosed bat, Hipposideros ruber, is a cryptic species within the Hipposideros caffer species complex. Despite a widespread distribution in Africa and being host to potentially zoonotic viruses, the genetic structure and ecology of H. ruber is poorly known. Here we describe the development of 11 novel polymorphic microsatellite loci to facilitate the investigation of genetic structure. FINDINGS: We selected 20 microsatellite sequences identified from high throughput sequence reads and PCR amplified these for 38 individuals, yielding 11 consistently amplifying and scorable loci. The number of alleles per locus ranged from two to 12, and observed heterozygosities from 0.00 to 0.865. No evidence of linkage disequilibrium was observed, and nine of the markers showed no departure from Hardy-Weinberg equilibrium. We demonstrate successful amplification in two closely related species and two divergent lineages of the H. caffer species complex. CONCLUSIONS: These new markers will provide a valuable tool to investigate genetic structure in the poorly understood Hipposideros caffer species complex.",2014 Sep 4,"['Baldwin, Heather J', 'Vallo, Peter', 'Gardner, Michael G', 'Drosten, Christian', 'Tschapka, Marco', 'Stow, Adam J']",BMC Res Notes,,,True
482ceb8b002b0c3f8ec6f26fc0093dd90cec2b0c,PMC,Bioassay Directed Isolation and Biological Evaluation of Compounds Isolated from Rubus fairholmianus Gard.,http://dx.doi.org/10.1155/2014/204340,PMC4165380,25254204,CC BY,"The in vitro and in silico analysis of Rubus fairholmianus acetone extract for antioxidant, antiproliferative, and anti-inflammatory activity led to the isolation of six compounds. Amongst all the six isolated compounds tested, 1-(2-hydroxyphenyl)-4-methylpentan-1-one (compound 1) and 2-[(3-methylbutoxy) carbonyl] benzoic acid (compound 2) were found to be more active in inhibiting BRCA and COX target proteins, which also showed the better results for DPPH and ABTS radical scavenging assays. The promising results of this investigation emphasize the importance of using R. fairholmianus in the treatment of radical generated disorders mainly cancer and other inflammatory diseases.",2014 Sep 1,"['Plackal George, Blassan', 'Thangaraj, Parimelazhagan', 'Sulaiman, Cheruthazhakkatt', 'Piramanayagam, Shanmughavel', 'Ramaswamy, Sathish Kumar']",Biomed Res Int,,,True
2ab5a9cc48131a2a4fc4c2e8be6fabc68aa6397c,PMC,Predictors of Mortality in Mechanically Ventilated Critical Pertussis in a low Income Country,http://dx.doi.org/10.4084/MJHID.2014.059,PMC4165494,25237472,CC BY,"BACKGROUND: Critical pertussis is characterized by severe respiratory failure, important leukocytosis, pulmonary hypertension, septic shock and encephalopathy. AIM: To describe the clinical course of critical pertussis, and identify predictors of death at the time of presentation for medical care. METHODOLOGY: Retrospective study conducted in children’s hospital Tunisian PICU between 01 January and 31 October 2013. Patients with critical pertussis confirmed by RT-PCR and requiring mechanical ventilation were included. Predictors of death were studied. RESULTS: A total of 17 patients was studied. Median age was 50 days. Mortality was 23%. Predictors risk of mortality were : high PRISM score (Pediatric Risk of Mortality Score) (p=0,007), shock (p=0,002), tachycardia (p=0,005), seizures (p=0,006), altered mental status (p=0,006), elevated WBC count (p=0,003) and hemodynamic support (p=0022). However, the difference did not reach statistical significance in comorbidity, pneumoniae, high pulmonary hypertension or exchange transfusion. Concomitant viral or bacterial co-infection was not related to poor outcome. CONCLUSION: Young infants are at high risk to have critical pertussis. Despite advances in life support and the treatment of organ failure in childhood critical illness, critical pertussis remains difficult to treat.",2014 Sep 1,"['Borgi, Aida', 'Menif, Khaled', 'Belhadj, Sarra', 'Ghali, Narjess', 'Salmen, Loukil', 'Hamdi, Asma', 'Khaldi, Ammar', 'Bouaffsoun, Aida', 'Kechaou, Sonia', 'Kechrid, Amel', 'Bouziri, Asma', 'Benjaballah, Nejla']",Mediterr J Hematol Infect Dis,,,True
9fc349caa11e13a92c959d5f8b1669f4b425e2d2,PMC,Autophagic effects of Chaihu (dried roots of Bupleurum Chinense DC or Bupleurum scorzoneraefolium WILD),http://dx.doi.org/10.1186/1749-8546-9-21,PMC4165614,25228909,CC BY,"Chaihu, prepared from the dried roots of Bupleurum Chinense DC (also known as bei Chaihu in Chinese) or Bupleurum scorzoneraefolium WILD (also known as nan Chaihu in Chinese), is a herbal medicine for harmonizing and soothing gan (liver) qi stagnation. Substantial pharmacological studies have been conducted on Chaihu and its active components (saikosaponins). One of the active components of Chaihu, saikosaponin-d, exhibited anticancer effects via autophagy induction. This article reviews the pharmacological findings for the roles of autophagy in the pharmacological actions of Chaihu and saikosaponins.",2014 Sep 11,"['Law, Betty Yuen-Kwan', 'Mo, Jing-Fang', 'Wong, Vincent Kam-Wai']",Chin Med,,,True
d0bb873b6eb934aefa7743cd2fb095c7e3318410,PMC,Dendritic Cells from Aged Subjects Display Enhanced Inflammatory Responses to Chlamydophila pneumoniae,http://dx.doi.org/10.1155/2014/436438,PMC4165882,25253920,CC BY,"Chlamydophila pneumoniae (CPn) is a common respiratory pathogen that causes a chronic and persistent airway infection. The elderly display an increased susceptibility and severity to this infection. However, the underlying mechanisms are not well understood. Dendritic cells (DCs) are the initiators and regulators of immune responses. Therefore, we investigated the role of DCs in the age-associated increased CPn infection in vitro in humans. Though the expression of activation markers was comparable between the two age groups, DCs from aged subjects secreted enhanced levels of proinflammatory mediators such as TNF-α and CXCL-10 in response to CPn. In contrast, the secretion of IL-10 and innate interferons, IFN-α and IFN-λ, was severely impaired in DCs from aged donors. The increased activation of DCs from aged subjects to CPn also resulted in enhanced proliferation of CD4 and CD8 T cells in a DC-T coculture. Furthermore, T cells primed with CPn-stimulated DCs from aged subjects secreted increased levels of IFN-γ and reduced levels of IL-10 compared to DCs obtained from young subjects. In summary, DCs from the elderly displayed enhanced inflammatory response to CPn which may result in airway remodeling and increase the susceptibility of the elderly to respiratory diseases such as asthma.",2014 Sep 1,"['Prakash, Sangeetha', 'Agrawal, Sudhanshu', 'Ma, Dandan', 'Gupta, Sudhir', 'Peterson, Ellena M.', 'Agrawal, Anshu']",Mediators Inflamm,,,False
a7bb5432ed9fc93c11b893bd499bb66becfc71f6,PMC,Dendritic Cells from Aged Subjects Display Enhanced Inflammatory Responses to Chlamydophila pneumoniae,http://dx.doi.org/10.1155/2014/436438,PMC4165882,25253920,CC BY,"Chlamydophila pneumoniae (CPn) is a common respiratory pathogen that causes a chronic and persistent airway infection. The elderly display an increased susceptibility and severity to this infection. However, the underlying mechanisms are not well understood. Dendritic cells (DCs) are the initiators and regulators of immune responses. Therefore, we investigated the role of DCs in the age-associated increased CPn infection in vitro in humans. Though the expression of activation markers was comparable between the two age groups, DCs from aged subjects secreted enhanced levels of proinflammatory mediators such as TNF-α and CXCL-10 in response to CPn. In contrast, the secretion of IL-10 and innate interferons, IFN-α and IFN-λ, was severely impaired in DCs from aged donors. The increased activation of DCs from aged subjects to CPn also resulted in enhanced proliferation of CD4 and CD8 T cells in a DC-T coculture. Furthermore, T cells primed with CPn-stimulated DCs from aged subjects secreted increased levels of IFN-γ and reduced levels of IL-10 compared to DCs obtained from young subjects. In summary, DCs from the elderly displayed enhanced inflammatory response to CPn which may result in airway remodeling and increase the susceptibility of the elderly to respiratory diseases such as asthma.",2014 Sep 1,"['Prakash, Sangeetha', 'Agrawal, Sudhanshu', 'Ma, Dandan', 'Gupta, Sudhir', 'Peterson, Ellena M.', 'Agrawal, Anshu']",Mediators Inflamm,,,True
d1ecd2ec6f1030c8e1ba1844e0fea59b19267a55,PMC,Global health diplomacy: advancing foreign policy and global health interests,http://dx.doi.org/10.9745/GHSP-D-12-00048,PMC4168555,25276514,CC BY,"Attention to global health diplomacy has been rising but the future holds challenges, including a difficult budgetary environment. Going forward, both global health and foreign policy practitioners would benefit from working more closely together to achieve greater mutual understanding and to advance respective mutual goals.",2013 Mar 21,"['Michaud, Josh', 'Kates, Jennifer']",Glob Health Sci Pract,,,True
12cbf7162f5525c020e909c85db4142007c64603,PMC,"Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications",http://dx.doi.org/10.3762/bjoc.10.200,PMC4168895,25246951,CC BY,"(1H-Benzo[d][1,2,3]triazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 1H-benzo[d][1,2,3]triazol-1-yl 4-methylbenzenesulfonate (Bt-OTs), and 3H-[1,2,3]triazolo[4,5-b]pyridine-3-yl 4-methylbenzenesulfonate (At-OTs) are classically utilized in peptide synthesis for amide-bond formation. However, a previously undescribed reaction of these compounds with alcohols in the presence of a base, leads to 1-alkoxy-1H-benzo- (Bt-OR) and 7-azabenzotriazoles (At-OR). Although BOP undergoes reactions with alcohols to furnish 1-alkoxy-1H-benzotriazoles, Bt-OTs proved to be superior. Both, primary and secondary alcohols undergo reaction under generally mild reaction conditions. Correspondingly, 1-alkoxy-1H-7-azabenzotriazoles were synthesized from At-OTs. Mechanistically, there are three pathways by which these peptide-coupling agents can react with alcohols. From (31)P{(1)H}, [(18)O]-labeling, and other chemical experiments, phosphonium and tosylate derivatives of alcohols seem to be intermediates. These then react with BtO(−) and AtO(−) produced in situ. In order to demonstrate broader utility, this novel reaction has been used to prepare a series of acyclic nucleoside-like compounds. Because BtO(−) is a nucleofuge, several Bt-OCH(2)Ar substrates have been evaluated in nucleophilic substitution reactions. Finally, the possible formation of Pd π–allyl complexes by departure of BtO(−) has been queried. Thus, alpha-allylation of three cyclic ketones was evaluated with 1-(cinnamyloxy)-1H-benzo[d][1,2,3]triazole, via in situ formation of pyrrolidine enamines and Pd catalysis.",2014 Aug 19,"['Lakshman, Mahesh K', 'Singh, Manish K', 'Kumar, Mukesh', 'Chamala, Raghu Ram', 'Yedulla, Vijayender R', 'Wagner, Domenick', 'Leung, Evan', 'Yang, Lijia', 'Matin, Asha', 'Ahmad, Sadia']",Beilstein J Org Chem,,,True
c33d7d8d49ed2a2ea4c997f587e75b9723418226,PMC,"Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications",http://dx.doi.org/10.3762/bjoc.10.200,PMC4168895,25246951,CC BY,"(1H-Benzo[d][1,2,3]triazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 1H-benzo[d][1,2,3]triazol-1-yl 4-methylbenzenesulfonate (Bt-OTs), and 3H-[1,2,3]triazolo[4,5-b]pyridine-3-yl 4-methylbenzenesulfonate (At-OTs) are classically utilized in peptide synthesis for amide-bond formation. However, a previously undescribed reaction of these compounds with alcohols in the presence of a base, leads to 1-alkoxy-1H-benzo- (Bt-OR) and 7-azabenzotriazoles (At-OR). Although BOP undergoes reactions with alcohols to furnish 1-alkoxy-1H-benzotriazoles, Bt-OTs proved to be superior. Both, primary and secondary alcohols undergo reaction under generally mild reaction conditions. Correspondingly, 1-alkoxy-1H-7-azabenzotriazoles were synthesized from At-OTs. Mechanistically, there are three pathways by which these peptide-coupling agents can react with alcohols. From (31)P{(1)H}, [(18)O]-labeling, and other chemical experiments, phosphonium and tosylate derivatives of alcohols seem to be intermediates. These then react with BtO(−) and AtO(−) produced in situ. In order to demonstrate broader utility, this novel reaction has been used to prepare a series of acyclic nucleoside-like compounds. Because BtO(−) is a nucleofuge, several Bt-OCH(2)Ar substrates have been evaluated in nucleophilic substitution reactions. Finally, the possible formation of Pd π–allyl complexes by departure of BtO(−) has been queried. Thus, alpha-allylation of three cyclic ketones was evaluated with 1-(cinnamyloxy)-1H-benzo[d][1,2,3]triazole, via in situ formation of pyrrolidine enamines and Pd catalysis.",2014 Aug 19,"['Lakshman, Mahesh K', 'Singh, Manish K', 'Kumar, Mukesh', 'Chamala, Raghu Ram', 'Yedulla, Vijayender R', 'Wagner, Domenick', 'Leung, Evan', 'Yang, Lijia', 'Matin, Asha', 'Ahmad, Sadia']",Beilstein J Org Chem,,,True
4141cdba2be695f11c3f7278d72481ae521eebd9,PMC,"Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications",http://dx.doi.org/10.3762/bjoc.10.200,PMC4168895,25246951,CC BY,"(1H-Benzo[d][1,2,3]triazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 1H-benzo[d][1,2,3]triazol-1-yl 4-methylbenzenesulfonate (Bt-OTs), and 3H-[1,2,3]triazolo[4,5-b]pyridine-3-yl 4-methylbenzenesulfonate (At-OTs) are classically utilized in peptide synthesis for amide-bond formation. However, a previously undescribed reaction of these compounds with alcohols in the presence of a base, leads to 1-alkoxy-1H-benzo- (Bt-OR) and 7-azabenzotriazoles (At-OR). Although BOP undergoes reactions with alcohols to furnish 1-alkoxy-1H-benzotriazoles, Bt-OTs proved to be superior. Both, primary and secondary alcohols undergo reaction under generally mild reaction conditions. Correspondingly, 1-alkoxy-1H-7-azabenzotriazoles were synthesized from At-OTs. Mechanistically, there are three pathways by which these peptide-coupling agents can react with alcohols. From (31)P{(1)H}, [(18)O]-labeling, and other chemical experiments, phosphonium and tosylate derivatives of alcohols seem to be intermediates. These then react with BtO(−) and AtO(−) produced in situ. In order to demonstrate broader utility, this novel reaction has been used to prepare a series of acyclic nucleoside-like compounds. Because BtO(−) is a nucleofuge, several Bt-OCH(2)Ar substrates have been evaluated in nucleophilic substitution reactions. Finally, the possible formation of Pd π–allyl complexes by departure of BtO(−) has been queried. Thus, alpha-allylation of three cyclic ketones was evaluated with 1-(cinnamyloxy)-1H-benzo[d][1,2,3]triazole, via in situ formation of pyrrolidine enamines and Pd catalysis.",2014 Aug 19,"['Lakshman, Mahesh K', 'Singh, Manish K', 'Kumar, Mukesh', 'Chamala, Raghu Ram', 'Yedulla, Vijayender R', 'Wagner, Domenick', 'Leung, Evan', 'Yang, Lijia', 'Matin, Asha', 'Ahmad, Sadia']",Beilstein J Org Chem,,,True
e24bf8c23979d56fff33bd4ed96fb00a117f701b,PMC,A New Approach for Monitoring Ebolavirus in Wild Great Apes,http://dx.doi.org/10.1371/journal.pntd.0003143,PMC4169258,25232832,CC0,"BACKGROUND: Central Africa is a “hotspot” for emerging infectious diseases (EIDs) of global and local importance, and a current outbreak of ebolavirus is affecting multiple countries simultaneously. Ebolavirus is suspected to have caused recent declines in resident great apes. While ebolavirus vaccines have been proposed as an intervention to protect apes, their effectiveness would be improved if we could diagnostically confirm Ebola virus disease (EVD) as the cause of die-offs, establish ebolavirus geographical distribution, identify immunologically naïve populations, and determine whether apes survive virus exposure. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the first successful noninvasive detection of antibodies against Ebola virus (EBOV) from wild ape feces. Using this method, we have been able to identify gorillas with antibodies to EBOV with an overall prevalence rate reaching 10% on average, demonstrating that EBOV exposure or infection is not uniformly lethal in this species. Furthermore, evidence of antibodies was identified in gorillas thought previously to be unexposed to EBOV (protected from exposure by rivers as topological barriers of transmission). CONCLUSIONS/SIGNIFICANCE: Our new approach will contribute to a strategy to protect apes from future EBOV infections by early detection of increased incidence of exposure, by identifying immunologically naïve at-risk populations as potential targets for vaccination, and by providing a means to track vaccine efficacy if such intervention is deemed appropriate. Finally, since human EVD is linked to contact with infected wildlife carcasses, efforts aimed at identifying great ape outbreaks could have a profound impact on public health in local communities, where EBOV causes case-fatality rates of up to 88%.",2014 Sep 18,"['Reed, Patricia E.', 'Mulangu, Sabue', 'Cameron, Kenneth N.', 'Ondzie, Alain U.', 'Joly, Damien', 'Bermejo, Magdalena', 'Rouquet, Pierre', 'Fabozzi, Giulia', 'Bailey, Michael', 'Shen, Zhimin', 'Keele, Brandon F.', 'Hahn, Beatrice', 'Karesh, William B.', 'Sullivan, Nancy J.']",PLoS Negl Trop Dis,,,True
95e8817d39f27e9ae56bf7b2bb8f4f8bf3c9dd19,PMC,A New Approach for Monitoring Ebolavirus in Wild Great Apes,http://dx.doi.org/10.1371/journal.pntd.0003143,PMC4169258,25232832,CC0,"BACKGROUND: Central Africa is a “hotspot” for emerging infectious diseases (EIDs) of global and local importance, and a current outbreak of ebolavirus is affecting multiple countries simultaneously. Ebolavirus is suspected to have caused recent declines in resident great apes. While ebolavirus vaccines have been proposed as an intervention to protect apes, their effectiveness would be improved if we could diagnostically confirm Ebola virus disease (EVD) as the cause of die-offs, establish ebolavirus geographical distribution, identify immunologically naïve populations, and determine whether apes survive virus exposure. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the first successful noninvasive detection of antibodies against Ebola virus (EBOV) from wild ape feces. Using this method, we have been able to identify gorillas with antibodies to EBOV with an overall prevalence rate reaching 10% on average, demonstrating that EBOV exposure or infection is not uniformly lethal in this species. Furthermore, evidence of antibodies was identified in gorillas thought previously to be unexposed to EBOV (protected from exposure by rivers as topological barriers of transmission). CONCLUSIONS/SIGNIFICANCE: Our new approach will contribute to a strategy to protect apes from future EBOV infections by early detection of increased incidence of exposure, by identifying immunologically naïve at-risk populations as potential targets for vaccination, and by providing a means to track vaccine efficacy if such intervention is deemed appropriate. Finally, since human EVD is linked to contact with infected wildlife carcasses, efforts aimed at identifying great ape outbreaks could have a profound impact on public health in local communities, where EBOV causes case-fatality rates of up to 88%.",2014 Sep 18,"['Reed, Patricia E.', 'Mulangu, Sabue', 'Cameron, Kenneth N.', 'Ondzie, Alain U.', 'Joly, Damien', 'Bermejo, Magdalena', 'Rouquet, Pierre', 'Fabozzi, Giulia', 'Bailey, Michael', 'Shen, Zhimin', 'Keele, Brandon F.', 'Hahn, Beatrice', 'Karesh, William B.', 'Sullivan, Nancy J.']",PLoS Negl Trop Dis,,,False
0fb7458693f388bce5927bb1f9be866eb36b6349,PMC,Association of Cytokines in Individuals Sensitive and Insensitive to Dust Mites in a Brazilian Population,http://dx.doi.org/10.1371/journal.pone.0107921,PMC4169580,25238536,CC BY,"INTRODUCTION: Allergic reaction to dust mites is a relatively common condition among children, triggering cutaneous and respiratory responses that have a great impact on the health of this population. Anaphylactic hypersensitivity is characterized by an exacerbated response involving the production of regulatory cytokines responsible for stimulating the production of IgE antibodies. OBJECTIVE: To investigate an association of variants in cytokine genes (IL1A (−889), IL1B (−511, +3962), IL1R (1970), IL1RA (11100), IL4RA (+1902), IL12 (−1188), IFNG (+874), TGFB1 (codon 10, codon 25), TNFA (−308, −238), IL2 (−330, +166), IL4 (−1098, −590, −33), IL6 (−174, nt565), and IL10 (−1082, −819, −592)) between patients sensitive to dust mites and a control group. METHODS: A total of 254 patients were grouped as atopic and non-atopic according to sensitivity as evaluated by the Prick Test and to cytokine genotyping by the polymerase chain reaction-sequence specific primers (PCR-SSP) method using the Cytokine Genotyping Kit. RESULTS: A comparison between individuals allergic to Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Blomia tropicalis and a non-atopic control group showed significant differences between allele and genotype frequencies in the regulatory regions of cytokine genes, with important evidence for IL4 (−590) in T/C (10.2% vs. 43.1%, odd ratio [OR] = 0.15, p = 5.2 10(−8), pc = 0.0000011, and 95% confidence interval [95%CI] = 0.07–0.32) and T/T genotypes (42.9% vs. 13.8%, OR = 4.69, p = 2.5 10(−6), pc = 0.000055, and 95%CI = 2.42–9.09). Other associations were observed in the pro-inflammatory cytokines IL1A (−889) (T/T, C, and T) and IL2 (−330) (G/T and T/T) and the anti-inflammatory cytokines IL4RA (+1902) (A and G), IL4 (−590) (T/C, T/T, C, and T), and IL10 (−592) (A/A, C/A, A, and C). CONCLUSION: Our results suggest a possible association between single nucleotide polymorphisms (SNPs) in cytokine genes and hypersensitivity to dust mites.",2014 Sep 19,"['Caniatti, Marcela Caleffi da Costa Lima', 'Marchioro, Ariella Andrade', 'Guilherme, Ana Lúcia Falavigna', 'Tsuneto, Luiza Tamie']",PLoS One,,,True
f33e644d058bc8373378c115878be06346298687,PMC,"Docetaxel induces moderate ovarian toxicity in mice, primarily affecting granulosa cells of early growing follicles",http://dx.doi.org/10.1093/molehr/gau057,PMC4172173,25080441,CC BY,"Advances in cancer therapy have focused attention on the quality of life of cancer survivors. Since infertility is a major concern following chemotherapy, it is important to characterize the drug-specific damage to the reproductive system to help find appropriate protective strategies. This study investigates the damage on neonatal mouse ovary maintained in vitro for 6 days, and exposed for 24 h (on Day 2) to clinically relevant doses of Docetaxel (DOC; low: 0.1 µM, mid: 1 µM, high: 10 µM). Furthermore, the study explores the putative protective action exerted by Tri-iodothyronine (T3; 10(−7) M). At the end of culture, morphological analyses and follicle counts showed that DOC negatively impacts on early growing follicles, decreasing primary follicle number and severely affecting health at the transitional and primary stages. Poor follicle health was mainly due to effects on granulosa cells, indicating that the effects of DOC on oocytes were likely to be secondary to granulosa cell damage. DOC damages growing follicles specifically, with no direct effect on the primordial follicle reserve. Immunostaining and western blotting showed that DOC induces activation of intrinsic, type II apoptosis in ovarian somatic cells; increasing the levels of cleaved caspase 3, cleaved caspase 8, Bax and cleaved poly(ADP-ribose) polymerase, while also inducing movement of cytochrome C from mitochondria into the cytosol. T3 did not prevent the damage induced by the low dose of DOC. These results demonstrated that DOC induces a gonadotoxic effect on the mouse ovary through induction of somatic cell apoptosis, with no evidence of direct effects on the oocyte, and that the damaging effect is not mitigated by T3.",2014 Oct 30,"['Lopes, Federica', 'Smith, Rowena', 'Anderson, Richard A.', 'Spears, Norah']",Mol Hum Reprod,,,True
7c1b1700315cc018b94e1488667365315137cb20,PMC,Rapid and sensitive detection of canine distemper virus by one-tube reverse transcription-insulated isothermal polymerase chain reaction,http://dx.doi.org/10.1186/s12917-014-0213-8,PMC4172905,25200113,CC BY,"BACKGROUND: Canine distemper virus (CDV) has been associated with outbreaks of canine infectious respiratory disease in shelters and boarding kennel environments. POCKIT(TM) Nucleic Acid Analyzer is a field-deployable device capable of generating automatically interpreted insulated isothermal polymerase chain reaction (iiPCR) results from extracted nucleic acid within one hour. In this study, reverse transcription iiPCR (RT-iiPCR) was developed to facilitate point-of-need diagnosis of CDV infection. RESULTS: Analytical sensitivity (limit of detection 95%) of the established CDV RT-iiPCR was about 11 copies of in vitro transcribed RNA per reaction. CDV RT-iiPCR generated positive signals from CDV, but not Bordetella bronchiseptica, canine parvovirus, canine herpesvirus, canine adenovirus 2, canine influenza virus (subtype H3N8), canine parainfluenza virus, and canine respiratory coronavirus. To evaluate accuracy of the established reaction in canine distemper clinical diagnosis, 110 specimens from dogs, raccoons, and foxes suspected with CDV infection were tested simultaneously by CDV RT-iiPCR and real-time RT-PCR. CDV RT-iiPCR demonstrated excellent sensitivity (100%) and specificity (100%), compared to real-time RT-PCR. CONCLUSIONS: The results indicated an excellent correlation between RT-iiPCR and a reference real time RT-PCR method. Working in a lyophilized format, the established method has great potential to be used for point-of-care diagnosis of canine distemper in animals, especially in resource-limited facilities.",2014 Sep 9,"['Wilkes, Rebecca P', 'Tsai, Yun-Long', 'Lee, Pei-Yu', 'Lee, Fu-Chun', 'Chang, Hsiao-Fen Grace', 'Wang, Hwa-Tang Thomas']",BMC Vet Res,,,True
468c549a9b35a3f23be71f098c3ab910abadac8d,PMC,"Management of the slowly emerging zoonosis, Hendra virus, by private veterinarians in Queensland, Australia: a qualitative study",http://dx.doi.org/10.1186/s12917-014-0215-6,PMC4173005,25224910,CC BY,"BACKGROUND: Veterinary infection control for the management of Hendra virus (HeV), an emerging zoonosis in Australia, remained suboptimal until 2010 despite 71.4% (5/7) of humans infected with HeV being veterinary personnel or assisting a veterinarian, three of whom died before 2009. The aim of this study was to identify the perceived barriers to veterinary infection control and HeV management in private veterinary practice in Queensland, where the majority of HeV outbreaks have occurred in Australia. RESULTS: Most participants agreed that a number of key factors had contributed to the slow uptake of adequate infection control measures for the management of HeV amongst private veterinarians: a work culture characterised by suboptimal infection control standards and misconceptions about zoonotic risks; a lack of leadership and support from government authorities; the difficulties of managing biosecurity and public health issues from a private workforce perspective; and the slow pattern of emergence of HeV. By 2010, some infection control and HeV management changes had been implemented. Participants interviewed agreed that further improvements remained necessary; but also cautioned that this was a complex process which would require time. CONCLUSION: Private veterinarians and government authorities prior to 2009 were unprepared to handle new slowly emerging zoonoses, which may explain their mismanagement of HeV. Slowly emerging zoonoses may be of low public health significance but of high significance for specialised groups such as veterinarians. Private veterinarians, who are expected to fulfil an active biosecurity and public health role in the frontline management of such emerging zoonoses, need government agencies to better recognise their contribution, to consult with the veterinary profession when devising guidelines for the management of zoonoses and to provide them with greater leadership and support. We propose that specific infection control guidelines for the management of slowly emerging zoonoses in private veterinary settings need to be developed.",2014 Sep 17,"['Mendez, Diana H', 'Kelly, Jenny', 'Buttner, Petra', 'Nowak, Madeleine', 'Speare, Rick']",BMC Vet Res,,,True
3dede13dfa857e159c3fd7830374e1dc76008f2e,PMC,A novel porcine reproductive and respiratory syndrome virus vector system that stably expresses enhanced green fluorescent protein as a separate transcription unit,http://dx.doi.org/10.1186/1297-9716-44-104,PMC4176086,24176053,CC BY,"Here we report the rescue of a recombinant porcine reproductive and respiratory syndrome virus (PRRSV) carrying an enhanced green fluorescent protein (EGFP) reporter gene as a separate transcription unit. A copy of the transcription regulatory sequence for ORF6 (TRS6) was inserted between the N protein and 3′-UTR to drive the transcription of the EGFP gene and yield a general purpose expression vector. Successful recovery of PRRSV was obtained using an RNA polymerase II promoter to drive transcription of the full-length virus genome, which was assembled in a bacterial artificial chromosome (BAC). The recombinant virus showed growth replication characteristics similar to those of the wild-type virus in the infected cells. In addition, the recombinant virus stably expressed EGFP for at least 10 passages. EGFP expression was detected at approximately 10 h post infection by live-cell imaging to follow the virus spread in real time and the infection of neighbouring cells occurred predominantly through cell-to-cell-contact. Finally, the recombinant virus generated was found to be an excellent tool for neutralising antibodies and antiviral compound screening. The newly established reverse genetics system for PRRSV could be a useful tool not only to monitor virus spread and screen for neutralising antibodies and antiviral compounds, but also for fundamental research on the biology of the virus.",2013 Oct 31,"['Wang, Chengbao', 'Huang, Baicheng', 'Kong, Ning', 'Li, Qiongyi', 'Ma, Yuping', 'Li, Zhijun', 'Gao, Jiming', 'Zhang, Chong', 'Wang, Xiangpeng', 'Liang, Chao', 'Dang, Lu', 'Xiao, Shuqi', 'Mu, Yang', 'Zhao, Qin', 'Sun, Yani', 'Almazan, Fernando', 'Enjuanes, Luis', 'Zhou, En-Min']",Vet Res,,,True
9ac01047c360e0def0d96adf2e59f6e5bd68b3b7,PMC,Photodynamic Antimicrobial Polymers for Infection Control,http://dx.doi.org/10.1371/journal.pone.0108500,PMC4177408,25250740,CC BY,"Hospital-acquired infections pose both a major risk to patient wellbeing and an economic burden on global healthcare systems, with the problem compounded by the emergence of multidrug resistant and biocide tolerant bacterial pathogens. Many inanimate surfaces can act as a reservoir for infection, and adequate disinfection is difficult to achieve and requires direct intervention. In this study we demonstrate the preparation and performance of materials with inherent photodynamic, surface-active, persistent antimicrobial properties through the incorporation of photosensitizers into high density poly(ethylene) (HDPE) using hot-melt extrusion, which require no external intervention except a source of visible light. Our aim is to prevent bacterial adherence to these surfaces and eliminate them as reservoirs of nosocomial pathogens, thus presenting a valuable advance in infection control. A two-layer system with one layer comprising photosensitizer-incorporated HDPE, and one layer comprising HDPE alone is also described to demonstrate the versatility of our approach. The photosensitizer-incorporated materials are capable of reducing the adherence of viable bacteria by up to 3.62 Log colony forming units (CFU) per square centimeter of material surface for methicillin resistant Staphylococcus aureus (MRSA), and by up to 1.51 Log CFU/cm(2) for Escherichia coli. Potential applications for the technology are in antimicrobial coatings for, or materials comprising objects, such as tubing, collection bags, handrails, finger-plates on hospital doors, or medical equipment found in the healthcare setting.",2014 Sep 24,"['McCoy, Colin P.', 'O’Neil, Edward J.', 'Cowley, John F.', 'Carson, Louise', 'De Baróid, Áine T.', 'Gdowski, Greg T.', 'Gorman, Sean P.', 'Jones, David S.']",PLoS One,,,True
b5a7acc938d3d05c5ef67cb6b1dd090805e487e5,PMC,Roles of the antioxidant properties of icariin and its phosphorylated derivative in the protection against duck virus hepatitis,http://dx.doi.org/10.1186/s12917-014-0226-3,PMC4177705,25244948,CC BY,"BACKGROUND: Duck viral hepatitis (DVH) is an acute disease of young ducklings with few convenient and effective veterinary drugs to treat. In pathology, present study mainly focused on the immune mechanism, but very few studies have concerned with the role of oxidative stress in the pathogenesis of DVH. To study the antioxidative and hepatoprotective effects of icariin and its phosphorylated derivative against DVH, we prepared phosphorylated icariin (p-icariin) using the sodium trimetaphosphate–sodium tripolyphosphate method. Ducklings were drunk with icariin and p-icariin after being challenged with duck hepatitis virus 1 (DHV-1). We recorded the number of dead ducklings, gross pathological changes in the liver, and changes in indices of oxidative stress and liver injury. The correlations between these indices were also analyzed. RESULTS: Exposure to DHV-1 induced significant oxidative damage in ducklings. Administration of icariin or p-icariin attenuated liver pathological injury and significantly increased the survival rate, with better outcomes in ducklings treated with p-icariin than in those treated with icariin. Icariin and p-icariin also attenuated the changes in oxidative stress and liver injury. We found positive correlations among indices of oxidative stress (malondialdehyde and inducible nitric oxide synthase) and liver injury (alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase), suggesting that DHV-1 causes significant oxidative damage, which is related to the extent of hepatic injury. CONCLUSIONS: Icariin and p-icariin improved the survival and attenuated oxidative stress and liver dysfunction induced by DHV-1. These outcomes were better in ducklings treated with p-icariin than in those treated by icariin. The clinical effects of both components were related to their antioxidant activities.",2014 Sep 24,"['Xiong, Wen', 'Chen, Yun', 'Wang, Yu', 'Liu, Jiaguo']",BMC Vet Res,,,True
a825eb21bd4ff17296f2f289faa849d326472b73,PMC,Hospital-based influenza morbidity and mortality surveillance system for influenza-like illnesses: a comparison with national influenza surveillance systems,http://dx.doi.org/10.1111/irv.12175,PMC4177793,24020512,CC BY,"The Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system is an emergency room (ER)-based influenza surveillance system in Korea that was established in 2011. The system was established under the assumption that integrated clinical and virologic surveillance could be performed rapidly and easily at seven tertiary hospitals' ER. Here, we assessed the correlation between data generated from the HIMM surveillance system and the Korean national influenza surveillance systems during the 2011–2012 influenza season using cross-correlation analysis and found strong correlations. Rapid antigen-test-based HIMM surveillance would predict the start of influenza epidemic earlier than pre-existing influenza-like-illness-based surveillance.",2014 Jan 11,"['Seo, Yu Bin', 'Song, Joon Young', 'Cheong, Hee Jin', 'Cho, Young Duck', 'Wie, Seong-Heon', 'Jeong, Hye Won', 'Kim, Woo Joo']",Influenza Other Respir Viruses,,,True
d4f6cfb312bae60aa35168d4a775bdb90c4bc39c,PMC,Respiratory viral infections and effects of meteorological parameters and air pollution in adults with respiratory symptoms admitted to the emergency room,http://dx.doi.org/10.1111/irv.12158,PMC4177797,24034701,CC BY,"BACKGROUND: Respiratory viral infections (RVIs) are the most common causes of respiratory infections. The prevalence of respiratory viruses in adults is underestimated. Meteorological variations and air pollution are likely to play a role in these infections. OBJECTIVES: The objectives of this study were to determine the number of emergency visits for influenza-like illness (ILI) and severe acute respiratory infection (SARI) and to evaluate the association between ILI/SARI, RVI prevalence, and meteorological factors/air pollution, in the city of Porto Alegre, Brazil, from November 2008 to October 2010. METHODS: Eleven thousand nine hundred and fifty-three hospitalizations (adults and children) for respiratory symptoms were correlated with meteorological parameters and air pollutants. In a subset of adults, nasopharyngeal aspirates were collected and analyzed through IFI test. The data were analyzed using time-series analysis. RESULTS: Influenza-like illness and SARI were diagnosed in 3698 (30·9%) and 2063 (17·7%) patients, respectively. Thirty-seven (9·0%) samples were positive by IFI and 93 of 410 (22·7%) were IFI and/or PCR positive. In a multivariate logistic regression model, IFI positivity was statistically associated with absolute humidity, use of air conditioning, and presence of mold in home. Sunshine duration was significantly associated with the frequency of ILI cases. For SARI cases, the variables mean temperature, sunshine duration, relative humidity, and mean concentration of pollutants were singnificant. CONCLUSIONS: At least 22% of infections in adult patients admitted to ER with respiratory complaints were caused by RVI. The correlations among meteorological variables, air pollution, ILI/SARI cases, and respiratory viruses demonstrated the relevance of climate factors as significant underlying contributors to the prevalence of RVI.",2014 Jan 26,"['Silva, Denise R', 'Viana, Vinícius P', 'Müller, Alice M', 'Livi, Fernando P', 'Dalcin, Paulo de Tarso R']",Influenza Other Respir Viruses,,,True
5300635b9c02f28ee26a26ee5547b6bc16cd0139,PMC,Increased cytokine/chemokines in serum from asthmatic and non-asthmatic patients with viral respiratory infection,http://dx.doi.org/10.1111/irv.12155,PMC4177805,23962134,CC BY,"BACKGROUND: Respiratory viral infections can induce different cytokine/chemokine profiles in lung tissues and have a significant influence on patients with asthma. There is little information about the systemic cytokine status in viral respiratory-infected asthmatic patients compared with non-asthmatic patients. OBJECTIVES: The aim of this study was to determine changes in circulating cytokines (IL-1β, TNF-α, IL-4, IL-5) and chemokines (MCP1: monocyte chemoattractant protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in patients with an asthmatic versus a non-asthmatic background with respiratory syncytial virus, parainfluenza virus or adenovirus respiratory infection. In addition, human monocyte cultures were incubated with respiratory viruses to determine the cytokine/chemokine profiles. PATIENTS/METHODS: Patients with asthmatic (n = 34) and non-asthmatic (n = 18) history and respiratory infections with respiratory syncytial virus, parainfluenza, and adenovirus were studied. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in blood and culture supernatants was determined by ELISA. Monocytes were isolated by Hystopaque gradient and cocultured with each of the above-mentioned viruses. RESULTS: Similar increased cytokine concentrations were observed in asthmatic and non-asthmatic patients. However, higher concentrations of chemokines were observed in asthmatic patients. Virus-infected monocyte cultures showed similar cytokine/chemokine profiles to those observed in the patients. CONCLUSIONS: Circulating cytokine profiles induced by acute viral lung infection were not related to asthmatic status, except for chemokines that were already increased in the asthmatic status. Monocytes could play an important role in the increased circulating concentration of cytokines found during respiratory viral infections.",2014 Jan 21,"['Giuffrida, María J', 'Valero, Nereida', 'Mosquera, Jesús', 'Alvarez de Mon, Melchor', 'Chacín, Betulio', 'Espina, Luz Marina', 'Gotera, Jennifer', 'Bermudez, John', 'Mavarez, Alibeth']",Influenza Other Respir Viruses,,,True
590dc551804c7579ac9623ee64f81d1186261faa,PMC,Reorganization of the Endosomal System in Salmonella-Infected Cells: The Ultrastructure of Salmonella-Induced Tubular Compartments,http://dx.doi.org/10.1371/journal.ppat.1004374,PMC4177991,25254663,CC BY,"During the intracellular life of Salmonella enterica, a unique membrane-bound compartment termed Salmonella-containing vacuole, or SCV, is formed. By means of translocated effector proteins, intracellular Salmonella also induce the formation of extensive, highly dynamic membrane tubules termed Salmonella-induced filaments or SIF. Here we report the first detailed ultrastructural analyses of the SCV and SIF by electron microscopy (EM), EM tomography and live cell correlative light and electron microscopy (CLEM). We found that a subset of SIF is composed of double membranes that enclose portions of host cell cytosol and cytoskeletal filaments within its inner lumen. Despite some morphological similarities, we found that the formation of SIF double membranes is independent from autophagy and requires the function of the effector proteins SseF and SseG. The lumen of SIF network is accessible to various types of endocytosed material and our CLEM analysis of double membrane SIF demonstrated that fluid phase markers accumulate only between the inner and outer membrane of these structures, a space continual with endosomal lumen. Our work reveals how manipulation of the endosomal membrane system by an intracellular pathogen results in a unique tubular membrane compartmentalization of the host cell, generating a shielded niche permissive for intracellular proliferation of Salmonella.",2014 Sep 25,"['Krieger, Viktoria', 'Liebl, David', 'Zhang, Yuying', 'Rajashekar, Roopa', 'Chlanda, Petr', 'Giesker, Katrin', 'Chikkaballi, Deepak', 'Hensel, Michael']",PLoS Pathog,,,True
d4b5a78a1ab61e4e94bf8478c47e6f5e2ef33086,PMC,High-Throughput Sequencing and De Novo Assembly of the Isatis indigotica Transcriptome,http://dx.doi.org/10.1371/journal.pone.0102963,PMC4178013,25259890,CC BY,"BACKGROUND: Isatis indigotica, the source of the traditional Chinese medicine Radix isatidis (Ban-Lan-Gen), is an extremely important economical crop in China. To facilitate biological, biochemical and molecular research on the medicinal chemicals in I. indigotica, here we report the first I. indigotica transcriptome generated by RNA sequencing (RNA-seq). RESULTS: RNA-seq library was created using RNA extracted from a mixed sample including leaf and root. A total of 33,238 unigenes were assembled from more than 28 million of high quality short reads. The quality of the assembly was experimentally examined by cDNA sequencing of seven randomly selected unigenes. Based on blast search 28,184 unigenes had a hit in at least one of the protein and nucleotide databases used in this study, and 8 unigenes were found to be associated with biosynthesis of indole and its derivatives. According to Gene Ontology classification, 22,365 unigenes were categorized into 48 functional groups. Furthermore, Clusters of Orthologous Group and Swiss-Port annotation were assigned for 7,707 and 18,679 unigenes, respectively. Analysis of repeat motifs identified 6,400 simple sequence repeat markers in 4,509 unigenes. CONCLUSION: Our data provide a comprehensive sequence resource for molecular study of I. indigotica. Our results will facilitate studies on the functions of genes involved in the indole alkaloid biosynthesis pathway and on metabolism of nitrogen and indole alkaloids in I. indigotica and its related species.",2014 Sep 26,"['Tang, Xiaoqing', 'Xiao, Yunhua', 'Lv, Tingting', 'Wang, Fangquan', 'Zhu, QianHao', 'Zheng, Tianqing', 'Yang, Jie']",PLoS One,,,True
27b5819a442f4af88897625612d73a398b439bfd,PMC,Modulation of Stop Codon Read-Through Efficiency and Its Effect on the Replication of Murine Leukemia Virus,http://dx.doi.org/10.1128/JVI.00898-14,PMC4178896,24991001,CC BY,"Translational readthrough—suppression of termination at a stop codon—is exploited in the replication cycles of several viruses and represents a potential target for antiviral intervention. In the gammaretroviruses, typified by Moloney murine leukemia virus (MuLV), gag and pol are in the same reading frame, separated by a UAG stop codon, and termination codon readthrough is required for expression of the viral Gag-Pol fusion protein. Here, we investigated the effect on MuLV replication of modulating readthrough efficiency. We began by manipulating the readthrough signal in the context of an infectious viral clone to generate a series of MuLV variants in which readthrough was stimulated or reduced. In carefully controlled infectivity assays, it was found that reducing the MuLV readthrough efficiency only 4-fold led to a marked defect and that a 10-fold reduction essentially abolished replication. However, up to an ∼8.5-fold stimulation of readthrough (up to 60% readthrough) was well tolerated by the virus. These high levels of readthrough were achieved using a two-plasmid system, with Gag and Gag-Pol expressed from separate infectious clones. We also modulated readthrough by silencing expression of eukaryotic release factors 1 and 3 (eRF1 and eRF3) or by introducing aminoglycosides into the cells. The data obtained indicate that gammaretroviruses tolerate a substantial excess of viral Gag-Pol synthesis but are very sensitive to a reduction in levels of this polyprotein. Thus, as is also the case for ribosomal frameshifting, antiviral therapies targeting readthrough with inhibitory agents are likely to be the most beneficial. IMPORTANCE Many pathogenic RNA viruses and retroviruses use ribosomal frameshifting or stop codon readthrough to regulate expression of their replicase enzymes. These translational “recoding” processes are potential targets for antiviral intervention, but we have only a limited understanding of the consequences to virus replication of modulating the efficiency of recoding, particularly for those viruses employing readthrough. In this paper, we describe the first systematic analysis of the effect of increasing or decreasing readthrough efficiency on virus replication using the gammaretrovirus MuLV as a model system. We find unexpectedly that MuLV replication is only slightly inhibited by substantial increases in readthrough frequency, but as with other viruses that use recoding strategies, replication is quite sensitive to even modest reductions. These studies provide insights into both the readthrough process and MuLV replication and have implications for the selection of antivirals against gammaretroviruses.",2014 Sep,"['Csibra, Eszter', 'Brierley, Ian', 'Irigoyen, Nerea']",J Virol,,,True
c9931d8718e491e3002bbf42aec7cde49e93bac5,PMC,The unfolded protein response in virus infections,http://dx.doi.org/10.3389/fmicb.2014.00518,PMC4179733,25324837,CC BY,,2014 Sep 30,"Chan, Shiu-Wan",Front Microbiol,,,True
4f25223579f443edc058800f30c4fe8847a6ab57,PMC,Application of WHO’s guideline for the selection of sentinel sites for hospital-based influenza surveillance in Indonesia,http://dx.doi.org/10.1186/1472-6963-14-424,PMC4179842,25248619,CC BY,"BACKGROUND: A sentinel hospital-based severe acute respiratory infection (SARI) surveillance system was established in Indonesia in 2013. Deciding on the number, geographic location and hospitals to be selected as sentinel sites was a challenge. Based on the recently published WHO guideline for influenza surveillance (2012), this study presents the process for hospital sentinel site selection. METHODS: From the 2,165 hospitals in Indonesia, the first step was to shortlist to hospitals that had previously participated in respiratory disease surveillance systems and had acceptable surveillance performance history. The second step involved categorizing the shortlist according to five regions in Indonesia to maximize geographic representativeness. A checklist was developed based on the WHO recommended attributes for sentinel site selection including stability, feasibility, representativeness and the availability of data to enable disease burden estimation. Eight hospitals, a maximum of two per geographic region, were visited for checklist administration. Checklist findings from the eight hospitals were analyzed and sentinel sites selected in the third step. RESULTS: Six hospitals could be selected based on resources available to ensure system stability over a three-year period. For feasibility, all eight hospitals visited had mechanisms for specimen shipment and the capacity to report surveillance data, but two had limited motivation for system participation. For representativeness, the eight hospitals were geographically dispersed around Indonesia, and all could capture cases in all age and socio-economic groups. All eight hospitals had prerequisite population data to enable disease burden estimation. The two hospitals with low motivation were excluded and the remaining six were selected as sentinel sites. CONCLUSIONS: The multi-step process enabled sentinel site selection based on the WHO recommended attributes that emphasize right-sizing the surveillance system to ensure its stability and maximizing its geographic representativeness. This experience may guide other countries interested in adopting WHO’s influenza surveillance standards for sentinel site selection.",2014 Sep 23,"['Susilarini, Ni Ketut', 'Sitorus, Martahan', 'Praptaningsih, Catharina Yekti', 'Sampurno, Ondri Dwi', 'Bratasena, Arie', 'Mulyadi, Ester', 'Rusli, Roselinda', 'Fandil, Ahmad', 'Mangiri, Amalya', 'Apsari, Hana', 'Hariyanto, Edy', 'Samaan, Gina']",BMC Health Serv Res,,,True
db97b6fadbd7b65de3e513beec8f3eca89bac377,PMC,An evaluation of a liquid antimicrobial (Sal CURB®) for reducing the risk of porcine epidemic diarrhea virus infection of naïve pigs during consumption of contaminated feed,http://dx.doi.org/10.1186/s12917-014-0220-9,PMC4179854,25253192,CC BY,"BACKGROUND: Since its initial detection in May 2013, porcine epidemic diarrhea virus (PEDV) has spread rapidly throughout the US swine industry. Recently, contaminated feed was confirmed as a vehicle for PEDV infection of naïve piglets. This research provides in vivo data supporting the ability of a liquid antimicrobial product to reduce this risk. RESULTS: Sal CURB® (Kemin Industries, Des Moines, IA, USA) is a FDA-approved liquid antimicrobial used to control Salmonella contamination in poultry and swine diets. To test its effect against PEDV, Sal CURB®-treated feed was spiked with a stock isolate of PEDV (Ct = 25.22), which PEDV-naïve piglets were allowed to ingest via natural feeding behavior (ad libitum) for a 14-day period. For the purpose of a positive control, a separate group of piglets was allowed to ingest non-treated (Sal CURB®-free) feed also spiked with stock PEDV (Ct = 25.22). A negative control group received PEDV-free feed. Clinical signs of PEDV infection (vomiting and diarrhea) and viral shedding in feces were observed in the positive control group 2–3 days post-consumption of non-treated feed. In contrast, no evidence of infection was observed in pigs fed Sal CURB®-treated feed or in the negative controls throughout the 14-day study period. In addition, the Sal CURB®-treated feed samples had higher (p < 0.0001) mean PEDV Ct values than samples from the positive control group. CONCLUSIONS: These data provide proof of concept that feed treated with Sal CURB® can serve as a means to reduce the risk of PEDV infection through contaminated feed. Furthermore, the results from the positive control group provide additional proof of concept regarding the ability of contaminated feed to serve as a risk factor for PEDV infection of naïve piglets.",2014 Sep 25,"['Dee, Scott', 'Neill, Casey', 'Clement, Travis', 'Christopher-Hennings, Jane', 'Nelson, Eric']",BMC Vet Res,,,True
db0f13123f5ba69c4a2b52b2d87fb2f5cd350c3c,PMC,Comparison of Antibodies Hydrolyzing Myelin Basic Protein from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis,http://dx.doi.org/10.1371/journal.pone.0107807,PMC4180057,25265393,CC BY,"It was found that antibodies (Abs) against myelin basic protein (MBP) are the major components of the antibody response in multiple sclerosis (MS) patients. We have recently shown that IgGs from sera of MS patients are active in the hydrolysis of MBP. However, in literature there are no available data concerning possible MBP-hydrolyzing Abs in cerebrospinal fluid (CSF) of MS patients. We have shown that the average content of IgGs in their sera is about 195-fold higher than that in their CSF. Here we have compared, for the first time, the average content of lambda- and kappa-IgGs as well as IgGs of four different subclasses (IgG1-IgG4) in CSF and sera of MS patients. The average relative content of lambda-IgGs and kappa –IgGs in the case of CSFs (8.0 and 92.0%) and sera (12.3 and 87.7%) are comparable, while IgG1, IgG2, IgG3, and IgG4: CSF - 40.4, 49.0, 8.2, and 2.5% of total IgGs, respectively and the sera - 53.6, 36.0, 5.6, and 4.8%, decreased in different order. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF efficiently hydrolyze MBP and that their average specific catalytic activity is unpredictably ∼54-fold higher than that of Abs from sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that anti-MBP abzymes of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development.",2014 Sep 29,"['Doronin, Visilii B.', 'Parkhomenko, Taisiya A.', 'Castellazzi, Massimiliano', 'Padroni, Marina', 'Pastore, Michela', 'Buneva, Valentina N.', 'Granieri, Enrico', 'Nevinsky, Georgy A.']",PLoS One,,,True
a286d1120f3b36b22f1b9e4e6409cad9b8471370,PMC,Recognizing flu-like symptoms from videos,http://dx.doi.org/10.1186/1471-2105-15-300,PMC4180141,25217118,CC BY,"BACKGROUND: Vision-based surveillance and monitoring is a potential alternative for early detection of respiratory disease outbreaks in urban areas complementing molecular diagnostics and hospital and doctor visit-based alert systems. Visible actions representing typical flu-like symptoms include sneeze and cough that are associated with changing patterns of hand to head distances, among others. The technical difficulties lie in the high complexity and large variation of those actions as well as numerous similar background actions such as scratching head, cell phone use, eating, drinking and so on. RESULTS: In this paper, we make a first attempt at the challenging problem of recognizing flu-like symptoms from videos. Since there was no related dataset available, we created a new public health dataset for action recognition that includes two major flu-like symptom related actions (sneeze and cough) and a number of background actions. We also developed a suitable novel algorithm by introducing two types of Action Matching Kernels, where both types aim to integrate two aspects of local features, namely the space-time layout and the Bag-of-Words representations. In particular, we show that the Pyramid Match Kernel and Spatial Pyramid Matching are both special cases of our proposed kernels. Besides experimenting on standard testbed, the proposed algorithm is evaluated also on the new sneeze and cough set. Empirically, we observe that our approach achieves competitive performance compared to the state-of-the-arts, while recognition on the new public health dataset is shown to be a non-trivial task even with simple single person unobstructed view. CONCLUSIONS: Our sneeze and cough video dataset and newly developed action recognition algorithm is the first of its kind and aims to kick-start the field of action recognition of flu-like symptoms from videos. It will be challenging but necessary in future developments to consider more complex real-life scenario of detecting these actions simultaneously from multiple persons in possibly crowded environments.",2014 Sep 12,"['Thi, Tuan Hue', 'Wang, Li', 'Ye, Ning', 'Zhang, Jian', 'Maurer-Stroh, Sebastian', 'Cheng, Li']",BMC Bioinformatics,,,True
36ac477a0485cd6f631502a5fe2e471db2210799,PMC,Procalcitonin guidance for reduction of antibiotic use in patients hospitalized with severe acute exacerbations of asthma: a randomized controlled study with 12-month follow-up,http://dx.doi.org/10.1186/s13054-014-0471-7,PMC4180966,25189222,CC BY,"INTRODUCTION: Patients with severe acute exacerbations of asthma often receive inappropriate antibiotic treatment. We aimed to determine whether serum procalcitonin (PCT) levels can effectively and safely reduce antibiotic exposure in patients experiencing exacerbations of asthma. METHODS: In this randomized controlled trial, a total of 216 patients requiring hospitalization for severe acute exacerbations of asthma were screened for eligibility to participate and 169 completed the 12-month follow-up visit. Patients were randomized to either PCT-guided (PCT group) or standard (control group) antimicrobial therapy. In the control group, patients received antibiotics according to the attending physician’s discretion; in the PCT group, patients received antibiotics according to an algorithm based on serum PCT levels. The primary end point was antibiotic exposure; secondary end points were clinical recovery, length of hospital stay, clinical and laboratory parameters, spirometry, number of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma. RESULTS: PCT guidance reduced antibiotic prescription (48.9% versus 87.8%, respectively; P < 0.001) and antibiotic exposure (relative risk, 0.56; 95% confidence interval, 0.44 to 0.70; P < 0.001) compared to standard therapy. There were no significant differences in clinical recovery, length of hospital stay or clinical, laboratory and spirometry outcomes in both groups. Number of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma were similar during the 12-month follow-up period. CONCLUSION: A PCT-guided strategy allows antibiotic exposure to be reduced in patients with severe acute exacerbation of asthma without apparent harm. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR-TRC-12002534 (registered 26 September 2012)",2014 Sep 5,"['Long, Wei', 'Li, Li-juan', 'Huang, Gao-zhong', 'Zhang, Xue-min', 'Zhang, Yi-cui', 'Tang, Jian-guo', 'Zhang, Yu', 'Lu, Gang']",Crit Care,,,True
2d315ee4d1e5819f972a999a7cc1a1c83a8993e5,PMC,Graph-distance distribution of the Boltzmann ensemble of RNA secondary structures,http://dx.doi.org/10.1186/1748-7188-9-19,PMC4181469,25285153,CC BY,"BACKGROUND: Large RNA molecules are often composed of multiple functional domains whose spatial arrangement strongly influences their function. Pre-mRNA splicing, for instance, relies on the spatial proximity of the splice junctions that can be separated by very long introns. Similar effects appear in the processing of RNA virus genomes. Albeit a crude measure, the distribution of spatial distances in thermodynamic equilibrium harbors useful information on the shape of the molecule that in turn can give insights into the interplay of its functional domains. RESULT: Spatial distance can be approximated by the graph-distance in RNA secondary structure. We show here that the equilibrium distribution of graph-distances between a fixed pair of nucleotides can be computed in polynomial time by means of dynamic programming. While a naïve implementation would yield recursions with a very high time complexity of O(n(6)D(5)) for sequence length n and D distinct distance values, it is possible to reduce this to O(n(4)) for practical applications in which predominantly small distances are of of interest. Further reductions, however, seem to be difficult. Therefore, we introduced sampling approaches that are much easier to implement. They are also theoretically favorable for several real-life applications, in particular since these primarily concern long-range interactions in very large RNA molecules. CONCLUSIONS: The graph-distance distribution can be computed using a dynamic programming approach. Although a crude approximation of reality, our initial results indicate that the graph-distance can be related to the smFRET data. The additional file and the software of our paper are available from http://www.rna.uni-jena.de/RNAgraphdist.html.",2014 Sep 11,"['Qin, Jing', 'Fricke, Markus', 'Marz, Manja', 'Stadler, Peter F', 'Backofen, Rolf']",Algorithms Mol Biol,,,True
be2fad939fdfc83bded3b06dee772e6479049f9e,PMC,Graph-distance distribution of the Boltzmann ensemble of RNA secondary structures,http://dx.doi.org/10.1186/1748-7188-9-19,PMC4181469,25285153,CC BY,"BACKGROUND: Large RNA molecules are often composed of multiple functional domains whose spatial arrangement strongly influences their function. Pre-mRNA splicing, for instance, relies on the spatial proximity of the splice junctions that can be separated by very long introns. Similar effects appear in the processing of RNA virus genomes. Albeit a crude measure, the distribution of spatial distances in thermodynamic equilibrium harbors useful information on the shape of the molecule that in turn can give insights into the interplay of its functional domains. RESULT: Spatial distance can be approximated by the graph-distance in RNA secondary structure. We show here that the equilibrium distribution of graph-distances between a fixed pair of nucleotides can be computed in polynomial time by means of dynamic programming. While a naïve implementation would yield recursions with a very high time complexity of O(n(6)D(5)) for sequence length n and D distinct distance values, it is possible to reduce this to O(n(4)) for practical applications in which predominantly small distances are of of interest. Further reductions, however, seem to be difficult. Therefore, we introduced sampling approaches that are much easier to implement. They are also theoretically favorable for several real-life applications, in particular since these primarily concern long-range interactions in very large RNA molecules. CONCLUSIONS: The graph-distance distribution can be computed using a dynamic programming approach. Although a crude approximation of reality, our initial results indicate that the graph-distance can be related to the smFRET data. The additional file and the software of our paper are available from http://www.rna.uni-jena.de/RNAgraphdist.html.",2014 Sep 11,"['Qin, Jing', 'Fricke, Markus', 'Marz, Manja', 'Stadler, Peter F', 'Backofen, Rolf']",Algorithms Mol Biol,,,True
8bcded9bf20651adee9df9dc56030291f0b881fb,PMC,Epidemiology of respiratory viral infections in children enrolled in a study of influenza vaccine effectiveness,http://dx.doi.org/10.1111/irv.12229,PMC4181477,24483149,CC BY,"BACKGROUND: Influenza-like illness (ILI) confers a high annual morbidity in young children. We report the epidemiology of ILIs in children who participated in an influenza vaccine effectiveness study during the 2010 Southern Hemisphere influenza season in Sydney, Australia. METHODS: Children aged 0·5–3 years were prospectively recruited from child care centres (CCCs). We classified them as fully vaccinated, partially vaccinated and unvaccinated according to their receipt of unadjuvanted vaccines containing influenza A (H1N1)pdm09. For 13 weeks commencing 30 July 2010, parents reported when their children developed an ILI (fever ≥37·8°C/feverishness plus ≥1 respiratory symptom) and collected nose and/or throat swabs for multiplex respiratory virus polymerase chain reaction (PCR) testing. Health impacts were assessed by telephone interview at enrolment and two weeks after each ILI. RESULTS: There were 124 ILIs reported in 105 of 381 enrolled children. Swabs were taken in 117 ILIs: 175 viruses were identified from 103 swabs. Adeno- and rhinoviruses were most frequently identified; 44% of swabs yielded multiple viruses. No virus was associated with more severe symptoms, although rhinovirus-related ILIs lasted longer. Nose swabs had a higher virus detection rate than throat swabs. Influenza-vaccinated children were 1·6 times (P = 0·001) more likely than unvaccinated children to have a non-influenza ILI. CONCLUSION: Adeno- and rhinoviruses were the most common viruses causing ILI. Swabs taken by parents are an effective method for sample collection. Influenza-like illness was more common in children vaccinated against influenza in this observational study, but prior health-seeking behaviour may have contributed to this difference.",2014 May 31,"['Dierig, Alexa', 'Heron, Leon G', 'Lambert, Stephen B', 'Yin, Jiehui Kevin', 'Leask, Julie', 'Chow, Maria Yui Kwan', 'Sloots, Theo P', 'Nissen, Michael D', 'Ridda, Iman', 'Booy, Robert']",Influenza Other Respir Viruses,,,True
66fb607e8ee0e7b13f1abaedf0ed42451c8924a2,PMC,"Epidemiology of human adenovirus and molecular characterization of human adenovirus 55 in China, 2009–2012",http://dx.doi.org/10.1111/irv.12232,PMC4181478,24467816,CC BY,"BACKGROUND: Human adenovirus 55 (HAdV-55) has caused recent outbreaks of acute respiratory disease (ARD) among adults and military trainees. The active surveillance for HAdV infections was sparse in China, and current knowledge on the HAdV-type distributions and its molecular evolution is lacking. OBJECTIVES: To acquire better understanding on the prevalence and molecular evolution of HAdV-55 strains in China, for an informed strategy for disease control and prevention. POPULATION/METHODS: Nasopharyngeal aspirates were collected from hospitalized children with ARTI in Chongqing during 2009–2012. The genotype of HAdV isolates were determined by sequencing the partial hexon and fiber genes. Whole genome sequences of HAdV-55 were obtained for molecular evolution analysis. RESULTS: About 191 (8·55%) HAdV were detected in 2234 children, including 92 (48·2%) with HAdV-7, 72 (37·7%) with HAdV-3, 6 (3·1%) with HAdV-55, 5 (2·6%) with HAdV-5, 4 (2·1%) with HAdV-1, 1 (0·5%) with HAdV-2, and 11(5·8%) with untyped HAdV. Four of these children developed pneumonia, two of whom were diagnosed with severe pneumonia and/or encephalopathy. HAdV-55 isolates clustered with HAdV-11 sequences based on the hexon gene and clustered with HAdV-14 sequences based on the fiber gene and the whole genome. The overall evolutionary rates of hexon gene, fiber gene, and whole genome of HAdV-55 were estimated at 6·2 × 10(−5) s/s/y, 8·0 × 10(−5) s/s/y, and 1·7 × 10(−5) s/s/y, respectively. CONCLUSIONS: This study suggested HAdV-55 as an emerging infectious disease pathogen has conserved genetic structure and is closely related to each other. Further molecular investigation based on HAdV-55 of wider origin might facilitate understanding its diversity, dissemination, and transmission in China.",2014 May 28,"['Lu, Qing-Bin', 'Tong, Yi-Gang', 'Wo, Ying', 'Wang, Hong-Yu', 'Liu, En-Mei', 'Gray, Gregory C', 'Liu, Wei', 'Cao, Wu-Chun']",Influenza Other Respir Viruses,,,True
d1861375d64fea0dd4e02843a049792058ce6140,PMC,A systematic review of studies on forecasting the dynamics of influenza outbreaks,http://dx.doi.org/10.1111/irv.12226,PMC4181479,24373466,CC BY,"Forecasting the dynamics of influenza outbreaks could be useful for decision-making regarding the allocation of public health resources. Reliable forecasts could also aid in the selection and implementation of interventions to reduce morbidity and mortality due to influenza illness. This paper reviews methods for influenza forecasting proposed during previous influenza outbreaks and those evaluated in hindsight. We discuss the various approaches, in addition to the variability in measures of accuracy and precision of predicted measures. PubMed and Google Scholar searches for articles on influenza forecasting retrieved sixteen studies that matched the study criteria. We focused on studies that aimed at forecasting influenza outbreaks at the local, regional, national, or global level. The selected studies spanned a wide range of regions including USA, Sweden, Hong Kong, Japan, Singapore, United Kingdom, Canada, France, and Cuba. The methods were also applied to forecast a single measure or multiple measures. Typical measures predicted included peak timing, peak height, daily/weekly case counts, and outbreak magnitude. Due to differences in measures used to assess accuracy, a single estimate of predictive error for each of the measures was difficult to obtain. However, collectively, the results suggest that these diverse approaches to influenza forecasting are capable of capturing specific outbreak measures with some degree of accuracy given reliable data and correct disease assumptions. Nonetheless, several of these approaches need to be evaluated and their performance quantified in real-time predictions.",2014 May 23,"['Nsoesie, Elaine O', 'Brownstein, John S', 'Ramakrishnan, Naren', 'Marathe, Madhav V']",Influenza Other Respir Viruses,,,True
9543d56a69a743e9472e1955f27bfa935ae43942,PMC,Impact of 2009 pandemic influenza among Vietnamese children based on a population-based prospective surveillance from 2007 to 2011,http://dx.doi.org/10.1111/irv.12244,PMC4181797,24602158,CC BY,"BACKGROUND: Influenza virus is one of the major viral pathogens causing pediatric acute respiratory infection (ARI). The spread of pandemic influenza A (A(H1N1)pdm09) in 2009 around the globe had a huge impact on global health. OBJECTIVE: To investigate the impact of A(H1N1)pdm09 on pediatric ARI in Vietnam. STUDY DESIGN: An ongoing population-based prospective surveillance in central Vietnam was used. All children aged <15 years residing in Nha Trang city, enrolled to the ARI surveillance in Khanh Hoa General Hospital, from February 2007 through March 2011 were studied. Clinical data and nasopharyngeal swab samples were collected. Influenza A was detected and genotyped by multiplex polymerase chain reaction assays and sequencing. RESULTS: Among enrolled 2736 hospitalized ARI cases, 354 (13%) were positive for influenza A. Genotyping results revealed that seasonal H3N2 and H1N1 (sea-H1N1) viruses were cocirculating before A(H1N1)pdm09 appeared in July 2009. The A(H1N1)pdm09 replaced the sea-H1N1 after the pandemic. The majority of influenza A cases (90%) were aged <5 years with incidence rate of 537 (387–775) per 100 000 population. Annual incidence rates of hospitalized influenza cases for pre-, initial and post-pandemic periods among children aged <5 year were 474, 452, and 387 per 100 000, respectively. Children with A(H1N1)pdm09 were elder, visited the hospital earlier, less frequently had severe signs, and were less frequently associated with viral coinfection compared with seasonal influenza cases. CONCLUSIONS: The A(H1N1)pdm09 did not increase the influenza annual hospitalization incidence or disease severity compared with seasonal influenza among pediatric ARI cases in central Vietnam.",2014 Jul 7,"['Le, Minh Nhat', 'Yoshida, Lay Myint', 'Suzuki, Motoi', 'Nguyen, Hien Anh', 'Le, Huu Tho', 'Moriuchi, Hiroyuki', 'Dang, Duc Anh', 'Ariyoshi, Koya']",Influenza Other Respir Viruses,,,True
ef5fe7296ec8baf90d974cf5737af0da3ed403ea,PMC,"A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China",http://dx.doi.org/10.1111/irv.12257,PMC4181804,24828783,CC BY,"BACKGROUND: The epidemiology of local viral etiologies is essential for the management of viral respiratory tract infections. Limited data are available in China to describe the epidemiology of viral respiratory infections, especially in small–medium cities and rural areas. OBJECTIVES: To determine the viral etiology and seasonality of acute respiratory infections in hospitalized children, a 3-year study was conducted in Shenzhen, China. METHODS: Nasopharyngeal aspirates from eligible children were collected. Influenza and other respiratory viruses were tested by molecular assays simultaneously. Data were analyzed to describe the frequency and seasonality. RESULTS: Of the 2025 children enrolled in the study, 971 (48·0%) were positive for at least one viral pathogen, in which 890 (91·7%) were <4 years of age. The three most prevalent viruses were influenza A (IAV; 35·8%), respiratory syncytial virus (RSV; 30·5%) and human rhinovirus (HRV; 21·5%). Co-infections were found in 302 cases (31·1%), and dual viral infection was dominant. RSV, HRV and IAV were the most frequent viral agents involved in co-infection. On the whole, the obvious seasonal peaks mainly from March to May were observed with peak strength varying from 1 year to another. CONCLUSIONS: This study provides a basic profile of the epidemiology of acute respiratory viral infection in hospitalized children in Shenzhen. The spectrum of viruses in the study site is similar to that in other places, but the seasonality is closely related to geographic position, different from that in big cities in northern China and neighboring Hong Kong.",2014 Jul 14,"['He, Ying', 'Lin, Guang-Yu', 'Wang, Qiong', 'Cai, Xiao-Ying', 'Zhang, Yin-Hui', 'Lin, Chuang-Xing', 'Lu, Chang-Dong', 'Lu, Xue-Dong']",Influenza Other Respir Viruses,,,True
59914aa651a598b95b58825690eeb4477c7777ef,PMC,Impact of preceding respiratory viral infections on the clinical severity of patients with pneumococcal pneumonia,http://dx.doi.org/10.1111/irv.12265,PMC4181819,24962523,CC BY,"BACKGROUND: This study aimed to investigate the impact of preceding respiratory viral infections (RVI) on the clinical severity of pneumococcal pneumonia patients. METHODS: A retrospective observational study was conducted at a university hospital from January 2009 to March 2013. Study subjects included adults (aged ≥18 years) with pneumococcal pneumonia who had undergone laboratory tests for RVI. Multivariate logistic regression analysis was performed to identify risk factors associated with severe pneumococcal pneumonia, defined as severity with the Pneumonia Severity Index (PSI) score ≥91. RESULTS: In total, 191 patients with pneumococcal pneumonia were included for analysis and stratified into 2 groups: the severe group with a PSI score ≥91 (n = 99) and the non-severe group with a PSI score <91 (n = 92). Preceding RVIs were detected in 48 patients, including influenza A virus (n = 20), influenza B virus (n = 4), parainfluenza viruses (n = 5), metapneumovirus (n = 4), rhinovirus (n = 4), respiratory syncytial viruses (n = 6), coronaviruses (n = 2), and mixed viral infections (n = 3). In the multivariate logistic regression analysis, preceding RVIs (odds ratio [OR], 2·49; 95% confidence interval [CI], 1·10–5·60), male sex (OR, 2·58; 95% CI, 1·24–5·38), old age (OR, 2·92; 95% CI, 1·37–6·24), hypoalbuminemia (OR, 3·26; 95% CI, 1·56–6·84)], and azotemia (OR, 2·24; 95% CI, 1·08–4·67) were significantly associated with severe pneumococcal pneumonia. CONCLUSION: This study suggests that preceding RVIs might be one of the risk factors affecting the clinical severity of pneumococcal pneumonia.",2014 Sep 24,"['Yoon, Young Kyung', 'Yang, Kyung Sook', 'Sohn, Jang Wook', 'Lee, Chang Kyu', 'Kim, Min Ja']",Influenza Other Respir Viruses,,,True
3ddbaa41fdf3c15e1677fd5cbc0a7d6c7f1e51fc,PMC,Heat inactivation of the Middle East respiratory syndrome coronavirus,http://dx.doi.org/10.1111/irv.12261,PMC4181824,25074677,CC BY,"The culture supernatants of the emerging Middle East respiratory syndrome coronavirus (MERS-CoV) were submitted to three temperatures over time and tested for infectivity by TCID(50) method on Vero E6 cells. At 56°C, almost 25 minutes were necessary to reduce the initial titre by 4 log(10). Increasing temperature to 65°C had a strong negative effect on viral infectivity as virucidy dropped significantly to 1 minute. On the contrary, no significant decrease in titre was observed after 2 hours at 25°C. These data might be useful in establishing biosafety measures in laboratories against MERS-CoV.",2014 Sep 24,"['Leclercq, India', 'Batéjat, Christophe', 'Burguière, Ana M', 'Manuguerra, Jean-Claude']",Influenza Other Respir Viruses,,,True
47aa21ec26143c3b7a9ff3fa57eb20634cc41940,PMC,The Impact of “Omic” and Imaging Technologies on Assessing the Host Immune Response to Biodefence Agents,http://dx.doi.org/10.1155/2014/237043,PMC4182007,25333059,CC BY,"Understanding the interactions between host and pathogen is important for the development and assessment of medical countermeasures to infectious agents, including potential biodefence pathogens such as Bacillus anthracis, Ebola virus, and Francisella tularensis. This review focuses on technological advances which allow this interaction to be studied in much greater detail. Namely, the use of “omic” technologies (next generation sequencing, DNA, and protein microarrays) for dissecting the underlying host response to infection at the molecular level; optical imaging techniques (flow cytometry and fluorescence microscopy) for assessing cellular responses to infection; and biophotonic imaging for visualising the infectious disease process. All of these technologies hold great promise for important breakthroughs in the rational development of vaccines and therapeutics for biodefence agents.",2014 Sep 16,"['Tree, Julia A.', 'Flick-Smith, Helen', 'Elmore, Michael J.', 'Rowland, Caroline A.']",J Immunol Res,,,True
5721c27ac5defb5f651b26e7f45324c848212c06,PMC,Chimeric NP Non Coding Regions between Type A and C Influenza Viruses Reveal Their Role in Translation Regulation,http://dx.doi.org/10.1371/journal.pone.0109046,PMC4182659,25268971,CC BY,"Exchange of the non coding regions of the NP segment between type A and C influenza viruses was used to demonstrate the importance not only of the proximal panhandle, but also of the initial distal panhandle strength in type specificity. Both elements were found to be compulsory to rescue infectious virus by reverse genetics systems. Interestingly, in type A influenza virus infectious context, the length of the NP segment 5′ NC region once transcribed into mRNA was found to impact its translation, and the level of produced NP protein consequently affected the level of viral genome replication.",2014 Sep 30,"['Crescenzo-Chaigne, Bernadette', 'Barbezange, Cyril', 'Frigard, Vianney', 'Poulain, Damien', 'van der Werf, Sylvie']",PLoS One,,,True
865949791a49615aa67ae0444e5987348c82ba65,PMC,Identification of Host-Immune Response Protein Candidates in the Sera of Human Oral Squamous Cell Carcinoma Patients,http://dx.doi.org/10.1371/journal.pone.0109012,PMC4182798,25272005,CC BY,"One of the most common cancers worldwide is oral squamous cell carcinoma (OSCC), which is associated with a significant death rate and has been linked to several risk factors. Notably, failure to detect these neoplasms at an early stage represents a fundamental barrier to improving the survival and quality of life of OSCC patients. In the present study, serum samples from OSCC patients (n = 25) and healthy controls (n = 25) were subjected to two-dimensional gel electrophoresis (2-DE) and silver staining in order to identify biomarkers that might allow early diagnosis. In this regard, 2-DE spots corresponding to various up- and down-regulated proteins were sequenced via high-resolution MALDI-TOF mass spectrometry and analyzed using the MASCOT database. We identified the following differentially expressed host-specific proteins within sera from OSCC patients: leucine-rich α2-glycoprotein (LRG), alpha-1-B-glycoprotein (ABG), clusterin (CLU), PRO2044, haptoglobin (HAP), complement C3c (C3), proapolipoprotein A1 (proapo-A1), and retinol-binding protein 4 precursor (RBP4). Moreover, five non-host factors were detected, including bacterial antigens from Acinetobacter lwoffii, Burkholderia multivorans, Myxococcus xanthus, Laribacter hongkongensis, and Streptococcus salivarius. Subsequently, we analyzed the immunogenicity of these proteins using pooled sera from OSCC patients. In this regard, five of these candidate biomarkers were found to be immunoreactive: CLU, HAP, C3, proapo-A1 and RBP4. Taken together, our immunoproteomics approach has identified various serum biomarkers that could facilitate the development of early diagnostic tools for OSCC.",2014 Oct 1,"['Chen, Yeng', 'Azman, Siti Nuraishah', 'Kerishnan, Jesinda P.', 'Zain, Rosnah Binti', 'Chen, Yu Nieng', 'Wong, Yin-Ling', 'Gopinath, Subash C. B.']",PLoS One,,,True
8ba20a12c92103d82364b8abca49cfcd91d91c13,PMC,N-glycan Cryptic Antigens as Active Immunological Targets in Prostate Cancer Patients,http://dx.doi.org/10.4172/jpb.1000218,PMC4183219,25284963,CC BY,"Although tumor-associated abnormal glycosylation has been recognized for decades, information regarding host recognition of the evolving tumor glycome remains elusive. We report here a carbohydrate microarray analysis of a number of tumor-associated carbohydrates for their serum antibody reactivities and potential immunogenicity in humans. These are the precursors, cores and internal sequences of N-glycans. They are usually masked by other sugar moieties and belong to a class of glyco-antigens that are normally “cryptic”. However, viral expression of these carbohydrates may trigger host immune responses. For examples, HIV-1 and SARS-CoV display Man9 clusters and tri- or multi-antennary type II (Galβ1→4GlcNAc) chains (Tri/m-II), respectively; viral neutralizing antibodies often target these sugar moieties. We asked, therefore, whether prostate tumor expression of corresponding carbohydrates triggers antibody responses in vivo. Using carbohydrate microarrays, we analyzed a panel of human sera, including 17 samples from prostate cancer patients and 12 from men with Benign Prostatic Hyperplasia (BPH). We observed that IgG antibodies targeting the Man9- or Tri-/m-II-autoantigens are readily detectable in the sera of men with BPH, as well as those with cancer. Importantly, these antibody activities were selectively increased in prostate cancer patients. Thus, human immune systems actively recognize these N-glycan cryptic carbohydrates and produce targeting antibodies. This finding shads a light on a class of previously less studied immunological targets of human cancers. Identifying the diagnostic, prognostic and therapeutic values of these targets will require further investigation.",2012 Apr 30,"Wang, Denong",J Proteomics Bioinform,,,True
3abc03ade244048ff2dbe668caa5cb9cb61a19eb,PMC,N-glycan Cryptic Antigens as Active Immunological Targets in Prostate Cancer Patients,http://dx.doi.org/10.4172/jpb.1000218,PMC4183219,25284963,CC BY,"Although tumor-associated abnormal glycosylation has been recognized for decades, information regarding host recognition of the evolving tumor glycome remains elusive. We report here a carbohydrate microarray analysis of a number of tumor-associated carbohydrates for their serum antibody reactivities and potential immunogenicity in humans. These are the precursors, cores and internal sequences of N-glycans. They are usually masked by other sugar moieties and belong to a class of glyco-antigens that are normally “cryptic”. However, viral expression of these carbohydrates may trigger host immune responses. For examples, HIV-1 and SARS-CoV display Man9 clusters and tri- or multi-antennary type II (Galβ1→4GlcNAc) chains (Tri/m-II), respectively; viral neutralizing antibodies often target these sugar moieties. We asked, therefore, whether prostate tumor expression of corresponding carbohydrates triggers antibody responses in vivo. Using carbohydrate microarrays, we analyzed a panel of human sera, including 17 samples from prostate cancer patients and 12 from men with Benign Prostatic Hyperplasia (BPH). We observed that IgG antibodies targeting the Man9- or Tri-/m-II-autoantigens are readily detectable in the sera of men with BPH, as well as those with cancer. Importantly, these antibody activities were selectively increased in prostate cancer patients. Thus, human immune systems actively recognize these N-glycan cryptic carbohydrates and produce targeting antibodies. This finding shads a light on a class of previously less studied immunological targets of human cancers. Identifying the diagnostic, prognostic and therapeutic values of these targets will require further investigation.",2012 Apr 30,"Wang, Denong",J Proteomics Bioinform,,,False
05445d95af0648219e8eb051ab3015b2a4615027,PMC,Immune Biomarkers Predictive of Respiratory Viral Infection in Elderly Nursing Home Residents,http://dx.doi.org/10.1371/journal.pone.0108481,PMC4183538,25275464,CC BY,"OBJECTIVE: To determine if immune phenotypes associated with immunosenescence predict risk of respiratory viral infection in elderly nursing home residents. METHODS: Residents ≥65 years from 32 nursing homes in 4 Canadian cities were enrolled in Fall 2009, 2010 and 2011, and followed for one influenza season. Following influenza vaccination, peripheral blood mononuclear cells (PBMCs) were obtained and analysed by flow cytometry for T-regs, CD4+ and CD8+ T-cell subsets (CCR7+CD45RA+, CCR7-CD45RA+ and CD28-CD57+) and CMV-reactive CD4+ and CD8+ T-cells. Nasopharyngeal swabs were obtained and tested for viruses in symptomatic residents. A Cox proportional hazards model adjusted for age, sex and frailty, determined the relationship between immune phenotypes and time to viral infection. RESULTS: 1072 residents were enrolled; median age 86 years and 72% female. 269 swabs were obtained, 87 were positive for virus: influenza (24%), RSV (14%), coronavirus (32%), rhinovirus (17%), human metapneumovirus (9%) and parainfluenza (5%). In multivariable analysis, high T-reg% (HR 0.41, 95% CI 0.20–0.81) and high CMV-reactive CD4+ T-cell% (HR 1.69, 95% CI 1.03–2.78) were predictive of respiratory viral infection. CONCLUSIONS: In elderly nursing home residents, high CMV-reactive CD4+ T-cells were associated with an increased risk and high T-regs were associated with a reduced risk of respiratory viral infection.",2014 Oct 2,"['Johnstone, Jennie', 'Parsons, Robin', 'Botelho, Fernando', 'Millar, Jamie', 'McNeil, Shelly', 'Fulop, Tamas', 'McElhaney, Janet', 'Andrew, Melissa K.', 'Walter, Stephen D.', 'Devereaux, P. J.', 'Malekesmaeili, Mehrnoush', 'Brinkman, Ryan R.', 'Mahony, James', 'Bramson, Jonathan', 'Loeb, Mark']",PLoS One,,,True
97229e8af52b75aa9ac0f0eb530bf89f7f5ec134,PMC,Cyclophilin A Associates with Enterovirus-71 Virus Capsid and Plays an Essential Role in Viral Infection as an Uncoating Regulator,http://dx.doi.org/10.1371/journal.ppat.1004422,PMC4183573,25275585,CC BY,"Viruses utilize host factors for their efficient proliferation. By evaluating the inhibitory effects of compounds in our library, we identified inhibitors of cyclophilin A (CypA), a known immunosuppressor with peptidyl-prolyl cis-trans isomerase activity, can significantly attenuate EV71 proliferation. We demonstrated that CypA played an essential role in EV71 entry and that the RNA interference-mediated reduction of endogenous CypA expression led to decreased EV71 multiplication. We further revealed that CypA directly interacted with and modified the conformation of H-I loop of the VP1 protein in EV71 capsid, and thus regulated the uncoating process of EV71 entry step in a pH-dependent manner. Our results aid in the understanding of how host factors influence EV71 life cycle and provide new potential targets for developing antiviral agents against EV71 infection.",2014 Oct 2,"['Qing, Jie', 'Wang, Yaxin', 'Sun, Yuna', 'Huang, Jiaoyan', 'Yan, Wenzhong', 'Wang, Jinglan', 'Su, Dan', 'Ni, Cheng', 'Li, Jian', 'Rao, Zihe', 'Liu, Lei', 'Lou, Zhiyong']",PLoS Pathog,,,True
1542e8e707bd5fa1cb6b3919722fc30ced018c1f,PMC,Lack of a 5.9 kDa Peptide C-Terminal Fragment of Fibrinogen α Chain Precedes Fibrosis Progression in Patients with Liver Disease,http://dx.doi.org/10.1371/journal.pone.0109254,PMC4183580,25275549,CC BY,"Early detection of fibrosis progression is of major relevance for the diagnosis and management of patients with liver disease. This study was designed to find non-invasive biomarkers for fibrosis in a clinical context where this process occurs rapidly, HCV-positive patients who underwent liver transplantation (LT). We analyzed 93 LT patients with HCV recurrence, 41 non-LT patients with liver disease showing a fibrosis stage F≥1 and 9 patients without HCV recurrence who received antiviral treatment before LT, as control group. Blood obtained from 16 healthy subjects was also analyzed. Serum samples were fractionated by ion exchange chromatography and their proteomic profile was analyzed by SELDI-TOF-MS. Characterization of the peptide of interest was performed by ion chromatography and electrophoresis, followed by tandem mass spectrometry identification. Marked differences were observed between the serum proteome profile of LT patients with early fibrosis recurrence and non-recurrent LT patients. A robust peak intensity located at 5905 m/z was the distinguishing feature of non-recurrent LT patients. However, the same peak was barely detected in recurrent LT patients. Similar results were found when comparing samples of healthy subjects with those of non-LT fibrotic patients, indicating that our findings were not related to either LT or HCV infection. Using tandem mass-spectrometry, we identified the protein peak as a C-terminal fragment of the fibrinogen α chain. Cell culture experiments demonstrated that TGF-β reduces α-fibrinogen mRNA expression and 5905 m/z peak intensity in HepG2 cells, suggesting that TGF-β activity regulates the circulating levels of this protein fragment. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen α chain as an early serum biomarker of fibrogenic processes in patients with liver disease.",2014 Oct 2,"['Marfà, Santiago', 'Crespo, Gonzalo', 'Reichenbach, Vedrana', 'Forns, Xavier', 'Casals, Gregori', 'Morales-Ruiz, Manuel', 'Navasa, Miquel', 'Jiménez, Wladimiro']",PLoS One,,,True
b84e5b51b40b345b68445d68483cc478e9ce5beb,PMC,Characterization of Uncultivable Bat Influenza Virus Using a Replicative Synthetic Virus,http://dx.doi.org/10.1371/journal.ppat.1004420,PMC4183581,25275541,CC BY,"Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.",2014 Oct 2,"['Zhou, Bin', 'Ma, Jingjiao', 'Liu, Qinfang', 'Bawa, Bhupinder', 'Wang, Wei', 'Shabman, Reed S.', 'Duff, Michael', 'Lee, Jinhwa', 'Lang, Yuekun', 'Cao, Nan', 'Nagy, Abdou', 'Lin, Xudong', 'Stockwell, Timothy B.', 'Richt, Juergen A.', 'Wentworth, David E.', 'Ma, Wenjun']",PLoS Pathog,,,True
eb8769154d6a5a4a44f5cea8a1b92082f9c278a6,PMC,Nerve growth factor reduces amiloride‐sensitive Na(+) transport in human airway epithelial cells,http://dx.doi.org/10.14814/phy2.12073,PMC4187554,25347857,CC BY,"Nerve growth factor (NGF) is overexpressed in patients with inflammatory lung diseases, including virus infections. Airway surface liquid (ASL), which is regulated by epithelial cell ion transport, is essential for normal lung function. No information is available regarding the effect of NGF on ion transport of airway epithelium. To investigate whether NGF can affect ion transport, human primary air‐interface cultured epithelial cells were placed in Ussing chambers to obtain transepithelial voltage (−7.1 ± 3.4 mV), short‐circuit current (I(sc), 5.9 ± 1.0 μA), and transepithelial resistance (750 Ω·cm(2)), and to measure responses to ion transport inhibitors. Amiloride (apical, 3.5 × 10(−5) mol/L) decreased I(sc) by 55.3%. Apically applied NGF (1 ng/mL) reduced I(sc) by 5.3% in 5 min; basolaterally applied NGF had no effect. The response to amiloride was reduced (41.6%) in the presence of NGF. K‐252a (10 nmol/L, apical) did not itself affect Na(+) transport, but it attenuated the NGF‐induced reduction in Na(+) transport, indicating the participation of the trkA receptor in the NGF‐induced reduction in Na(+) transport. PD‐98059 (30 μmol/L, apical and basolateral) did not itself affect Na(+) transport, but attenuated the NGF‐induced reduction in Na(+) transport, indicating that trkA activated the Erk 1/2 signaling cascade. NGF stimulated phosphorylation of Erk 1/2 and the β‐subunit of ENaC. K‐252a and PD‐98059 inhibited these responses. NGF had no effect on I(sc) in the presence of apical nystatin (50 μmol/L). These results indicate that NGF inhibits Na(+) transport through a trkA‐Erk 1/2‐activated signaling pathway linked to ENaC phosphorylation.",2014 Jul 17,"['Shimko, Michael J.', 'Zaccone, Eric J.', 'Thompson, Janet A.', 'Schwegler‐Berry, Diane', 'Kashon, Michael L.', 'Fedan, Jeffrey S.']",Physiol Rep,,,True
d7817865765ddf7b0e1635e74b7a9393d0979a66,PMC,Visualization of a substrate-induced productive conformation of the catalytic triad of the Neisseria meningitidis peptidoglycan O-acetylesterase reveals mechanistic conservation in SGNH esterase family members,http://dx.doi.org/10.1107/S1399004714016770,PMC4188005,25286847,CC BY,"Peptidoglycan O-acetylesterase (Ape1), which is required for host survival in Neisseria sp., belongs to the diverse SGNH hydrolase superfamily, which includes important viral and bacterial virulence factors. Here, multi-domain crystal structures of Ape1 with an SGNH catalytic domain and a newly identified putative peptidoglycan-detection module are reported. Enzyme catalysis was performed in Ape1 crystals and key catalytic intermediates along the SGNH esterase hydrolysis reaction pathway were visualized, revealing a substrate-induced productive conformation of the catalytic triad, a mechanistic detail that has not previously been observed. This substrate-induced productive conformation of the catalytic triad shifts the established dogma on these enzymes, generating valuable insight into the structure-based design of drugs targeting the SGNH esterase superfamily.",2014 Sep 27,"['Williams, Allison H.', 'Veyrier, Frédéric J.', 'Bonis, Mathilde', 'Michaud, Yann', 'Raynal, Bertrand', 'Taha, Muhamed-Kheir', 'White, Stephen W.', 'Haouz, Ahmed', 'Boneca, Ivo G.']",Acta Crystallogr D Biol Crystallogr,,,True
56f4b284986e2ede2a15c810ad7b342cbfcc1fd6,PMC,Visualization of a substrate-induced productive conformation of the catalytic triad of the Neisseria meningitidis peptidoglycan O-acetylesterase reveals mechanistic conservation in SGNH esterase family members,http://dx.doi.org/10.1107/S1399004714016770,PMC4188005,25286847,CC BY,"Peptidoglycan O-acetylesterase (Ape1), which is required for host survival in Neisseria sp., belongs to the diverse SGNH hydrolase superfamily, which includes important viral and bacterial virulence factors. Here, multi-domain crystal structures of Ape1 with an SGNH catalytic domain and a newly identified putative peptidoglycan-detection module are reported. Enzyme catalysis was performed in Ape1 crystals and key catalytic intermediates along the SGNH esterase hydrolysis reaction pathway were visualized, revealing a substrate-induced productive conformation of the catalytic triad, a mechanistic detail that has not previously been observed. This substrate-induced productive conformation of the catalytic triad shifts the established dogma on these enzymes, generating valuable insight into the structure-based design of drugs targeting the SGNH esterase superfamily.",2014 Sep 27,"['Williams, Allison H.', 'Veyrier, Frédéric J.', 'Bonis, Mathilde', 'Michaud, Yann', 'Raynal, Bertrand', 'Taha, Muhamed-Kheir', 'White, Stephen W.', 'Haouz, Ahmed', 'Boneca, Ivo G.']",Acta Crystallogr D Biol Crystallogr,,,False
1469710f9b5dce0601307791210b86a225dd1be1,PMC,Unusual Influenza A Viruses in Bats,http://dx.doi.org/10.3390/v6093438,PMC4189031,25256392,CC BY,"Influenza A viruses infect a remarkably diverse number of hosts. Two completely new influenza A virus subtypes were recently discovered in bats, dramatically expanding the host range of the virus. These bat viruses are extremely divergent from all other known strains and likely have unique replication cycles. Phylogenetic analysis indicates long-term, isolated evolution in bats. This is supported by a high seroprevalence in sampled bat populations. As bats represent ~20% of all classified mammals, these findings suggests the presence of a massive cryptic reservoir of poorly characterized influenza A viruses. Here, we review the exciting progress made on understanding these newly discovered viruses, and discuss their zoonotic potential.",2014 Sep 17,"Mehle, Andrew",Viruses,,,True
2fd379bd7d8ce15f444b2fa608e6c5899441d52a,PMC,IFITM Proteins Inhibit Entry Driven by the MERS-Coronavirus Spike Protein: Evidence for Cholesterol-Independent Mechanisms,http://dx.doi.org/10.3390/v6093683,PMC4189045,25256397,CC BY,"The interferon-inducible transmembrane (IFITM) proteins 1, 2 and 3 inhibit the host cell entry of several enveloped viruses, potentially by promoting the accumulation of cholesterol in endosomal compartments. IFITM3 is essential for control of influenza virus infection in mice and humans. In contrast, the role of IFITM proteins in coronavirus infection is less well defined. Employing a retroviral vector system for analysis of coronavirus entry, we investigated the susceptibility of human-adapted and emerging coronaviruses to inhibition by IFITM proteins. We found that entry of the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is sensitive to inhibition by IFITM proteins. In 293T cells, IFITM-mediated inhibition of cellular entry of the emerging MERS- and SARS-CoV was less efficient than blockade of entry of the globally circulating human coronaviruses 229E and NL63. Similar differences were not observed in A549 cells, suggesting that cellular context and/or IFITM expression levels can impact inhibition efficiency. The differential IFITM-sensitivity of coronaviruses observed in 293T cells afforded the opportunity to investigate whether efficiency of entry inhibition by IFITMs and endosomal cholesterol accumulation correlate. No such correlation was observed. Furthermore, entry mediated by the influenza virus hemagglutinin was robustly inhibited by IFITM3 but was insensitive to accumulation of endosomal cholesterol, indicating that modulation of cholesterol synthesis/transport did not account for the antiviral activity of IFITM3. Collectively, these results show that the emerging MERS-CoV is a target of the antiviral activity of IFITM proteins and demonstrate that mechanisms other than accumulation of endosomal cholesterol can contribute to viral entry inhibition by IFITMs.",2014 Sep 26,"['Wrensch, Florian', 'Winkler, Michael', 'Pöhlmann, Stefan']",Viruses,,,True
d8271398b9073fbb1ad449e72697e6ae8f71d3d8,PMC,Passive Broad-Spectrum Influenza Immunoprophylaxis,http://dx.doi.org/10.1155/2014/267594,PMC4190013,25328697,CC BY,"Influenza is a perennial problem affecting millions of people annually with the everpresent threat of devastating pandemics. Active prophylaxis by vaccination against influenza virus is currently the main countermeasure supplemented with antivirals. However, disadvantages of this strategy include the impact of antigenic drift, necessitating constant updating of vaccine strain composition, and emerging antiviral drug resistance. The development of other options for influenza prophylaxis, particularly with broad acting agents able to provide protection in the period between the onset of a pandemic and the development of a strain specific vaccine, is of great interest. Exploitation of broad-spectrum mediators could provide barricade protection in the early critical phase of influenza virus outbreaks. Passive immunity has the potential to provide immediate antiviral effects, inhibiting virus replication, reducing virus shedding, and thereby protecting vulnerable populations in the event of an impending influenza pandemic. Here, we review passive broad-spectrum influenza prophylaxis options with a focus on harnessing natural host defenses, including interferons and antibodies.",2014 Sep 22,"['Berry, Cassandra M.', 'Penhale, William J.', 'Sangster, Mark Y.']",Influenza Res Treat,,,True
f5df82125769765004c7dd11f066688e6dc3cc76,PMC,Regulation of TGF-β Signal Transduction,http://dx.doi.org/10.1155/2014/874065,PMC4190275,25332839,CC BY,"Transforming growth factor-β (TGF-β) signaling regulates diverse cellular processes, including cell proliferation, differentiation, apoptosis, cell plasticity, and migration. TGF-β signaling can be mediated by Smad proteins or other signaling proteins such as MAP kinases and Akt. TGF-β signaling is tightly regulated at different levels along the pathways to ensure its proper physiological functions in different cells and tissues. Deregulation of TGF-β signaling has been associated with various kinds of diseases, such as cancer and tissue fibrosis. This paper focuses on our recent work on regulation of TGF-β signaling.",2014 Sep 23,"['Zhao, Bing', 'Chen, Ye-Guang']",Scientifica (Cairo),,,True
19e9c8796df362aa81ecfabf7730cfa4df5e5be6,PMC,Establishment of Myotis myotis Cell Lines - Model for Investigation of Host-Pathogen Interaction in a Natural Host for Emerging Viruses,http://dx.doi.org/10.1371/journal.pone.0109795,PMC4190323,25295526,CC BY,"Bats are found to be the natural reservoirs for many emerging viruses. In most cases, severe clinical signs caused by such virus infections are normally not seen in bats. This indicates differences in the virus-host interactions and underlines the necessity to develop natural host related models to study these phenomena. Due to the strict protection of European bat species, immortalized cell lines are the only alternative to investigate the innate anti-virus immune mechanisms. Here, we report about the establishment and functional characterization of Myotis myotis derived cell lines from different tissues: brain (MmBr), tonsil (MmTo), peritoneal cavity (MmPca), nasal epithelium (MmNep) and nervus olfactorius (MmNol) after immortalization by SV 40 large T antigen. The usefulness of these cell lines to study antiviral responses has been confirmed by analysis of their susceptibility to lyssavirus infection and the mRNA patterns of immune-relevant genes after poly I:C stimulation. Performed experiments indicated varying susceptibility to lyssavirus infection with MmBr being considerably less susceptible than the other cell lines. Further investigation demonstrated a strong activation of interferon mediated antiviral response in MmBr contributing to its resistance. The pattern recognition receptors: RIG-I and MDA5 were highly up-regulated during rabies virus infection in MmBr, suggesting their involvement in promotion of antiviral responses. The presence of CD14 and CD68 in MmBr suggested MmBr cells are microglia-like cells which play a key role in host defense against infections in the central nervous system (CNS). Thus the expression pattern of MmBr combined with the observed limitation of lyssavirus replication underpin a protective mechanism of the CNS controlling the lyssavirus infection. Overall, the established cell lines are important tools to analyze antiviral innate immunity in M. myotis against neurotropic virus infections and present a valuable tool for a broad spectrum of future investigations in cellular biology of M. myotis.",2014 Oct 8,"['He, Xiaocui', 'Korytář, Tomáš', 'Zhu, Yaqing', 'Pikula, Jiří', 'Bandouchova, Hana', 'Zukal, Jan', 'Köllner, Bernd']",PLoS One,,,True
7a6456acf2a0eda491acf31d4887daf43a25ca27,PMC,"Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses",http://dx.doi.org/10.1186/1743-422X-11-170,PMC4190492,25253051,CC BY,"BACKGROUND: The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. FINDINGS: The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decreased. Both the H1N1 and H1N2 infected pigs lacked gross lesions at PID 2, but they showed moderate to severe pneumonia on PID 4, 7 and 14. The pigs infected with H1N1 had significant scores of gross and histopathological lesions when compared with the other pigs infected with H1N2, H3N2, and mock at PID 14. Mean SIV antigen-positive scores were rarely detected for pigs infected with H1N2 and H3N2 from PID 7, whereas a significantly increased amount of viral antigens were found in the bronchioles and alveolar epithelium of the H1N1infected pigs at PID 14. CONCLUSIONS: We demonstrated that Korean SIV subtypes had different pulmonary pathologic patterns. The Korean H3N2 rapidly induced acute lung lesions such as broncho-interstitial pneumonia, while the Korean H1N1 showed longer course of infection as compared to other strains.",2014 Sep 24,"['Lyoo, Kwang-Soo', 'Kim, Jeong-Ki', 'Jung, Kwonil', 'Kang, Bo-Kyu', 'Song, Daesub']",Virol J,,,True
aa14d6de32495ec579e30a5c6f1ae21666c01c8a,PMC,Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives,http://dx.doi.org/10.3390/pharmaceutics6030378,PMC4190526,25014738,CC BY,"Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents.",2014 Jul 10,"['Xu, Yingying', 'Yuen, Pak-Wai', 'Lam, Jenny Ka-Wing']",Pharmaceutics,,,True
7be0bfff671903d1176a2da34f16f1ff8189b554,PMC,The methyltransferase domain of dengue virus protein NS5 ensures efficient RNA synthesis initiation and elongation by the polymerase domain,http://dx.doi.org/10.1093/nar/gku666,PMC4191377,25209234,CC BY,"Viral RNA-dependent RNA polymerases (RdRps) responsible for the replication of single-strand RNA virus genomes exert their function in the context of complex replication machineries. Within these replication complexes the polymerase activity is often highly regulated by RNA elements, proteins or other domains of multi-domain polymerases. Here, we present data of the influence of the methyltransferase domain (NS5-MTase) of dengue virus (DENV) protein NS5 on the RdRp activity of the polymerase domain (NS5-Pol). The steady-state polymerase activities of DENV-2 recombinant NS5 and NS5-Pol are compared using different biochemical assays allowing the dissection of the de novo initiation, transition and elongation steps of RNA synthesis. We show that NS5-MTase ensures efficient RdRp activity by stimulating the de novo initiation and the elongation phase. This stimulation is related to a higher affinity of NS5 toward the single-strand RNA template indicating NS5-MTase either completes a high-affinity RNA binding site and/or promotes the correct formation of the template tunnel. Furthermore, the NS5-MTase increases the affinity of the priming nucleotide ATP upon de novo initiation and causes a higher catalytic efficiency of the polymerase upon elongation. The complex stimulation pattern is discussed under the perspective that NS5 adopts several conformations during RNA synthesis.",2014 Oct 13,"['Potisopon, Supanee', 'Priet, Stéphane', 'Collet, Axelle', 'Decroly, Etienne', 'Canard, Bruno', 'Selisko, Barbara']",Nucleic Acids Res,,,True
d307fc598aa1ad8f3c3480d20a996a23698cb57d,PMC,The methyltransferase domain of dengue virus protein NS5 ensures efficient RNA synthesis initiation and elongation by the polymerase domain,http://dx.doi.org/10.1093/nar/gku666,PMC4191377,25209234,CC BY,"Viral RNA-dependent RNA polymerases (RdRps) responsible for the replication of single-strand RNA virus genomes exert their function in the context of complex replication machineries. Within these replication complexes the polymerase activity is often highly regulated by RNA elements, proteins or other domains of multi-domain polymerases. Here, we present data of the influence of the methyltransferase domain (NS5-MTase) of dengue virus (DENV) protein NS5 on the RdRp activity of the polymerase domain (NS5-Pol). The steady-state polymerase activities of DENV-2 recombinant NS5 and NS5-Pol are compared using different biochemical assays allowing the dissection of the de novo initiation, transition and elongation steps of RNA synthesis. We show that NS5-MTase ensures efficient RdRp activity by stimulating the de novo initiation and the elongation phase. This stimulation is related to a higher affinity of NS5 toward the single-strand RNA template indicating NS5-MTase either completes a high-affinity RNA binding site and/or promotes the correct formation of the template tunnel. Furthermore, the NS5-MTase increases the affinity of the priming nucleotide ATP upon de novo initiation and causes a higher catalytic efficiency of the polymerase upon elongation. The complex stimulation pattern is discussed under the perspective that NS5 adopts several conformations during RNA synthesis.",2014 Oct 13,"['Potisopon, Supanee', 'Priet, Stéphane', 'Collet, Axelle', 'Decroly, Etienne', 'Canard, Bruno', 'Selisko, Barbara']",Nucleic Acids Res,,,False
51e10bb6f0ef0363cab568d94c52db244ce7ad1f,PMC,"Seasonal Variation of Newly Notified Pulmonary Tuberculosis Cases from 2004 to 2013 in Wuhan, China",http://dx.doi.org/10.1371/journal.pone.0108369,PMC4193739,25303675,CC BY,"BACKGROUND: Although there was a report about the seasonal variation in Wuhan city, it only analyzed the prevalence data of pulmonary tuberculosis (TB) cases, and just studied the seasonality by subgroup of smear positive and negative from 2006 to 2010 by spectral analysis. In this study, we investigated the seasonality of the total newly notified pulmonary TB cases by subgroups such as time period, sex, age, occupation, district, and sputum smear result from 2004 to 2013 in Wuhan by a popular seasonal adjustment model (TRAMO-SEATS). METHODS: Monthly pulmonary TB cases from 2004 to 2013 in Wuhan were analyzed by the TRAMO-SEATS seasonal adjustment program. Seasonal amplitude was calculated and compared within the subgroups. RESULTS: From 2004 to 2013, there were 77.76 thousand newly notified pulmonary TB cases in Wuhan, China. There was a dominant peak spring peak (March) with seasonal amplitude of 56.81% and a second summer peak (September) of 43.40%, compared with the trough month (December). The spring seasonal amplitude in 2004–2008 was higher than that of 2009–2013(P<0.05). There were no statistical differences for spring seasonal amplitude within subgroups of gender, age, district, and sputum smear result (P>0.05). However, there were significant differences in spring seasonal amplitude by occupation, with amplitude ranging from 59.37% to 113.22% (P<0.05). The summer seasonal amplitude in 2004–2008 was higher than that of 2009–2013(P<0.05). There were no statistical differences in summer seasonal amplitude within subgroups of gender, district, sputum smear result(P>0.05). There were significant differences in summer seasonal amplitude by age, with amplitude ranging from 36.05% to 100.09% (P<0.05). Also, there were significant differences in summer seasonal amplitude by occupation, with amplitude ranging from 43.40% to 109.88% (P<0.05). CONCLUSIONS: There was an apparent seasonal variation in pulmonary TB cases in Wuhan. We speculated that spring peak in our study was most likely caused by the increased reactivation of the latent TB due to vitamin D deficiency and high PM2.5 concentration, while the summer peak was mainly resulted from the enhanced winter transmission due to indoor crowding in winter, overcrowding of public transportation over the period of the Spring Festival and health care seeking delay in winter.",2014 Oct 10,"['Yang, Xiaobing', 'Duan, Qionghong', 'Wang, Jianjie', 'Zhang, Zhengbin', 'Jiang, Gaofeng']",PLoS One,,,True
0a3ef8eca5d6cd4d7a0fef83335cc02a2347492c,PMC,Rapid Isolation of Antibody from a Synthetic Human Antibody Library by Repeated Fluorescence-Activated Cell Sorting (FACS),http://dx.doi.org/10.1371/journal.pone.0108225,PMC4193741,25303314,CC BY,"Antibodies and their derivatives are the most important agents in therapeutics and diagnostics. Even after the significant progress in the technology for antibody screening from huge libraries, it takes a long time to isolate an antibody, which prevents a prompt action against the spread of a disease. Here, we report a new strategy for isolating desired antibodies from a combinatorial library in one day by repeated fluorescence-activated cell sorting (FACS). First, we constructed a library of synthetic human antibody in which single-chain variable fragment (scFv) was expressed in the periplasm of Escherichia coli. After labeling the cells with fluorescent antigen probes, the highly fluorescent cells were sorted by using a high-speed cell sorter, and these cells were reused without regeneration in the next round of sorting. After repeating this sorting, the positive clones were completely enriched in several hours. Thus, we screened the library against three viral antigens, including the H1N1 influenza virus, Hepatitis B virus, and Foot-and-mouth disease virus. Finally, the potential antibody candidates, which show K(D) values between 10 and 100 nM against the target antigens, could be successfully isolated even though the library was relatively small (∼10(6)). These results show that repeated FACS screening without regeneration of the sorted cells can be a powerful method when a rapid response to a spreading disease is required.",2014 Oct 10,"['Yim, Sung Sun', 'Bang, Hyun Bae', 'Kim, Young Hwan', 'Lee, Yong Jae', 'Jeong, Gu Min', 'Jeong, Ki Jun']",PLoS One,,,True
50f42123b5035f840369d0ff88cc55263a1394b7,PMC,The interconnected and cross-border nature of risks posed by infectious diseases,http://dx.doi.org/10.3402/gha.v7.25287,PMC4195207,25308818,CC BY,"Infectious diseases can constitute public health emergencies of international concern when a pathogen arises, acquires new characteristics, or is deliberately released, leading to the potential for loss of human lives as well as societal disruption. A wide range of risk drivers are now known to lead to and/or exacerbate the emergence and spread of infectious disease, including global trade and travel, the overuse of antibiotics, intensive agriculture, climate change, high population densities, and inadequate infrastructures, such as water treatment facilities. Where multiple risk drivers interact, the potential impact of a disease outbreak is amplified. The varying temporal and geographic frequency with which infectious disease events occur adds yet another layer of complexity to the issue. Mitigating the emergence and spread of infectious disease necessitates mapping and prioritising the interdependencies between public health and other sectors. Conversely, during an international public health emergency, significant disruption occurs not only to healthcare systems but also to a potentially wide range of sectors, including trade, tourism, energy, civil protection, transport, agriculture, and so on. At the same time, dealing with a disease outbreak may require a range of critical sectors for support. There is a need to move beyond narrow models of risk to better account for the interdependencies between health and other sectors so as to be able to better mitigate and respond to the risks posed by emerging infectious disease.",2014 Oct 10,"['Suk, Jonathan E.', 'Van Cangh, Thomas', 'Beauté, Julien', 'Bartels, Cornelius', 'Tsolova, Svetla', 'Pharris, Anastasia', 'Ciotti, Massimo', 'Semenza, Jan C.']",Glob Health Action,,,True
db361f98f584f900325b649f3ffa0e8057d0f20c,PMC,Alterations in Nerve-Evoked Bladder Contractions in a Coronavirus-Induced Mouse Model of Multiple Sclerosis,http://dx.doi.org/10.1371/journal.pone.0109314,PMC4195612,25310403,CC BY,"BACKGROUND: Patients with neurodegenerative diseases such as multiple sclerosis, Parkinson’s, and Alzheimer’s often present with lower urinary tract symptoms (LUTS, urinary frequency, urgency, nocturia and retention) resulting from damage to the peripheral and central nervous systems. These studies were designed to examine the changes in the function of the bladder that may underlie neurogenic bladder dysfunction using a mouse model of demyelination in the CNS. METHODS: Bladders from 12 week old male C57BL/6J mice with coronavirus-induced encephalomyelitis (CIE, a chronic, progressive demyelinating disease model of human MS), and age-matched controls, were cut into 5–7 strips and suspended in physiological muscle baths for tension measurement in response to agonists and electric field stimulation (EFS). Experiments were performed on intact and denuded (with mucosa removed) bladder strips. RESULTS: The maximum effect of EFS was not significantly different between CIE and control bladders. Nerve-evoked EFS contractions (tetrodotoxin-sensitive) were blocked by a combination of atropine (cholinergic antagonist) and α,β-methylene ATP (an ATP analog that desensitizes purinergic receptors). In response to EFS, the α,β-methylene ATP-resistant (cholinergic) component of contraction was significantly reduced, while the atropine-resistant (purinergic) component was significantly increased in CIE bladders. Removal of the mucosa in CIE bladders restored the cholinergic component. Bethanechol (muscarinic receptor agonist) potency was significantly increased in CIE bladders. CONCLUSIONS: Our data demonstrate a deficit in the nerve-evoked cholinergic component of contraction that is not due to the ability of the smooth muscle to respond to acetylcholine. We conclude that neurodegenerative bladder dysfunction in this model of multiple sclerosis may be due, in part, to pathologic changes in the mucosa that causes suppression of muscarinic receptor-mediated contractile response and augmentation of purinergic response of the underlying muscle. Further studies utilizing CIE mice should help elucidate the pathological changes in the mucosa resulting from demyelination in the CNS.",2014 Oct 13,"['Lamarre, Neil S.', 'Braverman, Alan S.', 'Malykhina, Anna P.', 'Barbe, Mary F.', 'Ruggieri, Michael R.']",PLoS One,,,True
ffd640ccc48cf505cf385e2a7ab7d2720e3ec427,PMC,Review: The Important Bacterial Zoonoses in “One Health” Concept,http://dx.doi.org/10.3389/fpubh.2014.00144,PMC4196475,25353010,CC BY,"An infectious disease that is transmitted from animals to humans, sometimes by a vector, is called zoonosis. The focus of this review article is on the most common emerging and re-emerging bacterial zoonotic diseases. The role of “One Health” approach, public health education, and some measures that can be taken to prevent zoonotic bacterial infections are discussed. Key points: A zoonotic bacterial disease is a disease that can be very commonly transmitted between animals and humans. Global climate changes, overuse of antimicrobials in medicine, more intensified farm settings, and closer interactions with animals facilitate emergence or re-emergence of bacterial zoonotic infections. The global “One Health” approach, which requires interdisciplinary collaborations and communications in all aspects of health care for humans, animals, and the environment, will support public health in general. New strategies for continuous dissemination of multidisciplinary research findings related to zoonotic bacterial diseases are hence needed.",2014 Oct 14,"['Cantas, Leon', 'Suer, Kaya']",Front Public Health,,,True
ae88cd3f2ac21948c74fd7b15b62cc03e9bac235,PMC,Verifying the Stability of Selected Genes for Normalization in Q PCR Experiments of Spodoptera frugiperda Cells during AcMNPV Infection,http://dx.doi.org/10.1371/journal.pone.0108516,PMC4196776,25313905,CC BY,"It is challenging to find genes with stable transcripts for use as reference genes for quantitative realtime polymerase chain reaction (qRT-PCR) during viral infection. Autographa californica nucleopolyhedrovirus (AcMNPV) is known to globally shut off host gene transcription in Sf21 cells and to modify their cytoskeletons. In this study, seven host genes were selected for validation as references for gene expression experiments using qRT-PCR. Two of them, ecdysoneless (ECD) and myosin showed stable RNA levels in our previous microarray study at 6, 12, and 24 hpi for both genes and 48 hpi for ECD. The others, actin, tubulin, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and 28S ribosome (28S), are commonly employed as reference genes for qRT-PCR. Ribosomal protein L35 (L35) gene was selected to test if ribosomal protein genes show stable RNA transcript levels similar to 28S and 18S rRNA and to validate the microarray data. In addition to 28S, previously known to have stable transcript levels, qRT-PCR showed that ECD transcript levels remained constant throughout the time course of AcMNPV infection. Transcripts of cytoskeleton genes such as actin, tubulin, and myosin declined dramatically as the infection progressed. GAPDH and L35 transcripts also declined over time. These results indicate that ECD is a reliable reference gene for qRT-PCR experiments during AcMNPV infection of Spodoptera frugiperda cells. Although 28S could be used as a reference gene for these experiments, it is less useful than ECD because of its abundance, which might make it difficult to establish an accurate baseline value for data analysis.",2014 Oct 14,"['Salem, Tamer Z.', 'Allam, Walaa R.', 'Thiem, Suzanne M.']",PLoS One,,,True
1a0304e5340ef8d016dd2f73d730072c2559acbb,PMC,Interleukin-1β Induces Blood–Brain Barrier Disruption by Downregulating Sonic Hedgehog in Astrocytes,http://dx.doi.org/10.1371/journal.pone.0110024,PMC4196962,25313834,CC BY,"The blood–brain barrier (BBB) is composed of capillary endothelial cells, pericytes, and perivascular astrocytes, which regulate central nervous system homeostasis. Sonic hedgehog (SHH) released from astrocytes plays an important role in the maintenance of BBB integrity. BBB disruption and microglial activation are common pathological features of various neurologic diseases such as multiple sclerosis, Parkinson’s disease, amyotrophic lateral sclerosis, and Alzheimer’s disease. Interleukin-1β (IL-1β), a major pro-inflammatory cytokine released from activated microglia, increases BBB permeability. Here we show that IL-1β abolishes the protective effect of astrocytes on BBB integrity by suppressing astrocytic SHH production. Astrocyte conditioned media, SHH, or SHH signal agonist strengthened BBB integrity by upregulating tight junction proteins, whereas SHH signal inhibitor abrogated these effects. Moreover, IL-1β increased astrocytic production of pro-inflammatory chemokines such as CCL2, CCL20, and CXCL2, which induce immune cell migration and exacerbate BBB disruption and neuroinflammation. Our findings suggest that astrocytic SHH is a potential therapeutic target that could be used to restore disrupted BBB in patients with neurologic diseases.",2014 Oct 14,"['Wang, Yue', 'Jin, Shijie', 'Sonobe, Yoshifumi', 'Cheng, Yi', 'Horiuchi, Hiroshi', 'Parajuli, Bijay', 'Kawanokuchi, Jun', 'Mizuno, Tetsuya', 'Takeuchi, Hideyuki', 'Suzumura, Akio']",PLoS One,,,True
8ae561e754ff3e094cd9d1e92f8517f8f9f4506a,PMC,IFITM3 Polymorphism rs12252-C Restricts Influenza A Viruses,http://dx.doi.org/10.1371/journal.pone.0110096,PMC4196997,25314048,CC BY,"The IFITM3 polymorphism rs12252-C, which encodes an IFITM3 isoform (Δ21 IFITM3) lacking 21 amino acids at the amino terminus, has been controversially associated with poor clinical outcomes in patients with H1N1 influenza A virus (IAV) infections. In vitro studies have shown that Δ21 IFITM3 loses its ability to restrict H1N1 IAV. Subsequent research has also revealed that tyrosine 20 is the key determinant for IFITM3 endocytic trafficking, which is essential for the efficient anti-viral activity of IFITM3. In contrast to previous studies, we demonstrated that both Δ21 IFITM3 and an IFITM3 variant (Y20A IFITM3), in which tyrosine 20 is substituted with alanine, strongly restricted entry mediated by IAV H1, H3, H5, and H7 proteins. Δ21 IFITM3 also efficiently suppressed replication of H1N1 and, to a lesser extent, H3N2 IAV. Δ21 IFITM3 and Y20A IFITM3 had broader subcellular distributions than full-length IFITM3 but an abundant amount of both IFITM3 variants still localized to late endosomes and lysosomes. Our data indicate that tyrosine 20 partially regulates the subcellular localization of IFITM3 but is not functionally essential for IFITM3-mediated IAV restriction. They also suggested that mechanisms, other than viral entry restriction, might contribute to variations in clinical outcomes of H1N1 influenza associated with rs12252-C.",2014 Oct 14,"['Williams, David Evan Joseph', 'Wu, Wan-Lin', 'Grotefend, Christopher Robert', 'Radic, Vladimir', 'Chung, Changik', 'Chung, Young-Hwa', 'Farzan, Michael', 'Huang, I-Chueh']",PLoS One,,,True
e2b3cf2cab4bdb3f5d357c987852c829cb4f6995,PMC,The limits of global health diplomacy: Taiwan’s observer status at the world health assembly,http://dx.doi.org/10.1186/s12992-014-0071-y,PMC4197227,25270977,CC BY,"In 2009, health authorities from Taiwan (under the name “Chinese Taipei”)(a) formally attended the 62(nd) World Health Assembly (WHA) of the World Health Organization as observers, marking the country’s participation for the first time since 1972. The long process of negotiating this breakthrough has been cited as an example of successful global health diplomacy. This paper analyses this negotiation process, drawing on government documents, formal representations from both sides of the Taiwan Strait, and key informant interviews. The actors and their motivations, along with the forums, practices and outcomes of the negotiation process, are detailed. While it is argued that non-traditional diplomatic action was important in establishing the case for Taiwan’s inclusion at the WHA, traditional concerns regarding Taiwanese sovereignty and diplomatic representation ultimately played a decisive role. The persistent influence of these traditional diplomatic questions illustrates the limits of global health diplomacy.",2014 Oct 1,"['Herington, Jonathan', 'Lee, Kelley']",Global Health,,,True
6eb145a990b1132457f78c4e1521ab827b715ad0,PMC,A Beneficiary Role for Neuraminidase in Influenza Virus Penetration through the Respiratory Mucus,http://dx.doi.org/10.1371/journal.pone.0110026,PMC4198190,25333824,CC BY,"Swine influenza virus (SIV) has a strong tropism for pig respiratory mucosa, which consists of a mucus layer, epithelium, basement membrane and lamina propria. Sialic acids present on the epithelial surface have long been considered to be determinants of influenza virus tropism. However, mucus which is also rich in sialic acids may serve as the first barrier of selection. It was investigated how influenza virus interacts with the mucus to infect epithelial cells. Two techniques were applied to track SIV H1N1 in porcine mucus. The microscopic diffusion of SIV particles in the mucus was analyzed by single particle tracking (SPT), and the macroscopic penetration of SIV through mucus was studied by a virus in-capsule-mucus penetration system, followed by visualizing the translocation of the virions with time by immunofluorescence staining. Furthermore, the effects of neuraminidase on SIV getting through or binding to the mucus were studied by using zanamivir, a neuraminidase inhibitor (NAI), and Arthrobacter ureafaciens neuraminidase. The distribution of the diffusion coefficient shows that 70% of SIV particles were entrapped, while the rest diffused freely in the mucus. Additionally, SIV penetrated the porcine mucus with time, reaching a depth of 65 µm at 30 min post virus addition, 2 fold of that at 2 min. Both the microscopic diffusion and macroscopic penetration were largely diminished by NAI, while were clearly increased by the effect of exogenous neuraminidase. Moreover, the exogenous neuraminidase sufficiently prevented the binding of SIV to mucus which was reversely enhanced by effect of NAI. These findings clearly show that the neuraminidase helps SIV move through the mucus, which is important for the virus to reach and infect epithelial cells and eventually become shed into the lumen of the respiratory tract.",2014 Oct 15,"['Yang, Xiaoyun', 'Steukers, Lennert', 'Forier, Katrien', 'Xiong, Ranhua', 'Braeckmans, Kevin', 'Van Reeth, Kristien', 'Nauwynck, Hans']",PLoS One,,,True
43c296a219a62ac9f9a632490034b6fdfc7b871e,PMC,Intestinal current measurement versus nasal potential difference measurements for diagnosis of cystic fibrosis: a case–control study,http://dx.doi.org/10.1186/1471-2466-14-156,PMC4199064,25280757,CC BY,"BACKGROUND: Nasal potential difference (NPD) and intestinal current measurement (ICM) are functional CFTR tests that are used as adjunctive diagnostic tools for cystic fibrosis (CF). Smoking has a systemic negative impact on CFTR function. A diagnostic comparison between NPD and ICM and the impact of smoking on both CFTR tests has not been done. METHODS: The sweat chloride test, NPD, and ICM were performed in 18 patients with CF (sweat chloride >60 mmol/l), including 6 pancreatic sufficient (PS) patients, and 13 healthy controls, including 8 smokers. The NPD CFTR response to Cl-free and isoproterenol perfusion (Δ0Cl(-) + Iso) was compared to the ICM CFTR response to forskolin/IBMX, carbachol, and histamine (ΔI(sc, forskolin/IBMX+ carbachol+histamine)). RESULTS: The mean NPD CFTR response and ICM CFTR response between patients with CF and healthy controls was significantly different (p <0.001), but not between patients with CF who were PS and those who were pancreatic insufficient (PI). Smokers have a decreased CFTR response measured by NPD (p = 0.049). For ICM there is a trend towards decreased CFTR response (NS). Three healthy control smokers had NPD responses within the CF-range. In contrast to NPD, there was no overlap of the ICM response between patients with CF and controls. CONCLUSIONS: ICM is superior to NPD in distinguishing between patients with CF who have a sweat chloride > 60 mmol/l and healthy controls, including smokers. Neither NPD nor ICM differentiated between patients with CF who were PS from those who were PI. Smoking has a negative impact on CFTR function in healthy controls measured by NPD and challenges the diagnostic interpretation of NPD, but not ICM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2466-14-156) contains supplementary material, which is available to authorized users.",2014 Oct 4,"['Bagheri-Hanson, Azadeh', 'Nedwed, Sebastian', 'Rueckes-Nilges, Claudia', 'Naehrlich, Lutz']",BMC Pulm Med,,,True
595f2518368eb7c7c56b8669bcf66978ac636ad1,PMC,Antibody-Validated Proteins in Inflamed Islets of Fulminant Type 1 Diabetes Profiled by Laser-Capture Microdissection Followed by Mass Spectrometry,http://dx.doi.org/10.1371/journal.pone.0107664,PMC4199548,25329145,CC BY,"BACKGROUND: There are no reports of proteomic analyses of inflamed islets in type 1 diabetes. PROCEDURES: Proteins expressed in the islets of enterovirus-associated fulminant type 1 diabetes (FT1DM) with extensive insulitis were identified by laser-capture microdissection mass spectrometry using formalin-fixed paraffin-embedded pancreatic tissues. RESULTS: Thirty-eight proteins were identified solely in FT1DM islets, most of which have not been previously linked to type 1 diabetes. Five protein-protein interacting clusters were identified, and the cellular localization of selected proteins was validated immunohistochemically. Migratory activity-related proteins, including plastin-2 (LCP1), moesin (MSN), lamin-B1 (LMNB1), Ras GTPase-activating-like protein (IQGAP1) and others, were identified in CD8(+) T cells and CD68(+) macrophages infiltrated to inflamed FT1DM islets. Proteins involved in successive signaling in innate/adaptive immunity were identified, including SAM domain and HD domain-containing protein 1 (SAMHD1), Ras GTPase-activating-like protein (IQGAP1), proteasome activator complex subunit 1 (PSME1), HLA class I histocompatibility antigen (HLA-C), and signal transducer and activator of transcription 1-alpha/beta (STAT1). Angiogenic (thymidine phosphorylase (TYMP)) and anti-angiogenic (tryptophan-tRNA ligase (WARS)) factors were identified in migrating CD8(+) T cells and CD68(+) macrophages. Proteins related to virus replication and cell proliferation, including probable ATP-dependent RNA helicase DEAD box helicase 5 (DDX5) and heterogeneous nuclear ribonucleoprotein H (HNRNPH1), were identified. The anti-apoptotic protein T-complex protein 1 subunit epsilon (CCT5), the anti-oxidative enzyme 6-phosphogluconate dehydrogenase (PDG), and the anti-viral and anti-apoptotic proteins serpin B6 (SERPINB6) and heat shock 70 kDa protein1-like (HSPA1L), were identified in FT1DM-affected islet cells. CONCLUSION: The identified FT1DM-characterizing proteins include those involved in aggressive beta cell destruction through massive immune cell migration and proteins involved in angiogenesis and islet vasculature bleeding, cell repair, and anti-inflammatory processes. Several target proteins for future type 1 diabetes interventions were identified.",2014 Oct 16,"['Nishida, Yoriko', 'Aida, Kaoru', 'Kihara, Makoto', 'Kobayashi, Tetsuro']",PLoS One,,,True
0c0e91904a6c84a7ee80cc69fe83370aaa3ca708,PMC,"Travel-related MERS-CoV cases: an assessment of exposures and risk factors in a group of Dutch travellers returning from the Kingdom of Saudi Arabia, May 2014",http://dx.doi.org/10.1186/1742-7622-11-16,PMC4200475,25328533,CC BY,"BACKGROUND: In May 2014, Middle East respiratory syndrome coronavirus (MERS-CoV) infection, with closely related viral genomes, was diagnosed in two Dutch residents, returning from a pilgrimage to Medina and Mecca, Kingdom of Saudi Arabia (KSA). These patients travelled with a group of 29 other Dutch travellers. We conducted an epidemiological assessment of the travel group to identify likely source(s) of infection and presence of potential risk factors. METHODS: All travellers, including the two cases, completed a questionnaire focussing on potential human, animal and food exposures to MERS-CoV. The questionnaire was modified from the WHO MERS-CoV questionnaire, taking into account the specific route and activities of the travel group. RESULTS: Twelve non-cases drank unpasteurized camel milk and had contact with camels. Most travellers, including one of the two patients (Case 1), visited local markets, where six of them consumed fruits. Two travellers, including Case 1, were exposed to coughing patients when visiting a hospital in Medina. Four travellers, including Case 1, visited two hospitals in Mecca. All travellers had been in contact with Case 1 while he was sick, with initially non-respiratory complaints. The cases were found to be older than the other travellers and both had co-morbidities. CONCLUSIONS: This epidemiological study revealed the complexity of MERS-CoV outbreak investigations with multiple potential exposures to MERS-CoV reported such as healthcare visits, camel exposure, and exposure to untreated food products. Exposure to MERS-CoV during a hospital visit is considered a likely source of infection for Case 1 but not for Case 2. For Case 2, the most likely source could not be determined. Exposure to MERS-CoV via direct contact with animals or dairy products seems unlikely for the two Dutch cases. Furthermore, exposure to a common but still unidentified source cannot be ruled out. More comprehensive research into sources of infection in the Arabian Peninsula is needed to strengthen and specify the prevention of MERS-CoV infections.",2014 Oct 17,"['Fanoy, Ewout B', 'van der Sande, Marianne AB', 'Kraaij-Dirkzwager, Marleen', 'Dirksen, Kees', 'Jonges, Marcel', 'van der Hoek, Wim', 'Koopmans, Marion PG', 'van der Werf, Douwe', 'Sonder, Gerard', 'van der Weijden, Charlie', 'van der Heuvel, Jet', 'Gelinck, Luc', 'Bouwhuis, Jolande W', 'van Gageldonk-Lafeber, Arianne B']",Emerg Themes Epidemiol,,,True
c4bddec0b339a9f5ea397a7390327d12c72159a2,PMC,Adaptive Management and the Value of Information: Learning Via Intervention in Epidemiology,http://dx.doi.org/10.1371/journal.pbio.1001970,PMC4204804,25333371,CC0,"Optimal intervention for disease outbreaks is often impeded by severe scientific uncertainty. Adaptive management (AM), long-used in natural resource management, is a structured decision-making approach to solving dynamic problems that accounts for the value of resolving uncertainty via real-time evaluation of alternative models. We propose an AM approach to design and evaluate intervention strategies in epidemiology, using real-time surveillance to resolve model uncertainty as management proceeds, with foot-and-mouth disease (FMD) culling and measles vaccination as case studies. We use simulations of alternative intervention strategies under competing models to quantify the effect of model uncertainty on decision making, in terms of the value of information, and quantify the benefit of adaptive versus static intervention strategies. Culling decisions during the 2001 UK FMD outbreak were contentious due to uncertainty about the spatial scale of transmission. The expected benefit of resolving this uncertainty prior to a new outbreak on a UK-like landscape would be £45–£60 million relative to the strategy that minimizes livestock losses averaged over alternate transmission models. AM during the outbreak would be expected to recover up to £20.1 million of this expected benefit. AM would also recommend a more conservative initial approach (culling of infected premises and dangerous contact farms) than would a fixed strategy (which would additionally require culling of contiguous premises). For optimal targeting of measles vaccination, based on an outbreak in Malawi in 2010, AM allows better distribution of resources across the affected region; its utility depends on uncertainty about both the at-risk population and logistical capacity. When daily vaccination rates are highly constrained, the optimal initial strategy is to conduct a small, quick campaign; a reduction in expected burden of approximately 10,000 cases could result if campaign targets can be updated on the basis of the true susceptible population. Formal incorporation of a policy to update future management actions in response to information gained in the course of an outbreak can change the optimal initial response and result in significant cost savings. AM provides a framework for using multiple models to facilitate public-health decision making and an objective basis for updating management actions in response to improved scientific understanding.",2014 Oct 21,"['Shea, Katriona', 'Tildesley, Michael J.', 'Runge, Michael C.', 'Fonnesbeck, Christopher J.', 'Ferrari, Matthew J.']",PLoS Biol,,,True
02766b20eeb39ff051a2f110def2e4bf8b9b010b,PMC,Proteome Profile of Swine Testicular Cells Infected with Porcine Transmissible Gastroenteritis Coronavirus,http://dx.doi.org/10.1371/journal.pone.0110647,PMC4204940,25333634,CC BY,"The interactions occurring between a virus and a host cell during a viral infection are complex. The purpose of this paper was to analyze altered cellular protein levels in porcine transmissible gastroenteritis coronavirus (TGEV)-infected swine testicular (ST) cells in order to determine potential virus-host interactions. A proteomic approach using isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography-tandem mass spectrometry identification was conducted on the TGEV-infected ST cells. The results showed that the 4-plex iTRAQ-based quantitative approach identified 4,112 proteins, 146 of which showed significant changes in expression 48 h after infection. At 64 h post infection, 219 of these proteins showed significant change, further indicating that a larger number of proteomic changes appear to occur during the later stages of infection. Gene ontology analysis of the altered proteins showed enrichment in multiple biological processes, including cell adhesion, response to stress, generation of precursor metabolites and energy, cell motility, protein complex assembly, growth, developmental maturation, immune system process, extracellular matrix organization, locomotion, cell-cell signaling, neurological system process, and cell junction organization. Changes in the expression levels of transforming growth factor beta 1 (TGF-β1), caspase-8, and heat shock protein 90 alpha (HSP90α) were also verified by western blot analysis. To our knowledge, this study is the first time the response profile of ST host cells following TGEV infection has been analyzed using iTRAQ technology, and our description of the late proteomic changes that are occurring after the time of vigorous viral production are novel. Therefore, this study provides a solid foundation for further investigation, and will likely help us to better understand the mechanisms of TGEV infection and pathogenesis.",2014 Oct 21,"['Ma, Ruili', 'Zhang, Yanming', 'Liu, Haiquan', 'Ning, Pengbo']",PLoS One,,,True
ba2f1457928b26ae7f4ad64983bac74a4e383378,PMC,Identification of Antigenic Proteins of the Nosocomial Pathogen Klebsiella pneumoniae,http://dx.doi.org/10.1371/journal.pone.0110703,PMC4205017,25333280,CC BY,"The continuous expansion of nosocomial infections around the globe has become a precarious situation. Key challenges include mounting dissemination of multiple resistances to antibiotics, the easy transmission and the growing mortality rates of hospital-acquired bacterial diseases. Thus, new ways to rapidly detect these infections are vital. Consequently, researchers around the globe pursue innovative approaches for point-of-care devices. In many cases the specific interaction of an antigen and a corresponding antibody is pivotal. However, the knowledge about suitable antigens is lacking. The aim of this study was to identify novel antigens as specific diagnostic markers. Additionally, these proteins might be aptly used for the generation of vaccines to improve current treatment options. Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After screening 1536 clones, 14 previously unknown immunogenic proteins were identified. Subsequently, each protein was expressed in full-length and its immunodominant character examined by ELISA and microarray analyses. Consequently, six proteins were selected for epitope mapping and three thereof possessed linear epitopes. After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. pneumoniae. The remaining epitopes showed ambiguous results regarding the specificity for K. pneumoniae. The approach adopted herein has been successfully utilized to discover novel antigens of Campylobacter jejuni and Salmonella enterica antigens before. Now, we have transferred this knowledge to the key nosocomial agent, K. pneumoniae. By identifying several novel antigens and their linear epitope sites, we have paved the way for crucial future research and applications including the design of point-of-care devices, vaccine development and serological screenings for a highly relevant nosocomial pathogen.",2014 Oct 21,"['Hoppe, Sebastian', 'Bier, Frank F.', 'von Nickisch-Rosenegk, Markus']",PLoS One,,,True
bdedfae3a14b3da115a9fd9d38823cd0a547eee6,PMC,Identification of Antigenic Proteins of the Nosocomial Pathogen Klebsiella pneumoniae,http://dx.doi.org/10.1371/journal.pone.0110703,PMC4205017,25333280,CC BY,"The continuous expansion of nosocomial infections around the globe has become a precarious situation. Key challenges include mounting dissemination of multiple resistances to antibiotics, the easy transmission and the growing mortality rates of hospital-acquired bacterial diseases. Thus, new ways to rapidly detect these infections are vital. Consequently, researchers around the globe pursue innovative approaches for point-of-care devices. In many cases the specific interaction of an antigen and a corresponding antibody is pivotal. However, the knowledge about suitable antigens is lacking. The aim of this study was to identify novel antigens as specific diagnostic markers. Additionally, these proteins might be aptly used for the generation of vaccines to improve current treatment options. Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After screening 1536 clones, 14 previously unknown immunogenic proteins were identified. Subsequently, each protein was expressed in full-length and its immunodominant character examined by ELISA and microarray analyses. Consequently, six proteins were selected for epitope mapping and three thereof possessed linear epitopes. After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. pneumoniae. The remaining epitopes showed ambiguous results regarding the specificity for K. pneumoniae. The approach adopted herein has been successfully utilized to discover novel antigens of Campylobacter jejuni and Salmonella enterica antigens before. Now, we have transferred this knowledge to the key nosocomial agent, K. pneumoniae. By identifying several novel antigens and their linear epitope sites, we have paved the way for crucial future research and applications including the design of point-of-care devices, vaccine development and serological screenings for a highly relevant nosocomial pathogen.",2014 Oct 21,"['Hoppe, Sebastian', 'Bier, Frank F.', 'von Nickisch-Rosenegk, Markus']",PLoS One,,,False
2a2a3087f3f753cbfdab460a0a31c0ac64b0cc52,PMC,Not all cows are epidemiologically equal: quantifying the risks of bovine viral diarrhoea virus (BVDV) transmission through cattle movements,http://dx.doi.org/10.1186/s13567-014-0110-y,PMC4206702,25323831,CC BY,"Many economically important cattle diseases spread between herds through livestock movements. Traditionally, most transmission models have assumed that all purchased cattle carry the same risk of generating outbreaks in the destination herd. Using data on bovine viral diarrhoea virus (BVDV) in Scotland as a case example, this study provides empirical and theoretical evidence that the risk of disease transmission varies substantially based on the animal and herd demographic characteristics at the time of purchase. Multivariable logistic regression analysis revealed that purchasing pregnant heifers and open cows sold with a calf at foot were associated with an increased risk of beef herds being seropositive for BVDV. Based on the results from a dynamic within-herd simulation model, these findings may be partly explained by the age-related probability of animals being persistently infected with BVDV as well as the herd demographic structure at the time of animal introductions. There was also evidence that an epidemiologically important network statistic, “betweenness centrality” (a measure frequently associated with the potential for herds to acquire and transmit disease), was significantly higher for herds that supplied these particular types of replacement beef cattle. The trends for dairy herds were not as clear, although there was some evidence that open heifers and open lactating cows were associated with an increased risk of BVDV. Overall, these findings have important implications for developing simulation models that more accurately reflect the industry-level transmission dynamics of infectious cattle diseases.",2014 Oct 17,"['Gates, M Carolyn', 'Humphry, Roger W', 'Gunn, George J', 'Woolhouse, Mark E J']",Vet Res,,,True
63e680dd648bb477a87f55d53d3f0ff3f2c18e0a,PMC,Transmission dynamics and control of Ebola virus disease (EVD): a review,http://dx.doi.org/10.1186/s12916-014-0196-0,PMC4207625,25300956,CC BY,"The complex and unprecedented Ebola epidemic ongoing in West Africa has highlighted the need to review the epidemiological characteristics of Ebola Virus Disease (EVD) as well as our current understanding of the transmission dynamics and the effect of control interventions against Ebola transmission. Here we review key epidemiological data from past Ebola outbreaks and carry out a comparative review of mathematical models of the spread and control of Ebola in the context of past outbreaks and the ongoing epidemic in West Africa. We show that mathematical modeling offers useful insights into the risk of a major epidemic of EVD and the assessment of the impact of basic public health measures on disease spread. We also discuss the critical need to collect detailed epidemiological data in real-time during the course of an ongoing epidemic, carry out further studies to estimate the effectiveness of interventions during past outbreaks and the ongoing epidemic, and develop large-scale modeling studies to study the spread and control of viral hemorrhagic fevers in the context of the highly heterogeneous economic reality of African countries.",2014 Oct 10,"['Chowell, Gerardo', 'Nishiura, Hiroshi']",BMC Med,,,True
2b7d5e5ebeba8a9731ed1e98a3ee177499fed7db,PMC,Hepatitis C Virus Infection as a Traumatic Experience,http://dx.doi.org/10.1371/journal.pone.0110529,PMC4207714,25340574,CC BY,"OBJECTIVE: The purpose of this study was to evaluate whether individuals consider their HCV infection to be a potentially traumatic experience. Additionally, we investigated its association with Post-Traumatic Stress Disorder (PTSD) and the impact of PTSD diagnosis on health-related quality of life (HRQoL) in HCV infected subjects. METHODS: We conducted a cross-sectional survey of 127 HCV-infected outpatients recruited at a University Hospital in Salvador, Brazil. All subjects answered an orally-administered questionnaire to gather clinical and socio-demographic data. We investigated traumatic experiences and the subject's perception of the disease using the Trauma History Questionnaire. PTSD and other psychiatric diagnoses were assessed through the Mini International Neuropsychiatric Interview-Brazilian Version 5.0.0 (M.I.N.I. PLUS). HRQoL was assessed using Short-Form 36 (SF-36). RESULTS: Approximately 38.6% of the patients considered hepatitis C to be a traumatic experience. Of these, 60.7% had a PTSD diagnosis. PTSD was associated with significant impairment in quality of life for individuals in seven SF-36 domains as shown bymultivariate analysis: Role-Physical (β: −24.85; 95% CI: −42.08; −7.61), Bodily Pain (β: −19.36; 95% CI: −31.28; −7.45), General Health (β: −20.79; 95% CI: −29.65; −11.92), Vitality (β: −11.92; 95% CI: −20.74; −3.1), Social Functioning (β: −34.73; 95% CI: −46.79; −22.68), Role-Emotional (β: −26.07; 95% CI: −44.61; −7.53), Mental Health (β: −17.46; 95% CI: −24.38; −10.54). CONCLUSION: HCV is frequently a traumatic experience and it is strongly associated with PTSD diagnosis. PTSD significantly impaired HRQoL.",2014 Oct 23,"['Morais-de-Jesus, Mychelle', 'Daltro-Oliveira, Renato', 'Pettersen, Karine Miranda', 'Dantas-Duarte, Adriana', 'Amaral, Luciana Di-Domizio', 'Cavalcanti-Ribeiro, Patrícia', 'Santos, Carlos Teles', 'Schinoni, Maria Isabel', 'Netto, Liana R.', 'Araújo-de-Freitas, Lucas', 'Paraná, Raymundo', 'Miranda-Scippa, Ângela', 'Koenen, Karestan C.', 'Quarantini, Lucas C.']",PLoS One,,,True
bb6be6d67dbc92ee528f4c09ca1643eeda4316bd,PMC,Epidemiological and Virological Characteristics of Influenza Viruses Circulating in Cambodia from 2009 to 2011,http://dx.doi.org/10.1371/journal.pone.0110713,PMC4207757,25340711,CC0,"BACKGROUND: The Cambodian National Influenza Center (NIC) monitored and characterized circulating influenza strains from 2009 to 2011. METHODOLOGY/PRINCIPAL FINDINGS: Sentinel and study sites collected nasopharyngeal specimens for diagnostic detection, virus isolation, antigenic characterization, sequencing and antiviral susceptibility analysis from patients who fulfilled case definitions for influenza-like illness, acute lower respiratory infections and event-based surveillance. Each year in Cambodia, influenza viruses were detected mainly from June to November, during the rainy season. Antigenic analysis show that A/H1N1pdm09 isolates belonged to the A/California/7/2009-like group. Circulating A/H3N2 strains were A/Brisbane/10/2007-like in 2009 before drifting to A/Perth/16/2009-like in 2010 and 2011. The Cambodian influenza B isolates from 2009 to 2011 all belonged to the B/Victoria lineage represented by the vaccine strains B/Brisbane/60/2008 and B/Malaysia/2506/2004. Sequences of the M2 gene obtained from representative 2009–2011 A/H3N2 and A/H1N1pdm09 strains all contained the S31N mutation associated with adamantanes resistance except for one A/H1N1pdm09 strain isolated in 2011 that lacked this mutation. No reduction in the susceptibility to neuraminidase inhibitors was observed among the influenza viruses circulating from 2009 to 2011. Phylogenetic analysis revealed that A/H3N2 strains clustered each year to a distinct group while most A/H1N1pdm09 isolates belonged to the S203T clade. CONCLUSIONS/SIGNIFICANCE: In Cambodia, from 2009 to 2011, influenza activity occurred throughout the year with peak seasonality during the rainy season from June to November. Seasonal influenza epidemics were due to multiple genetically distinct viruses, even though all of the isolates were antigenically similar to the reference vaccine strains. The drug susceptibility profile of Cambodian influenza strains revealed that neuraminidase inhibitors would be the drug of choice for influenza treatment and chemoprophylaxis in Cambodia, as adamantanes are no longer expected to be effective.",2014 Oct 23,"['Horm, Srey Viseth', 'Mardy, Sek', 'Rith, Sareth', 'Ly, Sovann', 'Heng, Seng', 'Vong, Sirenda', 'Kitsutani, Paul', 'Ieng, Vannra', 'Tarantola, Arnaud', 'Ly, Sowath', 'Sar, Borann', 'Chea, Nora', 'Sokhal, Buth', 'Barr, Ian', 'Kelso, Anne', 'Horwood, Paul F.', 'Timmermans, Ans', 'Hurt, Aeron', 'Lon, Chanthap', 'Saunders, David', 'Ung, Sam An', 'Asgari, Nima', 'Roces, Maria Concepcion', 'Touch, Sok', 'Komadina, Naomi', 'Buchy, Philippe']",PLoS One,,,True
e50473adb66bac4a176d80051d63f415d2dbd5a8,PMC,Integrin β3 Is Required in Infection and Proliferation of Classical Swine Fever Virus,http://dx.doi.org/10.1371/journal.pone.0110911,PMC4207786,25340775,CC BY,"Classical Swine Fever (CSF) is a highly infectious fatal pig disease, resulting in huge economic loss to the swine industry. Integrins are membrane-bound signal mediators, expressed on a variety of cell surfaces and are known as receptors or co-receptors for many viruses. However, the role of integrin β3 in CSFV infection is unknown. Here, through quantitive PCR, immunofluorescence (IFC) and immunocytohistochemistry (ICC), we revealed that ST (swine testicles epithelial) cells have a prominent advantage in CSFV proliferation as compared to EC (swine umbilical vein endothelial cell), IEC (swine intestinal epithelial cell) and PK (porcine kidney epithelial) cells. Meanwhile, ST cells had remarkably more integrin β3 expression as compared to EC, IEC and PK cells, which was positively correlated with CSFV infection and proliferation. Integrin β3 was up-regulated post CSFV infection in all the four cell lines, while the CSFV proliferation rate was decreased in integrin β3 function-blocked cells. ShRNA1755 dramatically decreased integrin β3, with a deficiency of 96% at the mRNA level and 80% at the protein level. CSFV proliferation was dramatically reduced in integrin β3 constantly-defected cells (ICDC), with the deficiencies of 92.6%, 99% and 81.7% at 24 h, 48 h and 72 h post CSFV infection, respectively. These results demonstrate that integrin β3 is required in CSFV infection and proliferation, which provide a new insight into the mechanism of CSFV infection.",2014 Oct 23,"['Li, Weiwei', 'Wang, Gang', 'Liang, Wulong', 'Kang, Kai', 'Guo, Kangkang', 'Zhang, Yanming']",PLoS One,,,True
63cbd57061c1709dc5aca57716a3ab95f6ba6446,PMC,Growth Patterns and Scaling Laws Governing AIDS Epidemic in Brazilian Cities,http://dx.doi.org/10.1371/journal.pone.0111015,PMC4207789,25340796,CC BY,"Brazil holds approximately 1/3 of population living infected with AIDS (acquired immunodeficiency syndrome) in Central and South Americas, and it was also the first developing country to implement a large-scale control and intervention program against AIDS epidemic. In this scenario, we investigate the temporal evolution and current status of the AIDS epidemic in Brazil. Specifically, we analyze records of annual absolute frequency of cases for more than 5000 cities for the first 33 years of the infection in Brazil. We found that (i) the annual absolute frequencies exhibit a logistic-type growth with an exponential regime in the first few years of the AIDS spreading; (ii) the actual reproduction number decaying as a power law; (iii) the distribution of the annual absolute frequencies among cities decays with a power law behavior; (iv) the annual absolute frequencies and the number of inhabitants have an allometric relationship; (v) the temporal evolution of the annual absolute frequencies have different profile depending on the average annual absolute frequencies in the cities. These findings yield a general quantitative description of the AIDS infection dynamics in Brazil since the beginning. They also provide clues about the effectiveness of treatment and control programs against the infection, that has had a different impact depending on the number of inhabitants of cities. In this framework, our results give insights into the overall dynamics of AIDS epidemic, which may contribute to select empirically accurate models.",2014 Oct 23,"['Antonio, Fernando Jose', 'de Picoli, Sergio', 'Teixeira, Jorge Juarez Vieira', 'Mendes, Renio dos Santos']",PLoS One,,,True
64053a0785373722d802b6a2fac9db7489b1474e,PMC,"Contact Heterogeneity, Rather Than Transmission Efficiency, Limits the Emergence and Spread of Canine Influenza Virus",http://dx.doi.org/10.1371/journal.ppat.1004455,PMC4207809,25340642,CC BY,"Host-range shifts in influenza virus are a major risk factor for pandemics. A key question in the study of emerging zoonoses is how the evolution of transmission efficiency interacts with heterogeneity in contact patterns in the new host species, as this interplay influences disease dynamics and prospects for control. Here we use a synergistic mixture of models and data to tease apart the evolutionary and demographic processes controlling a host-range shift in equine H3N8-derived canine influenza virus (CIV). CIV has experienced 15 years of continuous transfer among dogs in the United States, but maintains a patchy distribution, characterized by sporadic short-lived outbreaks coupled with endemic hotspots in large animal shelters. We show that CIV has a high reproductive potential in these facilities (mean R(0) = 3.9) and that these hotspots act as refugia from the sparsely connected majority of the dog population. Intriguingly, CIV has evolved a transmission efficiency that closely matches the minimum required to persist in these refugia, leaving it poised on the extinction/invasion threshold of the host contact network. Corresponding phylogenetic analyses show strong geographic clustering in three US regions, and that the effective reproductive number of the virus (R(e)) in the general dog population is close to 1.0. Our results highlight the critical role of host contact structure in CIV dynamics, and show how host contact networks could shape the evolution of pathogen transmission efficiency. Importantly, efficient control measures could eradicate the virus, in turn minimizing the risk of future sustained transmission among companion dogs that could represent a potential new axis to the human-animal interface for influenza.",2014 Oct 23,"['Dalziel, Benjamin D.', 'Huang, Kai', 'Geoghegan, Jemma L.', 'Arinaminpathy, Nimalan', 'Dubovi, Edward J.', 'Grenfell, Bryan T.', 'Ellner, Stephen P.', 'Holmes, Edward C.', 'Parrish, Colin R.']",PLoS Pathog,,,True
4c6112b657933e7254342266bc7afdeb42af507d,PMC,"Contact Heterogeneity, Rather Than Transmission Efficiency, Limits the Emergence and Spread of Canine Influenza Virus",http://dx.doi.org/10.1371/journal.ppat.1004455,PMC4207809,25340642,CC BY,"Host-range shifts in influenza virus are a major risk factor for pandemics. A key question in the study of emerging zoonoses is how the evolution of transmission efficiency interacts with heterogeneity in contact patterns in the new host species, as this interplay influences disease dynamics and prospects for control. Here we use a synergistic mixture of models and data to tease apart the evolutionary and demographic processes controlling a host-range shift in equine H3N8-derived canine influenza virus (CIV). CIV has experienced 15 years of continuous transfer among dogs in the United States, but maintains a patchy distribution, characterized by sporadic short-lived outbreaks coupled with endemic hotspots in large animal shelters. We show that CIV has a high reproductive potential in these facilities (mean R(0) = 3.9) and that these hotspots act as refugia from the sparsely connected majority of the dog population. Intriguingly, CIV has evolved a transmission efficiency that closely matches the minimum required to persist in these refugia, leaving it poised on the extinction/invasion threshold of the host contact network. Corresponding phylogenetic analyses show strong geographic clustering in three US regions, and that the effective reproductive number of the virus (R(e)) in the general dog population is close to 1.0. Our results highlight the critical role of host contact structure in CIV dynamics, and show how host contact networks could shape the evolution of pathogen transmission efficiency. Importantly, efficient control measures could eradicate the virus, in turn minimizing the risk of future sustained transmission among companion dogs that could represent a potential new axis to the human-animal interface for influenza.",2014 Oct 23,"['Dalziel, Benjamin D.', 'Huang, Kai', 'Geoghegan, Jemma L.', 'Arinaminpathy, Nimalan', 'Dubovi, Edward J.', 'Grenfell, Bryan T.', 'Ellner, Stephen P.', 'Holmes, Edward C.', 'Parrish, Colin R.']",PLoS Pathog,,,False
36c1c6bc314487fe898f76a7093175d90347ac20,PMC,Genetic polymorphisms and risk of recurrent wheezing in pediatric age,http://dx.doi.org/10.1186/1471-2466-14-162,PMC4210469,25326706,CC BY,"BACKGROUND: Wheezing during early life is a very common disorder, but the reasons underlying the different wheezing phenotypes are still unclear. The aims of this study were to analyse the potential correlations between the risk of developing recurrent wheezing and the presence of specific polymorphisms of some genes regulating immune system function, and to study the relative importance of the associations of different viruses and genetic polymorphisms in causing recurrent episodes. METHODS: The study involved 119 otherwise healthy infants admitted to hospital for a first episode of wheezing (74 of whom subsequently experienced recurrent episodes) and 119 age- and sex-matched subjects without any history of respiratory problem randomly selected from those attending our outpatient clinic during the study period. All of the study subjects were followed up for two years, and 47 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped on whole blood using an ABI PRISM 7900 HT Fast Real-time instrument. RESULTS: IL8-rs4073AT, VEGFA-rs833058CT, MBL2-rs1800450CT and IKBKB-rs3747811AT were associated with a significantly increased risk of developing wheezing (p = 0.02, p = 0.03, p = 0.05 and p = 0.0018), whereas CTLA4-rs3087243AG and NFKBIB-rs3136641TT were associated with a significantly reduced risk (p = 0.05 and p = 0.04). IL8-rs4073AT, VEGFA-rs2146323AA and NFKBIA-rs2233419AG were associated with a significantly increased risk of developing recurrent wheezing (p = 0.04, p = 0.04 and p = 0.03), whereas TLR3-rs3775291TC was associated with a significantly reduced risk (p = 0.03). Interestingly, the study of gene-environment interactions showed that rhinovirus was significantly associated with recurrent wheezing in the presence of IL4Ra-rs1801275GG and G (odds ratio [OR] 6.03, 95% confidence interval [CI]: 1.21-30.10, p = 0.03) and MAP3K1-rs702689AA (OR 4.09, 95% CI: 1.14-14.61, p = 0.03). CONCLUSIONS: This study shows a clear relationship between the risk of wheezing and polymorphisms of some genes involved in the immune response. Although further studies are needed to confirm the results, these findings may be useful for the early identification of children at the highest risk of developing recurrent episodes and possibly subsequent asthma.",2014 Oct 18,"['Esposito, Susanna', 'Ierardi, Valentina', 'Daleno, Cristina', 'Scala, Alessia', 'Terranova, Leonardo', 'Tagliabue, Claudia', 'Rios, Walter Peves', 'Pelucchi, Claudio', 'Principi, Nicola']",BMC Pulm Med,,,True
5bae3e47050469780ae94d2f254ab80221178ebf,PMC,Autoimmune and Neoplastic Thyroid Diseases Associated with Hepatitis C Chronic Infection,http://dx.doi.org/10.1155/2014/935131,PMC4211174,25374602,CC BY,"Frequently, patients with hepatitis C virus (HCV) chronic infection have high levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies, ultrasonographic signs of chronic autoimmune thyroiditis, and subclinical hypothyroidism, in female gender versus healthy controls, or hepatitis B virus infected patients. In patients with “HCV-associated mixed cryoglobulinemia” (MC + HCV), a higher prevalence of thyroid autoimmune disorders was shown not only compared to controls, but also versus HCV patients without cryoglobulinemia. Patients with MC + HCV or HCV chronic infection show a higher prevalence of papillary thyroid cancer than controls, in particular in patients with autoimmune thyroiditis. Patients with HCV chronic infection, or with MC + HCV, in presence of autoimmune thyroiditis, show higher serum levels of T-helper (Th)1 (C-X-C motif) ligand 10 (CXCL10) chemokine, but normal levels of Th2 (C-C motif) ligand 2 chemokine, than patients without thyroiditis. HCV thyroid infection could act by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1 lymphocytes that secrete interferon-γ and tumor necrosis factor-α. These cytokines might induce a further CXCL10 secretion by thyrocytes, thus perpetuating the immune cascade, which may lead to the appearance of autoimmune thyroid disorders in genetically predisposed subjects. A careful monitoring of thyroid function, particularly where nodules occur, is recommended in HCV patients.",2014 Oct 13,"['Fallahi, Poupak', 'Ferrari, Silvia Martina', 'Politti, Ugo', 'Giuggioli, Dilia', 'Ferri, Clodoveo', 'Antonelli, Alessandro']",Int J Endocrinol,,,True
60a7721ab454f05f6622087ecde3b186b505779f,PMC,Isolation Facilities for Highly Infectious Diseases in Europe – A Cross-Sectional Analysis in 16 Countries,http://dx.doi.org/10.1371/journal.pone.0100401,PMC4211666,25350843,CC BY,"BACKGROUND: Highly Infectious Diseases (HIDs) are (i) easily transmissible form person to person; (ii) cause a life-threatening illness with no or few treatment options; and (iii) pose a threat for both personnel and the public. Hence, even suspected HID cases should be managed in specialised facilities minimizing infection risks but allowing state-of-the-art critical care. Consensus statements on the operational management of isolation facilities have been published recently. The study presented was set up to compare the operational management, resources, and technical equipment among European isolation facilities. Due to differences in geography, population density, and national response plans it was hypothesized that adherence to recommendations will vary. METHODS AND FINDINGS: Until mid of 2010 the European Network for Highly Infectious Diseases conducted a cross-sectional analysis of isolation facilities in Europe, recruiting 48 isolation facilities in 16 countries. Three checklists were disseminated, assessing 44 items and 148 specific questions. The median feedback rate for specific questions was 97.9% (n = 47/48) (range: n = 7/48 (14.6%) to n = 48/48 (100%). Although all facilities enrolled were nominated specialised facilities' serving countries or regions, their design, equipment and personnel management varied. Eighteen facilities fulfilled the definition of a High Level Isolation Unit'. In contrast, 24 facilities could not operate independently from their co-located hospital, and five could not ensure access to equipment essential for infection control. Data presented are not representative for the EU in general, as only 16/27 (59.3%) of all Member States agreed to participate. Another limitation of this study is the time elapsed between data collection and publication; e.g. in Germany one additional facility opened in the meantime. CONCLUSION: There are disparities both within and between European countries regarding the design and equipment of isolation facilities. With regard to the International Health Regulations, terminology, capacities and equipment should be standardised.",2014 Oct 28,"['Schilling, Stefan', 'Fusco, Francesco Maria', 'De Iaco, Giuseppina', 'Bannister, Barbara', 'Maltezou, Helena C.', 'Carson, Gail', 'Gottschalk, Rene', 'Brodt, Hans-Reinhard', 'Brouqui, Philippe', 'Puro, Vincenzo', 'Ippolito, Giuseppe', None]",PLoS One,,,True
9b2ee0cdb3b92a377acec0e84a63090005b6b7ed,PMC,Identification of Protein Interaction Partners in Mammalian Cells Using SILAC-immunoprecipitation Quantitative Proteomics,http://dx.doi.org/10.3791/51656,PMC4212580,25046639,CC BY,"Quantitative proteomics combined with immuno-affinity purification, SILAC immunoprecipitation, represent a powerful means for the discovery of novel protein:protein interactions. By allowing the accurate relative quantification of protein abundance in both control and test samples, true interactions may be easily distinguished from experimental contaminants. Low affinity interactions can be preserved through the use of less-stringent buffer conditions and remain readily identifiable. This protocol discusses the labeling of tissue culture cells with stable isotope labeled amino acids, transfection and immunoprecipitation of an affinity tagged protein of interest, followed by the preparation for submission to a mass spectrometry facility. This protocol then discusses how to analyze and interpret the data returned from the mass spectrometer in order to identify cellular partners interacting with a protein of interest. As an example this technique is applied to identify proteins binding to the eukaryotic translation initiation factors: eIF4AI and eIF4AII.",2014 Jul 6,"['Emmott, Edward', 'Goodfellow, Ian']",J Vis Exp,,,True
a3156b64bff879eba0b2b9a0e81adc1c5dead42c,PMC,Harnessing Mechanistic Knowledge on Beneficial Versus Deleterious IFN-I Effects to Design Innovative Immunotherapies Targeting Cytokine Activity to Specific Cell Types,http://dx.doi.org/10.3389/fimmu.2014.00526,PMC4214202,25400632,CC BY,"Type I interferons (IFN-I) were identified over 50 years ago as cytokines critical for host defense against viral infections. IFN-I promote anti-viral defense through two main mechanisms. First, IFN-I directly reinforce or induce de novo in potentially all cells the expression of effector molecules of intrinsic anti-viral immunity. Second, IFN-I orchestrate innate and adaptive anti-viral immunity. However, IFN-I responses can be deleterious for the host in a number of circumstances, including secondary bacterial or fungal infections, several autoimmune diseases, and, paradoxically, certain chronic viral infections. We will review the proposed nature of protective versus deleterious IFN-I responses in selected diseases. Emphasis will be put on the potentially deleterious functions of IFN-I in human immunodeficiency virus type 1 (HIV-1) infection, and on the respective roles of IFN-I and IFN-III in promoting resolution of hepatitis C virus (HCV) infection. We will then discuss how the balance between beneficial versus deleterious IFN-I responses is modulated by several key parameters including (i) the subtypes and dose of IFN-I produced, (ii) the cell types affected by IFN-I, and (iii) the source and timing of IFN-I production. Finally, we will speculate how integration of this knowledge combined with advanced biochemical manipulation of the activity of the cytokines should allow designing innovative immunotherapeutic treatments in patients. Specifically, we will discuss how induction or blockade of specific IFN-I responses in targeted cell types could promote the beneficial functions of IFN-I and/or dampen their deleterious effects, in a manner adapted to each disease.",2014 Oct 30,"['Tomasello, Elena', 'Pollet, Emeline', 'Vu Manh, Thien-Phong', 'Uzé, Gilles', 'Dalod, Marc']",Front Immunol,,,True
28f13f534ff3d7fccd966a9bb1158a0a1ed95967,PMC,Spatial Analysis on Hepatitis C Virus Infection in Mainland China: From 2005 to 2011,http://dx.doi.org/10.1371/journal.pone.0110861,PMC4214689,25356554,CC BY,"BACKGROUND: The burden of Hepatitis C virus (HCV) has become more and more considerable in China. A macroscopic spatial analysis of HCV infection that can provide scientific information for further intervention and disease control is lacking. METHODS: All geo-referenced HCV cases that had been recorded by the China Information System for Disease Control and Prevention (CISDCP) during 2005–2011 were included in the study. In order to learn about the changes of demographic characteristics and geographic distribution, trend test and spatial analysis were conducted to reflect the changing pattern of HCV infection. RESULTS: Over 770,000 identified HCV infection cases had specific geographic information during the study period (2005–2011). Ratios of gender (Male/Female, Z-value = −18.53, P<0.001), age group (≤30 years old/≥31 years old, Z-value = −51.03, P<0.001) and diagnosis type (Clinical diagnosis/Laboratory diagnosis, Z-value = −130.47, P<0.001) declined. HCV infection was not distributed randomly. Provinces Henan, Guangdong, Guangxi, Xinjiang, and Jilin reported more than 40,000 HCV infections during 2005 to 2011, accounting for 43.91% of all cases. The strength of cluster of disease was increasing in China during the study period. Overall, 11 provinces had once been detected as hotspots during 7 years, most of which were located in the central or border parts of China. Tibet, Qinghai, Jiangxi were the regions that had coldspots. CONCLUSIONS: The number of clustering of HCV infection among older adults increased in recent years. Specific interventions and prevention programs targeting at main HCV epidemic areas are urgently in need in mainland China.",2014 Oct 30,"['Wang, Lu', 'Xing, Jiannan', 'Chen, Fangfang', 'Yan, Ruixue', 'Ge, Lin', 'Qin, Qianqian', 'Wang, Liyan', 'Ding, Zhengwei', 'Guo, Wei', 'Wang, Ning']",PLoS One,,,True
a034fc1a3e926d0e12339678c32e892c37f514cb,PMC,Detecting Differential Transmissibilities That Affect the Size of Self-Limited Outbreaks,http://dx.doi.org/10.1371/journal.ppat.1004452,PMC4214794,25356657,CC0,"Our ability to respond appropriately to infectious diseases is enhanced by identifying differences in the potential for transmitting infection between individuals. Here, we identify epidemiological traits of self-limited infections (i.e. infections with an effective reproduction number satisfying [Image: see text]) that correlate with transmissibility. Our analysis is based on a branching process model that permits statistical comparison of both the strength and heterogeneity of transmission for two distinct types of cases. Our approach provides insight into a variety of scenarios, including the transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the Arabian peninsula, measles in North America, pre-eradication smallpox in Europe, and human monkeypox in the Democratic Republic of the Congo. When applied to chain size data for MERS-CoV transmission before 2014, our method indicates that despite an apparent trend towards improved control, there is not enough statistical evidence to indicate that [Image: see text] has declined with time. Meanwhile, chain size data for measles in the United States and Canada reveal statistically significant geographic variation in [Image: see text], suggesting that the timing and coverage of national vaccination programs, as well as contact tracing procedures, may shape the size distribution of observed infection clusters. Infection source data for smallpox suggests that primary cases transmitted more than secondary cases, and provides a quantitative assessment of the effectiveness of control interventions. Human monkeypox, on the other hand, does not show evidence of differential transmission between animals in contact with humans, primary cases, or secondary cases, which assuages the concern that social mixing can amplify transmission by secondary cases. Lastly, we evaluate surveillance requirements for detecting a change in the human-to-human transmission of monkeypox since the cessation of cross-protective smallpox vaccination. Our studies lay the foundation for future investigations regarding how infection source, vaccination status or other putative transmissibility traits may affect self-limited transmission.",2014 Oct 30,"['Blumberg, Seth', 'Funk, Sebastian', 'Pulliam, Juliet R. C.']",PLoS Pathog,,,True
917fc85b2bd24410181d77246ad89c49e5d6f7b0,PMC,Detecting Differential Transmissibilities That Affect the Size of Self-Limited Outbreaks,http://dx.doi.org/10.1371/journal.ppat.1004452,PMC4214794,25356657,CC0,"Our ability to respond appropriately to infectious diseases is enhanced by identifying differences in the potential for transmitting infection between individuals. Here, we identify epidemiological traits of self-limited infections (i.e. infections with an effective reproduction number satisfying [Image: see text]) that correlate with transmissibility. Our analysis is based on a branching process model that permits statistical comparison of both the strength and heterogeneity of transmission for two distinct types of cases. Our approach provides insight into a variety of scenarios, including the transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the Arabian peninsula, measles in North America, pre-eradication smallpox in Europe, and human monkeypox in the Democratic Republic of the Congo. When applied to chain size data for MERS-CoV transmission before 2014, our method indicates that despite an apparent trend towards improved control, there is not enough statistical evidence to indicate that [Image: see text] has declined with time. Meanwhile, chain size data for measles in the United States and Canada reveal statistically significant geographic variation in [Image: see text], suggesting that the timing and coverage of national vaccination programs, as well as contact tracing procedures, may shape the size distribution of observed infection clusters. Infection source data for smallpox suggests that primary cases transmitted more than secondary cases, and provides a quantitative assessment of the effectiveness of control interventions. Human monkeypox, on the other hand, does not show evidence of differential transmission between animals in contact with humans, primary cases, or secondary cases, which assuages the concern that social mixing can amplify transmission by secondary cases. Lastly, we evaluate surveillance requirements for detecting a change in the human-to-human transmission of monkeypox since the cessation of cross-protective smallpox vaccination. Our studies lay the foundation for future investigations regarding how infection source, vaccination status or other putative transmissibility traits may affect self-limited transmission.",2014 Oct 30,"['Blumberg, Seth', 'Funk, Sebastian', 'Pulliam, Juliet R. C.']",PLoS Pathog,,,True
7e79ee45307f38f4d8935a6ac728ee4d089a0d53,PMC,Detecting Differential Transmissibilities That Affect the Size of Self-Limited Outbreaks,http://dx.doi.org/10.1371/journal.ppat.1004452,PMC4214794,25356657,CC0,"Our ability to respond appropriately to infectious diseases is enhanced by identifying differences in the potential for transmitting infection between individuals. Here, we identify epidemiological traits of self-limited infections (i.e. infections with an effective reproduction number satisfying [Image: see text]) that correlate with transmissibility. Our analysis is based on a branching process model that permits statistical comparison of both the strength and heterogeneity of transmission for two distinct types of cases. Our approach provides insight into a variety of scenarios, including the transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the Arabian peninsula, measles in North America, pre-eradication smallpox in Europe, and human monkeypox in the Democratic Republic of the Congo. When applied to chain size data for MERS-CoV transmission before 2014, our method indicates that despite an apparent trend towards improved control, there is not enough statistical evidence to indicate that [Image: see text] has declined with time. Meanwhile, chain size data for measles in the United States and Canada reveal statistically significant geographic variation in [Image: see text], suggesting that the timing and coverage of national vaccination programs, as well as contact tracing procedures, may shape the size distribution of observed infection clusters. Infection source data for smallpox suggests that primary cases transmitted more than secondary cases, and provides a quantitative assessment of the effectiveness of control interventions. Human monkeypox, on the other hand, does not show evidence of differential transmission between animals in contact with humans, primary cases, or secondary cases, which assuages the concern that social mixing can amplify transmission by secondary cases. Lastly, we evaluate surveillance requirements for detecting a change in the human-to-human transmission of monkeypox since the cessation of cross-protective smallpox vaccination. Our studies lay the foundation for future investigations regarding how infection source, vaccination status or other putative transmissibility traits may affect self-limited transmission.",2014 Oct 30,"['Blumberg, Seth', 'Funk, Sebastian', 'Pulliam, Juliet R. C.']",PLoS Pathog,,,False
ba7a60024505cd93efc22344fc0c956bad66d6e8,PMC,Mouse Hepatitis Virus Infection Upregulates Genes Involved in Innate Immune Responses,http://dx.doi.org/10.1371/journal.pone.0111351,PMC4216085,25360880,CC BY,"Neurotropic recombinant strain of Mouse Hepatitis Virus, RSA59, induces meningo-encephalitis, myelitis and demyelination following intracranial inoculation. RSA59 induced neuropathology is partially caused by activation of CNS resident microglia, as demonstrated by changes in cellular morphology and increased expression of a microglia/macrophage specific calcium ion binding factor, Iba1. Affymetrix Microarray analysis for mRNA expression data reveals expression of inflammatory mediators that are known to be released by activated microglia. Microglia-specific cell surface molecules, including CD11b, CD74, CD52 and CD68, are significantly upregulated in contrast to CD4, CD8 and CD19. Protein analysis of spinal cord extracts taken from mice 6 days post-inoculation, the time of peak inflammation, reveals robust expression of IFN-γ, IL-12 and mKC. Data suggest that activated microglia and inflammatory mediators contribute to a local CNS microenvironment that regulates viral replication and IFN-γ production during the acute phase of infection, which in turn can cause phagolysosome maturation and phagocytosis of the myelin sheath, leading to demyelination.",2014 Oct 31,"['Chatterjee, Dhriti', 'Addya, Sankar', 'Khan, Reas S.', 'Kenyon, Lawrence C.', 'Choe, Alexander', 'Cohrs, Randall J.', 'Shindler, Kenneth S.', 'Sarma, Jayasri Das']",PLoS One,,,True
f84decc775e81850bbfcbf71972377db10e4863c,PMC,Semen banking: consideration on viral contamination in the era of new emerging viral infection,,PMC4216451,25587263,CC BY,,2011 Spring,"Wiwanitkit, Viroj",Iran J Reprod Med,,,True
7ac11579d3d1602c4ebceee735a88cb465ff057b,PMC,The Effect of Aqueous Extract of Glycyrrhiza glabra on Herpes Simplex Virus 1,http://dx.doi.org/10.5812/jjm.11616,PMC4216581,25368801,CC BY,"BACKGROUND: Herpes Simplex Virus 1 (HSV-1) resistance to drugs and the side effects of drugs have drawn the attention of investigators to herbal plants. OBJECTIVES: The main aim of the current research was to investigate the effects of Glycyrrhiza glabra (liquorice root) on HSV-1. One of the objectives of the current research was to determine the efficacy and the effect of the elapsed incubation time of treating the Vero cells infected with HSV-1 by G. glabra. In addition, the effect of cells pretreatment with licorice root extract, preincubation of virus with licorice root extract, and the antiviral activity were assessed. PATIENTS AND METHODS: Vero cells were incubated after adding different concentrations of aqueous extracts of G. glabra. The cells were incubated during various time courses. Cytotoxicity assay, determining the 50% tissue culture infectious dose (TCID(50)), and incubation of HSV-1 with licorice root extract prior to viral infection were performed. RESULTS: Internal association among different experiment groups showed the significant difference in the efficacy of the extract with regard to incubation period between one and four hours, one and eight hours, four and 12 hours, and eight and 12 hours. Moreover, there was a significant difference with regard to efficacy among the pretreatment of cells with extract for two hours, incubation of virus with extract for one hour, incubation of virus with extract for two hours. CONCLUSIONS: G. glabra showed the characteristics of a novel antiviral medication; however, more in vitro experiments are needed to determine the antiherpetic activities of the G. glabra.",2014 Jul 1,"['Sabouri Ghannad, Masoud', 'Mohammadi, Avid', 'Safiallahy, Sohayla', 'Faradmal, Javad', 'Azizi, Mona', 'Ahmadvand, Zohreh']",Jundishapur J Microbiol,,,True
0926342a9cad40463ea13641523a95b165da8f8b,PMC,The quest for effective Ebola treatment: Ebola VP35 is an evidence-based target for dsRNA drugs,http://dx.doi.org/10.1038/emi.2014.77,PMC4217096,26038500,CC BY,,2014 Oct 29,"['Mitchell, William M', 'Carter, William A']",Emerg Microbes Infect,,,False
cbc100f9459ee41fa74a2ef65540097e420a461f,PMC,"Study of the effect on shelter cat intakes and euthanasia from a shelter neuter return project of 10,080 cats from March 2010 to June 2014",http://dx.doi.org/10.7717/peerj.646,PMC4217190,25374785,CC BY,"Cat impoundments were increasing at the municipal San Jose animal shelter in 2009, despite long-term successful low cost sterilization programs and attempts to lower the euthanasia rate of treatable-rehabilitatable impounds beginning in 2008. San Jose Animal Care and Services implemented a new strategy designed to control overall feral cat reproduction by altering and returning feral cats entering the shelter system, rather than euthanizing the cats. The purpose of this case study was to determine how the program affected the shelter cat intakes over time. In just over four years, 10,080 individual healthy adult feral cats, out of 11,423 impounded at the shelter during this time frame, were altered and returned to their site of capture. Included in the 11,423 cats were 862 cats impounded from one to four additional times for a total of 958 (9.5%) recaptures of the previously altered 10,080 cats. The remaining 385 healthy feral cats were euthanized at the shelter from March 2010 to June 2014. Four years into the program, researchers observed cat and kitten impounds decreased 29.1%; euthanasia decreased from over 70% of intakes in 2009, to 23% in 2014. Euthanasia in the shelter for Upper Respiratory Disease decreased 99%; dead cat pick up off the streets declined 20%. Dog impounds did not similarly decline over the four years. No other laws or program changes were implemented since the beginning of the program.",2014 Oct 30,"['Johnson, Karen L.', 'Cicirelli, Jon']",PeerJ,,,True
dc4332792ad6c643b1142cef1d344755a64b9625,PMC,Factors Influencing the Measurement of Plasma/Serum Surfactant Protein D Levels by ELISA,http://dx.doi.org/10.1371/journal.pone.0111466,PMC4218753,25365324,CC0,"BACKGROUND: Extensive variations in human surfactant protein D (SP-D) levels in circulation as measured by ELISA exist in the published literature. In order to determine the source of these variations, factors influencing the measurement by ELISA were explored. MATERIALS AND METHODS: Peripheral blood from healthy individuals was collected into various vacutainers during the same blood draw. Recombinant SP-D was diluted into different matrices and used for a standard curve. Samples were analyzed by capture ELISA using one of two distinct detection antibodies. RESULTS: The type of matrix had some effects on detection of recombinant SP-D. The type of anticoagulant used and dilution factor had very little effect, except for in plasma collected in EDTA vacutainers. The extent of variation in published values seemed to be due to the ELISA configuration employed, and, in agreement with this, we found that by switching the detection antibody, there was a 50% decrease in the extrapolated SP-D value of serum and plasma samples. Storage of samples resulted in slight changes in measured SP-D levels. CONCLUSIONS: The ELISA configuration employed to measure circulating levels of SP-D has a significant effect on the extrapolated values. In both configurations tested, the use of EDTA as a coagulant resulted in inconsistent values, and we, therefore, suggest the avoidance of this anticoagulant when assaying for SP-D by ELISA. While the demonstrated effects of several factors on measurement of SP-D may not account for all the disparities amongst the previous studies, they stress that variations in methodologies for measuring the same protein can result in very inconsistent results.",2014 Nov 3,"['Bratcher, Preston E.', 'Gaggar, Amit']",PLoS One,,,True
ac52347e640db03cb8dfaf1f0228caf47570ddaa,PMC,Patient-Based Transcriptome-Wide Analysis Identify Interferon and Ubiquination Pathways as Potential Predictors of Influenza A Disease Severity,http://dx.doi.org/10.1371/journal.pone.0111640,PMC4218794,25365328,CC BY,"BACKGROUND: The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500,000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged >65 years, infants, pregnant women, and individuals of any age with underlying health conditions. METHODOLOGY/PRINCIPAL FINDINGS: Using gene expression microarrays, the transcriptomic profiles of influenza-infected patients with severe (N = 11), moderate (N = 40) and mild (N = 83) symptoms were compared with the febrile patients of unknown etiology (N = 73). We found that influenza-infected patients, regardless of their clinical outcomes, had a stronger induction of antiviral and cytokine responses and a stronger attenuation of NK and T cell responses in comparison with those with unknown etiology. More importantly, we found that both interferon and ubiquitination signaling were strongly attenuated in patients with the most severe outcomes in comparison with those with moderate and mild outcomes, suggesting the protective roles of these pathways in disease pathogenesis. CONCLUSION/SIGNIFICANCES: The attenuation of interferon and ubiquitination pathways may associate with the clinical outcomes of influenza patients.",2014 Nov 3,"['Hoang, Long Truong', 'Tolfvenstam, Thomas', 'Ooi, Eng Eong', 'Khor, Chiea Chuen', 'Naim, Ahmand Nazri Mohamed', 'Ho, Eliza Xin Pei', 'Ong, Swee Hoe', 'Wertheim, Heiman F.', 'Fox, Annette', 'Van Vinh Nguyen, Chau', 'Nghiem, Ngoc My', 'Ha, Tuan Manh', 'Thi Ngoc Tran, Anh', 'Tambayah, Paul', 'Lin, Raymond', 'Sangsajja, Chariya', 'Manosuthi, Weerawat', 'Chuchottaworn, Chareon', 'Sansayunh, Piamlarp', 'Chotpitayasunondh, Tawee', 'Suntarattiwong, Piyarat', 'Chokephaibulkit, Kulkanya', 'Puthavathana, Pilaipan', 'de Jong, Menno D.', 'Farrar, Jeremy', 'van Doorn, H. Rogier', 'Hibberd, Martin Lloyd']",PLoS One,,,True
e0f36613dbfcdb38aee79337d0a011c8760acba0,PMC,"Antibodies against H10N8 avian influenza virus among animal workers in Guangdong Province before November 30, 2013, when the first human H10N8 case was recognized",http://dx.doi.org/10.1186/s12916-014-0205-3,PMC4219099,25348464,CC BY,"BACKGROUND: Considered an epicenter of pandemic influenza virus generation, southern China has recently seen an increasing number of human H7N9 infections. However, it is not the only threat. On 30 November 2013, a human H10N8 infection case was first described in China. The origin and genetic diversity of this novel virus is similar to that of H7N9 virus. As H10N8 avian influenza virus (AIV) was first identified from a duck in Guangdong Province during 2012 and there is also evidence of H10N8 infected dogs in this region, we sought to examine archived sera from animal workers to see if there was evidence of subclinical human infections before the first human H10N8 cases. METHODS: We studied archived serum samples (cross-sectional study, convenience sample) collected between May and September 2013 from 710 animal workers and 107 non-animal exposed volunteers living in five cities of Guangdong Province. Study participants’ sera were tested by horse red blood cells (RBCs) hemagglutination inhibition (HI) and microneutralization (MN) assays according to World Health Organization guidelines. The A/Jiangxi-Donghu/346-1/2013(H10N8) virus was used. Sera which have an HI assay ≥1:20 were further tested with the MN assay. Questionnaire data were examined for risk factor associations with positive serological assays. Risk factor analyses failed to identify specific factors associated with probable H10N8 infections. RESULTS: Among the 827 sera, only 21 animal workers had an HI titer ≥1:20 (18 had an HI titer of 1:20 and 3 had an HI titer of 1:40). None of these 21 subjects reported experiencing any influenza symptoms during the three months before enrollment. Among the three subjects with HI titers of 1:40, two had MN antibody titers of 1:40, and one had a MN antibody titer of 1:80 (probable H10N8 infections). CONCLUSIONS: Study data suggest that animal workers may have been infected with the H10N8 virus before the first recognized H10N8 human infection cases. It seems prudent to continue surveillance for H10N8 viruses among animal workers.",2014 Oct 27,"['Qi, Wenbao', 'Su, Shuo', 'Xiao, Chencheng', 'Zhou, Pei', 'Li, Huanan', 'Ke, Changwen', 'Gray, Gregory C', 'Zhang, Guihong', 'Liao, Ming']",BMC Med,,,True
5eba29203084de16f501b71b64873f5c96ce55f2,PMC,Toll-Like Receptor Responses to Peste des petits ruminants Virus in Goats and Water Buffalo,http://dx.doi.org/10.1371/journal.pone.0111609,PMC4219731,25369126,CC BY,"Ovine rinderpest or goat plague is an economically important and contagious viral disease of sheep and goats, caused by the Peste des petits ruminants virus (PPRV). Differences in susceptibility to goat plague among different breeds and water buffalo exist. The host innate immune system discriminates between pathogen associated molecular patterns and self antigens through surveillance receptors known as Toll like receptors (TLR). We investigated the role of TLR and cytokines in differential susceptibility of goat breeds and water buffalo to PPRV. We examined the replication of PPRV in peripheral blood mononuclear cells (PBMC) of Indian domestic goats and water buffalo and demonstrated that the levels of TLR3 and TLR7 and downstream signalling molecules correlation with susceptibility vs resistance. Naturally susceptible goat breeds, Barbari and Tellichery, had dampened innate immune responses to PPRV and increased viral loads with lower basal expression levels of TLR 3/7. Upon stimulation of PBMC with synthetic TLR3 and TLR7 agonists or PPRV, the levels of proinflammatory cytokines were found to be significantly higher while immunosuppressive interleukin (IL) 10 levels were lower in PPRV resistant Kanni and Salem Black breeds and water buffalo at transcriptional level, correlating with reduced viralloads in infected PBMC. Water buffalo produced higher levels of interferon (IFN) α in comparison with goats at transcriptional and translational levels. Pre-treatment of Vero cells with human IFNα resulted in reduction of PPRV replication, confirming the role of IFNα in limiting PPRV replication. Treatment with IRS66, a TLR7 antagonist, resulted in the reduction of IFNα levels, with increased PPRV replication confirming the role of TLR7. Single nucleotide polymorphism analysis of TLR7 of these goat breeds did not show any marked nucleotide differences that might account for susceptibility vs resistance to PPRV. Analyzing other host genetic factors might provide further insights on susceptibility to PPRV and genetic polymorphisms in the host.",2014 Nov 4,"['Dhanasekaran, Sakthivel', 'Biswas, Moanaro', 'Vignesh, Ambothi R.', 'Ramya, R.', 'Raj, Gopal Dhinakar', 'Tirumurugaan, Krishnaswamy G.', 'Raja, Angamuthu', 'Kataria, Ranjit S.', 'Parida, Satya', 'Subbiah, Elankumaran']",PLoS One,,,True
ff7d7dea55e89908b0a3935c6e5ce52cd8a165b4,PMC,Immunomodulatory Potential of Human Adipose Mesenchymal Stem Cells Derived Exosomes on in vitro Stimulated T Cells,http://dx.doi.org/10.3389/fimmu.2014.00556,PMC4220146,25414703,CC BY,"In the recent years, it has been demonstrated that the biological activity of mesenchymal stem cells (MSCs) is mediated through the release of paracrine factors. Many of these factors are released into exosomes, which are small membranous vesicles that participate in cell–cell communication. Exosomes from MSCs are thought to have similar functions to MSCs such as repairing and regeneration of damaged tissue, but little is known about the immunomodulatory effect of these vesicles. Based on an extensive bibliography where the immunomodulatory capacity of MSCs has been demonstrated, here we hypothesized that released exosomes from MSCs may have an immunomodulatory role on the differentiation, activation and function of different lymphocyte subsets. According to this hypothesis, in vitro experiments were performed to characterize the immunomodulatory effect of human adipose MSCs derived exosomes (exo-hASCs) on in vitro stimulated T cells. The phenotypic characterization of cytotoxic and helper T cells (activation and differentiation markers) together with functional assays (proliferation and IFN-γ production) demonstrated that exo-hASCs exerted an inhibitory effect in the differentiation and activation of T cells as well as a reduced T cell proliferation and IFN-γ release on in vitro stimulated cells. In summary, here we demonstrate that MSCs-derived exosomes are a cell-derived product that could be considered as a therapeutic agent for the treatment of inflammation-related diseases.",2014 Nov 4,"['Blazquez, Rebeca', 'Sanchez-Margallo, Francisco Miguel', 'de la Rosa, Olga', 'Dalemans, Wilfried', 'Álvarez, Verónica', 'Tarazona, Raquel', 'Casado, Javier G.']",Front Immunol,,,True
ae098292360fde9d65ff12d2beef927dff6c6077,PMC,Containing the accidental laboratory escape of potential pandemic influenza viruses,http://dx.doi.org/10.1186/1741-7015-11-252,PMC4220800,24283203,CC BY,"BACKGROUND: The recent work on the modified H5N1 has stirred an intense debate on the risk associated with the accidental release from biosafety laboratory of potential pandemic pathogens. Here, we assess the risk that the accidental escape of a novel transmissible influenza strain would not be contained in the local community. METHODS: We develop here a detailed agent-based model that specifically considers laboratory workers and their contacts in microsimulations of the epidemic onset. We consider the following non-pharmaceutical interventions: isolation of the laboratory, laboratory workers’ household quarantine, contact tracing of cases and subsequent household quarantine of identified secondary cases, and school and workplace closure both preventive and reactive. RESULTS: Model simulations suggest that there is a non-negligible probability (5% to 15%), strongly dependent on reproduction number and probability of developing clinical symptoms, that the escape event is not detected at all. We find that the containment depends on the timely implementation of non-pharmaceutical interventions and contact tracing and it may be effective (>90% probability per event) only for pathogens with moderate transmissibility (reproductive number no larger than R(0) = 1.5). Containment depends on population density and structure as well, with a probability of giving rise to a global event that is three to five times lower in rural areas. CONCLUSIONS: Results suggest that controllability of escape events is not guaranteed and, given the rapid increase of biosafety laboratories worldwide, this poses a serious threat to human health. Our findings may be relevant to policy makers when designing adequate preparedness plans and may have important implications for determining the location of new biosafety laboratories worldwide.",2013 Nov 28,"['Merler, Stefano', 'Ajelli, Marco', 'Fumanelli, Laura', 'Vespignani, Alessandro']",BMC Med,,,True
a9be3897c30e4a416d00398d86a623fc3d9faab5,PMC,Containing the accidental laboratory escape of potential pandemic influenza viruses,http://dx.doi.org/10.1186/1741-7015-11-252,PMC4220800,24283203,CC BY,"BACKGROUND: The recent work on the modified H5N1 has stirred an intense debate on the risk associated with the accidental release from biosafety laboratory of potential pandemic pathogens. Here, we assess the risk that the accidental escape of a novel transmissible influenza strain would not be contained in the local community. METHODS: We develop here a detailed agent-based model that specifically considers laboratory workers and their contacts in microsimulations of the epidemic onset. We consider the following non-pharmaceutical interventions: isolation of the laboratory, laboratory workers’ household quarantine, contact tracing of cases and subsequent household quarantine of identified secondary cases, and school and workplace closure both preventive and reactive. RESULTS: Model simulations suggest that there is a non-negligible probability (5% to 15%), strongly dependent on reproduction number and probability of developing clinical symptoms, that the escape event is not detected at all. We find that the containment depends on the timely implementation of non-pharmaceutical interventions and contact tracing and it may be effective (>90% probability per event) only for pathogens with moderate transmissibility (reproductive number no larger than R(0) = 1.5). Containment depends on population density and structure as well, with a probability of giving rise to a global event that is three to five times lower in rural areas. CONCLUSIONS: Results suggest that controllability of escape events is not guaranteed and, given the rapid increase of biosafety laboratories worldwide, this poses a serious threat to human health. Our findings may be relevant to policy makers when designing adequate preparedness plans and may have important implications for determining the location of new biosafety laboratories worldwide.",2013 Nov 28,"['Merler, Stefano', 'Ajelli, Marco', 'Fumanelli, Laura', 'Vespignani, Alessandro']",BMC Med,,,True
59af69dc1c698ba1b34d45b5a2e84302f0c1a907,PMC,MERS-CoV,http://dx.doi.org/10.1186/1471-2334-14-S2-S22,PMC4221070,,CC BY,,2014 May 23,"Müller, Marcel A",BMC Infect Dis,,,False
d0cb4b695a1cddbc249dcc8cb517441dea0157d6,PMC,Achieving compliance with the International Health Regulations by overseas territories of the United Kingdom of Great Britain and Northern Ireland,http://dx.doi.org/10.2471/BLT.14.137828,PMC4221769,25378745,CC BY,"The 2005 International Health Regulations (IHR) came into force for all Member States of the World Health Organization (WHO) in June 2007 and the deadline for achieving compliance was June 2012. The purpose of the IHR is to prevent, protect against, control – and provide a public health response to – international spread of disease. The territory of the United Kingdom of Great Britain and Northern Ireland and that of several other Member States, such as China, Denmark, France, the Netherlands and the United States of America, include overseas territories, which cover a total population of approximately 15 million people. Member States have a responsibility to ensure that all parts of their territory comply with the IHR. Since WHO has not provided specific guidance on compliance in the special circumstances of the overseas territories of Member States, compliance by these territories is an issue for self-assessment by Member States themselves. To date, no reports have been published on the assessment of IHR compliance in countries with overseas territories. We describe a gap analysis done in the United Kingdom to assess IHR compliance of its overseas territories. The findings and conclusions are broadly applicable to other countries with overseas territories which may have yet to assess their compliance with the IHR. Such assessments are needed to ensure compliance across all parts of a Member States’ territory and to increase global health security.",2014 Nov 1,"['Hamblion, Esther L', 'Salter, Mark', 'Jones, Jane', None]",Bull World Health Organ,,,True
64adce98190f9491944dc9d5141e0cccb6360519,PMC,Type I Interferon Regulates the Expression of Long Non-Coding RNAs,http://dx.doi.org/10.3389/fimmu.2014.00548,PMC4222131,25414701,CC BY,"Interferons (IFNs) are key players in the antiviral response. IFN sensing by the cell activates transcription of IFN-stimulated genes (ISGs) able to induce an antiviral state by affecting viral replication and release. IFN also induces the expression of ISGs that function as negative regulators to limit the strength and duration of IFN response. The ISGs identified so far belong to coding genes. However, only a small proportion of the transcriptome corresponds to coding transcripts and it has been estimated that there could be as many coding as long non-coding RNAs (lncRNAs). To address whether IFN can also regulate the expression of lncRNAs, we analyzed the transcriptome of HuH7 cells treated or not with IFNα2 by expression arrays. Analysis of the arrays showed increased levels of several well-characterized coding genes that respond to IFN both at early or late times. Furthermore, we identified several IFN-stimulated or -downregulated lncRNAs (ISRs and IDRs). Further validation showed that ISR2, 8, and 12 expression mimics that of their neighboring genes GBP1, IRF1, and IL6, respectively, all related to the IFN response. These genes are induced in response to different doses of IFNα2 in different cell lines at early (ISR2 or 8) or later (ISR12) time points. IFNβ also induced the expression of these lncRNAs. ISR2 and 8 were also induced by an influenza virus unable to block the IFN response but not by other wild-type lytic viruses tested. Surprisingly, both ISR2 and 8 were significantly upregulated in cultured cells and livers from patients infected with HCV. Increased levels of ISR2 were also detected in patients chronically infected with HIV. This is relevant as genome-wide guilt-by-association studies predict that ISR2, 8, and 12 may function in viral processes, in the IFN pathway and the antiviral response. Therefore, we propose that these lncRNAs could be induced by IFN to function as positive or negative regulators of the antiviral response.",2014 Nov 6,"['Carnero, Elena', 'Barriocanal, Marina', 'Segura, Victor', 'Guruceaga, Elizabeth', 'Prior, Celia', 'Börner, Kathleen', 'Grimm, Dirk', 'Fortes, Puri']",Front Immunol,,,True
538d34ee99bf5a6c75bc18a2749e0aff5ce72d35,PMC,Patterns of between-farm contacts via professionals in Sweden,http://dx.doi.org/10.1186/s13028-014-0070-2,PMC4222379,25366065,CC BY,"BACKGROUND: Infectious diseases of livestock have negative consequences for animal production as well as animal health and welfare and can be transmitted between farms via direct (live animal movements) as well as indirect (via physical vectors such as, people, transport vehicles and fomites) contacts. The objective of the study was to examine the travel patterns of professionals visiting Swedish farms (veterinarians, milk tanker drivers, artificial inseminators, maintenance technicians and livestock hauliers). This was done by obtaining records of the farms visited by a sample of professionals in the above categories in one week in January, one week in April, one week in July and one week in October in the Swedish counties Västerbotten, Södermanland, Västergötland and Skåne. RESULTS: There were twelve participating organisations, and data was provided for one to three individuals/vehicles/veterinary practices per professional category and per geographic region (except for dairy service technicians and livestock hauliers who did not provide data from all regions). There was a trend towards larger areas covered and smaller number of farms visited per week in the north, but exceptions occurred and there were regional variations. Generally, the greatest areas were travelled by milk tankers and livestock hauliers, and the profession travelling over the smallest areas tended to be the veterinarians. Milk tankers visited most farms per week, one milk tanker could visit between 23 and 90 farms per week and travel over areas between 717 km(2) and 23,512 km(2) per week. CONCLUSIONS: Valuable insight into the travel patterns of Swedish professionals has emerged although the implications of the study largely concern highly infectious diseases. Movement of live animals pose the greatest risk for the spread of infectious animal diseases; however indirect contacts are important for many diseases. The results of this study indicate that in Sweden a highly contagious disease might spread over a large area in the time span of one incubation period, which ought to be kept in mind in case of an outbreak and in outbreak investigations. The difficulties in contacting some professionals visiting farms could be a problem in an outbreak situation.",2014 Nov 4,"['Olofsson, Emelie', 'Nöremark, Maria', 'Lewerin, Susanna Sternberg']",Acta Vet Scand,,,True
d1465b112750748b01edc7837f005803a6e87658,PMC,Escherichia coli YmdB regulates biofilm formation independently of its role as an RNase III modulator,http://dx.doi.org/10.1186/1471-2180-13-266,PMC4222554,24267348,CC BY,"BACKGROUND: Ribonuclease III (RNase III) activity modulates hundreds of genes in Escherichia coli (E. coli). YmdB, a member of the macrodomain protein family, is one of known trans-acting regulators of RNase III activity; however, the significance of its regulatory role in specific bacterial cellular processes and related genes has not been determined. YmdB overexpression was used to model YmdB-induced RNase III inhibition in vivo, and microarray analysis identified gene targets and cellular processes related to RNase III inhibition. RESULTS: The expression of >2,000 E. coli genes was modulated by YmdB induction; 129 genes were strongly regulated, of which 80 have not been reported as RNase III targets. Of these, ten are involved in biofilm formation. Significantly, YmdB overexpression also inhibited biofilm formation via a process that is not uniquely dependent upon RNase III inhibition. Moreover, biofilm formation is interdependently regulated by RpoS, a known stress response regulator and biofilm inhibitor, and by YmdB. CONCLUSIONS: This is the first global profile of target genes modulated by YmdB-induced RNase III inhibition in E. coli, and the data reveal a novel, hitherto unrecognized regulatory role for YmdB in biofilm modulation.",2013 Nov 24,"['Kim, Taeyeon', 'Lee, Juyeon', 'Kim, Kwang-sun']",BMC Microbiol,,,True
a1cc5852e148a66c7044a68bef5d6e9323fb4a99,PMC,Escherichia coli YmdB regulates biofilm formation independently of its role as an RNase III modulator,http://dx.doi.org/10.1186/1471-2180-13-266,PMC4222554,24267348,CC BY,"BACKGROUND: Ribonuclease III (RNase III) activity modulates hundreds of genes in Escherichia coli (E. coli). YmdB, a member of the macrodomain protein family, is one of known trans-acting regulators of RNase III activity; however, the significance of its regulatory role in specific bacterial cellular processes and related genes has not been determined. YmdB overexpression was used to model YmdB-induced RNase III inhibition in vivo, and microarray analysis identified gene targets and cellular processes related to RNase III inhibition. RESULTS: The expression of >2,000 E. coli genes was modulated by YmdB induction; 129 genes were strongly regulated, of which 80 have not been reported as RNase III targets. Of these, ten are involved in biofilm formation. Significantly, YmdB overexpression also inhibited biofilm formation via a process that is not uniquely dependent upon RNase III inhibition. Moreover, biofilm formation is interdependently regulated by RpoS, a known stress response regulator and biofilm inhibitor, and by YmdB. CONCLUSIONS: This is the first global profile of target genes modulated by YmdB-induced RNase III inhibition in E. coli, and the data reveal a novel, hitherto unrecognized regulatory role for YmdB in biofilm modulation.",2013 Nov 24,"['Kim, Taeyeon', 'Lee, Juyeon', 'Kim, Kwang-sun']",BMC Microbiol,,,False
e47f91345fe98307b49fc5f39aa5f781ec37f893,PMC,Specificity and Effector Functions of Human RSV-Specific IgG from Bovine Milk,http://dx.doi.org/10.1371/journal.pone.0112047,PMC4222812,25375837,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) infection is the second most important cause of death in the first year of life, and early RSV infections are associated with the development of asthma. Breastfeeding and serum IgG have been shown to protect against RSV infection. Yet, many infants depend on bovine milk-based nutrition, which at present lacks intact immunoglobulins. OBJECTIVE: To investigate whether IgG purified from bovine milk (bIgG) can modulate immune responses against human RSV. METHODS: ELISAs were performed to analyse binding of bIgG to human respiratory pathogens. bIgG or hRSV was coated to plates to assess dose-dependent binding of bIgG to human Fcγ receptors (FcγR) or bIgG-mediated binding of myeloid cells to hRSV respectively. S. Epidermidis and RSV were used to test bIgG-mediated binding and internalisation of pathogens by myeloid cells. Finally, the ability of bIgG to neutralise infection of HEp2 cells by hRSV was evaluated. RESULTS: bIgG recognised human RSV, influenza haemagglutinin and Haemophilus influenza. bIgG bound to FcγRII on neutrophils, monocytes and macrophages, but not to FcγRI and FcγRIII, and could bind simultaneously to hRSV and human FcγRII on neutrophils. In addition, human neutrophils and dendritic cells internalised pathogens that were opsonised with bIgG. Finally, bIgG could prevent infection of HEp2 cells by hRSV. CONCLUSIONS: The data presented here show that bIgG binds to hRSV and other human respiratory pathogens and induces effector functions through binding to human FcγRII on phagocytes. Thus bovine IgG may contribute to immune protection against RSV.",2014 Nov 6,"['den Hartog, Gerco', 'Jacobino, Shamir', 'Bont, Louis', 'Cox, Linda', 'Ulfman, Laurien H.', 'Leusen, Jeanette H. W.', 'van Neerven, R. J. Joost']",PLoS One,,,True
2c33d7f0e90a4a8a7e7be1d56308496b7e13dad5,PMC,"Symptomatic treatment of the common cold with a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine: a randomized, placebo-controlled trial",http://dx.doi.org/10.1186/1471-2334-13-556,PMC4222817,24261438,CC BY,"BACKGROUND: The common cold and other viral airway infections are highly prevalent in the population, and their treatment often requires the use of medications for symptomatic relief. Paracetamol is as an analgesic and antipyretic; chlorphenamine is an antihistamine; and phenylephrine, a vasoconstrictor and decongestant. This randomized, double-blind, placebo-controlled trial sought to evaluate the efficacy and safety of a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine in the symptomatic treatment of the common cold and flu-like syndrome in adults. METHODS: This study enrolled 146 individuals aged 18 to 60 years who had moderate to severe flu-like syndrome or common cold. After clinical examination and laboratory tests, individuals were randomly assigned to receive the fixed-dose combination (73) or placebo (73), five capsules per day for 48 to 72 hours. The primary efficacy endpoint was the sum of the scores of 10 symptoms on a four-point Likert-type scale. To evaluate treatment safety, the occurrence of adverse events was also measured. RESULTS: Mean age was 33.5 (±9.5) years in the placebo group and 33.8 (±11.5) in the treatment group. There were 55 women and 18 men in the placebo group, and 46 women and 27 men in the treatment group. Comparison of overall symptom scores in the two groups revealed a significantly greater reduction in the treatment group than in the placebo group (p = 0.015). Analysis at the first 13 dose intervals (± 66 h of treatment) showed a greater reduction of symptom scores in the treatment group than in the placebo group (p < 0.05). The number and distribution of adverse events were similar in both groups. CONCLUSION: A fixed-dose combination of paracetamol, chlorphenamine and phenylephrine was safe and more effective than placebo in the symptomatic treatment of the common cold or flu-like syndrome in adults. TRIAL REGISTRATION: NCT01389518",2013 Nov 22,"['Picon, Paulo Dornelles', 'Costa, Marisa Boff', 'da Veiga Picon, Rafael', 'Fendt, Lucia Costa Cabral', 'Suksteris, Maurício Leichter', 'Saccilotto, Indara Carmanim', 'Dornelles, Alicia Dorneles', 'Schmidt, Luis Felipe Carissimi']",BMC Infect Dis,,,True
e5ca488c67d3b9db4056f7fe900e10254d69f7ca,PMC,The Evolution and Genetics of Virus Host Shifts,http://dx.doi.org/10.1371/journal.ppat.1004395,PMC4223060,25375777,CC BY,"Emerging viral diseases are often the product of a host shift, where a pathogen jumps from its original host into a novel species. Phylogenetic studies show that host shifts are a frequent event in the evolution of most pathogens, but why pathogens successfully jump between some host species but not others is only just becoming clear. The susceptibility of potential new hosts can vary enormously, with close relatives of the natural host typically being the most susceptible. Often, pathogens must adapt to successfully infect a novel host, for example by evolving to use different cell surface receptors, to escape the immune response, or to ensure they are transmitted by the new host. In viruses there are often limited molecular solutions to achieve this, and the same sequence changes are often seen each time a virus infects a particular host. These changes may come at a cost to other aspects of the pathogen's fitness, and this may sometimes prevent host shifts from occurring. Here we examine how these evolutionary factors affect patterns of host shifts and disease emergence.",2014 Nov 6,"['Longdon, Ben', 'Brockhurst, Michael A.', 'Russell, Colin A.', 'Welch, John J.', 'Jiggins, Francis M.']",PLoS Pathog,,,True
3339f4bb346bfa3070ae5fc7dc745ef051535b0e,PMC,Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner,http://dx.doi.org/10.1371/journal.ppat.1004502,PMC4223067,25375324,CC BY,"Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell. While some viruses fuse with the plasma membrane, many viruses are endocytosed prior to fusion. Specific cues in the endosomal microenvironment induce conformational changes in the viral fusion proteins leading to viral and host membrane fusion. In the present study we investigated the entry of coronaviruses (CoVs). Using siRNA gene silencing, we found that proteins known to be important for late endosomal maturation and endosome-lysosome fusion profoundly promote infection of cells with mouse hepatitis coronavirus (MHV). Using recombinant MHVs expressing reporter genes as well as a novel, replication-independent fusion assay we confirmed the importance of clathrin-mediated endocytosis and demonstrated that trafficking of MHV to lysosomes is required for fusion and productive entry to occur. Nevertheless, MHV was shown to be less sensitive to perturbation of endosomal pH than vesicular stomatitis virus and influenza A virus, which fuse in early and late endosomes, respectively. Our results indicate that entry of MHV depends on proteolytic processing of its fusion protein S by lysosomal proteases. Fusion of MHV was severely inhibited by a pan-lysosomal protease inhibitor, while trafficking of MHV to lysosomes and processing by lysosomal proteases was no longer required when a furin cleavage site was introduced in the S protein immediately upstream of the fusion peptide. Also entry of feline CoV was shown to depend on trafficking to lysosomes and processing by lysosomal proteases. In contrast, MERS-CoV, which contains a minimal furin cleavage site just upstream of the fusion peptide, was negatively affected by inhibition of furin, but not of lysosomal proteases. We conclude that a proteolytic cleavage site in the CoV S protein directly upstream of the fusion peptide is an essential determinant of the intracellular site of fusion.",2014 Nov 6,"['Burkard, Christine', 'Verheije, Monique H.', 'Wicht, Oliver', 'van Kasteren, Sander I.', 'van Kuppeveld, Frank J.', 'Haagmans, Bart L.', 'Pelkmans, Lucas', 'Rottier, Peter J. M.', 'Bosch, Berend Jan', 'de Haan, Cornelis A. M.']",PLoS Pathog,,,True
9faf9327f699f47d3a08625a86ee07af1402f3c5,PMC,Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner,http://dx.doi.org/10.1371/journal.ppat.1004502,PMC4223067,25375324,CC BY,"Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell. While some viruses fuse with the plasma membrane, many viruses are endocytosed prior to fusion. Specific cues in the endosomal microenvironment induce conformational changes in the viral fusion proteins leading to viral and host membrane fusion. In the present study we investigated the entry of coronaviruses (CoVs). Using siRNA gene silencing, we found that proteins known to be important for late endosomal maturation and endosome-lysosome fusion profoundly promote infection of cells with mouse hepatitis coronavirus (MHV). Using recombinant MHVs expressing reporter genes as well as a novel, replication-independent fusion assay we confirmed the importance of clathrin-mediated endocytosis and demonstrated that trafficking of MHV to lysosomes is required for fusion and productive entry to occur. Nevertheless, MHV was shown to be less sensitive to perturbation of endosomal pH than vesicular stomatitis virus and influenza A virus, which fuse in early and late endosomes, respectively. Our results indicate that entry of MHV depends on proteolytic processing of its fusion protein S by lysosomal proteases. Fusion of MHV was severely inhibited by a pan-lysosomal protease inhibitor, while trafficking of MHV to lysosomes and processing by lysosomal proteases was no longer required when a furin cleavage site was introduced in the S protein immediately upstream of the fusion peptide. Also entry of feline CoV was shown to depend on trafficking to lysosomes and processing by lysosomal proteases. In contrast, MERS-CoV, which contains a minimal furin cleavage site just upstream of the fusion peptide, was negatively affected by inhibition of furin, but not of lysosomal proteases. We conclude that a proteolytic cleavage site in the CoV S protein directly upstream of the fusion peptide is an essential determinant of the intracellular site of fusion.",2014 Nov 6,"['Burkard, Christine', 'Verheije, Monique H.', 'Wicht, Oliver', 'van Kasteren, Sander I.', 'van Kuppeveld, Frank J.', 'Haagmans, Bart L.', 'Pelkmans, Lucas', 'Rottier, Peter J. M.', 'Bosch, Berend Jan', 'de Haan, Cornelis A. M.']",PLoS Pathog,,,False
96456a955d56878dc1e53c0feeb14bf307518b17,PMC,Programmed Ribosomal Frameshift Alters Expression of West Nile Virus Genes and Facilitates Virus Replication in Birds and Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004447,PMC4223154,25375107,CC0,"West Nile virus (WNV) is a human pathogen of significant medical importance with close to 40,000 cases of encephalitis and more than 1,600 deaths reported in the US alone since its first emergence in New York in 1999. Previous studies identified a motif in the beginning of non-structural gene NS2A of encephalitic flaviviruses including WNV which induces programmed −1 ribosomal frameshift (PRF) resulting in production of an additional NS protein NS1′. We have previously demonstrated that mutant WNV with abolished PRF was attenuated in mice. Here we have extended our previous observations by showing that PRF does not appear to have a significant role in virus replication, virion formation, and viral spread in several cell lines in vitro. However, we have also shown that PRF induces an over production of structural proteins over non-structural proteins in virus-infected cells and that mutation abolishing PRF is present in ∼11% of the wild type virus population. In vivo experiments in house sparrows using wild type and PRF mutant of New York 99 strain of WNV viruses showed some attenuation for the PRF mutant virus. Moreover, PRF mutant of Kunjin strain of WNV showed significant decrease compared to wild type virus infection in dissemination of the virus from the midgut through the haemocoel, and ultimately the capacity of infected mosquitoes to transmit virus. Thus our results demonstrate an important role for PRF in regulating expression of viral genes and consequently virus replication in avian and mosquito hosts.",2014 Nov 6,"['Melian, Ezequiel Balmori', 'Hall-Mendelin, Sonja', 'Du, Fangyao', 'Owens, Nick', 'Bosco-Lauth, Angela M.', 'Nagasaki, Tomoko', 'Rudd, Stephen', 'Brault, Aaron C.', 'Bowen, Richard A.', 'Hall, Roy A.', 'van den Hurk, Andrew F.', 'Khromykh, Alexander A.']",PLoS Pathog,,,True
9484a7c6359d1364cd37bb1d80bdefd118d7ffe6,PMC,Viruses and viral proteins,http://dx.doi.org/10.1107/S205225251402003X,PMC4224467,25485129,CC BY,"For more than 30 years X-ray crystallography has been by far the most powerful approach for determining the structures of viruses and viral proteins at atomic resolution. The information provided by these structures, which covers many important aspects of the viral life cycle such as cell-receptor recognition, viral entry, nucleic acid transfer and genome replication, has extensively enriched our vision of the virus world. Many of the structures available correspond to potential targets for antiviral drugs against important human pathogens. This article provides an overview of the current knowledge of different structural aspects of the above-mentioned processes.",2014 Oct 14,"['Verdaguer, Nuria', 'Ferrero, Diego', 'Murthy, Mathur R. N.']",IUCrJ,,,True
6086be90c6e06e3fcbef307a61c0563e029ee24d,PMC,Bordetella pertussis in infants hospitalized for acute respiratory symptoms remains a concern,http://dx.doi.org/10.1186/1471-2334-13-526,PMC4226035,24209790,CC BY,"BACKGROUND: Preliminary results suggest that pertussis infection might be considered in infants during a seasonal respiratory syncytial virus (RSV) outbreak. METHODS: In order to analyze clinical features and laboratory findings in infants with pertussis hospitalized for acute respiratory symptoms during a seasonal RSV outbreak, we conducted a retrospective single-center study on 19 infants with pertussis (6 boys; median age 72 days) and 19 matched controls (RSV-bronchiolitis), hospitalized from October 2008 to April 2010. B. pertussis and RSV were detected from nasopharyngeal washes with Real Time-PCR. RESULTS: Infants with pertussis were less often breastfeed than infants with RSV bronchiolitis (63.2% vs 89.5%; p <0.06). Clinically, significantly fewer infants with pertussis than controls had more episodes of whooping cough (63.2% vs 0.0%; p < 0.001) and also less frequently fever at admission (15.8% vs 68.4%; p <0.01), apnea (52.6% vs 10.5%; p <0.006), and cyanosis (52.6% vs 10.5%; p < 0.006). Infants with pertussis had more often no abnormal chest sounds on auscultation than infants with RSV bronchiolitis (0% vs 42,1%; p < 0.005). The absolute blood lymphocyte and eosinophil counts were higher in infants with B. pertussis than in controls with bronchiolitis (23886 ± 16945 vs 10725 ± 4126 cells/mm(3), p < 0.0001 and 13.653 ± 10.430 vs 4.730 ± 2.400 cells/mm(3), p < 0.001). The molecular analysis of 2 B. pertussis isolates for ptxA1, ptxP3, and prn2 genes showed the presence of gene variants. CONCLUSIONS: When infants are hospitalized for acute respiratory symptoms, physicians should suspect a pertussis infection, seek for specific clinical symptoms, investigate lymphocyte and eosinophil counts and thus diagnose infection early enough to allow treatment.",2013 Nov 8,"['Nicolai, Ambra', 'Nenna, Raffaella', 'Stefanelli, Paola', 'Carannante, Anna', 'Schiavariello, Concetta', 'Pierangeli, Alessandra', 'Scagnolari, Carolina', 'Moretti, Corrado', 'Papoff, Paola', 'Bonci, Enea', 'Ferrara, Marianna', 'Papasso, Stefano', 'Midulla, Fabio']",BMC Infect Dis,,,True
ab3cd83b4fa77a65b99102d3d9afcfe861bdb2c4,PMC,"Simulate_PCR for amplicon prediction and annotation from multiplex, degenerate primers and probes",http://dx.doi.org/10.1186/1471-2105-15-237,PMC4226945,25005023,CC BY,"BACKGROUND: Pairing up primers to amplify desired targets and avoid undesired cross reactions can be a combinatorial challenge. Effective prediction of specificity and inclusivity from multiplexed primers and TaqMan®/Luminex® probes is a critical step in PCR design. RESULTS: Code is described to identify all primer and probe combinations from a list of unpaired, unordered candidates that should produce a product. It predicts and extracts all amplicon sequences in a large sequence database from a list of primers and probes, allowing degenerate bases and user-specified levels of primer-target mismatch tolerance. Amplicons hit by TaqMan®/Luminex® probes are indicated, and products may be annotated with gene information from NCBI. Fragment length distributions are calculated to predict electrophoretic gel banding patterns. CONCLUSIONS: Simulate_PCR is the only freely available software that can be run from the command line for high throughput applications which can calculate all products from large lists of primers and probes compared to a large sequence database such as nt. It requires no prior knowledge of how primers should be paired. Degenerate bases are allowed and entire amplicon sequences are extracted and annotated with gene information. Examples are provided for sets of TaqMan®/Luminex® PCR signatures predicted to amplify all HIV-1 genomes, all Coronaviridae genomes, and a group of antibiotic resistance genes. The software is a command line perl script freely available as open source.",2014 Jul 9,"['Gardner, Shea N', 'Slezak, Tom']",BMC Bioinformatics,,,True
a3bf6f0444bb71c6d5b232122353d551a15d0a5f,PMC,Archaeal DnaG contains a conserved N-terminal RNA-binding domain and enables tailing of rRNA by the exosome,http://dx.doi.org/10.1093/nar/gku969,PMC4227792,25326320,CC BY,"The archaeal exosome is a phosphorolytic 3′–5′ exoribonuclease complex. In a reverse reaction it synthesizes A-rich RNA tails. Its RNA-binding cap comprises the eukaryotic orthologs Rrp4 and Csl4, and an archaea-specific subunit annotated as DnaG. In Sulfolobus solfataricus DnaG and Rrp4 but not Csl4 show preference for poly(rA). Archaeal DnaG contains N- and C-terminal domains (NTD and CTD) of unknown function flanking a TOPRIM domain. We found that the NT and TOPRIM domains have comparable, high conservation in all archaea, while the CTD conservation correlates with the presence of exosome. We show that the NTD is a novel RNA-binding domain with poly(rA)-preference cooperating with the TOPRIM domain in binding of RNA. Consistently, a fusion protein containing full-length Csl4 and NTD of DnaG led to enhanced degradation of A-rich RNA by the exosome. We also found that DnaG strongly binds native and in vitro transcribed rRNA and enables its polynucleotidylation by the exosome. Furthermore, rRNA-derived transcripts with heteropolymeric tails were degraded faster by the exosome than their non-tailed variants. Based on our data, we propose that archaeal DnaG is an RNA-binding protein, which, in the context of the exosome, is involved in targeting of stable RNA for degradation.",2014 Nov 10,"['Hou, Linlin', 'Klug, Gabriele', 'Evguenieva-Hackenberg, Elena']",Nucleic Acids Res,,,True
6056125fa915e5c43fae515aa0813c1583262f68,PMC,Archaeal DnaG contains a conserved N-terminal RNA-binding domain and enables tailing of rRNA by the exosome,http://dx.doi.org/10.1093/nar/gku969,PMC4227792,25326320,CC BY,"The archaeal exosome is a phosphorolytic 3′–5′ exoribonuclease complex. In a reverse reaction it synthesizes A-rich RNA tails. Its RNA-binding cap comprises the eukaryotic orthologs Rrp4 and Csl4, and an archaea-specific subunit annotated as DnaG. In Sulfolobus solfataricus DnaG and Rrp4 but not Csl4 show preference for poly(rA). Archaeal DnaG contains N- and C-terminal domains (NTD and CTD) of unknown function flanking a TOPRIM domain. We found that the NT and TOPRIM domains have comparable, high conservation in all archaea, while the CTD conservation correlates with the presence of exosome. We show that the NTD is a novel RNA-binding domain with poly(rA)-preference cooperating with the TOPRIM domain in binding of RNA. Consistently, a fusion protein containing full-length Csl4 and NTD of DnaG led to enhanced degradation of A-rich RNA by the exosome. We also found that DnaG strongly binds native and in vitro transcribed rRNA and enables its polynucleotidylation by the exosome. Furthermore, rRNA-derived transcripts with heteropolymeric tails were degraded faster by the exosome than their non-tailed variants. Based on our data, we propose that archaeal DnaG is an RNA-binding protein, which, in the context of the exosome, is involved in targeting of stable RNA for degradation.",2014 Nov 10,"['Hou, Linlin', 'Klug, Gabriele', 'Evguenieva-Hackenberg, Elena']",Nucleic Acids Res,,,False
08c1093aa1c393ee5364089d26278781dc3a3405,PMC,Mapping overlapping functional elements embedded within the protein-coding regions of RNA viruses,http://dx.doi.org/10.1093/nar/gku981,PMC4227794,25326325,CC BY,"Identification of the full complement of genes and other functional elements in any virus is crucial to fully understand its molecular biology and guide the development of effective control strategies. RNA viruses have compact multifunctional genomes that frequently contain overlapping genes and non-coding functional elements embedded within protein-coding sequences. Overlapping features often escape detection because it can be difficult to disentangle the multiple roles of the constituent nucleotides via mutational analyses, while high-throughput experimental techniques are often unable to distinguish functional elements from incidental features. However, RNA viruses evolve very rapidly so that, even within a single species, substitutions rapidly accumulate at neutral or near-neutral sites providing great potential for comparative genomics to distinguish the signature of purifying selection. Computationally identified features can then be efficiently targeted for experimental analysis. Here we analyze alignments of protein-coding virus sequences to identify regions where there is a statistically significant reduction in the degree of variability at synonymous sites, a characteristic signature of overlapping functional elements. Having previously tested this technique by experimental verification of discoveries in selected viruses, we now analyze sequence alignments for ∼700 RNA virus species to identify hundreds of such regions, many of which have not been previously described.",2014 Nov 10,"Firth, Andrew E.",Nucleic Acids Res,,,True
ed745dd99691994096cdc638c5398cd65a2c9539,PMC,Mapping overlapping functional elements embedded within the protein-coding regions of RNA viruses,http://dx.doi.org/10.1093/nar/gku981,PMC4227794,25326325,CC BY,"Identification of the full complement of genes and other functional elements in any virus is crucial to fully understand its molecular biology and guide the development of effective control strategies. RNA viruses have compact multifunctional genomes that frequently contain overlapping genes and non-coding functional elements embedded within protein-coding sequences. Overlapping features often escape detection because it can be difficult to disentangle the multiple roles of the constituent nucleotides via mutational analyses, while high-throughput experimental techniques are often unable to distinguish functional elements from incidental features. However, RNA viruses evolve very rapidly so that, even within a single species, substitutions rapidly accumulate at neutral or near-neutral sites providing great potential for comparative genomics to distinguish the signature of purifying selection. Computationally identified features can then be efficiently targeted for experimental analysis. Here we analyze alignments of protein-coding virus sequences to identify regions where there is a statistically significant reduction in the degree of variability at synonymous sites, a characteristic signature of overlapping functional elements. Having previously tested this technique by experimental verification of discoveries in selected viruses, we now analyze sequence alignments for ∼700 RNA virus species to identify hundreds of such regions, many of which have not been previously described.",2014 Nov 10,"Firth, Andrew E.",Nucleic Acids Res,,,True
7dfaa4c09d874ca072da1848411baba5c552b8f9,PMC,G-quadruplexes in viruses: function and potential therapeutic applications,http://dx.doi.org/10.1093/nar/gku999,PMC4227801,25332402,CC BY,"G-rich nucleic acids can form non-canonical G-quadruplex structures (G4s) in which four guanines fold in a planar arrangement through Hoogsteen hydrogen bonds. Although many biochemical and structural studies have focused on DNA sequences containing successive, adjacent guanines that spontaneously fold into G4s, evidence for their in vivo relevance has recently begun to accumulate. Complete sequencing of the human genome highlighted the presence of ∼300 000 sequences that can potentially form G4s. Likewise, the presence of putative G4-sequences has been reported in various viruses genomes [e.g., Human immunodeficiency virus (HIV-1), Epstein–Barr virus (EBV), papillomavirus (HPV)]. Many studies have focused on telomeric G4s and how their dynamics are regulated to enable telomere synthesis. Moreover, a role for G4s has been proposed in cellular and viral replication, recombination and gene expression control. In parallel, DNA aptamers that form G4s have been described as inhibitors and diagnostic tools to detect viruses [e.g., hepatitis A virus (HAV), EBV, cauliflower mosaic virus (CaMV), severe acute respiratory syndrome virus (SARS), simian virus 40 (SV40)]. Here, special emphasis will be given to the possible role of these structures in a virus life cycle as well as the use of G4-forming oligonucleotides as potential antiviral agents and innovative tools.",2014 Nov 10,"['Métifiot, Mathieu', 'Amrane, Samir', 'Litvak, Simon', 'Andreola, Marie-Line']",Nucleic Acids Res,,,True
c992817218f27eaa39a7bc3b90e9bd0538017eb0,PMC,Applying evolutionary concepts to wildlife disease ecology and management,http://dx.doi.org/10.1111/eva.12168,PMC4227862,25469163,CC BY,"Existing and emerging infectious diseases are among the most pressing global threats to biodiversity, food safety and human health. The complex interplay between host, pathogen and environment creates a challenge for conserving species, communities and ecosystem functions, while mediating the many known ecological and socio-economic negative effects of disease. Despite the clear ecological and evolutionary contexts of host–pathogen dynamics, approaches to managing wildlife disease remain predominantly reactionary, focusing on surveillance and some attempts at eradication. A few exceptional studies have heeded recent calls for better integration of ecological concepts in the study and management of wildlife disease; however, evolutionary concepts remain underused. Applied evolution consists of four principles: evolutionary history, genetic and phenotypic variation, selection and eco-evolutionary dynamics. In this article, we first update a classical framework for understanding wildlife disease to integrate better these principles. Within this framework, we explore the evolutionary implications of environment–disease interactions. Subsequently, we synthesize areas where applied evolution can be employed in wildlife disease management. Finally, we discuss some future directions and challenges. Here, we underscore that despite some evolutionary principles currently playing an important role in our understanding of disease in wild animals, considerable opportunities remain for fostering the practice of evolutionarily enlightened wildlife disease management.",2014 Aug 31,"['Vander Wal, Eric', 'Garant, Dany', 'Calmé, Sophie', 'Chapman, Colin A', 'Festa-Bianchet, Marco', 'Millien, Virginie', 'Rioux-Paquette, Sébastien', 'Pelletier, Fanie']",Evol Appl,,,True
7f8fc0ff30e4455d834e829db27b8d529b2920df,PMC,Automated analysis of phylogenetic clusters,http://dx.doi.org/10.1186/1471-2105-14-317,PMC4228337,24191891,CC BY,"BACKGROUND: As sequence data sets used for the investigation of pathogen transmission patterns increase in size, automated tools and standardized methods for cluster analysis have become necessary. We have developed an automated Cluster Picker which identifies monophyletic clades meeting user-input criteria for bootstrap support and maximum genetic distance within large phylogenetic trees. A second tool, the Cluster Matcher, automates the process of linking genetic data to epidemiological or clinical data, and matches clusters between runs of the Cluster Picker. RESULTS: We explore the effect of different bootstrap and genetic distance thresholds on clusters identified in a data set of publicly available HIV sequences, and compare these results to those of a previously published tool for cluster identification. To demonstrate their utility, we then use the Cluster Picker and Cluster Matcher together to investigate how clusters in the data set changed over time. We find that clusters containing sequences from more than one UK location at the first time point (multiple origin) were significantly more likely to grow than those representing only a single location. CONCLUSIONS: The Cluster Picker and Cluster Matcher can rapidly process phylogenetic trees containing tens of thousands of sequences. Together these tools will facilitate comparisons of pathogen transmission dynamics between studies and countries.",2013 Nov 6,"['Ragonnet-Cronin, Manon', 'Hodcroft, Emma', 'Hué, Stéphane', 'Fearnhill, Esther', 'Delpech, Valerie', 'Brown, Andrew J Leigh', 'Lycett, Samantha']",BMC Bioinformatics,,,True
62a1f5bb2940b4c4c29338c8f9fc47fd431aed28,PMC,Automated analysis of phylogenetic clusters,http://dx.doi.org/10.1186/1471-2105-14-317,PMC4228337,24191891,CC BY,"BACKGROUND: As sequence data sets used for the investigation of pathogen transmission patterns increase in size, automated tools and standardized methods for cluster analysis have become necessary. We have developed an automated Cluster Picker which identifies monophyletic clades meeting user-input criteria for bootstrap support and maximum genetic distance within large phylogenetic trees. A second tool, the Cluster Matcher, automates the process of linking genetic data to epidemiological or clinical data, and matches clusters between runs of the Cluster Picker. RESULTS: We explore the effect of different bootstrap and genetic distance thresholds on clusters identified in a data set of publicly available HIV sequences, and compare these results to those of a previously published tool for cluster identification. To demonstrate their utility, we then use the Cluster Picker and Cluster Matcher together to investigate how clusters in the data set changed over time. We find that clusters containing sequences from more than one UK location at the first time point (multiple origin) were significantly more likely to grow than those representing only a single location. CONCLUSIONS: The Cluster Picker and Cluster Matcher can rapidly process phylogenetic trees containing tens of thousands of sequences. Together these tools will facilitate comparisons of pathogen transmission dynamics between studies and countries.",2013 Nov 6,"['Ragonnet-Cronin, Manon', 'Hodcroft, Emma', 'Hué, Stéphane', 'Fearnhill, Esther', 'Delpech, Valerie', 'Brown, Andrew J Leigh', 'Lycett, Samantha']",BMC Bioinformatics,,,True
0c59c6dbfbf29fb7f0872efe3204551c75f79d02,PMC,Automated analysis of phylogenetic clusters,http://dx.doi.org/10.1186/1471-2105-14-317,PMC4228337,24191891,CC BY,"BACKGROUND: As sequence data sets used for the investigation of pathogen transmission patterns increase in size, automated tools and standardized methods for cluster analysis have become necessary. We have developed an automated Cluster Picker which identifies monophyletic clades meeting user-input criteria for bootstrap support and maximum genetic distance within large phylogenetic trees. A second tool, the Cluster Matcher, automates the process of linking genetic data to epidemiological or clinical data, and matches clusters between runs of the Cluster Picker. RESULTS: We explore the effect of different bootstrap and genetic distance thresholds on clusters identified in a data set of publicly available HIV sequences, and compare these results to those of a previously published tool for cluster identification. To demonstrate their utility, we then use the Cluster Picker and Cluster Matcher together to investigate how clusters in the data set changed over time. We find that clusters containing sequences from more than one UK location at the first time point (multiple origin) were significantly more likely to grow than those representing only a single location. CONCLUSIONS: The Cluster Picker and Cluster Matcher can rapidly process phylogenetic trees containing tens of thousands of sequences. Together these tools will facilitate comparisons of pathogen transmission dynamics between studies and countries.",2013 Nov 6,"['Ragonnet-Cronin, Manon', 'Hodcroft, Emma', 'Hué, Stéphane', 'Fearnhill, Esther', 'Delpech, Valerie', 'Brown, Andrew J Leigh', 'Lycett, Samantha']",BMC Bioinformatics,,,False
f47e681d9221b89b8872886fc50a7ec0f411f799,PMC,Automated analysis of phylogenetic clusters,http://dx.doi.org/10.1186/1471-2105-14-317,PMC4228337,24191891,CC BY,"BACKGROUND: As sequence data sets used for the investigation of pathogen transmission patterns increase in size, automated tools and standardized methods for cluster analysis have become necessary. We have developed an automated Cluster Picker which identifies monophyletic clades meeting user-input criteria for bootstrap support and maximum genetic distance within large phylogenetic trees. A second tool, the Cluster Matcher, automates the process of linking genetic data to epidemiological or clinical data, and matches clusters between runs of the Cluster Picker. RESULTS: We explore the effect of different bootstrap and genetic distance thresholds on clusters identified in a data set of publicly available HIV sequences, and compare these results to those of a previously published tool for cluster identification. To demonstrate their utility, we then use the Cluster Picker and Cluster Matcher together to investigate how clusters in the data set changed over time. We find that clusters containing sequences from more than one UK location at the first time point (multiple origin) were significantly more likely to grow than those representing only a single location. CONCLUSIONS: The Cluster Picker and Cluster Matcher can rapidly process phylogenetic trees containing tens of thousands of sequences. Together these tools will facilitate comparisons of pathogen transmission dynamics between studies and countries.",2013 Nov 6,"['Ragonnet-Cronin, Manon', 'Hodcroft, Emma', 'Hué, Stéphane', 'Fearnhill, Esther', 'Delpech, Valerie', 'Brown, Andrew J Leigh', 'Lycett, Samantha']",BMC Bioinformatics,,,False
84323c90f9a4e2e339105377d6a0769cc2fa0fbc,PMC,Activation of Innate Immune-Response Genes in Little Brown Bats (Myotis lucifugus) Infected with the Fungus Pseudogymnoascus destructans,http://dx.doi.org/10.1371/journal.pone.0112285,PMC4229191,25391018,CC BY,"Recently bats have been associated with the emergence of diseases, both as reservoirs for several new viral diseases in humans and other animals and, in the northern Americas, as hosts for a devastating fungal disease that threatens to drive several bat species to regional extinction. However, despite these catastrophic events little Information is available on bat defences or how they interact with their pathogens. Even less is known about the response of bats to infection during torpor or long-term hibernation. Using tissue samples collected at the termination of an experiment to explore the pathogenesis of White Nose Syndrome in Little Brown Bats, we determined if hibernating bats infected with the fungus Pseudogymnoascus destructans could respond to infection by activating genes responsible for innate immune and stress responses. Lesions due to fungal infection and, in some cases, secondary bacterial infections, were restricted to the skin. However, we were unable to obtain sufficient amounts of RNA from these sites. We therefore examined lungs for response at an epithelial surface not linked to the primary site of infection. We found that bats responded to infection with a significant increase in lungs of transcripts for Cathelicidin (an anti-microbial peptide) as well as the immune modulators tumor necrosis factor alpha and interleukins 10 and 23. In conclusion, hibernating bats can respond to experimental P. destructans infection by activating expression of innate immune response genes.",2014 Nov 12,"['Rapin, Noreen', 'Johns, Kirk', 'Martin, Lauren', 'Warnecke, Lisa', 'Turner, James M.', 'Bollinger, Trent K.', 'Willis, Craig K. R.', 'Voyles, Jamie', 'Misra, Vikram']",PLoS One,,,True
77f34000cd69ab822903562a0004012eeebe7605,PMC,Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury,http://dx.doi.org/10.1038/srep07027,PMC4229671,25391767,CC BY,"Since March 2013, the emergence of an avian-origin influenza A (H7N9) virus has raised concern in China. Although most infections resulted in respiratory illness, some severe cases resulted in acute respiratory distress syndrome (ARDS), which is a severe form of acute lung injury (ALI) that further contributes to morbidity. To date, no effective drugs that improve the clinical outcome of influenza A (H7N9) virus-infected patients have been identified. Angiotensin-converting enzyme (ACE) and ACE2 are involved in several pathologies such as cardiovascular functions, renal disease, and acute lung injury. In the current study, we report that ACE2 could mediate the severe acute lung injury induced by influenza A (H7N9) virus infection in an experimental mouse model. Moreover, ACE2 deficiency worsened the disease pathogenesis markedly, mainly by targeting the angiotensin II type 1 receptor (AT1). The current findings demonstrate that ACE2 plays a critical role in influenza A (H7N9) virus-induced acute lung injury, and suggest that might be a useful potential therapeutic target for future influenza A (H7N9) outbreaks.",2014 Nov 13,"['Yang, Penghui', 'Gu, Hongjing', 'Zhao, Zhongpeng', 'Wang, Wei', 'Cao, Bin', 'Lai, Chengcai', 'Yang, Xiaolan', 'Zhang, LiangYan', 'Duan, Yueqiang', 'Zhang, Shaogeng', 'Chen, Weiwen', 'Zhen, Wenbo', 'Cai, Maosheng', 'Penninger, Josef M.', 'Jiang, Chengyu', 'Wang, Xiliang']",Sci Rep,,,True
ba3471e86d6880f42f1df67c9a381e83216d1b45,PMC,From sequence to enzyme mechanism using multi-label machine learning,http://dx.doi.org/10.1186/1471-2105-15-150,PMC4229970,24885296,CC BY,"BACKGROUND: In this work we predict enzyme function at the level of chemical mechanism, providing a finer granularity of annotation than traditional Enzyme Commission (EC) classes. Hence we can predict not only whether a putative enzyme in a newly sequenced organism has the potential to perform a certain reaction, but how the reaction is performed, using which cofactors and with susceptibility to which drugs or inhibitors, details with important consequences for drug and enzyme design. Work that predicts enzyme catalytic activity based on 3D protein structure features limits the prediction of mechanism to proteins already having either a solved structure or a close relative suitable for homology modelling. RESULTS: In this study, we evaluate whether sequence identity, InterPro or Catalytic Site Atlas sequence signatures provide enough information for bulk prediction of enzyme mechanism. By splitting MACiE (Mechanism, Annotation and Classification in Enzymes database) mechanism labels to a finer granularity, which includes the role of the protein chain in the overall enzyme complex, the method can predict at 96% accuracy (and 96% micro-averaged precision, 99.9% macro-averaged recall) the MACiE mechanism definitions of 248 proteins available in the MACiE, EzCatDb (Database of Enzyme Catalytic Mechanisms) and SFLD (Structure Function Linkage Database) databases using an off-the-shelf K-Nearest Neighbours multi-label algorithm. CONCLUSION: We find that InterPro signatures are critical for accurate prediction of enzyme mechanism. We also find that incorporating Catalytic Site Atlas attributes does not seem to provide additional accuracy. The software code (ml2db), data and results are available online at http://sourceforge.net/projects/ml2db/ and as supplementary files.",2014 May 19,"['De Ferrari, Luna', 'Mitchell, John BO']",BMC Bioinformatics,,,True
29688d13b2e9b0f1ce17caa2ec6591c9792f50ba,PMC,From sequence to enzyme mechanism using multi-label machine learning,http://dx.doi.org/10.1186/1471-2105-15-150,PMC4229970,24885296,CC BY,"BACKGROUND: In this work we predict enzyme function at the level of chemical mechanism, providing a finer granularity of annotation than traditional Enzyme Commission (EC) classes. Hence we can predict not only whether a putative enzyme in a newly sequenced organism has the potential to perform a certain reaction, but how the reaction is performed, using which cofactors and with susceptibility to which drugs or inhibitors, details with important consequences for drug and enzyme design. Work that predicts enzyme catalytic activity based on 3D protein structure features limits the prediction of mechanism to proteins already having either a solved structure or a close relative suitable for homology modelling. RESULTS: In this study, we evaluate whether sequence identity, InterPro or Catalytic Site Atlas sequence signatures provide enough information for bulk prediction of enzyme mechanism. By splitting MACiE (Mechanism, Annotation and Classification in Enzymes database) mechanism labels to a finer granularity, which includes the role of the protein chain in the overall enzyme complex, the method can predict at 96% accuracy (and 96% micro-averaged precision, 99.9% macro-averaged recall) the MACiE mechanism definitions of 248 proteins available in the MACiE, EzCatDb (Database of Enzyme Catalytic Mechanisms) and SFLD (Structure Function Linkage Database) databases using an off-the-shelf K-Nearest Neighbours multi-label algorithm. CONCLUSION: We find that InterPro signatures are critical for accurate prediction of enzyme mechanism. We also find that incorporating Catalytic Site Atlas attributes does not seem to provide additional accuracy. The software code (ml2db), data and results are available online at http://sourceforge.net/projects/ml2db/ and as supplementary files.",2014 May 19,"['De Ferrari, Luna', 'Mitchell, John BO']",BMC Bioinformatics,,,False
c181d32e2efda26882425f6179dc5549a59a3504,PMC,ADLD: A Novel Graphical Representation of Protein Sequences and Its Application,http://dx.doi.org/10.1155/2014/959753,PMC4230005,25530796,CC BY,"To facilitate the intuitional analysis of protein sequences, a novel graphical representation of protein sequences called ADLD (Alignment Diagonal Line Diagram) is introduced in this paper first, and then a new ADLD based method is proposed and utilized to analyze the similarity/dissimilarity of protein sequences. Comparing with existing methods, our ADLD based method is proved to be effective in the similarity/dissimilarity analysis of protein sequences and have the merits of good intuition, visuality, and simplicity. The examinations of the similarities/dissimilarities for both the 16 different ND5 proteins and the 29 different spike proteins illustrate the utility of our ADLD based approach.",2014 Oct 30,"['Wang, Lei', 'Peng, Hui', 'Zheng, Jinhua']",Comput Math Methods Med,,,True
dc4a3df470bfd502db850deec4219e39f7eadb63,PMC,Immune Responses to Non-Tumor Antigens in the Central Nervous System,http://dx.doi.org/10.3389/fonc.2014.00328,PMC4230036,25431758,CC BY,"The central nervous system (CNS), once viewed as an immune-privileged site protected by the blood–brain barrier (BBB), is now known to be a dynamic immunological environment through which immune cells migrate to prevent and respond to events such as localized infection. During these responses, endogenous glial cells, including astrocytes and microglia, become highly reactive and may secrete inflammatory mediators that regulate BBB permeability and recruit additional circulating immune cells. Here, we discuss the various roles played by astrocytes, microglia, and infiltrating immune cells during host immunity to non-tumor antigens in the CNS, focusing first on bacterial and viral infections, and then turning to responses directed against self-antigens in the setting of CNS autoimmunity.",2014 Nov 13,"['Huber, Amanda K.', 'Duncker, Patrick C.', 'Irani, David N.']",Front Oncol,,,True
58246d246bb1b2288dc58245c475fc314d34cc83,PMC,Role of Oct4 in the early embryo development,http://dx.doi.org/10.1186/2045-9769-3-7,PMC4230828,25408886,CC BY,"Oct4 is a key component of the pluripotency regulatory network, and its reciprocal interaction with Cdx2 has been shown to be a determinant of either the self-renewal of embryonic stem cells (ESCs) or their differentiation into trophoblast. Oct4 of maternal origin is postulated to play critical role in defining totipotency and inducing pluripotency during embryonic development. However, the genetic elimination of maternal Oct4 using a Cre-lox approach in mouse revealed that the establishment of totipotency in maternal Oct4–depleted embryos was not affected, and that these embryos could complete full-term development without any obvious defect. These results indicate that Oct4 is not essential for the initiation of pluripotency, in contrast to its critical role in maintaining pluripotency. This conclusion is further supported by the formation of Oct4-GFP– and Nanog- expressing inner cell masses (ICMs) in embryos with complete inactivation of both maternal and zygotic Oct4 expression and the reprogramming of fibroblasts into fully pluripotent cells by Oct4-deficient oocytes.",2014 Apr 29,"['Wu, Guangming', 'Schöler, Hans R']",Cell Regen (Lond),,,True
5b7e79c51c0788a3bb6e9c3a67e37d2dfedf9541,PMC,"The Global One Health Paradigm: Challenges and Opportunities for Tackling Infectious Diseases at the Human, Animal, and Environment Interface in Low-Resource Settings",http://dx.doi.org/10.1371/journal.pntd.0003257,PMC4230840,25393303,CC BY,"Zoonotic infectious diseases have been an important concern to humankind for more than 10,000 years. Today, approximately 75% of newly emerging infectious diseases (EIDs) are zoonoses that result from various anthropogenic, genetic, ecologic, socioeconomic, and climatic factors. These interrelated driving forces make it difficult to predict and to prevent zoonotic EIDs. Although significant improvements in environmental and medical surveillance, clinical diagnostic methods, and medical practices have been achieved in the recent years, zoonotic EIDs remain a major global concern, and such threats are expanding, especially in less developed regions. The current Ebola epidemic in West Africa is an extreme stark reminder of the role animal reservoirs play in public health and reinforces the urgent need for globally operationalizing a One Health approach. The complex nature of zoonotic diseases and the limited resources in developing countries are a reminder that the need for implementation of Global One Health in low-resource settings is crucial. The Veterinary Public Health and Biotechnology (VPH-Biotec) Global Consortium launched the International Congress on Pathogens at the Human-Animal Interface (ICOPHAI) in order to address important challenges and needs for capacity building. The inaugural ICOPHAI (Addis Ababa, Ethiopia, 2011) and the second congress (Porto de Galinhas, Brazil, 2013) were unique opportunities to share and discuss issues related to zoonotic infectious diseases worldwide. In addition to strong scientific reports in eight thematic areas that necessitate One Health implementation, the congress identified four key capacity-building needs: (1) development of adequate science-based risk management policies, (2) skilled-personnel capacity building, (3) accredited veterinary and public health diagnostic laboratories with a shared database, and (4) improved use of existing natural resources and implementation. The aim of this review is to highlight advances in key zoonotic disease areas and the One Health capacity needs.",2014 Nov 13,"['Gebreyes, Wondwossen A.', 'Dupouy-Camet, Jean', 'Newport, Melanie J.', 'Oliveira, Celso J. B.', 'Schlesinger, Larry S.', 'Saif, Yehia M.', 'Kariuki, Samuel', 'Saif, Linda J.', 'Saville, William', 'Wittum, Thomas', 'Hoet, Armando', 'Quessy, Sylvain', 'Kazwala, Rudovick', 'Tekola, Berhe', 'Shryock, Thomas', 'Bisesi, Michael', 'Patchanee, Prapas', 'Boonmar, Sumalee', 'King, Lonnie J.']",PLoS Negl Trop Dis,,,True
b3d980d9df2556687fc5d6bf3b18c95215da600c,PMC,Atomistic Detailed Mechanism and Weak Cation-Conducting Activity of HIV-1 Vpu Revealed by Free Energy Calculations,http://dx.doi.org/10.1371/journal.pone.0112983,PMC4231112,25392993,CC BY,"The viral protein U (Vpu) encoded by HIV-1 has been shown to assist in the detachment of virion particles from infected cells. Vpu forms cation-specific ion channels in host cells, and has been proposed as a potential drug target. An understanding of the mechanism of ion transport through Vpu is desirable, but remains limited because of the unavailability of an experimental structure of the channel. Using a structure of the pentameric form of Vpu – modeled and validated based on available experimental data – umbrella sampling molecular dynamics simulations (cumulative simulation time of more than 0.4 µs) were employed to elucidate the energetics and the molecular mechanism of ion transport in Vpu. Free energy profiles corresponding to the permeation of Na(+) and K(+) were found to be similar to each other indicating lack of ion selection, consistent with previous experimental studies. The Ser23 residue is shown to enhance ion transport via two mechanisms: creating a weak binding site, and increasing the effective hydrophilic length of the channel, both of which have previously been hypothesized in experiments. A two-dimensional free energy landscape has been computed to model multiple ion permeation, based on which a mechanism for ion conduction is proposed. It is shown that only one ion can pass through the channel at a time. This, along with a stretch of hydrophobic residues in the transmembrane domain of Vpu, explains the slow kinetics of ion conduction. The results are consistent with previous conductance studies that showed Vpu to be a weakly conducting ion channel.",2014 Nov 13,"['Padhi, Siladitya', 'Burri, Raghunadha Reddy', 'Jameel, Shahid', 'Priyakumar, U. Deva']",PLoS One,,,True
991fb0c5b5cd686d096e2b05d8dc19ca22213df4,PMC,Induction of robust immunity response in mice by dual-expression-system-based recombinant baculovirus expressing the capsid protein of porcine circovirus type 2,http://dx.doi.org/10.1186/1743-422X-10-316,PMC4231451,24161107,CC BY,"BACKGROUND: Porcine circovirus type 2 (PCV2) is associated with post-weaning multisystemic wasting syndrome (PMWS), an emerging swine disease that causes progressive weight loss, dyspnea, tachypnea, anemia, jaundice, and diarrhea in piglets. Although baculovirus is an enveloped virus that infects insects in nature, it has emerged as a vaccine vector, and we used it to develop a novel candidate vaccine for a preventive or therapeutic strategy to control PCV2 infections. METHODS: Immunoblotting analysis of recombinant baculovirus and immunofluorescent staining of baculovirus-infected cells were followed using anti-ORF2 monoclonal antibodies. The BALB/c mice were immunized intramuscularly with this baculovirus. The titers of antibodies were mensurated with a Cap-protein-specific enzyme-linked immunosorbent assay (ELISA) and a serum neutralization assay. The IFN-γ response in splenocytes harvested from immunized mice was measured by ELISA. Student's t-test was used to compare immune responses of different groups. RESULTS: In this study, we successfully constructed a dual-expression-system-based recombinant baculovirus BV-GD-ORF2, which can display the PCV2 capsid (Cap) protein and VSV-G protein on the viral envelope and also expressing Cap protein on transduced mammalian cells, thereby functioning as both a subunit and a DNA vaccine. After infection, the Cap protein was expressed and displayed on the viral surface, as demonstrated with an indirect fluorescence assay and immunoblotting. The vaccination of mice with recombinant baculovirus BV-GD-ORF2 successfully induced robust Cap-protein-specific humoral and cellular immune responses. CONCLUSIONS: Our findings collectively demonstrate that the recombinant baculovirus BV-GD-ORF2 is a potential vaccine against PCV2 infections.",2013 Oct 28,"['Ye, Yu', 'Cheng, Xiaoliang', 'Zhang, Jie', 'Tong, Tiezhu', 'Lin, Wenyao', 'Liao, Ming', 'Fan, Huiying']",Virol J,,,True
f11b19a9e1845ff5ab66a42d5409f8caed24faa1,PMC,"Sequencing, Annotation and Analysis of the Syrian Hamster (Mesocricetus auratus) Transcriptome",http://dx.doi.org/10.1371/journal.pone.0112617,PMC4232415,25398096,CC0,"BACKGROUND: The Syrian hamster (golden hamster, Mesocricetus auratus) is gaining importance as a new experimental animal model for multiple pathogens, including emerging zoonotic diseases such as Ebola. Nevertheless there are currently no publicly available transcriptome reference sequences or genome for this species. RESULTS: A cDNA library derived from mRNA and snRNA isolated and pooled from the brains, lungs, spleens, kidneys, livers, and hearts of three adult female Syrian hamsters was sequenced. Sequence reads were assembled into 62,482 contigs and 111,796 reads remained unassembled (singletons). This combined contig/singleton dataset, designated as the Syrian hamster transcriptome, represents a total of 60,117,204 nucleotides. Our Mesocricetus auratus Syrian hamster transcriptome mapped to 11,648 mouse transcripts representing 9,562 distinct genes, and mapped to a similar number of transcripts and genes in the rat. We identified 214 quasi-complete transcripts based on mouse annotations. Canonical pathways involved in a broad spectrum of fundamental biological processes were significantly represented in the library. The Syrian hamster transcriptome was aligned to the current release of the Chinese hamster ovary (CHO) cell transcriptome and genome to improve the genomic annotation of this species. Finally, our Syrian hamster transcriptome was aligned against 14 other rodents, primate and laurasiatheria species to gain insights about the genetic relatedness and placement of this species. CONCLUSIONS: This Syrian hamster transcriptome dataset significantly improves our knowledge of the Syrian hamster's transcriptome, especially towards its future use in infectious disease research. Moreover, this library is an important resource for the wider scientific community to help improve genome annotation of the Syrian hamster and other closely related species. Furthermore, these data provide the basis for development of expression microarrays that can be used in functional genomics studies.",2014 Nov 14,"['Tchitchek, Nicolas', 'Safronetz, David', 'Rasmussen, Angela L.', 'Martens, Craig', 'Virtaneva, Kimmo', 'Porcella, Stephen F.', 'Feldmann, Heinz', 'Ebihara, Hideki', 'Katze, Michael G.']",PLoS One,,,True
1248f79908add5049ea87ca9c44b851d841d5b54,PMC,"Sequencing, Annotation and Analysis of the Syrian Hamster (Mesocricetus auratus) Transcriptome",http://dx.doi.org/10.1371/journal.pone.0112617,PMC4232415,25398096,CC0,"BACKGROUND: The Syrian hamster (golden hamster, Mesocricetus auratus) is gaining importance as a new experimental animal model for multiple pathogens, including emerging zoonotic diseases such as Ebola. Nevertheless there are currently no publicly available transcriptome reference sequences or genome for this species. RESULTS: A cDNA library derived from mRNA and snRNA isolated and pooled from the brains, lungs, spleens, kidneys, livers, and hearts of three adult female Syrian hamsters was sequenced. Sequence reads were assembled into 62,482 contigs and 111,796 reads remained unassembled (singletons). This combined contig/singleton dataset, designated as the Syrian hamster transcriptome, represents a total of 60,117,204 nucleotides. Our Mesocricetus auratus Syrian hamster transcriptome mapped to 11,648 mouse transcripts representing 9,562 distinct genes, and mapped to a similar number of transcripts and genes in the rat. We identified 214 quasi-complete transcripts based on mouse annotations. Canonical pathways involved in a broad spectrum of fundamental biological processes were significantly represented in the library. The Syrian hamster transcriptome was aligned to the current release of the Chinese hamster ovary (CHO) cell transcriptome and genome to improve the genomic annotation of this species. Finally, our Syrian hamster transcriptome was aligned against 14 other rodents, primate and laurasiatheria species to gain insights about the genetic relatedness and placement of this species. CONCLUSIONS: This Syrian hamster transcriptome dataset significantly improves our knowledge of the Syrian hamster's transcriptome, especially towards its future use in infectious disease research. Moreover, this library is an important resource for the wider scientific community to help improve genome annotation of the Syrian hamster and other closely related species. Furthermore, these data provide the basis for development of expression microarrays that can be used in functional genomics studies.",2014 Nov 14,"['Tchitchek, Nicolas', 'Safronetz, David', 'Rasmussen, Angela L.', 'Martens, Craig', 'Virtaneva, Kimmo', 'Porcella, Stephen F.', 'Feldmann, Heinz', 'Ebihara, Hideki', 'Katze, Michael G.']",PLoS One,,,False
cc653d610df635aab4288b596359b83a38eb123b,PMC,"Sequencing, Annotation and Analysis of the Syrian Hamster (Mesocricetus auratus) Transcriptome",http://dx.doi.org/10.1371/journal.pone.0112617,PMC4232415,25398096,CC0,"BACKGROUND: The Syrian hamster (golden hamster, Mesocricetus auratus) is gaining importance as a new experimental animal model for multiple pathogens, including emerging zoonotic diseases such as Ebola. Nevertheless there are currently no publicly available transcriptome reference sequences or genome for this species. RESULTS: A cDNA library derived from mRNA and snRNA isolated and pooled from the brains, lungs, spleens, kidneys, livers, and hearts of three adult female Syrian hamsters was sequenced. Sequence reads were assembled into 62,482 contigs and 111,796 reads remained unassembled (singletons). This combined contig/singleton dataset, designated as the Syrian hamster transcriptome, represents a total of 60,117,204 nucleotides. Our Mesocricetus auratus Syrian hamster transcriptome mapped to 11,648 mouse transcripts representing 9,562 distinct genes, and mapped to a similar number of transcripts and genes in the rat. We identified 214 quasi-complete transcripts based on mouse annotations. Canonical pathways involved in a broad spectrum of fundamental biological processes were significantly represented in the library. The Syrian hamster transcriptome was aligned to the current release of the Chinese hamster ovary (CHO) cell transcriptome and genome to improve the genomic annotation of this species. Finally, our Syrian hamster transcriptome was aligned against 14 other rodents, primate and laurasiatheria species to gain insights about the genetic relatedness and placement of this species. CONCLUSIONS: This Syrian hamster transcriptome dataset significantly improves our knowledge of the Syrian hamster's transcriptome, especially towards its future use in infectious disease research. Moreover, this library is an important resource for the wider scientific community to help improve genome annotation of the Syrian hamster and other closely related species. Furthermore, these data provide the basis for development of expression microarrays that can be used in functional genomics studies.",2014 Nov 14,"['Tchitchek, Nicolas', 'Safronetz, David', 'Rasmussen, Angela L.', 'Martens, Craig', 'Virtaneva, Kimmo', 'Porcella, Stephen F.', 'Feldmann, Heinz', 'Ebihara, Hideki', 'Katze, Michael G.']",PLoS One,,,False
9650f6d8d76fe3f5624405c98b967b6b6a424e01,PMC,"Sequencing, Annotation and Analysis of the Syrian Hamster (Mesocricetus auratus) Transcriptome",http://dx.doi.org/10.1371/journal.pone.0112617,PMC4232415,25398096,CC0,"BACKGROUND: The Syrian hamster (golden hamster, Mesocricetus auratus) is gaining importance as a new experimental animal model for multiple pathogens, including emerging zoonotic diseases such as Ebola. Nevertheless there are currently no publicly available transcriptome reference sequences or genome for this species. RESULTS: A cDNA library derived from mRNA and snRNA isolated and pooled from the brains, lungs, spleens, kidneys, livers, and hearts of three adult female Syrian hamsters was sequenced. Sequence reads were assembled into 62,482 contigs and 111,796 reads remained unassembled (singletons). This combined contig/singleton dataset, designated as the Syrian hamster transcriptome, represents a total of 60,117,204 nucleotides. Our Mesocricetus auratus Syrian hamster transcriptome mapped to 11,648 mouse transcripts representing 9,562 distinct genes, and mapped to a similar number of transcripts and genes in the rat. We identified 214 quasi-complete transcripts based on mouse annotations. Canonical pathways involved in a broad spectrum of fundamental biological processes were significantly represented in the library. The Syrian hamster transcriptome was aligned to the current release of the Chinese hamster ovary (CHO) cell transcriptome and genome to improve the genomic annotation of this species. Finally, our Syrian hamster transcriptome was aligned against 14 other rodents, primate and laurasiatheria species to gain insights about the genetic relatedness and placement of this species. CONCLUSIONS: This Syrian hamster transcriptome dataset significantly improves our knowledge of the Syrian hamster's transcriptome, especially towards its future use in infectious disease research. Moreover, this library is an important resource for the wider scientific community to help improve genome annotation of the Syrian hamster and other closely related species. Furthermore, these data provide the basis for development of expression microarrays that can be used in functional genomics studies.",2014 Nov 14,"['Tchitchek, Nicolas', 'Safronetz, David', 'Rasmussen, Angela L.', 'Martens, Craig', 'Virtaneva, Kimmo', 'Porcella, Stephen F.', 'Feldmann, Heinz', 'Ebihara, Hideki', 'Katze, Michael G.']",PLoS One,,,False
21b5f4d12c8a8f488141e25fd334b4cc6e6270d2,PMC,"Sequencing, Annotation and Analysis of the Syrian Hamster (Mesocricetus auratus) Transcriptome",http://dx.doi.org/10.1371/journal.pone.0112617,PMC4232415,25398096,CC0,"BACKGROUND: The Syrian hamster (golden hamster, Mesocricetus auratus) is gaining importance as a new experimental animal model for multiple pathogens, including emerging zoonotic diseases such as Ebola. Nevertheless there are currently no publicly available transcriptome reference sequences or genome for this species. RESULTS: A cDNA library derived from mRNA and snRNA isolated and pooled from the brains, lungs, spleens, kidneys, livers, and hearts of three adult female Syrian hamsters was sequenced. Sequence reads were assembled into 62,482 contigs and 111,796 reads remained unassembled (singletons). This combined contig/singleton dataset, designated as the Syrian hamster transcriptome, represents a total of 60,117,204 nucleotides. Our Mesocricetus auratus Syrian hamster transcriptome mapped to 11,648 mouse transcripts representing 9,562 distinct genes, and mapped to a similar number of transcripts and genes in the rat. We identified 214 quasi-complete transcripts based on mouse annotations. Canonical pathways involved in a broad spectrum of fundamental biological processes were significantly represented in the library. The Syrian hamster transcriptome was aligned to the current release of the Chinese hamster ovary (CHO) cell transcriptome and genome to improve the genomic annotation of this species. Finally, our Syrian hamster transcriptome was aligned against 14 other rodents, primate and laurasiatheria species to gain insights about the genetic relatedness and placement of this species. CONCLUSIONS: This Syrian hamster transcriptome dataset significantly improves our knowledge of the Syrian hamster's transcriptome, especially towards its future use in infectious disease research. Moreover, this library is an important resource for the wider scientific community to help improve genome annotation of the Syrian hamster and other closely related species. Furthermore, these data provide the basis for development of expression microarrays that can be used in functional genomics studies.",2014 Nov 14,"['Tchitchek, Nicolas', 'Safronetz, David', 'Rasmussen, Angela L.', 'Martens, Craig', 'Virtaneva, Kimmo', 'Porcella, Stephen F.', 'Feldmann, Heinz', 'Ebihara, Hideki', 'Katze, Michael G.']",PLoS One,,,False
4ed270652370f2ffd9aecd7288519c77d7b925ea,PMC,Hijacking of an autophagy-like process is critical for the life cycle of a DNA virus infecting oceanic algal blooms,http://dx.doi.org/10.1111/nph.13008,PMC4233938,25195618,CC BY,"Marine photosynthetic microorganisms are the basis of marine food webs and are responsible for nearly 50% of the global primary production. Emiliania huxleyi forms massive oceanic blooms that are routinely terminated by large double-stranded DNA coccolithoviruses. The cellular mechanisms that govern the replication cycle of these giant viruses are largely unknown. We used diverse techniques, including fluorescence microscopy, transmission electron microscopy, cryoelectron tomography, immunolabeling and biochemical methodologies to investigate the role of autophagy in host–virus interactions. Hallmarks of autophagy are induced during the lytic phase of E. huxleyi viral infection, concomitant with up-regulation of autophagy-related genes (ATG genes). Pretreatment of the infected cells with an autophagy inhibitor causes a major reduction in the production of extracellular viral particles, without reducing viral DNA replication within the cell. The host-encoded Atg8 protein was detected within purified virions, demonstrating the pivotal role of the autophagy-like process in viral assembly and egress. We show that autophagy, which is classically considered as a defense mechanism, is essential for viral propagation and for facilitating a high burst size. This cellular mechanism may have a major impact on the fate of the viral-infected blooms, and therefore on the cycling of nutrients within the marine ecosystem.",2014 Dec 7,"['Schatz, Daniella', 'Shemi, Adva', 'Rosenwasser, Shilo', 'Sabanay, Helena', 'Wolf, Sharon G', 'Ben-Dor, Shifra', 'Vardi, Assaf']",New Phytol,,,True
7ac54db3298b52d9d78f4255e40447904bd90ad7,PMC,Enterovirus 71 Induces Mitochondrial Reactive Oxygen Species Generation That is Required for Efficient Replication,http://dx.doi.org/10.1371/journal.pone.0113234,PMC4234665,25401329,CC BY,"Redox homeostasis is an important host factor determining the outcome of infectious disease. Enterovirus 71 (EV71) infection has become an important endemic disease in Southeast Asia and China. We have previously shown that oxidative stress promotes viral replication, and progeny virus induces oxidative stress in host cells. The detailed mechanism for reactive oxygen species (ROS) generation in infected cells remains elusive. In the current study, we demonstrate that mitochondria were a major ROS source in EV71-infected cells. Mitochondria in productively infected cells underwent morphologic changes and exhibited functional anomalies, such as a decrease in mitochondrial electrochemical potential ΔΨ(m) and an increase in oligomycin-insensitive oxygen consumption. Respiratory control ratio of mitochondria from infected cells was significantly lower than that of normal cells. The total adenine nucleotide pool and ATP content of EV71-infected cells significantly diminished. However, there appeared to be a compensatory increase in mitochondrial mass. Treatment with mito-TEMPO reduced eIF2α phosphorylation and viral replication, suggesting that mitochondrial ROS act to promote viral replication. It is plausible that EV71 infection induces mitochondrial ROS generation, which is essential to viral replication, at the sacrifice of efficient energy production, and that infected cells up-regulate biogenesis of mitochondria to compensate for their functional defect.",2014 Nov 17,"['Cheng, Mei-Ling', 'Weng, Shiue-Fen', 'Kuo, Chih-Hao', 'Ho, Hung-Yao']",PLoS One,,,True
f04ae49e396269b6fc64538613ea9a6d53583bd6,PMC,Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley Fever vaccine in mice,http://dx.doi.org/10.1186/1743-422X-10-349,PMC4235025,24304565,CC BY,"BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. METHODS: Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. RESULTS: A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8(+) T cell response. CONCLUSIONS: Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.",2013 Dec 5,"['Warimwe, George M', 'Lorenzo, Gema', 'Lopez-Gil, Elena', 'Reyes-Sandoval, Arturo', 'Cottingham, Matthew G', 'Spencer, Alexandra J', 'Collins, Katharine A', 'Dicks, Matthew DJ', 'Milicic, Anita', 'Lall, Amar', 'Furze, Julie', 'Turner, Alison V', 'Hill, Adrian VS', 'Brun, Alejandro', 'Gilbert, Sarah C']",Virol J,,,True
ffd791c34aa1431d8571663c1fa722086d0ad90f,PMC,Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley Fever vaccine in mice,http://dx.doi.org/10.1186/1743-422X-10-349,PMC4235025,24304565,CC BY,"BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. METHODS: Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. RESULTS: A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8(+) T cell response. CONCLUSIONS: Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.",2013 Dec 5,"['Warimwe, George M', 'Lorenzo, Gema', 'Lopez-Gil, Elena', 'Reyes-Sandoval, Arturo', 'Cottingham, Matthew G', 'Spencer, Alexandra J', 'Collins, Katharine A', 'Dicks, Matthew DJ', 'Milicic, Anita', 'Lall, Amar', 'Furze, Julie', 'Turner, Alison V', 'Hill, Adrian VS', 'Brun, Alejandro', 'Gilbert, Sarah C']",Virol J,,,True
05e4c2f6b0affdeef1b7d99d5b481bee1c244a7f,PMC,Human Bocavirus: Lessons Learned to Date,http://dx.doi.org/10.3390/pathogens2010001,PMC4235705,25436878,CC BY,"Human bocavirus (HBoV) was identified as the second human parvovirus with pathogenic potential in 2005 in respiratory samples from children suffering from viral respiratory infections of unknown etiology. Since its first description, a large number of clinical studies have been performed that address the clinical significance of HBoV detection and the molecular biology of the virus. This review summarizes the most important steps taken in HBoV research to date and addresses open questions that need to be answered in the future to provide a better understanding of the role of a virus that is difficult to grow in cell culture and is suspected to be a pathogen, although it has not yet fulfilled Koch’s postulates.",2013 Jan 11,"Schildgen, Oliver",Pathogens,,,True
4be32977ea29039cf2fac3b4327ceea8f14d0af4,PMC,Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases,http://dx.doi.org/10.3390/pathogens2010153,PMC4235711,25436886,CC BY,"Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus.",2013 Mar 14,"['Fujiwara, Shigeyoshi', 'Matsuda, Go', 'Imadome, Ken-Ichi']",Pathogens,,,True
c9e24b269c1f1772454a1e93cc72c85251aeda6b,PMC,Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen,http://dx.doi.org/10.1371/journal.pone.0112602,PMC4236105,25405618,CC BY,"The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV) pandemic. Some studies have indicated the receptor-binding domain (RBD) protein of MERS-CoV spike (S) is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m.) with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum) alone, alum and polyriboinosinic acid (poly I:C) or alum and cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODN). The immune responses of mice vaccinated with RBD, incomplete Freund’s adjuvant (IFA) and CpG ODN by a subcutaneous (s.c.) route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies) and cellular immunity (ELISpot assay for IFN-γ spot-forming cells and splenocyte cytokine production). Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting effective humoral and cellular immune responses.",2014 Nov 18,"['Lan, Jiaming', 'Deng, Yao', 'Chen, Hong', 'Lu, Guangwen', 'Wang, Wen', 'Guo, Xiaojuan', 'Lu, Zhuozhuang', 'Gao, George F.', 'Tan, Wenjie']",PLoS One,,,True
085c71736d6b79717bb03aec375310d9e536f851,PMC,PTB Binds to the 3’ Untranslated Region of the Human Astrovirus Type 8: A Possible Role in Viral Replication,http://dx.doi.org/10.1371/journal.pone.0113113,PMC4236132,25406089,CC BY,"The 3′ untranslated region (3′UTR) of human astroviruses (HAstV) consists of two hairpin structures (helix I and II) joined by a linker harboring a conserved PTB/hnRNP1 binding site. The identification and characterization of cellular proteins that interact with the 3′UTR of HAstV-8 virus will help to uncover cellular requirements for viral functions. To this end, mobility shift assays and UV cross-linking were performed with uninfected and HAstV-8-infected cell extracts and HAstV-8 3′UTR probes. Two RNA-protein complexes (CI and CII) were recruited into the 3′UTR. Complex CII formation was compromised with cold homologous RNA, and seven proteins of 35, 40, 45, 50, 52, 57/60 and 75 kDa were cross-linked to the 3′UTR. Supermobility shift assays indicated that PTB/hnRNP1 is part of this complex, and 3′UTR-crosslinked PTB/hnRNP1 was immunoprecipitated from HAstV-8 infected cell-membrane extracts. Also, immunofluorescence analyses revealed that PTB/hnRNP1 is distributed in the nucleus and cytoplasm of uninfected cells, but it is mainly localized perinuclearly in the cytoplasm of HAstV-8 infected cells. Furthermore, the minimal 3′UTR sequences recognized by recombinant PTB are those conforming helix I, and an intact PTB/hnRNP1-binding site. Finally, small interfering RNA-mediated PTB/hnRNP1 silencing reduced synthesis viral genome and virus yield in CaCo2 cells, suggesting that PTB/hnRNP1 is required for HAstV replication. In conclusion, PTB/hnRNP1 binds to the 3′UTR HAstV-8 and is required or participates in viral replication.",2014 Nov 18,"['Espinosa-Hernández, Wendy', 'Velez-Uriza, Dora', 'Valdés, Jesús', 'Vélez-Del Valle, Cristina', 'Salas-Benito, Juan', 'Martínez-Contreras, Rebeca', 'García-Espítia, Matilde', 'Salas-Benito, Mariana', 'Vega-Almeida, Tania', 'De Nova-Ocampo, Mónica']",PLoS One,,,True
60498316646f729173d57cac8d9c2cf9a701a2c9,PMC,Profiling bacterial community in upper respiratory tracts,http://dx.doi.org/10.1186/s12879-014-0583-3,PMC4236460,25391813,CC BY,"BACKGROUND: Infection by pathogenic viruses results in rapid epithelial damage and significantly impacts on the condition of the upper respiratory tract, thus the effects of viral infection may induce changes in microbiota. Thus, we aimed to define the healthy microbiota and the viral pathogen-affected microbiota in the upper respiratory tract. In addition, any association between the type of viral agent and the resultant microbiota profile was assessed. METHODS: We analyzed the upper respiratory tract bacterial content of 57 healthy asymptomatic people (17 health-care workers and 40 community people) and 59 patients acutely infected with influenza, parainfluenza, rhino, respiratory syncytial, corona, adeno, or metapneumo viruses using culture-independent pyrosequencing. RESULTS: The healthy subjects harbored primarily Streptococcus, whereas the patients showed an enrichment of Haemophilus or Moraxella. Quantifying the similarities between bacterial populations by using Fast UniFrac analysis indicated that bacterial profiles were apparently divisible into 6 oropharyngeal types in the tested subjects. The oropharyngeal types were not associated with the type of viruses, but were rather linked to the age of the subjects. Moraxella nonliquefaciens exhibited unprecedentedly high abundance in young subjects aged <6 years. The genome of M. nonliquefaciens was found to encode various proteins that may play roles in pathogenesis. CONCLUSIONS: This study identified 6 oropharyngeal microbiome types. No virus-specific bacterial profile was discovered, but comparative analysis of healthy adults and patients identified a bacterium specific to young patients, M. nonliquefaciens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0583-3) contains supplementary material, which is available to authorized users.",2014 Nov 13,"['Yi, Hana', 'Yong, Dongeun', 'Lee, Kyungwon', 'Cho, Yong-Joon', 'Chun, Jongsik']",BMC Infect Dis,,,True
408fb49191d282aa03d722d951eb500a1dde3b87,PMC,Carrageenan nasal spray in virus confirmed common cold: individual patient data analysis of two randomized controlled trials,http://dx.doi.org/10.1186/2049-6958-9-57,PMC4236476,25411637,CC BY,"BACKGROUND: Clinical trials applying iota-carrageenan nasal spray have previously shown to reduce duration of virus-confirmed common cold. The present study pooled data of two similar clinical trials to provide further evidence for the antiviral effectiveness of carrageenan. METHODS: Individual patient data were analyzed from two randomized double blind placebo controlled trials assessing the therapeutic effectiveness of carrageenan nasal spray in acute common cold. Patients with virus-confirmed common cold (n = 254, verum 126, placebo 128) were included and the following parameters were appraised: duration of disease, number of patients with relapses, number of respiratory viruses and viral titers at inclusion (visit 1) compared to days 3–5 (visit 2). RESULTS: Carrageenan treated patients showed a significant reduction in duration of disease of almost 2 days (p < 0.05) as well as significantly fewer relapses during 21 days of observation period (p < 0.05). The virus clearance between visit 1 and visit 2 was significantly more pronounced in the carrageenan group (p < 0.05). In both studies, virus-confirmed common cold was caused by three main virus subtypes: human rhinovirus (46%), human coronavirus (25%) and influenza A (14%) virus. Carrageenan nasal spray showed significant antiviral efficacy in all three virus subgroups, the highest effectiveness was observed in human corona virus-infected patients. The reduced duration of disease was 3 days (p < 0.01) and the number of relapses was three times less (p < 0.01) in carrageenan treated corona-virus-infected patients compared to control patients. CONCLUSIONS: Administration of carrageenan nasal spray in children as well as in adults suffering from virus-confirmed common cold reduced duration of disease, increased viral clearance and reduced relapses of symptoms. Carrageenan nasal spray appeared as an effective treatment of common cold in children and adults. TRIAL REGISTRATION: Pooled data from ISRCTN52519535 and ISRCTN80148028",2014 Nov 12,"['Koenighofer, Martin', 'Lion, Thomas', 'Bodenteich, Angelika', 'Prieschl-Grassauer, Eva', 'Grassauer, Andreas', 'Unger, Hermann', 'Mueller, Christian A', 'Fazekas, Tamás']",Multidiscip Respir Med,,,True
2934008a223a07e3fd3c886db120eb1fe3aab567,PMC,Respiratory virus is a real pathogen in immunocompetent community-acquired pneumonia: comparing to influenza like illness and volunteer controls,http://dx.doi.org/10.1186/1471-2466-14-144,PMC4236731,25178477,CC BY,"BACKGROUND: Viral pathogens were more commonly reported than previously estimated in community-acquired pneumonia (CAP) patients. However, the real role of virus was still controversial. METHODS: Consecutive adult patients with CAP between April and December, 2009 were prospectively enrolled. A four-fold or greater increase of IgG-titres against respiratory viruses in pair sera was tested by means of hemagglutination inhibition assay or indirect immunofluorescence. Swab samples were tested by cell culture and/or nucleic amplification tests. Viral etiology was considered definitive if at least one of the above tests was positive. RESULTS: Viral etiology was established in fifty-two (34.9%) of 149 CAP patients, twenty-two (81.5%) of 27 influenza like illness patients, and none of 75 volunteer controls. Forty-seven CAP patients were infected by a single virus (24 influenza A virus, 5 influenza B, 10 parainfluenza virus type 3 [PIV-3], 2 PIV-1, 2 adenovirus, 2 human rhinovirus and 2 coronavirus OC43), five cases by two or three viruses co-infection. Fever ≥ 39°C (66.7%), fatigue (64.6%), and purulent sputum (52.1%) was the most common symptoms in viral pneumonia patients. On multivariate analysis, myalgia was included in the model for pneumonia associated with influenza infection. In the CURB-65 model only influenza infection was found independently associated with severe disease (CURB-65 score ≥ 3) out of variables, including age(years), sex, current smoking status, sick contact with febrile patients, numbers of comorbidity, presence of influenza infection, presence of PIV infection, with P = 0.021, OR 7.86 (95% CI 1.37-45.04). CONCLUSION: Respiratory virus was not a bystander, but pathogenic in pneumonia and was a common cause of CAP.",2014 Sep 2,"['Zhan, Yangqing', 'Yang, Zifeng', 'Chen, Rongchang', 'Wang, Yutao', 'Guan, Wenda', 'Zhao, Suishan']",BMC Pulm Med,,,True
94c6aacd8aeb83b9798d43627bcf867944fb8afd,PMC,An eight-year epidemiologic study based on baculovirus-expressed type-specific spike proteins for the differentiation of type I and II feline coronavirus infections,http://dx.doi.org/10.1186/s12917-014-0186-7,PMC4236817,25123112,CC BY,"BACKGROUND: Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV). FCoVs are divided into two serotypes with markedly different infection rates among cat populations around the world. A baculovirus-expressed type-specific domain of the spike proteins of FCoV was used to survey the infection of the two viruses over the past eight years in Taiwan. RESULTS: An immunofluorescence assay based on cells infected with the recombinant viruses that was capable of distinguishing between the two types of viral infection was established. A total of 833 cases from a teaching hospital was surveyed for prevalence of different FCoV infections. Infection of the type I FCoV was dominant, with a seropositive rate of 70.4%, whereas 3.5% of cats were infected with the type II FCoV. In most cases, results derived from serotyping and genotyping were highly agreeable. However, 16.7% (4/24) FIP cats and 9.8% (6/61) clinically healthy cats were found to possess antibodies against both viruses. Moreover, most of the cats (84.6%, 22/26) infected with a genotypic untypable virus bearing a type I FCoV antibody. CONCLUSION: A relatively simple serotyping method to distinguish between two types of FCoV infection was developed. Based on this method, two types of FCoV infection in Taiwan was first carried out. Type I FCoV was found to be predominant compared with type II virus. Results derived from serotyping and genotyping support our current understanding of evolution of disease-related FCoV and transmission of FIP.",2014 Aug 15,"['Wang, Ying-Ting', 'Chueh, Ling-Ling', 'Wan, Cho-Hua']",BMC Vet Res,,,True
d7a80f6f56131be32a661d7604b38c6a893ded50,PMC,CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection,http://dx.doi.org/10.1371/journal.pone.0112060,PMC4237331,25409519,CC0,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors.",2014 Nov 19,"['Caì, Yíngyún', 'Yú, Shuǐqìng', 'Postnikova, Elena N.', 'Mazur, Steven', 'Bernbaum, John G.', 'Burk, Robin', 'Zhāng, Téngfēi', 'Radoshitzky, Sheli R.', 'Müller, Marcel A.', 'Jordan, Ingo', 'Bollinger, Laura', 'Hensley, Lisa E.', 'Jahrling, Peter B.', 'Kuhn, Jens H.']",PLoS One,,,True
f87c8bfc787731a80acd6bf082c748c41afb8a4a,PMC,Frequency and Fitness Consequences of Bacteriophage Φ6 Host Range Mutations,http://dx.doi.org/10.1371/journal.pone.0113078,PMC4237377,25409341,CC BY,"Viruses readily mutate and gain the ability to infect novel hosts, but few data are available regarding the number of possible host range-expanding mutations allowing infection of any given novel host, and the fitness consequences of these mutations on original and novel hosts. To gain insight into the process of host range expansion, we isolated and sequenced 69 independent mutants of the dsRNA bacteriophage Φ6 able to infect the novel host, Pseudomonas pseudoalcaligenes. In total, we found at least 17 unique suites of mutations among these 69 mutants. We assayed fitness for 13 of 17 mutant genotypes on P. pseudoalcaligenes and the standard laboratory host, P. phaseolicola. Mutants exhibited significantly lower fitnesses on P. pseudoalcaligenes compared to P. phaseolicola. Furthermore, 12 of the 13 assayed mutants showed reduced fitness on P. phaseolicola compared to wildtype Φ6, confirming the prevalence of antagonistic pleiotropy during host range expansion. Further experiments revealed that the mechanistic basis of these fitness differences was likely variation in host attachment ability. In addition, using computational protein modeling, we show that host-range expanding mutations occurred in hotspots on the surface of the phage's host attachment protein opposite a putative hydrophobic anchoring domain.",2014 Nov 19,"['Ford, Brian E.', 'Sun, Bruce', 'Carpino, James', 'Chapler, Elizabeth S.', 'Ching, Jane', 'Choi, Yoon', 'Jhun, Kevin', 'Kim, Jung D.', 'Lallos, Gregory G.', 'Morgenstern, Rachelle', 'Singh, Shalini', 'Theja, Sai', 'Dennehy, John J.']",PLoS One,,,True
cbe56b09d64047cba4ee7875c4f55276a0cdf273,PMC,Enterovirus 71-induced autophagy increases viral replication and pathogenesis in a suckling mouse model,http://dx.doi.org/10.1186/s12929-014-0080-4,PMC4237791,25139436,CC BY,"BACKGROUND: We previously reported that Enterovirus 71 (EV71) infection activates autophagy, which promotes viral replication both in vitro and in vivo. In the present study we further investigated whether EV71 infection of neuronal SK-N-SH cells induces an autophagic flux. Furthermore, the effects of autophagy on EV71-related pathogenesis and viral load were evaluated after intracranial inoculation of mouse-adapted EV71 (MP4 strain) into 6-day-old ICR suckling mice. RESULTS: We demonstrated that in EV71-infected SK-N-SH cells, EV71 structural protein VP1 and nonstructural protein 2C co-localized with LC3 and mannose-6-phosphate receptor (MPR, endosome marker) proteins by immunofluorescence staining, indicating amphisome formation. Together with amphisome formation, EV71 induced an autophagic flux, which could be blocked by NH(4)Cl (inhibitor of acidification) and vinblastine (inhibitor of fusion), as demonstrated by Western blotting. Suckling mice intracranially inoculated with EV71 showed EV71 VP1 protein expression (representing EV71 infection) in the cerebellum, medulla, and pons by immunohistochemical staining. Accompanied with these infected brain tissues, increased expression of LC3-II protein as well as formation of LC3 aggregates, autophagosomes and amphisomes were detected. Amphisome formation, which was confirmed by colocalization of EV71-VP1 protein or LC3 puncta and the endosome marker protein MPR. Thus, EV71-infected suckling mice (similar to EV71-infected SK-N-SH cells) also show an autophagic flux. The physiopathological parameters of EV71-MP4 infected mice, including body weight loss, disease symptoms, and mortality were increased compared to those of the uninfected mice. We further blocked EV71-induced autophagy with the inhibitor 3-methyladenine (3-MA), which attenuated the disease symptoms and decreased the viral load in the brain tissues of the infected mice. CONCLUSIONS: In this study, we reveal that EV71 infection of suckling mice induces an amphisome formation accompanied with the autophagic flux in the brain tissues. Autophagy induced by EV71 promotes viral replication and EV71-related pathogenesis.",2014 Aug 20,"['Lee, Ying-Ray', 'Wang, Po-Shun', 'Wang, Jen-Ren', 'Liu, Hsiao-Sheng']",J Biomed Sci,,,True
2f00227d35cee08706713c7085ec576b74ff2f9a,PMC,Is There Still Room for Novel Viral Pathogens in Pediatric Respiratory Tract Infections?,http://dx.doi.org/10.1371/journal.pone.0113570,PMC4239085,25412469,CC BY,"Viruses are the most frequent cause of respiratory disease in children. However, despite the advanced diagnostic methods currently in use, in 20 to 50% of respiratory samples a specific pathogen cannot be detected. In this work, we used a metagenomic approach and deep sequencing to examine respiratory samples from children with lower and upper respiratory tract infections that had been previously found negative for 6 bacteria and 15 respiratory viruses by PCR. Nasal washings from 25 children (out of 250) hospitalized with a diagnosis of pneumonia and nasopharyngeal swabs from 46 outpatient children (out of 526) were studied. DNA reads for at least one virus commonly associated to respiratory infections was found in 20 of 25 hospitalized patients, while reads for pathogenic respiratory bacteria were detected in the remaining 5 children. For outpatients, all the samples were pooled into 25 DNA libraries for sequencing. In this case, in 22 of the 25 sequenced libraries at least one respiratory virus was identified, while in all other, but one, pathogenic bacteria were detected. In both patient groups reads for respiratory syncytial virus, coronavirus-OC43, and rhinovirus were identified. In addition, viruses less frequently associated to respiratory infections were also found. Saffold virus was detected in outpatient but not in hospitalized children. Anellovirus, rotavirus, and astrovirus, as well as several animal and plant viruses were detected in both groups. No novel viruses were identified. Adding up the deep sequencing results to the PCR data, 79.2% of 250 hospitalized and 76.6% of 526 ambulatory patients were positive for viruses, and all other children, but one, had pathogenic respiratory bacteria identified. These results suggest that at least in the type of populations studied and with the sampling methods used the odds of finding novel, clinically relevant viruses, in pediatric respiratory infections are low.",2014 Nov 20,"['Taboada, Blanca', 'Espinoza, Marco A.', 'Isa, Pavel', 'Aponte, Fernando E.', 'Arias-Ortiz, María A.', 'Monge-Martínez, Jesús', 'Rodríguez-Vázquez, Rubén', 'Díaz-Hernández, Fidel', 'Zárate-Vidal, Fernando', 'Wong-Chew, Rosa María', 'Firo-Reyes, Verónica', 'del Río-Almendárez, Carlos N.', 'Gaitán-Meza, Jesús', 'Villaseñor-Sierra, Alberto', 'Martínez-Aguilar, Gerardo', 'Salas-Mier, Ma. del Carmen', 'Noyola, Daniel E.', 'Pérez-Gónzalez, Luis F.', 'López, Susana', 'Santos-Preciado, José I.', 'Arias, Carlos F.']",PLoS One,,,True
2402b2a0cb8aef3abb2e103f0997c61dec6511a0,PMC,Full-Genome Sequence Analysis of a Variant Strain of Porcine Epidemic Diarrhea Virus in South Korea,http://dx.doi.org/10.1128/genomeA.01116-14,PMC4239346,25414491,CC BY,"In March of 2014, a variant of novel porcine epidemic diarrhea virus (PEDV) was first identified in South Korea and found to be most closely related to the U.S. variant strain OH851. The complete genome of the KOR/KNU-1406/2014 strain was sequenced and analyzed to investigate the U.S.-strain-like variant circulating in South Korea.",2014 Nov 20,"['Lee, Sunhee', 'Park, Gun-Seok', 'Shin, Jae-Ho', 'Lee, Changhee']",Genome Announc,,,True
63771fc756683bf14c7f7e169990c7268b35d8ed,PMC,The discriminative capacity of soluble Toll-like receptor (sTLR)2 and sTLR4 in inflammatory diseases,http://dx.doi.org/10.1186/s12865-014-0055-y,PMC4240815,25406630,CC BY,"BACKGROUND: The extracellular domains of cytokine receptors are released during inflammation, but little is known about the shedding of Toll-like receptors (TLR) and whether they can be used as diagnostic biomarkers. METHODS: The release of sTLR2 and sTLR4 was studied in in-vitro stimulations, as well as in-vivo during experimental human endotoxemia (n = 11, 2 ng/kg LPS), and in plasma of 394 patients with infections (infectious mononucleosis, measles, respiratory tract infections, bacterial sepsis and candidemia) or non-infectious inflammation (Crohn’s disease, gout, rheumatoid arthritis, autoinflammatory syndromes and pancreatitis). Using C-statistics, the value of sTLR2 and sTLR4 levels for discrimination between infections and non-infectious inflammatory diseases, as well as between viral and bacterial infections was analyzed. RESULTS: In-vitro, peripheral blood mononuclear cells released sTLR2 and sTLR4 by exposure to microbial ligands. During experimental human endotoxemia, plasma concentrations peaked after 2 hours (sTLR4) and 4 hours (sTLR2). sTLR4 did not correlate with cytokines, but sTLR2 correlated positively with TNFα (r(s) = 0.80, P < 0.05), IL-6 (r(s) = 0.65, P < 0.05), and IL-1Ra (r(s) = 0.57, P = 0.06), and negatively with IL-10 (r(s) = -0.58, P = 0.06), respectively. sTLR4 had a similar area under the ROC curve [AUC] for differentiating infectious and non-infectious inflammation compared to CRP: 0.72 (95% CI 0.66-0.79) versus 0.74 (95% CI 0.69-0.80) [P = 0.80], while sTLR2 had a lower AUC: 0.60 (95% CI 0.54-0.66) [P = 0.0004]. CRP differentiated bacterial infections better from viral infections than sTLR2 and sTLR4: AUC 0.94 (95% CI 0.90-0.96) versus 0.58 (95% CI 0.51-0.64) and 0.75 (95% CI 0.70-0.80), respectively [P < 0.0001 for both]. CONCLUSIONS: sTLRs are released into the circulation, and suggest the possibility to use sTLRs as diagnostic tool in inflammatory conditions.",2014 Nov 19,"['ten Oever, Jaap', 'Kox, Matthijs', 'van de Veerdonk, Frank L', 'Mothapo, Khutso M', 'Slavcovici, Adriana', 'Jansen, Tim L', 'Tweehuysen, Lieke', 'Giamarellos-Bourboulis, Evangelos J', 'Schneeberger, Peter M', 'Wever, Peter C', 'Stoffels, Monique', 'Simon, Anna', 'van der Meer, Jos WM', 'Johnson, Melissa D', 'Kullberg, Bart-Jan', 'Pickkers, Peter', 'Pachot, Alexandre', 'Joosten, Leo AB', 'Netea, Mihai G']",BMC Immunol,,,True
8b47882ebbc8d2e9d217dcc10b2328eff5bf8b46,PMC,Cell Surface Protein Disulfide Isomerase Regulates Natriuretic Peptide Generation of Cyclic Guanosine Monophosphate,http://dx.doi.org/10.1371/journal.pone.0112986,PMC4242536,25419565,CC BY,"RATIONALE: The family of natriuretic peptides (NPs), including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), exert important and diverse actions for cardiovascular and renal homeostasis. The autocrine and paracrine functions of the NPs are primarily mediated through the cellular membrane bound guanylyl cyclase-linked receptors GC-A (NPR-A) and GC-B (NPR-B). As the ligands and receptors each contain disulfide bonds, a regulatory role for the cell surface protein disulfide isomerase (PDI) was investigated. OBJECTIVE: We utilized complementary in vitro and in vivo models to determine the potential role of PDI in regulating the ability of the NPs to generate its second messenger, cyclic guanosine monophosphate. METHODS AND RESULTS: Inhibition of PDI attenuated the ability of ANP, BNP and CNP to generate cGMP in human mesangial cells (HMCs), human umbilical vein endothelial cells (HUVECs), and human aortic smooth muscle cells (HASMCs), each of which were shown to express PDI. In LLC-PK1 cells, where PDI expression was undetectable by immunoblotting, PDI inhibition had a minimal effect on cGMP generation. Addition of PDI to cultured LLC-PK1 cells increased intracellular cGMP generation mediated by ANP. Inhibition of PDI in vivo attenuated NP-mediated generation of cGMP by ANP. Surface Plasmon Resonance demonstrated modest and differential binding of the natriuretic peptides with immobilized PDI in a cell free system. However, PDI was shown to co-localize on the surface of cells with GC-A and GC-B by co-immunoprecpitation and immunohistochemistry. CONCLUSION: These data demonstrate for the first time that cell surface PDI expression and function regulate the capacity of natriuretic peptides to generate cGMP through interaction with their receptors.",2014 Nov 24,"['Pan, Shuchong', 'Chen, Horng H.', 'Correia, Cristina', 'Dai, Haiming', 'Witt, Tyra A.', 'Kleppe, Laurel S.', 'Burnett, John C.', 'Simari, Robert D.']",PLoS One,,,True
98157c4866587f2ad65dbf57f6a7cb5a7699b1e4,PMC,A clinical prediction rule for diagnosing human infections with avian influenza A(H7N9) in a hospital emergency department setting,http://dx.doi.org/10.1186/s12916-014-0127-0,PMC4243192,25091477,CC BY,"BACKGROUND: Human infections with avian influenza A(H7N9) virus are associated with severe illness and high mortality. To better inform triage decisions of hospitalization and management, we developed a clinical prediction rule for diagnosing patients with A(H7N9) and determined its predictive performance. METHODS: Clinical details on presentation of adult patients hospitalized with either A(H7N9)(n = 121) in China from March to May 2013 or other causes of acute respiratory infections (n = 2,603) in Jingzhou City, China from January 2010 through September 2012 were analyzed. A clinical prediction rule was developed using a two-step coefficient-based multivariable logistic regression scoring method and evaluated with internal validation by bootstrapping. RESULTS: In step 1, predictors for A(H7N9) included male sex, poultry exposure history, and fever, haemoptysis, or shortness of breath on history and physical examination. In step 2, haziness or pneumonic consolidation on chest radiographs and leukopenia were also associated with a higher probability of A(H7N9). The observed risk of A(H7N9) was 0.3% for those assigned to the low-risk group and 2.5%, 4.3%, and 44.0% for tertiles 1 through 3, respectively, in the high-risk group. This prediction rule achieved good model performance, with an optimism-corrected sensitivity of 0.93, a specificity of 0.80, and an area under the receiver-operating characteristic curve of 0.96. CONCLUSIONS: A simple decision rule based on data readily obtainable in the setting of patients’ first clinical presentations from the first wave of the A/H7N9 epidemic in China has been developed. This prediction rule has achieved good model performance in predicting their risk of A(H7N9) infection and should be useful in guiding important clinical and public health decisions in a timely and objective manner. Data to be gathered with its use in the current evolving second wave of the A/H7N9 epidemic in China will help to inform its performance in the field and contribute to its further refinement. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-014-0127-0) contains supplementary material, which is available to authorized users.",2014 Aug 5,"['Liao, Qiaohong', 'Ip, Dennis K M', 'Tsang, Tim K', 'Cao, Bin', 'Jiang, Hui', 'Liu, Fengfeng', 'Zheng, Jiandong', 'Peng, Zhibin', 'Wu, Peng', 'Huai, Yang', 'Lau, Eric H Y', 'Feng, Luzhao', 'Leung, Gabriel M', 'Yu, Hongjie', 'Cowling, Benjamin J']",BMC Med,,,False
3a4cf1cc2f583dea77288aa7e114c117a00660b2,PMC,A clinical prediction rule for diagnosing human infections with avian influenza A(H7N9) in a hospital emergency department setting,http://dx.doi.org/10.1186/s12916-014-0127-0,PMC4243192,25091477,CC BY,"BACKGROUND: Human infections with avian influenza A(H7N9) virus are associated with severe illness and high mortality. To better inform triage decisions of hospitalization and management, we developed a clinical prediction rule for diagnosing patients with A(H7N9) and determined its predictive performance. METHODS: Clinical details on presentation of adult patients hospitalized with either A(H7N9)(n = 121) in China from March to May 2013 or other causes of acute respiratory infections (n = 2,603) in Jingzhou City, China from January 2010 through September 2012 were analyzed. A clinical prediction rule was developed using a two-step coefficient-based multivariable logistic regression scoring method and evaluated with internal validation by bootstrapping. RESULTS: In step 1, predictors for A(H7N9) included male sex, poultry exposure history, and fever, haemoptysis, or shortness of breath on history and physical examination. In step 2, haziness or pneumonic consolidation on chest radiographs and leukopenia were also associated with a higher probability of A(H7N9). The observed risk of A(H7N9) was 0.3% for those assigned to the low-risk group and 2.5%, 4.3%, and 44.0% for tertiles 1 through 3, respectively, in the high-risk group. This prediction rule achieved good model performance, with an optimism-corrected sensitivity of 0.93, a specificity of 0.80, and an area under the receiver-operating characteristic curve of 0.96. CONCLUSIONS: A simple decision rule based on data readily obtainable in the setting of patients’ first clinical presentations from the first wave of the A/H7N9 epidemic in China has been developed. This prediction rule has achieved good model performance in predicting their risk of A(H7N9) infection and should be useful in guiding important clinical and public health decisions in a timely and objective manner. Data to be gathered with its use in the current evolving second wave of the A/H7N9 epidemic in China will help to inform its performance in the field and contribute to its further refinement. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-014-0127-0) contains supplementary material, which is available to authorized users.",2014 Aug 5,"['Liao, Qiaohong', 'Ip, Dennis K M', 'Tsang, Tim K', 'Cao, Bin', 'Jiang, Hui', 'Liu, Fengfeng', 'Zheng, Jiandong', 'Peng, Zhibin', 'Wu, Peng', 'Huai, Yang', 'Lau, Eric H Y', 'Feng, Luzhao', 'Leung, Gabriel M', 'Yu, Hongjie', 'Cowling, Benjamin J']",BMC Med,,,True
72b6e571746493f62630cc8eb59cd6fae5cb71e2,PMC,The pathological effects of CCR2+ inflammatory monocytes are amplified by an IFNAR1-triggered chemokine feedback loop in highly pathogenic influenza infection,http://dx.doi.org/10.1186/s12929-014-0099-6,PMC4243311,25407417,CC BY,"BACKGROUND: Highly pathogenic influenza viruses cause high levels of morbidity, including excessive infiltration of leukocytes into the lungs, high viral loads and a cytokine storm. However, the details of how these pathological features unfold in severe influenza infections remain unclear. Accumulation of Gr1 + CD11b + myeloid cells has been observed in highly pathogenic influenza infections but it is not clear how and why they accumulate in the severely inflamed lung. In this study, we selected this cell population as a target to investigate the extreme inflammatory response during severe influenza infection. RESULTS: We established H1N1 IAV-infected mouse models using three viruses of varying pathogenicity and noted the accumulation of a defined Gr1 + CD11b + myeloid population correlating with the pathogenicity. Herein, we reported that CCR2+ inflammatory monocytes are the major cell compartments in this population. Of note, impaired clearance of the high pathogenicity virus prolonged IFN expression, leading to CCR2+ inflammatory monocytes amplifying their own recruitment via an interferon-α/β receptor 1 (IFNAR1)-triggered chemokine loop. Blockage of IFNAR1-triggered signaling or inhibition of viral replication by Oseltamivir significantly suppresses the expression of CCR2 ligands and reduced the influx of CCR2+ inflammatory monocytes. Furthermore, trafficking of CCR2+ inflammatory monocytes from the bone marrow to the lung was evidenced by a CCR2-dependent chemotaxis. Importantly, leukocyte infiltration, cytokine storm and expression of iNOS were significantly reduced in CCR2−/− mice lacking infiltrating CCR2+ inflammatory monocytes, enhancing the survival of the infected mice. CONCLUSIONS: Our results indicated that uncontrolled viral replication leads to excessive production of inflammatory innate immune responses by accumulating CCR2+ inflammatory monocytes, which contribute to the fatal outcomes of high pathogenicity virus infections.",2014 Nov 18,"['Lin, Sue-Jane', 'Lo, Ming', 'Kuo, Rei-Lin', 'Shih, Shin-Ru', 'Ojcius, David M', 'Lu, Jean', 'Lee, Chien-Kuo', 'Chen, Hui-Chen', 'Lin, Meei Yun', 'Leu, Chuen-Miin', 'Lin, Chia-Ni', 'Tsai, Ching-Hwa']",J Biomed Sci,,,True
6ca67d203ed9f4870c85f2289d62ee3c498b5a13,PMC,Imaging analysis of human metapneumovirus-infected cells provides evidence for the involvement of F-actin and the raft-lipid microdomains in virus morphogenesis,http://dx.doi.org/10.1186/s12985-014-0198-8,PMC4243936,25408253,CC BY,"BACKGOUND: Due to difficulties of culturing Human metapneumovirus (HMPV) much of the current understanding of HMPV replication can be inferred from other closely related viruses. The slow rates of virus replication prevent many biochemical analyses of HMPV particles. In this study imaging was used to examine the process of HMPV morphogenesis in individually infected LLC-MK2 cells, and to better characterise the sites of HMPV assembly. This strategy has circumvented the problems associated with slow replication rates and allowed us to characterise both the HMPV particles and the sites of HMPV morphogenesis. METHODS: HMPV-infected LLC-MK2 cells were stained with antibodies that recognised the HMPV fusion protein (F protein), attachment protein (G protein) and matrix protein (M protein), and fluorescent probes that detect GM1 within lipid-raft membranes (CTX-B-AF488) and F-actin (Phalloidin-FITC). The stained cells were examined by confocal microscopy, which allowed imaging of F-actin, GM1 and virus particles in HMPV-infected cells. Cells co-expressing recombinant HMPV G and F proteins formed virus-like particles and were co-stained with antibodies that recognise the recombinant G and F proteins and phalloidin-FITC and CTX-B-AF594, and the distribution of the G and F proteins, GM1 and F-actin determined. RESULTS: HMPV-infected cells stained with anti-F, anti-G or anti-M revealed a filamentous staining pattern, indicating that the HMPV particles have a filamentous morphology. Staining of HMPV-infected cells with anti-G and either phalloidin-FITC or CTX-B-AF488 exhibited extensive co-localisation of these cellular probes within the HMPV filaments. This suggested that lipid-raft membrane domains and F-actin structures are present at the site of the virus morphogenesis, and are subsequently incorporated into the HMPV filaments. Furthermore, the filamentous virus-like particles that form in cells expressing the G protein formed in cellular structures containing GM1 and F-actin, suggesting the G protein contains intrinsic targeting signals to the sites of virus assembly. CONCLUSIONS: These data suggest that HMPV matures as filamentous particles and that virus morphogenesis occurs within lipid-raft microdomains containing localized concentrations of F-actin. The similarity between HMPV morphogenesis and the closely related human respiratory syncytial virus suggests that involvement of F-actin and lipid-raft microdomains in virus morphogenesis may be a common feature of the Pneumovirinae. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-014-0198-8) contains supplementary material, which is available to authorized users.",2014 Nov 19,"['Jumat, Muhammad Raihan', 'Nguyen Huong, Tra', 'Wong, Puisan', 'Loo, Liat Hui', 'Tan, Boon Huan', 'Fenwick, Fiona', 'Toms, Geoffrey L', 'Sugrue, Richard J']",Virol J,,,True
f5b706d0529bfcf7e2d1dfc037df5b6f95fc5ec0,PMC,Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study,http://dx.doi.org/10.1186/s13054-014-0456-6,PMC4243941,25112957,CC BY,"INTRODUCTION: Since 2008, severe cases of emerging human adenovirus type 55 (HAdV-55) in immunocompetent adults have been reported sporadically in China. The clinical features and outcomes of the most critically ill patients with severe acute respiratory distress syndrome (ARDS) caused by HAdV-55 requiring invasive mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation (ECMO) are lacking. METHODS: We conducted a prospective, single-center observational study of pneumonia with ARDS in immunocompetent adults admitted to our respiratory ICU. We prospectively collected and analyzed clinical, laboratory, radiological characteristics, sequential tests of viral load in respiratory tract and blood, treatments and outcomes. RESULTS: The results for a total of five consecutive patients with severe ARDS with confirmed HAdV-55 infection were included. All five patients were immunocompetent young men with a median age of 32 years. The mean time from onset to dyspnea was 5 days. Arterial blood gas analysis at ICU admission revealed profound hypoxia. Mean partial oxygen pressure/fraction of inspired oxygen was 58.1. Mean durations from onset to a single-lobe consolidation shown on chest X-rays (CXRs) and, from the first positive CXR to bilateral multilobar lung infiltrates, were 2 days and 4.8 days, respectively. The viral load was higher than 1 × 10(8) copies in three patients and was 1 × 10(4) in one patient. It was negative in the only patient who survived. The mean duration for noninvasive positive pressure ventilation (NPPV) failure and IMV failure were 30.8 hours and 6.2 days, respectively. Four patients received venovenous ECMO. Four (80%) of the five patients died despite receiving appropriate respiratory support. CONCLUSIONS: HAdV-55 may cause severe ARDS in immunocompetent young men. Persistent high fever, dyspnea and rapid progression to respiratory failure within 2 weeks, together with bilateral consolidations and infiltrates, are the most frequent clinical manifestations of HAdV-55-induced severe ARDS. Viral load monitoring may help predict disease severity and outcome. The NPPV and IMV failure rates were very high, but ECMO may still be the respiratory support therapy of choice. TRIAL REGISTRATION: Clinicaltrials.gov NCT01585922. Registered 20 April 2012",2014 Aug 12,"['Sun, Bing', 'He, Hangyong', 'Wang, Zheng', 'Qu, Jiuxin', 'Li, Xuyan', 'Ban, Chengjun', 'Wan, Jun', 'Cao, Bin', 'Tong, Zhaohui', 'Wang, Chen']",Crit Care,,,True
a1a6c0067edf3605299df62d104c31661bbccaec,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,True
67f6981719f5f6d229ac5ff46e353bb7cb1aaea3,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
0bbb3db3fcea884e703a8ab09176b0b6305a6620,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
32ae76810277fb989a7cbc203079b2ae5bc13c2b,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
e26afacc53f34a9432daf809891b5e519f6c1047,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
464a5110126b27bb1e70948714cef5c8528c2c9e,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
1ea345b58fb3fa32d7fbeaf3e6c236ab6a104abe,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
c17d7f1607f8fa333c799b263c8185d3b3d369ac,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
f67740f11517f204388333d646050566bba9b65b,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
bee2faef06dd2aefa2a126de2e15cbe403562aae,PMC,Comparison of Contact Patterns Relevant for Transmission of Respiratory Pathogens in Thailand and the Netherlands Using Respondent-Driven Sampling,http://dx.doi.org/10.1371/journal.pone.0113711,PMC4244136,25423343,CC BY,"Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand.",2014 Nov 25,"['Stein, Mart L.', 'van Steenbergen, Jim E.', 'Buskens, Vincent', 'van der Heijden, Peter G. M.', 'Chanyasanha, Charnchudhi', 'Tipayamongkholgul, Mathuros', 'Thorson, Anna E.', 'Bengtsson, Linus', 'Lu, Xin', 'Kretzschmar, Mirjam E. E.']",PLoS One,,,False
063f48cf2d9b53b075433f3bd1a63566feb240db,PMC,"Spatial Analysis of the Distribution, Risk Factors and Access to Medical Resources of Patients with Hepatitis B in Shenzhen, China",http://dx.doi.org/10.3390/ijerph111111505,PMC4245626,25386954,CC BY,"Considering the high morbidity of hepatitis B in China, many epidemiological studies based on classic medical statistical analysis have been started but lack spatial information. However, spatial information such as the spatial distribution, autocorrelation and risk factors of the disease is of great help in studying patients with hepatitis B. This study examined 2851 cases of hepatitis B that were hospitalized in Shenzhen in 2010 and studied the spatial distribution, risk factors and spatial access to health services using spatial interpolation, Pearson correlation analysis and the improved two-step floating catchment area method. The results showed that the spatial distribution of hepatitis B, along with risk factors as well as spatial access to the regional medical resources, was uneven and mainly concentrated in the south and southwest of Shenzhen in 2010. In addition, the distribution characteristics of hepatitis B revealed a positive correlation between four types of service establishments and risk factors for the disease. The Pearson correlation coefficients are 0.566, 0.515, 0.626, 0.538 corresponding to bath centres, beauty salons, massage parlours and pedicure parlours (p < 0.05). Additionally, the allocation of medical resources for hepatitis B is adequate, as most patients could be treated at nearby hospitals.",2014 Nov 7,"['Xi, Yuliang', 'Ren, Fu', 'Liang, Shi', 'Zhang, Jinghua', 'Lin, De-Nan']",Int J Environ Res Public Health,,,True
4b6c86374fd6b66e8d0729a9d32d7cf6a11be71e,PMC,Complete Genome Characterization of Korean Porcine Deltacoronavirus Strain KOR/KNU14-04/2014,http://dx.doi.org/10.1128/genomeA.01191-14,PMC4246158,25428966,CC BY,"In April 2014, porcine deltacoronavirus (PDCoV) was first identified in feces from diarrheic piglets in South Korea and found to be closely related to other PDCoV strains. The complete genome of the Korean PDCoV strain, KOR/KNU14-04/2014, was sequenced and analyzed to characterize PDCoV circulating in South Korea.",2014 Nov 26,"['Lee, Sunhee', 'Lee, Changhee']",Genome Announc,,,True
6b1560c20661e5dea1c1d2c391c1fa68f6cf83ca,PMC,Advances in prevention and therapy of neonatal dairy calf diarrhoea: a systematical review with emphasis on colostrum management and fluid therapy,http://dx.doi.org/10.1186/s13028-014-0075-x,PMC4246539,25431305,CC BY,"Neonatal calf diarrhoea remains the most common cause of morbidity and mortality in preweaned dairy calves worldwide. This complex disease can be triggered by both infectious and non-infectious causes. The four most important enteropathogens leading to neonatal dairy calf diarrhoea are Escherichia coli, rota- and coronavirus, and Cryptosporidium parvum. Besides treating diarrhoeic neonatal dairy calves, the veterinarian is the most obvious person to advise the dairy farmer on prevention and treatment of this disease. This review deals with prevention and treatment of neonatal dairy calf diarrhoea focusing on the importance of a good colostrum management and a correct fluid therapy.",2014 Nov 25,"['Meganck, Vanessa', 'Hoflack, Geert', 'Opsomer, Geert']",Acta Vet Scand,,,True
8dd45f6f44956863508e44c1e6c7338b51a7524d,PMC,Characterizing Influenza surveillance systems performance: application of a Bayesian hierarchical statistical model to Hong Kong surveillance data,http://dx.doi.org/10.1186/1471-2458-14-850,PMC4246552,25127906,CC BY,"BACKGROUND: Infectious disease surveillance is a process the product of which reflects both actual disease trends and public awareness of the disease. Decisions made by patients, health care providers, and public health professionals about seeking and providing health care and about reporting cases to health authorities are all influenced by the information environment, which changes constantly. Biases are therefore imbedded in surveillance systems; these biases need to be characterized to provide better situational awareness for decision-making purposes. Our goal is to develop a statistical framework to characterize influenza surveillance systems, particularly their correlation with the information environment. METHODS: We identified Hong Kong influenza surveillance data systems covering healthcare providers, laboratories, daycare centers and residential care homes for the elderly. A Bayesian hierarchical statistical model was developed to examine the statistical relationships between the influenza surveillance data and the information environment represented by alerts from HealthMap and web queries from Google. Different models were fitted for non-pandemic and pandemic periods and model goodness-of-fit was assessed using common model selection procedures. RESULTS: Some surveillance systems — especially ad hoc systems developed in response to the pandemic flu outbreak — are more correlated with the information environment than others. General practitioner (percentage of influenza-like-illness related patient visits among all patient visits) and laboratory (percentage of specimen tested positive) seem to proportionally reflect the actual disease trends and are less representative of the information environment. Surveillance systems using influenza-specific code for reporting tend to reflect biases of both healthcare seekers and providers. CONCLUSIONS: This study shows certain influenza surveillance systems are less correlated with the information environment than others, and therefore, might represent more reliable indicators of disease activity in future outbreaks. Although the patterns identified in this study might change in future outbreaks, the potential susceptibility of surveillance data is likely to persist in the future, and should be considered when interpreting surveillance data. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-850) contains supplementary material, which is available to authorized users.",2014 Aug 15,"['Zhang, Ying', 'Arab, Ali', 'Cowling, Benjamin J', 'Stoto, Michael A']",BMC Public Health,,,True
f66963a9155d44a7f734c0f1d30cab3371cd99fa,PMC,Comparative serum proteome expression of the steroid-induced femoral head osteonecrosis in adults,http://dx.doi.org/10.3892/etm.2014.2069,PMC4247312,25452779,CC BY,"Steroid-induced osteonecrosis of the femoral head (SONFH) is a disabling, aseptic and ischemic disease that develops following steroid therapy. The pathogenesis of SONFH is unclear, so the early diagnosis and treatment for this disease is yet to be established. The purpose of the present study was to identify potential biomarkers for SONFH. The differential expression of serum proteins from patients with SONFH and healthy volunteers was analyzed by the proteomics method. The protein samples were labeled and subjected to isoelectric focusing and two-dimensional gel electrophoresis. The resultant protein spots were matched and quantified by an imaging analysis system. The differentially-expressed protein spots were subjected to in-gel trypsin digestion followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Significantly lower levels of complement component 3 (C3), C4, inter-α-trypsin inhibitor heavy chain H4 and α-2-macroglobulin were found in the serum of patients with SONFH. These proteins are reported to be actively involved in intravascular coagulation, apoptosis and reactive oxygen species imbalance, indicating that multiple pathological reactions occur in SONFH and these proteins may serve as potential biomarkers for the diagnosis of SONFH.",2015 Jan 12,"['CHEN, YUXIAN', 'ZENG, CHUN', 'ZENG, HUA', 'ZHANG, RONGKAI', 'YE, ZHIQIANG', 'XING, BANGRONG', 'HU, KUNHUA', 'LI, MINGTAO', 'CAI, DAO ZHANG']",Exp Ther Med,,,True
8fcf1d545d5c10fbe83bbbd9dab8391fb748be7f,PMC,The ability to suppress macrophage-mediated inflammation in orbital fat stem cells is controlled by miR-671-5p,http://dx.doi.org/10.1186/scrt486,PMC4247678,25124290,CC BY,"INTRODUCTION: Our previous works demonstrated that systemic orbital fat-derived stem cell (OFSC) transplantation was effective in ameliorating lipopolysaccharide (LPS)-induced extensive acute lung injury (ALI) in vivo mainly through paracrine regulation of macrophage-mediated cytokine-storm. In this study, we explore the molecular mechanism(s) of OFSCs regulating macrophage activity in a cytokine-inducible fashion. METHODS: LPS (100 ng/ml)-activated macrophages were treated by conditioned medium from OFSCs (OFSCs-CM) or non-contact cultured with OFSCs for 6 hours. The potency of OFSCs on macrophage proliferation and pro-inflammation ability were determined. Expression levels of pro-inflammatory cytokines in macrophages, inducible immuno-modulatory factors in OFSCs, were investigated. Deep sequencing analysis as well as interaction between microRNA (miRNA) and genes of immuno-modulators in OFSCs induced by activated macrophages was predicted by miRTar. Transfection of miRNA inhibitor into OFSCs was performed. Real-time RT-PCR and transplantation of OFSCs into mice with LPS-induced ALI confirmed the in vitro and in vivo mechanism. RESULTS: The paracrine effect of OFSCs on inhibition of macrophage pro-inflammatory cytokine release was more potent than induction of macrophage G0/G1 cell cycle arrest. OFSCs-CM suppressed LPS-induced inducible nitric oxide synthetase and the pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1 alpha, and IL-1 beta expression in macrophages. Under non-contact culture, LPS-activated macrophages effectively triggered the expression of soluble immuno-modulating factors in OFSCs, i.e., IL-10, IL-1 receptor antagonist (IL-1 RA), indoleamine 2,3-dioxygenase, and soluble TNF receptor type II (sTNF RII). Under miRTar prediction, miR-671-5p was identified as a critical microRNA in regulation of multiple immune-modulating factors in OFSCs response to macrophages. The baseline level of miR-671-5p was high in OFSCs, and down-regulation of miR-671-5p upon co-culture with activated macrophages was observed. MiR-671-5p inhibitor transfection into OFSCs selectively enhanced the IL-1 RA and sTNF RII expressions. In addition, inhibition of miR-671-5p in OFSCs enhanced the anti-inflammatory ability against LPS-induced ALI. CONCLUSION: The paracrine effect of OFSCs inhibits the pro-inflammatory ability and proliferation of macrophages. The immune-modulation capacity of OFSCs can be triggered by activated macrophages, and down-regulation of miR-671-5p enhances OFSC immuno-modulation ability by up-regulating IL-1 RA and sTNF RII expression.",2014 Aug 13,"['Lien, Gi-Shih', 'Liu, Jen-Fang', 'Chien, Ming-Hsien', 'Hsu, Wei-Tse', 'Chang, Tzu-Hao', 'Ku, Chia-Chi', 'Ji, Andrea Tung-Qian', 'Tan, Peng', 'Hsieh, Ting-Lieh', 'Lee, Liang-Ming', 'Ho, Jennifer H']",Stem Cell Res Ther,,,True
3559efd0d0327a8262022dcdd40d01a6f468cb82,PMC,Persistent viremia by a novel parvovirus in a slow loris (Nycticebus coucang) with diffuse histiocytic sarcoma,http://dx.doi.org/10.3389/fmicb.2014.00655,PMC4249460,25520709,CC BY,"Cancer is one of the leading health concerns for human and animal health. Since the tumorigenesis process is not completely understood and it is known that some viruses can induce carcinogenesis, it is highly important to identify novel oncoviruses and extensively study underlying oncogenic mechanisms. Here, we investigated a case of diffuse histiocytic sarcoma in a 22 year old slow loris (Nycticebus coucang), using a broad spectrum virus discovery technique. A novel parvovirus was discovered and the phylogenetic analysis performed on its fully sequenced genome demonstrated that it represents the first member of a novel genus. The possible causative correlation between this virus and the malignancy was further investigated and 20 serum and 61 organ samples from 25 animals (N. coucang and N. pygmaeus) were screened for the novel virus but only samples collected from the originally infected animal were positive. The virus was present in all tested organs (intestine, liver, spleen, kidneys, and lungs) and in all banked serum samples collected up to 8 years before death. All attempts to identify a latent viral form (integrated or episomal) were unsuccessful and the increase of variation in the viral sequences during the years was consistent with absence of latency. Since it is well known that parvoviruses are dependent on cell division to successfully replicate, we hypothesized that the virus could have benefitted from the constantly dividing cancer cells and may not have been the cause of the histiocytic sarcoma. It is also possible to conjecture that the virus had a role in delaying the tumor progression and this report might bring new exciting opportunities in recognizing viruses to be used in cancer virotherapy.",2014 Dec 1,"['Canuti, Marta', 'Williams, Cathy V.', 'Gadi, Sashi R.', 'Jebbink, Maarten F.', 'Oude Munnink, Bas B.', 'Jazaeri Farsani, Seyed Mohammad', 'Cullen, John M.', 'van der Hoek, Lia']",Front Microbiol,,,True
d8225446cd198441e0d3f3d61387058082932bbf,PMC,"Molecular Detection, Phylogenetic Analysis, and Identification of Transcription Motifs in Feline Leukemia Virus from Naturally Infected Cats in Malaysia",http://dx.doi.org/10.1155/2014/760961,PMC4251355,25506469,CC BY,"A nested PCR assay was used to determine the viral RNA and proviral DNA status of naturally infected cats. Selected samples that were FeLV-positive by PCR were subjected to sequencing, phylogenetic analysis, and motifs search. Of the 39 samples that were positive for FeLV p27 antigen, 87.2% (34/39) were confirmed positive with nested PCR. FeLV proviral DNA was detected in 38 (97.3%) of p27-antigen negative samples. Malaysian FeLV isolates are found to be highly similar with a homology of 91% to 100%. Phylogenetic analysis revealed that Malaysian FeLV isolates divided into two clusters, with a majority (86.2%) sharing similarity with FeLV-K01803 and fewer isolates (13.8%) with FeLV-GM1 strain. Different enhancer motifs including NF-GMa, Krox-20/WT1I-del2, BAF1, AP-2, TBP, TFIIF-beta, TRF, and TFIID are found to occur either in single, duplicate, triplicate, or sets of 5 in different positions within the U3-LTR-gag region. The present result confirms the occurrence of FeLV viral RNA and provirus DNA in naturally infected cats. Malaysian FeLV isolates are highly similar, and a majority of them are closely related to a UK isolate. This study provides the first molecular based information on FeLV in Malaysia. Additionally, different enhancer motifs likely associated with FeLV related pathogenesis have been identified.",2014 Nov 17,"['Bande, Faruku', 'Arshad, Siti Suri', 'Hassan, Latiffah', 'Zakaria, Zunita']",Vet Med Int,,,False
288e7bf5d16ac18731d2f1ee7db6d6ed2a720cc2,PMC,"Molecular Detection, Phylogenetic Analysis, and Identification of Transcription Motifs in Feline Leukemia Virus from Naturally Infected Cats in Malaysia",http://dx.doi.org/10.1155/2014/760961,PMC4251355,25506469,CC BY,"A nested PCR assay was used to determine the viral RNA and proviral DNA status of naturally infected cats. Selected samples that were FeLV-positive by PCR were subjected to sequencing, phylogenetic analysis, and motifs search. Of the 39 samples that were positive for FeLV p27 antigen, 87.2% (34/39) were confirmed positive with nested PCR. FeLV proviral DNA was detected in 38 (97.3%) of p27-antigen negative samples. Malaysian FeLV isolates are found to be highly similar with a homology of 91% to 100%. Phylogenetic analysis revealed that Malaysian FeLV isolates divided into two clusters, with a majority (86.2%) sharing similarity with FeLV-K01803 and fewer isolates (13.8%) with FeLV-GM1 strain. Different enhancer motifs including NF-GMa, Krox-20/WT1I-del2, BAF1, AP-2, TBP, TFIIF-beta, TRF, and TFIID are found to occur either in single, duplicate, triplicate, or sets of 5 in different positions within the U3-LTR-gag region. The present result confirms the occurrence of FeLV viral RNA and provirus DNA in naturally infected cats. Malaysian FeLV isolates are highly similar, and a majority of them are closely related to a UK isolate. This study provides the first molecular based information on FeLV in Malaysia. Additionally, different enhancer motifs likely associated with FeLV related pathogenesis have been identified.",2014 Nov 17,"['Bande, Faruku', 'Arshad, Siti Suri', 'Hassan, Latiffah', 'Zakaria, Zunita']",Vet Med Int,,,True
fb515d76fcd0dcf243425b037693e00c9a1afd34,PMC,Fuse me IFITM can!,http://dx.doi.org/10.1186/s12977-014-0104-x,PMC4251678,25422110,CC BY,,2014 Nov 25,"Fassati, Ariberto",Retrovirology,,,True
4ef4cb3ed4814b1afceebb92b410e53fd5646f4e,PMC,IFITM proteins are incorporated onto HIV-1 virion particles and negatively imprint their infectivity,http://dx.doi.org/10.1186/s12977-014-0103-y,PMC4251951,25422070,CC BY,"BACKGROUND: Interferon induced transmembrane proteins 1, 2 and 3 (IFITMs) belong to a family of highly related antiviral factors that have been shown to interfere with a large spectrum of viruses including Filoviruses, Coronaviruses, Influenza virus, Dengue virus and HIV-1. In all these cases, the reported mechanism of antiviral inhibition indicates that the pool of IFITM proteins present in target cells blocks incoming viral particles in endosomal vesicles where they are subsequently degraded. RESULTS: In this study, we describe an additional mechanism through which IFITMs block HIV-1. In virus-producing cells, IFITMs coalesce with forming virions and are incorporated into viral particles. Expression of IFITMs during virion assembly leads to the production of virion particles of decreased infectivity that are mostly affected during entry in target cells. This mechanism of inhibition is exerted against different retroviruses and does not seem to be dependent on the type of Envelope present on retroviral particles. CONCLUSIONS: The results described here identify a novel mechanism through which IFITMs affect HIV-1 infectivity during the late phases of the viral life cycle. Put in the context of data obtained by other laboratories, these results indicate that IFITMs can target HIV at two distinct moments of its life cycle, in target cells as well as in virus-producing cells. These results raise the possibility that IFITMs could similarly affect distinct steps of the life cycle of a number of other viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-014-0103-y) contains supplementary material, which is available to authorized users.",2014 Nov 25,"['Tartour, Kevin', 'Appourchaux, Romain', 'Gaillard, Julien', 'Nguyen, Xuan-Nhi', 'Durand, Stéphanie', 'Turpin, Jocelyn', 'Beaumont, Elodie', 'Roch, Emmanuelle', 'Berger, Gregory', 'Mahieux, Renaud', 'Brand, Denys', 'Roingeard, Philippe', 'Cimarelli, Andrea']",Retrovirology,,,True
85172df4b29cb30c4e98011ed79e9da2ca63fbd6,PMC,Transcriptional profiling of the spleen in progressive visceral leishmaniasis reveals mixed expression of type 1 and type 2 cytokine-responsive genes,http://dx.doi.org/10.1186/s12865-014-0038-z,PMC4253007,25424735,CC BY,"BACKGROUND: The Syrian golden hamster (Mesocricetus aureus) has been used as a model to study infections caused by a number of human pathogens. Studies of immunopathogenesis in hamster infection models are challenging because of the limited availability of reagents needed to define cellular and molecular determinants. RESULTS: We sequenced a hamster cDNA library and developed a first-generation custom cDNA microarray that included 5131 unique cDNAs enriched for immune response genes. We used this microarray to interrogate the hamster spleen response to Leishmania donovani, an intracellular protozoan that causes visceral leishmaniasis. The hamster model of visceral leishmaniasis is of particular interest because it recapitulates clinical and immunopathological features of human disease, including cachexia, massive splenomegaly, pancytopenia, immunosuppression, and ultimately death. In the microarray a differentially expressed transcript was identified as having at least a 2-fold change in expression between uninfected and infected groups and a False Discovery Rate of <5%. Following a relatively silent early phase of infection (at 7 and 14 days post-infection only 8 and 24 genes, respectively, were differentially expressed), there was dramatic upregulation of inflammatory and immune-related genes in the spleen (708 differentially expressed genes were evident at 28 days post-infection). The differentially expressed transcripts included genes involved in inflammation, immunity, and immune cell trafficking. Of particular interest there was concomitant upregulation of the IFN-γ and interleukin (IL)-4 signaling pathways, with increased expression of a battery of IFN-γ- and IL-4-responsive genes. The latter included genes characteristic of alternatively activated macrophages. CONCLUSIONS: Transcriptional profiling was accomplished in the Syrian golden hamster, for which a fully annotated genome is not available. In the hamster model of visceral leishmaniasis, a robust and functional IFN-γ response did not restrain parasite load and progression of disease. This supports the accumulating evidence that macrophages are ineffectively activated to kill the parasite. The concomitant expression of IL-4/IL-13 and their downstream target genes, some of which were characteristic of alternative macrophage activation, are likely to contribute to this. Further dissection of mechanisms that lead to polarization of macrophages toward a permissive state is needed to fully understand the pathogenesis of visceral leishmaniasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12865-014-0038-z) contains supplementary material, which is available to authorized users.",2014 Nov 26,"['Espitia, Claudia M', 'Saldarriaga, Omar A', 'Travi, Bruno L', 'Osorio, E Yaneth', 'Hernandez, Alvaro', 'Band, Mark', 'Patel, Mandakini J', 'Medina, Audrie A', 'Cappello, Michael', 'Pekosz, Andrew', 'Melby, Peter C']",BMC Immunol,,,True
70419bf8c8f69f99d3127967e958ead655296b3e,PMC,Cryptosporidiosis caused by Cryptosporidium parvum subtype IIdA15G1 at a dairy farm in Northwestern China,http://dx.doi.org/10.1186/s13071-014-0529-z,PMC4254006,25430474,CC BY,"BACKGROUND: Cryptosporidium spp. are zoonotic parasites responsible for diarrhoeal diseases in animals and humans worldwide. Cattle are the most common mammalian species in which Cryptosporidium is detected, with pre-weaned calves considered to be reservoirs for zoonotic C. parvum. In October 2013, severe diarrhoea was observed in 396 pre-weaned calves at a farm in the Ningxia Autonomous Region of Northwestern China. 356 of the infected calves died despite antibiotic therapy. FINDINGS: 252 faecal samples were collected from the investigated farm. The identity of Cryptosporidium species was determined by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) analysis, and by DNA sequence analysis of the small subunit (SSU) rRNA gene. C. parvum was subtyped using sequence analysis of the 60 kDa glycoprotein (gp60) gene. The highest infection rate of 83.3% (40/48) was seen in 2–3-week-old calves with diarrhoea, corresponding to the age at which animals died. Three Cryptosporidium species were identified, including C. parvum (n = 51), C. bovis (n = 1), and C. ryanae (n = 1). All C. parvum isolates were further identified as subtype IIdA15G1. CONCLUSIONS: Cryptosporidium parvum was likely to be most responsible for diarrhoea and death. This is the first report of a cryptosporidiosis outbreak caused by C. parvum IIdA15G1 in Chinese dairy cattle.",2014 Nov 27,"['Cui, Zhaohui', 'Wang, Rongjun', 'Huang, Jianying', 'Wang, Haiyan', 'Zhao, Jinfeng', 'Luo, Nannan', 'Li, Junqiang', 'Zhang, Zhenjie', 'Zhang, Longxian']",Parasit Vectors,,,True
9138f2909ac88cdf8463d08e4559197edc2c60ee,PMC,Identification of a novel nidovirus in an outbreak of fatal respiratory disease in ball pythons (Python regius),http://dx.doi.org/10.1186/1743-422X-11-144,PMC4254391,25106433,CC BY,"BACKGROUND: Respiratory infections are important causes of morbidity and mortality in reptiles; however, the causative agents are only infrequently identified. FINDINGS: Pneumonia, tracheitis and esophagitis were reported in a collection of ball pythons (Python regius). Eight of 12 snakes had evidence of bacterial pneumonia. High-throughput sequencing of total extracted nucleic acids from lung, esophagus and spleen revealed a novel nidovirus. PCR indicated the presence of viral RNA in lung, trachea, esophagus, liver, and spleen. In situ hybridization confirmed the presence of intracellular, intracytoplasmic viral nucleic acids in the lungs of infected snakes. Phylogenetic analysis based on a 1,136 amino acid segment of the polyprotein suggests that this virus may represent a new species in the subfamily Torovirinae. CONCLUSIONS: This report of a novel nidovirus in ball pythons may provide insight into the pathogenesis of respiratory disease in this species and enhances our knowledge of the diversity of nidoviruses.",2014 Aug 8,"['Uccellini, Lorenzo', 'Ossiboff, Robert J', 'de Matos, Ricardo EC', 'Morrisey, James K', 'Petrosov, Alexandra', 'Navarrete-Macias, Isamara', 'Jain, Komal', 'Hicks, Allison L', 'Buckles, Elizabeth L', 'Tokarz, Rafal', 'McAloose, Denise', 'Lipkin, Walter Ian']",Virol J,,,True
e488697a5a07d8a7077f4dae04f386ff038fba5b,PMC,Elevated dietary zinc oxide levels do not have a substantial effect on porcine reproductive and respiratory syndrome virus (PPRSV) vaccination and infection,http://dx.doi.org/10.1186/1743-422X-11-140,PMC4254400,25103309,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important infectious agents for the swine industry worldwide. Zinc (Zn) salts, which are widely used as a dietary supplement in swine nutrition, have shown antiviral effects in vitro as well as in vivo. The purpose of this study was to determine the influence of dietary zinc oxide supplementation on vaccination and challenge infection with PRRSV. FINDINGS: The clinical course of PRRS and the success of vaccination with an experimental inactivated vaccine were compared between animals receiving a conventional diet (50 ppm Zn, control group) and diets supplemented with Zn oxide (ZnO) at final Zn concentrations of 150 or 2,500 ppm. Pigs receiving higher dietary Zn levels showed a tendency towards higher neutralizing antibody levels after infection, while dietary Zn levels did not substantially influence the number of antiviral IFN-gamma secreting cells (IFN-gamma-SC) or percentages of blood immune cell subsets after infection. Finally, feeding higher dietary Zn levels reduced neither clinical symptoms nor viral loads. CONCLUSIONS: Our results suggest that higher levels of dietary ZnO do not have the potential to stimulate or modulate systemic immune responses after vaccination and heterologous PRRSV infection to an extent that could improve the clinical and virological outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1743-422X-11-140) contains supplementary material, which is available to authorized users.",2014 Aug 8,"['Chai, Weidong', 'Wang, Zhenya', 'Janczyk, Pawel', 'Twardziok, Sven', 'Blohm, Ulrike', 'Osterrieder, Nikolaus', 'Burwinkel, Michael']",Virol J,,,True
c458f17d49c0b39b4ac6fece7f994fd9f6ede076,PMC,Identification and characterization of unrecognized viruses in stool samples of non-polio acute flaccid paralysis children by simplified VIDISCA,http://dx.doi.org/10.1186/1743-422X-11-146,PMC4254409,25112200,CC BY,"BACKGROUND: The use of sequence independent methods combined with next generation sequencing for identification purposes in clinical samples appears promising and exciting results have been achieved to understand unexplained infections. One sequence independent method, Virus Discovery based on cDNA Amplified Fragment Length Polymorphism (VIDISCA) is capable of identifying viruses that would have remained unidentified in standard diagnostics or cell cultures. METHODS: VIDISCA is normally combined with next generation sequencing, however, we set up a simplified VIDISCA which can be used in case next generation sequencing is not possible. Stool samples of 10 patients with unexplained acute flaccid paralysis showing cytopathic effect in rhabdomyosarcoma cells and/or mouse cells were used to test the efficiency of this method. To further characterize the viruses, VIDISCA-positive samples were amplified and sequenced with gene specific primers. RESULTS: Simplified VIDISCA detected seven viruses (70%) and the proportion of eukaryotic viral sequences from each sample ranged from 8.3 to 45.8%. Human enterovirus EV-B97, EV-B100, echovirus-9 and echovirus-21, human parechovirus type-3, human astrovirus probably a type-3/5 recombinant, and tetnovirus-1 were identified. Phylogenetic analysis based on the VP1 region demonstrated that the human enteroviruses are more divergent isolates circulating in the community. CONCLUSION: Our data support that a simplified VIDISCA protocol can efficiently identify unrecognized viruses grown in cell culture with low cost, limited time without need of advanced technical expertise. Also complex data interpretation is avoided thus the method can be used as a powerful diagnostic tool in limited resources. Redesigning the routine diagnostics might lead to additional detection of previously undiagnosed viruses in clinical samples of patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1743-422X-11-146) contains supplementary material, which is available to authorized users.",2014 Aug 12,"['Shaukat, Shahzad', 'Angez, Mehar', 'Alam, Muhammad Masroor', 'Jebbink, Maarten F', 'Deijs, Martin', 'Canuti, Marta', 'Sharif, Salmaan', 'de Vries, Michel', 'Khurshid, Adnan', 'Mahmood, Tariq', 'van der Hoek, Lia', 'Zaidi, Syed Sohail Zahoor']",Virol J,,,True
7cb5fb2bfbc900ec54fa097f45d3e43cd160bd3d,PMC,"Full-Length Genome Sequence of a Variant Porcine Epidemic Diarrhea Virus Strain, CH/GDZQ/2014, Responsible for a Severe Outbreak of Diarrhea in Piglets in Guangdong, China, 2014",http://dx.doi.org/10.1128/genomeA.01239-14,PMC4256184,25477403,CC BY,"The full-length genome sequence of a variant porcine epidemic diarrhea virus (PEDV) strain, CH/GDZQ/2014, was determined. The isolate was a variant strain with a relatively far relationship with the PEDV strains previously identified in the same area between 2011 and 2012 and was genetically distinct from the CV777-based vaccine strain currently being used in China.",2014 Dec 4,"['Song, Deping', 'Chen, Yanjun', 'Peng, Qi', 'Huang, Dongyan', 'Zhang, Tiansheng', 'Huang, Tao', 'Zhang, Fanfan', 'Zhou, Xinrong', 'Tang, Yuxin']",Genome Announc,,,True
d1fc5729ff932800c93dbe279b36ea3c53375708,PMC,A Novel Psittacine Adenovirus Identified During an Outbreak of Avian Chlamydiosis and Human Psittacosis: Zoonosis Associated with Virus-Bacterium Coinfection in Birds,http://dx.doi.org/10.1371/journal.pntd.0003318,PMC4256287,25474263,CC BY,"Chlamydophila psittaci is found worldwide, but is particularly common among psittacine birds in tropical and subtropical regions. While investigating a human psittacosis outbreak that was associated with avian chlamydiosis in Hong Kong, we identified a novel adenovirus in epidemiologically linked Mealy Parrots, which was not present in healthy birds unrelated to the outbreak or in other animals. The novel adenovirus (tentatively named Psittacine adenovirus HKU1) was most closely related to Duck adenovirus A in the Atadenovirus genus. Sequencing showed that the Psittacine adenovirus HKU1 genome consists of 31,735 nucleotides. Comparative genome analysis showed that the Psittacine adenovirus HKU1 genome contains 23 open reading frames (ORFs) with sequence similarity to known adenoviral genes, and six additional ORFs at the 3′ end of the genome. Similar to Duck adenovirus A, the novel adenovirus lacks LH1, LH2 and LH3, which distinguishes it from other viruses in the Atadenovirus genus. Notably, fiber-2 protein, which is present in Aviadenovirus but not Atadenovirus, is also present in Psittacine adenovirus HKU1. Psittacine adenovirus HKU1 had pairwise amino acid sequence identities of 50.3–54.0% for the DNA polymerase, 64.6–70.7% for the penton protein, and 66.1–74.0% for the hexon protein with other Atadenovirus. The C. psittaci bacterial load was positively correlated with adenovirus viral load in the lung. Immunostaining for fiber protein expression was positive in lung and liver tissue cells of affected parrots, confirming active viral replication. No other viruses were found. This is the first documentation of an adenovirus-C. psittaci co-infection in an avian species that was associated with a human outbreak of psittacosis. Viral-bacterial co-infection often increases disease severity in both humans and animals. The role of viral-bacterial co-infection in animal-to-human transmission of infectious agents has not received sufficient attention and should be emphasized in the investigation of disease outbreaks in human and animals.",2014 Dec 4,"['To, Kelvin K. W.', 'Tse, Herman', 'Chan, Wan-Mui', 'Choi, Garnet K. Y.', 'Zhang, Anna J. X.', 'Sridhar, Siddharth', 'Wong, Sally C. Y.', 'Chan, Jasper F. W.', 'Chan, Andy S. F.', 'Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Lo, Janice Y. C.', 'Chan, Kwok-Hung', 'Cheng, Vincent C. C.', 'Yuen, Kwok-Yung']",PLoS Negl Trop Dis,,,True
450b87fb527fca46dfc933e35d4de041bf170bd9,PMC,"Emergence of MERS-CoV in the Middle East: Origins, Transmission, Treatment, and Perspectives",http://dx.doi.org/10.1371/journal.ppat.1004457,PMC4256428,25474536,CC BY,,2014 Dec 4,"['Sharif-Yakan, Ahmad', 'Kanj, Souha S.']",PLoS Pathog,,,True
80b0747661793f45be4bc78da3223c63354331ca,PMC,Rapid Identification of Black Grain Eumycetoma Causative Agents Using Rolling Circle Amplification,http://dx.doi.org/10.1371/journal.pntd.0003368,PMC4256478,25474355,CC BY,"Accurate identification of mycetoma causative agent is a priority for treatment. However, current identification tools are far from being satisfactory for both reliable diagnosis and epidemiological investigations. A rapid, simple, and highly efficient molecular based method for identification of agents of black grain eumycetoma is introduced, aiming to improve diagnostic in endemic areas. Rolling Circle Amplification (RCA) uses species-specific padlock probes and isothermal DNA amplification. The tests were based on ITS sequences and developed for Falciformispora senegalensis, F. tompkinsii, Madurella fahalii, M. mycetomatis, M. pseudomycetomatis, M. tropicana, Medicopsis romeroi, and Trematosphaeria grisea. With the isothermal RCA assay, 62 isolates were successfully identified with 100% specificity and no cross reactivity or false results. The main advantage of this technique is the low-cost, high specificity, and simplicity. In addition, it is highly reproducible and can be performed within a single day.",2014 Dec 4,"['Ahmed, Sarah A.', 'van den Ende, Bert H. G. Gerrits', 'Fahal, Ahmed H.', 'van de Sande, Wendy W. J.', 'de Hoog, G. S.']",PLoS Negl Trop Dis,,,True
04605d35cd46d435e96dc82778096c879327a5dc,PMC,Rapid Identification of Black Grain Eumycetoma Causative Agents Using Rolling Circle Amplification,http://dx.doi.org/10.1371/journal.pntd.0003368,PMC4256478,25474355,CC BY,"Accurate identification of mycetoma causative agent is a priority for treatment. However, current identification tools are far from being satisfactory for both reliable diagnosis and epidemiological investigations. A rapid, simple, and highly efficient molecular based method for identification of agents of black grain eumycetoma is introduced, aiming to improve diagnostic in endemic areas. Rolling Circle Amplification (RCA) uses species-specific padlock probes and isothermal DNA amplification. The tests were based on ITS sequences and developed for Falciformispora senegalensis, F. tompkinsii, Madurella fahalii, M. mycetomatis, M. pseudomycetomatis, M. tropicana, Medicopsis romeroi, and Trematosphaeria grisea. With the isothermal RCA assay, 62 isolates were successfully identified with 100% specificity and no cross reactivity or false results. The main advantage of this technique is the low-cost, high specificity, and simplicity. In addition, it is highly reproducible and can be performed within a single day.",2014 Dec 4,"['Ahmed, Sarah A.', 'van den Ende, Bert H. G. Gerrits', 'Fahal, Ahmed H.', 'van de Sande, Wendy W. J.', 'de Hoog, G. S.']",PLoS Negl Trop Dis,,,False
88f1de42ca135e68ca9aa6a10081091fc4443028,PMC,Progress toward universal health coverage in ASEAN,http://dx.doi.org/10.3402/gha.v7.25856,PMC4256544,25476931,CC BY,"BACKGROUND: The Association of Southeast Asian Nations (ASEAN) is characterized by much diversity in terms of geography, society, economic development, and health outcomes. The health systems as well as healthcare structure and provisions vary considerably. Consequently, the progress toward Universal Health Coverage (UHC) in these countries also varies. This paper aims to describe the progress toward UHC in the ASEAN countries and discuss how regional integration could influence UHC. DESIGN: Data reported in this paper were obtained from published literature, reports, and gray literature available in the ASEAN countries. We used both online and manual search methods to gather the information and ‘snowball’ further data. RESULTS: We found that, in general, ASEAN countries have made good progress toward UHC, partly due to relatively sustained political commitments to endorse UHC in these countries. However, all the countries in ASEAN are facing several common barriers to achieving UHC, namely 1) financial constraints, including low levels of overall and government spending on health; 2) supply side constraints, including inadequate numbers and densities of health workers; and 3) the ongoing epidemiological transition at different stages characterized by increasing burdens of non-communicable diseases, persisting infectious diseases, and reemergence of potentially pandemic infectious diseases. The ASEAN Economic Community's (AEC) goal of regional economic integration and a single market by 2015 presents both opportunities and challenges for UHC. Healthcare services have become more available but health and healthcare inequities will likely worsen as better-off citizens of member states might receive more benefits from the liberalization of trade policy in health, either via regional outmigration of health workers or intra-country health worker movement toward private hospitals, which tend to be located in urban areas. For ASEAN countries, UHC should be explicitly considered to mitigate deleterious effects of economic integration. Political commitments to safeguard health budgets and increase health spending will be necessary given liberalization's risks to health equity as well as migration and population aging which will increase demand on health systems. There is potential to organize select health services regionally to improve further efficiency. CONCLUSIONS: We believe that ASEAN has significant potential to become a force for better health in the region. We hope that all ASEAN citizens can enjoy higher health and safety standards, comprehensive social protection, and improved health status. We believe economic and other integration efforts can further these aspirations.",2014 Dec 3,"['Van Minh, Hoang', 'Pocock, Nicola Suyin', 'Chaiyakunapruk, Nathorn', 'Chhorvann, Chhea', 'Duc, Ha Anh', 'Hanvoravongchai, Piya', 'Lim, Jeremy', 'Lucero-Prisno, Don Eliseo', 'Ng, Nawi', 'Phaholyothin, Natalie', 'Phonvisay, Alay', 'Soe, Kyaw Min', 'Sychareun, Vanphanom']",Glob Health Action,,,True
5bcd3c424887a848429ff1027ac2aacf50944fbf,PMC,"Multiple functions of DDX3 RNA helicase in gene regulation, tumorigenesis, and viral infection",http://dx.doi.org/10.3389/fgene.2014.00423,PMC4257086,25538732,CC BY,"The DEAD-box RNA helicase DDX3 is a multifunctional protein involved in all aspects of RNA metabolism, including transcription, splicing, mRNA nuclear export, translation, RNA decay and ribosome biogenesis. In addition, DDX3 is also implicated in cell cycle regulation, apoptosis, Wnt-β-catenin signaling, tumorigenesis, and viral infection. Notably, recent studies suggest that DDX3 is a component of anti-viral innate immune signaling pathways. Indeed, DDX3 contributes to enhance the induction of anti-viral mediators, interferon (IFN) regulatory factor 3 and type I IFN. However, DDX3 seems to be an important target for several viruses, such as human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), hepatitis B virus (HBV), and poxvirus. DDX3 interacts with HIV-1 Rev or HCV Core protein and modulates its function. At least, DDX3 is required for both HIV-1 and HCV replication. Therefore, DDX3 could be a novel therapeutic target for the development of drug against HIV-1 and HCV.",2014 Dec 5,"Ariumi, Yasuo",Front Genet,,,True
be314554a535360c674f8666efdefd43e38e5ccc,PMC,Molecular detection and genotypic characterization of Toxoplasma gondii infection in bats in four provinces of China,http://dx.doi.org/10.1186/s13071-014-0558-7,PMC4258805,25465220,CC BY,"BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite that infects a wide variety of warm-blooded hosts, including humans. Limited information about T. gondii infection in bats is available in China. The objective of the present study was to determine prevalence and genetic characterization of T. gondii infection in bats in Jilin, Liaoning, Jiangxi and Guangdong provinces, China. METHODS: During May 2005 to August 2013, bats were sampled from Jilin, Liaoning, Jiangxi, and Guangdong provinces, China, and liver tissues were collected for the detection of T. gondii by a nested PCR targeting the B1 gene. The positive samples were genotyped at 11 genetic markers (SAG1, 5′-and 3′-SAG2, alternative SAG2, SAG3, BTUB, GRA6, L358, PK1, c22-8, c29-2, and Apico) using multilocus polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A total of 626 bats representing 10 species were examined for T. gondii infection, 38 (6.1%) were tested positive with by PCR, 8 positive DNA samples were completely genotyped, of which 3 samples (2 from Cynopterus sphinx, and 1 from Murina leucogaster) represented ToxoDB#10, and 5 samples (2 from Murina leucogaster, 2 from Myotis chinensis, and 1 from Rhinolophus ferrumequinum) belonged to ToxoDB#9 (http://toxodb.org/toxo/). CONCLUSIONS: The present study revealed an overall T. gondii prevalence of 6.1% in bats from Jilin, Liaoning, Jiangxi and Guangdong provinces in China, and reported two T. gondii genotypes (ToxoDB#9 and #10) having a wide geographical distribution in China. These results provide new genetic information about T. gondii infection in bats, and have implications for better understanding of the genetic diversity of T. gondii in China and elsewhere.",2014 Dec 3,"['Qin, Si-Yuan', 'Cong, Wei', 'Liu, Ye', 'Li, Nan', 'Wang, Ze-Dong', 'Zhang, Fu-Kai', 'Huang, Si-Yang', 'Zhu, Xing-Quan', 'Liu, Quan']",Parasit Vectors,,,True
90b1c08620b3bcc5694e31a241e2be2589003030,PMC,Clostridium difficile carriage in hospitalized cancer patients: a prospective investigation in eastern China,http://dx.doi.org/10.1186/1471-2334-14-523,PMC4261591,25267108,CC BY,"BACKGROUND: Clostridium difficile carriage has been considered as a potential source for the deadly infection, but its role in cancer patients is still unclear. We aimed to identify the clinical and immunological factors that are related to C. difficile carriage in Chinese cancer patients. METHODS: A total of 400 stool samples were collected from cancer patients who received chemotherapy in three hospitals of eastern China. Bacterial genomic DNA was extracted and two toxin genes (tcdA and tcdB) were detected. PCR ribotyping was performed using capillary gel electrophoresis. Concentrations of prostaglandin E2 (PGE2), transforming growth factor beta (TGF-β) and interleukin-10 (IL-10) were measured using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Eighty-two (20.5%) samples were confirmed to be C. difficile-positive and positive for tpi, tcdA, and tcdB genes. The C. difficile-positive rates in patients with diarrhea and no diarrhea were 35% and 19.7%, respectively (p = 0.09). Patients who were younger than 50 years old and were hospitalized for at least 10 days had a C. difficile-positive rate as high as 35%. In contrast, patients who were older than 50 years old and were hospitalized for less than 10 days had a C. difficile-positive rate of only 12.7% (p = 0.0009). No association was found between C. difficile carriage and chemotherapy regimen, antibiotic drug use, or immunosuppressive mediators, such as prostaglandin E2 (PGE2), transforming growth factor beta (TGF-β), or interleukin-10 (IL-10). Twelve ribotypes of C. difficile were identified, but none of them belonged to ribotype 027. CONCLUSIONS: We conclude that younger patients and those with longer hospitalization stays may be more prone to C. difficile carriage. Studies of larger populations are warranted to clarify the exact role of C. difficile carriage in hospitalized cancer patients in China. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-523) contains supplementary material, which is available to authorized users.",2014 Sep 29,"['Fang, Wei-Jia', 'Jing, Da-Zhi', 'Luo, Yun', 'Fu, Cai-Yun', 'Zhao, Peng', 'Qian, Jiong', 'Tian, Bing-Ru', 'Chen, Xiao-Gang', 'Zheng, Yu-Long', 'Zheng, Yi', 'Deng, Jing', 'Zou, Wei-Hua', 'Feng, Xue-Ren', 'Liu, Fan-Long', 'Mou, Xiao-Zhou', 'Zheng, Shu-Sen']",BMC Infect Dis,,,True
20c5f4025a94ca3a48d6d8a23a9db2ebc8b5ec03,PMC,Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are predictors of bronchiolitis severity,http://dx.doi.org/10.1111/irv.12276,PMC4262276,25132512,CC BY,"BACKGROUND: Bronchiolitis is the leading cause of hospitalization in infants. Biomarkers of disease severity might help in clinical management. OBJECTIVE: To determine the clinical predictiveness of NW-LDH, NW-caspase 3/7, and NW-LDH/NW-caspase 3/7 ratio in bronchiolitis. METHODS: Previously healthy children less than 24 months of age with bronchiolitis were recruited from the Texas Children's emergency room and intensive care unit from October 2010 to April 2011. Demographic, clinical information, and NW samples were obtained at enrollment. NW samples were analyzed for respiratory viruses, caspase 3/7, and LDH. RESULTS: A viral pathogen was detected in 91·6% of 131 children, with the most common being respiratory syncytial virus and human rhinovirus. A single infection was found in 61·8% of subjects and co-infection in 29·8%. Children admitted to ICU had significantly higher NW-LDH than children sent home from the ER or admitted to the general floor (P = 0·02). Children infected with RSV had the highest NW-LDH concentration (P = 0·03) compared with other viral infections. NW-LDH and NW-caspase were significantly correlated (r = 0·77, P < 0·0001). The univariate models showed NW-LDH and NW-LDH/NW- caspase 3/7 ratio were directly associated with hospitalization. Mutivariate regression analyses suggested a complex interaction between the biomarkers, demographics, and disposition. CONCLUSIONS: NW-LDH, NW-caspase 3/7 and NW-LDH/NW-caspase 3/7 ratio and their interactions with demographic factors are predictive of bronchiolitis severity and can help distinguish children requiring ICU-level care from those admitted to the general floor, or discharged home from the emergency center.",2014 Nov 12,"['Mehta, Reena', 'Scheffler, Margaret', 'Tapia, Lorena', 'Aideyan, Letisha', 'Patel, Kirtida D', 'Jewell, Alan M', 'Avadhanula, Vasanthi', 'Mei, Minghua', 'Garofalo, Roberto P', 'Piedra, Pedro A']",Influenza Other Respir Viruses,,,True
d100ca657bd37c9878a08f7fcc3a9b8ad2d1830f,PMC,Population-based hospitalization incidence of respiratory viruses in community-acquired pneumonia in children younger than 5 years of age,http://dx.doi.org/10.1111/irv.12277,PMC4262277,25185835,CC BY,,2014 Nov 3,"['Chiu, Susan S', 'Ho, Pak-Leung', 'Peiris, Malik J S', 'Chan, Kwok Hung', 'Chan, Eunice L Y']",Influenza Other Respir Viruses,,,True
d494b68c054d6058bce92529a6d9ef3f7302094f,PMC,Insights into potential pathogenesis mechanisms associated with Campylobacter jejuni-induced abortion in ewes,http://dx.doi.org/10.1186/s12917-014-0274-8,PMC4262353,25420712,CC BY,"BACKGROUND: Campylobacter jejuni is commonly found in the gastrointestinal tract of many food-animals including sheep without causing visible clinical symptoms of disease. However, C. jejuni has been implicated in ovine abortion cases worldwide. Specifically, in the USA, the C. jejuni sheep abortion (SA) clone has been increasingly associated with sheep abortion. In vivo studies in sheep (the natural host) are needed to better characterize the virulence potential and pathogenesis of this clone. RESULTS: Pregnant ewes intravenously (IV) or orally inoculated with ovine or bovine abortion-associated C. jejuni SA clones exhibited partial or complete uterine prolapse with retained placenta, and abortion or stillbirth, whereas delivery of healthy lambs occurred in pregnant ewes inoculated with C. jejuni 81–176 or in the uninfected group. In sheep inoculated with the SA clone, histopathological lesions including suppurative necrotizing placentitis and/or endometritis coincided with: 1) increased apoptotic death of trophoblasts, 2) increased expression of the host genes (e.g. genes encoding interleukin IL-6 and IL-15) related to cellular necrosis and pro-inflammatory responses in uterus, and 3) decreased expression of the genes encoding GATA binding protein 6, chordin, and insulin-like 3 (INSL3) that account for embryonic development in uterus. Immunohistochemistry revealed localization of bacterial antigens in trophoblasts lining the chorioallantoic membrane of ewes inoculated with the C. jejuni SA clone. CONCLUSIONS: The results showed that C. jejuni SA clones are capable of causing abortion or stillbirth in experimentally infected sheep. Furthermore, down- or up-regulation of specific genes in the uterus of infected pregnant ewes might implicate host genes in facilitating the disease progression. Since the C. jejuni SA strains share genotypic similarities with clones that have been isolated from human clinical cases of gastroenteritis, these strains might represent a potential public health risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-014-0274-8) contains supplementary material, which is available to authorized users.",2014 Nov 25,"['Sanad, Yasser M', 'Jung, Kwonil', 'Kashoma, Isaac', 'Zhang, Xiaoli', 'Kassem, Issmat I', 'Saif, Yehia M', 'Rajashekara, Gireesh']",BMC Vet Res,,,True
3a8f3c3b8c4be0144795e7dc34472a9a7dd35cc5,PMC,Insights into potential pathogenesis mechanisms associated with Campylobacter jejuni-induced abortion in ewes,http://dx.doi.org/10.1186/s12917-014-0274-8,PMC4262353,25420712,CC BY,"BACKGROUND: Campylobacter jejuni is commonly found in the gastrointestinal tract of many food-animals including sheep without causing visible clinical symptoms of disease. However, C. jejuni has been implicated in ovine abortion cases worldwide. Specifically, in the USA, the C. jejuni sheep abortion (SA) clone has been increasingly associated with sheep abortion. In vivo studies in sheep (the natural host) are needed to better characterize the virulence potential and pathogenesis of this clone. RESULTS: Pregnant ewes intravenously (IV) or orally inoculated with ovine or bovine abortion-associated C. jejuni SA clones exhibited partial or complete uterine prolapse with retained placenta, and abortion or stillbirth, whereas delivery of healthy lambs occurred in pregnant ewes inoculated with C. jejuni 81–176 or in the uninfected group. In sheep inoculated with the SA clone, histopathological lesions including suppurative necrotizing placentitis and/or endometritis coincided with: 1) increased apoptotic death of trophoblasts, 2) increased expression of the host genes (e.g. genes encoding interleukin IL-6 and IL-15) related to cellular necrosis and pro-inflammatory responses in uterus, and 3) decreased expression of the genes encoding GATA binding protein 6, chordin, and insulin-like 3 (INSL3) that account for embryonic development in uterus. Immunohistochemistry revealed localization of bacterial antigens in trophoblasts lining the chorioallantoic membrane of ewes inoculated with the C. jejuni SA clone. CONCLUSIONS: The results showed that C. jejuni SA clones are capable of causing abortion or stillbirth in experimentally infected sheep. Furthermore, down- or up-regulation of specific genes in the uterus of infected pregnant ewes might implicate host genes in facilitating the disease progression. Since the C. jejuni SA strains share genotypic similarities with clones that have been isolated from human clinical cases of gastroenteritis, these strains might represent a potential public health risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-014-0274-8) contains supplementary material, which is available to authorized users.",2014 Nov 25,"['Sanad, Yasser M', 'Jung, Kwonil', 'Kashoma, Isaac', 'Zhang, Xiaoli', 'Kassem, Issmat I', 'Saif, Yehia M', 'Rajashekara, Gireesh']",BMC Vet Res,,,True
f4ff5cb594614337119fc4d7e39600c41119f80b,PMC,Microbial sequencing to improve individual and population health,http://dx.doi.org/10.1186/s13073-014-0103-5,PMC4262389,25505493,CC BY,Recent advances in sequencing technologies are changing the face of infectious disease investigation and control. Personalized anti-infective therapies and surveillance of emergent pathogen outbreaks are just two examples of the potential benefits of merging the fields of genomics and infectious diseases.,2014 Nov 19,"['Peacock, Sharon J', 'Weinstock, George M']",Genome Med,,,True
6525c7e5a16bc1ecd8fcdfda2cc6c82fe89c85c8,PMC,The Genome Landscape of the African Green Monkey Kidney-Derived Vero Cell Line,http://dx.doi.org/10.1093/dnares/dsu029,PMC4263300,25267831,CC BY,"Continuous cell lines that originate from mammalian tissues serve as not only invaluable tools for life sciences, but also important animal cell substrates for the production of various types of biological pharmaceuticals. Vero cells are susceptible to various types of microbes and toxins and have widely contributed to not only microbiology, but also the production of vaccines for human use. We here showed the genome landscape of a Vero cell line, in which 25,877 putative protein-coding genes were identified in the 2.97-Gb genome sequence. A homozygous ∼9-Mb deletion on chromosome 12 caused the loss of the type I interferon gene cluster and cyclin-dependent kinase inhibitor genes in Vero cells. In addition, an ∼59-Mb loss of heterozygosity around this deleted region suggested that the homozygosity of the deletion was established by a large-scale conversion. Moreover, a genomic analysis of Vero cells revealed a female Chlorocebus sabaeus origin and proviral variations of the endogenous simian type D retrovirus. These results revealed the genomic basis for the non-tumourigenic permanent Vero cell lineage susceptible to various pathogens and will be useful for generating new sub-lines and developing new tools in the quality control of Vero cells.",2014 Dec 28,"['Osada, Naoki', 'Kohara, Arihiro', 'Yamaji, Toshiyuki', 'Hirayama, Noriko', 'Kasai, Fumio', 'Sekizuka, Tsuyoshi', 'Kuroda, Makoto', 'Hanada, Kentaro']",DNA Res,,,True
4a87f2bdd6553f6be3c6f415b16e1e152633d46b,PMC,The Genome Landscape of the African Green Monkey Kidney-Derived Vero Cell Line,http://dx.doi.org/10.1093/dnares/dsu029,PMC4263300,25267831,CC BY,"Continuous cell lines that originate from mammalian tissues serve as not only invaluable tools for life sciences, but also important animal cell substrates for the production of various types of biological pharmaceuticals. Vero cells are susceptible to various types of microbes and toxins and have widely contributed to not only microbiology, but also the production of vaccines for human use. We here showed the genome landscape of a Vero cell line, in which 25,877 putative protein-coding genes were identified in the 2.97-Gb genome sequence. A homozygous ∼9-Mb deletion on chromosome 12 caused the loss of the type I interferon gene cluster and cyclin-dependent kinase inhibitor genes in Vero cells. In addition, an ∼59-Mb loss of heterozygosity around this deleted region suggested that the homozygosity of the deletion was established by a large-scale conversion. Moreover, a genomic analysis of Vero cells revealed a female Chlorocebus sabaeus origin and proviral variations of the endogenous simian type D retrovirus. These results revealed the genomic basis for the non-tumourigenic permanent Vero cell lineage susceptible to various pathogens and will be useful for generating new sub-lines and developing new tools in the quality control of Vero cells.",2014 Dec 28,"['Osada, Naoki', 'Kohara, Arihiro', 'Yamaji, Toshiyuki', 'Hirayama, Noriko', 'Kasai, Fumio', 'Sekizuka, Tsuyoshi', 'Kuroda, Makoto', 'Hanada, Kentaro']",DNA Res,,,False
1624c6455f4fb4a8e871403b0e27a217bcdc83b2,PMC,Isothermal Amplification Methods for the Detection of Nucleic Acids in Microfluidic Devices,http://dx.doi.org/10.3390/bios3010018,PMC4263587,25587397,CC BY,"Diagnostic tools for biomolecular detection need to fulfill specific requirements in terms of sensitivity, selectivity and high-throughput in order to widen their applicability and to minimize the cost of the assay. The nucleic acid amplification is a key step in DNA detection assays. It contributes to improving the assay sensitivity by enabling the detection of a limited number of target molecules. The use of microfluidic devices to miniaturize amplification protocols reduces the required sample volume and the analysis times and offers new possibilities for the process automation and integration in one single device. The vast majority of miniaturized systems for nucleic acid analysis exploit the polymerase chain reaction (PCR) amplification method, which requires repeated cycles of three or two temperature-dependent steps during the amplification of the nucleic acid target sequence. In contrast, low temperature isothermal amplification methods have no need for thermal cycling thus requiring simplified microfluidic device features. Here, the use of miniaturized analysis systems using isothermal amplification reactions for the nucleic acid amplification will be discussed.",2012 Dec 27,"['Zanoli, Laura Maria', 'Spoto, Giuseppe']",Biosensors (Basel),,,True
fa5e90f78c7365ea9ad6b8b9cf9b6e43a1ca727c,PMC,"3D QSAR Studies, Pharmacophore Modeling and Virtual Screening on a Series of Steroidal Aromatase Inhibitors",http://dx.doi.org/10.3390/ijms151120927,PMC4264204,25405729,CC BY,"Aromatase inhibitors are the most important targets in treatment of estrogen-dependent cancers. In order to search for potent steroidal aromatase inhibitors (SAIs) with lower side effects and overcome cellular resistance, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of SAIs to build 3D QSAR models. The reliable and predictive CoMFA and CoMSIA models were obtained with statistical results (CoMFA: q(2) = 0.636, r(2)(ncv) = 0.988, r(2)(pred) = 0.658; CoMSIA: q(2) = 0.843, r(2)(ncv) = 0.989, r(2)(pred) = 0.601). This 3D QSAR approach provides significant insights that can be used to develop novel and potent SAIs. In addition, Genetic algorithm with linear assignment of hypermolecular alignment of database (GALAHAD) was used to derive 3D pharmacophore models. The selected pharmacophore model contains two acceptor atoms and four hydrophobic centers, which was used as a 3D query for virtual screening against NCI2000 database. Six hit compounds were obtained and their biological activities were further predicted by the CoMFA and CoMSIA models, which are expected to design potent and novel SAIs.",2014 Nov 14,"['Xie, Huiding', 'Qiu, Kaixiong', 'Xie, Xiaoguang']",Int J Mol Sci,,,True
26ba0cb6190e2a4b476ebf7122a0e439bbe80229,PMC,"MicroRNA miR-320a and miR-140 inhibit mink enteritis virus infection by repression of its receptor, feline transferrin receptor",http://dx.doi.org/10.1186/s12985-014-0210-3,PMC4264318,25465595,CC BY,"Mink enteritis virus (MEV) is one of the most important pathogens in the mink industry. Recent studies have shed light into the role of microRNAs (miRNAs), small noncoding RNAs of length ranging from 18–23 nucleotides (nt), as critical modulators in the host-pathogen interaction networks. We previously showed that miRNA miR-181b can inhibit MEV replication by repression of viral non-structural protein 1 expression. Here, we report that two other miRNAs (miR-320a and miR-140) inhibit MEV entry into feline kidney (F81) cells by downregulating its receptor, transferrin receptor (TfR), by targeting the 3′ untranslated region (UTR) of TfR mRNA, while being themselves upregulated.",2014 Dec 3,"['Sun, Jia-zeng', 'Wang, Jigui', 'Wang, Shuang', 'Yuan, Daoli', 'Li, Zhili', 'Yi, Bao', 'Hou, Qiang', 'Mao, Yaping', 'Liu, Weiquan']",Virol J,,,True
3849786c8c14c11ae4b19b4543672421e5d169fd,PMC,Plant-based vaccines against viruses,http://dx.doi.org/10.1186/s12985-014-0205-0,PMC4264547,25465382,CC BY,"Plant-made or “biofarmed” viral vaccines are some of the earliest products of the technology of plant molecular farming, and remain some of the brightest prospects for the success of this field. Proofs of principle and of efficacy exist for many candidate viral veterinary vaccines; the use of plant-made viral antigens and of monoclonal antibodies for therapy of animal and even human viral disease is also well established. This review explores some of the more prominent recent advances in the biofarming of viral vaccines and therapies, including the recent use of ZMapp for Ebolavirus infection, and explores some possible future applications of the technology.",2014 Dec 3,"Rybicki, Edward P",Virol J,,,True
bbe74d62d65366418b61cb33a4ffe5ffcd3a8fce,PMC,"Characterization of a novel orthoreovirus isolated from fruit bat, China",http://dx.doi.org/10.1186/s12866-014-0293-4,PMC4264558,25433675,CC BY,"BACKGROUND: In recent years novel human respiratory disease agents have been described for Southeast Asia and Australia. The causative pathogens were classified as pteropine orthoreoviruses with a strong phylogenetic relationship to orthoreoviruses of bat origin. RESULTS: In this report, we isolated a novel Melaka-like reovirus (named “Cangyuan virus”) from intestinal content samples of one fruit bat residing in China’s Yunnan province. Phylogenetic analysis of the whole Cangyuan virus genome sequences of segments L, M and S demonstrated the genetic diversity of the Cangyuan virus. In contrast to the L and M segments, the phylogenetic trees for the S segments of Cangyuan virus demonstrated a greater degree of heterogeneity. CONCLUSIONS: Phylogenetic analysis indicated that the Cangyuan virus was a novel orthoreovirus and substantially different from currently known members of Pteropine orthoreovirus (PRV) species group. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-014-0293-4) contains supplementary material, which is available to authorized users.",2014 Nov 30,"['Hu, Tingsong', 'Qiu, Wei', 'He, Biao', 'Zhang, Yan', 'Yu, Jing', 'Liang, Xiu', 'Zhang, Wendong', 'Chen, Gang', 'Zhang, Yingguo', 'Wang, Yiyin', 'Zheng, Ying', 'Feng, Ziliang', 'Hu, Yonghe', 'Zhou, Weiguo', 'Tu, Changchun', 'Fan, Quanshui', 'Zhang, Fuqiang']",BMC Microbiol,,,True
d2d1d6227304c56323303dc51509bf3217925dcb,PMC,Lipid interactions during virus entry and infection,http://dx.doi.org/10.1111/cmi.12340,PMC4265854,25131438,CC BY,"For entry and infection viruses have developed numerous strategies to subjugate indispensable cellular factors and functions. Host cell lipids and cellular lipid synthesis machinery are no exception. Not only do viruses exploit existing lipid signalling and modifications for virus entry and trafficking, they also reprogram lipid synthesis, metabolism, and compartmentalization for assembly and egress. Here we review these various concepts and highlight recent progress in understanding viral interactions with host cell lipids during entry and assembly.",2014 Sep 11,"['Mazzon, Michela', 'Mercer, Jason']",Cell Microbiol,,,True
fee63d10e8db56b72c9385149a4e57afa8500981,PMC,Polymorphisms in the feline TNFA and CD209 genes are associated with the outcome of feline coronavirus infection,http://dx.doi.org/10.1186/s13567-014-0123-6,PMC4267428,25512064,CC BY,"Feline infectious peritonitis (FIP), caused by feline coronavirus (FCoV) infection, is a highly lethal disease without effective therapy and prevention. With an immune-mediated disease entity, host genetic variant was suggested to influence the occurrence of FIP. This study aimed at evaluating cytokine-associated single nucleotide polymorphisms (SNPs), i.e., tumor necrosis factor alpha (TNF-α), receptor-associated SNPs, i.e., C-type lectin DC-SIGN (CD209), and the five FIP-associated SNPs identified from Birman cats of USA and Denmark origins and their associations with the outcome of FCoV infection in 71 FIP cats and 93 FCoV infected non-FIP cats in a genetically more diverse cat populations. A promoter variant, fTNFA - 421 T, was found to be a disease-resistance allele. One SNP was identified in the extracellular domain (ECD) of fCD209 at position +1900, a G to A substitution, and the A allele was associated with FIP susceptibility. Three SNPs located in the introns of fCD209, at positions +2276, +2392, and +2713, were identified to be associated with the outcome of FCoV infection, with statistical relevance. In contrast, among the five Birman FIP cat-associated SNPs, no genotype or allele showed significant differences between our FIP and non-FIP groups. As disease resistance is multifactorial and several other host genes could involve in the development of FIP, the five genetic traits identified in this study should facilitate in the future breeding of the disease-resistant animal to reduce the occurrence of cats succumbing to FIP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-014-0123-6) contains supplementary material, which is available to authorized users.",2014 Dec 16,"['Wang, Ying-Ting', 'Hsieh, Li-En', 'Dai, Yu-Rou', 'Chueh, Ling-Ling']",Vet Res,,,True
d9367d8e090900c57b11a99848144bd83dcb80bb,PMC,ApoD Mediates Binding of HDL to LDL and to Growing T24 Carcinoma,http://dx.doi.org/10.1371/journal.pone.0115180,PMC4267786,25513803,CC BY,"Apolipoprotein (Apo) D is an important protein produced in many parts of the body. It is necessary for the development and repair of the brain and protection from oxidative stress. The purpose of this study was to investigate the extent to which apoD interacts with lipoproteins in human plasma. By using detergent-free ELISA, we show that immobilized monoclonal antibodies against apoD very efficiently bind to low density lipoprotein (LDL) from plasma; this binding is as equally efficient as binding to an anti-apoB monoclonal antibody. Adding detergent to the plasma inhibited the binding, suggesting that the binding is dependent on the presence of intact lipoprotein particles. Reversing the system by using immobilized anti-apoB revealed that the affinity of apoD for LDL is rather low, suggesting that multiple bindings are needed for a durable connection. Biosensor experiments using purified lipoproteins also showed that purified apoD and high density lipoprotein 3 (HDL3), a lipoprotein fraction rich in apoD, were both able to bind LDL very efficiently, indicating that the HDL3-LDL interaction may be a physiological consequence of the affinity of apoD for LDL. Furthermore, we found that apoD increases the binding of HDL to actively growing T24 bladder carcinoma cells but not to quiescent, contact-inhibited, confluent T24 cells. This result is especially intriguing given that the T24 supernatant only contained detectable levels of apoD after growth inhibition, raising the possibility that alternating the expression of apoD and a putative apoD-receptor could give direction to the flow of lipids. In the current paper, we conclude that apoD mediates binding of HDL to LDL and to growing T24 carcinomas, thereby highlighting the importance of apoD in lipid metabolism.",2014 Dec 16,"['Braesch-Andersen, Sten', 'Beckman, Lena', 'Paulie, Staffan', 'Kumagai-Braesch, Makiko']",PLoS One,,,True
d51ce457ef5e113a0dfbd40dfb57e438e7d458ef,PMC,Proteomics informed by transcriptomics reveals Hendra virus sensitizes bat cells to TRAIL-mediated apoptosis,http://dx.doi.org/10.1186/s13059-014-0532-x,PMC4269970,25398248,CC BY,"BACKGROUND: Bats are a major reservoir of emerging infectious viruses. Many of these viruses are highly pathogenic to humans however bats remain asymptomatic. The mechanism by which bats control viral replication is unknown. Here we utilize an integrated approach of proteomics informed by transcriptomics to compare the response of immortalized bat and human cells following infection with the highly pathogenic bat-borne Hendra virus (HeV). RESULTS: The host response between the cell lines was significantly different at both the mRNA and protein levels. Human cells demonstrated minimal response eight hours post infection, followed by a global suppression of mRNA and protein abundance. Bat cells demonstrated a robust immune response eight hours post infection, which led to the up-regulation of apoptosis pathways, mediated through the tumor necrosis factor-related apoptosis inducing ligand (TRAIL). HeV sensitized bat cells to TRAIL-mediated apoptosis, by up-regulating death receptor transcripts. At 48 and 72 hours post infection, bat cells demonstrated a significant increase in apoptotic cell death. CONCLUSIONS: This is the first study to comprehensively compare the response of bat and human cells to a highly pathogenic zoonotic virus. An early induction of innate immune processes followed by apoptosis of virally infected bat cells highlights the possible involvement of programmed cell death in the host response. Our study shows for the first time a side-by-side high-throughput analysis of a dangerous zoonotic virus in cell lines derived from humans and the natural bat host. This enables a way to search for divergent mechanisms at a molecular level that may influence host pathogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0532-x) contains supplementary material, which is available to authorized users.",2014 Nov 15,"['Wynne, James W', 'Shiell, Brian J', 'Marsh, Glenn A', 'Boyd, Victoria', 'Harper, Jennifer A', 'Heesom, Kate', 'Monaghan, Paul', 'Zhou, Peng', 'Payne, Jean', 'Klein, Reuben', 'Todd, Shawn', 'Mok, Lawrence', 'Green, Diane', 'Bingham, John', 'Tachedjian, Mary', 'Baker, Michelle L', 'Matthews, David', 'Wang, Lin-Fa']",Genome Biol,,,False
f00106cad50635bb15409ac6039b93b5af031565,PMC,Proteomics informed by transcriptomics reveals Hendra virus sensitizes bat cells to TRAIL-mediated apoptosis,http://dx.doi.org/10.1186/s13059-014-0532-x,PMC4269970,25398248,CC BY,"BACKGROUND: Bats are a major reservoir of emerging infectious viruses. Many of these viruses are highly pathogenic to humans however bats remain asymptomatic. The mechanism by which bats control viral replication is unknown. Here we utilize an integrated approach of proteomics informed by transcriptomics to compare the response of immortalized bat and human cells following infection with the highly pathogenic bat-borne Hendra virus (HeV). RESULTS: The host response between the cell lines was significantly different at both the mRNA and protein levels. Human cells demonstrated minimal response eight hours post infection, followed by a global suppression of mRNA and protein abundance. Bat cells demonstrated a robust immune response eight hours post infection, which led to the up-regulation of apoptosis pathways, mediated through the tumor necrosis factor-related apoptosis inducing ligand (TRAIL). HeV sensitized bat cells to TRAIL-mediated apoptosis, by up-regulating death receptor transcripts. At 48 and 72 hours post infection, bat cells demonstrated a significant increase in apoptotic cell death. CONCLUSIONS: This is the first study to comprehensively compare the response of bat and human cells to a highly pathogenic zoonotic virus. An early induction of innate immune processes followed by apoptosis of virally infected bat cells highlights the possible involvement of programmed cell death in the host response. Our study shows for the first time a side-by-side high-throughput analysis of a dangerous zoonotic virus in cell lines derived from humans and the natural bat host. This enables a way to search for divergent mechanisms at a molecular level that may influence host pathogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0532-x) contains supplementary material, which is available to authorized users.",2014 Nov 15,"['Wynne, James W', 'Shiell, Brian J', 'Marsh, Glenn A', 'Boyd, Victoria', 'Harper, Jennifer A', 'Heesom, Kate', 'Monaghan, Paul', 'Zhou, Peng', 'Payne, Jean', 'Klein, Reuben', 'Todd, Shawn', 'Mok, Lawrence', 'Green, Diane', 'Bingham, John', 'Tachedjian, Mary', 'Baker, Michelle L', 'Matthews, David', 'Wang, Lin-Fa']",Genome Biol,,,True
4600273935786871df51c3644a39d86c3ad2cc8e,PMC,Assembly of viral genomes from metagenomes,http://dx.doi.org/10.3389/fmicb.2014.00714,PMC4270193,25566226,CC BY,"Viral infections remain a serious global health issue. Metagenomic approaches are increasingly used in the detection of novel viral pathogens but also to generate complete genomes of uncultivated viruses. In silico identification of complete viral genomes from sequence data would allow rapid phylogenetic characterization of these new viruses. Often, however, complete viral genomes are not recovered, but rather several distinct contigs derived from a single entity are, some of which have no sequence homology to any known proteins. De novo assembly of single viruses from a metagenome is challenging, not only because of the lack of a reference genome, but also because of intrapopulation variation and uneven or insufficient coverage. Here we explored different assembly algorithms, remote homology searches, genome-specific sequence motifs, k-mer frequency ranking, and coverage profile binning to detect and obtain viral target genomes from metagenomes. All methods were tested on 454-generated sequencing datasets containing three recently described RNA viruses with a relatively large genome which were divergent to previously known viruses from the viral families Rhabdoviridae and Coronaviridae. Depending on specific characteristics of the target virus and the metagenomic community, different assembly and in silico gap closure strategies were successful in obtaining near complete viral genomes.",2014 Dec 18,"['Smits, Saskia L.', 'Bodewes, Rogier', 'Ruiz-Gonzalez, Aritz', 'Baumgärtner, Wolfgang', 'Koopmans, Marion P.', 'Osterhaus, Albert D. M. E.', 'Schürch, Anita C.']",Front Microbiol,,,True
06b3f93a98def37bdbfa4487060cd836fdf1070d,PMC,Platelets and Infection – An Emerging Role of Platelets in Viral Infection,http://dx.doi.org/10.3389/fimmu.2014.00649,PMC4270245,25566260,CC BY,"Platelets are anucleate blood cells that play a crucial role in the maintenance of hemostasis. While platelet activation and elevated platelet counts (thrombocytosis) are associated with increased risk of thrombotic complications, low platelet counts (thrombocytopenia) and several platelet function disorders increase the risk of bleeding. Over the last years, more and more evidence has emerged that platelets and their activation state can also modulate innate and adaptive immune responses and low platelet counts have been identified as a surrogate marker for poor prognosis in septic patients. Viral infections often coincide with platelet activation. Host inflammatory responses result in the release of platelet activating mediators and a pro-oxidative and pro-coagulant environment, which favors platelet activation. However, viruses can also directly interact with platelets and megakaryocytes and modulate their function. Furthermore, platelets can be activated by viral antigen–antibody complexes and in response to some viruses B-lymphocytes also generate anti-platelet antibodies. All these processes contributing to platelet activation result in increased platelet consumption and removal and often lead to thrombocytopenia, which is frequently observed during viral infection. However, virus-induced platelet activation does not only modulate platelet count but also shape immune responses. Platelets and their released products have been reported to directly and indirectly suppress infection and to support virus persistence in response to certain viruses, making platelets a double-edged sword during viral infections. This review aims to summarize the current knowledge on platelet interaction with different types of viruses, the viral impact on platelet activation, and platelet-mediated modulations of innate and adaptive immune responses.",2014 Dec 18,"Assinger, Alice",Front Immunol,,,True
6e30b6ac327ca9f75d9f409d2c0884144569e414,PMC,Genome Sequence of Torovirus Identified from a Pig with Porcine Epidemic Diarrhea Virus from the United States,http://dx.doi.org/10.1128/genomeA.01291-14,PMC4271157,25523767,CC BY,"Porcine torovirus (PToV) strain PToV-NPL/2013 was identified from a pig that tested positive for porcine epidemic diarrhea virus (PEDV). The spike protein-encoding gene from PToV-NPL/2013 had 92% identity with PToV-SH1, suggesting that PToV circulating in the United States is slightly different from the isolates circulating in China. To our knowledge, this is the first report of PToV in the United States.",2014 Dec 18,"['Anbalagan, Srivishnupriya', 'Peterson, Jessica', 'Wassman, Brent', 'Elston, Josh', 'Schwartz, Karen']",Genome Announc,,,True
d71c2fa8fe1c3df75d031c50267993ede529b85c,PMC,The SARS coronavirus papain like protease can inhibit IRF3 at a post activation step that requires deubiquitination activity,http://dx.doi.org/10.1186/s12985-014-0209-9,PMC4272517,25481026,CC BY,"BACKGROUND: The outcome of a viral infection is regulated by complex interactions of viral and host factors. SARS coronavirus (SARS-CoV) engages and regulates several innate immune response pathways during infection. We have previously shown that the SARS-CoV Papain-like Protease (PLpro) inhibits type I interferon (IFN) by inhibiting IRF3 phosphorylation thereby blocking downstream Interferon induction. This finding prompted us to identify other potential mechanisms of inhibition of PLpro on IFN induction. METHODS: We have used plasmids expressing PLpro and IRF3 including an IRF3 mutant that is constitutively active, called IRF3(5D). In these experiments we utilize transfections, chromatin immunoprecipitation, Electro-mobility Shift Assays (EMSA) and protein localization to identify where IRF3 and IRF3(5D) are inhibited by PLpro. RESULTS: Here we show that PLpro also inhibits IRF3 activation at a step after phosphorylation and that this inhibition is dependent on the de-ubiquitination (DUB) activity of PLpro. We found that PLpro is able to block the type I IFN induction of a constitutively active IRF3, but does not inhibit IRF3 dimerization, nuclear localization or DNA binding. However, inhibition of PLpro’s DUB activity by mutagenesis blocked the IRF3 inhibition activity of PLpro, suggesting a role for IRF3 ubiquitination in induction of a type I IFN innate immune response. CONCLUSION: These results demonstrate an additional mechanism that PLpro is able to inhibit IRF3 signaling. These data suggest novel innate immune antagonism activities of PLpro that may contribute to SARS-CoV pathogenesis.",2014 Dec 7,"['Matthews, Krystal', 'Schäfer, Alexandra', 'Pham, Alissa', 'Frieman, Matthew']",Virol J,,,True
374861bab555d907099146fb05867d810fca1ad1,PMC,"Multicenter case–control study protocol of pneumonia etiology in children: Global Approach to Biological Research, Infectious diseases and Epidemics in Low-income countries (GABRIEL network)",http://dx.doi.org/10.1186/s12879-014-0635-8,PMC4272811,25927410,CC BY,"BACKGROUND: Data on the etiologies of pneumonia among children are inadequate, especially in developing countries. The principal objective is to undertake a multicenter incident case–control study of <5-year-old children hospitalized with pneumonia in developing and emerging countries, aiming to identify the causative agents involved in pneumonia while assessing individual and microbial factors associated with the risk of severe pneumonia. METHODS/DESIGN: A multicenter case–control study, based on the GABRIEL network, is ongoing. Ten study sites are located in 9 countries over 3 continents: Brazil, Cambodia, China, Haiti, India, Madagascar, Mali, Mongolia, and Paraguay. At least 1,000 incident cases and 1,000 controls will be enrolled and matched for age and date. Cases are hospitalized children <5 years with radiologically confirmed pneumonia, and the controls are children without any features suggestive of pneumonia. Respiratory specimens are collected from all enrolled subjects to identify 19 viruses and 5 bacteria. Whole blood from pneumonia cases is being tested for 3 major bacteria. S. pneumoniae-positive specimens are serotyped. Urine samples from cases only are tested for detection of antimicrobial activity. The association between procalcitonin, C-reactive protein and pathogens is being evaluated. A discovery platform will enable pathogen identification in undiagnosed samples. DISCUSSION: This multicenter study will provide descriptive results for better understanding of pathogens responsible for pneumonia among children in developing countries. The identification of determinants related to microorganisms associated with pneumonia and its severity should facilitate treatment and prevention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0635-8) contains supplementary material, which is available to authorized users.",2014 Dec 10,"['Picot, Valentina Sanchez', 'Bénet, Thomas', 'Messaoudi, Melina', 'Telles, Jean-Noël', 'Chou, Monidarin', 'Eap, Tekchheng', 'Wang, Jianwei', 'Shen, Kunling', 'Pape, Jean-William', 'Rouzier, Vanessa', 'Awasthi, Shally', 'Pandey, Nitin', 'Bavdekar, Ashish', 'Sanghvi, Sonali', 'Robinson, Annick', 'Contamin, Bénédicte', 'Hoffmann, Jonathan', 'Sylla, Maryam', 'Diallo, Souleymane', 'Nymadawa, Pagbajabyn', 'Dash-Yandag, Budragchaagiin', 'Russomando, Graciela', 'Basualdo, Wilma', 'Siqueira, Marilda M', 'Barreto, Patricia', 'Komurian-Pradel, Florence', 'Vernet, Guy', 'Endtz, Hubert', 'Vanhems, Philippe', 'Paranhos-Baccalà, Gláucia']",BMC Infect Dis,,,True
d018f86bb03f5462f6201a4a2b897df8e5564ca0,PMC,Pulmonary vascular dysfunction in ARDS,http://dx.doi.org/10.1186/s13613-014-0028-6,PMC4273697,25593744,CC BY,"Acute respiratory distress syndrome (ARDS) is characterised by diffuse alveolar damage and is frequently complicated by pulmonary hypertension (PH). Multiple factors may contribute to the development of PH in this setting. In this review, we report the results of a systematic search of the available peer-reviewed literature for papers that measured indices of pulmonary haemodynamics in patients with ARDS and reported on mortality in the period 1977 to 2010. There were marked differences between studies, with some reporting strong associations between elevated pulmonary arterial pressure or elevated pulmonary vascular resistance and mortality, whereas others found no such association. In order to discuss the potential reasons for these discrepancies, we review the physiological concepts underlying the measurement of pulmonary haemodynamics and highlight key differences between the concepts of resistance in the pulmonary and systemic circulations. We consider the factors that influence pulmonary arterial pressure, both in normal lungs and in the presence of ARDS, including the important effects of mechanical ventilation. Pulmonary arterial pressure, pulmonary vascular resistance and transpulmonary gradient (TPG) depend not alone on the intrinsic properties of the pulmonary vascular bed but are also strongly influenced by cardiac output, airway pressures and lung volumes. The great variability in management strategies within and between studies means that no unified analysis of these papers was possible. Uniquely, Bull et al. (Am J Respir Crit Care Med 182:1123–1128, 2010) have recently reported that elevated pulmonary vascular resistance (PVR) and TPG were independently associated with increased mortality in ARDS, in a large trial with protocol-defined management strategies and using lung-protective ventilation. We then considered the existing literature to determine whether the relationship between PVR/TPG and outcome might be causal. Although we could identify potential mechanisms for such a link, the existing evidence does not allow firm conclusions to be drawn. Nonetheless, abnormally elevated PVR/TPG may provide a useful index of disease severity and progression. Further studies are required to understand the role and importance of pulmonary vascular dysfunction in ARDS in the era of lung-protective ventilation.",2014 Aug 22,"['Ryan, Donal', 'Frohlich, Stephen', 'McLoughlin, Paul']",Ann Intensive Care,,,True
a1f20fd6adb16f74b5c4a7c0543c55e80e500e02,PMC,Do we need a replacement medication for influenza with good efficacy?,http://dx.doi.org/10.1186/s40199-014-0084-3,PMC4274729,25523212,CC BY,,2014 Dec 16,"['Arastoo, Mahmoud', 'Khorshid, Hamid Reza Khorram']",Daru,,,True
0f78cf5bc61d9cc158832a1c680d8aca449785dc,PMC,Clinical evaluation of viral acute respiratory tract infections in children presenting to the emergency department of a tertiary referral hospital in the Netherlands,http://dx.doi.org/10.1186/s12887-014-0297-0,PMC4276012,25491885,CC BY,"BACKGROUND: The relative incidence and clinical impact of individual respiratory viruses remains unclear among children presenting to the hospital emergency department with acute respiratory tract infection (ARTI). METHODS: During two winter periods, respiratory virus real-time multiplex PCR results were evaluated from children (< 18 years) presenting to the emergency department of a tertiary referral hospital with ARTI that had been sampled within 48 hours of hospital presentation. In an attempt to identify virus-specific distinguishing clinical features, single virus infections were correlated with presenting signs and symptoms, clinical findings and outcomes using multivariate logistic regression. RESULTS: In total, 274 children with ARTI were evaluated and most were aged < 3 years (236/274, 86%). PCR detected respiratory viruses in 224/274 (81.8%) children and included 162 (59%) single and 62 (23%) mixed virus infections. Respiratory syncytial virus (RSV) and human rhinovirus (HRV) single virus infections were common among children aged < 3 years, but proportional differences compared to older children were only significant for RSV (95% CI 1.3–15). Clinical differentiation between viral ARTIs was not possible due to common shared presenting signs and symptoms and the high frequency of mixed viral infections. We observed virus-associated outcome differences among children aged < 3 years. Oxygen treatment was associated with RSV (OR 3.6) and inversely correlated with FLU (OR 0.05). Treatment with steroids (OR 3.4) or bronchodilators (OR 3.4) was associated with HRV. Severe respiratory complications were associated with HRV (OR 3.5) and inversely correlated with RSV (OR 0.24). CONCLUSIONS: Respiratory viruses are frequently detected in young children presenting to the hospital emergency department with ARTI and require PCR diagnosis since presenting signs and symptoms are not discriminant for a type of virus. RSV and HRV bear a high burden of morbidity in the pediatric clinical setting.",2014 Dec 10,"['Gooskens, Jairo', 'van der Ploeg, Vishnu', 'Sukhai, Ram N', 'Vossen, Ann CTM', 'Claas, Eric CJ', 'Kroes, Aloys CM']",BMC Pediatr,,,True
75957355c6d3c199d42896dfcd2f0f168ef5d348,PMC,Detection of Influenza Virus Infection Using Two PCR Methods,http://dx.doi.org/10.1155/2014/274679,PMC4276355,25574169,CC BY,"Rapid, accurate, and cost-effective methods to identify the cause of respiratory tract infections are needed to maximize clinical benefit. Outpatients with acute respiratory illness were tested for influenza using a singleplex reverse transcriptase polymerase chain reaction (SRT-PCR) method. A multiplex RT-PCR (MRT-PCR) method tested for influenza and 17 other viruses and was compared with SRT-PCR using chi-square tests. Among 935 patients, 335 (36%) tested positive for influenza A and influenza B using SRT-PCR. Using MRT-PCR, 320 (34.2%) tested positive for influenza A and influenza B. This study supports MRT-PCR as a comparable method for detecting influenza among patients seeking outpatient care for acute respiratory illnesses.",2014 Dec 9,"['Zimmerman, Richard K.', 'Rinaldo, Charles R.', 'Nowalk, Mary Patricia', 'Balasubramani, G. K.', 'Thompson, Mark G.', 'Bullotta, Arlene', 'Susick, Michael', 'Wisniewski, Stephen']",Adv Virol,,,True
0b875918f93152038d3a87f24e51abc1fd99a348,PMC,Immunology of Bats and Their Viruses: Challenges and Opportunities,http://dx.doi.org/10.3390/v6124880,PMC4276934,25494448,CC BY,"Bats are reservoir hosts of several high-impact viruses that cause significant human diseases, including Nipah virus, Marburg virus and rabies virus. They also harbor many other viruses that are thought to have caused disease in humans after spillover into intermediate hosts, including SARS and MERS coronaviruses. As is usual with reservoir hosts, these viruses apparently cause little or no pathology in bats. Despite the importance of bats as reservoir hosts of zoonotic and potentially zoonotic agents, virtually nothing is known about the host/virus relationships; principally because few colonies of bats are available for experimental infections, a lack of reagents, methods and expertise for studying bat antiviral responses and immunology, and the difficulty of conducting meaningful field work. These challenges can be addressed, in part, with new technologies that are species-independent that can provide insight into the interactions of bats and viruses, which should clarify how the viruses persist in nature, and what risk factors might facilitate transmission to humans and livestock.",2014 Dec 8,"Schountz, Tony",Viruses,,,True
f6e6534cb423c1823ad38d7d5c0a98c303f2efdb,PMC,Architectural Insight into Inovirus-Associated Vectors (IAVs) and Development of IAV-Based Vaccines Inducing Humoral and Cellular Responses: Implications in HIV-1 Vaccines,http://dx.doi.org/10.3390/v6125047,PMC4276942,25525909,CC BY,"Inovirus-associated vectors (IAVs) are engineered, non-lytic, filamentous bacteriophages that are assembled primarily from thousands of copies of the major coat protein gp8 and just five copies of each of the four minor coat proteins gp3, gp6, gp7 and gp9. Inovirus display studies have shown that the architecture of inoviruses makes all coat proteins of the inoviral particle accessible to the outside. This particular feature of IAVs allows foreign antigenic peptides to be displayed on the outer surface of the virion fused to its coat proteins and for more than two decades has been exploited in many applications including antibody or peptide display libraries, drug design, and vaccine development against infectious and non-infectious diseases. As vaccine carriers, IAVs have been shown to elicit both a cellular and humoral response against various pathogens through the display of antibody epitopes on their coat proteins. Despite their high immunogenicity, the goal of developing an effective vaccine against HIV-1 has not yet materialized. One possible limitation of previous efforts was the use of broadly neutralizing antibodies, which exhibited autoreactivity properties. In the past five years, however, new, more potent broadly neutralizing antibodies that do not exhibit autoreactivity properties have been isolated from HIV-1 infected individuals, suggesting that vaccination strategies aimed at producing such broadly neutralizing antibodies may confer protection against infection. The utilization of these new, broadly neutralizing antibodies in combination with the architectural traits of IAVs have driven the current developments in the design of an inovirus-based vaccine against HIV-1. This article reviews the applications of IAVs in vaccine development, with particular emphasis on the design of inoviral-based vaccines against HIV-1.",2014 Dec 17,"['Hassapis, Kyriakos A.', 'Stylianou, Dora C.', 'Kostrikis, Leondios G.']",Viruses,,,True
06f33aa8d51ad1c6081cd855c8d274d47e1ee74e,PMC,Cytoplasmic Translocation of Polypyrimidine Tract-Binding Protein and Its Binding to Viral RNA during Japanese Encephalitis Virus Infection Inhibits Virus Replication,http://dx.doi.org/10.1371/journal.pone.0114931,PMC4278868,25545659,CC BY,"Japanese encephalitis virus (JEV) has a single-stranded, positive-sense RNA genome containing a single open reading frame flanked by the 5′- and 3′-non-coding regions (NCRs). The virus genome replicates via a negative-sense RNA intermediate. The NCRs and their complementary sequences in the negative-sense RNA are the sites for assembly of the RNA replicase complex thereby regulating the RNA synthesis and virus replication. In this study, we show that the 55-kDa polypyrimidine tract-binding protein (PTB) interacts in vitro with both the 5′-NCR of the positive-sense genomic RNA - 5NCR(+), and its complementary sequence in the negative-sense replication intermediate RNA - 3NCR(-). The interaction of viral RNA with PTB was validated in infected cells by JEV RNA co-immunoprecipitation and JEV RNA-PTB colocalization experiments. Interestingly, we observed phosphorylation-coupled translocation of nuclear PTB to cytoplasmic foci that co-localized with JEV RNA early during JEV infection. Our studies employing the PTB silencing and over-expression in cultured cells established an inhibitory role of PTB in JEV replication. Using RNA-protein binding assay we show that PTB competitively inhibits association of JEV 3NCR(-) RNA with viral RNA-dependent RNA polymerase (NS5 protein), an event required for the synthesis of the plus-sense genomic RNA. cAMP is known to promote the Protein kinase A (PKA)-mediated PTB phosphorylation. We show that cells treated with a cAMP analogue had an enhanced level of phosphorylated PTB in the cytoplasm and a significantly suppressed JEV replication. Data presented here show a novel, cAMP-induced, PTB-mediated, innate host response that could effectively suppress JEV replication in mammalian cells.",2014 Dec 29,"['Bhullar, Deepika', 'Jalodia, Richa', 'Kalia, Manjula', 'Vrati, Sudhanshu']",PLoS One,,,True
8134e0946079f5ef0bbbd7b65ce13657483b8160,PMC,Cullin E3 Ligases and Their Rewiring by Viral Factors,http://dx.doi.org/10.3390/biom4040897,PMC4279162,25314029,CC BY,"The ability of viruses to subvert host pathways is central in disease pathogenesis. Over the past decade, a critical role for the Ubiquitin Proteasome System (UPS) in counteracting host immune factors during viral infection has emerged. This counteraction is commonly achieved by the expression of viral proteins capable of sequestering host ubiquitin E3 ligases and their regulators. In particular, many viruses hijack members of the Cullin-RING E3 Ligase (CRL) family. Viruses interact in many ways with CRLs in order to impact their ligase activity; one key recurring interaction involves re-directing CRL complexes to degrade host targets that are otherwise not degraded within host cells. Removal of host immune factors by this mechanism creates a more amenable cellular environment for viral propagation. To date, a small number of target host factors have been identified, many of which are degraded via a CRL-proteasome pathway. Substantial effort within the field is ongoing to uncover the identities of further host proteins targeted in this fashion and the underlying mechanisms driving their turnover by the UPS. Elucidation of these targets and mechanisms will provide appealing anti-viral therapeutic opportunities. This review is focused on the many methods used by viruses to perturb host CRLs, focusing on substrate sequestration and viral regulation of E3 activity.",2014 Oct 13,"['Mahon, Cathal', 'Krogan, Nevan J.', 'Craik, Charles S.', 'Pick, Elah']",Biomolecules,,,True
1613fd55dff3cde4f7f32fd5b667e548f860b5d3,PMC,Multiplex PCR analysis of clusters of unexplained viral respiratory tract infection in Cambodia,http://dx.doi.org/10.1186/s12985-014-0224-x,PMC4280028,25514971,CC BY,"BACKGROUND: Fevers of unknown origin constitute a substantial disease burden in Southeast Asia. In majority of the cases, the cause of acute febrile illness is not identified. METHODS: We used MassTag PCR, a multiplex assay platform, to test for the presence of 15 viral respiratory agents from 85 patients with unexplained respiratory illness representing six disease clusters that occurred in Cambodia between 2009 and 2012. RESULTS: We detected a virus in 37 (44%) of the cases. Human rhinovirus, the virus detected most frequently, was found in both children and adults. The viruses most frequently detected in children and adults, respectively, were respiratory syncytial virus and enterovirus 68. Sequence analysis indicated that two distinct clades of enterovirus 68 were circulating during this time period. CONCLUSIONS: This is the first report of enterovirus 68 in Cambodia and contributes to the appreciation of this virus as an important respiratory pathogen.",2014 Dec 17,"['Ly, Nary', 'Tokarz, Rafal', 'Mishra, Nischay', 'Sameroff, Stephen', 'Jain, Komal', 'Rachmat, Agus', 'An, Ung Sam', 'Newell, Steven', 'Harrison, Dustin J', 'Lipkin, W Ian']",Virol J,,,True
5d7ef1b6d6d20f3a2d0c1cad4daa1496ef8a195b,PMC,Novel PDE4 Inhibitors Derived from Chinese Medicine Forsythia,http://dx.doi.org/10.1371/journal.pone.0115937,PMC4280171,25549252,CC BY,"Cyclic adenosine monophosphate (cAMP) is a crucial intracellular second messenger molecule that converts extracellular molecules to intracellular signal transduction pathways generating cell- and stimulus-specific effects. Importantly, specific phosphodiesterase (PDE) subtypes control the amplitude and duration of cAMP-induced physiological processes and are therefore a prominent pharmacological target currently used in a variety of fields. Here we tested the extracts from traditional Chinese medicine, Forsythia suspense seeds, which have been used for more than 2000 years to relieve respiratory symptoms. Using structural-functional analysis we found its major lignin, Forsynthin, acted as an immunosuppressant by inhibiting PDE4 in inflammatory and immune cell. Moreover, several novel, selective small molecule derivatives of Forsythin were tested in vitro and in murine models of viral and bacterial pneumonia, sepsis and cytokine-driven systemic inflammation. Thus, pharmacological targeting of PDE4 may be a promising strategy for immune-related disorders characterized by amplified host inflammatory response.",2014 Dec 30,"['Coon, Tiffany A.', 'McKelvey, Alison C.', 'Weathington, Nate M.', 'Birru, Rahel L.', 'Lear, Travis', 'Leikauf, George D.', 'Chen, Bill B.']",PLoS One,,,True
4cbd54dab5ad14f6d8c5ad9fb9bc223cb4431ba3,PMC,Epidemiology of Pathogen-Specific Respiratory Infections among Three US Populations,http://dx.doi.org/10.1371/journal.pone.0114871,PMC4280218,25549089,CC0,"BACKGROUND: Diagnostic tests for respiratory infections can be costly and time-consuming. Improved characterization of specific respiratory pathogens by identifying frequent signs, symptoms and demographic characteristics, along with improving our understanding of coinfection rates and seasonality, may improve treatment and prevention measures. METHODS: Febrile respiratory illness (FRI) and severe acute respiratory infection (SARI) surveillance was conducted from October 2011 through March 2013 among three US populations: civilians near the US–Mexico border, Department of Defense (DoD) beneficiaries, and military recruits. Clinical and demographic questionnaire data and respiratory swabs were collected from participants, tested by PCR for nine different respiratory pathogens and summarized. Age stratified characteristics of civilians positive for influenza and recruits positive for rhinovirus were compared to other and no/unknown pathogen. Seasonality and coinfection rates were also described. RESULTS: A total of 1444 patients met the FRI or SARI case definition and were enrolled in this study. Influenza signs and symptoms varied across age groups of civilians. Recruits with rhinovirus had higher percentages of pneumonia, cough, shortness of breath, congestion, cough, less fever and longer time to seeking care and were more likely to be male compared to those in the no/unknown pathogen group. Coinfections were found in 6% of all FRI/SARI cases tested and were most frequently seen among children and with rhinovirus infections. Clear seasonal trends were identified for influenza, rhinovirus, and respiratory syncytial virus. CONCLUSIONS: The age-stratified clinical characteristics associated with influenza suggest that age-specific case definitions may improve influenza surveillance and identification. Improving identification of rhinoviruses, the most frequent respiratory infection among recruits, may be useful for separating out contagious individuals, especially when larger outbreaks occur. Overall, describing the epidemiology of pathogen specific respiratory diseases can help improve clinical diagnoses, establish baselines of infection, identify outbreaks, and help prioritize the development of new vaccines and treatments.",2014 Dec 30,"['Radin, Jennifer M.', 'Hawksworth, Anthony W.', 'Kammerer, Peter E.', 'Balansay, Melinda', 'Raman, Rema', 'Lindsay, Suzanne P.', 'Brice, Gary T.']",PLoS One,,,True
31a8187c739fcc29ee62764d0c8da44bdc1b4d8d,PMC,Hepatitis C Virus Life Cycle and Lipid Metabolism,http://dx.doi.org/10.3390/biology3040892,PMC4280516,25517881,CC BY,"Hepatitis C Virus (HCV) infects over 150 million people worldwide. In most cases HCV infection becomes chronic, causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. HCV affects the cholesterol homeostasis and at the molecular level, every step of the virus life cycle is intimately connected to lipid metabolism. In this review, we present an update on the lipids and apolipoproteins that are involved in the HCV infectious cycle steps: entry, replication and assembly. Moreover, the result of the assembly process is a lipoviroparticle, which represents a peculiarity of hepatitis C virion. This review illustrates an example of an intricate virus-host interaction governed by lipid metabolism.",2014 Dec 15,"['Popescu, Costin-Ioan', 'Riva, Laura', 'Vlaicu, Ovidiu', 'Farhat, Rayan', 'Rouillé, Yves', 'Dubuisson, Jean']",Biology (Basel),,,True
b8915fde10e62d4b033a9141910e5639590f0bae,PMC,Plant-based solutions for veterinary immunotherapeutics and prophylactics,http://dx.doi.org/10.1186/s13567-014-0117-4,PMC4280687,25559098,CC BY,"An alarming increase in emergence of antibiotic resistance among pathogens worldwide has become a serious threat to our ability to treat infectious diseases according to the World Health Organization. Extensive use of antibiotics by livestock producers promotes the spread of new resistant strains, some of zoonotic concern, which increases food-borne illness in humans and causes significant economic burden on healthcare systems. Furthermore, consumer preferences for meat/poultry/fish produced without the use of antibiotics shape today’s market demand. So, it is viewed as inevitable by the One Health Initiative that humans need to reduce the use of antibiotics and turn to alternative, improved means to control disease: vaccination and prophylactics. Besides the intense research focused on novel therapeutic molecules, both these strategies rely heavily on the availability of cost-effective, efficient and scalable production platforms which will allow large-volume manufacturing for vaccines, antibodies and other biopharmaceuticals. Within this context, plant-based platforms for production of recombinant therapeutic proteins offer significant advantages over conventional expression systems, including lack of animal pathogens, low production costs, fast turnaround and response times and rapid, nearly-unlimited scalability. Also, because dried leaves and seeds can be stored at room temperature for lengthy periods without loss of recombinant proteins, plant expression systems have the potential to offer lucrative benefits from the development of edible vaccines and prophylactics, as these would not require “cold chain” storage and transportation, and could be administered in mass volumes with minimal processing. Several biotechnology companies currently have developed and adopted plant-based platforms for commercial production of recombinant protein therapeutics. In this manuscript, we outline the challenges in the process of livestock immunization as well as the current plant biotechnology developments aimed to address these challenges.",2014 Dec 31,"['Kolotilin, Igor', 'Topp, Ed', 'Cox, Eric', 'Devriendt, Bert', 'Conrad, Udo', 'Joensuu, Jussi', 'Stöger, Eva', 'Warzecha, Heribert', 'McAllister, Tim', 'Potter, Andrew', 'McLean, Michael D', 'Hall, J Christopher', 'Menassa, Rima']",Vet Res,,,True
f7bb1f005066cb4930f83cde4cdc1ff3fe411def,PMC,Overview of the 3rd isirv-Antiviral Group Conference – advances in clinical management,http://dx.doi.org/10.1111/irv.12293,PMC4280814,25399715,CC BY,"This review highlights the main points which emerged from the presentations and discussions at the 3rd isirv-Antiviral Group Conference - advances in clinical management. The conference covered emerging and potentially pandemic influenza viruses and discussed novel/pre-licensure therapeutics and currently approved antivirals and vaccines for the control of influenza. Current data on approved and novel treatments for non-influenza respiratory viruses such as MERS-CoV, respiratory syncytial virus (RSV) and rhinoviruses and the challenges of treating immunocompromised patients with respiratory infections was highlighted.",2015 Jan 15,"['Hurt, Aeron C', 'Hui, David S', 'Hay, Alan', 'Hayden, Frederick G']",Influenza Other Respir Viruses,,,True
4ae32ac7470a95f95ccd2309bfb62a990c1e0e16,PMC,Culturing of respiratory viruses in well-differentiated pseudostratified human airway epithelium as a tool to detect unknown viruses,http://dx.doi.org/10.1111/irv.12297,PMC4280819,25482367,CC BY,"BACKGROUND: Currently, virus discovery is mainly based on molecular techniques. Here, we propose a method that relies on virus culturing combined with state-of-the-art sequencing techniques. The most natural ex vivo culture system was used to enable replication of respiratory viruses. METHOD: Three respiratory clinical samples were tested on well-differentiated pseudostratified tracheobronchial human airway epithelial (HAE) cultures grown at an air–liquid interface, which resemble the airway epithelium. Cells were stained with convalescent serum of the patients to identify infected cells and apical washes were analyzed by VIDISCA-454, a next-generation sequencing virus discovery technique. RESULTS: Infected cells were observed for all three samples. Sequencing subsequently indicated that the cells were infected by either human coronavirus OC43, influenzavirus B, or influenzavirus A. The sequence reads covered a large part of the genome (52%, 82%, and 57%, respectively). CONCLUSION: We present here a new method for virus discovery that requires a virus culture on primary cells and an antibody detection. The virus in the harvest can be used to characterize the viral genome sequence and cell tropism, but also provides progeny virus to initiate experiments to fulfill the Koch's postulates.",2015 Jan 4,"['Jazaeri Farsani, Seyed Mohammad', 'Deijs, Martin', 'Dijkman, Ronald', 'Molenkamp, Richard', 'Jeeninga, Rienk E', 'Ieven, Margareta', 'Goossens, Herman', 'van der Hoek, Lia']",Influenza Other Respir Viruses,,,True
e0d7ff094aad4031bc73a82ae7b4dd6e5f8723c7,PMC,Identification of an Unclassified Paramyxovirus in Coleura afra: A Potential Case of Host Specificity,http://dx.doi.org/10.1371/journal.pone.0115588,PMC4281239,25551455,CC BY,"Bats are known to harbor multiple paramyxoviruses. Despite the creation of two new genera, Aquaparamyxovirus and Ferlavirus, to accommodate this increasing diversity, several recently isolated or characterized viruses remain unclassified beyond the subfamily level. In the present study, among 985 bats belonging to 6 species sampled in the Belinga caves of Gabon, RNA of an unclassified paramyxovirus (Belinga bat virus, BelPV) was discovered in 14 African sheath-tailed bats (Coleura afra), one of which exhibited several hemorrhagic lesions at necropsy, and viral sequence was obtained in two animals. Phylogenetically, BelPV is related to J virus and Beilong virus (BeiPV), two other unclassified paramyxoviruses isolated from rodents. In the diseased BelPV-infected C. afra individual, high viral load was detected in the heart, and the lesions were consistent with those reported in wild rodents and mice experimentally infected by J virus. BelPV was not detected in other tested bat species sharing the same roosting sites and living in very close proximity with C. afra in the two caves sampled, suggesting that this virus may be host-specific for C. afra. The mode of transmission of this paramyxovirus in bat populations remains to be discovered.",2014 Dec 31,"['Maganga, Gael D.', 'Bourgarel, Mathieu', 'Obame Nkoghe, Judicael', ""N'Dilimabaka, Nadine"", 'Drosten, Christian', 'Paupy, Christophe', 'Morand, Serge', 'Drexler, Jan Felix', 'Leroy, Eric M.']",PLoS One,,,True
06e2a26a1925334deaf6621d3b2763924de55b14,PMC,Epidemiologic data and pathogen genome sequences: a powerful synergy for public health,http://dx.doi.org/10.1186/s13059-014-0538-4,PMC4282151,25418119,CC BY,"Epidemiologists aim to inform the design of public health interventions with evidence on the evolution, emergence and spread of infectious diseases. Sequencing of pathogen genomes, together with date, location, clinical manifestation and other relevant data about sample origins, can contribute to describing nearly every aspect of transmission dynamics, including local transmission and global spread. The analyses of these data have implications for all levels of clinical and public health practice, from institutional infection control to policies for surveillance, prevention and treatment. This review highlights the range of epidemiological questions that can be addressed from the combination of genome sequence and traditional ‘line lists’ (tables of epidemiological data where each line includes demographic and clinical features of infected individuals). We identify opportunities for these data to inform interventions that reduce disease incidence and prevalence. By considering current limitations of, and challenges to, interpreting these data, we aim to outline a research agenda to accelerate the genomics-driven transformation in public health microbiology.",2014 Nov 18,"['Grad, Yonatan H', 'Lipsitch, Marc']",Genome Biol,,,True
1f23a8772f471052f70a35fe6921865c014cad71,PMC,"Middle East Respiratory Syndrome Coronavirus Antibody Reactors Among Camels in Dubai, United Arab Emirates, in 2005",http://dx.doi.org/10.1111/tbed.12212,PMC4282458,24456414,CC BY,"We tested, using a low starting dilution, sequential serum samples from dromedary camels, sheep and horses collected in Dubai from February/April to October of 2005 and from dromedary camels for export/import testing between Canada and USA in 2000–2001. Using a standard Middle East respiratory syndrome coronavirus (MERS-CoV) neutralization test, serial sera from three sheep and three horses were all negative while sera from 9 of 11 dromedary camels from Dubai were positive for antibodies supported by similar results in a MERS-CoV recombinant partial spike protein antibody ELISA. The two negative Dubai camels were both dromedary calves and remained negative over the 5 months studied. The six dromedary samples from USA and Canada were negative in both tests. These results support the recent findings that infection with MERS-CoV or a closely related virus is not a new occurrence in camels in the Middle East. Therefore, interactions of MERS-CoV at the human–animal interface may have been ongoing for several, perhaps many, years and by inference, a widespread pandemic may be less likely unless significant evolution of the virus allow accelerated infection and spread potential in the human population.",2014 Apr 24,"['Alexandersen, S', 'Kobinger, G P', 'Soule, G', 'Wernery, U']",Transbound Emerg Dis,,,True
77c758dbd0cc50cb84be51107f421313cba47320,PMC,A Computational Approach for Predicting Role of Human MicroRNAs in MERS-CoV Genome,http://dx.doi.org/10.1155/2014/967946,PMC4283225,25610462,CC BY,"The new epidemic Middle East Respiratory Syndrome (MERS) is caused by a type of human coronavirus called MERS-CoV which has global fatality rate of about 30%. We are investigating potential antiviral therapeutics against MERS-CoV by using host microRNAs (miRNAs) which may downregulate viral gene expression to quell viral replication. We computationally predicted potential 13 cellular miRNAs from 11 potential hairpin sequences of MERS-CoV genome. Our study provided an interesting hypothesis that those miRNAs, that is, hsa-miR-628-5p, hsa-miR-6804-3p, hsa-miR-4289, hsa-miR-208a-3p, hsa-miR-510-3p, hsa-miR-18a-3p, hsa-miR-329-3p, hsa-miR-548ax, hsa-miR-3934-5p, hsa-miR-4474-5p, hsa-miR-7974, hsa-miR-6865-5p, and hsa-miR-342-3p, would be antiviral therapeutics against MERS-CoV infection.",2014 Dec 23,"['Hasan, Md Mahmudul', 'Akter, Rozina', 'Ullah, Md. Shahin', 'Abedin, Md. Jaynul', 'Ullah, G. M. Ahsan', 'Hossain, Md. Zakir']",Adv Bioinformatics,,,True
815b5e537a3e7bdb7d5c7c7cd51181b9b2e245c5,PMC,The Importance of Mouse Models to Define Immunovirologic Determinants of Progressive Multifocal Leukoencephalopathy,http://dx.doi.org/10.3389/fimmu.2014.00646,PMC4283601,25601860,CC BY,"Progressive multifocal leukoencephalopathy (PML) is a severely debilitating and often fatal demyelinating disease of the central nervous system (CNS) in immunosuppressed individuals caused by JC polyomavirus (JCV), a ubiquitous human pathogen. Demyelination results from lytically infected oligodendrocytes, whose clearance is impaired in the setting of depressed JCV-specific T cell-mediated CNS surveillance. Although mutations in the viral capsid and genomic rearrangements in the viral non-coding region appear to set the stage for PML in the immunosuppressed population, mechanisms of demyelination and CNS antiviral immunity are poorly understood in large part due to absence of a tractable animal model that mimics PML neuropathology in humans. Early studies using mouse polyomavirus (MPyV) in T cell-deficient mice demonstrated productive viral replication in the CNS and demyelination; however, these findings were confounded by spinal cord compression by virus-induced vertebral bone tumors. Here, we review current literature regarding animal models of PML, focusing on current trends in antiviral T cell immunity in non-lymphoid organs, including the CNS. Advances in our understanding of polyomavirus lifecycles, viral and host determinants of persistent infection, and T cell-mediated immunity to viral infections in the CNS warrant revisiting polyomavirus CNS infection in the mouse as a bona fide animal model for JCV-PML.",2015 Jan 5,"['Frost, Elizabeth L.', 'Lukacher, Aron E.']",Front Immunol,,,True
45bb84571df3f2e42173366750302b2315783842,PMC,"Genomic analysis of emerging pathogens: methods, application and future trends",http://dx.doi.org/10.1186/s13059-014-0541-9,PMC4283782,25418281,CC BY,"The number of emerging infectious diseases is increasing. Characterizing novel or re-emerging infections is aided by the availability of pathogen genomes. In this review, we evaluate methods that exploit pathogen sequences and the contribution of genomic analysis to understand the epidemiology of recently emerged infectious diseases.",2014 Nov 22,"['Li, Lucy M', 'Grassly, Nicholas C', 'Fraser, Christophe']",Genome Biol,,,True
119585987862e9f02ef0a1748462fb38ecb95b53,PMC,Human infectious diseases in the genomics era: where do we go from here?,http://dx.doi.org/10.1186/s13059-014-0529-5,PMC4283784,25418021,CC BY,"Ripudaman K Bains is the editor of the Genome Biology special issue content on the ‘genomics of infectious diseases’, and introduces the collection in this editorial.",2014 Nov 22,"Bains, Ripudaman K",Genome Biol,,,True
bf0d0a5f74db0e532f85d90285a96f7e70670c55,PMC,Identification of Sumoylated Proteins in the Silkworm Bombyx mori,http://dx.doi.org/10.3390/ijms151222011,PMC4284691,25470021,CC BY,"Small ubiquitin-like modifier (SUMO) modification (SUMOylation) is an important and widely used reversible modification system in eukaryotic cells. It regulates various cell processes, including protein targeting, transcriptional regulation, signal transduction, and cell division. To understand its role in the model lepidoptera insect Bombyx mori, a recombinant baculovirus was constructed to express an enhanced green fluorescent protein (eGFP)-SUMO fusion protein along with ubiquitin carrier protein 9 of Bombyx mori (BmUBC9). SUMOylation substrates from Bombyx mori cells infected with this baculovirus were isolated by immunoprecipitation and identified by LC–ESI-MS/MS. A total of 68 candidate SUMOylated proteins were identified, of which 59 proteins were functionally categorized to gene ontology (GO) terms. Analysis of kyoto encyclopedia of genes and genomes (KEGG) pathways showed that 46 of the identified proteins were involved in 76 pathways that mainly play a role in metabolism, spliceosome and ribosome functions, and in RNA transport. Furthermore, SUMOylation of four candidates (polyubiquitin-C-like isoform X1, 3-hydroxyacyl-CoA dehydrogenase, cyclin-related protein FAM58A-like and GTP-binding nuclear protein Ran) were verified by co-immunoprecipitation in Drosophila schneide 2 cells. In addition, 74% of the identified proteins were predicted to have at least one SUMOylation site. The data presented here shed light on the crucial process of protein sumoylation in Bombyx mori.",2014 Dec 1,"['Tang, Xudong', 'Fu, Xuliang', 'Hao, Bifang', 'Zhu, Feng', 'Xiao, Shengyan', 'Xu, Li', 'Shen, Zhongyuan']",Int J Mol Sci,,,True
b87ddf92d90fd58bbdf08981116cd7841d75d483,PMC,What Macromolecular Crowding Can Do to a Protein,http://dx.doi.org/10.3390/ijms151223090,PMC4284756,25514413,CC BY,"The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”. Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area.",2014 Dec 12,"['Kuznetsova, Irina M.', 'Turoverov, Konstantin K.', 'Uversky, Vladimir N.']",Int J Mol Sci,,,True
883cb0158d0026f5e0b986a72e80266b60dfe98f,PMC,Pathogen Security-Help or Hindrance?,http://dx.doi.org/10.3389/fbioe.2014.00083,PMC4285169,25610829,CC BY,"Events over the past 15 years have resulted in the promulgation of regulations in the United States to enhance biosecurity by restricting the access to pathogens and toxins (i.e., biological select agents and toxins [BSATs]), which pose a severe threat to human being, animal, or plant health or to animal or plant products, to qualified institutions, laboratories, and scientists. These regulations also reduce biosafety concerns by imposing specific requirements on laboratories working with BSATs. Furthermore, they provide a legal framework for prosecuting someone who possesses a BSAT illegally. With the implementation of these regulations has come discussion in the scientific community about the potential of these regulations to affect the cost of doing BSAT research, hamper research and international collaborations, or whether it would stop someone with a microbiological background from isolating many of the select agents from nature.",2015 Jan 6,"Morse, Stephen A.",Front Bioeng Biotechnol,,,True
9b26e1267786a1ec02d8ede9599ec416b7e9f3cf,PMC,Finding and identifying the viral needle in the metagenomic haystack: trends and challenges,http://dx.doi.org/10.3389/fmicb.2014.00739,PMC4285800,25610431,CC BY,"Collectively, viruses have the greatest genetic diversity on Earth, occupy extremely varied niches and are likely able to infect all living organisms. Viral infections are an important issue for human health and cause considerable economic losses when agriculturally important crops or husbandry animals are infected. The advent of metagenomics has provided a precious tool to study viruses by sampling them in natural environments and identifying the genomic composition of a sample. However, reaching a clear recognition and taxonomic assignment of the identified viruses has been hampered by the computational difficulty of these problems. In this perspective paper we examine the trends in current research for the identification of viral sequences in a metagenomic sample, pinpoint the intrinsic computational difficulties for the identification of novel viral sequences within metagenomic samples, and suggest possible avenues to overcome them.",2015 Jan 7,"['Soueidan, Hayssam', 'Schmitt, Louise-Amélie', 'Candresse, Thierry', 'Nikolski, Macha']",Front Microbiol,,,True
9fe4bb195ffbcf6f450478fa94e72e099fb7d335,PMC,Detection of a novel avian influenza A (H7N9) virus in humans by multiplex one-step real-time RT-PCR assay,http://dx.doi.org/10.1186/1471-2334-14-541,PMC4286936,25298249,CC BY,"BACKGROUND: A novel avian influenza A (H7N9) virus emerged in eastern China in February 2013. 413 confirmed human cases, including 157 deaths, have been recorded as of July 31, 2014. METHODS: Clinical specimens, including throat swabs, sputum or tracheal aspirates, etc., were obtained from patients exhibiting influenza-like illness (ILIs), especially from those having pneumonia and a history of occupational exposure to poultry and wild birds. RNA was extracted from these samples and a multiplex one-step real-time RT-PCR assay was developed to specifically detect the influenza A virus (FluA). PCR primers targeted the conserved M and Rnase P (RP) genes, as well as the hemagglutinin and neuraminidase genes of the H7N9 virus. RESULTS: The multiplex assay specifically detected the avian H7N9 virus, and no cross-reaction with other common respiratory pathogens was observed. The detection limit of the assay was approximately 0.05 50% tissue culture infective doses (TCID(50)), or 100 copies per reaction. Positive detection of the H7N9 virus in sputum/tracheal aspirates was higher than in throat swabs during the surveillance of patients with ILIs. Additionally, detection of the matrix (M) and Rnase P genes aided in the determination of the novel avian H7N9 virus and ensured the quality of the clinical samples. CONCLUSIONS: These results demonstrate that the multiplex assay detected the novel avian H7N9 virus with high specificity and sensitivity, which is essential for the early diagnosis and treatment of infected patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-541) contains supplementary material, which is available to authorized users.",2014 Oct 8,"['Fan, Jian', 'Cui, David', 'Lau, Siuying', 'Xie, Guoliang', 'Guo, Xichao', 'Zheng, Shufa', 'Huang, Xiaofeng', 'Yang, Shigui', 'Yang, Xianzhi', 'Huo, Zhaoxia', 'Yu, Fei', 'Lou, Jianzhou', 'Tian, Li', 'Li, Xuefen', 'Dong, Yuejiao', 'Zhu, Qiaoyun', 'Chen, Yu']",BMC Infect Dis,,,True
bc489624c814eedf1d191c84f7ca9efce0c98e1b,PMC,Bi-specific splice-switching PMO oligonucleotides conjugated via a single peptide active in a mouse model of Duchenne muscular dystrophy,http://dx.doi.org/10.1093/nar/gku1256,PMC4288157,25468897,CC BY,"The potential for therapeutic application of splice-switching oligonucleotides (SSOs) to modulate pre-mRNA splicing is increasingly evident in a number of diseases. However, the primary drawback of this approach is poor cell and in vivo oligonucleotide uptake efficacy. Biological activities can be significantly enhanced through the use of synthetically conjugated cationic cell penetrating peptides (CPPs). Studies to date have focused on the delivery of a single SSO conjugated to a CPP, but here we describe the conjugation of two phosphorodiamidate morpholino oligonucleotide (PMO) SSOs to a single CPP for simultaneous delivery and pre-mRNA targeting of two separate genes, exon 23 of the Dmd gene and exon 5 of the Acvr2b gene, in a mouse model of Duchenne muscular dystrophy. Conjugations of PMOs to a single CPP were carried out through an amide bond in one case and through a triazole linkage (‘click chemistry’) in the other. The most active bi-specific CPP–PMOs demonstrated comparable exon skipping levels for both pre-mRNA targets when compared to individual CPP–PMO conjugates both in cell culture and in vivo in the mdx mouse model. Thus, two SSOs with different target sequences conjugated to a single CPP are biologically effective and potentially suitable for future therapeutic exploitation.",2015 Jan 9,"['Shabanpoor, Fazel', 'McClorey, Graham', 'Saleh, Amer F.', 'Järver, Peter', 'Wood, Matthew J.A.', 'Gait, Michael J.']",Nucleic Acids Res,,,True
acadcb58dfdef9e3e9981dde06e2a825c005c9c4,PMC,Subgenomic promoter recognition by the norovirus RNA-dependent RNA polymerases,http://dx.doi.org/10.1093/nar/gku1292,PMC4288183,25520198,CC BY,"The replication enzyme of RNA viruses must preferentially recognize their RNAs in an environment that contains an abundance of cellular RNAs. The factors responsible for specific RNA recognition are not well understood, in part because viral RNA synthesis takes place within enzyme complexes associated with modified cellular membrane compartments. Recombinant RNA-dependent RNA polymerases (RdRps) from the human norovirus and the murine norovirus (MNV) were found to preferentially recognize RNA segments that contain the promoter and a short template sequence for subgenomic RNA synthesis. Both the promoter and template sequence contribute to stable RdRp binding, accurate initiation of the subgenomic RNAs and efficient RNA synthesis. Using a method that combines RNA crosslinking and mass spectrometry, residues near the template channel of the MNV RdRp were found to contact the hairpin RNA motif. Mutations in the hairpin contact site in the MNV RdRp reduced MNV replication and virus production in cells. This work demonstrates that the specific recognition of the norovirus subgenomic promoter is through binding by the viral RdRp.",2015 Jan 9,"['Lin, Xiaoyan', 'Thorne, Lucy', 'Jin, Zhinan', 'Hammad, Loubna A.', 'Li, Serena', 'Deval, Jerome', 'Goodfellow, Ian G.', 'Kao, C. Cheng']",Nucleic Acids Res,,,True
4a698e56af8042a4c35a26127c4da5fc5ff7fa95,PMC,Long Non-Coding RNA BST2/BISPR is Induced by IFN and Regulates the Expression of the Antiviral Factor Tetherin,http://dx.doi.org/10.3389/fimmu.2014.00655,PMC4288319,25620967,CC BY,"Many long non-coding RNAs (lncRNAs) are expressed in cells but only a few have been well characterized. In these cases, lncRNAs have been shown to be key regulators of several cellular processes. Therefore, there is a great need to understand the function of more lncRNAs and their regulation in response to stimuli. Interferon (IFN) is a key molecule in the cellular antiviral response. IFN binding to its receptor activates transcription of several IFN-stimulated genes (ISGs) that function as potent antivirals. In addition, several ISGs are positive or negative regulators of the IFN pathway. This is essential to ensure a strong antiviral response and a later return of the cell to homeostasis. As the ISGs described to date are coding genes, we sought to determine whether IFN also regulates the expression of long non-coding ISGs. To this aim, we used RNA sequencing to analyze the transcriptome of control and HuH7 cells treated with IFNα2. The results show that IFN-treatment regulates the expression of several unknown non-coding transcripts. We have validated two lncRNAs upregulated after treatment with different doses of type I IFNα2 in different cells or with type III IFNλ. These lncRNAs were also induced by influenza and vesicular stomatitis virus mutants unable to block the IFN response, but not by several wild-type lytic viruses tested. These lncRNA genes were named lncISG15 and lncBST2 as they are located close to ISGs ISG15 and BST2, respectively. Interestingly, inhibition experiments showed that lncBST2 is a positive regulator of BST2. Therefore lncBST2 has been renamed BISPR, from BST2 IFN-stimulated positive regulator. Our results may have therapeutic implications as lncBST2/BISPR, but also lncISG15 and their coding neighbors, are increased in cells infected with hepatitis C virus and in the liver of infected patients. These results allow us to hypothesize that several lncRNAs could be activated by IFN to control the potency of the antiviral IFN response.",2015 Jan 9,"['Barriocanal, Marina', 'Carnero, Elena', 'Segura, Victor', 'Fortes, Puri']",Front Immunol,,,True
642113801b5c8906fb7eb9bf989d0c4fabd712e1,PMC,Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever,http://dx.doi.org/10.1371/journal.pntd.0003398,PMC4288732,25569707,CC BY,"BACKGROUND: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. METHODOLOGY/PRINCIPAL FINDINGS: Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Image: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only [Image: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Image: see text], with a maximum value up to [Image: see text]. CONCLUSIONS/SIGNIFICANCE: This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.",2015 Jan 8,"['Lo Iacono, Giovanni', 'Cunningham, Andrew A.', 'Fichet-Calvet, Elisabeth', 'Garry, Robert F.', 'Grant, Donald S.', 'Khan, Sheik Humarr', 'Leach, Melissa', 'Moses, Lina M.', 'Schieffelin, John S.', 'Shaffer, Jeffrey G.', 'Webb, Colleen T.', 'Wood, James L. N.']",PLoS Negl Trop Dis,,,True
6c87c1b2b6d84e2e3fbd504840d8434adc045833,PMC,Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever,http://dx.doi.org/10.1371/journal.pntd.0003398,PMC4288732,25569707,CC BY,"BACKGROUND: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. METHODOLOGY/PRINCIPAL FINDINGS: Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Image: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only [Image: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Image: see text], with a maximum value up to [Image: see text]. CONCLUSIONS/SIGNIFICANCE: This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.",2015 Jan 8,"['Lo Iacono, Giovanni', 'Cunningham, Andrew A.', 'Fichet-Calvet, Elisabeth', 'Garry, Robert F.', 'Grant, Donald S.', 'Khan, Sheik Humarr', 'Leach, Melissa', 'Moses, Lina M.', 'Schieffelin, John S.', 'Shaffer, Jeffrey G.', 'Webb, Colleen T.', 'Wood, James L. N.']",PLoS Negl Trop Dis,,,False
d8196519b0be213e70c77973a63cd4a13f5532c3,PMC,Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever,http://dx.doi.org/10.1371/journal.pntd.0003398,PMC4288732,25569707,CC BY,"BACKGROUND: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. METHODOLOGY/PRINCIPAL FINDINGS: Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Image: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only [Image: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Image: see text], with a maximum value up to [Image: see text]. CONCLUSIONS/SIGNIFICANCE: This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.",2015 Jan 8,"['Lo Iacono, Giovanni', 'Cunningham, Andrew A.', 'Fichet-Calvet, Elisabeth', 'Garry, Robert F.', 'Grant, Donald S.', 'Khan, Sheik Humarr', 'Leach, Melissa', 'Moses, Lina M.', 'Schieffelin, John S.', 'Shaffer, Jeffrey G.', 'Webb, Colleen T.', 'Wood, James L. N.']",PLoS Negl Trop Dis,,,True
3b4888c664b3d2fa758325160b185a453b6f8bb4,PMC,How to approach and treat viral infections in ICU patients,http://dx.doi.org/10.1186/1471-2334-14-321,PMC4289200,25431007,CC BY,Patients with severe viral infections are often hospitalized in intensive care units (ICUs) and recent studies underline the frequency of viral detection in ICU patients. Viral infections in the ICU often involve the respiratory or the central nervous system and can cause significant morbidity and mortality especially in immunocompromised patients. The mainstay of therapy of viral infections is supportive care and antiviral therapy when available. Increased understanding of the molecular mechanisms of viral infection has provided great potential for the discovery of new antiviral agents that target viral proteins or host proteins that regulate immunity and are involved in the viral life cycle. These novel treatments need to be further validated in animal and human randomized controlled studies.,2014 Nov 28,"['Kelesidis, Theodoros', 'Mastoris, Ioannis', 'Metsini, Aliki', 'Tsiodras, Sotirios']",BMC Infect Dis,,,True
027f86c44365e0ba6a6c26e24134c4c3e98a72ef,PMC,Virus-host interactomics: new insights and opportunities for antiviral drug discovery,http://dx.doi.org/10.1186/s13073-014-0115-1,PMC4295275,25593595,CC BY,"The current therapeutic arsenal against viral infections remains limited, with often poor efficacy and incomplete coverage, and appears inadequate to face the emergence of drug resistance. Our understanding of viral biology and pathophysiology and our ability to develop a more effective antiviral arsenal would greatly benefit from a more comprehensive picture of the events that lead to viral replication and associated symptoms. Towards this goal, the construction of virus-host interactomes is instrumental, mainly relying on the assumption that a viral infection at the cellular level can be viewed as a number of perturbations introduced into the host protein network when viral proteins make new connections and disrupt existing ones. Here, we review advances in interactomic approaches for viral infections, focusing on high-throughput screening (HTS) technologies and on the generation of high-quality datasets. We show how these are already beginning to offer intriguing perspectives in terms of virus-host cell biology and the control of cellular functions, and we conclude by offering a summary of the current situation regarding the potential development of host-oriented antiviral therapeutics.",2014 Nov 29,"['de Chassey, Benoît', 'Meyniel-Schicklin, Laurène', 'Vonderscher, Jacky', 'André, Patrice', 'Lotteau, Vincent']",Genome Med,,,True
5999e5bdbde2e8bfb3389bfe0ea96e229245cf67,PMC,"Genomics and infectious disease: a call to identify the ethical, legal and social implications for public health and clinical practice",http://dx.doi.org/10.1186/s13073-014-0106-2,PMC4295297,25593592,CC BY,"Advances in genomics are contributing to the development of more effective, personalized approaches to the prevention and treatment of infectious diseases. Genetic sequencing technologies are furthering our understanding of how human and pathogen genomic factors - and their interactions - contribute to individual differences in immunologic responses to vaccines, infections and drug therapies. Such understanding will influence future policies and procedures for infectious disease management. With the potential for tailored interventions for particular individuals, populations or subpopulations, ethical, legal and social implications (ELSIs) may arise for public health and clinical practice. Potential considerations include balancing health-related benefits and harms between individuals and the larger community, minimizing threats to individual privacy and autonomy, and ensuring just distribution of scarce resources. In this Opinion, we consider the potential application of pathogen and host genomic information to particular viral infections that have large-scale public health consequences but differ in ELSI-relevant characteristics such as ease of transmission, chronicity, severity, preventability and treatability. We argue for the importance of anticipating these ELSI issues in advance of new scientific discoveries, and call for the development of strategies for identifying and exploring ethical questions that should be considered as clinical, public health and policy decisions are made.",2014 Nov 18,"['Geller, Gail', 'Dvoskin, Rachel', 'Thio, Chloe L', 'Duggal, Priya', 'Lewis, Michelle H', 'Bailey, Theodore C', 'Sutherland, Andrea', 'Salmon, Daniel A', 'Kahn, Jeffrey P']",Genome Med,,,True
ab52aa56838160b5ec7a015a05ef76fc06129b5e,PMC,"MALDI-TOF mass spectrometry and identification of new bacteria species in air samples from Makkah, Saudi Arabia",http://dx.doi.org/10.1186/1756-0500-7-892,PMC4295573,25491533,CC BY,"BACKGROUND: During the Hajj season, respiratory symptoms are very common among pilgrims. Here, we investigated the viable bacterial population in air samples collected around the slaughterhouses used during the Hajj. METHODS AND RESULTS: We collected air samples on three days from four different sites: slaughterhouses at Al-Kakia, Al-Meaisim and Al-Sharaia, and from a waste disposal area designated for the remnants of slaughter. Samples were cultured on blood agar plates for 48 h, and bacterial isolates were identified using MALDI-TOF MS. A dendrogram using the spectra of the unidentified bacterial species was constructed, and PCR amplification and sequencing of the 16S rRNA gene was performed for one isolate per cluster. In total, 2500 colonies appeared on the nutrient agar plates, and 244 were purified for further analysis. Good identification was obtained for 202 (83%) isolates by MALDI-TOF MS. The most common genera were Bacillus (n = 94, 45%) and Staphyloccocus (n = 55, 26%). Poor identification was obtained for 42 (17%) isolates, and their spectra clustering revealed that these isolates belonged to 10 species. Four of these were considered to be new species. CONCLUSIONS: During the Hajj, the air was contaminated by many environmental bacterial agents, and MALDI-TOF MS was successfully adapted for their rapid identification.",2014 Dec 9,"['Angelakis, Emmanouil', 'Yasir, Muhammad', 'Azhar, Esam I', 'Papadioti, Anastasia', 'Bibi, Fehmida', 'Aburizaiza, Asad S', 'Metidji, Sarah', 'Memish, Ziad A', 'Ashshi, Ahmad M', 'Hassan, Ahmed M', 'Harakeh, Steve', 'Gautret, Philippe', 'Raoult, Didier']",BMC Res Notes,,,True
bc589336315df8e93a0fcd4fda5442bf982e9b6d,PMC,Accuracy of using automated methods for detecting adverse events from electronic health record data: a research protocol,http://dx.doi.org/10.1186/s13012-014-0197-6,PMC4296680,25567422,CC BY,"BACKGROUND: Adverse events are associated with significant morbidity, mortality and cost in hospitalized patients. Measuring adverse events is necessary for quality improvement, but current detection methods are inaccurate, untimely and expensive. The advent of electronic health records and the development of automated methods for encoding and classifying electronic narrative data, such as natural language processing, offer an opportunity to identify potentially better methods. The objective of this study is to determine the accuracy of using automated methods for detecting three highly prevalent adverse events: a) hospital-acquired pneumonia, b) catheter-associated bloodstream infections, and c) in-hospital falls. METHODS/DESIGN: This validation study will be conducted at two large Canadian academic health centres: the McGill University Health Centre (MUHC) and The Ottawa Hospital (TOH). The study population consists of all medical, surgical and intensive care unit patients admitted to these centres between 2008 and 2014. An automated detection algorithm will be developed and validated for each of the three adverse events using electronic data extracted from multiple clinical databases. A random sample of MUHC patients will be used to develop the automated detection algorithms (cohort 1, development set). The accuracy of these algorithms will be assessed using chart review as the reference standard. Then, receiver operating characteristic curves will be used to identify optimal cut points for each of the data sources. Multivariate logistic regression and the areas under curve (AUC) will be used to identify the optimal combination of data sources that maximize the accuracy of adverse event detection. The most accurate algorithms will then be validated on a second random sample of MUHC patients (cohort 1, validation set), and accuracy will be measured using chart review as the reference standard. The most accurate algorithms validated at the MUHC will then be applied to TOH data (cohort 2), and their accuracy will be assessed using a reference standard assessment of the medical chart. DISCUSSION: There is a need for more accurate, timely and efficient measures of adverse events in acute care hospitals. This is a critical requirement for evaluating the effectiveness of preventive interventions and for tracking progress in patient safety through time.",2015 Jan 8,"['Rochefort, Christian M', 'Buckeridge, David L', 'Forster, Alan J']",Implement Sci,,,True
44f34175ad29353c40276c6d19ee257e7511c8ef,PMC,Identification of VP1 peptides diagnostic of encephalomyocarditis virus from swine,http://dx.doi.org/10.1186/s12985-014-0226-8,PMC4297377,25547933,CC BY,"BACKGROUND: Encephalomyocarditis virus (EMCV) can cause myocarditis, respiratory failure, reproductive failure, and sudden death in pre-weaned piglets, which has been isolated in China. EMCV VP1 protein was one of the most important structural proteins and played an important role in the protective immunity. In this study, 10 monoclonal antibodies (McAbs) against EMCV VP1 were screened and identified. RESULTS: Epitope mapping results indicated that McAbs (6E11, 7A7, 7C9) specifically recognized the linear epitopes V(2)ENAEK(7), McAbs (1D1, 2A2, 5A1, 5A11, 5G1) recognized the epitope F(19)VAQPVY(25), and McAbs 1G8 and 3A9 recognized P(42)IGAFTVK(49). Protein sequence alignment of VP1 with 16 EMCV isolates indicated that the epitope F(19)VAQPVY(25) was conserved in all the reference strains. The epitopes P(42)IGAFTVK(49) and V(2)ENAEK(7) only had 1 or 2 variable amino acid among the reference strains. The 3D model analysis results showed that these epitopes presented as spheres were shown within the context of the complete particle. CONCLUSIONS: In this study, ten McAbs against EMCV VP1 were developed and three B-cells epitopes (2-7aa, 19-25aa and 42-49aa) were defined in VP1. All the results herein will promote the future investigations into the function of VP1 of EMCV and development of diagnostic methods of EMCV.",2014 Dec 30,"['Bai, Juan', 'Chen, Xinhui', 'Jiang, Kangfu', 'Zeshan, Basit', 'Jiang, Ping']",Virol J,,,True
574285d317ef91b77f2dc770a3dbf2a9b514de21,PMC,Molecular and clinical study on prevalence of feline herpesvirus type 1 and calicivirus in correlation with feline leukemia and immunodeficiency viruses,,PMC4299990,25610576,CC BY,"Upper respiratory tract diseases (URTD) are common clinical problem in cats worldwide. Feline calicivirus (FCV) and feline herpesvirus type 1 (FHV-1) are the main primary pathogens. Feline immunodeficiency virus (FIV) and Feline leukemia virus (FeLV) are also among the most common infectious diseases of cats which suppress the immunity. Oropharyngeal and conjunctival swabs and blood samples were taken from 16 cats with clinical signs of URTD and 26 clinically healthy cats. PCR and RT-PCR were used to detect FHV/FIV or FCV/FeLV infections, respectively. Feline calicivirus was detected in all cats with URTD and 87.00% and 93.00% of them were positive for FIV and FeLV, respectively. Feline herpesvirus rate of infection was 43.00% in sick cats. In clinically normal cats, prevalence rates of FCV and FHV were about 50.00%, but FIV and FeLV rates (42.00% and 65.00% respectively) were higher compared to other studies. Stomatitis was observed in 50.00% of cats with URTD. The main causative agent of corneal ulcers is FHV-1, but in 50.00% of cats with corneal ulcers, FCV was detected alone. It seems new variants of Caliciviruses are the main causative agents to attack uncommon tissues like cornea, although retroviral infections may be in the background of these various signs. The high retroviral prevalence may be due to existence of large population of stray cats. This is the first molecular study of FeLV and FCV in Iran and seems that FCV and FHV prevalence rates in FIV or FeLV infected cats is more than other non-infected ones.",2014 Autumn,"['Najafi, Hamideh', 'Madadgar, Omid', 'Jamshidi, Shahram', 'Ghalyanchi Langeroudi, Arash', 'Darzi Lemraski, Mahdieh']",Vet Res Forum,,,True
215d86822474f970baa8ed894e23940bc4a85c79,PMC,Molecular detection of infectious bronchitis and Newcastle disease viruses in broiler chickens with respiratory signs using Duplex RT-PCR,,PMC4299999,25610585,CC BY,"Infectious bronchitis (IB) and Newcastle disease (ND) are highly contagious and the most economically important diseases of the poultry affecting respiratory tract and causing economic losses in poultry industry throughout the world. In the present study, the simultaneous detection and differentiation of causative agents of these diseases were investigated using duplex-RT-PCR. RNA was extracted from vaccinal and reference strains of infectious bronchitis virus (IBV) and Newcastle disease virus (NDV) and then cDNA was synthesized. Using two universal primer sets for detection of IBV and NDV, the duplex-RT-PCR was developed. In order to assess the efficiency of the developed duplex RT-PCR, a number of 12 broiler farms with the symptoms of respiratory tract infection was sampled (trachea, lung and kidney were sampled from affected birds suspicious for IBV and NDV infections). After RNA extraction from tissues and cDNA synthesis, the presence of IBV and NDV genome were investigated using duplex-PCR. The results showed that three of twelve examined broiler farms were positive for IBV and two farms were positive for NDV and IBV. The results revealed that the duplex-RT-PCR is a quick and sensitive procedure for simultaneously detecting IBV and NDV in birds with respiratory infections.",2014 Autumn,"['Saba Shirvan, Aylar', 'Mardani, Karim']",Vet Res Forum,,,True
368cbceb0d0e8ad64b484f330c03d950394bf397,PMC,Using internet search queries for infectious disease surveillance: screening diseases for suitability,http://dx.doi.org/10.1186/s12879-014-0690-1,PMC4300155,25551277,CC BY,"BACKGROUND: Internet-based surveillance systems provide a novel approach to monitoring infectious diseases. Surveillance systems built on internet data are economically, logistically and epidemiologically appealing and have shown significant promise. The potential for these systems has increased with increased internet availability and shifts in health-related information seeking behaviour. This approach to monitoring infectious diseases has, however, only been applied to single or small groups of select diseases. This study aims to systematically investigate the potential for developing surveillance and early warning systems using internet search data, for a wide range of infectious diseases. METHODS: Official notifications for 64 infectious diseases in Australia were downloaded and correlated with frequencies for 164 internet search terms for the period 2009–13 using Spearman’s rank correlations. Time series cross correlations were performed to assess the potential for search terms to be used in construction of early warning systems. RESULTS: Notifications for 17 infectious diseases (26.6%) were found to be significantly correlated with a selected search term. The use of internet metrics as a means of surveillance has not previously been described for 12 (70.6%) of these diseases. The majority of diseases identified were vaccine-preventable, vector-borne or sexually transmissible; cross correlations, however, indicated that vector-borne and vaccine preventable diseases are best suited for development of early warning systems. CONCLUSIONS: The findings of this study suggest that internet-based surveillance systems have broader applicability to monitoring infectious diseases than has previously been recognised. Furthermore, internet-based surveillance systems have a potential role in forecasting emerging infectious disease events, especially for vaccine-preventable and vector-borne diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0690-1) contains supplementary material, which is available to authorized users.",2014 Dec 31,"['Milinovich, Gabriel J', 'Avril, Simon M R', 'Clements, Archie C A', 'Brownstein, John S', 'Tong, Shilu', 'Hu, Wenbiao']",BMC Infect Dis,,,True
cec21bb25c57f0e17f672a7ed7b91a01bd371ee7,PMC,Bovine respiratory syncytial virus and bovine coronavirus in Swedish organic and conventional dairy herds,http://dx.doi.org/10.1186/s13028-014-0091-x,PMC4300160,25582919,CC BY,"BACKGROUND: Infections with bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BoCV) are endemic to the cattle populations in most countries, causing respiratory and/or enteric disease. It has been demonstrated that herds can remain free from these infections for several years also in high prevalence areas. Organically managed (OM) dairy herds have been shown to have lower seroprevalence of both viruses compared to conventionally managed (CM) herds. The objective of this study was to challenge the hypothesis of a lower occurrence of BRSV and BoCV in OM compared to CM dairy herds. In November 2011, May 2012 and May 2013 milk samples from four homebred primiparous cows were collected in 75 to 65 OM and 69 to 62 CM herds. The antibody status regarding BRSV and BoCV was analysed with commercial indirect ELISAs. Herds were classified as positive if at least one individual sample was positive. RESULTS: The prevalence of positive herds ranged from 73.4% to 82.3% for BRSV and from 76.8% to 85.3% for BoCV among OM and CM herds, over the three sampling occasions. There was no statistically significant difference between OM and CM herds at any sampling occasion. The incidence risk of newly infected herds did not differ statistically between OM and CM herds at any sampling occasion, neither for BRSV nor for BoCV. The incidence of herds turning sero-negative between samplings corresponded to the incidence of newly infected. Bulk tank milk (BTM) samples were also sampled in the herds and analysed. Several herds were negative on individual samples but positive in BTM. Herd-level data on production, health and reproduction were retrieved from VÄXA Sweden and the study herds were representative of the source population. CONCLUSION: There was no difference in prevalence of or incidence risk for BRSV or BoCV between Swedish OM and CM herds. Because the incidence of herds becoming seropositive was balanced by herds becoming seronegative it should be possible to lower the prevalence of these two infections among Swedish dairy cattle herds if biosecurity is improved. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-014-0091-x) contains supplementary material, which is available to authorized users.",2015 Jan 13,"['Wolff, Cecilia', 'Emanuelson, Ulf', 'Ohlson, Anna', 'Alenius, Stefan', 'Fall, Nils']",Acta Vet Scand,,,True
e56624da7d4f6a86a9cc0a91f3e5a8e98823cea5,PMC,Identification of novel viral receptors with cell line expressing viral receptor-binding protein,http://dx.doi.org/10.1038/srep07935,PMC4300512,25604889,CC BY,"The viral cell receptors and infection can be blocked by the expression of the viral receptor-binding protein. Thus, the viral cell receptor is an attractive target for anti-viral strategies, and the identification of viral cell receptor is critical for better understanding and controlling viral disease. As a model system for viral entry and anti-retroviral approaches, avian sarcoma/leukosis virus (ASLV, including the A-J ten subgroups) has been studied intensively and many milestone discoveries have been achieved based on work with ASLV. Here, we used a DF1 cell line expressed viral receptor-binding protein to efficiently identify chicken Annexin A2 (chANXA2) as a novel receptor for retrovirus ALV-J (avian leukosis virus subgroup J). Our data demonstrate that antibodies or siRNA to chANXA2 significantly inhibited ALV-J infection and replication, and over-expression of chANXA2 permitted the entry of ALV-J into its non-permissible cells. Our findings have not only identified chANXA2 as a novel biomarker for anti-ALV-J, but also demonstrated that cell lines with the expression of viral receptor-binding protein could be as efficient tools for isolating functional receptors to identify novel anti-viral targets.",2015 Jan 21,"['Mei, Mei', 'Ye, Jianqiang', 'Qin, Aijian', 'Wang, Lin', 'Hu, Xuming', 'Qian, Kun', 'Shao, Hongxia']",Sci Rep,,,True
6a45607f711714e68936b74d1af18df649a96b07,PMC,Adverse effects of Influenza A(H1N1)pdm09 virus infection on growth performance of Norwegian pigs - a longitudinal study at a boar testing station,http://dx.doi.org/10.1186/s12917-014-0284-6,PMC4300606,25472551,CC BY,"BACKGROUND: Influenza A(H1N1)pdm09 virus infection in Norwegian pigs was largely subclinical. This study tested the hypothesis that the infection causes negligible impact on pigs’ growth performance in terms of feed conversion efficiency, daily feed intake, daily growth, age on reaching 100 kg bodyweight and overall feed intake. A sample of 1955 pigs originating from 43 breeding herds was classified into five infection status groups; seronegative pigs (n = 887); seropositive pigs (n = 874); pigs positive for virus at bodyweight between 33 kg and 60 kg (n = 123); pigs positive for virus at bodyweight between 61 kg and 80 kg (n = 34) and pigs positive for virus at bodyweight between 81 kg and 100 kg (n = 37). Each pig had daily recordings of feed intake and bodyweight from 33 kg to 100 kg. Marginal effects of the virus infection on the outcomes were estimated by multi-level linear regression, which accounted for known fixed effects (breed, birthdate, average daily feed intake and growth phase) and random effects (cluster effects of pig and herd). RESULTS: The seropositive and virus positive pigs had decreased (P value<0.05) growth performance compared to seronegative pigs even though feed intake was not decreased. Reduced feed conversion efficiency led to lower average daily growth, additional feed requirement and longer time needed to reach the 100 kg bodyweight. The effects were more marked (P value<0.03) in pigs infected at a younger age and lasted a longer period. Despite increased feed intake observed, their growth rates were lower and they took more time to reach 100 kg bodyweight compared to the seronegative pigs. CONCLUSION: Our study rejected the null hypothesis that the virus infection had negligible adverse effects on growth performance of Norwegian pigs.",2014 Dec 4,"['Er, Chiek', 'Lium, Bjørn', 'Tavornpanich, Saraya', 'Hofmo, Peer Ola', 'Forberg, Hilde', 'Hauge, Anna Germundsson', 'Grøntvedt, Carl Andreas', 'Framstad, Tore', 'Brun, Edgar']",BMC Vet Res,,,True
888f3a42d4361d36b3ffbe619427ace11fae0e1b,PMC,"Knowledge and attitude of healthcare workers about middle east respiratory syndrome in multispecialty hospitals of Qassim, Saudi Arabia",http://dx.doi.org/10.1186/1471-2458-14-1281,PMC4300996,25510239,CC BY,"BACKGROUND: With the increase in prevalence of Middle East Respiratory Syndrome (MERS), healthcare workers (HCWs) are at risk of acquiring and subsequently transmitting this lethal virus. In view of this, HCWs were evaluated for their knowledge of and attitude towards MERS in Saudi Arabia. METHODS: A cross sectional study was performed in two hospitals of Qassim region in Saudi Arabia. A total of 280 healthcare workers were selected to participate in this study. Knowledge and attitude were assessed by using self-administered and pretested questionnaire. Descriptive statistics were carried out to express participants’ demographic information, mean knowledge score and mean attitude score of HCWs. Inferential statistics (Mann–Whitney U test and Kruskal Wallis tests, p < 0.05) were used to examine differences between study variables. Chi squares tests were used to assess the association between study variables and attitude questions. Spearman’s rho correlation was used to identify the association between the knowledge, attitude scores. RESULT: Participants demonstrated good knowledge and positive attitude towards MERS. The mean scores of knowledge and attitude were 9.45 ± 1.69 (based on 13 knowledge questions) and 1.82 ± 0.72 (based on 7 attitude questions). The correlation between knowledge and attitude was significant (correlation coefficient: 0.12; P <0.001). HCWs were less educated about the management (42.4%), source (66%) and consequences of MERS (67.3%), while a majority of them were well aware of the hallmark symptoms (96%), precautionary measures (96%) and hygiene issues (94%). Although the majority of respondents showed positive attitude towards the use of protective measures (1.52 ± 0.84), their attitude was negative towards their active participation in infection control program (2.03 ± 0.97). Gender and experience were significantly associated with knowledge and attitude (P < 0.05). CONCLUSIONS: The findings of this study showed that healthcare workers in Qassim region of Saudi Arabia have good knowledge and positive attitude towards MERS. Yet there are areas where low knowledge and negative attitude of HCWs was observed. However, studies are required to assess the knowledge and attitude of HCWs at national level so that effective interventions could be designed as surveillance and infection control measures are critical to global public health.",2014 Dec 16,"['Khan, Muhammad Umair', 'Shah, Shahjahan', 'Ahmad, Akram', 'Fatokun, Omotayo']",BMC Public Health,,,True
4f0e7fc5e32e927fd76e1f5c156cb9caee8eda2a,PMC,Animal board invited review: advances in proteomics for animal and food sciences,http://dx.doi.org/10.1017/S1751731114002602,PMC4301196,25359324,CC BY,"Animal production and health (APH) is an important sector in the world economy, representing a large proportion of the budget of all member states in the European Union and in other continents. APH is a highly competitive sector with a strong emphasis on innovation and, albeit with country to country variations, on scientific research. Proteomics (the study of all proteins present in a given tissue or fluid – i.e. the proteome) has an enormous potential when applied to APH. Nevertheless, for a variety of reasons and in contrast to disciplines such as plant sciences or human biomedicine, such potential is only now being tapped. To counter such limited usage, 6 years ago we created a consortium dedicated to the applications of Proteomics to APH, specifically in the form of a Cooperation in Science and Technology (COST) Action, termed FA1002 – Proteomics in Farm Animals: www.cost-faproteomics.org. In 4 years, the consortium quickly enlarged to a total of 31 countries in Europe, as well as Israel, Argentina, Australia and New Zealand. This article has a triple purpose. First, we aim to provide clear examples on the applications and benefits of the use of proteomics in all aspects related to APH. Second, we provide insights and possibilities on the new trends and objectives for APH proteomics applications and technologies for the years to come. Finally, we provide an overview and balance of the major activities and accomplishments of the COST Action on Farm Animal Proteomics. These include activities such as the organization of seminars, workshops and major scientific conferences, organization of summer schools, financing Short-Term Scientific Missions (STSMs) and the generation of scientific literature. Overall, the Action has attained all of the proposed objectives and has made considerable difference by putting proteomics on the global map for animal and veterinary researchers in general and by contributing significantly to reduce the East–West and North–South gaps existing in the European farm animal research. Future activities of significance in the field of scientific research, involving members of the action, as well as others, will likely be established in the future.",2015 Jan 31,"['Almeida, A. M.', 'Bassols, A.', 'Bendixen, E.', 'Bhide, M.', 'Ceciliani, F.', 'Cristobal, S.', 'Eckersall, P. D.', 'Hollung, K.', 'Lisacek, F.', 'Mazzucchelli, G.', 'McLaughlin, M.', 'Miller, I.', 'Nally, J. E.', 'Plowman, J.', 'Renaut, J.', 'Rodrigues, P.', 'Roncada, P.', 'Staric, J.', 'Turk, R.']",Animal,,,True
d06b1f07cc3e2f1ac0dbcd16995fc351a1bafe91,PMC,Characterizing the Transmission Dynamics and Control of Ebola Virus Disease,http://dx.doi.org/10.1371/journal.pbio.1002057,PMC4301953,25607595,CC0,"Carefully calibrated transmission models have the potential to guide public health officials on the nature and scale of the interventions required to control epidemics. In the context of the ongoing Ebola virus disease (EVD) epidemic in Liberia, Drake and colleagues, in this issue of PLOS Biology, employed an elegant modeling approach to capture the distributions of the number of secondary cases that arise in the community and health care settings in the context of changing population behaviors and increasing hospital capacity. Their findings underscore the role of increasing the rate of safe burials and the fractions of infectious individuals who seek hospitalization together with hospital capacity to achieve epidemic control. However, further modeling efforts of EVD transmission and control in West Africa should utilize the spatial-temporal patterns of spread in the region by incorporating spatial heterogeneity in the transmission process. Detailed datasets are urgently needed to characterize temporal changes in population behaviors, contact networks at different spatial scales, population mobility patterns, adherence to infection control measures in hospital settings, and hospitalization and reporting rates.",2015 Jan 21,"['Chowell, Gerardo', 'Nishiura, Hiroshi']",PLoS Biol,,,True
a401eee90cc270520c65bc001f31a617f4edb7df,PMC,A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus,http://dx.doi.org/10.12688/f1000research.5741.2,PMC4304229,25653841,CC BY,"We are currently faced with a global infectious disease crisis which has been anticipated for decades. While many promising biotherapeutics are being tested, the search for a small molecule has yet to deliver an approved drug or therapeutic for the Ebola or similar filoviruses that cause haemorrhagic fever. Two recent high throughput screens published in 2013 did however identify several hits that progressed to animal studies that are FDA approved drugs used for other indications. The current computational analysis uses these molecules from two different structural classes to construct a common features pharmacophore. This ligand-based pharmacophore implicates a possible common target or mechanism that could be further explored. A recent structure based design project yielded nine co-crystal structures of pyrrolidinone inhibitors bound to the viral protein 35 (VP35). When receptor-ligand pharmacophores based on the analogs of these molecules and the protein structures were constructed, the molecular features partially overlapped with the common features of solely ligand-based pharmacophore models based on FDA approved drugs. These previously identified FDA approved drugs with activity against Ebola were therefore docked into this protein. The antimalarials chloroquine and amodiaquine docked favorably in VP35. We propose that these drugs identified to date as inhibitors of the Ebola virus may be targeting VP35. These computational models may provide preliminary insights into the molecular features that are responsible for their activity against Ebola virus in vitro and in vivo and we propose that this hypothesis could be readily tested.",2014 Dec 12,"['Ekins, Sean', 'Freundlich, Joel S.', 'Coffee, Megan']",F1000Res,,,True
d1eecf25e925b3c331a75d38e687648718e2d4f1,PMC,"A comparison of smartphones to paper-based questionnaires for routine influenza sentinel surveillance, Kenya, 2011–2012",http://dx.doi.org/10.1186/s12911-014-0107-5,PMC4305246,25539745,CC BY,"BACKGROUND: For disease surveillance, manual data collection using paper-based questionnaires can be time consuming and prone to errors. We introduced smartphone data collection to replace paper-based data collection for an influenza sentinel surveillance system in four hospitals in Kenya. We compared the quality, cost and timeliness of data collection between the smartphone data collection system and the paper-based system. METHODS: Since 2006, the Kenya Ministry of Health (MoH) with technical support from the Kenya Medical Research Institute/Centers for Disease Control and Prevention (KEMRI/CDC) conducted hospital-based sentinel surveillance for influenza in Kenya. In May 2011, the MOH replaced paper-based collection with an electronic data collection system using Field Adapted Survey Toolkit (FAST) on HTC Touch Pro2 smartphones at four sentinel sites. We compared 880 paper-based questionnaires dated Jan 2010-Jun 2011 and 880 smartphone questionnaires dated May 2011-Jun 2012 from the four surveillance sites. For each site, we compared the quality, cost and timeliness of each data collection system. RESULTS: Incomplete records were more likely seen in data collected using pen-and-paper compared to data collected using smartphones (adjusted incidence rate ratio (aIRR) 7, 95% CI: 4.4-10.3). Errors and inconsistent answers were also more likely to be seen in data collected using pen-and-paper compared to data collected using smartphones (aIRR: 25, 95% CI: 12.5-51.8). Smartphone data was uploaded into the database in a median time of 7 days while paper-based data took a median of 21 days to be entered (p < 0.01). It cost USD 1,501 (9.4%) more to establish the smartphone data collection system ($17,500) than the pen-and-paper system (USD $15,999). During two years, however, the smartphone data collection system was $3,801 (7%) less expensive to operate ($50,200) when compared to pen-and-paper system ($54,001). CONCLUSIONS: Compared to paper-based data collection, an electronic data collection system produced fewer incomplete data, fewer errors and inconsistent responses and delivered data faster. Although start-up costs were higher, the overall costs of establishing and running the electronic data collection system were lower compared to paper-based data collection system. Electronic data collection using smartphones has potential to improve timeliness, data integrity and reduce costs.",2014 Dec 24,"['Njuguna, Henry N', 'Caselton, Deborah L', 'Arunga, Geoffrey O', 'Emukule, Gideon O', 'Kinyanjui, Dennis K', 'Kalani, Rosalia M', 'Kinkade, Carl', 'Muthoka, Phillip M', 'Katz, Mark A', 'Mott, Joshua A']",BMC Med Inform Decis Mak,,,True
9ac6114492dec5eb4c4afe605b1a83c689df0dec,PMC,Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections,http://dx.doi.org/10.1098/rsif.2014.0886,PMC4305404,25519990,CC BY,"In recent years, the within-host viral dynamics of dengue infections have been increasingly characterized, and the relationship between aspects of these dynamics and the manifestation of severe disease has been increasingly probed. Despite this progress, there are few mathematical models of within-host dengue dynamics, and the ones that exist focus primarily on the general role of immune cells in the clearance of infected cells, while neglecting other components of the immune response in limiting viraemia. Here, by considering a suite of mathematical within-host dengue models of increasing complexity, we aim to isolate the critical components of the innate and the adaptive immune response that suffice in the reproduction of several well-characterized features of primary and secondary dengue infections. By building up from a simple target cell limited model, we show that only the innate immune response is needed to recover the characteristic features of a primary symptomatic dengue infection, while a higher rate of viral infectivity (indicative of antibody-dependent enhancement) and infected cell clearance by T cells are further needed to recover the characteristic features of a secondary dengue infection. We show that these minimal models can reproduce the increased risk of disease associated with secondary heterologous infections that arises as a result of a cytokine storm, and, further, that they are consistent with virological indicators that predict the onset of severe disease, such as the magnitude of peak viraemia, time to peak viral load, and viral clearance rate. Finally, we show that the effectiveness of these virological indicators to predict the onset of severe disease depends on the contribution of T cells in fuelling the cytokine storm.",2015 Feb 6,"['Ben-Shachar, Rotem', 'Koelle, Katia']",J R Soc Interface,,,True
306bedd61bce68752ab0206d35b28c79f4eebb0a,PMC,Minimal within-host dengue models highlight the specific roles of the immune response in primary and secondary dengue infections,http://dx.doi.org/10.1098/rsif.2014.0886,PMC4305404,25519990,CC BY,"In recent years, the within-host viral dynamics of dengue infections have been increasingly characterized, and the relationship between aspects of these dynamics and the manifestation of severe disease has been increasingly probed. Despite this progress, there are few mathematical models of within-host dengue dynamics, and the ones that exist focus primarily on the general role of immune cells in the clearance of infected cells, while neglecting other components of the immune response in limiting viraemia. Here, by considering a suite of mathematical within-host dengue models of increasing complexity, we aim to isolate the critical components of the innate and the adaptive immune response that suffice in the reproduction of several well-characterized features of primary and secondary dengue infections. By building up from a simple target cell limited model, we show that only the innate immune response is needed to recover the characteristic features of a primary symptomatic dengue infection, while a higher rate of viral infectivity (indicative of antibody-dependent enhancement) and infected cell clearance by T cells are further needed to recover the characteristic features of a secondary dengue infection. We show that these minimal models can reproduce the increased risk of disease associated with secondary heterologous infections that arises as a result of a cytokine storm, and, further, that they are consistent with virological indicators that predict the onset of severe disease, such as the magnitude of peak viraemia, time to peak viral load, and viral clearance rate. Finally, we show that the effectiveness of these virological indicators to predict the onset of severe disease depends on the contribution of T cells in fuelling the cytokine storm.",2015 Feb 6,"['Ben-Shachar, Rotem', 'Koelle, Katia']",J R Soc Interface,,,True
49241d35c68b9ffeb0057758abdf00fc18cce2f0,PMC,HIV-1 Replication and the Cellular Eukaryotic Translation Apparatus,http://dx.doi.org/10.3390/v7010199,PMC4306834,25606970,CC BY,"Eukaryotic translation is a complex process composed of three main steps: initiation, elongation, and termination. During infections by RNA- and DNA-viruses, the eukaryotic translation machinery is used to assure optimal viral protein synthesis. Human immunodeficiency virus type I (HIV-1) uses several non-canonical pathways to translate its own proteins, such as leaky scanning, frameshifting, shunt, and cap-independent mechanisms. Moreover, HIV-1 modulates the host translation machinery by targeting key translation factors and overcomes different cellular obstacles that affect protein translation. In this review, we describe how HIV-1 proteins target several components of the eukaryotic translation machinery, which consequently improves viral translation and replication.",2015 Jan 19,"['Guerrero, Santiago', 'Batisse, Julien', 'Libre, Camille', 'Bernacchi, Serena', 'Marquet, Roland', 'Paillart, Jean-Christophe']",Viruses,,,True
12c2a6ee1e3e7cf0f915e5c5454627b7e1ed9db3,PMC,Epimedium koreanum Nakai Displays Broad Spectrum of Antiviral Activity in Vitro and in Vivo by Inducing Cellular Antiviral State,http://dx.doi.org/10.3390/v7010352,PMC4306843,25609307,CC BY,"Epimedium koreanum Nakai has been extensively used in traditional Korean and Chinese medicine to treat a variety of diseases. Despite the plant’s known immune modulatory potential and chemical make-up, scientific information on its antiviral properties and mode of action have not been completely investigated. In this study, the broad antiviral spectrum and mode of action of an aqueous extract from Epimedium koreanum Nakai was evaluated in vitro, and moreover, the protective effect against divergent influenza A subtypes was determined in BALB/c mice. An effective dose of Epimedium koreanum Nakaimarkedly reduced the replication of Influenza A Virus (PR8), Vesicular Stomatitis Virus (VSV), Herpes Simplex Virus (HSV) and Newcastle Disease Virus (NDV) in RAW264.7 and HEK293T cells. Mechanically, we found that an aqueous extract from Epimedium koreanum Nakai induced the secretion of type I IFN and pro-inflammatory cytokines and the subsequent stimulation of the antiviral state in cells. Among various components present in the extract, quercetin was confirmed to have striking antiviral properties. The oral administration of Epimedium koreanum Nakai exhibited preventive effects on BALB/c mice against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2). Therefore, an extract of Epimedium koreanum Nakai and its components play roles as immunomodulators in the innate immune response, and may be potential candidates for prophylactic or therapeutic treatments against diverse viruses in animal and humans.",2015 Jan 20,"['Cho, Won-Kyung', 'Weeratunga, Prasanna', 'Lee, Byeong-Hoon', 'Park, Jun-Seol', 'Kim, Chul-Joong', 'Ma, Jin Yeul', 'Lee, Jong-Soo']",Viruses,,,True
75cf3b144e29ca2e460e2700827543bb72ef0844,PMC,Cluster of Human Infections with Avian Influenza A (H7N9) Cases: A Temporal and Spatial Analysis,http://dx.doi.org/10.3390/ijerph120100816,PMC4306894,25599373,CC BY,"Objectives: This study aims to describe the spatial and temporal characteristics of human infections with H7N9 virus in China using data from February 2013 to March 2014 from the websites of every province’s Population and Family Planning Commission. Methods: A human infection with H7N9 virus dataset was summarized by county to analyze its spatial clustering, and by date of illness onset to analyze its space-time clustering using the ESRI(®) Geographic Information System (GIS) software ArcMap™ 10.1 and SatScan. Results: Based on active surveillance data, the distribution map of H7N9 cases shows that compared to the rest of China, the areas from near the Yangtze River delta (YRD) to farther south around the Pearl River delta (PRD) had the highest densities of H7N9 cases. The case data shows a strong space-time clustering in the areas on and near the YRD from 26 March to 18 April 2013 and a weak space-time clustering only in the areas on and near the PRD between 3 and 4 February 2014. However, for the rest of the study period, H7N9 cases were spatial-temporally randomly distributed. Conclusions: Our results suggested that the spatial-temporal clustering of H7N9 in China between 2013 and 2014 is fundamentally different.",2015 Jan 15,"['Zhang, Yi', 'Shen, Zhixiong', 'Ma, Chunna', 'Jiang, Chengsheng', 'Feng, Cindy', 'Shankar, Nivedita', 'Yang, Peng', 'Sun, Wenjie', 'Wang, Quanyi']",Int J Environ Res Public Health,,,True
57a3e8ebd6f29c8e8126ff652f6f79b1b8fbffc6,PMC,Universal health coverage in ‘One ASEAN’: are migrants included?,http://dx.doi.org/10.3402/gha.v8.25749,PMC4308585,25626624,CC BY,"BACKGROUND: As the Association of South East Asian Nations (ASEAN) gears toward full regional integration by 2015, the cross-border mobility of workers and citizens at large is expected to further intensify in the coming years. While ASEAN member countries have already signed the Declaration on the Protection and Promotion of the Rights of Migrant Workers, the health rights of migrants still need to be addressed, especially with ongoing universal health coverage (UHC) reforms in most ASEAN countries. This paper seeks to examine the inclusion of migrants in the UHC systems of five ASEAN countries which exhibit diverse migration profiles and are currently undergoing varying stages of UHC development. DESIGN: A scoping review of current migration trends and policies as well as ongoing UHC developments and migrant inclusion in UHC in Indonesia, Malaysia, Philippines, Singapore, and Thailand was conducted. RESULTS: In general, all five countries, whether receiving or sending, have schemes that cover migrants to varying extents. Thailand even allows undocumented migrants to opt into its Compulsory Migrant Health Insurance scheme, while Malaysia and Singapore are still yet to consider including migrants in their government-run UHC systems. In terms of predominantly sending countries, the Philippines's social health insurance provides outbound migrants with portable insurance yet with limited benefits, while Indonesia still needs to strengthen the implementation of its compulsory migrant insurance which has a health insurance component. Overall, the five ASEAN countries continue to face implementation challenges, and will need to improve on their UHC design in order to ensure genuine inclusion of migrants, including undocumented migrants. However, such reforms will require strong political decisions from agencies outside the health sector that govern migration and labor policies. Furthermore, countries must engage in multilateral and bilateral dialogue as they redefine UHC beyond the basis of citizenship and reimagine UHC systems that transcend national borders. CONCLUSIONS: By enhancing migrant coverage, ASEAN countries can make UHC systems truly ‘universal’. Migrant inclusion in UHC is a human rights imperative, and it is in ASEAN's best interest to protect the health of migrants as it pursues the path toward collective social progress and regional economic prosperity.",2015 Jan 24,"['Guinto, Ramon Lorenzo Luis R.', 'Curran, Ufara Zuwasti', 'Suphanchaimat, Rapeepong', 'Pocock, Nicola S.']",Glob Health Action,,,True
9b4e7443a59fb1fd764f172bd67a0f73da1ec3cd,PMC,Qualitative and Quantitative Analysis of the Major Constituents in Chinese Medical Preparation Lianhua-Qingwen Capsule by UPLC-DAD-QTOF-MS,http://dx.doi.org/10.1155/2015/731765,PMC4308632,25654135,CC BY,"Lianhua-Qingwen capsule (LQC) is a commonly used Chinese medical preparation to treat viral influenza and especially played a very important role in the fight against severe acute respiratory syndrome (SARS) in 2002-2003 in China. In this paper, a rapid ultraperformance liquid chromatography coupled with diode-array detector and quadrupole time-of-flight mass spectrometry (UPLC-DAD-QTOF-MS) method was established for qualitative and quantitative analysis of the major constituents of LQC. A total of 61 compounds including flavonoids, phenylpropanoids, anthraquinones, triterpenoids, iridoids, and other types of compounds were unambiguously or tentatively identified by comparing the retention times and accurate mass measurement with reference compounds or literature data. Among them, twelve representative compounds were further quantified as chemical markers in quantitative analysis, including salidroside, chlorogenic acid, forsythoside E, cryptochlorogenic acid, amygdalin, sweroside, hyperin, rutin, forsythoside A, phillyrin, rhein, and glycyrrhizic acid. The UPLC-DAD method was evaluated with linearity, limit of detection (LOD), limit of quantification (LOQ), precision, stability, repeatability, and recovery tests. The results showed that the developed quantitative method was linear, sensitive, and precise for the quality control of LQC.",2015 Jan 8,"['Jia, Weina', 'Wang, Chunhua', 'Wang, Yuefei', 'Pan, Guixiang', 'Jiang, Miaomiao', 'Li, Zheng', 'Zhu, Yan']",ScientificWorldJournal,,,True
ed5375ac7d887e311e407121b4c80e8d0ca0afed,PMC,The RNA shapes studio,http://dx.doi.org/10.1093/bioinformatics/btu649,PMC4308662,25273103,CC BY,"Motivation: Abstract shape analysis, first proposed in 2004, allows one to extract several relevant structures from the folding space of an RNA sequence, preferable to focusing in a single structure of minimal free energy. We report recent extensions to this approach. Results: We have rebuilt the original RNAshapes as a repository of components that allows us to integrate several established tools for RNA structure analysis: RNAshapes, RNAalishapes and pknotsRG, including its recent extension pKiss. As a spin-off, we obtain heretofore unavailable functionality: e. g. with pKiss, we can now perform abstract shape analysis for structures holding pseudoknots up to the complexity of kissing hairpin motifs. The new tool pAliKiss can predict kissing hairpin motifs from aligned sequences. Along with the integration, the functionality of the tools was also extended in manifold ways. Availability and implementation: As before, the tool is available on the Bielefeld Bioinformatics server at http://bibiserv.cebitec.uni-bielefeld.de/rnashapesstudio. Contact: bibi-help@cebitec.uni-bielefeld.de",2015 Feb 1,"['Janssen, Stefan', 'Giegerich, Robert']",Bioinformatics,,,True
21fd38266c7336a6ace6ca87ee9ac07a580cfdeb,PMC,Comparative Analysis of the Intestinal Bacterial and RNA Viral Communities from Sentinel Birds Placed on Selected Broiler Chicken Farms,http://dx.doi.org/10.1371/journal.pone.0117210,PMC4311960,25635690,CC0,"There is a great deal of interest in characterizing the complex microbial communities in the poultry gut, and in understanding the effects of these dynamic communities on poultry performance, disease status, animal welfare, and microbes with human health significance. Investigations characterizing the poultry enteric virome have identified novel poultry viruses, but the roles these viruses play in disease and performance problems have yet to be fully characterized. The complex bacterial community present in the poultry gut influences gut development, immune status, and animal health, each of which can be an indicator of overall performance. The present metagenomic investigation was undertaken to provide insight into the colonization of specific pathogen free chickens by enteric microorganisms under field conditions and to compare the pre-contact intestinal microbiome with the altered microbiome following contact with poultry raised in the field. Analysis of the intestinal virome from contact birds (“sentinels”) placed on farms revealed colonization by members of the Picornaviridae, Picobirnaviridae, Reoviridae, and Astroviridae that were not present in pre-contact birds or present in proportionally lower numbers. Analysis of the sentinel gut bacterial community revealed an altered community in the post-contact birds, notably by members of the Lachnospiracea/Clostridium and Lactobacillus families and genera. Members of the avian enteric Reoviridae and Astroviridae have been well-characterized and have historically been implicated in poultry enteric disease; members of the Picobirnaviridae and Picornaviridae have only relatively recently been described in the poultry and avian gut, and their roles in the recognized disease syndromes and in poultry performance in general have not been determined. This metagenomic analysis has provided insight into the colonization of the poultry gut by enteric microbes circulating in commercial broiler flocks, and has identified enteric viruses and virus communities that warrant further study in order to understand their role(s) in avian gut health and disease.",2015 Jan 30,"['Day, J. Michael', 'Oakley, Brian B.', 'Seal, Bruce S.', 'Zsak, Laszlo']",PLoS One,,,True
9bad9c5864165815b35dd2c78cd0ed7b285f0517,PMC,Receptor Binding Domain Based HIV Vaccines,http://dx.doi.org/10.1155/2015/594109,PMC4312573,25667925,CC BY,"This paper analyzes the main trend of the development of acquired immunodeficiency syndrome (AIDS) vaccines in recent years. Designing an HIV-1 vaccine that provides robust protection from HIV-1 infection remains a challenge despite many years of effort. Therefore, we describe the receptor binding domain of gp120 as a target for developing AIDS vaccines. And we recommend some measures that could induce efficiently and produce cross-reactive neutralizing antibodies with high binding affinity. Those measures may offer a new way of the research and development of the potent and broad AIDS vaccines.",2015 Jan 15,"['Liu, Huan', 'Bi, Wenwen', 'Wang, Qian', 'Lu, Lu', 'Jiang, Shibo']",Biomed Res Int,,,True
396b05e6ede13dc6078ddf0eae5c14ceae695600,PMC,Annexin A2 as a target endothelial cell membrane autoantigen in Behçet's disease,http://dx.doi.org/10.1038/srep08162,PMC4313095,25641213,CC BY,"Cell membrane proteins are believed to play a critical role in the pathogenesis of autoimmune diseases. However, few membrane autoantigens have been linked with Behçet's disease. Here, a cell-chip was performed to identify autoantibody target cells, and the suspected autoantigens were detected using immunoblotting. The amino acid sequences of the detected proteins were determined using LC-MALDI-TOF/TOF. Putative proteins were recombinantly expressed and purified, and a corresponding ELISA was developed and clinically validated using real clinical samples. It was found that a 36-kDa membrane protein - annexin A2 - was detected in approximately one-third of the patients' blood circulation. The immunohistochemistry results showed that annexin A2 was highly expressed in vascular endothelial cells. Moreover, vascular involvement was significantly higher in the anti-annexin A2 antibody-positive group versus the anti-annexin A2 antibody-negative group among all the clinical samples analyzed, indicating that annexin A2 is a novel endothelial cell membrane antigen involved in Behçet's disease.",2015 Feb 2,"['Chen, Peng', 'Yan, Hai', 'Tian, Yaping', 'Xun, Yiping', 'Shi, Lili', 'Bao, Ran', 'Zhang, Huai', 'Chen, Guangyu', 'Yang, Chunhe', 'Sun, Shutao', 'Wang, Yajie', 'Liu, Li', 'Zhou, Yabin', 'Zhang, Chunyan', 'Wang, Xiaoxu', 'Wen, Yongqiang', 'Bian, Yongzhong', 'Du, Hongwu']",Sci Rep,,,True
7992401d6ef4c8a20818079438362577895f25b7,PMC,Biosecurity and Dual-Use Research: Gaining Function – But at What Cost?,http://dx.doi.org/10.3389/fpubh.2015.00013,PMC4313596,25699244,CC BY,,2015 Feb 2,"['Vogel, Kathleen M.', 'Ozin, Amanda J.', 'Suk, Jonathan E.']",Front Public Health,,,True
238d2be0d4db41b5460bd3a50a0a374549c189aa,PMC,Houttuynia cordata Targets the Beginning Stage of Herpes Simplex Virus Infection,http://dx.doi.org/10.1371/journal.pone.0115475,PMC4314066,25643242,CC BY,"Herpes simplex virus (HSV), a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV) results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata), a natural herbal medicine, has been reported to exhibit anti-HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs) inhibit the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV.",2015 Feb 2,"['Hung, Pei-Yun', 'Ho, Bing-Ching', 'Lee, Szu-Yuan', 'Chang, Sui-Yuan', 'Kao, Chuan-Liang', 'Lee, Shoei-Sheng', 'Lee, Chun-Nan']",PLoS One,,,True
66309c65612bed65732f79f347693a170e10e1f8,PMC,Angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis prevents lipopolysaccharide–induced apoptosis of pulmonary microvascular endothelial cells by inhibiting JNK/NF–κB pathways,http://dx.doi.org/10.1038/srep08209,PMC4314638,25644821,CC BY,"ACE2 and Ang–(1–7) have important roles in preventing acute lung injury. However, it is not clear whether upregulation of the ACE2/Ang–(1–7)/Mas axis prevents LPS–induced injury in pulmonary microvascular endothelial cells (PMVECs) by inhibiting the MAPKs/NF–κB pathways. Primary cultured rat PMVECs were transduced with lentiviral–borne Ace2 or shRNA–Ace2, and then treated or not with Mas receptor blocker (A779) before exposure to LPS. LPS stimulation resulted in the higher levels of AngII, Ang–(1–7), cytokine secretion, and apoptosis rates, and the lower ACE2/ACE ratio. Ace2 reversed the ACE2/ACE imbalance and increased Ang–(1–7) levels, thus reducing LPS–induced apoptosis and inflammation, while inhibition of Ace2 reversed all these effects. A779 abolished these protective effects of Ace2. LPS treatment was associated with activation of the ERK, p38, JNK, and NF–κB pathways, which were aggravated by A779. Pretreatment with A779 prevented the Ace2–induced blockade of p38, JNK, and NF–κB phosphorylation. However, only JNK inhibitor markedly reduced apoptosis and cytokine secretion in PMVECs with Ace2 deletion and A779 pretreatment. These results suggest that the ACE2/Ang–(1–7)/Mas axis has a crucial role in preventing LPS–induced apoptosis and inflammation of PMVECs, by inhibiting the JNK/NF–κB pathways.",2015 Feb 3,"['Li, Yingchuan', 'Cao, Yongmei', 'Zeng, Zhen', 'Liang, Mengfan', 'Xue, Ying', 'Xi, Caihua', 'Zhou, Ming', 'Jiang, Wei']",Sci Rep,,,True
b4662fd83b035e7eb06014924a4a03c854ad797f,PMC,Exploration of diarrhoea seasonality and its drivers in China,http://dx.doi.org/10.1038/srep08241,PMC4316158,25649629,CC BY,"This study investigated the diarrhoea seasonality and its potential drivers as well as potential opportunities for future diarrhoea control and prevention in China. Data on weekly infectious diarrhoea cases in 31 provinces of China from 2005 to 2012, and data on demographic and geographic characteristics, as well as climatic factors, were complied. A cosinor function combined with a Poisson regression was used to calculate the three seasonal parameters of diarrhoea in different provinces. Regression tree analysis was used to identify the predictors of diarrhoea seasonality. Diarrhoea cases in China showed a bimodal distribution. Diarrhoea in children <5 years was more likely to peak in fall-winter seasons, while diarrhoea in persons > = 5 years peaked in summer. Latitude was significantly associated with spatial pattern of diarrhoea seasonality, with peak and trough times occurring earlier at high latitudes (northern areas), and later at low latitudes (southern areas). The annual amplitudes of diarrhoea in persons > = 5 years increased with latitude (r = 0.62, P<0.001). Latitude 27.8° N and 38.65° N were the latitudinal thresholds for diarrhoea seasonality in China. Regional-specific diarrhoea control and prevention strategies may be optimal for China. More attention should be paid to diarrhoea in children <5 years during fall-winter seasons.",2015 Feb 4,"['Xu, Zhiwei', 'Hu, Wenbiao', 'Zhang, Yewu', 'Wang, Xiaofeng', 'Zhou, Maigeng', 'Su, Hong', 'Huang, Cunrui', 'Tong, Shilu', 'Guo, Qing']",Sci Rep,,,True
6151f96019df6ea8cba1f74c423f9dd6f1e0ec02,PMC,Exploration of diarrhoea seasonality and its drivers in China,http://dx.doi.org/10.1038/srep08241,PMC4316158,25649629,CC BY,"This study investigated the diarrhoea seasonality and its potential drivers as well as potential opportunities for future diarrhoea control and prevention in China. Data on weekly infectious diarrhoea cases in 31 provinces of China from 2005 to 2012, and data on demographic and geographic characteristics, as well as climatic factors, were complied. A cosinor function combined with a Poisson regression was used to calculate the three seasonal parameters of diarrhoea in different provinces. Regression tree analysis was used to identify the predictors of diarrhoea seasonality. Diarrhoea cases in China showed a bimodal distribution. Diarrhoea in children <5 years was more likely to peak in fall-winter seasons, while diarrhoea in persons > = 5 years peaked in summer. Latitude was significantly associated with spatial pattern of diarrhoea seasonality, with peak and trough times occurring earlier at high latitudes (northern areas), and later at low latitudes (southern areas). The annual amplitudes of diarrhoea in persons > = 5 years increased with latitude (r = 0.62, P<0.001). Latitude 27.8° N and 38.65° N were the latitudinal thresholds for diarrhoea seasonality in China. Regional-specific diarrhoea control and prevention strategies may be optimal for China. More attention should be paid to diarrhoea in children <5 years during fall-winter seasons.",2015 Feb 4,"['Xu, Zhiwei', 'Hu, Wenbiao', 'Zhang, Yewu', 'Wang, Xiaofeng', 'Zhou, Maigeng', 'Su, Hong', 'Huang, Cunrui', 'Tong, Shilu', 'Guo, Qing']",Sci Rep,,,False
4c452cc6bb3cb81575f11749b5fb5e5206d6836e,PMC,A confirmed severe case of human infection with avian-origin influenza H7N9: A case report,http://dx.doi.org/10.3892/etm.2014.2159,PMC4316893,25667615,CC BY,"A male patient, aged 77 years, was admitted to hospital with the chief complaint of persistent hyperpyrexia that had presented for four days. The patient also suffered from hypoxemia, and a large white shadow in the left lung was observed on a chest radiograph, indicating inflammation. No therapeutic effect was observed with anti-infection treatment. The patient admitted a history of direct contact with live chickens two weeks prior to hospital admission. The day after admission to the Jingnan District Centre Hospital of Shanghai (Shanghai, China), the patient was diagnosed with severe H7N9 avian influenza infection by nasopharyngeal swab and blood sampling detection. Although the patient received anti-infective drugs, intubated assisted ventilation and circulation support, the condition of the patient continued to rapidly deteriorate. Oxygen saturation decreased and gastrointestinal bleeding occurred, with the body temperature fluctuating between 39 and 40°C. By day 6 after admission, the patient presented with circulatory failure, with liver and renal failure. On day 7, the blood pressure of the patient was unable to be measured, and the patient was diagnosed with multiple organ dysfunction. Subsequently, clinical death was declared with the patient exhibiting asystole and no spontaneous breathing.",2015 Mar 30,"['CAO, HUI-FANG', 'LIANG, ZHONG-HUI', 'FENG, YING', 'ZHANG, ZI-NAN', 'XU, JING', 'HE, HE']",Exp Ther Med,,,True
77888e24fe540edda3d9cd2e0aadd2e699aa466d,PMC,On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events,http://dx.doi.org/10.3389/fimmu.2015.00011,PMC4318428,25699039,CC BY,"Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates.",2015 Feb 5,"['Späth, Peter J.', 'Granata, Guido', 'La Marra, Fabiola', 'Kuijpers, Taco W.', 'Quinti, Isabella']",Front Immunol,,,True
9a31e63c4ec26320695ef383dfd8c772d6afc92b,PMC,Mass fatality preparedness among medical examiners/coroners in the United States: a cross-sectional study,http://dx.doi.org/10.1186/1471-2458-14-1275,PMC4320632,25511819,CC BY,"BACKGROUND: In the United States (US), Medical Examiners and Coroners (ME/Cs) have the legal authority for the management of mass fatality incidents (MFI). Yet, preparedness and operational capabilities in this sector remain largely unknown. The purpose of this study was twofold; first, to identify appropriate measures of preparedness, and second, to assess preparedness levels and factors significantly associated with preparedness. METHODS: Three separate checklists were developed to measure different aspects of preparedness: MFI Plan Elements, Operational Capabilities, and Pre-existing Resource Networks. Using a cross-sectional study design, data on these and other variables of interest were collected in 2014 from a national convenience sample of ME/C using an internet-based, anonymous survey. Preparedness levels were determined and compared across Federal Regions and in relation to the number of Presidential Disaster Declarations, also by Federal Region. Bivariate logistic and multivariable models estimated the associations between organizational characteristics and relative preparedness. RESULTS: A large proportion (42%) of respondents reported that less than 25 additional fatalities over a 48-hour period would exceed their response capacities. The preparedness constructs measured three related, yet distinct, aspects of preparedness, with scores highly variable and generally suboptimal. Median scores for the three preparedness measures also varied across Federal Regions and as compared to the number of Presidential Declared Disasters, also by Federal Region. Capacity was especially limited for activating missing persons call centers, launching public communications, especially via social media, and identifying temporary interment sites. The provision of staff training was the only factor studied that was significantly (positively) associated (p < .05) with all three preparedness measures. Although ME/Cs ranked local partners, such as Offices of Emergency Management, first responders, and funeral homes, as the most important sources of assistance, a sizeable proportion (72%) expected federal assistance. CONCLUSIONS: The three measures of MFI preparedness allowed for a broad and comprehensive assessment of preparedness. In the future, these measures can serve as useful benchmarks or criteria for assessing ME/Cs preparedness. The study findings suggest multiple opportunities for improvement, including the development and implementation of national strategies to ensure uniform standards for MFI management across all jurisdictions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-1275) contains supplementary material, which is available to authorized users.",2014 Dec 15,"['Gershon, Robyn RM', 'Orr, Mark G', 'Zhi, Qi', 'Merrill, Jacqueline A', 'Chen, Daniel Y', 'Riley, Halley EM', 'Sherman, Martin F']",BMC Public Health,,,True
e68bb0f18492dc5645e027d5da3369ed17edbabd,PMC,Mass fatality preparedness among medical examiners/coroners in the United States: a cross-sectional study,http://dx.doi.org/10.1186/1471-2458-14-1275,PMC4320632,25511819,CC BY,"BACKGROUND: In the United States (US), Medical Examiners and Coroners (ME/Cs) have the legal authority for the management of mass fatality incidents (MFI). Yet, preparedness and operational capabilities in this sector remain largely unknown. The purpose of this study was twofold; first, to identify appropriate measures of preparedness, and second, to assess preparedness levels and factors significantly associated with preparedness. METHODS: Three separate checklists were developed to measure different aspects of preparedness: MFI Plan Elements, Operational Capabilities, and Pre-existing Resource Networks. Using a cross-sectional study design, data on these and other variables of interest were collected in 2014 from a national convenience sample of ME/C using an internet-based, anonymous survey. Preparedness levels were determined and compared across Federal Regions and in relation to the number of Presidential Disaster Declarations, also by Federal Region. Bivariate logistic and multivariable models estimated the associations between organizational characteristics and relative preparedness. RESULTS: A large proportion (42%) of respondents reported that less than 25 additional fatalities over a 48-hour period would exceed their response capacities. The preparedness constructs measured three related, yet distinct, aspects of preparedness, with scores highly variable and generally suboptimal. Median scores for the three preparedness measures also varied across Federal Regions and as compared to the number of Presidential Declared Disasters, also by Federal Region. Capacity was especially limited for activating missing persons call centers, launching public communications, especially via social media, and identifying temporary interment sites. The provision of staff training was the only factor studied that was significantly (positively) associated (p < .05) with all three preparedness measures. Although ME/Cs ranked local partners, such as Offices of Emergency Management, first responders, and funeral homes, as the most important sources of assistance, a sizeable proportion (72%) expected federal assistance. CONCLUSIONS: The three measures of MFI preparedness allowed for a broad and comprehensive assessment of preparedness. In the future, these measures can serve as useful benchmarks or criteria for assessing ME/Cs preparedness. The study findings suggest multiple opportunities for improvement, including the development and implementation of national strategies to ensure uniform standards for MFI management across all jurisdictions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-1275) contains supplementary material, which is available to authorized users.",2014 Dec 15,"['Gershon, Robyn RM', 'Orr, Mark G', 'Zhi, Qi', 'Merrill, Jacqueline A', 'Chen, Daniel Y', 'Riley, Halley EM', 'Sherman, Martin F']",BMC Public Health,,,True
f0e6cef57dbae030aea2f324e21e00945ac659cf,PMC,In Vitro Bactericidal Activity of 4- and 5-Chloro-2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides against MRSA,http://dx.doi.org/10.1155/2015/349534,PMC4321674,25692135,CC BY,"A series of nine substituted 2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides was assessed as prospective bactericidal agents against three clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus ATCC 29213 as the reference and quality control strain. The minimum bactericidal concentration was determined by subculturing aliquots from MIC determination onto substance-free agar plates. The bactericidal kinetics of compounds 5-chloro-2-hydroxy-N-[(2S)-3-methyl-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino}butan-2-yl]benzamide (1f), N-{(2S)-1-[(4-bromophenyl)amino]-3-methyl-1-oxobutan-2-yl}-4-chloro-2-hydroxybenzamide (1g), and 4-chloro-N-{(2S)-1-[(3,4-dichlorophenyl)amino]-3-methyl-1-oxobutan-2-yl}-2-hydroxybenzamide (1h) was established by time-kill assay with a final concentration of the compound equal to 1x, 2x, and 4x MIC; aliquots were removed at 0, 4, 6, 8, and 24 h time points. The most potent bactericidal agent was compound 1f exhibiting remarkable rapid concentration-dependent bactericidal effect even at 2x MIC at 4, 6, and 8 h (with a reduction in bacterial count ranging from 3.08 to 3.75 log(10) CFU/mL) and at 4x MIC at 4, 6, 8, and 24 h (5.30 log(10) CFU/mL reduction in bacterial count) after incubation against MRSA 63718. Reliable bactericidal effect against other strains was maintained at 4x MIC at 24 h.",2015 Jan 15,"['Zadrazilova, Iveta', 'Pospisilova, Sarka', 'Pauk, Karel', 'Imramovsky, Ales', 'Vinsova, Jarmila', 'Cizek, Alois', 'Jampilek, Josef']",Biomed Res Int,,,True
77779295f3fcc05a193b349478b8730b226790c7,PMC,"Public, environmental, and occupational health research activity in Arab countries: bibliometric, citation, and collaboration analysis",http://dx.doi.org/10.1186/2049-3258-73-1,PMC4322552,25671116,CC BY,"BACKGROUND: The objective of this study was to analyze quantity, assess quality, and investigate international collaboration in research from Arab countries in the field of public, environmental and occupational health. METHODS: Original scientific articles and reviews published from the 22 Arab countries in the category ""public, environmental & occupational health"" during the study period (1900 – 2012) were screened using the ISI Web of Science database. RESULTS: The total number of original and review research articles published in the category of ""public, environmental & occupational health"" from Arab countries was 4673. Main area of research was tropical medicine (1862; 39.85%). Egypt with 1200 documents (25.86%) ranked first in quantity and ranked first in quality of publications (h-index = 51). The study identified 2036 (43.57%) documents with international collaboration. Arab countries actively collaborated with authors in Western Europe (22.91%) and North America (21.04%). Most of the documents (79.9%) were published in public health related journals while 21% of the documents were published in journals pertaining to prevention medicine, environmental, occupational health and epidemiology. CONCLUSION: Research in public, environmental and occupational health in Arab countries is in the rise. Public health research was dominant while environmental and occupation health research was relatively low. International collaboration was a good tool for increasing research quantity and quality.",2015 Jan 5,"['Sweileh, Waleed M', 'Zyoud, Sa’ed H', 'Al-Jabi, Samah W', 'Sawalha, Ansam F']",Arch Public Health,,,True
bbc0322ac1427ea61ca213645a219daf5bd9d5ac,PMC,Spatial pattern of severe acute respiratory syndrome in-out flow in 2003 in Mainland China,http://dx.doi.org/10.1186/s12879-014-0721-y,PMC4322810,25551367,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS) spread to 32 countries and regions within a few months in 2003. There were 5327 SARS cases from November 2002 to May 2003 in Mainland China, which involved 29 provinces, resulted in 349 deaths, and directly caused economic losses of $18.3 billion. METHODS: This study used an in-out flow model and flow mapping to visualize and explore the spatial pattern of SARS transmission in different regions. In-out flow is measured by the in-out degree and clustering coefficient of SARS. Flow mapping is an exploratory method of spatial visualization for interaction data. RESULTS: The findings were as follows. (1) SARS in-out flow had a clear hierarchy. It formed two main centers, Guangdong in South China and Beijing in North China, and two secondary centers, Shanxi and Inner Mongolia, both connected to Beijing. (2) “Spring Festival travel” strengthened external flow, but “SARS panic effect” played a more significant role and pushed the external flow to the peak. (3) External flow and its three typical kinds showed obvious spatial heterogeneity, such as self-spreading flow (spatial displacement of SARS cases only within the province or municipality of onset and medical locations); hospitalized flow (spatial displacement of SARS cases that had been seen by a hospital doctor); and migrant flow (spatial displacement of SARS cases among migrant workers). (4) Internal and external flow tended to occur in younger groups, and occupational differentiation was particularly evident. Low-income groups of male migrants aged 19–35 years were the main routes of external flow. CONCLUSIONS: During 2002–2003, SARS in-out flow played an important role in countrywide transmission of the disease in Mainland China. The flow had obvious spatial heterogeneity, which was influenced by migrants’ behavior characteristics. In addition, the Chinese holiday effect led to irregular spread of SARS, but the panic effect was more apparent in the middle and late stages of the epidemic. These findings constitute valuable input to prevent and control future serious infectious diseases like SARS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0721-y) contains supplementary material, which is available to authorized users.",2014 Dec 31,"['Xu, Chengdong', 'Wang, Jinfeng', 'Wang, Li', 'Cao, Chunxiang']",BMC Infect Dis,,,True
900c4d81fe0fb7de36ec0235be6e2e873984ec08,PMC,An integrative approach to enhancing small-scale poultry slaughterhouses by addressing regulations and food safety in northern -Thailand,http://dx.doi.org/10.1186/2049-9957-3-46,PMC4322817,25671124,CC BY,"BACKGROUND: In Asian countries, small-scale rural poultry meat production can face challenges due to food safety policies that limit economic growth and hinder improvement of sanitation and disease prevention. In this study, an integrative, participatory research approach was used to elucidate the sanitation and disease prevention practices in small-scale poultry slaughterhouses in rural northern Thailand. METHODS: Initial steps included the identification of key stakeholders associated with the meat production chain, development of a research framework, and design of a methodology based on stakeholder consultations. The framework and methodology combine issues in five major areas: (1) public health, (2) socioeconomics, (3) policy, (4) veterinary medicine, and (5) communities and the environment. Methods used include questionnaires, direct observation, focus groups, and in-depth interviews. In addition, a microbiological risk assessment approach was employed to detect Salmonella contamination in meat processing facilities. The microbial risk assessment was combined with stakeholder perceptions to provide an overview of the existing situation, as well as to identify opportunities for upgrading slaughterhouses in order to more effectively address matters of food safety, processing, and government licensing. RESULTS: The conceptual framework developed elucidated the complex factors limiting small-scale slaughterhouse improvement including a lack of appropriate enabling policies and an apparent absence of feasible interventions for improvement. Unhygienic slaughterhouse management was reflected in the incidence of Salmonella contamination in both the meat and the surrounding environment. CONCLUSION: There is potential for the use of an integrative approach to address critical problems at the interface of rural development and public health. The findings of this study could serve as a model for transdisciplinary studies and interventions related to other similar complex challenges. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-46) contains supplementary material, which is available to authorized users.",2014 Dec 5,"['Chotinun, Suwit', 'Rojanasthien, Suvichai', 'Unger, Fred', 'Suwan, Manat', 'Tadee, Pakpoom', 'Patchanee, Prapas']",Infect Dis Poverty,,,False
41472dcd6a621cee86ccbeedd2fc0f7ae93be71b,PMC,An integrative approach to enhancing small-scale poultry slaughterhouses by addressing regulations and food safety in northern -Thailand,http://dx.doi.org/10.1186/2049-9957-3-46,PMC4322817,25671124,CC BY,"BACKGROUND: In Asian countries, small-scale rural poultry meat production can face challenges due to food safety policies that limit economic growth and hinder improvement of sanitation and disease prevention. In this study, an integrative, participatory research approach was used to elucidate the sanitation and disease prevention practices in small-scale poultry slaughterhouses in rural northern Thailand. METHODS: Initial steps included the identification of key stakeholders associated with the meat production chain, development of a research framework, and design of a methodology based on stakeholder consultations. The framework and methodology combine issues in five major areas: (1) public health, (2) socioeconomics, (3) policy, (4) veterinary medicine, and (5) communities and the environment. Methods used include questionnaires, direct observation, focus groups, and in-depth interviews. In addition, a microbiological risk assessment approach was employed to detect Salmonella contamination in meat processing facilities. The microbial risk assessment was combined with stakeholder perceptions to provide an overview of the existing situation, as well as to identify opportunities for upgrading slaughterhouses in order to more effectively address matters of food safety, processing, and government licensing. RESULTS: The conceptual framework developed elucidated the complex factors limiting small-scale slaughterhouse improvement including a lack of appropriate enabling policies and an apparent absence of feasible interventions for improvement. Unhygienic slaughterhouse management was reflected in the incidence of Salmonella contamination in both the meat and the surrounding environment. CONCLUSION: There is potential for the use of an integrative approach to address critical problems at the interface of rural development and public health. The findings of this study could serve as a model for transdisciplinary studies and interventions related to other similar complex challenges. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-46) contains supplementary material, which is available to authorized users.",2014 Dec 5,"['Chotinun, Suwit', 'Rojanasthien, Suvichai', 'Unger, Fred', 'Suwan, Manat', 'Tadee, Pakpoom', 'Patchanee, Prapas']",Infect Dis Poverty,,,True
7b757b4f7e7148f6899ee9c7ae849ff653471a76,PMC,Generation of Human B-Cell Lines Dependent on CD40-Ligation and Interleukin-4,http://dx.doi.org/10.3389/fimmu.2015.00055,PMC4324153,25717328,CC BY,,2015 Feb 11,"Banchereau, Jacques",Front Immunol,,,True
def339c1e20c36c30ae665e0a4573ed30be45df7,PMC,Nelfinavir Impairs Glycosylation of Herpes Simplex Virus 1 Envelope Proteins and Blocks Virus Maturation,http://dx.doi.org/10.1155/2015/687162,PMC4325974,25709648,CC BY,"Nelfinavir (NFV) is an HIV-1 aspartyl protease inhibitor that has numerous effects on human cells, which impart attractive antitumor properties. NFV has also been shown to have in vitro inhibitory activity against human herpesviruses (HHVs). Given the apparent absence of an aspartyl protease encoded by HHVs, we investigated the mechanism of action of NFV herpes simplex virus type 1 (HSV-1) in cultured cells. Selection of HSV-1 resistance to NFV was not achieved despite multiple passages under drug pressure. NFV did not significantly affect the level of expression of late HSV-1 gene products. Normal numbers of viral particles appeared to be produced in NFV-treated cells by electron microscopy but remain within the cytoplasm more often than controls. NFV did not inhibit the activity of the HSV-1 serine protease nor could its antiviral activity be attributed to inhibition of Akt phosphorylation. NFV was found to decrease glycosylation of viral glycoproteins B and C and resulted in aberrant subcellular localization, consistent with induction of endoplasmic reticulum stress and the unfolded protein response by NFV. These results demonstrate that NFV causes alterations in HSV-1 glycoprotein maturation and egress and likely acts on one or more host cell functions that are important for HHV replication.",2015 Jan 29,"['Gantt, Soren', 'Gachelet, Eliora', 'Carlsson, Jacquelyn', 'Barcy, Serge', 'Casper, Corey', 'Lagunoff, Michael']",Adv Virol,,,True
836ec77a81730c540b750253cc4ee9f8fed0fb49,PMC,Conformational B-Cell Epitope Prediction Method Based on Antigen Preprocessing and Mimotopes Analysis,http://dx.doi.org/10.1155/2015/257030,PMC4326220,25705652,CC BY,"Identification of epitopes which invokes strong humoral responses is an essential issue in the field of immunology. Various computational methods that have been developed based on the antigen structures and the mimotopes these years narrow the search for experimental validation. These methods can be divided into two categories: antigen structure-based methods and mimotope-based methods. Though new methods of the two kinds have been proposed in these years, they cannot maintain a high degree of satisfaction in various circumstances. In this paper, we proposed a new conformational B-cell epitope prediction method based on antigen preprocessing and mimotopes analysis. The method classifies the antigen surface residues into “epitopes” and “nonepitopes” by six epitope propensity scales, removing the “nonepitopes” and using the preprocessed antigen for epitope prediction based on mimotope sequences. The proposed method gives out the mean F score of 0.42 on the testing dataset. When compared with other publicly available servers by using the testing dataset, the new method yields better performance. The results demonstrate the proposed method is competent for the conformational B-cell epitope prediction.",2015 Jan 29,"['Sun, Pingping', 'Ju, Haixu', 'Zhang, Baowen', 'Gu, Yu', 'Liu, Bo', 'Huang, Yanxin', 'Zhang, Huijie', 'Li, Yuxin']",Biomed Res Int,,,True
b86e6acc419df7b1fd637a785834a84b59f4f9c5,PMC,Online health information – what the newspapers tell their readers: a systematic content analysis,http://dx.doi.org/10.1186/1471-2458-14-1316,PMC4326503,25532562,CC BY,"BACKGROUND: This study investigated the nature of newspaper reporting about online health information in the UK and US. Internet users frequently search for health information online, although the accuracy of the information retrieved varies greatly and can be misleading. Newspapers have the potential to influence public health behaviours, but information has been lacking in relation to how newspapers portray online health information to their readers. METHODS: The newspaper database Nexis(®)UK was searched for articles published from 2003 – 2012 relating to online health information. Systematic content analysis of articles published in the highest circulation newspapers in the UK and US was performed. A second researcher coded a 10% sample to establish inter-rater reliability of coding. RESULTS: In total, 161 newspaper articles were included in the analysis. Publication was most frequent in 2003, 2008 and 2009, which coincided with global threats to public health. UK broadsheet newspapers were significantly more likely to cover online health information than UK tabloid newspapers (p = 0.04) and only one article was identified in US tabloid newspapers. Articles most frequently appeared in health sections. Among the 79 articles that linked online health information to specific diseases or health topics, diabetes was the most frequently mentioned disease, cancer the commonest group of diseases and sexual health the most frequent health topic. Articles portrayed benefits of obtaining online health information more frequently than risks. Quotations from health professionals portrayed mixed opinions regarding public access to online health information. 108 (67.1%) articles directed readers to specific health-related web sites. 135 (83.9%) articles were rated as having balanced judgement and 76 (47.2%) were judged as having excellent quality reporting. No difference was found in the quality of reporting between UK and US articles. CONCLUSIONS: Newspaper coverage of online health information was low during the 10-year period 2003 to 2012. Journalists tended to emphasise the benefits and understate the risks of online health information and the quality of reporting varied considerably. Newspapers directed readers to sources of online health information during global epidemics although, as most articles appeared in the health sections of broadsheet newspapers, coverage was limited to a relatively small readership. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-1316) contains supplementary material, which is available to authorized users.",2014 Dec 23,"['McCaw, Brian A', 'McGlade, Kieran J', 'McElnay, James C']",BMC Public Health,,,False
e3c13df830390513f48908347eb132df3f2a773e,PMC,Online health information – what the newspapers tell their readers: a systematic content analysis,http://dx.doi.org/10.1186/1471-2458-14-1316,PMC4326503,25532562,CC BY,"BACKGROUND: This study investigated the nature of newspaper reporting about online health information in the UK and US. Internet users frequently search for health information online, although the accuracy of the information retrieved varies greatly and can be misleading. Newspapers have the potential to influence public health behaviours, but information has been lacking in relation to how newspapers portray online health information to their readers. METHODS: The newspaper database Nexis(®)UK was searched for articles published from 2003 – 2012 relating to online health information. Systematic content analysis of articles published in the highest circulation newspapers in the UK and US was performed. A second researcher coded a 10% sample to establish inter-rater reliability of coding. RESULTS: In total, 161 newspaper articles were included in the analysis. Publication was most frequent in 2003, 2008 and 2009, which coincided with global threats to public health. UK broadsheet newspapers were significantly more likely to cover online health information than UK tabloid newspapers (p = 0.04) and only one article was identified in US tabloid newspapers. Articles most frequently appeared in health sections. Among the 79 articles that linked online health information to specific diseases or health topics, diabetes was the most frequently mentioned disease, cancer the commonest group of diseases and sexual health the most frequent health topic. Articles portrayed benefits of obtaining online health information more frequently than risks. Quotations from health professionals portrayed mixed opinions regarding public access to online health information. 108 (67.1%) articles directed readers to specific health-related web sites. 135 (83.9%) articles were rated as having balanced judgement and 76 (47.2%) were judged as having excellent quality reporting. No difference was found in the quality of reporting between UK and US articles. CONCLUSIONS: Newspaper coverage of online health information was low during the 10-year period 2003 to 2012. Journalists tended to emphasise the benefits and understate the risks of online health information and the quality of reporting varied considerably. Newspapers directed readers to sources of online health information during global epidemics although, as most articles appeared in the health sections of broadsheet newspapers, coverage was limited to a relatively small readership. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-1316) contains supplementary material, which is available to authorized users.",2014 Dec 23,"['McCaw, Brian A', 'McGlade, Kieran J', 'McElnay, James C']",BMC Public Health,,,True
3f94161603e0a339aa90475fe4c7001bb54d1ba7,PMC,Assessment of research productivity of Arab countries in the field of infectious diseases using Web of Science database,http://dx.doi.org/10.1186/2049-9957-4-2,PMC4327970,25685346,CC BY,"BACKGROUND: To meet the future challenges of infectious diseases and limit the spread of multidrug resistant microorganisms, a better understanding of published studies in the field of infectious diseases is needed. The objective of this study was to analyze the quantity and quality of research activity in the field of infectious diseases in Arab countries and compare it with that in non-Arab countries. METHODS: Documents published in Arab countries within the research category of “infectious diseases” were extracted and analyzed using the Web of Science database. The data analyzed represent research productivity during the time interval between 1900 – 2012. RESULTS: Worldwide, the total number of documents published in the field of infectious diseases up to 2012 was 227,188. A total of 2,408 documents in the field of infectious diseases were published in Arab countries, which represents 1.06% of worldwide research output. Research output from Arab countries in the field of infectious diseases was low for decades. However, approximately a five-fold increase was observed in the past decade. Arab countries ranked 56(th) to 218(th) on the standard competition ranking (SCR) in worldwide publications in the field of infectious diseases. Egypt, with a total publication of 464 (19.27%) documents ranked first among Arab countries, while Kuwait University was the most productive institution with a total of 158 (6.56%) documents. Average citation per document published in Arab countries was 13.25 and the h-index was 64. Tuberculosis (230; 9.55%), malaria (223; 9.26%), and hepatitis (189; 7.8%) were the top three infectious diseases studied as according to the retrieved documents. CONCLUSION: The present data reveals that some Arab countries contribute significantly to the field of infectious diseases. However, Arab countries need to work harder to bridge the gap in this field. Compared with non-Arab countries in the Middle East, research output from Arab countries was high, but more efforts are needed to enhance the quality of this output. Future research in the field should be encouraged and correctly directed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-4-2) contains supplementary material, which is available to authorized users.",2015 Feb 2,"['Sweileh, Waleed M', 'Al-Jabi, Samah W', 'Abuzanat, Alaeddin', 'Sawalha, Ansam F', 'AbuTaha, Adham S', 'Ghanim, Mustafa A', 'Zyoud, Sa’ed H']",Infect Dis Poverty,,,False
59acd41ff6a97e730a76fd661b5e10d8cf5290b6,PMC,Assessment of research productivity of Arab countries in the field of infectious diseases using Web of Science database,http://dx.doi.org/10.1186/2049-9957-4-2,PMC4327970,25685346,CC BY,"BACKGROUND: To meet the future challenges of infectious diseases and limit the spread of multidrug resistant microorganisms, a better understanding of published studies in the field of infectious diseases is needed. The objective of this study was to analyze the quantity and quality of research activity in the field of infectious diseases in Arab countries and compare it with that in non-Arab countries. METHODS: Documents published in Arab countries within the research category of “infectious diseases” were extracted and analyzed using the Web of Science database. The data analyzed represent research productivity during the time interval between 1900 – 2012. RESULTS: Worldwide, the total number of documents published in the field of infectious diseases up to 2012 was 227,188. A total of 2,408 documents in the field of infectious diseases were published in Arab countries, which represents 1.06% of worldwide research output. Research output from Arab countries in the field of infectious diseases was low for decades. However, approximately a five-fold increase was observed in the past decade. Arab countries ranked 56(th) to 218(th) on the standard competition ranking (SCR) in worldwide publications in the field of infectious diseases. Egypt, with a total publication of 464 (19.27%) documents ranked first among Arab countries, while Kuwait University was the most productive institution with a total of 158 (6.56%) documents. Average citation per document published in Arab countries was 13.25 and the h-index was 64. Tuberculosis (230; 9.55%), malaria (223; 9.26%), and hepatitis (189; 7.8%) were the top three infectious diseases studied as according to the retrieved documents. CONCLUSION: The present data reveals that some Arab countries contribute significantly to the field of infectious diseases. However, Arab countries need to work harder to bridge the gap in this field. Compared with non-Arab countries in the Middle East, research output from Arab countries was high, but more efforts are needed to enhance the quality of this output. Future research in the field should be encouraged and correctly directed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-4-2) contains supplementary material, which is available to authorized users.",2015 Feb 2,"['Sweileh, Waleed M', 'Al-Jabi, Samah W', 'Abuzanat, Alaeddin', 'Sawalha, Ansam F', 'AbuTaha, Adham S', 'Ghanim, Mustafa A', 'Zyoud, Sa’ed H']",Infect Dis Poverty,,,True
ce8a4f668a135bcd1ff510cef680e548585cef06,PMC,A Serpin Shapes the Extracellular Environment to Prevent Influenza A Virus Maturation,http://dx.doi.org/10.1016/j.cell.2015.01.040,PMC4328142,25679759,CC BY,"Interferon-stimulated genes (ISGs) act in concert to provide a tight barrier against viruses. Recent studies have shed light on the contribution of individual ISG effectors to the antiviral state, but most have examined those acting on early, intracellular stages of the viral life cycle. Here, we applied an image-based screen to identify ISGs inhibiting late stages of influenza A virus (IAV) infection. We unraveled a directly antiviral function for the gene SERPINE1, encoding plasminogen activator inhibitor 1 (PAI-1). By targeting extracellular airway proteases, PAI-1 inhibits IAV glycoprotein cleavage, thereby reducing infectivity of progeny viruses. This was biologically relevant for IAV restriction in vivo. Further, partial PAI-1 deficiency, attributable to a polymorphism in human SERPINE1, conferred increased susceptibility to IAV in vitro. Together, our findings reveal that manipulating the extracellular environment to inhibit the last step in a virus life cycle is an important mechanism of the antiviral response.",2015 Feb 12,"['Dittmann, Meike', 'Hoffmann, Hans-Heinrich', 'Scull, Margaret\xa0A.', 'Gilmore, Rachel\xa0H.', 'Bell, Kierstin\xa0L.', 'Ciancanelli, Michael', 'Wilson, Sam\xa0J.', 'Crotta, Stefania', 'Yu, Yingpu', 'Flatley, Brenna', 'Xiao, Jing\xa0W.', 'Casanova, Jean-Laurent', 'Wack, Andreas', 'Bieniasz, Paul\xa0D.', 'Rice, Charles\xa0M.']",Cell,,,False
fa6fcf0b68fde25abe84c93a517d9965d43c9fbe,PMC,A Serpin Shapes the Extracellular Environment to Prevent Influenza A Virus Maturation,http://dx.doi.org/10.1016/j.cell.2015.01.040,PMC4328142,25679759,CC BY,"Interferon-stimulated genes (ISGs) act in concert to provide a tight barrier against viruses. Recent studies have shed light on the contribution of individual ISG effectors to the antiviral state, but most have examined those acting on early, intracellular stages of the viral life cycle. Here, we applied an image-based screen to identify ISGs inhibiting late stages of influenza A virus (IAV) infection. We unraveled a directly antiviral function for the gene SERPINE1, encoding plasminogen activator inhibitor 1 (PAI-1). By targeting extracellular airway proteases, PAI-1 inhibits IAV glycoprotein cleavage, thereby reducing infectivity of progeny viruses. This was biologically relevant for IAV restriction in vivo. Further, partial PAI-1 deficiency, attributable to a polymorphism in human SERPINE1, conferred increased susceptibility to IAV in vitro. Together, our findings reveal that manipulating the extracellular environment to inhibit the last step in a virus life cycle is an important mechanism of the antiviral response.",2015 Feb 12,"['Dittmann, Meike', 'Hoffmann, Hans-Heinrich', 'Scull, Margaret\xa0A.', 'Gilmore, Rachel\xa0H.', 'Bell, Kierstin\xa0L.', 'Ciancanelli, Michael', 'Wilson, Sam\xa0J.', 'Crotta, Stefania', 'Yu, Yingpu', 'Flatley, Brenna', 'Xiao, Jing\xa0W.', 'Casanova, Jean-Laurent', 'Wack, Andreas', 'Bieniasz, Paul\xa0D.', 'Rice, Charles\xa0M.']",Cell,,,False
164f04163f53a4fb15d74a03b6ab473b50c30989,PMC,Macrophages at the Fork in the Road to Health or Disease,http://dx.doi.org/10.3389/fimmu.2015.00059,PMC4329822,25762997,CC BY,,2015 Feb 16,"['Mills, Charles D.', 'Lenz, Laurel L.', 'Ley, Klaus']",Front Immunol,,,True
6973170d4c8d9576b0e3bfd8391e907d779ee355,PMC,RPI-Pred: predicting ncRNA-protein interaction using sequence and structural information,http://dx.doi.org/10.1093/nar/gkv020,PMC4330382,25609700,CC BY,"RNA-protein complexes are essential in mediating important fundamental cellular processes, such as transport and localization. In particular, ncRNA-protein interactions play an important role in post-transcriptional gene regulation like mRNA localization, mRNA stabilization, poly-adenylation, splicing and translation. The experimental methods to solve RNA-protein interaction prediction problem remain expensive and time-consuming. Here, we present the RPI-Pred (RNA-protein interaction predictor), a new support-vector machine-based method, to predict protein-RNA interaction pairs, based on both the sequences and structures. The results show that RPI-Pred can correctly predict RNA-protein interaction pairs with ∼94% prediction accuracy when using sequence and experimentally determined protein and RNA structures, and with ∼83% when using sequences and predicted protein and RNA structures. Further, our proposed method RPI-Pred was superior to other existing ones by predicting more experimentally validated ncRNA-protein interaction pairs from different organisms. Motivated by the improved performance of RPI-Pred, we further applied our method for reliable construction of ncRNA-protein interaction networks. The RPI-Pred is publicly available at: http://ctsb.is.wfubmc.edu/projects/rpi-pred.",2015 Feb 18,"['Suresh, V.', 'Liu, Liang', 'Adjeroh, Donald', 'Zhou, Xiaobo']",Nucleic Acids Res,,,True
9984fe671d61d99ab39e8e95787e9000093ea7df,PMC,Directed Evolution of a Yeast-Displayed HIV-1 SOSIP gp140 Spike Protein toward Improved Expression and Affinity for Conformational Antibodies,http://dx.doi.org/10.1371/journal.pone.0117227,PMC4331506,25688555,CC BY,"Design of an envelope-based immunogen capable of inducing a broadly neutralizing antibody response is thought to be key to the development of a protective HIV-1 vaccine. However, the broad diversity of viral variants and a limited ability to produce native envelope have hampered such design efforts. Here we describe adaptation of the yeast display system and use of a combinatorial protein engineering approach to permit directed evolution of HIV envelope variants. Because the intrinsic instability and complexity of this trimeric glycoprotein has greatly impeded the development of immunogens that properly represent the structure of native envelope, this platform addresses an essential need for methodologies with the capacity to rapidly engineer HIV spike proteins towards improved homogeneity, stability, and presentation of neutralizing epitopes. We report for the first time the display of a designed SOSIP gp140 on yeast, and the in vitro evolution of derivatives with greatly improved expression and binding to conformation-dependent antibodies. These efforts represent an initial and critical step toward the ability to rapidly engineer HIV-1 envelope immunogens via directed evolution.",2015 Feb 17,"['Grimm, Sebastian K.', 'Battles, Michael B.', 'Ackerman, Margaret E.']",PLoS One,,,True
7e5b5d16ffb537a8e940502af3011d18fe6eff9b,PMC,Genomic Characterization of Novel Circular ssDNA Viruses from Insectivorous Bats in Southern Brazil,http://dx.doi.org/10.1371/journal.pone.0118070,PMC4331541,25688970,CC BY,"Circoviruses are highly prevalent porcine and avian pathogens. In recent years, novel circular ssDNA genomes have recently been detected in a variety of fecal and environmental samples using deep sequencing approaches. In this study the identification of genomes of novel circoviruses and cycloviruses in feces of insectivorous bats is reported. Pan-reactive primers were used targeting the conserved rep region of circoviruses and cycloviruses to screen DNA bat fecal samples. Using this approach, partial rep sequences were detected which formed five phylogenetic groups distributed among the Circovirus and the recently proposed Cyclovirus genera of the Circoviridae. Further analysis using inverse PCR and Sanger sequencing led to the characterization of four new putative members of the family Circoviridae with genome size ranging from 1,608 to 1,790 nt, two inversely arranged ORFs, and canonical nonamer sequences atop a stem loop.",2015 Feb 17,"['Lima, Francisco Esmaile de Sales', 'Cibulski, Samuel Paulo', 'dos Santos, Helton Fernandes', 'Teixeira, Thais Fumaco', 'Varela, Ana Paula Muterle', 'Roehe, Paulo Michel', 'Delwart, Eric', 'Franco, Ana Cláudia']",PLoS One,,,True
8d7f75c01044b85f877a0d1800507cad01edd76b,PMC,Contrasting clinical outcomes in two cohorts of cats naturally infected with feline immunodeficiency virus (FIV),http://dx.doi.org/10.1016/j.vetmic.2014.12.023,PMC4332694,25595267,CC BY,"Despite over 25 years of feline immunodeficiency virus (FIV) research, relatively little is known about the longitudinal course of FIV infection following natural infection. In contrast to published reports of experimental infections using lethal strains of the virus, clinical signs of naturally acquired FIV infection can be mild or inapparent, rather than life-threatening. In this prospective, longitudinal controlled study, based in Chicago, IL (n = 17) and Memphis, TN (n = 27), we investigated two cohorts of privately owned, naturally infected cats kept under different housing conditions. Cats in the Chicago cohort (Group 1) were kept in households of ≤2 cats, while the Memphis cohort (Group 2) comprised part of a large multi-cat household of over 60 cats kept indoors only, with unrestricted access to one another. The majority of cats from Group 1 did not display clinical signs consistent with immunodeficiency during the 22-month observation period. In contrast, the outcome of infection in Group 2 was dramatically different; 17/27 (63%) of cats lost a median of 51.3% of their bodyweight (P < 0.0005) and died during the study period, with lymphoma being the most common cause of mortality. Although the decrease in CD4+ T cell count between enrolment and terminal disease was significant (P = 0.0017), the CD4:CD8 ratio at the time of enrolment did not reliably distinguish FIV-positive cats classified as ‘healthy’ and ‘not healthy’ at either cohort. FIV load at enrolment was significantly lower in Group 1 than in Group 2 (P < 0.0001), but there were no significant differences at enrolment between healthy and not healthy cats at either group. In conclusion, the results of this study suggest that management and housing conditions impact on disease progression and survival times of FIV-positive cats.",2015 Mar 23,"['Bęczkowski, Paweł M.', 'Litster, Annette', 'Lin, Tsang Long', 'Mellor, Dominic J.', 'Willett, Brian J.', 'Hosie, Margaret J.']",Vet Microbiol,,,False
72e37ddb3310bf50385723819244148ab9a787f2,PMC,Comparison of risk factors for seropositivity to feline immunodeficiency virus and feline leukemia virus among cats: a case-case study,http://dx.doi.org/10.1186/s12917-015-0339-3,PMC4332748,25889006,CC BY,"BACKGROUND: Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are reported to have similar risk factors and similar recommendations apply to manage infected cats. However, some contrasting evidence exists in the literature with regard to commonly reported risk factors. In this study, we investigated whether the known risk factors for FIV and FeLV infections have a stronger effect for either infection. This retrospective study included samples from 696 cats seropositive for FIV and 593 cats seropositive for FeLV from the United States and Canada. Data were collected during two cross sectional studies, where cats were tested using IDEXX FIV/FeLV ELISA kits. To compare the effect of known risk factors for FIV infection compared to FeLV, using a case-case study design, random intercept logistic regression models were fit including cats’ age, sex, neuter status, outdoor exposure, health status and type of testing facility as independent variables. A random intercept for testing facility was included to account for clustering expected in testing practices at the individual clinics and shelters. RESULTS: In the multivariable random intercept model, the odds of FIV compared to FeLV positive ELISA results were greater for adults (OR = 2.09, CI: 1.50-2.92), intact males (OR = 3.14, CI: 1.85-3.76), neutered males (OR = 2.68, CI: 1.44- 3.14), cats with outdoor access (OR = 2.58, CI: 1.85-3.76) and lower for cats with clinical illness (OR = 0.60, 95% CI: 0.52-0.90). The variance components obtained from the model indicated clustering at the testing facility level. CONCLUSIONS: Risk factors that have a greater effect on FIV seropositivity include adulthood, being male (neutered or not) and having access to outdoors, while clinical illness was a stronger predictor for FeLV seropositivity. Further studies are warranted to assess the implications of these results for the management and control of these infections.",2015 Feb 10,"['Chhetri, Bimal K', 'Berke, Olaf', 'Pearl, David L', 'Bienzle, Dorothee']",BMC Vet Res,,,True
29c1e7a4bdac021691a22a788312618e8091dd1d,PMC,Acquired immunity and asymptomatic reservoir impact on frontline and airport ebola outbreak syndromic surveillance and response,http://dx.doi.org/10.1186/2049-9957-3-41,PMC4333876,25699182,CC BY,"The number of surveillance networks for infectious disease diagnosis and response has been growing. In 2000, the World Health Organization (WHO) established the Global Outbreak Alert and Response Network, which has been endorsed by each of the 46 WHO African members since then. Yet, taming the dynamics and plague of the vicious Ebola virus disease (EVD) in African countries has been patchy and erratic due to inadequate surveillance and contact tracing, community defiance and resistance, a lack of detection and response systems, meager/weak knowledge and information on the disease, inadequacies in protective materials protocols, contact tracing nightmare and differing priorities at various levels of the public health system. Despite the widespread acceptance of syndromic surveillance (SS) systems, their ability to provide early warning alerts and notifications of outbreaks is still unverified. Information is often too limited for any outbreak, or emerging or otherwise unexpected disease, to be recognized at either the community or the national level. Indeed, little is known about the role and the interactions between the Ebola infection and exposure to other syndemics and the development of acquired immunity, asymptomatic reservoir, and Ebola seroconversion. Can lessons be learnt from smallpox, polio, and influenza immunity, and can immunization against these serve as a guide? In most endemic countries, community health centers and disease control and prevention at airports solely relies on passive routine immunization control and reactive syndromic response. The frontline and airport Ebola SS systems in West Africa have shown deficiencies in terms of responding with an alarming number of case fatalities, and suggest that more detailed insights into Ebola, and proactive actions, are needed. The quest for effective early indicators (EEE) in shifting the public and global health paradigm requires the development and implementation of a comprehensive and effective community or regional integrated pandemic preparedness and surveillance response systems tailored to local contexts. These systems must have mechanisms for early identification, rapid contact tracing and tracking, confirmation, and communication with the local population and the global community, and must endeavor to respond in a timely manner. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-41) contains supplementary material, which is available to authorized users.",2014 Oct 29,"['Tambo, Ernest', 'Xiao-Nong, Zhou']",Infect Dis Poverty,,,False
1378320afa873bdb81e3f3314a430c7a208d2d08,PMC,Acquired immunity and asymptomatic reservoir impact on frontline and airport ebola outbreak syndromic surveillance and response,http://dx.doi.org/10.1186/2049-9957-3-41,PMC4333876,25699182,CC BY,"The number of surveillance networks for infectious disease diagnosis and response has been growing. In 2000, the World Health Organization (WHO) established the Global Outbreak Alert and Response Network, which has been endorsed by each of the 46 WHO African members since then. Yet, taming the dynamics and plague of the vicious Ebola virus disease (EVD) in African countries has been patchy and erratic due to inadequate surveillance and contact tracing, community defiance and resistance, a lack of detection and response systems, meager/weak knowledge and information on the disease, inadequacies in protective materials protocols, contact tracing nightmare and differing priorities at various levels of the public health system. Despite the widespread acceptance of syndromic surveillance (SS) systems, their ability to provide early warning alerts and notifications of outbreaks is still unverified. Information is often too limited for any outbreak, or emerging or otherwise unexpected disease, to be recognized at either the community or the national level. Indeed, little is known about the role and the interactions between the Ebola infection and exposure to other syndemics and the development of acquired immunity, asymptomatic reservoir, and Ebola seroconversion. Can lessons be learnt from smallpox, polio, and influenza immunity, and can immunization against these serve as a guide? In most endemic countries, community health centers and disease control and prevention at airports solely relies on passive routine immunization control and reactive syndromic response. The frontline and airport Ebola SS systems in West Africa have shown deficiencies in terms of responding with an alarming number of case fatalities, and suggest that more detailed insights into Ebola, and proactive actions, are needed. The quest for effective early indicators (EEE) in shifting the public and global health paradigm requires the development and implementation of a comprehensive and effective community or regional integrated pandemic preparedness and surveillance response systems tailored to local contexts. These systems must have mechanisms for early identification, rapid contact tracing and tracking, confirmation, and communication with the local population and the global community, and must endeavor to respond in a timely manner. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-41) contains supplementary material, which is available to authorized users.",2014 Oct 29,"['Tambo, Ernest', 'Xiao-Nong, Zhou']",Infect Dis Poverty,,,True
997f6355fdf8531d31a8bdadd1067f651e2e3d41,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,True
2ebcfe4ce704a545ee3413d526ca0dbfcbd4e0c1,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
7928df13b8fca67fa1de57294cf18ef7ba6fe4e6,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
5e89b0b0edee59ca1455bcec5397470c0782d906,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
7c449ae509e41ecb0d136c30c81522b4331607bc,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
68fb002c1c445d7d6cd0e6c3318ad0d8147c368c,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
97b4c041c80487b86be2c05a2f1cf3c091476aae,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
a5a2639f5ac0a7f972c19a98303418ce6dedeac2,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
dc5b3e87025a1901e5b0691d164ed524544826f8,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
41f4079c64087ea5c19f504cedb17772034bdca4,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
8f4f337cb823896c59091ccefae014e578799656,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
5a446698400926d20afa361f5c96c11495c90cda,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
144707121f348bf956c21693c153a50700222cc9,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
d31e34a1b5d8447f077c8edd36938c68470db017,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
2aa9d8f84bab8eec05bac2a5bb2295ce3b2f9c77,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
fee84e710586ab2a71c3933594cfb6fdba825e43,PMC,Evolution of Genome Size and Complexity in the Rhabdoviridae,http://dx.doi.org/10.1371/journal.ppat.1004664,PMC4334499,25679389,CC BY,"RNA viruses exhibit substantial structural, ecological and genomic diversity. However, genome size in RNA viruses is likely limited by a high mutation rate, resulting in the evolution of various mechanisms to increase complexity while minimising genome expansion. Here we conduct a large-scale analysis of the genome sequences of 99 animal rhabdoviruses, including 45 genomes which we determined de novo, to identify patterns of genome expansion and the evolution of genome complexity. All but seven of the rhabdoviruses clustered into 17 well-supported monophyletic groups, of which eight corresponded to established genera, seven were assigned as new genera, and two were taxonomically ambiguous. We show that the acquisition and loss of new genes appears to have been a central theme of rhabdovirus evolution, and has been associated with the appearance of alternative, overlapping and consecutive ORFs within the major structural protein genes, and the insertion and loss of additional ORFs in each gene junction in a clade-specific manner. Changes in the lengths of gene junctions accounted for as much as 48.5% of the variation in genome size from the smallest to the largest genome, and the frequency with which new ORFs were observed increased in the 3’ to 5’ direction along the genome. We also identify several new families of accessory genes encoded in these regions, and show that non-canonical expression strategies involving TURBS-like termination-reinitiation, ribosomal frame-shifts and leaky ribosomal scanning appear to be common. We conclude that rhabdoviruses have an unusual capacity for genomic plasticity that may be linked to their discontinuous transcription strategy from the negative-sense single-stranded RNA genome, and propose a model that accounts for the regular occurrence of genome expansion and contraction throughout the evolution of the Rhabdoviridae.",2015 Feb 13,"['Walker, Peter J.', 'Firth, Cadhla', 'Widen, Steven G.', 'Blasdell, Kim R.', 'Guzman, Hilda', 'Wood, Thomas G.', 'Paradkar, Prasad N.', 'Holmes, Edward C.', 'Tesh, Robert B.', 'Vasilakis, Nikos']",PLoS Pathog,,,False
188ba8443bebdeaecfda34138ac1afa4736351ba,PMC,Correction: Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner,http://dx.doi.org/10.1371/journal.ppat.1004709,PMC4334521,25679792,CC BY,,2015 Feb 13,,PLoS Pathog,,,False
c6e4261e1a6aa596741c8af357661827bff2c468,PMC,Correction: Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner,http://dx.doi.org/10.1371/journal.ppat.1004709,PMC4334521,25679792,CC BY,,2015 Feb 13,,PLoS Pathog,,,True
3339f4bb346bfa3070ae5fc7dc745ef051535b0e,PMC,Correction: Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner,http://dx.doi.org/10.1371/journal.ppat.1004709,PMC4334521,25679792,CC BY,,2015 Feb 13,,PLoS Pathog,,,True
7e55726d345571690d0e3046664cfac5003c2a89,PMC,Investigating the introduction of porcine epidemic diarrhea virus into an Ohio swine operation,http://dx.doi.org/10.1186/s12917-015-0348-2,PMC4334577,25881144,CC BY,"BACKGROUND: Porcine Epidemic Diarrhea virus (PEDV) is a highly transmissible coronavirus that causes a severe enteric disease that is particularly deadly for neonatal piglets. Since its introduction to the United States in 2013, PEDV has spread quickly across the country and has caused significant financial losses to pork producers. With no fully licensed vaccines currently available in the United States, prevention and control of PEDV disease is heavily reliant on biosecurity measures. Despite proven, effective biosecurity practices, multiple sites and production stages, within and across designated production flows in an Ohio swine operation broke with confirmed PEDV in January 2014, leading the producer and attending veterinarian to investigate the route of introduction. CASE PRESENTATION: On January 12, 2014, several sows within a production flow were noted with signs of enteric illness. Within a few days, illness had spread to most of the sows in the facility and was confirmed by RT-PCR to be PEDV. Within a short time period, confirmed disease was present on multiple sites within and across breeding and post weaning production flows of the operation and mortality approached 100% in neonatal piglets. After an epidemiologic investigation, an outsourced, pelleted piglet diet was identified for assessment, and a bioassay, where naïve piglets were fed the suspected feed pellets, was initiated to test the pellets for infectious PEDV. CONCLUSIONS: The epidemiological investigation provided strong evidence for contaminated feed as the source of the outbreak. In addition, feed pellets collected from unopened bags at the affected sites tested positive for PEDV using RT-PCR. However, the bioassay study was not able to show infectivity when feeding the suspected feed pellets to a small number of naïve piglets. The results highlight the critical need for surveillance of feed and feed components to further define transmission avenues in an effort to limit the spread of PEDV throughout the U.S. swine industry.",2015 Feb 15,"['Bowman, Andrew S', 'Krogwold, Roger A', 'Price, Todd', 'Davis, Matt', 'Moeller, Steven J']",BMC Vet Res,,,True
5f83e9b8450e30448ab3c65807f414013a12d179,PMC,Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus,http://dx.doi.org/10.1186/2049-9957-3-43,PMC4334593,25699183,CC BY,"The recent outbreak of the human Zaire ebolavirus (EBOV) epidemic is spiraling out of control in West Africa. Human EBOV hemorrhagic fever has a case fatality rate of up to 90%. The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention, with no approved therapies and vaccines available for its treatment apart from supportive care. Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial, the current epidemic might be outpacing the speed at which drugs and vaccines can be produced. Like all viruses, the EBOV largely relies on host cell factors and physiological processes for its entry, replication, and egress. We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies. Most of the therapeutic agents in this review are directed against non-mutable targets of the host, which is independent of viral mutation. These medications are approved by the Food and Drug Administration (FDA) for the treatment of other diseases. They are available and stockpileable for immediate use. They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-43) contains supplementary material, which is available to authorized users.",2014 Nov 28,"['Lai, Kang Yiu', 'Ng, Wing Yiu George', 'Cheng, Fan Fanny']",Infect Dis Poverty,,,False
06190bfcbc53a5d5d17e0a60a3a0f6488d8ae1db,PMC,Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus,http://dx.doi.org/10.1186/2049-9957-3-43,PMC4334593,25699183,CC BY,"The recent outbreak of the human Zaire ebolavirus (EBOV) epidemic is spiraling out of control in West Africa. Human EBOV hemorrhagic fever has a case fatality rate of up to 90%. The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention, with no approved therapies and vaccines available for its treatment apart from supportive care. Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial, the current epidemic might be outpacing the speed at which drugs and vaccines can be produced. Like all viruses, the EBOV largely relies on host cell factors and physiological processes for its entry, replication, and egress. We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies. Most of the therapeutic agents in this review are directed against non-mutable targets of the host, which is independent of viral mutation. These medications are approved by the Food and Drug Administration (FDA) for the treatment of other diseases. They are available and stockpileable for immediate use. They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-43) contains supplementary material, which is available to authorized users.",2014 Nov 28,"['Lai, Kang Yiu', 'Ng, Wing Yiu George', 'Cheng, Fan Fanny']",Infect Dis Poverty,,,True
a4cfc3e2cc8c3a69d8a6384aa77b9a9ff7a51dd7,PMC,Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation,http://dx.doi.org/10.1371/journal.ppat.1004649,PMC4335073,25695775,CC BY,"The rising prevalence of arthritogenic alphavirus infections, including chikungunya virus (CHIKV) and Ross River virus (RRV), and the lack of antiviral treatments highlight the potential threat of a global alphavirus pandemic. The immune responses underlying alphavirus virulence remain enigmatic. We found that pentraxin 3 (PTX3) was highly expressed in CHIKV and RRV patients during acute disease. Overt expression of PTX3 in CHIKV patients was associated with increased viral load and disease severity. PTX3-deficient (PTX3(-/-)) mice acutely infected with RRV exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication. Furthermore, binding of the N-terminal domain of PTX3 to RRV facilitated viral entry and replication. Thus, our study demonstrates the pivotal role of PTX3 in shaping alphavirus-triggered immunity and disease and provides new insights into alphavirus pathogenesis.",2015 Feb 19,"['Foo, Suan-Sin', 'Chen, Weiqiang', 'Taylor, Adam', 'Sheng, Kuo-Ching', 'Yu, Xing', 'Teng, Terk-Shin', 'Reading, Patrick C.', 'Blanchard, Helen', 'Garlanda, Cecilia', 'Mantovani, Alberto', 'Ng, Lisa F. P.', 'Herrero, Lara J.', 'Mahalingam, Suresh']",PLoS Pathog,,,True
1e1f8ec1fffc3e243c9c5b53baf146f0e7c6ddb0,PMC,Murine Norovirus 1 (MNV1) Replication Induces Translational Control of the Host by Regulating eIF4E Activity during Infection,http://dx.doi.org/10.1074/jbc.M114.602649,PMC4335213,25561727,CC BY,"Protein synthesis is a tightly controlled process responding to several stimuli, including viral infection. As obligate intracellular parasites, viruses depend on the translation machinery of the host and can manipulate it by affecting the availability and function of specific eukaryotic initiation factors (eIFs). Human norovirus is a member of the Caliciviridae family and is responsible for gastroenteritis outbreaks. Previous studies on feline calicivirus and murine norovirus 1 (MNV1) demonstrated that the viral protein, genome-linked (VPg), acts to direct translation by hijacking the host protein synthesis machinery. Here we report that MNV1 infection modulates the MAPK pathway to activate eIF4E phosphorylation. Our results show that the activation of p38 and Mnk during MNV1 infection is important for MNV1 replication. Furthermore, phosphorylated eIF4E relocates to the polysomes, and this contributes to changes in the translational state of specific host mRNAs. We propose that global translational control of the host by eIF4E phosphorylation is a key component of the host-pathogen interaction.",2015 Feb 20,"['Royall, Elizabeth', 'Doyle, Nicole', 'Abdul-Wahab, Azimah', 'Emmott, Ed', 'Morley, Simon J.', 'Goodfellow, Ian', 'Roberts, Lisa O.', 'Locker, Nicolas']",J Biol Chem,,,True
433cb6b526e64343c82717d42daab33b2379f252,PMC,Small molecules with antiviral activity against the Ebola virus,http://dx.doi.org/10.12688/f1000research.6120.1,PMC4335594,25713700,CC BY,"The recent outbreak of the Ebola virus in West Africa has highlighted the clear shortage of broad-spectrum antiviral drugs for emerging viruses. There are numerous FDA approved drugs and other small molecules described in the literature that could be further evaluated for their potential as antiviral compounds. These molecules are in addition to the few new antivirals that have been tested in Ebola patients but were not originally developed against the Ebola virus, and may play an important role as we await an effective vaccine. The balance between using FDA approved drugs versus novel antivirals with minimal safety and no efficacy data in humans should be considered. We have evaluated 55 molecules from the perspective of an experienced medicinal chemist as well as using simple molecular properties and have highlighted 16 compounds that have desirable qualities as well as those that may be less desirable. In addition we propose that a collaborative database for sharing such published and novel information on small molecules is needed for the research community studying the Ebola virus.",2015 Feb 9,"['Litterman, Nadia', 'Lipinski, Christopher', 'Ekins, Sean']",F1000Res,,,True
3c8f08f49903aa46c23718a59a6bb221879aa1d2,PMC,The Nucleocapsid Protein of Human Coronavirus NL63,http://dx.doi.org/10.1371/journal.pone.0117833,PMC4336326,25700263,CC0,"Human coronavirus (HCoV) NL63 was first described in 2004 and is associated with respiratory tract disease of varying severity. At the genetic and structural level, HCoV-NL63 is similar to other members of the Coronavirinae subfamily, especially human coronavirus 229E (HCoV-229E). Detailed analysis, however, reveals several unique features of the pathogen. The coronaviral nucleocapsid protein is abundantly present in infected cells. It is a multi-domain, multi-functional protein important for viral replication and a number of cellular processes. The aim of the present study was to characterize the HCoV-NL63 nucleocapsid protein. Biochemical analyses revealed that the protein shares characteristics with homologous proteins encoded in other coronaviral genomes, with the N-terminal domain responsible for nucleic acid binding and the C-terminal domain involved in protein oligomerization. Surprisingly, analysis of the subcellular localization of the N protein of HCoV-NL63 revealed that, differently than homologous proteins from other coronaviral species except for SARS-CoV, it is not present in the nucleus of infected or transfected cells. Furthermore, no significant alteration in cell cycle progression in cells expressing the protein was observed. This is in stark contrast with results obtained for other coronaviruses, except for the SARS-CoV.",2015 Feb 20,"['Zuwała, Kaja', 'Golda, Anna', 'Kabala, Wojciech', 'Burmistrz, Michał', 'Zdzalik, Michal', 'Nowak, Paulina', 'Kedracka-Krok, Sylwia', 'Zarebski, Mirosław', 'Dobrucki, Jerzy', 'Florek, Dominik', 'Zeglen, Sławomir', 'Wojarski, Jacek', 'Potempa, Jan', 'Dubin, Grzegorz', 'Pyrc, Krzysztof']",PLoS One,,,True
0ce0b8bb68417974932e98c094ec93fbefc5193b,PMC,Targeting interferon response genes sensitizes aromatase inhibitor resistant breast cancer cells to estrogen-induced cell death,http://dx.doi.org/10.1186/s13058-014-0506-7,PMC4336497,25588716,CC BY,"INTRODUCTION: Estrogen deprivation using aromatase inhibitors (AIs) is currently the standard of care for postmenopausal women with hormone receptor-positive breast cancer. Unfortunately, the majority of patients treated with AIs eventually develop resistance, inevitably resulting in patient relapse and, ultimately, death. The mechanism by which resistance occurs is still not completely known, however, recent studies suggest that impaired/defective interferon signaling might play a role. In the present study, we assessed the functional role of IFITM1 and PLSCR1; two well-known interferon response genes in AI resistance. METHODS: Real-time PCR and Western blot analyses were used to assess mRNA and protein levels of IFITM1, PLSCR1, STAT1, STAT2, and IRF-7 in AI-resistant MCF-7:5C breast cancer cells and AI-sensitive MCF-7 and T47D cells. Immunohistochemistry (IHC) staining was performed on tissue microarrays consisting of normal breast tissues, primary breast tumors, and AI-resistant recurrence tumors. Enzyme-linked immunosorbent assay was used to quantitate intracellular IFNα level. Neutralizing antibody was used to block type 1 interferon receptor IFNAR1 signaling. Small interference RNA (siRNA) was used to knockdown IFITM1, PLSCR1, STAT1, STAT2, IRF-7, and IFNα expression. RESULTS: We found that IFITM1 and PLSCR1 were constitutively overexpressed in AI-resistant MCF-7:5C breast cancer cells and AI-resistant tumors and that siRNA knockdown of IFITM1 significantly inhibited the ability of the resistant cells to proliferate, migrate, and invade. Interestingly, suppression of IFITM1 significantly enhanced estradiol-induced cell death in AI-resistant MCF-7:5C cells and markedly increased expression of p21, Bax, and Noxa in these cells. Significantly elevated level of IFNα was detected in AI-resistant MCF-7:5C cells compared to parental MCF-7 cells and suppression of IFNα dramatically reduced IFITM1, PLSCR1, p-STAT1, and p-STAT2 expression in the resistant cells. Lastly, neutralizing antibody against IFNAR1/2 and knockdown of STAT1/STAT2 completely suppressed IFITM1, PLSCR1, p-STAT1, and p-STAT2 expression in the resistant cells, thus confirming the involvement of the canonical IFNα signaling pathway in driving the overexpression of IFITM1 and other interferon-stimulated genes (ISGs) in the resistant cells. CONCLUSION: Overall, these results demonstrate that constitutive overexpression of ISGs enhances the progression of AI-resistant breast cancer and that suppression of IFITM1 and other ISGs sensitizes AI-resistant cells to estrogen-induced cell death. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-014-0506-7) contains supplementary material, which is available to authorized users.",2015 Jan 15,"['Choi, Hye Joung', 'Lui, Asona', 'Ogony, Joshua', 'Jan, Rifat', 'Sims, Peter J', 'Lewis-Wambi, Joan']",Breast Cancer Res,,,True
684a0a1db464c0c6e1571a6ca9ea5d2003f62456,PMC,Aberrant expression of long noncoding RNAs in chronic thromboembolic pulmonary hypertension,http://dx.doi.org/10.3892/mmr.2014.3102,PMC4337719,25522749,CC BY,"Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the primary causes of severe pulmonary hypertension. In order to identify long noncoding RNAs (lncRNAs) that may be involved in the development of CTEPH, comprehensive lncRNA and messenger RNA (mRNA) profiling of endothelial tissues from the pulmonary arteries of CTEPH patients was conducted with microarray analysis. Differential expression of 185 lncRNAs was observed in the CTEPH tissues compared with healthy control tissues. Further analysis identified 464 regulated enhancer-like lncRNAs and overlapping, antisense or nearby mRNA pairs. Coexpression networks were subsequently constructed and investigated. The expression levels of the lncRNAs, NR_036693, NR_027783, NR_033766 and NR_001284, were significantly altered. Gene ontology and pathway analysis demonstrated the potential role of lncRNAs in the regulation of central process, including inflammatory response, response to endogenous stimulus and antigen processing and presentation. The use of bioinformatics may help to uncover and analyze large quantities of data identified by microarray analyses, through rigorous experimental planning, statistical analysis and the collection of more comprehensive data regarding CTEPH. The results of the present study provided evidence which may be helpful in future studies on the diagnosis and management of CTEPH.",2015 Apr 17,"['GU, SONG', 'LI, GUANGHUI', 'ZHANG, XITAO', 'YAN, JUN', 'GAO, JIE', 'AN, XIANGGUANG', 'LIU, YAN', 'SU, PIXIONG']",Mol Med Rep,,,True
bb8a9e29bc65471177f470285c32d879c2cb7263,PMC,Effectiveness of traveller screening for emerging pathogens is shaped by epidemiology and natural history of infection,http://dx.doi.org/10.7554/eLife.05564,PMC4337724,25695520,CC BY,"During outbreaks of high-consequence pathogens, airport screening programs have been deployed to curtail geographic spread of infection. The effectiveness of screening depends on several factors, including pathogen natural history and epidemiology, human behavior, and characteristics of the source epidemic. We developed a mathematical model to understand how these factors combine to influence screening outcomes. We analyzed screening programs for six emerging pathogens in the early and late stages of an epidemic. We show that the effectiveness of different screening tools depends strongly on pathogen natural history and epidemiological features, as well as human factors in implementation and compliance. For pathogens with longer incubation periods, exposure risk detection dominates in growing epidemics, while fever becomes a better target in stable or declining epidemics. For pathogens with short incubation, fever screening drives detection in any epidemic stage. However, even in the most optimistic scenario arrival screening will miss the majority of cases. DOI: http://dx.doi.org/10.7554/eLife.05564.001",,"['Gostic, Katelyn M', 'Kucharski, Adam J', 'Lloyd-Smith, James O']",eLife.; 4:e05564,,,True
3118aa53f6b7e539049e2a52e973f4124ba121e9,PMC,First Discovery of Acetone Extract from Cottonseed Oil Sludge as a Novel Antiviral Agent against Plant Viruses,http://dx.doi.org/10.1371/journal.pone.0117496,PMC4337905,25705894,CC BY,"A novel acetone extract from cottonseed oil sludge was firstly discovered against plant viruses including Tobacco mosaic virus (TMV), Rice stripe virus (RSV) and Southern rice black streaked dwarf virus (SRBSDV). Gossypol and β-sitosterol separated from the acetone extract were tested for their effects on anti-TMV and analysed by nuclear magnetic resonance (NMR) assay. In vivo and field trials in different geographic distributions and different host varieties declared that this extract mixture was more efficient than the commercial agent Ningnanmycin with a broad spectrum of anti-plant-viruses activity. No phytotoxic activity was observed in the treated plants and environmental toxicology showed that this new acetone extract was environmentally friendly, indicating that this acetone extract has potential application in the control of plant virus in the future.",2015 Feb 23,"['Zhao, Lei', 'Feng, Chaohong', 'Hou, Caiting', 'Hu, Lingyun', 'Wang, Qiaochun', 'Wu, Yunfeng']",PLoS One,,,True
b4e24eaf67301135a909892450e011eaaa27f780,PMC,Analysis of Cathepsin and Furin Proteolytic Enzymes Involved in Viral Fusion Protein Activation in Cells of the Bat Reservoir Host,http://dx.doi.org/10.1371/journal.pone.0115736,PMC4338073,25706132,CC BY,"Bats of different species play a major role in the emergence and transmission of highly pathogenic viruses including Ebola virus, SARS-like coronavirus and the henipaviruses. These viruses require proteolytic activation of surface envelope glycoproteins needed for entry, and cellular cathepsins have been shown to be involved in proteolysis of glycoproteins from these distinct virus families. Very little is currently known about the available proteases in bats. To determine whether the utilization of cathepsins by bat-borne viruses is related to the nature of proteases in their natural hosts, we examined proteolytic processing of several viral fusion proteins in cells derived from two fruit bat species, Pteropus alecto and Rousettus aegyptiacus. Our work shows that fruit bat cells have homologs of cathepsin and furin proteases capable of cleaving and activating both the cathepsin-dependent Hendra virus F and the furin-dependent parainfluenza virus 5 F proteins. Sequence analysis comparing Pteropus alecto furin and cathepsin L to proteases from other mammalian species showed a high degree of conservation; however significant amino acid variation occurs at the C-terminus of Pteropus alecto furin. Further analysis of furin-like proteases from fruit bats revealed that these proteases are catalytically active and resemble other mammalian furins in their response to a potent furin inhibitor. However, kinetic analysis suggests that differences may exist in the cellular localization of furin between different species. Collectively, these results indicate that the unusual role of cathepsin proteases in the life cycle of bat-borne viruses is not due to the lack of active furin-like proteases in these natural reservoir species; however, differences may exist between furin proteases present in fruit bats compared to furins in other mammalian species, and these differences may impact protease usage for viral glycoprotein processing.",2015 Feb 23,"['El Najjar, Farah', 'Lampe, Levi', 'Baker, Michelle L.', 'Wang, Lin-Fa', 'Dutch, Rebecca Ellis']",PLoS One,,,True
d17a83f05547d542975169b6d43912eae3afd17b,PMC,Structural analysis of herpes simplex virus by optical super-resolution imaging,http://dx.doi.org/10.1038/ncomms6980,PMC4338551,25609143,CC BY,"Herpes simplex virus type-1 (HSV-1) is one of the most widespread pathogens among humans. Although the structure of HSV-1 has been extensively investigated, the precise organization of tegument and envelope proteins remains elusive. Here we use super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) in combination with a model-based analysis of single-molecule localization data, to determine the position of protein layers within virus particles. We resolve different protein layers within individual HSV-1 particles using multi-colour dSTORM imaging and discriminate envelope-anchored glycoproteins from tegument proteins, both in purified virions and in virions present in infected cells. Precise characterization of HSV-1 structure was achieved by particle averaging of purified viruses and model-based analysis of the radial distribution of the tegument proteins VP16, VP1/2 and pUL37, and envelope protein gD. From this data, we propose a model of the protein organization inside the tegument.",2015 Jan 22,"['Laine, Romain F.', 'Albecka, Anna', 'van de Linde, Sebastian', 'Rees, Eric J.', 'Crump, Colin M.', 'Kaminski, Clemens F.']",Nat Commun,,,True
73b5a68dd7e80ad291c026145c875eb8338daa08,PMC,Structural analysis of herpes simplex virus by optical super-resolution imaging,http://dx.doi.org/10.1038/ncomms6980,PMC4338551,25609143,CC BY,"Herpes simplex virus type-1 (HSV-1) is one of the most widespread pathogens among humans. Although the structure of HSV-1 has been extensively investigated, the precise organization of tegument and envelope proteins remains elusive. Here we use super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) in combination with a model-based analysis of single-molecule localization data, to determine the position of protein layers within virus particles. We resolve different protein layers within individual HSV-1 particles using multi-colour dSTORM imaging and discriminate envelope-anchored glycoproteins from tegument proteins, both in purified virions and in virions present in infected cells. Precise characterization of HSV-1 structure was achieved by particle averaging of purified viruses and model-based analysis of the radial distribution of the tegument proteins VP16, VP1/2 and pUL37, and envelope protein gD. From this data, we propose a model of the protein organization inside the tegument.",2015 Jan 22,"['Laine, Romain F.', 'Albecka, Anna', 'van de Linde, Sebastian', 'Rees, Eric J.', 'Crump, Colin M.', 'Kaminski, Clemens F.']",Nat Commun,,,True
c13377750d32446f66a4bcd0bb2da626e4b2a035,PMC,Pilgrims and MERS-CoV: what’s the risk?,http://dx.doi.org/10.1186/s12982-015-0025-8,PMC4339294,25717340,CC BY,"The risk of Middle East Respiratory Syndrome Coronavirus spreading globally is worrying, given the annual mass gathering of the Hajj and the year-long influx of pilgrims undertaking the Umrah. Based on the incidence in Saudi Arabia since June 2012, the most likely scenario given recent pilgrim numbers is estimated to be one case per Hajj, and three Umrah pilgrims per year, but which could plausibly reach seven and ten pilgrims respectively. In addition to the 2015 Hajj, national surveillance systems should be on the alert for the low but long-lasting risk of infected pilgrims returning from the Umrah throughout the year.",2015 Feb 18,"['Soliman, Tarek', 'Cook, Alex R', 'Coker, Richard J']",Emerg Themes Epidemiol,,,True
a4d06a5b2f6f7b1071b36b9ba083e757d0f4ec97,PMC,Humanitarian Access to Unapproved Interventions in Public Health Emergencies of International Concern,http://dx.doi.org/10.1371/journal.pmed.1001793,PMC4339858,25710504,CC BY,Jerome Singh considers how regulatory mechanisms can allow access to experimental interventions in humanitarian emergencies such as the Ebola epidemic.,2015 Feb 24,"Singh, Jerome Amir",PLoS Med,,,True
360a370b63f370b54fa937b5ca0078606acaf805,PMC,Tough challenges for testing Ebola therapeutics,http://dx.doi.org/10.2471/BLT.15.020215,PMC4339970,25883398,CC BY,"Therapies for Ebola virus disease are urgently needed, but they must be rigorously tested for safety and efficacy before any mass roll-out to patients. Fiona Fleck reports.",2015 Feb 1,,Bull World Health Organ,,,False
917928bee48f4118e1f14349d4176df8281e9cac,PMC,Diffuse parenchymal lung disease as first clinical manifestation of GATA-2 deficiency in childhood,http://dx.doi.org/10.1186/s12890-015-0006-2,PMC4340788,25879889,CC BY,"BACKGROUND: GATA-2 transcription factor deficiency has recently been described in patients with a propensity towards myeloid malignancy associated with other highly variable phenotypic features: chronic leukocytopenias (dendritic cell-, monocyto-, granulocyto-, lymphocytopenia), increased susceptibility to infections, lymphatic vasculature abnormalities, and sensorineural deafness. Patients often suffer from opportunistic respiratory infections; chronic pulmonary changes have been found in advanced disease. CASE PRESENTATION: We present a case of a 17-year-old previously healthy Caucasian male who was admitted to the hospital with fever, malaise, headache, cough and dyspnea. A chest X-ray revealed bilateral interstitial infiltrates and pneumonia was diagnosed. Despite prompt clinical improvement under antibiotic therapy, interstitial changes remained stable. A high resolution computer tomography showed severe diffuse parenchymal lung disease, while the patient’s pulmonary function tests were normal and he was asymptomatic. Lung tissue biopsy revealed chronic reparative and resorptive reaction with organizing vasculitis. At the time of the initial presentation to the hospital, serological signs of acute infection with Epstein-Barr virus (EBV) were present; EBV viremia with atypical serological response persisted during two-year follow up. No other infectious agents were found. Marked monocytopenia combined with B-cell lymphopenia led to a suspicion of GATA-2 deficiency. Diagnosis was confirmed by detection of the previously published heterozygous mutation in GATA2 (c.1081 C > T, p.R361C). The patient’s brother and father were both carriers of the same genetic defect. The brother had no clinically relevant ailments despite leukocyte changes similar to the index patient. The father suffered from spondylarthritis, and apart from B-cell lymphopenia, no other changes within the leukocyte pool were seen. CONCLUSION: We conclude that a diagnosis of GATA-2 deficiency should be considered in all patients with diffuse parenchymal lung disease presenting together with leukocytopenia, namely monocyto-, dendritic cell- and B-lymphopenia, irrespective of severity of the clinical phenotype. Genetic counseling and screening for GATA2 mutations within the patient’s family should be provided as the phenotype is highly variable and carriers without apparent immunodeficiency are still in danger of developing myeloid malignancy. A prompt recognition of this rare condition helps to direct clinical treatment strategies and follow-up procedures.",2015 Feb 10,"['Svobodova, Tamara', 'Mejstrikova, Ester', 'Salzer, Ulrich', 'Sukova, Martina', 'Hubacek, Petr', 'Matej, Radoslav', 'Vasakova, Martina', 'Hornofova, Ludmila', 'Dvorakova, Marcela', 'Fronkova, Eva', 'Votava, Felix', 'Freiberger, Tomas', 'Pohunek, Petr', 'Stary, Jan', 'Janda, Ales']",BMC Pulm Med,,,True
7cdb43f29cfdaaa897797a4dfddb41de79b23287,PMC,Emerging and re-emerging infectious diseases: challenges and opportunities for militaries,http://dx.doi.org/10.1186/2054-9369-1-21,PMC4341224,25722877,CC BY,"The communal nature of living and training environments, alongside suboptimal hygiene and stressors in the field, place military personnel at higher risk of contracting emerging infectious diseases. Some of these diseases spread quickly within ranks resulting in large outbreaks, and personnel deployed are also often immunologically naïve to otherwise uncommonly-encountered pathogens. Furthermore, the chance of weaponised biological agents being used in conventional warfare or otherwise remains a very real, albeit often veiled, threat. However, such challenges also provide opportunities for the advancement of preventive and therapeutic military medicine, some of which have been later adopted in civilian settings. Some of these include improved surveillance, new vaccines and drugs, better public health interventions and inter-agency co-operations. The legacy of successes in dealing with infectious diseases is a reminder of the importance in sustaining efforts aimed at ensuring a safer environment for both military and the community at large.",2014 Sep 24,"['Ho, Zheng Jie Marc', 'Hwang, Yi Fu Jeff', 'Lee, Jian Ming Vernon']",Mil Med Res,,,True
9c7ef724d9e2d25e32eceb1ed8a9fe417fe32309,PMC,Effects of Storage Time on Total Protein and Globulin Concentrations in Bovine Fresh Frozen Plasma Obtained for Transfusion,http://dx.doi.org/10.1155/2015/752724,PMC4342078,25767825,CC BY,"To evaluate the effects of storage conditions on total protein (TP) and globulin fractions in fresh frozen bovine plasma units prepared and stored for transfusion, TP and globulin fractions were evaluated in fresh plasma and at 1 month and 6 and 12 months after blood collection in plasma stored at −20°C. Significant differences in concentrations were found in the median concentration of total protein (P = 0.0336), between 0 months and 1 month (P = 0.0108), 0 and 6 months (P = 0.0023), and 0 and 12 months (P = 0.0027), in mean concentration (g/dL) of albumin (P = 0.0394), between 0 months and 1 month (P = 0.0131), 0 and 6 months (P = 0.0035), and 0 and 12 months (P = 0.0038), and beta-2 fraction (P = 0.0401), between 0 and 6 months (P = 0.0401) and 0 and 12 months (P = 0.0230). This study suggests that total gamma globulin concentration in bovine frozen plasma is stable for 12 months at −20°C. Total protein, ALB, and beta-2 fraction have significantly different concentrations (g/dL) when compared to prestorage. This study has shown IgG protein fraction stability in bovine fresh frozen plasma collected for transfusion; therefore, bovine fresh frozen plasma seems to be suitable for the treatment of hypogammaglobulinemia (failure of passive transfer) in calves when stored for 12 months at −20°C.",2015 Feb 12,"['Proverbio, D.', 'Spada, E.', 'Baggiani, L.', 'Bagnagatti De Giorgi, G.', 'Roggero, N.', 'Belloli, A.', 'Pravettoni, D.', 'Perego, R.']",ScientificWorldJournal,,,True
facba90187f6bee3be651d71fc54a715055eaa1d,PMC,Viral etiology of community-acquired pneumonia among adolescents and adults with mild or moderate severity and its relation to age and severity,http://dx.doi.org/10.1186/s12879-015-0808-0,PMC4342096,25812108,CC BY,"BACKGROUND: Better knowledge of distribution of respiratory viruses (RVs) in adolescents and adults with community-acquired pneumonia (CAP) is needed. METHODS: To investigate the RVs etiology among adolescents and adults with CAP, according to age and pneumonia severity index (PSI), a multi-center, prospective study was conducted from November 2010 to April 2012. Fifteen RVs were tested by polymerase chain reaction (PCR). Bacteria were detected by urinary antigen, conventional culture and PCR. RESULTS: Mean (SD) age and median (IQR) PSI score of 954 patients enrolled was 45.2 (19.5) years (range 14–94) and 42 (36). RVs were found in 262 patients (27.5%): influenza virus A (IFV A, 9.9%) comprised of pandemic H1N1 (6.7%) and seasonal H3N2 (3.5%), human rhinovirus (4.3%), adenovirus (4.2%), human metapneumovirus (1.8%), parainfluenza virus 1, 3 and 2 (1.7%, 1.5% and 1.2%). Influenza virus B, enterovirus, respiratory syncytial virus, human coronavirus and parainfluenza virus 4 were rarely detected (<1%). Frequency of IFV A was highest among patients aged between 45–64 years (p < 0.001), while adenovirus among patients aged 14–17 years (p < 0.001), no differences was found in other RVs. The proportion of pandemic H1N1 increased with severity of pneumonia evaluated by PSI (P < 0.05). CONCLUSIONS: The proportion of RVs in CAP is higher than previously reported. IFV A pneumonia are usually found in patients older than 45 years, while, adenovirus pneumonia are common in adolescents and young adults. Pandemic H1N1 virus is still recognized by PSI as a high-severity pathogen. The findings contribute baseline data on viral CAP study in China.",2015 Feb 22,"['Qu, Jiu-Xin', 'Gu, Li', 'Pu, Zeng-Hui', 'Yu, Xiao-Min', 'Liu, Ying-Mei', 'Li, Ran', 'Wang, Yi-Min', 'Cao, Bin', 'Wang, Chen', None]",BMC Infect Dis,,,True
60bb4454a34fb7642d6805ff6261abc91809a135,PMC,"Drainage systems, an occluded source of sanitation related outbreaks",http://dx.doi.org/10.1186/s13690-014-0056-6,PMC4342212,25722855,CC BY,"BACKGROUND: Drainage systems and its role in sanitation related outbreaks are evident but still occluded once it has been installed. This current review evaluates if drainage systems can cause infections and thus be of clinical concern. METHOD: A review of the literature was analyzed. Papers, guidelines, and quality management systems have been considered. RESULTS: Adequate sanitation is fundamental and a prerequisite for safe life and productivity. In contrast, malfunctioning sanitation has been reported to cause outbreaks all over the world. In areas with no sanitation, diarrheal mortality is high and has been shown to decrease by 36% after interventions to improve sanitation. Often, infections are faeces associated and when present in wastewater and sewage sludge poses a high risk of infection upon exposure. Hence, there are working safety guidelines and in industries where infection reduction is essential strict quality assurance systems, i.e. HACCP (hazard analysis critical control points) and GMP (Good Manufacturing Practice) must be complied. Healthcare has recently taken interest in the HACCP system in their efforts to reduce healthcare associated infections as a response to increasing number of ineffective antibiotics and the threat of mortality rate like the pre-antibiotic era. The last few years have called for immediate action to contain the emergence of increasing resistant microorganisms. Resistance is obtained as a result of overuse and misuse of antibiotics in both healthcare and agriculture. Also, by the discharge of antibiotics from manufacturers, healthcare and society. One mechanism of development of novel resistant pathogens has been shown to be by effortless sharing of genetic mobile elements coding for resistance from microbes in the environment to human microbes. These pathogens have been sampled from the drainage systems. These were noticed owing to their possession of an unusual antibiotic resistance profile linking them to the outbreak. Often the cause of sanitation related outbreaks is due to inadequate sanitation and maintenance. However, in general these infections probably go unnoticed. CONCLUSION: Drainage systems and its maintenance, if neglected, could pose a threat in both community and healthcare causing infections as well as emergence of multi-resistant bacteria that could cause unpredictable clinical manifestations.",2015 Feb 26,"Blom, Kristina",Arch Public Health,,,True
473b926e3266337d27883cca29c6186faf3d7ba2,PMC,Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection,http://dx.doi.org/10.1371/journal.pone.0118345,PMC4342244,25719445,CC0,"Ebola virus (EBOV) causes a severe hemorrhagic disease with high fatality. Virus-like particles (VLPs) are a promising vaccine candidate against EBOV. We recently showed that VLPs protect mice from lethal EBOV infection when given before or after viral infection. To elucidate pathways through which VLPs confer post-exposure protection, we investigated the role of type I interferon (IFN) signaling. We found that VLPs lead to accelerated induction of IFN stimulated genes (ISGs) in liver and spleen of wild type mice, but not in Ifnar(-/-) mice. Accordingly, EBOV infected Ifnar(-/-) mice, unlike wild type mice succumbed to death even after VLP treatment. The ISGs induced in wild type mice included anti-viral proteins and negative feedback factors known to restrict viral replication and excessive inflammatory responses. Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. Together, this study indicates that VLPs afford post-exposure protection by promoting expeditious initiation of type I IFN signaling in the host.",2015 Feb 26,"['Ayithan, Natarajan', 'Bradfute, Steven B.', 'Anthony, Scott M.', 'Stuthman, Kelly S.', 'Bavari, Sina', 'Bray, Mike', 'Ozato, Keiko']",PLoS One,,,True
efc1b7d8cc09b229c5cd7cda3a8ff8446e0d8b63,PMC,"New Insights into Flavivirus Evolution, Taxonomy and Biogeographic History, Extended by Analysis of Canonical and Alternative Coding Sequences",http://dx.doi.org/10.1371/journal.pone.0117849,PMC4342338,25719412,CC BY,"To generate the most diverse phylogenetic dataset for the flaviviruses to date, we determined the genomic sequences and phylogenetic relationships of 14 flaviviruses, of which 10 are primarily associated with Culex spp. mosquitoes. We analyze these data, in conjunction with a comprehensive collection of flavivirus genomes, to characterize flavivirus evolutionary and biogeographic history in unprecedented detail and breadth. Based on the presumed introduction of yellow fever virus into the Americas via the transatlantic slave trade, we extrapolated a timescale for a relevant subset of flaviviruses whose evolutionary history, shows that different Culex-spp. associated flaviviruses have been introduced from the Old World to the New World on at least five separate occasions, with 2 different sets of factors likely to have contributed to the dispersal of the different viruses. We also discuss the significance of programmed ribosomal frameshifting in a central region of the polyprotein open reading frame in some mosquito-associated flaviviruses.",2015 Feb 26,"['Moureau, Gregory', 'Cook, Shelley', 'Lemey, Philippe', 'Nougairede, Antoine', 'Forrester, Naomi L.', 'Khasnatinov, Maxim', 'Charrel, Remi N.', 'Firth, Andrew E.', 'Gould, Ernest A.', 'de Lamballerie, Xavier']",PLoS One,,,True
f879891cd4353fbb6baa973c04bc1cf2dc3a3fd6,PMC,Field pathogenomics reveals the emergence of a diverse wheat yellow rust population,http://dx.doi.org/10.1186/s13059-015-0590-8,PMC4342793,25723868,CC BY,"BACKGROUND: Emerging and re-emerging pathogens imperil public health and global food security. Responding to these threats requires improved surveillance and diagnostic systems. Despite their potential, genomic tools have not been readily applied to emerging or re-emerging plant pathogens such as the wheat yellow (stripe) rust pathogen Puccinia striiformis f. sp. tritici (PST). This is due largely to the obligate parasitic nature of PST, as culturing PST isolates for DNA extraction remains slow and tedious. RESULTS: To counteract the limitations associated with culturing PST, we developed and applied a field pathogenomics approach by transcriptome sequencing infected wheat leaves collected from the field in 2013. This enabled us to rapidly gain insights into this emerging pathogen population. We found that the PST population across the United Kingdom (UK) underwent a major shift in recent years. Population genetic structure analyses revealed four distinct lineages that correlated to the phenotypic groups determined through traditional pathology-based virulence assays. Furthermore, the genetic diversity between members of a single population cluster for all 2013 PST field samples was much higher than that displayed by historical UK isolates, revealing a more diverse population of PST. CONCLUSIONS: Our field pathogenomics approach uncovered a dramatic shift in the PST population in the UK, likely due to a recent introduction of a diverse set of exotic PST lineages. The methodology described herein accelerates genetic analysis of pathogen populations and circumvents the difficulties associated with obligate plant pathogens. In principle, this strategy can be widely applied to a variety of plant pathogens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0590-8) contains supplementary material, which is available to authorized users.",2015 Feb 25,"['Hubbard, Amelia', 'Lewis, Clare M', 'Yoshida, Kentaro', 'Ramirez-Gonzalez, Ricardo H', 'de Vallavieille-Pope, Claude', 'Thomas, Jane', 'Kamoun, Sophien', 'Bayles, Rosemary', 'Uauy, Cristobal', 'Saunders, Diane GO']",Genome Biol,,,True
1dc4f757f425b080168840089f1f4d29bac75f51,PMC,Identifying Meteorological Drivers for the Seasonal Variations of Influenza Infections in a Subtropical City — Hong Kong,http://dx.doi.org/10.3390/ijerph120201560,PMC4344680,25635916,CC BY,"Compared with temperate areas, the understanding of seasonal variations of influenza infections is lacking in subtropical and tropical regions. Insufficient information about viral activity increases the difficulty of forecasting the disease burden and thus hampers official preparation efforts. Here we identified potential meteorological factors that drove the seasonal variations in influenza infections in a subtropical city, Hong Kong. We fitted the meteorological data and influenza mortality data from 2002 to 2009 in a Susceptible-Infected-Recovered model. From the results, air temperature was a common significant driver of seasonal patterns and cold temperature was associated with an increase in transmission intensity for most of the influenza epidemics. Except 2004, the fitted models with significant meteorological factors could account for more than 10% of the variance in additional to the null model. Rainfall was also found to be a significant driver of seasonal influenza, although results were less robust. The identified meteorological indicators could alert officials to take appropriate control measures for influenza epidemics, such as enhancing vaccination activities before cold seasons. Further studies are required to fully justify the associations.",2015 Feb 28,"['Chong, Ka Chun', 'Goggins, William', 'Zee, Benny Chung Ying', 'Wang, Maggie Haitian']",Int J Environ Res Public Health,,,True
d2b4b984732c78ae39fa9f699232153758583d51,PMC,Identifying Meteorological Drivers for the Seasonal Variations of Influenza Infections in a Subtropical City — Hong Kong,http://dx.doi.org/10.3390/ijerph120201560,PMC4344680,25635916,CC BY,"Compared with temperate areas, the understanding of seasonal variations of influenza infections is lacking in subtropical and tropical regions. Insufficient information about viral activity increases the difficulty of forecasting the disease burden and thus hampers official preparation efforts. Here we identified potential meteorological factors that drove the seasonal variations in influenza infections in a subtropical city, Hong Kong. We fitted the meteorological data and influenza mortality data from 2002 to 2009 in a Susceptible-Infected-Recovered model. From the results, air temperature was a common significant driver of seasonal patterns and cold temperature was associated with an increase in transmission intensity for most of the influenza epidemics. Except 2004, the fitted models with significant meteorological factors could account for more than 10% of the variance in additional to the null model. Rainfall was also found to be a significant driver of seasonal influenza, although results were less robust. The identified meteorological indicators could alert officials to take appropriate control measures for influenza epidemics, such as enhancing vaccination activities before cold seasons. Further studies are required to fully justify the associations.",2015 Feb 28,"['Chong, Ka Chun', 'Goggins, William', 'Zee, Benny Chung Ying', 'Wang, Maggie Haitian']",Int J Environ Res Public Health,,,False
9718efa7298b28b740938eeca415b1703ec6f689,PMC,Effects of ribavirin on the replication and genetic stability of porcine reproductive and respiratory syndrome virus,http://dx.doi.org/10.1186/s12917-015-0330-z,PMC4344762,25890207,CC BY,"BACKGROUND: Although modified live virus (MLV) vaccines are commonly used for porcine reproductive and respiratory syndrome virus (PRRSV) control, there have been safety concerns due to the quick reversion of MLV to virulence during replication in pigs. Previous studies have demonstrated that mutant viruses emerged from lethal mutagenesis driven by antiviral mutagens and that those viruses had higher genetic stability compared to their parental strains because they acquired resistance to random mutation. Thus, this strategy was explored to stabilize the PRRSV genome in the current study. RESULTS: Four antiviral mutagens (ribavirin, 5-fluorouracil, 5-azacytidine, and amiloride) were evaluated for their antiviral effects against VR2332, a prototype of type 2 PRRSV. Among the mutagens, ribavirin and 5-fluorouracil had significant antiviral effects against VR2332. Consequently, VR2332 was serially passaged in MARC-145 cells in the presence of ribavirin at several concentrations to facilitate the emergence of ribavirin-resistant mutants. Two ribavirin-resistant mutants, RVRp13 and RVRp22, emerged from serial passages in the presence of 0.1 and 0.2 mM ribavirin, respectively. The genetic stability of these resistant mutants was evaluated in MARC-145 cells and compared with VR2332. As expected, the ribavirin-resistant mutants exhibited higher genetic stability compared to their parental virus. CONCLUSIONS: In summary, ribavirin and 5-fluorouracil effectively suppressed PRRSV replication in MARC-145 cells. However, ribavirin-resistant mutants emerged when treated with low concentrations (≤0.2 mM) of ribavirin, and those mutants were genetically more stable during serial passages in cell culture.",2015 Feb 7,"['Khatun, Amina', 'Shabir, Nadeem', 'Yoon, Kyoung-Jin', 'Kim, Won-Il']",BMC Vet Res,,,True
621fb61c827a3f1f0c6c69849319ed45f6dc1f5b,PMC,Viral infections in outpatients with medically attended acute respiratory illness during the 2012–2013 influenza season,http://dx.doi.org/10.1186/s12879-015-0806-2,PMC4344779,25887948,CC BY,"BACKGROUND: While it is known that acute respiratory illness (ARI) is caused by an array of viruses, less is known about co-detections and the resultant comparative symptoms and illness burden. This study examined the co-detections, the distribution of viruses, symptoms, and illness burden associated with ARI between December 2012 and March 2013. METHODS: Outpatients with ARI were assayed for presence of 18 viruses using multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) to simultaneously detect multiple viruses. RESULTS: Among 935 patients, 60% tested positive for a single virus, 9% tested positive for ≥1 virus and 287 (31%) tested negative. Among children (<18 years), the respective distributions were 63%, 14%, and 23%; whereas for younger adults (18–49 years), the distributions were 58%, 8%, and 34% and for older adults (≥50 years) the distributions were 61%, 5%, and 32% (P < 0.001). Co-detections were more common in children than older adults (P = 0.01), and less frequent in households without children (P = 0.003). Most frequently co-detected viruses were coronavirus, respiratory syncytial virus, and influenza A virus. Compared with single viral infections, those with co-detections less frequently reported sore throat (P = 0.01), missed fewer days of school (1.1 vs. 2 days; P = 0.04), or work (2 vs. 3 days; P = 0.03); other measures of illness severity did not vary. CONCLUSIONS: Among outpatients with ARI, 69% of visits were associated with a viral etiology. Co-detections of specific clusters of viruses were observed in 9% of ARI cases particularly in children, were less frequent in households without children, and were less symptomatic (e.g., lower fever) than single infections.",2015 Feb 22,"['Zimmerman, Richard K', 'Rinaldo, Charles R', 'Nowalk, Mary Patricia', 'Balasubramani, GK', 'Moehling, Krissy K', 'Bullotta, Arlene', 'Eng, Heather F', 'Raviotta, Jonathan M', 'Sax, Theresa M', 'Wisniewski, Stephen']",BMC Infect Dis,,,True
78b305688d964809c3cd62063d7fa6ecf30ebbc9,PMC,A multiplex PCR assay for the detection of five influenza viruses using a dual priming oligonucleotide system,http://dx.doi.org/10.1186/s12879-015-0818-y,PMC4344991,25886516,CC BY,"BACKGROUND: A cost-effective, accurate and rapid simultaneous multiplex assay is required for testing and diagnoses of conventional and emerging viruses in clinical virology laboratories. We developed and optimized a dual priming oligonucleotide (DPO) multiplex PCR assay for detecting influenza viruses including seasonal H1N1, 2009 pandemic H1N1, H3N2, influenza B and H5N1. METHODS: The optimized multiplex DPO PCR was used to detect 233 clinical human samples. The results were compared to those obtained with RT-qPCR, conventional PCR and immunochromatographic assay. RESULTS: Specificity analysis revealed that the DPO PCR assay amplified each target virus without any cross-amplification. Statistical analysis demonstrated that the multiplex DPO-PCR sensitivity was higher than for the immunochromatographic assay and lower than for qPCR, while no significant difference was observed compared with conventional PCR, when detecting influenza A and B. Additional experiments using the same sample panel indicated no significant differences between the number of positive samples detected by multiplex DPO PCR and RT-qPCR when applying a Cq with a value lower than 30. CONCLUSIONS: The five-targeted simultaneous multiplex DPO PCR assay could be easily adopted into routine practice. This approach is cost effective with a short running time, low technical requirements for the detection of influenza virus and early diagnosis in clinical laboratories.",2015 Feb 25,"['Ma, Xuezheng', 'Xu, Huanzhou', 'Shi, Lei', 'Yang, Pengfei', 'Zhang, Liping', 'Sun, Xiaohong', 'Zhen, Wei', 'Hu, Kongxin']",BMC Infect Dis,,,True
ffdef5aa153fee8ed2cac3d1434c8ec54a67e1ae,PMC,A Bayesian Inferential Approach to Quantify the Transmission Intensity of Disease Outbreak,http://dx.doi.org/10.1155/2015/256319,PMC4345055,25784956,CC BY,"Background. Emergence of infectious diseases like influenza pandemic (H1N1) 2009 has become great concern, which posed new challenges to the health authorities worldwide. To control these diseases various studies have been developed in the field of mathematical modelling, which is useful tool for understanding the epidemiological dynamics and their dependence on social mixing patterns. Method. We have used Bayesian approach to quantify the disease outbreak through key epidemiological parameter basic reproduction number (R (0)), using effective contacts, defined as sum of the product of incidence cases and probability of generation time distribution. We have estimated R (0) from daily case incidence data for pandemic influenza A/H1N1 2009 in India, for the initial phase. Result. The estimated R (0) with 95% credible interval is consistent with several other studies on the same strain. Through sensitivity analysis our study indicates that infectiousness affects the estimate of R (0). Conclusion. Basic reproduction number R (0) provides the useful information to the public health system to do some effort in controlling the disease by using mitigation strategies like vaccination, quarantine, and so forth.",2015 Feb 15,"['Kadi, Adiveppa S.', 'Avaradi, Shivakumari R.']",Comput Math Methods Med,,,False
b50ee1febe5e4b252cbc70678de7272524377ca1,PMC,A Bayesian Inferential Approach to Quantify the Transmission Intensity of Disease Outbreak,http://dx.doi.org/10.1155/2015/256319,PMC4345055,25784956,CC BY,"Background. Emergence of infectious diseases like influenza pandemic (H1N1) 2009 has become great concern, which posed new challenges to the health authorities worldwide. To control these diseases various studies have been developed in the field of mathematical modelling, which is useful tool for understanding the epidemiological dynamics and their dependence on social mixing patterns. Method. We have used Bayesian approach to quantify the disease outbreak through key epidemiological parameter basic reproduction number (R (0)), using effective contacts, defined as sum of the product of incidence cases and probability of generation time distribution. We have estimated R (0) from daily case incidence data for pandemic influenza A/H1N1 2009 in India, for the initial phase. Result. The estimated R (0) with 95% credible interval is consistent with several other studies on the same strain. Through sensitivity analysis our study indicates that infectiousness affects the estimate of R (0). Conclusion. Basic reproduction number R (0) provides the useful information to the public health system to do some effort in controlling the disease by using mitigation strategies like vaccination, quarantine, and so forth.",2015 Feb 15,"['Kadi, Adiveppa S.', 'Avaradi, Shivakumari R.']",Comput Math Methods Med,,,True
758d365d79d74aee483623c5abeab0c682bf1ad3,PMC,CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production,http://dx.doi.org/10.1038/ncomms7217,PMC4346637,25692415,CC BY,"B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-κB-axis. The absence of this signalling cascade in naive Ceacam1(−/−) mice limits the survival of B cells. During systemic infection with cytopathic vesicular stomatitis virus, Ceacam1(−/−) mice can barely induce neutralizing antibody responses and die early after infection. We find, therefore, that CEACAM1 is a crucial regulator of B-cell survival, influencing B-cell numbers and protective antiviral antibody responses.",2015 Feb 18,"['Khairnar, Vishal', 'Duhan, Vikas', 'Maney, Sathish Kumar', 'Honke, Nadine', 'Shaabani, Namir', 'Pandyra, Aleksandra A.', 'Seifert, Marc', 'Pozdeev, Vitaly', 'Xu, Haifeng C.', 'Sharma, Piyush', 'Baldin, Fabian', 'Marquardsen, Florian', 'Merches, Katja', 'Lang, Elisabeth', 'Kirschning, Carsten', 'Westendorf, Astrid M.', 'Häussinger, Dieter', 'Lang, Florian', 'Dittmer, Ulf', 'Küppers, Ralf', 'Recher, Mike', 'Hardt, Cornelia', 'Scheffrahn, Inka', 'Beauchemin, Nicole', 'Göthert, Joachim R.', 'Singer, Bernhard B.', 'Lang, Philipp A.', 'Lang, Karl S.']",Nat Commun,,,True
b473fcfb0b124c50f252ea3087dd03e45cd81e29,PMC,CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production,http://dx.doi.org/10.1038/ncomms7217,PMC4346637,25692415,CC BY,"B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-κB-axis. The absence of this signalling cascade in naive Ceacam1(−/−) mice limits the survival of B cells. During systemic infection with cytopathic vesicular stomatitis virus, Ceacam1(−/−) mice can barely induce neutralizing antibody responses and die early after infection. We find, therefore, that CEACAM1 is a crucial regulator of B-cell survival, influencing B-cell numbers and protective antiviral antibody responses.",2015 Feb 18,"['Khairnar, Vishal', 'Duhan, Vikas', 'Maney, Sathish Kumar', 'Honke, Nadine', 'Shaabani, Namir', 'Pandyra, Aleksandra A.', 'Seifert, Marc', 'Pozdeev, Vitaly', 'Xu, Haifeng C.', 'Sharma, Piyush', 'Baldin, Fabian', 'Marquardsen, Florian', 'Merches, Katja', 'Lang, Elisabeth', 'Kirschning, Carsten', 'Westendorf, Astrid M.', 'Häussinger, Dieter', 'Lang, Florian', 'Dittmer, Ulf', 'Küppers, Ralf', 'Recher, Mike', 'Hardt, Cornelia', 'Scheffrahn, Inka', 'Beauchemin, Nicole', 'Göthert, Joachim R.', 'Singer, Bernhard B.', 'Lang, Philipp A.', 'Lang, Karl S.']",Nat Commun,,,False
8e15c84010f5ea9e602ae6e51f9ac12ee754a9c9,PMC,Ebola Policies That Hinder Epidemic Response by Limiting Scientific Discourse,http://dx.doi.org/10.4269/ajtmh.14-0803,PMC4347321,25561564,CC BY,"There is an unprecedented epidemic of Ebola virus disease (EVD) in west Africa. There has been a strong response from dedicated health professionals. However, there have also been irrational and fear-based responses that have contributed to misallocation of resources, stigma, and deincentivizing volunteers to combat Ebola at its source. Recently, the State of Louisiana Department of Health and Hospitals issued a ban on those coming from affected countries wishing to attend the annual meetings of American Society of Tropical Medicine and Hygiene and the American Public Health Association, both of which were held in New Orleans. We argue against such policies, question evidence and motivations, and discuss their practical and ethical implications in hampering effective responses to EVD by the scientific community. We aim to shed light on this issue and its implications for the future of public health interventions, reflect on the responsibility of health providers and professional societies as advocates for patients and the public health, and call for health professionals and societies to work to challenge inappropriate political responses to public health crises.",2015 Feb 4,"['Asgary, Ramin', 'Pavlin, Julie A.', 'Ripp, Jonathan A.', 'Reithinger, Richard', 'Polyak, Christina S.']",Am J Trop Med Hyg,,,True
11022b299f98034d0060f9c036333f1b9024d7a1,PMC,Evidence of infectivity of airborne porcine epidemic diarrhea virus and detection of airborne viral RNA at long distances from infected herds,http://dx.doi.org/10.1186/s13567-014-0073-z,PMC4347589,25017790,CC BY,"Porcine epidemic diarrhea virus (PEDV) spread rapidly after being diagnosed in the USA in April 2013. In this study we assessed whether PEDV could become airborne and if so, whether the virus was infectious. Air samples were collected both from a room containing experimentally infected pigs and at various distances from the outside of swine farms experiencing acute PEDV outbreaks. Results indicated presence of infectious PEDV in the air from experimentally infected pigs and genetic material of PEDV was detected up to 10 miles downwind from naturally infected farms. Airborne transmission should be considered as a potential route for PEDV dissemination.",2014 Jul 14,"['Alonso, Carmen', 'Goede, Dane P', 'Morrison, Robert B', 'Davies, Peter R', 'Rovira, Albert', 'Marthaler, Douglas G', 'Torremorell, Montserrat']",Vet Res,,,True
46b318ba828af275acaaf75fb723e88980f96043,PMC,Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis,http://dx.doi.org/10.1186/s13054-015-0764-5,PMC4348153,25888424,CC BY,"INTRODUCTION: Corticosteroids are used empirically in influenza A (H1N1) treatment despite lack of clear evidence for effective treatment. This study aims to assess the efficacy of corticosteroids treatment for H1N1 infection. METHODS: Systematic review and meta-analysis were used to estimate the efficacy of corticosteroids for the prevention of mortality in H1N1 infection. Databases searched included MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Clinical Trials and so on, and bibliographies of retrieved articles, from April 2009 to October 2014. We included both cohort studies and case-control studies reported in English or Chinese that compared treatment effects between corticosteroids and non-corticosteroids therapy in inpatients with H1N1 virus infection. Cohort studies employed mortality as outcome, and case-control studies employed deaths as cases and survivors as controls; both were assessed in this meta-analysis. RESULTS: In total twenty-three eligible studies were included. Both cohort studies (nine studies, n = 1,405) and case-control studies (14 studies, n = 4,700) showed a similar trend toward increased mortality (cohort studies relative risk was 1.85 with 95% confidence interval (CI) 1.46 to 2.33; case-control studies odds ratio was 4.22 with 95% CI 3.10 to 5.76). The results from both subgroup analyses and sensitive analyses were consistent with each other, showing that steroid treatment is associated with mortality. However, considering the fact that corticosteroids were tend to be used in sickest case-patients and heterogeneity was observed between studies, we cannot make a solid conclusion. CONCLUSIONS: Available evidence did not support the use of corticosteroids as standard care for patients with severe influenza. We conclude that further research is required. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0764-5) contains supplementary material, which is available to authorized users.",2015 Feb 20,"['Zhang, Yi', 'Sun, Wenjie', 'Svendsen, Erik R', 'Tang, Song', 'MacIntyre, Raina C', 'Yang, Peng', 'Zhang, Daitao', 'Wang, Quanyi']",Crit Care,,,False
29b0c94901ca75a77502042d007037709ecfe199,PMC,Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis,http://dx.doi.org/10.1186/s13054-015-0764-5,PMC4348153,25888424,CC BY,"INTRODUCTION: Corticosteroids are used empirically in influenza A (H1N1) treatment despite lack of clear evidence for effective treatment. This study aims to assess the efficacy of corticosteroids treatment for H1N1 infection. METHODS: Systematic review and meta-analysis were used to estimate the efficacy of corticosteroids for the prevention of mortality in H1N1 infection. Databases searched included MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Clinical Trials and so on, and bibliographies of retrieved articles, from April 2009 to October 2014. We included both cohort studies and case-control studies reported in English or Chinese that compared treatment effects between corticosteroids and non-corticosteroids therapy in inpatients with H1N1 virus infection. Cohort studies employed mortality as outcome, and case-control studies employed deaths as cases and survivors as controls; both were assessed in this meta-analysis. RESULTS: In total twenty-three eligible studies were included. Both cohort studies (nine studies, n = 1,405) and case-control studies (14 studies, n = 4,700) showed a similar trend toward increased mortality (cohort studies relative risk was 1.85 with 95% confidence interval (CI) 1.46 to 2.33; case-control studies odds ratio was 4.22 with 95% CI 3.10 to 5.76). The results from both subgroup analyses and sensitive analyses were consistent with each other, showing that steroid treatment is associated with mortality. However, considering the fact that corticosteroids were tend to be used in sickest case-patients and heterogeneity was observed between studies, we cannot make a solid conclusion. CONCLUSIONS: Available evidence did not support the use of corticosteroids as standard care for patients with severe influenza. We conclude that further research is required. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0764-5) contains supplementary material, which is available to authorized users.",2015 Feb 20,"['Zhang, Yi', 'Sun, Wenjie', 'Svendsen, Erik R', 'Tang, Song', 'MacIntyre, Raina C', 'Yang, Peng', 'Zhang, Daitao', 'Wang, Quanyi']",Crit Care,,,False
dd432e4c91aa16c92de344b4d93df7b4618d42e1,PMC,Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis,http://dx.doi.org/10.1186/s13054-015-0764-5,PMC4348153,25888424,CC BY,"INTRODUCTION: Corticosteroids are used empirically in influenza A (H1N1) treatment despite lack of clear evidence for effective treatment. This study aims to assess the efficacy of corticosteroids treatment for H1N1 infection. METHODS: Systematic review and meta-analysis were used to estimate the efficacy of corticosteroids for the prevention of mortality in H1N1 infection. Databases searched included MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Clinical Trials and so on, and bibliographies of retrieved articles, from April 2009 to October 2014. We included both cohort studies and case-control studies reported in English or Chinese that compared treatment effects between corticosteroids and non-corticosteroids therapy in inpatients with H1N1 virus infection. Cohort studies employed mortality as outcome, and case-control studies employed deaths as cases and survivors as controls; both were assessed in this meta-analysis. RESULTS: In total twenty-three eligible studies were included. Both cohort studies (nine studies, n = 1,405) and case-control studies (14 studies, n = 4,700) showed a similar trend toward increased mortality (cohort studies relative risk was 1.85 with 95% confidence interval (CI) 1.46 to 2.33; case-control studies odds ratio was 4.22 with 95% CI 3.10 to 5.76). The results from both subgroup analyses and sensitive analyses were consistent with each other, showing that steroid treatment is associated with mortality. However, considering the fact that corticosteroids were tend to be used in sickest case-patients and heterogeneity was observed between studies, we cannot make a solid conclusion. CONCLUSIONS: Available evidence did not support the use of corticosteroids as standard care for patients with severe influenza. We conclude that further research is required. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0764-5) contains supplementary material, which is available to authorized users.",2015 Feb 20,"['Zhang, Yi', 'Sun, Wenjie', 'Svendsen, Erik R', 'Tang, Song', 'MacIntyre, Raina C', 'Yang, Peng', 'Zhang, Daitao', 'Wang, Quanyi']",Crit Care,,,False
c6bf0f9e49e8bb42f0a2839b9316611a66626d7d,PMC,Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis,http://dx.doi.org/10.1186/s13054-015-0764-5,PMC4348153,25888424,CC BY,"INTRODUCTION: Corticosteroids are used empirically in influenza A (H1N1) treatment despite lack of clear evidence for effective treatment. This study aims to assess the efficacy of corticosteroids treatment for H1N1 infection. METHODS: Systematic review and meta-analysis were used to estimate the efficacy of corticosteroids for the prevention of mortality in H1N1 infection. Databases searched included MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Clinical Trials and so on, and bibliographies of retrieved articles, from April 2009 to October 2014. We included both cohort studies and case-control studies reported in English or Chinese that compared treatment effects between corticosteroids and non-corticosteroids therapy in inpatients with H1N1 virus infection. Cohort studies employed mortality as outcome, and case-control studies employed deaths as cases and survivors as controls; both were assessed in this meta-analysis. RESULTS: In total twenty-three eligible studies were included. Both cohort studies (nine studies, n = 1,405) and case-control studies (14 studies, n = 4,700) showed a similar trend toward increased mortality (cohort studies relative risk was 1.85 with 95% confidence interval (CI) 1.46 to 2.33; case-control studies odds ratio was 4.22 with 95% CI 3.10 to 5.76). The results from both subgroup analyses and sensitive analyses were consistent with each other, showing that steroid treatment is associated with mortality. However, considering the fact that corticosteroids were tend to be used in sickest case-patients and heterogeneity was observed between studies, we cannot make a solid conclusion. CONCLUSIONS: Available evidence did not support the use of corticosteroids as standard care for patients with severe influenza. We conclude that further research is required. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0764-5) contains supplementary material, which is available to authorized users.",2015 Feb 20,"['Zhang, Yi', 'Sun, Wenjie', 'Svendsen, Erik R', 'Tang, Song', 'MacIntyre, Raina C', 'Yang, Peng', 'Zhang, Daitao', 'Wang, Quanyi']",Crit Care,,,False
334bc72deded9b157e7f7fcc108fe0671cc41b50,PMC,Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis,http://dx.doi.org/10.1186/s13054-015-0764-5,PMC4348153,25888424,CC BY,"INTRODUCTION: Corticosteroids are used empirically in influenza A (H1N1) treatment despite lack of clear evidence for effective treatment. This study aims to assess the efficacy of corticosteroids treatment for H1N1 infection. METHODS: Systematic review and meta-analysis were used to estimate the efficacy of corticosteroids for the prevention of mortality in H1N1 infection. Databases searched included MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Clinical Trials and so on, and bibliographies of retrieved articles, from April 2009 to October 2014. We included both cohort studies and case-control studies reported in English or Chinese that compared treatment effects between corticosteroids and non-corticosteroids therapy in inpatients with H1N1 virus infection. Cohort studies employed mortality as outcome, and case-control studies employed deaths as cases and survivors as controls; both were assessed in this meta-analysis. RESULTS: In total twenty-three eligible studies were included. Both cohort studies (nine studies, n = 1,405) and case-control studies (14 studies, n = 4,700) showed a similar trend toward increased mortality (cohort studies relative risk was 1.85 with 95% confidence interval (CI) 1.46 to 2.33; case-control studies odds ratio was 4.22 with 95% CI 3.10 to 5.76). The results from both subgroup analyses and sensitive analyses were consistent with each other, showing that steroid treatment is associated with mortality. However, considering the fact that corticosteroids were tend to be used in sickest case-patients and heterogeneity was observed between studies, we cannot make a solid conclusion. CONCLUSIONS: Available evidence did not support the use of corticosteroids as standard care for patients with severe influenza. We conclude that further research is required. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0764-5) contains supplementary material, which is available to authorized users.",2015 Feb 20,"['Zhang, Yi', 'Sun, Wenjie', 'Svendsen, Erik R', 'Tang, Song', 'MacIntyre, Raina C', 'Yang, Peng', 'Zhang, Daitao', 'Wang, Quanyi']",Crit Care,,,True
34483f6b88d4999066d631b65cdf0f256d305b6f,PMC,Evaluation and mechanism for outcomes exploration of providing public health care in contract service in Rural China: a multiple-case study with complex adaptive systems design,http://dx.doi.org/10.1186/s12889-015-1540-9,PMC4349463,25880965,CC BY,"BACKGROUND: The Chinese government has increased the funding for public health in 2009 and experimentally applied a contract service policy (could be seen as a counterpart to family medicine) in 15 counties to promote public health services in the rural areas in 2013. The contract service aimed to convert village doctors, who had privately practiced for decades, into general practitioners under the government management, and better control the rampant chronic diseases. This study made a rare attempt to assess the effectiveness of public health services delivered under the contract service policy, explore the influencing mechanism and draw the implications for the policy extension in the future. METHODS: Three pilot counties and a non-pilot one with heterogeneity in economic and health development from east to west of China were selected by a purposive sampling method. The case study methods by document collection, non-participant observation and interviews (including key informant interview and focus group interview) with 84 health providers and 20 demanders in multiple level were applied in this study. A thematic approach was used to compare diverse outcomes and analyze mechanism in the complex adaptive systems framework. RESULTS: Without sufficient incentives, the public health services were not conducted effectively, regardless of the implementation of the contract policy. To appropriately increase the funding for public health by local finance and properly allocate subsidy to village doctors was one of the most effective approaches to stimulate health providers and demanders’ positivity and promote the policy implementation. County health bureaus acted as the most crucial agents among the complex public health systems. Their mental models influenced by the compound and various environments around them led to the diverse outcomes. If they could provide extra incentives and make the contexts of the systems ripe enough for change, the health providers and demanders would be receptive to the transition of the policy. CONCLUSIONS: The innovative fund raising measures could be taken by relatively developed counties of China to conduct public health services. Policymakers could take systems thinking as a useful tool to design plans and predict the unintended outcomes during the process of public health reforms.",2015 Feb 27,"['Zhou, Huixuan', 'Zhang, Shengfa', 'Zhang, Weijun', 'Wang, Fugang', 'Zhong, You', 'Gu, Linni', 'Qu, Zhiyong', 'Tian, Donghua']",BMC Public Health,,,True
7bb2233fecf687276332f5cfe4630d5286966390,PMC,"Improving the large scale purification of the HIV microbicide, griffithsin",http://dx.doi.org/10.1186/s12896-015-0120-5,PMC4349730,25887919,CC BY,"BACKGROUND: Griffithsin is a broad spectrum antiviral lectin that inhibits viral entry and maturation processes through binding clusters of oligomannose glycans on viral envelope glycoproteins. An efficient, scaleable manufacturing process for griffithsin active pharmaceutical ingredient (API) is essential for particularly cost-sensitive products such as griffithsin -based topical microbicides for HIV-1 prevention in resource poor settings. Our previously published purification method used ceramic filtration followed by two chromatography steps, resulting in a protein recovery of 30%. Our objective was to develop a scalable purification method for griffithsin expressed in Nicotiana benthamiana plants that would increase yield, reduce production costs, and simplify manufacturing techniques. Considering the future need to transfer griffithsin manufacturing technology to resource poor areas, we chose to focus modifying the purification process, paying particular attention to introducing simple, low-cost, and scalable procedures such as use of temperature, pH, ion concentration, and filtration to enhance product recovery. RESULTS: We achieved >99% pure griffithsin API by generating the initial green juice extract in pH 4 buffer, heating the extract to 55°C, incubating overnight with a bentonite MgCl(2) mixture, and final purification with Capto™ multimodal chromatography. Griffithsin extracted with this protocol maintains activity comparable to griffithsin purified by the previously published method and we are able to recover a substantially higher yield: 88 ± 5% of griffithsin from the initial extract. The method was scaled to produce gram quantities of griffithsin with high yields, low endotoxin levels, and low purification costs maintained. CONCLUSIONS: The methodology developed to purify griffithsin introduces and develops multiple tools for purification of recombinant proteins from plants at an industrial scale. These tools allow for robust cost-effective production and purification of griffithsin. The methodology can be readily scaled to the bench top or industry and process components can be used for purification of additional proteins based on biophysical characteristics.",2015 Feb 22,"['Fuqua, Joshua L', 'Wanga, Valentine', 'Palmer, Kenneth E']",BMC Biotechnol,,,True
f02529d9be6c7576b60d295c4e04d15a9a432614,PMC,The C-Terminal Sequence of IFITM1 Regulates Its Anti-HIV-1 Activity,http://dx.doi.org/10.1371/journal.pone.0118794,PMC4349745,25738301,CC BY,"The interferon-inducible transmembrane (IFITM) proteins inhibit a wide range of viruses. We previously reported the inhibition of human immunodeficiency virus type 1 (HIV-1) strain BH10 by human IFITM1, 2 and 3. It is unknown whether other HIV-1 strains are similarly inhibited by IFITMs and whether there exists viral countermeasure to overcome IFITM inhibition. We report here that the HIV-1 NL4-3 strain (HIV-1(NL4-3)) is not restricted by IFITM1 and its viral envelope glycoprotein is partly responsible for this insensitivity. However, HIV-1(NL4-3) is profoundly inhibited by an IFITM1 mutant, known as Δ(117–125), which is deleted of 9 amino acids at the C-terminus. In contrast to the wild type IFITM1, which does not affect HIV-1 entry, the Δ(117–125) mutant diminishes HIV-1(NL4-3) entry by 3-fold. This inhibition correlates with the predominant localization of Δ(117–125) to the plasma membrane where HIV-1 entry occurs. In spite of strong conservation of IFITM1 among most species, mouse IFITM1 is 19 amino acids shorter at its C-terminus as compared to human IFITM1 and, like the human IFITM1 mutant Δ(117–125), mouse IFITM1 also inhibits HIV-1 entry. This is the first report illustrating the role of viral envelope protein in overcoming IFITM1 restriction. The results also demonstrate the importance of the C-terminal region of IFITM1 in modulating the antiviral function through controlling protein subcellular localization.",2015 Mar 4,"['Jia, Rui', 'Ding, Shilei', 'Pan, Qinghua', 'Liu, Shan-Lu', 'Qiao, Wentao', 'Liang, Chen']",PLoS One,,,True
62dd39338a12f7b81ae4e79e030c238c9ddaedfe,PMC,A Novel Video Tracking Method to Evaluate the Effect of Influenza Infection and Antiviral Treatment on Ferret Activity,http://dx.doi.org/10.1371/journal.pone.0118780,PMC4349809,25738900,CC BY,"Ferrets are the preferred animal model to assess influenza virus infection, virulence and transmission as they display similar clinical symptoms and pathogenesis to those of humans. Measures of disease severity in the ferret include weight loss, temperature rise, sneezing, viral shedding and reduced activity. To date, the only available method for activity measurement has been the assignment of an arbitrary score by a ‘blind’ observer based on pre-defined responsiveness scale. This manual scoring method is subjective and can be prone to bias. In this study, we described a novel video-tracking methodology for determining activity changes in a ferret model of influenza infection. This method eliminates the various limitations of manual scoring, which include the need for a sole ‘blind’ observer and the requirement to recognise the ‘normal’ activity of ferrets in order to assign relative activity scores. In ferrets infected with an A(H1N1)pdm09 virus, video-tracking was more sensitive than manual scoring in detecting ferret activity changes. Using this video-tracking method, oseltamivir treatment was found to ameliorate the effect of influenza infection on activity in ferret. Oseltamivir treatment of animals was associated with an improvement in clinical symptoms, including reduced inflammatory responses in the upper respiratory tract, lower body weight loss and a smaller rise in body temperature, despite there being no significant reduction in viral shedding. In summary, this novel video-tracking is an easy-to-use, objective and sensitive methodology for measuring ferret activity.",2015 Mar 4,"['Oh, Ding Yuan', 'Barr, Ian G.', 'Hurt, Aeron C.']",PLoS One,,,True
6777d788e99e108bf3439ed5a79ac921ee60d06e,PMC,Endemic zoonoses in the tropics: a public health problem hiding in plain sight,http://dx.doi.org/10.1136/vr.h798,PMC4350138,25722334,CC BY,"Zoonotic diseases are a significant burden on animal and human health, particularly in developing countries. Despite recognition of this fact, endemic zoonoses often remain undiagnosed in people, instead being mistaken for febrile diseases such as malaria. Here, as part of Veterinary Record's ongoing series of articles on One Health, a multidisciplinary team of researchers from Scotland, Tanzania and New Zealand argues that a One Health approach is needed to effectively combat these diseases",2015 Feb 28,"['Halliday, Jo E. B.', 'Allan, Kathryn J.', 'Ekwem, Divine', 'Cleaveland, Sarah', 'Kazwala, Rudovick R.', 'Crump, John A.']",Vet Rec,,,True
0093f9ae0861afc0d29fff935ae6a3af898cea00,PMC,Emergence of infectious malignant thrombocytopenia in Japanese macaques (Macaca fuscata) by SRV-4 after transmission to a novel host,http://dx.doi.org/10.1038/srep08850,PMC4351523,25743183,CC BY,"We discovered a lethal hemorrhagic syndrome arising from severe thrombocytopenia in Japanese macaques kept at the Primate Research Institute, Kyoto University. Extensive investigation identified that simian retrovirus type 4 (SRV-4) was the causative agent of the disease. SRV-4 had previously been isolated only from cynomolgus macaques in which it is usually asymptomatic. We consider that the SRV-4 crossed the so-called species barrier between cynomolgus and Japanese macaques, leading to extremely severe acute symptoms in the latter. Infectious agents that cross the species barrier occasionally amplify in virulence, which is not observed in the original hosts. In such cases, the new hosts are usually distantly related to the original hosts. However, Japanese macaques are closely related to cynomolgus macaques, and can even hybridize when given the opportunity. This lethal outbreak of a novel pathogen in Japanese macaques highlights the need to modify our expectations about virulence with regards crossing species barriers.",2015 Mar 6,"['Okamoto, Munehiro', 'Miyazawa, Takayuki', 'Morikawa, Shigeru', 'Ono, Fumiko', 'Nakamura, Shota', 'Sato, Eiji', 'Yoshida, Tomoyuki', 'Yoshikawa, Rokusuke', 'Sakai, Kouji', 'Mizutani, Tetsuya', 'Nagata, Noriyo', 'Takano, Jun-ichiro', 'Okabayashi, Sachi', 'Hamano, Masataka', 'Fujimoto, Koji', 'Nakaya, Takaaki', 'Iida, Tetsuya', 'Horii, Toshihiro', 'Miyabe-Nishiwaki, Takako', 'Watanabe, Akino', 'Kaneko, Akihisa', 'Saito, Akatsuki', 'Matsui, Atsushi', 'Hayakawa, Toshiyuki', 'Suzuki, Juri', 'Akari, Hirofumi', 'Matsuzawa, Tetsuro', 'Hirai, Hirohisa']",Sci Rep,,,True
d2c64d81f9871f7b84cc90c81069098630e30dc4,PMC,Emergence of infectious malignant thrombocytopenia in Japanese macaques (Macaca fuscata) by SRV-4 after transmission to a novel host,http://dx.doi.org/10.1038/srep08850,PMC4351523,25743183,CC BY,"We discovered a lethal hemorrhagic syndrome arising from severe thrombocytopenia in Japanese macaques kept at the Primate Research Institute, Kyoto University. Extensive investigation identified that simian retrovirus type 4 (SRV-4) was the causative agent of the disease. SRV-4 had previously been isolated only from cynomolgus macaques in which it is usually asymptomatic. We consider that the SRV-4 crossed the so-called species barrier between cynomolgus and Japanese macaques, leading to extremely severe acute symptoms in the latter. Infectious agents that cross the species barrier occasionally amplify in virulence, which is not observed in the original hosts. In such cases, the new hosts are usually distantly related to the original hosts. However, Japanese macaques are closely related to cynomolgus macaques, and can even hybridize when given the opportunity. This lethal outbreak of a novel pathogen in Japanese macaques highlights the need to modify our expectations about virulence with regards crossing species barriers.",2015 Mar 6,"['Okamoto, Munehiro', 'Miyazawa, Takayuki', 'Morikawa, Shigeru', 'Ono, Fumiko', 'Nakamura, Shota', 'Sato, Eiji', 'Yoshida, Tomoyuki', 'Yoshikawa, Rokusuke', 'Sakai, Kouji', 'Mizutani, Tetsuya', 'Nagata, Noriyo', 'Takano, Jun-ichiro', 'Okabayashi, Sachi', 'Hamano, Masataka', 'Fujimoto, Koji', 'Nakaya, Takaaki', 'Iida, Tetsuya', 'Horii, Toshihiro', 'Miyabe-Nishiwaki, Takako', 'Watanabe, Akino', 'Kaneko, Akihisa', 'Saito, Akatsuki', 'Matsui, Atsushi', 'Hayakawa, Toshiyuki', 'Suzuki, Juri', 'Akari, Hirofumi', 'Matsuzawa, Tetsuro', 'Hirai, Hirohisa']",Sci Rep,,,False
035dfb6e2398c95bbf6b65db97b443908a43e093,PMC,RIEMS: a software pipeline for sensitive and comprehensive taxonomic classification of reads from metagenomics datasets,http://dx.doi.org/10.1186/s12859-015-0503-6,PMC4351923,25886935,CC BY,"BACKGROUND: Fuelled by the advent and subsequent development of next generation sequencing technologies, metagenomics became a powerful tool for the analysis of microbial communities both scientifically and diagnostically. The biggest challenge is the extraction of relevant information from the huge sequence datasets generated for metagenomics studies. Although a plethora of tools are available, data analysis is still a bottleneck. RESULTS: To overcome the bottleneck of data analysis, we developed an automated computational workflow called RIEMS – Reliable Information Extraction from Metagenomic Sequence datasets. RIEMS assigns every individual read sequence within a dataset taxonomically by cascading different sequence analyses with decreasing stringency of the assignments using various software applications. After completion of the analyses, the results are summarised in a clearly structured result protocol organised taxonomically. The high accuracy and performance of RIEMS analyses were proven in comparison with other tools for metagenomics data analysis using simulated sequencing read datasets. CONCLUSIONS: RIEMS has the potential to fill the gap that still exists with regard to data analysis for metagenomics studies. The usefulness and power of RIEMS for the analysis of genuine sequencing datasets was demonstrated with an early version of RIEMS in 2011 when it was used to detect the orthobunyavirus sequences leading to the discovery of Schmallenberg virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0503-6) contains supplementary material, which is available to authorized users.",2015 Mar 3,"['Scheuch, Matthias', 'Höper, Dirk', 'Beer, Martin']",BMC Bioinformatics,,,True
a8f7ee410837cdbf7f974543e432d161fb70cd11,PMC,"The Role of Misshapen NCK-related kinase (MINK), a Novel Ste20 Family Kinase, in the IRES-Mediated Protein Translation of Human Enterovirus 71",http://dx.doi.org/10.1371/journal.ppat.1004686,PMC4352056,25747578,CC BY,"Human Enterovirus 71 (EV71) commonly causes Hand, Foot and Mouth Disease in young children, and occasional occurrences of neurological complications can be fatal. In this study, a high-throughput cell-based screening on the serine/threonine kinase siRNA library was performed to identify potential antiviral agents against EV71 replication. Among the hits, Misshapen/NIKs-related kinase (MINK) was selected for detailed analysis due to its strong inhibitory profile and novelty. In the investigation of the stage at which MINK is involved in EV71 replication, virus RNA transfection in MINK siRNA-treated cells continued to cause virus inhibition despite bypassing the normal entry pathway, suggesting its involvement at the post-entry stage. We have also shown that viral RNA and protein expression level was significantly reduced upon MINK silencing, suggesting its involvement in viral protein synthesis which feeds into viral RNA replication process. Through proteomic analysis and infection inhibition assay, we found that the activation of MINK was triggered by early replication events, instead of the binding and entry of the virus. Proteomic analysis on the activation profile of p38 Mitogen-activated Protein Kinase (MAPK) indicated that the phosphorylation of p38 MAPK was stimulated by EV71 infection upon MINK activation. Luciferase reporter assay further revealed that the translation efficiency of the EV71 internal ribosomal entry site (IRES) was reduced after blocking the MINK/p38 MAPK pathway. Further investigation on the effect of MINK silencing on heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) localisation demonstrated that cytoplasmic relocalisation of hnRNP A1 upon EV71 infection may be facilitated via the MINK/p38 MAPK pathway which then positively regulates the translation of viral RNA transcripts. These novel findings hence suggest that MINK plays a functional role in the IRES-mediated translation of EV71 viral RNA and may provide a potential target for the development of specific antiviral strategies against EV71 infection.",2015 Mar 6,"['Leong, Shi Yun', 'Ong, Bryan Kit Teck', 'Chu, Justin Jang Hann']",PLoS Pathog,,,True
3ecefecb6bd94b90680980f6d67045f7536d3410,PMC,Constant up-regulation of BiP/GRP78 expression prevents virus-induced apoptosis in BHK-21 cells with Japanese encephalitis virus persistent infection,http://dx.doi.org/10.1186/s12985-015-0269-5,PMC4352245,25888736,CC BY,"BACKGROUND: Persistent infection of the Japanese Encephalitis Virus (JEV) has been reported in clinical cases, experimental animals, and various cell culture systems. We previously reported the establishment of spontaneous JEV persistent infection, assisted by defective interfering particle accumulation and/or attenuated helper viruses, in BHK-21 cells devoid of virus-induced apoptosis, cBS6-2 and cBS6-3. However, cell-specific factors may play important roles in controlling JEV replication and have never been assessed for this specific phenomenon. Recent evidence suggests that viruses have evolved various mechanisms to cope with endoplasmic reticulum stress signaling pathways for their efficient amplification and transmission, including the unfolded protein response (UPR). RESULTS: To identify the host cell factors that affect JEV persistence, we investigated the expression of essential UPR factors in cBS6-2 and cBS6-3 cells. Of the selected UPR factors tested, the most noticeable deviations from those of the normal BHK-21 cells with JEV acute infection were as follows: the suppression of C/EBP homologous binding protein (CHOP) and the constant up-regulation of immunoglobulin binding protein (BiP) expression in cBS6-2 and cBS6-3 cells. In JEV acute infection on normal BHK-21 cells, silencing CHOP expression through specific siRNA blocked cell death almost completely. Meanwhile, depletion of BiP by specific siRNA unlocked CHOP expression in cBS6-2 and cBS6-3 cells, resulting in massive cell death. Fulminant apoptotic cell death for both cell clones on tunicamycin treatment revealed that the JEV persistently infected cells still contained functional arms for cell fate decisions. CONCLUSIONS: BHK-21 cells with JEV persistent infection strive against virus-induced apoptosis through constant up-regulation of BiP expression, resulting in the complete depletion of CHOP even with apparent virus amplification in the cells. Accordingly, the attenuation of virus replication as well as the modifications to cell metabolism could be additional factors contributing to the development of JEV persistent infection in mammalian cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0269-5) contains supplementary material, which is available to authorized users.",2015 Feb 26,"['Lyoo, Hey Rhyoung', 'Park, Soo Young', 'Kim, Ji Young', 'Jeong, Yong Seok']",Virol J,,,False
3b9aeb17bc120925271e7443ebaa19f69ed34a25,PMC,Constant up-regulation of BiP/GRP78 expression prevents virus-induced apoptosis in BHK-21 cells with Japanese encephalitis virus persistent infection,http://dx.doi.org/10.1186/s12985-015-0269-5,PMC4352245,25888736,CC BY,"BACKGROUND: Persistent infection of the Japanese Encephalitis Virus (JEV) has been reported in clinical cases, experimental animals, and various cell culture systems. We previously reported the establishment of spontaneous JEV persistent infection, assisted by defective interfering particle accumulation and/or attenuated helper viruses, in BHK-21 cells devoid of virus-induced apoptosis, cBS6-2 and cBS6-3. However, cell-specific factors may play important roles in controlling JEV replication and have never been assessed for this specific phenomenon. Recent evidence suggests that viruses have evolved various mechanisms to cope with endoplasmic reticulum stress signaling pathways for their efficient amplification and transmission, including the unfolded protein response (UPR). RESULTS: To identify the host cell factors that affect JEV persistence, we investigated the expression of essential UPR factors in cBS6-2 and cBS6-3 cells. Of the selected UPR factors tested, the most noticeable deviations from those of the normal BHK-21 cells with JEV acute infection were as follows: the suppression of C/EBP homologous binding protein (CHOP) and the constant up-regulation of immunoglobulin binding protein (BiP) expression in cBS6-2 and cBS6-3 cells. In JEV acute infection on normal BHK-21 cells, silencing CHOP expression through specific siRNA blocked cell death almost completely. Meanwhile, depletion of BiP by specific siRNA unlocked CHOP expression in cBS6-2 and cBS6-3 cells, resulting in massive cell death. Fulminant apoptotic cell death for both cell clones on tunicamycin treatment revealed that the JEV persistently infected cells still contained functional arms for cell fate decisions. CONCLUSIONS: BHK-21 cells with JEV persistent infection strive against virus-induced apoptosis through constant up-regulation of BiP expression, resulting in the complete depletion of CHOP even with apparent virus amplification in the cells. Accordingly, the attenuation of virus replication as well as the modifications to cell metabolism could be additional factors contributing to the development of JEV persistent infection in mammalian cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0269-5) contains supplementary material, which is available to authorized users.",2015 Feb 26,"['Lyoo, Hey Rhyoung', 'Park, Soo Young', 'Kim, Ji Young', 'Jeong, Yong Seok']",Virol J,,,True
c32c7f59bd902e4b2ef9fbe78e87c1d683de2d42,PMC,Novel adenovirus detected in captive bottlenose dolphins (Tursiops truncatus) suffering from self-limiting gastroenteritis,http://dx.doi.org/10.1186/s12917-015-0367-z,PMC4352565,25888777,CC BY,"BACKGROUND: Adenoviruses are common pathogens in vertebrates, including humans. In marine mammals, adenovirus has been associated with fatal hepatitis in sea lions. However, only in rare cases have adenoviruses been detected in cetaceans, where no clear correlation was found between presence of the virus and disease status. CASE PRESENTATION: A novel adenovirus was identified in four captive bottlenose dolphins with self-limiting gastroenteritis. Viral detection and identification were achieved by: PCR-amplification from fecal samples; sequencing of partial adenovirus polymerase (pol) and hexon genes; producing the virus in HeLa cells, with PCR and immunofluorescence detection, and with sequencing of the amplified pol and hexon gene fragments. A causative role of this adenovirus for gastroenteritis was suggested by: 1) we failed to identify other potential etiological agents; 2) the exclusive detection of this novel adenovirus and of seropositivity for canine adenoviruses 1 and 2 in the four sick dolphins, but not in 10 healthy individuals of the same captive population; and 3) the virus disappeared from feces after clinical signs receded. The partial sequences of the amplified fragments of the pol and hexon genes were closest to those of adenoviruses identified in sea lions with fatal adenoviral hepatitis, and to a Genbank-deposited sequence obtained from a harbour porpoise. CONCLUSION: These data suggest that adenovirus can cause self-limiting gastroenteritis in dolphins. This adenoviral infection can be detected by serology and by PCR detection in fecal material. Lack of signs of hepatitis in sick dolphins may reflect restricted tissue tropism or virulence of this adenovirus compared to those of the adenovirus identified in sea lions. Gene sequence-based phylogenetic analysis supports a common origin of adenoviruses that affect sea mammals. Our findings suggest the need for vigilance against adenoviruses in captive and wild dolphin populations.",2015 Mar 7,"['Rubio-Guerri, Consuelo', 'García-Párraga, Daniel', 'Nieto-Pelegrín, Elvira', 'Melero, Mar', 'Álvaro, Teresa', 'Valls, Mónica', 'Crespo, Jose Luis', 'Sánchez-Vizcaíno, Jose Manuel']",BMC Vet Res,,,True
589045646462acd78b115142b5464cca998f26d7,PMC,Src inhibitor reduces permeability without disturbing vascularization and prevents bone destruction in steroid-associated osteonecrotic lesions in rabbits,http://dx.doi.org/10.1038/srep08856,PMC4352921,25748225,CC BY,"To examine the therapeutic effect of Src inhibitor on the VEGF mediating vascular hyperpermeability and bone destruction within steroid-associated osteonecrotic lesions in rabbits. Rabbits with high risk for progress to destructive repair in steroid-associated osteonecrosis were selected according to our published protocol. The selected rabbits were systemically administrated with either Anti-VEGF antibody (Anti-VEGF Group) or Src inhibitor (Src-Inhibition Group) or VEGF (VEGF-Supplement Group) or a combination of VEGF and Src inhibitor (Supplement & Inhibition Group) or control vehicle (Control Group) for 4 weeks. At 0, 2 and 4 weeks after administration, in vivo dynamic MRI, micro-CT based-angiography, histomorphometry and immunoblotting were employed to evaluate the vascular and skeletal events in different groups. The incidence of the destructive repair in the Anti-VEGF Group, Src-Inhibition Group and Supplement & Inhibition Group was all significantly lower than that in the Control Group. The angiogenesis was promoted in VEGF-Supplement Group, Src-Inhibition Group and Supplement & Inhibition Group, while the hyperpermeability was inhibited in Anti-VEGF Group, Src-Inhibition Group and Supplement & Inhibition Group. The trabecular structure was improved in Src-Inhibition Group and Supplement & Inhibition Group. Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis.",2015 Mar 9,"['He, Yi-Xin', 'Liu, Jin', 'Guo, Baosheng', 'Wang, Yi-Xiang', 'Pan, Xiaohua', 'Li, Defang', 'Tang, Tao', 'Chen, Yang', 'Peng, Songlin', 'Bian, Zhaoxiang', 'Liang, Zicai', 'Zhang, Bao-Ting', 'Lu, Aiping', 'Zhang, Ge']",Sci Rep,,,True
9146df7c1faca31203b1e903f59662067faebb69,PMC,Sparse evidence of MERS-CoV infection among animal workers living in Southern Saudi Arabia during 2012,http://dx.doi.org/10.1111/irv.12287,PMC4353318,25470665,CC BY,Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging viral pathogen that primarily causes respiratory illness. We conducted a seroprevalence study of banked human serum samples collected in 2012 from Southern Saudi Arabia. Sera from 300 animal workers (17% with daily camel exposure) and 50 non-animal-exposed controls were examined for serological evidence of MERS-CoV infection by a pseudoparticle MERS-CoV spike protein neutralization assay. None of the sera reproducibly neutralized the MERS-CoV-pseudotyped lentiviral vector. These data suggest that serological evidence of zoonotic transmission of MERS-CoV was not common among animal workers in Southern Saudi Arabia during July 2012.,2015 Mar 3,"['Memish, Ziad A', 'Alsahly, Ahmad', 'Masri, Malak al', 'Heil, Gary L', 'Anderson, Benjamin D', 'Peiris, Malik', 'Khan, Salah Uddin', 'Gray, Gregory C']",Influenza Other Respir Viruses,,,True
ca13097c0bc4ca9abed010fa69c56531749da4dd,PMC,Zanamivir versus trivalent split virus influenza vaccine: a pilot randomized trial,http://dx.doi.org/10.1111/irv.12301,PMC4353320,25557838,CC BY,"BACKGROUND: Healthcare workers may be exposed to people with respiratory viral infections more often than other working adults. Understanding the risk and the effectiveness of different preventive measures is of great importance. OBJECTIVES: To estimate adherence to prophylactic antiviral medication for a full influenza season, to the compare efficacy of antiviral prophylaxis to that of the seasonal influenza vaccine and to identify exposures that increase risk of acute respiratory illnesses (ARI) in healthy adults. METHODS: Participants were randomized 1:2 to receive the 2008–2009 influenza vaccine or daily prophylaxis with 10 mg of zanamivir during the season. Web-based questionnaires collected information on demographics, symptoms, exposures, medication use and side effects. RESULTS: Sixty-four healthy adults were recruited in November 2008. Three of 40 active participants discontinued zanamivir due to side effects; the remaining 37 took >85% of scheduled doses for a median of 121 days. Symptomatic, laboratory-confirmed influenza was detected in one person randomized to zanamivir (2·5%) and 2/20 (10%) who received the vaccine (P = 0·25). Forty-seven participants reported 109 episodes of ARI. Factors associated with an ARI were exposure to a spouse (OR 7·2), child (OR 2·4) or patient (OR 2·0) with symptoms of an ARI in the previous 7 days. CONCLUSIONS: Breakthrough influenza infection occurred in both vaccinated participants and those receiving antiviral prophylaxis. Most adults were willing and able to comply with season-long prophylaxis. Report of recent exposure to family members and patients with an ARI increased the risk of developing an ARI in healthy adults.",2015 Mar 4,"['Coleman, Brenda L', 'Fadel, Shaza A', 'Drews, Steven J', 'Hatchette, Todd F', 'McGeer, Allison J']",Influenza Other Respir Viruses,,,True
5d6c145129db8973b797726818f229dfaa997f11,PMC,Prevalence and Correlation of Infectious Agents in Hospitalized Children with Acute Respiratory Tract Infections in Central China,http://dx.doi.org/10.1371/journal.pone.0119170,PMC4353725,25751402,CC BY,"Acute respiratory tract infections (ARTIs) are associated with significant morbidity and mortality worldwide, especially in children under the age of 5 years. Almost 2 million children die from ARTIs each year, and most of them are from developing countries. The prevalence and correlation of pathogens in ARTIs are poorly understood, but are critical for improving case prevention, treatment, and management. In this study, we investigated the prevalence and correlation of infectious agents in children with ARTIs. A total of 39,756 children with one or more symptoms, including fever, cough, sore throat, tonsillitis, pharyngitis, herpangina, pneumonia, and bronchiolitis, were enrolled in the study. All patients were hospitalized in Wuhan Children’s Hospital between October 1, 2010 and September 30, 2012, and were evaluated for infectious agents. Pathogens, including Mycoplasma pneumoniae, influenza A virus, influenza B virus, adenoviruses, respiratory syncytial virus, parainfluenza virus, Legionella pneumophila, Chlamydophila pneumoniae, and Coxiella burnetii, were screened simultaneously in patient blood samples using anti-pathogen IgM tests. Regression analysis was used to reveal correlations among the pathogens. Our results showed that one or more pathogens were identified in 10,206 patients, and that Mycoplasma pneumoniae, adenoviruses, and influenza B virus were the leading infectious agents. Mixed-infections of pathogens were detected in 2,391 cases, with Mycoplasma pneumoniae as the most frequent pathogen. The most common agents in the co-infections were Mycoplasma pneumoniae and influenza B virus. Regression analysis revealed a linear correlation between the proportion of mixed infections and the incidence of multi-pathogen infections. The prevalence of infectious agents in children with ARTIs was determined. Equations were established to estimate multiple infections by single-pathogen detection. This revealed a linear correlation for pathogens in children with ARTIs. This study provides useful information for improving case prevention and management.",2015 Mar 9,"['Liu, Jia', 'Ai, Hongwu', 'Xiong, Ying', 'Li, Fu', 'Wen, Zhou', 'Liu, Weiyong', 'Li, Tongya', 'Qin, Kai', 'Wu, Jianguo', 'Liu, Yingle']",PLoS One,,,True
869eacf84d79a5b176e43988c2dea3be54f6b2ca,PMC,Survival of influenza A virus on contaminated student clothing,http://dx.doi.org/10.3892/etm.2015.2278,PMC4353734,25780410,CC BY,"The role of contaminated clothing in the transmission of influenza A virus during an epidemic period was investigated by examining the recovery of infectious influenza virus from experimentally virus-contaminated clothing, which had been subejected to routine wearing and washing for several months or years. The amount of infectious virus recovered from the nine types of clothing decreased with time and was shown to differ widely between clothing samples, when the contaminated clothing samples were maintained in uncovered glass Petri dishes in a safety cabinet under air blowing. These results indicate a dependence of virus transmissibility on the nature of the contaminated clothes. The difference in recovery was shown to have no significant correlation with the thickness or the materials of the clothing; however, a correlation was observed with the residual amount of water in the deposited virus preparation on the test clothing.",2015 Apr 9,"['IKEDA, KEIKO', 'TSUJIMOTO, KAZUKO', 'SUZUKI, YUKIKO', 'KOYAMA, AUGUSTINE HAJIME']",Exp Ther Med,,,True
2125de45b1af162d3500c2c33c85f33558a7c5e2,PMC,A Micropolymorphism Altering the Residue Triad 97/114/156 Determines the Relative Levels of Tapasin Independence and Distinct Peptide Profiles for HLA-A(*)24 Allotypes,http://dx.doi.org/10.1155/2014/298145,PMC4353853,25802875,CC BY,"While many HLA class I molecules interact directly with the peptide loading complex (PLC) for conventional loading of peptides certain class I molecules are able to present peptides in a way that circumvents the PLC components. We investigated micropolymorphisms at position 156 of HLA-A(*)24 allotypes and their effects on PLC dependence for assembly and peptide binding specificities. HLA-A(*)24:06(156Trp) and HLA-A(*)24:13(156Leu) showed high levels of cell surface expression while HLA-A(*)24:02(156Gln) was expressed at low levels in tapasin deficient cells. Peptides presented by these allelic variants showed distinct differences in features and repertoire. Immunoprecipitation experiments demonstrated all the HLA-A(*)24/156 variants to associate at similar levels with tapasin when present. Structurally, HLA-A(*)24:02 contains the residue triad Met97/His114/Gln156 and a Trp156 or Leu156 polymorphism provides tapasin independence by stabilizing these triad residues, thus generating an energetically stable and a more peptide receptive environment. Micropolymorphisms at position 156 can influence the generic peptide loading pathway for HLA-A(*)24 by altering their tapasin dependence for peptide selection. The trade-off for this tapasin independence could be the presentation of unusual ligands by these alleles, imposing significant risk following hematopoietic stem cell transplantation (HSCT).",2014 Dec 4,"['Badrinath, Soumya', 'Kunze-Schumacher, Heike', 'Blasczyk, Rainer', 'Huyton, Trevor', 'Bade-Doeding, Christina']",J Immunol Res,,,False
c08e4437d35ae6cdbeae2993e4a2264258f3431e,PMC,A Micropolymorphism Altering the Residue Triad 97/114/156 Determines the Relative Levels of Tapasin Independence and Distinct Peptide Profiles for HLA-A(*)24 Allotypes,http://dx.doi.org/10.1155/2014/298145,PMC4353853,25802875,CC BY,"While many HLA class I molecules interact directly with the peptide loading complex (PLC) for conventional loading of peptides certain class I molecules are able to present peptides in a way that circumvents the PLC components. We investigated micropolymorphisms at position 156 of HLA-A(*)24 allotypes and their effects on PLC dependence for assembly and peptide binding specificities. HLA-A(*)24:06(156Trp) and HLA-A(*)24:13(156Leu) showed high levels of cell surface expression while HLA-A(*)24:02(156Gln) was expressed at low levels in tapasin deficient cells. Peptides presented by these allelic variants showed distinct differences in features and repertoire. Immunoprecipitation experiments demonstrated all the HLA-A(*)24/156 variants to associate at similar levels with tapasin when present. Structurally, HLA-A(*)24:02 contains the residue triad Met97/His114/Gln156 and a Trp156 or Leu156 polymorphism provides tapasin independence by stabilizing these triad residues, thus generating an energetically stable and a more peptide receptive environment. Micropolymorphisms at position 156 can influence the generic peptide loading pathway for HLA-A(*)24 by altering their tapasin dependence for peptide selection. The trade-off for this tapasin independence could be the presentation of unusual ligands by these alleles, imposing significant risk following hematopoietic stem cell transplantation (HSCT).",2014 Dec 4,"['Badrinath, Soumya', 'Kunze-Schumacher, Heike', 'Blasczyk, Rainer', 'Huyton, Trevor', 'Bade-Doeding, Christina']",J Immunol Res,,,True
d708b6876813c3915edcbdda08c014d90ec694ab,PMC,Setting healthcare priorities in hospitals: a review of empirical studies,http://dx.doi.org/10.1093/heapol/czu010,PMC4353893,24604831,CC BY,"Priority setting research has focused on the macro (national) and micro (bedside) level, leaving the meso (institutional, hospital) level relatively neglected. This is surprising given the key role that hospitals play in the delivery of healthcare services and the large proportion of health systems resources that they absorb. To explore the factors that impact upon priority setting at the hospital level, we conducted a thematic review of empirical studies. A systematic search of PubMed, EBSCOHOST, Econlit databases and Google scholar was supplemented by a search of key websites and a manual search of relevant papers’ reference lists. A total of 24 papers were identified from developed and developing countries. We applied a policy analysis framework to examine and synthesize the findings of the selected papers. Findings suggest that priority setting practice in hospitals was influenced by (1) contextual factors such as decision space, resource availability, financing arrangements, availability and use of information, organizational culture and leadership, (2) priority setting processes that depend on the type of priority setting activity, (3) content factors such as priority setting criteria and (4) actors, their interests and power relations. We observe that there is need for studies to examine these issues and the interplay between them in greater depth and propose a conceptual framework that might be useful in examining priority setting practices in hospitals.",2015 Apr 5,"['Barasa, Edwine W', 'Molyneux, Sassy', 'English, Mike', 'Cleary, Susan']",Health Policy Plan,,,True
6a83b934090801454dc8e81a559ea4c20c0ef3c7,PMC,Setting healthcare priorities in hospitals: a review of empirical studies,http://dx.doi.org/10.1093/heapol/czu010,PMC4353893,24604831,CC BY,"Priority setting research has focused on the macro (national) and micro (bedside) level, leaving the meso (institutional, hospital) level relatively neglected. This is surprising given the key role that hospitals play in the delivery of healthcare services and the large proportion of health systems resources that they absorb. To explore the factors that impact upon priority setting at the hospital level, we conducted a thematic review of empirical studies. A systematic search of PubMed, EBSCOHOST, Econlit databases and Google scholar was supplemented by a search of key websites and a manual search of relevant papers’ reference lists. A total of 24 papers were identified from developed and developing countries. We applied a policy analysis framework to examine and synthesize the findings of the selected papers. Findings suggest that priority setting practice in hospitals was influenced by (1) contextual factors such as decision space, resource availability, financing arrangements, availability and use of information, organizational culture and leadership, (2) priority setting processes that depend on the type of priority setting activity, (3) content factors such as priority setting criteria and (4) actors, their interests and power relations. We observe that there is need for studies to examine these issues and the interplay between them in greater depth and propose a conceptual framework that might be useful in examining priority setting practices in hospitals.",2015 Apr 5,"['Barasa, Edwine W', 'Molyneux, Sassy', 'English, Mike', 'Cleary, Susan']",Health Policy Plan,,,False
af87680b269c20b507060a20c8dca7e986880e4c,PMC,Setting healthcare priorities in hospitals: a review of empirical studies,http://dx.doi.org/10.1093/heapol/czu010,PMC4353893,24604831,CC BY,"Priority setting research has focused on the macro (national) and micro (bedside) level, leaving the meso (institutional, hospital) level relatively neglected. This is surprising given the key role that hospitals play in the delivery of healthcare services and the large proportion of health systems resources that they absorb. To explore the factors that impact upon priority setting at the hospital level, we conducted a thematic review of empirical studies. A systematic search of PubMed, EBSCOHOST, Econlit databases and Google scholar was supplemented by a search of key websites and a manual search of relevant papers’ reference lists. A total of 24 papers were identified from developed and developing countries. We applied a policy analysis framework to examine and synthesize the findings of the selected papers. Findings suggest that priority setting practice in hospitals was influenced by (1) contextual factors such as decision space, resource availability, financing arrangements, availability and use of information, organizational culture and leadership, (2) priority setting processes that depend on the type of priority setting activity, (3) content factors such as priority setting criteria and (4) actors, their interests and power relations. We observe that there is need for studies to examine these issues and the interplay between them in greater depth and propose a conceptual framework that might be useful in examining priority setting practices in hospitals.",2015 Apr 5,"['Barasa, Edwine W', 'Molyneux, Sassy', 'English, Mike', 'Cleary, Susan']",Health Policy Plan,,,False
bdf348d6be154ebbd7acda6e7ff4ebcf66277708,PMC,Setting healthcare priorities in hospitals: a review of empirical studies,http://dx.doi.org/10.1093/heapol/czu010,PMC4353893,24604831,CC BY,"Priority setting research has focused on the macro (national) and micro (bedside) level, leaving the meso (institutional, hospital) level relatively neglected. This is surprising given the key role that hospitals play in the delivery of healthcare services and the large proportion of health systems resources that they absorb. To explore the factors that impact upon priority setting at the hospital level, we conducted a thematic review of empirical studies. A systematic search of PubMed, EBSCOHOST, Econlit databases and Google scholar was supplemented by a search of key websites and a manual search of relevant papers’ reference lists. A total of 24 papers were identified from developed and developing countries. We applied a policy analysis framework to examine and synthesize the findings of the selected papers. Findings suggest that priority setting practice in hospitals was influenced by (1) contextual factors such as decision space, resource availability, financing arrangements, availability and use of information, organizational culture and leadership, (2) priority setting processes that depend on the type of priority setting activity, (3) content factors such as priority setting criteria and (4) actors, their interests and power relations. We observe that there is need for studies to examine these issues and the interplay between them in greater depth and propose a conceptual framework that might be useful in examining priority setting practices in hospitals.",2015 Apr 5,"['Barasa, Edwine W', 'Molyneux, Sassy', 'English, Mike', 'Cleary, Susan']",Health Policy Plan,,,False
ad04f777044b7de892dbc174e31e88e63a160c3c,PMC,Aptamers in Diagnostics and Treatment of Viral Infections,http://dx.doi.org/10.3390/v7020751,PMC4353915,25690797,CC BY,"Aptamers are in vitro selected DNA or RNA molecules that are capable of binding a wide range of nucleic and non-nucleic acid molecules with high affinity and specificity. They have been conducted through the process known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment). It serves to reach specificity and considerable affinity to target molecules, including those of viral origin, both proteins and nucleic acids. Properties of aptamers allow detecting virus infected cells or viruses themselves and make them competitive to monoclonal antibodies. Specific aptamers can be used to interfere in each stage of the viral replication cycle and also inhibit its penetration into cells. Many current studies have reported possible application of aptamers as a treatment or diagnostic tool in viral infections, e.g., HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus), SARS (Severe Acute Respiratory Syndrome), H5N1 avian influenza and recently spread Ebola. This review presents current developments of using aptamers in the diagnostics and treatment of viral diseases.",2015 Feb 16,"['Wandtke, Tomasz', 'Woźniak, Joanna', 'Kopiński, Piotr']",Viruses,,,True
131902a67f5e00ae13b9239427325dfd53413349,PMC,Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection,http://dx.doi.org/10.3390/v7020798,PMC4353917,25690799,CC BY,"Respiratory syncytial virus (RSV) is the leading cause of pediatric viral respiratory tract infections. Neither vaccine nor effective antiviral therapy is available to prevent and treat RSV infection. Palivizumab, a humanized monoclonal antibody, is the only product approved to prevent serious RSV infection, but its high cost is prohibitive in low-income countries. Here, we aimed to identify an effective, safe, and affordable antiviral agent for pre-exposure prophylaxis (PrEP) of RSV infection in children at high risk. We found that maleic anhydride (ML)-modified human serum albumin (HSA), designated ML-HSA, exhibited potent antiviral activity against RSV and that the percentages of the modified lysines and arginies in ML- are correlated with such anti-RSV activity. ML-HSA inhibited RSV entry and replication by interacting with viral G protein and blocking RSV attachment to the target cells, while ML-HAS neither bound to F protein, nor inhibited F protein-mediated membrane fusion. Intranasal administration of ML-HSA before RSV infection resulted in significant decrease of the viral titers in the lungs of mice. ML-HSA shows promise for further development into an effective, safe, affordable, and easy-to-use intranasal regimen for pre-exposure prophylaxis of RSV infection in children at high risk in both low- and high-income countries.",2015 Feb 16,"['Sun, Zhiwu', 'Wang, Qian', 'Jia, Ran', 'Xia, Shuai', 'Li, Yuan', 'Liu, Qi', 'Xu, Wei', 'Xu, Jin', 'Du, Lanying', 'Lu, Lu', 'Jiang, Shibo']",Viruses,,,True
92f24acca725725852dd170c673f8adac4250faa,PMC,Development of Monoclonal Antibodies in China: Overview and Prospects,http://dx.doi.org/10.1155/2015/168935,PMC4355554,25811022,CC BY,"Monoclonal antibodies (mAbs) have become increasingly important as human therapeutic agents. Yet, current research concentrates on technology itself and pays attention to developed countries. This paper aims to provide a comprehensive review of mAbs development in China through systematic analysis of drug registry, patent applications, clinical trials, academic publication, and ongoing R&D projects. The trends in therapeutic areas and industrialization process are also highlighted. Development and research trends of mAbs are analyzed to provide a future perspective of mAbs as therapeutic agents in China.",2015 Feb 25,"['Zhang, Mao-Yu', 'Lu, Jin-Jian', 'Wang, Liang', 'Gao, Zi-Chao', 'Hu, Hao', 'Ung, Carolina Oi Lam', 'Wang, Yi-Tao']",Biomed Res Int,,,True
26d93683447b88c154664f5f80b35cd7991ba106,PMC,The Anti-Porcine Parvovirus Activity of Nanometer Propolis Flavone and Propolis Flavone In Vitro and In Vivo,http://dx.doi.org/10.1155/2015/472876,PMC4357139,25815034,CC BY,"Objectives. The present study was conducted to evaluate the activity of nanometer propolis flavone (NPF) on inhibiting porcine parvovirus (PPV) in vitro and in vivo. Methods. In vitro, the effect of NPF on cellular infectivity of PPV was carried out before and after adding drug and simultaneous adding and PPV after being mixed. In vivo, the anti-PPV effect of NPF in guinea pigs was performed. Results. The results showed that NPF could significantly inhibit PPV infecting porcine kidney- (PK-) 15 cells compared with propolis flavone (PF), and the activity of NPF was the best in preadding drug pattern. NPF at high and medium doses was able to observably restrain PPV copying in lung, gonad, blood, and spleen, decrease the impact of PPV on weight of guinea pigs, and improve hemagglutination inhibition (HI) of PPV in serum. In addition, it could also increase the contents of IL-2 and IL-6 in serum after PPV challenge. Conclusion. These results indicated that NPF could significantly improve the anti-PPV activity of PF, and its high concentration possessed the best efficacy. Therefore, NPF would be expected to be exploited into a new-style antiviral drug.",2015 Feb 26,"['Ma, Xia', 'Guo, Zhenhuan', 'Shen, Zhiqiang', 'Liu, Yonglu', 'Wang, Jinliang', 'Fan, Yunpeng']",Evid Based Complement Alternat Med,,,True
b7a6a987030c52cc7ecdf49c3933b6cfda488210,PMC,A systematic review and meta-analysis of the epidemiology of pathogenic Escherichia coli of calves and the role of calves as reservoirs for human pathogenic E. coli,http://dx.doi.org/10.3389/fcimb.2015.00023,PMC4357325,25815276,CC BY,"Escherichia coli bacteria are the most common causes of diarrhea and septicemia in calves. Moreover, calves form a major reservoir for transmission of pathogenic E. coli to humans. Systematic reviews and meta-analyses of publications on E. coli as calf pathogens and the role of calves as reservoir have not been done so far. We reviewed studies between 1951 and 2013 reporting the presence of virulence associated factors (VAFs) in calf E. coli and extracted the following information: year(s) and country of sampling, animal number, health status, isolate number, VAF prevalence, serotypes, diagnostic methods, and biological assays. The prevalence of VAFs or E. coli pathotypes was compared between healthy and diarrheic animals and was analyzed for time courses. Together, 106 papers with 25,982 E. coli isolates from 27 countries tested for VAFs were included. F5, F17, and F41 fimbriae and heat-stable enterotoxin (ST) – VAFs of enterotoxigenic E. coli (ETEC) were significantly associated with calf diarrhea. On the contrary, ETEC VAF F4 fimbriae and heat-labile enterotoxin as well as enteropathogenic (EPEC), Shiga toxin-producing (STEC), and enterohemorrhagic E. coli (EHEC) were not associated with diarrhea. The prevalence increased overtime for ST-positive isolates, but decreased for F5- and STEC-positive isolates. Our study provides useful information about the history of scientific investigations performed in this domain so far, and helps to define etiological agents of calf disease, and to evaluate calves as reservoir hosts for human pathogenic E. coli.",2015 Mar 12,"['Kolenda, Rafał', 'Burdukiewicz, Michał', 'Schierack, Peter']",Front Cell Infect Microbiol,,,True
c5b4fb9b393c9e5d24b075349fbb4601ea89c8f4,PMC,Good and Bad News about Ebola,http://dx.doi.org/10.1371/journal.pntd.0003509,PMC4357473,25764305,CC BY,,2015 Mar 12,"Peterson, A. Townsend",PLoS Negl Trop Dis,,,True
9f234fa9b0d6d7c0809106111104ad8843f3a931,PMC,Monitoring Disease Trends using Hospital Traffic Data from High Resolution Satellite Imagery: A Feasibility Study,http://dx.doi.org/10.1038/srep09112,PMC4357853,25765943,CC BY,"Challenges with alternative data sources for disease surveillance include differentiating the signal from the noise, and obtaining information from data constrained settings. For the latter, events such as increases in hospital traffic could serve as early indicators of social disruption resulting from disease. In this study, we evaluate the feasibility of using hospital parking lot traffic data extracted from high-resolution satellite imagery to augment public health disease surveillance in Chile, Argentina and Mexico. We used archived satellite imagery collected from January 2010 to May 2013 and data on the incidence of respiratory virus illnesses from the Pan American Health Organization as a reference. We developed dynamical Elastic Net multivariable linear regression models to estimate the incidence of respiratory virus illnesses using hospital traffic and assessed how to minimize the effects of noise on the models. We noted that predictions based on models fitted using a sample of observations were better. The results were consistent across countries with selected models having reasonably low normalized root-mean-squared errors and high correlations for both the fits and predictions. The observations from this study suggest that if properly procured and combined with other information, this data source could be useful for monitoring disease trends.",2015 Mar 13,"['Nsoesie, Elaine O.', 'Butler, Patrick', 'Ramakrishnan, Naren', 'Mekaru, Sumiko R.', 'Brownstein, John S.']",Sci Rep,,,True
47379741a7a89589b8870290e5224096202f56fd,PMC,Monitoring Disease Trends using Hospital Traffic Data from High Resolution Satellite Imagery: A Feasibility Study,http://dx.doi.org/10.1038/srep09112,PMC4357853,25765943,CC BY,"Challenges with alternative data sources for disease surveillance include differentiating the signal from the noise, and obtaining information from data constrained settings. For the latter, events such as increases in hospital traffic could serve as early indicators of social disruption resulting from disease. In this study, we evaluate the feasibility of using hospital parking lot traffic data extracted from high-resolution satellite imagery to augment public health disease surveillance in Chile, Argentina and Mexico. We used archived satellite imagery collected from January 2010 to May 2013 and data on the incidence of respiratory virus illnesses from the Pan American Health Organization as a reference. We developed dynamical Elastic Net multivariable linear regression models to estimate the incidence of respiratory virus illnesses using hospital traffic and assessed how to minimize the effects of noise on the models. We noted that predictions based on models fitted using a sample of observations were better. The results were consistent across countries with selected models having reasonably low normalized root-mean-squared errors and high correlations for both the fits and predictions. The observations from this study suggest that if properly procured and combined with other information, this data source could be useful for monitoring disease trends.",2015 Mar 13,"['Nsoesie, Elaine O.', 'Butler, Patrick', 'Ramakrishnan, Naren', 'Mekaru, Sumiko R.', 'Brownstein, John S.']",Sci Rep,,,False
341fd3d94baafcde2e5e7c0b1d166028d69523e4,PMC,FDA approved drugs as potential Ebola treatments,http://dx.doi.org/10.12688/f1000research.6164.2,PMC4358410,25789163,CC BY,"In the search for treatments for the Ebola Virus, multiple screens of FDA drugs have led to the identification of several with promising in vitro activity. These compounds were not originally developed as antivirals and some have been further tested in mouse in vivo models. We put forward the opinion that some of these drugs could be evaluated further and move into the clinic as they are already FDA approved and in many cases readily available. This may be important if there is a further outbreak in future and no other therapeutic is available.",2015 Mar 10,"['Ekins, Sean', 'Coffee, Megan']",F1000Res,,,True
241bbd33b32abf0cc6adb68b9c80381f0856cddd,PMC,Impact of Porcine Epidemic Diarrhea on Performance of Growing Pigs,http://dx.doi.org/10.1371/journal.pone.0120532,PMC4359118,25768287,CC BY,"The impact of porcine epidemic diarrhea virus (PEDv) infection on the US pork industry has mainly been attributed to the mortality that it causes in suckling piglets, and, consequently, much effort has been invested in the quantification of its effect in sow farms. However, no information on the performance of surviving pigs that were exposed to the PEDv as piglets is available. Here, a retrospective cohort study to evaluate the impact of porcine epidemic diarrhea virus (PEDv) infection on growing pigs’ performance, as indicated by mortality, average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) was performed using production records from weaned pigs in nursery and wean-to-finish sites from sow farms that became PEDv-infected between May 2013 and June 2014. Production records from the first batch of growing pigs weaned in infected flows after the PEDv outbreak (“infected batches”) were compared with those from pigs weaned within the previous 14 to 120 days (“control batches”). Performance records from infected and control batches, paired by flow, were compared using non-parametric paired tests. Mortality, ADG and FCR were significantly different in PEDv-positive (infected) compared with PEDv-negative (control) batches, with a mean increase of mortality and FCR of 11% and 0.5, respectively, and a decrease of ADG of 0.16 lb/day. Our results demonstrate a poorer performance of growing pigs weaned after a PEDv outbreak compared with those weaned within the previous 14-120 days, suggesting that in addition to the mortality induced by PEDv in suckling pigs, the disease also impairs the performance of surviving pig. These findings help to quantify the impact of PEDv infection in the US and, ultimately, contribute to efforts to quantify the cost-effectiveness of disease prevention and control measures.",2015 Mar 13,"['Alvarez, Julio', 'Sarradell, Javier', 'Morrison, Robert', 'Perez, Andres']",PLoS One,,,True
78fb5545880b83bbbef7058bf5c99ff618b35f7b,PMC,Molecular epidemiological study of feline coronavirus strains in Japan using RT-PCR targeting nsp14 gene,http://dx.doi.org/10.1186/s12917-015-0372-2,PMC4359392,25889235,CC BY,"BACKGROUND: Feline infectious peritonitis is a fatal disease of cats caused by infection with feline coronavirus (FCoV). For detecting or genotyping of FCoV, some RT-PCR plus nested PCR techniques have been reported previously. However, referring to the whole genome sequences (WGSs) registered at NCBI, there are no detection methods that can tolerate the genetic diversity among FCoV population. In addition, the quasispecies nature of FCoV, which consists of heterogeneous variants, has been also demonstrated; thus, a universal method for heteropopulations of FCoV variants in clinical specimens is desirable. RESULTS: To develop an RT-PCR method for detection and genotyping of FCoV, we performed comparative genome analysis using WGSs of 32 FCoV, 7 CCoV and 5 TGEV strains obtained from NCBI. As the PCR target, we focused on the nsp14 coding region, which is highly conserved and phylogenetically informative, and developed a PCR method targeting nsp14 partial sequences. Among 103 ascites, 45 pleural effusion and 214 blood specimens from clinically ill cats, we could detect FCoV in 55 (53.4%), 14 (31.1%) and 19 (8.9%) specimens using the present method. Direct sequencing of PCR products and phylogenetic analysis allowed discrimination between type I- and II-FCoV serotypes. Our nsp14 amino acid sequence typing (nsp14 aa ST) showed that the FCoV clone with sequence type (ST) 42, which was the most predominant genotype of WGS strains, was prevalent in domestic cats in Japan. CONCLUSIONS: Our nsp14 PCR scheme will contribute to virus detection, epidemiology and ecology of FCoV strains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0372-2) contains supplementary material, which is available to authorized users.",2015 Mar 11,"['Tanaka, Yoshikazu', 'Sasaki, Takashi', 'Matsuda, Ryo', 'Uematsu, Yosuke', 'Yamaguchi, Tomohiro']",BMC Vet Res,,,True
1904cb0e767c673c78ac5d6ebf6260c1d83bea13,PMC,Hematopoietic Cancer Cell Lines Can Support Replication of Sabin Poliovirus Type 1,http://dx.doi.org/10.1155/2015/358462,PMC4359862,25815312,CC BY,"Viral vaccines can be produced in adherent or in suspension cells. The objective of this work was to screen human suspension cell lines for the capacity to support viral replication. As the first step, it was investigated whether poliovirus can replicate in such cell lines. Sabin poliovirus type 1 was serially passaged on five human cell lines, HL60, K562, KG1, THP-1, and U937. Sabin type 1 was capable of efficiently replicating in three cell lines (K562, KG1, and U937), yielding high viral titers after replication. Expression of CD155, the poliovirus receptor, did not explain susceptibility to replication, since all cell lines expressed CD155. Furthermore, we showed that passaged virus replicated more efficiently than parental virus in KG1 cells, yielding higher virus titers in the supernatant early after infection. Infection of cell lines at an MOI of 0.01 resulted in high viral titers in the supernatant at day 4. Infection of K562 with passaged Sabin type 1 in a bioreactor system yielded high viral titers in the supernatant. Altogether, these data suggest that K562, KG1, and U937 cell lines are useful for propagation of poliovirus.",2015 Feb 28,"['Oosterhoff, Dinja', 'van de Weerd, Gerard', 'van Eikenhorst, Gerco', 'de Gruijl, Tanja D.', 'van der Pol, Leo A.', 'Bakker, Wilfried A. M.']",Biomed Res Int,,,True
f76b1d637fdb9e5d6a32d1a6d3804a2acb9f0f23,PMC,The prevention and eradication of smallpox: a commentary on Sloane (1755) ‘An account of inoculation’,http://dx.doi.org/10.1098/rstb.2014.0378,PMC4360126,25750241,CC BY,"Sir Hans Sloane's account of inoculation as a means to protect against smallpox followed several earlier articles published in Philosophical Transactions on this procedure. Inoculation (also called ‘variolation’) involved the introduction of small amounts of infectious material from smallpox vesicles into the skin of healthy subjects, with the goal of inducing mild symptoms that would result in protection against the more severe naturally acquired disease. It began to be practised in England in 1721 thanks to the efforts of Lady Mary Wortley Montagu who influenced Sloane to promote its use, including the inoculation of the royal family's children. When Edward Jenner's inoculation with the cow pox (‘vaccination’) followed 75 years later as a safer yet equally effective procedure, the scene was set for the eventual control of smallpox epidemics culminating in the worldwide eradication of smallpox in 1977, officially proclaimed by WHO in 1980. Here, we discuss the significance of variolation and vaccination with respect to scientific, public health and ethical controversies concerning these ‘weapons of mass protection’. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.",2015 Apr 19,"['Weiss, Robin A.', 'Esparza, José']",Philos Trans R Soc Lond B Biol Sci,,,True
d469f2e82c820caea8ab2d4f92b7a5a93a23f569,PMC,"Risk Factors for Death from Influenza A(H1N1)pdm09, State of São Paulo, Brazil, 2009",http://dx.doi.org/10.1371/journal.pone.0118772,PMC4361171,25774804,CC BY,"This case-control study aimed to assess the risk factors for death from influenza A(H1N1)pdm09 in patients with laboratory confirmation, who had severe acute respiratory illness-SARI and were hospitalized between June 28(th) and August 29(th) 2009, in the metropolitan regions of São Paulo and Campinas, Brazil. Medical charts of all the 193 patients who died (cases) and the 386 randomly selected patients who recovered (controls) were investigated in 177 hospitals. Household interviews were conducted with those who had survived and the closest relative of those who had died. 73.6% of cases and 38.1% of controls were at risk of developing influenza-related complications. The 18-to-59-year age group (OR = 2.31, 95%CI: 1.31–4.10 (reference up to 18 years of age)), presence of risk conditions for severity of influenza (OR = 1.99, 95%CI: 1.11–3.57, if one or OR = 6.05, 95%CI: 2.76–13.28, if more than one), obesity (OR = 2.73, 95%CI: 1.28–5.83), immunosuppression (OR = 3.43, 95%CI: 1.28–9.19), and search for previous care associated with the hospitalization (OR = 3.35, 95%CI: 1.75–6.40) were risk factors for death. Antiviral treatment performed within 72 hours of the onset of symptoms (OR = 0.17, 95%CI: 0.08–0.37, if within 48hours, and OR = 0.30, 95%CI: 0.11–0.81, if between 48 and 72 hours) was protective against death. The identification of high-risk patients and early treatment are important factors for reducing morbi-mortality from influenza.",2015 Mar 16,"['Ribeiro, Ana Freitas', 'Pellini, Alessandra Cristina Guedes', 'Kitagawa, Beatriz Yuko', 'Marques, Daniel', 'Madalosso, Geraldine', 'de Cassia Nogueira Figueira, Gerrita', 'Fred, João', 'Albernaz, Ricardo Kerti Mangabeira', 'Carvalhanas, Telma Regina Marques Pinto', 'Zanetta, Dirce Maria Trevisan']",PLoS One,,,True
364b968c148ee72c7336bf89c06974a646683fd3,PMC,Xenosurveillance: A Novel Mosquito-Based Approach for Examining the Human-Pathogen Landscape,http://dx.doi.org/10.1371/journal.pntd.0003628,PMC4361501,25775236,CC0,"BACKGROUND: Globally, regions at the highest risk for emerging infectious diseases are often the ones with the fewest resources. As a result, implementing sustainable infectious disease surveillance systems in these regions is challenging. The cost of these programs and difficulties associated with collecting, storing and transporting relevant samples have hindered them in the regions where they are most needed. Therefore, we tested the sensitivity and feasibility of a novel surveillance technique called xenosurveillance. This approach utilizes the host feeding preferences and behaviors of Anopheles gambiae, which are highly anthropophilic and rest indoors after feeding, to sample viruses in human beings. We hypothesized that mosquito bloodmeals could be used to detect vertebrate viral pathogens within realistic field collection timeframes and clinically relevant concentrations. METHODOLOGY/PRINCIPAL FINDINGS: To validate this approach, we examined variables influencing virus detection such as the duration between mosquito blood feeding and mosquito processing, the pathogen nucleic acid stability in the mosquito gut and the pathogen load present in the host’s blood at the time of bloodmeal ingestion using our laboratory model. Our findings revealed that viral nucleic acids, at clinically relevant concentrations, could be detected from engorged mosquitoes for up to 24 hours post feeding by qRT-PCR. Subsequently, we tested this approach in the field by examining blood from engorged mosquitoes from two field sites in Liberia. Using next-generation sequencing and PCR we were able to detect the genetic signatures of multiple viral pathogens including Epstein-Barr virus and canine distemper virus. CONCLUSIONS/SIGNIFICANCE: Together, these data demonstrate the feasibility of xenosurveillance and in doing so validated a simple and non-invasive surveillance tool that could be used to complement current biosurveillance efforts.",2015 Mar 16,"['Grubaugh, Nathan D.', 'Sharma, Supriya', 'Krajacich, Benjamin J.', 'Fakoli III, Lawrence S.', 'Bolay, Fatorma K.', 'Diclaro II, Joe W.', 'Johnson, W. Evan', 'Ebel, Gregory D.', 'Foy, Brian D.', 'Brackney, Doug E.']",PLoS Negl Trop Dis,,,True
6ce5b9aac3338153eaf845252d28c3f06a0fb014,PMC,Adenovirus and Herpesvirus Diversity in Free-Ranging Great Apes in the Sangha Region of the Republic of Congo,http://dx.doi.org/10.1371/journal.pone.0118543,PMC4362762,25781992,CC BY,"Infectious diseases have caused die-offs in both free-ranging gorillas and chimpanzees. Understanding pathogen diversity and disease ecology is therefore critical for conserving these endangered animals. To determine viral diversity in free-ranging, non-habituated gorillas and chimpanzees in the Republic of Congo, genetic testing was performed on great-ape fecal samples collected near Odzala-Kokoua National Park. Samples were analyzed to determine ape species, identify individuals in the population, and to test for the presence of herpesviruses, adenoviruses, poxviruses, bocaviruses, flaviviruses, paramyxoviruses, coronaviruses, filoviruses, and simian immunodeficiency virus (SIV). We identified 19 DNA viruses representing two viral families, Herpesviridae and Adenoviridae, of which three herpesviruses had not been previously described. Co-detections of multiple herpesviruses and/or adenoviruses were present in both gorillas and chimpanzees. Cytomegalovirus (CMV) and lymphocryptovirus (LCV) were found primarily in the context of co-association with each other and adenoviruses. Using viral discovery curves for herpesviruses and adenoviruses, the total viral richness in the sample population of gorillas and chimpanzees was estimated to be a minimum of 23 viruses, corresponding to a detection rate of 83%. These findings represent the first description of DNA viral diversity in feces from free-ranging gorillas and chimpanzees in or near the Odzala-Kokoua National Park and form a basis for understanding the types of viruses circulating among great apes in this region.",2015 Mar 17,"['Seimon, Tracie A.', 'Olson, Sarah H.', 'Lee, Kerry Jo', 'Rosen, Gail', 'Ondzie, Alain', 'Cameron, Kenneth', 'Reed, Patricia', 'Anthony, Simon J.', 'Joly, Damien O.', 'McAloose, Denise', 'Lipkin, W. Ian']",PLoS One,,,True
cf8e39bf81b1e6e273adf55fb5db2245bd8bc885,PMC,The Porcine MicroRNA Transcriptome Response to Transmissible Gastroenteritis Virus Infection,http://dx.doi.org/10.1371/journal.pone.0120377,PMC4363316,25781021,CC BY,"Transmissible gastroenteritis virus (TGEV; Coronaviridae family) causes huge economic losses to the swine industry. MicroRNAs (miRNAs) play a regulatory role in viral infection and may be involved in the mammalian immune response. Here, we report a comprehensive analysis of host miRNA expression in TGEV-infected swine testis (ST) cells. Deep sequencing generated 3,704,353 and 2,763,665 reads from uninfected ST cells and infected ST cells, respectively. The reads were aligned to known Sus scrofa pre-miRNAs in miRBase 19, identifying 284 annotated miRNAs. Certain miRNAs were differentially regulated during TGEV infection. 59 unique miRNAs displayed significant differentially expression between the normal and TGEV-infected ST cell samples: 15 miRNAs were significantly up-regulated and 44 were significantly down-regulated. Stem-loop RT-PCR was carried out to determine the expression levels of specific miRNAs in the two samples, and the results were consistent with those of sequencing. Gene ontology enrichment analysis of host target genes demonstrated that the differentially expressed miRNAs are involved in regulatory networks, including cellular process, metabolic process, immune system process. This is the first report of the identification of ST cell miRNAs and the comprehensive analysis of the miRNA regulatory mechanism during TGEV infection, which revealed the miRNA molecular regulatory mechanisms for the viral infection, expression of viral genes and the expression of immune-related genes. The results presented here will aid research on the prevention and treatment of viral diseases.",2015 Mar 17,"['Liu, Xiao', 'Zhu, Ling', 'Liao, Shan', 'Xu, Zhiwen', 'Zhou, Yuancheng']",PLoS One,,,True
97d1af515c43a768c3b46d22e69a2bcddd764ceb,PMC,The Porcine MicroRNA Transcriptome Response to Transmissible Gastroenteritis Virus Infection,http://dx.doi.org/10.1371/journal.pone.0120377,PMC4363316,25781021,CC BY,"Transmissible gastroenteritis virus (TGEV; Coronaviridae family) causes huge economic losses to the swine industry. MicroRNAs (miRNAs) play a regulatory role in viral infection and may be involved in the mammalian immune response. Here, we report a comprehensive analysis of host miRNA expression in TGEV-infected swine testis (ST) cells. Deep sequencing generated 3,704,353 and 2,763,665 reads from uninfected ST cells and infected ST cells, respectively. The reads were aligned to known Sus scrofa pre-miRNAs in miRBase 19, identifying 284 annotated miRNAs. Certain miRNAs were differentially regulated during TGEV infection. 59 unique miRNAs displayed significant differentially expression between the normal and TGEV-infected ST cell samples: 15 miRNAs were significantly up-regulated and 44 were significantly down-regulated. Stem-loop RT-PCR was carried out to determine the expression levels of specific miRNAs in the two samples, and the results were consistent with those of sequencing. Gene ontology enrichment analysis of host target genes demonstrated that the differentially expressed miRNAs are involved in regulatory networks, including cellular process, metabolic process, immune system process. This is the first report of the identification of ST cell miRNAs and the comprehensive analysis of the miRNA regulatory mechanism during TGEV infection, which revealed the miRNA molecular regulatory mechanisms for the viral infection, expression of viral genes and the expression of immune-related genes. The results presented here will aid research on the prevention and treatment of viral diseases.",2015 Mar 17,"['Liu, Xiao', 'Zhu, Ling', 'Liao, Shan', 'Xu, Zhiwen', 'Zhou, Yuancheng']",PLoS One,,,False
059c5688c0caf75bf1d1532a7d36230247599064,PMC,The Porcine MicroRNA Transcriptome Response to Transmissible Gastroenteritis Virus Infection,http://dx.doi.org/10.1371/journal.pone.0120377,PMC4363316,25781021,CC BY,"Transmissible gastroenteritis virus (TGEV; Coronaviridae family) causes huge economic losses to the swine industry. MicroRNAs (miRNAs) play a regulatory role in viral infection and may be involved in the mammalian immune response. Here, we report a comprehensive analysis of host miRNA expression in TGEV-infected swine testis (ST) cells. Deep sequencing generated 3,704,353 and 2,763,665 reads from uninfected ST cells and infected ST cells, respectively. The reads were aligned to known Sus scrofa pre-miRNAs in miRBase 19, identifying 284 annotated miRNAs. Certain miRNAs were differentially regulated during TGEV infection. 59 unique miRNAs displayed significant differentially expression between the normal and TGEV-infected ST cell samples: 15 miRNAs were significantly up-regulated and 44 were significantly down-regulated. Stem-loop RT-PCR was carried out to determine the expression levels of specific miRNAs in the two samples, and the results were consistent with those of sequencing. Gene ontology enrichment analysis of host target genes demonstrated that the differentially expressed miRNAs are involved in regulatory networks, including cellular process, metabolic process, immune system process. This is the first report of the identification of ST cell miRNAs and the comprehensive analysis of the miRNA regulatory mechanism during TGEV infection, which revealed the miRNA molecular regulatory mechanisms for the viral infection, expression of viral genes and the expression of immune-related genes. The results presented here will aid research on the prevention and treatment of viral diseases.",2015 Mar 17,"['Liu, Xiao', 'Zhu, Ling', 'Liao, Shan', 'Xu, Zhiwen', 'Zhou, Yuancheng']",PLoS One,,,False
f13019c1409c978d7d11cdbbbb4b2c16abfc1bd7,PMC,Network-based analysis of comorbidities risk during an infection: SARS and HIV case studies,http://dx.doi.org/10.1186/1471-2105-15-333,PMC4363349,25344230,CC BY,"BACKGROUND: Infections are often associated to comorbidity that increases the risk of medical conditions which can lead to further morbidity and mortality. SARS is a threat which is similar to MERS virus, but the comorbidity is the key aspect to underline their different impacts. One UK doctor says ""I’d rather have HIV than diabetes"" as life expectancy among diabetes patients is lower than that of HIV. However, HIV has a comorbidity impact on the diabetes. RESULTS: We present a quantitative framework to compare and explore comorbidity between diseases. By using neighbourhood based benchmark and topological methods, we have built comorbidity relationships network based on the OMIM and our identified significant genes. Then based on the gene expression, PPI and signalling pathways data, we investigate the comorbidity association of these 2 infective pathologies with other 7 diseases (heart failure, kidney disorder, breast cancer, neurodegenerative disorders, bone diseases, Type 1 and Type 2 diabetes). Phenotypic association is measured by calculating both the Relative Risk as the quantified measures of comorbidity tendency of two disease pairs and the ϕ-correlation to measure the robustness of the comorbidity associations. The differential gene expression profiling strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response and statistically dysregulates a large number of genes, pathways and PPIs subnetworks in different pathologies such as chronic heart failure (21 genes), breast cancer (16 genes) and bone diseases (11 genes). HIV-1 induces comorbidities relationship with many other diseases, particularly strong correlation with the neurological, cancer, metabolic and immunological diseases. Similar comorbidities risk is observed from the clinical information. Moreover, SARS and HIV infections dysregulate 4 genes (ANXA3, GNS, HIST1H1C, RASA3) and 3 genes (HBA1, TFRC, GHITM) respectively that affect the ageing process. It is notable that HIV and SARS similarly dysregulated 11 genes and 3 pathways. Only 4 significantly dysregulated genes are common between SARS-CoV and MERS-CoV, including NFKBIA that is a key regulator of immune responsiveness implicated in susceptibility to infectious and inflammatory diseases. CONCLUSIONS: Our method presents a ripe opportunity to use data-driven approaches for advancing our current knowledge on disease mechanism and predicting disease comorbidities in a quantitative way. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-333) contains supplementary material, which is available to authorized users.",2014 Oct 24,"['Moni, Mohammad Ali', 'Liò, Pietro']",BMC Bioinformatics,,,False
f83277cbba652f6ef2a9893a3d470cdf6580979d,PMC,Network-based analysis of comorbidities risk during an infection: SARS and HIV case studies,http://dx.doi.org/10.1186/1471-2105-15-333,PMC4363349,25344230,CC BY,"BACKGROUND: Infections are often associated to comorbidity that increases the risk of medical conditions which can lead to further morbidity and mortality. SARS is a threat which is similar to MERS virus, but the comorbidity is the key aspect to underline their different impacts. One UK doctor says ""I’d rather have HIV than diabetes"" as life expectancy among diabetes patients is lower than that of HIV. However, HIV has a comorbidity impact on the diabetes. RESULTS: We present a quantitative framework to compare and explore comorbidity between diseases. By using neighbourhood based benchmark and topological methods, we have built comorbidity relationships network based on the OMIM and our identified significant genes. Then based on the gene expression, PPI and signalling pathways data, we investigate the comorbidity association of these 2 infective pathologies with other 7 diseases (heart failure, kidney disorder, breast cancer, neurodegenerative disorders, bone diseases, Type 1 and Type 2 diabetes). Phenotypic association is measured by calculating both the Relative Risk as the quantified measures of comorbidity tendency of two disease pairs and the ϕ-correlation to measure the robustness of the comorbidity associations. The differential gene expression profiling strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response and statistically dysregulates a large number of genes, pathways and PPIs subnetworks in different pathologies such as chronic heart failure (21 genes), breast cancer (16 genes) and bone diseases (11 genes). HIV-1 induces comorbidities relationship with many other diseases, particularly strong correlation with the neurological, cancer, metabolic and immunological diseases. Similar comorbidities risk is observed from the clinical information. Moreover, SARS and HIV infections dysregulate 4 genes (ANXA3, GNS, HIST1H1C, RASA3) and 3 genes (HBA1, TFRC, GHITM) respectively that affect the ageing process. It is notable that HIV and SARS similarly dysregulated 11 genes and 3 pathways. Only 4 significantly dysregulated genes are common between SARS-CoV and MERS-CoV, including NFKBIA that is a key regulator of immune responsiveness implicated in susceptibility to infectious and inflammatory diseases. CONCLUSIONS: Our method presents a ripe opportunity to use data-driven approaches for advancing our current knowledge on disease mechanism and predicting disease comorbidities in a quantitative way. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-333) contains supplementary material, which is available to authorized users.",2014 Oct 24,"['Moni, Mohammad Ali', 'Liò, Pietro']",BMC Bioinformatics,,,False
092193fe026d59729062786d8f576b553e11a97d,PMC,Network-based analysis of comorbidities risk during an infection: SARS and HIV case studies,http://dx.doi.org/10.1186/1471-2105-15-333,PMC4363349,25344230,CC BY,"BACKGROUND: Infections are often associated to comorbidity that increases the risk of medical conditions which can lead to further morbidity and mortality. SARS is a threat which is similar to MERS virus, but the comorbidity is the key aspect to underline their different impacts. One UK doctor says ""I’d rather have HIV than diabetes"" as life expectancy among diabetes patients is lower than that of HIV. However, HIV has a comorbidity impact on the diabetes. RESULTS: We present a quantitative framework to compare and explore comorbidity between diseases. By using neighbourhood based benchmark and topological methods, we have built comorbidity relationships network based on the OMIM and our identified significant genes. Then based on the gene expression, PPI and signalling pathways data, we investigate the comorbidity association of these 2 infective pathologies with other 7 diseases (heart failure, kidney disorder, breast cancer, neurodegenerative disorders, bone diseases, Type 1 and Type 2 diabetes). Phenotypic association is measured by calculating both the Relative Risk as the quantified measures of comorbidity tendency of two disease pairs and the ϕ-correlation to measure the robustness of the comorbidity associations. The differential gene expression profiling strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response and statistically dysregulates a large number of genes, pathways and PPIs subnetworks in different pathologies such as chronic heart failure (21 genes), breast cancer (16 genes) and bone diseases (11 genes). HIV-1 induces comorbidities relationship with many other diseases, particularly strong correlation with the neurological, cancer, metabolic and immunological diseases. Similar comorbidities risk is observed from the clinical information. Moreover, SARS and HIV infections dysregulate 4 genes (ANXA3, GNS, HIST1H1C, RASA3) and 3 genes (HBA1, TFRC, GHITM) respectively that affect the ageing process. It is notable that HIV and SARS similarly dysregulated 11 genes and 3 pathways. Only 4 significantly dysregulated genes are common between SARS-CoV and MERS-CoV, including NFKBIA that is a key regulator of immune responsiveness implicated in susceptibility to infectious and inflammatory diseases. CONCLUSIONS: Our method presents a ripe opportunity to use data-driven approaches for advancing our current knowledge on disease mechanism and predicting disease comorbidities in a quantitative way. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-333) contains supplementary material, which is available to authorized users.",2014 Oct 24,"['Moni, Mohammad Ali', 'Liò, Pietro']",BMC Bioinformatics,,,True
963a2753dda05c4a8a3a67d725477f4b7c5aa850,PMC,A reach-out system for video microscopy analysis of ciliary motions aiding PCD diagnosis,http://dx.doi.org/10.1186/s13104-015-0999-x,PMC4363456,25869032,CC BY,"BACKGROUNDS: High-speed Video-Microscopy Analysis (HVMA) is now being used to aid diagnosis of Primary Ciliary Dyskinesia (PCD). Only a few centers however, are equipped with the available resources and equipment to perform these tests. We describe our experience in HVMA reaching-out to many more peripheral and relatively remote areas. A portable computer with HVMA software, video camera and a microscope were used. Fourteen disperse pediatric centers were reached and a total of 203 subjects were tested within a relatively short time (Clinical Trial Registration: NCT 01070914 (registered February 6, 2010). RESULTS: With an average time of 20 minutes per patient, the system enabled us to test approximately 10–15 subjects per day. A valid HVMA result was made in 148 subjects and helped in the diagnosis of PCD in many of the patients who were subsequently confirmed to have PCD by electron microscopy and/or immunofluoresence and/or genetics and/or nasal Nitric Oxide testing. The sensitivity of abnormal HVMA to accurately predict PCD was 90.2%. DISCUSSION AND CONCLUSION: This is the first report of an out-reach system to record HVMA for improved diagnosis of PCD in remote regions that are not within reach of PCD centers and experts. It provides immediate preliminary results and instantaneous feedback to the physician, patient and his/her family members in these areas. Future studies to compare this system to conventional desk top systems are warranted. TRIAL REGISTRATION: NCT 01070914 (registered February 6, 2010).",2015 Mar 8,"['Amirav, Israel', 'Mussaffi, Huda', 'Roth, Yehudah', 'Schmidts, Miriam', 'Omran, Heymut', 'Werner, Claudius', None]",BMC Res Notes,,,True
824c9c7d7d8c1ec672e85def94cee3bb471cb5a0,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,True
d834c2a0c2e05777cf880d4f546ec97b062dcc42,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
2c04da72ce976795940e38e9a90e611c0c77b31e,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
e1b6c87bdaddd991a59b81a5e26c733a969a2966,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
fe283ded17eb6226b2d32e35d404810a1ba71a56,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
c2e00330921ce0f4e7d51acfc4563f89c235fe1a,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
62f22f970324e86bd0345b6d8bda6bc3a8dcb510,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
91324428bbd7efaf1a962e1ddfd2910df88421ec,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
6e5c9a3ed6c345b60a8487db57e1113331a11749,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
bc8a110db0d7d8689a85e6ecf572e072854fa59e,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
64d06661271ec6b071977aad4a76e0703afad1f8,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
fcd4c77a9251d6bb55ac8d66f1b1a29977f9d25a,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
f3a8d18c230ff34d3bde488f8db9c82f6b11fe6b,PMC,Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa,http://dx.doi.org/10.1371/journal.pntd.0003631,PMC4363514,25781465,CC BY,"Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.",2015 Mar 17,"['Stremlau, Matthew H.', 'Andersen, Kristian G.', 'Folarin, Onikepe A.', 'Grove, Jessica N.', 'Odia, Ikponmwonsa', 'Ehiane, Philomena E.', 'Omoniwa, Omowunmi', 'Omoregie, Omigie', 'Jiang, Pan-Pan', 'Yozwiak, Nathan L.', 'Matranga, Christian B.', 'Yang, Xiao', 'Gire, Stephen K.', 'Winnicki, Sarah', 'Tariyal, Ridhi', 'Schaffner, Stephen F.', 'Okokhere, Peter O.', 'Okogbenin, Sylvanus', 'Akpede, George O.', 'Asogun, Danny A.', 'Agbonlahor, Dennis E.', 'Walker, Peter J.', 'Tesh, Robert B.', 'Levin, Joshua Z.', 'Garry, Robert F.', 'Sabeti, Pardis C.', 'Happi, Christian T.']",PLoS Negl Trop Dis,,,False
bef152d3ffbf6d9d35ae91a54f1eb447e18d7543,PMC,The Relationship of CSF and Plasma Cytokine Levels in HIV Infected Patients with Neurocognitive Impairment,http://dx.doi.org/10.1155/2015/506872,PMC4363531,25821806,CC BY,"Although HAD is now rare due to HAART, the milder forms of HAND persist in HIV-infected patients. HIV-induced systemic and localized inflammation is considered to be one of the mechanisms of HAND. The levels of cytokines in CSF were associated with neurocognitive impairment in HIV infection. However, the changes of cytokines involved in cognition impairment in plasma have not been shown, and their relationships between CSF and plasma require to be addressed. We compared cytokine levels in paired CSF and plasma samples from HIV-infected individuals with or without neurocognitive impairment. Cytokine concentrations were measured by Luminex xMAP. In comparing the expression levels of cytokines in plasma and CSF, IFN-α2, IL-8, IP-10, and MCP-1 were significantly higher in CSF. Eotaxin was significantly higher in plasma, whereas G-CSF showed no difference between plasma and CSF. G-CSF (P = 0.0079), IL-8 (P = 0.0223), IP-10 (P = 0.0109), and MCP-1 (P = 0.0497) in CSF showed significant difference between HIV-CI and HIV-NC group, which may indicate their relationship to HIV associated neurocognitive impairment. In addition, G-CSF (P = 0.0191) and IP-10 (P = 0.0377) in plasma were significantly higher in HIV-CI than HIV-NC. The consistent changes of G-CSF and IP-10 in paired plasma and CSF samples might enhance their potential for predicting HAND.",2015 Mar 3,"['Yuan, Lin', 'Liu, An', 'Qiao, Luxin', 'Sheng, Bo', 'Xu, Meng', 'Li, Wei', 'Chen, Dexi']",Biomed Res Int,,,True
449a30a14d55d5eb735468fac84e2dca5bcf75e4,PMC,An evaluation of contaminated complete feed as a vehicle for porcine epidemic diarrhea virus infection of naïve pigs following consumption via natural feeding behavior: proof of concept,http://dx.doi.org/10.1186/s12917-014-0176-9,PMC4363994,25091641,CC BY,"BACKGROUND: Since its initial detection in May 2013, porcine epidemic diarrhea virus (PEDV) has spread rapidly throughout the US swine industry. Initially, contaminated feed was proposed as a risk factor for PEDV; however, data were not available to support this theory. Here we provide proof of concept of this risk by describing a novel means for recovering PEDV-contaminated complete feed material from commercial swine sites and conducting an in vivo experiment to prove its infectivity. RESULTS: For on-farm detection of PEDV RNA in feed, paint rollers were used to collect material from at-risk feed bins from 3 clinically affected breeding herds. This material was tested by PCR and determined to be positive for PEDV-RNA (Ct = 19.50-22.20 range). To test infectivity, this material was pooled (Ct = 20.65) and a Treatment group of 3-week old PEDV-naïve piglets were allowed to consume it via natural feeding behavior. For the purpose of a Positive control, piglets were allowed to ingest feed spiked with stock PEDV (Ct = 18.23) while the negative control group received PEDV-free feed. Clinical signs of PEDV infection (vomiting and diarrhea) and viral shedding were observed in both the Positive control and Treatment group’ post-consumption with virus and microscopic lesions detected in intestinal samples No evidence of infection was observed in the Negative controls. CONCLUSIONS: These data provide proof of concept that contaminated complete feed can serve as a vehicle for PEDV infection of naïve pigs using natural feeding behavior.",2014 Aug 5,"['Dee, Scott', 'Clement, Travis', 'Schelkopf, Adam', 'Nerem, Joel', 'Knudsen, David', 'Christopher-Hennings, Jane', 'Nelson, Eric']",BMC Vet Res,,,True
38f94d6ff230d6a00680940606d559f893701898,PMC,Monoclonal antibody specific to HA2 glycopeptide protects mice from H3N2 influenza virus infection,http://dx.doi.org/10.1186/s13567-015-0146-7,PMC4364502,25888728,CC BY,"Canine influenza virus (CIV) subtype H3N2 is a newly identified, highly contagious respiratory pathogen that causes cough, pneumonia and other respiratory symptoms in dogs. Data indicate that the virus is responsible for recent clinical cases of dog disease in China. However, therapeutic options for this disease are very limited. In this study, seven monoclonal antibodies (mAbs) against CIV JS/10 (an H3N2 subtype virus) were produced and characterized. Among them, mAb D7, which is specific for the HA2 glycopeptide (gp), induced the highest neutralization titers. The protection provided by mAb D7 was evaluated in BALB/c mice challenged with homologous or heterologous strains of H3N2 influenza virus, including two strains of CIV and one strain of swine influenza virus (SIV). The data show that mAb D7 protected the mice from infection with the three viral strains, especially the homologous strain, which was indicated by the recovery of body weight, reduction of viral load, and reduction of tissue damage. Moreover, the levels of IFN-γ and TNF-α in the lungs, as detected by ELISA, were reduced in the infected mice treated with the mAb D7 compared with those without mAb D7 treatment. Thus, our findings demonstrate, for the first time, that a mAb could reduce the release of IFN-γ and TNF-α associated with tissue damage by CIV infection and that the mAb might be of great therapeutic value for CIV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-015-0146-7) contains supplementary material, which is available to authorized users.",2015 Mar 19,"['Xie, Xing', 'Lin, Yan', 'Pang, Maoda', 'Zhao, Yanbing', 'Kalhoro, Dildar Hussain', 'Lu, Chengping', 'Liu, Yongjie']",Vet Res,,,True
c16c86f79a95eff0e99629650c962b25249281af,PMC,Comparative analysis of cytokine transcript profiles within mediastinal lymph node compartments of pigs after infection with porcine reproductive and respiratory syndrome genotype 1 strains differing in pathogenicity,http://dx.doi.org/10.1186/s13567-015-0161-8,PMC4364558,25889072,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) induces a weak immune response enabling it to persist in different organs of infected pigs. This has been attributed to the ability of PRRSV to influence the induction of cytokine responses. In this study, we investigated the cytokine transcriptional profiles in different compartments of the mediastinal lymph node of pigs infected with three genotype 1 PRRSV strains of differing pathogenicity: the low virulence prototype Lelystad virus (LV), and UK field strain 215–06 and the highly virulent subtype 3 SU1-Bel isolate from Belarus. We have used a combination of laser capture micro-dissection (LCM) followed by real time quantitative PCR (RT-qPCR) and immunohistochemical (IHC) detection of immune cell markers (CD3, CD79a and MAC387) and RT-qPCR quantification of PRRSV and cytokine transcripts. Compared to mock infected pigs, we found a significant downregulation of TNF-α and IFN-α in follicular and interfollicular areas of the mediastinal lymph node from 3 days post-infection (dpi) in animals infected with all three strains. This was accompanied by a transient B cell depletion and T cell and macrophage infiltration in the follicles together with T cell depletion in the interfollicular areas. A delayed upregulation of IFN-γ and IL-23p19 was observed mainly in the follicles. The PRRSV load was higher in all areas and time-points studied in the animals infected with the SU1-Bel strain. This paper describes the first application of LCM to study the cytokine transcript profiles and virus distribution in different compartments of the lymph node of pigs.",2015 Mar 19,"['García-Nicolás, Obdulio', 'Rosales, Rubén S', 'Pallarés, Francisco J', 'Risco, David', 'Quereda, Juan J', 'Graham, Simon P', 'Frossard, Jean-Pierre', 'Morgan, Sophie B', 'Steinbach, Falko', 'Drew, Trevor W', 'Strickland, Tony S', 'Salguero, Francisco J']",Vet Res,,,True
cde537507323b28a413a559c934c435b24546c63,PMC,Isolation and Identification of a Natural Reassortant Mammalian Orthoreovirus from Least Horseshoe Bat in China,http://dx.doi.org/10.1371/journal.pone.0118598,PMC4364601,25781475,CC BY,"BACKGROUND: Mammalian orthoreoviruses (MRVs) have a wide geographic distribution and can infect virtually all mammals. Infections in humans may be either symptomatic or asymptomatic. This study describes the isolation and identification of a natural reassortant MRV from least horseshoe bats (Rhinolophus pusillu) in China, referred to as RpMRV-YN2012. METHODS AND RESULTS: The RpMRV-YN2012 was obtained from urine samples of Rhinolophus pusillus by cell culture. Negative-staining electron microscopy revealed that RpMRV-YN2012 was a non-enveloped icosahedral virus with ∼75 nm in diameter. Polyacrylamide gel electrophoresis (PAGE) migration patterns of the genome segments showed that RpMRV-YN2012 contained 10 segments in a 3:3:4 arrangement. The whole genome sequence of RpMRV2012 was determined. The consensus terminal sequences of all segments of 5’-GCUAh…yUCAUC-3’ (h = A, U or C; y = C or U) were similar to the MRV species within the genus Orthoreovirus. Its evolution and evidence of genetic reassortment were analyzed by sequence comparison and phylogenetic analysis. The results showed that RpMRV-YN2012 is a novel serotype 2 MRV that may have originated from reassortment among bat, human, and/or pig MRV strains which associated with diarrhea, acute gastroenteritis and necrotizing encephalopathy in animals and humans. CONCLUSIONS: RpMRV-YN2012 is a novel bat reassortant MRV, which may have resulted from a reassortment involving MRVs known to infect humans and animals. It is necessary to identify whether RpMRV-YN2012 is associated with diarrhea, acute gastroenteritis and necrotizing encephalopathy in clinical patients. In addition, we should carefully monitor its evolution and virulence in real time.",2015 Mar 17,"['Wang, Lihua', 'Fu, Shihong', 'Cao, Lei', 'Lei, Wenwen', 'Cao, Yuxi', 'Song, Jingdong', 'Tang, Qing', 'Zhang, Hailin', 'Feng, Yun', 'Yang, Weihong', 'Liang, Guodong']",PLoS One,,,True
592c1efd20dcb1ff5644f5d20e76f2c28a2b8da0,PMC,Vaccination with Human Papillomavirus Pseudovirus-Encapsidated Plasmids Targeted to Skin Using Microneedles,http://dx.doi.org/10.1371/journal.pone.0120797,PMC4364728,25785935,CC0,"Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1) whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2) whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV) were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation.",2015 Mar 18,"['Kines, Rhonda C.', 'Zarnitsyn, Vladimir', 'Johnson, Teresa R.', 'Pang, Yuk-Ying S.', 'Corbett, Kizzmekia S.', 'Nicewonger, John D.', 'Gangopadhyay, Anu', 'Chen, Man', 'Liu, Jie', 'Prausnitz, Mark R.', 'Schiller, John T.', 'Graham, Barney S.']",PLoS One,,,True
96ae683c7f824b0810ce750d60c15181b93181a4,PMC,Establishment of Hairy Root Cultures by Agrobacterium Rhizogenes Mediated Transformation of Isatis Tinctoria L. for the Efficient Production of Flavonoids and Evaluation of Antioxidant Activities,http://dx.doi.org/10.1371/journal.pone.0119022,PMC4364778,25785699,CC BY,"In this work, Isatis tinctoria hairy root cultures (ITHRCs) were established as an alternative source for flavonoids (FL) production. I. tinctoria hairy root line V was found to be the most efficient line and was further confirmed by the PCR amplification of rolB, rolC and aux1 genes. Culture parameters of ITHRCs were optimized by Box-Behnken design (BBD), and eight bioactive FL constituents (rutin, neohesperidin, buddleoside, liquiritigenin, quercetin, isorhamnetin, kaempferol and isoliquiritigenin) were quali-quantitatively determined by LC-MS/MS. Under optimal conditions, the total FL accumulation of ITHRCs (24 day-old) achieved was 438.10 μg/g dry weight (DW), which exhibited significant superiority as against that of 2 year-old field grown roots (341.73 μg/g DW). Additionally, in vitro antioxidant assays demonstrated that ITHRCs extracts exhibited better antioxidant activities with lower IC(50) values (0.41 and 0.39, mg/mL) as compared to those of field grown roots (0.56 and 0.48, mg/mL). To the best of our knowledge, this is the first report describing FL production and antioxidant activities from ITHRCs.",2015 Mar 18,"['Gai, Qing-Yan', 'Jiao, Jiao', 'Luo, Meng', 'Wei, Zuo-Fu', 'Zu, Yuan-Gang', 'Ma, Wei', 'Fu, Yu-Jie']",PLoS One,,,True
9a0fe7316ddd2f7cfcaa5e7500f781357477f3d1,PMC,A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections,http://dx.doi.org/10.1371/journal.pone.0120012,PMC4364938,25785720,CC BY,"Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.",2015 Mar 18,"['Oved, Kfir', 'Cohen, Asi', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Kriger, Or', 'Bamberger, Ellen', 'Fonar, Yura', 'Yacobov, Renata', 'Wolchinsky, Ron', 'Denkberg, Galit', 'Dotan, Yaniv', 'Hochberg, Amit', 'Reiter, Yoram', 'Grupper, Moti', 'Srugo, Isaac', 'Feigin, Paul', 'Gorfine, Malka', 'Chistyakov, Irina', 'Dagan, Ron', 'Klein, Adi', 'Potasman, Israel', 'Eden, Eran']",PLoS One,,,True
eb4ec643240ca1dd5d566ff1fcf0a36fa97ee7fb,PMC,A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections,http://dx.doi.org/10.1371/journal.pone.0120012,PMC4364938,25785720,CC BY,"Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.",2015 Mar 18,"['Oved, Kfir', 'Cohen, Asi', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Kriger, Or', 'Bamberger, Ellen', 'Fonar, Yura', 'Yacobov, Renata', 'Wolchinsky, Ron', 'Denkberg, Galit', 'Dotan, Yaniv', 'Hochberg, Amit', 'Reiter, Yoram', 'Grupper, Moti', 'Srugo, Isaac', 'Feigin, Paul', 'Gorfine, Malka', 'Chistyakov, Irina', 'Dagan, Ron', 'Klein, Adi', 'Potasman, Israel', 'Eden, Eran']",PLoS One,,,False
d692faf09c38fc62f237f0ff9f2b3a2751ff76f7,PMC,A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections,http://dx.doi.org/10.1371/journal.pone.0120012,PMC4364938,25785720,CC BY,"Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.",2015 Mar 18,"['Oved, Kfir', 'Cohen, Asi', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Kriger, Or', 'Bamberger, Ellen', 'Fonar, Yura', 'Yacobov, Renata', 'Wolchinsky, Ron', 'Denkberg, Galit', 'Dotan, Yaniv', 'Hochberg, Amit', 'Reiter, Yoram', 'Grupper, Moti', 'Srugo, Isaac', 'Feigin, Paul', 'Gorfine, Malka', 'Chistyakov, Irina', 'Dagan, Ron', 'Klein, Adi', 'Potasman, Israel', 'Eden, Eran']",PLoS One,,,True
9148852f390403699eb166e03dc4147520b7ed5e,PMC,A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections,http://dx.doi.org/10.1371/journal.pone.0120012,PMC4364938,25785720,CC BY,"Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.",2015 Mar 18,"['Oved, Kfir', 'Cohen, Asi', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Kriger, Or', 'Bamberger, Ellen', 'Fonar, Yura', 'Yacobov, Renata', 'Wolchinsky, Ron', 'Denkberg, Galit', 'Dotan, Yaniv', 'Hochberg, Amit', 'Reiter, Yoram', 'Grupper, Moti', 'Srugo, Isaac', 'Feigin, Paul', 'Gorfine, Malka', 'Chistyakov, Irina', 'Dagan, Ron', 'Klein, Adi', 'Potasman, Israel', 'Eden, Eran']",PLoS One,,,True
0f9aaacbdad195c0133c25eb6dc02585ba7e1e2b,PMC,A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections,http://dx.doi.org/10.1371/journal.pone.0120012,PMC4364938,25785720,CC BY,"Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.",2015 Mar 18,"['Oved, Kfir', 'Cohen, Asi', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Kriger, Or', 'Bamberger, Ellen', 'Fonar, Yura', 'Yacobov, Renata', 'Wolchinsky, Ron', 'Denkberg, Galit', 'Dotan, Yaniv', 'Hochberg, Amit', 'Reiter, Yoram', 'Grupper, Moti', 'Srugo, Isaac', 'Feigin, Paul', 'Gorfine, Malka', 'Chistyakov, Irina', 'Dagan, Ron', 'Klein, Adi', 'Potasman, Israel', 'Eden, Eran']",PLoS One,,,True
50c5334ead9ce88189c0840243fb64fa9599bfdb,PMC,A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections,http://dx.doi.org/10.1371/journal.pone.0120012,PMC4364938,25785720,CC BY,"Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.",2015 Mar 18,"['Oved, Kfir', 'Cohen, Asi', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Kriger, Or', 'Bamberger, Ellen', 'Fonar, Yura', 'Yacobov, Renata', 'Wolchinsky, Ron', 'Denkberg, Galit', 'Dotan, Yaniv', 'Hochberg, Amit', 'Reiter, Yoram', 'Grupper, Moti', 'Srugo, Isaac', 'Feigin, Paul', 'Gorfine, Malka', 'Chistyakov, Irina', 'Dagan, Ron', 'Klein, Adi', 'Potasman, Israel', 'Eden, Eran']",PLoS One,,,True
dd5f8cf7e557b09094248fd8fbc59fbf7f01649e,PMC,A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections,http://dx.doi.org/10.1371/journal.pone.0120012,PMC4364938,25785720,CC BY,"Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse.",2015 Mar 18,"['Oved, Kfir', 'Cohen, Asi', 'Boico, Olga', 'Navon, Roy', 'Friedman, Tom', 'Etshtein, Liat', 'Kriger, Or', 'Bamberger, Ellen', 'Fonar, Yura', 'Yacobov, Renata', 'Wolchinsky, Ron', 'Denkberg, Galit', 'Dotan, Yaniv', 'Hochberg, Amit', 'Reiter, Yoram', 'Grupper, Moti', 'Srugo, Isaac', 'Feigin, Paul', 'Gorfine, Malka', 'Chistyakov, Irina', 'Dagan, Ron', 'Klein, Adi', 'Potasman, Israel', 'Eden, Eran']",PLoS One,,,True
45c54d1883027b09c51ea00cb13b1980569592a6,PMC,Viral aetiology of acute respiratory infections among children and associated meteorological factors in southern China,http://dx.doi.org/10.1186/s12879-015-0863-6,PMC4365542,25884513,CC BY,"BACKGROUND: Acute respiratory infections (ARIs) are common in children and mostly caused by viruses, but the significance of the detection of multiple viruses in ARIs is unclear. This study investigated 14 respiratory viruses in ARIs among children and associated meteorological factors in Shantou, southern China. METHODS: Paired nasal/throat-flocked swabs collected from 1,074 children with ARIs, who visited outpatient walk-in clinics in a tertiary hospital between December 2010 and November 2011, were examined for fourteen respiratory viruses - influenza viruses (FluA, FluB), respiratory syncytial viruses (RSV A and B), human coronaviruses (hCoV: 229E, OC43, HKU1, NL63), human metapneumoviruses (hMPV A and B), parainfluenza viruses (PIV1-4), human rhinoviruses (HRV A, B, C), enteroviruses (EV), adenoviruses (ADV), human bocavirus (hBoV), and human parechoviruses (hPeV) - by multiplex real-time PCR. RESULTS: We identified at least one virus in 82.3% (884/1,074) and multiple viruses in 38.6% (415/1,074) of patients. EV and HRV were the most frequently detected single viruses (42.3%, 374/884 and 39.9%, 353/884 respectively) and co-detected pair (23.1%, 96/415). Overlapping seasonal trends of viruses were recorded over the year, with dual peaks for EV and single peaks for the others. By logistic regression analysis, EV was positively associated with the average temperature and humidity, hCoV, and PIV4, but negatively with HRV, PIV3, and hBoV. HRV was inversely associated with EV and PIV3. CONCLUSIONS: This study reports high viral detection and co-detection rates in pediatric ARI cases mainly due to EV and HRV. Many viruses circulated throughout the year with similar seasonal trends in association with temperature, humidity, and wind velocity. Statistically significant associations were present among the viruses. Understanding the polyviral etiology and viral interactions in the cases with multiple viruses warrants further studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0863-6) contains supplementary material, which is available to authorized users.",2015 Mar 13,"['Cui, Binglin', 'Zhang, Dangui', 'Pan, Hui', 'Zhang, Fan', 'Farrar, Jeremy', 'Law, Frieda', 'van Doorn, H Rogier', 'Wu, Beiyan', 'Ba-Thein, William']",BMC Infect Dis,,,True
c98b61b984da63b53eeef9f81e31a5ee79396b1d,PMC,Bovine Rhinitis Viruses Are Common in U.S. Cattle with Bovine Respiratory Disease,http://dx.doi.org/10.1371/journal.pone.0121998,PMC4366061,25789939,CC BY,"Bovine rhinitis viruses (BRV) are established etiological agents of bovine respiratory disease complex however little research into their epidemiology and ecology has been published for several decades. In the U.S., only bovine rhinitis A virus 1 (BRAV1) has been identified while bovine rhinitis A virus 2 (BRAV2) and bovine rhinitis B virus (BRBV) were previously only identified in England and Japan, respectively. Metagenomic sequencing of a nasal swab from a bovine respiratory disease (BRD) diagnostic submission from Kansas identified contigs with approximately 90% nucleotide similarity to BRAV2 and BRBV. A combination of de novo and templated assemblies using reference genomes yielded near complete BRAV2 and BRBV genomes. The near complete genome of bovine rhinitis A virus 1 (BRAV1) was also determined from a historical isolate to enable further molecular epidemiological studies. A 5’-nuclease reverse transcription PCR assay targeting the 3D polymerase gene was designed and used to screen 204 archived BRD clinical specimens. Thirteen (6.4%) were positive. Metagenomic sequencing of six positive samples identified mixed BRAV1/BRAV2, BRAV1/BRBV and BRAV2/BRBV infections for five samples. One sample showed infection only with BRAV1. Seroprevalence studies using a cell culture adapted BRBV found immunofluorescence assay-reactive antibodies were common in the herds analyzed. Altogether, these results demonstrate that BRV infections are common in cattle with respiratory disease and that BRAV1, BRAV2 and BRBV co-circulate in U.S. cattle and have high similarity to viruses isolated more than 30 years ago from diverse locations.",2015 Mar 19,"['Hause, Ben M.', 'Collin, Emily A.', 'Anderson, Joe', 'Hesse, Richard A.', 'Anderson, Gary']",PLoS One,,,True
7d2bd0d04e9e4418d308e40557a3c397eaada71d,PMC,"Molecular Characterization and Phylogenetic Analysis of Porcine Epidemic Diarrhea Viruses Associated with Outbreaks of Severe Diarrhea in Piglets in Jiangxi, China 2013",http://dx.doi.org/10.1371/journal.pone.0120310,PMC4366183,25790462,CC BY,"Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV), is a highly contagious, acute enteric viral disease of swine characterized by vomiting, watery diarrhea, dehydration and death. To identify and characterize the field PEDVs associated with the outbreaks of severe diarrhea in piglets in Jiangxi, 2013, the complete genome sequences of two representative strains of PEDV, designated CH/JX-1/2013 and CH/JX-2/2013, were determined and analyzed. The genome sequences of both emergent Jiangxi PEDV strains, CH/JX-1/2013 and CH/JX-2/2013, were 28,038 nucleotides in length excluding 3’ poly (A) tail. Compared to the PEDV CV777 strain, CH/JX-1/2013 and CH/JX-2/2013 had some unique genetic characteristics in the proximal region of the 5´-UTRs. Phylogenetic analysis of the complete genomes and the structural proteins revealed that CH/JX-1/2013 and CH/JX-2/2013 had a close relationship with post-2010 Chinese PEDV strains and US strains identified in 2013. The nucleotide identity between the two Jiangxi strains (CH/JX-1/2013 and CH/JX-2/2013) and 30 strains of PEDV identified ante-2010 and post-2010 ranged from 96.3–97.0% and 97.3–99.7%, respectively. Multiple nucleotide and deduced amino acid mutations were observed in the ORF1a/b, S, ORF3, E, M and N genes among the current field PEDV strains when compared to the CV777 strain. Some of the mutations altered the amino acid charge and hydrophilicity, and notably, there was an amino acid substitution in the middle of one neutralizing epitope (L1371I) of the S gene of both CH/JX-1/2013 and CH/JX-2/2013. Taken together, the accumulated genetic variations of the current field PEDV strains might have led to antigenic changes of the viruses, which might confer the less effectiveness or failure of the CV777-based vaccines currently being widely used in Jiangxi, China.",2015 Mar 19,"['Song, Deping', 'Huang, Dongyan', 'Peng, Qi', 'Huang, Tao', 'Chen, Yanjun', 'Zhang, Tiansheng', 'Nie, Xiaowei', 'He, Houjun', 'Wang, Ping', 'Liu, Qinglan', 'Tang, Yuxin']",PLoS One,,,True
4d44402d0831ef5a86694ff70f9764a46fa06deb,PMC,Sublingual Immunization of Trivalent Human Papillomavirus DNA Vaccine in Baculovirus Nanovector for Protection against Vaginal Challenge,http://dx.doi.org/10.1371/journal.pone.0119408,PMC4366369,25789464,CC BY,"Here, we report the immunogenicity of a sublingually delivered, trivalent human papillomavirus (HPV) DNA vaccine encapsidated in a human endogenous retrovirus (HERV) envelope-coated, nonreplicable, baculovirus nanovector. The HERV envelope-coated, nonreplicable, baculovirus-based DNA vaccine, encoding HPV16L1, -18L1 and -58L1 (AcHERV-triHPV), was constructed and sublingually administered to mice without adjuvant. Following sublingual (SL) administration, AcHERV-triHPV was absorbed and distributed throughout the body. At 15 minutes and 1 day post-dose, the distribution of AcHERV-triHPV to the lung was higher than that to other tissues. At 30 days post-dose, the levels of AcHERV-triHPV had diminished throughout the body. Six weeks after the first of three doses, 1×10(8) copies of SL AcHERV-triHPV induced HPV type-specific serum IgG and neutralizing antibodies to a degree comparable to that of IM immunization with 1×10(9) copies. AcHERV-triHPV induced HPV type-specific vaginal IgA titers in a dose-dependent manner. SL immunization with 1×10(10) copies of AcHERV-triHPV induced Th1 and Th2 cellular responses comparable to IM immunization with 1×10(9) copies. Molecular imaging revealed that SL AcHERV-triHPV in mice provided complete protection against vaginal challenge with HPV16, HPV18, and HPV58 pseudoviruses. These results support the potential of SL immunization using multivalent DNA vaccine in baculovirus nanovector for induction of mucosal, systemic, and cellular immune responses.",2015 Mar 19,"['Lee, Hee-Jung', 'Cho, Hansam', 'Kim, Mi-Gyeong', 'Heo, Yoon-Ki', 'Cho, Yeondong', 'Gwon, Yong-Dae', 'Park, Ki Hoon', 'Jin, Hyerim', 'Kim, Jinyoung', 'Oh, Yu-Kyoung', 'Kim, Young Bong']",PLoS One,,,True
f3025ff285a3ab111229e38adaa5edb38406d3e1,PMC,The Impact of Prior Information on Estimates of Disease Transmissibility Using Bayesian Tools,http://dx.doi.org/10.1371/journal.pone.0118762,PMC4368801,25793993,CC BY,"The basic reproductive number (R₀) and the distribution of the serial interval (SI) are often used to quantify transmission during an infectious disease outbreak. In this paper, we present estimates of R₀ and SI from the 2003 SARS outbreak in Hong Kong and Singapore, and the 2009 pandemic influenza A(H1N1) outbreak in South Africa using methods that expand upon an existing Bayesian framework. This expanded framework allows for the incorporation of additional information, such as contact tracing or household data, through prior distributions. The results for the R₀ and the SI from the influenza outbreak in South Africa were similar regardless of the prior information ([Image: see text] = 1.36–1.46, [Image: see text] = 2.0–2.7, [Image: see text] = mean of the SI). The estimates of R₀ and μ for the SARS outbreak ranged from 2.0–4.4 and 7.4–11.3, respectively, and were shown to vary depending on the use of contact tracing data. The impact of the contact tracing data was likely due to the small number of SARS cases relative to the size of the contact tracing sample.",2015 Mar 20,"['Moser, Carlee B.', 'Gupta, Mayetri', 'Archer, Brett N.', 'White, Laura F.']",PLoS One,,,True
e64a2ab805fe19fae40eb382eccb7ea82a997a1d,PMC,Proteomic Analysis of Urine Exosomes Reveals Renal Tubule Response to Leptospiral Colonization in Experimentally Infected Rats,http://dx.doi.org/10.1371/journal.pntd.0003640,PMC4368819,25793258,CC BY,"BACKGROUND: Infectious Leptospira colonize the kidneys of reservoir (e.g. rats) and accidental hosts such as humans. The renal response to persistent leptospiral colonization, as measured by urinary protein biosignatures, has not been systematically studied. Urinary exosomes--bioactive membrane-bound nanovesicles--contain cell-state specific cargo that additively reflect formation all along the nephron. We hypothesized that Leptospira-infection will alter the content of urine exosomes, and further, that these Leptospira-induced alterations will hold clues to unravel novel pathways related to bacterial-host interactions. METHODOLOGY/PRINCIPAL FINDINGS: Exosome protein content from 24 hour urine samples of Leptospira-infected rats was compared with that of uninfected rats using SDS-PAGE and liquid chromatography/tandem mass spectrometry (LC-MS/MS). Statistical models were used to identify significantly dysregulated proteins in Leptospira-infected and uninfected rat urine exosomes. In all, 842 proteins were identified by LC-MS/MS proteomics of total rat urine and 204 proteins associated specifically with exosomes. Multivariate analysis showed that 25 proteins significantly discriminated between uninfected control and infected rats. Alanyl (membrane) aminopeptidase, also known as CD13 topped this list with the highest score, a finding we validated by Western immunoblotting. Whole urine analysis showed Tamm-Horsfall protein level reduction in the infected rat urine. Total urine and exosome proteins were significantly different in male vs. female infected rats. CONCLUSIONS: We identified exosome-associated renal tubule-specific responses to Leptospira infection in a rat chronic colonization model. Quantitative differences in infected male and female rat urine exosome proteins vs. uninfected controls suggest that urine exosome analysis identifies important differences in kidney function that may be of clinical and pathological significance.",2015 Mar 20,"['RamachandraRao, Satish P.', 'Matthias, Michael A.', 'Mondrogon, Chanthel-Kokoy', 'Aghania, Eamon', 'Park, Cathleen', 'Kong, Casey', 'Ishaya, Michelle', 'Madrigal, Assael', 'Horng, Jennifer', 'Khoshaba, Roni', 'Bounkhoun, Anousone', 'Basilico, Fabrizio', 'De Palma, Antonella', 'Agresta, Anna Maria', 'Awdishu, Linda', 'Naviaux, Robert K.', 'Vinetz, Joseph M.', 'Mauri, Pierluigi']",PLoS Negl Trop Dis,,,True
51b8bdc5f732c68e830a09eb2ecd73191e6df2dd,PMC,Bats and zoonotic viruses: can we confidently link bats with emerging deadly viruses?,http://dx.doi.org/10.1590/0074-02760150048,PMC4371215,25742261,CC BY,"An increasingly asked question is 'can we confidently link bats with emerging viruses?'. No, or not yet, is the qualified answer based on the evidence available. Although more than 200 viruses - some of them deadly zoonotic viruses - have been isolated from or otherwise detected in bats, the supposed connections between bats, bat viruses and human diseases have been raised more on speculation than on evidence supporting their direct or indirect roles in the epidemiology of diseases (except for rabies). However, we are convinced that the evidence points in that direction and that at some point it will be proved that bats are competent hosts for at least a few zoonotic viruses. In this review, we cover aspects of bat biology, ecology and evolution that might be relevant in medical investigations and we provide a historical synthesis of some disease outbreaks causally linked to bats. We provide evolutionary-based hypotheses to tentatively explain the viral transmission route through mammalian intermediate hosts and to explain the geographic concentration of most outbreaks, but both are no more than speculations that still require formal assessment.",2015 Feb,"['Moratelli, Ricardo', 'Calisher, Charles H']",Mem Inst Oswaldo Cruz,,,True
34b2b1fe3361c684f52c9a60f48f579edb8f52dc,PMC,"Effect of Puumala hantavirus infection on human umbilical vein endothelial cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release",http://dx.doi.org/10.3389/fmicb.2015.00220,PMC4371750,25852676,CC BY,"Puumala virus (PUUV) infection causes over 5000 cases of hemorrhagic fever in Europe annually and can influence the hemostatic balance extensively. Infection might lead to hemorrhage, while a recent study showed an increased risk of myocardial infarction during or shortly after PUUV infection. The mechanism by which this hantavirus influences the coagulation system remains unknown. Therefore we aimed to elucidate mechanisms explaining alterations seen in primary and secondary hemostasis during PUUV infection. By using low passage PUUV isolates to infect primary human umbilical vein endothelial cells (HUVECs) we were able to show alterations in the regulation of primary- and secondary hemostasis and in the release of fibrinolysis regulators. Our main finding was an activation of secondary hemostasis due to increased tissue factor (TF) expression leading to increased thrombin generation in a functional assay. Furthermore, we showed that during infection platelets adhered to HUVEC and subsequently specifically to PUUV virus particles. Infection of HUVEC with PUUV did not result in increased von Willebrand factor while they produced more plasminogen activator inhibitor type-1 (PAI-1) compared to controls. The PAI-1 produced in this model formed complexes with vitronectin. This is the first report that reveals a potential mechanism behind the pro-coagulant changes in PUUV patients, which could be the result of increased thrombin generation due to an increased TF expression on endothelial cells during infection. Furthermore, we provide insight into the contribution of endothelial cell responses regarding hemostasis in PUUV pathogenesis.",2015 Mar 24,"['Goeijenbier, Marco', 'Meijers, Joost C. M.', 'Anfasa, Fatih', 'Roose, Jeroen M.', 'van de Weg, Cornelia A. M.', 'Bakhtiari, Kamran', 'Henttonen, Heikki', 'Vaheri, Antti', 'Osterhaus, Albert D. M. E.', 'van Gorp, Eric C. M.', 'Martina, Byron E. E.']",Front Microbiol,,,True
715ec0aac4ad78092007345159945afa560b3f05,PMC,Strengthening the Detection of and Early Response to Public Health Emergencies: Lessons from the West African Ebola Epidemic,http://dx.doi.org/10.1371/journal.pmed.1001804,PMC4371887,25803303,CC BY,Mark Siedner and colleagues reflect on the early response to the Ebola epidemic and lessons that can be learned for future epidemics.,2015 Mar 24,"['Siedner, Mark J.', 'Gostin, Lawrence O.', 'Cranmer, Hilarie H.', 'Kraemer, John D.']",PLoS Med,,,True
fff3678cfe3ce7a9ccae1e7becf17d5d71d1b54a,PMC,Gaining Insights into the Codon Usage Patterns of TP53 Gene across Eight Mammalian Species,http://dx.doi.org/10.1371/journal.pone.0121709,PMC4373688,25807269,CC BY,"TP53 gene is known as the “guardian of the genome” as it plays a vital role in regulating cell cycle, cell proliferation, DNA damage repair, initiation of programmed cell death and suppressing tumor growth. Non uniform usage of synonymous codons for a specific amino acid during translation of protein known as codon usage bias (CUB) is a unique property of the genome and shows species specific deviation. Analysis of codon usage bias with compositional dynamics of coding sequences has contributed to the better understanding of the molecular mechanism and the evolution of a particular gene. In this study, the complete nucleotide coding sequences of TP53 gene from eight different mammalian species were used for CUB analysis. Our results showed that the codon usage patterns in TP53 gene across different mammalian species has been influenced by GC bias particularly GC(3) and a moderate bias exists in the codon usage of TP53 gene. Moreover, we observed that nature has highly favored the most over represented codon CTG for leucine amino acid but selected against the ATA codon for isoleucine in TP53 gene across all mammalian species during the course of evolution.",2015 Mar 25,"['Mazumder, Tarikul Huda', 'Chakraborty, Supriyo']",PLoS One,,,True
b70653608d4d8838aaf1dae4e710fa03a858df43,PMC,The Highly Conserved Codon following the Slippery Sequence Supports −1 Frameshift Efficiency at the HIV-1 Frameshift Site,http://dx.doi.org/10.1371/journal.pone.0122176,PMC4373837,25807539,CC BY,"HIV-1 utilises −1 programmed ribosomal frameshifting to translate structural and enzymatic domains in a defined proportion required for replication. A slippery sequence, U UUU UUA, and a stem-loop are well-defined RNA features modulating −1 frameshifting in HIV-1. The GGG glycine codon immediately following the slippery sequence (the ‘intercodon’) contributes structurally to the start of the stem-loop but has no defined role in current models of the frameshift mechanism, as slippage is inferred to occur before the intercodon has reached the ribosomal decoding site. This GGG codon is highly conserved in natural isolates of HIV. When the natural intercodon was replaced with a stop codon two different decoding molecules—eRF1 protein or a cognate suppressor tRNA—were able to access and decode the intercodon prior to −1 frameshifting. This implies significant slippage occurs when the intercodon is in the (perhaps distorted) ribosomal A site. We accommodate the influence of the intercodon in a model of frame maintenance versus frameshifting in HIV-1.",2015 Mar 25,"['Mathew, Suneeth F.', 'Crowe-McAuliffe, Caillan', 'Graves, Ryan', 'Cardno, Tony S.', 'McKinney, Cushla', 'Poole, Elizabeth S.', 'Tate, Warren P.']",PLoS One,,,True
9413ac12d29207f16ff2983940960e00f296ec15,PMC,Virocidal activity of Egyptian scorpion venoms against hepatitis C virus,http://dx.doi.org/10.1186/s12985-015-0276-6,PMC4374190,25889296,CC BY,"BACKGROUND: Hepatitis C virus (HCV) is a major global health problem, causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Development of well-tolerated regimens with high cure rates and fewer side effects is still much needed. Recently, natural antimicrobial peptides (AMPs) are attracting more attention as biological compounds and can be a good template to develop therapeutic agents, including antiviral agents against a variety of viruses. Various AMPs have been characterized from the venom of different venomous animals including scorpions. METHODS: The possible antiviral activities of crude venoms obtained from five Egyptian scorpion species (Leiurus quinquestriatus, Androctonus amoreuxi, A. australis, A. bicolor and Scorpio maurus palmatus) were evaluated by a cell culture method using Huh7.5 cells and the J6/JFH1-P47 strain of HCV. Time-of-addition experiments and inactivation of enzymatic activities of the venoms were carried out to determine the characteristics of the anti-HCV activities. RESULTS: S. maurus palmatus and A. australis venoms showed anti-HCV activities, with 50% inhibitory concentrations (IC(50)) being 6.3 ± 1.6 and 88.3 ± 5.8 μg/ml, respectively. S. maurus palmatus venom (30 μg/ml) impaired HCV infectivity in culture medium, but not inside the cells, through virocidal effect. The anti-HCV activity of this venom was not inhibited by a metalloprotease inhibitor or heating at 60°C. The antiviral activity was directed preferentially against HCV. CONCLUSIONS: S. maurus palmatus venom is considered as a good natural source for characterization and development of novel anti-HCV agents targeting the entry step. To our knowledge, this is the first report describing antiviral activities of Egyptian scorpion venoms against HCV, and may open a new approach towards discovering antiviral compounds derived from scorpion venoms.",2015 Mar 24,"['El-Bitar, Alaa MH', 'Sarhan, Moustafa MH', 'Aoki, Chie', 'Takahara, Yusuke', 'Komoto, Mari', 'Deng, Lin', 'Moustafa, Mohsen A', 'Hotta, Hak']",Virol J,,,True
b443b0e9659665ac9bba473fb6ade9d2efdeffe6,PMC,Local cross-border disease surveillance and control: experiences from the Mekong Basin,http://dx.doi.org/10.1186/s13104-015-1047-6,PMC4374506,25889232,CC BY,"BACKGROUND: The Mekong Basin Disease Surveillance cooperation (MBDS) is one of several sub-regional disease surveillance networks that have emerged in recent years as an approach to transnational cooperation for infectious disease prevention and control. Since 2003 MBDS has pioneered a unique model for local cross-border cooperation. This study examines stakeholders’ perspectives of these MBDS experiences, based on a survey of local managers and semi-structured interviews with MBDS leaders and the central coordinator. RESULTS: Fifteen managers from 12 of 20 paired cross-border sites completed a written survey. They all monitor most or all of the 17 diseases agreed upon for MBDS surveillance information sharing. Fourteen agreed or strongly agreed with statements about the core MBDS values of cooperation, mutual trust, and transparency, and their own contributions to national and regional disease control (average score of 4.4 of 5.0). Respondents felt they implemented well to very well activities related to surveillance reporting (average scores 3.4 to 3.9 of 4.0), using computers for their work (3.9/4.0), and using surveillance data for action (3.8/4.0). Respondents reported that they did worst in implementing research (2.1/4.0) and somewhat poorly for local laboratory testing (2.9/4.0) and local coordination with cross-border counterparts (2.9/4.0), although all 15 maintain a list with contact information for these counterparts and many know their counterparts. Implementation of specified activities within their collective regional action plan was uneven across the cross-border sites. Most respondents reported positive lessons learned about local cooperation, information sharing and joint problem solving, based on trusting relationships with their cross-border counterparts. They recommend expansion of cross-border sites within MBDS and consideration of the cross-border cooperation model by other sub-regional networks. CONCLUSIONS: MBDS has over a decade of experience with its model of local cross-border cooperation in disease surveillance and control. Frontline managers have documented success with this model, strongly support it and recommend its expansion within and beyond the MBDS network. The MBDS cross-border cooperation model is standing the test of time as a solid approach to building and sustaining the public health capabilities needed for disease surveillance and control from the local to national and global levels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13104-015-1047-6) contains supplementary material, which is available to authorized users.",2015 Mar 21,"['Moore, Melinda', 'Dausey, David J']",BMC Res Notes,,,False
24d93589f9edba05a3f0a95b350bc91cb551814a,PMC,Local cross-border disease surveillance and control: experiences from the Mekong Basin,http://dx.doi.org/10.1186/s13104-015-1047-6,PMC4374506,25889232,CC BY,"BACKGROUND: The Mekong Basin Disease Surveillance cooperation (MBDS) is one of several sub-regional disease surveillance networks that have emerged in recent years as an approach to transnational cooperation for infectious disease prevention and control. Since 2003 MBDS has pioneered a unique model for local cross-border cooperation. This study examines stakeholders’ perspectives of these MBDS experiences, based on a survey of local managers and semi-structured interviews with MBDS leaders and the central coordinator. RESULTS: Fifteen managers from 12 of 20 paired cross-border sites completed a written survey. They all monitor most or all of the 17 diseases agreed upon for MBDS surveillance information sharing. Fourteen agreed or strongly agreed with statements about the core MBDS values of cooperation, mutual trust, and transparency, and their own contributions to national and regional disease control (average score of 4.4 of 5.0). Respondents felt they implemented well to very well activities related to surveillance reporting (average scores 3.4 to 3.9 of 4.0), using computers for their work (3.9/4.0), and using surveillance data for action (3.8/4.0). Respondents reported that they did worst in implementing research (2.1/4.0) and somewhat poorly for local laboratory testing (2.9/4.0) and local coordination with cross-border counterparts (2.9/4.0), although all 15 maintain a list with contact information for these counterparts and many know their counterparts. Implementation of specified activities within their collective regional action plan was uneven across the cross-border sites. Most respondents reported positive lessons learned about local cooperation, information sharing and joint problem solving, based on trusting relationships with their cross-border counterparts. They recommend expansion of cross-border sites within MBDS and consideration of the cross-border cooperation model by other sub-regional networks. CONCLUSIONS: MBDS has over a decade of experience with its model of local cross-border cooperation in disease surveillance and control. Frontline managers have documented success with this model, strongly support it and recommend its expansion within and beyond the MBDS network. The MBDS cross-border cooperation model is standing the test of time as a solid approach to building and sustaining the public health capabilities needed for disease surveillance and control from the local to national and global levels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13104-015-1047-6) contains supplementary material, which is available to authorized users.",2015 Mar 21,"['Moore, Melinda', 'Dausey, David J']",BMC Res Notes,,,True
e39549d1d4e49cf191e2c743e6b82b738e3b21f2,PMC,Complex Epidemiology of a Zoonotic Disease in a Culturally Diverse Region: Phylogeography of Rabies Virus in the Middle East,http://dx.doi.org/10.1371/journal.pntd.0003569,PMC4374968,25811659,CC BY,"The Middle East is a culturally and politically diverse region at the gateway between Europe, Africa and Asia. Spatial dynamics of the fatal zoonotic disease rabies among countries of the Middle East and surrounding regions is poorly understood. An improved understanding of virus distribution is necessary to direct control methods. Previous studies have suggested regular trans-boundary movement, but have been unable to infer direction. Here we address these issues, by investigating the evolution of 183 rabies virus isolates collected from over 20 countries between 1972 and 2014. We have undertaken a discrete phylogeographic analysis on a subset of 139 samples to infer where and when movements of rabies have occurred. We provide evidence for four genetically distinct clades with separate origins currently circulating in the Middle East and surrounding countries. Introductions of these viruses have been followed by regular and multidirectional trans-boundary movements in some parts of the region, but relative isolation in others. There is evidence for minimal regular incursion of rabies from Central and Eastern Asia. These data support current initiatives for regional collaboration that are essential for rabies elimination.",2015 Mar 26,"['Horton, Daniel L.', 'McElhinney, Lorraine M.', 'Freuling, Conrad M.', 'Marston, Denise A.', 'Banyard, Ashley C.', 'Goharrriz, Hooman', 'Wise, Emma', 'Breed, Andrew C.', 'Saturday, Greg', 'Kolodziejek, Jolanta', 'Zilahi, Erika', 'Al-Kobaisi, Muhannad F.', 'Nowotny, Norbert', 'Mueller, Thomas', 'Fooks, Anthony R.']",PLoS Negl Trop Dis,,,True
9ea1a900f1243ce3264700e9eec29b402892674c,PMC,Adenoviruses Associated with Acute Respiratory Diseases Reported in Beijing from 2011 to 2013,http://dx.doi.org/10.1371/journal.pone.0121375,PMC4376766,25816320,CC BY,"BACKGROUND: Adenovirus is one of the most common causes of viral acute respiratory infections. To identify the types of human adenoviruses (HAdVs) causing respiratory illness in Beijing, a sentinel surveillance project on the viral aetiology of acute respiratory infection was initiated in 2011. PRINCIPAL FINDINGS: Through the surveillance project, 4617 cases of respiratory infections were identified during 2011-2013. Throat swabs (pharynx and tonsil secretions) were collected from all the patients, and 15 different respiratory viruses were screened by multiplex one-step PCR method. 45 were identified as adenovirus-positive from sporadic and outbreak cases of respiratory infection by a multiplex one-step RT-PCR method, and a total of 21 adenovirus isolates were obtained. Five HAdV types among three species, including HAdV-3 (species HAdV-B), HAdV-4 (species HAdV-E), HAdV-7 (species HAdV-B), HAdV-55 (species HAdV-B), and an undefined HAdV type (species HAdV-C) were identified. The comparison results of the penton base, hexon, and fiber gene sequences of the Beijing HAdV-3, HAdV-4, HAdV-7, and HAdV-55 strains in this study and those from the GenBank database indicated significant spatial and temporal conservation and stability of sequences within the genome; however, the phylogenetic relationship indicated that both strain BJ04 and strain BJ09 isolated in 2012 and 2013, respectively, may have recombined between HAdV-1 genome and HAdV-2 genome within species HAdV-C, indicating intraspecies recombination. CONCLUSIONS: This study confirmed that at least 5 HAdV types including HAdV-3, HAdV-4, HAdV-7, HAdV-55 and an undefined HAdV type were co-circulating and were the causative agents of respiratory tract infections in recent years in Beijing. HAdV-3, HAdV-4, HAdV-7, and HAdV-55 showed the apparent stability of the genomes, while intraspecies recombination was identified in strain BJ04 and BJ09. The recombinants carrying penton base gene of HAdV-1 as well as hexon and fiber genes of HAdV-2 might be a novel type of HAdV worthy of further study.",2015 Mar 27,"['Chen, Meng', 'Zhu, Zhen', 'Huang, Fang', 'Liu, Donglei', 'Zhang, Tiegang', 'Ying, Deng', 'Wu, Jiang', 'Xu, Wenbo']",PLoS One,,,True
3faebf3f78e4b42abd134372119fde0ed298fa4b,PMC,Cleavage of Dicer Protein by I7 Protease during Vaccinia Virus Infection,http://dx.doi.org/10.1371/journal.pone.0120390,PMC4376780,25815818,CC BY,"Dicer is the key component in the miRNA pathway. Degradation of Dicer protein is facilitated during vaccinia virus (VV) infection. A C-terminal cleaved product of Dicer protein was detected in the presence of MG132 during VV infection. Thus, it is possible that Dicer protein is cleaved by a viral protease followed by proteasome degradation of the cleaved product. There is a potential I7 protease cleavage site in the C-terminus of Dicer protein. Indeed, reduction of Dicer protein was detected when Dicer was co-expressed with I7 protease but not with an I7 protease mutant protein lack of the protease activity. Mutation of the potential I7 cleavage site in the C-terminus of Dicer protein resisted its degradation during VV infection. Furthermore, Dicer protein was reduced dramatically by recombinant VV vI7Li after the induction of I7 protease. If VV could facilitate the degradation of Dicer protein, the process of miRNA should be affected by VV infection. Indeed, accumulation of precursor miR122 was detected after VV infection or I7 protease expression. Reduction of miR122 would result in the suppression of HCV sub-genomic RNA replication, and, in turn, the amount of viral proteins. As expected, significant reduction of HCVNS5A protein was detected after VV infection and I7 protease expression. Therefore, our results suggest that VV could cleave Dicer protein through I7 protease to facilitate Dicer degradation, and in turn, suppress the processing of miRNAs. Effect of Dicer protein on VV replication was also studied. Exogenous expression of Dicer protein suppresses VV replication slightly while knockdown of Dicer protein does not affect VV replication significantly.",2015 Mar 27,"['Chen, Jhih-Si', 'Li, Hui-Chun', 'Lin, Shu-I', 'Yang, Chee-Hing', 'Chien, Wan-Yu', 'Syu, Ciao-Ling', 'Lo, Shih-Yen']",PLoS One,,,True
662d865c6858d8e9f3b7f583719579ee0aeabdfb,PMC,Methicillin-Resistant Staphylococcus aureus (MRSA) Contamination in Bedside Surfaces of a Hospital Ward and the Potential Effectiveness of Enhanced Disinfection with an Antimicrobial Polymer Surfactant,http://dx.doi.org/10.3390/ijerph120303026,PMC4377950,25768241,CC BY,"The aim in this study was to assess the effectiveness of a quaternary ammonium chloride (QAC) surfactant in reducing surface staphylococcal contamination in a routinely operating medical ward occupied by patients who had tested positive for methicillin-resistant Staphylococcus aureus (MRSA). The QAC being tested is an antibacterial film that is sprayed onto a surface and can remain active for up to 8 h. A field experimental study was designed with the QAC plus daily hypochlorite cleaning as the experimental group and hypochlorite cleaning alone as the control group. The method of swabbing on moistened surfaces was used for sampling. It was found that 83% and 77% of the bedside surfaces of MRSA-positive and MRSA-negative patients respectively were contaminated with staphylococci at 08:00 hours, and that the staphylococcal concentrations increased by 80% at 1200 h over a 4-hour period with routine ward and clinical activities. Irrespective of the MRSA status of the patients, high-touch surfaces around the bed-units within the studied medical ward were heavily contaminated (ranged 1 to 276 cfu/cm(2) amongst the sites with positive culture) with staphylococcal bacteria including MRSA, despite the implementation of daily hypochlorite wiping. However, the contamination rate dropped significantly from 78% to 11% after the application of the QAC polymer. In the experimental group, the mean staphylococcal concentration of bedside surfaces was significantly (p < 0.0001) reduced from 4.4 ± 8.7 cfu/cm(2) at 08:00 hours to 0.07 ± 0.26 cfu/cm(2) at 12:00 hours by the QAC polymer. The results of this study support the view that, in addition to hypochlorite wiping, the tested QAC surfactant is a potential environmental decontamination strategy for preventing the transmission of clinically important pathogens in medical wards.",2015 Mar 11,"['Yuen, John W. M.', 'Chung, Terence W. K.', 'Loke, Alice Y.']",Int J Environ Res Public Health,,,True
c67580a2c552483f02b5df1f297d110b4263c5c5,PMC,The Burden and Etiology of Community-Onset Pneumonia in the Aging Japanese Population: A Multicenter Prospective Study,http://dx.doi.org/10.1371/journal.pone.0122247,PMC4378946,25822890,CC BY,"BACKGROUND: The increasing burden of pneumonia in adults is an emerging health issue in the era of global population aging. This study was conducted to elucidate the burden of community-onset pneumonia (COP) and its etiologic fractions in Japan, the world’s most aged society. METHODS: A multicenter prospective surveillance for COP was conducted from September 2011 to January 2013 in Japan. All pneumonia patients aged ≥15 years, including those with community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP), were enrolled at four community hospitals on four major islands. The COP burden was estimated based on the surveillance data and national statistics. RESULTS: A total of 1,772 COP episodes out of 932,080 hospital visits were enrolled during the surveillance. The estimated overall incidence rates of adult COP, hospitalization, and in-hospital death were 16.9 (95% confidence interval, 13.6 to 20.9), 5.3 (4.5 to 6.2), and 0.7 (0.6 to 0.8) per 1,000 person-years (PY), respectively. The incidence rates sharply increased with age; the incidence in people aged ≥85 years was 10-fold higher than that in people aged 15-64 years. The estimated annual number of adult COP cases in the entire Japanese population was 1,880,000, and 69.4% were aged ≥65 years. Aspiration-associated pneumonia (630,000) was the leading etiologic category, followed by Streptococcus pneumoniae-associated pneumonia (530,000), Haemophilus influenzae-associated pneumonia (420,000), and respiratory virus-associated pneumonia (420,000), including influenza-associated pneumonia (30,000). CONCLUSIONS: A substantial portion of the COP burden occurs among elderly members of the Japanese adult population. In addition to the introduction of effective vaccines for S. pneumoniae and influenza, multidimensional approaches are needed to reduce the pneumonia burden in an aging society.",2015 Mar 30,"['Morimoto, Konosuke', 'Suzuki, Motoi', 'Ishifuji, Tomoko', 'Yaegashi, Makito', 'Asoh, Norichika', 'Hamashige, Naohisa', 'Abe, Masahiko', 'Aoshima, Masahiro', 'Ariyoshi, Koya', None]",PLoS One,,,True
dc55e7876326722cc7c5ad2a88a8d2217c296596,PMC,"The Clinical and Etiological Characteristics of Influenza-Like Illness (ILI) in Outpatients in Shanghai, China, 2011 to 2013",http://dx.doi.org/10.1371/journal.pone.0119513,PMC4379014,25822885,CC BY,"INTRODUCTION: Clinical and etiological characteristics of influenza-like illness (ILI) in outpatients is poorly understood in the southern temperate region of China. We conducted laboratory-based surveillance of viral etiology for ILI outpatients in Shanghai from January 2011 to December 2013. MATERIALS AND METHODS: Clinical and epidemiological data from ILI outpatients, both children and adults, were collected. A total of 1970 nasopharyngeal swabs were collected and tested for 12 respiratory viruses using multiplex RT-PCR, and the data were analyzed anonymously. RESULTS: All 12 respiratory viruses were detected in the specimens. At least one virus was detected in 32.4% of 1970 specimens analyzed, with 1.1% showing co-infections. The most frequently detected agents were influenza A (11.7%), influenza B (9.6%), and rhinoviruses (3.1%).Other viruses were present at a frequency less than 3.0%. We observed a winter peak in the detection rate in ILI patients during 3 years of surveillance and a summer peak in 2012. HCoV, HADV, and HMPV were detected more frequently in children than in adults. Patients infected with influenza virus experienced higher temperatures, more coughs, running noses, headaches and fatigue than patients infected with other viruses and virus-free patients (p<0.001). CONCLUSIONS: The spectrum, seasonality, age distribution and clinical associations of respiratory virus infections in children and adults with influenza-like illness were analyzed in this study for the first time. To a certain extent, the findings can provide baseline data for evaluating the burden of respiratory virus infection in children and adults in Shanghai. It will also provide clinicians with helpful information about the etiological patterns of outpatients presenting with complaints of acute respiratory syndrome, but further studies should be conducted, and longer-term laboratory-based surveillance would give a better picture of the etiology of ILI.",2015 Mar 30,"['Fu, Yifei', 'Pan, Lifeng', 'Sun, Qiao', 'Zhu, Weiping', 'Zhu, Linying', 'Ye, Chuchu', 'Xue, Caoyi', 'Wang, Yuanping', 'Liu, Qing', 'Ma, Ping', 'Qiu, Huifang']",PLoS One,,,True
384dd8bbc85ce35f5da2b0962523fd2870f03d95,PMC,"The Clinical and Etiological Characteristics of Influenza-Like Illness (ILI) in Outpatients in Shanghai, China, 2011 to 2013",http://dx.doi.org/10.1371/journal.pone.0119513,PMC4379014,25822885,CC BY,"INTRODUCTION: Clinical and etiological characteristics of influenza-like illness (ILI) in outpatients is poorly understood in the southern temperate region of China. We conducted laboratory-based surveillance of viral etiology for ILI outpatients in Shanghai from January 2011 to December 2013. MATERIALS AND METHODS: Clinical and epidemiological data from ILI outpatients, both children and adults, were collected. A total of 1970 nasopharyngeal swabs were collected and tested for 12 respiratory viruses using multiplex RT-PCR, and the data were analyzed anonymously. RESULTS: All 12 respiratory viruses were detected in the specimens. At least one virus was detected in 32.4% of 1970 specimens analyzed, with 1.1% showing co-infections. The most frequently detected agents were influenza A (11.7%), influenza B (9.6%), and rhinoviruses (3.1%).Other viruses were present at a frequency less than 3.0%. We observed a winter peak in the detection rate in ILI patients during 3 years of surveillance and a summer peak in 2012. HCoV, HADV, and HMPV were detected more frequently in children than in adults. Patients infected with influenza virus experienced higher temperatures, more coughs, running noses, headaches and fatigue than patients infected with other viruses and virus-free patients (p<0.001). CONCLUSIONS: The spectrum, seasonality, age distribution and clinical associations of respiratory virus infections in children and adults with influenza-like illness were analyzed in this study for the first time. To a certain extent, the findings can provide baseline data for evaluating the burden of respiratory virus infection in children and adults in Shanghai. It will also provide clinicians with helpful information about the etiological patterns of outpatients presenting with complaints of acute respiratory syndrome, but further studies should be conducted, and longer-term laboratory-based surveillance would give a better picture of the etiology of ILI.",2015 Mar 30,"['Fu, Yifei', 'Pan, Lifeng', 'Sun, Qiao', 'Zhu, Weiping', 'Zhu, Linying', 'Ye, Chuchu', 'Xue, Caoyi', 'Wang, Yuanping', 'Liu, Qing', 'Ma, Ping', 'Qiu, Huifang']",PLoS One,,,False
c2b8b47dcfe70db8080da73d7a3941c94b31b025,PMC,Evaluation of ViroCyt(®) Virus Counter for Rapid Filovirus Quantitation,http://dx.doi.org/10.3390/v7030857,PMC4379551,25710889,CC BY,"Development and evaluation of medical countermeasures for diagnostics, vaccines, and therapeutics requires production of standardized, reproducible, and well characterized virus preparations. For filoviruses this includes plaque assay for quantitation of infectious virus, transmission electron microscopy (TEM) for morphology and quantitation of virus particles, and real-time reverse transcription PCR for quantitation of viral RNA (qRT-PCR). The ViroCyt(®) Virus Counter (VC) 2100 (ViroCyt, Boulder, CO, USA) is a flow-based instrument capable of quantifying virus particles in solution. Using a proprietary combination of fluorescent dyes that stain both nucleic acid and protein in a single 30 min step, rapid, reproducible, and cost-effective quantification of filovirus particles was demonstrated. Using a seed stock of Ebola virus variant Kikwit, the linear range of the instrument was determined to be 2.8E+06 to 1.0E+09 virus particles per mL with coefficient of variation ranging from 9.4% to 31.5% for samples tested in triplicate. VC particle counts for various filovirus stocks were within one log of TEM particle counts. A linear relationship was established between the plaque assay, qRT-PCR, and the VC. VC results significantly correlated with both plaque assay and qRT-PCR. These results demonstrated that the VC is an easy, fast, and consistent method to quantify filoviruses in stock preparations.",2015 Feb 20,"['Rossi, Cynthia A.', 'Kearney, Brian J.', 'Olschner, Scott P.', 'Williams, Priscilla L.', 'Robinson, Camenzind G.', 'Heinrich, Megan L.', 'Zovanyi, Ashley M.', 'Ingram, Michael F.', 'Norwood, David A.', 'Schoepp, Randal J.']",Viruses,,,True
b86c0b353d21e4ada6c8cd36da8c433123b23f8e,PMC,Identification of New Respiratory Viruses in the New Millennium,http://dx.doi.org/10.3390/v7030996,PMC4379558,25757061,CC BY,"The rapid advancement of molecular tools in the past 15 years has allowed for the retrospective discovery of several new respiratory viruses as well as the characterization of novel emergent strains. The inability to characterize the etiological origins of respiratory conditions, particularly in children, led several researchers to pursue the discovery of the underlying etiology of disease. In 2001, this led to the discovery of human metapneumovirus (hMPV) and soon following that the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) promoted an increased interest in coronavirology and the latter discovery of human coronavirus (HCoV) NL63 and HCoV-HKU1. Human bocavirus, with its four separate lineages, discovered in 2005, has been linked to acute respiratory tract infections and gastrointestinal complications. Middle East Respiratory Syndrome coronavirus (MERS-CoV) represents the most recent outbreak of a completely novel respiratory virus, which occurred in Saudi Arabia in 2012 and presents a significant threat to human health. This review will detail the most current clinical and epidemiological findings to all respiratory viruses discovered since 2001.",2015 Mar 6,"['Berry, Michael', 'Gamieldien, Junaid', 'Fielding, Burtram C.']",Viruses,,,True
a007977dad90a07b3beb9f689e3be8b3f7d2a7f6,PMC,Advanced Molecular Surveillance of Hepatitis C Virus,http://dx.doi.org/10.3390/v7031153,PMC4379565,25781918,CC BY,"Hepatitis C virus (HCV) infection is an important public health problem worldwide. HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity. This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection. Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings. Therefore, implementation of HCV advanced molecular surveillance (AMS) is essential for disease control. Accounting for virulence is also important for HCV AMS and both viral and host factors contribute to the disease outcome. Therefore, HCV AMS requires the incorporation of host factors as an integral component of the algorithms used to monitor disease occurrence. Importantly, implementation of comprehensive global databases and data mining are also needed for the proper study of the mechanisms responsible for HCV transmission. Here, we review molecular aspects associated with HCV transmission, as well as the most recent technological advances used for virus and host characterization. Additionally, the cornerstone discoveries that have defined the pathway for viral characterization are presented and the importance of implementing advanced HCV molecular surveillance is highlighted.",2015 Mar 13,"['Gonçalves Rossi, Livia Maria', 'Escobar-Gutierrez, Alejandro', 'Rahal, Paula']",Viruses,,,True
75ad8fc2d398fb3440035eb1a565b060c7ce3a04,PMC,Both ERK1 and ERK2 Are Required for Enterovirus 71 (EV71) Efficient Replication,http://dx.doi.org/10.3390/v7031344,PMC4379574,25803100,CC BY,"It has been demonstrated that MEK1, one of the two MEK isoforms in Raf-MEK-ERK1/2 pathway, is essential for successful EV71 propagation. However, the distinct function of ERK1 and ERK2 isoforms, the downstream kinases of MEKs, remains unclear in EV71 replication. In this study, specific ERK siRNAs and selective inhibitor U0126 were applied. Silencing specific ERK did not significantly impact on the EV71-caused biphasic activation of the other ERK isoform, suggesting the EV71-induced activations of ERK1 and ERK2 were non-discriminative and independent to one another. Knockdown of either ERK1 or ERK2 markedly impaired progeny EV71 propagation (both by more than 90%), progeny viral RNA amplification (either by about 30% to 40%) and protein synthesis (both by around 70%), indicating both ERK1 and ERK2 were critical and not interchangeable to EV71 propagation. Moreover, suppression of EV71 replication by inhibiting both early and late phases of ERK1/2 activation showed no significant difference from that of only blocking the late phase, supporting the late phase activation was more importantly responsible for EV71 life cycle. Taken together, this study for the first time identified both ERK1 and ERK2 were required for EV71 efficient replication and further verified the important role of MEK1-ERK1/2 in EV71 replication.",2015 Mar 20,"['Zhu, Meng', 'Duan, Hao', 'Gao, Meng', 'Zhang, Hao', 'Peng, Yihong']",Viruses,,,True
5931dc46426dbfe8457df3f7c0d8ff406810bd23,PMC,Both ERK1 and ERK2 Are Required for Enterovirus 71 (EV71) Efficient Replication,http://dx.doi.org/10.3390/v7031344,PMC4379574,25803100,CC BY,"It has been demonstrated that MEK1, one of the two MEK isoforms in Raf-MEK-ERK1/2 pathway, is essential for successful EV71 propagation. However, the distinct function of ERK1 and ERK2 isoforms, the downstream kinases of MEKs, remains unclear in EV71 replication. In this study, specific ERK siRNAs and selective inhibitor U0126 were applied. Silencing specific ERK did not significantly impact on the EV71-caused biphasic activation of the other ERK isoform, suggesting the EV71-induced activations of ERK1 and ERK2 were non-discriminative and independent to one another. Knockdown of either ERK1 or ERK2 markedly impaired progeny EV71 propagation (both by more than 90%), progeny viral RNA amplification (either by about 30% to 40%) and protein synthesis (both by around 70%), indicating both ERK1 and ERK2 were critical and not interchangeable to EV71 propagation. Moreover, suppression of EV71 replication by inhibiting both early and late phases of ERK1/2 activation showed no significant difference from that of only blocking the late phase, supporting the late phase activation was more importantly responsible for EV71 life cycle. Taken together, this study for the first time identified both ERK1 and ERK2 were required for EV71 efficient replication and further verified the important role of MEK1-ERK1/2 in EV71 replication.",2015 Mar 20,"['Zhu, Meng', 'Duan, Hao', 'Gao, Meng', 'Zhang, Hao', 'Peng, Yihong']",Viruses,,,False
f1a107788ce585f3f5a7daa6b2eaf55997935192,PMC,Fatal disease associated with Swine Hepatitis E virus and Porcine circovirus 2 co-infection in four weaned pigs in China,http://dx.doi.org/10.1186/s12917-015-0375-z,PMC4379595,25889526,CC BY,"BACKGROUND: In recent decades, Porcine circovirus 2 (PCV2) infection has been recognized as the causative agent of postweaning multisystemic wasting syndrome, and has become a threat to the swine industry. Hepatitis E virus (HEV) is another high prevalent pathogen in swine in many regions of the world. PCV2 and HEV are both highly prevalent in pig farms in China. CASE PRESENTATION: In this study, we characterized the HEV and PCV2 co-infection in 2–3 month-old piglets, based on pathogen identification and the pathological changes observed, in Hebei Province, China. The pathological changes were severe, and general hyperemia, hemorrhage, inflammatory cell infiltration, and necrosis were evident in the tissues of dead swine. PCR was used to identify the pathogen and we tested for eight viruses (HEV, Porcine reproductive and respiratory syndrome virus, PCV2, Classical swine fever virus, Porcine epidemic diarrhea virus, Transmissible gastroenteritis coronavirus, Porcine parvovirus and Pseudorabies virus) that are prevalent in Chinese pig farms. The livers, kidneys, spleens, and other organs of the necropsied swine were positive for HEV and/or PCV2. Immunohistochemical staining showed HEV- and PCV2-antigen-positive signals in the livers, kidneys, lungs, lymph nodes, and intestine. CONCLUSION: HEV and PCV2 co-infection in piglets was detected in four out of seven dead pigs from two pig farms in Hebei, China, producing severe pathological changes. The natural co-infection of HEV and PCV2 in pigs in China has rarely been reported. We speculate that co-infection with PCV2 and HEV may bring some negative effect on pig production and recommend that more attention should be paid to this phenomenon.",2015 Mar 26,"['Yang, Yifei', 'Shi, Ruihan', 'She, Ruiping', 'Mao, Jingjing', 'Zhao, Yue', 'Du, Fang', 'Liu, Can', 'Liu, Jianchai', 'Cheng, Minheng', 'Zhu, Rining', 'Li, Wei', 'Wang, Xiaoyang', 'Soomro, Majid Hussain']",BMC Vet Res,,,True
b5ac1d6f75cea098965bf8e6cfe492b1fab346c6,PMC,Molecular characterization and phylogenetic analysis of transmissible gastroenteritis virus HX strain isolated from China,http://dx.doi.org/10.1186/s12917-015-0387-8,PMC4379598,25890036,CC BY,"BACKGROUND: Porcine transmissible gastroenteritis virus (TGEV) is the major etiological agent of viral enteritis and severe diarrhea in suckling piglets. In China, TGEV has caused great economic losses, but its role in epidemic diarrhea is unclear. This study aims to reveal the etiological role of TGEV in piglet diarrhea via molecular characterization and phylogenetic analysis. RESULTS: A TGEV-HX strain was isolated from China, and its complete genome was amplified, cloned, and sequenced. Sequence analysis indicated that it was conserved in the 5′ and 3′-non-translated regions, and there were no insertions or deletions in nonstructural genes, such as ORF1a, ORF1b, ORF3a, ORF3b, and ORF7, as well as in genes encoding structural proteins, such as the envelope (E), membrane (M), and nucleoprotein (N) proteins. Furthermore, the phylogenetic analysis indicated that the TGEV-HX strain was more similar to the TGEV Purdue cluster than to the Miller cluster. CONCLUSIONS: The present study described the isolation and genetic characterization of a TGEV-HX strain. The detailed analysis of the genetic variation of TGEVs in China provides essential information for further understanding the evolution of TGEVs.",2015 Mar 21,"['Hu, Xiaoliang', 'Li, Nannan', 'Tian, Zhige', 'Yin, Xin', 'Qu, Liandong', 'Qu, Juanjuan']",BMC Vet Res,,,True
da26991502da97b746b148ad17cb2b435ef8e0cb,PMC,Genome and Infection Characteristics of Human Parechovirus Type 1: The Interplay between Viral Infection and Type I Interferon Antiviral System,http://dx.doi.org/10.1371/journal.pone.0116158,PMC4380134,25646764,CC BY,"Human parechoviruses (HPeVs), members of the family Picornaviridae, are associated with severe human clinical conditions such as gastrointestinal disease, encephalitis, meningitis, respiratory disease and neonatal sepsis. A new contemporary strain of HPeV1, KVP6 (accession no. KC769584), was isolated from a clinical specimen. Full-genome alignment revealed that HPeV1 KVP6 shares high genome homology with the German strain of HPeV1, 7555312 (accession no. FM178558) and could be classified in the clade 1B group. An intertypic recombination was shown within the P2-P3 genome regions of HPeV1. Cell-type tropism test showed that T84 cells (colon carcinoma cells), A549 cells (lung carcinoma cells) and DBTRG-5MG cells (glioblastoma cells) were susceptible to HPeV1 infection, which might be relevant clinically. A facilitated cytopathic effect and increased viral titers were reached after serial viral passages in Vero cells, with viral genome mutation found in later passages. HPeV1 is sensitive to elevated temperature because 39°C incubation impaired virion production. HPeV1 induced innate immunity with phosphorylation of interferon (IFN) regulatory transcription factor 3 and production of type I IFN in A549 but not T84 cells. Furthermore, type I IFN inhibited HPeV1 production in A549 cells but not T84 cells; T84 cells may be less responsive to type I IFN stimulation. Moreover, HPeV1-infected cells showed downregulated type I IFN activation, which indicated a type I IFN evasion mechanism. The characterization of the complete genome and infection features of HPeV1 provide comprehensive information about this newly isolated HPeV1 for further diagnosis, prevention or treatment strategies.",2015 Feb 3,"['Chang, Jenn-Tzong', 'Yang, Chih-Shiang', 'Chen, Yao-Shen', 'Chen, Bao-Chen', 'Chiang, An-Jen', 'Chang, Yu-Hsiang', 'Tsai, Wei-Lun', 'Lin, You-Sheng', 'Chao, David', 'Chang, Tsung-Hsien']",PLoS One,,,True
8d81ebbd42382fd503dc2aaf88eb5f790ddebe64,PMC,Identify-Isolate-Inform: A Tool for Initial Detection and Management of Measles Patients in the Emergency Department,http://dx.doi.org/10.5811/westjem.2015.3.25678,PMC4380368,25834659,CC BY,"Measles (rubeola) is a highly contagious airborne disease that was declared eliminated in the U.S. in the year 2000. Only sporadic U.S. cases and minor outbreaks occurred until the larger outbreak beginning in 2014 that has become a public health emergency. The “Identify-Isolate-Inform” tool will assist emergency physicians to be better prepared to detect and manage measles patients presenting to the emergency department. Measles typically presents with a prodrome of high fever, and cough/coryza/conjunctivitis, sometimes accompanied by the pathognomonic Koplik spots. Two to four days later, an erythematous maculopapular rash begins on the face and spreads down the body. Suspect patients must be immediately isolated with airborne precautions while awaiting laboratory confirmation of disease. Emergency physicians must rapidly inform the local public health department and hospital infection control personnel of suspected measles cases.",2015 Mar 18,"['Koenig, Kristi L.', 'Alassaf, Wajdan', 'Burns, Michael J.']",West J Emerg Med,,,True
466c7e2cf0d7aae1c4595ce0bb752df2bbaeb033,PMC,Comparison of Schmallenberg virus antibody levels detected in milk and serum from individual cows,http://dx.doi.org/10.1186/s12917-015-0365-1,PMC4381408,25890260,CC BY,"BACKGROUND: Schmallenberg virus (SBV) is a recently emerged virus of ruminants in Europe. Enzyme-linked immunosorbent assays (ELISA) are commonly used to detect SBV-specific antibodies in bulk tank milk samples to monitor herd exposure to infection. However, it has previously been shown that a bulk tank milk sample can test positive even though the majority of cows within the herd are seronegative for SBV antibodies. Development of a pen-side test to detect antibodies in individual milk samples would potentially provide a cheaper test (for which samples are obtained non-invasively) than testing individual serum samples by ELISA. Therefore, the aim of this study was to investigate the agreement between antibody levels measured in milk and serum. RESULTS: Corresponding milk and serum samples from 88 cows in two dairy herds in the UK were tested for presence of immunoglobulin G antibodies to SBV using a commercially-available indirect ELISA. A serum neutralisation test (NT) was also performed as a gold standard assay. The ELISA values obtained for the bulk tank milk samples corresponded with the mean values for individual milk samples from each herd (bulk tank milk values were 58% and 73% and mean individual milk values 50% and 63% for herds A and B, respectively). Of the 88 serum samples tested in the NT, 82 (93%) were positive. Although at higher antibody levels, the ELISA values tended to be higher for the individual milk samples than for the corresponding serum samples, the positive predictive value for milk samples was 98% and for serum samples 94%. The serum ELISA was more likely to give false positive results around the lower cut-off value of the assay. CONCLUSIONS: The results indicate that testing of individual milk samples for antibodies against SBV by ELISA could be used to inform decisions in the management of dairy herds such as which, if any, animals to vaccinate.",2015 Mar 11,"['Daly, Janet M', 'King, Barnabas', 'Tarlinton, Rachael A', 'Gough, Kevin C', 'Maddison, Ben C', 'Blowey, Roger']",BMC Vet Res,,,True
c9708301ac6326b1214f31ab93fcd4b72485cf4b,PMC,GCN5 inhibits XBP-1S-mediated transcription by antagonizing PCAF action,,PMC4381594,25426559,CC BY,"Cellular unfolded protein response (UPR) is induced when endoplasmic reticulum (ER) is under stress. XBP-1S, the active isoform of X-box binding protein 1 (XBP-1), is a key regulator of UPR. Previously, we showed that a histone acetyltransferase (HAT), p300/CBP-associated factor (PCAF), binds to XBP-1S and functions as an activator of XBP-1S. Here, we identify general control nonderepressible 5 (GCN5), a HAT with 73% identity to PCAF, as a novel XBP-1S regulator. Both PCAF and GCN5 bind to the same domain of XBP-1S. Surprisingly, GCN5 potently blocks the XBP-1S-mediated transcription, including cellular UPR genes and latent membrane protein 1 of Epstein-Barr virus. Unlike PCAF, GCN5 acetylates XBP-1S and enhances nuclear retention and protein stability of XBP-1S. However, such GCN5-mediated acetylation of XBP-1S shows no effects on XBP-1S activity. In addition, the HAT activity of GCN5 is not required for repression of XBP-1S target genes. We further demonstrate that GCN5 inhibits XBP-1S-mediated transcription by disrupting the PCAF-XBP-1S interaction and preventing the recruitment of XBP-1S to its target genes. Taken together, our results represent the first work demonstrating that GCN5 and PCAF exhibit different functions and antagonistically regulate the XBP-1S-mediated transcription.",2014 Nov 16,"['Lew, Qiao Jing', 'Chu, Kai Ling', 'Chia, Yi Ling', 'Soo, Benjamin', 'Ho, Jia Pei', 'Ng, Chew Har', 'Kwok, Hui Si', 'Chiang, Cheng-Ming', 'Chang, Yao', 'Chao, Sheng-Hao']",Oncotarget,,,True
7ad58eb8a34fab3f8ca60410bf583454f7c1128a,PMC,GCN5 inhibits XBP-1S-mediated transcription by antagonizing PCAF action,,PMC4381594,25426559,CC BY,"Cellular unfolded protein response (UPR) is induced when endoplasmic reticulum (ER) is under stress. XBP-1S, the active isoform of X-box binding protein 1 (XBP-1), is a key regulator of UPR. Previously, we showed that a histone acetyltransferase (HAT), p300/CBP-associated factor (PCAF), binds to XBP-1S and functions as an activator of XBP-1S. Here, we identify general control nonderepressible 5 (GCN5), a HAT with 73% identity to PCAF, as a novel XBP-1S regulator. Both PCAF and GCN5 bind to the same domain of XBP-1S. Surprisingly, GCN5 potently blocks the XBP-1S-mediated transcription, including cellular UPR genes and latent membrane protein 1 of Epstein-Barr virus. Unlike PCAF, GCN5 acetylates XBP-1S and enhances nuclear retention and protein stability of XBP-1S. However, such GCN5-mediated acetylation of XBP-1S shows no effects on XBP-1S activity. In addition, the HAT activity of GCN5 is not required for repression of XBP-1S target genes. We further demonstrate that GCN5 inhibits XBP-1S-mediated transcription by disrupting the PCAF-XBP-1S interaction and preventing the recruitment of XBP-1S to its target genes. Taken together, our results represent the first work demonstrating that GCN5 and PCAF exhibit different functions and antagonistically regulate the XBP-1S-mediated transcription.",2014 Nov 16,"['Lew, Qiao Jing', 'Chu, Kai Ling', 'Chia, Yi Ling', 'Soo, Benjamin', 'Ho, Jia Pei', 'Ng, Chew Har', 'Kwok, Hui Si', 'Chiang, Cheng-Ming', 'Chang, Yao', 'Chao, Sheng-Hao']",Oncotarget,,,False
4d4b94ef0c1fb8139c207f5cd7fe3037747fd551,PMC,The Placental Protein Syncytin-1 Impairs Antiviral Responses and Exaggerates Inflammatory Responses to Influenza,http://dx.doi.org/10.1371/journal.pone.0118629,PMC4382184,25831059,CC BY,"BACKGROUND: Pregnancy increases susceptibility to influenza. The placenta releases an immunosuppressive endogenous retroviral protein syncytin-1. We hypothesised that exposure of peripheral monocytes (PBMCs) to syncytin-1 would impair responses to H1N1pdm09 influenza. METHODS AND FINDINGS: Recombinant syncytin-1 was produced. PBMCs from non-pregnant women (n=10) were exposed to H1N1pdm09 in the presence and absence of syncytin-1 and compared to responses of PBMCs from pregnant women (n=12). PBMCs were characterised using flow cytometry, release of interferon (IFN)-α, IFN-λ, IFN-γ, IL-10, IL-2, IL-6 and IL-1β were measured by cytometric bead array or ELISA. Exposure of PBMCs to H1N1pdm09 resulted in the release of IFN-α, (14,787 pg/mL, 95% CI 7311-22,264 pg/mL) IFN-λ (1486 pg/mL, 95% CI 756-2216 pg/mL) and IFN-γ (852 pg/mL, 95% CI 193-1511 pg/mL) after 48 hours. This was significantly impaired in pregnant women (IFN-α; p<0.0001 and IFN-λ; p<0.001). Furthermore, in the presence of syncytin-1, PBMCs demonstrated marked reductions in IFN-α and IFN-λ, while enhanced release of IL-10 as well as IL-6 and IL-1β. CONCLUSIONS: Our data indicates that a placental derived protein, syncytin-1 may be responsible for the heightened vulnerability of pregnant women to influenza.",2015 Apr 1,"['Tolosa, Jorge M.', 'Parsons, Kristy S.', 'Hansbro, Philip M.', 'Smith, Roger', 'Wark, Peter A. B.']",PLoS One,,,True
ffa5a409662570035722ecdd262f2b100601da74,PMC,Efficacy and safety of Ban-Lan-Gen granules in the treatment of seasonal influenza: study protocol for a randomized controlled trial,http://dx.doi.org/10.1186/s13063-015-0645-x,PMC4383212,25873046,CC BY,"BACKGROUND: Ban-Lan-Gen (BLG) is a traditional Chinese herbal medicine. It has been used for the prevention and treatment of virus-related respiratory diseases such as influenza virus infection. BLG contains some antiviral compounds, but few evidence-based clinical studies have been conducted to assess its efficacy against influenza. We assessed the effects of BLG (including efficacy and safety) on the treatment of seasonal influenza in an evidence-based clinical trial. METHODS/DESIGN: We conducted a randomized, double-blinded, oseltamivir- and placebo-controlled, parallel-design clinical trial. A total of 177 subjects are going to be recruited after satisfying the criteria: (i) 18 to 65 years of age; (ii) illness onset within 36 h; (3) axillary temperature ≥38.0°C; and (iv) positive influenza (type A/B) virus test. Subjects will be assigned randomly into three groups in equal proportions: oseltamivir treatment, BLG granule treatment, and placebo treatment. Each group receives 5-day treatment and is followed up 1, 3, 5, 7 and 21 days later. Symptoms and patient compliance are recorded, and virus/serum viral antibodies tested. We will use the primary outcome, secondary outcome, and safety indicators to evaluate the efficacy and safety of BLG granules in the treatment of seasonal influenza. DISCUSSION: We have described the first clinical trial for treatment using a single herb against influenza A and B viruses in China. We will hold a large-scale clinical trial to comprehensively evaluate the effectiveness and safety of BLG against influenza infection based on the results of this pilot study. And this clinical trial will serve as an example for the study of other traditional herbal medicines in evidence-based clinical trials. TRIAL REGISTRATION: This study has been registered at ClinicalTrials.gov: NCT02232945 (3 September 2014). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-015-0645-x) contains supplementary material, which is available to authorized users.",2015 Mar 28,"['Li, Zheng-tu', 'Li, Li', 'Chen, Ting-ting', 'Li, Chu-yuan', 'Wang, De-qin', 'Yang, Zi-feng', 'Zhong, Nan-shan']",Trials,,,False
820910bafe8f9bea166fa699f09f71a2c8f28c76,PMC,Efficacy and safety of Ban-Lan-Gen granules in the treatment of seasonal influenza: study protocol for a randomized controlled trial,http://dx.doi.org/10.1186/s13063-015-0645-x,PMC4383212,25873046,CC BY,"BACKGROUND: Ban-Lan-Gen (BLG) is a traditional Chinese herbal medicine. It has been used for the prevention and treatment of virus-related respiratory diseases such as influenza virus infection. BLG contains some antiviral compounds, but few evidence-based clinical studies have been conducted to assess its efficacy against influenza. We assessed the effects of BLG (including efficacy and safety) on the treatment of seasonal influenza in an evidence-based clinical trial. METHODS/DESIGN: We conducted a randomized, double-blinded, oseltamivir- and placebo-controlled, parallel-design clinical trial. A total of 177 subjects are going to be recruited after satisfying the criteria: (i) 18 to 65 years of age; (ii) illness onset within 36 h; (3) axillary temperature ≥38.0°C; and (iv) positive influenza (type A/B) virus test. Subjects will be assigned randomly into three groups in equal proportions: oseltamivir treatment, BLG granule treatment, and placebo treatment. Each group receives 5-day treatment and is followed up 1, 3, 5, 7 and 21 days later. Symptoms and patient compliance are recorded, and virus/serum viral antibodies tested. We will use the primary outcome, secondary outcome, and safety indicators to evaluate the efficacy and safety of BLG granules in the treatment of seasonal influenza. DISCUSSION: We have described the first clinical trial for treatment using a single herb against influenza A and B viruses in China. We will hold a large-scale clinical trial to comprehensively evaluate the effectiveness and safety of BLG against influenza infection based on the results of this pilot study. And this clinical trial will serve as an example for the study of other traditional herbal medicines in evidence-based clinical trials. TRIAL REGISTRATION: This study has been registered at ClinicalTrials.gov: NCT02232945 (3 September 2014). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-015-0645-x) contains supplementary material, which is available to authorized users.",2015 Mar 28,"['Li, Zheng-tu', 'Li, Li', 'Chen, Ting-ting', 'Li, Chu-yuan', 'Wang, De-qin', 'Yang, Zi-feng', 'Zhong, Nan-shan']",Trials,,,False
310122c497498a3be55d1984730142fcf414a4c3,PMC,Efficacy and safety of Ban-Lan-Gen granules in the treatment of seasonal influenza: study protocol for a randomized controlled trial,http://dx.doi.org/10.1186/s13063-015-0645-x,PMC4383212,25873046,CC BY,"BACKGROUND: Ban-Lan-Gen (BLG) is a traditional Chinese herbal medicine. It has been used for the prevention and treatment of virus-related respiratory diseases such as influenza virus infection. BLG contains some antiviral compounds, but few evidence-based clinical studies have been conducted to assess its efficacy against influenza. We assessed the effects of BLG (including efficacy and safety) on the treatment of seasonal influenza in an evidence-based clinical trial. METHODS/DESIGN: We conducted a randomized, double-blinded, oseltamivir- and placebo-controlled, parallel-design clinical trial. A total of 177 subjects are going to be recruited after satisfying the criteria: (i) 18 to 65 years of age; (ii) illness onset within 36 h; (3) axillary temperature ≥38.0°C; and (iv) positive influenza (type A/B) virus test. Subjects will be assigned randomly into three groups in equal proportions: oseltamivir treatment, BLG granule treatment, and placebo treatment. Each group receives 5-day treatment and is followed up 1, 3, 5, 7 and 21 days later. Symptoms and patient compliance are recorded, and virus/serum viral antibodies tested. We will use the primary outcome, secondary outcome, and safety indicators to evaluate the efficacy and safety of BLG granules in the treatment of seasonal influenza. DISCUSSION: We have described the first clinical trial for treatment using a single herb against influenza A and B viruses in China. We will hold a large-scale clinical trial to comprehensively evaluate the effectiveness and safety of BLG against influenza infection based on the results of this pilot study. And this clinical trial will serve as an example for the study of other traditional herbal medicines in evidence-based clinical trials. TRIAL REGISTRATION: This study has been registered at ClinicalTrials.gov: NCT02232945 (3 September 2014). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-015-0645-x) contains supplementary material, which is available to authorized users.",2015 Mar 28,"['Li, Zheng-tu', 'Li, Li', 'Chen, Ting-ting', 'Li, Chu-yuan', 'Wang, De-qin', 'Yang, Zi-feng', 'Zhong, Nan-shan']",Trials,,,True
d8e9ba5b8657f01d92a6da7558aa323fa9ec5539,PMC,Type I Interferon Response Is Delayed in Human Astrovirus Infections,http://dx.doi.org/10.1371/journal.pone.0123087,PMC4383485,25837699,CC BY,"Type I interferon (IFN) activation and its subsequent effects are important in the response to viral infections. Here we show that human astroviruses (HAstVs), which are important agents of acute gastroenteritis in children, induce a mild and delayed IFN response upon infecting CaCo-2 cells. Although IFN-β mRNA is detected within infected cells and supernatant from infected cells show antiviral activity against the replication of other well-known IFN-sensitive viruses, these responses occur at late stages of infection once genome replication has taken place. On the other hand, HAstV replication can be partially reduced by the addition of exogenous IFN, and inhibition of IFN activation by BX795 enhances viral replication, indicating that HAstVs are IFN-sensitive viruses. Finally, different levels of IFN response were observed in cells infected with different HAstV mutants with changes in the hypervariable region of nsP1a/4, suggesting that nsP1a/4 genotype may potentially have clinical implications due to its correlation with the viral replication phenotype and the antiviral responses induced within infected cells.",2015 Apr 2,"['Guix, Susana', 'Pérez-Bosque, Anna', 'Miró, Lluïsa', 'Moretó, Miquel', 'Bosch, Albert', 'Pintó, Rosa M.']",PLoS One,,,True
becb2b5961d536efc8f0a0b535aeaf7e78d3d273,PMC,Sensitivity and Specificity of a Novel Classifier for the Early Diagnosis of Dengue,http://dx.doi.org/10.1371/journal.pntd.0003638,PMC4383489,25836753,CC BY,"BACKGROUND: Dengue is the commonest arboviral disease of humans. An early and accurate diagnosis of dengue can support clinical management, surveillance and disease control and is central to achieving the World Health Organisation target of a 50% reduction in dengue case mortality by 2020. METHODS: 5729 children with fever of <72hrs duration were enrolled into this multicenter prospective study in southern Vietnam between 2010-2012. A composite of gold standard diagnostic tests identified 1692 dengue cases. Using statistical methods, a novel Early Dengue Classifier (EDC) was developed that used patient age, white blood cell count and platelet count to discriminate dengue cases from non-dengue cases. RESULTS: The EDC had a sensitivity of 74.8% (95%CI: 73.0-76.8%) and specificity of 76.3% (95%CI: 75.2-77.6%) for the diagnosis of dengue. As an adjunctive test alongside NS1 rapid testing, sensitivity of the composite test was 91.6% (95%CI: 90.4-92.9%). CONCLUSIONS: We demonstrate that the early diagnosis of dengue can be enhanced beyond the current standard of care using a simple evidence-based algorithm. The results should support patient management and clinical trials of specific therapies.",2015 Apr 2,"['Tuan, Nguyen Minh', 'Nhan, Ho Thi', 'Chau, Nguyen Van Vinh', 'Hung, Nguyen Thanh', 'Tuan, Ha Manh', 'Tram, Ta Van', 'Ha, Nguyen Le Da', 'Loi, Phan', 'Quang, Han Khoi', 'Kien, Duong Thi Hue', 'Hubbard, Sonya', 'Chau, Tran Nguyen Bich', 'Wills, Bridget', 'Wolbers, Marcel', 'Simmons, Cameron P.']",PLoS Negl Trop Dis,,,True
29e893a01ad314a8432d5948be971e13e48b9103,PMC,A Rational Approach to Estimating the Surgical Demand Elasticity Needed to Guide Manpower Reallocation during Contagious Outbreaks,http://dx.doi.org/10.1371/journal.pone.0122625,PMC4383619,25837596,CC BY,"BACKGROUND: Emerging infectious diseases continue to pose serious threats to global public health. So far, however, few published study has addressed the need for manpower reallocation needed in hospitals when such a serious contagious outbreak occurs. AIM: To quantify the demand elasticity of the major surgery types in order to guide future manpower reallocation during contagious outbreaks. MATERIALS AND METHODS: Based on a nationwide research database in Taiwan, we extracted the monthly volumes of major surgery types for the period 1998–2003, which covered the SARS period, in order to carry out a time series analysis. The demand elasticity of each surgery type was then estimated by autoregressive integrated moving average (ARIMA) analysis. RESULTS: During the study period, the surgical volumes of most selected surgery types either increased or remained steady. We categorized these surgery types into low-, moderate- and high-elastic groups according to their demand elasticity. Appendectomy, ‘open reduction of fracture with internal fixation’ and ‘free skin graft’ were in the low demand elasticity group. Transurethral prostatectomy and extracorporeal shockwave lithotripsy (ESWL) were in the high demand elasticity group. The manpower of the departments carrying out the surgeries with low demand elasticity should be maintained during outbreaks. In contrast, departments in charge of surgeries mainly with high demand elasticity, like urology departments, may be in a position to have part of their staff reallocated. CONCLUSIONS: Taking advantage of the demand variation during the SARS period in 2003, we adopted the concept of demand elasticity and used a time series approach to figure out an effective index of demand elasticity for various types of surgery that could be used as a rational reference to carry out manpower reallocation during contagious outbreak situations.",2015 Apr 2,"['Tsao, Hsiao-Mei', 'Sun, Ying-Chou', 'Liou, Der-Ming']",PLoS One,,,True
b81a921bc4d2223e69b7fddf4f1d2a3ba7622f92,PMC,Transcriptional Regulation of Chemokine Expression in Ovarian Cancer,http://dx.doi.org/10.3390/biom5010223,PMC4384120,25790431,CC BY,"The increased expression of pro-inflammatory and pro-angiogenic chemokines contributes to ovarian cancer progression through the induction of tumor cell proliferation, survival, angiogenesis, and metastasis. The substantial potential of these chemokines to facilitate the progression and metastasis of ovarian cancer underscores the need for their stringent transcriptional regulation. In this Review, we highlight the key mechanisms that regulate the transcription of pro-inflammatory chemokines in ovarian cancer cells, and that have important roles in controlling ovarian cancer progression. We further discuss the potential mechanisms underlying the increased chemokine expression in drug resistance, along with our perspective for future studies.",2015 Mar 17,"['Singha, Bipradeb', 'Gatla, Himavanth R.', 'Vancurova, Ivana']",Biomolecules,,,True
ad4f830c6a0985b878a66d4e797232ccba91aedc,PMC,Targeting a ribonucleoprotein complex containing the caprin-1 protein and the c-Myc mRNA suppresses tumor growth in mice: an identification of a novel oncotarget,,PMC4385842,25669982,CC BY,"Tylophorine compounds have been the focus of drug development for decades. Tylophorine derivatives exhibit anti-cancer activities but their cellular targets remain unknown. We used a biotinylated tylophorine derivative to probe for the interacting cellular target(s) of tylophorine. Tylophorine directly binds to caprin-1 and consequently enhances the recruitment of G3BP1, c-Myc mRNA, and cyclin D2 mRNA to form a ribonucleoprotein complex. Subsequently, this tylophorine targeted ribonucleoprotein complex is sequestered to the polysomal fractions and the protein expressions of the associated mRNA-transcripts are repressed. Caprin-1 depleted carcinoma cells become more resistant to tylophorine, associated with decreased formation of the ribonucleoprotein complex targeted by tylophorine. Consequently, tylophorine downregulates c-Myc and cyclins D1/D2, causing hypophosphorylation of Rb and suppression of both processing-body formation and the Warburg effect. Gene expression profiling and gain-of-c-Myc-function experiments also revealed that the downregulated c-Myc contributes to the anti-oncogenic effects of tylophorine compounds. Furthermore, the potent tylophorine derivative dibenzoquinoline-33b elicited a similar effect, as c-Myc protein levels were also decreased in xenograft tumors treated with dibenzoquinoline-33b. Thus, tylophorine compounds exert anti-cancer activity predominantly by targeting and sequestering the caprin-1 protein and c-Myc mRNA associated ribonucleoprotein complex.",2014 Dec 10,"['Qiu, Ya-Qi', 'Yang, Cheng-Wei', 'Lee, Yue-Zhi', 'Yang, Ruey-Bing', 'Lee, Chih-Hao', 'Hsu, Hsing-Yu', 'Chang, Chien-Chung', 'Lee, Shiow-Ju']",Oncotarget,,,True
9de48553eac5b5676f0e796f544e04634d39aaa4,PMC,Targeting a ribonucleoprotein complex containing the caprin-1 protein and the c-Myc mRNA suppresses tumor growth in mice: an identification of a novel oncotarget,,PMC4385842,25669982,CC BY,"Tylophorine compounds have been the focus of drug development for decades. Tylophorine derivatives exhibit anti-cancer activities but their cellular targets remain unknown. We used a biotinylated tylophorine derivative to probe for the interacting cellular target(s) of tylophorine. Tylophorine directly binds to caprin-1 and consequently enhances the recruitment of G3BP1, c-Myc mRNA, and cyclin D2 mRNA to form a ribonucleoprotein complex. Subsequently, this tylophorine targeted ribonucleoprotein complex is sequestered to the polysomal fractions and the protein expressions of the associated mRNA-transcripts are repressed. Caprin-1 depleted carcinoma cells become more resistant to tylophorine, associated with decreased formation of the ribonucleoprotein complex targeted by tylophorine. Consequently, tylophorine downregulates c-Myc and cyclins D1/D2, causing hypophosphorylation of Rb and suppression of both processing-body formation and the Warburg effect. Gene expression profiling and gain-of-c-Myc-function experiments also revealed that the downregulated c-Myc contributes to the anti-oncogenic effects of tylophorine compounds. Furthermore, the potent tylophorine derivative dibenzoquinoline-33b elicited a similar effect, as c-Myc protein levels were also decreased in xenograft tumors treated with dibenzoquinoline-33b. Thus, tylophorine compounds exert anti-cancer activity predominantly by targeting and sequestering the caprin-1 protein and c-Myc mRNA associated ribonucleoprotein complex.",2014 Dec 10,"['Qiu, Ya-Qi', 'Yang, Cheng-Wei', 'Lee, Yue-Zhi', 'Yang, Ruey-Bing', 'Lee, Chih-Hao', 'Hsu, Hsing-Yu', 'Chang, Chien-Chung', 'Lee, Shiow-Ju']",Oncotarget,,,True
3bc7abde53bcbdc7ca555c835d5ad34a67941a80,PMC,"The eEF1A Proteins: At the Crossroads of Oncogenesis, Apoptosis, and Viral Infections",http://dx.doi.org/10.3389/fonc.2015.00075,PMC4387925,25905039,CC BY,"Eukaryotic translation elongation factors 1 alpha, eEF1A1 and eEF1A2, are not only translation factors but also pleiotropic proteins that are highly expressed in human tumors, including breast cancer, ovarian cancer, and lung cancer. eEF1A1 modulates cytoskeleton, exhibits chaperone-like activity and also controls cell proliferation and cell death. In contrast, eEF1A2 protein favors oncogenesis as shown by the fact that overexpression of eEF1A2 leads to cellular transformation and gives rise to tumors in nude mice. The eEF1A2 protein stimulates the phospholipid signaling and activates the Akt-dependent cell migration and actin remodeling that ultimately favors tumorigenesis. In contrast, inactivation of eEF1A proteins leads to immunodeficiency, neural and muscular defects, and favors apoptosis. Finally, eEF1A proteins interact with several viral proteins resulting in enhanced viral replication, decreased apoptosis, and increased cellular transformation. This review summarizes the recent findings on eEF1A proteins indicating that eEF1A proteins play a critical role in numerous human diseases through enhancement of oncogenesis, blockade of apoptosis, and increased viral pathogenesis.",2015 Apr 7,"['Abbas, Wasim', 'Kumar, Amit', 'Herbein, Georges']",Front Oncol,,,True
c3334a3ad6a9e88664342aff618229775fb3e31a,PMC,Leukocyte-Derived IFN-α/β and Epithelial IFN-λ Constitute a Compartmentalized Mucosal Defense System that Restricts Enteric Virus Infections,http://dx.doi.org/10.1371/journal.ppat.1004782,PMC4388470,25849543,CC BY,"Epithelial cells are a major port of entry for many viruses, but the molecular networks which protect barrier surfaces against viral infections are incompletely understood. Viral infections induce simultaneous production of type I (IFN-α/β) and type III (IFN-λ) interferons. All nucleated cells are believed to respond to IFN-α/β, whereas IFN-λ responses are largely confined to epithelial cells. We observed that intestinal epithelial cells, unlike hematopoietic cells of this organ, express only very low levels of functional IFN-α/β receptors. Accordingly, after oral infection of IFN-α/β receptor-deficient mice, human reovirus type 3 specifically infected cells in the lamina propria but, strikingly, did not productively replicate in gut epithelial cells. By contrast, reovirus replicated almost exclusively in gut epithelial cells of IFN-λ receptor-deficient mice, suggesting that the gut mucosa is equipped with a compartmentalized IFN system in which epithelial cells mainly respond to IFN-λ that they produce after viral infection, whereas other cells of the gut mostly rely on IFN-α/β for antiviral defense. In suckling mice with IFN-λ receptor deficiency, reovirus replicated in the gut epithelium and additionally infected epithelial cells lining the bile ducts, indicating that infants may use IFN-λ for the control of virus infections in various epithelia-rich tissues. Thus, IFN-λ should be regarded as an autonomous virus defense system of the gut mucosa and other epithelial barriers that may have evolved to avoid unnecessarily frequent triggering of the IFN-α/β system which would induce exacerbated inflammation.",2015 Apr 7,"['Mahlakõiv, Tanel', 'Hernandez, Pedro', 'Gronke, Konrad', 'Diefenbach, Andreas', 'Staeheli, Peter']",PLoS Pathog,,,True
c90c4e5ca7134a20586234aae4f4f8b6b42c05fe,PMC,Unlocking Patients with Mental Disorders Who Were in Restraints at Home: A National Follow-Up Study of China’s New Public Mental Health Initiatives,http://dx.doi.org/10.1371/journal.pone.0121425,PMC4388503,25848800,CC BY,"BACKGROUND: In 2005, China implemented a demonstration program known as “686” to scale-up nation-wide basic mental health services designed to improve access to evidence-based care and to promote human rights for people with severe mental disorders. As part of the 686 Program, teams “unlocked” and provided continuous mental health care to people with severe mental disorders who were found in restraints and largely untreated in their family homes. We implemented a nation-wide two-stage follow-up study to measure the effectiveness and sustainability of the “unlocking and treatment” intervention and its impact on the well-being of patients’ families. METHODS: 266 patients unlocked from 2005 in “686” demonstration sites across China were recruited in Stage One of the study in 2009. In 2012, 230 of the 266 cases were re-interviewed (the Stage Two study). Outcome measures included the patient medication adherence and social functioning, family burden ratings, and relocking rate. We utilized pre-post tests to analyze the changes over time following the unlocking efforts. RESULTS: 96% of patients were diagnosed with schizophrenia. Prior to unlocking, their total time locked ranged from two weeks to 28 years, with 32% having been locked multiple times. The number of persons regularly taking medicines increased from one person at the time of unlocking to 74% in 2009 and 76% in 2012. Pre-post tests showed sustained improvement in patient social functioning and significant reductions in family burden. Over 92% of patients remained free of restraints in 2012. CONCLUSION: Practice-based evidence from our study suggests an important model for protecting the human rights of people with mental disorders and keeping them free of restraints can be achieved by providing accessible, community based mental health services with continuity of care. China’s “686” Program can inform similar efforts in low-resource settings where community locking of patients is practiced.",2015 Apr 7,"['Guan, Lili', 'Liu, Jin', 'Wu, Xia Min', 'Chen, Dafang', 'Wang, Xun', 'Ma, Ning', 'Wang, Yan', 'Good, Byron', 'Ma, Hong', 'Yu, Xin', 'Good, Mary-Jo']",PLoS One,,,True
8111c472b27463ca0dfae56c5196eb4c92fdd14f,PMC,Studying the effect of chloroquine on sporozoite-induced protection and immune responses in Plasmodium berghei malaria,http://dx.doi.org/10.1186/s12936-015-0626-2,PMC4389414,25889324,CC BY,"BACKGROUND: Sporozoite immunization of animals and humans under a chemo-prophylactic cover of chloroquine (CPS-CQ) efficiently induces sterile protection against malaria. In humans, CPS-CQ is strikingly more efficient than immunization with radiation attenuated sporozoites (RAS), raising the hypothesis that this might be partially due to CQ. Chloroquine, an established anti-malarial drug, is also well known for its immune modulating properties including improvement of cross-presentation. The aim of this study was to investigate whether co-administration of CQ during sporozoite immunization improves cellular responses and protective efficacy in Plasmodium berghei models. METHODS: A number of experiments in selected complimentary P. berghei murine models in Balb/cByJ and C57BL/6j mice was performed. First, the effect of CQ administration on the induction of protection and immune responses by RAS immunization was studied. Next, the effect of CQ on the induction of circumsporozoite (CS) protein-specific CD8(+) T cells by immunization with P. berghei parasites expressing a mutant CS protein was investigated. Finally, a direct comparison of CPS-CQ to CPS with mefloquine (MQ), an anti-malarial with little known immune modulating effects, was performed. RESULTS: When CQ was co-administered during immunization with graded numbers of RAS, this did not lead to an increase in frequencies of total memory CD8(+) T cells or CS protein-specific CD8(+) T cells. Also parasite-specific cytokine production and protection remained unaltered. Replacement of CQ by MQ for CPS immunization resulted in significantly reduced percentages of IFNγ producing memory T cells in the liver (p = 0.01), but similar protection. CONCLUSIONS: This study does not provide evidence for a direct beneficial effect of CQ on the induction of sporozoite-induced immune responses and protection in P. berghei malaria models. Alternatively, the higher efficiency of CPS compared to RAS might be explained by an indirect effect of CQ through limiting blood-stage exposure after immunization or to increased antigen exposure and, therefore, improved breadth of the immune response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-015-0626-2) contains supplementary material, which is available to authorized users.",2015 Mar 26,"['Bijker, Else M', 'Nganou-Makamdop, Krystelle', 'van Gemert, Geert-Jan', 'Zavala, Fidel', 'Cockburn, Ian', 'Sauerwein, Robert W']",Malar J,,,True
fdd420ba12ea83c4db57fccfe77d5aad622db3c6,PMC,Analysis of Chemokines and Receptors Expression Profile in the Myelin Mutant Taiep Rat,http://dx.doi.org/10.1155/2015/397310,PMC4390177,25883747,CC BY,"Taiep rat has a failure in myelination and remyelination processes leading to a state of hypomyelination throughout its life. Chemokines, which are known to play a role in inflammation, are also involved in the remyelination process. We aimed to demonstrate that remyelination-stimulating factors are altered in the brainstem of 1- and 6-month-old taiep rats. We used a Rat RT(2) Profiler PCR Array to assess mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors. We also evaluated protein levels of CCL2, CCR1, CCR2, CCL5, CCR5, CCR8, CXCL1, CXCR2, CXCR4, FGF2, and VEGFA by ELISA. Sprague-Dawley rats were used as a control. PCR Array procedure showed that proinflammatory cytokines were not upregulated in the taiep rat. In contrast, some mRNA levels of beta and alpha chemokines were upregulated in 1-month-old rats, but CXCR4 was downregulated at their 6 months of age. ELISA results showed that CXCL1, CCL2, CCR2, CCR5, CCR8, and CXCR4 protein levels were decreased in brainstem at the age of 6 months. These results suggest the presence of a chronic neuroinflammation process with deficiency of remyelination-stimulating factors (CXCL1, CXCR2, and CXCR4), which might account for the demyelination in the taiep rat.",2015 Mar 25,"['Soto-Rodriguez, Guadalupe', 'Gonzalez-Barrios, Juan-Antonio', 'Martinez-Fong, Daniel', 'Blanco-Alvarez, Victor-Manuel', 'Eguibar, Jose R.', 'Ugarte, Araceli', 'Martinez-Perez, Francisco', 'Brambila, Eduardo', 'Millán-Perez Peña, Lourdes', 'Pazos-Salazar, Nidia-Gary', 'Torres-Soto, Maricela', 'Garcia-Robles, Guadalupe', 'Tomas-Sanchez, Constantino', 'Leon-Chavez, Bertha Alicia']",Oxid Med Cell Longev,,,True
3725a278a669559c9fd096a9a7dd5f35c6928c6c,PMC,Target-Dependent Enrichment of Virions Determines the Reduction of High-Throughput Sequencing in Virus Discovery,http://dx.doi.org/10.1371/journal.pone.0122636,PMC4390369,25853649,CC BY,"Viral infections cause many different diseases stemming both from well-characterized viral pathogens but also from emerging viruses, and the search for novel viruses continues to be of great importance. High-throughput sequencing is an important technology for this purpose. However, viral nucleic acids often constitute a minute proportion of the total genetic material in a sample from infected tissue. Techniques to enrich viral targets in high-throughput sequencing have been reported, but the sensitivity of such methods is not well established. This study compares different library preparation techniques targeting both DNA and RNA with and without virion enrichment. By optimizing the selection of intact virus particles, both by physical and enzymatic approaches, we assessed the effectiveness of the specific enrichment of viral sequences as compared to non-enriched sample preparations by selectively looking for and counting read sequences obtained from shotgun sequencing. Using shotgun sequencing of total DNA or RNA, viral targets were detected at concentrations corresponding to the predicted level, providing a foundation for estimating the effectiveness of virion enrichment. Virion enrichment typically produced a 1000-fold increase in the proportion of DNA virus sequences. For RNA virions the gain was less pronounced with a maximum 13-fold increase. This enrichment varied between the different sample concentrations, with no clear trend. Despite that less sequencing was required to identify target sequences, it was not evident from our data that a lower detection level was achieved by virion enrichment compared to shotgun sequencing.",2015 Apr 8,"['Jensen, Randi Holm', 'Mollerup, Sarah', 'Mourier, Tobias', 'Hansen, Thomas Arn', 'Fridholm, Helena', 'Nielsen, Lars Peter', 'Willerslev, Eske', 'Hansen, Anders Johannes', 'Vinner, Lasse']",PLoS One,,,True
5c8e391286fba644689754596eaf50c7f32b5a99,PMC,Molecular Typing and Epidemiology Profiles of Human Adenovirus Infection among Paediatric Patients with Severe Acute Respiratory Infection in China,http://dx.doi.org/10.1371/journal.pone.0123234,PMC4391708,25856575,CC BY,"BACKGROUND: Human adenoviruses (HAdVs) have been recognised as pathogens that cause a broad spectrum of diseases. The studies on HAdV infection among children with severe acute respiratory infection (SARI) are limited. OBJECTIVE: To investigate the prevalence, epidemiology, and genotype of HAdV among children with SARI in China. STUDY DESIGN: Nasopharyngeal aspirates (NPAs) or induced sputum (IS) was collected from hospitalised children with SARIs in Beijing (representing Northern China; n = 259) and Zhejiang Province (representing Eastern China; n = 293) from 2007 to 2010. The prevalence of HAdV was screened by polymerase chain reaction (PCR), followed by sequence typing of PCR fragments that targeted the second half of the hexon gene. In addition, co-infection with other human respiratory viruses, related epidemiological profiles and clinical presentations were investigated. RESULTS AND CONCLUSIONS: In total, 76 (13.8%) of 552 SARI patients were positive for HAdV, and the infection rates of HAdV in Northern and Eastern China were 20.1% (n = 52) and 8.2% (n = 24), respectively. HAdV co-infection with other respiratory viruses was frequent (infection rates: Northern China, 90.4%; Eastern China, 70.8%). The peak seasons for HAdV-B infection was winter and spring. Additionally, members of multiple species (Human mastadenovirus B, C, D and E) were circulating among paediatric patients with SARI, of which HAdV-B (34/52; 65.4%) and HAdV-C (20/24, 83.3%) were the most predominant in Northern and Eastern China, respectively. These findings provide a benchmark for future epidemiology and prevention strategies for HAdV.",2015 Apr 9,"['Li, Yamin', 'Zhou, Weimin', 'Zhao, Yanjie', 'Wang, Yanqun', 'Xie, Zhengde', 'Lou, Yongliang', 'Tan, Wenjie']",PLoS One,,,True
f0f627b8e856fdf97cf414ac42f3536ff1a33134,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,True
4a23c60bc6b2ad215c359eb1cde0e39a02f1c58b,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
35441dbff544552c333248073f7b607d589dcf11,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
81218b498d85bed08aed26f5528388196e18347f,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
066c2d87d87b962f50259df3f1c7ef90cf71f552,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
8738048c7fa1a4002ac20dd884f60549188a7bc5,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
4123be6939693b4b61698ad16390726cde1f8e83,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
a728bd8a56bd0a774f87937ee40356882fbe363e,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
73d99b38d24686662faa3bb28bdcd5596e945b2d,PMC,Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques,http://dx.doi.org/10.1371/journal.pone.0122835,PMC4391709,25856308,CC BY,"HIV-1-specific CD4(+) and CD8(+) T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4(+) T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8(+) T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4(+) and CD8(+) T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4(+) T cells. Approximately 50% of AdC7-GRN-induced memory CD8(+) T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4(+) and CD8(+) T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4(+) and CD8(+) T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4(+) T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.",2015 Apr 9,"['Lorin, Clarisse', 'Vanloubbeeck, Yannick', 'Baudart, Sébastien', 'Ska, Michaël', 'Bayat, Babak', 'Brauers, Geoffroy', 'Clarinval, Géraldine', 'Donner, Marie-Noëlle', 'Marchand, Martine', 'Koutsoukos, Marguerite', 'Mettens, Pascal', 'Cohen, Joe', 'Voss, Gerald']",PLoS One,,,False
7ed7b23c66b9c4ad156f37619f8b88bc1c1e996b,PMC,Age-Related Onset of Obesity Corresponds with Metabolic Dysregulation and Altered Microglia Morphology in Mice Deficient for Ifitm Proteins,http://dx.doi.org/10.1371/journal.pone.0123218,PMC4391874,25856311,CC0,"The IfitmDel mouse lacks all five of the Ifitm genes via LoxP deletion. This animal breeds normally with no obvious defect in development. The IfitmDel animals exhibit a steady and significantly enhanced weight gain relative to wild-type controls beginning about three months of age and under normal feeding conditions. The increased weight corresponds with elevated fat mass, and in tolerance tests they are hyporesponsive to insulin but respond normally to glucose. Both young (4 mo) and older (12 mo) IfitmDel mice have enhanced levels of serum leptin suggesting a defect in leptin/leptin receptor signaling. Analysis of the gene expression profiles in the hypothalamus of IfitmDel animals, compared to WT, demonstrated an altered ratio of Pomc and Npy neuropeptide expression, which likely impairs the satiation response of the IfitmDel animal leading to an increased eating behavior. Also elevated in hypothalamus of IfitmDel mice were pro-inflammatory cytokine expression and reduced IL-10. Anatomical analysis of the hypothalamus using immunohistochemistry revealed that microglia exhibit an abnormal morphology in IfitmDel animals and respond abnormally to Poly:IC challenge. These abnormalities extend the phenotype of the IfitmDel mouse beyond abnormal responses to viral challenge to include a metabolic phenotype and weight gain. Further, this novel phenotype for the IfitmDel mouse could be related to abnormal neuropeptide production, inflammatory status and microglia status in the hypothalamus.",2015 Apr 9,"['Wee, Yin Shen', 'Weis, Janis J.', 'Gahring, Lorise C.', 'Rogers, Scott W.', 'Weis, John H.']",PLoS One,,,True
7b22c0d8cb7675bcc5aa283fe3bfef6c72052519,PMC,Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV),http://dx.doi.org/10.1371/journal.pone.0123126,PMC4391951,25856093,CC0,"The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens.",2015 Apr 9,"['Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Kumar, Mia R.', 'Johnson, Reed F.', 'Hensley, Lisa E.', 'Ellington, Andrew D.']",PLoS One,,,True
638b85191a280fd443ab5cae740b18d9c7a33111,PMC,Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV),http://dx.doi.org/10.1371/journal.pone.0123126,PMC4391951,25856093,CC0,"The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens.",2015 Apr 9,"['Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Kumar, Mia R.', 'Johnson, Reed F.', 'Hensley, Lisa E.', 'Ellington, Andrew D.']",PLoS One,,,False
57ba11d45980a89cf1313f3eab68ad0c77d53439,PMC,Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV),http://dx.doi.org/10.1371/journal.pone.0123126,PMC4391951,25856093,CC0,"The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens.",2015 Apr 9,"['Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Kumar, Mia R.', 'Johnson, Reed F.', 'Hensley, Lisa E.', 'Ellington, Andrew D.']",PLoS One,,,False
ad3f041570cc2b3f4ba0b08e97f03ded08785a03,PMC,Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV),http://dx.doi.org/10.1371/journal.pone.0123126,PMC4391951,25856093,CC0,"The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens.",2015 Apr 9,"['Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Kumar, Mia R.', 'Johnson, Reed F.', 'Hensley, Lisa E.', 'Ellington, Andrew D.']",PLoS One,,,False
d45dd40806dfbd1ca6504db7fc56dc775aff31bc,PMC,Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV),http://dx.doi.org/10.1371/journal.pone.0123126,PMC4391951,25856093,CC0,"The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens.",2015 Apr 9,"['Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Kumar, Mia R.', 'Johnson, Reed F.', 'Hensley, Lisa E.', 'Ellington, Andrew D.']",PLoS One,,,False
2fd9cf0a1317d136ce3e0a14b71cffb6d74e257e,PMC,Real-Time Sequence-Validated Loop-Mediated Isothermal Amplification Assays for Detection of Middle East Respiratory Syndrome Coronavirus (MERS-CoV),http://dx.doi.org/10.1371/journal.pone.0123126,PMC4391951,25856093,CC0,"The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF)1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD) for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU) (5 to 50 PFU/ml) of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens.",2015 Apr 9,"['Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Kumar, Mia R.', 'Johnson, Reed F.', 'Hensley, Lisa E.', 'Ellington, Andrew D.']",PLoS One,,,False
dd40ad3eec9f455f6ab725f007eb32e852b3439c,PMC,Identification of Appropriate Reference Genes for qRT-PCR Analysis of Heat-Stressed Mammary Epithelial Cells in Riverine Buffaloes (Bubalus bubalis),http://dx.doi.org/10.5402/2013/735053,PMC4393032,25937980,CC BY,"Gene expression studies require appropriate normalization methods for proper evaluation of reference genes. To date, not many studies have been reported on the identification of suitable reference genes in buffaloes. The present study was undertaken to determine the panel of suitable reference genes in heat-stressed buffalo mammary epithelial cells (MECs). Briefly, MEC culture from buffalo mammary gland was exposed to 42 °C for one hour and subsequently allowed to recover at 37 °C for different time intervals (from 30 m to 48 h). Three different algorithms, geNorm, NormFinder, and BestKeeper softwares, were used to evaluate the stability of 16 potential reference genes from different functional classes. Our data identified RPL4, EEF1A1, and RPS23 genes to be the most appropriate reference genes that could be utilized for normalization of qPCR data in heat-stressed buffalo MECs.",2013 Jan 28,"['Kapila, Neha', 'Kishore, Amit', 'Sodhi, Monika', 'Sharma, Ankita', 'Kumar, Pawan', 'Mohanty, A. K.', 'Jerath, Tanushri', 'Mukesh, M.']",ISRN Biotechnol,,,True
e2de7af2f055e3cf79556848d5b6aa2d27c4b97d,PMC,Antiviral Activity and Possible Mechanism of Action of Constituents Identified in Paeonia lactiflora Root toward Human Rhinoviruses,http://dx.doi.org/10.1371/journal.pone.0121629,PMC4393083,25860871,CC BY,"Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cost billions of USD annually in medical visits and missed school and work. An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results were compared with those of a reference control ribavirin. Based on 50% inhibitory concentration values, PGG was 13.4 and 18.0 times more active toward HRV-2 (17.89 μM) and HRV-4 (17.33 μM) in MRC5 cells, respectively, than ribavirin. The constituents had relatively high selective index values (3.3–>8.5). The 100 μg/mL PA and 20 μg/mL PGG did not interact with the HRV-4 particles. These constituents inhibited HRV-4 infection only when they were added during the virus inoculation (0 h), the adsorption period of HRVs, but not after 1 h or later. Moreover, the RNA replication levels of HRVs were remarkably reduced in the MRC5 cultures treated with these constituents. These findings suggest that PGG and PA may block or reduce the entry of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play an important role in interfering with expressions of rhinovirus receptors (intercellular adhesion molecule-1 and low-density lipoprotein receptor), inflammatory cytokines (interleukin (IL)-6, IL-8, tumor necrosis factor, interferon beta, and IL-1β), and Toll-like receptor, which resulted in diminishing symptoms induced by HRV. Global efforts to reduce the level of synthetic drugs justify further studies on P. lactiflora root-derived materials as potential anti-HRV products or lead molecules for the prevention or treatment of HRV.",2015 Apr 10,"['Ngan, Luong Thi My', 'Jang, Myeong Jin', 'Kwon, Min Jung', 'Ahn, Young Joon']",PLoS One,,,True
e854283ba0d428f16fb5eec6a1ba210ff7925125,PMC,Human alveolar epithelial type II cells in primary culture,http://dx.doi.org/10.14814/phy2.12288,PMC4393197,25677546,CC BY,"Alveolar epithelial type II (AEII) cells are a key structure and defender in the lung but also are the targets in many lung diseases, including acute respiratory distress syndrome, ventilator-induced lung injury, and pulmonary fibrosis. We sought to establish an optimized method for high yielding and long maintenance of characteristics of primary human AEII cells to facilitate the investigation of the mechanisms of lung diseases at the cellular and molecular levels. Adult human peripheral normal lung tissues of oncologic patients undergoing lung resection were collected. The AEII cells were isolated and identified by the expression of pro-surfactant protein (SP)C, epithelial sodium channel (αENaC) and cytokeratin (CK)-8, the lamellar bodies specific for AEII cells, and confirmed by the histology using electron microscopy. The phenotype of AEII cells was characterized by the expression of surfactant proteins (SP-A, SP-B, SP-C, SP-D), CK-8, KL-6, αENaC, and aquaporin (AQP)-3, which was maintained over 20 days. The biological activity of the primary human AEII cells producing SP-C, cytokines, and intercellular adhesion molecule-1 was vigorous in response to stimulation with tumor necrosis factor-α. We have modified previous methods and optimized a method for isolation of high purity and long maintenance of the human AEII cell phenotype in primary culture. This method provides an important tool for studies aiming at elucidating the molecular mechanisms of lung diseases exclusively in AEII cells.",2015 Feb 13,"['Mao, Pu', 'Wu, Songling', 'Li, Jianchun', 'Fu, Wei', 'He, Weiqun', 'Liu, Xiaoqing', 'Slutsky, Arthur S', 'Zhang, Haibo', 'Li, Yimin']",Physiol Rep,,,True
8e8e5b1a4c76cea327ba95e100445f08ffebf9be,PMC,Characterizing the Transmission Potential of Zoonotic Infections from Minor Outbreaks,http://dx.doi.org/10.1371/journal.pcbi.1004154,PMC4393285,25860289,CC BY,"The transmission potential of a novel infection depends on both the inherent transmissibility of a pathogen, and the level of susceptibility in the host population. However, distinguishing between these pathogen- and population-specific properties typically requires detailed serological studies, which are rarely available in the early stages of an outbreak. Using a simple transmission model that incorporates age-stratified social mixing patterns, we present a novel method for characterizing the transmission potential of subcritical infections, which have effective reproduction number R<1, from readily available data on the size of outbreaks. We show that the model can identify the extent to which outbreaks are driven by inherent pathogen transmissibility and pre-existing population immunity, and can generate unbiased estimates of the effective reproduction number. Applying the method to real-life infections, we obtained accurate estimates for the degree of age-specific immunity against monkeypox, influenza A(H5N1) and A(H7N9), and refined existing estimates of the reproduction number. Our results also suggest minimal pre-existing immunity to MERS-CoV in humans. The approach we describe can therefore provide crucial information about novel infections before serological surveys and other detailed analyses are available. The methods would also be applicable to data stratified by factors such as profession or location, which would make it possible to measure the transmission potential of emerging infections in a wide range of settings.",2015 Apr 10,"['Kucharski, Adam J.', 'Edmunds, W. John']",PLoS Comput Biol,,,True
eaf8eeee7e38b2ed41a22554d585903f14262030,PMC,Characterizing the Transmission Potential of Zoonotic Infections from Minor Outbreaks,http://dx.doi.org/10.1371/journal.pcbi.1004154,PMC4393285,25860289,CC BY,"The transmission potential of a novel infection depends on both the inherent transmissibility of a pathogen, and the level of susceptibility in the host population. However, distinguishing between these pathogen- and population-specific properties typically requires detailed serological studies, which are rarely available in the early stages of an outbreak. Using a simple transmission model that incorporates age-stratified social mixing patterns, we present a novel method for characterizing the transmission potential of subcritical infections, which have effective reproduction number R<1, from readily available data on the size of outbreaks. We show that the model can identify the extent to which outbreaks are driven by inherent pathogen transmissibility and pre-existing population immunity, and can generate unbiased estimates of the effective reproduction number. Applying the method to real-life infections, we obtained accurate estimates for the degree of age-specific immunity against monkeypox, influenza A(H5N1) and A(H7N9), and refined existing estimates of the reproduction number. Our results also suggest minimal pre-existing immunity to MERS-CoV in humans. The approach we describe can therefore provide crucial information about novel infections before serological surveys and other detailed analyses are available. The methods would also be applicable to data stratified by factors such as profession or location, which would make it possible to measure the transmission potential of emerging infections in a wide range of settings.",2015 Apr 10,"['Kucharski, Adam J.', 'Edmunds, W. John']",PLoS Comput Biol,,,False
6858a81e65c28599c9e674b9b8aa77ab11b79fad,PMC,3D Structure Prediction of Human β1-Adrenergic Receptor via Threading-Based Homology Modeling for Implications in Structure-Based Drug Designing,http://dx.doi.org/10.1371/journal.pone.0122223,PMC4393300,25860348,CC BY,"Dilated cardiomyopathy is a disease of left ventricular dysfunction accompanied by impairment of the β(1)-adrenergic receptor (β(1)-AR) signal cascade. The disturbed β(1)-AR function may be based on an elevated sympathetic tone observed in patients with heart failure. Prolonged adrenergic stimulation may induce metabolic and electrophysiological disturbances in the myocardium, resulting in tachyarrhythmia that leads to the development of heart failure in human and sudden death. Hence, β(1)-AR is considered as a promising drug target but attempts to develop effective and specific drug against this tempting pharmaceutical target is slowed down due to the lack of 3D structure of Homo sapiens β(1)-AR (hsβADR1). This study encompasses elucidation of 3D structural and physicochemical properties of hsβADR1 via threading-based homology modeling. Furthermore, the docking performance of several docking programs including Surflex-Dock, FRED, and GOLD were validated by re-docking and cross-docking experiments. GOLD and Surflex-Dock performed best in re-docking and cross docking experiments, respectively. Consequently, Surflex-Dock was used to predict the binding modes of four hsβADR1 agonists. This study provides clear understanding of hsβADR1 structure and its binding mechanism, thus help in providing the remedial solutions of cardiovascular, effective treatment of asthma and other diseases caused by malfunctioning of the target protein.",2015 Apr 10,"['Ul-Haq, Zaheer', 'Saeed, Maria', 'Halim, Sobia Ahsan', 'Khan, Waqasuddin']",PLoS One,,,True
5dee0488f20951e191da1c58d425a28eda883f49,PMC,A Bibliometric Analysis of Publications on Pluripotent Stem Cell Research,,PMC4393672,25870835,CC BY,"OBJECTIVE: Human pluripotent stem cells are self-renewing cells with the ability to differentiate into a variety of cells and are viewed to have great potential in the field of regenerative medicine. Research in pluripotent stem cells holds great promise for patient specific therapy in various diseases. In this study, pluripotent stem cell articles published from 1991 to 2012 were screened and retrieved from Science Citation Index Expanded (SCI-EXPANDED). MATERIALS AND METHODS: In this retrospective study, the publication trend, citation trends for top articles, distributions of journals and Web of Science categories were analyzed. Five bibliometric indicators including total articles, independent articles, collaborative articles, first author articles, and corresponding author articles were applied to compare publications between countries and institutions. RESULTS: The impact of top articles changed from year to year. Top cited articles in previous publication years were not the same as recent years. ""Induced pluripotent stem cell (s)"" and ""embryonic stem cell (s)"" were the most used author keywords in pluripotent stem cell research. In addition, the winner of the Nobel Prize in physiology or medicine in 2012, Prof. Shinya Yamanaka, published four of the top ten most frequently cited articles. CONCLUSION: The comprehensive analysis of highly cited articles in the stem cell field could identify milestones and important contributors, giving a historic perspective on scientific progress.",2015 Apr 8 Spring,"['Lin, Changshuan L.', 'Ho, Yuh-Shan']",Cell J,,,True
d760a0c49650a6c2a3d822bab4417057e6be1cd1,PMC,"Correction: Xie, H.; et al. 3D QSAR Studies, Pharmacophore Modeling and Virtual Screening on a Series of Steroidal Aromatase Inhibitors. Int. J. Mol. Sci. 2014, 15, 20927–20947",http://dx.doi.org/10.3390/ijms16035072,PMC4394465,25751723,CC BY,,2015 Mar 5,"['Xie, Huiding', 'Qiu, Kaixiong', 'Xie, Xiaoguang']",Int J Mol Sci,,,True
0b1af480d35b739da799df76a25463bc2ee4bbe5,PMC,The pbrB Gene Encodes a Laccase Required for DHN-Melanin Synthesis in Conidia of Talaromyces (Penicillium) marneffei,http://dx.doi.org/10.1371/journal.pone.0122728,PMC4395095,25866870,CC BY,"Talaromyces marneffei (Basionym: Penicillium marneffei) is a significant opportunistic fungal pathogen in patients infected with human immunodeficiency virus in Southeast Asia. T. marneffei cells have been shown to become melanized in vivo. Melanins are pigment biopolymers which act as a non-specific protectant against various stressors and which play an important role during virulence in fungi. The synthesis of the two most commonly found melanins in fungi, the eumelanin DOPA-melanin and the allomelanin DHN-melanin, requires the action of laccase enzymes. The T. marneffei genome encodes a number of laccases and this study describes the characterization of one of these, pbrB, during growth and development. A strain carrying a PbrB-GFP fusion shows that pbrB is expressed at high levels during asexual development (conidiation) but not in cells growing vegetatively. The pbrB gene is required for the synthesis of DHN-melanin in conidia and when deleted results in brown pigmented conidia, in contrast to the green conidia of the wild type.",2015 Apr 13,"['Sapmak, Ariya', 'Boyce, Kylie J.', 'Andrianopoulos, Alex', 'Vanittanakom, Nongnuch']",PLoS One,,,True
28f89ac0fa6a72cf3dc315817c2e670c10dec347,PMC,Hepatitis C Virus RNA Replication Depends on Specific Cis- and Trans-Acting Activities of Viral Nonstructural Proteins,http://dx.doi.org/10.1371/journal.ppat.1004817,PMC4395149,25875808,CC BY,"Many positive-strand RNA viruses encode genes that can function in trans, whereas other genes are required in cis for genome replication. The mechanisms underlying trans- and cis-preferences are not fully understood. Here, we evaluate this concept for hepatitis C virus (HCV), an important cause of chronic liver disease and member of the Flaviviridae family. HCV encodes five nonstructural (NS) genes that are required for RNA replication. To date, only two of these genes, NS4B and NS5A, have been trans-complemented, leading to suggestions that other replicase genes work only in cis. We describe a new quantitative system to measure the cis- and trans-requirements for HCV NS gene function in RNA replication and identify several lethal mutations in the NS3, NS4A, NS4B, NS5A, and NS5B genes that can be complemented in trans, alone or in combination, by expressing the NS3–5B polyprotein from a synthetic mRNA. Although NS5B RNA binding and polymerase activities can be supplied in trans, NS5B protein expression was required in cis, indicating that NS5B has a cis-acting role in replicase assembly distinct from its known enzymatic activity. Furthermore, the RNA binding and NTPase activities of the NS3 helicase domain were required in cis, suggesting that these activities play an essential role in RNA template selection. A comprehensive complementation group analysis revealed functional linkages between NS3-4A and NS4B and between NS5B and the upstream NS3–5A genes. Finally, NS5B polymerase activity segregated with a daclatasvir-sensitive NS5A activity, which could explain the synergy of this antiviral compound with nucleoside analogs in patients. Together, these studies define several new aspects of HCV replicase structure-function, help to explain the potency of HCV-specific combination therapies, and provide an experimental framework for the study of cis- and trans-acting activities in positive-strand RNA virus replication more generally.",2015 Apr 13,"['Kazakov, Teymur', 'Yang, Feng', 'Ramanathan, Harish N.', 'Kohlway, Andrew', 'Diamond, Michael S.', 'Lindenbach, Brett D.']",PLoS Pathog,,,True
13098fe624915ac71c984fbe7fe0c0a2546c66de,PMC,Hepatitis C Virus RNA Replication Depends on Specific Cis- and Trans-Acting Activities of Viral Nonstructural Proteins,http://dx.doi.org/10.1371/journal.ppat.1004817,PMC4395149,25875808,CC BY,"Many positive-strand RNA viruses encode genes that can function in trans, whereas other genes are required in cis for genome replication. The mechanisms underlying trans- and cis-preferences are not fully understood. Here, we evaluate this concept for hepatitis C virus (HCV), an important cause of chronic liver disease and member of the Flaviviridae family. HCV encodes five nonstructural (NS) genes that are required for RNA replication. To date, only two of these genes, NS4B and NS5A, have been trans-complemented, leading to suggestions that other replicase genes work only in cis. We describe a new quantitative system to measure the cis- and trans-requirements for HCV NS gene function in RNA replication and identify several lethal mutations in the NS3, NS4A, NS4B, NS5A, and NS5B genes that can be complemented in trans, alone or in combination, by expressing the NS3–5B polyprotein from a synthetic mRNA. Although NS5B RNA binding and polymerase activities can be supplied in trans, NS5B protein expression was required in cis, indicating that NS5B has a cis-acting role in replicase assembly distinct from its known enzymatic activity. Furthermore, the RNA binding and NTPase activities of the NS3 helicase domain were required in cis, suggesting that these activities play an essential role in RNA template selection. A comprehensive complementation group analysis revealed functional linkages between NS3-4A and NS4B and between NS5B and the upstream NS3–5A genes. Finally, NS5B polymerase activity segregated with a daclatasvir-sensitive NS5A activity, which could explain the synergy of this antiviral compound with nucleoside analogs in patients. Together, these studies define several new aspects of HCV replicase structure-function, help to explain the potency of HCV-specific combination therapies, and provide an experimental framework for the study of cis- and trans-acting activities in positive-strand RNA virus replication more generally.",2015 Apr 13,"['Kazakov, Teymur', 'Yang, Feng', 'Ramanathan, Harish N.', 'Kohlway, Andrew', 'Diamond, Michael S.', 'Lindenbach, Brett D.']",PLoS Pathog,,,False
61c1c4f195894c17cc2ce3caaa2d8cd617e7b892,PMC,Hepatitis C Virus RNA Replication Depends on Specific Cis- and Trans-Acting Activities of Viral Nonstructural Proteins,http://dx.doi.org/10.1371/journal.ppat.1004817,PMC4395149,25875808,CC BY,"Many positive-strand RNA viruses encode genes that can function in trans, whereas other genes are required in cis for genome replication. The mechanisms underlying trans- and cis-preferences are not fully understood. Here, we evaluate this concept for hepatitis C virus (HCV), an important cause of chronic liver disease and member of the Flaviviridae family. HCV encodes five nonstructural (NS) genes that are required for RNA replication. To date, only two of these genes, NS4B and NS5A, have been trans-complemented, leading to suggestions that other replicase genes work only in cis. We describe a new quantitative system to measure the cis- and trans-requirements for HCV NS gene function in RNA replication and identify several lethal mutations in the NS3, NS4A, NS4B, NS5A, and NS5B genes that can be complemented in trans, alone or in combination, by expressing the NS3–5B polyprotein from a synthetic mRNA. Although NS5B RNA binding and polymerase activities can be supplied in trans, NS5B protein expression was required in cis, indicating that NS5B has a cis-acting role in replicase assembly distinct from its known enzymatic activity. Furthermore, the RNA binding and NTPase activities of the NS3 helicase domain were required in cis, suggesting that these activities play an essential role in RNA template selection. A comprehensive complementation group analysis revealed functional linkages between NS3-4A and NS4B and between NS5B and the upstream NS3–5A genes. Finally, NS5B polymerase activity segregated with a daclatasvir-sensitive NS5A activity, which could explain the synergy of this antiviral compound with nucleoside analogs in patients. Together, these studies define several new aspects of HCV replicase structure-function, help to explain the potency of HCV-specific combination therapies, and provide an experimental framework for the study of cis- and trans-acting activities in positive-strand RNA virus replication more generally.",2015 Apr 13,"['Kazakov, Teymur', 'Yang, Feng', 'Ramanathan, Harish N.', 'Kohlway, Andrew', 'Diamond, Michael S.', 'Lindenbach, Brett D.']",PLoS Pathog,,,False
05e124c390d75f96fe992f78021c146b450563bf,PMC,Hepatitis C Virus RNA Replication Depends on Specific Cis- and Trans-Acting Activities of Viral Nonstructural Proteins,http://dx.doi.org/10.1371/journal.ppat.1004817,PMC4395149,25875808,CC BY,"Many positive-strand RNA viruses encode genes that can function in trans, whereas other genes are required in cis for genome replication. The mechanisms underlying trans- and cis-preferences are not fully understood. Here, we evaluate this concept for hepatitis C virus (HCV), an important cause of chronic liver disease and member of the Flaviviridae family. HCV encodes five nonstructural (NS) genes that are required for RNA replication. To date, only two of these genes, NS4B and NS5A, have been trans-complemented, leading to suggestions that other replicase genes work only in cis. We describe a new quantitative system to measure the cis- and trans-requirements for HCV NS gene function in RNA replication and identify several lethal mutations in the NS3, NS4A, NS4B, NS5A, and NS5B genes that can be complemented in trans, alone or in combination, by expressing the NS3–5B polyprotein from a synthetic mRNA. Although NS5B RNA binding and polymerase activities can be supplied in trans, NS5B protein expression was required in cis, indicating that NS5B has a cis-acting role in replicase assembly distinct from its known enzymatic activity. Furthermore, the RNA binding and NTPase activities of the NS3 helicase domain were required in cis, suggesting that these activities play an essential role in RNA template selection. A comprehensive complementation group analysis revealed functional linkages between NS3-4A and NS4B and between NS5B and the upstream NS3–5A genes. Finally, NS5B polymerase activity segregated with a daclatasvir-sensitive NS5A activity, which could explain the synergy of this antiviral compound with nucleoside analogs in patients. Together, these studies define several new aspects of HCV replicase structure-function, help to explain the potency of HCV-specific combination therapies, and provide an experimental framework for the study of cis- and trans-acting activities in positive-strand RNA virus replication more generally.",2015 Apr 13,"['Kazakov, Teymur', 'Yang, Feng', 'Ramanathan, Harish N.', 'Kohlway, Andrew', 'Diamond, Michael S.', 'Lindenbach, Brett D.']",PLoS Pathog,,,False
b70dc2c0352fbfd55b26b7d9548fad4867476948,PMC,Hepatitis C Virus RNA Replication Depends on Specific Cis- and Trans-Acting Activities of Viral Nonstructural Proteins,http://dx.doi.org/10.1371/journal.ppat.1004817,PMC4395149,25875808,CC BY,"Many positive-strand RNA viruses encode genes that can function in trans, whereas other genes are required in cis for genome replication. The mechanisms underlying trans- and cis-preferences are not fully understood. Here, we evaluate this concept for hepatitis C virus (HCV), an important cause of chronic liver disease and member of the Flaviviridae family. HCV encodes five nonstructural (NS) genes that are required for RNA replication. To date, only two of these genes, NS4B and NS5A, have been trans-complemented, leading to suggestions that other replicase genes work only in cis. We describe a new quantitative system to measure the cis- and trans-requirements for HCV NS gene function in RNA replication and identify several lethal mutations in the NS3, NS4A, NS4B, NS5A, and NS5B genes that can be complemented in trans, alone or in combination, by expressing the NS3–5B polyprotein from a synthetic mRNA. Although NS5B RNA binding and polymerase activities can be supplied in trans, NS5B protein expression was required in cis, indicating that NS5B has a cis-acting role in replicase assembly distinct from its known enzymatic activity. Furthermore, the RNA binding and NTPase activities of the NS3 helicase domain were required in cis, suggesting that these activities play an essential role in RNA template selection. A comprehensive complementation group analysis revealed functional linkages between NS3-4A and NS4B and between NS5B and the upstream NS3–5A genes. Finally, NS5B polymerase activity segregated with a daclatasvir-sensitive NS5A activity, which could explain the synergy of this antiviral compound with nucleoside analogs in patients. Together, these studies define several new aspects of HCV replicase structure-function, help to explain the potency of HCV-specific combination therapies, and provide an experimental framework for the study of cis- and trans-acting activities in positive-strand RNA virus replication more generally.",2015 Apr 13,"['Kazakov, Teymur', 'Yang, Feng', 'Ramanathan, Harish N.', 'Kohlway, Andrew', 'Diamond, Michael S.', 'Lindenbach, Brett D.']",PLoS Pathog,,,False
1951545d70e8568083cde219d2583c1aae0c4061,PMC,"Factors responsible for the emergence of arboviruses; strategies, challenges and limitations for their control",http://dx.doi.org/10.1038/emi.2015.18,PMC4395659,26038768,CC BY,"Slave trading of Africans to the Americas, during the 16th to the 19th century was responsible for the first recorded emergence in the New World of two arthropod-borne viruses (arboviruses), yellow fever virus and dengue virus. Many other arboviruses have since emerged from their sylvatic reservoirs and dispersed globally due to evolving factors that include anthropological behaviour, commercial transportation and land-remediation. Here, we outline some characteristics of these highly divergent arboviruses, including the variety of life cycles they have developed and the mechanisms by which they have adapted to evolving changes in habitat and host availability. We cite recent examples of virus emergence that exemplify how arboviruses have exploited the consequences of the modern human lifestyle. Using our current understanding of these viruses, we also attempt to demonstrate some of the limitations encountered in developing control strategies to reduce the impact of future emerging arbovirus diseases. Finally, we present recommendations for development by an international panel of experts reporting directly to World Health Organization, with the intention of providing internationally acceptable guidelines for improving emerging arbovirus disease control strategies. Success in these aims should alleviate the suffering and costs encountered during recent decades when arboviruses have emerged from their sylvatic environment.",2015 Mar 25,"['Liang, Guodong', 'Gao, Xiaoyan', 'Gould, Ernest A']",Emerg Microbes Infect,,,True
27b984da31424966ac5c45002fb7788bcf2f8a24,PMC,Cationic nanoparticles directly bind angiotensin-converting enzyme 2 and induce acute lung injury in mice,http://dx.doi.org/10.1186/s12989-015-0080-x,PMC4395934,25890286,CC BY,"BACKGROUND: Nanoparticles have become a key technology in multiple industries. However, there are growing reports of the toxicity of nanomaterials to humans. In particular, nanomaterials have been linked to lung diseases. The molecular mechanisms of nanoparticle toxicity are largely unexplored. METHODS: Acute lung injury was induced in wild-type mice and angiotensin-coverting enzyme 2 (ACE2) knockout mice by the intratracheal instillation of cationic polyamidoamine dendrimer (PAMAM) nanoparticles. For rescue experiments, losartan (15 mg/kg in PBS) was injected intraperitoneally 30 min before nanoparticle administration. RESULTS: Some PAMAM nanoparticles, but not anionic PAMAM nanoparticles or carbon nanotubes, triggered acute lung failure in mice. Mechanistically, cationic nanoparticles can directly bind ACE2, decrease its activity and down-regulate its expression level in lung tissue, resulting in deregulation of the renin-angiotensin system. Gene inactivation of Ace2 can exacerbate lung injury. Importantly, the administration of losartan, which is an angiotensin II type I receptor antagonist, can ameliorate PAMAM nanoparticle-induced lung injury. CONCLUSIONS: Our data provide molecular insight into PAMAM nanoparticle-induced lung injury and suggest potential therapeutic and screening strategies to address the safety of nanomaterials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-015-0080-x) contains supplementary material, which is available to authorized users.",2015 Mar 7,"['Sun, Yang', 'Guo, Feng', 'Zou, Zhen', 'Li, Chenggang', 'Hong, Xiaoxu', 'Zhao, Yan', 'Wang, Chenxuan', 'Wang, Hongliang', 'Liu, Haolin', 'Yang, Peng', 'Han, Zongsheng', 'Liu, Kangtai', 'Kuba, Keiji', 'Song, Bin', 'Gao, Jinming', 'Mo, Ziyao', 'Li, Dangsheng', 'Li, Bo', 'Li, Qihan', 'Zhong, Nanshan', 'Wang, Chen', 'Penninger, Josef M', 'Jiang, Chengyu']",Part Fibre Toxicol,,,False
e8b1ea3e506278ac9a195929ec4a8fb1801c4a86,PMC,Cationic nanoparticles directly bind angiotensin-converting enzyme 2 and induce acute lung injury in mice,http://dx.doi.org/10.1186/s12989-015-0080-x,PMC4395934,25890286,CC BY,"BACKGROUND: Nanoparticles have become a key technology in multiple industries. However, there are growing reports of the toxicity of nanomaterials to humans. In particular, nanomaterials have been linked to lung diseases. The molecular mechanisms of nanoparticle toxicity are largely unexplored. METHODS: Acute lung injury was induced in wild-type mice and angiotensin-coverting enzyme 2 (ACE2) knockout mice by the intratracheal instillation of cationic polyamidoamine dendrimer (PAMAM) nanoparticles. For rescue experiments, losartan (15 mg/kg in PBS) was injected intraperitoneally 30 min before nanoparticle administration. RESULTS: Some PAMAM nanoparticles, but not anionic PAMAM nanoparticles or carbon nanotubes, triggered acute lung failure in mice. Mechanistically, cationic nanoparticles can directly bind ACE2, decrease its activity and down-regulate its expression level in lung tissue, resulting in deregulation of the renin-angiotensin system. Gene inactivation of Ace2 can exacerbate lung injury. Importantly, the administration of losartan, which is an angiotensin II type I receptor antagonist, can ameliorate PAMAM nanoparticle-induced lung injury. CONCLUSIONS: Our data provide molecular insight into PAMAM nanoparticle-induced lung injury and suggest potential therapeutic and screening strategies to address the safety of nanomaterials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-015-0080-x) contains supplementary material, which is available to authorized users.",2015 Mar 7,"['Sun, Yang', 'Guo, Feng', 'Zou, Zhen', 'Li, Chenggang', 'Hong, Xiaoxu', 'Zhao, Yan', 'Wang, Chenxuan', 'Wang, Hongliang', 'Liu, Haolin', 'Yang, Peng', 'Han, Zongsheng', 'Liu, Kangtai', 'Kuba, Keiji', 'Song, Bin', 'Gao, Jinming', 'Mo, Ziyao', 'Li, Dangsheng', 'Li, Bo', 'Li, Qihan', 'Zhong, Nanshan', 'Wang, Chen', 'Penninger, Josef M', 'Jiang, Chengyu']",Part Fibre Toxicol,,,False
43c6dfd539d037ea096725addf62cad445e88959,PMC,Cationic nanoparticles directly bind angiotensin-converting enzyme 2 and induce acute lung injury in mice,http://dx.doi.org/10.1186/s12989-015-0080-x,PMC4395934,25890286,CC BY,"BACKGROUND: Nanoparticles have become a key technology in multiple industries. However, there are growing reports of the toxicity of nanomaterials to humans. In particular, nanomaterials have been linked to lung diseases. The molecular mechanisms of nanoparticle toxicity are largely unexplored. METHODS: Acute lung injury was induced in wild-type mice and angiotensin-coverting enzyme 2 (ACE2) knockout mice by the intratracheal instillation of cationic polyamidoamine dendrimer (PAMAM) nanoparticles. For rescue experiments, losartan (15 mg/kg in PBS) was injected intraperitoneally 30 min before nanoparticle administration. RESULTS: Some PAMAM nanoparticles, but not anionic PAMAM nanoparticles or carbon nanotubes, triggered acute lung failure in mice. Mechanistically, cationic nanoparticles can directly bind ACE2, decrease its activity and down-regulate its expression level in lung tissue, resulting in deregulation of the renin-angiotensin system. Gene inactivation of Ace2 can exacerbate lung injury. Importantly, the administration of losartan, which is an angiotensin II type I receptor antagonist, can ameliorate PAMAM nanoparticle-induced lung injury. CONCLUSIONS: Our data provide molecular insight into PAMAM nanoparticle-induced lung injury and suggest potential therapeutic and screening strategies to address the safety of nanomaterials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-015-0080-x) contains supplementary material, which is available to authorized users.",2015 Mar 7,"['Sun, Yang', 'Guo, Feng', 'Zou, Zhen', 'Li, Chenggang', 'Hong, Xiaoxu', 'Zhao, Yan', 'Wang, Chenxuan', 'Wang, Hongliang', 'Liu, Haolin', 'Yang, Peng', 'Han, Zongsheng', 'Liu, Kangtai', 'Kuba, Keiji', 'Song, Bin', 'Gao, Jinming', 'Mo, Ziyao', 'Li, Dangsheng', 'Li, Bo', 'Li, Qihan', 'Zhong, Nanshan', 'Wang, Chen', 'Penninger, Josef M', 'Jiang, Chengyu']",Part Fibre Toxicol,,,False
fd60728329125d9577016c256ad2bcd69240ac21,PMC,Cationic nanoparticles directly bind angiotensin-converting enzyme 2 and induce acute lung injury in mice,http://dx.doi.org/10.1186/s12989-015-0080-x,PMC4395934,25890286,CC BY,"BACKGROUND: Nanoparticles have become a key technology in multiple industries. However, there are growing reports of the toxicity of nanomaterials to humans. In particular, nanomaterials have been linked to lung diseases. The molecular mechanisms of nanoparticle toxicity are largely unexplored. METHODS: Acute lung injury was induced in wild-type mice and angiotensin-coverting enzyme 2 (ACE2) knockout mice by the intratracheal instillation of cationic polyamidoamine dendrimer (PAMAM) nanoparticles. For rescue experiments, losartan (15 mg/kg in PBS) was injected intraperitoneally 30 min before nanoparticle administration. RESULTS: Some PAMAM nanoparticles, but not anionic PAMAM nanoparticles or carbon nanotubes, triggered acute lung failure in mice. Mechanistically, cationic nanoparticles can directly bind ACE2, decrease its activity and down-regulate its expression level in lung tissue, resulting in deregulation of the renin-angiotensin system. Gene inactivation of Ace2 can exacerbate lung injury. Importantly, the administration of losartan, which is an angiotensin II type I receptor antagonist, can ameliorate PAMAM nanoparticle-induced lung injury. CONCLUSIONS: Our data provide molecular insight into PAMAM nanoparticle-induced lung injury and suggest potential therapeutic and screening strategies to address the safety of nanomaterials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-015-0080-x) contains supplementary material, which is available to authorized users.",2015 Mar 7,"['Sun, Yang', 'Guo, Feng', 'Zou, Zhen', 'Li, Chenggang', 'Hong, Xiaoxu', 'Zhao, Yan', 'Wang, Chenxuan', 'Wang, Hongliang', 'Liu, Haolin', 'Yang, Peng', 'Han, Zongsheng', 'Liu, Kangtai', 'Kuba, Keiji', 'Song, Bin', 'Gao, Jinming', 'Mo, Ziyao', 'Li, Dangsheng', 'Li, Bo', 'Li, Qihan', 'Zhong, Nanshan', 'Wang, Chen', 'Penninger, Josef M', 'Jiang, Chengyu']",Part Fibre Toxicol,,,False
1b42f78eee63e2f5c5a58a59759dc119ef1f73da,PMC,Cationic nanoparticles directly bind angiotensin-converting enzyme 2 and induce acute lung injury in mice,http://dx.doi.org/10.1186/s12989-015-0080-x,PMC4395934,25890286,CC BY,"BACKGROUND: Nanoparticles have become a key technology in multiple industries. However, there are growing reports of the toxicity of nanomaterials to humans. In particular, nanomaterials have been linked to lung diseases. The molecular mechanisms of nanoparticle toxicity are largely unexplored. METHODS: Acute lung injury was induced in wild-type mice and angiotensin-coverting enzyme 2 (ACE2) knockout mice by the intratracheal instillation of cationic polyamidoamine dendrimer (PAMAM) nanoparticles. For rescue experiments, losartan (15 mg/kg in PBS) was injected intraperitoneally 30 min before nanoparticle administration. RESULTS: Some PAMAM nanoparticles, but not anionic PAMAM nanoparticles or carbon nanotubes, triggered acute lung failure in mice. Mechanistically, cationic nanoparticles can directly bind ACE2, decrease its activity and down-regulate its expression level in lung tissue, resulting in deregulation of the renin-angiotensin system. Gene inactivation of Ace2 can exacerbate lung injury. Importantly, the administration of losartan, which is an angiotensin II type I receptor antagonist, can ameliorate PAMAM nanoparticle-induced lung injury. CONCLUSIONS: Our data provide molecular insight into PAMAM nanoparticle-induced lung injury and suggest potential therapeutic and screening strategies to address the safety of nanomaterials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-015-0080-x) contains supplementary material, which is available to authorized users.",2015 Mar 7,"['Sun, Yang', 'Guo, Feng', 'Zou, Zhen', 'Li, Chenggang', 'Hong, Xiaoxu', 'Zhao, Yan', 'Wang, Chenxuan', 'Wang, Hongliang', 'Liu, Haolin', 'Yang, Peng', 'Han, Zongsheng', 'Liu, Kangtai', 'Kuba, Keiji', 'Song, Bin', 'Gao, Jinming', 'Mo, Ziyao', 'Li, Dangsheng', 'Li, Bo', 'Li, Qihan', 'Zhong, Nanshan', 'Wang, Chen', 'Penninger, Josef M', 'Jiang, Chengyu']",Part Fibre Toxicol,,,True
424d6c622643d36a7f8d9a1d2714f4cef49387ed,PMC,"1,2,3,4,6-Penta-O-galloylglucose within Galla Chinensis Inhibits Human LDH-A and Attenuates Cell Proliferation in MDA-MB-231 Breast Cancer Cells",http://dx.doi.org/10.1155/2015/276946,PMC4396556,25918543,CC BY,"A characteristic feature of aggressive malignancy is the overexpression of lactic acid dehydrogenase- (LDH-) A, concomitant to pericellular accumulation of lactate. In a recent high-throughput screening, we identified Rhus chinensis (Mill.) gallnut (RCG) (also known as Galla Chinensis) extract as a potent (IC(50) < 1 µg/mL) inhibitor of human LDH-A (hLDH-A). In this study, through bioactivity guided fractionation of the crude extract, the data demonstrate that penta-1,2,3,4,6-O-galloyl-β-D-glucose (PGG) was a primary constituent responsible for hLDH-A inhibition, present at ~9.95 ± 0.34% dry weight. Theoretical molecular docking studies of hLDH-A indicate that PGG acts through competitive binding at the NADH cofactor site, effects confirmed by functional enzyme studies where the IC(50) = 27.32 nM was reversed with increasing concentration of NADH. Moreover, we confirm protein expression of hLDH-A in MDA-231 human breast carcinoma cells and show that PGG was toxic (LC(50) = 94.18 µM), parallel to attenuated lactic acid production (IC(50) = 97.81 µM). In a 72-hour cell proliferation assay, PGG was found to be a potent cytostatic agent with ability to halt cell division (IC(50) = 1.2 µM) relative to paclitaxel (IC(50) < 100 nM). In summary, these findings demonstrate that PGG is a potent hLDH-A inhibitor with significant capacity to halt proliferation of human breast cancer cells.",2015 Mar 30,"['Deiab, Shihab', 'Mazzio, Elizabeth', 'Eyunni, Suresh', 'McTier, Oshlii', 'Mateeva, Nelly', 'Elshami, Faisel', 'Soliman, Karam F. A.']",Evid Based Complement Alternat Med,,,True
eaaa5939391fb99e06e8d6b8723e6b061632b1c3,PMC,Selection of key recommendations for quality indicators describing good quality outbreak response,http://dx.doi.org/10.1186/s12879-015-0896-x,PMC4397715,25888491,CC BY,"BACKGROUND: The performance of recommended control measures is necessary for quick and uniform infectious disease outbreak control. To assess whether these procedures are performed, a valid set of quality indicators (QIs) is required. The goal of this study was to select a set of key recommendations that can be systematically translated into QIs to measure the quality of infectious disease outbreak response from the perspective of disaster emergency responders and infectious disease control professionals. METHODS: Applying the Rand modified Delphi procedure, the following steps were taken to systematically select a set of key recommendations: extraction of recommendations from relevant literature; appraisal of the recommendations in terms of relevance through questionnaires to experts; expert meeting to discuss recommendations; prioritization of recommendations through a second questionnaire; and final expert meeting to approve the selected set. Infectious disease physicians and nurses, policymakers and communication experts participated in the expert group (n = 48). RESULTS: In total, 54 national and international publications were systematically searched for recommendations, yielding over 200 recommendations. The Rand modified Delphi procedure resulted in a set of 65 key recommendations. The key recommendations were categorized into 10 domains describing the whole response pathway from outbreak recognition to aftercare. CONCLUSION: This study provides a set of key recommendations that represents ‘good quality of response to an infectious disease outbreak’. These key recommendations can be systematically translated into QIs. Organizations and professionals involved in outbreak control can use these QIs to monitor the quality of response to infectious disease outbreaks and to assess in which domains improvement is needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0896-x) contains supplementary material, which is available to authorized users.",2015 Mar 31,"['Belfroid, Evelien', 'LA Hautvast, Jeannine', 'Hilbink, Mirrian', 'Timen, Aura', 'Hulscher, Marlies EJL']",BMC Infect Dis,,,True
8a665903721dadcf01c1dd7476a7715709cee0ad,PMC,Outcomes of Early Administration of Cidofovir in Non-Immunocompromised Patients with Severe Adenovirus Pneumonia,http://dx.doi.org/10.1371/journal.pone.0122642,PMC4398328,25875735,CC BY,"The benefits of treatment with antiviral therapy for severe adenovirus (AdV) pneumonia are not well established. We described the clinical characteristics and treatment outcomes of early cidofovir treatment of severe AdV pneumonia in non-immunocompromised patients. We retrospectively reviewed the medical records of all patients diagnosed with severe AdV pneumonia between 2012 and 2014. A total of seven non-immunocompromised patients with severe AdV pneumonia were identified, and all isolates typed (n = 6) were human AdV-B55. All patients had progressive respiratory failure with lobar consolidation with or without patchy ground glass opacity. Three patients required vasopressors and mechanical ventilation. All patients had abnormal laboratory findings including: leukopenia, thrombocytopenia, or elevated liver enzymes. After admission, all patients received antiviral therapy with cidofovir, and the median time from admission to cidofovir administration was 48 h and median the time from onset of symptoms to cidofovir administration was 7.1 days. After cidofovir administration, complete symptomatic improvement occurred after a median of 12 days and radiographic resolution occurred after a median of 21 days. Consequently, all patients completely improved without complications. Our data suggest that early administration of cidofovir in the course of treatment for respiratory failure as a result of AdV pneumonia in non-immunocompromised patients could be a treatment strategy worth considering, especially in cases of HAdV-55 infection.",2015 Apr 15,"['Kim, Se Jin', 'Kim, Kang', 'Park, Sung Bum', 'Hong, Duck Jin', 'Jhun, Byung Woo']",PLoS One,,,True
fed1fd6ad6a0fff6d3532a8b13f12f25347928b7,PMC,Social Capital and Health-Protective Behavior Intentions in an Influenza Pandemic,http://dx.doi.org/10.1371/journal.pone.0122970,PMC4398366,25874625,CC BY,"Health-protective behaviors, such as receiving a vaccine, wearing a face mask, and washing hands frequently, can reduce the risk of contracting influenza. However, little is known about how social capital may influence health-protective behavior in the general population. This study examined whether each of the social capital dimensions (bonding, bridging, and linking) contributed to the intention to adopt any of the health-protective behaviors in an influenza pandemic. The data of this study were from the 2014 Taiwan Social Change Survey. A stratified, three-stage probability proportional-to-size sampling from across the nation, was conducted to select adults aged 20 years and older (N = 1,745). Bonding social capital was measured by the frequency of neighborly contact and support. Bridging social capital was measured based on association membership. Linking social capital was measured according to general government trust and trust in the government’s capacity to counter an influenza pandemic. Binary logistic regressions were used to assess the multivariate associations between social capital and behavioral intention. The study results indicate that social capital may influence the response to influenza pandemic. Specifically, the intention to receive a vaccine and to wash hands more frequently were associated with the linking dimension and the bonding dimension of social capital, while the intention to wear a face mask was associated with all forms of social capital. The findings of this study suggest that government credibility and interpersonal networks may play a crucial role in health-protective behavior. This study provides new insights into how to improve the effectiveness of influenza prevention campaigns.",2015 Apr 15,"['Chuang, Ying-Chih', 'Huang, Ya-Li', 'Tseng, Kuo-Chien', 'Yen, Chia-Hsin', 'Yang, Lin-hui']",PLoS One,,,True
886c69ba9b7fb6441b3dc9c06d77abf30e3a0703,PMC,The UPR Branch IRE1-bZIP60 in Plants Plays an Essential Role in Viral Infection and Is Complementary to the Only UPR Pathway in Yeast,http://dx.doi.org/10.1371/journal.pgen.1005164,PMC4398384,25875739,CC BY,"The unfolded protein response (UPR) signaling network encompasses two pathways in plants, one mediated by inositol-requiring protein-1 (IRE1)-bZIP60 mRNA and the other by site-1/site-2 proteases (S1P/S2P)-bZIP17/bZIP28. As the major sensor of UPR in eukaryotes, IRE1, in response to endoplasmic reticulum (ER) stress, catalyzes the unconventional splicing of HAC1 in yeast, bZIP60 in plants and XBP1 in metazoans. Recent studies suggest that IRE1p and HAC1 mRNA, the only UPR pathway found in yeast, evolves as a cognate system responsible for the robust UPR induction. However, the functional connectivity of IRE1 and its splicing target in multicellular eukaryotes as well as the degree of conservation of IRE1 downstream signaling effectors across eukaryotes remains to be established. Here, we report that IRE1 and its substrate bZIP60 function as a strictly cognate enzyme-substrate pair to control viral pathogenesis in plants. Moreover, we show that the S1P/S2P-bZIP17/bZIP28 pathway, the other known branch of UPR in plants, does not play a detectable role in virus infection, demonstrating the distinct function of the IRE1-bZIP60 pathway in plants. Furthermore, we provide evidence that bZIP60 and HAC1, products of the enzyme-substrate duet, rather than IRE1, are functionally replaceable to cope with ER stress in yeast. Taken together, we conclude that the downstream signaling of the IRE1-mediated splicing is evolutionarily conserved in yeast and plants, and that the IRE1-bZIP60 UPR pathway not only confers overlapping functions with the other UPR branch in fundamental biology but also may exert a unique role in certain biological processes such as virus-plant interactions.",2015 Apr 15,"['Zhang, Lingrui', 'Chen, Hui', 'Brandizzi, Federica', 'Verchot, Jeanmarie', 'Wang, Aiming']",PLoS Genet,,,True
ad00ba859cb901a728e33191c4795084743cb986,PMC,"Early Detection for Cases of Enterovirus- and Influenza-Like Illness through a Newly Established School-Based Syndromic Surveillance System in Taipei, January 2010 ~ August 2011",http://dx.doi.org/10.1371/journal.pone.0122865,PMC4398411,25875080,CC BY,"School children may transmit pathogens with cluster cases occurring on campuses and in families. In response to the 2009 influenza A (H1N1) pandemic, Taipei City Government officials developed a School-based Infectious Disease Syndromic Surveillance System (SID-SSS). Teachers and nurses from preschools to universities in all 12 districts within Taipei are required to daily report cases of symptomatic children or sick leave requests through the SID-SSS. The pre-diagnosis at schools is submitted firstly as common pediatric disease syndrome-groups and re-submitted after confirmation by physicians. We retrieved these data from January 2010 to August 2011 for spatio-temporal analysis and evaluated the temporal trends with cases obtained from both the Emergency Department-based Syndromic Surveillance System (ED-SSS) and the Longitudinal Health Insurance Database 2005 (LHID2005). Through the SID-SSS, enterovirus-like illness (EVI) and influenza-like illness (ILI) were the two most reported syndrome groups (77.6% and 15.8% among a total of 19,334 cases, respectively). The pre-diagnosis judgments made by school teachers and nurses showed high consistency with physicians’ clinical diagnoses for EVI (97.8%) and ILI (98.9%). Most importantly, the SID-SSS had better timeliness with earlier peaks of EVI and ILI than those in the ED-SSS. Furthermore, both of the syndrome groups in these two surveillance systems had the best correlation reaching 0.98 and 0.95, respectively (p<0.01). Spatio-temporal analysis observed the patterns of EVI and ILI both diffuse from the northern suburban districts to central Taipei, with ILI spreading faster. This novel system can identify early suspected cases of two important pediatric infections occurring at schools, and clusters from schools/families. It was also cost-effective (95.5% of the operation cost reduced and 59.7% processing time saved). The timely surveillance of mild EVI and ILI cases integrated with spatial analysis may help public health decision-makers with where to target for enhancing surveillance and prevention measures to minimize severe cases.",2015 Apr 15,"['Weng, Ting Chia', 'Chan, Ta Chien', 'Lin, Hsien Tang', 'Chang, Chia Kun Jasper', 'Wang, Wen Wen', 'Li, Zheng Rong Tiger', 'Cheng, Hao-Yuan', 'Chu, Yu-Roo', 'Chiu, Allen Wen-Hsiang', 'Yen, Muh-Yong', 'King, Chwan-Chuen']",PLoS One,,,True
06989a9659f1b9b10abc5b92a90ecff38a778d55,PMC,Identification of a Novel Afipia Species Isolated from an Indian Flying Fox,http://dx.doi.org/10.1371/journal.pone.0121274,PMC4398416,25874801,CC BY,"An old world fruit bat Pteropus giganteus, held in captivity and suffering from necrosis of its wing digits, failed to respond to antibiotic therapy and succumbed to the infection. Samples submitted to the National Centre for Foreign Animal Disease were tested for viral infection. Vero E6 cells exhibited minor but unique cytopathic effects on second blind passage, and full CPE by passage four. Utilizing an unbiased random amplification technique from cell culture supernatant, we identified a bacterium belonging to the Bradyrhizobiaceae. Purification of cell culture supernatant on TY media revealed a slow growing bacterial isolate. In this study using electron microscopy, 16S rRNA gene analysis and whole genome sequencing, we identify a novel bacterial species associated with the site of infection belonging to the genus Afipia. This genus of bacteria is very diverse, with only a limited number of species characterized. Afipia felis, previously described as the etiological agent to cause cat scratch disease, and Afipia septicemium, most recently shown to cause disease in humans, highlight the potential for members of this genus to form a branch of opportunistic pathogens within the Bradyrhizobiaceae. Increased utilization of next generation sequencing and genomics will aid in classifying additional members of this intriguing bacterial genera.",2015 Apr 15,"['Pickering, Brad S.', 'Tyler, Shaun', 'Smith, Greg', 'Burton, Lynn', 'Li, Mingyi', 'Dallaire, André', 'Weingartl, Hana']",PLoS One,,,True
9a14d4a0dbda0e0ece8cca513fc9841b6cb1b2d7,PMC,Identification of a Novel Afipia Species Isolated from an Indian Flying Fox,http://dx.doi.org/10.1371/journal.pone.0121274,PMC4398416,25874801,CC BY,"An old world fruit bat Pteropus giganteus, held in captivity and suffering from necrosis of its wing digits, failed to respond to antibiotic therapy and succumbed to the infection. Samples submitted to the National Centre for Foreign Animal Disease were tested for viral infection. Vero E6 cells exhibited minor but unique cytopathic effects on second blind passage, and full CPE by passage four. Utilizing an unbiased random amplification technique from cell culture supernatant, we identified a bacterium belonging to the Bradyrhizobiaceae. Purification of cell culture supernatant on TY media revealed a slow growing bacterial isolate. In this study using electron microscopy, 16S rRNA gene analysis and whole genome sequencing, we identify a novel bacterial species associated with the site of infection belonging to the genus Afipia. This genus of bacteria is very diverse, with only a limited number of species characterized. Afipia felis, previously described as the etiological agent to cause cat scratch disease, and Afipia septicemium, most recently shown to cause disease in humans, highlight the potential for members of this genus to form a branch of opportunistic pathogens within the Bradyrhizobiaceae. Increased utilization of next generation sequencing and genomics will aid in classifying additional members of this intriguing bacterial genera.",2015 Apr 15,"['Pickering, Brad S.', 'Tyler, Shaun', 'Smith, Greg', 'Burton, Lynn', 'Li, Mingyi', 'Dallaire, André', 'Weingartl, Hana']",PLoS One,,,False
5013cc7e09951e93e65dd4b13b0af846a35cab97,PMC,Identification of a Novel Afipia Species Isolated from an Indian Flying Fox,http://dx.doi.org/10.1371/journal.pone.0121274,PMC4398416,25874801,CC BY,"An old world fruit bat Pteropus giganteus, held in captivity and suffering from necrosis of its wing digits, failed to respond to antibiotic therapy and succumbed to the infection. Samples submitted to the National Centre for Foreign Animal Disease were tested for viral infection. Vero E6 cells exhibited minor but unique cytopathic effects on second blind passage, and full CPE by passage four. Utilizing an unbiased random amplification technique from cell culture supernatant, we identified a bacterium belonging to the Bradyrhizobiaceae. Purification of cell culture supernatant on TY media revealed a slow growing bacterial isolate. In this study using electron microscopy, 16S rRNA gene analysis and whole genome sequencing, we identify a novel bacterial species associated with the site of infection belonging to the genus Afipia. This genus of bacteria is very diverse, with only a limited number of species characterized. Afipia felis, previously described as the etiological agent to cause cat scratch disease, and Afipia septicemium, most recently shown to cause disease in humans, highlight the potential for members of this genus to form a branch of opportunistic pathogens within the Bradyrhizobiaceae. Increased utilization of next generation sequencing and genomics will aid in classifying additional members of this intriguing bacterial genera.",2015 Apr 15,"['Pickering, Brad S.', 'Tyler, Shaun', 'Smith, Greg', 'Burton, Lynn', 'Li, Mingyi', 'Dallaire, André', 'Weingartl, Hana']",PLoS One,,,False
e62f6de9bc9588f663d52ae7d998bbe160485d48,PMC,Association of low serum TGF-β level in hantavirus infected patients with severe disease,http://dx.doi.org/10.1186/s12865-015-0085-0,PMC4399110,25888018,CC BY,"BACKGROUND: Hantaviruses are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome, an immune-mediated pathogenesis is discussed. The aim of the present study was to investigate the role of TGF-β expression in acute hantavirus infection. RESULTS: We retrospectively studied 77 patients hospitalised with acute Puumala infection during a hantavirus epidemic in Germany in 2012. Hantavirus infection was confirmed by positive anti-Puumala hantavirus IgG and IgM. Plasma levels of transforming growth factor (TGF)-β1 and TGF-β2 were analysed. Based on glomerular filtration rate on admission, patients were divided in mild and severe course of disease. Puumala virus RNA was detected by PCR amplification of the viral L segment gene. Out of 77 Puumala virus infected patients, 52 (68%) were male. A seasonal distribution was detected in our cohort with a peak in summer 2012, the highest incidence was observed in the age group of 30–39 years. Puumala virus RNA was detectable in 4/77 cases. Patients with severe disease had a significant longer hospital stay than patients with mild disease (6.2 vs 3.6 days). Thrombocyte count (186 vs 225 per nl), serum TGF-β1 (74 vs 118 ng/l) and TGF-β2 (479 vs 586 pg/l) were significantly lower in severe compared to mild disease. However, C-reactive protein (CRP) was significantly higher in patients with severe disease (62 vs 40 mg/l). TGF-β1/Cr was the most sensitive and specific marker associated with renal dysfunction. CONCLUSION: High serum CRP and low serum TGF-β in the early phase of hantavirus infection is associated with a severe course of disease. Our results support the hypothesis of an immune-mediated pathogenesis in hantavirus infection.",2015 Apr 14,"['Sadeghi, Mahmoud', 'Lahdou, Imad', 'Ettinger, Jakob', 'Navid, Mojdeh Heidary', 'Daniel, Volker', 'Zeier, Martin', 'Hofmann, Jörg', 'Opelz, Gerhard', 'Schnitzler, Paul']",BMC Immunol,,,True
9e7a93b167e9c3ffc970caf4a644d63439410cc5,PMC,Impact of MBL and MASP-2 gene polymorphism and its interaction on susceptibility to tuberculosis,http://dx.doi.org/10.1186/s12879-015-0879-y,PMC4399571,25887173,CC BY,"BACKGROUND: Mannose-binding lectin (MBL) and MBL-associated serine proteases 2 (MASP-2) are important proteins in the lectin pathway of the immune system. Polymorphism of MBL and MASP-2 genes may affect the serum concentration of MBL and MASP-2. This study explores the association between MBL and MASP-2 gene polymorphism and their interactions and the susceptibility to tuberculosis (TB). METHOD: A total of 503 patients with TB and 419 healthy controls were recruited to participate in this case-control study. PCR-SSP technology was applied to genotype rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes. Demographic data and some exposure information were also obtained from study participants. Unconditional logistic regression analysis was used to identify association between the various factors and TB whilst Marginal Structural Linear Odds Models were used to estimate the interactions. RESULTS: Both genotype GC at rs7096206 of MBL genes and genotype TC at rs2273346 and rs6695096 of MASP-2 genes were more prevalent in the TB patient group than the healthy control group (P < 0.05, OR 1.393, 1.302 and 1.426 respectively). The relative excess risk of interaction (RERI) between rs7096206 of MBL genes and rs2273346 and rs6695096 of MASP-2 genes was 0.897 (95% CI: 0.282, 1.513) and 1.142 (95% CI: 0.755, 1.530) respectively (P < 0.05). CONCLUSION: Polymorphisms of MBL (rs7096206) and MASP-2 (rs2273346 and rs6695096) were associated with the susceptibility of TB, and there were gene-gene interactions among them.",2015 Mar 25,"['Chen, Mengshi', 'Liang, Ying', 'Li, Wufei', 'Wang, Mian', 'Hu, Li', 'Abuaku, Benjamin Kwaku', 'Huang, Xin', 'Tan, Hongzhuan', 'Wen, Shi Wu']",BMC Infect Dis,,,True
035f1d6b6c461d045fd19d69e4e9c1de221f4a0d,PMC,Synthetic lethals in HIV: ways to avoid drug resistance: Running title: Preventing HIV resistance,http://dx.doi.org/10.1186/s13062-015-0044-y,PMC4399722,25888435,CC BY,"BACKGROUND: RNA viruses rapidly accumulate genetic variation, which can give rise to synthetic lethal (SL) and deleterious (SD) mutations. Synthetic lethal mutations (non-lethal when alone but lethal when combined in one genome) have been studied to develop cancer therapies. This principle can also be used against fast-evolving RNA-viruses. Indeed, targeting protein sites involved in SD + SL interactions with a drug would render any mutation of such sites, lethal. RESULTS: Here, we set up a strategy to detect intragenic pairs of SL and SD at the surface of the protein to predict less escapable drug target sites. For this, we detected SD + SL, studying HIV protease (PR) and reverse transcriptase (RT) sequence alignments from two groups of VIH(+) individuals: treated with drugs (T) or not (NT). Using a series of statistical approaches, we were able to propose bona fide SD + SL couples. When focusing on spatially close co-variant SD + SL couples at the surface of the protein, we found 5 SD + SL groups (2 in the protease and 3 in the reverse transcriptase), which could be good candidates to form pockets to accommodate potential drugs. CONCLUSIONS: Thus, designing drugs targeting these specific SD + SL groups would not allow the virus to mutate any residue involved in such groups without losing an essential function. Moreover, we also show that the selection pressure induced by the treatment leads to the appearance of new mutations, which change the mutational landscape of the protein. This drives the existence of differential SD + SL couples between the drug-treated and non-treated groups. Thus, new anti-viral drugs should be designed differently to target such groups. REVIEWERS: This article was reviewed by Neil Greenspan Csaba Pal and István Simon. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13062-015-0044-y) contains supplementary material, which is available to authorized users.",2015 Apr 17,"['Petitjean, Michel', 'Badel, Anne', 'Veitia, Reiner A', 'Vanet, Anne']",Biol Direct,,,True
774e74e60cb62c3057145f6b98501fe532acdbdd,PMC,Development and Application of an ELISA for the Detection of Porcine Deltacoronavirus IgG Antibodies,http://dx.doi.org/10.1371/journal.pone.0124363,PMC4399883,25881086,CC BY,"Porcine deltacoronavirus (PDCoV), also known as porcine coronavirus HKU15, was first detected in North America in early 2014 and associated with enteric disease in pigs, resulting in an urgent need to further investigate the ecology of this virus. While assays detecting nucleic acids were implemented quickly, assays to detect anti-PDCoV antibodies have not been available. In this study, an indirect anti-PDCoV IgG enzyme-linked immunosorbent assay (ELISA) based on the putative S1 portion of the spike protein was developed and utilized to determine the prevalence of anti-PDCoV IgG in U.S. pigs. The diagnostic sensitivity of the PDCoV ELISA was 91% with a diagnostic specificity of 95%. A total of 968 serum samples were tested including samples with confirmed infection with PDCoV, porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus or porcine respiratory coronavirus. There was no cross-reactivity with any of the other coronaviruses. Among 355 arbitrarily selected serum samples collected in 2014 and originating from 51 farms across 18 U.S. states, anti-PDCoV IgG antibodies were detected in 8.7% of the samples and in 25.5% of the farms whereas anti-PEDV IgG was detected in 22.8% of the samples and in 54.9% of the farms. In addition, anti-PDCoV IgG antibodies were detected in archived samples collected in 2010, perhaps indicating an earlier undetected introduction into the U.S. pig population. Overall, the obtained data suggest that PDCoV seroprevalence in U.S. pigs is lower compared to PEDV and PDCoV may have been introduced to the U.S. prior to PEDV.",2015 Apr 16,"['Thachil, Anil', 'Gerber, Priscilla F.', 'Xiao, Chao-Ting', 'Huang, Yao-Wei', 'Opriessnig, Tanja']",PLoS One,,,True
220fbe1f5e79e25737c0624de9a4245bfee48ec0,PMC,Complete genome sequence of canine astrovirus with molecular and epidemiological characterisation of UK strains,http://dx.doi.org/10.1016/j.vetmic.2015.03.011,PMC4401448,25818578,CC BY,"Astroviruses are a common cause of gastroenteritis in children worldwide. These viruses can also cause infection in a range of domestic and wild animal species. Canine astrovirus (CaAstV) was first identified in the USA, and has since been reported in dogs from Europe, the Far East and South America. We sought to determine whether CaAstV is circulating in the UK dog population, and to characterise any identified strains. Stool samples were collected from pet dogs in the UK with and without gastroenteritis, and samples were screened for CaAstV by qPCR. Four CaAstV positive samples were identified from dogs with gastroenteritis (4/67, 6.0%), whereas no samples from healthy dogs were positive (p < 0.001). Sequencing of the capsid sequences from the four CaAstV strains found significant genetic heterogeneity, with only 80% amino acid identity between strains. The full genome sequence of two UK CaAstV strains was then determined, confirming that CaAstV conforms to the classic genome organisation of other astroviruses with ORF1a and ORF1b separated by a frameshift and ORF2 encoding the capsid protein. This is the first report describing the circulation of CaAstV in UK dogs with clinical signs of gastroenteritis, and the first description of the full-length genomes of two CaAstV strains.",2015 May 15,"['Caddy, Sarah L.', 'Goodfellow, Ian']",Vet Microbiol,,,False
95ab4b0ddc015a430ed865c9cdd105f1e50faf31,PMC,Phase 1 Study of Pandemic H1 DNA Vaccine in Healthy Adults,http://dx.doi.org/10.1371/journal.pone.0123969,PMC4401709,25884189,CC0,"BACKGROUND: A novel, swine-origin influenza A (H1N1) virus was detected worldwide in April 2009, and the World Health Organization (WHO) declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1) influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1) licensed monovalent inactivated vaccine (MIV). METHODS: 20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector) at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3–17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry. RESULTS: Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine. CONCLUSIONS: H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics. TRIAL REGISTRATION: Clinicaltrials.gov NCT00973895",2015 Apr 17,"['Crank, Michelle C.', 'Gordon, Ingelise J.', 'Yamshchikov, Galina V.', 'Sitar, Sandra', 'Hu, Zonghui', 'Enama, Mary E.', 'Holman, LaSonji A.', 'Bailer, Robert T.', 'Pearce, Melissa B.', 'Koup, Richard A.', 'Mascola, John R.', 'Nabel, Gary J.', 'Tumpey, Terrence M.', 'Schwartz, Richard M.', 'Graham, Barney S.', 'Ledgerwood, Julie E.', None]",PLoS One,,,True
27ada359a2b9536a180bd93585f47a13d5b82517,PMC,Phase 1 Study of Pandemic H1 DNA Vaccine in Healthy Adults,http://dx.doi.org/10.1371/journal.pone.0123969,PMC4401709,25884189,CC0,"BACKGROUND: A novel, swine-origin influenza A (H1N1) virus was detected worldwide in April 2009, and the World Health Organization (WHO) declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1) influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1) licensed monovalent inactivated vaccine (MIV). METHODS: 20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector) at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3–17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry. RESULTS: Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine. CONCLUSIONS: H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics. TRIAL REGISTRATION: Clinicaltrials.gov NCT00973895",2015 Apr 17,"['Crank, Michelle C.', 'Gordon, Ingelise J.', 'Yamshchikov, Galina V.', 'Sitar, Sandra', 'Hu, Zonghui', 'Enama, Mary E.', 'Holman, LaSonji A.', 'Bailer, Robert T.', 'Pearce, Melissa B.', 'Koup, Richard A.', 'Mascola, John R.', 'Nabel, Gary J.', 'Tumpey, Terrence M.', 'Schwartz, Richard M.', 'Graham, Barney S.', 'Ledgerwood, Julie E.', None]",PLoS One,,,True
0ca8648d40bee3056b3f9840de6d34b57ed121d0,PMC,Infectious Bursal Disease Virus VP5 Polypeptide: A Phosphoinositide-Binding Protein Required for Efficient Cell-to-Cell Virus Dissemination,http://dx.doi.org/10.1371/journal.pone.0123470,PMC4401730,25886023,CC BY,"Infectious bursal disease virus (IBDV), a member of the Birnaviridae family, is a major avian pathogen responsible for an immunosuppressive disease affecting juvenile chickens. The IBDV genome is formed by two dsRNA segments. The largest one harbors two partially overlapping open reading frames encoding a non-structural polypeptide, known as VP5, and a large polyprotein, respectively. VP5 is non-essential for virus replication. However, it plays a major role in IBDV pathogenesis. VP5 accumulates at the plasma membrane (PM) of IBDV-infected cells. We have analyzed the mechanism underlying the VP5 PM targeting. Updated topological prediction algorithm servers fail to identify a transmembrane domain within the VP5 sequence. However, the VP5 polycationic C-terminal region, harboring three closely spaced patches formed by two or three consecutive basic amino acid residues (lysine or arginine), might account for its PM tropism. We have found that mutations, either C-terminal VP5 deletions or replacement of basic amino acids by alanine residues, that reduce the electropositive charge of the VP5 C-terminus abolish PM targeting. Lipid overlay assays performed with an affinity-purified Flag-tagged VP5 (FVP5) protein version show that this polypeptide binds several phosphoinositides (PIP), exhibiting a clear preference for monophosphate species. Experiments performed with FVP5 mutant proteins lacking the polycationic domain demonstrate that this region is essential for PIP binding. Data gathered with IBDV mutants expressing C-terminal deleted VP5 polypeptides generated by reverse genetics demonstrate that the VP5-PIP binding domain is required both for its PM targeting in infected cells, and for efficient virus dissemination. Data presented here lead us to hypothesize that IBDV might use a non-lytic VP5-dependent cell-to-cell spreading mechanism.",2015 Apr 17,"['Méndez, Fernando', 'de Garay, Tomás', 'Rodríguez, Dolores', 'Rodríguez, José F.']",PLoS One,,,True
8f11a3876dfbf3ba4a143b9e2ad122b8c2b9c2be,PMC,An ensemble strategy that significantly improves de novo assembly of microbial genomes from metagenomic next-generation sequencing data,http://dx.doi.org/10.1093/nar/gkv002,PMC4402509,25586223,CC BY,"Next-generation sequencing (NGS) approaches rapidly produce millions to billions of short reads, which allow pathogen detection and discovery in human clinical, animal and environmental samples. A major limitation of sequence homology-based identification for highly divergent microorganisms is the short length of reads generated by most highly parallel sequencing technologies. Short reads require a high level of sequence similarities to annotated genes to confidently predict gene function or homology. Such recognition of highly divergent homologues can be improved by reference-free (de novo) assembly of short overlapping sequence reads into larger contigs. We describe an ensemble strategy that integrates the sequential use of various de Bruijn graph and overlap-layout-consensus assemblers with a novel partitioned sub-assembly approach. We also proposed new quality metrics that are suitable for evaluating metagenome de novo assembly. We demonstrate that this new ensemble strategy tested using in silico spike-in, clinical and environmental NGS datasets achieved significantly better contigs than current approaches.",2015 Apr 20,"['Deng, Xutao', 'Naccache, Samia N.', 'Ng, Terry', 'Federman, Scot', 'Li, Linlin', 'Chiu, Charles Y.', 'Delwart, Eric L.']",Nucleic Acids Res,,,True
9d6c0c6b233bdffc9a3a85e7fe255163b54ca658,PMC,mRNA maturation in giant viruses: variation on a theme,http://dx.doi.org/10.1093/nar/gkv224,PMC4402537,25779049,CC BY,"Giant viruses from the Mimiviridae family replicate entirely in their host cytoplasm where their genes are transcribed by a viral transcription apparatus. mRNA polyadenylation uniquely occurs at hairpin-forming palindromic sequences terminating viral transcripts. Here we show that a conserved gene cluster both encode the enzyme responsible for the hairpin cleavage and the viral polyA polymerases (vPAP). Unexpectedly, the vPAPs are homodimeric and uniquely self-processive. The vPAP backbone structures exhibit a symmetrical architecture with two subdomains sharing a nucleotidyltransferase topology, suggesting that vPAPs originate from an ancestral duplication. A Poxvirus processivity factor homologue encoded by Megavirus chilensis displays a conserved 5′-GpppA 2′O methyltransferase activity but is also able to internally methylate the mRNAs’ polyA tails. These findings elucidate how the arm wrestling between hosts and their viruses to access the translation machinery is taking place in Mimiviridae.",2015 Apr 20,"['Priet, Stéphane', 'Lartigue, Audrey', 'Debart, Françoise', 'Claverie, Jean-Michel', 'Abergel, Chantal']",Nucleic Acids Res,,,True
e4bc8603739ef592b4ce5c2a3b92abd82a2a13ef,PMC,Preparation and Antibacterial Activity Evaluation of 18-β-glycyrrhetinic Acid Loaded PLGA Nanoparticles,,PMC4403053,25901144,CC BY,"The aim of the present study was to formulate poly (lactide-co-glycolide) (PLGA) nanoparticles loaded with 18-β-glycyrrhetinic acid (GLA) with appropriate physicochemical properties and antimicrobial activity. GLA loaded PLGA nanoparticles were prepared with different drug to polymer ratios, acetone contents and sonication times and the antibacterial activity of the developed nanoparticles was examined against different gram-negative and gram-positive bacteria. The antibacterial effect was studied using serial dilution technique to determine the minimum inhibitory concentration of nanoparticles. Results demonstrated that physicochemical properties of nanoparticles were affected by the above mentioned parameters where nanoscale size particles ranging from 175 to 212 nm were achieved. The highest encapsulation efficiency (53.2 ± 2.4%) was obtained when the ratio of drug to polymer was 1:4. Zeta potential of the developed nanoparticles was fairly negative (-11±1.5). In-vitro release profile of nanoparticles showed two phases: an initial phase of burst release for 10 h followed by a slow release pattern up to the end. The antimicrobial results revealed that the nanoparticles were more effective than pure GLA against P. aeuroginosa, S. aureus and S. epidermidis. This improvement in antibacterial activity of GLA loaded nanoparticles when compared to pure GLA may be related to higher nanoparticles penetration into infected cells and a higher amount of GLA delivery in its site of action. Herein, it was shown that GLA loaded PLGA nanoparticles displayed appropriate physicochemical properties as well as an improved antimicrobial effect.",2015 Spring,"['Darvishi, Behrad', 'Manoochehri, Saeed', 'Kamalinia, Golnaz', 'Samadi, Nasrin', 'Amini, Mohsen', 'Mostafavi, Seyyed Hossein', 'Maghazei, Shahab', 'Atyabi, Fatemeh', 'Dinarvand, Rassoul']",Iran J Pharm Res,,,True
c047b0340f79e0d34787e5f3500605b8c20e827d,PMC,Local Evolutionary Patterns of Human Respiratory Syncytial Virus Derived from Whole-Genome Sequencing,http://dx.doi.org/10.1128/JVI.03391-14,PMC4403408,25609811,CC BY,"Human respiratory syncytial virus (RSV) is associated with severe childhood respiratory infections. A clear description of local RSV molecular epidemiology, evolution, and transmission requires detailed sequence data and can inform new strategies for virus control and vaccine development. We have generated 27 complete or nearly complete genomes of RSV from hospitalized children attending a rural coastal district hospital in Kilifi, Kenya, over a 10-year period using a novel full-genome deep-sequencing process. Phylogenetic analysis of the new genomes demonstrated the existence and cocirculation of multiple genotypes in both RSV A and B groups in Kilifi. Comparison of local versus global strains demonstrated that most RSV A variants observed locally in Kilifi were also seen in other parts of the world, while the Kilifi RSV B genomes encoded a high degree of variation that was not observed in other parts of the world. The nucleotide substitution rates for the individual open reading frames (ORFs) were highest in the regions encoding the attachment (G) glycoprotein and the NS2 protein. The analysis of RSV full genomes, compared to subgenomic regions, provided more precise estimates of the RSV sequence changes and revealed important patterns of RSV genomic variation and global movement. The novel sequencing method and the new RSV genomic sequences reported here expand our knowledge base for large-scale RSV epidemiological and transmission studies. IMPORTANCE The new RSV genomic sequences and the novel sequencing method reported here provide important data for understanding RSV transmission and vaccine development. Given the complex interplay between RSV A and RSV B infections, the existence of local RSV B evolution is an important factor in vaccine deployment.",2015 Jan 21,"['Agoti, Charles N.', 'Otieno, James R.', 'Munywoki, Patrick K.', 'Mwihuri, Alexander G.', 'Cane, Patricia A.', 'Nokes, D. James', 'Kellam, Paul', 'Cotten, Matthew']",J Virol,,,True
50ff548ec63f21fdb34fbdfe8fab41141c65fcb5,PMC,Herpes Simplex Virus-1 Fine-Tunes Host’s Autophagic Response to Infection: A Comprehensive Analysis in Productive Infection Models,http://dx.doi.org/10.1371/journal.pone.0124646,PMC4403807,25894397,CC BY,"Herpes simplex virus-1 (HSV-1) infection causes severe conditions, with serious complications, including corneal blindness from uncontrolled ocular infections. An important cellular defense mechanism against HSV-1 infection is autophagy. The autophagic response of the host cell was suggested to be regulated by HSV-1. In this study, we performed a detailed analysis of autophagy in multiple HSV-1-targeted cell types, and under various infection conditions that recapitulate a productive infection model. We found that autophagy was slightly inhibited in one cell type, while in other cell types autophagy maintained its basal levels mostly unchanged during productive infection. This study refines the concept of HSV-1-mediated autophagy regulation to imply either inhibition, or prevention of activation, of the innate immune pathway.",2015 Apr 20,"['Yakoub, Abraam M.', 'Shukla, Deepak']",PLoS One,,,True
395fef2b73d1c568f900de94f5f6d908bc305f24,PMC,Detection of new genetic variants of Betacoronaviruses in Endemic Frugivorous Bats of Madagascar,http://dx.doi.org/10.1186/s12985-015-0271-y,PMC4404003,25888853,CC BY,"BACKGROUND: Bats are amongst the natural reservoirs of many coronaviruses (CoVs) of which some can lead to severe infection in human. African bats are known to harbor a range of pathogens (e.g., Ebola and Marburg viruses) that can infect humans and cause disease outbreaks. A recent study in South Africa isolated a genetic variant closely related to MERS-CoV from an insectivorous bat. Though Madagascar is home to 44 bat species (41 insectivorous and 3 frugivorous) of which 34 are endemic, no data exists concerning the circulation of CoVs in the island’s chiropteran fauna. Certain Malagasy bats can be frequently found in close contact with humans and frugivorous bats feed in the same trees where people collect and consume fruits and are hunted and consumed as bush meat. The purpose of our study is to detect and identify CoVs from frugivorous bats in Madagascar to evaluate the risk of human infection from infected bats. METHODS: Frugivorous bats belonging to three species were captured in four different regions of Madagascar. We analyzed fecal and throat swabs to detect the presence of virus through amplification of the RNA-dependent RNA polymerase (RdRp) gene, which is highly conserved in all known coronaviruses. Phylogenetic analyses were performed from positive specimens. RESULTS: From 351 frugivorous bats, we detected 14 coronaviruses from two endemic bats species, of which 13 viruses were identified from Pteropus rufus and one from Eidolon dupreanum, giving an overall prevalence of 4.5%. Phylogenetic analysis revealed that the Malagasy strains belong to the genus Betacoronavirus but form three distinct clusters, which seem to represent previously undescribed genetic lineages. CONCLUSIONS: Our findings suggest that CoVs circulate in frugivorous bats of Madagascar, demonstrating the needs to evaluate spillover risk to human populations especially for individuals that hunt and consume infected bats. Possible dispersal mechanisms as to how coronaviruses arrived on Madagascar are discussed.",2015 Mar 12,"['Razanajatovo, Norosoa H', 'Nomenjanahary, Lalaina A', 'Wilkinson, David A', 'Razafimanahaka, Julie H', 'Goodman, Steven M', 'Jenkins, Richard K', 'Jones, Julia PG', 'Heraud, Jean-Michel']",Virol J,,,True
72e1f47796b2283c03f3d7aa4f6044592f8c198d,PMC,An inactivated vaccine made from a U.S. field isolate of porcine epidemic disease virus is immunogenic in pigs as demonstrated by a dose-titration,http://dx.doi.org/10.1186/s12917-015-0357-1,PMC4404228,25881296,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV), a highly pathogenic and transmissible virus in swine, was first detected in the U.S. in May, 2013, and has caused tremendous losses to the swine industry. Due to the difficulty in isolating and growing this virus in cell culture, few vaccine studies using cell culture propagated PEDV have been performed on U.S. strains in pigs. Therefore, the objective of this study was to evaluate the humoral immune response to the selected inactivated PEDV vaccine candidate in a dose-titration manner. RESULTS: PEDV was isolated from a pig with diarrhea and complete genome sequencing found >99% nucleotide identity to other U.S. PEDV. Inactivated adjuvanted monovalent vaccines were administered intramuscularly to five week old pigs in a dose titration experimental design, ranging from 6.0-8.0 log(10) tissue culture infective dose (TCID(50)/mL), to evaluate immunogenicity using a fluorescent foci neutralization assay (FFN), fluorescent microsphere immunoassay (FMIA), and enzyme-linked immunosorbent assay (ELISA) on sera. Pigs vaccinated with 8.0 log(10) TCID(50)/mL inactivated virus showed significantly higher FFN titers as well as FMIA and ELISA values than 6.0 log(10) TCID(50)/mL vaccinates and the negative controls. CONCLUSIONS: These results demonstrate the immunogenicity of a PEDV inactivated viral vaccine with a U.S. strain via dose-titration. A future vaccination-challenge study would illustrate the efficacy of an inactivated vaccine and help evaluate protective FFN titers and ELISA and FMIA responses.",2015 Mar 15,"['Collin, Emily A', 'Anbalagan, Srivishnupriya', 'Okda, Faten', 'Batman, Ron', 'Nelson, Eric', 'Hause, Ben M']",BMC Vet Res,,,True
79ffac5ab7acd3c43a3e0866ed150fea9a0ec1c8,PMC,"BAP31, a promising target for the immunotherapy of malignant melanomas",http://dx.doi.org/10.1186/s13046-015-0153-6,PMC4405826,25903101,CC BY,"PURPOSE: Malignant melanoma’s (MM) incidence is rising faster than that of any other cancer in the US and the overall survival at 5 years is less than 10%. B cell associated protein 31 (BAP31) is overexpressed in most MMs and might be a promising target for immunotherapy of this disease. EXPERIMENTAL DESIGN: Firstly, we investigated the expression profiles of human BAP31 (hBAP31) and mouse BAP31 (mBAP31) in human and mouse normal tissues, respectively. The expression level of hBAP31 in human MMs and mBAP31 in B16 melanoma cells was also analyzed. Then we constructed novel mBAP31 DNA vaccines and tested there ability to stimulate mBAP31-specific immune responses and antitumor immunity in B16 melanoma-bearing mice. RESULTS: For the first time, we found that protein expression of hBAP31 were dramatically upregulated in human MMs when compared with human normal tissues. Predominant protein expression of mBAP31 was found in mouse B16 melanoma cells but not in mouse important organs. When mice were immunized with mBAP31 DNA vaccines, strong cellular response to mBAP31 was observed in the vaccinated mice. CTLs isolated from immunized mice could effectively kill mBAP31-positive target mouse B16 melanoma tumor cells in vitro and vaccination with mBAP31 DNA vaccines had potent anti-tumor activity in therapeutic model using B16 melanoma cells. CONCLUSIONS: These are the first data supporting a vaccine targeting BAP31 that is capable of inducing effective immunity against BAP31-expressing MMs and will be applicable to human MMs and hBAP31 DNA vaccine warrants investigation in human clinical trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-015-0153-6) contains supplementary material, which is available to authorized users.",2015 Apr 18,"['Yu, Shaojuan', 'Wang, Fuli', 'Fan, Li', 'Wei, Yuying', 'Li, Haitao', 'Sun, Yuanjie', 'Yang, Angang', 'Jin, Boquan', 'Song, Chaojun', 'Yang, Kun']",J Exp Clin Cancer Res,,,True
88e8809f280ef47d36f3e56b7f8558c303f36742,PMC,An educational programme for nursing college staff and students during a MERS- coronavirus outbreak in Saudi Arabia,http://dx.doi.org/10.1186/s12912-015-0065-y,PMC4405869,25904821,CC BY,"BACKGROUND: The Middle Eastern Respiratory Syndrome Coronavirus is a serious and emerging issue in Saudi Arabia and the world. A response was required to reduce possible disease transmission between the hospital and university. College of Nursing academic staff developed a programme in response to the educational and emotional needs of participants. METHODS: A MERS-CoV Task Force responded to the rapidly unfolding epidemic. The aim was to find out what nursing staff and nursing students in the college knew about MERS- CoV. While most gaps in knowledge were addressed after an intense information seminar, other learning needs were identified and responded to. The Task Force developed mandatory information sessions for all nursing faculty, students and staff. All staff were informed by email, letters and posters. There are 28 faculty staff, 84 support staff and 480 students in the College of Nursing. The information settings all took place within the College of Nursing, Princess Nourah University, Kingdom of Saudi Arabia. Questionnaires were given to faculty, students and staff to understand their baseline knowledge. After the sessions, faculty, students and staff were asked about what was learned through the sessions, and what educational needs still needed to be addressed. Approval was sought and received by the Ethics Committee for the College of Nursing. Participants completed informed consent forms and the voluntary nature of the study was explained. RESULTS: The total number of people attending the education sessions was133, including 65 students. 18 faculty members attended and 57 support staff. Data was gathered on gaps in participant knowledge and a plan was developed to address the gaps. Policies were established around student participation in clinical and return to work practices for staff with any symptoms. CONCLUSION: In hospitals there is above average risk for exposure to infectious diseases. Student nurses travel between hospital and university, with the capacity to act as a conduit of pathogens to large, susceptible populations. Nursing colleges must respond thoroughly to protect students and staff and prevent spread of disease into the university community in the midst of an epidemic.",2015 Apr 16,"['Stirling, Bridget V', 'Harmston, Jennie', 'Alsobayel, Hana']",BMC Nurs,,,True
424cd6cb670119aed604833cf1f107598f217574,PMC,Astragalin inhibits autophagy-associated airway epithelial fibrosis,http://dx.doi.org/10.1186/s12931-015-0211-9,PMC4406173,25895672,CC BY,"BACKGROUND: Fibrotic remodeling of airway and lung parenchymal compartments is attributed to pulmonary dysfunction with an involvement of reactive oxygen species (ROS) in chronic lung diseases such as idiopathic pulmonary fibrosis and asthma. METHODS: The in vitro study elucidated inhibitory effects of astragalin, kaempferol-3-O-glucoside from leaves of persimmon and green tea seeds, on oxidative stress-induced airway fibrosis. The in vivo study explored the demoting effects of astragalin on epithelial to mesenchymal transition in BALB/c mice sensitized with ovalbumin (OVA). RESULTS: The exposure of 20 μM H(2)O(2) for 72 h accelerated E-cadherin loss and vimentin induction in airway epithelial BEAS-2B cells, which was reversed by non-toxic astragalin at 1–20 μM. Astragalin allayed the airway tissue levels of ROS and vimentin enhanced by OVA challenge. Collagen type 1 production increased in H(2)O(2)–exposed epithelial cells and collagen fiber deposition was observed in OVA-challenged mouse airways. This study further investigated that the oxidative stress-triggered autophagic regulation was responsible for inducing airway fibrosis. H(2)O(2) highly enhanced the expression induction of the autophagy-related beclin-1 and light chains 3A/B (LC3A/B) within 4 h and astragalin blocked such induction by H(2)O(2). This compound deterred the ROS-promoted autophagosome formation in BEAS-2B cells. Consistently, in OVA-sensitized mice the expression of beclin-1 and LC3A/B was highly induced, and oral administration of astragalin suppressed the autophagosome formation with inhibiting the induction of these proteins in OVA-challenged airway subepithelium. Induction of autophagy by spermidine influenced the epithelial induction of E-cadherin and vimentin that was blocked by treating astragalin. CONCLUSION: These results demonstrate that astragalin can be effective in allaying ROS-promoted bronchial fibrosis through inhibiting autophagosome formation in airways.",2015 Apr 21,"['Cho, In-Hee', 'Choi, Yean-Jung', 'Gong, Ju-Hyun', 'Shin, Daekeun', 'Kang, Min-Kyung', 'Kang, Young-Hee']",Respir Res,,,True
e35886a4c45a6f26a17e68185b4172fb32ceb452,PMC,Isolation of Single-Stranded DNA Aptamers That Distinguish Influenza Virus Hemagglutinin Subtype H1 from H5,http://dx.doi.org/10.1371/journal.pone.0125060,PMC4406500,25901739,CC BY,"Surface protein hemagglutinin (HA) mediates the binding of influenza virus to host cell receptors containing sialic acid, facilitating the entry of the virus into host cells. Therefore, the HA protein is regarded as a suitable target for the development of influenza virus detection devices. In this study, we isolated single-stranded DNA (ssDNA) aptamers binding to the HA1 subunit of subtype H1 (H1-HA1), but not to the HA1 subunit of subtype H5 (H5-HA1), using a counter-systematic evolution of ligands by exponential enrichment (counter-SELEX) procedure. Enzyme-linked immunosorbent assay and surface plasmon resonance studies showed that the selected aptamers bind tightly to H1-HA1 with dissociation constants in the nanomolar range. Western blot analysis demonstrated that the aptamers were binding to H1-HA1 in a concentration-dependent manner, yet were not binding to H5-HA1. Interestingly, the selected aptamers contained G-rich sequences in the central random nucleotides region. Further biophysical analysis showed that the G-rich sequences formed a G-quadruplex structure, which is a distinctive structure compared to the starting ssDNA library. Using flow cytometry analysis, we found that the aptamers did not bind to the receptor-binding site of H1-HA1. These results indicate that the selected aptamers that distinguish H1-HA1 from H5-HA1 can be developed as unique probes for the detection of the H1 subtype of influenza virus.",2015 Apr 22,"['Woo, Hye-Min', 'Lee, Jin-Moo', 'Yim, Sanggyu', 'Jeong, Yong-Joo']",PLoS One,,,True
c1edf39ded74b76134cc304dd347a4eb20bae012,PMC,The Importance of Bacterial and Viral Infections Associated with Adult Asthma Exacerbations in Clinical Practice,http://dx.doi.org/10.1371/journal.pone.0123584,PMC4406689,25901797,CC BY,"BACKGROUND: Viral infection is one of the risk factors for asthma exacerbation. However, which pathogens are related to asthma exacerbation in adults remains unclear. OBJECTIVE: The relation between various infections and adult asthma exacerbations was investigated in clinical practice. METHODS: The study subjects included 50 adult inpatients due to asthma exacerbations and 20 stable outpatients for comparison. The pathogens from a nasopharyngeal swab were measured by multiplex PCR analysis. RESULTS: Asthma exacerbations occurred after a common cold in 48 inpatients. The numbers of patients with viral, bacterial, or both infections were 16, 9, and 9, respectively. The dominant viruses were rhinoviruses, respiratory syncytial virus, influenza virus, and metapneumovirus. The major bacteria were S. pneumoniae and H. influenzae. Compared to pathogen-free patients, the patients with pathogens were older and non-atopic and had later onset of disease, lower FeNO levels, lower IgE titers, and a higher incidence of comorbid sinusitis, COPD, or pneumonia. Compared to stable outpatients, asthma exacerbation inpatients had a higher incidence of smoking and comorbid sinusitis, COPD, or pneumonia. Viruses were detected in 50% of stable outpatients, but a higher incidence of rhinovirus, respiratory syncytial virus, and metapneumovirus infections was observed in asthma exacerbation inpatients. H. influenzae was observed in stable asthmatic patients. Other bacteria, especially S. pneumoniae, were important in asthma exacerbation inpatients. CONCLUSION: Viral or bacterial infections were observed in 70% of inpatients with an asthma exacerbation in clinical practice. Infection with S. pneumoniae was related to adult asthma exacerbation.",2015 Apr 22,"['Iikura, Motoyasu', 'Hojo, Masayuki', 'Koketsu, Rikiya', 'Watanabe, Sho', 'Sato, Ayano', 'Chino, Haruka', 'Ro, Shoki', 'Masaki, Haruna', 'Hirashima, Junko', 'Ishii, Satoru', 'Naka, Go', 'Takasaki, Jin', 'Izumi, Shinyu', 'Kobayashi, Nobuyuki', 'Yamaguchi, Sachiko', 'Nakae, Susumu', 'Sugiyama, Haruhito']",PLoS One,,,True
73f93646de4efa4c3b8d02d07dea684c028763d1,PMC,Investigation of Pathogenesis of H1N1 Influenza Virus and Swine Streptococcus suis Serotype 2 Co-Infection in Pigs by Microarray Analysis,http://dx.doi.org/10.1371/journal.pone.0124086,PMC4407888,25906258,CC BY,"Swine influenza virus and Streptococcus suis are two important contributors to the porcine respiratory disease complex, and both have significant economic impacts. Clinically, influenza virus and Streptococcus suis co-infections in pigs are very common, which often contribute to severe pneumonia and can increase the mortality. However, the co-infection pathogenesis in pigs is unclear. In the present study, co-infection experiments were performed using swine H1N1 influenza virus and Streptococcus suis serotype 2 (SS2). The H1N1-SS2 co-infected pigs exhibited more severe clinical symptoms, serious pathological changes, and robust apoptosis of lungs at 6 days post-infection compared with separate H1N1 and SS2 infections. A comprehensive gene expression profiling using a microarray approach was performed to investigate the global host responses of swine lungs against the swine H1N1 infection, SS2 infection, co-infection, and phosphate-buffered saline control. Results showed 457, 411, and 844 differentially expressed genes in the H1N1, SS2, and H1N1-SS2 groups, respectively, compared with the control. Noticeably, genes associated with the immune, inflammatory, and apoptosis responses were highly overexpressed in the co-infected group. Pathway analysis indicated that the cytokine–cytokine receptor interactions, MAPK, toll-like receptor, complement and coagulation cascades, antigen processing and presentation, and apoptosis pathway were significantly regulated in the co-infected group. However, the genes related to these were less regulated in the separate H1N1 and SS2 infection groups. This observation suggested that a certain level of synergy was induced by H1N1 and SS2 co-infection with significantly stronger inflammatory and apoptosis responses, which may lead to more serious respiratory disease syndrome and pulmonary pathological lesion.",2015 Apr 23,"['Lin, Xian', 'Huang, Canhui', 'Shi, Jian', 'Wang, Ruifang', 'Sun, Xin', 'Liu, Xiaokun', 'Zhao, Lianzhong', 'Jin, Meilin']",PLoS One,,,True
f74ee87b0db54450d2684da633a56b6f159a6c0b,PMC,The Ebola Epidemic Crystallizes the Potential of Passive Antibody Therapy for Infectious Diseases,http://dx.doi.org/10.1371/journal.ppat.1004717,PMC4408073,25905897,CC BY,,2015 Apr 23,"['Casadevall, Arturo', 'Pirofski, Liise-anne']",PLoS Pathog,,,True
7b1a62bfe713b9fe81bb84360d31590a6083b499,PMC,A Functional Role of Fibroblast Growth Factor Receptor 1 (FGFR1) in the Suppression of Influenza A Virus Replication,http://dx.doi.org/10.1371/journal.pone.0124651,PMC4409105,25909503,CC BY,"Influenza A virus causes annual epidemics and occasional pandemics in humans. Here, we investigated four members of the fibroblast growth factor receptor (FGFR) family; FGFR1 to 4, and examined their expression patterns in human lung epithelial cells A549 with influenza A virus infection. We identified a functional role of FGFR1 in influenza A/Puerto Rico/8/1934 (PR8) and A/Anhui/01/2005 (H5N1) virus replication. Our results showed that FGFR1 silencing by siRNA interference promoted influenza A/PR8 and H5N1 virus replication in A549 cells, while lentivirus-mediated exogenous FGFR1 expression significantly suppressed influenza A virus replication; however, FGFR4 did not have the same effects. Moreover, FGFR1 phosphorylation levels were downregulated in A549 cells by influenza A virus infection, while the repression of FGFR1 kinase using PD173074, a potent and selective FGFR1 inhibitor, could enhance virus replication. Furthermore, we found that FGFR1 inhibits influenza virus internalization, but not binding, during viral entry. These results suggested that FGFR1 specifically antagonizes influenza A virus replication, probably by blocking viral entry.",2015 Apr 24,"['Liu, Xin', 'Lai, Chengcai', 'Wang, Keyu', 'Xing, Li', 'Yang, Penghui', 'Duan, Qing', 'Wang, Xiliang']",PLoS One,,,True
88ccb20962dc958fc239c0ef5bed963cfd782b65,PMC,The Ebola epidemic is ongoing in West Africa and responses from China are positive,http://dx.doi.org/10.1186/s40779-015-0031-8,PMC4409763,25914830,CC BY,"The ongoing Ebola outbreak poses an alarming risk to the countries of West Africa and beyond. On August 8, 2014, the World Health Organization (WHO) declared the cross-country Ebola outbreak a Public Emergency of International Concern. China has had no confirmed cases of Ebola. In this paper, virologic characteristics, pathogenesis, clinical manifestations, laboratory examination and prophylactic vaccines and therapeutic drugs of Ebola are summarized. Importantly, active responses and actions from China are introduced. Moreover, the key issues in the future prevention and control of Ebola were also addressed.",2015 Apr 3,"['Zhao, Jing-Min', 'Dong, Shi-Jun', 'Li, Jin', 'Ji, Jun-Sheng']",Mil Med Res,,,True
c8233094deb36e03c7c73fd03f3bab601498e563,PMC,A comprehensive collection of systems biology data characterizing the host response to viral infection,http://dx.doi.org/10.1038/sdata.2014.33,PMC4410982,25977790,CC BY,"The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archived at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). By comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection.",2014 Oct 14,"['Aevermann, Brian D.', 'Pickett, Brett E.', 'Kumar, Sanjeev', 'Klem, Edward B.', 'Agnihothram, Sudhakar', 'Askovich, Peter S.', 'Bankhead, Armand', 'Bolles, Meagen', 'Carter, Victoria', 'Chang, Jean', 'Clauss, Therese R.W.', 'Dash, Pradyot', 'Diercks, Alan H.', 'Eisfeld, Amie J.', 'Ellis, Amy', 'Fan, Shufang', 'Ferris, Martin T.', 'Gralinski, Lisa E.', 'Green, Richard R.', 'Gritsenko, Marina A.', 'Hatta, Masato', 'Heegel, Robert A.', 'Jacobs, Jon M.', 'Jeng, Sophia', 'Josset, Laurence', 'Kaiser, Shari M.', 'Kelly, Sara', 'Law, G. Lynn', 'Li, Chengjun', 'Li, Jiangning', 'Long, Casey', 'Luna, Maria L.', 'Matzke, Melissa', 'McDermott, Jason', 'Menachery, Vineet', 'Metz, Thomas O.', 'Mitchell, Hugh', 'Monroe, Matthew E.', 'Navarro, Garnet', 'Neumann, Gabriele', 'Podyminogin, Rebecca L.', 'Purvine, Samuel O.', 'Rosenberger, Carrie M.', 'Sanders, Catherine J.', 'Schepmoes, Athena A.', 'Shukla, Anil K.', 'Sims, Amy', 'Sova, Pavel', 'Tam, Vincent C.', 'Tchitchek, Nicolas', 'Thomas, Paul G.', 'Tilton, Susan C.', 'Totura, Allison', 'Wang, Jing', 'Webb-Robertson, Bobbie-Jo', 'Wen, Ji', 'Weiss, Jeffrey M.', 'Yang, Feng', 'Yount, Boyd', 'Zhang, Qibin', 'McWeeney, Shannon', 'Smith, Richard D.', 'Waters, Katrina M.', 'Kawaoka, Yoshihiro', 'Baric, Ralph', 'Aderem, Alan', 'Katze, Michael G.', 'Scheuermann, Richard H.']",Sci Data,,,True
d17d178051c8b4585dd66e5bd7133508b3bc2402,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,True
a60d8041651d988fe83f9d4def187dcec19e1b66,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
da3696f40f9fff27f4b2f2789526d6b0c81f899d,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
edc05633e04aec4493d6cb261f350e54391a2edb,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
94ebd991caf3c3fc8561d9ad165390c51fa67757,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
4891cafcdb90b9702d6081f319821128e5d368a0,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
9dcc65d991c6dc72487b7f9029097afad9f9d424,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
e7eb17bb7d285c2cbe084a2784f3d0decc05e9b7,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
db4b37fcb72b1a2aeaee7543840c6c5fd454867c,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
f03bbdf1292de07aefe78b58be581fabb2871325,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
affb6d09adb3ae7026f16be723735c1b0618e62f,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
b0e58214e1fcc36ae225b63fdaa85c3b98a2f0d0,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
e1363cfecc17035806dcf538c125b767cbc2da76,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
f764ceedc21a1f591bc92f09e46c3642483c556a,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
30dd652d4018a27fc531e9a9e9a17f154dea4431,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
1b77215769da2e43a11ea56da546a7fa6fcc9fe8,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
b0afa69f8bdf0d33afde64ae9ce1350e765e156c,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
abb2571a4c8f492dc552c761f076bbc2399d6fa1,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
4a79c933be9a09ed991368789689d63be064d038,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
165dd8a7bdeb7b18f7226a13ff23b8da2504c93d,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
b46a45f5875bb38ef2b8590cf7ae92e829eba5e4,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
f0cee74f65b4b34666a289e300164727a3da3ff4,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
5e8224da4332ec3b3998882fc55e494c9a695ede,PMC,A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1004848,PMC4411065,25915054,CC BY,"Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.",2015 Apr 27,"['Xiao, Xiaoping', 'Zhang, Rudian', 'Pang, Xiaojing', 'Liang, Guodong', 'Wang, Penghua', 'Cheng, Gong']",PLoS Pathog,,,False
ddbf31002935c6a62e177e3085670455ec4121ec,PMC,Progress and Challenges toward the Development of Vaccines against Avian Infectious Bronchitis,http://dx.doi.org/10.1155/2015/424860,PMC4411447,25954763,CC BY,"Avian infectious bronchitis (IB) is a widely distributed poultry disease that has huge economic impact on poultry industry. The continuous emergence of new IBV genotypes and lack of cross protection among different IBV genotypes have been an important challenge. Although live attenuated IB vaccines remarkably induce potent immune response, the potential risk of reversion to virulence, neutralization by the maternal antibodies, and recombination and mutation events are important concern on their usage. On the other hand, inactivated vaccines induce a weaker immune response and may require multiple dosing and/or the use of adjuvants that probably have potential safety risks and increased economic burdens. Consequently, alternative IB vaccines are widely sought. Recent advances in recombinant DNA technology have resulted in experimental IB vaccines that show promise in antibody and T-cells responses, comparable to live attenuated vaccines. Recombinant DNA vaccines have also been enhanced to target multiple serotypes and their efficacy has been improved using delivery vectors, nanoadjuvants, and in ovo vaccination approaches. Although most recombinant IB DNA vaccines are yet to be licensed, it is expected that these types of vaccines may hold sway as future vaccines for inducing a cross protection against multiple IBV serotypes.",2015 Apr 14,"['Bande, Faruku', 'Arshad, Siti Suri', 'Hair Bejo, Mohd', 'Moeini, Hassan', 'Omar, Abdul Rahman']",J Immunol Res,,,True
a4f3abb6d4a6463835878af8817389b825347d7b,PMC,"Influence of age, severity of infection, and co-infection on the duration of respiratory syncytial virus (RSV) shedding",http://dx.doi.org/10.1017/S0950268814001393,PMC4411640,24901443,CC BY,"RSV is the most important viral cause of pneumonia and bronchiolitis in children worldwide and has been associated with significant disease burden. With the renewed interest in RSV vaccines, we provide realistic estimates on duration, and influencing factors on RSV shedding which are required to better understand the impact of vaccination on the virus transmission dynamics. The data arise from a prospective study of 47 households (493 individuals) in rural Kenya, followed through a 6-month period of an RSV seasonal outbreak. Deep nasopharyngeal swabs were collected twice each week from all household members, irrespective of symptoms, and tested for RSV by multiplex PCR. The RSV G gene was sequenced. A total of 205 RSV infection episodes were detected in 179 individuals from 40 different households. The infection data were interval censored and assuming a random event time between observations, the average duration of virus shedding was 11·2 (95% confidence interval 10·1–12·3) days. The shedding durations were longer than previous estimates (3·9–7·4 days) based on immunofluorescence antigen detection or viral culture, and were shown to be strongly associated with age, severity of infection, and revealed potential interaction with other respiratory viruses. These findings are key to our understanding of the spread of this important virus and are relevant in the design of control programmes.",2015 Mar 5,"['MUNYWOKI, P. K.', 'KOECH, D. C.', 'AGOTI, C. N.', 'KIBIRIGE, N.', 'KIPKOECH, J.', 'CANE, P. A.', 'MEDLEY, G. F.', 'NOKES, D. J.']",Epidemiol Infect,,,True
73c2606bc45a573294360406628a8edd45bdd511,PMC,Use of linked electronic health records to assess mortality and length of stay associated with pandemic influenza A(H1N1)pdm09 at a UK teaching hospital,http://dx.doi.org/10.1017/S0950268814002076,PMC4411648,25119499,CC BY,"Effective use of data linkage is becoming an increasingly important focus in the new healthcare system in England. We linked data from the results of a multiplex PCR assay for respiratory viruses for a population of 230 inpatients at a UK teaching hospital with their patient administrative system records in order to compare the mortality and length of stay of patients who tested positive for influenza A(H1N1)pdm09 with those positive for another influenza A virus. The results indicated a reduced risk of death among influenza A(H1N1)pdm09 patients compared to other influenza A strains, with an adjusted risk ratio of 0·25 (95% confidence interval 0·08–0·75, P = 0·01), while no significant differences were found between the lengths of stay in the hospital for these two groups. Further development of such methods to link hospital data in a routine fashion could provide a rapid means of gaining epidemiological insights into emerging infectious diseases.",2015 Apr 14,"['Smith, C.', 'Curran, M. D.', 'Roddick, I.', 'Reacher, M.']",Epidemiol Infect,,,True
379317c0c8b61dd88b6faa235b21dd861436edcf,PMC,Incorporation of Spike and Membrane Glycoproteins into Coronavirus Virions,http://dx.doi.org/10.3390/v7041700,PMC4411675,25855243,CC BY,"The envelopes of coronaviruses (CoVs) contain primarily three proteins; the two major glycoproteins spike (S) and membrane (M), and envelope (E), a non-glycosylated protein. Unlike other enveloped viruses, CoVs bud and assemble at the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC). For efficient virion assembly, these proteins must be targeted to the budding site and to interact with each other or the ribonucleoprotein. Thus, the efficient incorporation of viral envelope proteins into CoV virions depends on protein trafficking and protein–protein interactions near the ERGIC. The goal of this review is to summarize recent findings on the mechanism of incorporation of the M and S glycoproteins into the CoV virion, focusing on protein trafficking and protein–protein interactions.",2015 Apr 3,"['Ujike, Makoto', 'Taguchi, Fumihiro']",Viruses,,,True
902ec7158906ac390bdc04cd55350a12c8a39281,PMC,The Evolution of Poxvirus Vaccines,http://dx.doi.org/10.3390/v7041726,PMC4411676,25853483,CC BY,"After Edward Jenner established human vaccination over 200 years ago, attenuated poxviruses became key players to contain the deadliest virus of its own family: Variola virus (VARV), the causative agent of smallpox. Cowpox virus (CPXV) and horsepox virus (HSPV) were extensively used to this end, passaged in cattle and humans until the appearance of vaccinia virus (VACV), which was used in the final campaigns aimed to eradicate the disease, an endeavor that was accomplished by the World Health Organization (WHO) in 1980. Ever since, naturally evolved strains used for vaccination were introduced into research laboratories where VACV and other poxviruses with improved safety profiles were generated. Recombinant DNA technology along with the DNA genome features of this virus family allowed the generation of vaccines against heterologous diseases, and the specific insertion and deletion of poxvirus genes generated an even broader spectrum of modified viruses with new properties that increase their immunogenicity and safety profile as vaccine vectors. In this review, we highlight the evolution of poxvirus vaccines, from first generation to the current status, pointing out how different vaccines have emerged and approaches that are being followed up in the development of more rational vaccines against a wide range of diseases.",2015 Apr 7,"['Sánchez-Sampedro, Lucas', 'Perdiguero, Beatriz', 'Mejías-Pérez, Ernesto', 'García-Arriaza, Juan', 'Di Pilato, Mauro', 'Esteban, Mariano']",Viruses,,,True
4271774baf0182630ce43862b9e0b151eda34e8c,PMC,"Insect-Specific Flaviviruses: A Systematic Review of Their Discovery, Host Range, Mode of Transmission, Superinfection Exclusion Potential and Genomic Organization",http://dx.doi.org/10.3390/v7041927,PMC4411683,25866904,CC BY,"There has been a dramatic increase in the number of insect-specific flaviviruses (ISFs) discovered in the last decade. Historically, these viruses have generated limited interest due to their inability to infect vertebrate cells. This viewpoint has changed in recent years because some ISFs have been shown to enhance or suppress the replication of medically important flaviviruses in co-infected mosquito cells. Additionally, comparative studies between ISFs and medically important flaviviruses can provide a unique perspective as to why some flaviviruses possess the ability to infect and cause devastating disease in humans while others do not. ISFs have been isolated exclusively from mosquitoes in nature but the detection of ISF-like sequences in sandflies and chironomids indicates that they may also infect other dipterans. ISFs can be divided into two distinct phylogenetic groups. The first group currently consists of approximately 12 viruses and includes cell fusing agent virus, Kamiti River virus and Culex flavivirus. These viruses are phylogenetically distinct from all other known flaviviruses. The second group, which is apparently not monophyletic, currently consists of nine viruses and includes Chaoyang virus, Nounané virus and Lammi virus. These viruses phylogenetically affiliate with mosquito/vertebrate flaviviruses despite their apparent insect-restricted phenotype. This article provides a review of the discovery, host range, mode of transmission, superinfection exclusion ability and genomic organization of ISFs. This article also attempts to clarify the ISF nomenclature because some of these viruses have been assigned more than one name due to their simultaneous discoveries by independent research groups.",2015 Apr 10,"['Blitvich, Bradley J.', 'Firth, Andrew E.']",Viruses,,,True
a4f9f7c80a7abba6f1d211cfd5b53ee14bb47000,PMC,Livestock trade networks for guiding animal health surveillance,http://dx.doi.org/10.1186/s12917-015-0354-4,PMC4411738,25889738,CC BY,"BACKGROUND: Trade in live animals can contribute to the introduction of exotic diseases, the maintenance and spread endemic diseases. Annually millions of animals are moved across Europe for the purposes of breeding, fattening and slaughter. Data on the number of animals moved were obtained from the Directorate General Sanco (DG Sanco) for 2011. These were converted to livestock units to enable direct comparison across species and their movements were mapped, used to calculate the indegrees and outdegrees of 27 European countries and the density and transitivity of movements within Europe. This provided the opportunity to discuss surveillance of European livestock movement taking into account stopping points en-route. RESULTS: High density and transitivity of movement for registered equines, breeding and fattening cattle, breeding poultry and pigs for breeding, fattening and slaughter indicates that hazards have the potential to spread quickly within these populations. This is of concern to highly connected countries particularly those where imported animals constitute a large proportion of their national livestock populations, and have a high indegree. The transport of poultry (older than 72 hours) and unweaned animals would require more rest breaks than the movement of weaned animals, which may provide more opportunities for disease transmission. Transitivity is greatest for animals transported for breeding purposes with cattle, pigs and poultry having values of over 50%. CONCLUSIONS: This paper demonstrated that some species (pigs and poultry) are traded much more frequently and at a larger scale than species such as goats. Some countries are more vulnerable than others due to importing animals from many countries, having imported animals requiring rest-breaks and importing large proportions of their national herd or flock. Such knowledge about the vulnerability of different livestock systems related to trade movements can be used to inform the design of animal health surveillance systems to facilitate the trade in animals between European member states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0354-4) contains supplementary material, which is available to authorized users.",2015 Apr 1,"['Hardstaff, Jo L', 'Häsler, Barbara', 'Rushton, Jonathan R']",BMC Vet Res,,,False
4f7f915e27fdb16ed137f0b0738f865a53a54343,PMC,Livestock trade networks for guiding animal health surveillance,http://dx.doi.org/10.1186/s12917-015-0354-4,PMC4411738,25889738,CC BY,"BACKGROUND: Trade in live animals can contribute to the introduction of exotic diseases, the maintenance and spread endemic diseases. Annually millions of animals are moved across Europe for the purposes of breeding, fattening and slaughter. Data on the number of animals moved were obtained from the Directorate General Sanco (DG Sanco) for 2011. These were converted to livestock units to enable direct comparison across species and their movements were mapped, used to calculate the indegrees and outdegrees of 27 European countries and the density and transitivity of movements within Europe. This provided the opportunity to discuss surveillance of European livestock movement taking into account stopping points en-route. RESULTS: High density and transitivity of movement for registered equines, breeding and fattening cattle, breeding poultry and pigs for breeding, fattening and slaughter indicates that hazards have the potential to spread quickly within these populations. This is of concern to highly connected countries particularly those where imported animals constitute a large proportion of their national livestock populations, and have a high indegree. The transport of poultry (older than 72 hours) and unweaned animals would require more rest breaks than the movement of weaned animals, which may provide more opportunities for disease transmission. Transitivity is greatest for animals transported for breeding purposes with cattle, pigs and poultry having values of over 50%. CONCLUSIONS: This paper demonstrated that some species (pigs and poultry) are traded much more frequently and at a larger scale than species such as goats. Some countries are more vulnerable than others due to importing animals from many countries, having imported animals requiring rest-breaks and importing large proportions of their national herd or flock. Such knowledge about the vulnerability of different livestock systems related to trade movements can be used to inform the design of animal health surveillance systems to facilitate the trade in animals between European member states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0354-4) contains supplementary material, which is available to authorized users.",2015 Apr 1,"['Hardstaff, Jo L', 'Häsler, Barbara', 'Rushton, Jonathan R']",BMC Vet Res,,,False
b5c63a3728bd54d804043f60a51594f39959b0e5,PMC,Livestock trade networks for guiding animal health surveillance,http://dx.doi.org/10.1186/s12917-015-0354-4,PMC4411738,25889738,CC BY,"BACKGROUND: Trade in live animals can contribute to the introduction of exotic diseases, the maintenance and spread endemic diseases. Annually millions of animals are moved across Europe for the purposes of breeding, fattening and slaughter. Data on the number of animals moved were obtained from the Directorate General Sanco (DG Sanco) for 2011. These were converted to livestock units to enable direct comparison across species and their movements were mapped, used to calculate the indegrees and outdegrees of 27 European countries and the density and transitivity of movements within Europe. This provided the opportunity to discuss surveillance of European livestock movement taking into account stopping points en-route. RESULTS: High density and transitivity of movement for registered equines, breeding and fattening cattle, breeding poultry and pigs for breeding, fattening and slaughter indicates that hazards have the potential to spread quickly within these populations. This is of concern to highly connected countries particularly those where imported animals constitute a large proportion of their national livestock populations, and have a high indegree. The transport of poultry (older than 72 hours) and unweaned animals would require more rest breaks than the movement of weaned animals, which may provide more opportunities for disease transmission. Transitivity is greatest for animals transported for breeding purposes with cattle, pigs and poultry having values of over 50%. CONCLUSIONS: This paper demonstrated that some species (pigs and poultry) are traded much more frequently and at a larger scale than species such as goats. Some countries are more vulnerable than others due to importing animals from many countries, having imported animals requiring rest-breaks and importing large proportions of their national herd or flock. Such knowledge about the vulnerability of different livestock systems related to trade movements can be used to inform the design of animal health surveillance systems to facilitate the trade in animals between European member states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0354-4) contains supplementary material, which is available to authorized users.",2015 Apr 1,"['Hardstaff, Jo L', 'Häsler, Barbara', 'Rushton, Jonathan R']",BMC Vet Res,,,False
862715a714155bda6a996da96ed692ca426666a2,PMC,Livestock trade networks for guiding animal health surveillance,http://dx.doi.org/10.1186/s12917-015-0354-4,PMC4411738,25889738,CC BY,"BACKGROUND: Trade in live animals can contribute to the introduction of exotic diseases, the maintenance and spread endemic diseases. Annually millions of animals are moved across Europe for the purposes of breeding, fattening and slaughter. Data on the number of animals moved were obtained from the Directorate General Sanco (DG Sanco) for 2011. These were converted to livestock units to enable direct comparison across species and their movements were mapped, used to calculate the indegrees and outdegrees of 27 European countries and the density and transitivity of movements within Europe. This provided the opportunity to discuss surveillance of European livestock movement taking into account stopping points en-route. RESULTS: High density and transitivity of movement for registered equines, breeding and fattening cattle, breeding poultry and pigs for breeding, fattening and slaughter indicates that hazards have the potential to spread quickly within these populations. This is of concern to highly connected countries particularly those where imported animals constitute a large proportion of their national livestock populations, and have a high indegree. The transport of poultry (older than 72 hours) and unweaned animals would require more rest breaks than the movement of weaned animals, which may provide more opportunities for disease transmission. Transitivity is greatest for animals transported for breeding purposes with cattle, pigs and poultry having values of over 50%. CONCLUSIONS: This paper demonstrated that some species (pigs and poultry) are traded much more frequently and at a larger scale than species such as goats. Some countries are more vulnerable than others due to importing animals from many countries, having imported animals requiring rest-breaks and importing large proportions of their national herd or flock. Such knowledge about the vulnerability of different livestock systems related to trade movements can be used to inform the design of animal health surveillance systems to facilitate the trade in animals between European member states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0354-4) contains supplementary material, which is available to authorized users.",2015 Apr 1,"['Hardstaff, Jo L', 'Häsler, Barbara', 'Rushton, Jonathan R']",BMC Vet Res,,,False
2cedf6edf59b93290a68074986ee680c8c8e89a1,PMC,Livestock trade networks for guiding animal health surveillance,http://dx.doi.org/10.1186/s12917-015-0354-4,PMC4411738,25889738,CC BY,"BACKGROUND: Trade in live animals can contribute to the introduction of exotic diseases, the maintenance and spread endemic diseases. Annually millions of animals are moved across Europe for the purposes of breeding, fattening and slaughter. Data on the number of animals moved were obtained from the Directorate General Sanco (DG Sanco) for 2011. These were converted to livestock units to enable direct comparison across species and their movements were mapped, used to calculate the indegrees and outdegrees of 27 European countries and the density and transitivity of movements within Europe. This provided the opportunity to discuss surveillance of European livestock movement taking into account stopping points en-route. RESULTS: High density and transitivity of movement for registered equines, breeding and fattening cattle, breeding poultry and pigs for breeding, fattening and slaughter indicates that hazards have the potential to spread quickly within these populations. This is of concern to highly connected countries particularly those where imported animals constitute a large proportion of their national livestock populations, and have a high indegree. The transport of poultry (older than 72 hours) and unweaned animals would require more rest breaks than the movement of weaned animals, which may provide more opportunities for disease transmission. Transitivity is greatest for animals transported for breeding purposes with cattle, pigs and poultry having values of over 50%. CONCLUSIONS: This paper demonstrated that some species (pigs and poultry) are traded much more frequently and at a larger scale than species such as goats. Some countries are more vulnerable than others due to importing animals from many countries, having imported animals requiring rest-breaks and importing large proportions of their national herd or flock. Such knowledge about the vulnerability of different livestock systems related to trade movements can be used to inform the design of animal health surveillance systems to facilitate the trade in animals between European member states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0354-4) contains supplementary material, which is available to authorized users.",2015 Apr 1,"['Hardstaff, Jo L', 'Häsler, Barbara', 'Rushton, Jonathan R']",BMC Vet Res,,,True
03fa4232b3fbc44b6029d52c3120f4e82fdc49c0,PMC,Human coronavirus OC43 3CL protease and the potential of ML188 as a broad-spectrum lead compound: Homology modelling and molecular dynamic studies,http://dx.doi.org/10.1186/s12900-015-0035-3,PMC4411765,25928480,CC BY,"BACKGROUND: The coronavirus 3 chymotrypsin-like protease (3CL(pro)) is a validated target in the design of potential anticoronavirus inhibitors. The high degree of homology within the protease’s active site and substrate conservation supports the identification of broad spectrum lead compounds. A previous study identified the compound ML188, also termed 16R, as an inhibitor of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) 3CL(pro). This study will detail the generation of a homology model of the 3CL(pro) of the human coronavirus OC43 and determine the potential of 16R to form a broad-spectrum lead compound. MODELLER was used to generate a suitable three-dimensional model of the OC43 3CL(pro) and the Prime module of Schrӧdinger predicted the binding conformation and free energy of binding of 16R within the 3CL(pro) active site. Molecular dynamics further confirmed ligand stability and hydrogen bonding networks. RESULTS: A high quality homology model of the OC43 3CL(pro) was successfully generated in an active conformation. Further studies reproduced the binding pose of 16R within the active site of the generated model, where its free energy of binding was shown to equal that of the 3CL(pro) of SARS-CoV, a receptor it is experimentally proven to inhibit. The stability of the ligand was subsequently confirmed by molecular dynamics. CONCLUSION: The lead compound 16R may represent a broad-spectrum inhibitor of the 3CL(pro) of OC43 and potentially other coronaviruses. This study provides an atomistic structure of the 3CL(pro) of OC43 and supports further experimental validation of the inhibitory effects of 16R. These findings further confirm that the 3CL(pro) of coronaviruses can be inhibited by broad spectrum lead compounds.",2015 Apr 28,"['Berry, Michael', 'Fielding, Burtram', 'Gamieldien, Junaid']",BMC Struct Biol,,,True
9d089a2632f7a6fc75d5e723ebe2ac9db15c0048,PMC,CD200 Receptor Restriction of Myeloid Cell Responses Antagonizes Antiviral Immunity and Facilitates Cytomegalovirus Persistence within Mucosal Tissue,http://dx.doi.org/10.1371/journal.ppat.1004641,PMC4412112,25654642,CC BY,"CD200 receptor (CD200R) negatively regulates peripheral and mucosal innate immune responses. Viruses, including herpesviruses, have acquired functional CD200 orthologs, implying that viral exploitation of this pathway is evolutionary advantageous. However, the role that CD200R signaling plays during herpesvirus infection in vivo requires clarification. Utilizing the murine cytomegalovirus (MCMV) model, we demonstrate that CD200R facilitates virus persistence within mucosal tissue. Specifically, MCMV infection of CD200R-deficient mice (CD200R(-/-)) elicited heightened mucosal virus-specific CD4 T cell responses that restricted virus persistence in the salivary glands. CD200R did not directly inhibit lymphocyte effector function. Instead, CD200R(-/-) mice exhibited enhanced APC accumulation that in the mucosa was a consequence of elevated cellular proliferation. Although MCMV does not encode an obvious CD200 homolog, productive replication in macrophages induced expression of cellular CD200. CD200 from hematopoietic and non-hematopoietic cells contributed independently to suppression of antiviral control in vivo. These results highlight the CD200-CD200R pathway as an important regulator of antiviral immunity during cytomegalovirus infection that is exploited by MCMV to establish chronicity within mucosal tissue.",2015 Feb 5,"['Stack, Gabrielle', 'Jones, Emma', 'Marsden, Morgan', 'Stacey, Maria A.', 'Snelgrove, Robert J.', 'Lacaze, Paul', 'Jacques, Laura C.', 'Cuff, Simone M.', 'Stanton, Richard J.', 'Gallimore, Awen M.', 'Hussell, Tracy', 'Wilkinson, Gavin W. G.', 'Ghazal, Peter', 'Taylor, Philip R.', 'Humphreys, Ian R.']",PLoS Pathog,,,True
4eca3df95a8bf82f07ba51b6978bd4049f8df827,PMC,Laboratory Investigation and Phylogenetic Analysis of an Imported Middle East Respiratory Syndrome Coronavirus Case in Greece,http://dx.doi.org/10.1371/journal.pone.0125809,PMC4412533,25919137,CC0,"Rapid and reliable laboratory diagnosis of persons suspected of Middle East respiratory syndrome coronavirus (MERS-CoV) infection is important for timely implementation of infection control practices and disease management. In addition, monitoring molecular changes in the virus can help elucidate chains of transmission and identify mutations that might influence virus transmission efficiency. This was illustrated by a recent laboratory investigation we conducted on an imported MERS-CoV case in Greece. Two oropharyngeal swab specimens were collected on the 1(st) and 2(nd) day of patient hospitalization and tested using two real-time RT-PCR (rRT-PCR) assays targeting the UpE and Orf-1a regions of the MERS-CoV genome and RT-PCR and partial sequencing of RNA-dependent RNA polymerase and nucleocapsid genes. Serum specimens were also collected and serological test were performed. Results from the first swab sample were inconclusive while the second swab was strongly positive for MERS-CoV RNA by rRT-PCR and confirmed positive by RT-PCR and partial gene sequencing. Positive serologic test results further confirmed MERS-CoV infection. Full-length nucleocapsid and spike gene coding sequences were later obtained from the positive swab sample. Phylogenetic analysis revealed that the virus was closely related to recent human-derived MERS-CoV strains obtained in Jeddah and Makkah, Saudi Arabia, in April 2014 and dromedary camels in Saudi Arabia and Qatar. These findings were consistent with the patient’s history. We also identified a unique amino acid substitution in the spike receptor binding domain that may have implications for receptor binding efficiency. Our initial inconclusive rRT-PCR results highlight the importance of collecting multiple specimens from suspect MERS-CoV cases and particularly specimens from the lower respiratory tract.",2015 Apr 28,"['Kossyvakis, Athanasios', 'Tao, Ying', 'Lu, Xiaoyan', 'Pogka, Vasiliki', 'Tsiodras, Sotirios', 'Emmanouil, Mary', 'Mentis, Andreas F.', 'Tong, Suxiang', 'Erdman, Dean D.', 'Antoniadis, Antonios']",PLoS One,,,True
6bd542932368c6d6a32847714e3327136f3c4bd8,PMC,Pseudotype-Based Neutralization Assays for Influenza: A Systematic Analysis,http://dx.doi.org/10.3389/fimmu.2015.00161,PMC4413832,25972865,CC BY,"The use of vaccination against the influenza virus remains the most effective method of mitigating the significant morbidity and mortality caused by this virus. Antibodies elicited by currently licensed influenza vaccines are predominantly hemagglutination-inhibition (HI)-competent antibodies that target the globular head of hemagglutinin (HA) thus inhibiting influenza virus entry into target cells. These antibodies predominantly confer homosubtypic/strain specific protection and only rarely confer heterosubtypic protection. However, recent academia or pharma-led R&D toward the production of a “universal vaccine” has centered on the elicitation of antibodies directed against the stalk of the influenza HA that has been shown to confer broad protection across a range of different subtypes (H1–H16). The accurate and sensitive measurement of antibody responses elicited by these “next-generation” influenza vaccines is, however, hampered by the lack of sensitivity of the traditional influenza serological assays HI, single radial hemolysis, and microneutralization. Assays utilizing pseudotypes, chimeric viruses bearing influenza glycoproteins, have been shown to be highly efficient for the measurement of homosubtypic and heterosubtypic broadly neutralizing antibodies, making them ideal serological tools for the study of cross-protective responses against multiple influenza subtypes with pandemic potential. In this review, we will analyze and compare literature involving the production of influenza pseudotypes with particular emphasis on their use in serum antibody neutralization assays. This will enable us to establish the parameters required for optimization and propose a consensus protocol to be employed for the further deployment of these assays in influenza vaccine immunogenicity studies.",2015 Apr 29,"['Carnell, George William', 'Ferrara, Francesca', 'Grehan, Keith', 'Thompson, Craig Peter', 'Temperton, Nigel James']",Front Immunol,,,True
65dad274ae49f213826f7cb5c43415778e053ce0,PMC,Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD,http://dx.doi.org/10.1038/srep09927,PMC4413879,25923474,CC BY,"Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations.",2015 Apr 29,"['Sundar, Isaac K.', 'Ahmad, Tanveer', 'Yao, Hongwei', 'Hwang, Jae-woong', 'Gerloff, Janice', 'Lawrence, B. Paige', 'Sellix, Michael T.', 'Rahman, Irfan']",Sci Rep,,,True
ae6773868c2850e5c8b8177735b19d01341a53b6,PMC,Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD,http://dx.doi.org/10.1038/srep09927,PMC4413879,25923474,CC BY,"Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations.",2015 Apr 29,"['Sundar, Isaac K.', 'Ahmad, Tanveer', 'Yao, Hongwei', 'Hwang, Jae-woong', 'Gerloff, Janice', 'Lawrence, B. Paige', 'Sellix, Michael T.', 'Rahman, Irfan']",Sci Rep,,,False
98e35a687137cb2b91458118347ad93f7ad188fb,PMC,A Human Monoclonal Antibody against Hepatitis B Surface Antigen with Potent Neutralizing Activity,http://dx.doi.org/10.1371/journal.pone.0125704,PMC4414269,25923526,CC BY,"We describe the production and characterization of human monoclonal antibodies (mAb) specific for the major hepatitis B virus (HBV) S protein. The mAbs, two IgG1κ and one IgG1λ, were secreted by B-cell clones obtained from peripheral blood mononuclear cells (PBMC) of one person convalescent from acute hepatitis B and one vaccinated individual. The former recognized a denaturation-insensitive epitope within the p24 protein whereas the latter recognized a denaturation-sensitive, conformational epitope located within the HBsAg common “a” determinant. This mAb, denominated ADRI-2F3, displayed a very high protective titer of over 43,000 IU/mg mAb and showed an extremely potent neutralizing activity in the in vitro model of HBV infection using primary hepatocytes from Tupaia belangeri as target. Recombinant variable heavy and light domain sequences derived from mAb ADRI-2F3 were cloned into eukaryotic expression vectors and showed identical fine specificity and 1 log(10) higher titer than the original IgG1λ. It is envisaged that such mAb will be able to efficiently prevent HBV reinfection after liver transplantation for end-stage chronic HBV infection or infection after needle-stick exposure, providing an unlimited source of valuable protective anti-HBs antibody.",2015 Apr 29,"['Cerino, Antonella', 'Bremer, Corinna M.', 'Glebe, Dieter', 'Mondelli, Mario U.']",PLoS One,,,True
bc558b5af5c0e23264cc177d3c0622a8726deb2e,PMC,Resolution of the cellular proteome of the nucleocapsid protein from a highly pathogenic isolate of porcine reproductive and respiratory syndrome virus identifies PARP-1 as a cellular target whose interaction is critical for virus biology,http://dx.doi.org/10.1016/j.vetmic.2014.11.023,PMC4414928,25614100,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to the swine industry and food security worldwide. The nucleocapsid (N) protein is a major structural protein of PRRSV. The primary function of this protein is to encapsidate the viral RNA genome, and it is also thought to participate in the modulation of host cell biology and recruitment of cellular factors to facilitate virus infection. In order to the better understand these latter roles the cellular interactome of PRRSV N protein was defined using label free quantitative proteomics. This identified several cellular factors that could interact with the N protein including poly [ADP-ribose] polymerase 1 (PARP-1), a cellular protein, which can add adenosine diphosphate ribose to a protein. Use of the PARP-1 small molecule inhibitor, 3-AB, in PRRSV infected cells demonstrated that PARP-1 was required and acted as an enhancer factor for virus biology. Serial growth of PRRSV in different concentrations of 3-AB did not yield viruses that were able to grow with wild type kinetics, suggesting that by targeting a cellular protein crucial for virus biology, resistant phenotypes did not emerge. This study provides further evidence that cellular proteins, which are critical for virus biology, can also be targeted to ablate virus growth and provide a high barrier for the emergence of drug resistance.",2015 Mar 23,"['Liu, Long', 'Lear, Zoe', 'Hughes, David J.', 'Wu, Weining', 'Zhou, En-min', 'Whitehouse, Adrian', 'Chen, Hongying', 'Hiscox, Julian A.']",Vet Microbiol,,,False
57175f1b43951c500b3fe6cb678824ea9e6d8ae2,PMC,The evidence base of primary research in public health emergency preparedness: a scoping review and stakeholder consultation,http://dx.doi.org/10.1186/s12889-015-1750-1,PMC4415223,25925775,CC BY,"BACKGROUND: Effective public health emergency preparedness and response systems are important in mitigating the impact of all-hazards emergencies on population health. The evidence base for public health emergency preparedness (PHEP) is weak, however, and previous reviews have noted a substantial proportion of anecdotal event reports. To investigate the body of research excluding the anecdotal reports and better understand primary and analytical research for PHEP, a scoping review was conducted with two objectives: first, to develop a thematic map focused on primary research; and second, to use this map to inform and guide an understanding of knowledge gaps relevant to research and practice in PHEP. METHODS: A scoping review was conducted based on established methodology. Multiple databases of indexed and grey literature were searched based on concepts of public health, emergency, emergency management/preparedness and evaluation/evidence. Inclusion and exclusion criteria were applied iteratively. Primary research studies that were evidence-based or evaluative in nature were included in the final group of selected studies. Thematic analysis was conducted for this group. Stakeholder consultation was undertaken for the purpose of validating themes and identifying knowledge gaps. To accomplish this, a purposive sample of researchers and practicing professionals in PHEP or closely related fields was asked to complete an online survey and participate in an in-person meeting. Final themes and knowledge gaps were synthesized after stakeholder consultation. RESULTS: Database searching yielded 3015 citations and article selection resulted in a final group of 58 articles. A list of ten themes from this group of articles was disseminated to stakeholders with the survey questions. Survey findings resulted in four cross-cutting themes and twelve stand-alone themes. Several key knowledge gaps were identified in the following themes: attitudes and beliefs; collaboration and system integration; communication; quality improvement and performance standards; and resilience. Resilience emerged as both a gap and a cross-cutting theme. Additional cross-cutting themes included equity, gender considerations, and high risk or at-risk populations. CONCLUSIONS: In this scoping review of the literature enhanced by stakeholder consultation, key themes and knowledge gaps in the PHEP evidence base were identified which can be used to inform future practice-oriented research in PHEP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1750-1) contains supplementary material, which is available to authorized users.",2015 Apr 28,"['Khan, Yasmin', 'Fazli, Ghazal', 'Henry, Bonnie', 'de Villa, Eileen', 'Tsamis, Charoula', 'Grant, Moira', 'Schwartz, Brian']",BMC Public Health,,,True
d15dcc8f6d6ca39f7d43a8673ba44b0f0c53e449,PMC,From the Editor's desk,http://dx.doi.org/10.1111/irv.12311,PMC4415693,25824028,CC BY,,2015 May 23,"Nguyen-Van-Tam, Jonathan S",Influenza Other Respir Viruses,,,True
8cf5055e0ca001204109a5455b58a42aaa79f431,PMC,Healthcare workers' willingness to work during an influenza pandemic: a systematic review and meta-analysis,http://dx.doi.org/10.1111/irv.12310,PMC4415696,25807865,CC BY,"To estimate the proportion of healthcare workers (HCWs) willing to work during an influenza pandemic and identify associated risk factors, we undertook a systematic review and meta-analysis compliant with PRISMA guidance. Databases and grey literature were searched to April 2013, and records were screened against protocol eligibility criteria. Data extraction and risk of bias assessments were undertaken using a piloted form. Random-effects meta-analyses estimated (i) pooled proportion of HCWs willing to work and (ii) pooled odds ratios of risk factors associated with willingness to work. Heterogeneity was quantified using the I(2) statistic, and publication bias was assessed using funnel plots and Egger's test. Data were synthesized narratively where meta-analyses were not possible. Forty-three studies met our inclusion criteria. Meta-analysis of the proportion of HCWs willing to work was abandoned due to excessive heterogeneity (I(2) = 99·2%). Narrative synthesis showed study estimates ranged from 23·1% to 95·8% willingness to work, depending on context. Meta-analyses of specific factors showed that male HCWs, physicians and nurses, full-time employment, perceived personal safety, awareness of pandemic risk and clinical knowledge of influenza pandemics, role-specific knowledge, pandemic response training, and confidence in personal skills were statistically significantly associated with increased willingness. Childcare obligations were significantly associated with decreased willingness. HCWs' willingness to work during an influenza pandemic was moderately high, albeit highly variable. Numerous risk factors showed a statistically significant association with willingness to work despite significant heterogeneity between studies. None of the included studies were based on appropriate theoretical constructs of population behaviour.",2015 May 23,"['Aoyagi, Yumiko', 'Beck, Charles R', 'Dingwall, Robert', 'Nguyen-Van-Tam, Jonathan S']",Influenza Other Respir Viruses,,,True
fd31ade73c720f893a5ddb2370df90a84511ec4a,PMC,"Distribution of antibodies against influenza virus in pigs from farrow-to-finish farms in Minas Gerais state, Brazil",http://dx.doi.org/10.1111/irv.12304,PMC4415701,25648743,CC BY,"BACKGROUND: Swine influenza virus (SIV) is the cause of an acute respiratory disease that affects swine worldwide. In Brazil, SIV has been identified in pigs since 1978. After the emergence of pandemic H1N1 in 2009 (H1N1pdm09), few studies reported the presence of influenza virus in Brazilian herds. OBJECTIVES: The objective of this study was to evaluate the serological profile for influenza virus in farrow-to-finish pig farms in Minas Gerais state, Brazil. METHODS: Thirty farms with no SIV vaccination history were selected from the four larger pig production areas in Minas Gerais state (Zona da Mata, Triângulo Mineiro/Alto Paranaíba, South/Southwest and the Belo Horizonte metropolitan area). At each farm, blood samples were randomly collected from 20 animals in each production cycle category: breeding animals (sows and gilts), farrowing crate (2–3 weeks), nursery (4–7 weeks), grower pigs (8–14 weeks), and finishing pigs (15–16 weeks), with 100 samples per farm and a total of 3000 animals in this study. The samples were tested for hemagglutination inhibition activity against H1N1 pandemic strain (A/swine/Brazil/11/2009) and H3N2 SIV (A/swine/Iowa/8548-2/98) reference strain. RESULTS: The percentages of seropositive animals for H1N1pdm09 and H3N2 were 26·23% and 1·57%, respectively, and the percentages of seropositive herds for both viruses were 96·6% and 13·2%, respectively. CONCLUSIONS: The serological profiles differed for both viruses and among the studied areas, suggesting a high variety of virus circulation around the state, as well as the presence of seronegative animals susceptible to influenza infection and, consequently, new respiratory disease outbreaks.",2015 May 23,"['Dias, Alessandra S', 'Costa, Érica A', 'Rajão, Daniela S', 'Guedes, Roberto M C', 'Ciacci Zanella, Janice R', 'Lobato, Zélia I P']",Influenza Other Respir Viruses,,,True
2bf3f075175c307923fc400707b30616a676419c,PMC,The Ubiquitin Proteasome System Plays a Role in Venezuelan Equine Encephalitis Virus Infection,http://dx.doi.org/10.1371/journal.pone.0124792,PMC4415917,25927990,CC BY,"Many viruses have been implicated in utilizing or modulating the Ubiquitin Proteasome System (UPS) to enhance viral multiplication and/or to sustain a persistent infection. The mosquito-borne Venezuelan equine encephalitis virus (VEEV) belongs to the Togaviridae family and is an important biodefense pathogen and select agent. There are currently no approved vaccines or therapies for VEEV infections; therefore, it is imperative to identify novel targets for therapeutic development. We hypothesized that a functional UPS is required for efficient VEEV multiplication. We have shown that at non-toxic concentrations Bortezomib, a FDA-approved inhibitor of the proteasome, proved to be a potent inhibitor of VEEV multiplication in the human astrocytoma cell line U87MG. Bortezomib inhibited the virulent Trinidad donkey (TrD) strain and the attenuated TC-83 strain of VEEV. Additional studies with virulent strains of Eastern equine encephalitis virus (EEEV) and Western equine encephalitis virus (WEEV) demonstrated that Bortezomib is a broad spectrum inhibitor of the New World alphaviruses. Time-of-addition assays showed that Bortezomib was an effective inhibitor of viral multiplication even when the drug was introduced many hours post exposure to the virus. Mass spectrometry analyses indicated that the VEEV capsid protein is ubiquitinated in infected cells, which was validated by confocal microscopy and immunoprecipitation assays. Subsequent studies revealed that capsid is ubiquitinated on K48 during early stages of infection which was affected by Bortezomib treatment. This study will aid future investigations in identifying host proteins as potential broad spectrum therapeutic targets for treating alphavirus infections.",2015 Apr 30,"['Amaya, Moushimi', 'Keck, Forrest', 'Lindquist, Michael', 'Voss, Kelsey', 'Scavone, Lauren', 'Kehn-Hall, Kylene', 'Roberts, Brian', 'Bailey, Charles', 'Schmaljohn, Connie', 'Narayanan, Aarthi']",PLoS One,,,True
3025f11897040ad8046b2a7ef8e94fc8615df214,PMC,"Impact of the 2009 H1N1 Pandemic on Age-Specific Epidemic Curves of Other Respiratory Viruses: A Comparison of Pre-Pandemic, Pandemic and Post-Pandemic Periods in a Subtropical City",http://dx.doi.org/10.1371/journal.pone.0125447,PMC4416050,25928217,CC BY,"BACKGROUND: The 2009 H1N1 influenza pandemic caused offseason peaks in temperate regions but coincided with the summer epidemic of seasonal influenza and other common respiratory viruses in subtropical Hong Kong. This study was aimed to investigate the impact of the pandemic on age-specific epidemic curves of other respiratory viruses. METHODS: Weekly laboratory-confirmed cases of influenza A (subtypes seasonal A(H1N1), A(H3N2), pandemic virus A(H1N1)pdm09), influenza B, respiratory syncytial virus (RSV), adenovirus and parainfluenza were obtained from 2004 to 2013. Age-specific epidemic curves of viruses other than A(H1N1)pdm09 were compared between the pre-pandemic (May 2004 – April 2009), pandemic (May 2009 – April 2010) and post-pandemic periods (May 2010 – April 2013). RESULTS: There were two peaks of A(H1N1)pdm09 in Hong Kong, the first in September 2009 and the second in February 2011. The infection rate was found highest in young children in both waves, but markedly fewer cases in school children were recorded in the second wave than in the first wave. Positive proportions of viruses other than A(H1N1)pdm09 markedly decreased in all age groups during the first pandemic wave. After the first wave of the pandemic, the positive proportion of A(H3N2) increased, but those of B and RSV remained slightly lower than their pre-pandemic proportions. Changes in seasonal pattern and epidemic peak time were also observed, but inconsistent across virus-age groups. CONCLUSION: Our findings provide some evidence that age distribution, seasonal pattern and peak time of other respiratory viruses have changed since the pandemic. These changes could be the result of immune interference and changing health seeking behavior, but the mechanism behind still needs further investigations.",2015 Apr 30,"['Yang, Lin', 'Chan, Kwok Hung', 'Suen, Lorna K. P.', 'Chan, King Pan', 'Wang, Xiling', 'Cao, Peihua', 'He, Daihai', 'Peiris, J. S. Malik', 'Wong, Chit Ming']",PLoS One,,,True
bc67c021d6e189215a0101f6e5de32daa8e4ccee,PMC,Diversity of coronavirus in bats from Eastern Thailand,http://dx.doi.org/10.1186/s12985-015-0289-1,PMC4416284,25884446,CC BY,"BACKGROUND: Bats are reservoirs for a diverse range of coronaviruses (CoVs), including those closely related to human pathogens such as Severe Acute Respiratory Syndrome (SARS) CoV and Middle East Respiratory Syndrome CoV. There are approximately 139 bat species reported to date in Thailand, of which two are endemic species. Due to the zoonotic potential of CoVs, standardized surveillance efforts to characterize viral diversity in wildlife are imperative. FINDINGS: A total of 626 bats from 19 different bat species were individually sampled from 5 provinces in Eastern Thailand between 2008 and 2013 (84 fecal and 542 rectal swabs). Samples collected (either fresh feces or rectal swabs) were placed directly into RNA stabilization reagent, transported on ice within 24 hours and preserved at −80°C until further analysis. CoV RNA was detected in 47 specimens (7.6%), from 13 different bat species, using broadly reactive consensus PCR primers targeting the RNA-Dependent RNA Polymerase gene designed to detect all CoVs. Thirty seven alphacoronaviruses, nine lineage D betacoronaviruses, and one lineage B betacoronavirus (SARS-CoV related) were identified. Six new bat CoV reservoirs were identified in our study, namely Cynopterus sphinx, Taphozous melanopogon, Hipposideros lekaguli, Rhinolophus shameli, Scotophilus heathii and Megaderma lyra. CONCLUSIONS: CoVs from the same genetic lineage were found in different bat species roosting in similar or different locations. These data suggest that bat CoV lineages are not strictly concordant with their hosts. Our phylogenetic data indicates high diversity and a complex ecology of CoVs in bats sampled from specific areas in eastern regions of Thailand. Further characterization of additional CoV genes may be useful to better describe the CoV divergence.",2015 Apr 11,"['Wacharapluesadee, Supaporn', 'Duengkae, Prateep', 'Rodpan, Apaporn', 'Kaewpom, Thongchai', 'Maneeorn, Patarapol', 'Kanchanasaka, Budsabong', 'Yingsakmongkon, Sangchai', 'Sittidetboripat, Nuntaporn', 'Chareesaen, Chaiyaporn', 'Khlangsap, Nathawat', 'Pidthong, Apisit', 'Leadprathom, Kumron', 'Ghai, Siriporn', 'Epstein, Jonathan H', 'Daszak, Peter', 'Olival, Kevin J', 'Blair, Patrick J', 'Callahan, Michael V', 'Hemachudha, Thiravat']",Virol J,,,True
27636c830ab9c45d38454d50312227747652f70e,PMC,Differential expression of miRNAs in enterovirus 71-infected cells,http://dx.doi.org/10.1186/s12985-015-0288-2,PMC4416288,25889836,CC BY,"BACKGROUND: Enterovirus 71 (EV71) is one of the major etiological pathogens of hand, foot and mouth disease (HFMD) and can cause severe cerebral and pulmonary complications and even fatality. MicroRNAs (miRNAs), a class of small non-coding RNA molecules, play an important role in post-transcriptional regulation of gene expression and thereby influencing various physiological and pathological processes. Increasing evidence suggests that miRNAs act as key effector molecules in the complicated pathogen-host interactions. However, the roles of miRNAs in EV71 infection and pathogenesis are not well understood. METHODS: To identify special miRNAs involved in EV71 infection, a microarray assay was performed to study the expression pattern of miRNAs in EV71-infected human rhabdomyosarcoma cells (RD cells) and uninfected RD cells. We further predicted the putative target genes for the dysregulated miRNAs using the online bioinformatic algorithms (TargetScan, miRanda and PicTar) and carried out functional annotation including GO enrichment and KEGG pathway analysis for miRNA predicted targets. Then, the results of microarray were further confirmed by quantitative RT-PCR. RESULTS: Totally, 45 differentially expressed miRNAs ware identified by microarray, among which 36 miRNAs were up-regulated and 9 were down-regulated. 7166 predicted target genes for the dysregulated miRNAs were revealed by using TargetScan in conjunction with miRanda and PicTar. The GO annotation suggested that predicted targets of miRNAs were enriched into the category of signal transduction, regulation of transcription, metabolic process, protein phosphorylation, apoptotic process and immune response. KEGG pathway analysis suggested that these predicted target genes were involved in many important pathways, mainly including endocytosis and focal adhesion, MAPK signaling pathway, hypertrophic cardiomyopathy, melanogenesis and ErbB signaling pathway. The expression levels of 8 most differentially up-regulated miRNAs and 3 most differentially down-regulated miRNAs were confirmed by qRT-PCR. The expressions of hsa-miR-4530, hsa-miR-4492, hsa-miR-6125, hsa-miR-494-3p, hsa-miR-638, hsa-miR-6743-5p, hsa-miR-4459 and hsa-miR-4443 detected by qRT-PCR were consistent with the microarray data. CONCLUSION: These results might extend our understanding to the regulatory mechanism of miRNAs underlying the pathogenesis of EV71 infection, thus strengthening the preventative and therapeutic strategies of HFMD caused by EV71.",2015 Apr 10,"['Xun, Meng', 'Ma, Chao-Feng', 'Du, Quan-Li', 'Ji, Yan-Hong', 'Xu, Ji-Ru']",Virol J,,,True
87620b2fa94ff9b59a3a84382dceae62f83259a6,PMC,Postnatal Persistent Infection with Classical Swine Fever Virus and Its Immunological Implications,http://dx.doi.org/10.1371/journal.pone.0125692,PMC4418595,25938664,CC BY,"It is well established that trans-placental transmission of classical swine fever virus (CSFV) during mid-gestation can lead to persistently infected offspring. The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection. Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively. During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum. Importantly, these animals were unable to mount any detectable humoral and cellular immune response. At necropsy, the most prominent gross pathological lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN-γ-producing cells. These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs. However, IL-10 was undetectable in the sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs from the persistently infected piglets produced IL-10. Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN-γ producing cells was not restored. Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets. Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet. Since serological methods are routinely used in CSFV surveillance, persistently infected pigs might go unnoticed. In addition to the epidemiological and economic significance of persistent CSFV infection, this model could be useful for understanding the mechanisms of viral persistence.",2015 May 4,"['Muñoz-González, Sara', 'Ruggli, Nicolas', 'Rosell, Rosa', 'Pérez, Lester Josué', 'Frías-Leuporeau, Maria Teresa', 'Fraile, Lorenzo', 'Montoya, Maria', 'Cordoba, Lorena', 'Domingo, Mariano', 'Ehrensperger, Felix', 'Summerfield, Artur', 'Ganges, Llilianne']",PLoS One,,,True
9c930b820306b68f83b4706c10aae46bf2ed70b7,PMC,Evaluation of porcine epidemic diarrhea virus transmission and the immune response in growing pigs,http://dx.doi.org/10.1186/s13567-015-0180-5,PMC4419466,25943434,CC BY,"Clinical disease associated with porcine epidemic diarrhea virus (PEDV) infection in naïve pigs is well chronicled; however, information on endemic PEDV infection is limited. To characterize chronic PEDV infection, the duration of infectious virus shedding and development of protective immunity was determined. On Day 0 (D0), a growing pig was challenged with PEDV and 13 contacts were commingled. On D7, 9 contact pigs (principal virus group (PG)), were selected, moved to a separate room and commingled with one sentinel pig (S1). This process was repeated weekly with S2, S3 and S4. The PG was PEDV-positive by PCR from D3-11, with some pigs intermittently positive to D42. Pigs S1 and S2 were PEDV-positive within 24 hours of commingling. Antibodies were detected in all PG by D21 and by 7 days post-contact in S1 and S2. Pigs S3 and S4 were PCR and antibody negative following commingling. To evaluate protective immunity, 5 naïve pigs (N) and the PG were challenged (N/C, PG/C) with homologous virus on D49. All N/C pigs were PEDV PCR-positive by D52 with detection out to D62 in 3/5 N/C pigs. All PG/C pigs were PEDV PCR-negative post-challenge. By D63, all N/C seroconverted. Although PEDV RNA was demonstrated in pigs after primary infection until D42, infectious PEDV capable of horizontal transmission to naïve pigs was only shed 14–16 days after infection to age-matched pigs. Homologous re-challenge 49 days post initial PEDV exposure did not result in re-infection of the pigs. This demonstrates potential for an effective PEDV vaccine.",2015 May 6,"['Crawford, Kimberly', 'Lager, Kelly', 'Miller, Laura', 'Opriessnig, Tanja', 'Gerber, Priscilla', 'Hesse, Richard']",Vet Res,,,True
ebac83e8603fe1bfb0091c0733f9a10c95208599,PMC,Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis,http://dx.doi.org/10.1186/s12879-015-0938-4,PMC4419503,25928122,CC BY,"BACKGROUND: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis. METHODS: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex™) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it™). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity. RESULTS: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results. CONCLUSIONS: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0938-4) contains supplementary material, which is available to authorized users.",2015 Apr 28,"['Ljungström, Lars', 'Enroth, Helena', 'Claesson, Berndt EB', 'Ovemyr, Ida', 'Karlsson, Jesper', 'Fröberg, Berit', 'Brodin, Anna-Karin', 'Pernestig, Anna-Karin', 'Jacobsson, Gunnar', 'Andersson, Rune', 'Karlsson, Diana']",BMC Infect Dis,,,False
c3a82cf68990138f6cbbbfe60b5b80d3f6d2e260,PMC,Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis,http://dx.doi.org/10.1186/s12879-015-0938-4,PMC4419503,25928122,CC BY,"BACKGROUND: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis. METHODS: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex™) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it™). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity. RESULTS: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results. CONCLUSIONS: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0938-4) contains supplementary material, which is available to authorized users.",2015 Apr 28,"['Ljungström, Lars', 'Enroth, Helena', 'Claesson, Berndt EB', 'Ovemyr, Ida', 'Karlsson, Jesper', 'Fröberg, Berit', 'Brodin, Anna-Karin', 'Pernestig, Anna-Karin', 'Jacobsson, Gunnar', 'Andersson, Rune', 'Karlsson, Diana']",BMC Infect Dis,,,True
d17a476d549a21be3e70932a10c6fef328f42ba6,PMC,Griffithsin tandemers: flexible and potent lectin inhibitors of the human immunodeficiency virus,http://dx.doi.org/10.1186/s12977-014-0127-3,PMC4419512,25613831,CC BY,"BACKGROUND: The lectin griffithsin (GRFT) is a potent antiviral agent capable of prevention and treatment of infections caused by a number of enveloped viruses and is currently under development as an anti-HIV microbicide. In addition to its broad antiviral activity, GRFT is stable at high temperature and at a broad pH range, displays little toxicity and immunogenicity, and is amenable to large-scale manufacturing. Native GRFT is a domain-swapped homodimer that binds to viral envelope glycoproteins and has displayed mid-picomolar activity in cell-based anti-HIV assays. Previously, we have engineered and analyzed several monomeric forms of this lectin (mGRFT) with anti-HIV EC(50) values ranging up to 323 nM. Based on our previous analysis of mGRFT, we hypothesized that the orientation and spacing of the carbohydrate binding domains GRFT were key to its antiviral activity. RESULTS: Here we present data on engineered tandem repeats of mGRFT (mGRFT tandemers) with antiviral activity at concentrations as low as one picomolar in whole-cell anti-HIV assays. mGRFT tandemers were analyzed thermodynamically, both individually and in complex with HIV-1 gp120. We also demonstrate by dynamic light scattering and cryo-electron microscopy that mGRFT tandemers do not aggregate HIV virions. This establishes that, although the intra-virion crosslinking of HIV envelope glycoproteins is likely integral to their activity, the antiviral activity of these lectins is not due to virus aggregation caused by inter-virion crosslinking. CONCLUSIONS: The engineered tandemer constructs of mGRFT may provide novel and powerful agents for prevention of infection by HIV and other enveloped viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-014-0127-3) contains supplementary material, which is available to authorized users.",2015 Jan 23,"['Moulaei, Tinoush', 'Alexandre, Kabamba B', 'Shenoy, Shilpa R', 'Meyerson, Joel R', 'Krumpe, Lauren RH', 'Constantine, Brian', 'Wilson, Jennifer', 'Buckheit, Robert W', 'McMahon, James B', 'Subramaniam, Sriram', 'Wlodawer, Alexander', 'O’Keefe, Barry R']",Retrovirology,,,True
34f0507e2d36312bb0a90c6c9a66acd14d9154c3,PMC,OASes and STING: Adaptive Evolution in Concert,http://dx.doi.org/10.1093/gbe/evv046,PMC4419793,25752600,CC BY,"OAS (2′–5′-oligoadenylate synthases) proteins and cyclic GMP–AMP synthase (cGAS, gene symbol: MB21D1) patrol the cytoplasm for the presence of foreign nucleic acids. Upon binding to double-stranded RNA or double-stranded DNA, OAS proteins and cGAS produce nucleotide second messengers to activate RNase L and STING (stimulator of interferon genes, gene symbol: TMEM173), respectively; this leads to the initiation of antiviral responses. We analyzed the evolutionary history of the MB21D1–TMEM173 and OAS–RNASEL axes in primates and bats and found evidence of widespread positive selection in both orders. In TMEM173, residue 230, a major determinant of response to natural ligands and to mimetic drugs (e.g., DMXAA), was positively selected in Primates and Chiroptera. In both orders, selection also targeted an α-helix/loop element in RNase L that modulates the enzyme preference for single-stranded RNA versus stem loops. Analysis of positively selected sites in OAS1, OAS2, and MB21D1 revealed parallel evolution, with the corresponding residues being selected in different genes. As this cannot result from gene conversion, these data suggest that selective pressure acting on OAS and MB21D1 genes is related to nucleic acid recognition and to the specific mechanism of enzyme activation, which requires a conformational change. Finally, a population genetics-phylogenetics analysis in humans, chimpanzees, and gorillas detected several positively selected sites in most genes. Data herein shed light into species-specific differences in infection susceptibility and in response to synthetic compounds, with relevance for the design of synthetic compounds as vaccine adjuvants.",2015 Mar 9,"['Mozzi, Alessandra', 'Pontremoli, Chiara', 'Forni, Diego', 'Clerici, Mario', 'Pozzoli, Uberto', 'Bresolin, Nereo', 'Cagliani, Rachele', 'Sironi, Manuela']",Genome Biol Evol,,,True
526b8ff2051f296de62ce8ceccc0d384c2e68c6a,PMC,OASes and STING: Adaptive Evolution in Concert,http://dx.doi.org/10.1093/gbe/evv046,PMC4419793,25752600,CC BY,"OAS (2′–5′-oligoadenylate synthases) proteins and cyclic GMP–AMP synthase (cGAS, gene symbol: MB21D1) patrol the cytoplasm for the presence of foreign nucleic acids. Upon binding to double-stranded RNA or double-stranded DNA, OAS proteins and cGAS produce nucleotide second messengers to activate RNase L and STING (stimulator of interferon genes, gene symbol: TMEM173), respectively; this leads to the initiation of antiviral responses. We analyzed the evolutionary history of the MB21D1–TMEM173 and OAS–RNASEL axes in primates and bats and found evidence of widespread positive selection in both orders. In TMEM173, residue 230, a major determinant of response to natural ligands and to mimetic drugs (e.g., DMXAA), was positively selected in Primates and Chiroptera. In both orders, selection also targeted an α-helix/loop element in RNase L that modulates the enzyme preference for single-stranded RNA versus stem loops. Analysis of positively selected sites in OAS1, OAS2, and MB21D1 revealed parallel evolution, with the corresponding residues being selected in different genes. As this cannot result from gene conversion, these data suggest that selective pressure acting on OAS and MB21D1 genes is related to nucleic acid recognition and to the specific mechanism of enzyme activation, which requires a conformational change. Finally, a population genetics-phylogenetics analysis in humans, chimpanzees, and gorillas detected several positively selected sites in most genes. Data herein shed light into species-specific differences in infection susceptibility and in response to synthetic compounds, with relevance for the design of synthetic compounds as vaccine adjuvants.",2015 Mar 9,"['Mozzi, Alessandra', 'Pontremoli, Chiara', 'Forni, Diego', 'Clerici, Mario', 'Pozzoli, Uberto', 'Bresolin, Nereo', 'Cagliani, Rachele', 'Sironi, Manuela']",Genome Biol Evol,,,False
eb0d926b1fa6dc7d9f86a001f8ccd69407c5ed86,PMC,Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape,http://dx.doi.org/10.1371/journal.pgen.1005203,PMC4420275,25942676,CC BY,"A diverse subset of pattern recognition receptors (PRRs) detects pathogen-associated nucleic acids to initiate crucial innate immune responses in host organisms. Reflecting their importance for host defense, pathogens encode various countermeasures to evade or inhibit these immune effectors. PRRs directly engaged by pathogen inhibitors often evolve under recurrent bouts of positive selection that have been described as molecular ‘arms races.’ Cyclic GMP-AMP synthase (cGAS) was recently identified as a key PRR. Upon binding cytoplasmic double-stranded DNA (dsDNA) from various viruses, cGAS generates the small nucleotide secondary messenger cGAMP to signal activation of innate defenses. Here we report an evolutionary history of cGAS with recurrent positive selection in the primate lineage. Recent studies indicate a high degree of structural similarity between cGAS and 2’-5’-oligoadenylate synthase 1 (OAS1), a PRR that detects double-stranded RNA (dsRNA), despite low sequence identity between the respective genes. We present comprehensive comparative evolutionary analysis of cGAS and OAS1 primate sequences and observe positive selection at nucleic acid binding interfaces and distributed throughout both genes. Our data revealed homologous regions with strong signatures of positive selection, suggesting common mechanisms employed by unknown pathogen encoded inhibitors and similar modes of evasion from antagonism. Our analysis of cGAS diversification also identified alternately spliced forms missing multiple sites under positive selection. Further analysis of selection on the OAS family in primates, which comprises OAS1, OAS2, OAS3 and OASL, suggests a hypothesis where gene duplications and domain fusion events result in paralogs that provide another means of escaping pathogen inhibitors. Together our comparative evolutionary analysis of cGAS and OAS provides new insights into distinct mechanisms by which key molecular sentinels of the innate immune system have adapted to circumvent viral-encoded inhibitors.",2015 May 5,"['Hancks, Dustin C.', 'Hartley, Melissa K.', 'Hagan, Celia', 'Clark, Nathan L.', 'Elde, Nels C.']",PLoS Genet,,,True
396312dfae0562afce275a99e96c903e91aa96c9,PMC,Interferon-Inducible Transmembrane Protein 3 Genetic Variant rs12252 and Influenza Susceptibility and Severity: A Meta-Analysis,http://dx.doi.org/10.1371/journal.pone.0124985,PMC4420464,25942469,CC BY,"BACKGROUND: The pandemic influenza A (H1N1) pdm09 virus, avian influenza A (H5N1) virus, and influenza A (H7N9) virus induced severe morbidity and mortality throughout the world. Previous studies suggested a close association between the interferon-induced transmembrane protein-3 (IFITM3) genetic variant rs12252 and influenza. Here, we explored the correlation between the rs12252 and influenza susceptibility and severity using meta-analysis. METHODS: Relevant studies published before May 22, 2014 were retrieved from PubMed, ISI web of knowledge, EBSCO, and Cochrane central register of controlled trials databases. Association between rs12252 and influenza susceptibility and severity were determined using statistical analysis of odds ratios (ORs). RESULTS: A total of four studies consisting of 445 cases and 4180 controls were included in our analysis. Generally, there is increased risk of influenza in subjects carrying rs12252 in the recessive model (CC vs. CT+TT: OR = 2.35, 95% CI: 1.49-3.70, P<0.001), the dominant model (CC+CT vs. TT: OR=1.60, 95% CI: 1.18–2.22, P=0.003), the homozygote comparison (CC vs. TT: OR=4.11, 95% CI: 2.15–7.84, P<0.001), and the allele contrast (C vs. T: OR=1.67, 95% CI: 1.32–2.13, P<0.001). Stratification analysis of ethnicity and severity revealed a significant increase in influenza susceptibility by IFITM3-SNP rs12252 among both Asian and Caucasian population. SNP rs12252 shows significant impact on severe infections (P<0.05), but not on mild influenza. Besides, our result also associated rs12252 with influenza severity (severe vs. mild: OR=2.37, 95% CI: 1.32–4.25, P=0.004), (severe vs. control: OR=2.70, 95% CI: 1.85–3.94, P<0.001). CONCLUSION: Our meta-analysis suggests a significant association between a minor IFITM3 allele (SNP rs12252-C) with severe influenza susceptibility, but not in mild influenza subjects, in both UK Caucasians and Han Chinese population. The rs12252-C allele causes a 23.7% higher chance of infection and also constitutes a risk factor for more severe influenza.",2015 May 5,"['Yang, Xianxian', 'Tan, Bin', 'Zhou, Xipeng', 'Xue, Jian', 'Zhang, Xian', 'Wang, Peng', 'Shao, Chuang', 'Li, Yingli', 'Li, Chaorui', 'Xia, Huiming', 'Qiu, Jingfu']",PLoS One,,,True
6bfa66e7befc8ca735ef61dc392a32d1c56ea01e,PMC,Perturbations at the ribosomal genes loci are at the centre of cellular dysfunction and human disease,http://dx.doi.org/10.1186/2045-3701-4-43,PMC4422213,25949792,CC BY,"Ribosomal RNA (rRNA) gene (rDNA) transcription by RNA Polymerase I (Pol I) drives cell growth and underlies nucleolar structure and function, indirectly coordinating many fundamental cellular processes. The importance of keeping rDNA transcription under tight control is reflected by the fact that deranged Pol I transcription is a feature of cancer and other human disorders. In this review, we discuss multiple aspects of rDNA function including the relationship between Pol I transcription and proliferative capacity, the role of Pol I transcription in mediating nucleolar structure and integrity, and rDNA/nucleolar interactions with the genome and their influence on heterochromatin and global genome stability. Furthermore, we discuss how perturbations in the structure of the rDNA loci might contribute to human disease, in some cases independent of effects on ribosome biogenesis.",2014 Aug 19,"['Diesch, Jeannine', 'Hannan, Ross D', 'Sanij, Elaine']",Cell Biosci,,,True
215fb42f8f5f2ede1ed7e7b1561e51f494593578,PMC,Modulation of angiotensin II signaling in the prevention of fibrosis,http://dx.doi.org/10.1186/s13069-015-0023-z,PMC4422447,25949522,CC BY,"Over the last decade, it has become clear that the role of angiotensin II extends far beyond recognized renal and cardiovascular effects. The presence of an autologous renin-angiotensin system has been demonstrated in almost all tissues of the body. It is now known that angiotensin II acts both independently and in synergy with TGF-beta to induce fibrosis via the angiotensin type 1 receptor (AT(1)) in a multitude of tissues outside of the cardiovascular and renal systems, including pulmonary fibrosis, intra-abdominal fibrosis, and systemic sclerosis. Interestingly, recent studies have described a paradoxically regenerative effect of the angiotensin system via stimulation of the angiotensin type 2 receptor (AT(2)). Activation of AT(2) has been shown to ameliorate fibrosis in animal models of skeletal muscle, gastrointestinal, and neurologic diseases. Clinical reports suggest a beneficial role for modulation of angiotensin II signaling in cutaneous scarring. This article reviews current knowledge on the role that angiotensin II plays in tissue fibrosis, as well as current and potential therapies targeting this system.",2015 Apr 23,"['Murphy, Amanda M', 'Wong, Alison L', 'Bezuhly, Michael']",Fibrogenesis Tissue Repair,,,True
c2986eb912dbecc9c8508361012392706955076e,PMC,Viroporin Activity of the Foot-and-Mouth Disease Virus Non-Structural 2B Protein,http://dx.doi.org/10.1371/journal.pone.0125828,PMC4422707,25946195,CC BY,"Viroporins are a family of low-molecular-weight hydrophobic transmembrane proteins that are encoded by various animal viruses. Viroporins form transmembrane pores in host cells via oligomerization, thereby destroying cellular homeostasis and inducing cytopathy for virus replication and virion release. Among the Picornaviridae family of viruses, the 2B protein encoded by enteroviruses is well understood, whereas the viroporin activity of the 2B protein encoded by the foot-and-mouth disease virus (FMDV) has not yet been described. An analysis of the FMDV 2B protein domains by computer-aided programs conducted in this study revealed that this protein may contain two transmembrane regions. Further biochemical, biophysical and functional studies revealed that the protein possesses a number of features typical of a viroporin when it is overexpressed in bacterial and mammalian cells as well as in FMDV-infected cells. The protein was found to be mainly localized in the endoplasmic reticulum (ER), with both the N- and C-terminal domains stretched into the cytosol. It exhibited cytotoxicity in Escherichia coli, which attenuated 2B protein expression. The release of virions from cells infected with FMDV was inhibited by amantadine, a viroporin inhibitor. The 2B protein monomers interacted with each other to form both intracellular and extracellular oligomers. The Ca(2+) concentration in the cells increased, and the integrity of the cytoplasmic membrane was disrupted in cells that expressed the 2B protein. Moreover, the 2B protein induced intense autophagy in host cells. All of the results of this study demonstrate that the FMDV 2B protein has properties that are also found in other viroporins and may be involved in the infection mechanism of FMDV.",2015 May 6,"['Ao, Da', 'Guo, Hui-Chen', 'Sun, Shi-Qi', 'Sun, De-Hui', 'Fung, To Sing', 'Wei, Yan-Quan', 'Han, Shi-Chong', 'Yao, Xue-Ping', 'Cao, Sui-Zhong', 'Liu, Ding Xiang', 'Liu, Xiang-Tao']",PLoS One,,,True
d4718ccc1c08a82371c1d7525aae8cc567ff2424,PMC,Chinese Social Media Reaction to Information about 42 Notifiable Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0126092,PMC4422708,25946020,CC BY,This study aimed to identify what information triggered social media users’ responses regarding infectious diseases. Chinese microblogs in 2012 regarding 42 infectious diseases were obtained through a keyword search in the Weiboscope database. Qualitative content analysis was performed for the posts pertinent to each keyword of the day of the year with the highest daily count. Similar posts were grouped and coded. We identified five categories of information that increased microblog traffic pertaining to infectious diseases: news of an outbreak or a case; health education / information; alternative health information / Traditional Chinese Medicine; commercial advertisement / entertainment; and social issues. News unrelated to the specified infectious diseases also led to elevated microblog traffic. Our study showcases the diverse contexts from which increased social media traffic occur. Our results will facilitate better health communication as causes underlying increased social media traffic are revealed.,2015 May 6,"['Fung, Isaac Chun-Hai', 'Hao, Yi', 'Cai, Jingxian', 'Ying, Yuchen', 'Schaible, Braydon James', 'Yu, Cynthia Mengxi', 'Tse, Zion Tsz Ho', 'Fu, King-Wa']",PLoS One,,,True
f7d4270a51caf2ea8758476bad0e0537f2d47075,PMC,Chinese Social Media Reaction to Information about 42 Notifiable Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0126092,PMC4422708,25946020,CC BY,This study aimed to identify what information triggered social media users’ responses regarding infectious diseases. Chinese microblogs in 2012 regarding 42 infectious diseases were obtained through a keyword search in the Weiboscope database. Qualitative content analysis was performed for the posts pertinent to each keyword of the day of the year with the highest daily count. Similar posts were grouped and coded. We identified five categories of information that increased microblog traffic pertaining to infectious diseases: news of an outbreak or a case; health education / information; alternative health information / Traditional Chinese Medicine; commercial advertisement / entertainment; and social issues. News unrelated to the specified infectious diseases also led to elevated microblog traffic. Our study showcases the diverse contexts from which increased social media traffic occur. Our results will facilitate better health communication as causes underlying increased social media traffic are revealed.,2015 May 6,"['Fung, Isaac Chun-Hai', 'Hao, Yi', 'Cai, Jingxian', 'Ying, Yuchen', 'Schaible, Braydon James', 'Yu, Cynthia Mengxi', 'Tse, Zion Tsz Ho', 'Fu, King-Wa']",PLoS One,,,True
471d79fab1a95464be76c77dce4a2e263ca8b443,PMC,Evaluation of a Phylogenetic Marker Based on Genomic Segment B of Infectious Bursal Disease Virus: Facilitating a Feasible Incorporation of this Segment to the Molecular Epidemiology Studies for this Viral Agent,http://dx.doi.org/10.1371/journal.pone.0125853,PMC4422720,25946336,CC BY,"BACKGROUND: Infectious bursal disease (IBD) is a highly contagious and acute viral disease, which has caused high mortality rates in birds and considerable economic losses in different parts of the world for more than two decades and it still represents a considerable threat to poultry. The current study was designed to rigorously measure the reliability of a phylogenetic marker included into segment B. This marker can facilitate molecular epidemiology studies, incorporating this segment of the viral genome, to better explain the links between emergence, spreading and maintenance of the very virulent IBD virus (vvIBDV) strains worldwide. METHODOLOGY/PRINCIPAL FINDINGS: Sequences of the segment B gene from IBDV strains isolated from diverse geographic locations were obtained from the GenBank Database; Cuban sequences were obtained in the current work. A phylogenetic marker named B-marker was assessed by different phylogenetic principles such as saturation of substitution, phylogenetic noise and high consistency. This last parameter is based on the ability of B-marker to reconstruct the same topology as the complete segment B of the viral genome. From the results obtained from B-marker, demographic history for both main lineages of IBDV regarding segment B was performed by Bayesian skyline plot analysis. Phylogenetic analysis for both segments of IBDV genome was also performed, revealing the presence of a natural reassortant strain with segment A from vvIBDV strains and segment B from non-vvIBDV strains within Cuban IBDV population. CONCLUSIONS/SIGNIFICANCE: This study contributes to a better understanding of the emergence of vvIBDV strains, describing molecular epidemiology of IBDV using the state-of-the-art methodology concerning phylogenetic reconstruction. This study also revealed the presence of a novel natural reassorted strain as possible manifest of change in the genetic structure and stability of the vvIBDV strains. Therefore, it highlights the need to obtain information about both genome segments of IBDV for molecular epidemiology studies.",2015 May 6,"['Alfonso-Morales, Abdulahi', 'Rios, Liliam', 'Martínez-Pérez, Orlando', 'Dolz, Roser', 'Valle, Rosa', 'Perera, Carmen L.', 'Bertran, Kateri', 'Frías, Maria T.', 'Ganges, Llilianne', 'Díaz de Arce, Heidy', 'Majó, Natàlia', 'Núñez, José I.', 'Pérez, Lester J.']",PLoS One,,,True
78a0953f03d4dd00f2b4234e3768d95a700202dc,PMC,Mixed Viral Infections Circulating in Hospitalized Patients with Respiratory Tract Infections in Kuwait,http://dx.doi.org/10.1155/2015/714062,PMC4423027,25983755,CC BY,"The aim of this study was to determine the frequency of viral mixed detection in hospitalized patients with respiratory tract infections and to evaluate the correlation between viral mixed detection and clinical severity. Hospitalized patients with respiratory tract infections (RTI) were investigated for 15 respiratory viruses by using sensitive molecular techniques. In total, 850 hospitalized patients aged between 3 days and 80 years were screened from September 2010 to April 2014. Among the 351 (47.8%) patients diagnosed with viral infections, viral mixed detection was identified in 49 patients (14%), with human rhinovirus (HRV) being the most common virus associated with viral mixed detection (7.1%), followed by adenovirus (AdV) (4%) and human coronavirus-OC43 (HCoV-OC43) (3.7%). The highest combination of viral mixed detection was identified with HRV and AdV (2%), followed by HRV and HCoV-OC43 (1.4%). Pneumonia and bronchiolitis were the most frequent reason for hospitalization with viral mixed detection (9.1%). There were statistical significance differences between mixed and single detection in patients diagnosed with bronchiolitis (P = 0.002) and pneumonia (P = 0.019). Our findings might indicate a significant association between respiratory virus mixed detection and the possibility of developing more severe LRTI such as bronchiolitis and pneumonia when compared with single detection.",2015 Apr 23,"['Essa, Sahar', 'Owayed, Abdullah', 'Altawalah, Haya', 'Khadadah, Mousa', 'Behbehani, Nasser', 'Al-Nakib, Widad']",Adv Virol,,,True
1b02698e082376846f59c99c449161a7a7eb737f,PMC,Drak2 Does Not Regulate TGF-β Signaling in T Cells,http://dx.doi.org/10.1371/journal.pone.0123650,PMC4423867,25951457,CC BY,"Drak2 is a serine/threonine kinase expressed highest in T cells and B cells. Drak2(-/-) mice are resistant to autoimmunity in mouse models of type 1 diabetes and multiple sclerosis. Resistance to these diseases occurs, in part, because Drak2 is required for the survival of autoreactive T cells that induce disease. However, the molecular mechanisms by which Drak2 affects T cell survival and autoimmunity are not known. A recent report demonstrated that Drak2 negatively regulated transforming growth factor-β (TGF-β) signaling in tumor cell lines. Thus, increased TGF-β signaling in the absence of Drak2 may contribute to the resistance to autoimmunity in Drak2(-/-) mice. Therefore, we examined if Drak2 functioned as a negative regulator of TGF-β signaling in T cells, and whether the enhanced susceptibility to death of Drak2(-/-) T cells was due to augmented TGF-β signaling. Using several in vitro assays to test TGF-β signaling and T cell function, we found that activation of Smad2 and Smad3, which are downstream of the TGF-β receptor, was similar between wildtype and Drak2(-/-) T cells. Furthermore, TGF-β-mediated effects on naïve T cell proliferation, activated CD8(+) T cell survival, and regulatory T cell induction was similar between wildtype and Drak2(-/-) T cells. Finally, the increased susceptibility to death in the absence of Drak2 was not due to enhanced TGF-β signaling. Together, these data suggest that Drak2 does not function as a negative regulator of TGF-β signaling in primary T cells stimulated in vitro. It is important to investigate and discern potential molecular mechanisms by which Drak2 functions in order to better understand the etiology of autoimmune diseases, as well as to validate the use of Drak2 as a target for therapeutic treatment of these diseases.",2015 May 7,"['Harris, Tarsha L.', 'McGargill, Maureen A.']",PLoS One,,,True
78c1291690eec42eb88c56d3c1e878b43409a928,PMC,Full-Genome Sequence of Pantropic Canine Coronavirus,http://dx.doi.org/10.1128/genomeA.00401-15,PMC4424302,25953186,CC BY,"Pantropic canine coronavirus (CCoV) was first detected in young dogs in Italy in 2005, but the complete genome sequence of this virus had not yet been determined. Here, we report the full-length genome sequence of the prototype strain CB/05, which showed that this virus is genetically similar to CCoV-IIa viruses.",2015 May 7,"['Decaro, Nicola', 'Mari, Viviana', 'Dowgier, Giulia', 'Elia, Gabriella', 'Lanave, Gianvito', 'Colaianni, Maria Loredana', 'Buonavoglia, Canio']",Genome Announc,,,True
7bab005205a7ee772e476d7dbcf5eee3aed12826,PMC,"Deletion of Fibrinogen-like Protein 2 (FGL-2), a Novel CD4(+) CD25(+) Treg Effector Molecule, Leads to Improved Control of Echinococcus multilocularis Infection in Mice",http://dx.doi.org/10.1371/journal.pntd.0003755,PMC4425495,25955764,CC BY,"BACKGROUND: The growth potential of the tumor-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly linked to the nature/function of the periparasitic host immune-mediated processes. We previously showed that Fibrinogen-like-protein 2 (FGL2), a novel CD4(+)CD25(+) Treg effector molecule, was over-expressed in the liver of mice experimentally infected with E. multilocularis. However, little is known about its contribution to the control of this chronic helminth infection. METHODS/FINDINGS: Key parameters for infection outcome in E. multilocularis-infected fgl2(-/-) (AE-fgl2(-/-)) and wild type (AE-WT) mice at 1 and 4 month(s) post-infection were (i) parasite load (i. e. wet weight of parasitic metacestode tissue), and (ii) parasite cell proliferation as assessed by determining E. multilocularis 14-3-3 gene expression levels. Serum FGL2 levels were measured by ELISA. Spleen cells cultured with ConA for 48h or with E. multilocularis Vesicle Fluid (VF) for 96h were analyzed ex-vivo and in-vitro. In addition, spleen cells from non-infected WT mice were cultured with rFGL2/anti-FGL2 or rIL-17A/anti-IL-17A for further functional studies. For Treg-immune-suppression-assays, purified CD4(+)CD25(+) Treg suspensions were incubated with CD4(+) effector T cells in the presence of ConA and irradiated spleen cells as APCs. Flow cytometry and qRT-PCR were used to assess Treg, Th17-, Th1-, Th2-type immune responses and maturation of dendritic cells. We showed that AE-fgl2(-/-) mice exhibited (as compared to AE-WT-animals) (a) a significantly lower parasite load with reduced proliferation activity, (b) an increased T cell proliferative response to ConA, (c) reduced Treg numbers and function, and (d) a persistent capacity of Th1 polarization and DC maturation. CONCLUSIONS: FGL2 appears as one of the key players in immune regulatory processes favoring metacestode survival by promoting Treg cell activity and IL-17A production that contributes to FGL2-regulation. Prospectively, targeting FGL2 could be an option to develop an immunotherapy against AE and other chronic parasitic diseases.",2015 May 8,"['Wang, Junhua', 'Vuitton, Dominique A.', 'Müller, Norbert', 'Hemphill, Andrew', 'Spiliotis, Markus', 'Blagosklonov, Oleg', 'Grandgirard, Denis', 'Leib, Stephen L.', 'Shalev, Itay', 'Levy, Gary', 'Lu, Xiaomei', 'Lin, Renyong', 'Wen, Hao', 'Gottstein, Bruno']",PLoS Negl Trop Dis,,,True
166142fd39f6000cf789299a7df7fedc36b300cb,PMC,Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.1004897,PMC4425567,25954804,CC BY,"In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.",2015 May 8,"['Cocita, Clément', 'Guiton, Rachel', 'Bessou, Gilles', 'Chasson, Lionel', 'Boyron, Marilyn', 'Crozat, Karine', 'Dalod, Marc']",PLoS Pathog,,,True
9ce43d96d671f1951120336aa5c311cb01c38933,PMC,Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.1004897,PMC4425567,25954804,CC BY,"In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.",2015 May 8,"['Cocita, Clément', 'Guiton, Rachel', 'Bessou, Gilles', 'Chasson, Lionel', 'Boyron, Marilyn', 'Crozat, Karine', 'Dalod, Marc']",PLoS Pathog,,,False
9ba0bcbbdf07e2bc0f584257747428a133ce438e,PMC,Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.1004897,PMC4425567,25954804,CC BY,"In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.",2015 May 8,"['Cocita, Clément', 'Guiton, Rachel', 'Bessou, Gilles', 'Chasson, Lionel', 'Boyron, Marilyn', 'Crozat, Karine', 'Dalod, Marc']",PLoS Pathog,,,False
9a2c679df3c8fb1c009087327396cb1aae759b42,PMC,Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.1004897,PMC4425567,25954804,CC BY,"In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.",2015 May 8,"['Cocita, Clément', 'Guiton, Rachel', 'Bessou, Gilles', 'Chasson, Lionel', 'Boyron, Marilyn', 'Crozat, Karine', 'Dalod, Marc']",PLoS Pathog,,,False
e15919b98993f3fd0f89d3976f4f9b3b64ad0dd5,PMC,Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.1004897,PMC4425567,25954804,CC BY,"In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.",2015 May 8,"['Cocita, Clément', 'Guiton, Rachel', 'Bessou, Gilles', 'Chasson, Lionel', 'Boyron, Marilyn', 'Crozat, Karine', 'Dalod, Marc']",PLoS Pathog,,,False
9275dfe56ef509a8204170bcade177f8a9668c44,PMC,Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.1004897,PMC4425567,25954804,CC BY,"In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.",2015 May 8,"['Cocita, Clément', 'Guiton, Rachel', 'Bessou, Gilles', 'Chasson, Lionel', 'Boyron, Marilyn', 'Crozat, Karine', 'Dalod, Marc']",PLoS Pathog,,,False
9921a4035d6dac1772ff49f43fd360286278fd28,PMC,Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus,http://dx.doi.org/10.1371/journal.ppat.1004897,PMC4425567,25954804,CC BY,"In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.",2015 May 8,"['Cocita, Clément', 'Guiton, Rachel', 'Bessou, Gilles', 'Chasson, Lionel', 'Boyron, Marilyn', 'Crozat, Karine', 'Dalod, Marc']",PLoS Pathog,,,False
99667e42abcab43a18c22be949ee54fb1822f34e,PMC,Critical care capacity in Canada: results of a national cross-sectional study,http://dx.doi.org/10.1186/s13054-015-0852-6,PMC4426537,25888116,CC BY,"INTRODUCTION: Intensive Care Units (ICUs) provide life-supporting treatment; however, resources are limited, so demand may exceed supply in the event of pandemics, environmental disasters, or in the context of an aging population. We hypothesized that comprehensive national data on ICU resources would permit a better understanding of regional differences in system capacity. METHODS: After the 2009–2010 Influenza A (H1N1) pandemic, the Canadian Critical Care Trials Group surveyed all acute care hospitals in Canada to assess ICU capacity. Using a structured survey tool administered to physicians, respiratory therapists and nurses, we determined the number of ICU beds, ventilators, and the ability to provide specialized support for respiratory failure. RESULTS: We identified 286 hospitals with 3170 ICU beds and 4982 mechanical ventilators for critically ill patients. Twenty-two hospitals had an ICU that routinely cared for children; 15 had dedicated pediatric ICUs. Per 100,000 population, there was substantial variability in provincial capacity, with a mean of 0.9 hospitals with ICUs (provincial range 0.4-2.8), 10 ICU beds capable of providing mechanical ventilation (provincial range 6–19), and 15 invasive mechanical ventilators (provincial range 10–24). There was only moderate correlation between ventilation capacity and population size (coefficient of determination (R(2)) = 0.771). CONCLUSION: ICU resources vary widely across Canadian provinces, and during times of increased demand, may result in geographic differences in the ability to care for critically ill patients. These results highlight the need to evolve inter-jurisdictional resource sharing during periods of substantial increase in demand, and provide background data for the development of appropriate critical care capacity benchmarks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0852-6) contains supplementary material, which is available to authorized users.",2015 Apr 1,"['Fowler, Robert A', 'Abdelmalik, Philip', 'Wood, Gordon', 'Foster, Denise', 'Gibney, Noel', 'Bandrauk, Natalie', 'Turgeon, Alexis F', 'Lamontagne, François', 'Kumar, Anand', 'Zarychanski, Ryan', 'Green, Rob', 'Bagshaw, Sean M', 'Stelfox, Henry T', 'Foster, Ryan', 'Dodek, Peter', 'Shaw, Susan', 'Granton, John', 'Lawless, Bernard', 'Hill, Andrea', 'Rose, Louise', 'Adhikari, Neill K', 'Scales, Damon C', 'Cook, Deborah J', 'Marshall, John C', 'Martin, Claudio', 'Jouvet, Philippe', None]",Crit Care,,,True
0f8ef4ce069bd394d71e350e4c214d8b2e425a84,PMC,Critical care capacity in Canada: results of a national cross-sectional study,http://dx.doi.org/10.1186/s13054-015-0852-6,PMC4426537,25888116,CC BY,"INTRODUCTION: Intensive Care Units (ICUs) provide life-supporting treatment; however, resources are limited, so demand may exceed supply in the event of pandemics, environmental disasters, or in the context of an aging population. We hypothesized that comprehensive national data on ICU resources would permit a better understanding of regional differences in system capacity. METHODS: After the 2009–2010 Influenza A (H1N1) pandemic, the Canadian Critical Care Trials Group surveyed all acute care hospitals in Canada to assess ICU capacity. Using a structured survey tool administered to physicians, respiratory therapists and nurses, we determined the number of ICU beds, ventilators, and the ability to provide specialized support for respiratory failure. RESULTS: We identified 286 hospitals with 3170 ICU beds and 4982 mechanical ventilators for critically ill patients. Twenty-two hospitals had an ICU that routinely cared for children; 15 had dedicated pediatric ICUs. Per 100,000 population, there was substantial variability in provincial capacity, with a mean of 0.9 hospitals with ICUs (provincial range 0.4-2.8), 10 ICU beds capable of providing mechanical ventilation (provincial range 6–19), and 15 invasive mechanical ventilators (provincial range 10–24). There was only moderate correlation between ventilation capacity and population size (coefficient of determination (R(2)) = 0.771). CONCLUSION: ICU resources vary widely across Canadian provinces, and during times of increased demand, may result in geographic differences in the ability to care for critically ill patients. These results highlight the need to evolve inter-jurisdictional resource sharing during periods of substantial increase in demand, and provide background data for the development of appropriate critical care capacity benchmarks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0852-6) contains supplementary material, which is available to authorized users.",2015 Apr 1,"['Fowler, Robert A', 'Abdelmalik, Philip', 'Wood, Gordon', 'Foster, Denise', 'Gibney, Noel', 'Bandrauk, Natalie', 'Turgeon, Alexis F', 'Lamontagne, François', 'Kumar, Anand', 'Zarychanski, Ryan', 'Green, Rob', 'Bagshaw, Sean M', 'Stelfox, Henry T', 'Foster, Ryan', 'Dodek, Peter', 'Shaw, Susan', 'Granton, John', 'Lawless, Bernard', 'Hill, Andrea', 'Rose, Louise', 'Adhikari, Neill K', 'Scales, Damon C', 'Cook, Deborah J', 'Marshall, John C', 'Martin, Claudio', 'Jouvet, Philippe', None]",Crit Care,,,True
489581af56b842073e88412d6d28cf89c2e08d0e,PMC,"Avoidable errors in the modelling of outbreaks of emerging pathogens, with special reference to Ebola",http://dx.doi.org/10.1098/rspb.2015.0347,PMC4426634,25833863,CC BY,"As an emergent infectious disease outbreak unfolds, public health response is reliant on information on key epidemiological quantities, such as transmission potential and serial interval. Increasingly, transmission models fit to incidence data are used to estimate these parameters and guide policy. Some widely used modelling practices lead to potentially large errors in parameter estimates and, consequently, errors in model-based forecasts. Even more worryingly, in such situations, confidence in parameter estimates and forecasts can itself be far overestimated, leading to the potential for large errors that mask their own presence. Fortunately, straightforward and computationally inexpensive alternatives exist that avoid these problems. Here, we first use a simulation study to demonstrate potential pitfalls of the standard practice of fitting deterministic models to cumulative incidence data. Next, we demonstrate an alternative based on stochastic models fit to raw data from an early phase of 2014 West Africa Ebola virus disease outbreak. We show not only that bias is thereby reduced, but that uncertainty in estimates and forecasts is better quantified and that, critically, lack of model fit is more readily diagnosed. We conclude with a short list of principles to guide the modelling response to future infectious disease outbreaks.",2015 May 7,"['King, Aaron A.', 'Domenech de Cellès, Matthieu', 'Magpantay, Felicia M. G.', 'Rohani, Pejman']",Proc Biol Sci,,,True
15a1cb9e790f884e0513e9f0112a909e95a96c67,PMC,"Avoidable errors in the modelling of outbreaks of emerging pathogens, with special reference to Ebola",http://dx.doi.org/10.1098/rspb.2015.0347,PMC4426634,25833863,CC BY,"As an emergent infectious disease outbreak unfolds, public health response is reliant on information on key epidemiological quantities, such as transmission potential and serial interval. Increasingly, transmission models fit to incidence data are used to estimate these parameters and guide policy. Some widely used modelling practices lead to potentially large errors in parameter estimates and, consequently, errors in model-based forecasts. Even more worryingly, in such situations, confidence in parameter estimates and forecasts can itself be far overestimated, leading to the potential for large errors that mask their own presence. Fortunately, straightforward and computationally inexpensive alternatives exist that avoid these problems. Here, we first use a simulation study to demonstrate potential pitfalls of the standard practice of fitting deterministic models to cumulative incidence data. Next, we demonstrate an alternative based on stochastic models fit to raw data from an early phase of 2014 West Africa Ebola virus disease outbreak. We show not only that bias is thereby reduced, but that uncertainty in estimates and forecasts is better quantified and that, critically, lack of model fit is more readily diagnosed. We conclude with a short list of principles to guide the modelling response to future infectious disease outbreaks.",2015 May 7,"['King, Aaron A.', 'Domenech de Cellès, Matthieu', 'Magpantay, Felicia M. G.', 'Rohani, Pejman']",Proc Biol Sci,,,True
fe9776ca32f2901c58c1df81f6d9767803909869,PMC,"West Nile Virus Positive Blood Donation and Subsequent Entomological Investigation, Austria, 2014",http://dx.doi.org/10.1371/journal.pone.0126381,PMC4427133,25961567,CC BY,"The detection of West Nile virus (WNV) nucleic acid in a blood donation from Vienna, Austria, as well as in Culex pipiens pupae and egg rafts, sampled close to the donor’s residence, is reported. Complete genomic sequences of the human- and mosquito-derived viruses were established, genetically compared and phylogenetically analyzed. The viruses were not identical, but closely related to each other and to recent Czech and Italian isolates, indicating co-circulation of related WNV strains within a confined geographic area. The detection of WNV in a blood donation originating from an area with low WNV prevalence in humans (only three serologically diagnosed cases between 2008 and 2014) is surprising and emphasizes the importance of WNV nucleic acid testing of blood donations even in such areas, along with active mosquito surveillance programs.",2015 May 11,"['Kolodziejek, Jolanta', 'Seidel, Bernhard', 'Jungbauer, Christof', 'Dimmel, Katharina', 'Kolodziejek, Michael', 'Rudolf, Ivo', 'Hubálek, Zdenek', 'Allerberger, Franz', 'Nowotny, Norbert']",PLoS One,,,True
07420d39191900a262a4c5afff61e0ef80eac575,PMC,Regulatory Role of Small Nucleolar RNAs in Human Diseases,http://dx.doi.org/10.1155/2015/206849,PMC4427830,26060813,CC BY,"Small nucleolar RNAs (snoRNAs) are appreciable players in gene expression regulation in human cells. The canonical function of box C/D and box H/ACA snoRNAs is posttranscriptional modification of ribosomal RNAs (rRNAs), namely, 2′-O-methylation and pseudouridylation, respectively. A series of independent studies demonstrated that snoRNAs, as well as other noncoding RNAs, serve as the source of various short regulatory RNAs. Some snoRNAs and their fragments can also participate in the regulation of alternative splicing and posttranscriptional modification of mRNA. Alterations in snoRNA expression in human cells can affect numerous vital cellular processes. SnoRNA level in human cells, blood serum, and plasma presents a promising target for diagnostics and treatment of human pathologies. Here we discuss the relation between snoRNAs and oncological, neurodegenerative, and viral diseases and also describe changes in snoRNA level in response to artificial stress and some drugs.",2015 Apr 28,"['Stepanov, Grigory A.', 'Filippova, Julia A.', 'Komissarov, Andrey B.', 'Kuligina, Elena V.', 'Richter, Vladimir A.', 'Semenov, Dmitry V.']",Biomed Res Int,,,True
d4225ab29dd0f4b357b4667e22037e78b8d95391,PMC,Household practices related to disease transmission between animals and humans in rural Cambodia,http://dx.doi.org/10.1186/s12889-015-1811-5,PMC4427931,25952633,CC BY,"BACKGROUND: Zoonotic diseases are disproportionately affecting poor societies in low-income countries and pose a growing threat to public health and global food security. Rural Cambodian households may face an increased likelihood of exposure to zoonotic diseases as people there live in close association with livestock. The objectives of the study was to identify practices known to influence zoonosis transmission in rural Cambodian households and relate the practices to agro-ecological region, socio-economic position, demographics, livestock management and zoonosis awareness. METHODS: The study was conducted in three different agro-ecological regions of Cambodia; 10 villages each in the central lowlands, north-west wetlands and on the south coast, where information was obtained in questionnaires administered to 300 households, and 30 village heads and animal health workers. RESULTS: Descriptive analysis revealed a gender difference in responsibility for livestock and that the main purpose of raising livestock was for sale. Few respondents (6%) perceived a likelihood of disease transmission in their village between livestock, humans and wildlife, despite household practices related to zoonosis transmission being common. More than one-forth of households practised behaviours such as culling sick animals for consumption, eating animals found dead and allowing animals to enter sleeping and food preparation areas. Associations between household practices and possible explanatory factors were analysed with multivariable models using generalised estimation equations to account for clustering of practices within villages. Factors found to influence household practices were agro-ecological region, socio-economic position, number of people in the household, livestock species reared and awareness of zoonoses. CONCLUSIONS: Cambodia has experienced numerous fatal human cases of zoonotic influenza and extensive influenza information campaigns have been run, yet only a few of the households surveyed here reported the threat of zoonosis to be a concern in their village. Zoonosis awareness was positively related to hand washing behaviour, but other practices associated with an increased or decreased likelihood of exposure to zoonotic pathogens were unaffected by awareness. The findings indicate a knowledge-to-action gap among rural farmers and highlight the necessity for reconstructed interventions in zoonotic disease control. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1811-5) contains supplementary material, which is available to authorized users.",2015 May 9,"['Osbjer, Kristina', 'Boqvist, Sofia', 'Sokerya, Seng', 'Kannarath, Chheng', 'San, Sorn', 'Davun, Holl', 'Magnusson, Ulf']",BMC Public Health,,,False
76813504d1a92988df75461d6994e860c5cb9ba1,PMC,Household practices related to disease transmission between animals and humans in rural Cambodia,http://dx.doi.org/10.1186/s12889-015-1811-5,PMC4427931,25952633,CC BY,"BACKGROUND: Zoonotic diseases are disproportionately affecting poor societies in low-income countries and pose a growing threat to public health and global food security. Rural Cambodian households may face an increased likelihood of exposure to zoonotic diseases as people there live in close association with livestock. The objectives of the study was to identify practices known to influence zoonosis transmission in rural Cambodian households and relate the practices to agro-ecological region, socio-economic position, demographics, livestock management and zoonosis awareness. METHODS: The study was conducted in three different agro-ecological regions of Cambodia; 10 villages each in the central lowlands, north-west wetlands and on the south coast, where information was obtained in questionnaires administered to 300 households, and 30 village heads and animal health workers. RESULTS: Descriptive analysis revealed a gender difference in responsibility for livestock and that the main purpose of raising livestock was for sale. Few respondents (6%) perceived a likelihood of disease transmission in their village between livestock, humans and wildlife, despite household practices related to zoonosis transmission being common. More than one-forth of households practised behaviours such as culling sick animals for consumption, eating animals found dead and allowing animals to enter sleeping and food preparation areas. Associations between household practices and possible explanatory factors were analysed with multivariable models using generalised estimation equations to account for clustering of practices within villages. Factors found to influence household practices were agro-ecological region, socio-economic position, number of people in the household, livestock species reared and awareness of zoonoses. CONCLUSIONS: Cambodia has experienced numerous fatal human cases of zoonotic influenza and extensive influenza information campaigns have been run, yet only a few of the households surveyed here reported the threat of zoonosis to be a concern in their village. Zoonosis awareness was positively related to hand washing behaviour, but other practices associated with an increased or decreased likelihood of exposure to zoonotic pathogens were unaffected by awareness. The findings indicate a knowledge-to-action gap among rural farmers and highlight the necessity for reconstructed interventions in zoonotic disease control. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1811-5) contains supplementary material, which is available to authorized users.",2015 May 9,"['Osbjer, Kristina', 'Boqvist, Sofia', 'Sokerya, Seng', 'Kannarath, Chheng', 'San, Sorn', 'Davun, Holl', 'Magnusson, Ulf']",BMC Public Health,,,False
724974cf3a9e24f32408a976803e16254a9803c1,PMC,Household practices related to disease transmission between animals and humans in rural Cambodia,http://dx.doi.org/10.1186/s12889-015-1811-5,PMC4427931,25952633,CC BY,"BACKGROUND: Zoonotic diseases are disproportionately affecting poor societies in low-income countries and pose a growing threat to public health and global food security. Rural Cambodian households may face an increased likelihood of exposure to zoonotic diseases as people there live in close association with livestock. The objectives of the study was to identify practices known to influence zoonosis transmission in rural Cambodian households and relate the practices to agro-ecological region, socio-economic position, demographics, livestock management and zoonosis awareness. METHODS: The study was conducted in three different agro-ecological regions of Cambodia; 10 villages each in the central lowlands, north-west wetlands and on the south coast, where information was obtained in questionnaires administered to 300 households, and 30 village heads and animal health workers. RESULTS: Descriptive analysis revealed a gender difference in responsibility for livestock and that the main purpose of raising livestock was for sale. Few respondents (6%) perceived a likelihood of disease transmission in their village between livestock, humans and wildlife, despite household practices related to zoonosis transmission being common. More than one-forth of households practised behaviours such as culling sick animals for consumption, eating animals found dead and allowing animals to enter sleeping and food preparation areas. Associations between household practices and possible explanatory factors were analysed with multivariable models using generalised estimation equations to account for clustering of practices within villages. Factors found to influence household practices were agro-ecological region, socio-economic position, number of people in the household, livestock species reared and awareness of zoonoses. CONCLUSIONS: Cambodia has experienced numerous fatal human cases of zoonotic influenza and extensive influenza information campaigns have been run, yet only a few of the households surveyed here reported the threat of zoonosis to be a concern in their village. Zoonosis awareness was positively related to hand washing behaviour, but other practices associated with an increased or decreased likelihood of exposure to zoonotic pathogens were unaffected by awareness. The findings indicate a knowledge-to-action gap among rural farmers and highlight the necessity for reconstructed interventions in zoonotic disease control. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1811-5) contains supplementary material, which is available to authorized users.",2015 May 9,"['Osbjer, Kristina', 'Boqvist, Sofia', 'Sokerya, Seng', 'Kannarath, Chheng', 'San, Sorn', 'Davun, Holl', 'Magnusson, Ulf']",BMC Public Health,,,True
be86d94be6483de622f67e0c098684e4982c0441,PMC,Ethics-sensitivity of the Ghana national integrated strategic response plan for pandemic influenza,http://dx.doi.org/10.1186/s12910-015-0025-9,PMC4427965,25947354,CC BY,"BACKGROUND: Many commentators call for a more ethical approach to planning for influenza pandemics. In the developed world, some pandemic preparedness plans have already been examined from an ethical viewpoint. This paper assesses the attention given to ethics issues by the Ghana National Integrated Strategic Plan for Pandemic Influenza (NISPPI). METHODS: We critically analyzed the Ghana NISPPI’s sensitivity to ethics issues to determine how well it reflects ethical commitments and principles identified in our review of global pandemic preparedness literature, existing pandemic plans, and relevant ethics frameworks. RESULTS: This paper reveals that important ethical issues have not been addressed in the Ghana NISPPI. Several important ethical issues are unanticipated, unacknowledged, and unplanned for. These include guidelines on allocation of scarce resources, the duties of healthcare workers, ethics-sensitive operational guidelines/protocols, and compensation programs. The NISPPI also pays scant attention to use of vaccines and antivirals, border issues and cooperation with neighboring countries, justification for delineated actions, and outbreak simulations. Feedback and communication plans are nebulous, while leadership, coordination, and budgeting are quite detailed. With respect to presentation, the NISPPI’s text is organized around five thematic areas. While each area implicates ethical issues, NISPPI treatment of these areas consistently fails to address them. CONCLUSIONS: Our analysis reveals a lack of consideration of ethics by the NISPPI. We contend that, while the plan’s content and fundamental assumptions provide support for implementation of the delineated public health actions, its consideration of ethical issues is poor. Deficiencies include a failure to incorporate guidelines that ensure fair distribution of scarce resources and a lack of justification for delineated procedures. Until these deficiencies are recognized and addressed, Ghana runs the risk of rolling out unjust and ethically indefensible actions with real negative effects in the event of a pandemic. Soliciting inputs from the public and consultation with ethicists during the next revision of the NISPPI will be useful in addressing these issues.",2015 May 7,"['Laar, Amos', 'DeBruin, Debra']",BMC Med Ethics,,,True
fc89cc67ce1d4e381a17de2c92a9b882f264197d,PMC,Serological Evidence of Influenza A Viruses in Frugivorous Bats from Africa,http://dx.doi.org/10.1371/journal.pone.0127035,PMC4429104,25965069,CC BY,"Bats are likely natural hosts for a range of zoonotic viruses such as Marburg, Ebola, Rabies, as well as for various Corona- and Paramyxoviruses. In 2009/10, researchers discovered RNA of two novel influenza virus subtypes – H17N10 and H18N11 – in Central and South American fruit bats. The identification of bats as possible additional reservoir for influenza A viruses raises questions about the role of this mammalian taxon in influenza A virus ecology and possible public health relevance. As molecular testing can be limited by a short time window in which the virus is present, serological testing provides information about past infections and virus spread in populations after the virus has been cleared. This study aimed at screening available sera from 100 free-ranging, frugivorous bats (Eidolon helvum) sampled in 2009/10 in Ghana, for the presence of antibodies against the complete panel of influenza A haemagglutinin (HA) types ranging from H1 to H18 by means of a protein microarray platform. This technique enables simultaneous serological testing against multiple recombinant HA-types in 5μl of serum. Preliminary results indicate serological evidence against avian influenza subtype H9 in about 30% of the animals screened, with low-level cross-reactivity to phylogenetically closely related subtypes H8 and H12. To our knowledge, this is the first report of serological evidence of influenza A viruses other than H17 and H18 in bats. As avian influenza subtype H9 is associated with human infections, the implications of our findings from a public health context remain to be investigated.",2015 May 12,"['Freidl, Gudrun Stephanie', 'Binger, Tabea', 'Müller, Marcel Alexander', 'de Bruin, Erwin', 'van Beek, Janko', 'Corman, Victor Max', 'Rasche, Andrea', 'Drexler, Jan Felix', 'Sylverken, Augustina', 'Oppong, Samuel K.', 'Adu-Sarkodie, Yaw', 'Tschapka, Marco', 'Cottontail, Veronika M.', 'Drosten, Christian', 'Koopmans, Marion']",PLoS One,,,True
c9c9e146899b877f56ceb3a671fa104787bdf736,PMC,"Ecohealth research in Southeast Asia: past, present and the way forward",http://dx.doi.org/10.1186/2049-9957-4-5,PMC4429815,25973200,CC BY,"Ecohealth is a comprehensive approach to understanding health at its human, animal and environmental interface in a socio-ecological systems context. This approach was introduced widely in Southeast Asia (SEA) by the Canadian International Development Research Centre (IDRC) in the late 2000s. Aimed at addressing the problem of emerging infectious diseases (EIDs), numerous such projects and activities have been generated throughout the region. Ecohealth is increasingly converging with the One Health approach, as both movements emphasise a holistic understanding to health. We conducted a scoping review by considering all of the Ecohealth programmes, initiatives and projects that have been implemented in SEA since the introduction of the approach, and also gathered information from peer-reviewed literature. The objective of this paper is to review Ecohealth activities within SEA over the last 10 years to address the lessons learned, challenges faced and the way forward for Ecohealth in the region. Activities range from those focusing purely on capacity, projects focusing on research and projects covering both. Achievements to date include, for example, research contributing to the field of infectious diseases in relation to social ecological factors and associated urbanisation and agricultural intensification. Challenges remain at the project design and implementation level, in the available capacity and coordination to develop Ecohealth research teams in the countries, gauging teams’ assimilation of Ecohealth’s underlying tenets and their translation into sustainable disease prevention and control, as well as in the ability to scale up Ecohealth projects. We suggest that the way forward for Ecohealth should be from a regional perspective in terms of research, training and policy translation using Ecohealth in combination with the One Health approach. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-4-5) contains supplementary material, which is available to authorized users.",2015 Jan 29,"['Nguyen-Viet, Hung', 'Doria, Siobhan', 'Tung, Dinh Xuan', 'Mallee, Hein', 'Wilcox, Bruce A', 'Grace, Delia']",Infect Dis Poverty,,,False
1495c1fa93db3b9a5d12b5ae15ff0c8639b83452,PMC,"Ecohealth research in Southeast Asia: past, present and the way forward",http://dx.doi.org/10.1186/2049-9957-4-5,PMC4429815,25973200,CC BY,"Ecohealth is a comprehensive approach to understanding health at its human, animal and environmental interface in a socio-ecological systems context. This approach was introduced widely in Southeast Asia (SEA) by the Canadian International Development Research Centre (IDRC) in the late 2000s. Aimed at addressing the problem of emerging infectious diseases (EIDs), numerous such projects and activities have been generated throughout the region. Ecohealth is increasingly converging with the One Health approach, as both movements emphasise a holistic understanding to health. We conducted a scoping review by considering all of the Ecohealth programmes, initiatives and projects that have been implemented in SEA since the introduction of the approach, and also gathered information from peer-reviewed literature. The objective of this paper is to review Ecohealth activities within SEA over the last 10 years to address the lessons learned, challenges faced and the way forward for Ecohealth in the region. Activities range from those focusing purely on capacity, projects focusing on research and projects covering both. Achievements to date include, for example, research contributing to the field of infectious diseases in relation to social ecological factors and associated urbanisation and agricultural intensification. Challenges remain at the project design and implementation level, in the available capacity and coordination to develop Ecohealth research teams in the countries, gauging teams’ assimilation of Ecohealth’s underlying tenets and their translation into sustainable disease prevention and control, as well as in the ability to scale up Ecohealth projects. We suggest that the way forward for Ecohealth should be from a regional perspective in terms of research, training and policy translation using Ecohealth in combination with the One Health approach. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-4-5) contains supplementary material, which is available to authorized users.",2015 Jan 29,"['Nguyen-Viet, Hung', 'Doria, Siobhan', 'Tung, Dinh Xuan', 'Mallee, Hein', 'Wilcox, Bruce A', 'Grace, Delia']",Infect Dis Poverty,,,True
60f1a9fff7e34e6a528a2a06dedb23700c87e114,PMC,Environmental Conditions Affect Exhalation of H3N2 Seasonal and Variant Influenza Viruses and Respiratory Droplet Transmission in Ferrets,http://dx.doi.org/10.1371/journal.pone.0125874,PMC4430532,25969995,CC0,"The seasonality of influenza virus infections in temperate climates and the role of environmental conditions like temperature and humidity in the transmission of influenza virus through the air are not well understood. Using ferrets housed at four different environmental conditions, we evaluated the respiratory droplet transmission of two influenza viruses (a seasonal H3N2 virus and an H3N2 variant virus, the etiologic virus of a swine to human summertime infection) and concurrently characterized the aerosol shedding profiles of infected animals. Comparisons were made among the different temperature and humidity conditions and between the two viruses to determine if the H3N2 variant virus exhibited enhanced capabilities that may have contributed to the infections occurring in the summer. We report here that although increased levels of H3N2 variant virus were found in ferret nasal wash and exhaled aerosol samples compared to the seasonal H3N2 virus, enhanced respiratory droplet transmission was not observed under any of the environmental settings. However, overall environmental conditions were shown to modulate the frequency of influenza virus transmission through the air. Transmission occurred most frequently at 23°C/30%RH, while the levels of infectious virus in aerosols exhaled by infected ferrets agree with these results. Improving our understanding of how environmental conditions affect influenza virus infectivity and transmission may reveal ways to better protect the public against influenza virus infections.",2015 May 13,"['Gustin, Kortney M.', 'Belser, Jessica A.', 'Veguilla, Vic', 'Zeng, Hui', 'Katz, Jacqueline M.', 'Tumpey, Terrence M.', 'Maines, Taronna R.']",PLoS One,,,True
10093bdac52a5e404369bff30a4d38b2bde54276,PMC,Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry,http://dx.doi.org/10.12688/f1000research.6085.2,PMC4431382,26069727,CC BY,"Emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. The former was the only available intervention when the current unprecedented Ebolavirus (EBOV) outbreak in West Africa began. Prior to this, the development of EBOV vaccines and anti-viral therapies required time and resources that were not available. Therefore, focus has turned to re-purposing of existing, licenced medicines that may limit the morbidity and mortality rates of EBOV and could be used immediately. Here we test three such medicines and measure their ability to inhibit pseudotype viruses (PVs) of two EBOV species, Marburg virus (MARV) and avian influenza H5 (FLU-H5). We confirm the ability of chloroquine (CQ) to inhibit viral entry in a pH specific manner. The commonly used proton pump inhibitors, Omeprazole and Esomeprazole were also able to inhibit entry of all PVs tested but at higher drug concentrations than may be achieved in vivo. We propose CQ as a priority candidate to consider for treatment of EBOV.",2015 Feb 10,"['Long, Jason', 'Wright, Edward', 'Molesti, Eleonora', 'Temperton, Nigel', 'Barclay, Wendy']",F1000Res,,,True
4c4f2d56d08bd5890b44418d237ee5a81afd99fa,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.15.010415,PMC4431563,,CC BY,,2015 Apr 1,,Bull World Health Organ,,,False
eabb427018b4decc5d1e04772814238be2a6d9d6,PMC,Forecasting the 2013–2014 Influenza Season Using Wikipedia,http://dx.doi.org/10.1371/journal.pcbi.1004239,PMC4431683,25974758,CC0,"Infectious diseases are one of the leading causes of morbidity and mortality around the world; thus, forecasting their impact is crucial for planning an effective response strategy. According to the Centers for Disease Control and Prevention (CDC), seasonal influenza affects 5% to 20% of the U.S. population and causes major economic impacts resulting from hospitalization and absenteeism. Understanding influenza dynamics and forecasting its impact is fundamental for developing prevention and mitigation strategies. We combine modern data assimilation methods with Wikipedia access logs and CDC influenza-like illness (ILI) reports to create a weekly forecast for seasonal influenza. The methods are applied to the 2013-2014 influenza season but are sufficiently general to forecast any disease outbreak, given incidence or case count data. We adjust the initialization and parametrization of a disease model and show that this allows us to determine systematic model bias. In addition, we provide a way to determine where the model diverges from observation and evaluate forecast accuracy. Wikipedia article access logs are shown to be highly correlated with historical ILI records and allow for accurate prediction of ILI data several weeks before it becomes available. The results show that prior to the peak of the flu season, our forecasting method produced 50% and 95% credible intervals for the 2013-2014 ILI observations that contained the actual observations for most weeks in the forecast. However, since our model does not account for re-infection or multiple strains of influenza, the tail of the epidemic is not predicted well after the peak of flu season has passed.",2015 May 14,"['Hickmann, Kyle S.', 'Fairchild, Geoffrey', 'Priedhorsky, Reid', 'Generous, Nicholas', 'Hyman, James M.', 'Deshpande, Alina', 'Del Valle, Sara Y.']",PLoS Comput Biol,,,True
0b3baf8685f86b7d620418cb17d29a60ce1d498a,PMC,Transcriptional Profiling of Host Gene Expression in Chicken Embryo Fibroblasts Infected with Reticuloendotheliosis Virus Strain HA1101,http://dx.doi.org/10.1371/journal.pone.0126992,PMC4431687,25973612,CC BY,"Reticuloendotheliosis virus (REV), a member of the Gammaretrovirus genus in the Retroviridae family, causes an immunosuppressive, oncogenic and runting-stunting syndrome in multiple avian hosts. To better understand the host interactions at the transcriptional level, microarray data analysis was performed in chicken embryo fibroblast cells at 1, 3, 5, and 7 days after infection with REV. This study identified 1,785 differentially expressed genes that were classified into several functional groups including signal transduction, immune response, biological adhesion and endocytosis. Significant differences were mainly observed in the expression of genes involved in the immune response, especially during the later post-infection time points. These results revealed that differentially expressed genes IL6, STAT1, MyD88, TLRs, NF-κB, IRF-7, and ISGs play important roles in the pathogenicity of REV infection. Our study is the first to use microarray analysis to investigate REV, and these findings provide insights into the underlying mechanisms of the host antiviral response and the molecular basis of viral pathogenesis.",2015 May 14,"['Miao, Ji', 'Bao, Yanqing', 'Ye, Jianqiang', 'Shao, Hongxia', 'Qian, Kun', 'Qin, Aijian']",PLoS One,,,True
7b430982b2fc7bb7b3e56ad2b58bb42a431985f6,PMC,Antimicrobial Air Filters Using Natural Euscaphis japonica Nanoparticles,http://dx.doi.org/10.1371/journal.pone.0126481,PMC4431859,25974109,CC BY,"Controlling bioaerosols has become more important with increasing participation in indoor activities. Treatments using natural-product nanomaterials are a promising technique because of their relatively low toxicity compared to inorganic nanomaterials such as silver nanoparticles or carbon nanotubes. In this study, antimicrobial filters were fabricated from natural Euscaphis japonica nanoparticles, which were produced by nebulizing E. japonica extract. The coated filters were assessed in terms of pressure drop, antimicrobial activity, filtration efficiency, major chemical components, and cytotoxicity. Pressure drop and antimicrobial activity increased as a function of nanoparticle deposition time (590, 855, and 1150 µg/cm2(filter) at 3-, 6-, and 9-min depositions, respectively). In filter tests, the antimicrobial efficacy was greater against Staphylococcus epidermidis than Micrococcus luteus; ~61, ~73, and ~82% of M. luteus cells were inactivated on filters that had been coated for 3, 6, and 9 min, respectively, while the corresponding values were ~78, ~88, and ~94% with S. epidermidis. Although statistically significant differences in filtration performance were not observed between samples as a function of deposition time, the average filtration efficacy was slightly higher for S. epidermidis aerosols (~97%) than for M. luteus aerosols (~95%). High-performance liquid chromatography (HPLC) and electrospray ionization-tandem mass spectrometry (ESI/MS) analyses confirmed that the major chemical compounds in the E. japonica extract were 1(ß)-O-galloyl pedunculagin, quercetin-3-O-glucuronide, and kaempferol-3-O-glucoside. In vitro cytotoxicity and disk diffusion tests showed that E. japonica nanoparticles were less toxic and exhibited stronger antimicrobial activity toward some bacterial strains than a reference soluble nickel compound, which is classified as a human carcinogen. This study provides valuable information for the development of a bioaerosol control system that is environmental friendly and suitable for use in indoor environments.",2015 May 14,"['Hwang, Gi Byoung', 'Heo, Ki Joon', 'Yun, Ji Ho', 'Lee, Jung Eun', 'Lee, Hee Ju', 'Nho, Chu Won', 'Bae, Gwi- Nam', 'Jung, Jae Hee']",PLoS One,,,True
d3507b9c61a3a5cd568e7f94bc6c99506dd9c152,PMC,Evidence for Human Norovirus Infection of Dogs in the United Kingdom,http://dx.doi.org/10.1128/JCM.02778-14,PMC4432062,25832298,CC BY,"Human noroviruses (HuNoVs) are a major cause of viral gastroenteritis, with an estimated 3 million cases per year in the United Kingdom. HuNoVs have recently been isolated from pet dogs in Europe (M. Summa, C.-H. von Bonsdorff, and L. Maunula, J Clin Virol 53:244–247, 2012, http://dx.doi.org/10.1016/j.jcv.2011.12.014), raising concerns about potential zoonotic infections. With 31% of United Kingdom households owning a dog, this could prove to be an important transmission route. To examine this risk, canine tissues were studied for their ability to bind to HuNoV in vitro. In addition, canine stool samples were analyzed for the presence of viral nucleic acid, and canine serum samples were tested for the presence of anti-HuNoV antibodies. The results showed that seven different genotypes of HuNoV virus-like particles (VLPs) can bind to canine gastrointestinal tissue, suggesting that infection is at least theoretically possible. Although HuNoV RNA was not identified in stool samples from 248 dogs, serological evidence of previous exposure to HuNoV was obtained in 43/325 canine serum samples. Remarkably, canine seroprevalence for different HuNoV genotypes mirrored the seroprevalence in the human population. Though entry and replication within cells have not been demonstrated, the canine serological data indicate that dogs produce an immune response to HuNoV, implying productive infection. In conclusion, this study reveals zoonotic implications for HuNoV, and to elucidate the significance of this finding, further epidemiological and molecular investigations will be essential.",2015 Jun 14,"['Caddy, Sarah L.', 'de Rougemont, Alexis', 'Emmott, Edward', 'El-Attar, Laila', 'Mitchell, Judy A.', 'Hollinshead, Michael', 'Belliot, Gael', 'Brownlie, Joe', 'Le Pendu, Jacques', 'Goodfellow, Ian']",J Clin Microbiol,,,False
bb76fcd0194eeda7dc70702dacad97492a497bea,PMC,Evidence for Human Norovirus Infection of Dogs in the United Kingdom,http://dx.doi.org/10.1128/JCM.02778-14,PMC4432062,25832298,CC BY,"Human noroviruses (HuNoVs) are a major cause of viral gastroenteritis, with an estimated 3 million cases per year in the United Kingdom. HuNoVs have recently been isolated from pet dogs in Europe (M. Summa, C.-H. von Bonsdorff, and L. Maunula, J Clin Virol 53:244–247, 2012, http://dx.doi.org/10.1016/j.jcv.2011.12.014), raising concerns about potential zoonotic infections. With 31% of United Kingdom households owning a dog, this could prove to be an important transmission route. To examine this risk, canine tissues were studied for their ability to bind to HuNoV in vitro. In addition, canine stool samples were analyzed for the presence of viral nucleic acid, and canine serum samples were tested for the presence of anti-HuNoV antibodies. The results showed that seven different genotypes of HuNoV virus-like particles (VLPs) can bind to canine gastrointestinal tissue, suggesting that infection is at least theoretically possible. Although HuNoV RNA was not identified in stool samples from 248 dogs, serological evidence of previous exposure to HuNoV was obtained in 43/325 canine serum samples. Remarkably, canine seroprevalence for different HuNoV genotypes mirrored the seroprevalence in the human population. Though entry and replication within cells have not been demonstrated, the canine serological data indicate that dogs produce an immune response to HuNoV, implying productive infection. In conclusion, this study reveals zoonotic implications for HuNoV, and to elucidate the significance of this finding, further epidemiological and molecular investigations will be essential.",2015 Jun 14,"['Caddy, Sarah L.', 'de Rougemont, Alexis', 'Emmott, Edward', 'El-Attar, Laila', 'Mitchell, Judy A.', 'Hollinshead, Michael', 'Belliot, Gael', 'Brownlie, Joe', 'Le Pendu, Jacques', 'Goodfellow, Ian']",J Clin Microbiol,,,True
7a7e072c8c70ce3f42148a4a4bbbc8800b2a03f2,PMC,Strand-Specific Quantitative Reverse Transcription-Polymerase Chain Reaction Assay for Measurement of Arenavirus Genomic and Antigenomic RNAs,http://dx.doi.org/10.1371/journal.pone.0120043,PMC4433285,25978311,CC BY,"Arenaviruses are bi-segmented, single-stranded RNA viruses that cause significant human disease. The manner in which they regulate the replication of their genome is not well-understood. This is partly due to the absence of a highly sensitive assay to measure individual species of arenavirus replicative RNAs. To overcome this obstacle, we designed a quantitative reverse transcription (RT)-PCR assay for selective quantitation of each of the lymphocytic choriomeningitis virus (LCMV) genomic or antigenomic RNAs. During the course of assay design, we identified a nonspecific priming phenomenon whereby, in the absence of an RT primer, cDNAs complementary to each of the LCMV replicative RNA species are generated during RT. We successfully circumvented this nonspecific priming event through the use of biotinylated primers in the RT reaction, which permitted affinity purification of primer-specific cDNAs using streptavidin-coated magnetic beads. As proof of principle, we used the assay to map the dynamics of LCMV replication at acute and persistent time points and to determine the quantities of genomic and antigenomic RNAs that are incorporated into LCMV particles. This assay can be adapted to measure total S or L segment-derived viral RNAs and therefore represents a highly sensitive diagnostic platform to screen for LCMV infection in rodent and human tissue samples and can also be used to quantify virus-cell attachment.",2015 May 15,"['Haist, Kelsey', 'Ziegler, Christopher', 'Botten, Jason']",PLoS One,,,True
42f6f50759cb4c433e8c1ff0d695bdb32ae97df9,PMC,plethy: management of whole body plethysmography data in R,http://dx.doi.org/10.1186/s12859-015-0547-7,PMC4434826,25924931,CC BY,"BACKGROUND: Characterization of respiratory phenotypes can enhance complex trait and genomic studies involving allergic/autoimmune and infectious diseases. Many aspects of respiration can be measured using devices known as plethysmographs that can measure thoracic movement. One such approach (the Buxco platform) performs unrestrained whole body plethysmography on mice which infers thoracic movements from pressure differences from the act of inhalation and exhalation. While proprietary software is available to perform basic statistical analysis as part of machine’s bundled software, it is desirable to be able to incorporate these analyses into high-throughput pipelines and integrate them with other data types, as well as leverage the wealth of analytic and visualization approaches provided by the R statistical computing environment. RESULTS: This manuscript describes the plethy package which is an R/Bioconductor framework for pre-processing and analysis of plethysmography data with emphasis on larger scale longitudinal experiments. The plethy package was designed to facilitate quality control and exploratory data analysis. We provide a demonstration of the features of plethy using a dataset assessing the respiratory effects over time of SARS and Influenza infection in mice. CONCLUSION: The plethy package provides functionality for users to import, perform quality assessment and exploratory data analysis in a manner that allows interoperability with existing modelling tools. Our package is implemented in R and is freely available as part of the Bioconductor project http://www.bioconductor.org/packages/release/bioc/html/plethy.html. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0547-7) contains supplementary material, which is available to authorized users.",2015 Apr 29,"['Bottomly, Daniel', 'Wilmot, Beth', 'McWeeney, Shannon K']",BMC Bioinformatics,,,True
8f240d93eda7d04def440b93acf64e41910f4e7c,PMC,plethy: management of whole body plethysmography data in R,http://dx.doi.org/10.1186/s12859-015-0547-7,PMC4434826,25924931,CC BY,"BACKGROUND: Characterization of respiratory phenotypes can enhance complex trait and genomic studies involving allergic/autoimmune and infectious diseases. Many aspects of respiration can be measured using devices known as plethysmographs that can measure thoracic movement. One such approach (the Buxco platform) performs unrestrained whole body plethysmography on mice which infers thoracic movements from pressure differences from the act of inhalation and exhalation. While proprietary software is available to perform basic statistical analysis as part of machine’s bundled software, it is desirable to be able to incorporate these analyses into high-throughput pipelines and integrate them with other data types, as well as leverage the wealth of analytic and visualization approaches provided by the R statistical computing environment. RESULTS: This manuscript describes the plethy package which is an R/Bioconductor framework for pre-processing and analysis of plethysmography data with emphasis on larger scale longitudinal experiments. The plethy package was designed to facilitate quality control and exploratory data analysis. We provide a demonstration of the features of plethy using a dataset assessing the respiratory effects over time of SARS and Influenza infection in mice. CONCLUSION: The plethy package provides functionality for users to import, perform quality assessment and exploratory data analysis in a manner that allows interoperability with existing modelling tools. Our package is implemented in R and is freely available as part of the Bioconductor project http://www.bioconductor.org/packages/release/bioc/html/plethy.html. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0547-7) contains supplementary material, which is available to authorized users.",2015 Apr 29,"['Bottomly, Daniel', 'Wilmot, Beth', 'McWeeney, Shannon K']",BMC Bioinformatics,,,True
29621887690af716dac0c244eeb95bce74fa8755,PMC,Mast Cells and Influenza A Virus: Association with Allergic Responses and Beyond,http://dx.doi.org/10.3389/fimmu.2015.00238,PMC4435071,26042121,CC BY,"Influenza A virus (IAV) is a widespread infectious agent commonly found in mammalian and avian species. In humans, IAV is a respiratory pathogen that causes seasonal infections associated with significant morbidity in young and elderly populations, and has a large economic impact. Moreover, IAV has the potential to cause both zoonotic spillover infection and global pandemics, which have significantly greater morbidity and mortality across all ages. The pathology associated with these pandemic and spillover infections appear to be the result of an excessive inflammatory response leading to severe lung damage, which likely predisposes the lungs for secondary bacterial infections. The lung is protected from pathogens by alveolar epithelial cells, endothelial cells, tissue resident alveolar macrophages, dendritic cells, and mast cells. The importance of mast cells during bacterial and parasitic infections has been extensively studied; yet, the role of these hematopoietic cells during viral infections is only beginning to emerge. Recently, it has been shown that mast cells can be directly activated in response to IAV, releasing mediators such histamine, proteases, leukotrienes, inflammatory cytokines, and antiviral chemokines, which participate in the excessive inflammatory and pathological response observed during IAV infections. In this review, we will examine the relationship between mast cells and IAV, and discuss the role of mast cells as a potential drug target during highly pathological IAV infections. Finally, we proposed an emerging role for mast cells in other viral infections associated with significant host pathology.",2015 May 18,"['Graham, Amy C.', 'Temple, Rachel M.', 'Obar, Joshua J.']",Front Immunol,,,True
7de0d0ac71e79cba5b50ed89303cae6d89bb0130,PMC,Multiplexed Component Analysis to Identify Genes Contributing to the Immune Response during Acute SIV Infection,http://dx.doi.org/10.1371/journal.pone.0126843,PMC4436129,25984721,CC BY,"Immune response genes play an important role during acute HIV and SIV infection. Using an SIV macaque model of AIDS and CNS disease, our overall goal was to assess how the expression of genes associated with immune and inflammatory responses are longitudinally changed in different organs or cells during SIV infection. To compare RNA expression of a panel of 88 immune-related genes across time points and among three tissues – spleen, mesenteric lymph nodes (MLN) and peripheral blood mononuclear cells (PBMC) – we designed a set of Nanostring probes. To identify significant genes during acute SIV infection and to investigate whether these genes are tissue-specific or have global roles, we introduce a novel multiplexed component analysis (MCA) method. This combines multivariate analysis methods with multiple preprocessing methods to create a set of 12 “judges”; each judge emphasizes particular types of change in gene expression to which cells could respond, for example, the absolute or relative size of expression change from baseline. Compared to bivariate analysis methods, our MCA method improved classification rates. This analysis allows us to identify three categories of genes: (a) consensus genes likely to contribute highly to the immune response; (b) genes that would contribute highly to the immune response only if certain assumptions are met – e.g. that the cell responds to relative expression change rather than absolute expression change; and (c) genes whose contribution to immune response appears to be modest. We then compared the results across the three tissues of interest; some genes are consistently highly-contributing in all tissues, while others are specific for certain tissues. Our analysis identified CCL8, CXCL10, CXCL11, MxA, OAS2, and OAS1 as top contributing genes, all of which are stimulated by type I interferon. This suggests that the cytokine storm during acute SIV infection is a systemic innate immune response against viral replication. Furthermore, these genes have approximately equal contributions to all tissues, making them possible candidates to be used as non-invasive biomarkers in studying PBMCs instead of MLN and spleen during acute SIV infection experiments. We identified clusters of genes that co-vary together and studied their correlation with regard to other gene clusters. We also developed novel methods to faithfully visualize multi-gene correlations on two-dimensional polar plots, and to visualize tissue specificity of gene expression responses.",2015 May 18,"['Hosseini, Iraj', 'Gama, Lucio', 'Mac Gabhann, Feilim']",PLoS One,,,True
a3a2b5d607691f30dd1b1baeca0e41817e2fde86,PMC,Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice,http://dx.doi.org/10.1155/2015/765490,PMC4436448,26075259,CC BY,"Dickkopf-1 (DKK1), a secretory inhibitor of canonical Wnt signaling, plays a critical role in certain bone loss diseases. Studies have shown that serum levels of DKK1 are significantly higher in rheumatoid arthritis (RA) patients and are correlated with the severity of the disease, which indicates the possibility that bone erosion in RA may be inhibited by neutralizing the biological activity of DKK1. In this study, we selected a panel of twelve peptides using the software DNASTAR 7.1 and screened high affinity and immunogenicity epitopes in vitro and in vivo assays. Furthermore, we optimized four B cell epitopes to design a novel DKK1 multiepitope DNA vaccine and evaluated its bone protective effects in collagen-induced arthritis (CIA), a mouse model of RA. High level expression of the designed vaccine was measured in supernatant of COS7 cells. In addition, intramuscular immunization of BALB/c mice with this vaccine was also highly expressed and sufficient to induce the production of long-term IgG, which neutralized natural DKK1 in vivo. Importantly, this vaccine significantly attenuated bone erosion in CIA mice compared with positive control mice. These results provide evidence for the development of a DNA vaccine targeted against DKK1 to attenuate bone erosion.",2015 May 5,"['Zhang, Xiaoqing', 'Liu, Sibo', 'Li, Shentao', 'Du, Yuxuan', 'Dou, Yunpeng', 'Li, Zhanguo', 'Yuan, Huihui', 'Zhao, Wenming']",Biomed Res Int,,,True
5934262a2b502aa5c1312dca72507395da00ccbe,PMC,Neopterin in Diagnosis and Monitoring of Infectious Diseases,http://dx.doi.org/10.1155/2013/196432,PMC4437389,26317013,CC BY,"Neopterin is produced by activated monocytes, macrophages, and dendritic cells upon stimulation by interferon gamma produced by T-lymphocytes. Quantification of neopterin in body fluids has been achieved by standard high-performance liquid chromatography, radioimmunoassays, and enzyme-linked immunosorbent assays. Neopterin levels predict HIV-related mortality more efficiently than clinical manifestations. Successful highly active antiretroviral therapy is associated with a decrease in neopterin levels. Elevated neopterin levels were associated with hepatitis by hepatitis A, B, and C viruses. Serum neopterin levels were found to be a predictor of response to treatment of chronic HCV infection with pegylated interferon combined with ribavirin. Neopterin levels of patients with pulmonary tuberculosis were found to be higher in patients with more extensive radiological changes. Elimination of blood donors with elevated neopterin levels to reduce risk of transmission of infections with known and unknown viral pathogens has been undertaken. Neopterin measurement is hereby more cost effective but less sensitive than screening using polymerase chain reaction based assays. In conclusion neopterin is a nonspecific marker of activated T-helper cell 1 dominated immune response. It may be a useful marker for monitoring of infectious disease activity during treatment and for more accurate estimation of extent of disease and prognosis.",2013 Dec 8,"Eisenhut, Michael",J Biomark,,,True
b5af7319ee1fd5e9cc3cf8c5836b19a408ac519b,PMC,Inhibition of a Putative Dihydropyrimidinase from Pseudomonas aeruginosa PAO1 by Flavonoids and Substrates of Cyclic Amidohydrolases,http://dx.doi.org/10.1371/journal.pone.0127634,PMC4437985,25993634,CC BY,"Dihydropyrimidinase is a member of the cyclic amidohydrolase family, which also includes allantoinase, dihydroorotase, hydantoinase, and imidase. These metalloenzymes possess very similar active sites and may use a similar mechanism for catalysis. However, whether the substrates and inhibitors of other cyclic amidohydrolases can inhibit dihydropyrimidinase remains unclear. This study investigated the inhibition of dihydropyrimidinase by flavonoids and substrates of other cyclic amidohydrolases. Allantoin, dihydroorotate, 5-hydantoin acetic acid, acetohydroxamate, orotic acid, and 3-amino-1,2,4-triazole could slightly inhibit dihydropyrimidinase, and the IC(50) values of these compounds were within the millimolar range. The inhibition of dihydropyrimidinase by flavonoids, such as myricetin, quercetin, kaempferol, galangin, dihydromyricetin, and myricitrin, was also investigated. Some of these compounds are known as inhibitors of allantoinase and dihydroorotase. Although the inhibitory effects of these flavonoids on dihydropyrimidinase were substrate-dependent, dihydromyricetin significantly inhibited dihydropyrimidinase with IC(50) values of 48 and 40 μM for the substrates dihydrouracil and 5-propyl-hydantoin, respectively. The results from the Lineweaver−Burk plot indicated that dihydromyricetin was a competitive inhibitor. Results from fluorescence quenching analysis indicated that dihydromyricetin could form a stable complex with dihydropyrimidinase with the K (d) value of 22.6 μM. A structural study using PatchDock showed that dihydromyricetin was docked in the active site pocket of dihydropyrimidinase, which was consistent with the findings from kinetic and fluorescence studies. This study was the first to demonstrate that naturally occurring product dihydromyricetin inhibited dihydropyrimidinase, even more than the substrate analogs (>3 orders of magnitude). These flavonols, particularly myricetin, may serve as drug leads and dirty drugs (for multiple targets) for designing compounds that target several cyclic amidohydrolases.",2015 May 19,"Huang, Cheng-Yang",PLoS One,,,True
a4efe5912760797318110dec69b255d743f0f0bd,PMC,CXCR2 is essential for cerebral endothelial activation and leukocyte recruitment during neuroinflammation,http://dx.doi.org/10.1186/s12974-015-0316-6,PMC4438521,25990934,CC BY,"BACKGROUND: Chemokines and chemokine receptors cooperate to promote immune cell recruitment to the central nervous system (CNS). In this study, we investigated the roles of CXCR2 and CXCL1 in leukocyte recruitment to the CNS using a murine model of neuroinflammation. METHODS: Wild-type (WT), CXCL1(−/−), and CXCR2(−/−) mice each received an intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). Esterase staining and intravital microscopy were performed to examine neutrophil recruitment to the brain. To assess endothelial activation in these mice, the expression of adhesion molecules was measured via quantitative real-time polymerase chain reaction (PCR) and Western blotting. To identify the cellular source of functional CXCR2, chimeric mice were generated by transferring bone marrow cells between the WT and CXCR2(−/−) mice. RESULTS: Expression levels of the chemokines CXCL1, CXCL2, and CXCL5 were significantly increased in the brain following the i.c.v. injection of LPS. CXCR2 or CXCL1 deficiency blocked neutrophil infiltration and leukocyte recruitment in the cerebral microvessels. In the CXCR2(−/−) and CXCL1(−/−) mice, the cerebral endothelial expression of adhesion molecules such as P-selectin and VCAM-1 was dramatically reduced. Furthermore, the bone marrow transfer experiments demonstrated that CXCR2 expression on CNS-residing cells is essential for cerebral endothelial activation and leukocyte recruitment. Compared with microglia, cultured astrocytes secreted a much higher level of CXCL1 in vitro. Astrocyte culture conditioned medium significantly increased the expression of VCAM-1 and ICAM-1 in cerebral endothelial cells in a CXCR2-dependent manner. Additionally, CXCR2 messenger RNA (mRNA) expression in cerebral endothelial cells but not in microglia or astrocytes was increased following tumor necrosis factor-α (TNF-α) stimulation. The intravenous injection of the CXCR2 antagonist SB225002 significantly inhibited endothelial activation and leukocyte recruitment to cerebral microvessels. CONCLUSIONS: CXCL1 secreted by astrocytes and endothelial CXCR2 play essential roles in cerebral endothelial activation and subsequent leukocyte recruitment during neuroinflammation.",2015 May 21,"['Wu, Fengjiao', 'Zhao, Yawei', 'Jiao, Tian', 'Shi, Dongyan', 'Zhu, Xingxing', 'Zhang, Mingshun', 'Shi, Meiqing', 'Zhou, Hong']",J Neuroinflammation,,,True
a093f4ef60a47e5419181f6826ad4a45af198056,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,True
400d460a24bbc4165f5185484aa02807725d8d2c,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,False
f098138b4f4c09010693258de4211f968b8b4481,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,False
e4cecbeafb7ae61db981f0a3d22e07e55a41166b,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,False
0f316dba030fe5b826013e64b2b458fab695c9fb,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,False
8fd4e79d6b5ecf52f1649507df71ca75b64fcd34,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,False
2d1caa039267b86b3d4c4070dd72e0a389d70bf2,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,False
2002a6ed2eeda2b94a2db6292ef19098088f2f04,PMC,"Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections",http://dx.doi.org/10.1371/journal.ppat.1004900,PMC4438980,25993603,CC BY,"Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential.",2015 May 20,"['Stenglein, Mark D.', 'Jacobson, Elliott R.', 'Chang, Li-Wen', 'Sanders, Chris', 'Hawkins, Michelle G.', 'Guzman, David S-M.', 'Drazenovich, Tracy', 'Dunker, Freeland', 'Kamaka, Elizabeth K.', 'Fisher, Debbie', 'Reavill, Drury R.', 'Meola, Linda F.', 'Levens, Gregory', 'DeRisi, Joseph L.']",PLoS Pathog,,,False
3236c24e4656add3fbf17ed686d2b7c73bb52de9,PMC,Detection of Acute HIV-1 Infection by RT-LAMP,http://dx.doi.org/10.1371/journal.pone.0126609,PMC4439053,25993381,CC0,"A rapid, cost-effective diagnostic test for the detection of acute HIV-1 infection is highly desired. Isothermal amplification techniques, such as reverse-transcription loop-mediated isothermal amplification (RT-LAMP), exhibit characteristics that are ideal for the development of a rapid nucleic acid amplification test (NAAT) because they are quick, easy to perform and do not require complex, dedicated equipment and laboratory space. In this study, we assessed the ability of the HIV-1 RT-LAMP assay to detect acute HIV infection as compared to a representative rapid antibody test and several FDA-approved laboratory-based assays. The HIV-1 RT-LAMP assay detected seroconverting individuals one to three weeks earlier than a rapid HIV antibody test and up to two weeks earlier than a lab-based antigen/antibody (Ag/Ab) combo enzyme immunoassay (EIA). RT-LAMP was not as sensitive as a lab-based qualitative RNA assay, which could be attributed to the significantly smaller nucleic acid input volume. To our knowledge, this is the first demonstration of detecting acute HIV infection using the RT-LAMP assay. The availability of a rapid NAAT, such as the HIV-1 RT-LAMP assay, at the point of care (POC) or in laboratories that do not have access to large platform NAAT could increase the percentage of individuals who receive an acute HIV infection status or confirmation of their HIV status, while immediately linking them to counseling and medical care. In addition, early knowledge of HIV status could lead to reduced high-risk behavior at a time when individuals are at a higher risk for transmitting the virus.",2015 May 20,"['Rudolph, Donna L.', 'Sullivan, Vickie', 'Owen, S. Michele', 'Curtis, Kelly A.']",PLoS One,,,True
9df0801be110f632c616bf9e91cb72d59383b086,PMC,Is Tuberculosis Treatment Really Free in China? A Study Comparing Two Areas with Different Management Models,http://dx.doi.org/10.1371/journal.pone.0126770,PMC4439067,25993411,CC BY,"OBJECTIVE: China has implemented a free-service policy for tuberculosis. However, patients still have to pay a substantial proportion of their annual income for treatment of this disease. This study describes the economic burden on patients with tuberculosis; identifies related factors by comparing two areas with different management models; and provides policy recommendation for tuberculosis control reform in China. METHODS: There are three tuberculosis management models in China: the tuberculosis dispensary model, specialist model and integrated model. We selected Zhangjiagang (ZJG) and Taixing (TX) as the study sites, which correspond to areas implementing the integrated model and dispensary model, respectively. Patients diagnosed and treated for tuberculosis since January 2010 were recruited as study subjects. A total of 590 patients (316 patients from ZJG and 274 patients from TX) were interviewed with a response rate of 81%. The economic burden attributed to tuberculosis, including direct costs and indirect costs, was estimated and compared between the two study sites. The Mann-Whitney U Test was used to compare the cost differences between the two groups. Potential factors related to the total out-of-pocket costs were analyzed based on a step-by-step multivariate linear regression model after the logarithmic transformation of the costs. RESULTS: The average (median, interquartile range) total cost was 18793.33 (9965, 3200-24400) CNY for patients in ZJG, which was significantly higher than for patients in TX (mean: 6598.33, median: 2263, interquartile range: 983–6688) (Z = 10.42, P < 0.001). After excluding expenses covered by health insurance, the average out-of-pocket costs were 14304.4 CNY in ZJG and 5639.2 CNY in TX. Based on the multivariable linear regression analysis, factors related to the total out-of-pocket costs were study site, age, number of clinical visits, residence, diagnosis delay, hospitalization, intake of liver protective drugs and use of the second-line drugs. CONCLUSION: Under the current “free of diagnosis and treatment” policy, the financial burden remains heavy on tuberculosis patients. Policy makers need to consider appropriate steps to lessen the burden of out-of-pocket costs for tuberculosis patients in China and how best to improve service delivery for poor patients.",2015 May 20,"['Qiu, Sangsang', 'Pan, Hongqiu', 'Zhang, Simin', 'Peng, Xianzhen', 'Zheng, Xianzhi', 'Xu, Guisheng', 'Wang, Min', 'Wang, Jianming', 'Lu, Hui']",PLoS One,,,True
bb61779140755a7d48b8d5ff6d848a07977b4af3,PMC,Correction: Chinese Social Media Reaction to Information about 42 Notifiable Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0129525,PMC4439074,25992906,CC BY,,2015 May 20,,PLoS One,,,False
d569871d337077bcb21c8c19fde422b0bca8e0c8,PMC,Viral Etiology of Chronic Obstructive Pulmonary Disease Exacerbations during the A/H1N1pdm09 Pandemic and Postpandemic Period,http://dx.doi.org/10.1155/2015/560679,PMC4439490,26064118,CC BY,"Viral infections are one of the main causes of acute exacerbations of chronic obstructive pulmonary disease (AE-COPD). Emergence of A/H1N1pdm influenza virus in the 2009 pandemic changed the viral etiology of exacerbations that were reported before the pandemic. The aim of this study was to describe the etiology of respiratory viruses in 195 Spanish patients affected by AE-COPD from the pandemic until the 2011-12 influenza epidemic. During the study period (2009–2012), respiratory viruses were identified in 48.7% of samples, and the proportion of viral detections in AE-COPD was higher in patients aged 30–64 years than ≥65 years. Influenza A viruses were the pathogens most often detected during the pandemic and the following two influenza epidemics in contradistinction to human rhino/enteroviruses that were the main viruses causing AE-COPD before the pandemic. The probability of influenza virus detection was 2.78-fold higher in patients who are 30–64 years old than those ≥65. Most respiratory samples were obtained during the pandemic, but the influenza detection rate was higher during the 2011-12 epidemic. There is a need for more accurate AE-COPD diagnosis, emphasizing the role of respiratory viruses. Furthermore, diagnosis requires increased attention to patient age and the characteristics of each influenza epidemic.",2015 May 7,"['Sanz, Ivan', 'Tamames, Sonia', 'Rojo, Silvia', 'Justel, Mar', 'Lozano, José Eugenio', 'Disdier, Carlos', 'Vega, Tomás', 'Ortiz de Lejarazu, Raúl']",Adv Virol,,,True
0bcbf352d92ce90e1c2595fb458ded32b45002a0,PMC,Human seroprevalence indicating hantavirus infections in tropical rainforests of Côte d’Ivoire and Democratic Republic of Congo,http://dx.doi.org/10.3389/fmicb.2015.00518,PMC4439549,26052326,CC BY,"Hantaviruses are members of the Bunyaviridae family carried by small mammals and causing human hemorrhagic fevers worldwide. In Western Africa, where a variety of hemorrhagic fever viruses occurs, indigenous hantaviruses have been molecularly found in animal reservoirs such as rodents, shrews, and bats since 2006. To investigate the human contact to hantaviruses carried by these hosts and to assess the public health relevance of hantaviruses for humans living in the tropical rainforest regions of Western and Central Africa, we performed a cross-sectional seroprevalence study in the region of Taï National Park in Côte d’Ivoire and the Bandundu region near the Salonga National Park in the Democratic Republic (DR) of Congo. Serum samples were initially screened with enzyme-linked immunosorbent assays using nucleoproteins of several hantaviruses as diagnostic antigens. Positive results were confirmed by Western blotting and immunofluorescence testing. Seroprevalence rates of 3.9% (27/687) and 2.4% (7/295), respectively, were found in the investigated regions in Côte d’Ivoire and the DR Congo. In Côte d’Ivoire, this value was significantly higher than the seroprevalence rates previously reported from the neighboring country Guinea as well as from South Africa. Our study indicates an exposure of humans to hantaviruses in West and Central African tropical rainforest areas. In order to pinpoint the possible existence and frequency of clinical disease caused by hantaviruses in this region of the world, systematic investigations of patients with fever and renal or respiratory symptoms are required.",2015 May 21,"['Witkowski, Peter T.', 'Leendertz, Siv A. J.', 'Auste, Brita', 'Akoua-Koffi, Chantal', 'Schubert, Grit', 'Klempa, Boris', 'Muyembe-Tamfum, Jean-Jacques', 'Karhemere, Stomy', 'Leendertz, Fabian H.', 'Krüger, Detlev H.']",Front Microbiol,,,True
f9410459142b63fb34eac0375dda7d9b6460b3fe,PMC,Persistent Foot-and-Mouth Disease Virus Infection in the Nasopharynx of Cattle; Tissue-Specific Distribution and Local Cytokine Expression,http://dx.doi.org/10.1371/journal.pone.0125698,PMC4440813,25996935,CC0,"Tissues obtained post-mortem from cattle persistently infected with foot-and-mouth disease virus (FMDV) were analyzed to characterize the tissue-specific localization of FMDV and partial transcriptome profiles for selected immunoregulatory cytokines. Analysis of 28 distinct anatomic sites from 21 steers infected with FMDV serotype A, O or SAT2, had the highest prevalence of overall viral detection in the dorsal nasopharynx (80.95%) and dorsal soft palate (71.43%). FMDV was less frequently detected in laryngeal mucosal tissues, oropharyngeal mucosal sites, and lymph nodes draining the pharynx. Immunomicroscopy indicated that within persistently infected mucosal tissues, FMDV antigens were rarely detectable within few epithelial cells in regions of mucosa-associated lymphoid tissue (MALT). Transcriptome analysis of persistently infected pharyngeal tissues by qRT-PCR for 14 cytokine genes indicated a general trend of decreased mRNA levels compared to uninfected control animals. Although, statistically significant differences were not observed, greatest suppression of relative expression (RE) was identified for IP-10 (RE = 0.198), IFN-β (RE = 0.269), IL-12 (RE = 0.275), and IL-2 (RE = 0.312). Increased relative expression was detected for IL-6 (RE = 2.065). Overall, this data demonstrates that during the FMDV carrier state in cattle, viral persistence is associated with epithelial cells of the nasopharynx in the upper respiratory tract and decreased levels of mRNA for several immunoregulatory cytokines in the infected tissues.",2015 May 21,"['Pacheco, Juan M.', 'Smoliga, George R.', 'O’Donnell, Vivian', 'Brito, Barbara P.', 'Stenfeldt, Carolina', 'Rodriguez, Luis L.', 'Arzt, Jonathan']",PLoS One,,,True
a9f21b4c08ef6cf4b7553c5666b4102d0c984243,PMC,Broad-spectrum antiviral agents,http://dx.doi.org/10.3389/fmicb.2015.00517,PMC4440912,26052325,CC BY,"Development of highly effective, broad-spectrum antiviral agents is the major objective shared by the fields of virology and pharmaceutics. Antiviral drug development has focused on targeting viral entry and replication, as well as modulating cellular defense system. High throughput screening of molecules, genetic engineering of peptides, and functional screening of agents have identified promising candidates for development of optimal broad-spectrum antiviral agents to intervene in viral infection and control viral epidemics. This review discusses current knowledge, prospective applications, opportunities, and challenges in the development of broad-spectrum antiviral agents.",2015 May 22,"['Zhu, Jun-Da', 'Meng, Wen', 'Wang, Xiao-Jia', 'Wang, Hwa-Chain R.']",Front Microbiol,,,True
ae99d270c1b2d2307c4375fecde1a037c263b507,PMC,"Complete Genome Sequence of a Porcine Epidemic Diarrhea Virus from a Novel Outbreak in Belgium, January 2015",http://dx.doi.org/10.1128/genomeA.00506-15,PMC4440965,25999551,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a member of the family Coronaviridae and can cause severe outbreaks of diarrhea in piglets from different age groups. Here, we report the complete genome sequence (28,028 nt) of a PEDV strain isolated during a novel outbreak in Belgium.",2015 May 21,"['Theuns, Sebastiaan', 'Conceição-Neto, Nádia', 'Christiaens, Isaura', 'Zeller, Mark', 'Desmarets, Lowiese M. B.', 'Roukaerts, Inge D. M.', 'Acar, Delphine D.', 'Heylen, Elisabeth', 'Matthijnssens, Jelle', 'Nauwynck, Hans J.']",Genome Announc,,,True
5a85cf34eee367f1a73ac62a05779d4c815dc767,PMC,Interactions of Francisella tularensis with Alveolar Type II Epithelial Cells and the Murine Respiratory Epithelium,http://dx.doi.org/10.1371/journal.pone.0127458,PMC4444194,26010977,CC BY,"Francisella tularensis is classified as a Tier 1 select agent by the CDC due to its low infectious dose and the possibility that the organism can be used as a bioweapon. The low dose of infection suggests that Francisella is unusually efficient at evading host defenses. Although ~50 cfu are necessary to cause human respiratory infection, the early interactions of virulent Francisella with the lung environment are not well understood. To provide additional insights into these interactions during early Francisella infection of mice, we performed TEM analysis on mouse lungs infected with F. tularensis strains Schu S4, LVS and the O-antigen mutant Schu S4 waaY::TrgTn. For all three strains, the majority of the bacteria that we could detect were observed within alveolar type II epithelial cells at 16 hours post infection. Although there were no detectable differences in the amount of bacteria within an infected cell between the three strains, there was a significant increase in the amount of cellular debris observed in the air spaces of the lungs in the Schu S4 waaY::TrgTn mutant compared to either the Schu S4 or LVS strain. We also studied the interactions of Francisella strains with human AT-II cells in vitro by characterizing the ability of these three strains to invade and replicate within these cells. Gentamicin assay and confocal microscopy both confirmed that F. tularensis Schu S4 replicated robustly within these cells while F. tularensis LVS displayed significantly lower levels of growth over 24 hours, although the strain was able to enter these cells at about the same level as Schu S4 (1 organism per cell), as determined by confocal imaging. The Schu S4 waaY::TrgTn mutant that we have previously described as attenuated for growth in macrophages and mouse virulence displayed interesting properties as well. This mutant induced significant airway inflammation (cell debris) and had an attenuated growth phenotype in the human AT-II cells. These data extend our understanding of early Francisella infection by demonstrating that Francisella enter significant numbers of AT-II cells within the lung and that the capsule and LPS of wild type Schu S4 helps prevent murine lung damage during infection. Furthermore, our data identified that human AT-II cells allow growth of Schu S4, but these same cells supported poor growth of the attenuated LVS strain in vitro. Collectively, these data further our understanding of the role of AT-II cells in Francisella infections.",2015 May 26,"['Faron, Matthew', 'Fletcher, Joshua R.', 'Rasmussen, Jed A.', 'Apicella, Michael A.', 'Jones, Bradley D.']",PLoS One,,,True
4cd92be2bf6b804588415da689ae6afa8ef97099,PMC,Efficiency of Airborne Sample Analysis Platform (ASAP) bioaerosol sampler for pathogen detection,http://dx.doi.org/10.3389/fmicb.2015.00512,PMC4444837,26074900,CC BY,"The threat of bioterrorism and pandemics has highlighted the urgency for rapid and reliable bioaerosol detection in different environments. Safeguarding against such threats requires continuous sampling of the ambient air for pathogen detection. In this study we investigated the efficacy of the Airborne Sample Analysis Platform (ASAP) 2800 bioaerosol sampler to collect representative samples of air and identify specific viruses suspended as bioaerosols. To test this concept, we aerosolized an innocuous replication-defective bovine adenovirus serotype 3 (BAdV3) in a controlled laboratory environment. The ASAP efficiently trapped the surrogate virus at 5 × 10(3) plaque-forming units (p.f.u.) [2 × 10(5) genome copy equivalent] concentrations or more resulting in the successful detection of the virus using quantitative PCR. These results support the further development of ASAP for bioaerosol pathogen detection.",2015 May 27,"['Sharma, Anurag', 'Clark, Elizabeth', 'McGlothlin, James D.', 'Mittal, Suresh K.']",Front Microbiol,,,True
5d5edffd3b3213b480c77b6a06949a8a88618b69,PMC,Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves,http://dx.doi.org/10.1186/1471-2164-15-1164,PMC4445561,25534905,CC BY,"BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Neibergs, Holly L', 'Seabury, Christopher M', 'Wojtowicz, Andrzej J', 'Wang, Zeping', 'Scraggs, Erik', 'Kiser, Jennifer N', 'Neupane, Mahesh', 'Womack, James E', 'Eenennaam, Alison Van', 'Hagevoort, Gerald Robert', 'Lehenbauer, Terry W', 'Aly, Sharif', 'Davis, Jessica', 'Taylor, Jeremy F', None]",BMC Genomics,,,True
f02e28bfe40a510818fba3cc0adc91d7dd1c3af3,PMC,Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves,http://dx.doi.org/10.1186/1471-2164-15-1164,PMC4445561,25534905,CC BY,"BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Neibergs, Holly L', 'Seabury, Christopher M', 'Wojtowicz, Andrzej J', 'Wang, Zeping', 'Scraggs, Erik', 'Kiser, Jennifer N', 'Neupane, Mahesh', 'Womack, James E', 'Eenennaam, Alison Van', 'Hagevoort, Gerald Robert', 'Lehenbauer, Terry W', 'Aly, Sharif', 'Davis, Jessica', 'Taylor, Jeremy F', None]",BMC Genomics,,,False
d057621b1ac0ac1b494345f20d432f6f7a78760d,PMC,Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves,http://dx.doi.org/10.1186/1471-2164-15-1164,PMC4445561,25534905,CC BY,"BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Neibergs, Holly L', 'Seabury, Christopher M', 'Wojtowicz, Andrzej J', 'Wang, Zeping', 'Scraggs, Erik', 'Kiser, Jennifer N', 'Neupane, Mahesh', 'Womack, James E', 'Eenennaam, Alison Van', 'Hagevoort, Gerald Robert', 'Lehenbauer, Terry W', 'Aly, Sharif', 'Davis, Jessica', 'Taylor, Jeremy F', None]",BMC Genomics,,,False
3258f0c4d9a0a3e68fabba3bd166a150c43ba6eb,PMC,Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves,http://dx.doi.org/10.1186/1471-2164-15-1164,PMC4445561,25534905,CC BY,"BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Neibergs, Holly L', 'Seabury, Christopher M', 'Wojtowicz, Andrzej J', 'Wang, Zeping', 'Scraggs, Erik', 'Kiser, Jennifer N', 'Neupane, Mahesh', 'Womack, James E', 'Eenennaam, Alison Van', 'Hagevoort, Gerald Robert', 'Lehenbauer, Terry W', 'Aly, Sharif', 'Davis, Jessica', 'Taylor, Jeremy F', None]",BMC Genomics,,,False
fc366b1091121f8885d1d84e605c2353f2757c4c,PMC,Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves,http://dx.doi.org/10.1186/1471-2164-15-1164,PMC4445561,25534905,CC BY,"BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Neibergs, Holly L', 'Seabury, Christopher M', 'Wojtowicz, Andrzej J', 'Wang, Zeping', 'Scraggs, Erik', 'Kiser, Jennifer N', 'Neupane, Mahesh', 'Womack, James E', 'Eenennaam, Alison Van', 'Hagevoort, Gerald Robert', 'Lehenbauer, Terry W', 'Aly, Sharif', 'Davis, Jessica', 'Taylor, Jeremy F', None]",BMC Genomics,,,False
d4faf81a864d265824ca6417fafec11f3b40ab15,PMC,Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves,http://dx.doi.org/10.1186/1471-2164-15-1164,PMC4445561,25534905,CC BY,"BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Neibergs, Holly L', 'Seabury, Christopher M', 'Wojtowicz, Andrzej J', 'Wang, Zeping', 'Scraggs, Erik', 'Kiser, Jennifer N', 'Neupane, Mahesh', 'Womack, James E', 'Eenennaam, Alison Van', 'Hagevoort, Gerald Robert', 'Lehenbauer, Terry W', 'Aly, Sharif', 'Davis, Jessica', 'Taylor, Jeremy F', None]",BMC Genomics,,,False
b68d33bbec8af949490bf52a5b8dd215c2b37590,PMC,Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves,http://dx.doi.org/10.1186/1471-2164-15-1164,PMC4445561,25534905,CC BY,"BACKGROUND: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated. RESULTS: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined. CONCLUSIONS: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1164) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Neibergs, Holly L', 'Seabury, Christopher M', 'Wojtowicz, Andrzej J', 'Wang, Zeping', 'Scraggs, Erik', 'Kiser, Jennifer N', 'Neupane, Mahesh', 'Womack, James E', 'Eenennaam, Alison Van', 'Hagevoort, Gerald Robert', 'Lehenbauer, Terry W', 'Aly, Sharif', 'Davis, Jessica', 'Taylor, Jeremy F', None]",BMC Genomics,,,True
12aa5eeb50296d810121cc1b2f87f053c39ce204,PMC,Single amino acid substitution (G42E) in the receptor binding domain of mouse mammary tumour virus envelope protein facilitates infection of non-murine cells in a transferrin receptor 1-independent manner,http://dx.doi.org/10.1186/s12977-015-0168-2,PMC4445801,25980759,CC BY,"BACKGROUND: Mouse mammary tumour virus (MMTV) is a betaretrovirus that infects rodent cells and uses mouse tranferrin receptor 1 (TfR1) for cell entry. Several MMTV strains have been shown to productively infect, in addition to murine cells, various heterologous cell lines including those of human origin, albeit less efficiently than murine cells. Furthermore, there have been reports that the continued passage of MMTV in heterologous cell lines gives rise to novel variants that are able to infect naive non-murine cells with higher efficiency than the parental virus. RESULTS: We show that MMTV(C3H), like other MMTV strains, that had undergone a number of replication cycles in non-murine cells displayed an increased replication kinetic, as compared to parental virus, when applied on naive human cells. Sequence analysis of several replication kinetic variants and the parental virus, together with calculation of the ratio of non-synonymous to synonymous mutations at individual codons, revealed that several regions within the viral genome were under strong positive selection pressure during viral replication in human cells. The mutation responsible, at least in part, for the phenotypic change was subsequently mapped to the segment of env encoding the receptor binding site (F(40)HGFR(44)). Introduction of the identified mutation, leading to single amino acid substitution (G42E), into egfp-containing recombinant MMTV virions enhanced their ability to bind to and infect human cells. Interestingly, neither the replication kinetic mutant nor the parental virus required human TfR1 for infection. Knock-out of TFR1 gene from the human genome did not decrease the susceptibility of Hs578T cells to virus infection. Furthermore, the expression of human TfR1, in contrast to mouse TfR1, did not enhance the susceptibility of MMTV-resistant Chinese hamster ovary cells. Thus, human TfR1 is dispensable for infection and another cell surface molecule mediates the MMTV entry into human cells. CONCLUSION: Taken together, our data explain the mechanism enabling MMTV to form ‘host-range variants’ in non-murine cells that has been known for a long time, the basis of which remained obscure. Our findings may expand our understanding of how viruses gain capability to cross species-specific barriers to infect new hosts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-015-0168-2) contains supplementary material, which is available to authorized users.",2015 May 16,"['Konstantoulas, Constantine James', 'Lamp, Benjamin', 'Rumenapf, Tillman Hans', 'Indik, Stanislav']",Retrovirology,,,True
f223f427cbdd077ec84931fad74fb3a7a46fbc67,PMC,Recent Advances in Dipeptidyl-Peptidase-4 Inhibition Therapy: Lessons from the Bench and Clinical Trials,http://dx.doi.org/10.1155/2015/606031,PMC4446505,26075284,CC BY,"DPP4 inhibitors (DPP4i) are a class of newly developed antidiabetic drugs which preserve incretin hormones and promote postprandial insulin secretion. Although the cardiovascular effect of DPP4 inhibition has been substantially studied, the exact role of DPP4 in cardiovascular disease especially in humans remains elusive. Previous small studies and meta-analyses have suggested a benefit in both surrogate outcomes and cardiovascular events for these agents. However, there was growing evidence in recent years questioning the cardioprotective effect of DPP4i. Further, a signal of heart failure hospitalization in a recent large scale clinical trial SAVOR-TIMI 53 has called into question the safety of these agents and their utility in the treatment of cardiovascular disease. In this review, we will revisit the physiologic function of DPP4 and discuss its role in cardiometabolic disease based on recent experimental and clinical studies.",2015 May 14,"['Zhong, Jixin', 'Gong, Quan', 'Goud, Aditya', 'Srinivasamaharaj, Srividya', 'Rajagopalan, Sanjay']",J Diabetes Res,,,True
293e8a49b5c0ee33d5e1098b3f4ca9b613c516fd,PMC,Homology-Independent Metrics for Comparative Genomics,http://dx.doi.org/10.1016/j.csbj.2015.04.005,PMC4446528,26029354,CC BY,"A mainstream procedure to analyze the wealth of genomic data available nowadays is the detection of homologous regions shared across genomes, followed by the extraction of biological information from the patterns of conservation and variation observed in such regions. Although of pivotal importance, comparative genomic procedures that rely on homology inference are obviously not applicable if no homologous regions are detectable. This fact excludes a considerable portion of “genomic dark matter” with no significant similarity — and, consequently, no inferred homology to any other known sequence — from several downstream comparative genomic methods. In this review we compile several sequence metrics that do not rely on homology inference and can be used to compare nucleotide sequences and extract biologically meaningful information from them. These metrics comprise several compositional parameters calculated from sequence data alone, such as GC content, dinucleotide odds ratio, and several codon bias metrics. They also share other interesting properties, such as pervasiveness (patterns persist on smaller scales) and phylogenetic signal. We also cite examples where these homology-independent metrics have been successfully applied to support several bioinformatics challenges, such as taxonomic classification of biological sequences without homology inference. They where also used to detect higher-order patterns of interactions in biological systems, ranging from detecting coevolutionary trends between the genomes of viruses and their hosts to characterization of gene pools of entire microbial communities. We argue that, if correctly understood and applied, homology-independent metrics can add important layers of biological information in comparative genomic studies without prior homology inference.",2015 May 4,"['Coutinho, Tarcisio José Domingos', 'Franco, Glória Regina', 'Lobo, Francisco Pereira']",Comput Struct Biotechnol J,,,False
9223fd6478822761845291fe2ac429ca6ddbb45a,PMC,Association of targeted multiplex PCR with resequencing microarray for the detection of multiple respiratory pathogens,http://dx.doi.org/10.3389/fmicb.2015.00532,PMC4446546,26074910,CC BY,"A large number of viral and bacterial organisms are responsible for community-acquired pneumonia (CAP) which contributes to substantial burden on health management. A new resequencing microarray (RPM-IVDC1) associated with targeted multiplex PCR was recently developed and validated for multiple respiratory viruses detection and discrimination. In this study, we evaluated the capability of RPM-IVDC1 for simultaneous identification of multiple viral and bacterial organisms. The nasopharyngeal aspirates (NPAs) of 110 consecutive CAP patients, aged from 1 month to 96 years old, were collected from five distinct general hospitals in Beijing during 1-year period. The samples were subjected to the RPM-IVDC1 established protocol as compared to a real-time PCR (qRT-PCR), which was used as standard. The results of virus detection were consistent with those previously described. A total of 37 of Streptococcus pneumoniae, 14 of Haemophilus influenzae, 10 of Mycoplasma pneumoniae, two of Klebsiella pneumoniae and one of Moraxella catarrhalis were detected by RPM-IVDC1. The sensitivities and specificities were compared with those of qRT-PCR for S. pneumoniae (100, 100%, respectively), H. influenzae (92.3, 97.9%, respectively), M. pneumoniae (69.2, 99.0%, respectively), K. pneumoniae (100, 100%, respectively), and M. catarrhalis (100, 100%, respectively). Additional 22 of Streptococcus spp., 24 of Haemophilus spp. and 16 of Neisseria spp. were identified. In addition, methicillin-resistant and carbapenemases allele were also found in nine of Staphylococcus spp. and one of K. pneumoniae, respectively. These results demonstrated the capability of RPM-IVDC1 for simultaneous detection of broad-spectrum respiratory pathogens in complex backgrounds and the advantage of accessing to the actual sequences, showing great potential use of epidemic outbreak investigation. The detection results should be carefully interpreted when introducing this technique in the clinical diagnostics.",2015 May 28,"['Shen, Hongwei', 'Zhu, Bingqing', 'Wang, Shulian', 'Mo, Haolian', 'Wang, Ji', 'Li, Jin', 'Zhang, Chen', 'Zeng, Huashu', 'Guan, Li', 'Shi, Weixian', 'Zhang, Yong', 'Ma, Xuejun']",Front Microbiol,,,True
bbe42ce008a9dd9e25c03c36113d763dba358cbb,PMC,Phosphatidic Acid Produced by Phospholipase D Promotes RNA Replication of a Plant RNA Virus,http://dx.doi.org/10.1371/journal.ppat.1004909,PMC4447390,26020241,CC BY,"Eukaryotic positive-strand RNA [(+)RNA] viruses are intracellular obligate parasites replicate using the membrane-bound replicase complexes that contain multiple viral and host components. To replicate, (+)RNA viruses exploit host resources and modify host metabolism and membrane organization. Phospholipase D (PLD) is a phosphatidylcholine- and phosphatidylethanolamine-hydrolyzing enzyme that catalyzes the production of phosphatidic acid (PA), a lipid second messenger that modulates diverse intracellular signaling in various organisms. PA is normally present in small amounts (less than 1% of total phospholipids), but rapidly and transiently accumulates in lipid bilayers in response to different environmental cues such as biotic and abiotic stresses in plants. However, the precise functions of PLD and PA remain unknown. Here, we report the roles of PLD and PA in genomic RNA replication of a plant (+)RNA virus, Red clover necrotic mosaic virus (RCNMV). We found that RCNMV RNA replication complexes formed in Nicotiana benthamiana contained PLDα and PLDβ. Gene-silencing and pharmacological inhibition approaches showed that PLDs and PLDs-derived PA are required for viral RNA replication. Consistent with this, exogenous application of PA enhanced viral RNA replication in plant cells and plant-derived cell-free extracts. We also found that a viral auxiliary replication protein bound to PA in vitro, and that the amount of PA increased in RCNMV-infected plant leaves. Together, our findings suggest that RCNMV hijacks host PA-producing enzymes to replicate.",2015 May 28,"['Hyodo, Kiwamu', 'Taniguchi, Takako', 'Manabe, Yuki', 'Kaido, Masanori', 'Mise, Kazuyuki', 'Sugawara, Tatsuya', 'Taniguchi, Hisaaki', 'Okuno, Tetsuro']",PLoS Pathog,,,True
1196301d4e04f2283f18f95fbbbd6bc5cf6e341f,PMC,The Use of Nanotrap Particles in the Enhanced Detection of Rift Valley Fever Virus Nucleoprotein,http://dx.doi.org/10.1371/journal.pone.0128215,PMC4447397,26020252,CC BY,"BACKGROUND: Rift Valley fever virus (RVFV) is a highly pathogenic arthropod-borne virus that has a detrimental effect on both livestock and human populations. While there are several diagnostic methodologies available for RVFV detection, many are not sensitive enough to diagnose early infections. Furthermore, detection may be hindered by high abundant proteins such as albumin. Previous findings have shown that Nanotrap particles can be used to significantly enhance detection of various small analytes of low abundance. We have expanded upon this repertoire to show that this simple and efficient sample preparation technology can drastically improve the detection of the RVFV nucleoprotein (NP), the most abundant and widely used viral protein for RVFV diagnostics. RESULTS: After screening multiple Nanotrap particle architectures, we found that one particle, NT45, was optimal for RVFV NP capture, as demonstrated by western blotting. NT45 significantly enhanced detection of the NP at levels undetectable without the technology. Importantly, we demonstrated that Nanotrap particles are capable of concentrating NP in a number of matrices, including infected cell lysates, viral supernatants, and animal sera. Specifically, NT45 enhanced detection of NP at various viral titers, multiplicity of infections, and time points. Our most dramatic results were observed in spiked serum samples, where high abundance serum proteins hindered detection of NP without Nanotrap particles. Nanotrap particles allowed for sample cleanup and subsequent detection of RVFV NP. Finally, we demonstrated that incubation of our samples with Nanotrap particles protects the NP from degradation over extended periods of time (up to 120 hours) and at elevated temperatures (at 37ºC). CONCLUSION: This study demonstrates that Nanotrap particles are capable of drastically lowering the limit of detection for RVFV NP by capturing, concentrating, and preserving RVFV NP in clinically relevant matrices. These studies can be extended to a wide range of pathogens and their analytes of diagnostic interest.",2015 May 28,"['Shafagati, Nazly', 'Lundberg, Lindsay', 'Baer, Alan', 'Patanarut, Alexis', 'Fite, Katherine', 'Lepene, Benjamin', 'Kehn-Hall, Kylene']",PLoS One,,,True
6e25ab9800baa443a7f103bd9e4940cac7db05f6,PMC,Aspects of the Health Inspection Authority in the People’s Republic of China,http://dx.doi.org/10.1186/s12889-015-1832-0,PMC4449968,25989798,CC BY,"BACKGROUND: In China, there was a pressing need to establish a governmental agency to oversee the organizations that provide public health and medical services. The Chinese Health Inspection Authority (HIA), a relatively independent organization functioning at each administrative level (provincial, municipal, and county), was mandated to conduct 11 health inspection functions to maintain efficient public health and medical services. These functions include issuing health permit, conducting health supervision and inspection, health testing and evaluation, case investigation, complaint handling, managing public health crisis, monitoring and safeguarding public health at major public events, enforcing supervision and inspection compliance, public health education, information management, and team training and management. Since the reform of the health inspection system by the Ministry of Health in 2000, the HIA underwent a series of changes and transitions. This study aimed to describe and assess the five factors that were considered to be important for meeting service delivery objectives of the HIA in the People’s Republic of China. METHODS: A total of 604 HIAs, sampled across three geographical regions of China at three administrative levels, participated in a cross-sectional survey conducted in 2013. Descriptive statistics were used to analyze the status of mandated operations, manpower, revenue and expenditures, and institutional infrastructure. Differences in these characteristics across the geographical regions and administrative levels were compared. RESULTS: On average, the HIAs had not fully implemented the 11 mandated functions at any administrative levels. Governmental financial allocations were the main sources of revenue. Three primary personnel employment models coexisted and most employed the quasi-civil service employment model. The institutional infrastructure did not meet governmental mandated standards with respect to building area or the number and types of equipment available to conduct key functions. CONCLUSIONS: In 2012, the majority of the HIAs in China at the provincial, municipal, and county levels did not meet the mandated requirements, although positive indications toward meeting these requirements were observed. It is necessary for the government to pay more attention to institutional resources (buildings, equipment, and the level of the staff’s educational attainment) and ensure that the HIAs can meet their service delivery objectives.",2015 May 20,"['Ma, Sha', 'Chen, Gang', 'Tan, B-K']",BMC Public Health,,,True
c5c188fe8bbf7f71f4f6f96dc52747deac68ee3f,PMC,The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes,http://dx.doi.org/10.1038/srep10942,PMC4450576,26028236,CC BY,"The novel avian origin influenza A (H7N9) virus has caused severe diseases in humans in eastern China since the spring of 2013. Fatal outcomes of H7N9 infections are often attributed to the severe pneumonia and acute respiratory distress syndrome (ARDS). There is urgent need to discover biomarkers predicting the progression of disease and fatal outcome of potentially lethal flu infections, based on sound statistical analysis. We discovered that 34 of the 48 cytokines and chemokines examined in this study were significantly elevated in the plasma samples from patients infected with H7N9. We report for the first time that the levels of MIF, SCF, MCP-1, HGF, and SCGF-β are highly positively linked to disease severity and the profile of mediators MIF, SCF, MCP-1, HGF, SCGF-β, IP-10, IL-18, and IFN-γ is an independent outcome predictor.",2015 Jun 1,"['Guo, Jing', 'Huang, Fengming', 'Liu, Jun', 'Chen, Yu', 'Wang, Wei', 'Cao, Bin', 'Zou, Zhen', 'Liu, Song', 'Pan, Jingcao', 'Bao, Changjun', 'Zeng, Mei', 'Xiao, Haixia', 'Gao, Hainv', 'Yang, Shigui', 'Zhao, Yan', 'Liu, Qiang', 'Zhou, Huandi', 'Zhu, Jingdong', 'Liu, Xiaoli', 'Liang, Weifeng', 'Yang, Yida', 'Zheng, Shufa', 'Yang, Jiezuan', 'Diao, Hongyan', 'Su, Kunkai', 'Shao, Li', 'Cao, Hongcui', 'Wu, Ying', 'Zhao, Min', 'Tan, Shuguang', 'Li, Hui', 'Xu, Xiaoqing', 'Wang, Chunmei', 'Zhang, Jianmin', 'Wang, Li', 'Wang, Jianwei', 'Xu, Jun', 'Li, Dangsheng', 'Zhong, Nanshan', 'Cao, Xuetao', 'Gao, George F.', 'Li, Lanjuan', 'Jiang, Chengyu']",Sci Rep,,,True
f72f1b06430dd304beddfb96b80d4a20aa8f3d23,PMC,The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes,http://dx.doi.org/10.1038/srep10942,PMC4450576,26028236,CC BY,"The novel avian origin influenza A (H7N9) virus has caused severe diseases in humans in eastern China since the spring of 2013. Fatal outcomes of H7N9 infections are often attributed to the severe pneumonia and acute respiratory distress syndrome (ARDS). There is urgent need to discover biomarkers predicting the progression of disease and fatal outcome of potentially lethal flu infections, based on sound statistical analysis. We discovered that 34 of the 48 cytokines and chemokines examined in this study were significantly elevated in the plasma samples from patients infected with H7N9. We report for the first time that the levels of MIF, SCF, MCP-1, HGF, and SCGF-β are highly positively linked to disease severity and the profile of mediators MIF, SCF, MCP-1, HGF, SCGF-β, IP-10, IL-18, and IFN-γ is an independent outcome predictor.",2015 Jun 1,"['Guo, Jing', 'Huang, Fengming', 'Liu, Jun', 'Chen, Yu', 'Wang, Wei', 'Cao, Bin', 'Zou, Zhen', 'Liu, Song', 'Pan, Jingcao', 'Bao, Changjun', 'Zeng, Mei', 'Xiao, Haixia', 'Gao, Hainv', 'Yang, Shigui', 'Zhao, Yan', 'Liu, Qiang', 'Zhou, Huandi', 'Zhu, Jingdong', 'Liu, Xiaoli', 'Liang, Weifeng', 'Yang, Yida', 'Zheng, Shufa', 'Yang, Jiezuan', 'Diao, Hongyan', 'Su, Kunkai', 'Shao, Li', 'Cao, Hongcui', 'Wu, Ying', 'Zhao, Min', 'Tan, Shuguang', 'Li, Hui', 'Xu, Xiaoqing', 'Wang, Chunmei', 'Zhang, Jianmin', 'Wang, Li', 'Wang, Jianwei', 'Xu, Jun', 'Li, Dangsheng', 'Zhong, Nanshan', 'Cao, Xuetao', 'Gao, George F.', 'Li, Lanjuan', 'Jiang, Chengyu']",Sci Rep,,,False
7458d605a0f34ffeeb3a2073c654f462ed1716e1,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.15.010615,PMC4450712,,CC BY,,2015 Jun 1,,Bull World Health Organ,,,False
135a7409bb3edb0dab450d94baa025e28fdaa586,PMC,Global funding for local health issues,http://dx.doi.org/10.2471/BLT.15.030615,PMC4450714,26240457,CC BY,Jeremy Farrar tells Fiona Fleck why global health research must go local to respond to social needs.,2015 Jun 1,,Bull World Health Organ,,,False
e546530d3c2507a91afb8ed59c87cac0c8b501da,PMC,Nucleocytoplasmic transport of nucleocapsid proteins of enveloped RNA viruses,http://dx.doi.org/10.3389/fmicb.2015.00553,PMC4451415,26082769,CC BY,"Most viruses with non-segmented single stranded RNA genomes complete their life cycle in the cytoplasm of infected cells. However, despite undergoing replication in the cytoplasm, the structural proteins of some of these RNA viruses localize to the nucleus at specific times in the virus life cycle, primarily early in infection. Limited evidence suggests that this enhances successful viral replication by interfering with or inhibiting the host antiviral response. Nucleocapsid proteins of RNA viruses have a well-established, essential cytoplasmic role in virus replication and assembly. Intriguingly, nucleocapsid proteins of some RNA viruses also localize to the nucleus/nucleolus of infected cells. Their nuclear function is less well understood although significant advances have been made in recent years. This review will focus on the nucleocapsid protein of cytoplasmic enveloped RNA viruses, including their localization to the nucleus/nucleolus and function therein. A greater understanding of the nuclear localization of nucleocapsid proteins has the potential to enhance therapeutic strategies as it can be a target for the development of live-attenuated vaccines or antiviral drugs.",2015 Jun 2,"['Wulan, Wahyu N.', 'Heydet, Deborah', 'Walker, Erin J.', 'Gahan, Michelle E.', 'Ghildyal, Reena']",Front Microbiol,,,True
2b244041ab6f2ab167b76c5b17332c5598b56431,PMC,Computational Docking Study of p7 Ion Channel from HCV Genotype 3 and Genotype 4 and Its Interaction with Natural Compounds,http://dx.doi.org/10.1371/journal.pone.0126510,PMC4451521,26030803,CC BY,"BACKGROUND: The current standard care therapy for hepatitis C virus (HCV) infection consists of two regimes, namely interferon-based and interferon-free treatments. The treatment through the combination of ribavirin and pegylated interferon is expensive, only mildly effective, and is associated with severe side effects. In 2011, two direct-acting antiviral (DAA) drugs, boceprevir and telaprevir, were licensed that have shown enhanced sustained virologic response (SVR) in phase III clinical trial, however, these interferon-free treatments are more sensitive to HCV genotype 1 infection. The variable nature of HCV, and the limited number of inhibitors developed thus aim in expanding the repertoire of available drug targets, resulting in targeting the virus assembly therapeutically. AIM: We conducted this study to predict the 3D structure of the p7 protein from the HCV genotypes 3 and 4. Approximately 63 amino acid residues encoded in HCV render this channel sensitive to inhibitors, making p7 a promising target for novel therapies. HCV p7 protein forms a small membrane known as viroporin, and is essential for effective self-assembly of large channels that conduct cation assembly and discharge infectious virion particles. METHOD: In this study, we screened drugs and flavonoids known to disrupt translation and production of HCV proteins, targeted against the active site of p7 residues of HCV genotype 3 (GT3) (isolatek3a) and HCV genotype 4a (GT4) (isolateED43). Furthermore, we conducted a quantitative structure–activity relationship and docking interaction study. RESULTS: The drug NB-DNJ formed the highest number of hydrogen bond interactions with both modeled p7 proteins with high interaction energy, followed by BIT225. A flavonoid screen demonstrated that Epigallocatechin gallate (EGCG), nobiletin, and quercetin, have more binding modes in GT3 than in GT4. Thus, the predicted p7 protein molecule of HCV from GT3 and GT4 provides a general avenue to target structure-based antiviral compounds. CONCLUSIONS: We hypothesize that the inhibitors of viral p7 identified in this screen may be a new class of potent agents, but further confirmation in vitro and in vivo is essential. This structure-guided drug design for both GT3 and GT4 can lead to the identification of drug-like natural compounds, confirming p7 as a new target in the rapidly increasing era of HCV.",2015 Jun 1,"['Mathew, Shilu', 'Fatima, Kaneez', 'Fatmi, M. Qaiser', 'Archunan, Govindaraju', 'Ilyas, Muhammad', 'Begum, Nargis', 'Azhar, Esam', 'Damanhouri, Ghazi', 'Qadri, Ishtiaq']",PLoS One,,,True
0b7d50ddfae18226d4a66c578d9235d872c85056,PMC,T(FH) cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1,http://dx.doi.org/10.1038/srep10443,PMC4451806,26034905,CC BY,"CD4(+) T follicular helper cells (T(FH)) in germinal centers are required for maturation of B-cells. While the role of T(FH)-cells has been studied in blood and lymph nodes of HIV-1 infected individuals, its role in the mucosal tissues has not been investigated. We show that the gut and female reproductive tract (FRT) of humanized DRAG mice have a high level of human lymphocytes and a high frequency of T(FH) (CXCR5(+)PD-1(++)) and precursor-T(FH) (CXCR5(+)PD-1(+)) cells. The majority of T(FH)-cells expressed CCR5 and CXCR3 and are the most permissive to HIV-1 infection. A single low-dose intravaginal HIV-1 challenge of humanized DRAG mice results in 100% infectivity with accumulation of T(FH)-cells mainly in the Peyer’s patches and FRT. The novel finding of T(FH)-cells in the FRT may contribute to the high susceptibility of DRAG mice to HIV-1 infection. This mouse model thus provides new opportunities to study T(FH)-cells and to evaluate HIV-1 vaccines.",2015 Jun 2,"['Allam, Atef', 'Majji, Sai', 'Peachman, Kristina', 'Jagodzinski, Linda', 'Kim, Jiae', 'Ratto-Kim, Silvia', 'Wijayalath, Wathsala', 'Merbah, Melanie', 'Kim, Jerome H.', 'Michael, Nelson L.', 'Alving, Carl R.', 'Casares, Sofia', 'Rao, Mangala']",Sci Rep,,,True
1ae6649a17c7eb7f14611bbabcf0cb0a60121d7c,PMC,T(FH) cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1,http://dx.doi.org/10.1038/srep10443,PMC4451806,26034905,CC BY,"CD4(+) T follicular helper cells (T(FH)) in germinal centers are required for maturation of B-cells. While the role of T(FH)-cells has been studied in blood and lymph nodes of HIV-1 infected individuals, its role in the mucosal tissues has not been investigated. We show that the gut and female reproductive tract (FRT) of humanized DRAG mice have a high level of human lymphocytes and a high frequency of T(FH) (CXCR5(+)PD-1(++)) and precursor-T(FH) (CXCR5(+)PD-1(+)) cells. The majority of T(FH)-cells expressed CCR5 and CXCR3 and are the most permissive to HIV-1 infection. A single low-dose intravaginal HIV-1 challenge of humanized DRAG mice results in 100% infectivity with accumulation of T(FH)-cells mainly in the Peyer’s patches and FRT. The novel finding of T(FH)-cells in the FRT may contribute to the high susceptibility of DRAG mice to HIV-1 infection. This mouse model thus provides new opportunities to study T(FH)-cells and to evaluate HIV-1 vaccines.",2015 Jun 2,"['Allam, Atef', 'Majji, Sai', 'Peachman, Kristina', 'Jagodzinski, Linda', 'Kim, Jiae', 'Ratto-Kim, Silvia', 'Wijayalath, Wathsala', 'Merbah, Melanie', 'Kim, Jerome H.', 'Michael, Nelson L.', 'Alving, Carl R.', 'Casares, Sofia', 'Rao, Mangala']",Sci Rep,,,False
7870870602f0a4edb3a7ea468659e2eb23cb2202,PMC,Protection against Amoebic Liver Abscess in Hamster by Intramuscular Immunization with an Autographa californica Baculovirus Driving the Expression of the Gal-Lectin LC3 Fragment,http://dx.doi.org/10.1155/2015/760598,PMC4452260,26090442,CC BY,"In a previous study, we demonstrated that oral immunization using Autographa californica baculovirus driving the expression of the Gal-lectin LC3 fragment (AcNPV-LC3) of Entamoeba histolytica conferred protection against ALA development in hamsters. In this study, we determined the ability of AcNPV-LC3 to protect against ALA by the intramuscular route as well as the liver immune response associated with protection. Results showed that 55% of hamsters IM immunized with AcNPV-LC3 showed sterile protection against ALA, whereas other 20% showed reduction in the size and extent of abscesses, resulting in some protection in 75% of animals compared to the sham control group. Levels of protection showed a linear correlation with the development and intensity of specific antiamoeba cellular and humoral responses, evaluated in serum and spleen of hamsters, respectively. Evaluation of the Th1/Th2 cytokine patterns expressed in the liver of hamsters showed that sterile protection was associated with the production of high levels of IFNγ and IL-4. These results suggest that the baculovirus system is equally efficient by the intramuscular as well as the oral routes for ALA protection and that the Gal-lectin LC3 fragment is a highly protective antigen against hepatic amoebiasis through the local induction of IFNγ and IL-4.",2015 May 19,"['Meneses-Ruiz, Dulce María', 'Aguilar-Diaz, Hugo', 'Bobes, Raúl José', 'Sampieri, Alicia', 'Vaca, Luis', 'Laclette, Juan Pedro', 'Carrero, Julio César']",Biomed Res Int,,,True
252e6f853b7025fa235432baf9869ae4f51a020d,PMC,Host Tissue and Glycan Binding Specificities of Avian Viral Attachment Proteins Using Novel Avian Tissue Microarrays,http://dx.doi.org/10.1371/journal.pone.0128893,PMC4452732,26035584,CC BY,"The initial interaction between viral attachment proteins and the host cell is a critical determinant for the susceptibility of a host for a particular virus. To increase our understanding of avian pathogens and the susceptibility of poultry species, we developed novel avian tissue microarrays (TMAs). Tissue binding profiles of avian viral attachment proteins were studied by performing histochemistry on multi-species TMA, comprising of selected tissues from ten avian species, and single-species TMAs, grouping organ systems of each species together. The attachment pattern of the hemagglutinin protein was in line with the reported tropism of influenza virus H5N1, confirming the validity of TMAs in profiling the initial virus-host interaction. The previously believed chicken-specific coronavirus (CoV) M41 spike (S1) protein displayed a broad attachment pattern to respiratory tissues of various avian species, albeit with lower affinity than hemagglutinin, suggesting that other avian species might be susceptible for chicken CoV. When comparing tissue-specific binding patterns of various avian coronaviral S1 proteins on the single-species TMAs, chicken and partridge CoV S1 had predominant affinity for the trachea, while pigeon CoV S1 showed marked preference for lung of their respective hosts. Binding of all coronaviral S1 proteins was dependent on sialic acids; however, while chicken CoV S1 preferred sialic acids type I lactosamine (Gal(1-3)GlcNAc) over type II (Gal(1-4)GlcNAc), the fine glycan specificities of pigeon and partridge CoVs were different, as chicken CoV S1-specific sialylglycopolymers could not block their binding to tissues. Taken together, TMAs provide a novel platform in the field of infectious diseases to allow identification of binding specificities of viral attachment proteins and are helpful to gain insight into the susceptibility of host and organ for avian pathogens.",2015 Jun 2,"['Ambepitiya Wickramasinghe, Iresha N.', 'de Vries, Robert P.', 'Eggert, Amber M.', 'Wandee, Nantaporn', 'de Haan, Cornelis A. M.', 'Gröne, Andrea', 'Verheije, Monique H.']",PLoS One,,,True
118373b29085c6212547a34993be16eb98008dd0,PMC,Host Tissue and Glycan Binding Specificities of Avian Viral Attachment Proteins Using Novel Avian Tissue Microarrays,http://dx.doi.org/10.1371/journal.pone.0128893,PMC4452732,26035584,CC BY,"The initial interaction between viral attachment proteins and the host cell is a critical determinant for the susceptibility of a host for a particular virus. To increase our understanding of avian pathogens and the susceptibility of poultry species, we developed novel avian tissue microarrays (TMAs). Tissue binding profiles of avian viral attachment proteins were studied by performing histochemistry on multi-species TMA, comprising of selected tissues from ten avian species, and single-species TMAs, grouping organ systems of each species together. The attachment pattern of the hemagglutinin protein was in line with the reported tropism of influenza virus H5N1, confirming the validity of TMAs in profiling the initial virus-host interaction. The previously believed chicken-specific coronavirus (CoV) M41 spike (S1) protein displayed a broad attachment pattern to respiratory tissues of various avian species, albeit with lower affinity than hemagglutinin, suggesting that other avian species might be susceptible for chicken CoV. When comparing tissue-specific binding patterns of various avian coronaviral S1 proteins on the single-species TMAs, chicken and partridge CoV S1 had predominant affinity for the trachea, while pigeon CoV S1 showed marked preference for lung of their respective hosts. Binding of all coronaviral S1 proteins was dependent on sialic acids; however, while chicken CoV S1 preferred sialic acids type I lactosamine (Gal(1-3)GlcNAc) over type II (Gal(1-4)GlcNAc), the fine glycan specificities of pigeon and partridge CoVs were different, as chicken CoV S1-specific sialylglycopolymers could not block their binding to tissues. Taken together, TMAs provide a novel platform in the field of infectious diseases to allow identification of binding specificities of viral attachment proteins and are helpful to gain insight into the susceptibility of host and organ for avian pathogens.",2015 Jun 2,"['Ambepitiya Wickramasinghe, Iresha N.', 'de Vries, Robert P.', 'Eggert, Amber M.', 'Wandee, Nantaporn', 'de Haan, Cornelis A. M.', 'Gröne, Andrea', 'Verheije, Monique H.']",PLoS One,,,True
dd4a3353ae21a249a81f30e23fc416a1d948887b,PMC,Interaction between the Natural Components in Danhong Injection (DHI) with Serum Albumin (SA) and the Influence of the Coexisting Multi-Components on the SaB-BSA Binding System: Fluorescence and Molecular Docking Studies,http://dx.doi.org/10.1371/journal.pone.0128919,PMC4452768,26035712,CC BY,"Danhong injection (DHI) is a widely used Chinese Materia Medica standardized product for the clinical treatment of ischemic encephalopathy and coronary heart disease. The bindings of eight natural components in DHI between bovine serum albumin (BSA) were studied by fluorescence spectroscopy technology and molecular docking. According to the results, the quenching process of salvianolic acid B and hydroxysafflor yellow A was a static quenching procedure through the analysis of quenching data by the Stern-Volmer equation, the modified Stern-Volmer equation, and the modified Scatchard equation. Meanwhile, syringin (Syr) enhanced the fluorescence of BSA, and the data were analyzed using the Lineweaver-Burk equation. Molecular docking suggested that all of these natural components bind to serum albumin at the site I location. Further competitive experiments of SaB confirmed the result of molecular docking studies duo to the displacement of warfarin by SaB. Base on these studies, we selected SaB as a research target because it presented the strongest binding ability to BSA and investigated the influence of the multi-components coexisting in DHI on the interaction between the components of the SaB-BSA binding system. The participation of these natural components in DHI affected the interaction between the components of the SaB-BSA system. Therefore, when DHI is used in mammals, SaB is released from serum albumin more quickly than it is used alone. This work would provide a new experiment basis for revealing the scientific principle of compatibility for Traditional Chinese Medicine.",2015 Jun 2,"['Hao, Jia', 'Zhang, Yingyue', 'Wang, Xingrui', 'Yan, Huo', 'Liu, Erwei', 'Gao, Xiumei']",PLoS One,,,True
11f8eeb589bf8737b2805b3bb50ca12b73884c64,PMC,Identification of Putative ORF5 Protein of Porcine Circovirus Type 2 and Functional Analysis of GFP-Fused ORF5 Protein,http://dx.doi.org/10.1371/journal.pone.0127859,PMC4452787,26035722,CC BY,"Porcine circovirus type 2 (PCV2) is the essential infectious agent responsible for causing porcine circovirus-associated diseases in pigs. To date, eleven RNAs and five viral proteins of PCV2 have been detected. Here, we identified a novel viral gene within the PCV2 genome, termed ORF5, that exists at both the transcriptional and translational level during productive infection of PCV2 in porcine alveolar macrophages 3D4/2 (PAMs). Northern blot analysis was used to demonstrate that the ORF5 gene measures 180 bp in length and overlaps completely with ORF1 when read in the same direction. Site-directed mutagenesis was used to show that the ORF5 protein is not essential for PCV2 replication. To investigate the biological functions of the novel protein, we constructed a recombinant eukaryotic expression plasmid capable of expressing PCV2 ORF5. The results show that the GFP-tagged PCV2 ORF5 protein localizes to the endoplasmic reticulum (ER), is degraded via the proteasome, inhibits PAM growth and prolongs the S-phase of the cell cycle. Further studies show that the GFP-tagged PCV2 ORF5 protein induces ER stress and activates NF-κB, which was further confirmed by a significant upregulation in IL-6, IL-8 and COX-2 expression. In addition, five cellular proteins (GPNMB, CYP1A1, YWHAB, ZNF511 and SRSF3) were found to interact with ORF5 via yeast two-hybrid assay. These findings provide novel information on the identification and functional analysis of the PCV2 ORF5 protein and are likely to be of benefit in elucidating the molecular mechanisms of PCV2 pathogenicity. However, additional experiments are needed to validate the expression and function of the ORF5 protein during PCV2 infection in vitro before any definitive conclusion can be drawn.",2015 Jun 2,"['Lv, Qizhuang', 'Guo, Kangkang', 'Xu, Han', 'Wang, Tao', 'Zhang, Yanming']",PLoS One,,,True
616eb9a60a8da572b0a60b6d33f4618c91c7b55c,PMC,Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s) Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes,http://dx.doi.org/10.3390/v7052358,PMC4452910,26008694,CC BY,"Human coronavirus OC43 (HCoV-OC43) is one of five currently circulating human coronaviruses responsible for respiratory infections. Like all coronaviruses, it is characterized by its genome’s high plasticity. The objectives of the current study were to detect genetically distinct genotypes and eventually recombinant genotypes in samples collected in Lower Normandy between 2001 and 2013. To this end, we sequenced complete nsp12, S, and N genes of 15 molecular isolates of HCoV-OC43 from clinical samples and compared them to available data from the USA, Belgium, and Hong-Kong. A new cluster E was invariably detected from nsp12, S, and N data while the analysis of nsp12 and N genes revealed the existence of new F and G clusters respectively. The association of these different clusters of genes in our specimens led to the description of thirteen genetically distinct genotypes, among which eight recombinant viruses were discovered. Identification of these recombinant viruses, together with temporal analysis and tMRCA estimation, provides important information for understanding the dynamics of the evolution of these epidemic coronaviruses.",2015 May 7,"['Kin, Nathalie', 'Miszczak, Fabien', 'Lin, Wei', 'Ar Gouilh, Meriadeg', 'Vabret, Astrid', None]",Viruses,,,True
bb11206963e831f1652775d26e3e5e48634a4545,PMC,The Use of Convalescent Sera in Immune-Electron Microscopy to Detect Non-Suspected/New Viral Agents,http://dx.doi.org/10.3390/v7052683,PMC4452926,26008707,CC BY,"Negative staining electron microscopy methods can be employed for the diagnosis of viral particles in animal samples. In fact, negative staining electron microscopy methods are used to identify viruses, especially in minor species and wild animals, when no other methods are available and in cases of rare, emerging or re-emerging infections. In particular, immune-electron-microscopy with convalescent sera is employed to detect etiological agents when there are undiagnosed clinical outbreaks, when alternative diagnostic methods fail due to the lack of immunological reagents and primers, and when there is no indicative clinical suspect. An overview of immune-electron-microscopy with convalescent sera’s use in the diagnosis of new and unsuspected viruses in animals of domestic and wild species is provided through the descriptions of the following four diagnostic veterinary cases: (I) enteric viruses of pigs: Porcine Rotavirus, Porcine Epidemic Diarrhea Virus, Porcine Circovirus and Porcine Torovirus; (II) Rotavirus and astrovirus in young turkeys with enteritis; (III) Parvovirus-like particles in pheasants; and (IV) Lagoviruses: Rabbit Hemorrhagic Disease Virus and European Brown Hare Syndrome Virus.",2015 May 22,"['Lavazza, Antonio', 'Tittarelli, Cristiana', 'Cerioli, Monica']",Viruses,,,True
57f687e997bc7338adaefa13542e1f9ae7ddd7e6,PMC,Responding to the Pandemic of Falsified Medicines,http://dx.doi.org/10.4269/ajtmh.14-0393,PMC4455086,25897060,CC BY,"Over the past decade, the number of countries reporting falsified (fake, spurious/falsely labeled/counterfeit) medicines and the types and quantities of fraudulent drugs being distributed have increased greatly. The obstacles in combating falsified pharmaceuticals include 1) lack of consensus on definitions, 2) paucity of reliable and scalable technology to detect fakes before they reach patients, 3) poor global and national leadership and accountability systems for combating this scourge, and 4) deficient manufacturing and regulatory challenges, especially in China and India where fake products often originate. The major needs to improve the quality of the world's medicines fall into three main areas: 1) research to develop and compare accurate and affordable tools to identify high-quality drugs at all levels of distribution; 2) an international convention and national legislation to facilitate production and utilization of high-quality drugs and protect all countries from the criminal and the negligent who make, distribute, and sell life-threatening products; and 3) a highly qualified, well-supported international science and public health organization that will establish standards, drug-quality surveillance, and training programs like the U.S. Food and Drug Administration. Such leadership would give authoritative guidance for countries in cooperation with national medical regulatory agencies, pharmaceutical companies, and international agencies, all of which have an urgent interest and investment in ensuring that patients throughout the world have access to good quality medicines. The organization would also advocate strongly for including targets for achieving good quality medicines in the United Nations Millennium Development Goals and Sustainable Development Goals.",2015 Jun 3,"['Nayyar, Gaurvika M. L.', 'Attaran, Amir', 'Clark, John P.', 'Culzoni, M. Julia', 'Fernandez, Facundo M.', 'Herrington, James E.', 'Kendall, Megan', 'Newton, Paul N.', 'Breman, Joel G.']",Am J Trop Med Hyg,,,True
fc5e4a2de7d202adad95ea3fe26625bdebe817cf,PMC,Facilitated Tau Degradation by USP14 Aptamers via Enhanced Proteasome Activity,http://dx.doi.org/10.1038/srep10757,PMC4455164,26041011,CC BY,"The ubiquitin-proteasome system (UPS) is the primary mechanism by which intracellular proteins, transcription factors, and many proteotoxic proteins with aggregation-prone structures are degraded. The UPS is reportedly downregulated in various neurodegenerative disorders, with increased proteasome activity shown to be beneficial in many related disease models. Proteasomes function under tonic inhibitory conditions, possibly via the ubiquitin chain-trimming function of USP14, a proteasome-associated deubiquitinating enzyme (DUB). We identified three specific RNA aptamers of USP14 (USP14-1, USP14-2, and USP14-3) that inhibited its deubiquitinating activity. The nucleotide sequences of these non-cytotoxic USP14 aptamers contained conserved GGAGG motifs, with G-rich regions upstream, and similar secondary structures. They efficiently elevated proteasomal activity, as determined by the increased degradation of small fluorogenic peptide substrates and physiological polyubiquitinated Sic1 proteins. Additionally, proteasomal degradation of tau proteins was facilitated in the presence of the UPS14 aptamers in vitro. Our results indicate that these novel inhibitory UPS14 aptamers can be used to enhance proteasome activity, and to facilitate the degradation of proteotoxic proteins, thereby protecting cells from various neurodegenerative stressors.",2015 Jun 4,"['Lee, Jung Hoon', 'Shin, Seung Kyun', 'Jiang, Yanxialei', 'Choi, Won Hoon', 'Hong, Chaesun', 'Kim, Dong-Eun', 'Lee, Min Jae']",Sci Rep,,,True
d77a804e5bfdfe18f1f70345b2931ab2cb7eec17,PMC,Facilitated Tau Degradation by USP14 Aptamers via Enhanced Proteasome Activity,http://dx.doi.org/10.1038/srep10757,PMC4455164,26041011,CC BY,"The ubiquitin-proteasome system (UPS) is the primary mechanism by which intracellular proteins, transcription factors, and many proteotoxic proteins with aggregation-prone structures are degraded. The UPS is reportedly downregulated in various neurodegenerative disorders, with increased proteasome activity shown to be beneficial in many related disease models. Proteasomes function under tonic inhibitory conditions, possibly via the ubiquitin chain-trimming function of USP14, a proteasome-associated deubiquitinating enzyme (DUB). We identified three specific RNA aptamers of USP14 (USP14-1, USP14-2, and USP14-3) that inhibited its deubiquitinating activity. The nucleotide sequences of these non-cytotoxic USP14 aptamers contained conserved GGAGG motifs, with G-rich regions upstream, and similar secondary structures. They efficiently elevated proteasomal activity, as determined by the increased degradation of small fluorogenic peptide substrates and physiological polyubiquitinated Sic1 proteins. Additionally, proteasomal degradation of tau proteins was facilitated in the presence of the UPS14 aptamers in vitro. Our results indicate that these novel inhibitory UPS14 aptamers can be used to enhance proteasome activity, and to facilitate the degradation of proteotoxic proteins, thereby protecting cells from various neurodegenerative stressors.",2015 Jun 4,"['Lee, Jung Hoon', 'Shin, Seung Kyun', 'Jiang, Yanxialei', 'Choi, Won Hoon', 'Hong, Chaesun', 'Kim, Dong-Eun', 'Lee, Min Jae']",Sci Rep,,,False
05916d82efe1f937ee48f09df4e5d7c6fede83d3,PMC,Pattern formation in multiplex networks,http://dx.doi.org/10.1038/srep10840,PMC4455352,26042606,CC BY,"The advances in understanding complex networks have generated increasing interest in dynamical processes occurring on them. Pattern formation in activator-inhibitor systems has been studied in networks, revealing differences from the classical continuous media. Here we study pattern formation in a new framework, namely multiplex networks. These are systems where activator and inhibitor species occupy separate nodes in different layers. Species react across layers but diffuse only within their own layer of distinct network topology. This multiplicity generates heterogeneous patterns with significant differences from those observed in single-layer networks. Remarkably, diffusion-induced instability can occur even if the two species have the same mobility rates; condition which can never destabilize single-layer networks. The instability condition is revealed using perturbation theory and expressed by a combination of degrees in the different layers. Our theory demonstrates that the existence of such topology-driven instabilities is generic in multiplex networks, providing a new mechanism of pattern formation.",2015 Jun 4,"['Kouvaris, Nikos E.', 'Hata, Shigefumi', 'Guilera, Albert Díaz-']",Sci Rep,,,True
60c4a22f7179cf74c681f6aca2c2bff78ba4f8bb,PMC,Pattern formation in multiplex networks,http://dx.doi.org/10.1038/srep10840,PMC4455352,26042606,CC BY,"The advances in understanding complex networks have generated increasing interest in dynamical processes occurring on them. Pattern formation in activator-inhibitor systems has been studied in networks, revealing differences from the classical continuous media. Here we study pattern formation in a new framework, namely multiplex networks. These are systems where activator and inhibitor species occupy separate nodes in different layers. Species react across layers but diffuse only within their own layer of distinct network topology. This multiplicity generates heterogeneous patterns with significant differences from those observed in single-layer networks. Remarkably, diffusion-induced instability can occur even if the two species have the same mobility rates; condition which can never destabilize single-layer networks. The instability condition is revealed using perturbation theory and expressed by a combination of degrees in the different layers. Our theory demonstrates that the existence of such topology-driven instabilities is generic in multiplex networks, providing a new mechanism of pattern formation.",2015 Jun 4,"['Kouvaris, Nikos E.', 'Hata, Shigefumi', 'Guilera, Albert Díaz-']",Sci Rep,,,False
207bf71776ac6427c03a4dffa991148bb6dd4833,PMC,Epidemic predictions in an imperfect world: modelling disease spread with partial data,http://dx.doi.org/10.1098/rspb.2015.0205,PMC4455802,25948687,CC BY,"‘Big-data’ epidemic models are being increasingly used to influence government policy to help with control and eradication of infectious diseases. In the case of livestock, detailed movement records have been used to parametrize realistic transmission models. While livestock movement data are readily available in the UK and other countries in the EU, in many countries around the world, such detailed data are not available. By using a comprehensive database of the UK cattle trade network, we implement various sampling strategies to determine the quantity of network data required to give accurate epidemiological predictions. It is found that by targeting nodes with the highest number of movements, accurate predictions on the size and spatial spread of epidemics can be made. This work has implications for countries such as the USA, where access to data is limited, and developing countries that may lack the resources to collect a full dataset on livestock movements.",2015 Jun 7,"['Dawson, Peter M.', 'Werkman, Marleen', 'Brooks-Pollock, Ellen', 'Tildesley, Michael J.']",Proc Biol Sci,,,True
63a48c7eba8cc3c450016ba75dd52baf62ab0196,PMC,Epidemic predictions in an imperfect world: modelling disease spread with partial data,http://dx.doi.org/10.1098/rspb.2015.0205,PMC4455802,25948687,CC BY,"‘Big-data’ epidemic models are being increasingly used to influence government policy to help with control and eradication of infectious diseases. In the case of livestock, detailed movement records have been used to parametrize realistic transmission models. While livestock movement data are readily available in the UK and other countries in the EU, in many countries around the world, such detailed data are not available. By using a comprehensive database of the UK cattle trade network, we implement various sampling strategies to determine the quantity of network data required to give accurate epidemiological predictions. It is found that by targeting nodes with the highest number of movements, accurate predictions on the size and spatial spread of epidemics can be made. This work has implications for countries such as the USA, where access to data is limited, and developing countries that may lack the resources to collect a full dataset on livestock movements.",2015 Jun 7,"['Dawson, Peter M.', 'Werkman, Marleen', 'Brooks-Pollock, Ellen', 'Tildesley, Michael J.']",Proc Biol Sci,,,False
afd95cb874e0f82bbbdd467f64eaddd8fc904f86,PMC,Epidemic predictions in an imperfect world: modelling disease spread with partial data,http://dx.doi.org/10.1098/rspb.2015.0205,PMC4455802,25948687,CC BY,"‘Big-data’ epidemic models are being increasingly used to influence government policy to help with control and eradication of infectious diseases. In the case of livestock, detailed movement records have been used to parametrize realistic transmission models. While livestock movement data are readily available in the UK and other countries in the EU, in many countries around the world, such detailed data are not available. By using a comprehensive database of the UK cattle trade network, we implement various sampling strategies to determine the quantity of network data required to give accurate epidemiological predictions. It is found that by targeting nodes with the highest number of movements, accurate predictions on the size and spatial spread of epidemics can be made. This work has implications for countries such as the USA, where access to data is limited, and developing countries that may lack the resources to collect a full dataset on livestock movements.",2015 Jun 7,"['Dawson, Peter M.', 'Werkman, Marleen', 'Brooks-Pollock, Ellen', 'Tildesley, Michael J.']",Proc Biol Sci,,,False
66a137256be1759200f9fc27164e526287470c8e,PMC,Epidemic predictions in an imperfect world: modelling disease spread with partial data,http://dx.doi.org/10.1098/rspb.2015.0205,PMC4455802,25948687,CC BY,"‘Big-data’ epidemic models are being increasingly used to influence government policy to help with control and eradication of infectious diseases. In the case of livestock, detailed movement records have been used to parametrize realistic transmission models. While livestock movement data are readily available in the UK and other countries in the EU, in many countries around the world, such detailed data are not available. By using a comprehensive database of the UK cattle trade network, we implement various sampling strategies to determine the quantity of network data required to give accurate epidemiological predictions. It is found that by targeting nodes with the highest number of movements, accurate predictions on the size and spatial spread of epidemics can be made. This work has implications for countries such as the USA, where access to data is limited, and developing countries that may lack the resources to collect a full dataset on livestock movements.",2015 Jun 7,"['Dawson, Peter M.', 'Werkman, Marleen', 'Brooks-Pollock, Ellen', 'Tildesley, Michael J.']",Proc Biol Sci,,,True
57a926dfc15144fb103d05fd16a3b2cd9982d348,PMC,Epidemic predictions in an imperfect world: modelling disease spread with partial data,http://dx.doi.org/10.1098/rspb.2015.0205,PMC4455802,25948687,CC BY,"‘Big-data’ epidemic models are being increasingly used to influence government policy to help with control and eradication of infectious diseases. In the case of livestock, detailed movement records have been used to parametrize realistic transmission models. While livestock movement data are readily available in the UK and other countries in the EU, in many countries around the world, such detailed data are not available. By using a comprehensive database of the UK cattle trade network, we implement various sampling strategies to determine the quantity of network data required to give accurate epidemiological predictions. It is found that by targeting nodes with the highest number of movements, accurate predictions on the size and spatial spread of epidemics can be made. This work has implications for countries such as the USA, where access to data is limited, and developing countries that may lack the resources to collect a full dataset on livestock movements.",2015 Jun 7,"['Dawson, Peter M.', 'Werkman, Marleen', 'Brooks-Pollock, Ellen', 'Tildesley, Michael J.']",Proc Biol Sci,,,False
ce43f8f05a5db366babc9a6bfa086219534de208,PMC,HIV infection and antiretroviral therapy lead to unfolded protein response activation,http://dx.doi.org/10.1186/s12985-015-0298-0,PMC4455982,25976933,CC BY,"BACKGROUND: The unfolded protein response (UPR) is one of the pathways triggered to ensure quality control of the proteins assembled in the endoplasmic reticulum (ER) when cell homeostasis is compromised. This mechanism is primarily composed of three transmembrane proteins serving as stress sensors: PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE1). These three proteins’ synergic action elicits translation and transcriptional downstream pathways, leading to less protein production and activating genes that encode important proteins in folding processes, including chaperones. Previous reports showed that viruses have evolved mechanisms to curtail or customize this UPR signaling for their own benefit. However, HIV infection’s effect on the UPR has scarcely been investigated. METHODS: This work investigated UPR modulation by HIV infection by assessing UPR-related protein expression under in vitro and in vivo conditions via Western blotting. Antiretroviral (ARV) drugs’ influence on this stress response was also considered. RESULTS: In in vitro and in vivo analyses, our results confirm that HIV infection activates stress-response components and that ARV therapy contributes to changes in the UPR’s activation profile. CONCLUSIONS: This is the first report showing UPR-related protein expression in HIV target cells derived directly from HIV-infected patients receiving different ARV therapies. Thus, two mechanisms may occur simultaneously: interference by HIV itself and the ARV drugs’ pharmacological effects as UPR activators. New evidence of how HIV modulates the UPR to enhance its own replication and secure infection success is also presented. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0298-0) contains supplementary material, which is available to authorized users.",2015 May 15,"['Borsa, Mariana', 'Ferreira, Pedro L. C.', 'Petry, Andrea', 'Ferreira, Luiz G. E.', 'Camargo, Maristela M.', 'Bou-Habib, Dumith Chequer', 'Pinto, Aguinaldo R.']",Virol J,,,True
dcc14fe9ac1567bcde8412180b20c71162525235,PMC,Expected and Unexpected Features of the Newly Discovered Bat Influenza A-like Viruses,http://dx.doi.org/10.1371/journal.ppat.1004819,PMC4456350,26042416,CC BY,,2015 Jun 4,"['Ma, Wenjun', 'García-Sastre, Adolfo', 'Schwemmle, Martin']",PLoS Pathog,,,True
0bca841af11fa978a07f916ec43b34d7c88b71c1,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,True
15cf10fbb4513d95421f82b181f09720341d6891,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
12cd0a1920578e381e2a512f33c628492498696f,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
6dc8d7760c9abdca8c46e9637b7c0d69b817e1c3,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
54289fb6b35fe32c9e402d7dbfbf8919c22fcc09,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
accf201367ac6c6c64efe39b028fe9dff59fbed1,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
f1b2dd5bd5cff41a9309d5bf4e7d00339f0d2b51,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
4139177a6f98a38d4f1f572f8cd30bec0d39aaf2,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
b43fe5da2851b777800977b9cc3a497ef7bd0cd2,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
c2ef66ab7ee23556b8bd5ea61bffc3dcde4a153b,PMC,A Recombinant Fungal Lectin for Labeling Truncated Glycans on Human Cancer Cells,http://dx.doi.org/10.1371/journal.pone.0128190,PMC4456360,26042789,CC BY,"Cell surface glycoconjugates present alterations of their structures in chronic diseases and distinct oligosaccharide epitopes have been associated with cancer. Among them, truncated glycans present terminal non-reducing β-N-acetylglucosamine (GlcNAc) residues that are rare on healthy tissues. Lectins from unconventional sources such as fungi or algi provide novel markers that bind specifically to such epitopes, but their availability may be challenging. A GlcNAc-binding lectin from the fruiting body of the fungus Psathyrella velutina (PVL) has been produced in good yield in bacterial culture. A strong specificity for terminal GlcNAc residues was evidenced by glycan array. Affinity values obtained by microcalorimetry and surface plasmon resonance demonstrated a micromolar affinity for GlcNAcβ1-3Gal epitopes and for biantennary N-glycans with GlcNAcβ1-2Man capped branches. Crystal structure of PVL complexed with GlcNAcβ1-3Gal established the structural basis of the specificity. Labeling of several types of cancer cells and use of inhibitors of glycan metabolism indicated that rPVL binds to terminal GlcNAc but also to sialic acid (Neu5Ac). Analysis of glycosyltransferase expression confirmed the higher amount of GlcNAc present on cancer cells. rPVL binding is specific to cancer tissue and weak or no labeling is observed for healthy ones, except for stomach glands that present unique αGlcNAc-presenting mucins. In lung, breast and colon carcinomas, a clear delineation could be observed between cancer regions and surrounding healthy tissues. PVL is therefore a useful tool for labeling agalacto-glycans in cancer or other diseases.",2015 Jun 4,"['Audfray, Aymeric', 'Beldjoudi, Mona', 'Breiman, Adrien', 'Hurbin, Amandine', 'Boos, Irene', 'Unverzagt, Carlo', 'Bouras, Mourad', 'Lantuejoul, Sylvie', 'Coll, Jean-Luc', 'Varrot, Annabelle', 'Le Pendu, Jacques', 'Busser, Benoit', 'Imberty, Anne']",PLoS One,,,False
ca6f9746b47f8fe6e187a867ad37502d950a3fbd,PMC,Integrated cluster- and case-based surveillance for detecting stage III zoonotic pathogens: an example of Nipah virus surveillance in Bangladesh,http://dx.doi.org/10.1017/S0950268814002635,PMC4456770,25342551,CC BY,"This paper explores the utility of cluster- and case-based surveillance established in government hospitals in Bangladesh to detect Nipah virus, a stage III zoonotic pathogen. Physicians listed meningo-encephalitis cases in the 10 surveillance hospitals and identified a cluster when ⩾2 cases who lived within 30 min walking distance of one another developed symptoms within 3 weeks of each other. Physicians collected blood samples from the clustered cases. As part of case-based surveillance, blood was collected from all listed meningo-encephalitis cases in three hospitals during the Nipah season (January–March). An investigation team visited clustered cases’ communities to collect epidemiological information and blood from the living cases. We tested serum using Nipah-specific IgM ELISA. Up to September 2011, in 5887 listed cases, we identified 62 clusters comprising 176 encephalitis cases. We collected blood from 127 of these cases. In 10 clusters, we identified a total of 62 Nipah cases: 18 laboratory-confirmed and 34 probable. We identified person-to-person transmission of Nipah virus in four clusters. From case-based surveillance, we identified 23 (4%) Nipah cases. Faced with thousands of encephalitis cases, integrated cluster surveillance allows targeted deployment of investigative resources to detect outbreaks by stage III zoonotic pathogens in resource-limited settings.",2015 Jul 24,"['NASER, A. M.', 'HOSSAIN, M. J.', 'SAZZAD, H. M. S.', 'HOMAIRA, N.', 'GURLEY, E. S.', 'PODDER, G.', 'AFROJ, S.', 'BANU, S.', 'ROLLIN, P. E.', 'DASZAK, P.', 'AHMED, B.-N.', 'RAHMAN, M.', 'LUBY, S. P.']",Epidemiol Infect,,,True
138200f99f62c51776c9afec55d856e854ea8ff1,PMC,Alternative Antigen Processing for MHC Class I: Multiple Roads Lead to Rome,http://dx.doi.org/10.3389/fimmu.2015.00298,PMC4457021,26097483,CC BY,"The well described conventional antigen-processing pathway is accountable for most peptides that end up in MHC class I molecules at the cell surface. These peptides experienced liberation by the proteasome and transport by the peptide transporter TAP. However, there are multiple roads that lead to Rome, illustrated by the increasing number of alternative processing pathways that have been reported during last years. Interestingly, TAP-deficient individuals do not succumb to viral infections, suggesting that CD8 T cell immunity is sufficiently supported by alternative TAP-independent processing pathways. To date, a diversity of viral and endogenous TAP-independent peptides have been identified in the grooves of different MHC class I alleles. Some of these peptides are not displayed by normal TAP-positive cells and we therefore called them TEIPP, for “T-cell epitopes associated with impaired peptide processing.” TEIPPs are hidden self-antigens, are derived from normal housekeeping proteins, and are processed via unconventional processing pathways. Per definition, TEIPPs are presented via TAP-independent pathways, but recent data suggest that part of this repertoire still depend on proteasome and metalloprotease activity. An exception is the C-terminal peptide of the endoplasmic reticulum (ER)-membrane-spanning ceramide synthase Trh4 that is surprisingly liberated by the signal peptide peptidase (SPP), the proteolytic enzyme involved in cleaving leader sequences. The intramembrane cleaving SPP is thereby an important contributor of TAP-independent peptides. Its family members, like the Alzheimer’s related presenilins, might contribute as well, according to our preliminary data. Finally, alternative peptide routing is an emerging field and includes processes like the unfolded protein response, the ER-associated degradation, and autophagy-associated vesicular pathways. These data convince us that there is a world to be discovered in the field of unconventional antigen processing.",2015 Jun 5,"['Oliveira, Cláudia C.', 'van Hall, Thorbald']",Front Immunol,,,True
27ed601fcd2be1e67274e57dcc4ea6b01040e5ec,PMC,A Sweet Spot for Molecular Diagnostics: Coupling Isothermal Amplification and Strand Exchange Circuits to Glucometers,http://dx.doi.org/10.1038/srep11039,PMC4458886,26050646,CC BY,"Strand exchange nucleic acid circuitry can be used to transduce isothermal nucleic acid amplification products into signals that can be readable on an off-the-shelf glucometer. Loop-mediated isothermal amplification (LAMP) is limited by the accumulation of non-specific products, but nucleic acid circuitry can be used to probe and distinguish specific amplicons. By combining this high temperature isothermal amplification method with a thermostable invertase, we can directly transduce Middle-East respiratory syndrome coronavirus and Zaire Ebolavirus templates into glucose signals, with a sensitivity as low as 20–100 copies/μl, equating to atto-molar (or low zepto-mole). Virus from cell lysates and synthetic templates could be readily amplified and detected even in sputum or saliva. An OR gate that coordinately triggered on viral amplicons further guaranteed fail-safe virus detection. The method describes has potential for accelerating point-of-care applications, in that biological samples could be applied to a transducer that would then directly interface with an off-the-shelf, approved medical device.",2015 Jun 8,"['Du, Yan', 'Hughes, Randall A.', 'Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Ellington, Andrew D.', 'Li, Bingling']",Sci Rep,,,True
ecef0f865903d77f2ffbe8cb1db275b7268ff77f,PMC,A Sweet Spot for Molecular Diagnostics: Coupling Isothermal Amplification and Strand Exchange Circuits to Glucometers,http://dx.doi.org/10.1038/srep11039,PMC4458886,26050646,CC BY,"Strand exchange nucleic acid circuitry can be used to transduce isothermal nucleic acid amplification products into signals that can be readable on an off-the-shelf glucometer. Loop-mediated isothermal amplification (LAMP) is limited by the accumulation of non-specific products, but nucleic acid circuitry can be used to probe and distinguish specific amplicons. By combining this high temperature isothermal amplification method with a thermostable invertase, we can directly transduce Middle-East respiratory syndrome coronavirus and Zaire Ebolavirus templates into glucose signals, with a sensitivity as low as 20–100 copies/μl, equating to atto-molar (or low zepto-mole). Virus from cell lysates and synthetic templates could be readily amplified and detected even in sputum or saliva. An OR gate that coordinately triggered on viral amplicons further guaranteed fail-safe virus detection. The method describes has potential for accelerating point-of-care applications, in that biological samples could be applied to a transducer that would then directly interface with an off-the-shelf, approved medical device.",2015 Jun 8,"['Du, Yan', 'Hughes, Randall A.', 'Bhadra, Sanchita', 'Jiang, Yu Sherry', 'Ellington, Andrew D.', 'Li, Bingling']",Sci Rep,,,True
95d3f266c79f401f0db216cf320eb2b28b5ed8b8,PMC,Effectiveness of non-pharmaceutical measures in preventing pediatric influenza: a case–control study,http://dx.doi.org/10.1186/s12889-015-1890-3,PMC4459072,26055522,CC BY,"BACKGROUND: Hygiene behavior plays a relevant role in infectious disease transmission. The aim of this study was to evaluate non-pharmaceutical interventions (NPI) in preventing pediatric influenza infections. METHODS: Laboratory confirmed influenza cases occurred during 2009–10 and 2010–11 seasons matched by age and date of consultation. NPI (frequency of hand washing, alcohol-based hand sanitizer use and hand washing after touching contaminated surfaces) during seven days prior to onset of symptoms were obtained from parents of cases and controls. RESULTS: Cases presented higher prevalence of underlying conditions such as pneumonia [OR = 3.23; 95 % CI: 1.38 – 7.58 p = 0.007], asthma [OR = 2.45; 95 % CI: 1.17 – 5.14 p = 0.02] and having more than 1 risk factor [OR = 1.67; 95 % CI: 0.99 – 2.82 p = 0.05]. Hand washing more than 5 times per day [aOR = 0.62; 95 % CI: 0.39 – 0.99 p = 0.04] was the only statistically significant protective factor. When considering two age groups (pre-school age 0–4 yrs and school age 5–17) yrs , only the school age group showed a negative association for influenza infection for both washing more than 5 times per day [aOR = 0.47; 95 % CI: 0.22 – 0.99 p = 0.04] and hand washing after touching contaminated surfaces [aOR = 0.19; 95 % CI: 0.04 – 0.86 p = 0.03]. CONCLUSION: Frequent hand washing should be recommended to prevent influenza infection in the community setting and in special in the school age group.",2015 Jun 9,"['Torner, Núria', 'Soldevila, Núria', 'Garcia, Juan Jose', 'Launes, Cristian', 'Godoy, Pere', 'Castilla, Jesús', 'Domínguez, Angela', None]",BMC Public Health,,,True
609c3b3465c19726b4777d17e3e2b19ca9de990b,PMC,Fecal virome analysis of three carnivores reveals a novel nodavirus and multiple gemycircularviruses,http://dx.doi.org/10.1186/s12985-015-0305-5,PMC4459443,25986582,CC BY,"BACKGROUND: More knowledge about viral populations in wild animals is needed in order to better understand and assess the risk of zoonotic diseases. In this study we performed viral metagenomic analysis of fecal samples from three healthy carnivores: a badger (Meles meles), a mongoose (Herpestes ichneumon) and an otter (Lutra lutra) from Portugal. RESULTS: We detected the presence of novel highly divergent viruses in the fecal material of the carnivores analyzed, such as five gemycircularviruses. Four of these gemycircularviruses were found in the mongoose and one in the badger. In addition we also identified an RNA-dependent RNA polymerase gene from a putative novel member of the Nodaviridae family in the fecal material of the otter. CONCLUSIONS: Together these results underline that many novel viruses are yet to be discovered and that fecal associated viruses are not always related to disease. Our study expands the knowledge of viral species present in the gut, although the interpretation of the true host species of such novel viruses needs to be reviewed with great caution.",2015 May 20,"['Conceição-Neto, Nádia', 'Zeller, Mark', 'Heylen, Elisabeth', 'Lefrère, Hanne', 'Mesquita, João Rodrigo', 'Matthijnssens, Jelle']",Virol J,,,True
af728043c4fdbde717229134e2cd8bada6760176,PMC,Development of a real-time reverse transcription loop-mediated isothermal amplification method for the rapid detection of porcine epidemic diarrhea virus,http://dx.doi.org/10.1186/s12985-015-0297-1,PMC4459462,25972083,CC BY,"BACKGROUND: Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease characterized by severe enteritis, vomiting and watery diarrhea in swine. Recently, the outbreak of the epidemic disease has been a serious problem in swine industry. The objective of this study is to develop a rapid, sensitive, and real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for the detection of porcine epidemic diarrhea virus (PEDV) in less equipped laboratories. RESULTS: The optimal reaction condition of the current real-time RT-LAMP for PEDV was 62 °C for 45 min. It was capable of detecting PEDV from clinical samples and differentiating PEDV from several related porcine viruses, while it did not require additional expensive equipment. The minimum detection limit of the real-time RT-LAMP assay was 0.07PFU per reaction for PEDV RNA, making this assay approximately 100-fold more sensitive than that of one-step RT-PCR. By screening a panel of clinical specimens, the results showed that this method presented a similar sensitivity with real-time RT-PCR and was somewhat sensitive than one-step RT-PCR in detection of clinical samples. CONCLUSIONS: In this study, we have developed a new real-time RT-LAMP method, which is rapid, sensitive and efficient to detect PEDV.This method holds great promises not only in laboratory detection and discrimination of PEDV but also in large scale field and clinical studies.",2015 May 14,"['Yu, Xuewu', 'Shi, Lin', 'Lv, Xiaoping', 'Yao, Wei', 'Cao, Minghui', 'Yu, Hanxun', 'Wang, Xiurong', 'Zheng, Shimin']",Virol J,,,True
c444840c3b5380002dea23e1e8598f545a3470a5,PMC,Genomic Analysis and Surveillance of the Coronavirus Dominant in Ducks in China,http://dx.doi.org/10.1371/journal.pone.0129256,PMC4459809,26053682,CC BY,"The genetic diversity, evolution, distribution, and taxonomy of some coronaviruses dominant in birds other than chickens remain enigmatic. In this study we sequenced the genome of a newly identified coronavirus dominant in ducks (DdCoV), and performed a large-scale surveillance of coronaviruses in chickens and ducks using a conserved RT-PCR assay. The viral genome harbors a tandem repeat which is rare in vertebrate RNA viruses. The repeat is homologous to some proteins of various cellular organisms, but its origin remains unknown. Many substitutions, insertions, deletions, and some frameshifts and recombination events have occurred in the genome of the DdCoV, as compared with the coronavirus dominant in chickens (CdCoV). The distances between DdCoV and CdCoV are large enough to separate them into different species within the genus Gammacoronavirus. Our surveillance demonstrated that DdCoVs and CdCoVs belong to different lineages and occupy different ecological niches, further supporting that they should be classified into different species. Our surveillance also demonstrated that DdCoVs and CdCoVs are prevalent in live poultry markets in some regions of China. In conclusion, this study shed novel insight into the genetic diversity, evolution, distribution, and taxonomy of the coronaviruses circulating in chickens and ducks.",2015 Jun 8,"['Zhuang, Qing-Ye', 'Wang, Kai-Cheng', 'Liu, Shuo', 'Hou, Guang-Yu', 'Jiang, Wen-Ming', 'Wang, Su-Chun', 'Li, Jin-Ping', 'Yu, Jian-Min', 'Chen, Ji-Ming']",PLoS One,,,True
f3cbc0503581249a834895fc94cd3bae24714a0d,PMC,Which Kind of Provider’s Operation Volumes Matters? Associations between CABG Surgical Site Infection Risk and Hospital and Surgeon Operation Volumes among Medical Centers in Taiwan,http://dx.doi.org/10.1371/journal.pone.0129178,PMC4459823,26053035,CC BY,"BACKGROUND: Volume-infection relationships have been examined for high-risk surgical procedures, but the conclusions remain controversial. The inconsistency might be due to inaccurate identification of cases of infection and different methods of categorizing service volumes. This study takes coronary artery bypass graft (CABG) surgical site infections (SSIs) as an example to examine whether a relationship exists between operation volumes and SSIs, when different SSIs case identification, definitions and categorization methods of operation volumes were implemented. METHODS: A population-based cross-sectional multilevel study was conducted. A total of 7,007 patients who received CABG surgery between 2006 and 2008 from19 medical centers in Taiwan were recruited. SSIs associated with CABG surgery were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9 CM) codes and a Classification and Regression Trees (CART) model. Two definitions of surgeon and hospital operation volumes were used: (1) the cumulative CABG operation volumes within the study period; and (2) the cumulative CABG operation volumes in the previous one year before each CABG surgery. Operation volumes were further treated in three different ways: (1) a continuous variable; (2) a categorical variable based on the quartile; and (3) a data-driven categorical variable based on k-means clustering algorithm. Furthermore, subgroup analysis for comorbidities was also conducted. RESULTS: This study showed that hospital volumes were not significantly associated with SSIs, no matter which definitions or categorization methods of operation volume, or SSIs case identification approaches were used. On the contrary, the relationships between surgeon’s volumes varied. Most of the models demonstrated that the low-volume surgeons had higher risk than high-volume surgeons. CONCLUSION: Surgeon volumes were more important than hospital volumes in exploring the relationship between CABG operation volumes and SSIs in Taiwan. However, the relationships were not robust. Definitions and categorization methods of operation volume and correct identification of SSIs are important issues for future research.",2015 Jun 8,"['Yu, Tsung-Hsien', 'Tung, Yu-Chi', 'Chung, Kuo-Piao']",PLoS One,,,True
f0b1fa4036434b57c8307d43c39a4193f7e8053a,PMC,The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model,http://dx.doi.org/10.1371/journal.pone.0128794,PMC4459876,26053018,CC BY,"BACKGROUND: Carrageenan is a clinically proven and marketed compound for the treatment of viral upper respiratory tract infections. As infections caused by influenza virus are often accompanied by infections with other respiratory viruses the combination of a specific anti-influenza compound with the broadly active antiviral polymer has huge potential for the treatment of respiratory infections. Thus, the combination of the specific anti-influenza drug Zanamivir together with carrageenan in a formulation suitable for intranasal application was evaluated in-vitro and in-vivo. PRINCIPAL FINDINGS: We show in-vitro that carrageenan and Zanamivir act synergistically against several influenza A virus strains (H1N1(09)pdm, H3N2, H5N1, H7N7). Moreover, we demonstrate in a lethal influenza model with a low pathogenic H7N7 virus (HA closely related to the avian influenza A(H7N9) virus) and a H1N1(09)pdm influenza virus in C57BL/6 mice that the combined use of both compounds significantly increases survival of infected animals in comparison with both mono-therapies or placebo. Remarkably, this benefit is maintained even when the treatment starts up to 72 hours post infection. CONCLUSION: A nasal spray containing carrageenan and Zanamivir should therefore be tested for prevention and treatment of uncomplicated influenza in clinical trials.",2015 Jun 8,"['Morokutti-Kurz, Martina', 'König-Schuster, Marielle', 'Koller, Christiane', 'Graf, Christine', 'Graf, Philipp', 'Kirchoff, Norman', 'Reutterer, Benjamin', 'Seifert, Jan-Marcus', 'Unger, Hermann', 'Grassauer, Andreas', 'Prieschl-Grassauer, Eva', 'Nakowitsch, Sabine']",PLoS One,,,True
90403742f692b74ea175eef945ff8560a1a6c2b5,PMC,DNA transducer-triggered signal switch for visual colorimetric bioanalysis,http://dx.doi.org/10.1038/srep11190,PMC4462091,26060886,CC BY,"A simple and versatile colorimetric biosensor has been developed for sensitive and specific detection of a wide range of biomolecules, such as oligonucleotides and aptamer-recognized targets. Combining the signal transducer and catalyzed hairpin assembly (CHA)-based signal amplification, the target DNA binds with the hairpin DNA to form a new nucleic acid sequence and creates a toehold in the transducer for initiating the recycle amplification reaction of CHA. The catalyzed assembly process produces a large amount of G-rich DNA. In the presence of hemin, the G-rich DNA forms G-quadruplex/hemin complex and mimic horseradish peroxidase activity, which catalyzes a colorimetric reaction. Under optimal conditions, the calibration curve of synthetic target DNA has good linearity from 50 pM to 200 nM with a detection limit of 32 pM. This strategy has been successfully applied to detect S. pneumoniae as low as 156 CFU mL(−1), and shows a good specificity against closely related streptococci and major pathogenic bacteria. In addition, the developed method enables successful visual analysis of S. pneumoniae in clinical samples by the naked eye. Importantly, this method demonstrates excellent assay versatility for sensitively detecting oligonucleotides or aptamer-recognized targets.",2015 Jun 10,"['Chen, Wenhong', 'Yan, Yurong', 'Zhang, Ye', 'Zhang, Xuemei', 'Yin, Yibing', 'Ding, Shijia']",Sci Rep,,,True
2405180506967da1f4007e49ad653c3c356a823a,PMC,LeishVet update and recommendations on feline leishmaniosis,http://dx.doi.org/10.1186/s13071-015-0909-z,PMC4462189,26041555,CC BY,"Limited data is available on feline leishmaniosis (FeL) caused by Leishmania infantum worldwide. The LeishVet group presents in this report a review of the current knowledge on FeL, the epidemiological role of the cat in L. infantum infection, clinical manifestations, and recommendations on diagnosis, treatment and monitoring, prognosis and prevention of infection, in order to standardize the management of this disease in cats. The consensus of opinions and recommendations was formulated by combining a comprehensive review of evidence-based studies and case reports, clinical experience and critical consensus discussions. While subclinical feline infections are common in areas endemic for canine leishmaniosis, clinical illness due to L. infantum in cats is rare. The prevalence rates of feline infection with L. infantum in serological or molecular-based surveys range from 0 % to more than 60 %. Cats are able to infect sand flies and, therefore, they may act as a secondary reservoir, with dogs being the primary natural reservoir. The most common clinical signs and clinicopathological abnormalities compatible with FeL include lymph node enlargement and skin lesions such as ulcerative, exfoliative, crusting or nodular dermatitis (mainly on the head or distal limbs), ocular lesions (mainly uveitis), feline chronic gingivostomatitis syndrome, mucocutaneous ulcerative or nodular lesions, hypergammaglobulinaemia and mild normocytic normochromic anaemia. Clinical illness is frequently associated with impaired immunocompetence, as in case of retroviral coinfections or immunosuppressive therapy. Diagnosis is based on serology, polymerase chain reaction (PCR), cytology, histology, immunohistochemistry (IHC) or culture. If serological testing is negative or low positive in a cat with clinical signs compatible with FeL, the diagnosis of leishmaniosis should not be excluded and additional diagnostic methods (cytology, histology with IHC, PCR, culture) should be employed. The most common treatment used is allopurinol. Meglumine antimoniate has been administered in very few reported cases. Both drugs are administered alone and most cats recover clinically after therapy. Follow-up of treated cats with routine laboratory tests, serology and PCR is essential for prevention of clinical relapses. Specific preventative measures for this infection in cats are currently not available.",2015 Jun 4,"['Pennisi, Maria-Grazia', 'Cardoso, Luís', 'Baneth, Gad', 'Bourdeau, Patrick', 'Koutinas, Alek', 'Miró, Guadalupe', 'Oliva, Gaetano', 'Solano-Gallego, Laia']",Parasit Vectors,,,True
4b2ef217cb3fedccaffa0ecdd43344810630987b,PMC,Identification of human leukemia antigen A*0201-restricted epitopes derived from epidermal growth factor pathway substrate number 8,http://dx.doi.org/10.3892/mmr.2015.3673,PMC4463842,25936538,CC BY,"T-cell-mediated immunotherapy of hematological malignancies requires selection of targeted tumor-associated antigens and T-cell epitopes contained in these tumor proteins. Epidermal growth factor receptor pathway substrate 8 (EPS8), whose function is pivotal for tumor proliferation, progression and metastasis, has been found to be overexpressed in most human tumor types, while its expression in normal tissue is low. The aim of the present study was to identify human leukemia antigen (HLA)-A*0201-restricted epitopes of EPS8 by using a reverse immunology approach. To achieve this, computer algorithms were used to predict HLA-A*0201 molecular binding, proteasome cleavage patterns as well as translocation of transporters associated with antigen processing. Candidate peptides were experimentally validated by T2 binding affinity assay and brefeldin-A decay assay. The functional avidity of peptide-specific cytotoxic T lymphocytes (CTLs) induced from peripheral blood mononuclear cells of healthy volunteers were evaluated by using an enzyme-linked immunosorbent spot assay and a cytotoxicity assay. Four peptides, designated as P455, P92, P276 and P360, had high affinity and stability of binding towards the HLA-A*0201 molecule, and specific CTLs induced by them significantly responded to the corresponding peptides and secreted IFN-γ. At the same time, the CTLs were able to specifically lyse EPS8-expressing cell lines in an HLA-A*0201-restricted manner. The present study demon-strated that P455, P92, P276 and P360 were CTL epitopes of EPS8, and were able to be used for epitope-defined adoptive T-cell transfer and multi-epitope-based vaccine design.",2015 Aug 23,"['TANG, BAISHAN', 'ZHOU, WEIJUN', 'DU, JINGWEN', 'HE, YANJIE', 'LI, YUHUA']",Mol Med Rep,,,True
5f8c204d73feaf62ba6caa3be033d007e3134d5a,PMC,Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System,http://dx.doi.org/10.1038/srep11123,PMC4464075,26068176,CC BY,"Dietary fats and sodium are both palatable and are hypothesized to synergistically contribute to ingestive behavior and thereby obesity. Contrary to this hypothesis, C57BL/6J mice fed a 45% high fat diet exhibited weight gain that was inhibited by increased dietary sodium content. This suppressive effect of dietary sodium upon weight gain was mediated specifically through a reduction in digestive efficiency, with no effects on food intake behavior, physical activity, or resting metabolism. Replacement of circulating angiotensin II levels reversed the effects of high dietary sodium to suppress digestive efficiency. While the AT(1) receptor antagonist losartan had no effect in mice fed low sodium, the AT(2) receptor antagonist PD-123,319 suppressed digestive efficiency. Correspondingly, genetic deletion of the AT(2) receptor in FVB/NCrl mice resulted in suppressed digestive efficiency even on a standard chow diet. Together these data underscore the importance of digestive efficiency in the pathogenesis of obesity, and implicate dietary sodium, the renin-angiotensin system, and the AT(2) receptor in the control of digestive efficiency regardless of mouse strain or macronutrient composition of the diet. These findings highlight the need for greater understanding of nutrient absorption control physiology, and prompt more uniform assessment of digestive efficiency in animal studies of energy balance.",2015 Jun 11,"['Weidemann, Benjamin J.', 'Voong, Susan', 'Morales-Santiago, Fabiola I.', 'Kahn, Michael Z.', 'Ni, Jonathan', 'Littlejohn, Nicole K.', 'Claflin, Kristin E.', 'Burnett, Colin M.L.', 'Pearson, Nicole A.', 'Lutter, Michael L.', 'Grobe, Justin L.']",Sci Rep,,,True
0431672907f81802938cf3dd43fe76682469524d,PMC,Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System,http://dx.doi.org/10.1038/srep11123,PMC4464075,26068176,CC BY,"Dietary fats and sodium are both palatable and are hypothesized to synergistically contribute to ingestive behavior and thereby obesity. Contrary to this hypothesis, C57BL/6J mice fed a 45% high fat diet exhibited weight gain that was inhibited by increased dietary sodium content. This suppressive effect of dietary sodium upon weight gain was mediated specifically through a reduction in digestive efficiency, with no effects on food intake behavior, physical activity, or resting metabolism. Replacement of circulating angiotensin II levels reversed the effects of high dietary sodium to suppress digestive efficiency. While the AT(1) receptor antagonist losartan had no effect in mice fed low sodium, the AT(2) receptor antagonist PD-123,319 suppressed digestive efficiency. Correspondingly, genetic deletion of the AT(2) receptor in FVB/NCrl mice resulted in suppressed digestive efficiency even on a standard chow diet. Together these data underscore the importance of digestive efficiency in the pathogenesis of obesity, and implicate dietary sodium, the renin-angiotensin system, and the AT(2) receptor in the control of digestive efficiency regardless of mouse strain or macronutrient composition of the diet. These findings highlight the need for greater understanding of nutrient absorption control physiology, and prompt more uniform assessment of digestive efficiency in animal studies of energy balance.",2015 Jun 11,"['Weidemann, Benjamin J.', 'Voong, Susan', 'Morales-Santiago, Fabiola I.', 'Kahn, Michael Z.', 'Ni, Jonathan', 'Littlejohn, Nicole K.', 'Claflin, Kristin E.', 'Burnett, Colin M.L.', 'Pearson, Nicole A.', 'Lutter, Michael L.', 'Grobe, Justin L.']",Sci Rep,,,False
edcbcb53bfb68a6600dc092b57cf09b2a77ac86e,PMC,Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study,http://dx.doi.org/10.1371/journal.ppat.1004869,PMC4466531,26070066,CC0,"To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates.",2015 Jun 12,"['Zhai, Yijie', 'Franco, Luis M.', 'Atmar, Robert L.', 'Quarles, John M.', 'Arden, Nancy', 'Bucasas, Kristine L.', 'Wells, Janet M.', 'Niño, Diane', 'Wang, Xueqing', 'Zapata, Gladys E.', 'Shaw, Chad A.', 'Belmont, John W.', 'Couch, Robert B.']",PLoS Pathog,,,True
737e13b0236c1e2a6ada9c31ad3d8987a559b244,PMC,High Pulmonary Levels of IL-6 and IL-1β in Children with Chronic Suppurative Lung Disease Are Associated with Low Systemic IFN-γ Production in Response to Non-Typeable Haemophilus influenzae,http://dx.doi.org/10.1371/journal.pone.0129517,PMC4466570,26066058,CC BY,"Non-typeable Haemophilus influenzae (NTHi) is commonly associated with chronic suppurative lung disease in children. We have previously shown that children with chronic suppurative lung disease have a reduced capacity to produce IFN-γ in response to NTHi compared with healthy control children. The aim of this study was to determine if deficient NTHi-specific IFN-γ production is associated with heightened systemic or airway inflammation. We measured a panel of cytokines (IFN-γ, IL-1β, IL-6, IL-8, IL-12 p70), antimicrobial proteins (LL-37, IP-10) as well as cellular and clinical factors associated with airway and systemic inflammation in 70 children with chronic suppurative lung disease. IFN-γ was measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. Regression analysis was used to assess the association between the systemic and airway inflammation and the capacity to produce IFN-γ. On multivariate regression, NTHi-specific IFN-γ production was significantly negatively associated with the BAL concentrations of the inflammatory cytokines IL-6 (β=-0.316; 95%CI -0.49, -0.14; p=0.001) and IL-1β (β=-0.023; 95%CI -0.04, -0.01; p=0.001). This association was independent of bacterial or viral infection, BAL cellularity and the severity of bronchiectasis (using modified Bhalla score on chest CT scans). We found limited evidence of systemic inflammation in children with chronic suppurative lung disease. In summary, increased local airway inflammation is associated with a poorer systemic cell-mediated immune response to NTHi in children with chronic suppurative lung disease. These data support the emerging body of evidence that impaired cell-mediated immune responses and dysregulated airway inflammation may be linked and contribute to the pathobiology of chronic suppurative lung disease.",2015 Jun 12,"['Pizzutto, Susan J.', 'Upham, John W.', 'Yerkovich, Stephanie T.', 'Chang, Anne B.']",PLoS One,,,True
6331b16803abd3819dba628d339ffadbd2ad9a84,PMC,High Pulmonary Levels of IL-6 and IL-1β in Children with Chronic Suppurative Lung Disease Are Associated with Low Systemic IFN-γ Production in Response to Non-Typeable Haemophilus influenzae,http://dx.doi.org/10.1371/journal.pone.0129517,PMC4466570,26066058,CC BY,"Non-typeable Haemophilus influenzae (NTHi) is commonly associated with chronic suppurative lung disease in children. We have previously shown that children with chronic suppurative lung disease have a reduced capacity to produce IFN-γ in response to NTHi compared with healthy control children. The aim of this study was to determine if deficient NTHi-specific IFN-γ production is associated with heightened systemic or airway inflammation. We measured a panel of cytokines (IFN-γ, IL-1β, IL-6, IL-8, IL-12 p70), antimicrobial proteins (LL-37, IP-10) as well as cellular and clinical factors associated with airway and systemic inflammation in 70 children with chronic suppurative lung disease. IFN-γ was measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. Regression analysis was used to assess the association between the systemic and airway inflammation and the capacity to produce IFN-γ. On multivariate regression, NTHi-specific IFN-γ production was significantly negatively associated with the BAL concentrations of the inflammatory cytokines IL-6 (β=-0.316; 95%CI -0.49, -0.14; p=0.001) and IL-1β (β=-0.023; 95%CI -0.04, -0.01; p=0.001). This association was independent of bacterial or viral infection, BAL cellularity and the severity of bronchiectasis (using modified Bhalla score on chest CT scans). We found limited evidence of systemic inflammation in children with chronic suppurative lung disease. In summary, increased local airway inflammation is associated with a poorer systemic cell-mediated immune response to NTHi in children with chronic suppurative lung disease. These data support the emerging body of evidence that impaired cell-mediated immune responses and dysregulated airway inflammation may be linked and contribute to the pathobiology of chronic suppurative lung disease.",2015 Jun 12,"['Pizzutto, Susan J.', 'Upham, John W.', 'Yerkovich, Stephanie T.', 'Chang, Anne B.']",PLoS One,,,False
58a3c6aa227536fce49882de52254d61c1a6a0e2,PMC,High Pulmonary Levels of IL-6 and IL-1β in Children with Chronic Suppurative Lung Disease Are Associated with Low Systemic IFN-γ Production in Response to Non-Typeable Haemophilus influenzae,http://dx.doi.org/10.1371/journal.pone.0129517,PMC4466570,26066058,CC BY,"Non-typeable Haemophilus influenzae (NTHi) is commonly associated with chronic suppurative lung disease in children. We have previously shown that children with chronic suppurative lung disease have a reduced capacity to produce IFN-γ in response to NTHi compared with healthy control children. The aim of this study was to determine if deficient NTHi-specific IFN-γ production is associated with heightened systemic or airway inflammation. We measured a panel of cytokines (IFN-γ, IL-1β, IL-6, IL-8, IL-12 p70), antimicrobial proteins (LL-37, IP-10) as well as cellular and clinical factors associated with airway and systemic inflammation in 70 children with chronic suppurative lung disease. IFN-γ was measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. Regression analysis was used to assess the association between the systemic and airway inflammation and the capacity to produce IFN-γ. On multivariate regression, NTHi-specific IFN-γ production was significantly negatively associated with the BAL concentrations of the inflammatory cytokines IL-6 (β=-0.316; 95%CI -0.49, -0.14; p=0.001) and IL-1β (β=-0.023; 95%CI -0.04, -0.01; p=0.001). This association was independent of bacterial or viral infection, BAL cellularity and the severity of bronchiectasis (using modified Bhalla score on chest CT scans). We found limited evidence of systemic inflammation in children with chronic suppurative lung disease. In summary, increased local airway inflammation is associated with a poorer systemic cell-mediated immune response to NTHi in children with chronic suppurative lung disease. These data support the emerging body of evidence that impaired cell-mediated immune responses and dysregulated airway inflammation may be linked and contribute to the pathobiology of chronic suppurative lung disease.",2015 Jun 12,"['Pizzutto, Susan J.', 'Upham, John W.', 'Yerkovich, Stephanie T.', 'Chang, Anne B.']",PLoS One,,,False
ae7835c99d1391c53fec8da5b13783ebdd195223,PMC,Integrated travel network model for studying epidemics: Interplay between journeys and epidemic,http://dx.doi.org/10.1038/srep11401,PMC4466778,26073191,CC BY,"The ease of travelling between cities has contributed much to globalization. Yet, it poses a threat on epidemic outbreaks. It is of great importance for network science and health control to understand the impact of frequent journeys on epidemics. We stress that a new framework of modelling that takes a traveller’s viewpoint is needed. Such integrated travel network (ITN) model should incorporate the diversity among links as dictated by the distances between cities and different speeds of different modes of transportation, diversity among nodes as dictated by the population and the ease of travelling due to infrastructures and economic development of a city, and round-trip journeys to targeted destinations via the paths of shortest travel times typical of human journeys. An example is constructed for 116 cities in China with populations over one million that are connected by high-speed train services and highways. Epidemic spread on the constructed network is studied. It is revealed both numerically and theoretically that the traveling speed and frequency are important factors of epidemic spreading. Depending on the infection rate, increasing the traveling speed would result in either an enhanced or suppressed epidemic, while increasing the traveling frequency enhances the epidemic spreading.",2015 Jun 15,"['Ruan, Zhongyuan', 'Wang, Chaoqing', 'Ming Hui, Pak', 'Liu, Zonghua']",Sci Rep,,,True
cec3e151f7ac8b3a8766ac9fbc08c9429eaed31c,PMC,Integrated travel network model for studying epidemics: Interplay between journeys and epidemic,http://dx.doi.org/10.1038/srep11401,PMC4466778,26073191,CC BY,"The ease of travelling between cities has contributed much to globalization. Yet, it poses a threat on epidemic outbreaks. It is of great importance for network science and health control to understand the impact of frequent journeys on epidemics. We stress that a new framework of modelling that takes a traveller’s viewpoint is needed. Such integrated travel network (ITN) model should incorporate the diversity among links as dictated by the distances between cities and different speeds of different modes of transportation, diversity among nodes as dictated by the population and the ease of travelling due to infrastructures and economic development of a city, and round-trip journeys to targeted destinations via the paths of shortest travel times typical of human journeys. An example is constructed for 116 cities in China with populations over one million that are connected by high-speed train services and highways. Epidemic spread on the constructed network is studied. It is revealed both numerically and theoretically that the traveling speed and frequency are important factors of epidemic spreading. Depending on the infection rate, increasing the traveling speed would result in either an enhanced or suppressed epidemic, while increasing the traveling frequency enhances the epidemic spreading.",2015 Jun 15,"['Ruan, Zhongyuan', 'Wang, Chaoqing', 'Ming Hui, Pak', 'Liu, Zonghua']",Sci Rep,,,False
ff6f7ec41fcfb1353aea25253c33ae25469f6a07,PMC,Risky Bodies in the Plasma Bioeconomy: A Feminist Analysis,http://dx.doi.org/10.1177/1357034X13520331,PMC4467286,26097401,CC BY,"In 2003 the UK National Blood Service introduced a policy of ‘male donor preference’ which involved women’s plasma being discarded following blood collection. The policy was based on the view that data relating to the incidence of Transfusion-Related Acute Lung Injury (TRALI) was linked to transfusion with women’s plasma. While appearing to treat female donors as equal to male donors, exclusion criteria operate after donation at the stage of processing blood, thus perpetuating myths of universality even though only certain ‘extractions’ from women are retained for use in transfusion. Many women in the UK receive a plasma-derived product called Anti-D immunoglobulin which is manufactured from pooled male plasma. This article examines ways in which gender has significance for understanding blood relations, and how the blood economy is gendered. In our study of relations between blood donors and recipients, we explore how gendered bodies are produced through the discursive and material practices within blood services. We examine both how donation policies and the manufacturing and use of blood products produces gendered blood relations.",2015 Mar,"['Kent, Julie', 'Farrell, Anne-Maree']",Body Soc,,,True
05f2d4c337413ae496e31e2259020f3e328dcfa1,PMC,Recombinase Polymerase Amplification Assay for Rapid Diagnostics of Dengue Infection,http://dx.doi.org/10.1371/journal.pone.0129682,PMC4468249,26075598,CC BY,"BACKGROUND: Over 2.5 billion people are exposed to the risk of contracting dengue fever (DF). Early diagnosis of DF helps to diminish its burden on public health. Real-time reverse transcription polymerase amplification assays (RT-PCR) are the standard method for molecular detection of the dengue virus (DENV). Real-time RT-PCR analysis is not suitable for on-site screening since mobile devices are large, expensive, and complex. In this study, two RT-recombinase polymerase amplification (RT-RPA) assays were developed to detect DENV1-4. METHODOLOGY/PRINCIPAL FINDINGS: Using two quantitative RNA molecular standards, the analytical sensitivity of a RT-RPA targeting the 3´non-translated region of DENV1-4 was found to range from 14 (DENV4) to 241 (DENV1-3) RNA molecules detected. The assay was specific and did not cross detect other Flaviviruses. The RT-RPA assay was tested in a mobile laboratory combining magnetic-bead based total nucleic acid extraction and a portable detection device in Kedougou (Senegal) and in Bangkok (Thailand). In Kedougou, the RT-RPA was operated at an ambient temperature of 38°C with auxiliary electricity tapped from a motor vehicle and yielded a clinical sensitivity and specificity of 98% (n=31) and 100% (n=23), respectively. While in the field trial in Bangkok, the clinical sensitivity and specificity were 72% (n=90) and 100%(n=41), respectively. CONCLUSIONS/SIGNIFICANCE: During the first 5 days of infection, the developed DENV1-4 RT-RPA assays constitute a suitable accurate and rapid assay for DENV diagnosis. Moreover, the use of a portable fluorescence-reading device broadens its application potential to the point-of-care for outbreak investigations.",2015 Jun 15,"['Abd El Wahed, Ahmed', 'Patel, Pranav', 'Faye, Oumar', 'Thaloengsok, Sasikanya', 'Heidenreich, Doris', 'Matangkasombut, Ponpan', 'Manopwisedjaroen, Khajohnpong', 'Sakuntabhai, Anavaj', 'Sall, Amadou A.', 'Hufert, Frank T.', 'Weidmann, Manfred']",PLoS One,,,True
43c284998733a1d7cc474d14c378f08e4b509c63,PMC,Antiviral activity of silymarin against chikungunya virus,http://dx.doi.org/10.1038/srep11421,PMC4468427,26078201,CC BY,"The mosquito-borne chikungunya virus (CHIKV) causes chikungunya fever, with clinical presentations such as severe back and small joint pain, and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of three types of flavonoids against CHIKV in vitro replication. Three compounds: silymarin, quercetin and kaempferol were evaluated for their in vitro antiviral activities against CHIKV using a CHIKV replicon cell line and clinical isolate of CHIKV of Central/East African genotype. A cytopathic effect inhibition assay was used to determine their activities on CHIKV viral replication and quantitative reverse transcription PCR was used to calculate virus yield. Antiviral activity of effective compound was further investigated by evaluation of CHIKV protein expression using western blotting for CHIKV nsP1, nsP3, and E2E1 proteins. Briefly, silymarin exhibited significant antiviral activity against CHIKV, reducing both CHIKV replication efficiency and down-regulating production of viral proteins involved in replication. This study may have important consequence for broaden the chance of getting the effective antiviral for CHIKV infection.",2015 Jun 16,"['Lani, Rafidah', 'Hassandarvish, Pouya', 'Chiam, Chun Wei', 'Moghaddam, Ehsan', 'Chu, Justin Jang Hann', 'Rausalu, Kai', 'Merits, Andres', 'Higgs, Stephen', 'Vanlandingham, Dana', 'Abu Bakar, Sazaly', 'Zandi, Keivan']",Sci Rep,,,True
6a3acbb2d3cf75b9cb9221b0d8acc32559ec4cf8,PMC,Apolipoprotein D Transgenic Mice Develop Hepatic Steatosis through Activation of PPARγ and Fatty Acid Uptake,http://dx.doi.org/10.1371/journal.pone.0130230,PMC4470830,26083030,CC BY,"Transgenic mice (Tg) overexpressing human apolipoprotein D (H-apoD) in the brain are resistant to neurodegeneration. Despite the use of a neuron-specific promoter to generate the Tg mice, they expressed significant levels of H-apoD in both plasma and liver and they slowly develop hepatic steatosis and insulin resistance. We show here that hepatic PPARγ expression in Tg mice is increased by 2-fold compared to wild type (WT) mice. Consequently, PPARγ target genes Plin2 and Cide A/C are overexpressed, leading to increased lipid droplets formation. Expression of the fatty acid transporter CD36, another PPARgamma target, is also increased in Tg mice associated with elevated fatty acid uptake as measured in primary hepatocytes. Elevated expression of AMPK in the liver of Tg leads to phosphorylation of acetyl CoA carboxylase, indicating a decreased activity of the enzyme. Fatty acid synthase expression is also induced but the hepatic lipogenesis measured in vivo is not significantly different between WT and Tg mice. In addition, expression of carnitine palmitoyl transferase 1, the rate-limiting enzyme of beta-oxidation, is slightly upregulated. Finally, we show that overexpressing H-apoD in HepG2 cells in presence of arachidonic acid (AA), the main apoD ligand, increases the transcriptional activity of PPARγ. Supporting the role of apoD in AA transport, we observed enrichment in hepatic AA and a decrease in plasmatic AA concentration. Taken together, our results demonstrate that the hepatic steatosis observed in apoD Tg mice is a consequence of increased PPARγ transcriptional activity by AA leading to increased fatty acid uptake by the liver.",2015 Jun 17,"['Labrie, Marilyne', 'Lalonde, Simon', 'Najyb, Ouafa', 'Thiery, Maxime', 'Daneault, Caroline', 'Des Rosiers, Chrisitne', 'Rassart, Eric', 'Mounier, Catherine']",PLoS One,,,True
d3adf3be72d751812577d37b2f3db193b2b93cc2,PMC,"Alternative divalent cations (Zn(2+), Co(2+), and Mn(2+)) are not mutagenic at conditions optimal for HIV-1 reverse transcriptase activity",http://dx.doi.org/10.1186/s12858-015-0041-x,PMC4472245,25934642,CC BY,"BACKGROUND: Fidelity of DNA polymerases can be influenced by cation co-factors. Physiologically, Mg(2+) is used as a co-factor by HIV reverse transcriptase (RT) to perform catalysis; however, alternative cations including Mn(2+), Co(2+), and Zn(2+) can also support catalysis. Although Zn(2+) supports DNA synthesis, it inhibits HIV RT by significantly modifying RT catalysis. Zn(2+) is currently being investigated as a component of novel treatment options against HIV and we wanted to investigate the fidelity of RT with Zn(2+). METHODS: We used PCR-based and plasmid-based alpha complementation assays as well as steady-state misinsertion and misincorporation assays to examine the fidelity of RT with Mn(2+), Co(2+), and Zn(2+). RESULTS: The fidelity of DNA synthesis by HIV-1 RT was approximately 2.5 fold greater in Zn(2+) when compared to Mg(2+) at cation conditions optimized for nucleotide catalysis. Consistent with this, RT extended primers with mismatched 3′ nucleotides poorly and inserted incorrect nucleotides less efficiently using Zn(2+) than Mg(2+). In agreement with previous literature, we observed that Mn(2+) and Co(2+) dramatically decreased the fidelity of RT at highly elevated concentrations (6 mM). However, surprisingly, the fidelity of HIV RT with Mn(2+) and Co(2+) remained similar to Mg(2+) at lower concentrations that are optimal for catalysis. CONCLUSION: This study shows that Zn(2+), at optimal extension conditions, increases the fidelity of HIV-1 RT and challenges the notion that alternative cations capable of supporting polymerase catalysis are inherently mutagenic.",2015 May 3,"['Achuthan, Vasudevan', 'DeStefano, Jeffrey J']",BMC Biochem,,,True
51c863bc37f993b3da543b91458e3ed5abd9aba9,PMC,Pathology in Captive Wild Felids at German Zoological Gardens,http://dx.doi.org/10.1371/journal.pone.0130573,PMC4472349,26086731,CC BY,"This retrospective study provides an overview on spontaneous diseases occurring in 38 captive wild felids submitted for necropsy by German zoological gardens between 2004 and 2013. Species included 18 tigers, 8 leopards, 7 lions, 3 cheetahs and 2 cougars with an age ranging from 0.5 to 22 years. Renal lesions, predominantly tubular alterations (intra-tubular concrements, tubular degeneration, necrosis, intra-tubular cellular debris, proteinaceous casts, dilated tubuli) followed by interstitial (lympho-plasmacytic inflammation, fibrosis, metastatic-suppurative inflammation, eosinophilic inflammation) and glomerular lesions (glomerulonephritis, glomerulosclerosis, amyloidosis) were detected in 33 out of 38 animals (87%). Tumors were found in 19 of 38 felids (50%) with 12 animals showing more than one neoplasm. The tumor prevalence increased with age. Neoplasms originated from endocrine (11), genital (8), lympho-hematopoietic (5) and alimentary organs (4) as well as the mesothelium (3). Most common neoplasms comprised uterine/ovarian leiomyomas (5/2), thyroid adenomas/adenocarcinoma (5/1), pleural mesotheliomas (3), hemangiosarcomas (2) and glossal papillomas (2). Inflammatory changes were frequently encountered in the intestine and the lung. Two young animals displayed metastatic mineralization suggestive of a vitamin D- or calcium intoxication. One tiger exhibited degenerative white matter changes consistent with an entity termed large felid leukoencephalomyelopathy. Various hyperplastic, degenerative and inflammatory changes with minor clinical significance were found in several organs. Summarized, renal lesions followed by neoplastic changes as well as inflammatory changes in lung and gastrointestinal tract represent the most frequent findings in captive wild felids living in German zoological gardens.",2015 Jun 18,"['Junginger, Johannes', 'Hansmann, Florian', 'Herder, Vanessa', 'Lehmbecker, Annika', 'Peters, Martin', 'Beyerbach, Martin', 'Wohlsein, Peter', 'Baumgärtner, Wolfgang']",PLoS One,,,True
710a40e33a20fe517c78c06748005fea78f21105,PMC,Chloroquine and beyond: exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS,http://dx.doi.org/10.1186/s12977-015-0178-0,PMC4472405,26084487,CC BY,"The restoration of the immune system prompted by antiretroviral therapy (ART) has allowed drastically reducing the mortality and morbidity of HIV infection. However, one main source of clinical concern is the persistence of immune hyperactivation in individuals under ART. Chronically enhanced levels of T-cell activation are associated with several deleterious effects which lead to faster disease progression and slower CD4(+) T-cell recovery during ART. In this article, we discuss the rationale, and review the results, of the use of antimalarial quinolines, such as chloroquine and its derivative hydroxychloroquine, to counteract immune activation in HIV infection. Despite the promising results of several pilot trials, the most recent clinical data indicate that antimalarial quinolines are unlikely to exert a marked beneficial effect on immune activation. Alternative approaches will likely be required to reproducibly decrease immune activation in the setting of HIV infection. If the quinoline-based strategies should nevertheless be pursued in future studies, particular care must be devoted to the dosage selection, in order to maximize the chances to obtain effective in vivo drug concentrations.",2015 Jun 18,"['Savarino, Andrea', 'Shytaj, Iart Luca']",Retrovirology,,,True
1f63075aa219ae29132b49a0c7277632b9b31ba8,PMC,"A survey of UK acute clinicians' knowledge of personal protective requirements for infectious diseases and chemical, biological, and radiological warfare agents",http://dx.doi.org/10.1186/cc14166,PMC4472707,,CC BY,,2015 Mar 16,"['Bond, AR', 'Buckingham, A', 'Schumacher, J']",Crit Care,,,True
802ec789744669d95c380885412457a648a10e0d,PMC,Hepatitis C virus and host cell nuclear transport machinery: a clandestine affair,http://dx.doi.org/10.3389/fmicb.2015.00619,PMC4472997,26150811,CC BY,"There is growing evidence that factors encoded by cytoplasmic replicating viruses functionally interact with components of the nucleocytoplasmic transport apparatus. They do so either to access the cell nucleus, thus affecting genes expression, or to interfere with nuclear transport functionality, hindering host immune response. Recent studies revealed that the hepatitis C virus (HCV) makes no exception, interacting with the host cell nuclear transport machinery at two different levels. On the one hand, small amounts of both core and NS5A localize within the host cell nucleus during productive infection, modulating gene expression and signaling functions to promote persistent infection. On the other hand, HCV infection causes a profound redistribution of certain nucleoproteins to the close proximity of endoplasmic reticulum membrane-derived viral replication factories, where viral RNA amplification occurs. These nucleoporins are believed to form nuclear pore complex-like structures, as suggested by their ability to recruit nuclear localization sequence-bearing proteins. Thus, both processes are linked to virus-induced persistence and pathogenesis, representing possible targets for the development of novel anti-HCV therapeutics.",2015 Jun 19,"['Bonamassa, Barbara', 'Ciccarese, Francesco', 'Antonio, Veronica Di', 'Contarini, Andrea', 'Palù, Giorgio', 'Alvisi, Gualtiero']",Front Microbiol,,,True
d480419719edb5f4d35e01306133b919c1474f89,PMC,BoHV-4-Based Vector Single Heterologous Antigen Delivery Protects STAT1((-/-)) Mice from Monkeypoxvirus Lethal Challenge,http://dx.doi.org/10.1371/journal.pntd.0003850,PMC4473039,26086739,CC BY,"Monkeypox virus (MPXV) is the etiological agent of human (MPX). It is an emerging orthopoxvirus zoonosis in the tropical rain forest of Africa and is endemic in the Congo-basin and sporadic in West Africa; it remains a tropical neglected disease of persons in impoverished rural areas. Interaction of the human population with wildlife increases human infection with MPX virus (MPXV), and infection from human to human is possible. Smallpox vaccination provides good cross-protection against MPX; however, the vaccination campaign ended in Africa in 1980, meaning that a large proportion of the population is currently unprotected against MPXV infection. Disease control hinges on deterring zoonotic exposure to the virus and, barring that, interrupting person-to-person spread. However, there are no FDA-approved therapies against MPX, and current vaccines are limited due to safety concerns. For this reason, new studies on pathogenesis, prophylaxis and therapeutics are still of great interest, not only for the scientific community but also for the governments concerned that MPXV could be used as a bioterror agent. In the present study, a new vaccination strategy approach based on three recombinant bovine herpesvirus 4 (BoHV-4) vectors, each expressing different MPXV glycoproteins, A29L, M1R and B6R were investigated in terms of protection from a lethal MPXV challenge in STAT1 knockout mice. BoHV-4-A-CMV-A29LgD(106)ΔTK, BoHV-4-A-EF1α-M1RgD(106)ΔTK and BoHV-4-A-EF1α-B6RgD(106)ΔTK were successfully constructed by recombineering, and their capacity to express their transgene was demonstrated. A small challenge study was performed, and all three recombinant BoHV-4 appeared safe (no weight-loss or obvious adverse events) following intraperitoneal administration. Further, BoHV-4-A-EF1α-M1RgD(106)ΔTK alone or in combination with BoHV-4-A-CMV-A29LgD(106)ΔTK and BoHV-4-A-EF1α-B6RgD(106)ΔTK, was shown to be able to protect, 100% alone and 80% in combination, STAT1((-/-)) mice against mortality and morbidity. This work demonstrated the efficacy of BoHV-4 based vectors and the use of BoHV-4 as a vaccine-vector platform.",2015 Jun 18,"['Franceschi, Valentina', 'Parker, Scott', 'Jacca, Sarah', 'Crump, Ryan W.', 'Doronin, Konstantin', 'Hembrador, Edguardo', 'Pompilio, Daniela', 'Tebaldi, Giulia', 'Estep, Ryan D.', 'Wong, Scott W.', 'Buller, Mark R.', 'Donofrio, Gaetano']",PLoS Negl Trop Dis,,,True
d44ccd4da37549d25e916096ebd616c982af0422,PMC,In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses,http://dx.doi.org/10.1038/srep11434,PMC4473683,26091504,CC BY,"Newly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population. Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial importance for restricting virus transmission and developing appropriate therapeutic and prophylactic strategies including effective vaccines. Often, the pandemic potential of newly emerging IAV is only fully recognized once the virus starts to spread efficiently causing serious disease in humans. Here, we used a novel phylogenetic algorithm based on the informational spectrum method (ISM) to identify potential CPIV by predicting mutations in the viral hemagglutinin (HA) gene that are likely to (differentially) affect critical interactions between the HA protein and target cells from bird and human origin, respectively. Predictions were subsequently validated by generating pseudotyped retrovirus particles and genetically engineered IAV containing these mutations and characterizing potential effects on virus entry and replication in cells expressing human and avian IAV receptors, respectively. Our data suggest that the ISM-based algorithm is suitable to identify CPIV among IAV strains that are circulating in animal hosts and thus may be a new tool for assessing pandemic risks associated with specific strains.",2015 Jun 19,"['Schmier, Sonja', 'Mostafa, Ahmed', 'Haarmann, Thomas', 'Bannert, Norbert', 'Ziebuhr, John', 'Veljkovic, Veljko', 'Dietrich, Ursula', 'Pleschka, Stephan']",Sci Rep,,,True
16853d835bfed5ec948486100159cebdc5435477,PMC,In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses,http://dx.doi.org/10.1038/srep11434,PMC4473683,26091504,CC BY,"Newly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population. Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial importance for restricting virus transmission and developing appropriate therapeutic and prophylactic strategies including effective vaccines. Often, the pandemic potential of newly emerging IAV is only fully recognized once the virus starts to spread efficiently causing serious disease in humans. Here, we used a novel phylogenetic algorithm based on the informational spectrum method (ISM) to identify potential CPIV by predicting mutations in the viral hemagglutinin (HA) gene that are likely to (differentially) affect critical interactions between the HA protein and target cells from bird and human origin, respectively. Predictions were subsequently validated by generating pseudotyped retrovirus particles and genetically engineered IAV containing these mutations and characterizing potential effects on virus entry and replication in cells expressing human and avian IAV receptors, respectively. Our data suggest that the ISM-based algorithm is suitable to identify CPIV among IAV strains that are circulating in animal hosts and thus may be a new tool for assessing pandemic risks associated with specific strains.",2015 Jun 19,"['Schmier, Sonja', 'Mostafa, Ahmed', 'Haarmann, Thomas', 'Bannert, Norbert', 'Ziebuhr, John', 'Veljkovic, Veljko', 'Dietrich, Ursula', 'Pleschka, Stephan']",Sci Rep,,,False
5f88f46f2e2fe48b05a5cfefcfbe74f4bc90f574,PMC,Malaria and the mobile and migrant population in Cambodia: a population movement framework to inform strategies for malaria control and elimination,http://dx.doi.org/10.1186/s12936-015-0773-5,PMC4474346,26088924,CC BY,"BACKGROUND: The relationships between human population movement (HPM) and health are a concern at global level. In the case of malaria, those links are crucial in relation to the spread of drug resistant parasites and to the elimination of malaria in the Greater Mekong sub-Region (GMS) and beyond. The mobile and migrant populations (MMP) who are involved in forest related activities are both at high risk of being infected with malaria and at risk of receiving late and sub-standard treatment due to poor access to health services. In Cambodia, in 2012, the National Malaria Control Programme (NMCP) identified, as a key objective, the development of a specific strategy for MMPs in order to address these challenges. A population movement framework (PMF) for malaria was developed and operationalized in order to contribute to this strategy. METHODS: A review of the published and unpublished literature was conducted. Based on a synthesis of the results, information was presented and discussed with experienced researchers and programme managers in the Cambodian NMCP and led to the development and refinement of a PMF for malaria. The framework was “tested” for face and content validity with national experts through a workshop approach. RESULTS: In the literature, HPM has been described using various spatial and temporal dimensions both in the context of the spread of anti-malarial drug resistance, and in the context of malaria elimination and previous classifications have categorized MMPs in Cambodia and the GMS through using a number of different criteria. Building on these previous models, the PMF was developed and then refined and populated with in-depth information relevant to Cambodia collected from social science research and field experiences in Cambodia. The framework comprises of the PMF itself, MMP activity profiles and a Malaria Risk Index which is a summation of three related indices: a vulnerability index, an exposure index and an access index which allow a qualitative ranking of malaria risk in the MMP population. Application of currently available data to the framework illustrates that the highest risk population are those highly mobile populations engaged in forest work. CONCLUSION: This paper describes the process of defining MMPs in Cambodia, identifying the different activities and related risks to appropriately target and tailor interventions to the highest risk groups. The framework has been used to develop more targeted behaviour change and outreach interventions for MMPs in Cambodia and its utility and effectiveness will be evaluated as part of those interventions.",2015 Jun 20,"['Guyant, Philippe', 'Canavati, Sara E', 'Chea, Nguon', 'Ly, Po', 'Whittaker, Maxine Anne', 'Roca-Feltrer, Arantxa', 'Yeung, Shunmay']",Malar J,,,True
5d76f48664d2e90c67768d51a2efda3e12c316ce,PMC,Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance,http://dx.doi.org/10.1111/irv.12315,PMC4474494,25912617,CC BY,"The 2009 influenza A(H1N1)pdm09 pandemic highlighted the need for improved scientific knowledge to support better pandemic preparedness and seasonal influenza control. The Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) project, a 5-year (2012–2016) multiagency and multidisciplinary collaboration, aimed to measure disease burden, epidemiology, aetiology, risk factors, immunology, effectiveness of vaccination and other prevention strategies for influenza and other respiratory infectious diseases of public health importance. Two active, prospective, population-based surveillance systems were established for monitoring influenza and other respiratory pathogens among those hospitalized patients with acute respiratory illness and those enrolled patients seeking consultations at sentinel general practices. In 2015, a sero-epidemiological study will use a sample of patients from the same practices. These data will provide a full picture of the disease burden and risk factors from asymptomatic infections to severe hospitalized disease and deaths and related economic burden. The results during the first 2 years (2012–2013) provided scientific evidence to (a) support a change to NZ's vaccination policy for young children due to high influenza hospitalizations in these children; (b) contribute to the revision of the World Health Organization's case definition for severe acute respiratory illness for global influenza surveillance; and (c) contribute in part to vaccine strain selection using vaccine effectiveness assessment in the prevention of influenza-related consultations and hospitalizations. In summary, SHIVERS provides valuable international platforms for supporting seasonal influenza control and pandemic preparedness, and responding to other emerging/endemic respiratory-related infections.",2015 Jul 9,"['Huang, Qiu Sue', 'Turner, Nikki', 'Baker, Michael G', 'Williamson, Deborah A', 'Wong, Conroy', 'Webby, Richard', 'Widdowson, Marc-Alain']",Influenza Other Respir Viruses,,,True
bfbee300d5a290a823a6a06f268e8a02a7e47455,PMC,Clinical differences between respiratory viral and bacterial mono- and dual pathogen detected among Singapore military servicemen with febrile respiratory illness,http://dx.doi.org/10.1111/irv.12312,PMC4474496,25827870,CC BY,"BACKGROUND: Although it is known that febrile respiratory illnesses (FRI) may be caused by multiple respiratory pathogens, there are no population-level studies describing its impact on clinical disease. METHODS: Between May 2009 and October 2012, 7733 FRI patients and controls in the Singapore military had clinical data and nasal wash samples collected prospectively and sent for PCR testing. Patients with one pathogen detected (mono-pathogen) were compared with those with two pathogens (dual pathogen) for differences in basic demographics and clinical presentation. RESULTS: In total, 45.8% had one pathogen detected, 20.2% had two pathogens detected, 30.9% had no pathogens detected, and 3.1% had more than two pathogens. Multiple pathogens were associated with recruits, those with asthma and non-smokers. Influenza A (80.0%), influenza B (73.0%) and mycoplasma (70.6%) were most commonly associated with mono-infections, while adenovirus was most commonly associated with dual infections (62.9%). Influenza A paired with S. pneumoniae had higher proportions of chills and rigors than their respective mono-pathogens (P = 0.03, P = 0.009). H. influenzae paired with either enterovirus or parainfluenzae had higher proportions of cough with phlegm than their respective mono-pathogens. Although there were observed differences in mean proportions of body temperature, nasal symptoms, sore throat, body aches and joint pains between viral and bacterial mono-pathogens, there were few differences between distinct dual-pathogen pairs and their respective mono-pathogen counterparts. CONCLUSION: A substantial number of FRI patients have multiple pathogens detected. Observed clinical differences between patients of dual pathogen and mono-pathogen indicate the likely presence of complex microbial interactions between the various pathogens.",2015 Jul 9,"['Ho, Zheng Jie Marc', 'Zhao, Xiahong', 'Cook, Alex R', 'Loh, Jin Phang', 'Ng, Sock Hoon', 'Tan, Boon Huan', 'Lee, Vernon J']",Influenza Other Respir Viruses,,,True
3a6c69f2092011505ba1b80bb57f88732b42789c,PMC,Middle East respiratory syndrome coronavirus (MERS-Cov) screening of exposed healthcare workers in a tertiary care hospital in Saudi Arabia,http://dx.doi.org/10.1186/2047-2994-4-S1-O57,PMC4474819,,CC BY,,2015 Jun 16,"['Alameer, K', 'Abukhzam, B', 'Khan, W', 'El-Saed, A', 'Balkhy, H']",Antimicrob Resist Infect Control,,,False
dd3e3bb5844179f4fc6f507e88369030c9efed74,PMC,Infection prevention and control strategies for the Middle East respiratory syndrome coronavirus and outcome in Oman,http://dx.doi.org/10.1186/2047-2994-4-S1-O58,PMC4474925,,CC BY,,2015 Jun 16,"['Al Harthy, KSA', 'Al Maani, A', 'Elsheikh, M']",Antimicrob Resist Infect Control,,,False
918a69132dead88bca9d30666a4eb1d3834206a6,PMC,"Current knowledge, attitude and behaviour of hand and food hygiene in a developed residential community of Singapore: a cross-sectional survey",http://dx.doi.org/10.1186/s12889-015-1910-3,PMC4475322,26093582,CC BY,"BACKGROUND: Diarrhoea incidence has been increasing progressively over the past years in developed countries, including Singapore, despite the accessibility and availability to clean water, well-established sanitation infrastructures and regular hygiene promotion. The aim of this study is to determine the current knowledge, attitude and behaviour of hand and food hygiene, and the potential risk factors of diarrhoea in a residential community of Singapore. METHODS: A cross-sectional study was conducted within a residential area in the west of Singapore from June to August 2013. A total of 1,156 household units were randomly sampled and invited to participate in an interviewer-assisted survey using standardised questionnaires. Descriptive, univariate and multivariate analyses were performed using descriptive statistics, Fisher’s Exact test and multivariate logistic regression modelling, respectively. R program was used for all statistical analysis. All tests were conducted at 5 % level of significance with 95 % confidence intervals (CI) reported where applicable. RESULTS: A total of 240 units (20.8 %) consented and responded to the survey invitation. About 77 % of the expected knowledge and attitude were observed in at least 80 % of the participants, compared to only about 31 % of the expected behaviours and practises. Being single [adjusted odds ratio (AOR) = 2.29; 95 % CI = 1.16-4.48], having flu in the past six month (AOR = 3.24; 95 % CI = 1.74-6.06), preferred self-medication (AOR = 2.07; 95 % CI = 1.06–4.12) were risk factors of diarrhoea. Washing hands with water before attending to children or sick persons (AOR = 0.30; 95 % CI = 0.11–0.82), washing hands with water (AOR = 0.16; 95 % CI = 0.05–0.45) and water with soap (AOR = 0.29; 95 % CI = 0.12–0.72) after attending to children or sick persons, and hand washing between 30 s to a minute (AOR = 0.44; 95 % CI = 0.20-0.90) were protective factors against diarrhoea. CONCLUSIONS: Good knowledge and attitude of the participants did not positively translate into high compliance and motivation to perform good hygiene practices. This observation may have resulted in a significant extent on the increasing diarrhoea incidences. Current interventions may be improved with more active community partnership among the residents, schools and the relevant social organizations, to raise awareness on the importance of compliance to good hygiene practices, and the risk factors of diarrhoea. A large case–control study would be required to validate these findings in future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1910-3) contains supplementary material, which is available to authorized users.",2015 Jun 21,"['Pang, Junxiong', 'Chua, Shao Wei Jonathan Lumen', 'Hsu, Liyang']",BMC Public Health,,,True
6d86f444589890a4657acab7888a38806287387e,PMC,Characterization of the bacterial gut microbiota of piglets suffering from new neonatal porcine diarrhoea,http://dx.doi.org/10.1186/s12917-015-0419-4,PMC4476181,26099928,CC BY,"BACKGROUND: In recent years, new neonatal porcine diarrhoea (NNPD) of unknown aetiology has emerged in Denmark. NNPD affects piglets during the first week of life and results in impaired welfare, decreased weight gain, and in the worst-case scenario death. Commonly used preventative interventions such as vaccination or treatment with antibiotics, have a limited effect on NNPD. Previous studies have investigated the clinical manifestations, histopathology, and to some extent, microbiological findings; however, these studies were either inconclusive or suggested that Enterococci, possibly in interaction with Escherichia coli, contribute to the aetiology of NNPD. This study examined ileal and colonic luminal contents of 50 control piglets and 52 NNPD piglets by means of the qPCR-based Gut Microbiotassay and 16 samples by 454 sequencing to study the composition of the bacterial gut microbiota in relation to NNPD. RESULTS: NNPD was associated with a diminished quantity of bacteria from the phyla Actinobacteria and Firmicutes while genus Enterococcus was more than 24 times more abundant in diarrhoeic piglets. The number of bacteria from the phylum Fusobacteria was also doubled in piglets suffering from diarrhoea. With increasing age, the gut microbiota of NNPD affected piglet and control piglets became more diverse. Independent of diarrhoeic status, piglets from first parity sows (gilts) possessed significantly more bacteria from family Enterobacteriaceae and species E. coli, and fewer bacteria from phylum Firmicutes. Piglets born to gilts had 25 times higher odds of having NNPD compared with piglets born to multiparous sows. Finally, the co-occurrence of genus Enterococcus and species E. coli contributed to the risk of having NNPD. CONCLUSION: The results of this study support previous findings that points towards genus Enterococcus and species E. coli to be involved in the pathogenesis of NNPD. Moreover, the results indicate that NNPD is associated with a disturbed bacterial composition and larger variation between the diarrhoeic piglets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0419-4) contains supplementary material, which is available to authorized users.",2015 Jun 23,"['Hermann-Bank, Marie Louise', 'Skovgaard, Kerstin', 'Stockmarr, Anders', 'Strube, Mikael Lenz', 'Larsen, Niels', 'Kongsted, Hanne', 'Ingerslev, Hans-Christian', 'Mølbak, Lars', 'Boye, Mette']",BMC Vet Res,,,True
82d76d619e7be4f0ef2490f933d140ec9f722a55,PMC,Genetic drift of human coronavirus OC43 spike gene during adaptive evolution,http://dx.doi.org/10.1038/srep11451,PMC4476415,26099036,CC BY,"Coronaviruses (CoVs) continuously threaten human health. However, to date, the evolutionary mechanisms that govern CoV strain persistence in human populations have not been fully understood. In this study, we characterized the evolution of the major antigen-spike (S) gene in the most prevalent human coronavirus (HCoV) OC43 using phylogenetic and phylodynamic analysis. Among the five known HCoV-OC43 genotypes (A to E), higher substitution rates and dN/dS values as well as more positive selection sites were detected in the S gene of genotype D, corresponding to the most dominant HCoV epidemic in recent years. Further analysis showed that the majority of substitutions were located in the S1 subunit. Among them, seven positive selection sites were chronologically traced in the temporal evolution routes of genotype D, and six were located around the critical sugar binding region in the N-terminal domain (NTD) of S protein, an important sugar binding domain of CoV. These findings suggest that the genetic drift of the S gene may play an important role in genotype persistence in human populations, providing insights into the mechanisms of HCoV-OC43 adaptive evolution.",2015 Jun 22,"['Ren, Lili', 'Zhang, Yue', 'Li, Jianguo', 'Xiao, Yan', 'Zhang, Jing', 'Wang, Ying', 'Chen, Lan', 'Paranhos-Baccalà, Gláucia', 'Wang, Jianwei']",Sci Rep,,,True
fdc71cdcdfa62100451d8dde47fc4d04a6f3c7f9,PMC,Genetic drift of human coronavirus OC43 spike gene during adaptive evolution,http://dx.doi.org/10.1038/srep11451,PMC4476415,26099036,CC BY,"Coronaviruses (CoVs) continuously threaten human health. However, to date, the evolutionary mechanisms that govern CoV strain persistence in human populations have not been fully understood. In this study, we characterized the evolution of the major antigen-spike (S) gene in the most prevalent human coronavirus (HCoV) OC43 using phylogenetic and phylodynamic analysis. Among the five known HCoV-OC43 genotypes (A to E), higher substitution rates and dN/dS values as well as more positive selection sites were detected in the S gene of genotype D, corresponding to the most dominant HCoV epidemic in recent years. Further analysis showed that the majority of substitutions were located in the S1 subunit. Among them, seven positive selection sites were chronologically traced in the temporal evolution routes of genotype D, and six were located around the critical sugar binding region in the N-terminal domain (NTD) of S protein, an important sugar binding domain of CoV. These findings suggest that the genetic drift of the S gene may play an important role in genotype persistence in human populations, providing insights into the mechanisms of HCoV-OC43 adaptive evolution.",2015 Jun 22,"['Ren, Lili', 'Zhang, Yue', 'Li, Jianguo', 'Xiao, Yan', 'Zhang, Jing', 'Wang, Ying', 'Chen, Lan', 'Paranhos-Baccalà, Gláucia', 'Wang, Jianwei']",Sci Rep,,,False
1f91af10bd4371cfb8d9e08a8a1518d8bbd6d4f5,PMC,"Host Subtraction, Filtering and Assembly Validations for Novel Viral Discovery Using Next Generation Sequencing Data",http://dx.doi.org/10.1371/journal.pone.0129059,PMC4476701,26098299,CC BY,"The use of next generation sequencing (NGS) to identify novel viral sequences from eukaryotic tissue samples is challenging. Issues can include the low proportion and copy number of viral reads and the high number of contigs (post-assembly), making subsequent viral analysis difficult. Comparison of assembly algorithms with pre-assembly host-mapping subtraction using a short-read mapping tool, a k-mer frequency based filter and a low complexity filter, has been validated for viral discovery with Illumina data derived from naturally infected liver tissue and simulated data. Assembled contig numbers were significantly reduced (up to 99.97%) by the application of these pre-assembly filtering methods. This approach provides a validated method for maximizing viral contig size as well as reducing the total number of assembled contigs that require down-stream analysis as putative viral nucleic acids.",2015 Jun 22,"['Daly, Gordon M.', 'Leggett, Richard M.', 'Rowe, William', 'Stubbs, Samuel', 'Wilkinson, Maxim', 'Ramirez-Gonzalez, Ricardo H.', 'Caccamo, Mario', 'Bernal, William', 'Heeney, Jonathan L.']",PLoS One,,,True
cf085fe7f16317b15dddc417b76252025fc80f61,PMC,Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis,http://dx.doi.org/10.1038/ncomms8375,PMC4477037,26077231,CC BY,"Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF activity using an in vitro bioassay, depending on the experimental conditions, while, when injected in mice together with human GM-CSF, they lead to the accumulation of a large pool of circulating GM-CSF that remains partially bioavailable. In contrast, a combination of three non-cross-competing antibodies completely neutralizes GM-CSF activity in vitro by sequestering the cytokine in high-molecular-weight complexes, and in vivo promotes the rapid degradation of GM-CSF-containing immune complexes in an Fc-dependent manner. Taken together, these findings provide a plausible explanation for the severe phenotype of PAP patients and for the safety of treatments based on single anti-GM-CSF monoclonal antibodies.",2015 Jun 16,"['Piccoli, Luca', 'Campo, Ilaria', 'Fregni, Chiara Silacci', 'Rodriguez, Blanca Maria Fernandez', 'Minola, Andrea', 'Sallusto, Federica', 'Luisetti, Maurizio', 'Corti, Davide', 'Lanzavecchia, Antonio']",Nat Commun,,,True
288f6a1df837cdc3cb81ed98a89f6c893ffe0b13,PMC,Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis,http://dx.doi.org/10.1038/ncomms8375,PMC4477037,26077231,CC BY,"Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF activity using an in vitro bioassay, depending on the experimental conditions, while, when injected in mice together with human GM-CSF, they lead to the accumulation of a large pool of circulating GM-CSF that remains partially bioavailable. In contrast, a combination of three non-cross-competing antibodies completely neutralizes GM-CSF activity in vitro by sequestering the cytokine in high-molecular-weight complexes, and in vivo promotes the rapid degradation of GM-CSF-containing immune complexes in an Fc-dependent manner. Taken together, these findings provide a plausible explanation for the severe phenotype of PAP patients and for the safety of treatments based on single anti-GM-CSF monoclonal antibodies.",2015 Jun 16,"['Piccoli, Luca', 'Campo, Ilaria', 'Fregni, Chiara Silacci', 'Rodriguez, Blanca Maria Fernandez', 'Minola, Andrea', 'Sallusto, Federica', 'Luisetti, Maurizio', 'Corti, Davide', 'Lanzavecchia, Antonio']",Nat Commun,,,False
c831071c9229a681189522e08cfc3b64f84f95db,PMC,Ionizing air affects influenza virus infectivity and prevents airborne-transmission,http://dx.doi.org/10.1038/srep11431,PMC4477231,26101102,CC BY,"By the use of a modified ionizer device we describe effective prevention of airborne transmitted influenza A (strain Panama 99) virus infection between animals and inactivation of virus (>97%). Active ionizer prevented 100% (4/4) of guinea pigs from infection. Moreover, the device effectively captured airborne transmitted calicivirus, rotavirus and influenza virus, with recovery rates up to 21% after 40 min in a 19 m(3) room. The ionizer generates negative ions, rendering airborne particles/aerosol droplets negatively charged and electrostatically attracts them to a positively charged collector plate. Trapped viruses are then identified by reverse transcription quantitative real-time PCR. The device enables unique possibilities for rapid and simple removal of virus from air and offers possibilities to simultaneously identify and prevent airborne transmission of viruses.",2015 Jun 23,"['Hagbom, Marie', 'Nordgren, Johan', 'Nybom, Rolf', 'Hedlund, Kjell-Olof', 'Wigzell, Hans', 'Svensson, Lennart']",Sci Rep,,,True
ed461df407adc47368723e0d97af0d21630e6dde,PMC,N-terminal functional domain of Gasdermin A3 regulates mitochondrial homeostasis via mitochondrial targeting,http://dx.doi.org/10.1186/s12929-015-0152-0,PMC4477613,26100518,CC BY,"BACKGROUND: The epidermis forms a critical barrier that is maintained by orchestrated programs of proliferation, differentiation, and cell death. Gene mutations that disturb this turnover process may cause skin diseases. Human GASDERMIN A (GSDMA) is frequently silenced in gastric cancer cell lines and its overexpression has been reported to induce apoptosis. GSDMA has also been linked with airway hyperresponsiveness in genetic association studies. The function of GSDMA in the skin was deduced by dominant mutations in mouse gasdermin A3 (Gsdma3), which caused skin inflammation and hair loss. However, the mechanism for the autosomal dominance of Gsdma3 mutations and the mode of Gsdma3’s action remain unanswered. RESULTS: We demonstrated a novel function of Gsdma3 in modulating mitochondrial oxidative stress. We showed that Gsdma3 is regulated by intramolecular fold-back inhibition, which is disrupted by dominant mutations in the C-terminal domain. The unmasked N-terminal domain of Gsdma3 associates with Hsp90 and is delivered to mitochondrial via mitochondrial importer receptor Tom70, where it interacts with the mitochondrial chaperone Trap1 and causes increased production of mitochondrial reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and mitochondrial permeability transition (MPT). Overexpression of the C-terminal domain of Gsdma3 as well as pharmacological interventions of mitochondrial translocation, ROS production, and MPT pore opening alleviate the cell death induced by Gsdma3 mutants. CONCLUSIONS: Our results indicate that the genetic mutations in the C-terminal domain of Gsdma3 are gain-of-function mutations which unmask the N-terminal functional domain of Gsdma3. Gsdma3 regulates mitochondrial oxidative stress through mitochondrial targeting. Since mitochondrial ROS has been shown to promote epidermal differentiation, we hypothesize that Gsdma3 regulates context-dependent response of keratinocytes to differentiation and cell death signals by impinging on mitochondria. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-015-0152-0) contains supplementary material, which is available to authorized users.",2015 Jun 24,"['Lin, Pei-Hsuan', 'Lin, Hsien-Yi', 'Kuo, Cheng-Chin', 'Yang, Liang-Tung']",J Biomed Sci,,,False
4565dc1b4397e2959bd9e41cf1b32c37a836f7e9,PMC,N-terminal functional domain of Gasdermin A3 regulates mitochondrial homeostasis via mitochondrial targeting,http://dx.doi.org/10.1186/s12929-015-0152-0,PMC4477613,26100518,CC BY,"BACKGROUND: The epidermis forms a critical barrier that is maintained by orchestrated programs of proliferation, differentiation, and cell death. Gene mutations that disturb this turnover process may cause skin diseases. Human GASDERMIN A (GSDMA) is frequently silenced in gastric cancer cell lines and its overexpression has been reported to induce apoptosis. GSDMA has also been linked with airway hyperresponsiveness in genetic association studies. The function of GSDMA in the skin was deduced by dominant mutations in mouse gasdermin A3 (Gsdma3), which caused skin inflammation and hair loss. However, the mechanism for the autosomal dominance of Gsdma3 mutations and the mode of Gsdma3’s action remain unanswered. RESULTS: We demonstrated a novel function of Gsdma3 in modulating mitochondrial oxidative stress. We showed that Gsdma3 is regulated by intramolecular fold-back inhibition, which is disrupted by dominant mutations in the C-terminal domain. The unmasked N-terminal domain of Gsdma3 associates with Hsp90 and is delivered to mitochondrial via mitochondrial importer receptor Tom70, where it interacts with the mitochondrial chaperone Trap1 and causes increased production of mitochondrial reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and mitochondrial permeability transition (MPT). Overexpression of the C-terminal domain of Gsdma3 as well as pharmacological interventions of mitochondrial translocation, ROS production, and MPT pore opening alleviate the cell death induced by Gsdma3 mutants. CONCLUSIONS: Our results indicate that the genetic mutations in the C-terminal domain of Gsdma3 are gain-of-function mutations which unmask the N-terminal functional domain of Gsdma3. Gsdma3 regulates mitochondrial oxidative stress through mitochondrial targeting. Since mitochondrial ROS has been shown to promote epidermal differentiation, we hypothesize that Gsdma3 regulates context-dependent response of keratinocytes to differentiation and cell death signals by impinging on mitochondria. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-015-0152-0) contains supplementary material, which is available to authorized users.",2015 Jun 24,"['Lin, Pei-Hsuan', 'Lin, Hsien-Yi', 'Kuo, Cheng-Chin', 'Yang, Liang-Tung']",J Biomed Sci,,,False
5f658c058c7877ad7df3f02da1ee3593b60e4429,PMC,N-terminal functional domain of Gasdermin A3 regulates mitochondrial homeostasis via mitochondrial targeting,http://dx.doi.org/10.1186/s12929-015-0152-0,PMC4477613,26100518,CC BY,"BACKGROUND: The epidermis forms a critical barrier that is maintained by orchestrated programs of proliferation, differentiation, and cell death. Gene mutations that disturb this turnover process may cause skin diseases. Human GASDERMIN A (GSDMA) is frequently silenced in gastric cancer cell lines and its overexpression has been reported to induce apoptosis. GSDMA has also been linked with airway hyperresponsiveness in genetic association studies. The function of GSDMA in the skin was deduced by dominant mutations in mouse gasdermin A3 (Gsdma3), which caused skin inflammation and hair loss. However, the mechanism for the autosomal dominance of Gsdma3 mutations and the mode of Gsdma3’s action remain unanswered. RESULTS: We demonstrated a novel function of Gsdma3 in modulating mitochondrial oxidative stress. We showed that Gsdma3 is regulated by intramolecular fold-back inhibition, which is disrupted by dominant mutations in the C-terminal domain. The unmasked N-terminal domain of Gsdma3 associates with Hsp90 and is delivered to mitochondrial via mitochondrial importer receptor Tom70, where it interacts with the mitochondrial chaperone Trap1 and causes increased production of mitochondrial reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and mitochondrial permeability transition (MPT). Overexpression of the C-terminal domain of Gsdma3 as well as pharmacological interventions of mitochondrial translocation, ROS production, and MPT pore opening alleviate the cell death induced by Gsdma3 mutants. CONCLUSIONS: Our results indicate that the genetic mutations in the C-terminal domain of Gsdma3 are gain-of-function mutations which unmask the N-terminal functional domain of Gsdma3. Gsdma3 regulates mitochondrial oxidative stress through mitochondrial targeting. Since mitochondrial ROS has been shown to promote epidermal differentiation, we hypothesize that Gsdma3 regulates context-dependent response of keratinocytes to differentiation and cell death signals by impinging on mitochondria. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-015-0152-0) contains supplementary material, which is available to authorized users.",2015 Jun 24,"['Lin, Pei-Hsuan', 'Lin, Hsien-Yi', 'Kuo, Cheng-Chin', 'Yang, Liang-Tung']",J Biomed Sci,,,False
ffd291065f3e320c4d8417a78d61116f3a919fae,PMC,N-terminal functional domain of Gasdermin A3 regulates mitochondrial homeostasis via mitochondrial targeting,http://dx.doi.org/10.1186/s12929-015-0152-0,PMC4477613,26100518,CC BY,"BACKGROUND: The epidermis forms a critical barrier that is maintained by orchestrated programs of proliferation, differentiation, and cell death. Gene mutations that disturb this turnover process may cause skin diseases. Human GASDERMIN A (GSDMA) is frequently silenced in gastric cancer cell lines and its overexpression has been reported to induce apoptosis. GSDMA has also been linked with airway hyperresponsiveness in genetic association studies. The function of GSDMA in the skin was deduced by dominant mutations in mouse gasdermin A3 (Gsdma3), which caused skin inflammation and hair loss. However, the mechanism for the autosomal dominance of Gsdma3 mutations and the mode of Gsdma3’s action remain unanswered. RESULTS: We demonstrated a novel function of Gsdma3 in modulating mitochondrial oxidative stress. We showed that Gsdma3 is regulated by intramolecular fold-back inhibition, which is disrupted by dominant mutations in the C-terminal domain. The unmasked N-terminal domain of Gsdma3 associates with Hsp90 and is delivered to mitochondrial via mitochondrial importer receptor Tom70, where it interacts with the mitochondrial chaperone Trap1 and causes increased production of mitochondrial reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and mitochondrial permeability transition (MPT). Overexpression of the C-terminal domain of Gsdma3 as well as pharmacological interventions of mitochondrial translocation, ROS production, and MPT pore opening alleviate the cell death induced by Gsdma3 mutants. CONCLUSIONS: Our results indicate that the genetic mutations in the C-terminal domain of Gsdma3 are gain-of-function mutations which unmask the N-terminal functional domain of Gsdma3. Gsdma3 regulates mitochondrial oxidative stress through mitochondrial targeting. Since mitochondrial ROS has been shown to promote epidermal differentiation, we hypothesize that Gsdma3 regulates context-dependent response of keratinocytes to differentiation and cell death signals by impinging on mitochondria. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-015-0152-0) contains supplementary material, which is available to authorized users.",2015 Jun 24,"['Lin, Pei-Hsuan', 'Lin, Hsien-Yi', 'Kuo, Cheng-Chin', 'Yang, Liang-Tung']",J Biomed Sci,,,False
32d5699f514f8d58fa7939fefaea6ef9fce1121c,PMC,N-terminal functional domain of Gasdermin A3 regulates mitochondrial homeostasis via mitochondrial targeting,http://dx.doi.org/10.1186/s12929-015-0152-0,PMC4477613,26100518,CC BY,"BACKGROUND: The epidermis forms a critical barrier that is maintained by orchestrated programs of proliferation, differentiation, and cell death. Gene mutations that disturb this turnover process may cause skin diseases. Human GASDERMIN A (GSDMA) is frequently silenced in gastric cancer cell lines and its overexpression has been reported to induce apoptosis. GSDMA has also been linked with airway hyperresponsiveness in genetic association studies. The function of GSDMA in the skin was deduced by dominant mutations in mouse gasdermin A3 (Gsdma3), which caused skin inflammation and hair loss. However, the mechanism for the autosomal dominance of Gsdma3 mutations and the mode of Gsdma3’s action remain unanswered. RESULTS: We demonstrated a novel function of Gsdma3 in modulating mitochondrial oxidative stress. We showed that Gsdma3 is regulated by intramolecular fold-back inhibition, which is disrupted by dominant mutations in the C-terminal domain. The unmasked N-terminal domain of Gsdma3 associates with Hsp90 and is delivered to mitochondrial via mitochondrial importer receptor Tom70, where it interacts with the mitochondrial chaperone Trap1 and causes increased production of mitochondrial reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and mitochondrial permeability transition (MPT). Overexpression of the C-terminal domain of Gsdma3 as well as pharmacological interventions of mitochondrial translocation, ROS production, and MPT pore opening alleviate the cell death induced by Gsdma3 mutants. CONCLUSIONS: Our results indicate that the genetic mutations in the C-terminal domain of Gsdma3 are gain-of-function mutations which unmask the N-terminal functional domain of Gsdma3. Gsdma3 regulates mitochondrial oxidative stress through mitochondrial targeting. Since mitochondrial ROS has been shown to promote epidermal differentiation, we hypothesize that Gsdma3 regulates context-dependent response of keratinocytes to differentiation and cell death signals by impinging on mitochondria. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-015-0152-0) contains supplementary material, which is available to authorized users.",2015 Jun 24,"['Lin, Pei-Hsuan', 'Lin, Hsien-Yi', 'Kuo, Cheng-Chin', 'Yang, Liang-Tung']",J Biomed Sci,,,True
b3ad716630b356b1399e9df08cad73b1e92f317d,PMC,"Changing risk awareness and personal protection measures for low to high pathogenic avian influenza in live-poultry markets in Taiwan, 2007 to 2012",http://dx.doi.org/10.1186/s12879-015-0987-8,PMC4478710,26104109,CC BY,"BACKGROUND: Outbreaks of low and high pathogenic avian influenza (LPAI, HPAI) H5N2 in chickens have occurred in Taiwan since 2003 and 2012, respectively. Fully understanding the different awareness, attitudes and protective behaviors adopted by workers in live-poultry markets (LPMWs) and local community residents (CRs) to face the challenges of LPAI and HPAI is very important to minimize viral adaptations to human populations. METHODS: A structural questionnaire containing information on respondents’ occupation, personal risk awareness, attitudes toward different policies, and preventative measures was administered. The two-stage survey (before and after HPAI H5N2 outbreaks) was conducted from 2007 to 2012, including: (1) 430 LPMWs and 418 CRs at LPMs from different geographical areas of Taiwan after the government announced outbreaks of LPAI H5N2 during 2007–2009, and (2) 73 LPMWs and 152 CRs at two LPMs in central Taiwan after the HPAI H5N2 outbreaks in 2012. The chi-squared test and logistic regression were applied for univariate and multivariate analyses, respectively. RESULTS: Before HPAI-H5N2 outbreaks, higher educated respondents demonstrated greater risk awareness and concerns regarding AI. However, LPM-workers protected themselves less from AI viruses (AIVs) and had lower acceptance of human or avian influenza vaccines. Most importantly, the participants who opposed (versus agreed with) the policy on banning live-poultry slaughtering at LPMs reported lower awareness of government prevention and control policies [Odds Ratio (OR): 0.76, 95 % Confidence Interval (CI): 0.56–1.01] or practiced preventive measures (OR: 0.42, 95 % CI: 0.25–0.70). After HPAI-H5N2 outbreaks, the risk awareness about AI in central Taiwan significantly increased [LPAI to HPAI LPMWs: 34.6 to 65.6 %, p < 0.05; CRs: 44.0 to 76.5 %, p < 0.05] and LPMWs’ belief in the effectiveness of vaccination to prevent human or avian influenza virus infection strikingly decreased (92.3 to 68.5 %, p < 0.05). CONCLUSIONS: Risk awareness depends on high or low pathogenicity of AIVs, working in LPMs, levels of education, age, and proximity to the sites of severe AI outbreaks. Regardless of novel LPAI or HPAI virus reassortants that pose public health risks, prompt and clear risk communication focusing on both correct information about AIVs and the most appropriate preventive measures are important for effective prevention of human infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0987-8) contains supplementary material, which is available to authorized users.",2015 Jun 24,"['Liu, Ming-Der', 'Chan, Ta-Chien', 'Wan, Cho-Hua', 'Lin, Hsiu-Ping', 'Tung, Tsung-Hua', 'Hu, Fu-Chang', 'King, Chwan-Chuen']",BMC Infect Dis,,,True
933e9eb0d544bb5afe34f6d6049b4c8bc5e96d19,PMC,"Prevalence of respiratory virus in symptomatic children in private physician office settings in five communities of the state of Veracruz, Mexico",http://dx.doi.org/10.1186/s13104-015-1239-0,PMC4479372,26108920,CC BY,"BACKGROUND: Acute respiratory tract infections are the leading cause of morbidity and mortality in children worldwide. Many studies have described the frequency of viruses in hospitalized patients, but studies describing the prevalence of viruses in the community setting are limited, particularly in developing countries, where most of the deaths from serious respiratory diseases occur. The aim of this study was to evaluate the diversity of respiratory viruses in the community setting using molecular diagnostic tools, as well as the clinical characteristics of respiratory viral infections in the general pediatric practice in Mexico. METHODS: Children with respiratory tract infections attending private pediatric practices during a 10-month period in five cities of the state of Veracruz were included. Nasal swabs were taken and processed by a multiplex detection kit for 15 respiratory viruses. RESULTS: 525 children were included from July 2011 to May 2012; 44% were female, mean age was 45 months. The 3 most frequent clinical diagnosis were: rhinopharyngitis 68%, pharyngitis 18%, and 3.3% influenza-like illness. 71.5% of the samples were positive for virus. The five most frequent pathogens were respiratory syncycitial virus in 18.3% of the children, rhinovirus in 17.5%, influenza A 9.1%, adenovirus 7.2%, and enterovirus 3.4%, although all 15 viruses were detected; there were viral coinfections in 14.1%, and 28.5% of the samples were negative. CONCLUSIONS: A large proportion of respiratory infections in the community setting in Mexico was associated to viruses. Although testing for common respiratory pathogens in children with acute respiratory tract infections may lead to a better understanding of the role of viral pathogens in, and eventually to improvement in the management of, individual patients, additional prospective studies are required to study the need of routinely using such tests in general pediatric practices in resource-limited countries.",2015 Jun 25,"['Wong-Chew, Rosa M', 'Espinoza, Marco A', 'Taboada, Blanca', 'Aponte, Fernando E', 'Arias-Ortiz, María A', 'Monge-Martínez, Jesús', 'Rodríguez-Vázquez, Rubén', 'Díaz-Hernández, Fidel', 'Zárate-Vidal, Fernando', 'Santos-Preciado, José I', 'López, Susana', 'Arias, Carlos F']",BMC Res Notes,,,True
44d9ad484dc917e82daa41c802c2157d3f20dda4,PMC,Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination,http://dx.doi.org/10.1186/s13578-015-0025-y,PMC4480891,26113972,CC BY,"BACKGROUND: DNA vaccines have emerged as attractive candidates for the control of human papillomavirus (HPV)-associated malignancies. However, DNA vaccines suffer from limited immunogenicity and thus strategies to enhance DNA vaccine potency are needed. We have previously demonstrated that for DNA vaccines encoding HPV-16 E7 antigen (CRT/E7) linkage with calreticulin (CRT) linked enhances both the E7-specific CD8(+) T cell immune responses and antitumor effects against E7-expressing tumors. In the current study, we aim to introduce an approach to elicit potent CD4(+) T cell help for the enhancement of antigen-specific CD8(+) T cell immune responses generated by CRT/E7 DNA vaccination by using co-administration of a DNA vector expressing papillomavirus major and minor capsid antigens, L1 and L2. RESULT: We showed that co-administration of vectors containing codon-optimized bovine papillomavirus type 1 (BPV-1) L1 and L2 in combination with DNA vaccines could elicit enhanced antigen-specific CD8(+) in both CRT/E7 and ovalbumin (OVA) antigenic systems. We also demonstrated that co-administration of vectors expressing BPV-1 L1 and/or L2 DNA with CRT/E7 DNA led to the generation of L1/L2-specific CD4(+) T cell immune responses and L1-specific neutralizing antibodies. Furthermore, we showed that co-administration with DNA encoding BPV1 L1 significantly enhances the therapeutic antitumor effects generated by CRT/E7 DNA vaccination. In addition, the observed enhancement of CD8(+) T cell immune responses by DNA encoding L1 and L2 was also found to extend to HPV-16 L1/L2 system. CONCLUSION: Our strategy elicits both potent neutralizing antibody and therapeutic responses and may potentially be extended to other antigenic systems beyond papillomavirus for the control of infection and/or cancer.",2015 Jun 25,"['Yang, Benjamin', 'Yang, Andrew', 'Peng, Shiwen', 'Pang, Xiaowu', 'Roden, Richard B.S.', 'Wu, T.-C.', 'Hung, Chien-Fu']",Cell Biosci,,,True
00ae0041374cbbf28df0d2cbeb08c1396a4f7878,PMC,Enzyme assays for synthesis and degradation of 2-5As and other 2′-5′ oligonucleotides,http://dx.doi.org/10.1186/s12858-015-0043-8,PMC4481073,26113370,CC BY,"BACKGROUND: The 5′-triphosphorylated, 2′-5′-linked oligoadenylate polyribonucleotides (2-5As) are central to the interferon-induced antiviral 2-5A system. The 2-5As bind and activate the RNase L, an endoRNase degrading viral and cellular RNA leading to inhibition of viral replication. The 2-5A system is tightly controlled by synthesis and degradation of 2-5As. Whereas synthesis is mediated by the 2′-5′ oligoadenylate synthetase family of enzymes, degradation seems to be orchestrated by multiple enzyme nucleases including phosphodiesterase 12, the ectonucleotide pyrophosphatase/phosphodiesterase 1 and the A-kinase anchoring protein 7. RESULTS: Here we present assay tools for identification and characterization of the enzymes regulating cellular 2-5A levels. A procedure is described for the production of 2′-5′ oligoadenylates, which are then used as substrates for development and demonstration of enzyme assays measuring synthetase and nuclease activities, respectively. The synthetase assays produce only a single reaction product allowing for very precise kinetic assessment of the enzymes. We present an assay using dATP and the A(pA)(3) tetramer core as substrates, which requires prior isolation of A(pA)(3). A synthetase assay using either of the dNTPs individually together with NAD(+) as substrates is also presented. The nuclease reactions make use of the isolated 2′-5′ oligoadenylates in producing a mixture of shorter reaction products, which are resolved by ion-exchange chromatography to determine the enzyme activities. A purified human 2′-5′ oligoadenylate synthetase and a purified human phosphodiesterase 12 along with crude extracts expressing those proteins, are used to demonstrate the assays. CONCLUSIONS: This paper comprises an assay toolbox for identification and characterization of the synthetases and nucleases regulating cellular 2-5A levels. Assays are presented for both enzyme families. The assays can also be used to address a broader cellular role of the OAS enzymes, based on the multiple substrate specificity intrinsic to these proteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12858-015-0043-8) contains supplementary material, which is available to authorized users.",2015 Jun 26,"['Poulsen, Jesper Buchhave', 'Kjær, Karina Hansen', 'Justesen, Just', 'Martensen, Pia Møller']",BMC Biochem,,,True
5a575cf8c90efa9e40cfbf87f2a202bb39d68951,PMC,Evaluation of Four Commercial Multiplex Molecular Tests for the Diagnosis of Acute Respiratory Infections,http://dx.doi.org/10.1371/journal.pone.0130378,PMC4481272,26107509,CC BY,"Acute Respiratory Infections (ARIs) are responsible for considerable morbidity and mortality worldwide. Documentation of respiratory specimens can help for an appropriate clinical management with a significant effect on the disease progress in patient, the antimicrobial therapy used and the risk of secondary spread of infection. Here, we compared the performances of four commercial multiplex kits used in French University Hospital diagnostic microbiology laboratories for the detection of ARI pathogens (i.e., the xTAG Respiratory Viral Panel Fast, RespiFinder SMART 22, CLART PneumoVir and Fast Track Diagnostics Respiratory Pathogen 33 kits). We used a standardised nucleic acids extraction protocol and a comprehensive comparative approach that mixed reference to well established real-time PCR detection techniques and analysis of convergent positive results. We tested 166 respiratory clinical samples and identified a global high degree of correlation for at least three of the techniques (xTAG, RespiFinder and FTD33). For these techniques, the highest Youden’s index (YI), positive predictive (PPV) and specificity (Sp) values were observed for Core tests (e.g., influenza A [YI:0.86–1.00; PPV:78.95–100.00; Sp:97.32–100.00] & B [YI:0.44–1.00; PPV:100.00; Sp:100.00], hRSV [YI:0.50–0.99; PPV:85.71–100.00; Sp:99.38–100.00], hMPV [YI:0.71–1.00; PPV:83.33–100.00; Sp:99.37–100.00], EV/hRV [YI:0.62–0.82; PPV:93.33–100.00; Sp:94.48–100.00], AdV [YI:1.00; PPV:100.00; Sp:100.00] and hBoV [YI:0.20–0.80; PPV:57.14–100.00; Sp:98.14–100.00]). The present study completed an overview of the multiplex techniques available for the diagnosis of acute respiratory infections.",2015 Jun 24,"['Salez, Nicolas', 'Vabret, Astrid', 'Leruez-Ville, Marianne', 'Andreoletti, Laurent', 'Carrat, Fabrice', 'Renois, Fanny', 'de Lamballerie, Xavier']",PLoS One,,,True
334adcddbb251335c86c3a5d79a0f66b526109ff,PMC,Complete Genome Sequences of Two Genetically Distinct Variants of Porcine Epidemic Diarrhea Virus in the Eastern Region of Thailand,http://dx.doi.org/10.1128/genomeA.00634-15,PMC4481281,26112783,CC BY,"Porcine epidemic diarrhea virus (PEDV) has continued to cause sporadic outbreaks in Thailand since 2007. Previously, PEDV in Thailand was a new variant containing an insertion and deletion in the spike gene. Herein, full-length genome sequences are reported for two variants of PEDV isolates from pigs displaying diarrhea in Thailand.",2015 Jun 25,"['Cheun-Arom, Thaniwan', 'Temeeyasen, Gun', 'Srijangwad, Anchalee', 'Tripipat, Thitima', 'Sangmalee, Suphattra', 'Vui, Dam Thi', 'Chuanasa, Taksina', 'Tantituvanont, Angkana', 'Nilubol, Dachrit']",Genome Announc,,,True
ccc32d31656760db245b5cd683d144eb013624c3,PMC,Experimental African Trypanosome Infection by Needle Passage or Natural Tsetse Fly Challenge Thwarts the Development of Collagen-Induced Arthritis in DBA/1 Prone Mice via an Impairment of Antigen Specific B Cell Autoantibody Titers,http://dx.doi.org/10.1371/journal.pone.0130431,PMC4482398,26110416,CC BY,"Collagen-induced arthritis is a B cell-mediated autoimmune disease. Recently published studies have demonstrated that in some rare cases pathogens can confer protection from autoimmunity. Trypanosoma brucei parasites are tsetse fly transmitted extracellular protozoans causing sleeping sickness disease in humans and Nagana in livestock in sub-Saharan endemic areas. In the past, we demonstrated that trypanosome infections impair B cell homeostasis and abolish vaccine-induced protection against unrelated antigens. Hence, here we hypothesized that trypanosome infection can affect the onset of CIA by specifically dampening specific B-cell responses and type II collagen antibody titers in DBA/1 prone mice. We observed a substantial delay in the onset of collagen-induced arthritis in T. brucei-infected DBA/1 mice that correlates with a drastic decrease of type II collagen titers of the different IgG isotypes in the serum. Treatment of infected mice with Berenil, a trypanocidal drug, restored the development of CIA-associated clinical symptoms. Interestingly, these data were confirmed by the challenge of immunized DBA/1 prone mice with T. brucei-infected tsetse flies. Together, these results demonstrate that T. brucei infection is impairing the maintenance of the antigen specific plasma B cell pool driving the development of CIA in DBA/1 prone mice.",2015 Jun 25,"['De Trez, Carl', 'Katsandegwaza, Brunette', 'Caljon, Guy', 'Magez, Stefan']",PLoS One,,,True
0fbc383f838f9db0f9146ae8889373a9375ec056,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,True
deabc76cd9ee100c9a4088508bdad5048dc8c839,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
c117f1615a020ad82318becdf8f709f52aeb2efd,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
feca5c689581defdc70a39704fc1ef8bdb4189c8,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
2eaa56f8da9327aa9ed79a7eea423bf116d20117,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
1c1a77f8a0e0befc562a31b44721256478a5fc9e,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
c6d54cceed065d505890921bd3936410b4134c3f,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
98250784b8bce843095839979513899ff18edf9a,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
424606001b632c4148c73e7a2c288a08ff978842,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,True
84c1fe63d284751ee5ff158c8dd19d190f90f541,PMC,Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0131460,PMC4482420,26111186,CC BY,"Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.",2015 Jun 25,"['Ling, Samantha Shi Min', 'Khoo, Lawrence Han Boon', 'Hwang, Le-Ann', 'Yeoh, Khay Guan', 'Ho, Bow']",PLoS One,,,False
57cffb9026a4e37031021f91832d48c79df0fd75,PMC,New Metrics for Evaluating Viral Respiratory Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0131451,PMC4482571,26115403,CC BY,"Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.",2015 Jun 26,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Baric, Ralph S.', 'Ferris, Martin T.']",PLoS One,,,True
e82c458779137caddb713da94ff08b30a1f32b9f,PMC,New Metrics for Evaluating Viral Respiratory Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0131451,PMC4482571,26115403,CC BY,"Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.",2015 Jun 26,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Baric, Ralph S.', 'Ferris, Martin T.']",PLoS One,,,False
5f62bfe3cf650294a86bbf7350cc918f82ec4419,PMC,New Metrics for Evaluating Viral Respiratory Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0131451,PMC4482571,26115403,CC BY,"Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.",2015 Jun 26,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Baric, Ralph S.', 'Ferris, Martin T.']",PLoS One,,,False
8dc531b6289f49c6a17ead3a723e71c2cd34e4f2,PMC,New Metrics for Evaluating Viral Respiratory Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0131451,PMC4482571,26115403,CC BY,"Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.",2015 Jun 26,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Baric, Ralph S.', 'Ferris, Martin T.']",PLoS One,,,False
132ebff69dbef71f408ae161b8ebd53de0f2c9f4,PMC,New Metrics for Evaluating Viral Respiratory Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0131451,PMC4482571,26115403,CC BY,"Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.",2015 Jun 26,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Baric, Ralph S.', 'Ferris, Martin T.']",PLoS One,,,False
67a8a9fcd94c110d8b738ee67328bd76d73fd30c,PMC,New Metrics for Evaluating Viral Respiratory Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0131451,PMC4482571,26115403,CC BY,"Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.",2015 Jun 26,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Baric, Ralph S.', 'Ferris, Martin T.']",PLoS One,,,False
1015f9908a0ba0202d9aa3be842f51fd696be62f,PMC,New Metrics for Evaluating Viral Respiratory Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0131451,PMC4482571,26115403,CC BY,"Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.",2015 Jun 26,"['Menachery, Vineet D.', 'Gralinski, Lisa E.', 'Baric, Ralph S.', 'Ferris, Martin T.']",PLoS One,,,False
b8efd7ebd2057d44c6544e918c3631ac395c7fb2,PMC,Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs,http://dx.doi.org/10.1371/journal.ppat.1005016,PMC4482612,26115029,CC0,"The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against the filovirus surface glycoprotein (GP) have been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal antibodies (mAbs) have been described against Ebola virus. In contrast, relatively few have been described against Marburg virus. Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different Marburg virus (MARV) strains. Surprisingly, two of the mAbs raised against MARV GP also cross-react with the mucin-deleted GP cores of all tested ebolaviruses (Ebola, Sudan, Bundibugyo, Reston), but these epitopes are masked differently by the mucin-like domains themselves. The most efficacious mAbs in this panel were found to recognize a novel “wing” feature on the GP2 subunit that is unique to Marburg and does not exist in Ebola. Two of these anti-wing antibodies confer 90 and 100% protection, respectively, one hour post-exposure in mice challenged with MARV.",2015 Jun 26,"['Fusco, Marnie L.', 'Hashiguchi, Takao', 'Cassan, Robyn', 'Biggins, Julia E.', 'Murin, Charles D.', 'Warfield, Kelly L.', 'Li, Sheng', 'Holtsberg, Frederick W.', 'Shulenin, Sergey', 'Vu, Hong', 'Olinger, Gene G.', 'Kim, Do H.', 'Whaley, Kevin J.', 'Zeitlin, Larry', 'Ward, Andrew B.', 'Nykiforuk, Cory', 'Aman, M. Javad', 'Berry, Jody', 'Saphire, Erica Ollmann']",PLoS Pathog,,,True
77b8307c0de7ad71378665456b43e4185d5e5477,PMC,Economic Assessment of FMDv Releases from the National Bio and Agro Defense Facility,http://dx.doi.org/10.1371/journal.pone.0129134,PMC4482686,26114546,CC BY,"This study evaluates the economic consequences of hypothetical foot-and-mouth disease releases from the future National Bio and Agro Defense Facility in Manhattan, Kansas. Using an economic framework that estimates the impacts to agricultural firms and consumers, quantifies costs to non-agricultural activities in the epidemiologically impacted region, and assesses costs of response to the government, we find the distribution of economic impacts to be very significant. Furthermore, agricultural firms and consumers bear most of the impacts followed by the government and the regional non-agricultural firms.",2015 Jun 26,"['Pendell, Dustin L.', 'Marsh, Thomas L.', 'Coble, Keith H.', 'Lusk, Jayson L.', 'Szmania, Sara C.']",PLoS One,,,True
389b75fa8272ae7d2ab3d90ae8c1edbdf55c0463,PMC,Sequence-Specific Fidelity Alterations Associated with West Nile Virus Attenuation in Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1005009,PMC4482725,26114757,CC BY,"High rates of error-prone replication result in the rapid accumulation of genetic diversity of RNA viruses. Recent studies suggest that mutation rates are selected for optimal viral fitness and that modest variations in replicase fidelity may be associated with viral attenuation. Arthropod-borne viruses (arboviruses) are unique in their requirement for host cycling and may necessitate substantial genetic and phenotypic plasticity. In order to more thoroughly investigate the correlates, mechanisms and consequences of arbovirus fidelity, we selected fidelity variants of West Nile virus (WNV; Flaviviridae, Flavivirus) utilizing selection in the presence of a mutagen. We identified two mutations in the WNV RNA-dependent RNA polymerase associated with increased fidelity, V793I and G806R, and a single mutation in the WNV methyltransferase, T248I, associated with decreased fidelity. Both deep-sequencing and in vitro biochemical assays confirmed strain-specific differences in both fidelity and mutational bias. WNV fidelity variants demonstrated host-specific alterations to replicative fitness in vitro, with modest attenuation in mosquito but not vertebrate cell culture. Experimental infections of colonized and field populations of Cx. quinquefaciatus demonstrated that WNV fidelity alterations are associated with a significantly impaired capacity to establish viable infections in mosquitoes. Taken together, these studies (i) demonstrate the importance of allosteric interactions in regulating mutation rates, (ii) establish that mutational spectra can be both sequence and strain-dependent, and (iii) display the profound phenotypic consequences associated with altered replication complex function of flaviviruses.",2015 Jun 26,"['Van Slyke, Greta A.', 'Arnold, Jamie J.', 'Lugo, Alex J.', 'Griesemer, Sara B.', 'Moustafa, Ibrahim M.', 'Kramer, Laura D.', 'Cameron, Craig E.', 'Ciota, Alexander T.']",PLoS Pathog,,,True
1b2079db92924c2ee758d437394789b4822d0327,PMC,"Temporal Trends of In-Hospital Mortality in Patients Treated with Intra-Aortic Balloon Pumping: A Nationwide Population Study in Taiwan, 1998-2008",http://dx.doi.org/10.1371/journal.pone.0131575,PMC4483178,26115413,CC BY,"Intra-aortic balloon pumping (IABP) is widely used for hemodynamic support in critical patients with cardiogenic shock (CS). We examined whether the in-hospital mortality of patients in Taiwan treated with IABP has recently declined. We used Taiwan’s National Health Insurance Research Database to retrospectively review the in-hospital all-cause mortality of 9952 (7146 men [71.8%]) 18-year-old and older patients treated with IABP between 1998 and 2008. The mortality rate was 13.84% (n = 1377). The urbanization levels of the hospitals, and the number of days in the intensive care unit, of hospitalization, and of IABP treatment, and prior percutaneous coronary intervention (PCI) were associated with mortality. Seven thousand six hundred thirty-five patients (76.72%) underwent coronary artery bypass grafting (CABG) surgery, and 576 (5.79%) underwent high-risk PCI with IABP treatment. The number of patients treated with IABP significantly increased during this decade (p(trend) < 0.0001), the in-hospital all-cause mortality for patients treated with IABP significantly decreased (p(trend) = 0.0243), but the in-hospital all-cause mortality of patients who underwent CABG and PCI plus IABP did not decrease. In conclusion, the in-hospital mortality rate of IABP treatment decreased annually in Taiwan during the study period. However, high-risk patients who underwent coronary revascularization with IABP had a higher and unstable in-hospital mortality rate.",2015 Jun 26,"['Ho, Chung-Han', 'Chen, Zhih-Cherng', 'Chu, Chin-Chen', 'Wang, Jhi-Joung', 'Chiang, Chun-Yen']",PLoS One,,,True
4e83f87fdf5b15fb7962c1b6235b520817924a9b,PMC,Entry Inhibition of Influenza Viruses with High Mannose Binding Lectin ESA-2 from the Red Alga Eucheuma serra through the Recognition of Viral Hemagglutinin,http://dx.doi.org/10.3390/md13063454,PMC4483639,26035023,CC BY,"Lectin sensitivity of the recent pandemic influenza A virus (H1N1-2009) was screened for 12 lectins with various carbohydrate specificity by a neutral red dye uptake assay with MDCK cells. Among them, a high mannose (HM)-binding anti-HIV lectin, ESA-2 from the red alga Eucheuma serra, showed the highest inhibition against infection with an EC(50) of 12.4 nM. Moreover, ESA-2 exhibited a wide range of antiviral spectrum against various influenza strains with EC(50)s of pico molar to low nanomolar levels. Besides ESA-2, HM-binding plant lectin ConA, fucose-binding lectins such as fungal AOL from Aspergillus oryzae and AAL from Aleuria aurantia were active against H1N1-2009, but the potency of inhibition was of less magnitude compared with ESA-2. Direct interaction between ESA-2 and a viral envelope glycoprotein, hemagglutinin (HA), was demonstrated by ELISA assay. This interaction was effectively suppressed by glycoproteins bearing HM-glycans, indicating that ESA-2 binds to the HA of influenza virus through HM-glycans. Upon treatment with ESA-2, no viral antigens were detected in the host cells, indicating that ESA-2 inhibited the initial steps of virus entry into the cells. ESA-2 would thus be useful as a novel microbicide to prevent penetration of viruses such as HIV and influenza viruses to the host cells.",2015 May 29,"['Sato, Yuichiro', 'Morimoto, Kinjiro', 'Kubo, Takanori', 'Sakaguchi, Takemasa', 'Nishizono, Akira', 'Hirayama, Makoto', 'Hori, Kanji']",Mar Drugs,,,True
c7f5828ffb5dbc51bda8427bc64056b6eeb1afb0,PMC,Immunological Response to Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex: An RNA-Sequence Analysis of the Bronchial Lymph Node Transcriptome,http://dx.doi.org/10.1371/journal.pone.0131459,PMC4484807,26121276,CC BY,"Susceptibility to bovine respiratory disease (BRD) is multi-factorial and is influenced by stress in conjunction with infection by both bacterial and viral pathogens. While vaccination is broadly used in an effort to prevent BRD, it is far from being fully protective and cases diagnosed from a combination of observed clinical signs without any attempt at identifying the causal pathogens are usually treated with antibiotics. Dairy and beef cattle losses from BRD are profound worldwide and genetic studies have now been initiated to elucidate host loci which underlie susceptibility with the objective of enabling molecular breeding to reduce disease prevalence. In this study, we employed RNA sequencing to examine the bronchial lymph node transcriptomes of controls and beef cattle which had individually been experimentally challenged with bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Pasteurella multocida, Mannheimia haemolytica or Mycoplasma bovis to identify the genes that are involved in the bovine immune response to infection. We found that 142 differentially expressed genes were located in previously described quantitative trait locus regions associated with risk of BRD. Mutations affecting the expression or amino acid composition of these genes may affect disease susceptibility and could be incorporated into molecular breeding programs. Genes involved in innate immunity were generally found to be differentially expressed between the control and pathogen-challenged animals suggesting that variation in these genes may lead to a heritability of susceptibility that is pathogen independent. However, we also found pathogen-specific expression profiles which suggest that host genetic variation for BRD susceptibility is pathogen dependent.",2015 Jun 29,"['Tizioto, Polyana C.', 'Kim, JaeWoo', 'Seabury, Christopher M.', 'Schnabel, Robert D.', 'Gershwin, Laurel J.', 'Van Eenennaam, Alison L.', 'Toaff-Rosenstein, Rachel', 'Neibergs, Holly L.', None, 'Taylor, Jeremy F.']",PLoS One,,,True
974446ae540829dc1b4c7ce8ea1b8dd3843fb3dc,PMC,Specificity and Strain-Typing Capabilities of Nanorod Array-Surface Enhanced Raman Spectroscopy for Mycoplasma pneumoniae Detection,http://dx.doi.org/10.1371/journal.pone.0131831,PMC4487258,26121242,CC0,"Mycoplasma pneumoniae is a cell wall-less bacterial pathogen of the human respiratory tract that accounts for > 20% of all community-acquired pneumonia (CAP). At present the most effective means for detection and strain-typing is quantitative polymerase chain reaction (qPCR), which can exhibit excellent sensitivity and specificity but requires separate tests for detection and genotyping, lacks standardization between available tests and between labs, and has limited practicality for widespread, point-of-care use. We have developed and previously described a silver nanorod array-surface enhanced Raman Spectroscopy (NA-SERS) biosensing platform capable of detecting M. pneumoniae with statistically significant specificity and sensitivity in simulated and true clinical throat swab samples, and the ability to distinguish between reference strains of the two main genotypes of M. pneumoniae. Furthermore, we have established a qualitative lower endpoint of detection for NA-SERS of < 1 genome equivalent (cell/μl) and a quantitative multivariate detection limit of 5.3 ± 1 cells/μl. Here we demonstrate using partial least squares- discriminatory analysis (PLS-DA) of sample spectra that NA-SERS correctly identified M. pneumoniae clinical isolates from globally diverse origins and distinguished these from a panel of 12 other human commensal and pathogenic mycoplasma species with 100% cross-validated statistical accuracy. Furthermore, PLS-DA correctly classified by strain type all 30 clinical isolates with 96% cross-validated accuracy for type 1 strains, 98% cross-validated accuracy for type 2 strains, and 90% cross-validated accuracy for type 2V strains.",2015 Jun 29,"['Henderson, Kelley C.', 'Benitez, Alvaro J.', 'Ratliff, Amy E.', 'Crabb, Donna M.', 'Sheppard, Edward S.', 'Winchell, Jonas M.', 'Dluhy, Richard A.', 'Waites, Ken B.', 'Atkinson, T. Prescott', 'Krause, Duncan C.']",PLoS One,,,True
5688011525aeb581afabe204b64d4da24257aff1,PMC,Emergence of porcine epidemic diarrhea virus in southern Germany,http://dx.doi.org/10.1186/s12917-015-0454-1,PMC4487554,26135732,CC BY,"BACKGROUND: Over the last years, porcine epidemic diarrhea virus (PEDV) has caused devastating enteric diseases in the US and several countries in Asia, while outbreaks in Europe have only been reported sporadically since the 1980s. At present, only insufficient information is available on currently circulating PEDV strains in Europe and their impact on the European swine industry. In this case report, we present epidemic outbreaks of porcine epidemic diarrhea in three farms in South-Western Germany. CASE PRESENTATION: Epidemic outbreaks of diarrhea affecting pigs of all age groups were reported in three farms, one fattening farm and two piglet producing farms, in South-Western Germany between May and November 2014. In the fattening farm yellowish, watery diarrhea without evidence of mucus or blood was associated with a massive reduction of feed consumption. Severity of clinical signs and mortality in young suckling pigs varied significantly between the two affected sow farms. While mortality in suckling piglets reached almost 70 % in one sow herd, no increase in suckling piglet mortality was observed in the second sow farm. In all three cases, PEDV was confirmed in feces and small intestines by RT-qPCR. Phylogenetic analyses based on full-length PEDV genomes revealed high identity among strains from all three herds. Moreover, the German strains showed very high nucleotide identity (99.4 %) with a variant of PEDV (OH851) that was isolated in the United States in January 2014. This strain with insertions and deletions in the S-gene (so called INDEL strains) was reported to show lower virulence. Slightly lower identities were found with other strains from the US and Asia. CONCLUSION: Phylogenetic information on the distribution of PEDV strains in Europe is severely lacking. In this case report we demonstrate that acute outbreaks of PEDV occurred in southern Germany in 2014. Current strains were clearly different from isolates found in the 1980s and were closely related to a PEDV variant found in the US in 2014. Moreover, the present case report indicates that variant strains of PEDV, containing insertions and deletions in the S gene, which were reported to be of lower virulence, might be able to cause high mortality in suckling piglets.",2015 Jul 2,"['Stadler, Julia', 'Zoels, Susanne', 'Fux, Robert', 'Hanke, Dennis', 'Pohlmann, Anne', 'Blome, Sandra', 'Weissenböck, Herbert', 'Weissenbacher-Lang, Christiane', 'Ritzmann, Mathias', 'Ladinig, Andrea']",BMC Vet Res,,,True
9e17fa07642900d9491bf957db97cbe70bc39610,PMC,Monoclonal Antibody Combinations that Present Synergistic Neutralizing Activity: A Platform for Next-Generation Anti-Toxin Drugs,http://dx.doi.org/10.3390/toxins7061854,PMC4488679,26035486,CC BY,"Monoclonal antibodies (MAbs) are among the fastest-growing therapeutics and are being developed for a broad range of indications, including the neutralization of toxins, bacteria and viruses. Nevertheless, MAbs potency is still relatively low when compared to conventional polyclonal Ab preparations. Moreover, the efficacy of an individual neutralizing MAb may significantly be hampered by the potential absence or modification of its target epitope in a mutant or subtype of the infectious agent. These limitations of individual neutralizing MAbs can be overcome by using oligoclonal combinations of several MAbs with different specificities to the target antigen. Studies conducted in our lab and by others show that such combined MAb preparation may present substantial synergy in its potency over the calculated additive potency of its individual MAb components. Moreover, oligoclonal preparation is expected to be better suited to compensating for reduced efficacy due to epitope variation. In this review, the synergistic neutralization properties of combined oligoclonal Ab preparations are described. The effect of Ab affinity, autologous Fc fraction, and targeting a critical number of epitopes, as well as the unexpected contribution of non-neutralizing clones to the synergistic neutralizing effect are presented and discussed.",2015 May 29,"['Diamant, Eran', 'Torgeman, Amram', 'Ozeri, Eyal', 'Zichel, Ran']",Toxins (Basel),,,True
9450e90f9c678f1eb0ce33caac814ebc1b2e97e7,PMC,The Emerging Roles of Viroporins in ER Stress Response and Autophagy Induction during Virus Infection,http://dx.doi.org/10.3390/v7062749,PMC4488716,26053926,CC BY,"Viroporins are small hydrophobic viral proteins that oligomerize to form aqueous pores on cellular membranes. Studies in recent years have demonstrated that viroporins serve important functions during virus replication and contribute to viral pathogenicity. A number of viroporins have also been shown to localize to the endoplasmic reticulum (ER) and/or its associated membranous organelles. In fact, replication of most RNA viruses is closely linked to the ER, and has been found to cause ER stress in the infected cells. On the other hand, autophagy is an evolutionarily conserved “self-eating” mechanism that is also observed in cells infected with RNA viruses. Both ER stress and autophagy are also known to modulate a wide variety of signaling pathways including pro-inflammatory and innate immune response, thereby constituting a major aspect of host-virus interactions. In this review, the potential involvement of viroporins in virus-induced ER stress and autophagy will be discussed.",2015 Jun 4,"['Fung, To Sing', 'Torres, Jaume', 'Liu, Ding Xiang']",Viruses,,,True
a2b0f19c4b1270624987ede418ab8da1e8b55cdf,PMC,Protein-Protein Interactions of Viroporins in Coronaviruses and Paramyxoviruses: New Targets for Antivirals?,http://dx.doi.org/10.3390/v7062750,PMC4488717,26053927,CC BY,"Viroporins are members of a rapidly growing family of channel-forming small polypeptides found in viruses. The present review will be focused on recent structural and protein-protein interaction information involving two viroporins found in enveloped viruses that target the respiratory tract; (i) the envelope protein in coronaviruses and (ii) the small hydrophobic protein in paramyxoviruses. Deletion of these two viroporins leads to viral attenuation in vivo, whereas data from cell culture shows involvement in the regulation of stress and inflammation. The channel activity and structure of some representative members of these viroporins have been recently characterized in some detail. In addition, searches for protein-protein interactions using yeast-two hybrid techniques have shed light on possible functional roles for their exposed cytoplasmic domains. A deeper analysis of these interactions should not only provide a more complete overview of the multiple functions of these viroporins, but also suggest novel strategies that target protein-protein interactions as much needed antivirals. These should complement current efforts to block viroporin channel activity.",2015 Jun 4,"['Torres, Jaume', 'Surya, Wahyu', 'Li, Yan', 'Liu, Ding Xiang']",Viruses,,,True
b02612aa65049060e0a24064db96105458ac083b,PMC,IFITMs from Mycobacteria Confer Resistance to Influenza Virus When Expressed in Human Cells,http://dx.doi.org/10.3390/v7062759,PMC4488726,26075508,CC BY,"Interferon induced transmembrane proteins (IFITMs) found in vertebrates restrict infections by specific viruses. IFITM3 is known to be essential for restriction of influenza virus infections in both mice and humans. Vertebrate IFITMs are hypothesized to have derived from a horizontal gene transfer from bacteria to a primitive unicellular eukaryote. Since bacterial IFITMs share minimal amino acid identity with human IFITM3, we hypothesized that examination of bacterial IFITMs in human cells would provide insight into the essential characteristics necessary for antiviral activity of IFITMs. We examined IFITMs from Mycobacterium avium and Mycobacterium abscessus for potential antiviral activity. Both of these IFITMs conferred a moderate level of resistance to influenza virus in human cells, identifying them as functional homologues of IFITM3. Analysis of sequence elements shared by bacterial IFITMs and IFITM3 identified two hydrophobic domains, putative S-palmitoylation sites, and conserved phenylalanine residues associated with IFITM3 interactions, which are all necessary for IFITM3 antiviral activity. We observed that, like IFITM3, bacterial IFITMs were S-palmitoylated, albeit to a lesser degree. We also demonstrated the ability of a bacterial IFITM to co-immunoprecipitate with IFITM3 suggesting formation of a complex, and also visualized strong co-localization of bacterial IFITMs with IFITM3. However, the mycobacterial IFITMs lack the endocytic-targeting motif conserved in vertebrate IFITM3. As such, these bacterial proteins, when expressed alone, had diminished colocalization with cathepsin B-positive endolysosomal compartments that are the primary site of IFITM3-dependent influenza virus restriction. Though the precise evolutionary origin of vertebrate IFITMs is not known, our results support a model whereby transfer of a bacterial IFITM gene to eukaryotic cells may have provided a selective advantage against viral infection that was refined through the course of vertebrate evolution to include more robust signals for S-palmitoylation and localization to sites of endocytic virus trafficking.",2015 Jun 12,"['Melvin, William J.', 'McMichael, Temet M.', 'Chesarino, Nicholas M.', 'Hach, Jocelyn C.', 'Yount, Jacob S.']",Viruses,,,True
9aed1e2e3dc529e3863b89a60bb4e377e8c3a3e6,PMC,Viral Membrane Channels: Role and Function in the Virus Life Cycle,http://dx.doi.org/10.3390/v7062771,PMC4488738,26110585,CC BY,"Viroporins are small, hydrophobic trans-membrane viral proteins that oligomerize to form hydrophilic pores in the host cell membranes. These proteins are crucial for the pathogenicity and replication of viruses as they aid in various stages of the viral life cycle, from genome uncoating to viral release. In addition, the ion channel activity of viroporin causes disruption in the cellular ion homeostasis, in particular the calcium ion. Fluctuation in the calcium level triggers the activation of the host defensive programmed cell death pathways as well as the inflammasome, which in turn are being subverted for the viruses’ replication benefits. This review article summarizes recent developments in the functional investigation of viroporins from various viruses and their contributions to viral replication and virulence.",2015 Jun 23,"['Sze, Ching Wooen', 'Tan, Yee-Joo']",Viruses,,,True
471239798c6ed87995720ee1a73092b8b79b9549,PMC,Characterisation of Structural Proteins from Chronic Bee Paralysis Virus (CBPV) Using Mass Spectrometry,http://dx.doi.org/10.3390/v7062774,PMC4488741,26110588,CC BY,"Chronic bee paralysis virus (CBPV) is the etiological agent of chronic paralysis, an infectious and contagious disease in adult honeybees. CBPV is a positive single-stranded RNA virus which contains two major viral RNA fragments. RNA 1 (3674 nt) and RNA 2 (2305 nt) encode three and four putative open reading frames (ORFs), respectively. RNA 1 is thought to encode the viral RNA-dependent RNA polymerase (RdRp) since the amino acid sequence derived from ORF 3 shares similarities with the RdRP of families Nodaviridae and Tombusviridae. The genomic organization of CBPV and in silico analyses have suggested that RNA 1 encodes non-structural proteins, while RNA 2 encodes structural proteins, which are probably encoded by ORFs 2 and 3. In this study, purified CBPV particles were used to characterize virion proteins by mass spectrometry. Several polypeptides corresponding to proteins encoded by ORF 2 and 3 on RNA 2 were detected. Their role in the formation of the viral capsid is discussed.",2015 Jun 23,"['Chevin, Aurore', 'Coutard, Bruno', 'Blanchard, Philippe', 'Dabert-Gay, Anne-Sophie', 'Ribière-Chabert, Magali', 'Thiéry, Richard']",Viruses,,,True
c59c9a2c6315ed5aa7c437d1943fd94518119fd8,PMC,A Novel Chimeric Anti-PA Neutralizing Antibody for Postexposure Prophylaxis and Treatment of Anthrax,http://dx.doi.org/10.1038/srep11776,PMC4488766,26134518,CC BY,"Anthrax is a highly lethal infectious disease caused by the bacterium Bacillus anthracis, and the associated shock is closely related to the lethal toxin (LeTx) produced by the bacterium. The central role played by the 63 kDa protective antigen (PA63) region of LeTx in the pathophysiology of anthrax makes it an excellent therapeutic target. In the present study, a human/murine chimeric IgG mAb, hmPA6, was developed by inserting murine antibody variable regions into human constant regions using antibody engineering technology. hmPA6 expressed in 293F cells could neutralize LeTx both in vitro and in vivo. At a dose of 0.3 mg/kg, it could protect all tested rats from a lethal dose of LeTx. Even administration of 0.6 mg/kg hmPA6 48 h before LeTx challenge protected all tested rats. The results indicate that hmPA6 is a potential candidate for clinical application in anthrax treatment.",2015 Jul 2,"['Xiong, Siping', 'Tang, Qi', 'Liang, Xudong', 'Zhou, Tingting', 'Yang, Jin', 'Liu, Peng', 'Chen, Ya', 'Wang, Changjun', 'Feng, Zhenqing', 'Zhu, Jin']",Sci Rep,,,True
35f06fe8870be0c3cd7f0e9b47872a59c7590d7d,PMC,Modulation of the Immune Response to Respiratory Viruses by Vitamin D,http://dx.doi.org/10.3390/nu7064240,PMC4488782,26035247,CC BY,"Background: Vitamin D deficiency has been shown to be independently associated with increased risk of viral acute respiratory infection (ARI) in a number of observational studies, and meta-analysis of clinical trials of vitamin D supplementation for prevention of ARI has demonstrated protective effects. Several cellular studies have investigated the effects of vitamin D metabolites on immune responses to respiratory viruses, but syntheses of these reports are lacking. Scope: In this article, we review the literature reporting results of in vitro experiments investigating immunomodulatory actions of vitamin D metabolites in human respiratory epithelial cells infected with respiratory viruses. Key findings: Vitamin D metabolites do not consistently influence replication or clearance of rhinovirus, respiratory syncytial virus (RSV) or influenza A virus in human respiratory epithelial cell culture, although they do modulate expression and secretion of type 1 interferon, chemokines including CXCL8 and CXCL10 and pro-inflammatory cytokines, such as TNF and IL-6. Future research: More studies are needed to clarify the effects of vitamin D metabolites on respiratory virus-induced expression of cell surface markers mediating viral entry and bacterial adhesion to respiratory epithelial cells.",2015 May 29,"['Greiller, Claire L.', 'Martineau, Adrian R.']",Nutrients,,,True
5db737c9e3b8b52dd6c4778e9ade92d2ff9fadbe,PMC,Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice,http://dx.doi.org/10.1186/s13054-015-0983-9,PMC4490661,26067826,CC BY,"INTRODUCTION: Provision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice. METHODS: Nine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation. RESULTS: Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group, p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment. CONCLUSIONS: Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-0983-9) contains supplementary material, which is available to authorized users.",2015 Jun 11,"['Nosaka, Nobuyuki', 'Yashiro, Masato', 'Yamada, Mutsuko', 'Fujii, Yosuke', 'Tsukahara, Hirokazu', 'Liu, Keyue', 'Nishibori, Masahiro', 'Matsukawa, Akihiro', 'Morishima, Tsuneo']",Crit Care,,,True
bae2a5c3432eed55a087174498b80fe9f9725943,PMC,Public health round-up,http://dx.doi.org/10.2471/BLT.15.010715,PMC4490818,,CC BY,,2015 Jul 1,,Bull World Health Organ,,,False
5a717164844c095a4fb195350b44048059245b21,PMC,"Intranasal and oral vaccination with protein-based antigens: advantages, challenges and formulation strategies",http://dx.doi.org/10.1007/s13238-015-0164-2,PMC4491048,25944045,CC BY,"Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low immunogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-015-0164-2) contains supplementary material, which is available to authorized users.",2015 Jul 6,"['Wang, Shujing', 'Liu, Huiqin', 'Zhang, Xinyi', 'Qian, Feng']",Protein Cell,,,False
ae44f456afccca76e1eec1637ce1af6041956c64,PMC,"Intranasal and oral vaccination with protein-based antigens: advantages, challenges and formulation strategies",http://dx.doi.org/10.1007/s13238-015-0164-2,PMC4491048,25944045,CC BY,"Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low immunogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-015-0164-2) contains supplementary material, which is available to authorized users.",2015 Jul 6,"['Wang, Shujing', 'Liu, Huiqin', 'Zhang, Xinyi', 'Qian, Feng']",Protein Cell,,,True
2ba96cb3fe11b62cac4ae9816383256395239409,PMC,Factors associated with uptake of influenza vaccine in people aged 50 to 64 years in Hong Kong: a case–control study,http://dx.doi.org/10.1186/s12889-015-1990-0,PMC4491862,26148496,CC BY,"BACKGROUND: In Hong Kong, people aged 50–64 years were added as a recommended priority group (recommended group) for influenza vaccination by the Department of Health (DH) starting from 2011/12 onwards. The coverage rate of influenza vaccination for this age group was suboptimal at 8.5 % in 2012/13. This study investigates the factors associated with the uptake of influenza vaccination among adults in Hong Kong aged 50–64 years. METHODS: A case–control study was conducted in communities by street intercept interviews from 17 July to 15 August 2013. Cases were adults aged 50–64 years who had received the influenza vaccine in 2011/12 or 2012/13, while controls were the same as the cases, except they had not received the influenza vaccine in 2011/12 or 2012/13. Multiple logistic regression analysis was performed on the data to explore the associations between vaccination status and the variables. RESULTS: Six hundred and four respondents in total were interviewed and included in the analysis. There were 193 cases (vaccinated) and 411 controls (non-vaccinated), with a case-to-control ratio of 1:2.1. The following were strongly associated with vaccination compared to other factors: ‘eligible for free government vaccine’ (OR6.38, 95 % CI, 3.43-11.87, p < 0.001); ‘willing to receive flu vaccination for free’ (OR4.84, 95 % CI, 2.13-11.03, p < 0.001); ‘perceived having severe or moderate symptoms when contracting flu’ (OR2.90, 95 % CI, 1.21-6.97, p = 0.02), and ‘convenient to reach a vaccination location’ (OR2.87, 95 % CI, 1.06-7.74, p = 0.04). The majority of the cases (80.8 %) and controls (93.9 %) were not aware that they belonged to a recommended group for influenza vaccination and most (>80 %) were willing to be vaccinated if it was free. CONCLUSIONS: Factors related to free and convenient vaccination, the perception of the severity of symptoms when contracting influenza had a comparatively strong association with influenza vaccination uptake amongst 50–64 year olds, compared to other factors.",2015 Jul 7,"['Yeung, May PS', 'Ng, Stephen Kam-Cheung', 'Tong, Edmond Tak Fai', 'Chan, Stephen Sek-Kam', 'Coker, Richard']",BMC Public Health,,,True
6eb0faeda9396efaf96674c33b40395012a01e0a,PMC,Single-Stranded DNA Aptamers against Pathogens and Toxins: Identification and Biosensing Applications,http://dx.doi.org/10.1155/2015/419318,PMC4493287,26199940,CC BY,"Molecular recognition elements (MREs) can be short sequences of single-stranded DNA, RNA, small peptides, or antibody fragments. They can bind to user-defined targets with high affinity and specificity. There has been an increasing interest in the identification and application of nucleic acid molecular recognition elements, commonly known as aptamers, since they were first described in 1990 by the Gold and Szostak laboratories. A large number of target specific nucleic acids MREs and their applications are currently in the literature. This review first describes the general methodologies used in identifying single-stranded DNA (ssDNA) aptamers. It then summarizes advancements in the identification and biosensing application of ssDNA aptamers specific for bacteria, viruses, their associated molecules, and selected chemical toxins. Lastly, an overview of the basic principles of ssDNA aptamer-based biosensors is discussed.",2015 Jun 23,"['Hong, Ka Lok', 'Sooter, Letha J.']",Biomed Res Int,,,True
3ca43ade94501268228e5239d1717d4f6333d462,PMC,Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial,http://dx.doi.org/10.3390/vaccines1040398,PMC4494211,26344340,CC BY,"2013 marks a milestone year for plasmid DNA vaccine development as a first-in-class cytomegalovirus (CMV) DNA vaccine enters pivotal phase 3 testing. This vaccine consists of two plasmids expressing CMV antigens glycoprotein B (gB) and phosphoprotein 65 (pp65) formulated with a CRL1005 poloxamer and benzalkonium chloride (BAK) delivery system designed to enhance plasmid expression. The vaccine’s planned initial indication under investigation is for prevention of CMV reactivation in CMV-seropositive (CMV(+)) recipients of an allogeneic hematopoietic stem cell transplant (HCT). A randomized, double-blind placebo-controlled phase 2 proof-of-concept study provided initial evidence of the safety of this product in CMV(+) HCT recipients who underwent immune ablation conditioning regimens. This study revealed a significant reduction in viral load endpoints and increased frequencies of pp65-specific interferon-γ-producing T cells in vaccine recipients compared to placebo recipients. The results of this endpoint-defining trial provided the basis for defining the primary and secondary endpoints of a global phase 3 trial in HCT recipients. A case study is presented here describing the development history of this vaccine from product concept to initiation of the phase 3 trial.",2013 Sep 25,"['Smith, Larry R.', 'Wloch, Mary K.', 'Chaplin, Jennifer A.', 'Gerber, Michele', 'Rolland, Alain P.']",Vaccines (Basel),,,True
f78956e70c8bd1756ffb24ae47c35c3217bed384,PMC,Peptide Vaccine: Progress and Challenges,http://dx.doi.org/10.3390/vaccines2030515,PMC4494216,26344743,CC BY,"Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.",2014 Jul 2,"['Li, Weidang', 'Joshi, Medha D.', 'Singhania, Smita', 'Ramsey, Kyle H.', 'Murthy, Ashlesh K.']",Vaccines (Basel),,,True
653c1744be45d5e3ba3e9fb48edf6c6997976324,PMC,Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications,http://dx.doi.org/10.3390/vaccines2040755,PMC4494248,26344890,CC BY,"The LC16m8 strain of vaccinia virus, the active ingredient in the Japanese smallpox vaccine, was derived from the Lister/Elstree strain. LC16m8 is replication-competent and has been administered to over 100,000 infants and 3,000 adults with no serious adverse reactions. Despite this outstanding safety profile, the occurrence of spontaneously-generated large plaque-forming virulent LC16m8 revertants following passage in cell culture is a major drawback. We identified the gene responsible for the reversion and deleted the gene (B5R) from LC16m8 to derive LC16m8Δ. LC16m8∆ is non-pathogenic in immunodeficient severe combined immunodeficiency (SCID) mice, genetically-stable and does not reverse to a large-plaque phenotype upon passage in cell culture, even under conditions in which most LC16m8 populations are replaced by revertants. Moreover, LC16m8∆ is >500-fold more effective than the non-replicating vaccinia virus (VV), Modified Vaccinia Ankara (MVA), at inducing murine immune responses against pathogenic VV. LC16m8∆, which expresses the SIV gag gene, also induced anti-Gag CD8(+) T-cells more efficiently than MVA and another non-replicating VV, Dairen I minute-pock variants (DIs). Moreover, LC16m8∆ expressing HIV-1 Env in combination with a Sendai virus vector induced the production of anti-Env antibodies and CD8(+) T-cells. Thus, the safety and efficacy of LC16m8∆ mean that it represents an outstanding platform for the development of human vaccine vectors.",2014 Oct 17,"['Kidokoro, Minoru', 'Shida, Hisatoshi']",Vaccines (Basel),,,True
6be6ca48112c227ce80a36601ea8b464edbf1367,PMC,"Developing Universal Influenza Vaccines: Hitting the Nail, Not Just on the Head",http://dx.doi.org/10.3390/vaccines3020239,PMC4494343,26343187,CC BY,"Influenza viruses have a huge impact on public health. Current influenza vaccines need to be updated annually and protect poorly against antigenic drift variants or novel emerging subtypes. Vaccination against influenza can be improved in two important ways, either by inducing more broadly protective immune responses or by decreasing the time of vaccine production, which is relevant especially during a pandemic outbreak. In this review, we outline the current efforts to develop so-called “universal influenza vaccines”, describing antigens that may induce broadly protective immunity and novel vaccine production platforms that facilitate timely availability of vaccines.",2015 Mar 26,"['Wiersma, Lidewij C. M.', 'Rimmelzwaan, Guus F.', 'de Vries, Rory D.']",Vaccines (Basel),,,True
d51485f32ff85186571e9ec9de6d517f9180abe9,PMC,The Use of a Shelter Software (a) to Track Frequency and Selected Risk Factors for Feline Upper Respiratory Infection,http://dx.doi.org/10.3390/ani5020161,PMC4494401,26479227,CC BY,"SIMPLE SUMMARY: Feline upper respiratory infection is a common disease in animal shelters. Without monitoring, effective control and prevention is difficult. We looked at a software system (a) used in shelters across the United States to determine if it can be used to track URI frequency and risk factors in a population. Reports from the software system (a) were compared to data collected manually. This showed that data currently collected were not useful for tracking URI frequency and risk factors. However, potential exists to increase the practicality and usefulness of this shelter software system to monitor URI and other diseases. ABSTRACT: Objective—Feline upper respiratory infection (URI) is a common, multi-factorial infectious disease syndrome endemic to many animal shelters. Although a significant cause of morbidity and mortality in shelter cats, URI is seldom formally monitored in shelter cat populations. Without monitoring, effective control and prevention of this often endemic disease is difficult. We looked at an integrated case management software system (a) for animal care organizations, widely used in shelters across the United States. Shelter staff routinely enter information regarding individual animals and disease status, but do not commonly use the software system to track frequency of disease. The purpose of this study was to determine if the software system (a) can be used to track URI frequency and selected risk factors in a population, and to evaluate the quality and completeness of the data as currently collected in a shelter. Design (type of study)—Descriptive Survey. Animals (or Sample)—317 cats in an animal shelter. Procedures—Reports from the software system (a) containing data regarding daily inventory, daily intake, animal identification, location, age, vaccination status, URI diagnosis and URI duration were evaluated. The reports were compared to data collected manually by an observer (Ann Therese Kommedal) to assess discrepancies, completeness, timeliness, availability and accuracy. Data were collected 6 days a week over a 4 week period. Results—Comparisons between the software system (a) reports and manually collected reports showed that 93% of inventory reports were complete and of these 99% were accurate. Fifty-two percent of the vaccination reports were complete, of which 97% were accurate. The accuracy of the software system’s age reports was 76%. Two-hundred and twenty-three cats were assigned a positive or negative URI diagnosis by the observer. The predictive value of the URI status in the software system (a) was below 60% both for positive and negative URI diagnosis. Conclusions and Clinical Relevance—data currently collected and entered into the software systems in the study shelter, was not useful for tracking URI frequency and risk factors, due to issues with both data quality and capture. However, the potential exists to increase the practicality and usefulness of this shelter software system to monitor URI and other diseases. Relevant data points, i.e., health status at intake and outcome, vaccination date and status, as well as age, should be made mandatory to facilitate more useful data collection and reporting.",2015 Mar 25,"['Kommedal, Ann Therese', 'Wagner, Denae', 'Hurley, Kate']",Animals (Basel),,,True
a5d44eaf14b7ed5402af3501540147d36b314824,PMC,Large Eddy Simulation of Air Escape through a Hospital Isolation Room Single Hinged Doorway—Validation by Using Tracer Gases and Simulated Smoke Videos,http://dx.doi.org/10.1371/journal.pone.0130667,PMC4494857,26151865,CC BY,"The use of hospital isolation rooms has increased considerably in recent years due to the worldwide outbreaks of various emerging infectious diseases. However, the passage of staff through isolation room doors is suspected to be a cause of containment failure, especially in case of hinged doors. It is therefore important to minimize inadvertent contaminant airflow leakage across the doorway during such movements. To this end, it is essential to investigate the behavior of such airflows, especially the overall volume of air that can potentially leak across the doorway during door-opening and human passage. Experimental measurements using full-scale mock-ups are expensive and labour intensive. A useful alternative approach is the application of Computational Fluid Dynamics (CFD) modelling using a time-resolved Large Eddy Simulation (LES) method. In this study simulated air flow patterns are qualitatively compared with experimental ones, and the simulated total volume of air that escapes is compared with the experimentally measured volume. It is shown that the LES method is able to reproduce, at room scale, the complex transient airflows generated during door-opening/closing motions and the passage of a human figure through the doorway between two rooms. This was a basic test case that was performed in an isothermal environment without ventilation. However, the advantage of the CFD approach is that the addition of ventilation airflows and a temperature difference between the rooms is, in principle, a relatively simple task. A standard method to observe flow structures is dosing smoke into the flow. In this paper we introduce graphical methods to simulate smoke experiments by LES, making it very easy to compare the CFD simulation to the experiments. The results demonstrate that the transient CFD simulation is a promising tool to compare different isolation room scenarios without the need to construct full-scale experimental models. The CFD model is able to reproduce the complex airflows and estimate the volume of air escaping as a function of time. In this test, the calculated migrated air volume in the CFD model differed by 20% from the experimental tracer gas measurements. In the case containing only a hinged door operation, without passage, the difference was only 10%.",2015 Jul 7,"['Saarinen, Pekka E.', 'Kalliomäki, Petri', 'Tang, Julian W.', 'Koskela, Hannu']",PLoS One,,,True
c63e2bbb0915e7d4d40813d58286d51e80453507,PMC,Efficient generation of influenza virus with a mouse RNA polymerase I-driven all-in-one plasmid,http://dx.doi.org/10.1186/s12985-015-0321-5,PMC4495709,26093583,CC BY,"BACKGROUND: The current influenza vaccines are effective against seasonal influenza, but cannot be manufactured in a timely manner for a sudden pandemic or to be cost-effective to immunize huge flocks of birds. We propose a novel influenza vaccine composing a bacterial carrier and a plasmid cargo. In the immunized subjects, the bacterial carrier invades and releases its cargo into host cells where the plasmid expresses viral RNAs and proteins for reconstitution of attenuated influenza virus. Here we aimed to construct a mouse PolI-driven plasmid for efficient production of influenza virus. RESULTS: A plasmid was constructed to express all influenza viral RNAs and proteins. This all-in-one plasmid resulted in 10(5)–10(6) 50 % tissue culture infective dose (TCID(50))/mL of influenza A virus in baby hamster kidney (BHK-21) cells on the third day post-transfection, and also reconstituted influenza virus in Madin–Darby canine kidney (MDCK) and Chinese hamster ovary (CHO) cells. A 6-unit plasmid was constructed by deleting the HA and NA cassettes from the all-in-one plasmid. Cotransfection of BHK-21 cells with the 6-unit plasmid and the two other plasmids encoding the HA or NA genes resulted in influenza virus titers similar to those produced by the 1-plasmid method. CONCLUSIONS: An all-in-one plasmid and a 3-plasmid murine PolI-driven reverse genetics systems were developed, and efficiently reconstituted influenza virus in BHK-21 cells. The all-in-one plasmid may serve as a tool to determine the factors inhibiting virus generation from a large size plasmid. In addition, we recommend a simple and robust “1 + 2” approach to generate influenza vaccine seed virus.",2015 Jun 22,"['Zhang, Xiangmin', 'Curtiss, Roy']",Virol J,,,True
9f1936809149b1ca45c64b1468ba966bcdc4e331,PMC,"Outbreak of febrile illness caused by coxsackievirus A4 in a nursery school in Beijing, China",http://dx.doi.org/10.1186/s12985-015-0325-1,PMC4495935,26084565,CC BY,"BACKGROUND: Coxsackievirus A4 (CV-A4) is classified as human enterovirus A according to its serotype. CV-A4, an etiological agent of hand, foot, and mouth disease, affects children worldwide and can circulate in closed environments such as schools and hospitals for long periods. FINDINGS: An outbreak of febrile illness at a nursery school in Beijing, China, was confirmed to be caused by CV-A4. Phylogenetic analysis of the complete genome of the isolated strain showed that the virus belongs to the same cluster as the predominant CV-A4 strain in China. This outbreak was controlled by effective measures. CONCLUSIONS: The early identification of the pathogen and timely intervention may be the most critical factors in controlling an outbreak caused by CV-A4 in a preschool.",2015 Jun 18,"['Li, Jin-Song', 'Dong, Xiao-Gen', 'Qin, Meng', 'Xie, Zhi-Ping', 'Gao, Han-Chun', 'Yang, Jun-Yong', 'Yang, Xiao-Xin', 'Li, Dan-Di', 'Li, Jie', 'Duan, Zhao-Jun']",Virol J,,,True
21133fab598928cee990ee06d660b1d00f317175,PMC,Determining the Provincial and National Burden of Influenza-Associated Severe Acute Respiratory Illness in South Africa Using a Rapid Assessment Methodology,http://dx.doi.org/10.1371/journal.pone.0132078,PMC4496064,26154306,CC0,"Local disease burden data are necessary to set national influenza vaccination policy. In 2010 the population of South Africa was 50 million and the HIV prevalence was 11%. We used a previously developed methodology to determine severe influenza burden in South Africa. Hospitalized severe acute respiratory illness (SARI) incidence was calculated, stratified by HIV status, for four age groups using data from population-based surveillance in one site situated in Gauteng Province for 2009–2011. These rates were adjusted for each of the remaining 8 provinces based on their prevalence of risk factors for pneumonia and healthcare-seeking behavior. We estimated non-hospitalized influenza-associated SARI from healthcare utilization surveys at two sites and used the percent of SARI cases positive for influenza from sentinel surveillance to derive the influenza-associated SARI rate. We applied rates of hospitalized and non-hospitalized influenza-associated SARI to census data to calculate the national number of cases. The percent of SARI cases that tested positive for influenza ranged from 7–17% depending on age group, year, province and HIV status. In 2010, there were an estimated 21,555 total severe influenza cases in HIV-uninfected individuals and 13,876 in HIV-infected individuals. In 2011, there were an estimated 29,892 total severe influenza cases in HIV-uninfected individuals and 17,289 in HIV-infected individuals. The incidence of influenza-associated SARI was highest in children <5 years and was higher in HIV-infected than HIV-uninfected persons in all age groups. Influenza virus was associated with a substantial amount of severe disease, especially in young children and HIV-infected populations in South Africa.",2015 Jul 8,"['Murray, Jillian', 'Cohen, Adam', 'Walaza, Sibongile', 'Groome, Michelle', 'Madhi, Shabir', 'Variava, Ebrahim', 'Kahn, Kathleen', 'Dawood, Halima', 'Tempia, Stefano', 'Tshangela, Akhona', 'Venter, Marietje', 'Feikin, Daniel', 'Cohen, Cheryl']",PLoS One,,,True
db0761035838151a0b08a13888982ee36641b467,PMC,The Complex Role of STAT3 in Viral Infections,http://dx.doi.org/10.1155/2015/272359,PMC4496485,26199948,CC BY,"Signal transducer and activators of transcription-3 (STAT3) regulates diverse biological functions including cell growth, differentiation, and apoptosis. In addition, STAT3 plays a key role in regulating host immune and inflammatory responses and in the pathogenesis of many cancers. Several studies reported differential regulation of STAT3 in a range of viral infections. Interestingly, STAT3 appears to direct seemingly contradictory responses and both pro- and antiviral roles of STAT3 have been described. This review summarized the currently known functions of STAT3 in the regulation of viral replication and pathogenesis of viral infections. Some of the key unanswered questions and the gap in our current understanding of the role of STAT3 in viral pathogenesis are discussed.",2015 Jun 25,"Kuchipudi, Suresh V.",J Immunol Res,,,True
a0b13baa35ff28471952e5011f9411529d217f50,PMC,Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs,http://dx.doi.org/10.1186/s13567-015-0209-9,PMC4496848,26159607,CC BY,"Classical swine fever (CSF) causes major losses in pig farming, with various degrees of disease severity. Efficient live attenuated vaccines against classical swine fever virus (CSFV) are used routinely in endemic countries. However, despite intensive vaccination programs in these areas for more than 20 years, CSF has not been eradicated. Molecular epidemiology studies in these regions suggests that the virus circulating in the field has evolved under the positive selection pressure exerted by the immune response to the vaccine, leading to new attenuated viral variants. Recent work by our group demonstrated that a high proportion of persistently infected piglets can be generated by early postnatal infection with low and moderately virulent CSFV strains. Here, we studied the immune response to a hog cholera lapinised virus vaccine (HCLV), C-strain, in six-week-old persistently infected pigs following post-natal infection. CSFV-negative pigs were vaccinated as controls. The humoral and interferon gamma responses as well as the CSFV RNA loads were monitored for 21 days post-vaccination. No vaccine viral RNA was detected in the serum samples and tonsils from CSFV postnatally persistently infected pigs for 21 days post-vaccination. Furthermore, no E2-specific antibody response or neutralising antibody titres were shown in CSFV persistently infected vaccinated animals. Likewise, no of IFN-gamma producing cell response against CSFV or PHA was observed. To our knowledge, this is the first report demonstrating the absence of a response to vaccination in CSFV persistently infected pigs.",2015 Jul 9,"['Muñoz-González, Sara', 'Perez-Simó, Marta', 'Muñoz, Marta', 'Bohorquez, José Alejandro', 'Rosell, Rosa', 'Summerfield, Artur', 'Domingo, Mariano', 'Ruggli, Nicolas', 'Ganges, Llilianne']",Vet Res,,,True
e97dc3686befac553f8f1a09459ae59b089b4b8b,PMC,Proteomic analysis of purified turkey adenovirus 3 virions,http://dx.doi.org/10.1186/s13567-015-0214-z,PMC4497381,26159706,CC BY,"Turkey adenovirus 3 (TAdV-3) causes high mortality and significant economic losses to the turkey industry. However, little is known about the molecular determinants required for viral replication and pathogenesis. Moreover, TAdV-3 does not grow well in cell culture, thus detailed structural studies of the infectious particle is particularly challenging. To develop a better understanding of virus-host interactions, we performed a comprehensive proteomic analysis of proteinase K treated purified TAdV-3 virions isolated from spleens of infected turkeys, by utilizing one-dimensional liquid chromatography mass spectrometry. Our analysis resulted in the identification of 13 viral proteins associated with TAdV-3 virions including a novel uncharacterized TaV3gp04 protein. Further, we detected 18 host proteins in purified virions, many of which are involved in cell-to cell spread, cytoskeleton dynamics and virus replication. Notably, seven of these host proteins have not yet been reported to be present in any other purified virus. In addition, five of these proteins are known antiviral host restriction factors. The availability of reagents allowed us to identify two cellular proteins (collagen alpha-1 (VI) chain and haemoglobin) in the purified TAdV-3 preparations. These results represent the first comprehensive proteomic profile of TAdV-3 and may provide information for illustrating TAdV-3 replication and pathogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-015-0214-z) contains supplementary material, which is available to authorized users.",2015 Jul 9,"['Kumar, Pankaj', 'van den Hurk, Jan', 'Ayalew, Lisanework E.', 'Gaba, Amit', 'Tikoo, Suresh K.']",Vet Res,,,True
76241f85fbee07bdf466214c02c4bccd79706436,PMC,Novel circular single-stranded DNA viruses identified in marine invertebrates reveal high sequence diversity and consistent predicted intrinsic disorder patterns within putative structural proteins,http://dx.doi.org/10.3389/fmicb.2015.00696,PMC4498126,26217327,CC BY,"Viral metagenomics has recently revealed the ubiquitous and diverse nature of single-stranded DNA (ssDNA) viruses that encode a conserved replication initiator protein (Rep) in the marine environment. Although eukaryotic circular Rep-encoding ssDNA (CRESS-DNA) viruses were originally thought to only infect plants and vertebrates, recent studies have identified these viruses in a number of invertebrates. To further explore CRESS-DNA viruses in the marine environment, this study surveyed CRESS-DNA viruses in various marine invertebrate species. A total of 27 novel CRESS-DNA genomes, with Reps that share less than 60.1% identity with previously reported viruses, were recovered from 21 invertebrate species, mainly crustaceans. Phylogenetic analysis based on the Rep revealed a novel clade of CRESS-DNA viruses that included approximately one third of the marine invertebrate associated viruses identified here and whose members may represent a novel family. Investigation of putative capsid proteins (Cap) encoded within the eukaryotic CRESS-DNA viral genomes from this study and those in GenBank demonstrated conserved patterns of predicted intrinsically disordered regions (IDRs), which can be used to complement similarity-based searches to identify divergent structural proteins within novel genomes. Overall, this study expands our knowledge of CRESS-DNA viruses associated with invertebrates and explores a new tool to evaluate divergent structural proteins encoded by these viruses.",2015 Jul 10,"['Rosario, Karyna', 'Schenck, Ryan O.', 'Harbeitner, Rachel C.', 'Lawler, Stephanie N.', 'Breitbart, Mya']",Front Microbiol,,,True
6044c9d0aae3d02db03c409496ca81f8f83ebeab,PMC,Meta-genomic analysis of toilet waste from long distance flights; a step towards global surveillance of infectious diseases and antimicrobial resistance,http://dx.doi.org/10.1038/srep11444,PMC4498435,26161690,CC BY,"Human populations worldwide are increasingly confronted with infectious diseases and antimicrobial resistance spreading faster and appearing more frequently. Knowledge regarding their occurrence and worldwide transmission is important to control outbreaks and prevent epidemics. Here, we performed shotgun sequencing of toilet waste from 18 international airplanes arriving in Copenhagen, Denmark, from nine cities in three world regions. An average of 18.6 Gb (14.8 to 25.7 Gb) of raw Illumina paired end sequence data was generated, cleaned, trimmed and mapped against reference sequence databases for bacteria and antimicrobial resistance genes. An average of 106,839 (0.06%) reads were assigned to resistance genes with genes encoding resistance to tetracycline, macrolide and beta-lactam resistance genes as the most abundant in all samples. We found significantly higher abundance and diversity of genes encoding antimicrobial resistance, including critical important resistance (e.g. bla(CTX-M)) carried on airplanes from South Asia compared to North America. Presence of Salmonella enterica and norovirus were also detected in higher amounts from South Asia, whereas Clostridium difficile was most abundant in samples from North America. Our study provides a first step towards a potential novel strategy for global surveillance enabling simultaneous detection of multiple human health threatening genetic elements, infectious agents and resistance genes.",2015 Jul 10,"['Nordahl Petersen, Thomas', 'Rasmussen, Simon', 'Hasman, Henrik', 'Carøe, Christian', 'Bælum, Jacob', 'Charlotte Schultz, Anna', 'Bergmark, Lasse', 'Svendsen, Christina A.', 'Lund, Ole', 'Sicheritz-Pontén, Thomas', 'Aarestrup, Frank M.']",Sci Rep,,,True
f4ac2b1e9b9523671d7c38c27a19f1eec2e15d75,PMC,Meta-genomic analysis of toilet waste from long distance flights; a step towards global surveillance of infectious diseases and antimicrobial resistance,http://dx.doi.org/10.1038/srep11444,PMC4498435,26161690,CC BY,"Human populations worldwide are increasingly confronted with infectious diseases and antimicrobial resistance spreading faster and appearing more frequently. Knowledge regarding their occurrence and worldwide transmission is important to control outbreaks and prevent epidemics. Here, we performed shotgun sequencing of toilet waste from 18 international airplanes arriving in Copenhagen, Denmark, from nine cities in three world regions. An average of 18.6 Gb (14.8 to 25.7 Gb) of raw Illumina paired end sequence data was generated, cleaned, trimmed and mapped against reference sequence databases for bacteria and antimicrobial resistance genes. An average of 106,839 (0.06%) reads were assigned to resistance genes with genes encoding resistance to tetracycline, macrolide and beta-lactam resistance genes as the most abundant in all samples. We found significantly higher abundance and diversity of genes encoding antimicrobial resistance, including critical important resistance (e.g. bla(CTX-M)) carried on airplanes from South Asia compared to North America. Presence of Salmonella enterica and norovirus were also detected in higher amounts from South Asia, whereas Clostridium difficile was most abundant in samples from North America. Our study provides a first step towards a potential novel strategy for global surveillance enabling simultaneous detection of multiple human health threatening genetic elements, infectious agents and resistance genes.",2015 Jul 10,"['Nordahl Petersen, Thomas', 'Rasmussen, Simon', 'Hasman, Henrik', 'Carøe, Christian', 'Bælum, Jacob', 'Charlotte Schultz, Anna', 'Bergmark, Lasse', 'Svendsen, Christina A.', 'Lund, Ole', 'Sicheritz-Pontén, Thomas', 'Aarestrup, Frank M.']",Sci Rep,,,True
a1d863f8297bd6185abeb6564af22eac8bdd3fd3,PMC,Development of Recombinase Polymerase Amplification Assays for Detection of Orientia tsutsugamushi or Rickettsia typhi,http://dx.doi.org/10.1371/journal.pntd.0003884,PMC4498641,26161793,CC0,"Sensitive, specific and rapid diagnostic tests for the detection of Orientia tsutsugamushi (O. tsutsugamushi) and Rickettsia typhi (R. typhi), the causative agents of scrub typhus and murine typhus, respectively, are necessary to accurately and promptly diagnose patients and ensure that they receive proper treatment. Recombinase polymerase amplification (RPA) assays using a lateral flow test (RPA-nfo) and real-time fluorescent detection (RPA-exo) were developed targeting the 47-kDa gene of O. tsutsugamushi or 17 kDa gene of R. typhi. The RPA assay was capable of detecting O. tsutsugamushi or R. typhi at levels comparable to that of the quantitative PCR method. Both the RPA-nfo and RPA-exo methods performed similarly with regards to sensitivity when detecting the 17 kDa gene of R. typhi. On the contrary, RPA-exo performed better than RPA-nfo in detecting the 47 kDa gene of O. tsutsugamushi. The clinical performance of the O. tsutsugamushi RPA assay was evaluated using either human patient samples or infected mouse samples. Eight out of ten PCR confirmed positives were determined positive by RPA, and all PCR confirmed negative samples were negative by RPA. Similar results were obtained for R. typhi spiked patient sera. The assays were able to differentiate O. tsutsugamushi and R. typhi from other phylogenetically related bacteria as well as mouse and human DNA. Furthermore, the RPA-nfo reaction was completed in 20 minutes at 37(o)C followed by a 10 minute incubation at room temperature for development of an immunochromatographic strip. The RPA-exo reaction was completed in 20 minutes at 39(o)C. The implementation of a cross contamination proof cassette to detect the RPA-nfo fluorescent amplicons provided an alternative to regular lateral flow detection strips, which are more prone to cross contamination. The RPA assays provide a highly time-efficient, sensitive and specific alternative to other methods for diagnosing scrub typhus or murine typhus.",2015 Jul 10,"['Chao, Chien-Chung', 'Belinskaya, Tatyana', 'Zhang, Zhiwen', 'Ching, Wei-Mei']",PLoS Negl Trop Dis,,,True
ae0144eb4ec61e7765eed001bc8a9c775cd31b67,PMC,"Public Health Responses to Reemergence of Animal Rabies, Taiwan, July 16–December 28, 2013",http://dx.doi.org/10.1371/journal.pone.0132160,PMC4498755,26162074,CC BY,"Taiwan had been free of indigenous human and animal rabies case since canine rabies was eliminated in 1961. In July 2013, rabies was confirmed among three wild ferret-badgers, prompting public health response to prevent human rabies cases. This descriptive study reports the immediate response to the reemergence of rabies in Taiwan. Response included enhanced surveillance for human rabies cases by testing stored cerebrospinal fluids (CSF) from patients with encephalitides of unknown cause by RT-PCR, prioritizing vaccine use for postexposure prophylaxis (PEP) during periods of vaccine shortage and subsequent expansion of PEP, surveillance of animal bites using information obtained from vaccine application, roll out of preexposure prophylaxis (PrEP) with vaccine stock restoration, surveillance for adverse events following immunization (AEFI), and ensuring surge capacity to respond to general public inquiries by phone and training for healthcare professionals. Enhanced surveillance for human rabies found no cases after testing 205 stored CSF specimens collected during January 2010–July 2013. During July 16 to December 28, 2013, we received 8,241 rabies PEP application; 6,634 (80.5%) were consistent with recommendations. Among the 6,501persons who received at least one dose of rabies vaccine postexposure, 4,953 (76.2%) persons who were bitten by dogs; only 59 (0.9%) persons were bitten by ferret-badgers. During the study period, 6,247 persons received preexposure prophylaxis. There were 23 reports of AEFI; but no anaphylaxis, Guillain-Barré syndrome, or acute disseminated encephalomyelitis were found. During the study period, there were 40,312 calls to the Taiwan Centers for Disease Control hotline, of which, 8,692 (22%) were related to rabies. Recent identification of rabies among ferret-badgers in a previously rabies-free country prompted rapid response. To date, no human rabies has been identified. Continued multifaceted surveillance and interministerial collaboration are crucial to achieve the goal of rabies-free status in Taiwan.",2015 Jul 10,"['Huang, Angela Song-En', 'Chen, Wan-Chin', 'Huang, Wan-Ting', 'Huang, Shih-Tse', 'Lo, Yi-Chun', 'Wei, Sung-Hsi', 'Kuo, Hung-Wei', 'Chan, Pei-Chun', 'Hung, Min-Nan', 'Liu, Yu-Lun', 'Mu, Jung-Jung', 'Yang, Jyh-Yuan', 'Liu, Ding-Ping', 'Chou, Jih-Haw', 'Chuang, Jen-Hsiang', 'Chang, Feng-Yee']",PLoS One,,,True
d135acb9011d47a0f0d9e2b6542cb86539042fdf,PMC,Evaluation of farm-level parameters derived from animal movements for use in risk-based surveillance programmes of cattle in Switzerland,http://dx.doi.org/10.1186/s12917-015-0468-8,PMC4499910,26170195,CC BY,"BACKGROUND: This study focused on the descriptive analysis of cattle movements and farm-level parameters derived from cattle movements, which are considered to be generically suitable for risk-based surveillance systems in Switzerland for diseases where animal movements constitute an important risk pathway. METHODS: A framework was developed to select farms for surveillance based on a risk score summarizing 5 parameters. The proposed framework was validated using data from the bovine viral diarrhoea (BVD) surveillance programme in 2013. RESULTS: A cumulative score was calculated per farm, including the following parameters; the maximum monthly ingoing contact chain (in 2012), the average number of animals per incoming movement, use of mixed alpine pastures and the number of weeks in 2012 a farm had movements registered. The final score for the farm depended on the distribution of the parameters. Different cut offs; 50, 90, 95 and 99 %, were explored. The final scores ranged between 0 and 5. Validation of the scores against results from the BVD surveillance programme 2013 gave promising results for setting the cut off for each of the five selected farm level criteria at the 50th percentile. Restricting testing to farms with a score ≥ 2 would have resulted in the same number of detected BVD positive farms as testing all farms, i.e., the outcome of the 2013 surveillance programme could have been reached with a smaller survey. CONCLUSIONS: The seasonality and time dependency of the activity of single farms in the networks requires a careful assessment of the actual time period included to determine farm level criteria. However, selecting farms in the sample for risk-based surveillance can be optimized with the proposed scoring system. The system was validated using data from the BVD eradication program. The proposed method is a promising framework for the selection of farms according to the risk of infection based on animal movements.",2015 Jul 14,"['Schärrer, Sara', 'Widgren, Stefan', 'Schwermer, Heinzpeter', 'Lindberg, Ann', 'Vidondo, Beatriz', 'Zinsstag, Jakob', 'Reist, Martin']",BMC Vet Res,,,True
733c577e6a1dea9aab436bce4d918f08dfd27371,PMC,Ultraviolet Light (UV) Inactivation of Porcine Parvovirus in Liquid Plasma and Effect of UV Irradiated Spray Dried Porcine Plasma on Performance of Weaned Pigs,http://dx.doi.org/10.1371/journal.pone.0133008,PMC4501813,26171968,CC BY,"A novel ultraviolet light irradiation (UV-C, 254 nm) process was designed as an additional safety feature for manufacturing of spray dried porcine plasma (SDPP). In Exp. 1, three 10-L batches of bovine plasma were inoculated with 10(5.2±0.12) tissue culture infectious dose 50 (TCID(50)) of porcine parvovirus (PPV) per mL of plasma and subjected to UV-C ranging from 0 to 9180 J/L. No viable PPV was detected in bovine plasma by micro-titer assay in SK6 cell culture after UV-C at 2295 J/L. In Exp. 2, porcine plasma was subjected to UV-C (3672 J/L), then spray dried and mixed in complete mash diets. Diets were a control without SDPP (Control), UV-C SDPP either at 3% (UVSDPP3) or 6% (UVSDPP6) and non-UV-C SDPP at 3% (SDPP3) or 6% (SDPP6). Diets were fed ad libitum to 320 weaned pigs (26 d of age; 16 pens/diet; 4 pigs/pen) for 14 d after weaning and a common diet was fed d 15 to 28. During d 0 to 14, pigs fed UVSDPP3, UVSDPP6, or SDPP6 had higher (P < 0.05) weight gain and feed intake than control. During d 0 to 28, pigs fed UVSDPP3 and UVSDPP6 had higher (P < 0.05) weight gain and feed intake than control and SDPP3, and SDPP6 had higher (P < 0.05) feed intake than control. Also, pigs fed UVSDPP had higher (P < 0.05) weight gain than pigs fed SDPP. In conclusion, UV-C inactivated PPV in liquid plasma and UVSDPP used in pig feed had no detrimental effects on pig performance.",2015 Jul 14,"['Polo, Javier', 'Rodríguez, Carmen', 'Ródenas, Jesús', 'Russell, Louis E.', 'Campbell, Joy M.', 'Crenshaw, Joe D.', 'Torrallardona, David', 'Pujols, Joan']",PLoS One,,,True
0d8ae2d2ad6343782f8f7c078d00c14206f16230,PMC,Research Driven by Curiosity: The Journey from Basic Molecular Biology and Virology to Studies of Human Pathogenic Coronaviruses,http://dx.doi.org/10.1371/journal.ppat.1005023,PMC4501819,26172373,CC BY,,2015 Jul 14,"Perlman, Stanley",PLoS Pathog,,,False
c1722fc1da22b2ccf5565ccf81a1677c2994aeee,PMC,EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT,http://dx.doi.org/10.1038/srep11494,PMC4503950,26177797,CC BY,"Lung carcinogenesis is a complex process that occurs in unregulated inflammatory environment. EGCG has been extensively investigated as a multi-targeting anti-tumor and anti-inflammatory compound. In this study, we demonstrated a novel mechanism by which EGCG reverses the neutrophil elastase-induced migration of A549 cells. We found that neutrophil elastase directly triggered human adenocarcinoma A549 cell migration and that EGCG suppressed the elevation of tumor cell migration induced by neutrophil elastase. We observed that EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity based on the CDOCKER algorithm, MD stimulation by GROMACS, SPR assay and elastase enzymatic activity assay. As the natural inhibitor of neutrophil elastase, α1-antitrypsin is synthesized in tumor cells. We further demonstrated that the expression of α1-antitrypsin was up-regulated after EGCG treatment in neutrophil elastase-treated A549 cells. We preliminarily discovered that the EGCG-mediated induction of α1-antitrypsin expression might be correlated with the regulatory effect of EGCG on the PI3K/Akt pathway. Overall, our results suggest that EGCG ameliorates the neutrophil elastase-induced migration of A549 cells. The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway.",2015 Jul 16,"['Xiaokaiti, Yilixiati', 'Wu, Haoming', 'Chen, Ya', 'Yang, Haopeng', 'Duan, Jianhui', 'Li, Xin', 'Pan, Yan', 'Tie, Lu', 'Zhang, Liangren', 'Li, Xuejun']",Sci Rep,,,True
fb6b4f00d820aad697369de4f7f29b709541e973,PMC,Identification and pathogenicity of a variant porcine epidemic diarrhea virus field strain with reduced virulence,http://dx.doi.org/10.1186/s12985-015-0314-4,PMC4504071,26063495,CC BY,"BACKGROUND: Since 2010, a variant Porcine epidemic diarrhea virus (PEDV), which causes an acute, highly contagious, and devastating viral enteric disease with a high mortality rate in suckling pigs, broke out in China and spread rapidly to neighboring countries, even to the North America. This virus gradually became the main subtype of PEDV worldwide. However, there were no reports of mild pathogenicity of a variant porcine epidemic diarrhea virus in China. FINDINGS: In 2013, a PEDV-positive sample from a sow with very mild clinical sign was used to inoculate in Vero cells to isolate the virus. This PEDV field strain, designated FL2013 strain, was successfully propagated and genetically characterized. The phylogenetic trees based upon either the complete genome or S gene showed that the FL2013 strain belongs to the genogroup G2b. The S gene of FL2013 has a 7-aa deletion (FEKVHVQ) in the C-terminus comparison with the other G2 PEDV sequences. Further comparative pathology study indicated that the FL2013 strain had reduced virulence to newborn piglets. CONCLUSIONS: A novel variant PEDV strain FL2013 with reduced virulence, as determined by the pathological study, was identified from east China. This strain is closely related to the genogroup- 2 PEDV strains prevalent in the U.S. and China currently, but had a short deletion at the 3′- end of the spike gene.",2015 Jun 12,"['Zhang, Xiangbin', 'Pan, Yongfei', 'Wang, Dongdong', 'Tian, Xiaoyan', 'Song, Yanhua', 'Cao, Yongchang']",Virol J,,,True
333a04fb2ab37297b4591e7d6179fd731f5c1bf3,PMC,Clinical and molecular investigation of a canine distemper outbreak and vector-borne infections in a group of rescue dogs imported from Hungary to Switzerland,http://dx.doi.org/10.1186/s12917-015-0471-0,PMC4504088,26179635,CC BY,"BACKGROUND: Canine distemper virus (CDV) is a major pathogen of dogs and wild carnivores worldwide. In Switzerland, distemper in domestic dogs is rarely reported. In recent years, the import of dogs from Eastern Europe to Switzerland has steadily increased. In the present study, we describe a distemper outbreak in 15 rescue dogs that were imported from Hungary to Switzerland by an animal welfare organisation. The data on vaccination and medical history were recorded (14 dogs), and the samples were collected to investigate CDV and vector-borne infections (13 dogs) and canine parvovirus infection (12 dogs). The dogs were monitored for six months. RESULTS: One dog was euthanised directly after import. Thirteen dogs showed clinical signs after arrival, i.e., diarrhoea (57 %), coughing (43 %) and nasal and/or ocular discharge (21 %); radiographic findings that were compatible with bronchopneumonia were present in four dogs. CDV infection was diagnosed in 11 dogs (85 %); 10 dogs (91 %) tested PCR-positive in conjunctival swabs. Vector-borne infections (Babesia spp., Leishmania infantum, Dirofilaria immitis) were found in 4 dogs (31 %). Three dogs were hospitalized, and six dogs received ambulatory therapy for up to two months until recovery. None of the dogs developed neurological disease. CDV shedding was detected for a period of up to four months. Because dogs were put under strict quarantine until CDV shedding ceased, CDV did not spread to any other dogs. The CDV isolates showed 99 % sequence identity in the HA gene among each other and belonged to the Arctic-like lineage of CDV. CONCLUSIONS: The present study highlights the imminent risks of spreading contagious viral and vector-borne infections through the non-selective import of sick dogs and dogs with incomplete vaccination from Eastern Europe. CDV shedding was detected for several months after the cessation of clinical signs, which emphasised the roles of asymptomatic carriers in CDV epidemiology. A long-term follow-up using sensitive PCR and strict quarantine measures is of upmost importance in preventing the spread of infection. Dog owners and animal welfare organisations should be educated regarding the importance of complete vaccinations and the impact of dog imports on the spread of viral and vector-borne pathogens.",2015 Jul 16,"['Willi, Barbara', 'Spiri, Andrea M.', 'Meli, Marina L.', 'Grimm, Felix', 'Beatrice, Laura', 'Riond, Barbara', 'Bley, Tim', 'Jordi, Rolf', 'Dennler, Matthias', 'Hofmann-Lehmann, Regina']",BMC Vet Res,,,True
162c064dae8c02e477c00bbcd60b974ae794649f,PMC,Potential Biases in Estimating Absolute and Relative Case-Fatality Risks during Outbreaks,http://dx.doi.org/10.1371/journal.pntd.0003846,PMC4504518,26181387,CC BY,"Estimating the case-fatality risk (CFR)—the probability that a person dies from an infection given that they are a case—is a high priority in epidemiologic investigation of newly emerging infectious diseases and sometimes in new outbreaks of known infectious diseases. The data available to estimate the overall CFR are often gathered for other purposes (e.g., surveillance) in challenging circumstances. We describe two forms of bias that may affect the estimation of the overall CFR—preferential ascertainment of severe cases and bias from reporting delays—and review solutions that have been proposed and implemented in past epidemics. Also of interest is the estimation of the causal impact of specific interventions (e.g., hospitalization, or hospitalization at a particular hospital) on survival, which can be estimated as a relative CFR for two or more groups. When observational data are used for this purpose, three more sources of bias may arise: confounding, survivorship bias, and selection due to preferential inclusion in surveillance datasets of those who are hospitalized and/or die. We illustrate these biases and caution against causal interpretation of differential CFR among those receiving different interventions in observational datasets. Again, we discuss ways to reduce these biases, particularly by estimating outcomes in smaller but more systematically defined cohorts ascertained before the onset of symptoms, such as those identified by forward contact tracing. Finally, we discuss the circumstances in which these biases may affect non-causal interpretation of risk factors for death among cases.",2015 Jul 16,"['Lipsitch, Marc', 'Donnelly, Christl A.', 'Fraser, Christophe', 'Blake, Isobel M.', 'Cori, Anne', 'Dorigatti, Ilaria', 'Ferguson, Neil M.', 'Garske, Tini', 'Mills, Harriet L.', 'Riley, Steven', 'Van Kerkhove, Maria D.', 'Hernán, Miguel A.']",PLoS Negl Trop Dis,,,True
69f5726e6b53f93b94630c1388479879f49f456e,PMC,"Objectives, design and enrollment results from the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure Study (INSPIRE)",http://dx.doi.org/10.1186/s12890-015-0040-0,PMC4506623,26021723,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) during infancy has been consistently associated with an increased risk of childhood asthma. In addition, evidence supports that this relationship is causal. However, the mechanisms through which RSV contributes to asthma development are not understood. The INSPIRE (Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure) study objectives are to: 1) characterize the host phenotypic response to RSV infection in infancy and the risk of recurrent wheeze and asthma, 2) identify the immune response and lung injury patterns of RSV infection that are associated with the development of early childhood wheezing illness and asthma, and 3) determine the contribution of specific RSV strains to early childhood wheezing and asthma development. This article describes the INSPIRE study, including study aims, design, recruitment results, and enrolled population characteristics. METHODS/DESIGN: The cohort is a population based longitudinal birth cohort of term healthy infants enrolled during the first months of life over a two year period. Respiratory infection surveillance was conducted from November to March of the first year of life, through surveys administered every two weeks. In-person illness visits were conducted if infants met pre-specified criteria for a respiratory illness visit. Infants will be followed annually to ages 3-4 years for assessment of the primary endpoint: wheezing illness. Nasal, urine, stool and blood samples were collected at various time points throughout the study for measurements of host and viral factors that predict wheezing illness. Nested case-control studies will additionally be used to address other primary and secondary hypotheses. DISCUSSION: In the INSPIRE study, 1952 infants (48% female) were enrolled during the two enrollment years and follow-up will continue through 2016. The mean age of enrollment was 60 days. During winter viral season, more than 14,000 surveillance surveys were carried out resulting in 2,103 respiratory illness visits on 1189 infants. First year follow-up has been completed on over 95% percent of participants from the first year of enrollment. With ongoing follow-up for wheezing and childhood asthma outcomes, the INSPIRE study will advance our understanding of the complex causal relationship between RSV infection and early childhood wheezing and asthma.",2015 Apr 30,"['Larkin, Emma K', 'Gebretsadik, Tebeb', 'Moore, Martin L', 'Anderson, Larry J', 'Dupont, William D', 'Chappell, James D', 'Minton, Patricia A', 'Peebles, R Stokes', 'Moore, Paul E', 'Valet, Robert S', 'Arnold, Donald H', 'Rosas-Salazar, Christian', 'Das, Suman R', 'Polack, Fernando P', 'Hartert, Tina V', None]",BMC Pulm Med,,,True
7a9b57f8fdbedfe909d69cf53de24646684624f3,PMC,Functions of the 5′ and 3′ ends of calicivirus genomes,http://dx.doi.org/10.1016/j.virusres.2015.02.002,PMC4509552,25678268,CC BY,"The Caliciviridae family of small positive sense RNA viruses contains a diverse range of pathogens of both man and animals. The molecular mechanisms of calicivirus genome replication and translation have not been as widely studied as many other RNA viruses. With the relatively recent development of robust cell culture and reverse genetics systems for several members of the Caliciviridae family, a more in-depth analysis of the finer detail of the viral life cycle has now been obtained. As a result, the identification and characterization of the role of RNA structures in the calicivirus life cycle has also been possible. This review aims to summarize the current state of knowledge with respect to the role of RNA structures at the termini of calicivirus genomes.",2015 Aug 3,"['Alhatlani, Bader', 'Vashist, Surender', 'Goodfellow, Ian']",Virus Res,,,False
25a160364a2e056a097e4520f64c49c63140da6c,PMC,The Interferon-Inducible Mouse Apolipoprotein L9 and Prohibitins Cooperate to Restrict Theiler’s Virus Replication,http://dx.doi.org/10.1371/journal.pone.0133190,PMC4510265,26196674,CC BY,"Apolipoprotein L9b (Apol9b) is an interferon-stimulated gene (ISG) that has antiviral activity and is weakly expressed in primary mouse neurons as compared to other cell types. Here, we show that both Apol9 isoforms (Apol9b and Apol9a) inhibit replication of Theiler’s murine encephalomyelitis virus (TMEV) but not replication of vesicular stomatitis virus (VSV), Murid herpesvirus-4 (MuHV-4), or infection by a lentiviral vector. Apol9 genes are strongly expressed in mouse liver and, to a lesser extent, in pancreas, adipose tissue and intestine. Their expression is increased by type I interferon and viral infection. In contrast to genuine apolipoproteins that are involved in lipid transport, ApoL9 has an intracytoplasmic localization and does not seem to be secreted. The cytoplasmic localization of ApoL9 is in line with the observation that ApoL9 inhibits the replication step of TMEV infection. In contrast to human ApoL6, ApoL9 did not sensitize cells to apoptosis, in spite of the presence of a conserved putative BH3 domain, required for antiviral activity. ApoL9a and b isoforms interact with cellular prohibitin 1 (Phb1) and prohibitin 2 (Phb2) and this interaction might contribute to ApoL9 antiviral activity. Knocking down Phb2 slightly increased TMEV replication, irrespective of ApoL9 overexpression. The antiviral activity of prohibitins against TMEV contrasts with the pro-viral activity of prohibitins observed for VSV and reported previously for Dengue 2 (DENV-2), Chikungunya (CHIKV) and influenza H5N1 viruses. ApoL9 is thus an example of ISG displaying a narrow antiviral range, which likely acts in complex with prohibitins to restrict TMEV replication.",2015 Jul 21,"['Kreit, Marguerite', 'Vertommen, Didier', 'Gillet, Laurent', 'Michiels, Thomas']",PLoS One,,,True
95b1f681cfe2bb33c6433b07cd38f0ed3ce3667d,PMC,9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate,http://dx.doi.org/10.1038/ncomms8673,PMC4510713,26169044,CC BY,"Sialic acids, terminal sugars of glycoproteins and glycolipids, play important roles in development, cellular recognition processes and host–pathogen interactions. A common modification of sialic acids is 9-O-acetylation, which has been implicated in sialoglycan recognition, ganglioside biology, and the survival and drug resistance of acute lymphoblastic leukaemia cells. Despite many functional implications, the molecular basis of 9-O-acetylation has remained elusive thus far. Following cellular approaches, including selective gene knockout by CRISPR/Cas genome editing, we here show that CASD1—a previously identified human candidate gene—is essential for sialic acid 9-O-acetylation. In vitro assays with the purified N-terminal luminal domain of CASD1 demonstrate transfer of acetyl groups from acetyl-coenzyme A to CMP-activated sialic acid and formation of a covalent acetyl-enzyme intermediate. Our study provides direct evidence that CASD1 is a sialate O-acetyltransferase and serves as key enzyme in the biosynthesis of 9-O-acetylated sialoglycans.",2015 Jul 14,"['Baumann, Anna-Maria T.', 'Bakkers, Mark J. G.', 'Buettner, Falk F. R.', 'Hartmann, Maike', 'Grove, Melanie', 'Langereis, Martijn A.', 'de Groot, Raoul J.', 'Mühlenhoff, Martina']",Nat Commun,,,True
25037be00789070e126164a9f939b64aeede0a64,PMC,9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate,http://dx.doi.org/10.1038/ncomms8673,PMC4510713,26169044,CC BY,"Sialic acids, terminal sugars of glycoproteins and glycolipids, play important roles in development, cellular recognition processes and host–pathogen interactions. A common modification of sialic acids is 9-O-acetylation, which has been implicated in sialoglycan recognition, ganglioside biology, and the survival and drug resistance of acute lymphoblastic leukaemia cells. Despite many functional implications, the molecular basis of 9-O-acetylation has remained elusive thus far. Following cellular approaches, including selective gene knockout by CRISPR/Cas genome editing, we here show that CASD1—a previously identified human candidate gene—is essential for sialic acid 9-O-acetylation. In vitro assays with the purified N-terminal luminal domain of CASD1 demonstrate transfer of acetyl groups from acetyl-coenzyme A to CMP-activated sialic acid and formation of a covalent acetyl-enzyme intermediate. Our study provides direct evidence that CASD1 is a sialate O-acetyltransferase and serves as key enzyme in the biosynthesis of 9-O-acetylated sialoglycans.",2015 Jul 14,"['Baumann, Anna-Maria T.', 'Bakkers, Mark J. G.', 'Buettner, Falk F. R.', 'Hartmann, Maike', 'Grove, Melanie', 'Langereis, Martijn A.', 'de Groot, Raoul J.', 'Mühlenhoff, Martina']",Nat Commun,,,True
638c6b2e4772152a6cba52184c98dec9ca288c16,PMC,A case of bronchiolitis obliterans organizing pneumonia in an HIV-infected Korean patient successfully treated with clarithromycin,http://dx.doi.org/10.1186/s12879-015-1025-6,PMC4512086,26201392,CC BY,"BACKGROUND: Bronchiolitis obliterans organizing pneumonia (BOOP) is a type of diffuse interstitial lung disease characterized by the pathology of fibroblastic plugs in the lumens of the respiratory bronchioles, alveolar ducts, and alveoli. The occurrence of BOOP in human immunodeficiency virus (HIV)-infected patients has rarely been described, and there have been no clinical case reports in Korea. CASE PRESENTATION: A 24-year-old female who had been diagnosed with HIV ten years prior was admitted due to a 1-year history of cough and sputum production and a 3-day history of fever. She had poor adherence to anti-retroviral therapy (ART) due to gastrointestinal troubles. At the time of admission, her CD4 T-cell count was 5 cells/mm(3). A high resolution computed tomography (CT) scan showed tiny centrilobular nodules with a tree-in-bud pattern in both lungs. Bacterial culture, Pneumocystis jirovecii polymerase chain reaction (PCR), Aspergillus galactomannan antigen (Ag) assay, and respiratory virus PCR were negative. Rapid chest x-ray improvement was seen after a 7-day treatment with anti-tuberculosis medication, ceftriaxone, and clarithromycin. Miliary tuberculosis seemed unlikely considering the rapid radiologic improvement and negative tuberculosis PCR results. Due to the unknown etiology, we performed video-assisted thoracoscopic surgery (VATS) to determine the cause of the diffuse lung infiltration. Pathologic findings were consistent with BOOP, while tissue acid-fast bacilli (AFB) stain and tuberculosis PCR results were negative. Tuberculosis medication and intravenous ceftriaxone were discontinued, while treatment with clarithromycin monotherapy was sustained. Five months after discharge, the patient was asymptomatic with a normal chest x-ray and as her adherence to ART improved, her CD4 T-cell count rose to 181 cells/mm(3). Clarithromycin was discontinued at that time and the patient is currently receiving regular outpatient follow-up. CONCLUSION: This case suggests that macrolides are a potential treatment option in HIV-infected patients with mild BOOP. In cases that are otherwise unexplained or unresponsive to treatment, BOOP should be taken into consideration and surgical biopsy performed to confirm a diagnosis of BOOP.",2015 Jul 23,"['Jung, In Young', 'Jeon, Yong Duk', 'Ahn, Mi-young', 'Goag, Eunkyong', 'Lee, EunHye', 'Ahn, Hea Won', 'Ahn, Jin Young', 'Ku, Nam Su', 'Kim, June Myung', 'Choi, Jun Yong']",BMC Infect Dis,,,True
f475c055c4630c81ab519125a20ba96cd3e17e4a,PMC,Enhancing Human Immunodeficiency Virus-Specific CD8(+) T Cell Responses with Heteroclitic Peptides,http://dx.doi.org/10.3389/fimmu.2015.00377,PMC4512150,26257743,CC BY,"Human immunodeficiency virus (HIV)-specific CD8(+) T cells play a critical role in containing HIV replication and delaying disease progression. However, HIV-specific CD8(+) T cells become progressively more “exhausted” as chronic HIV infection proceeds. Symptoms of T cell exhaustion range from expression of inhibitory receptors and selective loss of cytokine production capacity through reduced proliferative potential, impaired differentiation into effector cells and increased susceptibility to apoptosis. While effective combination antiretroviral therapy (cART) durably reduces HIV viremia to undetectable levels, this alone does not restore the full pluripotency of HIV-specific CD8(+) T cells. In a number of studies, a subset of peptide epitope variants categorized as heteroclitic, restimulated more potent cellular immune responses in vitro than did the native, immunizing peptides themselves. This property of heteroclitic peptides has been exploited in experimental cancer and chronic viral infection models to promote clearance of transformed cells and persistent viruses. In this review, we consider the possibility that heteroclitic peptides could improve the efficacy of therapeutic vaccines as part of HIV immunotherapy or eradication strategies. We review literature on heteroclitic peptides and illustrate their potential to beneficially modulate the nature of HIV-specific T cell responses toward those found in the small minority of HIV-infected, aviremic cART-naïve persons termed elite controllers or long-term non-progressors. Our review suggests that the efficacy of HIV vaccines could be improved by identification, testing, and incorporation of heteroclitic variants of native HIV peptide epitopes.",2015 Jul 23,"['Adegoke, Adeolu Oyemade', 'Grant, Michael David']",Front Immunol,,,True
fd4b79d3d28a8c01c635987b474443590c240f4c,PMC,Macrophage Polarization in Virus-Host Interactions,http://dx.doi.org/10.4172/2155-9899.1000311,PMC4512304,26213635,CC BY,"Macrophage involvement in viral infections and antiviral states is common. However, this involvement has not been well-studied in the paradigm of macrophage polarization, which typically has been categorized by the dichotomy of classical (M1) and alternative (M2) statuses. Recent studies have revealed the complexity of macrophage polarization in response to various cellular mediators and exogenous stimuli by adopting a multipolar view to revisit the differential process of macrophages, especially those re-polarized during viral infections. Here, through examination of viral infections targeting macrophages/monocytic cells, we focus on the direct involvement of macrophage polarization during viral infections. Type I and type III interferons (IFNs) are critical in regulation of viral pathogenesis and host antiviral infection; thus, we propose to incorporate IFN-mediated antiviral states into the framework of macrophage polarization. This view is supported by the multifunctional properties of type I IFNs, which potentially elicit and regulate both M1- and M2-polarization in addition to inducing the antiviral state, and by the discoveries of viral mechanisms to adapt and modulate macrophage polarization. Indeed, several recent studies have demonstrated effective prevention of viral diseases through manipulation of macrophage immune statuses.",2015 Apr 27,"['Sang, Yongming', 'Miller, Laura C', 'Blecha, Frank']",J Clin Cell Immunol,,,True
52879771bf3fb8b982308b90d70bebd2485ceaf1,PMC,Sequence-independent characterization of viruses based on the pattern of viral small RNAs produced by the host,http://dx.doi.org/10.1093/nar/gkv587,PMC4513865,26040701,CC BY,"Virus surveillance in vector insects is potentially of great benefit to public health. Large-scale sequencing of small and long RNAs has previously been used to detect viruses, but without any formal comparison of different strategies. Furthermore, the identification of viral sequences largely depends on similarity searches against reference databases. Here, we developed a sequence-independent strategy based on virus-derived small RNAs produced by the host response, such as the RNA interference pathway. In insects, we compared sequences of small and long RNAs, demonstrating that viral sequences are enriched in the small RNA fraction. We also noted that the small RNA size profile is a unique signature for each virus and can be used to identify novel viral sequences without known relatives in reference databases. Using this strategy, we characterized six novel viruses in the viromes of laboratory fruit flies and wild populations of two insect vectors: mosquitoes and sandflies. We also show that the small RNA profile could be used to infer viral tropism for ovaries among other aspects of virus biology. Additionally, our results suggest that virus detection utilizing small RNAs can also be applied to vertebrates, although not as efficiently as to plants and insects.",2015 Jul 27,"['Aguiar, Eric\xa0Roberto\xa0Guimarães\xa0Rocha', 'Olmo, Roenick Proveti', 'Paro, Simona', 'Ferreira, Flavia Viana', 'de\xa0Faria, Isaque\xa0João\xa0da\xa0Silva', 'Todjro, Yaovi\xa0Mathias\xa0Honore', 'Lobo, Francisco Pereira', 'Kroon, Erna Geessien', 'Meignin, Carine', 'Gatherer, Derek', 'Imler, Jean-Luc', 'Marques, João Trindade']",Nucleic Acids Res,,,True
87cb1c3bdd1b8701c07a17f66a17e5d7a55797e5,PMC,Sequence-independent characterization of viruses based on the pattern of viral small RNAs produced by the host,http://dx.doi.org/10.1093/nar/gkv587,PMC4513865,26040701,CC BY,"Virus surveillance in vector insects is potentially of great benefit to public health. Large-scale sequencing of small and long RNAs has previously been used to detect viruses, but without any formal comparison of different strategies. Furthermore, the identification of viral sequences largely depends on similarity searches against reference databases. Here, we developed a sequence-independent strategy based on virus-derived small RNAs produced by the host response, such as the RNA interference pathway. In insects, we compared sequences of small and long RNAs, demonstrating that viral sequences are enriched in the small RNA fraction. We also noted that the small RNA size profile is a unique signature for each virus and can be used to identify novel viral sequences without known relatives in reference databases. Using this strategy, we characterized six novel viruses in the viromes of laboratory fruit flies and wild populations of two insect vectors: mosquitoes and sandflies. We also show that the small RNA profile could be used to infer viral tropism for ovaries among other aspects of virus biology. Additionally, our results suggest that virus detection utilizing small RNAs can also be applied to vertebrates, although not as efficiently as to plants and insects.",2015 Jul 27,"['Aguiar, Eric\xa0Roberto\xa0Guimarães\xa0Rocha', 'Olmo, Roenick Proveti', 'Paro, Simona', 'Ferreira, Flavia Viana', 'de\xa0Faria, Isaque\xa0João\xa0da\xa0Silva', 'Todjro, Yaovi\xa0Mathias\xa0Honore', 'Lobo, Francisco Pereira', 'Kroon, Erna Geessien', 'Meignin, Carine', 'Gatherer, Derek', 'Imler, Jean-Luc', 'Marques, João Trindade']",Nucleic Acids Res,,,True
0511ed1c3e91902ab662c81f8fc20c83a840e8d0,PMC,Risk factors for febrile respiratory illness and mono-viral infections in a semi-closed military environment: a case-control study,http://dx.doi.org/10.1186/s12879-015-1024-7,PMC4514976,26208494,CC BY,"BACKGROUND: Febrile respiratory illness (FRI) results in substantial burden in semi-closed environments. Tackling risk factors may reduce transmission and infection. However, risk factors involved in one setting may not be generalizable in all settings due to differences in climate, residential environment, population genetic and cultural backgrounds. This study aims to identify risk factors of FRI and mono-viral infections in a tropical military environment. METHODS: From year 2009 to 2012, military personnel with temperature ≥37.5 °C, cough and/or sore throat, and personnel with no fever or no respiratory symptoms were recruited as cases and controls, respectively. Subjects provided nasal wash specimens and answered a standardized questionnaire. Resplex assays were used to determine the viral etiologies. Descriptive, univariate and multivariate analyses of the variables were performed using appropriate descriptive tests and logistic regression modelling, respectively, with R program. RESULTS: A total of 7,743 FRI cases and 1,247 non-FRI study controls were recruited. Increasing age [adjusted odds ratio (AOR) = 1.03; 95 % confidence interval (CI) = 1.01-1.05], recruit camp (AOR = 4.67; 95 % CI = 3.99-5.46) and smoker (AOR = 1.31; 95 % CI = 1.13-1.52) were independent risk factors of FRI. Malay ethnicity was positively associated with influenza A(H1N1)pdm09 (AOR = 1.50; 95 % CI = 1.04-2.15) and coxsackie/echovirus (AOR = 1.67; 95 % CI = 1.19-2.36) mono-infection. Significant contact risk factors were stay-out personnel with ill household member (AOR = 4.96; 95 % CI = 3.39-7.24), and stay-in personnel with ill bunkmate and household member (AOR = 3.55; 95 % CI = 2.57-4.91). Staying in camp with none ill in bunk and at home was a protective factor against FRI (AOR = 0.80; 95 % CI = 0.64-0.99). These contact risk factors were similarly observed for the five most common viruses detected, namely adenovirus, rhinoviruses, influenza A and B, and coxsackie/echovirus. CONCLUSION: Increasing age, smoker, recruit-camp, stay-out personnel with ill household members and stay-in personnel with ill bunkmates were independent risk factors of FRI in a semi-closed military environment. Early identification and isolation of ill personnel from their bunk may be effective to prevent and reduce transmission and disease burden.",2015 Jul 25,"['Pang, Junxiong', 'Jin, Jing', 'Loh, Jin Phang', 'Tan, Boon Huan', 'Koh, Wee Hong Victor', 'Ng, Sock Hoon', 'Ho, Zheng Jie Marc', 'Gao, Qiuhan', 'Cook, Alex R', 'Hsu, Li Yang', 'Lee, Vernon J', 'Chen, Mark I Cheng']",BMC Infect Dis,,,True
8da1231a64d73bc59f2af993bf1a2466265ffa4a,PMC,Phylogenetic and recombination analysis of Tobacco bushy top virus in China,http://dx.doi.org/10.1186/s12985-015-0340-2,PMC4514990,26209518,CC BY,"BACKGROUND: During the past decade, tobacco bushy top disease, which is mainly caused by a combination of Tobacco bushy top virus (TBTV) and Tobacco vein-distorting virus (TVDV), underwent a sudden appearance, extreme virulence and degeneration of the epidemic in the Yunnan province of China. In addition to integrative control of its aphid vector, it is of interest to examine diversity and evolution among different TBTV isolates. METHODS: 5’ and 3’ RACE, combined with one step full-length RT-PCR, were used to clone the full-length genome of three new isolates of TBTV that exhibited mild pathogenicity in Chinese fields. Nucleotide and amino acid sequences for the TBTV isolates were analyzed by DNAMAN. MEGA 5.0 was used to construct phylogenetic trees. RDP4 was used to detect recombination events during evolution of these isolates. RESULTS: The genomes of three isolates, termed TBTV-JC, TBTV-MD-I and TBTV-MD-II, were 4152 nt in length and included one distinctive difference from previously reported TBTV isolates: the first nucleotide of the genome was a guanylate instead of an adenylate. Diversity and phylogenetic analyses among these three new TBTV isolates and five other available isolates suggest that ORFs and 3’UTRs of TBTV may have evolved separately. Moreover, the RdRp-coding region was the most variable. Recombination analysis detected a total of 29 recombination events in the 8 TBTV isolates, in which 24 events are highly likely and 5 events have low-level likelihood based on their correlation with the phylogenetic trees. The three new TBTV isolates have individual recombination patterns with subtle divergences in parents and locations. CONCLUSIONS: The genome sizes of TBTV isolates were constant while different ORF-coding regions and 3’UTRs may have evolved separately. The RdRp-coding region was the most variable. Frequent recombination occurred among TBTV isolates. Three new TBTV isolates have individual recombination patterns and may have different progenitors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0340-2) contains supplementary material, which is available to authorized users.",2015 Jul 25,"['Wang, Deya', 'Yu, Chengming', 'Wang, Guolu', 'Shi, Kerong', 'Li, Fan', 'Yuan, Xuefeng']",Virol J,,,True
fb113c8235675412d874b092faf5b997ac410434,PMC,Acute phase proteins as local biomarkers of respiratory infection in calves,http://dx.doi.org/10.1186/s12917-015-0485-7,PMC4515006,26209015,CC BY,"BACKGROUND: Cumulating reports suggest that acute phase proteins (APPs) do not only play a role as systemic inflammatory mediators, but are also expressed in different tissues as local reaction to inflammatory stimuli. The present study aimed to evaluate presence and changes in luminal lung concentrations of the APPs haptoglobin (Hp), lipopolysaccharide binding protein (LBP), C-reactive protein (CRP), and lactoferrin (Lf) in calves with an acute respiratory disease experimentally induced by Chlamydia (C.) psittaci. RESULTS: Intra-bronchial inoculation of the pathogen resulted in a consistent respiratory illness. In venous blood of the infected calves (n = 13), concentrations of plasma proteins and serum LBP were assessed (i) before exposure and (ii) 8 times within 14 days after inoculation (dpi). Increasing clinical illness correlated significantly with increasing LBP—and decreasing albumin concentrations in blood, both verifying a systemic acute phase response. Broncho-alveolar lavage fluid (BALF) was obtained from all 13 calves experimentally infected with C. psittaci at 4, 9 and 14 dpi, and from 6 uninfected healthy calves. Concentrations of bovine serum albumin (BSA), Hp, LBP, CRP and Lf in BALF were determined by ELISA. In infected animals, absolute concentrations of LBP and Hp in BALF correlated significantly with the respiratory score. The quotient [LBP]/[BSA] in BALF peaked significantly in acutely infected animals (4 dpi), showed a time-dependent decrease during the recovery phase (9-14 dpi), and was significantly higher compared to healthy controls. Concentrations of Hp and Lf in BALF as well as [Hp]/[BSA]—and [Lf]/[BSA]-quotients decreased during the study in infected animals, but were never higher than in healthy controls. CRP concentrations and [CRP]/[BSA]-quotient did not express significant differences between infected and healthy animals or during the course of infection. CONCLUSION: In conclusion, absolute concentrations of LBP in blood and BALF as well as the quotient [LBP]/[BSA] in BALF perfectly paralleled the clinical course of respiratory illness after infection. Beside LBP, the suitability of Hp and Lf as local biomarkers of respiratory infections in cattle and their role in the local response to pathogens is worth further investigation, while CRP does not seem to play a role in local defense mechanisms of the bovine lung.",2015 Jul 25,"['Prohl, Annette', 'Schroedl, Wieland', 'Rhode, Heidrun', 'Reinhold, Petra']",BMC Vet Res,,,True
dbbb49ef360b3f97d6ecda042ef75186a78ddfa3,PMC,Risk assessment as a tool for improving external biosecurity at farm level,http://dx.doi.org/10.1186/s12917-015-0477-7,PMC4515931,26215281,CC BY,"BACKGROUND: Biosecurity routines at herd level may reduce the probability of introduction of disease into the herd, but some measures may be regarded as expensive and cumbersome for the farmers. Custom-made measures based on individual farm characteristics may aid in improving the actual application of on-farm biosecurity. The aim of the study was to provide a tool for calculating the effects of different biosecurity measures and strategies on the individual farm level. A simple model was developed to assess the risk of disease introduction and the need for biosecurity measures in individual farms. To illustrate the general applicability of the tool, it was applied to theoretical examples of Swedish cattle and pig farms and diseases endemic in those animal species in the EU, in two scenarios with different between-farm contact patterns. RESULTS: The model illustrated that the most important factors affecting the risk, and the effect of biosecurity measures such as quarantine routines and protective clothing, were the frequency of between-farm contacts and prevalence of the disease. The risk of introduction as well as the effect of biosecurity measures differed between farm types and disease transmission routes. Adapting contact patterns to mitigate a specific disease risk was as important as biosecurity measures for some farm types, but the largest effect was seen when combining biosecurity measures with more planned contact patterns. CONCLUSIONS: The risk assessment model proved useful for illustrating the risk of introduction of endemic diseases and the mitigating effect of different biosecurity measures on farm level. Model outputs could be used to justify prioritisation of measures or adapting contact patterns. The theoretic exercise of adjusting model inputs and comparing outputs may help veterinary advisors to understand farm-specific risks and motivate farmers to improve biosecurity in their individual farm, as it can be tailored to each farmer’s needs and preferences.",2015 Jul 28,"['Lewerin, Susanna Sternberg', 'Österberg, Julia', 'Alenius, Stefan', 'Elvander, Marianne', 'Fellström, Claes', 'Tråvén, Madeleine', 'Wallgren, Per', 'Waller, Karin Persson', 'Jacobson, Magdalena']",BMC Vet Res,,,True
6e94aa9c37dd7be5b553090717c59992005d114b,PMC,Identification of Glial Activation Markers by Comparison of Transcriptome Changes between Astrocytes and Microglia following Innate Immune Stimulation,http://dx.doi.org/10.1371/journal.pone.0127336,PMC4516330,26214311,CC0,"The activation of astrocytes and microglia is often associated with diseases of the central nervous system (CNS). Understanding how activation alters the transcriptome of these cells may offer valuable insight regarding how activation of these cells mediate neurological damage. Furthermore, identifying common and unique pathways of gene expression during activation may provide new insight into the distinct roles these cells have in the CNS during infection and inflammation. Since recent studies indicate that TLR7 recognizes not only viral RNA but also microRNAs that are released by damaged neurons and elevated during neurological diseases, we first examined the response of glial cells to TLR7 stimulation using microarray analysis. Microglia were found to generate a much stronger response to TLR7 activation than astrocytes, both in the number of genes induced as well as fold induction. Although the primary pathways induced by both cell types were directly linked to immune responses, microglia also induced pathways associated with cellular proliferation, while astrocytes did not. Targeted analysis of a subset of the upregulated genes identified unique mRNA, including Ifi202b which was only upregulated by microglia and was found to be induced during both retroviral and bunyavirus infections in the CNS. In addition, other genes including Birc3 and Gpr84 as well as two expressed sequences AW112010 and BC023105 were found to be induced in both microglia and astrocytes and were upregulated in the CNS following virus infection. Thus, expression of these genes may a useful measurement of glial activation during insult or injury to the CNS.",2015 Jul 27,"['Madeddu, Silvia', 'Woods, Tyson A.', 'Mukherjee, Piyali', 'Sturdevant, Dan', 'Butchi, Niranjan B.', 'Peterson, Karin E.']",PLoS One,,,True
ac1d4ff87c5d0b09e2b5a1e798c7c8ed4d8796cb,PMC,Identification of Glial Activation Markers by Comparison of Transcriptome Changes between Astrocytes and Microglia following Innate Immune Stimulation,http://dx.doi.org/10.1371/journal.pone.0127336,PMC4516330,26214311,CC0,"The activation of astrocytes and microglia is often associated with diseases of the central nervous system (CNS). Understanding how activation alters the transcriptome of these cells may offer valuable insight regarding how activation of these cells mediate neurological damage. Furthermore, identifying common and unique pathways of gene expression during activation may provide new insight into the distinct roles these cells have in the CNS during infection and inflammation. Since recent studies indicate that TLR7 recognizes not only viral RNA but also microRNAs that are released by damaged neurons and elevated during neurological diseases, we first examined the response of glial cells to TLR7 stimulation using microarray analysis. Microglia were found to generate a much stronger response to TLR7 activation than astrocytes, both in the number of genes induced as well as fold induction. Although the primary pathways induced by both cell types were directly linked to immune responses, microglia also induced pathways associated with cellular proliferation, while astrocytes did not. Targeted analysis of a subset of the upregulated genes identified unique mRNA, including Ifi202b which was only upregulated by microglia and was found to be induced during both retroviral and bunyavirus infections in the CNS. In addition, other genes including Birc3 and Gpr84 as well as two expressed sequences AW112010 and BC023105 were found to be induced in both microglia and astrocytes and were upregulated in the CNS following virus infection. Thus, expression of these genes may a useful measurement of glial activation during insult or injury to the CNS.",2015 Jul 27,"['Madeddu, Silvia', 'Woods, Tyson A.', 'Mukherjee, Piyali', 'Sturdevant, Dan', 'Butchi, Niranjan B.', 'Peterson, Karin E.']",PLoS One,,,False
d2057831023248265b009ed7fb7710123c69feaa,PMC,"Viroporins, Examples of the Two-Stage Membrane Protein Folding Model",http://dx.doi.org/10.3390/v7072781,PMC4517110,26131957,CC BY,"Viroporins are small, α-helical, hydrophobic virus encoded proteins, engineered to form homo-oligomeric hydrophilic pores in the host membrane. Viroporins participate in multiple steps of the viral life cycle, from entry to budding. As any other membrane protein, viroporins have to find the way to bury their hydrophobic regions into the lipid bilayer. Once within the membrane, the hydrophobic helices of viroporins interact with each other to form higher ordered structures required to correctly perform their porating activities. This two-step process resembles the two-stage model proposed for membrane protein folding by Engelman and Poppot. In this review we use the membrane protein folding model as a leading thread to analyze the mechanism and forces behind the membrane insertion and folding of viroporins. We start by describing the transmembrane segment architecture of viroporins, including the number and sequence characteristics of their membrane-spanning domains. Next, we connect the differences found among viroporin families to their viral genome organization, and finalize focusing on the pathways used by viroporins in their way to the membrane and on the transmembrane helix-helix interactions required to achieve proper folding and assembly.",2015 Jun 26,"['Martinez-Gil, Luis', 'Mingarro, Ismael']",Viruses,,,True
1986e96f2be6bd012fcd4d0b731caf62c7a4dea2,PMC,Relevance of Viroporin Ion Channel Activity on Viral Replication and Pathogenesis,http://dx.doi.org/10.3390/v7072786,PMC4517115,26151305,CC BY,"Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Viroporins interact with different cellular membranes and self-assemble forming ion conductive pores. In general, these channels display mild ion selectivity, and, eventually, membrane lipids play key structural and functional roles in the pore. Viroporins stimulate virus production through different mechanisms, and ion channel conductivity has been proved particularly relevant in several cases. Key stages of the viral cycle such as virus uncoating, transport and maturation are ion-influenced processes in many viral species. Besides boosting virus propagation, viroporins have also been associated with pathogenesis. Linking pathogenesis either to the ion conductivity or to other functions of viroporins has been elusive for a long time. This article summarizes novel pathways leading to disease stimulated by viroporin ion conduction, such as inflammasome driven immunopathology.",2015 Jul 3,"['Nieto-Torres, Jose L.', 'Verdiá-Báguena, Carmina', 'Castaño-Rodriguez, Carlos', 'Aguilella, Vicente M.', 'Enjuanes, Luis']",Viruses,,,True
ae3d16cad153ad376ec5782d74688a6f93093c37,PMC,Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses,http://dx.doi.org/10.3390/v7072794,PMC4517123,26198243,CC BY,"Interferon (IFN) treatment induces the expression of hundreds of IFN-stimulated genes (ISGs). However, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. IFNs inhibit rhabdovirus replication at different stages via the induction of a variety of ISGs. This review will discuss how individual ISG products confer resistance to rhabdoviruses by blocking viral entry, degrading single stranded viral RNA, inhibiting viral translation or preventing release of virions from the cell. Furthermore, this review will highlight how these viruses counteract the host IFN system.",2015 Jul 7,"['Blondel, Danielle', 'Maarifi, Ghizlane', 'Nisole, Sébastien', 'Chelbi-Alix, Mounira K.']",Viruses,,,True
adeed4609c727b1be5175cb36f7032a6337c89b3,PMC,Learning from Ebola Virus: How to Prevent Future Epidemics,http://dx.doi.org/10.3390/v7072797,PMC4517126,26184283,CC BY,"The recent Ebola virus disease (EVD) epidemic in Guinea, Liberia and Sierra Leone demonstrated that the World Health Organization (WHO) is incapable to control outbreaks of infectious diseases in less developed regions of the world. This essay analyses the causes for the failure of the international response and proposes four measures to improve resilience, early detection and response to future outbreaks of infectious diseases.",2015 Jul 9,"Kekulé, Alexander S.",Viruses,,,False
8e2bd29ae5f88af72cf04f8e7da51a3eb9c8258f,PMC,Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes,http://dx.doi.org/10.3390/v7072812,PMC4517141,26197333,CC BY,"Dengue virus (DENV) is an important human pathogen causing millions of disease cases and thousands of deaths worldwide. Non-structural protein 4A (NS4A) is a vital component of the viral replication complex (RC) and plays a major role in the formation of host cell membrane-derived structures that provide a scaffold for replication. The N-terminal cytoplasmic region of NS4A(1–48) is known to preferentially interact with highly curved membranes. Here, we provide experimental evidence for the stable binding of NS4A(1–48) to small liposomes using a liposome floatation assay and identify the lipid binding sequence by NMR spectroscopy. Mutations L6E;M10E were previously shown to inhibit DENV replication and to interfere with the binding of NS4A(1–48) to small liposomes. Our results provide new details on the interaction of the N-terminal region of NS4A with membranes and will prompt studies of the functional relevance of the curvature sensitive membrane anchor at the N-terminus of NS4A.",2015 Jul 21,"['Hung, Yu-Fu', 'Schwarten, Melanie', 'Hoffmann, Silke', 'Willbold, Dieter', 'Sklan, Ella H.', 'Koenig, Bernd W.']",Viruses,,,True
902feae616d8f0ffb508ef3a4a1fbc344bb63133,PMC,Antibody response of definitive hosts against antigens of two life stages of the neuropathogenic schistosome Trichobilharzia regenti,http://dx.doi.org/10.1186/s13071-015-1007-y,PMC4517386,26216102,CC BY,"BACKGROUND: The nasal avian schistosome Trichobilharzia regenti spends part of its intravertebrate period of life within the central nervous system. Migration of the parasites can be accompanied by neuromotor disorders or paralysis in natural definitive hosts (ducks) and even in laboratory mammals. Cercariae are also able to penetrate human skin and induce cercarial dermatitis. While the cellular and antibody responses against cercariae and migrating schistosomula have been investigated in mice, little is known about immune reactions in birds. This study first describes the dynamics of antibody response in infected ducks and identifies frequently recognized antigens that may serve as diagnostic markers of infection by T. regenti. METHODS: Groups of 35 domestic ducks and 10 mallards were exposed to different doses of T. regenti cercariae. Sera were collected at predefined time intervals and tested by ELISA for the presence of specific anti-cercarial IgY and IgM. Antigens recognized by the antibodies were identified on Western blots of cercariae and schistosomula. The applicability in immunodiagnostics was statistically evaluated by expression of specificity and sensitivity values for individual antigens. RESULTS: In ELISA, the levels of anti-cercarial IgM peaked on day 15 pi. Increased production of IgY associated with the later phases of infection was observed in most individuals around 20 dpi and culminated 30 dpi. The time course of antibody response did not differ among experimental groups, variations were only observed in the levels of specific IgY which depended rather on the age of ducks at the time of infection than on the infectious dose. On Western blots, 40 cercarial and 7 schistosomular antigens were recognized by IgY from infected ducks. Among them, 4 cercarial antigens of 50, 47, 32 and 19 kDa provided the most sensitive and specific reactions. CONCLUSIONS: Antigens of cercariae and schistosomula elicited distinct antibody response in ducks, which correlated positively with the age of animals at the time of infection. Several antigens originating in cercariae and fewer in schistosomula were recognized by IgY with diverse sensitivity and specificity; only a few seemed to be common to both stages. Four of them were considered as the most promising candidates for immunodiagnostics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-1007-y) contains supplementary material, which is available to authorized users.",2015 Jul 28,"['Turjanicová, Libuše', 'Mikeš, Libor', 'Pecková, Monika', 'Horák, Petr']",Parasit Vectors,,,True
b79e0dae232a80e5e92f12110cc4df835c171518,PMC,Representing virus-host interactions and other multi-organism processes in the Gene Ontology,http://dx.doi.org/10.1186/s12866-015-0481-x,PMC4517558,26215368,CC BY,"BACKGROUND: The Gene Ontology project is a collaborative effort to provide descriptions of gene products in a consistent and computable language, and in a species-independent manner. The Gene Ontology is designed to be applicable to all organisms but up to now has been largely under-utilized for prokaryotes and viruses, in part because of a lack of appropriate ontology terms. METHODS: To address this issue, we have developed a set of Gene Ontology classes that are applicable to microbes and their hosts, improving both coverage and quality in this area of the Gene Ontology. Describing microbial and viral gene products brings with it the additional challenge of capturing both the host and the microbe. Recognising this, we have worked closely with annotation groups to test and optimize the GO classes, and we describe here a set of annotation guidelines that allow the controlled description of two interacting organisms. CONCLUSIONS: Building on the microbial resources already in existence such as ViralZone, UniProtKB keywords and MeGO, this project provides an integrated ontology to describe interactions between microbial species and their hosts, with mappings to the external resources above. Housing this information within the freely-accessible Gene Ontology project allows the classes and annotation structure to be utilized by a large community of biologists and users.",2015 Jul 28,"['Foulger, R. E.', 'Osumi-Sutherland, D.', 'McIntosh, B. K.', 'Hulo, C.', 'Masson, P.', 'Poux, S.', 'Le Mercier, P.', 'Lomax, J.']",BMC Microbiol,,,True
e642816c09dd07b7bdf515088670a72ee8698bd8,PMC,Pulmonary Function and Clinical Manifestations of Patients Infected with Mild Influenza A Virus Subtype H1N1: A One-Year Follow-Up,http://dx.doi.org/10.1371/journal.pone.0133698,PMC4517883,26218647,CC BY,"OBJECTIVE: To investigate the long-term effects of mild H1N1 influenza infection on the pulmonary function of a cohort of patients. METHODS: Forty-eight patients, all diagnosed with influenza A virus subtype H1N1 in 2009, were retrospectively included in this study. Each patient in the study was monitored for 11-13 months by standard pulmonary function examination. The examination included monitoring respiratory tract infection symptoms (cough, expectoration or gasping) and vital signs. Long-term changes in symptoms and changes in vital signs were correlated back to and compared with the severity of the initial H1N1 influenza infection. RESULTS: One year post discharge, mild to moderate pulmonary dysfunction was observed in the majority of patients. Further, 54.2% of patients had signs of severe abnormal pulmonary function, including diffusion disorder (33.3%) and small airway dysfunction (33.3%). Fourteen patients presented with respiratory tract infection symptoms; 12 with abnormal pulmonary function and two with normal pulmonary function. Our results indicated that the change in pulmonary function at one year post discharge was not significantly correlated with the severity of H1N1 influenza. CONCLUSION: Signs and symptoms of abnormal pulmonary function accompanied by respiratory tract infection symptoms remain for some patients after one year following discharge from the hospital for mild influenza A virus subtype H1N1 infection. These patients should continue to be monitored for any changes in condition and symptoms and rehabilitation treatment should be provided when necessary.",2015 Jul 28,"['Liu, Wei', 'Peng, Liping', 'Liu, Hongmei', 'Hua, Shucheng']",PLoS One,,,True
f58cfab11be3906401550ffe0ba6e444d1056853,PMC,Human Enterovirus Nonstructural Protein 2C(ATPase) Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone,http://dx.doi.org/10.1371/journal.ppat.1005067,PMC4517893,26218680,CC BY,"RNA helicases and chaperones are the two major classes of RNA remodeling proteins, which function to remodel RNA structures and/or RNA-protein interactions, and are required for all aspects of RNA metabolism. Although some virus-encoded RNA helicases/chaperones have been predicted or identified, their RNA remodeling activities in vitro and functions in the viral life cycle remain largely elusive. Enteroviruses are a large group of positive-stranded RNA viruses in the Picornaviridae family, which includes numerous important human pathogens. Herein, we report that the nonstructural protein 2C(ATPase) of enterovirus 71 (EV71), which is the major causative pathogen of hand-foot-and-mouth disease and has been regarded as the most important neurotropic enterovirus after poliovirus eradication, functions not only as an RNA helicase that 3′-to-5′ unwinds RNA helices in an adenosine triphosphate (ATP)-dependent manner, but also as an RNA chaperone that destabilizes helices bidirectionally and facilitates strand annealing and complex RNA structure formation independently of ATP. We also determined that the helicase activity is based on the EV71 2C(ATPase) middle domain, whereas the C-terminus is indispensable for its RNA chaperoning activity. By promoting RNA template recycling, 2C(ATPase) facilitated EV71 RNA synthesis in vitro; when 2C(ATPase) helicase activity was impaired, EV71 RNA replication and virion production were mostly abolished in cells, indicating that 2C(ATPase)-mediated RNA remodeling plays a critical role in the enteroviral life cycle. Furthermore, the RNA helicase and chaperoning activities of 2C(ATPase) are also conserved in coxsackie A virus 16 (CAV16), another important enterovirus. Altogether, our findings are the first to demonstrate the RNA helicase and chaperoning activities associated with enterovirus 2C(ATPase), and our study provides both in vitro and cellular evidence for their potential roles during viral RNA replication. These findings increase our understanding of enteroviruses and the two types of RNA remodeling activities.",2015 Jul 28,"['Xia, Hongjie', 'Wang, Peipei', 'Wang, Guang-Chuan', 'Yang, Jie', 'Sun, Xianlin', 'Wu, Wenzhe', 'Qiu, Yang', 'Shu, Ting', 'Zhao, Xiaolu', 'Yin, Lei', 'Qin, Cheng-Feng', 'Hu, Yuanyang', 'Zhou, Xi']",PLoS Pathog,,,True
2cd037e5b6e8f285b0a68b5d10c627d407046c0e,PMC,Ebola Virus Disease: Experience and Decision Making for the First Patients outside of Africa,http://dx.doi.org/10.1371/journal.pmed.1001857,PMC4517924,26218574,CC BY,David Stephens and colleagues describe their experience of treating patients with Ebola virus disease at Emory University in the United States.,2015 Jul 28,"['Stephens, David S.', 'Ribner, Bruce S.', 'Gartland, Bryce D.', 'Feistritzer, Nancye R.', 'Farley, Monica M.', 'Larsen, Christian P.', 'Fox, John T.']",PLoS Med,,,True
0d1d976e7073e6c1bbc69805f5c61a2f8607c911,PMC,Inhibitory effect of Phyllanthus urinaria L. extract on the replication of lamivudine-resistant hepatitis B virus in vitro,http://dx.doi.org/10.1186/s12906-015-0792-3,PMC4518506,26220282,CC BY,"BACKGROUND: Long-term treatment of chronic hepatitis B (CHB) with nucleos(t)ide analogs results in the emergence of drug-resistant hepatitis B virus (HBV) harboring mutations in the polymerase (P) gene. The Phyllanthus extract has anti-HBV activity; however, its antiviral activity against lamivudine (LMV)-resistant mutants has not been examined. METHODS: HBV harboring LMV-resistant mutations (rtM204I, rtM204V, and rtM204S) in the P gene at the YMDD ((203)tyrosine-methionine-aspartate-aspartate(206)) reverse transcriptase (RT) active site were generated and their sensitivity to Phyllanthus urinaria koreanis extract examined. Southern blotting and real-time PCR were used to determine the concentration of plant extract required to inhibit HBV DNA synthesis by 50 and 90 % (EC(50) and EC(90), respectively). An enzyme-linked immunosorbent assay was used to measure the EC(50) of HBV surface antigen (HBsAg) and HBV core antigen (HBcAg) secretion, and the 50 % cytotoxic concentration of the extract was measured in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Real-time RT-PCR was used to measure mRNA expression levels. RESULTS: The expression of intracellular HBV DNAs in HBV WT- or mutant-transfected HepG2 cells decreased upon treatment with Phyllanthus extract. The secretion of HBsAg and HBcAg also fell in a dose-dependent manner. Phyllanthus extract induced interferon-beta (IFN-β), cyclooxygenase-2 (COX-2), and interleukin-6 (IL-6) mRNA expression in HBV WT-transfected HepG2 cells, possibly via activation of extracellular signal-regulated kinases and c-jun N-terminal kinases and the induction of retinoic acid inducible gene-I, toll-like receptor 3, myeloid differentiation primary response gene 88, and/or tumor necrosis factor receptor-associated factor 6 gene expression. HBV transfection in the absence of extract or exposure of cells to extract alone did not trigger these signaling cascades. CONCLUSIONS: Phyllanthus extract inhibited HBV DNA synthesis and HBsAg and HBcAg secretion by replicating cells harboring HBV wild-type and LMV-resistant mutants, likely by inducing the expression of IFN-β, COX-2, and IL-6. These data indicate that Phyllanthus extract may be useful as an alternative therapeutic agent for the treatment of drug-resistant CHB patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12906-015-0792-3) contains supplementary material, which is available to authorized users.",2015 Jul 29,"['Jung, Jaesung', 'Kim, Nam Keun', 'Park, Sun', 'Shin, Ho-Joon', 'Hwang, Seong Gyu', 'Kim, Kyongmin']",BMC Complement Altern Med,,,True
d37ad55db18a412c55ca07e3780ab65ec8040908,PMC,"An Overview of Practical Applications of Protein Disorder Prediction and Drive for Faster, More Accurate Predictions",http://dx.doi.org/10.3390/ijms160715384,PMC4519904,26198229,CC BY,"Protein disordered regions are segments of a protein chain that do not adopt a stable structure. Thus far, a variety of protein disorder prediction methods have been developed and have been widely used, not only in traditional bioinformatics domains, including protein structure prediction, protein structure determination and function annotation, but also in many other biomedical fields. The relationship between intrinsically-disordered proteins and some human diseases has played a significant role in disorder prediction in disease identification and epidemiological investigations. Disordered proteins can also serve as potential targets for drug discovery with an emphasis on the disordered-to-ordered transition in the disordered binding regions, and this has led to substantial research in drug discovery or design based on protein disordered region prediction. Furthermore, protein disorder prediction has also been applied to healthcare by predicting the disease risk of mutations in patients and studying the mechanistic basis of diseases. As the applications of disorder prediction increase, so too does the need to make quick and accurate predictions. To fill this need, we also present a new approach to predict protein residue disorder using wide sequence windows that is applicable on the genomic scale.",2015 Jul 7,"['Deng, Xin', 'Gumm, Jordan', 'Karki, Suman', 'Eickholt, Jesse', 'Cheng, Jianlin']",Int J Mol Sci,,,True
30d069a3931b607b8f5c3b7b2556e78f2cd9b4e3,PMC,The CCR5Δ32 (rs333) polymorphism is not a predisposing factor for severe pandemic influenza in the Brazilian admixed population,http://dx.doi.org/10.1186/s13104-015-1299-1,PMC4520097,26223981,CC BY,"BACKGROUND: Recent studies have tried to identify host genetic variants that could explain severe cases and deaths in infection with Influenza A(H1N1)pdm09, especially among children and young adults. CCR5 is a chemokine receptor expressed on T cells, macrophages and dendritic cells, which is an important mediator of leukocyte chemotaxis during the immune response. A deletion mutation (Δ32) in this gene interferes with the response of immune cells, impairing viral clearance. We evaluated the CCR5Δ32 polymorphism (rs333) in individuals of the Brazilian admixed population with a diagnosis of Influenza A(H1N1)pdm09 infection. METHODS: A total of 330 subjects with a diagnosis of Influenza A(H1N1)pdm09, evaluated at health services in the northern and northeastern regions of Brazil between June 2009 and August 2010, were genotyped for the Δ32 deletion (rs333). The cases were classified according to the progression of infection into a group of hospitalized patients (n = 156) and a group of non-hospitalized patients (n = 174). RESULTS: No significant differences in the allele or genotype frequencies of the CCR5Δ32 polymorphism were observed between non-hospitalized and hospitalized patients (p = 0.289 and p = 0.431, respectively). CONCLUSION: The Δ32 deletion in the CCR5 gene is not associated with an unfavorable outcome in patients infected with Influenza A(H1N1)pdm09 in the Brazilian admixed population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13104-015-1299-1) contains supplementary material, which is available to authorized users.",2015 Jul 30,"['Maestri, Alvino', 'dos Santos, Mirleide Cordeiro', 'Ribeiro-Rodrigues, Elzemar M', 'de Mello, Wyller Alencar', 'Sousa, Rita Catarina Medeiros', 'dos Santos, Sidney Emanuel', 'Sortica, Vinicius Albuquerque']",BMC Res Notes,,,False
1f16c5e424d5b436085329d94649118ac319e748,PMC,The CCR5Δ32 (rs333) polymorphism is not a predisposing factor for severe pandemic influenza in the Brazilian admixed population,http://dx.doi.org/10.1186/s13104-015-1299-1,PMC4520097,26223981,CC BY,"BACKGROUND: Recent studies have tried to identify host genetic variants that could explain severe cases and deaths in infection with Influenza A(H1N1)pdm09, especially among children and young adults. CCR5 is a chemokine receptor expressed on T cells, macrophages and dendritic cells, which is an important mediator of leukocyte chemotaxis during the immune response. A deletion mutation (Δ32) in this gene interferes with the response of immune cells, impairing viral clearance. We evaluated the CCR5Δ32 polymorphism (rs333) in individuals of the Brazilian admixed population with a diagnosis of Influenza A(H1N1)pdm09 infection. METHODS: A total of 330 subjects with a diagnosis of Influenza A(H1N1)pdm09, evaluated at health services in the northern and northeastern regions of Brazil between June 2009 and August 2010, were genotyped for the Δ32 deletion (rs333). The cases were classified according to the progression of infection into a group of hospitalized patients (n = 156) and a group of non-hospitalized patients (n = 174). RESULTS: No significant differences in the allele or genotype frequencies of the CCR5Δ32 polymorphism were observed between non-hospitalized and hospitalized patients (p = 0.289 and p = 0.431, respectively). CONCLUSION: The Δ32 deletion in the CCR5 gene is not associated with an unfavorable outcome in patients infected with Influenza A(H1N1)pdm09 in the Brazilian admixed population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13104-015-1299-1) contains supplementary material, which is available to authorized users.",2015 Jul 30,"['Maestri, Alvino', 'dos Santos, Mirleide Cordeiro', 'Ribeiro-Rodrigues, Elzemar M', 'de Mello, Wyller Alencar', 'Sousa, Rita Catarina Medeiros', 'dos Santos, Sidney Emanuel', 'Sortica, Vinicius Albuquerque']",BMC Res Notes,,,False
87e6ba2c7e5748b172c7530dbb9e8a040e74a719,PMC,The CCR5Δ32 (rs333) polymorphism is not a predisposing factor for severe pandemic influenza in the Brazilian admixed population,http://dx.doi.org/10.1186/s13104-015-1299-1,PMC4520097,26223981,CC BY,"BACKGROUND: Recent studies have tried to identify host genetic variants that could explain severe cases and deaths in infection with Influenza A(H1N1)pdm09, especially among children and young adults. CCR5 is a chemokine receptor expressed on T cells, macrophages and dendritic cells, which is an important mediator of leukocyte chemotaxis during the immune response. A deletion mutation (Δ32) in this gene interferes with the response of immune cells, impairing viral clearance. We evaluated the CCR5Δ32 polymorphism (rs333) in individuals of the Brazilian admixed population with a diagnosis of Influenza A(H1N1)pdm09 infection. METHODS: A total of 330 subjects with a diagnosis of Influenza A(H1N1)pdm09, evaluated at health services in the northern and northeastern regions of Brazil between June 2009 and August 2010, were genotyped for the Δ32 deletion (rs333). The cases were classified according to the progression of infection into a group of hospitalized patients (n = 156) and a group of non-hospitalized patients (n = 174). RESULTS: No significant differences in the allele or genotype frequencies of the CCR5Δ32 polymorphism were observed between non-hospitalized and hospitalized patients (p = 0.289 and p = 0.431, respectively). CONCLUSION: The Δ32 deletion in the CCR5 gene is not associated with an unfavorable outcome in patients infected with Influenza A(H1N1)pdm09 in the Brazilian admixed population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13104-015-1299-1) contains supplementary material, which is available to authorized users.",2015 Jul 30,"['Maestri, Alvino', 'dos Santos, Mirleide Cordeiro', 'Ribeiro-Rodrigues, Elzemar M', 'de Mello, Wyller Alencar', 'Sousa, Rita Catarina Medeiros', 'dos Santos, Sidney Emanuel', 'Sortica, Vinicius Albuquerque']",BMC Res Notes,,,True
e6a4aa79206219f2e1229c6ecc507078520466b0,PMC,Membrane-Active Sequences within gp41 Membrane Proximal External Region (MPER) Modulate MPER-Containing Peptidyl Fusion Inhibitor Activity and the Biosynthesis of HIV-1 Structural Proteins,http://dx.doi.org/10.1371/journal.pone.0134851,PMC4521866,26230322,CC BY,"The membrane proximal external region (MPER) is a highly conserved membrane-active region located at the juxtamembrane positions within class I viral fusion glycoproteins and essential for membrane fusion events during viral entry. The MPER in the human immunodeficiency virus type I (HIV-1) envelope protein (Env) interacts with the lipid bilayers through a cluster of tryptophan (Trp) residues and a C-terminal cholesterol-interacting motif. The inclusion of the MPER N-terminal sequence contributes to the membrane reactivity and anti-viral efficacy of the first two anti-HIV peptidyl fusion inhibitors T20 and T1249. As a type I transmembrane protein, Env also interacts with the cellular membranes during its biosynthesis and trafficking. Here we investigated the roles of MPER membrane-active sequences during both viral entry and assembly, specifically, their roles in the design of peptidyl fusion inhibitors and the biosynthesis of viral structural proteins. We found that elimination of the membrane-active elements in MPER peptides, namely, penta Trp→alanine (Ala) substitutions and the disruption of the C-terminal cholesterol-interacting motif through deletion inhibited the anti-viral effect against the pseudotyped HIV-1. Furthermore, as compared to C-terminal dimerization, N-terminal dimerization of MPER peptides and N-terminal extension with five helix-forming residues enhanced their anti-viral efficacy substantially. The secondary structure study revealed that the penta-Trp→Ala substitutions also increased the helical content in the MPER sequence, which prompted us to study the biological relevance of such mutations in pre-fusion Env. We observed that Ala mutations of Trp664, Trp668 and Trp670 in MPER moderately lowered the intracellular and intraviral contents of Env while significantly elevating the content of another viral structural protein, p55/Gag and its derivative p24/capsid. The data suggest a role of the gp41 MPER in the membrane-reactive events during both viral entry and budding, and provide insights into the future development of anti-viral therapeutics.",2015 Jul 31,"['Zhang, Si Min', 'Jejcic, Alenka', 'Tam, James P.', 'Vahlne, Anders']",PLoS One,,,True
d78b99436685b3f545dedc32f1166776b916abd6,PMC,"Development of an indirect ELISA, blocking ELISA, fluorescent microsphere immunoassay and fluorescent focus neutralization assay for serologic evaluation of exposure to North American strains of Porcine Epidemic Diarrhea Virus",http://dx.doi.org/10.1186/s12917-015-0500-z,PMC4522128,26232106,CC BY,"BACKGROUND: Recent, severe outbreaks of porcine epidemic diarrhea virus (PEDV) in Asia and North America highlight the need for well-validated diagnostic tests for the identification of PEDV infected animals and evaluation of their immune status to this virus. PEDV was first detected in the U.S. in May 2013 and spread rapidly across the country. Some serological assays for PEDV have been previously described, but few were readily available in the U.S. Several U.S. laboratories quickly developed indirect fluorescent antibody (IFA) assays for the detection of antibodies to PEDV in swine serum, indicating prior exposure. However, the IFA has several disadvantages, including low throughput and relatively subjective interpretation. Different serologic test formats have advantages and disadvantages, depending on the questions being asked, so a full repertoire of tests is useful. Therefore, the objective of this study was to develop and validate multiple improved serological assays for PEDV, including an indirect ELISA (iELISA); a highly specific monoclonal antibody-based blocking ELISA (bELISA); fluorescent microsphere immunoassays (FMIA) that can be multiplexed to monitor exposure to multiple antigens and pathogens simultaneously; and a fluorescent focus neutralization assay (FFN) to measure functional virus neutralizing antibodies. RESULTS: A recombinant North American nucleoprotein (NP) based iELISA was developed and validated along with a bELISA using newly developed PEDV-NP specific biotinylated monoclonal antibodies (mAbs) and an FMIA using magnetic beads coupled with expressed NA PEDV-NP. Receiver operating characteristic (ROC) analysis was performed using swine serum samples (iELISA n = 1486, bELISA n = 1186, FMIA n = 1420). The ROC analysis for the FMIA showed estimated sensitivity and specificity of 98.2 and 99.2 %, respectively. The iELISA and bELISA showed a sensitivity and specificity of 97.9 and 97.6 %; and 98.2 and 98.9 %, respectively. Inter-rater (kappa) agreement was calculated to be 0.941 between iELISA and IFA, 0.945 between bELISA and IFA and 0.932 between FMIA and IFA. Similar comparative kappa values were observed between the iELISA, bELISA and FMIA, which demonstrated a significant level of testing agreement among the three assays. No cross-reactivity with the closely related coronaviruses, transmissible gastroenteritis virus (TGEV) or porcine respiratory coronavirus (PRCV) was noted with these assays. All three assays detected seroconversion of naïve animals within 6–9 days post exposure. The FFN assay allows relative quantitation of functional neutralizing antibodies in serum, milk or colostrum samples. CONCLUSION: Well-validated iELISA, bELISA and FMIA assays for the detection of PEDV antibodies were developed and showed good correlation with IFA and each other. Each assay format has advantages that dictate how they will be used in the field. Newly developed mAbs to the PEDV-NP were used in the bELISA and for expediting FFN testing in the detection and quantitation of neutralizing antibodies. In addition, these PEDV mAbs are useful for immunohistochemistry, fluorescent antibody staining and other antigen-based tests. Measurement of neutralizing antibody responses using the FFN assay may provide a valuable tool for assessment of vaccine candidates or protective immunity.",2015 Aug 1,"['Okda, Faten', 'Liu, Xiaodong', 'Singrey, Aaron', 'Clement, Travis', 'Nelson, Julie', 'Christopher-Hennings, Jane', 'Nelson, Eric A.', 'Lawson, Steven']",BMC Vet Res,,,True
9efdb1c8ae8a36d1b0bd0dac741d0de23df2ac9e,PMC,Cytokine systems approach demonstrates differences in innate and pro-inflammatory host responses between genetically distinct MERS-CoV isolates,http://dx.doi.org/10.1186/1471-2164-15-1161,PMC4522970,25534508,CC BY,"BACKGROUND: The recent emergence of a novel coronavirus in the Middle East (designated MERS-CoV) is a reminder of the zoonotic and pathogenic potential of emerging coronaviruses in humans. Clinical features of Middle East respiratory syndrome (MERS) include atypical pneumonia and progressive respiratory failure that is highly reminiscent of severe acute respiratory syndrome (SARS) caused by SARS-CoV. The host response is a key component of highly pathogenic respiratory virus infection. Here, we computationally analyzed gene expression changes in a human airway epithelial cell line infected with two genetically distinct MERS-CoV strains obtained from human patients, MERS-CoV SA 1 and MERS-CoV Eng 1. RESULTS: Using topological techniques, including persistence homology and filtered clustering, we performed a comparative transcriptional analysis of human Calu-3 cell host responses to the different MERS-CoV strains, with MERS-CoV Eng 1 inducing early kinetic changes, between 3 and 12 hours post infection, compared to MERS-CoV SA 1. Robust transcriptional changes distinguished the two MERS-CoV strains predominantly at the late time points. Combining statistical analysis of infection and cytokine-stimulated Calu-3 transcriptomics, we identified differential innate responses, including up-regulation of extracellular remodeling genes following MERS-CoV Eng 1 infection and differential pro-inflammatory responses. CONCLUSIONS: Through our genomics-based approach, we found topological differences in the kinetics and magnitude of the host response to MERS-CoV SA 1 and MERS-CoV Eng 1, with differential expression of innate immune and pro-inflammatory responsive genes as a result of IFN, TNF and IL-1α signaling. Predicted activation for STAT3 mediating gene expression relevant for epithelial cell-to-cell adherens and junction signaling in MERS-CoV Eng 1 infection suggest that these transcriptional differences may be the result of amino acid differences in viral proteins known to modulate innate immunity during MERS-CoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1161) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Selinger, Christian', 'Tisoncik-Go, Jennifer', 'Menachery, Vineet D', 'Agnihothram, Sudhakar', 'Law, G Lynn', 'Chang, Jean', 'Kelly, Sara M', 'Sova, Pavel', 'Baric, Ralph S', 'Katze, Michael G']",BMC Genomics,,,False
a13166feda1f37450932faf548a882c927840ea1,PMC,Cytokine systems approach demonstrates differences in innate and pro-inflammatory host responses between genetically distinct MERS-CoV isolates,http://dx.doi.org/10.1186/1471-2164-15-1161,PMC4522970,25534508,CC BY,"BACKGROUND: The recent emergence of a novel coronavirus in the Middle East (designated MERS-CoV) is a reminder of the zoonotic and pathogenic potential of emerging coronaviruses in humans. Clinical features of Middle East respiratory syndrome (MERS) include atypical pneumonia and progressive respiratory failure that is highly reminiscent of severe acute respiratory syndrome (SARS) caused by SARS-CoV. The host response is a key component of highly pathogenic respiratory virus infection. Here, we computationally analyzed gene expression changes in a human airway epithelial cell line infected with two genetically distinct MERS-CoV strains obtained from human patients, MERS-CoV SA 1 and MERS-CoV Eng 1. RESULTS: Using topological techniques, including persistence homology and filtered clustering, we performed a comparative transcriptional analysis of human Calu-3 cell host responses to the different MERS-CoV strains, with MERS-CoV Eng 1 inducing early kinetic changes, between 3 and 12 hours post infection, compared to MERS-CoV SA 1. Robust transcriptional changes distinguished the two MERS-CoV strains predominantly at the late time points. Combining statistical analysis of infection and cytokine-stimulated Calu-3 transcriptomics, we identified differential innate responses, including up-regulation of extracellular remodeling genes following MERS-CoV Eng 1 infection and differential pro-inflammatory responses. CONCLUSIONS: Through our genomics-based approach, we found topological differences in the kinetics and magnitude of the host response to MERS-CoV SA 1 and MERS-CoV Eng 1, with differential expression of innate immune and pro-inflammatory responsive genes as a result of IFN, TNF and IL-1α signaling. Predicted activation for STAT3 mediating gene expression relevant for epithelial cell-to-cell adherens and junction signaling in MERS-CoV Eng 1 infection suggest that these transcriptional differences may be the result of amino acid differences in viral proteins known to modulate innate immunity during MERS-CoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1161) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Selinger, Christian', 'Tisoncik-Go, Jennifer', 'Menachery, Vineet D', 'Agnihothram, Sudhakar', 'Law, G Lynn', 'Chang, Jean', 'Kelly, Sara M', 'Sova, Pavel', 'Baric, Ralph S', 'Katze, Michael G']",BMC Genomics,,,False
49471df378964515ebc4e4f35f1248d84ac7d626,PMC,Cytokine systems approach demonstrates differences in innate and pro-inflammatory host responses between genetically distinct MERS-CoV isolates,http://dx.doi.org/10.1186/1471-2164-15-1161,PMC4522970,25534508,CC BY,"BACKGROUND: The recent emergence of a novel coronavirus in the Middle East (designated MERS-CoV) is a reminder of the zoonotic and pathogenic potential of emerging coronaviruses in humans. Clinical features of Middle East respiratory syndrome (MERS) include atypical pneumonia and progressive respiratory failure that is highly reminiscent of severe acute respiratory syndrome (SARS) caused by SARS-CoV. The host response is a key component of highly pathogenic respiratory virus infection. Here, we computationally analyzed gene expression changes in a human airway epithelial cell line infected with two genetically distinct MERS-CoV strains obtained from human patients, MERS-CoV SA 1 and MERS-CoV Eng 1. RESULTS: Using topological techniques, including persistence homology and filtered clustering, we performed a comparative transcriptional analysis of human Calu-3 cell host responses to the different MERS-CoV strains, with MERS-CoV Eng 1 inducing early kinetic changes, between 3 and 12 hours post infection, compared to MERS-CoV SA 1. Robust transcriptional changes distinguished the two MERS-CoV strains predominantly at the late time points. Combining statistical analysis of infection and cytokine-stimulated Calu-3 transcriptomics, we identified differential innate responses, including up-regulation of extracellular remodeling genes following MERS-CoV Eng 1 infection and differential pro-inflammatory responses. CONCLUSIONS: Through our genomics-based approach, we found topological differences in the kinetics and magnitude of the host response to MERS-CoV SA 1 and MERS-CoV Eng 1, with differential expression of innate immune and pro-inflammatory responsive genes as a result of IFN, TNF and IL-1α signaling. Predicted activation for STAT3 mediating gene expression relevant for epithelial cell-to-cell adherens and junction signaling in MERS-CoV Eng 1 infection suggest that these transcriptional differences may be the result of amino acid differences in viral proteins known to modulate innate immunity during MERS-CoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1161) contains supplementary material, which is available to authorized users.",2014 Dec 22,"['Selinger, Christian', 'Tisoncik-Go, Jennifer', 'Menachery, Vineet D', 'Agnihothram, Sudhakar', 'Law, G Lynn', 'Chang, Jean', 'Kelly, Sara M', 'Sova, Pavel', 'Baric, Ralph S', 'Katze, Michael G']",BMC Genomics,,,True
1db4560940a913194230a37755d10fa154b09d15,PMC,A comparative analysis of host responses to avian influenza infection in ducks and chickens highlights a role for the interferon-induced transmembrane proteins in viral resistance,http://dx.doi.org/10.1186/s12864-015-1778-8,PMC4523026,26238195,CC BY,"BACKGROUND: Chickens are susceptible to infection with a limited number of Influenza A viruses and are a potential source of a human influenza pandemic. In particular, H5 and H7 haemagglutinin subtypes can evolve from low to highly pathogenic strains in gallinaceous poultry. Ducks on the other hand are a natural reservoir for these viruses and are able to withstand most avian influenza strains. RESULTS: Transcriptomic sequencing of lung and ileum tissue samples from birds infected with high (H5N1) and low (H5N2) pathogenic influenza viruses has allowed us to compare the early host response to these infections in both these species. Chickens (but not ducks) lack the intracellular receptor for viral ssRNA, RIG-I and the gene for an important RIG-I binding protein, RNF135. These differences in gene content partly explain the differences in host responses to low pathogenic and highly pathogenic avian influenza virus in chicken and ducks. We reveal very different patterns of expression of members of the interferon-induced transmembrane protein (IFITM) gene family in ducks and chickens. In ducks, IFITM1, 2 and 3 are strongly up regulated in response to highly pathogenic avian influenza, where little response is seen in chickens. Clustering of gene expression profiles suggests IFITM1 and 2 have an anti-viral response and IFITM3 may restrict avian influenza virus through cell membrane fusion. We also show, through molecular phylogenetic analyses, that avian IFITM1 and IFITM3 genes have been subject to both episodic and pervasive positive selection at specific codons. In particular, avian IFITM1 showed evidence of positive selection in the duck lineage at sites known to restrict influenza virus infection. CONCLUSIONS: Taken together these results support a model where the IFITM123 protein family and RIG-I all play a crucial role in the tolerance of ducks to highly pathogenic and low pathogenic strains of avian influenza viruses when compared to the chicken. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1778-8) contains supplementary material, which is available to authorized users.",2015 Aug 4,"['Smith, Jacqueline', 'Smith, Nikki', 'Yu, Le', 'Paton, Ian R.', 'Gutowska, Maria Weronika', 'Forrest, Heather L.', 'Danner, Angela F.', 'Seiler, J. Patrick', 'Digard, Paul', 'Webster, Robert G.', 'Burt, David W.']",BMC Genomics,,,True
8d6ac4365bc4ab3f85ea3a5c287cddfaef482707,PMC,Comparison of Infectious Agents Susceptibility to Photocatalytic Effects of Nanosized Titanium and Zinc Oxides: A Practical Approach,http://dx.doi.org/10.1186/s11671-015-1023-z,PMC4523504,26239879,CC BY,"Nanotechnology contributes towards a more effective eradication of pathogens that have emerged in hospitals, veterinary clinics, and food processing plants and that are resistant to traditional drugs or disinfectants. Since new methods of pathogens eradication must be invented and implemented, nanotechnology seems to have become the response to that acute need. A remarkable achievement in this field of science was the creation of self-disinfecting surfaces that base on advanced oxidation processes (AOPs). Thus, the phenomenon of photocatalysis was practically applied. Among the AOPs that have been most studied in respect of their ability to eradicate viruses, prions, bacteria, yeasts, and molds, there are the processes of TiO(2)/UV and ZnO/UV. Titanium dioxide (TiO(2)) and zinc oxide (ZnO) act as photocatalysts, after they have been powdered to nanoparticles. Ultraviolet (UV) radiation is an agent that determines their excitation. Methods using photocatalytic properties of nanosized TiO(2) and ZnO prove to be highly efficient in inactivation of infectious agents. Therefore, they are being applied on a growing scale. AOP-based disinfection is regarded as a very promising tool that might help overcome problems in food hygiene and public health protection. The susceptibility of infectious agents to photocatalylic processes can be generally arranged in the following order: viruses > prions > Gram-negative bacteria > Gram-positive bacteria > yeasts > molds.",2015 Aug 4,"['Bogdan, Janusz', 'Zarzyńska, Joanna', 'Pławińska-Czarnak, Joanna']",Nanoscale Res Lett,,,True
d6ea3039fed0942c355cabc8a67f7226cd05fc8c,PMC,"IFN-β-inducing, unusual viral RNA species produced by paramyxovirus infection accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner",http://dx.doi.org/10.3389/fmicb.2015.00804,PMC4523817,26300870,CC BY,"The interferon (IFN) system is one of the most important defensive responses of mammals against viruses, and is rapidly evoked when the pathogen-associated molecular patterns (PAMPs) of viruses are sensed. Non-self, virus-derived RNA species have been identified as the PAMPs of RNA viruses. In the present study, we compared different types of IFN-β-inducing and -non-inducing viruses in the context of Sendai virus infection. We found that some types of unusual viral RNA species were produced by infections with IFN-β-inducing viruses and accumulated into distinct cytoplasmic structures in an RNA-type-dependent manner. One of these structures was similar to the so-called antiviral stress granules (avSGs) formed by an infection with IFN-inducing viruses whose C proteins were knocked-out or mutated. Non-encapsidated, unusual viral RNA harboring the 5′-terminal region of the viral genome as well as RIG-I and typical SG markers accumulated in these granules. Another was a non-SG-like inclusion formed by an infection with the Cantell strain; a copyback-type DI genome, but not an authentic viral genome, specifically accumulated in the inclusion, whereas RIG-I and SG markers did not. The induction of IFN-β was closely associated with the production of these unusual RNAs as well as the formation of the cytoplasmic structures.",2015 Aug 4,"['Yoshida, Asuka', 'Kawabata, Ryoko', 'Honda, Tomoyuki', 'Tomonaga, Keizo', 'Sakaguchi, Takemasa', 'Irie, Takashi']",Front Microbiol,,,True
f00f183d0bce0091a02349ec1eab44a76dad9bc4,PMC,"Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold",http://dx.doi.org/10.3389/fmicb.2015.00755,PMC4523942,26300850,CC BY,"For the past 25 years, phage display technology has been an invaluable tool for studies of protein–protein interactions. However, the inherent biological, biochemical, and biophysical properties of filamentous bacteriophage, as well as the ease of its genetic manipulation, also make it an attractive platform outside the traditional phage display canon. This review will focus on the unique properties of the filamentous bacteriophage and highlight its diverse applications in current research. Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage’s potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage’s large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. Despite their ubiquity in the biosphere, metagenomics work is just beginning to explore the ecology of filamentous and non-filamentous phage, and their role in the evolution of bacterial populations. Thus, the filamentous phage represents a robust, inexpensive, and versatile microorganism whose bioengineering applications continue to expand in new directions, although its limitations in some spheres impose obstacles to its widespread adoption and use.",2015 Aug 4,"['Henry, Kevin A.', 'Arbabi-Ghahroudi, Mehdi', 'Scott, Jamie K.']",Front Microbiol,,,True
b62ce73d8d2c9e794c96ce0be7d52ed55b87fa52,PMC,Application of recombinant severe fever with thrombocytopenia syndrome virus nucleocapsid protein for the detection of SFTSV-specific human IgG and IgM antibodies by indirect ELISA,http://dx.doi.org/10.1186/s12985-015-0350-0,PMC4524020,26239826,CC BY,"BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that was first reported in China in 2011. It is caused by SFTS virus (SFTSV) which is a member of the Phlebovirus genus in the Bunyaviridae family. SFTSV has been classified as a BSL3 pathogen. There is a need to develop safe and affordable serodiagnostic methods for proper clinical management of infected patients. METHODS: The full length nucleocapsid (N) gene of SFTSV Yamaguchi strain was amplified by RT-PCR and cloned to an expression vector pQE30. The recombinant (r) SFTSV-N protein was expressed by using Escherichia coli (E. coli) expression system and purified under native conditions. rSFTSV-N protein based indirect IgG and IgM enzyme linked immunosorbent assay (ELISA) systems were established to detect specific human IgG and IgM antibodies, respectively. One hundred fifteen serum samples from clinically suspected-SFTS patients were used to evaluate the newly established systems and the results were compared with the total antibody detecting sandwich ELISA system. RESULTS: The native form of recombinant (r) SFTSV-N protein was expressed and purified. Application of the rSFTSV-N protein based indirect IgG ELISA to the 115 serum samples showed results that perfectly matched those of the total antibody sandwich ELISA with a sensitivity and specificity of 100 %. The rSFTSV-N protein based indirect IgM ELISA missed 8 positive samples that were detected by the total antibody sandwich ELISA. The sensitivity and specificity of rSFTSV-N-IgM capture ELISA were 90.59 and 100 %, respectively. CONCLUSIONS: The rSFTSV-N protein is highly immunoreactive and a good target for use as an assay antigen in laboratory diagnosis. Its preparation is simpler in comparison with that used for the total antibody sandwich system. Our rSFTSV-N protein-based IgG and IgM ELISA systems have the advantage of distinguishing two types of antibodies and require small volume of serum sample only. They are safe to use for diagnosis of SFTS virus infection and especially fit in large-scale epidemiological investigations.",2015 Aug 4,"['Yu, Fuxun', 'Du, Yanhua', 'Huang, Xueyong', 'Ma, Hong', 'Xu, Bianli', 'Adungo, Ferdinard', 'Hayasaka, Daisuke', 'Buerano, Corazon C.', 'Morita, Kouichi']",Virol J,,,True
f831181b0266734c1f277c223956e61e0a42b350,PMC,Characterization of Ribosomal Frameshifting in Theiler's Murine Encephalomyelitis Virus,http://dx.doi.org/10.1128/JVI.01043-15,PMC4524249,26063423,CC BY,"Theiler's murine encephalomyelitis virus (TMEV) is a member of the genus Cardiovirus in the Picornaviridae, a family of positive-sense single-stranded RNA viruses. Previously, we demonstrated that in the related cardiovirus, Encephalomyocarditis virus, a programmed −1 ribosomal frameshift (−1 PRF) occurs at a conserved G_GUU_UUU sequence within the 2B-encoding region of the polyprotein open reading frame (ORF). Here we show that −1 PRF occurs at a similar site during translation of the TMEV genome. In addition, we demonstrate that a predicted 3′ RNA stem-loop structure at a noncanonical spacing downstream of the shift site is required for efficient frameshifting in TMEV and that frameshifting also requires virus infection. Mutating the G_GUU_UUU shift site to inhibit frameshifting results in an attenuated virus with reduced growth kinetics and a small-plaque phenotype. Frameshifting in the virus context was found to be extremely efficient at 74 to 82%, which, to our knowledge, is the highest frameshifting efficiency recorded to date for any virus. We propose that highly efficient −1 PRF in TMEV provides a mechanism to escape the confines of equimolar expression normally inherent in the single-polyprotein expression strategy of picornaviruses. IMPORTANCE Many viruses utilize programmed −1 ribosomal frameshifting (−1 PRF) to produce different protein products at a defined ratio, or to translate overlapping ORFs to increase coding capacity. With few exceptions, −1 PRF occurs on specific “slippery” heptanucleotide sequences and is stimulated by RNA structure beginning 5 to 9 nucleotides (nt) downstream of the slippery site. Here we describe an unusual case of −1 PRF in Theiler's murine encephalomyelitis virus (TMEV) that is extraordinarily efficient (74 to 82% of ribosomes shift into the alternative reading frame) and, in stark contrast to other examples of −1 PRF, is dependent upon a stem-loop structure beginning 14 nt downstream of the slippery site. Furthermore, in TMEV-based reporter constructs in transfected cells, efficient frameshifting is critically dependent upon virus infection. We suggest that TMEV evolved frameshifting as a novel mechanism for removing ribosomes from the message (a “ribosome sink”) to downregulate synthesis of the 3′-encoded replication proteins.",2015 Jun 10,"['Finch, Leanne K.', 'Ling, Roger', 'Napthine, Sawsan', 'Olspert, Allan', 'Michiels, Thomas', 'Lardinois, Cécile', 'Bell, Susanne', 'Loughran, Gary', 'Brierley, Ian', 'Firth, Andrew E.']",J Virol,,,False
975a7b5f0f9a7f9a03195cb5cd1a633ecd4e36f8,PMC,Characterization of Ribosomal Frameshifting in Theiler's Murine Encephalomyelitis Virus,http://dx.doi.org/10.1128/JVI.01043-15,PMC4524249,26063423,CC BY,"Theiler's murine encephalomyelitis virus (TMEV) is a member of the genus Cardiovirus in the Picornaviridae, a family of positive-sense single-stranded RNA viruses. Previously, we demonstrated that in the related cardiovirus, Encephalomyocarditis virus, a programmed −1 ribosomal frameshift (−1 PRF) occurs at a conserved G_GUU_UUU sequence within the 2B-encoding region of the polyprotein open reading frame (ORF). Here we show that −1 PRF occurs at a similar site during translation of the TMEV genome. In addition, we demonstrate that a predicted 3′ RNA stem-loop structure at a noncanonical spacing downstream of the shift site is required for efficient frameshifting in TMEV and that frameshifting also requires virus infection. Mutating the G_GUU_UUU shift site to inhibit frameshifting results in an attenuated virus with reduced growth kinetics and a small-plaque phenotype. Frameshifting in the virus context was found to be extremely efficient at 74 to 82%, which, to our knowledge, is the highest frameshifting efficiency recorded to date for any virus. We propose that highly efficient −1 PRF in TMEV provides a mechanism to escape the confines of equimolar expression normally inherent in the single-polyprotein expression strategy of picornaviruses. IMPORTANCE Many viruses utilize programmed −1 ribosomal frameshifting (−1 PRF) to produce different protein products at a defined ratio, or to translate overlapping ORFs to increase coding capacity. With few exceptions, −1 PRF occurs on specific “slippery” heptanucleotide sequences and is stimulated by RNA structure beginning 5 to 9 nucleotides (nt) downstream of the slippery site. Here we describe an unusual case of −1 PRF in Theiler's murine encephalomyelitis virus (TMEV) that is extraordinarily efficient (74 to 82% of ribosomes shift into the alternative reading frame) and, in stark contrast to other examples of −1 PRF, is dependent upon a stem-loop structure beginning 14 nt downstream of the slippery site. Furthermore, in TMEV-based reporter constructs in transfected cells, efficient frameshifting is critically dependent upon virus infection. We suggest that TMEV evolved frameshifting as a novel mechanism for removing ribosomes from the message (a “ribosome sink”) to downregulate synthesis of the 3′-encoded replication proteins.",2015 Jun 10,"['Finch, Leanne K.', 'Ling, Roger', 'Napthine, Sawsan', 'Olspert, Allan', 'Michiels, Thomas', 'Lardinois, Cécile', 'Bell, Susanne', 'Loughran, Gary', 'Brierley, Ian', 'Firth, Andrew E.']",J Virol,,,True
d38f4068c4bf5d99a9f4fc20b1914a3332a42ead,PMC,Phylogenetic analysis of avian infectious bronchitis virus S1 glycoprotein regions reveals emergence of a new genotype in Moroccan broiler chicken flocks,http://dx.doi.org/10.1186/s12985-015-0347-8,PMC4524495,26239707,CC BY,"BACKGROUND: Infectious bronchitis virus (IBV), a major pathogen of commercial poultry flocks, circulates in the form of several serotypes/genotypes. Only a few amino-acid changes in the S1 subunit of wild-type IBVS proteins may result in mutants unaffected by current vaccines. METHODS: Partial S1 gene sequences of 3 IBV isolates of the Moroccan Italy 02 genotype from vaccinated and unvaccinated broiler chicken flocks, located in southern and central regions of Morocco, were amplified by RT-PCR, sequenced, and aligned for phylogenetic and amino-acid similarity analyses. RESULTS: The three isolates were found genetically highly distant from known avian IBV based on partial sequences of their S1 genes: gammaCoV/chicken/Morocco/I01/2011(IBV/Morocco/01), gammaCoV/chicken/Morocco/I30/2010 (IBV/Morocco/30), and gammaCoV/chicken/Morocco/I38/2013 (IBV/Morocco/38), nucleotide sequence identities reached 89.5 % to 90.9 % among the three isolates. The deduced protein sequence identities ranged from 29.7 % (between IBV/Morocco/38 and Egypt SCU-14/2013-1) to 78.2 % (between IBV/Morocco/01 and Spain/05/866). Amino acid sequence comparison and phylogenetic analysis indicated the emergence of a new Moroccan genotype, clustering with regionally related isolates from Spain (Spain/05/866) and belonging to a new sub-genotype. CONCLUSION: Our sequencing results demonstrate a co-circulation of wild-type infectious bronchitis viruses in broiler chickens. These results justify permanent monitoring of circulating strains in order to rationally modify vaccination strategies to make them appropriate to the evolving field situation.",2015 Aug 4,"['Fellahi, Siham', 'EL Harrak, Mehdi', 'Ducatez, Mariette', 'Loutfi, Chafiqa', 'Koraichi, Saad Ibn Souda', 'Kuhn, Jens H.', 'Khayi, Slimane', 'EL Houadfi, Mohammed', 'Ennaji, My Mustapha']",Virol J,,,True
96f74d611693ebad68d8cd10862e9a972bd3bdc5,PMC,Evaluation of candidate vaccine approaches for MERS-CoV,http://dx.doi.org/10.1038/ncomms8712,PMC4525294,26218507,CC BY,"The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.",2015 Jul 28,"['Wang, Lingshu', 'Shi, Wei', 'Joyce, M. Gordon', 'Modjarrad, Kayvon', 'Zhang, Yi', 'Leung, Kwanyee', 'Lees, Christopher R.', 'Zhou, Tongqing', 'Yassine, Hadi M.', 'Kanekiyo, Masaru', 'Yang, Zhi-yong', 'Chen, Xuejun', 'Becker, Michelle M.', 'Freeman, Megan', 'Vogel, Leatrice', 'Johnson, Joshua C.', 'Olinger, Gene', 'Todd, John P.', 'Bagci, Ulas', 'Solomon, Jeffrey', 'Mollura, Daniel J.', 'Hensley, Lisa', 'Jahrling, Peter', 'Denison, Mark R.', 'Rao, Srinivas S.', 'Subbarao, Kanta', 'Kwong, Peter D.', 'Mascola, John R.', 'Kong, Wing-Pui', 'Graham, Barney S.']",Nat Commun,,,True
83a9e757fc42183eef4f36f50cf84044f7b780fb,PMC,Evaluation of candidate vaccine approaches for MERS-CoV,http://dx.doi.org/10.1038/ncomms8712,PMC4525294,26218507,CC BY,"The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.",2015 Jul 28,"['Wang, Lingshu', 'Shi, Wei', 'Joyce, M. Gordon', 'Modjarrad, Kayvon', 'Zhang, Yi', 'Leung, Kwanyee', 'Lees, Christopher R.', 'Zhou, Tongqing', 'Yassine, Hadi M.', 'Kanekiyo, Masaru', 'Yang, Zhi-yong', 'Chen, Xuejun', 'Becker, Michelle M.', 'Freeman, Megan', 'Vogel, Leatrice', 'Johnson, Joshua C.', 'Olinger, Gene', 'Todd, John P.', 'Bagci, Ulas', 'Solomon, Jeffrey', 'Mollura, Daniel J.', 'Hensley, Lisa', 'Jahrling, Peter', 'Denison, Mark R.', 'Rao, Srinivas S.', 'Subbarao, Kanta', 'Kwong, Peter D.', 'Mascola, John R.', 'Kong, Wing-Pui', 'Graham, Barney S.']",Nat Commun,,,True
bae5b0168a883973407af7229c5f3b59020cdfa4,PMC,Aeromonas salmonicida Infection Only Moderately Regulates Expression of Factors Contributing to Toll-Like Receptor Signaling but Massively Activates the Cellular and Humoral Branches of Innate Immunity in Rainbow Trout (Oncorhynchus mykiss),http://dx.doi.org/10.1155/2015/901015,PMC4525466,26266270,CC BY,"Toll-like receptors (TLRs) are known to detect a defined spectrum of microbial structures. However, the knowledge about the specificity of teleost Tlr factors for distinct pathogens is limited so far. We measured baseline expression profiles of 18 tlr genes and associated signaling factors in four immune-relevant tissues of rainbow trout Oncorhynchus mykiss. Intraperitoneal injection of a lethal dose of Aeromonas salmonicida subsp. salmonicida induced highly increased levels of cytokine mRNAs during a 72-hour postinfection (hpi) period. In contrast, only the fish-specific tlr22a2 and the downstream factor irak1 featured clearly increased transcript levels, while the mRNA concentrations of many other tlr genes decreased. Flow cytometry quantified cell trafficking after infection indicating a dramatic influx of myeloid cells into the peritoneum and a belated low level immigration of lymphoid cells. T and B lymphocytes were differentiated with RT-qPCR revealing that B lymphocytes emigrated from and T lymphocytes immigrated into head kidney. In conclusion, no specific TLR can be singled out as a dominant receptor for A. salmonicida. The recruitment of cellular factors of innate immunity rather than induced expression of pathogen receptors is hence of key importance for mounting a first immune defense against invading A. salmonicida.",2015 Jul 22,"['Brietzke, Andreas', 'Korytář, Tomáš', 'Jaros, Joanna', 'Köllner, Bernd', 'Goldammer, Tom', 'Seyfert, Hans-Martin', 'Rebl, Alexander']",J Immunol Res,,,True
506d16aa50b90556febfdfdcdfed1a017df40ce8,PMC,MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet,http://dx.doi.org/10.1186/s12933-015-0252-x,PMC4526192,26242235,CC BY,"BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. METHODS: MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. RESULTS: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. CONCLUSIONS: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0252-x) contains supplementary material, which is available to authorized users.",2015 Aug 5,"['He, Jun', 'Quintana, Megan T', 'Sullivan, Jenyth', 'L Parry, Traci', 'J Grevengoed, Trisha', 'Schisler, Jonathan C', 'Hill, Joseph A', 'Yates, Cecelia C', 'Mapanga, Rudo F', 'Essop, M Faadiel', 'Stansfield, William E', 'Bain, James R', 'Newgard, Christopher B', 'Muehlbauer, Michael J', 'Han, Yipin', 'Clarke, Brian A', 'Willis, Monte S']",Cardiovasc Diabetol,,,False
216552de85d6c86d4c92c8d66673332c6471bc2e,PMC,MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet,http://dx.doi.org/10.1186/s12933-015-0252-x,PMC4526192,26242235,CC BY,"BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. METHODS: MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. RESULTS: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. CONCLUSIONS: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0252-x) contains supplementary material, which is available to authorized users.",2015 Aug 5,"['He, Jun', 'Quintana, Megan T', 'Sullivan, Jenyth', 'L Parry, Traci', 'J Grevengoed, Trisha', 'Schisler, Jonathan C', 'Hill, Joseph A', 'Yates, Cecelia C', 'Mapanga, Rudo F', 'Essop, M Faadiel', 'Stansfield, William E', 'Bain, James R', 'Newgard, Christopher B', 'Muehlbauer, Michael J', 'Han, Yipin', 'Clarke, Brian A', 'Willis, Monte S']",Cardiovasc Diabetol,,,False
31ee178148fc34c988d2deb5637c98ef944c7a7a,PMC,MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet,http://dx.doi.org/10.1186/s12933-015-0252-x,PMC4526192,26242235,CC BY,"BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. METHODS: MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. RESULTS: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. CONCLUSIONS: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0252-x) contains supplementary material, which is available to authorized users.",2015 Aug 5,"['He, Jun', 'Quintana, Megan T', 'Sullivan, Jenyth', 'L Parry, Traci', 'J Grevengoed, Trisha', 'Schisler, Jonathan C', 'Hill, Joseph A', 'Yates, Cecelia C', 'Mapanga, Rudo F', 'Essop, M Faadiel', 'Stansfield, William E', 'Bain, James R', 'Newgard, Christopher B', 'Muehlbauer, Michael J', 'Han, Yipin', 'Clarke, Brian A', 'Willis, Monte S']",Cardiovasc Diabetol,,,False
fd33aae6b2e5c09fa0ea3afade3bc2cc836946cf,PMC,MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet,http://dx.doi.org/10.1186/s12933-015-0252-x,PMC4526192,26242235,CC BY,"BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. METHODS: MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. RESULTS: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. CONCLUSIONS: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0252-x) contains supplementary material, which is available to authorized users.",2015 Aug 5,"['He, Jun', 'Quintana, Megan T', 'Sullivan, Jenyth', 'L Parry, Traci', 'J Grevengoed, Trisha', 'Schisler, Jonathan C', 'Hill, Joseph A', 'Yates, Cecelia C', 'Mapanga, Rudo F', 'Essop, M Faadiel', 'Stansfield, William E', 'Bain, James R', 'Newgard, Christopher B', 'Muehlbauer, Michael J', 'Han, Yipin', 'Clarke, Brian A', 'Willis, Monte S']",Cardiovasc Diabetol,,,False
a00518a38dd5b19f2774ea3c2b530fd9595113e0,PMC,MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet,http://dx.doi.org/10.1186/s12933-015-0252-x,PMC4526192,26242235,CC BY,"BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. METHODS: MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. RESULTS: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. CONCLUSIONS: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0252-x) contains supplementary material, which is available to authorized users.",2015 Aug 5,"['He, Jun', 'Quintana, Megan T', 'Sullivan, Jenyth', 'L Parry, Traci', 'J Grevengoed, Trisha', 'Schisler, Jonathan C', 'Hill, Joseph A', 'Yates, Cecelia C', 'Mapanga, Rudo F', 'Essop, M Faadiel', 'Stansfield, William E', 'Bain, James R', 'Newgard, Christopher B', 'Muehlbauer, Michael J', 'Han, Yipin', 'Clarke, Brian A', 'Willis, Monte S']",Cardiovasc Diabetol,,,False
f29df5233e688dddd0286374e0993e43459fe04b,PMC,MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet,http://dx.doi.org/10.1186/s12933-015-0252-x,PMC4526192,26242235,CC BY,"BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer. However, specific mechanisms in the heart have not previously been described. Recent studies have implicated the muscle-specific ubiquitin ligase muscle ring finger-2 (MuRF2) in inhibiting the nuclear transcription factor SRF. Initial studies of MuRF2−/− hearts revealed enhanced PPAR activity, leading to the hypothesis that MuRF2 regulates PPAR activity by post-translational ubiquitination. METHODS: MuRF2−/− mice were challenged with a 26-week 60% fat diet designed to simulate obesity-mediated insulin resistance and diabetic cardiomyopathy. Mice were followed by conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1-regulated mRNA expression. RESULTS: MuRF2 protein levels increase ~20% during the development of diabetic cardiomyopathy induced by high fat diet. Compared to littermate wildtype hearts, MuRF2−/− hearts exhibit an exaggerated diabetic cardiomyopathy, characterized by an early onset systolic dysfunction, larger left ventricular mass, and higher heart weight. MuRF2−/− hearts had significantly increased PPARα- and PPARγ1-regulated gene expression by RT-qPCR, consistent with MuRF2’s regulation of these transcription factors in vivo. Mechanistically, MuRF2 mono-ubiquitinated PPARα and PPARγ1 in vitro, consistent with its non-degradatory role in diabetic cardiomyopathy. However, increasing MuRF2:PPARγ1 (>5:1) beyond physiological levels drove poly-ubiquitin-mediated degradation of PPARγ1 in vitro, indicating large MuRF2 increases may lead to PPAR degradation if found in other disease states. CONCLUSIONS: Mutations in MuRF2 have been described to contribute to the severity of familial hypertrophic cardiomyopathy. The present study suggests that the lack of MuRF2, as found in these patients, can result in an exaggerated diabetic cardiomyopathy. These studies also identify MuRF2 as the first ubiquitin ligase to regulate cardiac PPARα and PPARγ1 activities in vivo via post-translational modification without degradation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0252-x) contains supplementary material, which is available to authorized users.",2015 Aug 5,"['He, Jun', 'Quintana, Megan T', 'Sullivan, Jenyth', 'L Parry, Traci', 'J Grevengoed, Trisha', 'Schisler, Jonathan C', 'Hill, Joseph A', 'Yates, Cecelia C', 'Mapanga, Rudo F', 'Essop, M Faadiel', 'Stansfield, William E', 'Bain, James R', 'Newgard, Christopher B', 'Muehlbauer, Michael J', 'Han, Yipin', 'Clarke, Brian A', 'Willis, Monte S']",Cardiovasc Diabetol,,,True
74b1c6107f2da5209abaa2521b5a93d885e74cf5,PMC,Epidemic Wave Dynamics Attributable to Urban Community Structure: A Theoretical Characterization of Disease Transmission in a Large Network,http://dx.doi.org/10.2196/jmir.3720,PMC4526984,26156032,CC BY,"BACKGROUND: Multiple waves of transmission during infectious disease epidemics represent a major public health challenge, but the ecological and behavioral drivers of epidemic resurgence are poorly understood. In theory, community structure—aggregation into highly intraconnected and loosely interconnected social groups—within human populations may lead to punctuated outbreaks as diseases progress from one community to the next. However, this explanation has been largely overlooked in favor of temporal shifts in environmental conditions and human behavior and because of the difficulties associated with estimating large-scale contact patterns. OBJECTIVE: The aim was to characterize naturally arising patterns of human contact that are capable of producing simulated epidemics with multiple wave structures. METHODS: We used an extensive dataset of proximal physical contacts between users of a public Wi-Fi Internet system to evaluate the epidemiological implications of an empirical urban contact network. We characterized the modularity (community structure) of the network and then estimated epidemic dynamics under a percolation-based model of infectious disease spread on the network. We classified simulated epidemics as multiwave using a novel metric and we identified network structures that were critical to the network’s ability to produce multiwave epidemics. RESULTS: We identified robust community structure in a large, empirical urban contact network from which multiwave epidemics may emerge naturally. This pattern was fueled by a special kind of insularity in which locally popular individuals were not the ones forging contacts with more distant social groups. CONCLUSIONS: Our results suggest that ordinary contact patterns can produce multiwave epidemics at the scale of a single urban area without the temporal shifts that are usually assumed to be responsible. Understanding the role of community structure in epidemic dynamics allows officials to anticipate epidemic resurgence without having to forecast future changes in hosts, pathogens, or the environment.",2015 Jul 8,"['Hoen, Anne G', 'Hladish, Thomas J', 'Eggo, Rosalind M', 'Lenczner, Michael', 'Brownstein, John S', 'Meyers, Lauren Ancel']",J Med Internet Res,,,False
8bc561d5b5716c07c70a69f724f0cc96dcb2e40f,PMC,Epidemic Wave Dynamics Attributable to Urban Community Structure: A Theoretical Characterization of Disease Transmission in a Large Network,http://dx.doi.org/10.2196/jmir.3720,PMC4526984,26156032,CC BY,"BACKGROUND: Multiple waves of transmission during infectious disease epidemics represent a major public health challenge, but the ecological and behavioral drivers of epidemic resurgence are poorly understood. In theory, community structure—aggregation into highly intraconnected and loosely interconnected social groups—within human populations may lead to punctuated outbreaks as diseases progress from one community to the next. However, this explanation has been largely overlooked in favor of temporal shifts in environmental conditions and human behavior and because of the difficulties associated with estimating large-scale contact patterns. OBJECTIVE: The aim was to characterize naturally arising patterns of human contact that are capable of producing simulated epidemics with multiple wave structures. METHODS: We used an extensive dataset of proximal physical contacts between users of a public Wi-Fi Internet system to evaluate the epidemiological implications of an empirical urban contact network. We characterized the modularity (community structure) of the network and then estimated epidemic dynamics under a percolation-based model of infectious disease spread on the network. We classified simulated epidemics as multiwave using a novel metric and we identified network structures that were critical to the network’s ability to produce multiwave epidemics. RESULTS: We identified robust community structure in a large, empirical urban contact network from which multiwave epidemics may emerge naturally. This pattern was fueled by a special kind of insularity in which locally popular individuals were not the ones forging contacts with more distant social groups. CONCLUSIONS: Our results suggest that ordinary contact patterns can produce multiwave epidemics at the scale of a single urban area without the temporal shifts that are usually assumed to be responsible. Understanding the role of community structure in epidemic dynamics allows officials to anticipate epidemic resurgence without having to forecast future changes in hosts, pathogens, or the environment.",2015 Jul 8,"['Hoen, Anne G', 'Hladish, Thomas J', 'Eggo, Rosalind M', 'Lenczner, Michael', 'Brownstein, John S', 'Meyers, Lauren Ancel']",J Med Internet Res,,,False
38486671848611786384f2cc0a49066c5fca595f,PMC,Interdisciplinarity and Infectious Diseases: An Ebola Case Study,http://dx.doi.org/10.1371/journal.ppat.1004992,PMC4527690,26247831,CC BY,,2015 Aug 6,"['Ezenwa, Vanessa O.', 'Prieur-Richard, Anne-Helene', 'Roche, Benjamin', 'Bailly, Xavier', 'Becquart, Pierre', 'García-Peña, Gabriel E.', 'Hosseini, Parviez R.', 'Keesing, Felicia', 'Rizzoli, Annapaola', 'Suzán, Gerardo', 'Vignuzzi, Marco', 'Vittecoq, Marion', 'Mills, James N.', 'Guégan, Jean-François']",PLoS Pathog,,,True
078b6935fa30cd20a00da6c6182e85b41ab4d9c5,PMC,Damage/Danger Associated Molecular Patterns (DAMPs) Modulate Chlamydia pecorum and C. trachomatis Serovar E Inclusion Development In Vitro,http://dx.doi.org/10.1371/journal.pone.0134943,PMC4527707,26248286,CC0,"Persistence, more recently termed the chlamydial stress response, is a viable but non-infectious state constituting a divergence from the characteristic chlamydial biphasic developmental cycle. Damage/danger associated molecular patterns (DAMPs) are normal intracellular components or metabolites that, when released from cells, signal cellular damage/lysis. Purine metabolite DAMPs, including extracellular ATP and adenosine, inhibit chlamydial development in a species-specific manner. Viral co-infection has been shown to reversibly abrogate Chlamydia inclusion development, suggesting persistence/chlamydial stress. Because viral infection can cause host cell DAMP release, we hypothesized DAMPs may influence chlamydial development. Therefore, we examined the effect of extracellular ATP, adenosine, and cyclic AMP exposure, at 0 and 14 hours post infection, on C. pecorum and C. trachomatis serovar E development. In the absence of de novo host protein synthesis, exposure to DAMPs immediately post or at 14 hours post infection reduced inclusion size; however, the effect was less robust upon 14 hours post infection exposure. Additionally, upon exposure to DAMPs immediately post infection, bacteria per inclusion and subsequent infectivity were reduced in both Chlamydia species. These effects were reversible, and C. pecorum exhibited more pronounced recovery from DAMP exposure. Aberrant bodies, typical in virus-induced chlamydial persistence, were absent upon DAMP exposure. In the presence of de novo host protein synthesis, exposure to DAMPs immediately post infection reduced inclusion size, but only variably modulated chlamydial infectivity. Because chlamydial infection and other infections may increase local DAMP concentrations, DAMPs may influence Chlamydia infection in vivo, particularly in the context of poly-microbial infections.",2015 Aug 6,"['Leonard, Cory Ann', 'Schoborg, Robert V.', 'Borel, Nicole']",PLoS One,,,True
d31b2db65b2e8d40eee096d5e67185099c10c4d2,PMC,Basal Autophagy Is Required for Herpes simplex Virus-2 Infection,http://dx.doi.org/10.1038/srep12985,PMC4528227,26248741,CC BY,"Autophagy is a conserved catabolic process of the cell, which plays an important role in regulating plethora of infections. The role of autophagy in Herpes simplex virus-2 (HSV-2) infection is unknown. Here, we found that HSV-2 does not allow induction of an autophagic response to infection, but maintains basal autophagy levels mostly unchanged during productive infection. Thus, we investigated the importance of basal autophagy for HSV-2 infection, using pharmacological autophagy suppression or cells genetically deficient in an autophagy-essential gene (ATG5). Interference with basal autophagy flux in cells significantly reduced viral replication and diminished the infection. These results indicate that basal autophagy plays an indispensable role required for a productive infection. Importantly, this study draws a sharp distinction between induced and basal autophagy, where the former acts as a viral clearance mechanism abrogating infection, while the latter supports infection.",2015 Aug 7,"['Yakoub, Abraam M.', 'Shukla, Deepak']",Sci Rep,,,True
474dc8b54f9110f60b129220549c532355fe10b2,PMC,"The Dipeptidyl Peptidase Family, Prolyl Oligopeptidase, and Prolyl Carboxypeptidase in the Immune System and Inflammatory Disease, Including Atherosclerosis",http://dx.doi.org/10.3389/fimmu.2015.00387,PMC4528296,26300881,CC BY,"Research from over the past 20 years has implicated dipeptidyl peptidase (DPP) IV and its family members in many processes and different pathologies of the immune system. Most research has been focused on either DPPIV or just a few of its family members. It is, however, essential to consider the entire DPP family when discussing any one of its members. There is a substantial overlap between family members in their substrate specificity, inhibitors, and functions. In this review, we provide a comprehensive discussion on the role of prolyl-specific peptidases DPPIV, FAP, DPP8, DPP9, dipeptidyl peptidase II, prolyl carboxypeptidase, and prolyl oligopeptidase in the immune system and its diseases. We highlight possible therapeutic targets for the prevention and treatment of atherosclerosis, a condition that lies at the frontier between inflammation and cardiovascular disease.",2015 Aug 7,"['Waumans, Yannick', 'Baerts, Lesley', 'Kehoe, Kaat', 'Lambeir, Anne-Marie', 'De Meester, Ingrid']",Front Immunol,,,True
96a20376534b0725c4cbd316e15d003d2183436b,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,True
eb784c2597d60b7a250f358bce5192afbc5ee52c,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
51f014265335a090e751bab6d11681af1c9eda3a,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
9f1d8594e18a9810c76e8df9d0e45eb96107988f,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
a3b4eba0e843b0214bd7c43535c87dfb7406e16a,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
fa58494e76abe64e7e107171ace85c5cd6ed6980,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
9ca2858fbcf3604a833c3334703f62b92e524b6c,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
fd5e2e2f8024eecb3611e4ca20d53aca0b0a9f32,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
1621c4ee9abc3983f8d2b8bd83270cc10ee04189,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
4af692eecd2b11d44d07ebd686017780c90d06bf,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
0e9a9468b6f5cca7ff28d5df02da29b65b7ac07b,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
1df9d3600307acda32a25a59dfe68d06222ba6f3,PMC,A Novel Virus Causes Scale Drop Disease in Lates calcarifer,http://dx.doi.org/10.1371/journal.ppat.1005074,PMC4529248,26252390,CC BY,"From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch’s postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.",2015 Aug 7,"['de Groof, Ad', 'Guelen, Lars', 'Deijs, Martin', 'van der Wal, Yorick', 'Miyata, Masato', 'Ng, Kah Sing', 'van Grinsven, Lotte', 'Simmelink, Bartjan', 'Biermann, Yvonne', 'Grisez, Luc', 'van Lent, Jan', 'de Ronde, Anthony', 'Chang, Siow Foong', 'Schrier, Carla', 'van der Hoek, Lia']",PLoS Pathog,,,False
51f88d6a65a66742a19ec634400f8315fda5811e,PMC,Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach,http://dx.doi.org/10.1186/s40203-015-0011-4,PMC4529428,26820892,CC BY,"PURPOSE: Ebola virus (EBOV) is such kind of virus which is responsible for 23,825 cases and 9675 deaths worldwide only in 2014 and with an average diseases fatality rate between 25 % and 90 %. Although, medical technology has tried to handle the problems, there is no Food and Drug Administration (FDA)-approved therapeutics or vaccines available for the prevention, post exposure, or treatment of Ebola virus disease (EVD). METHODS: In the present study, we used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of EBOV. BioEdit v7.2.3 sequence alignment editor, Jalview v2 and CLC Sequence Viewer v7.0.2 were used for the initial sequence analysis for securing the conservancy from the sequences. Later the Immune Epitope Database and Analysis Resource (IEDB-AR) was used for the identification of T-cell and B-cellepitopes associated with type I and II major histocompatibility complex molecules analysis. Finally, the population coverage analysis was employed. RESULTS: The core epitope “FRYEFTAPF” was found to be the most potential one, with 100 % conservancy among all the strains of EBOV. It also interacted with both type I and II major histocompatibility complex molecules and is considered as nonallergenic in nature. Finally, with impressive cumulative population coverage of 99.87 % for the both MHC-I and MHC-II class throughout the world population was found for the proposed epitope. CONCLUSION: To end, the projected peptide gave us a solid stand to propose for vaccine consideration and that might be experimented for its potency in eliciting immunity through humoral and cell mediated immune responses in vitro and in vivo. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40203-015-0011-4) contains supplementary material, which is available to authorized users.",2015 Aug 8,"['Oany, Arafat Rahman', 'Sharmin, Tahmina', 'Chowdhury, Afrin Sultana', 'Jyoti, Tahmina Pervin', 'Hasan, Md. Anayet']",In Silico Pharmacol,,,True
15f149f2f2ca015d5b8b5c6ef59595c907f4c01f,PMC,Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization,http://dx.doi.org/10.1186/s40064-015-1207-0,PMC4529844,26266076,CC BY,"Pseudomonasaeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter- and intra-individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly more prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-1207-0) contains supplementary material, which is available to authorized users.",2015 Aug 9,"['Keravec, Marlène', 'Mounier, Jérôme', 'Prestat, Emmanuel', 'Vallet, Sophie', 'Jansson, Janet K', 'Burgaud, Gaëtan', 'Rosec, Sylvain', 'Gouriou, Stéphanie', 'Rault, Gilles', 'Coton, Emmanuel', 'Barbier, Georges', 'Héry-Arnaud, Geneviève']",Springerplus,,,False
1a3bac899966e4d132f98e04fbe6132170568e00,PMC,Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization,http://dx.doi.org/10.1186/s40064-015-1207-0,PMC4529844,26266076,CC BY,"Pseudomonasaeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter- and intra-individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly more prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-1207-0) contains supplementary material, which is available to authorized users.",2015 Aug 9,"['Keravec, Marlène', 'Mounier, Jérôme', 'Prestat, Emmanuel', 'Vallet, Sophie', 'Jansson, Janet K', 'Burgaud, Gaëtan', 'Rosec, Sylvain', 'Gouriou, Stéphanie', 'Rault, Gilles', 'Coton, Emmanuel', 'Barbier, Georges', 'Héry-Arnaud, Geneviève']",Springerplus,,,False
d338fd85fb47b5cb4d62c6ec0b753f4596d5b515,PMC,Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization,http://dx.doi.org/10.1186/s40064-015-1207-0,PMC4529844,26266076,CC BY,"Pseudomonasaeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter- and intra-individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly more prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-1207-0) contains supplementary material, which is available to authorized users.",2015 Aug 9,"['Keravec, Marlène', 'Mounier, Jérôme', 'Prestat, Emmanuel', 'Vallet, Sophie', 'Jansson, Janet K', 'Burgaud, Gaëtan', 'Rosec, Sylvain', 'Gouriou, Stéphanie', 'Rault, Gilles', 'Coton, Emmanuel', 'Barbier, Georges', 'Héry-Arnaud, Geneviève']",Springerplus,,,False
6d3e2a9b44f902aba943050ec1dbd4cd0b85309c,PMC,Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization,http://dx.doi.org/10.1186/s40064-015-1207-0,PMC4529844,26266076,CC BY,"Pseudomonasaeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter- and intra-individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly more prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-015-1207-0) contains supplementary material, which is available to authorized users.",2015 Aug 9,"['Keravec, Marlène', 'Mounier, Jérôme', 'Prestat, Emmanuel', 'Vallet, Sophie', 'Jansson, Janet K', 'Burgaud, Gaëtan', 'Rosec, Sylvain', 'Gouriou, Stéphanie', 'Rault, Gilles', 'Coton, Emmanuel', 'Barbier, Georges', 'Héry-Arnaud, Geneviève']",Springerplus,,,True
c1590dca1224c338b4163beacf9a838e7caec9c8,PMC,Affect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections,http://dx.doi.org/10.3389/fmed.2015.00055,PMC4530667,26322310,CC BY,"Children born preterm often exhibit reduced lung function and increased severity of response to respiratory viruses, suggesting that premature birth has compromised proper development of the respiratory epithelium and innate immune defenses. Increasing evidence suggests that premature birth promotes aberrant lung development likely due to the neonatal oxygen transition occurring before pulmonary development has matured. Given that preterm infants are born at a point of time where their immune system is also still developing, early life oxygen exposure may also be disrupting proper development of innate immunity. Here, we review current literature in hopes of stimulating research that enhances understanding of how the oxygen environment at birth influences lung development and host defense. This knowledge may help identify those children at risk for disease and ideally culminate in the development of novel therapies that improve their health.",2015 Aug 10,"['Domm, William', 'Misra, Ravi S.', 'O’Reilly, Michael A.']",Front Med (Lausanne),,,True
cb820c7373e5c272cc31065db8579e927176be72,PMC,Striding Toward Malaria Elimination in China,http://dx.doi.org/10.4269/ajtmh.15-0391,PMC4530732,26078325,CC BY,,2015 Aug 5,"['Hsiang, Michelle S.', 'Gosling, Roly D.']",Am J Trop Med Hyg,,,True
9c2c85e5e00aed9437ada6a93643d1aa660b59c4,PMC,"Malaria in Zhejiang Province, China, from 2005 to 2014",http://dx.doi.org/10.4269/ajtmh.15-0080,PMC4530752,26078321,CC BY,"To summarize the changing epidemiological characteristics of malaria in Zhejiang Province, China, we collected data on malaria from the Chinese Notifiable Disease Reporting System (NDRS) and analyzed them. A total of 2,738 malaria cases were identified in Zhejiang Province from 2005 to 2014, of which 2,018 were male and 720 were female. Notably, only 7% of malaria cases were indigenous and the other cases were all imported. The number of malaria cases increased from 2005 to 2007, peaked in 2007, and then decreased from 2007 to 2011. There were no indigenous cases from 2012 to 2014. Of all cases, 68% of cases contracted Plasmodium vivax, 27% of cases contracted P. falciparum, and two cases contracted P. malariae. About 88% of malaria cases during 2005–2011 occurred yearly between May and October, but the number of malaria cases in different months during 2012–2014 was similar. The median age was 33 years, and 1,892 cases occurred in persons aged 20–50 years. The proportion of businessmen increased and the proportion of migrant laborers decreased in recent years. The median time from illness onset to confirmation of malaria cases was 5 days and it decreased from 2005 to 2014. Some epidemiological characteristics of malaria have changed, and businessmen are the emphases to surveillance in every month.",2015 Aug 5,"['Chen, Hualiang', 'Yao, Linong', 'Zhang, Lingling', 'Zhang, Xuan', 'Lu, Qiaoyi', 'Yu, Kegen', 'Ruan, Wei']",Am J Trop Med Hyg,,,True
5229d13f7a121dfc9a455d2ec0807e3966da3e19,PMC,NMR and MD Studies Reveal That the Isolated Dengue NS3 Protease Is an Intrinsically Disordered Chymotrypsin Fold Which Absolutely Requests NS2B for Correct Folding and Functional Dynamics,http://dx.doi.org/10.1371/journal.pone.0134823,PMC4530887,26258523,CC BY,"Dengue genome encodes a two component protease complex (NS2B-NS3pro) essential for the viral maturation/infectivity, thus representing a key drug target. Previously, due to its “complete insolubility”, the isolated NS3pro could not be experimentally studied and it remains elusive what structure it adopts without NS2B and why NS2B is indispensable. Here as facilitated by our previous discovery, the isolated NS3pro has been surprisingly deciphered by NMR to be the first intrinsically-disordered chymotrypsin-like fold, which exists in a loosely-packed state with non-native long-range interactions as revealed by paramagnetic relaxation enhancement (PRE). The disordered NS3pro appears to be needed for binding a human host factor to trigger the membrane remodeling. Moreover, we have in vitro refolded the NS3pro in complex with either NS2B (48–100) or the full-length NS2B (1–130) anchored into the LMPC micelle, and the two complexes have similar activities but different dynamics. We also performed molecular dynamics (MD) simulations and the results revealed that NS2B shows the highest structural fluctuations in the complex, thus providing the dynamic basis for the observation on its conformational exchange between open and closed states. Remarkably, the NS2B cofactor plays a central role in maintaining the correlated motion network required for the catalysis as we previously decoded for the SARS 3CL protease. Indeed, a truncated NS2B (48–100;Δ77–84) with the flexible loop deleted is able to trap the NS2B-NS3pro complex in a highly dynamic and catalytically-impotent state. Taken together, our study implies potential strategies to perturb the NS2B-NS3pro interface for design of inhibitors for treating dengue infection.",2015 Aug 10,"['Gupta, Garvita', 'Lim, Liangzhong', 'Song, Jianxing']",PLoS One,,,True
914636db7f8a6361126e805e4abd3c8a8d5ab31f,PMC,Challenges and Strategies of Laboratory Diagnosis for Newly Emerging Influenza Viruses in Taiwan: A Decade after SARS,http://dx.doi.org/10.1155/2015/805306,PMC4531154,26290876,CC BY,"Since the first case of severe acute respiratory syndrome (SARS) in Taiwan was identified in March 2003, viral respiratory infections, in particular the influenza virus, have become a national public health concern. Taiwan would face a serious threat of public health problems if another SARS epidemic overlapped with a flu outbreak. After SARS, the Taiwan Centers for Disease Control accelerated and strengthened domestic research on influenza and expanded the exchange of information with international counterparts. The capacity of influenza A to cross species barriers presents a potential threat to human health. Given the mutations of avian flu viruses such as H7N9, H6N1, and H10N8, all countries, including Taiwan, must equip themselves to face a possible epidemic or pandemic. Such preparedness requires global collaboration.",2015 Jul 28,"['Lin, Jih-Hui', 'Wu, Ho-Sheng']",Biomed Res Int,,,True
6d4c934e5babea34af1b80d784ce9422735c9dc4,PMC,Real-time digital pathogen surveillance — the time is now,http://dx.doi.org/10.1186/s13059-015-0726-x,PMC4531805,27391693,CC BY,"It is time to shake up public health surveillance. New technologies for sequencing, aided by friction-free approaches to data sharing, could have an impact on public health efforts.",2015 Jul 30,"['Gardy, Jennifer', 'Loman, Nicholas J.', 'Rambaut, Andrew']",Genome Biol,,,True
795bd84388973214e4b97ea23b80a9dc4e481117,PMC,E3 Ubiquitin Ligase NEDD4 Promotes Influenza Virus Infection by Decreasing Levels of the Antiviral Protein IFITM3,http://dx.doi.org/10.1371/journal.ppat.1005095,PMC4532365,26263374,CC BY,"Interferon (IFN)-induced transmembrane protein 3 (IFITM3) is a cell-intrinsic factor that limits influenza virus infections. We previously showed that IFITM3 degradation is increased by its ubiquitination, though the ubiquitin ligase responsible for this modification remained elusive. Here, we demonstrate that the E3 ubiquitin ligase NEDD4 ubiquitinates IFITM3 in cells and in vitro. This IFITM3 ubiquitination is dependent upon the presence of a PPxY motif within IFITM3 and the WW domain-containing region of NEDD4. In NEDD4 knockout mouse embryonic fibroblasts, we observed defective IFITM3 ubiquitination and accumulation of high levels of basal IFITM3 as compared to wild type cells. Heightened IFITM3 levels significantly protected NEDD4 knockout cells from infection by influenza A and B viruses. Similarly, knockdown of NEDD4 in human lung cells resulted in an increase in steady state IFITM3 and a decrease in influenza virus infection, demonstrating a conservation of this NEDD4-dependent IFITM3 regulatory mechanism in mouse and human cells. Consistent with the known association of NEDD4 with lysosomes, we demonstrate for the first time that steady state turnover of IFITM3 occurs through the lysosomal degradation pathway. Overall, this work identifies the enzyme NEDD4 as a new therapeutic target for the prevention of influenza virus infections, and introduces a new paradigm for up-regulating cellular levels of IFITM3 independently of IFN or infection.",2015 Aug 11,"['Chesarino, Nicholas M.', 'McMichael, Temet M.', 'Yount, Jacob S.']",PLoS Pathog,,,True
4518da3d4fdddd13a397a1fd68ce915512615db2,PMC,Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan,http://dx.doi.org/10.1371/journal.pone.0133910,PMC4532476,26263554,CC BY,"BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.",2015 Aug 11,"['Li, Yao-Tsun', 'Ko, Hui-Ying', 'Lee, Chang-Chun David', 'Lai, Ching-Yu', 'Kao, Chuan-Liang', 'Yang, Chinglai', 'Wang, Won-Bo', 'King, Chwan-Chuen']",PLoS One,,,True
5138729644d04e24590ea0124ff60cdd896c0bad,PMC,Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan,http://dx.doi.org/10.1371/journal.pone.0133910,PMC4532476,26263554,CC BY,"BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.",2015 Aug 11,"['Li, Yao-Tsun', 'Ko, Hui-Ying', 'Lee, Chang-Chun David', 'Lai, Ching-Yu', 'Kao, Chuan-Liang', 'Yang, Chinglai', 'Wang, Won-Bo', 'King, Chwan-Chuen']",PLoS One,,,False
695b24880d22f32b2f5648316d56d9e7bb26e0cb,PMC,Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan,http://dx.doi.org/10.1371/journal.pone.0133910,PMC4532476,26263554,CC BY,"BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.",2015 Aug 11,"['Li, Yao-Tsun', 'Ko, Hui-Ying', 'Lee, Chang-Chun David', 'Lai, Ching-Yu', 'Kao, Chuan-Liang', 'Yang, Chinglai', 'Wang, Won-Bo', 'King, Chwan-Chuen']",PLoS One,,,False
1142b43a1c754a62675eeb7ae78cf4fa78bc60fa,PMC,Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan,http://dx.doi.org/10.1371/journal.pone.0133910,PMC4532476,26263554,CC BY,"BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.",2015 Aug 11,"['Li, Yao-Tsun', 'Ko, Hui-Ying', 'Lee, Chang-Chun David', 'Lai, Ching-Yu', 'Kao, Chuan-Liang', 'Yang, Chinglai', 'Wang, Won-Bo', 'King, Chwan-Chuen']",PLoS One,,,False
f9e825f3e3cb781127402da99ebbc6e2a5ccbda1,PMC,Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan,http://dx.doi.org/10.1371/journal.pone.0133910,PMC4532476,26263554,CC BY,"BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.",2015 Aug 11,"['Li, Yao-Tsun', 'Ko, Hui-Ying', 'Lee, Chang-Chun David', 'Lai, Ching-Yu', 'Kao, Chuan-Liang', 'Yang, Chinglai', 'Wang, Won-Bo', 'King, Chwan-Chuen']",PLoS One,,,False
b963e160bbcb75fc97ff2b69d0762d27343cb568,PMC,Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan,http://dx.doi.org/10.1371/journal.pone.0133910,PMC4532476,26263554,CC BY,"BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.",2015 Aug 11,"['Li, Yao-Tsun', 'Ko, Hui-Ying', 'Lee, Chang-Chun David', 'Lai, Ching-Yu', 'Kao, Chuan-Liang', 'Yang, Chinglai', 'Wang, Won-Bo', 'King, Chwan-Chuen']",PLoS One,,,False
8b4973c7d257f7db1109925842617522a9256b3e,PMC,Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan,http://dx.doi.org/10.1371/journal.pone.0133910,PMC4532476,26263554,CC BY,"BACKGROUND: Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. METHODS: Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. RESULTS: The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. CONCLUSION: These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.",2015 Aug 11,"['Li, Yao-Tsun', 'Ko, Hui-Ying', 'Lee, Chang-Chun David', 'Lai, Ching-Yu', 'Kao, Chuan-Liang', 'Yang, Chinglai', 'Wang, Won-Bo', 'King, Chwan-Chuen']",PLoS One,,,False
3e8286a0531a46c267f34d20e60a4754c2391a09,PMC,Central Hypoventilation: A Case Study of Issues Associated with Travel Medicine and Respiratory Infection,http://dx.doi.org/10.1155/2015/647139,PMC4532870,26294997,CC BY,"Aim. We presented the case of a child with central hypoventilation syndrome (CHS) to highlight issues that need to be considered in planning long-haul flight and problems that may arise during the flight. Case. The pediatric intensive care unit (PICU) received a child with central hypoventilation syndrome (Ondine's curse) on nocturnal ventilatory support who travelled to Hong Kong on a make-a-wish journey. He was diagnosed with central hypoventilation and had been well managed in Canada. During a long-haul aviation travel, he developed respiratory symptoms and desaturations. The child arrived in Hong Kong and his respiratory symptoms persisted. He was taken to a PICU for management. The child remained well and investigations revealed no pathogen to account for his respiratory infection. He went on with his make-a-wish journey. Conclusions. Various issues of travel medicine such as equipment, airline arrangement, in-flight ventilatory support, travel insurance, and respiratory infection are explored and discussed. This case illustrates that long-haul air travel is possible for children with respiratory compromise if anticipatory preparation is timely arranged.",2015 Jul 29,"['Hon, Kam Lun', 'Leung, Alexander K. C.', 'Li, Albert M. C.', 'Ng, Daniel K. K.']",Case Rep Pediatr,,,True
e88ddb14ceee73a1db00d2991c683b872e747b33,PMC,Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease,http://dx.doi.org/10.1371/journal.pone.0135640,PMC4534143,26267139,CC BY,"To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (2009–2010, 2011–2012, and 2013–2014). Human bocavirus was detected using the respiratory virus panel fast assay and real-time PCR. Of the 1,823 nasopharyngeal samples, 104 (5.7%) were positive for hBoV; a similar prevalence was observed in all three periods studied. Among hBoV-infected children, 53.8% were between 1–2 years old, and hBoV was detected alone in 57/104 (54.8%) cases. All of the detected hBoV strains belonged to genotype 1. The median hBoV load was significantly higher in samples containing strains with both the N546H and T590S mutations compared to other samples (p<0.05). Children with a single hBoV-1 infection more frequently had upper respiratory tract infections (URTIs) than those who were co-infected (37.0% vs 17.8%, respectively, p = 0.04). The duration of hospitalization was longer among children with high viral loads than that observed among children with low viral loads (8.0 ±2.2 days vs 5.0 ±1.5 days, respectively, p = 0.03), and the use of aerosol therapy was more frequent among children with high viral loads than among those with low viral loads (77.1% vs 55.7%, respectively, p = 0.04). This study shows that hBoV is a relatively uncommon but stable infectious agent in children and that hBoV1 seems to be the only strain detected in Italy in respiratory samples. From a clinical point of view, hBoV1 seems to have in the majority of healthy children relatively low clinical relevance. Moreover, the viral load influences only the duration of hospitalization and the use of aerosol therapy without any association with the site of the respiratory disease.",2015 Aug 12,"['Principi, Nicola', 'Piralla, Antonio', 'Zampiero, Alberto', 'Bianchini, Sonia', 'Umbrello, Giulia', 'Scala, Alessia', 'Bosis, Samantha', 'Fossali, Emilio', 'Baldanti, Fausto', 'Esposito, Susanna']",PLoS One,,,True
56e7f3e210952c559633020f5910284c76111fde,PMC,Detection and molecular characterisation of bovine corona and toroviruses from Croatian cattle,http://dx.doi.org/10.1186/s12917-015-0511-9,PMC4535285,26268320,CC BY,"BACKGROUND: Bovine coronavirus (BCoV) together with bovine torovirus (BToV), both members of the Coronaviridae family, order Nidovirales are the most common viral enteric pathogens. Although studied separately, their joint occurrence and the molecular diversity in cattle in Croatia have not been investigated. METHODS: A survey is carried out on 101 fecal samples from diarrheic young and adult cattle during the 3-year period from i) one large dairy herd, ii) four small herds and iii) three nasal and paired fecal samples from calves with symptoms of respiratory disease. Samples were submitted to RT-PCR and sequencing for BCoV Nucleocapsid gene, BCoV Spike gene and BToV Spike gene. RESULTS: BCoV was detected in 78.8 % of fecal samples from symptomatic cattle and three nasal and paired fecal samples from calves with respiratory symptoms. BToV was detected in 43.2 % of fecal samples from symptomatic cattle and a fecal sample from calves with respiratory symptoms. Molecular characterisation of those viruses revealed some nucleotide and aminoacid differences in relation to reference strains. CONCLUSIONS: BToV should be regarded as a relevant pathogen for cattle that plays a synergistic role in mixed enteric infections.",2015 Aug 13,"['Lojkić, Ivana', 'Krešić, Nina', 'Šimić, Ivana', 'Bedeković, Tomislav']",BMC Vet Res,,,True
06094b031f02c0307da315a1428394c2c075ff2a,PMC,"Complete Genome Sequence of Middle East Respiratory Syndrome Coronavirus KOR/KNIH/002_05_2015, Isolated in South Korea",http://dx.doi.org/10.1128/genomeA.00787-15,PMC4536669,26272558,CC BY,"The full genome sequence of a Middle East respiratory syndrome coronavirus (MERS-CoV) was identified from cultured and isolated in Vero cells. The viral genome sequence has high similarity to 53 human MERS-CoVs, ranging from 99.5% to 99.8% at the nucleotide level.",2015 Aug 13,"['Kim, You-Jin', 'Cho, Yong-Joon', 'Kim, Dae-Won', 'Yang, Jeong-Sun', 'Kim, Hak', 'Park, SungHan', 'Han, Young Woo', 'Yun, Mi-ran', 'Lee, Han Saem', 'Kim, A-Reum', 'Heo, Deok Rim', 'Kim, Joo Ae', 'Kim, Su Jin', 'Jung, Hee-Dong', 'Kim, Namil', 'Yoon, Seok-Hwan', 'Nam, Jeong-Gu', 'Kang, Hae Ji', 'Cheong, Hyang-Min', 'Lee, Joo-Shil', 'Chun, Jongsik', 'Kim, Sung Soon']",Genome Announc,,,True
60721983c03cfb1fd6e277fb6cc20bd117a3df80,PMC,Complete Genome Sequence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) from the First Imported MERS-CoV Case in China,http://dx.doi.org/10.1128/genomeA.00818-15,PMC4536671,26272560,CC BY,"On 26 May 2015, an imported Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in Guangdong Province, China, and found to be closely related to the MERS-CoV strain prevalent in South Korea. The full genome of the ChinaGD01 strain was sequenced and analyzed to investigate the epidemiology and evolution of MERS-CoV circulating in South Korea and China.",2015 Aug 13,"['Lu, Roujian', 'Wang, Yanqun', 'Wang, Wenling', 'Nie, Kai', 'Zhao, Yanjie', 'Su, Juan', 'Deng, Yao', 'Zhou, Weimin', 'Li, Yang', 'Wang, Huijuan', 'Wang, Wen', 'Ke, Changwen', 'Ma, Xuejun', 'Wu, Guizhen', 'Tan, Wenjie']",Genome Announc,,,True
c9cd7adce6639f51a4ee3e4bc7904eff851de25f,PMC,Complete Genome Sequence of the Porcine Epidemic Diarrhea Virus Variant Tottori2/JPN/2014,http://dx.doi.org/10.1128/genomeA.00877-15,PMC4536677,26272566,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a cause of diarrhea outbreaks at swine farms, causing vomiting, severe diarrhea, and mortality in piglets. We sequenced and analyzed the complete genome of recently isolated strains. Tottori2/JPN/2014, one of the sequenced PEDV strains, had a unique large deletion in the S gene.",2015 Aug 13,"['Murakami, Satoshi', 'Miyazaki, Ayako', 'Takahashi, Osamu', 'Hashizume, Wataru', 'Hase, Yoichi', 'Ohashi, Seiichi', 'Suzuki, Tohru']",Genome Announc,,,True
cb763a61411514366d16bb2571461b6df1361517,PMC,Tropism and Induction of Cytokines in Human Embryonic-Stem Cells-Derived Neural Progenitors upon Inoculation with Highly- Pathogenic Avian H5N1 Influenza Virus,http://dx.doi.org/10.1371/journal.pone.0135850,PMC4537284,26274828,CC BY,"Central nervous system (CNS) dysfunction caused by neurovirulent influenza viruses is a dreaded complication of infection, and may play a role in some neurodegenerative conditions, such as Parkinson-like diseases and encephalitis lethargica. Although CNS infection by highly pathogenic H5N1 virus has been demonstrated, it is unknown whether H5N1 infects neural progenitor cells, nor whether such infection plays a role in the neuroinflammation and neurodegeneration. To pursue this question, we infected human neural progenitor cells (hNPCs) differentiated from human embryonic stem cells in vitro with H5N1 virus, and studied the resulting cytopathology, cytokine expression, and genes involved in the differentiation. Human embryonic stem cells (BG01) were maintained and differentiated into the neural progenitors, and then infected by H5N1 virus (A/Chicken/Thailand/CUK2/04) at a multiplicity of infection of 1. At 6, 24, 48, and 72 hours post-infection (hpi), cytopathic effects were observed. Then cells were characterized by immunofluorescence and electron microscopy, supernatants quantified for virus titers, and sampled cells studied for candidate genes.The hNPCs were susceptible to H5N1 virus infection as determined by morphological observation and immunofluorescence. The infection was characterized by a significant up-regulation of TNF-α gene expression, while expressions of IFN-α2, IFN-β1, IFN-γ and IL-6 remained unchanged compared to mock-infected controls. Moreover, H5N1 infection did not appear to alter expression of neuronal and astrocytic markers of hNPCs, such as β-III tubulin and GFAP, respectively. The results indicate that hNPCs support H5N1 virus infection and may play a role in the neuroinflammation during acute viral encephalitis.",2015 Aug 14,"['Pringproa, Kidsadagon', 'Rungsiwiwut, Ruttachuk', 'Tantilertcharoen, Rachod', 'Praphet, Reunkeaw', 'Pruksananonda, Kamthorn', 'Baumgärtner, Wolfgang', 'Thanawongnuwech, Roongroje']",PLoS One,,,True
023af2216525c16fa52a75b99cc91ebb03e93107,PMC,Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27,http://dx.doi.org/10.1038/srep13133,PMC4539535,26281793,CC BY,"The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans with an approximately 30% mortality rate. The envelope spike glycoprotein on the surface of MERS-CoV mediates receptor binding, membrane fusion, and viral entry. We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. Here we determined the crystal structure of MERS-CoV RBD bound to the Fab fragment of MERS-27 antibody at 3.20 Å resolution. The MERS-27 epitope in the RBD overlaps with the binding site of the MERS-CoV receptor DPP4. Further biochemical, viral entry, and neutralization analyses identified two critical residues in the RBD for both MERS-27 recognition and DPP4 binding. One of the residues, Trp535, was found to function as an anchor residue at the binding interface with MERS-27. Upon receptor binding, Trp535 interacts with the N-linked carbohydrate moiety of DPP4. Thus, MERS-27 inhibits MERS-CoV infection by directly blocking both protein-protein and protein-carbohydrate interactions between MERS-CoV RBD and DPP4. These results shed light on the molecular basis of MERS-27 neutralization and will assist in the optimization of MERS-27 as a tool to combat MERS-CoV infection.",2015 Aug 18,"['Yu, Xiaojuan', 'Zhang, Senyan', 'Jiang, Liwei', 'Cui, Ye', 'Li, Dongxia', 'Wang, Dongli', 'Wang, Nianshuang', 'Fu, Lili', 'Shi, Xuanlin', 'Li, Ziqiang', 'Zhang, Linqi', 'Wang, Xinquan']",Sci Rep,,,True
b8f48280d1c187776d6fc38cea706f8b5a269faf,PMC,Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27,http://dx.doi.org/10.1038/srep13133,PMC4539535,26281793,CC BY,"The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans with an approximately 30% mortality rate. The envelope spike glycoprotein on the surface of MERS-CoV mediates receptor binding, membrane fusion, and viral entry. We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. Here we determined the crystal structure of MERS-CoV RBD bound to the Fab fragment of MERS-27 antibody at 3.20 Å resolution. The MERS-27 epitope in the RBD overlaps with the binding site of the MERS-CoV receptor DPP4. Further biochemical, viral entry, and neutralization analyses identified two critical residues in the RBD for both MERS-27 recognition and DPP4 binding. One of the residues, Trp535, was found to function as an anchor residue at the binding interface with MERS-27. Upon receptor binding, Trp535 interacts with the N-linked carbohydrate moiety of DPP4. Thus, MERS-27 inhibits MERS-CoV infection by directly blocking both protein-protein and protein-carbohydrate interactions between MERS-CoV RBD and DPP4. These results shed light on the molecular basis of MERS-27 neutralization and will assist in the optimization of MERS-27 as a tool to combat MERS-CoV infection.",2015 Aug 18,"['Yu, Xiaojuan', 'Zhang, Senyan', 'Jiang, Liwei', 'Cui, Ye', 'Li, Dongxia', 'Wang, Dongli', 'Wang, Nianshuang', 'Fu, Lili', 'Shi, Xuanlin', 'Li, Ziqiang', 'Zhang, Linqi', 'Wang, Xinquan']",Sci Rep,,,False
2fe87abe58e092dfdabc0599ce8b31df6e49d4db,PMC,Results of an online questionnaire to survey calf management practices on dairy cattle breeding farms in Austria and to estimate differences in disease incidences depending on farm structure and management practices,http://dx.doi.org/10.1186/s13028-015-0134-y,PMC4539725,26282551,CC BY,"BACKGROUND: Calf disease may result in great economic losses. To implement prevention strategies it is important to gain information on management and to point out risk factors. The objective of this internet based survey was to describe calf management practices on registered dairy breeding farms in Austria and to estimate differences in calf disease incidences depending on farm structure and management practices. RESULTS: A total of 1287 questionnaires were finally analysed (response rate 12.2 %). Herd characteristics and regional distribution of farms indicated that this survey gives a good overview on calf management practices on registered dairy farms in Austria. The median number of cows per farm was 20 (interquartile range 13–30). Significant differences regarding farm characteristics and calf management between small and large farms (≤20 vs >20 cows) were present. Only 2.8 % of farmers tested first colostrum quality by use of a hydrometer. Storing frozen colostrum was more prevalent on large farms (80.8 vs 64.2 %). On 85.1 % of the farms, whole milk, including waste milk, was fed to the calves. Milk replacer and waste milk were more often used on large farms. In accordance with similar studies from other countries, calf diarrhoea was indicated as the most prevalent disease. Multivariable logistic regression analysis revealed that herd size was associated with calf diarrhoea and calf respiratory tract disease, with higher risk of disease on large farms. Furthermore, feeding waste milk to the calves was associated with increasing calf diarrhoea incidence on farm. In the final model with calf respiratory tract disease as outcome, respondents from organic farms reported less often a respiratory tract disease incidence of over 10 % compared with conventional farms [odds ratio (OR) 0.40, 95 % confidence interval (CI) 0.21–0.75] and farmers that housed calves individually or in groups after birth significantly reported more often to have an incidence of respiratory tract disease >10 % compared with farms where all calves were housed individually (OR 2.28, 95 % CI 1.16–4.48). CONCLUSION: The results obtained in this study provide an overview on calf management on dairy breeding farms in Austria and may help to further point out areas to be improved on farm. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-015-0134-y) contains supplementary material, which is available to authorized users.",2015 Aug 19,"['Klein-Jöbstl, Daniela', 'Arnholdt, Tim', 'Sturmlechner, Franz', 'Iwersen, Michael', 'Drillich, Marc']",Acta Vet Scand,,,False
d0812df257e4fb4f247f98f53298adea60585674,PMC,Results of an online questionnaire to survey calf management practices on dairy cattle breeding farms in Austria and to estimate differences in disease incidences depending on farm structure and management practices,http://dx.doi.org/10.1186/s13028-015-0134-y,PMC4539725,26282551,CC BY,"BACKGROUND: Calf disease may result in great economic losses. To implement prevention strategies it is important to gain information on management and to point out risk factors. The objective of this internet based survey was to describe calf management practices on registered dairy breeding farms in Austria and to estimate differences in calf disease incidences depending on farm structure and management practices. RESULTS: A total of 1287 questionnaires were finally analysed (response rate 12.2 %). Herd characteristics and regional distribution of farms indicated that this survey gives a good overview on calf management practices on registered dairy farms in Austria. The median number of cows per farm was 20 (interquartile range 13–30). Significant differences regarding farm characteristics and calf management between small and large farms (≤20 vs >20 cows) were present. Only 2.8 % of farmers tested first colostrum quality by use of a hydrometer. Storing frozen colostrum was more prevalent on large farms (80.8 vs 64.2 %). On 85.1 % of the farms, whole milk, including waste milk, was fed to the calves. Milk replacer and waste milk were more often used on large farms. In accordance with similar studies from other countries, calf diarrhoea was indicated as the most prevalent disease. Multivariable logistic regression analysis revealed that herd size was associated with calf diarrhoea and calf respiratory tract disease, with higher risk of disease on large farms. Furthermore, feeding waste milk to the calves was associated with increasing calf diarrhoea incidence on farm. In the final model with calf respiratory tract disease as outcome, respondents from organic farms reported less often a respiratory tract disease incidence of over 10 % compared with conventional farms [odds ratio (OR) 0.40, 95 % confidence interval (CI) 0.21–0.75] and farmers that housed calves individually or in groups after birth significantly reported more often to have an incidence of respiratory tract disease >10 % compared with farms where all calves were housed individually (OR 2.28, 95 % CI 1.16–4.48). CONCLUSION: The results obtained in this study provide an overview on calf management on dairy breeding farms in Austria and may help to further point out areas to be improved on farm. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-015-0134-y) contains supplementary material, which is available to authorized users.",2015 Aug 19,"['Klein-Jöbstl, Daniela', 'Arnholdt, Tim', 'Sturmlechner, Franz', 'Iwersen, Michael', 'Drillich, Marc']",Acta Vet Scand,,,True
384cdcda67c8a385d6a571ba5f9fb09e16d130b5,PMC,Porcine epidemic diarrhea virus inhibits dsRNA-induced interferon-β production in porcine intestinal epithelial cells by blockade of the RIG-I-mediated pathway,http://dx.doi.org/10.1186/s12985-015-0345-x,PMC4539884,26283628,CC BY,"BACKGROUND: The lack of optimal porcine cell lines has severely impeded the study and progress in elucidation of porcine epidemic diarrhea virus (PEDV) pathogenesis. Vero cell, an African green monkey kidney cell line, was often used to isolate and propagate PEDV. Nonetheless, the target cells of PEDV in vivo are intestinal epithelial cells, during infection, intestinal epithelia would be damaged and resulted in digestive disorders. The immune functions of porcine epithelial cells and interactions with other immune cell populations display a number of differences compared to other species. Type I interferon (IFN) plays an important role in antiviral immune response. Limited reports showed that PEDV could inhibit type I interferon production. In this study, porcine small intestinal epithelial cells (IECs), the target cells of PEDV, were used as the infection model in vitro to identify the possible molecular mechanisms of PEDV-inhibition IFN-β production. RESULTS: PEDV not only failed to induce IFN-β expression, but also inhibited dsRNA-mediated IFN-β production in IECs. As the key IFN-β transcription factors, we found that dsRNA-induced activation of IFN regulatory factor 3 (IRF-3) was inhibited after PEDV infection, but not nuclear factor-kappaB (NF-κB). To identify the mechanism of PEDV intervention with dsRNA-mediated IFN-β expression more accurately, the role of individual molecules of RIG-I signaling pathway were investigated. In the upstream of IRF-3, TANK-binding kinase 1 (TBK1)-or inhibitor of κB kinase-ε (IKKε)-mediated IFN-β production was not blocked by PEDV, while RIG-I-and its adapter molecule IFN-β promoter stimulator 1 (IPS-1)-mediated IFN-β production were completely inhibited after PEDV infection. CONCLUSION: Taken together, our data demonstrated for the first time that PEDV infection of its target cell line, IECs, inhibited dsRNA-mediated IFN-β production by blocking the activation of IPS-1 in RIG-I-mediated pathway. Our studies offered new visions in understanding of the interaction between PEDV and host innate immune system.",2015 Aug 18,"['Cao, Liyan', 'Ge, Xuying', 'Gao, Yu', 'Herrler, Georg', 'Ren, Yudong', 'Ren, Xiaofeng', 'Li, Guangxing']",Virol J,,,True
3fe17722a3541e556994dcad8f8d173be7f3ea88,PMC,"Comparative Analysis of Transcriptional Profiles of Adult Schistosoma japonicum from Different Laboratory Animals and the Natural Host, Water Buffalo",http://dx.doi.org/10.1371/journal.pntd.0003993,PMC4540470,26285138,CC BY,"BACKGROUND: Schistosomiasis is one of the most widely distributed parasitic diseases in the world. Schistosoma japonicum, a zoonotic parasite with a wide range of mammalian hosts, is one of the major pathogens of this disease. Although numerous studies on schistosomiasis japonica have been performed using laboratory animal models, systematic comparative analysis of whole-genome expression profiles in parasites from different laboratory animals and nature mammalian hosts is lacking to date. METHODOLOGY/PRINCIPAL FINDINGS: Adult schistosomes were obtained from laboratory animals BALB/c mice, C57BL/6 mice, New Zealand white rabbits and the natural host, water buffaloes. The gene expression profiles of schistosomes from these animals were obtained and compared by genome-wide oligonucleotide microarray analysis. The results revealed that the gene expression profiles of schistosomes from different laboratory animals and buffaloes were highly consistent (r>0.98) genome-wide. Meanwhile, a total of 450 genes were identified to be differentially expressed in schistosomes which can be clustered into six groups. Pathway analysis revealed that these genes were mainly involved in multiple signal transduction pathways, amino acid, energy, nucleotide and lipid metabolism. We also identified a group of 1,540 abundantly and stably expressed gene products in adult worms, including a panel of 179 Schistosoma- or Platyhelminthes-specific genes that may be essential for parasitism and may be regarded as novel potential anti-parasite intervention targets for future research. CONCLUSIONS/SIGNIFICANCE: This study provides a comprehensive database of gene expression profiles of schistosomes derived from different laboratory animals and water buffaloes. An expanded number of genes potentially affecting the development of schistosomes in different animals were identified. These findings lay the foundation for schistosomiasis research in different laboratory animals and natural hosts at the transcriptional level and provide a valuable resource for screening anti-schistosomal intervention targets.",2015 Aug 18,"['Liu, Shuai', 'Zhou, Xiaosu', 'Piao, Xianyu', 'Wu, Chuang', 'Hou, Nan', 'Chen, Qijun']",PLoS Negl Trop Dis,,,True
f2fcc16391f946c99717b63ec9a24e5384aac381,PMC,Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy,http://dx.doi.org/10.1038/srep13028,PMC4541410,26286358,CC BY,"Enfuvirtide (T20), is the first HIV fusion inhibitor approved for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, its clinical application is limited because of short half-life, drug resistance and cross-reactivity with the preexisting antibodies in HIV-infected patients. Using an artificial peptide strategy, we designed a peptide with non-native protein sequence, AP3, which exhibited potent antiviral activity against a broad spectrum of HIV-1 strains, including those resistant to T20, and had remarkably longer in vivo half-life than T20. While the preexisting antibodies in HIV-infected patients significantly suppressed T20’s antiviral activity, these antibodies neither recognized AP3, nor attenuated its anti-HIV-1 activity. Structurally different from T20, AP3 could fold into single-helix and interact with gp41 NHR. The two residues, Met and Thr, at the N-terminus of AP3 form a hook-like structure to stabilize interaction between AP3 and NHR helices. Therefore, AP3 has potential for further development as a new HIV fusion inhibitor with improved antiviral efficacy, resistance profile and pharmacological properties over enfuvirtide. Meanwhile, this study highlighted the advantages of artificially designed peptides, and confirmed that this strategy could be used in developing artificial peptide-based viral fusion inhibitors against HIV and other enveloped viruses.",2015 Aug 19,"['Zhu, Xiaojie', 'Zhu, Yun', 'Ye, Sheng', 'Wang, Qian', 'Xu, Wei', 'Su, Shan', 'Sun, Zhiwu', 'Yu, Fei', 'Liu, Qi', 'Wang, Chao', 'Zhang, Tianhong', 'Zhang, Zhenqing', 'Zhang, Xiaoyan', 'Xu, Jianqing', 'Du, Lanying', 'Liu, Keliang', 'Lu, Lu', 'Zhang, Rongguang', 'Jiang, Shibo']",Sci Rep,,,True
841893d64abe4ad83bfc1bb4542388ad0ad03534,PMC,Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy,http://dx.doi.org/10.1038/srep13028,PMC4541410,26286358,CC BY,"Enfuvirtide (T20), is the first HIV fusion inhibitor approved for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, its clinical application is limited because of short half-life, drug resistance and cross-reactivity with the preexisting antibodies in HIV-infected patients. Using an artificial peptide strategy, we designed a peptide with non-native protein sequence, AP3, which exhibited potent antiviral activity against a broad spectrum of HIV-1 strains, including those resistant to T20, and had remarkably longer in vivo half-life than T20. While the preexisting antibodies in HIV-infected patients significantly suppressed T20’s antiviral activity, these antibodies neither recognized AP3, nor attenuated its anti-HIV-1 activity. Structurally different from T20, AP3 could fold into single-helix and interact with gp41 NHR. The two residues, Met and Thr, at the N-terminus of AP3 form a hook-like structure to stabilize interaction between AP3 and NHR helices. Therefore, AP3 has potential for further development as a new HIV fusion inhibitor with improved antiviral efficacy, resistance profile and pharmacological properties over enfuvirtide. Meanwhile, this study highlighted the advantages of artificially designed peptides, and confirmed that this strategy could be used in developing artificial peptide-based viral fusion inhibitors against HIV and other enveloped viruses.",2015 Aug 19,"['Zhu, Xiaojie', 'Zhu, Yun', 'Ye, Sheng', 'Wang, Qian', 'Xu, Wei', 'Su, Shan', 'Sun, Zhiwu', 'Yu, Fei', 'Liu, Qi', 'Wang, Chao', 'Zhang, Tianhong', 'Zhang, Zhenqing', 'Zhang, Xiaoyan', 'Xu, Jianqing', 'Du, Lanying', 'Liu, Keliang', 'Lu, Lu', 'Zhang, Rongguang', 'Jiang, Shibo']",Sci Rep,,,False
239ea9fe738d669e1d479ec1471d33f1f271a4f8,PMC,"One health, multiple challenges: The inter-species transmission of influenza A virus",http://dx.doi.org/10.1016/j.onehlt.2015.03.001,PMC4542011,26309905,CC BY,"Influenza A viruses are amongst the most challenging viruses that threaten both human and animal health. Influenza A viruses are unique in many ways. Firstly, they are unique in the diversity of host species that they infect. This includes waterfowl (the original reservoir), terrestrial and aquatic poultry, swine, humans, horses, dog, cats, whales, seals and several other mammalian species. Secondly, they are unique in their capacity to evolve and adapt, following crossing the species barrier, in order to replicate and spread to other individuals within the new species. Finally, they are unique in the frequency of inter-species transmission events that occur. Indeed, the consequences of novel influenza virus strain in an immunologically naïve population can be devastating. The problems that influenza A viruses present for human and animal health are numerous. For example, influenza A viruses in humans represent a major economic and disease burden, whilst the poultry industry has suffered colossal damage due to repeated outbreaks of highly pathogenic avian influenza viruses. This review aims to provide a comprehensive overview of influenza A viruses by shedding light on interspecies virus transmission and summarising the current knowledge regarding how influenza viruses can adapt to a new host.",2015 Mar 26,"['Short, Kirsty R.', 'Richard, Mathilde', 'Verhagen, Josanne H.', 'van Riel, Debby', 'Schrauwen, Eefje J.A.', 'van den Brand, Judith M.A.', 'Mänz, Benjamin', 'Bodewes, Rogier', 'Herfst, Sander']",One Health,,,False
7a573001d0844b483871d264983ef4a6d9fde937,PMC,"Improving health aid for a better planet: The planning, monitoring and evaluation tool (PLANET)",http://dx.doi.org/10.7189/jogh.05.020404,PMC4544236,26322228,CC BY,"BACKGROUND: International development assistance for health (DAH) quadrupled between 1990 and 2012, from US$ 5.6 billion to US$ 28.1 billion. This generates an increasing need for transparent and replicable tools that could be used to set investment priorities, monitor the distribution of funding in real time, and evaluate the impact of those investments. METHODS: In this paper we present a methodology that addresses these three challenges. We call this approach PLANET, which stands for planning, monitoring and evaluation tool. Fundamentally, PLANET is based on crowdsourcing approach to obtaining information relevant to deployment of large–scale programs. Information is contributed in real time by a diverse group of participants involved in the program delivery. FINDINGS: PLANET relies on real–time information from three levels of participants in large–scale programs: funders, managers and recipients. At each level, information is solicited to assess five key risks that are most relevant to each level of operations. The risks at the level of funders involve systematic neglect of certain areas, focus on donor’s interests over that of program recipients, ineffective co–ordination between donors, questionable mechanisms of delivery and excessive loss of funding to “middle men”. At the level of managers, the risks are corruption, lack of capacity and/or competence, lack of information and /or communication, undue avoidance of governmental structures / preference to non–governmental organizations and exclusion of local expertise. At the level of primary recipients, the risks are corruption, parallel operations / “verticalization”, misalignment with local priorities and lack of community involvement, issues with ethics, equity and/or acceptability, and low likelihood of sustainability beyond the end of the program’s implementation. INTERPRETATION: PLANET is intended as an additional tool available to policy–makers to prioritize, monitor and evaluate large–scale development programs. In this, it should complement tools such as LiST (for health care/interventions), EQUIST (for health care/interventions) and CHNRI (for health research), which also rely on information from local experts and on local context to set priorities in a transparent, user–friendly, replicable, quantifiable and specific, algorithmic–like manner.",,"['Sridhar, Devi', 'Car, Josip', 'Chopra, Mickey', 'Campbell, Harry', 'Woods, Ngaire', 'Rudan, Igor']",J Glob Health.; 5(2):020404,,,True
a4c922f362c4d59ebe0b890776670e406d9dc985,PMC,"The Fecal Virome of Children with Hand, Foot, and Mouth Disease that Tested PCR Negative for Pathogenic Enteroviruses",http://dx.doi.org/10.1371/journal.pone.0135573,PMC4545796,26288145,CC BY,"Hand, foot, and mouth disease (HFMD) affects infant and young children. A viral metagenomic approach was used to identify the eukaryotic viruses in fecal samples from 29 Thai children with clinical diagnosis of HFMD collected during the 2012 outbreak. These children had previously tested negative by PCR for enterovirus 71 and coxsackievirus A16 and A6. Deep sequencing revealed nine virus families: Picornaviridae, Astroviridae, Parvoviridae, Caliciviridae, Paramyxoviridae, Adenoviridae, Reoviridae, Picobirnaviridae, and Polyomaviridae. The highest number of viral sequences belonged to human rhinovirus C, astrovirus-MLB2, and coxsackievirus A21. Our study provides an overview of virus community and highlights a broad diversity of viruses found in feces from children with HFMD.",2015 Aug 19,"['Linsuwanon, Piyada', 'Poovorawan, Yong', 'Li, Linlin', 'Deng, Xutao', 'Vongpunsawad, Sompong', 'Delwart, Eric']",PLoS One,,,True
850087dea2553c4099418c170742e85fcc4a5feb,PMC,"Concentration, Size Distribution, and Infectivity of Airborne Particles Carrying Swine Viruses",http://dx.doi.org/10.1371/journal.pone.0135675,PMC4545937,26287616,CC BY,"When pathogens become airborne, they travel associated with particles of different size and composition. Particle size determines the distance across which pathogens can be transported, as well as the site of deposition and the survivability of the pathogen. Despite the importance of this information, the size distribution of particles bearing viruses emitted by infectious animals remains unknown. In this study we characterized the concentration and size distribution of inhalable particles that transport influenza A virus (IAV), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine epidemic diarrhea virus (PEDV) generated by acutely infected pigs and assessed virus viability for each particle size range. Aerosols from experimentally infected pigs were sampled for 24 days using an Andersen cascade impactor able to separate particles by size (ranging from 0.4 to 10 micrometer (μm) in diameter). Air samples collected for the first 9, 20 and the last 3 days of the study were analyzed for IAV, PRRSV and PEDV, respectively, using quantitative reverse transcription polymerase chain reaction (RT-PCR) and quantified as geometric mean copies/m(3) within each size range. IAV was detected in all particle size ranges in quantities ranging from 5.5x10(2) (in particles ranging from 1.1 to 2.1μm) to 4.3x10(5) RNA copies/m(3) in the largest particles (9.0–10.0μm). PRRSV was detected in all size ranges except particles between 0.7 and 2.1μm in quantities ranging from 6x10(2) (0.4–0.7μm) to 5.1x10(4) RNA copies/m(3) (9.0–10.0μm). PEDV, an enteric virus, was detected in all particle sizes and in higher quantities than IAV and PRRSV (p < 0.0001) ranging from 1.3x10(6) (0.4–0.7μm) to 3.5x10(8) RNA copies/m(3) (9.0–10.0μm). Infectious status was demonstrated for the 3 viruses, and in the case of IAV and PRRSV, viruses were isolated from particles larger than 2.1μm. In summary, our results indicated that airborne PEDV, IAV and PRRSV can be found in a wide range of particle sizes. However, virus viability is particle size dependent.",2015 Aug 19,"['Alonso, Carmen', 'Raynor, Peter C.', 'Davies, Peter R.', 'Torremorell, Montserrat']",PLoS One,,,True
78646cec8be584199a96490a43bf47b2fd542f63,PMC,Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study,http://dx.doi.org/10.1371/journal.pone.0134928,PMC4546056,26287532,CC BY,"OBJECTIVE: Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status. METHODS: This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK. RESULTS: Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively. CONCLUSIONS: Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.",2015 Aug 19,"['Pockett, Rhys D.', 'Watkins, John', 'McEwan, Phil', 'Meier, Genevieve']",PLoS One,,,True
555559ac51210f5ee896ad5d45a6790d52a3e4d1,PMC,Determinants of emergency response responsibility perceptions in the local public health workforce after China’s health sector restructuring,http://dx.doi.org/10.1186/s12913-015-1003-0,PMC4546225,26293247,CC BY,"BACKGROUND: Local health departments are the backbone of public health emergency (PHE) response plans. The front line of emergency response preparedness is people. Role perceptions of individual staff members of a given organization strongly affect response probability and performance. Therefore, the aim of this study was to determine local public health employees’ perceptions of emergency response responsibilities, identify factors that influence their perception, and indicate the challenges and bottlenecks of PHE response in the Health Inspection Institution (HII) after its separation from China’s multiple Centers for Disease Control and Prevention (CDC). METHODS: We used a stratified randomized sample survey to examine HII workers’ knowledge of their own duties concerning PHE response in 17 facilities in Heilongjiang, a province in northeastern China. Data were collected from May to July 2010 using a 9-item combined question inquiring about the workers’ statutory duties. RESULTS: Of 348 administered surveys, 309 were returned for an overall response rate of 88.8 %. Overall, the correct recognition rate of PHE responsibilities was low. Some HII workers were confused about their responsibilities required by law, regulations, and emergency response plans. A quarter of all the respondents had the lowest knowledge for PHE responsibilities. Factors influencing their perceptions of responsibilities were department, work experience in a CDC, and PHE response experience. CONCLUSIONS: To improve preparedness for a PHE, efforts are needed to train, support, and monitor the workers’ knowledge and competencies in PHEs as part of an organizational change; the worker’s knowledge of their responsibilities should be measured and used as an indicator of preparedness for a PHE, and training should be undertaken where there are deficiencies. Management should also encourage workers in the departments of food hygiene/school health surveillance to be more involved in PHE preparedness and response issues.",2015 Aug 21,"['Jiao, Mingli', 'Ning, Ning', 'Wu, Qunhong', 'Peters, David H.', 'Hao, Yanhua', 'Li, Ye', 'Wei, Xingang', 'Kang, Zheng']",BMC Health Serv Res,,,True
fad38d4f310922f5af4326b319cfaf1eb8f70282,PMC,"Japanese Encephalitis in Assam, India: Need to Increase Healthcare Workers’ Understanding to Improve Health Care",http://dx.doi.org/10.1371/journal.pone.0135767,PMC4546657,26296212,CC BY,"INTRODUCTION: Japanese encephalitis (JE) is a major cause of high morbidity and mortality in several states across India. However, in 2014, a sharp rise was observed in the number of cases of JE in north-eastern Assam state, and 51% of the total cases of JE in India were reported from the Assam in the same year. In this regard, a study was conducted to evaluate the knowledge and attitudes of healthcare workers in Darrang, a district of Assam highly affected by JE. METHODS: A cross sectional study was conducted for 2 months among HCWs in the major district hospital of Darrang, Assam. A pre-tested, self-administered questionnaire was used to collect data from the participants. Convenience sampling approach was used to collect data from different departments of the hospitals. Descriptive and logistic regression analyses were used to express the results. RESULTS: The knowledge of HCWs regarding JE was poor with a mean knowledge score of 11.02±2.39 (out of 17), while their attitudes were positive with a mean attitudes score of 43.16± 2.47 (ranging from 13 to 52). Overall, 40.4% and 74.3% of participants demonstrated good knowledge and positive attitudes respectively. Cut-off score for good knowledge and positive attitudes toward JE was set as ≥12 and >40 respectively. Older participants (40–49 years) and experienced workers (>10 years) were significantly associated with good knowledge as compared to their referent group (p<0.05), while knowledge of nurses and other orderlies were significantly lower than physicians (p<0.01). Similar factors were associated with the positive attitudes of the participants with the exception of experience. Television was the major source of information regarding JE reported by HCWs (79%). CONCLUSION: Although the knowledge was not optimized, HCWs exhibited positive attitudes towards JE. Future research is required to design, implement and evaluate interventions to improve the knowledge of JE among HCWs.",2015 Aug 21,"['Ahmad, Akram', 'Khan, Muhammad Umair', 'Gogoi, Lakhya Jyoti', 'Kalita, Manabendra', 'Sikdar, Atul Prasad', 'Pandey, Sureshwar', 'Dhingra, Sameer']",PLoS One,,,True
4c4dd391e165ce712cb8871ce3082927bbf21ec9,PMC,Detection of Cytomegalovirus Antibodies Using a Biosensor Based on Imaging Ellipsometry,http://dx.doi.org/10.1371/journal.pone.0136253,PMC4546680,26295458,CC BY,"BACKGROUND: Cytomegalovirus (CMV) is the most common infectious cause of mental disability in newborns in developed countries. There is an urgent need to establish an early detection and high-throughput screening method for CMV infection using portable detection devices. METHODS: An antibody analysis method is reported for the detection and identification of CMV antibodies in serum using a biosensor based on high spatial resolution imaging ellipsometry (BIE). CMV antigen (CMV-3A) was immobilized on silicon wafers and used to capture CMV antibodies in serum. An antibody against human immunoglobulin G (anti-IgG) was used to confirm the IgG antibody against CMV captured by the CMV-3A. RESULTS: Our results show that this assay is rapid and specific for the identification of IgG antibody against CMV. Further, patient serum was quantitatively assessed using the standard curve method, and the quantitative results were in agreement with the enzyme-linked immunosorbent assay. The CMV antibody detection sensitivity of BIE reached 0.01 IU/mL. CONCLUSIONS: This novel biosensor may be a valuable diagnostic tool for analysis of IgG antibody against CMV during CMV infection screening.",2015 Aug 21,"['Sun, Hongliu', 'Qi, Cai', 'Niu, Yu', 'Kang, Tengfei', 'Wei, Yongxin', 'Jin, Gang', 'Dong, Xianzhi', 'Wang, Chunhua', 'Zhu, Wei']",PLoS One,,,True
7aea98cf7d30beea6043c5e62be3dafce08bdc0e,PMC,Non-immune immunoglobulins shield Schistosoma japonicum from host immunorecognition,http://dx.doi.org/10.1038/srep13434,PMC4547136,26299686,CC BY,"Schistosomiasis is a major human parasitic disease with a global impact. Schistosoma japonicum, the most difficult to control, can survive within host veins for decades. Mechanisms of immune evasion by the parasite, including antigenic variation and surface masking, have been implicated but not well defined. In this study, we defined the immunoglobulin-binding proteomes of S. japonicum using human IgG, IgM, and IgE as the molecular bait for affinity purification, followed by protein identification by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Several proteins situated at the tegument of S. japonicum were able to nonselectively bind to the Fc domain of host immunoglobulins, indicating a mechanism for the avoidance of host immune attachment and recognition. The profile of the immunoglobulin-binding proteomes provides further clues for immune evasion mechanisms adopted by S. japonicum.",2015 Aug 24,"['Wu, Chuang', 'Hou, Nan', 'Piao, Xianyu', 'Liu, Shuai', 'Cai, Pengfei', 'Xiao, Yan', 'Chen, Qijun']",Sci Rep,,,True
634c299b334104ab3b8be50713f7521b9eb06d4a,PMC,Non-immune immunoglobulins shield Schistosoma japonicum from host immunorecognition,http://dx.doi.org/10.1038/srep13434,PMC4547136,26299686,CC BY,"Schistosomiasis is a major human parasitic disease with a global impact. Schistosoma japonicum, the most difficult to control, can survive within host veins for decades. Mechanisms of immune evasion by the parasite, including antigenic variation and surface masking, have been implicated but not well defined. In this study, we defined the immunoglobulin-binding proteomes of S. japonicum using human IgG, IgM, and IgE as the molecular bait for affinity purification, followed by protein identification by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Several proteins situated at the tegument of S. japonicum were able to nonselectively bind to the Fc domain of host immunoglobulins, indicating a mechanism for the avoidance of host immune attachment and recognition. The profile of the immunoglobulin-binding proteomes provides further clues for immune evasion mechanisms adopted by S. japonicum.",2015 Aug 24,"['Wu, Chuang', 'Hou, Nan', 'Piao, Xianyu', 'Liu, Shuai', 'Cai, Pengfei', 'Xiao, Yan', 'Chen, Qijun']",Sci Rep,,,False
1d720a06cad9b69f7f45a4e7549142738114287e,PMC,Chicken egg yolk antibodies (IgY) as non-antibiotic production enhancers for use in swine production: a review,http://dx.doi.org/10.1186/s40104-015-0038-8,PMC4549021,26309735,CC BY,"In recent years, the use of in-feed antibiotics for growth and disease prevention in livestock production has been under severe scrutiny. The use and misuse of in-feed antibiotics has led to problems with drug residues in animal products and increased bacterial resistance. Chicken egg yolk antibodies (IgY) have attracted considerable attention as an alternative to antibiotics to maintain swine health and performance. Oral administration of IgY possesses many advantages over mammalian IgG such as cost-effectiveness, convenience and high yield. This review presents an overview of the potential to use IgY immunotherapy for the prevention and treatment of swine diarrhea diseases and speculates on the future of IgY technology. Included are a review of the potential applications of IgY in the control of enteric infections of either bacterial or viral origin such as enterotoxigenic Escherichia coli, Salmonella spp., rotavirus, porcine transmissible gastroenteritis virus, and porcine epidemic diarrhea virus. Some potential obstacles to the adoption of IgY technology are also discussed.",2015 Aug 25,"['Li, Xiaoyu', 'Wang, Lili', 'Zhen, Yuhong', 'Li, Shuying', 'Xu, Yongping']",J Anim Sci Biotechnol,,,True
c3b1f22e16b5f9f5961e135d3a79eaad57061aa2,PMC,Social determinants of health inequalities: towards a theoretical perspective using systems science,http://dx.doi.org/10.1186/s12939-015-0205-8,PMC4549102,26303914,CC BY,"A systems approach offers a novel conceptualization to natural and social systems. In recent years, this has led to perceiving population health outcomes as an emergent property of a dynamic and open, complex adaptive system. The current paper explores these themes further and applies the principles of systems approach and complexity science (i.e. systems science) to conceptualize social determinants of health inequalities. The conceptualization can be done in two steps: viewing health inequalities from a systems approach and extending it to include complexity science. Systems approach views health inequalities as patterns within the larger rubric of other facets of the human condition, such as educational outcomes and economic development. This anlysis requires more sophisticated models such as systems dynamic models. An extension of the approach is to view systems as complex adaptive systems, i.e. systems that are 'open' and adapt to the environment. They consist of dynamic adapting subsystems that exhibit non-linear interactions, while being 'open' to a similarly dynamic environment of interconnected systems. They exhibit emergent properties that cannot be estimated with precision by using the known interactions among its components (such as economic development, political freedom, health system, culture etc.). Different combinations of the same bundle of factors or determinants give rise to similar patterns or outcomes (i.e. property of convergence), and minor variations in the initial condition could give rise to widely divergent outcomes. Novel approaches using computer simulation models (e.g. agent-based models) would shed light on possible mechanisms as to how factors or determinants interact and lead to emergent patterns of health inequalities of populations.",2015 Aug 25,"Jayasinghe, Saroj",Int J Equity Health,,,True
d889f70c1e55668de7d33d59e76f3daf7cc8a28b,PMC,Proteomics-Based Characterization of the Humoral Immune Response in Sporotrichosis: Toward Discovery of Potential Diagnostic and Vaccine Antigens,http://dx.doi.org/10.1371/journal.pntd.0004016,PMC4549111,26305691,CC BY,"BACKGROUND: Sporothrix schenckii and associated species are agents of human and animal sporotrichosis that cause large sapronoses and zoonoses worldwide. Epidemiological surveillance has highlighted an overwhelming occurrence of the highly pathogenic fungus Sporothrix brasiliensis during feline outbreaks, leading to massive transmissions to humans. Early diagnosis of feline sporotrichosis by demonstrating the presence of a surrogate marker of infection can have a key role for selecting appropriate disease control measures and minimizing zoonotic transmission to humans. METHODOLOGY: We explored the presence and diversity of serum antibodies (IgG) specific against Sporothrix antigens in cats with sporotrichosis and evaluated the utility of these antibodies for serodiagnosis. Antigen profiling included protein extracts from the closest known relatives S. brasiliensis and S. schenckii. Enzyme-linked immunosorbent assays and immunoblotting enabled us to characterize the major antigens of feline sporotrichosis from sera from cats with sporotrichosis (n = 49), healthy cats (n = 19), and cats with other diseases (n = 20). PRINCIPAL FINDINGS: Enzyme-linked immunosorbent assay-based quantitation of anti-Sporothrix IgG exhibited high sensitivity and specificity in cats with sporotrichosis (area under the curve, 1.0; 95% confidence interval, 0.94–1; P<0.0001) versus controls. The two sets of Sporothrix antigens were remarkably cross-reactive, supporting the hypothesis that antigenic epitopes may be conserved among closely related agents. One-dimensional immunoblotting indicated that 3-carboxymuconate cyclase (a 60-kDa protein in S. brasiliensis and a 70-kDa protein in S. schenckii) is the immunodominant antigen in feline sporotrichosis. Two-dimensional immunoblotting revealed six IgG-reactive isoforms of gp60 in the S. brasiliensis proteome, similar to the humoral response found in human sporotrichosis. CONCLUSIONS: A convergent IgG-response in various hosts (mice, cats, and humans) has important implications for our understanding of the coevolution of Sporothrix and its warm-blooded hosts. We propose that 3-carboxymuconate cyclase has potential for the serological diagnosis of sporotrichosis and as target for the development of an effective multi-species vaccine against sporotrichosis in animals and humans.",2015 Aug 25,"['Rodrigues, Anderson Messias', 'Fernandes, Geisa Ferreira', 'Araujo, Leticia Mendes', 'Della Terra, Paula Portella', 'dos Santos, Priscila Oliveira', 'Pereira, Sandro Antonio', 'Schubach, Tânia Maria Pacheco', 'Burger, Eva', 'Lopes-Bezerra, Leila Maria', 'de Camargo, Zoilo Pires']",PLoS Negl Trop Dis,,,True
8afc50240bb49d3427d515da43bb2ca16975daf8,PMC,Proteomics-Based Characterization of the Humoral Immune Response in Sporotrichosis: Toward Discovery of Potential Diagnostic and Vaccine Antigens,http://dx.doi.org/10.1371/journal.pntd.0004016,PMC4549111,26305691,CC BY,"BACKGROUND: Sporothrix schenckii and associated species are agents of human and animal sporotrichosis that cause large sapronoses and zoonoses worldwide. Epidemiological surveillance has highlighted an overwhelming occurrence of the highly pathogenic fungus Sporothrix brasiliensis during feline outbreaks, leading to massive transmissions to humans. Early diagnosis of feline sporotrichosis by demonstrating the presence of a surrogate marker of infection can have a key role for selecting appropriate disease control measures and minimizing zoonotic transmission to humans. METHODOLOGY: We explored the presence and diversity of serum antibodies (IgG) specific against Sporothrix antigens in cats with sporotrichosis and evaluated the utility of these antibodies for serodiagnosis. Antigen profiling included protein extracts from the closest known relatives S. brasiliensis and S. schenckii. Enzyme-linked immunosorbent assays and immunoblotting enabled us to characterize the major antigens of feline sporotrichosis from sera from cats with sporotrichosis (n = 49), healthy cats (n = 19), and cats with other diseases (n = 20). PRINCIPAL FINDINGS: Enzyme-linked immunosorbent assay-based quantitation of anti-Sporothrix IgG exhibited high sensitivity and specificity in cats with sporotrichosis (area under the curve, 1.0; 95% confidence interval, 0.94–1; P<0.0001) versus controls. The two sets of Sporothrix antigens were remarkably cross-reactive, supporting the hypothesis that antigenic epitopes may be conserved among closely related agents. One-dimensional immunoblotting indicated that 3-carboxymuconate cyclase (a 60-kDa protein in S. brasiliensis and a 70-kDa protein in S. schenckii) is the immunodominant antigen in feline sporotrichosis. Two-dimensional immunoblotting revealed six IgG-reactive isoforms of gp60 in the S. brasiliensis proteome, similar to the humoral response found in human sporotrichosis. CONCLUSIONS: A convergent IgG-response in various hosts (mice, cats, and humans) has important implications for our understanding of the coevolution of Sporothrix and its warm-blooded hosts. We propose that 3-carboxymuconate cyclase has potential for the serological diagnosis of sporotrichosis and as target for the development of an effective multi-species vaccine against sporotrichosis in animals and humans.",2015 Aug 25,"['Rodrigues, Anderson Messias', 'Fernandes, Geisa Ferreira', 'Araujo, Leticia Mendes', 'Della Terra, Paula Portella', 'dos Santos, Priscila Oliveira', 'Pereira, Sandro Antonio', 'Schubach, Tânia Maria Pacheco', 'Burger, Eva', 'Lopes-Bezerra, Leila Maria', 'de Camargo, Zoilo Pires']",PLoS Negl Trop Dis,,,False
d38f954f1b3937ead02257e75454dd9ad2ec0ce6,PMC,"An evaluation of psychological distress and social support of survivors and contacts of Ebola virus disease infection and their relatives in Lagos, Nigeria: a cross sectional study − 2014",http://dx.doi.org/10.1186/s12889-015-2167-6,PMC4550041,26307047,CC BY,"BACKGROUND: By September 2014, an outbreak of Ebola Viral Disease (EVD) in West African countries of Guinea, Liberia, Sierra Leone, Senegal and Nigeria, had recorded over 4500 and 2200 probable or confirmed cases and deaths respectively. EVD, an emerging infectious disease, can create fear and panic among patients, contacts and relatives, which could be a risk factor for psychological distress. Psychological distress among this subgroup could have public health implication for control of EVD, because of potential effects on patient management and contact tracing. We determined the Prevalence, pattern and factors associated with psychological distress among survivors and contacts of EVD and their relatives. METHODS: In a descriptive cross sectional study, we used General Health Questionnaire to assess psychological distress and Oslo Social Support Scale to assess social support among 117 participants who survived EVD, listed as EVD contacts or their relatives at Ebola Emergency Operation Center in Lagos, Nigeria. Factors associated with psychological distress were determined using chi square/odds ratio and adjusted odds ratio. RESULTS: The mean age and standard deviation of participants was 34 +/ - 9.6 years. Of 117 participants, 78 (66.7 %) were females, 77 (65.8 %) had a tertiary education and 45 (38.5 %) were health workers. Most frequently occurring psychological distress were inability to concentrate (37.6 %) and loss of sleep over worry (33.3 %). Losing a relation to EVD outbreak (OR = 6.0, 95 % CI, 1.2–32.9) was significantly associated with feeling unhappy or depressed while being a health worker was protective (OR = 0.4, 95 % CI, 0.2–0.9). Adjusted Odds Ratio (AOR) showed losing a relation (AOR = 5.7, 95 % CI, 1.2–28.0) was a predictor of “feeling unhappy or depressed”, loss of a relation (AOR = 10.1, 95 % CI, 1.7–60.7) was a predictor of inability to concentrate. CONCLUSIONS: Survivors and contacts of EVD and their relations develop psychological distress. Development of psychological distress could be predicted by loss of family member. It is recommended that psychiatrists and other mental health specialists be part of case management teams. The clinical teams managing EVD patients should be trained on recognition of common psychological distress among patients. A mental health specialist should review contacts being monitored for EVD for psychological distress or disorders.",2015 Aug 27,"['Mohammed, Abdulaziz', 'Sheikh, Taiwo Lateef', 'Gidado, Saheed', 'Poggensee, Gabriele', 'Nguku, Patrick', 'Olayinka, Adebola', 'Ohuabunwo, Chima', 'Waziri, Ndadilnasiya', 'Shuaib, Faisal', 'Adeyemi, Joseph', 'Uzoma, Ogbonna', 'Ahmed, Abubakar', 'Doherty, Funmi', 'Nyanti, Sarah Beysolow', 'Nzuki, Charles Kyalo', 'Nasidi, Abdulsalami', 'Oyemakinde, Akin', 'Oguntimehin, Olukayode', 'Abdus-salam, Ismail Adeshina', 'Obiako, Reginald O.']",BMC Public Health,,,True
f2e06c174008ed721d0a244309601c9923548901,PMC,"Genomic analysis of codon usage shows influence of mutation pressure, natural selection, and host features on Marburg virus evolution",http://dx.doi.org/10.1186/s12862-015-0456-4,PMC4550055,26306510,CC BY,"BACKGROUND: The Marburg virus (MARV) has a negative-sense single-stranded RNA genome, belongs to the family Filoviridae, and is responsible for several outbreaks of highly fatal hemorrhagic fever. Codon usage patterns of viruses reflect a series of evolutionary changes that enable viruses to shape their survival rates and fitness toward the external environment and, most importantly, their hosts. To understand the evolution of MARV at the codon level, we report a comprehensive analysis of synonymous codon usage patterns in MARV genomes. Multiple codon analysis approaches and statistical methods were performed to determine overall codon usage patterns, biases in codon usage, and influence of various factors, including mutation pressure, natural selection, and its two hosts, Homo sapiens and Rousettus aegyptiacus. RESULTS: Nucleotide composition and relative synonymous codon usage (RSCU) analysis revealed that MARV shows mutation bias and prefers U- and A-ended codons to code amino acids. Effective number of codons analysis indicated that overall codon usage among MARV genomes is slightly biased. The Parity Rule 2 plot analysis showed that GC and AU nucleotides were not used proportionally which accounts for the presence of natural selection. Codon usage patterns of MARV were also found to be influenced by its hosts. This indicates that MARV have evolved codon usage patterns that are specific to both of its hosts. Moreover, selection pressure from R. aegyptiacus on the MARV RSCU patterns was found to be dominant compared with that from H. sapiens. Overall, mutation pressure was found to be the most important and dominant force that shapes codon usage patterns in MARV. CONCLUSIONS: To our knowledge, this is the first detailed codon usage analysis of MARV and extends our understanding of the mechanisms that contribute to codon usage and evolution of MARV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-015-0456-4) contains supplementary material, which is available to authorized users.",2015 Aug 26,"['Nasrullah, Izza', 'Butt, Azeem M', 'Tahir, Shifa', 'Idrees, Muhammad', 'Tong, Yigang']",BMC Evol Biol,,,True
5a89b93e5c8c6fb1352d9881f6ca6b592ef4af30,PMC,Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting,http://dx.doi.org/10.1038/srep13476,PMC4550849,26310922,CC BY,"A longstanding and still-increasing threat to the effective treatment of infectious diseases is resistance to antimicrobial countermeasures. Potentially, the targeting of host proteins and pathways essential for the detrimental effects of pathogens offers an approach that may discover broad-spectrum anti-pathogen countermeasures and circumvent the effects of pathogen mutations leading to resistance. Here we report implementation of a strategy for discovering broad-spectrum host-oriented therapies against multiple pathogenic agents by multiplex screening of drugs for protection against the detrimental effects of multiple pathogens, identification of host cell pathways inhibited by the drug, and screening for effects of the agent on other pathogens exploiting the same pathway. We show that a clinically used antimalarial drug, Amodiaquine, discovered by this strategy, protects host cells against infection by multiple toxins and viruses by inhibiting host cathepsin B. Our results reveal the practicality of discovering broadly acting anti-pathogen countermeasures that target host proteins exploited by pathogens.",2015 Aug 27,"['Zilbermintz, Leeor', 'Leonardi, William', 'Jeong, Sun-Young', 'Sjodt, Megan', 'McComb, Ryan', 'Ho, Chi-Lee C.', 'Retterer, Cary', 'Gharaibeh, Dima', 'Zamani, Rouzbeh', 'Soloveva, Veronica', 'Bavari, Sina', 'Levitin, Anastasia', 'West, Joel', 'Bradley, Kenneth A.', 'Clubb, Robert T.', 'Cohen, Stanley N.', 'Gupta, Vivek', 'Martchenko, Mikhail']",Sci Rep,,,True
0d354b208fdfa2806bf33fd03e940e057b339de5,PMC,Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting,http://dx.doi.org/10.1038/srep13476,PMC4550849,26310922,CC BY,"A longstanding and still-increasing threat to the effective treatment of infectious diseases is resistance to antimicrobial countermeasures. Potentially, the targeting of host proteins and pathways essential for the detrimental effects of pathogens offers an approach that may discover broad-spectrum anti-pathogen countermeasures and circumvent the effects of pathogen mutations leading to resistance. Here we report implementation of a strategy for discovering broad-spectrum host-oriented therapies against multiple pathogenic agents by multiplex screening of drugs for protection against the detrimental effects of multiple pathogens, identification of host cell pathways inhibited by the drug, and screening for effects of the agent on other pathogens exploiting the same pathway. We show that a clinically used antimalarial drug, Amodiaquine, discovered by this strategy, protects host cells against infection by multiple toxins and viruses by inhibiting host cathepsin B. Our results reveal the practicality of discovering broadly acting anti-pathogen countermeasures that target host proteins exploited by pathogens.",2015 Aug 27,"['Zilbermintz, Leeor', 'Leonardi, William', 'Jeong, Sun-Young', 'Sjodt, Megan', 'McComb, Ryan', 'Ho, Chi-Lee C.', 'Retterer, Cary', 'Gharaibeh, Dima', 'Zamani, Rouzbeh', 'Soloveva, Veronica', 'Bavari, Sina', 'Levitin, Anastasia', 'West, Joel', 'Bradley, Kenneth A.', 'Clubb, Robert T.', 'Cohen, Stanley N.', 'Gupta, Vivek', 'Martchenko, Mikhail']",Sci Rep,,,True
77361db3ae17729e18971ae8641a20691e44afab,PMC,Therapeutic Immunoglobulin Selected for High Antibody Titer to RSV also Contains High Antibody Titers to Other Respiratory Viruses,http://dx.doi.org/10.3389/fimmu.2015.00431,PMC4551866,26379667,CC BY,"Specific antibodies against infections most relevant to patients with primary immunodeficiency diseases are not routinely evaluated in commercial polyclonal immunoglobulin preparations. A polyclonal immunoglobulin prepared from plasma of donors having high neutralizing antibody titers to respiratory syncytial virus (RSV) was studied for the presence of antibody titers against seven additional respiratory viruses. While donors were not selected for antibody titers other than against RSV, the immunoglobulin preparation had significantly higher titers to 6 of 7 viruses compared to those present in 10 commercially available therapeutic immunoglobulin products (p ≤ 0.01 to p ≤ 0.001). To consider this as a donor-specific attribute, 20 random donor plasma samples were studied individually and identified a significant correlation between the RSV antibody titer and other respiratory virus titers: donors with high RSV titers were more likely to have higher titers to other respiratory viruses. These findings suggest either some humoral antiviral response bias or more frequent viral exposure of certain individuals.",2015 Aug 28,"['Orange, Jordan S.', 'Du, Wei', 'Falsey, Ann R.']",Front Immunol,,,True
84dfdd13ab7bf0544b5939a86b0c24b9a06e9700,PMC,The Role of Dipeptidyl Peptidase – 4 Inhibitors in Diabetic Kidney Disease,http://dx.doi.org/10.3389/fimmu.2015.00443,PMC4551869,26379674,CC BY,"Despite major advances in the understanding of the molecular mechanisms that underpin the development of diabetic kidney disease, current best practice still leaves a significant proportion of patients with end-stage kidney disease requiring renal replacement therapy. This is on a background of an increasing diabetes epidemic worldwide. Although kidney failure is a major cause of morbidity the main cause of death remains cardiovascular in nature. Hence, diabetic therapies which are both “cardio-renal” protective seem the logical way forward. In this review, we discuss the dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4inh), which are glucose-lowering agents used clinically and their role in diabetic kidney disease with specific focus on renoprotection and surrogate markers of cardiovascular disease. We highlight the novel pleiotropic effects of DPP4 that make it an attractive additional target to combat the fibrotic and inflammatory pathways in diabetic kidney disease and also discuss the current literature on the cardiovascular safety profile of DPP4inh. Clearly, these observed renoprotective effects will need to be confirmed by clinical trials to determine whether they translate into beneficial effects to patients with diabetes.",2015 Aug 28,"['Panchapakesan, Usha', 'Pollock, Carol']",Front Immunol,,,True
8a387a670706c2009e6c5e7a39c112a9e645f963,PMC,Shedding of Infectious Borna Disease Virus-1 in Living Bicolored White-Toothed Shrews,http://dx.doi.org/10.1371/journal.pone.0137018,PMC4552160,26313904,CC BY,"BACKGROUND: Many RNA viruses arise from animal reservoirs, namely bats, rodents and insectivores but mechanisms of virus maintenance and transmission still need to be addressed. The bicolored white-toothed shrew (Crocidura leucodon) has recently been identified as reservoir of the neurotropic Borna disease virus 1 (BoDV-1). PRINCIPAL FINDINGS: Six out of eleven wild living bicoloured white-toothed shrews were trapped and revealed to be naturally infected with BoDV-1. All shrews were monitored in captivity in a long-term study over a time period up to 600 days that differed between the individual shrews. Interestingly, all six animals showed an asymptomatic course of infection despite virus shedding via various routes indicating a highly adapted host-pathogen interaction. Infectious virus and viral RNA were demonstrated in saliva, urine, skin swabs, lacrimal fluid and faeces, both during the first 8 weeks of the investigation period and for long time shedding after more than 250 days in captivity. CONCLUSIONS: The various ways of shedding ensure successful virus maintenance in the reservoir population but also transmission to accidental hosts such as horses and sheep. Naturally BoDV-1-infected living shrews serve as excellent tool to unravel host and pathogen factors responsible for persistent viral co-existence in reservoir species while maintaining their physiological integrity despite high viral load in many organ systems.",2015 Aug 27,"['Nobach, Daniel', 'Bourg, Manon', 'Herzog, Sibylle', 'Lange-Herbst, Hildburg', 'Encarnação, Jorge A.', 'Eickmann, Markus', 'Herden, Christiane']",PLoS One,,,True
01cad955f2c6d1373797935f0b33b23d386b26bf,PMC,Shedding of Infectious Borna Disease Virus-1 in Living Bicolored White-Toothed Shrews,http://dx.doi.org/10.1371/journal.pone.0137018,PMC4552160,26313904,CC BY,"BACKGROUND: Many RNA viruses arise from animal reservoirs, namely bats, rodents and insectivores but mechanisms of virus maintenance and transmission still need to be addressed. The bicolored white-toothed shrew (Crocidura leucodon) has recently been identified as reservoir of the neurotropic Borna disease virus 1 (BoDV-1). PRINCIPAL FINDINGS: Six out of eleven wild living bicoloured white-toothed shrews were trapped and revealed to be naturally infected with BoDV-1. All shrews were monitored in captivity in a long-term study over a time period up to 600 days that differed between the individual shrews. Interestingly, all six animals showed an asymptomatic course of infection despite virus shedding via various routes indicating a highly adapted host-pathogen interaction. Infectious virus and viral RNA were demonstrated in saliva, urine, skin swabs, lacrimal fluid and faeces, both during the first 8 weeks of the investigation period and for long time shedding after more than 250 days in captivity. CONCLUSIONS: The various ways of shedding ensure successful virus maintenance in the reservoir population but also transmission to accidental hosts such as horses and sheep. Naturally BoDV-1-infected living shrews serve as excellent tool to unravel host and pathogen factors responsible for persistent viral co-existence in reservoir species while maintaining their physiological integrity despite high viral load in many organ systems.",2015 Aug 27,"['Nobach, Daniel', 'Bourg, Manon', 'Herzog, Sibylle', 'Lange-Herbst, Hildburg', 'Encarnação, Jorge A.', 'Eickmann, Markus', 'Herden, Christiane']",PLoS One,,,False
dec1d801c2d5a971207df424ede4b1d65267b212,PMC,Transcriptional slippage in the positive-sense RNA virus family Potyviridae,http://dx.doi.org/10.15252/embr.201540509,PMC4552492,26113364,CC BY,"The family Potyviridae encompasses ∼30% of plant viruses and is responsible for significant economic losses worldwide. Recently, a small overlapping coding sequence, termed pipo, was found to be conserved in the genomes of all potyvirids. PIPO is expressed as part of a frameshift protein, P3N-PIPO, which is essential for virus cell-to-cell movement. However, the frameshift expression mechanism has hitherto remained unknown. Here, we demonstrate that transcriptional slippage, specific to the viral RNA polymerase, results in a population of transcripts with an additional “A” inserted within a highly conserved GAAAAAA sequence, thus enabling expression of P3N-PIPO. The slippage efficiency is ∼2% in Turnip mosaic virus and slippage is inhibited by mutations in the GAAAAAA sequence. While utilization of transcriptional slippage is well known in negative-sense RNA viruses such as Ebola, mumps and measles, to our knowledge this is the first report of its widespread utilization for gene expression in positive-sense RNA viruses.",2015 Aug 25,"['Olspert, Allan', 'Chung, Betty Y-W', 'Atkins, John F', 'Carr, John P', 'Firth, Andrew E']",EMBO Rep,,,True
8ec5d7c229660267edbf9932e5ebe5edf0cea6fc,PMC,Transcriptional slippage in the positive-sense RNA virus family Potyviridae,http://dx.doi.org/10.15252/embr.201540509,PMC4552492,26113364,CC BY,"The family Potyviridae encompasses ∼30% of plant viruses and is responsible for significant economic losses worldwide. Recently, a small overlapping coding sequence, termed pipo, was found to be conserved in the genomes of all potyvirids. PIPO is expressed as part of a frameshift protein, P3N-PIPO, which is essential for virus cell-to-cell movement. However, the frameshift expression mechanism has hitherto remained unknown. Here, we demonstrate that transcriptional slippage, specific to the viral RNA polymerase, results in a population of transcripts with an additional “A” inserted within a highly conserved GAAAAAA sequence, thus enabling expression of P3N-PIPO. The slippage efficiency is ∼2% in Turnip mosaic virus and slippage is inhibited by mutations in the GAAAAAA sequence. While utilization of transcriptional slippage is well known in negative-sense RNA viruses such as Ebola, mumps and measles, to our knowledge this is the first report of its widespread utilization for gene expression in positive-sense RNA viruses.",2015 Aug 25,"['Olspert, Allan', 'Chung, Betty Y-W', 'Atkins, John F', 'Carr, John P', 'Firth, Andrew E']",EMBO Rep,,,False
f19eac518ac044aff2085587409e8b6d2a02aa99,PMC,Transcriptional slippage in the positive-sense RNA virus family Potyviridae,http://dx.doi.org/10.15252/embr.201540509,PMC4552492,26113364,CC BY,"The family Potyviridae encompasses ∼30% of plant viruses and is responsible for significant economic losses worldwide. Recently, a small overlapping coding sequence, termed pipo, was found to be conserved in the genomes of all potyvirids. PIPO is expressed as part of a frameshift protein, P3N-PIPO, which is essential for virus cell-to-cell movement. However, the frameshift expression mechanism has hitherto remained unknown. Here, we demonstrate that transcriptional slippage, specific to the viral RNA polymerase, results in a population of transcripts with an additional “A” inserted within a highly conserved GAAAAAA sequence, thus enabling expression of P3N-PIPO. The slippage efficiency is ∼2% in Turnip mosaic virus and slippage is inhibited by mutations in the GAAAAAA sequence. While utilization of transcriptional slippage is well known in negative-sense RNA viruses such as Ebola, mumps and measles, to our knowledge this is the first report of its widespread utilization for gene expression in positive-sense RNA viruses.",2015 Aug 25,"['Olspert, Allan', 'Chung, Betty Y-W', 'Atkins, John F', 'Carr, John P', 'Firth, Andrew E']",EMBO Rep,,,False
7266d5a2b588f4bd08e301590247156d59a7f227,PMC,A Rapid Method to Characterize Mouse IgG Antibodies and Isolate Native Antigen Binding IgG B Cell Hybridomas,http://dx.doi.org/10.1371/journal.pone.0136613,PMC4552657,26317987,CC BY,"B cell hybridomas are an important source of monoclonal antibodies. In this paper, we developed a high-throughput method to characterize mouse IgG antibodies using surface plasmon resonance technology. This assay rapidly determines their sub-isotypes, whether they bind native antigen and their approximate affinities for the antigen using only 50 μl of hybridoma cell culture supernatant. Moreover, we found that mouse hybridomas secreting IgG antibodies also have membrane form IgG expression without Igα. Based on this surface IgG, we used flow cytometry to isolate rare γ2a isotype switched variants from a γ2b antibody secreting hybridoma cell line. Also, we used fluorescent antigen to single cell sort antigen binding hybridoma cells from bulk mixture of fused hybridoma cells instead of the traditional multi-microwell plate screening and limiting dilution sub-cloning thus saving time and labor. The IgG monoclonal antibodies specific for the native antigen identified with these methods are suitable for in vivo therapeutic uses, but also for sandwich ELISA assays, histology, flow cytometry, immune precipitation and x-ray crystallography.",2015 Aug 28,"['Liu, Haolin', 'White, Janice', 'Crawford, Frances', 'Jin, Niyun', 'Ju, Xiangwu', 'Liu, Kangtai', 'Jiang, Chengyu', 'Marrack, Philippa', 'Zhang, Gongyi', 'Kappler, John W.']",PLoS One,,,True
92f4de5e3cd8e63cd679d4af3db2d4d44e929ecd,PMC,Serotype 1 and 8 Pneumococci Evade Sensing by Inflammasomes in Human Lung Tissue,http://dx.doi.org/10.1371/journal.pone.0137108,PMC4552725,26317436,CC BY,"Streptococcus pneumoniae is a major cause of pneumonia, sepsis and meningitis. The pore-forming toxin pneumolysin is a key virulence factor of S. pneumoniae, which can be sensed by the NLRP3 inflammasome. Among the over 90 serotypes, serotype 1 pneumococci (particularly MLST306) have emerged across the globe as a major cause of invasive disease. The cause for its particularity is, however, incompletely understood. We therefore examined pneumococcal infection in human cells and a human lung organ culture system mimicking infection of the lower respiratory tract. We demonstrate that different pneumococcal serotypes differentially activate inflammasome-dependent IL-1β production in human lung tissue and cells. Whereas serotype 2, 3, 6B, 9N pneumococci expressing fully haemolytic pneumolysins activate NLRP3 inflammasome-dependent responses, serotype 1 and 8 strains expressing non-haemolytic toxins are poor activators of IL-1β production. Accordingly, purified haemolytic pneumolysin but not serotype 1-associated non-haemolytic toxin activates strong IL-1β production in human lungs. Our data suggest that the evasion of inflammasome-dependent innate immune responses by serotype 1 pneumococci might contribute to their ability to cause invasive diseases in humans.",2015 Aug 28,"['Fatykhova, Diana', 'Rabes, Anne', 'Machnik, Christoph', 'Guruprasad, Kunchur', 'Pache, Florence', 'Berg, Johanna', 'Toennies, Mario', 'Bauer, Torsten T.', 'Schneider, Paul', 'Schimek, Maria', 'Eggeling, Stephan', 'Mitchell, Timothy J.', 'Mitchell, Andrea M.', 'Hilker, Rolf', 'Hain, Torsten', 'Suttorp, Norbert', 'Hippenstiel, Stefan', 'Hocke, Andreas C.', 'Opitz, Bastian']",PLoS One,,,True
7432dbac9b72daf18b639ba85a59b2e676b6b09c,PMC,Different Blood Cell-Derived Transcriptome Signatures in Cows Exposed to Vaccination Pre- or Postpartum,http://dx.doi.org/10.1371/journal.pone.0136927,PMC4552870,26317664,CC BY,"Periparturient cows have been found to reveal immunosuppression, frequently associated with increased susceptibility to uterine and mammary infections. To improve understanding of the causes and molecular regulatory mechanisms accounting for this phenomenon around calving, we examined the effect of an antigen challenge on gene expression modulation on cows prior to (BC) or after calving (AC) using whole transcriptome sequencing (RNAseq). The transcriptome analysis of the cows’ blood identified a substantially higher number of loci affected in BC cows (2,235) in response to vaccination compared to AC cows (208) and revealed a divergent transcriptional profile specific for each group. In BC cows, a variety of loci involved in immune defense and cellular signaling processes were transcriptionally activated, whereas protein biosynthesis and posttranslational processes were tremendously impaired in response to vaccination. Furthermore, energy metabolism in the blood cells of BC cows was shifted from oxidative phosphorylation to the glycolytic system. In AC cows, the number and variety of regulated pathways involved in immunomodulation and maintenance of immnunocompetence are considerably lower after vaccination, and upregulation of arginine degradation was suggested as an immunosuppressive mechanism. Elevated transcript levels of erythrocyte-specific genes involved in gas exchange processes were a specific transcriptional signature in AC cows pointing to hematopoiesis activation. The divergent and substantially lower magnitude of transcriptional modulation in response to vaccination in AC cows provides evidence for a suppressed immune capacity of early lactating cows on the molecular level and demonstrates that an efficient immune response of cows is related to their physiological and metabolic status.",2015 Aug 28,"['Weikard, Rosemarie', 'Demasius, Wiebke', 'Hadlich, Frieder', 'Kühn, Christa']",PLoS One,,,True
8147b5b09a09887d1b4c4871d9d49746d8c4d418,PMC,A Multiple Antigenic Peptide Mimicking Peptidoglycan Induced T Cell Responses to Protect Mice from Systemic Infection with Staphylococcus aureus,http://dx.doi.org/10.1371/journal.pone.0136888,PMC4552945,26317210,CC BY,"Due to the enormous capacity of Staphylococcus aureus to acquire antibiotic resistance, it becomes imperative to develop vaccines for decreasing the risk of its life-threatening infections. Peptidoglycan (PGN) is a conserved and major component of S. aureus cell wall. However, it has not been used as a vaccine candidate since it is a thymus-independent antigen. In this study, we synthesized a multiple antigenic peptide, named MAP27, which comprised four copies of a peptide that mimics the epitope of PGN. After immunization with MAP27 five times and boosting with heat-inactivated bacterium one time, anti-MAP27 serum bound directly to S. aureus or PGN. Immunization with MAP27 decreased the bacterial burden in organs of BALB/c mice and significantly prolonged their survival time after S. aureus lethal-challenge. The percentage of IFN-γ(+)CD3(+) T cells and IL-17(+)CD4(+) T cells in spleen, as well as the levels of IFN-γ, IL-17A/F and CCL3 in spleen and lung, significantly increased in the MAP27-immunized mice after infection. Moreover, in vitro incubation of heat-inactivated S. aureus with splenocytes isolated from MAP27-immunized mice stimulated the production of IFN-γ and IL-17A/F. Our findings demonstrated that MAP27, as a thymus-dependent antigen, is efficient at eliciting T cell-mediated responses to protect mice from S. aureus infection. This study sheds light on a possible strategy to design vaccines against S. aureus.",2015 Aug 28,"['Wang, Xiang-Yu', 'Huang, Zhao-Xia', 'Chen, Yi-Guo', 'Lu, Xiao', 'Zhu, Ping', 'Wen, Kun', 'Fu, Ning', 'Liu, Bei-Yi']",PLoS One,,,True
e4065a39d9df47f5987404da83abbf7a10fa57db,PMC,Inhibitory effects of magnolol and honokiol on human calcitonin aggregation,http://dx.doi.org/10.1038/srep13556,PMC4555095,26324190,CC BY,"Amyloid formation is associated with multiple amyloidosis diseases. Human calcitonin (hCT) is a typical amyloidogenic peptide, its aggregation is associated with medullary carcinoma of the thyroid (MTC), and also limits its clinical application. Magnolia officinalis is a traditional Chinese herbal medicine; its two major polyphenol components, magnolol (Mag) and honokiol (Hon), have displayed multiple functions. Polyphenols like flavonoids and their derivatives have been extensively studied as amyloid inhibitors. However, the anti-amyloidogenic property of a biphenyl backbone containing polyphenols such as Mag and Hon has not been reported. In this study, these two compounds were tested for their effects on hCT aggregation. We found that Mag and Hon both inhibited the amyloid formation of hCT, whereas Mag showed a stronger inhibitory effect; moreover, they both dose-dependently disassembled preformed hCT aggregates. Further immuno-dot blot and dynamic light scattering studies suggested Mag and Hon suppressed the aggregation of hCT both at the oligomerization and the fibrillation stages, while MTT-based and dye-leakage assays demonstrated that Mag and Hon effectively reduced cytotoxicity caused by hCT aggregates. Furthermore, isothermal titration calorimetry indicated Mag and Hon both interact with hCT. Together, our study suggested a potential anti-amyloidogenic property of these two compounds and their structure related derivatives.",2015 Sep 1,"['Guo, Caiao', 'Ma, Liang', 'Zhao, Yudan', 'Peng, Anlin', 'Cheng, Biao', 'Zhou, Qiaoqiao', 'Zheng, Ling', 'Huang, Kun']",Sci Rep,,,True
e62bebc2ecb5a648b06eb708f88a8024231a474d,PMC,Cullin4 Is Pro-Viral during West Nile Virus Infection of Culex Mosquitoes,http://dx.doi.org/10.1371/journal.ppat.1005143,PMC4556628,26325027,CC BY,"Although mosquitoes serve as vectors of many pathogens of public health importance, their response to viral infection is poorly understood. It also remains to be investigated whether viruses deploy some mechanism to be able to overcome this immune response. Here, we have used an RNA-Seq approach to identify differentially regulated genes in Culex quinquefasciatus cells following West Nile virus (WNV) infection, identifying 265 transcripts from various cellular pathways that were either upregulated or downregulated. Ubiquitin-proteasomal pathway genes, comprising 12% of total differentially regulated genes, were selected for further validation by real time RT-qPCR and functional analysis. It was found that treatment of infected cells with proteasomal inhibitor, MG-132, decreased WNV titers, indicating importance of this pathway during infection process. In infection models, the Culex ortholog of mammalian Cul4A/B (cullin RING ubiquitin ligase) was found to be upregulated in vitro as well as in vivo, especially in midguts of mosquitoes. Gene knockdown using dsRNA and overexpression studies indicated that Culex Cul4 acts as a pro-viral protein by degradation of CxSTAT via ubiquitin-proteasomal pathway. We also show that gene knockdown of Culex Cul4 leads to activation of the Jak-STAT pathway in mosquitoes leading to decrease viral replication in the body as well as saliva. Our results suggest a novel mechanism adopted by WNV to overcome mosquito immune response and increase viral replication.",2015 Sep 1,"['Paradkar, Prasad N.', 'Duchemin, Jean-Bernard', 'Rodriguez-Andres, Julio', 'Trinidad, Lee', 'Walker, Peter J.']",PLoS Pathog,,,True
a087143ccafb8699cca687a6548e99633a98fe21,PMC,Blocking the PI3K/AKT pathway enhances mammalian reovirus replication by repressing IFN-stimulated genes,http://dx.doi.org/10.3389/fmicb.2015.00886,PMC4557281,26388843,CC BY,"Many host cellular signaling pathways were activated and exploited by virus infection for more efficient replication. The PI3K/Akt pathway has recently attracted considerable interest due to its role in regulating virus replication. This study demonstrated for the first time that the mammalian reovirus strains Masked Palm Civet/China/2004 (MPC/04) and Bat/China/2003 (B/03) can induce transient activation of the PI3K/Akt pathway early in infection in vitro. When UV-treated, both viruses activated PI3K/Akt signaling, indicating that the virus/receptor interaction was sufficient to activate PI3K/Akt. Reovirus virions can use both clathrin- and caveolae-mediated endocytosis, but only chlorpromazine, a specific inhibitor of clathrin-mediated endocytosis, or siRNA targeting clathrin suppressed Akt phosphorylation. We also identified the upstream molecules of the PI3K pathway. Virus infection induced phosphorylation of focal adhesion kinase (FAK) but not Gab1, and blockage of FAK phosphorylation suppressed Akt phosphorylation. Blockage of PI3K/Akt activation increased virus RNA synthesis and viral yield. We also found that reovirus infection activated the IFN-stimulated response element (ISRE) in an interferon-independent manner and up-regulated IFN-stimulated genes (ISGs) via the PI3K/Akt/EMSY pathway. Suppression of PI3K/Akt activation impaired the induction of ISRE and down-regulated the expression of ISGs. Overexpression of ISG15 and Viperin inhibited virus replication, and knockdown of either enhanced virus replication. Collectively, these results demonstrate that PI3K/Akt activated by mammalian reovirus serves as a pathway for sensing and then inhibiting virus replication/infection.",2015 Sep 2,"['Tian, Jin', 'Zhang, Xiaozhan', 'Wu, Hongxia', 'Liu, Chunguo', 'Li, Zhijie', 'Hu, Xiaoliang', 'Su, Shuo', 'Wang, Lin-Fa', 'Qu, Liandong']",Front Microbiol,,,True
e26f7a365e99b48b99e89e3f3ffcef15e6285475,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
2adb9aba7e55520011c66eea76f9b2e2e60ac108,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
da40d98e7c370e331d46f01d43d2341fd522ceef,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
fe2a2777754e368c16905eafd9c601e1d1738485,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
de664fabc611f10d71ba84039bc6784bdcf118d8,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
ca453f509ed7728ef7387c766151fbe8ed846aec,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
4e2a01fa896636962bb7924ec0c0e8b41fde379e,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
2672bf33e834b4479c328051e1bbbdcd94124587,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
7ea553f62384642e5089af579984416d77073dfe,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,False
75964abb7d9b187aab3a205e851fa6c646e9f96b,PMC,Exploring the cellular basis of human disease through a large-scale mapping of deleterious genes to cell types,http://dx.doi.org/10.1186/s13073-015-0212-9,PMC4557825,26330083,CC BY,"BACKGROUND: Each cell type found within the human body performs a diverse and unique set of functions, the disruption of which can lead to disease. However, there currently exists no systematic mapping between cell types and the diseases they can cause. METHODS: In this study, we integrate protein–protein interaction data with high-quality cell-type-specific gene expression data from the FANTOM5 project to build the largest collection of cell-type-specific interactomes created to date. We develop a novel method, called gene set compactness (GSC), that contrasts the relative positions of disease-associated genes across 73 cell-type-specific interactomes to map genes associated with 196 diseases to the cell types they affect. We conduct text-mining of the PubMed database to produce an independent resource of disease-associated cell types, which we use to validate our method. RESULTS: The GSC method successfully identifies known disease–cell-type associations, as well as highlighting associations that warrant further study. This includes mast cells and multiple sclerosis, a cell population currently being targeted in a multiple sclerosis phase 2 clinical trial. Furthermore, we build a cell-type-based diseasome using the cell types identified as manifesting each disease, offering insight into diseases linked through etiology. CONCLUSIONS: The data set produced in this study represents the first large-scale mapping of diseases to the cell types in which they are manifested and will therefore be useful in the study of disease systems. Overall, we demonstrate that our approach links disease-associated genes to the phenotypes they produce, a key goal within systems medicine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0212-9) contains supplementary material, which is available to authorized users.",2015 Sep 1,"['Cornish, Alex J.', 'Filippis, Ioannis', 'David, Alessia', 'Sternberg, Michael J.E.']",Genome Med,,,True
c4b02808f112f00b4271fcd1eabdba3b7edcc1a3,PMC,"Preparedness of Hospitals in the Republic of Ireland for an Influenza Pandemic, an Infection Control Perspective",http://dx.doi.org/10.1186/s12889-015-2025-6,PMC4557843,26335570,CC BY,"BACKGROUND: When an influenza pandemic occurs most of the population is susceptible and attack rates can range as high as 40–50 %. The most important failure in pandemic planning is the lack of standards or guidelines regarding what it means to be ‘prepared’. The aim of this study was to assess the preparedness of acute hospitals in the Republic of Ireland for an influenza pandemic from an infection control perspective. METHODS: This was a cross sectional study involving a questionnaire completed by infection control nurses, time period from June – July 2013, (3 weeks) from acute public and private hospitals in the Republic of Ireland. A total of 46 out of 56 hospitals responded to the questionnaire. RESULTS: From a sample of 46 Irish hospitals, it was found that Irish hospitals are not fully prepared for an influenza pandemic despite the 2009 Influenza A (H1N1) pandemic. In 2013, thirty five per cent of Irish hospitals have participated in an emergency plan or infectious disease exercise and have plans or been involved in local planning efforts to care for patients at non-health care facilities. Sixty per cent of Irish hospitals did not compile or did not know if the hospital had compiled a “lessons learned” from any exercise that were then used to revise emergency response plans. Fifty two per cent of hospitals have sufficient airborne isolation capacity to address routine needs and have an interim emergency plan to address needs during an outbreak. Fifty one percent of hospitals have taken specific measures to stockpile or have reserve medical supplies e.g. masks, ventilators and linen. CONCLUSIONS: This is the first study carried out in the Republic of Ireland investigating the current preparedness for an influenza pandemic from an infection control perspective. Deficits exist in the provision of emergency planning committees, testing of emergency plans, airborne isolation facilities, stockpiling of personal protective equipment (PPE) and medical supplies and organisational schemes/incentives for healthcare workers to continue to work in a pandemic. While Irish standards are comparable to findings from international studies, the health care service needs to continue to enhance preparedness for an influenza pandemic and implement standard preparedness guidance for all Irish hospitals.",2015 Sep 3,"['Reidy, Mary', 'Ryan, Fiona', 'Hogan, Dervla', 'Lacey, Sean', 'Buckley, Claire']",BMC Public Health,,,True
6cad43bc914661354dc70f971c5517021eb3a823,PMC,Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections,http://dx.doi.org/10.1371/journal.pone.0136526,PMC4558027,26332375,CC BY,"BACKGROUND: Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. METHODS: A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. RESULTS: A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). CONCLUSION: The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis.",2015 Sep 2,"['Cebey-López, Miriam', 'Herberg, Jethro', 'Pardo-Seco, Jacobo', 'Gómez-Carballa, Alberto', 'Martinón-Torres, Nazareth', 'Salas, Antonio', 'Martinón-Sánchez, José María', 'Gormley, Stuart', 'Sumner, Edward', 'Fink, Colin', 'Martinón-Torres, Federico', None]",PLoS One,,,True
208f4d527c8ac85c04dd9e431babfaaa54e66428,PMC,One Health – a strategy for resilience in a changing arctic,http://dx.doi.org/10.3402/ijch.v74.27913,PMC4558275,26333722,CC BY,"The circumpolar north is uniquely vulnerable to the health impacts of climate change. While international Arctic collaboration on health has enhanced partnerships and advanced the health of inhabitants, significant challenges lie ahead. One Health is an approach that considers the connections between the environment, plant, animal and human health. Understanding this is increasingly critical in assessing the impact of global climate change on the health of Arctic inhabitants. The effects of climate change are complex and difficult to predict with certainty. Health risks include changes in the distribution of infectious disease, expansion of zoonotic diseases and vectors, changing migration patterns, impacts on food security and changes in water availability and quality, among others. A regional network of diverse stakeholder and transdisciplinary specialists from circumpolar nations and Indigenous groups can advance the understanding of complex climate-driven health risks and provide community-based strategies for early identification, prevention and adaption of health risks in human, animals and environment. We propose a regional One Health approach for assessing interactions at the Arctic human–animal–environment interface to enhance the understanding of, and response to, the complexities of climate change on the health of the Arctic inhabitants.",2015 Sep 1,"['Ruscio, Bruce A.', 'Brubaker, Michael', 'Glasser, Joshua', 'Hueston, Will', 'Hennessy, Thomas W.']",Int J Circumpolar Health,,,True
09e8d6985e74029c794e543bde68fba0d07133a4,PMC,"Middle East respiratory syndrome coronavirus: transmission, virology and therapeutic targeting to aid in outbreak control",http://dx.doi.org/10.1038/emm.2015.76,PMC4558490,26315600,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes high fever, cough, acute respiratory tract infection and multiorgan dysfunction that may eventually lead to the death of the infected individuals. MERS-CoV is thought to be transmitted to humans through dromedary camels. The occurrence of the virus was first reported in the Middle East and it subsequently spread to several parts of the world. Since 2012, about 1368 infections, including ~487 deaths, have been reported worldwide. Notably, the recent human-to-human ‘superspreading' of MERS-CoV in hospitals in South Korea has raised a major global health concern. The fatality rate in MERS-CoV infection is four times higher compared with that of the closely related severe acute respiratory syndrome coronavirus infection. Currently, no drug has been clinically approved to control MERS-CoV infection. In this study, we highlight the potential drug targets that can be used to develop anti-MERS-CoV therapeutics.",2015 Aug 28,"['Durai, Prasannavenkatesh', 'Batool, Maria', 'Shah, Masaud', 'Choi, Sangdun']",Exp Mol Med,,,True
6695b6ccee47ef931d9a91dd8986a612ec626ea2,PMC,Transmission characteristics of MERS and SARS in the healthcare setting: a comparative study,http://dx.doi.org/10.1186/s12916-015-0450-0,PMC4558759,26336062,CC BY,"BACKGROUND: The Middle East respiratory syndrome (MERS) coronavirus has caused recurrent outbreaks in the Arabian Peninsula since 2012. Although MERS has low overall human-to-human transmission potential, there is occasional amplification in the healthcare setting, a pattern reminiscent of the dynamics of the severe acute respiratory syndrome (SARS) outbreaks in 2003. Here we provide a head-to-head comparison of exposure patterns and transmission dynamics of large hospital clusters of MERS and SARS, including the most recent South Korean outbreak of MERS in 2015. METHODS: To assess the unexpected nature of the recent South Korean nosocomial outbreak of MERS and estimate the probability of future large hospital clusters, we compared exposure and transmission patterns for previously reported hospital clusters of MERS and SARS, based on individual-level data and transmission tree information. We carried out simulations of nosocomial outbreaks of MERS and SARS using branching process models rooted in transmission tree data, and inferred the probability and characteristics of large outbreaks. RESULTS: A significant fraction of MERS cases were linked to the healthcare setting, ranging from 43.5 % for the nosocomial outbreak in Jeddah, Saudi Arabia, in 2014 to 100 % for both the outbreak in Al-Hasa, Saudi Arabia, in 2013 and the outbreak in South Korea in 2015. Both MERS and SARS nosocomial outbreaks are characterized by early nosocomial super-spreading events, with the reproduction number dropping below 1 within three to five disease generations. There was a systematic difference in the exposure patterns of MERS and SARS: a majority of MERS cases occurred among patients who sought care in the same facilities as the index case, whereas there was a greater concentration of SARS cases among healthcare workers throughout the outbreak. Exposure patterns differed slightly by disease generation, however, especially for SARS. Moreover, the distributions of secondary cases per single primary case varied highly across individual hospital outbreaks (Kruskal–Wallis test; P < 0.0001), with significantly higher transmission heterogeneity in the distribution of secondary cases for MERS than SARS. Simulations indicate a 2-fold higher probability of occurrence of large outbreaks (>100 cases) for SARS than MERS (2 % versus 1 %); however, owing to higher transmission heterogeneity, the largest outbreaks of MERS are characterized by sharper incidence peaks. The probability of occurrence of MERS outbreaks larger than the South Korean cluster (n = 186) is of the order of 1 %. CONCLUSIONS: Our study suggests that the South Korean outbreak followed a similar progression to previously described hospital clusters involving coronaviruses, with early super-spreading events generating a disproportionately large number of secondary infections, and the transmission potential diminishing greatly in subsequent generations. Differences in relative exposure patterns and transmission heterogeneity of MERS and SARS could point to changes in hospital practices since 2003 or differences in transmission mechanisms of these coronaviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0450-0) contains supplementary material, which is available to authorized users.",2015 Sep 3,"['Chowell, Gerardo', 'Abdirizak, Fatima', 'Lee, Sunmi', 'Lee, Jonggul', 'Jung, Eunok', 'Nishiura, Hiroshi', 'Viboud, Cécile']",BMC Med,,,False
30b285a628c951e7c2d73848be13204f59b2fa73,PMC,Transmission characteristics of MERS and SARS in the healthcare setting: a comparative study,http://dx.doi.org/10.1186/s12916-015-0450-0,PMC4558759,26336062,CC BY,"BACKGROUND: The Middle East respiratory syndrome (MERS) coronavirus has caused recurrent outbreaks in the Arabian Peninsula since 2012. Although MERS has low overall human-to-human transmission potential, there is occasional amplification in the healthcare setting, a pattern reminiscent of the dynamics of the severe acute respiratory syndrome (SARS) outbreaks in 2003. Here we provide a head-to-head comparison of exposure patterns and transmission dynamics of large hospital clusters of MERS and SARS, including the most recent South Korean outbreak of MERS in 2015. METHODS: To assess the unexpected nature of the recent South Korean nosocomial outbreak of MERS and estimate the probability of future large hospital clusters, we compared exposure and transmission patterns for previously reported hospital clusters of MERS and SARS, based on individual-level data and transmission tree information. We carried out simulations of nosocomial outbreaks of MERS and SARS using branching process models rooted in transmission tree data, and inferred the probability and characteristics of large outbreaks. RESULTS: A significant fraction of MERS cases were linked to the healthcare setting, ranging from 43.5 % for the nosocomial outbreak in Jeddah, Saudi Arabia, in 2014 to 100 % for both the outbreak in Al-Hasa, Saudi Arabia, in 2013 and the outbreak in South Korea in 2015. Both MERS and SARS nosocomial outbreaks are characterized by early nosocomial super-spreading events, with the reproduction number dropping below 1 within three to five disease generations. There was a systematic difference in the exposure patterns of MERS and SARS: a majority of MERS cases occurred among patients who sought care in the same facilities as the index case, whereas there was a greater concentration of SARS cases among healthcare workers throughout the outbreak. Exposure patterns differed slightly by disease generation, however, especially for SARS. Moreover, the distributions of secondary cases per single primary case varied highly across individual hospital outbreaks (Kruskal–Wallis test; P < 0.0001), with significantly higher transmission heterogeneity in the distribution of secondary cases for MERS than SARS. Simulations indicate a 2-fold higher probability of occurrence of large outbreaks (>100 cases) for SARS than MERS (2 % versus 1 %); however, owing to higher transmission heterogeneity, the largest outbreaks of MERS are characterized by sharper incidence peaks. The probability of occurrence of MERS outbreaks larger than the South Korean cluster (n = 186) is of the order of 1 %. CONCLUSIONS: Our study suggests that the South Korean outbreak followed a similar progression to previously described hospital clusters involving coronaviruses, with early super-spreading events generating a disproportionately large number of secondary infections, and the transmission potential diminishing greatly in subsequent generations. Differences in relative exposure patterns and transmission heterogeneity of MERS and SARS could point to changes in hospital practices since 2003 or differences in transmission mechanisms of these coronaviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0450-0) contains supplementary material, which is available to authorized users.",2015 Sep 3,"['Chowell, Gerardo', 'Abdirizak, Fatima', 'Lee, Sunmi', 'Lee, Jonggul', 'Jung, Eunok', 'Nishiura, Hiroshi', 'Viboud, Cécile']",BMC Med,,,True
cd9086c9edba2e717fab23027e7debb9c21c23e4,PMC,Complete Genome Sequence of Porcine Deltacoronavirus Strain CH/Sichuan/S27/2012 from Mainland China,http://dx.doi.org/10.1128/genomeA.00945-15,PMC4559728,26337879,CC BY,We report the first complete genome sequence of porcine deltacoronavirus (PDCoV) strain CH/Sichuan/S27/2012 identified in feces of diarrheic piglets from mainland China in 2012. This strain has two unique in-frame deletions within the ORF1a gene and is phylogenetically between the prototype PDCoV (HKU15) and the 2014 U.S. strains.,2015 Sep 3,"['Wang, Yi-Wen', 'Yue, Hua', 'Fang, Weihuan', 'Huang, Yao-Wei']",Genome Announc,,,True
880359b9dd6158ec31280e45a077f9d59b68e22f,PMC,"Whole-genome Sequencing for Tracing the Transmission Link between Two ARD Outbreaks Caused by a Novel HAdV Serotype 7 Variant, China",http://dx.doi.org/10.1038/srep13617,PMC4559894,26338697,CC BY,"From December 2012 to February 2013, two outbreaks of acute respiratory disease caused by HAdV-7 were reported in China. We investigated possible transmission links between these two seemingly unrelated outbreaks by integration of epidemiological and whole-genome sequencing (WGS) data. WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates. Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate. Epidemiological data supported that the first outbreak was caused by introduction of the novel HAdV-7 virus by an infected recruit upon arrival at the training base. Nosocomial transmission by close contacts was the most likely source leading to onset of the second HAdV-7 outbreak, establishing the apparent transmission link between the outbreaks. Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.",2015 Sep 4,"['Qiu, Shaofu', 'Li, Peng', 'Liu, Hongbo', 'Wang, Yong', 'Liu, Nan', 'Li, Chengyi', 'Li, Shenlong', 'Li, Ming', 'Jiang, Zhengjie', 'Sun, Huandong', 'Li, Ying', 'Xie, Jing', 'Yang, Chaojie', 'Wang, Jian', 'Li, Hao', 'Yi, Shengjie', 'Wu, Zhihao', 'Jia, Leili', 'Wang, Ligui', 'Hao, Rongzhang', 'Sun, Yansong', 'Huang, Liuyu', 'Ma, Hui', 'Yuan, Zhengquan', 'Song, Hongbin']",Sci Rep,,,True
411bf0a46d2b3dcaba0c11447380a476deb6d111,PMC,"Whole-genome Sequencing for Tracing the Transmission Link between Two ARD Outbreaks Caused by a Novel HAdV Serotype 7 Variant, China",http://dx.doi.org/10.1038/srep13617,PMC4559894,26338697,CC BY,"From December 2012 to February 2013, two outbreaks of acute respiratory disease caused by HAdV-7 were reported in China. We investigated possible transmission links between these two seemingly unrelated outbreaks by integration of epidemiological and whole-genome sequencing (WGS) data. WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates. Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate. Epidemiological data supported that the first outbreak was caused by introduction of the novel HAdV-7 virus by an infected recruit upon arrival at the training base. Nosocomial transmission by close contacts was the most likely source leading to onset of the second HAdV-7 outbreak, establishing the apparent transmission link between the outbreaks. Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.",2015 Sep 4,"['Qiu, Shaofu', 'Li, Peng', 'Liu, Hongbo', 'Wang, Yong', 'Liu, Nan', 'Li, Chengyi', 'Li, Shenlong', 'Li, Ming', 'Jiang, Zhengjie', 'Sun, Huandong', 'Li, Ying', 'Xie, Jing', 'Yang, Chaojie', 'Wang, Jian', 'Li, Hao', 'Yi, Shengjie', 'Wu, Zhihao', 'Jia, Leili', 'Wang, Ligui', 'Hao, Rongzhang', 'Sun, Yansong', 'Huang, Liuyu', 'Ma, Hui', 'Yuan, Zhengquan', 'Song, Hongbin']",Sci Rep,,,False
8ca0739bd39a043e0e9e2f67f58e899497d2658e,PMC,Targeted Collection of Plasmid DNA in Large and Growing Animal Muscles 6 Weeks after DNA Vaccination with and without Electroporation,http://dx.doi.org/10.1155/2015/326825,PMC4561992,26380318,CC BY,"DNA vaccination has been developed in the last two decades in human and animal species as a promising alternative to conventional vaccination. It consists in the injection, in the muscle, for example, of plasmid DNA encoding the vaccinating polypeptide. Electroporation which forces the entrance of the plasmid DNA in cells at the injection point has been described as a powerful and promising strategy to enhance DNA vaccine efficacy. Due to the fact that the vaccine is composed of DNA, close attention on the fate of the plasmid DNA upon vaccination has to be taken into account, especially at the injection point. To perform such studies, the muscle injection point has to be precisely recovered and collected several weeks after injection. This is even more difficult for large and growing animals. A technique has been developed to localize precisely and collect efficiently the muscle injection points in growing piglets 6 weeks after DNA vaccination accompanied or not by electroporation. Electroporation did not significantly increase the level of remaining plasmids compared to nonelectroporated piglets, and, in all the cases, the levels were below the limit recommended by the FDA to research integration events of plasmid DNA into the host DNA.",2015 Aug 25,"['Dory, Daniel', 'Le Moigne, Vincent', 'Cariolet, Roland', 'Béven, Véronique', ""Keranflec'h, André"", 'Jestin, André']",J Immunol Res,,,True
f3284e9c3eef64c4badcedf21d266309a360374a,PMC,Controlled Microwave Heating Accelerates Rolling Circle Amplification,http://dx.doi.org/10.1371/journal.pone.0136532,PMC4562646,26348227,CC BY,"Rolling circle amplification (RCA) generates single-stranded DNAs or RNA, and the diverse applications of this isothermal technique range from the sensitive detection of nucleic acids to analysis of single nucleotide polymorphisms. Microwave chemistry is widely applied to increase reaction rate as well as product yield and purity. The objectives of the present research were to apply microwave heating to RCA and indicate factors that contribute to the microwave selective heating effect. The microwave reaction temperature was strictly controlled using a microwave applicator optimized for enzymatic-scale reactions. Here, we showed that microwave-assisted RCA reactions catalyzed by either of the four thermostable DNA polymerases were accelerated over 4-folds compared with conventional RCA. Furthermore, the temperatures of the individual buffer components were specifically influenced by microwave heating. We concluded that microwave heating accelerated isothermal RCA of DNA because of the differential heating mechanisms of microwaves on the temperatures of reaction components, although the overall reaction temperatures were the same.",2015 Sep 8,"['Yoshimura, Takeo', 'Suzuki, Takamasa', 'Mineki, Shigeru', 'Ohuchi, Shokichi']",PLoS One,,,True
ddf124684188ac29dba3b174f327bd0fd62155bd,PMC,"Co-Circulation of the Rare CPV-2c with Unique Gln370Arg Substitution, New CPV-2b with Unique Thr440Ala Substitution, and New CPV-2a with High Prevalence and Variation in Heilongjiang Province, Northeast China",http://dx.doi.org/10.1371/journal.pone.0137288,PMC4562665,26348721,CC BY,"To trace evolution of canine parvovirus-2 (CPV-2), a total of 201 stool samples were collected from dogs with diarrhea in Heilongjiang province of northeast China from May 2014 to April 2015. The presence of CPV-2 in the samples was determined by PCR amplification of the VP2 gene (568 bp) of CPV-2. The results revealed that 95 samples (47.26%) were positive for CPV-2, and they showed 98.8%–100% nucleotide identity and 97.6%–100% amino acid identity. Of 95 CPV-2-positive samples, types new2a (Ser297Ala), new2b (Ser297Ala), and 2c accounted for 64.21%, 21.05%, and 14.74%, respectively. The positive rate of CPV-2 and the distribution of the new2a, new2b and 2c types exhibited differences among regions, seasons, and ages. Immunized dogs accounted for 48.42% of 95 CPV-2-positive samples. Coinfections with canine coronavirus, canine kobuvirus, and canine bocavirus were identified. Phylogenetic analysis revealed that the identified new2a, new2b, and CPV-2c strains in our study exhibited a close relationship with most of the CPV-2 strains from China; type new2a strains exhibited high variability, forming three subgroups; type new2b and CPV-2c strains formed one group with reference strains from China. Of 95 CPV-2 strains, Tyr324Ile and Thr440Ala substitutions accounted for 100% and 64.21%, respectively; all type new2b strains exhibited the Thr440Ala substitution, while the unique Gln370Arg substitution was found in all type 2c strains. Recombination analysis using entire VP2 gene indicated possible recombination events between the identified CPV-2 strains and reference strains from China. Our data revealed the co-circulation of new CPV-2a, new CPV-2b, and rare CPV-2c, as well as potential recombination events among Chinese CPV-2 strains.",2015 Sep 8,"['Geng, Yufei', 'Guo, Donghua', 'Li, Chunqiu', 'Wang, Enyu', 'Wei, Shan', 'Wang, Zhihui', 'Yao, Shuang', 'Zhao, Xiwen', 'Su, Mingjun', 'Wang, Xinyu', 'Wang, Jianfa', 'Wu, Rui', 'Feng, Li', 'Sun, Dongbo']",PLoS One,,,True
5c6b707c8cbd087e87e1a1c1f2e809cffc96a9dc,PMC,Evolutionary History of the Photolyase/Cryptochrome Superfamily in Eukaryotes,http://dx.doi.org/10.1371/journal.pone.0135940,PMC4564169,26352435,CC BY,"BACKGROUND: Photolyases and cryptochromes are evolutionarily related flavoproteins, which however perform distinct physiological functions. Photolyases (PHR) are evolutionarily ancient enzymes. They are activated by light and repair DNA damage caused by UV radiation. Although cryptochromes share structural similarity with DNA photolyases, they lack DNA repair activity. Cryptochrome (CRY) is one of the key elements of the circadian system in animals. In plants, CRY acts as a blue light receptor to entrain circadian rhythms, and mediates a variety of light responses, such as the regulation of flowering and seedling growth. RESULTS: We performed a comprehensive evolutionary analysis of the CRY/PHR superfamily. The superfamily consists of 7 major subfamilies: CPD class I and CPD class II photolyases, (6–4) photolyases, CRY-DASH, plant PHR2, plant CRY and animal CRY. Although the whole superfamily evolved primarily under strong purifying selection (average ω = 0.0168), some subfamilies did experience strong episodic positive selection during their evolution. Photolyases were lost in higher animals that suggests natural selection apparently became weaker in the late stage of evolutionary history. The evolutionary time estimates suggested that plant and animal CRYs evolved in the Neoproterozoic Era (~1000–541 Mya), which might be a result of adaptation to the major climate and global light regime changes occurred in that period of the Earth’s geological history.",2015 Sep 9,"['Mei, Qiming', 'Dvornyk, Volodymyr']",PLoS One,,,True
84b4f6a6bca69d4387ae4f6c276ce370a9def7c9,PMC,Bayesian mixture analysis for metagenomic community profiling,http://dx.doi.org/10.1093/bioinformatics/btv317,PMC4565032,26002885,CC BY,"Motivation: Deep sequencing of clinical samples is now an established tool for the detection of infectious pathogens, with direct medical applications. The large amount of data generated produces an opportunity to detect species even at very low levels, provided that computational tools can effectively profile the relevant metagenomic communities. Data interpretation is complicated by the fact that short sequencing reads can match multiple organisms and by the lack of completeness of existing databases, in particular for viral pathogens. Here we present metaMix, a Bayesian mixture model framework for resolving complex metagenomic mixtures. We show that the use of parallel Monte Carlo Markov chains for the exploration of the species space enables the identification of the set of species most likely to contribute to the mixture. Results: We demonstrate the greater accuracy of metaMix compared with relevant methods, particularly for profiling complex communities consisting of several related species. We designed metaMix specifically for the analysis of deep transcriptome sequencing datasets, with a focus on viral pathogen detection; however, the principles are generally applicable to all types of metagenomic mixtures. Availability and implementation: metaMix is implemented as a user friendly R package, freely available on CRAN: http://cran.r-project.org/web/packages/metaMix Contact: sofia.morfopoulou.10@ucl.ac.uk Supplementary information: Supplementary data are available at Bionformatics online.",2015 Sep 15,"['Morfopoulou, Sofia', 'Plagnol, Vincent']",Bioinformatics,,,True
2c96f822b3f2e493aedeaa1b3b0e32e0819dbd5b,PMC,Bayesian mixture analysis for metagenomic community profiling,http://dx.doi.org/10.1093/bioinformatics/btv317,PMC4565032,26002885,CC BY,"Motivation: Deep sequencing of clinical samples is now an established tool for the detection of infectious pathogens, with direct medical applications. The large amount of data generated produces an opportunity to detect species even at very low levels, provided that computational tools can effectively profile the relevant metagenomic communities. Data interpretation is complicated by the fact that short sequencing reads can match multiple organisms and by the lack of completeness of existing databases, in particular for viral pathogens. Here we present metaMix, a Bayesian mixture model framework for resolving complex metagenomic mixtures. We show that the use of parallel Monte Carlo Markov chains for the exploration of the species space enables the identification of the set of species most likely to contribute to the mixture. Results: We demonstrate the greater accuracy of metaMix compared with relevant methods, particularly for profiling complex communities consisting of several related species. We designed metaMix specifically for the analysis of deep transcriptome sequencing datasets, with a focus on viral pathogen detection; however, the principles are generally applicable to all types of metagenomic mixtures. Availability and implementation: metaMix is implemented as a user friendly R package, freely available on CRAN: http://cran.r-project.org/web/packages/metaMix Contact: sofia.morfopoulou.10@ucl.ac.uk Supplementary information: Supplementary data are available at Bionformatics online.",2015 Sep 15,"['Morfopoulou, Sofia', 'Plagnol, Vincent']",Bioinformatics,,,False
154eae1741c2ed718dec40b25f60eca4b56e0a74,PMC,Fiat Luc: Bioluminescence Imaging Reveals In Vivo Viral Replication Dynamics,http://dx.doi.org/10.1371/journal.ppat.1005081,PMC4565549,26356297,CC BY,,2015 Sep 10,"Mehle, Andrew",PLoS Pathog,,,True
1e8ec294fcc4507fcc89872f84adcf4633bb10e6,PMC,Evaluation of Commercial Diagnostic Assays for the Specific Detection of Avian Influenza A (H7N9) Virus RNA Using a Quality-Control Panel and Clinical Specimens in China,http://dx.doi.org/10.1371/journal.pone.0137862,PMC4567293,26361351,CC BY,"A novel avian influenza A H7N9-subtype virus emerged in China in 2013 and threatened global public health. Commercial kits that specifically detect avian influenza A (H7N9) virus RNA are urgently required to prepare for the emergence and potential pandemic of this novel influenza virus. The safety and effectiveness of three commercial molecular diagnostic assays were evaluated using a quality-control panel and clinical specimens collected from over 90 patients with confirmed avian influenza A (H7N9) virus infections. The analytical performance evaluation showed that diverse influenza H7N9 viruses can be detected with high within- and between-lot reproducibility and without cross-reactivity to other influenza viruses (H1N1 pdm09, seasonal H1N1, H3N2, H5N1 and influenza B). The detection limit of all the commercial assays was 2.83 Log(10) copies/μl [0.7 Log(10)TCID(50)/mL of avian influenza A (H7N9) virus strain A/Zhejiang/DTID-ZJU01/2013], which is comparable to the method recommended by the World Health Organization (WHO). In addition, using a WHO-Chinese National Influenza Center (CNIC) method as a reference for clinical evaluation, positive agreement of more than 98% was determined for all of the commercial kits, while negative agreement of more than 99% was observed. In conclusion, our findings provide comprehensive evidence for the high performance of three commercial diagnostic assays and suggest the application of these assays as rapid and effective diagnostic tools for avian influenza A (H7N9) virus in the routine clinical practice of medical laboratories.",2015 Sep 11,"['Shi, Dawei', 'Shen, Shu', 'Fan, Xingliang', 'Chen, Suhong', 'Wang, Dayan', 'Li, Changgui', 'Wu, Xing', 'Li, Lili', 'Bai, Dongting', 'Zhang, Chuntao', 'Wang, Junzhi']",PLoS One,,,True
f6df4efd2fd556e59aae0df8de281f84bf762dff,PMC,Changes in the Swine Gut Microbiota in Response to Porcine Epidemic Diarrhea Infection,http://dx.doi.org/10.1264/jsme2.ME15046,PMC4567570,26212519,CC BY,"The gastrointestinal tract of mammals is a complex ecosystem with distinct environments and comprises hundreds of different types of bacterial cells. The gut microbiota may play a critical role in the gut health of the host. We herein attempted to identify a microbiota shift that may be affected by porcine epidemic diarrhea (PED). We observed significant differences in microbiota between the control and PED virus (PEDV)-infected groups at both the phylum and genus level. Most commensal bacteria (i.e. Psychrobacter, Prevotella, and Faecalibacterium) in the healthy gastrointestinal tract were decreased due to dysbiosis induced by PEDV infection.",2015 Sep 25,"['Koh, Hyeon-Woo', 'Kim, Myun Soo', 'Lee, Jong-Soo', 'Kim, Hongik', 'Park, Soo-Je']",Microbes Environ,,,True
9f4050b9399c1b4b744d79edca2d37ed021ad362,PMC,Changes in the Swine Gut Microbiota in Response to Porcine Epidemic Diarrhea Infection,http://dx.doi.org/10.1264/jsme2.ME15046,PMC4567570,26212519,CC BY,"The gastrointestinal tract of mammals is a complex ecosystem with distinct environments and comprises hundreds of different types of bacterial cells. The gut microbiota may play a critical role in the gut health of the host. We herein attempted to identify a microbiota shift that may be affected by porcine epidemic diarrhea (PED). We observed significant differences in microbiota between the control and PED virus (PEDV)-infected groups at both the phylum and genus level. Most commensal bacteria (i.e. Psychrobacter, Prevotella, and Faecalibacterium) in the healthy gastrointestinal tract were decreased due to dysbiosis induced by PEDV infection.",2015 Sep 25,"['Koh, Hyeon-Woo', 'Kim, Myun Soo', 'Lee, Jong-Soo', 'Kim, Hongik', 'Park, Soo-Je']",Microbes Environ,,,True
1e9719d2d1a523240172b19f822f7a956c553fdf,PMC,Evaluation of applied public health emergency system at Prince Mohammed International Airport in Almedinah during Hajj season 2014: a qualitative case study,http://dx.doi.org/10.1186/s13104-015-1415-2,PMC4568065,26364051,CC BY,"BACKGROUND: During the Hajj season 2014, several public health measures were applied by the Ministry of Health at Prince Mohammed International Airport in Almedinah. However, several operational defects affected the provision of preventive health services for passengers and airport workers. This study aims to evaluate the applied public health emergency system at the airport, detect any potential gaps and to provide appropriate operational solutions. METHODS: This is a qualitative case study conducted at Prince Mohammed International Airport in Almedinah during the 2014 Hajj season, September 2014. Data were collected via semi-structured interviews, focus groups and policy document reviews. Interviews were conducted with the 14 individuals of the airport’s decision makers and relevant health practitioners. Data were recorded via taking notes during interviews and data coding was performed to produce the main themes and subthemes of the study. RESULTS: The main findings of the study revealed three main defects affecting the applied public health emergency system at the airport. The main themes were mainly related to shortage in logistics related to public health emergency systems, shortage in proper documentation of policies and lack of documented protocols of communications among airport stakeholders. CONCLUSIONS: The study highlighted the main factors hindering the application of public health emergency measures at the airport. A Public Health Emergency Contingency Plan was proposed as a method to regulate the process of providing logistics for public health preventive services, the method of producing documented policies and methods of producing Memoranda of Understandings as communication regulators.",2015 Sep 12,"['Gosadi, Ibrahim M.', 'BinSaeed, Abdulaziz', 'Al-Hazmi, Ali M.', 'Fadl, Amin A.', 'Alharbi, Khalid H.', 'Swarelzahab, Mazin M.']",BMC Res Notes,,,True
dd9f6d51d902c4493f797715278469d4c19bf65d,PMC,The NLRP3 Inflammasome and IL-1β Accelerate Immunologically Mediated Pathology in Experimental Viral Fulminant Hepatitis,http://dx.doi.org/10.1371/journal.ppat.1005155,PMC4569300,26367131,CC0,"Viral fulminant hepatitis (FH) is a severe disease with high mortality resulting from excessive inflammation in the infected liver. Clinical interventions have been inefficient due to the lack of knowledge for inflammatory pathogenesis in the virus-infected liver. We show that wild-type mice infected with murine hepatitis virus strain-3 (MHV-3), a model for viral FH, manifest with severe disease and high mortality in association with a significant elevation in IL-1β expression in the serum and liver. Whereas, the viral infection in IL-1β receptor-I deficient (IL-1R1 (-/-)) or IL-1R antagonist (IL-1Ra) treated mice, show reductions in virus replication, disease progress and mortality. IL-1R1 deficiency appears to debilitate the virus-induced fibrinogen-like protein-2 (FGL2) production in macrophages and CD45(+)Gr-1(high) neutrophil infiltration in the liver. The quick release of reactive oxygen species (ROS) by the infected macrophages suggests a plausible viral initiation of NLRP3 inflammasome activation. Further experiments show that mice deficient of p47 (phox), a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit that controls acute ROS production, present with reductions in NLRP3 inflammasome activation and subsequent IL-1β secretion during viral infection, which appears to be responsible for acquiring resilience to viral FH. Moreover, viral infected animals in deficiencies of NLRP3 and Caspase-1, two essential components of the inflammasome complex, also have reduced IL-1β induction along with ameliorated hepatitis. Our results demonstrate that the ROS/NLRP3/IL-1β axis institutes an essential signaling pathway, which is over activated and directly causes the severe liver disease during viral infection, which sheds light on development of efficient treatments for human viral FH and other severe inflammatory diseases.",2015 Sep 14,"['Guo, Sheng', 'Yang, Chengying', 'Diao, Bo', 'Huang, Xiaoyong', 'Jin, Meihua', 'Chen, Lili', 'Yan, Weiming', 'Ning, Qin', 'Zheng, Lixin', 'Wu, Yuzhang', 'Chen, Yongwen']",PLoS Pathog,,,True
0b0208d63d06379d846edf649d47041fc2c1aa86,PMC,Live Poultry Exposure and Public Response to Influenza A(H7N9) in Urban and Rural China during Two Epidemic Waves in 2013-2014,http://dx.doi.org/10.1371/journal.pone.0137831,PMC4569561,26367002,CC BY,"BACKGROUND: The novel influenza A(H7N9) virus has caused 2013 spring and 2013–2014 winter waves of human infections since its first emergence in China in March 2013. Exposure to live poultry is a risk factor for H7N9 infection. Public psychobehavioral responses often change during progression of an epidemic. METHODS: We conducted population-based surveys in southern China to examine human exposure to live poultry, and population psychological response and behavioral changes in the two waves. In Guangzhou, an urban area of Guangdong province, we collected data using telephone surveys with random digit dialing in May-June 2013 and again in December 2013 to January 2014. In Zijin county, a rural area of the same province, we used door-to-door surveys under a stratified sampling design in July 2013 and again in December 2013 to January 2014. All responses were weighted by age and sex to the respective adult populations. FINDINGS: Around half of the urban respondents (53.8%) reported having visited LPMs in the previous year in the first survey, around double that reported in the second survey (27.7%). In the rural surveys, around half of the participants reported raising backyard poultry in the past year in the first survey, increasing to 83.2% participants in the second survey. One third of urban subjects supported the permanent closure of LPMs in the first and second surveys, and factors associated with support for closure included female sex, higher level of worry towards H7N9, and worry induced by a hypothetical influenza-like illness. CONCLUSIONS: Our study indicated high human exposure to live poultry and low support for permanent closure of markets in both urban and rural residents regardless of increased worry during the epidemic.",2015 Sep 14,"['Wu, Peng', 'Wang, Liping', 'Cowling, Benjamin J.', 'Yu, Jianxing', 'Fang, Vicky J.', 'Li, Fu', 'Zeng, Lingjia', 'Wu, Joseph T.', 'Li, Zhongjie', 'Leung, Gabriel M.', 'Yu, Hongjie']",PLoS One,,,True
9405b40aa26445cd02d7382bf256641ca774de46,PMC,Cholesteryl Pullulan Encapsulated TNF-α Nanoparticles Are an Effective Mucosal Vaccine Adjuvant against Influenza Virus,http://dx.doi.org/10.1155/2015/471468,PMC4569761,26421290,CC BY,"We encapsulated tumor necrosis factor-α (TNF-α), a major proinflammatory cytokine, into cholesteryl pullulan (CHP) to prepare TNF/CHP nanoparticles. In this report, we describe the immune-enhancing capability of the nanoparticles to act as a vaccine adjuvant. TNF/CHP nanoparticles showed excellent storage stability and enhanced host immune responses to external immunogens. The nanoparticles were effective via the nasal route of administration for inducing systemic IgG(1) as well as mucosal IgA. We applied the nanoparticles in a model experimental influenza virus infection to investigate their adjuvant ability. TNF/CHP nanoparticles combined with a conventional split vaccine protected mice via nasal administration against a lethal challenge of A/PR/8/34 (H1N1) influenza virus. Mechanistic studies showed that the nanoparticles enhanced antigen uptake by dendritic cells (DCs) and moderately induced the expression of inflammation-related genes in nasopharynx lymphoid tissue (NALT), leading to the activation of both B and T cells. Preliminary safety study revealed no severe toxicity to TNF/CHP nanoparticles. Slight-to-moderate influences in nasal mucosa were observed only in the repeated administration and they seemed to be reversible. Our data show that TNF/CHP nanoparticles effectively enhance both humoral and cellular immunity and could be a potential adjuvant for vaccines against infectious diseases, especially in the mucosa.",2015 Sep 1,"['Nagatomo, Daiki', 'Taniai, Madoka', 'Ariyasu, Harumi', 'Taniguchi, Mutsuko', 'Aga, Miho', 'Ariyasu, Toshio', 'Ohta, Tsunetaka', 'Fukuda, Shigeharu']",Biomed Res Int,,,True
9a8d3c6485a6edc2e872b4aa7740a8e6d7ef9013,PMC,β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study,http://dx.doi.org/10.1186/s12881-015-0229-3,PMC4570703,26369942,CC BY,"BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.",2015 Sep 14,"['Wu, Pingsheng', 'Larkin, Emma K', 'Reiss, Sara S', 'Carroll, Kecia N', 'Summar, Marshall L', 'Minton, Patricia A', 'Woodward, Kimberly B', 'Liu, Zhouwen', 'Islam, Jessica Y', 'Hartert, Tina V', 'Moore, Paul E']",BMC Med Genet,,,False
d98a0e4da1857f0674df04073b816011e9c9938b,PMC,β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study,http://dx.doi.org/10.1186/s12881-015-0229-3,PMC4570703,26369942,CC BY,"BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.",2015 Sep 14,"['Wu, Pingsheng', 'Larkin, Emma K', 'Reiss, Sara S', 'Carroll, Kecia N', 'Summar, Marshall L', 'Minton, Patricia A', 'Woodward, Kimberly B', 'Liu, Zhouwen', 'Islam, Jessica Y', 'Hartert, Tina V', 'Moore, Paul E']",BMC Med Genet,,,False
e95a5be4b7bed3cc738acdf1e82e2b665c9c8cc4,PMC,β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study,http://dx.doi.org/10.1186/s12881-015-0229-3,PMC4570703,26369942,CC BY,"BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.",2015 Sep 14,"['Wu, Pingsheng', 'Larkin, Emma K', 'Reiss, Sara S', 'Carroll, Kecia N', 'Summar, Marshall L', 'Minton, Patricia A', 'Woodward, Kimberly B', 'Liu, Zhouwen', 'Islam, Jessica Y', 'Hartert, Tina V', 'Moore, Paul E']",BMC Med Genet,,,False
80e20f7b1fae3d4b8d7596cecd652ea4199549ec,PMC,β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study,http://dx.doi.org/10.1186/s12881-015-0229-3,PMC4570703,26369942,CC BY,"BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.",2015 Sep 14,"['Wu, Pingsheng', 'Larkin, Emma K', 'Reiss, Sara S', 'Carroll, Kecia N', 'Summar, Marshall L', 'Minton, Patricia A', 'Woodward, Kimberly B', 'Liu, Zhouwen', 'Islam, Jessica Y', 'Hartert, Tina V', 'Moore, Paul E']",BMC Med Genet,,,False
e67f8a93050b2405a8d6035a34d26644443d41d3,PMC,β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study,http://dx.doi.org/10.1186/s12881-015-0229-3,PMC4570703,26369942,CC BY,"BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.",2015 Sep 14,"['Wu, Pingsheng', 'Larkin, Emma K', 'Reiss, Sara S', 'Carroll, Kecia N', 'Summar, Marshall L', 'Minton, Patricia A', 'Woodward, Kimberly B', 'Liu, Zhouwen', 'Islam, Jessica Y', 'Hartert, Tina V', 'Moore, Paul E']",BMC Med Genet,,,False
fab662f7ae1f1e7ee94023c90461dba3092f915c,PMC,β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study,http://dx.doi.org/10.1186/s12881-015-0229-3,PMC4570703,26369942,CC BY,"BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.",2015 Sep 14,"['Wu, Pingsheng', 'Larkin, Emma K', 'Reiss, Sara S', 'Carroll, Kecia N', 'Summar, Marshall L', 'Minton, Patricia A', 'Woodward, Kimberly B', 'Liu, Zhouwen', 'Islam, Jessica Y', 'Hartert, Tina V', 'Moore, Paul E']",BMC Med Genet,,,False
132e94687b6ac1d68f3a33dcf090bc6f5865bb98,PMC,β(2)-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study,http://dx.doi.org/10.1186/s12881-015-0229-3,PMC4570703,26369942,CC BY,"BACKGROUND: Despite the significant interest in β(2)-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users.",2015 Sep 14,"['Wu, Pingsheng', 'Larkin, Emma K', 'Reiss, Sara S', 'Carroll, Kecia N', 'Summar, Marshall L', 'Minton, Patricia A', 'Woodward, Kimberly B', 'Liu, Zhouwen', 'Islam, Jessica Y', 'Hartert, Tina V', 'Moore, Paul E']",BMC Med Genet,,,True
80229bc73fc274591a2f0c6472a0d8c6fb966dd0,PMC,ADAP2 Is an Interferon Stimulated Gene That Restricts RNA Virus Entry,http://dx.doi.org/10.1371/journal.ppat.1005150,PMC4570769,26372645,CC BY,"Interferon stimulated genes (ISGs) target viruses at various stages of their infectious life cycles, including at the earliest stage of viral entry. Here we identify ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2) as a gene upregulated by type I IFN treatment in a STAT1-dependent manner. ADAP2 functions as a GTPase-activating protein (GAP) for Arf6 and binds to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P(3)) and PI(3,4)P(2). We show that overexpression of ADAP2 suppresses dengue virus (DENV) and vesicular stomatitis virus (VSV) infection in an Arf6 GAP activity-dependent manner, while exerting no effect on coxsackievirus B (CVB) or Sendai virus (SeV) replication. We further show that ADAP2 expression induces macropinocytosis and that ADAP2 strongly associates with actin-enriched membrane ruffles and with Rab8a- and LAMP1-, but not EEA1- or Rab7-, positive vesicles. Utilizing two techniques—light-sensitive neutral red (NR)-containing DENV and fluorescence assays for virus internalization—we show that ADAP2 primarily restricts DENV infection at the stage of virion entry and/or intracellular trafficking and that incoming DENV and VSV particles associate with ADAP2 during their entry. Taken together, this study identifies ADAP2 as an ISG that exerts antiviral effects against RNA viruses by altering Arf6-mediated trafficking to disrupt viral entry.",2015 Sep 15,"['Shu, Qian', 'Lennemann, Nicholas J.', 'Sarkar, Saumendra N.', 'Sadovsky, Yoel', 'Coyne, Carolyn B.']",PLoS Pathog,,,True
624840869f8c5f365a639a67cae53f56c740749f,PMC,Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example,http://dx.doi.org/10.1371/journal.pone.0137959,PMC4570805,26372219,CC BY,"Emerging and re-emerging infections such as SARS (2003) and pandemic H1N1 (2009) have caused concern for public health researchers and policy makers due to the increased burden of these diseases on health care systems. This concern has prompted the use of mathematical models to evaluate strategies to control disease spread, making these models invaluable tools to identify optimal intervention strategies. A particularly important quantity in infectious disease epidemiology is the basic reproduction number, R(0.) Estimation of this quantity is crucial for effective control responses in the early phase of an epidemic. In our previous study, an approach for estimating the basic reproduction number in real time was developed. This approach uses case notification data and the structure of potential transmission contacts to accurately estimate R(0) from the limited amount of information available at the early stage of an outbreak. Based on this approach, we extend the existing methodology; the most recent method features intra- and inter-age groups contact heterogeneity. Given the number of newly reported cases at the early stage of the outbreak, with parsimony assumptions on removal distribution and infectivity profile of the diseases, experiments to estimate real time R(0) under different levels of intra- and inter-group contact heterogeneity using two age groups are presented. We show that the new method converges more quickly to the actual value of R(0) than the previous one, in particular when there is high-level intra-group and inter-group contact heterogeneity. With the age specific contact patterns, number of newly reported cases, removal distribution, and information about the natural history of the 2009 pandemic influenza in Hong Kong, we also use the extended model to estimate R(0) and age-specific R(0).",2015 Sep 15,"['Kwok, Kin On', 'Davoudi, Bahman', 'Riley, Steven', 'Pourbohloul, Babak']",PLoS One,,,True
75622daf6a8bde4809687a432c5bd991d8a849ea,PMC,Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody,http://dx.doi.org/10.1038/ncomms9223,PMC4571279,26370782,CC BY,"The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (∼36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.",2015 Sep 15,"['Ying, Tianlei', 'Prabakaran, Ponraj', 'Du, Lanying', 'Shi, Wei', 'Feng, Yang', 'Wang, Yanping', 'Wang, Lingshu', 'Li, Wei', 'Jiang, Shibo', 'Dimitrov, Dimiter S.', 'Zhou, Tongqing']",Nat Commun,,,True
bf0a836e3d8d863356950aa4a760e449e5129792,PMC,Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody,http://dx.doi.org/10.1038/ncomms9223,PMC4571279,26370782,CC BY,"The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (∼36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.",2015 Sep 15,"['Ying, Tianlei', 'Prabakaran, Ponraj', 'Du, Lanying', 'Shi, Wei', 'Feng, Yang', 'Wang, Yanping', 'Wang, Lingshu', 'Li, Wei', 'Jiang, Shibo', 'Dimitrov, Dimiter S.', 'Zhou, Tongqing']",Nat Commun,,,True
f4cd52975e6aa33e8c947082eda9b261952b0f8f,PMC,Metabolic engineering of Escherichia coli into a versatile glycosylation platform: production of bio-active quercetin glycosides,http://dx.doi.org/10.1186/s12934-015-0326-1,PMC4573293,26377568,CC BY,"BACKGROUND: Flavonoids are bio-active specialized plant metabolites which mainly occur as different glycosides. Due to the increasing market demand, various biotechnological approaches have been developed which use Escherichia coli as a microbial catalyst for the stereospecific glycosylation of flavonoids. Despite these efforts, most processes still display low production rates and titers, which render them unsuitable for large-scale applications. RESULTS: In this contribution, we expanded a previously developed in vivo glucosylation platform in E. coli W, into an efficient system for selective galactosylation and rhamnosylation. The rational of the novel metabolic engineering strategy constitutes of the introduction of an alternative sucrose metabolism in the form of a sucrose phosphorylase, which cleaves sucrose into fructose and glucose 1-phosphate as precursor for UDP-glucose. To preserve these intermediates for glycosylation purposes, metabolization reactions were knocked-out. Due to the pivotal role of UDP-glucose, overexpression of the interconverting enzymes galE and MUM4 ensured the formation of both UDP-galactose and UDP-rhamnose, respectively. By additionally supplying exogenously fed quercetin and overexpressing a flavonol galactosyltransferase (F3GT) or a rhamnosyltransferase (RhaGT), 0.94 g/L hyperoside (quercetin 3-O-galactoside) and 1.12 g/L quercitrin (quercetin 3-O-rhamnoside) could be produced, respectively. In addition, both strains showed activity towards other promising dietary flavonols like kaempferol, fisetin, morin and myricetin. CONCLUSIONS: Two E. coli W mutants were engineered that could effectively produce the bio-active flavonol glycosides hyperoside and quercitrin starting from the cheap substrates sucrose and quercetin. This novel fermentation-based glycosylation strategy will allow the economically viable production of various glycosides. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12934-015-0326-1) contains supplementary material, which is available to authorized users.",2015 Sep 16,"['De Bruyn, Frederik', 'Van Brempt, Maarten', 'Maertens, Jo', 'Van Bellegem, Wouter', 'Duchi, Dries', 'De Mey, Marjan']",Microb Cell Fact,,,True
427c25eb5418afb2f27b6f27b6c7c07b4ea7af08,PMC,Lactic acid bacteria: reviewing the potential of a promising delivery live vector for biomedical purposes,http://dx.doi.org/10.1186/s12934-015-0313-6,PMC4573465,26377321,CC BY,"Lactic acid bacteria (LAB) have a long history of safe exploitation by humans, being used for centuries in food production and preservation and as probiotic agents to promote human health. Interestingly, some species of these Gram-positive bacteria, which are generally recognized as safe organisms by the US Food and Drug Administration (FDA), are able to survive through the gastrointestinal tract (GIT), being capable to reach and colonize the intestine, where they play an important role. Besides, during the last decades, an important effort has been done for the development of tools to use LAB as microbial cell factories for the production of proteins of interest. Given the need to develop effective strategies for the delivery of prophylactic and therapeutic molecules, LAB have appeared as an appealing option for the oral, intranasal and vaginal delivery of such molecules. So far, these genetically modified organisms have been successfully used as vehicles for delivering functional proteins to mucosal tissues in the treatment of many different pathologies including GIT related pathologies, diabetes, cancer and viral infections, among others. Interestingly, the administration of such microorganisms would suppose a significant decrease in the production cost of the treatments agents since being live organisms, such vectors would be able to autonomously amplify and produce and deliver the protein of interest. In this context, this review aims to provide an overview of the use of LAB engineered as a promising alternative as well as a safety delivery platform of recombinant proteins for the treatment of a wide range of diseases.",2015 Sep 16,"['Cano-Garrido, Olivia', 'Seras-Franzoso, Joaquin', 'Garcia-Fruitós, Elena']",Microb Cell Fact,,,True
e658837e4d77ef0bccdd849648e2db595f5ec65b,PMC,Survey of Ixodes pacificus Ticks in California Reveals a Diversity of Microorganisms and a Novel and Widespread Anaplasmataceae Species,http://dx.doi.org/10.1371/journal.pone.0135828,PMC4574436,26375033,CC BY,"Ixodes pacificus ticks can harbor a wide range of human and animal pathogens. To survey the prevalence of tick-borne known and putative pathogens, we tested 982 individual adult and nymphal I. pacificus ticks collected throughout California between 2007 and 2009 using a broad-range PCR and electrospray ionization mass spectrometry (PCR/ESI-MS) assay designed to detect a wide range of tick-borne microorganisms. Overall, 1.4% of the ticks were found to be infected with Borrelia burgdorferi, 2.0% were infected with Borrelia miyamotoi and 0.3% were infected with Anaplasma phagocytophilum. In addition, 3.0% were infected with Babesia odocoilei. About 1.2% of the ticks were co-infected with more than one pathogen or putative pathogen. In addition, we identified a novel Anaplasmataceae species that we characterized by sequencing of its 16S rRNA, groEL, gltA, and rpoB genes. Sequence analysis indicated that this organism is phylogenetically distinct from known Anaplasma species with its closest genetic near neighbors coming from Asia. The prevalence of this novel Anaplasmataceae species was as high as 21% at one site, and it was detected in 4.9% of ticks tested statewide. Based upon this genetic characterization we propose that this organism be called ‘Candidatus Cryptoplasma californiense’. Knowledge of this novel microbe will provide awareness for the community about the breadth of the I. pacificus microbiome, the concept that this bacterium could be more widely spread; and an opportunity to explore whether this bacterium also contributes to human or animal disease burden.",2015 Sep 16,"['Eshoo, Mark W.', 'Carolan, Heather E.', 'Massire, Christian', 'Chou, Danny M.', 'Crowder, Chris D.', 'Rounds, Megan A.', 'Phillipson, Curtis A.', 'Schutzer, Steven E.', 'Ecker, David J.']",PLoS One,,,True
6548b941beede8bb57cde83a928e4383b54697ad,PMC,"Povidone-iodine hand wash and hand rub products demonstrated excellent in vitro virucidal efficacy against Ebola virus and modified vaccinia virus Ankara, the new European test virus for enveloped viruses",http://dx.doi.org/10.1186/s12879-015-1111-9,PMC4574578,26381737,CC BY,"BACKGROUND: The recent Ebola virus (EBOV) epidemic highlights the need for efficacious virucidal products to help prevent infection and limit the spread of Ebola virus disease. However, there is limited data on the efficacy of virucidal products against EBOV, because the virus has a high biosafety level and is only available in a few laboratories worldwide. The virucidal efficacy of antiseptics and disinfectants can be determined using the European Standard EN14476:2013/FprA1:2015. Modified vaccinia virus Ankara (MVA) was introduced in 2014 as a reference virus for the claim ‘virucidal active against enveloped viruses for hygienic hand rub and hand wash’. For EBOV, also an enveloped virus, the suitability of MVA as a surrogate needs to be proven. The aim of this study was to test the in vitro efficacy of four povidone iodine (PVP-I) formulations against EBOV: 4 % PVP-I skin cleanser; 7.5 % PVP-I surgical scrub; 10 % PVP-I solution; and 3.2 % PVP-I and 78 % alcohol solution. The formulations were tested with MVA to define the test conditions, and as a secondary objective the suitability of MVA as a surrogate for enveloped viruses like EBOV was assessed. METHODS: According to EN14476, a standard suspension test was used for MVA. Large-volume plating was used for EBOV to increase test sensitivity and exclude potential after-effects. All products were tested under clean (0.3 g/L BSA) and dirty (3.0 g/L BSA + 3.0 mL/L erythrocytes) conditions with MVA for 15, 30, and 60 s. The concentration-contact time values obtained with MVA were verified for EBOV. RESULTS: Viral titres of MVA and EBOV were reduced by >99.99 % to >99.999 % under clean and dirty conditions after application of the test products for 15 seconds. CONCLUSIONS: All products showed excellent virucidal efficacy against EBOV, demonstrating the important role PVP-I can play in helping to prevent and limit the spread of Ebola virus disease. The efficacy against both test viruses after 15 s is helpful information for the implementation of guidance for people potentially exposed to EBOV, and confirms the excellent virucidal efficacy of PVP-I against enveloped viruses. MVA was found to be a suitable surrogate for enveloped viruses like EBOV.",2015 Sep 17,"['Eggers, Maren', 'Eickmann, Markus', 'Kowalski, Katharina', 'Zorn, Juergen', 'Reimer, Karen']",BMC Infect Dis,,,True
8f962ad62ba3d5af7c52898283c4827ff71a5949,PMC,TMPRSS2 Isoform 1 Activates Respiratory Viruses and Is Expressed in Viral Target Cells,http://dx.doi.org/10.1371/journal.pone.0138380,PMC4574978,26379044,CC BY,"The cellular protease TMPRSS2 cleaves and activates the influenza virus hemagglutinin (HA) and TMPRSS2 expression is essential for viral spread and pathogenesis in mice. Moreover, severe acute respiratory syndrome coronavirus (SARS-CoV) and other respiratory viruses are activated by TMPRSS2. However, previous studies on viral activation by TMPRSS2 focused on a 492 amino acids comprising form of the protein (isoform 2) while other TMPRSS2 isoforms, generated upon alternative splicing of the tmprss2 mRNA, have not been characterized. Here, we show that the mRNA encoding a TMPRSS2 isoform with an extended N-terminal cytoplasmic domain (isoform 1) is expressed in lung-derived cell lines and tissues. Moreover, we demonstrate that TMPRSS2 isoform 1 colocalizes with HA and cleaves and activates HA. Finally, we show that isoform 1 activates the SARS-CoV spike protein for cathepsin L-independent entry into target cells. Our results indicate that TMPRSS2 isoform 1 is expressed in viral target cells and might contribute to viral activation in the host.",2015 Sep 17,"['Zmora, Pawel', 'Moldenhauer, Anna-Sophie', 'Hofmann-Winkler, Heike', 'Pöhlmann, Stefan']",PLoS One,,,True
9d18d8401ce2aa056ff228fce06c4a2d8c7f67f0,PMC,Transcriptome Analysis Reveals the Mechanism Underlying the Production of a High Quantity of Chlorogenic Acid in Young Leaves of Lonicera macranthoides Hand.-Mazz,http://dx.doi.org/10.1371/journal.pone.0137212,PMC4575056,26381882,CC BY,"Lonicera macranthoides Hand.-Mazz (L. macranthoides) is a medicinal herb that is widely distributed in southern China. The biosynthetic and metabolic pathways for a core secondary metabolite in L. macranthoides, chlorogenic acid (CGA), have been elucidated in many species. However, the mechanisms of CGA biosynthesis and the related gene regulatory network in L. macranthoides are still not well understood. In this study, CGA content was quantified by high performance liquid chromatography (HPLC), and CGA levels differed significantly among three tissues; specifically, the CGA content in young leaves (YL) was greater than that in young stems (YS), which was greater than that in mature flowers (MF). Transcriptome analysis of L. macranthoides yielded a total of 53,533,014 clean reads (average length 90 bp) and 76,453 unigenes (average length 703 bp). A total of 3,767 unigenes were involved in biosynthesis pathways of secondary metabolites. Of these unigenes, 80 were possibly related to CGA biosynthesis. Furthermore, differentially expressed genes (DEGs) were screened in different tissues including YL, MF and YS. In these tissues, 24 DEGs were found to be associated with CGA biosynthesis, including six phenylalanine ammonia lyase (PAL) genes, six 4-coumarate coenzyme A ligase (4CL) genes, four cinnamate 4-Hydroxylase (C4H) genes, seven hydroxycinnamoyl transferase/hydroxycinnamoyl-CoA quinate transferase HCT/HQT genes and one coumarate 3-hydroxylase (C3H) gene.These results further the understanding of CGA biosynthesis and the related regulatory network in L. macranthoides.",2015 Sep 18,"['Chen, Zexiong', 'Tang, Ning', 'You, Yuming', 'Lan, Jianbin', 'Liu, Yiqing', 'Li, Zhengguo']",PLoS One,,,True
59e339e8a09eb0b00c603cbd5867d8edabc2151d,PMC,Colorimetric Detection of Dengue by Single Tube Reverse-Transcription-Loop-Mediated Isothermal Amplification,http://dx.doi.org/10.1371/journal.pone.0138694,PMC4575147,26384248,CC BY,"Dengue is usually diagnosed by isolation of the virus, serology or molecular diagnostic methods. Several commercial kits for the diagnosis of dengue are existing, but concerns have arisen regarding to the affordability and performance characteristics of these kits. Hence, the loop-mediated isothermal amplification (LAMP) is potentially ideal to be used especially in resource limited environments. Serum was collected from healthy donors and patients diagnosed with dengue infection. RNA extracted from the serum samples were tested by reverse-transcription-LAMP assay developed based on 3′-NCR gene sequences for DENV 1–4. Results were interpreted by a turbidity meter in real time or visually at the end of the assay. Sensitivity and specificity of RT-LAMP results were calculated and compared to qRT-PCR and ELISA. RT-LAMP is highly sensitive with the detection limit of 10 RNA copies for all serotypes. Dengue virus RNA was detected in all positive samples using RT-LAMP and none of the negative samples within 30–45 minutes. With continuing efforts in the optimization of this assay, RT-LAMP may provide a simple and reliable test for detecting DENV in areas where dengue is prevalent.",2015 Sep 18,"['Lau, Yee-Ling', 'Lai, Meng-Yee', 'Teoh, Boon-Teong', 'Abd-Jamil, Juraina', 'Johari, Jefree', 'Sam, Sing-Sin', 'Tan, Kim-Kee', 'AbuBakar, Sazaly']",PLoS One,,,True
94f67a30df65c02cf339d2276e04afda40f59072,PMC,High-Throughput Ligand Discovery Reveals a Sitewise Gradient of Diversity in Broadly Evolved Hydrophilic Fibronectin Domains,http://dx.doi.org/10.1371/journal.pone.0138956,PMC4575168,26383268,CC BY,"Discovering new binding function via a combinatorial library in small protein scaffolds requires balance between appropriate mutations to introduce favorable intermolecular interactions while maintaining intramolecular integrity. Sitewise constraints exist in a non-spatial gradient from diverse to conserved in evolved antibody repertoires; yet non-antibody scaffolds generally do not implement this strategy in combinatorial libraries. Despite the fact that biased amino acid distributions, typically elevated in tyrosine, serine, and glycine, have gained wider use in synthetic scaffolds, these distributions are still predominantly applied uniformly to diversified sites. While select sites in fibronectin domains and DARPins have shown benefit from sitewise designs, they have not been deeply evaluated. Inspired by this disparity between diversity distributions in natural libraries and synthetic scaffold libraries, we hypothesized that binders resulting from discovery and evolution would exhibit a non-spatial, sitewise gradient of amino acid diversity. To identify sitewise diversities consistent with efficient evolution in the context of a hydrophilic fibronectin domain, >10(5) binders to six targets were evolved and sequenced. Evolutionarily favorable amino acid distributions at 25 sites reveal Shannon entropies (range: 0.3–3.9; median: 2.1; standard deviation: 1.1) supporting the diversity gradient hypothesis. Sitewise constraints in evolved sequences are consistent with complementarity, stability, and consensus biases. Implementation of sitewise constrained diversity enables direct selection of nanomolar affinity binders validating an efficient strategy to balance inter- and intra-molecular interaction demands at each site.",2015 Sep 18,"['Woldring, Daniel R.', 'Holec, Patrick V.', 'Zhou, Hong', 'Hackel, Benjamin J.']",PLoS One,,,True
5578dcb4f631bb4fabcf4d607327ee0bf1f133d1,PMC,High-Throughput Ligand Discovery Reveals a Sitewise Gradient of Diversity in Broadly Evolved Hydrophilic Fibronectin Domains,http://dx.doi.org/10.1371/journal.pone.0138956,PMC4575168,26383268,CC BY,"Discovering new binding function via a combinatorial library in small protein scaffolds requires balance between appropriate mutations to introduce favorable intermolecular interactions while maintaining intramolecular integrity. Sitewise constraints exist in a non-spatial gradient from diverse to conserved in evolved antibody repertoires; yet non-antibody scaffolds generally do not implement this strategy in combinatorial libraries. Despite the fact that biased amino acid distributions, typically elevated in tyrosine, serine, and glycine, have gained wider use in synthetic scaffolds, these distributions are still predominantly applied uniformly to diversified sites. While select sites in fibronectin domains and DARPins have shown benefit from sitewise designs, they have not been deeply evaluated. Inspired by this disparity between diversity distributions in natural libraries and synthetic scaffold libraries, we hypothesized that binders resulting from discovery and evolution would exhibit a non-spatial, sitewise gradient of amino acid diversity. To identify sitewise diversities consistent with efficient evolution in the context of a hydrophilic fibronectin domain, >10(5) binders to six targets were evolved and sequenced. Evolutionarily favorable amino acid distributions at 25 sites reveal Shannon entropies (range: 0.3–3.9; median: 2.1; standard deviation: 1.1) supporting the diversity gradient hypothesis. Sitewise constraints in evolved sequences are consistent with complementarity, stability, and consensus biases. Implementation of sitewise constrained diversity enables direct selection of nanomolar affinity binders validating an efficient strategy to balance inter- and intra-molecular interaction demands at each site.",2015 Sep 18,"['Woldring, Daniel R.', 'Holec, Patrick V.', 'Zhou, Hong', 'Hackel, Benjamin J.']",PLoS One,,,False
bb295c0aee03f7bed96537c61729f82ab14a3467,PMC,High-Throughput Ligand Discovery Reveals a Sitewise Gradient of Diversity in Broadly Evolved Hydrophilic Fibronectin Domains,http://dx.doi.org/10.1371/journal.pone.0138956,PMC4575168,26383268,CC BY,"Discovering new binding function via a combinatorial library in small protein scaffolds requires balance between appropriate mutations to introduce favorable intermolecular interactions while maintaining intramolecular integrity. Sitewise constraints exist in a non-spatial gradient from diverse to conserved in evolved antibody repertoires; yet non-antibody scaffolds generally do not implement this strategy in combinatorial libraries. Despite the fact that biased amino acid distributions, typically elevated in tyrosine, serine, and glycine, have gained wider use in synthetic scaffolds, these distributions are still predominantly applied uniformly to diversified sites. While select sites in fibronectin domains and DARPins have shown benefit from sitewise designs, they have not been deeply evaluated. Inspired by this disparity between diversity distributions in natural libraries and synthetic scaffold libraries, we hypothesized that binders resulting from discovery and evolution would exhibit a non-spatial, sitewise gradient of amino acid diversity. To identify sitewise diversities consistent with efficient evolution in the context of a hydrophilic fibronectin domain, >10(5) binders to six targets were evolved and sequenced. Evolutionarily favorable amino acid distributions at 25 sites reveal Shannon entropies (range: 0.3–3.9; median: 2.1; standard deviation: 1.1) supporting the diversity gradient hypothesis. Sitewise constraints in evolved sequences are consistent with complementarity, stability, and consensus biases. Implementation of sitewise constrained diversity enables direct selection of nanomolar affinity binders validating an efficient strategy to balance inter- and intra-molecular interaction demands at each site.",2015 Sep 18,"['Woldring, Daniel R.', 'Holec, Patrick V.', 'Zhou, Hong', 'Hackel, Benjamin J.']",PLoS One,,,False
68c511101e72f75c7c7146306567114789e25be4,PMC,High-Throughput Ligand Discovery Reveals a Sitewise Gradient of Diversity in Broadly Evolved Hydrophilic Fibronectin Domains,http://dx.doi.org/10.1371/journal.pone.0138956,PMC4575168,26383268,CC BY,"Discovering new binding function via a combinatorial library in small protein scaffolds requires balance between appropriate mutations to introduce favorable intermolecular interactions while maintaining intramolecular integrity. Sitewise constraints exist in a non-spatial gradient from diverse to conserved in evolved antibody repertoires; yet non-antibody scaffolds generally do not implement this strategy in combinatorial libraries. Despite the fact that biased amino acid distributions, typically elevated in tyrosine, serine, and glycine, have gained wider use in synthetic scaffolds, these distributions are still predominantly applied uniformly to diversified sites. While select sites in fibronectin domains and DARPins have shown benefit from sitewise designs, they have not been deeply evaluated. Inspired by this disparity between diversity distributions in natural libraries and synthetic scaffold libraries, we hypothesized that binders resulting from discovery and evolution would exhibit a non-spatial, sitewise gradient of amino acid diversity. To identify sitewise diversities consistent with efficient evolution in the context of a hydrophilic fibronectin domain, >10(5) binders to six targets were evolved and sequenced. Evolutionarily favorable amino acid distributions at 25 sites reveal Shannon entropies (range: 0.3–3.9; median: 2.1; standard deviation: 1.1) supporting the diversity gradient hypothesis. Sitewise constraints in evolved sequences are consistent with complementarity, stability, and consensus biases. Implementation of sitewise constrained diversity enables direct selection of nanomolar affinity binders validating an efficient strategy to balance inter- and intra-molecular interaction demands at each site.",2015 Sep 18,"['Woldring, Daniel R.', 'Holec, Patrick V.', 'Zhou, Hong', 'Hackel, Benjamin J.']",PLoS One,,,True
d06179d5a694b2d0a7e610a279739776ba33e1ae,PMC,High-Throughput Ligand Discovery Reveals a Sitewise Gradient of Diversity in Broadly Evolved Hydrophilic Fibronectin Domains,http://dx.doi.org/10.1371/journal.pone.0138956,PMC4575168,26383268,CC BY,"Discovering new binding function via a combinatorial library in small protein scaffolds requires balance between appropriate mutations to introduce favorable intermolecular interactions while maintaining intramolecular integrity. Sitewise constraints exist in a non-spatial gradient from diverse to conserved in evolved antibody repertoires; yet non-antibody scaffolds generally do not implement this strategy in combinatorial libraries. Despite the fact that biased amino acid distributions, typically elevated in tyrosine, serine, and glycine, have gained wider use in synthetic scaffolds, these distributions are still predominantly applied uniformly to diversified sites. While select sites in fibronectin domains and DARPins have shown benefit from sitewise designs, they have not been deeply evaluated. Inspired by this disparity between diversity distributions in natural libraries and synthetic scaffold libraries, we hypothesized that binders resulting from discovery and evolution would exhibit a non-spatial, sitewise gradient of amino acid diversity. To identify sitewise diversities consistent with efficient evolution in the context of a hydrophilic fibronectin domain, >10(5) binders to six targets were evolved and sequenced. Evolutionarily favorable amino acid distributions at 25 sites reveal Shannon entropies (range: 0.3–3.9; median: 2.1; standard deviation: 1.1) supporting the diversity gradient hypothesis. Sitewise constraints in evolved sequences are consistent with complementarity, stability, and consensus biases. Implementation of sitewise constrained diversity enables direct selection of nanomolar affinity binders validating an efficient strategy to balance inter- and intra-molecular interaction demands at each site.",2015 Sep 18,"['Woldring, Daniel R.', 'Holec, Patrick V.', 'Zhou, Hong', 'Hackel, Benjamin J.']",PLoS One,,,False
5bd910b6b8b82e7b70c97ebe2c34ad638236c67d,PMC,The Virus-Host Interplay: Biogenesis of +RNA Replication Complexes,http://dx.doi.org/10.3390/v7082825,PMC4576186,26287230,CC BY,"Positive-strand RNA (+RNA) viruses are an important group of human and animal pathogens that have significant global health and economic impacts. Notable members include West Nile virus, Dengue virus, Chikungunya, Severe acute respiratory syndrome (SARS) Coronavirus and enteroviruses of the Picornaviridae family.Unfortunately, prophylactic and therapeutic treatments against these pathogens are limited. +RNA viruses have limited coding capacity and thus rely extensively on host factors for successful infection and propagation. A common feature among these viruses is their ability to dramatically modify cellular membranes to serve as platforms for genome replication and assembly of new virions. These viral replication complexes (VRCs) serve two main functions: To increase replication efficiency by concentrating critical factors and to protect the viral genome from host anti-viral systems. This review summarizes current knowledge of critical host factors recruited to or demonstrated to be involved in the biogenesis and stabilization of +RNA virus VRCs.",2015 Aug 6,"['Reid, Colleen R.', 'Airo, Adriana M.', 'Hobman, Tom C.']",Viruses,,,True
1c07f420a5a01bec7481025a89f2621596a99782,PMC,Structural and Functional Properties of the Hepatitis C Virus p7 Viroporin,http://dx.doi.org/10.3390/v7082826,PMC4576187,26258788,CC BY,"The high prevalence of hepatitis C virus (HCV) infection in the human population has triggered intensive research efforts that have led to the development of curative antiviral therapy. Moreover, HCV has become a role model to study fundamental principles that govern the replication cycle of a positive strand RNA virus. In fact, for most HCV proteins high-resolution X-ray and NMR (Nuclear Magnetic Resonance)-based structures have been established and profound insights into their biochemical and biological properties have been gained. One example is p7, a small hydrophobic protein that is dispensable for RNA replication, but crucial for the production and release of infectious HCV particles from infected cells. Owing to its ability to insert into membranes and assemble into homo-oligomeric complexes that function as minimalistic ion channels, HCV p7 is a member of the viroporin family. This review compiles the most recent findings related to the structure and dual pore/ion channel activity of p7 of different HCV genotypes. The alternative conformations and topologies proposed for HCV p7 in its monomeric and oligomeric state are described and discussed in detail. We also summarize the different roles p7 might play in the HCV replication cycle and highlight both the ion channel/pore-like function and the additional roles of p7 unrelated to its channel activity. Finally, we discuss possibilities to utilize viroporin inhibitors for antagonizing p7 ion channel/pore-like activity.",2015 Aug 6,"['Madan, Vanesa', 'Bartenschlager, Ralf']",Viruses,,,True
b51c5f53980e0118362f26862e1243aac186a4ab,PMC,Genetic Characterization of the Belgian Nephropathogenic Infectious Bronchitis Virus (NIBV) Reference Strain B1648,http://dx.doi.org/10.3390/v7082827,PMC4576188,26262637,CC BY,"The virulent nephropathogenic infectious bronchitis virus (NIBV) strain B1648 was first isolated in 1984, in Flanders, Belgium. Despite intensive vaccination, B1648 and its variants are still circulating in Europe and North Africa. Here, the full-length genome of this Belgian NIBV reference strain was determined by next generation sequencing (NGS) to understand its evolutionary relationship with other IBV strains, and to identify possible genetic factors that may be associated with the nephropathogenicity. Thirteen open reading frames (ORFs) were predicted in the B1648 strain (5′UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-3′UTR). ORFs 4b, 4c and 6b, which have been rarely reported in literature, were present in B1648 and most of the other IBV complete genomes. According to phylogenetic analysis of the full-length genome, replicase transcriptase complex, spike protein, partial S1 gene and M protein, B1648 strain clustered with the non-Massachusetts type strains NGA/A116E7/2006, UKr 27-11, QX-like ITA/90254/2005, QX-like CK/SWE/0658946/10, TN20/00, RF-27/99, RF/06/2007 and SLO/266/05. Based on the partial S1 fragment, B1648 clustered with the strains TN20/00, RF-27/99, RF/06/2007 and SLO/266/05 and, further designated as B1648 genotype. The full-length genome of B1648 shared the highest sequence homology with UKr 27-11, Gray, JMK, and NGA/A116E7/2006 (91.2% to 91.6%) and was least related with the reference Beaudette and Massachusetts strains (89.7%). Nucleotide and amino acid sequence analyses indicated that B1648 strain may have played an important role in the evolution of IBV in Europe and North Africa. Further, the nephropathogenicity determinants might be located on the 1a, spike, M and accessory proteins (3a, 3b, 4b, 4c, 5a, 5b and 6b). Overall, strain B1648 is distinct from all the strains reported so far in Europe and other parts of the world.",2015 Aug 7,"['Reddy, Vishwanatha R.A.P.', 'Theuns, Sebastiaan', 'Roukaerts, Inge D.M.', 'Zeller, Mark', 'Matthijnssens, Jelle', 'Nauwynck, Hans J.']",Viruses,,,True
49335e838ecac21b1628a2aa0877f2d56562a1b7,PMC,Genetic Characterization of the Belgian Nephropathogenic Infectious Bronchitis Virus (NIBV) Reference Strain B1648,http://dx.doi.org/10.3390/v7082827,PMC4576188,26262637,CC BY,"The virulent nephropathogenic infectious bronchitis virus (NIBV) strain B1648 was first isolated in 1984, in Flanders, Belgium. Despite intensive vaccination, B1648 and its variants are still circulating in Europe and North Africa. Here, the full-length genome of this Belgian NIBV reference strain was determined by next generation sequencing (NGS) to understand its evolutionary relationship with other IBV strains, and to identify possible genetic factors that may be associated with the nephropathogenicity. Thirteen open reading frames (ORFs) were predicted in the B1648 strain (5′UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-3′UTR). ORFs 4b, 4c and 6b, which have been rarely reported in literature, were present in B1648 and most of the other IBV complete genomes. According to phylogenetic analysis of the full-length genome, replicase transcriptase complex, spike protein, partial S1 gene and M protein, B1648 strain clustered with the non-Massachusetts type strains NGA/A116E7/2006, UKr 27-11, QX-like ITA/90254/2005, QX-like CK/SWE/0658946/10, TN20/00, RF-27/99, RF/06/2007 and SLO/266/05. Based on the partial S1 fragment, B1648 clustered with the strains TN20/00, RF-27/99, RF/06/2007 and SLO/266/05 and, further designated as B1648 genotype. The full-length genome of B1648 shared the highest sequence homology with UKr 27-11, Gray, JMK, and NGA/A116E7/2006 (91.2% to 91.6%) and was least related with the reference Beaudette and Massachusetts strains (89.7%). Nucleotide and amino acid sequence analyses indicated that B1648 strain may have played an important role in the evolution of IBV in Europe and North Africa. Further, the nephropathogenicity determinants might be located on the 1a, spike, M and accessory proteins (3a, 3b, 4b, 4c, 5a, 5b and 6b). Overall, strain B1648 is distinct from all the strains reported so far in Europe and other parts of the world.",2015 Aug 7,"['Reddy, Vishwanatha R.A.P.', 'Theuns, Sebastiaan', 'Roukaerts, Inge D.M.', 'Zeller, Mark', 'Matthijnssens, Jelle', 'Nauwynck, Hans J.']",Viruses,,,False
f793bcacac81ad9341709c9351c6c40c49f4c52e,PMC,eEF1A Interacts with the NS5A Protein and Inhibits the Growth of Classical Swine Fever Virus,http://dx.doi.org/10.3390/v7082833,PMC4576194,26266418,CC BY,"The NS5A protein of classical swine fever virus (CSFV) is involved in the RNA synthesis and viral replication. However, the NS5A-interacting cellular proteins engaged in the CSFV replication are poorly defined. Using yeast two-hybrid screen, the eukaryotic elongation factor 1A (eEF1A) was identified to be an NS5A-binding partner. The NS5A–eEF1A interaction was confirmed by coimmunoprecipitation, glutathione S-transferase (GST) pulldown and laser confocal microscopy assays. The domain I of eEF1A was shown to be critical for the NS5A–eEF1A interaction. Overexpression of eEF1A suppressed the CSFV growth markedly, and conversely, knockdown of eEF1A enhanced the CSFV replication significantly. Furthermore, eEF1A, as well as NS5A, was found to reduce the translation efficiency of the internal ribosome entry site (IRES) of CSFV in a dose-dependent manner, as demonstrated by luciferase reporter assay. Streptavidin pulldown assay revealed that eEF1A could bind to the CSFV IRES. Collectively, our results suggest that eEF1A interacts with NS5A and negatively regulates the growth of CSFV.",2015 Aug 10,"['Li, Su', 'Feng, Shuo', 'Wang, Jing-Han', 'He, Wen-Rui', 'Qin, Hua-Yang', 'Dong, Hong', 'Li, Lian-Feng', 'Yu, Shao-Xiong', 'Li, Yongfeng', 'Qiu, Hua-Ji']",Viruses,,,True
fdc201b99c8f08d1e81622ac71114605c5980a8d,PMC,Vaccine Induced Herd Immunity for Control of Respiratory Syncytial Virus Disease in a Low-Income Country Setting,http://dx.doi.org/10.1371/journal.pone.0138018,PMC4577090,26390032,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is globally ubiquitous, and infection during the first six months of life is a major risk for severe disease and hospital admission; consequently RSV is the most important viral cause of respiratory morbidity and mortality in young children. Development of vaccines for young infants is complicated by the presence of maternal antibodies and immunological immaturity, but vaccines targeted at older children avoid these problems. Vaccine development for young infants has been unsuccessful, but this is not the case for older children (> 6m). Would vaccinating older children have a significant public health impact? We developed a mathematical model to explore the benefits of a vaccine against RSV. METHODS AND FINDINGS: We have used a deterministic age structured model capturing the key epidemiological characteristics of RSV and performed a statistical maximum-likelihood fit to age-specific hospitalization data from a developing country setting. To explore the effects of vaccination under different mixing assumptions, we included two versions of contact matrices: one from a social contact diary study, and the second a synthesised construction based on demographic data. Vaccination is assumed to elicit an immune response equivalent to primary infection. Our results show that immunisation of young children (5–10m) is likely to be a highly effective method of protection of infants (<6m) against hospitalisation. The majority benefit is derived from indirect protection (herd immunity). A full sensitivity and uncertainty analysis using Latin Hypercube Sampling of the parameter space shows that our results are robust to model structure and model parameters. CONCLUSIONS: This result suggests that vaccinating older infants and children against RSV can have a major public health benefit.",2015 Sep 21,"['Kinyanjui, Timothy M.', 'House, Thomas A.', 'Kiti, Moses C.', 'Cane, Patricia A.', 'Nokes, David J.', 'Medley, Graham F.']",PLoS One,,,True
3c568d47a1d134908dc09e454a5a52655d3a9434,PMC,The Acute Chest Syndrome in Cameroonian children living with sickle cell disease,http://dx.doi.org/10.1186/s12887-015-0454-0,PMC4578678,26391669,CC BY,"BACKGROUND: Although sub-Saharan Africa (SSA) is particularly affected by sickle cell disease (SCD), there is dearth of research on this topic in the region, specifically targeting the magnitude of SCD-related complications. We therefore conducted this study to determine the burden of acute chest syndrome (ACS) and describe its clinical and therapeutic aspects among SCD children in Cameroon, a SSA country. METHODS: This was a retrospective study carried-out from September 2013 to June 2014 at the SCD unit of the Mother and Child Centre of the Chantal Biya Foundation, a pediatric reference centre in Yaoundé, Cameroon. We enrolled all SCD children with confirmed diagnosis of ACS, and recorded their clinical presentation at admission along with their evolution during hospitalization. RESULTS: Twenty one cases of ACS were identified during the study period, from 338 hospitalizations of children with SCD. Ages ranged from 11 months to 16 years with a mean (standard deviation) of 5.5 (3.4) years, and a male/female sex ratio of 3.2/1. We noticed relatively low levels of HbF, from 6.4 to 21.9 % with a mean of 14.6 % (6.0 %). The three main symptoms at admission were fever (90.5 %), cough (81 %) and chest pains (28.6 %). Two patients (9.5 %) developed ACS 2 days after admission. The mean values of leukocytes, neutrophils, serum CRP, serum LDH and hemoglobin were respectively 32479.4 (17862.3)/mm(3), 23476 (11543.7)/mm(3), 228.2 (132.6) mg/l, 3452.3 (2916.3) IU/l and 6.5 (1.2) g/dl. The main localizations of radiological alveolar consolidations were the lower lobes (90.5 %). Treatment associated broad-spectrum antibiotics (100 %), hydration (100 %), analgesics (43.2 %), whole blood transfusion (66.7 %), and oxygen supplementation (33.3 %). Blood transfusion significantly improved hemoglobin level (p = 0.039). The duration of hospitalization, the mean of which was 6.8 (3.1) days, was influenced by none of the tested variables (all p values > 0.05). CONCLUSION: ACS is frequent among SCD children in our milieu. Its etiologies seem to be multifactorial. Patients’ parents should be educated to recognize early signs and symptoms of the disease, and consult rapidly. Additionally, clinicians must be trained to diagnose ACS, and manage it promptly and efficiently to avoid its related catastrophic consequences.",2015 Sep 21,"['Nansseu, Jobert Richie N.', 'Alima Yanda, Anastasie Nicole', 'Chelo, David', 'Tatah, Sandra A.', 'Mbassi Awa, Hubert D.', 'Seungue, Judith', 'Koki, Paul Olivier N.']",BMC Pediatr,,,True
76dcc76a0d6041517a4d88f763269bd0196488cb,PMC,"Low prevalence of equine coronavirus in foals in the largest thoroughbred horse breeding region of Japan, 2012–2014",http://dx.doi.org/10.1186/s13028-015-0149-4,PMC4579792,26395082,CC BY,"BACKGROUND: Equine coronavirus (ECoV) is considered to be a diarrheic pathogen in foals. In central Kentucky in the United States, it has been shown that approximately 30 % of thoroughbred foals are infected with ECoV and thus it is considered widely prevalent. In contrast, the epidemiology of ECoV and its relationship to diarrhea in foals are poorly understood in Japan. We investigated ECoV in rectal swabs collected from thoroughbred foals in Japan. RESULTS: We collected 337 rectal swabs from 307 diarrheic foals in the Hidaka district of Hokkaido, the largest thoroughbred horse breeding region in Japan, between 2012 and 2014. In addition, 120 rectal swabs were collected from 120 healthy foals in 2012. These samples were tested by reverse transcription loop-mediated isothermal amplification and a real-time reverse transcription-polymerase chain reaction. All samples collected from diarrheic foals were negative, and only three samples (2.5 %) collected from healthy foals were positive for ECoV. Compared with central Kentucky, ECoV is not prevalent among thoroughbred foals in the Hidaka district of Hokkaido. CONCLUSION: ECoV is not prevalent and was not related to diarrhea in thoroughbred foals in the Hidaka district of Hokkaido between 2012 and 2014.",2015 Sep 22,"['Nemoto, Manabu', 'Oue, Yasuhiro', 'Higuchi, Tohru', 'Kinoshita, Yuta', 'Bannai, Hiroshi', 'Tsujimura, Koji', 'Yamanaka, Takashi', 'Kondo, Takashi']",Acta Vet Scand,,,True
4fe4eefd0cb0263c466d4e7895fcfec52b502a21,PMC,"Knowledge, attitudes, and practices of Hong Kong population towards human A/H7N9 influenza pandemic preparedness, China, 2014",http://dx.doi.org/10.1186/s12889-015-2245-9,PMC4579795,26395243,CC BY,"BACKGROUND: Since SARS epidemic in 2003, Hong Kong has experienced several major epidemic risks, but how general community might react to the repeated infectious diseases health risks have not been studied. In 2013, imported human H7N9 influenza infected cases from China were reported. Our study aims to assess the knowledge, attitude and practice (KAP) concerning A/H7N9 among Hong Kong general population regarding pandemic preparedness in early 2014. METHODS: A cross-sectional, population-based telephone survey study was conducted among the Cantonese-speaking population aged over 15 years in Hong Kong in February 2014. The study survey was composed of 78 KAP questions. Factors associated with individual and household pandemic preparedness were analyzed. RESULTS: Final study sample was 1,020 with a response rate of 45.9 %. Among the respondents, most of them believed personal hygiene and avoidance of avian contacts were effective in preventing H7N9 infections. The majority of respondents had satisfactory hand hygiene practices and avoided touching avian species but did not employ other preventive measures. Female, 25 years old or older, white collar workers, people with chronic diseases and people living in the city center tended to report better hygiene practices. The average State-Trait Anxiety Inventory score was 1.85, similar to that of the period during the first wave and at the start of the second wave of the H7N9 epidemic. Self-reported face masks wearing when having influenza-like illness in general population dropped from 92.4 % during H5N1 period in 2007 to 39.0 % in this study. CONCLUSION: Hong Kong citizens show a low level of anxiety, misconceptions regarding the novel strains as well as gaps between perceived usefulness and practice of preventive measures towards influenza outbreaks. Educational campaigns and framing the issue to increase public and media awareness are crucial in preventing the current public fatigue towards outbreaks.",2015 Sep 22,"['Chan, Emily YY', 'Cheng, Calvin KY', 'Tam, Greta', 'Huang, Zhe', 'Lee, Poyi']",BMC Public Health,,,True
76d6014c9fac61e50caf256e5ca92ea007219c29,PMC,The 15N and 46R Residues of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Protein Enhance Regulatory T Lymphocytes Proliferation,http://dx.doi.org/10.1371/journal.pone.0138772,PMC4580451,26397116,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) negatively modulates host immune responses, resulting in persistent infection and immunosuppression. PRRSV infection increases the number of PRRSV-specific regulatory T lymphocytes (Tregs) in infected pigs. However, the target antigens for Tregs proliferation in PRRSV infection have not been fully understood. In this study, we demonstrated that the highly pathogenic PRRSV (HP-PRRSV) induced more CD4(+)CD25(+)Foxp3(+) Tregs than classical PRRSV (C-PRRSV) strain. Of the recombinant GP5, M and N proteins of HP-PRRSV expressed in baculovirus expression systems, only N protein induced Tregs proliferation. The Tregs assays showed that three amino-acid regions, 15–21, 42–48 and 88–94, in N protein played an important role in induction of Tregs proliferation with synthetic peptides covering the whole length of N protein. By using reverse genetic methods, it was firstly found that the 15N and 46R residues in PRRSV N protein were critical for induction of Tregs proliferation. The phenotype of induced Tregs closely resembled that of transforming-growth-factor-β-secreting T helper 3 Tregs in swine. These data should be useful for understanding the mechanism of immunity to PRRSV and development of infection control strategies in the future.",2015 Sep 23,"['Fan, Baochao', 'Liu, Xing', 'Bai, Juan', 'Li, Yufeng', 'Zhang, Qiaoya', 'Jiang, Ping']",PLoS One,,,True
280a11fb6a3cd27873efa93e4600bc4227e7ee0b,PMC,"Communicable Diseases Prioritized According to Their Public Health Relevance, Sweden, 2013",http://dx.doi.org/10.1371/journal.pone.0136353,PMC4580468,26397699,CC BY,"To establish strategic priorities for the Public Health Agency of Sweden we prioritized pathogens according to their public health relevance in Sweden in order to guide resource allocation. We then compared the outcome to ongoing surveillance. We used a modified prioritization method developed at the Robert Koch Institute in Germany. In a Delphi process experts scored pathogens according to ten variables. We ranked the pathogens according to the total score and divided them into four priority groups. We then compared the priority groups to self-reported time spent on surveillance by epidemiologists and ongoing programmes for surveillance through mandatory and/or voluntary notifications and for surveillance of typing results. 106 pathogens were scored. The result of the prioritization process was similar to the outcome of the prioritization in Germany. Common pathogens such as calicivirus and Influenza virus as well as blood-borne pathogens such as human immunodeficiency virus, hepatitis B and C virus, gastro-intestinal infections such as Campylobacter and Salmonella and vector-borne pathogens such as Borrelia were all in the highest priority group. 63% of time spent by epidemiologists on surveillance was spent on pathogens in the highest priority group and all pathogens in the highest priority group, except for Borrelia and varicella-zoster virus, were under surveillance through notifications. Ten pathogens in the highest priority group (Borrelia, calicivirus, Campylobacter, Echinococcus multilocularis, hepatitis C virus, HIV, respiratory syncytial virus, SARS- and MERS coronavirus, tick-borne encephalitis virus and varicella-zoster virus) did not have any surveillance of typing results. We will evaluate the possibilities of surveillance for the pathogens in the highest priority group where we currently do not have any ongoing surveillance and evaluate the need of surveillance for the pathogens from the low priority group where there is ongoing surveillance in order to focus our work on the pathogens with the highest relevance.",2015 Sep 23,"['Dahl, Viktor', 'Tegnell, Anders', 'Wallensten, Anders']",PLoS One,,,True
ee5b43d20a640664510cb7a540caaae4a8e19933,PMC,Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam,http://dx.doi.org/10.1371/journal.pone.0138138,PMC4580613,26398118,CC BY,"Building on a series of ground breaking reviews that first defined and drew attention to emerging infectious diseases (EID), the ‘convergence model’ was proposed to explain the multifactorial causality of disease emergence. The model broadly hypothesizes disease emergence is driven by the co-incidence of genetic, physical environmental, ecological, and social factors. We developed and tested a model of the emergence of highly pathogenic avian influenza (HPAI) H5N1 based on suspected convergence factors that are mainly associated with land-use change. Building on previous geospatial statistical studies that identified natural and human risk factors associated with urbanization, we added new factors to test whether causal mechanisms and pathogenic landscapes could be more specifically identified. Our findings suggest that urbanization spatially combines risk factors to produce particular types of peri-urban landscapes with significantly higher HPAI H5N1 emergence risk. The work highlights that peri-urban areas of Viet Nam have higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture than rural and urban areas. We also found that land-use diversity, a surrogate measure for potential mixing of host populations and other factors that likely influence viral transmission, significantly improves the model’s predictability. Similarly, landscapes where intensive and extensive forms of poultry production overlap were found at greater risk. These results support the convergence hypothesis in general and demonstrate the potential to improve EID prevention and control by combing geospatial monitoring of these factors along with pathogen surveillance programs.",2015 Sep 23,"['Saksena, Sumeet', 'Fox, Jefferson', 'Epprecht, Michael', 'Tran, Chinh C.', 'Nong, Duong H.', 'Spencer, James H.', 'Nguyen, Lam', 'Finucane, Melissa L.', 'Tran, Vien D.', 'Wilcox, Bruce A.']",PLoS One,,,True
73560247ea59c1db0dd80dc9022c7d6795f7d671,PMC,Environmental and Intrinsic Correlates of Stress in Free-Ranging Wolves,http://dx.doi.org/10.1371/journal.pone.0137378,PMC4580640,26398784,CC0,"BACKGROUND: When confronted with a stressor, animals react with several physiological and behavioral responses. Although sustained or repeated stress can result in severe deleterious physiological effects, the causes of stress in free-ranging animals are yet poorly documented. In our study, we aimed at identifying the main factors affecting stress levels in free-ranging wolves (Canis lupus). METHODOLOGY/PRINCIPAL FINDINGS: We used fecal cortisol metabolites (FCM) as an index of stress, after validating the method for its application in wolves. We analyzed a total of 450 fecal samples from eleven wolf packs belonging to three protected populations, in Italy (Abruzzo), France (Mercantour), and the United States (Yellowstone). We collected samples during two consecutive winters in each study area. We found no relationship between FCM concentrations and age, sex or social status of individuals. At the group level, our results suggest that breeding pair permanency and the loss of pack members through processes different from dispersal may importantly impact stress levels in wolves. We measured higher FCM levels in comparatively small packs living in sympatry with a population of free-ranging dogs. Lastly, our results indicate that FCM concentrations are associated with endoparasitic infections of individuals. CONCLUSIONS/SIGNIFICANCE: In social mammals sharing strong bonds among group members, the death of one or several members of the group most likely induces important stress in the remainder of the social unit. The potential impact of social and territorial stability on stress levels should be further investigated in free-ranging populations, especially in highly social and in territorial species. As persistent or repeated stressors may facilitate or induce pathologies and physiological alterations that can affect survival and fitness, we advocate considering the potential impact of anthropogenic causes of stress in management and conservation programs regarding wolves and other wildlife.",2015 Sep 23,"['Molnar, Barbara', 'Fattebert, Julien', 'Palme, Rupert', 'Ciucci, Paolo', 'Betschart, Bruno', 'Smith, Douglas W.', 'Diehl, Peter-Allan']",PLoS One,,,True
1679d2d946adeb59a2ce943f067d4bde57f5577d,PMC,Lack of cross-protection against Mycoplasma haemofelis infection and signs of enhancement in “Candidatus Mycoplasma turicensis”-recovered cats,http://dx.doi.org/10.1186/s13567-015-0240-x,PMC4581119,26403079,CC BY,"“Mycoplasma haemofelis” and “Candidatus Mycoplasma turicensis” are feline hemoplasmas that induce hemolytic anemia. Protection from homologous re-challenge was recently demonstrated in cats recovered from primary infection. Here, we determined if cats recovered from “Cand. M. turicensis” infection were protected against infections with the more pathogenic M. haemofelis. Ten specified pathogen-free cats were exposed to M. haemofelis. Five of the ten cats had recovered from “Cand. M. turicensis” bacteremia (group A), and five cats were naïve controls (group B). No cross-protection was observed. By contrast, the “Cand. M. turicensis”-recovered cats displayed faster M. haemofelis infection onset (earlier PCR-positive and anemic) than the controls. No “Cand. M. turicensis” was detected in any cat. M. haemofelis shedding was observed in saliva, feces and urine. In both groups, evidence of a Th1 response was observed (high IFN-γ, low IL-4), but IL-10 levels were also high. In group A, total, CD4+ and CD8+ T cells increased within days after M. haemofelis exposure. At times of maximal bacteremia, macrocytic hypochromic anemia, neutropenia, monocytosis and a decrease in leukocyte, eosinophil, and lymphocyte counts and subsets thereof (B- and T-cells, CD4+, CD8+ and CD4+CD25+ cells) were particularly significant in group A. Moreover, an increase in protein concentrations, hypoalbuminemia and a polyclonal hypergammaglobulinemia were observed. Five of ten M. haemofelis-infected cats subsequently cleared bacteremia without antibiotic treatment. In conclusion, the study suggests that a previous hemoplasma infection, even when the cat has ostensibly recovered, may influence subsequent infections, lead to an enhancement phenomenon and other differences in infection kinetics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-015-0240-x) contains supplementary material, which is available to authorized users.",2015 Sep 24,"['Baumann, Julia', 'Novacco, Marilisa', 'Willi, Barbara', 'Riond, Barbara', 'Meli, Marina L', 'Boretti, Felicitas S', 'Hofmann-Lehmann, Regina']",Vet Res,,,True
d3871c351aa5020a710d992fe726096265a1b57a,PMC,Binding of SGTA to Rpn13 selectively modulates protein quality control,http://dx.doi.org/10.1242/jcs.165209,PMC4582187,26169395,CC BY,"Rpn13 is an intrinsic ubiquitin receptor of the 26S proteasome regulatory subunit that facilitates substrate capture prior to degradation. Here we show that the C-terminal region of Rpn13 binds to the tetratricopeptide repeat (TPR) domain of SGTA, a cytosolic factor implicated in the quality control of mislocalised membrane proteins (MLPs). The overexpression of SGTA results in a substantial increase in steady-state MLP levels, consistent with an effect on proteasomal degradation. However, this effect is strongly dependent upon the interaction of SGTA with the proteasomal component Rpn13. Hence, overexpression of the SGTA-binding region of Rpn13 or point mutations within the SGTA TPR domain both inhibit SGTA binding to the proteasome and substantially reduce MLP levels. These findings suggest that SGTA can regulate the access of MLPs to the proteolytic core of the proteasome, implying that a protein quality control cycle that involves SGTA and the BAG6 complex can operate at the 19S regulatory particle. We speculate that the binding of SGTA to Rpn13 enables specific polypeptides to escape proteasomal degradation and/or selectively modulates substrate degradation.",2015 Sep 1,"['Leznicki, Pawel', 'Korac-Prlic, Jelena', 'Kliza, Katarzyna', 'Husnjak, Koraljka', 'Nyathi, Yvonne', 'Dikic, Ivan', 'High, Stephen']",J Cell Sci,,,False
9651e34f55c7182fa2aa62a57a94bdbcd31b6f24,PMC,The pro-inflammatory cytokine 14-3-3ε is a ligand of CD13 in cartilage,http://dx.doi.org/10.1242/jcs.169573,PMC4582189,26208633,CC BY,"Osteoarthritis is a whole-joint disease characterized by the progressive destruction of articular cartilage involving abnormal communication between subchondral bone and cartilage. Our team previously identified 14-3-3ε protein as a subchondral bone soluble mediator altering cartilage homeostasis. The aim of this study was to investigate the involvement of CD13 (also known as aminopeptidase N, APN) in the chondrocyte response to 14-3-3ε. After identifying CD13 in chondrocytes, we knocked down CD13 with small interfering RNA (siRNA) and blocking antibodies in articular chondrocytes. 14-3-3ε-induced MMP-3 and MMP-13 was significantly reduced with CD13 knockdown, which suggests that it has a crucial role in 14-3-3ε signal transduction. Aminopeptidase N activity was identified in chondrocytes, but the activity was unchanged after stimulation with 14-3-3ε. Direct interaction between CD13 and 14-3-3ε was then demonstrated by surface plasmon resonance. Using labeled 14-3-3ε, we also found that 14-3-3ε binds to the surface of chondrocytes in a manner that is dependent on CD13. Taken together, these results suggest that 14-3-3ε might directly bind to CD13, which transmits its signal in chondrocytes to induce a catabolic phenotype similar to that observed in osteoarthritis. The 14-3-3ε–CD13 interaction could be a new therapeutic target in osteoarthritis.",2015 Sep 1,"['Nefla, Meriam', 'Sudre, Laure', 'Denat, Guillaume', 'Priam, Sabrina', 'Andre-Leroux, Gwenaëlle', 'Berenbaum, Francis', 'Jacques, Claire']",J Cell Sci,,,False
a969190e8cae42cb65e639aee83d71d9f78c4dc0,PMC,Determination of the infectious titer and virulence of an original US porcine epidemic diarrhea virus PC22A strain,http://dx.doi.org/10.1186/s13567-015-0249-1,PMC4582625,26408019,CC BY,"The infectious dose of a virus pool of original US PEDV strain PC22A was determined in 4-day-old, cesarean-derived, colostrum-deprived (CDCD) piglets. The median pig diarrhea dose (PDD(50)) of the virus pool was determined as 7.35 log(10) PDD(50)/mL, similar to the cell culture infectious titer, 7.75 log(10) plaque-forming units (PFU)/mL. 100 PDD(50) caused watery diarrhea in all conventional suckling piglets (n = 12) derived from a PEDV-naive sow, whereas 1000 and 10 000 PDD(50) did not cause diarrhea in piglets derived from two PEDV-field exposed-recovered sows. This information is important for future PEDV challenge studies and validation of PEDV vaccines.",2015 Sep 25,"['Liu, Xinsheng', 'Lin, Chun-Ming', 'Annamalai, Thavamathi', 'Gao, Xiang', 'Lu, Zhongyan', 'Esseili, Malak A', 'Jung, Kwonil', 'El-Tholoth, Mohamed', 'Saif, Linda J', 'Wang, Qiuhong']",Vet Res,,,True
24f4f393fb59daab089844e7af64e913d2951034,PMC,The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes,http://dx.doi.org/10.1371/journal.pone.0138075,PMC4583277,26406906,CC BY,"Pelargonium sidoides is a medical herb and respective extracts are used very frequently for the treatment of respiratory tract infections. However, the effects of Pelargonium sidoides and a special extract prepared from its roots (EPs 7630) on human immune cells are not fully understood. Here we demonstrate that EPs 7630 induced a rapid and dose-dependent production of TNF-α, IL-6, and IL-10 by human blood immune cells. This EPs 7630-induced cytokine profile was more pro-inflammatory in comparison with the profile induced by viral or bacterial infection-mimicking agents. The search for EPs 7630 target cells revealed that T-cells did not respond to EPs 7630 stimulation by production of TNF-α, IL-6, or IL-10. Furthermore, pretreatment of T-cells with EPs 7630 did not modulate their TNF-α, IL-6, and IL-10 secretion during subsequent activation. In contrast to lymphocytes, monocytes showed clear intracellular TNF-α staining after EPs 7630 treatment. Accordingly, EPs 7630 predominantly provoked activation of MAP kinases and inhibition of p38 strongly reduced the monocyte TNF-α production. The pretreatment of blood immune cells with EPs 7630 lowered their secretion of TNF-α and IL-10 and caused an IL-6 dominant response during second stimulation with viral or bacterial infection-mimicking agents. In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells.",2015 Sep 25,"['Witte, Katrin', 'Koch, Egon', 'Volk, Hans-Dieter', 'Wolk, Kerstin', 'Sabat, Robert']",PLoS One,,,True
dccf40912c6da39a0326cd025ae83d3933a1849a,PMC,New Epidemiological and Clinical Signatures of 18 Pathogens from Respiratory Tract Infections Based on a 5-Year Study,http://dx.doi.org/10.1371/journal.pone.0138684,PMC4583381,26406339,CC BY,"BACKGROUND: Respiratory tract infections (RTIs) are a heavy burden on society. However, due to the complex etiology of RTIs, the clinical diagnosis, treatment, and prevention of these infections remain challenging, especially in developing countries. METHODS: To determine the epidemiological and clinical characteristics of 18 respiratory pathogens, we analyzed 12,502 patients with acute respiratory infections (ARIs) by performing polymerase chain reaction (PCR) on patient pharyngeal swabs. RESULTS: Samples positive for at least 1 pathogen were obtained from 48.42% of the total patients. Of these pathogen-positive patients, 17.99% were infected with more than 1 pathogen. Of the 18 pathogens analyzed, four were detected with a positive detection rate (PDR) > 5%: influenza A virus (IAV) > respiratory syncytial virus (RSV) >Mycoplasma pneumoniae (MP) > human coronavirus (HCoV). The pathogens with the 4 highest co-infection rates (CIRs) were as follows: HCoV > human bocavirus (HBoV) > enterovirus (EV) > parainfluenza virus (PIV). The overall positive detection rate (PDR) varied significantly according to patient age, the season and year of detection, and the disease subgroup, but not according to patient sex. The individual PDRs of the pathogens followed 3 types of distributions for patient sex, 4 types of distributions for patient age, 4 types of seasonal distributions, 2 types of seasonal epidemic trends, 4 types of yearly epidemic trends, and different susceptibility distributions in the disease subgroups. Additionally, the overall CIR showed significantly different distributions according to patient sex, patient age, and the disease subgroup, whereas the CIRs of individual pathogens suggested significant preference characteristics. CONCLUSION: IAV remains the most common pathogen among the pathogens analyzed. More effort should be directed toward the prevention and control of pathogens that show a trend of increasing incidence such as HCoV, human adenovirus (ADV), and RSV. Although clinically distinguishing specific pathogens responsible for RTIs is difficult, the epidemiological and clinical characteristics of the various RTI-causing agents could provide clues for clinicians, thereby informing decisions regarding prevention and medication and guiding appropriate public health strategies.",2015 Sep 25,"['Liao, Xiaohong', 'Hu, Zhengbo', 'Liu, Wenkuan', 'Lu, Yan', 'Chen, Dehui', 'Chen, Meixin', 'Qiu, Shuyan', 'Zeng, Zhiqi', 'Tian, Xingui', 'Cui, Hong', 'Zhou, Rong']",PLoS One,,,True
a5360f18c21cf7f9a04e9b21663301b4548eadd9,PMC,A Multiple siRNA-Based Anti-HIV/SHIV Microbicide Shows Protection in Both In Vitro and In Vivo Models,http://dx.doi.org/10.1371/journal.pone.0135288,PMC4583459,26407080,CC0,"Human immunodeficiency virus (HIV) types 1 and 2 (HIV-1 and HIV-2) are the etiologic agents of AIDS. Most HIV-1 infected individuals worldwide are women, who acquire HIV infections during sexual contact. Blocking HIV mucosal transmission and local spread in the female lower genital tract is important in preventing infection and ultimately eliminating the pandemic. Microbicides work by destroying the microbes or preventing them from establishing an infection. Thus, a number of different types of microbicides are under investigation, however, the lack of their solubility and bioavailability, and toxicity has been major hurdles. Herein, we report the development of multifunctional chitosan-lipid nanocomplexes that can effectively deliver plasmids encoding siRNA(s) as microbicides without adverse effects and provide significant protection against HIV in both in vitro and in vivo models. Chitosan or chitosan-lipid (chlipid) was complexed with a cocktail of plasmids encoding HIV-1-specific siRNAs (psiRNAs) and evaluated for their efficacy in HEK-293 cells, PBMCs derived from nonhuman primates, 3-dimensional human vaginal ectocervical tissue (3D-VEC) model and also in non-human primate model. Moreover, prophylactic administration of the chlipid to deliver a psiRNA cocktail intravaginally with a cream formulation in a non-human primate model showed substantial reduction of SHIV (simian/human immunodeficiency virus SF162) viral titers. Taken together, these studies demonstrate the potential of chlipid-siRNA nanocomplexes as a potential genetic microbicide against HIV infections.",2015 Sep 25,"['Boyapalle, Sandhya', 'Xu, Weidong', 'Raulji, Payal', 'Mohapatra, Subhra', 'Mohapatra, Shyam S']",PLoS One,,,True
8feaa6f0bac0c30c9b3cf6634082e8923d99b070,PMC,Modulation of the Host Lipid Landscape to Promote RNA Virus Replication: The Picornavirus Encephalomyocarditis Virus Converges on the Pathway Used by Hepatitis C Virus,http://dx.doi.org/10.1371/journal.ppat.1005185,PMC4583462,26406250,CC BY,"Cardioviruses, including encephalomyocarditis virus (EMCV) and the human Saffold virus, are small non-enveloped viruses belonging to the Picornaviridae, a large family of positive-sense RNA [(+)RNA] viruses. All (+)RNA viruses remodel intracellular membranes into unique structures for viral genome replication. Accumulating evidence suggests that picornaviruses from different genera use different strategies to generate viral replication organelles (ROs). For instance, enteroviruses (e.g. poliovirus, coxsackievirus, rhinovirus) rely on the Golgi-localized phosphatidylinositol 4-kinase III beta (PI4KB), while cardioviruses replicate independently of the kinase. By which mechanisms cardioviruses develop their ROs is currently unknown. Here we show that cardioviruses manipulate another PI4K, namely the ER-localized phosphatidylinositol 4-kinase III alpha (PI4KA), to generate PI4P-enriched ROs. By siRNA-mediated knockdown and pharmacological inhibition, we demonstrate that PI4KA is an essential host factor for EMCV genome replication. We reveal that the EMCV nonstructural protein 3A interacts with and is responsible for PI4KA recruitment to viral ROs. The ensuing phosphatidylinositol 4-phosphate (PI4P) proved important for the recruitment of oxysterol-binding protein (OSBP), which delivers cholesterol to EMCV ROs in a PI4P-dependent manner. PI4P lipids and cholesterol are shown to be required for the global organization of the ROs and for viral genome replication. Consistently, inhibition of OSBP expression or function efficiently blocked EMCV RNA replication. In conclusion, we describe for the first time a cellular pathway involved in the biogenesis of cardiovirus ROs. Remarkably, the same pathway was reported to promote formation of the replication sites of hepatitis C virus, a member of the Flaviviridae family, but not other picornaviruses or flaviviruses. Thus, our results highlight the convergent recruitment by distantly related (+)RNA viruses of a host lipid-modifying pathway underlying formation of viral replication sites.",2015 Sep 25,"['Dorobantu, Cristina M.', 'Albulescu, Lucian', 'Harak, Christian', 'Feng, Qian', 'van Kampen, Mirjam', 'Strating, Jeroen R. P. M.', 'Gorbalenya, Alexander E.', 'Lohmann, Volker', 'van der Schaar, Hilde M.', 'van Kuppeveld, Frank J. M.']",PLoS Pathog,,,True
daeba3efafc5b3f9e71e38069aadf1e0178bac9d,PMC,Challenges of the Unknown: Clinical Application of Microbial Metagenomics,http://dx.doi.org/10.1155/2015/292950,PMC4584244,26451363,CC BY,"Availability of fast, high throughput and low cost whole genome sequencing holds great promise within public health microbiology, with applications ranging from outbreak detection and tracking transmission events to understanding the role played by microbial communities in health and disease. Within clinical metagenomics, identifying microorganisms from a complex and host enriched background remains a central computational challenge. As proof of principle, we sequenced two metagenomic samples, a known viral mixture of 25 human pathogens and an unknown complex biological model using benchtop technology. The datasets were then analysed using a bioinformatic pipeline developed around recent fast classification methods. A targeted approach was able to detect 20 of the viruses against a background of host contamination from multiple sources and bacterial contamination. An alternative untargeted identification method was highly correlated with these classifications, and over 1,600 species were identified when applied to the complex biological model, including several species captured at over 50% genome coverage. In summary, this study demonstrates the great potential of applying metagenomics within the clinical laboratory setting and that this can be achieved using infrastructure available to nondedicated sequencing centres.",2015 Sep 14,"['Rose, Graham', 'Wooldridge, David J.', 'Anscombe, Catherine', 'Mee, Edward T.', 'Misra, Raju V.', 'Gharbia, Saheer']",Int J Genomics,,,True
4d2e434006533cb3bbb701dffb53169b40a9c315,PMC,Viral Mimicry to Usurp Ubiquitin and SUMO Host Pathways,http://dx.doi.org/10.3390/v7092849,PMC4584293,26343706,CC BY,"Posttranslational modifications (PTMs) of proteins include enzymatic changes by covalent addition of cellular regulatory determinants such as ubiquitin (Ub) and small ubiquitin-like modifier (SUMO) moieties. These modifications are widely used by eukaryotic cells to control the functional repertoire of proteins. Over the last decade, it became apparent that the repertoire of ubiquitiylation and SUMOylation regulating various biological functions is not restricted to eukaryotic cells, but is also a feature of human virus families, used to extensively exploit complex host-cell networks and homeostasis. Intriguingly, besides binding to host SUMO/Ub control proteins and interfering with the respective enzymatic cascade, many viral proteins mimic key regulatory factors to usurp this host machinery and promote efficient viral outcomes. Advanced detection methods and functional studies of ubiquitiylation and SUMOylation during virus-host interplay have revealed that human viruses have evolved a large arsenal of strategies to exploit these specific PTM processes. In this review, we highlight the known viral analogs orchestrating ubiquitin and SUMO conjugation events to subvert and utilize basic enzymatic pathways.",2015 Aug 28,"['Wimmer, Peter', 'Schreiner, Sabrina']",Viruses,,,True
608a7194b225bedf27e124dfbe8f2acecbca587f,PMC,"Exosome Biogenesis, Regulation, and Function in Viral Infection",http://dx.doi.org/10.3390/v7092862,PMC4584306,26393640,CC BY,"Exosomes are extracellular vesicles released upon fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. They originate as intraluminal vesicles (ILVs) during the process of MVB formation. Exosomes were shown to contain selectively sorted functional proteins, lipids, and RNAs, mediating cell-to-cell communications and hence playing a role in the physiology of the healthy and diseased organism. Challenges in the field include the identification of mechanisms sustaining packaging of membrane-bound and soluble material to these vesicles and the understanding of the underlying processes directing MVBs for degradation or fusion with the plasma membrane. The investigation into the formation and roles of exosomes in viral infection is in its early years. Although still controversial, exosomes can, in principle, incorporate any functional factor, provided they have an appropriate sorting signal, and thus are prone to viral exploitation. This review initially focuses on the composition and biogenesis of exosomes. It then explores the regulatory mechanisms underlying their biogenesis. Exosomes are part of the endocytic system, which is tightly regulated and able to respond to several stimuli that lead to alterations in the composition of its sub-compartments. We discuss the current knowledge of how these changes affect exosomal release. We then summarize how different viruses exploit specific proteins of endocytic sub-compartments and speculate that it could interfere with exosome function, although no direct link between viral usage of the endocytic system and exosome release has yet been reported. Many recent reports have ascribed functions to exosomes released from cells infected with a variety of animal viruses, including viral spread, host immunity, and manipulation of the microenvironment, which are discussed. Given the ever-growing roles and importance of exosomes in viral infections, understanding what regulates their composition and levels, and defining their functions will ultimately provide additional insights into the virulence and persistence of infections.",2015 Sep 17,"['Alenquer, Marta', 'Amorim, Maria João']",Viruses,,,True
48c20fe82a21edeefb8e1966189db32213a446fc,PMC,Tight Junctions Go Viral!,http://dx.doi.org/10.3390/v7092865,PMC4584309,26404354,CC BY,"Tight junctions (TJs) are highly specialized membrane domains involved in many important cellular processes such as the regulation of the passage of ions and macromolecules across the paracellular space and the establishment of cell polarity in epithelial cells. Over the past few years there has been increasing evidence that different components of the TJs can be hijacked by viruses in order to complete their infectious cycle. Viruses from at least nine different families of DNA and RNA viruses have been reported to use TJ proteins in their benefit. For example, TJ proteins such as JAM-A or some members of the claudin family of proteins are used by members of the Reoviridae family and hepatitis C virus as receptors or co-receptors during their entry into their host cells. Reovirus, in addition, takes advantage of the TJ protein Junction Adhesion Molecule-A (JAM-A) to achieve its hematogenous dissemination. Some other viruses are capable of regulating the expression or the localization of TJ proteins to induce cell transformation or to improve the efficiency of their exit process. This review encompasses the importance of TJs for viral entry, replication, dissemination, and egress, and makes a clear statement of the importance of studying these proteins to gain a better understanding of the replication strategies used by viruses that infect epithelial and/or endothelial cells.",2015 Sep 23,"['Torres-Flores, Jesús M.', 'Arias, Carlos F.']",Viruses,,,True
f057fa2845067210cbd31e79d8a83cdff0aa96f1,PMC,Interferon lambda inhibits dengue virus replication in epithelial cells,http://dx.doi.org/10.1186/s12985-015-0383-4,PMC4584467,26411318,CC BY,"BACKGROUND: In viral disease, infection is controlled at the cellular level by type I interferon (IFN-I), but dengue virus (DENV) has the ability to inhibit this response. Type III interferon, also known as lambda IFN (IFN-III or IFN-λ), is a complementary pathway to the antiviral response by IFN-I. This work analyzed the IFN-λ (IFN-III) mediated antiviral response against DENV serotype 2 (DENV-2) infection. METHODS: Dengue fever patients were sampled to determine their IFN-λ levels by ELISA. To study the IFN-λ response during DENV infection we selected the epithelial cell line C33-A, and we demonstrated that it is permissive to DENV-2 infection. The effect of IFN-λ on virus replication was determined in these cells, in parallel to the expression of IFN-stimulated genes (ISGs), and Suppressor of Cytokine Signaling (SOCS), genes measured by RT-qPCR. RESULTS: We found increased (~1.8 times) serological IFN-λ in dengue fever patients compared to healthy blood donors. IFN-λ inhibited DENV-2 replication in a dose-dependent manner in vitro. The reduction of viral titer corresponded with increased ISG mRNA levels (MX1 and OAS1), with the highest inhibition occurring at ISG’s peak expression. Presence of IFN-negative regulators, SOCS1 and SOCS3, during DENV-2 infection was associated with reduced IFN-λ1 expression. CONCLUSIONS: Evidence described here suggests that IFN-λ is a good candidate inhibitor of viral replication in dengue infection. Mechanisms for the cellular and organismal interplay between DENV and IFN- λ need to be further studied as they could provide insights into strategies to treat this disease. Furthermore, we report a novel epithelial model to study dengue infection in vitro.",2015 Sep 28,"['Palma-Ocampo, Helen K.', 'Flores-Alonso, Juan C.', 'Vallejo-Ruiz, Verónica', 'Reyes-Leyva, Julio', 'Flores-Mendoza, Lilian', 'Herrera-Camacho, Irma', 'Rosas-Murrieta, Nora H.', 'Santos-López, Gerardo']",Virol J,,,True
3d0d60d3d1906b4086ca3e10bcf5dde7b4db69b8,PMC,Disruptive Innovation Can Prevent the Next Pandemic,http://dx.doi.org/10.3389/fpubh.2015.00215,PMC4585064,26442242,CC BY,"Public health surveillance (PHS) is at a tipping point, where the application of novel processes, technologies, and tools promise to vastly improve efficiency and effectiveness. Yet twentieth century, entrenched ideology and lack of training results in slow uptake and resistance to change. The term disruptive innovation – used to describe advances in technology and processes that change existing markets – is useful to describe the transformation of PHS. Past disruptive innovations used in PHS, such as distance learning, the smart phone, and field-based laboratory testing have outpaced older services, practices, and technologies used in the traditional classroom, governmental offices, and personal communication, respectively. Arguably, the greatest of these is the Internet – an infrastructural innovation that continues to enable exponential benefits in seemingly limitless ways. Considering the Global Health Security Agenda and facing emerging and reemerging infectious disease threats, evolving environmental and behavioral risks, and ever changing epidemiologic trends, PHS must transform. Embracing disruptive innovation in the structures and processes of PHS can be unpredictable. However, it is necessary to strengthen and unlock the potential to prevent, detect, and respond.",2015 Sep 23,"['Shaikh, Affan T.', 'Ferland, Lisa', 'Hood-Cree, Robert', 'Shaffer, Loren', 'McNabb, Scott J. N.']",Front Public Health,,,True
595582a254c921f28d7c5cb9cb42e1dcabff7108,PMC,"Rapid detection of Acinetobacter baumannii and molecular epidemiology of carbapenem-resistant A. baumannii in two comprehensive hospitals of Beijing, China",http://dx.doi.org/10.3389/fmicb.2015.00997,PMC4585070,26441924,CC BY,"Acinetobacter baumannii is an important opportunistic pathogen associated with a variety of nosocomial infections. A rapid and sensitive molecular detection in clinical isolates is quite needed for the appropriate therapy and outbreak control of A. baumannii. Group 2 carbapenems have been considered the agents of choice for the treatment of multiple drug-resistant A. baumannii. But the prevalence of carbapenem-resistant A. baumannii (CRAB) has been steadily increasing in recent years. Here, we developed a loop-mediated isothermal amplification (LAMP) assay for the rapid detection of A. baumannii in clinical samples by using high-specificity primers of the bla(OXA-51) gene. Then we investigated the OXA-carbapenemases molecular epidemiology of A. baumannii isolates in two comprehensive hospitals in Beijing. The results showed that the LAMP assay could detect target DNA within 60 min at 65°C. The detection limit was 50 pg/μl, which was about 10-fold greater than that of PCR. Furthermore, this method could distinguish A. baumannii from the homologous A. nosocomialis and A. pittii. A total of 228 positive isolates were identified by this LAMP-based method for A. baumannii from 335 intensive care unit patients with clinically suspected multi-resistant infections in two hospitals in Beijing. The rates of CRAB are on the rise and are slowly becoming a routine phenotype for A. baumannii. Among the CRABs, 92.3% harbored both the bla(OXA-23) and bla(OXA-51) genes. Thirty-three pulsotypes were identified by pulsed-field gel electrophoresis, and the majority belonged to clone C. In conclusion, the LAMP method developed for detecting A. baumannii was faster and simpler than conventional PCR and has great potential for both point-of-care testing and basic research. We further demonstrated a high distribution of class D carbapenemase-encoding genes, mainly OXA-23, which presents an emerging threat in hospitals in China.",2015 Sep 23,"['Li, Puyuan', 'Niu, Wenkai', 'Li, Huan', 'Lei, Hong', 'Liu, Wei', 'Zhao, Xiangna', 'Guo, Leijing', 'Zou, Dayang', 'Yuan, Xin', 'Liu, Huiying', 'Yuan, Jing', 'Bai, Changqing']",Front Microbiol,,,True
7110b46076a08c546102c3501ab5220f96e78708,PMC,Dipeptidyl Peptidase-4 Regulation of SDF-1/CXCR4 Axis: Implications for Cardiovascular Disease,http://dx.doi.org/10.3389/fimmu.2015.00477,PMC4585326,26441982,CC BY,"Dipeptidyl peptidase-4 (DPP4) is a ubiquitously expressed protease that regulates diverse number of physiological functions. As a dipeptidase, it exerts its catalytic effects on proteins/peptides with proline, alanine, or serine in the penultimate (P1) amino acid residue from the amino terminus. The evidence to date supports an important effect of DPP4 in catalytic cleavage of incretin peptides and this perhaps represents the main mechanism by which DPP4 inhibition improves glycemic control. DPP4 also plays an important role in the degradation of multiple chemokines of which stromal cell-derived factor-1 (SDF-1, also known as CXCL12) is perhaps an increasingly recognized target, given its importance in processes, such as hematopoiesis, angiogenesis, and stem cell homing. In the current review, we will summarize the importance of DPP4-mediated enzymatic processing of cytokines/chemokines with an emphasis on SDF-1 and resultant implications for cardiovascular physiology and disease.",2015 Sep 25,"['Zhong, Jixin', 'Rajagopalan, Sanjay']",Front Immunol,,,True
7e73ff88b8e995535a2783a7ba78a743afd557a8,PMC,The heptad repeat region is a major selection target in MERS-CoV and related coronaviruses,http://dx.doi.org/10.1038/srep14480,PMC4585914,26404138,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) originated in bats and spread to humans via zoonotic transmission from camels. We analyzed the evolution of the spike (S) gene in betacoronaviruses (betaCoVs) isolated from different mammals, in bat coronavirus populations, as well as in MERS-CoV strains from the current outbreak. Results indicated several positively selected sites located in the region comprising the two heptad repeats (HR1 and HR2) and their linker. Two sites (R652 and V1060) were positively selected in the betaCoVs phylogeny and correspond to mutations associated with expanded host range in other coronaviruses. During the most recent evolution of MERS-CoV, adaptive mutations in the HR1 (Q/R/H1020) arose in camels or in a previous host and spread to humans. We determined that different residues at position 1020 establish distinct inter- and intra-helical interactions and affect the stability of the six-helix bundle formed by the HRs. A similar effect on stability was observed for a nearby mutation (T1015N) that increases MERS-CoV infection efficiency in vitro. Data herein indicate that the heptad repeat region was a major target of adaptive evolution in MERS-CoV-related viruses; these results are relevant for the design of fusion inhibitor peptides with antiviral function.",2015 Sep 25,"['Forni, Diego', 'Filippi, Giulia', 'Cagliani, Rachele', 'De Gioia, Luca', 'Pozzoli, Uberto', 'Al-Daghri, Nasser', 'Clerici, Mario', 'Sironi, Manuela']",Sci Rep,,,True
700dd02a9da7cdbddb49e21feafe8dad7985a7a3,PMC,The heptad repeat region is a major selection target in MERS-CoV and related coronaviruses,http://dx.doi.org/10.1038/srep14480,PMC4585914,26404138,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) originated in bats and spread to humans via zoonotic transmission from camels. We analyzed the evolution of the spike (S) gene in betacoronaviruses (betaCoVs) isolated from different mammals, in bat coronavirus populations, as well as in MERS-CoV strains from the current outbreak. Results indicated several positively selected sites located in the region comprising the two heptad repeats (HR1 and HR2) and their linker. Two sites (R652 and V1060) were positively selected in the betaCoVs phylogeny and correspond to mutations associated with expanded host range in other coronaviruses. During the most recent evolution of MERS-CoV, adaptive mutations in the HR1 (Q/R/H1020) arose in camels or in a previous host and spread to humans. We determined that different residues at position 1020 establish distinct inter- and intra-helical interactions and affect the stability of the six-helix bundle formed by the HRs. A similar effect on stability was observed for a nearby mutation (T1015N) that increases MERS-CoV infection efficiency in vitro. Data herein indicate that the heptad repeat region was a major target of adaptive evolution in MERS-CoV-related viruses; these results are relevant for the design of fusion inhibitor peptides with antiviral function.",2015 Sep 25,"['Forni, Diego', 'Filippi, Giulia', 'Cagliani, Rachele', 'De Gioia, Luca', 'Pozzoli, Uberto', 'Al-Daghri, Nasser', 'Clerici, Mario', 'Sironi, Manuela']",Sci Rep,,,False
bd1d9c526a0194d356d7a65ebcebc322dd872a36,PMC,Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg?,http://dx.doi.org/10.3390/nu7095350,PMC4586545,26371035,CC BY,"In the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD) and immunoglobulin deficiencies. For this purpose, we conducted a literature search on the main medical databases. SNCD poses a diagnostic dilemma. Villous blunting, intraepithelial lymphocytes (IELs) count and gluten “challenge” are the most reliable markers. Immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of SNCD patients may be useful. In our experience, tTG-mRNA was similarly increased in seropositive celiac disease (CD) and suspected SNCD, and strongly correlated with the IELs count. This increase is found even in the IELs’ range of 15–25/100 enterocytes, suggesting that there may be a “grey zone” of gluten-related disorders. An immune deregulation (severely lacking B-cell differentiation) underlies the association of SNCD with immunoglobulin deficiencies. Therefore, CD may be linked to autoimmune disorders and immune deficits (common variable immunodeficiency (CVID)/IgA selective deficiency). CVID is a heterogeneous group of antibodies dysfunction, whose association with CD is demonstrated only by the response to a gluten-free diet (GFD). We hypothesized a familial inheritance between CD and CVID. Selective IgA deficiency, commonly associated with CD, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD) is rare (<300 cases) and associated to CD in 5% of cases. We diagnosed SNCD in a patient affected by sIgMD using the tTG-mRNA assay. One-year GFD induced IgM restoration. This evidence, supporting a link between SNCD and immunoglobulin deficiencies, suggests that we should take a closer look at this association.",2015 Sep 8,"['Giorgio, Floriana', 'Principi, Mariabeatrice', 'Losurdo, Giuseppe', 'Piscitelli, Domenico', 'Iannone, Andrea', 'Barone, Michele', 'Amoruso, Annacinzia', 'Ierardi, Enzo', 'Di Leo, Alfredo']",Nutrients,,,True
3ceddc72c46d0c69ff2718e3780a0d987da91cab,PMC,"Infectious Diseases, Urbanization and Climate Change: Challenges in Future China",http://dx.doi.org/10.3390/ijerph120911025,PMC4586659,26371017,CC BY,"China is one of the largest countries in the world with nearly 20% of the world’s population. There have been significant improvements in economy, education and technology over the last three decades. Due to substantial investments from all levels of government, the public health system in China has been improved since the 2003 severe acute respiratory syndrome (SARS) outbreak. However, infectious diseases still remain a major population health issue and this may be exacerbated by rapid urbanization and unprecedented impacts of climate change. This commentary aims to explore China’s current capacity to manage infectious diseases which impair population health. It discusses the existing disease surveillance system and underscores the critical importance of strengthening the system. It also explores how the growing migrant population, dramatic changes in the natural landscape following rapid urbanization, and changing climatic conditions can contribute to the emergence and re-emergence of infectious disease. Continuing research on infectious diseases, urbanization and climate change may inform the country’s capacity to deal with emerging and re-emerging infectious diseases in the future.",2015 Sep 7,"['Tong, Michael Xiaoliang', 'Hansen, Alana', 'Hanson-Easey, Scott', 'Cameron, Scott', 'Xiang, Jianjun', 'Liu, Qiyong', 'Sun, Yehuan', 'Weinstein, Philip', 'Han, Gil-Soo', 'Williams, Craig', 'Bi, Peng']",Int J Environ Res Public Health,,,True
aaf76d77eb09c00e78926e76d0e9644a3d472161,PMC,Model Selection and Evaluation Based on Emerging Infectious Disease Data Sets including A/H1N1 and Ebola,http://dx.doi.org/10.1155/2015/207105,PMC4586906,26451161,CC BY,"The aim of the present study is to apply simple ODE models in the area of modeling the spread of emerging infectious diseases and show the importance of model selection in estimating parameters, the basic reproduction number, turning point, and final size. To quantify the plausibility of each model, given the data and the set of four models including Logistic, Gompertz, Rosenzweg, and Richards models, the Bayes factors are calculated and the precise estimates of the best fitted model parameters and key epidemic characteristics have been obtained. In particular, for Ebola the basic reproduction numbers are 1.3522 (95% CI (1.3506, 1.3537)), 1.2101 (95% CI (1.2084, 1.2119)), 3.0234 (95% CI (2.6063, 3.4881)), and 1.9018 (95% CI (1.8565, 1.9478)), the turning points are November 7,November 17, October 2, and November 3, 2014, and the final sizes until December 2015 are 25794 (95% CI (25630, 25958)), 3916 (95% CI (3865, 3967)), 9886 (95% CI (9740, 10031)), and 12633 (95% CI (12515, 12750)) for West Africa, Guinea, Liberia, and Sierra Leone, respectively. The main results confirm that model selection is crucial in evaluating and predicting the important quantities describing the emerging infectious diseases, and arbitrarily picking a model without any consideration of alternatives is problematic.",2015 Sep 15,"['Liu, Wendi', 'Tang, Sanyi', 'Xiao, Yanni']",Comput Math Methods Med,,,True
4bdb53b23deb0bc56d0aa7b26551ab76b1fd082e,PMC,"Real-time characterization of risks of death associated with the Middle East respiratory syndrome (MERS) in the Republic of Korea, 2015",http://dx.doi.org/10.1186/s12916-015-0468-3,PMC4588253,26420593,CC BY,"BACKGROUND: An outbreak of the Middle East respiratory syndrome (MERS), comprising 185 cases linked to healthcare facilities, occurred in the Republic of Korea from May to July 2015. Owing to the nosocomial nature of the outbreak, it is particularly important to gain a better understanding of the epidemiological determinants characterizing the risk of MERS death in order to predict the heterogeneous risk of death in medical settings. METHODS: We have devised a novel statistical model that identifies the risk of MERS death during the outbreak in real time. While accounting for the time delay from illness onset to death, risk factors for death were identified using a linear predictor tied to a logit model. We employ this approach to (1) quantify the risks of death and (2) characterize the temporal evolution of the case fatality ratio (CFR) as case ascertainment greatly improved during the course of the outbreak. RESULTS: Senior persons aged 60 years or over were found to be 9.3 times (95 % confidence interval (CI), 5.3–16.9) more likely to die compared to younger MERS cases. Patients under treatment were at a 7.8-fold (95 % CI, 4.0–16.7) significantly higher risk of death compared to other MERS cases. The CFR among patients aged 60 years or older under treatment was estimated at 48.2 % (95 % CI, 35.2–61.3) as of July 31, 2015, while the CFR among other cases was estimated to lie below 15 %. From June 6, 2015, onwards, the CFR declined 0.3-fold (95 % CI, 0.1–1.1) compared to the earlier epidemic period, which may perhaps reflect enhanced case ascertainment following major contact tracing efforts. CONCLUSIONS: The risk of MERS death was significantly associated with older age as well as treatment for underlying diseases after explicitly adjusting for the delay between illness onset and death. Because MERS outbreaks are greatly amplified in the healthcare setting, enhanced infection control practices in medical facilities should strive to shield risk groups from MERS exposure.",2015 Sep 30,"['Mizumoto, Kenji', 'Endo, Akira', 'Chowell, Gerardo', 'Miyamatsu, Yuichiro', 'Saitoh, Masaya', 'Nishiura, Hiroshi']",BMC Med,,,True
a9075cf8e6853657941c799058d329b3e386fecd,PMC,Recovering full-length viral genomes from metagenomes,http://dx.doi.org/10.3389/fmicb.2015.01069,PMC4589665,26483782,CC BY,"Infectious disease metagenomics is driven by the question: “what is causing the disease?” in contrast to classical metagenome studies which are guided by “what is out there?” In case of a novel virus, a first step to eventually establishing etiology can be to recover a full-length viral genome from a metagenomic sample. However, retrieval of a full-length genome of a divergent virus is technically challenging and can be time-consuming and costly. Here we discuss different assembly and fragment linkage strategies such as iterative assembly, motif searches, k-mer frequency profiling, coverage profile binning, and other strategies used to recover genomes of potential viral pathogens in a timely and cost-effective manner.",2015 Oct 1,"['Smits, Saskia L.', 'Bodewes, Rogier', 'Ruiz-González, Aritz', 'Baumgärtner, Wolfgang', 'Koopmans, Marion P.', 'Osterhaus, Albert D. M. E.', 'Schürch, Anita C.']",Front Microbiol,,,True
0910e151cd1fb8d455e54cd4e97f867627f934c8,PMC,Disparities in Spatial Prevalence of Feline Retroviruses due to Data Aggregation: A Case of the Modifiable Areal Unit Problem,http://dx.doi.org/10.1155/2014/424138,PMC4590838,26464932,CC BY,"The knowledge of the spatial distribution feline immunodeficiency virus and feline leukemia virus infections, which are untreatable, can inform on their risk factors and high-risk areas to enhance control. However, when spatial analysis involves aggregated spatial data, results may be influenced by the spatial scale of aggregation, an effect known as the modifiable areal unit problem (MAUP). In this study, area level risk factors for both infections in 28,914 cats tested with ELISA were investigated by multivariable spatial Poisson regression models along with MAUP effect on spatial clustering and cluster detection (for postal codes, counties, and states) by Moran's I test and spatial scan test, respectively. The study results indicate that the significance and magnitude of the association of risk factors with both infections varied with aggregation scale. Further more, Moran's I test only identified spatial clustering at postal code and county levels of aggregation. Similarly, the spatial scan test indicated that the number, size, and location of clusters varied over aggregation scales. In conclusion, the association between infection and area was influenced by the choice of spatial scale and indicates the importance of study design and data analysis with respect to specific research questions.",2014 Feb 19,"['Chhetri, Bimal K.', 'Berke, Olaf', 'Pearl, David L.', 'Bienzle, Dorothee']",J Vet Med,,,True
c3868e20a756883f97b18c851e9e6df7ad0cb11e,PMC,"Adenovirus infection in children with acute lower respiratory tract infections in Beijing, China, 2007 to 2012",http://dx.doi.org/10.1186/s12879-015-1126-2,PMC4591558,26429778,CC BY,"BACKGROUND: Human adenoviruses (HAdV) play a significant role in pediatric respiratory tract infections. To date, over 60 types of HAdV have been identified. Here, HAdV types are characterized in children in the Beijing area with acute lower respiratory tract infections (ALRTIs) and the clinical features and laboratory findings of hospitalized HAdV-infected cases are described. METHODS: Respiratory specimens were collected from pediatric patients with ALRTIs in the emergency department or from those admitted to Beijing Children’s Hospital between March 2007 and December 2012. Infections with common respiratory viruses were determined by PCR or RT-PCR. HAdV positive samples were further typed by PCR and sequencing. RESULTS: Among 3356 patients with ALRTIs, 194 (5.8 %) were found to have HAdV infection. HAdV infection was primarily confined to children (88.35 %) less than 5 years of age. A total of 11 different types of HAdV were detected throughout the study period, with HAdV-B7 (49.0 %) and HAdV-B3 (26.3 %) as the most prevalent types, followed by HAdV-C2 (7.7 %) and HAdVC1 (4.6 %). Newly emerging and re-emergent types or variants, HAdV-B55 (n = 5), HAdV-C57 (n = 3), and HAdV-B14p1 (n = 1), were identified. Results also included the reported first case of co-infection with HAdV-C2 and HAdV-C57. Clinical entities of patients with single HAdV infection (n = 49) were similar to those with mixed HAdV/respiratory syncytial virus (RSV) infections (n = 41). Patients with HAdV-B7 infection had longer duration of fever and higher serum levels of muscle enzymes than HAdV-B3-infected patients. CONCLUSIONS: During the study period, HAdV-B7 and HAdV-B3 were the predominant types identified in pediatric ALRTIs. HAdV-B7 infection tends to have more severe clinical consequences. The presence of newly emerging types or variants and co-infection with different types of HAdV highlights the need for constant and close surveillance of HAdV infection.",2015 Oct 1,"['Liu, Chunyan', 'Xiao, Yan', 'Zhang, Jing', 'Ren, Lili', 'Li, Jianguo', 'Xie, Zhengde', 'Xu, Baoping', 'Yang, Yan', 'Qian, Suyun', 'Wang, Jianwei', 'Shen, Kunling']",BMC Infect Dis,,,True
b973a418c19776904cffc71357c7119485bf2b3a,PMC,The Large Scale Machine Learning in an Artificial Society: Prediction of the Ebola Outbreak in Beijing,http://dx.doi.org/10.1155/2015/531650,PMC4592709,26457078,CC BY,"Ebola virus disease (EVD) distinguishes its feature as high infectivity and mortality. Thus, it is urgent for governments to draw up emergency plans against Ebola. However, it is hard to predict the possible epidemic situations in practice. Luckily, in recent years, computational experiments based on artificial society appeared, providing a new approach to study the propagation of EVD and analyze the corresponding interventions. Therefore, the rationality of artificial society is the key to the accuracy and reliability of experiment results. Individuals' behaviors along with travel mode directly affect the propagation among individuals. Firstly, artificial Beijing is reconstructed based on geodemographics and machine learning is involved to optimize individuals' behaviors. Meanwhile, Ebola course model and propagation model are built, according to the parameters in West Africa. Subsequently, propagation mechanism of EVD is analyzed, epidemic scenario is predicted, and corresponding interventions are presented. Finally, by simulating the emergency responses of Chinese government, the conclusion is finally drawn that Ebola is impossible to outbreak in large scale in the city of Beijing.",2015 Sep 20,"['Zhang, Peng', 'Chen, Bin', 'Ma, Liang', 'Li, Zhen', 'Song, Zhichao', 'Duan, Wei', 'Qiu, Xiaogang']",Comput Intell Neurosci,,,True
4277d45726b61850deb6a0a4b2cabe450127ec69,PMC,Aetiological role of common respiratory viruses in acute lower respiratory infections in children under five years: A systematic review and meta–analysis,http://dx.doi.org/10.7189/jogh.05.010408,PMC4593292,26445672,CC BY,"BACKGROUND: Acute lower respiratory infection (ALRI) remains a major cause of childhood hospitalization and mortality in young children and the causal attribution of respiratory viruses in the aetiology of ALRI is unclear. We aimed to quantify the absolute effects of these viral exposures. METHODS: We conducted a systematic literature review (across 7 databases) of case–control studies published from 1990 to 2014 which investigated the viral profile of 18592 children under 5 years with and without ALRI. We then computed a pooled odds ratio and virus–specific attributable fraction among the exposed of 8 common viruses – respiratory syncytial virus (RSV), influenza (IFV), parainfluenza (PIV), human metapneumovirus (MPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). FINDINGS: From the 23 studies included, there was strong evidence for causal attribution of RSV (OR 9.79; AFE 90%), IFV (OR 5.10; AFE 80%), PIV (OR 3.37; AFE 70%) and MPV (OR 3.76; AFE 73%), and less strong evidence for RV (OR 1.43; AFE 30%) in young children presenting with ALRI compared to those without respiratory symptoms (asymptomatic) or healthy children. However, there was no significant difference in the detection of AdV, BoV, or CoV in cases and controls. CONCLUSIONS: This review supports RSV, IFV, PIV, MPV and RV as important causes of ALRI in young children, and provides quantitative estimates of the absolute proportion of virus–associated ALRI cases to which a viral cause can be attributed.",,"['Shi, Ting', 'McLean, Kenneth', 'Campbell, Harry', 'Nair, Harish']",J Glob Health.; 5(1):010408,,,True
d49895892511c456d98567b608222314bece919d,PMC,Aetiological role of common respiratory viruses in acute lower respiratory infections in children under five years: A systematic review and meta–analysis,http://dx.doi.org/10.7189/jogh.05.010408,PMC4593292,26445672,CC BY,"BACKGROUND: Acute lower respiratory infection (ALRI) remains a major cause of childhood hospitalization and mortality in young children and the causal attribution of respiratory viruses in the aetiology of ALRI is unclear. We aimed to quantify the absolute effects of these viral exposures. METHODS: We conducted a systematic literature review (across 7 databases) of case–control studies published from 1990 to 2014 which investigated the viral profile of 18592 children under 5 years with and without ALRI. We then computed a pooled odds ratio and virus–specific attributable fraction among the exposed of 8 common viruses – respiratory syncytial virus (RSV), influenza (IFV), parainfluenza (PIV), human metapneumovirus (MPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). FINDINGS: From the 23 studies included, there was strong evidence for causal attribution of RSV (OR 9.79; AFE 90%), IFV (OR 5.10; AFE 80%), PIV (OR 3.37; AFE 70%) and MPV (OR 3.76; AFE 73%), and less strong evidence for RV (OR 1.43; AFE 30%) in young children presenting with ALRI compared to those without respiratory symptoms (asymptomatic) or healthy children. However, there was no significant difference in the detection of AdV, BoV, or CoV in cases and controls. CONCLUSIONS: This review supports RSV, IFV, PIV, MPV and RV as important causes of ALRI in young children, and provides quantitative estimates of the absolute proportion of virus–associated ALRI cases to which a viral cause can be attributed.",,"['Shi, Ting', 'McLean, Kenneth', 'Campbell, Harry', 'Nair, Harish']",J Glob Health.; 5(1):010408,,,False
2076515c446601717239a974bc7bfc84f455e62c,PMC,Siaα2-3Galβ1- Receptor Genetic Variants Are Associated with Influenza A(H1N1)pdm09 Severity,http://dx.doi.org/10.1371/journal.pone.0139681,PMC4593567,26436774,CC BY,"Different host genetic variants may be related to the virulence and transmissibility of pandemic Influenza A(H1N1)pdm09, influencing events such as binding of the virus to the entry receptor on the cell of infected individuals and the host immune response. In the present study, two genetic variants of the ST3GAL1 gene, which encodes the Siaα2-3Galβ1- receptor to which influenza A(H1N1)pdm09 virus binds for entry into the host cell, were investigated in an admixed Brazilian population. First, the six exons encoding the ST3GAL1 gene were sequenced in 68 patients infected with strain A(H1N1)pdm09. In a second phase of the study, the rs113350588 and rs1048479 polymorphisms identified in this sample were genotyped in a sample of 356 subjects from the northern and northeastern regions of Brazil with a diagnosis of pandemic influenza. Functional analysis of the polymorphisms was performed in silico and the influence of these variants on the severity of infection was evaluated. The results suggest that rs113350588 and rs1048479 may alter the function of ST3GAL1 either directly through splicing regulation alteration and/or indirectly through LD with SNP with regulatory function. In the study the rs113350588 and rs1048479 polymorphisms were in linkage disequilibrium in the population studied (D’ = 0.65). The GC haplotype was associated with an increased risk of death in subjects with influenza (OR = 4.632, 95% CI = 2.10;1.21). The AT haplotype was associated with an increased risk of severe disease and death (OR = 1.993, 95% CI = 1.09;3.61 and OR 4.476, 95% CI = 2.37;8.44, respectively). This study demonstrated for the first time the association of ST3GAL1 gene haplotypes on the risk of more severe disease and death in patients infected with Influenza A(H1N1)pdm09 virus.",2015 Oct 5,"['Maestri, Alvino', 'Sortica, Vinicius Albuquerque', 'Tovo-Rodrigues, Luciana', 'Santos, Mirleide Cordeiro', 'Barbagelata, Luana', 'Moraes, Milene Raiol', 'Alencar de Mello, Wyller', 'Gusmão, Leonor', 'Sousa, Rita Catarina Medeiros', 'Emanuel Batista dos Santos, Sidney']",PLoS One,,,True
70bae0f6fbce9a54e7574b4309c5a3ebd1be7133,PMC,Kinetic characterization of trans-proteolytic activity of Chikungunya virus capsid protease and development of a FRET-based HTS assay,http://dx.doi.org/10.1038/srep14753,PMC4593962,26439734,CC BY,"Chikungunya virus (CHIKV) capsid protein (CVCP) is a serine protease that possesses cis-proteolytic activity essential for the structural polyprotein processing and plays a key role in the virus life cycle. CHIKV being an emerging arthropod-borne pathogenic virus, is a public health concern worldwide. No vaccines or specific antiviral treatment is currently available for chikungunya disease. Thus, it is important to develop inhibitors against CHIKV enzymes to block key steps in viral reproduction. In view of this, CVCP was produced recombinantly and purified to homogeneity. A fluorescence resonance energy transfer (FRET)-based proteolytic assay was developed for high throughput screening (HTS). A FRET peptide substrate (DABCYL-GAEEWSLAIE-EDANS) derived from the cleavage site present in the structural polyprotein of CVCP was used. The assay with a Z’ factor of 0.64 and coefficient of variation (CV) is 8.68% can be adapted to high throughput format for automated screening of chemical libraries to identify CVCP specific protease inhibitors. Kinetic parameters K(m) and k(cat)/K(m) estimated using FRET assay were 1.26 ± 0.34 μM and 1.11 × 10(3) M(−1) sec(−1) respectively. The availability of active recombinant CVCP and cost effective fluorogenic peptide based in vitro FRET assay may serve as the basis for therapeutics development against CHIKV.",2015 Oct 6,"['Aggarwal, Megha', 'Sharma, Rajesh', 'Kumar, Pravindra', 'Parida, Manmohan', 'Tomar, Shailly']",Sci Rep,,,True
6f06d1fd7c4ae1397b0a8f5192e9f0c7dc5e62df,PMC,Effect of Porcine Epidemic Diarrhea Virus Infectious Doses on Infection Outcomes in Naïve Conventional Neonatal and Weaned Pigs,http://dx.doi.org/10.1371/journal.pone.0139266,PMC4594914,26441071,CC BY,"Porcine epidemic diarrhea virus (PEDV) was identified in the United States (U.S.) swine population for the first time in April 2013 and rapidly spread nationwide. However, no information has been published regarding the minimum infectious dose (MID) of PEDV in different pig models. The main objective of this study was to determine the oral minimum infectious dose of PEDV in naïve conventional neonatal piglets and weaned pigs. A U.S. virulent PEDV prototype isolate (USA/IN19338/2013) with known infectious titer was serially ten-fold diluted in virus-negative cell culture medium. Dilutions with theoretical infectious titers from 560 to 0.0056 TCID(50)/ml together with a medium control were orogastrically inoculated (10ml/pig) into 7 groups of 5-day-old neonatal pigs (n = 4 per group) and 7 groups of 21-day-old weaned pigs (n = 6 per group). In 5-day-old pigs, 10ml of inoculum having titers 560–0.056 TCID(50)/ml, corresponding to polymerase chain reaction (PCR) cycle threshold (Ct) values 24.2–37.6, resulted in 100% infection in each group; 10ml of inoculum with titer 0.0056 TCID(50)/ml (Ct>45) caused infection in 25% of the inoculated pigs. In 21-day-old pigs, 10ml of inoculum with titers 560–5.6 TCID(50)/ml (Ct 24.2–31.4) resulted in 100% infection in each group while 10ml of inoculum with titers 0.56–0.0056 TCID(50)/ml (Ct values 35.3 –>45) did not establish infection in any pigs under study conditions as determined by clinical signs, PCR, histopathology, immunohistochemistry, and antibody response. These data reveal that PEDV infectious dose is age-dependent with a significantly lower MID for neonatal pigs compared to weaned pigs. This information should be taken into consideration when interpreting clinical relevance of PEDV PCR results and when designing a PEDV bioassay model. The observation of such a low MID in neonates also emphasizes the importance of strict biosecurity and thorough cleaning/disinfection on sow farms.",2015 Oct 6,"['Thomas, Joseph T.', 'Chen, Qi', 'Gauger, Phillip C.', 'Giménez-Lirola, Luis G.', 'Sinha, Avanti', 'Harmon, Karen M.', 'Madson, Darin M.', 'Burrough, Eric R.', 'Magstadt, Drew R.', 'Salzbrenner, Holly M.', 'Welch, Michael W.', 'Yoon, Kyoung-Jin', 'Zimmerman, Jeffrey J.', 'Zhang, Jianqiang']",PLoS One,,,True
6ac46cebdca71f2e25d8a884c5d3ce11fcaf16e7,PMC,Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial,http://dx.doi.org/10.1186/s12931-015-0281-8,PMC4595062,26438038,CC BY,"ABSTRACT: Iota-carrageenan (I-C) is active against respiratory viruses in vitro and was effective as nasal spray in three previous clinical trials. The current trial served to further investigate I-C in patients with early common cold symptoms. METHODS: This randomized, placebo-controlled, double-blind phase IV trial was conducted in 200 adult patients with self-diagnosed colds of <48 h’ duration that were confirmed by baseline cold symptom scores. Patients were to self-administer 0.12 % I-C or placebo spray (NaCl 0.5 %) four times daily for four to ten days and record symptom information for ten days. Common respiratory viruses were quantified by RT-PCR during pretreatment and on Day 3 or 4. The primary endpoint was the mean total symptom score (TSS) of eight cold symptoms on Days 2–4 (TSS(2–4)). RESULTS: Patients in both treatment groups had similar baseline TSSs (mean TSS: 6.75 for I-C and 6.79 for placebo). Viruses were detected in baseline samples from 53 of 98 I-C patients (54.1 %) and 54 of 97 placebo patients (55.7 %). Mean ± SE for TSS(2–4) was 5.78 ± 0.25 for I-C patients and 6.39 ± 0.25 for placebo (p = 0.0895). Exploratory analyses after unblinding (TSS(2–4) excluding a patient with aberrantly high symptom scores [TSS(2–4, ex 1pt)]; mean of TSS over Days 1–4 [TSS(1–4)]; change in TSS(1–4) relative to baseline [TSS(1–4, rel)]) demonstrated treatment differences in favor of I-C (p = 0.0364, p = 0.0495 and p = 0.0421, respectively). For patients with quantifiable rhinovirus/enterovirus at baseline, there was a trend towards greater reduction of virus load at Day 3 or 4 (p = 0.0958; I-C: 90.2 % reduction in viral load; placebo: 72.0 %). Treatments were well tolerated with no differences in adverse event rates. CONCLUSIONS: The primary endpoint did not demonstrate a statistically significant difference between I-C and placebo but showed a trend towards I-C benefit. Exploratory analyses indicated significant reduction of cold symptoms in the I-C group relative to placebo during the first four days when symptoms were most severe, and also substantiated I-C’s activity against rhinovirus/enterovirus. TRIAL REGISTRATION: NCT01944631 (clinicaltrials.gov)",2015 Oct 5,"['Eccles, R.', 'Winther, B.', 'Johnston, S.L.', 'Robinson, P.', 'Trampisch, M.', 'Koelsch, S.']",Respir Res,,,True
e20c3efee1c9653c22821eb34138d6138daefe40,PMC,8(th) International conference on management and rehabilitation of chronic respiratory failure: the long summaries – Part 3,http://dx.doi.org/10.1186/s40248-015-0028-x,PMC4595187,,CC BY,"This paper summarizes the Part 3 of the proceedings of the 8(th) International Conference on Management and Rehabilitation of Chronic Respiratory Failure, held in Pescara, Italy, on 7 and 8 May, 2015. It summarizes the contributions from numerous experts in the field of chronic respiratory disease and chronic respiratory failure. The outline follows the temporal sequence of presentations. This paper (Part 3) presents a section regarding Moving Across the Spectrum of Care for Long-Term Ventilation (Moving Across the Spectrum of Care for Long-Term Ventilation, New Indications for Non-Invasive Ventilation, Elective Ventilation in Respiratory Failure - Can you Prevent ICU Care in Patients with COPD?, Weaning in Long-Term Acute Care Hospitals in the United States, The Difficult-to-Wean Patient: Comprehensive management, Telemonitoring in Ventilator-Dependent Patients, Ethics and Palliative Care in Critically-Ill Respiratory Patients, and Ethics and Palliative Care in Ventilator-Dependent Patients).",2015 Oct 6,"['Ambrosino, Nicolino', 'Casaburi, Richard', 'Chetta, Alfredo', 'Clini, Enrico', 'Donner, Claudio F.', 'Dreher, Michael', 'Goldstein, Roger', 'Jubran, Amal', 'Nici, Linda', 'Owen, Caroline A.', 'Rochester, Carolyn', 'Tobin, Martin J.', 'Vagheggini, Guido', 'Vitacca, Michele', 'ZuWallack, Richard']",Multidiscip Respir Med,,,True
198399348c2c6a7dafb438b3aaba23b43733b105,PMC,Spillover and pandemic properties of zoonotic viruses with high host plasticity,http://dx.doi.org/10.1038/srep14830,PMC4595845,26445169,CC BY,"Most human infectious diseases, especially recently emerging pathogens, originate from animals, and ongoing disease transmission from animals to people presents a significant global health burden. Recognition of the epidemiologic circumstances involved in zoonotic spillover, amplification, and spread of diseases is essential for prioritizing surveillance and predicting future disease emergence risk. We examine the animal hosts and transmission mechanisms involved in spillover of zoonotic viruses to date, and discover that viruses with high host plasticity (i.e. taxonomically and ecologically diverse host range) were more likely to amplify viral spillover by secondary human-to-human transmission and have broader geographic spread. Viruses transmitted to humans during practices that facilitate mixing of diverse animal species had significantly higher host plasticity. Our findings suggest that animal-to-human spillover of new viruses that are capable of infecting diverse host species signal emerging disease events with higher pandemic potential in that these viruses are more likely to amplify by human-to-human transmission with spread on a global scale.",2015 Oct 7,"['Kreuder Johnson, Christine', 'Hitchens, Peta L.', 'Smiley Evans, Tierra', 'Goldstein, Tracey', 'Thomas, Kate', 'Clements, Andrew', 'Joly, Damien O.', 'Wolfe, Nathan D.', 'Daszak, Peter', 'Karesh, William B.', 'Mazet, Jonna K.']",Sci Rep,,,True
d4c687275097c11a1900e5f627c0c28c998e3d65,PMC,Medicinal herb extracts ameliorate impaired growth performance and intestinal lesion of newborn piglets challenged with the virulent porcine epidemic diarrhea virus,http://dx.doi.org/10.1186/s40781-015-0065-1,PMC4597758,26451253,CC BY,"The objective of this study was to evaluate effects of a combined use of extracts of medicinal herbs Taraxaumi mongolicum, Viola yedoensis Makino, Rhizoma coptidis, and Radix isatidis (MYCI) on porcine epidemic diarrhea (PED). Twenty-two 3-day-old piglets received an oral challenge with 3 × 10(3.5) TCID(50) of the virulent PED virus (PEDV) in PBS or PBS only and daily oral administration of 60 mg of the MYCI mixture suspended in milk replacer or the vehicle for 7 days in a 2 × 2 factorial arrangement of treatments. Average daily gain (ADG) increased (p < 0.05) in response to the MYCI treatment in the PEDV-challenged piglets (−18 vs. 7 g for the vehicle- vs. MYCI-administered group), but not in unchallenged animals (27 vs. 28 g). Diarrhea score and fecal PEDV shedding, however, were not influenced by the MYCI treatment. The PEDV challenge caused severe intestinal villus atrophy and crypt hyperplasia, both of which were alleviated by administration of the MYCI mixture as indicated by an increase in the villus height and a decrease in the crypt depth due to the treatment. Overall, medicinal herb extracts used in this study ameliorated impaired growth performance and intestinal lesion of newborn piglets challenged with the virulent PEDV. Therefore, our results suggest that the MYCI mixture could be used as a prophylactic or therapeutic agent against PED.",2015 Oct 8,"['Kim, Hyeun Bum', 'Lee, Chul Young', 'Kim, Sung Jae', 'Han, Jeong Hee', 'Choi, Keum Hwa']",J Anim Sci Technol,,,True
c74616a5ce5f794dde0644f4cb72bf8a196028a3,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,True
ef29dd8567a7f03ed74ad852bc58826ef98c2694,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
b409b662d80651188e2002a79594263364b73828,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
eb51e093b690e76a91250fd21773bfc034eb41e5,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
1a9668b9c7aeac67694959bcb34c570ab08eebf7,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
a4a438543c6177f81f10993e2b2d3d211642297e,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
0c2ffc7e9950254f236cf4d27f80ea1fadef516f,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
659f4b4eb3c2f8c437a86957f76d166708610d6a,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
c11a9e64e19e76eb7aab68a755341d9d42073d8d,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
13d22e11924648d3aae4f0acc34127c2f9194ef4,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
17eaf34d4dba0463e7957994ff5ab3d7ba2041d4,PMC,"Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses",http://dx.doi.org/10.1371/journal.ppat.1005173,PMC4598190,26448646,CC BY,"Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.",2015 Oct 8,"['Paquette, Stéphane G.', 'Banner, David', 'Huang, Stephen S. H.', 'Almansa, Raquel', 'Leon, Alberto', 'Xu, Luoling', 'Bartoszko, Jessica', 'Kelvin, David J.', 'Kelvin, Alyson A.']",PLoS Pathog,,,False
3bfdf7dff1f50821c7fd782b0c6c0b4d56bf1815,PMC,Promoting public health legal preparedness for emergencies: review of current trends and their relevance in light of the Ebola crisis,http://dx.doi.org/10.3402/gha.v8.28871,PMC4598337,26449204,CC BY,"BACKGROUND: Public health legal preparedness (PHLP) for emergencies is a core component of the health system response. However, the implementation of health legal preparedness differs between low- and middle-income countries (LMIC) and developed countries. OBJECTIVE: This paper examines recent trends regarding public health legal preparedness for emergencies and discusses its role in the recent Ebola outbreak. DESIGN: A rigorous literature review was conducted using eight electronic databases as well as Google Scholar. The results encompassed peer-reviewed English articles, reports, theses, and position papers dating from 2011 to 2014. Earlier articles concerning regulatory actions were also examined. RESULTS: The importance of PHLP has grown during the past decade and focuses mainly on infection–disease scenarios. Amid LMICs, it mostly refers to application of international regulations, whereas in developed states, it focuses on independent legislation and creation of conditions optimal to promoting an effective emergency management. Among developed countries, the United States’ utilisation of health legal preparedness is the most advanced, including the creation of a model comprising four elements: law, competencies, information, and coordination. Only limited research has been conducted in this field to date. Nevertheless, in both developed and developing states, studies that focused on regulations and laws activated in health systems during emergencies, identified inconsistency and incoherence. The Ebola outbreak plaguing West Africa since 2014 has global implications, challenges and paralleling results, that were identified in this review. CONCLUSIONS: The review has shown the need to broaden international regulations, to deepen reciprocity between countries, and to consider LMICs health capacities, in order to strengthen the national health security. Adopting elements of the health legal preparedness model is recommended.",2015 Oct 7,"['Cohen, Odeya', 'Feder-Bubis, Paula', 'Bar-Dayan, Yaron', 'Adini, Bruria']",Glob Health Action,,,True
edea2cda674c33bb251b64e5416f5380f13d5489,PMC,Genome Wide Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross,http://dx.doi.org/10.1371/journal.pgen.1005504,PMC4599853,26452100,CC0,"New systems genetics approaches are needed to rapidly identify host genes and genetic networks that regulate complex disease outcomes. Using genetically diverse animals from incipient lines of the Collaborative Cross mouse panel, we demonstrate a greatly expanded range of phenotypes relative to classical mouse models of SARS-CoV infection including lung pathology, weight loss and viral titer. Genetic mapping revealed several loci contributing to differential disease responses, including an 8.5Mb locus associated with vascular cuffing on chromosome 3 that contained 23 genes and 13 noncoding RNAs. Integrating phenotypic and genetic data narrowed this region to a single gene, Trim55, an E3 ubiquitin ligase with a role in muscle fiber maintenance. Lung pathology and transcriptomic data from mice genetically deficient in Trim55 were used to validate its role in SARS-CoV-induced vascular cuffing and inflammation. These data establish the Collaborative Cross platform as a powerful genetic resource for uncovering genetic contributions of complex traits in microbial disease severity, inflammation and virus replication in models of outbred populations.",2015 Oct 9,"['Gralinski, Lisa E.', 'Ferris, Martin T.', 'Aylor, David L.', 'Whitmore, Alan C.', 'Green, Richard', 'Frieman, Matthew B.', 'Deming, Damon', 'Menachery, Vineet D.', 'Miller, Darla R.', 'Buus, Ryan J.', 'Bell, Timothy A.', 'Churchill, Gary A.', 'Threadgill, David W.', 'Katze, Michael G.', 'McMillan, Leonard', 'Valdar, William', 'Heise, Mark T.', 'Pardo-Manuel de Villena, Fernando', 'Baric, Ralph S.']",PLoS Genet,,,True
fe2ad749589ac1371ec020700775e8de3c809f41,PMC,The early immune response to infection of chickens with Infectious Bronchitis Virus (IBV) in susceptible and resistant birds,http://dx.doi.org/10.1186/s12917-015-0575-6,PMC4600211,26452558,CC BY,"BACKGROUND: Infectious Bronchitis is a highly contagious respiratory disease which causes tracheal lesions and also affects the reproductive tract and is responsible for large economic losses to the poultry industry every year. This is due to both mortality (either directly provoked by IBV itself or due to subsequent bacterial infection) and lost egg production. The virus is difficult to control by vaccination, so new methods to curb the impact of the disease need to be sought. Here, we seek to identify genes conferring resistance to this coronavirus, which could help in selective breeding programs to rear chickens which do not succumb to the effects of this disease. METHODS: Whole genome gene expression microarrays were used to analyse the gene expression differences, which occur upon infection of birds with Infectious Bronchitis Virus (IBV). Tracheal tissue was examined from control and infected birds at 2, 3 and 4 days post-infection in birds known to be either susceptible or resistant to the virus. The host innate immune response was evaluated over these 3 days and differences between the susceptible and resistant lines examined. RESULTS: Genes and biological pathways involved in the early host response to IBV infection were determined andgene expression differences between susceptible and resistant birds were identified. Potential candidate genes for resistance to IBV are highlighted. CONCLUSIONS: The early host response to IBV is analysed and potential candidate genes for disease resistance are identified. These putative resistance genes can be used as targets for future genetic and functional studies to prove a causative link with resistance to IBV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0575-6) contains supplementary material, which is available to authorized users.",2015 Oct 9,"['Smith, Jacqueline', 'Sadeyen, Jean-Remy', 'Cavanagh, David', 'Kaiser, Pete', 'Burt, David W.']",BMC Vet Res,,,False
4d1f8955a62f01fe7a4d7d19593bdbd6047f4f41,PMC,The early immune response to infection of chickens with Infectious Bronchitis Virus (IBV) in susceptible and resistant birds,http://dx.doi.org/10.1186/s12917-015-0575-6,PMC4600211,26452558,CC BY,"BACKGROUND: Infectious Bronchitis is a highly contagious respiratory disease which causes tracheal lesions and also affects the reproductive tract and is responsible for large economic losses to the poultry industry every year. This is due to both mortality (either directly provoked by IBV itself or due to subsequent bacterial infection) and lost egg production. The virus is difficult to control by vaccination, so new methods to curb the impact of the disease need to be sought. Here, we seek to identify genes conferring resistance to this coronavirus, which could help in selective breeding programs to rear chickens which do not succumb to the effects of this disease. METHODS: Whole genome gene expression microarrays were used to analyse the gene expression differences, which occur upon infection of birds with Infectious Bronchitis Virus (IBV). Tracheal tissue was examined from control and infected birds at 2, 3 and 4 days post-infection in birds known to be either susceptible or resistant to the virus. The host innate immune response was evaluated over these 3 days and differences between the susceptible and resistant lines examined. RESULTS: Genes and biological pathways involved in the early host response to IBV infection were determined andgene expression differences between susceptible and resistant birds were identified. Potential candidate genes for resistance to IBV are highlighted. CONCLUSIONS: The early host response to IBV is analysed and potential candidate genes for disease resistance are identified. These putative resistance genes can be used as targets for future genetic and functional studies to prove a causative link with resistance to IBV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0575-6) contains supplementary material, which is available to authorized users.",2015 Oct 9,"['Smith, Jacqueline', 'Sadeyen, Jean-Remy', 'Cavanagh, David', 'Kaiser, Pete', 'Burt, David W.']",BMC Vet Res,,,True
eb018f450fa6903ccf3c0c151b24a814ee81fd55,PMC,Ring finger protein 166 potentiates RNA virus-induced interferon-β production via enhancing the ubiquitination of TRAF3 and TRAF6,http://dx.doi.org/10.1038/srep14770,PMC4600972,26456228,CC BY,"Host cells orchestrate the production of IFN-β upon detecting invading viral pathogens. Here, we report that Ring finger protein 166 (RNF166) potentiates RNA virus-triggered IFN-β production. Overexpression of RNF166 rather than its homologous proteins RNF114, RNF125, and RNF138, enhanced Sendai virus (SeV)-induced activation of the IFN-β promoter. Knockdown of endogenous RNF166, but not other RNFs, inhibited the IFN-β production induced by SeV and encephalomyocarditis virus. RNF166 interacted with TRAF3 and TRAF6. SeV-induced ubiquitination of TRAF3 and TRAF6 was suppressed when endogenous RNF166 rather than RNF114/138 was knocked down. These findings suggest that RNF166 positively regulates RNA virus-triggered IFN-β production by enhancing the ubiquitination of TRAF3 and TRAF6.",2015 Oct 12,"['Chen, Hai-Wei', 'Yang, Yong-Kang', 'Xu, Hao', 'Yang, Wei-Wei', 'Zhai, Zhong-He', 'Chen, Dan-Ying']",Sci Rep,,,True
cada5ab8069fa39139ce27d9568654e67993adbf,PMC,Positron Emission Tomography With (18)F-Fluorodeoxyglucose in Patients With Sickle Cell Acute Chest Syndrome,http://dx.doi.org/10.1097/MD.0000000000000821,PMC4602525,25950690,CC BY,"The acute chest syndrome (ACS) is the main cause of mortality among adult patients with sickle cell disease (SCD). Its pathophysiology is still unclear. Using positron emission tomography (PET) with (18)F-fluorodeoxyglucose [18F-fluorodeoxyglucose ((18)F-FDG)], we explored the relationship between regional lung density and lung metabolism, as a reflection of lung neutrophilic infiltration during ACS. Patients were prospectively enrolled in a single-center study. Dual modality chest PET/computed tomography (CT) scans were performed, with (18)F-FDG emission scans for quantification of regional (18)F-FDG uptake and CT scans with radiocontrast agent to check for pulmonary artery thrombosis. Regional lung (18)F-FDG uptake was quantified in ACS patients and in SCD patients without ACS (SCD non-ACS controls). Maximal (SUVmax) and mean (SUVmean) standardized uptake values were computed. Seventeen patients with ACS (mean age 28.3 ± 6.4 years) were included. None died nor required invasive mechanical ventilation. The main lung opacity on CT scans was lower lobe consolidation. Lungs of patients with ACS exhibited higher SUVmax than those of SCD non-ACS controls (2.5 [2.1–2.9] vs 0.8 [0.6–1.0]; P < 0.0001). Regional SUVmax and SUVmean was higher in lower than in upper lobes of ACS patients (P < 0.001) with a significant correlation between lung density and SUVmax (R(2) = 0.78). SUVmean was higher in upper lobes of ACS patients than in lungs of SCD non-ACS controls (P < 0.001). Patients with SUVmax >2.5 had longer intensive care unit (ICU) stay than others (7 [6–11] vs 4 [3–6] days; P = 0.016). Lungs of patients with ACS exhibited higher (18)F-FDG uptake than SCD non-ACS controls. Lung apices had normal aeration and lower (18)F-FDG uptake than lung bases, but higher (18)F-FDG uptake than lungs of SCD non-ACS controls. Patients with higher lung (18)F-FDG uptake had longer ICU stay than others.",2015 May 8,"['de Prost, Nicolas', 'Sasanelli, Myriam', 'Deux, Jean-François', 'Habibi, Anoosha', 'Razazi, Keyvan', 'Galactéros, Frédéric', 'Meignan, Michel', 'Maître, Bernard', 'Brun-Buisson, Christian', 'Itti, Emmanuel', 'Dessap, Armand Mekontso']",Medicine (Baltimore),,,True
982210556d79705b5b48d86ca09aadf517bd0edb,PMC,No Direct Association Between Asthma and the Microbiome Based on Currently Available Techniques,http://dx.doi.org/10.1097/MD.0000000000000199,PMC4602810,25501073,CC BY,"Current uses of culture-independent tools in previous studies have shown a significant relationship between microbiota and asthma. Although these studies are relatively new, there is also evidence of the possibility of new therapeutic strategies for the treatment or prevention of asthma. This article retrospectively examines the possible association between microorganisms and asthma. Data on all patients with different types of asthma were collected from hospital charts from the Department of Internal Medicine, Saarland University Medical Center, Germany, within the study period of 2011 to 2012. The tracheal secretions of asthmatics obtained by bronchoalveolar lavage, bronchial aspirates through flexible bronchoscopy, and directly in sputum were examined microbiologically for microorganisms. Thirty-one (10.47%, 95% CI, 6.98–13.96) of a total of 296 patients were found to have asthma microorganisms in their airways. We could not establish a causal relationship between microorganisms and asthma based on the results of our study (P = 0.893). Additionally, acute respiratory infections did not affect the microbiological colonization in asthmatics’ airways (P = 0.472). We were unable to find a direct association between asthma and the microbiome based on existing diagnostic techniques.",2014 Dec 12,"Yayan, Josef",Medicine (Baltimore),,,True
00142f93c18b07350be89e96372d240372437ed9,PMC,Immunity to Pathogens Taught by Specialized Human Dendritic Cell Subsets,http://dx.doi.org/10.3389/fimmu.2015.00527,PMC4603245,26528289,CC BY,"Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) that have a key role in immune responses because they bridge the innate and adaptive arms of the immune system. They mature upon recognition of pathogens and upregulate MHC molecules and costimulatory receptors to activate antigen-specific CD4(+) and CD8(+) T cells. It is now well established that DCs are not a homogeneous population but are composed of different subsets with specialized functions in immune responses to specific pathogens. Upon viral infections, plasmacytoid DCs (pDCs) rapidly produce large amounts of IFN-α, which has potent antiviral functions and activates several other immune cells. However, pDCs are not particularly potent APCs and induce the tolerogenic cytokine IL-10 in CD4(+) T cells. In contrast, myeloid DCs (mDCs) are very potent APCs and possess the unique capacity to prime naive T cells and consequently to initiate a primary adaptive immune response. Different subsets of mDCs with specialized functions have been identified. In mice, CD8α(+) mDCs capture antigenic material from necrotic cells, secrete high levels of IL-12, and prime Th1 and cytotoxic T-cell responses to control intracellular pathogens. Conversely, CD8α(−) mDCs preferentially prime CD4(+) T cells and promote Th2 or Th17 differentiation. BDCA-3(+) mDC2 are the human homologue of CD8α(+) mDCs, since they share the expression of several key molecules, the capacity to cross-present antigens to CD8(+) T-cells and to produce IFN-λ. However, although several features of the DC network are conserved between humans and mice, the expression of several toll-like receptors as well as the production of cytokines that regulate T-cell differentiation are different. Intriguingly, recent data suggest specific roles for human DC subsets in immune responses against individual pathogens. The biology of human DC subsets holds the promise to be exploitable in translational medicine, in particular for the development of vaccines against persistent infections or cancer.",2015 Oct 13,"['Geginat, Jens', 'Nizzoli, Giulia', 'Paroni, Moira', 'Maglie, Stefano', 'Larghi, Paola', 'Pascolo, Steve', 'Abrignani, Sergio']",Front Immunol,,,True
72b1311ad0c502a391201bff5805dcc57ee1c9e1,PMC,The Hepatitis E virus intraviral interactome,http://dx.doi.org/10.1038/srep13872,PMC4604457,26463011,CC BY,"Hepatitis E virus (HEV) is an emerging virus causing epidemic acute hepatitis in developing countries as well as sporadic cases in industrialized countries. The life cycle of HEV is still poorly understood and the lack of efficient cell culture systems and animal models are the principal limitations for a detailed study of the viral replication cycle. Here we exhaustively examine all possible intraviral protein-protein interactions (PPIs) of HEV by systematic Yeast two-hybrid (Y2H) and LuMPIS screens, providing a basis for studying the function of these proteins in the viral replication cycle. Key PPIs correlate with the already published HEV 3D structure. Furthermore, we report 20 novel PPIs including the homodimerization of the RNA dependent RNA polymerase (RdRp), the self-interaction of the papain like protease, and ORF3 interactions with the papain-like protease and putative replicase components: RdRp, methylase and helicase. Furthermore, we determined the dissociation constant (K(d)) of ORF3 interactions with the viral helicase, papain-like protease and methylase, which suggest a regulatory function for ORF3 in orchestrating the formation of the replicase complex. These interactions may represent new targets for antiviral drugs.",2015 Oct 14,"['Osterman, Andreas', 'Stellberger, Thorsten', 'Gebhardt, Anna', 'Kurz, Marisa', 'Friedel, Caroline C.', 'Uetz, Peter', 'Nitschko, Hans', 'Baiker, Armin', 'Vizoso-Pinto, Maria G.']",Sci Rep,,,True
865165018fb3cac831bd7f134dc240d038c25b0c,PMC,The Hepatitis E virus intraviral interactome,http://dx.doi.org/10.1038/srep13872,PMC4604457,26463011,CC BY,"Hepatitis E virus (HEV) is an emerging virus causing epidemic acute hepatitis in developing countries as well as sporadic cases in industrialized countries. The life cycle of HEV is still poorly understood and the lack of efficient cell culture systems and animal models are the principal limitations for a detailed study of the viral replication cycle. Here we exhaustively examine all possible intraviral protein-protein interactions (PPIs) of HEV by systematic Yeast two-hybrid (Y2H) and LuMPIS screens, providing a basis for studying the function of these proteins in the viral replication cycle. Key PPIs correlate with the already published HEV 3D structure. Furthermore, we report 20 novel PPIs including the homodimerization of the RNA dependent RNA polymerase (RdRp), the self-interaction of the papain like protease, and ORF3 interactions with the papain-like protease and putative replicase components: RdRp, methylase and helicase. Furthermore, we determined the dissociation constant (K(d)) of ORF3 interactions with the viral helicase, papain-like protease and methylase, which suggest a regulatory function for ORF3 in orchestrating the formation of the replicase complex. These interactions may represent new targets for antiviral drugs.",2015 Oct 14,"['Osterman, Andreas', 'Stellberger, Thorsten', 'Gebhardt, Anna', 'Kurz, Marisa', 'Friedel, Caroline C.', 'Uetz, Peter', 'Nitschko, Hans', 'Baiker, Armin', 'Vizoso-Pinto, Maria G.']",Sci Rep,,,False
04be45dba1c24d640d5da8298c5f01e3165d84c4,PMC,Association between Use of Oral Anti-Diabetic Drugs and the Risk of Sepsis: A Nested Case-Control Study,http://dx.doi.org/10.1038/srep15260,PMC4604480,26463557,CC BY,"Although oral antidiabetic drugs (OADs) have been associated with immunomodulation in preclinical studies, little is still known about the association between the use of OADs and the risk of sepsis. Using a cohort of patients, extracted from Taiwan’s National Health Insurance Research Database, with type 2 diabetes who were newly diagnosed between 2010 and 2012 and treated with OADs, we conducted a nested case-control study involving 43,015 cases (patients who were first hospitalized for sepsis) and 43,015 matched controls. Compared with non-use, metformin use was associated with a decreased risk of developing sepsis (adjusted odds ratio [OR] 0.80, 95% confidence interval [CI] 0.77–0.83, P < 0.001), but meglitinide (adjusted OR 1.32, 95% CI 1.25–1.40, P < 0.001) use was associated with the increased risk of developing sepsis. The risk for development of sepsis was also lower among current (adjusted OR 0.87, 95% CI 0.78–0.96) and recent (adjusted OR 0.83, 95% CI 0.73–0.94) thiazolidinedione users. Current or recent sulfonylurea use and dipeptidyl peptidase-4 inhibitor use were not significantly associated with the development of sepsis. Our results highlight the need to consider the potential pleiotropic effect of OADs against sepsis in addition to the lowering of blood glucose.",2015 Oct 14,"['Shih, Chia-Jen', 'Wu, Yueh-Lin', 'Chao, Pei-Wen', 'Kuo, Shu-Chen', 'Yang, Chih-Yu', 'Li, Szu-Yuan', 'Ou, Shuo-Ming', 'Chen, Yung-Tai']",Sci Rep,,,True
814ec1dc13c5f446a41d1b3f1becb6495897455a,PMC,"Human polyomavirus type six in respiratory samples from hospitalized children with respiratory tract infections in Beijing, China",http://dx.doi.org/10.1186/s12985-015-0390-5,PMC4604616,26463646,CC BY,"BACKGROUND: HPyV6 is a novel human polyomavirus (HPyV), and neither its natural history nor its prevalence in human disease is well known. Therefore, the epidemiology and phylogenetic status of HPyV6 must be systematically characterized. METHODS: The VP1 gene of HPyV6 was detected with an established TaqMan real-time PCR from nasopharyngeal aspirate specimens collected from hospitalized children with respiratory tract infections. The HPyV6-positive specimens were screened for other common respiratory viruses with real-time PCR assays. RESULTS: The prevalence of HPyV6 was 1.7 % (15/887), and children ≤ 5 years of age accounted for 80 % (12/15) of cases. All 15 HPyV6-positive patients were coinfected with other respiratory viruses, of which influenza virus A (IFVA) (8/15, 53.3 %) and respiratory syncytial virus (7/15, 46.7 %) were most common. All 15 HPyV6-positive patients were diagnosed with lower respiratory tract infections, and their viral loads ranged from 1.38 to 182.42 copies/μl nasopharyngeal aspirate specimen. The most common symptoms were cough (100 %) and fever (86.7 %). The complete 4926-bp genome (BJ376 strain, GenBank accession number KM387421) was amplified and showed 100 % identity to HPyV6 strain 607a. CONCLUSIONS: The prevalence of HPyV6 was 1.7 % in nasopharyngeal aspirate specimens from hospitalized children with respiratory tract infections, as analyzed by real-time PCR. Because the coinfection rate was high and the viral load low, it was not possible to establish a correlation between HPyV6 and respiratory diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0390-5) contains supplementary material, which is available to authorized users.",2015 Oct 13,"['Zheng, Wen-zhi', 'Wei, Tian-li', 'Ma, Fen-lian', 'Yuan, Wu-mei', 'Zhang, Qian', 'Zhang, Ya-xin', 'Cui, Hong', 'Zheng, Li-shu']",Virol J,,,True
d1a76cbc915984f693d508e9024c67d001aa20d6,PMC,Review of economic evaluations of mask and respirator use for protection against respiratory infection transmission,http://dx.doi.org/10.1186/s12879-015-1167-6,PMC4605092,26462473,CC BY,"BACKGROUND: There has been increasing debate surrounding mask and respirator interventions to control respiratory infection transmission in both healthcare and community settings. As decision makers are considering the recommendations they should evaluate how to provide the most efficient protection strategies with minimum costs. The aim of this review is to identify and evaluate the existing economic evaluation literature in this area and to offer advice on how future evaluations on this topic should be conducted. METHODS: We searched the Scopus database for all literature on economic evaluation of mask or respirator use to control respiratory infection transmission. Reference lists from the identified studies were also manually searched. Seven studies met our inclusion criteria from the initial 806 studies identified by the search strategy and our manual search. RESULTS: Five studies considered interventions for seasonal and/or pandemic influenza, with one also considering SARS (Severe Acute Respiratory Syndrome). The other two studies focussed on tuberculosis transmission control interventions. The settings and methodologies of the studies varied greatly. No low-middle income settings were identified. Only one of the reviewed studies cited clinical evidence to inform their mask/respirator intervention effectiveness parameters. Mask and respirator interventions were generally reported by the study authors to be cost saving or cost-effective when compared to no intervention or other control measures, however the evaluations had important limitations. CONCLUSIONS: Given the large cost differential between masks and respirators, there is a need for more comprehensive economic evaluations to compare the relative costs and benefits of these interventions in situations and settings where alternative options are potentially applicable. There are at present insufficient well conducted cost-effectiveness studies to inform decision-makers on the value for money of alternative mask/respirator options.",2015 Oct 13,"['Mukerji, Shohini', 'MacIntyre, C. Raina', 'Newall, Anthony T.']",BMC Infect Dis,,,True
468cd07dc546d39f95529846f303e76f02ae51b3,PMC,Nucleolin stabilizes G-quadruplex structures folded by the LTR promoter and silences HIV-1 viral transcription,http://dx.doi.org/10.1093/nar/gkv897,PMC4605322,26354862,CC BY,"Folding of the LTR promoter into dynamic G-quadruplex conformations has been shown to suppress its transcriptional activity in HIV-1. Here we sought to identify the proteins that control the folding of this region of proviral genome by inducing/stabilizing G-quadruplex structures. The implementation of electrophorethic mobility shift assay and pull-down experiments coupled with mass spectrometric analysis revealed that the cellular protein nucleolin is able to specifically recognize G-quadruplex structures present in the LTR promoter. Nucleolin recognized with high affinity and specificity the majority, but not all the possible G-quadruplexes folded by this sequence. In addition, it displayed greater binding preference towards DNA than RNA G-quadruplexes, thus indicating two levels of selectivity based on the sequence and nature of the target. The interaction translated into stabilization of the LTR G-quadruplexes and increased promoter silencing activity; in contrast, disruption of nucleolin binding in cells by both siRNAs and a nucleolin binding aptamer greatly increased LTR promoter activity. These data indicate that nucleolin possesses a specific and regulated activity toward the HIV-1 LTR promoter, which is mediated by G-quadruplexes. These observations provide new essential insights into viral transcription and a possible low mutagenic target for antiretroviral therapy.",2015 Oct 15,"['Tosoni, Elena', 'Frasson, Ilaria', 'Scalabrin, Matteo', 'Perrone, Rosalba', 'Butovskaya, Elena', 'Nadai, Matteo', 'Palù, Giorgio', 'Fabris, Dan', 'Richter, Sara N.']",Nucleic Acids Res,,,True
912c5e77617283256e75b99546edc81e13af0ef6,PMC,Nucleolin stabilizes G-quadruplex structures folded by the LTR promoter and silences HIV-1 viral transcription,http://dx.doi.org/10.1093/nar/gkv897,PMC4605322,26354862,CC BY,"Folding of the LTR promoter into dynamic G-quadruplex conformations has been shown to suppress its transcriptional activity in HIV-1. Here we sought to identify the proteins that control the folding of this region of proviral genome by inducing/stabilizing G-quadruplex structures. The implementation of electrophorethic mobility shift assay and pull-down experiments coupled with mass spectrometric analysis revealed that the cellular protein nucleolin is able to specifically recognize G-quadruplex structures present in the LTR promoter. Nucleolin recognized with high affinity and specificity the majority, but not all the possible G-quadruplexes folded by this sequence. In addition, it displayed greater binding preference towards DNA than RNA G-quadruplexes, thus indicating two levels of selectivity based on the sequence and nature of the target. The interaction translated into stabilization of the LTR G-quadruplexes and increased promoter silencing activity; in contrast, disruption of nucleolin binding in cells by both siRNAs and a nucleolin binding aptamer greatly increased LTR promoter activity. These data indicate that nucleolin possesses a specific and regulated activity toward the HIV-1 LTR promoter, which is mediated by G-quadruplexes. These observations provide new essential insights into viral transcription and a possible low mutagenic target for antiretroviral therapy.",2015 Oct 15,"['Tosoni, Elena', 'Frasson, Ilaria', 'Scalabrin, Matteo', 'Perrone, Rosalba', 'Butovskaya, Elena', 'Nadai, Matteo', 'Palù, Giorgio', 'Fabris, Dan', 'Richter, Sara N.']",Nucleic Acids Res,,,False
425be277181521bab21a8e64d54657dfdcac6bde,PMC,Detection and characterization of respiratory viruses causing acute respiratory illness and asthma exacerbation in children during three different seasons (2011–2014) in Mexico City,http://dx.doi.org/10.1111/irv.12346,PMC4605408,26289993,CC BY,"BACKGROUND: Viral infections play a significant role in causing acute respiratory infections (ARIs) and exacerbations of chronic diseases. Acute respiratory infections are now the leading cause of mortality in children worldwide, especially in developing countries. Recently, human rhinovirus (HRV) infection has been emerged as an important cause of pneumonia and asthma exacerbation. OBJECTIVES: To determine the role of several viral agents principally, respiratory syncytial virus, and HRV in children with ARIs and their relationship with asthma exacerbation and pneumonia. METHODS: Between October 2011 and March 2014, 432 nasopharyngeal samples of children <15 years of age with ARI hospitalized at a referral hospital for respiratory diseases were tested for the presence of respiratory viruses using a multiplex RT-qPCR. Clinical, epidemiological, and demographic data were collected and associated with symptomatology and viral infections. RESULTS: Viral infections were detected in at least 59·7% of the enrolled patients, with HRV (26·6%) being the most frequently detected. HRV infections were associated with clinical features of asthma and difficulty in breathing such as wheezing (P = 0·0003), supraesternal (P = 0·046), and xiphoid retraction (P = 0·030). HRV subtype C (HRV-C) infections were associated with asthma (P = 0·02). CONCLUSIONS: Human rhinovirus was the virus most commonly detected in pediatric patients with ARI. There is also an association of HRV-C infection with asthma exacerbation, emphasizing the relevance of this virus in severe pediatric respiratory disease.",2015 Nov 13,"['Moreno-Valencia, Yazmin', 'Hernandez-Hernandez, Victor A', 'Romero-Espinoza, Jose A I', 'Coronel-Tellez, Rodrigo H', 'Castillejos-Lopez, Manuel', 'Hernandez, Andres', 'Perez-Padilla, Rogelio', 'Alejandre-Garcia, Alejandro', 'de la Rosa-Zamboni, Daniela', 'Ormsby, Christopher E', 'Vazquez-Perez, Joel A']",Influenza Other Respir Viruses,,,True
bd921a71bee40ea8cb9c3725c6dce6ad0ce5a560,PMC,"Prevalence of human parainfluenza virus in patients with acute respiratory tract infections in Beijing, 2011–2014",http://dx.doi.org/10.1111/irv.12336,PMC4605411,26230490,CC BY,,2015 Nov 13,"['Shi, Weixian', 'Cui, Shujuan', 'Gong, Cheng', 'Zhang, Tiegang', 'Yu, Xiali', 'Li, Aihua', 'Chen, Meng', 'Luo, Ming', 'Huang, Fang']",Influenza Other Respir Viruses,,,True
86c378531ecb4b4d351c844fc4e3e5c9cf49f269,PMC,Elevated transmission of upper respiratory illness among new recruits in military barracks in Thailand,http://dx.doi.org/10.1111/irv.12345,PMC4605412,26271648,CC BY,"BACKGROUND: New recruits within military barracks present conditions favorable for the spread of respiratory pathogens. However, respiratory pathogen transmission in such confined settings in the tropics has not been well studied. METHODS: Recruits in four successive Royal Thai Army basic training classes living in military barracks were monitored for the symptoms of influenza-like illness (ILI) or upper respiratory illness (URI). Classes 1 and 2 were also monitored after basic training. Nasal/throat swabs from acute illnesses were collected and tested by influenza RT-PCR (all four classes). In addition, class 1 had multiplex PCR performed along with the analysis of bed locations within the barracks. RESULTS: Influenza-like illness/upper respiratory illness rates ranged from 4·7 to 6·9 per 100 recruit-weeks in the four classes and generally decreased during the course of basic training (P < 0·05 in three of four classes). Rates during basic training were 1·7 (95% CI: 1·29, 2·29) and 2·5 (95% CI: 1·5, 4·1) times higher than after basic training (classes 1 and 2, respectively). In class 1, coronavirus, parainfluenza virus, and rhinovirus were the most commonly identified respiratory pathogens; only one influenza PCR-positive infection was detected in all four classes. Bed locations of URI/ILI cases in class 1 tended to be in closer proximity to each other. CONCLUSION: Basic training recruits in military barracks in the tropics had high rates of acute respiratory illnesses with illness patterns consistent with external seeding followed by substantial internal transmission. Our findings may contribute to control measures in similar confined settings both within and outside the military.",2015 Nov 13,"['Levy, Jens W', 'Bhoomiboonchoo, Piraya', 'Simasathien, Sriluck', 'Salje, Henrik', 'Huang, Angkana', 'Rangsin, Ram', 'Jarman, Richard G', 'Fernandez, Stefan', 'Klungthong, Chonticha', 'Hussem, Kittinun', 'Gibbons, Robert V', 'Yoon, In-Kyu']",Influenza Other Respir Viruses,,,True
a8f484e668a71d016a40b1fd1de16fbf2e539ebe,PMC,"Viral and atypical bacterial aetiologies of infection in hospitalised patients admitted with clinical suspicion of influenza in Thailand, Vietnam and Indonesia",http://dx.doi.org/10.1111/irv.12326,PMC4605413,25980749,CC BY,"BACKGROUND: Influenza constitutes a leading cause of morbidity and mortality worldwide. There is limited information about the aetiology of infection presenting clinically as influenza in hospitalised adults and children in South-East Asia. Such data are important for future management of respiratory infections. OBJECTIVES: To describe the aetiology of infection presenting clinically as influenza in those hospitalised in South-East Asia. METHODS: Respiratory specimens archived from July 2008 to June 2009 from patients hospitalised with suspected influenza from Indonesia, Thailand and Vietnam were tested for respiratory viruses and atypical bacteria by polymerase chain reaction. RESULTS: A total of 1222 patients’ samples were tested. Of 1222, 776 patients (63·5%) were under the age of 5. Viruses detected included rhinoviruses in 229 of 1222 patients (18·7%), bocaviruses in 200 (16·4%), respiratory syncytial viruses in 144 (11·8%), parainfluenza viruses in 140 (11·5%; PIV1: 32; PIV2: 12; PIV3: 71; PIV4: 25), adenovirus in 102 (8·4%), influenza viruses in 93 (7·6%; influenza A: 77; influenza B: 16) and coronaviruses in 23 (1·8%; OC43: 14; E229: 9). Bacterial pathogens were Mycoplasma pneumoniae (n = 33, 2·7%), Chlamydophila psittaci (n = 2), C. pneumoniae (n = 1), Bordetella pertussis (n = 1) and Legionella pneumophila (n = 2). Overall, in-hospital case fatality rate was 29 of 1222 (2·4%). CONCLUSION: Respiratory viruses were the most commonly detected pathogens in patients hospitalised with a clinical suspicion of influenza. Rhinovirus was the most frequently detected virus, and M. pneumoniae, the most common atypical bacterium. The low number of detected influenza viruses demonstrates a low benefit for empirical oseltamivir therapy, unless during an influenza outbreak.",2015 Nov 13,"['Wertheim, Heiman F L', 'Nadjm, Behzad', 'Thomas, Sherine', 'Malik, Suhud', 'Nguyen, Diep Ngoc Thi', 'Vu, Dung Viet Tien', 'Van Nguyen, Kinh', 'Van Nguyen, Chau Vinh', 'Nguyen, Liem Thanh', 'Tran, Sinh Thi', 'Phung, Thuy Bich Thi', 'Nguyen, Trung Vu', 'Hien, Tran Tinh', 'Nguyen, Uyen Hanh', 'Taylor, Walter', 'Truong, Khanh Huu', 'Ha, Tuan Manh', 'Chokephaibulkit, Kulkanya', 'Farrar, Jeremy', 'Wolbers, Marcel', 'de Jong, Menno D', 'van Doorn, H Rogier', 'Puthavathana, Pilaipan']",Influenza Other Respir Viruses,,,True
0d1ca8ed239b0d50c0dc8a21041a1a1c43045806,PMC,Challenges of the Pandemic Response in Primary Care during Pre-Vaccination Period: A Qualitative Study,http://dx.doi.org/10.1186/s13584-015-0028-5,PMC4606524,26473026,CC BY,"BACKGROUND: During the 2009/A/H1N1 pandemic, the main burden of the patient management fell on primary care physicians (PCPs), and they were the principal implementers of pandemic policies. Broad involvement of PCPs in the pandemic response offered an excellent opportunity to investigate the challenges that they encountered. OBJECTIVE: To examine challenges faced by PCPs as they implemented pandemic policies in Australia, Israel and England before the 2009/A/H1N1 pandemic vaccine became available. METHODS: This is a qualitative descriptive study that employed in-depth semi-structured interviews with 65 PCPs from Australia, Israel and England. The data were analysed thematically to provide a detailed account of the themes. RESULTS: Challenges in three fields of the pandemic response were identified. (i) Consultation of patients was challenged by the high flow of patients, sick and worried-well, the necessity to provide personalised information about the disease during consultations, and unfamiliar antiviral treatment. (ii) Performance of public health responsibilities was complicated in regards to patient segregation and introduction of personal protection measures. (iii) Communication with the health authorities was inefficient, with no established route to provide feedback about the pandemic policies. CONCLUSIONS: The experience of the 2009/A/H1N1 pandemic highlighted the centrality of primary care in the pandemic response. Despite intensive pre-pandemic planning, numerous barriers for implementation of the pandemic policies in primary care were identified. Investigation of three different approaches for involvement of PCPs in the pandemic management showed that none of these approaches worked smoothly.",2015 Oct 15,"['Kunin, Marina', 'Engelhard, Dan', 'Thomas, Shane', 'Ashworth, Mark', 'Piterman, Leon']",Isr J Health Policy Res,,,True
355eb5b5bf565e8e432d8746982b5100764db289,PMC,"Viral Etiology of acute respiratory tract infections in hospitalized children and adults in Shandong Province, China",http://dx.doi.org/10.1186/s12985-015-0388-z,PMC4606902,26467854,CC BY,"BACKGROUND: The dominant viral etiologies responsible for acute respiratory infections (ARIs) are poorly understood, particularly among hospitalized patients. Improved etiological insight is needed to improve clinical management and prevention of ARIs. METHODS: Clinical and demographic information and throat swabs were collected from 607 patients from 2011 to 2013 in Shandong Province, China. Multiplex RT-PCR (SeeplexTM RV detection, Seegene) was performed to detected 12 respiratory viral pathogens. RESULTS: A total of 607 hospitalized patients were enrolled from 2011 to 2013. Viruses were identified in 35.75 % (217/607) of cases, including 78 influenza virus A and B (IVA and IVB), 47 para-influenza viruses (PIVs), 41 respiratory syncytial virus (RSV) and 38 adenovirus (ADV). For the children under 15 year old, the common detected viruses were influenza viruses, RSV, PIVS and ADV, while the principal respiratory viruses were human coronaviruses (HCoV), PIVs, influenza viruses for the old adults. Co-infections with multiple viruses were detected in 15.67 % of patients. Children under 5 years were more likely to have one or more detectable virus associated with their ARI. The peak of ARI caused by the respiratory viruses occurred in winter. CONCLUSION: This study demonstrated respiratory viruses were the major cause of hospitalized ARI patients in Shandong Province, influenza virus was the most common detected, RSV was the highest incidence among the young children (≤5 years). These findings also gave a better understand of virus distribution among different age and seasons, which help to consider potential therapeutic approaches and develop effective prevention strategies for respiratory virus infection.",2015 Oct 14,"['Liu, Ti', 'Li, Zhong', 'Zhang, Shengyang', 'Song, Shaoxia', 'Julong, Wu', 'Lin, Yi', 'Guo, Nongjian', 'Xing, Chunyan', 'Xu, Aiqiang', 'Bi, Zhenqiang', 'Wang, Xianjun']",Virol J,,,True
732dff5e34c82bab1a77fe07eeff62b1a0e44fa7,PMC,Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation,http://dx.doi.org/10.1371/journal.pone.0140674,PMC4607159,26469793,CC BY,"BACKGROUND AND OBJECTIVES: Although acute kidney injury (AKI) is the most frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), few studies have been conducted on the risk factors of AKI. We performed this study to identify the risk factors of AKI associated with in-hospital mortality. METHODS: Data from 322 adult patients receiving ECMO were analyzed. AKI and its stages were defined according to Kidney Disease Improving Global Outcomes (KDIGO) classifications. Variables within 24 h before ECMO insertion were collected and analyzed for the associations with AKI and in-hospital mortality. RESULTS: Stage 3 AKI was associated with in-hospital mortality, with a hazard ratio (HR) (95% CI) of 2.690 (1.472–4.915) compared to non-AKI (p = 0.001). The simplified acute physiology score 2 (SAPS2) and serum sodium level were also associated with in-hospital mortality, with HRs of 1.02 (1.004–1.035) per 1 score increase (p = 0.01) and 1.042 (1.014–1.070) per 1 mmol/L increase (p = 0.003). The initial pump speed of ECMO was significantly related to in-hospital mortality with a HR of 1.333 (1.020–1.742) per 1,000 rpm increase (p = 0.04). The pump speed was also associated with AKI (p = 0.02) and stage 3 AKI (p = 0.03) with ORs (95% CI) of 2.018 (1.129–3.609) and 1.576 (1.058–2.348), respectively. We also found that the red cell distribution width (RDW) above 14.1% was significantly related to stage 3 AKI. CONCLUSION: The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The RDW was a risk factor of stage 3 AKI.",2015 Oct 15,"['Lee, Sung Woo', 'Yu, Mi-yeon', 'Lee, Hajeong', 'Ahn, Shin Young', 'Kim, Sejoong', 'Chin, Ho Jun', 'Na, Ki Young']",PLoS One,,,True
6a86bf34d524aa5e33af0a550e4b3a6928d1e600,PMC,Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan,http://dx.doi.org/10.1186/s13054-015-1083-6,PMC4608327,26472401,CC BY,"INTRODUCTION: Community-acquired pneumonia (CAP) requires prompt treatment, but its diagnosis is complex. Improvement of bacterial CAP diagnosis by biomarkers has been evaluated using chest X-ray infiltrate as the CAP gold standard, producing conflicting results. We analyzed the diagnostic accuracy of biomarkers in suspected CAP adults visiting emergency departments for whom CAP diagnosis was established by an adjudication committee which founded its judgment on a systematic multidetector thoracic CT scan. METHODS: In an ancillary study of a multi-center prospective study evaluating the impact of systematic thoracic CT scan on CAP diagnosis, sensitivity and specificity of C-reactive protein (CRP) and procalcitonin (PCT) were evaluated. Systematic nasopharyngeal multiplex respiratory virus PCR was performed at inclusion. An adjudication committee classified CAP diagnostic probability on a 4-level Likert scale, based on all available data. RESULTS: Two hundred patients with suspected CAP were analyzed. The adjudication committee classified 98 patients (49.0 %) as definite CAP, 8 (4.0 %) as probable, 23 (11.5 %) as possible and excluded in 71 (35.5 %, including 29 patients with pulmonary infiltrates on chest X-ray). Among patients with radiological pulmonary infiltrate, 23 % were finally classified as excluded. Viruses were identified by PCR in 29 % of patients classified as definite. Area under the curve was 0.787 [95 % confidence interval (95 % CI), 0.717 to 0.857] for CRP and 0.655 (95 % CI, 0.570 to 0.739) for PCT to detect definite CAP. CRP threshold at 50 mg/L resulted in a positive predictive value of 0.76 and a negative predictive value of 0.75. No PCT cut-off resulted in satisfactory positive or negative predictive values. CRP and PCT accuracy was not improved by exclusion of the 25 (25.5 %) definite viral CAP cases. CONCLUSIONS: For patients with suspected CAP visiting emergency departments, diagnostic accuracy of CRP and PCT are insufficient to confirm the CAP diagnosis established using a gold standard that includes thoracic CT scan. Diagnostic accuracy of these biomarkers is also insufficient to distinguish bacterial CAP from viral CAP. TRIAL REGISTRATION: ClinicalTrials.gov registry NCT01574066 (February 7, 2012) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-1083-6) contains supplementary material, which is available to authorized users.",2015 Oct 16,"['Le Bel, Josselin', 'Hausfater, Pierre', 'Chenevier-Gobeaux, Camille', 'Blanc, François-Xavier', 'Benjoar, Mikhael', 'Ficko, Cécile', 'Ray, Patrick', 'Choquet, Christophe', 'Duval, Xavier', 'Claessens, Yann-Erick', None]",Crit Care,,,False
f4ccd54d01adf8df0ef201c6e7ab13d847c2a0f0,PMC,Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan,http://dx.doi.org/10.1186/s13054-015-1083-6,PMC4608327,26472401,CC BY,"INTRODUCTION: Community-acquired pneumonia (CAP) requires prompt treatment, but its diagnosis is complex. Improvement of bacterial CAP diagnosis by biomarkers has been evaluated using chest X-ray infiltrate as the CAP gold standard, producing conflicting results. We analyzed the diagnostic accuracy of biomarkers in suspected CAP adults visiting emergency departments for whom CAP diagnosis was established by an adjudication committee which founded its judgment on a systematic multidetector thoracic CT scan. METHODS: In an ancillary study of a multi-center prospective study evaluating the impact of systematic thoracic CT scan on CAP diagnosis, sensitivity and specificity of C-reactive protein (CRP) and procalcitonin (PCT) were evaluated. Systematic nasopharyngeal multiplex respiratory virus PCR was performed at inclusion. An adjudication committee classified CAP diagnostic probability on a 4-level Likert scale, based on all available data. RESULTS: Two hundred patients with suspected CAP were analyzed. The adjudication committee classified 98 patients (49.0 %) as definite CAP, 8 (4.0 %) as probable, 23 (11.5 %) as possible and excluded in 71 (35.5 %, including 29 patients with pulmonary infiltrates on chest X-ray). Among patients with radiological pulmonary infiltrate, 23 % were finally classified as excluded. Viruses were identified by PCR in 29 % of patients classified as definite. Area under the curve was 0.787 [95 % confidence interval (95 % CI), 0.717 to 0.857] for CRP and 0.655 (95 % CI, 0.570 to 0.739) for PCT to detect definite CAP. CRP threshold at 50 mg/L resulted in a positive predictive value of 0.76 and a negative predictive value of 0.75. No PCT cut-off resulted in satisfactory positive or negative predictive values. CRP and PCT accuracy was not improved by exclusion of the 25 (25.5 %) definite viral CAP cases. CONCLUSIONS: For patients with suspected CAP visiting emergency departments, diagnostic accuracy of CRP and PCT are insufficient to confirm the CAP diagnosis established using a gold standard that includes thoracic CT scan. Diagnostic accuracy of these biomarkers is also insufficient to distinguish bacterial CAP from viral CAP. TRIAL REGISTRATION: ClinicalTrials.gov registry NCT01574066 (February 7, 2012) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-1083-6) contains supplementary material, which is available to authorized users.",2015 Oct 16,"['Le Bel, Josselin', 'Hausfater, Pierre', 'Chenevier-Gobeaux, Camille', 'Blanc, François-Xavier', 'Benjoar, Mikhael', 'Ficko, Cécile', 'Ray, Patrick', 'Choquet, Christophe', 'Duval, Xavier', 'Claessens, Yann-Erick', None]",Crit Care,,,False
f3d150545162ff3cc253c235011a02a91ee676cb,PMC,Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan,http://dx.doi.org/10.1186/s13054-015-1083-6,PMC4608327,26472401,CC BY,"INTRODUCTION: Community-acquired pneumonia (CAP) requires prompt treatment, but its diagnosis is complex. Improvement of bacterial CAP diagnosis by biomarkers has been evaluated using chest X-ray infiltrate as the CAP gold standard, producing conflicting results. We analyzed the diagnostic accuracy of biomarkers in suspected CAP adults visiting emergency departments for whom CAP diagnosis was established by an adjudication committee which founded its judgment on a systematic multidetector thoracic CT scan. METHODS: In an ancillary study of a multi-center prospective study evaluating the impact of systematic thoracic CT scan on CAP diagnosis, sensitivity and specificity of C-reactive protein (CRP) and procalcitonin (PCT) were evaluated. Systematic nasopharyngeal multiplex respiratory virus PCR was performed at inclusion. An adjudication committee classified CAP diagnostic probability on a 4-level Likert scale, based on all available data. RESULTS: Two hundred patients with suspected CAP were analyzed. The adjudication committee classified 98 patients (49.0 %) as definite CAP, 8 (4.0 %) as probable, 23 (11.5 %) as possible and excluded in 71 (35.5 %, including 29 patients with pulmonary infiltrates on chest X-ray). Among patients with radiological pulmonary infiltrate, 23 % were finally classified as excluded. Viruses were identified by PCR in 29 % of patients classified as definite. Area under the curve was 0.787 [95 % confidence interval (95 % CI), 0.717 to 0.857] for CRP and 0.655 (95 % CI, 0.570 to 0.739) for PCT to detect definite CAP. CRP threshold at 50 mg/L resulted in a positive predictive value of 0.76 and a negative predictive value of 0.75. No PCT cut-off resulted in satisfactory positive or negative predictive values. CRP and PCT accuracy was not improved by exclusion of the 25 (25.5 %) definite viral CAP cases. CONCLUSIONS: For patients with suspected CAP visiting emergency departments, diagnostic accuracy of CRP and PCT are insufficient to confirm the CAP diagnosis established using a gold standard that includes thoracic CT scan. Diagnostic accuracy of these biomarkers is also insufficient to distinguish bacterial CAP from viral CAP. TRIAL REGISTRATION: ClinicalTrials.gov registry NCT01574066 (February 7, 2012) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-1083-6) contains supplementary material, which is available to authorized users.",2015 Oct 16,"['Le Bel, Josselin', 'Hausfater, Pierre', 'Chenevier-Gobeaux, Camille', 'Blanc, François-Xavier', 'Benjoar, Mikhael', 'Ficko, Cécile', 'Ray, Patrick', 'Choquet, Christophe', 'Duval, Xavier', 'Claessens, Yann-Erick', None]",Crit Care,,,True
906246292449c131afd43009c5863e51ab99efc1,PMC,Why Do We Feel Sick When Infected—Can Altruism Play a Role?,http://dx.doi.org/10.1371/journal.pbio.1002276,PMC4608734,26474156,CC BY,"When we contract an infection, we typically feel sick and behave accordingly. Symptoms of sickness behavior (SB) include anorexia, hypersomnia, depression, and reduced social interactions. SB affects species spanning from arthropods to vertebrates, is triggered nonspecifically by viruses, bacteria, and parasites, and is orchestrated by a complex network of cytokines and neuroendocrine pathways; clearly, it has been naturally selected. Nonetheless, SB seems evolutionarily costly: it promotes starvation and predation and reduces reproductive opportunities. How could SB persist? Former explanations focused on individual fitness, invoking improved resistance to pathogens. Could prevention of disease transmission, propagating in populations through kin selection, also contribute to SB?",2015 Oct 16,"['Shakhar, Keren', 'Shakhar, Guy']",PLoS Biol,,,True
f98d0564028d3963a79b75d9bd46fe5a1a5b8541,PMC,"Serological Evidence of MERS-CoV Antibodies in Dromedary Camels (Camelus dromedaries) in Laikipia County, Kenya",http://dx.doi.org/10.1371/journal.pone.0140125,PMC4608777,26473733,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently identified virus causing severe viral respiratory illness in people. Little is known about the reservoir in the Horn of Africa. In Kenya, where no human MERS cases have been reported, our survey of 335 dromedary camels, representing nine herds in Laikipia County, showed a high seroprevalence (46.9%) to MERS-CoV antibodies. Between herd differences were present (14.3%– 82.9%), but was not related to management type or herd isolation. Further research should focus on identifying similarity between MERS-CoV viral isolates in Kenya and clinical isolates from the Middle East and elsewhere.",2015 Oct 16,"['Deem, Sharon L.', 'Fèvre, Eric M.', 'Kinnaird, Margaret', 'Browne, A. Springer', 'Muloi, Dishon', 'Godeke, Gert-Jan', 'Koopmans, Marion', 'Reusken, Chantal B.']",PLoS One,,,True
41ed8edac17db0256c043cee4b27884395539746,PMC,Global Dynamics of a Virus Dynamical Model with Cell-to-Cell Transmission and Cure Rate,http://dx.doi.org/10.1155/2015/758362,PMC4609528,26504489,CC BY,"The cure effect of a virus model with both cell-to-cell transmission and cell-to-virus transmission is studied. By the method of next generation matrix, the basic reproduction number is obtained. The locally asymptotic stability of the virus-free equilibrium and the endemic equilibrium is considered by investigating the characteristic equation of the model. The globally asymptotic stability of the virus-free equilibrium is proved by constructing suitable Lyapunov function, and the sufficient condition for the globally asymptotic stability of the endemic equilibrium is obtained by constructing suitable Lyapunov function and using LaSalle invariance principal.",2015 Oct 1,"['Zhang, Tongqian', 'Meng, Xinzhu', 'Zhang, Tonghua']",Comput Math Methods Med,,,True
d44571bd848bc813e4cdd2fe8c36b922433ec4da,PMC,Infection as an Environmental Trigger of Multiple Sclerosis Disease Exacerbation,http://dx.doi.org/10.3389/fimmu.2015.00520,PMC4609887,26539193,CC BY,"Over the past several decades, significant advances have been made in identifying factors that contribute to the pathogenesis of multiple sclerosis (MS) and have culminated in the approval of some effective therapeutic strategies for disease intervention. However, the mechanisms by which environmental factors, such as infection, contribute to the pathogenesis and/or symptom exacerbation remain to be fully elucidated. Relapse frequency in MS patients contributes to neurological impairment and, in the initial phases of disease, serves as a predictor of poor disease prognosis. The purpose of this review is to examine the evidence that supports a role for peripheral infection in modulating the natural history of this disease. Evidence supporting a role for infection in promoting exacerbation in animal models of MS is also reviewed. Finally, a few mechanisms by which infection may exacerbate symptoms of MS and other neurological diseases are discussed. Those who comprise the majority of MS patients acquire approximately two upper-respiratory infections per year; furthermore, this type of infection doubles the risk for MS relapse, underscoring the contribution of this relationship as being potentially important and particularly detrimental.",2015 Oct 19,"Steelman, Andrew J.",Front Immunol,,,True
aa833047a4b1e39dcdacffc2d5e219ffa4ddb06b,PMC,"Big city, small world: density, contact rates, and transmission of dengue across Pakistan",http://dx.doi.org/10.1098/rsif.2015.0468,PMC4614486,26468065,CC BY,"Macroscopic descriptions of populations commonly assume that encounters between individuals are well mixed; i.e. each individual has an equal chance of coming into contact with any other individual. Relaxing this assumption can be challenging though, due to the difficulty of acquiring detailed knowledge about the non-random nature of encounters. Here, we fitted a mathematical model of dengue virus transmission to spatial time-series data from Pakistan and compared maximum-likelihood estimates of ‘mixing parameters’ when disaggregating data across an urban–rural gradient. We show that dynamics across this gradient are subject not only to differing transmission intensities but also to differing strengths of nonlinearity due to differences in mixing. Accounting for differences in mobility by incorporating two fine-scale, density-dependent covariate layers eliminates differences in mixing but results in a doubling of the estimated transmission potential of the large urban district of Lahore. We furthermore show that neglecting spatial variation in mixing can lead to substantial underestimates of the level of effort needed to control a pathogen with vaccines or other interventions. We complement this analysis with estimates of the relationships between dengue transmission intensity and other putative environmental drivers thereof.",2015 Oct 6,"['Kraemer, M. U. G.', 'Perkins, T. A.', 'Cummings, D. A. T.', 'Zakar, R.', 'Hay, S. I.', 'Smith, D. L.', 'Reiner, R. C.']",J R Soc Interface,,,True
c125f2b3071406f51b9b9aee860030b2f402ee77,PMC,Alterations in stress granule dynamics driven by TDP-43 and FUS: a link to pathological inclusions in ALS?,http://dx.doi.org/10.3389/fncel.2015.00423,PMC4615823,26557057,CC BY,"Stress granules (SGs) are RNA-containing cytoplasmic foci formed in response to stress exposure. Since their discovery in 1999, over 120 proteins have been described to be localized to these structures (in 154 publications). Most of these components are RNA binding proteins (RBPs) or are involved in RNA metabolism and translation. SGs have been linked to several pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In ALS and FTD, the majority of cases have no known etiology and exposure to external stress is frequently proposed as a contributor to either disease initiation or the rate of disease progression. Of note, both ALS and FTD are characterized by pathological inclusions, where some well-known SG markers localize with the ALS related proteins TDP-43 and FUS. We propose that TDP-43 and FUS serve as an interface between genetic susceptibility and environmental stress exposure in disease pathogenesis. Here, we will discuss the role of TDP-43 and FUS in SG dynamics and how disease-linked mutations affect this process.",2015 Oct 23,"['Aulas, Anaïs', 'Vande Velde, Christine']",Front Cell Neurosci,,,True
409e8fa9c8b69d7982ac0ecc28437a2e8a246d2a,PMC,Strengthening epidemiologic investigation of infectious diseases in Korea: lessons from the Middle East Respiratory Syndrome outbreak,http://dx.doi.org/10.4178/epih/e2015040,PMC4616012,26493654,CC BY,"The recent outbreak of Middle East Respiratory Syndrome (MERS) coronavirus infection in Korea resulted in large socioeconomic losses. This provoked the Korean government and the general public to recognize the importance of having a well-established system against infectious diseases. Although epidemiologic investigation is one of the most important aspects of prevention, it has been pointed out that much needs to be improved in Korea. We review here the current status of the Korean epidemiologic service and suggest possible supplementation measures. We examine the current national preventive infrastructure, including human resources such as Epidemic Intelligence Service officers, its governmental management, and related policies. In addition, we describe the practical application of these resources to the recent MERS outbreak and the progress in preventive measures. The spread of MERS demonstrated that the general readiness for emerging infectious diseases in Korea is considerably low. We believe that it is essential to increase society’s investment in disease prevention. Fostering public health personnel, legislating management policies, and establishing research centers for emerging infectious diseases are potential solutions. Evaluating international preventive systems, developing cooperative measures, and initiating improvements are necessary. We evaluated the Korean epidemiologic investigation system and the public preventive measures against infectious diseases in light of the recent MERS outbreak. We suggest that governmental authorities in Korea enforce preventive policies, foster the development of highly qualified personnel, and increase investment in the public health domain of infectious disease prevention.",2015 Sep 16,"['Lee, Changhwan', 'Ki, Moran']",Epidemiol Health,,,True
2386a5c1d03abfd621c25515dcb087174ff54e0a,PMC,Strengthening epidemiologic investigation of infectious diseases in Korea: lessons from the Middle East Respiratory Syndrome outbreak,http://dx.doi.org/10.4178/epih/e2015040,PMC4616012,26493654,CC BY,"The recent outbreak of Middle East Respiratory Syndrome (MERS) coronavirus infection in Korea resulted in large socioeconomic losses. This provoked the Korean government and the general public to recognize the importance of having a well-established system against infectious diseases. Although epidemiologic investigation is one of the most important aspects of prevention, it has been pointed out that much needs to be improved in Korea. We review here the current status of the Korean epidemiologic service and suggest possible supplementation measures. We examine the current national preventive infrastructure, including human resources such as Epidemic Intelligence Service officers, its governmental management, and related policies. In addition, we describe the practical application of these resources to the recent MERS outbreak and the progress in preventive measures. The spread of MERS demonstrated that the general readiness for emerging infectious diseases in Korea is considerably low. We believe that it is essential to increase society’s investment in disease prevention. Fostering public health personnel, legislating management policies, and establishing research centers for emerging infectious diseases are potential solutions. Evaluating international preventive systems, developing cooperative measures, and initiating improvements are necessary. We evaluated the Korean epidemiologic investigation system and the public preventive measures against infectious diseases in light of the recent MERS outbreak. We suggest that governmental authorities in Korea enforce preventive policies, foster the development of highly qualified personnel, and increase investment in the public health domain of infectious disease prevention.",2015 Sep 16,"['Lee, Changhwan', 'Ki, Moran']",Epidemiol Health,,,False
fb6c8bb97e2115a2551f7a278889f3dd54c538fb,PMC,Islet Xeno/transplantation and the risk of contagion: local responses from Canada and Australia to an emerging global technoscience,http://dx.doi.org/10.1186/s40504-015-0030-2,PMC4617985,26497322,CC BY,"This paper situates the public debate over the use of living animal organs and tissue for human therapies within the history of experimental islet transplantation. Specifically, the paper compares and contrasts the Canadian and Australian responses on xenotransplantation to consider what lessons can be learnt about the regulation of a complex and controversial biotechnology. Sobbrio and Jorqui described public engagement on xenotransplantation in these countries as ‘important forms of experimental democracy.’ While Canada experimented with a novel nation-wide public consultation, Australia sought public input within the context of a national inquiry. In both instances, the outcome was a temporary moratorium on all forms of clinical xenotransplantation comparable to the policies adopted in some European countries. In addition, the Australian xenotransplantation ban coincided with a temporary global ban on experimental islet allotransplantation in 2007. Through historical and comparative research, this paper investigates how public controversies over organ and tissue transplantation can inform our understanding of the mediation of interspeciality and the regulation of a highly contested technoscience. It offers an alternative perspective on the xenotransplantation controversy by exploring the ways in which coinciding moratoriums on islet allograft and xenograft challenge, complicate and confound our assumptions regarding the relationships between human and animal, between routine surgery and clinical experimentation, between biomedical science and social science, and between disease risks and material contagion.",2015 Oct 23,"Cheng, Myra",Life Sci Soc Policy,,,True
e6b8ff26b423ef6507f006d69f9a183fb1147988,PMC,The More the Better? A Comparison of the Information Sources Used by the Public during Two Infectious Disease Outbreaks,http://dx.doi.org/10.1371/journal.pone.0140028,PMC4618063,26485302,CC BY,"Recent infectious disease outbreaks have resulted in renewed recognition of the importance of risk communication planning and execution to public health control strategies. Key to these efforts is public access to information that is understandable, reliable and meets their needs for informed decision-making on protective health behaviours. Learning from the trends in sources used in previous outbreaks will enable improvements in information access in future outbreaks. Two separate random-digit dialled telephone surveys were conducted in Alberta, Canada, to explore information sources used by the public, together with their perceived usefulness and credibility, during the 2003 Severe Acute Respiratory Syndrome (SARS) epidemic (n = 1209) and 2009–2010 H1N1 pandemic (n = 1206). Traditional mass media were the most used information sources in both surveys. Although use of the Internet increased from 25% during SARS to 56% during H1N1, overall use of social media was not as high as anticipated. Friends and relatives were commonly used as an information source, but were not deemed very useful or credible. Conversely, doctors and health professionals were considered credible, but not consulted as frequently. The use of five or more information sources increased by almost 60% between the SARS and H1N1 surveys. There was a shift to older, more educated and more affluent respondents between the surveys, most likely caused by a decrease in the use of landlines amongst younger Canadians. It was concluded that people are increasingly using multiple sources of health risk information, presumably in a complementary manner. Subsequently, although using online media is important, this should be used to augment rather than replace more traditional information channels. Efforts should be made to improve knowledge transfer to health care professionals and doctors and provide them with opportunities to be more accessible as information sources. Finally, the future use of telephone surveys needs to account for the changing demographics of the respondents accessed through such surveys.",2015 Oct 20,"['Jardine, Cynthia G.', 'Boerner, Franziska U.', 'Boyd, Amanda D.', 'Driedger, S. Michelle']",PLoS One,,,True
cd67f336a7356dd88e971d3541829bdc290257f4,PMC,Evaluating Subcriticality during the Ebola Epidemic in West Africa,http://dx.doi.org/10.1371/journal.pone.0140651,PMC4618845,26484544,CC BY,"The 2014–2015 Ebola outbreak is the largest and most widespread to date. In order to estimate ongoing transmission in the affected countries, we estimated the weekly average number of secondary cases caused by one individual infected with Ebola throughout the infectious period for each affected West African country using a stochastic hidden Markov model fitted to case data from the World Health Organization. If the average number of infections caused by one Ebola infection is less than 1.0, the epidemic is subcritical and cannot sustain itself. The epidemics in Liberia and Sierra Leone have approached subcriticality at some point during the epidemic; the epidemic in Guinea is ongoing with no evidence that it is subcritical. Response efforts to control the epidemic should continue in order to eliminate Ebola cases in West Africa.",2015 Oct 20,"['Enanoria, Wayne T. A.', 'Worden, Lee', 'Liu, Fengchen', 'Gao, Daozhou', 'Ackley, Sarah', 'Scott, James', 'Deiner, Michael', 'Mwebaze, Ernest', 'Ip, Wui', 'Lietman, Thomas M.', 'Porco, Travis C.']",PLoS One,,,True
417754f2c930dac6e586d36eb8bfb07355f6e0ff,PMC,Feasibility of a birth cohort study dedicated to assessing acute infections using symptom diaries and parental collection of biomaterials,http://dx.doi.org/10.1186/s12879-015-1189-0,PMC4618955,26493700,CC BY,"BACKGROUND: A birth cohort dedicated to studying infections in early childhood may be assisted by parental recording of symptoms on a daily basis and a collection of biomaterials. We aimed at testing the feasibility of this approach for use in a long-term study focusing on infections in children in Germany. METHODS: Parents of 1- to 3-year-old children (n = 75) were recruited in nursery schools. They were asked to complete a symptom diary on a daily basis and to take monthly and symptom-triggered nasal swabs and stool samples from their child over the study period of three months. Feasibility was measured by means of the return proportions of symptom diaries and bio samples; acceptance was assessed by a questionnaire delivered to participants at the end of the study. RESULTS: The majority of the participants filled in the symptom diary during the three months study for 75 or more days (77.3 %), and provided the monthly nasal swabs (62.7 %) and stool samples (65.3 %). The time needed for the tasks was acceptable for most participants (symptom diary: 92.3 %, nasal swabs: 98.5 %, stool samples: 100.0 %). In 64.3 % of the symptom-triggered nasal swabs, respiratory viruses were found compared to 55.5 % in throat swabs taken by health-care professionals within the “ARE surveillance Lower Saxony”, a special project by the Governmental Institute of Public Health of Lower Saxony to investigate causal pathogens for acute respiratory infections in children. CONCLUSIONS: The parental assessment of symptoms and collection of biomaterials in a birth cohort dedicated to studying infections appears feasible in a middle class German population. The success of the study will depend on the ability to maintain these activities over a long time period. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1189-0) contains supplementary material, which is available to authorized users.",2015 Oct 22,"['Zoch, Beate', 'Karch, André', 'Dreesman, Johannes', 'Monazahian, Masyar', 'Baillot, Armin', 'Mikolajczyk, Rafael T.']",BMC Infect Dis,,,True
62189c3e0d5823002bc5785f7acc61d89fb85666,PMC,Design and optimization of peptide nanoparticles,http://dx.doi.org/10.1186/s12951-015-0119-z,PMC4619341,26498651,CC BY,"BACKGROUND: Various supra-molecular structures form by self-assembly of proteins in a symmetric fashion. Examples of such structures are viruses, some bacterial micro-compartments and eukaryotic vaults. Peptide/protein-based nanoparticles are emerging in synthetic biology for a variety of biomedical applications, mainly as drug targeting and delivery systems or as vaccines. Our self-assembling peptide nanoparticles (SAPNs) are formed by a single peptide chain that consists of two helical coiled-coil segments connected by a short linker region. One helix is forming a pentameric coiled coil while the other is forming a trimeric coiled coil. RESULTS: Here, we were studying in vitro and in silico the effect of the chain length and of point mutations near the linker region between the pentamer and the trimer on the self-assembly of the SAPNs. 60 identical peptide chains co-assemble to form a spherical nanoparticle displaying icosahedral symmetry. We have stepwise reduced the size of the protein chain to a minimal chain length of 36 amino acids. We first used biochemical and biophysical methods on the longer constructs followed by molecular dynamics simulations to study eleven different smaller peptide constructs. We have identified one peptide that shows the most promising mini-nanoparticle model in silico. CONCLUSIONS: An approach of in silico modeling combined with in vitro testing and verification yielded promising peptide designs: at a minimal chain length of only 36 amino acids they were able to self-assemble into proper nanoparticles. This is important since the production cost increases more than linearly with chain length. Also the size of the nanoparticles is significantly smaller than 20 nm, thus reducing the immunogenicity of the particles, which in turn may allow to use the SAPNs as drug delivery systems without the risk of an anaphylactic shock. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12951-015-0119-z) contains supplementary material, which is available to authorized users.",2015 Oct 24,"['Doll, Tais A. P. F.', 'Dey, Raja', 'Burkhard, Peter']",J Nanobiotechnology,,,True
693b013cbc9a762c6116b82a671e2eb24b1731b6,PMC,Antibody Derived Peptides for Detection of Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.pone.0135859,PMC4619498,26489048,CC BY,"BACKGROUND: Current Ebola virus (EBOV) detection methods are costly and impractical for epidemic scenarios. Different immune-based assays have been reported for the detection and quantification of Ebola virus (EBOV) proteins. In particular, several monoclonal antibodies (mAbs) have been described that bind the capsid glycoprotein (GP) of EBOV GP. However, the currently available platforms for the design and production of full-length mAbs are cumbersome and costly. The use of antibody fragments, rather than full-length antibodies, might represent a cost-effective alternative for the development of diagnostic and possibly even therapeutic alternatives for EBOV. METHODS/PRINCIPAL FINDINGS: We report the design and expression of three recombinant anti-GP mAb fragments in Escherichia coli cultures. These fragments contained the heavy and light variable portions of the three well-studied anti-GP full-length mAbs 13C6, 13F6, and KZ52, and are consequently named scFv-13C6, scFv-13F6, and Fab-KZ52, respectively. All three fragments exhibited specific anti-GP binding activity in ELISA experiments comparable to that of full-length anti-GP antibodies (i.e., the same order of magnitude) and they are easily and economically produced in bacterial cultures. CONCLUSION/SIGNIFICANCE: Antibody fragments might represent a useful, effective, and low cost alternative to full-length antibodies in Ebola related capture and diagnostics applications.",2015 Oct 21,"['Rodríguez-Martínez, Luis Mario', 'Marquez-Ipiña, Alan Roberto', 'López-Pacheco, Felipe', 'Pérez-Chavarría, Roberto', 'González-Vázquez, Juan Carlos', 'González-González, Everardo', 'Trujillo-de Santiago, Grissel', 'Ponce-Ponce de León, César Alejandro', 'Zhang, Yu Shrike', 'Dokmeci, Mehmet Remzi', 'Khademhosseini, Ali', 'Alvarez, Mario Moisés']",PLoS One,,,True
1926a717f92225eb7539c0fe190cefe1b067f08e,PMC,Assessment of reference gene stability in Rice stripe virus and Rice black streaked dwarf virus infection rice by quantitative Real-time PCR,http://dx.doi.org/10.1186/s12985-015-0405-2,PMC4619528,26497487,CC BY,"BACKGROUND: Stably expressed reference gene(s) normalization is important for the understanding of gene expression patterns by quantitative Real-time PCR (RT-qPCR), particularly for Rice stripe virus (RSV) and Rice black streaked dwarf virus (RBSDV) that caused seriously damage on rice plants in China and Southeast Asia. METHODS: The expression of fourteen common used reference genes of Oryza sativa L. were evaluated by RT-qPCR in RSV and RBSDV infected rice plants. Suitable normalization reference gene(s) were identified by geNorm and NormFinder algorithms. RESULTS: UBQ 10 + GAPDH and UBC + Actin1 were identified as suitable reference genes for RT-qPCR normalization under RSV and RBSDV infection, respectively. When using multiple reference genes, the expression patterns of OsPRIb and OsWRKY, two virus resistance genes, were approximately similar with that reported previously. Comparatively, by using single reference gene (TIP41-Like), a weaker inducible response was observed. CONCLUSIONS: We proposed that the combination of two reference genes could obtain more accurate and reliable normalization of RT-qPCR results in RSV- and RBSDV-infected plants. This work therefore sheds light on establishing a standardized RT-qPCR procedure in RSV- and RBSDV-infected rice plants, and might serve as an important point for discovering complex regulatory networks and identifying genes relevant to biological processes or implicated in virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0405-2) contains supplementary material, which is available to authorized users.",2015 Oct 24,"['Fang, Peng', 'Lu, Rongfei', 'Sun, Feng', 'Lan, Ying', 'Shen, Wenbiao', 'Du, Linlin', 'Zhou, Yijun', 'Zhou, Tong']",Virol J,,,True
8b33d1cedd5e6f39a2609b233d7070e3ddf52831,PMC,Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III,http://dx.doi.org/10.1371/journal.pntd.0004167,PMC4619746,26495991,CC0,"Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H(2)O(2), but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H(2)O(2), which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines.",2015 Oct 23,"['Fan, Yi-Chin', 'Chiu, Hsien-Chung', 'Chen, Li-Kuang', 'Chang, Gwong-Jen J.', 'Chiou, Shyan-Song']",PLoS Negl Trop Dis,,,True
e1f5129f1f4480a910c93ff7bb33fec50d68feea,PMC,Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III,http://dx.doi.org/10.1371/journal.pntd.0004167,PMC4619746,26495991,CC0,"Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H(2)O(2), but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H(2)O(2), which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines.",2015 Oct 23,"['Fan, Yi-Chin', 'Chiu, Hsien-Chung', 'Chen, Li-Kuang', 'Chang, Gwong-Jen J.', 'Chiou, Shyan-Song']",PLoS Negl Trop Dis,,,False
1f408749f93253eda073910a5b05fcc8e01eead2,PMC,Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III,http://dx.doi.org/10.1371/journal.pntd.0004167,PMC4619746,26495991,CC0,"Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H(2)O(2), but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H(2)O(2), which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines.",2015 Oct 23,"['Fan, Yi-Chin', 'Chiu, Hsien-Chung', 'Chen, Li-Kuang', 'Chang, Gwong-Jen J.', 'Chiou, Shyan-Song']",PLoS Negl Trop Dis,,,False
b4c0e3c28f1d56b15dc109d4a59731161e07fb41,PMC,Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III,http://dx.doi.org/10.1371/journal.pntd.0004167,PMC4619746,26495991,CC0,"Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H(2)O(2), but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H(2)O(2), which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines.",2015 Oct 23,"['Fan, Yi-Chin', 'Chiu, Hsien-Chung', 'Chen, Li-Kuang', 'Chang, Gwong-Jen J.', 'Chiou, Shyan-Song']",PLoS Negl Trop Dis,,,False
f782959399ba9e5b1f5e79e35c20b62eb765379c,PMC,Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III,http://dx.doi.org/10.1371/journal.pntd.0004167,PMC4619746,26495991,CC0,"Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H(2)O(2), but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H(2)O(2), which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines.",2015 Oct 23,"['Fan, Yi-Chin', 'Chiu, Hsien-Chung', 'Chen, Li-Kuang', 'Chang, Gwong-Jen J.', 'Chiou, Shyan-Song']",PLoS Negl Trop Dis,,,False
a46d2cd0e65ba71e9d1ccf20762c9043ed3e67c2,PMC,Prognosis of nonspecific interstitial pneumonia correlates with perivascular CD4+ T lymphocyte infiltration of the lung,http://dx.doi.org/10.1186/s12890-015-0122-z,PMC4619990,26496721,CC BY,"BACKGROUND: Nonspecific interstitial pneumonia (NSIP) is characterized by interstitial infiltration of T lymphocytes, and subpopulations of these cells may be associated with the progression of fibrosis. However, few studies evaluate the correlation of prognosis with this characteristic. Therefore, we performed morphological and quantitative analyses of T lymphocytes in patients with NSIP and evaluated the relationship between T lymphocytes and prognosis. METHODS: Immunohistochemistry was used to detect the presence of CD4+ and CD8+ T lymphocytes in 55 biopsies of patients with NSIP to determine the numbers of these T cell subpopulations in lymphoid follicles as well as in perivascular, interstitial, and peribronchial anatomical compartments. The relationship between CD4+ and CD8+ T lymphocyte populations and prognosis was analyzed. RESULTS: The mean age of 55 patients was 48.9 ± 10.5 years, and 36 (65 %) of patients were women. All patients were followed for a mean duration of 46 ± 25 months. Thirteen (23.6 %) patients died during follow-up. Perivascular CD4+ lymphocyte infiltration (HR, 0.939; 95 % CI, 0.883–0.999; p = 0.048) was an independent risk factor for survival. Perivascular infiltrates of CD4+ T lymphocytes correlated with survival time (r = 0.270, p = 0.046). Patients with improved forced vital capacity survived longer and had higher numbers of CD4+ T lymphocytes that infiltrated perivascular tissue. The densities of CD4+ and CD8+ T lymphocytes infiltrating other tissues were not significantly associated with survival time. CONCLUSIONS: Perivascular infiltration of CD4+ T lymphocytes in patients with NSIP correlated with prognosis. The underlying mechanisms are unknown and require further studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12890-015-0122-z) contains supplementary material, which is available to authorized users.",2015 Oct 24,"['Qin, Ling', 'Wang, WenZe', 'Liu, HongRui', 'Xiao, Yi', 'Qin, MingWei', 'Zheng, WenJie', 'Shi, JuHong']",BMC Pulm Med,,,True
5c5088ded6a49170c4ee50c8a9bfc5422cc31668,PMC,"Trypsin- and low pH-mediated fusogenicity of avian metapneumovirus fusion proteins is determined by residues at positions 100, 101 and 294",http://dx.doi.org/10.1038/srep15584,PMC4620442,26498473,CC BY,"Avian metapneumovirus (aMPV) and human metapneumovirus (hMPV) are members of the genus Metapneumovirus in the subfamily Pneumovirinae. Metapneumovirus fusion (F) protein mediates the fusion of host cells with the virus membrane for infection. Trypsin- and/or low pH-induced membrane fusion is a strain-dependent phenomenon for hMPV. Here, we demonstrated that three subtypes of aMPV (aMPV/A, aMPV/B, and aMPV/C) F proteins promoted cell-cell fusion in the absence of trypsin. Indeed, in the presence of trypsin, only aMPV/C F protein fusogenicity was enhanced. Mutagenesis of the amino acids at position 100 and/or 101, located at a putative cleavage region in aMPV F proteins, revealed that the trypsin-mediated fusogenicity of aMPV F proteins is regulated by the residues at positions 100 and 101. Moreover, we demonstrated that aMPV/A and aMPV/B F proteins mediated cell-cell fusion independent of low pH, whereas the aMPV/C F protein did not. Mutagenesis of the residue at position 294 in the aMPV/A, aMPV/B, and aMPV/C F proteins showed that 294G played a critical role in F protein-mediated fusion under low pH conditions. These findings on aMPV F protein-induced cell-cell fusion provide new insights into the molecular mechanisms underlying membrane fusion and pathogenesis of aMPV.",2015 Oct 26,"['Yun, Bingling', 'Guan, Xiaolu', 'Liu, Yongzhen', 'Gao, Yanni', 'Wang, Yongqiang', 'Qi, Xiaole', 'Cui, Hongyu', 'Liu, Changjun', 'Zhang, Yanping', 'Gao, Li', 'Li, Kai', 'Gao, Honglei', 'Gao, Yulong', 'Wang, Xiaomei']",Sci Rep,,,True
e96735cc636261d9942b88273a0631b1006ec015,PMC,Remote Activation of Host Cell DNA Synthesis in Uninfected Cells Signaled by Infected Cells in Advance of Virus Transmission,http://dx.doi.org/10.1128/JVI.01950-15,PMC4621119,26311877,CC BY,"Viruses modulate cellular processes and metabolism in diverse ways, but these are almost universally studied in the infected cell itself. Here, we study spatial organization of DNA synthesis during multiround transmission of herpes simplex virus (HSV) using pulse-labeling with ethynyl nucleotides and cycloaddition of azide fluorophores. We report a hitherto unknown and unexpected outcome of virus-host interaction. Consistent with the current understanding of the single-step growth cycle, HSV suppresses host DNA synthesis and promotes viral DNA synthesis in spatially segregated compartments within the cell. In striking contrast, during progressive rounds of infection initiated at a single cell, we observe that infection induces a clear and pronounced stimulation of cellular DNA replication in remote uninfected cells. This induced DNA synthesis was observed in hundreds of uninfected cells at the extended border, outside the perimeter of the progressing infection. Moreover, using pulse-chase analysis, we show that this activation is maintained, resulting in a propagating wave of host DNA synthesis continually in advance of infection. As the virus reaches and infects these activated cells, host DNA synthesis is then shut off and replaced with virus DNA synthesis. Using nonpropagating viruses or conditioned medium, we demonstrate a paracrine effector of uninfected cell DNA synthesis in remote cells continually in advance of infection. These findings have significant implications, likely with broad applicability, for our understanding of the ways in which virus infection manipulates cell processes not only in the infected cell itself but also now in remote uninfected cells, as well as of mechanisms governing host DNA synthesis. IMPORTANCE We show that during infection initiated by a single particle with progressive cell-cell virus transmission (i.e., the normal situation), HSV induces host DNA synthesis in uninfected cells, mediated by a virus-induced paracrine effector. The field has had no conception that this process occurs, and the work changes our interpretation of virus-host interaction during advancing infection and has implications for understanding controls of host DNA synthesis. Our findings demonstrate the utility of chemical biology techniques in analysis of infection processes, reveal distinct processes when infection is examined in multiround transmission versus single-step growth curves, and reveal a hitherto-unknown process in virus infection, likely relevant for other viruses (and other infectious agents) and for remote signaling of other processes, including transcription and protein synthesis.",2015 Aug 26,"['Schmidt, Nora', 'Hennig, Thomas', 'Serwa, Remigiusz A.', 'Marchetti, Magda', ""O'Hare, Peter""]",J Virol,,,False
e622c993d64e1bdcb0b7ec5505945ab5fbe3185e,PMC,Remote Activation of Host Cell DNA Synthesis in Uninfected Cells Signaled by Infected Cells in Advance of Virus Transmission,http://dx.doi.org/10.1128/JVI.01950-15,PMC4621119,26311877,CC BY,"Viruses modulate cellular processes and metabolism in diverse ways, but these are almost universally studied in the infected cell itself. Here, we study spatial organization of DNA synthesis during multiround transmission of herpes simplex virus (HSV) using pulse-labeling with ethynyl nucleotides and cycloaddition of azide fluorophores. We report a hitherto unknown and unexpected outcome of virus-host interaction. Consistent with the current understanding of the single-step growth cycle, HSV suppresses host DNA synthesis and promotes viral DNA synthesis in spatially segregated compartments within the cell. In striking contrast, during progressive rounds of infection initiated at a single cell, we observe that infection induces a clear and pronounced stimulation of cellular DNA replication in remote uninfected cells. This induced DNA synthesis was observed in hundreds of uninfected cells at the extended border, outside the perimeter of the progressing infection. Moreover, using pulse-chase analysis, we show that this activation is maintained, resulting in a propagating wave of host DNA synthesis continually in advance of infection. As the virus reaches and infects these activated cells, host DNA synthesis is then shut off and replaced with virus DNA synthesis. Using nonpropagating viruses or conditioned medium, we demonstrate a paracrine effector of uninfected cell DNA synthesis in remote cells continually in advance of infection. These findings have significant implications, likely with broad applicability, for our understanding of the ways in which virus infection manipulates cell processes not only in the infected cell itself but also now in remote uninfected cells, as well as of mechanisms governing host DNA synthesis. IMPORTANCE We show that during infection initiated by a single particle with progressive cell-cell virus transmission (i.e., the normal situation), HSV induces host DNA synthesis in uninfected cells, mediated by a virus-induced paracrine effector. The field has had no conception that this process occurs, and the work changes our interpretation of virus-host interaction during advancing infection and has implications for understanding controls of host DNA synthesis. Our findings demonstrate the utility of chemical biology techniques in analysis of infection processes, reveal distinct processes when infection is examined in multiround transmission versus single-step growth curves, and reveal a hitherto-unknown process in virus infection, likely relevant for other viruses (and other infectious agents) and for remote signaling of other processes, including transcription and protein synthesis.",2015 Aug 26,"['Schmidt, Nora', 'Hennig, Thomas', 'Serwa, Remigiusz A.', 'Marchetti, Magda', ""O'Hare, Peter""]",J Virol,,,True
c16ef70e46b997661c4aef194fd79c1b902a3c39,PMC,"Do citation trends reflect epidemiologic patterns? Assessing MRSA, emerging and re-emerging pathogens, 1963–2014",http://dx.doi.org/10.1186/s12879-015-1182-7,PMC4621863,26502873,CC BY,"BACKGROUND: A rapid rise in PubMed citations on methicillin-resistant Staphylococcus aureus (MRSA) occurred after 2000, but the relationship of trends in citation to epidemiologic trends for infectious disease is not known. METHODS: We queried PubMed(R), for citations to the following: MRSA, HIV/AIDS, Staphylococcus aureus, severe acute respiratory syndrome, Lyme disease, avian influenza, West Nile virus, Chikungunya, Ebola virus and Middle Eastern respiratory syndrome. Incidence or mortality data were tabulated. RESULTS: We identified 560,225 citations in 1963–2014. There were two distinct qualitative citation patterns. Type I pathogens showed a decade of initial exponential growth. Type II pathogens showed a sudden spike in citations in a year or two, followed by a relative decline. MRSA most closely resembled a Type I pathogen. CONCLUSIONS: The Type I pattern pathogens had varied trends in disease incidence in the years following the exponential growth and subsequent decline in the number of citations. Their differing epidemiologic patterns did not correlate with their pattern of citations. We conclude that citation trends on MRSA cannot be used to determine past epidemiologic trends and also that the citation trend for MRSA in 1995–2011 most closely resembled that for HIV in 1981–1998.",2015 Oct 26,"['Morgan, Ethan', 'David, Michael Z.']",BMC Infect Dis,,,True
f5e971f5c6854bcf76a7963effbbd79e62becab0,PMC,Markedly Elevated Antibody Responses in Wild versus Captive Spotted Hyenas Show that Environmental and Ecological Factors Are Important Modulators of Immunity,http://dx.doi.org/10.1371/journal.pone.0137679,PMC4621877,26444876,CC BY,"Evolutionary processes have shaped the vertebrate immune system over time, but proximal mechanisms control the onset, duration, and intensity of immune responses. Based on testing of the hygiene hypothesis, it is now well known that microbial exposure is important for proper development and regulation of the immune system. However, few studies have examined the differences between wild animals in their natural environments, in which they are typically exposed to a wide array of potential pathogens, and their conspecifics living in captivity. Wild spotted hyenas (Crocuta crocuta) are regularly exposed to myriad pathogens, but there is little evidence of disease-induced mortality in wild hyena populations, suggesting that immune defenses are robust in this species. Here we assessed differences in immune defenses between wild spotted hyenas that inhabit their natural savanna environment and captive hyenas that inhabit a captive environment where pathogen control programs are implemented. Importantly, the captive population of spotted hyenas was derived directly from the wild population and has been in captivity for less than four generations. Our results show that wild hyenas have significantly higher serum antibody concentrations, including total IgG and IgM, natural antibodies, and autoantibodies than do captive hyenas; there was no difference in the bacterial killing capacity of sera collected from captive and wild hyenas. The striking differences in serum antibody concentrations observed here suggest that complementing traditional immunology studies, with comparative studies of wild animals in their natural environment may help to uncover links between environment and immune function, and facilitate progress towards answering immunological questions associated with the hygiene hypothesis.",2015 Oct 7,"['Flies, Andrew S.', 'Mansfield, Linda S.', 'Grant, Chris K.', 'Weldele, Mary L.', 'Holekamp, Kay E.']",PLoS One,,,True
aecb440fc8c84846d96359ffd450f3e24a00cdca,PMC,Redox process is crucial for inhibitory properties of aurintricarboxylic acid against activity of YopH: virulence factor of Yersinia pestis,,PMC4621896,26286963,CC BY,"YopH is a bacterial protein tyrosine phosphatase, which is essential for the viability and pathogenic virulence of the plague-causing Yersinia sp. bacteria. Inactivation of YopH activity would lead to the loss of bacterial pathogenicity. We have studied the inhibitory properties of aurintricarboxylic acid (ATA) against YopH phosphatase and found that at nanomolar concentrations ATA reversibly decreases the activity of YopH. Computational docking studies indicated that in all binding poses ATA binds in the YopH active site. Molecular dynamics simulations showed that in the predicted binding pose, ATA binds to the essential Cys403 and Arg409 residues in the active site and has a stronger binding affinity than the natural substrate (pTyr). The cyclic voltammetry experiments suggest that ATA reacts remarkably strongly with molecular oxygen. Additionally, the electrochemical reduction of ATA in the presence of a negative potential from −2.0 to 2.5 V generates a current signal, which is observed for hydrogen peroxide. Here we showed that ATA indicates a unique mechanism of YopH inactivation due to a redox process. We proposed that the potent inhibitory properties of ATA are a result of its strong binding in the YopH active site and in situ generation of hydrogen peroxide near catalytic cysteine residue.",2015 Jul 22,"['Kuban-Jankowska, Alicja', 'Sahu, Kamlesh K', 'Niedzialkowski, Pawel', 'Gorska, Magdalena', 'Tuszynski, Jack A', 'Ossowski, Tadeusz', 'Wozniak, Michal']",Oncotarget,,,True
1de0f645bef4bb4fa6244abca0b1e0396fdea449,PMC,"Etiology of community acquired pneumonia among children in India: prospective, cohort study",http://dx.doi.org/10.7189/jogh.05.020418,PMC4623579,26528392,CC BY,"BACKGROUND: Childhood community acquired pneumonia (CAP) is a significant problem in developing countries, and confirmation of microbial etiology is important for individual, as well as public health. However, there is paucity of data from a large cohort, examining multiple biological specimens for diverse pathogens (bacteria and viruses). The Community Acquired Pneumonia Etiology Study (CAPES) was designed to address this knowledge gap. METHODS: We enrolled children with CAP (based on WHO IMCI criteria of tachypnea with cough or breathing difficulty) over 24 consecutive months, and recorded presenting symptoms, risk factors, clinical signs, and chest radiography. We performed blood and nasopharyngeal aspirate (NPA) bacterial cultures, and serology (Mycoplasma pneumoniae, Chlamydophila pneumoniae). We also performed multiplex PCR for 25 bacterial/viral species in a subgroup representing 20% of the cohort. Children requiring endotracheal intubation underwent culture and PCR of bronchoalveolar lavage (BAL) specimens. FINDINGS: We enrolled 2345 children. NPA and blood cultures yielded bacteria in only 322 (13.7%) and 49 (2.1%) children respectively. In NPA, Streptococcus pneumoniae (79.1%) predominated, followed by Haemophilus influenzae (9.6%) and Staphylococcus aureus (6.8%). In blood, S. aureus (30.6%) dominated, followed by S. pneumoniae (20.4%) and Klebsiella pneumoniae (12.2%). M. pneumoniae and C. pneumoniae serology were positive in 4.3% and 1.1% respectively. Multiplex PCR in 428 NPA specimens identified organisms in 422 (98.6%); of these 352 (82.2%) had multiple organisms and only 70 (16.4%) had a single organism viz. S. pneumoniae: 35 (50%), Cytomegalovirus (CMV): 13 (18.6%), Respiratory Syncytial Virus (RSV): 9 (12.9%), other viruses: 6 (8.7%), S. aureus: 5 (7.1%), and H. influenzae: 2 (2.9%). BAL PCR (n = 30) identified single pathogens in 10 (S. pneumoniae–3, CMV–3, S. aureus–2, H. influenzae–2) and multiple pathogens in 18 children. There were 108 (4.6%) deaths. The pattern of pathogens identified did not correlate with pneumonia severity or mortality. CONCLUSIONS: The majority of children with CAP have multiple pathogens (bacteria and viruses). S. pneumoniae and S. aureus predominate in NPA and blood respectively. CMV and RSV were the dominant respiratory viruses in NPA and BAL. The presence of multiple pathogens, especially organisms associated with nasopharyngeal carriage, precludes confirmation of a causal relationship in most cases.",,"['Mathew, Joseph L.', 'Singhi, Sunit', 'Ray, Pallab', 'Hagel, Eva', 'Saghafian–Hedengren, Shanie', 'Bansal, Arun', 'Ygberg, Sofia', 'Sodhi, Kushaljit Singh', 'Kumar, B V Ravi', 'Nilsson, Anna']",J Glob Health.; 5(2):050418,,,True
aab34a745e83e2357628908ba583ef703632993d,PMC,"Etiology of community acquired pneumonia among children in India: prospective, cohort study",http://dx.doi.org/10.7189/jogh.05.020418,PMC4623579,26528392,CC BY,"BACKGROUND: Childhood community acquired pneumonia (CAP) is a significant problem in developing countries, and confirmation of microbial etiology is important for individual, as well as public health. However, there is paucity of data from a large cohort, examining multiple biological specimens for diverse pathogens (bacteria and viruses). The Community Acquired Pneumonia Etiology Study (CAPES) was designed to address this knowledge gap. METHODS: We enrolled children with CAP (based on WHO IMCI criteria of tachypnea with cough or breathing difficulty) over 24 consecutive months, and recorded presenting symptoms, risk factors, clinical signs, and chest radiography. We performed blood and nasopharyngeal aspirate (NPA) bacterial cultures, and serology (Mycoplasma pneumoniae, Chlamydophila pneumoniae). We also performed multiplex PCR for 25 bacterial/viral species in a subgroup representing 20% of the cohort. Children requiring endotracheal intubation underwent culture and PCR of bronchoalveolar lavage (BAL) specimens. FINDINGS: We enrolled 2345 children. NPA and blood cultures yielded bacteria in only 322 (13.7%) and 49 (2.1%) children respectively. In NPA, Streptococcus pneumoniae (79.1%) predominated, followed by Haemophilus influenzae (9.6%) and Staphylococcus aureus (6.8%). In blood, S. aureus (30.6%) dominated, followed by S. pneumoniae (20.4%) and Klebsiella pneumoniae (12.2%). M. pneumoniae and C. pneumoniae serology were positive in 4.3% and 1.1% respectively. Multiplex PCR in 428 NPA specimens identified organisms in 422 (98.6%); of these 352 (82.2%) had multiple organisms and only 70 (16.4%) had a single organism viz. S. pneumoniae: 35 (50%), Cytomegalovirus (CMV): 13 (18.6%), Respiratory Syncytial Virus (RSV): 9 (12.9%), other viruses: 6 (8.7%), S. aureus: 5 (7.1%), and H. influenzae: 2 (2.9%). BAL PCR (n = 30) identified single pathogens in 10 (S. pneumoniae–3, CMV–3, S. aureus–2, H. influenzae–2) and multiple pathogens in 18 children. There were 108 (4.6%) deaths. The pattern of pathogens identified did not correlate with pneumonia severity or mortality. CONCLUSIONS: The majority of children with CAP have multiple pathogens (bacteria and viruses). S. pneumoniae and S. aureus predominate in NPA and blood respectively. CMV and RSV were the dominant respiratory viruses in NPA and BAL. The presence of multiple pathogens, especially organisms associated with nasopharyngeal carriage, precludes confirmation of a causal relationship in most cases.",,"['Mathew, Joseph L.', 'Singhi, Sunit', 'Ray, Pallab', 'Hagel, Eva', 'Saghafian–Hedengren, Shanie', 'Bansal, Arun', 'Ygberg, Sofia', 'Sodhi, Kushaljit Singh', 'Kumar, B V Ravi', 'Nilsson, Anna']",J Glob Health.; 5(2):050418,,,False
b9a74f1f03a9b75351badb02e13448d1f65f7ed8,PMC,Inferring Infection Patterns Based on a Connectivity Map of Host Transcriptional Responses,http://dx.doi.org/10.1038/srep15820,PMC4623713,26508266,CC BY,"Host responses to infections represent an important pathogenicity determiner, and delineation of host responses can elucidate pathogenesis processes and inform the development of anti-infection therapies. Low cost, high throughput, easy quantitation, and rich descriptions have made gene expression profiling generated by DNA microarrays an optimal approach for describing host transcriptional responses (HTRs). However, efforts to characterize the landscape of HTRs to diverse pathogens are far from offering a comprehensive view. Here, we developed an HTR Connectivity Map based on systematic assessment of pairwise similarities of HTRs to 50 clinically important human pathogens using 1353 gene-expression profiles generated from >60 human cells/tissues. These 50 pathogens were further partitioned into eight robust “HTR communities” (i.e., groups with more consensus internal HTR similarities). These communities showed enrichment in specific infection attributes and differential gene expression patterns. Using query signatures of HTRs to external pathogens, we demonstrated four distinct modes of HTR associations among different pathogens types/class, and validated the reliability of the HTR community divisions for differentiating and categorizing pathogens from a host-oriented perspective. These findings provide a first-generation HTR Connectivity Map of 50 diverse pathogens, and demonstrate the potential for using annotated HTR community to detect functional associations among infectious pathogens.",2015 Oct 28,"['Han, Lu', 'He, Haochen', 'Li, Fei', 'Cui, Xiuliang', 'Xie, Dafei', 'Liu, Yang', 'Zheng, Xiaofei', 'Bai, Hui', 'Wang, Shengqi', 'Bo, Xiaochen']",Sci Rep,,,True
a4fe6d2a7e5129ad14c0af09390a13fdacdb01ee,PMC,Inferring Infection Patterns Based on a Connectivity Map of Host Transcriptional Responses,http://dx.doi.org/10.1038/srep15820,PMC4623713,26508266,CC BY,"Host responses to infections represent an important pathogenicity determiner, and delineation of host responses can elucidate pathogenesis processes and inform the development of anti-infection therapies. Low cost, high throughput, easy quantitation, and rich descriptions have made gene expression profiling generated by DNA microarrays an optimal approach for describing host transcriptional responses (HTRs). However, efforts to characterize the landscape of HTRs to diverse pathogens are far from offering a comprehensive view. Here, we developed an HTR Connectivity Map based on systematic assessment of pairwise similarities of HTRs to 50 clinically important human pathogens using 1353 gene-expression profiles generated from >60 human cells/tissues. These 50 pathogens were further partitioned into eight robust “HTR communities” (i.e., groups with more consensus internal HTR similarities). These communities showed enrichment in specific infection attributes and differential gene expression patterns. Using query signatures of HTRs to external pathogens, we demonstrated four distinct modes of HTR associations among different pathogens types/class, and validated the reliability of the HTR community divisions for differentiating and categorizing pathogens from a host-oriented perspective. These findings provide a first-generation HTR Connectivity Map of 50 diverse pathogens, and demonstrate the potential for using annotated HTR community to detect functional associations among infectious pathogens.",2015 Oct 28,"['Han, Lu', 'He, Haochen', 'Li, Fei', 'Cui, Xiuliang', 'Xie, Dafei', 'Liu, Yang', 'Zheng, Xiaofei', 'Bai, Hui', 'Wang, Shengqi', 'Bo, Xiaochen']",Sci Rep,,,False
8bb5f822c7bae1c50b1d5b7a9da329a1f9d8aee2,PMC,Transcriptomic Changes Due to Cytoplasmic TDP-43 Expression Reveal Dysregulation of Histone Transcripts and Nuclear Chromatin,http://dx.doi.org/10.1371/journal.pone.0141836,PMC4624943,26510133,CC BY,"TAR DNA-binding protein 43 (TDP-43) is normally a nuclear RNA-binding protein that exhibits a range of functions including regulation of alternative splicing, RNA trafficking, and RNA stability. However, in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), TDP-43 is abnormally phosphorylated, ubiquitinated, and cleaved, and is mislocalized to the cytoplasm where it forms distinctive aggregates. We previously developed a mouse model expressing human TDP-43 with a mutation in its nuclear localization signal (ΔNLS-hTDP-43) so that the protein preferentially localizes to the cytoplasm. These mice did not exhibit a significant number of cytoplasmic aggregates, but did display dramatic changes in gene expression as measured by microarray, suggesting that cytoplasmic TDP-43 may be associated with a toxic gain-of-function. Here, we analyze new RNA-sequencing data from the ΔNLS-hTDP-43 mouse model, together with published RNA-sequencing data obtained previously from TDP-43 antisense oligonucleotide (ASO) knockdown mice to investigate further the dysregulation of gene expression in the ΔNLS model. This analysis reveals that the transcriptomic effects of the overexpression of the ΔNLS-hTDP-43 transgene are likely due to a gain of cytoplasmic function. Moreover, cytoplasmic TDP-43 expression alters transcripts that regulate chromatin assembly, the nucleolus, lysosomal function, and histone 3’ untranslated region (UTR) processing. These transcriptomic alterations correlate with observed histologic abnormalities in heterochromatin structure and nuclear size in transgenic mouse and human brains.",2015 Oct 28,"['Amlie-Wolf, Alexandre', 'Ryvkin, Paul', 'Tong, Rui', 'Dragomir, Isabelle', 'Suh, EunRan', 'Xu, Yan', 'Van Deerlin, Vivianna M.', 'Gregory, Brian D.', 'Kwong, Linda K.', 'Trojanowski, John Q.', 'Lee, Virginia M.-Y.', 'Wang, Li-San', 'Lee, Edward B.']",PLoS One,,,True
3811a68dda2911cb406a2fbb448530aa2319ee21,PMC,Mucosal Immunogenicity of Genetically Modified Lactobacillus acidophilus Expressing an HIV-1 Epitope within the Surface Layer Protein,http://dx.doi.org/10.1371/journal.pone.0141713,PMC4624987,26509697,CC BY,"Surface layer proteins of probiotic lactobacilli are theoretically efficient epitope-displaying scaffolds for oral vaccine delivery due to their high expression levels and surface localization. In this study, we constructed genetically modified Lactobacillus acidophilus strains expressing the membrane proximal external region (MPER) from human immunodeficiency virus type 1 (HIV-1) within the context of the major S-layer protein, SlpA. Intragastric immunization of mice with the recombinants induced MPER-specific and S-layer protein-specific antibodies in serum and mucosal secretions. Moreover, analysis of systemic SlpA-specific cytokines revealed that the responses appeared to be Th1 and Th17 dominant. These findings demonstrated the potential use of the Lactobacillus S-layer protein for development of oral vaccines targeting specific peptides.",2015 Oct 28,"['Kajikawa, Akinobu', 'Zhang, Lin', 'LaVoy, Alora', 'Bumgardner, Sara', 'Klaenhammer, Todd R.', 'Dean, Gregg A.']",PLoS One,,,True
a65b8907068dde79fb7cc6e885a745607ed1f371,PMC,Vaccination Method Affects Immune Response and Bacterial Growth but Not Protection in the Salmonella Typhimurium Animal Model of Typhoid,http://dx.doi.org/10.1371/journal.pone.0141356,PMC4625024,26509599,CC BY,"Understanding immune responses elicited by vaccines, together with immune responses required for protection, is fundamental to designing effective vaccines and immunisation programs. This study examines the effects of the route of administration of a live attenuated vaccine on its interactions with, and stimulation of, the murine immune system as well as its ability to increase survival and provide protection from colonisation by a virulent challenge strain. We assess the effect of administration method using the murine model for typhoid, where animals are infected with S. Typhimurium. Mice were vaccinated either intravenously or orally with the same live attenuated S. Typhimurium strain and data were collected on vaccine strain growth, shedding and stimulation of antibodies and cytokines. Following vaccination, mice were challenged with a virulent strain of S. Typhimurium and the protection conferred by the different vaccination routes was measured in terms of challenge suppression and animal survival. The main difference in immune stimulation found in this study was the development of a secretory IgA response in orally-vaccinated mice, which was absent in IV vaccinated mice. While both strains showed similar protection in terms of challenge suppression in systemic organs (spleen and liver) as well as survival, they differed in terms of challenge suppression of virulent pathogens in gut-associated organs. This difference in gut colonisation presents important questions around the ability of vaccines to prevent shedding and transmission. These findings demonstrate that while protection conferred by two vaccines can appear to be the same, the mechanisms controlling the protection can differ and have important implications for infection dynamics within a population.",2015 Oct 28,"['Kinnear, Clare L.', 'Strugnell, Richard A.']",PLoS One,,,True
892fc12b9b9b6cf0030efee835b76a5c7879f0c2,PMC,An optimised method for the production of MERS-CoV spike expressing viral pseudotypes,http://dx.doi.org/10.1016/j.mex.2015.09.003,PMC4625112,26587388,CC BY,"The production and use of pseudotyped viral particles are widely established for many viruses, and applications in the fields of serology and vaccine development are manifold. Viral pseudotypes have proven to be powerful tools to study the effects of viral evolution on serological outcomes, viral tropism and immunogenicity studies. Pseudotyped viruses are chimeric constructs in which the outer (surface) glycoprotein(s) of one virus is combined with the replication-defective viral “core” of another virus. Pseudotypes allow for accurate, sequence-directed, sensitive antibody neutralisation assays and antiviral screening to be conducted within a low biosecurity facility and offer a safe and efficient alternative to wildtype virus use. The protocol outlined here represents a rapid and reliable method for the generation of high-titre pseudotype viral particles with the MERS-CoV spike protein on a lentiviral core, and is adapted from previously published protocols. This protocol is optimised for transfection in a 100 mm Petri dish with 7 ml of supernatant harvested, however it can be readily scaled to different production volumes. This protocol has a number of advantages including: • Use of readily available reagents. • Consistent, high virus titres. • Rapid generation of novel glycoproteins for research into strain variation.",2015 Oct 13,"['Grehan, K.', 'Ferrara, F.', 'Temperton, N.']",MethodsX,,,False
696e87c58213d9b59cac6ecc3c695a245772b081,PMC,Detection of immunoglobulin (Ig) A antibodies against porcine epidemic diarrhea virus (PEDV) in fecal and serum samples,http://dx.doi.org/10.1016/j.mex.2015.10.001,PMC4625113,26587386,CC BY,"Many assays for detection of antibodies against porcine epidemic diarrhea virus (PEDV) are based on detection of neutralizing antibodies or immunoglobulin (Ig) G in serum samples. However, due to the particular features of the mucosal immune system, presence of serum antibodies against enteric pathogens, such as PEDV, not always correlates with protection. In contrast, anti-PEDV IgA antibodies correlate with protection against subsequent challenges. An indirect PEDV IgA ELISA was previously developed to monitor IgA levels in colostrum and milk samples. In the present paper we describe an adaptation of the protocol for detection of IgA antibodies in serum and fecal samples. • The adapted protocol will aid in future assessment of protective levels of humoral response against PEDV infection by measuring IgA levels in serum and fecal samples. • Fecal samples are non-invasive and easy to collect at any time by animal caretakers and therefore offering advantages over the serum sample collection procedure. • A strong positive correlation between the anti-PEDV levels in fecal and serum samples was identified; however, detection of IgA antibodies was often more successful in serum than in paired fecal samples due to overall lower sample-to-positive (S/P) ratios for the latter sample type.",2015 Oct 13,"['Gerber, Priscilla F.', 'Opriessnig, Tanja']",MethodsX,,,False
67c9acbf8204919fe540d58d7db296b9210f1e90,PMC,Throat and nasal swabs for molecular detection of respiratory viruses in acute pharyngitis,http://dx.doi.org/10.1186/s12985-015-0408-z,PMC4625558,26511714,CC BY,"BACKGROUND: Detection of specific respiratory viruses is important for surveillance programs, where nasopharyngeal or nasal swabs have traditionally been used. Our objective was to determine whether sampling with a throat swab provides incremental benefit—when used in conjunction with a nasal swab—to detect respiratory viruses among patients with acute pharyngitis in the outpatient setting. FINDINGS: Among 83 university students with acute pharyngitis, we detected respiratory viruses with molecular assays on two samples collected per student: with a flocked nasal mid-turbinate swab and a rayon throat swab. Forty-eight (58 %) patients had virus-positive samples, with 49 virus positives detected by either swab (one patient had a dual viral co-infection). The most common viruses were rhinovirus, coronavirus, and influenza A virus. Specifically, 29 virus positives were detected by both swabs, 14 exclusively by the nasal swab, and six exclusively by the throat swab. The additional six virus positives detected by the throat swab corresponded to an absolute increase in viral detection of 7.1 % (95 % CI: 1.2–12.9 %); the specific viruses detected were four rhinoviruses and two coronaviruses. CONCLUSIONS: The flocked nasal swab samples respiratory viruses well, even among patients whose primary complaint is a sore throat. The rayon throat swab has modest incremental value over and above using the flocked nasal mid-turbinate swab alone, which suggests that while throat swabs alone would not be adequate for respiratory viral surveillance, they may have value as a supplementary test.",2015 Oct 29,"['Ali, Mohsin', 'Han, Sangsu', 'Gunst, Chris J.', 'Lim, Steve', 'Luinstra, Kathy', 'Smieja, Marek']",Virol J,,,True
ad79f4149f66651ceee0f251347fc5093294f68d,PMC,Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses,http://dx.doi.org/10.1186/s13567-015-0273-1,PMC4625562,26511922,CC BY,"Foot-and-mouth disease virus (FMDV) leader protein (L(pro)) is a papain-like proteinase, which plays an important role in FMDV pathogenesis. L(pro) exists as two forms, Lab and Lb, due to translation being initiated from two different start codons separated by 84 nucleotides. L(pro) self-cleaves from the nascent viral polyprotein precursor as the first mature viral protein. In addition to its role as a viral proteinase, L(pro) also has the ability to antagonize host antiviral effects. To promote FMDV replication, L(pro) can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β production; and (3) L(pro) can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules. In the light of recent functional and biochemical findings regarding L(pro), this review introduces the basic properties of L(pro) and the mechanisms by which it antagonizes host antiviral responses.",2015 Oct 28,"['Liu, Yingqi', 'Zhu, Zixiang', 'Zhang, Miaotao', 'Zheng, Haixue']",Vet Res,,,True
fd1b26543d016107178798ed466d39ecfe4572cc,PMC,Development of a rapid recombinase polymerase amplification assay for the detection of Streptococcus pneumoniae in whole blood,http://dx.doi.org/10.1186/s12879-015-1212-5,PMC4625855,26515409,CC BY,"BACKGROUND: Streptococcus pneumoniae is an important cause of microbial disease in humans. The introduction of multivalent vaccines has coincided with a dramatic decrease in the number of pneumococcal-related deaths. In spite of this, at a global level, pneumococcal infection remains an important cause of death among children under 5 years of age and in adults 65 years of age or older. In order to properly manage patients and control the spread of infection, a rapid and highly sensitive diagnostic method is needed for routine implementation, especially in resource-limited regions where pneumococcal disease is most prevalent. METHODS: Using the gene encoding leader peptidase A as a molecular diagnostics target, a real-time RPA assay was designed and optimised for the detection of S. pneumoniae in whole blood. The performance of the assay was compared to real-time PCR in terms of its analytical limit of detection and specificity. The inhibitory effect of human genomic DNA on amplification was investigated. The potential clinical utility of the assay was investigated using a small number of clinical samples. RESULTS: The RPA assay has a limit of detection equivalent to PCR (4.0 and 5.1 genome equivalents per reaction, respectively) and was capable of detecting the equivalent of <1 colony forming unit of S. pneumoniae when spiked into human whole blood. The RPA assay was 100 % inclusive (38/38 laboratory reference strains and 19/19 invasive clinical isolates) and 100 % exclusive; differentiating strains of S. pneumoniae species from other viridans group streptococci, including S. pseudopneumoniae. When applied to the analysis of a small number (n = 11) of clinical samples (blood culture positive for S. pneumoniae), the RPA assay was demonstrated to be both rapid and sensitive. CONCLUSIONS: The RPA assay developed in this work is shown to be as sensitive and as specific as PCR. In terms of reaction kinetics, the RPA assay is shown to exceed those of the PCR, with the RPA running to completion in 20 minutes and capable generating a positive signal in as little as 6 minutes. This work represents a potentially suitable assay for application in point-of-care settings.",2015 Oct 29,"['Clancy, Eoin', 'Higgins, Owen', 'Forrest, Matthew S.', 'Boo, Teck Wee', 'Cormican, Martin', 'Barry, Thomas', 'Piepenburg, Olaf', 'Smith, Terry J.']",BMC Infect Dis,,,True
4c76e1e9a4f5afc01accd2dbbd43f0463744e8d2,PMC,Effectively Communicating the Uncertainties Surrounding Ebola Virus Transmission,http://dx.doi.org/10.1371/journal.ppat.1005097,PMC4626028,26512988,CC BY,"The current Ebola virus outbreak has highlighted the uncertainties surrounding many aspects of Ebola virus virology, including routes of transmission. The scientific community played a leading role during the outbreak—potentially, the largest of its kind—as many of the questions surrounding ebolaviruses have only been interrogated in the laboratory. Scientists provided an invaluable resource for clinicians, public health officials, policy makers, and the lay public in understanding the progress of Ebola virus disease and the continuing outbreak. Not all of the scientific communication, however, was accurate or effective. There were multiple instances of published articles during the height of the outbreak containing potentially misleading scientific language that spurred media overreaction and potentially jeopardized preparedness and policy decisions at critical points. Here, we use articles declaring the potential for airborne transmission of Ebola virus as a case study in the inaccurate reporting of basic science, and we provide recommendations for improving the communication about unknown aspects of disease during public health crises.",2015 Oct 29,"['Kilianski, Andy', 'Evans, Nicholas G.']",PLoS Pathog,,,True
87c6c45d9946889a9a3551b31adff4c32c6c237e,PMC,Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine,http://dx.doi.org/10.1371/journal.ppat.1005215,PMC4626112,26513244,CC BY,"A SARS-CoV lacking the full-length E gene (SARS-CoV-∆E) was attenuated and an effective vaccine. Here, we show that this mutant virus regained fitness after serial passages in cell culture or in vivo, resulting in the partial duplication of the membrane gene or in the insertion of a new sequence in gene 8a, respectively. The chimeric proteins generated in cell culture increased virus fitness in vitro but remained attenuated in mice. In contrast, during SARS-CoV-∆E passage in mice, the virus incorporated a mutated variant of 8a protein, resulting in reversion to a virulent phenotype. When the full-length E protein was deleted or its PDZ-binding motif (PBM) was mutated, the revertant viruses either incorporated a novel chimeric protein with a PBM or restored the sequence of the PBM on the E protein, respectively. Similarly, after passage in mice, SARS-CoV-∆E protein 8a mutated, to now encode a PBM, and also regained virulence. These data indicated that the virus requires a PBM on a transmembrane protein to compensate for removal of this motif from the E protein. To increase the genetic stability of the vaccine candidate, we introduced small attenuating deletions in E gene that did not affect the endogenous PBM, preventing the incorporation of novel chimeric proteins in the virus genome. In addition, to increase vaccine biosafety, we introduced additional attenuating mutations into the nsp1 protein. Deletions in the carboxy-terminal region of nsp1 protein led to higher host interferon responses and virus attenuation. Recombinant viruses including attenuating mutations in E and nsp1 genes maintained their attenuation after passage in vitro and in vivo. Further, these viruses fully protected mice against challenge with the lethal parental virus, and are therefore safe and stable vaccine candidates for protection against SARS-CoV.",2015 Oct 29,"['Jimenez-Guardeño, Jose M.', 'Regla-Nava, Jose A.', 'Nieto-Torres, Jose L.', 'DeDiego, Marta L.', 'Castaño-Rodriguez, Carlos', 'Fernandez-Delgado, Raul', 'Perlman, Stanley', 'Enjuanes, Luis']",PLoS Pathog,,,True
67bd507b6486d95e40e4f1435d45efd6421267c9,PMC,Full-Length Genome Characterization of Chinese Porcine Deltacoronavirus Strain CH/SXD1/2015,http://dx.doi.org/10.1128/genomeA.01284-15,PMC4626615,26514769,CC BY,A porcine deltacoronavirus (PDCoV) was identified in the Chinese mainland and found to be closely related to Hong Kong strain HKU15-155 but differed from PDCoV strains in the United States and South Korea. The complete genome of PDCoV strain CH/SXD1/201 was sequenced and analyzed to further characterize PDCoV in Chinese swine.,2015 Oct 29,"['Chen, Fangzhou', 'Zhu, Yinxing', 'Wu, Meizhou', 'Ku, Xugang', 'Yao, Li', 'He, Qigai']",Genome Announc,,,True
0a4f30f5fd02ad89dc9ba18964325c6738807465,PMC,Middle East Respiratory Syndrome and Medical Students: Letter from China,http://dx.doi.org/10.3390/ijerph121013289,PMC4627031,26512679,CC BY,Objectives: The present study aimed to investigate the knowledge of Middle East Respiratory Syndrome (MERS) among Chinese medical students. Methods: A structured questionnaire on MERS was conducted among 214 medical students in China. Results: The average correction of the single question varied from 36.0% to 89.7%. There is a significant difference on MERS knowledge among different majors of medical students (p < 0.05). Management students scored significantly higher than students of other majors (p < 0.05). Conclusion: Chinese medical students had good knowledge of MERS. The MERS knowledge score varied among students of different majors. Education on disease control should be included in the school curriculum.,2015 Oct 23,"['Liu, Mengxue', 'Jiang, Chengsheng', 'Donovan, Connor', 'Wen, Yufeng', 'Wenjie, Sun']",Int J Environ Res Public Health,,,True
053aa0c7280e2bb41a033cb0ae7c0d6bd07afc40,PMC,The role of wobble uridine modifications in +1 translational frameshifting in eukaryotes,http://dx.doi.org/10.1093/nar/gkv832,PMC4627075,26283182,CC BY,"In Saccharomyces cerevisiae, 11 out of 42 tRNA species contain 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U), 5-methoxycarbonylmethyluridine (mcm(5)U), 5-carbamoylmethyluridine (ncm(5)U) or 5-carbamoylmethyl-2′-O-methyluridine (ncm(5)Um) nucleosides in the anticodon at the wobble position (U(34)). Earlier we showed that mutants unable to form the side chain at position 5 (ncm(5) or mcm(5)) or lacking sulphur at position 2 (s(2)) of U(34) result in pleiotropic phenotypes, which are all suppressed by overexpression of hypomodified tRNAs. This observation suggests that the observed phenotypes are due to inefficient reading of cognate codons or an increased frameshifting. The latter may be caused by a ternary complex (aminoacyl-tRNA*eEF1A*GTP) with a modification deficient tRNA inefficiently being accepted to the ribosomal A-site and thereby allowing an increased peptidyl-tRNA slippage and thus a frameshift error. In this study, we have investigated the role of wobble uridine modifications in reading frame maintenance, using either the Renilla/Firefly luciferase bicistronic reporter system or a modified Ty1 frameshifting site in a HIS4A::lacZ reporter system. We here show that the presence of mcm(5) and s(2) side groups at wobble uridines are important for reading frame maintenance and thus the aforementioned mutant phenotypes might partly be due to frameshift errors.",2015 Oct 30,"['Tükenmez, Hasan', 'Xu, Hao', 'Esberg, Anders', 'Byström, Anders S.']",Nucleic Acids Res,,,True
a7106903388d10421825d62d03144d48cc5a3bd9,PMC,The role of wobble uridine modifications in +1 translational frameshifting in eukaryotes,http://dx.doi.org/10.1093/nar/gkv832,PMC4627075,26283182,CC BY,"In Saccharomyces cerevisiae, 11 out of 42 tRNA species contain 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U), 5-methoxycarbonylmethyluridine (mcm(5)U), 5-carbamoylmethyluridine (ncm(5)U) or 5-carbamoylmethyl-2′-O-methyluridine (ncm(5)Um) nucleosides in the anticodon at the wobble position (U(34)). Earlier we showed that mutants unable to form the side chain at position 5 (ncm(5) or mcm(5)) or lacking sulphur at position 2 (s(2)) of U(34) result in pleiotropic phenotypes, which are all suppressed by overexpression of hypomodified tRNAs. This observation suggests that the observed phenotypes are due to inefficient reading of cognate codons or an increased frameshifting. The latter may be caused by a ternary complex (aminoacyl-tRNA*eEF1A*GTP) with a modification deficient tRNA inefficiently being accepted to the ribosomal A-site and thereby allowing an increased peptidyl-tRNA slippage and thus a frameshift error. In this study, we have investigated the role of wobble uridine modifications in reading frame maintenance, using either the Renilla/Firefly luciferase bicistronic reporter system or a modified Ty1 frameshifting site in a HIS4A::lacZ reporter system. We here show that the presence of mcm(5) and s(2) side groups at wobble uridines are important for reading frame maintenance and thus the aforementioned mutant phenotypes might partly be due to frameshift errors.",2015 Oct 30,"['Tükenmez, Hasan', 'Xu, Hao', 'Esberg, Anders', 'Byström, Anders S.']",Nucleic Acids Res,,,False
ec7ab79619e983bb78f09c3b72c0cd36ea2f4924,PMC,Dual Mutation Events in the Haemagglutinin-Esterase and Fusion Protein from an Infectious Salmon Anaemia Virus HPR0 Genotype Promote Viral Fusion and Activation by an Ubiquitous Host Protease,http://dx.doi.org/10.1371/journal.pone.0142020,PMC4627773,26517828,CC BY,"In Infectious salmon anaemia virus (ISAV), deletions in the highly polymorphic region (HPR) in the near membrane domain of the haemagglutinin-esterase (HE) stalk, influence viral fusion. It is suspected that selected mutations in the associated Fusion (F) protein may also be important in regulating fusion activity. To better understand the underlying mechanisms involved in ISAV fusion, several mutated F proteins were generated from the Scottish Nevis and Norwegian SK779/06 HPR0. Co-transfection with constructs encoding HE and F were performed, fusion activity assessed by content mixing assay and the degree of proteolytic cleavage by western blot. Substitutions in Nevis F demonstrated that K276 was the most likely cleavage site in the protein. Furthermore, amino acid substitutions at three sites and two insertions, all slightly upstream of K276, increased fusion activity. Co-expression with HE harbouring a full-length HPR produced high fusion activities when trypsin and low pH were applied. In comparison, under normal culture conditions, groups containing a mutated HE with an HPR deletion were able to generate moderate fusion levels, while those with a full length HPR HE could not induce fusion. This suggested that HPR length may influence how the HE primes the F protein and promotes fusion activation by an ubiquitous host protease and/or facilitate subsequent post-cleavage refolding steps. Variations in fusion activity through accumulated mutations on surface glycoproteins have also been reported in other orthomyxoviruses and paramyxoviruses. This may in part contribute to the different virulence and tissue tropism reported for HPR0 and HPR deleted ISAV genotypes.",2015 Oct 30,"['Fourrier, Mickael', 'Lester, Katherine', 'Markussen, Turhan', 'Falk, Knut', 'Secombes, Christopher J.', 'McBeath, Alastair', 'Collet, Bertrand']",PLoS One,,,True
2a40cae1982703e2b3f357d3721982eef57e0258,PMC,Is There Any Role of Inhalational Corticosteroids in the Prophylaxis of Post-Traumatic Fat Embolism Syndrome?,http://dx.doi.org/10.7759/cureus.332,PMC4627829,26543690,CC BY,"Fat embolism syndrome (FES) is primarily a lung parenchymal disorder resulting from interstitial and alveolar inflammation triggered by the lipid metabolites in blood circulation. The 'low-dose' corticosteroid is supposed to have a prophylactic effect on the incidence of the FES and arterial hypoxemia by reducing this inflammatory response. It is expected that inhaled corticosteroids (ciclesonide aerosol) may prevent the development of hypoxemia or fat embolism syndrome in high-risk patients by reducing this inflammatory response. Metered-dose inhaler (MDI) steroid preparations can reach the lung parenchyma with minimal systemic effect. Sixty cases of polytrauma patients presenting within eight hours of injury were randomly allocated into one of the two groups. In Group 1 (n(1)=30) ciclesonide, 640 mcg, was given with a metered dose inhaler and repeated once again after 24 hours, whereas Group 2 (n(2)=30) was taken as control and observed for 72 hours for any episode of hypoxia. The outcome was assessed using Schonfeld’s criteria for the eventual outcome of subclinical or clinical FES. Out of 30 patients in each group, six patients developed subclinical FES, whereas three from ciclesonide prophylaxis group and eight from controls developed clinical FES. There is no statistical significance found between the eventual outcomes of subclinical or clinical FES between the ciclesonide prophylaxis and control group. Although there was a trend seen in the possible preventive efficacy of inhalational steroid in the present study, it did not reach the statistically significant level. The prophylactic role of inhalational steroid in post-traumatic subclinical and clinical FES is statistically insignificant in the present study.",,"['Agarwal, Amit Kumar', 'Sen, Ramesh', 'Tripathy, Sujit K', 'Aggarwal, Sameer', 'G., Nirmalraj', 'Gupta, Dheeraj']",Cureus.; 7(9):e332,,,True
5a63186e3d015f0bb7378218ebd26b96f7bae63e,PMC,Emergency management training in Korea: combining and balancing supply- and demand-centered paradigms,http://dx.doi.org/10.1186/s40064-015-1459-8,PMC4628130,26543787,CC BY,"This article aims to encourage NEMA (or newly named as MPSS) to combine its supply-centered paradigm with a newly proposed “demand-centered paradigm” in the Korean field of emergency management training (EMT). Based on qualitative content analysis, this paper defined the current field of EMT to be a supply-centered paradigm via three components: locations, courses, and participants. This paradigm focuses on EMT provision as supplied and dictated by the national government. On the other hand, a demand-centered model is about looking into stakeholders’ actual needs for EMT. In this regard, alternatives with reference to the demand-centered paradigm via the same three components were discussed and considered. The key tenet is that having revealed that NEMA has unequivocally focused on the results side or effectiveness of EMT via a supply-centered paradigm, Korea should address and consider the same three components, this time by fusing and incorporating a fair process of EMT by enlisting active roles from the local community, academic scholars, and civilian training attendees in a demand-centered paradigm.",2015 Oct 29,"['Ha, Kyoo-Man', 'Park, Sosoon', 'Yoon, Yi', 'Nam, Ki-Hun', 'Oh, Hyeon-Mun']",Springerplus,,,True
389053111a32e148f8b7c07c883818f70525aa73,PMC,Integrated micro-optofluidic platform for real-time detection of airborne microorganisms,http://dx.doi.org/10.1038/srep15983,PMC4629162,26522006,CC BY,"We demonstrate an integrated micro-optofluidic platform for real-time, continuous detection and quantification of airborne microorganisms. Measurements of the fluorescence and light scattering from single particles in a microfluidic channel are used to determine the total particle number concentration and the microorganism number concentration in real-time. The system performance is examined by evaluating standard particle measurements with various sample flow rates and the ratios of fluorescent to non-fluorescent particles. To apply this method to real-time detection of airborne microorganisms, airborne Escherichia coli, Bacillus subtilis, and Staphylococcus epidermidis cells were introduced into the micro-optofluidic platform via bioaerosol generation, and a liquid-type particle collection setup was used. We demonstrate successful discrimination of SYTO82-dyed fluorescent bacterial cells from other residue particles in a continuous and real-time manner. In comparison with traditional microscopy cell counting and colony culture methods, this micro-optofluidic platform is not only more accurate in terms of the detection efficiency for airborne microorganisms but it also provides additional information on the total particle number concentration.",2015 Nov 2,"['Choi, Jeongan', 'Kang, Miran', 'Jung, Jae Hee']",Sci Rep,,,True
243532558bf1aeed5200836620159cf37f91ab26,PMC,Non-periodic outbreaks of recurrent epidemics and its network modelling,http://dx.doi.org/10.1038/srep16010,PMC4629194,26521709,CC BY,"The study of recurrent epidemic outbreaks has been attracting great attention for decades, but its underlying mechanism is still under debate. Based on a large number of real data from different cities, we find that besides the seasonal periodic outbreaks of influenza, there are also non-periodic outbreaks, i.e. non-seasonal or non-annual behaviors. To understand how the non-periodicity shows up, we present a network model of SIRS epidemic with both time-dependent infection rate and a small possibility of persistent epidemic seeds, representing the influences from the larger annual variation of environment and the infection generated spontaneously in nature, respectively. Our numerical simulations reveal that the model can reproduce the non-periodic outbreaks of recurrent epidemics with the main features of real influenza data. Further, we find that the recurrent outbreaks of epidemic depend not only on the infection rate but also on the density of susceptible agents, indicating that they are both the necessary conditions for the recurrent epidemic patterns with non-periodicity. A theoretical analysis based on Markov dynamics is presented to explain the numerical results. This finding may be of significance to the control of recurrent epidemics.",2015 Nov 2,"['Zheng, Muhua', 'Wang, Chaoqing', 'Zhou, Jie', 'Zhao, Ming', 'Guan, Shuguang', 'Zou, Yong', 'Liu, Zonghua']",Sci Rep,,,True
793d754d6bda1aa545a47999e36e195b64839812,PMC,Non-periodic outbreaks of recurrent epidemics and its network modelling,http://dx.doi.org/10.1038/srep16010,PMC4629194,26521709,CC BY,"The study of recurrent epidemic outbreaks has been attracting great attention for decades, but its underlying mechanism is still under debate. Based on a large number of real data from different cities, we find that besides the seasonal periodic outbreaks of influenza, there are also non-periodic outbreaks, i.e. non-seasonal or non-annual behaviors. To understand how the non-periodicity shows up, we present a network model of SIRS epidemic with both time-dependent infection rate and a small possibility of persistent epidemic seeds, representing the influences from the larger annual variation of environment and the infection generated spontaneously in nature, respectively. Our numerical simulations reveal that the model can reproduce the non-periodic outbreaks of recurrent epidemics with the main features of real influenza data. Further, we find that the recurrent outbreaks of epidemic depend not only on the infection rate but also on the density of susceptible agents, indicating that they are both the necessary conditions for the recurrent epidemic patterns with non-periodicity. A theoretical analysis based on Markov dynamics is presented to explain the numerical results. This finding may be of significance to the control of recurrent epidemics.",2015 Nov 2,"['Zheng, Muhua', 'Wang, Chaoqing', 'Zhou, Jie', 'Zhao, Ming', 'Guan, Shuguang', 'Zou, Yong', 'Liu, Zonghua']",Sci Rep,,,False
055df119df20e08c2830c0b300173e343a760d38,PMC,"Ebola virus disease in the Democratic Republic of the Congo, 1976-2014",http://dx.doi.org/10.7554/eLife.09015,PMC4629279,26525597,CC BY,"The Democratic Republic of the Congo has experienced the most outbreaks of Ebola virus disease since the virus' discovery in 1976. This article provides for the first time a description and a line list for all outbreaks in this country, comprising 996 cases. Compared to patients over 15 years old, the odds of dying were significantly lower in patients aged 5 to 15 and higher in children under five (with 100% mortality in those under 2 years old). The odds of dying increased by 11% per day that a patient was not hospitalised. Outbreaks with an initially high reproduction number, R (>3), were rapidly brought under control, whilst outbreaks with a lower initial R caused longer and generally larger outbreaks. These findings can inform the choice of target age groups for interventions and highlight the importance of both reducing the delay between symptom onset and hospitalisation and rapid national and international response. DOI: http://dx.doi.org/10.7554/eLife.09015.001",,"['Rosello, Alicia', 'Mossoko, Mathias', 'Flasche, Stefan', 'Van Hoek, Albert Jan', 'Mbala, Placide', 'Camacho, Anton', 'Funk, Sebastian', 'Kucharski, Adam', 'Ilunga, Benoit Kebela', 'Edmunds, W John', 'Piot, Peter', 'Baguelin, Marc', 'Muyembe Tamfum, Jean-Jacques']",eLife.; 4:e09015,,,True
4a7c2c60763755a14783f728e9b4cde8bf899f09,PMC,"The role of host genetic factors in respiratory tract infectious diseases: systematic review, meta-analyses and field synopsis",http://dx.doi.org/10.1038/srep16119,PMC4630784,26524966,CC BY,"Host genetic factors have frequently been implicated in respiratory infectious diseases, often with inconsistent results in replication studies. We identified 386 studies from the total of 24,823 studies identified in a systematic search of four bibliographic databases. We performed meta-analyses of studies on tuberculosis, influenza, respiratory syncytial virus, SARS-Coronavirus and pneumonia. One single-nucleotide polymorphism from IL4 gene was significant for pooled respiratory infections (rs2070874; 1.66 [1.29–2.14]). We also detected an association of TLR2 gene with tuberculosis (rs5743708; 3.19 [2.03–5.02]). Subset analyses identified CCL2 as an additional risk factor for tuberculosis (rs1024611; OR = 0.79 [0.72–0.88]). The IL4-TLR2-CCL2 axis could be a highly interesting target for translation towards clinical use. However, this conclusion is based on low credibility of evidence - almost 95% of all identified studies had strong risk of bias or confounding. Future studies must build upon larger-scale collaborations, but also strictly adhere to the highest evidence-based principles in study design, in order to reduce research waste and provide clinically translatable evidence.",2015 Nov 3,"['Patarčić, Inga', 'Gelemanović, Andrea', 'Kirin, Mirna', 'Kolčić, Ivana', 'Theodoratou, Evropi', 'Baillie, Kenneth J.', 'de Jong, Menno D.', 'Rudan, Igor', 'Campbell, Harry', 'Polašek, Ozren']",Sci Rep,,,True
643ce1300f0c4056a709e1b13269a51924960a3a,PMC,Combination effects of ribavirin and interferons on severe fever with thrombocytopenia syndrome virus infection,http://dx.doi.org/10.1186/s12985-015-0412-3,PMC4630909,26527529,CC BY,"BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by SFTS virus and characterized by a high case fatality rate. Currently, there is no effective therapy for the disease. While the administration of ribavirin does not improve the case fatality rate or viral load in patient blood, it can inhibit viral infection in vitro. METHODS: Vero cells were pre-treated with interferons (IFNs) α, β, and γ alone and in combination with ribavirin drugs and inoculated with SFTS virus. Three days later, supernatants were harvested and subjected to virus titration. An unpaired t-test was used for statistical analysis of the drugs’ effects. RESULTS: While the effects of IFNγ at high concentrations were slightly weaker than those of the other IFNs, all IFNs showed dose-dependent inhibitory effects. The combined usage of IFNs with ribavirin at 90 % effective concentrations showed large inhibitory effects, with over a 3 log(10) reduction in viral titers. CONCLUSIONS: The combined usage of one of type-I/II IFNs with ribavirin drastically reduced SFTS virus infection and therefore may be useful in the treatment of SFTS.",2015 Nov 2,"['Shimojima, Masayuki', 'Fukushi, Shuetsu', 'Tani, Hideki', 'Taniguchi, Satoshi', 'Fukuma, Aiko', 'Saijo, Masayuki']",Virol J,,,True
27373ff091fe4a81ee4d6bfc09ece3995080c2ea,PMC,"Proteomic analysis of Pteropus alecto kidney cells in response to the viral mimic, Poly I:C",http://dx.doi.org/10.1186/s12953-015-0081-6,PMC4630911,26535029,CC BY,"BACKGROUND: Bats are recognised as an important reservoir for a number of highly pathogenic zoonotic viruses. While many of these viruses cause severe and often fatal disease in humans, bats are able to coexist with these viruses without clinical signs of disease. The mechanism conferring this antiviral response is not fully understood. Here, we investigated the differential protein expression of immortalised Pteropus alecto kidney cells (PaKiT03) following transfection with the viral mimic, Poly I:C. Two complementary proteomic approaches, difference gel electrophoresis (DIGE) and isobaric tagging for relative and absolute quantitation (iTRAQ) were used to quantify changes in protein expression following Poly I:C stimulation at 4, 8 and 20 hr post treatment (hpt). RESULTS: The expression of ISG54 gene, a known responder to virus infection and Poly I:C treatment, was significantly induced in transfected cells compared with mock-transfected cells. Through iTRAQ analysis we show that Poly I:C up-regulates key glycolytic enzymes at 4 hpt within PaKiT03 cells. In contrast, at 20 hpt PaKiT03 cells down-regulated ribosomal subunit proteins. The analysis with DIGE of Poly I:C transfected PaKiT03 cells showed over 215 individual spots differentially regulated, however only 25 spots could be unambiguously identified by LC-MS/MS. Immunoblotting confirmed the up-regulation of Eno1 and Tpi1 in PaKiT03 cells following Poly I:C transfection. A comparison with human cells (HEK293T and HeLa) and one additional bat cell line (PaLuT02), demonstrated that glycolytic pathways are also induced in these cell types, but at different intensities. CONCLUSION: The two techniques, DIGE and iTRAQ identified largely overlapping sets of differentially expressed proteins, however DIGE unambiguously identified significantly less proteins than iTRAQ. Poly I:C induced a rapid metabolic shift towards glycolysis within the PaKiT03 cells at 4 hpt, presumably as a consequence of increased energy requirements. On the other hand ribosomal subunit proteins were seen as down-regulated by iTRAQ, these proteins may be the limiting factors in the translational machinery available for virus replication. This study provides new insight into the antiviral response of bat cells, highlighting the importance of energy metabolism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12953-015-0081-6) contains supplementary material, which is available to authorized users.",2015 Nov 2,"['Mok, Lawrence', 'Wynne, James W.', 'Ford, Kris', 'Shiell, Brian', 'Bacic, Antony', 'Michalski, Wojtek P.']",Proteome Sci,,,True
0c433c7c4e2e090b2d89d8456f9febed54b71966,PMC,Bat and pig IFN-induced transmembrane protein 3 restrict cell entry by influenza virus and lyssaviruses,http://dx.doi.org/10.1099/vir.0.000058,PMC4631062,25614588,CC BY,"IFN-induced transmembrane protein 3 (IFITM3) is a restriction factor that blocks cytosolic entry of numerous viruses that utilize acidic endosomal entry pathways. In humans and mice, IFITM3 limits influenza-induced morbidity and mortality. Although many IFITM3-sensitive viruses are zoonotic, whether IFITMs function as antiviral restriction factors in mammalian species other than humans and mice is unknown. Here, IFITM3 orthologues in the microbat (Myotis myotis) and pig (Sus scrofa domesticus) were identified using rapid amplification of cDNA ends. Amino acid residues known to be important for IFITM3 function were conserved in the pig and microbat orthologues. Ectopically expressed pig and microbat IFITM3 co-localized with transferrin (early endosomes) and CD63 (late endosomes/multivesicular bodies). Pig and microbat IFITM3 restricted cell entry mediated by multiple influenza haemagglutinin subtypes and lyssavirus glycoproteins. Expression of pig or microbat IFITM3 in A549 cells reduced influenza virus yields and nucleoprotein expression. Conversely, small interfering RNA knockdown of IFITM3 in pig NPTr cells and primary microbat cells enhanced virus replication, demonstrating that these genes are functional in their species of origin at endogenous levels. In summary, we showed that IFITMs function as potent broad-spectrum antiviral effectors in two mammals – pigs and bats – identified as major reservoirs for emerging viruses.",2015 May,"['Benfield, Camilla T. O.', 'Smith, Sarah E.', 'Wright, Edward', 'Wash, Rachael S.', 'Ferrara, Francesca', 'Temperton, Nigel J.', 'Kellam, Paul']",J Gen Virol,,,True
51a7b35db673f0d7cb14a80b607192e3f44cc7f5,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,True
92b94c1462d7b041b4384427330fb96356a460d3,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
6d2d02b0a6ecb9c3b18b5493a915c98aef617c4c,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
dbc083ba64144327640e834733ed3bdd22547ac1,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
efe3c8971043fad4fc42ab12968b8c281ab51993,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
94aa6c926b7d24d310c5e1f69e855a4cf2629a47,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
2c5f2f209d53eb9970b4e4af47eb142bcb439af1,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
7ba894b5e65044ba373e4a09430c3dc4c069bbab,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
d4dd5cbb2f849bfaf7aeff57858e8cf5429d4698,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
d053a0f318f0d42cf1c06dabf67e94e944ec7da4,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
48daab48d460ec33f5f8263bd5ac7aa866490e48,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
239ca8536007960c7aed8369da414b93702217f2,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,False
ed468ccf95499f1d19c071accb82a8bc64696ace,PMC,Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis,http://dx.doi.org/10.1371/journal.pmed.1001898,PMC4631366,26529093,CC BY,"BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.",2015 Nov 3,"['Bezemer, Daniela', 'Cori, Anne', 'Ratmann, Oliver', 'van Sighem, Ard', 'Hermanides, Hillegonda S.', 'Dutilh, Bas E.', 'Gras, Luuk', 'Rodrigues Faria, Nuno', 'van den Hengel, Rob', 'Duits, Ashley J.', 'Reiss, Peter', 'de Wolf, Frank', 'Fraser, Christophe', None]",PLoS Med,,,True
55b2f19377928da52d9826a5de0714e5c75ebd02,PMC,The Effects of Media Reports on Disease Spread and Important Public Health Measurements,http://dx.doi.org/10.1371/journal.pone.0141423,PMC4631512,26528909,CC BY,"Controlling the spread of influenza to reduce the effects of infection on a population is an important mandate of public health. Mass media reports on an epidemic or pandemic can provide important information to the public, and in turn, can induce positive healthy behaviour practices (i.e., handwashing, social distancing) in the individuals, that will reduce the probability of contracting the disease. Mass media fatigue, however, can dampen these effects. Mathematical models can be used to study the effects of mass media reports on epidemic/pandemic outcomes. In this study we employ a stochastic agent based model to provide a quantification of mass media reports on the variability in important public health measurements. We also include mass media report data compiled by the Global Public Health Intelligence Network, to study the effects of mass media reports in the 2009 H1N1 pandemic. We find that the report rate and the rate at which individuals relax their healthy behaviours (media fatigue) greatly affect the variability in important public health measurements. When the mass media reporting data is included in the model, two peaks of infection result.",2015 Nov 3,"['Collinson, Shannon', 'Khan, Kamran', 'Heffernan, Jane M.']",PLoS One,,,True
c9b76a5f0e49ab1510fa1161baf7d588656582f6,PMC,Viroporins: Structures and Functions beyond Cell Membrane Permeabilization,http://dx.doi.org/10.3390/v7102866,PMC4632374,26702461,CC BY,,2015 Sep 29,"['Nieva, José Luis', 'Carrasco, Luis']",Viruses,,,True
75e5e406f83b2f0a94abc8cbed71cbb900f9956e,PMC,The Role of Electron Microscopy in Studying the Continuum of Changes in Membranous Structures during Poliovirus Infection,http://dx.doi.org/10.3390/v7102874,PMC4632382,26473912,CC BY,"Replication of the poliovirus genome is localized to cytoplasmic replication factories that are fashioned out of a mixture of viral proteins, scavenged cellular components, and new components that are synthesized within the cell due to viral manipulation/up-regulation of protein and phospholipid synthesis. These membranous replication factories are quite complex, and include markers from multiple cytoplasmic cellular organelles. This review focuses on the role of electron microscopy in advancing our understanding of poliovirus RNA replication factories. Structural data from the literature provide the basis for interpreting a wide range of biochemical studies that have been published on virus-induced lipid biosynthesis. In combination, structural and biochemical experiments elucidate the dramatic membrane remodeling that is a hallmark of poliovirus infection. Temporal and spatial membrane modifications throughout the infection cycle are discussed. Early electron microscopy studies of morphological changes following viral infection are re-considered in light of more recent data on viral manipulation of lipid and protein biosynthesis. These data suggest the existence of distinct subcellular vesicle populations, each of which serves specialized roles in poliovirus replication processes.",2015 Oct 12,"['Rossignol, Evan D.', 'Yang, Jie E.', 'Bullitt, Esther']",Viruses,,,True
a599eb2c6ca51522fa234d8059f989569f4fe298,PMC,Emerging Roles of Viroporins Encoded by DNA Viruses: Novel Targets for Antivirals?,http://dx.doi.org/10.3390/v7102880,PMC4632388,26501313,CC BY,"Studies have highlighted the essential nature of a group of small, highly hydrophobic, membrane embedded, channel-forming proteins in the life cycles of a growing number of RNA viruses. These viroporins mediate the flow of ions and a range of solutes across cellular membranes and are necessary for manipulating a myriad of host processes. As such they contribute to all stages of the virus life cycle. Recent discoveries have identified proteins encoded by the small DNA tumor viruses that display a number of viroporin like properties. This review article summarizes the recent developments in our understanding of these novel viroporins; describes their roles in the virus life cycles and in pathogenesis and speculates on their potential as targets for anti-viral therapeutic intervention.",2015 Oct 16,"['Royle, Jamie', 'Dobson, Samuel John', 'Müller, Marietta', 'Macdonald, Andrew']",Viruses,,,True
f6a6f1fcc991eaf6e733d88adb25a3a7a8e65546,PMC,Sequence and Structure Analysis of Distantly-Related Viruses Reveals Extensive Gene Transfer between Viruses and Hosts and among Viruses,http://dx.doi.org/10.3390/v7102882,PMC4632390,26492264,CC BY,"The origin and evolution of viruses is a subject of ongoing debate. In this study, we provide a full account of the evolutionary relationships between proteins of significant sequence and structural similarity found in viruses that belong to different classes according to the Baltimore classification. We show that such proteins can be found in viruses from all Baltimore classes. For protein families that include these proteins, we observe two patterns of the taxonomic spread. In the first pattern, they can be found in a large number of viruses from all implicated Baltimore classes. In the other pattern, the instances of the corresponding protein in species from each Baltimore class are restricted to a few compact clades. Proteins with the first pattern of distribution are products of so-called viral hallmark genes reported previously. Additionally, this pattern is displayed by the envelope glycoproteins from Flaviviridae and Bunyaviridae and helicases of superfamilies 1 and 2 that have homologs in cellular organisms. The second pattern can often be explained by horizontal gene transfer from the host or between viruses, an example being Orthomyxoviridae and Coronaviridae hemagglutinin esterases. Another facet of horizontal gene transfer comprises multiple independent introduction events of genes from cellular organisms into otherwise unrelated viruses.",2015 Oct 19,"['Caprari, Silvia', 'Metzler, Saskia', 'Lengauer, Thomas', 'Kalinina, Olga V.']",Viruses,,,True
8f44e4d806117b957383a7ee870d2dd38213f094,PMC,Perspective of Use of Antiviral Peptides against Influenza Virus,http://dx.doi.org/10.3390/v7102883,PMC4632391,26492266,CC BY,"The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20(th) century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides.",2015 Oct 20,"['Skalickova, Sylvie', 'Heger, Zbynek', 'Krejcova, Ludmila', 'Pekarik, Vladimir', 'Bastl, Karel', 'Janda, Jozef', 'Kostolansky, Frantisek', 'Vareckova, Eva', 'Zitka, Ondrej', 'Adam, Vojtech', 'Kizek, Rene']",Viruses,,,True
578ad49441884c636eb9d6044237708eb6437afb,PMC,Complete Genome and Phylogeny of Puumala Hantavirus Isolates Circulating in France,http://dx.doi.org/10.3390/v7102884,PMC4632392,26506370,CC BY,"Puumala virus (PUUV) is the agent of nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) in Europe. NE incidence presents a high spatial variation throughout France, while the geographical distribution of the wild reservoir of PUUV, the bank vole, is rather continuous. A missing piece of the puzzle is the current distribution and the genetic variation of PUUV in France, which has been overlooked until now and remains poorly understood. During a population survey, from 2008 to 2011, bank voles were trapped in eight different forests of France located in areas known to be endemic for NE or in area from where no NE case has been reported until now. Bank voles were tested for immunoglobulin (Ig)G ELISA serology and two seropositive animals for each of three different areas (Ardennes, Jura and Orleans) were then subjected to laboratory analyses in order to sequence the whole S, M and L segments of PUUV. Phylogenetic analyses revealed that French PUUV isolates globally belong to the central European (CE) lineage although isolates from Ardennes are clearly distinct from those in Jura and Orleans, suggesting a different evolutionary history and origin of PUUV introduction in France. Sequence analyses revealed specific amino acid signatures along the N protein, including in PUUV from the Orleans region from where NE in humans has never been reported. The relevance of these mutations in term of pathophysiology is discussed.",2015 Oct 22,"['Castel, Guillaume', 'Couteaudier, Mathilde', 'Sauvage, Frank', 'Pons, Jean-Baptiste', 'Murri, Séverine', 'Plyusnina, Angelina', 'Pontier, Dominique', 'Cosson, Jean-François', 'Plyusnin, Alexander', 'Marianneau, Philippe', 'Tordo, Noël']",Viruses,,,True
3e3097dd0c6d06cce3de6c065c6558807d12ae7e,PMC,Complete Genome and Phylogeny of Puumala Hantavirus Isolates Circulating in France,http://dx.doi.org/10.3390/v7102884,PMC4632392,26506370,CC BY,"Puumala virus (PUUV) is the agent of nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) in Europe. NE incidence presents a high spatial variation throughout France, while the geographical distribution of the wild reservoir of PUUV, the bank vole, is rather continuous. A missing piece of the puzzle is the current distribution and the genetic variation of PUUV in France, which has been overlooked until now and remains poorly understood. During a population survey, from 2008 to 2011, bank voles were trapped in eight different forests of France located in areas known to be endemic for NE or in area from where no NE case has been reported until now. Bank voles were tested for immunoglobulin (Ig)G ELISA serology and two seropositive animals for each of three different areas (Ardennes, Jura and Orleans) were then subjected to laboratory analyses in order to sequence the whole S, M and L segments of PUUV. Phylogenetic analyses revealed that French PUUV isolates globally belong to the central European (CE) lineage although isolates from Ardennes are clearly distinct from those in Jura and Orleans, suggesting a different evolutionary history and origin of PUUV introduction in France. Sequence analyses revealed specific amino acid signatures along the N protein, including in PUUV from the Orleans region from where NE in humans has never been reported. The relevance of these mutations in term of pathophysiology is discussed.",2015 Oct 22,"['Castel, Guillaume', 'Couteaudier, Mathilde', 'Sauvage, Frank', 'Pons, Jean-Baptiste', 'Murri, Séverine', 'Plyusnina, Angelina', 'Pontier, Dominique', 'Cosson, Jean-François', 'Plyusnin, Alexander', 'Marianneau, Philippe', 'Tordo, Noël']",Viruses,,,False
bfe634ff1fa0e8f0a43c1bd5fa6e0b5bd17705ee,PMC,Comparative Genomic Analysis of Classical and Variant Virulent Parental/Attenuated Strains of Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.3390/v7102891,PMC4632399,26512689,CC BY,"Since 2010, the variant porcine epidemic diarrhea virus (PEDV) has been the etiological agent responsible for the outbreak of porcine epidemic diarrhea (PED) worldwide. In this study, a variant PEDV strain YN1 was isolated, serially propagated on the Vero cells and was characterized for 200 passages. To better elucidate the molecular basis of Vero cell adaptation of variant PEDV strains, we sequenced, compared, and analyzed the full-genome sequences of parental YN1 and passages 15, 30, 60, 90, 144, and 200. The results showed that the variations increased with the viral passage. The nucleotides sequences of non-structural protein (NSP)2, NSP4-7, NSP10, NSP12 and NSP13 genes did not change during the Vero cell adaptation process. After comparison of the variation characteristic of classical, variant virulent/attenuated strains, it was found that attenuation of PEDV virus was associated with 9−26 amino acid (aa) changes in open reading frames (ORF) 1a/b and S protein, early termination in ORF3, 1–3 aa changes in E, M and N protein and some nucleotide sequences’ synonymous mutations. The aa deletion at about 144 aa of S protein could be the attenuation marker for the PEDV. The pig study showed that the early termination in ORF3 was more important for virus cell adaptation than virus attenuation.",2015 Oct 23,"['Chen, Fangzhou', 'Zhu, Yinxing', 'Wu, Meizhou', 'Ku, Xugang', 'Ye, Shiyi', 'Li, Zhonghua', 'Guo, Xiaozhen', 'He, Qigai']",Viruses,,,True
060833389f07819960d34c91e0dfdc92e053f6ac,PMC,Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2,http://dx.doi.org/10.3390/v7102893,PMC4632401,26512690,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) infection strongly modulates the host’s immune response. The RNA silencing pathway is an intracellular innate response to viral infections. However, it is unknown whether PRRSV interacts with cellular RNA silencing to facilitate the viral infection. Here, we report for the first time the interaction between PRRSV and RNA silencing in both the porcine macrophages and African green monkey kidney cell line (MARC-145) cell line, which were derived from African green monkey kidney cells and highly permissive for PRRSV infection. Our data demonstrated that PRRSV suppressed RNA silencing induced by short-hairpin (sh) RNA, double-strand (ds) RNA and microRNA (miRNA) and downregulated the expression of argonaute protein-2 (Ago-2), which is a key protein of the RNA silencing pathway in animal cells. Further, exogenous introduction of siRNA and shRNA downregulated Dicer or Ago-2 proteins of the cellular RNA silencing apparatus in MARC-145 cells and porcine macrophages, which, in turn, increased the viral replication and titers. The viral non-structure protein 1α (nsp-1α) and nsp11 of PRRSV were identified as the suppressors for cellular RNA silencing (RSSs) to downregulate the Ago-2 protein. Our results identify that PRRSV, through its nsp proteins, suppresses the cellular RNA silencing apparatus in favor of viral infection and supports a co-evolutionary process of the virus and the cellular RNA silencing process.",2015 Oct 23,"['Chen, Jing', 'Shi, Xibao', 'Zhang, Xiaozhuan', 'Wang, Li', 'Luo, Jun', 'Xing, Guangxu', 'Deng, Ruiguang', 'Yang, Hong', 'Li, Jinting', 'Wang, Aiping', 'Zhang, Gaiping']",Viruses,,,True
57599ec2644e90c8c79737ed565edb7d6b286fc5,PMC,Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase,http://dx.doi.org/10.3390/v7102894,PMC4632402,26516899,CC BY,"The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I) in the RNA-dependent RNA polymerase (RdRp). We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding this variant are attenuated in a mouse model of poliovirus. Given these results, it was surprising that the nucleotide incorporation rate and nucleobase fidelity of the Sabin I RdRp is similar to that of wild-type enzyme, although the Sabin I RdRp is less selective against nucleotides with modified sugar groups. We suggest that the other Sabin amino acid changes (i.e., D53N, Y73H, K250E) help to re-establish nucleotide incorporation rates and nucleotide discrimination near wild-type levels, which may be a requirement for the propagation of the virus and its efficacy as a vaccine strain. These results also suggest that the nucleobase fidelity of the Sabin I RdRp likely does not contribute to viral attenuation.",2015 Oct 26,"['Liu, Xinran', 'Musser, Derek M.', 'Lee, Cheri A.', 'Yang, Xiaorong', 'Arnold, Jamie J.', 'Cameron, Craig E.', 'Boehr, David D.']",Viruses,,,True
0706374e8a8a5eaf3bff4d2555c0f0db11294755,PMC,The Ethanol Extract from Lonicera japonica Thunb. Regresses Nonalcoholic Steatohepatitis in a Methionine- and Choline-Deficient Diet-Fed Animal Model,http://dx.doi.org/10.3390/nu7105423,PMC4632443,26506376,CC BY,"Nonalcoholic steatohepatitis (NASH) is characterized as fat accumulation in the hepatic tissue associated with various degrees of inflammation and progressive fibrosis. The potent anti-inflammatory and ethnopharmacological properties of Lonicera japonica Thunb. (Caprifoliaceae) make it an excellent source of novel medicinal targets for the treatment of NASH. The aim of the study was to investigate the effects of L. japonica ethanol extract (LJEE) on NASH in mice. C57BL/6J mice were fed with methionine-choline-deficient diet (MCDD) for eight weeks to promote the development of NASH. After development of the model, the mice were administered LJEE once daily via oral gavage at doses of 100, 200, or 300 mg/kg for another four weeks. Simultaneous treatments with LJEE (300 mg/kg/day) resulted in pronounced improvements in liver steatosis, ballooning degeneration, and inflammation. LJEE prevented MCDD-induced plasma level increases in aspartate aminotransferase and alanine aminotransferase. LJEE significantly reduced hepatic malondialdehyde level and ameliorated hepatic inflammation and fibrosis in MCDD-fed mice, which were associated with down-regulation of cytochrome P450 2E1 suppression of multiple proinflammatory and profibrotic genes. LJEE can prevent hepatic steatosis by reducing hepatic peroxisome acyl-CoA:diacylglycerol acyltransferase 2 expression, as well as by inducing proliferator-activated receptor α expression. In addition, the LJEE treatments caused significant reduction in the phosphorylated form of Jun N-terminal kinase along with an increase in the phosphorylated level of extra cellular signal-regulated kinase 1/2. Our study demonstrated the protective role of LJEE in ameliorating nutritional steatohepatitis.",2015 Oct 21,"['Tzeng, Thing-Fong', 'Tzeng, Yu-Cheng', 'Cheng, Yu-Jou', 'Liou, Shorong-Shii', 'Liu, I-Min']",Nutrients,,,True
71f45bcdac8e83e02ee1d8b5eab8ce5c425f5cce,PMC,Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins,http://dx.doi.org/10.3390/molecules20034610,PMC4633014,25774492,CC BY,"Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA), for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV), and human cytomegalovirus (HCMV). In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man(9)GlcNAc(2)Asn (Man9)-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn). These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation.",2015 Mar 12,"['Wang, Denong', 'Tang, Jin', 'Tang, Jiulai', 'Wang, Lai-Xi']",Molecules,,,True
07330c35eb8beda0a4b515b8a0edce5d42662417,PMC,Detection of a novel astrovirus from a black-naped monarch (Hypothymis azurea) in Cambodia,http://dx.doi.org/10.1186/s12985-015-0413-2,PMC4634723,26537007,CC BY,"BACKGROUND: Astroviruses are comprised of two genera with Avastrovirus infecting birds and Mamastrovirus infecting mammals. Avastroviruses have primarily been associated with infections of poultry, especially chicken, turkey, duck, and guineafowl production systems, but also infect wading birds and doves. Outcomes result in a spectrum of disease, ranging from asymptomatic shedding to gastroenteritis with diarrhea, stunting, failure to thrive and death. FINDINGS: Virological surveillance was conducted in birds from two sites in Cambodia in 2010. Samples were screened for influenza, astroviruses, coronaviruses, flaviviruses, and paramyxoviruses. A total of 199 birds were tested and an astrovirus was detected in a black-naped monarch (Hypothymis azurea). CONCLUSIONS: This is the first astrovirus detection in a passerine bird. Phylogenetic analysis and nucleotide distances suggest that this avastrovirus forms a distinct lineage and may constitute a fourth avastrovirus group. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0413-2) contains supplementary material, which is available to authorized users.",2015 Nov 4,"['Mendenhall, Ian H.', 'Yaung, Katherine Nay', 'Joyner, Priscilla H.', 'Keatts, Lucy', 'Borthwick, Sophie', 'Neves, Erica Sena', 'San, Sorn', 'Gilbert, Martin', 'Smith, Gavin JD']",Virol J,,,True
8e7d05c2e304aa0430befd8259b9bb6c863a0f29,PMC,Detection of a novel astrovirus from a black-naped monarch (Hypothymis azurea) in Cambodia,http://dx.doi.org/10.1186/s12985-015-0413-2,PMC4634723,26537007,CC BY,"BACKGROUND: Astroviruses are comprised of two genera with Avastrovirus infecting birds and Mamastrovirus infecting mammals. Avastroviruses have primarily been associated with infections of poultry, especially chicken, turkey, duck, and guineafowl production systems, but also infect wading birds and doves. Outcomes result in a spectrum of disease, ranging from asymptomatic shedding to gastroenteritis with diarrhea, stunting, failure to thrive and death. FINDINGS: Virological surveillance was conducted in birds from two sites in Cambodia in 2010. Samples were screened for influenza, astroviruses, coronaviruses, flaviviruses, and paramyxoviruses. A total of 199 birds were tested and an astrovirus was detected in a black-naped monarch (Hypothymis azurea). CONCLUSIONS: This is the first astrovirus detection in a passerine bird. Phylogenetic analysis and nucleotide distances suggest that this avastrovirus forms a distinct lineage and may constitute a fourth avastrovirus group. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0413-2) contains supplementary material, which is available to authorized users.",2015 Nov 4,"['Mendenhall, Ian H.', 'Yaung, Katherine Nay', 'Joyner, Priscilla H.', 'Keatts, Lucy', 'Borthwick, Sophie', 'Neves, Erica Sena', 'San, Sorn', 'Gilbert, Martin', 'Smith, Gavin JD']",Virol J,,,True
136f5dd69cd65fb0826ded4d9f51af7969dfcbcd,PMC,Suppression subtractive hybridization method for the identification of a new strain of murine hepatitis virus from xenografted SCID mice,http://dx.doi.org/10.1007/s00705-015-2592-y,PMC4635179,26347284,CC BY,"During attempts to clone retroviral determinants associated with a mouse model of Langerhans cell histiocytosis (LCH), suppression subtractive hybridization (SSH) was used to identify unique viruses in the liver of severe combined immunodeficiency (SCID) mice transplanted with LCH tissues. A partial genomic sequence of a murine coronavirus was identified, and the whole genome (31428 bp) of the coronavirus was subsequently sequenced using PCR cloning techniques. Nucleotide sequence comparisons revealed that the genome sequence of the new virus was 91-93 % identical to those of known murine hepatitis viruses (MHVs). The predicted open reading frame from the nucleotide sequence encoded all known proteins of MHVs. Analysis at the protein level showed that the virus was closely related to the highly virulent MHV-JHM strain. The virus strain was named MHV-MI. No type D retroviruses were found. Degenerate PCR targeting of type D retrovirus and 5′-RACE targeting of other types of retroviruses confirmed the absence of any retroviral association with the LCH xenografted SCID mice.",2015 Sep 8,"['Islam, Mohammed M.', 'Toohey, Brendan', 'Purcell, Damian F. J.', 'Kannourakis, George']",Arch Virol,,,True
d85ef5950a1be68a4dd4eebed557563bf88ba8ff,PMC,Genotyping coronaviruses associated with feline infectious peritonitis,http://dx.doi.org/10.1099/vir.0.000084,PMC4635486,25667330,CC BY,"Feline coronavirus (FCoV) infections are endemic among cats worldwide. The majority of infections are asymptomatic or result in only mild enteric disease. However, approximately 5 % of cases develop feline infectious peritonitis (FIP), a systemic disease that is a frequent cause of death in young cats. In this study, we report the complete coding genome sequences of six FCoVs: three from faecal samples from healthy cats and three from tissue lesion samples from cats with confirmed FIP. The six samples were obtained over a period of 8 weeks at a single-site cat rescue and rehoming centre in the UK. We found amino acid differences located at 44 positions across an alignment of the six virus translatomes and, at 21 of these positions, the differences fully or partially discriminated between the genomes derived from the faecal samples and the genomes derived from the tissue lesion samples. In this study, two amino acid differences fully discriminated the two classes of genomes: these were both located in the S2 domain of the virus surface glycoprotein gene. We also identified deletions in the 3c protein ORF of genomes from two of the FIP samples. Our results support previous studies that implicate S protein mutations in the pathogenesis of FIP.",2015 Jun,"['Lewis, Catherine S.', 'Porter, Emily', 'Matthews, David', 'Kipar, Anja', 'Tasker, Séverine', 'Helps, Christopher R.', 'Siddell, Stuart G.']",J Gen Virol,,,True
b9795ebc63bc667ed27545d63f287cacf8604d62,PMC,Discovery of a polyomavirus in European badgers (Meles meles) and the evolution of host range in the family Polyomaviridae,http://dx.doi.org/10.1099/vir.0.000071,PMC4635489,25626684,CC BY,"Polyomaviruses infect a diverse range of mammalian and avian hosts, and are associated with a variety of symptoms. However, it is unknown whether the viruses are found in all mammalian families and the evolutionary history of the polyomaviruses is still unclear. Here, we report the discovery of a novel polyomavirus in the European badger (Meles meles), which to our knowledge represents the first polyomavirus to be characterized in the family Mustelidae, and within a European carnivoran. Although the virus was discovered serendipitously in the supernatant of a cell culture inoculated with badger material, we subsequently confirmed its presence in wild badgers. The European badger polyomavirus was tentatively named Meles meles polyomavirus 1 (MmelPyV1). The genome is 5187 bp long and encodes proteins typical of polyomaviruses. Phylogenetic analyses including all known polyomavirus genomes consistently group MmelPyV1 with California sea lion polyomavirus 1 across all regions of the genome. Further evolutionary analyses revealed phylogenetic discordance amongst polyomavirus genome regions, possibly arising from evolutionary rate heterogeneity, and a complex association between polyomavirus phylogeny and host taxonomic groups.",2015 Jun,"['Hill, Sarah C.', 'Murphy, Aisling A.', 'Cotten, Matthew', 'Palser, Anne L.', 'Benson, Phillip', 'Lesellier, Sandrine', 'Gormley, Eamonn', 'Richomme, Céline', 'Grierson, Sylvia', 'Bhuachalla, Deirdre Ni', 'Chambers, Mark', 'Kellam, Paul', 'Boschiroli, María-Laura', 'Ehlers, Bernhard', 'Jarvis, Michael A.', 'Pybus, Oliver G.']",J Gen Virol,,,True
ef6361c7bffb9e92f397d7004bfb3a9c804d7c6a,PMC,"Viral Respiratory Tract Infections in Adult Patients Attending Outpatient and Emergency Departments, Taiwan, 2012–2013: A PCR/Electrospray Ionization Mass Spectrometry Study",http://dx.doi.org/10.1097/MD.0000000000001545,PMC4635751,26402811,CC BY,"Viral etiologies of respiratory tract infections (RTIs) have been less studied in adult than in pediatric populations. Furthermore, the ability of PCR/electrospray ionization mass spectrometry (PCR/ESI-MS) to detect enteroviruses and rhinoviruses in respiratory samples has not been well evaluated. We sought to use PCR/ESI-MS to comprehensively investigate the viral epidemiology of adult RTIs, including testing for rhinoviruses and enteroviruses. Nasopharyngeal or throat swabs from 267 adults with acute RTIs (212 upper RTIs and 55 lower RTIs) who visited a local clinic or the outpatient or emergency departments of a medical center in Taiwan between October 2012 and June 2013 were tested for respiratory viruses by both virus isolation and PCR/ESI-MS. Throat swabs from 15 patients with bacterial infections and 27 individuals without active infections were included as control samples. Respiratory viruses were found in 23.6%, 47.2%, and 47.9% of the 267 cases by virus isolation, PCR/ESI-MS, and both methods, respectively. When both methods were used, the influenza A virus (24.3%) and rhinoviruses (9.4%) were the most frequently identified viruses, whereas human coronaviruses, human metapneumovirus (hMPV), enteroviruses, adenoviruses, respiratory syncytial virus, and parainfluenza viruses were identified in small proportions of cases (<5% of cases for each type of virus). Coinfection was observed in 4.1% of cases. In the control group, only 1 (2.4%) sample tested positive for a respiratory virus by PCR/ESI-MS. Patients who were undergoing steroid treatment, had an active malignancy, or suffered from chronic obstructive pulmonary disease (COPD) were at risk for rhinovirus, hMPV, or parainfluenza infections, respectively. Overall, immunocompromised patients, patients with COPD, and patients receiving dialysis were at risk for noninfluenza respiratory virus infection. Rhinoviruses (12.7%), influenza A virus (10.9%), and parainfluenza viruses (7.3%) were the most common viruses involved in the 55 cases of lower RTIs. The factors of parainfluenza infection, old age, and immunosuppression were independently associated with lower RTIs. In conclusion, PCR/ESI-MS improved the diagnostic yield for viral RTIs. Non-influenza respiratory virus infections were associated with patients with comorbidities and with lower RTIs. Additional studies that delineate the clinical need for including non-influenza respiratory viruses in the diagnostic work-up in these populations are warranted.",2015 Sep 25,"['Shih, Hsin-I', 'Wang, Hsuan-Chen', 'Su, Ih-Jen', 'Hsu, Hsiang-Chin', 'Wang, Jen-Ren', 'Sun, Hsiao Fang Sunny', 'Chou, Chien-Hsuan', 'Ko, Wen-Chien', 'Hsieh, Ming-I', 'Wu, Chi-Jung']",Medicine (Baltimore),,,True
dacc557b6e40bb69974e2e1a831aef665e524867,PMC,Cleavage of a Neuroinvasive Human Respiratory Virus Spike Glycoprotein by Proprotein Convertases Modulates Neurovirulence and Virus Spread within the Central Nervous System,http://dx.doi.org/10.1371/journal.ppat.1005261,PMC4636366,26545254,CC BY,"Human coronaviruses (HCoV) are respiratory pathogens that may be associated with the development of neurological diseases, in view of their neuroinvasive and neurotropic properties. The viral spike (S) glycoprotein is a major virulence factor for several coronavirus species, including the OC43 strain of HCoV (HCoV-OC43). In an attempt to study the role of this protein in virus spread within the central nervous system (CNS) and neurovirulence, as well as to identify amino acid residues important for such functions, we compared the sequence of the S gene found in the laboratory reference strain HCoV-OC43 ATCC VR-759 to S sequences of viruses detected in clinical isolates from the human respiratory tract. We identified one predominant mutation at amino acid 758 (from RRSR↓ G (758) to RRSR↓R (758)), which introduces a putative furin-like cleavage (↓) site. Using a molecular cDNA infectious clone to generate a corresponding recombinant virus, we show for the first time that such point mutation in the HCoV-OC43 S glycoprotein creates a functional cleavage site between the S1 and S2 portions of the S protein. While the corresponding recombinant virus retained its neuroinvasive properties, this mutation led to decreased neurovirulence while potentially modifying the mode of virus spread, likely leading to a limited dissemination within the CNS. Taken together, these results are consistent with the adaptation of HCoV-OC43 to the CNS environment, resulting from the selection of quasi-species harboring mutations that lead to amino acid changes in viral genes, like the S gene in HCoV-OC43, which may contribute to a more efficient establishment of a less pathogenic but persistent CNS infection. This adaptative mechanism could potentially be associated with human encephalitis or other neurological degenerative pathologies.",2015 Nov 6,"['Le Coupanec, Alain', 'Desforges, Marc', 'Meessen-Pinard, Mathieu', 'Dubé, Mathieu', 'Day, Robert', 'Seidah, Nabil G.', 'Talbot, Pierre J.']",PLoS Pathog,,,True
696ae2cd59982a2cb456ed723adb98586ebdf7f7,PMC,Ultrasensitive Detection of RNA and DNA Viruses Simultaneously Using Duplex UNDP-PCR Assay,http://dx.doi.org/10.1371/journal.pone.0141545,PMC4636378,26544710,CC BY,"Mixed infection of multiple viruses is common in modern intensive pig rearing. However, there are no methods available to detect DNA and RNA viruses in the same reaction system in preclinical level. In this study, we aimed to develop a duplex ultrasensitive nanoparticle DNA probe-based PCR assay (duplex UNDP-PCR) that was able to simultaneously detect DNA and RNA viruses in the same reaction system. PCV2 and TGEV are selected as representatives of the two different types of viruses. PCV2 DNA and TGEV RNA were simultaneously released from the serum sample by boiling with lysis buffer, then magnetic beads and gold nanoparticles coated with single and/or duplex specific probes for TGEV and PCV2 were added to form a sandwich-like complex with nucleic acids released from viruses. After magnetic separation, DNA barcodes specific for PCV2 and TGEV were eluted using DTT and characterized by specific PCR assay for specific DNA barcodes subsequently. The duplex UNDP-PCR showed similar sensitivity as that of single UNDP-PCR and was able to detect 20 copies each of PCV2 and TGEV in the serum, showing approximately 250-fold more sensitivity than conventional duplex PCR/RT-PCR assays. No cross-reaction was observed with other viruses. The positive detection rate of single MMPs- and duplex MMPs-based duplex UNDP-PCR was identical, with 29.6% for PCV2, 9.3% for TGEV and 3.7% for PCV2 and TGEV mixed infection. This duplex UNDP-PCR assay could detect TGEV (RNA virus) and PCV2 (DNA virus) from large-scale serum samples simultaneously without the need for DNA/RNA extraction, purification and reverse transcription of RNA, and showed a significantly increased positive detection rate for PCV2 (29%) and TGEV (11.7%) preclinical infection than conventional duplex PCR/RT-PCR. Therefore, the established duplex UNDP-PCR is a rapid and economical detection method, exhibiting high sensitivity, specificity and reproducibility.",2015 Nov 6,"['Huang, Yong', 'Xing, Na', 'Wang, Zengguo', 'Zhang, Xiujuan', 'Zhao, Xiaomin', 'Du, Qian', 'Chang, Lingling', 'Tong, Dewen']",PLoS One,,,True
543819a7a29de2c78dd6e147beed7be72466c610,PMC,Capacity building in national influenza laboratories – use of laboratory assessments to drive progress,http://dx.doi.org/10.1186/s12879-015-1232-1,PMC4636816,26546333,CC BY,"BACKGROUND: Laboratory testing is a fundamental component of influenza surveillance for detecting novel strains with pandemic potential and informing biannual vaccine strain selection. The United States (U.S.) Centers for Disease Control and Prevention (CDC), under the auspices of its WHO Collaborating Center for Influenza, is one of the major public health agencies which provides support globally to build national capacity for influenza surveillance. Our main objective was to determine if laboratory assessments supported capacity building efforts for improved global influenza surveillance. METHODS: In 2010, 35 national influenza laboratories were assessed in 34 countries, using a standardized tool. Post-assessment, each laboratory received a report with a list of recommendations for improvement. Uptake of recommendations were reviewed 3.2 mean years after the initial assessments and categorized as complete, in-progress, no action or no update. This was a retrospective study; follow-up took place through routine project management rather than at a set time-point post-assessment. WHO data on National Influenza Centre (NIC) designation, External Quality Assessment Project (EQAP) participation and FluNet reporting was used to measure laboratory capacity longitudinally and independently of the assessments. All data was further stratified by World Bank country income category. RESULTS: At follow-up, 81 % of 614 recommendations were either complete (350) or in-progress (145) for 32 laboratories (91 % response rate). The number of countries reporting to FluNet and the number of specimens they reported annually increased between 2005, when they were first funded by CDC, and 2010, the assessment year (p < 0.01). Improvements were also seen in EQAP participation and NIC designation over time and more so for low and lower-middle income countries. CONCLUSIONS: Assessments using a standardized tool have been beneficial to improving laboratory-based influenza surveillance. Specific recommendations helped countries identify and prioritize areas for improvement. Data from assessments helped CDC focus its technical assistance by country and region. Low and lower-middle income countries made greater improvements in their laboratories compared with upper-middle income countries. Future research could include an analysis of annual funding and technical assistance by country. Our approach serves as an example for capacity building for other diseases.",2015 Nov 6,"['Johnson, Lucinda E. A.', 'Muir-Paulik, Sarah A.', 'Kennedy, Pam', 'Lindstrom, Steven', 'Balish, Amanda', 'Aden, Tricia', 'Moen, Ann C.']",BMC Infect Dis,,,True
3d91360fc7a5df1058b9db9e8615ffef804edacf,PMC,Use of ward closure to control outbreaks among hospitalized patients in acute care settings: a systematic review,http://dx.doi.org/10.1186/s13643-015-0131-2,PMC4636845,26546048,CC BY,"BACKGROUND: Though often used to control outbreaks, the efficacy of ward closure is unclear. This systematic review sought to identify studies defining and describing ward closure in outbreak control and to determine impact of ward closure as an intervention on outbreak containment. METHODS: We searched these databases with no language restrictions: MEDLINE, 1946 to 7 July 2014; EMBASE, 1974 to 7 July 2014; CINAHL, 1937 to 8 July 2014; and Cochrane Database of Systematic Reviews, 2005 to May 2014. We also searched the following: IndMED; LILACS; reference lists from retrieved articles; conference proceedings; and websites of the CDCP, the ICID, and the WHO. We included studies of patients hospitalized in acute care facilities; used ward closure as a control measure; used other control measures; and discussed control of the outbreak(s) under investigation. A component approach was used to assess study quality. RESULTS: We included 97 English and non-English observational studies. None included a controlled comparison between ward closure and other interventions. We found that ward closure was often used as part of a bundle of interventions but could not determine its direct impact separate from all the other interventions whether used in parallel or in sequence with other interventions. We also found no universal definition of ward closure which was widely accepted. CONCLUSIONS: With no published controlled studies identified, ward closure for control of outbreaks remains an intervention that is not evidence based and healthcare personnel will need to continue to balance the competing risks associated with its use, taking into consideration the nature of the outbreak, the type of pathogen and its virulence, mode of transmission, and the setting in which it occurs. Our review has identified a major research gap in this area. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13643-015-0131-2) contains supplementary material, which is available to authorized users.",2015 Nov 7,"['Wong, Holly', 'Eso, Katherine', 'Ip, Ada', 'Jones, Jessica', 'Kwon, Yoojin', 'Powelson, Susan', 'de Grood, Jill', 'Geransar, Rose', 'Santana, Maria', 'Joffe, A. Mark', 'Taylor, Geoffrey', 'Missaghi, Bayan', 'Pearce, Craig', 'Ghali, William A.', 'Conly, John']",Syst Rev,,,True
8806dfedc1367125f90ab8479b99ae5a50438c1a,PMC,Viral Interference and Persistence in Mosquito-Borne Flaviviruses,http://dx.doi.org/10.1155/2015/873404,PMC4637105,26583158,CC BY,"Mosquito-borne flaviviruses are important pathogens for humans, and the detection of two or more flaviviruses cocirculating in the same geographic area has often been reported. However, the epidemiological impact remains to be determined. Mosquito-borne flaviviruses are primarily transmitted through Aedes and Culex mosquitoes; these viruses establish a life-long or persistent infection without apparent pathological effects. This establishment requires a balance between virus replication and the antiviral host response. Viral interference is a phenomenon whereby one virus inhibits the replication of other viruses, and this condition is frequently associated with persistent infections. Viral interference and persistent infection are determined by several factors, such as defective interfering particles, competition for cellular factors required for translation/replication, and the host antiviral response. The interaction between two flaviviruses typically results in viral interference, indicating that these viruses share common features during the replicative cycle in the vector. The potential mechanisms involved in these processes are reviewed here.",2015 Oct 25,"['Salas-Benito, Juan Santiago', 'De Nova-Ocampo, Mónica']",J Immunol Res,,,True
eb1b9685e0eaa51bef8c8a20729643d888e0a324,PMC,Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines,http://dx.doi.org/10.1155/2015/785634,PMC4637118,26583156,CC BY,"In therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. Since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypes in situ. This review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted and finally question the true meaning of targeting antitumor-based vaccines.",2015 Oct 25,"['Goyvaerts, Cleo', 'Breckpot, Karine']",J Immunol Res,,,True
4e2c3b2b1b0da1299137c4193203f4aee8862eb3,PMC,Targeting vascular leakage in lung inflammation,,PMC4637277,26305720,CC BY,,2015 Jul 20,"['Li, Liang', 'Chow, Vincent T.K.', 'Tan, Nguan Soon']",Oncotarget,,,False
dfbdc96a5b50298935fd2f810339bdd055cb25fb,PMC,Regional health governance: A suggested agenda for Southern African health diplomacy,http://dx.doi.org/10.1177/1468018115599817,PMC4639828,26635498,CC BY,"Regional organisations can effectively promote regional health diplomacy and governance through engagement with regional social policy. Regional bodies make decisions about health challenges in the region, for example, the Union of South American Nations (UNASUR) and the World Health Organisation South East Asia Regional Office (WHO-SEARO). The Southern African Development Community (SADC) has a limited health presence as a regional organisation and diplomatic partner in health governance. This article identifies how SADC facilitates and coordinates health policy, arguing that SADC has the potential to promote regional health diplomacy and governance through engagement with regional social policy. The article identifies the role of global health diplomacy and niche diplomacy in health governance. The role of SADC as a regional organisation and the way it functions is then explained, focusing on how SADC engages with health issues in the region. Recommendations are made as to how SADC can play a more decisive role as a regional organisation to implement South–South management of the regional social policy, health governance and health diplomacy agenda.",2015 Dec,"['Penfold, Erica Dale', 'Fourie, Pieter']",Glob Soc Policy,,,True
32c89e23750b5dbc17e97eecfc5e916c15600ebe,PMC,"What’s in a word? The framing of health at the regional level: ASEAN, EU, SADC and UNASUR",http://dx.doi.org/10.1177/1468018115599816,PMC4639831,26635496,CC BY,"The Association of Southeast Asian Nations, the European Union, the Southern African Development Community and the Union of South American Nations have increasingly been involved in health diplomacy in the past decade, yet little is known about how they frame health as a foreign policy issue and how this has an impact on their prioritisation of policies. For this, we conducted a review of existing grey and peer-reviewed literature that address regional integration and health, as well as a documentary review according to security, development, trade, human rights, moral/ethical reasonings and global public goods frames identified in the literature. The policy frames identified responded to the challenges these regions currently face. The Association of Southeast Asian Nation’s struggle with re-emerging diseases has led to favouring a securitisation approach to health, the European Union approaches health as a cross-cutting policy issue, the Southern African Development Community presents health as a driver for development, and while the Union of South American Nations emphasises health as a human right and addresses the social determinants of health as an ethical imperative. Overall, these policy frames were useful in analysing the framing of health in foreign policy at the regional level. However, within our analysis, we identified a new frame that approaches health as an intersectoral issue. The impact of regional organisations’ forward will depend on their ability to harness their convening power and speak in a coherent voice on health matters.",2015 Dec,"['Amaya, Ana B', 'Rollet, Vincent', 'Kingah, Stephen']",Glob Soc Policy,,,True
c657f35b61e4e8e4ba9c06f72da78131608a4a85,PMC,Stretching health diplomacy beyond ‘Global’ problem solving: Bringing the regional normative dimension in,http://dx.doi.org/10.1177/1468018115599820,PMC4639834,26635500,CC BY,"The importance of the regional dimension of health diplomacy is only gaining slow and uneven recognition. This is in many ways surprising. As demonstrated in the work of Deacon on the ‘globalization of social policy’, global social policy has been animated and debated not only at the multilateral level but at the regional level as well. But at least in the diplomatic literature, the importance of this regional dynamic (with a focus on diverse sites and actors and the pursuit of democratic control) has been missed. The objective of this article is to explore whether health diplomacy is catching up to this larger debate re-shaping the conceptualization and practice of diplomacy more generally. In some ways, the results may be counter-productive in that this shift may encourage an increasingly fragmented process. Yet, it may also point to some breakthroughs, with diplomats, acting as ‘go to’ personnel on the front lines of operational activity, enabling actors to integrate with one another to produce effective governance. In doing so, the regional dimension is given greater recognition as a component of health diplomacy, albeit in an uneven and sometimes awkward manner. Whereas global diplomacy generally emphasizes problem solving, the regional dimension is animated by a normative orientation.",2015 Dec,"['Cooper, Andrew F', 'Farooq, Asif B']",Glob Soc Policy,,,True
4b0552782eeeefd0e22a8f2c7ff55351ec6f0c3a,PMC,A Simulation Study Comparing Epidemic Dynamics on Exponential Random Graph and Edge-Triangle Configuration Type Contact Network Models,http://dx.doi.org/10.1371/journal.pone.0142181,PMC4640514,26555701,CC BY,"We compare two broad types of empirically grounded random network models in terms of their abilities to capture both network features and simulated Susceptible-Infected-Recovered (SIR) epidemic dynamics. The types of network models are exponential random graph models (ERGMs) and extensions of the configuration model. We use three kinds of empirical contact networks, chosen to provide both variety and realistic patterns of human contact: a highly clustered network, a bipartite network and a snowball sampled network of a “hidden population”. In the case of the snowball sampled network we present a novel method for fitting an edge-triangle model. In our results, ERGMs consistently capture clustering as well or better than configuration-type models, but the latter models better capture the node degree distribution. Despite the additional computational requirements to fit ERGMs to empirical networks, the use of ERGMs provides only a slight improvement in the ability of the models to recreate epidemic features of the empirical network in simulated SIR epidemics. Generally, SIR epidemic results from using configuration-type models fall between those from a random network model (i.e., an Erdős-Rényi model) and an ERGM. The addition of subgraphs of size four to edge-triangle type models does improve agreement with the empirical network for smaller densities in clustered networks. Additional subgraphs do not make a noticeable difference in our example, although we would expect the ability to model cliques to be helpful for contact networks exhibiting household structure.",2015 Nov 10,"['Rolls, David A.', 'Wang, Peng', 'McBryde, Emma', 'Pattison, Philippa', 'Robins, Garry']",PLoS One,,,True
83649d575751ec9e3d8f1a8159da8c7f269fdc9f,PMC,A Simulation Study Comparing Epidemic Dynamics on Exponential Random Graph and Edge-Triangle Configuration Type Contact Network Models,http://dx.doi.org/10.1371/journal.pone.0142181,PMC4640514,26555701,CC BY,"We compare two broad types of empirically grounded random network models in terms of their abilities to capture both network features and simulated Susceptible-Infected-Recovered (SIR) epidemic dynamics. The types of network models are exponential random graph models (ERGMs) and extensions of the configuration model. We use three kinds of empirical contact networks, chosen to provide both variety and realistic patterns of human contact: a highly clustered network, a bipartite network and a snowball sampled network of a “hidden population”. In the case of the snowball sampled network we present a novel method for fitting an edge-triangle model. In our results, ERGMs consistently capture clustering as well or better than configuration-type models, but the latter models better capture the node degree distribution. Despite the additional computational requirements to fit ERGMs to empirical networks, the use of ERGMs provides only a slight improvement in the ability of the models to recreate epidemic features of the empirical network in simulated SIR epidemics. Generally, SIR epidemic results from using configuration-type models fall between those from a random network model (i.e., an Erdős-Rényi model) and an ERGM. The addition of subgraphs of size four to edge-triangle type models does improve agreement with the empirical network for smaller densities in clustered networks. Additional subgraphs do not make a noticeable difference in our example, although we would expect the ability to model cliques to be helpful for contact networks exhibiting household structure.",2015 Nov 10,"['Rolls, David A.', 'Wang, Peng', 'McBryde, Emma', 'Pattison, Philippa', 'Robins, Garry']",PLoS One,,,False
00af80743cef9bd8c04c532d74e9c67f0c9312e4,PMC,A Simulation Study Comparing Epidemic Dynamics on Exponential Random Graph and Edge-Triangle Configuration Type Contact Network Models,http://dx.doi.org/10.1371/journal.pone.0142181,PMC4640514,26555701,CC BY,"We compare two broad types of empirically grounded random network models in terms of their abilities to capture both network features and simulated Susceptible-Infected-Recovered (SIR) epidemic dynamics. The types of network models are exponential random graph models (ERGMs) and extensions of the configuration model. We use three kinds of empirical contact networks, chosen to provide both variety and realistic patterns of human contact: a highly clustered network, a bipartite network and a snowball sampled network of a “hidden population”. In the case of the snowball sampled network we present a novel method for fitting an edge-triangle model. In our results, ERGMs consistently capture clustering as well or better than configuration-type models, but the latter models better capture the node degree distribution. Despite the additional computational requirements to fit ERGMs to empirical networks, the use of ERGMs provides only a slight improvement in the ability of the models to recreate epidemic features of the empirical network in simulated SIR epidemics. Generally, SIR epidemic results from using configuration-type models fall between those from a random network model (i.e., an Erdős-Rényi model) and an ERGM. The addition of subgraphs of size four to edge-triangle type models does improve agreement with the empirical network for smaller densities in clustered networks. Additional subgraphs do not make a noticeable difference in our example, although we would expect the ability to model cliques to be helpful for contact networks exhibiting household structure.",2015 Nov 10,"['Rolls, David A.', 'Wang, Peng', 'McBryde, Emma', 'Pattison, Philippa', 'Robins, Garry']",PLoS One,,,True
cf27e2301131c5cb6d5b67e2dd29eff6f31ead18,PMC,A Simulation Study Comparing Epidemic Dynamics on Exponential Random Graph and Edge-Triangle Configuration Type Contact Network Models,http://dx.doi.org/10.1371/journal.pone.0142181,PMC4640514,26555701,CC BY,"We compare two broad types of empirically grounded random network models in terms of their abilities to capture both network features and simulated Susceptible-Infected-Recovered (SIR) epidemic dynamics. The types of network models are exponential random graph models (ERGMs) and extensions of the configuration model. We use three kinds of empirical contact networks, chosen to provide both variety and realistic patterns of human contact: a highly clustered network, a bipartite network and a snowball sampled network of a “hidden population”. In the case of the snowball sampled network we present a novel method for fitting an edge-triangle model. In our results, ERGMs consistently capture clustering as well or better than configuration-type models, but the latter models better capture the node degree distribution. Despite the additional computational requirements to fit ERGMs to empirical networks, the use of ERGMs provides only a slight improvement in the ability of the models to recreate epidemic features of the empirical network in simulated SIR epidemics. Generally, SIR epidemic results from using configuration-type models fall between those from a random network model (i.e., an Erdős-Rényi model) and an ERGM. The addition of subgraphs of size four to edge-triangle type models does improve agreement with the empirical network for smaller densities in clustered networks. Additional subgraphs do not make a noticeable difference in our example, although we would expect the ability to model cliques to be helpful for contact networks exhibiting household structure.",2015 Nov 10,"['Rolls, David A.', 'Wang, Peng', 'McBryde, Emma', 'Pattison, Philippa', 'Robins, Garry']",PLoS One,,,True
d7433f2be08b0e833cb270ee2ac736dce1e1a98e,PMC,A Simulation Study Comparing Epidemic Dynamics on Exponential Random Graph and Edge-Triangle Configuration Type Contact Network Models,http://dx.doi.org/10.1371/journal.pone.0142181,PMC4640514,26555701,CC BY,"We compare two broad types of empirically grounded random network models in terms of their abilities to capture both network features and simulated Susceptible-Infected-Recovered (SIR) epidemic dynamics. The types of network models are exponential random graph models (ERGMs) and extensions of the configuration model. We use three kinds of empirical contact networks, chosen to provide both variety and realistic patterns of human contact: a highly clustered network, a bipartite network and a snowball sampled network of a “hidden population”. In the case of the snowball sampled network we present a novel method for fitting an edge-triangle model. In our results, ERGMs consistently capture clustering as well or better than configuration-type models, but the latter models better capture the node degree distribution. Despite the additional computational requirements to fit ERGMs to empirical networks, the use of ERGMs provides only a slight improvement in the ability of the models to recreate epidemic features of the empirical network in simulated SIR epidemics. Generally, SIR epidemic results from using configuration-type models fall between those from a random network model (i.e., an Erdős-Rényi model) and an ERGM. The addition of subgraphs of size four to edge-triangle type models does improve agreement with the empirical network for smaller densities in clustered networks. Additional subgraphs do not make a noticeable difference in our example, although we would expect the ability to model cliques to be helpful for contact networks exhibiting household structure.",2015 Nov 10,"['Rolls, David A.', 'Wang, Peng', 'McBryde, Emma', 'Pattison, Philippa', 'Robins, Garry']",PLoS One,,,True
207f7aeed7a6907c94d4b00ed07e2ce3ded10ded,PMC,High Incidence of Mammalian Orthoreovirus Identified by Environmental Surveillance in Taiwan,http://dx.doi.org/10.1371/journal.pone.0142745,PMC4640864,26555962,CC BY,"Wild poliovirus (WPV) persists in diverse locales worldwide, spreading outward from endemic areas. In response to the international threat of WPV transmission and changes in the national vaccination policy, we established an environmental surveillance system to monitor the circulation of wild and vaccine-related poliovirus in Taiwan. From July 2012 to December 2013, we collected sewage specimens every month from 10 sewage treatment plants located throughout Taiwan. The specimens were concentrated by the two-phase separation method and then inoculated into L20B, RD, and A549 cells for virus isolation. Viral isolates were identified and serotyped by immunofluorescence assay or molecular analysis. A total of 300 sewage samples were collected, and the results showed 163 samples (54.3%) were positive for virus, and 268 isolates were identified. Among these, 75 samples (25%) were positive for enterovirus (EV), but no poliovirus was found. In addition, 92 isolates were identified as enteroviruses and the most common serotypes were coxsackievirus B4, coxsackievirus B3, and coxsackievirus B2. Interestingly, 102 (34%) and 82 (27.3%) specimens were positive for mammalian orthoreovirus (MRV) and adenovirus, respectively. This study confirmed that sewage surveillance can be a useful additional modality for monitoring the possible presence of wild-type or vaccine-derived poliovirus in wastewater, and can indicate the current types of viruses circulating in the population. Furthermore, since MRV was found in children with acute necrotizing encephalopathy and meningitis, the high incidence of MRV detected by environmental surveillance warrants further investigation.",2015 Nov 10,"['Lim, Matthew C. Y.', 'Wang, Ya-Fang', 'Huang, Sheng-Wen', 'Yang, Jyh-Yuan', 'Wang, Jen-Ren']",PLoS One,,,True
36e757c81ded2a278e917ab9030d1f682e4c4b9f,PMC,Pattern of patients and diseases during mass transit: The day of Arafat experience,http://dx.doi.org/10.12669/pjms.315.8017,PMC4641263,26648994,CC BY,"BACKGROUND AND OBJECTIVE: Every year 2-3 million Muslims gather for a few days around the Holy city of Makkah in Saudi Arabia to perform Hajj. Managing enormous health issues associated with such a mass gathering requires a very vibrant health delivery plan. Related research is part of the strategy. This study was done to assess the pattern of patients and illnesses encountered at one health facility at Arafat on the 2nd day of Hajj, when all the pilgrims move from Mina and stay in Arafat for a few hours. The objective of the study was to provide input so that recommendations can be given for future improvement of health care during this mass transit. METHODS: All patients reporting sick to the Nimra Hospital on the Day of Arafat were included and documented on a detailed Performa and analyzed. RESULTS: We received 211 patients, essentially all of those were in need of acute medical intervention. Acute severe asthma and injuries were the major problems encountered. There were two deaths both related to heat stroke. Patients received were predominantly Arabic speaking. CONCLUSIONS: Only those needing acute intervention seek medical advice during transit. Well equipped and staffed health facilities are, however, needed to cater these and for any mass casualties. Pre Hajj training and mandatory Flu vaccination can help.",2015 Sep-Oct,"['Sindy, Abdulfattah I.', 'Baljoon, Mostafa Jamil', 'Zubairi, Nadeem Alam', 'Dhafar, Khalid Obaid', 'Gazzaz, Zohair Jamil', 'Deiab, Basma Abdulhameed', 'Hothali, FauzeaTalea Al']",Pak J Med Sci,,,True
96e35195482d8911571c2242d612a317c7808caf,PMC,A census of α-helical membrane proteins in double-stranded DNA viruses infecting bacteria and archaea,http://dx.doi.org/10.1186/s12859-015-0817-4,PMC4641393,26554846,CC BY,"BACKGROUND: Viruses are the most abundant and genetically diverse biological entities on earth, yet the repertoire of viral proteins remains poorly explored. As the number of sequenced virus genomes grows into the thousands, and the number of viral proteins into the hundreds of thousands, we report a systematic computational analysis of the point of first-contact between viruses and their hosts, namely viral transmembrane (TM) proteins. RESULTS: The complement of α-helical TM proteins in double-stranded DNA viruses infecting bacteria and archaea reveals large-scale trends that differ from those of their hosts. Viruses typically encode a substantially lower fraction of TM proteins than archaea or bacteria, with the notable exception of viruses with virions containing a lipid component such as a lipid envelope, internal lipid core, or inner membrane vesicle. Compared to bacteriophages, archaeal viruses are substantially enriched in membrane proteins. However, this feature is not always stable throughout the evolution of a viral lineage; for example, TM proteins are not part of the common heritage shared between Lipothrixviridae and Rudiviridae. In contrast to bacteria and archaea, viruses almost completely lack proteins with complicated membrane topologies composed of more than 4 TM segments, with the few detected exceptions being obvious cases of relatively recent horizontal transfer from the host. CONCLUSIONS: The dramatic differences between the membrane proteomes of cells and viruses stem from the fact that viruses do not depend on essential membranes for energy transformation, ion homeostasis, nutrient transport and signaling. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0817-4) contains supplementary material, which is available to authorized users.",2015 Nov 10,"['Kristensen, David M.', 'Saeed, Usman', 'Frishman, Dmitrij', 'Koonin, Eugene V.']",BMC Bioinformatics,,,True
d0ad5a9116068caa5f78a95f8141a2a811662793,PMC,Modular approach to customise sample preparation procedures for viral metagenomics: a reproducible protocol for virome analysis,http://dx.doi.org/10.1038/srep16532,PMC4642273,26559140,CC BY,"A major limitation for better understanding the role of the human gut virome in health and disease is the lack of validated methods that allow high throughput virome analysis. To overcome this, we evaluated the quantitative effect of homogenisation, centrifugation, filtration, chloroform treatment and random amplification on a mock-virome (containing nine highly diverse viruses) and a bacterial mock-community (containing four faecal bacterial species) using quantitative PCR and next-generation sequencing. This resulted in an optimised protocol that was able to recover all viruses present in the mock-virome and strongly alters the ratio of viral versus bacterial and 16S rRNA genetic material in favour of viruses (from 43.2% to 96.7% viral reads and from 47.6% to 0.19% bacterial reads). Furthermore, our study indicated that most of the currently used virome protocols, using small filter pores and/or stringent centrifugation conditions may have largely overlooked large viruses present in viromes. We propose NetoVIR (Novel enrichment technique of VIRomes), which allows for a fast, reproducible and high throughput sample preparation for viral metagenomics studies, introducing minimal bias. This procedure is optimised mainly for faecal samples, but with appropriate concentration steps can also be used for other sample types with lower initial viral loads.",2015 Nov 12,"['Conceição-Neto, Nádia', 'Zeller, Mark', 'Lefrère, Hanne', 'De Bruyn, Pieter', 'Beller, Leen', 'Deboutte, Ward', 'Yinda, Claude Kwe', 'Lavigne, Rob', 'Maes, Piet', 'Ranst, Marc Van', 'Heylen, Elisabeth', 'Matthijnssens, Jelle']",Sci Rep,,,True
6f14312d95463d446d7f58d981a725f9efe2b5b4,PMC,Modular approach to customise sample preparation procedures for viral metagenomics: a reproducible protocol for virome analysis,http://dx.doi.org/10.1038/srep16532,PMC4642273,26559140,CC BY,"A major limitation for better understanding the role of the human gut virome in health and disease is the lack of validated methods that allow high throughput virome analysis. To overcome this, we evaluated the quantitative effect of homogenisation, centrifugation, filtration, chloroform treatment and random amplification on a mock-virome (containing nine highly diverse viruses) and a bacterial mock-community (containing four faecal bacterial species) using quantitative PCR and next-generation sequencing. This resulted in an optimised protocol that was able to recover all viruses present in the mock-virome and strongly alters the ratio of viral versus bacterial and 16S rRNA genetic material in favour of viruses (from 43.2% to 96.7% viral reads and from 47.6% to 0.19% bacterial reads). Furthermore, our study indicated that most of the currently used virome protocols, using small filter pores and/or stringent centrifugation conditions may have largely overlooked large viruses present in viromes. We propose NetoVIR (Novel enrichment technique of VIRomes), which allows for a fast, reproducible and high throughput sample preparation for viral metagenomics studies, introducing minimal bias. This procedure is optimised mainly for faecal samples, but with appropriate concentration steps can also be used for other sample types with lower initial viral loads.",2015 Nov 12,"['Conceição-Neto, Nádia', 'Zeller, Mark', 'Lefrère, Hanne', 'De Bruyn, Pieter', 'Beller, Leen', 'Deboutte, Ward', 'Yinda, Claude Kwe', 'Lavigne, Rob', 'Maes, Piet', 'Ranst, Marc Van', 'Heylen, Elisabeth', 'Matthijnssens, Jelle']",Sci Rep,,,False
055bc4fbdbbe262da7684e89ea4cfcc154a42291,PMC,Self-reactive CD4(+) T cells activated during viral-induced demyelination do not prevent clinical recovery,http://dx.doi.org/10.1186/s12974-015-0426-1,PMC4642610,26559484,CC BY,"BACKGROUND: Microbial infections have been implicated in initiating and enhancing severity of autoimmune diseases including the demyelinating disease multiple sclerosis (MS). Nevertheless, the incidence of both acute and persisting viral infections without evidence of autoimmune sequelae suggests that this process is well controlled. The conditions promoting or stemming self-reactive (SR) T cells following viral-induced tissue damage thus need to be better defined. Using a non-fatal viral mouse model of encephalomyelitis associated with demyelination and disability, yet ultimate clinical improvement, this study set out to monitor uptake and presentation of endogenous myelin antigens, as well as induction and fate of SR T cells. METHODS: Activation and central nervous system (CNS) recruitment of myelin-specific CD4 T cells was analyzed by flow cytometry during encephalomyelitis induced by a glia tropic murine coronavirus. Potential antigen-presenting cells (APC) ingesting myelin were characterized by flow cytometry and their ability to activate SR T cells tested by co-culture with carboxyfluorescein succinimidyl ester (CFSE)-labeled myelin-specific CD4 T cells. Endogenous SR T cell kinetics was analyzed within both cervical lymph nodes and CNS by Enzyme-Linked ImmunoSpot (ELISPOT) following viral infection. RESULTS: The data demonstrate the presence of APC capable of activating SR T cells in both draining lymph nodes and the CNS temporally correlating with overt demyelination. While both the CNS-infiltrating myeloid population and microglia ingested myelin, only CNS-infiltrating APC were capable of presenting endogenous myelin antigen to SR T cells ex vivo. Finally, SR T cell activation from the endogenous T cell repertoire was most notable when infectious virus was controlled and paralleled myelin damage. Although SR T cell accumulation peaked in the persistently infected CNS during maximal demyelination, they were not preferentially retained. Their gradual decline, despite ongoing demyelination, suggested minimal re-stimulation and pathogenic function in vivo consistent with the lack of autoimmune symptoms. CONCLUSIONS: The results demonstrate the potential for CNS tissue destruction to induce and recruit SR T cells to the injury site and support a host suppressive mechanism limiting development of autoimmunity.",2015 Nov 11,"['Savarin, Carine', 'Bergmann, Cornelia C.', 'Gaignage, Melanie', 'Stohlman, Stephen A.']",J Neuroinflammation,,,True
015a5be4701f244a51d6c244c2ba5b69ac68dd9d,PMC,Interferon-γ Inhibits Ebola Virus Infection,http://dx.doi.org/10.1371/journal.ppat.1005263,PMC4643030,26562011,CC BY,"Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.",2015 Nov 12,"['Rhein, Bethany A.', 'Powers, Linda S.', 'Rogers, Kai', 'Anantpadma, Manu', 'Singh, Brajesh K.', 'Sakurai, Yasuteru', 'Bair, Thomas', 'Miller-Hunt, Catherine', 'Sinn, Patrick', 'Davey, Robert A.', 'Monick, Martha M.', 'Maury, Wendy']",PLoS Pathog,,,True
ec9faa32c45199e8fec10c7a0d3bae3dd0275744,PMC,"Phylogenetic Exploration of Nosocomial Transmission Chains of 2009 Influenza A/H1N1 among Children Admitted at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa in 2011",http://dx.doi.org/10.1371/journal.pone.0141744,PMC4643913,26565994,CC BY,"Traditional modes of investigating influenza nosocomial transmission have entailed a combination of confirmatory molecular diagnostic testing and epidemiological investigation. Common hospital-acquired infections like influenza require a discerning ability to distinguish between viral isolates to accurately identify patient transmission chains. We assessed whether influenza hemagglutinin sequence phylogenies can be used to enrich epidemiological data when investigating the extent of nosocomial transmission over a four-month period within a paediatric Hospital in Cape Town South Africa. Possible transmission chains/channels were initially determined through basic patient admission data combined with Maximum likelihood and time-scaled Bayesian phylogenetic analyses. These analyses suggested that most instances of potential hospital-acquired infections resulted from multiple introductions of Influenza A into the hospital, which included instances where virus hemagglutinin sequences were identical between different patients. Furthermore, a general inability to establish epidemiological transmission linkage of patients/viral isolates implied that identified isolates could have originated from asymptomatic hospital patients, visitors or hospital staff. In contrast, a traditional epidemiological investigation that used no viral phylogenetic analyses, based on patient co-admission into specific wards during a particular time-frame, suggested that multiple hospital acquired infection instances may have stemmed from a limited number of identifiable index viral isolates/patients. This traditional epidemiological analysis by itself could incorrectly suggest linkage between unrelated cases, underestimate the number of unique infections and may overlook the possible diffuse nature of hospital transmission, which was suggested by sequencing data to be caused by multiple unique introductions of influenza A isolates into individual hospital wards. We have demonstrated a functional role for viral sequence data in nosocomial transmission investigation through its ability to enrich traditional, non-molecular observational epidemiological investigation by teasing out possible transmission pathways and working toward more accurately enumerating the number of possible transmission events.",2015 Nov 13,"['Valley-Omar, Ziyaad', 'Nindo, Fredrick', 'Mudau, Maanda', 'Hsiao, Marvin', 'Martin, Darren Patrick']",PLoS One,,,True
082c4a3189859a27a7828ebdaffad450896216bc,PMC,"Phylogenetic Exploration of Nosocomial Transmission Chains of 2009 Influenza A/H1N1 among Children Admitted at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa in 2011",http://dx.doi.org/10.1371/journal.pone.0141744,PMC4643913,26565994,CC BY,"Traditional modes of investigating influenza nosocomial transmission have entailed a combination of confirmatory molecular diagnostic testing and epidemiological investigation. Common hospital-acquired infections like influenza require a discerning ability to distinguish between viral isolates to accurately identify patient transmission chains. We assessed whether influenza hemagglutinin sequence phylogenies can be used to enrich epidemiological data when investigating the extent of nosocomial transmission over a four-month period within a paediatric Hospital in Cape Town South Africa. Possible transmission chains/channels were initially determined through basic patient admission data combined with Maximum likelihood and time-scaled Bayesian phylogenetic analyses. These analyses suggested that most instances of potential hospital-acquired infections resulted from multiple introductions of Influenza A into the hospital, which included instances where virus hemagglutinin sequences were identical between different patients. Furthermore, a general inability to establish epidemiological transmission linkage of patients/viral isolates implied that identified isolates could have originated from asymptomatic hospital patients, visitors or hospital staff. In contrast, a traditional epidemiological investigation that used no viral phylogenetic analyses, based on patient co-admission into specific wards during a particular time-frame, suggested that multiple hospital acquired infection instances may have stemmed from a limited number of identifiable index viral isolates/patients. This traditional epidemiological analysis by itself could incorrectly suggest linkage between unrelated cases, underestimate the number of unique infections and may overlook the possible diffuse nature of hospital transmission, which was suggested by sequencing data to be caused by multiple unique introductions of influenza A isolates into individual hospital wards. We have demonstrated a functional role for viral sequence data in nosocomial transmission investigation through its ability to enrich traditional, non-molecular observational epidemiological investigation by teasing out possible transmission pathways and working toward more accurately enumerating the number of possible transmission events.",2015 Nov 13,"['Valley-Omar, Ziyaad', 'Nindo, Fredrick', 'Mudau, Maanda', 'Hsiao, Marvin', 'Martin, Darren Patrick']",PLoS One,,,False
5bd0d5db60f72689e429b6f1e98678d789930366,PMC,Early-Life Exposure to Clostridium leptum Causes Pulmonary Immunosuppression,http://dx.doi.org/10.1371/journal.pone.0141717,PMC4643994,26565810,CC BY,"INTRODUCTION: Low Clostridium leptum levels are a risk factor for the development of asthma. C. leptum deficiency exacerbates asthma; however, the impact of early-life C. leptum exposure on cesarean-delivered mice remains unclear. This study is to determine the effects of early-life C. leptum exposure on asthma development in infant mice. METHODS: We exposed infant mice to C. leptum (fed-CL) and then induced asthma using the allergen ovalbumin (OVA). RESULTS: Fed-CL increased regulatory T (Treg) cells in cesarean-delivered mice compared with vaginally delivered mice. Compared with OVA-exposed mice, mice exposed to C. leptum + OVA did not develop the typical asthma phenotype, which includes airway hyper-responsiveness, cell infiltration, and T helper cell subset (Th1, Th2, Th9, Th17) inflammation. Early-life C. leptum exposure induced an immunosuppressive environment in the lung concurrent with increased Treg cells, resulting in the inhibition of Th1, Th2, Th9, and Th17 cell responses. CONCLUSION: These findings demonstrate a mechanism whereby C. leptum exposure modulates adaptive immunity and leads to failure to develop asthma upon OVA sensitization later in life.",2015 Nov 13,"['Huang, Fei', 'Qiao, Hong-mei', 'Yin, Jia-ning', 'Gao, Yang', 'Ju, Yang-hua', 'Li, Ya-nan']",PLoS One,,,True
e8ae9d6178f8322e2f9b2453ef13bb312427bd15,PMC,Identify-Isolate-Inform: A Modified Tool for Initial Detection and Management of Middle East Respiratory Syndrome Patients in the Emergency Department,http://dx.doi.org/10.5811/westjem.2015.7.27915,PMC4644025,26587081,CC BY,"Middle East respiratory syndrome (MERS) is a novel infectious disease caused by a coronavirus (MERS-CoV) first reported in Saudi Arabia in September 2012. MERS later spread to other countries in the Arabian Peninsula, followed by an outbreak in South Korea in 2015. At least 26 countries have reported MERS cases, and these numbers may increase over time. Due to international travel opportunities, all countries are at risk of imported cases of MERS, even if outbreaks do not spread globally. Therefore, it is essential for emergency department (ED) personnel to be able to rapidly assess MERS risk and take immediate actions if indicated. The Identify-Isolate-Inform (3I) tool, originally conceived for initial detection and management of Ebola virus disease patients in the ED and later adjusted for measles, can be adapted for real-time use for any emerging infectious disease. This paper reports a modification of the 3I tool for use in initial detection and management of patients under investigation for MERS. Following an assessment of epidemiologic risk factors, including travel to countries with current MERS transmission and contact with patients with confirmed MERS within 14 days, patients are risk stratified by type of exposure coupled with symptoms of fever and respiratory illness. If criteria are met, patients must be immediately placed into airborne infection isolation (or a private room until this type of isolation is available) and the emergency practitioner must alert the hospital infection prevention and control team and the local public health department. The 3I tool will facilitate rapid categorization and triggering of appropriate time-sensitive actions for patients presenting to the ED at risk for MERS.",2015 Sep 20,"Koenig, Kristi L.",West J Emerg Med,,,True
f55b841ff2d5939a229e9a7053d26e48b5139610,PMC,Viral and bacterial etiology of severe acute respiratory illness among children < 5 years of age without influenza in Niger,http://dx.doi.org/10.1186/s12879-015-1251-y,PMC4644278,26567015,CC BY,"BACKGROUND: Globally, pneumonia is the leading cause of morbidity and mortality in children, with the highest burden experienced in sub-Saharan Africa and Asia. However, there is a dearth of information on the etiology of severe acute respiratory illness (SARI) in Africa, including Niger. METHODS: We implemented a retrospective study as part of national influenza sentinel surveillance in Niger. We randomly selected a sample of nasopharyngeal specimens collected from children <5 years of age hospitalized with SARI from January 2010 through December 2012 in Niger. The samples were selected from individuals that tested negative by real-time reverse transcription polymerase chain reaction (rRT-PCR) for influenza A and B virus. The samples were analyzed using the Fast Track Diagnostic Respiratory Pathogens 21plus Kit (BioMérieux, Luxemburg), which detects 23 respiratory pathogens including 18 viral and 5 bacterial agents. RESULTS: Among the 160 samples tested, 138 (86 %) tested positive for at least one viral or bacterial pathogen; in 22 (16 %) sample, only one pathogen was detected. We detected at least one respiratory virus in 126 (78 %) samples and at least one bacterium in 102 (64 %) samples. Respiratory syncytial virus (56/160; 35 %), rhinovirus (47/160; 29 %) and parainfluenza virus (39/160; 24 %) were the most common viral pathogens detected. Among bacterial pathogens, Streptococcus pneumoniae (90/160; 56 %) and Haemophilus influenzae type b (20/160; 12 %) predominated. CONCLUSIONS: The high prevalence of certain viral and bacterial pathogens among children <5 years of age with SARI highlights the need for continued and expanded surveillance in Niger.",2015 Nov 14,"['Lagare, Adamou', 'Maïnassara, Halima Boubacar', 'Issaka, Bassira', 'Sidiki, Ali', 'Tempia, Stefano']",BMC Infect Dis,,,True
b39a7ae61df099ef77e90893f0ae87a6b63b6586,PMC,Feline calicivirus and other respiratory pathogens in cats with Feline calicivirus-related symptoms and in clinically healthy cats in Switzerland,http://dx.doi.org/10.1186/s12917-015-0595-2,PMC4644299,26566897,CC BY,"BACKGROUND: Cats with feline calicivirus (FCV)-related symptoms are commonly presented to veterinary practitioners. Various clinical manifestations have been attributed to FCV, i.e. upper respiratory tract disease (URTD), oral ulcerations, gingivostomatitis, limping syndrome and virulent systemic disease. Additionally, healthy cats can shed FCV. The aims of this study were 1) to investigate the frequency of FCV in cats with FCV-related symptoms and in healthy cats in Switzerland, 2) to assess risk and protective factors for infection, such as signalment, housing conditions, vaccination, and co-infection with URTD-associated pathogens, and 3) to address the association between clinical symptoms and FCV infection. RESULTS: Oropharyngeal, nasal and conjunctival swabs were collected in 24 veterinary practices from 200 FCV-suspect and 100 healthy cats originating from 19 cantons of Switzerland. The samples were tested for FCV using virus isolation and reverse-transcription real-time quantitative polymerase chain reaction (qPCR) and for feline herpesvirus-1 (FHV-1), Mycoplasma felis, Chlamydophila felis, Bordetella bronchiseptica using real-time qPCR. Within the two populations (FCV-suspect/healthy), the observed PCR prevalences were: FCV 45 %/8 %, FHV-1 20 %/9 %, C. felis 8 %/1 %, B. bronchiseptica 4 %/2 %, M. felis 47 %/31 % and any co-infections thereof 40 %/14 %. Based on multivariable regression models amongst FCV-suspect cats (odds ratio [95 % confidence interval]), co-infection with M. felis (1.75 [0.97; 3.14]), group housing (2.11 [1.02; 4.34]) and intact reproductive status (1.80 [0.99; 3.28]) were found to be risk factors for FCV infection. In healthy cats, intact reproductive status (22.2 [1.85; 266.7]) and group housing (46.4 [5.70; 377.7]) were found to be associated with FCV infection. Based on an univariable approach, FCV-suspect cats were found to be significantly less often FCV-positive when vaccinated (0.48 [0.24; 0.94]). Oral ulcerations, salivation, gingivitis and stomatitis, but not classical signs of URTD were significantly associated with FCV infection (all p < 0.001). CONCLUSIONS: FCV was detected in less than half of the cats that were judged FCV-suspect by veterinary practitioners. For a clinical diagnosis, FCV-related symptoms should be revisited. FCV infection was present in some healthy cats, underlining the importance of asymptomatic carriers in FCV epidemiology. To reduce FCV-related problems in multi-cat environments, reduction of group size in addition to the generally recommended vaccination are advocated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0595-2) contains supplementary material, which is available to authorized users.",2015 Nov 13,"['Berger, Alice', 'Willi, Barbara', 'Meli, Marina L.', 'Boretti, Felicitas S.', 'Hartnack, Sonja', 'Dreyfus, Anou', 'Lutz, Hans', 'Hofmann-Lehmann, Regina']",BMC Vet Res,,,False
51efc4963ed83855fd6163713ebdbdbee66cbee9,PMC,Feline calicivirus and other respiratory pathogens in cats with Feline calicivirus-related symptoms and in clinically healthy cats in Switzerland,http://dx.doi.org/10.1186/s12917-015-0595-2,PMC4644299,26566897,CC BY,"BACKGROUND: Cats with feline calicivirus (FCV)-related symptoms are commonly presented to veterinary practitioners. Various clinical manifestations have been attributed to FCV, i.e. upper respiratory tract disease (URTD), oral ulcerations, gingivostomatitis, limping syndrome and virulent systemic disease. Additionally, healthy cats can shed FCV. The aims of this study were 1) to investigate the frequency of FCV in cats with FCV-related symptoms and in healthy cats in Switzerland, 2) to assess risk and protective factors for infection, such as signalment, housing conditions, vaccination, and co-infection with URTD-associated pathogens, and 3) to address the association between clinical symptoms and FCV infection. RESULTS: Oropharyngeal, nasal and conjunctival swabs were collected in 24 veterinary practices from 200 FCV-suspect and 100 healthy cats originating from 19 cantons of Switzerland. The samples were tested for FCV using virus isolation and reverse-transcription real-time quantitative polymerase chain reaction (qPCR) and for feline herpesvirus-1 (FHV-1), Mycoplasma felis, Chlamydophila felis, Bordetella bronchiseptica using real-time qPCR. Within the two populations (FCV-suspect/healthy), the observed PCR prevalences were: FCV 45 %/8 %, FHV-1 20 %/9 %, C. felis 8 %/1 %, B. bronchiseptica 4 %/2 %, M. felis 47 %/31 % and any co-infections thereof 40 %/14 %. Based on multivariable regression models amongst FCV-suspect cats (odds ratio [95 % confidence interval]), co-infection with M. felis (1.75 [0.97; 3.14]), group housing (2.11 [1.02; 4.34]) and intact reproductive status (1.80 [0.99; 3.28]) were found to be risk factors for FCV infection. In healthy cats, intact reproductive status (22.2 [1.85; 266.7]) and group housing (46.4 [5.70; 377.7]) were found to be associated with FCV infection. Based on an univariable approach, FCV-suspect cats were found to be significantly less often FCV-positive when vaccinated (0.48 [0.24; 0.94]). Oral ulcerations, salivation, gingivitis and stomatitis, but not classical signs of URTD were significantly associated with FCV infection (all p < 0.001). CONCLUSIONS: FCV was detected in less than half of the cats that were judged FCV-suspect by veterinary practitioners. For a clinical diagnosis, FCV-related symptoms should be revisited. FCV infection was present in some healthy cats, underlining the importance of asymptomatic carriers in FCV epidemiology. To reduce FCV-related problems in multi-cat environments, reduction of group size in addition to the generally recommended vaccination are advocated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0595-2) contains supplementary material, which is available to authorized users.",2015 Nov 13,"['Berger, Alice', 'Willi, Barbara', 'Meli, Marina L.', 'Boretti, Felicitas S.', 'Hartnack, Sonja', 'Dreyfus, Anou', 'Lutz, Hans', 'Hofmann-Lehmann, Regina']",BMC Vet Res,,,False
d7d55a2878914bb8041ddc930789df1344cb940b,PMC,Feline calicivirus and other respiratory pathogens in cats with Feline calicivirus-related symptoms and in clinically healthy cats in Switzerland,http://dx.doi.org/10.1186/s12917-015-0595-2,PMC4644299,26566897,CC BY,"BACKGROUND: Cats with feline calicivirus (FCV)-related symptoms are commonly presented to veterinary practitioners. Various clinical manifestations have been attributed to FCV, i.e. upper respiratory tract disease (URTD), oral ulcerations, gingivostomatitis, limping syndrome and virulent systemic disease. Additionally, healthy cats can shed FCV. The aims of this study were 1) to investigate the frequency of FCV in cats with FCV-related symptoms and in healthy cats in Switzerland, 2) to assess risk and protective factors for infection, such as signalment, housing conditions, vaccination, and co-infection with URTD-associated pathogens, and 3) to address the association between clinical symptoms and FCV infection. RESULTS: Oropharyngeal, nasal and conjunctival swabs were collected in 24 veterinary practices from 200 FCV-suspect and 100 healthy cats originating from 19 cantons of Switzerland. The samples were tested for FCV using virus isolation and reverse-transcription real-time quantitative polymerase chain reaction (qPCR) and for feline herpesvirus-1 (FHV-1), Mycoplasma felis, Chlamydophila felis, Bordetella bronchiseptica using real-time qPCR. Within the two populations (FCV-suspect/healthy), the observed PCR prevalences were: FCV 45 %/8 %, FHV-1 20 %/9 %, C. felis 8 %/1 %, B. bronchiseptica 4 %/2 %, M. felis 47 %/31 % and any co-infections thereof 40 %/14 %. Based on multivariable regression models amongst FCV-suspect cats (odds ratio [95 % confidence interval]), co-infection with M. felis (1.75 [0.97; 3.14]), group housing (2.11 [1.02; 4.34]) and intact reproductive status (1.80 [0.99; 3.28]) were found to be risk factors for FCV infection. In healthy cats, intact reproductive status (22.2 [1.85; 266.7]) and group housing (46.4 [5.70; 377.7]) were found to be associated with FCV infection. Based on an univariable approach, FCV-suspect cats were found to be significantly less often FCV-positive when vaccinated (0.48 [0.24; 0.94]). Oral ulcerations, salivation, gingivitis and stomatitis, but not classical signs of URTD were significantly associated with FCV infection (all p < 0.001). CONCLUSIONS: FCV was detected in less than half of the cats that were judged FCV-suspect by veterinary practitioners. For a clinical diagnosis, FCV-related symptoms should be revisited. FCV infection was present in some healthy cats, underlining the importance of asymptomatic carriers in FCV epidemiology. To reduce FCV-related problems in multi-cat environments, reduction of group size in addition to the generally recommended vaccination are advocated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0595-2) contains supplementary material, which is available to authorized users.",2015 Nov 13,"['Berger, Alice', 'Willi, Barbara', 'Meli, Marina L.', 'Boretti, Felicitas S.', 'Hartnack, Sonja', 'Dreyfus, Anou', 'Lutz, Hans', 'Hofmann-Lehmann, Regina']",BMC Vet Res,,,False
3dc77148a29d1caf25a7a345f04d61d160385734,PMC,Feline calicivirus and other respiratory pathogens in cats with Feline calicivirus-related symptoms and in clinically healthy cats in Switzerland,http://dx.doi.org/10.1186/s12917-015-0595-2,PMC4644299,26566897,CC BY,"BACKGROUND: Cats with feline calicivirus (FCV)-related symptoms are commonly presented to veterinary practitioners. Various clinical manifestations have been attributed to FCV, i.e. upper respiratory tract disease (URTD), oral ulcerations, gingivostomatitis, limping syndrome and virulent systemic disease. Additionally, healthy cats can shed FCV. The aims of this study were 1) to investigate the frequency of FCV in cats with FCV-related symptoms and in healthy cats in Switzerland, 2) to assess risk and protective factors for infection, such as signalment, housing conditions, vaccination, and co-infection with URTD-associated pathogens, and 3) to address the association between clinical symptoms and FCV infection. RESULTS: Oropharyngeal, nasal and conjunctival swabs were collected in 24 veterinary practices from 200 FCV-suspect and 100 healthy cats originating from 19 cantons of Switzerland. The samples were tested for FCV using virus isolation and reverse-transcription real-time quantitative polymerase chain reaction (qPCR) and for feline herpesvirus-1 (FHV-1), Mycoplasma felis, Chlamydophila felis, Bordetella bronchiseptica using real-time qPCR. Within the two populations (FCV-suspect/healthy), the observed PCR prevalences were: FCV 45 %/8 %, FHV-1 20 %/9 %, C. felis 8 %/1 %, B. bronchiseptica 4 %/2 %, M. felis 47 %/31 % and any co-infections thereof 40 %/14 %. Based on multivariable regression models amongst FCV-suspect cats (odds ratio [95 % confidence interval]), co-infection with M. felis (1.75 [0.97; 3.14]), group housing (2.11 [1.02; 4.34]) and intact reproductive status (1.80 [0.99; 3.28]) were found to be risk factors for FCV infection. In healthy cats, intact reproductive status (22.2 [1.85; 266.7]) and group housing (46.4 [5.70; 377.7]) were found to be associated with FCV infection. Based on an univariable approach, FCV-suspect cats were found to be significantly less often FCV-positive when vaccinated (0.48 [0.24; 0.94]). Oral ulcerations, salivation, gingivitis and stomatitis, but not classical signs of URTD were significantly associated with FCV infection (all p < 0.001). CONCLUSIONS: FCV was detected in less than half of the cats that were judged FCV-suspect by veterinary practitioners. For a clinical diagnosis, FCV-related symptoms should be revisited. FCV infection was present in some healthy cats, underlining the importance of asymptomatic carriers in FCV epidemiology. To reduce FCV-related problems in multi-cat environments, reduction of group size in addition to the generally recommended vaccination are advocated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0595-2) contains supplementary material, which is available to authorized users.",2015 Nov 13,"['Berger, Alice', 'Willi, Barbara', 'Meli, Marina L.', 'Boretti, Felicitas S.', 'Hartnack, Sonja', 'Dreyfus, Anou', 'Lutz, Hans', 'Hofmann-Lehmann, Regina']",BMC Vet Res,,,True
7697fcf19fb5548783f66563f33f7977ff59cd7a,PMC,Are Microglial Cells the Regulators of Lymphocyte Responses in the CNS?,http://dx.doi.org/10.3389/fncel.2015.00440,PMC4644801,26635525,CC BY,"The infiltration of immune cells in the central nervous system is a common hallmark in different neuroinflammatory conditions. Accumulating evidence indicates that resident glial cells can establish a cross-talk with infiltrated immune cells, including T-cells, regulating their recruitment, activation and function within the CNS. Although the healthy CNS has been thought to be devoid of professional dendritic cells (DCs), numerous studies have reported the presence of a population of DCs in specific locations such as the meninges, choroid plexuses and the perivascular space. Moreover, the infiltration of DC precursors during neuroinflammatory situations has been proposed, suggesting a putative role of these cells in the regulation of lymphocyte activity within the CNS. On the other hand, under specific circumstances, microglial cells are able to acquire a phenotype of DC expressing a wide range of molecules that equip these cells with all the necessary machinery for communication with T-cells. In this review, we summarize the current knowledge on the expression of molecules involved in the cross-talk with T-cells in both microglial cells and DCs and discuss the potential contribution of each of these cell populations on the control of lymphocyte function within the CNS.",2015 Nov 16,"['Almolda, Beatriz', 'González, Berta', 'Castellano, Bernardo']",Front Cell Neurosci,,,True
6f59c51ced3b52352e02cb226a542900b94ef5f5,PMC,Modeling [(18)F]-FDG lymphoid tissue kinetics to characterize nonhuman primate immune response to Middle East respiratory syndrome-coronavirus aerosol challenge,http://dx.doi.org/10.1186/s13550-015-0143-x,PMC4646887,26573211,CC BY,"BACKGROUND: The pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, have not been fully characterized because a suitable animal model is currently not available. (18)F-Fluorodeoxyglucose ([(18)F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [(18)F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. We used [(18)F]-FDG-PET/CT to investigate the host response developing in nonhuman primates after MERS-CoV exposure and applied kinetic modeling to monitor the influx rate constant (K(i)) in responsive lymphoid tissue. METHODS: Multiple [(18)F]-FDG-PET and CT images were acquired on a PET/CT clinical scanner modified to operate in a biosafety level 4 environment prior to and up to 29 days after MERS-CoV aerosol exposure. Time activity curves of various lymphoid tissues were reconstructed to follow the [(18)F]-FDG uptake for approximately 60 min (3,600 s). Image-derived input function was used to calculate K(i) for lymphoid tissues by Patlak plot. RESULTS: Two-way repeated measures analysis of variance revealed alterations in K(i) that was associated with the time point (p < 0.001) after virus exposure and the location of lymphoid tissue (p = 0.0004). As revealed by a statistically significant interaction (p < 0.0001) between these two factors, the pattern of K(i) changes over time differed between three locations but not between subjects. A distinguished pattern of statistically significant elevation in K(i) was observed in mediastinal lymph nodes (LNs) that correlated to K(i) changes in axillary LNs. Changes in LNs K(i) were concurrent with elevations of monocytes in peripheral blood. CONCLUSIONS: [(18)F]-FDG-PET is able to detect subtle changes in host immune response to contain a subclinical virus infection. Full quantitative analysis is the preferred approach rather than semiquantitative analysis using standardized uptake value for detection of the immune response to the virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13550-015-0143-x) contains supplementary material, which is available to authorized users.",2015 Nov 16,"['Chefer, Svetlana', 'Thomasson, David', 'Seidel, Jurgen', 'Reba, Richard C.', 'Bohannon, J. Kyle', 'Lackemeyer, Mathew G.', 'Bartos, Chris', 'Sayre, Philip J.', 'Bollinger, Laura', 'Hensley, Lisa E.', 'Jahrling, Peter B.', 'Johnson, Reed F.']",EJNMMI Res,,,False
f2f841111913d49cbbd17e0988fc4f49b06c4945,PMC,Modeling [(18)F]-FDG lymphoid tissue kinetics to characterize nonhuman primate immune response to Middle East respiratory syndrome-coronavirus aerosol challenge,http://dx.doi.org/10.1186/s13550-015-0143-x,PMC4646887,26573211,CC BY,"BACKGROUND: The pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, have not been fully characterized because a suitable animal model is currently not available. (18)F-Fluorodeoxyglucose ([(18)F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [(18)F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. We used [(18)F]-FDG-PET/CT to investigate the host response developing in nonhuman primates after MERS-CoV exposure and applied kinetic modeling to monitor the influx rate constant (K(i)) in responsive lymphoid tissue. METHODS: Multiple [(18)F]-FDG-PET and CT images were acquired on a PET/CT clinical scanner modified to operate in a biosafety level 4 environment prior to and up to 29 days after MERS-CoV aerosol exposure. Time activity curves of various lymphoid tissues were reconstructed to follow the [(18)F]-FDG uptake for approximately 60 min (3,600 s). Image-derived input function was used to calculate K(i) for lymphoid tissues by Patlak plot. RESULTS: Two-way repeated measures analysis of variance revealed alterations in K(i) that was associated with the time point (p < 0.001) after virus exposure and the location of lymphoid tissue (p = 0.0004). As revealed by a statistically significant interaction (p < 0.0001) between these two factors, the pattern of K(i) changes over time differed between three locations but not between subjects. A distinguished pattern of statistically significant elevation in K(i) was observed in mediastinal lymph nodes (LNs) that correlated to K(i) changes in axillary LNs. Changes in LNs K(i) were concurrent with elevations of monocytes in peripheral blood. CONCLUSIONS: [(18)F]-FDG-PET is able to detect subtle changes in host immune response to contain a subclinical virus infection. Full quantitative analysis is the preferred approach rather than semiquantitative analysis using standardized uptake value for detection of the immune response to the virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13550-015-0143-x) contains supplementary material, which is available to authorized users.",2015 Nov 16,"['Chefer, Svetlana', 'Thomasson, David', 'Seidel, Jurgen', 'Reba, Richard C.', 'Bohannon, J. Kyle', 'Lackemeyer, Mathew G.', 'Bartos, Chris', 'Sayre, Philip J.', 'Bollinger, Laura', 'Hensley, Lisa E.', 'Jahrling, Peter B.', 'Johnson, Reed F.']",EJNMMI Res,,,True
0e803f9a98199d4c1e322f933e9943db653460be,PMC,Development of reverse-transcription loop-mediated isothermal amplification assay for rapid detection and differentiation of dengue virus serotypes 1–4,http://dx.doi.org/10.1186/s12866-015-0595-1,PMC4647581,26572227,CC BY,"BACKGROUND: Dengue virus (DENV), the most widely prevalent arbovirus, continues to be a threat to human health in the tropics and subtropics. Early and rapid detection of DENV infection during the acute phase of illness is crucial for proper clinical patient management and preventing the spread of infection. The aim of the current study was to develop a specific, sensitive, and robust reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay for detection and differentiation of DENV1-4 serotypes. RESULTS: The method detection primers, which were designed to target the different DENV serotypes, were identified by inspection of multiple sequence alignments of the non-structural protein (NS) 2A of DENV1, NS4B of DENV2, NS4A of DENV3 and the 3′ untranslated region of the NS protein of DENV4. No cross-reactions of the four serotypes were observed during the tests. The detection limits of the DENV1-4-specific RT-LAMP assays were approximately 10-copy templates per reaction. The RT-LAMP assays were ten-fold more sensitive than RT-PCR or real-time PCR. The diagnostic rate was 100 % for clinical strains of DENV, and 98.9 % of the DENV-infected patients whose samples were tested were detected by RT-LAMP. Importantly, no false-positives were detected with the new equipment and methodology that was used to avoid aerosol contamination of the samples. CONCLUSION: The RT-LAMP method used in our study is specific, sensitive, and suitable for further investigation as a useful alternative to the current methods used for clinical diagnosis of DENV1-4, especially in hospitals and laboratories that lack sophisticated diagnostic systems.",2015 Nov 14,"['Hu, Sheng-feng', 'Li, Miao', 'Zhong, Lan-lan', 'Lu, Shi-miao', 'Liu, Ze-xia', 'Pu, Jie-ying', 'Wen, Jin-sheng', 'Huang, Xi']",BMC Microbiol,,,True
ae8c759fe82750edd66adb5e87e2ee44cb73c419,PMC,Polyethylene glycol-mediated fusion of herpes simplex type 1 virions with the plasma membrane of cells that support endocytic entry,http://dx.doi.org/10.1186/s12985-015-0423-0,PMC4647588,26573723,CC BY,"BACKGROUND: Mouse B78 cells and Chinese hamster ovary (CHO) cells are important to the study of HSV-1 entry because both are resistant to infection at the level of viral entry. When provided with a gD-receptor such as nectin-1, these cells support HSV-1 entry by an endocytosis pathway. Treating some viruses bound to cells with the fusogen polyethylene glycol (PEG) mediates viral fusion with the cell surface but is insufficient to rescue viral entry. It is unclear whether PEG-mediated fusion of HSV with the plasma membrane of B78 or CHO cells results in successful entry and infection. FINDINGS: Treating HSV-1 bound to B78 or CHO cells with PEG allowed viral entry as measured by virus-induced beta-galactosidase activity. Based on the mechanism of PEG action, we propose that entry likely proceeds by direct fusion of HSV particles with the plasma membrane. Under the conditions tested, PEG-mediated infection of CHO cells progressed to the level of HSV late gene expression, while B78 cells supported HSV DNA replication. We tested whether proteolysis or acidification of cell-bound virions could trigger HSV fusion with the plasma membrane. Under the conditions tested, mildly acidic pH of 5–6 or the protease trypsin were not capable of triggering HSV-1 fusion as compared to PEG-treated cell-bound virions. CONCLUSIONS: B78 cells and CHO cells, which typically endocytose HSV prior to viral penetration, are capable of supporting HSV-1 entry via direct penetration. HSV capsids delivered directly to the cytosol at the periphery of these cells complete the entry process. B78 and CHO cells may be utilized to screen for factors that trigger entry as a consequence of fusion of virions with the cell surface, and PEG treatment can provide a necessary control.",2015 Nov 16,"['Walker, Erik B.', 'Pritchard, Suzanne M.', 'Cunha, Cristina W.', 'Aguilar, Hector C.', 'Nicola, Anthony V.']",Virol J,,,True
f80fdfc8ac74900c266137137e0a1cd6b6e12b02,PMC,Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue,http://dx.doi.org/10.1186/s12879-015-1271-7,PMC4647599,26572220,CC BY,"BACKGROUND: Dengue is the most widespread mosquito-borne viral disease of public health concern. In some patients, endothelial cell and platelet dysfunction lead to life-threatening hemorrhagic dengue fever or dengue shock syndrome. Prognostication of disease severity is urgently required to improve patient management. The pathogenesis of severe dengue has not been fully elucidated, and the role of host proteins associated with viral particles has received little exploration. METHODS: The proteomes of virion-enriched fractions purified from plasma pools of patients with dengue fever or severe dengue were compared. Virions were purified by ultracentrifugation combined with a water-insoluble polyelectrolyte-based technique. Following in-gel hydrolysis, peptides were analyzed by nano-liquid chromatography coupled to ion trap mass spectrometry and identified using data libraries. RESULTS: Both dengue fever and severe dengue viral-enriched fractions contained identifiable viral envelope proteins and host cellular proteins. Canonical pathway analysis revealed the identified host proteins are mainly involved in the coagulation cascade, complement pathway or acute phase response signaling pathway. Some host proteins were over- or under-represented in plasma from patients with severe dengue compared to patients with dengue fever. ELISAs were used to validate differential expression of a selection of identified host proteins in individual plasma samples of patients with dengue fever compared to patients with severe dengue. Among 22 host proteins tested, two could differentiate between dengue fever and severe dengue in two independent cohorts (olfactomedin-4: area under the curve (AUC), 0.958; and platelet factor-4: AUC, 0.836). CONCLUSION: A novel technique of virion-enrichment from plasma has allowed to identify two host proteins that have prognostic value for classifying patients with acute dengue who are more likely to develop a severe dengue. The impact of these host proteins on pathogenicity and disease outcome are discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1271-7) contains supplementary material, which is available to authorized users.",2015 Nov 14,"['Fragnoud, Romain', 'Flamand, Marie', 'Reynier, Frederic', 'Buchy, Philippe', 'Duong, Vasna', 'Pachot, Alexandre', 'Paranhos-Baccala, Glaucia', 'Bedin, Frederic']",BMC Infect Dis,,,False
c0bec3dd80af76e0f60020b72ab8f6e1f14354fb,PMC,Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue,http://dx.doi.org/10.1186/s12879-015-1271-7,PMC4647599,26572220,CC BY,"BACKGROUND: Dengue is the most widespread mosquito-borne viral disease of public health concern. In some patients, endothelial cell and platelet dysfunction lead to life-threatening hemorrhagic dengue fever or dengue shock syndrome. Prognostication of disease severity is urgently required to improve patient management. The pathogenesis of severe dengue has not been fully elucidated, and the role of host proteins associated with viral particles has received little exploration. METHODS: The proteomes of virion-enriched fractions purified from plasma pools of patients with dengue fever or severe dengue were compared. Virions were purified by ultracentrifugation combined with a water-insoluble polyelectrolyte-based technique. Following in-gel hydrolysis, peptides were analyzed by nano-liquid chromatography coupled to ion trap mass spectrometry and identified using data libraries. RESULTS: Both dengue fever and severe dengue viral-enriched fractions contained identifiable viral envelope proteins and host cellular proteins. Canonical pathway analysis revealed the identified host proteins are mainly involved in the coagulation cascade, complement pathway or acute phase response signaling pathway. Some host proteins were over- or under-represented in plasma from patients with severe dengue compared to patients with dengue fever. ELISAs were used to validate differential expression of a selection of identified host proteins in individual plasma samples of patients with dengue fever compared to patients with severe dengue. Among 22 host proteins tested, two could differentiate between dengue fever and severe dengue in two independent cohorts (olfactomedin-4: area under the curve (AUC), 0.958; and platelet factor-4: AUC, 0.836). CONCLUSION: A novel technique of virion-enrichment from plasma has allowed to identify two host proteins that have prognostic value for classifying patients with acute dengue who are more likely to develop a severe dengue. The impact of these host proteins on pathogenicity and disease outcome are discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1271-7) contains supplementary material, which is available to authorized users.",2015 Nov 14,"['Fragnoud, Romain', 'Flamand, Marie', 'Reynier, Frederic', 'Buchy, Philippe', 'Duong, Vasna', 'Pachot, Alexandre', 'Paranhos-Baccala, Glaucia', 'Bedin, Frederic']",BMC Infect Dis,,,True
6dab259f3cac146d0cadf07d4085a8ecc4069bed,PMC,Tracking social contact networks with online respondent-driven detection: who recruits whom?,http://dx.doi.org/10.1186/s12879-015-1250-z,PMC4647802,26573658,CC BY,"BACKGROUND: Transmission of respiratory pathogens in a population depends on the contact network patterns of individuals. To accurately understand and explain epidemic behaviour information on contact networks is required, but only limited empirical data is available. Online respondent-driven detection can provide relevant epidemiological data on numbers of contact persons and dynamics of contacts between pairs of individuals. We aimed to analyse contact networks with respect to sociodemographic and geographical characteristics, vaccine-induced immunity and self-reported symptoms. METHODS: In 2014, volunteers from two large participatory surveillance panels in the Netherlands and Belgium were invited for a survey. Participants were asked to record numbers of contacts at different locations and self-reported influenza-like-illness symptoms, and to invite 4 individuals they had met face to face in the preceding 2 weeks. We calculated correlations between linked individuals to investigate mixing patterns. RESULTS: In total 1560 individuals completed the survey who reported in total 30591 contact persons; 488 recruiter-recruit pairs were analysed. Recruitment was assortative by age, education, household size, influenza vaccination status and sentiments, indicating that participants tended to recruit contact persons similar to themselves. We also found assortative recruitment by symptoms, reaffirming our objective of sampling contact persons whom a participant may infect or by whom a participant may get infected in case of an outbreak. Recruitment was random by sex and numbers of contact persons. Relationships between pairs were influenced by the spatial distribution of peer recruitment. CONCLUSIONS: Although complex mechanisms influence online peer recruitment, the observed statistical relationships reflected the observed contact network patterns in the general population relevant for the transmission of respiratory pathogens. This provides useful and innovative input for predictive epidemic models relying on network information. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1250-z) contains supplementary material, which is available to authorized users.",2015 Nov 14,"['Stein, Mart L.', 'van der Heijden, Peter G. M.', 'Buskens, Vincent', 'van Steenbergen, Jim E.', 'Bengtsson, Linus', 'Koppeschaar, Carl E.', 'Thorson, Anna', 'Kretzschmar, Mirjam E. E.']",BMC Infect Dis,,,True
6c04f5f55db4cef127e6799e220f5cb86b9ffa18,PMC,Tracking social contact networks with online respondent-driven detection: who recruits whom?,http://dx.doi.org/10.1186/s12879-015-1250-z,PMC4647802,26573658,CC BY,"BACKGROUND: Transmission of respiratory pathogens in a population depends on the contact network patterns of individuals. To accurately understand and explain epidemic behaviour information on contact networks is required, but only limited empirical data is available. Online respondent-driven detection can provide relevant epidemiological data on numbers of contact persons and dynamics of contacts between pairs of individuals. We aimed to analyse contact networks with respect to sociodemographic and geographical characteristics, vaccine-induced immunity and self-reported symptoms. METHODS: In 2014, volunteers from two large participatory surveillance panels in the Netherlands and Belgium were invited for a survey. Participants were asked to record numbers of contacts at different locations and self-reported influenza-like-illness symptoms, and to invite 4 individuals they had met face to face in the preceding 2 weeks. We calculated correlations between linked individuals to investigate mixing patterns. RESULTS: In total 1560 individuals completed the survey who reported in total 30591 contact persons; 488 recruiter-recruit pairs were analysed. Recruitment was assortative by age, education, household size, influenza vaccination status and sentiments, indicating that participants tended to recruit contact persons similar to themselves. We also found assortative recruitment by symptoms, reaffirming our objective of sampling contact persons whom a participant may infect or by whom a participant may get infected in case of an outbreak. Recruitment was random by sex and numbers of contact persons. Relationships between pairs were influenced by the spatial distribution of peer recruitment. CONCLUSIONS: Although complex mechanisms influence online peer recruitment, the observed statistical relationships reflected the observed contact network patterns in the general population relevant for the transmission of respiratory pathogens. This provides useful and innovative input for predictive epidemic models relying on network information. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1250-z) contains supplementary material, which is available to authorized users.",2015 Nov 14,"['Stein, Mart L.', 'van der Heijden, Peter G. M.', 'Buskens, Vincent', 'van Steenbergen, Jim E.', 'Bengtsson, Linus', 'Koppeschaar, Carl E.', 'Thorson, Anna', 'Kretzschmar, Mirjam E. E.']",BMC Infect Dis,,,True
e666325d40e18c90c35e6a6eb9b5723a28cc15ad,PMC,Respiratory consequences of N95-type Mask usage in pregnant healthcare workers—a controlled clinical study,http://dx.doi.org/10.1186/s13756-015-0086-z,PMC4647822,26579222,CC BY,"BACKGROUND: Outbreaks of emerging infectious diseases have led to guidelines recommending the routine use of N95 respirators for healthcare workers, many of whom are women of childbearing age. The respiratory effects of prolonged respirator use on pregnant women are unclear although there has been no definite evidence of harm from past use. METHODS: We conducted a two-phase controlled clinical study on healthy pregnant women between 27 to 32 weeks gestation. In phase I, energy expenditure corresponding to the workload of routine nursing tasks was determined. In phase II, pulmonary function of 20 subjects was measured whilst at rest and exercising to the predetermined workload while breathing ambient air first, then breathing through N95-mask materials. RESULTS: Exercising at 3 MET while breathing through N95-mask materials reduced mean tidal volume (TV) by 23.0 % (95 % CI −33.5 % to −10.5 %, p < 0.001) and lowered minute ventilation (VE) by 25.8 % (95 % CI −34.2 % to −15.8 %, p < 0.001), with no significant change in breathing frequency compared to breathing ambient air. Volumes of oxygen consumption (VO(2)) and carbon dioxide expired (VCO(2)) were also significantly reduced; VO(2) by 13.8 % (95 % CI −24.2 % to −3 %, p = 0.013) and VCO(2) by 17.7 %, (95 % CI −28.1 % to −8.6 %, p = 0.001). Although no changes in the inspired oxygen and carbon dioxide concentrations were demonstrated, breathing through N95-mask materials during low intensity work (3 MET) reduced expired oxygen concentration by 3.2 % (95 % CI: −4.1 % to −2.2 %, p < 0.001), and increased expired carbon dioxide by 8.9 % (95 % CI: 6.9 % to 13.1 %; p <0.001) suggesting an increase in metabolism. There were however no changes in the maternal and fetal heart rates, finger-tip capillary lactate levels and oxygen saturation and rating of perceived exertion at the work intensity investigated. CONCLUSIONS: Breathing through N95 mask materials have been shown to impede gaseous exchange and impose an additional workload on the metabolic system of pregnant healthcare workers, and this needs to be taken into consideration in guidelines for respirator use. The benefits of using N95 mask to prevent serious emerging infectious diseases should be weighed against potential respiratory consequences associated with extended N95 respirator usage. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov, identifier NCT00265926.",2015 Nov 16,"['Tong, Pearl Shuang Ye', 'Kale, Anita Sugam', 'Ng, Kailyn', 'Loke, Amelia Peiwen', 'Choolani, Mahesh Arjandas', 'Lim, Chin Leong', 'Chan, Yiong Huak', 'Chong, Yap Seng', 'Tambyah, Paul Anantharajah', 'Yong, Eu-Leong']",Antimicrob Resist Infect Control,,,True
197679559a6aa8d3f30bde60d9387f1f9f975c0a,PMC,Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia,http://dx.doi.org/10.1371/journal.pone.0143152,PMC4648489,26576054,CC BY,"OBJECTIVES: To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. DESIGN: A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. SETTING: Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. PARTICIPANTS: Ninety-one adult patients with acute respiratory infection (55% were female). MEASUREMENTS: Viral identification, intensive care unit admission, hospital stay, and mortality. RESULTS: Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. CONCLUSIONS: The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality.",2015 Nov 17,"['Remolina, Yuly Andrea', 'Ulloa, María Mercedes', 'Vargas, Hernán', 'Díaz, Liliana', 'Gómez, Sandra Liliana', 'Saavedra, Alfredo', 'Sánchez, Edgar', 'Cortés, Jorge Alberto']",PLoS One,,,True
5de6f9a65ba8f1857af0057539ff471a4427a157,PMC,Functional variants regulating LGALS1 (Galectin 1) expression affect human susceptibility to influenza A(H7N9),http://dx.doi.org/10.1038/srep08517,PMC4649671,25687228,CC BY,"The fatality of avian influenza A(H7N9) infection in humans was over 30%. To identify human genetic susceptibility to A(H7N9) infection, we performed a genome-wide association study (GWAS) involving 102 A(H7N9) patients and 106 heavily-exposed healthy poultry workers, a sample size critically restricted by the small number of human A(H7N9) cases. To tackle the stringent significance cutoff of GWAS, we utilized an artificial imputation program SnipSnip to improve the association signals. In single-SNP analysis, one of the top SNPs was rs13057866 of LGALS1. The artificial imputation (AI) identified three non-genotyped causal variants, which can be represented by three anchor/partner SNP pairs rs13057866/rs9622682 (AI P = 1.81 × 10(−7)), rs4820294/rs2899292 (2.13 × 10(−7)) and rs62236673/rs2899292 (4.25 × 10(−7)) respectively. Haplotype analysis of rs4820294 and rs2899292 could simulate the signal of a causal variant. The rs4820294/rs2899292 haplotype GG, in association with protection from A(H7N9) infection (OR = 0.26, P = 5.92 × 10(−7)) correlated to significantly higher levels of LGALS1 mRNA (P = 0.050) and protein expression (P = 0.025) in lymphoblast cell lines. Additionally, rs4820294 was mapped as an eQTL in human primary monocytes and lung tissues. In conclusion, functional variants of LGALS1 causing the expression variations are contributable to the differential susceptibility to influenza A(H7N9).",2015 Feb 17,"['Chen, Yu', 'Zhou, Jie', 'Cheng, Zhongshan', 'Yang, Shigui', 'Chu, Hin', 'Fan, Yanhui', 'Li, Cun', 'Wong, Bosco Ho-Yin', 'Zheng, Shufa', 'Zhu, Yixin', 'Yu, Fei', 'Wang, Yiyin', 'Liu, Xiaoli', 'Gao, Hainv', 'Yu, Liang', 'Tang, Linglin', 'Cui, Dawei', 'Hao, Ke', 'Bossé, Yohan', 'Obeidat, Ma′en', 'Brandsma, Corry-Anke', 'Song, You-Qiang', 'To, Kelvin Kai-Wang', 'Sham, Pak Chung', 'Yuen, Kwok-Yung', 'Li, Lanjuan']",Sci Rep,,,True
b98f753cf246353e2ffff6822aeff4f2f3c5a7b5,PMC,Antiviral Phosphorodiamidate Morpholino Oligomers are Protective against Chikungunya Virus Infection on Cell-based and Murine Models,http://dx.doi.org/10.1038/srep12727,PMC4649900,26224141,CC BY,"Chikungunya virus (CHIKV) infection in human is associated with debilitating and persistent arthralgia and arthritis. Currently, there is no specific vaccine or effective antiviral available. Anti-CHIKV Phosphorodiamidate Morpholino Oligomer (CPMO) was evaluated for its antiviral efficacy and cytotoxcity in human cells and neonate murine model. Two CPMOs were designed to block translation initiation of a highly conserved sequence in CHIKV non-structural and structural polyprotein, respectively. Pre-treatment of HeLa cells with CPMO1 signficantly suppressed CHIKV titre, CHIKV E2 protein expression and prevented CHIKV-induced CPE. CPMO1 activity was also CHIKV-specific as shown by the lack of cross-reactivity against SINV or DENV replication. When administered prophylactically in neonate mice, 15 μg/g CPMO1v conferred 100% survival against CHIKV disease. In parallel, these mice demonstrated significant reduction in viremia and viral load in various tissues. Immunohistological examination of skeletal muscles and liver of CPMO1v-treated mice also showed healthy tissue morphology, in contrast to evident manifestation of CHIKV pathogenesis in PBS- or scrambled sCPMO1v-treated groups. Taken together, our findings highlight for the first time that CPMO1v has strong protective effect against CHIKV infection. This warrants future development of morpholino as an alternative antiviral agent to address CHIKV infection in clinical applications.",2015 Jul 30,"['Lam, Shirley', 'Chen, Huixin', 'Chen, Caiyun Karen', 'Min, Nyo', 'Chu, Justin Jang Hann']",Sci Rep,,,True
7c3be5c1501f68e5305325f4acac221632ccb290,PMC,Impact of antibacterials on subsequent resistance and clinical outcomes in adult patients with viral pneumonia: an opportunity for stewardship,http://dx.doi.org/10.1186/s13054-015-1120-5,PMC4650137,26577540,CC BY,"INTRODUCTION: Respiratory viruses are increasingly recognized as significant etiologies of pneumonia among hospitalized patients. Advanced technologies using multiplex molecular assays and polymerase-chain reaction increase the ability to identify viral pathogens and may ultimately impact antibacterial use. METHOD: This was a single-center retrospective cohort study to evaluate the impact of antibacterials in viral pneumonia on clinical outcomes and subsequent multidrug-resistant organism (MDRO) infections/colonization. Patients admitted from March 2013 to November 2014 with positive respiratory viral panels (RVP) and radiographic findings of pneumonia were included. Patients transferred from an outside hospital or not still hospitalized 72 hours after the RVP report date were excluded. Patients were categorized based on exposure to systemic antibacterials: less than 3 days representing short-course therapy and 3 to 10 days being long-course therapy. RESULTS: A total of 174 patients (long-course, n = 67; short-course, n = 28; mixed bacterial-viral infection, n = 79) were included with most being immunocompromised (56.3 %) with active malignancy the primary etiology (69.4 %). Rhinovirus/Enterovirus (23 %), Influenza (19 %), and Parainfluenza (15.5 %) were the viruses most commonly identified. A total of 13 different systemic antibacterials were used as empiric therapy in the 95 patients with pure viral infection for a total of 466 days-of-therapy. Vancomycin (50.7 %), cefepime (40.3 %), azithromycin (40.3 %), meropenem (23.9 %), and linezolid (20.9 %) were most frequently used. In-hospital mortality did not differ between patients with viral pneumonia in the short-course and long-course groups. Subsequent infection/colonization with a MDRO was more frequent in the long-course group compared to the short-course group (53.2 vs 21.1 %; P = 0.027). CONCLUSION: This study found that long-course antibacterial use in the setting of viral pneumonia had no impact on clinical outcomes but increased the incidence of subsequent MDRO infection/colonization.",2015 Nov 18,"['Crotty, Matthew P.', 'Meyers, Shelby', 'Hampton, Nicholas', 'Bledsoe, Stephanie', 'Ritchie, David J.', 'Buller, Richard S.', 'Storch, Gregory A.', 'Kollef, Marin H.', 'Micek, Scott T.']",Crit Care,,,True
0f537e86e84193917fff3e7152e74148d158c5be,PMC,Actinobacillus pleuropneumoniae induces SJPL cell cycle arrest in G2/M-phase and inhibits porcine reproductive and respiratory syndrome virus replication,http://dx.doi.org/10.1186/s12985-015-0404-3,PMC4650394,26577697,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the swine industry and causes important economic losses. No effective antiviral drugs against it are commercially available. We recently reported that the culture supernatant of Actinobacillus pleuropneumoniae, the porcine pleuropneumonia causative agent, has an antiviral activity in vitro against PRRSV in SJPL cells. Objectives of this study were (i) to identify the mechanism behind the antiviral activity displayed by A. pleuropneumoniae and (ii) to characterize the active molecules present in the bacterial culture supernatant. METHODS: Antibody microarray analysis was used in order to point out cellular pathways modulated by the A. pleuropneumoniae supernatant. Subsequent, flow cytometry analysis and cell cycle inhibitors were used to confirm antibody microarray data and to link them to the antiviral activity of the A. pleuropneumoniae supernatant. Finally, A. pleuropneumoniae supernatant characterization was partially achieved using mass spectrometry. RESULTS: Using antibody microarray, we observed modulations in G2/M-phase cell cycle regulation pathway when SJPL cells were treated with A. pleuropneumoniae culture supernatant. These modulations were confirmed by a cell cycle arrest at the G2/M-phase when cells were treated with the A. pleuropneumoniae culture supernatant. Furthermore, two G2/M-phase cell cycle inhibitors demonstrated the ability to inhibit PRRSV infection, indicating a potential key role for PRRSV infection. Finally, mass spectrometry lead to identify two molecules (m/z 515.2 and m/z 663.6) present only in the culture supernatant. CONCLUSIONS: We demonstrated for the first time that A. pleuropneumoniae is able to disrupt SJPL cell cycle resulting in inhibitory activity against PRRSV. Furthermore, two putative molecules were identified from the culture supernatant. This study highlighted the cell cycle importance for PRRSV and will allow the development of new prophylactic or therapeutic approaches against PRRSV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0404-3) contains supplementary material, which is available to authorized users.",2015 Nov 14,"['Ferreira Barbosa, Jérémy A.', 'Labrie, Josée', 'Beaudry, Francis', 'Gagnon, Carl A.', 'Jacques, Mario']",Virol J,,,True
c7b980605c4ba138f35378e5f56b95e677cc87c5,PMC,Ubiquitin-specific Protease 15 Negatively Regulates Virus-induced Type I Interferon Signaling via Catalytically-dependent and -independent Mechanisms,http://dx.doi.org/10.1038/srep11220,PMC4650652,26061460,CC BY,"Viral infection triggers a series of signaling cascades, which converge to activate the transcription factors nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3), thereby inducing the transcription of type I interferons (IFNs). Although not fully characterized, these innate antiviral responses are fine-tuned by dynamic ubiquitination and deubiquitination processes. In this study, we report ubiquitin-specific protease (USP) 15 is involved in regulation of the retinoic acid-inducible gene I (RIG-I)-dependent type I IFN induction pathway. Knockdown of endogenous USP15 augmented cellular antiviral responses. Overexpression of USP15 inhibited the transcription of IFN-β. Further analyses identified histidine 862 as a critical residue for USP15’s catalytic activity. Interestingly, USP15 specifically removed lysine 63-linked polyubiquitin chains from RIG-I among the essential components in RIG-I-like receptor-dependent pathway. In addition, we demonstrated that in contrast to USP15 de-ubiquitinating (DUB) activity, USP15-mediated inhibition of IFN signaling was not abolished by mutations eliminating the catalytic activity, indicating that a fraction of USP15-mediated IFN antagonism was independent of the DUB activity. Catalytically inactive USP15 mutants, as did the wild-type protein, disrupted virus-induced interaction of RIG-I and IFN-β promoter stimulator 1. Taken together, our data demonstrate that USP15 acts as a negative regulator of RIG-I signaling via DUB-dependent and independent mechanisms.",2015 Jun 10,"['Zhang, Huan', 'Wang, Dang', 'Zhong, Huijuan', 'Luo, Rui', 'Shang, Min', 'Liu, Dezhi', 'Chen, Huanchun', 'Fang, Liurong', 'Xiao, Shaobo']",Sci Rep,,,True
0f27c25599e793f5628c7d8519eeaabbf7887ca2,PMC,Ubiquitin-specific Protease 15 Negatively Regulates Virus-induced Type I Interferon Signaling via Catalytically-dependent and -independent Mechanisms,http://dx.doi.org/10.1038/srep11220,PMC4650652,26061460,CC BY,"Viral infection triggers a series of signaling cascades, which converge to activate the transcription factors nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3), thereby inducing the transcription of type I interferons (IFNs). Although not fully characterized, these innate antiviral responses are fine-tuned by dynamic ubiquitination and deubiquitination processes. In this study, we report ubiquitin-specific protease (USP) 15 is involved in regulation of the retinoic acid-inducible gene I (RIG-I)-dependent type I IFN induction pathway. Knockdown of endogenous USP15 augmented cellular antiviral responses. Overexpression of USP15 inhibited the transcription of IFN-β. Further analyses identified histidine 862 as a critical residue for USP15’s catalytic activity. Interestingly, USP15 specifically removed lysine 63-linked polyubiquitin chains from RIG-I among the essential components in RIG-I-like receptor-dependent pathway. In addition, we demonstrated that in contrast to USP15 de-ubiquitinating (DUB) activity, USP15-mediated inhibition of IFN signaling was not abolished by mutations eliminating the catalytic activity, indicating that a fraction of USP15-mediated IFN antagonism was independent of the DUB activity. Catalytically inactive USP15 mutants, as did the wild-type protein, disrupted virus-induced interaction of RIG-I and IFN-β promoter stimulator 1. Taken together, our data demonstrate that USP15 acts as a negative regulator of RIG-I signaling via DUB-dependent and independent mechanisms.",2015 Jun 10,"['Zhang, Huan', 'Wang, Dang', 'Zhong, Huijuan', 'Luo, Rui', 'Shang, Min', 'Liu, Dezhi', 'Chen, Huanchun', 'Fang, Liurong', 'Xiao, Shaobo']",Sci Rep,,,False
19ddf65d65d5e172ac3ceda4662b68769633dbe6,PMC,Dynamics of Multi-stage Infections on Networks,http://dx.doi.org/10.1007/s11538-015-0109-1,PMC4651987,26403422,CC BY,"This paper investigates the dynamics of infectious diseases with a non-exponentially distributed infectious period. This is achieved by considering a multi-stage infection model on networks. Using pairwise approximation with a standard closure, a number of important characteristics of disease dynamics are derived analytically, including the final size of an epidemic and a threshold for epidemic outbreaks, and it is shown how these quantities depend on disease characteristics, as well as the number of disease stages. Stochastic simulations of dynamics on networks are performed and compared to output of pairwise models for several realistic examples of infectious diseases to illustrate the role played by the number of stages in the disease dynamics. These results show that a higher number of disease stages results in faster epidemic outbreaks with a higher peak prevalence and a larger final size of the epidemic. The agreement between the pairwise and simulation models is excellent in the cases we consider.",2015 Sep 24,"['Sherborne, N.', 'Blyuss, K. B.', 'Kiss, I. Z.']",Bull Math Biol,,,True
1edab5890fbff22ad353739d3d1e80a86d482820,PMC,"Handwashing with soap and national handwashing projects in Korea: focus on the National Handwashing Survey, 2006-2014",http://dx.doi.org/10.4178/epih/e2015039,PMC4652062,26725224,CC BY,"OBJECTIVES: Handwashing is the most fundamental way to prevent the spread of infectious diseases. Correct handwashing can prevent 50 to 70% of water-infections and foodborne-infections. We report the results of a fact-finding study on general handwashing attitude and practice in the Republic of Korea by analyzing habits and awareness among adults and students (grades 4 to 12) based on the 2006 to 2014 National Handwashing Surveys and observational surveys. METHODS: The awareness survey was performed by telephone interviews with adults and students in 16 municipalities and provinces sampled by quota for region, sex and age. The observational survey was performed in subway, railway, and other public restrooms in seven municipalities selected through systematic sampling. RESULTS: Adults and students washed their hands with soap/sanitizer an average of 6.6 and 5.2 times daily, respectively, in 2014, an increase and decrease compared to 2006 (4.8) and 2013 (6.8). Their average daily handwashing frequency in 2014, 9.8 and 8.3, was higher than in 2006 (7.6), but lower than in 2013 (10.3).The percentage of participants handwashing with soap after using the restroom (29.5%) has been increasing since 2009, but remain slower than in other countries (42% to 49%). The percentages of participants handwashing with water in 2014, 2013, and 2011 were 57.5%, 72.6%, and 71.4%, respectively. CONCLUSIONS: Handwashing with soap is an important national public health issue, and national projects promoting it should be given high priority. Research support is necessary to provide scientific evidence of the importance of handwashing with soap and to develop and implement evidence-based policies.",2015 Aug 31,"['Lee, Moo-Sik', 'Hong, Su Jin', 'Kim, Young-Taek']",Epidemiol Health,,,True
1505b1491459e5a9d560f06da7c48ae278bc48bc,PMC,"Handwashing with soap and national handwashing projects in Korea: focus on the National Handwashing Survey, 2006-2014",http://dx.doi.org/10.4178/epih/e2015039,PMC4652062,26725224,CC BY,"OBJECTIVES: Handwashing is the most fundamental way to prevent the spread of infectious diseases. Correct handwashing can prevent 50 to 70% of water-infections and foodborne-infections. We report the results of a fact-finding study on general handwashing attitude and practice in the Republic of Korea by analyzing habits and awareness among adults and students (grades 4 to 12) based on the 2006 to 2014 National Handwashing Surveys and observational surveys. METHODS: The awareness survey was performed by telephone interviews with adults and students in 16 municipalities and provinces sampled by quota for region, sex and age. The observational survey was performed in subway, railway, and other public restrooms in seven municipalities selected through systematic sampling. RESULTS: Adults and students washed their hands with soap/sanitizer an average of 6.6 and 5.2 times daily, respectively, in 2014, an increase and decrease compared to 2006 (4.8) and 2013 (6.8). Their average daily handwashing frequency in 2014, 9.8 and 8.3, was higher than in 2006 (7.6), but lower than in 2013 (10.3).The percentage of participants handwashing with soap after using the restroom (29.5%) has been increasing since 2009, but remain slower than in other countries (42% to 49%). The percentages of participants handwashing with water in 2014, 2013, and 2011 were 57.5%, 72.6%, and 71.4%, respectively. CONCLUSIONS: Handwashing with soap is an important national public health issue, and national projects promoting it should be given high priority. Research support is necessary to provide scientific evidence of the importance of handwashing with soap and to develop and implement evidence-based policies.",2015 Aug 31,"['Lee, Moo-Sik', 'Hong, Su Jin', 'Kim, Young-Taek']",Epidemiol Health,,,False
55b3d85d69f463bf877361addcaba605014f2231,PMC,Epidemiologic features of the first MERS outbreak in Korea: focus on Pyeongtaek St. Mary’s Hospital,http://dx.doi.org/10.4178/epih/e2015041,PMC4652064,26725225,CC BY,"OBJECTIVES: This study investigated the epidemiologic features of the confirmed cases of Middle East Respiratory Syndrome (MERS) in Pyeongtaek St. Mary’s Hospital, where the outbreak first began, in order to identify lessons relevant for the prevention and control of future outbreaks. METHODS: The patients’ clinical symptoms and test results were collected from their medical records. The caregivers of patients were identified by phone calls. RESULTS: After patient zero (case #1) was admitted to Pyeongtaek St. Mary’s Hospital (May 15-May 17), an outbreak occurred, with 36 cases between May 18 and June 4, 2015. Six patients died (fatality rate, 16.7%). Twenty-six cases occurred in the first-generation, and 10 in the second-generation. The median incubation period was five days, while the median period from symptom onset to death was 12.5 days. While the total attack rate was 3.9%, the attack rate among inpatients was 7.6%, and the inpatients on the eighth floor, where patient zero was hospitalized, had an 18.6% attack rate. In contrast, caregivers and medical staff showed attack rates of 3.3% and 1.1%, respectively. CONCLUSIONS: The attack rates were higher than those of the previous outbreaks in other countries. The outbreak spread beyond Pyeongtaek St. Mary’s Hospital when four of the patients were moved to other hospitals without appropriate quarantine. The best method of preventing future outbreaks is to overcome the vulnerabilities observed in this outbreak, such as ward crowding, patient migration without appropriate data sharing, and the lack of an initial broad quarantine.",2015 Sep 17,"['Kim, Kyung Min', 'Ki, Moran', 'Cho, Sung-il', 'Sung, Minki', 'Hong, Jin Kwan', 'Cheong, Hae-Kwan', 'Kim, Jong-Hun', 'Lee, Sang-Eun', 'Lee, Changhwan', 'Lee, Keon-Joo', 'Park, Yong-Shik', 'Kim, Seung Woo', 'Choi, Bo Youl']",Epidemiol Health,,,True
ed5d3f1db5936c2b86eb9ea46eab96a0b67a124e,PMC,Epidemiologic features of the first MERS outbreak in Korea: focus on Pyeongtaek St. Mary’s Hospital,http://dx.doi.org/10.4178/epih/e2015041,PMC4652064,26725225,CC BY,"OBJECTIVES: This study investigated the epidemiologic features of the confirmed cases of Middle East Respiratory Syndrome (MERS) in Pyeongtaek St. Mary’s Hospital, where the outbreak first began, in order to identify lessons relevant for the prevention and control of future outbreaks. METHODS: The patients’ clinical symptoms and test results were collected from their medical records. The caregivers of patients were identified by phone calls. RESULTS: After patient zero (case #1) was admitted to Pyeongtaek St. Mary’s Hospital (May 15-May 17), an outbreak occurred, with 36 cases between May 18 and June 4, 2015. Six patients died (fatality rate, 16.7%). Twenty-six cases occurred in the first-generation, and 10 in the second-generation. The median incubation period was five days, while the median period from symptom onset to death was 12.5 days. While the total attack rate was 3.9%, the attack rate among inpatients was 7.6%, and the inpatients on the eighth floor, where patient zero was hospitalized, had an 18.6% attack rate. In contrast, caregivers and medical staff showed attack rates of 3.3% and 1.1%, respectively. CONCLUSIONS: The attack rates were higher than those of the previous outbreaks in other countries. The outbreak spread beyond Pyeongtaek St. Mary’s Hospital when four of the patients were moved to other hospitals without appropriate quarantine. The best method of preventing future outbreaks is to overcome the vulnerabilities observed in this outbreak, such as ward crowding, patient migration without appropriate data sharing, and the lack of an initial broad quarantine.",2015 Sep 17,"['Kim, Kyung Min', 'Ki, Moran', 'Cho, Sung-il', 'Sung, Minki', 'Hong, Jin Kwan', 'Cheong, Hae-Kwan', 'Kim, Jong-Hun', 'Lee, Sang-Eun', 'Lee, Changhwan', 'Lee, Keon-Joo', 'Park, Yong-Shik', 'Kim, Seung Woo', 'Choi, Bo Youl']",Epidemiol Health,,,True
8923bae528dc7e9ed10fbb6e823707dd1018be9d,PMC,Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. actinidiae,http://dx.doi.org/10.1038/srep16961,PMC4652207,26581656,CC BY,"Normalization of data, by choosing the appropriate reference genes (RGs), is fundamental for obtaining reliable results in reverse transcription-quantitative PCR (RT-qPCR). In this study, we assessed Actinidia deliciosa leaves inoculated with two doses of Pseudomonas syringae pv. actinidiae during a period of 13 days for the expression profile of nine candidate RGs. Their expression stability was calculated using four algorithms: geNorm, NormFinder, BestKeeper and the deltaCt method. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and protein phosphatase 2A (PP2A) were the most stable genes, while β-tubulin and 7s-globulin were the less stable. Expression analysis of three target genes, chosen for RGs validation, encoding the reactive oxygen species scavenging enzymes ascorbate peroxidase (APX), superoxide dismutase (SOD) and catalase (CAT) indicated that a combination of stable RGs, such as GAPDH and PP2A, can lead to an accurate quantification of the expression levels of such target genes. The APX level varied during the experiment time course and according to the inoculum doses, whereas both SOD and CAT resulted down-regulated during the first four days, and up-regulated afterwards, irrespective of inoculum dose. These results can be useful for better elucidating the molecular interaction in the A. deliciosa/P. s. pv. actinidiae pathosystem and for RGs selection in bacteria-plant pathosystems.",2015 Nov 19,"['Petriccione, Milena', 'Mastrobuoni, Francesco', 'Zampella, Luigi', 'Scortichini, Marco']",Sci Rep,,,True
0e5168af60cc8a258ea92c0a87f4ae16f235c7c9,PMC,NK cells in asthma exacerbation,,PMC4652962,26296976,CC BY,,2015 Jul 8,"['Lunding, Lars', 'Wegmann, Michael']",Oncotarget,,,False
28fbe1da18bb4a2e0f8a42013e14794b6f3038f4,PMC,"Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol",http://dx.doi.org/10.1186/s40064-015-1490-9,PMC4653124,26618098,CC BY,"As of September 30, 2015, a total of 1589 laboratory-confirmed cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization (WHO). At present there is no effective specific therapy against MERS-CoV. The use of convalescent plasma (CP) has been suggested as a potential therapy based on existing evidence from other viral infections. We aim to study the feasibility of CP therapy as well as its safety and clinical and laboratory effects in critically ill patients with MERS-CoV infection. We will also examine the pharmacokinetics of the MERS-CoV antibody response and viral load over the course of MERS-CoV infection. This study will inform a future randomized controlled trial that will examine the efficacy of CP therapy for MERS-CoV infection. In the CP collection phase, potential donors will be tested by the enzyme linked immunosorbent assay (ELISA) and the indirect fluorescent antibody (IFA) techniques for the presence of anti-MERS-CoV antibodies. Subjects with anti-MERS-CoV IFA titer of ≥1:160 and no clinical or laboratory evidence of MERS-CoV infection will be screened for eligibility for plasma donation according to standard donation criteria. In the CP therapy phase, 20 consecutive critically ill patients admitted to intensive care unit with laboratory-confirmed MERS-CoV infection will be enrolled and each will receive 2 units of CP. Post enrollment, patients will be followed for clinical and laboratory outcomes that include anti-MERS-CoV antibodies and viral load. This protocol was developed collaboratively by King Abdullah International Medical Research Center (KAIMRC), Gulf Cooperation Council (GCC) Infection Control Center Group and the World Health Organization—International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO) MERS-CoV Working Group. It was approved in June 2014 by the Ministry of the National Guard Health Affairs Institutional Review Board (IRB). A data safety monitoring board (DSMB) was formulated. The study is registered at http://www.clinicaltrials.gov (NCT02190799).",2015 Nov 19,"['Arabi, Yaseen', 'Balkhy, Hanan', 'Hajeer, Ali H.', 'Bouchama, Abderrezak', 'Hayden, Frederick G.', 'Al-Omari, Awad', 'Al-Hameed, Fahad M.', 'Taha, Yusri', 'Shindo, Nahoko', 'Whitehead, John', 'Merson, Laura', 'AlJohani, Sameera', 'Al-Khairy, Khalid', 'Carson, Gail', 'Luke, Thomas C.', 'Hensley, Lisa', 'Al-Dawood, Abdulaziz', 'Al-Qahtani, Saad', 'Modjarrad, Kayvon', 'Sadat, Musharaf', 'Rohde, Gernot', 'Leport, Catherine', 'Fowler, Robert']",Springerplus,,,True
717168e782bf72b65add057c1cebe8d1bfdffbda,PMC,Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments,http://dx.doi.org/10.1371/journal.ppat.1005274,PMC4654589,26587836,CC BY,"Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus associated with various AIDS-related malignancies. Like other herpesviruses, multiple processes required for KSHV lytic replication, including viral transcription, viral DNA synthesis and capsid assembly occur in virus-induced intranuclear structures, termed replication and transcription compartments (RTCs). Here we utilised a novel methodology, combining subcellular fractionation and quantitative proteomics, to identify cellular proteins which are recruited to KSHV-induced RTCs and thus play a key role in KSHV lytic replication. We show that several isoforms of the HSP70 chaperone family, Hsc70 and iHsp70, are redistributed from the cytoplasm into the nucleus coinciding with the initial formation of KSHV-induced RTCs. We demonstrate that nuclear chaperone foci are dynamic, initially forming adjacent to newly formed KSHV RTCs, however during later time points the chaperones move within KSHV RTCs and completely co-localise with actively replicating viral DNA. The functional significance of Hsp70 isoforms recruitment into KSHV RTCs was also examined using the specific Hsp70 isoform small molecule inhibitor, VER-155008. Intriguingly, results highlight an essential role of Hsp70 isoforms in the KSHV replication cycle independent of protein stability and maturation. Notably, inhibition of Hsp70 isoforms precluded KSHV RTC formation and RNA polymerase II (RNAPII) relocalisation to the viral genome leading to the abolishment of global KSHV transcription and subsequent viral protein synthesis and DNA replication. These new findings have revealed novel mechanisms that regulate KSHV lytic replication and highlight the potential of HSP70 inhibitors as novel antiviral agents.",2015 Nov 20,"['Baquero-Pérez, Belinda', 'Whitehouse, Adrian']",PLoS Pathog,,,True
00a991c7d1c8a86b5627340206fa83d6716f34c1,PMC,Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments,http://dx.doi.org/10.1371/journal.ppat.1005274,PMC4654589,26587836,CC BY,"Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus associated with various AIDS-related malignancies. Like other herpesviruses, multiple processes required for KSHV lytic replication, including viral transcription, viral DNA synthesis and capsid assembly occur in virus-induced intranuclear structures, termed replication and transcription compartments (RTCs). Here we utilised a novel methodology, combining subcellular fractionation and quantitative proteomics, to identify cellular proteins which are recruited to KSHV-induced RTCs and thus play a key role in KSHV lytic replication. We show that several isoforms of the HSP70 chaperone family, Hsc70 and iHsp70, are redistributed from the cytoplasm into the nucleus coinciding with the initial formation of KSHV-induced RTCs. We demonstrate that nuclear chaperone foci are dynamic, initially forming adjacent to newly formed KSHV RTCs, however during later time points the chaperones move within KSHV RTCs and completely co-localise with actively replicating viral DNA. The functional significance of Hsp70 isoforms recruitment into KSHV RTCs was also examined using the specific Hsp70 isoform small molecule inhibitor, VER-155008. Intriguingly, results highlight an essential role of Hsp70 isoforms in the KSHV replication cycle independent of protein stability and maturation. Notably, inhibition of Hsp70 isoforms precluded KSHV RTC formation and RNA polymerase II (RNAPII) relocalisation to the viral genome leading to the abolishment of global KSHV transcription and subsequent viral protein synthesis and DNA replication. These new findings have revealed novel mechanisms that regulate KSHV lytic replication and highlight the potential of HSP70 inhibitors as novel antiviral agents.",2015 Nov 20,"['Baquero-Pérez, Belinda', 'Whitehouse, Adrian']",PLoS Pathog,,,False
6ca67aad56774445edd862e8c6ac12bc38673278,PMC,Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments,http://dx.doi.org/10.1371/journal.ppat.1005274,PMC4654589,26587836,CC BY,"Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus associated with various AIDS-related malignancies. Like other herpesviruses, multiple processes required for KSHV lytic replication, including viral transcription, viral DNA synthesis and capsid assembly occur in virus-induced intranuclear structures, termed replication and transcription compartments (RTCs). Here we utilised a novel methodology, combining subcellular fractionation and quantitative proteomics, to identify cellular proteins which are recruited to KSHV-induced RTCs and thus play a key role in KSHV lytic replication. We show that several isoforms of the HSP70 chaperone family, Hsc70 and iHsp70, are redistributed from the cytoplasm into the nucleus coinciding with the initial formation of KSHV-induced RTCs. We demonstrate that nuclear chaperone foci are dynamic, initially forming adjacent to newly formed KSHV RTCs, however during later time points the chaperones move within KSHV RTCs and completely co-localise with actively replicating viral DNA. The functional significance of Hsp70 isoforms recruitment into KSHV RTCs was also examined using the specific Hsp70 isoform small molecule inhibitor, VER-155008. Intriguingly, results highlight an essential role of Hsp70 isoforms in the KSHV replication cycle independent of protein stability and maturation. Notably, inhibition of Hsp70 isoforms precluded KSHV RTC formation and RNA polymerase II (RNAPII) relocalisation to the viral genome leading to the abolishment of global KSHV transcription and subsequent viral protein synthesis and DNA replication. These new findings have revealed novel mechanisms that regulate KSHV lytic replication and highlight the potential of HSP70 inhibitors as novel antiviral agents.",2015 Nov 20,"['Baquero-Pérez, Belinda', 'Whitehouse, Adrian']",PLoS Pathog,,,False
9f75752eb62482a4e2919951414267f541e419db,PMC,Experimental infection of a US spike-insertion deletion porcine epidemic diarrhea virus in conventional nursing piglets and cross-protection to the original US PEDV infection,http://dx.doi.org/10.1186/s13567-015-0278-9,PMC4654902,26589292,CC BY,"Although the original US porcine epidemic diarrhea virus (PEDV) was confirmed as highly virulent by multiple studies, the virulence of spike-insertion deletion (S-INDEL) PEDV strains is undefined. In this study, 3–4 day-old conventional suckling piglets were inoculated with S-INDEL PEDV Iowa106 (4 pig litters) to study its virulence. Two litters of age-matched piglets were inoculated with either the original US PEDV PC21A or mock as positive and negative controls, respectively. Subsequently, all pigs were challenged with the original US PEDV PC21A on 21–29 days post-inoculation (dpi) to assess cross-protection. All S-INDEL Iowa106- and the original US PC21A-inoculated piglets developed diarrhea. However, the severity of clinical signs, mortality (0–75%) and fecal PEDV RNA shedding titers varied among the four S-INDEL Iowa106-inoculated litters. Compared with the original PC21A, piglets euthanized/died acutely from S-INDEL Iowa106 infection had relatively milder villous atrophy, lower antigen scores and more limited intestinal infection. Two of four S-INDEL Iowa106-infected sows and the original PC21A-infected sow showed anorexia and watery diarrhea for 1–4 days. After the original PC21A challenge, a subset (13/16) of S-INDEL Iowa106-inoculated piglets developed diarrhea, whereas all (5/5) and no (0/4) pigs in the mock and original PC21A-inoculated pigs had diarrhea, respectively. Our results suggest that the virulence of S-INDEL PEDV Iowa106 was less than the original US PEDV PC21A in suckling pigs, with 100% morbidity and 18% (6/33) overall (0–75%) mortality in suckling pigs depending on factors such as the sow’s health and lactation and the piglets’ birth weight. Prior infection by S-INDEL Iowa106 provided partial cross-protection to piglets against the original PC21A challenge at 21–29 dpi.",2015 Nov 20,"['Lin, Chun-Ming', 'Annamalai, Thavamathi', 'Liu, Xinsheng', 'Gao, Xiang', 'Lu, Zhongyan', 'El-Tholoth, Mohamed', 'Hu, Hui', 'Saif, Linda J.', 'Wang, Qiuhong']",Vet Res,,,True
3065f9bd3f5cbaad08a1f0e35f5781ccd0857cd7,PMC,The influence of cold weather on the usage of emergency link calls: a case study in Hong Kong,http://dx.doi.org/10.1186/s12911-015-0191-1,PMC4654920,26590158,CC BY,"BACKGROUND: In response to an unexpected long cold spell in February 1996 which killed more than 100 older adults (mostly living alone) in Hong Kong, the Hong Kong Senior Citizen Home Safety Association established a Personal Emergency Link Service to provide emergency contact to the older adults, which uses a telephone system to render emergency relief and total care service around the clock. To facilitate the dynamic and efficient allocation of service resources, it is crucial to understand the factors linked with use of the services and number of hospital admissions arising from PE link service. METHODS: We initially use the Poisson generalized linear model (GLM) with polynomial effect functions of relevant covariates. If the time series of residuals from fitting the Poisson GLM reveals significant serial correlation, a Poisson generalized linear autoregressive moving average (GLARMA) model is refitted to the data to account for the auto-correlation among the time series of daily call numbers. If the data is overdispersed relative to the best fitting Poisson GLARMA model, then the negative binomial GLARMA model is refitted to account for any overdispersion. In all the models, dummy variables for weekdays and months are included to account for any cyclic trends due weekday effect or month of the year effect. The secular time trend is modeled by a polynomial function of calendar time over the study period. Finally any critical temperatures are identified by visually inspecting the graph of the effect function of temperature. RESULTS: The weekday and month effects are both significant with Monday seeing more PE Link calls than Sunday and June seeing less than January. Temperature has significant effect on the PE Link call rate with the effect highly nonlinear. A critical temperature, below which excessive increase in PE link calls that lead to hospital admissions, is identified to be around 15 °C. CONCLUSION: Identifying a threshold temperature which generates an excessive increase in the expected number of PE Link calls would be useful in service provision planning and support for elderly in need of hospital admission.",2015 Aug 13,"['Chen, Feng', 'Yip, Paul SF']",BMC Med Inform Decis Mak,,,True
8d5bf19e94a61fcf764faf3a9362f61e1fd2b90b,PMC,Rapid drop in the reproduction number during the Ebola outbreak in the Democratic Republic of Congo,http://dx.doi.org/10.7717/peerj.1418,PMC4655090,26618087,CC BY,"The Democratic Republic of Congo (DRC) experienced a confined rural outbreak of Ebola virus disease (EVD) with 69 reported cases from July to October 2014. Understanding the transmission dynamics during the outbreak can provide important information for anticipating and controlling future EVD epidemics. I fitted an EVD transmission model to previously published data of this outbreak and estimated the basic reproduction number R(0) = 5.2 (95% CI [4.0–6.7]). The model suggests that the net reproduction number R(t) fell below unity 28 days (95% CI [25–34] days) after the onset of symptoms in the index case. This study adds to previous epidemiological descriptions of the 2014 EVD outbreak in DRC, and is consistent with the notion that a rapid implementation of control interventions helped reduce further spread.",2015 Nov 19,"Althaus, Christian L.",PeerJ,,,False
173c216511cdf5174a09140aca928d1a83d8c916,PMC,Rapid drop in the reproduction number during the Ebola outbreak in the Democratic Republic of Congo,http://dx.doi.org/10.7717/peerj.1418,PMC4655090,26618087,CC BY,"The Democratic Republic of Congo (DRC) experienced a confined rural outbreak of Ebola virus disease (EVD) with 69 reported cases from July to October 2014. Understanding the transmission dynamics during the outbreak can provide important information for anticipating and controlling future EVD epidemics. I fitted an EVD transmission model to previously published data of this outbreak and estimated the basic reproduction number R(0) = 5.2 (95% CI [4.0–6.7]). The model suggests that the net reproduction number R(t) fell below unity 28 days (95% CI [25–34] days) after the onset of symptoms in the index case. This study adds to previous epidemiological descriptions of the 2014 EVD outbreak in DRC, and is consistent with the notion that a rapid implementation of control interventions helped reduce further spread.",2015 Nov 19,"Althaus, Christian L.",PeerJ,,,False
02bfb4c09489a5f48c23e8441e37b055bf7228ee,PMC,Chikungunya nsP2 protease is not a papain-like cysteine protease and the catalytic dyad cysteine is interchangeable with a proximal serine,http://dx.doi.org/10.1038/srep17125,PMC4657084,26597768,CC BY,"Chikungunya virus is the pathogenic alphavirus that causes chikungunya fever in humans. In the last decade millions of cases have been reported around the world from Africa to Asia to the Americas. The alphavirus nsP2 protein is multifunctional and is considered to be pivotal to viral replication, as the nsP2 protease activity is critical for proteolytic processing of the viral polyprotein during replication. Classically the alphavirus nsP2 protease is thought to be papain-like with the enzyme reaction proceeding through a cysteine/histidine catalytic dyad. We performed structure-function studies on the chikungunya nsP2 protease and show that the enzyme is not papain-like. Characterization of the catalytic dyad cysteine residue enabled us to identify a nearby serine that is catalytically interchangeable with the dyad cysteine residue. The enzyme retains activity upon alanine replacement of either residue but a replacement of both cysteine and serine residues results in no detectable activity. Protein dynamics appears to allow the use of either the cysteine or the serine residue in catalysis. This switchable dyad residue has not been previously reported for alphavirus nsP2 proteases and would have a major impact on the nsP2 protease as an anti-viral target.",2015 Nov 24,"['Saisawang, Chonticha', 'Saitornuang, Sawanan', 'Sillapee, Pornpan', 'Ubol, Sukathida', 'Smith, Duncan R.', 'Ketterman, Albert J.']",Sci Rep,,,True
458c9e598bc8757d58a592739384d70ae4560a50,PMC,Amelioration of Japanese encephalitis by blockage of 4-1BB signaling is coupled to divergent enhancement of type I/II IFN responses and Ly-6C(hi) monocyte differentiation,http://dx.doi.org/10.1186/s12974-015-0438-x,PMC4657197,26597582,CC BY,"BACKGROUND: Japanese encephalitis (JE), a neuroinflammation caused by zoonotic JE virus, is the major cause of viral encephalitis worldwide and poses an increasing threat to global health and welfare. To date, however, there has been no report describing the regulation of JE progression using immunomodulatory tools for developing therapeutic strategies. We tested whether blocking the 4-1BB signaling pathway would regulate JE progression using murine JE model. METHODS: Infected wild-type and 4-1BB-knockout (KO) mice were examined daily for mortality and clinical signs, and neuroinflammation in the CNS was evaluated by infiltration of inflammatory leukocytes and cytokine expression. In addition, viral burden, JEV-specific T cell, and type I/II IFN (IFN-I/II) innate responses were analyzed. RESULTS: Blocking the 4-1BB signaling pathway significantly increased resistance to JE and reduced viral burden in extraneural tissues and the CNS, rather than causing a detrimental effect. In addition, treatment with 4-1BB agonistic antibody exacerbated JE. Furthermore, JE amelioration and reduction of viral burden by blocking the 4-1BB signaling pathway were associated with an increased frequency of IFN-II-producing NK and CD4(+) Th1 cells as well as increased infiltration of mature Ly-6C(hi) monocytes in the inflamed CNS. More interestingly, DCs and macrophages derived from 4-1BB KO mice showed potent and rapid IFN-I innate immune responses upon JEV infection, which was coupled to strong induction of PRRs (RIG-I, MDA5), transcription factors (IRF7), and antiviral ISG genes (ISG49, ISG54, ISG56). Further, the ablation of 4-1BB signaling enhanced IFN-I innate responses in neuron cells, which likely regulated viral spread in the CNS. Finally, we confirmed that blocking the 4-1BB signaling pathway in myeloid cells derived from hematopoietic stem cells (HSCs) played a dominant role in ameliorating JE. In support of this finding, HSC-derived leukocytes played a dominant role in generating the IFN-I innate responses in the host. CONCLUSIONS: Blocking the 4-1BB signaling pathway ameliorates JE via divergent enhancement of IFN-II-producing NK and CD4(+) Th1 cells and mature Ly-6C(hi) monocyte infiltration, as well as an IFN-I innate response of myeloid-derived cells. Therefore, regulation of the 4-1BB signaling pathway with antibodies or inhibitors could be a valuable therapeutic strategy for the treatment of JE.",2015 Nov 24,"['Kim, Seong Bum', 'Choi, Jin Young', 'Kim, Jin Hyoung', 'Uyangaa, Erdenebelig', 'Patil, Ajit Mahadev', 'Park, Sang-Youel', 'Lee, John Hwa', 'Kim, Koanhoi', 'Han, Young Woo', 'Eo, Seong Kug']",J Neuroinflammation,,,True
36469337a42a7feb9bdefa958b364d2e269ec2ae,PMC,Rapid detection of the common avian leukosis virus subgroups by real-time loop-mediated isothermal amplification,http://dx.doi.org/10.1186/s12985-015-0430-1,PMC4657318,26596553,CC BY,"BACKGROUND: Subgroups A, B, E and J are the major subgroups of avian leukosis virus (ALV) infecting chickens. ALV infection has become endemic in China and has a significant negative effect on the poultry industry. Consequently, there is an urgent need for a specific, sensitive and rapid method for diagnosis and eradication of ALV. Therefore, we developed a simple and rapid real-time loop-mediated isothermal amplification (LAMP) reaction for the timely detection of the common ALV subgroups, whereby the amplification can be obtained in 35 min under isothermal conditions at 63 °C, ability to specific, sensitive and rapid detect all the common ALV subgroups. METHODS: A set of four specific primers was designed to target the sequences of the pol gene of ALV, and the loop-mediated isothermal amplification (LAMP) assay were developed and compared with PCR and virus isolation methods. RESULTS: The results from specificity of the LAMP assay showed that only target ALVs DNA was amplified. The LAMP assay demonstrated a sensitivity of 20 copies/reaction of ALV DNA, which was 10 times higher than the conventional PCR measurement. To further evaluate the reliability of the method, the assay was evaluated with ALV DNA from a panel of 81 clinical samples suspected of ALV infection. The results verify that the LAMP method was more sensitive than the conventional PCR and virus isolation method. CONCLUSION: In conclusion, the developed LAMP assay was a simple, inexpensive, sensitive method for the rapid detection of the most common subgroups of ALV, and it provided a useful and practical tool in the eradication program for ALV in the poultry industry.",2015 Nov 24,"['Peng, Hao', 'Qin, Lili', 'Bi, Yuyu', 'Wang, Peikun', 'Zou, Guangzhen', 'Li, Jun', 'Yang, Yongli', 'Zhong, Xingfu', 'Wei, Ping']",Virol J,,,True
a63d851872c31a91cf814a84fc2af7f4fb15ce3d,PMC,A parallel genome-wide RNAi screening strategy to identify host proteins important for entry of Marburg virus and H5N1 influenza virus,http://dx.doi.org/10.1186/s12985-015-0420-3,PMC4657351,26596270,CC BY,"BACKGROUND: Genome-wide RNAi screening has been widely used to identify host proteins involved in replication and infection of different viruses, and numerous host factors are implicated in the replication cycles of these viruses, demonstrating the power of this approach. However, discrepancies on target identification of the same viruses by different groups suggest that high throughput RNAi screening strategies need to be carefully designed, developed and optimized prior to the large scale screening. METHODS: Two genome-wide RNAi screens were performed in parallel against the entry of pseudotyped Marburg viruses and avian influenza virus H5N1 utilizing an HIV-1 based surrogate system, to identify host factors which are important for virus entry. A comparative analysis approach was employed in data analysis, which alleviated systematic positional effects and reduced the false positive number of virus-specific hits. RESULTS: The parallel nature of the strategy allows us to easily identify the host factors for a specific virus with a greatly reduced number of false positives in the initial screen, which is one of the major problems with high throughput screening. The power of this strategy is illustrated by a genome-wide RNAi screen for identifying the host factors important for Marburg virus and/or avian influenza virus H5N1 as described in this study. CONCLUSIONS: This strategy is particularly useful for highly pathogenic viruses since pseudotyping allows us to perform high throughput screens in the biosafety level 2 (BSL-2) containment instead of the BSL-3 or BSL-4 for the infectious viruses, with alleviated safety concerns. The screening strategy together with the unique comparative analysis approach makes the data more suitable for hit selection and enables us to identify virus-specific hits with a much lower false positive rate.",2015 Nov 24,"['Cheng, Han', 'Koning, Katie', 'O’Hearn, Aileen', 'Wang, Minxiu', 'Rumschlag-Booms, Emily', 'Varhegyi, Elizabeth', 'Rong, Lijun']",Virol J,,,True
0a4f344f96d5a21e3d0f33e199983738c37a1631,PMC,The Impact of Human Mobility on HIV Transmission in Kenya,http://dx.doi.org/10.1371/journal.pone.0142805,PMC4657931,26599277,CC BY,"Disease spreads as a result of people moving and coming in contact with each other. Thus the mobility patterns of individuals are crucial in understanding disease dynamics. Here we study the impact of human mobility on HIV transmission in different parts of Kenya. We build an SIR metapopulation model that incorporates the different regions within the country. We parameterise the model using census data, HIV data and mobile phone data adopted to track human mobility. We found that movement between different regions appears to have a relatively small overall effect on the total increase in HIV cases in Kenya. However, the most important consequence of movement patterns was transmission of the disease from high infection to low prevalence areas. Mobility slightly increases HIV incidence rates in regions with initially low HIV prevalences and slightly decreases incidences in regions with initially high HIV prevalence. We discuss how regional HIV models could be used in public-health planning. This paper is a first attempt to model spread of HIV using mobile phone data, and we also discuss limitations to the approach.",2015 Nov 24,"['Isdory, Augustino', 'Mureithi, Eunice W.', 'Sumpter, David J. T.']",PLoS One,,,True
6c4f3eeb65df5c4294024c37835fa5097dd604e7,PMC,The Impact of Human Mobility on HIV Transmission in Kenya,http://dx.doi.org/10.1371/journal.pone.0142805,PMC4657931,26599277,CC BY,"Disease spreads as a result of people moving and coming in contact with each other. Thus the mobility patterns of individuals are crucial in understanding disease dynamics. Here we study the impact of human mobility on HIV transmission in different parts of Kenya. We build an SIR metapopulation model that incorporates the different regions within the country. We parameterise the model using census data, HIV data and mobile phone data adopted to track human mobility. We found that movement between different regions appears to have a relatively small overall effect on the total increase in HIV cases in Kenya. However, the most important consequence of movement patterns was transmission of the disease from high infection to low prevalence areas. Mobility slightly increases HIV incidence rates in regions with initially low HIV prevalences and slightly decreases incidences in regions with initially high HIV prevalence. We discuss how regional HIV models could be used in public-health planning. This paper is a first attempt to model spread of HIV using mobile phone data, and we also discuss limitations to the approach.",2015 Nov 24,"['Isdory, Augustino', 'Mureithi, Eunice W.', 'Sumpter, David J. T.']",PLoS One,,,True
0a9983132b38156cea8ed9e4313d270120f2731e,PMC,The Impact of Human Mobility on HIV Transmission in Kenya,http://dx.doi.org/10.1371/journal.pone.0142805,PMC4657931,26599277,CC BY,"Disease spreads as a result of people moving and coming in contact with each other. Thus the mobility patterns of individuals are crucial in understanding disease dynamics. Here we study the impact of human mobility on HIV transmission in different parts of Kenya. We build an SIR metapopulation model that incorporates the different regions within the country. We parameterise the model using census data, HIV data and mobile phone data adopted to track human mobility. We found that movement between different regions appears to have a relatively small overall effect on the total increase in HIV cases in Kenya. However, the most important consequence of movement patterns was transmission of the disease from high infection to low prevalence areas. Mobility slightly increases HIV incidence rates in regions with initially low HIV prevalences and slightly decreases incidences in regions with initially high HIV prevalence. We discuss how regional HIV models could be used in public-health planning. This paper is a first attempt to model spread of HIV using mobile phone data, and we also discuss limitations to the approach.",2015 Nov 24,"['Isdory, Augustino', 'Mureithi, Eunice W.', 'Sumpter, David J. T.']",PLoS One,,,False
678b0f0a0a510ad2dc7a7c9ab6677172168094d0,PMC,The Impact of Human Mobility on HIV Transmission in Kenya,http://dx.doi.org/10.1371/journal.pone.0142805,PMC4657931,26599277,CC BY,"Disease spreads as a result of people moving and coming in contact with each other. Thus the mobility patterns of individuals are crucial in understanding disease dynamics. Here we study the impact of human mobility on HIV transmission in different parts of Kenya. We build an SIR metapopulation model that incorporates the different regions within the country. We parameterise the model using census data, HIV data and mobile phone data adopted to track human mobility. We found that movement between different regions appears to have a relatively small overall effect on the total increase in HIV cases in Kenya. However, the most important consequence of movement patterns was transmission of the disease from high infection to low prevalence areas. Mobility slightly increases HIV incidence rates in regions with initially low HIV prevalences and slightly decreases incidences in regions with initially high HIV prevalence. We discuss how regional HIV models could be used in public-health planning. This paper is a first attempt to model spread of HIV using mobile phone data, and we also discuss limitations to the approach.",2015 Nov 24,"['Isdory, Augustino', 'Mureithi, Eunice W.', 'Sumpter, David J. T.']",PLoS One,,,False
da15b43c189e131680b837f08b9df2137739d874,PMC,The Impact of Human Mobility on HIV Transmission in Kenya,http://dx.doi.org/10.1371/journal.pone.0142805,PMC4657931,26599277,CC BY,"Disease spreads as a result of people moving and coming in contact with each other. Thus the mobility patterns of individuals are crucial in understanding disease dynamics. Here we study the impact of human mobility on HIV transmission in different parts of Kenya. We build an SIR metapopulation model that incorporates the different regions within the country. We parameterise the model using census data, HIV data and mobile phone data adopted to track human mobility. We found that movement between different regions appears to have a relatively small overall effect on the total increase in HIV cases in Kenya. However, the most important consequence of movement patterns was transmission of the disease from high infection to low prevalence areas. Mobility slightly increases HIV incidence rates in regions with initially low HIV prevalences and slightly decreases incidences in regions with initially high HIV prevalence. We discuss how regional HIV models could be used in public-health planning. This paper is a first attempt to model spread of HIV using mobile phone data, and we also discuss limitations to the approach.",2015 Nov 24,"['Isdory, Augustino', 'Mureithi, Eunice W.', 'Sumpter, David J. T.']",PLoS One,,,False
d7c55372bf569553c20217248e0ca3260ff007cf,PMC,The Impact of Human Mobility on HIV Transmission in Kenya,http://dx.doi.org/10.1371/journal.pone.0142805,PMC4657931,26599277,CC BY,"Disease spreads as a result of people moving and coming in contact with each other. Thus the mobility patterns of individuals are crucial in understanding disease dynamics. Here we study the impact of human mobility on HIV transmission in different parts of Kenya. We build an SIR metapopulation model that incorporates the different regions within the country. We parameterise the model using census data, HIV data and mobile phone data adopted to track human mobility. We found that movement between different regions appears to have a relatively small overall effect on the total increase in HIV cases in Kenya. However, the most important consequence of movement patterns was transmission of the disease from high infection to low prevalence areas. Mobility slightly increases HIV incidence rates in regions with initially low HIV prevalences and slightly decreases incidences in regions with initially high HIV prevalence. We discuss how regional HIV models could be used in public-health planning. This paper is a first attempt to model spread of HIV using mobile phone data, and we also discuss limitations to the approach.",2015 Nov 24,"['Isdory, Augustino', 'Mureithi, Eunice W.', 'Sumpter, David J. T.']",PLoS One,,,False
90f28a7925b8350d3a484cac6ed454a328d08b67,PMC,Epidemiology of Enterovirus D68 in Ontario,http://dx.doi.org/10.1371/journal.pone.0142841,PMC4658075,26599365,CC BY,"In August 2014, children’s hospitals in Kansas City, Missouri and Chicago, Illinois notified the Centers for Disease Control and Prevention (CDC) about increased numbers of pediatric patients hospitalized with severe respiratory illness (SRI). In response to CDC reports, Public Health Ontario Laboratories (PHOL) launched an investigation of patients being tested for enterovirus D-68 (EV-D68) in Ontario, Canada. The purpose of this investigation was to enhance our understanding of EV-D68 epidemiology and clinical features. Data for this study included specimens submitted for EV-D68 testing at PHOL from September 1, 2014 to October 31, 2014. Comparisons were made between patients who tested positive for the virus (cases) and those testing negative (controls). EV-D68 was identified in 153/907 (16.8%) of patients tested. In the logistic regression model adjusting for age, sex, setting and time to specimen collection, individuals younger than 20 years of age were more likely to be diagnosed with EV-D68 compared to those 20 and over, with peak positivity at ages 5–9 years. Cases were not more likely to be hospitalized than controls. Cases were more likely to be identified in September than October (OR 8.07; 95% CI 5.15 to 12.64). Routine viral culture and multiplex PCR were inadequate methods to identify EV-D68 due to poor sensitivity and inability to differentiate EV-D68 from other enterovirus serotypes or rhinovirus. Testing for EV-D68 in Ontario from July to December, 2014 detected the presence of EV-D68 virus among young children during September-October, 2014, with most cases detected in September. There was no difference in hospitalization status between cases and controls. In order to better understand the epidemiology of this virus, surveillance for EV-D68 should include testing of symptomatic individuals from all treatment settings and patient age groups, with collection and analysis of comprehensive clinical and epidemiological data.",2015 Nov 23,"['Peci, Adriana', 'Winter, Anne-Luise', 'Warshawsky, Bryna', 'Booth, Tim F.', 'Eshaghi, AliReza', 'Li, Aimin', 'Perusini, Stephen', 'Olsha, Romy', 'Marchand-Austin, Alex', 'Kristjanson, Erik', 'Gubbay, Jonathan B.']",PLoS One,,,True
96c1bc8e891b94c919d20cd97d00b3790fc6d2b3,PMC,Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage,http://dx.doi.org/10.1016/j.immuni.2015.10.013,PMC4658338,26588782,CC BY,"Tissue damage caused by viral hepatitis is a major cause of morbidity and mortality worldwide. Using a mouse model of viral hepatitis, we identified virus-induced early transcriptional changes in the redox pathways in the liver, including downregulation of superoxide dismutase 1 (Sod1). Sod1(−/−) mice exhibited increased inflammation and aggravated liver damage upon viral infection, which was independent of T and NK cells and could be ameliorated by antioxidant treatment. Type I interferon (IFN-I) led to a downregulation of Sod1 and caused oxidative liver damage in Sod1(−/−) and wild-type mice. Genetic and pharmacological ablation of the IFN-I signaling pathway protected against virus-induced liver damage. These results delineate IFN-I mediated oxidative stress as a key mediator of virus-induced liver damage and describe a mechanism of innate-immunity-driven pathology, linking IFN-I signaling with antioxidant host defense and infection-associated tissue damage. VIDEO ABSTRACT:",2015 Nov 17,"['Bhattacharya, Anannya', 'Hegazy, Ahmed\xa0N.', 'Deigendesch, Nikolaus', 'Kosack, Lindsay', 'Cupovic, Jovana', 'Kandasamy, Richard\xa0K.', 'Hildebrandt, Andrea', 'Merkler, Doron', 'Kühl, Anja\xa0A.', 'Vilagos, Bojan', 'Schliehe, Christopher', 'Panse, Isabel', 'Khamina, Kseniya', 'Baazim, Hatoon', 'Arnold, Isabelle', 'Flatz, Lukas', 'Xu, Haifeng\xa0C.', 'Lang, Philipp\xa0A.', 'Aderem, Alan', 'Takaoka, Akinori', 'Superti-Furga, Giulio', 'Colinge, Jacques', 'Ludewig, Burkhard', 'Löhning, Max', 'Bergthaler, Andreas']",Immunity,,,False
2034ca5a9941b6e3d8b0ba9280a5b2fae192778d,PMC,Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage,http://dx.doi.org/10.1016/j.immuni.2015.10.013,PMC4658338,26588782,CC BY,"Tissue damage caused by viral hepatitis is a major cause of morbidity and mortality worldwide. Using a mouse model of viral hepatitis, we identified virus-induced early transcriptional changes in the redox pathways in the liver, including downregulation of superoxide dismutase 1 (Sod1). Sod1(−/−) mice exhibited increased inflammation and aggravated liver damage upon viral infection, which was independent of T and NK cells and could be ameliorated by antioxidant treatment. Type I interferon (IFN-I) led to a downregulation of Sod1 and caused oxidative liver damage in Sod1(−/−) and wild-type mice. Genetic and pharmacological ablation of the IFN-I signaling pathway protected against virus-induced liver damage. These results delineate IFN-I mediated oxidative stress as a key mediator of virus-induced liver damage and describe a mechanism of innate-immunity-driven pathology, linking IFN-I signaling with antioxidant host defense and infection-associated tissue damage. VIDEO ABSTRACT:",2015 Nov 17,"['Bhattacharya, Anannya', 'Hegazy, Ahmed\xa0N.', 'Deigendesch, Nikolaus', 'Kosack, Lindsay', 'Cupovic, Jovana', 'Kandasamy, Richard\xa0K.', 'Hildebrandt, Andrea', 'Merkler, Doron', 'Kühl, Anja\xa0A.', 'Vilagos, Bojan', 'Schliehe, Christopher', 'Panse, Isabel', 'Khamina, Kseniya', 'Baazim, Hatoon', 'Arnold, Isabelle', 'Flatz, Lukas', 'Xu, Haifeng\xa0C.', 'Lang, Philipp\xa0A.', 'Aderem, Alan', 'Takaoka, Akinori', 'Superti-Furga, Giulio', 'Colinge, Jacques', 'Ludewig, Burkhard', 'Löhning, Max', 'Bergthaler, Andreas']",Immunity,,,True
dde2f725f681ca3d6af28e816b5b58db9fe56551,PMC,"Social support and HIV/STDs infections among a probability-based sample of rural married migrant women in Shandong Province, China",http://dx.doi.org/10.1186/s12889-015-2508-5,PMC4658759,26603036,CC BY,"BACKGROUND: The increasing population of marriage-based migrant women is disproportionally affected by AIDS/STDs in China, and social support plays a critical role. This study aims to describe the social support level received by married migrant women in rural areas in Shandong province in comparison to non-migrant local women, identifies the relevant factors of this social support condition among married migrant women, and observes the correlation between social support level and infection status of AIDS and STDs among this group. METHODS: A probability-based sample of 1,076 migrant and 1,195 local women were included in the study. A pre-tested field questionnaire was administered to participants through a direct face-to-face interview. Questionnaire contained questions on socio-demographic information, AIDS and STDs prevalence information and Social Support Rating Scale (SSRS) which measures objective support, subjective support, and utilization of social support. RESULTS: Compared to local women, married migrant women had lower levels of social support in most dimensions. Multi-variable analysis revealed that relationship with spouse, family average income, number of children, education, engagement and claimed reasons of moving have various correlations with one or all dimensions of social support scores. Higher social support is also related to awareness of infection status of HIV and STDs among this group. CONCLUSION: Our findings provide further evidence that married migrant women have lower levels of social support which may be related to some social characteristics and their awareness status of AIDS and STDs infection status and that targeted interventions need to be developed for this population.",2015 Nov 24,"['Ma, Wenkang', 'Kang, Dianmin', 'Song, Yapei', 'Wei, Chongyi', 'Marley, Gifty', 'Ma, Wei']",BMC Public Health,,,True
4b130b88bd3514c7159a9c25c0f52e4a531950e5,PMC,Changes in microbiota during experimental human Rhinovirus infection,http://dx.doi.org/10.1186/s12879-015-1081-y,PMC4659412,26271750,CC BY,"BACKGROUND: Human Rhinovirus (HRV) is responsible for the majority of common colds and is frequently accompanied by secondary bacterial infections through poorly understood mechanisms. We investigated the effects of experimental human HRV serotype 16 infection on the upper respiratory tract microbiota. METHODS: Six healthy volunteers were infected with HRV16. We performed 16S ribosomal RNA-targeted pyrosequencing on throat swabs taken prior, during and after infection. We compared overall community diversity, phylogenetic structure of the ecosystem and relative abundances of the different bacteria between time points. RESULTS: During acute infection strong trends towards increases in the relative abundances of Haemophilus parainfluenzae and Neisseria subflava were observed, as well as a weaker trend towards increases of Staphylococcus aureus. No major differences were observed between day-1 and day 60, whereas differences between subjects were very high. CONCLUSIONS: HRV16 infection is associated with the increase of three genera known to be associated with secondary infections following HRV infections. The observed changes of upper respiratory tract microbiota could help explain why HRV infection predisposes to bacterial otitis media, sinusitis and pneumonia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1081-y) contains supplementary material, which is available to authorized users.",2015 Aug 14,"['Hofstra, J. J.', 'Matamoros, S.', 'van de Pol, M. A.', 'de Wever, B.', 'Tanck, M. W.', 'Wendt-Knol, H.', 'Deijs, M.', 'van der Hoek, L.', 'Wolthers, K. C.', 'Molenkamp, R.', 'Visser, C. E.', 'Sterk, P. J.', 'Lutter, R.', 'de Jong, M. D.']",BMC Infect Dis,,,True
83e137405afc87914e9128afa5aec46cc2b152cd,PMC,Seroepidemiologic Survey of Potential Pathogens in Obligate and Facultative Scavenging Avian Species in California,http://dx.doi.org/10.1371/journal.pone.0143018,PMC4659623,26606755,CC BY,"Throughout the world, populations of scavenger birds are declining rapidly with some populations already on the brink of extinction. Much of the current research into the factors contributing to these declines has focused on exposure to drug residues, lead, and other toxins. Despite increased monitoring of these declining populations, little is known about infectious diseases affecting scavenger bird species. To assess potential infectious disease risks to both obligate and facultative scavenger bird species, we performed a serosurvey for eleven potential pathogens in three species of scavenging birds in California: the California condor (Gymnogyps californianus), turkey vulture (Cathartes aura) and golden eagle (Aquila chrysaetos). California condors were seropositive for avian adenovirus, infectious bronchitis virus, Mycoplasma gallisepticum, avian paramyxovirus-2, West Nile virus (WNV) and Toxoplasma gondii. Golden eagles were seropositive for avian adenovirus, Chlamydophila psittaci and Toxoplasma gondii, and turkey vultures were seropositive for avian adenovirus, Chlamydophila psittaci, avian paramyxovirus-1, Toxoplasma gondii and WNV. Risk factor analyses indicated that rearing site and original release location were significantly associated with a positive serologic titer to WNV among free-flying condors. This study provides preliminary baseline data on infectious disease exposure in these populations for aiding in early disease detection and provides potentially critical information for conservation of the endangered California condor as it continues to expand its range and encounter new infectious disease threats.",2015 Nov 25,"['Straub, Mary H.', 'Kelly, Terra R.', 'Rideout, Bruce A.', 'Eng, Curtis', 'Wynne, Janna', 'Braun, Josephine', 'Johnson, Christine K.']",PLoS One,,,True
d85a85112817de11b60dd2e8f8177a48c3015442,PMC,Vaccines Through Centuries: Major Cornerstones of Global Health,http://dx.doi.org/10.3389/fpubh.2015.00269,PMC4659912,26636066,CC BY,"Multiple cornerstones have shaped the history of vaccines, which may contain live-attenuated viruses, inactivated organisms/viruses, inactivated toxins, or merely segments of the pathogen that could elicit an immune response. The story began with Hippocrates 400 B.C. with his description of mumps and diphtheria. No further discoveries were recorded until 1100 A.D. when the smallpox vaccine was described. During the eighteenth century, vaccines for cholera and yellow fever were reported and Edward Jenner, the father of vaccination and immunology, published his work on smallpox. The nineteenth century was a major landmark, with the “Germ Theory of disease” of Louis Pasteur, the discovery of the germ tubercle bacillus for tuberculosis by Robert Koch, and the isolation of pneumococcus organism by George Miller Sternberg. Another landmark was the discovery of diphtheria toxin by Emile Roux and its serological treatment by Emil Von Behring and Paul Ehrlih. In addition, Pasteur was able to generate the first live-attenuated viral vaccine against rabies. Typhoid vaccines were then developed, followed by the plague vaccine of Yersin. At the beginning of World War I, the tetanus toxoid was introduced, followed in 1915 by the pertussis vaccine. In 1974, The Expanded Program of Immunization was established within the WHO for bacille Calmette–Guerin, Polio, DTP, measles, yellow fever, and hepatitis B. The year 1996 witnessed the launching of the International AIDS Vaccine Initiative. In 1988, the WHO passed a resolution to eradicate polio by the year 2000 and in 2006; the first vaccine to prevent cervical cancer was developed. In 2010, “The Decade of vaccines” was launched, and on April 1st 2012, the United Nations launched the “shot@Life” campaign. In brief, the armamentarium of vaccines continues to grow with more emphasis on safety, availability, and accessibility. This mini review highlights the major historical events and pioneers in the course of development of vaccines, which have eradicated so many life-threatening diseases, despite the vaccination attitudes and waves appearing through history.",2015 Nov 26,"['Hajj Hussein, Inaya', 'Chams, Nour', 'Chams, Sana', 'El Sayegh, Skye', 'Badran, Reina', 'Raad, Mohamad', 'Gerges-Geagea, Alice', 'Leone, Angelo', 'Jurjus, Abdo']",Front Public Health,,,True
4149c3d415d6963eb002ec43810b5b4a97838465,PMC,X-ray structure and activities of an essential Mononegavirales L-protein domain,http://dx.doi.org/10.1038/ncomms9749,PMC4659945,26549102,CC BY,"The L protein of mononegaviruses harbours all catalytic activities for genome replication and transcription. It contains six conserved domains (CR-I to -VI; Fig. 1a). CR-III has been linked to polymerase and polyadenylation activity, CR-V to mRNA capping and CR-VI to cap methylation. However, how these activities are choreographed is poorly understood. Here we present the 2.2-Å X-ray structure and activities of CR-VI+, a portion of human Metapneumovirus L consisting of CR-VI and the poorly conserved region at its C terminus, the +domain. The CR-VI domain has a methyltransferase fold, which besides the typical S-adenosylmethionine-binding site ((SAM)P) also contains a novel pocket ((NS)P) that can accommodate a nucleoside. CR-VI lacks an obvious cap-binding site, and the (SAM)P-adjoining site holding the nucleotides undergoing methylation ((SUB)P) is unusually narrow because of the overhanging +domain. CR-VI+ sequentially methylates caps at their 2′O and N7 positions, and also displays nucleotide triphosphatase activity.",2015 Nov 9,"['Paesen, Guido C.', 'Collet, Axelle', 'Sallamand, Corinne', 'Debart, Françoise', 'Vasseur, Jean-Jacques', 'Canard, Bruno', 'Decroly, Etienne', 'Grimes, Jonathan M.']",Nat Commun,,,True
3801133ed6765a0ef28482c6b0d7e220340817c6,PMC,X-ray structure and activities of an essential Mononegavirales L-protein domain,http://dx.doi.org/10.1038/ncomms9749,PMC4659945,26549102,CC BY,"The L protein of mononegaviruses harbours all catalytic activities for genome replication and transcription. It contains six conserved domains (CR-I to -VI; Fig. 1a). CR-III has been linked to polymerase and polyadenylation activity, CR-V to mRNA capping and CR-VI to cap methylation. However, how these activities are choreographed is poorly understood. Here we present the 2.2-Å X-ray structure and activities of CR-VI+, a portion of human Metapneumovirus L consisting of CR-VI and the poorly conserved region at its C terminus, the +domain. The CR-VI domain has a methyltransferase fold, which besides the typical S-adenosylmethionine-binding site ((SAM)P) also contains a novel pocket ((NS)P) that can accommodate a nucleoside. CR-VI lacks an obvious cap-binding site, and the (SAM)P-adjoining site holding the nucleotides undergoing methylation ((SUB)P) is unusually narrow because of the overhanging +domain. CR-VI+ sequentially methylates caps at their 2′O and N7 positions, and also displays nucleotide triphosphatase activity.",2015 Nov 9,"['Paesen, Guido C.', 'Collet, Axelle', 'Sallamand, Corinne', 'Debart, Françoise', 'Vasseur, Jean-Jacques', 'Canard, Bruno', 'Decroly, Etienne', 'Grimes, Jonathan M.']",Nat Commun,,,False
c65fdbefc02d44dbadad79451a6253465f075837,PMC,Inferring the hosts of coronavirus using dual statistical models based on nucleotide composition,http://dx.doi.org/10.1038/srep17155,PMC4660426,26607834,CC BY,"Many coronaviruses are capable of interspecies transmission. Some of them have caused worldwide panic as emerging human pathogens in recent years, e.g., severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In order to assess their threat to humans, we explored to infer the potential hosts of coronaviruses using a dual-model approach based on nineteen parameters computed from spike genes of coronaviruses. Both the support vector machine (SVM) model and the Mahalanobis distance (MD) discriminant model achieved high accuracies in leave-one-out cross-validation of training data consisting of 730 representative coronaviruses (99.86% and 98.08% respectively). Predictions on 47 additional coronaviruses precisely conformed to conclusions or speculations by other researchers. Our approach is implemented as a web server that can be accessed at http://bioinfo.ihb.ac.cn/seq2hosts.",2015 Nov 26,"['Tang, Qin', 'Song, Yulong', 'Shi, Mijuan', 'Cheng, Yingyin', 'Zhang, Wanting', 'Xia, Xiao-Qin']",Sci Rep,,,True
6389f677ca08ac014611fe48723556b78dbd8744,PMC,Inferring the hosts of coronavirus using dual statistical models based on nucleotide composition,http://dx.doi.org/10.1038/srep17155,PMC4660426,26607834,CC BY,"Many coronaviruses are capable of interspecies transmission. Some of them have caused worldwide panic as emerging human pathogens in recent years, e.g., severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In order to assess their threat to humans, we explored to infer the potential hosts of coronaviruses using a dual-model approach based on nineteen parameters computed from spike genes of coronaviruses. Both the support vector machine (SVM) model and the Mahalanobis distance (MD) discriminant model achieved high accuracies in leave-one-out cross-validation of training data consisting of 730 representative coronaviruses (99.86% and 98.08% respectively). Predictions on 47 additional coronaviruses precisely conformed to conclusions or speculations by other researchers. Our approach is implemented as a web server that can be accessed at http://bioinfo.ihb.ac.cn/seq2hosts.",2015 Nov 26,"['Tang, Qin', 'Song, Yulong', 'Shi, Mijuan', 'Cheng, Yingyin', 'Zhang, Wanting', 'Xia, Xiao-Qin']",Sci Rep,,,False
c3b24e7070067eba2414138f7532d66ae829f9be,PMC,Viral aetiology of common colds of outpatient children at primary care level and the use of antibiotics,http://dx.doi.org/10.1590/0074-02760150154,PMC4660617,26560978,CC BY,"Although antibiotics are ineffective against viral respiratory infections, studies have shown high rates of prescriptions worldwide. We conducted a study in Brazil to determine the viral aetiologies of common colds in children and to describe the use of antibiotics for these patients. Children up to 12 years with common colds were enrolled from March 2008-February 2009 at a primary care level facility and followed by regular telephone calls and medical consultations. A nasopharyngeal wash was obtained at enrollment and studied by direct fluorescence assay and polymerase chain reaction for nine different types of virus. A sample of 134 patients was obtained, median age 2.9 years (0.1-11.2 y). Respiratory viruses were detected in 73.9% (99/134) with a coinfection rate of 30.3% (30/99). Rhinovirus was the most frequent virus (53/134; 39.6%), followed by influenza (33/134; 24.6%) and respiratory syncytial virus (8/134; 13.4%). Antibiotic prescription rate was 39.6% (53/134) and 69.8% (37/53) were considered inappropriate. Patients with influenza infection received antibiotics inappropriately in a greater proportion of cases when compared to respiratory syncytial virus and rhinovirus infections (p = 0.016). The rate of inappropriate use of antibiotics was very high and patients with influenza virus infection were prescribed antibiotics inappropriately in a greater proportion of cases.",2015 Nov,"['Kamikawa, Janete', 'Granato, Celso Francisco Hernandes', 'Bellei, Nancy']",Mem Inst Oswaldo Cruz,,,True
681a8e1fb48060f3b784fb224d80d6ed43510bda,PMC,Detection of respiratory syncytial virus and rhinovirus in healthy infants,http://dx.doi.org/10.1186/s13104-015-1695-6,PMC4660840,26608824,CC BY,"BACKGROUND: Despite the research importance of rhinovirus detection in asymptomatic healthy infants, the literature remains sparse. OBJECTIVE: To investigate the prevalence of respiratory syncytial virus (RSV) and rhinovirus (and its species). METHODS: We conducted a cross-sectional study of 110 healthy, non-hospitalized infants without acute illness at an academic medical center from November 2013 through May 2014. We tested nasal swab specimens by using polymerase chain reaction and genetic sequencing. RESULTS: Overall, the median age was 3.8 months (IQR 2.0–5.1 months), 56 % were male, and 90 % were born >37 weeks. RSV was detected in nasal swabs from infants (1.8 %). By contrast, rhinovirus was detected in nasal swabs from 16 infants (14.5 %). Molecular typing assay revealed rhinovirus species: six rhinovirus-A (5.5 %), one rhinovirus-B (0.9 %), eight rhinovirus-C (7.3 %), and one untypeable (0.9 %). CONCLUSIONS: In this cross-sectional study of healthy, community-based infants, RSV was rare (<2 %) in nasal swabs, while rhinovirus was detected in 14.5 % with a predominance of rhinovirus-A and -C. These finding are important for understanding the clinical significance of rhinovirus detection among infants hospitalized for bronchiolitis.",2015 Nov 25,"['Hasegawa, Kohei', 'Linnemann, Rachel W.', 'Avadhanula, Vasanthi', 'Mansbach, Jonathan M.', 'Piedra, Pedro A.', 'Gern, James E.', 'Camargo, Carlos A.']",BMC Res Notes,,,True
d6b52e3814a78239e5b5116dad2383b6faa327e5,PMC,Reassessing Biological Threats: Implications for Cooperative Mitigation Strategies,http://dx.doi.org/10.3389/fpubh.2015.00251,PMC4663262,26649289,CC BY,"Multiple factors ranging from globalization to ecosystem disruption are presenting the global community with evolving biological threats to local, national, and global security that reach beyond the realm of traditional bioweapon threats. As a result, mitigation strategies have adapted necessarily to the increased diversity of biological threats. In general, response and preparedness strategies have largely shifted from being primarily reactive to traditional biological weapons to more proactive in nature. In this review, we briefly explore biological threats through a wider aperture, to embrace a greater appreciation of viral pathogens, antimicrobial resistance, and agricultural pathogens, and their potential to cause civil, economic, and political devastation. In addition, we discuss current mitigation strategies codified by the Global Health Security Agenda and the One Health paradigm as well as some of the available tools to assist with their sustainable implementation.",2015 Nov 30,"['Galloway, Summer Elise', 'Petzing, Stephanie Rachel', 'Young, Catharine Grace']",Front Public Health,,,True
4f47adf53fef07c0ca76beb4b100bbdfa54b2b0b,PMC,M1 of Murine Gamma-Herpesvirus 68 Induces Endoplasmic Reticulum Chaperone Production,http://dx.doi.org/10.1038/srep17228,PMC4663489,26615759,CC BY,"Viruses rely on host chaperone network to support their infection. In particular, the endoplasmic reticulum (ER) resident chaperones play key roles in synthesizing and processing viral proteins. Influx of a large amount of foreign proteins exhausts the folding capacity in ER and triggers the unfolded protein response (UPR). A fully-executed UPR comprises signaling pathways that induce ER folding chaperones, increase protein degradation, block new protein synthesis and may eventually activate apoptosis, presenting both opportunities and threats to the virus. Here, we define a role of the MHV-68M1 gene in differential modulation of UPR pathways to enhance ER chaperone production. Ectopic expression of M1 markedly induces ER chaperone genes and expansion of ER. The M1 protein accumulates in ER during infection and this localization is indispensable for its function, suggesting M1 acts from the ER. We found that M1 protein selectively induces the chaperon-producing pathways (IRE1, ATF6) while, interestingly, sparing the translation-blocking arm (PERK). We identified, for the first time, a viral factor capable of selectively intervening the initiation of ER stress signaling to induce chaperon production. This finding provides a unique opportunity of using viral protein as a tool to define the activation mechanisms of individual UPR pathways.",2015 Nov 30,"['Feng, Jiaying', 'Gong, Danyang', 'Fu, Xudong', 'Wu, Ting-ting', 'Wang, Jane', 'Chang, Jennifer', 'Zhou, Jingting', 'Lu, Gang', 'Wang, Yibin', 'Sun, Ren']",Sci Rep,,,True
102bc38cfa807c84917545044b9738c285c196df,PMC,Survey and Visual Detection of Zaire ebolavirus in Clinical Samples Targeting the Nucleoprotein Gene in Sierra Leone,http://dx.doi.org/10.3389/fmicb.2015.01332,PMC4664619,26648918,CC BY,"Ebola virus (EBOV) can lead to severe hemorrhagic fever with a high risk of death in humans and other primates. To guide treatment and prevent spread of the viral infection, a rapid and sensitive detection method is required for clinical samples. Here, we described and evaluated a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method to detect Zaire ebolavirus using the nucleoprotein gene (NP) as a target sequence. Two different techniques were used, a calcein/Mn(2+) complex chromogenic method and real-time turbidity monitoring. The RT-LAMP assay detected the NP target sequence with a limit of 4.56 copies/μL within 45 min under 61°C, a similar even or increase in sensitivity than that of real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, all pseudoviral particles or non- Zaire EBOV genomes were negative for LAMP detection, indicating that the assay was highly specific for EBOV. To appraise the availability of the RT-LAMP method for use in clinical diagnosis of EBOV, of 417 blood or swab samples collected from patients with clinically suspected infections in Sierra Leone, 307 were identified for RT-LAMP-based surveillance of EBOV. Therefore, the highly specific and sensitive RT-LAMP method allows the rapid detection of EBOV, and is a suitable tool for clinical screening, diagnosis, and primary quarantine purposes.",2015 Dec 1,"['Li, Huan', 'Wang, Xuesong', 'Liu, Wei', 'Wei, Xiao', 'Lin, Weishi', 'Li, Erna', 'Li, Puyuan', 'Dong, Derong', 'Cui, Lifei', 'Hu, Xuan', 'Li, Boxing', 'Ma, Yanyan', 'Zhao, Xiangna', 'Liu, Chao', 'Yuan, Jing']",Front Microbiol,,,False
89686b2cea177c64849d62d6224cf976e300abd0,PMC,Survey and Visual Detection of Zaire ebolavirus in Clinical Samples Targeting the Nucleoprotein Gene in Sierra Leone,http://dx.doi.org/10.3389/fmicb.2015.01332,PMC4664619,26648918,CC BY,"Ebola virus (EBOV) can lead to severe hemorrhagic fever with a high risk of death in humans and other primates. To guide treatment and prevent spread of the viral infection, a rapid and sensitive detection method is required for clinical samples. Here, we described and evaluated a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method to detect Zaire ebolavirus using the nucleoprotein gene (NP) as a target sequence. Two different techniques were used, a calcein/Mn(2+) complex chromogenic method and real-time turbidity monitoring. The RT-LAMP assay detected the NP target sequence with a limit of 4.56 copies/μL within 45 min under 61°C, a similar even or increase in sensitivity than that of real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, all pseudoviral particles or non- Zaire EBOV genomes were negative for LAMP detection, indicating that the assay was highly specific for EBOV. To appraise the availability of the RT-LAMP method for use in clinical diagnosis of EBOV, of 417 blood or swab samples collected from patients with clinically suspected infections in Sierra Leone, 307 were identified for RT-LAMP-based surveillance of EBOV. Therefore, the highly specific and sensitive RT-LAMP method allows the rapid detection of EBOV, and is a suitable tool for clinical screening, diagnosis, and primary quarantine purposes.",2015 Dec 1,"['Li, Huan', 'Wang, Xuesong', 'Liu, Wei', 'Wei, Xiao', 'Lin, Weishi', 'Li, Erna', 'Li, Puyuan', 'Dong, Derong', 'Cui, Lifei', 'Hu, Xuan', 'Li, Boxing', 'Ma, Yanyan', 'Zhao, Xiangna', 'Liu, Chao', 'Yuan, Jing']",Front Microbiol,,,False
4ecd138ab31f520b06c5cf095657fab2685a8209,PMC,Survey and Visual Detection of Zaire ebolavirus in Clinical Samples Targeting the Nucleoprotein Gene in Sierra Leone,http://dx.doi.org/10.3389/fmicb.2015.01332,PMC4664619,26648918,CC BY,"Ebola virus (EBOV) can lead to severe hemorrhagic fever with a high risk of death in humans and other primates. To guide treatment and prevent spread of the viral infection, a rapid and sensitive detection method is required for clinical samples. Here, we described and evaluated a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method to detect Zaire ebolavirus using the nucleoprotein gene (NP) as a target sequence. Two different techniques were used, a calcein/Mn(2+) complex chromogenic method and real-time turbidity monitoring. The RT-LAMP assay detected the NP target sequence with a limit of 4.56 copies/μL within 45 min under 61°C, a similar even or increase in sensitivity than that of real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, all pseudoviral particles or non- Zaire EBOV genomes were negative for LAMP detection, indicating that the assay was highly specific for EBOV. To appraise the availability of the RT-LAMP method for use in clinical diagnosis of EBOV, of 417 blood or swab samples collected from patients with clinically suspected infections in Sierra Leone, 307 were identified for RT-LAMP-based surveillance of EBOV. Therefore, the highly specific and sensitive RT-LAMP method allows the rapid detection of EBOV, and is a suitable tool for clinical screening, diagnosis, and primary quarantine purposes.",2015 Dec 1,"['Li, Huan', 'Wang, Xuesong', 'Liu, Wei', 'Wei, Xiao', 'Lin, Weishi', 'Li, Erna', 'Li, Puyuan', 'Dong, Derong', 'Cui, Lifei', 'Hu, Xuan', 'Li, Boxing', 'Ma, Yanyan', 'Zhao, Xiangna', 'Liu, Chao', 'Yuan, Jing']",Front Microbiol,,,True
c1eb7483446895edd38acb64e683bfd905d54211,PMC,Psoralen Inactivation of Viruses: A Process for the Safe Manipulation of Viral Antigen and Nucleic Acid,http://dx.doi.org/10.3390/v7112912,PMC4664985,26569291,CC BY,"High consequence human pathogenic viruses must be handled at biosafety level 2, 3 or 4 and must be rendered non-infectious before they can be utilized for molecular or immunological applications at lower biosafety levels. Here we evaluate psoralen-inactivated Arena-, Bunya-, Corona-, Filo-, Flavi- and Orthomyxoviruses for their suitability as antigen in immunological processes and as template for reverse transcription PCR and sequencing. The method of virus inactivation using a psoralen molecule appears to have broad applicability to RNA viruses and to leave both the particle and RNA of the treated virus intact, while rendering the virus non-infectious.",2015 Nov 12,"['Schneider, Katherine', 'Wronka-Edwards, Loni', 'Leggett-Embrey, Melissa', 'Walker, Eric', 'Sun, Peifang', 'Ondov, Brian', 'Wyman, Travis H.', 'Rosovitz, MJ', 'Bohn, Sherry S.', 'Burans, James', 'Kochel, Tadeusz']",Viruses,,,True
3359ea81b72a9d6002755539aa7f91bde5fc87bb,PMC,Fluorescent Protein Approaches in Alpha Herpesvirus Research,http://dx.doi.org/10.3390/v7112915,PMC4664988,26610544,CC BY,"In the nearly two decades since the popularization of green fluorescent protein (GFP), fluorescent protein-based methodologies have revolutionized molecular and cell biology, allowing us to literally see biological processes as never before. Naturally, this revolution has extended to virology in general, and to the study of alpha herpesviruses in particular. In this review, we provide a compendium of reported fluorescent protein fusions to herpes simplex virus 1 (HSV-1) and pseudorabies virus (PRV) structural proteins, discuss the underappreciated challenges of fluorescent protein-based approaches in the context of a replicating virus, and describe general strategies and best practices for creating new fluorescent fusions. We compare fluorescent protein methods to alternative approaches, and review two instructive examples of the caveats associated with fluorescent protein fusions, including describing several improved fluorescent capsid fusions in PRV. Finally, we present our future perspectives on the types of powerful experiments these tools now offer.",2015 Nov 19,"['Hogue, Ian B.', 'Bosse, Jens B.', 'Engel, Esteban A.', 'Scherer, Julian', 'Hu, Jiun-Ruey', 'del Rio, Tony', 'Enquist, Lynn W.']",Viruses,,,True
c75ed4c49d52ac5862313eb9d22cad197df1c138,PMC,"Novel avian single-chain fragment variable (scFv) targets dietary gluten and related natural grain prolamins, toxic entities of celiac disease",http://dx.doi.org/10.1186/s12896-015-0223-z,PMC4666168,26625857,CC BY,"BACKGROUND: Celiac disease (CD) is a chronic, small intestinal inflammatory disease mediated by dietary gluten and related prolamins. The only current therapeutic option is maintenance of a strict life-long gluten-free diet, which implies substantial burden for CD patients. Different treatment regimes might be feasible, including masking of toxic celiac peptides with blocking antibodies or fragments thereof. The objective of this study was therefore to select and produce a recombinant avian single-chain fragment variable (scFv) directed against peptic-tryptic digested gliadin (PT-Gliadin) and related celiac toxic entities. RESULTS: Gluten-free raised chicken of same age were immunized with PT-Gliadin. Chicken splenic lymphocytes, selected with antigen-coated magnetic beads, served as RNA source for the generation of cDNA. Chicken V(H) and V(L) genes were amplified from the cDNA by PCR to generate full-length scFv constructs consisting of V(H) and V(L) fragments joined by a linker sequence. ScFv constructs were ligated in a prokaryotic expression vector, which provides a C-terminal hexahistidine tag. ScFvs from several bacterial clones were expressed in soluble form and crude cell lysates screened for binding to PT-Gliadin by ELISA. We identified an enriched scFv motif, which showed reactivity to PT-Gliadin. One selected scFv candidate was expressed and purified to homogeneity. Polyclonal anti-PT-Gliadin IgY, purified from egg yolk of immunized chicken, served as control. ScFv binds in a dose-dependent manner to PT-Gliadin, comparable to IgY. Furthermore, IgY competitively displaces scFv from PT-Gliadin and natural wheat flour digest, indicating a common epitope of scFv and IgY. ScFv was tested for reactivity to different gastric digested dietary grain flours. ScFv detects common and khorasan wheat comparably with binding affinities in the high nanomolar range, while rye is detected to a lesser extent. Notably, barley and cereals which are part of the gluten-free diet, like corn and rice, are not detected by scFv. Similarly, the pseudo-grain amaranth, used as gluten-free alternative, is not targeted by scFv. This data indicate that scFv specifically recognizes toxic cereal peptides relevant in CD. CONCLUSION: ScFv can be of benefit for future CD treatment regimes.",2015 Dec 1,"['Stadlmann, Valerie', 'Harant, Hanna', 'Korschineck, Irina', 'Hermann, Marcela', 'Forster, Florian', 'Missbichler, Albert']",BMC Biotechnol,,,True
1244246ac28247b5674d6f4a8587e064bb565d7f,PMC,"Live Bird Exposure among the General Public, Guangzhou, China, May 2013",http://dx.doi.org/10.1371/journal.pone.0143582,PMC4666652,26623646,CC BY,"BACKGROUND: A novel avian-origin influenza A(H7N9) caused a major outbreak in Mainland China in early 2013. Exposure to live poultry was believed to be the major route of infection. There are limited data on how the general public changes their practices regarding live poultry exposure in response to the early outbreak of this novel influenza and the frequency of population exposure to live poultry in different areas of China. METHODOLOGY: This study investigated population exposures to live birds from various sources during the outbreak of H7N9 in Guangzhou city, China in 2013 and compared them with those observed during the 2006 influenza A(H5N1) outbreak. Adults were telephone-interviewed using two-stage sampling, stratified by three residential areas of Guangzhou: urban areas and two semi-rural areas in one of which (Zengcheng) A(H7N9) virus was detected in a chicken from wet markets. Logistic regression models were built to describe practices protecting against avian influenza, weighted by age and gender, and then compare these practices across residential areas in 2013 with those from a comparable 2006 survey. PRINCIPAL FINDINGS: Of 1196 respondents, 45% visited wet markets at least daily and 22.0% reported buying live birds from wet markets at least weekly in April-May, 2013, after the H7N9 epidemic was officially declared in late March 2013. Of those buying live birds, 32.3% reported touching birds when buying and 13.7% would slaughter the poultry at home. Although only 10.1% of the respondents reported raising backyard birds, 92.1% of those who did so had physical contact with the birds they raised. Zengcheng respondents were less likely to report buying live birds from wet markets, but more likely to buy from other sources when compared to urban respondents. Compared with the 2006 survey, the prevalence of buying live birds from wet markets, touching when buying and slaughtering birds at home had substantially declined in the 2013 survey. CONCLUSION/SIGNIFICANCE: Although population exposures to live poultry were substantially fewer in 2013 compared to 2006, wet markets and backyard poultry remained the two major sources of live bird exposures for the public in Guangzhou in 2013. Zengcheng residents seemed to have reduced buying live birds from wet markets but not from other sources in response to the detection of H7N9 virus in wet markets.",2015 Dec 1,"['Liao, Qiuyan', 'Yuan, Jun', 'Lau, Eric H. Y.', 'Chen, Guang Yan', 'Yang, Zhi Cong', 'Ma, Xiao Wei', 'Chen, Jian Dong', 'Liu, Yan Hui', 'Wang, Chang', 'Tang, Xiao Ping', 'Liu, Yu Fei', 'Zhuo, Li', 'Leung, Gabriel M.', 'Zhang, Wei', 'Cowling, Benjamin J.', 'Wang, Ming', 'Fielding, Richard']",PLoS One,,,True
f6e4ddea2e155bf319fedff2b6111ba9ee863f1e,PMC,Proteomic Analysis of the Vitreous following Experimental Retinal Detachment in Rabbits,http://dx.doi.org/10.1155/2015/583040,PMC4667062,26664739,CC BY,"Purpose. The pathogenesis of rhegmatogenous retinal detachment (RRD) remains incompletely understood, with no clinically effective treatment for potentially severe complications such as photoreceptor cell death and proliferative vitreoretinopathy. Here we investigate the protein profile of the vitreous following experimental retinal detachment using a comparative proteomic based approach. Materials and Methods. Retinal detachment was created in the right eyes of six New Zealand red pigmented rabbits. Sham surgery was undertaken in five other rabbits that were used as controls. After seven days the eyes were enucleated and the vitreous was removed. The vitreous samples were evaluated with two-dimensional polyacrylamide gel electrophoresis and the differentially expressed proteins were identified with tandem mass spectrometry. Results. Ten protein spots were found to be at least twofold differentially expressed when comparing the vitreous samples of the sham and retinal detachment surgery groups. Protein spots that were upregulated in the vitreous following retinal detachment were identified as albumin fragments, and those downregulated were found to be peroxiredoxin 2, collagen-Iα1 fragment, and α-1-antiproteinase F. Conclusions. Proteomic investigation of the rabbit vitreous has identified a set of proteins that help further our understanding of the pathogenesis of rhegmatogenous retinal detachment and its complications.",2015 Nov 18,"['Mandal, Nakul', 'Lewis, Geoffrey P.', 'Fisher, Steven K.', 'Heegaard, Steffen', 'Prause, Jan U.', 'la Cour, Morten', 'Vorum, Henrik', 'Honoré, Bent']",J Ophthalmol,,,True
dc3d3e12aa6087b1141910cf58ac7f37c8cd0793,PMC,CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation,http://dx.doi.org/10.1038/srep17548,PMC4667186,26626303,CC BY,"Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.",2015 Dec 2,"['Kim, Jin Hyoung', 'Choi, Jin Young', 'Kim, Seong Bum', 'Uyangaa, Erdenebelig', 'Patil, Ajit Mahadev', 'Han, Young Woo', 'Park, Sang-Youel', 'Lee, John Hwa', 'Kim, Koanhoi', 'Eo, Seong Kug']",Sci Rep,,,True
0ef13a3b7b9def8cb24c319c24e368ace22ccb0c,PMC,CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation,http://dx.doi.org/10.1038/srep17548,PMC4667186,26626303,CC BY,"Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.",2015 Dec 2,"['Kim, Jin Hyoung', 'Choi, Jin Young', 'Kim, Seong Bum', 'Uyangaa, Erdenebelig', 'Patil, Ajit Mahadev', 'Han, Young Woo', 'Park, Sang-Youel', 'Lee, John Hwa', 'Kim, Koanhoi', 'Eo, Seong Kug']",Sci Rep,,,False
6c982280e9ca5251ee74d0f2b84489a63a68c5bb,PMC,Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity,http://dx.doi.org/10.1038/srep17577,PMC4667252,26627732,CC BY,"Influenza virus (IFV) infection is a common cause of severe viral pneumonia associated with acute respiratory distress syndrome (ARDS), which is difficult to control with general immunosuppressive therapy including corticosteroids due to the unfavorable effect on viral replication. Studies have suggested that the excessive activation of the innate immunity by IFV is responsible for severe pathologies. In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. We found that influenza pneumonia was dramatically attenuated in Card9-deficient mice, which showed improved mortality with reduced inflammatory cytokines and chemokines in the infected lungs. However, viral clearance, type-I interferon production, and the development of anti-viral B and T cell immunity were not compromised by CARD9 deficiency. Syk or CARD9-deficient DCs but not macrophages showed impaired cytokine but not type-I interferon production in response to IFV in vitro, indicating a possible role for the Syk-CARD9 pathway in DCs in excessive inflammation of IFV-infected lungs. Therefore, inhibition of this pathway is an ideal therapeutic target for severe influenza pneumonia without affecting viral clearance.",2015 Dec 2,"['Uematsu, Takayuki', 'Iizasa, Ei’ichi', 'Kobayashi, Noritada', 'Yoshida, Hiroki', 'Hara, Hiromitsu']",Sci Rep,,,True
5985c7d31f6f88ce569f9a44759a14e50fad41ac,PMC,Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity,http://dx.doi.org/10.1038/srep17577,PMC4667252,26627732,CC BY,"Influenza virus (IFV) infection is a common cause of severe viral pneumonia associated with acute respiratory distress syndrome (ARDS), which is difficult to control with general immunosuppressive therapy including corticosteroids due to the unfavorable effect on viral replication. Studies have suggested that the excessive activation of the innate immunity by IFV is responsible for severe pathologies. In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. We found that influenza pneumonia was dramatically attenuated in Card9-deficient mice, which showed improved mortality with reduced inflammatory cytokines and chemokines in the infected lungs. However, viral clearance, type-I interferon production, and the development of anti-viral B and T cell immunity were not compromised by CARD9 deficiency. Syk or CARD9-deficient DCs but not macrophages showed impaired cytokine but not type-I interferon production in response to IFV in vitro, indicating a possible role for the Syk-CARD9 pathway in DCs in excessive inflammation of IFV-infected lungs. Therefore, inhibition of this pathway is an ideal therapeutic target for severe influenza pneumonia without affecting viral clearance.",2015 Dec 2,"['Uematsu, Takayuki', 'Iizasa, Ei’ichi', 'Kobayashi, Noritada', 'Yoshida, Hiroki', 'Hara, Hiromitsu']",Sci Rep,,,False
c280d46d6fa7e2c2938a5c09bd6b092e1058a9b0,PMC,Protection against Foot-and-Mouth Disease Virus in Guinea Pigs via Oral Administration of Recombinant Lactobacillus plantarum Expressing VP1,http://dx.doi.org/10.1371/journal.pone.0143750,PMC4667879,26629822,CC BY,"Mucosal vaccination is an effective strategy for generating antigen-specific immune responses against mucosal infections of foot-and-mouth disease virus (FMDV). In this study, Lactobacillus plantarum strains NC8 and WCFS1 were used as oral delivery vehicles containing a pSIP411-VP1 recombinant plasmid to initiate mucosal and systemic immune responses in guinea pigs. Guinea pigs were orally vaccinated (three doses) with NC8-pSIP411, NC8-pSIP411-VP1, WCFS1-pSIP411, WCFS1-pSIP411-VP1 or milk. Animals immunized with NC8-pSIP411-VP1 and WCFS1-pSIP411-VP1 developed high levels of antigen-specific serum IgG, IgA, IgM, mucosal secretory IgA (sIgA) and neutralizing antibodies, and revealed stronger cell-mediated immune responses and enhanced protection against FMDV challenge compared with control groups. The recombinant pSIP411-VP1 effectively improved immunoprotection against FMDV in guinea pigs.",2015 Dec 2,"['Wang, Miao', 'Pan, Li', 'Zhou, Peng', 'Lv, Jianliang', 'Zhang, Zhongwang', 'Wang, Yonglu', 'Zhang, Yongguang']",PLoS One,,,True
8fddf78a6b3a823c0ebeb2dfbfe274e46fee97f3,PMC,Brain Meta-Transcriptomics from Harbor Seals to Infer the Role of the Microbiome and Virome in a Stranding Event,http://dx.doi.org/10.1371/journal.pone.0143944,PMC4668051,26630132,CC BY,"Marine diseases are becoming more frequent, and tools for identifying pathogens and disease reservoirs are needed to help prevent and mitigate epizootics. Meta-transcriptomics provides insights into disease etiology by cataloguing and comparing sequences from suspected pathogens. This method is a powerful approach to simultaneously evaluate both the viral and bacterial communities, but few studies have applied this technique in marine systems. In 2009 seven harbor seals, Phoca vitulina, stranded along the California coast from a similar brain disease of unknown cause of death (UCD). We evaluated the differences between the virome and microbiome of UCDs and harbor seals with known causes of death. Here we determined that UCD stranded animals had no viruses in their brain tissue. However, in the bacterial community, we identified Burkholderia and Coxiella burnetii as important pathogens associated with this stranding event. Burkholderia were 100% prevalent and ~2.8 log2 fold more abundant in the UCD animals. Further, while C. burnetii was found in only 35.7% of all samples, it was highly abundant (~94% of the total microbial community) in a single individual. In this harbor seal, C. burnetii showed high transcription rates of invading and translation genes, implicating it in the pathogenesis of this animal. Based on these data we propose that Burkholderia taxa and C. burnetii are potentially important opportunistic neurotropic pathogens in UCD stranded harbor seals.",2015 Dec 2,"['Rosales, Stephanie M.', 'Vega Thurber, Rebecca']",PLoS One,,,True
8055b4c692a2717a904b71e948926aaf953896e5,PMC,US-like isolates of porcine epidemic diarrhea virus from Japanese outbreaks between 2013 and 2014,http://dx.doi.org/10.1186/s40064-015-1552-z,PMC4668244,26693114,CC BY,"Since late 2013, outbreaks of porcine epidemic diarrhea virus (PEDV) have reemerged in Japan. In the present study, we observed a high detection rate of PEDV, with 72.5 % (148/204) of diarrhea samples (suckling, weaned, and sows) and 88.5 % (77/87) of farms experiencing acute diarrhea found to be positive for PEDV by reverse transcription PCR. Sequencing and phylogenic analyses of the partial spike gene and ORF3 of PEDV demonstrated that all prevailing Japanese PEDV isolates belonged to novel genotypes that differed from previously reported strains and the two PEDV vaccine strains currently being used in Japan. Sequence and phylogenetic analysis revealed prevailing PEDV isolates in Japan had the greatest genetic similarity to US isolates and were not vaccine-related. Unlike vaccine strains, all prevailing field PEDV isolates in Japan were found to have a number of amino acid differences in the neutralizing epitope domain, COE, which may affect antigenicity and vaccine efficacy. The present study indicates recent PEDV isolates may have been introduced into Japan from overseas and highlights the urgent requirement of novel vaccines for controlling PEDV outbreaks in Japan.",2015 Dec 2,"['Van Diep, Nguyen', 'Norimine, Junzo', 'Sueyoshi, Masuo', 'Lan, Nguyen Thi', 'Hirai, Takuya', 'Yamaguchi, Ryoji']",Springerplus,,,True
44f82307e441f32a4ddd4ea51a8f823c593e2151,PMC,Glycyrrhizic Acid Promotes M1 Macrophage Polarization in Murine Bone Marrow-Derived Macrophages Associated with the Activation of JNK and NF-κB,http://dx.doi.org/10.1155/2015/372931,PMC4668314,26664149,CC BY,"The roots and rhizomes of Glycyrrhiza species (licorice) have been widely used as natural sweeteners and herbal medicines. The aim of this study is to investigate the effect of glycyrrhizic acid (GA) from licorice on macrophage polarization. Both phenotypic and functional activities of murine bone marrow-derived macrophages (BMDMs) treated by GA were assessed. Our results showed that GA obviously increased the cell surface expression of CD80, CD86, and MHCII molecules. Meanwhile, GA upregulated the expression of CCR7 and the production of TNF-α, IL-12, IL-6, and NO (the markers of classically activated (M1) macrophages), whereas it downregulated the expression of MR, Ym1, and Arg1 (the markers of alternatively activated (M2) macrophage). The functional tests showed that GA dramatically enhanced the uptake of FITC-dextran and E. coli K88 by BMDMs and decreased the intracellular survival of E. coli K88 and S. typhimurium. Moreover, we demonstrated that JNK and NF-κB activation are required for GA-induced NO and M1-related cytokines production, while ERK1/2 pathway exhibits a regulatory effect via induction of IL-10. Together, these findings indicated that GA promoted polarization of M1 macrophages and enhanced its phagocytosis and bactericidal capacity. The results expanded our knowledge about the role of GA in macrophage polarization.",2015 Nov 19,"['Mao, Yulong', 'Wang, Baikui', 'Xu, Xin', 'Du, Wei', 'Li, Weifen', 'Wang, Youming']",Mediators Inflamm,,,True
4e6d4c7d205f8a78c8b6adf1e0a27a23254851d7,PMC,Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets,http://dx.doi.org/10.1038/srep17554,PMC4668369,26631542,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel and highly pathogenic human coronavirus and has quickly spread to other countries in the Middle East, Europe, North Africa and Asia since 2012. Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε, and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. Further analysis showed that ORF4b could also inhibit IRF3 and IRF7-induced production of IFN-β, whereas deletion of the nuclear localization signal of ORF4b abrogated its ability to inhibit IRF3 and IRF7-induced production of IFN-β, but not IFN-β production induced by RIG-I, MDA5, MAVS, IKKε, and TBK-1, suggesting that ORF4b could inhibit the induction of IFN-β in both the cytoplasm and nucleus. Collectively, these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm, and also in the nucleus with unknown mechanism. Viruses have evolved multiple strategies to evade or thwart a host’s antiviral responses. A novel human coronavirus (HCoV), Middle East respiratory syndrome coronavirus (MERS-CoV), is distinguished from other coronaviruses by its high pathogenicity and mortality. However, virulence determinants that distinguish MERS-CoV from other HCoVs have yet to be identified. MERS-CoV ORF4b antagonizes the early antiviral response, which may contribute to MERS-CoV pathogenesis. Here, we report the identification of the interferon (IFN) antagonism mechanism of MERS-CoV ORF4b. MERS-CoV ORF4b inhibits the production of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm, and also in the nucleus with unknown mechanism. These findings provide a rationale for the novel pathogenesis of MERS-CoV as well as a basis for developing a candidate therapeutic against this virus.",2015 Dec 3,"['Yang, Yang', 'Ye, Fei', 'Zhu, Na', 'Wang, Wenling', 'Deng, Yao', 'Zhao, Zhengdong', 'Tan, Wenjie']",Sci Rep,,,True
aa7340d432336723e1ffd475cd2940170b33995c,PMC,Aetiology-Specific Estimates of the Global and Regional Incidence and Mortality of Diarrhoeal Diseases Commonly Transmitted through Food,http://dx.doi.org/10.1371/journal.pone.0142927,PMC4668836,26632843,CC BY,"BACKGROUND: Diarrhoeal diseases are major contributors to the global burden of disease, particularly in children. However, comprehensive estimates of the incidence and mortality due to specific aetiologies of diarrhoeal diseases are not available. The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods. METHODS AND FINDINGS: We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. The nine diarrhoeal diseases assessed caused an estimated 1.8 billion (95% uncertainty interval [UI] 1.1–3.3 billion) cases and 599,000 (95% UI 472,000–802,000) deaths worldwide in 2010. The largest number of cases were caused by norovirus (677 million; 95% UI 468–1,153 million), enterotoxigenic Escherichia coli (ETEC) (233 million; 95% UI 154–380 million), Shigella spp. (188 million; 95% UI 94–379 million) and Giardia lamblia (179 million; 95% UI 125–263); the largest number of deaths were caused by norovirus (213,515; 95% UI 171,783–266,561), enteropathogenic E. coli (121,455; 95% UI 103,657–143,348), ETEC (73,041; 95% UI 55,474–96,984) and Shigella (64,993; 95% UI 48,966–92,357). There were marked regional differences in incidence and mortality for these nine diseases. Nearly 40% of cases and 43% of deaths caused by these nine diarrhoeal diseases occurred in children under five years of age. CONCLUSIONS: Diarrhoeal diseases caused by these nine pathogens are responsible for a large disease burden, particularly in children. These aetiology-specific burden estimates can inform efforts to reduce diarrhoeal diseases caused by these nine pathogens commonly transmitted through foods.",2015 Dec 3,"['Pires, Sara M.', 'Fischer-Walker, Christa L.', 'Lanata, Claudio F.', 'Devleesschauwer, Brecht', 'Hall, Aron J.', 'Kirk, Martyn D.', 'Duarte, Ana S. R.', 'Black, Robert E.', 'Angulo, Frederick J.']",PLoS One,,,True
97958d7950411acf70fa08f764cac6dabe0963a8,PMC,Aetiology-Specific Estimates of the Global and Regional Incidence and Mortality of Diarrhoeal Diseases Commonly Transmitted through Food,http://dx.doi.org/10.1371/journal.pone.0142927,PMC4668836,26632843,CC BY,"BACKGROUND: Diarrhoeal diseases are major contributors to the global burden of disease, particularly in children. However, comprehensive estimates of the incidence and mortality due to specific aetiologies of diarrhoeal diseases are not available. The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods. METHODS AND FINDINGS: We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. The nine diarrhoeal diseases assessed caused an estimated 1.8 billion (95% uncertainty interval [UI] 1.1–3.3 billion) cases and 599,000 (95% UI 472,000–802,000) deaths worldwide in 2010. The largest number of cases were caused by norovirus (677 million; 95% UI 468–1,153 million), enterotoxigenic Escherichia coli (ETEC) (233 million; 95% UI 154–380 million), Shigella spp. (188 million; 95% UI 94–379 million) and Giardia lamblia (179 million; 95% UI 125–263); the largest number of deaths were caused by norovirus (213,515; 95% UI 171,783–266,561), enteropathogenic E. coli (121,455; 95% UI 103,657–143,348), ETEC (73,041; 95% UI 55,474–96,984) and Shigella (64,993; 95% UI 48,966–92,357). There were marked regional differences in incidence and mortality for these nine diseases. Nearly 40% of cases and 43% of deaths caused by these nine diarrhoeal diseases occurred in children under five years of age. CONCLUSIONS: Diarrhoeal diseases caused by these nine pathogens are responsible for a large disease burden, particularly in children. These aetiology-specific burden estimates can inform efforts to reduce diarrhoeal diseases caused by these nine pathogens commonly transmitted through foods.",2015 Dec 3,"['Pires, Sara M.', 'Fischer-Walker, Christa L.', 'Lanata, Claudio F.', 'Devleesschauwer, Brecht', 'Hall, Aron J.', 'Kirk, Martyn D.', 'Duarte, Ana S. R.', 'Black, Robert E.', 'Angulo, Frederick J.']",PLoS One,,,False
cf5227d38a667f9612804971951c05e55d9bda01,PMC,Identification of Peptide Inhibitors of Enveloped Viruses Using Support Vector Machine,http://dx.doi.org/10.1371/journal.pone.0144171,PMC4670226,26636321,CC BY,"The peptides derived from envelope proteins have been shown to inhibit the protein-protein interactions in the virus membrane fusion process and thus have a great potential to be developed into effective antiviral therapies. There are three types of envelope proteins each exhibiting distinct structure folds. Although the exact fusion mechanism remains elusive, it was suggested that the three classes of viral fusion proteins share a similar mechanism of membrane fusion. The common mechanism of action makes it possible to correlate the properties of self-derived peptide inhibitors with their activities. Here we developed a support vector machine model using sequence-based statistical scores of self-derived peptide inhibitors as input features to correlate with their activities. The model displayed 92% prediction accuracy with the Matthew’s correlation coefficient of 0.84, obviously superior to those using physicochemical properties and amino acid decomposition as input. The predictive support vector machine model for self- derived peptides of envelope proteins would be useful in development of antiviral peptide inhibitors targeting the virus fusion process.",2015 Dec 4,"['Xu, Yongtao', 'Yu, Shui', 'Zou, Jian-Wei', 'Hu, Guixiang', 'Rahman, Noorsaadah A. B. D.', 'Othman, Rozana Binti', 'Tao, Xia', 'Huang, Meilan']",PLoS One,,,True
2a6a9de82dc0494f32530e1ee8ee7509367a04fd,PMC,Building International Genomics Collaboration for Global Health Security,http://dx.doi.org/10.3389/fpubh.2015.00264,PMC4670856,26697418,CC BY,"Genome science and technologies are transforming life sciences globally in many ways and becoming a highly desirable area for international collaboration to strengthen global health. The Genome Science Program at the Los Alamos National Laboratory is leveraging a long history of expertise in genomics research to assist multiple partner nations in advancing their genomics and bioinformatics capabilities. The capability development objectives focus on providing a molecular genomics-based scientific approach for pathogen detection, characterization, and biosurveillance applications. The general approaches include introduction of basic principles in genomics technologies, training on laboratory methodologies and bioinformatic analysis of resulting data, procurement, and installation of next-generation sequencing instruments, establishing bioinformatics software capabilities, and exploring collaborative applications of the genomics capabilities in public health. Genome centers have been established with public health and research institutions in the Republic of Georgia, Kingdom of Jordan, Uganda, and Gabon; broader collaborations in genomics applications have also been developed with research institutions in many other countries.",2015 Dec 7,"['Cui, Helen H.', 'Erkkila, Tracy', 'Chain, Patrick S. G.', 'Vuyisich, Momchilo']",Front Public Health,,,True
a138ff680ae9e158019717356e8fcab523e7cad2,PMC,Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0144475,PMC4671582,26641892,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) with pandemic potential is a major worldwide threat to public health. However, vaccine development for this pathogen lags behind as immunity associated with protection is currently largely unknown. In this study, an immunoinformatics-driven genome-wide screening strategy of vaccine targets was performed to thoroughly screen the vital and effective dominant immunogens against MERS-CoV. Conservancy and population coverage analysis of the epitopes were done by the Immune Epitope Database. The results showed that the nucleocapsid (N) protein of MERS-CoV might be a better protective immunogen with high conservancy and potential eliciting both neutralizing antibodies and T-cell responses compared with spike (S) protein. Further, the B-cell, helper T-cell and cytotoxic T lymphocyte (CTL) epitopes were screened and mapped to the N protein. A total of 15 linear and 10 conformal B-cell epitopes that may induce protective neutralizing antibodies were obtained. Additionally, a total of 71 peptides with 9-mer core sequence were identified as helper T-cell epitopes, and 34 peptides were identified as CTL epitopes. Based on the maximum HLA binding alleles, top 10 helper T-cell epitopes and CTL epitopes that may elicit protective cellular immune responses against MERS-CoV were selected as MERS vaccine candidates. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover the vast majority of the population in 15 geographic regions considered where vaccine would be employed. The B- and T-cell stimulation potentials of the screened epitopes is to be further validated for their efficient use as vaccines against MERS-CoV. Collectively, this study provides novel vaccine target candidates and may prompt further development of vaccines against MERS-CoV and other emerging infectious diseases.",2015 Dec 7,"['Shi, Jiandong', 'Zhang, Jing', 'Li, Sijin', 'Sun, Jing', 'Teng, Yumei', 'Wu, Meini', 'Li, Jianfan', 'Li, Yanhan', 'Hu, Ningzhu', 'Wang, Haixuan', 'Hu, Yunzhang']",PLoS One,,,True
06d3c7caaf09a3ae5204d955b0036aca10c6634a,PMC,Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0144475,PMC4671582,26641892,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) with pandemic potential is a major worldwide threat to public health. However, vaccine development for this pathogen lags behind as immunity associated with protection is currently largely unknown. In this study, an immunoinformatics-driven genome-wide screening strategy of vaccine targets was performed to thoroughly screen the vital and effective dominant immunogens against MERS-CoV. Conservancy and population coverage analysis of the epitopes were done by the Immune Epitope Database. The results showed that the nucleocapsid (N) protein of MERS-CoV might be a better protective immunogen with high conservancy and potential eliciting both neutralizing antibodies and T-cell responses compared with spike (S) protein. Further, the B-cell, helper T-cell and cytotoxic T lymphocyte (CTL) epitopes were screened and mapped to the N protein. A total of 15 linear and 10 conformal B-cell epitopes that may induce protective neutralizing antibodies were obtained. Additionally, a total of 71 peptides with 9-mer core sequence were identified as helper T-cell epitopes, and 34 peptides were identified as CTL epitopes. Based on the maximum HLA binding alleles, top 10 helper T-cell epitopes and CTL epitopes that may elicit protective cellular immune responses against MERS-CoV were selected as MERS vaccine candidates. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover the vast majority of the population in 15 geographic regions considered where vaccine would be employed. The B- and T-cell stimulation potentials of the screened epitopes is to be further validated for their efficient use as vaccines against MERS-CoV. Collectively, this study provides novel vaccine target candidates and may prompt further development of vaccines against MERS-CoV and other emerging infectious diseases.",2015 Dec 7,"['Shi, Jiandong', 'Zhang, Jing', 'Li, Sijin', 'Sun, Jing', 'Teng, Yumei', 'Wu, Meini', 'Li, Jianfan', 'Li, Yanhan', 'Hu, Ningzhu', 'Wang, Haixuan', 'Hu, Yunzhang']",PLoS One,,,False
fff6f848d352c486049ec8046bc44e900fefb2e3,PMC,Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0144475,PMC4671582,26641892,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) with pandemic potential is a major worldwide threat to public health. However, vaccine development for this pathogen lags behind as immunity associated with protection is currently largely unknown. In this study, an immunoinformatics-driven genome-wide screening strategy of vaccine targets was performed to thoroughly screen the vital and effective dominant immunogens against MERS-CoV. Conservancy and population coverage analysis of the epitopes were done by the Immune Epitope Database. The results showed that the nucleocapsid (N) protein of MERS-CoV might be a better protective immunogen with high conservancy and potential eliciting both neutralizing antibodies and T-cell responses compared with spike (S) protein. Further, the B-cell, helper T-cell and cytotoxic T lymphocyte (CTL) epitopes were screened and mapped to the N protein. A total of 15 linear and 10 conformal B-cell epitopes that may induce protective neutralizing antibodies were obtained. Additionally, a total of 71 peptides with 9-mer core sequence were identified as helper T-cell epitopes, and 34 peptides were identified as CTL epitopes. Based on the maximum HLA binding alleles, top 10 helper T-cell epitopes and CTL epitopes that may elicit protective cellular immune responses against MERS-CoV were selected as MERS vaccine candidates. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover the vast majority of the population in 15 geographic regions considered where vaccine would be employed. The B- and T-cell stimulation potentials of the screened epitopes is to be further validated for their efficient use as vaccines against MERS-CoV. Collectively, this study provides novel vaccine target candidates and may prompt further development of vaccines against MERS-CoV and other emerging infectious diseases.",2015 Dec 7,"['Shi, Jiandong', 'Zhang, Jing', 'Li, Sijin', 'Sun, Jing', 'Teng, Yumei', 'Wu, Meini', 'Li, Jianfan', 'Li, Yanhan', 'Hu, Ningzhu', 'Wang, Haixuan', 'Hu, Yunzhang']",PLoS One,,,False
7c31dec4fa9159b171d8e08d603ad0535a379d39,PMC,Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0144475,PMC4671582,26641892,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) with pandemic potential is a major worldwide threat to public health. However, vaccine development for this pathogen lags behind as immunity associated with protection is currently largely unknown. In this study, an immunoinformatics-driven genome-wide screening strategy of vaccine targets was performed to thoroughly screen the vital and effective dominant immunogens against MERS-CoV. Conservancy and population coverage analysis of the epitopes were done by the Immune Epitope Database. The results showed that the nucleocapsid (N) protein of MERS-CoV might be a better protective immunogen with high conservancy and potential eliciting both neutralizing antibodies and T-cell responses compared with spike (S) protein. Further, the B-cell, helper T-cell and cytotoxic T lymphocyte (CTL) epitopes were screened and mapped to the N protein. A total of 15 linear and 10 conformal B-cell epitopes that may induce protective neutralizing antibodies were obtained. Additionally, a total of 71 peptides with 9-mer core sequence were identified as helper T-cell epitopes, and 34 peptides were identified as CTL epitopes. Based on the maximum HLA binding alleles, top 10 helper T-cell epitopes and CTL epitopes that may elicit protective cellular immune responses against MERS-CoV were selected as MERS vaccine candidates. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover the vast majority of the population in 15 geographic regions considered where vaccine would be employed. The B- and T-cell stimulation potentials of the screened epitopes is to be further validated for their efficient use as vaccines against MERS-CoV. Collectively, this study provides novel vaccine target candidates and may prompt further development of vaccines against MERS-CoV and other emerging infectious diseases.",2015 Dec 7,"['Shi, Jiandong', 'Zhang, Jing', 'Li, Sijin', 'Sun, Jing', 'Teng, Yumei', 'Wu, Meini', 'Li, Jianfan', 'Li, Yanhan', 'Hu, Ningzhu', 'Wang, Haixuan', 'Hu, Yunzhang']",PLoS One,,,False
cd9b28a218d57ae7506637d96b2a396dca870e0f,PMC,"The Burden of Influenza-Associated Hospitalizations in Oman, January 2008-June 2013",http://dx.doi.org/10.1371/journal.pone.0144186,PMC4671710,26642055,CC0,"INTRODUCTION: Acute respiratory infections (ARI), including influenza, comprise a leading cause of morbidity and mortality worldwide. Influenza surveillance provides important information to inform policy on influenza control and vaccination. While the epidemiology of influenza has been well characterized in western countries, few data exist on influenza epidemiology in the Eastern Mediterranean Region. We describe the epidemiology of influenza virus in Oman. METHODS: Using syndromic case definitions and protocols, patients from four regional hospitals in Oman were enrolled in a descriptive prospective study to characterize the burden of severe acute respiratory infections (SARI) and influenza. Eligible patients provided demographic information as well as oropharyngeal (OP) and nasopharyngeal (NP) swabs. Specimens were tested for influenza A and influenza B; influenza A viruses were subtyped using RT-PCR. RESULTS: From January 2008 through June 2013, a total of 5,147 cases were enrolled and tested for influenza. Influenza strains were detected in 8% of cases for whom samples were available. Annual incidence rates ranged from 0.5 to 15.4 cases of influenza-associated SARI per 100,000 population. The median age of influenza patients was 6 years with children 0–2 years accounting for 34% of all influenza-associated hospitalizations. By contrast, the median age of non-influenza SARI cases was 1 year with children 0–2 years comprising 59% of SARI. Compared to non-influenza SARI cases, a greater proportion of influenza cases had pre-existing chronic conditions and underwent ventilation during hospitalization. CONCLUSIONS: Influenza virus is associated with a substantial proportion of SARI in Oman. Influenza in Oman approximately follows northern hemisphere seasonality, with major peaks in October to December and a lesser peak around April. The burden of influenza was greatest in children and the elderly. Future efforts should examine the burden of influenza in other potential risk groups such as pregnant women to inform interventions including targeted vaccination.",2015 Dec 7,"['Al-Awaidy, Salah', 'Hamid, Sarah', 'Al Obaidani, Idris', 'Al Baqlani, Said', 'Al Busaidi, Suleiman', 'Bawikar, Shyam', 'El-Shoubary, Waleed', 'Dueger, Erica L.', 'Said, Mayar M.', 'Elamin, Emdeldin', 'Shah, Parag', 'Talaat, Maha']",PLoS One,,,True
ff9d9713206da30022af4f9095058368eeb1f3f8,PMC,"A New Decade of Veterinary Research: Societal Relevance, Global Collaboration, and Translational Medicine",http://dx.doi.org/10.3389/fvets.2015.00001,PMC4672166,26664930,CC BY,,2015 Feb 26,"Christopher, Mary M.",Front Vet Sci,,,True
ac9e71b8ce45ac71f25abec56e4d60db6b68d703,PMC,Salmonella enterica Serovars Enteritidis Infection Alters the Indigenous Microbiota Diversity in Young Layer Chicks,http://dx.doi.org/10.3389/fvets.2015.00061,PMC4672283,26664988,CC BY,"Avian gastrointestinal (GI) tracts are highly populated with a diverse array of microorganisms that share a symbiotic relationship with their hosts and contribute to the overall health and disease state of the intestinal tract. The microbiome of the young chick is easily prone to alteration in its composition by both exogenous and endogenous factors, especially during the early posthatch period. The genetic background of the host and exposure to pathogens can impact the diversity of the microbial profile that consequently contributes to the disease progression in the host. The objective of this study was to profile the composition and structure of the gut microbiota in young chickens from two genetically distinct highly inbred lines. Furthermore, the effect of the Salmonella Enteritidis infection on altering the composition makeup of the chicken microbiome was evaluated through the 16S rRNA gene sequencing analysis. One-day-old layer chicks were challenged with S. Enteritidis and the host cecal microbiota profile as well as the degree of susceptibility to Salmonella infection was examined at 2 and 7 days post infection. Our result indicated that host genotype had a limited effect on resistance to S. Enteritidis infection. Alpha diversity, beta diversity, and overall microbiota composition were analyzed for four factors: host genotype, age, treatment, and postinfection time points. S. Enteritidis infection in young chicks was found to significantly reduce the overall diversity of the microbiota population with expansion of Enterobacteriaceae family. These changes indicated that Salmonella colonization in the GI tract of the chickens has a direct effect on altering the natural development of the GI microbiota. The impact of S. Enteritidis infection on microbial communities was also more substantial in the late stage of infection. Significant inverse correlation between Enterobacteriaceae and Lachnospiraceae family in both non-infected and infected groups, suggested possible antagonistic interaction between members of these two taxa, which could potentially influences the overall microbial population in the gut. Our results also revealed that genetic difference between two lines had minimal effect on the establishment of microbiota population. Overall, this study provided preliminary insights into the contributing role of S. Enteritidis in influencing the overall makeup of chicken’s gut microbiota.",2015 Nov 23,"['Mon, Khin K. Z.', 'Saelao, Perot', 'Halstead, Michelle M.', 'Chanthavixay, Ganrea', 'Chang, Huai-Chen', 'Garas, Lydia', 'Maga, Elizabeth A.', 'Zhou, Huaijun']",Front Vet Sci,,,True
dcceda0265e3540a12eef54836297a20d890c4a8,PMC,Detection of airborne viruses using electro-aerodynamic deposition and a field-effect transistor,http://dx.doi.org/10.1038/srep17462,PMC4672335,26642822,CC BY,"We report a technique for the detection of aerosolized viruses. Conventional field-effect-transistor (FET)-based techniques use solution-based processes, thus require antibody binding to the detection region of the FET prior to the supply of the analyte. With the method described here, virus–antibody-bound particles are delivered to the FET during detection; therefore, neither a pre-treatment antibody binding step on the FET channel nor washing process for virus–antibody-binding are necessary. Our method is based on the concept that virus–antibody-bound particles are larger than the virus or antibody alone, and thus have larger charge numbers following aerosol charging. When these particles are charged by negative ions and electro-aerodynamically deposited on a substrate, there exists a location on the substrate where neither lone virus nor antibody particles land, and where only virus–antibody-bound particles are deposited. If this location coincides with the channel of the FET, the resulting variation in the current can be used to indicate the existence of a virus. By aerosolizing a mixed solution of the virus and the antibody, only the virus–antibody-bound particles were transported to the swCNT-FET, and the electric current in the swCNT-FET decreased to 30% of that measured with no deposited particles.",2015 Dec 8,"['Park, Kyu-Tae', 'Cho, Dong-Guk', 'Park, Ji-Woon', 'Hong, Seunghun', 'Hwang, Jungho']",Sci Rep,,,True
6372aae30124dd3aca4a113413b4fc1ecc19c22c,PMC,Detection of airborne viruses using electro-aerodynamic deposition and a field-effect transistor,http://dx.doi.org/10.1038/srep17462,PMC4672335,26642822,CC BY,"We report a technique for the detection of aerosolized viruses. Conventional field-effect-transistor (FET)-based techniques use solution-based processes, thus require antibody binding to the detection region of the FET prior to the supply of the analyte. With the method described here, virus–antibody-bound particles are delivered to the FET during detection; therefore, neither a pre-treatment antibody binding step on the FET channel nor washing process for virus–antibody-binding are necessary. Our method is based on the concept that virus–antibody-bound particles are larger than the virus or antibody alone, and thus have larger charge numbers following aerosol charging. When these particles are charged by negative ions and electro-aerodynamically deposited on a substrate, there exists a location on the substrate where neither lone virus nor antibody particles land, and where only virus–antibody-bound particles are deposited. If this location coincides with the channel of the FET, the resulting variation in the current can be used to indicate the existence of a virus. By aerosolizing a mixed solution of the virus and the antibody, only the virus–antibody-bound particles were transported to the swCNT-FET, and the electric current in the swCNT-FET decreased to 30% of that measured with no deposited particles.",2015 Dec 8,"['Park, Kyu-Tae', 'Cho, Dong-Guk', 'Park, Ji-Woon', 'Hong, Seunghun', 'Hwang, Jungho']",Sci Rep,,,False
c3461b2484a2c1b0532e47afba87d235e350b9e7,PMC,De novo transcriptome reconstruction and annotation of the Egyptian rousette bat,http://dx.doi.org/10.1186/s12864-015-2124-x,PMC4672546,26643810,CC BY,"BACKGROUND: The Egyptian Rousette bat (Rousettus aegyptiacus), a common fruit bat species found throughout Africa and the Middle East, was recently identified as a natural reservoir host of Marburg virus. With Ebola virus, Marburg virus is a member of the family Filoviridae that causes severe hemorrhagic fever disease in humans and nonhuman primates, but results in little to no pathological consequences in bats. Understanding host-pathogen interactions within reservoir host species and how it differs from hosts that experience severe disease is an important aspect of evaluating viral pathogenesis and developing novel therapeutics and methods of prevention. RESULTS: Progress in studying bat reservoir host responses to virus infection is hampered by the lack of host-specific reagents required for immunological studies. In order to establish a basis for the design of reagents, we sequenced, assembled, and annotated the R. aegyptiacus transcriptome. We performed de novo transcriptome assembly using deep RNA sequencing data from 11 distinct tissues from one male and one female bat. We observed high similarity between this transcriptome and those available from other bat species. Gene expression analysis demonstrated clustering of expression profiles by tissue, where we also identified enrichment of tissue-specific gene ontology terms. In addition, we identified and experimentally validated the expression of novel coding transcripts that may be specific to this species. CONCLUSION: We comprehensively characterized the R. aegyptiacus transcriptome de novo. This transcriptome will be an important resource for understanding bat immunology, physiology, disease pathogenesis, and virus transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2124-x) contains supplementary material, which is available to authorized users.",2015 Dec 7,"['Lee, Albert K.', 'Kulcsar, Kirsten A.', 'Elliott, Oliver', 'Khiabanian, Hossein', 'Nagle, Elyse R.', 'Jones, Megan E.B.', 'Amman, Brian R.', 'Sanchez-Lockhart, Mariano', 'Towner, Jonathan S.', 'Palacios, Gustavo', 'Rabadan, Raul']",BMC Genomics,,,True
9a98d242545d1ff31799bc6197ac31e3f2cd4447,PMC,Transcriptome-Wide Cleavage Site Mapping on Cellular mRNAs Reveals Features Underlying Sequence-Specific Cleavage by the Viral Ribonuclease SOX,http://dx.doi.org/10.1371/journal.ppat.1005305,PMC4672902,26646420,CC BY,"Many viruses express factors that reduce host gene expression through widespread degradation of cellular mRNA. An example of this class of proteins is the mRNA-targeting endoribonuclease SOX from the gamma-herpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV). Previous studies indicated that cleavage of messenger RNAs (mRNA) by SOX occurs at specific locations defined by the sequence of the target RNA, which is at odds with the down-regulation of a large portion of cellular transcripts. In this study, we address this paradox by using high-throughput sequencing of cleavage intermediates combined with a custom bioinformatics-based analysis pipeline to identify SOX cleavage sites across the mRNA transcriptome. These data, coupled with targeted mutagenesis, reveal that while cleavage sites are specific and reproducible, they are defined by a degenerate sequence motif containing a small number of conserved residues rather than a strong consensus sequence. This degenerate element is well represented in both human and KSHV mRNA, and its presence correlates with RNA destabilization by SOX. This represents a new endonuclease targeting strategy, in which use of a degenerate targeting element enables RNA cleavage at specific locations without restricting the range of targets. Furthermore, it shows that strong target selectivity can be achieved without a high degree of sequence specificity.",2015 Dec 8,"['Gaglia, Marta Maria', 'Rycroft, Chris H.', 'Glaunsinger, Britt A.']",PLoS Pathog,,,True
fcb1c4ac23381ffb7dbeaad05aa5307cf4386912,PMC,Efficient Structure Resonance Energy Transfer from Microwaves to Confined Acoustic Vibrations in Viruses,http://dx.doi.org/10.1038/srep18030,PMC4673452,26647655,CC BY,"Virus is known to resonate in the confined-acoustic dipolar mode with microwave of the same frequency. However this effect was not considered in previous virus-microwave interaction studies and microwave-based virus epidemic prevention. Here we show that this structure-resonant energy transfer effect from microwaves to virus can be efficient enough so that airborne virus was inactivated with reasonable microwave power density safe for the open public. We demonstrate this effect by measuring the residual viral infectivity of influenza A virus after illuminating microwaves with different frequencies and powers. We also established a theoretical model to estimate the microwaves power threshold for virus inactivation and good agreement with experiments was obtained. Such structure-resonant energy transfer induced inactivation is mainly through physically fracturing the virus structure, which was confirmed by real-time reverse transcription polymerase chain reaction. These results provide a pathway toward establishing a new epidemic prevention strategy in open public for airborne virus.",2015 Dec 9,"['Yang, Szu-Chi', 'Lin, Huan-Chun', 'Liu, Tzu-Ming', 'Lu, Jen-Tang', 'Hung, Wan-Ting', 'Huang, Yu-Ru', 'Tsai, Yi-Chun', 'Kao, Chuan-Liang', 'Chen, Shih-Yuan', 'Sun, Chi-Kuang']",Sci Rep,,,True
6a2f8a34d948eade9535a207c36e6220f2ee1661,PMC,Efficient Structure Resonance Energy Transfer from Microwaves to Confined Acoustic Vibrations in Viruses,http://dx.doi.org/10.1038/srep18030,PMC4673452,26647655,CC BY,"Virus is known to resonate in the confined-acoustic dipolar mode with microwave of the same frequency. However this effect was not considered in previous virus-microwave interaction studies and microwave-based virus epidemic prevention. Here we show that this structure-resonant energy transfer effect from microwaves to virus can be efficient enough so that airborne virus was inactivated with reasonable microwave power density safe for the open public. We demonstrate this effect by measuring the residual viral infectivity of influenza A virus after illuminating microwaves with different frequencies and powers. We also established a theoretical model to estimate the microwaves power threshold for virus inactivation and good agreement with experiments was obtained. Such structure-resonant energy transfer induced inactivation is mainly through physically fracturing the virus structure, which was confirmed by real-time reverse transcription polymerase chain reaction. These results provide a pathway toward establishing a new epidemic prevention strategy in open public for airborne virus.",2015 Dec 9,"['Yang, Szu-Chi', 'Lin, Huan-Chun', 'Liu, Tzu-Ming', 'Lu, Jen-Tang', 'Hung, Wan-Ting', 'Huang, Yu-Ru', 'Tsai, Yi-Chun', 'Kao, Chuan-Liang', 'Chen, Shih-Yuan', 'Sun, Chi-Kuang']",Sci Rep,,,False
0cafb384b401aeefaa3286bb0cf76309434e2288,PMC,Tackling dengue fever: Current status and challenges,http://dx.doi.org/10.1186/s12985-015-0444-8,PMC4673751,26645066,CC BY,"According to recent statistics, 96 million apparent dengue infections were estimated worldwide in 2010. This figure is by far greater than the WHO prediction which indicates the rapid spread of this disease posing a growing threat to the economy and a major challenge to clinicians and health care services across the globe particularly in the affected areas. This article aims at bringing to light the current epidemiological and clinical status of the dengue fever. The relationship between genetic mutations, single nucleotide polymorphism (SNP) and the pathophysiology of disease progression will be put into perspective. It will also highlight the recent advances in dengue vaccine development. Thus far, a significant progress has been made in unraveling the risk factors and understanding the molecular pathogenesis associated with the disease. However, further insights in molecular features of the disease and the development of animal models will enormously help improving the therapeutic interventions and potentially contribute to finding new preventive measures for population at risk.",2015 Dec 9,"['Nedjadi, Taoufik', 'El-Kafrawy, Sherif', 'Sohrab, Sayed S.', 'Desprès, Philippe', 'Damanhouri, Ghazi', 'Azhar, Esam']",Virol J,,,True
3c3068bf6e652c02d85923d2438ad4c84d53071a,PMC,Social Consequences of Ebola Containment Measures in Liberia,http://dx.doi.org/10.1371/journal.pone.0143036,PMC4674104,26650630,CC BY,"INTRODUCTION: In the Ebola Virus Disease (EVD) outbreak in Liberia, two major emergency disease-control measures were cremation of bodies and enforcement of quarantine for asymptomatic individuals suspected of being in contact with a positive case. Enforced by State-related actors, these were promoted as the only method to curtail transmissions as soon as possible. However, as with other harsh measures witnessed by Liberian citizens, in many cases those measures elicited uncontrolled negative reactions within the communities (stigma; fear) that produced, in some cases, the opposite effect of that intended. METHODOLOGY: The research has been conducted in two phases, for a total of 8 weeks. Ethnography of local practices was carried out in 7 neighbourhoods in Monrovia and 5 villages in Grand Cape Mount County in Liberia. 45 Focus Group Discussions (432 participants) and 30 semi-structured interviews sustained the observing participation. Randomly selected people from different social layers were targeted. The principal investigator worked with the help of two local assistants. Perceptions and practices were both analysed. RESULTS: Participants stressed how cremation perpetuated the social breakdown that started with the isolation for the sickness. Socio-economical divides were created by inequitable management of the dead: those who could bribe the burial teams obtained a burial in a private cemetery or the use of Funeral Homes. Conversely, those in economic disadvantage were forced to send their dead for cremation. State-enforced quarantine, with a mandatory prohibition of movement, raised condemnation, strengthened stigmatization and created serious socio-economic distress. Food was distributed intermittently and some houses shared latrines with non-quarantined neighbours. Escapes were also recorded. Study participants narrated how they adopted local measures of containment, through local task forces and socially-rooted control of outsiders. They also stressed how information that was not spread built up rumours and suspicion. CONCLUSIONS: Populations experiencing an epidemic feel a high degree of social insecurity, in addition to the health hazards. Vertical and coercive measures increase mistrust and fear, producing a counter-productive effect in the containment of the epidemic. On the other hand, local communities show a will to be engaged and a high degree of flexibility in participating to the epidemic response. Efforts in the direction of awareness and community involvement could prove to be better strategy to control the epidemic and root the response on social participation.",2015 Dec 9,"['Pellecchia, Umberto', 'Crestani, Rosa', 'Decroo, Tom', 'Van den Bergh, Rafael', 'Al-Kourdi, Yasmine']",PLoS One,,,True
d1963d550043eb5a1d7c49a21530848025ac4eb2,PMC,CD8(+) T-Cells as Immune Regulators of Multiple Sclerosis,http://dx.doi.org/10.3389/fimmu.2015.00619,PMC4674574,26697014,CC BY,"The vast majority of studies regarding the immune basis of MS (and its animal model, EAE) have largely focused on CD4(+) T-cells as mediators and regulators of disease. Interestingly, CD8(+) T-cells represent the predominant T-cell population in human MS lesions and are oligoclonally expanded at the site of pathology. However, their role in the autoimmune pathologic process has been both understudied and controversial. Several animal models and MS patient studies support a pathogenic role for CNS-specific CD8(+) T-cells, whereas we and others have demonstrated a regulatory role for these cells in disease. In this review, we describe studies that have investigated the role of CD8(+) T-cells in MS and EAE, presenting evidence for both pathogenic and regulatory functions. In our studies, we have shown that cytotoxic/suppressor CD8(+) T-cells are CNS antigen-specific, MHC class I-restricted, IFNγ- and perforin-dependent, and are able to inhibit disease. The clinical relevance for CD8(+) T-cell suppressive function is best described by a lack of their function during MS relapse, and importantly, restoration of their suppressive function during quiescence. Furthermore, CD8(+) T-cells with immunosuppressive functions can be therapeutically induced in MS patients by glatiramer acetate (GA) treatment. Unlike CNS-specific CD8(+) T-cells, these immunosuppressive GA-induced CD8(+) T-cells appear to be HLA-E restricted. These studies have provided greater fundamental insight into the role of autoreactive as well as therapeutically induced CD8(+) T-cells in disease amelioration. The clinical implications for these findings are immense and we propose that this natural process can be harnessed toward the development of an effective immunotherapeutic strategy.",2015 Dec 10,"['Sinha, Sushmita', 'Boyden, Alexander W.', 'Itani, Farah R.', 'Crawford, Michael P.', 'Karandikar, Nitin J.']",Front Immunol,,,True
805dabb68b67c8ccf18480c096ffbff3fb90a745,PMC,The baseline characteristics and interim analyses of the high-risk sentinel cohort of the Vietnam Initiative on Zoonotic InfectiONS (VIZIONS),http://dx.doi.org/10.1038/srep17965,PMC4674710,26659094,CC BY,"The Vietnam Initiative for Zoonotic Infections (VIZIONS) includes community-based ‘high-risk sentinel cohort’ (HRSC) studies investigating individuals at risk of zoonotic infection due to occupational or residential exposure to animals. A total of 852 HRSC members were recruited between March 2013 and August 2014 from three provinces (Ha Noi, Dak Lak, and Dong Thap). The most numerous group (72.8%) corresponded to individuals living on farms, followed by slaughterers (16.3%) and animal health workers (8.5%). Nasal/pharyngeal and rectal swabs were collected from HRSC members at recruitment and after notifying illness. Exposure to exotic animals (including wild pigs, porcupine, monkey, civet, bamboo rat and bat) was highest for the Dak Lak cohort (53.7%), followed by Ha Noi (13.7%) and Dong Thap (4.0%). A total of 26.8% of individuals reported consumption of raw blood over the previous year; 33.6% slaughterers reported no use of protective equipment at work. Over 686 person-years of observation, 213 episodes of suspect infectious disease were notified, equivalent of 0.35 reports per person-year. Responsive samples were collected from animals in the farm cohort. There was noticeable time and space clustering of disease episodes suggesting that the VIZIONS set up is also suitable for the formal epidemiological investigation of disease outbreaks.",2015 Dec 10,"['Carrique-Mas, Juan J.', 'Tue, Ngo T.', 'Bryant, Juliet E.', 'Saylors, Karen', 'Cuong, Nguyen V.', 'Hoa, Ngo T.', 'An, Nguyen N.', 'Hien, Vo B.', 'Lao, Pham V.', 'Tu, Nguyen C.', 'Chuyen, Nguyen K.', 'Chuc, Nguyen T.K.', 'Tan, Dinh V.', 'Duong, Hoang Van V.', 'Toan, Tran K.', 'Chi, Nguyen T.Y.', 'Campbell, James', 'Rabaa, Maia A.', 'Nadjm, Behzad', 'Woolhouse, Mark', 'Wertheim, Heiman', 'Thwaites, Guy', 'Baker, Stephen']",Sci Rep,,,True
2e0fdaf23e6de0d6787519f671bc198d47f3acb1,PMC,ORBiT: Oak Ridge biosurveillance toolkit for public health dynamics,http://dx.doi.org/10.1186/1471-2105-16-S17-S4,PMC4674898,26679008,CC BY,"BACKGROUND: The digitization of health-related information through electronic health records (EHR) and electronic healthcare reimbursement claims and the continued growth of self-reported health information through social media provides both tremendous opportunities and challenges in developing effective biosurveillance tools. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build systems that can track, monitor and report such events in a timely manner. Further, it is also important to identify susceptible geographic regions and populations where emerging diseases may have a significant impact. METHODS: In this paper, we present an overview of Oak Ridge Biosurveillance Toolkit (ORBiT), which we have developed specifically to address data analytic challenges in the realm of public health surveillance. In particular, ORBiT provides an extensible environment to pull together diverse, large-scale datasets and analyze them to identify spatial and temporal patterns for various biosurveillance-related tasks. RESULTS: We demonstrate the utility of ORBiT in automatically extracting a small number of spatial and temporal patterns during the 2009-2010 pandemic H1N1 flu season using claims data. These patterns provide quantitative insights into the dynamics of how the pandemic flu spread across different parts of the country. We discovered that the claims data exhibits multi-scale patterns from which we could identify a small number of states in the United States (US) that act as ""bridge regions"" contributing to one or more specific influenza spread patterns. Similar to previous studies, the patterns show that the south-eastern regions of the US were widely affected by the H1N1 flu pandemic. Several of these south-eastern states act as bridge regions, which connect the north-east and central US in terms of flu occurrences. CONCLUSIONS: These quantitative insights show how the claims data combined with novel analytical techniques can provide important information to decision makers when an epidemic spreads throughout the country. Taken together ORBiT provides a scalable and extensible platform for public health surveillance.",2015 Dec 7,"['Ramanathan, Arvind', 'Pullum, Laura L', 'Hobson, Tanner C', 'Steed, Chad A', 'Quinn, Shannon P', 'Chennubhotla, Chakra S', 'Valkova, Silvia']",BMC Bioinformatics,,,True
6fe8d33a03f951e2b85def26fa987ea1e98d5c0e,PMC,Assessing Ebola-related web search behaviour: insights and implications from an analytical study of Google Trends-based query volumes,http://dx.doi.org/10.1186/s40249-015-0090-9,PMC4674955,26654247,CC BY,"BACKGROUND: The 2014 Ebola epidemic in West Africa has attracted public interest worldwide, leading to millions of Ebola-related Internet searches being performed during the period of the epidemic. This study aimed to evaluate and interpret Google search queries for terms related to the Ebola outbreak both at the global level and in all countries where primary cases of Ebola occurred. The study also endeavoured to look at the correlation between the number of overall and weekly web searches and the number of overall and weekly new cases of Ebola. METHODS: Google Trends (GT) was used to explore Internet activity related to Ebola. The study period was from 29 December 2013 to 14 June 2015. Pearson’s correlation was performed to correlate Ebola-related relative search volumes (RSVs) with the number of weekly and overall Ebola cases. Multivariate regression was performed using Ebola-related RSV as a dependent variable, and the overall number of Ebola cases and the Human Development Index were used as predictor variables. RESULTS: The greatest RSV was registered in the three West African countries mainly affected by the Ebola epidemic. The queries varied in the different countries. Both quantitative and qualitative differences between the affected African countries and other Western countries with primary cases were noted, in relation to the different flux volumes and different time courses. In the affected African countries, web query search volumes were mostly concentrated in the capital areas. However, in Western countries, web queries were uniformly distributed over the national territory. In terms of the three countries mainly affected by the Ebola epidemic, the correlation between the number of new weekly cases of Ebola and the weekly GT index varied from weak to moderate. The correlation between the number of Ebola cases registered in all countries during the study period and the GT index was very high. CONCLUSION: Google Trends showed a coarse-grained nature, strongly correlating with global epidemiological data, but was weaker at country level, as it was prone to distortions induced by unbalanced media coverage and the digital divide. Global and local health agencies could usefully exploit GT data to identify disease-related information needs and plan proper communication strategies, particularly in the case of health-threatening events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-015-0090-9) contains supplementary material, which is available to authorized users.",2015 Dec 10,"['Alicino, Cristiano', 'Bragazzi, Nicola Luigi', 'Faccio, Valeria', 'Amicizia, Daniela', 'Panatto, Donatella', 'Gasparini, Roberto', 'Icardi, Giancarlo', 'Orsi, Andrea']",Infect Dis Poverty,,,False
47c38815f36cc14e7160f1890cda9f39b7e1d778,PMC,Assessing Ebola-related web search behaviour: insights and implications from an analytical study of Google Trends-based query volumes,http://dx.doi.org/10.1186/s40249-015-0090-9,PMC4674955,26654247,CC BY,"BACKGROUND: The 2014 Ebola epidemic in West Africa has attracted public interest worldwide, leading to millions of Ebola-related Internet searches being performed during the period of the epidemic. This study aimed to evaluate and interpret Google search queries for terms related to the Ebola outbreak both at the global level and in all countries where primary cases of Ebola occurred. The study also endeavoured to look at the correlation between the number of overall and weekly web searches and the number of overall and weekly new cases of Ebola. METHODS: Google Trends (GT) was used to explore Internet activity related to Ebola. The study period was from 29 December 2013 to 14 June 2015. Pearson’s correlation was performed to correlate Ebola-related relative search volumes (RSVs) with the number of weekly and overall Ebola cases. Multivariate regression was performed using Ebola-related RSV as a dependent variable, and the overall number of Ebola cases and the Human Development Index were used as predictor variables. RESULTS: The greatest RSV was registered in the three West African countries mainly affected by the Ebola epidemic. The queries varied in the different countries. Both quantitative and qualitative differences between the affected African countries and other Western countries with primary cases were noted, in relation to the different flux volumes and different time courses. In the affected African countries, web query search volumes were mostly concentrated in the capital areas. However, in Western countries, web queries were uniformly distributed over the national territory. In terms of the three countries mainly affected by the Ebola epidemic, the correlation between the number of new weekly cases of Ebola and the weekly GT index varied from weak to moderate. The correlation between the number of Ebola cases registered in all countries during the study period and the GT index was very high. CONCLUSION: Google Trends showed a coarse-grained nature, strongly correlating with global epidemiological data, but was weaker at country level, as it was prone to distortions induced by unbalanced media coverage and the digital divide. Global and local health agencies could usefully exploit GT data to identify disease-related information needs and plan proper communication strategies, particularly in the case of health-threatening events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-015-0090-9) contains supplementary material, which is available to authorized users.",2015 Dec 10,"['Alicino, Cristiano', 'Bragazzi, Nicola Luigi', 'Faccio, Valeria', 'Amicizia, Daniela', 'Panatto, Donatella', 'Gasparini, Roberto', 'Icardi, Giancarlo', 'Orsi, Andrea']",Infect Dis Poverty,,,True
803e5ac0891c5ae6a165ca754e04fcfbb6e06394,PMC,Identification of climate factors related to human infection with avian influenza A H7N9 and H5N1 viruses in China,http://dx.doi.org/10.1038/srep18094,PMC4676028,26656876,CC BY,"Human influenza infections display a strongly seasonal pattern. However, whether H7N9 and H5N1 infections correlate with climate factors has not been examined. Here, we analyzed 350 cases of H7N9 infection and 47 cases of H5N1 infection. The spatial characteristics of these cases revealed that H5N1 infections mainly occurred in the South, Middle, and Northwest of China, while the occurrence of H7N9 was concentrated in coastal areas of East and South of China. Aside from spatial-temporal characteristics, the most adaptive meteorological conditions for the occurrence of human infections by these two viral subtypes were different. We found that H7N9 infections correlate with climate factors, especially temperature (TEM) and relative humidity (RHU), while H5N1 infections correlate with TEM and atmospheric pressure (PRS). Hence, we propose a risky window (TEM 4–14 °C and RHU 65–95%) for H7N9 infection and (TEM 2–22 °C and PRS 980-1025 kPa) for H5N1 infection. Our results represent the first step in determining the effects of climate factors on two different virus infections in China and provide warning guidelines for the future when provinces fall into the risky windows. These findings revealed integrated predictive meteorological factors rooted in statistic data that enable the establishment of preventive actions and precautionary measures against future outbreaks.",2015 Dec 11,"['Li, Jing', 'Rao, Yuhan', 'Sun, Qinglan', 'Wu, Xiaoxu', 'Jin, Jiao', 'Bi, Yuhai', 'Chen, Jin', 'Lei, Fumin', 'Liu, Qiyong', 'Duan, Ziyuan', 'Ma, Juncai', 'Gao, George F.', 'Liu, Di', 'Liu, Wenjun']",Sci Rep,,,True
3e77f816d34625139df9452b46df14df6726b390,PMC,Identification of climate factors related to human infection with avian influenza A H7N9 and H5N1 viruses in China,http://dx.doi.org/10.1038/srep18094,PMC4676028,26656876,CC BY,"Human influenza infections display a strongly seasonal pattern. However, whether H7N9 and H5N1 infections correlate with climate factors has not been examined. Here, we analyzed 350 cases of H7N9 infection and 47 cases of H5N1 infection. The spatial characteristics of these cases revealed that H5N1 infections mainly occurred in the South, Middle, and Northwest of China, while the occurrence of H7N9 was concentrated in coastal areas of East and South of China. Aside from spatial-temporal characteristics, the most adaptive meteorological conditions for the occurrence of human infections by these two viral subtypes were different. We found that H7N9 infections correlate with climate factors, especially temperature (TEM) and relative humidity (RHU), while H5N1 infections correlate with TEM and atmospheric pressure (PRS). Hence, we propose a risky window (TEM 4–14 °C and RHU 65–95%) for H7N9 infection and (TEM 2–22 °C and PRS 980-1025 kPa) for H5N1 infection. Our results represent the first step in determining the effects of climate factors on two different virus infections in China and provide warning guidelines for the future when provinces fall into the risky windows. These findings revealed integrated predictive meteorological factors rooted in statistic data that enable the establishment of preventive actions and precautionary measures against future outbreaks.",2015 Dec 11,"['Li, Jing', 'Rao, Yuhan', 'Sun, Qinglan', 'Wu, Xiaoxu', 'Jin, Jiao', 'Bi, Yuhai', 'Chen, Jin', 'Lei, Fumin', 'Liu, Qiyong', 'Duan, Ziyuan', 'Ma, Juncai', 'Gao, George F.', 'Liu, Di', 'Liu, Wenjun']",Sci Rep,,,False
dbd589ba5a6b57f60ccafcf475c57a88211ff95e,PMC,"Genomic legacy of the African cheetah, Acinonyx jubatus",http://dx.doi.org/10.1186/s13059-015-0837-4,PMC4676127,26653294,CC BY,"BACKGROUND: Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations. RESULTS: Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084–12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (p<0.02), a gene mediating spermatozoon development, indicates cheetah fixation of five function-damaging amino acid variants distinct from AKAP4 homologues of other Felidae or mammals; AKAP4 dysfunction may cause the cheetah’s extremely high (>80 %) pleiomorphic sperm. CONCLUSIONS: The study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species’ natural history, physiological adaptations and unique reproductive disposition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0837-4) contains supplementary material, which is available to authorized users.",2015 Dec 10,"['Dobrynin, Pavel', 'Liu, Shiping', 'Tamazian, Gaik', 'Xiong, Zijun', 'Yurchenko, Andrey A.', 'Krasheninnikova, Ksenia', 'Kliver, Sergey', 'Schmidt-Küntzel, Anne', 'Koepfli, Klaus-Peter', 'Johnson, Warren', 'Kuderna, Lukas F.K.', 'García-Pérez, Raquel', 'Manuel, Marc de', 'Godinez, Ricardo', 'Komissarov, Aleksey', 'Makunin, Alexey', 'Brukhin, Vladimir', 'Qiu, Weilin', 'Zhou, Long', 'Li, Fang', 'Yi, Jian', 'Driscoll, Carlos', 'Antunes, Agostinho', 'Oleksyk, Taras K.', 'Eizirik, Eduardo', 'Perelman, Polina', 'Roelke, Melody', 'Wildt, David', 'Diekhans, Mark', 'Marques-Bonet, Tomas', 'Marker, Laurie', 'Bhak, Jong', 'Wang, Jun', 'Zhang, Guojie', 'O’Brien, Stephen J.']",Genome Biol,,,True
20c2e99b2e557513c61d82a9d291b809eafaf70e,PMC,"Genomic legacy of the African cheetah, Acinonyx jubatus",http://dx.doi.org/10.1186/s13059-015-0837-4,PMC4676127,26653294,CC BY,"BACKGROUND: Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations. RESULTS: Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084–12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (p<0.02), a gene mediating spermatozoon development, indicates cheetah fixation of five function-damaging amino acid variants distinct from AKAP4 homologues of other Felidae or mammals; AKAP4 dysfunction may cause the cheetah’s extremely high (>80 %) pleiomorphic sperm. CONCLUSIONS: The study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species’ natural history, physiological adaptations and unique reproductive disposition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0837-4) contains supplementary material, which is available to authorized users.",2015 Dec 10,"['Dobrynin, Pavel', 'Liu, Shiping', 'Tamazian, Gaik', 'Xiong, Zijun', 'Yurchenko, Andrey A.', 'Krasheninnikova, Ksenia', 'Kliver, Sergey', 'Schmidt-Küntzel, Anne', 'Koepfli, Klaus-Peter', 'Johnson, Warren', 'Kuderna, Lukas F.K.', 'García-Pérez, Raquel', 'Manuel, Marc de', 'Godinez, Ricardo', 'Komissarov, Aleksey', 'Makunin, Alexey', 'Brukhin, Vladimir', 'Qiu, Weilin', 'Zhou, Long', 'Li, Fang', 'Yi, Jian', 'Driscoll, Carlos', 'Antunes, Agostinho', 'Oleksyk, Taras K.', 'Eizirik, Eduardo', 'Perelman, Polina', 'Roelke, Melody', 'Wildt, David', 'Diekhans, Mark', 'Marques-Bonet, Tomas', 'Marker, Laurie', 'Bhak, Jong', 'Wang, Jun', 'Zhang, Guojie', 'O’Brien, Stephen J.']",Genome Biol,,,True
df794557c0c0da0a84d28c5df7f3748560fde11f,PMC,"Genomic legacy of the African cheetah, Acinonyx jubatus",http://dx.doi.org/10.1186/s13059-015-0837-4,PMC4676127,26653294,CC BY,"BACKGROUND: Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations. RESULTS: Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084–12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (p<0.02), a gene mediating spermatozoon development, indicates cheetah fixation of five function-damaging amino acid variants distinct from AKAP4 homologues of other Felidae or mammals; AKAP4 dysfunction may cause the cheetah’s extremely high (>80 %) pleiomorphic sperm. CONCLUSIONS: The study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species’ natural history, physiological adaptations and unique reproductive disposition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0837-4) contains supplementary material, which is available to authorized users.",2015 Dec 10,"['Dobrynin, Pavel', 'Liu, Shiping', 'Tamazian, Gaik', 'Xiong, Zijun', 'Yurchenko, Andrey A.', 'Krasheninnikova, Ksenia', 'Kliver, Sergey', 'Schmidt-Küntzel, Anne', 'Koepfli, Klaus-Peter', 'Johnson, Warren', 'Kuderna, Lukas F.K.', 'García-Pérez, Raquel', 'Manuel, Marc de', 'Godinez, Ricardo', 'Komissarov, Aleksey', 'Makunin, Alexey', 'Brukhin, Vladimir', 'Qiu, Weilin', 'Zhou, Long', 'Li, Fang', 'Yi, Jian', 'Driscoll, Carlos', 'Antunes, Agostinho', 'Oleksyk, Taras K.', 'Eizirik, Eduardo', 'Perelman, Polina', 'Roelke, Melody', 'Wildt, David', 'Diekhans, Mark', 'Marques-Bonet, Tomas', 'Marker, Laurie', 'Bhak, Jong', 'Wang, Jun', 'Zhang, Guojie', 'O’Brien, Stephen J.']",Genome Biol,,,True
9538da236dd88828d491e85addc5b2c6669e7c5a,PMC,Burden of respiratory syncytial virus infections in China: Systematic review and meta–analysis,http://dx.doi.org/10.7189/jogh.05.020417,PMC4676581,26682049,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of acute respiratory tract infection (ARTI) related morbidity and mortality worldwide. However, the disease burden due to RSV has not been systematically summarized in China. METHOD: A systematic search was performed in the Chinese BioMedical Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and PubMed to identify available published RSV studies in China. RESULTS: A total of 489 641 patients with ARTIs from 135 studies were included in the analysis. Among patients with ARTIs, RSV accounted for 18.7% (95% confidence interval CI 17.1–20.5%). The prevalence of RSV was highest in infants (26.5%, 95% CI 23.7–29.5%) and lowest in those aged ≥16 years (2.8%, 95% CI 1.3–6.1). A higher prevalence of RSV was seen in inpatients (22%, 95% CI 19.9–24.2%) than in outpatients (14%, 95% CI 9.6–19.9%). RSV type A accounted for 63.1% (95% CI 52.3–72.8%) of all RSV infections. RSV infections occurred mainly in winter and spring. The most common clinical manifestations were cough, production of sputum, wheezing and fever. CONCLUSION: RSV is the leading cause of viral ARTIs in China, particularly in infants and young children. Our findings are valuable for guiding the selection of appropriate therapies for ARTIs and implementation of preventive measures against RSV infections. Our data further supports the development of a successful RSV vaccine as a high priority.",,"['Zhang, Yaowen', 'Yuan, Lichao', 'Zhang, Yongming', 'Zhang, Xiuping', 'Zheng, Minghuan', 'Kyaw, Moe H']",J Glob Health.; 5(2):020417,,,True
0851abc9f5ae5d1c1225f665b8ddd13a7c905179,PMC,Burden of respiratory syncytial virus infections in China: Systematic review and meta–analysis,http://dx.doi.org/10.7189/jogh.05.020417,PMC4676581,26682049,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of acute respiratory tract infection (ARTI) related morbidity and mortality worldwide. However, the disease burden due to RSV has not been systematically summarized in China. METHOD: A systematic search was performed in the Chinese BioMedical Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and PubMed to identify available published RSV studies in China. RESULTS: A total of 489 641 patients with ARTIs from 135 studies were included in the analysis. Among patients with ARTIs, RSV accounted for 18.7% (95% confidence interval CI 17.1–20.5%). The prevalence of RSV was highest in infants (26.5%, 95% CI 23.7–29.5%) and lowest in those aged ≥16 years (2.8%, 95% CI 1.3–6.1). A higher prevalence of RSV was seen in inpatients (22%, 95% CI 19.9–24.2%) than in outpatients (14%, 95% CI 9.6–19.9%). RSV type A accounted for 63.1% (95% CI 52.3–72.8%) of all RSV infections. RSV infections occurred mainly in winter and spring. The most common clinical manifestations were cough, production of sputum, wheezing and fever. CONCLUSION: RSV is the leading cause of viral ARTIs in China, particularly in infants and young children. Our findings are valuable for guiding the selection of appropriate therapies for ARTIs and implementation of preventive measures against RSV infections. Our data further supports the development of a successful RSV vaccine as a high priority.",,"['Zhang, Yaowen', 'Yuan, Lichao', 'Zhang, Yongming', 'Zhang, Xiuping', 'Zheng, Minghuan', 'Kyaw, Moe H']",J Glob Health.; 5(2):020417,,,False
e88797458f110553b9418007d35401975dce1454,PMC,Respiratory Syncytial Virus Uses CX3CR1 as a Receptor on Primary Human Airway Epithelial Cultures,http://dx.doi.org/10.1371/journal.ppat.1005318,PMC4676609,26658574,CC BY,"Respiratory syncytial virus (RSV) is the most frequent cause of lower respiratory disease in infants, but no vaccine or effective therapy is available. The initiation of RSV infection of immortalized cells is largely dependent on cell surface heparan sulfate (HS), a receptor for the RSV attachment (G) glycoprotein in immortalized cells. However, RSV infects the ciliated cells in primary well differentiated human airway epithelial (HAE) cultures via the apical surface, but HS is not detectable on this surface. Here we show that soluble HS inhibits infection of immortalized cells, but not HAE cultures, confirming that HS is not the receptor on HAE cultures. Conversely, a “non-neutralizing” monoclonal antibody against the G protein that does not block RSV infection of immortalized cells, does inhibit infection of HAE cultures. This antibody was previously shown to block the interaction between the G protein and the chemokine receptor CX3CR1 and we have mapped the binding site for this antibody to the CX3C motif and its surrounding region in the G protein. We show that CX3CR1 is present on the apical surface of ciliated cells in HAE cultures and especially on the cilia. RSV infection of HAE cultures is reduced by an antibody against CX3CR1 and by mutations in the G protein CX3C motif. Additionally, mice lacking CX3CR1 are less susceptible to RSV infection. These findings demonstrate that RSV uses CX3CR1 as a cellular receptor on HAE cultures and highlight the importance of using a physiologically relevant model to study virus entry and antibody neutralization.",2015 Dec 11,"['Johnson, Sara M.', 'McNally, Beth A.', 'Ioannidis, Ioannis', 'Flano, Emilio', 'Teng, Michael N.', 'Oomens, Antonius G.', 'Walsh, Edward E.', 'Peeples, Mark E.']",PLoS Pathog,,,True
b4e98770894089e276f91c1d00e58c8885708e11,PMC,Evaluation of a combined MxA and CRP point-of-care immunoassay to identify viral and/or bacterial immune response in patients with acute febrile respiratory infection,http://dx.doi.org/10.3402/ecrj.v2.28245,PMC4676840,26672961,CC BY,"BACKGROUND: Challenges in the clinical differentiation of viral and/or bacterial respiratory infection lead to the misappropriation of antibiotics and increased healthcare costs. A tool to facilitate rapid and accurate point-of-care (POC) differentiation is needed. METHODS AND FINDINGS: A prospective, single center, blinded, observational clinical trial was conducted at Beth Israel Deaconess Medical Center from December 2012 to August 2013 to determine the accuracy of a POC immunoassay to identify a clinically significant immune response to viral and/or bacterial infection. Sixty patients with acute febrile respiratory infection (19 pharyngitis and 41 lower respiratory tract infection [LRTI]) were enrolled. Participants provided fingerstick blood for immunoassay testing (myxovirus A [MxA] and c-reactive protein [CRP]) and four oropharyngeal samples for viral PCR and routine bacterial cell culture. A venous blood sample was collected. An ELISA was used to measure CRP and MxA. Paired serological testing was used to confirm atypical bacteria. A urine sample was provided for Streptococcus and Legionella antigen testing. Patients with suspected LRTI had sputum and blood cultures, chest X-ray, and WBC count measured. Viral infection was confirmed if oropharyngeal PCR was positive for viral pathogens. Bacterial infection was confirmed in positive throat or sputum cultures. Elevated immunoglobulin M antibodies or twofold increase in IgG antibodies between acute and convalescent phase indicated atypical bacteria. Positive Streptococcus or Legionella urine antigen assays also confirmed bacterial infection. The immunoassay correctly categorized subjects as 92% (22/24) negative, 80% (16/20) with bacterial infection, and 70% (7/10) with viral infection. CONCLUSIONS: The interplay between an MxA value and a semi-quantitative CRP value can aid in the differentiation of infectious etiology. In isolation, neither MxA nor CRP alone is sensitive or specific. However, the pattern of results in a rapid immunoassay provides a sensitive and specific method to differentiate acute febrile respiratory infections. This diagnostic information may help reduce antibiotic misuse and resistance and lower healthcare costs.",2015 Dec 10,"['Sambursky, Robert', 'Shapiro, Nathan']",Eur Clin Respir J,,,True
7cb443aaa8612c98630f7ecc02ec070a547f4d9f,PMC,Evaluation of a combined MxA and CRP point-of-care immunoassay to identify viral and/or bacterial immune response in patients with acute febrile respiratory infection,http://dx.doi.org/10.3402/ecrj.v2.28245,PMC4676840,26672961,CC BY,"BACKGROUND: Challenges in the clinical differentiation of viral and/or bacterial respiratory infection lead to the misappropriation of antibiotics and increased healthcare costs. A tool to facilitate rapid and accurate point-of-care (POC) differentiation is needed. METHODS AND FINDINGS: A prospective, single center, blinded, observational clinical trial was conducted at Beth Israel Deaconess Medical Center from December 2012 to August 2013 to determine the accuracy of a POC immunoassay to identify a clinically significant immune response to viral and/or bacterial infection. Sixty patients with acute febrile respiratory infection (19 pharyngitis and 41 lower respiratory tract infection [LRTI]) were enrolled. Participants provided fingerstick blood for immunoassay testing (myxovirus A [MxA] and c-reactive protein [CRP]) and four oropharyngeal samples for viral PCR and routine bacterial cell culture. A venous blood sample was collected. An ELISA was used to measure CRP and MxA. Paired serological testing was used to confirm atypical bacteria. A urine sample was provided for Streptococcus and Legionella antigen testing. Patients with suspected LRTI had sputum and blood cultures, chest X-ray, and WBC count measured. Viral infection was confirmed if oropharyngeal PCR was positive for viral pathogens. Bacterial infection was confirmed in positive throat or sputum cultures. Elevated immunoglobulin M antibodies or twofold increase in IgG antibodies between acute and convalescent phase indicated atypical bacteria. Positive Streptococcus or Legionella urine antigen assays also confirmed bacterial infection. The immunoassay correctly categorized subjects as 92% (22/24) negative, 80% (16/20) with bacterial infection, and 70% (7/10) with viral infection. CONCLUSIONS: The interplay between an MxA value and a semi-quantitative CRP value can aid in the differentiation of infectious etiology. In isolation, neither MxA nor CRP alone is sensitive or specific. However, the pattern of results in a rapid immunoassay provides a sensitive and specific method to differentiate acute febrile respiratory infections. This diagnostic information may help reduce antibiotic misuse and resistance and lower healthcare costs.",2015 Dec 10,"['Sambursky, Robert', 'Shapiro, Nathan']",Eur Clin Respir J,,,False
8bf449477aff84ef0591f10731a654610a5126b7,PMC,Gene silencing of TACE enhances plaque stability and improves vascular remodeling in a rabbit model of atherosclerosis,http://dx.doi.org/10.1038/srep17939,PMC4677302,26655882,CC BY,"We aimed to test the hypothesis that gene silencing of tumor necrosis factor alpha converting enzyme (TACE) may attenuate lesion inflammation and positive vascular remodeling and enhance plaque stability in a rabbit model of atherosclerosis. Lentivirus-mediated TACE shRNA was injected into the abdominal aortic plaques of rabbits which effectively down-regulated TACE expression and activities from week 8 to week 16. TACE gene silencing reduced remodeling index and plaque burden, and diminished the content of macrophages and lipids while increased that of smooth muscle cells and collagen in the aortic plaques. In addition, TACE gene silencing attenuated the local expression of P65, iNOS, ICAM-1, VEGF and Flt-1 and activities of MMP9 and MMP2 while increased the local expression of TGF-β1 together with reduced number of neovessels in the aorta. TACE shRNA treatment resulted in down-regulated expression of TACE in macrophages and blunted ERK-P38 phosphorylation and tube formation of co-cultured mouse vascular smooth muscle cells or human umbilical vein endothelial cells. In conclusion, gene silencing of TACE enhanced plaque stability and improved vascular positive remodeling. The mechanisms may involve attenuated local inflammation, neovascularization and MMP activation, as well as enhanced collagen production probably via down-regulated ERK-NF-κB and up-regulated TGF-β1 signaling pathways.",2015 Dec 14,"['Zhao, Xueqiang', 'Kong, Jing', 'Zhao, Yuxia', 'Wang, Xuping', 'Bu, Peili', 'Zhang, Cheng', 'Zhang, Yun']",Sci Rep,,,True
1412106d8254d159356dda94db652655e51bd729,PMC,CVTree3 Web Server for Whole-genome-based and Alignment-free Prokaryotic Phylogeny and Taxonomy,http://dx.doi.org/10.1016/j.gpb.2015.08.004,PMC4678791,26563468,CC BY,"A faithful phylogeny and an objective taxonomy for prokaryotes should agree with each other and ultimately follow the genome data. With the number of sequenced genomes reaching tens of thousands, both tree inference and detailed comparison with taxonomy are great challenges. We now provide one solution in the latest Release 3.0 of the alignment-free and whole-genome-based web server CVTree3. The server resides in a cluster of 64 cores and is equipped with an interactive, collapsible, and expandable tree display. It is capable of comparing the tree branching order with prokaryotic classification at all taxonomic ranks from domains down to species and strains. CVTree3 allows for inquiry by taxon names and trial on lineage modifications. In addition, it reports a summary of monophyletic and non-monophyletic taxa at all ranks as well as produces print-quality subtree figures. After giving an overview of retrospective verification of the CVTree approach, the power of the new server is described for the mega-classification of prokaryotes and determination of taxonomic placement of some newly-sequenced genomes. A few discrepancies between CVTree and 16S rRNA analyses are also summarized with regard to possible taxonomic revisions. CVTree3 is freely accessible to all users at http://tlife.fudan.edu.cn/cvtree3/ without login requirements.",2015 Oct 10,"['Zuo, Guanghong', 'Hao, Bailin']",Genomics Proteomics Bioinformatics,,,False
8f9fb1b2ed8b56d2524c9cf458277e377711397c,PMC,CVTree3 Web Server for Whole-genome-based and Alignment-free Prokaryotic Phylogeny and Taxonomy,http://dx.doi.org/10.1016/j.gpb.2015.08.004,PMC4678791,26563468,CC BY,"A faithful phylogeny and an objective taxonomy for prokaryotes should agree with each other and ultimately follow the genome data. With the number of sequenced genomes reaching tens of thousands, both tree inference and detailed comparison with taxonomy are great challenges. We now provide one solution in the latest Release 3.0 of the alignment-free and whole-genome-based web server CVTree3. The server resides in a cluster of 64 cores and is equipped with an interactive, collapsible, and expandable tree display. It is capable of comparing the tree branching order with prokaryotic classification at all taxonomic ranks from domains down to species and strains. CVTree3 allows for inquiry by taxon names and trial on lineage modifications. In addition, it reports a summary of monophyletic and non-monophyletic taxa at all ranks as well as produces print-quality subtree figures. After giving an overview of retrospective verification of the CVTree approach, the power of the new server is described for the mega-classification of prokaryotes and determination of taxonomic placement of some newly-sequenced genomes. A few discrepancies between CVTree and 16S rRNA analyses are also summarized with regard to possible taxonomic revisions. CVTree3 is freely accessible to all users at http://tlife.fudan.edu.cn/cvtree3/ without login requirements.",2015 Oct 10,"['Zuo, Guanghong', 'Hao, Bailin']",Genomics Proteomics Bioinformatics,,,False
5706247afd9585354f3dae2f70d200a25f8e3f4c,PMC,"Discovery of novel virus sequences in an isolated and threatened bat species, the New Zealand lesser short-tailed bat (Mystacina tuberculata)",http://dx.doi.org/10.1099/vir.0.000158,PMC4681071,25900137,CC BY,"Bats harbour a diverse array of viruses, including significant human pathogens. Extensive metagenomic studies of material from bats, in particular guano, have revealed a large number of novel or divergent viral taxa that were previously unknown. New Zealand has only two extant indigenous terrestrial mammals, which are both bats, Mystacina tuberculata (the lesser short-tailed bat) and Chalinolobus tuberculatus (the long-tailed bat). Until the human introduction of exotic mammals, these species had been isolated from all other terrestrial mammals for over 1 million years (potentially over 16 million years for M. tuberculata). Four bat guano samples were collected from M. tuberculata roosts on the isolated offshore island of Whenua hou (Codfish Island) in New Zealand. Metagenomic analysis revealed that this species still hosts a plethora of divergent viruses. Whilst the majority of viruses detected were likely to be of dietary origin, some putative vertebrate virus sequences were identified. Papillomavirus, polyomavirus, calicivirus and hepevirus were found in the metagenomic data and subsequently confirmed using independent PCR assays and sequencing. The new hepevirus and calicivirus sequences may represent new genera within these viral families. Our findings may provide an insight into the origins of viral families, given their detection in an isolated host species.",2015 Aug,"['Wang, Jing', 'Moore, Nicole E.', 'Murray, Zak L.', 'McInnes, Kate', 'White, Daniel J.', 'Tompkins, Daniel M.', 'Hall, Richard J.']",J Gen Virol,,,True
2ed563bcb94b0dd5bb3081be75d5173c447e7314,PMC,"Discovery of novel virus sequences in an isolated and threatened bat species, the New Zealand lesser short-tailed bat (Mystacina tuberculata)",http://dx.doi.org/10.1099/vir.0.000158,PMC4681071,25900137,CC BY,"Bats harbour a diverse array of viruses, including significant human pathogens. Extensive metagenomic studies of material from bats, in particular guano, have revealed a large number of novel or divergent viral taxa that were previously unknown. New Zealand has only two extant indigenous terrestrial mammals, which are both bats, Mystacina tuberculata (the lesser short-tailed bat) and Chalinolobus tuberculatus (the long-tailed bat). Until the human introduction of exotic mammals, these species had been isolated from all other terrestrial mammals for over 1 million years (potentially over 16 million years for M. tuberculata). Four bat guano samples were collected from M. tuberculata roosts on the isolated offshore island of Whenua hou (Codfish Island) in New Zealand. Metagenomic analysis revealed that this species still hosts a plethora of divergent viruses. Whilst the majority of viruses detected were likely to be of dietary origin, some putative vertebrate virus sequences were identified. Papillomavirus, polyomavirus, calicivirus and hepevirus were found in the metagenomic data and subsequently confirmed using independent PCR assays and sequencing. The new hepevirus and calicivirus sequences may represent new genera within these viral families. Our findings may provide an insight into the origins of viral families, given their detection in an isolated host species.",2015 Aug,"['Wang, Jing', 'Moore, Nicole E.', 'Murray, Zak L.', 'McInnes, Kate', 'White, Daniel J.', 'Tompkins, Daniel M.', 'Hall, Richard J.']",J Gen Virol,,,False
51f8792fd26cd2c094c1b2d0e5539902fb6221da,PMC,People at Risk of Influenza Pandemics: The Evolution of Perception and Behavior,http://dx.doi.org/10.1371/journal.pone.0144868,PMC4682843,26658371,CC BY,"Influenza pandemics can severely impact human health and society. Understanding public perception and behavior toward influenza pandemics is important for minimizing the effects of such events. Public perception and behavior are expected to change over the course of an influenza pandemic, but this idea has received little attention in previous studies. Our study aimed to understand the dynamics of public perception and behavior over the course of the 2009 H1N1 influenza pandemic. Three consecutive cross-sectional surveys were administered among Beijing residents with random-digit dialing techniques in March 2008 and August and November 2009. Effective samples of 507, 508 and 1006 respondents were interviewed in each of the three surveys, respectively. The mean scores of risk perception were low to moderate across the three surveys. The perceived risk of infection of self was significantly lower than that of the community, revealing an optimistic bias. Longitudinally, the perceived risk of contracting H1N1 increased, whereas the perceived risk of being unable to obtain medicine and medical care once influenza permeated the community first increased and then decreased. Responsive actions toward influenza varied. Most respondents took actions that required little extra effort, such as ventilating rooms; these actions did not change over time. Comparatively, a smaller number of respondents took actions for coping with influenza, such as vaccination; however, these actions were taken by an increasing number of respondents over time. The association between risk perception and behavior was unstable. Positive, insignificant, and negative associations were obtained in the three surveys. In conclusion, the evolving patterns of risk perception and responsive behavior over the course of an influenza pandemic are sensitive to how risk and behavior are defined and scoped.",2015 Dec 14,"['Xu, Jianhua', 'Peng, Zongchao']",PLoS One,,,True
ff986fb85af07d524411d6eb829e38be349df839,PMC,Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease,http://dx.doi.org/10.1371/journal.pone.0144865,PMC4682845,26658006,CC BY,"BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.",2015 Dec 14,"['Ho, Bo-Lin', 'Cheng, Shu-Chun', 'Shi, Lin', 'Wang, Ting-Yun', 'Ho, Kuan-I', 'Chou, Chi-Yuan']",PLoS One,,,True
ae6f4f9bdd17413b0378597482f695394c48d599,PMC,Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease,http://dx.doi.org/10.1371/journal.pone.0144865,PMC4682845,26658006,CC BY,"BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.",2015 Dec 14,"['Ho, Bo-Lin', 'Cheng, Shu-Chun', 'Shi, Lin', 'Wang, Ting-Yun', 'Ho, Kuan-I', 'Chou, Chi-Yuan']",PLoS One,,,False
791960717d653a8c50cefae61dd7390fed9a2af3,PMC,Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease,http://dx.doi.org/10.1371/journal.pone.0144865,PMC4682845,26658006,CC BY,"BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.",2015 Dec 14,"['Ho, Bo-Lin', 'Cheng, Shu-Chun', 'Shi, Lin', 'Wang, Ting-Yun', 'Ho, Kuan-I', 'Chou, Chi-Yuan']",PLoS One,,,False
c38b3a8cc344708e05fd6e696cb2f05372c45fbe,PMC,Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease,http://dx.doi.org/10.1371/journal.pone.0144865,PMC4682845,26658006,CC BY,"BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.",2015 Dec 14,"['Ho, Bo-Lin', 'Cheng, Shu-Chun', 'Shi, Lin', 'Wang, Ting-Yun', 'Ho, Kuan-I', 'Chou, Chi-Yuan']",PLoS One,,,False
fa4e07fc8a5200929c2299116a7784db01fafed0,PMC,Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease,http://dx.doi.org/10.1371/journal.pone.0144865,PMC4682845,26658006,CC BY,"BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.",2015 Dec 14,"['Ho, Bo-Lin', 'Cheng, Shu-Chun', 'Shi, Lin', 'Wang, Ting-Yun', 'Ho, Kuan-I', 'Chou, Chi-Yuan']",PLoS One,,,False
ac2ef63ed042c4a98bd5d61a5a65ac535705a49f,PMC,Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease,http://dx.doi.org/10.1371/journal.pone.0144865,PMC4682845,26658006,CC BY,"BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.",2015 Dec 14,"['Ho, Bo-Lin', 'Cheng, Shu-Chun', 'Shi, Lin', 'Wang, Ting-Yun', 'Ho, Kuan-I', 'Chou, Chi-Yuan']",PLoS One,,,False
99eb640f565313af87f99b81f438b833002ba272,PMC,Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease,http://dx.doi.org/10.1371/journal.pone.0144865,PMC4682845,26658006,CC BY,"BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.",2015 Dec 14,"['Ho, Bo-Lin', 'Cheng, Shu-Chun', 'Shi, Lin', 'Wang, Ting-Yun', 'Ho, Kuan-I', 'Chou, Chi-Yuan']",PLoS One,,,False
73962bb05d0fa45657756857801fbb3f9e139b04,PMC,TGF-βI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis,http://dx.doi.org/10.1371/journal.pone.0145256,PMC4682958,26675296,CC BY,"Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-β receptor I (TGF-β RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-β RI and OCT4, and either TGF-β RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-βI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-βI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-βI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-βI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-β plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell migration. These findings would be useful for developing therapeutic strategies targeting TGF-β-OCT4 signaling to prevent endometriosis in the future.",2015 Dec 16,"['Au, Heng-Kien', 'Chang, Jui-Hung', 'Wu, Yu-Chih', 'Kuo, Yung-Che', 'Chen, Yu-Hsi', 'Lee, Wei-Chin', 'Chang, Te-Sheng', 'Lan, Pei-Chi', 'Kuo, Hung-Chih', 'Lee, Kha-Liang', 'Lee, Mei-Tsu', 'Tzeng, Chii-Ruey', 'Huang, Yen-Hua']",PLoS One,,,True
805edd3fe7b8a903e0c308d2d70a941e5d8e00fd,PMC,TGF-βI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis,http://dx.doi.org/10.1371/journal.pone.0145256,PMC4682958,26675296,CC BY,"Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-β receptor I (TGF-β RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-β RI and OCT4, and either TGF-β RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-βI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-βI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-βI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-βI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-β plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell migration. These findings would be useful for developing therapeutic strategies targeting TGF-β-OCT4 signaling to prevent endometriosis in the future.",2015 Dec 16,"['Au, Heng-Kien', 'Chang, Jui-Hung', 'Wu, Yu-Chih', 'Kuo, Yung-Che', 'Chen, Yu-Hsi', 'Lee, Wei-Chin', 'Chang, Te-Sheng', 'Lan, Pei-Chi', 'Kuo, Hung-Chih', 'Lee, Kha-Liang', 'Lee, Mei-Tsu', 'Tzeng, Chii-Ruey', 'Huang, Yen-Hua']",PLoS One,,,False
498b458b57e491d5af55dc351d3c11f8bc437bb0,PMC,TGF-βI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis,http://dx.doi.org/10.1371/journal.pone.0145256,PMC4682958,26675296,CC BY,"Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-β receptor I (TGF-β RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-β RI and OCT4, and either TGF-β RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-βI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-βI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-βI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-βI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-β plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell migration. These findings would be useful for developing therapeutic strategies targeting TGF-β-OCT4 signaling to prevent endometriosis in the future.",2015 Dec 16,"['Au, Heng-Kien', 'Chang, Jui-Hung', 'Wu, Yu-Chih', 'Kuo, Yung-Che', 'Chen, Yu-Hsi', 'Lee, Wei-Chin', 'Chang, Te-Sheng', 'Lan, Pei-Chi', 'Kuo, Hung-Chih', 'Lee, Kha-Liang', 'Lee, Mei-Tsu', 'Tzeng, Chii-Ruey', 'Huang, Yen-Hua']",PLoS One,,,False
713fce03f461b2c103732cff207a5de11bb69125,PMC,TGF-βI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis,http://dx.doi.org/10.1371/journal.pone.0145256,PMC4682958,26675296,CC BY,"Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-β receptor I (TGF-β RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-β RI and OCT4, and either TGF-β RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-βI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-βI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-βI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-βI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-β plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell migration. These findings would be useful for developing therapeutic strategies targeting TGF-β-OCT4 signaling to prevent endometriosis in the future.",2015 Dec 16,"['Au, Heng-Kien', 'Chang, Jui-Hung', 'Wu, Yu-Chih', 'Kuo, Yung-Che', 'Chen, Yu-Hsi', 'Lee, Wei-Chin', 'Chang, Te-Sheng', 'Lan, Pei-Chi', 'Kuo, Hung-Chih', 'Lee, Kha-Liang', 'Lee, Mei-Tsu', 'Tzeng, Chii-Ruey', 'Huang, Yen-Hua']",PLoS One,,,False
1dcfe803d2660b1fdfa8006aace78d485512e156,PMC,"Structural and Functional Insights into Small, Glutamine-Rich, Tetratricopeptide Repeat Protein Alpha",http://dx.doi.org/10.3389/fmolb.2015.00071,PMC4683186,26734616,CC BY,"The small glutamine-rich, tetratricopeptide repeat-containing protein alpha (SGTA) is an emerging player in the quality control of secretory and membrane proteins mislocalized to the cytosol, with established roles in tail-anchored (TA) membrane protein biogenesis. SGTA consists of three structural domains with individual functions, an N-terminal dimerization domain that assists protein sorting pathways, a central tetratricopeptide repeat (TPR) domain that mediates interactions with heat-shock proteins, proteasomal, and hormonal receptors, and viral proteins, and a C-terminal glutamine rich region that binds hydrophobic substrates. SGTA has been linked to viral lifecycles and hormone receptor signaling, with implications in the pathogenesis of various disease states. Thus far, a range of biophysical techniques have been employed to characterize SGTA structure in some detail, and to investigate its interactions with binding partners in different biological contexts. A complete description of SGTA structure, together with further investigation into its function as a co-chaperone involved quality control, could provide us with useful insights into its role in maintaining cellular proteostasis, and broaden our understanding of mechanisms underlying associated pathologies. This review describes how some structural features of SGTA have been elucidated, and what this has uncovered about its cellular functions. A brief background on the structure and function of SGTA is given, highlighting its importance to biomedicine and related fields. The current level of knowledge and what remains to be understood about the structure and function of SGTA is summarized, discussing the potential direction of future research.",2015 Dec 18,"['Roberts, Joanna D.', 'Thapaliya, Arjun', 'Martínez-Lumbreras, Santiago', 'Krysztofinska, Ewelina M.', 'Isaacson, Rivka L.']",Front Mol Biosci,,,True
963cc6ca5e9eecf735dfcb89e2320a22fa4bcec6,PMC,Complete Genome Sequence of the Porcine Epidemic Diarrhea Virus Variant CH/HNYF/2014,http://dx.doi.org/10.1128/genomeA.01486-15,PMC4683238,26679593,CC BY,"Sow’s milk is a potential route for the vertical transmission of porcine epidemic diarrhea virus (PEDV) from sow to suckling piglet. We report here the complete genome sequence of PEDV strain CH/HNYF/2014, which was isolated from milk samples. This information provides further understanding of the transmission mechanisms and genetic diversity of PEDV.",2015 Dec 17,"['Li, Renfeng', 'Tian, Xiangqin', 'Qiao, Songlin', 'Guo, Junqing', 'Xie, Weitao', 'Zhang, Gaiping']",Genome Announc,,,True
85bf8bcd3494765f259e8903ed153dff0ff40a4f,PMC,TMV mutants with poly(A) tracts of different lengths demonstrate structural variations in 3′UTR affecting viral RNAs accumulation and symptom expression,http://dx.doi.org/10.1038/srep18412,PMC4683447,26678425,CC BY,"The upstream pseudoknots domain (UPD) of Tobacco mosaic virus (TMV) is located at the 3′-untranslated region (UTR). It plays an important role in virus replication and translation. To determine the importance of UPD and 3′-UTR, and the effects of introduced RNA elements in TMV 3′-UTR, a series of TMV mutants with internal poly(A) tract upstream of UPD was constructed for structural analysis by selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE). TMV(24A+UPD) and TMV(42A+UPD) formed a similar structure as that of TMV 3′-UTR, but TMV(62A+UPD) structures altered by the introduced poly(A) tract. In addition, TMV(24A+UPD) had a higher viral RNAs accumulation than TMV in N. benthamiana protoplasts, and induced lethal symptoms in the infected plants. TMV(62A+UPD) showed a drastically reduced accumulation, its coat protein was undetectable in protoplasts, and the inoculated plants remained symptomless. This study analyzed the structures of 3′-UTR of TMV and found that the longer poly(A) tract introduced upstream of UPD reduced viral RNAs accumulation and induced milder symptoms in N. benthamiana. In conclusion, different lengths of the internal poly(A) tract introduced into the TMV 3′UTR lead to structural variations that affect virus accumulation and symptom expression.",2015 Dec 18,"['Guo, Song', 'Kierzek, Elzbieta', 'Chen, Gang', 'Zhou, Yi-Jun', 'Wong, Sek-Man']",Sci Rep,,,True
30c28ceb7614a39d2950cb866b82a062254333cc,PMC,TMV mutants with poly(A) tracts of different lengths demonstrate structural variations in 3′UTR affecting viral RNAs accumulation and symptom expression,http://dx.doi.org/10.1038/srep18412,PMC4683447,26678425,CC BY,"The upstream pseudoknots domain (UPD) of Tobacco mosaic virus (TMV) is located at the 3′-untranslated region (UTR). It plays an important role in virus replication and translation. To determine the importance of UPD and 3′-UTR, and the effects of introduced RNA elements in TMV 3′-UTR, a series of TMV mutants with internal poly(A) tract upstream of UPD was constructed for structural analysis by selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE). TMV(24A+UPD) and TMV(42A+UPD) formed a similar structure as that of TMV 3′-UTR, but TMV(62A+UPD) structures altered by the introduced poly(A) tract. In addition, TMV(24A+UPD) had a higher viral RNAs accumulation than TMV in N. benthamiana protoplasts, and induced lethal symptoms in the infected plants. TMV(62A+UPD) showed a drastically reduced accumulation, its coat protein was undetectable in protoplasts, and the inoculated plants remained symptomless. This study analyzed the structures of 3′-UTR of TMV and found that the longer poly(A) tract introduced upstream of UPD reduced viral RNAs accumulation and induced milder symptoms in N. benthamiana. In conclusion, different lengths of the internal poly(A) tract introduced into the TMV 3′UTR lead to structural variations that affect virus accumulation and symptom expression.",2015 Dec 18,"['Guo, Song', 'Kierzek, Elzbieta', 'Chen, Gang', 'Zhou, Yi-Jun', 'Wong, Sek-Man']",Sci Rep,,,False
405b2a0699c55c52df71d3a52c454486e2f3ad1c,PMC,"Continued high incidence of children with severe influenza A(H1N1)pdm09 admitted to paediatric intensive care units in Germany during the first three post-pandemic influenza seasons, 2010/11–2012/13",http://dx.doi.org/10.1186/s12879-015-1293-1,PMC4683816,26678835,CC BY,"BACKGROUND: Previous influenza surveillance at paediatric intensive care units (PICUs) in Germany indicated increased incidence of PICU admissions for the pandemic influenza subtype A(H1N1)pdm09. We investigated incidence and clinical characteristics of influenza in children admitted to PICUs during the first three post-pandemic influenza seasons, using active screening. METHODS: We conducted a prospective surveillance study in 24 PICUs in Bavaria (Germany) from October 2010 to September 2013. Influenza cases among children between 1 month and 16 years of age admitted to these PICUs with acute respiratory infection were confirmed by PCR analysis of respiratory secretions. RESULTS: A total of 24/7/20 influenza-associated PICU admissions were recorded in the post-pandemic seasons 1/2/3; incidence estimates per 100,000 children were 1.72/0.76/1.80, respectively. Of all 51 patients, 80 % had influenza A, including 65 % with A(H1N1)pdm09. Influenza A(H1N1)pdm09 was almost absent in season 2 (incidence 0.11), but dominated PICU admissions in seasons 1 (incidence 1.35) and 3 (incidence 1.17). Clinical data was available for 47 influenza patients; median age was 4.8 years (IQR 1.6–11.0). The most frequent diagnoses were influenza-associated pneumonia (62 %), bronchitis/bronchiolitis (32 %), secondary bacterial pneumonia (26 %), and ARDS (21 %). Thirty-six patients (77 %) had underlying medical conditions. Median duration of PICU stay was 3 days (IQR 1–11). Forty-seven per cent of patients received mechanical ventilation, and one patient (2 %) extracorporeal membrane oxygenation; 19 % were treated with oseltamivir. Five children (11 %) had pulmonary sequelae. Five children (11 %) died; all had underlying chronic conditions and were infected with A(H1N1)pdm09. In season 3, patients with A(H1N1)pdm09 were younger than in season 1 (p = 0.020), were diagnosed more often with bronchitis/bronchiolitis (p = 0.004), and were admitted to a PICU later after the onset of influenza symptoms (p = 0.041). CONCLUSIONS: Active screening showed a continued high incidence of A(H1N1)pdm09-associated PICU admissions in the post-pandemic seasons 1 and 3, and indicated possible underestimation of incidence in previous German studies. The age shift of severe A(H1N1)pdm09 towards younger children may be explained by increasing immunity in the older paediatric population. The high proportion of patients with underlying chronic conditions indicates the importance of consistent implementation of the current influenza vaccination recommendations for risk groups in Germany.",2015 Dec 18,"['Streng, Andrea', 'Prifert, Christiane', 'Weissbrich, Benedikt', 'Liese, Johannes G.', None]",BMC Infect Dis,,,True
eb5417b7729ff5548e5b9ddcb837fa52efc586f8,PMC,In silico target fishing and pharmacological profiling for the isoquinoline alkaloids of Macleayacordata (Bo Luo Hui),http://dx.doi.org/10.1186/s13020-015-0067-4,PMC4683977,26691584,CC BY,"BACKGROUND: Some isoquinoline alkaloids from Macleaya cordata (Willd). R. Br. (Bo Luo Hui) exhibited antibacterial, antiparasitic, antitumor, and analgesic effects. The targets of these isoquinoline alkaloids are undefined. This study aims to investigate the compound–target interaction network and potential pharmacological actions of isoquinoline alkaloids of M. cordata by reverse pharmacophore database screening. METHODS: The targets of 26 isoquinoline alkaloids identified from M. cordata were predicted by a pharmacophore-based target fishing approach. Discovery Studio 3.5 and two pharmacophore databases (PharmaDB and HypoDB) were employed for the target profiling. A compound–target interaction network of M. cordata was constructed and analyzed by Cytoscape 3.0. RESULTS: Thirteen of the 65 predicted targets identified by PharmaDB were confirmed as targets by HypoDB screening. The targets in the interaction network of M. cordata were involved in cancer (31 targets), microorganisms (12 targets), neurodegeneration (10 targets), inflammation and autoimmunity (8 targets), parasitosis (5 targets), injury (4 targets), and pain (3 targets). Dihydrochelerythrine (C6) was found to hit 23 fitting targets. Macrophage migration inhibitory factor (MIF) hits 15 alkaloids (C1–2, C11–16, C19–25) was the most promising target related to cancer. CONCLUSION: Through in silico target fishing, the anticancer, anti-inflammatory, and analgesic effects of M. cordata were the most significant among many possible activities. The possible anticancer effects were mainly contributed by the isoquinoline alkaloids as active components.",2015 Dec 17,"['Lei, Qifang', 'Liu, Haibo', 'Peng, Yong', 'Xiao, Peigen']",Chin Med,,,True
25397e5a50461221e9a0706147a6b6e3ad449ac9,PMC,MERS-CoV geography and ecology in the Middle East: analyses of reported camel exposures and a preliminary risk map,http://dx.doi.org/10.1186/s13104-015-1789-1,PMC4684610,26683322,CC BY,"BACKGROUND: Middle Eastern respiratory syndrome coronavirus (MERS-CoV) has spread rapidly across much of the Middle East, but no quantitative mapping of transmission risk has been developed to date. Moreover, details of the transmission cycle of the virus remain unclear, particularly regarding the role of camels as a reservoir host for human infections. METHODS: We present a first analysis of the environmental circumstances under which MERS-CoV cases have occurred in the Middle East, covering all case occurrences through May 2015, using ecological niche modeling approaches to map transmission risk. We compare the environmental breadth of conditions under which cases have reported camel contacts with that of the broader population of all cases, to assess whether camel-associated cases occur under a more restricted set of environmental circumstances. RESULTS: We documented geographic and environmental distributions of MERS-CoV cases across the Middle East, and offer preliminary mapping of transmission risk. We confirm the idea that climatic dimensions of camel-associated cases are more constrained and less variable than the broader suite of case occurrences; hence, camel exposure may be a key limiting element in MERS-CoV transmission. CONCLUSION: This study offers a first detailed geographic and environmental analysis of MERS-CoV distributions across the Middle East. Results indicated that camel-exposed cases occur under a narrower suite of environmental conditions than non-camel-exposed cases, suggesting perhaps a key role for camels in the transmission of the disease, and perhaps a narrower area of risk for ‘primary,’ camel-derived cases of MERS.",2015 Dec 18,"['Reeves, Tarian', 'Samy, Abdallah M.', 'Peterson, A. Townsend']",BMC Res Notes,,,True
f28c1e92be3354c2df1cb282177ef962c3b5c9c6,PMC,Strategies for Pharmacological Organoprotection during Extracorporeal Circulation Targeting Ischemia-Reperfusion Injury,http://dx.doi.org/10.3389/fphar.2015.00296,PMC4686733,26733868,CC BY,"Surgical correction of congenital cardiac malformations or aortocoronary bypass surgery in many cases implies the use of cardiopulmonary-bypass (CPB). However, a possible negative impact of CPB on internal organs such as brain, kidney, lung and liver cannot be neglected. In general, CPB initiates a systemic inflammatory response (SIRS) which is presumably caused by contact of blood components with the surface of CPB tubing. Moreover, during CPB the heart typically undergoes a period of cold ischemia, and the other peripheral organs a global low flow hypoperfusion. As a result, a plethora of pro-inflammatory mediators and cytokines is released activating different biochemical pathways, which finally may result in the occurrence of microthrombosis, microemboli, in depletion of coagulation factors and haemorrhagic diathesis besides typical ischemia-reperfusion injuries. In our review we will focus on possible pharmacological interventions in patients to decrease negative effects of CPB and to improve post-operative outcome with regard to heart and other organs like brain, kidney, or lung.",2015 Dec 22,"['Salameh, Aida', 'Dhein, Stefan']",Front Pharmacol,,,True
575faff450d20d0f359d000ebc8b66b638094613,PMC,Gliopathy of Demyelinating and Non-Demyelinating Strains of Mouse Hepatitis Virus,http://dx.doi.org/10.3389/fncel.2015.00488,PMC4686739,26733813,CC BY,"Demyelination in the central nervous system induced by neurovirulent strains of Mouse Hepatitis Virus (MHV) is mediated by the viral spike glycoprotein, but it is not clear whether the mechanism of this disease pathology involves direct viral infection of oligodendrocytes. Detailed studies of glial cell tropism of MHV are presented, demonstrating that direct MHV infection of oligodendrocytes differs between demyelinating (RSA59) and non-demyelinating (RSMHV2) viral strains both in vitro and in vivo. Our results indicate that direct injury of mature oligodendrocytes is an important mechanism of virus-induced demyelination. In vivo, RSA59 infection was identified in spinal cord gray and white matter, but infected oligodendrocytes were restricted to white matter. In contrast, RSMHV2 infection was restricted to gray matter neurons and was not localized to oligodendrocytes. In vitro, RSA59 can infect both oligodendrocyte precursors and differentiated oligodendrocytes, whereas RSMHV2 can infect oligodendrocyte precursors but not differentiated oligodendrocytes. Viral spreading through axonal means to white matter and release of the demyelinating strain MHV at the nerve end is critical for oligodendrocytes infection and subsequent demyelination. Understanding the mechanisms by which known viruses effect demyelination in this animal model has important therapeutic implications in the treatment of human demyelinating disease.",2015 Dec 22,"['Kenyon, Lawrence C.', 'Biswas, Kaushiki', 'Shindler, Kenneth S.', 'Nabar, Manasi', 'Stout, Marjorie', 'Hingley, Susan T.', 'Grinspan, Judith B.', 'Das Sarma, Jayasri']",Front Cell Neurosci,,,True
27ea5838cb5cf114ddeecd9972be98813834ef9c,PMC,Risk Distribution of Human Infections with Avian Influenza H7N9 and H5N1 virus in China,http://dx.doi.org/10.1038/srep18610,PMC4686887,26691585,CC BY,"It has been documented that the epidemiological characteristics of human infections with H7N9 differ significantly between H5N1. However, potential factors that may explain the different spatial distributions remain unexplored. We use boosted regression tree (BRT) models to explore the association of agro-ecological, environmental and meteorological variables with the occurrence of human cases of H7N9 and H5N1, and map the probabilities of occurrence of human cases. Live poultry markets, density of human, coverage of built-up land, relative humidity and precipitation were significant predictors for both. In addition, density of poultry, coverage of shrub and temperature played important roles for human H7N9 infection, whereas human H5N1 infection was associated with coverage of forest and water body. Based on the risks and distribution of ecological characteristics which may facilitate the circulation of the two viruses, we found Yangtze River Delta and Pearl River Delta, along with a few spots on the southeast coastline, to be the high risk areas for H7N9 and H5N1. Additional, H5N1 risk spots were identified in eastern Sichuan and southern Yunnan Provinces. Surveillance of the two viruses needs to be enhanced in these high risk areas to reduce the risk of future epidemics of avian influenza in China.",2015 Dec 22,"['Li, Xin-Lou', 'Yang, Yang', 'Sun, Ye', 'Chen, Wan-Jun', 'Sun, Ruo-Xi', 'Liu, Kun', 'Ma, Mai-Juan', 'Liang, Song', 'Yao, Hong-Wu', 'Gray, Gregory C.', 'Fang, Li-Qun', 'Cao, Wu-Chun']",Sci Rep,,,True
67466fd44aa1843c57174386e917578f0d83d71a,PMC,Modeling the Transmission of Middle East Respirator Syndrome Corona Virus in the Republic of Korea,http://dx.doi.org/10.1371/journal.pone.0144778,PMC4686901,26690750,CC BY,"The 2015 epidemic of Middle East respiratory syndrome (MERS) in the Republic of Korea has been the largest outbreak outside Middle East. This epidemic had caused 185 laboratory-confirmed cases and 36 deaths in the Republic of Korea until September 2, 2015, which attracted public’s attention. Based on the detailed data of patients released by World Health Organization (WHO) and actual propagation of the epidemic, we construct two dynamical models to simulate the propagation processes from May 20 to June 8 and from June 9 to July 10, 2015, respectively and find that the basic reproduction number R (0) reaches up to 4.422. The numerical analysis shows that the reasons of the outbreak spread quickly are lack of self-protection sense and targeted control measures. Through partial correction analysis, the parameters β (1) and γ have strong correlations with R (0), i.e., the infectivity and proportion of the asymptomatic infected cases have much influence on the spread of disease. By sensitivity analysis, strengthening self-protection ability of susceptible and quickly isolating or monitoring close contacts are effective measures to control the disease.",2015 Dec 21,"['Xia, Zhi-Qiang', 'Zhang, Juan', 'Xue, Ya-Kui', 'Sun, Gui-Quan', 'Jin, Zhen']",PLoS One,,,True
40640676ca5aecdde3a40feb137cc3049c14faef,PMC,Modeling the Transmission of Middle East Respirator Syndrome Corona Virus in the Republic of Korea,http://dx.doi.org/10.1371/journal.pone.0144778,PMC4686901,26690750,CC BY,"The 2015 epidemic of Middle East respiratory syndrome (MERS) in the Republic of Korea has been the largest outbreak outside Middle East. This epidemic had caused 185 laboratory-confirmed cases and 36 deaths in the Republic of Korea until September 2, 2015, which attracted public’s attention. Based on the detailed data of patients released by World Health Organization (WHO) and actual propagation of the epidemic, we construct two dynamical models to simulate the propagation processes from May 20 to June 8 and from June 9 to July 10, 2015, respectively and find that the basic reproduction number R (0) reaches up to 4.422. The numerical analysis shows that the reasons of the outbreak spread quickly are lack of self-protection sense and targeted control measures. Through partial correction analysis, the parameters β (1) and γ have strong correlations with R (0), i.e., the infectivity and proportion of the asymptomatic infected cases have much influence on the spread of disease. By sensitivity analysis, strengthening self-protection ability of susceptible and quickly isolating or monitoring close contacts are effective measures to control the disease.",2015 Dec 21,"['Xia, Zhi-Qiang', 'Zhang, Juan', 'Xue, Ya-Kui', 'Sun, Gui-Quan', 'Jin, Zhen']",PLoS One,,,True
abd80dcf360dafb7c921416daedc2021908c3503,PMC,Coronaviruses: emerging and re-emerging pathogens in humans and animals,http://dx.doi.org/10.1186/s12985-015-0432-z,PMC4687117,26690088,CC BY,"The severe acute respiratory syndrome coronavirus (SARS-CoV) and recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) epidemics have proven the ability of coronaviruses to cross species barrier and emerge rapidly in humans. Other coronaviruses such as porcine epidemic diarrhea virus (PEDV) are also known to cause major disease epidemics in animals wiith huge economic loss. This special issue in Virology Journal aims to highlight the advances and key discoveries in the animal origin, viral evolution, epidemiology, diagnostics and pathogenesis of the emerging and re-emerging coronaviruses in both humans and animals.",2015 Dec 22,"['Lau, Susanna K. P.', 'Chan, Jasper F. W.']",Virol J,,,True
a63f9b0555e4ec19bb5a38d4e4f282ed9bbb8612,PMC,Non-coding yet non-trivial: a review on the computational genomics of lincRNAs,http://dx.doi.org/10.1186/s13040-015-0075-z,PMC4687140,26697116,CC BY,"Long intergenic non-coding RNAs (lincRNAs) represent one of the most mysterious RNA species encoded by the human genome. Thanks to next generation sequencing (NGS) technology and its applications, we have recently witnessed a surge in non-coding RNA research, including lincRNA research. Here, we summarize the recent advancement in genomics studies of lincRNAs. We review the emerging characteristics of lincRNAs, the experimental and computational approaches to identify lincRNAs, their known mechanisms of regulation, the computational methods and resources for lincRNA functional predictions, and discuss the challenges to understanding lincRNA comprehensively.",2015 Dec 22,"['Ching, Travers', 'Masaki, Jayson', 'Weirather, Jason', 'Garmire, Lana X.']",BioData Min,,,True
12f712c348c26e092759d804778defe2d2d4af6f,PMC,Middle East respiratory syndrome coronavirus infection: virus-host cell interactions and implications on pathogenesis,http://dx.doi.org/10.1186/s12985-015-0446-6,PMC4687146,26690369,CC BY,"Middle-East Respiratory Syndrome coronavirus (MERS-CoV) was identified to cause severe respiratory infection in humans since 2012. The continuing MERS epidemic with a case-fatality of more than 30 % poses a major threat to public health worldwide. Currently, the pathogenesis of human MERS-CoV infection remains poorly understood. We reviewed experimental findings from human primary cells and ex vivo human lung tissues, as well as those from animal studies, so as to understand the pathogenesis and high case-fatality of MERS. Human respiratory epithelial cells are highly susceptible to MERS-CoV and can support productive viral replication. However, the induction of antiviral cytokines and proinflammatory cytokines/chemokines are substantially dampened in the infected epithelial cells, due to the antagonistic mechanisms evolved by the virus. MERS-CoV can readily infect and robustly replicate in human macrophages and dendritic cells, triggering the aberrant production of proinflammatory cytokines/chemokines. MERS-CoV can also effectively infect human primary T cells and induce massive apoptosis in these cells. Although data from clinical, in vitro and ex vivo studies suggested the potential for virus dissemination, extrapulmonary involvement in MERS patients has not been ascertained due to the lack of autopsy study. In MERS-CoV permissive animal models, although viral RNA can be detected from multiple organs of the affected animals, the brain of human DPP4-transgenic mouse was the only extrapulmonary organ from which the infectious virus can be recovered. More research findings on the pathogenesis of MERS and the tissue tropisms of MERS-CoV may help to improve the treatment and infection control of MERS.",2015 Dec 22,"['Zhou, Jie', 'Chu, Hin', 'Chan, Jasper Fuk-Woo', 'Yuen, Kwok-Yung']",Virol J,,,True
a672930b5dc73b6002ca4a697e2109b130dee042,PMC,Porcine epidemic diarrhea virus: An emerging and re-emerging epizootic swine virus,http://dx.doi.org/10.1186/s12985-015-0421-2,PMC4687282,26689811,CC BY,"The enteric disease of swine recognized in the early 1970s in Europe was initially described as “epidemic viral diarrhea” and is now termed “porcine epidemic diarrhea (PED)”. The coronavirus referred to as PED virus (PEDV) was determined to be the etiologic agent of this disease in the late 1970s. Since then the disease has been reported in Europe and Asia, but the most severe outbreaks have occurred predominantly in Asian swine-producing countries. Most recently, PED first emerged in early 2013 in the United States that caused high morbidity and mortality associated with PED, remarkably affecting US pig production, and spread further to Canada and Mexico. Soon thereafter, large-scale PED epidemics recurred through the pork industry in South Korea, Japan, and Taiwan. These recent outbreaks and global re-emergence of PED require urgent attention and deeper understanding of PEDV biology and pathogenic mechanisms. This paper highlights the current knowledge of molecular epidemiology, diagnosis, and pathogenesis of PEDV, as well as prevention and control measures against PEDV infection. More information about the virus and the disease is still necessary for the development of effective vaccines and control strategies. It is hoped that this review will stimulate further basic and applied studies and encourage collaboration among producers, researchers, and swine veterinarians to provide answers that improve our understanding of PEDV and PED in an effort to eliminate this economically significant viral disease, which emerged or re-emerged worldwide.",2015 Dec 22,"Lee, Changhee",Virol J,,,True
f1570e2dfd60e3bc423fede19c89171ac06da885,PMC,Retroviral DNA—the silent winner: blood transfusion containing latent feline leukemia provirus causes infection and disease in naïve recipient cats,http://dx.doi.org/10.1186/s12977-015-0231-z,PMC4687292,26689419,CC BY,"BACKGROUND: The feline leukemia virus (FeLV) is a gamma-retrovirus of domestic cats that was discovered half a century ago. Cats that are infected with FeLV may develop a progressive infection resulting in persistent viremia, immunodeficiency, tumors, anemia and death. A significant number of cats mount a protective immune response that suppresses viremia; these cats develop a regressive infection characterized by the absence of viral replication and the presence of low levels of proviral DNA. The biological importance of these latter provirus carriers is largely unknown. RESULTS: Here, we demonstrate that ten cats that received a transfusion of blood from aviremic provirus carriers developed active FeLV infections, some with a progressive outcome and the development of fatal FeLV-associated disease. The infection outcome, disease spectrum and evolution into FeLV-C in one cat mirrored those of natural infection. Two cats developed persistent antigenemia; six cats were transiently antigenemic. Reactivation of infection occurred in some cats. One recipient developed non-regenerative anemia associated with FeLV-C, and four others developed a T-cell lymphoma, one with secondary lymphoblastic leukemia. Five of the ten recipient cats received provirus-positive aviremic blood, whereas the other five received provirus- and viral RNA-positive but aviremic blood. Notably, the cats that received blood containing only proviral DNA exhibited a later onset but graver outcome of FeLV infection than the cats that were transfused with blood containing proviral DNA and viral RNA. Leukocyte counts and cytokine analyses indicated that the immune system of the latter cats reacted quicker and more efficiently. CONCLUSIONS: Our results underline the biological and epidemiological relevance of FeLV provirus carriers and the risk of inadvertent FeLV transmission via blood transfusion and demonstrate the replication capacity of proviral DNA if uncontrolled by the immune system. Our results have implications not only for veterinary medicine, such as the requirement for testing blood donors and blood products for FeLV provirus by sensitive polymerase chain reaction, but are also of general interest by revealing the importance of latent retroviral DNA in infected hosts. When aiming to eliminate a retroviral infection from a population, provirus carriers must be considered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-015-0231-z) contains supplementary material, which is available to authorized users.",2015 Dec 21,"['Nesina, Stefanie', 'Katrin Helfer-Hungerbuehler, A.', 'Riond, Barbara', 'Boretti, Felicitas S.', 'Willi, Barbara', 'Meli, Marina L.', 'Grest, Paula', 'Hofmann-Lehmann, Regina']",Retrovirology,,,True
8a14b75626a9cad7cac350437b7af5e0e4bd5127,PMC,Bat origin of human coronaviruses,http://dx.doi.org/10.1186/s12985-015-0422-1,PMC4687304,26689940,CC BY,"Bats have been recognized as the natural reservoirs of a large variety of viruses. Special attention has been paid to bat coronaviruses as the two emerging coronaviruses which have caused unexpected human disease outbreaks in the 21st century, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), are suggested to be originated from bats. Various species of horseshoe bats in China have been found to harbor genetically diverse SARS-like coronaviruses. Some strains are highly similar to SARS-CoV even in the spike protein and are able to use the same receptor as SARS-CoV for cell entry. On the other hand, diverse coronaviruses phylogenetically related to MERS-CoV have been discovered worldwide in a wide range of bat species, some of which can be classified to the same coronavirus species as MERS-CoV. Coronaviruses genetically related to human coronavirus 229E and NL63 have been detected in bats as well. Moreover, intermediate hosts are believed to play an important role in the transmission and emergence of these coronaviruses from bats to humans. Understanding the bat origin of human coronaviruses is helpful for the prediction and prevention of another pandemic emergence in the future.",2015 Dec 22,"['Hu, Ben', 'Ge, Xingyi', 'Wang, Lin-Fa', 'Shi, Zhengli']",Virol J,,,True
f6fcf1a99cbd073c5821d1c4ffa3f2c6daf8ae29,PMC,"MERS coronavirus: diagnostics, epidemiology and transmission",http://dx.doi.org/10.1186/s12985-015-0439-5,PMC4687373,26695637,CC BY,"The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia (KSA). Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels (DC). MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract (LRT) disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute respiratory syndrome (SARS), another sometimes- fatal zoonotic coronavirus disease that has since disappeared, MERS progresses more rapidly to respiratory failure and acute kidney injury (it also has an affinity for growth in kidney cells under laboratory conditions), is more frequently reported in patients with underlying disease and is more often fatal. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20 % of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Sero-surveys have found widespread evidence of past infection in adult camels and limited past exposure among humans. Sensitive, validated reverse transcriptase real-time polymerase chain reaction (RT-rtPCR)-based diagnostics have been available almost from the start of the emergence of MERS. While the basic virology of MERS-CoV has advanced over the past three years, understanding of the interplay between camel, environment, and human remains limited. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0439-5) contains supplementary material, which is available to authorized users.",2015 Dec 22,"['Mackay, Ian M.', 'Arden, Katherine E.']",Virol J,,,True
6fdb54d00b9abc340c37abe6fe840458a8eab54b,PMC,First case of Propionibacterium acnes urinary tract infection in a dog,http://dx.doi.org/10.1186/s12917-015-0620-5,PMC4687383,26690238,CC BY,"BACKGROUND: Propionibacterium acnes has been rarely isolated as a commensal from dogs, but there is little evidence of pathogenicity. Urinary tract infections are common in dogs and are typically caused by various commensal bacteria. Here we present the first case report of a urinary tract infection caused by P. acnes. CASE PRESENTATION: A 6-year-old female Japanese Shiba Inu was hospitalized for polyuria, polydipsia, and severe hematuria. At admission, blood tests revealed leukocytosis, slight anemia, decreased albumin, and slightly elevated blood urea nitrogen. Computerized tomography showed gas accumulation on the inner side of the bladder wall. Urinalysis revealed proteinuria and bilirubinuria without glycosuria. The urine sediment contained large numbers of erythrocytes and leukocytes. Additionally, rod-shaped bacteria were detected by Diff-Quik staining. Enrofloxacin and metronidazole were administered empirically; however, the renal function declined sharply and the patient died 2 days later. Bacteriological examination revealed that the causative agent was Propionibacterium acnes, which was identified as sequence type 53 via multilocus sequence typing. This isolate showed high susceptibility to ampicillin, amoxicillin/clavulanic acid, cefoxitin, imipenem, clindamycin, tetracycline, chloramphenicol, and enrofloxacin, but was resistant to metronidazole. CONCLUSION: To the best of our knowledge, this is the first case report of a dog with urinary tract infection caused by P. acnes.",2015 Dec 21,"['Harada, Kazuki', 'Shimizu, Takae', 'Tsuka, Takeshi', 'Imagawa, Tomohiro', 'Takeuchi, Takashi']",BMC Vet Res,,,True
60cfb43ca9b8d54f5b8cb4ab264d8d628c7c227b,PMC,Early occurrence of influenza A epidemics coincided with changes in occurrence of other respiratory virus infections,http://dx.doi.org/10.1111/irv.12348,PMC4687500,26369646,CC BY,"BACKGROUND: Viral interaction in which outbreaks of influenza and other common respiratory viruses might affect each other has been postulated by several short studies. Regarding longer time periods, influenza epidemics occasionally occur very early in the season, as during the 2009 pandemic. Whether early occurrence of influenza epidemics impacts outbreaks of other common seasonal viruses is not clear. OBJECTIVES: We investigated whether early occurrence of influenza outbreaks coincides with shifts in the occurrence of other common viruses, including both respiratory and non‐respiratory viruses. METHODS: We investigated time trends of and the correlation between positive laboratory diagnoses of eight common viruses in the Netherlands over a 10‐year time period (2003–2012): influenza viruses types A and B, respiratory syncytial virus (RSV), rhinovirus, coronavirus, norovirus, enterovirus, and rotavirus. We compared trends in viruses between early and late influenza seasons. RESULTS: Between 2003 and 2012, influenza B, RSV, and coronavirus showed shifts in their occurrence when influenza A epidemics occurred earlier than usual (before week 1). Although shifts were not always consistently of the same type, when influenza type A hit early, RSV outbreaks tended to be delayed, coronavirus outbreaks tended to be intensified, and influenza virus type B tended not to occur at all. Occurrence of rhinovirus, norovirus, rotavirus, and enterovirus did not change. CONCLUSION: When influenza A epidemics occured early, timing of the epidemics of several respiratory winter viruses usually occurring close in time to influenza A was affected, while trends in rhinoviruses (occurring in autumn) and trends in enteral viruses were not.",2016 Jan 11,"['van Asten, Liselotte', 'Bijkerk, Paul', 'Fanoy, Ewout', 'van Ginkel, Annemarijn', 'Suijkerbuijk, Anita', 'van der Hoek, Wim', 'Meijer, Adam', 'Vennema, Harry']",Influenza Other Respir Viruses,,,True
59d9705d1665532f12f9014317352297b8a834e3,PMC,Direct costs of acute respiratory infections in a pediatric long‐term care facility,http://dx.doi.org/10.1111/irv.12350,PMC4687501,26425787,CC BY,"Acute respiratory tract infections (ARI) are a major burden in pediatric long‐term care. We analyzed the financial impact of ARI in 2012–2013. Costs associated with ARI during the respiratory viral season were ten times greater than during the non‐respiratory viral season, $31 224 and $3242 per 1000 patient‐days, respectively (P < 0·001). ARI are burdensome for pediatric long‐term care facilities not only because of the associated morbidity and mortality, but also due to the great financial costs of prevention.",2016 Jan 11,"['Murray, Meghan T.', 'Heitkemper, Elizabeth', 'Jackson, Olivia', 'Neu, Natalie', 'Stone, Patricia', 'Cohen, Bevin', 'Saiman, Lisa', 'Hutcheon, Gordon', 'Larson, Elaine L.']",Influenza Other Respir Viruses,,,True
1efd8ee0124faf388961ff309a10ca2cfba5268c,PMC,Etiology and Factors Associated with Pneumonia in Children under 5 Years of Age in Mali: A Prospective Case-Control Study,http://dx.doi.org/10.1371/journal.pone.0145447,PMC4687909,26696249,CC BY,"BACKGROUND: There are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children <5 years of age in Mali. METHODS: A prospective hospital-based case-control study was implemented in the Pediatric department of Gabriel Touré University Hospital at Bamako, Mali, between July 2011-December 2012. Cases were children with radiologically-confirmed pneumonia; Controls were hospitalized children without respiratory features, matched for age and period. Respiratory specimens, were collected to identify 19 viruses and 5 bacteria. Whole blood was collected from cases only. Factors associated with pneumonia were assessed by multivariate logistic regression. RESULTS: Overall, 118 cases and 98 controls were analyzed; 44.1% were female, median age was 11 months. Among pneumonia cases, 30.5% were hypoxemic at admission, mortality was 4.2%. Pneumonia cases differed from the controls regarding clinical signs and symptoms but not in terms of past medical history. Multivariate analysis of nasal swab findings disclosed that S. pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6–7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0–151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3–23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0–112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. Distribution of S. pneumoniae and RSV differed by season with higher rates of S. pneumoniae in January-June and of RSV in July-September. Pneumococcal serotypes 1 and 5 were more frequent in pneumonia cases than in the controls (P = 0.009, and P = 0.04, respectively). CONCLUSIONS: In this non-PCV population from Mali, pneumonia in children was mainly attributed to S. pneumoniae, RSV, human metapneumovirus, and influenza A virus. Increased pneumococcal conjugate vaccine coverage in children could significantly reduce the burden of pneumonia in sub-Saharan African countries.",2015 Dec 22,"['Bénet, Thomas', 'Sylla, Mariam', 'Messaoudi, Mélina', 'Sánchez Picot, Valentina', 'Telles, Jean-Noël', 'Diakite, Abdoul-Aziz', 'Komurian-Pradel, Florence', 'Endtz, Hubert', 'Diallo, Souleymane', 'Paranhos-Baccalà, Gláucia', 'Vanhems, Philippe']",PLoS One,,,True
db30c72b055266cbd06bb14d7f570f91d8e84e6e,PMC,Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus,http://dx.doi.org/10.1371/journal.pone.0145561,PMC4689477,26701103,CC BY,"The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4), the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection.",2015 Dec 23,"['Zhao, Guangyu', 'Jiang, Yuting', 'Qiu, Hongjie', 'Gao, Tongtong', 'Zeng, Yang', 'Guo, Yan', 'Yu, Hong', 'Li, Junfeng', 'Kou, Zhihua', 'Du, Lanying', 'Tan, Wenjie', 'Jiang, Shibo', 'Sun, Shihui', 'Zhou, Yusen']",PLoS One,,,True
473207b36a728a21e7545bcde584d8618f714552,PMC,2015 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) nosocomial outbreak in South Korea: insights from modeling,http://dx.doi.org/10.7717/peerj.1505,PMC4690341,26713252,CC BY,"Background. Since the emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012, more than 1,300 laboratory confirmed cases of MERS-CoV infections have been reported in Asia, North Africa, and Europe by July 2015. The recent MERS-CoV nosocomial outbreak in South Korea quickly became the second largest such outbreak with 186 total cases and 36 deaths in a little more than one month, second only to Saudi Arabia in country-specific number of reported cases. Methods. We use a simple mathematical model, the Richards model, to trace the temporal course of the South Korea MERS-CoV outbreak. We pinpoint its outbreak turning point and its transmissibility via basic reproduction number R(0) in order to ascertain the occurrence of this nosocomial outbreak and how it was quickly brought under control. Results. The estimated outbreak turning point of t(i) = 23.3 days (95% CI [22.6–24.0]), or 23–24 days after the onset date of the index case on May 11, pinpoints June 3–4 as the time of the turning point or the peak incidence for this outbreak by onset date. R(0) is estimated to range between 7.0 and 19.3. Discussion and Conclusion. The turning point of the South Korea MERS-CoV outbreak occurred around May 27–29, when control measures were quickly implemented after laboratory confirmation of the first cluster of nosocomial infections by the index patient. Furthermore, transmissibility of MERS-CoV in the South Korea outbreak was significantly higher than those reported from past MERS-CoV outbreaks in the Middle East, which is attributable to the nosocomial nature of this outbreak. Our estimate of R(0) for the South Korea MERS-CoV nosocomial outbreak further highlights the importance and the risk involved in cluster infections and superspreading events in crowded settings such as hospitals. Similar to the 2003 SARS epidemic, outbreaks of infectious diseases with low community transmissibility like MERS-CoV could still occur initially with large clusters of nosocomial infections, but can be quickly and effectively controlled with timely intervention measures.",2015 Dec 17,"Hsieh, Ying-Hen",PeerJ,,,True
b2d2050a4b62e13a5c78e23190f61a7895ca33e2,PMC,Analysis of synonymous codon usage patterns in sixty-four different bivalve species,http://dx.doi.org/10.7717/peerj.1520,PMC4690358,26713259,CC BY,"Synonymous codon usage bias (CUB) is a defined as the non-random usage of codons encoding the same amino acid across different genomes. This phenomenon is common to all organisms and the real weight of the many factors involved in its shaping still remains to be fully determined. So far, relatively little attention has been put in the analysis of CUB in bivalve mollusks due to the limited genomic data available. Taking advantage of the massive sequence data generated from next generation sequencing projects, we explored codon preferences in 64 different species pertaining to the six major evolutionary lineages in Bivalvia. We detected remarkable differences across species, which are only partially dependent on phylogeny. While the intensity of CUB is mild in most organisms, a heterogeneous group of species (including Arcida and Mytilida, among the others) display higher bias and a strong preference for AT-ending codons. We show that the relative strength and direction of mutational bias, selection for translational efficiency and for translational accuracy contribute to the establishment of synonymous codon usage in bivalves. Although many aspects underlying bivalve CUB still remain obscure, we provide for the first time an overview of this phenomenon in this large, commercially and environmentally important, class of marine invertebrates.",2015 Dec 14,"['Gerdol, Marco', 'De Moro, Gianluca', 'Venier, Paola', 'Pallavicini, Alberto']",PeerJ,,,True
1392d02729b5e2f1a63ff3ff259e10a8c45e5a55,PMC,The effectiveness of a shared conference experience in improving undergraduate medical and nursing students’ attitudes towards inter-professional education in an Asian country: a before and after study,http://dx.doi.org/10.1186/s12909-015-0509-9,PMC4690434,26698562,CC BY,"BACKGROUND: In recent years, increasing emphasis has been placed on the importance of collaboration within multi-disciplinary healthcare teams, so as to facilitate holistic patient care and thus allow improved treatment outcomes. There is hence an urgent need to educate healthcare undergraduates early in their professional careers on the importance of and complexities involved in cooperating with counterparts from other allied healthcare professions. In conjunction with this, a milestone student-led conference for undergraduate students, the 9th Student Medical-Nursing Education Conference (SMEC), was organised in 2013 to provide a unique opportunity for shared learning among the entire cohort of undergraduate medical and nursing students in Singapore matriculating in that year. METHODS: This study evaluated the effectiveness of the 9th SMEC 2013 as a shared conference experience in improving the attitudes of undergraduate medical and nursing students in Singapore towards inter-professional education (IPE). A 19-point Readiness for Inter-Professional Learning Scale (RIPLS) questionnaire comprising three subscales was administered to participants both before and after the conference. 352 responses were collected, giving a response rate of 75.1 %. Results were analysed using paired-samples t-tests with statistical significance set at p = 0.05. RESULTS: Improvements in overall scores for both medical and nursing students were reported for all three RIPLS subscales. Examining the RIPLS items individually, significant improvement in scores for both medical and nursing students was obtained in all 19 items. Prior exposure to IPE activities was not a predictor of improvement in IPE attitudes. CONCLUSION: The authors propose that student-led jointly-organised conference experiences are effective in improving healthcare students’ attitudes towards IPE. This study provides valuable insights to facilitate the development of further IPE programs to allow for the rapid and effective promotion of cooperation and collaboration between students across various healthcare disciplines.",2015 Dec 23,"['Chua, Amelia ZE', 'Lo, Daryl YK', 'Ho, Wilbert HH', 'Koh, Yun Qing', 'Lim, Daniel SY', 'Tam, John KC', 'Liaw, Sok Ying', 'Koh, Gerald CH']",BMC Med Educ,,,True
64c59c6ee1a8693c4bc296bf844047426f046e1b,PMC,Activation of the Mitochondrial Apoptotic Signaling Platform during Rubella Virus Infection,http://dx.doi.org/10.3390/v7122928,PMC4690853,26703711,CC BY,"Mitochondria- as well as p53-based signaling pathways are central for the execution of the intrinsic apoptotic cascade. Their contribution to rubella virus (RV)-induced apoptosis was addressed through time-specific evaluation of characteristic parameters such as permeabilization of the mitochondrial membrane and subsequent release of the pro-apoptotic proteins apoptosis-inducing factor (AIF) and cytochrome c from mitochondria. Additionally, expression and localization pattern of p53 and selected members of the multifunctional and stress-inducible cyclophilin family were examined. The application of pifithrin μ as an inhibitor of p53 shuttling to mitochondria reduced RV-induced cell death to an extent similar to that of the broad spectrum caspase inhibitor z-VAD-fmk (benzyloxycarbonyl-V-A-D-(OMe)-fmk). However, RV progeny generation was not altered. This indicates that, despite an increased survival rate of its cellular host, induction of apoptosis neither supports nor restricts RV replication. Moreover, some of the examined apoptotic markers were affected in a strain-specific manner and differed between the cell culture-adapted strains: Therien and the HPV77 vaccine on the one hand, and a clinical isolate on the other. In summary, the results presented indicate that the transcription-independent mitochondrial p53 program contributes to RV-induced apoptosis.",2015 Nov 26,"['Claus, Claudia', 'Manssen, Lena', 'Hübner, Denise', 'Roßmark, Sarah', 'Bothe, Viktoria', 'Petzold, Alice', 'Große, Claudia', 'Reins, Mareen', 'Mankertz, Annette', 'Frey, Teryl K.', 'Liebert, Uwe G.']",Viruses,,,True
d9d2f8f421d0290a8dbf0ec92cbbe1ad2d93a694,PMC,Alphacoronaviruses Detected in French Bats Are Phylogeographically Linked to Coronaviruses of European Bats,http://dx.doi.org/10.3390/v7122937,PMC4690861,26633467,CC BY,"Bats are a reservoir for a diverse range of viruses, including coronaviruses (CoVs). To determine the presence of CoVs in French bats, fecal samples were collected between July and August of 2014 from four bat species in seven different locations around the city of Bourges in France. We present for the first time the presence of alpha-CoVs in French Pipistrellus pipistrellus bat species with an estimated prevalence of 4.2%. Based on the analysis of a fragment of the RNA-dependent RNA polymerase (RdRp) gene, phylogenetic analyses show that alpha-CoVs sequences detected in French bats are closely related to other European bat alpha-CoVs. Phylogeographic analyses of RdRp sequences show that several CoVs strains circulate in European bats: (i) old strains detected that have probably diverged a long time ago and are detected in different bat subspecies; (ii) strains detected in Myotis and Pipistrellus bat species that have more recently diverged. Our findings support previous observations describing the complexity of the detected CoVs in bats worldwide.",2015 Dec 2,"['Goffard, Anne', 'Demanche, Christine', 'Arthur, Laurent', 'Pinçon, Claire', 'Michaux, Johan', 'Dubuisson, Jean']",Viruses,,,True
86effe356ffd602c096c4252ef1775dab6f62e1f,PMC,Viral Infection at High Magnification: 3D Electron Microscopy Methods to Analyze the Architecture of Infected Cells,http://dx.doi.org/10.3390/v7122940,PMC4690864,26633469,CC BY,"As obligate intracellular parasites, viruses need to hijack their cellular hosts and reprogram their machineries in order to replicate their genomes and produce new virions. For the direct visualization of the different steps of a viral life cycle (attachment, entry, replication, assembly and egress) electron microscopy (EM) methods are extremely helpful. While conventional EM has given important information about virus-host cell interactions, the development of three-dimensional EM (3D-EM) approaches provides unprecedented insights into how viruses remodel the intracellular architecture of the host cell. During the last years several 3D-EM methods have been developed. Here we will provide a description of the main approaches and examples of innovative applications.",2015 Dec 3,"['Romero-Brey, Inés', 'Bartenschlager, Ralf']",Viruses,,,True
6c9ce983d25f6c0727c9e4fedc01e84b046673a4,PMC,Molecular Epidemiology of Human Rhinoviruses and Enteroviruses Highlights Their Diversity in Sub-Saharan Africa,http://dx.doi.org/10.3390/v7122948,PMC4690871,26670243,CC BY,"Human rhinoviruses (HRVs) and enteroviruses (HEVs) belong to the Enterovirus genus and are the most frequent cause of infection worldwide, but data on their molecular epidemiology in Africa are scarce. To understand HRV and HEV molecular epidemiology in this setting, we enrolled febrile pediatric patients participating in a large prospective cohort assessing the causes of fever in Tanzanian children. Naso/oropharyngeal swabs were systematically collected and tested by real-time RT-PCR for HRV and HEV. Viruses from positive samples were sequenced and phylogenetic analyses were then applied to highlight the HRV and HEV types as well as recombinant or divergent strains. Thirty-eight percent (378/1005) of the enrolled children harboured an HRV or HEV infection. Although some types were predominant, many distinct types were co-circulating, including a vaccinal poliovirus, HEV-A71 and HEV-D68. Three HRV-A recombinants were identified: HRV-A36/HRV-A67, HRV-A12/HRV-A67 and HRV-A96/HRV-A61. Four divergent HRV strains were also identified: one HRV-B strain and three HRV-C strains. This is the first prospective study focused on HRV and HEV molecular epidemiology in sub-Saharan Africa. This systematic and thorough large screening with careful clinical data management confirms the wide genomic diversity of these viruses, brings new insights about their evolution and provides data about associated symptoms.",2015 Dec 8,"['L’Huillier, Arnaud G.', 'Kaiser, Laurent', 'Petty, Tom J.', 'Kilowoko, Mary', 'Kyungu, Esther', 'Hongoa, Philipina', 'Vieille, Gaël', 'Turin, Lara', 'Genton, Blaise', 'D’Acremont, Valérie', 'Tapparel, Caroline']",Viruses,,,True
37637426a103bf21e7fe97c97de5087707655923,PMC,Molecular Epidemiology of Human Rhinoviruses and Enteroviruses Highlights Their Diversity in Sub-Saharan Africa,http://dx.doi.org/10.3390/v7122948,PMC4690871,26670243,CC BY,"Human rhinoviruses (HRVs) and enteroviruses (HEVs) belong to the Enterovirus genus and are the most frequent cause of infection worldwide, but data on their molecular epidemiology in Africa are scarce. To understand HRV and HEV molecular epidemiology in this setting, we enrolled febrile pediatric patients participating in a large prospective cohort assessing the causes of fever in Tanzanian children. Naso/oropharyngeal swabs were systematically collected and tested by real-time RT-PCR for HRV and HEV. Viruses from positive samples were sequenced and phylogenetic analyses were then applied to highlight the HRV and HEV types as well as recombinant or divergent strains. Thirty-eight percent (378/1005) of the enrolled children harboured an HRV or HEV infection. Although some types were predominant, many distinct types were co-circulating, including a vaccinal poliovirus, HEV-A71 and HEV-D68. Three HRV-A recombinants were identified: HRV-A36/HRV-A67, HRV-A12/HRV-A67 and HRV-A96/HRV-A61. Four divergent HRV strains were also identified: one HRV-B strain and three HRV-C strains. This is the first prospective study focused on HRV and HEV molecular epidemiology in sub-Saharan Africa. This systematic and thorough large screening with careful clinical data management confirms the wide genomic diversity of these viruses, brings new insights about their evolution and provides data about associated symptoms.",2015 Dec 8,"['L’Huillier, Arnaud G.', 'Kaiser, Laurent', 'Petty, Tom J.', 'Kilowoko, Mary', 'Kyungu, Esther', 'Hongoa, Philipina', 'Vieille, Gaël', 'Turin, Lara', 'Genton, Blaise', 'D’Acremont, Valérie', 'Tapparel, Caroline']",Viruses,,,False
277e85da79677586ae01bb02ea6e410ebc97fd29,PMC,Recent Progress towards Novel EV71 Anti-Therapeutics and Vaccines,http://dx.doi.org/10.3390/v7122949,PMC4690872,26670245,CC BY,"Enterovirus 71 (EV71) is a group of viruses that belongs to the Picornaviridae family, which also includes viruses such as polioviruses. EV71, together with coxsackieviruses, is widely known for its association with Hand Foot Mouth Disease (HFMD), which generally affects children age five and below. Besides HFMD, EV71 can also trigger more severe and life-threatening neurological conditions such as encephalitis. Considering the lack of a vaccine and antiviral drug against EV71, together with the increasing spread of these viruses, the development of such drugs and vaccines becomes the top priority in protecting our younger generations. This article, hence, reviews some of the recent progress in the formulations of anti-therapeutics and vaccine generation for EV71, covering (i) inactivated vaccines; (ii) baculovirus-expressed vaccines against EV71; (iii) human intravenous immunoglobulin (IVIg) treatment; and (iv) the use of monoclonal antibody therapy as a prevention and treatment for EV71 infections.",2015 Dec 8,"['Ng, Qingyong', 'He, Fang', 'Kwang, Jimmy']",Viruses,,,True
dd2054667f5f1db92d4649fc420d0d86dc39dcd9,PMC,CDC42 Use in Viral Cell Entry Processes by RNA Viruses,http://dx.doi.org/10.3390/v7122955,PMC4690878,26690467,CC BY,"The cellular actin cytoskeleton presents a barrier that must be overcome by many viruses, and it has become increasingly apparent many viral species have developed a diverse repertoire of mechanisms to hijack cellular actin-regulating signalling pathways as part of their cell entry processes. The Rho family GTPase Cdc42 is appreciated as a key moderator of cellular actin dynamics, and the development of specific Cdc42-inhibiting agents has given us an unprecedented ability to investigate its individual role in signalling pathways. However, investigative use of said agents, and the subsequent characterisation of the role Cdc42 plays in viral entry processes has been lacking. Here, we describe the current literature on the role of Cdc42 in human immunodeficiency virus (HIV)-1 cell entry, which represents the most investigated instance of Cdc42 function in viral cell entry processes, and also review evidence of Cdc42 use in other RNA virus cell entries, demonstrating prime areas for more extensive research using similar techniques.",2015 Dec 10,"['Swaine, Thomas', 'Dittmar, Matthias T.']",Viruses,,,True
e9011bcb647874593aa8c4c7a3010573f82a1558,PMC,Herpesvirus gB: A Finely Tuned Fusion Machine,http://dx.doi.org/10.3390/v7122957,PMC4690880,26690469,CC BY,"Enveloped viruses employ a class of proteins known as fusogens to orchestrate the merger of their surrounding envelope and a target cell membrane. Most fusogens accomplish this task alone, by binding cellular receptors and subsequently catalyzing the membrane fusion process. Surprisingly, in herpesviruses, these functions are distributed among multiple proteins: the conserved fusogen gB, the conserved gH/gL heterodimer of poorly defined function, and various non-conserved receptor-binding proteins. We summarize what is currently known about gB from two closely related herpesviruses, HSV-1 and HSV-2, with emphasis on the structure of the largely uncharted membrane interacting regions of this fusogen. We propose that the unusual mechanism of herpesvirus fusion could be linked to the unique architecture of gB.",2015 Dec 11,"['Cooper, Rebecca S.', 'Heldwein, Ekaterina E.']",Viruses,,,True
ed526e1eb5a7607af2803906e2f6d4e5bb2dff09,PMC,Potential Broad Spectrum Inhibitors of the Coronavirus 3CL(pro): A Virtual Screening and Structure-Based Drug Design Study,http://dx.doi.org/10.3390/v7122963,PMC4690886,26694449,CC BY,"Human coronaviruses represent a significant disease burden; however, there is currently no antiviral strategy to combat infection. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) less than 10 years later demonstrates the potential of coronaviruses to cross species boundaries and further highlights the importance of identifying novel lead compounds with broad spectrum activity. The coronavirus 3CL(pro) provides a highly validated drug target and as there is a high degree of sequence homology and conservation in main chain architecture the design of broad spectrum inhibitors is viable. The ZINC drugs-now library was screened in a consensus high-throughput pharmacophore modeling and molecular docking approach by Vina, Glide, GOLD and MM-GBSA. Molecular dynamics further confirmed results obtained from structure-based techniques. A highly defined hit-list of 19 compounds was identified by the structure-based drug design methodologies. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds is bioactive is excellent. Additionally, the compounds segregate into 15 significantly dissimilar (p < 0.05) clusters based on shape and features, which represent valuable scaffolds that can be used as a basis for future anti-coronaviral inhibitor discovery experiments. Importantly though, the enriched subset of 19 compounds identified from the larger library has to be validated experimentally.",2015 Dec 15,"['Berry, Michael', 'Fielding, Burtram C.', 'Gamieldien, Junaid']",Viruses,,,True
e2b5298da8d9d86daf286304637a644139dc6dc1,PMC,Glucose-6-Phosphate Dehydrogenase Enhances Antiviral Response through Downregulation of NADPH Sensor HSCARG and Upregulation of NF-κB Signaling,http://dx.doi.org/10.3390/v7122966,PMC4690889,26694452,CC BY,"Glucose-6-phosphate dehydrogenase (G6PD)-deficient cells are highly susceptible to viral infection. This study examined the mechanism underlying this phenomenon by measuring the expression of antiviral genes—tumor necrosis factor alpha (TNF-α) and GTPase myxovirus resistance 1 (MX1)—in G6PD-knockdown cells upon human coronavirus 229E (HCoV-229E) and enterovirus 71 (EV71) infection. Molecular analysis revealed that the promoter activities of TNF-α and MX1 were downregulated in G6PD-knockdown cells, and that the IκB degradation and DNA binding activity of NF-κB were decreased. The HSCARG protein, a nicotinamide adenine dinucleotide phosphate (NADPH) sensor and negative regulator of NF-κB, was upregulated in G6PD-knockdown cells with decreased NADPH/NADP(+) ratio. Treatment of G6PD-knockdown cells with siRNA against HSCARG enhanced the DNA binding activity of NF-κB and the expression of TNF-α and MX1, but suppressed the expression of viral genes; however, the overexpression of HSCARG inhibited the antiviral response. Exogenous G6PD or IDH1 expression inhibited the expression of HSCARG, resulting in increased expression of TNF-α and MX1 and reduced viral gene expression upon virus infection. Our findings suggest that the increased susceptibility of the G6PD-knockdown cells to viral infection was due to impaired NF-κB signaling and antiviral response mediated by HSCARG.",2015 Dec 17,"['Wu, Yi-Hsuan', 'Chiu, Daniel Tsun-Yee', 'Lin, Hsin-Ru', 'Tang, Hsiang-Yu', 'Cheng, Mei-Ling', 'Ho, Hung-Yao']",Viruses,,,True
91e6020c65dd5a92c89040f9e209d65e26ef2b7f,PMC,Therapeutic Targets for Neurodevelopmental Disorders Emerging from Animal Models with Perinatal Immune Activation,http://dx.doi.org/10.3390/ijms161226092,PMC4691039,26633355,CC BY,"Increasing epidemiological evidence indicates that perinatal infection with various viral pathogens enhances the risk for several psychiatric disorders. The pathophysiological significance of astrocyte interactions with neurons and/or gut microbiomes has been reported in neurodevelopmental disorders triggered by pre- and postnatal immune insults. Recent studies with the maternal immune activation or neonatal polyriboinosinic polyribocytidylic acid models of neurodevelopmental disorders have identified various candidate molecules that could be responsible for brain dysfunction. Here, we review the functions of several candidate molecules in neurodevelopment and brain function and discuss their potential as therapeutic targets for psychiatric disorders.",2015 Nov 27,"['Ibi, Daisuke', 'Yamada, Kiyofumi']",Int J Mol Sci,,,True
17cff89c1672094997155613467334c9b1b410e8,PMC,Plants as Factories for Human Pharmaceuticals: Applications and Challenges,http://dx.doi.org/10.3390/ijms161226122,PMC4691069,26633378,CC BY,"Plant molecular farming (PMF), defined as the practice of using plants to produce human therapeutic proteins, has received worldwide interest. PMF has grown and advanced considerably over the past two decades. A number of therapeutic proteins have been produced in plants, some of which have been through pre-clinical or clinical trials and are close to commercialization. Plants have the potential to mass-produce pharmaceutical products with less cost than traditional methods. Tobacco-derived antibodies have been tested and used to combat the Ebola outbreak in Africa. Genetically engineered immunoadhesin (DPP4-Fc) produced in green plants has been shown to be able to bind to MERS-CoV (Middle East Respiratory Syndrome), preventing the virus from infecting lung cells. Biosafety concerns (such as pollen contamination and immunogenicity of plant-specific glycans) and costly downstream extraction and purification requirements, however, have hampered PMF production from moving from the laboratory to industrial application. In this review, the challenges and opportunities of PMF are discussed. Topics addressed include; transformation and expression systems, plant bioreactors, safety concerns, and various opportunities to produce topical applications and health supplements.",2015 Dec 2,"['Yao, Jian', 'Weng, Yunqi', 'Dickey, Alexia', 'Wang, Kevin Yueju']",Int J Mol Sci,,,True
a263f1ec26e982b0f070dcb721f6e51e7d970889,PMC,A Porcine Epidemic Diarrhea Virus Outbreak in One Geographic Region of the United States: Descriptive Epidemiology and Investigation of the Possibility of Airborne Virus Spread,http://dx.doi.org/10.1371/journal.pone.0144818,PMC4692406,26709512,CC0,"This study describes a spring 2013 outbreak of porcine epidemic diarrhea virus (PEDv), using data from 222 swine sites in 14 counties area in 4 contiguous states in the United States. During the outbreak, the premises-level incidence of PEDv was 40.5 percent (90/222 sites). One of the three companies from which data were collected had a lower incidence (19.5 percent) than the other two companies (41.1 and 47.2 percent). Sow sites had the highest incidence of PEDv during the outbreak (80.0 percent). Spatial analysis showed that PEDv was clustered rather than randomly distributed, which suggested that sites near a positive site had increased risk of acquiring PEDv infection. Meteorological data were used to investigate the hypothesis that PEDv was spread by air. If airborne dissemination played a role in this outbreak, we would expect the direction of disease spread to correlate with the predominant wind direction. Two methods were used to determine the direction of disease spread—linear direction mean analysis in ArcGIS and the direction test in ClusterSeer. The former method indicated PEDv spread was south to slightly southwest, and the latter indicated spread was to the southeast. The predominant wind direction during the month of the outbreak was toward the south, with some southeast and southwest winds; the strongest wind gusts were toward the southwest. These findings support the hypothesis that PEDv was spread by air. The results, however, should be interpreted cautiously because we did not have information on direct and indirect contacts between sites, such as movement of trucks, feed, pigs or people. These types of contacts should be evaluated before pathogen spread is attributed to airborne mechanisms. Although this study did not provide a definitive assessment of airborne spread of PEDv, we believe the findings justify additional research to investigate this potential mechanism of transmission.",2015 Dec 28,"['Beam, Andrea', 'Goede, Dane', 'Fox, Andrew', 'McCool, Mary Jane', 'Wall, Goldlin', 'Haley, Charles', 'Morrison, Robert']",PLoS One,,,True
4c6efd303141e36db6479eda5dc5d2a379e6bcd9,PMC,Evolutionary Insights into IL17A in Lagomorphs,http://dx.doi.org/10.1155/2015/367670,PMC4692990,26788019,CC BY,"In leporids, IL17A had been implicated in the host defense against extracellular pathogens, such as Francisella tularensis that infects hares and rabbits and causes the zoonotic disease tularemia. Here, we studied IL17A from five lagomorphs, European rabbit, pygmy rabbit, brush rabbit, European brown hare, and American pika. We observed that this protein is highly conserved between these species, with a similarity of 97–99% in leporids and ~88% between leporids and American pika. The exon/intron structure, N-glycosylation sites, and cysteine residues are conserved between lagomorphs. However, at codon 88, one of the interaction sites between IL17A and its receptor IL17RA, there is an Arg>Pro mutation that only occurs in European rabbit and European brown hare. This could induce critical alterations in the IL17A structure and conformation and consequently modify its function. The differences observed between leporids and humans or rodents might also represent important alterations in protein structure and function. In addition, as for other interleukins, IL17A sequences of human and European rabbit are more closely related than the sequences of human and mouse or European rabbit and mouse. This study gives further support to the hypothesis that European rabbit might be a more suitable animal model for studies on human IL17.",2015 Dec 15,"['Neves, Fabiana', 'Abrantes, Joana', 'Almeida, Tereza', 'Costa, Paulo P.', 'Esteves, Pedro J.']",Mediators Inflamm,,,True
ba56c984234f222a42689dc2830c757add96b345,PMC,Full Genomic Characterization of a Saffold Virus Isolated in Peru,http://dx.doi.org/10.3390/pathogens4040816,PMC4693166,26610576,CC BY,While studying respiratory infections of unknown etiology we detected Saffold virus in an oropharyngeal swab collected from a two-year-old female suffering from diarrhea and respiratory illness. The full viral genome recovered by deep sequencing showed 98% identity to a previously described Saffold strain isolated in Japan. Phylogenetic analysis confirmed the Peruvian Saffold strain belongs to genotype 3 and is most closely related to strains that have circulated in Asia. This is the first documented case report of Saffold virus in Peru and the only complete genomic characterization of a Saffold-3 isolate from the Americas.,2015 Nov 20,"['Leguia, Mariana', 'Loyola, Steev', 'Rios, Jane', 'Juarez, Diana', 'Guevara, Carolina', 'Silva, Maria', 'Prieto, Karla', 'Wiley, Michael', 'Kasper, Matthew R.', 'Palacios, Gustavo', 'Bausch, Daniel G.']",Pathogens,,,True
bd2a3e44148e47e73516efdce7a8692b0f93fc3c,PMC,Full Genomic Characterization of a Saffold Virus Isolated in Peru,http://dx.doi.org/10.3390/pathogens4040816,PMC4693166,26610576,CC BY,While studying respiratory infections of unknown etiology we detected Saffold virus in an oropharyngeal swab collected from a two-year-old female suffering from diarrhea and respiratory illness. The full viral genome recovered by deep sequencing showed 98% identity to a previously described Saffold strain isolated in Japan. Phylogenetic analysis confirmed the Peruvian Saffold strain belongs to genotype 3 and is most closely related to strains that have circulated in Asia. This is the first documented case report of Saffold virus in Peru and the only complete genomic characterization of a Saffold-3 isolate from the Americas.,2015 Nov 20,"['Leguia, Mariana', 'Loyola, Steev', 'Rios, Jane', 'Juarez, Diana', 'Guevara, Carolina', 'Silva, Maria', 'Prieto, Karla', 'Wiley, Michael', 'Kasper, Matthew R.', 'Palacios, Gustavo', 'Bausch, Daniel G.']",Pathogens,,,False
8bae8e6308d50b3a053a98be3b0fd641c775c1ca,PMC,Two novel regulators of N‐acetyl‐galactosamine utilization pathway and distinct roles in bacterial infections,http://dx.doi.org/10.1002/mbo3.307,PMC4694137,26540018,CC BY,"Bacterial pathogens can exploit metabolic pathways to facilitate their successful infection cycles, but little is known about roles of d‐galactosamine (GalN)/N‐acetyl‐d‐galactosamine (GalNAc) catabolism pathway in bacterial pathogenesis. Here, we report the genomic reconstruction of GalN/GalNAc utilization pathway in Streptococci and the diversified aga regulons. We delineated two new paralogous AgaR regulators for the GalN/GalNAc catabolism pathway. The electrophoretic mobility shift assays experiment demonstrated that AgaR2 (AgaR1) binds the predicted palindromes, and the combined in vivo data from reverse transcription quantitative polymerase chain reaction and RNA‐seq suggested that AgaR2 (not AgaR1) can effectively repress the transcription of the target genes. Removal of agaR2 (not agaR1) from Streptococcus suis 05ZYH33 augments significantly the abilities of both adherence to Hep‐2 cells and anti‐phagocytosis against RAW264.7 macrophage. As anticipated, the dysfunction in AgaR2‐mediated regulation of S. suis impairs its pathogenicity in experimental models of both mice and piglets. Our finding discovered two novel regulators specific for GalN/GalNAc catabolism and assigned them distinct roles into bacterial infections. To the best of our knowledge, it might represent a first paradigm that links the GalN/GalNAc catabolism pathway to bacterial pathogenesis.",2015 Nov 5,"['Zhang, Huimin', 'Ravcheev, Dmitry A.', 'Hu, Dan', 'Zhang, Fengyu', 'Gong, Xiufang', 'Hao, Lina', 'Cao, Min', 'Rodionov, Dmitry A.', 'Wang, Changjun', 'Feng, Youjun']",Microbiologyopen,,,True
26e8ef0fab0bc606adadae018a73d8490c8e1cd5,PMC,Knock out of the BASIGIN/CD147 chaperone of lactate/H+ symporters disproves its pro-tumour action via extracellular matrix metalloproteases (MMPs) induction,,PMC4694784,26284589,CC BY,"BASIGIN/CD147/EMMPRIN is a multifunctional transmembrane glycoprotein strongly expressed in tumours. BASIGIN controls tumour metabolism, particularly glycolysis by facilitating lactic acid export through the two monocarboxylate transporters MCT1 and hypoxia-inducible MCT4. However, before being recognized as a co-carrier of MCTs, BASIGIN was described as an inducer of extracellular matrix metalloproteases (MMPs). Early on, a model emerged in which, tumour cells use the extracellular domain of BASIGIN to recognize and stimulate neighbouring fibroblasts to produce MMPs. However, this model has remained hypothetical since a direct link between BASIGIN and MMPs production has not yet been clearly established. To validate the BASIGIN/MMP hypothesis, we developed BASIGIN knockouts in three human tumour cell lines derived from glioma, colon, and lung adenocarcinoma. By using co-culture experiments of either human or mouse fibroblasts and tumour cell lines we showed, contrary to what has been abundantly published, that the disruption of BASIGIN in tumour cells and in MEFs has no action on the production of MMPs. Our findings do not support the notion that the pro-tumoural action of BASIGIN is mediated via induction of MMPs. Therefore, we propose that to date, the strongest pro-tumoural action of BASIGIN is mediated through the control of fermentative glycolysis.",2015 May 29,"['Marchiq, Ibtissam', 'Albrengues, Jean', 'Granja, Sara', 'Gaggioli, Cédric', 'Pouysségur, Jacques', 'Simon, Marie-Pierre']",Oncotarget,,,True
77c8f24d21f25774e383052c028b90b178c7b3d8,PMC,Intracellular Mono-ADP-Ribosylation in Signaling and Disease,http://dx.doi.org/10.3390/cells4040569,PMC4695847,26426055,CC BY,"A key process in the regulation of protein activities and thus cellular signaling pathways is the modification of proteins by post-translational mechanisms. Knowledge about the enzymes (writers and erasers) that attach and remove post-translational modifications, the targets that are modified and the functional consequences elicited by specific modifications, is crucial for understanding cell biological processes. Moreover detailed knowledge about these mechanisms and pathways helps to elucidate the molecular causes of various diseases and in defining potential targets for therapeutic approaches. Intracellular adenosine diphosphate (ADP)-ribosylation refers to the nicotinamide adenine dinucleotide (NAD(+))-dependent modification of proteins with ADP-ribose and is catalyzed by enzymes of the ARTD (ADP-ribosyltransferase diphtheria toxin like, also known as PARP) family as well as some members of the Sirtuin family. Poly-ADP-ribosylation is relatively well understood with inhibitors being used as anti-cancer agents. However, the majority of ARTD enzymes and the ADP-ribosylating Sirtuins are restricted to catalyzing mono-ADP-ribosylation. Although writers, readers and erasers of intracellular mono-ADP-ribosylation have been identified only recently, it is becoming more and more evident that this reversible post-translational modification is capable of modulating key intracellular processes and signaling pathways. These include signal transduction mechanisms, stress pathways associated with the endoplasmic reticulum and stress granules, and chromatin-associated processes such as transcription and DNA repair. We hypothesize that mono-ADP-ribosylation controls, through these different pathways, the development of cancer and infectious diseases.",2015 Sep 25,"['Bütepage, Mareike', 'Eckei, Laura', 'Verheugd, Patricia', 'Lüscher, Bernhard']",Cells,,,True
0c58e0eb436a3d0cb4c5acfa41babc03b3dfe825,PMC,"Implementing a One Health approach to emerging infectious disease: reflections on the socio-political, ethical and legal dimensions",http://dx.doi.org/10.1186/s12889-015-2617-1,PMC4696140,26715066,CC BY,"BACKGROUND: ‘One Health’ represents a call for health researchers and practitioners at the human, animal and environmental interfaces to work together to mitigate the risks of emerging and re-emerging infectious diseases (EIDs). A One Health approach emphasizing inter-disciplinary co-operation is increasingly seen as necessary for effective EID control and prevention. There are, however, socio-political, ethical and legal challenges, which must be met by such a One Health approach. DISCUSSION: Based on the philosophical review and critical analysis of scholarship around the theory and practice of One Health it is clear that EID events are not simply about pathogens jumping species barriers; they are comprised of complex and contingent sets of relations that involve socioeconomic and socio-political drivers and consequences with the latter extending beyond the impact of the disease. Therefore, the effectiveness of policies based on One Health depends on their implementation and alignment with or modification of public values. SUMMARY: Despite its strong motivating rationale, implementing a One Health approach in an integrated and considered manner can be challenging, especially in the face of a perceived crisis. The effective control and prevention of EIDs therefore requires: (i) social science research to improve understanding of how EID threats and responses play out; (ii) the development of an analytic framework that catalogues case experiences with EIDs, reflects their dynamic nature and promotes inter-sectoral collaboration and knowledge synthesis; (iii) genuine public engagement processes that promote transparency, education and capture people’s preferences; (iv) a set of practical principles and values that integrate ethics into decision-making procedures, against which policies and public health responses can be assessed; (v) integration of the analytic framework and the statement of principles and values outlined above; and (vi) a focus on genuine reform rather than rhetoric.",2015 Dec 29,"['Degeling, Chris', 'Johnson, Jane', 'Kerridge, Ian', 'Wilson, Andrew', 'Ward, Michael', 'Stewart, Cameron', 'Gilbert, Gwendolyn']",BMC Public Health,,,True
30d6338f9b3366f9d76e5cc76e6a79a4aa3f8c13,PMC,"First detection, clinical presentation and phylogenetic characterization of Porcine epidemic diarrhea virus in Austria",http://dx.doi.org/10.1186/s12917-015-0624-1,PMC4696200,26714453,CC BY,"BACKGROUND: Porcine epidemic diarrhea (PED) is a syndrome that is characterized by rapidly spreading watery diarrhea affecting pigs of all ages, but with major effects on suckling piglets. The disease, as well as the causative Alphacoronavirus, the Porcine epidemic diarrhea virus (PEDV), was first described in Europe in the 1970s and since then has spread over many Asian and American countries, where it recently led to devastating effects on swine health and pork industry. While the disease was seldom reported in Europe within the last few decades, a few recent reports re-emergence of PED in German pig farms. The hitherto isolated German strain seems to be closely related to a low pathogenic PEDV variant from the USA. This case report describes the first detection of PEDV in Austria. CASE PRESENTATION: Reduced feed uptake and occasional diarrhea were observed in December 2014 in a group of fattening pigs, kept on an Austrian swine farm. The concerned pigs had been recently purchased from Germany. Within a few weeks, diarrhea became apparent also in pigs of Austrian origin, which were kept in a different stable on the same farm. Gastrointestinal symptoms among fattening pigs were generally mild, quickly resolving and did not lead to death. PEDV RNA was identified by RT-qPCR in pooled feces and serum and PEDV antibodies were detectable in serum in both groups of pigs. Phylogenetic analysis of the nearly complete PEDV spike gene shows that the Austrian PEDV strain is highly similar to other strains involved in recent outbreaks in Western and Central Europe. CONCLUSION: This is the first report demonstrating the presence of PEDV in Austria. The virus was probably introduced by purchasing piglets from a German source, which underlines the significance of trans-boundary animal trade for the distribution of highly contagious diseases, such as PED. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0624-1) contains supplementary material, which is available to authorized users.",2015 Dec 30,"['Steinrigl, Adolf', 'Revilla Fernández, Sandra', 'Stoiber, Friedrich', 'Pikalo, Jutta', 'Sattler, Tatjana', 'Schmoll, Friedrich']",BMC Vet Res,,,True
ec955d5ff9dc3bdb037e561ee890c4c18fdb4272,PMC,Phylogenetic investigation of enteric bovine coronavirus in Ireland reveals partitioning between European and global strains,http://dx.doi.org/10.1186/s13620-015-0060-3,PMC4696222,26719792,CC BY,"BACKGROUND: Bovine coronavirus is a primary cause of neonatal calf diarrhea worldwide, and is also associated with acute diarrhea in adult cattle during the winter season. There are no reports on molecular characterization of bovine coronavirus in Ireland, and little data exists apart from serological studies. FINDINGS: In this study, 11 neonatal (mean age 9 days) calf BCoV strains from the south of Ireland were collected over a one year period and characterized using molecular methods. The spike gene which encodes a protein involved in viral entry, infectivity and immune response shows the most variability amongst the isolates and was subsequently selected for in depth analysis. Phylogenetic analysis of the spike gene revealed that the Irish strains clustered with novel BCoV strains from Europe in a unique clade, possibly indicating lineage partitioning. Direct analysis of alignments identified amino acid changes in the spike protein unique to the Irish clade. CONCLUSION: Thus, monitoring of bovine coronavirus in Ireland is important as the current isolates in circulation in the south of Ireland may be diverging from the available vaccine strain, which may have implications regarding future BCoV vaccine efficacy.",2015 Dec 30,"['Gunn, L.', 'Collins, P. J.', 'O’Connell, M. J.', 'O’Shea, H.']",Ir Vet J,,,True
272c6cc36e652db7f8d263194c13b2a5c92ed92e,PMC,"Pathosphere.org: pathogen detection and characterization through a web-based, open source informatics platform",http://dx.doi.org/10.1186/s12859-015-0840-5,PMC4696252,26714571,CC BY,"BACKGROUND: The detection of pathogens in complex sample backgrounds has been revolutionized by wide access to next-generation sequencing (NGS) platforms. However, analytical methods to support NGS platforms are not as uniformly available. Pathosphere (found at Pathosphere.org) is a cloud - based open - sourced community tool that allows for communication, collaboration and sharing of NGS analytical tools and data amongst scientists working in academia, industry and government. The architecture allows for users to upload data and run available bioinformatics pipelines without the need for onsite processing hardware or technical support. RESULTS: The pathogen detection capabilities hosted on Pathosphere were tested by analyzing pathogen-containing samples sequenced by NGS with both spiked human samples as well as human and zoonotic host backgrounds. Pathosphere analytical pipelines developed by Edgewood Chemical Biological Center (ECBC) identified spiked pathogens within a common sample analyzed by 454, Ion Torrent, and Illumina sequencing platforms. ECBC pipelines also correctly identified pathogens in human samples containing arenavirus in addition to animal samples containing flavivirus and coronavirus. These analytical methods were limited in the detection of sequences with limited homology to previous annotations within NCBI databases, such as parvovirus. Utilizing the pipeline-hosting adaptability of Pathosphere, the analytical suite was supplemented by analytical pipelines designed by the United States Army Medical Research Insititute of Infectious Diseases and Walter Reed Army Institute of Research (USAMRIID-WRAIR). These pipelines were implemented and detected parvovirus sequence in the sample that the ECBC iterative analysis previously failed to identify. CONCLUSIONS: By accurately detecting pathogens in a variety of samples, this work demonstrates the utility of Pathosphere and provides a platform for utilizing, modifying and creating pipelines for a variety of NGS technologies developed to detect pathogens in complex sample backgrounds. These results serve as an exhibition for the existing pipelines and web-based interface of Pathosphere as well as the plug-in adaptability that allows for integration of newer NGS analytical software as it becomes available. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0840-5) contains supplementary material, which is available to authorized users.",2015 Dec 29,"['Kilianski, Andy', 'Carcel, Patrick', 'Yao, Shijie', 'Roth, Pierce', 'Schulte, Josh', 'Donarum, Greg B.', 'Fochler, Ed T.', 'Hill, Jessica M.', 'Liem, Alvin T.', 'Wiley, Michael R.', 'Ladner, Jason T.', 'Pfeffer, Bradley P.', 'Elliot, Oliver', 'Petrosov, Alexandra', 'Jima, Dereje D.', 'Vallard, Tyghe G.', 'Melendrez, Melanie C.', 'Skowronski, Evan', 'Quan, Phenix-Lan', 'Lipkin, W. Ian', 'Gibbons, Henry S.', 'Hirschberg, David L.', 'Palacios, Gustavo F.', 'Rosenzweig, C. Nicole']",BMC Bioinformatics,,,True
5819ca9f401da096d402b6d1956a4fe6ba1c74b0,PMC,A simple novel device for air sampling by electrokinetic capture,http://dx.doi.org/10.1186/s40168-015-0141-2,PMC4696304,26715467,CC BY,"BACKGROUND: A variety of different sampling devices are currently available to acquire air samples for the study of the microbiome of the air. All have a degree of technical complexity that limits deployment. Here, we evaluate the use of a novel device, which has no technical complexity and is easily deployable. RESULTS: An air-cleaning device powered by electrokinetic propulsion has been adapted to provide a universal method for collecting samples of the aerobiome. Plasma-induced charge in aerosol particles causes propulsion to and capture on a counter-electrode. The flow of ions creates net bulk airflow, with no moving parts. A device and electrode assembly have been re-designed from air-cleaning technology to provide an average air flow of 120 lpm. This compares favorably with current air sampling devices based on physical air pumping. Capture efficiency was determined by comparison with a 0.4 μm polycarbonate reference filter, using fluorescent latex particles in a controlled environment chamber. Performance was compared with the same reference filter method in field studies in three different environments. For 23 common fungal species by quantitative polymerase chain reaction (qPCR), there was 100 % sensitivity and apparent specificity of 87 %, with the reference filter taken as “gold standard.” Further, bacterial analysis of 16S RNA by amplicon sequencing showed equivalent community structure captured by the electrokinetic device and the reference filter. Unlike other current air sampling methods, capture of particles is determined by charge and so is not controlled by particle mass. We analyzed particle sizes captured from air, without regard to specific analyte by atomic force microscopy: particles at least as low as 100 nM could be captured from ambient air. CONCLUSIONS: This work introduces a very simple plug-and-play device that can sample air at a high-volume flow rate with no moving parts and collect particles down to the sub-micron range. The performance of the device is substantially equivalent to capture by pumping through a filter for microbiome analysis by quantitative PCR and amplicon sequencing.",2015 Dec 27,"['Gordon, Julian', 'Gandhi, Prasanthi', 'Shekhawat, Gajendra', 'Frazier, Angel', 'Hampton-Marcell, Jarrad', 'Gilbert, Jack A.']",Microbiome,,,True
8de35b5317b0ebc437a5d5dbe94100f93ff88ab1,PMC,Moving pathogen genomics out of the lab and into the clinic: what will it take?,http://dx.doi.org/10.1186/s13073-015-0254-z,PMC4697326,26719100,CC BY,"Pathogen genomic analysis is a potentially transformative new approach to the clinical and public-health management of infectious diseases. Health systems investing in this technology will need to build infrastructure and develop policies that ensure genomic information can be generated, shared and acted upon in a timely manner.",2015 Dec 30,"['Luheshi, Leila M.', 'Raza, Sobia', 'Peacock, Sharon J.']",Genome Med,,,True
97bdba1d4a122241576c1e180ca7ce848cb657a3,PMC,Evaluation of humoral immune status in porcine epidemic diarrhea virus (PEDV) infected sows under field conditions,http://dx.doi.org/10.1186/s13567-015-0285-x,PMC4699368,26667229,CC BY,"Porcine epidemic diarrhea virus (PEDV) is an economically devastating enteric disease in the swine industry. The virus infects pigs of all ages, but it cause severe clinical disease in neonatal suckling pigs with up to 100% mortality. Currently, available vaccines are not completely effective and feedback methods utilizing PEDV infected material has variable success in preventing reinfection. Comprehensive information on the levels and duration of effector/memory IgA and IgG antibody secreting B cell response in the intestines and lymphoid organs of PEDV-infected sows, and their association with specific antibody levels in clinical samples such as plasma, oral fluid, and feces is important. Therefore, our goal in this study was to quantify PEDV specific IgA and IgG B cell responses in sows at approximately 1 and 6 months post-infection in commercial swine herds, including parity one and higher sows. Our data indicated that evaluation of both PEDV specific IgA and IgG antibody levels in the plasma and oral fluid (but not feces) samples is beneficial in disease diagnosis. PEDV specific B cell response in the intestine and spleen of infected sows decline by 6 months, and this associates with specific antibody levels in the plasma and oral fluid samples; but the virus neutralization titers in plasma remains high beyond 6 months post-infection. In conclusion, in sows infected with PEDV the presence of effector/memory B cell response and strong virus neutralization titers in plasma up to 6 months post-infection, suggests their potential to protect sows from reinfection and provide maternal immunity to neonates, but challenge studies are required to confirm such responses.",2015 Dec 14,"['Ouyang, Kang', 'Shyu, Duan-Liang', 'Dhakal, Santosh', 'Hiremath, Jagadish', 'Binjawadagi, Basavaraj', 'Lakshmanappa, Yashavanth S.', 'Guo, Rui', 'Ransburgh, Russell', 'Bondra, Kathryn M.', 'Gauger, Phillip', 'Zhang, Jianqiang', 'Specht, Terry', 'Gilbertie, Aaron', 'Minton, William', 'Fang, Ying', 'Renukaradhya, Gourapura J.']",Vet Res,,,True
37e2ecefeffdf8d95f1509809b59fe0464abba44,PMC,"Prostaglandin E(2) stimulates normal bronchial epithelial cell growth through induction of c-Jun and PDK1, a kinase implicated in oncogenesis",http://dx.doi.org/10.1186/s12931-015-0309-0,PMC4699375,26684827,CC BY,"BACKGROUND: Cyclooxygenase-2-derived prostaglandin E(2) (PGE(2)), a bioactive eicosanoid, has been implicated in many biological processes including reproduction, inflammation and tumor growth. We previously showed that PGE(2) stimulated lung cancer cell growth and progression through PGE(2) receptor EP2/EP4-mediated kinase signaling pathways. However, the role of PGE(2) in controlling lung airway epithelial cell phenotype remains unknown. We evaluated the effects of c-Jun and 3-phosphoinositede dependent protein kinase-1 (PDK1) in mediating epithelial cell hyperplasia induced by PGE(2). METHOD: The bronchial epithelial cell lines BEAS-2B and HBEc14-KT were cultured and then treated with PGE(2). PDK1 small interfering RNA (siRNA) and a PDK1 inhibitor, an antagonist of the PGE(2) receptor subtype EP4 and EP4 siRNA, c-Jun siRNA, and overexpressions of c-Jun and PDK1 have been used to evaluate the effects on cell proliferation. RESULTS: We demonstrated that PGE(2) increased normal bronchial epithelial cell proliferation through induction of PDK1, an ankyrin repeat-containing Ser/Thr kinase implicated in the induction of apoptosis and the suppression of tumor growth. PDK1 siRNA and a PDK1 inhibitor blocked the effects of PGE(2) on normal cell growth. The PGE(2)-induced PDK1 expression was blocked by an antagonist of the PGE(2) receptor subtype EP4 and by EP4 siRNA. In addition, we showed that induction of PDK1 by PGE(2) was associated with induction of the transcription factor, c-Jun protein. Silencing of c-Jun using siRNA and point mutations of c-Jun sites in the PDK1 gene promoter resulted in blockade of PDK1 expression and promoter activity induced by PGE(2). In contrast, overexpression of c-Jun induced PDK1 gene promoter activity and expression followed increased cell proliferation. CONCLUSION: PGE(2) increases normal bronchial epithelial cell proliferation through increased PDK1 gene expression that is dependent on EP4 and induction of c-Jun. Therewith, our data suggest a new role of c-Jun and PDK1 in mediating epithelial cell hyperplasia induced by PGE(2).",2015 Dec 18,"['Fan, Yu', 'Wang, Ye', 'Wang, Ke']",Respir Res,,,True
25ad3917e35438350dc5fdd7f64a4a1cdaea39f9,PMC,The Vietnam Initiative on Zoonotic Infections (VIZIONS): A Strategic Approach to Studying Emerging Zoonotic Infectious Diseases,http://dx.doi.org/10.1007/s10393-015-1061-0,PMC4700077,26403795,CC BY,"The effect of newly emerging or re-emerging infectious diseases of zoonotic origin in human populations can be potentially catastrophic, and large-scale investigations of such diseases are highly challenging. The monitoring of emergence events is subject to ascertainment bias, whether at the level of species discovery, emerging disease events, or disease outbreaks in human populations. Disease surveillance is generally performed post hoc, driven by a response to recent events and by the availability of detection and identification technologies. Additionally, the inventory of pathogens that exist in mammalian and other reservoirs is incomplete, and identifying those with the potential to cause disease in humans is rarely possible in advance. A major step in understanding the burden and diversity of zoonotic infections, the local behavioral and demographic risks of infection, and the risk of emergence of these pathogens in human populations is to establish surveillance networks in populations that maintain regular contact with diverse animal populations, and to simultaneously characterize pathogen diversity in human and animal populations. Vietnam has been an epicenter of disease emergence over the last decade, and practices at the human/animal interface may facilitate the likelihood of spillover of zoonotic pathogens into humans. To tackle the scientific issues surrounding the origins and emergence of zoonotic infections in Vietnam, we have established The Vietnam Initiative on Zoonotic Infections (VIZIONS). This countrywide project, in which several international institutions collaborate with Vietnamese organizations, is combining clinical data, epidemiology, high-throughput sequencing, and social sciences to address relevant one-health questions. Here, we describe the primary aims of the project, the infrastructure established to address our scientific questions, and the current status of the project. Our principal objective is to develop an integrated approach to the surveillance of pathogens circulating in both human and animal populations and assess how frequently they are exchanged. This infrastructure will facilitate systematic investigations of pathogen ecology and evolution, enhance understanding of viral cross-species transmission events, and identify relevant risk factors and drivers of zoonotic disease emergence.",2015 Sep 24,"['Rabaa, Maia A.', 'Tue, Ngo Tri', 'Phuc, Tran My', 'Carrique-Mas, Juan', 'Saylors, Karen', 'Cotten, Matthew', 'Bryant, Juliet E.', 'Nghia, Ho Dang Trung', 'Cuong, Nguyen Van', 'Pham, Hong Anh', 'Berto, Alessandra', 'Phat, Voong Vinh', 'Dung, Tran Thi Ngoc', 'Bao, Long Hoang', 'Hoa, Ngo Thi', 'Wertheim, Heiman', 'Nadjm, Behzad', 'Monagin, Corina', 'van Doorn, H. Rogier', 'Rahman, Motiur', 'Tra, My Phan Vu', 'Campbell, James I.', 'Boni, Maciej F.', 'Tam, Pham Thi Thanh', 'van der Hoek, Lia', 'Simmonds, Peter', 'Rambaut, Andrew', 'Toan, Tran Khanh', 'Van Vinh Chau, Nguyen', 'Hien, Tran Tinh', 'Wolfe, Nathan', 'Farrar, Jeremy J.', 'Thwaites, Guy', 'Kellam, Paul', 'Woolhouse, Mark E. J.', 'Baker, Stephen']",Ecohealth,,,True
d5b1fcbc43967a2f648462695d8c0a169aed6105,PMC,Ultrastructure and lipid composition of detergent-resistant membranes derived from mammalian sperm and two types of epithelial cells,http://dx.doi.org/10.1007/s00441-015-2272-y,PMC4700079,26378009,CC BY,"Lipid rafts are micro-domains of ordered lipids (L(o) phase) in biological membranes. The L(o) phase of cellular membranes can be isolated from disordered lipids (L(d) phase) after treatment with 1 % Triton X-100 at 4 °C in which the L(o) phase forms the detergent-resistant membrane (DRM) fraction. The lipid composition of DRM derived from Madin-Darby canine kidney (MDCK) cells, McArdle cells and porcine sperm is compared with that of the whole cell. Remarkably, the unsaturation and chain length degree of aliphatic chains attached to phospholipids is virtually the same between DRM and whole cells. Cholesterol and sphingomyelin were enriched in DRMs but to a cell-specific molar ratio. Sulfatides (sphingolipids from MDCK cells) were enriched in the DRM while a seminolipid (an alkylacylglycerolipid from sperm) was depleted from the DRM. Treatment with <5 mM methyl-ß-cyclodextrin (MBCD) caused cholesterol removal from the DRM without affecting the composition and amount of the phospholipid while higher levels disrupted the DRM. The substantial amount of (poly)unsaturated phospholipids in DRMs as well as a low stoichiometric amount of cholesterol suggest that lipid rafts in biological membranes are more fluid and dynamic than previously anticipated. Using negative staining, ultrastructural features of DRM were monitored and in all three cell types the DRMs appeared as multi-lamellar vesicular structures with a similar morphology. The detergent resistance is a result of protein–cholesterol and sphingolipid interactions allowing a relatively passive attraction of phospholipids to maintain the L(o) phase. For this special issue, the relevance of our findings is discussed in a sperm physiological context.",2016 Sep 16,"['van Gestel, Renske A.', 'Brouwers, Jos F.', 'Ultee, Anton', 'Helms, J. Bernd', 'Gadella, Bart M.']",Cell Tissue Res,,,True
0e08edfdafcee24569ce5be73cec8acb26142ba8,PMC,Recombinant Dengue virus protein NS2B alters membrane permeability in different membrane models,http://dx.doi.org/10.1186/s12985-015-0456-4,PMC4700614,26728778,CC BY,"BACKGROUND: One of the main phenomena occurring in cellular membranes during virus infection is a change in membrane permeability. It has been observed that numerous viral proteins can oligomerize and form structures known as viroporins that alter the permeability of membranes. Previous findings have identified such proteins in cells infected with Japanese encephalitis virus (JEV), a member of the same family that Dengue virus (DENV) belongs to (Flaviviridae). In the present work, we investigated whether the small hydrophobic DENV protein NS2B serves a viroporin function. METHODS: We cloned the DENV NS2B sequence and expressed it in a bacterial expression system. Subsequently, we evaluated the effect of DENV NS2B on membranes when NS2B was overexpressed, measured bacterial growth restriction, and evaluated changes of permeability to hygromycin. The NS2B protein was purified by affinity chromatography, and crosslinking assays were performed to determine the presence of oligomers. Hemolysis assays and transmission electron microscopy were performed to identify structures involved in permeability changes. RESULTS: The DENV-2 NS2B protein showed similitude with the JEV viroporin. The DENV-2 NS2B protein possessed the ability to change the membrane permeability in bacteria, to restrict bacterial cell growth, and to enable membrane permeability to hygromycin B. The NS2B protein formed trimers that could participate in cell lysis and generate organized structures on eukaryotes membranes. CONCLUSIONS: Our data suggest that the DENV-2 NS2B viral protein is capable of oligomerizing and organizing to form pore-like structures in different lipid environments, thereby modifying the permeability of cell membranes.",2016 Jan 4,"['León-Juárez, Moisés', 'Martínez-Castillo, Macario', 'Shrivastava, Gaurav', 'García-Cordero, Julio', 'Villegas-Sepulveda, Nicolás', 'Mondragón-Castelán, Mónica', 'Mondragón-Flores, Ricardo', 'Cedillo-Barrón, Leticia']",Virol J,,,True
fd19cfef82dc2fd1ee48be9b10563d681610c000,PMC,Lys-315 at the Interfaces of Diagonal Subunits of δ-Crystallin Plays a Critical Role in the Reversibility of Folding and Subunit Assembly,http://dx.doi.org/10.1371/journal.pone.0145957,PMC4701392,26731266,CC BY,"δ-Crystallin is the major structural protein in avian eye lenses and is homologous to the urea cycle enzyme argininosuccinate lyase. This protein is structurally assembled as double dimers. Lys-315 is the only residue which is arranged symmetrically at the diagonal subunit interfaces to interact with each other. This study found that wild-type protein had both dimers and monomers present in 2–4 M urea whilst only monomers of the K315A mutant were observed under the same conditions, as judged by sedimentation velocity analysis. The assembly of monomeric K315A mutant was reversible in contrast to wild-type protein. Molecular dynamics simulations showed that the dissociation of primary dimers is prior to the diagonal dimers in wild-type protein. These results suggest the critical role of Lys-315 in stabilization of the diagonal dimer structure. Guanidinium hydrochloride (GdmCl) denatured wild-type or K315A mutant protein did not fold into functional protein. However, the urea dissociated monomers of K315A mutant protein in GdmCl were reversible folding through a multiple steps mechanism as measured by tryptophan and ANS fluorescence. Two partly unfolded intermediates were detected in the pathway. Refolding of the intermediates resulted in a conformation with greater amounts of hydrophobic regions exposed which was prone to the formation of protein aggregates. The formation of aggregates was not prevented by the addition of α-crystallin. These results highlight that the conformational status of the monomers is critical for determining whether reversible oligomerization or aggregate formation occurs.",2016 Jan 5,"['Huang, Chih-Wei', 'Lin, Hui-Chen', 'Chou, Chi-Yuan', 'Kao, Wei-Chuo', 'Chou, Wei-Yuan', 'Lee, Hwei-Jen']",PLoS One,,,True
1a465d982030d8f361dc914ff2defa359fdbe5f9,PMC,The recent ancestry of Middle East respiratory syndrome coronavirus in Korea has been shaped by recombination,http://dx.doi.org/10.1038/srep18825,PMC4702133,26732651,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe cases of human respiratory disease. Since 2012, the victims have mainly come from the Middle East countries or sporadically from some other geographical regions seeded by the travelers who visited the Middle East. Such an introduction through travelling led to the emergence of a MERS-CoV outbreak in Korea in May 2015, which caused more than 140 confirmed human cases in less than a month. Using 70 complete genome sequences of MERS-CoV isolates, including the most recent sequences for the Korean and Chinese isolates, we reconstructed the phylogenetic relationships of the complete genome and the individual protein coding regions. The Korean MERS-CoV strain clustered in the previously established Hafr-Al-Batin-1_2013 clade together with two Saudi Arabian and one Chinese strain sampled in 2015. Although these four strains remained monophyletic in the entire protein-coding region, this clade showed different phylogenetic relationships across the genome, indicating a shared unique recombination pattern that is different from previously reported putative recombination strains. Our findings suggest that the recent ancestor of the Korean and its related MERS-CoV strains is characterized by unique mosaic genome pattern that is different from other putative recombinants.",2016 Jan 6,"['Kim, Jin Il', 'Kim, You-Jin', 'Lemey, Philippe', 'Lee, Ilseob', 'Park, Sehee', 'Bae, Joon-Yong', 'Kim, Donghwan', 'Kim, Hyejin', 'Jang, Seok-Il', 'Yang, Jeong-Sun', 'Kim, Hak', 'Kim, Dae-Won', 'Nam, Jeong-Gu', 'Kim, Sung Soon', 'Kim, Kisoon', 'Myun Lee, Jae', 'Song, Man Ki', 'Song, Daesub', 'Chang, Jun', 'Hong, Kee-Jong', 'Bae, Yong-Soo', 'Song, Jin-Won', 'Lee, Joo-Shil', 'Park, Man-Seong']",Sci Rep,,,True
785f1bfe60d4c4773e6492752396fc4ce8f61865,PMC,The recent ancestry of Middle East respiratory syndrome coronavirus in Korea has been shaped by recombination,http://dx.doi.org/10.1038/srep18825,PMC4702133,26732651,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe cases of human respiratory disease. Since 2012, the victims have mainly come from the Middle East countries or sporadically from some other geographical regions seeded by the travelers who visited the Middle East. Such an introduction through travelling led to the emergence of a MERS-CoV outbreak in Korea in May 2015, which caused more than 140 confirmed human cases in less than a month. Using 70 complete genome sequences of MERS-CoV isolates, including the most recent sequences for the Korean and Chinese isolates, we reconstructed the phylogenetic relationships of the complete genome and the individual protein coding regions. The Korean MERS-CoV strain clustered in the previously established Hafr-Al-Batin-1_2013 clade together with two Saudi Arabian and one Chinese strain sampled in 2015. Although these four strains remained monophyletic in the entire protein-coding region, this clade showed different phylogenetic relationships across the genome, indicating a shared unique recombination pattern that is different from previously reported putative recombination strains. Our findings suggest that the recent ancestor of the Korean and its related MERS-CoV strains is characterized by unique mosaic genome pattern that is different from other putative recombinants.",2016 Jan 6,"['Kim, Jin Il', 'Kim, You-Jin', 'Lemey, Philippe', 'Lee, Ilseob', 'Park, Sehee', 'Bae, Joon-Yong', 'Kim, Donghwan', 'Kim, Hyejin', 'Jang, Seok-Il', 'Yang, Jeong-Sun', 'Kim, Hak', 'Kim, Dae-Won', 'Nam, Jeong-Gu', 'Kim, Sung Soon', 'Kim, Kisoon', 'Myun Lee, Jae', 'Song, Man Ki', 'Song, Daesub', 'Chang, Jun', 'Hong, Kee-Jong', 'Bae, Yong-Soo', 'Song, Jin-Won', 'Lee, Joo-Shil', 'Park, Man-Seong']",Sci Rep,,,True
0ffbcddbc1c2527eca81dc62b12e587ab61ff4d0,PMC,Intubating Ebola Patients: Technical Limitations of Extensive Personal Protective Equipment,http://dx.doi.org/10.5811/westjem.2015.10.28779,PMC4703159,26759639,CC BY,,2015 Dec 14,"['Wiechmann, Warren', 'Toohey, Shannon', 'Majestic, Cassandra', 'Boysen-Osborn, Megan']",West J Emerg Med,,,True
d4d885e748fc8335d359da08f2ef0370103f98c7,PMC,A general strategy to inhibiting viral −1 frameshifting based on upstream attenuation duplex formation,http://dx.doi.org/10.1093/nar/gkv1307,PMC4705660,26612863,CC BY,"Viral −1 programmed ribosomal frameshifting (PRF) as a potential antiviral target has attracted interest because many human viral pathogens, including human immunodeficiency virus (HIV) and coronaviruses, rely on −1 PRF for optimal propagation. Efficient eukaryotic −1 PRF requires an optimally placed stimulator structure downstream of the frameshifting site and different strategies targeting viral −1 PRF stimulators have been developed. However, accessing particular −1 PRF stimulator information represents a bottle-neck in combating the emerging epidemic viral pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV). Recently, an RNA hairpin upstream of frameshifting site was shown to act as a cis-element to attenuate −1 PRF with mechanism unknown. Here, we show that an upstream duplex formed in-trans, by annealing an antisense to its complementary mRNA sequence upstream of frameshifting site, can replace an upstream hairpin to attenuate −1 PRF efficiently. This finding indicates that the formation of a proximal upstream duplex is the main determining factor responsible for −1 PRF attenuation and provides mechanistic insight. Additionally, the antisense-mediated upstream duplex approach downregulates −1 PRF stimulated by distinct −1 PRF stimulators, including those of MERS-CoV, suggesting its general application potential as a robust means to evaluating viral −1 PRF inhibition as soon as the sequence information of an emerging human coronavirus is available.",2016 Jan 8,"['Hu, Hao-Teng', 'Cho, Che-Pei', 'Lin, Ya-Hui', 'Chang, Kung-Yao']",Nucleic Acids Res,,,True
8d9c4ed5074e68cc26a911f277ad05fa0cd7c0e7,PMC,A general strategy to inhibiting viral −1 frameshifting based on upstream attenuation duplex formation,http://dx.doi.org/10.1093/nar/gkv1307,PMC4705660,26612863,CC BY,"Viral −1 programmed ribosomal frameshifting (PRF) as a potential antiviral target has attracted interest because many human viral pathogens, including human immunodeficiency virus (HIV) and coronaviruses, rely on −1 PRF for optimal propagation. Efficient eukaryotic −1 PRF requires an optimally placed stimulator structure downstream of the frameshifting site and different strategies targeting viral −1 PRF stimulators have been developed. However, accessing particular −1 PRF stimulator information represents a bottle-neck in combating the emerging epidemic viral pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV). Recently, an RNA hairpin upstream of frameshifting site was shown to act as a cis-element to attenuate −1 PRF with mechanism unknown. Here, we show that an upstream duplex formed in-trans, by annealing an antisense to its complementary mRNA sequence upstream of frameshifting site, can replace an upstream hairpin to attenuate −1 PRF efficiently. This finding indicates that the formation of a proximal upstream duplex is the main determining factor responsible for −1 PRF attenuation and provides mechanistic insight. Additionally, the antisense-mediated upstream duplex approach downregulates −1 PRF stimulated by distinct −1 PRF stimulators, including those of MERS-CoV, suggesting its general application potential as a robust means to evaluating viral −1 PRF inhibition as soon as the sequence information of an emerging human coronavirus is available.",2016 Jan 8,"['Hu, Hao-Teng', 'Cho, Che-Pei', 'Lin, Ya-Hui', 'Chang, Kung-Yao']",Nucleic Acids Res,,,True
fb2c5faf4ed6df2563f6f1830de5b7fbad0ead87,PMC,Clinical features of children hospitalized with influenza A and B infections during the 2012–2013 influenza season in Italy,http://dx.doi.org/10.1186/s12879-015-1333-x,PMC4705698,26743673,CC BY,"BACKGROUND: Influenza is a major public health issue worldwide. It is characterized by episodes of infection that involve hundreds of millions of people each year. Since that in the seasons 2010–2011 and 2011–2012 the circulation of FLUB was decreasing we evaluated the clinical presentation, demographic characteristics, admitting department, and length of stay in children who contracted influenza admitted to Bambino Gesù Children’s Hospital, during the 2012–2013 influenza season, with the aim to establish if the recover of FLUB was associated to a clinical worsening, in comparison with those due to FLUA. METHODS: A total of 133 respiratory specimens, collected from patients with symptoms of respiratory tract infections, positive for the Influenza A and B viruses (FLUA and B) were subtyped. Comparisons between the FLUA and FLUB groups were performed with the one-way ANOVA for continuous parametric variables, the Mann-Whitney test for non-parametric variables, or the Chi-Square test or Fisher’s exact test (if cells <5) for categorical variables. RESULTS: 87.09 % of the FLUA isolates were the H1N1 subtype and 12.90 % were H3N2. Among the FLUB isolates, 91.54 % were the B/Yamagata/16/88 lineage and 8.45 % were the B/Victoria/02/87 lineage. The largest number of FLUA/H1N1 cases was observed in children less than 1 years old, while the B/Yamagata/16/88 lineage was most prevalent in children 3–6 years old. Fever was a common symptom for both FLUA and B affected patients. However, respiratory symptoms were more prevalent in patients affected by FLUA. The median length of stay in the hospital was 5 days for FLUA and 3 days for FLUB. CONCLUSIONS: The clinical features correlated to different Influenza viruses, and relevant subtypes, were evaluated concluding that the increasing of FLUB in the season 2012–2013 was without any dramatic change in clinical manifestation. Our findings suggest, finally, that a stronger commitment to managing patients affected by FLUA is required, as the disease is more severe than FLUB.",2016 Jan 8,"['Mancinelli, Livia', 'Onori, Manuela', 'Concato, Carlo', 'Sorge, Roberto', 'Chiavelli, Stefano', 'Coltella, Luana', 'Raucci, Umberto', 'Reale, Antonio', 'Menichella, Donato', 'Russo, Cristina']",BMC Infect Dis,,,True
593333395be3bd94387b4e273cc8ed13b398d5c0,PMC,Deletion of Dystrophin In-Frame Exon 5 Leads to a Severe Phenotype: Guidance for Exon Skipping Strategies,http://dx.doi.org/10.1371/journal.pone.0145620,PMC4706350,26745801,CC BY,"Duchenne and Becker muscular dystrophy severity depends upon the nature and location of the DMD gene lesion and generally correlates with the dystrophin open reading frame. However, there are striking exceptions where an in-frame genomic deletion leads to severe pathology or protein-truncating mutations (nonsense or frame-shifting indels) manifest as mild disease. Exceptions to the dystrophin reading frame rule are usually resolved after molecular diagnosis on muscle RNA. We report a moderate/severe Becker muscular dystrophy patient with an in-frame genomic deletion of DMD exon 5. This mutation has been reported by others as resulting in Duchenne or Intermediate muscular dystrophy, and the loss of this in-frame exon in one patient led to multiple splicing events, including omission of exon 6, that disrupts the open reading frame and is consistent with a severe phenotype. The patient described has a deletion of dystrophin exon 5 that does not compromise recognition of exon 6, and although the deletion does not disrupt the reading frame, his clinical presentation is more severe than would be expected for classical Becker muscular dystrophy. We suggest that the dystrophin isoform lacking the actin-binding sequence encoded by exon 5 is compromised, reflected by the phenotype resulting from induction of this dystrophin isoform in mouse muscle in vivo. Hence, exon skipping to address DMD-causing mutations within DMD exon 5 may not yield an isoform that confers marked clinical benefit. Additional studies will be required to determine whether multi-exon skipping strategies could yield more functional dystrophin isoforms, since some BMD patients with larger in-frame deletions in this region have been reported with mild phenotypes.",2016 Jan 8,"['Toh, Zhi Yon Charles', 'Thandar Aung-Htut, May', 'Pinniger, Gavin', 'Adams, Abbie M.', 'Krishnaswarmy, Sudarsan', 'Wong, Brenda L.', 'Fletcher, Sue', 'Wilton, Steve D.']",PLoS One,,,True
b2fc5ae2867a0bc478fbd993c240bd7e59531e66,PMC,Self-assembling protein nanoparticles in the design of vaccines,http://dx.doi.org/10.1016/j.csbj.2015.11.001,PMC4706605,26862374,CC BY,"For over 100 years, vaccines have been one of the most effective medical interventions for reducing infectious disease, and are estimated to save millions of lives globally each year. Nevertheless, many diseases are not yet preventable by vaccination. This large unmet medical need demands further research and the development of novel vaccines with high efficacy and safety. Compared to the 19th and early 20th century vaccines that were made of killed, inactivated, or live-attenuated pathogens, modern vaccines containing isolated, highly purified antigenic protein subunits are safer but tend to induce lower levels of protective immunity. One strategy to overcome the latter is to design antigen nanoparticles: assemblies of polypeptides that present multiple copies of subunit antigens in well-ordered arrays with defined orientations that can potentially mimic the repetitiveness, geometry, size, and shape of the natural host-pathogen surface interactions. Such nanoparticles offer a collective strength of multiple binding sites (avidity) and can provide improved antigen stability and immunogenicity. Several exciting advances have emerged lately, including preclinical evidence that this strategy may be applicable for the development of innovative new vaccines, for example, protecting against influenza, human immunodeficiency virus, and respiratory syncytial virus. Here, we provide a concise review of a critical selection of data that demonstrate the potential of this field. In addition, we highlight how the use of self-assembling protein nanoparticles can be effectively combined with the emerging discipline of structural vaccinology for maximum impact in the rational design of vaccine antigens.",2015 Nov 26,"['López-Sagaseta, Jacinto', 'Malito, Enrico', 'Rappuoli, Rino', 'Bottomley, Matthew J.']",Comput Struct Biotechnol J,,,False
de9de0c48a6efdb714e714907ec3cff924dd28a5,PMC,Hemagglutinin-esterase-fusion (HEF) protein of influenza C virus,http://dx.doi.org/10.1007/s13238-015-0193-x,PMC4707155,26215728,CC BY,"Influenza C virus, a member of the Orthomyxoviridae family, causes flu-like disease but typically only with mild symptoms. Humans are the main reservoir of the virus, but it also infects pigs and dogs. Very recently, influenza C-like viruses were isolated from pigs and cattle that differ from classical influenza C virus and might constitute a new influenza virus genus. Influenza C virus is unique since it contains only one spike protein, the hemagglutinin-esterase-fusion glycoprotein HEF that possesses receptor binding, receptor destroying and membrane fusion activities, thus combining the functions of Hemagglutinin (HA) and Neuraminidase (NA) of influenza A and B viruses. Here we briefly review the epidemiology and pathology of the virus and the morphology of virus particles and their genome. The main focus is on the structure of the HEF protein as well as on its co- and post-translational modification, such as N-glycosylation, disulfide bond formation, S-acylation and proteolytic cleavage into HEF1 and HEF2 subunits. Finally, we describe the functions of HEF: receptor binding, esterase activity and membrane fusion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-015-0193-x) contains supplementary material, which is available to authorized users.",2016 Jan 28,"['Wang, Mingyang', 'Veit, Michael']",Protein Cell,,,False
4d140ee8fb10afd86c19fc5ad4749771dc37d146,PMC,Hemagglutinin-esterase-fusion (HEF) protein of influenza C virus,http://dx.doi.org/10.1007/s13238-015-0193-x,PMC4707155,26215728,CC BY,"Influenza C virus, a member of the Orthomyxoviridae family, causes flu-like disease but typically only with mild symptoms. Humans are the main reservoir of the virus, but it also infects pigs and dogs. Very recently, influenza C-like viruses were isolated from pigs and cattle that differ from classical influenza C virus and might constitute a new influenza virus genus. Influenza C virus is unique since it contains only one spike protein, the hemagglutinin-esterase-fusion glycoprotein HEF that possesses receptor binding, receptor destroying and membrane fusion activities, thus combining the functions of Hemagglutinin (HA) and Neuraminidase (NA) of influenza A and B viruses. Here we briefly review the epidemiology and pathology of the virus and the morphology of virus particles and their genome. The main focus is on the structure of the HEF protein as well as on its co- and post-translational modification, such as N-glycosylation, disulfide bond formation, S-acylation and proteolytic cleavage into HEF1 and HEF2 subunits. Finally, we describe the functions of HEF: receptor binding, esterase activity and membrane fusion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-015-0193-x) contains supplementary material, which is available to authorized users.",2016 Jan 28,"['Wang, Mingyang', 'Veit, Michael']",Protein Cell,,,True
1771673809c10324fde2768ce37d548a5077577f,PMC,"Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits",http://dx.doi.org/10.1371/journal.pone.0146932,PMC4709053,26752173,CC BY,"Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.",2016 Jan 11,"['Gruse, Jeannine', 'Kanitz, Ellen', 'Weitzel, Joachim M.', 'Tuchscherer, Armin', 'Stefaniak, Tadeusz', 'Jawor, Paulina', 'Wolffram, Siegfried', 'Hammon, Harald M.']",PLoS One,,,True
70b06768370d7d7c63a8f9a5042f67f8d9d02cf5,PMC,"Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits",http://dx.doi.org/10.1371/journal.pone.0146932,PMC4709053,26752173,CC BY,"Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.",2016 Jan 11,"['Gruse, Jeannine', 'Kanitz, Ellen', 'Weitzel, Joachim M.', 'Tuchscherer, Armin', 'Stefaniak, Tadeusz', 'Jawor, Paulina', 'Wolffram, Siegfried', 'Hammon, Harald M.']",PLoS One,,,False
dbd179cd05bcab8d52bcea618633deb27b6067b7,PMC,"Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits",http://dx.doi.org/10.1371/journal.pone.0146932,PMC4709053,26752173,CC BY,"Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.",2016 Jan 11,"['Gruse, Jeannine', 'Kanitz, Ellen', 'Weitzel, Joachim M.', 'Tuchscherer, Armin', 'Stefaniak, Tadeusz', 'Jawor, Paulina', 'Wolffram, Siegfried', 'Hammon, Harald M.']",PLoS One,,,False
39b7779027ca766d010009b54455331929b42d65,PMC,"Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits",http://dx.doi.org/10.1371/journal.pone.0146932,PMC4709053,26752173,CC BY,"Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.",2016 Jan 11,"['Gruse, Jeannine', 'Kanitz, Ellen', 'Weitzel, Joachim M.', 'Tuchscherer, Armin', 'Stefaniak, Tadeusz', 'Jawor, Paulina', 'Wolffram, Siegfried', 'Hammon, Harald M.']",PLoS One,,,False
41d4cb748a87a5bdd92a314aceea03950f8d7849,PMC,"Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits",http://dx.doi.org/10.1371/journal.pone.0146932,PMC4709053,26752173,CC BY,"Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.",2016 Jan 11,"['Gruse, Jeannine', 'Kanitz, Ellen', 'Weitzel, Joachim M.', 'Tuchscherer, Armin', 'Stefaniak, Tadeusz', 'Jawor, Paulina', 'Wolffram, Siegfried', 'Hammon, Harald M.']",PLoS One,,,False
3322a97885dd968ef3ca3dfc0e729f4206317afc,PMC,"Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits",http://dx.doi.org/10.1371/journal.pone.0146932,PMC4709053,26752173,CC BY,"Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.",2016 Jan 11,"['Gruse, Jeannine', 'Kanitz, Ellen', 'Weitzel, Joachim M.', 'Tuchscherer, Armin', 'Stefaniak, Tadeusz', 'Jawor, Paulina', 'Wolffram, Siegfried', 'Hammon, Harald M.']",PLoS One,,,False
f475fa6896d258457c8552fa960533b237ff7f18,PMC,"Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits",http://dx.doi.org/10.1371/journal.pone.0146932,PMC4709053,26752173,CC BY,"Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply.",2016 Jan 11,"['Gruse, Jeannine', 'Kanitz, Ellen', 'Weitzel, Joachim M.', 'Tuchscherer, Armin', 'Stefaniak, Tadeusz', 'Jawor, Paulina', 'Wolffram, Siegfried', 'Hammon, Harald M.']",PLoS One,,,False
58a0105289bbee3214a3fe6494ba86fce867df3a,PMC,Heterologous Immunity between Adenoviruses and Hepatitis C Virus: A New Paradigm in HCV Immunity and Vaccines,http://dx.doi.org/10.1371/journal.pone.0146404,PMC4709057,26751211,CC BY,"Adenoviruses (Ad) are commonly used as vectors for gene therapy and/or vaccine delivery. Recombinant Ad vectors are being tested as vaccines for many pathogens. We have made a surprising observation that peptides derived from various hepatitis C virus (HCV) antigens contain extensive regions of homology with multiple adenovirus proteins, and conclusively demonstrate that adenovirus vector can induce robust, heterologous cellular and humoral immune responses against multiple HCV antigens. Intriguingly, the induction of this cross-reactive immunity leads to significant reduction of viral loads in a recombinant vaccinia-HCV virus infected mouse model, supporting their role in antiviral immunity against HCV. Healthy human subjects with Ad-specific pre-existing immunity demonstrated cross-reactive cellular and humoral immune responses against multiple HCV antigens. These findings reveal the potential of a previously uncharacterized property of natural human adenovirus infection to dictate, modulate and/or alter the course of HCV infection upon exposure. This intrinsic property of adenovirus vectors to cross-prime HCV immunity can also be exploited to develop a prophylactic and/or therapeutic vaccine against HCV.",2016 Jan 11,"['Singh, Shakti', 'Vedi, Satish', 'Samrat, Subodh Kumar', 'Li, Wen', 'Kumar, Rakesh', 'Agrawal, Babita']",PLoS One,,,True
0e261abc97b50372753a8415e5a6b12da8a6be05,PMC,Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats,http://dx.doi.org/10.7554/eLife.11785,PMC4709267,26698106,CC0,"Biological factors that influence the host range and spillover of Ebola virus (EBOV) and other filoviruses remain enigmatic. While filoviruses infect diverse mammalian cell lines, we report that cells from African straw-colored fruit bats (Eidolon helvum) are refractory to EBOV infection. This could be explained by a single amino acid change in the filovirus receptor, NPC1, which greatly reduces the affinity of EBOV-NPC1 interaction. We found signatures of positive selection in bat NPC1 concentrated at the virus-receptor interface, with the strongest signal at the same residue that controls EBOV infection in Eidolon helvum cells. Our work identifies NPC1 as a genetic determinant of filovirus susceptibility in bats, and suggests that some NPC1 variations reflect host adaptations to reduce filovirus replication and virulence. A single viral mutation afforded escape from receptor control, revealing a pathway for compensatory viral evolution and a potential avenue for expansion of filovirus host range in nature. DOI: http://dx.doi.org/10.7554/eLife.11785.001",,"['Ng, Melinda', 'Ndungo, Esther', 'Kaczmarek, Maria E', 'Herbert, Andrew S', 'Binger, Tabea', 'Kuehne, Ana I', 'Jangra, Rohit K', 'Hawkins, John A', 'Gifford, Robert J', 'Biswas, Rohan', 'Demogines, Ann', 'James, Rebekah M', 'Yu, Meng', 'Brummelkamp, Thijn R', 'Drosten, Christian', 'Wang, Lin-Fa', 'Kuhn, Jens H', 'Müller, Marcel A', 'Dye, John M', 'Sawyer, Sara L', 'Chandran, Kartik']",eLife.; 4:e11785,,,True
aa080b8ad0bb2c4cd4e24f407b32f0e837c27432,PMC,Exogenous avian leukosis virus-induced activation of the ERK/AP1 pathway is required for virus replication and correlates with virus-induced tumorigenesis,http://dx.doi.org/10.1038/srep19226,PMC4709637,26754177,CC BY,"A proteomics approach was used to reveal the up-regulated proteins involved in the targeted mitogen-activated protein kinase (MAPK) signal transduction pathway in DF-1 cells after ALV subgroup J (ALV-J) infection. Next, we found that ALV-J CHN06 strain infection of DF-1 cells correlated with extracellular signal-regulated kinase 2 (ERK2) activation, which was mainly induced within 15 min, a very early stage of infection, and at a late infection stage, from 108 h to 132 h post-infection. Infection with other ALV subgroup (A/B) strains also triggered ERK/MAPK activation. Moreover, when activating ERK2, ALV subgroups A, B and J simultaneously induced the phosphorylation of c-Jun, an AP1 family member and p38 activation but had no obvious effect on JNK activation at either 15 min or 120 h. Interestingly, only PD98059 inhibited the ALV-induced c-Jun phosphorylation while SP600125 or SB203580 had no influence on c-Jun activation. Furthermore, the viral gp85 and gag proteins were found to contribute to ERK2/AP1 activation. Additionally, the specific ERK inhibitor, PD980509, significantly suppressed ALV replication, as evidenced by extremely low levels of ALV promoter activity and ALV-J protein expression. In vivo analysis of ERK2 activation in tumor cells derived from ALV-J-infected chicken demonstrated a strong correlation between ERK/MAPK activation and virus-associated tumorigenesis.",2016 Jan 12,"['Dai, Manman', 'Feng, Min', 'Ye, Yu', 'Wu, Xiaochan', 'Liu, Di', 'Liao, Ming', 'Cao, Weisheng']",Sci Rep,,,True
7c3ebae910203c1f867fad1b2c14c555fc3e263c,PMC,Crude incidence in two-phase designs in the presence of competing risks,http://dx.doi.org/10.1186/s12874-015-0103-1,PMC4710022,26754746,CC BY,"BACKGROUND: In many studies, some information might not be available for the whole cohort, some covariates, or even the outcome, might be ascertained in selected subsamples. These studies are part of a broad category termed two-phase studies. Common examples include the nested case-control and the case-cohort designs. For two-phase studies, appropriate weighted survival estimates have been derived; however, no estimator of cumulative incidence accounting for competing events has been proposed. This is relevant in the presence of multiple types of events, where estimation of event type specific quantities are needed for evaluating outcome. METHODS: We develop a non parametric estimator of the cumulative incidence function of events accounting for possible competing events. It handles a general sampling design by weights derived from the sampling probabilities. The variance is derived from the influence function of the subdistribution hazard. RESULTS: The proposed method shows good performance in simulations. It is applied to estimate the crude incidence of relapse in childhood acute lymphoblastic leukemia in groups defined by a genotype not available for everyone in a cohort of nearly 2000 patients, where death due to toxicity acted as a competing event. In a second example the aim was to estimate engagement in care of a cohort of HIV patients in resource limited setting, where for some patients the outcome itself was missing due to lost to follow-up. A sampling based approach was used to identify outcome in a subsample of lost patients and to obtain a valid estimate of connection to care. CONCLUSIONS: A valid estimator for cumulative incidence of events accounting for competing risks under a general sampling design from an infinite target population is derived.",2016 Jan 11,"['Rebora, Paola', 'Antolini, Laura', 'Glidden, David V.', 'Valsecchi, Maria Grazia']",BMC Med Res Methodol,,,True
e4e1a4d2d3384d9abc48576bb31cdb9c497732fb,PMC,Case–control study of pathogens involved in piglet diarrhea,http://dx.doi.org/10.1186/s13104-015-1751-2,PMC4710041,26754836,CC BY,"BACKGROUND: Diarrhea in piglets directly affects commercial swine production. The disease results from the interaction of pathogens with the host immune system and is also affected by management procedures. Several pathogenic agents such as Campylobacter spp., Clostridium perfringens, Escherichia coli, Salmonella spp., group A rotavirus (RV-A), coronaviruses (transmissible gastroenteritis virus; porcine epidemic diarrhea virus), as well as nematode and protozoan parasites, can be associated with disease cases. RESULTS: All bacterial, viral, protozoan, and parasitic agents here investigated, with the exception of Salmonella spp. as well as both coronaviruses, were detected in varying proportions in piglet fecal samples, and positive animals were equally distributed between case and control groups. A statistically significant difference between case and control groups was found only for Cystoisospora suis (p = 0.034) and Eimeria spp. (p = 0.047). When co-infections were evaluated, a statistically significant difference was found only for C. perfringens β2 and C. suis (p = 0.014). CONCLUSIONS: The presence of pathogens in piglets alone does not determine the occurrence of diarrhea episodes. Thus, the indiscriminate use of antibiotic and anthelminthic medication should be re-evaluated. This study also reinforces the importance of laboratory diagnosis and correct interpretation of results as well as the relevance of control and prophylactic measures.",2016 Jan 11,"['Ruiz, Vera L. A.', 'Bersano, Josete G.', 'Carvalho, Aline F.', 'Catroxo, Márcia H. B.', 'Chiebao, Daniela P.', 'Gregori, Fábio', 'Miyashiro, Simone', 'Nassar, Alessandra F. C.', 'Oliveira, Trícia M. F. S.', 'Ogata, Renato A.', 'Scarcelli, Eliana P.', 'Tonietti, Paloma O.']",BMC Res Notes,,,True
65731cfe4b5e1d05aa7c85d3b088346832c35315,PMC,Real-Time Reverse Transcription PCR Assay for Detection of Senecavirus A in Swine Vesicular Diagnostic Specimens,http://dx.doi.org/10.1371/journal.pone.0146211,PMC4710529,26757142,CC0,"Senecavirus A (SV-A), formerly, Seneca Valley virus (SVV), has been detected in swine with vesicular lesions and is thought to be associated with swine idiopathic vesicular disease (SIVD), a vesicular disease syndrome that lacks a defined causative agent. The clinical presentation of SIVD resembles that of other more contagious and economically devastating vesicular diseases, such as foot-and-mouth disease (FMD), swine vesicular disease (SVD), and vesicular stomatitis (VS), that typically require immediate rule out diagnostics to lift restrictions on animal quarantine, movement, and trade. This study presents the development of a sensitive, SYBR Green RT-qPCR assay suitable for detection of SV-A in diagnostic swine specimens. After testing 50 pigs with clinical signs consistent with vesicular disease, 44 (88%) were found to be positive for SV-A by RT-qPCR as compared to none from a negative cohort of 35 animals without vesicular disease, indicating that the assay is able to successfully detect the virus in an endemic population. SV-A RNA was also detectable at a low level in sera from a subset of pigs that presented with (18%) or without (6%) vesicular signs. In 2015, there has been an increase in the occurrence of SV-A in the US, and over 200 specimens submitted to our laboratory for vesicular investigation have tested positive for the virus using this method. SV-A RNA was detectable in all common types of vesicular specimens including swabs and tissue from hoof lesions, oral and snout epithelium, oral swabs, scabs, and internal organ tissues such as liver and lymph node. Genome sequencing analysis from recent virus isolates was performed to confirm target amplicon specificity and was aligned to previous isolates.",2016 Jan 12,"['Bracht, Alexa J.', 'O’Hearn, Emily S.', 'Fabian, Andrew W.', 'Barrette, Roger W.', 'Sayed, Abu']",PLoS One,,,True
8b17b1580dd61644c73c3c579212f45640cd107c,PMC,The leukocyte-stiffening property of plasma in early acute respiratory distress syndrome (ARDS) revealed by a microfluidic single-cell study: the role of cytokines and protection with antibodies,http://dx.doi.org/10.1186/s13054-015-1157-5,PMC4711060,26757701,CC BY,"BACKGROUND: Leukocyte-mediated pulmonary inflammation is a key pathophysiological mechanism involved in acute respiratory distress syndrome (ARDS). Massive sequestration of leukocytes in the pulmonary microvasculature is a major triggering event of the syndrome. We therefore investigated the potential role of leukocyte stiffness and adhesiveness in the sequestration of leukocytes in microvessels. METHODS: This study was based on in vitro microfluidic assays using patient sera. Cell stiffness was assessed by measuring the entry time (ET) of a single cell into a microchannel with a 6 × 9–μm cross-section under a constant pressure drop (ΔP = 160 Pa). Primary neutrophils and monocytes, as well as the monocytic THP-1 cell line, were used. Cellular adhesiveness to human umbilical vein endothelial cells was examined using the laminar flow chamber method. We compared the properties of cells incubated with the sera of healthy volunteers (n = 5), patients presenting with acute cardiogenic pulmonary edema (ACPE; n = 6), and patients with ARDS (n = 22), of whom 13 were classified as having moderate to severe disease and the remaining 9 as having mild disease. RESULTS: Rapid and strong stiffening of primary neutrophils and monocytes was induced within 30 minutes (mean ET >50 seconds) by sera from the ARDS group compared with both the healthy subjects and the ACPE groups (mean ET <1 second) (p < 0.05). Systematic measurements with the THP-1 cell line allowed for the establishment of a strong correlation between stiffening and the severity of respiratory status (mean ET 0.82 ± 0.08 seconds for healthy subjects, 1.6 ± 1.0 seconds for ACPE groups, 10.5 ± 6.1 seconds for mild ARDS, and 20.0 ± 8.1 seconds for moderate to severe ARDS; p < 0.05). Stiffening correlated with the cytokines interleukin IL-1β, IL-8, tumor necrosis factor TNF-α, and IL-10 but not with interferon-γ, transforming growth factor-β, IL-6, or IL-17. Strong stiffening was induced by IL-1β, IL-8, and TNF-α but not by IL-10, and incubations with sera and blocking antibodies against IL-1β, IL-8, or TNF-α significantly diminished the stiffening effect of serum. In contrast, the measurements of integrin expression (CD11b, CD11a, CD18, CD49d) and leukocyte–endothelium adhesion showed a weak and slow response after incubation with the sera of patients with ARDS (several hours), suggesting a lesser role of leukocyte adhesiveness compared with leukocyte stiffness in early ARDS. CONCLUSIONS: The leukocyte stiffening induced by cytokines in the sera of patients might play a role in the sequestration of leukocytes in the lung capillary beds during early ARDS. The inhibition of leukocyte stiffening with blocking antibodies might inspire future therapeutic strategies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-015-1157-5) contains supplementary material, which is available to authorized users.",2016 Jan 12,"['Preira, Pascal', 'Forel, Jean-Marie', 'Robert, Philippe', 'Nègre, Paulin', 'Biarnes-Pelicot, Martine', 'Xeridat, Francois', 'Bongrand, Pierre', 'Papazian, Laurent', 'Theodoly, Olivier']",Crit Care,,,True
1ccf19a7957dd88ddcce92605007ad16f26d28ed,PMC,Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger,http://dx.doi.org/10.1371/journal.ppat.1005373,PMC4711667,26730950,CC BY,"Ebola virus (EBOV) is a highly pathogenic filovirus that causes hemorrhagic fever in humans and animals. Currently, how EBOV fuses its envelope membrane within an endosomal membrane to cause infection is poorly understood. We successfully measure cell-cell fusion mediated by the EBOV fusion protein, GP, assayed by the transfer of both cytoplasmic and membrane dyes. A small molecule fusion inhibitor, a neutralizing antibody, as well as mutations in EBOV GP known to reduce viral infection, all greatly reduce fusion. By monitoring redistribution of small aqueous dyes between cells and by electrical capacitance measurements, we discovered that EBOV GP-mediated fusion pores do not readily enlarge—a marked difference from the behavior of other viral fusion proteins. EBOV GP must be cleaved by late endosome-resident cathepsins B or L in order to become fusion-competent. Cleavage of cell surface-expressed GP appears to occur in endosomes, as evidenced by the fusion block imposed by cathepsin inhibitors, agents that raise endosomal pH, or an inhibitor of anterograde trafficking. Treating effector cells with a recombinant soluble cathepsin B or thermolysin, which cleaves GP into an active form, increases the extent of fusion, suggesting that a fraction of surface-expressed GP is not cleaved. Whereas the rate of fusion is increased by a brief exposure to acidic pH, fusion does occur at neutral pH. Importantly, the extent of fusion is independent of external pH in experiments in which cathepsin activity is blocked and EBOV GP is cleaved by thermolysin. These results imply that low pH promotes fusion through the well-known pH-dependent activity of cathepsins; fusion induced by cleaved EBOV GP is a process that is fundamentally independent of pH. The cell-cell fusion system has revealed some previously unappreciated features of EBOV entry, which could not be readily elucidated in the context of endosomal entry.",2016 Jan 5,"['Markosyan, Ruben M.', 'Miao, Chunhui', 'Zheng, Yi-Min', 'Melikyan, Gregory B.', 'Liu, Shan-Lu', 'Cohen, Fredric S.']",PLoS Pathog,,,True
0304ed96b29c38014a17bacefcc294a02c04d0a0,PMC,Statistical Evaluation of HTS Assays for Enzymatic Hydrolysis of β-Keto Esters,http://dx.doi.org/10.1371/journal.pone.0146104,PMC4711668,26730596,CC BY,"β-keto esters are used as precursors for the synthesis of β-amino acids, which are building blocks for some classes of pharmaceuticals. Here we describe the comparison of screening procedures for hydrolases to be used for the hydrolysis of β-keto esters, the first step in the preparation of β-amino acids. Two of the tested high throughput screening (HTS) assays depend on coupled enzymatic reactions which detect the alcohol released during ester hydrolysis by luminescence or absorption. The third assay detects the pH shift due to acid formation using an indicator dye. To choose the most efficient approach for screening, we assessed these assays with different statistical methods—namely, the classical Z’-factor, standardized mean difference (SSMD), the Kolmogorov-Smirnov-test, and t-statistics. This revealed that all three assays are suitable for HTS, the pH assay performing best. Based on our data we discuss the explanatory power of different statistical measures. Finally, we successfully employed the pH assay to identify a very fast hydrolase in an enzyme-substrate screening.",2016 Jan 5,"['Buß, O.', 'Jager, S.', 'Dold, S. -M.', 'Zimmermann, S.', 'Hamacher, K.', 'Schmitz, K.', 'Rudat, J.']",PLoS One,,,True
a8adfbfaece0694336909eceb6fa3ed7e737ae9e,PMC,Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome,http://dx.doi.org/10.1371/journal.pone.0145694,PMC4712828,26745868,CC BY,"OBJECTIVE: It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. METHODS: Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAP(SB)) and abdominal muscle paralysis group (BIPAP(AP)). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH(2)O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO(2) of 35–60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment. RESULTS: For the comparable ventilator setting, as compared with BIPAP(SB) group, the BIPAP(AP) group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAP(AP) group (22.5±2.0 vs. 25.2±2.1). CONCLUSION: Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.",2016 Jan 8,"['Zhang, Xianming', 'Wu, Weiliang', 'Zhu, Yongcheng', 'Jiang, Ying', 'Du, Juan', 'Chen, Rongchang']",PLoS One,,,True
ad3ad574d436dbb8cb39de496b123c05588b3af9,PMC,Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome,http://dx.doi.org/10.1371/journal.pone.0145694,PMC4712828,26745868,CC BY,"OBJECTIVE: It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. METHODS: Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAP(SB)) and abdominal muscle paralysis group (BIPAP(AP)). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH(2)O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO(2) of 35–60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment. RESULTS: For the comparable ventilator setting, as compared with BIPAP(SB) group, the BIPAP(AP) group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAP(AP) group (22.5±2.0 vs. 25.2±2.1). CONCLUSION: Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.",2016 Jan 8,"['Zhang, Xianming', 'Wu, Weiliang', 'Zhu, Yongcheng', 'Jiang, Ying', 'Du, Juan', 'Chen, Rongchang']",PLoS One,,,False
360028f9b31d57ec6bbffa2c66602434f012f167,PMC,Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome,http://dx.doi.org/10.1371/journal.pone.0145694,PMC4712828,26745868,CC BY,"OBJECTIVE: It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. METHODS: Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAP(SB)) and abdominal muscle paralysis group (BIPAP(AP)). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH(2)O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO(2) of 35–60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment. RESULTS: For the comparable ventilator setting, as compared with BIPAP(SB) group, the BIPAP(AP) group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAP(AP) group (22.5±2.0 vs. 25.2±2.1). CONCLUSION: Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.",2016 Jan 8,"['Zhang, Xianming', 'Wu, Weiliang', 'Zhu, Yongcheng', 'Jiang, Ying', 'Du, Juan', 'Chen, Rongchang']",PLoS One,,,False
968d0b07b0b65a15cedfd2357e3ba9649742836e,PMC,Novel treatment of severe combined immunodeficiency utilizing ex-vivo T-cell depleted haploidentical hematopoietic stem cell transplantation and CD45RA+ depleted donor lymphocyte infusions,http://dx.doi.org/10.1186/s13023-016-0385-3,PMC4714422,26768987,CC BY,"BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment available for severe combined immunodeficiency (SCID); although, there is a high incidence of severe infections and an increased risk of graft-versus host-disease (GvHD) with HSCT. Early intervention is a crucial prognostic factor and a HLA-haploidentical parental donor is often available. Haploidentical HSCT protocols utilizing extensively ex vivo T-cell depleted grafts (CliniMACs system) have proven efficient in preventing GvHD, but cause a delay in early T-cell recovery that increases the risk of viral infections. Here, we present a novel approach for treating SCID that combines selective depletion of GvHD-inducing alpha/beta (α/β) T-cells from the haploidentical HSCT graft with a subsequent donor lymphocyte infusion (DLI) enriched for CD45RO+ memory T-cells. RESULTS: Our patient was diagnosed with SCID (T-B + NK+ phenotype). At 9 months of age, he received a T cell receptor(TCR)α/β-cell depleted graft from his haploidentical mother, following a reduced intensity conditioning regimen with no additional GvHD prophylaxis. Engraftment was rapid with complete donor chimerism and no signs of GvHD. However, at 12 weeks post HSCT, the patient was still T-cell lymphopenic with clinical symptoms of multiple severe viral infections. Consequently, therapeutic DLIs were initiated for enhanced anti-viral immunity. The patient was treated with CD45RA+ depleted haploidentical maternal donor lymphocytes enriched from unmobilized whole blood, and a total T-cell dose of no more than 25 x10(3) CD3+ cells/kg with >99.9 % purity of CD3 + CD45RO+ memory T-cells was transferred. Following the DLI, a prompt increase in CD3 + CD4+ and CD3 + CD8+ counts was observed with a subsequent clearance of viral infections. No acute or chronic GvHD was observed. CONCLUSIONS: Automated depletion of CD45RA+ naïve T-cells from unmobilized whole blood is a simple and rapid strategy to provide unmanipulated DLIs, with a potentially broad repertoire of pathogen specific memory T-cells. In the haploidentical setting, CD45RA+ depleted DLIs can be safely administered at low T-cell doses for efficient enhancement of viral immunity and limited risk of GvHD. We demonstrate the successful use of this approach following TCR-α/β-cell depleted HSCT for the treatment of SCID.",2016 Jan 15,"['Brodszki, Nicholas', 'Turkiewicz, Dominik', 'Toporski, Jacek', 'Truedsson, Lennart', 'Dykes, Josefina']",Orphanet J Rare Dis,,,True
0bf39c12d7c4576441079e2e758ec1eacfe015d1,PMC,Subcellular fractionation method to study endosomal trafficking of Kaposi’s sarcoma-associated herpesvirus,http://dx.doi.org/10.1186/s13578-015-0066-2,PMC4714431,26779333,CC BY,"BACKGROUND: Virus entry involves multiple steps and is a highly orchestrated process on which successful infection collectively depends. Entry processes are commonly analyzed by monitoring internalized virus particles via Western blotting, polymerase chain reaction, and imaging techniques that allow scientist to track the intracellular location of the pathogen. Such studies have provided abundant direct evidence on how viruses interact with receptor molecules on the cell surface, induce cell signaling at the point of initial contact with the cell to facilitate internalization, and exploit existing endocytic mechanisms of the cell for their ultimate infectious agenda. However, there is dearth of knowledge in regards to trafficking of a virus via endosomes. Herein, we describe an optimized laboratory procedure to isolate individual organelles during different stages of endocytosis by performing subcellular fractionation. This methodology is established using Kaposi’s sarcoma-associated herpesvirus (KSHV) infection of human foreskin fibroblast (HFF) cells as a model. With KSHV and other herpesviruses alike, envelope glycoproteins have been widely reported to physically engage target cell surface receptors, such as integrins, in interactions leading to entry and subsequent infection. RESULTS: Subcellular fractionation was used to isolate early and late endosomes (EEs and LEs) by performing a series of centrifugations steps. Specifically, a centrifugation step post-homogenization was utilized to obtain the post-nuclear supernatant containing intact intracellular organelles in suspension. Successive fractionation via sucrose density gradient centrifugation was performed to isolate specific organelles including EEs and LEs. Intracellular KSHV trafficking was directly traced in the isolated endosomal fractions. Additionally, the subcellular fractionation approach demonstrates a key role for integrins in the endosomal trafficking of KSHV. The results obtained from fractionation studies corroborated those obtained by traditional imaging studies. CONCLUSIONS: This study is the first of its kind to employ a sucrose flotation gradient assay to map intracellular KSHV trafficking in HFF cells. We are confident that such an approach will serve as a powerful tool to directly study intracellular trafficking of a virus, signaling events occurring on endosomal membranes, and dynamics of molecular events within endosomes that are crucial for uncoating and virus escape into the cytosol.",2016 Jan 15,"['Walker, Lia R.', 'Hussein, Hosni A. M.', 'Akula, Shaw M.']",Cell Biosci,,,True
4630378a0db8bae16b58ac19b512f9fffb0fc98f,PMC,Impact of Mated Female Nonproductive Days in Breeding Herd after Porcine Epidemic Diarrhea Virus Outbreak,http://dx.doi.org/10.1371/journal.pone.0147316,PMC4714882,26771383,CC BY,"Porcine epidemic diarrhea virus (PEDV) is an important pathogen that has a significant economic impact on the swine industry by imposing a high rate of mortality in suckling piglets. However, limited information on the productivity values of gilts and sows infected with PEDV is available. Here, we evaluate the productivity index in gilts and sows during the 1-year period before (19 January 2013 to 18 January 2014) and after (19 January 2014 to 18 January 2015) a PEDV outbreak from a 2000-sow breeding herd in Taiwan. The farrowing rate (FR), return rate (RR), total pigs born per litter (TB), pigs born alive per litter (BA), weaning pigs per litter (WPL), pre-weaning mortality, percentage of sows mated by 7 days after weaning, weaning to first service interval (WFSI), mated female nonproductive days (NPDs), replacement rate of sows and sow culling rate were compared using productive records. The FR (-9.6%), RR (+9.8%), TB (-1.6), BA (-1.1), WPL (-1.1), sows mated by 7 days after weaning (-6.9%), WFSI (+0.8 days), NPDs (+6.9 days) and sow culling rate (+7.2%) were significantly different between the 1-year pre-PEDV outbreak period and the post-PEDV outbreak period. Impacts of the PEDV infection on the reproductive performance were more severe in pregnant gilts than in sows. In conclusion, these findings indicate that the outbreak of PEDV caused an increase in the rate of NPDs in breeding herds.",2016 Jan 15,"['Lin, Jung-Da', 'Lin, Chuen-Fu', 'Chung, Wen-Bin', 'Chiou, Ming-Tang', 'Lin, Chao-Nan']",PLoS One,,,True
52babe7e5a33e5c40aab00ea9b3e0ff4a3dfa3ba,PMC,"Co-Circulation of Canine Coronavirus I and IIa/b with High Prevalence and Genetic Diversity in Heilongjiang Province, Northeast China",http://dx.doi.org/10.1371/journal.pone.0146975,PMC4714894,26771312,CC BY,"To trace the evolution of canine coronavirus (CCoV), 201 stool samples from diarrheic dogs in northeast China were subjected to reverse transcription-polymerase chain reactions (RT-PCRs) targeting the partial M and S genes of CCoV, followed by an epidemiological analysis. M gene RT-PCRs showed that 28.36% (57/201) of the samples were positive for CCoV; of the 57 positive samples, CCoV-I and CCoV-II accounted for 15.79% (9/57) and 84.21% (48/57), respectively. A sequence comparison of the partial M gene revealed nucleotide homologies of 88.4%–100% among the 57 CCoV strains, and 88.7%–96.2% identity between the 57 CCoV strains and the Chinese reference strain HF3. The CCoV-I and CCoV-II strains exhibited genetic diversity when compared with reference strains from China and other countries. The 57 CCoV strains exhibited high co-infection rates with canine kobuvirus (CaKV) (33.33%) and canine parvovirus-2 (CPV-2) (31.58%). The CCoV prevalence in diarrheic dogs differed significantly with immunization status, regions, seasons, and ages. Moreover, 28 S genes were amplified from the 57 CCoV-positive samples, including 26 CCoV-IIa strains, one CCoV-IIb strain, and one CCoV-I strain. A sequence comparison of the partial S gene revealed 86.3%–100% nucleotide identity among the 26 CCoV-IIa strains, and 89.6%–92.2% identity between the 26 CCoV-IIa strains and the Chinese reference strain V1. The 26 CCoV-IIa strains showed genetic diversity when compared with reference strains from China and other countries. Our data provide evidence that CCoV-I, CCoV-IIa, and CCoV-IIb strains co-circulate in the diarrhoetic dogs in northeast China, high co-infection rates with CaKV and CPV-2 were observed, and the CCoV-II strains exhibited high prevalence and genetic diversity.",2016 Jan 15,"['Wang, Xinyu', 'Li, Chunqiu', 'Guo, Donghua', 'Wang, Xinyu', 'Wei, Shan', 'Geng, Yufei', 'Wang, Enyu', 'Wang, Zhihui', 'Zhao, Xiwen', 'Su, Mingjun', 'Liu, Qiujin', 'Zhang, Siyao', 'Feng, Li', 'Sun, Dongbo']",PLoS One,,,True
8dd14ffdb898c891d284cff71623b3e43ec0b0fe,PMC,Absence of Middle East respiratory syndrome coronavirus in Bactrian camels in the West Inner Mongolia Autonomous Region of China: surveillance study results from July 2015,http://dx.doi.org/10.1038/emi.2015.73,PMC4715163,26632875,CC BY,,2015 Dec 2,"['Liu, Renqiang', 'Wen, Zhiyuan', 'Wang, Jinling', 'Ge, Jinying', 'Chen, Hualan', 'Bu, Zhigao']",Emerg Microbes Infect,,,True
3373c12fcd9f891217dec7833378f696637b6ddd,PMC,Fragments of Target Cells are Internalized into Retroviral Envelope Protein-Expressing Cells during Cell-Cell Fusion by Endocytosis,http://dx.doi.org/10.3389/fmicb.2015.01552,PMC4717186,26834711,CC BY,"Retroviruses enter into host cells by fusion between viral and host cell membranes. Retroviral envelope glycoprotein (Env) induces the membrane fusion, and also mediates cell-cell fusion. There are two types of cell-cell fusions induced by the Env protein. Fusion-from-within is induced by fusion between viral fusogenic Env protein-expressing cells and susceptible cells, and virions induce fusion-from-without by fusion between adjacent cells. Although entry of ecotropic murine leukemia virus (E-MLV) requires host cell endocytosis, the involvement of endocytosis in cell fusion is unclear. By fluorescent microscopic analysis of the fusion-from-within, we found that fragments of target cells are internalized into Env-expressing cells. Treatment of the Env-expressing cells with an endocytosis inhibitor more significantly inhibited the cell fusion than that of the target cells, indicating that endocytosis in Env-expressing cells is required for the cell fusion. The endocytosis inhibitor also attenuated the fusion-from-without. Electron microscopic analysis suggested that the membrane fusion resulting in fusion-from-within initiates in endocytic membrane dents. This study shows that two types of the viral cell fusion both require endocytosis, and provides the cascade of fusion-from-within.",2016 Jan 19,"['Izumida, Mai', 'Kamiyama, Haruka', 'Suematsu, Takashi', 'Honda, Eri', 'Koizumi, Yosuke', 'Yasui, Kiyoshi', 'Hayashi, Hideki', 'Ariyoshi, Koya', 'Kubo, Yoshinao']",Front Microbiol,,,True
b33f78304f8fdb97631ad4b5b5ed9d8d85d0622f,PMC,Endogenous adaptation to low oxygen modulates T-cell regulatory pathways in EAE,http://dx.doi.org/10.1186/s12974-015-0407-4,PMC4717549,26785841,CC BY,"BACKGROUND: In the brain, chronic inflammatory activity may lead to compromised delivery of oxygen and glucose suggesting that therapeutic approaches aimed at restoring metabolic balance may be useful. In vivo exposure to chronic mild normobaric hypoxia (10 % oxygen) leads to a number of endogenous adaptations that includes vascular remodeling (angioplasticity). Angioplasticity promotes tissue survival. We have previously shown that induction of adaptive angioplasticity modulates the disease pattern in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). In the present study, we define mechanisms by which adaptation to low oxygen functionally ameliorates the signs and symptoms of EAE and for the first time show that tissue hypoxia may fundamentally alter neurodegenerative disease. METHODS: C57BL/6 mice were immunized with MOG, and some of them were kept in the hypoxia chambers (day 0) and exposed to 10 % oxygen for 3 weeks, while the others were kept at normoxic environment. Sham-immunized controls were included in both hypoxic and normoxic groups. Animals were sacrificed at pre-clinical and peak disease periods for tissue collection and analysis. RESULTS: Exposure to mild hypoxia decreased histological evidence of inflammation. Decreased numbers of cluster of differentiation (CD)4+ T cells were found in the hypoxic spinal cords associated with a delayed Th17-specific cytokine response. Hypoxia-induced changes did not alter the sensitization of peripheral T cells to the MOG peptide. Exposure to mild hypoxia induced significant increases in anti-inflammatory IL-10 levels and an increase in the number of spinal cord CD25+FoxP3+ T-regulatory cells. CONCLUSIONS: Acclimatization to mild hypoxia incites a number of endogenous adaptations that induces an anti-inflammatory milieu. Further understanding of these mechanisms system may pinpoint possible new therapeutic targets to treat neurodegenerative disease.",2016 Jan 19,"['Esen, Nilufer', 'Katyshev, Vladimir', 'Serkin, Zakhar', 'Katysheva, Svetlana', 'Dore-Duffy, Paula']",J Neuroinflammation,,,True
faa8c6b399eff710bae62ce297e56c19fe212e74,PMC,Advancement and applications of peptide phage display technology in biomedical science,http://dx.doi.org/10.1186/s12929-016-0223-x,PMC4717660,26786672,CC BY,"Combinatorial phage library is a powerful research tool for high-throughput screening of protein interactions. Of all available molecular display techniques, phage display has proven to be the most popular approach. Screening phage-displayed random peptide libraries is an effective means of identifying peptides that can bind target molecules and regulate their function. Phage-displayed peptide libraries can be used for (i) B-cell and T-cell epitope mapping, (ii) selection of bioactive peptides bound to receptors or proteins, disease-specific antigen mimics, peptides bound to non-protein targets, cell-specific peptides, or organ-specific peptides, and (iii) development of peptide-mediated drug delivery systems and other applications. Targeting peptides identified using phage display technology may be useful for basic research and translational medicine. In this review article, we summarize the latest technological advancements in the application of phage-displayed peptide libraries to applied biomedical sciences.",2016 Jan 19,"['Wu, Chien-Hsun', 'Liu, I-Ju', 'Lu, Ruei-Min', 'Wu, Han-Chung']",J Biomed Sci,,,True
5483fa35c312dcdefe0216e85fcbdafec45cf84e,PMC,Evolution of research in health geographics through the International Journal of Health Geographics (2002–2015),http://dx.doi.org/10.1186/s12942-016-0032-1,PMC4719657,26790403,CC BY,"Health geographics is a fast-developing research area. Subjects broached in scientific literature are most varied, ranging from vectorial diseases to access to healthcare, with a recent revival of themes such as the implication of health in the Smart City, or a predominantly individual-centered approach. Far beyond standard meta-analyses, the present study deliberately adopts the standpoint of questioning space in its foundations, through various authors of the International Journal of Health Geographics, a highly influential journal in that field. The idea is to find space as the common denominator in this specialized literature, as well as its relation to spatial analysis, without for all that trying to tend towards exhaustive approaches. 660 articles have being published in the journal since launch, but 359 articles were selected based on the presence of the word “Space” in either the title, or the abstract or the text over 13 years of the journal’s existence. From that database, a lexical analysis (tag cloud) reveals the perception of space in literature, and shows how approaches are evolving, thus underlining that the scope of health geographics is far from narrowing.",2016 Jan 20,"['Pérez, Sandra', 'Laperrière, Vincent', 'Borderon, Marion', 'Padilla, Cindy', 'Maignant, Gilles', 'Oliveau, Sébastien']",Int J Health Geogr,,,True
efd27ff0ac04dd60838266386aaebb5df80f4fa9,PMC,Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus,http://dx.doi.org/10.1371/journal.pone.0147041,PMC4720120,26761647,CC BY,"In order to improve clinical management and prevention of viral infections in hospitalised children improved etiological insight is needed. The aim of the present study was to assess the spectrum of respiratory viral pathogens in children admitted to hospital with acute respiratory tract infections in Cyprus. For this purpose nasopharyngeal swab samples from 424 children less than 12 years of age with acute respiratory tract infections were collected over three epidemic seasons and were analysed for the presence of the most common 15 respiratory viruses. A viral pathogen was identified in 86% of the samples, with multiple infections being observed in almost 20% of the samples. The most frequently detected viruses were RSV (30.4%) and Rhinovirus (27.4%). RSV exhibited a clear seasonality with marked peaks in January/February, while rhinovirus infections did not exhibit a pronounced seasonality being detected almost throughout the year. While RSV and PIV3 incidence decreased significantly with age, the opposite was observed for influenza A and B as well as adenovirus infections. The data presented expand our understanding of the epidemiology of viral respiratory tract infections in Cypriot children and will be helpful to the clinicians and researchers interested in the treatment and control of viral respiratory tract infections.",2016 Jan 13,"['Richter, Jan', 'Panayiotou, Christakis', 'Tryfonos, Christina', 'Koptides, Dana', 'Koliou, Maria', 'Kalogirou, Nikolas', 'Georgiou, Eleni', 'Christodoulou, Christina']",PLoS One,,,True
1acdf5e9f35557c6fc3c102e865354a6b2359bc3,PMC,Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus,http://dx.doi.org/10.1371/journal.pone.0147041,PMC4720120,26761647,CC BY,"In order to improve clinical management and prevention of viral infections in hospitalised children improved etiological insight is needed. The aim of the present study was to assess the spectrum of respiratory viral pathogens in children admitted to hospital with acute respiratory tract infections in Cyprus. For this purpose nasopharyngeal swab samples from 424 children less than 12 years of age with acute respiratory tract infections were collected over three epidemic seasons and were analysed for the presence of the most common 15 respiratory viruses. A viral pathogen was identified in 86% of the samples, with multiple infections being observed in almost 20% of the samples. The most frequently detected viruses were RSV (30.4%) and Rhinovirus (27.4%). RSV exhibited a clear seasonality with marked peaks in January/February, while rhinovirus infections did not exhibit a pronounced seasonality being detected almost throughout the year. While RSV and PIV3 incidence decreased significantly with age, the opposite was observed for influenza A and B as well as adenovirus infections. The data presented expand our understanding of the epidemiology of viral respiratory tract infections in Cypriot children and will be helpful to the clinicians and researchers interested in the treatment and control of viral respiratory tract infections.",2016 Jan 13,"['Richter, Jan', 'Panayiotou, Christakis', 'Tryfonos, Christina', 'Koptides, Dana', 'Koliou, Maria', 'Kalogirou, Nikolas', 'Georgiou, Eleni', 'Christodoulou, Christina']",PLoS One,,,False
7a5a7445e0af990d098dbad733a408edc32642ae,PMC,Middle East Respiratory Syndrome Coronavirus Intra-Host Populations Are Characterized by Numerous High Frequency Variants,http://dx.doi.org/10.1371/journal.pone.0146251,PMC4720378,26790002,CC0,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging human pathogen related to SARS virus. In vitro studies indicate this virus may have a broad host range suggesting an increased pandemic potential. Genetic and epidemiological evidence indicate camels serve as a reservoir for MERS virus but the mechanism of cross species transmission is unclear and many questions remain regarding the susceptibility of humans to infection. Deep sequencing data was obtained from the nasal samples of three camels that had been experimentally infected with a human MERS-CoV isolate. A majority of the genome was covered and average coverage was greater than 12,000x depth. Although only 5 mutations were detected in the consensus sequences, 473 intrahost single nucleotide variants were identified. Many of these variants were present at high frequencies and could potentially influence viral phenotype and the sensitivity of detection assays that target these regions for primer or probe binding.",2016 Jan 20,"['Borucki, Monica K.', 'Lao, Victoria', 'Hwang, Mona', 'Gardner, Shea', 'Adney, Danielle', 'Munster, Vincent', 'Bowen, Richard', 'Allen, Jonathan E.']",PLoS One,,,True
91af77e42a7599eda8f4d061e0261dc39b092df6,PMC,Middle East Respiratory Syndrome Coronavirus Intra-Host Populations Are Characterized by Numerous High Frequency Variants,http://dx.doi.org/10.1371/journal.pone.0146251,PMC4720378,26790002,CC0,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging human pathogen related to SARS virus. In vitro studies indicate this virus may have a broad host range suggesting an increased pandemic potential. Genetic and epidemiological evidence indicate camels serve as a reservoir for MERS virus but the mechanism of cross species transmission is unclear and many questions remain regarding the susceptibility of humans to infection. Deep sequencing data was obtained from the nasal samples of three camels that had been experimentally infected with a human MERS-CoV isolate. A majority of the genome was covered and average coverage was greater than 12,000x depth. Although only 5 mutations were detected in the consensus sequences, 473 intrahost single nucleotide variants were identified. Many of these variants were present at high frequencies and could potentially influence viral phenotype and the sensitivity of detection assays that target these regions for primer or probe binding.",2016 Jan 20,"['Borucki, Monica K.', 'Lao, Victoria', 'Hwang, Mona', 'Gardner, Shea', 'Adney, Danielle', 'Munster, Vincent', 'Bowen, Richard', 'Allen, Jonathan E.']",PLoS One,,,False
9acdb5b67128d1cf69d690e4a340f2c961ce778d,PMC,Middle East Respiratory Syndrome Coronavirus Intra-Host Populations Are Characterized by Numerous High Frequency Variants,http://dx.doi.org/10.1371/journal.pone.0146251,PMC4720378,26790002,CC0,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging human pathogen related to SARS virus. In vitro studies indicate this virus may have a broad host range suggesting an increased pandemic potential. Genetic and epidemiological evidence indicate camels serve as a reservoir for MERS virus but the mechanism of cross species transmission is unclear and many questions remain regarding the susceptibility of humans to infection. Deep sequencing data was obtained from the nasal samples of three camels that had been experimentally infected with a human MERS-CoV isolate. A majority of the genome was covered and average coverage was greater than 12,000x depth. Although only 5 mutations were detected in the consensus sequences, 473 intrahost single nucleotide variants were identified. Many of these variants were present at high frequencies and could potentially influence viral phenotype and the sensitivity of detection assays that target these regions for primer or probe binding.",2016 Jan 20,"['Borucki, Monica K.', 'Lao, Victoria', 'Hwang, Mona', 'Gardner, Shea', 'Adney, Danielle', 'Munster, Vincent', 'Bowen, Richard', 'Allen, Jonathan E.']",PLoS One,,,False
2bd4bc16d5673b6c0de2e4283abd461b43e45a64,PMC,Middle East Respiratory Syndrome Coronavirus Intra-Host Populations Are Characterized by Numerous High Frequency Variants,http://dx.doi.org/10.1371/journal.pone.0146251,PMC4720378,26790002,CC0,"Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging human pathogen related to SARS virus. In vitro studies indicate this virus may have a broad host range suggesting an increased pandemic potential. Genetic and epidemiological evidence indicate camels serve as a reservoir for MERS virus but the mechanism of cross species transmission is unclear and many questions remain regarding the susceptibility of humans to infection. Deep sequencing data was obtained from the nasal samples of three camels that had been experimentally infected with a human MERS-CoV isolate. A majority of the genome was covered and average coverage was greater than 12,000x depth. Although only 5 mutations were detected in the consensus sequences, 473 intrahost single nucleotide variants were identified. Many of these variants were present at high frequencies and could potentially influence viral phenotype and the sensitivity of detection assays that target these regions for primer or probe binding.",2016 Jan 20,"['Borucki, Monica K.', 'Lao, Victoria', 'Hwang, Mona', 'Gardner, Shea', 'Adney, Danielle', 'Munster, Vincent', 'Bowen, Richard', 'Allen, Jonathan E.']",PLoS One,,,False
eb6e2ba036db0dcd7515f6c8b74938e89201b8ab,PMC,Nucleoprotein of influenza A virus negatively impacts antiapoptotic protein API5 to enhance E2F1-dependent apoptosis and virus replication,http://dx.doi.org/10.1038/cddis.2015.360,PMC4720893,26673663,CC BY,"Apoptosis of host cells profoundly influences virus propagation and dissemination, events that are integral to influenza A virus (IAV) pathogenesis. The trigger for activation of apoptosis is regulated by an intricate interplay between cellular and viral proteins, with a strong bearing on IAV replication. Though the knowledge of viral proteins and mechanisms employed by IAV to induce apoptosis has advanced considerably of late, we know relatively little about the repertoire of host factors targeted by viral proteins. Thus, identification of cellular proteins that are hijacked by the virus will help us not only to understand the molecular underpinnings of IAV-induced apoptosis, but also to design future antiviral therapies. Here we show that the nucleoprotein (NP) of IAV directly interacts with and suppresses the expression of API5, a host antiapoptotic protein that antagonizes E2F1-dependent apoptosis. siRNA-mediated depletion of API5, in NP-overexpressed as well as IAV-infected cells, leads to upregulation of apoptotic protease activating factor 1 (APAF1), a downstream modulator of E2F1-mediated apoptosis, and cleavage of caspases 9 and 3, although a reciprocal pattern of these events was observed on ectopic overexpression of API5. In concordance with these observations, annexin V and 7AAD staining assays exhibit downregulation of early and late apoptosis in IAV-infected or NP-transfected cells on overexpression of API5. Most significantly, while overexpression of API5 decreases viral titers, cellular NP protein as well as mRNA levels in IAV-infected A549 cells, silencing of API5 expression causes a steep rise in the same parameters. From the data reported in this manuscript, we propose a proapoptotic role for NP in IAV pathogenesis, whereby it suppresses expression of antiapoptotic factor API5, thus potentiating the E2F1-dependent apoptotic pathway and ensuring viral replication.",2015 Dec 17,"['Mayank, A K', 'Sharma, S', 'Nailwal, H', 'Lal, S K']",Cell Death Dis,,,True
f1d92c740ecb6d711507ed6e483472c8e1ecb3a6,PMC,One health – an ecological and evolutionary framework for tackling Neglected Zoonotic Diseases,http://dx.doi.org/10.1111/eva.12341,PMC4721077,26834828,CC BY,"Understanding the complex population biology and transmission ecology of multihost parasites has been declared as one of the major challenges of biomedical sciences for the 21st century and the Neglected Zoonotic Diseases (NZDs) are perhaps the most neglected of all the Neglected Tropical Diseases (NTDs). Here we consider how multihost parasite transmission and evolutionary dynamics may affect the success of human and animal disease control programmes, particularly neglected diseases of the developing world. We review the different types of zoonotic interactions that occur, both ecological and evolutionary, their potential relevance for current human control activities, and make suggestions for the development of an empirical evidence base and theoretical framework to better understand and predict the outcome of such interactions. In particular, we consider whether preventive chemotherapy, the current mainstay of NTD control, can be successful without a One Health approach. Transmission within and between animal reservoirs and humans can have important ecological and evolutionary consequences, driving the evolution and establishment of drug resistance, as well as providing selective pressures for spill‐over, host switching, hybridizations and introgressions between animal and human parasites. Our aim here is to highlight the importance of both elucidating disease ecology, including identifying key hosts and tailoring control effort accordingly, and understanding parasite evolution, such as precisely how infectious agents may respond and adapt to anthropogenic change. Both elements are essential if we are to alleviate disease risks from NZDs in humans, domestic animals and wildlife.",2016 Jan 8,"['Webster, Joanne P.', 'Gower, Charlotte M.', 'Knowles, Sarah C. L.', 'Molyneux, David H.', 'Fenton, Andy']",Evol Appl,,,True
4a074382e2fd63f0f5e882c0014e1e07d61c286a,PMC,Recent advances in biosynthesis of bioactive compounds in traditional Chinese medicinal plants,http://dx.doi.org/10.1007/s11434-015-0929-2,PMC4722072,26844006,CC BY,"Plants synthesize and accumulate large amount of specialized (or secondary) metabolites also known as natural products, which provide a rich source for modern pharmacy. In China, plants have been used in traditional medicine for thousands of years. Recent development of molecular biology, genomics and functional genomics as well as high-throughput analytical chemical technologies has greatly promoted the research on medicinal plants. In this article, we review recent advances in the elucidation of biosynthesis of specialized metabolites in medicinal plants, including phenylpropanoids, terpenoids and alkaloids. These natural products may share a common upstream pathway to form a limited numbers of common precursors, but are characteristic in distinct modifications leading to highly variable structures. Although this review is focused on traditional Chinese medicine, other plants with a great medicinal interest or potential are also discussed. Understanding of their biosynthesis processes is critical for producing these highly value molecules at large scale and low cost in microbes and will benefit to not only human health but also plant resource conservation.",2016 Nov 2,"['Yang, Lei', 'Yang, Changqing', 'Li, Chenyi', 'Zhao, Qing', 'Liu, Ling', 'Fang, Xin', 'Chen, Xiao-Ya']",Sci Bull (Beijing),,,True
3ed1483725e4ea6abcdbf93585eeccde903202fd,PMC,The first case of the 2015 Korean Middle East Respiratory Syndrome outbreak,http://dx.doi.org/10.4178/epih/e2015049,PMC4722220,26725226,CC BY,"This study reviewed problems in the prevention of outbreak and spread of Middle East Respiratory Syndrome (MERS) and aimed to provide assistance in establishing policies to prevent and manage future outbreaks of novel infectious diseases of foreign origin via in-depth epidemiological investigation of the patient who initiated the MERS outbreak in Korea, 2015. Personal and phone interviews were conducted with the patient and his guardians, and his activities in Saudi Arabia were investigated with the help of the Saudi Arabian Ministry of Health. Clinical courses and test results were confirmed from the medical records. The patient visited 4 medical facilities and contacted 742 people between May 11, 2015, at symptom onset, and May 20, at admission to the National Medical Center; 28 people were infected and diagnosed with MERS thereafter. Valuable lessons learned included: (1) epidemiological knowledge on the MERS transmission pattern and medical knowledge on its clinical course; (2) improvement of epidemiological investigative methods via closed-circuit television, global positioning system tracking, and review of Health Insurance Review and Assessment Service records; (3) problems revealed in the existing preventive techniques, including early determination of the various people contacted; (4) experiences with preventive methods used for the first time in Korea, including cohort quarantine; (5) reconsideration of the management systems for infectious disease outbreaks across the country, such as this case, at the levels of central government, local government, and the public; (6) reconsideration of hospital infectious disease management systems, culture involving patient visitation, and emergency room environments.",2015 Nov 14,"['Park, Yong-Shik', 'Lee, Changhwan', 'Kim, Kyung Min', 'Kim, Seung Woo', 'Lee, Keon-Joo', 'Ahn, Jungmo', 'Ki, Moran']",Epidemiol Health,,,True
5d96b673ebcceaca3fbfedc78675fed62c2bf8d9,PMC,The first case of the 2015 Korean Middle East Respiratory Syndrome outbreak,http://dx.doi.org/10.4178/epih/e2015049,PMC4722220,26725226,CC BY,"This study reviewed problems in the prevention of outbreak and spread of Middle East Respiratory Syndrome (MERS) and aimed to provide assistance in establishing policies to prevent and manage future outbreaks of novel infectious diseases of foreign origin via in-depth epidemiological investigation of the patient who initiated the MERS outbreak in Korea, 2015. Personal and phone interviews were conducted with the patient and his guardians, and his activities in Saudi Arabia were investigated with the help of the Saudi Arabian Ministry of Health. Clinical courses and test results were confirmed from the medical records. The patient visited 4 medical facilities and contacted 742 people between May 11, 2015, at symptom onset, and May 20, at admission to the National Medical Center; 28 people were infected and diagnosed with MERS thereafter. Valuable lessons learned included: (1) epidemiological knowledge on the MERS transmission pattern and medical knowledge on its clinical course; (2) improvement of epidemiological investigative methods via closed-circuit television, global positioning system tracking, and review of Health Insurance Review and Assessment Service records; (3) problems revealed in the existing preventive techniques, including early determination of the various people contacted; (4) experiences with preventive methods used for the first time in Korea, including cohort quarantine; (5) reconsideration of the management systems for infectious disease outbreaks across the country, such as this case, at the levels of central government, local government, and the public; (6) reconsideration of hospital infectious disease management systems, culture involving patient visitation, and emergency room environments.",2015 Nov 14,"['Park, Yong-Shik', 'Lee, Changhwan', 'Kim, Kyung Min', 'Kim, Seung Woo', 'Lee, Keon-Joo', 'Ahn, Jungmo', 'Ki, Moran']",Epidemiol Health,,,False
da44bf992234002dde4e9301581944911e58a633,PMC,"Lessons learned from new emerging infectious disease, Middle East Respiratory Syndrome coronavirus outbreak in Korea",http://dx.doi.org/10.4178/epih/e2015051,PMC4722224,26725227,CC BY,,2015 Nov 17,"Kim, Joung Soon",Epidemiol Health,,,False
293bebb82f2e4687a1d257e75483a2e150de41b1,PMC,"Lessons learned from new emerging infectious disease, Middle East Respiratory Syndrome coronavirus outbreak in Korea",http://dx.doi.org/10.4178/epih/e2015051,PMC4722224,26725227,CC BY,,2015 Nov 17,"Kim, Joung Soon",Epidemiol Health,,,False
634b79269e0f00d35bcea1a2dc7643884b8c6b3a,PMC,Surface vimentin is critical for the cell entry of SARS-CoV,http://dx.doi.org/10.1186/s12929-016-0234-7,PMC4724099,26801988,CC BY,"BACKGROUND: Severe acute respiratory syndrome coronavirus (SARS-CoV) caused a global panic due to its high morbidity and mortality during 2002 and 2003. Soon after the deadly disease outbreak, the angiotensin-converting enzyme 2 (ACE2) was identified as a functional cellular receptor in vitro and in vivo for SARS-CoV spike protein. However, ACE2 solely is not sufficient to allow host cells to become susceptible to SARS-CoV infection, and other host factors may be involved in SARS-CoV spike protein-ACE2 complex. RESULTS: A host intracellular filamentous cytoskeletal protein vimentin was identified by immunoprecipitation and LC-MS/MS analysis following chemical cross-linking on Vero E6 cells that were pre-incubated with the SARS-CoV spike protein. Moreover, flow cytometry data demonstrated an increase of the cell surface vimentin level by 16.5 % after SARS-CoV permissive Vero E6 cells were treated with SARS-CoV virus-like particles (VLPs). A direct interaction between SARS-CoV spike protein and host surface vimentin was further confirmed by far-Western blotting. In addition, antibody neutralization assay and shRNA knockdown experiments indicated a vital role of vimentin in cell binding and uptake of SARS-CoV VLPs and the viral spike protein. CONCLUSIONS: A direct interaction between vimentin and SARS-CoV spike protein during viral entry was observed. Vimentin is a putative anti-viral drug target for preventing/reducing the susceptibility to SARS-CoV infection.",2016 Jan 22,"['Yu, Yvonne Ting-Chun', 'Chien, Ssu-Chia', 'Chen, I-Yin', 'Lai, Chia-Tsen', 'Tsay, Yeou-Guang', 'Chang, Shin C.', 'Chang, Ming-Fu']",J Biomed Sci,,,True
4878d966944fb0b66d96fec7b7dff3f79194f26d,PMC,Endocytic function is critical for influenza A virus infection via DC-SIGN and L-SIGN,http://dx.doi.org/10.1038/srep19428,PMC4725901,26763587,CC BY,"The ubiquitous presence of cell-surface sialic acid (SIA) has complicated efforts to identify specific transmembrane glycoproteins that function as bone fide entry receptors for influenza A virus (IAV) infection. The C-type lectin receptors (CLRs) DC-SIGN (CD209) and L-SIGN (CD209L) enhance IAV infection however it is not known if they act as attachment factors, passing virions to other unknown receptors for virus entry, or as authentic entry receptors for CLR-mediated virus uptake and infection. Sialic acid-deficient Lec2 Chinese Hamster Ovary (CHO) cell lines were resistant to IAV infection whereas expression of DC-SIGN/L-SIGN restored susceptibility of Lec2 cells to pH- and dynamin-dependent infection. Moreover, Lec2 cells expressing endocytosis-defective DC-SIGN/L-SIGN retained capacity to bind IAV but showed reduced susceptibility to infection. These studies confirm that DC-SIGN and L-SIGN are authentic endocytic receptors for IAV entry and infection.",2016 Jan 14,"['Gillespie, Leah', 'Roosendahl, Paula', 'Ng, Wy Ching', 'Brooks, Andrew G.', 'Reading, Patrick C.', 'Londrigan, Sarah L.']",Sci Rep,,,True
abb5a68caf42d65dcb946056258028cccf87cd4a,PMC,A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus,http://dx.doi.org/10.1038/srep19176,PMC4726036,26777545,CC BY,"Virus evolves rapidly to escape vaccine-induced immunity, posing a desperate demand for efficient vaccine development biotechnologies. Here we present an express vaccine development strategy based on CRISPR/Cas9 and Cre/Lox system against re-emerging Pseudorabies virus, which caused the recent devastating swine pseudorabies outbreak in China. By CRISPR/Cas9 system, the virulent genes of the newly isolated strain were simultaneously substituted by marker genes, which were subsequently excised using Cre/Lox system for vaccine safety concern. Notably, single cell FACS technology was applied to further promote virus purification efficiency. The combination of these state-of-art technologies greatly accelerated vaccine development. Finally, vaccination and challenge experiments proved this vaccine candidate’s protective efficacy in pigs and the promise to control current pseudorabies outbreak. This is, to our knowledge, the first successful vaccine development based on gene edit technologies, demonstrating these technologies leap from laboratory to industry. It may pave the way for future express antiviral vaccine development.",2016 Jan 18,"['Liang, Xun', 'Sun, Leqiang', 'Yu, Teng', 'Pan, Yongfei', 'Wang, Dongdong', 'Hu, Xueying', 'Fu, Zhenfang', 'He, Qigai', 'Cao, Gang']",Sci Rep,,,True
3240a95510e3a28cf3215c72090000c3458ca8db,PMC,A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus,http://dx.doi.org/10.1038/srep19176,PMC4726036,26777545,CC BY,"Virus evolves rapidly to escape vaccine-induced immunity, posing a desperate demand for efficient vaccine development biotechnologies. Here we present an express vaccine development strategy based on CRISPR/Cas9 and Cre/Lox system against re-emerging Pseudorabies virus, which caused the recent devastating swine pseudorabies outbreak in China. By CRISPR/Cas9 system, the virulent genes of the newly isolated strain were simultaneously substituted by marker genes, which were subsequently excised using Cre/Lox system for vaccine safety concern. Notably, single cell FACS technology was applied to further promote virus purification efficiency. The combination of these state-of-art technologies greatly accelerated vaccine development. Finally, vaccination and challenge experiments proved this vaccine candidate’s protective efficacy in pigs and the promise to control current pseudorabies outbreak. This is, to our knowledge, the first successful vaccine development based on gene edit technologies, demonstrating these technologies leap from laboratory to industry. It may pave the way for future express antiviral vaccine development.",2016 Jan 18,"['Liang, Xun', 'Sun, Leqiang', 'Yu, Teng', 'Pan, Yongfei', 'Wang, Dongdong', 'Hu, Xueying', 'Fu, Zhenfang', 'He, Qigai', 'Cao, Gang']",Sci Rep,,,False
55248fb2e12f9712b35a26e3fdb723baea0ac775,PMC,Genomic Motifs as a Novel Indicator of the Relationship between Strains Isolated from the Epidemic of Porcine Epidemic Diarrhea in 2013-2014,http://dx.doi.org/10.1371/journal.pone.0147994,PMC4726493,26808527,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a positive-sense RNA virus that causes infectious gastroenteritis in pigs. Following a PED outbreak that occurred in China in 2010, the disease was identified for the first time in the United States in April 2013, and was reported in many other countries worldwide from 2013 to 2014. As a novel approach to elucidate the epidemiological relationship between PEDV strains, we explored their genome sequences to identify the motifs that were shared within related strains. Of PED outbreaks reported in many countries during 2013–2014, 119 PEDV strains in Japan, USA, Canada, Mexico, Germany, and Korea were selected and used in this study. We developed a motif mining program, which aimed to identify a specific region of the genome that was exclusively shared by a group of PEDV strains. Eight motifs were identified (M1–M8) and they were observed in 41, 9, 18, 6, 10, 14, 2, and 2 strains, respectively. Motifs M1–M6 were shared by strains from more than two countries, and seemed to originate from one PEDV strain, Indiana12.83/USA/2013, among the 119 strains studied. BLAST search for motifs M1–M6 revealed that M3–M5 were almost identical to the strain ZMDZY identified in 2011 in China, while M1 and M2 were similar to other Chinese strains isolated in 2011–2012. Consequently, the PED outbreaks in these six countries may be closely related, and multiple transmissions of PEDV strains between these countries may have occurred during 2013–2014. Although tools such as phylogenetic tree analysis with whole genome sequences are increasingly applied to reveal the connection between isolates, its interpretation is sometimes inconclusive. Application of motifs as a tool to examine the whole genome sequences of causative agents will be more objective and will be an explicit indicator of their relationship.",2016 Jan 25,"['Yamamoto, Takehisa', 'Suzuki, Tohru', 'Ohashi, Seiichi', 'Miyazaki, Ayako', 'Tsutsui, Toshiyuki']",PLoS One,,,True
17d4c1e70195453379ed6529851c51d204fdc926,PMC,Bovine respiratory syncytial virus outbreak reduced bulls’ weight gain and feed conversion for eight months in a Norwegian beef herd,http://dx.doi.org/10.1186/s13028-016-0190-y,PMC4727385,26810215,CC BY,"BACKGROUND: Cost-benefit evaluation of measures against respiratory disease in cattle requires accounting with the associated production losses. Investigations of naturally occurring respiratory infections in a herd setting are an opportunity for accurate estimates of the consequences. This article presents estimates based on individual monitoring of weight and concentrate intake of several hundred bulls previous to, during and after a respiratory infection outbreak with bovine respiratory syncytial virus (BRSV) as the main pathogen. The aim of the study was to analyse the association between exposure to BRSV, weight gain and feed conversion rate, quantify any change in these parameters, and estimate the duration of the change in production. RESULTS: A comparison of growth curves for the bulls that were present during the outbreak revealed that bulls with severe clinical signs had a clear and consistent trend of poorer growth rate than those with milder or no signs. The weight/age-ratio was 0.04–0.10 lower in the severely affected bulls, and evident throughout the study period of 8 months. A comparison of growth rates between apparently healthy bulls being present during the outbreak and a comparable group of bulls exactly 1 year later (n = 377) showed a reduced growth rate of 111 g/day in the first group. The difference amounted to 23 extra days needed to reach the reference weight. Feed conversion was also reduced by 79 g weight gain/kilogram concentrate consumed in the outbreak year. CONCLUSION: This study indicates significant negative effects on performance of animals that develop severe clinical signs in the acute stage, and that the growth and production is negatively affected many months after apparent recovery. In addition, the performance of apparently healthy animals that are exposed during an outbreak are severely negatively affected. The duration of this decrease in production in animals after recovery, or animals that have not shown disease at all, has not previously been documented. These losses will easily be underestimated, but contribute significantly to the costs for the producer. The findings emphasize the importance of BRSV infection for profitability and animal welfare in cattle husbandry. The study also illustrates that utilising intra-herd comparison of health and production parameters is a productive approach to estimate consequences of an outbreak.",2016 Jan 25,"['Klem, Thea Blystad', 'Kjæstad, Hans Petter', 'Kummen, Eiliv', 'Holen, Hallstein', 'Stokstad, Maria']",Acta Vet Scand,,,True
39855ca915f908855de8577baf009e5b1acf5f5c,PMC,Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus,http://dx.doi.org/10.1038/srep19840,PMC4728398,26813885,CC BY,"Respiratory syncytial virus (RSV) infection is a major cause of severe lower respiratory illness in infants and young children, but the underlying mechanisms responsible for viral pathogenesis have not been fully elucidated. To date, no drugs or vaccines have been employed to improve clinical outcomes for RSV-infected patients. In this paper, we report that angiotensin-converting enzyme-2 (ACE2) protected against severe lung injury induced by RSV infection in an experimental mouse model and in pediatric patients. Moreover, ACE2 deficiency aggravated RSV-associated disease pathogenesis, mainly by its action on the angiotensin II type 1 receptor (AT1R). Furthermore, administration of a recombinant ACE2 protein alleviated the severity of RSV-induced lung injury. These findings demonstrate that ACE2 plays a critical role in preventing RSV-induced lung injury, and suggest that ACE2 is a promising potential therapeutic target in the management of RSV-induced lung disease.",2016 Jan 27,"['Gu, Hongjing', 'Xie, Zhengde', 'Li, Tieling', 'Zhang, Shaogeng', 'Lai, Chengcai', 'Zhu, Ping', 'Wang, Keyu', 'Han, Lina', 'Duan, Yueqiang', 'Zhao, Zhongpeng', 'Yang, Xiaolan', 'Xing, Li', 'Zhang, Peirui', 'Wang, Zhouhai', 'Li, Ruisheng', 'Yu, Jane J.', 'Wang, Xiliang', 'Yang, Penghui']",Sci Rep,,,True
63a98dbb196b0ceacae4a16715ca8540b857cd22,PMC,Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry,http://dx.doi.org/10.3390/v8010006,PMC4728566,26712783,CC BY,"Influenza A viruses (IAVs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-IAV agents. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. Here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) with half maximal inhibitory concentration (IC(50)) of 7.756 ± 1.097, 6.225 ± 0.467, and 2.738 ± 1.931 μg/mL, respectively. Mechanism studies identified that quercetin showed interaction with the HA2 subunit. Moreover, quercetin could inhibit the entry of the H5N1 virus using the pseudovirus-based drug screening system. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of IAV infections.",2015 Dec 25,"['Wu, Wenjiao', 'Li, Richan', 'Li, Xianglian', 'He, Jian', 'Jiang, Shibo', 'Liu, Shuwen', 'Yang, Jie']",Viruses,,,True
df605c7743673dade86350172a3c6513bc437c90,PMC,Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC,http://dx.doi.org/10.3390/v8010016,PMC4728576,26761027,CC BY,"Rhinoviruses (RVs) and respiratory enteroviruses (EVs) are leading causes of upper respiratory tract infections and among the most frequent infectious agents in humans worldwide. Both are classified in the Enterovirus genus within the Picornaviridae family and they have been assigned to seven distinct species, RV-A, B, C and EV-A, B, C, D. As viral infections of public health significance, they represent an important financial burden on health systems worldwide. However, the lack of efficient antiviral treatment or vaccines against these highly prevalent pathogens prevents an effective management of RV-related diseases. Current advances in molecular diagnostic techniques have revealed the presence of RV in the lower respiratory tract and its role in lower airway diseases is increasingly reported. In addition to an established etiological role in the common cold, these viruses demonstrate an unexpected capacity to spread to other body sites under certain conditions. Some of these viruses have received particular attention recently, such as EV-D68 that caused a large outbreak of respiratory illness in 2014, respiratory EVs from species C, or viruses within the newly-discovered RV-C species. This review provides an update of the latest findings on clinical and fundamental aspects of RV and respiratory EV, including a summary of basic knowledge of their biology.",2016 Jan 11,"['Royston, Léna', 'Tapparel, Caroline']",Viruses,,,True
0181010a40e179c9b66d8b1f0eaac4fbf0ab6341,PMC,Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC,http://dx.doi.org/10.3390/v8010016,PMC4728576,26761027,CC BY,"Rhinoviruses (RVs) and respiratory enteroviruses (EVs) are leading causes of upper respiratory tract infections and among the most frequent infectious agents in humans worldwide. Both are classified in the Enterovirus genus within the Picornaviridae family and they have been assigned to seven distinct species, RV-A, B, C and EV-A, B, C, D. As viral infections of public health significance, they represent an important financial burden on health systems worldwide. However, the lack of efficient antiviral treatment or vaccines against these highly prevalent pathogens prevents an effective management of RV-related diseases. Current advances in molecular diagnostic techniques have revealed the presence of RV in the lower respiratory tract and its role in lower airway diseases is increasingly reported. In addition to an established etiological role in the common cold, these viruses demonstrate an unexpected capacity to spread to other body sites under certain conditions. Some of these viruses have received particular attention recently, such as EV-D68 that caused a large outbreak of respiratory illness in 2014, respiratory EVs from species C, or viruses within the newly-discovered RV-C species. This review provides an update of the latest findings on clinical and fundamental aspects of RV and respiratory EV, including a summary of basic knowledge of their biology.",2016 Jan 11,"['Royston, Léna', 'Tapparel, Caroline']",Viruses,,,True
52662ce54ce7eec49dce4d7c0592075227729f3e,PMC,Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments,http://dx.doi.org/10.3390/v8010023,PMC4728583,26797629,CC BY,"Since its emergence in the 1990s, White Spot Disease (WSD) has had major economic and societal impact in the crustacean aquaculture sector. Over the years shrimp farming alone has experienced billion dollar losses through WSD. The disease is caused by the White Spot Syndrome Virus (WSSV), a large dsDNA virus and the only member of the Nimaviridae family. Susceptibility to WSSV in a wide range of crustacean hosts makes it a major risk factor in the translocation of live animals and in commodity products. Currently there are no effective treatments for this disease. Understanding the molecular basis of disease processes has contributed significantly to the treatment of many human and animal pathogens, and with a similar aim considerable efforts have been directed towards understanding host–pathogen molecular interactions for WSD. Work on the molecular mechanisms of pathogenesis in aquatic crustaceans has been restricted by a lack of sequenced and annotated genomes for host species. Nevertheless, some of the key host–pathogen interactions have been established: between viral envelope proteins and host cell receptors at initiation of infection, involvement of various immune system pathways in response to WSSV, and the roles of various host and virus miRNAs in mitigation or progression of disease. Despite these advances, many fundamental knowledge gaps remain; for example, the roles of the majority of WSSV proteins are still unknown. In this review we assess current knowledge of how WSSV infects and replicates in its host, and critique strategies for WSD treatment.",2016 Jan 18,"['Verbruggen, Bas', 'Bickley, Lisa K.', 'van Aerle, Ronny', 'Bateman, Kelly S.', 'Stentiford, Grant D.', 'Santos, Eduarda M.', 'Tyler, Charles R.']",Viruses,,,True
5106124c0ccbe2da3746b20d396088112c6a420f,PMC,RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations,http://dx.doi.org/10.1186/s12864-016-2403-1,PMC4729133,26819139,CC BY,"BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.",2016 Jan 27,"['Hamzić, Edin', 'Kjærup, Rikke Brødsgaard', 'Mach, Núria', 'Minozzi, Guilietta', 'Strozzi, Francesco', 'Gualdi, Valentina', 'Williams, John L.', 'Chen, Jun', 'Wattrang, Eva', 'Buitenhuis, Bart', 'Juul-Madsen, Helle Risdahl', 'Dalgaard, Tina Sørensen']",BMC Genomics,,,False
70b4b035e92da4a05093847f3f31cfea47d673cc,PMC,RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations,http://dx.doi.org/10.1186/s12864-016-2403-1,PMC4729133,26819139,CC BY,"BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.",2016 Jan 27,"['Hamzić, Edin', 'Kjærup, Rikke Brødsgaard', 'Mach, Núria', 'Minozzi, Guilietta', 'Strozzi, Francesco', 'Gualdi, Valentina', 'Williams, John L.', 'Chen, Jun', 'Wattrang, Eva', 'Buitenhuis, Bart', 'Juul-Madsen, Helle Risdahl', 'Dalgaard, Tina Sørensen']",BMC Genomics,,,False
2cad52c0f90e80ad4794ba31bd99f06f211d5c2b,PMC,RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations,http://dx.doi.org/10.1186/s12864-016-2403-1,PMC4729133,26819139,CC BY,"BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.",2016 Jan 27,"['Hamzić, Edin', 'Kjærup, Rikke Brødsgaard', 'Mach, Núria', 'Minozzi, Guilietta', 'Strozzi, Francesco', 'Gualdi, Valentina', 'Williams, John L.', 'Chen, Jun', 'Wattrang, Eva', 'Buitenhuis, Bart', 'Juul-Madsen, Helle Risdahl', 'Dalgaard, Tina Sørensen']",BMC Genomics,,,False
5e9be7630693730ad6dfe2569448b33c03c12bdb,PMC,RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations,http://dx.doi.org/10.1186/s12864-016-2403-1,PMC4729133,26819139,CC BY,"BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.",2016 Jan 27,"['Hamzić, Edin', 'Kjærup, Rikke Brødsgaard', 'Mach, Núria', 'Minozzi, Guilietta', 'Strozzi, Francesco', 'Gualdi, Valentina', 'Williams, John L.', 'Chen, Jun', 'Wattrang, Eva', 'Buitenhuis, Bart', 'Juul-Madsen, Helle Risdahl', 'Dalgaard, Tina Sørensen']",BMC Genomics,,,False
1a96c7d91d342a55bcafadc1b639e2264a4daea9,PMC,RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations,http://dx.doi.org/10.1186/s12864-016-2403-1,PMC4729133,26819139,CC BY,"BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.",2016 Jan 27,"['Hamzić, Edin', 'Kjærup, Rikke Brødsgaard', 'Mach, Núria', 'Minozzi, Guilietta', 'Strozzi, Francesco', 'Gualdi, Valentina', 'Williams, John L.', 'Chen, Jun', 'Wattrang, Eva', 'Buitenhuis, Bart', 'Juul-Madsen, Helle Risdahl', 'Dalgaard, Tina Sørensen']",BMC Genomics,,,False
636512bc06a771a13d2ea72ce74f2ec2b37009c5,PMC,RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations,http://dx.doi.org/10.1186/s12864-016-2403-1,PMC4729133,26819139,CC BY,"BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.",2016 Jan 27,"['Hamzić, Edin', 'Kjærup, Rikke Brødsgaard', 'Mach, Núria', 'Minozzi, Guilietta', 'Strozzi, Francesco', 'Gualdi, Valentina', 'Williams, John L.', 'Chen, Jun', 'Wattrang, Eva', 'Buitenhuis, Bart', 'Juul-Madsen, Helle Risdahl', 'Dalgaard, Tina Sørensen']",BMC Genomics,,,False
f5f1cd43740b5b6eca8b3cf2714fc0854a746519,PMC,RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations,http://dx.doi.org/10.1186/s12864-016-2403-1,PMC4729133,26819139,CC BY,"BACKGROUND: Avian infectious bronchitis is a highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high (L10H line) and low (L10L line) serum concentration of mannose-binding lectin (MBL) were studied. In total, 32 birds from each line were used. Sixteen birds from each line were infected with IBV and sixteen were left uninfected. Eight uninfected and infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds and differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and in the same way for infected birds. Functional analysis was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. RESULTS: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” and “Somatic recombination of immunoglobulin genes involved in immune response” at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” and “Positive regulation of leukocyte activation” at weeks 1 and 3, respectively. CONCLUSIONS: Healthy birds from the two lines showed significant differences in expression profiles for subsets of adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had influenced innate as well as adaptive immunity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2403-1) contains supplementary material, which is available to authorized users.",2016 Jan 27,"['Hamzić, Edin', 'Kjærup, Rikke Brødsgaard', 'Mach, Núria', 'Minozzi, Guilietta', 'Strozzi, Francesco', 'Gualdi, Valentina', 'Williams, John L.', 'Chen, Jun', 'Wattrang, Eva', 'Buitenhuis, Bart', 'Juul-Madsen, Helle Risdahl', 'Dalgaard, Tina Sørensen']",BMC Genomics,,,True
9800de42f4f105fbd335179bef0fd6a57036d5ed,PMC,An Open Receptor-Binding Cavity of Hemagglutinin-Esterase-Fusion Glycoprotein from Newly-Identified Influenza D Virus: Basis for Its Broad Cell Tropism,http://dx.doi.org/10.1371/journal.ppat.1005411,PMC4729479,26816272,CC BY,"Influenza viruses cause seasonal flu each year and pandemics or epidemic sporadically, posing a major threat to public health. Recently, a new influenza D virus (IDV) was isolated from pigs and cattle. Here, we reveal that the IDV utilizes 9-O-acetylated sialic acids as its receptor for virus entry. Then, we determined the crystal structures of hemagglutinin-esterase-fusion glycoprotein (HEF) of IDV both in its free form and in complex with the receptor and enzymatic substrate analogs. The IDV HEF shows an extremely similar structural fold as the human-infecting influenza C virus (ICV) HEF. However, IDV HEF has an open receptor-binding cavity to accommodate diverse extended glycan moieties. This structural difference provides an explanation for the phenomenon that the IDV has a broad cell tropism. As IDV HEF is structurally and functionally similar to ICV HEF, our findings highlight the potential threat of the virus to public health.",2016 Jan 27,"['Song, Hao', 'Qi, Jianxun', 'Khedri, Zahra', 'Diaz, Sandra', 'Yu, Hai', 'Chen, Xi', 'Varki, Ajit', 'Shi, Yi', 'Gao, George F.']",PLoS Pathog,,,True
c23d0e5107a2764e299a147d41a8c76ce91c231d,PMC,Sequence-based approach for rapid identification of cross-clade CD8+ T-cell vaccine candidates from all high-risk HPV strains,http://dx.doi.org/10.1007/s13205-015-0352-z,PMC4729761,28330110,CC BY,"Human papilloma virus (HPV) is the primary etiological agent responsible for cervical cancer in women. Although in total 16 high-risk HPV strains have been identified so far. Currently available commercial vaccines are designed by targeting mainly HPV16 and HPV18 viral strains as these are the most common strains associated with cervical cancer. Because of the high level of antigenic specificity of HPV capsid antigens, the currently available vaccines are not suitable to provide cross-protection from all other high-risk HPV strains. Due to increasing reports of cervical cancer cases from other HPV high-risk strains other than HPV16 and 18, it is crucial to design vaccine that generate reasonable CD8+ T-cell responses for possibly all the high-risk strains. With this aim, we have developed a computational workflow to identify conserved cross-clade CD8+ T-cell HPV vaccine candidates by considering E1, E2, E6 and E7 proteins from all the high-risk HPV strains. We have identified a set of 14 immunogenic conserved peptide fragments that are supposed to provide protection against infection from any of the high-risk HPV strains across globe. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13205-015-0352-z) contains supplementary material, which is available to authorized users.",2016 Jun 27,"['Singh, Krishna P.', 'Verma, Neeraj', 'Akhoon, Bashir A.', 'Bhatt, Vishal', 'Gupta, Shishir K.', 'Gupta, Shailendra K.', 'Smita, Suchi']",3 Biotech,,,True
2bc8716c8d60412f241f096246127275b734635b,PMC,Education to Action: Improving Public Perception of Bats,http://dx.doi.org/10.3390/ani6010006,PMC4730123,26784239,CC BY,"Public perception of bats has historically been largely negative with bats often portrayed as carriers of disease. Bats are commonly associated with vampire lore and thus elicit largely fearful reactions despite the fact that they are a vital and valuable part of the ecosystem. Bats provide a variety of essential services from pest control to plant pollination. Despite the benefits of bats to the environment and the economy, bats are suffering at the hands of humans. They are victims of turbines, human encroachment, pesticides, and, most recently, white nose syndrome. Because of their critical importance to the environment, humans should do what they can to help protect bats. We propose that humans will be more likely to do so if their perceptions and attitudes toward bats can be significantly improved. In a preliminary study we found some support for the idea that people can be educated about bats through bat oriented events and exhibits, and that this greater knowledge can inspire humans to act to save bats.",2016 Jan 15,"['Hoffmaster, Eric', 'Vonk, Jennifer', 'Mies, Rob']",Animals (Basel),,,True
3f21f365d6a8983fd6cf0406c66d2785d0c3a138,PMC,The Roles of RNase-L in Antimicrobial Immunity and the Cytoskeleton-Associated Innate Response,http://dx.doi.org/10.3390/ijms17010074,PMC4730318,26760998,CC BY,"The interferon (IFN)-regulated endoribonuclease RNase-L is involved in multiple aspects of the antimicrobial innate immune response. It is the terminal component of an RNA cleavage pathway in which dsRNA induces the production of RNase-L-activating 2-5A by the 2′-5′-oligoadenylate synthetase. The active nuclease then cleaves ssRNAs, both cellular and viral, leading to downregulation of their expression and the generation of small RNAs capable of activating retinoic acid-inducible gene-I (RIG-I)-like receptors or the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome. This leads to IFNβ expression and IL-1β activation respectively, in addition to broader effects on immune cell function. RNase-L is also one of a growing number of innate immune components that interact with the cell cytoskeleton. It can bind to several cytoskeletal proteins, including filamin A, an actin-binding protein that collaborates with RNase-L to maintain the cellular barrier to viral entry. This antiviral activity is independent of catalytic function, a unique mechanism for RNase-L. We also describe here the interaction of RNase-L with the E3 ubiquitin ligase and scaffolding protein, ligand of nump protein X (LNX), a regulator of tight junction proteins. In order to better understand the significance and context of these novel binding partners in the antimicrobial response, other innate immune protein interactions with the cytoskeleton are also discussed.",2016 Jan 8,"['Ezelle, Heather J.', 'Malathi, Krishnamurthy', 'Hassel, Bret A.']",Int J Mol Sci,,,True
eb856c32c1a41e6513729e126e84e639ce4f5a68,PMC,Prevalence and risk factors for viral exposure in rural dogs around protected areas of the Atlantic forest,http://dx.doi.org/10.1186/s12917-016-0646-3,PMC4730773,26822375,CC BY,"BACKGROUND: Despite the crucial role of domestic dogs as reservoirs for zoonosis and some of the most threatening diseases for wild carnivores such as distemper and parvovirosis, little is known about the epidemiological features and the risk factors involved in pathogen exposure of dogs that live in human/wildlife interfaces and actually contacts wildlife. Through a cross-sectional serological approach and questionnaire survey, we assessed the prevalence along with individual and environment-associated risk factors for four important viral diseases of rural dogs living in households around six Atlantic Forest fragments in southeast Brazil. RESULTS: Widespread exposure to canine parvovirus (97 %), canine distemper virus (15 %) and canine adenovirus (27 %) was detected, but none for canine coronavirus. Dogs from small private reserves were more exposed to parvovirus and canine distemper virus than those from larger state parks. Exposure was associated with dog sex and age, lack of health care and the number of people in the households. Remarkably, factors linked to free-ranging behaviour of dogs were associated with the exposure for all pathogens detected. CONCLUSIONS: According to identified associations, reducing viral pathogen exposure in dogs will require inhibiting dog’s movements and access to nearby forests and villages and improving veterinary assistance. Promoting dog vaccination and population control through sterilization around protected areas is also necessary. The study provides support for preventive management actions aimed to protect the health of rural dogs, and consequently of Atlantic Forest’s wild carnivores.",2016 Jan 28,"['Curi, Nelson Henrique de Almeida', 'Massara, Rodrigo Lima', 'de Oliveira Paschoal, Ana Maria', 'Soriano-Araújo, Amanda', 'Lobato, Zélia Inês Portela', 'Demétrio, Guilherme Ramos', 'Chiarello, Adriano Garcia', 'Passamani, Marcelo']",BMC Vet Res,,,True
5bb362d1be223686ad4467e317cf5abb8383ab3e,PMC,"Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar – Aetiologies, Antibiotic Treatment and Outcome",http://dx.doi.org/10.1371/journal.pone.0146054,PMC4731140,26821179,CC BY,"BACKGROUND: Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission. METHODS: We prospectively studied the aetiology of febrile illness in 677 children aged 2–59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated. FINDINGS: NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require antibiotics. Clinical outcome was generally good. However, two children died. Only 68 (11%) patients remained febrile on day 3 and three of them had verified fever on day 14. An additional 29 (4.5%) children had fever relapse on day 14. Regression analysis determined C-reactive Protein (CRP) as the only independent variable significantly associated with CXR-confirmed pneumonia. CONCLUSIONS: This is the first study on uncomplicated febrile illness in African children that both applied a comprehensive laboratory panel and a healthy control group. A majority of patients had viral respiratory tract infection. Pathogens were frequently detected by qPCR also in asymptomatic children, demonstrating the importance of incorporating controls in fever aetiology studies. The precision of IMCI for identifying infections requiring antibiotics was low.",2016 Jan 28,"['Elfving, Kristina', 'Shakely, Deler', 'Andersson, Maria', 'Baltzell, Kimberly', 'Ali, Abdullah S.', 'Bachelard, Marc', 'Falk, Kerstin I.', 'Ljung, Annika', 'Msellem, Mwinyi I.', 'Omar, Rahila S.', 'Parola, Philippe', 'Xu, Weiping', 'Petzold, Max', 'Trollfors, Birger', 'Björkman, Anders', 'Lindh, Magnus', 'Mårtensson, Andreas']",PLoS One,,,True
926c0d5330eefdb58452c054c8387da92e9d0590,PMC,Experimental feline enteric coronavirus infection reveals an aberrant infection pattern and shedding of mutants with impaired infectivity in enterocyte cultures,http://dx.doi.org/10.1038/srep20022,PMC4731813,26822958,CC BY,"Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection. Since many virological and immunological data on FECV infections are lacking, the present study investigated these missing links during experimental infection of three SPF cats with FECV strain UCD. Two cats showed mild clinical signs, faecal shedding of infectious virus from 4 dpi, a cell-associated viraemia at inconsistent time points from 5 dpi, a highly neutralising antibody response from 9 dpi, and no major abnormalities in leukocyte numbers. Faecal shedding lasted for 28–56 days, but virus shed during this stage was less infectious in enterocyte cultures and affected by mutations. Remarkably, in the other cat neither clinical signs nor acute shedding were seen, but virus was detected in blood cells from 3 dpi, and shedding of non-enterotropic, mutated viruses suddenly occurred from 14 dpi onwards. Neutralising antibodies arose from 21 dpi. Leukocyte numbers were not different compared to the other cats, except for the CD8(+) regulatory T cells. These data indicate that FECV can infect immune cells even in the absence of intestinal replication and raise the hypothesis that the gradual adaptation to these cells can allow non-enterotropic mutants to arise.",2016 Jan 29,"['Desmarets, Lowiese M. B.', 'Vermeulen, Ben L.', 'Theuns, Sebastiaan', 'Conceição-Neto, Nádia', 'Zeller, Mark', 'Roukaerts, Inge D. M.', 'Acar, Delphine D.', 'Olyslaegers, Dominique A. J.', 'Van Ranst, Marc', 'Matthijnssens, Jelle', 'Nauwynck, Hans J.']",Sci Rep,,,True
77d34e9158807dab65379240836e8a73dd02e2d2,PMC,Construction of the influenza A virus transmission tree in a college-based population: co-transmission and interactions between influenza A viruses,http://dx.doi.org/10.1186/s12879-016-1373-x,PMC4731987,26825326,CC BY,"BACKGROUND: Co-infection of different influenza A viruses is known to occur but how viruses interact within co-infection remains unknown. An outbreak in a college campus during the 2009 pandemic involved two subtypes of influenza A: persons infected with pandemic A/H1N1; persons infected with seasonal A/H3N2 viruses; and persons infected with both at the same time (co-infection). This provides data to analyse the possible interaction between influenza A viruses within co-infection. METHODS: We extend a statistical inference method designed for outbreaks caused by one virus to that caused by two viruses. The method uses knowledge of which subtype each case is infected with (and whether they were co-infected), contact information and symptom onset date of each case in the influenza outbreak. We then apply it to construct the most likely transmission tree during the outbreak in the college campus. RESULTS: Analysis of the constructed transmission tree shows that the simultaneous presence of the two influenza viruses increases the infectivity and the transmissibility of A/H1N1 virus but whether it changes the infectivity of A/H3N2 is unclear. The estimation also shows that co-transmission of both subtypes from co-infection is low and therefore co-infection cannot be sustained on its own. CONCLUSIONS: This study suggests that influenza A viruses within co-infected patients can interact in some ways rather than transmit independently, and this can enhance the spread of influenza A virus infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1373-x) contains supplementary material, which is available to authorized users.",2016 Jan 29,"['Zhang, Xu-Sheng', 'De Angelis, Daniela']",BMC Infect Dis,,,True
55a2b6184753d85b19f0425ac2d68868e73248b7,PMC,Use of Piezoelectric Immunosensors for Detection of Interferon-Gamma Interaction with Specific Antibodies in the Presence of Released-Active Forms of Antibodies to Interferon-Gamma,http://dx.doi.org/10.3390/s16010096,PMC4732129,26791304,CC BY,"In preliminary ELISA studies where released-active forms (RAF) of antibodies (Abs) to interferon-gamma (IFNg) were added to the antigen-antibody system, a statistically significant difference in absorbance signals obtained in their presence in comparison to placebo was observed. A piezoelectric immunosensor assay was developed to support these data and investigate the effects of RAF Abs to IFNg on the specific interaction between Abs to IFNg and IFNg. The experimental conditions were designed and optimal electrode coating, detection circumstances and suitable chaotropic agents for electrode regeneration were selected. The developed technique was found to provide high repeatability, intermediate precision and specificity. The difference between the analytical signals of RAF Ab samples and those of the placebo was up to 50.8%, whereas the difference between non-specific controls and the placebo was within 5%–6%. Thus, the piezoelectric immunosensor as well as ELISA has the potential to be used for detecting the effects of RAF Abs to IFNg on the antigen-antibody interaction, which might be the result of RAF’s ability to modify the affinity of IFNg to specific/related Abs.",2016 Jan 20,"['Don, Elena', 'Farafonova, Olga', 'Pokhil, Suzanna', 'Barykina, Darya', 'Nikiforova, Marina', 'Shulga, Darya', 'Borshcheva, Alena', 'Tarasov, Sergey', 'Ermolaeva, Tatyana', 'Epstein, Oleg']",Sensors (Basel),,,True
81efe68611a25f79f0f485a2116a213080a38233,PMC,Use of Piezoelectric Immunosensors for Detection of Interferon-Gamma Interaction with Specific Antibodies in the Presence of Released-Active Forms of Antibodies to Interferon-Gamma,http://dx.doi.org/10.3390/s16010096,PMC4732129,26791304,CC BY,"In preliminary ELISA studies where released-active forms (RAF) of antibodies (Abs) to interferon-gamma (IFNg) were added to the antigen-antibody system, a statistically significant difference in absorbance signals obtained in their presence in comparison to placebo was observed. A piezoelectric immunosensor assay was developed to support these data and investigate the effects of RAF Abs to IFNg on the specific interaction between Abs to IFNg and IFNg. The experimental conditions were designed and optimal electrode coating, detection circumstances and suitable chaotropic agents for electrode regeneration were selected. The developed technique was found to provide high repeatability, intermediate precision and specificity. The difference between the analytical signals of RAF Ab samples and those of the placebo was up to 50.8%, whereas the difference between non-specific controls and the placebo was within 5%–6%. Thus, the piezoelectric immunosensor as well as ELISA has the potential to be used for detecting the effects of RAF Abs to IFNg on the antigen-antibody interaction, which might be the result of RAF’s ability to modify the affinity of IFNg to specific/related Abs.",2016 Jan 20,"['Don, Elena', 'Farafonova, Olga', 'Pokhil, Suzanna', 'Barykina, Darya', 'Nikiforova, Marina', 'Shulga, Darya', 'Borshcheva, Alena', 'Tarasov, Sergey', 'Ermolaeva, Tatyana', 'Epstein, Oleg']",Sensors (Basel),,,False
585a9f7b2e41ffc6ead4df982ba9d0b0adb28f51,PMC,Self-disseminating vaccines for emerging infectious diseases,http://dx.doi.org/10.1586/14760584.2016.1106942,PMC4732410,26524478,CC BY,"Modern human activity fueled by economic development is profoundly altering our relationship with microorganisms. This altered interaction with microbes is believed to be the major driving force behind the increased rate of emerging infectious diseases from animals. The spate of recent infectious disease outbreaks, including Ebola virus disease and Middle East respiratory syndrome, emphasize the need for development of new innovative tools to manage these emerging diseases. Disseminating vaccines are one such novel approach to potentially interrupt animal to human (zoonotic) transmission of these pathogens.",2016 Jan 2,"['Murphy, Aisling A.', 'Redwood, Alec J.', 'Jarvis, Michael A.']",Expert Rev Vaccines,,,True
10a9a18d6d821b917178be32b20f98c9e21d6028,PMC,A Novel High-Throughput Method for Molecular Detection of Human Pathogenic Viruses Using a Nanofluidic Real-Time PCR System,http://dx.doi.org/10.1371/journal.pone.0147832,PMC4732599,26824897,CC BY,"Human enteric viruses are recognized as the main causes of food- and waterborne diseases worldwide. Sensitive and quantitative detection of human enteric viruses is typically achieved through quantitative RT-PCR (RT-qPCR). A nanofluidic real-time PCR system was used to develop novel high-throughput methods for qualitative molecular detection (RT-qPCR array) and quantification of human pathogenic viruses by digital RT-PCR (RT-dPCR). The performance of high-throughput PCR methods was investigated for detecting 19 human pathogenic viruses and two main process controls used in food virology. The conventional real-time PCR system was compared to the RT-dPCR and RT-qPCR array. Based on the number of genome copies calculated by spectrophotometry, sensitivity was found to be slightly better with RT-qPCR than with RT-dPCR for 14 viruses by a factor range of from 0.3 to 1.6 log(10). Conversely, sensitivity was better with RT-dPCR than with RT-qPCR for seven viruses by a factor range of from 0.10 to 1.40 log(10). Interestingly, the number of genome copies determined by RT-dPCR was always from 1 to 2 log(10) lower than the expected copy number calculated by RT-qPCR standard curve. The sensitivity of the RT-qPCR and RT-qPCR array assays was found to be similar for two viruses, and better with RT-qPCR than with RT-qPCR array for eighteen viruses by a factor range of from 0.7 to 3.0 log(10). Conversely, sensitivity was only 0.30 log(10) better with the RT-qPCR array than with conventional RT-qPCR assays for norovirus GIV detection. Finally, the RT-qPCR array and RT-dPCR assays were successfully used together to screen clinical samples and quantify pathogenic viruses. Additionally, this method made it possible to identify co-infection in clinical samples. In conclusion, given the rapidity and potential for large numbers of viral targets, this nanofluidic RT-qPCR assay should have a major impact on human pathogenic virus surveillance and outbreak investigations and is likely to be of benefit to public health.",2016 Jan 29,"['Coudray-Meunier, Coralie', 'Fraisse, Audrey', 'Martin-Latil, Sandra', 'Delannoy, Sabine', 'Fach, Patrick', 'Perelle, Sylvie']",PLoS One,,,True
8826961991932d2c6c8f72d0ad2b02a625faa4f5,PMC,"Characterization of Rv0888, a Novel Extracellular Nuclease from Mycobacterium tuberculosis",http://dx.doi.org/10.1038/srep19033,PMC4733049,26742696,CC BY,"Bacterial extracellular nucleases play important roles in virulence, biofilm formation, utilization of extracellular DNA as a nutrient, and degradation of neutrophil DNA extracellular traps. However, there is no current data available for extracellular nucleases derived from M. tuberculosis. Herein, we have identified and characterized Rv0888, an extracellular nuclease in M. tuberculosis. The protein was overexpressed in E. coli, and the purified Rv0888 protein was found to require divalent cations for activity, with an optimal temperature and pH of 41 °C and 6.5, respectively. Further results demonstrated that Rv0888 nuclease activity could be inhibited by four Chinese medicine monomers. Based on sequence analysis, Rv0888 nuclease exhibited no homology with any known extracellular nucleases, indicating that Rv0888 is a novel nuclease. Site-directed mutagenesis studies revealed that the H353, D387, and D438 residues play catalytic roles in Rv0888. In vivo infection studies confirmed that Rv0888 is required for infection and is related to pathogenicity, as the persistent ability of recombinant Mycobacterium smegmatis (rMS) Rv0888NS/MS and Rv0888S/MS is significantly higher than pMV262/MS in the lung tissue, and the Rv0888NS/MS and Rv0888S/MS could produce pathological changes in the mice lung. These results show that Rv0888 is relevant to pathogenicity of M. tuberculosis.",2016 Jan 8,"['Dang, Guanghui', 'Cao, Jun', 'Cui, Yingying', 'Song, Ningning', 'Chen, Liping', 'Pang, Hai', 'Liu, Siguo']",Sci Rep,,,True
d18e10321c54248f5fdfdac2501f5368ac8052c7,PMC,Neuropathogenicity of Two Saffold Virus Type 3 Isolates in Mouse Models,http://dx.doi.org/10.1371/journal.pone.0148184,PMC4734772,26828718,CC BY,"OBJECTIVE: Saffold virus (SAFV), a picornavirus, is occasionally detected in children with acute flaccid paralysis, meningitis, and cerebellitis; however, the neuropathogenicity of SAFV remains undetermined. METHODS: The virulence of two clinical isolates of SAFV type 3 (SAFV-3) obtained from a patient with aseptic meningitis (AM strain) and acute upper respiratory inflammation (UR strain) was analyzed in neonatal and young mice utilizing virological, pathological, and immunological methods. RESULTS: The polyproteins of the strains differed in eight amino acids. Both clinical isolates were infective, exhibited neurotropism, and were mildly neurovirulent in neonatal ddY mice. Both strains pathologically infected neural progenitor cells and glial cells, but not large neurons, with the UR strain also infecting epithelial cells. UR infection resulted in longer inflammation in the brain and spinal cord because of demyelination, while the AM strain showed more infectivity in the cerebellum in neonatal ddY mice. Additionally, young BALB/c mice seroconverted following mucosal inoculation with the UR, but not the AM, strain. CONCLUSIONS: Both SAFV-3 isolates had neurotropism and mild neurovirulence but showed different cell tropisms in both neonatal and young mouse models. This animal model has the potential to recapitulate the potential neuropathogenicity of SAFV-3.",2016 Feb 1,"['Kotani, Osamu', 'Naeem, Asif', 'Suzuki, Tadaki', 'Iwata-Yoshikawa, Naoko', 'Sato, Yuko', 'Nakajima, Noriko', 'Hosomi, Takushi', 'Tsukagoshi, Hiroyuki', 'Kozawa, Kunihisa', 'Hasegawa, Hideki', 'Taguchi, Fumihiro', 'Shimizu, Hiroyuki', 'Nagata, Noriyo']",PLoS One,,,True
c481fdcf995099e14997dabd9fe3b47ce8784020,PMC,Prevalence and characteristics of hypoxic hepatitis in the largest single-centre cohort of avian influenza A(H7N9) virus-infected patients with severe liver impairment in the intensive care unit,http://dx.doi.org/10.1038/emi.2016.1,PMC4735056,26733380,CC BY,"Avian influenza A(H7N9) virus (A(H7N9)) emerged in February 2013. Liver impairment of unknown cause is present in 29% of patients with A(H7N9) infection, some of whom experience severe liver injury. Hypoxic hepatitis (HH) is a type of acute severe liver injury characterized by an abrupt, massive increase in serum aminotransferases resulting from anoxic centrilobular necrosis of liver cells. In the intensive care unit (ICU), the prevalence of HH is ∼1%–2%. Here, we report a 1.8% (2/112) incidence of HH in the largest single-centre cohort of ICU patients with A(H7N9) infection. Both HH patients presented with multiple organ failure (MOF) involving respiratory, cardiac, circulatory and renal failure and had a history of chronic heart disease. On admission, severe liver impairment was found. Peak alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values were 937 and 1281 U/L, and 3117 and 3029 U/L, respectively, in the two patients. Unfortunately, both patients died due to deterioration of MOF. A post-mortem biopsy in case 1 confirmed the presence of centrilobular necrosis of the liver, and real-time reverse transcription polymerase chain reaction of A(H7N9)-specific genes was negative, which excluded A(H7N9)-related hepatitis. The incidence of HH in A(H7N9) patients is similar to that in ICU patients with other aetiologies. It seems that patients with A(H7N9) infection and a history of chronic heart disease with a low left ventricular ejection fraction on admission are susceptible to HH, which presents as a marked elevation in ALT at the time of admission.",2016 Jan 6,"['Zhang, YiMin', 'Liu, JiMin', 'Yu, Liang', 'Zhou, Ning', 'Ding, Wei', 'Zheng, ShuFa', 'Shi, Ding', 'Li, LanJuan']",Emerg Microbes Infect,,,True
525c07cc621b7185fb0d224710d883f523d08ba3,PMC,"Molecular characterization of human coronaviruses and their circulation dynamics in Kenya, 2009–2012",http://dx.doi.org/10.1186/s12985-016-0474-x,PMC4736488,26833249,CC BY,"BACKGROUND: Human Coronaviruses (HCoV) are a common cause of respiratory illnesses and are responsible for considerable morbidity and hospitalization across all age groups especially in individuals with compromised immunity. There are six known species of HCoV: HCoV-229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43, MERS-CoV and SARS-HCoV. Although studies have shown evidence of global distribution of HCoVs, there is limited information on their presence and distribution in Kenya. METHODS: HCoV strains that circulated in Kenya were retrospectively diagnosed and molecularly characterized. A total of 417 nasopharyngeal specimens obtained between January 2009 and December 2012 from around Kenya were analyzed by a real time RT-PCR using HCoV-specific primers. HCoV-positive specimens were subsequently inoculated onto monolayers of LL-CMK2 cells. The isolated viruses were characterized by RT-PCR amplification and sequencing of the partial polymerase (pol) gene. RESULTS: The prevalence of HCoV infection was as follows: out of the 417 specimens, 35 (8.4 %) were positive for HCoV, comprising 10 (2.4 %) HCoV-NL63, 12 (2.9 %) HCoV-OC43, 9 (2.1 %) HCoV-HKU1, and 4 (1 %) HCoV-229E. The Kenyan HCoV strains displayed high sequence homology to the prototypes and contemporaneous strains. Evolution analysis showed that the Kenyan HCoV-OC43 and HCoV-NL63 isolates were under purifying selection. Phylogenetic evolutionary analyses confirmed the identities of three HCoV-HKU1, five HCoV-NL63, eight HCoV-OC43 and three HCoV-229E. CONCLUSIONS: There were yearly variations in the prevalence and circulation patterns of individual HCoVs in Kenya. This paper reports on the first molecular characterization of human Coronaviruses in Kenya, which play an important role in causing acute respiratory infections among children.",2016 Feb 1,"['Sipulwa, Lenata A.', 'Ongus, Juliette R.', 'Coldren, Rodney L.', 'Bulimo, Wallace D.']",Virol J,,,True
e745a55d651d2f45443c39ed949185d8f968500a,PMC,Multiple Cis-acting elements modulate programmed -1 ribosomal frameshifting in Pea enation mosaic virus,http://dx.doi.org/10.1093/nar/gkv1241,PMC4737148,26578603,CC BY,"Programmed -1 ribosomal frameshifting (-1 PRF) is used by many positive-strand RNA viruses for translation of required products. Despite extensive studies, it remains unresolved how cis-elements just downstream of the recoding site promote a precise level of frameshifting. The Umbravirus Pea enation mosaic virus RNA2 expresses its RNA polymerase by -1 PRF of the 5′-proximal ORF (p33). Three hairpins located in the vicinity of the recoding site are phylogenetically conserved among Umbraviruses. The central Recoding Stimulatory Element (RSE), located downstream of the p33 termination codon, is a large hairpin with two asymmetric internal loops. Mutational analyses revealed that sequences throughout the RSE and the RSE lower stem (LS) structure are important for frameshifting. SHAPE probing of mutants indicated the presence of higher order structure, and sequences in the LS may also adapt an alternative conformation. Long-distance pairing between the RSE and a 3′ terminal hairpin was less critical when the LS structure was stabilized. A basal level of frameshifting occurring in the absence of the RSE increases to 72% of wild-type when a hairpin upstream of the slippery site is also deleted. These results suggest that suppression of frameshifting may be needed in the absence of an active RSE conformation.",2016 Jan 29,"['Gao, Feng', 'Simon, Anne E.']",Nucleic Acids Res,,,True
8c2e819ffac93b6796d3d9fdf7ccc8e67c397a31,PMC,Domain swapping oligomerization of thermostable c-type cytochrome in E. coli cells,http://dx.doi.org/10.1038/srep19334,PMC4738263,26838805,CC BY,"Knowledge on domain swapping in vitro is increasing, but domain swapping may not occur regularly in vivo, and its information in cells is limited. Herein, we show that domain-swapped oligomers of a thermostable c-type cytochrome, Hydrogenobacter thermophilus cyt c(552), are formed in E. coli which expresses cyt c(552). The region containing the N-terminal α-helix and heme was domain-swapped between protomers in the dimer formed in E. coli. The amount of cyt c(552) oligomers increased in E. coli as the cyt c(552) concentration was increased, whereas that of high-order oligomers decreased in the order of decrease in protein stability, indicating that domain swapping decreases in cells when the protein stability decreases. Apo cyt c(552) was detected in the cyt c(552) oligomer formed in E. coli, but not in that of the A5F/M11V/Y32F/Y41E/I76V mutant. The cyt c(552) oligomer containing its apo protein may form at the periplasm, since the apo protein detected by mass measurements did not contain the signal peptide. These results show that domain-swapped cyt c(552) oligomers were formed in E. coli, owing to the stability of the transient oligomer containing the apo protein before heme attachment. This is an indication that exceedingly stable proteins may have disadvantages forming domain-swapped oligomers in cells.",2016 Feb 3,"['Hayashi, Yugo', 'Yamanaka, Masaru', 'Nagao, Satoshi', 'Komori, Hirofumi', 'Higuchi, Yoshiki', 'Hirota, Shun']",Sci Rep,,,True
4c5661848b054307106bd3b67311da7effd797a8,PMC,Domain swapping oligomerization of thermostable c-type cytochrome in E. coli cells,http://dx.doi.org/10.1038/srep19334,PMC4738263,26838805,CC BY,"Knowledge on domain swapping in vitro is increasing, but domain swapping may not occur regularly in vivo, and its information in cells is limited. Herein, we show that domain-swapped oligomers of a thermostable c-type cytochrome, Hydrogenobacter thermophilus cyt c(552), are formed in E. coli which expresses cyt c(552). The region containing the N-terminal α-helix and heme was domain-swapped between protomers in the dimer formed in E. coli. The amount of cyt c(552) oligomers increased in E. coli as the cyt c(552) concentration was increased, whereas that of high-order oligomers decreased in the order of decrease in protein stability, indicating that domain swapping decreases in cells when the protein stability decreases. Apo cyt c(552) was detected in the cyt c(552) oligomer formed in E. coli, but not in that of the A5F/M11V/Y32F/Y41E/I76V mutant. The cyt c(552) oligomer containing its apo protein may form at the periplasm, since the apo protein detected by mass measurements did not contain the signal peptide. These results show that domain-swapped cyt c(552) oligomers were formed in E. coli, owing to the stability of the transient oligomer containing the apo protein before heme attachment. This is an indication that exceedingly stable proteins may have disadvantages forming domain-swapped oligomers in cells.",2016 Feb 3,"['Hayashi, Yugo', 'Yamanaka, Masaru', 'Nagao, Satoshi', 'Komori, Hirofumi', 'Higuchi, Yoshiki', 'Hirota, Shun']",Sci Rep,,,True
278697db1668e58b24cd105be09208d7f1bc1119,PMC,Respiratory Viruses Associated Hospitalization among Children Aged <5 Years in Bangladesh: 2010-2014,http://dx.doi.org/10.1371/journal.pone.0147982,PMC4739641,26840782,CC0,"BACKGROUND: We combined hospital-based surveillance and health utilization survey data to estimate the incidence of respiratory viral infections associated hospitalization among children aged < 5 years in Bangladesh. METHODS: Surveillance physicians collected respiratory specimens from children aged <5 years hospitalized with respiratory illness and residing in the primary hospital catchment areas. We tested respiratory specimens for respiratory syncytial virus, parainfluenza viruses, human metapneumovirus, influenza, adenovirus and rhinoviruses using rRT-PCR. During 2013, we conducted a health utilization survey in the primary catchment areas of the hospitals to determine the proportion of all hospitalizations for respiratory illness among children aged <5 years at the surveillance hospitals during the preceding 12 months. We estimated the respiratory virus-specific incidence of hospitalization by dividing the estimated number of hospitalized children with a laboratory confirmed infection with a respiratory virus by the population aged <5 years of the catchment areas and adjusted for the proportion of children who were hospitalized at the surveillance hospitals. RESULTS: We estimated that the annual incidence per 1000 children (95% CI) of all cause associated respiratory hospitalization was 11.5 (10–12). The incidences per 1000 children (95% CI) per year for respiratory syncytial virus, parainfluenza, adenovirus, human metapneumovirus and influenza infections were 3(2–3), 0.5(0.4–0.8), 0.4 (0.3–0.6), 0.4 (0.3–0.6), and 0.4 (0.3–0.6) respectively. The incidences per 1000 children (95%CI) of rhinovirus-associated infections among hospitalized children were 5 (3–7), 2 (1–3), 1 (0.6–2), and 3 (2–4) in 2010, 2011, 2012 and 2013, respectively. CONCLUSION: Our data suggest that respiratory viruses are associated with a substantial burden of hospitalization in children aged <5 years in Bangladesh.",2016 Feb 3,"['Homaira, Nusrat', 'Luby, Stephen P.', 'Hossain, Kamal', 'Islam, Kariul', 'Ahmed, Makhdum', 'Rahman, Mustafizur', 'Rahman, Ziaur', 'Paul, Repon C.', 'Bhuiyan, Mejbah Uddin', 'Brooks, W. Abdullah', 'Sohel, Badrul Munir', 'Banik, Kajal Chandra', 'Widdowson, Marc-Alain', 'Willby, Melisa', 'Rahman, Mahmudur', 'Bresee, Joseph', 'Ramirez, Katharine-Sturm', 'Azziz-Baumgartner, Eduardo']",PLoS One,,,True
b2511d6e6a5faa918701cd2bf6e2641ba7f4c9cd,PMC,Epstein- Barr Virus: Clinical and Epidemiological Revisits and Genetic Basis of Oncogenesis,http://dx.doi.org/10.2174/1874357901509010007,PMC4740969,26862355,CC BY,"Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancies",2015 Nov 3,"['Ali, Abdelwahid Saeed', 'Al-Shraim, Mubarak', 'Al-Hakami, Ahmed Musa', 'Jones, Ian M']",Open Virol J,,,True
4ef6fc1277c3190055c77131bd2030f18ecb54ac,PMC,Antigen Production in Plant to Tackle Infectious Diseases Flare Up: The Case of SARS,http://dx.doi.org/10.3389/fpls.2016.00054,PMC4742786,26904039,CC BY,"Severe acute respiratory syndrome (SARS) is a dangerous infection with pandemic potential. It emerged in 2002 and its aetiological agent, the SARS Coronavirus (SARS-CoV), crossed the species barrier to infect humans, showing high morbidity and mortality rates. No vaccines are currently licensed for SARS-CoV and important efforts have been performed during the first outbreak to develop diagnostic tools. Here we demonstrate the transient expression in Nicotiana benthamiana of two important antigenic determinants of the SARS-CoV, the nucleocapsid protein (N) and the membrane protein (M) using a virus-derived vector or agro-infiltration, respectively. For the M protein, this is the first description of production in plants, while for plant-derived N protein we demonstrate that it is recognized by sera of patients from the SARS outbreak in Hong Kong in 2003. The availability of recombinant N and M proteins from plants opens the way to further evaluation of their potential utility for the development of diagnostic and protection/therapy tools to be quickly manufactured, at low cost and with minimal risk, to face potential new highly infectious SARS-CoV outbreaks.",2016 Feb 5,"['Demurtas, Olivia C.', 'Massa, Silvia', 'Illiano, Elena', 'De Martinis, Domenico', 'Chan, Paul K. S.', 'Di Bonito, Paola', 'Franconi, Rosella']",Front Plant Sci,,,True
cc66ac23fd5a72e5bf95bad4be77eb93527562d9,PMC,"Estimation of the Basic Reproductive Number and Mean Serial Interval of a Novel Pathogen in a Small, Well-Observed Discrete Population",http://dx.doi.org/10.1371/journal.pone.0148061,PMC4744020,26849644,CC BY,"BACKGROUND: Accurately assessing the transmissibility and serial interval of a novel human pathogen is public health priority so that the timing and required strength of interventions may be determined. Recent theoretical work has focused on making best use of data from the initial exponential phase of growth of incidence in large populations. METHODS: We measured generational transmissibility by the basic reproductive number R(0) and the serial interval by its mean T(g). First, we constructed a simulation algorithm for case data arising from a small population of known size with R(0) and T(g) also known. We then developed an inferential model for the likelihood of these case data as a function of R(0) and T(g). The model was designed to capture a) any signal of the serial interval distribution in the initial stochastic phase b) the growth rate of the exponential phase and c) the unique combination of R(0) and T(g) that generates a specific shape of peak incidence when the susceptible portion of a small population is depleted. FINDINGS: Extensive repeat simulation and parameter estimation revealed no bias in univariate estimates of either R(0) and T(g). We were also able to simultaneously estimate both R(0) and T(g). However, accurate final estimates could be obtained only much later in the outbreak. In particular, estimates of T(g) were considerably less accurate in the bivariate case until the peak of incidence had passed. CONCLUSIONS: The basic reproductive number and mean serial interval can be estimated simultaneously in real time during an outbreak of an emerging pathogen. Repeated application of these methods to small scale outbreaks at the start of an epidemic would permit accurate estimates of key parameters.",2016 Feb 5,"['Wu, Kendra M.', 'Riley, Steven']",PLoS One,,,True
39a1d7e4cf03a63037800c831965232d1d259e0f,PMC,Selective Degradation of Host RNA Polymerase II Transcripts by Influenza A Virus PA-X Host Shutoff Protein,http://dx.doi.org/10.1371/journal.ppat.1005427,PMC4744033,26849127,CC BY,"Influenza A viruses (IAVs) inhibit host gene expression by a process known as host shutoff. Host shutoff limits host innate immune responses and may also redirect the translation apparatus to the production of viral proteins. Multiple IAV proteins regulate host shutoff, including PA-X, a ribonuclease that remains incompletely characterized. We report that PA-X selectively targets host RNA polymerase II (Pol II) transcribed mRNAs, while sparing products of Pol I and Pol III. Interestingly, we show that PA-X can also target Pol II-transcribed RNAs in the nucleus, including non-coding RNAs that are not destined to be translated, and reporter transcripts with RNA hairpin structures that block ribosome loading. Transcript degradation likely occurs in the nucleus, as PA-X is enriched in the nucleus and its nuclear localization correlates with reduction in target RNA levels. Complete degradation of host mRNAs following PA-X-mediated endonucleolytic cleavage is dependent on the host 5’->3’-exonuclease Xrn1. IAV mRNAs are structurally similar to host mRNAs, but are synthesized and modified at the 3’ end by the action of the viral RNA-dependent RNA polymerase complex. Infection of cells with wild-type IAV or a recombinant PA-X-deficient virus revealed that IAV mRNAs resist PA-X-mediated degradation during infection. At the same time, loss of PA-X resulted in changes in the synthesis of select viral mRNAs and a decrease in viral protein accumulation. Collectively, these results significantly advance our understanding of IAV host shutoff, and suggest that the PA-X causes selective degradation of host mRNAs by discriminating some aspect of Pol II-dependent RNA biogenesis in the nucleus.",2016 Feb 5,"['Khaperskyy, Denys A.', 'Schmaling, Summer', 'Larkins-Ford, Jonah', 'McCormick, Craig', 'Gaglia, Marta M.']",PLoS Pathog,,,True
a59bbb5dd57d1aa789c638a65a93bb8ed66a5e5e,PMC,Selective Degradation of Host RNA Polymerase II Transcripts by Influenza A Virus PA-X Host Shutoff Protein,http://dx.doi.org/10.1371/journal.ppat.1005427,PMC4744033,26849127,CC BY,"Influenza A viruses (IAVs) inhibit host gene expression by a process known as host shutoff. Host shutoff limits host innate immune responses and may also redirect the translation apparatus to the production of viral proteins. Multiple IAV proteins regulate host shutoff, including PA-X, a ribonuclease that remains incompletely characterized. We report that PA-X selectively targets host RNA polymerase II (Pol II) transcribed mRNAs, while sparing products of Pol I and Pol III. Interestingly, we show that PA-X can also target Pol II-transcribed RNAs in the nucleus, including non-coding RNAs that are not destined to be translated, and reporter transcripts with RNA hairpin structures that block ribosome loading. Transcript degradation likely occurs in the nucleus, as PA-X is enriched in the nucleus and its nuclear localization correlates with reduction in target RNA levels. Complete degradation of host mRNAs following PA-X-mediated endonucleolytic cleavage is dependent on the host 5’->3’-exonuclease Xrn1. IAV mRNAs are structurally similar to host mRNAs, but are synthesized and modified at the 3’ end by the action of the viral RNA-dependent RNA polymerase complex. Infection of cells with wild-type IAV or a recombinant PA-X-deficient virus revealed that IAV mRNAs resist PA-X-mediated degradation during infection. At the same time, loss of PA-X resulted in changes in the synthesis of select viral mRNAs and a decrease in viral protein accumulation. Collectively, these results significantly advance our understanding of IAV host shutoff, and suggest that the PA-X causes selective degradation of host mRNAs by discriminating some aspect of Pol II-dependent RNA biogenesis in the nucleus.",2016 Feb 5,"['Khaperskyy, Denys A.', 'Schmaling, Summer', 'Larkins-Ford, Jonah', 'McCormick, Craig', 'Gaglia, Marta M.']",PLoS Pathog,,,False
e0e1f657eb7a089f3a2fbb4beb3dc6a242a22b34,PMC,Natural Pig Plasma Immunoglobulins Have Anti-Bacterial Effects: Potential for Use as Feed Supplement for Treatment of Intestinal Infections in Pigs,http://dx.doi.org/10.1371/journal.pone.0147373,PMC4744083,26824607,CC BY,"There is an increasing demand for non-antibiotics solutions to control infectious disease in intensive pig production. Here, one such alternative, namely pig antibodies purified from slaughterhouse blood was investigated in order to elucidate its potential usability to control post-weaning diarrhoea (PWD), which is one of the top indications for antibiotics usage in the pig production. A very cost-efficient and rapid one-step expanded bed adsorption (EBA) chromatography procedure was used to purify pig immunoglobulin G from slaughterhouse pig plasma (more than 100 litres), resulting in >85% pure pig IgG (ppIgG). The ppIgG thus comprised natural pig immunoglobulins and was subsequently shown to contain activity towards four pig-relevant bacterial strains (three different types of Escherichia coli and one type of Salmonella enterica) but not towards a fish pathogen (Yersinia ruckeri), and was demonstrated to inhibit the binding of the four pig relevant bacteria to a pig intestinal cell line (IPEC-J2). Finally it was demonstrated in an in vivo weaning piglet model for intestinal colonization with an E. coli F4+ challenge strain that ppIgG given in the feed significantly reduced shedding of the challenge strain, reduced the proportion of the bacterial family Enterobacteriaceae, increased the proportion of families Enterococcoceae and Streptococcaceae and generally increased ileal microbiota diversity. Conclusively, our data support the idea that natural IgG directly purified from pig plasma and given as a feed supplement can be used in modern swine production as an efficient and cost-effective means for reducing both occurrence of PWD and antibiotics usage and with a potential for the prevention and treatment of other intestinal infectious diseases even if the causative agent might not be known.",2016 Jan 29,"['Hedegaard, Chris J.', 'Strube, Mikael L.', 'Hansen, Marie B.', 'Lindved, Bodil K.', 'Lihme, Allan', 'Boye, Mette', 'Heegaard, Peter M. H.']",PLoS One,,,True
a1dde82e18ad108c7eedb452d50a661e647b7cf2,PMC,Coronaviruses and the human airway: a universal system for virus-host interaction studies,http://dx.doi.org/10.1186/s12985-016-0479-5,PMC4744394,26852031,CC BY,"Human coronaviruses (HCoVs) are large RNA viruses that infect the human respiratory tract. The emergence of both Severe Acute Respiratory Syndrome and Middle East Respiratory syndrome CoVs as well as the yearly circulation of four common CoVs highlights the importance of elucidating the different mechanisms employed by these viruses to evade the host immune response, determine their tropism and identify antiviral compounds. Various animal models have been established to investigate HCoV infection, including mice and non-human primates. To establish a link between the research conducted in animal models and humans, an organotypic human airway culture system, that recapitulates the human airway epithelium, has been developed. Currently, different cell culture systems are available to recapitulate the human airways, including the Air-Liquid Interface (ALI) human airway epithelium (HAE) model. Tracheobronchial HAE cultures recapitulate the primary entry point of human respiratory viruses while the alveolar model allows for elucidation of mechanisms involved in viral infection and pathogenesis in the alveoli. These organotypic human airway cultures represent a universal platform to study respiratory virus-host interaction by offering more detailed insights compared to cell lines. Additionally, the epidemic potential of this virus family highlights the need for both vaccines and antivirals. No commercial vaccine is available but various effective antivirals have been identified, some with potential for human treatment. These morphological airway cultures are also well suited for the identification of antivirals, evaluation of compound toxicity and viral inhibition.",2016 Feb 6,"['Jonsdottir, Hulda R.', 'Dijkman, Ronald']",Virol J,,,True
ea97faa57e408d3c7a5b84dbe3da7ae4feb9992e,PMC,"Rapid PCR Detection of Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum",http://dx.doi.org/10.1155/2013/168742,PMC4745450,26904723,CC BY,"Objective. We compared laboratory developed real-time PCR assays for detection of Mycoplasma hominis and for detection and differentiation of Ureaplasma urealyticum and parvum to culture using genitourinary specimens submitted for M. hominis and Ureaplasma culture. Methods. 283 genitourinary specimens received in the clinical bacteriology laboratory for M. hominis and Ureaplasma species culture were evaluated. Nucleic acids were extracted using the Total Nucleic Acid Kit on the MagNA Pure 2.0. 5 μL of the extracts were combined with 15 μL of each of the two master mixes. Assays were performed on the LightCycler 480 II system. Culture was performed using routine methods. Results. M. hominis PCR detected 38/42 M. hominis culture-positive specimens, as well as 2 that were culture negative (sensitivity, 90.5%; specificity, 99.2%). Ureaplasma PCR detected 139/144 Ureaplasma culture-positive specimens, as well as 9 that were culture negative (sensitivity, 96.5%; specificity, 93.6%). Of the specimens that tested positive for Ureaplasma species, U. urealyticum alone was detected in 33, U. parvum alone in 109, and both in 6. Conclusion. The described PCR assays are rapid alternatives to culture for detection of M. hominis and Ureaplasma species, and, unlike culture, the Ureaplasma assay easily distinguishes U. urealyticum from parvum.",2013 Mar 11,"['Cunningham, Scott A.', 'Mandrekar, Jayawant N.', 'Rosenblatt, Jon E.', 'Patel, Robin']",Int J Bacteriol,,,True
d3630872afc160701dea448dea6409e50b98642f,PMC,Quelling an innate response to dsRNA,,PMC4745674,26356565,CC BY,,2015 Aug 6,"['Ogden, Kristen M.', 'Prasad, B. V. Venkataram']",Oncotarget,,,False
b0e52525fd4deb91e0fc1fd94e9453fddce62905,PMC,Phylogenetic and Pathotypic Characterization of Newcastle Disease Viruses Circulating in South China and Transmission in Different Birds,http://dx.doi.org/10.3389/fmicb.2016.00119,PMC4746259,26903997,CC BY,"Although Newcastle disease virus (NDV) with high pathogenicity has frequently been isolated in poultry in China since 1948, the mode of its transmission among avian species remains largely unknown. Given that various wild bird species have been implicated as sources of transmission, in this study we genotypically and pathotypically characterized 23 NDV isolates collected from chickens, ducks, and pigeons in live bird markets (LBMs) in South China as part of an H7N9 surveillance program during December 2013–February 2014. To simulate the natural transmission of different kinds of animals in LBMs, we selected three representative NDVs—namely, GM, YF18, and GZ289—isolated from different birds to evaluate the pathogenicity and transmission of the indicated viruses in chickens, ducks, and pigeons. Furthermore, to investigate the replication and shedding of NDV in poultry, we inoculated the chickens, ducks, and pigeons with 10(6) EID(50) of each virus via intraocular and intranasal routes. Eight hour after infection, the naïve contact groups were housed with those inoculated with each of the viruses as a means to monitor contact transmission. Our results indicated that genetically diverse viruses circulate in LBMs in South China's Guangdong Province and that NDV from different birds have different tissue tropisms and host ranges when transmitted in different birds. We therefore propose the continuous epidemiological surveillance of LBMs to support the prevention of the spread of these viruses in different birds, especially chickens, and highlight the need for studies of the virus–host relationship.",2016 Feb 9,"['Kang, Yinfeng', 'Xiang, Bin', 'Yuan, Runyu', 'Zhao, Xiaqiong', 'Feng, Minsha', 'Gao, Pei', 'Li, Yanling', 'Li, Yulian', 'Ning, Zhangyong', 'Ren, Tao']",Front Microbiol,,,True
62a1f28a0ad0c2c37252351ad64fd7d8b0efdcc4,PMC,Comparative Analysis of Salivary Gland Proteomes of Two Glossina Species that Exhibit Differential Hytrosavirus Pathologies,http://dx.doi.org/10.3389/fmicb.2016.00089,PMC4746320,26903969,CC BY,"Glossina pallidipes salivary gland hypertrophy virus (GpSGHV; family Hytrosaviridae) is a dsDNA virus exclusively pathogenic to tsetse flies (Diptera; Glossinidae). The 190 kb GpSGHV genome contains 160 open reading frames and encodes more than 60 confirmed proteins. The asymptomatic GpSGHV infection in flies can convert to symptomatic infection that is characterized by overt salivary gland hypertrophy (SGH). Flies with SGH show reduced general fitness and reproductive dysfunction. Although the occurrence of SGH is an exception rather than the rule, G. pallidipes is thought to be the most susceptible to expression of overt SGH symptoms compared to other Glossina species that are largely asymptomatic. Although Glossina salivary glands (SGs) play an essential role in GpSGHV transmission, the functions of the salivary components during the virus infection are poorly understood. In this study, we used mass spectrometry to study SG proteomes of G. pallidipes and G. m. morsitans, two Glossina model species that exhibit differential GpSGHV pathologies (high and low incidence of SGH, respectively). A total of 540 host proteins were identified, of which 23 and 9 proteins were significantly up- and down-regulated, respectively, in G. pallidipes compared to G. m. morsitans. Whereas 58 GpSGHV proteins were detected in G. pallidipes F(1) progenies, only 5 viral proteins were detected in G. m. morsitans. Unlike in G. pallidipes, qPCR assay did not show any significant increase in virus titers in G. m. morsitans F(1) progenies, confirming that G. m. morsitans is less susceptible to GpSGHV infection and replication compared to G. pallidipes. Based on our results, we speculate that in the case of G. pallidipes, GpSGHV employs a repertoire of host intracellular signaling pathways for successful infection. In the case of G. m. morsitans, antiviral responses appeared to be dominant. These results are useful for designing additional tools to investigate the Glossina-GpSGHV interactions.",2016 Feb 9,"['Kariithi, Henry M.', 'İnce, İkbal Agah', 'Boeren, Sjef', 'Murungi, Edwin K.', 'Meki, Irene K.', 'Otieno, Everlyne A.', 'Nyanjom, Steven R. G.', 'van Oers, Monique M.', 'Vlak, Just M.', 'Abd-Alla, Adly M. M.']",Front Microbiol,,,True
481c14a837af6dd6d5a5d8f3a26ae6cc51cca2f6,PMC,Evaluation of twenty‐two rapid antigen detection tests in the diagnosis of Equine Influenza caused by viruses of H3N8 subtype,http://dx.doi.org/10.1111/irv.12358,PMC4746556,26568369,CC BY,"BACKGROUND: Equine influenza (EI) is a highly contagious disease caused by viruses of the H3N8 subtype. The rapid diagnosis of EI is essential to reduce the disease spread. Many rapid antigen detection (RAD) tests for diagnosing human influenza are available, but their ability to diagnose EI has not been systematically evaluated. OBJECTIVES: The aim of this study was to compare the performance of 22 RAD tests in the diagnosis of EI. METHODS: The 22 RAD tests were performed on fivefold serial dilutions of EI virus to determine their detection limits. The four most sensitive RAD tests (ImmunoAce Flu, BD Flu examan, Quick chaser Flu A, B and ESPLINE Influenza A&B‐N) were further evaluated using nasopharyngeal samples collected from experimentally infected and naturally infected horses. The results were compared to those obtained using molecular tests. RESULTS: The detection limits of the 22 RAD tests varied hugely. Even the four RAD tests showing the best sensitivity were 125‐fold less sensitive than the molecular techniques. The duration of virus detection in the experimentally infected horses was shorter using the RAD tests than using the molecular techniques. The RAD tests detected between 27% and 73% of real‐time RT‐PCR‐positive samples from naturally infected horses. CONCLUSIONS: The study demonstrated the importance of choosing the right RAD tests as only three of 22 were fit for diagnosing EI. It was also indicated that even RAD tests with the highest sensitivity serve only as an adjunct to molecular tests because of the potential for false‐negative results.",2016 Mar 1,"['Yamanaka, Takashi', 'Nemoto, Manabu', 'Bannai, Hiroshi', 'Tsujimura, Koji', 'Kondo, Takashi', 'Matsumura, Tomio', 'Gildea, Sarah', 'Cullinane, Ann']",Influenza Other Respir Viruses,,,True
71ff6abe3023a4c48fd6e6c54265bce395b88397,PMC,Rhinovirus‐associated pulmonary exacerbations show a lack of FEV (1) improvement in children with cystic fibrosis,http://dx.doi.org/10.1111/irv.12353,PMC4746558,26493783,CC BY,"BACKGROUND: Respiratory viral infections lead to bronchial inflammation in patients with cystic fibrosis, especially during pulmonary exacerbations. The aim of this study was to determine the impact of viral‐associated pulmonary exacerbations in children with cystic fibrosis and failure to improve forced expiratory volume in 1 s (FEV (1)) after an appropriate treatment. METHODS: We lead a pilot study from January 2009 until March 2013. Children with a diagnosis of cystic fibrosis were longitudinally evaluated three times: at baseline (Visit 1), at the diagnosis of pulmonary exacerbation (Visit 2), and after exacerbation treatment (Visit 3). Nasal and bronchial samples were analyzed at each visit with multiplex viral respiratory PCR panel (qualitative detection of 16 viruses). Pulmonary function tests were recorded at each visit, in order to highlight a possible failure to improve them after treatment. Lack of improvement was defined by an increase in FEV (1) less than 5% between Visit 2 and Visit 3. RESULTS: Eighteen children were analyzed in the study. 10 patients failed to improve by more than 5% their FEV (1) between Visit 2 and Visit 3. Rhinovirus infection at Visit 2 or Visit 3 was the only risk factor significantly associated with such a failure (OR, 12; 95% CI, 1·3–111·3), P = 0·03. CONCLUSIONS: Rhinovirus infection seems to play a role in the FEV (1) recovery after pulmonary exacerbation treatment in children with cystic fibrosis. Such an association needs to be confirmed by a large‐scale study because this finding may have important implications for pulmonary exacerbation management.",2016 Mar 29,"['Cousin, Mathias', 'Molinari, Nicolas', 'Foulongne, Vincent', 'Caimmi, Davide', 'Vachier, Isabelle', 'Abely, Michel', 'Chiron, Raphael']",Influenza Other Respir Viruses,,,True
b0bb72323af0b1a945243ed46769e00f6d9ceca2,PMC,"Survey of influenza and other respiratory viruses diagnostic testing in US hospitals, 2012–2013",http://dx.doi.org/10.1111/irv.12355,PMC4746564,26505742,CC BY,"BACKGROUND: Little is known about laboratory capacity to routinely diagnose influenza and other respiratory viruses at clinical laboratories and hospitals. AIMS: We sought to assess diagnostic practices for influenza and other respiratory virus in a survey of hospitals and laboratories participating in the US Influenza Hospitalization Surveillance Network in 2012–2013. MATERIALS AND METHODS: All hospitals and their associated laboratories participating in the Influenza Hospitalization Surveillance Network (FluSurv‐NET) were included in this evaluation. The network covers more than 80 counties in 15 states, CA, CO, CT, GA, MD, MN, NM, NY, OR, TN, IA, MI, OH, RI, and UT, with a catchment population of ~28 million people. We administered a standardized questionnaire to key personnel, including infection control practitioners and laboratory departments, at each hospital through telephone interviews. RESULTS: Of the 240 participating laboratories, 67% relied only on commercially available rapid influenza diagnostic tests to diagnose influenza. Few reported the availability of molecular diagnostic assays for detection of influenza (26%) and other viral pathogens (≤20%) in hospitals and commercial laboratories. CONCLUSION: Reliance on insensitive assays to detect influenza may detract from optimal clinical management of influenza infections in hospitals.",2016 Mar 29,"['Su, Su', 'Fry, Alicia M.', 'Kirley, Pam Daily', 'Aragon, Deborah', 'Yousey‐Hindes, Kimberly', 'Meek, James', 'Openo, Kyle', 'Oni, Oluwakemi', 'Sharangpani, Ruta', 'Morin, Craig', 'Hollick, Gary', 'Lung, Krista', 'Laidler, Matt', 'Lindegren, Mary Lou', 'Schaffner, William', 'Atkinson, Annette', 'Chaves, Sandra S.']",Influenza Other Respir Viruses,,,True
80eae3b5b1d0ba7f1806d637628b15ae10e342c4,PMC,"Influenza hospitalization epidemiology from a severe acute respiratory infection surveillance system in Jordan, January 2008–February 2014",http://dx.doi.org/10.1111/irv.12354,PMC4746565,26505620,CC BY,"BACKGROUND: Acute respiratory infections (ARIs) are a major cause of morbidity and mortality worldwide. Influenza typically contributes substantially to the burden of ARI, but only limited data are available on influenza activity and seasonality in Jordan. METHODS: Syndromic case definitions were used to identify individuals with severe acute respiratory infections (SARI) admitted to four sentinel hospitals in Jordan. Demographic and clinical data were collected. Nasopharyngeal and oropharyngeal swabs were tested for influenza using real‐time reverse transcription polymerase chain reaction and typed as influenza A or B, with influenza A further subtyped. RESULTS: From January 2008–February 2014, 2891 SARI cases were tested for influenza, and 257 (9%) were positive. While 73% of all SARI cases were under 5 years of age, only 57% of influenza‐positive cases were under 5 years of age. Eight (3%) influenza‐positive cases died. An annual seasonal pattern of influenza activity was observed. The proportion of influenza‐positive cases peaked during November–January (14–42%) in the non‐pandemic years. CONCLUSIONS: Influenza is associated with substantial morbidity and mortality in Jordan. The seasonal pattern of influenza aligns with known Northern Hemisphere seasonality. Further characterization of the clinical and financial burden of influenza in Jordan will be critical in supporting decisions regarding disease control activities.",2016 Mar 29,"['Al‐Abdallat, Mohammad', 'Dawson, Patrick', 'Haddadin, Aktham Jeries', 'El‐Shoubary, Waleed', 'Dueger, Erica', 'Al‐Sanouri, Tarek', 'Said, Mayar M.', 'Talaat, Maha']",Influenza Other Respir Viruses,,,True
e53bab2c782aab7911dc57e4ecf3759a1755fb21,PMC,Porcine aminopeptidase N binds to F4(+) enterotoxigenic Escherichia coli fimbriae,http://dx.doi.org/10.1186/s13567-016-0313-5,PMC4746772,26857562,CC BY,"F4(+) enterotoxigenic Escherichia coli (ETEC) strains cause diarrheal disease in neonatal and post-weaned piglets. Several different host receptors for F4 fimbriae have been described, with porcine aminopeptidase N (APN) reported most recently. The FaeG subunit is essential for the binding of the three F4 variants to host cells. Here we show in both yeast two-hybrid and pulldown assays that APN binds directly to FaeG, the major subunit of F4 fimbriae, from three serotypes of F4(+) ETEC. Modulating APN gene expression in IPEC-J2 cells affected ETEC adherence. Antibodies raised against APN or F4 fimbriae both reduced ETEC adherence. Thus, APN mediates the attachment of F4(+)E. coli to intestinal epithelial cells.",2016 Feb 9,"['Xia, Pengpeng', 'Wang, Yiting', 'Zhu, Congrui', 'Zou, Yajie', 'Yang, Ying', 'Liu, Wei', 'Hardwidge, Philip R.', 'Zhu, Guoqiang']",Vet Res,,,True
ba619ea88290fb57c91eaa57424ff64b0e811f0b,PMC,Identification of Novel Immunogenic Proteins of Neisseria gonorrhoeae by Phage Display,http://dx.doi.org/10.1371/journal.pone.0148986,PMC4747489,26859666,CC BY,"Neisseria gonorrhoeae is one of the most prevalent sexually transmitted diseases worldwide with more than 100 million new infections per year. A lack of intense research over the last decades and increasing resistances to the recommended antibiotics call for a better understanding of gonococcal infection, fast diagnostics and therapeutic measures against N. gonorrhoeae. Therefore, the aim of this work was to identify novel immunogenic proteins as a first step to advance those unresolved problems. For the identification of immunogenic proteins, pHORF oligopeptide phage display libraries of the entire N. gonorrhoeae genome were constructed. Several immunogenic oligopeptides were identified using polyclonal rabbit antibodies against N. gonorrhoeae. Corresponding full-length proteins of the identified oligopeptides were expressed and their immunogenic character was verified by ELISA. The immunogenic character of six proteins was identified for the first time. Additional 13 proteins were verified as immunogenic proteins in N. gonorrhoeae.",2016 Feb 9,"['Connor, Daniel O.', 'Zantow, Jonas', 'Hust, Michael', 'Bier, Frank F.', 'von Nickisch-Rosenegk, Markus']",PLoS One,,,True
8aca747989e024abacecae2fcc95186972c3f5df,PMC,"A herbal formula comprising Rosae Multiflorae Fructus and Lonicerae Japonicae Flos, attenuates collagen-induced arthritis and inhibits TLR4 signalling in rats",http://dx.doi.org/10.1038/srep20042,PMC4748217,26860973,CC BY,"RL, a traditional remedy for Rheumatoid arthritis (RA), comprises two edible herbs, Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. We have reported that RL could inhibit the production of inflammatory mediators in immune cells. Here we investigated the effects and the mechanism of action of RL in collagen-induced arthritis (CIA) rats. RL significantly increased food intake and weight gain of CIA rats without any observable adverse effect; ameliorated joint erythema and swelling; inhibited immune cell infiltration, bone erosion and osteophyte formation in joints; reduced joint protein expression levels of TLR4, phospho-TAK1, phospho-NF-κB p65, phospho-c-Jun and phospho-IRF3; lowered levels of inflammatory factors (TNF-α, IL-6, IL-1β, IL-17A and MCP-1 in sera and TNF-α, IL-6, IL-1β and IL-17A in joints); elevated serum IL-10 level; reinvigorated activities of antioxidant SOD, CAT and GSH-Px in the liver and serum; reduced Th17 cell proportions in splenocytes; inhibited splenocyte proliferation and activation; and lowered serum IgG level. In conclusion, RL at nontoxic doses inhibited TLR4 signaling and potently improved clinical conditions of CIA rats. These findings provide further pharmacological justifications for the traditional use of RL in RA management.",2016 Feb 10,"['Cheng, Brian Chi Yan', 'Yu, Hua', 'Guo, Hui', 'Su, Tao', 'Fu, Xiu-Qiong', 'Li, Ting', 'Cao, Hui-Hui', 'Tse, Anfernee Kai-Wing', 'Wu, Zheng-Zhi', 'Kwan, Hiu-Yee', 'Yu, Zhi-Ling']",Sci Rep,,,True
93799d2647098d29259b8276c712400ccc96f52d,PMC,"A herbal formula comprising Rosae Multiflorae Fructus and Lonicerae Japonicae Flos, attenuates collagen-induced arthritis and inhibits TLR4 signalling in rats",http://dx.doi.org/10.1038/srep20042,PMC4748217,26860973,CC BY,"RL, a traditional remedy for Rheumatoid arthritis (RA), comprises two edible herbs, Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. We have reported that RL could inhibit the production of inflammatory mediators in immune cells. Here we investigated the effects and the mechanism of action of RL in collagen-induced arthritis (CIA) rats. RL significantly increased food intake and weight gain of CIA rats without any observable adverse effect; ameliorated joint erythema and swelling; inhibited immune cell infiltration, bone erosion and osteophyte formation in joints; reduced joint protein expression levels of TLR4, phospho-TAK1, phospho-NF-κB p65, phospho-c-Jun and phospho-IRF3; lowered levels of inflammatory factors (TNF-α, IL-6, IL-1β, IL-17A and MCP-1 in sera and TNF-α, IL-6, IL-1β and IL-17A in joints); elevated serum IL-10 level; reinvigorated activities of antioxidant SOD, CAT and GSH-Px in the liver and serum; reduced Th17 cell proportions in splenocytes; inhibited splenocyte proliferation and activation; and lowered serum IgG level. In conclusion, RL at nontoxic doses inhibited TLR4 signaling and potently improved clinical conditions of CIA rats. These findings provide further pharmacological justifications for the traditional use of RL in RA management.",2016 Feb 10,"['Cheng, Brian Chi Yan', 'Yu, Hua', 'Guo, Hui', 'Su, Tao', 'Fu, Xiu-Qiong', 'Li, Ting', 'Cao, Hui-Hui', 'Tse, Anfernee Kai-Wing', 'Wu, Zheng-Zhi', 'Kwan, Hiu-Yee', 'Yu, Zhi-Ling']",Sci Rep,,,False
02fdaf97dd0af539eada2af2f1563e0d77a28f92,PMC,Discovery of an antibody for pan-ebolavirus therapy,http://dx.doi.org/10.1038/srep20514,PMC4748290,26861827,CC BY,"During the latest outbreak of Ebola virus disease in West Africa, monoclonal antibody therapy (e.g., ZMapp) was utilized to treat patients. However, due to the antigenic differences among the five ebolavirus species, the current therapeutic monoclonal antibodies are only effective against viruses of the species Zaire ebolavirus. Although this particular species has indeed caused the majority of human infections in Central and, recently, West Africa, other ebolavirus species (e.g., Sudan ebolavirus and Bundibugyo ebolavirus) have also repeatedly caused outbreaks in Central Africa and thus should not be neglected in the development of countermeasures against ebolaviruses. Here we report the generation of an ebolavirus glycoprotein-specific monoclonal antibody that effectively inhibits cellular entry of representative isolates of all known ebolavirus species in vitro and show its protective efficacy in mouse models of ebolavirus infections. This novel neutralizing monoclonal antibody targets a highly conserved internal fusion loop in the glycoprotein molecule and prevents membrane fusion of the viral envelope with cellular membranes. The discovery of this highly cross-neutralizing antibody provides a promising option for broad-acting ebolavirus antibody therapy and will accelerate the design of improved vaccines that can selectively elicit cross-neutralizing antibodies against multiple species of ebolaviruses.",2016 Feb 10,"['Furuyama, Wakako', 'Marzi, Andrea', 'Nanbo, Asuka', 'Haddock, Elaine', 'Maruyama, Junki', 'Miyamoto, Hiroko', 'Igarashi, Manabu', 'Yoshida, Reiko', 'Noyori, Osamu', 'Feldmann, Heinz', 'Takada, Ayato']",Sci Rep,,,True
3104d61248ed91506ee62681f924aaa10dadeeb9,PMC,Discovery of an antibody for pan-ebolavirus therapy,http://dx.doi.org/10.1038/srep20514,PMC4748290,26861827,CC BY,"During the latest outbreak of Ebola virus disease in West Africa, monoclonal antibody therapy (e.g., ZMapp) was utilized to treat patients. However, due to the antigenic differences among the five ebolavirus species, the current therapeutic monoclonal antibodies are only effective against viruses of the species Zaire ebolavirus. Although this particular species has indeed caused the majority of human infections in Central and, recently, West Africa, other ebolavirus species (e.g., Sudan ebolavirus and Bundibugyo ebolavirus) have also repeatedly caused outbreaks in Central Africa and thus should not be neglected in the development of countermeasures against ebolaviruses. Here we report the generation of an ebolavirus glycoprotein-specific monoclonal antibody that effectively inhibits cellular entry of representative isolates of all known ebolavirus species in vitro and show its protective efficacy in mouse models of ebolavirus infections. This novel neutralizing monoclonal antibody targets a highly conserved internal fusion loop in the glycoprotein molecule and prevents membrane fusion of the viral envelope with cellular membranes. The discovery of this highly cross-neutralizing antibody provides a promising option for broad-acting ebolavirus antibody therapy and will accelerate the design of improved vaccines that can selectively elicit cross-neutralizing antibodies against multiple species of ebolaviruses.",2016 Feb 10,"['Furuyama, Wakako', 'Marzi, Andrea', 'Nanbo, Asuka', 'Haddock, Elaine', 'Maruyama, Junki', 'Miyamoto, Hiroko', 'Igarashi, Manabu', 'Yoshida, Reiko', 'Noyori, Osamu', 'Feldmann, Heinz', 'Takada, Ayato']",Sci Rep,,,False
78b7a343a9ffffc005daf8a962cf9140f5dc8735,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,True
24098f1320cc2ade94c6bb512d218e9a8b17a92b,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
1bf05553a642185d7561c2d602cae4bd27443da1,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
477e78bc4f35cdb3cd15bd47a9979f829229cbff,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
e03e5a66cb1095abb7ef2483c15432e37af0a83b,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
169b53d99f650262ddacb0691963b12a419ac24e,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
943d67d2e03c02ac4a13788b20118c92dcc857c0,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
cfa45bbe73a1ed62f2c8d5194881b6a496b2d0c6,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
eefce93d155f312462a786767c8bd6e443685420,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
87b38b6d3186810ad00909c0e2f963214808e4be,PMC,miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1),http://dx.doi.org/10.7717/peerj.1635,PMC4748701,26870610,CC BY,"Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.",2016 Feb 4,"['Zhao, Xiaomin', 'Song, Xiangjun', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Zhao, Zhimin', 'Du, Qian', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",PeerJ,,,False
598afbc9be3b81a14195c3a45e3a4ca580e4958f,PMC,The Hepatitis C Virus-Induced Membranous Web and Associated Nuclear Transport Machinery Limit Access of Pattern Recognition Receptors to Viral Replication Sites,http://dx.doi.org/10.1371/journal.ppat.1005428,PMC4749181,26863439,CC BY,"Hepatitis C virus (HCV) is a positive-strand RNA virus of the Flaviviridae family and a major cause of liver disease worldwide. HCV replicates in the cytoplasm, and the synthesis of viral proteins induces extensive rearrangements of host cell membranes producing structures, collectively termed the membranous web (MW). The MW contains the sites of viral replication and assembly, and we have identified distinct membrane fractions derived from HCV-infected cells that contain replication and assembly complexes enriched for viral RNA and infectious virus, respectively. The complex membrane structure of the MW is thought to protect the viral genome limiting its interactions with cytoplasmic pattern recognition receptors (PRRs) and thereby preventing activation of cellular innate immune responses. Here we show that PRRs, including RIG-I and MDA5, and ribosomes are excluded from viral replication and assembly centers within the MW. Furthermore, we present evidence that components of the nuclear transport machinery regulate access of proteins to MW compartments. We show that the restricted assess of RIG-I to the MW can be overcome by the addition of a nuclear localization signal sequence, and that expression of a NLS-RIG-I construct leads to increased immune activation and the inhibition of viral replication.",2016 Feb 10,"['Neufeldt, Christopher J.', 'Joyce, Michael A.', 'Van Buuren, Nicholas', 'Levin, Aviad', 'Kirkegaard, Karla', 'Gale Jr., Michael', 'Tyrrell, D. Lorne J.', 'Wozniak, Richard W.']",PLoS Pathog,,,True
aa6297e7fd55345b1ef69a2cbbb9629d155580a4,PMC,Development and virucidal activity of a novel alcohol-based hand disinfectant supplemented with urea and citric acid,http://dx.doi.org/10.1186/s12879-016-1410-9,PMC4750209,26864562,CC BY,"BACKGROUND: Hand disinfectants are important for the prevention of virus transmission in the health care system and environment. The development of broad antiviral spectrum hand disinfectants with activity against enveloped and non-enveloped viruses is limited due to a small number of permissible active ingredients able to inactivate viruses. METHODS: A new hand disinfectant was developed based upon 69.39 % w/w ethanol and 3.69 % w/w 2-propanol. Different amounts of citric acid and urea were added in order to create a virucidal claim against poliovirus (PV), adenovirus type 5 (AdV) and polyomavirus SV40 (SV40) as non-enveloped test viruses in the presence of fetal calf serum (FCS) as soil load. The exposure time was fixed to 60 s. RESULTS: With the addition of 2.0 % citric acid and 2.0 % urea an activity against the three test viruses was achieved demonstrating a four log(10) reduction of viral titers. Furthermore, this formulation was able to inactivate PV, AdV, SV40 and murine norovirus (MNV) in quantitative suspension assays according to German and European Guidelines within 60 s creating a virucidal claim. For inactivation of vaccinia virus and bovine viral diarrhea virus 15 s exposure time were needed to demonstrate a 4 log(10) reduction resulting in a claim against enveloped viruses. Additionally, it is the first hand disinfectant passing a carrier test with AdV and MNV. CONCLUSIONS: In conclusion, this new formulation with a low alcohol content, citric acid and urea is capable of inactivating all enveloped and non-enveloped viruses as indicated in current guidelines and thereby contributing as valuable addition to the hand disinfection portfolio.",2016 Feb 11,"['Ionidis, Georgios', 'Hübscher, Judith', 'Jack, Thomas', 'Becker, Britta', 'Bischoff, Birte', 'Todt, Daniel', 'Hodasa, Veronika', 'Brill, Florian H. H.', 'Steinmann, Eike', 'Steinmann, Jochen']",BMC Infect Dis,,,True
e3c22f7e1409db69c1be9a7ae76319405506aaea,PMC,Explaining the geographic spread of emerging epidemics: a framework for comparing viral phylogenies and environmental landscape data,http://dx.doi.org/10.1186/s12859-016-0924-x,PMC4750353,26864798,CC BY,"BACKGROUND: Phylogenetic analysis is now an important tool in the study of viral outbreaks. It can reconstruct epidemic history when surveillance epidemiology data are sparse, and can indicate transmission linkages among infections that may not otherwise be evident. However, a remaining challenge is to develop an analytical framework that can test hypotheses about the effect of environmental variables on pathogen spatial spread. Recent phylogeographic approaches can reconstruct the history of virus dispersal from sampled viral genomes and infer the locations of ancestral infections. Such methods provide a unique source of spatio-temporal information, and are exploited here. RESULTS: We present and apply a new statistical framework that combines genomic and geographic data to test the impact of environmental variables on the mode and tempo of pathogen dispersal during emerging epidemics. First, the spatial history of an emerging pathogen is estimated using standard phylogeographic methods. The inferred dispersal path for each phylogenetic lineage is then assigned a “weight” using environmental data (e.g. altitude, land cover). Next, tests measure the association between each environmental variable and lineage movement. A randomisation procedure is used to assess statistical confidence and we validate this approach using simulated data. We apply our new framework to a set of gene sequences from an epidemic of rabies virus in North American raccoons. We test the impact of six different environmental variables on this epidemic and demonstrate that elevation is associated with a slower rabies spread in a natural population. CONCLUSION: This study shows that it is possible to integrate genomic and environmental data in order to test hypotheses concerning the mode and tempo of virus dispersal during emerging epidemics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-016-0924-x) contains supplementary material, which is available to authorized users.",2016 Feb 11,"['Dellicour, Simon', 'Rose, Rebecca', 'Pybus, Oliver G.']",BMC Bioinformatics,,,True
dce4b37c7dd77b761ad89d62448183f4250d7266,PMC,Optimizing Viral Discovery in Bats,http://dx.doi.org/10.1371/journal.pone.0149237,PMC4750870,26867024,CC BY,"Viral discovery studies in bats have increased dramatically over the past decade, yet a rigorous synthesis of the published data is lacking. We extract and analyze data from 93 studies published between 2007–2013 to examine factors that increase success of viral discovery in bats, and specific trends and patterns of infection across host taxa and viral families. Over the study period, 248 novel viruses from 24 viral families have been described. Using generalized linear models, at a study level we show the number of host species and viral families tested best explained number of viruses detected. We demonstrate that prevalence varies significantly across viral family, specimen type, and host taxonomy, and calculate mean PCR prevalence by viral family and specimen type across all studies. Using a logistic model, we additionally identify factors most likely to increase viral detection at an individual level for the entire dataset and by viral families with sufficient sample sizes. Our analysis highlights major taxonomic gaps in recent bat viral discovery efforts and identifies ways to improve future viral pathogen detection through the design of more efficient and targeted sample collection and screening approaches.",2016 Feb 11,"['Young, Cristin C. W.', 'Olival, Kevin J.']",PLoS One,,,True
05257a2230897ea006b3f68dbf0d71e1e7216f55,PMC,"Long-Term Shedding of Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus and Nosocomial Epidemiology in Patients with Hematological Disorders",http://dx.doi.org/10.1371/journal.pone.0148258,PMC4750950,26866481,CC BY,"Respiratory viruses are a cause of upper respiratory tract infections (URTI), but can be associated with severe lower respiratory tract infections (LRTI) in immunocompromised patients. The objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (RSV) and the duration of viral shedding in hematological patients. Nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and RSV on admission as well as on development of respiratory symptoms. Consecutive swabs were collected until viral clearance. Out of 672 tested patients, a total of 111 patients (17%) were infected with one of the investigated viral agents: 40 with influenza, 13 with parainfluenza and 64 with RSV; six patients had influenza/RSV or parainfluenza/RSV co-infections. The majority of infected patients (n = 75/111) underwent stem cell transplantation (42 autologous, 48 allogeneic, 15 autologous and allogeneic). LRTI was observed in 48 patients, of whom 15 patients developed severe LRTI, and 13 patients with respiratory tract infection died. Phylogenetic analysis revealed a variety of influenza A(H1N1)pdm09, A(H3N2), influenza B, parainfluenza 3 and RSV A, B viruses. RSV A was detected in 54 patients, RSV B in ten patients. The newly emerging RSV A genotype ON1 predominated in the study cohort and was found in 48 (75%) of 64 RSV-infected patients. Furthermore, two distinct clusters were detected for RSV A genotype ON1, identical RSV G gene sequences in these patients are consistent with nosocomial transmission. Long-term viral shedding for more than 30 days was significantly associated with prior allogeneic transplantation (p = 0.01) and was most pronounced in patients with RSV infection (n = 16) with a median duration of viral shedding for 80 days (range 35–334 days). Long-term shedding of respiratory viruses might be a catalyzer of nosocomial transmission and must be considered for efficient infection control in immunocompromised patients.",2016 Feb 11,"['Lehners, Nicola', 'Tabatabai, Julia', 'Prifert, Christiane', 'Wedde, Marianne', 'Puthenparambil, Joe', 'Weissbrich, Benedikt', 'Biere, Barbara', 'Schweiger, Brunhilde', 'Egerer, Gerlinde', 'Schnitzler, Paul']",PLoS One,,,True
08b862f9103eb1590d60bd0312f750729b3f2c7d,PMC,Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection,http://dx.doi.org/10.1371/journal.pone.0146599,PMC4752219,26872131,CC BY,"BACKGROUND: The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques. METHODS: A prospective multicenter study (GENDRES-network) was conducted between 2011–2013 in children under the age of two admitted to hospital because of an ARI. Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures. RESULTS: 66 children with positive RSV respiratory illness were included. In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2). In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients. There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P-value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007). CONCLUSION: Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases.",2016 Feb 12,"['Cebey-López, Miriam', 'Pardo-Seco, Jacobo', 'Gómez-Carballa, Alberto', 'Martinón-Torres, Nazareth', 'Martinón-Sánchez, José María', 'Justicia-Grande, Antonio', 'Rivero-Calle, Irene', 'Pinnock, Elli', 'Salas, Antonio', 'Fink, Colin', 'Martinón-Torres, Federico', None]",PLoS One,,,True
743035cdbb5b95039bcf2297eecef6e2de640946,PMC,A Rapid and Low-Cost PCR Thermal Cycler for Infectious Disease Diagnostics,http://dx.doi.org/10.1371/journal.pone.0149150,PMC4752298,26872358,CC BY,"The ability to make rapid diagnosis of infectious diseases broadly available in a portable, low-cost format would mark a great step forward in global health. Many molecular diagnostic assays are developed based on using thermal cyclers to carry out polymerase chain reaction (PCR) and reverse-transcription PCR for DNA and RNA amplification and detection, respectively. Unfortunately, most commercial thermal cyclers are expensive and need continuous electrical power supply, so they are not suitable for uses in low-resource settings. We have previously reported a low-cost and simple approach to amplify DNA using vacuum insulated stainless steel thermoses food cans, which we have named it thermos thermal cycler or TTC. Here, we describe the use of an improved set up to enable the detection of viral RNA targets by reverse-transcription PCR (RT-PCR), thus expanding the TTC’s ability to identify highly infectious, RNA virus-based diseases in low resource settings. The TTC was successful in demonstrating high-speed and sensitive detection of DNA or RNA targets of sexually transmitted diseases, HIV/AIDS, Ebola hemorrhagic fever, and dengue fever. Our innovative TTC costs less than $200 to build and has a capacity of at least eight tubes. In terms of speed, the TTC’s performance exceeded that of commercial thermal cyclers tested. When coupled with low-cost endpoint detection technologies such as nucleic acid lateral-flow assay or a cell-phone-based fluorescence detector, the TTC will increase the availability of on-site molecular diagnostics in low-resource settings.",2016 Feb 12,"['Chan, Kamfai', 'Wong, Pui-Yan', 'Yu, Peter', 'Hardick, Justin', 'Wong, Kah-Yat', 'Wilson, Scott A.', 'Wu, Tiffany', 'Hui, Zoe', 'Gaydos, Charlotte', 'Wong, Season S.']",PLoS One,,,True
ad60294d191a68f9db374d7ec49f42c2303b3b00,PMC,Hepatitis C Virus Resistance to Carbohydrate-Binding Agents,http://dx.doi.org/10.1371/journal.pone.0149064,PMC4752358,26871442,CC BY,"Carbohydrate binding agents (CBAs), including natural lectins, are more and more considered as broad-spectrum antivirals. These molecules are able to directly inhibit many viruses such as Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Dengue Virus, Ebola Virus or Severe Acute Respiratory Syndrome Coronavirus through binding to envelope protein N-glycans. In the case of HIV, it has been shown that CBAs select for mutant viruses with N-glycosylation site deletions which are more sensitive to neutralizing antibodies. In this study we aimed at evaluating the HCV resistance to CBAs in vitro. HCV was cultivated in the presence of increasing Galanthus nivalis agglutinin (GNA), Cyanovirin-N, Concanavalin-A or Griffithsin concentrations, during more than eight weeks. At the end of lectin exposure, the genome of the isolated strains was sequenced and several potential resistance mutations in the E1E2 envelope glycoproteins were identified. The effect of these mutations on viral fitness as well as on sensitivity to inhibition by lectins, soluble CD81 or the 3/11 neutralizing antibody was assessed. Surprisingly, none of these mutations, alone or in combination, conferred resistance to CBAs. In contrast, we observed that some mutants were more sensitive to 3/11 or CD81-LEL inhibition. Additionally, several mutations were identified in the Core and the non-structural proteins. Thus, our results suggest that in contrast to HIV, HCV resistance to CBAs is not directly conferred by mutations in the envelope protein genes but could occur through an indirect mechanism involving mutations in other viral proteins. Further investigations are needed to completely elucidate the underlying mechanisms.",2016 Feb 12,"['Izquierdo, Laure', 'Oliveira, Catarina', 'Fournier, Carole', 'Descamps, Véronique', 'Morel, Virginie', 'Dubuisson, Jean', 'Brochot, Etienne', 'Francois, Catherine', 'Castelain, Sandrine', 'Duverlie, Gilles', 'Helle, Francois']",PLoS One,,,True
2c2c2d6a805a6ea5cdd4568c9bedeedc705e1043,PMC,Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages,http://dx.doi.org/10.1371/journal.pone.0149050,PMC4752512,26872335,CC BY,"Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalysing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. To this end, we studied IRG1 expression in human immune cells under different inflammatory stimuli, such as TNFα and IFNγ, in addition to lipopolysaccharides. Under these conditions, as previously shown in mouse macrophages, IRG1/CAD accumulates in mitochondria. Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Using a synergistic approach of both computational and experimental methods, we here shed more light on the transcriptional machinery of IRG1 expression and could pave the way to therapeutic approaches targeting itaconic acid levels.",2016 Feb 12,"['Tallam, Aravind', 'Perumal, Thaneer M.', 'Antony, Paul M.', 'Jäger, Christian', 'Fritz, Joëlle V.', 'Vallar, Laurent', 'Balling, Rudi', 'del Sol, Antonio', 'Michelucci, Alessandro']",PLoS One,,,True
a8c077a7cfb866ed4ad64e152568313e586ca77d,PMC,Dipeptidyl peptidase-4 and kidney fibrosis in diabetes,http://dx.doi.org/10.1186/s13069-016-0038-0,PMC4752740,26877767,CC BY,"Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease worldwide and is associated with increased morbidity and mortality in patients with both type 1 and type 2 diabetes. Recent evidence revealed that dipeptidyl peptidase-4 (DPP-4) inhibitors may exhibit a protective effect against DN. In fact, the kidney is the organ where the DPP-4 activity is the highest level per organ weight. A preclinical analysis revealed that DPP-4 inhibitors also ameliorated kidney fibrosis. In this review, we analyzed recent reports in this field and explore the renoprotective effects and possible mechanism of the DPP-4 inhibitors.",2016 Feb 13,"['Shi, Sen', 'Koya, Daisuke', 'Kanasaki, Keizo']",Fibrogenesis Tissue Repair,,,True
51e85d19c2cec68dfff68624118086ec2bb6de73,PMC,Scientific Collaborations: How Do We Measure the Return on Relationships?,http://dx.doi.org/10.3389/fpubh.2016.00009,PMC4753292,26913278,CC BY,"Emerging infectious diseases (EIDs), the majority of which are zoonotic, represent a tremendous challenge for public health and biosurveillance infrastructure across the globe. Due to the complexity of zoonotic pathogens, it is essential that research and response to EIDs be a transdisciplinary effort. And while crisis and circumstance may be the initial catalyst for responding to an outbreak, we provide examples of how transdisciplinary scientific collectives, which are organized and solidified in advance of crises, can transform the way the world responds to outbreaks and in some cases could even prevent one from occurring (1). Current methods for assessing whether a cooperative engagement between countries is producing measurable and sustainable value is based on the ideas of return on investment and do not consider the inherent importance of relationships. In this article, we apply the idea of return on relationships (ROR) and propose a method for measuring ROR, using a system dynamics modeling framework commonly used in epidemiology. Tracking the numerous and diverse scientific collaborations that emerged from a training workshop for biosurveillance of bats held in Singapore in 2014, we apply a methodology for visualizing and measuring the relationship networks and outcomes that result. Additionally, the collaborative, multidisciplinary network that coalesced in response to the Hantavirus outbreak in New Mexico is 1993 is discussed as an example of the long-term benefits of ROR.",2016 Feb 15,"['Fair, Jeanne M.', 'Stokes, Martha Mangum', 'Pennington, Deana', 'Mendenhall, Ian H.']",Front Public Health,,,True
5f7b5b1f4748ede29130df5606fd51f4820edc20,PMC,Conformational Flexibility of a Short Loop near the Active Site of the SARS-3CLpro is Essential to Maintain Catalytic Activity,http://dx.doi.org/10.1038/srep20918,PMC4754693,26879383,CC BY,"The SARS 3C-like proteinase (SARS-3CLpro), which is the main proteinase of the SARS coronavirus, is essential to the virus life cycle. This enzyme has been shown to be active as a dimer in which only one protomer is active. However, it remains unknown how the dimer structure maintains an active monomer conformation. It has been observed that the Ser139-Leu141 loop forms a short 3(10)-helix that disrupts the catalytic machinery in the inactive monomer structure. We have tried to disrupt this helical conformation by mutating L141 to T in the stable inactive monomer G11A/R298A/Q299A. The resulting tetra-mutant G11A/L141T/R298A/Q299A is indeed enzymatically active as a monomer. Molecular dynamics simulations revealed that the L141T mutation disrupts the 3(10)-helix and helps to stabilize the active conformation. The coil-3(10)-helix conformational transition of the Ser139-Leu141 loop serves as an enzyme activity switch. Our study therefore indicates that the dimer structure can stabilize the active conformation but is not a required structure in the evolution of the active enzyme, which can also arise through simple mutations.",2016 Feb 16,"['Li, Chunmei', 'Teng, Xin', 'Qi, Yifei', 'Tang, Bo', 'Shi, Hailing', 'Ma, Xiaomin', 'Lai, Luhua']",Sci Rep,,,True
95f0f21246953b8b6258cdf4afd61011c32a686f,PMC,Niclosamide inhibits leaf blight caused by Xanthomonas oryzae in rice,http://dx.doi.org/10.1038/srep21209,PMC4754756,26879887,CC BY,"Rice leaf blight, which is caused by the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo), results in huge losses in grain yield. Here, we show that Xoo-induced rice leaf blight is effectively controlled by niclosamide, an oral antihelminthic drug and molluscicide, which also functions as an anti-tumor agent. Niclosamide directly inhibited the growth of the three Xoo strains PXO99, 10208 and K3a. Niclosamide moved long distances from the site of local application to distant rice tissues. Niclosamide also increased the levels of salicylate and induced the expression of defense-related genes such as OsPR1 and OsWRKY45, which suppressed Xoo-induced leaf wilting. Niclosamide had no detrimental effects on vegetative/reproductive growth and yield. These combined results indicate that niclosamide can be used to block bacterial leaf blight in rice with no negative side effects.",2016 Feb 16,"['Kim, Sung-Il', 'Song, Jong Tae', 'Jeong, Jin-Yong', 'Seo, Hak Soo']",Sci Rep,,,True
7dad7185f2f7dd28cfaa251822682e46bb5b26e6,PMC,"Fugong virus, a novel hantavirus harbored by the small oriental vole (Eothenomys eleusis) in China",http://dx.doi.org/10.1186/s12985-016-0483-9,PMC4754816,26880191,CC BY,"BACKGROUND: Rodents are natural reservoirs of hantaviruses, which cause two disease types: hemorrhagic fever with renal syndrome in Eurasia and hantavirus pulmonary syndrome in North America. Hantaviruses related human cases have been observed throughout Asia, Europe, Africa, and North America. To date, 23 distinct species of hantaviruses, hosted by reservoir, have been identified. However, the diversity and number of hantaviruses are likely underestimated in China, and hantavirus species that cause disease in many regions, including Yunnan province, are unknown. RESULTS: In August 2012, we collected tissue samples from 189 captured animals, including 15 species belonging to 10 genera, 5 families, and 4 orders in Fugong county, Yunnan province, China. Seven species were positive for hantavirus: Eothenomys eleusis (42/94), Apodemus peninsulae (3/25), Niviventer eha (3/27), Cryptotis montivaga (2/8), Anourosorex squamipes (1/1), Sorex araneus (1/1), and Mustela sibirica (1/2). We characterized one full-length genomic sequence of the virus (named fugong virus, FUGV) from a small oriental vole (Eothenomys eleusis). The full-length sequences of the small, medium, and large segments of FUGV were 1813, 3630, and 6531 nt, respectively. FUGV was most closely related to hantavirus LX309, a previously reported species detected in the red-backed vole in Luxi county, Yunnan province, China. However, the amino acid sequences of nucleocapsid (N), glycoprotein (G), and large protein (L) were highly divergent from those of Hantavirus LX309, with amino acid differences of 11.2, 15.3, and 12.7 %, respectively. In phylogenetic trees, FUGV clustered in the lineage corresponding to hantaviruses carried by rodents in the subfamily Arvicolinae. CONCLUSIONS: High prevalence of hantavirus infection in small mammals was found in Fugong county, Yunnan province, China. A novel hantavirus species FUGV was identified from the small oriental vole. This virus is phylogenetic clustering with another hantavirus LX309, but shows highly genomic divergence.",2016 Feb 16,"['Ge, Xing-Yi', 'Yang, Wei-Hong', 'Pan, Hong', 'Zhou, Ji-Hua', 'Han, Xi', 'Zhu, Guang-Jian', 'Desmond, James S.', 'Daszak, Peter', 'Shi, Zheng-Li', 'Zhang, Yun-Zhi']",Virol J,,,True
8e3f518b27782ac9cc19e7556d74100ff23d972b,PMC,Porcine parvovirus infection activates mitochondria-mediated apoptotic signaling pathway by inducing ROS accumulation,http://dx.doi.org/10.1186/s12985-016-0480-z,PMC4755023,26880103,CC BY,"BACKGROUND: Porcine parvovirus (PPV) infection primarily causes reproductive failure of pregnant swine and results in host cell death. Boars, as an important disseminator, shed PPV to sows via semen. PPV infects and numerously replicates in boar testicle, which results in damage of swine testicle in vivo. Reactive oxygen species (ROS), a mediator of cell apoptosis, play a crucial role in the mitochondria apoptotic pathway. However, whether PPV infection induces ST cells apoptosis and ROS accumulation is still unclear. METHODS: To determine the effects of PPV infection on the apoptosis, we detected morphological changes, DNA ladder, activities of caspases, and expression of PARP in PPV-infected ST cells. Moreover, aiming to investigate the effect of PPV infection on the mitochondrial apoptotic pathway and ROS accumulation, we detected the Δψm, apoptosis-related genes, and ROS. To investigate the role of ROS in the process of PPV-induced apoptosis, the ST cells were infected with PPV and treated with the ROS antioxidants. The ROS level was measured using Reactive Oxygen Species Assay Kit and the Δψm, expression level of Bcl-2, translocation of Bax, and redistribution of mitochondria cytochrome c were tested. RESULTS: In this study, we demonstrated that PPV infection could induce apoptosis that was characterized by morphological changes, DNA fragmentation and activation of caspases. Moreover, PPV infection suppressed Bcl-2 expression, enhanced Bax expression and translocation to mitochondria, decreased the mitochondrial transmembrane potential, and triggered the release of cytochrome c, which caused the subsequent activation of caspase-9 and caspase-3 and initiation of apoptosis. However, during the process of PPV-induced apoptosis, the protein levels of Fas and FasL were not affected. Further studies showed that PPV infection caused ROS accumulation. Inhibition of ROS could reduce mitochondrial transmembrane potential and could significantly block ST cells apoptosis via suppressing Bax translocation, cytochrome c and caspase-3 activation. CONCLUSIONS: All these results suggest that PPV-induced ROS accumulation mediates apoptosis in ST cells, which provided theoretical basis for the molecular pathogenesis of PPV infection.",2016 Feb 16,"['Zhao, Xiaomin', 'Xiang, Hailing', 'Bai, Xiaoyuan', 'Fei, Naijiao', 'Huang, Yong', 'Song, Xiangjun', 'Zhang, Hongling', 'Zhang, Liang', 'Tong, Dewen']",Virol J,,,True
38bed8a14f2f6103cf5f8ddc6db772c8ab52f7c4,PMC,Pathogenesis and Diagnostic Approaches of Avian Infectious Bronchitis,http://dx.doi.org/10.1155/2016/4621659,PMC4756178,26955391,CC BY,"Infectious bronchitis (IB) is one of the major economically important poultry diseases distributed worldwide. It is caused by infectious bronchitis virus (IBV) and affects both galliform and nongalliform birds. Its economic impact includes decreased egg production and poor egg quality in layers, stunted growth, poor carcass weight, and mortality in broiler chickens. Although primarily affecting the respiratory tract, IBV demonstrates a wide range of tissues tropism, including the renal and reproductive systems. Thus, disease outcome may be influenced by the organ or tissue involved as well as pathotypes or strain of the infecting virus. Knowledge on the epidemiology of the prevalent IBV strains in a particular region is therefore important to guide control and preventions. Meanwhile previous diagnostic methods such as serology and virus isolations are less sensitive and time consuming, respectively; current methods, such as reverse transcription polymerase chain reaction (RT-PCR), Restriction Fragment Length Polymorphism (RFLP), and sequencing, offer highly sensitive, rapid, and accurate diagnostic results, thus enabling the genotyping of new viral strains within the shortest possible time. This review discusses aspects on pathogenesis and diagnostic methods for IBV infection.",2016 Feb 3,"['Bande, Faruku', 'Arshad, Siti Suri', 'Omar, Abdul Rahman', 'Bejo, Mohd Hair', 'Abubakar, Muhammad Salisu', 'Abba, Yusuf']",Adv Virol,,,True
4589d4013cf69c396e0fdb67131022fc11119654,PMC,Association between the Severity of Influenza A(H7N9) Virus Infections and Length of the Incubation Period,http://dx.doi.org/10.1371/journal.pone.0148506,PMC4757028,26885816,CC BY,"BACKGROUND: In early 2013, a novel avian-origin influenza A(H7N9) virus emerged in China, and has caused sporadic human infections. The incubation period is the delay from infection until onset of symptoms, and varies from person to person. Few previous studies have examined whether the duration of the incubation period correlates with subsequent disease severity. METHODS AND FINDINGS: We analyzed data of period of exposure on 395 human cases of laboratory-confirmed influenza A(H7N9) virus infection in China in a Bayesian framework using a Weibull distribution. We found a longer incubation period for the 173 fatal cases with a mean of 3.7 days (95% credibility interval, CrI: 3.4–4.1), compared to a mean of 3.3 days (95% CrI: 2.9–3.6) for the 222 non-fatal cases, and the difference in means was marginally significant at 0.47 days (95% CrI: -0.04, 0.99). There was a statistically significant correlation between a longer incubation period and an increased risk of death after adjustment for age, sex, geographical location and underlying medical conditions (adjusted odds ratio 1.70 per day increase in incubation period; 95% credibility interval 1.47–1.97). CONCLUSIONS: We found a significant association between a longer incubation period and a greater risk of death among human H7N9 cases. The underlying biological mechanisms leading to this association deserve further exploration.",2016 Feb 17,"['Virlogeux, Victor', 'Yang, Juan', 'Fang, Vicky J.', 'Feng, Luzhao', 'Tsang, Tim K.', 'Jiang, Hui', 'Wu, Peng', 'Zheng, Jiandong', 'Lau, Eric H. Y.', 'Qin, Ying', 'Peng, Zhibin', 'Peiris, J. S. Malik', 'Yu, Hongjie', 'Cowling, Benjamin J.']",PLoS One,,,True
00326efcca0852dc6e39dc6b7786267e1bc4f194,PMC,"A Review of Pediatric Critical Care in Resource-Limited Settings: A Look at Past, Present, and Future Directions",http://dx.doi.org/10.3389/fped.2016.00005,PMC4757646,26925393,CC BY,"Fifteen years ago, United Nations world leaders defined millenium development goal 4 (MDG 4): to reduce under-5-year mortality rates by two-thirds by the year 2015. Unfortunately, only 27 of 138 developing countries are expected to achieve MDG 4. The majority of childhood deaths in these settings result from reversible causes, and developing effective pediatric emergency and critical care services could substantially reduce this mortality. The Ebola outbreak highlighted the fragility of health care systems in resource-limited settings and emphasized the urgent need for a paradigm shift in the global approach to healthcare delivery related to critical illness. This review provides an overview of pediatric critical care in resource-limited settings and outlines strategies to address challenges specific to these areas. Implementation of these tools has the potential to move us toward delivery of an adequate standard of critical care for all children globally, and ultimately decrease global child mortality in resource-limited settings.",2016 Feb 18,"['Turner, Erin L.', 'Nielsen, Katie R.', 'Jamal, Shelina M.', 'von Saint André-von Arnim, Amelie', 'Musa, Ndidiamaka L.']",Front Pediatr,,,True
77fc830cd32e8b07cd22a11a8d519f9d35f7d7ff,PMC,Effects of memory on the shapes of simple outbreak trees,http://dx.doi.org/10.1038/srep21159,PMC4758066,26888437,CC BY,"Genomic tools, including phylogenetic trees derived from sequence data, are increasingly used to understand outbreaks of infectious diseases. One challenge is to link phylogenetic trees to patterns of transmission. Particularly in bacteria that cause chronic infections, this inference is affected by variable infectious periods and infectivity over time. It is known that non-exponential infectious periods can have substantial effects on pathogens’ transmission dynamics. Here we ask how this non-Markovian nature of an outbreak process affects the branching trees describing that process, with particular focus on tree shapes. We simulate Crump-Mode-Jagers branching processes and compare different patterns of infectivity over time. We find that memory (non-Markovian-ness) in the process can have a pronounced effect on the shapes of the outbreak’s branching pattern. However, memory also has a pronounced effect on the sizes of the trees, even when the duration of the simulation is fixed. When the sizes of the trees are constrained to a constant value, memory in our processes has little direct effect on tree shapes, but can bias inference of the birth rate from trees. We compare simulated branching trees to phylogenetic trees from an outbreak of tuberculosis in Canada, and discuss the relevance of memory to this dataset.",2016 Feb 18,"['Plazzotta, Giacomo', 'Kwan, Christopher', 'Boyd, Michael', 'Colijn, Caroline']",Sci Rep,,,True
4d7b3ed96d9a6f56840f5a3b47aac5fb24999635,PMC,Effects of memory on the shapes of simple outbreak trees,http://dx.doi.org/10.1038/srep21159,PMC4758066,26888437,CC BY,"Genomic tools, including phylogenetic trees derived from sequence data, are increasingly used to understand outbreaks of infectious diseases. One challenge is to link phylogenetic trees to patterns of transmission. Particularly in bacteria that cause chronic infections, this inference is affected by variable infectious periods and infectivity over time. It is known that non-exponential infectious periods can have substantial effects on pathogens’ transmission dynamics. Here we ask how this non-Markovian nature of an outbreak process affects the branching trees describing that process, with particular focus on tree shapes. We simulate Crump-Mode-Jagers branching processes and compare different patterns of infectivity over time. We find that memory (non-Markovian-ness) in the process can have a pronounced effect on the shapes of the outbreak’s branching pattern. However, memory also has a pronounced effect on the sizes of the trees, even when the duration of the simulation is fixed. When the sizes of the trees are constrained to a constant value, memory in our processes has little direct effect on tree shapes, but can bias inference of the birth rate from trees. We compare simulated branching trees to phylogenetic trees from an outbreak of tuberculosis in Canada, and discuss the relevance of memory to this dataset.",2016 Feb 18,"['Plazzotta, Giacomo', 'Kwan, Christopher', 'Boyd, Michael', 'Colijn, Caroline']",Sci Rep,,,False
d54725b7c8072e09a2498c8f2ce1e7ee7839eaf6,PMC,"Complete Genome Sequence of a Porcine Epidemic Diarrhea Virus Strain from Vietnam, HUA-14PED96, with a Large Genomic Deletion",http://dx.doi.org/10.1128/genomeA.00002-16,PMC4759056,26893409,CC BY,"A highly virulent strain of Porcine epidemic diarrhea virus (PEDV) causing severe diarrhea has recently emerged in Vietnam. Genomic sequences from a novel strain, HUA-14PED96, isolated from a Vietnamese piglet with serious diarrhea show relatively high identity with U.S.-like PEDV strains, and have a 72-nt deletion in the open reading frame 1a (ORF1a) gene.",2016 Feb 18,"['Choe, Se-Eun', 'Park, Kee-Hwan', 'Lim, Seong-In', 'Le, Van Phan', 'Hien, Nguyen Ba', 'Thach, Pham Ngoc', 'Phuong, Le Huynh Thanh', 'An, Byung-Hyun', 'Han, Song Hee', 'Cho, In-Soo', 'An, Dong-Jun']",Genome Announc,,,True
882f40d2ce4eceeb438b59e25e2e023fb5e169ba,PMC,"Impact of Influenza on Outpatient Visits, Hospitalizations, and Deaths by Using a Time Series Poisson Generalized Additive Model",http://dx.doi.org/10.1371/journal.pone.0149468,PMC4760679,26894876,CC BY,"BACKGROUND: The disease burden associated with influenza in developing tropical and subtropical countries is poorly understood owing to the lack of a comprehensive disease surveillance system and information-exchange mechanisms. The impact of influenza on outpatient visits, hospital admissions, and deaths has not been fully demonstrated to date in south China. METHODS: A time series Poisson generalized additive model was used to quantitatively assess influenza-like illness (ILI) and influenza disease burden by using influenza surveillance data in Zhuhai City from 2007 to 2009, combined with the outpatient, inpatient, and respiratory disease mortality data of the same period. RESULTS: The influenza activity in Zhuhai City demonstrated a typical subtropical seasonal pattern; however, each influenza virus subtype showed a specific transmission variation. The weekly ILI case number and virus isolation rate had a very close positive correlation (r = 0.774, P < 0.0001). The impact of ILI and influenza on weekly outpatient visits was statistically significant (P < 0.05). We determined that 10.7% of outpatient visits were associated with ILI and 1.88% were associated with influenza. ILI also had a significant influence on the hospitalization rates (P < 0.05), but mainly in populations <25 years of age. No statistically significant effect of influenza on hospital admissions was found (P > 0.05). The impact of ILI on chronic obstructive pulmonary disease (COPD) was most significant (P < 0.05), with 33.1% of COPD-related deaths being attributable to ILI. The impact of influenza on the mortality rate requires further evaluation. CONCLUSIONS: ILI is a feasible indicator of influenza activity. Both ILI and influenza have a large impact on outpatient visits. Although ILI affects the number of hospital admissions and deaths, we found no consistent influence of influenza, which requires further assessment.",2016 Feb 19,"['Guo, Ru-ning', 'Zheng, Hui-zhen', 'Ou, Chun-quan', 'Huang, Li-qun', 'Zhou, Yong', 'Zhang, Xin', 'Liang, Can-kun', 'Lin, Jin-yan', 'Zhong, Hao-jie', 'Song, Tie', 'Luo, Hui-ming']",PLoS One,,,True
4a94f3fe57da5dad4c965d59faf0facc2039175a,PMC,Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines,http://dx.doi.org/10.1371/journal.pone.0149364,PMC4760941,26895072,CC0,"The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA-vectored vaccines inoculated by scarification can elicit protective immune responses that are comparable to subcutaneous vaccination, and may allow for antigen sparing when vaccine supply is limited.",2016 Feb 19,"['Meseda, Clement A.', 'Atukorale, Vajini', 'Kuhn, Jordan', 'Schmeisser, Falko', 'Weir, Jerry P.']",PLoS One,,,True
f3869eb49905ee75dbd6acd2964cb74f69154b2a,PMC,Virus replicon particles expressing porcine reproductive and respiratory syndrome virus proteins elicit immune priming but do not confer protection from viremia in pigs,http://dx.doi.org/10.1186/s13567-016-0318-0,PMC4761149,26895704,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of one of the most devastating and economically significant viral disease of pigs worldwide. The vaccines currently available on the market elicit only limited protection. Recombinant vesicular stomatitis virus (VSV) replicon particles (VRP) have been used successfully to induce protection against influenza A virus (IAV) in chickens and bluetongue virus in sheep. In this study, VSV VRP expressing the PRRSV envelope proteins GP5, M, GP4, GP3, GP2 and the nucleocapsid protein N, individually or in combination, were generated and evaluated as a potential vector vaccine against PRRSV infection. High level expression of the recombinant PRRSV proteins was demonstrated in cell culture. However, none of the PRRSV antigens expressed from VRP, with the exception of the N protein, did induce any detectable antibody response in pigs before challenge infection with PRRSV. After challenge however, the antibody responses against GP5, GP4 and GP3 appeared in average 2 weeks earlier than in pigs vaccinated with the empty control VRP. No reduction of viremia was observed in the vaccinated group compared with the control group. When pigs were co-vaccinated with VRP expressing IAV antigens and VRP expressing PRRSV glycoproteins, only antibody responses to the IAV antigens were detectable. These data show that the VSV replicon vector can induce immune responses to heterologous proteins in pigs, but that the PRRSV envelope proteins expressed from VSV VRP are poorly immunogenic. Nevertheless, they prime the immune system for significantly earlier B-cell responses following PRRSV challenge infection.",2016 Feb 19,"['Eck, Melanie', 'Durán, Margarita García', 'Ricklin, Meret E.', 'Locher, Samira', 'Sarraseca, Javier', 'Rodríguez, María José', 'McCullough, Kenneth C.', 'Summerfield, Artur', 'Zimmer, Gert', 'Ruggli, Nicolas']",Vet Res,,,True
577c6a13f9ef70e9756890fc66e98f537c01ac0a,PMC,Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis),http://dx.doi.org/10.1038/srep21878,PMC4761889,26899616,CC BY,"The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV.",2016 Feb 22,"['Munster, Vincent J.', 'Adney, Danielle R.', 'van Doremalen, Neeltje', 'Brown, Vienna R.', 'Miazgowicz, Kerri L.', 'Milne-Price, Shauna', 'Bushmaker, Trenton', 'Rosenke, Rebecca', 'Scott, Dana', 'Hawkinson, Ann', 'de Wit, Emmie', 'Schountz, Tony', 'Bowen, Richard A.']",Sci Rep,,,True
5e43557663dd87fa5099c9abb009b9a85e3c474f,PMC,Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis),http://dx.doi.org/10.1038/srep21878,PMC4761889,26899616,CC BY,"The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV.",2016 Feb 22,"['Munster, Vincent J.', 'Adney, Danielle R.', 'van Doremalen, Neeltje', 'Brown, Vienna R.', 'Miazgowicz, Kerri L.', 'Milne-Price, Shauna', 'Bushmaker, Trenton', 'Rosenke, Rebecca', 'Scott, Dana', 'Hawkinson, Ann', 'de Wit, Emmie', 'Schountz, Tony', 'Bowen, Richard A.']",Sci Rep,,,False
69129d8f3e4a1c80f2437d16f044e37e43c03f37,PMC,Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses,http://dx.doi.org/10.1038/ncomms10680,PMC4762884,26893169,CC BY,"Stimulator of interferon genes (STING) is known be involved in control of DNA viruses but has an unexplored role in control of RNA viruses. During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon. Here we identify a STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV). Further, IAV interacts with STING through its conserved hemagglutinin fusion peptide (FP). Interestingly, FP antagonizes interferon production induced by membrane fusion or IAV but not by cGAMP or DNA. Similar to the enveloped RNA viruses, membrane fusion stimulates interferon production in a STING-dependent but cGAS-independent manner. Abolishment of this pathway led to reduced interferon production and impaired control of enveloped RNA viruses. Thus, enveloped RNA viruses stimulate a cGAS-independent STING pathway, which is targeted by IAV.",2016 Feb 19,"['Holm, Christian K.', 'Rahbek, Stine H.', 'Gad, Hans Henrik', 'Bak, Rasmus O.', 'Jakobsen, Martin R.', 'Jiang, Zhaozaho', 'Hansen, Anne Louise', 'Jensen, Simon K.', 'Sun, Chenglong', 'Thomsen, Martin K.', 'Laustsen, Anders', 'Nielsen, Camilla G.', 'Severinsen, Kasper', 'Xiong, Yingluo', 'Burdette, Dara L.', 'Hornung, Veit', 'Lebbink, Robert Jan', 'Duch, Mogens', 'Fitzgerald, Katherine A.', 'Bahrami, Shervin', 'Mikkelsen, Jakob Giehm', 'Hartmann, Rune', 'Paludan, Søren R.']",Nat Commun,,,True
7249caf14f73593c88c505809ebfa9dc24e6dbe0,PMC,Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses,http://dx.doi.org/10.1038/ncomms10680,PMC4762884,26893169,CC BY,"Stimulator of interferon genes (STING) is known be involved in control of DNA viruses but has an unexplored role in control of RNA viruses. During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon. Here we identify a STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV). Further, IAV interacts with STING through its conserved hemagglutinin fusion peptide (FP). Interestingly, FP antagonizes interferon production induced by membrane fusion or IAV but not by cGAMP or DNA. Similar to the enveloped RNA viruses, membrane fusion stimulates interferon production in a STING-dependent but cGAS-independent manner. Abolishment of this pathway led to reduced interferon production and impaired control of enveloped RNA viruses. Thus, enveloped RNA viruses stimulate a cGAS-independent STING pathway, which is targeted by IAV.",2016 Feb 19,"['Holm, Christian K.', 'Rahbek, Stine H.', 'Gad, Hans Henrik', 'Bak, Rasmus O.', 'Jakobsen, Martin R.', 'Jiang, Zhaozaho', 'Hansen, Anne Louise', 'Jensen, Simon K.', 'Sun, Chenglong', 'Thomsen, Martin K.', 'Laustsen, Anders', 'Nielsen, Camilla G.', 'Severinsen, Kasper', 'Xiong, Yingluo', 'Burdette, Dara L.', 'Hornung, Veit', 'Lebbink, Robert Jan', 'Duch, Mogens', 'Fitzgerald, Katherine A.', 'Bahrami, Shervin', 'Mikkelsen, Jakob Giehm', 'Hartmann, Rune', 'Paludan, Søren R.']",Nat Commun,,,False
ca96f361ba8d99dedbd1421fe735d230e86f7797,PMC,The Glycoproteins of All Filovirus Species Use the Same Host Factors for Entry into Bat and Human Cells but Entry Efficiency Is Species Dependent,http://dx.doi.org/10.1371/journal.pone.0149651,PMC4762945,26901159,CC BY,"Ebola and marburgviruses, members of the family Filoviridae, can cause severe hemorrhagic fever in humans. The ongoing Ebola virus (EBOV) disease epidemic in Western Africa claimed more than 11,300 lives and was associated with secondary cases outside Africa, demonstrating that filoviruses pose a global health threat. Bats constitute an important natural reservoir of filoviruses, including viruses of the recently identified Cuevavirus genus within the Filoviridae family. However, the interactions of filoviruses with bat cells are incompletely understood. Here, we investigated whether filoviruses employ different strategies to enter human and bat cells. For this, we examined host cell entry driven by glycoproteins (GP) from all filovirus species into cell lines of human and fruit bat origin. We show that all GPs were able to mediate entry into human and most fruit bat cell lines with roughly comparable efficiency. In contrast, the efficiency of entry into the cell line EidNi/41 derived from a straw-colored fruit bat varied markedly between the GPs of different filovirus species. Furthermore, inhibition studies demonstrated that filoviruses employ the same host cell factors for entry into human, non-human primate and fruit bat cell lines, including cysteine proteases, two pore channels and NPC1 (Niemann-Pick C1 molecule). Finally, processing of GP by furin and the presence of the mucin-like domain in GP were dispensable for entry into both human and bat cell lines. Collectively, these results show that filoviruses rely on the same host cell factors for entry into human and fruit bat cells, although the efficiency of the usage of these factors might differ between filovirus species.",2016 Feb 22,"['Hoffmann, Markus', 'González Hernández, Mariana', 'Berger, Elisabeth', 'Marzi, Andrea', 'Pöhlmann, Stefan']",PLoS One,,,True
5ea003777403bda990fe5a2471273b477e529751,PMC,Protective effects of fenofibrate against acute lung injury induced by intestinal ischemia/reperfusion in mice,http://dx.doi.org/10.1038/srep22044,PMC4763198,26902261,CC BY,"This experiment was conducted to evaluate whether pretreatment with fenofibrate could mitigate acute lung injury (ALI) in a mice model of intestinal ischemia/reperfusion (I/R). Male C57BL/6 mice were randomly assigned into three groups (n = 6): sham, intestinal I/R + vehicle, and intestinal I/R + fenofibrate. Intestinal I/R was achieved by clamping the superior mesenteric artery. Fenofibrate (100 mg/kg) or equal volume of vehicle was injected intraperitoneally 60 minutes before the ischemia. At the end of experiment, measurement of pathohistological score, inflammatory mediators and other markers were performed. In addition, a 24-hour survival experiment was conducted in intestinal I/R mice treated with fenofibrate or vehicle. The chief results were as anticipated. Pathohistological evaluation indicated that fenofibrate ameliorated the local intestine damage and distant lung injury. Pretreatment with fenofibrate significantly decreased inflammatory factors in both the intestine and the lung. Consistently, renal creatine levels and hepatic ALT levels were significantly decreased in the fenofibrate group. Moreover, serum systemic inflammatory response indicators were significantly alleviated in the fenofibrate group. In addition, fenofibrate administration significantly improved the survival rate. Collectively, our data indicated that pretreatment with fenofibrate prior to ischemia attenuated intestinal I/R injury and ALI.",2016 Feb 23,"['Zhu, Qiankun', 'He, Guizhen', 'Wang, Jie', 'Wang, Yukang', 'Chen, Wei']",Sci Rep,,,True
de0bb38fe24062ae86287891a21a9851a0e6b7f3,PMC,Delayed Time-to-Treatment of an Antisense Morpholino Oligomer Is Effective against Lethal Marburg Virus Infection in Cynomolgus Macaques,http://dx.doi.org/10.1371/journal.pntd.0004456,PMC4764691,26901785,CC0,"Marburg virus (MARV) is an Ebola-like virus in the family Filovirdae that causes sporadic outbreaks of severe hemorrhagic fever with a case fatality rate as high as 90%. AVI-7288, a positively charged antisense phosphorodiamidate morpholino oligomer (PMOplus) targeting the viral nucleoprotein gene, was evaluated as a potential therapeutic intervention for MARV infection following delayed treatment of 1, 24, 48, and 96 h post-infection (PI) in a nonhuman primate lethal challenge model. A total of 30 cynomolgus macaques were divided into 5 groups of 6 and infected with 1,830 plaque forming units of MARV subcutaneously. AVI-7288 was administered by bolus infusion daily for 14 days at 15 mg/kg body weight. Survival was the primary endpoint of the study. While none (0 of 6) of the saline group survived, 83–100% of infected monkeys survived when treatment was initiated 1, 24, 48, or 96 h post-infection (PI). The antisense treatment also reduced serum viremia and inflammatory cytokines in all treatment groups compared to vehicle controls. The antibody immune response to virus was preserved and tissue viral antigen was cleared in AVI-7288 treated animals. These data show that AVI-7288 protects NHPs against an otherwise lethal MARV infection when treatment is initiated up to 96 h PI.",2016 Feb 22,"['Warren, Travis K.', 'Whitehouse, Chris A.', 'Wells, Jay', 'Welch, Lisa', 'Charleston, Jay S.', 'Heald, Alison', 'Nichols, Donald K.', 'Mattix, Marc E.', 'Palacios, Gustavo', 'Kugleman, Jeffrey R.', 'Iversen, Patrick L.', 'Bavari, Sina']",PLoS Negl Trop Dis,,,True
9915073ee985307fd682c4df24810387ae83c338,PMC,RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines,http://dx.doi.org/10.1186/s12885-016-2197-1,PMC4765116,26911141,CC BY,"BACKGROUND: Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced “RNA disruption” is, the extent to which it is associated with drug response or what the underlying mechanisms are. METHODS: Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. RESULTS: All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3’-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. CONCLUSIONS: Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues and is associated with drug response. Although present, the link between apoptosis and RNA disruption is not completely understood. Evaluation of RNA disruption is thus proposed as a novel and effective biomarker to assess response to chemotherapy drugs in vitro and in vivo. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2197-1) contains supplementary material, which is available to authorized users.",2016 Feb 24,"['Narendrula, Rashmi', 'Mispel-Beyer, Kyle', 'Guo, Baoqing', 'Parissenti, Amadeo M.', 'Pritzker, Laura B.', 'Pritzker, Ken', 'Masilamani, Twinkle', 'Wang, Xiaohui', 'Lannér, Carita']",BMC Cancer,,,True
0df2a9766ade17a0d9a625ef02722fc167ee0526,PMC,Truncation of C-terminal 20 amino acids in PA-X contributes to adaptation of swine influenza virus in pigs,http://dx.doi.org/10.1038/srep21845,PMC4766433,26912401,CC BY,"The PA-X protein is a fusion protein incorporating the N-terminal 191 amino acids of the PA protein with a short C-terminal sequence encoded by an overlapping ORF (X-ORF) in segment 3 that is accessed by + 1 ribosomal frameshifting, and this X-ORF exists in either full length or a truncated form (either 61-or 41-condons). Genetic evolution analysis indicates that all swine influenza viruses (SIVs) possessed full-length PA-X prior to 1985, but since then SIVs with truncated PA-X have gradually increased and become dominant, implying that truncation of this protein may contribute to the adaptation of influenza virus in pigs. To verify this hypothesis, we constructed PA-X extended viruses in the background of a “triple-reassortment” H1N2 SIV with truncated PA-X, and evaluated their biological characteristics in vitro and in vivo. Compared with full-length PA-X, SIV with truncated PA-X had increased viral replication in porcine cells and swine respiratory tissues, along with enhanced pathogenicity, replication and transmissibility in pigs. Furthermore, we found that truncation of PA-X improved the inhibition of IFN-I mRNA expression. Hereby, our results imply that truncation of PA-X may contribute to the adaptation of SIV in pigs.",2016 Feb 25,"['Xu, Guanlong', 'Zhang, Xuxiao', 'Sun, Yipeng', 'Liu, Qinfang', 'Sun, Honglei', 'Xiong, Xin', 'Jiang, Ming', 'He, Qiming', 'Wang, Yu', 'Pu, Juan', 'Guo, Xin', 'Yang, Hanchun', 'Liu, Jinhua']",Sci Rep,,,True
61c8af64ef0a95e3f6dfc71ced3f94c2768e23d2,PMC,A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses,http://dx.doi.org/10.1038/srep22008,PMC4766503,26911565,CC BY,"A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities.",2016 Feb 25,"['Zhao, Hanjun', 'Zhou, Jie', 'Zhang, Ke', 'Chu, Hin', 'Liu, Dabin', 'Poon, Vincent Kwok-Man', 'Chan, Chris Chung-Sing', 'Leung, Ho-Chuen', 'Fai, Ng', 'Lin, Yong-Ping', 'Zhang, Anna Jin-Xia', 'Jin, Dong-Yan', 'Yuen, Kwok-Yung', 'Zheng, Bo-Jian']",Sci Rep,,,True
94827ed2231500b8b66fde9844d2aebe81a4aba9,PMC,Niclosamide induced cell apoptosis via upregulation of ATF3 and activation of PERK in Hepatocellular carcinoma cells,http://dx.doi.org/10.1186/s12876-016-0442-3,PMC4766699,26917416,CC BY,"BACKGROUND: Hepatocellular carcinoma (HCC) is one of most common and aggressive human malignancies in the world, especially, in eastern Asia, and its mortality is very high at any phase. We want to investigate mechanism of niclosamide inducing cell apoptosis in HCC. METHODS: Two hepatoma cell lines were used to evaluate activity of niclosamide inducing cell apoptosis and study its mechanism. Quantitative real-time PCR and western blotting were used in analysis of genes expression or protein active regulated by niclosamide. RESULTS: Niclosamide remarkably induced cell apoptosis in hepatoma cells. Furthermore, our study revealed that RNA-dependent protein kinase-like kinase (PERK) is activated and its expression is up-regulated in HCC cells which are exposed to niclosamide. niclosamide also significantly increase activating transcription factor 3 (ATF3), activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein-homologous protein (CHOP) expression in HCC cells. It’s suggested that the function of niclosamide was abrogated by PERK inhibitor or absent ATF3. Expression of PERK and CHOP is correlated with ATF3 level in the cells. CONCLUSION: Taken together, our results indicate that ATF3 plays an integral role in ER stress activated and cell apoptosis induced by niclosamide in HCC cells. In this study, the new mechanism of niclosamide as anti-cancer we investigated, too.",2016 Feb 25,"['Weng, Shunyan', 'Zhou, Liang', 'Deng, Qing', 'Wang, Jiaxian', 'Yu, Yan', 'Zhu, Jianwei', 'Yuan, Yunsheng']",BMC Gastroenterol,,,True
1352ae42e48ab6a01c1282db023286ab4e39cbe9,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
c850c2c541b74c1028f99bcf751aae9b1e4a8fc0,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
c3f62bba43fe602e78239d8e8bf60e6c0e1fc008,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
99304ba131e8983452dca5ae9118747496d678a9,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
60ef899f357bb02c4a27dae76a76b3d01f057798,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
19c3185194bafe8e4d966d300b95478a29d32860,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
4f1ad2c0d597b19ba0cf7ce1a8114641876afc84,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
82e2f47ebd6563b442e05f5d247eb187abc87579,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
6e673126a8a28d78c1030b36603d190c1dd47286,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,False
a918e4f69a765616d8708c2267fb54ddb8644409,PMC,"Molecular epidemiology and evolutionary histories of human coronavirus OC43 and HKU1 among patients with upper respiratory tract infections in Kuala Lumpur, Malaysia",http://dx.doi.org/10.1186/s12985-016-0488-4,PMC4766700,26916286,CC BY,"BACKGROUND: Despite the worldwide circulation of human coronavirus OC43 (HCoV-OC43) and HKU1 (HCoV-HKU1), data on their molecular epidemiology and evolutionary dynamics in the tropical Southeast Asia region is lacking. METHODS: The study aimed to investigate the genetic diversity, temporal distribution, population history and clinical symptoms of betacoronavirus infections in Kuala Lumpur, Malaysia between 2012 and 2013. A total of 2,060 adults presented with acute respiratory symptoms were screened for the presence of betacoronaviruses using multiplex PCR. The spike glycoprotein, nucleocapsid and 1a genes were sequenced for phylogenetic reconstruction and Bayesian coalescent inference. RESULTS: A total of 48/2060 (2.4 %) specimens were tested positive for HCoV-OC43 (1.3 %) and HCoV-HKU1 (1.1 %). Both HCoV-OC43 and HCoV-HKU1 were co-circulating throughout the year, with the lowest detection rates reported in the October-January period. Phylogenetic analysis of the spike gene showed that the majority of HCoV-OC43 isolates were grouped into two previously undefined genotypes, provisionally assigned as novel lineage 1 and novel lineage 2. Sign of natural recombination was observed in these potentially novel lineages. Location mapping showed that the novel lineage 1 is currently circulating in Malaysia, Thailand, Japan and China, while novel lineage 2 can be found in Malaysia and China. Molecular dating showed the origin of HCoV-OC43 around late 1950s, before it diverged into genotypes A (1960s), B (1990s), and other genotypes (2000s). Phylogenetic analysis revealed that 27.3 % of the HCoV-HKU1 strains belong to genotype A while 72.7 % belongs to genotype B. The tree root of HCoV-HKU1 was similar to that of HCoV-OC43, with the tMRCA of genotypes A and B estimated around the 1990s and 2000s, respectively. Correlation of HCoV-OC43 and HCoV-HKU1 with the severity of respiratory symptoms was not observed. CONCLUSIONS: The present study reported the molecular complexity and evolutionary dynamics of human betacoronaviruses among adults with acute respiratory symptoms in a tropical country. Two novel HCoV-OC43 genetic lineages were identified, warranting further investigation on their genotypic and phenotypic characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0488-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Al-Khannaq, Maryam Nabiel', 'Ng, Kim Tien', 'Oong, Xiang Yong', 'Pang, Yong Kek', 'Takebe, Yutaka', 'Chook, Jack Bee', 'Hanafi, Nik Sherina', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Virol J,,,True
3846cb057daf0b69fec4d889ff8657d252d94509,PMC,Moving interdisciplinary science forward: integrating participatory modelling with mathematical modelling of zoonotic disease in Africa,http://dx.doi.org/10.1186/s40249-016-0110-4,PMC4766706,26916067,CC BY,"This review outlines the benefits of using multiple approaches to improve model design and facilitate multidisciplinary research into infectious diseases, as well as showing and proposing practical examples of effective integration. It looks particularly at the benefits of using participatory research in conjunction with traditional modelling methods to potentially improve disease research, control and management. Integrated approaches can lead to more realistic mathematical models which in turn can assist with making policy decisions that reduce disease and benefit local people. The emergence, risk, spread and control of diseases are affected by many complex bio-physical, environmental and socio-economic factors. These include climate and environmental change, land-use variation, changes in population and people’s behaviour. The evidence base for this scoping review comes from the work of a consortium, with the aim of integrating modelling approaches traditionally used in epidemiological, ecological and development research. A total of five examples of the impacts of participatory research on the choice of model structure are presented. Example 1 focused on using participatory research as a tool to structure a model. Example 2 looks at identifying the most relevant parameters of the system. Example 3 concentrates on identifying the most relevant regime of the system (e.g., temporal stability or otherwise), Example 4 examines the feedbacks from mathematical models to guide participatory research and Example 5 goes beyond the so-far described two-way interplay between participatory and mathematical approaches to look at the integration of multiple methods and frameworks. This scoping review describes examples of best practice in the use of participatory methods, illustrating their potential to overcome disciplinary hurdles and promote multidisciplinary collaboration, with the aim of making models and their predictions more useful for decision-making and policy formulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0110-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Grant, Catherine', 'Lo Iacono, Giovanni', 'Dzingirai, Vupenyu', 'Bett, Bernard', 'Winnebah, Thomas R. A.', 'Atkinson, Peter M.']",Infect Dis Poverty,,,False
9cda7cc79c0dee43d486d8165181e5b5ca09a817,PMC,Moving interdisciplinary science forward: integrating participatory modelling with mathematical modelling of zoonotic disease in Africa,http://dx.doi.org/10.1186/s40249-016-0110-4,PMC4766706,26916067,CC BY,"This review outlines the benefits of using multiple approaches to improve model design and facilitate multidisciplinary research into infectious diseases, as well as showing and proposing practical examples of effective integration. It looks particularly at the benefits of using participatory research in conjunction with traditional modelling methods to potentially improve disease research, control and management. Integrated approaches can lead to more realistic mathematical models which in turn can assist with making policy decisions that reduce disease and benefit local people. The emergence, risk, spread and control of diseases are affected by many complex bio-physical, environmental and socio-economic factors. These include climate and environmental change, land-use variation, changes in population and people’s behaviour. The evidence base for this scoping review comes from the work of a consortium, with the aim of integrating modelling approaches traditionally used in epidemiological, ecological and development research. A total of five examples of the impacts of participatory research on the choice of model structure are presented. Example 1 focused on using participatory research as a tool to structure a model. Example 2 looks at identifying the most relevant parameters of the system. Example 3 concentrates on identifying the most relevant regime of the system (e.g., temporal stability or otherwise), Example 4 examines the feedbacks from mathematical models to guide participatory research and Example 5 goes beyond the so-far described two-way interplay between participatory and mathematical approaches to look at the integration of multiple methods and frameworks. This scoping review describes examples of best practice in the use of participatory methods, illustrating their potential to overcome disciplinary hurdles and promote multidisciplinary collaboration, with the aim of making models and their predictions more useful for decision-making and policy formulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0110-4) contains supplementary material, which is available to authorized users.",2016 Feb 25,"['Grant, Catherine', 'Lo Iacono, Giovanni', 'Dzingirai, Vupenyu', 'Bett, Bernard', 'Winnebah, Thomas R. A.', 'Atkinson, Peter M.']",Infect Dis Poverty,,,True
f44786ccd9fbd63530866db7c60cac06fb9b0fb9,PMC,Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development,http://dx.doi.org/10.1038/srep21662,PMC4768256,26916998,CC BY,"Nucleoprotein (NP) is the most abundant type of RNA-binding viral protein in influenza A virus–infected cells and is necessary for viral RNA transcription and replication. Recent studies demonstrated that influenza NP is a valid target for antiviral drug development. The surface of the groove, covered with numerous conserved residues between the head and body domains of influenza A NP, plays a crucial role in RNA binding. To explore the mechanism by which NP binds RNA, we performed a series of site-directed mutagenesis in the RNA-binding groove, followed by surface plasmon resonance (SPR), to characterize the interactions between RNA and NP. Furthermore, a role of Y148 in NP stability and NP-RNA binding was evaluated. The aromatic residue of Y148 was found to stack with a nucleotide base. By interrupting the stacking interaction between Y148 and an RNA base, we identified an influenza virus NP inhibitor, (E, E)-1,7-bis(4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione; this inhibitor reduced the NP’s RNA-binding affinity and hindered viral replication. Our findings will be useful for the development of new drugs that disrupt the interaction between RNA and viral NP in the influenza virus.",2016 Feb 26,"['Liu, Chia-Lin', 'Hung, Hui-Chen', 'Lo, Shou-Chen', 'Chiang, Ching-Hui', 'Chen, I-Jung', 'Hsu, John T.-A.', 'Hou, Ming-Hon']",Sci Rep,,,True
a5bedf3a8d33e6b501c2203982eaaa5567011d86,PMC,Classical Swine Fever Virus vs. Classical Swine Fever Virus: The Superinfection Exclusion Phenomenon in Experimentally Infected Wild Boar,http://dx.doi.org/10.1371/journal.pone.0149469,PMC4768946,26919741,CC BY,"Two groups with three wild boars each were used: Group A (animals 1 to 3) served as the control, and Group B (animals 4 to 6) was postnatally persistently infected with the Cat01 strain of CSFV (primary virus). The animals, six weeks old and clinically healthy, were inoculated with the virulent strain Margarita (secondary virus). For exclusive detection of the Margarita strain, a specific qRT-PCR assay was designed, which proved not to have cross-reactivity with the Cat01 strain. The wild boars persistently infected with CSFV were protected from superinfection by the virulent CSFV Margarita strain, as evidenced by the absence of clinical signs and the absence of Margarita RNA detection in serum, swabs and tissue samples. Additionally, in PBMCs, a well-known target for CSFV viral replication, only the primary infecting virus RNA (Cat01 strain) could be detected, even after the isolation in ST cells, demonstrating SIE at the tissue level in vivo. Furthermore, the data analysis of the Margarita qRT-PCR, by means of calculated ΔCt values, supported that PBMCs from persistently infected animals were substantially protected from superinfection after in vitro inoculation with the Margarita virus strain, while this virus was able to infect naive PBMCs efficiently. In parallel, IFN-α values were undetectable in the sera from animals in Group B after inoculation with the CSFV Margarita strain. Furthermore, these animals were unable to elicit adaptive humoral (no E2-specific or neutralising antibodies) or cellular immune responses (in terms of IFN-γ-producing cells) after inoculation with the second virus. Finally, a sequence analysis could not detect CSFV Margarita RNA in the samples tested from Group B. Our results suggested that the SIE phenomenon might be involved in the evolution and phylogeny of the virus, as well as in CSFV control by vaccination. To the best of our knowledge, this study was one of the first showing efficient suppression of superinfection in animals, especially in the absence of IFN-α, which might be associated with the lack of innate immune mechanisms.",2016 Feb 26,"['Muñoz-González, Sara', 'Pérez-Simó, Marta', 'Colom-Cadena, Andreu', 'Cabezón, Oscar', 'Bohórquez, José Alejandro', 'Rosell, Rosa', 'Pérez, Lester Josué', 'Marco, Ignasi', 'Lavín, Santiago', 'Domingo, Mariano', 'Ganges, Llilianne']",PLoS One,,,True
31fa7844fdceee15b185eb734a7e1a09527431e2,PMC,High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling,http://dx.doi.org/10.1371/journal.ppat.1005473,PMC4769073,26919232,CC BY,"Members of the family Coronaviridae have the largest genomes of all RNA viruses, typically in the region of 30 kilobases. Several coronaviruses, such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV), are of medical importance, with high mortality rates and, in the case of SARS-CoV, significant pandemic potential. Other coronaviruses, such as Porcine epidemic diarrhea virus and Avian coronavirus, are important livestock pathogens. Ribosome profiling is a technique which exploits the capacity of the translating ribosome to protect around 30 nucleotides of mRNA from ribonuclease digestion. Ribosome-protected mRNA fragments are purified, subjected to deep sequencing and mapped back to the transcriptome to give a global “snap-shot” of translation. Parallel RNA sequencing allows normalization by transcript abundance. Here we apply ribosome profiling to cells infected with Murine coronavirus, mouse hepatitis virus, strain A59 (MHV-A59), a model coronavirus in the same genus as SARS-CoV and MERS-CoV. The data obtained allowed us to study the kinetics of virus transcription and translation with exquisite precision. We studied the timecourse of positive and negative-sense genomic and subgenomic viral RNA production and the relative translation efficiencies of the different virus ORFs. Virus mRNAs were not found to be translated more efficiently than host mRNAs; rather, virus translation dominates host translation at later time points due to high levels of virus transcripts. Triplet phasing of the profiling data allowed precise determination of translated reading frames and revealed several translated short open reading frames upstream of, or embedded within, known virus protein-coding regions. Ribosome pause sites were identified in the virus replicase polyprotein pp1a ORF and investigated experimentally. Contrary to expectations, ribosomes were not found to pause at the ribosomal frameshift site. To our knowledge this is the first application of ribosome profiling to an RNA virus.",2016 Feb 26,"['Irigoyen, Nerea', 'Firth, Andrew E.', 'Jones, Joshua D.', 'Chung, Betty Y.-W.', 'Siddell, Stuart G.', 'Brierley, Ian']",PLoS Pathog,,,True
b38901ead62c88fd24f7d28ca738711e13fb79ad,PMC,Mathematical modeling of the West Africa Ebola epidemic,http://dx.doi.org/10.7554/eLife.09186,PMC4769159,26646185,CC BY,"As of November 2015, the Ebola virus disease (EVD) epidemic that began in West Africa in late 2013 is waning. The human toll includes more than 28,000 EVD cases and 11,000 deaths in Guinea, Liberia, and Sierra Leone, the most heavily-affected countries. We reviewed 66 mathematical modeling studies of the EVD epidemic published in the peer-reviewed literature to assess the key uncertainties models addressed, data used for modeling, public sharing of data and results, and model performance. Based on the review, we suggest steps to improve the use of modeling in future public health emergencies. DOI: http://dx.doi.org/10.7554/eLife.09186.001",,"['Chretien, Jean-Paul', 'Riley, Steven', 'George, Dylan B']",eLife.; 4:e09186,,,True
af2e81683f4a37a0ada4acd6fbc495550306c86f,PMC,"Association between social support and recovery from post-traumatic stress disorder after flood: a 13–14 year follow-up study in Hunan, China",http://dx.doi.org/10.1186/s12889-016-2871-x,PMC4770534,26924178,CC BY,"BACKGROUND: Post-traumatic stress disorder (PTSD) is one of the most prevalent long-term psychiatric disorders among survivors of traumatic events. It is well established that social support has been related to the onset of PTSD after natural disasters. However, very little is known whether or not social support has had an influence on the recovery from the PTSD that was diagnosed after floods. This study, therefore, made a follow-up assessment of PTSD in flood victims 13–14 years after they were diagnosed with PTSD in 2000 to measure the prevalence rate of PTSD among them and identify the association between social support and their recovery from PTSD. METHODS: Victims who had experienced Dongting Lake flood in 1998 and had been diagnosed as having PTSD in 2000 were enrolled in this study. A follow-up survey was done between the years 2013 and 2014 to diagnose the victims again of PTSD using the DSM-IV criteria. Social support and its three dimensions were measured using the Chinese version of Social Support Rating Scale (SSRS), including objective support, subjective support and support utilization. Data were collected through face-to-face interviews using a structured questionnaire. Bivariate and multivariate logistic regression analyses were used to examine the relationship between social support and the recovery from PTSD after flood. RESULTS: Out of 321 subjects with prior PTSD, 51 (15.89 %) were diagnosed as still having PTSD. Logistic regression analyses indicated that the recovery from prior PTSD was significantly associated with social support (odds ratio (OR) =0.202, 95 % confidence interval (95 % CI): 0.047–0.878), subjective support (OR = 0.236, 95 % CI: 0.080–0.694) and support utilization (OR = 0.245, 95 % CI: 0.071–0.844). CONCLUSIONS: The prevalence rate of current PTSD indicates that natural disasters, such as floods, may affect the mental health of victims for a long time. Social support was significantly associated with the recovery from prior PTSD, especially subjective support and support utilization.",2016 Feb 29,"['Dai, Wenjie', 'Chen, Long', 'Tan, Hongzhuan', 'Wang, Jieru', 'Lai, Zhiwei', 'Kaminga, Atipatsa C.', 'Li, Yan', 'Liu, Aizhong']",BMC Public Health,,,True
dd48e5c738239c1d9b0497cbf4b5219bf252c0b8,PMC,Modelling input-output flows of severe acute respiratory syndrome in mainland China,http://dx.doi.org/10.1186/s12889-016-2867-6,PMC4770707,26924026,CC BY,"BACKGROUND: Severe acute respiratory syndrome (SARS) originated in China in 2002, and it spread to 26 provinces in mainland China and 32 countries across five continents in a matter of months. This outbreak resulted in 774 deaths. However, the spatial features and potential determinants of SARS input-output flows remain unclear. METHODS: We used an adjusted spatial interaction model to examine the spatial effects and potential factors associated with SARS input-output flows. RESULTS: The presence of origin-based spatial dependence positively affected SARS input-output flows from the neighbours of the origin regions. Two components of the input-output flows, migrant and hospitalization flows, exhibited distinctive features. The origin-based and destination-based spatial dependence positively affected migrant flows (i.e., due to those seeking jobs) from the neighbours of origin and destination locations. Similarly, the destination-based spatial dependence also positively affected hospitalization flows (i.e., due to those seeking treatment) from the neighbours of destination regions. However, the origin-to-destination based spatial dependence negatively affected hospitalisation flows from the neighbours of origin-to-destination regions. The direct effects accounted for 78 % of the SARS input-output flows, which was 3.56-fold greater than the indirect effects. Differences in regional income drove the SARS input-output flows. Therefore, urban income had a positive effect, whereas rural income had a negative effect. Total interregional flows increased by 3.54 % with a 1 % increase in urban income, and intraregional flows increased by 8.35 %. In contrast, the total interregional flows decreased by 3.38 % with a 1 % increase in rural income, and intraregional flows declined by 2.29 %. Railway capacity, per person gross domestic product (PGDP), urban rate and the law of distance decay also affected the input-output flows. CONCLUSIONS: Our results confirm that the SARS input-output flows presented significant geographic spatial heterogeneity and spatial effects. Income differences were the major cause of the flows between pairs of regions. Railway capacity, PGDP, and urban rate also played important roles. These findings provide valuable information for the Chinese government to control the future spread of nationwide epidemics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-2867-6) contains supplementary material, which is available to authorized users.",2016 Feb 29,"['Wang, Li', 'Wang, Jinfeng', 'Xu, Chengdong', 'Liu, Tiejun']",BMC Public Health,,,True
d0146d4c8a05561b617e944b7f7c523c46612dc8,PMC,Myricetin: A Dietary Molecule with Diverse Biological Activities,http://dx.doi.org/10.3390/nu8020090,PMC4772053,26891321,CC BY,"Myricetin is a common plant-derived flavonoid and is well recognised for its nutraceuticals value. It is one of the key ingredients of various foods and beverages. The compound exhibits a wide range of activities that include strong anti-oxidant, anticancer, antidiabetic and anti-inflammatory activities. It displays several activities that are related to the central nervous system and numerous studies have suggested that the compound may be beneficial to protect against diseases such as Parkinson’s and Alzheimer’s. The use of myricetin as a preserving agent to extend the shelf life of foods containing oils and fats is attributed to the compound’s ability to protect lipids against oxidation. A detailed search of existing literature revealed that there is currently no comprehensive review available on this important molecule. Hence, the present work includes the history, synthesis, pharmaceutical applications and toxicity studies of myricetin. This report also highlights structure-activity relationships and mechanisms of action for various biological activities.",2016 Feb 16,"['Semwal, Deepak Kumar', 'Semwal, Ruchi Badoni', 'Combrinck, Sandra', 'Viljoen, Alvaro']",Nutrients,,,True
343aeda9b3a81a9db2f40386f3991ef6c48338ce,PMC,How Inhomogeneous Site Percolation Works on Bethe Lattices: Theory and Application,http://dx.doi.org/10.1038/srep22420,PMC4772486,26926785,CC BY,"Inhomogeneous percolation, for its closer relationship with real-life, can be more useful and reasonable than homogeneous percolation to illustrate the critical phenomena and dynamical behaviour of complex networks. However, due to its intricacy, the theoretical framework of inhomogeneous percolation is far from being complete and many challenging problems are still open. In this paper, we first investigate inhomogeneous site percolation on Bethe Lattices with two occupation probabilities, and then extend the result to percolation with m occupation probabilities. The critical behaviour of this inhomogeneous percolation is shown clearly by formulating the percolation probability [Image: see text] with given occupation probability p, the critical occupation probability [Image: see text], and the average cluster size [Image: see text] where p is subject to [Image: see text]. Moreover, using the above theory, we discuss in detail the diffusion behaviour of an infectious disease (SARS) and present specific disease-control strategies in consideration of groups with different infection probabilities.",2016 Mar 1,"['Ren, Jingli', 'Zhang, Liying', 'Siegmund, Stefan']",Sci Rep,,,True
a7655a74468e485dfd7f45390c5be4c4aa9361a8,PMC,Comparative Epidemiology of Human Infections with Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome Coronaviruses among Healthcare Personnel,http://dx.doi.org/10.1371/journal.pone.0149988,PMC4773072,26930074,CC BY,"The largest nosocomial outbreak of Middle East respiratory syndrome (MERS) occurred in South Korea in 2015. Health Care Personnel (HCP) are at high risk of acquiring MERS-Coronavirus (MERS-CoV) infections, similar to the severe acute respiratory syndrome (SARS)-Coronavirus (SARS-CoV) infections first identified in 2003. This study described the similarities and differences in epidemiological and clinical characteristics of 183 confirmed global MERS cases and 98 SARS cases in Taiwan associated with HCP. The epidemiological findings showed that the mean age of MERS-HCP and total MERS cases were 40 (24~74) and 49 (2~90) years, respectively, much older than those in SARS [SARS-HCP: 35 (21~68) years, p = 0.006; total SARS: 42 (0~94) years, p = 0.0002]. The case fatality rates (CFR) was much lower in MERS-HCP [7.03% (9/128)] or SARS-HCP [12.24% (12/98)] than the MERS-non-HCP [36.96% (34/92), p<0.001] or SARS-non-HCP [24.50% (61/249), p<0.001], however, no difference was found between MERS-HCP and SARS-HCP [p = 0.181]. In terms of clinical period, the days from onset to death [13 (4~17) vs 14.5 (0~52), p = 0.045] and to discharge [11 (5~24) vs 24 (0~74), p = 0.010] and be hospitalized days [9.5 (3~22) vs 22 (0~69), p = 0.040] were much shorter in MERS-HCP than SARS-HCP. Similarly, days from onset to confirmation were shorter in MERS-HCP than MERS-non-HCP [6 (1~14) vs 10 (1~21), p = 0.044]. In conclusion, the severity of MERS-HCP and SARS-HCP was lower than that of MERS-non-HCP and SARS-non-HCP due to younger age and early confirmation in HCP groups. However, no statistical difference was found in MERS-HCP and SARS-HCP. Thus, prevention of nosocomial infections involving both novel Coronavirus is crucially important to protect HCP.",2016 Mar 1,"['Liu, Shelan', 'Chan, Ta-Chien', 'Chu, Yu-Tseng', 'Wu, Joseph Tsung-Shu', 'Geng, Xingyi', 'Zhao, Na', 'Cheng, Wei', 'Chen, Enfu', 'King, Chwan-Chuen']",PLoS One,,,True
6620e8406c8ad908234205ff102d7bd2cc0dce72,PMC,Characterization and Vaccine Potential of Outer Membrane Vesicles Produced by Haemophilus parasuis,http://dx.doi.org/10.1371/journal.pone.0149132,PMC4773134,26930282,CC0,"Haemophilus parasuis is a Gram-negative bacterium that colonizes the upper respiratory tract of swine and is capable of causing a systemic infection, resulting in high morbidity and mortality. H. parasuis isolates display a wide range of virulence and virulence factors are largely unknown. Commercial bacterins are often used to vaccinate swine against H. parasuis, though strain variability and lack of cross-reactivity can make this an ineffective means of protection. Outer membrane vesicles (OMV) are spherical structures naturally released from the membrane of bacteria and OMV are often enriched in toxins, signaling molecules and other bacterial components. Examination of OMV structures has led to identification of virulence factors in a number of bacteria and they have been successfully used as subunit vaccines. We have isolated OMV from both virulent and avirulent strains of H. parasuis, have examined their protein content and assessed their ability to induce an immune response in the host. Vaccination with purified OMV derived from the virulent H. parasuis Nagasaki strain provided protection against challenge with a lethal dose of the bacteria.",2016 Mar 1,"['McCaig, William D.', 'Loving, Crystal L.', 'Hughes, Holly R.', 'Brockmeier, Susan L.']",PLoS One,,,True
ef39c95cda9c94452dc64147ea7d9c825e03b8bb,PMC,"Perception, Price and Preference: Consumption and Protection of Wild Animals Used in Traditional Medicine",http://dx.doi.org/10.1371/journal.pone.0145901,PMC4773180,26930487,CC BY,"A wide array of wildlife species, including many animals, are used in traditional medicines across many medicinal systems, including in Traditional Chinese Medicine (TCM). Due to over-exploitation and habitat loss, the populations of many animals commonly used in TCM have declined and are unable to meet market demand. A number of measures have been taken to try to reduce the impact that this large and growing market for TCM may have on wild animal species. Consumer preferences and behavior are known to play an important role in the consumption and protection of wild animals used in traditional medicine, and thus are likely to be an important factor in the success of many of these mechanisms—particularly given the significant percentage of TCMs that are over-the-counter products (access to which is not mediated by practitioners). In this study we conducted questionnaires and designed stated preference experiments embodying different simulation scenarios using a random sample of the population in Beijing to elicit individuals’ knowledge, perceptions and preferences toward wild or farmed animal materials and their substitutes used in traditional Chinese medicine. We found that respondents had a stated preference for wild materials over farm-raised and other alternatives because they believe that the effectiveness of wild-sourced materials is more credible than that of other sources. However, we also found that, although respondents used TCM products, they had a poor understanding of the function or composition of either traditional Chinese medicines or proprietary Chinese medicines (PCM), and paid little attention to the composition of products when making purchasing decisions. Furthermore, awareness of the need for species protection, or “conservation consciousness” was found to play an important role in willingness to accept substitutions for wild animal materials, while traditional animal medicinal materials (TAMs) derived from well-known endangered species, such as bear bile and tiger bone, show relatively higher substitutability. These results suggest that there is still hope for conservation measures which seek to promote a transition to farmed animal, plant and synthetic ingredients and provide clear directions for future social marketing, education and engagement efforts.",2016 Mar 1,"['Liu, Zhao', 'Jiang, Zhigang', 'Fang, Hongxia', 'Li, Chunwang', 'Mi, Aizi', 'Chen, Jing', 'Zhang, Xiaowei', 'Cui, Shaopeng', 'Chen, Daiqiang', 'Ping, Xiaoge', 'Li, Feng', 'Li, Chunlin', 'Tang, Songhua', 'Luo, Zhenhua', 'Zeng, Yan', 'Meng, Zhibin']",PLoS One,,,True
5ef330551dd1c93b532c49305501f9a5abd3d799,PMC,T Cell Response in Patients with Implanted Biological and Mechanical Prosthetic Heart Valves,http://dx.doi.org/10.1155/2016/1937564,PMC4773556,26989331,CC BY,"The study was aimed at assessing T cell subsets of peripheral blood from recipients of long-term functioning (more than 60 months) biological and mechanical heart valve prostheses. The absolute and relative number of CD4 and CD8 T cell subsets was analyzed: naïve (N, CD45RA(+)CD62L(+)), central memory (CM, CD45RA(−)CD62L(+)), effector memory (EM, CD45RA(−)CD62L(−)), and terminally differentiated CD45RA-positive effector memory (TEMRA, CD45RA(+)CD62L(−)) in 25 persons with biological and 7 with mechanical prosthesis compared with 48 apparently healthy volunteers. The relative and absolute number of central memory and naïve CD3(+)CD8(+) in patients with biological prosthesis was decreased (p < 0.001). Meanwhile the number of CD45RA(+)CD62L(−)CD3(+)CD8(+) and CD3(+)CD4(+) was increased (p < 0.001). Patients with mechanical prosthesis had increased absolute and relative number of CD45RA(+)CD62L(−)CD3(+)CD8(+) cells (p = 0.006). Also the relative number of CD3(+)CD4(+) cells was reduced (p = 0.04). We assume that altered composition of T cell subsets points at development of xenograft rejection reaction against both mechanical and biological heart valve prostheses.",2016 Feb 17,"['Barbarash, L.', 'Kudryavtsev, I.', 'Rutkovskaya, N.', 'Golovkin, A.']",Mediators Inflamm,,,True
681a28c40a3da8f03c0f86a91db26bc8416967ed,PMC,The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes,http://dx.doi.org/10.1186/s12864-016-2500-1,PMC4774177,26931144,CC BY,"BACKGROUND: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. RESULTS: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is “Centromere - Class II – Class III – Class I”. DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. CONCLUSIONS: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2500-1) contains supplementary material, which is available to authorized users.",2016 Mar 1,"['Plasil, Martin', 'Mohandesan, Elmira', 'Fitak, Robert R.', 'Musilova, Petra', 'Kubickova, Svatava', 'Burger, Pamela A.', 'Horin, Petr']",BMC Genomics,,,False
34829c7a24387bede0b75ec97fdd37e1a5ae6c4e,PMC,The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes,http://dx.doi.org/10.1186/s12864-016-2500-1,PMC4774177,26931144,CC BY,"BACKGROUND: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. RESULTS: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is “Centromere - Class II – Class III – Class I”. DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. CONCLUSIONS: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2500-1) contains supplementary material, which is available to authorized users.",2016 Mar 1,"['Plasil, Martin', 'Mohandesan, Elmira', 'Fitak, Robert R.', 'Musilova, Petra', 'Kubickova, Svatava', 'Burger, Pamela A.', 'Horin, Petr']",BMC Genomics,,,False
824044d0d0f1262cd632945cc54889335133a9bb,PMC,The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes,http://dx.doi.org/10.1186/s12864-016-2500-1,PMC4774177,26931144,CC BY,"BACKGROUND: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. RESULTS: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is “Centromere - Class II – Class III – Class I”. DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. CONCLUSIONS: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2500-1) contains supplementary material, which is available to authorized users.",2016 Mar 1,"['Plasil, Martin', 'Mohandesan, Elmira', 'Fitak, Robert R.', 'Musilova, Petra', 'Kubickova, Svatava', 'Burger, Pamela A.', 'Horin, Petr']",BMC Genomics,,,False
9cf367c15e9c4bbfea103bbb629fba2b48a20afc,PMC,The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes,http://dx.doi.org/10.1186/s12864-016-2500-1,PMC4774177,26931144,CC BY,"BACKGROUND: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. RESULTS: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is “Centromere - Class II – Class III – Class I”. DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. CONCLUSIONS: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2500-1) contains supplementary material, which is available to authorized users.",2016 Mar 1,"['Plasil, Martin', 'Mohandesan, Elmira', 'Fitak, Robert R.', 'Musilova, Petra', 'Kubickova, Svatava', 'Burger, Pamela A.', 'Horin, Petr']",BMC Genomics,,,False
cb7cb23bf68e88cbd3334bb46eb899d7a873d115,PMC,The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes,http://dx.doi.org/10.1186/s12864-016-2500-1,PMC4774177,26931144,CC BY,"BACKGROUND: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. RESULTS: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is “Centromere - Class II – Class III – Class I”. DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. CONCLUSIONS: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2500-1) contains supplementary material, which is available to authorized users.",2016 Mar 1,"['Plasil, Martin', 'Mohandesan, Elmira', 'Fitak, Robert R.', 'Musilova, Petra', 'Kubickova, Svatava', 'Burger, Pamela A.', 'Horin, Petr']",BMC Genomics,,,False
15dd9abbe4084c12712f094415c5ca9980aaacda,PMC,The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes,http://dx.doi.org/10.1186/s12864-016-2500-1,PMC4774177,26931144,CC BY,"BACKGROUND: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. RESULTS: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is “Centromere - Class II – Class III – Class I”. DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. CONCLUSIONS: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2500-1) contains supplementary material, which is available to authorized users.",2016 Mar 1,"['Plasil, Martin', 'Mohandesan, Elmira', 'Fitak, Robert R.', 'Musilova, Petra', 'Kubickova, Svatava', 'Burger, Pamela A.', 'Horin, Petr']",BMC Genomics,,,True
a127919cf960d1c72c3e29ce2ec08c67d6aba59f,PMC,"Construction and characterization of recombinant human adenovirus type 5 expressing foot-and-mouth disease virus capsid proteins of Indian vaccine strain, O/IND/R2/75",http://dx.doi.org/10.14202/vetworld.2015.147-155,PMC4774695,27047064,CC BY,"AIM: Generation of recombinant human adenovirus type 5 expressing foot-and-mouth disease virus (FMDV) capsid protein genes along with full-length 2B, 3B and 3C(pro) and its characterization. MATERIALS AND METHODS: FMD viral RNA isolation, cDNA synthesis, and polymerase chain reaction were performed to synthesize expression cassettes (P1-2AB3BC(wt) and P1-2AB3BC(m)) followed by cloning in pShuttle-CMV vector. Chemically competent BJ5183-AD-1 cells were transformed with the recombinant pShuttle-CMV to produce recombinant adenoviral plasmids. HEK-293 cells were transfected with the recombinant adenoviral plasmids to generate recombinant adenoviruses (hAd5/P1-2AB3BC(wt) and hAd5/P1-2AB3BC(m)). Expression of the target proteins was analyzed by sandwich ELISA and indirect immunofluorescence assay. The recombinant adenoviruses were purified and concentrated by CsCl density gradient ultracentrifugation. Growth kinetics and thermostability of the recombinant adenoviruses were compared with that of non-recombinant replication-defective adenovirus (dAd5). RESULTS: The recombinant adenoviruses containing capsid protein genes of the FMDV O/IND/R2/75 were generated and amplified in HEK-293 cells. The titer of the recombinant adenoviruses was approximately 10(8), 10(9.5) and 10(11) TCID(50)/ml in supernatant media, cell lysate and CsCl purified preparation, respectively. Expression of the FMDV capsid protein was detectable in sandwich ELISA and confirmed by immunofluorescence assay. Growth kinetics of the recombinant adenoviruses did not reveal a significant difference when compared with that of dAd5. A decrement of up to 10-fold at 4°C and 21-fold at 37°C was recorded in the virus titers during 60 h incubation period and found to be statistically significant (p<0.01). CONCLUSION: Recombinant adenoviruses expressing capsid proteins of the FMDV O/IND/R2/75 were constructed and produced in high titers. In vitro expression of the target proteins in the adenovirus vector system was detected by sandwich ELISA and immunofluorescence assay.",2015 Feb 10,"['Kumar, Ramesh', 'Sreenivasa, B. P.', 'Tamilselvan, R. P.']",Vet World,,,True
b6b06d62a3af9c36824d3c674f4d43d6d78d9073,PMC,Validation of γ-radiation and ultraviolet as a new inactivators for foot and mouth disease virus in comparison with the traditional methods,http://dx.doi.org/10.14202/vetworld.2015.1088-1098,PMC4774778,27047204,CC BY,"AIM: The present work deals with different methods for foot and mouth disease virus (FMDV) inactivation for serotypes O/pan Asia, A/Iran05, and SAT-2/2012 by heat, gamma radiation, and ultraviolet (UV) in comparison with the traditional methods and their effects on the antigenicity of viruses for production of inactivated vaccines. MATERIALS AND METHODS: FMDV types O/pan Asia, A/Iran05, and SAT-2/2012 were propagated in baby hamster kidney 21 (BHK21) and titrated then divided into five parts; the first part inactivated with heat, the second part inactivated with gamma radiation, the third part inactivated with UV light, the fourth part inactivated with binary ethylamine, and the last part inactivated with combination of binary ethylamine and formaldehyde (BEI+FA). Evaluate the method of inactivation via inoculation in BHK21, inoculation in suckling baby mice and complement fixation test then formulate vaccine using different methods of inactivation then applying the quality control tests to evaluate each formulated vaccine. RESULTS: The effect of heat, gamma radiation, and UV on the ability of replication of FMDV “O/pan Asia, A/Iran05, and SAT-2/2012” was determined through BHK cell line passage. Each of the 9 virus aliquots titer 10(8) TCID(50) (3 for each strain) were exposed to 37, 57, and 77°C for 15, 30, and 45 min. Similarly, another 15 aliquots (5 for each strain) contain 1 mm depth of the exposed samples in petri-dish was exposed to UV light (252.7 nm wavelength: One foot distance) for 15, 30, 45, 60, and 65 min. Different doses of gamma radiation (10, 20, 25, 30, 35, 40, 45, 50, 55, and 60 KGy) were applied in a dose rate 0.551 Gy/s for each strain and repeated 6 times for each dose. FMDV (O/pan Asia, A/Iran05, and SAT-2/2012) were inactivated when exposed to heat ≥57°C for 15 min. The UV inactivation of FMDV (O/pan Asia and SAT-2) was obtained within 60 min and 65 min for type A/Iran05. The ideal dose for inactivation of FMDV (O/pan Asia, A/Iran05, and SAT-2/2012) with gamma radiation were 55-60 and 45 kGy, respectively. Inactivation of FMDV with binary was 20, 24 and 16 hr for O/pan Asia, A/Iran05, and SAT-2/2012, respectively while inactivation by (BEI+FA) was determined after 18, 19 and 11 hr for O/pan-Asia, A/Iran 05, and SAT-2/2012, respectively. The antigenicity of control virus before inactivation was 1/32, it was not changed after inactivation in case of gamma radiation and (BEI+FA) and slightly decrease to 1/16 in case of binary and declined to 1/2, 1/4 in case of heat and UV inactivation, respectively. The immune response induced by inactivated FMD vaccines by gamma radiation and (BEI+FA) lasted to 9 months post-vaccination, while the binary only still up to 8 months post-vaccination but heat and UV-inactivated vaccines were not effective. CONCLUSION: Gamma radiation could be considered a good new inactivator inducing the same results of inactivated vaccine by binary with formaldehyde (BEI+FA).",2015 Sep 19,"['Mahdy, Safy El din', 'Hassanin, Amr Ismail', 'Gamal El-Din, Wael Mossad', 'Ibrahim, Ehab El-Sayed', 'Fakhry, Hiam Mohamed']",Vet World,,,True
9ce0da57763dfa3cebfb1463093ff0bba3333a25,PMC,"Prevalence of Cryptosporidia, Eimeria, Giardia, and Strongyloides in pre-weaned calves on smallholder dairy farms in Mukurwe-ini district, Kenya",http://dx.doi.org/10.14202/vetworld.2015.1118-1125,PMC4774781,27047207,CC BY,"AIM: Gastrointestinal diseases are among the leading causes of calf morbidity and mortality in Kenya and elsewhere. This study was undertaken to determine the prevalence of Cryptosporidia, Eimeria, Giardia, and Strongyloides in calves on smallholder dairy farms (SDF) in Mukurwe-ini District, Nyeri County, Kenya. These infections have been associated with economic losses by decreased growth rates, decreased productivity, and increased susceptibility to other diseases. MATERIALS AND METHODS: An observational study was conducted on 109 farms in Mukurwe-ini District, Nyeri County, Kenya, where 220 calf fecal samples (each calf at 4 and 6 weeks of age) from 110 calves (1 set of twins) were collected and analyzed for Cryptosporidia, Eimeria, Giardia, and helminth parasites. RESULTS: Eimeria oocysts, Cryptosporidia oocysts, and Strongyloides eggs were detected in the fecal samples examined, but no Giardia cysts were found. The overall period prevalence of Eimeria, Cryptosporidia, and Strongyloides was 42.7% (47/110), 13.6% (15/110), and 5.4% (6/110), respectively. The prevalence at 4 weeks of age for Eimeria, Cryptosporidia, and Strongyloides was 30.0% (33/110), 8.2% (9/110), and 3.7% (4/109), respectively, while the prevalence at 6 weeks of age was 20.2% (22/109), 6.5% (7/107), and 2.7% (3/110), respectively. There was, however, no significant difference in the prevalence at 4 and 6 weeks (p>0.05). CONCLUSION: Findings from this study show that Eimeria, Cryptosporidia, and Strongyloides, are prevalent in the study area and indicate the need to adopt optimal management practices to control infections in calves.",2015 Sep 22,"['Peter, Getrude Shepelo', 'Gitau, George Karuoya', 'Mulei, Charles Matiku', 'Vanleeuwen, John', 'Richards, Shauna', 'Wichtel, Jeff', 'Uehlinger, Fabienne', 'Mainga, Omwando']",Vet World,,,True
f880418303ca5f21c858eca97f076216919bb4b5,PMC,Defensins Potentiate a Neutralizing Antibody Response to Enteric Viral Infection,http://dx.doi.org/10.1371/journal.ppat.1005474,PMC4774934,26933888,CC BY,"α-defensins are abundant antimicrobial peptides with broad, potent antibacterial, antifungal, and antiviral activities in vitro. Although their contribution to host defense against bacteria in vivo has been demonstrated, comparable studies of their antiviral activity in vivo are lacking. Using a mouse model deficient in activated α-defensins in the small intestine, we show that Paneth cell α-defensins protect mice from oral infection by a pathogenic virus, mouse adenovirus 1 (MAdV-1). Survival differences between mouse genotypes are lost upon parenteral MAdV-1 infection, strongly implicating a role for intestinal defenses in attenuating pathogenesis. Although differences in α-defensin expression impact the composition of the ileal commensal bacterial population, depletion studies using broad-spectrum antibiotics revealed no effect of the microbiota on α-defensin-dependent viral pathogenesis. Moreover, despite the sensitivity of MAdV-1 infection to α-defensin neutralization in cell culture, we observed no barrier effect due to Paneth cell α-defensin activation on the kinetics and magnitude of MAdV-1 dissemination to the brain. Rather, a protective neutralizing antibody response was delayed in the absence of α-defensins. This effect was specific to oral viral infection, because antibody responses to parenteral or mucosal ovalbumin exposure were not affected by α-defensin deficiency. Thus, α-defensins play an important role as adjuvants in antiviral immunity in vivo that is distinct from their direct antiviral activity observed in cell culture.",2016 Mar 2,"['Gounder, Anshu P.', 'Myers, Nicolle D.', 'Treuting, Piper M.', 'Bromme, Beth A.', 'Wilson, Sarah S.', 'Wiens, Mayim E.', 'Lu, Wuyuan', 'Ouellette, André J.', 'Spindler, Katherine R.', 'Parks, William C.', 'Smith, Jason G.']",PLoS Pathog,,,True
d21eaa427bea34a60db8a4fec53ee3a5021a1eba,PMC,CpG Improves Influenza Vaccine Efficacy in Young Adult but Not Aged Mice,http://dx.doi.org/10.1371/journal.pone.0150425,PMC4774967,26934728,CC BY,"Several studies have shown a reduced efficacy of influenza vaccines in the elderly compared to young adults. In this study, we evaluated the immunogenicity and protective efficacy of a commercially available inactivated influenza vaccine (Fluzone(®)) in young adult and aged mice. C57/BL6 mice were administered a single or double immunization of Fluzone(®) with or without CpG and challenged intranasally with H1N1 A/California/09 virus. A double immunization of Fluzone(®) adjuvanted with CpG elicited the highest level of protection in young adult mice which was associated with increases in influenza specific IgG, elevated HAI titres, reduced viral titres and lung inflammation. In contrast, the vaccine schedule which provided fully protective immunity in young adult mice conferred limited protection in aged mice. Antigen presenting cells from aged mice were found to be less responsive to in vitro stimulation by Fluzone and CpG which may partially explain this result. Our data are supportive of studies that have shown limited effectiveness of influenza vaccines in the elderly and provide important information relevant to the design of more immunogenic vaccines in this age group.",2016 Mar 2,"['Ramirez, Alejandro', 'Co, Mary', 'Mathew, Anuja']",PLoS One,,,True
69060a231f9cae90c08c07b01d74da4f699cee8b,PMC,Modes of Antiviral Action of Chemical Portions and Constituents from Woad Root Extract against Influenza Virus A FM1,http://dx.doi.org/10.1155/2016/2537294,PMC4775799,26989425,CC BY,"Woad root has been used for the prevention of influenza for hundreds of years in many Asian countries. In this study, the antiviral modes of clemastanin B (CB), epigoitrin, phenylpropanoid portion (PEP), and the mixture of phenylpropanoids, alkaloids, and organic acid portions (PEP + ALK + OA) from wood root extract against influenza virus A FM1 were investigated. The results revealed that CB, epigoitrin, PEP, and PEP + ALK + OA exert their anti-influenza activity via inhibiting the virus multiplication, prophylaxis, and blocking the virus attachment. The primary mode of action of PEP and PEP + ALK + OA is the inhibition of virus replication. The inhibitory effect on virus attachment and multiplication is the main modes for epigoitrin. All the compounds or chemical portions from woad root extract tested in this study do not have direct virucidal activity. Our results provided the comprehensive analysis of the antiviral mechanism of wood root extract.",2016 Feb 18,"['Su, Jia-Hang', 'Diao, Rui-Gang', 'Lv, Shu-Guang', 'Mou, Xiao-Dong', 'Li, Kefeng']",Evid Based Complement Alternat Med,,,False
be738f9bf3b9a980ffecede2db4d06ea3f2518bd,PMC,Modes of Antiviral Action of Chemical Portions and Constituents from Woad Root Extract against Influenza Virus A FM1,http://dx.doi.org/10.1155/2016/2537294,PMC4775799,26989425,CC BY,"Woad root has been used for the prevention of influenza for hundreds of years in many Asian countries. In this study, the antiviral modes of clemastanin B (CB), epigoitrin, phenylpropanoid portion (PEP), and the mixture of phenylpropanoids, alkaloids, and organic acid portions (PEP + ALK + OA) from wood root extract against influenza virus A FM1 were investigated. The results revealed that CB, epigoitrin, PEP, and PEP + ALK + OA exert their anti-influenza activity via inhibiting the virus multiplication, prophylaxis, and blocking the virus attachment. The primary mode of action of PEP and PEP + ALK + OA is the inhibition of virus replication. The inhibitory effect on virus attachment and multiplication is the main modes for epigoitrin. All the compounds or chemical portions from woad root extract tested in this study do not have direct virucidal activity. Our results provided the comprehensive analysis of the antiviral mechanism of wood root extract.",2016 Feb 18,"['Su, Jia-Hang', 'Diao, Rui-Gang', 'Lv, Shu-Guang', 'Mou, Xiao-Dong', 'Li, Kefeng']",Evid Based Complement Alternat Med,,,True
64f5af205494b75764762ed86fd202387c77b0b7,PMC,"Spatial and Temporal Epidemiology of Lumpy Skin Disease in the Middle East, 2012–2015",http://dx.doi.org/10.3389/fvets.2016.00019,PMC4776163,26973845,CC BY,"Lumpy skin disease virus (LSDV) is an infectious disease of cattle that can have severe economic implications. New LSD outbreaks are currently circulating in the Middle East (ME). Since 2012, severe outbreaks were reported in cattle across the region. Characterizing the spatial and temporal dynamics of LSDV in cattle populations is prerequisite for guiding successful surveillance and control efforts at a regional level in the ME. Here, we aim to model the ecological niche of LSDV and identify epidemic progression patterns over the course of the epidemic. We analyzed publically available outbreak data from the ME for the period 2012–2015 using presence-only maximum entropy ecological niche modeling and the time-dependent method for the estimation of the effective reproductive number (R-TD). High-risk areas (probability >0.60) for LSDV identified by ecological niche modeling included parts of many northeastern ME countries, though Israel and Turkey were estimated to be the most suitable locations for occurrence of LSDV outbreaks. The most important environmental predictors that contributed to the ecological niche of LSDV included annual precipitation, land cover, mean diurnal range, type of livestock production system, and global livestock densities. Average monthly effective R-TD was equal to 2.2 (95% CI: 1.2, 3.5), whereas the largest R-TD was estimated in Israel (R-TD = 22.2, 95 CI: 15.2, 31.5) in September 2013, which indicated that the demographic and environmental conditions during this period were suitable to LSDV super-spreading events. The sharp drop of Isreal’s inferred R-TD in the following month reflected the success of their 2013 vaccination campaign in controlling the disease. Our results identified areas in which underreporting of LSDV outbreaks may have occurred. More epidemiological information related to cattle populations are needed to further improve the inferred spatial and temporal characteristics of currently circulating LSDV. However, the methodology presented here may be useful in guiding the design of risk-based surveillance and control programs in the region as well as aid in the formulation of epidemic preparedness plans in neighboring LSDV-free countries.",2016 Mar 3,"['Alkhamis, Mohammad A.', 'VanderWaal, Kimberly']",Front Vet Sci,,,True
1adab26eb1167a39014dc503174f7d34f9087664,PMC,Pandemic Influenza A (H1N1) Virus Infection Increases Apoptosis and HIV-1 Replication in HIV-1 Infected Jurkat Cells,http://dx.doi.org/10.3390/v8020033,PMC4776188,26848681,CC BY,"Influenza virus infection has a significant impact on public health, since it is a major cause of morbidity and mortality. It is not well-known whether influenza virus infection affects cell death and human immunodeficiency virus (HIV)-1 replication in HIV-1-infected patients. Using a lymphoma cell line, Jurkat, we examined the in vitro effects of pandemic influenza A (H1N1) virus (pH1N1) infection on cell death and HIV-1 RNA production in infected cells. We found that pH1N1 infection increased apoptotic cell death through Fas and Bax-mediated pathways in HIV-1-infected Jurkat cells. Infection with pH1N1 virus could promote HIV-1 RNA production by activating host transcription factors including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), nuclear factor of activated T-cells (NFAT) and activator protein 1 (AP-1) through mitogen-activated protein kinases (MAPK) pathways and T-cell antigen receptor (TCR)-related pathways. The replication of HIV-1 latent infection could be reactivated by pH1N1 infection through TCR and apoptotic pathways. These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways.",2016 Feb 2,"['Wang, Xue', 'Tan, Jiying', 'Biswas, Santanu', 'Zhao, Jiangqin', 'Devadas, Krishnakumar', 'Ye, Zhiping', 'Hewlett, Indira']",Viruses,,,True
0d6a45540d196e47056de4ba18b8b5b3429d3407,PMC,Pandemic Influenza A (H1N1) Virus Infection Increases Apoptosis and HIV-1 Replication in HIV-1 Infected Jurkat Cells,http://dx.doi.org/10.3390/v8020033,PMC4776188,26848681,CC BY,"Influenza virus infection has a significant impact on public health, since it is a major cause of morbidity and mortality. It is not well-known whether influenza virus infection affects cell death and human immunodeficiency virus (HIV)-1 replication in HIV-1-infected patients. Using a lymphoma cell line, Jurkat, we examined the in vitro effects of pandemic influenza A (H1N1) virus (pH1N1) infection on cell death and HIV-1 RNA production in infected cells. We found that pH1N1 infection increased apoptotic cell death through Fas and Bax-mediated pathways in HIV-1-infected Jurkat cells. Infection with pH1N1 virus could promote HIV-1 RNA production by activating host transcription factors including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), nuclear factor of activated T-cells (NFAT) and activator protein 1 (AP-1) through mitogen-activated protein kinases (MAPK) pathways and T-cell antigen receptor (TCR)-related pathways. The replication of HIV-1 latent infection could be reactivated by pH1N1 infection through TCR and apoptotic pathways. These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways.",2016 Feb 2,"['Wang, Xue', 'Tan, Jiying', 'Biswas, Santanu', 'Zhao, Jiangqin', 'Devadas, Krishnakumar', 'Ye, Zhiping', 'Hewlett, Indira']",Viruses,,,False
67e43e9157face441254689d2bab22b781f6b989,PMC,The Role of HBZ in HTLV-1-Induced Oncogenesis,http://dx.doi.org/10.3390/v8020034,PMC4776189,26848677,CC BY,"Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and chronic inflammatory diseases. HTLV-1 bZIP factor (HBZ) is transcribed as an antisense transcript of the HTLV-1 provirus. Among the HTLV-1-encoded viral genes, HBZ is the only gene that is constitutively expressed in all ATL cases. Recent studies have demonstrated that HBZ plays an essential role in oncogenesis by regulating viral transcription and modulating multiple host factors, as well as cellular signaling pathways, that contribute to the development and continued growth of cancer. In this article, I summarize the current knowledge of the oncogenic function of HBZ in cell proliferation, apoptosis, T-cell differentiation, immune escape, and HTLV-1 pathogenesis.",2016 Feb 2,"Zhao, Tiejun",Viruses,,,True
f7b30ee89775bc82607cc6bc87feb5934b47625f,PMC,"Viruses Causing Gastroenteritis: The Known, The New and Those Beyond",http://dx.doi.org/10.3390/v8020042,PMC4776197,26867198,CC BY,"The list of recently discovered gastrointestinal viruses is expanding rapidly. Whether these agents are actually involved in a disease such as diarrhea is the essential question, yet difficult to answer. In this review a summary of all viruses found in diarrhea is presented, together with the current knowledge about their connection to disease.",2016 Feb 19,"['Oude Munnink, Bas B.', 'van der Hoek, Lia']",Viruses,,,True
21da52646864c1ad3303daf10f0b3e4c9d12fa5c,PMC,Structural Proteomics of Herpesviruses,http://dx.doi.org/10.3390/v8020050,PMC4776205,26907323,CC BY,"Herpesviruses are highly prevalent viruses associated with numerous pathologies both in animal and human populations. Until now, most of the strategies used to prevent or to cure these infections have been unsuccessful because these viruses have developed numerous immune evasion mechanisms. Therefore, a better understanding of their complex lifecycle is needed. In particular, while the genome of numerous herpesviruses has been sequenced, the exact composition of virions remains unknown for most of them. Mass spectrometry has recently emerged as a central method and has permitted fundamental discoveries in virology. Here, we review mass spectrometry-based approaches that have recently allowed a better understanding of the composition of the herpesvirus virion. In particular, we describe strategies commonly used for proper sample preparation and fractionation to allow protein localization inside the particle but also to avoid contamination by nonstructural proteins. A collection of other important data regarding post-translational modifications or the relative abundance of structural proteins is also described. This review also discusses the poorly studied importance of host proteins in herpesvirus structural proteins and the necessity to develop a quantitative workflow to better understand the dynamics of the structural proteome. In the future, we hope that this collaborative effort will assist in the development of new strategies to fight these infections.",2016 Feb 12,"['Leroy, Baptiste', 'Gillet, Laurent', 'Vanderplasschen, Alain', 'Wattiez, Ruddy']",Viruses,,,True
9c8a4fff809abaa0b5ede6a28db62da5edd082e1,PMC,Identification of Known and Novel Recurrent Viral Sequences in Data from Multiple Patients and Multiple Cancers,http://dx.doi.org/10.3390/v8020053,PMC4776208,26907326,CC BY,"Virus discovery from high throughput sequencing data often follows a bottom-up approach where taxonomic annotation takes place prior to association to disease. Albeit effective in some cases, the approach fails to detect novel pathogens and remote variants not present in reference databases. We have developed a species independent pipeline that utilises sequence clustering for the identification of nucleotide sequences that co-occur across multiple sequencing data instances. We applied the workflow to 686 sequencing libraries from 252 cancer samples of different cancer and tissue types, 32 non-template controls, and 24 test samples. Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method. We provide examples of identified inhabitants of the healthy tissue flora as well as experimental contaminants. Unmapped sequences that co-occur with high statistical significance potentially represent the unknown sequence space where novel pathogens can be identified.",2016 Feb 19,"['Friis-Nielsen, Jens', 'Kjartansdóttir, Kristín Rós', 'Mollerup, Sarah', 'Asplund, Maria', 'Mourier, Tobias', 'Jensen, Randi Holm', 'Hansen, Thomas Arn', 'Rey-Iglesia, Alba', 'Richter, Stine Raith', 'Nielsen, Ida Broman', 'Alquezar-Planas, David E.', 'Olsen, Pernille V. S.', 'Vinner, Lasse', 'Fridholm, Helena', 'Nielsen, Lars Peter', 'Willerslev, Eske', 'Sicheritz-Pontén, Thomas', 'Lund, Ole', 'Hansen, Anders Johannes', 'Izarzugaza, Jose M. G.', 'Brunak, Søren']",Viruses,,,True
d6a34d159840a3895ac1768920a1c498d3c448c6,PMC,Impact of Middle East Respiratory Syndrome coronavirus (MERS‐CoV) on pregnancy and perinatal outcome,http://dx.doi.org/10.1186/s12879-016-1437-y,PMC4776369,26936356,CC BY,"BACKGROUND: Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a viral respiratory disease. Most people infected with MERS-CoV develop severe acute respiratory illness. It was first reported in Saudi Arabia in 2012 and has since spread to several other countries. We report the clinical course of MERS-CoV infection in a pregnant woman who acquired the infection during the last trimester. CASE PRESENTATION: The patient is a 33-year-old female working as a critical care nurse. She was 32 weeks pregnant when she presented with respiratory symptoms after direct contact with a MERS-COV patient. Although the patient was in respiratory failure, necessitated mechanical ventilation, and intensive care (ICU) admission, a healthy infant was delivered. The mother recovered. To the best of our knowledge, this is the first reported case of a laboratory-confirmed Middle East Respiratory Syndrome Coronavirus in a pregnant woman. CONCLUSIONS: Middle East Respiratory Syndrome coronavirus (MERS-CoV) known to cause severe acute respiratory illness associated with a high risk of mortality Various factors may have contributed to the successful outcome of this patient such as young age, presentation during the last stages of pregnancy, and possible differences in immune response.",2016 Mar 2,"['Alserehi, Haleema', 'Wali, Ghassan', 'Alshukairi, Abeer', 'Alraddadi, Basem']",BMC Infect Dis,,,True
192e7d37cf521798de0394c2ad593f2bb77f5a77,PMC,"Obvious and Hidden Anxiety and the Related Factors in Operating Room Nurses Employed in General Hospital, Qazvin, Iran: A Cross-Sectional Study",http://dx.doi.org/10.5539/gjhs.v5n6p202,PMC4776884,24171889,CC BY,"BACKGROUND: Health promotion and security of manpower in a society is one of the pillars to progress a society. Anxiety, is the most common psychological disorder in societies and occupations like nursing, anesthesia technicians and operation room technicians. The aim of this study was to investigate prevalence of anxiety, and its severity in Iranian nurses working in operation room. Also, we determined the most important associated factors with anxiety. METHODS: In this cross sectional study, 152 nurses working in operating room participated. The tool to gather the data was a questionnaire, that included three parts; demographic information, obvious anxiety questions and hidden anxiety questions of Spielburger. Obtained data was analysed with SPSS 16 software. RESULTS: The majority of participants were females (94.7%) with experience at work less than 10 years (84.9%). The average scores of participants in obvious and hidden anxiety were 41.9±39.4 (range 20 to 75) and 39.4±8.2 (range 20 to 70), respectively. Anxiety level was significantly higher in females than males (P=0.04). The most prevalent cause of anxiety, was contact with infected biological factors (23% of nurses). The less important cause was concern about retirement (42.8% of nurses). CONCLUSION: Our results suggest that, anxiety disorders is prevalent in Iranian nurses working in public city hospitals, which warrants immediate programs for intervention to improve working situations in work place.",2013 Nov 29,"['Kayalha, Hamid', 'Yazdi, Zohreh', 'Rastak, Shahram', 'Dizaniha, Mojtaba']",Glob J Health Sci,,,True
1f7b47ec5e68a274a145bddd152303eba2f9d035,PMC,"Pandemic Influenza A (H1N1) and Its Prevention: A Cross Sectional Study on Patients’ Knowledge, Attitude and Practice among Patients Attending Primary Health Care Clinic in Kuala Lumpur, Malaysia",http://dx.doi.org/10.5539/gjhs.v4n2p95,PMC4777058,22980156,CC BY,"The World Health Organization confirmed that the novel influenza A, H1N1 as a pandemic on 11 June 2009. After less than three months, 182 countries were affected by the pandemic accounting for about 150,000 infected cases and 3000 mortality. Successful H1N1 pandemic management strategies’ shaped by making changes in health behavior. The aim of this study was to document patients’ knowledge, attitudes and practices (KAP) regarding the pandemic influenza A (H1N1) and its prevention. We performed a cross-sectional study on knowledge, attitudes and practices (KAP) on preventive measures of Influenza A (H1N1) involving 322 patients attending Klinik Kesihatan Jinjang, a primary health care clinic in Kuala Lumpur, Malaysia from May 10 to 26, 2010 using a face to face interview with a structured pre-tested questionnaire. The majority of the respondents were females (56.8%), Malays (43.2%) aged between 18-27 years old (28.9%). There were significant association between knowledge on the complication of H1N1, effectiveness of the treatment, preventive measures of Influenza A (H1N1) and race (p<0.001) and educational level (p<0.001). There were also significant associations between attitude scores of these patients and their gender (p=0.03), and educational level (p=0.001). Practice scores related to H1N1 were found to be significantly associated with race (p<0.001) and educational level (p<0.001). The significant associations were observed between knowledge and attitude (p<0.001), knowledge and practices (p<0.001), as well as attitude and practices related to H1N1 (p<0.001). Knowledge has a crucial effect on patients’ attitude and practice particularly in a pandemic spread. So health policy makers should attempt to disseminate information about preventive measures to community in order to improve their preventive practices during pandemics.",2012 Mar 1,"['Latiff, Latiffah A', 'Parhizkar, Saadat', 'Zainuddin, Huda', 'Chun, Goh M', 'Ramli, Mohammad Ali A Rahiman Nur Liyana N', 'Yun, Kerk L']",Glob J Health Sci,,,True
1b482a5e57ac1d83844e7204c907109483603516,PMC,High Prevalence and Putative Lineage Maintenance of Avian Coronaviruses in Scandinavian Waterfowl,http://dx.doi.org/10.1371/journal.pone.0150198,PMC4777420,26938459,CC BY,"Coronaviruses (CoVs) are found in a wide variety of wild and domestic animals, and constitute a risk for zoonotic and emerging infectious disease. In poultry, the genetic diversity, evolution, distribution and taxonomy of some coronaviruses have been well described, but little is known about the features of CoVs in wild birds. In this study we screened 764 samples from 22 avian species of the orders Anseriformes and Charadriiformes in Sweden collected in 2006/2007 for CoV, with an overall CoV prevalence of 18.7%, which is higher than many other wild bird surveys. The highest prevalence was found in the diving ducks—mainly Greater Scaup (Aythya marila; 51.5%)—and the dabbling duck Mallard (Anas platyrhynchos; 19.2%). Sequences from two of the Greater Scaup CoV fell into an infrequently detected lineage, shared only with a Tufted Duck (Aythya fuligula) CoV. Coronavirus sequences from Mallards in this study were highly similar to CoV sequences from the sample species and location in 2011, suggesting long-term maintenance in this population. A single Black-headed Gull represented the only positive sample from the order Charadriiformes. Globally, Anas species represent the largest fraction of avian CoV sequences, and there seems to be no host species, geographical or temporal structure. To better understand the eitiology, epidemiology and ecology of these viruses more systematic surveillance of wild birds and subsequent sequencing of detected CoV is imperative.",2016 Mar 3,"['Wille, Michelle', 'Muradrasoli, Shaman', 'Nilsson, Anna', 'Järhult, Josef D.']",PLoS One,,,True
1d13029ab155210da6e202f8cb5d902d7eabe226,PMC,"Epidemiological study of canine parvovirus infection in and around Bhubaneswar, Odisha, India",http://dx.doi.org/10.14202/vetworld.2015.33-37,PMC4777807,27046992,CC BY,"AIM: An epidemiological study of canine parvovirus infection in dogs in and around Bhubaneswar, Odisha was conducted between December 2012 to March 2013 and prevalence rate was studied on the basis of age, breed, and sex. MATERIALS AND METHODS: A total of 71 fecal samples from suspected diarrheic dogs were collected in sterile phosphate buffer saline (10% W/V) and examined by polymerase chain reaction (PCR) for detection of canine parvo virus infection, followed by epidemiological study in relation to age, breed, and sex. RESULTS: Of 71 samples analyzed, 29 (40.85%) were found to be positive by PCR assay. The infection was higher in Deshi/local breeds (34.48%), followed by German shepherd (17.24%), equal incidences in mixed and Labrador retriever (10.34%), Rottweiler and German spitz showed 6.90% each and finally lower incidences in four breeds (3.45%) such as Dalmatians, Nea politan mastiff, Pug and Great Dane. Age-wise prevalence study revealed the infection being more in the age group of 3-6 months (41.37%), followed by equal incidences of 27.59% in 1-3 months and 6-12 months age group, and a low incidence in age groups above 12 months (3.45%). The incidence was predominantly higher in males (86.21%) than females (13.79%). CONCLUSIONS: The epidemiological analysis revealed that the breed wise prevalence was found to be more in Deshi breeds as compared to others, age groups below 6 months were found to be more prone to parvovirus infection and males were mostly infected.",2015 Jan 9,"['Behera, Monalisa', 'Panda, S. K.', 'Sahoo, P. K.', 'Acharya, A. P.', 'Patra, R. C.', 'Das, Sweta', 'Pati, S.']",Vet World,,,True
8213f353876b2eba6110eae70dae057a2f08b93f,PMC,Long noncoding RNAs (lncRNAs) dynamics evidence immunomodulation during ISAV-Infected Atlantic salmon (Salmo salar),http://dx.doi.org/10.1038/srep22698,PMC4778034,26939752,CC BY,"Despite evidence for participation in the host response to infection, the roles of many long non-coding RNAs (lncRNAs) remain unknown. Therefore, the aims of this study were to identify lncRNAs in Atlantic salmon (Salmo salar) and evaluate their transcriptomic regulation during ISA virus (ISAV) infection, an Orthomyxoviridae virus associated with high mortalities in salmonid aquaculture. Using next-generation sequencing, whole-transcriptome analysis of the Salmo salar response to ISAV infection was performed, identifying 5,636 putative lncRNAs with a mean length of 695 base pairs. The transcriptional modulation evidenced a similar number of differentially expressed lncRNAs in the gills (3,294), head-kidney (3,275), and liver (3,325) over the course of the infection. Moreover, analysis of a subset of these lncRNAs showed the following: (i) Most were similarly regulated in response to ISA virus infection; (ii) The transcript subsets were uniquely modulated in each tissue (gills, liver, and head-kidney); and (iii) A subset of lncRNAs were upregulated for each tissue and time analysed, indicating potential markers for ISAV infection. These findings represent the first discovery of widespread differential expression of lncRNAs in response to virus infection in non-model species, suggesting that lncRNAs could be involved in regulating the host response during ISAV infection.",2016 Mar 4,"['Boltaña, Sebastian', 'Valenzuela-Miranda, Diego', 'Aguilar, Andrea', 'Mackenzie, Simon', 'Gallardo-Escárate, Cristian']",Sci Rep,,,True
08632feec28810500be75d2d1d2a6e287368cade,PMC,Long noncoding RNAs (lncRNAs) dynamics evidence immunomodulation during ISAV-Infected Atlantic salmon (Salmo salar),http://dx.doi.org/10.1038/srep22698,PMC4778034,26939752,CC BY,"Despite evidence for participation in the host response to infection, the roles of many long non-coding RNAs (lncRNAs) remain unknown. Therefore, the aims of this study were to identify lncRNAs in Atlantic salmon (Salmo salar) and evaluate their transcriptomic regulation during ISA virus (ISAV) infection, an Orthomyxoviridae virus associated with high mortalities in salmonid aquaculture. Using next-generation sequencing, whole-transcriptome analysis of the Salmo salar response to ISAV infection was performed, identifying 5,636 putative lncRNAs with a mean length of 695 base pairs. The transcriptional modulation evidenced a similar number of differentially expressed lncRNAs in the gills (3,294), head-kidney (3,275), and liver (3,325) over the course of the infection. Moreover, analysis of a subset of these lncRNAs showed the following: (i) Most were similarly regulated in response to ISA virus infection; (ii) The transcript subsets were uniquely modulated in each tissue (gills, liver, and head-kidney); and (iii) A subset of lncRNAs were upregulated for each tissue and time analysed, indicating potential markers for ISAV infection. These findings represent the first discovery of widespread differential expression of lncRNAs in response to virus infection in non-model species, suggesting that lncRNAs could be involved in regulating the host response during ISAV infection.",2016 Mar 4,"['Boltaña, Sebastian', 'Valenzuela-Miranda, Diego', 'Aguilar, Andrea', 'Mackenzie, Simon', 'Gallardo-Escárate, Cristian']",Sci Rep,,,False
71e40892b5ee0084f5953a80dcae63e68df725d9,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,True
7804648257929e923ff08509b4f1b2c7fd237ab0,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
41f85f8fa21f4d42179b4aaf63f48eb925c479bf,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
4baf7eab1e97a8135fb5b39f1d423bfb0ae4dd8b,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
5c6aa8d966729c4e0ed585493e6e048aa56cf2fc,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
60b5df62d05d96436a83ac05a6e8a6260840c5d8,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
4274448f43e86c8785db478d52788e0912b99f29,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
cb3b8b59e69f6ecea7174599a3f054d61e60c121,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
b0efffeef2a2a7d853e2e5be60e854050ad2ceb6,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
ed63a6725f27494b01ee2bc421e3ebf5bb11da97,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
01c1a483d6c189aa7dc3a833d8a1a80bc063165a,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
794bc58625ed326ad6230e5b1ea2beb5e6f0ec43,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
c7607aa9f76614af859fde6388979f58d5097361,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
24edf60956da0e015f00a5fbbd11fbdbcab16ff3,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
c46022b8376c55d77bf1e504feaa1e6c5e3ed626,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
f6b842b46c9678c37d60556963fc45f97074d56f,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
82273bf92042d6eb6962ab7bb2b4cea4c7a9ab20,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
7f481cf7a2c22bf5d565697c4631ee0da91412aa,PMC,The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.ppat.1005487,PMC4778874,26943817,CC BY,"Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.",2016 Mar 4,"['Zhao, Dianyuan', 'Han, Xintao', 'Zheng, Xuexing', 'Wang, Hualei', 'Yang, Zaopeng', 'Liu, Di', 'Han, Ke', 'Liu, Jing', 'Wang, Xiaowen', 'Yang, Wenting', 'Dong, Qingyang', 'Yang, Songtao', 'Xia, Xianzhu', 'Tang, Li', 'He, Fuchu']",PLoS Pathog,,,False
0c6dfd6796df35e619aa7b8099bd54174415fb52,PMC,"Improved Chiral Separation of (R,S)-Goitrin by SFC: An Application in Traditional Chinese Medicine",http://dx.doi.org/10.1155/2016/5782942,PMC4779522,27022502,CC BY,"Like chemical drugs, research and development of herbal medicine also have a need to resolve enantiomers. To help illustrating the antiviral bioactivity of Isatidis Radix, a widely used traditional Chinese medicine (TCM), supercritical fluid chromatography (SFC) was used for analytical and preparative separation of (R,S)-goitrin, which was reported as the active ingredient of the herbal. Improved resolution was achieved on Chiralpak IC column, using acetonitrile as the organic modifier, representing a tenfold increase in speed, compared to the previous normal phase HPLC (NPLC) method. The newly developed chromatographic method was validated in terms of linearity, precision, limit of detection (LOD), and limit of quantitation (LOQ). Scale-up purification of (R)-goitrin and (S)-goitrin was performed on a preparative column with >90% total recovery. The absolute stereochemical assignment of the purified isomers was determined through optical rotation study. This attempt explored SFC's application in chiral research of traditional Chinese medicine.",2016 Feb 21,"['Nie, Lixing', 'Dai, Zhong', 'Ma, Shuangcheng']",J Anal Methods Chem,,,True
4913c28e343a6cf2f8031799ff3b372e0e873bf5,PMC,Structure of Main Protease from Human Coronavirus NL63: Insights for Wide Spectrum Anti-Coronavirus Drug Design,http://dx.doi.org/10.1038/srep22677,PMC4780191,26948040,CC BY,"First identified in The Netherlands in 2004, human coronavirus NL63 (HCoV-NL63) was found to cause worldwide infections. Patients infected by HCoV-NL63 are typically young children with upper and lower respiratory tract infection, presenting with symptoms including croup, bronchiolitis, and pneumonia. Unfortunately, there are currently no effective antiviral therapy to contain HCoV-NL63 infection. CoV genomes encode an integral viral component, main protease (M(pro)), which is essential for viral replication through proteolytic processing of RNA replicase machinery. Due to the sequence and structural conservation among all CoVs, M(pro) has been recognized as an attractive molecular target for rational anti-CoV drug design. Here we present the crystal structure of HCoV-NL63 M(pro) in complex with a Michael acceptor inhibitor N3. Structural analysis, consistent with biochemical inhibition results, reveals the molecular mechanism of enzyme inhibition at the highly conservative substrate-recognition pocket. We show such molecular target remains unchanged across 30 clinical isolates of HCoV-NL63 strains. Through comparative study with M(pro)s from other human CoVs (including the deadly SARS-CoV and MERS-CoV) and their related zoonotic CoVs, our structure of HCoV-NL63 M(pro) provides critical insight into rational development of wide spectrum antiviral therapeutics to treat infections caused by human CoVs.",2016 Mar 7,"['Wang, Fenghua', 'Chen, Cheng', 'Tan, Wenjie', 'Yang, Kailin', 'Yang, Haitao']",Sci Rep,,,True
6600b6e7a6994f3b8e8d29bbea6b67ba198a36bc,PMC,Structure of Main Protease from Human Coronavirus NL63: Insights for Wide Spectrum Anti-Coronavirus Drug Design,http://dx.doi.org/10.1038/srep22677,PMC4780191,26948040,CC BY,"First identified in The Netherlands in 2004, human coronavirus NL63 (HCoV-NL63) was found to cause worldwide infections. Patients infected by HCoV-NL63 are typically young children with upper and lower respiratory tract infection, presenting with symptoms including croup, bronchiolitis, and pneumonia. Unfortunately, there are currently no effective antiviral therapy to contain HCoV-NL63 infection. CoV genomes encode an integral viral component, main protease (M(pro)), which is essential for viral replication through proteolytic processing of RNA replicase machinery. Due to the sequence and structural conservation among all CoVs, M(pro) has been recognized as an attractive molecular target for rational anti-CoV drug design. Here we present the crystal structure of HCoV-NL63 M(pro) in complex with a Michael acceptor inhibitor N3. Structural analysis, consistent with biochemical inhibition results, reveals the molecular mechanism of enzyme inhibition at the highly conservative substrate-recognition pocket. We show such molecular target remains unchanged across 30 clinical isolates of HCoV-NL63 strains. Through comparative study with M(pro)s from other human CoVs (including the deadly SARS-CoV and MERS-CoV) and their related zoonotic CoVs, our structure of HCoV-NL63 M(pro) provides critical insight into rational development of wide spectrum antiviral therapeutics to treat infections caused by human CoVs.",2016 Mar 7,"['Wang, Fenghua', 'Chen, Cheng', 'Tan, Wenjie', 'Yang, Kailin', 'Yang, Haitao']",Sci Rep,,,False
94fc08607ba07e9f5a0239d27251d4cdcc6bfd9a,PMC,Predominant Bacteria Detected from the Middle Ear Fluid of Children Experiencing Otitis Media: A Systematic Review,http://dx.doi.org/10.1371/journal.pone.0150949,PMC4783106,26953891,CC BY,"BACKGROUND: Otitis media (OM) is amongst the most common childhood diseases and is associated with multiple microbial pathogens within the middle ear. Global and temporal monitoring of predominant bacterial pathogens is important to inform new treatment strategies, vaccine development and to monitor the impact of vaccine implementation to improve progress toward global OM prevention. METHODS: A systematic review of published reports of microbiology of acute otitis media (AOM) and otitis media with effusion (OME) from January, 1970 to August 2014, was performed using PubMed databases. RESULTS: This review confirmed that Streptococcus pneumoniae and Haemophilus influenzae, remain the predominant bacterial pathogens, with S. pneumoniae the predominant bacterium in the majority reports from AOM patients. In contrast, H. influenzae was the predominant bacterium for patients experiencing chronic OME, recurrent AOM and AOM with treatment failure. This result was consistent, even where improved detection sensitivity from the use of polymerase chain reaction (PCR) rather than bacterial culture was conducted. On average, PCR analyses increased the frequency of detection of S. pneumoniae and H. influenzae 3.2 fold compared to culture, whilst Moraxella catarrhalis was 4.5 times more frequently identified by PCR. Molecular methods can also improve monitoring of regional changes in the serotypes and identification frequency of S. pneumoniae and H. influenzae over time or after vaccine implementation, such as after introduction of the 7-valent pneumococcal conjugate vaccine. CONCLUSIONS: Globally, S. pneumoniae and H. influenzae remain the predominant otopathogens associated with OM as identified through bacterial culture; however, molecular methods continue to improve the frequency and accuracy of detection of individual serotypes. Ongoing monitoring with appropriate detection methods for OM pathogens can support development of improved vaccines to provide protection from the complex combination of otopathogens within the middle ear, ultimately aiming to reduce the risk of chronic and recurrent OM in vulnerable populations.",2016 Mar 8,"['Ngo, Chinh C.', 'Massa, Helen M.', 'Thornton, Ruth B.', 'Cripps, Allan W.']",PLoS One,,,True
c07d89610bf10dbbc4124f1a65ffaab6855954ea,PMC,Monitoring Survivability and Infectivity of Porcine Epidemic Diarrhea Virus (PEDv) in the Infected On-Farm Earthen Manure Storages (EMS),http://dx.doi.org/10.3389/fmicb.2016.00265,PMC4783413,27014197,CC BY,"In recent years, porcine epidemic diarrhea virus (PEDv) has caused major epidemics, which has been a burden to North America’s swine industry. Low infectious dose and high viability in the environment are major challenges in eradication of this virus. To further understand the viability of PEDv in the infected manure, we longitudinally monitored survivability and infectivity of PEDv in two open earthen manure storages (EMS; previously referred to as lagoon) from two different infected swine farms identified in the province of Manitoba, Canada. Our study revealed that PEDv could survive up to 9 months in the infected EMS after the initial outbreak in the farm. The viral load varied among different layers of the EMS with an average of 1.1 × 10(5) copies/ml of EMS, independent of EMS temperature and pH. In both studied EMS, the evidence of viral replication was observed through increased viral load in the later weeks of the samplings while there was no new influx of infected manure into the EMS, which was suggestive of presence of potential alternative hosts for PEDv within the EMS. Decreasing infectivity of virus over time irrespective of increased viral load suggested the possibility of PEDv evolution within the EMS and perhaps in the new host that negatively impacted virus infectivity. Viral load in the top layer of the EMS was low and mostly non-infective suggesting that environmental factors, such as UV and sunlight, could diminish the replicability and infectivity of the virus. Thus, frequent agitation of the EMS that could expose virus to UV and sunlight might be a potential strategy for reduction of PEDv load and infectivity in the infected EMS.",2016 Mar 9,"['Tun, Hein M.', 'Cai, Zhangbin', 'Khafipour, Ehsan']",Front Microbiol,,,True
d634751b77c1f304d9dc2a979806013710333b2f,PMC,PEGylated substrates of NSP4 protease: A tool to study protease specificity,http://dx.doi.org/10.1038/srep22856,PMC4783772,26955973,CC BY,"Herein we present the synthesis of a novel type of peptidomimetics composed of repeating diaminopropionic acid residues modified with structurally diverse heterobifunctional polyethylene glycol chains (abbreviated as DAPEG). Based on the developed compounds, a library of fluorogenic substrates was synthesized. Further library deconvolution towards human neutrophil serine protease 4 (NSP4) yielded highly sensitive and selective internally quenched peptidomimetic substrates. In silico analysis of the obtained peptidomimetics revealed the presence of an interaction network with distant subsites located on the enzyme surface.",2016 Mar 9,"['Wysocka, Magdalena', 'Gruba, Natalia', 'Grzywa, Renata', 'Giełdoń, Artur', 'Bąchor, Remigiusz', 'Brzozowski, Krzysztof', 'Sieńczyk, Marcin', 'Dieter, Jenne', 'Szewczuk, Zbigniew', 'Rolka, Krzysztof', 'Lesner, Adam']",Sci Rep,,,True
84e5418129fec4b8872d40a2888a175550c0a6c6,PMC,PEGylated substrates of NSP4 protease: A tool to study protease specificity,http://dx.doi.org/10.1038/srep22856,PMC4783772,26955973,CC BY,"Herein we present the synthesis of a novel type of peptidomimetics composed of repeating diaminopropionic acid residues modified with structurally diverse heterobifunctional polyethylene glycol chains (abbreviated as DAPEG). Based on the developed compounds, a library of fluorogenic substrates was synthesized. Further library deconvolution towards human neutrophil serine protease 4 (NSP4) yielded highly sensitive and selective internally quenched peptidomimetic substrates. In silico analysis of the obtained peptidomimetics revealed the presence of an interaction network with distant subsites located on the enzyme surface.",2016 Mar 9,"['Wysocka, Magdalena', 'Gruba, Natalia', 'Grzywa, Renata', 'Giełdoń, Artur', 'Bąchor, Remigiusz', 'Brzozowski, Krzysztof', 'Sieńczyk, Marcin', 'Dieter, Jenne', 'Szewczuk, Zbigniew', 'Rolka, Krzysztof', 'Lesner, Adam']",Sci Rep,,,True
5fe3454a5e41a3e84b93a71a60d5aad0d81ce840,PMC,Human temperatures for syndromic surveillance in the emergency department: data from the autumn wave of the 2009 swine flu (H1N1) pandemic and a seasonal influenza outbreak,http://dx.doi.org/10.1186/s12873-016-0080-7,PMC4784270,26961277,CC BY,"BACKGROUND: The emergency department (ED) increasingly acts as a gateway to the evaluation and treatment of acute illnesses. Consequently, it has also become a key testing ground for systems that monitor and identify outbreaks of disease. Here, we describe a new technology that automatically collects body temperatures during triage. The technology was tested in an ED as an approach to monitoring diseases that cause fever, such as seasonal flu and some pandemics. METHODS: Temporal artery thermometers that log temperature measurements were placed in a Boston ED and used for initial triage vital signs. Time-stamped measurements were collected from the thermometers to investigate the performance a real-time system would offer. The data were summarized in terms of rates of fever (temperatures ≥100.4 °F [≥38.0 °C]) and were qualitatively compared with regional disease surveillance programs in Massachusetts. RESULTS: From September 2009 through August 2011, 71,865 body temperatures were collected and included in our analysis, 2073 (2.6 %) of which were fevers. The period of study included the autumn–winter wave of the 2009–2010 H1N1 (swine flu) pandemic, during which the weekly incidence of fever reached a maximum of 5.6 %, as well as the 2010–2011 seasonal flu outbreak, during which the maximum weekly incidence of fever was 6.6 %. The periods of peak fever rates corresponded with the periods of regionally elevated flu activity. CONCLUSIONS: Temperature measurements were monitored at triage in the ED over a period of 2 years. The resulting data showed promise as a potential surveillance tool for febrile disease that could complement current disease surveillance systems. Because temperature can easily be measured by non-experts, it might also be suitable for monitoring febrile disease activity in schools, workplaces, and transportation hubs, where many traditional syndromic indicators are impractical. However, the system’s validity and generalizability should be evaluated in additional years and settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12873-016-0080-7) contains supplementary material, which is available to authorized users.",2016 Mar 9,"['Bordonaro, Samantha F.', 'McGillicuddy, Daniel C.', 'Pompei, Francesco', 'Burmistrov, Dmitriy', 'Harding, Charles', 'Sanchez, Leon D.']",BMC Emerg Med,,,True
af98e90951bcd4faddf19d78fc4d228a111323e7,PMC,Human temperatures for syndromic surveillance in the emergency department: data from the autumn wave of the 2009 swine flu (H1N1) pandemic and a seasonal influenza outbreak,http://dx.doi.org/10.1186/s12873-016-0080-7,PMC4784270,26961277,CC BY,"BACKGROUND: The emergency department (ED) increasingly acts as a gateway to the evaluation and treatment of acute illnesses. Consequently, it has also become a key testing ground for systems that monitor and identify outbreaks of disease. Here, we describe a new technology that automatically collects body temperatures during triage. The technology was tested in an ED as an approach to monitoring diseases that cause fever, such as seasonal flu and some pandemics. METHODS: Temporal artery thermometers that log temperature measurements were placed in a Boston ED and used for initial triage vital signs. Time-stamped measurements were collected from the thermometers to investigate the performance a real-time system would offer. The data were summarized in terms of rates of fever (temperatures ≥100.4 °F [≥38.0 °C]) and were qualitatively compared with regional disease surveillance programs in Massachusetts. RESULTS: From September 2009 through August 2011, 71,865 body temperatures were collected and included in our analysis, 2073 (2.6 %) of which were fevers. The period of study included the autumn–winter wave of the 2009–2010 H1N1 (swine flu) pandemic, during which the weekly incidence of fever reached a maximum of 5.6 %, as well as the 2010–2011 seasonal flu outbreak, during which the maximum weekly incidence of fever was 6.6 %. The periods of peak fever rates corresponded with the periods of regionally elevated flu activity. CONCLUSIONS: Temperature measurements were monitored at triage in the ED over a period of 2 years. The resulting data showed promise as a potential surveillance tool for febrile disease that could complement current disease surveillance systems. Because temperature can easily be measured by non-experts, it might also be suitable for monitoring febrile disease activity in schools, workplaces, and transportation hubs, where many traditional syndromic indicators are impractical. However, the system’s validity and generalizability should be evaluated in additional years and settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12873-016-0080-7) contains supplementary material, which is available to authorized users.",2016 Mar 9,"['Bordonaro, Samantha F.', 'McGillicuddy, Daniel C.', 'Pompei, Francesco', 'Burmistrov, Dmitriy', 'Harding, Charles', 'Sanchez, Leon D.']",BMC Emerg Med,,,False
16673eca9ff4c1f57f53126415ad2f89b8cab557,PMC,Human temperatures for syndromic surveillance in the emergency department: data from the autumn wave of the 2009 swine flu (H1N1) pandemic and a seasonal influenza outbreak,http://dx.doi.org/10.1186/s12873-016-0080-7,PMC4784270,26961277,CC BY,"BACKGROUND: The emergency department (ED) increasingly acts as a gateway to the evaluation and treatment of acute illnesses. Consequently, it has also become a key testing ground for systems that monitor and identify outbreaks of disease. Here, we describe a new technology that automatically collects body temperatures during triage. The technology was tested in an ED as an approach to monitoring diseases that cause fever, such as seasonal flu and some pandemics. METHODS: Temporal artery thermometers that log temperature measurements were placed in a Boston ED and used for initial triage vital signs. Time-stamped measurements were collected from the thermometers to investigate the performance a real-time system would offer. The data were summarized in terms of rates of fever (temperatures ≥100.4 °F [≥38.0 °C]) and were qualitatively compared with regional disease surveillance programs in Massachusetts. RESULTS: From September 2009 through August 2011, 71,865 body temperatures were collected and included in our analysis, 2073 (2.6 %) of which were fevers. The period of study included the autumn–winter wave of the 2009–2010 H1N1 (swine flu) pandemic, during which the weekly incidence of fever reached a maximum of 5.6 %, as well as the 2010–2011 seasonal flu outbreak, during which the maximum weekly incidence of fever was 6.6 %. The periods of peak fever rates corresponded with the periods of regionally elevated flu activity. CONCLUSIONS: Temperature measurements were monitored at triage in the ED over a period of 2 years. The resulting data showed promise as a potential surveillance tool for febrile disease that could complement current disease surveillance systems. Because temperature can easily be measured by non-experts, it might also be suitable for monitoring febrile disease activity in schools, workplaces, and transportation hubs, where many traditional syndromic indicators are impractical. However, the system’s validity and generalizability should be evaluated in additional years and settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12873-016-0080-7) contains supplementary material, which is available to authorized users.",2016 Mar 9,"['Bordonaro, Samantha F.', 'McGillicuddy, Daniel C.', 'Pompei, Francesco', 'Burmistrov, Dmitriy', 'Harding, Charles', 'Sanchez, Leon D.']",BMC Emerg Med,,,True
9197060a4f302bde85b29584b40a2c75ba28f837,PMC,Conserved antigenic sites between MERS-CoV and Bat-coronavirus are revealed through sequence analysis,http://dx.doi.org/10.1186/s13029-016-0049-7,PMC4784407,26962326,CC BY,"BACKGROUND: MERS-CoV is a newly emerged human coronavirus reported closely related with HKU4 and HKU5 Bat coronaviruses. Bat and MERS corona-viruses are structurally related. Therefore, it is of interest to estimate the degree of conserved antigenic sites among them. It is of importance to elucidate the shared antigenic-sites and extent of conservation between them to understand the evolutionary dynamics of MERS-CoV. RESULTS: Multiple sequence alignment of the spike (S), membrane (M), enveloped (E) and nucleocapsid (N) proteins was employed to identify the sequence conservation among MERS and Bat (HKU4, HKU5) coronaviruses. We used various in silico tools to predict the conserved antigenic sites. We found that MERS-CoV shared 30 % of its S protein antigenic sites with HKU4 and 70 % with HKU5 bat-CoV. Whereas 100 % of its E, M and N protein’s antigenic sites are found to be conserved with those in HKU4 and HKU5. CONCLUSION: This sharing suggests that in case of pathogenicity MERS-CoV is more closely related to HKU5 bat-CoV than HKU4 bat-CoV. The conserved epitopes indicates their evolutionary relationship and ancestry of pathogenicity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13029-016-0049-7) contains supplementary material, which is available to authorized users.",2016 Mar 9,"['Sharmin, Refat', 'Islam, Abul B. M. M. K.']",Source Code Biol Med,,,True
be459dd25c7c6092a050c722c69ddd3d34ce0f94,PMC,Characterization and analysis of an infectious bronchitis virus strain isolated from southern China in 2013,http://dx.doi.org/10.1186/s12985-016-0497-3,PMC4784446,26955947,CC BY,"BACKGROUND: Infectious bronchitis is a severe disease caused by infectious bronchitis virus (IBV) that affects fowl flocks worldwide. The understanding of the mechanisms involved in IBV evolution and variation would provide important theoretical basis for prevention and control of the disease in the future. METHODS: IBV strain GD was isolated from southern China in 2013 and the complete genome sequencing and phylogenetic analysis were performed. RESULTS: The genome of approximately 27,680 nt comprised six genes, with insertions and mutations in most of the structural genes. The S1 gene showed the highest identity to strain TW2575/98 isolated in Taiwan, and was distantly related to the H120 vaccine strain. Phylogenetic analysis showed that the S1 gene of strain GD was also related to that of TW-type strains. Recombination analysis indicated that strain GD was a chimera whose putative parental strains belonged to the QX- and TW-type subgroups. CONCLUSIONS: An increasing number of TW-type strains have been isolated from China in recent years, which is in agreement with our findings, suggesting the emergence and increased prevalence of new TW-type strains in southern China.",2016 Mar 9,"['Xu, Gang', 'Liu, Xiao-yu', 'Zhao, Ye', 'Chen, Yang', 'Zhao, Jing', 'Zhang, Guo-zhong']",Virol J,,,True
4f67438d123ec1a0d283496cba0ad18fdc5c8e31,PMC,"Epidemiology, Seasonality and Treatment of Hospitalized Adults and Adolescents with Influenza in Jingzhou, China, 2010-2012",http://dx.doi.org/10.1371/journal.pone.0150713,PMC4784897,26958855,CC0,"BACKGROUND: After the 2009 influenza A (H1N1) pandemic, we conducted hospital-based severe acute respiratory infection (SARI) surveillance in one central Chinese city to assess disease burden attributable to influenza among adults and adolescents. METHODS: We defined an adult SARI case as a hospitalized patient aged ≥ 15 years with temperature ≥38.0°C and at least one of the following: cough, sore throat, tachypnea, difficulty breathing, abnormal breath sounds on auscultation, sputum production, hemoptysis, chest pain, or chest radiograph consistent with pneumonia. For each enrolled SARI case-patient, we completed a standardized case report form, and collected a nasopharyngeal swab within 24 hours of admission. Specimens were tested for influenza viruses by real-time reverse transcription polymerase chain reaction (rRT-PCR). We analyzed data from adult SARI cases in four hospitals in Jingzhou, China from April 2010 to April 2012. RESULTS: Of 1,790 adult SARI patients enrolled, 40% were aged ≥ 65 years old. The median duration of hospitalization was 9 days. Nearly all were prescribed antibiotics during their hospitalization, less than 1% were prescribed oseltamivir, and 28% were prescribed corticosteroids. Only 0.1% reported receiving influenza vaccination in the past year. Of 1,704 samples tested, 16% were positive for influenza. Influenza activity in all age groups showed winter-spring and summer peaks. Influenza-positive patients had a longer duration from illness onset to hospitalization and a shorter duration from hospital admission to discharge or death compared to influenza negative SARI patients. CONCLUSIONS: There is substantial burden of influenza-associated SARI hospitalizations in Jingzhou, China, especially among older adults. More effective promotion of annual seasonal influenza vaccination and timely oseltamivir treatment among high risk groups may improve influenza prevention and control in China.",2016 Mar 9,"['Zheng, Jiandong', 'Huo, Xixiang', 'Huai, Yang', 'Xiao, Lin', 'Jiang, Hui', 'Klena, John', 'Greene, Carolyn M.', 'Xing, Xuesen', 'Huang, Jigui', 'Liu, Shali', 'Peng, Youxing', 'Yang, Hui', 'Luo, Jun', 'Peng, Zhibin', 'Liu, Linlin', 'Chen, Maoyi', 'Chen, Hui', 'Zhang, Yuzhi', 'Huang, Danqin', 'Guan, Xuhua', 'Feng, Luzhao', 'Zhan, Faxian', 'Hu, Dale J.', 'Varma, Jay K.', 'Yu, Hongjie']",PLoS One,,,True
5306d1e54bdb040fea797ee3edbefe867ac400f5,PMC,Phylogenetic evidence for intratypic recombinant events in a novel human adenovirus C that causes severe acute respiratory infection in children,http://dx.doi.org/10.1038/srep23014,PMC4785336,26960434,CC BY,"Human adenoviruses (HAdVs) are prevalent in hospitalized children with severe acute respiratory infection (SARI). Here, we report a unique recombinant HAdV strain (CBJ113) isolated from a HAdV-positive child with SARI. The whole-genome sequence was determined using Sanger sequencing and high-throughput sequencing. A phylogenetic analysis of the complete genome indicated that the CBJ113 strain shares a common origin with HAdV-C2, HAdV-C6, HAdV-C1, HAdV-C5, and HAdV-C57 and formed a novel subclade on the same branch as other HAdV-C subtypes. BootScan and single nucleotide polymorphism analyses showed that the CBJ113 genome has an intra-subtype recombinant structure and comprises gene regions mainly originating from two circulating viral strains: HAdV-1 and HAdV-2. The parental penton base, pVI, and DBP genes of the recombinant strain clustered with the HAdV-1 prototype strain, and the E1B, hexon, fiber, and 100 K genes of the recombinant clustered within the HAdV-2 subtype, meanwhile the E4orf1 and DNA polymerase genes of the recombinant shared the greatest similarity with those of HAdV-5 and HAdV-6, respectively. All of these findings provide insight into our understanding of the dynamics of the complexity of the HAdV-C epidemic. More extensive studies should address the pathogenicity and clinical characteristics of the novel recombinant.",2016 Mar 10,"['Wang, Yanqun', 'Li, Yamin', 'Lu, Roujian', 'Zhao, Yanjie', 'Xie, Zhengde', 'Shen, Jun', 'Tan, Wenjie']",Sci Rep,,,True
3557b5b8c5052a1f7fbb18130ace9427201e0fe4,PMC,Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children,http://dx.doi.org/10.1371/journal.pone.0150776,PMC4786225,26964038,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. OBJECTIVE: The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. STUDY DESIGN: Between April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. RESULTS: We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients. CONCLUSION: Both SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified.",2016 Mar 10,"['Moesker, Fleur M.', 'van Kampen, Jeroen J. A.', 'van Rossum, Annemarie M. C.', 'de Hoog, Matthijs', 'Koopmans, Marion P. G.', 'Osterhaus, Albert D. M. E.', 'Fraaij, Pieter L. A.']",PLoS One,,,True
af0300839dd55d28a98c56af294244dcb5811000,PMC,Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children,http://dx.doi.org/10.1371/journal.pone.0150776,PMC4786225,26964038,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. OBJECTIVE: The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. STUDY DESIGN: Between April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. RESULTS: We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients. CONCLUSION: Both SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified.",2016 Mar 10,"['Moesker, Fleur M.', 'van Kampen, Jeroen J. A.', 'van Rossum, Annemarie M. C.', 'de Hoog, Matthijs', 'Koopmans, Marion P. G.', 'Osterhaus, Albert D. M. E.', 'Fraaij, Pieter L. A.']",PLoS One,,,False
8137902f849f58d6a3be9061630529af49f8ed98,PMC,Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children,http://dx.doi.org/10.1371/journal.pone.0150776,PMC4786225,26964038,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. OBJECTIVE: The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. STUDY DESIGN: Between April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. RESULTS: We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients. CONCLUSION: Both SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified.",2016 Mar 10,"['Moesker, Fleur M.', 'van Kampen, Jeroen J. A.', 'van Rossum, Annemarie M. C.', 'de Hoog, Matthijs', 'Koopmans, Marion P. G.', 'Osterhaus, Albert D. M. E.', 'Fraaij, Pieter L. A.']",PLoS One,,,False
4d754b08444d19e6df8559afad357bb13be89bd8,PMC,Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis,http://dx.doi.org/10.1371/journal.pone.0150861,PMC4786309,26963721,CC BY,"BACKGROUND: There is evidence to support a role for angiotensin (Ang) 1–7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study. METHODS: The colonic expression/activity profile of ACE2, Ang 1–7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence. The effect of either exogenous administration of Ang 1–7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model. RESULTS: Enhanced colonic expression of ACE2, Ang1-7 and MAS1-R was observed post-colitis induction. Daily Ang 1–7 treatment (0.01–0.06 mg/kg) resulted in significant amelioration of DSS-induced colitis. In contrast, daily administration of A779 significantly worsened features of colitis. Colitis-associated phosphorylation of p38, ERK1/2 and Akt was reduced by Ang 1–7 treatment. CONCLUSION: Our results indicate important anti-inflammatory actions of Ang 1–7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression.",2016 Mar 10,"['Khajah, Maitham A.', 'Fateel, Maryam M.', 'Ananthalakshmi, Kethireddy V.', 'Luqmani, Yunus A.']",PLoS One,,,True
9a4eb1665b578ba6744d7c2a62775379f6fcfc00,PMC,Understanding Spatio-Temporal Variability in the Reproduction Ratio of the Bluetongue (BTV-1) Epidemic in Southern Spain (Andalusia) in 2007 Using Epidemic Trees,http://dx.doi.org/10.1371/journal.pone.0151151,PMC4786328,26963397,CC BY,"Andalusia (Southern Spain) is considered one of the main routes of introduction of bluetongue virus (BTV) into Europe, evidenced by a devastating epidemic caused by BTV-1 in 2007. Understanding the pattern and the drivers of BTV-1 spread in Andalusia is critical for effective detection and control of future epidemics. A long-standing metric for quantifying the behaviour of infectious diseases is the case-reproduction ratio (R(t)), defined as the average number of secondary cases arising from a single infected case at time t (for t>0). Here we apply a method using epidemic trees to estimate the between-herd case reproduction ratio directly from epidemic data allowing the spatial and temporal variability in transmission to be described. We then relate this variability to predictors describing the hosts, vectors and the environment to better understand why the epidemic spread more quickly in some regions or periods. The R(t) value for the BTV-1 epidemic in Andalusia peaked in July at 4.6, at the start of the epidemic, then decreased to 2.2 by August, dropped below 1 by September (0.8), and by October it had decreased to 0.02. BTV spread was the consequence of both local transmission within established disease foci and BTV expansion to distant new areas (i.e. new foci), which resulted in a high variability in BTV transmission, not only among different areas, but particularly through time, which suggests that general control measures applied at broad spatial scales are unlikely to be effective. This high variability through time was probably due to the impact of temperature on BTV transmission, as evidenced by a reduction in the value of R(t) by 0.0041 for every unit increase (day) in the extrinsic incubation period (EIP), which is itself directly dependent on temperature. Moreover, within the range of values at which BTV-1 transmission occurred in Andalusia (20.6°C to 29.5°C) there was a positive correlation between temperature and R(t) values, although the relationship was not linear, probably as a result of the complex relationship between temperature and the different parameters affecting BTV transmission. R(t) values for BTV-1 in Andalusia fell below the threshold of 1 when temperatures dropped below 21°C, a much higher threshold than that reported in other BTV outbreaks, such as the BTV-8 epidemic in Northern Europe. This divergence may be explained by differences in the adaptation to temperature of the main vectors of the BTV-1 epidemic in Andalusia (Culicoides imicola) compared those of the BTV-8 epidemic in Northern Europe (Culicoides obsoletus). Importantly, we found that BTV transmission (R(t) value) increased significantly in areas with higher densities of sheep. Our analysis also established that control of BTV-1 in Andalusia was complicated by the simultaneous establishment of several distant foci at the start of the epidemic, which may have been caused by several independent introductions of infected vectors from the North of Africa. We discuss the implications of these findings for BTV surveillance and control in this region of Europe.",2016 Mar 10,"['Napp, S.', 'Allepuz, A.', 'Purse, B. V.', 'Casal, J.', 'García-Bocanegra, I.', 'Burgin, L. E.', 'Searle, K. R.']",PLoS One,,,True
3bd56ae4a76caf910da9be6266e18b74308364b6,PMC,Severe Community-Acquired Pneumonia Caused by Human Adenovirus in Immunocompetent Adults: A Multicenter Case Series,http://dx.doi.org/10.1371/journal.pone.0151199,PMC4788423,26967644,CC BY,"BACKGROUND: Severe community-acquired pneumonia (CAP) caused by human adenovirus (HAdV), especially HAdV type 55 (HAdV-55) in immunocompetent adults has raised increasing concerns. Clinical knowledge of severe CAP and acute respiratory distress syndrome induced by HAdV-55 is still limited, though the pathogen has been fully characterized by whole-genome sequencing. METHODS: We conducted a multicentre retrospective review of all consecutive patients with severe CAP caused by HAdV in immunocompetent adults admitted to the Emergency Department Intensive Care Unit of two hospitals in Northern China between February 2012 and April 2014. Clinical, laboratory, radiological characteristics, treatments and outcomes of these patients were collected and analyzed. RESULTS: A total of 15 consecutive severe CAP patients with laboratory-confirmed adenovirus infections were included. The median age was 30 years and all cases were identified during the winter and spring seasons. HAdV-55 was the most frequently (11/15) detected HAdV type. Persistent high fever, cough and rapid progression of dyspnea were typically reported in these patients. Significantly increased pneumonia severity index (PSI), respiratory rate, and lower PaO(2)/FiO(2), hypersensitive CRP were reported in non-survivors compared to survivors (P = 0.013, 0.022, 0.019 and 0.026, respectively). The rapid development of bilateral consolidations within 10 days after illness onset were the most common radiographic finding, usually accompanied by adjacent ground glass opacities and pleural effusions. Total mortality was 26.7% in this study. Corticosteroids were prescribed to 14 patients in this report, but the utilization rate between survivors and non-survivors was not significant. CONCLUSIONS: HAdV and the HAdV-55 sub-type play an important role among viral pneumonia pathogens in hospitalized immunocompetent adults in Northern China. HAdV should be tested in severe CAP patients with negative bacterial cultures and a lack of response to antibiotic treatment, even if radiologic imaging and clinical presentation initially suggest bacterial pneumonia.",2016 Mar 11,"['Tan, Dingyu', 'Zhu, Huadong', 'Fu, Yangyang', 'Tong, Fei', 'Yao, Dongqi', 'Walline, Joseph', 'Xu, Jun', 'Yu, Xuezhong']",PLoS One,,,True
430903f42d10ae8f5729df9a61e75e2d6dc09f65,PMC,Modeling the transboundary risk of feed ingredients contaminated with porcine epidemic diarrhea virus,http://dx.doi.org/10.1186/s12917-016-0674-z,PMC4788872,26968372,CC BY,"BACKGROUND: This study describes a model developed to evaluate the transboundary risk of PEDV-contaminated swine feed ingredients and the effect of two mitigation strategies during a simulated transport event from China to the US. RESULTS: Ingredients imported to the USA from China, including organic & conventional soybeans and meal, lysine hydrochloride, D-L methionine, tryptophan, Vitamins A, D & E, choline, carriers (rice hulls, corn cobs) and feed grade tetracycline, were inoculated with PEDV. Control ingredients, and treatments (ingredients plus a liquid antimicrobial (SalCURB, Kemin Industries (LA) or a 2 % custom medium chain fatty acid blend (MCFA)) were tested. The model ran for 37 days, simulating transport of cargo from Beijing, China to Des Moines, IA, US from December 23, 2012 to January 28, 2013. To mimic conditions on land and sea, historical temperature and percent relative humidity (% RH) data were programmed into an environmental chamber which stored all containers. To evaluate PEDV viability over time, ingredients were organized into 1 of 4 batches of samples, each batch representing a specific segment of transport. Batch 1 (segment 1) simulated transport of contaminated ingredients from manufacturing plants in Beijing (day 1 post-contamination (PC)). Batch 2 (segments 1 and 2) simulated manufacturing and delivery to Shanghai, including time in Anquing terminal awaiting shipment (days 1–8 PC). Batch 3 (segments 1, 2 and 3) represented time in China, the crossing of the Pacific and entry to the US at the San Francisco, CA terminal (day 1–27 PC). Batch 4 (segments 1–4) represented the previous events, including transport to Des Moines, IA (days 1–37 PC). Across control (non-treated) ingredients, viable PEDV was detected in soybean meal (organic and conventional), Vitamin D, lysine hydrochloride and choline chloride. In contrast, viable PEDV was not detected in any samples treated with LA or MCFA. CONCLUSIONS: These results demonstrate the ability of PEDV to survive in a subset of feed ingredients using a model simulating shipment from China to the US. This is proof of concept suggesting that contaminated feed ingredients could serve as transboundary risk factors for PEDV, along with the identification of effective mitigation options.",2016 Mar 12,"['Dee, Scott', 'Neill, Casey', 'Singrey, Aaron', 'Clement, Travis', 'Cochrane, Roger', 'Jones, Cassandra', 'Patterson, Gilbert', 'Spronk, Gordon', 'Christopher-Hennings, Jane', 'Nelson, Eric']",BMC Vet Res,,,True
35cd13c57dc46df01a1cae4ee1edbff7774cfe9b,PMC,Cytosolic Innate Immune Sensing and Signaling upon Infection,http://dx.doi.org/10.3389/fmicb.2016.00313,PMC4789553,27014235,CC BY,"Cytosolic sensing of pathogens is essential to a productive immune response. Recent reports have emphasized the importance of signaling platforms emanating from organelles and cytosolic sensors, particularly during the response to intracellular pathogens. Here, we highlight recent discoveries identifying the key mediators of nucleic acid and cyclic nucleotide sensing and discuss their importance in host defense. This review will also cover strategies evolved by pathogens to manipulate these pathways.",2016 Mar 14,"['Radoshevich, Lilliana', 'Dussurget, Olivier']",Front Microbiol,,,True
769d042233efa89198582de95656f0bb2198f379,PMC,Monitoring the Spread of Swine Enteric Coronavirus Diseases in the United States in the Absence of a Regulatory Framework,http://dx.doi.org/10.3389/fvets.2016.00018,PMC4789556,27014703,CC BY,"The reporting and monitoring of swine enteric coronavirus diseases (SECD), including porcine epidemic diarrhea virus and porcine delta coronavirus, in the United States have been challenging because of the initial absence of a regulatory framework and the emerging nature of these diseases. The National Animal Health Laboratory Network, the Emergency Management and Response System, and the Swine Health Monitoring Project were used to monitor the disease situation between May 2013 and March 2015. Important differences existed between and among them in terms of nature and extent of reporting. Here, we assess the implementation of these systems from different perspectives, including a description and comparison of collected data, disease metrics, usefulness, simplicity, flexibility, acceptability, representativeness, timeliness, and stability. This assessment demonstrates the limitations that the absence of premises identification imposes on certain animal health surveillance and response databases, and the importance of federally regulated frameworks in collecting accurate information in a timely manner. This study also demonstrates the value that the voluntary and producer-organized systems may have in monitoring emerging diseases. The results from all three data sources help to establish the baseline information on SECD epidemiological dynamics after almost 3 years of disease occurrence in the country.",2016 Mar 14,"['Perez, Andres M.', 'Alba, Anna', 'Goede, Dane', 'McCluskey, Brian', 'Morrison, Robert']",Front Vet Sci,,,True
56fb26305485a7d9c7844df6b25e30c8f1af4363,PMC,Epidemiological investigation of the 119th confirmed Middle East Respiratory Syndrome coronavirus case with an indefinite mode of transmission during the Pyeongtaek outbreak in Korea,http://dx.doi.org/10.4178/epih/e2015054,PMC4789606,26971695,CC BY,"Since the first case was diagnosed on May 20, 2015, there were 186 confirmed cases of Middle East Respiratory Syndrome (MERS) until the end of outbreak in South Korea. Although medical institutions were the most identifiable sources of MERS transmission in South Korea, similar to other countries, in-depth epidemiological investigation was required for some confirmed cases with indefinite contact history or hospital visit records. The subject of epidemiological investigation in the present study was a 35 year-old male patient diagnosed with MERS (#119) who lived in Asan-city and worked in Pyeongtaek-city. Various potential sources of transmission were carefully investigated. While he could have been exposed to MERS through a friend from Saudi Arabia or confirmed MERS cases in his workplace, neighboring areas, and medical institutions, as well as contacts in his home, the chances of transmission were low; however, the potential for transmission through his local community could not be excluded. Practically, it was difficult to determine the modes of transmission for all outbreak cases in communicable disease that occurred in this short period of time. The investigation to identify the mode of transmission in this case was ultimately unsuccessful. However, the various data collected and analyzed to reveal modes of transmission provided detailed information that could not be collected using only interview surveys.",2015 Dec 10,"['Choi, Jong Hyuk', 'Yoo, Byoungin', 'Lee, Soon Young', 'Lee, Eun Gyu', 'Ki, Moran', 'Lee, Woncheol', 'Jung, Jong Rak', 'Chang, Kyujin']",Epidemiol Health,,,True
6468e66c83046c44f33276aaf429c82fd2ef8cd0,PMC,Epidemiological investigation of the 119th confirmed Middle East Respiratory Syndrome coronavirus case with an indefinite mode of transmission during the Pyeongtaek outbreak in Korea,http://dx.doi.org/10.4178/epih/e2015054,PMC4789606,26971695,CC BY,"Since the first case was diagnosed on May 20, 2015, there were 186 confirmed cases of Middle East Respiratory Syndrome (MERS) until the end of outbreak in South Korea. Although medical institutions were the most identifiable sources of MERS transmission in South Korea, similar to other countries, in-depth epidemiological investigation was required for some confirmed cases with indefinite contact history or hospital visit records. The subject of epidemiological investigation in the present study was a 35 year-old male patient diagnosed with MERS (#119) who lived in Asan-city and worked in Pyeongtaek-city. Various potential sources of transmission were carefully investigated. While he could have been exposed to MERS through a friend from Saudi Arabia or confirmed MERS cases in his workplace, neighboring areas, and medical institutions, as well as contacts in his home, the chances of transmission were low; however, the potential for transmission through his local community could not be excluded. Practically, it was difficult to determine the modes of transmission for all outbreak cases in communicable disease that occurred in this short period of time. The investigation to identify the mode of transmission in this case was ultimately unsuccessful. However, the various data collected and analyzed to reveal modes of transmission provided detailed information that could not be collected using only interview surveys.",2015 Dec 10,"['Choi, Jong Hyuk', 'Yoo, Byoungin', 'Lee, Soon Young', 'Lee, Eun Gyu', 'Ki, Moran', 'Lee, Woncheol', 'Jung, Jong Rak', 'Chang, Kyujin']",Epidemiol Health,,,False
4e6e76a1940fbfadea1d88bbcbfe4f1554f7719b,PMC,Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging,http://dx.doi.org/10.1038/srep22952,PMC4789732,26972799,CC BY,"The specific packaging of the hepatitis C virus (HCV) genome is hypothesised to be driven by Core-RNA interactions. To identify the regions of the viral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential enrichment) to identify RNA aptamers which bind specifically to Core in vitro. Comparison of these aptamers to multiple HCV genomes revealed the presence of a conserved terminal loop motif within short RNA stem-loop structures. We postulated that interactions of these motifs, as well as sub-motifs which were present in HCV genomes at statistically significant levels, with the Core protein may drive virion assembly. We mutated 8 of these predicted motifs within the HCV infectious molecular clone JFH-1, thereby producing a range of mutant viruses predicted to possess altered RNA secondary structures. RNA replication and viral titre were unaltered in viruses possessing only one mutated structure. However, infectivity titres were decreased in viruses possessing a higher number of mutated regions. This work thus identified multiple novel RNA motifs which appear to contribute to genome packaging. We suggest that these structures act as cooperative packaging signals to drive specific RNA encapsidation during HCV assembly.",2016 Mar 14,"['Stewart, H.', 'Bingham, R.J.', 'White, S. J.', 'Dykeman, E. C.', 'Zothner, C.', 'Tuplin, A. K.', 'Stockley, P. G.', 'Twarock, R.', 'Harris, M.']",Sci Rep,,,True
399cef5a5c8ca96a0ac33ee31dec722eac145a7b,PMC,FLDS: A Comprehensive dsRNA Sequencing Method for Intracellular RNA Virus Surveillance,http://dx.doi.org/10.1264/jsme2.ME15171,PMC4791113,26877136,CC BY,"Knowledge of the distribution and diversity of RNA viruses is still limited in spite of their possible environmental and epidemiological impacts because RNA virus-specific metagenomic methods have not yet been developed. We herein constructed an effective metagenomic method for RNA viruses by targeting long double-stranded (ds)RNA in cellular organisms, which is a hallmark of infection, or the replication of dsRNA and single-stranded (ss)RNA viruses, except for retroviruses. This novel dsRNA targeting metagenomic method is characterized by an extremely high recovery rate of viral RNA sequences, the retrieval of terminal sequences, and uniform read coverage, which has not previously been reported in other metagenomic methods targeting RNA viruses. This method revealed a previously unidentified viral RNA diversity of more than 20 complete RNA viral genomes including dsRNA and ssRNA viruses associated with an environmental diatom colony. Our approach will be a powerful tool for cataloging RNA viruses associated with organisms of interest.",2016 Mar 13,"['Urayama, Syun-ichi', 'Takaki, Yoshihiro', 'Nunoura, Takuro']",Microbes Environ,,,True
97e8e782d5c99ab2e4fef7e8af54d77677ba6e3e,PMC,FLDS: A Comprehensive dsRNA Sequencing Method for Intracellular RNA Virus Surveillance,http://dx.doi.org/10.1264/jsme2.ME15171,PMC4791113,26877136,CC BY,"Knowledge of the distribution and diversity of RNA viruses is still limited in spite of their possible environmental and epidemiological impacts because RNA virus-specific metagenomic methods have not yet been developed. We herein constructed an effective metagenomic method for RNA viruses by targeting long double-stranded (ds)RNA in cellular organisms, which is a hallmark of infection, or the replication of dsRNA and single-stranded (ss)RNA viruses, except for retroviruses. This novel dsRNA targeting metagenomic method is characterized by an extremely high recovery rate of viral RNA sequences, the retrieval of terminal sequences, and uniform read coverage, which has not previously been reported in other metagenomic methods targeting RNA viruses. This method revealed a previously unidentified viral RNA diversity of more than 20 complete RNA viral genomes including dsRNA and ssRNA viruses associated with an environmental diatom colony. Our approach will be a powerful tool for cataloging RNA viruses associated with organisms of interest.",2016 Mar 13,"['Urayama, Syun-ichi', 'Takaki, Yoshihiro', 'Nunoura, Takuro']",Microbes Environ,,,False
77ce5438ade47650db78180cf5f4612db3e31c7b,PMC,"Dr. Wu Lien Teh, plague fighter and father of the Chinese public health system",http://dx.doi.org/10.1007/s13238-015-0238-1,PMC4791421,26825808,CC BY,,2016 Mar 29,"['Ma, Zhongliang', 'Li, Yanli']",Protein Cell,,,True
08741b63c08d63c1a86dd3ef3ce3d1bfd39e560b,PMC,"Dissection and integration of the autophagy signaling network initiated by bluetongue virus infection: crucial candidates ERK1/2, Akt and AMPK",http://dx.doi.org/10.1038/srep23130,PMC4791558,26976147,CC BY,"Bluetongue virus (BTV), a complex double-stranded segmented RNA virus, has been found to initiate cellular autophagy for its own benefit. Here, with a view to understanding the underlying mechanisms, we first systematically dissected the exact signaling network in BTV-induced autophagy. We found that the activity of mTOR, a crucial pivot, was inhibited by BTV1 infection, subsequently leading to downstream p70S6K suppression and autophagy initiation. We then explored the upstream regulators of mTOR and analyzed their activities via a series of assays. We found BTV1-induced autophagy to be independent of the ERK1/2 signaling pathway. However, the BTV1-induced inhibition of PI3K/Akt was found to be partially responsible for mTOR inactivation and subsequent autophagy initiation. Furthermore, we found unexpectedly that AMPK seemed to play a more important role in BTV1-induced autophagy. Elevated [Ca(2+)](cyto)-mediated activation of CaMKKβ exactly managed the activation of AMPK, which then positively regulated autophagy through suppressing mTOR. We must emphasize that TSC2 is a fatal mediator between upstream Akt or AMPK and downstream mTOR through its phosphorylation. Taken together, our data suggested that the BTV1-induced inhibition of the Akt-TSC2-mTOR pathway and the upregulation of the AMPK-TSC2-mTOR pathway both contributed to autophagy initiation and further favored virus replication.",2016 Mar 15,"['Lv, Shuang', 'Xu, Qing-Yuan', 'Sun, En-Cheng', 'Zhang, Ji-Kai', 'Wu, Dong-Lai']",Sci Rep,,,True
571625547b1603db0ad2f114822184a61f8e1b54,PMC,"Dissection and integration of the autophagy signaling network initiated by bluetongue virus infection: crucial candidates ERK1/2, Akt and AMPK",http://dx.doi.org/10.1038/srep23130,PMC4791558,26976147,CC BY,"Bluetongue virus (BTV), a complex double-stranded segmented RNA virus, has been found to initiate cellular autophagy for its own benefit. Here, with a view to understanding the underlying mechanisms, we first systematically dissected the exact signaling network in BTV-induced autophagy. We found that the activity of mTOR, a crucial pivot, was inhibited by BTV1 infection, subsequently leading to downstream p70S6K suppression and autophagy initiation. We then explored the upstream regulators of mTOR and analyzed their activities via a series of assays. We found BTV1-induced autophagy to be independent of the ERK1/2 signaling pathway. However, the BTV1-induced inhibition of PI3K/Akt was found to be partially responsible for mTOR inactivation and subsequent autophagy initiation. Furthermore, we found unexpectedly that AMPK seemed to play a more important role in BTV1-induced autophagy. Elevated [Ca(2+)](cyto)-mediated activation of CaMKKβ exactly managed the activation of AMPK, which then positively regulated autophagy through suppressing mTOR. We must emphasize that TSC2 is a fatal mediator between upstream Akt or AMPK and downstream mTOR through its phosphorylation. Taken together, our data suggested that the BTV1-induced inhibition of the Akt-TSC2-mTOR pathway and the upregulation of the AMPK-TSC2-mTOR pathway both contributed to autophagy initiation and further favored virus replication.",2016 Mar 15,"['Lv, Shuang', 'Xu, Qing-Yuan', 'Sun, En-Cheng', 'Zhang, Ji-Kai', 'Wu, Dong-Lai']",Sci Rep,,,False
bbed3cc036065a43e9da69ad09ce74d487b31c6b,PMC,Knowledge sharing during public health emergencies: from global call to effective implementation,http://dx.doi.org/10.2471/BLT.16.172650,PMC4794312,27034513,CC BY,,2016 Apr 1,"['Delaunay, Sophie', 'Kahn, Patricia', 'Tatay, Mercedes', 'Liu, Joanne']",Bull World Health Organ,,,True
f4aa788ab898b28b00ee103e4d4ab24a2c684caf,PMC,Venezuelan Equine Encephalitis Virus Induces Apoptosis through the Unfolded Protein Response Activation of EGR1,http://dx.doi.org/10.1128/JVI.02827-15,PMC4794670,26792742,CC BY,"Venezuelan equine encephalitis virus (VEEV) is a previously weaponized arthropod-borne virus responsible for causing acute and fatal encephalitis in animal and human hosts. The increased circulation and spread in the Americas of VEEV and other encephalitic arboviruses, such as eastern equine encephalitis virus and West Nile virus, underscore the need for research aimed at characterizing the pathogenesis of viral encephalomyelitis for the development of novel medical countermeasures. The host-pathogen dynamics of VEEV Trinidad donkey-infected human astrocytoma U87MG cells were determined by carrying out RNA sequencing (RNA-Seq) of poly(A) and mRNAs. To identify the critical alterations that take place in the host transcriptome following VEEV infection, samples were collected at 4, 8, and 16 h postinfection and RNA-Seq data were acquired using an Ion Torrent PGM platform. Differential expression of interferon response, stress response factors, and components of the unfolded protein response (UPR) was observed. The protein kinase RNA-like endoplasmic reticulum kinase (PERK) arm of the UPR was activated, as the expression of both activating transcription factor 4 (ATF4) and CHOP (DDIT3), critical regulators of the pathway, was altered after infection. Expression of the transcription factor early growth response 1 (EGR1) was induced in a PERK-dependent manner. EGR1(−/−) mouse embryonic fibroblasts (MEFs) demonstrated lower susceptibility to VEEV-induced cell death than isogenic wild-type MEFs, indicating that EGR1 modulates proapoptotic pathways following VEEV infection. The influence of EGR1 is of great importance, as neuronal damage can lead to long-term sequelae in individuals who have survived VEEV infection. IMPORTANCE Alphaviruses represent a group of clinically relevant viruses transmitted by mosquitoes to humans. In severe cases, viral spread targets neuronal tissue, resulting in significant and life-threatening inflammation dependent on a combination of virus-host interactions. Currently there are no therapeutics for infections cause by encephalitic alphaviruses due to an incomplete understanding of their molecular pathogenesis. Venezuelan equine encephalitis virus (VEEV) is an alphavirus that is prevalent in the Americas and that is capable of infecting horses and humans. Here we utilized next-generation RNA sequencing to identify differential alterations in VEEV-infected astrocytes. Our results indicated that the abundance of transcripts associated with the interferon and the unfolded protein response pathways was altered following infection and demonstrated that early growth response 1 (EGR1) contributed to VEEV-induced cell death.",2016 Mar 11,"['Baer, Alan', 'Lundberg, Lindsay', 'Swales, Danielle', 'Waybright, Nicole', 'Pinkham, Chelsea', 'Dinman, Jonathan D.', 'Jacobs, Jonathan L.', 'Kehn-Hall, Kylene']",J Virol,,,True
9301787667eb36e650623c8dc753399f3e1b4b7c,PMC,A Next-Generation Sequencing Data Analysis Pipeline for Detecting Unknown Pathogens from Mixed Clinical Samples and Revealing Their Genetic Diversity,http://dx.doi.org/10.1371/journal.pone.0151495,PMC4795770,26986479,CC BY,"Forty-two cytopathic effect (CPE)-positive isolates were collected from 2008 to 2012. All isolates could not be identified for known viral pathogens by routine diagnostic assays. They were pooled into 8 groups of 5–6 isolates to reduce the sequencing cost. Next-generation sequencing (NGS) was conducted for each group of mixed samples, and the proposed data analysis pipeline was used to identify viral pathogens in these mixed samples. Polymerase chain reaction (PCR) or enzyme-linked immunosorbent assay (ELISA) was individually conducted for each of these 42 isolates depending on the predicted viral types in each group. Two isolates remained unknown after these tests. Moreover, iteration mapping was implemented for each of these 2 isolates, and predicted human parechovirus (HPeV) in both. In summary, our NGS pipeline detected the following viruses among the 42 isolates: 29 human rhinoviruses (HRVs), 10 HPeVs, 1 human adenovirus (HAdV), 1 echovirus and 1 rotavirus. We then focused on the 10 identified Taiwanese HPeVs because of their reported clinical significance over HRVs. Their genomes were assembled and their genetic diversity was explored. One novel 6-bp deletion was found in one HPeV-1 virus. In terms of nucleotide heterogeneity, 64 genetic variants were detected from these HPeVs using the mapped NGS reads. Most importantly, a recombination event was found between our HPeV-3 and a known HPeV-4 strain in the database. Similar event was detected in the other HPeV-3 strains in the same clade of the phylogenetic tree. These findings demonstrated that the proposed NGS data analysis pipeline identified unknown viruses from the mixed clinical samples, revealed their genetic identity and variants, and characterized their genetic features in terms of viral evolution.",2016 Mar 17,"['Gong, Yu-Nong', 'Chen, Guang-Wu', 'Yang, Shu-Li', 'Lee, Ching-Ju', 'Shih, Shin-Ru', 'Tsao, Kuo-Chien']",PLoS One,,,True
2274f85a6caf5b13844080f9ec45cc7d01f8f952,PMC,A Next-Generation Sequencing Data Analysis Pipeline for Detecting Unknown Pathogens from Mixed Clinical Samples and Revealing Their Genetic Diversity,http://dx.doi.org/10.1371/journal.pone.0151495,PMC4795770,26986479,CC BY,"Forty-two cytopathic effect (CPE)-positive isolates were collected from 2008 to 2012. All isolates could not be identified for known viral pathogens by routine diagnostic assays. They were pooled into 8 groups of 5–6 isolates to reduce the sequencing cost. Next-generation sequencing (NGS) was conducted for each group of mixed samples, and the proposed data analysis pipeline was used to identify viral pathogens in these mixed samples. Polymerase chain reaction (PCR) or enzyme-linked immunosorbent assay (ELISA) was individually conducted for each of these 42 isolates depending on the predicted viral types in each group. Two isolates remained unknown after these tests. Moreover, iteration mapping was implemented for each of these 2 isolates, and predicted human parechovirus (HPeV) in both. In summary, our NGS pipeline detected the following viruses among the 42 isolates: 29 human rhinoviruses (HRVs), 10 HPeVs, 1 human adenovirus (HAdV), 1 echovirus and 1 rotavirus. We then focused on the 10 identified Taiwanese HPeVs because of their reported clinical significance over HRVs. Their genomes were assembled and their genetic diversity was explored. One novel 6-bp deletion was found in one HPeV-1 virus. In terms of nucleotide heterogeneity, 64 genetic variants were detected from these HPeVs using the mapped NGS reads. Most importantly, a recombination event was found between our HPeV-3 and a known HPeV-4 strain in the database. Similar event was detected in the other HPeV-3 strains in the same clade of the phylogenetic tree. These findings demonstrated that the proposed NGS data analysis pipeline identified unknown viruses from the mixed clinical samples, revealed their genetic identity and variants, and characterized their genetic features in terms of viral evolution.",2016 Mar 17,"['Gong, Yu-Nong', 'Chen, Guang-Wu', 'Yang, Shu-Li', 'Lee, Ching-Ju', 'Shih, Shin-Ru', 'Tsao, Kuo-Chien']",PLoS One,,,False
6bffaf7e11f81818a630ae32f752c963664bdc71,PMC,A Modified Coupled Spectrophotometric Method to Detect 2-5 Oligoadenylate Synthetase Activity in Prostate Cell Lines,http://dx.doi.org/10.1186/s12575-016-0038-x,PMC4797170,26997919,CC BY,"BACKGROUND: 2’-5’ oligoadenylate synthetases (OAS) are interferon inducible enzymes that polymerizes ATP to 2’-5’-linked oligomers of adenylate (2-5As). As part of the innate immune response, these enzymes are activated by viral double stranded RNA or mRNAs with significant double stranded structure. The 2-5As in turn activate RNaseL that degrade single stranded RNAs. Three distinct forms of OAS exist in human cells (OAS1, 2 and 3) with each form having multiple spliced variants. The OAS enzymes and their spliced variants have different enzyme activities. OAS enzymes also play a significant role in regulating multiple cellular processes such as proliferation and apoptosis. Moreover, Single nucleotide polymorphisms that alter OAS activity are also associated with viral infection, diabetes and cancer. Thus detection of OAS enzyme activity with a simple spectrophotometric method in cells will be important in clinical research. RESULTS: Here we propose a modified coupled spectrophotometric assay to detect 2-5 oligoadenylate synthetase (OAS) enzyme activity in prostate cell lines as a model system. The OAS enzyme from prostate cancer cell lysates was purified using Polyinosinic: polycytidylic acid (poly I:C) bound activated sepharose beads. The activated OAS enzyme eluted from Sepharose beads showed expression of p46 isoform of OAS1, generally considered the most abundant OAS isoform in elutes from DU14 cell line but not in other prostate cell line. In this assay the phosphates generated by the OAS enzymatic reaction is coupled with conversion of the substrate 2-amino-6-mercapto-7-methylpurine ribonucleoside (methylthioguanosine, a guanosine analogue; MESG) to a purine base product, 2-amino-6-mercapto-7-methylpurine and ribose1-phosphate via a catalyst purine nucleoside phosphorylase (phosphorylase) using a commercially available pyrophosphate kit. The absorbance of the purine base product is measured at 360 nm. The higher levels of phosphates detected in DU145 cell line indicates more activity of OAS in this prostate cancer cell line. CONCLUSION: The modified simple method detected OAS enzyme activity with sensitivity and specificity, which could help in detection of OAS enzymes avoiding the laborious and radioactive methods.",2016 Mar 17,"['Bhosle, Sushma M.', 'Hunt, Aisha', 'Chaudhary, Jaideep']",Biol Proced Online,,,True
09f23fe560ba923e5960707d0b4451df85253b36,PMC,Comparative analysis of routes of immunization of a live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in a heterologous virus challenge study,http://dx.doi.org/10.1186/s13567-016-0331-3,PMC4797253,26988085,CC BY,"Porcine reproductive and respiratory syndrome (PRRS) is caused by PRRS virus (PRRSV), which infects primarily the respiratory tract of pigs. Thus intranasal (IN) delivery of a potent vaccine-adjuvant formulation is promising. In this study, PRRS-MLV (VR2332) was coadministered ± an adjuvant Mycobacterium vaccae whole cell lysate or CpG ODN through intramuscular (IM) or IN route as a mist, and challenged with a heterologous PRRSV 1-4-4 IN at 42 days post-vaccination (dpv). At 14 and 26 dpv, vaccine viral RNA copies were one log greater in the plasma of PRRS-MLV IM compared to IN vaccinated pigs, and the infectious replicating vaccine virus was detected only in the IM group. In PRRS-MLV ± adjuvant IM vaccinated pigs, reduced viral RNA load and absence of the replicating challenged virus was observed at 7, 10 and 14 days post-challenge (dpc). At 14 dpc, in BAL fluid ≥5 log viral RNA copies were detected in all the pig groups, but the replicating challenged virus was undetectable only in IM groups. Immunologically, virus neutralizing antibody titers in the plasma of IM (but not IN) vaccine groups was ≥8 against the vaccine and challenged viruses. At 26 dpv, PRRS-MLV IM (without adjuvant) received pigs had significantly increased population of CD4 and CD8 T cells in PBMC. At 14 dpc, relatively increased population of IFN-γ(+) total lymphocytes, NK, CD4, CD8 and γδ T cells were observed in the MLV-IM group. In conclusion, PRRS-MLV IM vaccination induced the virus specific T cell response in pigs, but still it is required to improve its cross-protective efficacy.",2016 Mar 17,"['Ouyang, Kang', 'Hiremath, Jagadish', 'Binjawadagi, Basavaraj', 'Shyu, Duan-Liang', 'Dhakal, Santosh', 'Arcos, Jesus', 'Schleappi, Rose', 'Holman, Lynette', 'Roof, Michael', 'Torrelles, Jordi B.', 'Renukaradhya, Gourapura J.']",Vet Res,,,True
63db9e65e1430b32da0f2f3d88fd45ce88eaab31,PMC,Training on the care of patients with respiratory syndrome of middle east-coronavirus and ebola virus based on clinical simulation,http://dx.doi.org/10.1186/2197-425X-3-S1-A732,PMC4798186,,CC BY,,2015 Oct 1,"['Palamidessi Domínguez, J', 'Valdivia de la Fuente, M', 'Rubio Muñoz, JJ', 'Alcántara Carmona, S', 'Palacios Castañeda, D', 'Martínez Sanz, N', 'Lobo Valbuena, B', 'Fernández Rivas, R', 'Pérez Lucendo, A', 'Pérez Pérez, L']",Intensive Care Med Exp,,,False
bfdf1cc025285b3c20fdde66f5de3be60b46930e,PMC,Locally Produced IL-10 Limits Cutaneous Vaccinia Virus Spread,http://dx.doi.org/10.1371/journal.ppat.1005493,PMC4798720,26991092,CC0,"Skin infection with the poxvirus vaccinia (VV) elicits a powerful, inflammatory cellular response that clears virus infection in a coordinated, spatially organized manner. Given the high concentration of pro-inflammatory effectors at areas of viral infection, it is unclear how tissue pathology is limited while virus-infected cells are being eliminated. To better understand the spatial dynamics of the anti-inflammatory response to a cutaneous viral infection, we first screened cytokine mRNA expression levels after epicutaneous (ec.) VV infection and found a large increase the anti-inflammatory cytokine IL-10. Ex vivo analyses revealed that T cells in the skin were the primary IL-10-producing cells. To understand the distribution of IL-10-producing T cells in vivo, we performed multiphoton intravital microscopy (MPM) of VV-infected mice, assessing the location and dynamic behavior of IL-10 producing cells. Although virus-specific T cells were distributed throughout areas of the inflamed skin lacking overt virus-infection, IL-10(+) cells closely associated with large keratinocytic foci of virus replication where they exhibited similar motility patterns to bulk antigen-specific CD8(+) T cells. Paradoxically, neutralizing secreted IL-10 in vivo with an anti-IL-10 antibody increased viral lesion size and viral replication. Additional analyses demonstrated that IL-10 antibody administration decreased recruitment of CCR2(+) inflammatory monocytes, which were important for reducing viral burden in the infected skin. Based upon these findings, we conclude that spatially concentrated IL-10 production limits cutaneous viral replication and dissemination, likely through modulation of the innate immune repertoire at the site of viral growth.",2016 Mar 18,"['Cush, Stephanie S.', 'Reynoso, Glennys V.', 'Kamenyeva, Olena', 'Bennink, Jack R.', 'Yewdell, Jonathan W.', 'Hickman, Heather D.']",PLoS Pathog,,,True
db7ddc7b6e1689aed55b17716e2c2d3309b56f90,PMC,The role of respiratory viruses in the etiology of bacterial pneumonia: An ecological perspective,http://dx.doi.org/10.1093/emph/eow007,PMC4801059,26884414,CC BY,"Pneumonia is the leading cause of death among children less than 5 years old worldwide. A wide range of viral, bacterial and fungal agents can cause pneumonia: although viruses are the most common etiologic agent, the severity of clinical symptoms associated with bacterial pneumonia and increasing antibiotic resistance makes bacterial pneumonia a major public health concern. Bacterial pneumonia can follow upper respiratory viral infection and complicate lower respiratory viral infection. Secondary bacterial pneumonia is a major cause of influenza-related deaths. In this review, we evaluate the following hypotheses: (i) respiratory viruses influence the etiology of pneumonia by altering bacterial community structure in the upper respiratory tract (URT) and (ii) respiratory viruses promote or inhibit colonization of the lower respiratory tract (LRT) by certain bacterial species residing in the URT. We conducted a systematic review of the literature to examine temporal associations between respiratory viruses and bacteria and a targeted review to identify potential mechanisms of interactions. We conclude that viruses both alter the bacterial community in the URT and promote bacterial colonization of the LRT. However, it is uncertain whether changes in the URT bacterial community play a substantial role in pneumonia etiology. The exception is Streptococcus pneumoniae where a strong link between viral co-infection, increased carriage and pneumococcal pneumonia has been established.",2016 Feb 15,"['Lee, Kyu Han', 'Gordon, Aubree', 'Foxman, Betsy']",Evol Med Public Health,,,True
7dc5c4c3a782bb77aaa9f3e03f16f7fa703cfd54,PMC,Evaluation of recombinase polymerase amplification for detection of begomoviruses by plant diagnostic clinics,http://dx.doi.org/10.1186/s12985-016-0504-8,PMC4802622,27000806,CC BY,"BACKGROUND: Plant viruses in the genus Begomovirus, family Geminiviridae often cause substantial crop losses. These viruses have been emerging in many locations throughout the tropics and subtropics. Like many plant viruses, they are often not recognized by plant diagnostic clinics due in large part to the lack of rapid and cost effective assays. An isothermal amplification assay, Recombinase polymerase amplification (RPA), was evaluated for its ability to detect three begomoviruses and for its suitability for use in plant diagnostic clinics. Methods for DNA extraction and separation of amplicons from proteins used in the assay were modified and compared to RPA manufacturer’s protocols. The modified RPA assays were compared to PCR assays for sensitivity, use in downstream applications, cost, and speed. RESULTS: Recombinase polymerase amplification (RPA) assays for the detection of Bean golden yellow mosaic virus, Tomato mottle virus and Tomato yellow leaf curl virus (TYLCV) were specific, only amplifying the target viruses in three different host species. RPA was able to detect the target virus when the template was in a crude extract generated using a simple inexpensive extraction method, while PCR was not. Separation of RPA-generated amplicons from DNA-binding proteins could be accomplished by several methods, all of which were faster and less expensive than that recommended by the manufacturer. Use of these modifications resulted in an RPA assay that was faster than PCR but with a similar reagent cost. This modified RPA was the more cost effective assay when labor is added to the cost since RPA can be performed much faster than PCR. RPA had a sensitivity approximate to that of ELISA when crude extract was used as template. RPA-generated amplicons could be used in downstream applications (TA cloning, digestion with a restriction endonuclease, direct sequencing) similar to PCR but unlike some other isothermal reactions. CONCLUSIONS: RPA could prove useful for the cost effective detection of plant viruses by plant diagnostic clinics. It can be performed in one hour or less with a reagent cost similar to that of PCR but with a lower labor cost, and with an acceptable level of sensitivity and specificity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0504-8) contains supplementary material, which is available to authorized users.",2016 Mar 22,"['Londoño, Maria A.', 'Harmon, Carrie L.', 'Polston, Jane E.']",Virol J,,,False
2e5b75124a437e9592822b4ece85c99f34021fc5,PMC,Evaluation of recombinase polymerase amplification for detection of begomoviruses by plant diagnostic clinics,http://dx.doi.org/10.1186/s12985-016-0504-8,PMC4802622,27000806,CC BY,"BACKGROUND: Plant viruses in the genus Begomovirus, family Geminiviridae often cause substantial crop losses. These viruses have been emerging in many locations throughout the tropics and subtropics. Like many plant viruses, they are often not recognized by plant diagnostic clinics due in large part to the lack of rapid and cost effective assays. An isothermal amplification assay, Recombinase polymerase amplification (RPA), was evaluated for its ability to detect three begomoviruses and for its suitability for use in plant diagnostic clinics. Methods for DNA extraction and separation of amplicons from proteins used in the assay were modified and compared to RPA manufacturer’s protocols. The modified RPA assays were compared to PCR assays for sensitivity, use in downstream applications, cost, and speed. RESULTS: Recombinase polymerase amplification (RPA) assays for the detection of Bean golden yellow mosaic virus, Tomato mottle virus and Tomato yellow leaf curl virus (TYLCV) were specific, only amplifying the target viruses in three different host species. RPA was able to detect the target virus when the template was in a crude extract generated using a simple inexpensive extraction method, while PCR was not. Separation of RPA-generated amplicons from DNA-binding proteins could be accomplished by several methods, all of which were faster and less expensive than that recommended by the manufacturer. Use of these modifications resulted in an RPA assay that was faster than PCR but with a similar reagent cost. This modified RPA was the more cost effective assay when labor is added to the cost since RPA can be performed much faster than PCR. RPA had a sensitivity approximate to that of ELISA when crude extract was used as template. RPA-generated amplicons could be used in downstream applications (TA cloning, digestion with a restriction endonuclease, direct sequencing) similar to PCR but unlike some other isothermal reactions. CONCLUSIONS: RPA could prove useful for the cost effective detection of plant viruses by plant diagnostic clinics. It can be performed in one hour or less with a reagent cost similar to that of PCR but with a lower labor cost, and with an acceptable level of sensitivity and specificity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0504-8) contains supplementary material, which is available to authorized users.",2016 Mar 22,"['Londoño, Maria A.', 'Harmon, Carrie L.', 'Polston, Jane E.']",Virol J,,,False
3e3dc81c5985a37a950e4f63ffa10f4d5f9581aa,PMC,Evaluation of recombinase polymerase amplification for detection of begomoviruses by plant diagnostic clinics,http://dx.doi.org/10.1186/s12985-016-0504-8,PMC4802622,27000806,CC BY,"BACKGROUND: Plant viruses in the genus Begomovirus, family Geminiviridae often cause substantial crop losses. These viruses have been emerging in many locations throughout the tropics and subtropics. Like many plant viruses, they are often not recognized by plant diagnostic clinics due in large part to the lack of rapid and cost effective assays. An isothermal amplification assay, Recombinase polymerase amplification (RPA), was evaluated for its ability to detect three begomoviruses and for its suitability for use in plant diagnostic clinics. Methods for DNA extraction and separation of amplicons from proteins used in the assay were modified and compared to RPA manufacturer’s protocols. The modified RPA assays were compared to PCR assays for sensitivity, use in downstream applications, cost, and speed. RESULTS: Recombinase polymerase amplification (RPA) assays for the detection of Bean golden yellow mosaic virus, Tomato mottle virus and Tomato yellow leaf curl virus (TYLCV) were specific, only amplifying the target viruses in three different host species. RPA was able to detect the target virus when the template was in a crude extract generated using a simple inexpensive extraction method, while PCR was not. Separation of RPA-generated amplicons from DNA-binding proteins could be accomplished by several methods, all of which were faster and less expensive than that recommended by the manufacturer. Use of these modifications resulted in an RPA assay that was faster than PCR but with a similar reagent cost. This modified RPA was the more cost effective assay when labor is added to the cost since RPA can be performed much faster than PCR. RPA had a sensitivity approximate to that of ELISA when crude extract was used as template. RPA-generated amplicons could be used in downstream applications (TA cloning, digestion with a restriction endonuclease, direct sequencing) similar to PCR but unlike some other isothermal reactions. CONCLUSIONS: RPA could prove useful for the cost effective detection of plant viruses by plant diagnostic clinics. It can be performed in one hour or less with a reagent cost similar to that of PCR but with a lower labor cost, and with an acceptable level of sensitivity and specificity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0504-8) contains supplementary material, which is available to authorized users.",2016 Mar 22,"['Londoño, Maria A.', 'Harmon, Carrie L.', 'Polston, Jane E.']",Virol J,,,True
3e6c85e4e3409c135ec4d5525290a9908aac2b58,PMC,Actin- and clathrin-dependent mechanisms regulate interferon gamma release after stimulation of human immune cells with respiratory syncytial virus,http://dx.doi.org/10.1186/s12985-016-0506-6,PMC4802911,27004689,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) can cause recurrent and severe respiratory tract infections. Cytoskeletal proteins are often involved during viral infections, either for cell entry or the initiation of the immune response. The importance of actin and clathrin dynamics for cell entry and the initiation of the cellular immune response against RSV in human immune cells is not known yet. The aim of this study was to investigate the role of actin and clathrin on cell entry of RSV and the subsequent effect on T cell activation and interferon gamma release in human immune cells. METHODS: Peripheral blood mononuclear cells and purified monocytes were isolated from healthy adults and stimulated in vitro with RSV. Actin and clathrin dynamics were inhibited with respectively cytochalasin D and chlorpromazine. T cell receptor signaling was inhibited with cyclosporin A. Flow cytometry was used to determine the role of actin and clathrin on cell entry and T cell activation by RSV. Enzyme-linked immunosorbent assays were used to investigate the contribution of actin and clathrin on the release of interferon gamma. RESULTS: Cell entry, virus gene transcription and interferon gamma release are actin-dependent. Post-endocytic processes like the increased expression of major histocompatibility complex II on monocytes , T cell activation and the release of interferon gamma are clathrin-dependent. Finally, T cell receptor signaling affects T cell activation, whereas soluble interleukin 18 is dispensable. CONCLUSION: Analysis of cell entry and interferon gamma release after infection with RSV reveals the importance of actin- and clathrin-dependent signaling in human immune cells. Insights into the cellular biology of the human immune response against respiratory syncytial virus will provide a better understanding of disease pathogenesis and may prove useful in the development of preventive strategies.",2016 Mar 22,"['Jans, Jop', 'elMoussaoui, Hicham', 'de Groot, Ronald', 'de Jonge, Marien I.', 'Ferwerda, Gerben']",Virol J,,,True
90d553a545579b2e27d0899c558e004ff33cd0f4,PMC,Infection with and Carriage of Mycoplasma pneumoniae in Children,http://dx.doi.org/10.3389/fmicb.2016.00329,PMC4803743,27047456,CC BY,"“Atypical” pneumonia was described as a distinct and mild form of community-acquired pneumonia (CAP) already before Mycoplasma pneumoniae had been discovered and recognized as its cause. M. pneumoniae is detected in CAP patients most frequently among school-aged children from 5 to 15 years of age, with a decline after adolescence and tapering off in adulthood. Detection rates by polymerase chain reaction (PCR) or serology in children with CAP admitted to the hospital amount 4–39%. Although the infection is generally mild and self-limiting, patients of every age can develop severe or extrapulmonary disease. Recent studies indicate that high rates of healthy children carry M. pneumoniae in the upper respiratory tract and that current diagnostic PCR or serology cannot discriminate between M. pneumoniae infection and carriage. Further, symptoms and radiologic features are not specific for M. pneumoniae infection. Thus, patients may be unnecessarily treated with antimicrobials against M. pneumoniae. Macrolides are the first-line antibiotics for this entity in children younger than 8 years of age. Overall macrolides are extensively used worldwide, and this has led to the emergence of macrolide-resistant M. pneumoniae, which may be associated with severe clinical features and more extrapulmonary complications. This review focuses on the characteristics of M. pneumoniae infections in children, and exemplifies that simple clinical decision rules may help identifying children at high risk for CAP due to M. pneumoniae. This may aid physicians in prescribing appropriate first-line antibiotics, since current diagnostic tests for M. pneumoniae infection are not reliably predictive.",2016 Mar 23,"['Meyer Sauteur, Patrick M.', 'Unger, Wendy W. J.', 'Nadal, David', 'Berger, Christoph', 'Vink, Cornelis', 'van Rossum, Annemarie M. C.']",Front Microbiol,,,True
b562f1a519bc6a12df5e62930bdf4345cf0f7ce9,PMC,Utilization of the Emergency Department and Predicting Factors Associated With Its Use at the Saudi Ministry of Health General Hospitals,http://dx.doi.org/10.5539/gjhs.v8n1p90,PMC4803979,26234993,CC BY,"Overuse of emergency rooms (ER) is a public health problem. To investigate this issue, a cross-sectional survey was conducted at the ERs of King Abdul-Aziz Hospital, King Fahd Hospital, and Al-Thaghor Hospital in November 2013 with the aims of estimating emergency service utilization for non-urgent cases, identifying the predictors of ER utilization for non-urgent cases, and measuring patients’ knowledge of primary healthcare centers (PHCCs). Patients were interviewed using a structured questionnaire and the data were analyzed using the Statistical Package for the Social Sciences. We recruited 300 patients; males comprised 50.7% of the sample. A higher proportion of patients with non-urgent cases visited the ER three to four times a year (P=0.001). A higher proportion of patients without emergencies had not attempted to visit an outpatient clinic before the ER (P=0.003). Most patients without emergencies thought the ER was the first place to consult in case of illness. Most patients who visited the ER were single, < 15 years, and had lower incomes. Patients requested ER services for primary care-treatable conditions because of limited services and resources as well as limited working hours at PHCCs. Most patients (90.0%) were knowledgeable about PHCCs, with those of lower education being more knowledgeable. Patients reported long ER waiting times (≥ 3 hours), no organization (85.9%), and lack of medical staff. Overall, overuse of ER services is high at the Ministry of Health hospitals in Jeddah. The risk factors for ER overuse are age < 15 years, singlehood, and low incomes. Policy makers and health providers have a challenging task to control ER overuse. We recommend developing strategies to implement policies aimed at reducing non-urgent ER use as well as making healthcare services more available to the population.",2016 Jan 15,"['Dawoud, Sundus O.', 'Ahmad, Alaeddin Mohammad K.', 'Alsharqi, Omar Z.', 'Al-Raddadi, Rajaa M.']",Glob J Health Sci,,,True
925d90afe2cf113f16a0e28943763916963fdf24,PMC,Interpreting whole genome sequencing for investigating tuberculosis transmission: a systematic review,http://dx.doi.org/10.1186/s12916-016-0566-x,PMC4804562,27005433,CC BY,"BACKGROUND: Whole genome sequencing (WGS) is becoming an important part of epidemiological investigations of infectious diseases due to greater resolution and cost reductions compared to traditional typing approaches. Many public health and clinical teams will increasingly use WGS to investigate clusters of potential pathogen transmission, making it crucial to understand the benefits and assumptions of the analytical methods for investigating the data. We aimed to understand how different approaches affect inferences of transmission dynamics and outline limitations of the methods. METHODS: We comprehensively searched electronic databases for studies that presented methods used to interpret WGS data for investigating tuberculosis (TB) transmission. Two authors independently selected studies for inclusion and extracted data. Due to considerable methodological heterogeneity between studies, we present summary data with accompanying narrative synthesis rather than pooled analyses. RESULTS: Twenty-five studies met our inclusion criteria. Despite the range of interpretation tools, the usefulness of WGS data in understanding TB transmission often depends on the amount of genetic diversity in the setting. Where diversity is small, distinguishing re-infections from relapses may be impossible; interpretation may be aided by the use of epidemiological data, examining minor variants and deep sequencing. Conversely, when within-host diversity is large, due to genetic hitchhiking or co-infection of two dissimilar strains, it is critical to understand how it arose. Greater understanding of microevolution and mixed infection will enhance interpretation of WGS data. CONCLUSIONS: As sequencing studies have sampled more intensely and integrated multiple sources of information, the understanding of TB transmission and diversity has grown, but there is still much to be learnt about the origins of diversity that will affect inferences from these data. Public health teams and researchers should combine epidemiological, clinical and WGS data to strengthen investigations of transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-016-0566-x) contains supplementary material, which is available to authorized users.",2016 Mar 23,"['Hatherell, Hollie-Ann', 'Colijn, Caroline', 'Stagg, Helen R.', 'Jackson, Charlotte', 'Winter, Joanne R.', 'Abubakar, Ibrahim']",BMC Med,,,True
8dc3e3104105b1c360fdfe01de88e4f35d6977d0,PMC,A Highly Efficient and Simple Construction Strategy for Producing Recombinant Baculovirus Bombyx mori Nucleopolyhedrovirus,http://dx.doi.org/10.1371/journal.pone.0152140,PMC4805210,27008267,CC BY,"The silkworm baculovirus expression system is widely used to produce recombinant proteins. Several strategies for constructing recombinant viruses that contain foreign genes have been reported. Here, we developed a novel defective-rescue BmNPV Bacmid (reBmBac) expression system. A CopyControl origin of replication was introduced into the viral genome to facilitate its genetic manipulation in Escherichia coli and to ensure the preparation of large amounts of high quality reBmBac DNA as well as high quality recombinant baculoviruses. The ORF1629, cathepsin and chitinase genes were partially deleted or rendered defective to improve the efficiency of recombinant baculovirus generation and the expression of foreign genes. The system was validated by the successful expression of luciferase reporter gene and porcine interferon γ. This system can be used to produce batches of recombinant baculoviruses and target proteins rapidly and efficiently in silkworms.",2016 Mar 23,"['Liu, Xingjian', 'Wei, Yonglong', 'Li, Yinü', 'Li, Haoyang', 'Yang, Xin', 'Yi, Yongzhu', 'Zhang, Zhifang']",PLoS One,,,True
18073920e12ee20d939dee5116c586da8accfd82,PMC,A Novel Sample Processing Method for Rapid Detection of Tuberculosis in the Stool of Pediatric Patients Using the Xpert MTB/RIF Assay,http://dx.doi.org/10.1371/journal.pone.0151980,PMC4805262,27007974,CC BY,"BACKGROUND: Tuberculosis (TB) is difficult to diagnose in children using molecular tests, because children have difficulty providing respiratory samples. Stool could replace sputum for diagnostic TB testing if adequate sample processing techniques were available. METHODS: We developed a rapid method to process large volumes of stool for downstream testing by the Xpert MTB/RIF (Xpert) TB-detection assay. The method was tested and optimized on stool samples spiked with known numbers of M. tuberculosis colony forming units (CFU), and stools from M. tuberculosis-infected cynomolgus macaques (Macaca fascicularis). Performance was scored on number of positive Xpert tests, the cycle thresholds (Cts) of the Xpert sample-processing control (SPC), and the Cts of the M. tuberculosis-specific rpoB probes. The method was then validated on 20 confirmed TB cases and 20 controls in Durban, South Africa. RESULTS: The assay’s analytical limit of detection was 1,000 CFU/g of stool. As much as one gram of spiked stool could be tested without showing increased PCR inhibition. In analytical spiking experiments using human stool, 1g samples provided the best sensitivity compared to smaller amounts of sample. However, in Macaques with TB, 0.6g stool samples performed better than either 0.2g or 1.2g samples. Testing the stool of pediatric TB suspects and controls suggested an assay sensitivity of 85% (95% CI 0.6–0.9) and 84% (95% CI 0.6–0.96) for 0.6g and 1.2g stool samples, respectively, and a specificity of 100% (95% CI 0.77–1) and 94% (95% CI 0.7–0.99), respectively. CONCLUSION: This novel approach may permit simple and rapid detection of TB using pediatric stool samples.",2016 Mar 23,"['Banada, Padmapriya P.', 'Naidoo, Uvistra', 'Deshpande, Srinidhi', 'Karim, Farina', 'Flynn, JoAnne L.', 'O’Malley, Melanie', 'Jones, Martin', 'Nanassy, Oliver', 'Jeena, Prakash', 'Alland, David']",PLoS One,,,True
8e549a3356d7bd16111c4f682ae12a21ad4c5633,PMC,Wildlife Trade and Human Health in Lao PDR: An Assessment of the Zoonotic Disease Risk in Markets,http://dx.doi.org/10.1371/journal.pone.0150666,PMC4805265,27008628,CC BY,"Although the majority of emerging infectious diseases can be linked to wildlife sources, most pathogen spillover events to people could likely be avoided if transmission was better understood and practices adjusted to mitigate risk. Wildlife trade can facilitate zoonotic disease transmission and represents a threat to human health and economies in Asia, highlighted by the 2003 SARS coronavirus outbreak, where a Chinese wildlife market facilitated pathogen transmission. Additionally, wildlife trade poses a serious threat to biodiversity. Therefore, the combined impacts of Asian wildlife trade, sometimes termed bush meat trade, on public health and biodiversity need assessing. From 2010 to 2013, observational data were collected in Lao PDR from markets selling wildlife, including information on volume, form, species and price of wildlife; market biosafety and visitor origin. The potential for traded wildlife to host zoonotic diseases that pose a serious threat to human health was then evaluated at seven markets identified as having high volumes of trade. At the seven markets, during 21 observational surveys, 1,937 alive or fresh dead mammals (approximately 1,009 kg) were observed for sale, including mammals from 12 taxonomic families previously documented to be capable of hosting 36 zoonotic pathogens. In these seven markets, the combination of high wildlife volumes, high risk taxa for zoonoses and poor biosafety increases the potential for pathogen presence and transmission. To examine the potential conservation impact of trade in markets, we assessed the status of 33,752 animals observed during 375 visits to 93 markets, under the Lao PDR Wildlife and Aquatic Law. We observed 6,452 animals listed by Lao PDR as near extinct or threatened with extinction. The combined risks of wildlife trade in Lao PDR to human health and biodiversity highlight the need for a multi-sector approach to effectively protect public health, economic interests and biodiversity.",2016 Mar 23,"['Greatorex, Zoe F.', 'Olson, Sarah H.', 'Singhalath, Sinpakone', 'Silithammavong, Soubanh', 'Khammavong, Kongsy', 'Fine, Amanda E.', 'Weisman, Wendy', 'Douangngeun, Bounlom', 'Theppangna, Watthana', 'Keatts, Lucy', 'Gilbert, Martin', 'Karesh, William B.', 'Hansel, Troy', 'Zimicki, Susan', 'O’Rourke, Kathleen', 'Joly, Damien O.', 'Mazet, Jonna A. K.']",PLoS One,,,True
ce75acf2c22c37fdd88ecf5ed40c6713443fef47,PMC,"Cross-Reactivity of TCR Repertoire: Current Concepts, Challenges, and Implication for Allotransplantation",http://dx.doi.org/10.3389/fimmu.2016.00089,PMC4805583,27047489,CC BY,"Being able to track donor reactive T cells during the course of organ transplantation is a key to improve the graft survival, to prevent graft dysfunction, and to adapt the immunosuppressive regimen. The attempts of transplant immunologists have been for long hampered by the large size of the alloreactive T cell repertoire. Understanding how self-TCR can interact with allogeneic MHC is a key to critically appraise the different assays available to analyze the TCR Vβ repertoire usage. In this report, we will review conceptually and experimentally the process of cross-reactivity. We will then highlight what can be learned from allotransplantation, a situation of artificial cross-reactivity. Finally, the low- and high-resolution techniques to characterize the TCR Vβ repertoire usage in transplantation will be critically discussed.",2016 Mar 24,"['Degauque, Nicolas', 'Brouard, Sophie', 'Soulillou, Jean-Paul']",Front Immunol,,,True
d65ee92563369f173d038fe15c6f066c4f134385,PMC,The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles,http://dx.doi.org/10.1371/journal.ppat.1005501,PMC4806877,27010636,CC BY,"Arenaviruses cause severe diseases in humans but establish asymptomatic, lifelong infections in rodent reservoirs. Persistently-infected rodents harbor high levels of defective interfering (DI) particles, which are thought to be important for establishing persistence and mitigating virus-induced cytopathic effect. Little is known about what drives the production of DI particles. We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV) matrix protein nor a functional endosomal sorting complex transport (ESCRT) pathway is absolutely required for the generation of standard infectious virus particles. In contrast, DI particle release critically requires the PPXY late domain and is ESCRT-dependent. Additionally, the terminal tyrosine in the PPXY motif is reversibly phosphorylated and our findings indicate that this posttranslational modification may regulate DI particle formation. Thus we have uncovered a new role for the PPXY late domain and a possible mechanism for its regulation.",2016 Mar 24,"['Ziegler, Christopher M.', 'Eisenhauer, Philip', 'Bruce, Emily A.', 'Weir, Marion E.', 'King, Benjamin R.', 'Klaus, Joseph P.', 'Krementsov, Dimitry N.', 'Shirley, David J.', 'Ballif, Bryan A.', 'Botten, Jason']",PLoS Pathog,,,True
991aed7275084ce0661be421e281a8f47dcc8637,PMC,Selective Preference of Parallel DNA Triplexes Is Due to the Disruption of Hoogsteen Hydrogen Bonds Caused by the Severe Nonisostericity between the G*GC and T*AT Triplets,http://dx.doi.org/10.1371/journal.pone.0152102,PMC4807104,27010368,CC BY,"Implications of DNA, RNA and RNA.DNA hybrid triplexes in diverse biological functions, diseases and therapeutic applications call for a thorough understanding of their structure-function relationships. Despite exhaustive studies mechanistic rationale for the discriminatory preference of parallel DNA triplexes with G(*)GC & T(*)AT triplets still remains elusive. Here, we show that the highest nonisostericity between the G(*)GC & T(*)AT triplets imposes extensive stereochemical rearrangements contributing to context dependent triplex destabilisation through selective disruption of Hoogsteen scheme of hydrogen bonds. MD simulations of nineteen DNA triplexes with an assortment of sequence milieu reveal for the first time fresh insights into the nature and extent of destabilization from a single (non-overlapping), double (overlapping) and multiple pairs of nonisosteric base triplets (NIBTs). It is found that a solitary pair of NIBTs, feasible either at a G(*)GC/T(*)AT or T(*)AT/G(*)GC triplex junction, does not impinge significantly on triplex stability. But two overlapping pairs of NIBTs resulting from either a T(*)AT or a G(*)GC interruption disrupt Hoogsteen pair to a noncanonical mismatch destabilizing the triplex by ~10 to 14 kcal/mol, implying that their frequent incidence in multiples, especially, in short sequences could even hinder triplex formation. The results provide (i) an unambiguous and generalised mechanistic rationale for the discriminatory trait of parallel triplexes, including those studied experimentally (ii) clarity for the prevalence of antiparallel triplexes and (iii) comprehensive perspectives on the sequence dependent influence of nonisosteric base triplets useful in the rational design of TFO’s against potential triplex target sites.",2016 Mar 24,"['Goldsmith, Gunaseelan', 'Rathinavelan, Thenmalarchelvi', 'Yathindra, Narayanarao']",PLoS One,,,True
d3d29e7ae22aaff4cdc9769cbe97e57c438d5ef2,PMC,Chasing Ebola through the Endosomal Labyrinth,http://dx.doi.org/10.1128/mBio.00346-16,PMC4807365,27006455,CC BY,"During virus entry, the surface glycoprotein of Ebola virus (EBOV) undergoes a complex set of transformations within the endosomal network. Tools to study EBOV entry have been limited to static immunofluorescence or biochemical and functional analysis. In a recent article in mBio, Spence et al. reported a novel, live-cell-imaging method that tracks this transformational journey of EBOV in real time [J. S. Spence, T. B. Krause, E. Mittler, R. K. Jangra, and K. Chandran, mBio 7(1):e01857-15, 2016, http://dx.doi.org/10.1128/mBio.01857-15]. The assay validates known mechanisms of EBOV entry and sheds light on some novel intricacies. Direct evidence supports the hypothesis that fusion is a rare event that starts in maturing early endosomes, is completed in late endosomes, and occurs entirely in Niemann-Pick C1 (NPC1)-positive (NPC1(+)) compartments. The study demonstrated that lipid mixing and productive fusion are temporally decoupled, with different energetic barriers and a protease-dependent step between the two events. Analysis of the mechanism of action of an important class of EBOV neutralizing antibodies, such as KZ52 and ZMapp, provides direct evidence that these antibodies act by inhibiting the membrane fusion.",2016 Mar 22,"Aman, M. Javad",mBio,,,True
8e014e2133b319d93ba7e9341ffe33bab3f9e265,PMC,A HLA-A2-restricted CTL epitope induces anti-tumor effects against human lung cancer in mouse xenograft model,,PMC4808025,26621839,CC BY,"Cancer immunotherapy is attractive for antigen-specific T cell-mediated anti-tumor therapy, especially in induction of cytotoxic T lymphocytes. In this report, we evaluated human CTL epitope-induced anti-tumor effects in human lung cancer xenograft models. The tumor associated antigen L6 (TAL6) is highly expressed in human lung cancer cell lines and tumor specimens as compared to normal lung tissues. TAL6 derived peptides strongly inhibited tumor growth, cancer metastasis and prolonged survival time in HLA-A2 transgenic mice immunized with a formulation of T-helper (Th) peptide, synthetic CpG ODN, and adjuvant Montanide ISA-51 (ISA-51). Adoptive transfer of peptide-induced CTL cells from HLA-A2 transgenic mice into human tumor xenograft SCID mice significantly inhibited tumor growth. Furthermore, combination of CTL-peptide immunotherapy and gemcitabine additively improved the therapeutic effects. This pre-clinical evaluation model provides a useful platform to develop efficient immunotherapeutic drugs to treat lung cancer and demonstrates a promising strategy with benefit of antitumor immune responses worthy of further development in clinical trials.",2015 Nov 26,"['Sher, Yuh-Pyng', 'Lin, Su-I', 'Chen, I-Hua', 'Liu, Hsin-Yu', 'Lin, Chen-Yuan', 'Chiang, I-Ping', 'Roffler, Steve', 'Chen, Hsin-Wei', 'Liu, Shih-Jen']",Oncotarget,,,True
53b682ee21a1000891bc2cc0363feea27dce7398,PMC,A HLA-A2-restricted CTL epitope induces anti-tumor effects against human lung cancer in mouse xenograft model,,PMC4808025,26621839,CC BY,"Cancer immunotherapy is attractive for antigen-specific T cell-mediated anti-tumor therapy, especially in induction of cytotoxic T lymphocytes. In this report, we evaluated human CTL epitope-induced anti-tumor effects in human lung cancer xenograft models. The tumor associated antigen L6 (TAL6) is highly expressed in human lung cancer cell lines and tumor specimens as compared to normal lung tissues. TAL6 derived peptides strongly inhibited tumor growth, cancer metastasis and prolonged survival time in HLA-A2 transgenic mice immunized with a formulation of T-helper (Th) peptide, synthetic CpG ODN, and adjuvant Montanide ISA-51 (ISA-51). Adoptive transfer of peptide-induced CTL cells from HLA-A2 transgenic mice into human tumor xenograft SCID mice significantly inhibited tumor growth. Furthermore, combination of CTL-peptide immunotherapy and gemcitabine additively improved the therapeutic effects. This pre-clinical evaluation model provides a useful platform to develop efficient immunotherapeutic drugs to treat lung cancer and demonstrates a promising strategy with benefit of antitumor immune responses worthy of further development in clinical trials.",2015 Nov 26,"['Sher, Yuh-Pyng', 'Lin, Su-I', 'Chen, I-Hua', 'Liu, Hsin-Yu', 'Lin, Chen-Yuan', 'Chiang, I-Ping', 'Roffler, Steve', 'Chen, Hsin-Wei', 'Liu, Shih-Jen']",Oncotarget,,,False
786da349a33148e24e09edd6378da80ea2f40e07,PMC,Common variations in TERT-CLPTM1L locus are reproducibly associated with the risk of nasopharyngeal carcinoma in Chinese populations,,PMC4808031,26621837,CC BY,"Associations between single nucleotide polymorphisms (SNPs) at 5p15 (TERT-CLPTM1L) and multiple cancer types have been reported. We examined whether polymorphisms in the TERT-CLPTM1L locus were related to the risk of developing nasopharyngeal carcinoma (NPC) among Chinese populations. In the first stage, 26 tag SNPs were genotyped in a Guangxi population (855 patients and 1036 controls). In the second stage, the SNPs, which showed significant association, were further genotyped in a Guangdong population (997 patients and 972 controls). Functional analyses were conducted to verify the biological relevance of the associated polymorphism. In the 1st stage, four SNPs (rs2736098, rs2735845, rs402710, and rs401681) were significantly associated with the risk of developing NPC. After the 2nd stage validation, rs2735845 and rs401681 were independently associated with the risk of developing NPC in the additive model (rs2735845, OR = 1.19, 95% CI = 1.04–1.37, P = 0.011; rs401681, OR = 0.85, 95% CI = 0.74–0.99, P = 0.034). Furthermore, we observed higher CLPTM1L messenger RNA levels in fetal mesenchymal stem cells from the rs2735845 G allele carriers compared with that from non-carriers. In addition, using an immunohistochemistry assay, we observed higher TERT and CLPTM1L levels in NPC tissues compared with that in non-cancerous nasopharyngeal tissues. Our findings suggest that polymorphisms in the TERT-CLPTM1L locus may play a role in mediating the susceptibility to NPC in Chinese populations.",2015 Nov 26,"['Zhang, Yang', 'Zhang, Xiaoai', 'Zhang, Hongxing', 'Zhai, Yun', 'Wang, Zhifu', 'Li, Peiyao', 'Yu, Lixia', 'Xia, Xia', 'Zhang, Ying', 'Zeng, Yixin', 'He, Fuchu', 'Zhou, Gangqiao']",Oncotarget,,,True
2810296105b6ae2ca21d299d27f83c6d1b071f28,PMC,Common variations in TERT-CLPTM1L locus are reproducibly associated with the risk of nasopharyngeal carcinoma in Chinese populations,,PMC4808031,26621837,CC BY,"Associations between single nucleotide polymorphisms (SNPs) at 5p15 (TERT-CLPTM1L) and multiple cancer types have been reported. We examined whether polymorphisms in the TERT-CLPTM1L locus were related to the risk of developing nasopharyngeal carcinoma (NPC) among Chinese populations. In the first stage, 26 tag SNPs were genotyped in a Guangxi population (855 patients and 1036 controls). In the second stage, the SNPs, which showed significant association, were further genotyped in a Guangdong population (997 patients and 972 controls). Functional analyses were conducted to verify the biological relevance of the associated polymorphism. In the 1st stage, four SNPs (rs2736098, rs2735845, rs402710, and rs401681) were significantly associated with the risk of developing NPC. After the 2nd stage validation, rs2735845 and rs401681 were independently associated with the risk of developing NPC in the additive model (rs2735845, OR = 1.19, 95% CI = 1.04–1.37, P = 0.011; rs401681, OR = 0.85, 95% CI = 0.74–0.99, P = 0.034). Furthermore, we observed higher CLPTM1L messenger RNA levels in fetal mesenchymal stem cells from the rs2735845 G allele carriers compared with that from non-carriers. In addition, using an immunohistochemistry assay, we observed higher TERT and CLPTM1L levels in NPC tissues compared with that in non-cancerous nasopharyngeal tissues. Our findings suggest that polymorphisms in the TERT-CLPTM1L locus may play a role in mediating the susceptibility to NPC in Chinese populations.",2015 Nov 26,"['Zhang, Yang', 'Zhang, Xiaoai', 'Zhang, Hongxing', 'Zhai, Yun', 'Wang, Zhifu', 'Li, Peiyao', 'Yu, Lixia', 'Xia, Xia', 'Zhang, Ying', 'Zeng, Yixin', 'He, Fuchu', 'Zhou, Gangqiao']",Oncotarget,,,True
e9dfffbed92e23efc7241bae7623b4584f50b69e,PMC,Global Strategies for the Prevention and Control of Infectious Diseases and Non-Communicable Diseases,http://dx.doi.org/10.2188/jea.JE20160010,PMC4808683,26947953,CC BY,"This article on global health reviews the environment surrounding health strategies and plans, as well as lessons learned from the first 15 years of the 21st century, followed by a discussion on the quest for a new paradigm for disease control efforts and challenges and opportunities for Japan.",2016 Apr 5,"Nakatani, Hiroki",J Epidemiol,,,True
ca52af941437873b4122bb2e26d7e3fab81cd73f,PMC,Activation of the DNA Damage Response by RNA Viruses,http://dx.doi.org/10.3390/biom6010002,PMC4808796,26751489,CC BY,"RNA viruses are a genetically diverse group of pathogens that are responsible for some of the most prevalent and lethal human diseases. Numerous viruses introduce DNA damage and genetic instability in host cells during their lifecycles and some species also manipulate components of the DNA damage response (DDR), a complex and sophisticated series of cellular pathways that have evolved to detect and repair DNA lesions. Activation and manipulation of the DDR by DNA viruses has been extensively studied. It is apparent, however, that many RNA viruses can also induce significant DNA damage, even in cases where viral replication takes place exclusively in the cytoplasm. DNA damage can contribute to the pathogenesis of RNA viruses through the triggering of apoptosis, stimulation of inflammatory immune responses and the introduction of deleterious mutations that can increase the risk of tumorigenesis. In addition, activation of DDR pathways can contribute positively to replication of viral RNA genomes. Elucidation of the interactions between RNA viruses and the DDR has provided important insights into modulation of host cell functions by these pathogens. This review summarises the current literature regarding activation and manipulation of the DDR by several medically important RNA viruses.",2016 Jan 6,"['Ryan, Ellis L.', 'Hollingworth, Robert', 'Grand, Roger J.']",Biomolecules,,,True
96464179873570564cc07be6219abb043caad44a,PMC,Modeling Heterogeneity in Direct Infectious Disease Transmission in a Compartmental Model,http://dx.doi.org/10.3390/ijerph13030253,PMC4808916,26927140,CC BY,"Mathematical models have been used to understand the transmission dynamics of infectious diseases and to assess the impact of intervention strategies. Traditional mathematical models usually assume a homogeneous mixing in the population, which is rarely the case in reality. Here, we construct a new transmission function by using as the probability density function a negative binomial distribution, and we develop a compartmental model using it to model the heterogeneity of contact rates in the population. We explore the transmission dynamics of the developed model using numerical simulations with different parameter settings, which characterize different levels of heterogeneity. The results show that when the reproductive number, [Formula: see text] , is larger than one, a low level of heterogeneity results in dynamics similar to those predicted by the homogeneous mixing model. As the level of heterogeneity increases, the dynamics become more different. As a test case, we calibrated the model with the case incidence data for severe acute respiratory syndrome (SARS) in Beijing in 2003, and the estimated parameters demonstrated the effectiveness of the control measures taken during that period.",2016 Mar 24,"['Kong, Lingcai', 'Wang, Jinfeng', 'Han, Weiguo', 'Cao, Zhidong']",Int J Environ Res Public Health,,,True
5153d1fa1f68741534152792b0b6b15e2dcf4490,PMC,"Erratum: Li, M., et al. Middle East Respiratory Syndrome and Medical Students: Letter from China. Int. J. Environ. Res. Public Health 2015, 12, 13289–13294",http://dx.doi.org/10.3390/ijerph13030335,PMC4808998,26999182,CC BY,,2016 Mar 18,,Int J Environ Res Public Health,,,False
b8ee195be637c05754e714310c9d0d5ba715d683,PMC,"Overview of Infectious Disease Surveillance System in Japan, 1999-2005",http://dx.doi.org/10.2188/jea.17.S3,PMC4809251,18239339,CC BY,"BACKGROUND: In 1999 the Communicable Disease Prevention Law of Japan was completely revised into the ""New"" Infectious Disease Control Law, which reiterated the importance of surveillance and information dissemination and re-organized the surveillance system. This paper is an attempt to illustrate the potential impact of the new surveillance system through a description of the existing surveillance system and data before and after the revision. METHODS: After a historical review of surveillance system in Japan, the current surveillance system is described. Data sets of actual case numbers reported and incidence rate per 1,000,000 population are compared before and after the revision. RESULTS: Comparison of the data between the 2 periods revealed that most of the diseases have had declining trends after the new law was enacted with several exceptions. However, although no major break in continuity is observed in seriously perceived disease, in milder diseases there are striking gaps between the numbers reported in the mandatory and sentinel reporting framework. Sentinel reporting framework maintained the continuity of data without major gaps. CONCLUSIONS: From this perspective, the new surveillance system with two different frameworks of mandatory reporting for severe diseases and sentinel reporting for milder diseases seems to be working well. But continuous efforts should be made for evaluation and improvement of surveillance system and risk communication through the research on data analysis and effective communication method.",2008 Jan 30,"['Taniguchi, Kiyosu', 'Hashimoto, Shuji', 'Kawado, Miyuki', 'Murakami, Yoshitaka', 'Izumida, Michiko', 'Ohta, Akiko', 'Tada, Yuki', 'Shigematsu, Mika', 'Yasui, Yoshinori', 'Nagai, Masaki']",J Epidemiol,,,True
5df6b1ce03de2b78801de3d8e20a50b3563a2cf4,PMC,Viral Interactions with PDZ Domain-Containing Proteins—An Oncogenic Trait?,http://dx.doi.org/10.3390/pathogens5010008,PMC4810129,26797638,CC BY,"Many of the human viruses with oncogenic capabilities, either in their natural host or in experimental systems (hepatitis B and C, human T cell leukaemia virus type 1, Kaposi sarcoma herpesvirus, human immunodeficiency virus, high-risk human papillomaviruses and adenovirus type 9), encode in their limited genome the ability to target cellular proteins containing PSD95/ DLG/ZO-1 (PDZ) interaction modules. In many cases (but not always), the viruses have evolved to bind the PDZ domains using the same short linear peptide motifs found in host protein-PDZ interactions, and in some cases regulate the interactions in a similar fashion by phosphorylation. What is striking is that the diverse viruses target a common subset of PDZ proteins that are intimately involved in controlling cell polarity and the structure and function of intercellular junctions, including tight junctions. Cell polarity is fundamental to the control of cell proliferation and cell survival and disruption of polarity and the signal transduction pathways involved is a key event in tumourigenesis. This review focuses on the oncogenic viruses and the role of targeting PDZ proteins in the virus life cycle and the contribution of virus-PDZ protein interactions to virus-mediated oncogenesis. We highlight how many of the viral associations with PDZ proteins lead to deregulation of PI3K/AKT signalling, benefitting virus replication but as a consequence also contributing to oncogenesis.",2016 Jan 18,"['James, Claire D.', 'Roberts, Sally']",Pathogens,,,True
021144f6c1945b9bff9ea9e4b04b24dcf53330b4,PMC,Identification and Comparison of Receptor Binding Characteristics of the Spike Protein of Two Porcine Epidemic Diarrhea Virus Strains,http://dx.doi.org/10.3390/v8030055,PMC4810246,26907329,CC BY,"Porcine epidemic diarrhea virus (PEDV), a member of Alphacoronavirus, has caused huge economic losses for the global pork industry recently. The spike (S) protein mediates PEDV entry into host cells. Herein, we investigated the interactions between the S protein and its receptor porcine aminopeptidase N (pAPN) or co-receptor sugars. The C-terminal domain (CTD) of the S1 domain is bound to pAPN. The prototype strain demonstrated similar receptor-binding activity compared with the variant field isolate. Three loops at the tips of the β-barrel domains did not play crucial roles in the PEDV S-pAPN association, indicating that PEDV conforms to a different receptor recognition model compared with transmissible gastroenteritis virus (TGEV), porcine respiratory CoV (PRCV), and human coronavirus NL63 (HCoV-NL63). The N-terminal domain (NTD) of the PEDV S1 domain could bind sugar, a possible co-receptor for PEDV. The prototype strain exhibited weaker sugar-binding activity compared with the variant field isolate. Strategies targeting the receptor binding domain (RBD) may be helpful for developing vaccines or antiviral drugs for PEDV. Understanding the differences in receptor binding between the prototype and the variant strains may provide insight into PEDV pathogenesis.",2016 Feb 23,"['Deng, Feng', 'Ye, Gang', 'Liu, Qianqian', 'Navid, Muhammad Tariq', 'Zhong, Xiaoli', 'Li, Youwen', 'Wan, Chunyun', 'Xiao, Shaobo', 'He, Qigai', 'Fu, Zhen F.', 'Peng, Guiqing']",Viruses,,,True
4b81c74ca2592fb4e3e81f9013a98fe890cb42e4,PMC,Identification and Comparison of Receptor Binding Characteristics of the Spike Protein of Two Porcine Epidemic Diarrhea Virus Strains,http://dx.doi.org/10.3390/v8030055,PMC4810246,26907329,CC BY,"Porcine epidemic diarrhea virus (PEDV), a member of Alphacoronavirus, has caused huge economic losses for the global pork industry recently. The spike (S) protein mediates PEDV entry into host cells. Herein, we investigated the interactions between the S protein and its receptor porcine aminopeptidase N (pAPN) or co-receptor sugars. The C-terminal domain (CTD) of the S1 domain is bound to pAPN. The prototype strain demonstrated similar receptor-binding activity compared with the variant field isolate. Three loops at the tips of the β-barrel domains did not play crucial roles in the PEDV S-pAPN association, indicating that PEDV conforms to a different receptor recognition model compared with transmissible gastroenteritis virus (TGEV), porcine respiratory CoV (PRCV), and human coronavirus NL63 (HCoV-NL63). The N-terminal domain (NTD) of the PEDV S1 domain could bind sugar, a possible co-receptor for PEDV. The prototype strain exhibited weaker sugar-binding activity compared with the variant field isolate. Strategies targeting the receptor binding domain (RBD) may be helpful for developing vaccines or antiviral drugs for PEDV. Understanding the differences in receptor binding between the prototype and the variant strains may provide insight into PEDV pathogenesis.",2016 Feb 23,"['Deng, Feng', 'Ye, Gang', 'Liu, Qianqian', 'Navid, Muhammad Tariq', 'Zhong, Xiaoli', 'Li, Youwen', 'Wan, Chunyun', 'Xiao, Shaobo', 'He, Qigai', 'Fu, Zhen F.', 'Peng, Guiqing']",Viruses,,,False
685efeb0ad4c214b8295dc4f723c3269464772d8,PMC,Isolation of a Novel Fusogenic Orthoreovirus from Eucampsipoda africana Bat Flies in South Africa,http://dx.doi.org/10.3390/v8030065,PMC4810255,27011199,CC BY,"We report on the isolation of a novel fusogenic orthoreovirus from bat flies (Eucampsipoda africana) associated with Egyptian fruit bats (Rousettus aegyptiacus) collected in South Africa. Complete sequences of the ten dsRNA genome segments of the virus, tentatively named Mahlapitsi virus (MAHLV), were determined. Phylogenetic analysis places this virus into a distinct clade with Baboon orthoreovirus, Bush viper reovirus and the bat-associated Broome virus. All genome segments of MAHLV contain a 5' terminal sequence (5'-GGUCA) that is unique to all currently described viruses of the genus. The smallest genome segment is bicistronic encoding for a 14 kDa protein similar to p14 membrane fusion protein of Bush viper reovirus and an 18 kDa protein similar to p16 non-structural protein of Baboon orthoreovirus. This is the first report on isolation of an orthoreovirus from an arthropod host associated with bats, and phylogenetic and sequence data suggests that MAHLV constitutes a new species within the Orthoreovirus genus.",2016 Feb 29,"['Jansen van Vuren, Petrus', 'Wiley, Michael', 'Palacios, Gustavo', 'Storm, Nadia', 'McCulloch, Stewart', 'Markotter, Wanda', 'Birkhead, Monica', 'Kemp, Alan', 'Paweska, Janusz T.']",Viruses,,,True
70948646d2777b7a433c7558b5c3488bdb77e526,PMC,Roles of the Picornaviral 3C Proteinase in the Viral Life Cycle and Host Cells,http://dx.doi.org/10.3390/v8030082,PMC4810272,26999188,CC BY,"The Picornaviridae family comprises a large group of non-enveloped viruses that have a major impact on human and veterinary health. The viral genome contains one open reading frame encoding a single polyprotein that can be processed by viral proteinases. The crucial 3C proteinases (3C(pro)s) of picornaviruses share similar spatial structures and it is becoming apparent that 3C(pro) plays a significant role in the viral life cycle and virus host interaction. Importantly, the proteinase and RNA-binding activity of 3C(pro) are involved in viral polyprotein processing and the initiation of viral RNA synthesis. In addition, 3C(pro) can induce the cleavage of certain cellular factors required for transcription, translation and nucleocytoplasmic trafficking to modulate cell physiology for viral replication. Due to interactions between 3C(pro) and these essential factors, 3C(pro) is also involved in viral pathogenesis to support efficient infection. Furthermore, based on the structural conservation, the development of irreversible inhibitors and discovery of non-covalent inhibitors for 3C(pro) are ongoing and a better understanding of the roles played by 3C(pro) may provide insights into the development of potential antiviral treatments. In this review, the current knowledge regarding the structural features, multiple functions in the viral life cycle, pathogen host interaction, and development of antiviral compounds for 3C(pro) is summarized.",2016 Mar 17,"['Sun, Di', 'Chen, Shun', 'Cheng, Anchun', 'Wang, Mingshu']",Viruses,,,True
6da13d90743ba52bded6ed06e214541ba19d5078,PMC,Discovery of Novel Alphacoronaviruses in European Rodents and Shrews,http://dx.doi.org/10.3390/v8030084,PMC4810274,27102167,CC BY,"Eight hundred and thirteen European rodents and shrews encompassing seven different species were screened for alphacoronaviruses using PCR detection. Novel alphacoronaviruses were detected in the species Rattus norvegicus, Microtus agrestis, Sorex araneus and Myodes glareolus. These, together with the recently described Lucheng virus found in China, form a distinct rodent/shrew-specific clade within the coronavirus phylogeny. Across a highly conserved region of the viral polymerase gene, the new members of this clade were up to 22% dissimilar at the nucleotide level to the previously described Lucheng virus. As such they might represent distinct species of alphacoronaviruses. These data greatly extend our knowledge of wildlife reservoirs of alphacoronaviruses.",2016 Mar 18,"['Tsoleridis, Theocharis', 'Onianwa, Okechukwu', 'Horncastle, Emma', 'Dayman, Emma', 'Zhu, Miaoran', 'Danjittrong, Taechasit', 'Wachtl, Marta', 'Behnke, Jerzy M.', 'Chapman, Sarah', 'Strong, Victoria', 'Dobbs, Phillipa', 'Ball, Jonathan K.', 'Tarlinton, Rachael E.', 'McClure, C. Patrick']",Viruses,,,True
e01d6fcf286c7231445ac9db61237ac71ca26fec,PMC,"Porcine Sapelovirus Uses α2,3-Linked Sialic Acid on GD1a Ganglioside as a Receptor",http://dx.doi.org/10.1128/JVI.02449-15,PMC4810533,26865725,CC BY,"The receptor(s) for porcine sapelovirus (PSV), which causes diarrhea, pneumonia, polioencephalomyelitis, and reproductive disorders in pigs, remains largely unknown. Given the precedent for other picornaviruses which use terminal sialic acids (SAs) as receptors, we examined the role of SAs in PSV binding and infection. Using a variety of approaches, including treating cells with a carbohydrate-destroying chemical (NaIO(4)), mono- or oligosaccharides (N-acetylneuraminic acid, galactose, and 6′-sialyllactose), linkage-specific sialidases (neuraminidase and sialidase S), lectins (Maakia amurensis lectin and Sambucus nigra lectin), proteases (trypsin and chymotrypsin), and glucosylceramide synthase inhibitors (dl-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol and phospholipase C), we demonstrated that PSV could recognize α2,3-linked SA on glycolipids as a receptor. On the other hand, PSVs had no binding affinity for synthetic histo-blood group antigens (HBGAs), suggesting that PSVs could not use HBGAs as receptors. Depletion of cell surface glycolipids followed by reconstitution studies indicated that GD1a ganglioside, but not other gangliosides, could restore PSV binding and infection, further confirming α2,3-linked SA on GD1a as a PSV receptor. Our results could provide significant information on the understanding of the life cycle of sapelovirus and other picornaviruses. For the broader community in the area of pathogens and pathogenesis, these findings and insights could contribute to the development of affordable, useful, and efficient drugs for anti-sapelovirus therapy. IMPORTANCE The porcine sapelovirus (PSV) is known to cause enteritis, pneumonia, polioencephalomyelitis, and reproductive disorders in pigs. However, the receptor(s) that the PSV utilizes to enter host cells remains largely unknown. Using a variety of approaches, we showed that α2,3-linked terminal sialic acid (SA) on the cell surface GD1a ganglioside could be used for PSV binding and infection as a receptor. On the other hand, histo-blood group antigens also present in the cell surface carbohydrates could not be utilized as PSV receptors for binding and infection. These findings should contribute to the understanding of the sapelovirus life cycle and to the development of affordable, useful and efficient drugs for anti-sapelovirus therapy.",2016 Mar 28,"['Kim, Deok-Song', 'Son, Kyu-Yeol', 'Koo, Kyung-Min', 'Kim, Ji-Yun', 'Alfajaro, Mia Madel', 'Park, Jun-Gyu', 'Hosmillo, Myra', 'Soliman, Mahmoud', 'Baek, Yeong-Bin', 'Cho, Eun-Hyo', 'Lee, Ju-Hwan', 'Kang, Mun-Il', 'Goodfellow, Ian', 'Cho, Kyoung-Oh']",J Virol,,,True
281303193aa29253bb0b00328b48e892d0cf4f85,PMC,Low-Fidelity Polymerases of Alphaviruses Recombine at Higher Rates To Overproduce Defective Interfering Particles,http://dx.doi.org/10.1128/JVI.02921-15,PMC4810721,26676773,CC BY,"Low-fidelity RNA-dependent RNA polymerases for many RNA virus mutators have been shown to confer attenuated phenotypes, presumably due to increased mutation rates. Additionally, for many RNA viruses, replication to high titers results in the production of defective interfering particles (DIs) that also attenuate infection. We hypothesized that fidelity, recombination, and DI production are tightly linked. We show that a Sindbis virus mutator replicating at a high multiplicity of infection manifests an earlier and greater accumulation of DIs than its wild-type counterpart. The isolated DIs interfere with the replication of full-length virus in a dose-dependent manner. Importantly, the ability of the mutator virus to overproduce DIs could be linked to an increased recombination frequency. These data confirm that RNA-dependent RNA polymerase fidelity and recombination are inversely correlated for this mutator. Our findings suggest that defective interference resulting from higher recombination rates may be more detrimental to RNA virus mutators than the increase in mutational burden. IMPORTANCE Replication, adaptation, and evolution of RNA viruses rely in large part on their low-fidelity RNA-dependent RNA polymerase. Viruses artificially modified in their polymerases to decrease fidelity (mutator viruses) are attenuated in vivo, demonstrating the important role of fidelity in viral fitness. However, attenuation was attributed solely to the modification of the viral mutation rate and the accumulation of detrimental point mutations. In this work, we described an additional phenotype of mutator viruses: an increased recombination rate leading to defective interfering particle (DI) overproduction. Because DIs are known for their inhibitory effect on viral replication, our work suggests that fidelity variants may be attenuated in vivo via several mechanisms. This has important implications in the development of fidelity variants as live attenuated vaccine strains.",2016 Feb 11,"['Poirier, Enzo Z.', 'Mounce, Bryan C.', 'Rozen-Gagnon, Kathryn', 'Hooikaas, Peter Jan', 'Stapleford, Kenneth A.', 'Moratorio, Gonzalo', 'Vignuzzi, Marco']",J Virol,,,True
2d85ecf540b138ba2c5dd735bcf986c58ede052e,PMC,"Ethanol Extract of Sanguisorbae Radix Inhibits Mast Cell Degranulation and Suppresses 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions",http://dx.doi.org/10.1155/2016/2947390,PMC4811174,27065570,CC BY,"Sanguisorbae Radix (SR) is well known as herbal medicine named “Zi-Yu” in Korea, which is the dried roots of Sanguisorba officinalis L. (Rosacease). We investigated the underlying mechanism on the inhibition of atopic dermatitis (AD) of an ethanol extract of SR (ESR) using 2,4-dinitrochlorobenzene- (DNCB-) induced AD mice model. Oral administration of ESR significantly suppressed DNCB-induced AD-like symptoms such as scratching behavior, ear thickness, epidermal thickness, and IgE levels. To investigate the effects of ESR treatment on degranulation of IgE/Ag-activated mouse bone marrow-derived mast cells (BMMCs), we measured the release of β-hexosaminidase (β-HEX, degranulation marker). ESR decreased the infiltration of eosinophils and mast cells into the AD skin lesions. Furthermore, ESR significantly inhibited degranulation of IgE/Ag-activated BMMCs. We have demonstrated that ESR decreased AD symptoms in mice and inhibits degranulation of IgE/Ag-activated mast cells. Our study suggests that ESR may serve as a potential therapeutic candidate for the treatment of AD symptoms.",2016 Mar 15,"['Yang, Ju-Hye', 'Yoo, Jae-Myung', 'Cho, Won-Kyung', 'Ma, Jin Yeul']",Mediators Inflamm,,,True
398cbb196acb9f8ee91a22edcca3b32c044878b8,PMC,Evolutionary reversion of live viral vaccines: Can genetic engineering subdue it?,http://dx.doi.org/10.1093/ve/vev005,PMC4811365,27034780,CC BY,"Attenuated, live viral vaccines have been extraordinarily successful in protecting against many diseases. The main drawbacks in their development and use have been reliance on an unpredictable method of attenuation and the potential for evolutionary reversion to high virulence. Methods of genetic engineering now provide many safer alternatives to live vaccines, so if live vaccines are to compete with these alternatives in the future, they must either have superior immunogenicity or they must be able to overcome these former disadvantages. Several live vaccine designs that were historically inaccessible are now feasible because of advances in genome synthesis. Some of those methods are addressed here, with an emphasis on whether they enable predictable levels of attenuation and whether they are stable against evolutionary reversion. These new designs overcome many of the former drawbacks and position live vaccines to be competitive with alternatives. Not only do new methods appear to retard evolutionary reversion enough to prevent vaccine-derived epidemics, but it may even be possible to permanently attenuate live vaccines that are transmissible but cannot evolve to higher virulence under prolonged adaptation.",2015 Jul 31,"Bull, J. J.",Virus Evol,,,True
434ab543a48b7fb395d181ffb947814bd1b506c4,PMC,The Roles of Histidines and Charged Residues as Potential Triggers of a Conformational Change in the Fusion Loop of Ebola Virus Glycoprotein,http://dx.doi.org/10.1371/journal.pone.0152527,PMC4811418,27023721,CC BY,"Ebola virus (EBOV) enters cells from late endosomes/lysosomes under mildly acidic conditions. Entry by fusion with the endosomal membrane requires the fusion loop (FL, residues 507–560) of the EBOV surface glycoprotein to undergo a pH-dependent conformational change. To find the pH trigger for this reaction we mutated multiple conserved histidines and charged and uncharged hydrophilic residues in the FL and measured their activity by liposome fusion and cell entry of virus-like particles. The FL location in the membrane was assessed by NMR using soluble and lipid-bound paramagnetic relaxation agents. While we could not identify a single residue to be alone responsible for pH triggering, we propose that a distributed pH effect over multiple residues induces the conformational change that enhances membrane insertion and triggers the fusion activity of the EBOV FL.",2016 Mar 29,"['Lee, Jinwoo', 'Gregory, Sonia M.', 'Nelson, Elizabeth A.', 'White, Judith M.', 'Tamm, Lukas K.']",PLoS One,,,True
c3e58660ecf2f667fb13b113859dba3a87ef36fe,PMC,Translation of Korean Medicine Use to ICD-Codes Using National Health Insurance Service-National Sample Cohort,http://dx.doi.org/10.1155/2016/8160838,PMC4812360,27069494,CC BY,"Background. Korean medicine was incorporated into the Korean Classification of Diseases (KCD) 6 through the development of U codes (U20–U99). Studies of the burden of disease have used summary measures such as disability-adjusted life years. Although Korean medicine is included in the official health care system, studies of the burden of disease that include Korean medicine are lacking. Methods. A data-based approach was used with National Health Insurance Service-National Sample Cohort data for the year 2012. U code diagnoses for patients covered by National Health Insurance were collected. Using the main disease and subdisease codes, the proportion of U codes was redistributed into the related KCD 6 codes and visualized. U code and KCD code relevance was appraised prior to the analysis by consultation with medical professionals and from the beta draft version of the International Classification of Diseases-11 traditional medicine chapter. Results. This approach enabled redistribution of U codes into KCD 6 codes. Musculoskeletal diseases had the greatest increase in the burden of disease through this approach. Conclusion. This study provides a possible method of incorporating Korean medicine into burden of disease analyses through a data-based approach. Further studies should analyze potential yearly differences.",2016 Mar 16,"['Lee, Ye-Seul', 'Lee, Ye-Rin', 'Chae, Younbyoung', 'Park, So-Youn', 'Oh, In-Hwan', 'Jang, Bo-Hyoung']",Evid Based Complement Alternat Med,,,True
eb0a05f4e7d9d276e308e8f6e80617962b07f9cb,PMC,"Molecular Selection, Modification and Development of Therapeutic Oligonucleotide Aptamers",http://dx.doi.org/10.3390/ijms17030358,PMC4813219,26978355,CC BY,"Monoclonal antibodies are the dominant agents used in inhibition of biological target molecules for disease therapeutics, but there are concerns of immunogenicity, production, cost and stability. Oligonucleotide aptamers have comparable affinity and specificity to targets with monoclonal antibodies whilst they have minimal immunogenicity, high production, low cost and high stability, thus are promising inhibitors to rival antibodies for disease therapy. In this review, we will compare the detailed advantages and disadvantages of antibodies and aptamers in therapeutic applications and summarize recent progress in aptamer selection and modification approaches. We will present therapeutic oligonucleotide aptamers in preclinical studies for skeletal diseases and further discuss oligonucleotide aptamers in different stages of clinical evaluation for various disease therapies including macular degeneration, cancer, inflammation and coagulation to highlight the bright commercial future and potential challenges of therapeutic oligonucleotide aptamers.",2016 Mar 11,"['Yu, Yuanyuan', 'Liang, Chao', 'Lv, Quanxia', 'Li, Defang', 'Xu, Xuegong', 'Liu, Baoqin', 'Lu, Aiping', 'Zhang, Ge']",Int J Mol Sci,,,True
5f3f613be264f8b10318dfe8e92777fe7a95848e,PMC,Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in Border Areas of Western Cambodia,http://dx.doi.org/10.1371/journal.pone.0152529,PMC4814059,27028323,CC0,"Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1–77) presenting with influenza-like-illness (ILI) at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse transcriptase (rRT) PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. ILI-specimens negative for influenza were cultured, followed by rRT-PCR for enterovirus and rhinovirus (EV/RV) and EV71. Influenza was found in 168 cases (29%) and occurred almost exclusively in the rainy season from June to November. Isolated influenza strains had close antigenic and phylogenetic relationships, matching vaccine and circulating strains found elsewhere in Cambodia. Influenza vaccination coverage was low (<20%). Western Cambodian H1N1(2009) isolate genomes were more closely related to 10 earlier Cambodia isolates (94.4% genome conservation) than to 13 Thai isolates (75.9% genome conservation), despite sharing the majority of the amino acid changes with the Thai references. Most genes showed signatures of purifying selection. Viral culture detected only adenovirus (5.7%) and parainfluenza virus (3.8%), while non-polio enteroviruses (10.3%) were detected among 164 culture-negative samples including coxsackievirus A4, A6, A8, A9, A12, B3, B4 and echovirus E6 and E9 using nested RT-PCR methods. A single specimen of EV71 was found. Despite proximity to Thailand, influenza epidemiology of these western Cambodian isolates followed patterns observed elsewhere in Cambodia, continuing to support current vaccine and treatment recommendations from the Cambodian National Influenza Center. Amino acid mutations at non-epitope sites, particularly hemagglutinin genes, require further investigation in light of an increasingly important role of permissive mutations in influenza virus evolution. Further research about the burden of adenovirus and non-polio enteroviruses as etiologic agents in acute respiratory infections in Cambodia is also needed.",2016 Mar 30,"['Timmermans, Ans', 'Melendrez, Melanie C.', 'Se, Youry', 'Chuang, Ilin', 'Samon, Nou', 'Uthaimongkol, Nichapat', 'Klungthong, Chonticha', 'Manasatienkij, Wudtichai', 'Thaisomboonsuk, Butsaya', 'Tyner, Stuart D.', 'Rith, Sareth', 'Horm, Viseth Srey', 'Jarman, Richard G.', 'Bethell, Delia', 'Chanarat, Nitima', 'Pavlin, Julie', 'Wongstitwilairoong, Tippa', 'Saingam, Piyaporn', 'El, But Sam', 'Fukuda, Mark M.', 'Touch, Sok', 'Sovann, Ly', 'Fernandez, Stefan', 'Buchy, Philippe', 'Chanthap, Lon', 'Saunders, David']",PLoS One,,,True
68493ffac48a4fdbc15314a0a2bf5cabd087f853,PMC,The Hemagglutinin of Bat-Associated Influenza Viruses Is Activated by TMPRSS2 for pH-Dependent Entry into Bat but Not Human Cells,http://dx.doi.org/10.1371/journal.pone.0152134,PMC4814062,27028521,CC BY,"New World bats have recently been discovered to harbor influenza A virus (FLUAV)-related viruses, termed bat-associated influenza A-like viruses (batFLUAV). The internal proteins of batFLUAV are functional in mammalian cells. In contrast, no biological functionality could be demonstrated for the surface proteins, hemagglutinin (HA)-like (HAL) and neuraminidase (NA)-like (NAL), and these proteins need to be replaced by their human counterparts to allow spread of batFLUAV in human cells. Here, we employed rhabdoviral vectors to study the role of HAL and NAL in viral entry. Vectors pseudotyped with batFLUAV-HAL and -NAL were able to enter bat cells but not cells from other mammalian species. Host cell entry was mediated by HAL and was dependent on prior proteolytic activation of HAL and endosomal low pH. In contrast, sialic acids were dispensable for HAL-driven entry. Finally, the type II transmembrane serine protease TMPRSS2 was able to activate HAL for cell entry indicating that batFLUAV can utilize human proteases for HAL activation. Collectively, these results identify viral and cellular factors governing host cell entry driven by batFLUAV surface proteins. They suggest that the absence of a functional receptor precludes entry of batFLUAV into human cells while other prerequisites for entry, HAL activation and protonation, are met in target cells of human origin.",2016 Mar 30,"['Hoffmann, Markus', 'Krüger, Nadine', 'Zmora, Pawel', 'Wrensch, Florian', 'Herrler, Georg', 'Pöhlmann, Stefan']",PLoS One,,,True
c10d2b72f8d450209946e805ba18154c9a6c5f7f,PMC,Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor,http://dx.doi.org/10.1371/journal.ppat.1005531,PMC4814111,27027316,CC BY,"Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro) with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for further development for important coronaviruses in animals and humans.",2016 Mar 30,"['Kim, Yunjeong', 'Liu, Hongwei', 'Galasiti Kankanamalage, Anushka C.', 'Weerasekara, Sahani', 'Hua, Duy H.', 'Groutas, William C.', 'Chang, Kyeong-Ok', 'Pedersen, Niels C.']",PLoS Pathog,,,True
7bb64d780ff05f2e1ab0a912fdb77aca44652871,PMC,Mycoplasma pneumoniae: Current Knowledge on Nucleic Acid Amplification Techniques and Serological Diagnostics,http://dx.doi.org/10.3389/fmicb.2016.00448,PMC4814781,27064893,CC BY,"Mycoplasma pneumoniae (M. pneumoniae) belongs to the class Mollicutes and has been recognized as a common cause of respiratory tract infections (RTIs), including community-acquired pneumonia (CAP), that occur worldwide and in all age groups. In addition, M. pneumoniae can simultaneously or sequentially lead to damage in the nervous system and has been associated with a wide variety of other acute and chronic diseases. During the past 10 years, the proportion of LRTI in children and adults, associated with M. pneumoniae infection has ranged from 0 to more than 50%. This variation is due to the age and the geographic location of the population examined but also due to the diagnostic methods used. The true role of M. pneumoniae in RTIs remains a challenge given the many limitations and lack of standardization of the applied diagnostic tool in most cases, with resultant wide variations in data from different studies. Correct and rapid diagnosis and/or management of M. pneumoniae infections is, however, critical to initiate appropriate antibiotic treatment and is nowadays usually done by PCR and/or serology. Several recent reviews, have summarized current methods for the detection and identification of M. pneumoniae. This review will therefore provide a look at the general principles, advantages, diagnostic value, and limitations of the most currently used detection techniques for the etiological diagnosis of a M. pneumoniae infection as they evolve from research to daily practice.",2016 Mar 31,"['Loens, Katherine', 'Ieven, Margareta']",Front Microbiol,,,True
ac04992c38f8d8bb758a7460e350827c390698a1,PMC,Clinical outcomes in outpatient respiratory syncytial virus infection in immunocompromised children,http://dx.doi.org/10.1111/irv.12375,PMC4814860,26859306,CC BY,"BACKGROUND: Immunocompromised patients are at high risk for morbidity and mortality due to respiratory syncytial virus (RSV) infection. Increasingly, pediatric patients with malignancy or undergoing transplantation are managed primarily as outpatients. Data regarding the clinical presentation and outcomes of RSV in the outpatient pediatric immunocompromised population are limited. METHODS: We performed a retrospective cohort study of children with hematologic malignancy or hematopoietic or solid organ transplant with laboratory‐confirmed RSV infection diagnosed as outpatients at an academic medical center between 2008 and 2013. RESULTS: Of 54 patients with RSV detected while outpatients, 15 (28%) were hospitalized, 7 (13%) received ribavirin, and one (2%) received intravenous immunoglobulin. One (2%) patient was critically ill, but there were no deaths due to RSV infection. Fever (P < 0·01) was associated with increased risk of hospitalization. CONCLUSIONS: Most immunocompromised children with RSV detected while outpatients did not require hospitalization or receive antiviral treatment. Potential studies of RSV therapies should consider inclusion of patients in an ambulatory setting.",2016 May 23,"['Chu, Helen Y.', 'Chin, Jennifer', 'Pollard, Jessica', 'Zerr, Danielle M.', 'Englund, Janet A.']",Influenza Other Respir Viruses,,,True
0b0ce0d563375eba593f552fc31f82289982c829,PMC,"Surveillance for severe acute respiratory infections in Southern Arizona, 2010–2014",http://dx.doi.org/10.1111/irv.12360,PMC4814863,26590069,CC BY,"BACKGROUND: The Binational Border Infectious Disease Surveillance program began surveillance for severe acute respiratory infections (SARI) on the US–Mexico border in 2009. Here, we describe patients in Southern Arizona. METHODS: Patients admitted to five acute care hospitals that met the SARI case definition (temperature ≥37·8°C or reported fever or chills with history of cough, sore throat, or shortness of breath in a hospitalized person) were enrolled. Staff completed a standard form and collected a nasopharyngeal swab which was tested for selected respiratory viruses by reverse transcription polymerase chain reaction. RESULTS: From October 2010–September 2014, we enrolled 332 SARI patients. Fifty‐two percent were male and 48% were white non‐Hispanic. The median age was 63 years (47% ≥65 years and 5·2% <5 years). During hospitalization, 51 of 230 (22%) patients required intubation, 120 of 297 (40%) were admitted to intensive care unit, and 28 of 278 (10%) died. Influenza vaccination was 56%. Of 309 cases tested, 49 (16%) were positive for influenza viruses, 25 (8·1%) for human metapneumovirus, 20 (6·5%) for parainfluenza viruses, 16 (5·2%) for coronavirus, 11 (3·6%) for respiratory syncytial virus, 10 (3·2%) for rhinovirus, 4 (1·3%) for rhinovirus/enterovirus, 3 (1·0%) for enteroviruses, and 3 (1·0%) for adenovirus. Among the 49 influenza‐positive specimens, 76% were influenza A (19 H3N2, 17 H1N1pdm09, and 1 not subtyped), and 24% were influenza B. CONCLUSION: Influenza viruses were a frequent cause of SARI in hospitalized patients in Southern Arizona. Monitoring respiratory illness in border populations will help better understand the etiologies. Improving influenza vaccination coverage may help prevent some SARI cases.",2016 May 29,"['Wansaula, Zimy', 'Olsen, Sonja J.', 'Casal, Mariana G.', 'Golenko, Catherine', 'Erhart, Laura M.', 'Kammerer, Peter', 'Whitfield, Natalie', 'McCotter, Orion Z.']",Influenza Other Respir Viruses,,,True
8233e375e79b4e93b9d9a614d44762dba52b342f,PMC,Serotype and genetic diversity of human rhinovirus strains that circulated in Kenya in 2008,http://dx.doi.org/10.1111/irv.12373,PMC4814864,26822469,CC BY,"BACKGROUND: Human rhinoviruses (HRVs) are a well‐established cause of the common cold and recent studies indicated that they may be associated with severe acute respiratory illnesses (SARIs) like pneumonia, asthma, and bronchiolitis. Despite global studies on the genetic diversity of the virus, the serotype diversity of these viruses across diverse geographic regions in Kenya has not been characterized. OBJECTIVES: This study sought to characterize the serotype diversity of HRV strains that circulated in Kenya in 2008. METHODS: A total of 517 archived nasopharyngeal samples collected in a previous respiratory virus surveillance program across Kenya in 2008 were selected. Participants enrolled were outpatients who presented with influenza‐like (ILI) symptoms. Real‐time RT‐PCR was employed for preliminary HRV detection. HRV‐positive samples were amplified using RT‐PCR and thereafter the nucleotide sequences of the amplicons were determined followed by phylogenetic analysis. RESULTS: Twenty‐five percent of the samples tested positive for HRV. Phylogenetic analysis revealed that the Kenyan HRVs clustered into three main species comprising HRV‐A (54%), HRV‐B (12%), and HRV‐C (35%). Overall, 20 different serotypes were identified. Intrastrain sequence homology among the Kenyan strains ranged from 58% to 100% at the nucleotide level and 55% to 100% at the amino acid level. CONCLUSION: These results show that a wide range of HRV serotypes with different levels of nucleotide variation were present in Kenya. Furthermore, our data show that HRVs contributed substantially to influenza‐like illness in Kenya in 2008.",2016 May 2,"['Milanoi, Sylvia', 'Ongus, Juliette R.', 'Gachara, George', 'Coldren, Rodney', 'Bulimo, Wallace']",Influenza Other Respir Viruses,,,True
6312f554c8e95f9c8f3b5c0b150d88d35d657ae2,PMC,EV‐D68 infection in children with asthma exacerbation and pneumonia in Mexico City during 2014 autumn,http://dx.doi.org/10.1111/irv.12384,PMC4814865,26935868,CC BY,"BACKGROUND: Human enterovirus D68 (EV‐D68) recently caused an increase in mild‐to‐severe pediatric respiratory cases in North America and some European countries. Even though few of these children presented with acute paralytic disease, direct causal relationship cannot yet be assumed. OBJECTIVES: The purposes of this report were to describe the clinical findings of an outbreak of EV‐D68 infection in Mexico City and identify the genetic relationship with previously reported strains. PATIENTS/METHODS: Between September and December 2014, 126 nasopharyngeal samples (NPS) of hospitalized children <15 years of age with ARI were tested for the presence of respiratory viruses using a multiplex RT‐qPCR and EV‐D68‐specific RT‐qPCR. Clinical, epidemiological, and demographic data were collected and associated with symptomatology and viral infections. Phylogenetic analyses were performed using VP1 region. RESULTS: Enterovirus/rhinovirus infection was detected in 40 patients (31·7%), of which 24 patients were EV‐D68‐positive. EV‐D68 infection prevailed over September and October 2014 and was associated with neutrophilia and lymphopenia, and patients were more likely to develop hypoxemia. Phylogenetic analyses showed that Mexican EV‐D68 belongs to the new B1 clade. CONCLUSIONS: This is the first EV‐D68 outbreak described in Mexico and occurred few weeks after the United States reported similar infections. Although EV‐D68 belongs to new B1 clade, no neurological affection was observed.",2016 May 31,"['Vazquez‐Perez, Joel A.', 'Ramirez‐Gonzalez, Jose E.', 'Moreno‐Valencia, Yazmin', 'Hernandez‐Hernandez, Victor A.', 'Romero‐Espinoza, Jose A. I.', 'Castillejos‐Lopez, Manuel', 'Hernandez, Andres', 'Perez‐Padilla, Rogelio', 'Oropeza‐Lopez, Lizbeth E.', 'Escobar‐Escamilla, Noe', 'Gonzalez‐Villa, Maribel', 'Alejandre‐Garcia, Alejandro', 'Regalado‐Pineda, Justino', 'Santillan‐Doherty, Patricio', 'Lopez‐Martínez, Irma', 'Diaz‐Quiñonez, Alberto', 'Salas‐Hernandez, Jorge']",Influenza Other Respir Viruses,,,True
668aeb98c355caf8edcbbcb808215f26e7c388ad,PMC,Autophagy Negatively Regulates Transmissible Gastroenteritis Virus Replication,http://dx.doi.org/10.1038/srep23864,PMC4814908,27029407,CC BY,"Autophagy is an evolutionarily ancient pathway that has been shown to be important in the innate immune defense against several viruses. However, little is known about the regulatory role of autophagy in transmissible gastroenteritis virus (TGEV) replication. In this study, we found that TGEV infection increased the number of autophagosome-like double- and single-membrane vesicles in the cytoplasm of host cells, a phenomenon that is known to be related to autophagy. In addition, virus replication was required for the increased amount of the autophagosome marker protein LC3-II. Autophagic flux occurred in TGEV-infected cells, suggesting that TGEV infection triggered a complete autophagic response. When autophagy was pharmacologically inhibited by wortmannin or LY294002, TGEV replication increased. The increase in virus yield via autophagy inhibition was further confirmed by the use of siRNA duplexes, through which three proteins required for autophagy were depleted. Furthermore, TGEV replication was inhibited when autophagy was activated by rapamycin. The antiviral response of autophagy was confirmed by using siRNA to reduce the expression of gene p300, which otherwise inhibits autophagy. Together, the results indicate that TGEV infection activates autophagy and that autophagy then inhibits further TGEV replication.",2016 Mar 31,"['Guo, Longjun', 'Yu, Haidong', 'Gu, Weihong', 'Luo, Xiaolei', 'Li, Ren', 'Zhang, Jian', 'Xu, Yunfei', 'Yang, Lijun', 'Shen, Nan', 'Feng, Li', 'Wang, Yue']",Sci Rep,,,True
6bb3d6f24023746ace0ede108d88a4ed1f6e2e0d,PMC,Autophagy Negatively Regulates Transmissible Gastroenteritis Virus Replication,http://dx.doi.org/10.1038/srep23864,PMC4814908,27029407,CC BY,"Autophagy is an evolutionarily ancient pathway that has been shown to be important in the innate immune defense against several viruses. However, little is known about the regulatory role of autophagy in transmissible gastroenteritis virus (TGEV) replication. In this study, we found that TGEV infection increased the number of autophagosome-like double- and single-membrane vesicles in the cytoplasm of host cells, a phenomenon that is known to be related to autophagy. In addition, virus replication was required for the increased amount of the autophagosome marker protein LC3-II. Autophagic flux occurred in TGEV-infected cells, suggesting that TGEV infection triggered a complete autophagic response. When autophagy was pharmacologically inhibited by wortmannin or LY294002, TGEV replication increased. The increase in virus yield via autophagy inhibition was further confirmed by the use of siRNA duplexes, through which three proteins required for autophagy were depleted. Furthermore, TGEV replication was inhibited when autophagy was activated by rapamycin. The antiviral response of autophagy was confirmed by using siRNA to reduce the expression of gene p300, which otherwise inhibits autophagy. Together, the results indicate that TGEV infection activates autophagy and that autophagy then inhibits further TGEV replication.",2016 Mar 31,"['Guo, Longjun', 'Yu, Haidong', 'Gu, Weihong', 'Luo, Xiaolei', 'Li, Ren', 'Zhang, Jian', 'Xu, Yunfei', 'Yang, Lijun', 'Shen, Nan', 'Feng, Li', 'Wang, Yue']",Sci Rep,,,False
3f1a7bb419c2658dfd71663cc87efd03a38f1716,PMC,Quantitative Proteomic Analysis of Duck Ovarian Follicles Infected with Duck Tembusu Virus by Label-Free LC-MS,http://dx.doi.org/10.3389/fmicb.2016.00463,PMC4815560,27066001,CC BY,"Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused massive economic losses to the duck industry in China. DTMUV infection mainly results in significant decreases in egg production in egg-laying ducks within 1–2 weeks post infection. However, information on the comparative protein expression of host tissues in response to DTMUV infection is limited. In the present study, the cellular protein response to DTMUV infection in duck ovarian follicles was analyzed using nano-flow high-performance liquid chromatography-electrospray tandem mass spectrometry. Quantitative proteomic analysis revealed 131 differentially expressed proteins, among which 53 were up regulated and 78 were down regulated. The identified proteins were involved in the regulation of essential processes such as cellular structure and integrity, RNA processing, protein biosynthesis and modification, vesicle transport, signal transduction, and mitochondrial pathway. Some selected proteins that were found to be regulated in DTMUV-infected tissues were screened by quantitative real-time PCR to examine their regulation at the transcriptional level, western blot analysis was used to validate the changes of some selected proteins on translational level. To our knowledge, this study is the first to analyze the proteomic changes in duck ovarian follicles following DTMUV infection. The protein-related information obtained in this study may be useful to understand the host response to DTMUV infection and the inherent mechanism of DTMUV replication and pathogenicity.",2016 Mar 31,"['Han, Kaikai', 'Zhao, Dongmin', 'Liu, Yuzhuo', 'Liu, Qingtao', 'Huang, Xinmei', 'Yang, Jing', 'An, Fengjiao', 'Li, Yin']",Front Microbiol,,,True
33d46081e98cd5a3b1152ecee6361ae8f9f89ea9,PMC,Clinical Presentation and Birth Outcomes Associated with Respiratory Syncytial Virus Infection in Pregnancy,http://dx.doi.org/10.1371/journal.pone.0152015,PMC4816499,27031702,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of viral pneumonia in children worldwide. A maternal vaccine may protect both the mother and infant from RSV illness. The epidemiology and clinical presentation of RSV in pregnant and postpartum women is not well-described. METHODS: Data were collected from a prospective, randomized trial of influenza immunization in pregnant women in rural southern Nepal. Women were enrolled in their second trimester of pregnancy and followed until six months postpartum. Active weekly home-based surveillance for febrile respiratory illness was performed. Mid-nasal swabs collected with episodes of respiratory illness were tested for RSV by real-time polymerase chain reaction. RESULTS: RSV was detected in 14 (0.4%) illness episodes in 3693 women over 3554 person-years of surveillance from 2011–2014. RSV incidence was 3.9/1000 person-years overall, and 11.8/1000 person-years between September and December. Seven (50%) women sought care for RSV illness; none died. Of the 7 (50%) illness episodes during pregnancy, all had live births with 2 (29%) preterm births and a median birthweight of 3060 grams. This compares to 469 (13%) preterm births and a median birthweight of 2790 grams in women without RSV during pregnancy. Of the 7 mothers with postpartum RSV infection, RSV was detected in 4 (57%) of their infants. CONCLUSIONS: RSV was an uncommon cause of febrile respiratory illness in mothers during pregnancy in Nepal. These data will inform prevention and therapeutic strategies against RSV in resource-limited settings.",2016 Mar 31,"['Chu, Helen Y.', 'Katz, Joanne', 'Tielsch, James', 'Khatry, Subarna K.', 'Shrestha, Laxman', 'LeClerq, Steven C.', 'Magaret, Amalia', 'Kuypers, Jane', 'Steinhoff, Mark C.', 'Englund, Janet A.']",PLoS One,,,True
15753984412d073dd4c6daed84e3d294f728b636,PMC,Emergence of a Large-Plaque Variant in Mice Infected with Coxsackievirus B3,http://dx.doi.org/10.1128/mBio.00119-16,PMC4817249,27025249,CC BY,"Coxsackieviruses are enteric viruses that frequently infect humans. To examine coxsackievirus pathogenesis, we orally inoculated mice with the coxsackievirus B3 (CVB3) Nancy strain. Using HeLa cell plaque assays with agar overlays, we noticed that some fecal viruses generated plaques >100 times as large as inoculum viruses. These large-plaque variants emerged following viral replication in several different tissues. We identified a single amino acid change, N63Y, in the VP3 capsid protein that was sufficient to confer the large-plaque phenotype. Wild-type CVB3 and N63Y mutant CVB3 had similar plaque sizes when agarose was used in the overlay instead of agar. We determined that sulfated glycans in agar inhibited plaque formation by wild-type CVB3 but not by N63Y mutant CVB3. Furthermore, N63Y mutant CVB3 bound heparin, a sulfated glycan, less efficiently than wild-type CVB3 did. While N63Y mutant CVB3 had a growth defect in cultured cells and reduced attachment, it had enhanced replication and pathogenesis in mice. Infection with N63Y mutant CVB3 induced more severe hepatic damage than infection with wild-type CVB3, likely because N63Y mutant CVB3 disseminates more efficiently to the liver. Our data reinforce the idea that culture-adapted laboratory virus strains can have reduced fitness in vivo. N63Y mutant CVB3 may be useful as a platform to understand viral adaptation and pathogenesis in animal studies.",2016 Mar 29,"['Wang, Yao', 'Pfeiffer, Julie K.']",mBio,,,True
21d0dff90077800702fb5a6502246e9d512b6fe8,PMC,Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation,http://dx.doi.org/10.1128/mBio.00258-16,PMC4817253,27025250,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins that are not required for replication of the genome but are likely involved in pathogenesis. Evasion of host innate immunity through interferon (IFN) antagonism is a critical component of viral pathogenesis. The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway activates upon sensing of viral double-stranded RNA (dsRNA). Activated RNase L cleaves viral and host single-stranded RNA (ssRNA), which leads to translational arrest and subsequent cell death, preventing viral replication and spread. Here we report that MERS-CoV, a lineage C Betacoronavirus, and related bat CoV NS4b accessory proteins have phosphodiesterase (PDE) activity and antagonize OAS-RNase L by enzymatically degrading 2′,5′-oligoadenylate (2-5A), activators of RNase L. This is a novel function for NS4b, which has previously been reported to antagonize IFN signaling. NS4b proteins are distinct from lineage A Betacoronavirus PDEs and rotavirus gene-encoded PDEs, in having an amino-terminal nuclear localization signal (NLS) and are localized mostly to the nucleus. However, the expression level of cytoplasmic MERS-CoV NS4b protein is sufficient to prevent activation of RNase L. Finally, this is the first report of an RNase L antagonist expressed by a human or bat coronavirus and provides a specific mechanism by which this occurs. Our findings provide a potential mechanism for evasion of innate immunity by MERS-CoV while also identifying a potential target for therapeutic intervention.",2016 Mar 29,"['Thornbrough, Joshua M.', 'Jha, Babal K.', 'Yount, Boyd', 'Goldstein, Stephen A.', 'Li, Yize', 'Elliott, Ruth', 'Sims, Amy C.', 'Baric, Ralph S.', 'Silverman, Robert H.', 'Weiss, Susan R.']",mBio,,,True
a7b1bcb7b1806dce219451f289d56b14434f7ac1,PMC,S1 domain of the porcine epidemic diarrhea virus spike protein as a vaccine antigen,http://dx.doi.org/10.1186/s12985-016-0512-8,PMC4818391,27036203,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is a highly contagious virus infecting pigs of all ages with high morbidity and mortality among newborn piglets. Currently, there is no effective vaccine available to protect the pigs from PEDV. The N-terminal subunit of spike protein (S1) is responsible for virus binding to the cellular receptor and contains a number of neutralizing antibody epitopes. Thus, we expressed and produced recombinant S1 protein to protect newborn piglets by immunization of sows. METHODS: Affinity tagged PEDV S1 protein was expressed in a secretory form in yeast, insect and mammalian cells to identify the most suitable production system. Purified recombinant protein was analysed by SDS-PAGE, Western blot and deglycosylation assay. A pregnant sow was intramuscularly immunized three times with adjuvanted recombinant protein prior to farrowing. PEDV-specific immune responses in sera and colostrum of the sow and piglets were assayed by ELISA and virus neutralization assays. Piglets were challenged orally with PEDV, and clinical parameters were monitored for 6 days post-challenge. RESULTS AND CONCLUSION: Of three eukaryotic expression systems tested (yeast, insect-cell, and mammalian), expression by HEK-293 T cells gave the highest yield of protein that was N-glycosylated and was the most appropriate candidate for vaccination. Administration of the subunit vaccine in a sow resulted in induction of S1-specific IgG and IgA that were passively transferred to the suckling piglets. Also, high virus neutralization titres were observed in the serum of the vaccinated sow and its piglets. After PEDV challenge, piglets born to the vaccinated sow exhibited less severe signs of disease and significantly lower mortality compared to the piglets of a control sow. However, there were no significant differences in diarrhea, body weight and virus shedding. Thus, vaccination with S1 subunit vaccine failed to provide complete protection to suckling piglets after challenge exposure, and further improvements are needed for the development of a subunit vaccine that fully protects against PEDV infection.",2016 Apr 1,"['Makadiya, Niraj', 'Brownlie, Robert', 'van den Hurk, Jan', 'Berube, Nathalie', 'Allan, Brenda', 'Gerdts, Volker', 'Zakhartchouk, Alexander']",Virol J,,,True
34081c03e48678c7d7633e81cecdeb0b6dbf30e4,PMC,Nottingham Trent University and Makerere University School of Public Health partnership: experiences of co-learning and supporting the healthcare system in Uganda,http://dx.doi.org/10.1186/s12992-016-0148-x,PMC4818423,27036632,CC BY,"Partnerships between developed and developing country institutions are increasingly becoming important in addressing contemporary global health challenges faced by health systems. Inter-university health collaboration such as the Nottingham Trent University (UK) and Makerere University School of Public Health (Uganda) partnership provide opportunities for working together in training, research and service delivery while strengthening health systems. This paper shares the experiences, achievements and opportunities of this partnership in co-learning and supporting the health system in Uganda. This includes a project being implemented to strengthen the training, supervision and motivation of community health workers in rural Uganda. Training and research are a key focus of the partnership and have involved both staff and students of both institutions including guest lectures, seminars and conference presentations. The partnership’s collaboration with stakeholders such as the Ministry of Health (Uganda) and local health authorities has ensured participation necessary in supporting implementation of sustainable interventions. The partnership uses several channels such as email, telephone, Skype, Dropbox and WhatsApp which have been useful in maintaining constant and effective communication. The challenges faced by the partnership include lack of funding to support student mobility, and varying academic schedules of the two institutions. The experiences and prospects of this growing partnership can inform other collaborations in similar settings.",2016 Mar 28,"['Musoke, David', 'Gibson, Linda', 'Mukama, Trasias', 'Khalil, Yesmean', 'Ssempebwa, John C.']",Global Health,,,True
95af044a0d57fffb101b547ff1f58122d05771bb,PMC,Protecting health workers from infectious disease transmission: an exploration of a Canadian-South African partnership of partnerships,http://dx.doi.org/10.1186/s12992-016-0145-0,PMC4818531,27036516,CC BY,"BACKGROUND: Health workers are at high risk of acquiring infectious diseases at work, especially in low and middle-income countries (LMIC) with critical health human resource deficiencies and limited implementation of occupational health and infection control measures. Amidst increasing interest in international partnerships to address such issues, how best to develop such collaborations is being actively debated. In 2006, a partnership developed between occupational health and infection control experts in Canada and institutions in South Africa (including an institute with a national mandate to conduct research and provide guidance to protect health workers from infectious diseases and promote improved working conditions). This article describes the collaboration, analyzes the determinants of success and shares lessons learned. METHODS: Synthesizing participant-observer experience from over 9 years of collaboration and 10 studies already published from this work, we applied a realist review analysis to describe the various achievements at global, national, provincial and hospital levels. Expectations of the various parties on developing new insights, providing training, and addressing service needs were examined through a micro-meso-macro lens, focusing on how each main partner organization contributed to and benefitted from working together. RESULTS: A state-of-the-art occupational health and safety surveillance program was established in South Africa following successful technology transfer from a similar undertaking in Canada and training was conducted that synergistically benefitted Northern as well as Southern trainees. Integrated policies combining infection control and occupational health to prevent and control infectious disease transmission among health workers were also launched. Having a national (South-South) network reinforced by the international (North–south) partnership was pivotal in mitigating the challenges that emerged. CONCLUSIONS: High-income country partnerships with experience in health system strengthening – particularly in much needed areas such as occupational health and infection control – can effectively work through strong collaborators in the Global South to build capacity. Partnerships are particularly well positioned to sustainably reinforce efforts at national and sub-national LMIC levels when they adopt a “communities of practice” model, characterized by multi-directional learning. The principles of effective collaboration learned in this “partnership of partnerships” to improve working conditions for health workers can be applied to other areas where health system strengthening is needed.",2016 Mar 31,"['Yassi, Annalee', 'Zungu, Muzimkhulu', 'Spiegel, Jerry M.', 'Kistnasamy, Barry', 'Lockhart, Karen', 'Jones, David', 'O’Hara, Lyndsay M.', 'Nophale, Letshego', 'Bryce, Elizabeth A.', 'Darwin, Lincoln']",Global Health,,,True
3656fed9d1f687fd87440d7da4f3d852aa1dcdc4,PMC,Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis,http://dx.doi.org/10.15252/emmm.201505986,PMC4818751,26992832,CC BY,"Currently available rabies post‐exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad‐spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non‐RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post‐vaccination antibody response.",2016 Apr 18,"['De Benedictis, Paola', 'Minola, Andrea', 'Rota Nodari, Elena', 'Aiello, Roberta', 'Zecchin, Barbara', 'Salomoni, Angela', 'Foglierini, Mathilde', 'Agatic, Gloria', 'Vanzetta, Fabrizia', 'Lavenir, Rachel', 'Lepelletier, Anthony', 'Bentley, Emma', 'Weiss, Robin', 'Cattoli, Giovanni', 'Capua, Ilaria', 'Sallusto, Federica', 'Wright, Edward', 'Lanzavecchia, Antonio', 'Bourhy, Hervé', 'Corti, Davide']",EMBO Mol Med,,,True
f0dfa7ee5ac42ad3ab47c11f776fd5571b3b4fc1,PMC,Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis,http://dx.doi.org/10.15252/emmm.201505986,PMC4818751,26992832,CC BY,"Currently available rabies post‐exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad‐spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non‐RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post‐vaccination antibody response.",2016 Apr 18,"['De Benedictis, Paola', 'Minola, Andrea', 'Rota Nodari, Elena', 'Aiello, Roberta', 'Zecchin, Barbara', 'Salomoni, Angela', 'Foglierini, Mathilde', 'Agatic, Gloria', 'Vanzetta, Fabrizia', 'Lavenir, Rachel', 'Lepelletier, Anthony', 'Bentley, Emma', 'Weiss, Robin', 'Cattoli, Giovanni', 'Capua, Ilaria', 'Sallusto, Federica', 'Wright, Edward', 'Lanzavecchia, Antonio', 'Bourhy, Hervé', 'Corti, Davide']",EMBO Mol Med,,,False
b47215082b8b863141fa268157d54a1ea6c067eb,PMC,Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis,http://dx.doi.org/10.15252/emmm.201505986,PMC4818751,26992832,CC BY,"Currently available rabies post‐exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad‐spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non‐RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post‐vaccination antibody response.",2016 Apr 18,"['De Benedictis, Paola', 'Minola, Andrea', 'Rota Nodari, Elena', 'Aiello, Roberta', 'Zecchin, Barbara', 'Salomoni, Angela', 'Foglierini, Mathilde', 'Agatic, Gloria', 'Vanzetta, Fabrizia', 'Lavenir, Rachel', 'Lepelletier, Anthony', 'Bentley, Emma', 'Weiss, Robin', 'Cattoli, Giovanni', 'Capua, Ilaria', 'Sallusto, Federica', 'Wright, Edward', 'Lanzavecchia, Antonio', 'Bourhy, Hervé', 'Corti, Davide']",EMBO Mol Med,,,False
e793ed5d6d883cd196795a4ca5d1ae0fbe632b34,PMC,Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis,http://dx.doi.org/10.15252/emmm.201505986,PMC4818751,26992832,CC BY,"Currently available rabies post‐exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad‐spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non‐RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post‐vaccination antibody response.",2016 Apr 18,"['De Benedictis, Paola', 'Minola, Andrea', 'Rota Nodari, Elena', 'Aiello, Roberta', 'Zecchin, Barbara', 'Salomoni, Angela', 'Foglierini, Mathilde', 'Agatic, Gloria', 'Vanzetta, Fabrizia', 'Lavenir, Rachel', 'Lepelletier, Anthony', 'Bentley, Emma', 'Weiss, Robin', 'Cattoli, Giovanni', 'Capua, Ilaria', 'Sallusto, Federica', 'Wright, Edward', 'Lanzavecchia, Antonio', 'Bourhy, Hervé', 'Corti, Davide']",EMBO Mol Med,,,True
5864eb909b8a0b74359b9d4ae2ace23e41287159,PMC,Chances and challenges in China,http://dx.doi.org/10.1007/s13238-015-0235-4,PMC4818847,26687390,CC BY,,2016 Apr 19,"Tefsen, Boris",Protein Cell,,,True
586df9c5c975c38a6f646674374a1eb98d280f62,PMC,Small Non-coding RNAs Associated with Viral Infectious Diseases of Veterinary Importance: Potential Clinical Applications,http://dx.doi.org/10.3389/fvets.2016.00022,PMC4819147,27092305,CC BY,"MicroRNAs (miRNAs) represent a class of small non-coding RNA (sncRNA) molecules that can regulate mRNAs by inducing their degradation or by blocking translation. Considering that miRNAs are ubiquitous, stable, and conserved across animal species, it seems feasible to exploit them for clinical applications. Unlike in human viral diseases, where some miRNA-based molecules have progressed to clinical application, in veterinary medicine, this concept is just starting to come into view. Clinically, miRNAs could represent powerful diagnostic tools to pinpoint animal viral diseases and/or prognostic tools to follow up disease progression or remission. Additionally, the possible consequences of miRNA dysregulation make them potential therapeutic targets and open the possibilities to use them as tools to generate viral disease-resistant livestock. This review presents an update of preclinical studies on using sncRNAs to combat viral diseases that affect pet and farm animals. Moreover, we discuss the possibilities and challenges of bringing these bench-based discoveries to the veterinary clinic.",2016 Apr 4,"['Samir, Mohamed', 'Pessler, Frank']",Front Vet Sci,,,True
f6d1e68561dad02f11de4b9882893826bb6321a4,PMC,Harm reduction policy in Taiwan: toward a comprehensive understanding of its making and effects,http://dx.doi.org/10.1186/s12954-016-0101-6,PMC4819272,27044357,CC BY,"BACKGROUND: In response to the spread of HIV caused by needle sharing among injection drug users (IDUs), the Taiwan Centers for Disease Control implemented a pilot harm reduction program in 2005 that expanded nationwide in 2006. The policy led to a significant reduction in the number of HIV-positive cases among IDUs in 4 years. METHODS: This article aims to provide a critical evaluation of this harm reduction policy in Taiwan. The research leading to this article included a thorough literature review and in-depth interviews with 31 active policy participants, including people working in hospitals, the academia, non-governmental organizations, community pharmacies, the legal system, and health authorities at both the central and local levels. The collected data were analyzed on the basis of situational analysis. RESULTS: The article examines the policy success by showing how this policy was assembled and by exposing the frictions and adjustments during its formation and implementation. Inter-departmental conflicts within or without the government and the efforts to coordinate them are addressed, and the transnational dimensions of this harm reduction policy are also discussed. The article then reflects on the effects of the policy and asks where the line should be drawn between what is harm reduction and what is not. CONCLUSIONS: This case illustration reveals the complexity of understanding an assembled health policy that involves multiple participants. The article intends to render an analytic account to enable a comparison with similar policies in other countries.",2016 Apr 4,"Chen, Jia-shin",Harm Reduct J,,,True
7b5111143804a15cd9120956dd6f29e4e1dcc439,PMC,Detection of Clostridium perfringens alpha toxin gene in lambs by loop mediated isothermal amplification,http://dx.doi.org/10.14202/vetworld.2016.60-64,PMC4819352,27051186,CC BY,"AIM: The loop mediated isothermal amplification (LAMP) was standardized for rapid detection of Clostridium perfringens. MATERIALS AND METHODS: A total of 120 fecal samples were collected from enterotoxemia suspected lambs were used for screening of C. perfringens cpa gene by LAMP. The specificity of the LAMP amplified products was tested by digesting with restriction enzyme XmnI for alpha toxin gene. RESULTS: Out of 120 samples screened 112 (93.3%) samples were positive by both LAMP and polymerase chain reaction (PCR) for detection of cpa gene which indicated the equal sensitivity of both the tests. The enzyme produced single cut in 162 base pair amplified product of alpha toxin gene at 81 base pair resulting in a single band in gel electrophoresis. CONCLUSION: Both LAMP and PCR for detection of cpa gene indicated the equal sensitivity of both the tests. Standardization of LAMP reaction for amplification of epsilon and beta toxin genes will help to identify the C. perfringens toxin types from the clinical samples. The test could be a suitable alternative to the PCR in detection of toxin types without the help of sophisticated machinery like thermal cycler. Considering its simplicity in operation and high sensitivity, there is the potential use of this technique in clinical diagnosis and surveillance of infectious diseases.",2016 Jan 20,"['Radhika, B.', 'Kumar, N. Vinod', 'Sreenivasulu, D.']",Vet World,,,True
2ec6d0d83b08c9b4e1784e319978aff1930d5484,PMC,What Effect Did the Global Financial Crisis Have Upon Youth Wellbeing? Evidence From Four Australian Cohorts,http://dx.doi.org/10.1037/dev0000092,PMC4819495,26854968,CC BY,"Recent research has suggested significant negative effects of the Global Financial Crisis (GFC) on mental health and wellbeing. In this article, the authors suggest that the developmental period of late adolescence may be at particular risk of economic downturns. Harmonizing 4 longitudinal cohorts of Australian youth (N = 38,017), we estimate the impact of the GFC on 1 general and 11 domain specific measures of wellbeing at age 19 and 22. Significant differences in wellbeing in most life domains were found, suggesting that wellbeing is susceptible to economic shocks. Given that the GFC in Australia was relatively mild, the finding of clear negative effects across 2 ages is of international concern.",2016 Apr 8,"['Parker, Philip D.', 'Jerrim, John', 'Anders, Jake']",Dev Psychol,,,True
d4f1ccfcf8b71a2828f39991e67142dd3a57fd1a,PMC,Comparative genomic analysis of pre-epidemic and epidemic Zika virus strains for virological factors potentially associated with the rapidly expanding epidemic,http://dx.doi.org/10.1038/emi.2016.48,PMC4820678,26980239,CC BY,"Less than 20 sporadic cases of human Zika virus (ZIKV) infection were reported in Africa and Asia before 2007, but large outbreaks involving up to 73% of the populations on the Pacific islands have started since 2007, and spread to the Americas in 2014. Moreover, the clinical manifestation of ZIKV infection has apparently changed, as evident by increasing reports of neurological complications, such as Guillain–Barré syndrome in adults and congenital anomalies in neonates. We comprehensively compared the genome sequences of pre-epidemic and epidemic ZIKV strains with complete genome or complete polyprotein sequences available in GenBank. Besides the reported phylogenetic clustering of the epidemic strains with the Asian lineage, we found that the topology of phylogenetic tree of all coding regions is the same except that of the non-structural 2B (NS2B) coding region. This finding was confirmed by bootscan analysis and multiple sequence alignment, which suggested the presence of a fragment of genetic recombination at NS2B with that of Spondweni virus. Moreover, the representative epidemic strain possesses one large bulge of nine bases instead of an external loop on the first stem-loop structure at the 3′-untranslated region just distal to the stop codon of the NS5 in the 1947 pre-epidemic prototype strain. Fifteen amino acid substitutions are found in the epidemic strains when compared with the pre-epidemic strains. As mutations in other flaviviruses can be associated with changes in virulence, replication efficiency, antigenic epitopes and host tropism, further studies would be important to ascertain the biological significance of these genomic changes.",2016 Mar 16,"['Zhu, Zheng', 'Chan, Jasper Fuk-Woo', 'Tee, Kah-Meng', 'Choi, Garnet Kwan-Yue', 'Lau, Susanna Kar-Pui', 'Woo, Patrick Chiu-Yat', 'Tse, Herman', 'Yuen, Kwok-Yung']",Emerg Microbes Infect,,,True
c798225c8b1b45e38fcd6163a711500c1f667b03,PMC,Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3,http://dx.doi.org/10.1038/srep24029,PMC4820770,27046158,CC BY,"Interferon-inducible transmembrane protein IFITM3 was known to restrict the entry of a wide spectrum of viruses to the cytosol of the host. The mechanism used by the protein to restrict viral entry is unclear given the unavailability of the membrane topology and structures of the IFITM family proteins. Systematic site-directed spin labeling (SDSL) and electron paramagnetic resonance (EPR) studies of IFITM3 in detergent micelles identified a single, long transmembrane helix in the C-terminus and an intramembrane segment in the N-terminal hydrophobic region. Solution NMR studies of the same sample verified the secondary structure distribution and demonstrated two rigid regions interacting with the micellar surface. The resulting membrane topology of IFITM3 supports the mechanism of an enhanced restricted membrane hemi-fusion.",2016 Apr 5,"['Ling, Shenglong', 'Zhang, Chengwei', 'Wang, Wei', 'Cai, Xiaoying', 'Yu, Lu', 'Wu, Fangming', 'Zhang, Longhua', 'Tian, Changlin']",Sci Rep,,,True
5846be53e7718e1a6ffae34ed5136693fd462bd8,PMC,Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3,http://dx.doi.org/10.1038/srep24029,PMC4820770,27046158,CC BY,"Interferon-inducible transmembrane protein IFITM3 was known to restrict the entry of a wide spectrum of viruses to the cytosol of the host. The mechanism used by the protein to restrict viral entry is unclear given the unavailability of the membrane topology and structures of the IFITM family proteins. Systematic site-directed spin labeling (SDSL) and electron paramagnetic resonance (EPR) studies of IFITM3 in detergent micelles identified a single, long transmembrane helix in the C-terminus and an intramembrane segment in the N-terminal hydrophobic region. Solution NMR studies of the same sample verified the secondary structure distribution and demonstrated two rigid regions interacting with the micellar surface. The resulting membrane topology of IFITM3 supports the mechanism of an enhanced restricted membrane hemi-fusion.",2016 Apr 5,"['Ling, Shenglong', 'Zhang, Chengwei', 'Wang, Wei', 'Cai, Xiaoying', 'Yu, Lu', 'Wu, Fangming', 'Zhang, Longhua', 'Tian, Changlin']",Sci Rep,,,False
de2da69b84bad743d1e16d52a12d4ea8ca9f66d9,PMC,Evaluation of serological cross-reactivity and cross-neutralization between the United States porcine epidemic diarrhea virus prototype and S-INDEL-variant strains,http://dx.doi.org/10.1186/s12917-016-0697-5,PMC4820917,27044253,CC BY,"BACKGROUND: At least two genetically different porcine epidemic diarrhea virus (PEDV) strains have been identified in the United States (U.S. PEDV prototype and S-INDEL-variant strains). The current serological assays offered at veterinary diagnostic laboratories for detection of PEDV-specific antibody are based on the U.S. PEDV prototype strain. The objectives of this study were: 1) isolate the U.S. PEDV S-INDEL-variant strain in cell culture; 2) generate antisera against the U.S. PEDV prototype and S-INDEL-variant strains by experimentally infecting weaned pigs; 3) determine if the various PEDV serological assays could detect antibodies against the U.S. PEDV S-INDEL-variant strain and vice versa. RESULTS: A U.S. PEDV S-INDEL-variant strain was isolated in cell culture in this study. Three groups of PEDV-negative, 3-week-old pigs (five pigs per group) were inoculated orally with a U.S. PEDV prototype isolate (previously isolated in our lab), an S-INDEL-variant isolate or virus-negative culture medium. Serum samples collected at 0, 7, 14, 21 and 28 days post inoculation were evaluated by the following PEDV serological assays: 1) indirect fluorescent antibody (IFA) assays using the prototype and S-INDEL-variant strains as indicator viruses; 2) virus neutralization (VN) tests against the prototype and S-INDEL-variant viruses; 3) PEDV prototype strain whole virus based ELISA; 4) PEDV prototype strain S1-based ELISA; and 5) PEDV S-INDEL-variant strain S1-based ELISA. The positive antisera against the prototype strain reacted to and neutralized both prototype and S-INDEL-variant viruses, and the positive antisera against the S-INDEL-variant strain also reacted to and neutralized both prototype and S-INDEL-variant viruses, as examined by IFA antibody assays and VN tests. Antibodies against the two PEDV strains could be detected by all three ELISAs although detection rates varied to some degree. CONCLUSIONS: These data indicate that the antibodies against U.S. PEDV prototype and S-INDEL-variant strains cross-reacted and cross-neutralized both strains in vitro. The current serological assays based on U.S. PEDV prototype strain can detect antibodies against both U.S. PEDV strains.",2016 Apr 5,"['Chen, Qi', 'Thomas, Joseph T.', 'Giménez-Lirola, Luis G.', 'Hardham, John M.', 'Gao, Qinshan', 'Gerber, Priscilla F.', 'Opriessnig, Tanja', 'Zheng, Ying', 'Li, Ganwu', 'Gauger, Phillip C.', 'Madson, Darin M.', 'Magstadt, Drew R.', 'Zhang, Jianqiang']",BMC Vet Res,,,True
1d613eb26d86e376a5f8cb5fdb673b7254110936,PMC,Bayesian Monitoring of Emerging Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0152629,PMC4821533,27045370,CC BY,"We define data analyses to monitor a change in R, the average number of secondary cases caused by a typical infected individual. The input dataset consists of incident cases partitioned into outbreaks, each initiated from a single index case. We split the input dataset into two successive subsets, to evaluate two successive R values, according to the Bayesian paradigm. We used the Bayes factor between the model with two different R values and that with a single R value to justify that the change in R is statistically significant. We validated our approach using simulated data, generated using known R. In particular, we found that claiming two distinct R values may depend significantly on the number of outbreaks. We then reanalyzed data previously studied by Jansen et al. [Jansen et al. Science 301 (5634), 804], concerning the effective reproduction number for measles in the UK, during 1995–2002. Our analyses showed that the 1995–2002 dataset should be divided into two separate subsets for the periods 1995–1998 and 1999–2002. In contrast, Jansen et al. take this splitting point as input of their analysis. Our estimated effective reproduction numbers R are in good agreement with those found by Jansen et al. In conclusion, our methodology for detecting temporal changes in R using outbreak-size data worked satisfactorily with both simulated and real-world data. The methodology may be used for updating R in real time, as surveillance outbreak data become available.",2016 Apr 5,"['Polyakov, Pavel', 'Breban, Romulus']",PLoS One,,,True
567942b67459da90977129ef385ef9f6a2133abb,PMC,The new (dis)order in RNA regulation,http://dx.doi.org/10.1186/s12964-016-0132-3,PMC4822317,27048167,CC BY,"RNA-binding proteins play a key role in the regulation of all aspects of RNA metabolism, from the synthesis of RNA to its decay. Protein-RNA interactions have been thought to be mostly mediated by canonical RNA-binding domains that form stable secondary and tertiary structures. However, a number of pioneering studies over the past decades, together with recent proteome-wide data, have challenged this view, revealing surprising roles for intrinsically disordered protein regions in RNA binding. Here, we discuss how disordered protein regions can mediate protein-RNA interactions, conceptually grouping these regions into RS-rich, RG-rich, and other basic sequences, that can mediate both specific and non-specific interactions with RNA. Disordered regions can also influence RNA metabolism through protein aggregation and hydrogel formation. Importantly, protein-RNA interactions mediated by disordered regions can influence nearly all aspects of co- and post-transcriptional RNA processes and, consequently, their disruption can cause disease. Despite growing interest in disordered protein regions and their roles in RNA biology, their mechanisms of binding, regulation, and physiological consequences remain poorly understood. In the coming years, the study of these unorthodox interactions will yield important insights into RNA regulation in cellular homeostasis and disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12964-016-0132-3) contains supplementary material, which is available to authorized users.",2016 Apr 6,"['Järvelin, Aino I.', 'Noerenberg, Marko', 'Davis, Ilan', 'Castello, Alfredo']",Cell Commun Signal,,,False
532f2c636fca1caae1f23885b9dc0e3302a0afd5,PMC,The new (dis)order in RNA regulation,http://dx.doi.org/10.1186/s12964-016-0132-3,PMC4822317,27048167,CC BY,"RNA-binding proteins play a key role in the regulation of all aspects of RNA metabolism, from the synthesis of RNA to its decay. Protein-RNA interactions have been thought to be mostly mediated by canonical RNA-binding domains that form stable secondary and tertiary structures. However, a number of pioneering studies over the past decades, together with recent proteome-wide data, have challenged this view, revealing surprising roles for intrinsically disordered protein regions in RNA binding. Here, we discuss how disordered protein regions can mediate protein-RNA interactions, conceptually grouping these regions into RS-rich, RG-rich, and other basic sequences, that can mediate both specific and non-specific interactions with RNA. Disordered regions can also influence RNA metabolism through protein aggregation and hydrogel formation. Importantly, protein-RNA interactions mediated by disordered regions can influence nearly all aspects of co- and post-transcriptional RNA processes and, consequently, their disruption can cause disease. Despite growing interest in disordered protein regions and their roles in RNA biology, their mechanisms of binding, regulation, and physiological consequences remain poorly understood. In the coming years, the study of these unorthodox interactions will yield important insights into RNA regulation in cellular homeostasis and disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12964-016-0132-3) contains supplementary material, which is available to authorized users.",2016 Apr 6,"['Järvelin, Aino I.', 'Noerenberg, Marko', 'Davis, Ilan', 'Castello, Alfredo']",Cell Commun Signal,,,True
ad4dc41b48d9f6024088cb6c65a51972d928d200,PMC,Predicting and Evaluating the Epidemic Trend of Ebola Virus Disease in the 2014-2015 Outbreak and the Effects of Intervention Measures,http://dx.doi.org/10.1371/journal.pone.0152438,PMC4822846,27049322,CC BY,"We constructed dynamic Ebola virus disease (EVD) transmission models to predict epidemic trends and evaluate intervention measure efficacy following the 2014 EVD epidemic in West Africa. We estimated the effective vaccination rate for the population, with basic reproduction number (R(0)) as the intermediate variable. Periodic EVD fluctuation was analyzed by solving a Jacobian matrix of differential equations based on a SIR (susceptible, infective, and removed) model. A comprehensive compartment model was constructed to fit and predict EVD transmission patterns, and to evaluate the effects of control and prevention measures. Effective EVD vaccination rates were estimated to be 42% (31–50%), 45% (42–48%), and 51% (44–56%) among susceptible individuals in Guinea, Liberia and Sierra Leone, respectively. In the absence of control measures, there would be rapid mortality in these three countries, and an EVD epidemic would be likely recur in 2035, and then again 8~9 years later. Oscillation intervals would shorten and outbreak severity would decrease until the periodicity reached ~5.3 years. Measures that reduced the spread of EVD included: early diagnosis, treatment in isolation, isolating/monitoring close contacts, timely corpse removal, post-recovery condom use, and preventing or quarantining imported cases. EVD may re-emerge within two decades without control and prevention measures. Mass vaccination campaigns and control and prevention measures should be instituted to prevent future EVD epidemics.",2016 Apr 6,"['Guo, Zuiyuan', 'Xiao, Dan', 'Li, Dongli', 'Wang, Xiuhong', 'Wang, Yayu', 'Yan, Tiecheng', 'Wang, Zhiqi']",PLoS One,,,True
996fc493a4d72390383d242d35515dc8144bb36d,PMC,Does Circulating Antibody Play a Role in the Protection of Piglets against Porcine Epidemic Diarrhea Virus?,http://dx.doi.org/10.1371/journal.pone.0153041,PMC4822964,27050556,CC BY,"The contribution of circulating antibody to the protection of naïve piglets against porcine epidemic diarrhea virus (PEDV) was evaluated using a passive antibody transfer model. Piglets (n = 62) derived from 6 sows were assigned to one of 6 different treatments using a randomized block design which provided for allocation of all treatments to all sows' litters. Each treatment was designed to achieve a different level of circulating anti-PEDV antibody via intraperitoneally administration of concentrated serum antibody. Piglets were orally inoculated with PEDV (USA/IN/2013/19338E, 1 x 10(3) TCID(50) per piglet) 24 hours later and then monitored for 14 days. Piglets remained with their dam throughout the experiment. Sow milk samples, piglet fecal samples, and data on piglet clinical signs, body weight, and body temperature were collected daily. Fecal samples were tested by PEDV real-time reverse transcriptase PCR. Serum, colostrum, and milk were tested for PEDV IgG, IgA, and virus-neutralizing antibody. The data were evaluated for the effects of systemic PEDV antibody levels on growth, body temperature, fecal shedding, survival, and antibody response. The analysis showed that circulating antibody partially ameliorated the effect of PEDV infection. Specifically, antibody-positive groups returned to normal body temperature faster and demonstrated a higher rate of survivability than piglets without PEDV antibody. When combined with previous literature on PEDV, it can be concluded that both systemic antibodies and maternal secretory IgA in milk contribute to the protection of the neonatal pig against PEDV infections. Overall, the results of this experiment suggested that passively administered circulating antibodies contributed to the protection of neonatal piglets against PEDV infection.",2016 Apr 6,"['Poonsuk, Korakrit', 'Giménez-Lirola, Luis Gabriel', 'Zhang, Jianqiang', 'Arruda, Paolo', 'Chen, Qi', 'Correa da Silva Carrion, Lucas', 'Magtoto, Ronaldo', 'Pineyro, Pablo', 'Sarmento, Luciana', 'Wang, Chong', 'Sun, Yaxuan', 'Madson, Darin', 'Johnson, John', 'Yoon, Kyoung-Jin', 'Zimmerman, Jeffrey', 'Main, Rodger']",PLoS One,,,True
e87dc948912d7ec9174234037dec7c4369c5360c,PMC,Preparedness of healthcare workers at French Ebola referral centres,http://dx.doi.org/10.1016/j.nmni.2014.12.005,PMC4823472,27096101,CC BY,,2015 Feb 17,"['Tarantini, C.', 'Peretti-Watel, P.', 'Yazdanpana, Y.', 'Guery, B.', 'Chidiac, C.', 'Rapp, C.', 'Brouqui, P.']",New Microbes New Infect,,,False
105268027d44ab275991e358674462f77223e882,PMC,Complete Genome Sequence of the Porcine Epidemic Diarrhea Virus Strain SLO/JH-11/2015,http://dx.doi.org/10.1128/genomeA.01725-15,PMC4824273,27056240,CC BY,"Porcine epidemic diarrhea virus (PEDV) was detected for the first time in Slovenia in January 2015. The complete genome sequence of PEDV strain SLO/JH-11/2015, obtained from a fecal sample of a fattening pig with diarrhea in September 2015, is closely related to recently detected European strains.",2016 Apr 7,"['Toplak, Ivan', 'Ipavec, Manica', 'Kuhar, Urška', 'Kušar, Darja', 'Papić, Bojan', 'Koren, Simon', 'Toplak, Nataša']",Genome Announc,,,True
5d3e915d8571f298da4ff2e929d8475d68dc559f,PMC,Viruses Utilize Cellular Cues in Distinct Combination to Undergo Systematic Priming and Uncoating,http://dx.doi.org/10.1371/journal.ppat.1005467,PMC4824415,27055025,CC BY,,2016 Apr 7,"['Ravindran, Madhu Sudhan', 'Tsai, Billy']",PLoS Pathog,,,True
d0620683a194e739baca5c13917899ad7e5b2337,PMC,VIP: an integrated pipeline for metagenomics of virus identification and discovery,http://dx.doi.org/10.1038/srep23774,PMC4824449,27026381,CC BY,"Identification and discovery of viruses using next-generation sequencing technology is a fast-developing area with potential wide application in clinical diagnostics, public health monitoring and novel virus discovery. However, tremendous sequence data from NGS study has posed great challenge both in accuracy and velocity for application of NGS study. Here we describe VIP (“Virus Identification Pipeline”), a one-touch computational pipeline for virus identification and discovery from metagenomic NGS data. VIP performs the following steps to achieve its goal: (i) map and filter out background-related reads, (ii) extensive classification of reads on the basis of nucleotide and remote amino acid homology, (iii) multiple k-mer based de novo assembly and phylogenetic analysis to provide evolutionary insight. We validated the feasibility and veracity of this pipeline with sequencing results of various types of clinical samples and public datasets. VIP has also contributed to timely virus diagnosis (~10 min) in acutely ill patients, demonstrating its potential in the performance of unbiased NGS-based clinical studies with demand of short turnaround time. VIP is released under GPLv3 and is available for free download at: https://github.com/keylabivdc/VIP.",2016 Mar 30,"['Li, Yang', 'Wang, Hao', 'Nie, Kai', 'Zhang, Chen', 'Zhang, Yi', 'Wang, Ji', 'Niu, Peihua', 'Ma, Xuejun']",Sci Rep,,,True
aeba70238bd0c68d3995b9a241da7cb9d2bf73dc,PMC,VIP: an integrated pipeline for metagenomics of virus identification and discovery,http://dx.doi.org/10.1038/srep23774,PMC4824449,27026381,CC BY,"Identification and discovery of viruses using next-generation sequencing technology is a fast-developing area with potential wide application in clinical diagnostics, public health monitoring and novel virus discovery. However, tremendous sequence data from NGS study has posed great challenge both in accuracy and velocity for application of NGS study. Here we describe VIP (“Virus Identification Pipeline”), a one-touch computational pipeline for virus identification and discovery from metagenomic NGS data. VIP performs the following steps to achieve its goal: (i) map and filter out background-related reads, (ii) extensive classification of reads on the basis of nucleotide and remote amino acid homology, (iii) multiple k-mer based de novo assembly and phylogenetic analysis to provide evolutionary insight. We validated the feasibility and veracity of this pipeline with sequencing results of various types of clinical samples and public datasets. VIP has also contributed to timely virus diagnosis (~10 min) in acutely ill patients, demonstrating its potential in the performance of unbiased NGS-based clinical studies with demand of short turnaround time. VIP is released under GPLv3 and is available for free download at: https://github.com/keylabivdc/VIP.",2016 Mar 30,"['Li, Yang', 'Wang, Hao', 'Nie, Kai', 'Zhang, Chen', 'Zhang, Yi', 'Wang, Ji', 'Niu, Peihua', 'Ma, Xuejun']",Sci Rep,,,True
f6d409a4fff5c3c4d7d84cee872e80615e2027a4,PMC,Estimating risks of importation and local transmission of Zika virus infection,http://dx.doi.org/10.7717/peerj.1904,PMC4824915,27069825,CC BY,"Background. An international spread of Zika virus (ZIKV) infection has attracted global attention. ZIKV is conveyed by a mosquito vector, Aedes species, which also acts as the vector species of dengue and chikungunya viruses. Methods. Arrival time of ZIKV importation (i.e., the time at which the first imported case was diagnosed) in each imported country was collected from publicly available data sources. Employing a survival analysis model in which the hazard is an inverse function of the effective distance as informed by the airline transportation network data, and using dengue and chikungunya virus transmission data, risks of importation and local transmission were estimated. Results. A total of 78 countries with imported case(s) have been identified, with the arrival time ranging from 1 to 44 weeks since the first ZIKV was identified in Brazil, 2015. Whereas the risk of importation was well explained by the airline transportation network data, the risk of local transmission appeared to be best captured by additionally accounting for the presence of dengue and chikungunya viruses. Discussion. The risk of importation may be high given continued global travel of mildly infected travelers but, considering that the public health concerns over ZIKV infection stems from microcephaly, it is more important to focus on the risk of local and widespread transmission that could involve pregnant women. The predicted risk of local transmission was frequently seen in tropical and subtropical countries with dengue or chikungunya epidemic experience.",2016 Apr 5,"['Nah, Kyeongah', 'Mizumoto, Kenji', 'Miyamatsu, Yuichiro', 'Yasuda, Yohei', 'Kinoshita, Ryo', 'Nishiura, Hiroshi']",PeerJ,,,True
40ab93e7916aabc26190092d088a37d43b3240fc,PMC,"Participatory epidemiology at the neotropics: study of diseases of backyard livestock and description of hunting patterns in Uaxactún, Maya Reserve Biosphere, Guatemala",http://dx.doi.org/10.1186/s13104-016-2009-3,PMC4825071,27055652,CC BY,"BACKGROUND: The intention of the following study was to describe the interrelationship between villagers, domestic animals and wildlife at the Community Forestry Concession of Uaxactún, Guatemala by means of participatory epidemiological methods. The main focus was generating information regarding different livestock diseases considered important by villagers and their relevance, as well as obtaining knowledge concerning hunting activities and cooking methods to gain a better understanding of the interrelationship of people and animals and the diseases of their animals. RESULTS: For poultry, an overall prevalence of 41 % of Newcastle disease was found by means of the ELISA test by antibody detection, chicken being the most affected species in the village. No samples were positive to avian influenza with the HI test. No virus was isolated by means of the tracheal or cloaca swabbing of ducks. FOR HUNTING: All species could be hunted by chance at any time of the year. There was a difference in species hunted between seasons, peccaries being more frequently hunted during the dry season and in contrast, deer and wild avian during the rainy season. FOR COOKING: Villagers did not consume any raw meat. The cooking methods depended on the species. Stewing was the most favoured method for peccaries, wild birds, tepezcuintle and domestic poultry, whereas grilling was preferable for deer, roasting for armadillos and marinating for pork. CONCLUSION: According to the generated information, the most important domestic livestock species in the village are chickens and pigs, chickens being the most affected by diseases. No evident health problems on pigs were observed in this study. Hunting was shown as an activity enhanced by poverty and the lack of employment opportunities in the village and was mostly directed at larger species such as deer and peccaries. From the viewpoint of a transmission of zoonoses from animals to humans cooking methods mostly reflected a protective factor as no raw meat was eaten, stews and broths being the most common forms of cooking, involving an exposure of meat to high temperatures. Nonetheless, both agricultural and hunting activities represent a risk factor for the spread of diseases as hunters may act as mechanical vectors for different pathogens within domestic and wild animal populations.",2016 Apr 7,"['Mérida Ruíz, Samuel Alberto', 'Guerra Centeno, Dennis Sigfried', 'Bailey Leonardo, Edgar Leonel', 'Rohn, Karl', 'Kösters, Sarah', 'Kreienbrock, Lothar']",BMC Res Notes,,,True
11f2984bccfb6cb8952bceea9209357821a0583a,PMC,"Neglected Tropical Diseases in the Anthropocene: The Cases of Zika, Ebola, and Other Infections",http://dx.doi.org/10.1371/journal.pntd.0004648,PMC4825952,27058728,CC BY,,2016 Apr 8,"Hotez, Peter J.",PLoS Negl Trop Dis,,,True
90b97cb0a6ce9135c3a299462773ee94856ff22d,PMC,An eco-epidemiological study of Morbilli-related paramyxovirus infection in Madagascar bats reveals host-switching as the dominant macro-evolutionary mechanism,http://dx.doi.org/10.1038/srep23752,PMC4828640,27068130,CC BY,"An eco-epidemiological investigation was carried out on Madagascar bat communities to better understand the evolutionary mechanisms and environmental factors that affect virus transmission among bat species in closely related members of the genus Morbillivirus, currently referred to as Unclassified Morbilli-related paramyxoviruses (UMRVs). A total of 947 bats were investigated originating from 52 capture sites (22 caves, 18 buildings, and 12 outdoor sites) distributed over different bioclimatic zones of the island. Using RT-PCR targeting the L-polymerase gene of the Paramyxoviridae family, we found that 10.5% of sampled bats were infected, representing six out of seven families and 15 out of 31 species analyzed. Univariate analysis indicates that both abiotic and biotic factors may promote viral infection. Using generalized linear modeling of UMRV infection overlaid on biotic and abiotic variables, we demonstrate that sympatric occurrence of bats is a major factor for virus transmission. Phylogenetic analyses revealed that all paramyxoviruses infecting Malagasy bats are UMRVs and showed little host specificity. Analyses using the maximum parsimony reconciliation tool CoRe-PA, indicate that host-switching, rather than co-speciation, is the dominant macro-evolutionary mechanism of UMRVs among Malagasy bats.",2016 Apr 12,"['Mélade, Julien', 'Wieseke, Nicolas', 'Ramasindrazana, Beza', 'Flores, Olivier', 'Lagadec, Erwan', 'Gomard, Yann', 'Goodman, Steven M.', 'Dellagi, Koussay', 'Pascalis, Hervé']",Sci Rep,,,True
000b7d1517ceebb34e1e3e817695b6de03e2fa78,PMC,An eco-epidemiological study of Morbilli-related paramyxovirus infection in Madagascar bats reveals host-switching as the dominant macro-evolutionary mechanism,http://dx.doi.org/10.1038/srep23752,PMC4828640,27068130,CC BY,"An eco-epidemiological investigation was carried out on Madagascar bat communities to better understand the evolutionary mechanisms and environmental factors that affect virus transmission among bat species in closely related members of the genus Morbillivirus, currently referred to as Unclassified Morbilli-related paramyxoviruses (UMRVs). A total of 947 bats were investigated originating from 52 capture sites (22 caves, 18 buildings, and 12 outdoor sites) distributed over different bioclimatic zones of the island. Using RT-PCR targeting the L-polymerase gene of the Paramyxoviridae family, we found that 10.5% of sampled bats were infected, representing six out of seven families and 15 out of 31 species analyzed. Univariate analysis indicates that both abiotic and biotic factors may promote viral infection. Using generalized linear modeling of UMRV infection overlaid on biotic and abiotic variables, we demonstrate that sympatric occurrence of bats is a major factor for virus transmission. Phylogenetic analyses revealed that all paramyxoviruses infecting Malagasy bats are UMRVs and showed little host specificity. Analyses using the maximum parsimony reconciliation tool CoRe-PA, indicate that host-switching, rather than co-speciation, is the dominant macro-evolutionary mechanism of UMRVs among Malagasy bats.",2016 Apr 12,"['Mélade, Julien', 'Wieseke, Nicolas', 'Ramasindrazana, Beza', 'Flores, Olivier', 'Lagadec, Erwan', 'Gomard, Yann', 'Goodman, Steven M.', 'Dellagi, Koussay', 'Pascalis, Hervé']",Sci Rep,,,True
684dc6fccb8e9d754f09076c6a122bc0eead903f,PMC,Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection,http://dx.doi.org/10.1038/srep24179,PMC4828711,27067649,CC BY,"Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)(2) fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab′)(2) at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs.",2016 Apr 12,"['Zheng, Xuexing', 'Wong, Gary', 'Zhao, Yongkun', 'Wang, Hualei', 'He, Shihua', 'Bi, Yuhai', 'Chen, Weijin', 'Jin, Hongli', 'Gai, Weiwei', 'Chu, Di', 'Cao, Zengguo', 'Wang, Chong', 'Fan, Quanshui', 'Chi, Hang', 'Gao, Yuwei', 'Wang, Tiecheng', 'Feng, Na', 'Yan, Feihu', 'Huang, Geng', 'Zheng, Ying', 'Li, Nan', 'Li, Yuetao', 'Qian, Jun', 'Zou, Yong', 'Kobinger, Gary', 'Gao, George Fu', 'Qiu, Xiangguo', 'Yang, Songtao', 'Xia, Xianzhu']",Sci Rep,,,True
43c81e755add9b7f05c9a15f85c54dcd0d093b0b,PMC,Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection,http://dx.doi.org/10.1038/srep24179,PMC4828711,27067649,CC BY,"Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)(2) fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab′)(2) at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs.",2016 Apr 12,"['Zheng, Xuexing', 'Wong, Gary', 'Zhao, Yongkun', 'Wang, Hualei', 'He, Shihua', 'Bi, Yuhai', 'Chen, Weijin', 'Jin, Hongli', 'Gai, Weiwei', 'Chu, Di', 'Cao, Zengguo', 'Wang, Chong', 'Fan, Quanshui', 'Chi, Hang', 'Gao, Yuwei', 'Wang, Tiecheng', 'Feng, Na', 'Yan, Feihu', 'Huang, Geng', 'Zheng, Ying', 'Li, Nan', 'Li, Yuetao', 'Qian, Jun', 'Zou, Yong', 'Kobinger, Gary', 'Gao, George Fu', 'Qiu, Xiangguo', 'Yang, Songtao', 'Xia, Xianzhu']",Sci Rep,,,False
24fc42faaa7cf3f1b483806e77056a1d253715c5,PMC,An epidemiological study of rates of illness in passengers and crew at a busy Caribbean cruise port,http://dx.doi.org/10.1186/s12889-016-2991-3,PMC4828867,27067392,CC BY,"BACKGROUND: The Caribbean has one of the largest cruise ship industries in the world, with close to 20 million visitors per year. The potential for communicable disease outbreaks on vessels and the transmission by ship between countries is high. Barbados has one of the busiest ports in the Caribbean. Our aim was to describe and analyse the epidemiology of illnesses experienced by passengers and crew arriving at the Bridgetown Port, Barbados between 2009 and 2013. METHODS: Data on the illnesses recorded were extracted from the passenger and crew arrival registers and passenger and crew illness logs for all ships and maritime vessels arriving at Barbados’ Ports and passing through its territorial waters between January 2009 and December 2013. Data were entered into an Epi Info database and most of the analysis undertaken using Epi Info Version 7. Rates per 100,000 visits were calculated, and confidence intervals on these were derived using the software Openepi. RESULTS: There were 1031 cases of illness from over 3 million passenger visits and 1 million crew visits during this period. The overall event rate for communicable illnesses was 15.7 (95 % CI 14.4–17.1) per 100,000 passengers, and for crew was 24.0 (21.6–26.6) per 100, 000 crew. Gastroenteritis was the predominant illness experienced by passengers and crew followed by influenza. The event rate for gastroenteritis among passengers was 13.7 (12.5–15.0) per 100,000 and 14.4 (12.6, 16.5) for crew. The event rate for non-communicable illnesses was 3.4 per 100,000 passengers with myocardial infarction being the main diagnosis. The event rate for non-communicable illnesses among crew was 2.1 per 100,000, the leading cause being injuries. CONCLUSIONS: The predominant illnesses reported were gastroenteritis and influenza similar to previous published reports from around the world. This study is the first of its type in the Caribbean and the data provide a baseline for future surveillance and for comparison with other countries and regions.",2016 Apr 12,"['Marshall, Cathy Ann', 'Morris, Euclid', 'Unwin, Nigel']",BMC Public Health,,,True
85cd6377bbbcb026efd403df4177b5086df50d0d,PMC,Nosocomial infection control in healthcare settings: Protection against emerging infectious diseases,http://dx.doi.org/10.1186/s40249-016-0118-9,PMC4828876,27068809,CC BY,"The Middle East respiratory syndrome (MERS) outbreak in Korea in 2015 may be attributable to poor nosocomial infection control procedures implemented. Strict infection control measures were taken in the hospital where an imported case with MERS was treated in southern China and 53 health care workers were confirmed to be MERS-CoV negative. Infection control in healthcare settings, in which patients with emerging infectious diseases such as MERS, Ebola virus disease, and the severe acute respiratory syndrome (SARS) are diagnosed and treated, are often imperfect. When it comes to emerging or unknown infectious diseases, before the imported case was finally identified or community transmission was reported, cases have often occurred in clusters in healthcare settings. Nosocomial infection control measures should be further strengthened among the workers and inpatients in designated healthcare settings that accommodate suspected cases suffering from emerging or unknown infectious diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0118-9) contains supplementary material, which is available to authorized users.",2016 Apr 12,"['Fu, Chuanxi', 'Wang, Shengyong']",Infect Dis Poverty,,,False
ca6b85f95f1eca57c0601972938aa2b8878bc2f6,PMC,Nosocomial infection control in healthcare settings: Protection against emerging infectious diseases,http://dx.doi.org/10.1186/s40249-016-0118-9,PMC4828876,27068809,CC BY,"The Middle East respiratory syndrome (MERS) outbreak in Korea in 2015 may be attributable to poor nosocomial infection control procedures implemented. Strict infection control measures were taken in the hospital where an imported case with MERS was treated in southern China and 53 health care workers were confirmed to be MERS-CoV negative. Infection control in healthcare settings, in which patients with emerging infectious diseases such as MERS, Ebola virus disease, and the severe acute respiratory syndrome (SARS) are diagnosed and treated, are often imperfect. When it comes to emerging or unknown infectious diseases, before the imported case was finally identified or community transmission was reported, cases have often occurred in clusters in healthcare settings. Nosocomial infection control measures should be further strengthened among the workers and inpatients in designated healthcare settings that accommodate suspected cases suffering from emerging or unknown infectious diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0118-9) contains supplementary material, which is available to authorized users.",2016 Apr 12,"['Fu, Chuanxi', 'Wang, Shengyong']",Infect Dis Poverty,,,True
c5745c2eaaf8e94e31a179ce4e8775a3cd0e6745,PMC,Genetic Deletion of ACE2 Induces Vascular Dysfunction in C57BL/6 Mice: Role of Nitric Oxide Imbalance and Oxidative Stress,http://dx.doi.org/10.1371/journal.pone.0150255,PMC4829150,27070147,CC BY,"Accumulating evidence indicates that angiotensin-converting enzyme 2 (ACE2) plays a critical role in cardiovascular homeostasis, and its altered expression is associated with major cardiac and vascular disorders. The aim of this study was to evaluate the regulation of vascular function and assess the vascular redox balance in ACE2-deficient (ACE2(-/y)) animals. Experiments were performed in 20–22 week-old C57BL/6 and ACE2(-/y) male mice. Evaluation of endothelium-dependent and -independent relaxation revealed an impairment of in vitro and in vivo vascular function in ACE2(-/y) mice. Drastic reduction in eNOS expression at both protein and mRNA levels, and a decrease in (•)NO concentrations were observed in aortas of ACE2(-/y) mice in comparison to controls. Consistently, these mice presented a lower plasma and urine nitrite concentration, confirming reduced (•)NO availability in ACE2-deficient animals. Lipid peroxidation was significantly increased and superoxide dismutase activity was decreased in aorta homogenates of ACE2(-/y) mice, indicating impaired antioxidant capacity. Taken together, our data indicate, that ACE2 regulates vascular function by modulating nitric oxide release and oxidative stress. In conclusion, we elucidate mechanisms by which ACE2 is involved in the maintenance of vascular homeostasis. Furthermore, these findings provide insights into the role of the renin-angiotensin system in both vascular and systemic redox balance.",2016 Apr 12,"['Rabelo, Luiza A.', 'Todiras, Mihail', 'Nunes-Souza, Valéria', 'Qadri, Fatimunnisa', 'Szijártó, István András', 'Gollasch, Maik', 'Penninger, Josef M.', 'Bader, Michael', 'Santos, Robson A.', 'Alenina, Natalia']",PLoS One,,,True
9b6d81e0b5b4f49fcdf34be409406bc43988281e,PMC,Genetic Deletion of ACE2 Induces Vascular Dysfunction in C57BL/6 Mice: Role of Nitric Oxide Imbalance and Oxidative Stress,http://dx.doi.org/10.1371/journal.pone.0150255,PMC4829150,27070147,CC BY,"Accumulating evidence indicates that angiotensin-converting enzyme 2 (ACE2) plays a critical role in cardiovascular homeostasis, and its altered expression is associated with major cardiac and vascular disorders. The aim of this study was to evaluate the regulation of vascular function and assess the vascular redox balance in ACE2-deficient (ACE2(-/y)) animals. Experiments were performed in 20–22 week-old C57BL/6 and ACE2(-/y) male mice. Evaluation of endothelium-dependent and -independent relaxation revealed an impairment of in vitro and in vivo vascular function in ACE2(-/y) mice. Drastic reduction in eNOS expression at both protein and mRNA levels, and a decrease in (•)NO concentrations were observed in aortas of ACE2(-/y) mice in comparison to controls. Consistently, these mice presented a lower plasma and urine nitrite concentration, confirming reduced (•)NO availability in ACE2-deficient animals. Lipid peroxidation was significantly increased and superoxide dismutase activity was decreased in aorta homogenates of ACE2(-/y) mice, indicating impaired antioxidant capacity. Taken together, our data indicate, that ACE2 regulates vascular function by modulating nitric oxide release and oxidative stress. In conclusion, we elucidate mechanisms by which ACE2 is involved in the maintenance of vascular homeostasis. Furthermore, these findings provide insights into the role of the renin-angiotensin system in both vascular and systemic redox balance.",2016 Apr 12,"['Rabelo, Luiza A.', 'Todiras, Mihail', 'Nunes-Souza, Valéria', 'Qadri, Fatimunnisa', 'Szijártó, István András', 'Gollasch, Maik', 'Penninger, Josef M.', 'Bader, Michael', 'Santos, Robson A.', 'Alenina, Natalia']",PLoS One,,,False
66cda0b3d87b530e2659f8ac93a74ed963e9645e,PMC,Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids,http://dx.doi.org/10.1371/journal.pone.0153359,PMC4830604,27074005,CC BY,"Absolute, precise quantification methods expand the scope of nucleic acids research and have many practical applications. Digital polymerase chain reaction (dPCR) is a powerful method for nucleic acid detection and absolute quantification. However, it requires thermal cycling and accurate temperature control, which are difficult in resource-limited conditions. Accordingly, isothermal methods, such as recombinase polymerase amplification (RPA), are more attractive. We developed a picoliter well array (PWA) chip with 27,000 consistently sized picoliter reactions (314 pL) for isothermal DNA quantification using digital RPA (dRPA) at 39°C. Sample loading using a scraping liquid blade was simple, fast, and required small reagent volumes (i.e., <20 μL). Passivating the chip surface using a methoxy-PEG-silane agent effectively eliminated cross-contamination during dRPA. Our creative optical design enabled wide-field fluorescence imaging in situ and both end-point and real-time analyses of picoliter wells in a 6-cm(2) area. It was not necessary to use scan shooting and stitch serial small images together. Using this method, we quantified serial dilutions of a Listeria monocytogenes gDNA stock solution from 9 × 10(-1) to 4 × 10(-3) copies per well with an average error of less than 11% (N = 15). Overall dRPA-on-chip processing required less than 30 min, which was a 4-fold decrease compared to dPCR, requiring approximately 2 h. dRPA on the PWA chip provides a simple and highly sensitive method to quantify nucleic acids without thermal cycling or precise micropump/microvalve control. It has applications in fast field analysis and critical clinical diagnostics under resource-limited settings.",2016 Apr 13,"['Li, Zhao', 'Liu, Yong', 'Wei, Qingquan', 'Liu, Yuanjie', 'Liu, Wenwen', 'Zhang, Xuelian', 'Yu, Yude']",PLoS One,,,True
450811c073efd4b4b2140c1ce4ad035e58ee834c,PMC,Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids,http://dx.doi.org/10.1371/journal.pone.0153359,PMC4830604,27074005,CC BY,"Absolute, precise quantification methods expand the scope of nucleic acids research and have many practical applications. Digital polymerase chain reaction (dPCR) is a powerful method for nucleic acid detection and absolute quantification. However, it requires thermal cycling and accurate temperature control, which are difficult in resource-limited conditions. Accordingly, isothermal methods, such as recombinase polymerase amplification (RPA), are more attractive. We developed a picoliter well array (PWA) chip with 27,000 consistently sized picoliter reactions (314 pL) for isothermal DNA quantification using digital RPA (dRPA) at 39°C. Sample loading using a scraping liquid blade was simple, fast, and required small reagent volumes (i.e., <20 μL). Passivating the chip surface using a methoxy-PEG-silane agent effectively eliminated cross-contamination during dRPA. Our creative optical design enabled wide-field fluorescence imaging in situ and both end-point and real-time analyses of picoliter wells in a 6-cm(2) area. It was not necessary to use scan shooting and stitch serial small images together. Using this method, we quantified serial dilutions of a Listeria monocytogenes gDNA stock solution from 9 × 10(-1) to 4 × 10(-3) copies per well with an average error of less than 11% (N = 15). Overall dRPA-on-chip processing required less than 30 min, which was a 4-fold decrease compared to dPCR, requiring approximately 2 h. dRPA on the PWA chip provides a simple and highly sensitive method to quantify nucleic acids without thermal cycling or precise micropump/microvalve control. It has applications in fast field analysis and critical clinical diagnostics under resource-limited settings.",2016 Apr 13,"['Li, Zhao', 'Liu, Yong', 'Wei, Qingquan', 'Liu, Yuanjie', 'Liu, Wenwen', 'Zhang, Xuelian', 'Yu, Yude']",PLoS One,,,False
953d3fece0d805133c1e9a3f02a3f0711dab6161,PMC,Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids,http://dx.doi.org/10.1371/journal.pone.0153359,PMC4830604,27074005,CC BY,"Absolute, precise quantification methods expand the scope of nucleic acids research and have many practical applications. Digital polymerase chain reaction (dPCR) is a powerful method for nucleic acid detection and absolute quantification. However, it requires thermal cycling and accurate temperature control, which are difficult in resource-limited conditions. Accordingly, isothermal methods, such as recombinase polymerase amplification (RPA), are more attractive. We developed a picoliter well array (PWA) chip with 27,000 consistently sized picoliter reactions (314 pL) for isothermal DNA quantification using digital RPA (dRPA) at 39°C. Sample loading using a scraping liquid blade was simple, fast, and required small reagent volumes (i.e., <20 μL). Passivating the chip surface using a methoxy-PEG-silane agent effectively eliminated cross-contamination during dRPA. Our creative optical design enabled wide-field fluorescence imaging in situ and both end-point and real-time analyses of picoliter wells in a 6-cm(2) area. It was not necessary to use scan shooting and stitch serial small images together. Using this method, we quantified serial dilutions of a Listeria monocytogenes gDNA stock solution from 9 × 10(-1) to 4 × 10(-3) copies per well with an average error of less than 11% (N = 15). Overall dRPA-on-chip processing required less than 30 min, which was a 4-fold decrease compared to dPCR, requiring approximately 2 h. dRPA on the PWA chip provides a simple and highly sensitive method to quantify nucleic acids without thermal cycling or precise micropump/microvalve control. It has applications in fast field analysis and critical clinical diagnostics under resource-limited settings.",2016 Apr 13,"['Li, Zhao', 'Liu, Yong', 'Wei, Qingquan', 'Liu, Yuanjie', 'Liu, Wenwen', 'Zhang, Xuelian', 'Yu, Yude']",PLoS One,,,False
7fddc064e4c4aac26961aa413f27193ad175095b,PMC,"International Air Travel to Ohio, USA, and the Impact on Malaria, Influenza, and Hepatitis A",http://dx.doi.org/10.1155/2016/8258946,PMC4830737,27123365,CC BY,"The State of Ohio led the United States in measles in 2014, ostensibly related to international air travel (IAT), and ranked lower than 43 other states in infectious disease outbreak preparedness. We conducted a retrospective cohort study using surveillance data of the total Ohio population of 11 million from 2010 through 2014 with a nested case control of air travelers to determine the risk of malaria, seasonal influenza hospitalizations (IH), and hepatitis A (HA) disease related to international travel and to estimate the association with domestic enplanement. IAT appeared protective for HA and IH with a risk of 0.031 (.02–.04) but for malaria was 2.7 (2.07–3.62). Enplanement increased the risk for nonendemic M 3.5 (2.5–4.9) and for HA and IH 1.39 (1.34–1.44). IAT's ratio of relative risk (RRR) of malaria to HA and IH was 87.1 (55.8–136) greater than 219 times versus domestic enplanement which was protective for malaria at 0.397 (0.282–0.559). Malaria is correlated with IAT with cases increasing by 6.9 for every 10,000 passports issued.",2016 Mar 31,"['Brannen, Donald E.', 'Alhammad, Ali', 'Branum, Melissa', 'Schmitt, Amy']",Scientifica (Cairo),,,True
57b8e034f902f2883dbbafaeef554cb2deb64963,PMC,Silver Nanoparticles Induce HePG-2 Cells Apoptosis Through ROS-Mediated Signaling Pathways,http://dx.doi.org/10.1186/s11671-016-1419-4,PMC4830774,27075340,CC BY,"Recently, silver nanoparticles (AgNPs) have been shown to provide a novel approach to overcome tumors, especially those of hepatocarcinoma. However, the anticancer mechanism of silver nanoparticles is unclear. Thus, the purpose of this study was to estimate the effect of AgNPs on proliferation and activation of ROS-mediated signaling pathway on human hepatocellular carcinoma HePG-2 cells. A simple chemical method for preparing AgNPs with superior anticancer activity has been showed in this study. AgNPs were detected by transmission electronic microscopy (TEM) and energy dispersive X-ray (EDX). The size distribution and zeta potential of silver nanoparticles were detected by Zetasizer Nano. The average size of AgNPs (2 nm) observably increased the cellular uptake by endocytosis. AgNPs markedly inhibited the proliferation of HePG-2 cells through induction of apoptosis with caspase-3 activation and PARP cleavage. AgNPs with dose-dependent manner significantly increased the apoptotic cell population (sub-G1). Furthermore, AgNP-induced apoptosis was found dependent on the overproduction of reactive oxygen species (ROS) and affecting of MAPKs and AKT signaling and DNA damage-mediated p53 phosphorylation to advance HePG-2 cells apoptosis. Therefore, our results show that the mechanism of ROS-mediated signaling pathways may provide useful information in AgNP-induced HePG-2 cell apoptosis.",2016 Apr 14,"['Zhu, Bing', 'Li, Yinghua', 'Lin, Zhengfang', 'Zhao, Mingqi', 'Xu, Tiantian', 'Wang, Changbing', 'Deng, Ning']",Nanoscale Res Lett,,,True
f87fb7ecfabe0bae476e587f8c5eb01b15b24db0,PMC,Finite Element Analysis on Nanomechanical Detection of Small Particles: Toward Virus Detection,http://dx.doi.org/10.3389/fmicb.2016.00488,PMC4830830,27148181,CC BY,"Detection of small particles, including viruses and particulate matter (PM), has been attracting much attention in light of increasing need for environmental monitoring. Owing to their high versatility, a nanomechanical sensor is one of the most promising sensors which can be adapted to various monitoring systems. In this study, we present an optimization strategy to efficiently detect small particles with nanomechanical sensors. Adsorption of particles on the receptor layer of nanomechanical sensors and the resultant signal are analyzed using finite element analysis (FEA). We investigate the effect of structural parameters (e.g., adsorption position and embedded depth of a particle and thickness of the receptor layer) and elastic properties of the receptor layer (e.g., Young's modulus and Poisson's ratio) on the sensitivity. It is found that a membrane-type surface stress sensors (MSS) has the potential for robust detection of small particles.",2016 Apr 14,"['Imamura, Gaku', 'Shiba, Kota', 'Yoshikawa, Genki']",Front Microbiol,,,True
fe58b17bca43d017cf1af9b5748147b25f067b7d,PMC,The Use of Kosher Phenotyping for Mapping QTL Affecting Susceptibility to Bovine Respiratory Disease,http://dx.doi.org/10.1371/journal.pone.0153423,PMC4831767,27077383,CC BY,"Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in feedlot cattle, caused by multiple pathogens that become more virulent in response to stress. As clinical signs often go undetected and various preventive strategies failed, identification of genes affecting BRD is essential for selection for resistance. Selective DNA pooling (SDP) was applied in a genome wide association study (GWAS) to map BRD QTLs in Israeli Holstein male calves. Kosher scoring of lung adhesions was used to allocate 122 and 62 animals to High (Glatt Kosher) and Low (Non-Kosher) resistant groups, respectively. Genotyping was performed using the Illumina BovineHD BeadChip according to the Infinium protocol. Moving average of -logP was used to map QTLs and Log drop was used to define their boundaries (QTLRs). The combined procedure was efficient for high resolution mapping. Nineteen QTLRs distributed over 13 autosomes were found, some overlapping previous studies. The QTLRs contain polymorphic functional and expression candidate genes to affect kosher status, with putative immunological and wound healing activities. Kosher phenotyping was shown to be a reliable means to map QTLs affecting BRD morbidity.",2016 Apr 14,"['Lipkin, Ehud', 'Strillacci, Maria Giuseppina', 'Eitam, Harel', 'Yishay, Moran', 'Schiavini, Fausta', 'Soller, Morris', 'Bagnato, Alessandro', 'Shabtay, Ariel']",PLoS One,,,True
1ce05f10fab075f30d07b091fcc8530aa0b6b252,PMC,The Use of Kosher Phenotyping for Mapping QTL Affecting Susceptibility to Bovine Respiratory Disease,http://dx.doi.org/10.1371/journal.pone.0153423,PMC4831767,27077383,CC BY,"Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in feedlot cattle, caused by multiple pathogens that become more virulent in response to stress. As clinical signs often go undetected and various preventive strategies failed, identification of genes affecting BRD is essential for selection for resistance. Selective DNA pooling (SDP) was applied in a genome wide association study (GWAS) to map BRD QTLs in Israeli Holstein male calves. Kosher scoring of lung adhesions was used to allocate 122 and 62 animals to High (Glatt Kosher) and Low (Non-Kosher) resistant groups, respectively. Genotyping was performed using the Illumina BovineHD BeadChip according to the Infinium protocol. Moving average of -logP was used to map QTLs and Log drop was used to define their boundaries (QTLRs). The combined procedure was efficient for high resolution mapping. Nineteen QTLRs distributed over 13 autosomes were found, some overlapping previous studies. The QTLRs contain polymorphic functional and expression candidate genes to affect kosher status, with putative immunological and wound healing activities. Kosher phenotyping was shown to be a reliable means to map QTLs affecting BRD morbidity.",2016 Apr 14,"['Lipkin, Ehud', 'Strillacci, Maria Giuseppina', 'Eitam, Harel', 'Yishay, Moran', 'Schiavini, Fausta', 'Soller, Morris', 'Bagnato, Alessandro', 'Shabtay, Ariel']",PLoS One,,,False
1e71a51670cdda3d92a1f182967d78dca3bb5d44,PMC,Retinoic acid facilitates inactivated transmissible gastroenteritis virus induction of CD8(+) T-cell migration to the porcine gut,http://dx.doi.org/10.1038/srep24152,PMC4832189,27080036,CC BY,"The digestive tract is the entry site for transmissible gastroenteritis virus (TGEV). TGEV transmission can be prevented if local immunity is established with increased lymphocytes. The current parenteral mode of vaccination stimulates systemic immunity well, but it does not induce sufficient mucosal immunity. Retinoic acid (RA) plays an important role in the induction of cells that imprint gut-homing molecules. We examined whether RA assist parenteral vaccination of pigs could improve mucosal immunity. We demonstrated that elevated numbers of gut-homing CD8(+) T cells (which express α4β7 and CCR9 molecules) were presented in porcine inguinal lymph nodes and were recruited to the small intestine by RA. Intestinal mucosal immunity (IgA titre) and systemic immunity (serum IgG titre) were enhanced by RA. Therefore, we hypothesized that RA could induce DCs to form an immature mucosal phenotype and could recruit them to the small intestinal submucosa. Porcine T-cells expressed β7 integrin and CCR9 receptors and migrated to CCL25 by a mechanism that was dependent of activation by RA-pretreated DCs, rather than direct activation by RA. Together, our results provide powerful evidence that RA can assist whole inactivated TGEV (WI-TGEV) via subcutaneous (s.c.) immunization to generate intestinal immunity, and offer new vaccination strategies against TGEV.",2016 Apr 15,"['Chen, Xiaojuan', 'Tu, Chongzhi', 'Qin, Tao', 'Zhu, Liqi', 'Yin, Yinyan', 'Yang, Qian']",Sci Rep,,,True
4ccdf68a98517afb602bd6ab2eca8e77fac05830,PMC,Reverse Transcription Cross-Priming Amplification–Nucleic Acid Test Strip for Rapid Detection of Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.1038/srep24702,PMC4835727,27090105,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a highly transmissible coronavirus that causes a severe enteric disease particularly in neonatal piglets. In this study, a rapid method for detecting PEDV was developed based on cross-priming amplification and nucleic acid test strip(CPA-NATS). Five primers specific for the N gene sequence of PEDV were used for the cross-priming amplification. Detection of amplification products based on labeled probe primers was conducted with strip binding antibody of labeled markers. The CPA method was evaluated and compared with a PCR method. The reverse transcription CPA system was further optimized for detecting PEDV RNA in clinical specimens. Results showed that the method was highly specific for the detection of PEDV, and had the same sensitivity as PCR, with detection limit of 10(−6) diluted plasmid containing the target gene of PEDV. It was also successfully applied to detecting PEDV in clinical specimens. The reverse transcription CPA-NATS detection system established in this study offers a specific, sensitive, rapid, and simple detection tool for screening PEDV, which can contribute to strategies in the effective control of PEDV in swine.",2016 Apr 19,"['Wang, Feng-Xue', 'Yuan, Dan-Yi', 'Jin, Ya-Nan', 'Hu, Lin', 'Sun, Zhi-Yong', 'He, Qian', 'Zhao, Shi-Hua', 'Zhan, Shu-Bai', 'Wen, Yong-Jun']",Sci Rep,,,True
213fdedff656134ff3dbe24a7d7bbba61d13baa1,PMC,"Blockage of indoleamine 2,3-dioxygenase regulates Japanese encephalitis via enhancement of type I/II IFN innate and adaptive T-cell responses",http://dx.doi.org/10.1186/s12974-016-0551-5,PMC4835894,27090635,CC BY,"BACKGROUND: Japanese encephalitis (JE), a leading cause of viral encephalitis, is characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV). Indoleamine 2,3-dioxygenase (IDO) has been identified as an enzyme associated with immunoregulatory function. Although the regulatory role of IDO in viral replication has been postulated, the in vivo role of IDO activity has not been fully addressed in neurotropic virus-caused encephalitis. METHODS: Mice in which IDO activity was inhibited by genetic ablation or using a specific inhibitor were examined for mortality and clinical signs after infection. Neuroinflammation was evaluated by central nervous system (CNS) infiltration of leukocytes and cytokine expression. IDO expression, viral burden, JEV-specific T-cell, and type I/II interferon (IFN-I/II) innate responses were also analyzed. RESULTS: Elevated expression of IDO activity in myeloid and neuron cells of the lymphoid and CNS tissues was closely associated with clinical signs of JE. Furthermore, inhibition of IDO activity enhanced resistance to JE, reduced the viral burden in lymphoid and CNS tissues, and resulted in early and increased CNS infiltration by Ly-6C(hi) monocytes, NK, CD4(+), and CD8(+) T-cells. JE amelioration in IDO-ablated mice was also associated with enhanced NK and JEV-specific T-cell responses. More interestingly, IDO ablation induced rapid enhancement of type I IFN (IFN-I) innate responses in CD11c(+) dendritic cells (DCs), including conventional and plasmacytoid DCs, following JEV infection. This enhanced IFN-I innate response in IDO-ablated CD11c(+) DCs was coupled with strong induction of PRRs (RIG-I, MDA5), transcription factors (IRF7, STAT1), and antiviral ISG genes (Mx1, Mx2, ISG49, ISG54, ISG56). IDO ablation also enhanced the IFN-I innate response in neuron cells, which may delay the spread of virus in the CNS. Finally, we identified that IDO ablation in myeloid cells derived from hematopoietic stem cells (HSCs) dominantly contributed to JE amelioration and that HSC-derived leukocytes played a key role in the enhanced IFN-I innate responses in the IDO-ablated environment. CONCLUSIONS: Inhibition of IDO activity ameliorated JE via enhancement of antiviral IFN-I/II innate and adaptive T-cell responses and increased CNS infiltration of peripheral leukocytes. Therefore, our data provide valuable insight into the use of IDO inhibition by specific inhibitors as a promising tool for therapeutic and prophylactic strategies against viral encephalitis caused by neurotropic viruses.",2016 Apr 18,"['Kim, Seong Bum', 'Choi, Jin Young', 'Uyangaa, Erdenebileg', 'Patil, Ajit Mahadev', 'Hossain, Ferdaus Mohd Altaf', 'Hur, Jin', 'Park, Sang-Youel', 'Lee, John-Hwa', 'Kim, Koanhoi', 'Eo, Seong Kug']",J Neuroinflammation,,,True
4c1e7d31ff353e605f4211eebae16eaea9defed6,PMC,A Dimerization-Dependent Mechanism Drives the Endoribonuclease Function of Porcine Reproductive and Respiratory Syndrome Virus nsp11,http://dx.doi.org/10.1128/JVI.03065-15,PMC4836315,26912626,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) RNA endoribonuclease nsp11 belongs to the XendoU superfamily and plays a crucial role in arterivirus replication. Here, we report the first crystal structure of the arterivirus nsp11 protein from PRRSV, which exhibits a unique structure and assembles into an asymmetric dimer whose structure is completely different from the hexameric structure of coronavirus nsp15. However, the structures of the PRRSV nsp11 and coronavirus nsp15 catalytic domains were perfectly superimposed, especially in the “active site loop” (His129 to His144) and “supporting loop” (Val162 to Thr179) regions. Importantly, our biochemical data demonstrated that PRRSV nsp11 exists mainly as a dimer in solution. Mutations of the major dimerization site determinants (Ser74 and Phe76) in the dimerization interface destabilized the dimer in solution and severely diminished endoribonuclease activity, indicating that the dimer is the biologically functional unit. In the dimeric structure, the active site loop and supporting loop are packed against one another and stabilized by monomer-monomer interactions. These findings may help elucidate the mechanism underlying arterivirus replication and may represent great potential for the development of antiviral drugs. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) is a member of the family Arteriviridae, order Nidovirales. PRRSV is a major agent of respiratory diseases in pigs, causing tremendous economic losses to the swine industry worldwide. The PRRSV nsp11 endoribonuclease plays a vital role in arterivirus replication, but its precise roles and mechanisms of action are poorly understood. Here, we report the first dimeric structure of the arterivirus nsp11 from PRRSV at 2.75-Å resolution. Structural and biochemical experiments demonstrated that nsp11 exists mainly as a dimer in solution and that nsp11 may be fully active as a dimer. Mutagenesis and structural analysis revealed NendoU active site residues, which are conserved throughout the order Nidovirales (families Arteriviridae and Coronaviridae) and the major determinants of dimerization (Ser74 and Phe76) in Arteriviridae. Importantly, these findings may provide a new structural basis for antiviral drug development.",2016 Apr 14,"['Shi, Yuejun', 'Li, Youwen', 'Lei, Yingying', 'Ye, Gang', 'Shen, Zhou', 'Sun, Limeng', 'Luo, Rui', 'Wang, Dang', 'Fu, Zhen F.', 'Xiao, Shaobo', 'Peng, Guiqing']",J Virol,,,True
1bab633e4d3ab1ed30599369e8654c235256c5cd,PMC,The Proteolytic Activation of (H3N2) Influenza A Virus Hemagglutinin Is Facilitated by Different Type II Transmembrane Serine Proteases,http://dx.doi.org/10.1128/JVI.02693-15,PMC4836353,26889029,CC BY,"Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is necessary for viral activation and infectivity. In humans and mice, members of the type II transmembrane protease family (TTSP), e.g., TMPRSS2, TMPRSS4, and TMPRSS11d (HAT), have been shown to cleave influenza virus HA for viral activation and infectivity in vitro. Recently, we reported that inactivation of a single HA-activating protease gene, Tmprss2, in knockout mice inhibits the spread of H1N1 influenza viruses. However, after infection of Tmprss2 knockout mice with an H3N2 influenza virus, only a slight increase in survival was observed, and mice still lost body weight. In this study, we investigated an additional trypsin-like protease, TMPRSS4. Both TMPRSS2 and TMPRSS4 are expressed in the same cell types of the mouse lung. Deletion of Tmprss4 alone in knockout mice does not protect them from body weight loss and death upon infection with H3N2 influenza virus. In contrast, Tmprss2(−/−) Tmprss4(−/−) double-knockout mice showed a remarkably reduced virus spread and lung pathology, in addition to reduced body weight loss and mortality. Thus, our results identified TMPRSS4 as a second host cell protease that, in addition to TMPRSS2, is able to activate the HA of H3N2 influenza virus in vivo. IMPORTANCE Influenza epidemics and recurring pandemics are responsible for significant global morbidity and mortality. Due to high variability of the virus genome, resistance to available antiviral drugs is frequently observed, and new targets for treatment of influenza are needed. Host cell factors essential for processing of the virus hemagglutinin represent very suitable drug targets because the virus is dependent on these host factors for replication. We reported previously that Tmprss2-deficient mice are protected against H1N1 virus infections, but only marginal protection against H3N2 virus infections was observed. Here we show that deletion of two host protease genes, Tmprss2 and Tmprss4, strongly reduced viral spread as well as lung pathology and resulted in increased survival after H3N2 virus infection. Thus, TMPRSS4 represents another host cell factor that is involved in cleavage activation of H3N2 influenza viruses in vivo.",2016 Apr 14,"['Kühn, Nora', 'Bergmann, Silke', 'Kösterke, Nadine', 'Lambertz, Ruth L. O.', 'Keppner, Anna', 'van den Brand, Judith M. A.', 'Pöhlmann, Stefan', 'Weiß, Siegfried', 'Hummler, Edith', 'Hatesuer, Bastian', 'Schughart, Klaus']",J Virol,,,True
381bb3c674e68a97e38efe5d6f9952c7a64522d3,PMC,Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs,http://dx.doi.org/10.1371/journal.pone.0151922,PMC4836704,27093541,CC BY,"Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV). Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2) chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.",2016 Apr 19,"['Hiremath, Jagadish', 'Kang, Kyung-il', 'Xia, Ming', 'Elaish, Mohamed', 'Binjawadagi, Basavaraj', 'Ouyang, Kang', 'Dhakal, Santosh', 'Arcos, Jesus', 'Torrelles, Jordi B.', 'Jiang, X.', 'Lee, Chang Won', 'Renukaradhya, Gourapura J.']",PLoS One,,,True
2b2b4954a960745a09009e9de6d1cb87358bfa6a,PMC,Development of Monoclonal Antibody and Diagnostic Test for Middle East Respiratory Syndrome Coronavirus Using Cell-Free Synthesized Nucleocapsid Antigen,http://dx.doi.org/10.3389/fmicb.2016.00509,PMC4837155,27148198,CC BY,"Protein nativity is one of the most critical factors for the quality of antigens used as immunogens and the reactivities of the resultant antibodies. The preparation and purification of native viral antigens in conventional cell-based protein expression systems are often accompanied by technical hardships. These challenges are attributable mainly to protein aggregation and insolubility during expression and purification, as well as to very low expression levels associated with the toxicity of some viral proteins. Here, we describe a novel approach for the production of monoclonal antibodies (mAbs) against nucleocapsid protein (NP) of the Middle East respiratory syndrome coronavirus (MERS-CoV). Using a wheat germ cell-free protein synthesis system, we successfully prepared large amounts of MERS-CoV NP antigen in a state that was highly soluble and intact for immunization. Following mouse immunization and hybridoma generation, we selected seven hybridoma clones that produced mAbs with exclusive reactivity against MERS-CoV NP. Epitope mapping and subsequent bioinformatic analysis revealed that these mAbs recognized epitopes located within relatively highly conserved regions of the MERS-CoV amino-acid sequence. Consistently, the mAbs exhibited no obvious cross-reactivity with NPs derived from other related viruses, including SARS coronavirus. After determining the optimal combinations of these mAbs, we developed an enzyme-linked immunosorbent assay and a rapid immunochromatographic antigen detection test that can be reliably used for laboratory diagnosis of MERS-CoV. Thus, this study provides strong evidence that the wheat germ cell-free system is useful for the production of diagnostic mAbs against emerging pathogens.",2016 Apr 20,"['Yamaoka, Yutaro', 'Matsuyama, Shutoku', 'Fukushi, Shuetsu', 'Matsunaga, Satoko', 'Matsushima, Yuki', 'Kuroyama, Hiroyuki', 'Kimura, Hirokazu', 'Takeda, Makoto', 'Chimuro, Tomoyuki', 'Ryo, Akihide']",Front Microbiol,,,True
a413230495919e899e941fe5c2993c7cec504d4a,PMC,Structural characterization of recombinant IAV polymerase reveals a stable complex between viral PA-PB1 heterodimer and host RanBP5,http://dx.doi.org/10.1038/srep24727,PMC4837377,27095520,CC BY,"The genome of influenza A virus (IAV) comprises eight RNA segments (vRNA) which are transcribed and replicated by the heterotrimeric IAV RNA-dependent RNA-polymerase (RdRp). RdRp consists of three subunits (PA, PB1 and PB2) and binds both the highly conserved 3′- and 5′-ends of the vRNA segment. The IAV RdRp is an important antiviral target, but its structural mechanism has remained largely elusive to date. By applying a polyprotein strategy, we produced RdRp complexes and define a minimal human IAV RdRp core complex. We show that PA-PB1 forms a stable heterodimeric submodule that can strongly interact with 5′-vRNA. In contrast, 3′-vRNA recognition critically depends on the PB2 N-terminal domain. Moreover, we demonstrate that PA-PB1 forms a stable and stoichiometric complex with host nuclear import factor RanBP5 that can be modelled using SAXS and we show that the PA-PB1-RanPB5 complex is no longer capable of 5′-vRNA binding. Our results provide further evidence for a step-wise assembly of IAV structural components, regulated by nuclear transport mechanisms and host factor binding.",2016 Apr 20,"['Swale, Christopher', 'Monod, Alexandre', 'Tengo, Laura', 'Labaronne, Alice', 'Garzoni, Frédéric', 'Bourhis, Jean-Marie', 'Cusack, Stephen', 'Schoehn, Guy', 'Berger, Imre', 'Ruigrok, Rob WH', 'Crépin, Thibaut']",Sci Rep,,,True
8cd08e9912baa6d4b3d41a42d02951c098044045,PMC,Structural characterization of recombinant IAV polymerase reveals a stable complex between viral PA-PB1 heterodimer and host RanBP5,http://dx.doi.org/10.1038/srep24727,PMC4837377,27095520,CC BY,"The genome of influenza A virus (IAV) comprises eight RNA segments (vRNA) which are transcribed and replicated by the heterotrimeric IAV RNA-dependent RNA-polymerase (RdRp). RdRp consists of three subunits (PA, PB1 and PB2) and binds both the highly conserved 3′- and 5′-ends of the vRNA segment. The IAV RdRp is an important antiviral target, but its structural mechanism has remained largely elusive to date. By applying a polyprotein strategy, we produced RdRp complexes and define a minimal human IAV RdRp core complex. We show that PA-PB1 forms a stable heterodimeric submodule that can strongly interact with 5′-vRNA. In contrast, 3′-vRNA recognition critically depends on the PB2 N-terminal domain. Moreover, we demonstrate that PA-PB1 forms a stable and stoichiometric complex with host nuclear import factor RanBP5 that can be modelled using SAXS and we show that the PA-PB1-RanPB5 complex is no longer capable of 5′-vRNA binding. Our results provide further evidence for a step-wise assembly of IAV structural components, regulated by nuclear transport mechanisms and host factor binding.",2016 Apr 20,"['Swale, Christopher', 'Monod, Alexandre', 'Tengo, Laura', 'Labaronne, Alice', 'Garzoni, Frédéric', 'Bourhis, Jean-Marie', 'Cusack, Stephen', 'Schoehn, Guy', 'Berger, Imre', 'Ruigrok, Rob WH', 'Crépin, Thibaut']",Sci Rep,,,False
78057e9db3bebe6ecfc99fbc036414ebd4115cfd,PMC,Diminished COX-2/PGE(2)-Mediated Antiviral Response Due to Impaired NOX/MAPK Signaling in G6PD-Knockdown Lung Epithelial Cells,http://dx.doi.org/10.1371/journal.pone.0153462,PMC4838297,27097228,CC BY,"Glucose-6-phosphate dehydrogenase (G6PD) provides the reducing agent NADPH to meet the cellular needs for reductive biosynthesis and the maintenance of redox homeostasis. G6PD-deficient cells experience a high level of oxidative stress and an increased susceptibility to viral infections. Cyclooxygenase-2 (COX-2) is a key mediator in the regulation of viral replication and inflammatory response. In the current study, the role of G6PD on the inflammatory response was determined in both scramble control and G6PD-knockdown (G6PD-kd) A549 cells upon tumor necrosis factor-α (TNF-α) stimulation. A decreased expression pattern of induced COX-2 and reduced production of downstream PGE(2) occurred upon TNF-α stimulation in G6PD-kd A549 cells compared with scramble control A549 cells. TNF-α-induced antiviral activity revealed that decreased COX-2 expression enhanced the susceptibility to coronavirus 229E infection in G6PD-kd A549 cells and was a result of the decreased phosphorylation levels of MAPK (p38 and ERK1/2) and NF-κB. The impaired inflammatory response in G6PD-kd A549 cells was found to be mediated through NADPH oxidase (NOX) signaling as elucidated by cell pretreatment with a NOX2-siRNA or NOX inhibitor, diphenyleneiodonium chloride (DPI). In addition, NOX activity with TNF-α treatment in G6PD-kd A549 cells was not up-regulated and was coupled with a decrease in NOX subunit expression at the transcriptional level, implying that TNF-α-mediated NOX signaling requires the participation of G6PD. Together, these data suggest that G6PD deficiency affects the cellular inflammatory response and the decreased TNF-α-mediated antiviral response in G6PD-kd A549 cells is a result of dysregulated NOX/MAPK/NF-κB/COX-2 signaling.",2016 Apr 20,"['Lin, Hsin-Ru', 'Wu, Yi-Hsuan', 'Yen, Wei-Chen', 'Yang, Chuen-Mao', 'Chiu, Daniel Tsun-Yee']",PLoS One,,,True
058b0cc7cecd43d80ed47196cb5376fa10efb58a,PMC,Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?,http://dx.doi.org/10.1371/journal.pone.0152481,PMC4838299,27096199,CC BY,"BACKGROUND: Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. OBJECTIVES: To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). METHODS: We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. RESULTS: 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. CONCLUSION: The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role.",2016 Apr 20,"['Cebey-López, Miriam', 'Herberg, Jethro', 'Pardo-Seco, Jacobo', 'Gómez-Carballa, Alberto', 'Martinón-Torres, Nazareth', 'Salas, Antonio', 'Martinón-Sánchez, José María', 'Justicia, Antonio', 'Rivero-Calle, Irene', 'Sumner, Edward', 'Fink, Colin', 'Martinón-Torres, Federico', None]",PLoS One,,,True
dd2a154b5fe59f997e47913b3a6da5d23bdb7556,PMC,Resveratrol enhances HBV replication through activating Sirt1-PGC-1α-PPARα pathway,http://dx.doi.org/10.1038/srep24744,PMC4838842,27098390,CC BY,"The population of hepatitis B combined with a number of metabolic disorders is increasing significantly. Resveratrol (RSV) has been used as a preclinical drug for the treatment of the metabolic disorders. However, the impact of RSV on HBV replication remains unknown. In this study, the HBV-expressing hepatocelluar carcinoma cell line and mouse model created by hydrodynamic injection of viral DNA were used. We found that RSV activates Sirt1, which in turn deacetylates PGC-1α and subsequently increases the transcriptional activity of PPARα, leading to the enhanced HBV transcription and replication in vitro and in vivo. In addition, we found that this pathway is also required for fasting-induced HBV transcription. Taken together, this study identifies that RSV enhances HBV transcription and replication especially acting on the core promoter, which depends on Sirt1-PGC-1α-PPARα pathway. We conclude that RSV may exacerbate the progression of hepatitis B and that patients with hepatitis B infection should be cautious taking RSV as a dietary supplement.",2016 Apr 21,"['Shi, Yixian', 'Li, Yongjun', 'Huang, Chenjie', 'Ying, Lixiong', 'Xue, Jihua', 'Wu, Haicong', 'Chen, Zhi', 'Yang, Zhenggang']",Sci Rep,,,True
7a7c1c991ee3905b06ca628a523f693a402cc7f1,PMC,Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia,http://dx.doi.org/10.1186/s12879-016-1492-4,PMC4839124,27097824,CC BY,"BACKGROUND: Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) is a poorly understood disease with no known treatments. We describe the clinical features and treatment outcomes of patients with laboratory confirmed MERS-CoV at a regional referral center in the Kingdom of Saudi Arabia. METHODS: In 2014, a retrospective chart review was performed on patients with a laboratory confirmed diagnosis of MERS-CoV to determine clinical and treatment characteristics associated with death. Confounding was evaluated and a multivariate logistic regression was performed to assess the independent effect of treatments administered. RESULTS: Fifty-one patients had an overall mortality of 37 %. Most patients were male (78 %) with a mean age of 54 years. Almost a quarter of the patients were healthcare workers (23.5 %) and 41 % had a known exposure to another person with MERS-CoV. Survival was associated with male gender, working as a healthcare worker, history of hypertension, vomiting on admission, elevated respiratory rate, abnormal lung exam, elevated alanine transaminase (ALT), clearance of MERS-CoV on repeat PCR polymerase chain reaction (PCR) testing, and mycophenolate mofetil treatment. Survival was reduced in the presence of coronary artery disease, hypotension, hypoxemia, CXR (chest X-ray) abnormalities, leukocytosis, creatinine >1 · 5 mg/dL, thrombocytopenia, anemia, and renal failure. In a multivariate analysis of treatments administered, severity of illness was the greatest predictor of reduced survival. CONCLUSIONS: Care for patients with MERS-CoV remains a challenge. In this retrospective cohort, interferon beta and mycophenolate mofetil treatment were predictors of increased survival in the univariate analysis. Severity of illness was the greatest predictor of reduced survival in the multivariate analysis. Larger randomized trials are needed to better evaluate the efficacy of these treatment regimens for MERS-CoV.",2016 Apr 21,"['Al Ghamdi, Mohammed', 'Alghamdi, Khalid M.', 'Ghandoora, Yasmeen', 'Alzahrani, Ameera', 'Salah, Fatmah', 'Alsulami, Abdulmoatani', 'Bawayan, Mayada F.', 'Vaidya, Dhananjay', 'Perl, Trish M.', 'Sood, Geeta']",BMC Infect Dis,,,True
9bacd5e08a587ec2c4a6f367044249fa7c0129bd,PMC,HTS-Driven Discovery of New Chemotypes with West Nile Virus Inhibitory Activity,http://dx.doi.org/10.3390/molecules15031690,PMC4839297,20336008,CC BY,"West Nile virus (WNV) is a positive sense, single-stranded RNA virus that can cause illness in humans when transmitted via mosquito vectors. Unfortunately, no antivirals or vaccines are currently available, and therefore efficient and safe antivirals are urgently needed. We developed a high throughput screen to discover small molecule probes that inhibit virus infection of Vero E6 cells. A primary screen of a 13,001 compound library at a 10 μM final concentration was conducted using the 384-well format. Z′ values ranged from 0.54–0.83 with a median of 0.74. Average S/B was 17 and S/N for each plate ranged from 10.8 to 23.9. Twenty-six compounds showed a dose response in the HT screen and were further evaluated in a time of addition assay and in a titer reduction assay. Seven compounds showed potential as small molecule probes directed at WNV. The hit rate from the primary screen was 0.185% (24 compounds out of 13,001 compounds) and from the secondary screens was 0.053% (7 out of 13,001 compounds) respectively.",2010 Mar 12,"['Chung, Dong Hoon', 'Jonsson, Colleen B.', 'Maddox, Clinton', 'McKellip, Sara N.', 'Moore, Blake. P.', 'Heil, Marintha', 'White, E. Lucile', 'Ananthan, Subramaniam', 'Li, Qianjun', 'Feng, Shuang', 'Rasmussen, Lynn']",Molecules,,,True
0257e6797e12beb91a4a4fcd7130f90d84260718,PMC,Integrated sequence and immunology filovirus database at Los Alamos,http://dx.doi.org/10.1093/database/baw047,PMC4839628,27103629,CC BY,"The Ebola outbreak of 2013–15 infected more than 28 000 people and claimed more lives than all previous filovirus outbreaks combined. Governmental agencies, clinical teams, and the world scientific community pulled together in a multifaceted response ranging from prevention and disease control, to evaluating vaccines and therapeutics in human trials. As this epidemic is finally coming to a close, refocusing on long-term prevention strategies becomes paramount. Given the very real threat of future filovirus outbreaks, and the inherent uncertainty of the next outbreak virus and geographic location, it is prudent to consider the extent and implications of known natural diversity in advancing vaccines and therapeutic approaches. To facilitate such consideration, we have updated and enhanced the content of the filovirus portion of Los Alamos Hemorrhagic Fever Viruses Database. We have integrated and performed baseline analysis of all family Filoviridae sequences deposited into GenBank, with associated immune response data, and metadata, and we have added new computational tools with web-interfaces to assist users with analysis. Here, we (i) describe the main features of updated database, (ii) provide integrated views and some basic analyses summarizing evolutionary patterns as they relate to geo-temporal data captured in the database and (iii) highlight the most conserved regions in the proteome that may be useful for a T cell vaccine strategy. Database URL: www.hfv.lanl.gov",2016 Apr 21,"['Yusim, Karina', 'Yoon, Hyejin', 'Foley, Brian', 'Feng, Shihai', 'Macke, Jennifer', 'Dimitrijevic, Mira', 'Abfalterer, Werner', 'Szinger, James', 'Fischer, Will', 'Kuiken, Carla', 'Korber, Bette']",Database (Oxford),,,True
46ebfbb3db79bab7f78361721e37e8b35a34037e,PMC,Solvent/Detergent Virally Inactivated Serum Eye Drops Restore Healthy Ocular Epithelium in a Rabbit Model of Dry-Eye Syndrome,http://dx.doi.org/10.1371/journal.pone.0153573,PMC4839776,27100624,CC BY,"Application of autologous serum eye drops (SEDs) is a recognized means to treat severe dry-eye syndrome (DES). Due to the inconvenience and difficulty of preparing SEDs from some patients, producing SEDs from allogeneic blood donations is gaining popularity. A major safety concern associated with allogeneic blood is virus transmission. We therefore herein evaluated the possibility of applying a solvent/detergent (S/D) treatment to inactivate viruses and studied the impacts of such treatment of SEDs to resolve DES in a rabbit model. Sera prepared from the blood of five rabbits were pooled and divided into two sub-pools. One was untreated (SEDs), while the other was virally-inactivated with 1% Tri-n-butyl phosphate/1% Triton X-45 at 31°C for 1 h (S/D-SEDs). DES was induced in rabbits using 0.1% benzalkonium chloride (BAC). Rabbits were divided into five groups of two rabbits each. One group was untreated (control), three were treated twice daily for 3 weeks using PBS, SEDs, or S/D-SEDs, and the last received an additional 0.1% BAC (as the negative control). The DES condition was determined by measuring aqueous tear secretion (Schirmer’s test), corneal fluorescein staining, a corneal histologic examination, TUNEL stain apoptosis, and corneal inflammatory marker (tumor necrosis factor-α, interleukin (IL)-1β, IL-8, and IL-6) expressions. We first confirmed that SEDs and S/D-SEDs had similar protein profiles and transforming growth factor (TGF)-β contents. Animal experiments showed that tear secretion did not significantly differ between the SED and S/D-SED groups but was significantly higher than in the PBS group. Eye fluorescein staining revealed dramatic improvements in epithelial defects in groups treated with SEDs or S/D-SEDs, and hematoxylin/eosin staining revealed microscopic epithelial layers similar to those of the untreated controls. Inflammatory markers and TUNEL studies showed that healthy epithelium had been restored in groups treated with SEDs or S/D-SEDs. In conclusion, this preclinical study supports the possibility of using S/D virally inactivated SEDs to treat DES and restore a normal epithelium.",2016 Apr 21,"['Tseng, Ching-Li', 'Chen, Zhi-Yu', 'Renn, Ting-Yi', 'Hsiao, Shun-Hung', 'Burnouf, Thierry']",PLoS One,,,True
2a3a68a67776a01043a6a156b69be803c7118a6d,PMC,The Vpu-interacting Protein SGTA Regulates Expression of a Non-glycosylated Tetherin Species,http://dx.doi.org/10.1038/srep24934,PMC4840321,27103333,CC BY,"The HIV-1 accessory protein Vpu enhances virus release by counteracting the host restriction factor tetherin. To further understand the role of host cell proteins in Vpu function, we carried out yeast two-hybrid screening and identified a previously reported Vpu-interacting host factor, small glutamine-rich tetratricopeptide repeat-containing protein (SGTA). While RNAi-mediated depletion of SGTA did not significantly affect levels of tetherin or virus release efficiency, we observed that overexpression of SGTA inhibited HIV-1 release in a Vpu- and tetherin-independent manner. Overexpression of SGTA in the presence of Vpu, but not in its absence, resulted in a marked stabilization and cytosolic relocalization of a 23-kDa, non-glycosylated tetherin species. Coimmunoprecipitation studies indicated that non-glycosylated tetherin is stabilized through the formation of a ternary SGTA/Vpu/tetherin complex. This accumulation of non-glycosylated tetherin is due to inhibition of its degradation, independent of the ER-associated degradation (ERAD) pathway. Because the SGTA-stabilized tetherin species is partially localized to the cytosol, we propose that overexpression of SGTA in the presence of Vpu blocks the translocation of tetherin across the ER membrane, resulting in cytosolic accumulation of a non-glycosylated tetherin species. Although our results do not provide support for a physiological function of SGTA in HIV-1 replication, they demonstrate that SGTA overexpression regulates tetherin expression and stability, thus providing insights into the function of SGTA in ER translocation and protein degradation.",2016 Apr 22,"['Waheed, Abdul A.', 'MacDonald, Scott', 'Khan, Maisha', 'Mounts, Megan', 'Swiderski, Maya', 'Xu, Yue', 'Ye, Yihong', 'Freed, Eric O.']",Sci Rep,,,True
374da1c5f22a3b6acbea8b991d861026d4620042,PMC,The Vpu-interacting Protein SGTA Regulates Expression of a Non-glycosylated Tetherin Species,http://dx.doi.org/10.1038/srep24934,PMC4840321,27103333,CC BY,"The HIV-1 accessory protein Vpu enhances virus release by counteracting the host restriction factor tetherin. To further understand the role of host cell proteins in Vpu function, we carried out yeast two-hybrid screening and identified a previously reported Vpu-interacting host factor, small glutamine-rich tetratricopeptide repeat-containing protein (SGTA). While RNAi-mediated depletion of SGTA did not significantly affect levels of tetherin or virus release efficiency, we observed that overexpression of SGTA inhibited HIV-1 release in a Vpu- and tetherin-independent manner. Overexpression of SGTA in the presence of Vpu, but not in its absence, resulted in a marked stabilization and cytosolic relocalization of a 23-kDa, non-glycosylated tetherin species. Coimmunoprecipitation studies indicated that non-glycosylated tetherin is stabilized through the formation of a ternary SGTA/Vpu/tetherin complex. This accumulation of non-glycosylated tetherin is due to inhibition of its degradation, independent of the ER-associated degradation (ERAD) pathway. Because the SGTA-stabilized tetherin species is partially localized to the cytosol, we propose that overexpression of SGTA in the presence of Vpu blocks the translocation of tetherin across the ER membrane, resulting in cytosolic accumulation of a non-glycosylated tetherin species. Although our results do not provide support for a physiological function of SGTA in HIV-1 replication, they demonstrate that SGTA overexpression regulates tetherin expression and stability, thus providing insights into the function of SGTA in ER translocation and protein degradation.",2016 Apr 22,"['Waheed, Abdul A.', 'MacDonald, Scott', 'Khan, Maisha', 'Mounts, Megan', 'Swiderski, Maya', 'Xu, Yue', 'Ye, Yihong', 'Freed, Eric O.']",Sci Rep,,,False
9c5447c495379f968aacd114e73a03039ccfd69d,PMC,Epidemic strain YC2014 of porcine epidemic diarrhea virus could provide piglets against homologous challenge,http://dx.doi.org/10.1186/s12985-016-0529-z,PMC4840883,27103490,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is the main causative agent of porcine epidemic diarrhea (PED). Since December 2010, a large-scale outbreak of diarrhea has been observed in swine farms in China. Accumulated evidence indicates that this large-scale outbreak of diarrhea were caused by highly virulent PEDV variants. METHODS: A PEDV strain, YC2014, was isolated from intestinal samples of suckling piglets with acute diarrhea in 2014. The complete genomic sequence of YC2014 and the nucleotide sequence of S gene were aligned with sequences of published isolates using MEGA 5.1 software. The immune protective efficiency of YC2014 were determined by testing PEDV neutralizing antibodies in sera, the colostrum and the milk on 7th day after farrowing of the immunized sows. The diarrhea symptoms of piglets after challenge were also observed. RESULTS: Phylogenetic analysis of the complete genomic sequence of YC2014 and the nucleotide sequence of S gene demonstrated that the YC2014 PEDV strain was clustered with the PEDV epidemic strains, with >99 % nucleotide identity to these PEDV strains. The S gene sequence of YC2014 shared only 93.9 % ~ 94.4 % identities with classical CV777, DR13 and JS2008 strains, with 15 nucleotide insertion in three sites and three nucleotide deletion in one site. The amino acid (AA) sequence of S gene of YC2014 shared only 92.8 % ~ 93.4 % identities with classical CV777, DR13 and JS2008 strains, with 5 AA insertion in two sites and 1 AA deletion in one site. In the immune protective efficiency tests, the neutralizing antibody titers in sera, the colostrum and the milk on 7th day after farrowing of the inactivated YC2014 PEDV strain immunized group were significantly higher than the inactivated CV777 immunized group and the inactivated DR13 immunized group (P < 0.05). The traditional inactivated PEDV vaccines made from CV777 or DR13 could not protect piglets from YC2014 challenge, while inactivated YC2014 could provide piglets with 100 % protection against YC2014 challenge. CONCLUSIONS: The results showed that, great antigenicity variation had occurred to this YC2014 PEDV strain. The YC2014 PEDV strain could provide piglets against homologous challenge. It is critical for future pathogenic and antigenic studies, as well as for the development of effective preventive and control vaccines against PEDV.",2016 Apr 22,"['Lin, Huixing', 'Chen, Lei', 'Gao, Lu', 'Yuan, Xiaomin', 'Ma, Zhe', 'Fan, Hongjie']",Virol J,,,True
f42073cb33dc2aa926898dd2ab05da828f8e7790,PMC,Open drug discovery for the Zika virus,http://dx.doi.org/10.12688/f1000research.8013.1,PMC4841202,27134728,CC BY,"The Zika virus (ZIKV) outbreak in the Americas has caused global concern that we may be on the brink of a healthcare crisis. The lack of research on ZIKV in the over 60 years that we have known about it has left us with little in the way of starting points for drug discovery. Our response can build on previous efforts with virus outbreaks and lean heavily on work done on other flaviviruses such as dengue virus. We provide some suggestions of what might be possible and propose an open drug discovery effort that mobilizes global science efforts and provides leadership, which thus far has been lacking. We also provide a listing of potential resources and molecules that could be prioritized for testing as in vitro assays for ZIKV are developed. We propose also that in order to incentivize drug discovery, a neglected disease priority review voucher should be available to those who successfully develop an FDA approved treatment. Learning from the response to the ZIKV, the approaches to drug discovery used and the success and failures will be critical for future infectious disease outbreaks.",2016 Feb 9,"['Ekins, Sean', 'Mietchen, Daniel', 'Coffee, Megan', 'Stratton, Thomas P', 'Freundlich, Joel S', 'Freitas-Junior, Lucio', 'Muratov, Eugene', 'Siqueira-Neto, Jair', 'Williams, Antony J', 'Andrade, Carolina']",F1000Res,,,True
60b69719c85b64d84bb0b4621ed53108914aebe8,PMC,"Pathogenicity of Genetically Similar, H5N1 Highly Pathogenic Avian Influenza Virus Strains in Chicken and the Differences in Sensitivity among Different Chicken Breeds",http://dx.doi.org/10.1371/journal.pone.0153649,PMC4841636,27078641,CC BY,"Differences in the pathogenicity of genetically closely related H5N1 highly pathogenic avian influenza viruses (HPAIVs) were evaluated in White Leghorn chickens. These viruses varied in the clinical symptoms they induced, including lethality, virus shedding, and replication in host tissues. A comparison of the host responses in the lung, brain, and spleen suggested that the differences in viral replication efficiency were related to the host cytokine response at the early phase of infection, especially variations in the proinflammatory cytokine IL-6. Based on these findings, we inoculated the virus that showed the mildest pathogenicity among the five tested, A/pigeon/Thailand/VSMU-7-NPT/2004, into four breeds of Thai indigenous chicken, Phadu-Hung-Dang (PHD), Chee, Dang, and Luang-Hung-Khao (LHK), to explore effects of genetic background on host response. Among these breeds, Chee, Dang, and LHK showed significantly longer survival times than White Leghorns. Virus shedding from dead Thai indigenous chickens was significantly lower than that from White Leghorns. Although polymorphisms were observed in the Mx and MHC class I genes, there was no significant association between the polymorphisms in these loci and resistance to HPAIV.",2016 Apr 14,"['Matsuu, Aya', 'Kobayashi, Tomoko', 'Patchimasiri, Tuangthong', 'Shiina, Takashi', 'Suzuki, Shingo', 'Chaichoune, Kridsada', 'Ratanakorn, Parntep', 'Hiromoto, Yasuaki', 'Abe, Haruka', 'Parchariyanon, Sujira', 'Saito, Takehiko']",PLoS One,,,True
ad3b8061a983745471ac96a30d534b00f57a9ffb,PMC,Comparative analysis of viral RNA signatures on different RIG-I-like receptors,http://dx.doi.org/10.7554/eLife.11275,PMC4841775,27011352,CC BY,"The RIG-I-like receptors (RLRs) play a major role in sensing RNA virus infection to initiate and modulate antiviral immunity. They interact with particular viral RNAs, most of them being still unknown. To decipher the viral RNA signature on RLRs during viral infection, we tagged RLRs (RIG-I, MDA5, LGP2) and applied tagged protein affinity purification followed by next-generation sequencing (NGS) of associated RNA molecules. Two viruses with negative- and positive-sense RNA genome were used: measles (MV) and chikungunya (CHIKV). NGS analysis revealed that distinct regions of MV genome were specifically recognized by distinct RLRs: RIG-I recognized defective interfering genomes, whereas MDA5 and LGP2 specifically bound MV nucleoprotein-coding region. During CHIKV infection, RIG-I associated specifically to the 3’ untranslated region of viral genome. This study provides the first comparative view of the viral RNA ligands for RIG-I, MDA5 and LGP2 in the presence of infection. DOI: http://dx.doi.org/10.7554/eLife.11275.001",,"['Sanchez David, Raul Y', 'Combredet, Chantal', 'Sismeiro, Odile', 'Dillies, Marie-Agnès', 'Jagla, Bernd', 'Coppée, Jean-Yves', 'Mura, Marie', 'Guerbois Galla, Mathilde', 'Despres, Philippe', 'Tangy, Frédéric', 'Komarova, Anastassia V']",eLife.; 5:e11275,,,True
3619c9e99ff6ceb2fa038d13239e6fce4e818995,PMC,Comparison of SYBR green I real-time RT-PCR with conventional agarose gel-based RT-PCR for the diagnosis of infectious bronchitis virus infection in chickens in Morocco,http://dx.doi.org/10.1186/s13104-016-2037-z,PMC4841946,27106608,CC BY,"BACKGROUND: A rapid, sensitive, and specific molecular method for the diagnosis of infectious bronchitis virus (IBV) infection is important in curbing infectious bronchitis outbreaks in Morocco and other countries. METHODS: In this study, an easy-to-perform SYBR green I real-time reverse transcriptase polymerase chain reaction (RT-PCR) targeting the nucleocapsid gene of IBV was developed and compared with conventional agarose gel-based RT-PCR for the detection of IBV infection. RESULTS: We found that the SYBR green I real-time RT-PCR was at least 10 times more sensitive than the agarose gel electrophoresis detection method. The assay exhibited high specificity for IBV infection. All negative controls, such as Newcastle disease virus, infectious bursal disease virus, and avian influenza virus, were not detected. CONCLUSION: The SYBR green I real-time RT-PCR test described herein can be used to rapidly distinguish IBV from other respiratory pathogens, which is important for diagnosis and control of infectious bronchitis outbreaks in Morocco. The test is a valuable and useful method as a routine assay for diagnosis of clinical IBV infection in commercial chickens.",2016 Apr 22,"['Fellahi, Siham', 'Harrak, Mehdi El', 'Kuhn, Jens H.', 'Sebbar, Ghizlane', 'Bouaiti, El Arbi', 'Khataby, Khadija', 'Fihri, Ouafae Fassi', 'Houadfi, Mohammed El', 'Ennaji, My Mustapha']",BMC Res Notes,,,True
27dfdf0c086653e07dbc5d50ed1d2bc9228cfca8,PMC,Correction: Middle East Respiratory Syndrome Coronavirus Intra-Host Populations Are Characterized by Numerous High Frequency Variants,http://dx.doi.org/10.1371/journal.pone.0154424,PMC4844146,27111439,CC BY,,2016 Apr 25,"['Borucki, Monica K.', 'Lao, Victoria', 'Hwang, Mona', 'Gardner, Shea', 'Adney, Danielle', 'Munster, Vincent', 'Bowen, Richard', 'Allen, Jonathan E.']",PLoS One,,,False
e1f84229bcacd4ea32af6127963a174f888acb09,PMC,Identification of critical residues in Hepatitis E virus macro domain involved in its interaction with viral methyltransferase and ORF3 proteins,http://dx.doi.org/10.1038/srep25133,PMC4844956,27113483,CC BY,"Hepatitis E virus (HEV) is a major cause of hepatitis in normal and organ transplant individuals. HEV open reading frame-1 encodes a polypeptide comprising of the viral nonstructural proteins as well as domains of unknown function such as the macro domain (X-domain), V, DUF3729 and Y. The macro domain proteins are ubiquitously present from prokaryotes to human and in many positive-strand RNA viruses, playing important roles in multiple cellular processes. Towards understanding the function of the HEV macro domain, we characterized its interaction partners among other HEV encoded proteins. Here, we report that the HEV X-domain directly interacts with the viral methyltransferase and the ORF3 proteins. ORF3 association with the X-domain was mediated through two independent motifs, located within its N-terminal 35aa (amino acids) and C-terminal 63-123aa. Methyltransferase interaction domain was mapped to N-terminal 30-90aa. The X-domain interacted with both ORF3 and methyltransferase through its C-terminal region, involving 66(th),67(th) isoleucine and 101(st),102(nd) leucine, conserved across HEV genotypes. Furthermore, ORF3 and methyltransferase competed with each other for associating with the X-domain. These findings provide molecular understanding of the interaction between the HEV macro domain, methyltransferase and ORF3, suggesting an important role of the macro domain in the life cycle of HEV.",2016 Apr 26,"['Anang, Saumya', 'Subramani, Chandru', 'Nair, Vidya P.', 'Kaul, Sheetal', 'Kaushik, Nidhi', 'Sharma, Chandresh', 'Tiwari, Ashutosh', 'Ranjith-Kumar, CT', 'Surjit, Milan']",Sci Rep,,,True
2ccbb7b5eeb50c2d41a71500cd920a614a402a0e,PMC,Identification of critical residues in Hepatitis E virus macro domain involved in its interaction with viral methyltransferase and ORF3 proteins,http://dx.doi.org/10.1038/srep25133,PMC4844956,27113483,CC BY,"Hepatitis E virus (HEV) is a major cause of hepatitis in normal and organ transplant individuals. HEV open reading frame-1 encodes a polypeptide comprising of the viral nonstructural proteins as well as domains of unknown function such as the macro domain (X-domain), V, DUF3729 and Y. The macro domain proteins are ubiquitously present from prokaryotes to human and in many positive-strand RNA viruses, playing important roles in multiple cellular processes. Towards understanding the function of the HEV macro domain, we characterized its interaction partners among other HEV encoded proteins. Here, we report that the HEV X-domain directly interacts with the viral methyltransferase and the ORF3 proteins. ORF3 association with the X-domain was mediated through two independent motifs, located within its N-terminal 35aa (amino acids) and C-terminal 63-123aa. Methyltransferase interaction domain was mapped to N-terminal 30-90aa. The X-domain interacted with both ORF3 and methyltransferase through its C-terminal region, involving 66(th),67(th) isoleucine and 101(st),102(nd) leucine, conserved across HEV genotypes. Furthermore, ORF3 and methyltransferase competed with each other for associating with the X-domain. These findings provide molecular understanding of the interaction between the HEV macro domain, methyltransferase and ORF3, suggesting an important role of the macro domain in the life cycle of HEV.",2016 Apr 26,"['Anang, Saumya', 'Subramani, Chandru', 'Nair, Vidya P.', 'Kaul, Sheetal', 'Kaushik, Nidhi', 'Sharma, Chandresh', 'Tiwari, Ashutosh', 'Ranjith-Kumar, CT', 'Surjit, Milan']",Sci Rep,,,False
7e4299dd78b35e5223c34355cd13c9c99ed72c25,PMC,Divergent bufavirus harboured in megabats represents a new lineage of parvoviruses,http://dx.doi.org/10.1038/srep24257,PMC4845017,27113297,CC BY,"Bufavirus is a recently recognized member of the genus Protoparvovirus in the subfamily Parvovirinae. It has been reported that human bufavirus was detected predominantly in patients with diarrhoea in several countries. However, little is known about bufavirus or its close relatives in nonhuman mammals. In this study, we performed nested-PCR screening and identified bufavirus from 12 megabats of Pteropus spp. in Indonesia. Furthermore, we determined nearly the full genome sequence of a novel megabat-borne bufavirus, tentatively named megabat bufavirus 1. Phylogenetic analyses showed that megabat bufavirus 1 clustered with known protoparvoviruses, including human bufavirus but represented a distinct lineage of bufavirus. Our analyses also inferred phylogenetic relationships among animal-borne bufaviruses recently reported by other studies. Recombination analyses suggested that the most common recent ancestor of megabat bufavirus 1 might have arisen from multiple genetic recombination events. These results characterized megabat bufavirus 1 as the first protoparvovirus discovered from megabats and indicates the high genetic divergence of bufavirus.",2016 Apr 26,"['Sasaki, Michihito', 'Gonzalez, Gabriel', 'Wada, Yuji', 'Setiyono, Agus', 'Handharyani, Ekowati', 'Rahmadani, Ibenu', 'Taha, Siswatiana', 'Adiani, Sri', 'Latief, Munira', 'Kholilullah, Zainal Abidin', 'Subangkit, Mawar', 'Kobayashi, Shintaro', 'Nakamura, Ichiro', 'Kimura, Takashi', 'Orba, Yasuko', 'Ito, Kimihito', 'Sawa, Hirofumi']",Sci Rep,,,True
80850d03f16060e460bd50e5622e2196c0622f54,PMC,A web-based resource for designing therapeutics against Ebola Virus,http://dx.doi.org/10.1038/srep24782,PMC4845023,27113850,CC BY,"In this study, we describe a web-based resource, developed for assisting the scientific community in designing an effective therapeutics against the Ebola virus. Firstly, we predicted and identified experimentally validated epitopes in each of the antigens/proteins of the five known ebolaviruses. Secondly, we generated all the possible overlapping 9mer peptides from the proteins of ebolaviruses. Thirdly, conserved peptides across all the five ebolaviruses (four human pathogenic species) with no identical sequence in the human proteome, based on 1000 Genomes project, were identified. Finally, we identified peptide or epitope-based vaccine candidates that could activate both the B- and T-cell arms of the immune system. In addition, we also identified efficacious siRNAs against the mRNA transcriptome (absent in human transcriptome) of all the five ebolaviruses. It was observed that three species can potentially be targeted by a single siRNA (19mer) and 75 siRNAs can potentially target at least two species. A web server, EbolaVCR, has been developed that incorporates all the above information and useful computational tools (http://crdd.osdd.net/oscadd/ebola/).",2016 Apr 26,"['Dhanda, Sandeep Kumar', 'Chaudhary, Kumardeep', 'Gupta, Sudheer', 'Brahmachari, Samir Kumar', 'Raghava, Gajendra P. S.']",Sci Rep,,,True
8e47f269f449983eb0dc70d257f09f27b1e81247,PMC,Antiviral Role of IFITM Proteins in African Swine Fever Virus Infection,http://dx.doi.org/10.1371/journal.pone.0154366,PMC4846163,27116236,CC BY,"The interferon-induced transmembrane (IFITM) protein family is a group of antiviral restriction factors that impair flexibility and inhibit membrane fusion at the plasma or the endosomal membrane, restricting viral progression at entry. While IFITMs are widely known to inhibit several single-stranded RNA viruses, there are limited reports available regarding their effect in double-stranded DNA viruses. In this work, we have analyzed a possible antiviral function of IFITMs against a double stranded DNA virus, the African swine fever virus (ASFV). Infection with cell-adapted ASFV isolate Ba71V is IFN sensitive and it induces IFITMs expression. Interestingly, high levels of IFITMs caused a collapse of the endosomal pathway to the perinuclear area. Given that ASFV entry is strongly dependent on endocytosis, we investigated whether IFITM expression could impair viral infection. Expression of IFITM1, 2 and 3 reduced virus infectivity in Vero cells, with IFITM2 and IFITM3 having an impact on viral entry/uncoating. The role of IFITM2 in the inhibition of ASFV in Vero cells could be related to impaired endocytosis-mediated viral entry and alterations in the cholesterol efflux, suggesting that IFITM2 is acting at the late endosome, preventing the decapsidation stage of ASFV.",2016 Apr 26,"['Muñoz-Moreno, Raquel', 'Cuesta-Geijo, Miguel Ángel', 'Martínez-Romero, Carles', 'Barrado-Gil, Lucía', 'Galindo, Inmaculada', 'García-Sastre, Adolfo', 'Alonso, Covadonga']",PLoS One,,,True
e2904c6e462291682dc4d65ce47a91bdc8509747,PMC,Identification of miRNomes reveals ssc-miR-30d-R_1 as a potential therapeutic target for PRRS viral infection,http://dx.doi.org/10.1038/srep24854,PMC4846818,27117627,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) is known to cause reproductive disorders, such as abortion, in pregnant sows as well as immunosuppressive respiratory complications, leading to severe respiratory tract infections in young pigs. In this study, an in-depth analysis of the miRNomes in mock- and virus-infected pig lungs was carried out. We found that highly expressed ssc-miR-30d-R_1 was decreased in infected lungs, and reduced levels were significantly correlated with infection by PRRSV. Moreover, ssc-miR-30d-R_1 was shown to target Toll-like receptor 4 (TLR4) and to suppress the production of immune cytokines through inhibition of the TLR4/MyD88/NF-κB pathway. ssc-miR-30d-R_1 significantly reduced viral infections and pathological changes in pig lungs in vivo. Our current study reveals the miRNomes of PRRSV-infected pig lungs and indicates that ssc-miR-30d-R_1 is potential therapeutic agent for controlling PRRSV infection.",2016 Apr 27,"['Wang, Chengmin', 'Zhang, Yanyu', 'Luo, Jing', 'Ding, Hua', 'Liu, Shelan', 'Amer, Said', 'Xie, Li', 'Lyv, Wenting', 'Su, Wen', 'Li, Meng', 'Sun, Qinmiao', 'Dai, Jiayin', 'He, Hongxuan']",Sci Rep,,,True
b98e584fe5f4e0d10462c8475bd596fc004de57c,PMC,Identification of miRNomes reveals ssc-miR-30d-R_1 as a potential therapeutic target for PRRS viral infection,http://dx.doi.org/10.1038/srep24854,PMC4846818,27117627,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) is known to cause reproductive disorders, such as abortion, in pregnant sows as well as immunosuppressive respiratory complications, leading to severe respiratory tract infections in young pigs. In this study, an in-depth analysis of the miRNomes in mock- and virus-infected pig lungs was carried out. We found that highly expressed ssc-miR-30d-R_1 was decreased in infected lungs, and reduced levels were significantly correlated with infection by PRRSV. Moreover, ssc-miR-30d-R_1 was shown to target Toll-like receptor 4 (TLR4) and to suppress the production of immune cytokines through inhibition of the TLR4/MyD88/NF-κB pathway. ssc-miR-30d-R_1 significantly reduced viral infections and pathological changes in pig lungs in vivo. Our current study reveals the miRNomes of PRRSV-infected pig lungs and indicates that ssc-miR-30d-R_1 is potential therapeutic agent for controlling PRRSV infection.",2016 Apr 27,"['Wang, Chengmin', 'Zhang, Yanyu', 'Luo, Jing', 'Ding, Hua', 'Liu, Shelan', 'Amer, Said', 'Xie, Li', 'Lyv, Wenting', 'Su, Wen', 'Li, Meng', 'Sun, Qinmiao', 'Dai, Jiayin', 'He, Hongxuan']",Sci Rep,,,False
465ce310d1edd953819b77c96fa57e62d8cbc042,PMC,Antiviral Activity of Graphene–Silver Nanocomposites against Non-Enveloped and Enveloped Viruses,http://dx.doi.org/10.3390/ijerph13040430,PMC4847092,27104546,CC BY,"The discovery of novel antiviral materials is important because many infectious diseases are caused by viruses. Silver nanoparticles have demonstrated strong antiviral activity, and graphene is a potential antimicrobial material due to its large surface area, high carrier mobility, and biocompatibility. No studies on the antiviral activity of nanomaterials on non-enveloped viruses have been reported. To investigate the antiviral activity of graphene oxide (GO) sheets and GO sheets with silver particles (GO-Ag) against enveloped and non-enveloped viruses, feline coronavirus (FCoV) with an envelope and infectious bursal disease virus (IBDV) without an envelope were chosen. The morphology and sizes of GO and GO-Ag were characterized by transmission, scanning electron microscopy, and X-ray diffraction. A virus inhibition assay was used to identify the antiviral activity of GO and GO-Ag. Go-Ag inhibited 25% of infection by FCoV and 23% by IBDV, whereas GO only inhibited 16% of infection by FCoV but showed no antiviral activity against the infection by IBDV. Further application of GO and GO-Ag can be considered for personal protection equipment to decrease the transmission of viruses.",2016 Apr 19,"['Chen, Yi-Ning', 'Hsueh, Yi-Huang', 'Hsieh, Chien-Te', 'Tzou, Dong-Ying', 'Chang, Pai-Ling']",Int J Environ Res Public Health,,,True
f54e577394738498bde347596b1dd5b1156d235d,PMC,Comparison of molecular detection methods for pertussis in children during a state-wide outbreak,http://dx.doi.org/10.1186/s12941-016-0142-4,PMC4847268,27121506,CC BY,"A state-wide pertussis outbreak occurred in Washington during the winter–spring months of 2012, concurrent with respiratory viral season. We compared performance characteristics of a laboratory-developed pertussis PCR (LD-PCR for Bordetella pertussis, Bordetella parapertussis, and Bordetella holmesii) and rapid multiplex PCR (RM-PCR) for respiratory viruses (FilmArray™, BioFire, B. pertussis data unblinded following FDA approval post outbreak). We analyzed three cohorts of patients using physician testing orders as a proxy for clinical suspicion for pertussis or respiratory viruses: Cohort 1, tested by LD-PCR for pertussis pathogens only by nasopharyngeal swab; Cohort 2, by RM-PCR for respiratory viruses only by mid-nasal turbinate swab; and Cohort 3, by both methods. B. pertussis was detected in a total of 25 of the 490 patients in Cohort 3 in which LD-PCR detected 20/25 (80 %) cases and the RM-PCR detected 24/25 (96 %; p = 0.2). Pertussis pathogens were detected in 21/584 (3.6 %) of samples from Cohort 1 where clinicians had a relatively strong suspicion for pertussis. In contrast, B. pertussis was detected in only 4/3071 (0.1 %) specimens from Cohort 2 where suspicion for pertussis was lower (p < 0.001 for comparison with Cohort 1). In summary, the two laboratory methods were comparable for the detection of B. pertussis.",2016 Apr 27,"['Qin, X.', 'Zerr, D. M.', 'Kronman, M. P.', 'Adler, A. L.', 'Berry, J. E.', 'Rich, S.', 'Buccat, A. M.', 'Xu, M.', 'Englund, J. A.']",Ann Clin Microbiol Antimicrob,,,True
0180abece22ace6548f4601591c98059808d0509,PMC,Enterovirus D68 Infections Associated with Severe Respiratory Illness in Elderly Patients and Emergence of a Novel Clade in Hong Kong,http://dx.doi.org/10.1038/srep25147,PMC4848506,27121085,CC BY,"Despite the recent emergence of enterovirus D68 (EV-D68), its clinical impact on adult population is less well defined. To better define the epidemiology of EV-D68, 6,800 nasopharyngeal aspirates (NPAs) from 2010–2014 were subject to EV-D68 detection by RT-PCR and sequencing of 5′UTR and partial VP1. EV-D68 was detected in 30 (0.44%) NPAs from 22 children and 8 adults/elderlies. Sixteen patients (including five elderly) (53%) had pneumonia and 13 (43%) patients were complicated by small airway disease exacerbation. Phylogenetic analysis of VP1, 2C and 3D regions showed four distinct lineages of EV-D68, clade A1, A2, B1 and B3, with adults/elderlies exclusively infected by clade A2. The potentially new clade, B3, has emerged in 2014, while strains closely related to recently emerged B1 strains in the United States were also detected as early as 2011 in Hong Kong. The four lineages possessed distinct aa sequence patterns in BC and DE loops. Amino acid residues 97 and 140, within BC and DE-surface loops of VP1 respectively, were under potential positive selection. EV-D68 infections in Hong Kong usually peak in spring/summer, though with a delayed autumn/winter peak in 2011. This report suggests that EV-D68 may cause severe respiratory illness in adults/elderlies with underlying co-morbidities.",2016 Apr 28,"['Lau, Susanna K. P.', 'Yip, Cyril C. Y.', 'Zhao, Pyrear Su-Hui', 'Chow, Wang-Ngai', 'To, Kelvin K. W.', 'Wu, Alan K. L.', 'Yuen, Kwok-Yung', 'Woo, Patrick C. Y.']",Sci Rep,,,True
c5c285ad0c47bd3d84e5086846f474479a545da2,PMC,Enterovirus D68 Infections Associated with Severe Respiratory Illness in Elderly Patients and Emergence of a Novel Clade in Hong Kong,http://dx.doi.org/10.1038/srep25147,PMC4848506,27121085,CC BY,"Despite the recent emergence of enterovirus D68 (EV-D68), its clinical impact on adult population is less well defined. To better define the epidemiology of EV-D68, 6,800 nasopharyngeal aspirates (NPAs) from 2010–2014 were subject to EV-D68 detection by RT-PCR and sequencing of 5′UTR and partial VP1. EV-D68 was detected in 30 (0.44%) NPAs from 22 children and 8 adults/elderlies. Sixteen patients (including five elderly) (53%) had pneumonia and 13 (43%) patients were complicated by small airway disease exacerbation. Phylogenetic analysis of VP1, 2C and 3D regions showed four distinct lineages of EV-D68, clade A1, A2, B1 and B3, with adults/elderlies exclusively infected by clade A2. The potentially new clade, B3, has emerged in 2014, while strains closely related to recently emerged B1 strains in the United States were also detected as early as 2011 in Hong Kong. The four lineages possessed distinct aa sequence patterns in BC and DE loops. Amino acid residues 97 and 140, within BC and DE-surface loops of VP1 respectively, were under potential positive selection. EV-D68 infections in Hong Kong usually peak in spring/summer, though with a delayed autumn/winter peak in 2011. This report suggests that EV-D68 may cause severe respiratory illness in adults/elderlies with underlying co-morbidities.",2016 Apr 28,"['Lau, Susanna K. P.', 'Yip, Cyril C. Y.', 'Zhao, Pyrear Su-Hui', 'Chow, Wang-Ngai', 'To, Kelvin K. W.', 'Wu, Alan K. L.', 'Yuen, Kwok-Yung', 'Woo, Patrick C. Y.']",Sci Rep,,,False
6695dd7f637481312d8589cbc32aa3bef1c816a4,PMC,Enterovirus Control of Translation and RNA Granule Stress Responses,http://dx.doi.org/10.3390/v8040093,PMC4848588,27043612,CC BY,"Enteroviruses such as poliovirus (PV) and coxsackievirus B3 (CVB3) have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome. Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs) and processing bodies (P-bodies, PBs), which are stress-responsive dynamic structures involved in repression of gene expression. This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections. In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation.",2016 Mar 30,"Lloyd, Richard E.",Viruses,,,True
1d14e19f66d1a9c36b98aa2365aab80e9845616e,PMC,Current Approaches for Diagnosis of Influenza Virus Infections in Humans,http://dx.doi.org/10.3390/v8040096,PMC4848591,27077877,CC BY,"Despite significant advancement in vaccine and virus research, influenza continues to be a major public health concern. Each year in the United States of America, influenza viruses are responsible for seasonal epidemics resulting in over 200,000 hospitalizations and 30,000–50,000 deaths. Accurate and early diagnosis of influenza viral infections are critical for rapid initiation of antiviral therapy to reduce influenza related morbidity and mortality both during seasonal epidemics and pandemics. Several different approaches are currently available for diagnosis of influenza infections in humans. These include viral isolation in cell culture, immunofluorescence assays, nucleic acid amplification tests, immunochromatography-based rapid diagnostic tests, etc. Newer diagnostic approaches are being developed to overcome the limitations associated with some of the conventional detection methods. This review discusses diagnostic approaches currently available for detection of influenza viruses in humans.",2016 Apr 12,"['Vemula, Sai Vikram', 'Zhao, Jiangqin', 'Liu, Jikun', 'Wang, Xue', 'Biswas, Santanu', 'Hewlett, Indira']",Viruses,,,True
43740caefa35d11ce1aa130cd8ca86b60442b046,PMC,Shutoff of Host Gene Expression in Influenza A Virus and Herpesviruses: Similar Mechanisms and Common Themes,http://dx.doi.org/10.3390/v8040102,PMC4848596,27092522,CC BY,"The ability to shut off host gene expression is a shared feature of many viral infections, and it is thought to promote viral replication by freeing host cell machinery and blocking immune responses. Despite the molecular differences between viruses, an emerging theme in the study of host shutoff is that divergent viruses use similar mechanisms to enact host shutoff. Moreover, even viruses that encode few proteins often have multiple mechanisms to affect host gene expression, and we are only starting to understand how these mechanisms are integrated. In this review we discuss the multiplicity of host shutoff mechanisms used by the orthomyxovirus influenza A virus and members of the alpha- and gamma-herpesvirus subfamilies. We highlight the surprising similarities in their mechanisms of host shutoff and discuss how the different mechanisms they use may play a coordinated role in gene regulation.",2016 Apr 16,"['Rivas, Hembly G.', 'Schmaling, Summer K.', 'Gaglia, Marta M.']",Viruses,,,True
dc69e220d40597887fac3851a1601408fe7bf568,PMC,Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus,http://dx.doi.org/10.3390/v8040106,PMC4848600,27110812,CC BY,"Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.",2016 Apr 21,"['Zivcec, Marko', 'Scholte, Florine E. M.', 'Spiropoulou, Christina F.', 'Spengler, Jessica R.', 'Bergeron, Éric']",Viruses,,,True
ed47ed886ac68059ec1d579c70759578c3d766e5,PMC,Non-hydrolyzable Diubiquitin Probes Reveal Linkage-Specific Reactivity of Deubiquitylating Enzymes Mediated by S2 Pockets,http://dx.doi.org/10.1016/j.chembiol.2016.03.009,PMC4850247,27066941,CC BY,"Ubiquitin chains are important post-translational modifications that control a large number of cellular processes. Chains can be formed via different linkages, which determines the type of signal they convey. Deubiquitylating enzymes (DUBs) regulate ubiquitylation status by trimming or removing chains from attached proteins. DUBs can contain several ubiquitin-binding pockets, which confer specificity toward differently linked chains. Most tools for monitoring DUB specificity target binding pockets on opposing sides of the active site; however, some DUBs contain additional pockets. Therefore, reagents targeting additional pockets are essential to fully understand linkage specificity. We report the development of active site-directed probes and fluorogenic substrates, based on non-hydrolyzable diubiquitin, that are equipped with a C-terminal warhead or a fluorogenic activity reporter moiety. We demonstrate that various DUBs in lysates display differential reactivity toward differently linked diubiquitin probes, as exemplified by the proteasome-associated DUB USP14. In addition, OTUD2 and OTUD3 show remarkable linkage-specific reactivity with our diubiquitin-based reagents.",2016 Apr 21,"['Flierman, Dennis', 'van\xa0der\xa0Heden\xa0van\xa0Noort, Gerbrand\xa0J.', 'Ekkebus, Reggy', 'Geurink, Paul\xa0P.', 'Mevissen, Tycho\xa0E.T.', 'Hospenthal, Manuela\xa0K.', 'Komander, David', 'Ovaa, Huib']",Cell Chem Biol,,,False
e733dff32efffe3238869aa7aeea1904fe814f5b,PMC,Non-hydrolyzable Diubiquitin Probes Reveal Linkage-Specific Reactivity of Deubiquitylating Enzymes Mediated by S2 Pockets,http://dx.doi.org/10.1016/j.chembiol.2016.03.009,PMC4850247,27066941,CC BY,"Ubiquitin chains are important post-translational modifications that control a large number of cellular processes. Chains can be formed via different linkages, which determines the type of signal they convey. Deubiquitylating enzymes (DUBs) regulate ubiquitylation status by trimming or removing chains from attached proteins. DUBs can contain several ubiquitin-binding pockets, which confer specificity toward differently linked chains. Most tools for monitoring DUB specificity target binding pockets on opposing sides of the active site; however, some DUBs contain additional pockets. Therefore, reagents targeting additional pockets are essential to fully understand linkage specificity. We report the development of active site-directed probes and fluorogenic substrates, based on non-hydrolyzable diubiquitin, that are equipped with a C-terminal warhead or a fluorogenic activity reporter moiety. We demonstrate that various DUBs in lysates display differential reactivity toward differently linked diubiquitin probes, as exemplified by the proteasome-associated DUB USP14. In addition, OTUD2 and OTUD3 show remarkable linkage-specific reactivity with our diubiquitin-based reagents.",2016 Apr 21,"['Flierman, Dennis', 'van\xa0der\xa0Heden\xa0van\xa0Noort, Gerbrand\xa0J.', 'Ekkebus, Reggy', 'Geurink, Paul\xa0P.', 'Mevissen, Tycho\xa0E.T.', 'Hospenthal, Manuela\xa0K.', 'Komander, David', 'Ovaa, Huib']",Cell Chem Biol,,,False
d3ca5f2f620d495c747bac2a00b3446b392f7535,PMC,Direct molecular detection of a broad range of bacterial and viral organisms and Streptococcus pneumoniae vaccine serotypes in children with otitis media with effusion,http://dx.doi.org/10.1186/s13104-016-2040-4,PMC4850712,27130295,CC BY,"BACKGROUND: Otitis media with effusion (OME) causes significant morbidity in children, but the causes of OME and methods for prevention are unclear. To look for potential infectious etiologies, we performed a pilot study using multiple-target real-time polymerase chain reaction (qPCR) for 27 infectious agents, including nine bacterial organisms and 18 respiratory viruses in middle ear fluids (MEFs) from children with OME. QPCR was also performed for the 13 Streptococcus pneumoniae serotypes contained in the current vaccine. RESULTS: Forty-eight MEF samples were obtained and qPCR detected bacterial nucleic acid (NA) in 39/48 (81 %) and viral NA in 7/48 (15 %). Alloiococcus otitidis and S. pneumoniae were both detected in 15/48 (31 %) MEFs, followed by M. catarrhalis in 14/48 (29 %), H. influenzae in 5/48 (10 %) and M. pneumoniae in 4/48 (8 %). Rhinoviruses were most common virus type detected, found in 4/48 (8 %) MEFs. Serotypes included in the current 13-serotype vaccine were detected in only 3/15 (20 %) S. pneumoniae qPCR-positive MEFs. CONCLUSIONS: Bacteria may play an important role in OME, since over 80 % of MEFs contained bacterial NA. Further research into the role of A. otitidis in OME will be helpful. Serotypes of S. pneumoniae not included in the current 13-serotype vaccine may be involved in OME. Larger studies of OME S. pneumoniae serotypes are needed to help determine which additional serotypes should be included in future vaccine formulations in order to try to prevent OME.",2016 Apr 29,"['Slinger, Robert', 'Duval, Melanie', 'Langill, Jonathan', 'Bromwich, Matthew', 'MacCormick, Johnna', 'Chan, Francis', 'Vaccani, Jean-Philippe']",BMC Res Notes,,,True
794b00331ade89870f1475a4c765b8c32ac855b5,PMC,Complete Genome Sequence of Middle East Respiratory Syndrome Coronavirus Isolated from a Dromedary Camel in Egypt,http://dx.doi.org/10.1128/genomeA.00309-16,PMC4850855,27125484,CC BY,We generated the near-full genome sequence of Middle East respiratory syndrome coronavirus (MERS-CoV) from a collected nasal sample of dromedary camel in Egypt. The newly characterized Egyptian strain has high similarity to the previously characterized Egyptian virus and both of viruses fell into a cluster distinct from other MERS-CoVs.,2016 Apr 28,"['Kandeil, Ahmed', 'Shehata, Mahmoud M.', 'El Shesheny, Rabeh', 'Gomaa, Mokhtar R.', 'Ali, Mohamed A.', 'Kayali, Ghazi']",Genome Announc,,,True
9221c3ed344b506c1208f8c2c4f9bf31f60b89da,PMC,“TRP inflammation” relationship in cardiovascular system,http://dx.doi.org/10.1007/s00281-015-0536-y,PMC4851701,26482920,CC BY,"Despite considerable advances in the research and treatment, the precise relationship between inflammation and cardiovascular (CV) disease remains incompletely understood. Therefore, understanding the immunoinflammatory processes underlying the initiation, progression, and exacerbation of many cardiovascular diseases is of prime importance. The innate immune system has an ancient origin and is well conserved across species. Its activation occurs in response to pathogens or tissue injury. Recent studies suggest that altered ionic balance, and production of noxious gaseous mediators link to immune and inflammatory responses with altered ion channel expression and function. Among plausible candidates for this are transient receptor potential (TRP) channels that function as polymodal sensors and scaffolding proteins involved in many physiological and pathological processes. In this review, we will first focus on the relevance of TRP channel to both exogenous and endogenous factors related to innate immune response and transcription factors related to sustained inflammatory status. The emerging role of inflammasome to regulate innate immunity and its possible connection to TRP channels will also be discussed. Secondly, we will discuss about the linkage of TRP channels to inflammatory CV diseases, from a viewpoint of inflammation in a general sense which is not restricted to the innate immunity. These knowledge may serve to provide new insights into the pathogenesis of various inflammatory CV diseases and their novel therapeutic strategies.",2016 Oct 19,"['Numata, Tomohiro', 'Takahashi, Kiriko', 'Inoue, Ryuji']",Semin Immunopathol,,,True
377d9d0d1f580860076b5799e30babd834eda260,PMC,"On Temporal Patterns and Circulation of Influenza Virus Strains in Taiwan, 2008-2014: Implications of 2009 pH1N1 Pandemic",http://dx.doi.org/10.1371/journal.pone.0154695,PMC4854472,27139905,CC BY,"BACKGROUND: It has been observed that, historically, strains of pandemic influenza led to succeeding seasonal waves, albeit with decidedly different patterns. Recent studies suggest that the 2009 A(H1N1)pdm09 pandemic has had an impact on the circulation patterns of seasonal influenza strains in the post-pandemic years. In this work we aim to investigate this issue and also to compare the relative transmissibility of these waves of differing strains using Taiwan influenza surveillance data before, during and after the pandemic. METHODS: We make use of the Taiwan Center for Disease Control and Prevention influenza surveillance data on laboratory-confirmed subtyping of samples and a mathematical model to determine the waves of circulating (and co-circulating) H1, H3 and B virus strains in Taiwan during 2008–2014; or namely, short before, during and after the 2009 pandemic. We further pinpoint the turning points and relative transmissibility of each wave, in order to ascertain whether any temporal pattern exists. RESULTS/FINDINGS: For two consecutive years following the 2009 pandemic, A(H1N1)pdm09 circulated in Taiwan (as in most of Northern Hemisphere), sometimes co-circulating with AH3. From the evolution point of view, A(H1N1)pdm09 and AH3 were able to sustain their circulation patterns to the end of 2010. In fact, A(H1N1)pdm09 virus circulated in six separate waves in Taiwan between summer of 2009 and spring of 2014. Since 2009, a wave of A(H1N1)pmd09 occurred every fall/winter influenza season during our study period except 2011–2012 season, when mainly influenza strain B circulated. In comparing transmissibility, while the estimated per capita weekly growth rates for cumulative case numbers (and the reproduction number) seem to be lower for most of the influenza B waves (0.06~0.26; range of 95% CIs: 0.05~0.32) when compared to those of influenza A, the wave of influenza B from week 8 to week 38 of 2010 immediately following the fall/winter wave of 2009 A(H1N1) pdm09 was substantially higher at r = 0.89 (95% CI: 0.49, 1.28), in fact highest among all the waves detected in this study. Moreover, when AH3 or A(H1N1)pdm09 exhibit high incidence, reported cases of subtype B decreases and vice versa. Further modeling analysis indicated that during the study period, Taiwan nearly experienced at least one wave of influenza epidemic of some strain every summer except in 2012. DISCUSSION: Estimates of R for seasonal influenza are consistent with that of temperate and tropical-subtropical regions, while estimate of R for A(H1N1)pdm09 is comparatively less than countries in Europe and North America, but similar to that of tropical-subtropical regions. This offers indication of regional differences in transmissibility of influenza virus that exists only for pandemic influenza. Despite obvious limitations in the data used, this study, designed to qualitatively compare the temporal patterns and transmissibility of the waves of different strains, illustrates how influenza subtyping data can be utilized to explore the mechanism for various influenza strains to compete or to circulate, to possibly provide predictors of future trends in the evolution of influenza viruses of various subtypes, and perhaps more importantly, to be of use to future annual seasonal influenza vaccine design.",2016 May 3,"['Hsieh, Ying-Hen', 'Huang, Hsiang-Min', 'Lan, Yu-Ching']",PLoS One,,,True
b2f39f20e4e523aab2915f1d22d29d6a29110a20,PMC,Identification of a Peptide Produced by Bifidobacterium longum CECT 7210 with Antirotaviral Activity,http://dx.doi.org/10.3389/fmicb.2016.00655,PMC4855034,27199974,CC BY,"Rotavirus is one of the main causes of acute diarrhea and enteritis in infants. Currently, studies are underway to assess the use of probiotics to improve rotavirus vaccine protection. A previous work demonstrated that the probiotic strain Bifidobacterium longum subsp. infantis CECT 7210 is able to hinder rotavirus replication both in vitro and in vivo. The present study takes a systematic approach in order to identify the molecule directly involved in rotavirus inhibition. Supernatant protease digestions revealed both the proteinaceous nature of the active substance and the fact that the molecule responsible for inhibiting rotavirus replication is released to the supernatant. Following purification by cationic exchange chromatography, active fractions were obtained and the functional compound was identified as an 11-amino acid peptide (MHQPHQPLPPT, named 11-mer peptide) with a molecular mass of 1.282 KDa. The functionality of 11-mer was verified using the synthesized peptide in Wa, Ito, and VA70 rotavirus infections of both HT-29 and MA-104 cell lines. Finally, protease activity was detected in B. longum subsp. infantis CECT 7210 supernatant, which releases 11-mer peptide. A preliminary identification of the protease is also included in the study.",2016 May 4,"['Chenoll, Empar', 'Casinos, Beatriz', 'Bataller, Esther', 'Buesa, Javier', 'Ramón, Daniel', 'Genovés, Salvador', 'Fábrega, Joan', 'Rivero Urgell, Montserrat', 'Moreno Muñoz, José A.']",Front Microbiol,,,True
c4a6612ba3d6a23317a85c42cedd5e6d2f317a9c,PMC,DNA immunization as a technology platform for monoclonal antibody induction,http://dx.doi.org/10.1038/emi.2016.27,PMC4855071,27048742,CC BY,"To combat the threat of many emerging infectious diseases, DNA immunization offers a unique and powerful approach to the production of high-quality monoclonal antibodies (mAbs) against various pathogens. Compared with traditional protein-based immunization approaches, DNA immunization is efficient for testing novel immunogen designs, does not require the production or purification of proteins from a pathogen or the use of recombinant protein technology and is effective at generating mAbs against conformation-sensitive targets. Although significant progress in the use of DNA immunization to generate mAbs has been made over the last two decades, the literature does not contain an updated summary of this experience. The current review provides a comprehensive analysis of the literature, including our own work, describing the use of DNA immunization to produce highly functional mAbs, in particular, those against emerging infectious diseases. Critical factors such as immunogen design, delivery approach, immunization schedule, use of immune modulators and the role of final boost immunization are discussed in detail.",2016 Apr 6,"['Liu, Shuying', 'Wang, Shixia', 'Lu, Shan']",Emerg Microbes Infect,,,True
aa973f2833829b97ebdfd6ce2ac6a29b9100db3a,PMC,Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3,http://dx.doi.org/10.1038/emi.2016.33,PMC4855074,27094905,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) infection has claimed hundreds of lives and has become a global threat since its emergence in Saudi Arabia in 2012. The ability of MERS-CoV to evade the host innate antiviral response may contribute to its severe pathogenesis. Many MERS-CoV-encoded proteins were identified to have interferon (IFN)-antagonizing properties, which correlates well with the reduced IFN levels observed in infected patients and ex vivo models. In this study, we fully characterized the IFN-antagonizing property of the MERS-CoV M protein. Expression of MERS-CoV M protein suppressed type I IFN expression in response to Sendai virus infection or poly(I:C) induction. This suppressive effect was found to be specific for the activation of IFN regulatory factor 3 (IRF3) but not nuclear factor-κB. MERS-CoV M protein interacted with TRAF3 and disrupted TRAF3–TBK1 association leading to reduced IRF3 activation. M proteins from MERS-CoV and SARS-CoV have three highly similar conserved N-terminal transmembrane domains and a C-terminal region. Using chimeric and truncation mutants, the N-terminal transmembrane domains of the MERS-CoV M protein were found to be sufficient for its inhibitory effect on IFN expression, whereas the C-terminal domain was unable to induce this suppression. Collectively, our findings suggest a common and conserved mechanism through which highly pathogenic MERS-CoV and SARS-CoV harness their M proteins to suppress type I IFN expression at the level of TBK1-dependent phosphorylation and activation of IRF3 resulting in evasion of the host innate antiviral response.",2016 Apr 20,"['Lui, Pak-Yin', 'Wong, Lok-Yin Roy', 'Fung, Cheuk-Lai', 'Siu, Kam-Leung', 'Yeung, Man-Lung', 'Yuen, Kit-San', 'Chan, Chi-Ping', 'Woo, Patrick Chiu-Yat', 'Yuen, Kwok-Yung', 'Jin, Dong-Yan']",Emerg Microbes Infect,,,True
d52f0060c0eefc59aa2383d4951125726984fab3,PMC,Intranasal application of polyethyleneimine suppresses influenza virus infection in mice,http://dx.doi.org/10.1038/emi.2016.64,PMC4855075,27118070,CC BY,,2016 Apr 27,"['He, Biao', 'Fu, Yuhong', 'Xia, Shuai', 'Yu, Fei', 'Wang, Qian', 'Lu, Lu', 'Jiang, Shibo']",Emerg Microbes Infect,,,True
9dff93ed512a5e207595d61ad2122f39971e5662,PMC,Intranasal application of polyethyleneimine suppresses influenza virus infection in mice,http://dx.doi.org/10.1038/emi.2016.64,PMC4855075,27118070,CC BY,,2016 Apr 27,"['He, Biao', 'Fu, Yuhong', 'Xia, Shuai', 'Yu, Fei', 'Wang, Qian', 'Lu, Lu', 'Jiang, Shibo']",Emerg Microbes Infect,,,False
576bad43bf08b1a2d302695f5624a77fdbcaf6d0,PMC,"Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission",http://dx.doi.org/10.1038/srep25049,PMC4855236,27142087,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to beta group of coronavirus and was first discovered in 2012. MERS-CoV can infect multiple host species and cause severe diseases in human. We conducted a series of phylogenetic and bioinformatic analyses to study the evolution dynamics of MERS-CoV among different host species with genomic data. Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when MERS-CoV transmitted from their natural host to human; 3) Six out of nine positive selection sites detected in spike (S) protein are located in its receptor-binding domain which is in direct contact with host cells; 4) MERS-CoV frequently transmitted back and forth between human and camel after it had acquired the human-camel infection capability. Together, these results suggest that potential recombination events might have happened frequently during MERS-CoV’s evolutionary history and the positive selection sites in MERS-CoV’s S protein might enable it to infect human.",2016 May 4,"['Zhang, Zhao', 'Shen, Libing', 'Gu, Xun']",Sci Rep,,,True
d82d6db1f132aa8d31e7b5afff09c1679e2dfe4e,PMC,Display of recombinant proteins at the surface of lactic acid bacteria: strategies and applications,http://dx.doi.org/10.1186/s12934-016-0468-9,PMC4855500,27142045,CC BY,"Lactic acid bacteria (LAB) are promising vectors of choice to deliver active molecules to mucosal tissues. They are recognized as safe by the World Health Organization and some strains have probiotic properties. The wide range of potential applications of LAB-driven mucosal delivery includes control of inflammatory bowel disease, vaccine delivery, and management of auto-immune diseases. Because of this potential, strategies for the display of proteins at the surface of LAB are gaining interest. To display a protein at the surface of LAB, a signal peptide and an anchor domain are necessary. The recombinant protein can be attached to the membrane layer, using a transmembrane anchor or a lipoprotein-anchor, or to the cell wall, by a covalent link using sortase mediated anchoring via the LPXTG motif, or by non-covalent liaisons employing binding domains such as LysM or WxL. Both the stability and functionality of the displayed proteins will be affected by the kind of anchor used. The most commonly surfaced exposed recombinant proteins produced in LAB are antigens and antibodies and the most commonly used LAB are lactococci and lactobacilli. Although it is not necessarily so that surface-display is the preferred localization in all cases, it has been shown that for certain applications, such as delivery of the human papillomavirus E7 antigen, surface-display elicits better biological responses, compared to cytosolic expression or secretion. Recent developments include the display of peptides and proteins targeting host cell receptors, for the purpose of enhancing the interactions between LAB and host. Surface-display technologies have other potential applications, such as degradation of biomass, which is of importance for some potential industrial applications of LAB.",2016 May 3,"['Michon, C.', 'Langella, P.', 'Eijsink, V. G. H.', 'Mathiesen, G.', 'Chatel, J. M.']",Microb Cell Fact,,,True
1f534cb2b4a2d3482affcb6d7a1dd23be34f9321,PMC,PER1 prevents excessive innate immune response during endotoxin-induced liver injury through regulation of macrophage recruitment in mice,http://dx.doi.org/10.1038/cddis.2016.9,PMC4855679,27054331,CC BY,"The severity of acute liver failure (ALF) induced by bacterial lipopolysaccharide (LPS) is associated with the hepatic innate immune response. The core circadian molecular clock modulates the innate immune response by controlling rhythmic pathogen recognition by the innate immune system and daily variations in cytokine gene expression. However, the molecular link between circadian genes and the innate immune system has remained unclear. Here, we showed that mice lacking the clock gene Per1 (Period1) are more susceptible to LPS/d-galactosamine (LPS/GalN)-induced macrophage-dependent ALF compared with wild-type (WT) mice. Per1 deletion caused a remarkable increase in the number of Kupffer cells (KCs) in the liver, resulting in an elevation of the levels of pro-inflammatory cytokines after LPS treatment. Loss of Per1 had no effect on the proliferation or apoptosis of macrophages; however, it enhanced the recruitment of macrophages, which was associated with an increase in CC chemokine receptor 2 (Ccr2) expression levels in monocytes/macrophages. Deletion of Ccr2 rescued d-GalN/LPS-induced liver injury in Per1(−/−) mice. We demonstrated that the upregulation of Ccr2 expression by Per1 deletion could be reversed by the synthetic peroxisome proliferator-activated receptor gamma (PPAR-γ) antagonist GW9662. Further analysis indicated that PER1 binds to PPAR-γ on the Ccr2 promoter and enhanced the inhibitory effect of PPAR-γ on Ccr2 expression. These results reveal that Per1 reduces hepatic macrophage recruitment through interaction with PPAR-γ and prevents an excessive innate immune response in endotoxin-induced liver injury.",2016 Apr 7,"['Wang, T', 'Wang, Z', 'Yang, P', 'Xia, L', 'Zhou, M', 'Wang, S', 'Du, Jie', 'Zhang, J']",Cell Death Dis,,,True
7fdea1d57d5d3d0ee393379c8437b0393f0ce542,PMC,"Epithelial cell lines of the cotton rat (Sigmodon hispidus) are highly susceptible in vitro models to zoonotic Bunya-, Rhabdo-, and Flaviviruses",http://dx.doi.org/10.1186/s12985-016-0531-5,PMC4855710,27142375,CC BY,"BACKGROUND: Small mammals such as bats and rodents have been increasingly recognized as reservoirs of novel potentially zoonotic pathogens. However, few in vitro model systems to date allow assessment of zoonotic viruses in a relevant host context. The cotton rat (Sigmodon hispidus) is a New World rodent species that has a long-standing history as an experimental animal model due to its unique susceptibility to human viruses. Furthermore, wild cotton rats are associated with a large variety of known or potentially zoonotic pathogens. METHODS: A method for the isolation and culture of airway epithelial cell lines recently developed for bats was applied for the generation of rodent airway and renal epithelial cell lines from the cotton rat. Continuous cell lines were characterized for their epithelial properties as well as for their interferon competence. Susceptibility to members of zoonotic Bunya-, Rhabdo-, and Flaviviridae, in particular Rift Valley fever virus (RVFV), vesicular stomatitis virus (VSV), West Nile virus (WNV), and tick-borne encephalitis virus (TBEV) was tested. Furthermore, novel arthropod-derived viruses belonging to the families Bunya-, Rhabdo-, and Mesoniviridae were tested. RESULTS: We successfully established airway and kidney epithelial cell lines from the cotton rat, and characterized their epithelial properties. Cells were shown to be interferon-competent. Viral infection assays showed high-titre viral replication of RVFV, VSV, WNV, and TBEV, as well as production of infectious virus particles. No viral replication was observed for novel arthropod-derived members of the Bunya-, Rhabdo-, and Mesoniviridae families in these cell lines. CONCLUSION: In the current study, we showed that newly established cell lines from the cotton rat can serve as host-specific in vitro models for viral infection experiments. These cell lines may also serve as novel tools for virus isolation, as well as for the investigation of virus-host interactions in a relevant host species.",2016 May 4,"['Ehlen, Lukas', 'Tödtmann, Jan', 'Specht, Sabine', 'Kallies, René', 'Papies, Jan', 'Müller, Marcel A.', 'Junglen, Sandra', 'Drosten, Christian', 'Eckerle, Isabella']",Virol J,,,True
10f87d75360ca119636fcd75da502bcb0bf7845d,PMC,Qualitative study on the shifting sociocultural meanings of the facemask in Hong Kong since the severe acute respiratory syndrome (SARS) outbreak: implications for infection control in the post-SARS era,http://dx.doi.org/10.1186/s12939-016-0358-0,PMC4855818,27145823,CC BY,"BACKGROUND: The clinical importance and efficacy of facemasks in infection prevention have been documented in the international literature. Past studies have shown that the perceived susceptibility, the perceived severity of being afflicted with life-threatening diseases, and the perceived benefits of using a facemask are predictors of a person’s use of a facemask. However, I argue that people wear a facemask not merely for infection prevention, and various sociocultural reasons have been motivating people to wear (and not wear) a facemask. Facemasks thus have sociocultural implications for people. Research on the sociocultural meanings of facemasks is scant, and even less is known on how the shifting sociocultural meanings of facemasks are related to the changing social environment, which, I argue, serve as remarkable underlying factors for people using (and not using) facemasks. As new infectious diseases such as avian influenza and Middle East Respiratory Syndrome have been emerging, threatening people’s health worldwide, and because facemasks have been documented to have substantial efficacy in the prevention of infection transmission, understanding the sociocultural meanings of facemasks has significant implications for public health policymakers and health care providers in designing a socially and culturally responsive public health and infection control policy for the community. METHODS: A qualitative research design involving the use of 40 individual, in-depth semistructured interviews and a phenomenological analysis approach were adopted. RESULTS: The sociocultural meanings of the facemask have been undergoing constant change, from positive to negative, which resulted in the participants displaying hesitation in using a facemask in the post-SARS era. Because it represents a violation of societal ideologies and traditional Chinese cultural beliefs, the meanings of the facemask that had developed during the SARS outbreak failed to be sustained in the post-SARS era. CONCLUSION: The changes in meaning not only influenced the participants’ perceptions of the facemask but also influenced their perceptions of people who use facemasks, which ultimately influenced their health behavior, preventing them from using facemasks in the post-SARS era. These findings have critical implications for designing a culturally responsive infection prevention and facemask usage policy in the future.",2016 May 4,"Siu, Judy Yuen-man",Int J Equity Health,,,True
1e2493a8e26be4ff934b96dedc32dc7cf5728370,PMC,Trigger factor assisted soluble expression of recombinant spike protein of porcine epidemic diarrhea virus in Escherichia coli,http://dx.doi.org/10.1186/s12896-016-0268-7,PMC4855837,27142206,CC BY,"BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of swine. The spike glycoprotein (S) of PEDV is the major immunogenic determinant that plays a pivotal role in the induction of neutralizing antibodies against PEDV, which therefore is an ideal target for the development of subunit vaccine. In an attempt to develop a subunit vaccine for PEDV, we cloned two different fragments of S protein and expressed as glutathione S-transferase (GST)-tagged fusion proteins, namely rGST-COE and rGST-S1D, in E.coli. However, the expression of these recombinant protein antigens using a variety of expression vectors, strains, and induction conditions invariably resulted in inclusion bodies. To achieve the soluble expression of recombinant proteins, several chaperone co-expression systems were tested in this study. RESULTS: We firstly tested various chaperone co-expression systems and found that co-expression of trigger factor (TF) with recombinant proteins at 15 °C was most useful in soluble production of rGST-COE and rGST-S1D compared to GroEL-ES and DnaK-DnaJ-GrpE/GroEL-ES systems. The soluble rGST-COE and rGST-S1D were purified using glutathione Sepharose 4B with a yield of 7.5 mg/l and 5 mg/l, respectively. Purified proteins were detected by western blot using mouse anti-GST mAb and pig anti-PEDV immune sera. In an indirect ELISA, purified proteins showed immune reactivity with pig anti-PEDV immune sera. Finally, immunization of mice with 10 μg of purified proteins elicited highly potent serum IgG and serum neutralizing antibody titers. CONCLUSIONS: In this study, soluble production of recombinant spike protein of PEDV, rGST-COE and rGST-S1D, were achieved by using TF chaperone co-expression system. Our results suggest that soluble rGST-COE and rGST-S1D produced by co-expressing chaperones may have the potential to be used as subunit vaccine antigens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12896-016-0268-7) contains supplementary material, which is available to authorized users.",2016 May 4,"['Piao, Da-Chuan', 'Shin, Do-Woon', 'Kim, In-Seon', 'Li, Hui-Shan', 'Oh, Seo-Ho', 'Singh, Bijay', 'Maharjan, S.', 'Lee, Yoon-Seok', 'Bok, Jin-Duck', 'Cho, Chong-Su', 'Hong, Zhong-Shan', 'Kang, Sang-Kee', 'Choi, Yun-Jaie']",BMC Biotechnol,,,True
ceab18d97f09ef0d9030f0c808f7ab5ab1c7d583,PMC,NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap(4)A) and Down-Regulates Immune Response and Cancer Promotion Genes,http://dx.doi.org/10.1371/journal.pone.0154674,PMC4856261,27144453,CC BY,"Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap(4)A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap(4)A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap(4)A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity(®) Pathway Analysis (IPA(®)) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA(®) for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap(4)A and/or NUDT2 disruption include binding of Ap(4)A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap(4)A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap(4)A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis.",2016 May 4,"['Marriott, Andrew S.', 'Vasieva, Olga', 'Fang, Yongxiang', 'Copeland, Nikki A.', 'McLennan, Alexander G.', 'Jones, Nigel J.']",PLoS One,,,True
58086bd6aa7a845eac58001de931144a3cebd644,PMC,Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity,http://dx.doi.org/10.1038/srep25359,PMC4857172,27146253,CC BY,"Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.",2016 May 5,"['Min, Chan-Ki', 'Cheon, Shinhye', 'Ha, Na-Young', 'Sohn, Kyung Mok', 'Kim, Yuri', 'Aigerim, Abdimadiyeva', 'Shin, Hyun Mu', 'Choi, Ji-Yeob', 'Inn, Kyung-Soo', 'Kim, Jin-Hwan', 'Moon, Jae Young', 'Choi, Myung-Sik', 'Cho, Nam-Hyuk', 'Kim, Yeon-Sook']",Sci Rep,,,True
ce374c50076cc3e74a12e5b910cae08d2fe543ba,PMC,Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity,http://dx.doi.org/10.1038/srep25359,PMC4857172,27146253,CC BY,"Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.",2016 May 5,"['Min, Chan-Ki', 'Cheon, Shinhye', 'Ha, Na-Young', 'Sohn, Kyung Mok', 'Kim, Yuri', 'Aigerim, Abdimadiyeva', 'Shin, Hyun Mu', 'Choi, Ji-Yeob', 'Inn, Kyung-Soo', 'Kim, Jin-Hwan', 'Moon, Jae Young', 'Choi, Myung-Sik', 'Cho, Nam-Hyuk', 'Kim, Yeon-Sook']",Sci Rep,,,False
5d9e52011787ca962e5391dd027c6641a37f9cba,PMC,"Survival functions for defining a clinical management Lost To Follow-Up (LTFU) cut-off in Antiretroviral Therapy (ART) program in Zomba, Malawi",http://dx.doi.org/10.1186/s12911-016-0290-7,PMC4857410,27150958,CC BY,"BACKGROUND: While, lost to follow-up (LTFU) from antiretroviral therapy (ART) can be considered a catch-all category for patients who miss scheduled visits or medication pick-ups, operational definitions and methods for defining LTFU vary making comparisons across programs challenging. Using weekly cut-offs, we sought to determine the probability that an individual would return to clinic given that they had not yet returned in order to identify the LTFU cut-off that could be used to inform clinical management and tracing procedures. METHODS: Individuals who initiated ART with Dignitas International supported sites (n = 22) in Zomba, Malawi between January 1 2007-June 30 2010 and were ≥ 1 week late for a follow-up visit were included. Lateness was categorized using weekly cut-offs from ≥1 to ≥26 weeks late. At each weekly cut-off, the proportion of patients who returned for a subsequent follow-up visit were identified. Cumulative Distribution Functions (CDFs) were plotted to determine the probability of returning as a function of lateness. Hazard functions were plotted to demonstrate the proportion of patients who returned each weekly interval relative to those who had yet to return. RESULTS: In total, n = 4484 patients with n = 7316 follow-up visits were included. The number of included follow-up visits per patient ranged from 1–10 (median: 1). Both the CDF and hazard function demonstrated that after being ≥9 weeks late, the proportion of new patients who returned relative to those who had yet to return decreased substantially. CONCLUSIONS: We identified a LTFU definition useful for clinical management. The simple functions plotted here did not require advanced statistical expertise and were created using Microsoft Excel, making it a particularly practical method for HIV programs in resource-constrained settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12911-016-0290-7) contains supplementary material, which is available to authorized users.",2016 May 5,"['Rachlis, Beth', 'Cole, Donald C.', 'van Lettow, Monique', 'Escobar, Michael']",BMC Med Inform Decis Mak,,,True
5edd56f96660760a5f8ae69efd7d9e976a00c4ee,PMC,Immunogenicity of Virus Like Particle Forming Baculoviral DNA Vaccine against Pandemic Influenza H1N1,http://dx.doi.org/10.1371/journal.pone.0154824,PMC4858234,27149064,CC BY,"An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA). However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV) envelope-coated, baculovirus-based, virus-like-particle (VLP)–forming DNA vaccine (termed AcHERV-VLP) against pandemic influenza A/California/04/2009 (pH1N1). BALB/c mice immunized with AcHERV-VLP (1×10(7) FFU AcHERV-VLP, i.m.) and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8), elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines.",2016 May 5,"['Gwon, Yong-Dae', 'Kim, Sehyun', 'Cho, Yeondong', 'Heo, Yoonki', 'Cho, Hansam', 'Park, Kihoon', 'Lee, Hee-Jung', 'Choi, Jiwon', 'Poo, Haryoung', 'Kim, Young Bong']",PLoS One,,,True
106b81593063e1df0817b8ca2e0a90823003201d,PMC,Immunogenicity of Virus Like Particle Forming Baculoviral DNA Vaccine against Pandemic Influenza H1N1,http://dx.doi.org/10.1371/journal.pone.0154824,PMC4858234,27149064,CC BY,"An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA). However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV) envelope-coated, baculovirus-based, virus-like-particle (VLP)–forming DNA vaccine (termed AcHERV-VLP) against pandemic influenza A/California/04/2009 (pH1N1). BALB/c mice immunized with AcHERV-VLP (1×10(7) FFU AcHERV-VLP, i.m.) and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8), elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines.",2016 May 5,"['Gwon, Yong-Dae', 'Kim, Sehyun', 'Cho, Yeondong', 'Heo, Yoonki', 'Cho, Hansam', 'Park, Kihoon', 'Lee, Hee-Jung', 'Choi, Jiwon', 'Poo, Haryoung', 'Kim, Young Bong']",PLoS One,,,True
275dd71da13e09fcace07d5824ac14a2c38d1df1,PMC,The 2014–2015 Ebola outbreak in West Africa: Hands On,http://dx.doi.org/10.1186/s13756-016-0112-9,PMC4858848,,CC BY,"The International Consortium for Prevention and Infection Control (ICPIC) organises a biannual conference (ICPIC) on various subjects related to infection prevention, treatment and control. During ICPIC 2015, held in Geneva in June 2015, a full one-day session focused on the 2014–2015 Ebola virus disease (EVD) outbreak in West Africa. This article is a non-exhaustive compilation of these discussions. It concentrates on lessons learned and imagining a way forward for the communities most affected by the epidemic. The reader can access video recordings of all lectures delivered during this one-day session, as referenced. Topics include the timeline of the international response, linkages between the dynamics of the epidemic and infection prevention and control, the importance of community engagement, and updates on virology, diagnosis, treatment and vaccination issues. The paper also includes discussions from public health, infectious diseases, critical care and infection control experts who cared for patients with EVD in Africa, in Europe, and in the United Sates and were involved in Ebola preparedness in both high- and low-resource settings and countries. This review concludes that too little is known about the pathogenesis and treatment of EVD, therefore basic and applied research in this area are urgently required. Furthermore, it is clear that epidemic preparedness needs to improve globally, in particular through the strengthening of health systems at local and national levels. There is a strong need for culturally sensitive approaches to public health which could be designed and delivered by social scientists and medical professionals working together. As of December 2015, this epidemic killed more than 11,000 people and infected more than 28,000; it has also generated more than 17,000 survivors and orphans, many of whom face somatic and psychological complications. The continued treatment and rehabilitation of these people is a public health priority, which also requires an integration of specific medical and social science approaches, not always available in West Africa.",2016 May 5,"['Vetter, Pauline', 'Dayer, Julie-Anne', 'Schibler, Manuel', 'Allegranzi, Benedetta', 'Brown, Donal', 'Calmy, Alexandra', 'Christie, Derek', 'Eremin, Sergey', 'Hagon, Olivier', 'Henderson, David', 'Iten, Anne', 'Kelley, Edward', 'Marais, Frederick', 'Ndoye, Babacar', 'Pugin, Jérôme', 'Robert-Nicoud, Hugues', 'Sterk, Esther', 'Tapper, Michael', 'Siegrist, Claire-Anne', 'Kaiser, Laurent', 'Pittet, Didier']",Antimicrob Resist Infect Control,,,True
eaba1af19b87795dc237a55c0236d89ede3cf46a,PMC,"Isolation and identification of group A rotaviruses among neonatal diarrheic calves, Morocco",http://dx.doi.org/10.1186/s13104-016-2065-8,PMC4858901,27150259,CC BY,"BACKGROUND: Group A rotaviruses (RVA) are the main cause of neonatal calve diarrhea (NCD) in Morocco. In this study, we isolated RVA strains from NCD clinical samples in order to support RVA disease control in Morocco. This isolation process constitutes a first step toward vaccine development. METHODS: Thirteen fecal samples were obtained from calves with a single episode of neonate calf diarrhea at three different dairies and two samples were collected from field during a severe NCD outbreak. Diagnosis of RVA infection was based on fecal immune-chromatographic rapid test and further evaluated for their hemagglutination (HA) activity. RVA isolation was carried out on MA104 cells after inoculates were treated with different concentrations of trypsin TPCK. All RVA isolates were confirmed by LSI VetMAX™ Triplex Ruminant Rotavirus & Coronavirus Real-Time PCR kit. G and P typing were determined by direct sequencing of the VP4 and VP7 amplicons. RESULTS: RVA isolation was achieved for nine clinical samples following one or two passages (60 %) and was properly depended on HA activity and trypsin treatment of inoculates. The first sign of CPE detected consisted of increased cell granularity, obscure cell boundaries, cell rounding, and eventual degeneration and detachment of cells. At lower TPCK concentration (3–10 μg/inoculum), no changes at the cellular level were observed, while cells activated with 25–30 μg of trypsin/inoculums, they degenerated and trypsin cytotoxicity was enhanced. Appreciable changes in cell’s morphology were detected with optimal trypsin concentration of 15–20 μg trypsin/inoculums. Data from qRT-PCR confirmed that unsuccessful cultivations have No-Ct, and all nine isolates have Ct values ranged between 12.17 and 24.69. Analysis sequencing revealed that field isolates were of G6 P[5] serotype and isolates from the dairy NCD samples were of G10 P[14] serotype. CONCLUSIONS: To our knowledge, this is the first study in Morocco which reports the circulation of G10P[14] in NCD on dairy farms and G6P[5] in the field. Our study constitutes a crucial and a necessary step allowing preventive and veterinary medicine to support RVA disease controls in the country.",2016 May 5,"['Ennima, Imane', 'Sebbar, Ghizlane', 'Harif, Bachir', 'Amzazi, Saaid', 'Loutfi, Chafiqa', 'Touil, Nadia']",BMC Res Notes,,,True
53d4dd6acd3501c47b364dbae1ba3dd2083b895a,PMC,Presentation and outcome of Middle East respiratory syndrome in Saudi intensive care unit patients,http://dx.doi.org/10.1186/s13054-016-1303-8,PMC4859954,27153800,CC BY,"BACKGROUND: Middle East respiratory syndrome coronavirus infection is associated with high mortality rates but limited clinical data have been reported. We describe the clinical features and outcomes of patients admitted to an intensive care unit (ICU) with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. METHODS: Retrospective analysis of data from all adult (>18 years old) patients admitted to our 20-bed mixed ICU with Middle East respiratory syndrome coronavirus infection between October 1, 2012 and May 31, 2014. Diagnosis was confirmed in all patients using real-time reverse transcription polymerase chain reaction on respiratory samples. RESULTS: During the observation period, 31 patients were admitted with MERS-CoV infection (mean age 59 ± 20 years, 22 [71 %] males). Cough and tachypnea were reported in all patients; 22 (77.4 %) patients had bilateral pulmonary infiltrates. Invasive mechanical ventilation was applied in 27 (87.1 %) and vasopressor therapy in 25 (80.6 %) patients during the intensive care unit stay. Twenty-three (74.2 %) patients died in the ICU. Nonsurvivors were older, had greater APACHE II and SOFA scores on admission, and were more likely to have received invasive mechanical ventilation and vasopressor therapy. After adjustment for the severity of illness and the degree of organ dysfunction, the need for vasopressors was an independent risk factor for death in the ICU (odds ratio = 18.33, 95 % confidence interval: 1.11–302.1, P = 0.04). CONCLUSIONS: MERS-CoV infection requiring admission to the ICU is associated with high morbidity and mortality. The need for vasopressor therapy is the main risk factor for death in these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1303-8) contains supplementary material, which is available to authorized users.",2016 May 7,"['Almekhlafi, Ghaleb A.', 'Albarrak, Mohammed M.', 'Mandourah, Yasser', 'Hassan, Sahar', 'Alwan, Abid', 'Abudayah, Abdullah', 'Altayyar, Sultan', 'Mustafa, Mohamed', 'Aldaghestani, Tareef', 'Alghamedi, Adnan', 'Talag, Ali', 'Malik, Muhammad K.', 'Omrani, Ali S.', 'Sakr, Yasser']",Crit Care,,,True
3d09812aba24146255e664c9ed4ed7d5dcd9e3b3,PMC,Dengue research: a bibliometric analysis of worldwide and Arab publications during 1872–2015,http://dx.doi.org/10.1186/s12985-016-0534-2,PMC4859974,27154247,CC BY,"BACKGROUND: Dengue is an important emerging and re-emerging arboviral infection globally as a rapidly growing and widespread public health problem, with transmission occurring in more than 128 countries in Asia, Americas, southeast Africa, western Pacific, and eastern Mediterranean regions. Therefore, the aim of this study was to characterize and quantify the scientific output of dengue research in Arab countries relative to that worldwide by using a bibliometric analysis. METHODS: The standardized search approach based on the use of the the keyword “dengue” in the title, abstract, and keyword field was used to get research output related to dengue at a global level. All data related to dengue were collected from the past to December 31, 2015. RESULTS: A total of 19,581 dengue-related documents identified in the Scopus database. The results show that the study of dengue exhibits an overall upward trend from 1872 to 2015 with peak publications in 2014. The leading countries in dengue research were the USA (4,709; 24.05 %), India (1,942; 9.92 %), Brazil (1,530; 7.81 %), Thailand (1,260; 6.43 %), the UK (1,129; 5.77 %), and France (1,087; 5.55 %). Only 226 (1.16 % of the overall global research effort in the dengue field) articles were published from the Arab region. The total number of citations for all publications was 352,710, with an average of 18.0 citations per publication. Furthermore, the h-index for all extracted data related to dengue research was 186. Kingdom of Saudi Arabia (KSA) was the most productive country in Arab region with 102 documents representing 45.1 %. Furthermore, the h-index for all extracted data related to dengue research was 27. The USA was Arab’s most main cooperative partner (46, 20.4 %), followed by India (36, 15.9 %). CONCLUSIONS: The amount of literature related to dengue research has considerably increased over the last decade. This bibliometric analysis has demonstrated the leading role that the USA, India, Brazil, Thailand, the UK, and France play in dengue research. The Arab world produced fewer publications related to dengue with lower quality than other world countries.",2016 May 6,"Zyoud, Sa’ed H.",Virol J,,,True
83c33f01d7a8c1abca6dedf7e12e485fc7ed6ed3,PMC,Cortex phellodendri Extract Relaxes Airway Smooth Muscle,http://dx.doi.org/10.1155/2016/8703239,PMC4863113,27239213,CC BY,"Cortex phellodendri is used to reduce fever and remove dampness and toxin. Berberine is an active ingredient of C. phellodendri. Berberine from Argemone ochroleuca can relax airway smooth muscle (ASM); however, whether the nonberberine component of C. phellodendri has similar relaxant action was unclear. An n-butyl alcohol extract of C. phellodendri (NBAECP, nonberberine component) was prepared, which completely inhibits high K(+)- and acetylcholine- (ACH-) induced precontraction of airway smooth muscle in tracheal rings and lung slices from control and asthmatic mice, respectively. The contraction induced by high K(+) was also blocked by nifedipine, a selective blocker of L-type Ca(2+) channels. The ACH-induced contraction was partially inhibited by nifedipine and pyrazole 3, an inhibitor of TRPC3 and STIM/Orai channels. Taken together, our data demonstrate that NBAECP can relax ASM by inhibiting L-type Ca(2+) channels and TRPC3 and/or STIM/Orai channels, suggesting that NBAECP could be developed to a new drug for relieving bronchospasm.",2016 Apr 27,"['Jiang, Qiu-Ju', 'Chen, Weiwei', 'Dan, Hong', 'Tan, Li', 'Zhu, He', 'Yang, Guangzhong', 'Shen, Jinhua', 'Peng, Yong-Bo', 'Zhao, Ping', 'Xue, Lu', 'Yu, Meng-Fei', 'Ma, Liqun', 'Si, Xiao-Tang', 'Wang, Zhuo', 'Dai, Jiapei', 'Qin, Gangjian', 'Zou, Chunbin', 'Liu, Qing-Hua']",Evid Based Complement Alternat Med,,,True
fb775c4af00b99294d4e8812a3f23ba6aca32774,PMC,Discovery of a Novel Bat Gammaherpesvirus,http://dx.doi.org/10.1128/mSphere.00016-16,PMC4863598,27303690,CC BY,"Zoonosis is the leading cause of emerging infectious diseases. In a recent article, R. S. Shabman et al. (mSphere 1[1]:e00070-15, 2016, http://dx.doi.org/10.1128/mSphere.00070-15) report the identification of a novel gammaherpesvirus in a cell line derived from the microbat Myotis velifer incautus. This is the first report on a replicating, infectious gammaherpesvirus from bats. The new virus is named bat gammaherpesvirus 8 (BGHV8), also known as Myotis gammaherpesvirus 8, and is able to infect multiple cell lines, including those of human origin. Using next-generation sequencing technology, the authors constructed a full-length annotated genomic map of BGHV8. Phylogenetic analysis of several genes from BGHV8 revealed similarity to several mammalian gammaherpesviruses, including Kaposi’s sarcoma-associated herpesvirus (KSHV).",2016 Feb 17,"['Host, Kurtis M.', 'Damania, Blossom']",mSphere,,,True
6b58f76c98afb6435969ef4d9f9a063058265b98,PMC,Isolation and Characterization of a Novel Gammaherpesvirus from a Microbat Cell Line,http://dx.doi.org/10.1128/mSphere.00070-15,PMC4863610,27303702,CC BY,"While employing deep sequencing and de novo assembly to characterize the mRNA transcript profile of a cell line derived from the microbat Myotis velifer incautus, we serendipitously identified mRNAs encoding proteins with a high level of identity to herpesviruses. A majority were closely related to proteins of equine herpesvirus 2 (EHV-2), a horse gammaherpesvirus. We demonstrated by electron microscopy the presence of herpesvirus-like particles in the microbat cells. Passage of supernatants from microbat cells to Vero cells resulted in syncytium formation, and expression of viral genes and amplification of viral DNA were demonstrated by quantitative PCR. Susceptibility of human cell lines to productive infection was also demonstrated. Next-generation sequencing and de novo assembly of the viral genome from supernatants from Vero cells yielded a single contig of approximately 130 kb with at least 77 open reading frames (ORFs), predicted microRNAs (miRNAs), and a gammaherpesvirus genomic organization. Phylogenic analysis of the envelope glycoprotein (gB) and DNA polymerase (POLD1) revealed similarity to multiple gammaherpesviruses, including those from as-yet-uncultured viruses of the Rhadinovirus genus that were obtained by deep sequencing of bat tissues. Moreover, the assembled genome revealed ORFs that share little or no homology to known ORFs in EHV-2 but are similar to accessory proteins of other gammaherpesviruses. Some also have striking homology to predicted Myotis bat proteins. Cumulatively, this study provides the first isolation and characterization of a replication-competent bat gammaherpesvirus. IMPORTANCE Bats are of significant interest as reservoirs for zoonotic viral pathogens; however, tools to dissect bat-virus interactions are limited in availability. This study serendipitously identified, in an established bat cell line, a fully replication-competent gammaherpesvirus; determined the complete genome sequence of the virus; and generated a viral transcript map. This virus can replicate in select human and nonhuman primate cell lines. However, analyses of viral sequences support a bat origin for this virus; we therefore refer to the virus as bat gammaherpesvirus 8 (BGHV8). The viral genome contains unique open reading frames that likely encode modulators of bat innate and adaptive immune signaling pathways and expresses viral miRNAs. The virus and its gene products should provide a unique tool to dissect both bat and gammaherpesvirus biology.",2016 Feb 17,"['Shabman, Reed S.', 'Shrivastava, Susmita', 'Tsibane, Tshidi', 'Attie, Oliver', 'Jayaprakash, Anitha', 'Mire, Chad E.', 'Dilley, Kari E.', 'Puri, Vinita', 'Stockwell, Timothy B.', 'Geisbert, Thomas W.', 'Sachidanandam, Ravi', 'Basler, Christopher F.']",mSphere,,,True
e6e00bfca850f42e1b2baa9ce190d37554f4a42e,PMC,Genome Sequencing and Analysis of Catopsilia pomona nucleopolyhedrovirus: A Distinct Species in Group I Alphabaculovirus,http://dx.doi.org/10.1371/journal.pone.0155134,PMC4864199,27166956,CC BY,"The genome sequence of Catopsilia pomona nucleopolyhedrovirus (CapoNPV) was determined by the Roche 454 sequencing system. The genome consisted of 128,058 bp and had an overall G+C content of 40%. There were 130 hypothetical open reading frames (ORFs) potentially encoding proteins of more than 50 amino acids and covering 92% of the genome. Among all the hypothetical ORFs, 37 baculovirus core genes, 23 lepidopteran baculovirus conserved genes and 10 genes conserved in Group I alphabaculoviruses were identified. In addition, the genome included regions of 8 typical baculoviral homologous repeat sequences (hrs). Phylogenic analysis showed that CapoNPV was in a distinct branch of clade “a” in Group I alphabaculoviruses. Gene parity plot analysis and overall similarity of ORFs indicated that CapoNPV is more closely related to the Group I alphabaculoviruses than to other baculoviruses. Interesting, CapoNPV lacks the genes encoding the fibroblast growth factor (fgf) and ac30, which are conserved in most lepidopteran and Group I baculoviruses, respectively. Sequence analysis of the F-like protein of CapoNPV showed that some amino acids were inserted into the fusion peptide region and the pre-transmembrane region of the protein. All these unique features imply that CapoNPV represents a member of a new baculovirus species.",2016 May 11,"['Wang, Jun', 'Zhu, Zheng', 'Zhang, Lei', 'Hou, Dianhai', 'Wang, Manli', 'Arif, Basil', 'Kou, Zheng', 'Wang, Hualin', 'Deng, Fei', 'Hu, Zhihong']",PLoS One,,,True
345a04a8633d593b5a400b559d533a6b4595f490,PMC,Comparative Transcriptome Analysis of Bombyx mori (Lepidoptera) Larval Midgut Response to BmNPV in Susceptible and Near-Isogenic Resistant Strains,http://dx.doi.org/10.1371/journal.pone.0155341,PMC4864234,27168061,CC BY,"Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the primary pathogens causing severe economic losses in sericulture. However, the molecular mechanism of silkworm resistance to BmNPV remains largely unknown. Here, the recurrent parent P50 (susceptible strain) and the near-isogenic line BC9 (resistance strain) were used in a comparative transcriptome study examining the response to infection with BmNPV. A total of 14,300 unigenes were obtained from two different resistant strains; of these, 869 differentially expressed genes (DEGs) were identified after comparing the four transcriptomes. Many DEGs associated with protein metabolism, cytoskeleton, and apoptosis may be involved in the host response to BmNPV infection. Moreover, some immunity related genes were also altered following BmNPV infection. Specifically, after removing genetic background and individual immune stress response genes, 22 genes were found to be potentially involved in repressing BmNPV infection. These genes were related to transport, virus replication, intracellular innate immune, and apoptosis. Our study provided an overview of the molecular mechanism of silkworm resistance to BmNPV infection and laid a foundation for controlling BmNPV in the future.",2016 May 11,"['Wang, Xue-Yang', 'Yu, Hai-Zhong', 'Geng, Lei', 'Xu, Jia-Ping', 'Yu, Dong', 'Zhang, Shang-Zhi', 'Ma, Yan', 'Fei, Dong-Qiong']",PLoS One,,,True
9da90a751f76421e3069d40bd2eae1891f778965,PMC,Correction: Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor,http://dx.doi.org/10.1371/journal.ppat.1005650,PMC4864313,27166862,CC BY,,2016 May 11,"['Kim, Yunjeong', 'Liu, Hongwei', 'Kankanamalage, Anushka C. Galasiti', 'Weerasekara, Sahani', 'Hua, Duy H.', 'Groutas, William C.', 'Chang, Kyeong-Ok', 'Pedersen, Niels C.']",PLoS Pathog,,,False
87d031191cd30614cfded9fbea64d0a4db44952a,PMC,Neurological Complications of Middle East Respiratory Syndrome Coronavirus: A Report of Two Cases and Review of the Literature,http://dx.doi.org/10.1155/2016/3502683,PMC4864560,27239356,CC BY,"Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was first discovered in September 2012 in Saudi Arabia. Since then, it caused more than 1600 laboratory-confirmed cases and more than 580 deaths among them. The clinical course of the disease ranges from asymptomatic infection to severe lower respiratory tract illness with multiorgan involvement and death. The disease can cause pulmonary, renal, hematological, and gastrointestinal complications. In this paper, we report neurological complications of MERS-CoV in two adult patients, and we hypothesize the pathophysiology. The first patient had an intracerebral hemorrhage as a result of thrombocytopenia, disseminated intravascular coagulation, and platelet dysfunction. The second case was a case of critical illness polyneuropathy complicating a long ICU stay. In these cases, the neurological complications were secondary to systemic complications and long ICU stay. Autopsy studies are needed to further understand the pathological mechanism.",2016 Apr 28,"['Algahtani, Hussein', 'Subahi, Ahmad', 'Shirah, Bader']",Case Rep Neurol Med,,,True
530fba50d0d6378e080e760093969b0b3b9c479d,PMC,Influence of the Pressure Difference and Door Swing on Heavy Contaminants Migration between Rooms,http://dx.doi.org/10.1371/journal.pone.0155159,PMC4865048,27171260,CC BY,"This paper presents the results of investigations whose aim was to describe the influence of the pressure difference level on the ability of contaminants migration between neighbouring rooms in dynamic conditions associated with door swing. The analysis was based on airflow visualization made with cold smoke, which simulated the heavy contaminants. The test room was pressurized to a specific level and then the door was opened to observe the trail of the smoke plume in the plane of the door. The door was opened in both directions: to the positively and negatively pressurized room. This study focuses on the visualization of smoke plume discharge and an uncertainty analysis is not applicable. Unlike other studies which focus on the analysis of pressure difference, the present study looks at the contaminants which are heavier than air and on “pumping out” the contaminants by means of door swing. Setting the proper level of pressure difference between the contaminated room and the neighbouring rooms can prove instrumental in ensuring protection against toxic contaminants migration. This study helped to establish the threshold of pressure difference necessary to reduce migration of heavy contaminants to neighbouring rooms.",2016 May 12,"['Hendiger, Jacek', 'Chludzińska, Marta', 'Ziętek, Piotr']",PLoS One,,,True
8e875cc9628872c52aea9d9c298e1b87cf82f1e7,PMC,"The Role of Human Coronaviruses in Children Hospitalized for Acute Bronchiolitis, Acute Gastroenteritis, and Febrile Seizures: A 2-Year Prospective Study",http://dx.doi.org/10.1371/journal.pone.0155555,PMC4865086,27171141,CC BY,"Human coronaviruses (HCoVs) are associated with a variety of clinical presentations in children, but their role in disease remains uncertain. The objective of our prospective study was to investigate HCoVs associations with various clinical presentations in hospitalized children up to 6 years of age. Children hospitalized with acute bronchiolitis (AB), acute gastroenteritis (AGE), or febrile seizures (FS), and children admitted for elective surgical procedures (healthy controls) were included in the study. In patients with AB, AGE, and FS, a nasopharyngeal (NP) swab and blood sample were obtained upon admission and the follow-up visit 14 days later, whereas in children with AGE a stool sample was also acquired upon admission; in healthy controls a NP swab and stool sample were taken upon admission. Amplification of polymerase 1b gene was used to detect HCoVs in the specimens. HCoVs-positive specimens were also examined for the presence of several other viruses. HCoVs were most often detected in children with FS (19/192, 9.9%, 95% CI: 6–15%), followed by children with AGE (19/218, 8.7%, 95% CI: 5.3–13.3%) and AB (20/308, 6.5%, 95% CI: 4.0–9.8%). The presence of other viruses was a common finding, most frequent in the group of children with AB (19/20, 95%, 95% CI: 75.1–99.8%), followed by FS (10/19, 52.6%, 95% CI: 28.9–75.6%) and AGE (7/19, 36.8%, 95% CI: 16.3–61.6%). In healthy control children HCoVs were detected in 3/156 (1.9%, 95% CI: 0.4–5.5%) NP swabs and 1/150 (0.7%, 95% CI: 0.02–3.3%) stool samples. It seems that an etiological role of HCoVs is most likely in children with FS, considering that they had a higher proportion of positive HCoVs results than patients with AB and those with AGE, and had the highest viral load; however, the co-detection of other viruses was 52.6%. Trial Registration: ClinicalTrials.gov NCT00987519",2016 May 12,"['Jevšnik, Monika', 'Steyer, Andrej', 'Pokorn, Marko', 'Mrvič, Tatjana', 'Grosek, Štefan', 'Strle, Franc', 'Lusa, Lara', 'Petrovec, Miroslav']",PLoS One,,,True
abc8ce495c2a97f9b53e0b2b25a33adcf73de797,PMC,"The Role of Human Coronaviruses in Children Hospitalized for Acute Bronchiolitis, Acute Gastroenteritis, and Febrile Seizures: A 2-Year Prospective Study",http://dx.doi.org/10.1371/journal.pone.0155555,PMC4865086,27171141,CC BY,"Human coronaviruses (HCoVs) are associated with a variety of clinical presentations in children, but their role in disease remains uncertain. The objective of our prospective study was to investigate HCoVs associations with various clinical presentations in hospitalized children up to 6 years of age. Children hospitalized with acute bronchiolitis (AB), acute gastroenteritis (AGE), or febrile seizures (FS), and children admitted for elective surgical procedures (healthy controls) were included in the study. In patients with AB, AGE, and FS, a nasopharyngeal (NP) swab and blood sample were obtained upon admission and the follow-up visit 14 days later, whereas in children with AGE a stool sample was also acquired upon admission; in healthy controls a NP swab and stool sample were taken upon admission. Amplification of polymerase 1b gene was used to detect HCoVs in the specimens. HCoVs-positive specimens were also examined for the presence of several other viruses. HCoVs were most often detected in children with FS (19/192, 9.9%, 95% CI: 6–15%), followed by children with AGE (19/218, 8.7%, 95% CI: 5.3–13.3%) and AB (20/308, 6.5%, 95% CI: 4.0–9.8%). The presence of other viruses was a common finding, most frequent in the group of children with AB (19/20, 95%, 95% CI: 75.1–99.8%), followed by FS (10/19, 52.6%, 95% CI: 28.9–75.6%) and AGE (7/19, 36.8%, 95% CI: 16.3–61.6%). In healthy control children HCoVs were detected in 3/156 (1.9%, 95% CI: 0.4–5.5%) NP swabs and 1/150 (0.7%, 95% CI: 0.02–3.3%) stool samples. It seems that an etiological role of HCoVs is most likely in children with FS, considering that they had a higher proportion of positive HCoVs results than patients with AB and those with AGE, and had the highest viral load; however, the co-detection of other viruses was 52.6%. Trial Registration: ClinicalTrials.gov NCT00987519",2016 May 12,"['Jevšnik, Monika', 'Steyer, Andrej', 'Pokorn, Marko', 'Mrvič, Tatjana', 'Grosek, Štefan', 'Strle, Franc', 'Lusa, Lara', 'Petrovec, Miroslav']",PLoS One,,,False
d1fd684938b2d4358d1fde27a474bf71df02287b,PMC,Cytokine Profiles in Human Metapneumovirus Infected Children: Identification of Genes Involved in the Antiviral Response and Pathogenesis,http://dx.doi.org/10.1371/journal.pone.0155484,PMC4865088,27171557,CC BY,"Human metapneumovirus (hMPV) causes severe airway infection in children that may be caused by an unfavorable immune response. The nature of the innate immune response to hMPV in naturally occurring infections in children is largely undescribed, and it is unknown if inflammasome activation is implicated in disease pathogenesis. We examined nasopharynx aspirates and blood samples from hMPV-infected children without detectable co-infections. The expression of inflammatory and antiviral genes were measured in nasal airway secretions by relative mRNA quantification while blood plasma proteins were determined by a multiplex immunoassay. Several genes were significantly up-regulated at mRNA and protein level in the hMPV infected children. Most apparent was the expression of the chemokine IP-10, the pro-inflammatory cytokine IL-18 in addition to the interferon inducible gene ISG54. Interestingly, children experiencing more severe disease, as indicated by a severity index, had significantly more often up-regulation of the inflammasome-associated genes IL-1β and NLRP3. Overall, our data point to cytokines, particularly inflammasome-associated, that might be important in hMPV mediated lung disease and the antiviral response in children with severe infection. Our study is the first to demonstrate that inflammasome components are associated with increased illness severity in hMPV-infected children.",2016 May 12,"['Malmo, Jostein', 'Moe, Nina', 'Krokstad, Sidsel', 'Ryan, Liv', 'Loevenich, Simon', 'Johnsen, Ingvild B.', 'Espevik, Terje', 'Nordbø, Svein Arne', 'Døllner, Henrik', 'Anthonsen, Marit W.']",PLoS One,,,True
ffe663e4ef5018da41f057533520b9d85ec86e18,PMC,Global Variability in Reported Mortality for Critical Illness during the 2009-10 Influenza A(H1N1) Pandemic: A Systematic Review and Meta-Regression to Guide Reporting of Outcomes during Disease Outbreaks,http://dx.doi.org/10.1371/journal.pone.0155044,PMC4865181,27170999,CC BY,"PURPOSE: To determine how patient, healthcare system and study-specific factors influence reported mortality associated with critical illness during the 2009–2010 Influenza A (H1N1) pandemic. METHODS: Systematic review with meta-regression of studies reporting on mortality associated with critical illness during the 2009–2010 Influenza A (H1N1) pandemic. DATA SOURCES: Medline, Embase, LiLACs and African Index Medicus to June 2009-March 2016. RESULTS: 226 studies from 50 countries met our inclusion criteria. Mortality associated with H1N1-related critical illness was 31% (95% CI 28–34). Reported mortality was highest in South Asia (61% [95% CI 50–71]) and Sub-Saharan Africa (53% [95% CI 29–75]), in comparison to Western Europe (25% [95% CI 22–30]), North America (25% [95% CI 22–27]) and Australia (15% [95% CI 13–18]) (P<0.0001). High income economies had significantly lower reported mortality compared to upper middle income economies and lower middle income economies respectively (P<0.0001). Mortality for the first wave was non-significantly higher than wave two (P = 0.66). There was substantial variability in reported mortality among the specific subgroups of patients: unselected critically ill adults (27% [95% CI 24–30]), acute respiratory distress syndrome (37% [95% CI 32–44]), acute kidney injury (44% [95% CI 26–64]), and critically ill pregnant patients (10% [95% CI 5–19]). CONCLUSION: Reported mortality for outbreaks and pandemics may vary substantially depending upon selected patient characteristics, the number of patients described, and the region and economic status of the outbreak location. Outcomes from a relatively small number of patients from specific regions may lead to biased estimates of outcomes on a global scale.",2016 May 12,"['Duggal, Abhijit', 'Pinto, Ruxandra', 'Rubenfeld, Gordon', 'Fowler, Robert A.']",PLoS One,,,True
646d3092d14896e26c741391f0b5fe5b724f4a39,PMC,Rice endosperm is cost‐effective for the production of recombinant griffithsin with potent activity against HIV,http://dx.doi.org/10.1111/pbi.12507,PMC4865440,26800650,CC BY,"Protein microbicides containing neutralizing antibodies and antiviral lectins may help to reduce the rate of infection with human immunodeficiency virus (HIV) if it is possible to manufacture the components in large quantities at a cost affordable in HIV‐endemic regions such as sub‐Saharan Africa. We expressed the antiviral lectin griffithsin (GRFT), which shows potent neutralizing activity against HIV, in the endosperm of transgenic rice plants (Oryza sativa), to determine whether rice can be used to produce inexpensive GRFT as a microbicide ingredient. The yield of (OS)GRFT in the best‐performing plants was 223 μg/g dry seed weight. We also established a one‐step purification protocol, achieving a recovery of 74% and a purity of 80%, which potentially could be developed into a larger‐scale process to facilitate inexpensive downstream processing. (OS)GRFT bound to HIV glycans with similar efficiency to GRFT produced in Escherichia coli. Whole‐cell assays using purified (OS)GRFT and infectivity assays using crude extracts of transgenic rice endosperm confirmed that both crude and pure (OS)GRFT showed potent activity against HIV and the crude extracts were not toxic towards human cell lines, suggesting they could be administered as a microbicide with only minimal processing. A freedom‐to‐operate analysis confirmed that GRFT produced in rice is suitable for commercial development, and an economic evaluation suggested that 1.8 kg/ha of pure GRFT could be produced from rice seeds. Our data therefore indicate that rice could be developed as an inexpensive production platform for GRFT as a microbicide component.",2016 Jun 23,"['Vamvaka, Evangelia', 'Arcalis, Elsa', 'Ramessar, Koreen', 'Evans, Abbey', ""O'Keefe, Barry R."", 'Shattock, Robin J.', 'Medina, Vicente', 'Stöger, Eva', 'Christou, Paul', 'Capell, Teresa']",Plant Biotechnol J,,,True
a6176cded64c46ece2d4cef65ffdf638f4adceba,PMC,Strategies for Human Tumor Virus Discoveries: From Microscopic Observation to Digital Transcriptome Subtraction,http://dx.doi.org/10.3389/fmicb.2016.00676,PMC4865503,27242703,CC BY,"Over 20% of human cancers worldwide are associated with infectious agents, including viruses, bacteria, and parasites. Various methods have been used to identify human tumor viruses, including electron microscopic observations of viral particles, immunologic screening, cDNA library screening, nucleic acid hybridization, consensus PCR, viral DNA array chip, and representational difference analysis. With the Human Genome Project, a large amount of genetic information from humans and other organisms has accumulated over the last decade. Utilizing the available genetic databases, Feng et al. (2007) developed digital transcriptome subtraction (DTS), an in silico method to sequentially subtract human sequences from tissue or cellular transcriptome, and discovered Merkel cell polyomavirus (MCV) from Merkel cell carcinoma. Here, we review the background and methods underlying the human tumor virus discoveries and explain how DTS was developed and used for the discovery of MCV.",2016 May 13,"['Mirvish, Ezra D.', 'Shuda, Masahiro']",Front Microbiol,,,True
222534164391422210b3089109605e8ff4d1d46c,PMC,SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-β1 via ROS/p38 MAPK/STAT3 pathway,http://dx.doi.org/10.1038/srep25754,PMC4865725,27173006,CC BY,"SARS coronavirus (SARS-CoV) papain-like protease (PLpro) has been identified in TGF-β1 up-regulation in human promonocytes (Proteomics 2012, 12: 3193-205). This study investigates the mechanisms of SARS-CoV PLpro-induced TGF-β1 promoter activation in human lung epithelial cells and mouse models. SARS-CoV PLpro dose- and time-dependently up-regulates TGF-β1 and vimentin in A549 cells. Dual luciferase reporter assays with TGF-β1 promoter plasmids indicated that TGF-β1 promoter region between −175 to −60, the Egr-1 binding site, was responsible for TGF-β1 promoter activation induced by SARS-CoV PLpro. Subcellular localization analysis of transcription factors showed PLpro triggering nuclear translocation of Egr-1, but not NF-κB and Sp-1. Meanwhile, Egr-1 silencing by siRNA significantly reduced PLpro-induced up-regulation of TGF-β1, TSP-1 and pro-fibrotic genes. Furthermore, the inhibitors for ROS (YCG063), p38 MAPK (SB203580), and STAT3 (Stattic) revealed ROS/p38 MAPK/STAT3 pathway involving in Egr-1 dependent activation of TGF-β1 promoter induced by PLpro. In a mouse model with a direct pulmonary injection, PLpro stimulated macrophage infiltration into lung, up-regulating Egr-1, TSP-1, TGF-β1 and vimentin expression in lung tissues. The results revealed that SARS-CoV PLpro significantly triggered Egr-1 dependent activation of TGF-β1 promoter via ROS/p38 MAPK/STAT3 pathway, correlating with up-regulation of pro-fibrotic responses in vitro and in vivo.",2016 May 13,"['Li, Shih-Wein', 'Wang, Ching-Ying', 'Jou, Yu-Jen', 'Yang, Tsuey-Ching', 'Huang, Su-Hua', 'Wan, Lei', 'Lin, Ying-Ju', 'Lin, Cheng-Wen']",Sci Rep,,,True
479b22be77d8770d98513f73d21841020e7a9cbe,PMC,SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-β1 via ROS/p38 MAPK/STAT3 pathway,http://dx.doi.org/10.1038/srep25754,PMC4865725,27173006,CC BY,"SARS coronavirus (SARS-CoV) papain-like protease (PLpro) has been identified in TGF-β1 up-regulation in human promonocytes (Proteomics 2012, 12: 3193-205). This study investigates the mechanisms of SARS-CoV PLpro-induced TGF-β1 promoter activation in human lung epithelial cells and mouse models. SARS-CoV PLpro dose- and time-dependently up-regulates TGF-β1 and vimentin in A549 cells. Dual luciferase reporter assays with TGF-β1 promoter plasmids indicated that TGF-β1 promoter region between −175 to −60, the Egr-1 binding site, was responsible for TGF-β1 promoter activation induced by SARS-CoV PLpro. Subcellular localization analysis of transcription factors showed PLpro triggering nuclear translocation of Egr-1, but not NF-κB and Sp-1. Meanwhile, Egr-1 silencing by siRNA significantly reduced PLpro-induced up-regulation of TGF-β1, TSP-1 and pro-fibrotic genes. Furthermore, the inhibitors for ROS (YCG063), p38 MAPK (SB203580), and STAT3 (Stattic) revealed ROS/p38 MAPK/STAT3 pathway involving in Egr-1 dependent activation of TGF-β1 promoter induced by PLpro. In a mouse model with a direct pulmonary injection, PLpro stimulated macrophage infiltration into lung, up-regulating Egr-1, TSP-1, TGF-β1 and vimentin expression in lung tissues. The results revealed that SARS-CoV PLpro significantly triggered Egr-1 dependent activation of TGF-β1 promoter via ROS/p38 MAPK/STAT3 pathway, correlating with up-regulation of pro-fibrotic responses in vitro and in vivo.",2016 May 13,"['Li, Shih-Wein', 'Wang, Ching-Ying', 'Jou, Yu-Jen', 'Yang, Tsuey-Ching', 'Huang, Su-Hua', 'Wan, Lei', 'Lin, Ying-Ju', 'Lin, Cheng-Wen']",Sci Rep,,,False
afac5482c4fb73ba67db7127e3d0c9ed19882c35,PMC,An RNA-dependent RNA polymerase gene in bat genomes derived from an ancient negative-strand RNA virus,http://dx.doi.org/10.1038/srep25873,PMC4865735,27174689,CC BY,"Endogenous bornavirus-like L (EBLL) elements are inheritable sequences derived from ancient bornavirus L genes that encode a viral RNA-dependent RNA polymerase (RdRp) in many eukaryotic genomes. Here, we demonstrate that bats of the genus Eptesicus have preserved for more than 11.8 million years an EBLL element named eEBLL-1, which has an intact open reading frame of 1,718 codons. The eEBLL-1 coding sequence revealed that functional motifs essential for mononegaviral RdRp activity are well conserved in the EBLL-1 genes. Genetic analyses showed that natural selection operated on eEBLL-1 during the evolution of Eptesicus. Notably, we detected efficient transcription of eEBLL-1 in tissues from Eptesicus bats. To the best of our knowledge, this study is the first report showing that the eukaryotic genome has gained a riboviral polymerase gene from an ancient virus that has the potential to encode a functional RdRp.",2016 May 13,"['Horie, Masayuki', 'Kobayashi, Yuki', 'Honda, Tomoyuki', 'Fujino, Kan', 'Akasaka, Takumi', 'Kohl, Claudia', 'Wibbelt, Gudrun', 'Mühldorfer, Kristin', 'Kurth, Andreas', 'Müller, Marcel A.', 'Corman, Victor M.', 'Gillich, Nadine', 'Suzuki, Yoshiyuki', 'Schwemmle, Martin', 'Tomonaga, Keizo']",Sci Rep,,,True
4d17dcfe7d1c0280f69bc876f1c6049e79e5bca0,PMC,An RNA-dependent RNA polymerase gene in bat genomes derived from an ancient negative-strand RNA virus,http://dx.doi.org/10.1038/srep25873,PMC4865735,27174689,CC BY,"Endogenous bornavirus-like L (EBLL) elements are inheritable sequences derived from ancient bornavirus L genes that encode a viral RNA-dependent RNA polymerase (RdRp) in many eukaryotic genomes. Here, we demonstrate that bats of the genus Eptesicus have preserved for more than 11.8 million years an EBLL element named eEBLL-1, which has an intact open reading frame of 1,718 codons. The eEBLL-1 coding sequence revealed that functional motifs essential for mononegaviral RdRp activity are well conserved in the EBLL-1 genes. Genetic analyses showed that natural selection operated on eEBLL-1 during the evolution of Eptesicus. Notably, we detected efficient transcription of eEBLL-1 in tissues from Eptesicus bats. To the best of our knowledge, this study is the first report showing that the eukaryotic genome has gained a riboviral polymerase gene from an ancient virus that has the potential to encode a functional RdRp.",2016 May 13,"['Horie, Masayuki', 'Kobayashi, Yuki', 'Honda, Tomoyuki', 'Fujino, Kan', 'Akasaka, Takumi', 'Kohl, Claudia', 'Wibbelt, Gudrun', 'Mühldorfer, Kristin', 'Kurth, Andreas', 'Müller, Marcel A.', 'Corman, Victor M.', 'Gillich, Nadine', 'Suzuki, Yoshiyuki', 'Schwemmle, Martin', 'Tomonaga, Keizo']",Sci Rep,,,False
9671b5d479956e73b3f749873f672dd421019b80,PMC,An RNA-dependent RNA polymerase gene in bat genomes derived from an ancient negative-strand RNA virus,http://dx.doi.org/10.1038/srep25873,PMC4865735,27174689,CC BY,"Endogenous bornavirus-like L (EBLL) elements are inheritable sequences derived from ancient bornavirus L genes that encode a viral RNA-dependent RNA polymerase (RdRp) in many eukaryotic genomes. Here, we demonstrate that bats of the genus Eptesicus have preserved for more than 11.8 million years an EBLL element named eEBLL-1, which has an intact open reading frame of 1,718 codons. The eEBLL-1 coding sequence revealed that functional motifs essential for mononegaviral RdRp activity are well conserved in the EBLL-1 genes. Genetic analyses showed that natural selection operated on eEBLL-1 during the evolution of Eptesicus. Notably, we detected efficient transcription of eEBLL-1 in tissues from Eptesicus bats. To the best of our knowledge, this study is the first report showing that the eukaryotic genome has gained a riboviral polymerase gene from an ancient virus that has the potential to encode a functional RdRp.",2016 May 13,"['Horie, Masayuki', 'Kobayashi, Yuki', 'Honda, Tomoyuki', 'Fujino, Kan', 'Akasaka, Takumi', 'Kohl, Claudia', 'Wibbelt, Gudrun', 'Mühldorfer, Kristin', 'Kurth, Andreas', 'Müller, Marcel A.', 'Corman, Victor M.', 'Gillich, Nadine', 'Suzuki, Yoshiyuki', 'Schwemmle, Martin', 'Tomonaga, Keizo']",Sci Rep,,,False
413383034f00fe7c2c81688ac152dc102963d08b,PMC,Targeted next-generation sequencing for the detection of ciprofloxacin resistance markers using molecular inversion probes,http://dx.doi.org/10.1038/srep25904,PMC4865750,27174456,CC BY,"Antibiotic resistance (AR) is an epidemic of increasing magnitude requiring rapid identification and profiling for appropriate and timely therapeutic measures and containment strategies. In this context, ciprofloxacin is part of the first-line of countermeasures against numerous high consequence bacteria. Significant resistance can occur via single nucleotide polymorphisms (SNP) and deletions within ciprofloxacin targeted genes. Ideally, use of ciprofloxacin would be prefaced with AR determination to avoid overuse or misuse of the antibiotic. Here, we describe the development and evaluation of a panel of 44 single-stranded molecular inversion probes (MIPs) coupled to next-generation sequencing (NGS) for the detection of genetic variants known to confer ciprofloxacin resistance in Bacillus anthracis, Yersinia pestis, and Francisella tularensis. Sequencing results demonstrate MIPs capture and amplify targeted regions of interest at significant levels of coverage. Depending on the genetic variant, limits of detection (LOD) for high-throughput pooled sequencing ranged from approximately 300–1800 input genome copies. LODs increased 10-fold in the presence of contaminating human genome DNA. In addition, we show that MIPs can be used as an enrichment step with high resolution melt (HRM) real-time PCR which is a sensitive assay with a rapid time-to-answer. Overall, this technology is a multiplexable upfront enrichment applicable with multiple downstream molecular assays for the detection of targeted genetic regions.",2016 May 13,"['Stefan, Christopher P.', 'Koehler, Jeffrey W.', 'Minogue, Timothy D.']",Sci Rep,,,True
61bf04a5d7173cec5cbd4fbb977deeaf09e2c678,PMC,Targeted next-generation sequencing for the detection of ciprofloxacin resistance markers using molecular inversion probes,http://dx.doi.org/10.1038/srep25904,PMC4865750,27174456,CC BY,"Antibiotic resistance (AR) is an epidemic of increasing magnitude requiring rapid identification and profiling for appropriate and timely therapeutic measures and containment strategies. In this context, ciprofloxacin is part of the first-line of countermeasures against numerous high consequence bacteria. Significant resistance can occur via single nucleotide polymorphisms (SNP) and deletions within ciprofloxacin targeted genes. Ideally, use of ciprofloxacin would be prefaced with AR determination to avoid overuse or misuse of the antibiotic. Here, we describe the development and evaluation of a panel of 44 single-stranded molecular inversion probes (MIPs) coupled to next-generation sequencing (NGS) for the detection of genetic variants known to confer ciprofloxacin resistance in Bacillus anthracis, Yersinia pestis, and Francisella tularensis. Sequencing results demonstrate MIPs capture and amplify targeted regions of interest at significant levels of coverage. Depending on the genetic variant, limits of detection (LOD) for high-throughput pooled sequencing ranged from approximately 300–1800 input genome copies. LODs increased 10-fold in the presence of contaminating human genome DNA. In addition, we show that MIPs can be used as an enrichment step with high resolution melt (HRM) real-time PCR which is a sensitive assay with a rapid time-to-answer. Overall, this technology is a multiplexable upfront enrichment applicable with multiple downstream molecular assays for the detection of targeted genetic regions.",2016 May 13,"['Stefan, Christopher P.', 'Koehler, Jeffrey W.', 'Minogue, Timothy D.']",Sci Rep,,,False
7d5cd4faf19ae8838653aa65ea172c97f8bfe9f4,PMC,X-Ray Structure and Inhibition of 3C-like Protease from Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.1038/srep25961,PMC4865815,27173881,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a coronavirus that infects pigs and can have mortality rates approaching 100% in piglets, causing serious economic impact. The 3C-like protease (3CL(pro)) is essential for the coronaviral life cycle and is an appealing target for the development of therapeutics. We report the expression, purification, crystallization and 2.10 Å X-ray structure of 3CL(pro) from PEDV. Analysis of the PEDV 3CL(pro) structure and comparison to other coronaviral 3CL(pro)’s from the same alpha-coronavirus phylogeny shows that the overall structures and active site architectures across 3CL(pro)’s are conserved, with the exception of a loop that comprises the protease S(2) pocket. We found a known inhibitor of severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL(pro), (R)-16, to have inhibitor activity against PEDV 3CL(pro), despite that SARS-3CL(pro) and PEDV 3CL(pro) share only 45.4% sequence identity. Structural comparison reveals that the majority of residues involved in (R)-16 binding to SARS-3CL(pro) are conserved in PEDV-3CL(pro); however, the sequence variation and positional difference in the loop forming the S(2) pocket may account for large observed difference in IC(50) values. This work advances our understanding of the subtle, but important, differences in coronaviral 3CL(pro) architecture and contributes to the broader structural knowledge of coronaviral 3CL(pro)’s.",2016 May 13,"['St. John, Sarah E.', 'Anson, Brandon J.', 'Mesecar, Andrew D.']",Sci Rep,,,True
bf114390000199ac4f7c1f1f07c3320f0cb38657,PMC,Potent neutralizing monoclonal antibodies against Ebola virus infection,http://dx.doi.org/10.1038/srep25856,PMC4867612,27181584,CC BY,"Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection.",2016 May 16,"['Zhang, Qi', 'Gui, Miao', 'Niu, Xuefeng', 'He, Shihua', 'Wang, Ruoke', 'Feng, Yupeng', 'Kroeker, Andrea', 'Zuo, Yanan', 'Wang, Hua', 'Wang, Ying', 'Li, Jiade', 'Li, Chufang', 'Shi, Yi', 'Shi, Xuanling', 'Gao, George F.', 'Xiang, Ye', 'Qiu, Xiangguo', 'Chen, Ling', 'Zhang, Linqi']",Sci Rep,,,True
db141d655abc3f86c6754e91cf00b56307124194,PMC,Potent neutralizing monoclonal antibodies against Ebola virus infection,http://dx.doi.org/10.1038/srep25856,PMC4867612,27181584,CC BY,"Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection.",2016 May 16,"['Zhang, Qi', 'Gui, Miao', 'Niu, Xuefeng', 'He, Shihua', 'Wang, Ruoke', 'Feng, Yupeng', 'Kroeker, Andrea', 'Zuo, Yanan', 'Wang, Hua', 'Wang, Ying', 'Li, Jiade', 'Li, Chufang', 'Shi, Yi', 'Shi, Xuanling', 'Gao, George F.', 'Xiang, Ye', 'Qiu, Xiangguo', 'Chen, Ling', 'Zhang, Linqi']",Sci Rep,,,False
6039b17b00ec8948aa66da30a1164ed9634e3ceb,PMC,Surveillance and response systems for elimination of tropical diseases: summary of a thematic series in Infectious Diseases of Poverty,http://dx.doi.org/10.1186/s40249-016-0144-7,PMC4868018,27179509,CC BY,"The peer-reviewed journal Infectious Diseases of Poverty provides a new platform to engage with, and disseminate in an open-access format, science outside traditional disciplinary boundaries. The current piece reviews a thematic series on surveillance-response systems for elimination of tropical diseases. Overall, 22 contributions covering a broad array of diseases are featured – i.e. clonorchiasis, dengue, hepatitis, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), H7N9 avian influenza, lymphatic filariasis, malaria, Middle East respiratory syndrome (MERS), rabies, schistosomiasis and tuberculosis (TB). There are five scoping reviews, a commentary, a letter to the editor, an opinion piece and an editorial pertaining to the theme “Elimination of tropical disease through surveillance and response”. The remaining 13 articles are original contributions mainly covering (i) drug resistance; (ii) innovation and validation in the field of mathematical modelling; (iii) elimination of infectious diseases; and (iv) social media reports on disease outbreak notifications released by national health authorities. Analysis of the authors’ affiliations reveals that scientists from the People’s Republic of China (P.R. China) are prominently represented. Possible explanations include the fact that the 2012 and 2014 international conferences pertaining to surveillance-response mechanisms were both hosted by the National Institute of Parasitic Diseases (NIPD) in Shanghai, coupled with P.R. China’s growing importance with regard to the control of infectious diseases. Within 4 to 22 months of publication, three of the 22 contributions were viewed more than 10 000 times each. With sustained efforts focusing on relevant and strategic information towards control and elimination of infectious diseases, Infectious Diseases of Poverty has become a leading journal in the field of surveillance and response systems in infectious diseases and beyond. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0144-7) contains supplementary material, which is available to authorized users.",2016 May 14,"['Zhou, Xia', 'Yap, Peiling', 'Tanner, Marcel', 'Bergquist, Robert', 'Utzinger, Jürg', 'Zhou, Xiao-Nong']",Infect Dis Poverty,,,False
17787dbfbb012b537726971936c74cab0aa701b1,PMC,Surveillance and response systems for elimination of tropical diseases: summary of a thematic series in Infectious Diseases of Poverty,http://dx.doi.org/10.1186/s40249-016-0144-7,PMC4868018,27179509,CC BY,"The peer-reviewed journal Infectious Diseases of Poverty provides a new platform to engage with, and disseminate in an open-access format, science outside traditional disciplinary boundaries. The current piece reviews a thematic series on surveillance-response systems for elimination of tropical diseases. Overall, 22 contributions covering a broad array of diseases are featured – i.e. clonorchiasis, dengue, hepatitis, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), H7N9 avian influenza, lymphatic filariasis, malaria, Middle East respiratory syndrome (MERS), rabies, schistosomiasis and tuberculosis (TB). There are five scoping reviews, a commentary, a letter to the editor, an opinion piece and an editorial pertaining to the theme “Elimination of tropical disease through surveillance and response”. The remaining 13 articles are original contributions mainly covering (i) drug resistance; (ii) innovation and validation in the field of mathematical modelling; (iii) elimination of infectious diseases; and (iv) social media reports on disease outbreak notifications released by national health authorities. Analysis of the authors’ affiliations reveals that scientists from the People’s Republic of China (P.R. China) are prominently represented. Possible explanations include the fact that the 2012 and 2014 international conferences pertaining to surveillance-response mechanisms were both hosted by the National Institute of Parasitic Diseases (NIPD) in Shanghai, coupled with P.R. China’s growing importance with regard to the control of infectious diseases. Within 4 to 22 months of publication, three of the 22 contributions were viewed more than 10 000 times each. With sustained efforts focusing on relevant and strategic information towards control and elimination of infectious diseases, Infectious Diseases of Poverty has become a leading journal in the field of surveillance and response systems in infectious diseases and beyond. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0144-7) contains supplementary material, which is available to authorized users.",2016 May 14,"['Zhou, Xia', 'Yap, Peiling', 'Tanner, Marcel', 'Bergquist, Robert', 'Utzinger, Jürg', 'Zhou, Xiao-Nong']",Infect Dis Poverty,,,True
962b1eed7da37d26000eb9232c49851420b1e662,PMC,Feline Coronavirus 3c Protein: A Candidate for a Virulence Marker?,http://dx.doi.org/10.1155/2016/8560691,PMC4868892,27243037,CC BY,"Feline infectious peritonitis virus (FIPV) is highly virulent and responsible for the highly fatal disease feline infectious peritonitis (FIP), whereas feline enteric coronavirus (FECV) is widespread among the feline population and typically causes asymptomatic infections. Some candidates for genetic markers capable of differentiating these two pathotypes of a unique virus (feline coronavirus) have been proposed by several studies. In the present survey, in order to search for markers that can differentiate FECV and FIPV, several clones of the 3a–c, E, and M genes were sequenced from samples obtained from cats with or without FIP. All genes showed genetic diversity and suggested the presence of FCoV mutant spectrum capable of producing a virulent pathotype in an individual-specific way. In addition, all the feline coronavirus FIPV strains demonstrated a truncated 3c protein, and the 3c gene was the only observed pathotypic marker for FCoVs, showing that 3c gene is a candidate marker for the distinction between the two pathotypes when the mutant spectrum is taken into account.",2016 May 3,"['Hora, A. S.', 'Tonietti, P. O.', 'Taniwaki, S. A.', 'Asano, K. M.', 'Maiorka, P.', 'Richtzenhain, L. J.', 'Brandão, P. E.']",Biomed Res Int,,,True
67d137d0496d7339e302c18d693c7ec960ddf733,PMC,Moving towards a new vision: implementation of a public health policy intervention,http://dx.doi.org/10.1186/s12889-016-3056-3,PMC4869271,27185039,CC BY,"BACKGROUND: Public health systems in Canada have undergone significant policy renewal over the last decade in response to threats to the public’s health, such as severe acute respiratory syndrome. There is limited research on how public health policies have been implemented or what has influenced their implementation. This paper explores policy implementation in two exemplar public health programs -chronic disease prevention and sexually-transmitted infection prevention - in Ontario, Canada. It examines public health service providers’, managers’ and senior managements’ perspectives on the process of implementation of the Ontario Public Health Standards 2008 and factors influencing implementation. METHODS: Public health staff from six health units representing rural, remote, large and small urban settings were included. We conducted 21 focus groups and 18 interviews between 2010 (manager and staff focus groups) and 2011 (senior management interviews) involving 133 participants. Research assistants coded transcripts and researchers reviewed these; the research team discussed and resolved discrepancies. To facilitate a breadth of perspectives, several team members helped interpret the findings. An integrated knowledge translation approach was used, reflected by the inclusion of academics as well as decision-makers on the team and as co-authors. RESULTS: Front line service providers often were unaware of the new policies but managers and senior management incorporated them in operational and program planning. Some participants were involved in policy development or provided feedback prior to their launch. Implementation was influenced by many factors that aligned with Greenhalgh and colleagues’ empirically-based Diffusion of Innovations in Service Organizations Framework. Factors and related components that were most clearly linked to the OPHS policy implementation were: attributes of the innovation itself; adoption by individuals; diffusion and dissemination;the outer context – interorganizational networks and collaboration; the inner setting – implementation processes and routinization; and, linkage at the design and implementation stage. CONCLUSIONS: Multiple factors influenced public health policy implementation. Results provide empirical support for components of Greenhalgh et al’s framework and suggest two additional components – the role of external organizational collaborations and partnerships as well as planning processes in influencing implementation. These are important to consider by government and public health organizations when promoting new or revised public health policies as they evolve over time. A successful policy implementation process in Ontario has helped to move public health towards the new vision. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-3056-3) contains supplementary material, which is available to authorized users.",2016 May 17,"['Valaitis, Ruta', 'MacDonald, Marjorie', 'Kothari, Anita', 'O’Mara, Linda', 'Regan, Sandra', 'Garcia, John', 'Murray, Nancy', 'Manson, Heather', 'Peroff-Johnston, Nancy', 'Bursey, Gayle', 'Boyko, Jennifer']",BMC Public Health,,,True
f046ba37a3a60a90b3dbcc977182efe1672ba300,PMC,Viruses are a dominant driver of protein adaptation in mammals,http://dx.doi.org/10.7554/eLife.12469,PMC4869911,27187613,CC BY,"Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is unknown. Here, we analyze adaptation in ~1300 virus-interacting proteins manually curated from a set of 9900 proteins conserved in all sequenced mammalian genomes. We show that viruses (i) use the more evolutionarily constrained proteins within the cellular functions they interact with and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. We conservatively estimate that viruses have driven close to 30% of all adaptive amino acid changes in the part of the human proteome conserved within mammals. Our results suggest that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes. DOI: http://dx.doi.org/10.7554/eLife.12469.001",,"['Enard, David', 'Cai, Le', 'Gwennap, Carina', 'Petrov, Dmitri A']",eLife.; 5:e12469,,,True
9a89705854ab91a21b721dd3900a91d6332c1eaf,PMC,Imaging Axonal Degeneration and Repair in Preclinical Animal Models of Multiple Sclerosis,http://dx.doi.org/10.3389/fimmu.2016.00189,PMC4871863,27242796,CC BY,"Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by chronic neuroinflammation, demyelination, and axonal damage. Infiltration of activated lymphocytes and myeloid cells are thought to be primarily responsible for white matter damage and axonopathy. Over time, this neurologic damage manifests clinically as debilitating motor and cognitive symptoms. Existing MS therapies focus on symptom relief and delay of disease progression through reduction of neuroinflammation. However, long-term strategies to remyelinate, protect, or regenerate axons have remained elusive, posing a challenge to treating progressive forms of MS. Preclinical mouse models and techniques, such as immunohistochemistry, flow cytometry, and genomic and proteomic analysis have provided advances in our understanding of discrete time-points of pathology following disease induction. More recently, in vivo and in situ two-photon (2P) microscopy has made it possible to visualize continuous real-time cellular behavior and structural changes occurring within the CNS during neuropathology. Research utilizing 2P imaging to study axonopathy in neuroinflammatory demyelinating disease has focused on five areas: (1) axonal morphologic changes, (2) organelle transport and health, (3) relationship to inflammation, (4) neuronal excitotoxicity, and (5) regenerative therapies. 2P imaging may also be used to identify novel therapeutic targets via identification and clarification of dynamic cellular and molecular mechanisms of axonal regeneration and remyelination. Here, we review tools that have made 2P accessible for imaging neuropathologies and advances in our understanding of axonal degeneration and repair in preclinical models of demyelinating diseases.",2016 May 19,"['Yandamuri, Soumya S.', 'Lane, Thomas E.']",Front Immunol,,,True
87b2f2205b9dea38eeaeddd6e3ddbb6e45f542ae,PMC,Genome-Wide Transcriptional Profiling Reveals Two Distinct Outcomes in Central Nervous System Infections of Rabies Virus,http://dx.doi.org/10.3389/fmicb.2016.00751,PMC4871871,27242764,CC BY,"Rabies remains a major public health concern in many developing countries. The precise neuropathogenesis of rabies is unknown, though it is hypothesized to be due to neuronal death or dysfunction. Mice that received intranasal inoculation of an attenuated rabies virus (RABV) strain HEP-Flury exhibited subtle clinical signs, and eventually recovered, which is different from the fatal encephalitis caused by the virulent RABV strain CVS-11. To understand the neuropathogenesis of rabies and the mechanisms of viral clearance, we applied RNA sequencing (RNA-Seq) to compare the brain transcriptomes of normal mice vs. HEP-Flury or CVS-11 intranasally inoculated mice. Our results revealed that both RABV strains altered positively and negatively the expression levels of many host genes, including genes associated with innate and adaptive immunity, inflammation and cell death. It is found that HEP-Flury infection can activate the innate immunity earlier through the RIG-I/MDA-5 signaling, and the innate immunity pre-activated by HEP-Flury or Newcastle disease virus (NDV) infection can effectively prevent the CVS-11 to invade central nervous system (CNS), but fails to clear the CVS-11 after its entry into the CNS. In addition, following CVS-11 infection, genes implicated in cell adhesion, blood vessel morphogenesis and coagulation were mainly up-regulated, while the genes involved in synaptic transmission and ion transport were significantly down-regulated. On the other hand, several genes involved in the MHC class II-mediated antigen presentation pathway were activated to a greater extent after the HEP-Flury infection as compared with the CVS-11 infection suggesting that the collaboration of CD4(+) T cells and MHC class II-mediated antigen presentation is critical for the clearance of attenuated RABV from the CNS. The differentially regulated genes reported here are likely to include potential therapeutic targets for expanding the post-exposure treatment window for RABV infection.",2016 May 19,"['Zhang, Daiting', 'He, Feilong', 'Bi, Shuilian', 'Guo, Huixia', 'Zhang, Baoshi', 'Wu, Fan', 'Liang, Jiaqi', 'Yang, Youtian', 'Tian, Qin', 'Ju, Chunmei', 'Fan, Huiying', 'Chen, Jinding', 'Guo, Xiaofeng', 'Luo, Yongwen']",Front Microbiol,,,True
24f49539fad81e8f8b10650eb9cbfd60c8ee23f5,PMC,Functional analysis of the N-terminal basic motif of a eukaryotic satellite RNA virus capsid protein in replication and packaging,http://dx.doi.org/10.1038/srep26328,PMC4872054,27193742,CC BY,"Efficient replication and assembly of virus particles are integral to the establishment of infection. In addition to the primary role of the capsid protein (CP) in encapsidating the RNA progeny, experimental evidence on positive sense single-stranded RNA viruses suggests that the CP also regulates RNA synthesis. Here, we demonstrate that replication of Satellite tobacco mosaic virus (STMV) is controlled by the cooperative interaction between STMV CP and the helper virus (HV) Tobacco mosaic virus (TMV) replicase. We identified that the STMV CP-HV replicase interaction requires a positively charged residue at the third position (3R) in the N-terminal 13 amino acid (aa) motif. Far-Northwestern blotting showed that STMV CP promotes binding between HV-replicase and STMV RNA. An STMV CP variant having an arginine to alanine substitution at position 3 in the N-terminal 13aa motif abolished replicase-CP binding. The N-terminal 13aa motif of the CP bearing alanine substitutions for positively charged residues located at positions 5, 7, 10 and 11 are defective in packaging full-length STMV, but can package a truncated STMV RNA lacking the 3′ terminal 150 nt region. These findings provide insights into the mechanism underlying the regulation of STMV replication and packaging.",2016 May 19,"['Sivanandam, Venkatesh', 'Mathews, Deborah', 'Garmann, Rees', 'Erdemci-Tandogan, Gonca', 'Zandi, Roya', 'Rao, A. L. N.']",Sci Rep,,,True
1b8a085682d10dad4baf90417a8cbcde144cc8c9,PMC,Disease management with ARIMA model in time series,http://dx.doi.org/10.1590/S1679-45082013000100024,PMC4872983,23579758,CC BY,"The evaluation of infectious and noninfectious disease management can be done through the use of a time series analysis. In this study, we expect to measure the results and prevent intervention effects on the disease. Clinical studies have benefited from the use of these techniques, particularly for the wide applicability of the ARIMA model. This study briefly presents the process of using the ARIMA model. This analytical tool offers a great contribution for researchers and healthcare managers in the evaluation of healthcare interventions in specific populations.",2013 Jan-Mar,"Sato, Renato Cesar",Einstein (Sao Paulo),,,True
859410b0052a50da3868ab631c6e1a58ff3d4c49,PMC,Toward a Common Secure Future: Four Global Commissions in the Wake of Ebola,http://dx.doi.org/10.1371/journal.pmed.1002042,PMC4873000,27195954,CC BY,Lawrence Gostin and colleagues offer a set of priorities for global health preparedness and response for future infectious disease threats.,2016 May 19,"['Gostin, Lawrence O.', 'Tomori, Oyewale', 'Wibulpolprasert, Suwit', 'Jha, Ashish K.', 'Frenk, Julio', 'Moon, Suerie', 'Phumaphi, Joy', 'Piot, Peter', 'Stocking, Barbara', 'Dzau, Victor J.', 'Leung, Gabriel M.']",PLoS Med,,,True
0a851d4005336287cd41901a8fcd0ba3bab686c9,PMC,Coinfections of the Respiratory Tract: Viral Competition for Resources,http://dx.doi.org/10.1371/journal.pone.0155589,PMC4873262,27196110,CC BY,"Studies have shown that simultaneous infection of the respiratory tract with at least two viruses is common in hospitalized patients, although it is not clear whether these infections are more or less severe than single virus infections. We use a mathematical model to study the dynamics of viral coinfection of the respiratory tract in an effort to understand the kinetics of these infections. Specifically, we use our model to investigate coinfections of influenza, respiratory syncytial virus, rhinovirus, parainfluenza virus, and human metapneumovirus. Our study shows that during coinfections, one virus can block another simply by being the first to infect the available host cells; there is no need for viral interference through immune response interactions. We use the model to calculate the duration of detectable coinfection and examine how it varies as initial viral dose and time of infection are varied. We find that rhinovirus, the fastest-growing virus, reduces replication of the remaining viruses during a coinfection, while parainfluenza virus, the slowest-growing virus is suppressed in the presence of other viruses.",2016 May 19,"['Pinky, Lubna', 'Dobrovolny, Hana M.']",PLoS One,,,True
d56e6ff1dc73a424b1ea4f7f97f1cac72eb67b39,PMC,Coinfections of the Respiratory Tract: Viral Competition for Resources,http://dx.doi.org/10.1371/journal.pone.0155589,PMC4873262,27196110,CC BY,"Studies have shown that simultaneous infection of the respiratory tract with at least two viruses is common in hospitalized patients, although it is not clear whether these infections are more or less severe than single virus infections. We use a mathematical model to study the dynamics of viral coinfection of the respiratory tract in an effort to understand the kinetics of these infections. Specifically, we use our model to investigate coinfections of influenza, respiratory syncytial virus, rhinovirus, parainfluenza virus, and human metapneumovirus. Our study shows that during coinfections, one virus can block another simply by being the first to infect the available host cells; there is no need for viral interference through immune response interactions. We use the model to calculate the duration of detectable coinfection and examine how it varies as initial viral dose and time of infection are varied. We find that rhinovirus, the fastest-growing virus, reduces replication of the remaining viruses during a coinfection, while parainfluenza virus, the slowest-growing virus is suppressed in the presence of other viruses.",2016 May 19,"['Pinky, Lubna', 'Dobrovolny, Hana M.']",PLoS One,,,False
c6f5f979821e78c2d91b1f93a162f3c8542fb64f,PMC,Coinfections of the Respiratory Tract: Viral Competition for Resources,http://dx.doi.org/10.1371/journal.pone.0155589,PMC4873262,27196110,CC BY,"Studies have shown that simultaneous infection of the respiratory tract with at least two viruses is common in hospitalized patients, although it is not clear whether these infections are more or less severe than single virus infections. We use a mathematical model to study the dynamics of viral coinfection of the respiratory tract in an effort to understand the kinetics of these infections. Specifically, we use our model to investigate coinfections of influenza, respiratory syncytial virus, rhinovirus, parainfluenza virus, and human metapneumovirus. Our study shows that during coinfections, one virus can block another simply by being the first to infect the available host cells; there is no need for viral interference through immune response interactions. We use the model to calculate the duration of detectable coinfection and examine how it varies as initial viral dose and time of infection are varied. We find that rhinovirus, the fastest-growing virus, reduces replication of the remaining viruses during a coinfection, while parainfluenza virus, the slowest-growing virus is suppressed in the presence of other viruses.",2016 May 19,"['Pinky, Lubna', 'Dobrovolny, Hana M.']",PLoS One,,,False
40b1e8bb31863fa9488fcbfc590edf4972fe4c0c,PMC,"Glial cell activation, recruitment, and survival of B-lineage cells following MCMV brain infection",http://dx.doi.org/10.1186/s12974-016-0582-y,PMC4874004,27207308,CC BY,"BACKGROUND: Chemokines produced by reactive glia drive migration of immune cells and previous studies from our laboratory have demonstrated that CD19(+) B cells infiltrate the brain. In this study, in vivo and in vitro experiments investigated the role of reactive glial cells in recruitment and survival of B-lineage cells in response to (murine cytomegalovirus) MCMV infection. METHODS: Flow cytometric analysis was used to assess chemokine receptor expression on brain-infiltrating B cells. Real-time RT-PCR and ELISA were used to measure chemokine levels. Dual-immunohistochemical staining was used to co-localize chemokine production by reactive glia. Primary glial cell cultures and migration assays were used to examine chemokine-mediated recruitment. Astrocyte: B cell co-cultures were used to investigate survival and proliferation. RESULTS: The chemokine receptors CXCR3, CXCR5, CCR5, and CCR7 were detected on CD19(+) cells isolated from the brain during MCMV infection. In particular, CXCR3 was found to be elevated on an increasing number of cells over the time course of infection, and it was the primary chemokine receptor expressed at 60 days post infection Quite different expression kinetics were observed for CXCR5, CCR5, and CCR7, which were elevated on the highest number of cells early during infection and decreased by 14, 30, and 60 days post infection Correspondingly, elevated levels of CXCL9, CXCL10, and CXCL13, as well as CCL5, were found within the brains of infected animals, and only low levels of CCL3 and CCL19 were detected. Differential expression of CXCL9/CXCL10 and CXCL13 between microglia and astrocytes was apparent, and B cells moved towards supernatants from MCMV-infected microglia, but not astrocytes. Pretreatment with neutralizing Abs to CXCL9 and CXCL10 inhibited this migration. In contrast, neutralizing Abs to the ligand of CXCR5 (i.e., CXCL13) did not significantly block chemotaxis. Proliferation of brain-infiltrating B cells was detected at 7 days post infection and persisted through the latest time tested (60 days post infection). Finally, astrocytes produce BAFF (B cell activating factor of the TNF family) and promote proliferation of B cells via cell-to-cell contact. CONCLUSIONS: CXCR3 is the primary chemokine receptor on CD19(+) B cells persisting within the brain, and migration to microglial cell supernatants is mediated through this receptor. Correspondingly, microglial cells produce CXCL9 and CXCL10, but not CXCL13. Reactive astrocytes promote B cell proliferation.",2016 May 20,"['Lokensgard, James R.', 'Mutnal, Manohar B.', 'Prasad, Sujata', 'Sheng, Wen', 'Hu, Shuxian']",J Neuroinflammation,,,True
7c8655ffbfd16f13266b635a0a9f907579f0969d,PMC,Resveratrol attenuates cortical neuron activity: roles of large conductance calcium-activated potassium channels and voltage-gated sodium channels,http://dx.doi.org/10.1186/s12929-016-0259-y,PMC4875746,27209372,CC BY,"BACKGROUND: Resveratrol, a phytoalexin found in grapes and red wine, exhibits diverse pharmacological activities. However, relatively little is known about whether resveratrol modulates the ion channels in cortical neurons. The large-conductance calcium-activated potassium channels (BK(Ca)) and voltage-gated sodium channels were expressed in cortical neurons and play important roles in regulation of neuronal excitability. The present study aimed to determine the effects of resveratrol on BK(Ca) currents and voltage-gated sodium currents in cortical neurons. RESULTS: Resveratrol concentration-dependently increased the current amplitude and the opening activity of BK(Ca) channels, but suppressed the amplitude of voltage-gated sodium currents. Similar to the BK(Ca) channel opener NS1619, resveratrol decreased the firing rate of action potentials. In addition, the enhancing effects of BK(Ca) channel blockers tetraethylammonium (TEA) and paxilline on action potential firing were sensitive to resveratrol. Our results indicated that the attenuation of action potential firing rate by resveratrol might be mediated through opening the BK(Ca) channels and closing the voltage-gated sodium channels. CONCLUSIONS: As BK(Ca) channels and sodium channels are critical molecular determinants for seizure generation, our findings suggest that regulation of these two channels in cortical neurons probably makes a considerable contribution to the antiseizure activity of resveratrol.",2016 May 21,"['Wang, Ya-Jean', 'Chan, Ming-Huan', 'Chen, Linyi', 'Wu, Sheng-Nan', 'Chen, Hwei-Hisen']",J Biomed Sci,,,True
2c092e37343c79101dfbf1f9f66a87f569432a29,PMC,Reverse transcription strand invasion based amplification (RT-SIBA): a method for rapid detection of influenza A and B,http://dx.doi.org/10.1007/s00253-016-7491-y,PMC4875950,27063012,CC BY,"Rapid and accurate diagnosis of influenza viruses plays an important role in infection control, as well as in preventing the misuse of antibiotics. Isothermal nucleic acid amplification methods offer significant advantages over the polymerase chain reaction (PCR), since they are more rapid and do not require the sophisticated instruments needed for thermal cycling. We previously described a novel isothermal nucleic acid amplification method, ‘Strand Invasion Based Amplification’ (SIBA®), with high analytical sensitivity and specificity, for the detection of DNA. In this study, we describe the development of a variant of the SIBA method, namely, reverse transcription SIBA (RT-SIBA), for the rapid detection of viral RNA targets. The RT-SIBA method includes a reverse transcriptase enzyme that allows one-step reverse transcription of RNA to complementary DNA (cDNA) and simultaneous amplification and detection of the cDNA by SIBA under isothermal reaction conditions. The RT-SIBA method was found to be more sensitive than PCR for the detection of influenza A and B and could detect 100 copies of influenza RNA within 15 min. The development of RT-SIBA will enable rapid and accurate diagnosis of viral RNA targets within point-of-care or central laboratory settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-016-7491-y) contains supplementary material, which is available to authorized users.",2016 Apr 11,"['Eboigbodin, Kevin', 'Filén, Sanna', 'Ojalehto, Tuomas', 'Brummer, Mirko', 'Elf, Sonja', 'Pousi, Kirsi', 'Hoser, Mark']",Appl Microbiol Biotechnol,,,False
4ef86c928be12807b78ebc327eb41f0380cf0b75,PMC,Reverse transcription strand invasion based amplification (RT-SIBA): a method for rapid detection of influenza A and B,http://dx.doi.org/10.1007/s00253-016-7491-y,PMC4875950,27063012,CC BY,"Rapid and accurate diagnosis of influenza viruses plays an important role in infection control, as well as in preventing the misuse of antibiotics. Isothermal nucleic acid amplification methods offer significant advantages over the polymerase chain reaction (PCR), since they are more rapid and do not require the sophisticated instruments needed for thermal cycling. We previously described a novel isothermal nucleic acid amplification method, ‘Strand Invasion Based Amplification’ (SIBA®), with high analytical sensitivity and specificity, for the detection of DNA. In this study, we describe the development of a variant of the SIBA method, namely, reverse transcription SIBA (RT-SIBA), for the rapid detection of viral RNA targets. The RT-SIBA method includes a reverse transcriptase enzyme that allows one-step reverse transcription of RNA to complementary DNA (cDNA) and simultaneous amplification and detection of the cDNA by SIBA under isothermal reaction conditions. The RT-SIBA method was found to be more sensitive than PCR for the detection of influenza A and B and could detect 100 copies of influenza RNA within 15 min. The development of RT-SIBA will enable rapid and accurate diagnosis of viral RNA targets within point-of-care or central laboratory settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-016-7491-y) contains supplementary material, which is available to authorized users.",2016 Apr 11,"['Eboigbodin, Kevin', 'Filén, Sanna', 'Ojalehto, Tuomas', 'Brummer, Mirko', 'Elf, Sonja', 'Pousi, Kirsi', 'Hoser, Mark']",Appl Microbiol Biotechnol,,,True
8303edd7c319344d34223d60c9578385684a7f28,PMC,Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene,http://dx.doi.org/10.1038/srep26311,PMC4876326,27212633,CC BY,"Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.",2016 May 23,"['Schobel, Seth A.', 'Stucker, Karla M.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Larkin, Emma K.', 'Shankar, Jyoti', 'Bera, Jayati', 'Puri, Vinita', 'Shilts, Meghan H.', 'Rosas-Salazar, Christian', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Shrivastava, Susmita', 'Stockwell, Timothy B.', 'Peebles, R. Stokes', 'Hartert, Tina V.', 'Das, Suman R.']",Sci Rep,,,True
8ccc3179663909f2288db1287ef94906fb03d3b7,PMC,Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene,http://dx.doi.org/10.1038/srep26311,PMC4876326,27212633,CC BY,"Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.",2016 May 23,"['Schobel, Seth A.', 'Stucker, Karla M.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Larkin, Emma K.', 'Shankar, Jyoti', 'Bera, Jayati', 'Puri, Vinita', 'Shilts, Meghan H.', 'Rosas-Salazar, Christian', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Shrivastava, Susmita', 'Stockwell, Timothy B.', 'Peebles, R. Stokes', 'Hartert, Tina V.', 'Das, Suman R.']",Sci Rep,,,False
88e54a41da94777eb018ae7915e92f5ad28cf706,PMC,Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene,http://dx.doi.org/10.1038/srep26311,PMC4876326,27212633,CC BY,"Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.",2016 May 23,"['Schobel, Seth A.', 'Stucker, Karla M.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Larkin, Emma K.', 'Shankar, Jyoti', 'Bera, Jayati', 'Puri, Vinita', 'Shilts, Meghan H.', 'Rosas-Salazar, Christian', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Shrivastava, Susmita', 'Stockwell, Timothy B.', 'Peebles, R. Stokes', 'Hartert, Tina V.', 'Das, Suman R.']",Sci Rep,,,False
de7726a88ffb639c59dcdec8eb0f76501c56c96c,PMC,Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene,http://dx.doi.org/10.1038/srep26311,PMC4876326,27212633,CC BY,"Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.",2016 May 23,"['Schobel, Seth A.', 'Stucker, Karla M.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Larkin, Emma K.', 'Shankar, Jyoti', 'Bera, Jayati', 'Puri, Vinita', 'Shilts, Meghan H.', 'Rosas-Salazar, Christian', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Shrivastava, Susmita', 'Stockwell, Timothy B.', 'Peebles, R. Stokes', 'Hartert, Tina V.', 'Das, Suman R.']",Sci Rep,,,False
bf3e0264c05ee78d66269189d8ed448bc13d4b62,PMC,Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene,http://dx.doi.org/10.1038/srep26311,PMC4876326,27212633,CC BY,"Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.",2016 May 23,"['Schobel, Seth A.', 'Stucker, Karla M.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Larkin, Emma K.', 'Shankar, Jyoti', 'Bera, Jayati', 'Puri, Vinita', 'Shilts, Meghan H.', 'Rosas-Salazar, Christian', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Shrivastava, Susmita', 'Stockwell, Timothy B.', 'Peebles, R. Stokes', 'Hartert, Tina V.', 'Das, Suman R.']",Sci Rep,,,False
bdd2c70f5e1dd38c3983adeac033665b7ac56909,PMC,Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene,http://dx.doi.org/10.1038/srep26311,PMC4876326,27212633,CC BY,"Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.",2016 May 23,"['Schobel, Seth A.', 'Stucker, Karla M.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Larkin, Emma K.', 'Shankar, Jyoti', 'Bera, Jayati', 'Puri, Vinita', 'Shilts, Meghan H.', 'Rosas-Salazar, Christian', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Shrivastava, Susmita', 'Stockwell, Timothy B.', 'Peebles, R. Stokes', 'Hartert, Tina V.', 'Das, Suman R.']",Sci Rep,,,False
151fe22ecfaef4184f29724d622cce8012ee0b50,PMC,Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene,http://dx.doi.org/10.1038/srep26311,PMC4876326,27212633,CC BY,"Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.",2016 May 23,"['Schobel, Seth A.', 'Stucker, Karla M.', 'Moore, Martin L.', 'Anderson, Larry J.', 'Larkin, Emma K.', 'Shankar, Jyoti', 'Bera, Jayati', 'Puri, Vinita', 'Shilts, Meghan H.', 'Rosas-Salazar, Christian', 'Halpin, Rebecca A.', 'Fedorova, Nadia', 'Shrivastava, Susmita', 'Stockwell, Timothy B.', 'Peebles, R. Stokes', 'Hartert, Tina V.', 'Das, Suman R.']",Sci Rep,,,False
eaa5563d3b1791ebb166e18abfaba4e22b965049,PMC,The scanning electron microscope in microbiology and diagnosis of infectious disease,http://dx.doi.org/10.1038/srep26516,PMC4876401,27212232,CC BY,"Despite being an excellent tool for investigating ultrastructure, scanning electron microscopy (SEM) is less frequently used than transmission electron microscopy for microbes such as viruses or bacteria. Here we describe rapid methods that allow SEM imaging of fully hydrated, unfixed microbes without using conventional sample preparation methods. We demonstrate improved ultrastructural preservation, with greatly reduced dehydration and shrinkage, for specimens including bacteria and viruses such as Ebola virus using infiltration with ionic liquid on conducting filter substrates for SEM.",2016 May 23,"['Golding, Christine G.', 'Lamboo, Lindsey L.', 'Beniac, Daniel R.', 'Booth, Timothy F.']",Sci Rep,,,True
8766e2b5d1ae6c890710a3c8bccd1321d15db79f,PMC,The scanning electron microscope in microbiology and diagnosis of infectious disease,http://dx.doi.org/10.1038/srep26516,PMC4876401,27212232,CC BY,"Despite being an excellent tool for investigating ultrastructure, scanning electron microscopy (SEM) is less frequently used than transmission electron microscopy for microbes such as viruses or bacteria. Here we describe rapid methods that allow SEM imaging of fully hydrated, unfixed microbes without using conventional sample preparation methods. We demonstrate improved ultrastructural preservation, with greatly reduced dehydration and shrinkage, for specimens including bacteria and viruses such as Ebola virus using infiltration with ionic liquid on conducting filter substrates for SEM.",2016 May 23,"['Golding, Christine G.', 'Lamboo, Lindsey L.', 'Beniac, Daniel R.', 'Booth, Timothy F.']",Sci Rep,,,False
698174035746c185ce55489b4a345026d82dcc42,PMC,Transcriptional Analysis of PRRSV-Infected Porcine Dendritic Cell Response to Streptococcus suis Infection Reveals Up-Regulation of Inflammatory-Related Genes Expression,http://dx.doi.org/10.1371/journal.pone.0156019,PMC4877111,27213692,CC BY,"The porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important swine pathogens and often serves as an entry door for other viral or bacterial pathogens, of which Streptococcus suis is one of the most common. Pre-infection with PRRSV leads to exacerbated disease caused by S. suis infection. Very few studies have assessed the immunological mechanisms underlying this higher susceptibility. Since antigen presenting cells play a major role in the initiation of the immune response, the in vitro transcriptional response of bone marrow-derived dendritic cells (BMDCs) and monocytes in the context of PRRSV and S. suis co-infection was investigated. BMDCs were found to be more permissive than monocytes to PRRSV infection; S. suis phagocytosis by PRRSV-infected BMDCs was found to be impaired, whereas no effect was found on bacterial intracellular survival. Transcription profile analysis, with a major focus on inflammatory genes, following S. suis infection, with and without pre-infection with PRRSV, was then performed. While PRRSV pre-infection had little effect on monocytes response to S. suis infection, a significant expression of several pro-inflammatory molecules was observed in BMDCs pre-infected with PRRSV after a subsequent infection with S. suis. While an additive effect could be observed for CCL4, CCL14, CCL20, and IL-15, a distinct synergistic up-regulatory effect was observed for IL-6, CCL5 and TNF-α after co-infection. This increased pro-inflammatory response by DCs could participate in the exacerbation of the disease observed during PRRSV and S. suis co-infection.",2016 May 23,"['Auray, Gaël', 'Lachance, Claude', 'Wang, Yingchao', 'Gagnon, Carl A.', 'Segura, Mariela', 'Gottschalk, Marcelo']",PLoS One,,,True
59d3f98d78f2ff993174b173807435e75df8bc3a,PMC,Evidence for widespread infection of African bats with Crimean-Congo hemorrhagic fever-like viruses,http://dx.doi.org/10.1038/srep26637,PMC4877572,27217069,CC BY,"Crimean Congo hemorrhagic fever virus (CCHFV) is a highly virulent tick-borne pathogen that causes hemorrhagic fever in humans. The geographic range of human CCHF cases largely reflects the presence of ticks. However, highly similar CCHFV lineages occur in geographically distant regions. Tick-infested migratory birds have been suggested, but not confirmed, to contribute to the dispersal. Bats have recently been shown to carry nairoviruses distinct from CCHFV. In order to assess the presence of CCHFV in a wide range of bat species over a wide geographic range, we analyzed 1,135 sera from 16 different bat species collected in Congo, Gabon, Ghana, Germany, and Panama. Using a CCHFV glycoprotein-based indirect immunofluorescence test (IIFT), we identified reactive antibodies in 10.0% (114/1,135) of tested bats, pertaining to 12/16 tested species. Depending on the species, 3.6%–42.9% of cave-dwelling bats and 0.6%–7.1% of foliage-living bats were seropositive (two-tailed t-test, p = 0.0447 cave versus foliage). 11/30 IIFT-reactive sera from 10 different African bat species had neutralizing activity in a virus-like particle assay. Neutralization of full CCHFV was confirmed in 5 of 7 sera. Widespread infection of cave-dwelling bats may indicate a role for bats in the life cycle and geographic dispersal of CCHFV.",2016 May 24,"['Müller, Marcel A.', 'Devignot, Stéphanie', 'Lattwein, Erik', 'Corman, Victor Max', 'Maganga, Gaël D.', 'Gloza-Rausch, Florian', 'Binger, Tabea', 'Vallo, Peter', 'Emmerich, Petra', 'Cottontail, Veronika M.', 'Tschapka, Marco', 'Oppong, Samuel', 'Drexler, Jan Felix', 'Weber, Friedemann', 'Leroy, Eric M.', 'Drosten, Christian']",Sci Rep,,,True
62406757c331d6c939bf09fa005bb565b3fac0b9,PMC,Lack of transmission among healthcare workers in contact with a case of Middle East respiratory syndrome coronavirus infection in Thailand,http://dx.doi.org/10.1186/s13756-016-0120-9,PMC4877934,27222710,CC BY,"INTRODUCTION: A hospital-associated outbreak of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was reported. We aimed to assess the effectiveness of infection control measures among healthcare workers (HCWs) who were exposed to a MERS patient and/or his body fluids in our institute. METHODS: A descriptive study was conducted among HCWs who worked with a MERS patient in Bamrasnaradura Infectious Diseases Institute, Thailand, between 18 June and 3 July 2015. Contacts were defined as HCWs who worked in the patient’s room or with the patient’s body fluids. Serum samples from all contacts were collected within 14 days of last contact and one month later. Paired sera were tested for detection of MERS‐CoV antibodies by using an indirect ELISA. RESULTS: Thirty-eight (88.4 %) of 43 identified contacts consented to enroll. The mean (SD) age was 38.1 (11.1) years, and 79 % were females. The median (IQR) cumulative duration of work of HCWs in the patient’s room was 35 (20–165) minutes. The median (IQR) cumulative duration of work of HCWs with the patient’s blood or body fluids in laboratory was 67.5 (43.7–117.5) minutes. All contacts reported 100 % compliance with hand hygiene, using N95 respirator, performing respirator fit test, wearing gown, gloves, eye protection, and cap during their entire working period. All serum specimens of contacts tested for MERS-CoV antibodies were negative. CONCLUSIONS: We provide evidence of effective infection control practices against MERS-CoV transmission in a healthcare facility. Strict infection control precautions can protect HCWs. The optimal infection control measures for MERS-CoV should be further evaluated.",2016 May 23,"['Wiboonchutikul, Surasak', 'Manosuthi, Weerawat', 'Likanonsakul, Sirirat', 'Sangsajja, Chariya', 'Kongsanan, Paweena', 'Nitiyanontakij, Ravee', 'Thientong, Varaporn', 'Lerdsamran, Hatairat', 'Puthavathana, Pilaipan']",Antimicrob Resist Infect Control,,,True
63cfe8fa64e33300471ac1e2a5b87cb52be553d9,PMC,A de novo transcriptome analysis shows that modulation of the JAK-STAT signaling pathway by salmonid alphavirus subtype 3 favors virus replication in macrophage/dendritic-like TO-cells,http://dx.doi.org/10.1186/s12864-016-2739-6,PMC4878077,27215196,CC BY,"BACKGROUND: The Janus kinase (Jak) and signaling transducer activator of transcription (Stat) pathway mediates the signaling of genes required for cellular development and homeostasis. To elucidate the effect of type I IFN on the Jak/stat pathway in salmonid alphavirus subtype 3 (SAV3) infected macrophage/dendritic like TO-cells derived from Atlantic salmon (Salmo salar L) headkidney leukocytes, we used a differential transcriptome analysis by RNA-seq and the Kyoto encyclopedia of genes and genomes (KEGGs) pathway analysis to generate a repertoire of de novo assembled genes from type I IFN treated and non-treated TO-cells infected with SAV3. RESULTS: Concurrent SAV3 infection with type I IFN treatment of TO-cells suppressed SAV3 structural protein (SP) expression by 2log(10) at 2 days post infection compared to SAV3 infection without IFN treatment which paved way to evaluating the impact of type I IFN on expression of Jak/stat pathway genes in SAV3 infected TO-cells. In the absence of type I IFN treatment, SAV3 downregulated several Jak/stat pathway genes that included type I and II receptor genes, Jak2, tyrosine kinase 2 (Tyk2), Stat3 and Stat5 pointing to possible failure to activate the Jak/stat signaling pathway and inhibition of signal transducers caused by SAV3 infection. Although the suppressor of cytokine signaling (SOCS) genes 1 and 3 were upregulated in the IFN treated cells, only SOCS3 was downregulated in the SAV3 infected cells which points to inhibition of SOCS3 by SAV3 infection in TO-cells. CONCLUSION: Data presented in this study shows that SAV3 infection downregulates several genes of the Jak/stat pathway, which could be an immune evasion strategy, used to block the transcription of antiviral genes that would interfere with SAV3 replication in TO-cells. Overall, we have shown that combining de novo assembly with pathway based transcriptome analyses provides a contextual approach to understanding the molecular networks of genes that form the Jak/stat pathway in TO-cells infected by SAV3.",2016 May 23,"['Xu, Cheng', 'Evensen, Øystein', 'Munang’andu, Hetron Mweemba']",BMC Genomics,,,True
c2749a18c00e1668167a5f65d6d9ff7896f25465,PMC,Respiratory syncytial virus seasonality in Brazil: implications for the immunisation policy for at-risk populations,http://dx.doi.org/10.1590/0074-02760150341,PMC4878298,27120006,CC BY,"Respiratory syncytial virus (RSV) infection is the leading cause of hospitalisation for respiratory diseases among children under 5 years old. The aim of this study was to analyse RSV seasonality in the five distinct regions of Brazil using time series analysis (wavelet and Fourier series) of the following indicators: monthly positivity of the immunofluorescence reaction for RSV identified by virologic surveillance system, and rate of hospitalisations per bronchiolitis and pneumonia due to RSV in children under 5 years old (codes CID-10 J12.1, J20.5, J21.0 and J21.9). A total of 12,501 samples with 11.6% positivity for RSV (95% confidence interval 11 - 12.2), varying between 7.1 and 21.4% in the five Brazilian regions, was analysed. A strong trend for annual cycles with a stable stationary pattern in the five regions was identified through wavelet analysis of the indicators. The timing of RSV activity by Fourier analysis was similar between the two indicators analysed and showed regional differences. This study reinforces the importance of adjusting the immunisation period for high risk population with the monoclonal antibody palivizumab taking into account regional differences in seasonality of RSV.",2016 May,"['Freitas, André Ricardo Ribas', 'Donalisio, Maria Rita']",Mem Inst Oswaldo Cruz,,,True
8b221945f093d8d13835556a56c2a1d8f02e2705,PMC,Innate Immune Responses in ALV-J Infected Chicks and Chickens with Hemangioma In Vivo,http://dx.doi.org/10.3389/fmicb.2016.00786,PMC4879323,27252695,CC BY,"Avian leukosis virus subgroup J (ALV-J) infection can cause tumors and immunosuppression. Since the precise mechanism of the innate immune response induced by ALV-J is unknown, we investigated the antiviral innate immune responses induced by ALV-J in chicks and chickens that had developed tumors. Spleen levels of interleukin-6 (IL-6), IL-10, IL-1β, and interferon-β (IFN-β) were not significantly different between the infected chick groups and the control groups from 1 day post hatch to 7 days post hatch. However, IL-6, IL-1β, and IFN-β protein levels in the three clinical samples with hemangiomas were dramatically increased compared to the healthy samples. In addition, the anti-inflammatory cytokine IL-10 increased sharply in two of three clinical samples. We also found a more than 20-fold up-regulation of ISG12-1 mRNA at 1 day post infection (d.p.i.) and a twofold up-regulation of ZC3HAV1 mRNA at 4 d.p.i. However, there were no statistical differences in ISG12-1 and ZC3HAV1 mRNA expression levels in the tumorigenesis phase. ALV-J infection induced a significant increase of Toll-like receptor 7 (TLR-7) at 1 d.p.i. and dramatically increased the mRNA levels of melanoma differentiation-associated gene 5 (MDA5) in the tumorigenesis phase. Moreover, the protein levels of interferon regulatory factor 1 (IRF-1) and signal transducer and activator of transcription 1 (STAT1) were decreased in chickens with tumors. These results suggest that ALV-J was primarily recognized by chicken TLR7 and MDA5 at early and late in vivo infection stages, respectively. ALV-J strain SCAU-HN06 did not induce any significant antiviral innate immune response in 1 week old chicks. However, interferon-stimulated genes were not induced normally during the late phase of ALV-J infection due to a reduction of IRF1 and STAT1 expression.",2016 May 25,"['Feng, Min', 'Dai, Manman', 'Xie, Tingting', 'Li, Zhenhui', 'Shi, Meiqing', 'Zhang, Xiquan']",Front Microbiol,,,True
6518eb44df3244c513ccb0ceea5b7f3eb3dd9b52,PMC,Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing,http://dx.doi.org/10.1038/srep26017,PMC4879520,27221218,CC BY,"Emerging and re-emerging infectious diseases caused by RNA viruses pose a critical public health threat. Next generation sequencing (NGS) is a powerful technology to define genomic sequences of the viruses. Of particular interest is the use of whole genome sequencing (WGS) to perform phylogeographic analysis, that allows the detection and tracking of the emergence of viral infections. Hantaviruses, Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans. We propose to use WGS for the phylogeographic analysis of human hantavirus infections. A novel multiplex PCR-based NGS was developed to gather whole genome sequences of Hantaan virus (HTNV) from HFRS patients and rodent hosts in endemic areas. The obtained genomes were described for the spatial and temporal links between cases and their sources. Phylogenetic analyses demonstrated geographic clustering of HTNV strains from clinical specimens with the HTNV strains circulating in rodents, suggesting the most likely site and time of infection. Recombination analysis demonstrated a genome organization compatible with recombination of the HTNV S segment. The multiplex PCR-based NGS is useful and robust to acquire viral genomic sequences and may provide important ways to define the phylogeographical association and molecular evolution of hantaviruses.",2016 May 25,"['Kim, Won-Keun', 'Kim, Jeong-Ah', 'Song, Dong Hyun', 'Lee, Daesang', 'Kim, Yong Chul', 'Lee, Sook-Young', 'Lee, Seung-Ho', 'No, Jin Sun', 'Kim, Ji Hye', 'Kho, Jeong Hoon', 'Gu, Se Hun', 'Jeong, Seong Tae', 'Wiley, Michael', 'Kim, Heung-Chul', 'Klein, Terry A.', 'Palacios, Gustavo', 'Song, Jin-Won']",Sci Rep,,,True
27052d6e2693fe9dfae4a746408e16180ed57243,PMC,Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing,http://dx.doi.org/10.1038/srep26017,PMC4879520,27221218,CC BY,"Emerging and re-emerging infectious diseases caused by RNA viruses pose a critical public health threat. Next generation sequencing (NGS) is a powerful technology to define genomic sequences of the viruses. Of particular interest is the use of whole genome sequencing (WGS) to perform phylogeographic analysis, that allows the detection and tracking of the emergence of viral infections. Hantaviruses, Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans. We propose to use WGS for the phylogeographic analysis of human hantavirus infections. A novel multiplex PCR-based NGS was developed to gather whole genome sequences of Hantaan virus (HTNV) from HFRS patients and rodent hosts in endemic areas. The obtained genomes were described for the spatial and temporal links between cases and their sources. Phylogenetic analyses demonstrated geographic clustering of HTNV strains from clinical specimens with the HTNV strains circulating in rodents, suggesting the most likely site and time of infection. Recombination analysis demonstrated a genome organization compatible with recombination of the HTNV S segment. The multiplex PCR-based NGS is useful and robust to acquire viral genomic sequences and may provide important ways to define the phylogeographical association and molecular evolution of hantaviruses.",2016 May 25,"['Kim, Won-Keun', 'Kim, Jeong-Ah', 'Song, Dong Hyun', 'Lee, Daesang', 'Kim, Yong Chul', 'Lee, Sook-Young', 'Lee, Seung-Ho', 'No, Jin Sun', 'Kim, Ji Hye', 'Kho, Jeong Hoon', 'Gu, Se Hun', 'Jeong, Seong Tae', 'Wiley, Michael', 'Kim, Heung-Chul', 'Klein, Terry A.', 'Palacios, Gustavo', 'Song, Jin-Won']",Sci Rep,,,False
b971e1834336cb9157841f3e501b68a7031ff518,PMC,Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing,http://dx.doi.org/10.1038/srep26017,PMC4879520,27221218,CC BY,"Emerging and re-emerging infectious diseases caused by RNA viruses pose a critical public health threat. Next generation sequencing (NGS) is a powerful technology to define genomic sequences of the viruses. Of particular interest is the use of whole genome sequencing (WGS) to perform phylogeographic analysis, that allows the detection and tracking of the emergence of viral infections. Hantaviruses, Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans. We propose to use WGS for the phylogeographic analysis of human hantavirus infections. A novel multiplex PCR-based NGS was developed to gather whole genome sequences of Hantaan virus (HTNV) from HFRS patients and rodent hosts in endemic areas. The obtained genomes were described for the spatial and temporal links between cases and their sources. Phylogenetic analyses demonstrated geographic clustering of HTNV strains from clinical specimens with the HTNV strains circulating in rodents, suggesting the most likely site and time of infection. Recombination analysis demonstrated a genome organization compatible with recombination of the HTNV S segment. The multiplex PCR-based NGS is useful and robust to acquire viral genomic sequences and may provide important ways to define the phylogeographical association and molecular evolution of hantaviruses.",2016 May 25,"['Kim, Won-Keun', 'Kim, Jeong-Ah', 'Song, Dong Hyun', 'Lee, Daesang', 'Kim, Yong Chul', 'Lee, Sook-Young', 'Lee, Seung-Ho', 'No, Jin Sun', 'Kim, Ji Hye', 'Kho, Jeong Hoon', 'Gu, Se Hun', 'Jeong, Seong Tae', 'Wiley, Michael', 'Kim, Heung-Chul', 'Klein, Terry A.', 'Palacios, Gustavo', 'Song, Jin-Won']",Sci Rep,,,False
46db8b3db38acf771fe27031fee9445b99146308,PMC,Epigenetic Effect of Environmental Factors on Autism Spectrum Disorders,http://dx.doi.org/10.3390/ijerph13050504,PMC4881129,27187441,CC BY,"Both environmental factors and genetic factors are involved in the pathogenesis of autism spectrum disorders (ASDs). Epigenetics, an essential mechanism for gene regulation based on chemical modifications of DNA and histone proteins, is also involved in congenital ASDs. It was recently demonstrated that environmental factors, such as endocrine disrupting chemicals and mental stress in early life, can change epigenetic status and gene expression, and can cause ASDs. Moreover, environmentally induced epigenetic changes are not erased during gametogenesis and are transmitted to subsequent generations, leading to changes in behavior phenotypes. However, epigenetics has a reversible nature since it is based on the addition or removal of chemical residues, and thus the original epigenetic status may be restored. Indeed, several antidepressants and anticonvulsants used for mental disorders including ASDs restore the epigenetic state and gene expression. Therefore, further epigenetic understanding of ASDs is important for the development of new drugs that take advantages of epigenetic reversibility.",2016 May 14,"['Kubota, Takeo', 'Mochizuki, Kazuki']",Int J Environ Res Public Health,,,True
588631c5434bdc11922450678d5d65823f62e432,PMC,A Brief Review of Computer-Assisted Approaches to Rational Design of Peptide Vaccines,http://dx.doi.org/10.3390/ijms17050666,PMC4881492,27153063,CC BY,"The growing incidences of new viral diseases and increasingly frequent viral epidemics have strained therapeutic and preventive measures; the high mutability of viral genes puts additional strains on developmental efforts. Given the high cost and time requirements for new drugs development, vaccines remain as a viable alternative, but there too traditional techniques of live-attenuated or inactivated vaccines have the danger of allergenic reactions and others. Peptide vaccines have, over the last several years, begun to be looked on as more appropriate alternatives, which are economically affordable, require less time for development and hold the promise of multi-valent dosages. The developments in bioinformatics, proteomics, immunogenomics, structural biology and other sciences have spurred the growth of vaccinomics where computer assisted approaches serve to identify suitable peptide targets for eventual development of vaccines. In this mini-review we give a brief overview of some of the recent trends in computer assisted vaccine development with emphasis on the primary selection procedures of probable peptide candidates for vaccine development.",2016 May 4,"['Nandy, Ashesh', 'Basak, Subhash C.']",Int J Mol Sci,,,True
d117c8256785f2ff80a40fba878aa4f022d8310b,PMC,SARS Coronavirus Papain-Like Protease Inhibits the TLR7 Signaling Pathway through Removing Lys63-Linked Polyubiquitination of TRAF3 and TRAF6,http://dx.doi.org/10.3390/ijms17050678,PMC4881504,27164085,CC BY,"Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLPro) reportedly inhibits the production of type I interferons (IFNs) and pro-inflammatory cytokines in Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene 1 (RIG-I) pathways. The study investigated the inhibitory effect and its antagonistic mechanism of SARS-CoV PLPro on TLR7-mediated cytokine production. TLR7 agonist (imiquimod (IMQ)) concentration-dependently induced activation of ISRE-, NF-κB- and AP-1-luciferase reporters, as well as the production of IFN-α, IFN-β, TNF-α, IL-6 and IL-8 in human promonocyte cells. However, SARS-CoV PLPro significantly inhibited IMQ-induced cytokine production through suppressing the activation of transcription factors IRF-3, NF-κB and AP-1. Western blot analysis with anti-Lys48 and anti-Lys63 ubiquitin antibodies indicated the SARS-CoV PLPro removed Lys63-linked ubiquitin chains of TRAF3 and TRAF6, but not Lys48-linked ubiquitin chains in un-treated and treated cells. The decrease in the activated state of TRAF3 and TRAF6 correlated with the inactivation of TBK1 in response to IMQ by PLPro. The results revealed that the antagonism of SARS-CoV PLPro on TLR7-mediated innate immunity was associated with the negative regulation of TRAF3/6-TBK1-IRF3/NF-κB/AP1 signals.",2016 May 5,"['Li, Shih-Wen', 'Wang, Ching-Ying', 'Jou, Yu-Jen', 'Huang, Su-Hua', 'Hsiao, Li-Hsin', 'Wan, Lei', 'Lin, Ying-Ju', 'Kung, Szu-Hao', 'Lin, Cheng-Wen']",Int J Mol Sci,,,True
13e902f62fb20b66fbbc69e9ec434243342d16cd,PMC,Isolation and Characterization of Dromedary Camel Coronavirus UAE-HKU23 from Dromedaries of the Middle East: Minimal Serological Cross-Reactivity between MERS Coronavirus and Dromedary Camel Coronavirus UAE-HKU23,http://dx.doi.org/10.3390/ijms17050691,PMC4881517,27164099,CC BY,"Recently, we reported the discovery of a dromedary camel coronavirus UAE-HKU23 (DcCoV UAE-HKU23) from dromedaries in the Middle East. In this study, DcCoV UAE-HKU23 was successfully isolated in two of the 14 dromedary fecal samples using HRT-18G cells, with cytopathic effects observed five days after inoculation. Northern blot analysis revealed at least seven distinct RNA species, corresponding to predicted subgenomic mRNAs and confirming the core sequence of transcription regulatory sequence motifs as 5′-UCUAAAC-3′ as we predicted previously. Antibodies against DcCoV UAE-HKU23 were detected in 58 (98.3%) and 59 (100%) of the 59 dromedary sera by immunofluorescence and neutralization antibody tests, respectively. There was significant correlation between the antibody titers determined by immunofluorescence and neutralization assays (Pearson coefficient = 0.525, p < 0.0001). Immunization of mice using recombinant N proteins of DcCoV UAE-HKU23 and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively, and heat-inactivated DcCoV UAE-HKU23 showed minimal cross-antigenicity between DcCoV UAE-HKU23 and MERS-CoV by Western blot and neutralization antibody assays. Codon usage and genetic distance analysis of RdRp, S and N genes showed that the 14 strains of DcCoV UAE-HKU23 formed a distinct cluster, separated from those of other closely related members of Betacoronavirus 1, including alpaca CoV, confirming that DcCoV UAE-HKU23 is a novel member of Betacoronavirus 1.",2016 May 7,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Fan, Rachel Y. Y.', 'Lau, Candy C. Y.', 'Wong, Emily Y. M.', 'Joseph, Sunitha', 'Tsang, Alan K. L.', 'Wernery, Renate', 'Yip, Cyril C. Y.', 'Tsang, Chi-Ching', 'Wernery, Ulrich', 'Yuen, Kwok-Yung']",Int J Mol Sci,,,True
92f465e2f870b70dfea013a01bc9ccfa46c511de,PMC,Pigment Epithelium-Derived Factor (PEDF) Protects Osteoblastic Cell Line from Glucocorticoid-Induced Apoptosis via PEDF-R,http://dx.doi.org/10.3390/ijms17050730,PMC4881552,27187377,CC BY,"Pigment epithelial-derived factor (PEDF) is known as a widely expressed multifunctional secreted glycoprotein whose biological actions are cell-type dependent. Recent studies demonstrated that PEDF displays cytoprotective activity in several cell types. However, it remains unknown whether PEDF is involved in glucocorticoid-induced osteoblast death. The aim of this study was to examine the role of PEDF in osteoblast survival in response to dexamethasone, an active glucocorticoid analogue, and explore the underlying mechanism. In the present study, dexamethasone (DEX) was used to induce MC3T3-E1 pre-osteoblast apoptosis. PEDF mRNA and protein levels and cell apoptosis were determined respectively. Then PEDF receptor (PEDF-R)- and lysophosphatidic acid (LPA)-related signal transductions were assessed. Here we show that DEX down-regulates PEDF expression, which contributes to osteoblast apoptosis. As a result, exogenous recombinant PEDF (rPEDF) inhibited DEX-induced cell apoptosis. We confirmed that PEDF-R was expressed on MC3T3-E1 pre-osteoblast membrane and could bind to PEDF which increased the level of LPA and activated the phosphorylation of Akt. Our results suggest that PEDF attenuated DEX-induced apoptosis in MC3T3-E1 pre-osteoblasts through LPA-dependent Akt activation via PEDF-R.",2016 May 13,"['Yao, Shengcheng', 'Zhang, Yingnan', 'Wang, Xiaoyu', 'Zhao, Fengchao', 'Sun, Maji', 'Zheng, Xin', 'Dong, Hongyan', 'Guo, Kaijin']",Int J Mol Sci,,,True
7c0168a4b858a8680f305fc4d8cc3c787ff4e110,PMC,Efficient suilysin-mediated invasion and apoptosis in porcine respiratory epithelial cells after streptococcal infection under air-liquid interface conditions,http://dx.doi.org/10.1038/srep26748,PMC4882623,27229328,CC BY,"Streptococci may colonize the epithelium in the airways and other entry sites. While local infection often remains asymptomatic, severe or even fatal diseases occur when streptococci become invasive and spread to different sites in the infected host. We have established porcine respiratory air-liquid interface cultures (ALI) from the porcine lung to analyze the interaction of streptococci with their primary target cells. As representative of the streptococcal family we chose Streptococcus suis (S. suis) that is not only a major swine respiratory pathogen but can also infect humans. Suilysin, a cholesterol-dependent cytolysin (CDC), is an important virulence factor. By comparing a S. suis wt strain with a suilysin-deficient mutant, we demonstrate that suilysin contributes to (i) adherence to airway cells (ii) loss of ciliated cells (iii) apoptosis, and (iv) invasion. Furthermore, we show that cytolytic activity of suilysin is crucial for these effects. A striking result of our analysis was the high efficiency of S. suis-induced apoptosis and invasion upon infection under ALI conditions. These properties have been reported to be less efficient when analyzed with immortalized cells. We hypothesize that soluble effectors such as suilysin are present at higher concentrations in cells kept at ALI conditions and thus more effective. These results should be relevant also for infection of the respiratory tract by other respiratory pathogens.",2016 May 27,"['Meng, Fandan', 'Wu, Nai-Huei', 'Seitz, Maren', 'Herrler, Georg', 'Valentin-Weigand, Peter']",Sci Rep,,,True
b67e67fb94c0a813f6ca3b19aabc69ee7070f8d4,PMC,Efficient suilysin-mediated invasion and apoptosis in porcine respiratory epithelial cells after streptococcal infection under air-liquid interface conditions,http://dx.doi.org/10.1038/srep26748,PMC4882623,27229328,CC BY,"Streptococci may colonize the epithelium in the airways and other entry sites. While local infection often remains asymptomatic, severe or even fatal diseases occur when streptococci become invasive and spread to different sites in the infected host. We have established porcine respiratory air-liquid interface cultures (ALI) from the porcine lung to analyze the interaction of streptococci with their primary target cells. As representative of the streptococcal family we chose Streptococcus suis (S. suis) that is not only a major swine respiratory pathogen but can also infect humans. Suilysin, a cholesterol-dependent cytolysin (CDC), is an important virulence factor. By comparing a S. suis wt strain with a suilysin-deficient mutant, we demonstrate that suilysin contributes to (i) adherence to airway cells (ii) loss of ciliated cells (iii) apoptosis, and (iv) invasion. Furthermore, we show that cytolytic activity of suilysin is crucial for these effects. A striking result of our analysis was the high efficiency of S. suis-induced apoptosis and invasion upon infection under ALI conditions. These properties have been reported to be less efficient when analyzed with immortalized cells. We hypothesize that soluble effectors such as suilysin are present at higher concentrations in cells kept at ALI conditions and thus more effective. These results should be relevant also for infection of the respiratory tract by other respiratory pathogens.",2016 May 27,"['Meng, Fandan', 'Wu, Nai-Huei', 'Seitz, Maren', 'Herrler, Georg', 'Valentin-Weigand, Peter']",Sci Rep,,,False
3f8d3e900290496401f7a6557a64255fdb3ebf0e,PMC,Protective effect of sildenafil on the genotoxicity and cytotoxicity in apolipoprotein E-deficient mice bone marrow cells,http://dx.doi.org/10.1186/s12944-016-0268-6,PMC4882816,27229150,CC BY,"BACKGROUND: The pharmacological inhibitor of phosphodiesterase 5 (PDE5), sildenafil, is a promising candidate for antioxidant therapy that can result in cardiovascular protection. In addition to its known effects on the cardiovascular system, hypercholesterolemia leads to increased oxidative stress and DNA damage in the bone marrow, which is a non-classical target organ of atherosclerosis. In the present study, we evaluate oxidative stress and assess the effect of genomic instability on cell cycle kinetics in atherosclerotic animals and determine if sildenafil reverses these detrimental effects in bone marrow cells. METHODS: Experiments were performed in male wild-type (WT) and apolipoprotein E knockout mice (apoE(−/−)) (9 weeks of age). apoE(−/−) mice were randomly distributed into the following 2 groups: sildenafil-treated (40 mg/kg/day for 3 weeks, n = 8) and vehicle-treated (n = 8), by oral gavage. After treatment, bone marrow cells were isolated to assess the production of superoxide anions and hydrogen peroxide, determine cell cycle kinetics and evaluate the presence of micronucleated cells. RESULTS: Sildenafil treatment reduced the cytoplasmic levels of superoxide anion (~95 % decrease, p < 0.05) and decreased hydrogen peroxide (~30 % decrease, p < 0.05). Moreover, we observed protective effects on the DNA of bone marrow cells, including normal cell cycling, decreased DNA fragmentation and a diminished frequency of micronucleated cells. CONCLUSION: Our data reveal that the excessive production of ROS in atherosclerotic mice overcome the DNA repair pathways in bone marrow cells. The novelty of the present study is that the administration of sildenafil reduced ROS to baseline levels and, consequently, reverted the DNA damage and its outcomes in bone marrow cells.",2016 May 27,"['Bernardes, Franciane P.', 'Batista, Alan T.', 'Porto, Marcella L.', 'Vasquez, Elisardo C.', 'Campagnaro, Bianca P.', 'Meyrelles, Silvana S.']",Lipids Health Dis,,,True
8a3678c3ee2208d7417bfdc62558fe0e32588eab,PMC,Complete Genome Sequence of Porcine Deltacoronavirus Isolated in Thailand in 2015,http://dx.doi.org/10.1128/genomeA.00408-16,PMC4882939,27231358,CC BY,"In Thailand, porcine deltacoronavirus (PDCoV) was first identified in November 2015. The virus was isolated from piglets experiencing diarrhea outbreak. Herein, the full-length genome sequence of the Thai PDCoV isolate P23_15_TT_1115 is reported. The results provide a clearer understanding of the molecular characteristics of PDCoV in Thailand.",2016 May 26,"['Madapong, Adthakorn', 'Saeng-chuto, Kepalee', 'Lorsirigool, Athip', 'Temeeyasen, Gun', 'Srijangwad, Anchalee', 'Tripipat, Thitima', 'Wegner, Matthew', 'Nilubol, Dachrit']",Genome Announc,,,True
6986e55cd9e5fd76339b6a6825b2c3069126555e,PMC,Molecular Epidemiological Investigation of Porcine kobuvirus and Its Coinfection Rate with PEDV and SaV in Northwest China,http://dx.doi.org/10.1155/2016/7590569,PMC4884858,27294133,CC BY,"Porcine kobuvirus (PKV) has circulated throughout China in recent years. Although many studies have detected it throughout the world, its molecular epidemiology has not been characterized in northwest China. To understand its prevalence, 203 fecal samples were collected from different regions of Gansu Province and tested with reverse transcription-polymerase chain reaction. In this study, we tested these samples for PKV, porcine epidemic diarrhea virus (PEDV), and sapovirus and analyzed the amplified 2C gene fragments of PKV. Overall, 126 (62.1%) samples were positive for PKV. Of the 74 piglets samples among the 203 fecal samples, 65 (87.8%) were positive for PKV. PKV infection was often accompanied by PEDV, but the relationship between the two viruses must be confirmed. A phylogenetic analysis indicated that the PKV strains isolated from the same regions clustered on the same branches. This investigation shows that PKV infections are highly prevalent in pigs in northwest China, especially in piglets with symptoms of diarrhea.",2016 May 16,"['Wang, Chen', 'Lan, Xi', 'Yang, Bin']",Biomed Res Int,,,True
0e8773d0887abfa54cb1b618fcdf491e7a0a2c8a,PMC,A Scorpion Defensin BmKDfsin4 Inhibits Hepatitis B Virus Replication in Vitro,http://dx.doi.org/10.3390/toxins8050124,PMC4885039,27128943,CC BY,"Hepatitis B virus (HBV) infection is a major worldwide health problem which can cause acute and chronic hepatitis and can significantly increase the risk of liver cirrhosis and primary hepatocellular carcinoma (HCC). Nowadays, clinical therapies of HBV infection still mainly rely on nucleotide analogs and interferons, the usage of which is limited by drug-resistant mutation or side effects. Defensins had been reported to effectively inhibit the proliferation of bacteria, fungi, parasites and viruses. Here, we screened the anti-HBV activity of 25 scorpion-derived peptides most recently characterized by our group. Through evaluating anti-HBV activity and cytotoxicity, we found that BmKDfsin4, a scorpion defensin with antibacterial and Kv1.3-blocking activities, has a comparable high inhibitory rate of both HBeAg and HBsAg in HepG2.2.15 culture medium and low cytotoxicity to HepG2.2.15. Then, our experimental results further showed that BmKDfsin4 can dose-dependently decrease the production of HBV DNA and HBV viral proteins in both culture medium and cell lysate. Interestingly, BmKDfsin4 exerted high serum stability. Together, this study indicates that the scorpion defensin BmKDfsin4 also has inhibitory activity against HBV replication along with its antibacterial and potassium ion channel Kv1.3-blocking activities, which shows that BmKDfsin4 is a uniquely multifunctional defensin molecule. Our work also provides a good molecule material which will be used to investigate the link or relationship of its antiviral, antibacterial and ion channel–modulating activities in the future.",2016 Apr 27,"['Zeng, Zhengyang', 'Zhang, Qian', 'Hong, Wei', 'Xie, Yingqiu', 'Liu, Yun', 'Li, Wenxin', 'Wu, Yingliang', 'Cao, Zhijian']",Toxins (Basel),,,True
1aac5ef2b73c3c93d866433ce1bb78ee956e2c45,PMC,A Scorpion Defensin BmKDfsin4 Inhibits Hepatitis B Virus Replication in Vitro,http://dx.doi.org/10.3390/toxins8050124,PMC4885039,27128943,CC BY,"Hepatitis B virus (HBV) infection is a major worldwide health problem which can cause acute and chronic hepatitis and can significantly increase the risk of liver cirrhosis and primary hepatocellular carcinoma (HCC). Nowadays, clinical therapies of HBV infection still mainly rely on nucleotide analogs and interferons, the usage of which is limited by drug-resistant mutation or side effects. Defensins had been reported to effectively inhibit the proliferation of bacteria, fungi, parasites and viruses. Here, we screened the anti-HBV activity of 25 scorpion-derived peptides most recently characterized by our group. Through evaluating anti-HBV activity and cytotoxicity, we found that BmKDfsin4, a scorpion defensin with antibacterial and Kv1.3-blocking activities, has a comparable high inhibitory rate of both HBeAg and HBsAg in HepG2.2.15 culture medium and low cytotoxicity to HepG2.2.15. Then, our experimental results further showed that BmKDfsin4 can dose-dependently decrease the production of HBV DNA and HBV viral proteins in both culture medium and cell lysate. Interestingly, BmKDfsin4 exerted high serum stability. Together, this study indicates that the scorpion defensin BmKDfsin4 also has inhibitory activity against HBV replication along with its antibacterial and potassium ion channel Kv1.3-blocking activities, which shows that BmKDfsin4 is a uniquely multifunctional defensin molecule. Our work also provides a good molecule material which will be used to investigate the link or relationship of its antiviral, antibacterial and ion channel–modulating activities in the future.",2016 Apr 27,"['Zeng, Zhengyang', 'Zhang, Qian', 'Hong, Wei', 'Xie, Yingqiu', 'Liu, Yun', 'Li, Wenxin', 'Wu, Yingliang', 'Cao, Zhijian']",Toxins (Basel),,,False
021fba0f252408868fa29b65686dedb3b3d6bf02,PMC,Isolation of the Binding Protein of Periplocoside E from BBMVs in Midgut of the Oriental Amyworm Mythimna separata Walker (Lepidoptera: Noctuidae) through Affinity Chromatography,http://dx.doi.org/10.3390/toxins8050139,PMC4885054,27153092,CC BY,"Periplocosides, which are insecticidal compounds isolated from the root bark of Periploca sepium Bunge, can affect the digestive system of insects. However, the mechanism though which periplocosides induces a series of symptoms remains unknown. In this study, affinity chromatography was conducted by coupling periplocoside E-semi-succinic acid ester with epoxy amino hexyl (EAH) sepharose 4B. Sodium dodecyl sulfonate-polyacrylamide gelelectrophoresis (SDS-PAGE) was performed to analyze the fraction eluted by periplocoside E. Eight binding proteins (luciferin 4-monooxygenase, aminopeptidase N, aminopeptidase N3, nicotinamide adenine dinucleotide health (NADH) dehydrogenase subunit 5, phosphatidylinositol 3-phosphate 3-phosphatase myotubularin, actin, uncharacterized family 31 glucosidase KIAA1161, and 2OG-Fe(2) oxygenase superfamily protein) were obtained and identified through liquid chromatography/quadrupole-time of flight-mass spectrometry (LC/Q-TOF-MS) analysis of the midgut epithelium cells of Mythimna separata larvae. Aminopeptidase N and N3 are potential putative targets of periplocosides. This study establishes the foundation for further research on the mechanism of action and target localization of periplocosides in agricultural pests.",2016 May 4,"['Feng, Mingxing', 'He, Zhenyu', 'Wang, Yuanyuan', 'Yan, Xiufang', 'Zhang, Jiwen', 'Hu, Zhaonong', 'Wu, Wenjun']",Toxins (Basel),,,True
367e3d844bd06915e08d9082a3b720dcc6ac845f,PMC,Dengue Virus Reporter Replicon is a Valuable Tool for Antiviral Drug Discovery and Analysis of Virus Replication Mechanisms,http://dx.doi.org/10.3390/v8050122,PMC4885077,27164125,CC BY,"Dengue, the most prevalent arthropod-borne viral disease, is caused by the dengue virus (DENV), a member of the Flaviviridae family, and is a considerable public health threat in over 100 countries, with 2.5 billion people living in high-risk areas. However, no specific antiviral drug or licensed vaccine currently targets DENV infection. The replicon system has all the factors needed for viral replication in cells. Since the development of replicon systems, transient and stable reporter replicons, as well as reporter viruses, have been used in the study of various virological aspects of DENV and in the identification of DENV inhibitors. In this review, we summarize the DENV reporter replicon system and its applications in high-throughput screening (HTS) for identification of anti-DENV inhibitors. We also describe the use of this system in elucidation of the mechanisms of virus replication and viral dynamics in vivo and in vitro.",2016 May 5,"['Kato, Fumihiro', 'Hishiki, Takayuki']",Viruses,,,True
6df7585dc7616c55baf0dd0df0a8a283f8805acd,PMC,Respiratory Syncytial Virus and Cellular Stress Responses: Impact on Replication and Physiopathology,http://dx.doi.org/10.3390/v8050124,PMC4885079,27187445,CC BY,"Human respiratory syncytial virus (RSV), a member of the Paramyxoviridae family, is a major cause of severe acute lower respiratory tract infection in infants, elderly and immunocompromised adults. Despite decades of research, a complete integrated picture of RSV-host interaction is still missing. Several cellular responses to stress are involved in the host-response to many virus infections. The endoplasmic reticulum stress induced by altered endoplasmic reticulum (ER) function leads to activation of the unfolded-protein response (UPR) to restore homeostasis. Formation of cytoplasmic stress granules containing translationally stalled mRNAs is a means to control protein translation. Production of reactive oxygen species is balanced by an antioxidant response to prevent oxidative stress and the resulting damages. In recent years, ongoing research has started to unveil specific regulatory interactions of RSV with these host cellular stress responses. Here, we discuss the latest findings regarding the mechanisms evolved by RSV to induce, subvert or manipulate the ER stress, the stress granule and oxidative stress responses. We summarize the evidence linking these stress responses with the regulation of RSV replication and the associated pathogenesis.",2016 May 12,"['Cervantes-Ortiz, Sandra L.', 'Zamorano Cuervo, Natalia', 'Grandvaux, Nathalie']",Viruses,,,True
790c6002db87c03cd6bdab85964c52808d09a218,PMC,Applications of Replicating-Competent Reporter-Expressing Viruses in Diagnostic and Molecular Virology,http://dx.doi.org/10.3390/v8050127,PMC4885082,27164126,CC BY,"Commonly used tests based on wild-type viruses, such as immunostaining, cannot meet the demands for rapid detection of viral replication, high-throughput screening for antivirals, as well as for tracking viral proteins or virus transport in real time. Notably, the development of replicating-competent reporter-expressing viruses (RCREVs) has provided an excellent option to detect directly viral replication without the use of secondary labeling, which represents a significant advance in virology. This article reviews the applications of RCREVs in diagnostic and molecular virology, including rapid neutralization tests, high-throughput screening systems, identification of viral receptors and virus-host interactions, dynamics of viral infections in vitro and in vivo, vaccination approaches and others. However, there remain various challenges associated with RCREVs, including pathogenicity alterations due to the insertion of a reporter gene, instability or loss of the reporter gene expression, or attenuation of reporter signals in vivo. Despite all these limitations, RCREVs have become powerful tools for both basic and applied virology with the development of new technologies for generating RCREVs, the inventions of novel reporters and the better understanding of regulation of viral replication.",2016 May 6,"['Li, Yongfeng', 'Li, Lian-Feng', 'Yu, Shaoxiong', 'Wang, Xiao', 'Zhang, Lingkai', 'Yu, Jiahui', 'Xie, Libao', 'Li, Weike', 'Ali, Razim', 'Qiu, Hua-Ji']",Viruses,,,True
a5bfd762a4fb6bdef664818c4e82ca3c718c8862,PMC,Use of Reporter Genes in the Generation of Vaccinia Virus-Derived Vectors,http://dx.doi.org/10.3390/v8050134,PMC4885089,27213433,CC BY,"Vaccinia virus (VACV) is one of the most extensively-studied viruses of the Poxviridae family. It is easy to genetically modify, so it has become a key tool for many applications. In this context, reporter genes facilitate the study of the role of foreign genes introduced into the genome of VACV. In this review, we describe the type of reporter genes that have been used to generate reporter-expressing VACV and the applications of the recombinant viruses obtained. Reporter-expressing VACV are currently employed in basic and immunology research, in the development of vaccines and cancer treatment.",2016 May 21,"['Al Ali, Sally', 'Baldanta, Sara', 'Fernández-Escobar, Mercedes', 'Guerra, Susana']",Viruses,,,True
7ba9c9ed2f4e80906b5fcdcd69b3537b3309f5e2,PMC,Mechanisms of Cellular Membrane Reorganization to Support Hepatitis C Virus Replication,http://dx.doi.org/10.3390/v8050142,PMC4885097,27213428,CC BY,"Like all positive-sense RNA viruses, hepatitis C virus (HCV) induces host membrane alterations for its replication termed the membranous web (MW). Assembling replication factors at a membranous structure might facilitate the processes necessary for genome replication and packaging and shield viral components from host innate immune defenses. The biogenesis of the HCV MW is a complex process involving a concerted effort of HCV nonstructural proteins with a growing list of host factors. Although a comprehensive understanding of MW formation is still missing, a number of important viral and host determinants have been identified. This review will summarize the recent studies that have led to our current knowledge of the role of viral and host factors in the biogenesis of the MWs and discuss how HCV uses this specialized membrane structure for its replication.",2016 May 20,"['Wang, Hongliang', 'Tai, Andrew W.']",Viruses,,,True
2d1d0fbb79973ccbe29af6ae067aa91d05599a4f,PMC,HACE1 Negatively Regulates Virus-Triggered Type I IFN Signaling by Impeding the Formation of the MAVS-TRAF3 Complex,http://dx.doi.org/10.3390/v8050146,PMC4885101,27213432,CC BY,"During virus infection, the cascade signaling pathway that leads to the production of proinflammatory cytokines is controlled at multiple levels to avoid detrimental overreaction. HACE1 has been characterized as an important tumor suppressor. Here, we identified HACE1 as an important negative regulator of virus-triggered type I IFN signaling. Overexpression of HACE1 inhibited Sendai virus- or poly (I:C)-induced signaling and resulted in reduced IFNB1 production and enhanced virus replication. Knockdown of HACE1 expression exhibited the opposite effects. Ubiquitin E3 ligase activity of the dead mutant HACE1/C876A had a comparable inhibitory function as WT HACE1, suggesting that the suppressive function of HACE1 on virus-induced signaling is independent of its E3 ligase activity. Further study indicated that HACE1 acted downstream of MAVS and upstream of TBK1. Mechanistic studies showed that HACE1 exerts its inhibitory role on virus-induced signaling by disrupting the MAVS-TRAF3 complex. Therefore, we uncovered a novel function of HACE1 in innate immunity regulation.",2016 May 21,"['Mao, He-Ting', 'Wang, Yan', 'Cai, Juan', 'Meng, Jun-Ling', 'Zhou, Yu', 'Pan, Yu', 'Qian, Xiao-Ping', 'Zhang, Yu', 'Zhang, Jun']",Viruses,,,True
740bbfc884c50507fbf78e9424da319a49c48af0,PMC,Para-Phenylenediamine Induces Apoptotic Death of Melanoma Cells and Reduces Melanoma Tumour Growth in Mice,http://dx.doi.org/10.1155/2016/3137010,PMC4886052,27293892,CC BY,"Melanoma is one of the most aggressive forms of cancer, usually resistant to standard chemotherapeutics. Despite a huge number of clinical trials, any success to find a chemotherapeutic agent that can effectively destroy melanoma is yet to be achieved. Para-phenylenediamine (p-PD) in the hair dyes is reported to purely serve as an external dyeing agent. Very little is known about whether p-PD has any effect on the melanin producing cells. We have demonstrated p-PD mediated apoptotic death of both human and mouse melanoma cells in vitro. Mouse melanoma tumour growth was also arrested by the apoptotic activity of intraperitoneal administration of p-PD with almost no side effects. This apoptosis is shown to occur primarily via loss of mitochondrial membrane potential (MMP), generation of reactive oxygen species (ROS), and caspase 8 activation. p-PD mediated apoptosis was also confirmed by the increase in sub-G0/G1 cell number. Thus, our experimental observation suggests that p-PD can be a potential less expensive candidate to be developed as a chemotherapeutic agent for melanoma.",2016 May 17,"['Bhowmick, Debajit', 'Bhar, Kaushik', 'Mallick, Sanjaya K.', 'Das, Subhadip', 'Chatterjee, Nabanita', 'Sarkar, Tuhin Subhra', 'Chakrabarti, Rajarshi', 'Das Saha, Krishna', 'Siddhanta, Anirban']",Biochem Res Int,,,True
75882d6856d4243248aa32fe119153efeb0dbe12,PMC,Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression,http://dx.doi.org/10.1128/JVI.02557-15,PMC4886784,27009955,CC BY,"Inflammation may be maladaptive to the control of viral infection when it impairs interferon (IFN) responses, enhancing viral replication and spread. Dysregulated immunity as a result of inappropriate innate inflammatory responses is a hallmark of chronic viral infections such as, hepatitis B virus and hepatitis C virus (HCV). Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Human hepatoma cells and primary murine hepatocytes were treated with TNF-α/LPS/IL-6/IL-10 and USP18, phosphorylated (p)-STAT1 and myxovirus (influenza virus) resistance 1 (Mx1) expression was determined. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. Liver inflammation was induced in vivo using a murine model of hepatic ischemia/reperfusion injury. Hepatic ischemia/reperfusion injury led to an induction of USP18 expression in liver tissue and promotion of lymphocytic choriomeningitis replication. These data demonstrate that certain inflammatory stimuli (TNF-α and LPS) but not others (IL-6 and IL-10) target USP18 expression and thus inhibit IFN signaling. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with USP18 representing a potential target for intervention in various inflammatory states. IMPORTANCE Inflammation may prevent the control of viral infection when it impairs the innate immune response, enhancing viral replication and spread. Blunted immunity as a result of inappropriate innate inflammatory responses is a common characteristic of chronic viral infections. Previous studies have shown that expression of certain interferon-stimulated genes is upregulated in chronic HCV infection, leading to impaired hepatocyte responses. In this study, we show that multiple inflammatory stimuli can modulate interferon stimulated gene expression and thus inhibit hepatocyte interferon signaling via USP18 induction. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with the induction of USP18 representing a potential target for intervention in various inflammatory states.",2016 May 27,"['MacParland, Sonya A.', 'Ma, Xue-Zhong', 'Chen, Limin', 'Khattar, Ramzi', 'Cherepanov, Vera', 'Selzner, Markus', 'Feld, Jordan J.', 'Selzner, Nazia', 'McGilvray, Ian D.']",J Virol,,,True
dc7de10933e811946c548cca7b1f3dbe61161d13,PMC,Evolution-guided functional analyses reveal diverse antiviral specificities encoded by IFIT1 genes in mammals,http://dx.doi.org/10.7554/eLife.14228,PMC4887208,27240734,CC BY,"IFIT (interferon-induced with tetratricopeptide repeats) proteins are critical mediators of mammalian innate antiviral immunity. Mouse IFIT1 selectively inhibits viruses that lack 2'O-methylation of their mRNA 5' caps. Surprisingly, human IFIT1 does not share this antiviral specificity. Here, we resolve this discrepancy by demonstrating that human and mouse IFIT1 have evolved distinct functions using a combination of evolutionary, genetic and virological analyses. First, we show that human IFIT1 and mouse IFIT1 (renamed IFIT1B) are not orthologs, but are paralogs that diverged >100 mya. Second, using a yeast genetic assay, we show that IFIT1 and IFIT1B proteins differ in their ability to be suppressed by a cap 2'O-methyltransferase. Finally, we demonstrate that IFIT1 and IFIT1B have divergent antiviral specificities, including the discovery that only IFIT1 proteins inhibit a virus encoding a cap 2'O-methyltransferase. These functional data, combined with widespread turnover of mammalian IFIT genes, reveal dramatic species-specific differences in IFIT-mediated antiviral repertoires. DOI: http://dx.doi.org/10.7554/eLife.14228.001",,"['Daugherty, Matthew D', 'Schaller, Aaron M', 'Geballe, Adam P', 'Malik, Harmit S']",eLife.; 5:e14228,,,True
4ea6973e872fb9116a21c6539d2aba2ea5c1337c,PMC,Protein Kinase C-δ Mediates Shedding of Angiotensin-Converting Enzyme 2 from Proximal Tubular Cells,http://dx.doi.org/10.3389/fphar.2016.00146,PMC4887483,27313531,CC BY,"Angiotensin-converting enzyme 2 (ACE2) degrades angiotensin (Ang) II to Ang-(1–7), and protects against diabetic renal injury. Soluble ACE2 fragments are shed from the proximal tubule, and appear at high levels in the urine with diabetes. High glucose-induced shedding of ACE2 from proximal tubular cells is mediated by the enzyme “a disintegrin and metalloproteinase-17″ (ADAM17). Here, we investigated the mechanism for constitutive shedding of ACE2. Mouse proximal tubular cells were cultured and ACE2 shedding into the media was assessed by enzyme activity assay and immunoblot analysis. Cells were incubated with pharmacologic inhibitors, or transfected with silencing (si) RNA. Incubation of proximal tubular cells with increasing concentrations of D-glucose stimulated ACE2 shedding, which peaked at 16 mM, while L-glucose (osmotic control) had no effect on shedding. In cells maintained in 7.8 mM D-glucose, ACE2 shedding was significantly inhibited by the pan-protein kinase C (PKC) competitive inhibitor sotrastaurin, but not by an inhibitor of ADAM17. Incubation of cells with the PKC-α and -β1-specific inhibitor Go6976, the PKC β1 and β2-specific inhibitor ruboxistaurin, inhibitors of matrix metalloproteinases-2,-8, and -9, or an inhibitor of ADAM10 (GI250423X) had no effect on basal ACE2 shedding. By contrast, the PKC-δ inhibitor rottlerin significantly inhibited both constitutive and high glucose-induced ACE2 shedding. Transfection of cells with siRNA directed against PKC-δ reduced ACE2 shedding by 20%, while knockdown of PKC-ε was without effect. These results indicate that constitutive shedding of ACE2 from proximal tubular cells is mediated by PKC-δ, which is also linked to high glucose-induced shedding. Targeting PKC-δ may preserve membrane-bound ACE2 in proximal tubule in disease states and diminish Ang II-stimulated adverse signaling.",2016 Jun 1,"['Xiao, Fengxia', 'Zimpelmann, Joseph', 'Burger, Dylan', 'Kennedy, Christopher', 'Hébert, Richard L.', 'Burns, Kevin D.']",Front Pharmacol,,,True
364f3e45183f362e8398724c29d3b010436ce375,PMC,Biomarkers in Pediatric ARDS: Future Directions,http://dx.doi.org/10.3389/fped.2016.00055,PMC4887507,27313995,CC BY,"Acute respiratory distress syndrome (ARDS) is common among mechanically ventilated children and accompanies up to 30% of all pediatric intensive care unit deaths. Though ARDS diagnosis is based on clinical criteria, biological markers of acute lung damage have been extensively studied in adults and children. Biomarkers of inflammation, alveolar epithelial and capillary endothelial disruption, disordered coagulation, and associated derangements measured in the circulation and other body fluids, such as bronchoalveolar lavage, have improved our understanding of pathobiology of ARDS. The biochemical signature of ARDS has been increasingly well described in adult populations, and this has led to the identification of molecular phenotypes to augment clinical classifications. However, there is a paucity of data from pediatric ARDS (pARDS) patients. Biomarkers and molecular phenotypes have the potential to identify patients at high risk of poor outcomes, and perhaps inform the development of targeted therapies for specific groups of patients. Additionally, because of the lower incidence of and mortality from ARDS in pediatric patients relative to adults and lack of robust clinical predictors of outcome, there is an ongoing interest in biological markers as surrogate outcome measures. The recent definition of pARDS provides additional impetus for the measurement of established and novel biomarkers in future pediatric studies in order to further characterize this disease process. This chapter will review the currently available literature and discuss potential future directions for investigation into biomarkers in ARDS among children.",2016 Jun 1,"['Orwoll, Benjamin E.', 'Sapru, Anil']",Front Pediatr,,,True
c5df32e01e9583e1b4430418e8f8f58c8a85021c,PMC,Establishment and application of a real-time loop-mediated isothermal amplification system for the detection of CYP2C19 polymorphisms,http://dx.doi.org/10.1038/srep26533,PMC4887897,27246657,CC BY,"Single-nucleotide polymorphisms (SNPs) represent the most widespread type of genetic variation (approximately 90%) in the human genome, and the demand to overcome such variation has received more attention now than ever before. The capacity to rapidly assess SNPs that correlate with disease predisposition, drug efficacy and drug toxicity is a key step for the development of personalized medicine. In this work, a rapid one-step SNP detection method, real-time loop-mediated isothermal amplification (RT-LAMP), was first applied for CYP2C19 polymorphisms testing. The optimized method was established with specifically designed primers for target amplification by real-time detection in approximately 30 min under isothermal conditions. RT-LAMP amplified few copies of template to produce significant amounts of product and quantitatively detected human DNA with compatible specificity and sensitivity. The success in the establishment of this RT-LAMP protocol for CYP2C19 polymorphism testing is significant for the extension of this technique for the detection of other SNPs, which will further facilitate the development of personalized medicine.",2016 Jun 1,"['Zhang, Chao', 'Yao, Yao', 'Zhu, Juan-Li', 'Zhang, Si-Nong', 'Zhang, Shan-Shan', 'Wei, Hua', 'Hui, Wen-Li', 'Cui, Ya-Li']",Sci Rep,,,True
9363688452b649c407692622c30b4b5bc346c87e,PMC,Establishment and application of a real-time loop-mediated isothermal amplification system for the detection of CYP2C19 polymorphisms,http://dx.doi.org/10.1038/srep26533,PMC4887897,27246657,CC BY,"Single-nucleotide polymorphisms (SNPs) represent the most widespread type of genetic variation (approximately 90%) in the human genome, and the demand to overcome such variation has received more attention now than ever before. The capacity to rapidly assess SNPs that correlate with disease predisposition, drug efficacy and drug toxicity is a key step for the development of personalized medicine. In this work, a rapid one-step SNP detection method, real-time loop-mediated isothermal amplification (RT-LAMP), was first applied for CYP2C19 polymorphisms testing. The optimized method was established with specifically designed primers for target amplification by real-time detection in approximately 30 min under isothermal conditions. RT-LAMP amplified few copies of template to produce significant amounts of product and quantitatively detected human DNA with compatible specificity and sensitivity. The success in the establishment of this RT-LAMP protocol for CYP2C19 polymorphism testing is significant for the extension of this technique for the detection of other SNPs, which will further facilitate the development of personalized medicine.",2016 Jun 1,"['Zhang, Chao', 'Yao, Yao', 'Zhu, Juan-Li', 'Zhang, Si-Nong', 'Zhang, Shan-Shan', 'Wei, Hua', 'Hui, Wen-Li', 'Cui, Ya-Li']",Sci Rep,,,False
92ced556ed66213053dfc7abfa35deb9c1f8ef8e,PMC,"Is the global health community prepared for future pandemics? A need for solidarity, resources and strong governance",http://dx.doi.org/10.15252/emmm.201606337,PMC4888848,27137494,CC BY,"In the wake of recent outbreaks of Zika, Ebola and the MERS‐CoV viruses, many are asking: how prepared is the global public health community to deal with future emerging pandemics? Collective action at national, regional and global levels is the best way forward. [Image: see text]",2016 Jun 21,"Pang, Tikki",EMBO Mol Med,,,True
91c146beba875fde88ed4e4770cfb6325ad2f038,PMC,HTCC: Broad Range Inhibitor of Coronavirus Entry,http://dx.doi.org/10.1371/journal.pone.0156552,PMC4889042,27249425,CC BY,"To date, six human coronaviruses have been known, all of which are associated with respiratory infections in humans. With the exception of the highly pathogenic SARS and MERS coronaviruses, human coronaviruses (HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoV-HKU1) circulate worldwide and typically cause the common cold. In most cases, infection with these viruses does not lead to severe disease, although acute infections in infants, the elderly, and immunocompromised patients may progress to severe disease requiring hospitalization. Importantly, no drugs against human coronaviruses exist, and only supportive therapy is available. Previously, we proposed the cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and its hydrophobically-modified derivative (HM-HTCC) as potent inhibitors of the coronavirus HCoV-NL63. Here, we show that HTCC inhibits interaction of a virus with its receptor and thus blocks the entry. Further, we demonstrate that HTCC polymers with different degrees of substitution act as effective inhibitors of all low-pathogenic human coronaviruses.",2016 Jun 1,"['Milewska, Aleksandra', 'Kaminski, Kamil', 'Ciejka, Justyna', 'Kosowicz, Katarzyna', 'Zeglen, Slawomir', 'Wojarski, Jacek', 'Nowakowska, Maria', 'Szczubiałka, Krzysztof', 'Pyrc, Krzysztof']",PLoS One,,,True
dbf76534e0b330bb0f155296e251c1e7031c90c0,PMC,The Respiratory Protection Effectiveness Clinical Trial (ResPECT): a cluster-randomized comparison of respirator and medical mask effectiveness against respiratory infections in healthcare personnel,http://dx.doi.org/10.1186/s12879-016-1494-2,PMC4890247,27255755,CC BY,"BACKGROUND: Although N95 filtering facepiece respirators and medical masks are commonly used for protection against respiratory infections in healthcare settings, more clinical evidence is needed to understand the optimal settings and exposure circumstances for healthcare personnel to use these devices. A lack of clinically germane research has led to equivocal, and occasionally conflicting, healthcare respiratory protection recommendations from public health organizations, professional societies, and experts. METHODS: The Respiratory Protection Effectiveness Clinical Trial (ResPECT) is a prospective comparison of respiratory protective equipment to be conducted at multiple U.S. study sites. Healthcare personnel who work in outpatient settings will be cluster-randomized to wear N95 respirators or medical masks for protection against infections during respiratory virus season. Outcome measures will include laboratory-confirmed viral respiratory infections, acute respiratory illness, and influenza-like illness. Participant exposures to patients, coworkers, and others with symptoms and signs of respiratory infection, both within and beyond the workplace, will be recorded in daily diaries. Adherence to study protocols will be monitored by the study team. DISCUSSION: ResPECT is designed to better understand the extent to which N95s and MMs reduce clinical illness among healthcare personnel. A fully successful study would produce clinically relevant results that help clinician-leaders make reasoned decisions about protection of healthcare personnel against occupationally acquired respiratory infections and prevention of spread within healthcare systems. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov, number NCT01249625 (11/29/2010).",2016 Jun 2,"['Radonovich, Lewis J.', 'Bessesen, Mary T.', 'Cummings, Derek A.', 'Eagan, Aaron', 'Gaydos, Charlotte', 'Gibert, Cynthia', 'Gorse, Geoffrey J.', 'Nyquist, Ann-Christine', 'Reich, Nicholas G.', 'Rodrigues-Barradas, Maria', 'Savor-Price, Connie', 'Shaffer, Ronald E.', 'Simberkoff, Michael S.', 'Perl, Trish M.']",BMC Infect Dis,,,True
a85a6d90b479fd8547830827ec8898750794cdf3,PMC,Autophagy: New Questions from Recent Answers,http://dx.doi.org/10.5402/2012/738718,PMC4890908,27335669,CC BY,"Macroautophagy (hereafter autophagy) is currently one of the areas of medical life sciences attracting a great interest because of its pathological implications and therapy potentials. The discovery of the autophagy-related genes (ATGs) has been the key event in this research field because their study has led to the acquisition of new knowledge about the mechanism of this transport pathway. In addition, the investigation of these genes in numerous model systems has revealed the central role that autophagy plays in maintaining the cell homeostasis. This process carries out numerous physiological functions, some of which were unpredicted and thus surprising. Here, we will review some of the questions about the mechanism and function of autophagy that still remain unanswered, and new ones that have emerged from the recent discoveries.",2012 Dec 30,"Reggiori, Fulvio",ISRN Mol Biol,,,True
e447d139f1d046120a293f1219944e82c77bc829,PMC,"Oblongifolin M, an active compound isolated from a Chinese medical herb Garcinia oblongifolia, potently inhibits enterovirus 71 reproduction through downregulation of ERp57",http://dx.doi.org/10.18632/oncotarget.7122,PMC4891005,26848777,CC BY,"There is no effective drug to treat EV71 infection yet. Traditional Chinese herbs are great resources for novel antiviral compounds. Here we showed that Oblongifolin M (OM), an active compound isolated from Garcinia oblongifolia, potently inhibited EV71 infection in a dose dependent manner. To identify its potential effectors in the host cells, we successfully identified 18 proteins from 52 differentially expressed spots by comparative proteomics studies. Further studies showed that knockdown of ERp57 inhibited viral replication through downregulating viral IRES (internal ribosome entry site) activities, whereas ectopic expression of ERp57 increased IRES activity and partly rescued the inhibitory effects of OM on viral replication. We demonstrated that OM is an effective antiviral agent; and that ERp57 is one of its cellular effectors against EV71 infection.",2016 Feb 1,"['Wang, Mengjie', 'Dong, Qi', 'Wang, Hua', 'He, Yaqing', 'Chen, Ying', 'Zhang, Hong', 'Wu, Rong', 'Chen, Xinchun', 'Zhou, Boping', 'He, Jason', 'Kung, Hsiang-Fu', 'Huang, Canhua', 'Wei, Yuquan', 'Huang, Jian-dong', 'Xu, Hongxi', 'He, Ming-Liang']",Oncotarget,,,True
8fae4d1f513f03412a39c288a957fe5573c48b41,PMC,"Oblongifolin M, an active compound isolated from a Chinese medical herb Garcinia oblongifolia, potently inhibits enterovirus 71 reproduction through downregulation of ERp57",http://dx.doi.org/10.18632/oncotarget.7122,PMC4891005,26848777,CC BY,"There is no effective drug to treat EV71 infection yet. Traditional Chinese herbs are great resources for novel antiviral compounds. Here we showed that Oblongifolin M (OM), an active compound isolated from Garcinia oblongifolia, potently inhibited EV71 infection in a dose dependent manner. To identify its potential effectors in the host cells, we successfully identified 18 proteins from 52 differentially expressed spots by comparative proteomics studies. Further studies showed that knockdown of ERp57 inhibited viral replication through downregulating viral IRES (internal ribosome entry site) activities, whereas ectopic expression of ERp57 increased IRES activity and partly rescued the inhibitory effects of OM on viral replication. We demonstrated that OM is an effective antiviral agent; and that ERp57 is one of its cellular effectors against EV71 infection.",2016 Feb 1,"['Wang, Mengjie', 'Dong, Qi', 'Wang, Hua', 'He, Yaqing', 'Chen, Ying', 'Zhang, Hong', 'Wu, Rong', 'Chen, Xinchun', 'Zhou, Boping', 'He, Jason', 'Kung, Hsiang-Fu', 'Huang, Canhua', 'Wei, Yuquan', 'Huang, Jian-dong', 'Xu, Hongxi', 'He, Ming-Liang']",Oncotarget,,,False
ada981b0b99f2468f331107ff419b9aea9c9175e,PMC,Extensive coronavirus-induced membrane rearrangements are not a determinant of pathogenicity,http://dx.doi.org/10.1038/srep27126,PMC4891661,27255716,CC BY,"Positive-strand RNA (+RNA) viruses rearrange cellular membranes during replication, possibly in order to concentrate and arrange viral replication machinery for efficient viral RNA synthesis. Our previous work showed that in addition to the conserved coronavirus double membrane vesicles (DMVs), Beau-R, an apathogenic strain of avian Gammacoronavirus infectious bronchitis virus (IBV), induces regions of ER that are zippered together and tethered open-necked double membrane spherules that resemble replication organelles induced by other +RNA viruses. Here we compared structures induced by Beau-R with the pathogenic lab strain M41 to determine whether membrane rearrangements are strain dependent. Interestingly, M41 was found to have a low spherule phenotype. We then compared a panel of pathogenic, mild and attenuated IBV strains in ex vivo tracheal organ culture (TOC). Although the low spherule phenotype of M41 was conserved in TOCs, each of the other tested IBV strains produced DMVs, zippered ER and spherules. Furthermore, there was a significant correlation for the presence of DMVs with spherules, suggesting that these structures are spatially and temporally linked. Our data indicate that virus induced membrane rearrangements are fundamentally linked to the viral replicative machinery. However, coronavirus replicative apparatus clearly has the plasticity to function in different structural contexts.",2016 Jun 3,"['Maier, Helena J.', 'Neuman, Benjamin W.', 'Bickerton, Erica', 'Keep, Sarah M.', 'Alrashedi, Hasan', 'Hall, Ross', 'Britton, Paul']",Sci Rep,,,True
3f23cb13bcb298f25433f191853049d2fa904565,PMC,Extensive coronavirus-induced membrane rearrangements are not a determinant of pathogenicity,http://dx.doi.org/10.1038/srep27126,PMC4891661,27255716,CC BY,"Positive-strand RNA (+RNA) viruses rearrange cellular membranes during replication, possibly in order to concentrate and arrange viral replication machinery for efficient viral RNA synthesis. Our previous work showed that in addition to the conserved coronavirus double membrane vesicles (DMVs), Beau-R, an apathogenic strain of avian Gammacoronavirus infectious bronchitis virus (IBV), induces regions of ER that are zippered together and tethered open-necked double membrane spherules that resemble replication organelles induced by other +RNA viruses. Here we compared structures induced by Beau-R with the pathogenic lab strain M41 to determine whether membrane rearrangements are strain dependent. Interestingly, M41 was found to have a low spherule phenotype. We then compared a panel of pathogenic, mild and attenuated IBV strains in ex vivo tracheal organ culture (TOC). Although the low spherule phenotype of M41 was conserved in TOCs, each of the other tested IBV strains produced DMVs, zippered ER and spherules. Furthermore, there was a significant correlation for the presence of DMVs with spherules, suggesting that these structures are spatially and temporally linked. Our data indicate that virus induced membrane rearrangements are fundamentally linked to the viral replicative machinery. However, coronavirus replicative apparatus clearly has the plasticity to function in different structural contexts.",2016 Jun 3,"['Maier, Helena J.', 'Neuman, Benjamin W.', 'Bickerton, Erica', 'Keep, Sarah M.', 'Alrashedi, Hasan', 'Hall, Ross', 'Britton, Paul']",Sci Rep,,,False
97699e1e790ab279013460ac4478cc6b9832d2e1,PMC,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) origin and animal reservoir,http://dx.doi.org/10.1186/s12985-016-0544-0,PMC4891877,27255185,CC BY,"Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans. Though not confirmed yet, multiple surveillance and phylogenetic studies suggest a bat origin. The disease is heavily endemic in dromedary camel populations of East Africa and the Middle East. It is unclear as to when the virus was introduced to dromedary camels, but data from studies that investigated stored dromedary camel sera and geographical distribution of involved dromedary camel populations suggested that the virus was present in dromedary camels several decades ago. Though bats and alpacas can serve as potential reservoirs for MERS-CoV, dromedary camels seem to be the only animal host responsible for the spill over human infections.",2016 Jun 3,"['Mohd, Hamzah A.', 'Al-Tawfiq, Jaffar A.', 'Memish, Ziad A.']",Virol J,,,True
945fd47a82b49774675d732d27f6b806c0e6aeb1,PMC,Nonhuman Primate IFITM Proteins Are Potent Inhibitors of HIV and SIV,http://dx.doi.org/10.1371/journal.pone.0156739,PMC4892622,27257969,CC BY,"Interferon-induced transmembrane (IFITM) proteins are potent antiviral factors shown to restrict the infection of many enveloped viruses, including HIV. Here we report cloning and characterization of a panel of nonhuman primate IFITMs. We show that, similar to human IFITM, nonhuman primate IFITM proteins inhibit HIV and other primate lentiviruses. While some nonhuman primate IFITM proteins are more potent than human counterparts to inhibit HIV-1, they are generally not effective against HIV-2 similar to that of human IFITMs. Notably, depending on SIV strains and also IFITM species tested, nonhuman primate IFITM proteins exhibit distinct activities against SIVs; no correlation was found to support the notion that IFITM proteins are most active in non-natural primate hosts. Consistent with our recent findings for human IFITMs, nonhuman primate IFITM proteins interact with HIV-1 Env and strongly act in viral producer cells to impair viral infectivity and block cell-to-cell transmission. Accordingly, knockdown of primate IFITM3 increases HIV-1 replication in nohuman primate cells. Interestingly, analysis of DNA sequences of human and nonhuman primate IFITMs suggest that IFITM proteins have been undergoing purifying selection, rather than positive selection typical for cellular restriction factors. Overall, our study reveals some new and unexpected features of IFITMs in restricting primate lentiviruses, which enhances our understanding of virus-host interaction and AIDS pathogenesis.",2016 Jun 3,"['Wilkins, Jordan', 'Zheng, Yi-Min', 'Yu, Jingyou', 'Liang, Chen', 'Liu, Shan-Lu']",PLoS One,,,True
2e28d846c5181c13e9ff54ef725fb009dd966b47,PMC,Severe maternal morbidity due to respiratory disease and impact of 2009 H1N1 influenza A pandemic in Brazil: results from a national multicenter cross-sectional study,http://dx.doi.org/10.1186/s12879-016-1525-z,PMC4894555,27207244,CC BY,"BACKGROUND: The aim of this study was to assess the burden of respiratory disease, considering the influenza A pandemic season (H1N1pdm09), within the Brazilian Network for Surveillance of Severe Maternal Morbidity, and factors associated with worse maternal outcome. METHODS: A multicenter cross-sectional study, involving 27 referral maternity hospitals in five Brazilian regions. Cases were identified in a prospective surveillance by using the WHO standardized criteria for potentially life-threatening conditions (PLTC) and maternal near miss (MNM). Women with severe complications from respiratory disease identified as suspected or confirmed cases of H1N1 influenza or respiratory failure were compared to those with other causes of severe morbidity. A review of suspected H1N1 influenza cases classified women as non-tested, tested positive and tested negative, comparing their outcomes. Factors associated with severe maternal outcome (SMO = MNM + MD) were assessed in both groups, in comparison to PLTC, using PR and 95 % CI adjusted for design effect of cluster sampling. RESULTS: Among 9555 cases of severe maternal morbidity, 485 (5 %) had respiratory disease. Respiratory disease occurred in one-quarter of MNM cases and two-thirds of MD. H1N1 virus was suspected in 206 cases with respiratory illness. Around 60 % of these women were tested, yielding 49 confirmed cases. Confirmed H1N1 influenza cases had worse adverse outcomes (MNM:MD ratio < 1 (0.9:1), compared to 12:1 in cases due to other causes), and a mortality index > 50 %, in comparison to 7.4 % in other causes of severe maternal morbidity. Delay in medical care was associated with SMO in all cases considered, with a two-fold increased risk among respiratory disease patients. Perinatal outcome was worse in cases complicated by respiratory disease, with increased prematurity, stillbirth, low birth weight and Apgar score < 7. CONCLUSIONS: Respiratory disease, especially considering the influenza season, is a very severe cause of maternal near miss and death. Increased awareness about this condition, preventive vaccination during pregnancy, early diagnosis and treatment are required to improve maternal health.",2016 May 21,"['Pfitscher, L. C.', 'Cecatti, J. G.', 'Pacagnella, R. C.', 'Haddad, S. M.', 'Parpinelli, M. A.', 'Souza, J. P.', 'Quintana, S. M.', 'Surita, F. G.', 'Sousa, M. H.', 'Costa, M. L.', None]",BMC Infect Dis,,,True
b8a27d9cc6b79620fefffaf23778c2d799248682,PMC,Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data,http://dx.doi.org/10.1371/journal.pcbi.1004876,PMC4894584,27271698,CC BY,"The estimation of disease prevalence in online search engine data (e.g., Google Flu Trends (GFT)) has received a considerable amount of scholarly and public attention in recent years. While the utility of search engine data for disease surveillance has been demonstrated, the scientific community still seeks ways to identify and reduce biases that are embedded in search engine data. The primary goal of this study is to explore new ways of improving the accuracy of disease prevalence estimations by combining traditional disease data with search engine data. A novel method, Biased Sentinel Hospital-based Area Disease Estimation (B-SHADE), is introduced to reduce search engine data bias from a geographical perspective. To monitor search trends on Hand, Foot and Mouth Disease (HFMD) in Guangdong Province, China, we tested our approach by selecting 11 keywords from the Baidu index platform, a Chinese big data analyst similar to GFT. The correlation between the number of real cases and the composite index was 0.8. After decomposing the composite index at the city level, we found that only 10 cities presented a correlation of close to 0.8 or higher. These cities were found to be more stable with respect to search volume, and they were selected as sample cities in order to estimate the search volume of the entire province. After the estimation, the correlation improved from 0.8 to 0.864. After fitting the revised search volume with historical cases, the mean absolute error was 11.19% lower than it was when the original search volume and historical cases were combined. To our knowledge, this is the first study to reduce search engine data bias levels through the use of rigorous spatial sampling strategies.",2016 Jun 6,"['Huang, Da-Cang', 'Wang, Jin-Feng', 'Huang, Ji-Xia', 'Sui, Daniel Z.', 'Zhang, Hong-Yan', 'Hu, Mao-Gui', 'Xu, Cheng-Dong']",PLoS Comput Biol,,,True
9bb4db31c5490bc2f6f5e3c54d3a2ed7ce69048a,PMC,Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data,http://dx.doi.org/10.1371/journal.pcbi.1004876,PMC4894584,27271698,CC BY,"The estimation of disease prevalence in online search engine data (e.g., Google Flu Trends (GFT)) has received a considerable amount of scholarly and public attention in recent years. While the utility of search engine data for disease surveillance has been demonstrated, the scientific community still seeks ways to identify and reduce biases that are embedded in search engine data. The primary goal of this study is to explore new ways of improving the accuracy of disease prevalence estimations by combining traditional disease data with search engine data. A novel method, Biased Sentinel Hospital-based Area Disease Estimation (B-SHADE), is introduced to reduce search engine data bias from a geographical perspective. To monitor search trends on Hand, Foot and Mouth Disease (HFMD) in Guangdong Province, China, we tested our approach by selecting 11 keywords from the Baidu index platform, a Chinese big data analyst similar to GFT. The correlation between the number of real cases and the composite index was 0.8. After decomposing the composite index at the city level, we found that only 10 cities presented a correlation of close to 0.8 or higher. These cities were found to be more stable with respect to search volume, and they were selected as sample cities in order to estimate the search volume of the entire province. After the estimation, the correlation improved from 0.8 to 0.864. After fitting the revised search volume with historical cases, the mean absolute error was 11.19% lower than it was when the original search volume and historical cases were combined. To our knowledge, this is the first study to reduce search engine data bias levels through the use of rigorous spatial sampling strategies.",2016 Jun 6,"['Huang, Da-Cang', 'Wang, Jin-Feng', 'Huang, Ji-Xia', 'Sui, Daniel Z.', 'Zhang, Hong-Yan', 'Hu, Mao-Gui', 'Xu, Cheng-Dong']",PLoS Comput Biol,,,True
6660c114ae3ea21b9a1551e9253d767d5b7ae9f7,PMC,Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data,http://dx.doi.org/10.1371/journal.pcbi.1004876,PMC4894584,27271698,CC BY,"The estimation of disease prevalence in online search engine data (e.g., Google Flu Trends (GFT)) has received a considerable amount of scholarly and public attention in recent years. While the utility of search engine data for disease surveillance has been demonstrated, the scientific community still seeks ways to identify and reduce biases that are embedded in search engine data. The primary goal of this study is to explore new ways of improving the accuracy of disease prevalence estimations by combining traditional disease data with search engine data. A novel method, Biased Sentinel Hospital-based Area Disease Estimation (B-SHADE), is introduced to reduce search engine data bias from a geographical perspective. To monitor search trends on Hand, Foot and Mouth Disease (HFMD) in Guangdong Province, China, we tested our approach by selecting 11 keywords from the Baidu index platform, a Chinese big data analyst similar to GFT. The correlation between the number of real cases and the composite index was 0.8. After decomposing the composite index at the city level, we found that only 10 cities presented a correlation of close to 0.8 or higher. These cities were found to be more stable with respect to search volume, and they were selected as sample cities in order to estimate the search volume of the entire province. After the estimation, the correlation improved from 0.8 to 0.864. After fitting the revised search volume with historical cases, the mean absolute error was 11.19% lower than it was when the original search volume and historical cases were combined. To our knowledge, this is the first study to reduce search engine data bias levels through the use of rigorous spatial sampling strategies.",2016 Jun 6,"['Huang, Da-Cang', 'Wang, Jin-Feng', 'Huang, Ji-Xia', 'Sui, Daniel Z.', 'Zhang, Hong-Yan', 'Hu, Mao-Gui', 'Xu, Cheng-Dong']",PLoS Comput Biol,,,False
c43ec4dfe55ad2ad03d889319eff02fbbec582f8,PMC,Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data,http://dx.doi.org/10.1371/journal.pcbi.1004876,PMC4894584,27271698,CC BY,"The estimation of disease prevalence in online search engine data (e.g., Google Flu Trends (GFT)) has received a considerable amount of scholarly and public attention in recent years. While the utility of search engine data for disease surveillance has been demonstrated, the scientific community still seeks ways to identify and reduce biases that are embedded in search engine data. The primary goal of this study is to explore new ways of improving the accuracy of disease prevalence estimations by combining traditional disease data with search engine data. A novel method, Biased Sentinel Hospital-based Area Disease Estimation (B-SHADE), is introduced to reduce search engine data bias from a geographical perspective. To monitor search trends on Hand, Foot and Mouth Disease (HFMD) in Guangdong Province, China, we tested our approach by selecting 11 keywords from the Baidu index platform, a Chinese big data analyst similar to GFT. The correlation between the number of real cases and the composite index was 0.8. After decomposing the composite index at the city level, we found that only 10 cities presented a correlation of close to 0.8 or higher. These cities were found to be more stable with respect to search volume, and they were selected as sample cities in order to estimate the search volume of the entire province. After the estimation, the correlation improved from 0.8 to 0.864. After fitting the revised search volume with historical cases, the mean absolute error was 11.19% lower than it was when the original search volume and historical cases were combined. To our knowledge, this is the first study to reduce search engine data bias levels through the use of rigorous spatial sampling strategies.",2016 Jun 6,"['Huang, Da-Cang', 'Wang, Jin-Feng', 'Huang, Ji-Xia', 'Sui, Daniel Z.', 'Zhang, Hong-Yan', 'Hu, Mao-Gui', 'Xu, Cheng-Dong']",PLoS Comput Biol,,,False
8ca4fb44ca22975a061b3cc8a164f11466c4906d,PMC,Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data,http://dx.doi.org/10.1371/journal.pcbi.1004876,PMC4894584,27271698,CC BY,"The estimation of disease prevalence in online search engine data (e.g., Google Flu Trends (GFT)) has received a considerable amount of scholarly and public attention in recent years. While the utility of search engine data for disease surveillance has been demonstrated, the scientific community still seeks ways to identify and reduce biases that are embedded in search engine data. The primary goal of this study is to explore new ways of improving the accuracy of disease prevalence estimations by combining traditional disease data with search engine data. A novel method, Biased Sentinel Hospital-based Area Disease Estimation (B-SHADE), is introduced to reduce search engine data bias from a geographical perspective. To monitor search trends on Hand, Foot and Mouth Disease (HFMD) in Guangdong Province, China, we tested our approach by selecting 11 keywords from the Baidu index platform, a Chinese big data analyst similar to GFT. The correlation between the number of real cases and the composite index was 0.8. After decomposing the composite index at the city level, we found that only 10 cities presented a correlation of close to 0.8 or higher. These cities were found to be more stable with respect to search volume, and they were selected as sample cities in order to estimate the search volume of the entire province. After the estimation, the correlation improved from 0.8 to 0.864. After fitting the revised search volume with historical cases, the mean absolute error was 11.19% lower than it was when the original search volume and historical cases were combined. To our knowledge, this is the first study to reduce search engine data bias levels through the use of rigorous spatial sampling strategies.",2016 Jun 6,"['Huang, Da-Cang', 'Wang, Jin-Feng', 'Huang, Ji-Xia', 'Sui, Daniel Z.', 'Zhang, Hong-Yan', 'Hu, Mao-Gui', 'Xu, Cheng-Dong']",PLoS Comput Biol,,,False
ae94b6a3da2521778ce8af0fe653a30a14f74c6a,PMC,Zika Virus Focuses the Gain-of-Function Debate,http://dx.doi.org/10.1128/mSphere.00069-16,PMC4894681,27303723,CC BY,,2016 Apr 6,"['Imperiale, Michael J.', 'Casadevall, Arturo']",mSphere,,,True
a3c43cf529fc26a2f6b039c7e2aa9f0825a9a19f,PMC,A Single Residue in Ebola Virus Receptor NPC1 Influences Cellular Host Range in Reptiles,http://dx.doi.org/10.1128/mSphere.00007-16,PMC4894689,27303731,CC BY,"Filoviruses are the causative agents of an increasing number of disease outbreaks in human populations, including the current unprecedented Ebola virus disease (EVD) outbreak in western Africa. One obstacle to controlling these epidemics is our poor understanding of the host range of filoviruses and their natural reservoirs. Here, we investigated the role of the intracellular filovirus receptor, Niemann-Pick C1 (NPC1) as a molecular determinant of Ebola virus (EBOV) host range at the cellular level. Whereas human cells can be infected by EBOV, a cell line derived from a Russell’s viper (Daboia russellii) (VH-2) is resistant to infection in an NPC1-dependent manner. We found that VH-2 cells are resistant to EBOV infection because the Russell’s viper NPC1 ortholog bound poorly to the EBOV spike glycoprotein (GP). Analysis of panels of viper-human NPC1 chimeras and point mutants allowed us to identify a single amino acid residue in NPC1, at position 503, that bidirectionally influenced both its binding to EBOV GP and its viral receptor activity in cells. Significantly, this single residue change perturbed neither NPC1’s endosomal localization nor its housekeeping role in cellular cholesterol trafficking. Together with other recent work, these findings identify sequences in NPC1 that are important for viral receptor activity by virtue of their direct interaction with EBOV GP and suggest that they may influence filovirus host range in nature. Broader surveys of NPC1 orthologs from vertebrates may delineate additional sequence polymorphisms in this gene that control susceptibility to filovirus infection. IMPORTANCE Identifying cellular factors that determine susceptibility to infection can help us understand how Ebola virus is transmitted. We asked if the EBOV receptor Niemann-Pick C1 (NPC1) could explain why reptiles are resistant to EBOV infection. We demonstrate that cells derived from the Russell’s viper are not susceptible to infection because EBOV cannot bind to viper NPC1. This resistance to infection can be mapped to a single amino acid residue in viper NPC1 that renders it unable to bind to EBOV GP. The newly solved structure of EBOV GP bound to NPC1 confirms our findings, revealing that this residue dips into the GP receptor-binding pocket and is therefore critical to the binding interface. Consequently, this otherwise well-conserved residue in vertebrate species influences the ability of reptilian NPC1 proteins to bind to EBOV GP, thereby affecting viral host range in reptilian cells.",2016 Mar 30,"['Ndungo, Esther', 'Herbert, Andrew S.', 'Raaben, Matthijs', 'Obernosterer, Gregor', 'Biswas, Rohan', 'Miller, Emily Happy', 'Wirchnianski, Ariel S.', 'Carette, Jan E.', 'Brummelkamp, Thijn R.', 'Whelan, Sean P.', 'Dye, John M.', 'Chandran, Kartik']",mSphere,,,True
4997e92b014bb26f8184eae26662a09ffcf4f733,PMC,DGV: Dengue Genographic Viewer,http://dx.doi.org/10.3389/fmicb.2016.00875,PMC4894901,27375595,CC BY,"Dengue viruses (DENVs) and their vectors are widely distributed throughout the tropical and subtropical regions of the world. An autochthonous case of DENV was reported in Tokyo, Japan, in 2014, for the first time in 70 years. A comprehensive database of DENV sequences containing both serotype and genotype data and epidemiological data is crucial to trace DENV outbreak isolates and promptly respond to outbreaks. We constructed a DENV database containing the serotype, genotype, year and country/region of collection by collecting all publically available DENV sequence information from the National Center for Biotechnology Information (NCBI) and assigning genotype information. We also implemented the web service Dengue Genographic Viewer (DGV), which shows the geographical distribution of each DENV genotype in a user-specified time span. DGV also assigns the serotype and genotype to a user-specified sequence by performing a homology search against the curated DENV database, and shows its homologous sequences with the geographical position and year of collection. DGV also shows the distribution of DENV-infected entrants to Japan by plotting epidemiological data from the Infectious Agents Surveillance Report (IASR), Japan. This overview of the DENV genotype distribution may aid in planning for the control of DENV infections. DGV is freely available online at: (https://gph.niid.go.jp/geograph/dengue/content/genomemap).",2016 Jun 7,"['Yamashita, Akifumi', 'Sakamoto, Tetsuya', 'Sekizuka, Tsuyoshi', 'Kato, Kengo', 'Takasaki, Tomohiko', 'Kuroda, Makoto']",Front Microbiol,,,True
7ba06e5c566af08208ee7d87cc8a0d6c2b772b9e,PMC,"Transmission of Hand, Foot and Mouth Disease and Its Potential Driving Factors in Hong Kong",http://dx.doi.org/10.1038/srep27500,PMC4895171,27271966,CC BY,"Hand-foot-and-mouth disease (HFMD) is a common childhood disease with substantial disease burden in Asia. Mixed results were reported on the associations between HFMD incidence and meteorological factors or school holidays, while limited studies focused on their association on transmissibility. We aimed to measure the transmissibility of HFMD and to examine its potential driving factors in Hong Kong. A likelihood-based procedure was used to estimate time-dependent effective reproduction number (R(t)) based on weekly number of HFMD-associated hospitalizations from 2010 to 2014. The associations of between-year effects, depletion of susceptibles, absolute humidity and school holidays with R(t) were examined using linear regression. R(t) usually started increasing between early spring and summer and peaked in April to May at around 1.1–1.2, followed by a slight rebound in autumn. Depletion of susceptibles and between-years effects explained most of the variances (19 and 13% respectively) in R(t). We found a negative association between depletion of susceptibles and R(t) (coefficients ranged from −0.14 to −0.03 for different years), but the estimated effects of absolute humidity and school holidays were insignificant. Overall, HFMD transmission was moderate in Hong Kong and was mainly associated with depletion of susceptibles. Limited impact was suggested from meteorological factors and school holidays.",2016 Jun 7,"['Yang, Bingyi', 'Lau, Eric H. Y.', 'Wu, Peng', 'Cowling, Benjamin J.']",Sci Rep,,,True
2acdee7df15edf13c1f992bc7aed50fa3a193ae6,PMC,"Transmission of Hand, Foot and Mouth Disease and Its Potential Driving Factors in Hong Kong",http://dx.doi.org/10.1038/srep27500,PMC4895171,27271966,CC BY,"Hand-foot-and-mouth disease (HFMD) is a common childhood disease with substantial disease burden in Asia. Mixed results were reported on the associations between HFMD incidence and meteorological factors or school holidays, while limited studies focused on their association on transmissibility. We aimed to measure the transmissibility of HFMD and to examine its potential driving factors in Hong Kong. A likelihood-based procedure was used to estimate time-dependent effective reproduction number (R(t)) based on weekly number of HFMD-associated hospitalizations from 2010 to 2014. The associations of between-year effects, depletion of susceptibles, absolute humidity and school holidays with R(t) were examined using linear regression. R(t) usually started increasing between early spring and summer and peaked in April to May at around 1.1–1.2, followed by a slight rebound in autumn. Depletion of susceptibles and between-years effects explained most of the variances (19 and 13% respectively) in R(t). We found a negative association between depletion of susceptibles and R(t) (coefficients ranged from −0.14 to −0.03 for different years), but the estimated effects of absolute humidity and school holidays were insignificant. Overall, HFMD transmission was moderate in Hong Kong and was mainly associated with depletion of susceptibles. Limited impact was suggested from meteorological factors and school holidays.",2016 Jun 7,"['Yang, Bingyi', 'Lau, Eric H. Y.', 'Wu, Peng', 'Cowling, Benjamin J.']",Sci Rep,,,True
f9e8af068e552f4327e0e7cdd359674967d9d422,PMC,Reducing burden of disease from residential indoor air exposures in Europe (HEALTHVENT project),http://dx.doi.org/10.1186/s12940-016-0101-8,PMC4895703,26961383,CC BY,"BACKGROUND: The annual burden of disease caused indoor air pollution, including polluted outdoor air used to ventilate indoor spaces, is estimated to correspond to a loss of over 2 million healthy life years in the European Union (EU). Based on measurements of the European Environment Agency (EEA), approximately 90 % of EU citizens live in areas where the World Health Organization (WHO) guidelines for air quality of particulate matter sized < 2.5 mm (PM(2.5)) are not met. Since sources of pollution reside in both indoor and outdoor air, selecting the most appropriate ventilation strategy is not a simple and straightforward task. METHODS: A framework for developing European health-based ventilation guidelines was created in 2010–2013 in the EU-funded HEALTHVENT project. As a part of the project, the potential efficiency of control policies to health effects caused by residential indoor exposures of fine particulate matter (PM(2.5)), outdoor bioaerosols, volatile organic compounds (VOC), carbon oxide (CO) radon and dampness was estimated. The analysis was based on scenario comparison, using an outdoor-indoor mass-balance model and varying the ventilation rates. Health effects were estimated with burden of diseases (BoD) calculations taking into account asthma, cardiovascular (CV) diseases, acute toxication, respiratory infections, lung cancer and chronic obstructive pulmonary disease (COPD). RESULTS: The quantitative comparison of three main policy approaches, (i) optimising ventilation rates only; (ii) filtration of outdoor air; and (iii) indoor source control, showed that all three approaches are able to provide substantial reductions in the health risks, varying from approximately 20 % to 44 %, corresponding to 400 000 and 900 000 saved healthy life years in EU-26. PM(2.5) caused majority of the health effects in all included countries, but the importance of the other pollutants varied by country. CONCLUSIONS: The present modelling shows, that combination of controlling the indoor air sources and selecting appropriate ventilation rate was the most effective to reduce health risks. If indoor sources cannot be removed or their emissions cannot be limited to an accepted level, ventilation needs to be increased to remove remaining pollutants. In these cases filtration of outdoor air may be needed to prevent increase of health risks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12940-016-0101-8) contains supplementary material, which is available to authorized users.",2016 Mar 8,"['Asikainen, Arja', 'Carrer, Paolo', 'Kephalopoulos, Stylianos', 'Fernandes, Eduardo de Oliveira', 'Wargocki, Pawel', 'Hänninen, Otto']",Environ Health,,,True
c5375b07f72048d739efc376420a5cb5374392d6,PMC,Reducing burden of disease from residential indoor air exposures in Europe (HEALTHVENT project),http://dx.doi.org/10.1186/s12940-016-0101-8,PMC4895703,26961383,CC BY,"BACKGROUND: The annual burden of disease caused indoor air pollution, including polluted outdoor air used to ventilate indoor spaces, is estimated to correspond to a loss of over 2 million healthy life years in the European Union (EU). Based on measurements of the European Environment Agency (EEA), approximately 90 % of EU citizens live in areas where the World Health Organization (WHO) guidelines for air quality of particulate matter sized < 2.5 mm (PM(2.5)) are not met. Since sources of pollution reside in both indoor and outdoor air, selecting the most appropriate ventilation strategy is not a simple and straightforward task. METHODS: A framework for developing European health-based ventilation guidelines was created in 2010–2013 in the EU-funded HEALTHVENT project. As a part of the project, the potential efficiency of control policies to health effects caused by residential indoor exposures of fine particulate matter (PM(2.5)), outdoor bioaerosols, volatile organic compounds (VOC), carbon oxide (CO) radon and dampness was estimated. The analysis was based on scenario comparison, using an outdoor-indoor mass-balance model and varying the ventilation rates. Health effects were estimated with burden of diseases (BoD) calculations taking into account asthma, cardiovascular (CV) diseases, acute toxication, respiratory infections, lung cancer and chronic obstructive pulmonary disease (COPD). RESULTS: The quantitative comparison of three main policy approaches, (i) optimising ventilation rates only; (ii) filtration of outdoor air; and (iii) indoor source control, showed that all three approaches are able to provide substantial reductions in the health risks, varying from approximately 20 % to 44 %, corresponding to 400 000 and 900 000 saved healthy life years in EU-26. PM(2.5) caused majority of the health effects in all included countries, but the importance of the other pollutants varied by country. CONCLUSIONS: The present modelling shows, that combination of controlling the indoor air sources and selecting appropriate ventilation rate was the most effective to reduce health risks. If indoor sources cannot be removed or their emissions cannot be limited to an accepted level, ventilation needs to be increased to remove remaining pollutants. In these cases filtration of outdoor air may be needed to prevent increase of health risks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12940-016-0101-8) contains supplementary material, which is available to authorized users.",2016 Mar 8,"['Asikainen, Arja', 'Carrer, Paolo', 'Kephalopoulos, Stylianos', 'Fernandes, Eduardo de Oliveira', 'Wargocki, Pawel', 'Hänninen, Otto']",Environ Health,,,True
d3faa41624a8a99e5f600923cbe61fc457fb76a6,PMC,Nonstructural protein 11 (nsp11) of porcine reproductive and respiratory syndrome virus (PRRSV) promotes PRRSV infection in MARC-145 cells,http://dx.doi.org/10.1186/s12917-016-0717-5,PMC4895886,27268206,CC BY,"BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) induces one of most important devastating disease of swine worldwide, and the current methods poorly control it. Previous studies have indicated that the nonstructural protein 11 (nsp11) of PRRSV may be an important protein for the immune escape of PRRSV. RESULTS: Here, we firstly explored the effect of over-expression of nsp11 on PRRSV infection and found that over-expression of nsp11 enhanced the PRRSV titers while the small interfering RNA (siRNAs) specifically targeting nsp11 could reduce the PRRSV titers in MARC-145 cells. CONCLUSION: In conclusion, PRRSV nsp11 promotes PRRSV infection in MARC-145 cells and siRNAs targeting nsp11 may be a potential therapeutic strategy to control PRRSV in future.",2016 Jun 6,"['Shi, Xibao', 'Zhang, Xiaozhuan', 'Chang, Yongzhe', 'Jiang, Bo', 'Deng, Ruiguang', 'Wang, Aiping', 'Zhang, Gaiping']",BMC Vet Res,,,True
962c3880e4fee95b974d6d754a568278cc72e6d7,PMC,Medicinal plants – prophylactic and therapeutic options for gastrointestinal and respiratory diseases in calves and piglets? A systematic review,http://dx.doi.org/10.1186/s12917-016-0714-8,PMC4896019,27268043,CC BY,"BACKGROUND: Gastrointestinal and respiratory diseases in calves and piglets lead to significant economic losses in livestock husbandry. A high morbidity has been reported for diarrhea (calves ≤ 35 %; piglets ≤ 50 %) and for respiratory diseases (calves ≤ 80 %; piglets ≤ 40 %). Despite a highly diverse etiology and pathophysiology of these diseases, treatment with antimicrobials is often the first-line therapy. Multi-antimicrobial resistance in pathogens results in international accordance to strengthen the research in novel treatment options. Medicinal plants bear a potential as alternative or additional treatment. Based on the versatile effects of their plant specific multi-component-compositions, medicinal plants can potentially act as ‘multi-target drugs’. Regarding the plurality of medicinal plants, the aim of this systematic review was to identify potential medicinal plant species for prevention and treatment of gastrointestinal and respiratory diseases and for modulation of the immune system and inflammation in calves and piglets. RESULTS: Based on nine initial sources including standard textbooks and European ethnoveterinary studies, a total of 223 medicinal plant species related to the treatment of gastrointestinal and respiratory diseases was identified. A defined search strategy was established using the PRISMA statement to evaluate 30 medicinal plant species starting from 20’000 peer-reviewed articles published in the last 20 years (1994–2014). This strategy led to 418 references (257 in vitro, 84 in vivo and 77 clinical trials, thereof 48 clinical trials in veterinary medicine) to evaluate effects of medicinal plants and their efficacy in detail. The findings indicate that the most promising candidates for gastrointestinal diseases are Allium sativum L., Mentha x piperita L. and Salvia officinalis L.; for diseases of the respiratory tract Echinacea purpurea (L.) MOENCH, Thymus vulgaris L. and Althea officinalis L. were found most promising, and Echinacea purpurea (L.) MOENCH, Camellia sinensis (L.) KUNTZE, Glycyrrhiza glabra L. and Origanum vulgare L. were identified as best candidates for modulation of the immune system and inflammation. CONCLUSIONS: Several medicinal plants bear a potential for novel treatment strategies for young livestock. There is a need for further research focused on gastrointestinal and respiratory diseases in calves and piglets, and the findings of this review provide a basis on plant selection for future studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0714-8) contains supplementary material, which is available to authorized users.",2016 Jun 6,"['Ayrle, Hannah', 'Mevissen, Meike', 'Kaske, Martin', 'Nathues, Heiko', 'Gruetzner, Niels', 'Melzig, Matthias', 'Walkenhorst, Michael']",BMC Vet Res,,,True
023858d3191988a37587ab951db561a3db3ae2cd,PMC,Evaluation of custom multiplex real - time RT - PCR in comparison to fast - track diagnostics respiratory 21 pathogens kit for detection of multiple respiratory viruses,http://dx.doi.org/10.1186/s12985-016-0549-8,PMC4896093,27267595,CC BY,"BACKGROUND: Severe acute respiratory infections in children can be fatal, rapid identification of the causative agent and timely treatment can be life saving. Multiplex real time RT-PCR helps in simultaneous detection of multiple viruses saving cost, time and labour. Commercially available multiplex real time RT-PCR kits are very expensive. Therefore the aim of the present study was to develop a cost effective multiplex real time RT-PCR for the detection of 18 respiratory viruses and compare it with an in-vitro diagnostics approved Fast Track Diagnostic Respiratory Pathogens 21 Kit (FTD). METHODS: Nasopharyngeal aspirates and throat swabs were collected and processed for extraction of nucleic acid using an automated extraction system and multiplex real time RT-PCR was performed using the FTD kit and a custom assay on 356 samples. RESULTS: Custom and FTD assays detected one or more respiratory viruses in 268 (75.29 %) and 262 (73.60 %) samples respectively. The concordance between the custom assay and the FTD assay was 100 % for HCoV OC43, HCoV 229E, HPIV-1, HPIV-2, HBoV, HPeV, Flu A, and Influenza A(H1N1)pdm09 and 94.66 – 99.71 % for the remaining viruses; Flu B (99.71 %), HRV (99.71 %), HPIV-3 (98.87 %), HPIV-4 (99.43 %), HCoV NL63 (99.71 %), HMPV A/B (99.71 %), RSV A/B (94.66 %), EV (98.31 %), HCoV HKU1 (99.71 %), HAdV (99.71 %). Major discrepancy was observed for RSV A/B, which was over detected in 18 samples by the custom assay as compared to the FTD assay. The custom assay was much cheaper than the FTD assay and the time taken was only 29 min more. CONCLUSION: The custom primer and probe mix was found to be comparable to the FTD assay with good concordance but was much cheaper and the time taken for reporting was only 29 min more. The low cost custom multiplex RT-PCR can be a useful alternative to the costly FTD kit for rapid identification of viral aetiology in resource limited settings.",2016 Jun 6,"['Malhotra, Bharti', 'Swamy, M. Anjaneya', 'Reddy, P. V. Janardhan', 'Kumar, Neeraj', 'Tiwari, Jitendra Kumar']",Virol J,,,True
a5293bb4f17ad25a72133cdd9eee8748dd6a4b8d,PMC,"XXIV World Allergy Congress 2015: Seoul, Korea. 14-17 October 2015",http://dx.doi.org/10.1186/s40413-016-0096-1,PMC4896250,,CC BY,"A1 Pirfenidone inhibits TGF-b1-induced extracellular matrix production in nasal polyp-derived fibroblasts Jae-Min Shin, Heung-Man Lee, Il-Ho Park A2 The efficacy of a 2-week course of oral steroid in the treatment of chronic spontaneous urticaria refractory to antihistamines Hyun-Sun Yoon, Gyeong Yul Park A3 The altered distribution of follicular t helper cells may predict a more pronounced clinical course of primary sjögren’s syndrome Margit Zeher A4 Betamethasone suppresses Th2 cell development induced by langerhans cell like dendritic cells Katsuhiko Matsui, Saki Tamai, Reiko Ikeda A5 An evaluation of variousallergens in cases of allergic bronchial asthma at lucknow and neighbouring districts by intradermal skintest Drsushil Suri, Dranu Suri A6 Evaluation ferqency of ADHD in childhood asthma Marzieh Heidarzadeh Arani A7 Steven johnson syndrome caused by typhoid fever in a child Azwin Lubis, Anang Endaryanto A8 Chronic Bronchitis with Radio Contrast Media Hypersensitivity: A Case with Hypothesized GINA Step 1 Asthma Shinichiro Koga A9 The association between asthma and depression in Korean adult : An analysis of the fifth korea national health and nutrition examination survey (2010-2012) Lee Ju Suk A10 Management of allergic disease exacerbations in pregnancy Yasunobu Tsuzuki A11 Subcutaneous immunotherapy mouse model for atopic dermatitis Seo Hyeong Kim, Jung U Shin, Ji Yeon Noh, Shan Jin, Shan Jin, Hemin Lee, Jungsoo Lee, Chang Ook Park, Kwang Hoon Lee, Kwang Hoon Lee A12 Atopic disease and/or atopy are risk factors for local anesthetic allergy in patients with history of hypersensitivity reactions to drugs? Fatma Merve Tepetam A13 Food hypersensitivity in patients with atopic dermatitis in Korea Chun Wook Park, Jee Hee Son, Soo Ick Cho, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Hye One Kim, Hee Jin Cho A14 Anaphylaxis caused by an ant (Brachyponera chinensis) in Japan Yoshinori Katada, Toshio Tanaka, Akihiko Nakabayashi, Koji Nishida, Kenichi Aoyagi, Yuki Tsukamoto, Kazushi Konma, Motoo Matsuura, Jung-Won Park, Yoshinori Harada, Kyoung Yong Jeong, Akiko Yura, Maiko Yoshimura A15 Anti-allergic effect of anti-IL-33 by suppression of immunoglobulin light chain and inducible nitric oxide synthase Tae-Suk Kyung, Young Hyo Kim, Chang-Shin Park, Tae Young Jang, Min-Jeong Heo, Ah-Yeoun Jung, Seung-Chan Yang A16 Food hypersensitivity in patients with chronic urticaria in Korea Hye One Kim, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Jee Hee Son, Chun Wook Park, Hee Jin Cho A17 Dose optimizing study of a depigmented polymerized allergen extract of phleum pollen by means of conjunctival provocation test (CPT) Angelika Sager, Oliver Pfaar A18 Correlation of cutaneous sensitivity and cytokine response in children with asthma Amit Agarwal, Meenu Singh, Bishnupda Chatterjee, Anil Chauhan A19 Colabomycin E, a Streptomycete-Derived Secondary Metabolite, Inhibits Proinflammatory Cytokines in Human Monocytes/Macrophages Ilja Striz, Eva Cecrdlova, Katerina Petrickova, Libor Kolesar, Alena Sekerkova, Veronika Svachova, Miroslav Petricek A20 Intravenous immunoglobluin treatment in a child with resistant atopic dermatitis: A brief review on this therapeutic regimen Hyuck Hoon Kwon, Kyu Han Kim A21 Wheat allergy is difficult to diagnose then other food allergens Suman Kumar A22 The effects of spirulina (Arthrospira platensis) dietary supplement as an adjunct therapy for children aged 7 to 14 years old with asthma: A randomized - double blind placebo controlled clinical trial Lou Ver Leigh Arciaga Manzon, Pilar Agnes Gonzalez Andaya A23 The study about cause and clinicopathological findings of injection induced dermatitis Bark-Lynn Lew, Youngjun Oh, Dongwoo Suh, Woo-Young Sim A24 IgE reactivity of recombinant allergen pac c 3 of the Asian needle ant pachycondyla chinensis Kyoung Yong Jeong, Myung-Hee Yi, Mina Son, Dongpyo Lyu, Jae-Hyun Lee, Tai-Soon Yong, Chein-Soo Hong, Jung-Won Park A25 Characterization of specific IgE antibody related to antigen 5 of echinococcus granulosus Mohammadreza Siavashi A26 Development of binary forecast model of asthma exacerbation: Asthma index Hey Suk Yun, Ha-Na Kang, Jae-Won Oh, Young Jin Choi A27 Different levels in rantes, IL-5 and TNF-á between the nasal polyps of adolescents with allergic, local allergic and non-allergic rhinitis Ha-Na Kang, Jae-Won Oh, Young Jin Choi A28 Tgfβ1 level is associated with VDR gene polymorphism in children with allergy diseases Tatiana Sentsova, Ilya Vorozhko, Olga Chernyak, Vera Revyakina, Anna Timopheeva, Andrey Donnikov A29 Dynamics of immunological biomarkers in children with food allergy fed goat milk formula Tatiana Sentsova, Ilya Vorozhko, Olga Chernyak, Vera Revyakina, Anna Timopheeva A30 Association between obesity, abdominal obesity and adiposity and the prevalence of atopic dermatitis in young Korean adults: The korea national health and nutrition examination survey, 2008–2010 Ji Hyun Lee, Young Min Park, Sang Soo Choi, Kyung Do Han, Han Mi Jung, Young Hoon Youn, Jun Young Lee, Yong Gyu Park, Seung-Hwan Lee A31 Associations of natural history and environmental factors with asthma among children in rural and urban areas of guangdong, China Zhaowei Yang, Jing Li, Mulin Feng, Marjut Roponen, Bianca Schaub, Gary WK Wong A32 The effect of CO2-enriched atmospheres to producing of allergenic pollen by ragweed Young Jin Choi, Ha-Na Kang, Jae-Won Oh A33 Application evaluation of house dust mite and components specific-IgE and IgG4 in specific immunotherapy with allergic diseases Baoqing Sun, Peiyan Zheng A34 Effect of Asian dust events on asthma according to the socioeconomic status using claim data in KOREA Yoon-Sung Park A35 TSLP downregulates human â-defensin 2 through STAT3-dependent pathway in keratinocytes Sang Wook Son A36 Effects of anti-IgE on IL-4, IL-5, IL-17, and CD19,20,200 in a case of netherton syndrome (SPINK5 mutation) Arzu Didem Yalcin, Sukran Kose, Kemal Kiraz A37 Augmentation of arginase 1 expression exacerbates airway inflammation in murine asthma models Jin-Young Lee, Sehyo Yune, Jae-Won Paeng, Mi-Jung Oh, Byung-Jae Lee, Dong-Chull Choi, Young Hee Lim, Kyoung Won Ha A38 Caregivers of children with no food allergy – their experiences and perception of the condition Kiwako Yamamoto-Hanada, Masami Narita, Masaki Futamura, Yukihiro Ohya A39 Evaluation of Drug Provocation Tests in Korean Children: A Single Center Experience Jihyun Kim, Jinwha Choi, Kwanghoon Kim, Jaehee Choi, Kangmo Ahn A40 Danyoung classification 2015 update by digital HD endoscopic evaluation SUN-HO/Brian Chang A41 Effect on quality of life of the mixed house dust mite/weed pollen extract immunotherapy in polysensitized patients Lisha Li A42 Ambient desert dust and allergic symptoms: A time series analysis from a national birth cohort (JECS) Kumiko Tsuji Kanatani, Yu-Ichi Adachi A43 Individuals Allergic to Cow’s Milk Should be Vigilant When Consuming Beef Because It May be Injected Beef Shigeyuki Narabayashi, Ikuo Okafuji, Yuya Tanaka, Satoru Tsuruta, Nobue Takamatsu A44 Quality of life of chronic rhinosinusitis patients with or without nasal polyps in Korea Soo Whan Kim, Do Hyun Kim A45 House dust mite sensitization and exacerbation of asthma in the fall in children Jong-Seo Yoon, Jin Tack Kim, Hwan Soo Kim, Yoon Hong Chun, Hyun Hee Kim, Sul Mui Won A46 Evidence-based health advice for childhood eczema and household pets Kam Lun E. Hon, Chung Mo Chow, Ting Fan Leung A47 Relationship between allergic rhinitis and mental health in korea Do Hyun Kim, Soo Whan Kim A48 Oscillometric bronchodilator response in 3 to 5 years old healthy and asthmatic Filipino children Gemmalyn Esguerra, Emily Resurreccion, Kristine Elisa Kionisala, Jenni Rose Dela Cruz A49 The use of aeroallergen immunotherapy to treat eosinophilic esophagitis Muhammad Imran A50 A study of the eczema herpeticum in Korean Yun Seon Choe, Kyu Han Kim, Mira Choi A51 Specific sublingual immunotherapy in Korean patients with atopic dermatitis Byung Soo Kim, Hyun-Joo Lee, Jeong-Min Kim, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Je-Ho Mun, Hoon-Soo Kim, Margaret Song, Hyun-Chang Ko, Hyun-Chang Ko, Moon-Bum Kim A52 Association between polymorphisms in bitter taste receptors genes and clinical features in Korean asthmatics Sun-Young Yoon A53 Effect of glycosides based standardized fenugreek seed extract in bleomycin-induced pulmonary fibrosis in rats Amit Kandhare A54 A kampo formula, ogi-kenchu-to, decreases side-effects of steroid ointment for infantile atopic dermatitis: Three cases report Noriko Yahiro A55 To test use of jet nebulizers NE-C802 as a drug delivery system in the children with asthma Amit Agarwal, Meenu Singh, Jasleen Kaur, Ruby Pawankar, Pankaj Pant, Sukhmanjeet Singh A56 Immunoglobulin e to allergen components of house dust mite in Korean children with allergic disease Hwan Soo Kim, Jong-Seo Yoon, Sul Mui Won, Yoon Hong Chun, Jin Tack Kim, Hyun Hee Kim A57 Effectiveness of premedication and rapid desensitization in hypersensitivity to l-asparaginase Hwan Soo Kim, Sul Mui Won, Yoon Hong Chun, Jong-Seo Yoon, Hyun Hee Kim, Jin Tack Kim A58 Angioedema with Eosinophilia: The First Report from Thailand Thatchai Kampitak A59 Evaluation of anti-pruritic and anti-inflammatory effects of Korean red ginseng extract on atopic dermatitis murine model So Min Kim, Hyun Joo Lee, Hei Sung Kim, Jeong Deuk Lee, Sang Hyun Cho A60 Subcutaneous autologous serum therapy in chronic urticaria Kiran Godse A61 Allergic bronchopulmonary aspergillosis in asthma and lung tuberculosis Juwita Soekarno, Sarie Ratnasari, E. Alwi Datau, Eko Surachmanto, JC Matheos A62 Infantile eczema is associated with campylobacter and roseburia subpopulations but not microbial diversity in stool samples of Chinese newborns Ting Fan Leung, Jamie Sui-Lam Kwok, Christine Kit-Ching Tung, Man Fung Tang, Stephen Kwok-Wing Tsui, Gary WK Wong, Kam Lun Ellis Hon, Wing Hung Tam, Hing Yee Sy A63 Association between serum chitinase level and toll-like receptor polymorphisms in bakery workers Sohee Lee A64 IFN-gamma contributes to nasal polypogenesis by inducing epithelial-to-mesenchymal transition via non-smad pathway Hyun-Woo Shin, Mingyu Lee, Dae Woo Kim, Roza Khalmuratova A65 Management and education status of anaphylaxis patients who visit our emergency room (ER) Mi Yeoung Kim, Jaewon Jeong, Chansun Park A66 Hypoallergen-Encoding DNA Plasmids As Immunoprophylactic Vaccines of Shrimp Tropomyosin Hypersensitivity Christine Yee Yan Wai, Patrick S.C. Leung, Nicki Y.H. Leung, Ka Hou Chu A67 The relationship between sputum pentraxin 3 levels and childhood asthma Hee Seon Lee, Kyung Eun Lee, Jung Yeon Hong, Mi Na Kim, Min Jung Kim, Yoon Hee Kim, In Suk Sol, Seo Hee Yoon, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim A68 The role of local antibody responses in the nasal inflammation of allergic rhinitis (AR) patients Ji Hye Kim, Hae-Sim Park, Yoo Seob Shin, Young Min Ye, Daehong Seo, Moon Gyeong Yoon, Young Mok Lee A69 A case of ofloxacin-induced anaphylaxis by non-IgE, but specific IgG4-mediated responses Daehong Seo, Ji Hye Kim, Young-Mok Lee, Young Min Ye, Hae-Sim Park A70 Serum LTE4 metabolite as a biomarker for aspirin exacerbated respiratory disease Ga Young Ban, Kumsun Cho, Seung-Hyun Kim, Yong Eun Kwon, Moon Gyeong Yoon, Ji Hye Kim, Yoo Seob Shin, Young Min Ye, Dong-Ho Nahm, Hae-Sim Park A71 Local and systemic reactions of dust mite subcutaneous immunotherapy (SCIT) among children in a tertiary care hospital Pilar Agnes Gonzalez Andaya A72 Effects of carboxymethyl glucan (CM-glucan) in children with allergic rhinitis and asthma: A randomized controlled trial Pilar Agnes Gonzalez Andaya A73 Autophagy mechanisms in patients with severe asthma: A new therapeutic target Ga Young Ban, Chang Gyu Jung, Seung-Ihm Lee, Duy Le Pham, Dong-Hyeon Suh, Eun-Mi Yang, Young Min Ye, Yoo Seob Shin, Hae-Sim Park A74 Aggravation of airway inflammation and hypperresponsiveness following nasal challenge with dermatophagoides pteronyssinus in perennial allergic rhinitis patients without symptoms of asthma Wan Jun Wang, MO Xian, Yan Qing Xie, Jing Ping Zheng, Jing Li A75 Serum 25-hydroxyvitamin d in early childhood is non-linearly associated with allergy Emma Merike Savilahti, Outi Mäkitie, Anna Kaarina Kukkonen, Sture Andersson, Heli Viljakainen, Erkki Savilahti, Mikael Kuitunen A76 Fric test in dermographism Kiran Godse A77 Neutrophil autophagy and extracellular trap could contribute to asthma severity Duy Le Pham, Ga Young Ban, Seung-Hyun Kim, Eun-Mi Yang, Hae-Sim Park, Ji-Ho Lee, Yong-Joon Chwae A78 Redox Modulation for the Treatment of Toluene Diisocyanates-Induced Lung Inflammation Li-Ming Chin, Chi-Chang Shieh A79 A case of occupational asthma and rhinitis with anaphylaxis to Korean ginseng and sanyak Ji Hye Kim, Hye-Soo Yoo, Moon Gyeong Yoon, Ga Young Ban, Ga Young Ban, Yoo Seob Shin, Young Min Ye, Hae-Sim Park A80 Factors of influencing epidermal permeability barrier defects in atopic dermatitis children Myong Soon Sung, Jin Uck Choi, Sung Won Kim, Yong Jin Hwang A81 Innate type 2 response to aspergillusfumigatus in a murine model of atopic dermatitis-like skin inflammation Arum Park, Eun Lee, Song-I Yang, Hyun-Ju Cho, Jinho Yu A82 Activin a receptor 1C may implicate in the development of sensitive skin Dong Hun Lee, Eun Ju Kim, Yeon Kyung Kim, Eun Jin Doh, Hee Chul Eun, Jin Ho Chung, Young Mee Lee, Seon Pil Jin A83 Genetic association and eQTL analyses of genes associated with allergy in atopic/non-atopic asthma Xingnan Li, Naftali Kaminski, Sally Wenzel, Eugene Bleecker, Deborah Meyers A84 Gastroscope feature and clinical characteristics in 172 cases of children with henoch-schonlein purpura Zeng Huasong A85 The role of TRPV1 in CD4+ t cell mediated inflammatory response of allergic rhinitis Ji-Hun Mo, Ramachandran Samivel, Eun-Hee Kim, Ji-Hye Kim, Jun-Sang Bae, Young-Jun Chung, Dae Woo Kim A86 A Phenotype of Rhinitis from School Children Is Associated with the Development of Bronchial Hyperresponsiveness Eun Lee, Si Hyeon Lee, Young-Ho Kim, Hyun-Ju Cho, Ho-Sung Yu, Mi-Jin Kang, Song-I Yang, Young-Ho Jung, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, So-Yeon Lee, Ho-Jang Kwon, Soo-Jong Hong A87 Increased basal activation status was noted in adult anaphylaxis patients Sailesh Palikhe, Hae-Sim Park, Seung-Hyun Kim, Ji Hye Kim, Eun-Mi Yang A88 Clinical values of interferon-gamma enzyme-linked immunospot assays for management of antibiotic hypersensitivity in hospitalized patients Suda Sibunruang, Jettanong Klaewsongkram A89 VDR gene polymorphism and 25-hydroxy vitamin d levels in children with food allergy Tatiana Sentsova, Ilya Vorozhko, Anna Timopheeva, Olga Chernyak, Vera Revyakina, Andrey Sokolnikov A90 An analysis of 145 oral almond challenge tests Makoto Nisihino, Yu Okada, Noriyuki Yanagida, Motohiro Ebisawa, Sakura Sato, Kiyotake Ogura, Tomoyuki Asaumi, Kenichi Nagakura, Tetsuharu Manabe, Hirotoshi Unno A91 Effect of creatine supplementation in fish allergenic potential; A proteomics study Pedro M Rodrigues, Denise Schrama, Gadija Mohamed, Lizex Hüsselmann, Lizex Hüsselmann, Bongani Ndimba A92 Flagellin modulates the function of invariant NKT cells via dendritic cells in asthma patients Jae-Uoong Shim, Young Il Koh, Joon Haeng Rhee, Ji-Ung Jeong A93 Clinical and subclinical manifestations of allopurinol – induced severe cutaneous adverse reactions in Vietnam Dinh Van Nguyen, Hieu Chi Chu, Mui Thi Tran, Christopher Vidal, Suran Fernando, Sheryl Van Nunen, Sy Van Than A94 Time course of serum inhibitory activity for facilitated allergen-IgE binding during house dust mite immunotherapy Mulin Feng, Jing Li A95 Periostin is a novel biomarker in eosinophilic nasal polyps of chronic rhinosinusitis Dong-Kyu Kim, Seung-No Hong, Kyoung Mi Eun, Hong Ryul Jin, Dae Woo Kim A96 Dominance of Th1-response in children with refractory mycoplasma pneumoniae pneumonia Jun Bao, Yi-Xiao Bao A97 Studies on the role of CD14 polymorphism among pollen and mold induced asthmatics of kolkata, India Sanjoy Podder, Goutam Kumar, Shampa Dutta, Amlan Ghosh A98 House dust mite allergy – Indian perspective Goutam Kumar Saha, Sanjoy Podder, Salil Kumar Gupta A99 Increased expression of purinergic (P2Y12) receptor and cysteinyl leukotriene receptors in the lung tissue of a mouse model of allergic asthma Tu/Hoang Kim Trinh, Yoo Seob Shin, Hae-Sim Park, Jing-Nan Liu, Duy Le Pham A100 Autologous serum skin test in chronic idiopathic urticaria - relationship with autoimmune markers and disease severity Hyun-Chang Ko, Byung Soo Kim, Moon-Bum Kim A101 Anxiety and depression levels in severe asthma patients treated with omalizumab Ömer Özbudak, Fatih Üzer A102 Economic burden of refractory chronic spontaneous urticaria on Kuwait health system Mona Al-Ahmad, Maryam Alowayesh, Norman Carroll A103 IgE-mediated maize allergy in India: A 28 kd protein responsible for food-induced allergic reaction Anand Bahadur Singh A104 Liposomal encapsulation of house dust mite allergens and dexamethasone modulates allergic response in a murine model of asthma Yordanis Pérez-Llano, María Del Carmen Luzardo Lorenzo, Wendy Ramírez González, Carlos Calcines Cruz, Rady Laborde Quintana, Alain Morejón, Virgilio Bourg, Marilé Hechavarría Stoker A105 Immune Suppressive Effects of Tonsil-Derived Mesenchymal Stem Cells for Eosinophilic Rhinosinusitis with Nasal Polyps in a Mouse Model Jun-Sang Bae, Ramachandran Samivel, Eun-Hee Kim, Ji-Hye Kim, Ji-Hun Mo A106 Second line treatments of dermographic urticaria refractory to antihistamines Keiko Hanaoka, Michihiro Hide, Akio Tanaka, Makiko Hiragun, Mikio Kawai A107 Diagnostic Value of Specific IgE to Peanut and Ara h 2 in Korean Children with Peanut Allergy Kwanghoon Kim, Kwanghoon Kim, Hye-Young Kim, Jihyun Kim, Kangmo Ahn, Youngshin Han A108 Inappropriate amounts of topical tacrolimus applied on Korean patients with eczema Gun-Wook Kim, Hyun-Chang Ko, Byung Soo Kim, Moon-Bum Kim, Margaret Song A109 Identification of an IgG1-mediated anaphylaxis marker and its application in evaluating the antigenicity of infant formulas Takeshi Matsubara, Hiroshi Iwamoto, Yuki Nakazato, Kazuyoshi Namba, Yasuhiro Takeda A110 Nitric oxide as a screening tool for evaluation of postoperative state of chronic rhinosinusitis Jae Hoon Lee, Woo Yong Bae A111 Comparison of different medical treatment options for crswnp: Doxycycline, methylprednisolone, mepolizumab, omalizumab Els De Schryver, Lien Calus, Philippe Gevaert, Thibaut Van Zele, Claus Bachert A112 Successful treatment of steroid resistant asthma model by blocking CD28 signal Akio Mori, Satoshi Kouyama, Miyako Yamaguchi, Yo Iijima, Akemi Abe-Ohtomo, Hiroaki Hayashi, Kentaroh Watai, Chihiro Mitsui, Chiyako Oshikata, Kiyoshi Sekiya, Takahiro Tsuburai, Mamoru Ohtomo, Yuma Fukutomi, Masami Taniguchi A113 Serum periostin levels was not associated with allergic rhinitis and allergic sensitization in Korean children Ju Wan Kang, Jeong Hong Kim, Jeong Hong Kim, Keun-Hwa Lee, Hye-Sook Lee, Seong-Chul Hong, Jaechun Lee A114 Roles of ADAM10 and ADAM17 in allergic rhinitis Ji Won Seo, Jae Hoon Lee, Woo Yong Bae A115 Mechanism of oral and topical polyprenol action in atopic dermatitis Ivans Sergejs Kuznecovs, Galina Kuznecova A116 Technical and clinical validation of a mobile chamber for allergen exposure tests Karl-Christian Bergmann, Torsten Zuberbier, Joseph Salame, Torsten Sehlinger, Georg Bölke A117 The association between serum lead level and total immunoglobulin e according to allergic sensitization Yoo Suk Kim, Jung Hyun Chang, Jeong Hong Kim, Ju Wan Kang A118 Clinical and laboratory characteristics of nasal obstruction dominant allergic sensitization Seung-No Hong, Doo Hee Han, Chae-Seo Rhee A119 Nasal provocation test is useful for the diagnoses of allergic, non- allergic, and local allergic rhinitis Young-Joo Ko, Young Hyo Kim, Dae-Young Kim, Tae Young Jang A120 Aspirin facilitates the intestinal absorption and oral sensitization of food allergens in rats Tomoharu Yokooji, Taiki Hirano, Hiroaki Matsuo A121 Gestational Secondhand Smoke Exposure Could Affect Maternal n-Glycosylation and Cause Filaggrin Loss in Children with Atopic Dermatitis Galina Kuznecova, Ivans Sergejs Kuznecovs A122 Allergen specific immunotherapy in the treatment of allergic rhinitis and asthma--a randomized prospective study from kashmir valley-north of India Roohi Rasool Wani, Shafia Alam Syed, Ghulam Hassan, Ayaz Gul, Saniya Nissar, Zaffar Amin Shah A123 Sleep disorders in latin-American children with asthma and/or allergic rhinitis and normal controls Marilyn Urrutia Pereira, Carmen Fernandez, Dirceu Sole, Herberto Jose Chong Neto, Veronica Acosta, Alfonso Mario Cepeda, Mirta Alvarez Castello, Claudia Almendarez, Jose Santos Lozano Saenz, Juan C. Sisul, Nelson Rosario Filho, Antonio Castillo, Marylin Valentin Rostan, Jennifer Avila, Hector Badellino, Maria Carolina Manotas, Raúl Lázaro Castro Almarales, Mayda González León A124 Association between respiratory symptoms and exhaled nitric oxide in Afghanistan Woo Kyung Kim, Hae-Sun Yoon A125 ATP, a danger signal, activates human eosinophils via P2 purinergic receptors Takehito Kobayashi, Tooru Noguchi, Tomoyuki Soma, Kazuyuki Nakagome, Hidetomo Nakamoto, Hirohito Kita, Makoto Nagata A126 Atopic dermatitis and sleep disorders in latin American children Marilyn Urrutia Pereira, Dirceu Sole, Herberto Jose Chong Neto, Alfonso Mario Cepeda, Raúl Lázaro Castro Almarales, Juan C. Sisul, Marylin Valentin Rostan, Hector Badellino, Miguel Alejandro Medina Avalos, Antonio Castillo, Claudia Almendarez, Nelson Rosario Filho, Caridad Sanchez Silot, Jennifer Avila, Felicia Berroa Rodriguez, Jose Santos Lozano Saenz, Mirta Alvarez Castello, Carmen Fernandez A127 Der p 23: A Major House Dust Mite Allergen in Spite of Limited Release from Fecal Pellets and Prominent Protease Sensitivity Wai Tuck Soh, Alain Jacquet, Kiat Ruxrungtham, Emmanuel Nony, Maxime Le Mignon A128 Anaphylactic Reaction After Inhalation of Budesonide Mary Lee-Wong, Suzanne McClelland, Suzanne McClelland, Nanette B. Silverberg, Christian E. Song A129 Lipidomic analysis of mattress dust from urban and rural schoolchildren in China Zhaowei Yang, Jiukai Zhang, Wentao Zheng, Nanshan Zhong, Jing Li A130 Improvements in quality of life in children with allergic rhinitis after adenotonsillectomy Jung Ho Bae, Young Joo Cho, Joo Yeon Kim A131 The seasonal variation of asthma exacerbations in patients allergic to pollens in Greece Konstantinos Petalas, Dimitrios Vourdas, Christos Grigoreas A132 Whole-genome sequencing study in allergic rhinitis nuclear families Yuan Zhang A133 Effect of the production of extracellular matrix from nasal fibroblasts by eosinophils activated with airborne fungi Seung-Heon Shin, Mi-Kyung Ye, Jeong-Kyu Kim A134 The study of clinical characteristics, lung function and bronchodilator responsiveness in infants with RSV bronchiolitis Yong Feng, Yunxiao Shang A135 GIS-based association between PM10 and allergic diseases in seoul: Implication for health and environmental policy Sungchul Seo, Ji Tae Choung, Dohyeong Kim, Young Yoo, Hyunwook Lim A136 The relationship between rhinovirus and recurrent wheezing Wenjing Zhu, Chuanhe Liu, Li Sha, Li Chang, Min Zhao, Linqing Zhao, Yuan Qian, Yuzhi Chen A137 Dominancy of Staphylcoccus Aureus in the Skin of Atopic Dermatitis Patients Compared to Healthy Subjects through Metagenomic Analysis Min-Hye Kim, Young Joo Cho, Mina Rho, Jung-Won Kim, Yeon-Mi Kang, Kyung-Eun Yum, Hyeon-Il Choi, Jun-Pyo Choi, Han-Ki Park, Taek-Ki Min, Bok-Yang Pyun, Yoon-Keun Kim A138 Micronized Cellulose Powder Reduces the Dose of Locally Applied Glucocorticoids in Patients with Allergic Rhinitis Xueyan Wang A139 New strategy for atopic dermatitis therapy with modulation of calcium ion channels Woo Kyung Kim, Yu Ran Nam, Joo Hyun Nam A140 Difference in the Systemic Bacterial Composition of Atopic Dermatitis Patients Compared to Healthy Subjects through Metagenomic Analysis of Urine Jung-Won Kim, Min-Hye Kim, Mina Rho, Yeon-Mi Kang, Kyung-Eun Yum, Hyeon-Il Choi, Jun-Pyo Choi, Han-Ki Park, Taek-Ki Min, Young Joo Cho, Bok-Yang Pyun, Yoon-Keun Kim A141 Occurrence and physiological function of immune complexes of food proteins and IgA in human saliva Hiroshi Narita, Junko Hirose, Kumiko Kizu, Ayu Matsunaga A142 Association between DNA hypomethylation at IL13 gene and allergic rhinitis in house dust mite-sensitized subjects Jingyun Li, Yuan Zhang, Luo Zhang A143 Effect of dietary methyl donors on asthma and atopy is modified by MTHFR polymorphism Yean Jung Choi, Hye Lim Shin, Song-I Yang, So-Yeon Lee, Sung-Ok Kwon, Young-Ho Jung, Ji-Won Kwon, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, Se-Young Oh, Ho-Jang Kwon, Eun Lee, Mi-Jin Kang, Soo-Jong Hong, Yun-Jeong Lee, Joonil Kim A144 The effect of TSLP in a murine model of allergic asthma Joon Young Choi, Ji Young Kang, Seok Chan Kim, Sei Won Kim, Seung Joon Kim, Young Kyoon Kim, Chin Kook Rhee, Hea Yon Lee, Hwa Young Lee, Sook Young Lee A145 Evaluation of Aspirin Hypersensitivity in Chronic Rhinosinusitis Patients Tae Kyung Koh, Sung Wan Kim, Kun Hee Lee, Chul Kwon, Joong-Saeng Jo, Sung-Hwa Dong, Young Seok Byun A146 Chronic cough without wheezing in young children as a manifestation of chronic sinusitis Charles Song A147 Expression of muscarinic receptors and effect of tiotropium bromide on chronic asthma according to age in a murine model Ji Young Kang, Hwa Young Lee, In Kyoung Kim, Sei Won Kim, Chin Kook Rhee, Seung Joon Kim, Seok Chan Kim, Sook Young Lee, Young Kyoon Kim, Soon Seog Kwon, Joon Young Choi A148 Discrimination between non-eosinophilic and eosinophilic chronic rhinosinusitis with nasal polyps Pona Park, Hong Ryul Jin, Dong-Kyu Kim, Dae Woo Kim A149 Significant reduction in allergic features in the offspring of mice supplemented with specific non-digestible oligosaccharides during lactation Astrid Hogenkamp A150 Allergenicity assessment of hydrolysed infant formula; A multicenter comparison of a mouse model and a Guinea pig model for cow’s milk allergy Leon Knippels, Betty C.a.m. Van Esch, Jolanda Van Bilsen, Prescilla V. Jeurink; Marjan Gros, Johan Garssen, Joost J Smit, Raymond H.H. Pieters A151 Clinical significance between the allergic test and serum eosinophil cationic protein Boo-Young Kim, Soo Whan Kim A152 Hydroclorothiazide-induced acute non-cardiogenic pulmonary edema Ramon Lleonart A153 A Synbiotic Mixture of Scgos/Lcfos and Bifidobacterium Breve M-16V Is Able to Restore the Delayed Colonization of Bifidobacterium Observed in C-Section Delivered Infants Christophe Lay, Kaouther Benamor, Chua Mei Chen, Jan Knol, Charmaine Chew, Voranush Chongsrisawat, Anne Goh, Wen Chin Chiang, Rajeshwar Rao, Surasith Chaithongwongwatthana, Nipon Khemapech A154 Atopic characteristics of patients with asthma-COPD overlap syndrome Ji Young Yhi, Sang-Heon Kim, Dong Won Park, Ji-Yong Moon, Tae Hyung Kim, Jang Won Sohn, Dong Ho Shin, Ho Joo Yoon, Seok Hyun Cho A155 Perceptions and practices of severe asthma and asthma-COPD overlap syndrome among specialists: A questionnaire survey Sang-Heon Kim, Ji-Yong Moon, Jae-Hyun Lee, Ga Young Ban, Sujeong Kim, Mi-Ae Kim, Joo-Hee Kim, Min-Hye Kim, Chan-Sun Park, Hyouk-Soo Kwon, Jae-Woo Kwon, Jae Woo Jung, Hye-Ryun Kang, Jong-Sook Park, Tae-Bum Kim, Heung Woo Park, You Sook Cho, Kwang-Ha Yoo, Yeon-Mok Oh A156 A case of surgical diagnosed eosinophilic enteritis with intussusception in adult patient Sang-Rok Lee A157 Reference values of total IgE in estonian children Kaja Julge, Maire Vasar, Tiia Voor, Tiina Rebane A158 A case of eosinophilic granulomatosis with polyangiitis accompanied by rapidly progressive glomerulonephritis Yu Jin Kim, Sang Min Lee, Shin Myung Kang, Sojeong Kim, Sun Young Kyung, Sung Hwan Jeong, Jeong-Woong Park, Hyunjung Hwang, Yong Han Seon, Sanghui Park, Sang Pyo Lee A159 Associations Between Infectious Diseases and Urticaria Marius Iordache A160 Sleep in infants in korea – finding of bisq survey Yeongsang Jeong, Sohee Eun, Byung Min Choi, Ji Tae Choung, Wonhee Seo A161 Increased Expression of Filaggrin, TSLP, Periostin, IL13 and IL-33 in Nasal Polyps Liang Zhang, Ruby Pawankar, Manabu Nonaka, Miyuki Hayashi, Shingo Yamanishi, Harumi Suzaki, Yasuhiko Itoh, So Watanabe, Hitome Kobayashi A162 Asymptomatic bacteruria increases the risk of edematous attacks in patients with hereditary angioedema due to C1 inhibitor deficency (C1-INH-HAE) Zsuzsanna Zotter, Henriette Farkas, Lilian Varga, Nora Veszeli, Eva Imreh, Gabor Kovacs, Marsel Nallbani A163 Gastric Erosions Cause Spontaneous Urticaria Independent of Helicobacter Pylori Semen Zheleznov, Galina Urzhumtseva, Natalia Petrova, Zhanna Sarsaniia, Nikolai Didkovskii, Torsten Zuberbier A164 The Effect of G2 Vaccine on the Gene Expression NKG2D and Receptor Presenting on the Surface of NK Cells in Peripheral Blood Nader Dashti Gerdabi, Ali Khodadadi, Zahra Abdoli, Mehri Ghafourian, Mohammad Ali Assarehzadegan, Khodayar Ghorban A165 Ethnic differences in lifetime prevalence and indoor environmental factors for childhood eczema Hyo-Bin Kim, Hui Zhou, Jeong Hee Kim, Rima Habre, Theresa Bastain, Frank Gilliland A166 A case of methazolamide-induced toxic epidermal necrolysis Jong-Wook Bae, Kyu-Hyung Han, Young-Koo Jee, Misoo Choi, Seung-Phil Hong, Seung-Hyun Kim A167 Inflammatory responses of human adipose-tissue derived stem cells to LPS and nanoparticles Hee-Kyoo Kim, Gil-Soon Choi, Jeonghoon Heo, Young-Ho Kim, Eun-Kee Park A168 Analysis of 71 Cashew Nut Oral Challenge Tests Takashi Inoue, Kiyotake Ogura, Noriyuki Yanagida, Hirotoshi Unno, Kenichi Nagakura, Tetsuharu Manabe, Tomoyuki Asaumi, Sakura Sato, Yu Okada, Motohiro Ebisawa A169 Fungal sensitization is associated with asthma exacerbation Min-Gu Kim, You Sook Cho, Tae-Bum Kim, Hee-Bom Moon, Jung-Hyun Kim, Hyo-Jung Kim, So-Young Park, Bomi Seo, Hyouk-Soo Kwon, Jaemoon Lee, Taehoon Lee A170 Individual therapeutic patient education and consultation in children with atopic dermatitis Hye-Soo Yoo, Jieun Kim, Inok Kim, Haejin Kim, Younhee Chang, Hae-Sim Park, Sooyoung Lee A171 Utility of Alpha-Lactalbumin Specific IgE Levels Using Immulite 2000 3gAllergy in Predicting Clinical Severity of Milk Allergy Kazuyo Kuzume, Munemitsu Koizumi, Koji Nishimura, Michiko Okamoto A172 Isoniazid/rifampicin-specific t-cell responses in patients with anti-tuberculosis –induced dress syndrome Seung-Hyun Kim, Young Min Ye, Gyu Young Hur, Hae-Sim Park, Sang-Heon Kim, Young-Koo Jee A173 Genetic biomarkers associated with aspirin-exacerbated respiratory disease (AERD) phenotype based on genome-wide association study Seung-Hyun Kim, Hyunna Choi, Young Min Ye, Hae-Sim Park A174 Assessment of ORAL drug provocation test in the diagnosis of NON-steroidal ANTI-inflammatory drugs hypersensitivity Bui VAN Khanh, Hieu Chi Chu, Nguyen Nhu Nguyet, Nguyen Hoang Phuong A175 Korean treatment guideline of atopic dermatitis Joo Young Roh, Hyun Jeong Kim, Jung Eun Kim, Bark-Lynn Lew, Kyung Ho Lee, Seung-Phil Hong, Yong Hyun Jang, Kui Young Park, Seong Jun Seo, Jung Min Bae, Eung Ho Choi, Ki Beom Suhr, Seung Chul Lee, Hyun-Chang Ko, Young Lip Park, Sang Wook Son, Young Jun Seo, Yang Won Lee, Sang Hyun Cho, Chun Wook Park A176 Systemic side reaction of subcutaneous immunotherapy(SCIT) for perennial allergic rhinitis Kun Hee Lee, Sung Wan Kim A177 Clinical baseline characteristics of Asian patients suffering from refractory chronic spontaneous urticaria (CSU) in three phase 3 omalizumab clinical trials Chia-Yu CHU, Derrick Aw, Young-Min Ye, Giovanni Bader, Fabrizio Dolfi, Nathalie Oliveira A178 A metagenomic approach through t-RFLP to the microbiome of asthma Jae Chol Choi, Jae Woo Jung, Hye-Ryun Kang, Kijeong Kim, Byoung Whui Choi A179 Clinical characteristics and ten-year trend of peripheral blood eosinophilia among health screening program recipients at a tertiary hospital of South Korea Jong Wook Shin, Jae Woo Jung, Jae Chol Choi, In Won Park, Byoung Whui Choi, Jae Yeol Kim A180 The prevalence of toxocariasis and diagnostic value of serologic tests in asymptomatic Korean adults Jin-Young Lee, Kyoung Won Ha, Yun-Jin Jeung, Sehyo Yune, Byung-Jae Lee, Dong-Chull Choi, Mi-Jung Oh, Young Hee Lim A181 Cutaneous Drug Hypersensitivity Reaction in Korean Children: An Analysis of KAERS Database on 2012-2013 Eui Jun Lee, Dongin Suh, Sung-Il Woo, Hwa Jin Cho, Eun Hee Chung, Soo Youn Chung A182 Comparison of clinical characteristics, quality of life and sleep in patients with allergic rhinitis when categorised as “sneezers and runners” and “blockers” Kamal Gera, Ashok Shah A183 Role of s-nitrosoglutathione reductase (GSNOR) in the murine strain differences of airway hyperresponsiveness Jin-Young Lee, Kyoung Won Ha, Mi-Jung Oh, Young Hee Lim, Sehyo Yune, Jae-Won Paeng, Mi-Jin Jang, Byung-Jae Lee, Dong-Chull Choi A184 Protection from airway bronchoconstriction by gsno Jin-Young Lee, Mi-Jin Jang, Jae-Won Paeng, Yun-Jin Jeung, Young Hee Lim, Mi-Jung Oh, Kyoung Won Ha, Byung-Jae Lee, Dong-Chull Choi, Sehyo Yune A185 Does EIA-targeted asthma treatment improve daily physical activity of children? Takahiro Ito A186 Wheezing as a clue to the diagnosis of cough variant asthma and nonasthmatic eosinophilic bronchitis Jihye Kim, Jin-Young Lee, Sehyo Yune, Byung-Jae Lee, Dong-Chull Choi, Mi-Jin Jang, Jae-Won Paeng, Young Eun Kim, Young Nam Kim, Yongseok Lee A187 Antagonism of microRNA-21 suppressed the airway inflammation in a mouse model of bronchial asthma Hwa Young Lee, Sook Young Lee, Soon Seog Kwon, Young Kyoon Kim, Chin Kook Rhee, Sei Won Kim, Hea Yon Lee, Joon Young Choi, In Kyoung Kim A188 Chlorhexidine anaphylaxis: A report of two cases Jose Antonio Navarro, Maria Ascension Aranzabal, Alejandro Joral, Susana Lizarza, Miguel Echenagusia, EVA Maria Lasa A189 Effects of Particulate Matter on Respiratory Allergic Diseases Considering Meteorological Factors in Busan, Korea Eun-Jung Jo, Sun-Mi Jang, Seung-Eon Song, Hae-Jung Na, Chang-Hoon Kim, Woo-Seop Lee, Hye-Kyung Park A190 Clinical characteristics of neutrophilic asthma Sachiko Miyauchi, Yoshitaka Uchida, Tomoyuki Soma, Susumu Yamazaki, Toru Noguchi, Takehito Kobayashi, Kazuyuki Nakagome, Makoto Nagata A191 Current Practice of Infants and Children with Acute Urticaria at a Single Wide Regional Emergency Medical Center Hea Lin Oh, Do Kyun Kim, Dongin Suh, Young Yull Koh A192 Discordance between sputum eosinophilia and exhaled nitric oxide Sehyo Yune, Jin-Young Lee, Byung-Jae Lee, Dong-Chull Choi, Jae-Won Paeng, Mi-Jin Jang, Jihye Kim, Young Nam Kim A193 Association between genetic polymorphisms of costimulatory molecules and antituberculosis drugs induced hepatitis Sang-Heon Kim, Sang-Hoon Kim, Jang Won Sohn, Ho Joo Yoon, Dong Ho Shin, Jae Hyung Lee, Byoung Hoon Lee, Youn-Seup Kim, Jae-Seuk Park, Young-Koo Jee A194 The prevalence of gastroesophageal reflux disease in chronic unexplained cough Sehyo Yune, Jin-Young Lee, Jae-Won Paeng, Mi-Jin Jang, Dong-Chull Choi, Byung-Jae Lee, Yongseok Lee, Young Eun Kim A195 Risk Factors of Allergic Rhinitis in Preschool Children and Clinical Utility of Feno Jisun Yoon A196 Relationship between serum 25-hydroxyvitamin d and asthma exacerbation severity in children Yong Feng, Li Zhang, Xuxu Cai A197 Usefulness of Specific IgE Antibody Levels to Wheat, Gluten and Ï-5 Gliadin for Wheat Allergy in Korean Children Jong-Seo Yoon, Kyunguk Jeong, Hye-Soo Yoo, Sooyoung Lee, Sooyoung Lee A198 Neutralization of stratum corneum accelerates the progress from atopic dermatitis to asthma-like lesion in flaky tail mice treated by house dust mite allergen Hae-Jin Lee, Noo Ri Lee, Bo-Kyung Kim, Minyoung Jung, Dong Hye Kim, Catharina S. Moniaga, Kenji Kabashima, Eung Ho Choi A199 Trends in oral food challenges in Japan: A six-year prospective study Noriyuki Yanagida, Sakura Sato, Chizuko Sugizaki, Motohiro Ebisawa A200 The Gut Microbiome in the Food Allergic Host Jamie Kiehm, Punita Ponda, Sherry Farzan, Jared Weiss, Claudia Elera, Catherine Destio, Cristina Sison, Annette Lee A201 Cord blood cytokines and maternal environmental exposure during pregnancy Soo Hyun Ri, Chang Hoon Lim A202 Rupatadine pharmacokinetics in Japanese healthy volunteers after single and repeated oral doses of 10, 20 and 40 mg Iñaki Izquierdo Pulido, Jorg Taubel, Georg Ferber, Eva Santamaria Masdeu A203 A safe and effective method to desensitize patients with wheat allergy Alireza Khayatzadeh, Masoud Movahedi, Motohiro Ebisawa, Mohammad Gharagozlou A204 RNA Binding Protein Hur Regulates CD4+ T Cell Differentiation and Is Required for Allergic Airway Inflammation and Normal IL-2 Homeostasis Ulus Atasoy, Patsharaporn Techasintana, Matt Gubin, Jacqueline Glascock, Suzanne Ridenhour, Joseph Magee A205 Time Trends in the Epidemiology of Recurrent Wheezing in Infants from South America Nelson Rosario Filho; Herberto Jose Chong Neto, Gustavo Falbo Wandalsen, Ana Caroline Dela Bianca, Carolina Aranda, Dirceu Sole, Javier Mallol, Luis Garcia-Marcos, Luis Garcia-Marcos A206 Successful Cyclophosphamide Desensitization in a Pediatric Patient with Systemic Lupus Erythematosus Jennifer Toh, Yoomie Lee, Joyce Huang, Elina Jerschow, Jenny Shliozberg A207 The Fatty Acid Binding Protein Der p 13 Is a Minor House Dust Mite Allergen Able to Activate Innate Immunity Pattraporn Satitsuksanoa, Narissara Suratannon, Jongkonnee Wongpiyabovorn, Pantipa Chatchatee, Kiat Ruxrungtham, Alain Jacquet A208 Epidemiology of Stevens-Johnson Syndrome and Toxic Epidemal Necrolysis: An Administrative Database Study Min Suk Yang; Jin Yong Lee, Ja Yeun Kim, Han-Ki Park, Ju-Young Kim, Woo-Jung Song, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Sang-Heon Cho, Kyung-up Min, Chang-Han Park, Suk-Il Chang, Sook-Hee Song A209 Regional Differences of Vitamin D and Food-Induced Anaphylaxis in Korea Si-Heon Kim, Gil-Soon Choi, Su-Chin Kim, Ji Hye Kim, Ga Young Ban, Yoo Seob Shin, Hae-Sim Park, Young Min Ye A210 Triggering Factors of Atopic Dermatitis By Severity Yoon Ha Hwang A211 Clinical Features of Adverse Drug Reactions of Monoclonal Antibodies in Korea Da Woon Sim, Kyung Hee Park, Kyung Hee Park, Hye Jung Park, Hye Jung Park, Jung-Won Park, Jung-Won Park, Jae-Hyun Lee, Jae-Hyun Lee A212 Food Allergy with Eczema Is Associated with Reduced Growth in the First Four Years of Life Katrina Allen, Cara Beck, Jennifer Koplin, Melanie Matheson, Mimi Tang, Anne-Louise Ponsonby, Lyle Gurrin, Shyamali Dharmage, Melissa Wake, Vicki Mcwilliam A213 The Preliminary Study on Clinical Efficacy and Impact Factors of One Year’s Dust Mite Specific Immunotherapy in Allergic Asthma and Rhinitis Children Sensitized to Dust Mite Xiaoying Liu, Jing Wang, Li Xiang, Qun Wang A214 Lipopolysaccharide Signaling through Toll- like Receptor 4 Could be Augmented By Dermatophagoides Farinae in the Human Middle Ear Epithelial Cell Ji-Eun Lee, Dong-Young Kim, Chae-Seo Rhee, Chae-Seo Rhee A215 Drug Allergy in Pregnant Adolescents: Relation with Familial and Personal Atopy, and Substances Use Francisco Vazquez-Nava A216 Patients and Physicians Concept of Well-Controlled Asthma: Findings from Realise Asia Sang-Heon Cho, Jaewon Jeong, Diahn-Warng Perng, David Price, Glenn Neira, Jiangtao Lin A217 The Role of Vasoactive Intestinal Peptide in the Pathophysiology of Acute Asthma Olga Semernik A218 Comparison of Serum Cytokine Levels According to the Severity in Atopic Dermatitis Ha-Su Kim, Jin-a Jung, Ji-in Jung A219 The Different Influence on the Regulatory T Cell Response Between Subcutanous Immnuotherapy(SCIT) and Sublingual Immunotherapy(SLIT) in Children with Asthma Qing Miao, Li Xiang A220 Asthma State of Affairs in Asia: Seeing through Physicians’ and Patients’ Lenses Sang-Heon Cho, Jaewon Jeong, Diahn-Warng Perng, Jiangtao Lin, David Price A221 Identification of Aspirin Exacerbated Respiratory Disease (AERD) Phenotypes Using Two Step Cluster Analysis Hyun Young Lee, Hae-Sim Park, Young Min Ye, Su Chin Kim A222 Dusty Air Pollution Are Associated with an Increase Risk of Allergic Diseases in General Population Shokrollah Farrokhi, Mohammadkazem Gheiby A223 A Genome-Wide Association Study of Antituberculosis Drugs-Induced Hepatitis Sang-Heon Kim; Heung Woo Park, Sang-Hoon Kim, Young-Koo Jee A224 The Role of peroxiredoxin6 of Bronchial Epithelial Cells in Regulating Mitochondrial Function Under Oxidative Stress By Translocation to Outside Mitochondrial Membrane Sunjoo Park, Keun Ai Moon, Hyouk-Soo Kwon, Tae-Bum Kim, You Sook Cho, Hee-Bom Moon, Kyoung Young Lee, Gyong Hwa Hong, Eun Hee Ha A225 Toxic and Adjuvant Effects of 3 Types of Silica Nanoparticles on Airway System Heejae Han, Hye Jung Park, Yoon Hee Park, Yoon-Jo Kim, Kangtaek Lee, Jung-Won Park, Jae-Hyun Lee A226 Procedure for Diagnostic and Selection of Immunotherapy Method for Children with Different Immunopathogenetic Phenotypes of Atopic Dermatitis Tatiana Slavyanskaya, Vladislava Derkach A227 Prediction of the Success of Our Desensitization Protocol with Symptoms and Results of a Skin Prick Test in Patients with Hypersensitivity to Platinum-Based Chemotherapy Hye Jung Park, Chein-Soo Hong, Jae-Hyun Lee, Jae-Hyun Lee, Sungryeol KIM, Sungryeol KIM, Kyung Hee Park, Kyung Hee Park, Choong-Kun Lee, Beodeul Kang, Seung-Hoon Beom, Sang Joon Shin, Minku Jung, Jung-Won Park, Jung-Won Park A228 Anti-Allergic Effect of Intralymphatic Injection of OVA-Flagelin Mixture in Mouse Model of Allergic Rhinitis Eun-Hee Kim, Ji-Hye Kim, Ji-Hun Mo, Young-Jun Chung A229 Serum Periostin Level Is Higher in Respiratory Type of NSAID Hypersensitivity Than Cutaneous Type Mi-Ae Kim, Hae-Sim Park, Moon Gyeong Yoon, Young-Soo Lee, Ji Hye Kim, Ga Young Ban, Hye-Soo Yoo, Yoo Seob Shin, Young Min Ye, Dong-Ho Nahm A230 A Retrospective Analysis of Allergy Blood Testing in Beijing Children’s Hospital in the Year of 2013: A Single-Center Research Qing Miao, Li Xiang A231 Role of Nrf2 in the Allergic Airway Inflammation Differ Between BALB/c and C57BL/6 Mice Ying-Ji Li, Takako Shimizu, Hirofumi Inagaki, Yukiyo Hirata, Hajime Takizawa, Arata Azuma, Masayuki Yamamoto, Tomoyuki Kawada A232 Effect of Human Mesenchymal Stem Cell on Neutrophilic Asthma Model Min-Gu Kim, Gyong Hwa Hong, Kyoung Young Lee, Eun Hee Ha, Keun Ai Moon, Sunjoo Park, Hyouk-Soo Kwon, Tae-Bum Kim, Hee-Bom Moon, You Sook Cho, Jung-Hyun Kim, Hyo-Jung Kim, So-Young Park, Bomi Seo A233 Immunomodulatory Effect of Tonsil Derived Mesenchymal Stem Cells in a Mouse Model of Allergic Rhinitis Ji-Hye Kim, Ramachandran Samivel, Eun-Hee Kim, Young-Jun Chung, Ji-Hun Mo A234 Alternative Therapy Such As Yoga May be a Low Cost Tool for Improving the Quality of Life of Patient’s with Allergic Rhinitis and Asthma Soumya M. S., G. Inbaraj, R. Chellaa, Ruby Pawankar A235 Substantial Impairment of the Quality of Life in Adult Patients with Chronic Urticaria Wonsun Choi, Hae-Sim Park, Young Min Ye, Ji Hye Kim, Ga Young Ban, Yoo-Seob Shin A236 Dietary Galacto-Oligosaccharides Reduce Airway Eosinophilia and Enhance the Th2 Suppressive Effect of Budesonide in House Dust Mite-Induced Asthma in Mice Saskia Braber, Kim Verheijden, Aletta Kraneveld, Johan Garssen, Linette Willemsen, Gert Folkerts A237 Production and Characterization of Recombinant Periplaneta americana Allergens for Component Resolved Diagnosis Stephanie Eichhorn, Fatima Ferreira, Isabel Pablos, Bianca Kastner, Bettina Schweidler, Sabrina Wildner, Peter Briza, Jung-Won Park, Naveen Arora, Stefan Vieths, Gabriele Gadermaier A238 Assessment of Characteristics of Itch in Patients with Hand Eczema Sung-Min Park, Won-Ku Lee, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Hoon-Soo Kim, Margaret Song, Hyun-Chang Ko, Moon-Bum Kim, Byung Soo Kim A239 The Hidden Culprit: A Case of Repeated Anaphylaxis from Cremophor Hypersensitivity. Young Nam Kim, Sehyo Yune, Jin-Young Lee, Jihye Kim, Young Eun Kim, Jae-Won Paeng, Mi-Jin Jang, Dong-Chull Choi, Byung-Jae Lee, Yongseok Lee A240 Spectrum of Anaphylaxis in Children and Adults at Emergency Departments in Singapore Si Hui Goh, Bee Wah Lee, Jian Yi Soh A241 Improved Quality of Life through an Integrated Health Care Service for Children with Atopic Dermatitis Hyungoo Kang; Hyunhee Kim; Hye-Yung Yum A242 Criteria Combining Autologous Serum Skin Test and Clusterin for Predicting Antihistamine-Refractoriness in Patients with Chronic Spontaneous Urticaria Young Min Ye; Hae-Sim Park; Ga-Young Ban; Ji Hye Kim; Yoo Seob Shin A243 Urinary Leukotriene E4 Levels in Wheezing Infants Takumi Takizawa, Masahiko Tabata, Akira Aizawa, Hisako Yagi, Yutaka Nishida, Hirokazu Arakawa, Akihiro Morikawa, Solongo Orosoo A244 Allergic Sensitization to Whey in Mice Is Facilitated By the Mycotoxin Deoxynivalenol (DON) Saskia Braber, Marianne Bol-Schoenmakers, Peyman Akbari, Prescilla V. Jeurink, Prescilla V. Jeurink, Priscilla De Graaff, Joost J. Smit, Betty C. A. M. Van Esch, Johan Garssen, Johan Garssen, Johanna Fink-Gremmels, Raymond H. H. Pieters A245 How to Define Chronic Cough: Based on a Systematic Review of the Epidemiological Literature Gun-Woo Kim, Eun-Jung Jo, Sujeong Kim, Woo-Jung Song, Yoon-Seok Chang, Shoaib Faruqi, Ju-Young Kim, Mingyu Kang, Min-Hye Kim, Jana Plevkova, Heung Woo Park, Sang-Heon Cho, Alyn Morice, So-Hee Lee, Sun-Sin Kim, Seoung-Eun Lee A246 Asko Study: Comparison of Behavior and Habits in Diagnosis and Treatment of Adult Asthma and COPD Patients Bilun Gemicioglu, Zeynep Misirligil, Arif Hikmet Cimrin, Hakan Gunen, Tevfik Ozlu, Aykut Cilli, Levent Akyildiz, Hasan Bayram, Esra Uzaslan, Oznur Abadoglu, Mecit Suerdem A247 Changes in Pulmonary Function in the Treatment of Obesity in Children Keigo Kainuma A248 Changes of Feno and Nasal Feno Levels after Treatment in Pediatric Allergic Rhinitis Hyun-a Kim, Ha-Su Kim, Woo Yong Bae, Jin-a Jung A249 Prevalence of Vitamin D Deficiency in Exclusively Breastfed Infants in Kenya Rose Kamenwa, William Macharia, Nusrat Said A250 In-Vitro Screening of Atopy in the Indian Population: Are Current Methods Adequate, Keeping Local IgE Seroprevalence for Common Food & Inhalant Allergens in Mind? Vidya Nerurkar, Meenal Patel, Simi Bhatia A251 Usefulness of House Dust Mites Nasal Provocation Test in Asthma Inseon S Choi, Soo-Jeong Kim, Joo-Min Won, Myeong-Soo Park A252 Biomarker-Based Treatment Option for Preschool Children with Recurrent Wheeze Mizuho Nagao A253 Anti-Tuberculosis Drugs-Induced Liver Injury in Patients with Connective Tissue Diseases Dong Won Park, Jang Won Sohn, Ji Young Yhi, Ji-Yong Moon, Sang-Heon Kim, Tae Hyung Kim, Dong Ho Shin, Ho Joo Yoon A254 Ocular Symptoms of Cedar Pollinosis in Otolaryngology Patients Yukiyoshi Hyo A255 The Clinical Characteristics of Adverse Drug Reactions Reported in a Regional University Hospital for 6 Years and the Suggestions for the Reporting System Jaechun Lee, Su Hee Kim, Eunkyoung Lee A256 Changes in Skin Prick Test Results over 3 Years in School-Aged Children Hahn Jin Jung, Jaehyun Lim, Seung-No Hong, Doo Hee Han, Chae-Seo Rhee A257 The Analysis of Risk Factors and Features of Food Allergy in Korean Children: Nationwide Cross-Sectional Survey Kun Song Lee A258 A Sequential Indirect-Direct Bronchial Provocation Test for Diagnosis of Asthma: A Pilot Study Jaechun Lee, Sun Young Yang, Mi Young Ahn, Jong Hoo Lee, Jasmina Golez A259 Association of VDR and CYP2R1 Polymorphisms with Persistent Allergic Rhinitis in a Han Chinese Population Hui-Qin Tian, Lei Cheng, Xin-Yuan Chen A260 Associations of Metabolic Syndrome with Asthma and Atopy in Korean Adults Ji-Yong Moon, Sang-Heon Kim, Tae Hyung Kim, Ji Young Yhi, Ho Joo Yoon, Jang Won Sohn, Dong Ho Shin, Dong Won Park A261 Clinical Manifestation and Treatment Outcome of Eosinophilic Gastroenteritis in Korean Children Won Im Cho, Jong Sub Choi, Dongin Suh, Gyeong Hoon Kang, Jin Soo Moon, Jae Sung Ko, Kyung Jae Lee, Shin Jie Choi A262 The Sensitization Model and Correlation of Bermuda and Timothy Grass Pollen Allergen in Allergic Patients in Southern China Wenting Luo, Baoqing Sun A263 A Pilot Study on the Outcomes of Respiratory Allergic Diseases at Pre-School Age in Chinese Infants with Atopic Dermatitis Qi Gao, Li Xiang, Kunling Shen A264 Activation of Toll like Receptor 1 and 6 By House Dust Mite Enhances the Expression of Tight Junction Protein in Epidermal Keratinocytes Yong Hyun Jang A265 Pollen Exposure in a Mobile Exposure Chamber: Comparing Real-Life Symptoms with Exposure Symptoms Karl-Christian Bergmann, Torsten Sehlinger, Georg Bölke, Uwe Berger, Torsten Zuberbier A266 Retrospective Analysis of the Incidence of Allergy in Patients with Contact Eczema Joanna Kolodziejczyk, Milena Wojciechowska, Anna Hnatyszyn-Dzikowska, Micha Chojnacki, Zbigniew Bartuzi A267 Effect of Fungal Sensitization in Patients with Severe Asthma Katsunori Masaki, Koichi Fukunaga, Takashi Kamatani, Kengo Ohtsuka, Takae Tanosaki, Masako Matsusaka, Takao Mochimaru, Hiroki Kabata, Soichiro Ueda, Yusuke Suzuki, Katsuhiko Kamei, Koichiro Asano, Tomoko Betsuyaku A268 SCIg Patient Preference Pump Versus Push Karlee Trafford A269 Fixed Drug Eruption Induced By Ornidazole and Diclofenac Ismet Bulut, Zeynep Ferhan Ozseker A270 Transepidermal Water Loss Measurement during Infancy Can Predict the Subsequent Development of Atopic Dermatitis Kenta Horimukai, Hideaki Morita, Masami Narita, Hironori Niizeki, Kenji Matsumoto, Yukihiro Ohya, Hirohisa Saito, Shigenori Kabashima, Mai Kondo, Eisuke Inoue A271 Inhalant Allergens on Soft Toys: A Literature Review Robert Siebers, Francis FS Wu A272 Fractional Exhaled Nitric Oxide in Elderly Asthmatics Robert Siebers, Francis FS Wu, Ming-Hui Ting, Hung-En Laio, Tsung-Huai Kuo, Pei-Yuan Lee A273 Dye and Preservative Challenge in Meal-Associated Urticaria and Angioedema: A Low-Yield Diagnostic Maneuver Daniel Eugene Maddox A274 The Changes of Allergic Sensitization with Age in Children with Allergic Rhinitis Gwanghui RyuHyo Yeol Kim, Hun-Jong Dhong, Sang Duk Hong, Seung-Kyu Chung A275 Component-Specific IgE and IgG4 Levels in Milk Allergy Children Tolerated Baked Milk Products Osamu Higuchi, Yu-Ichi Adachi, Toshiko Itazawa, Yoko Adachi, Miki Hamamichi, Motokazu Nakabayashi, Yasunori Ito, Takuya Wada, Gyoukei Murakami, Miki Takao, Junko Yamamoto A276 Serum Surfactant Protein(SP)-D Level: A Potential Biomarker for Aspirin-Exacerbated Respiratory Disease Hyun Jung Jin, Moon Gyeong Yoon, Young Min Ye, Yoo-Seob Shin, Seung-Hyun Kim, Hae-Sim Park A277 Clinical Characteristics of Anaphylaxis in Korean Children Taek-Ki Min, Bok-Yang Pyun, So-Yeon Lee, Hyun Hee Kim, Gwang-Cheon Jang, Jinho Yu, Dongin Suh, Sooyoung Lee, Yong Mean Park, Jeong Hee Kim, Hye-Yung Yum, Kyung Won Kim, Hyeon-Jong Yang, Kangmo Ahn, Ji-Won Kwon, Myung Hyun Sohn, Hae Ran Lee, Jung Hyun Kwon, Kyu-Earn Kim, Soo-Jong Hong A278 Immunological Changes Induced By Intramuscular Injections of Autolologous Immunoglobulin in Patients with Severe Atopic Dermatitis Su-Mi Cho A279 Identification of Subtypes in Subjects with Mild to Moderate Airflow Limitation and Their Clinical and Socioeconomic Implications Jin Hwa Lee, Chin Kook Rhee, Hye Yun Park, Woo Jin Kim, Yong Bum Park, Kwang-Ha Yoo A280 Cephalosporin-Induced Dress (Drug Rash with Eosinophilia and Systemic Symptoms) Syndrome in a 7-Year-Old Boy Heejeong Kang, Hyeon-Jong Yang, Taek-Ki Min, Bok-Yang Pyun A281 Maternal Depression Is Associated with Children’s Asthma : An Analysis of the Fifth Korea National Health and Nutrition Examination Survey (2010-2012) Lee Ju Suk, Cheol Hong Kim A282 Increased Length of Hospitalization Associated with Infiltration on Chest Radiography in Pediatric Asthma Patients Jung Hyun Kwon, Sang Hyun Lee, Wonhee Seo A283 A Case of 16-Year-Old Boy with Smoking-Induced Acute Eosinophilic Pneumonia Kang-in Kim, Young Cheon Park, Hyeon-Jong Yang, Taek-Ki Min; Bok-Yang Pyun A284 A Case of Pranlukast Induced Anaphylactic Shock Sujeong Kim, Sun Jin, Jong-Myung Lee, Hye-Jin Jung, Jung-Wha Park A285 Comparison of Asthma-Related Outcomes Between Metabolically Healthy Obese and Metabolically Unhealthy Obese Asthma Patients Hyo-Jung Kim, Tae-Bum Kim, You Sook Cho, Hee-Bom Moon, Hyouk-Soo Kwon, So Young Park, So-Young Park, Jung-Hyun Kim, Bomi Seo, Min-Gu Kim, Youn Yee Kim A286 Rick Factors Associated with Longer Length of Stay in Infants Hospitalized with Respiratory Syncytial Virus Bronchiolitis Yena Lee, Taek-Ki Min, Hyeon-Jong Yang, Bok-Yang Pyun, Suk Hee Han, Suyeon Park, Jeongho Lee, Won-Ho Hahn A287 Urinary Excretion of 9α, 11Î(2)-Prostaglandin F(2) and Leukotriene E(4) in Patients with Exercise-Induced Bronchoconstriction Youhoon Jeon, Joo-Hee Kim, Tae-Rim Shin, Cheol-Hong Kim, In-Gyu Hyun, Jeong-Hee Choi A288 The Aeroallergen Sensitization Pattern and Effect on Airway Hyperresponsiveness in Busan, Korea Sun-Mi Jang, Hae-Jung Na, Seung-Eon Song, Hye-Kyung Park, Eun-Jung Jo A289 Multicenter Questionnaires on Current Management of Atopic Dermatitis Among Korean Patients and Caregivers Dong Hun Lee, Jin-Young Lee, Yang Park, Jae-Won Oh, Mi Hee Lee, Soo-Jong Hong, Soo-Jong Hong, So-Yeon Lee, Joon Soo Park, Dong-Ho Nahm, Hye-Yung Yum, Hye-Yung Yum A290 Der p 1, Der p 2 and Der p 10 IgE Reactivities in Allergic Rhinitis Patients in Korea Kyu Young, Dong-Young Kim A291 De-Labeling Beta-Lactam Hypersensitivity: An Experience from a Tertiary Care Hospital in Thailand Sirinoot Palapinyo; Jettanong Klaewsongkram A292 Sonic Hedgehog Signaling: Evidence for Its Protective Role in Endotoxin Induced Acute Lung Injury Mouse Model Xing Chen, Yuting Jin, Xiaoming Hou, Fengqin Liu, Chunyan Guo, Yulin Wang A293 Analyses of the Factors behind the Negative Attitudes Toward the Administration of Adrenaline Auto-Injectors in School Settings Ikuo Okafuji, Yuya Tanaka, Shegeyuki Narabayashi, Satoru Tsuruta A294 Low Vitamin D Levels Are Related to High House Dust Mite Sensitization in Patients with Severe Atopic Dermatitis Yong Hyun Jang A295 Appendicular Skeletal Muscle Mass Index: A Potential Predictor of Skeletal Muscle Abnormality According to the Severity Airflow Limitation of COPD Jun-Hong Ahn, Dong-Won Lee, Jin Hong Chung, Hyun Jung Jin, Min-Su Sohn A296 Etiology and Clinical Feature of Oral Allergy Syndrome in Children Young a Park, Kyunguk Jeong, Yoon Hee Kim, In Suk Sol, Seo Hee Yoon, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Sooyoung Lee A297 Traffic-Related Pollution Levels and Poorly Controlled Asthma in Adults Ho Kim, Ja Yeun Kim A298 Anaphylaxis in Korean Children, 2009-2013 : Triggers of Anaphylaxis By Age Groups So-Yeon Lee, Taek-Ki Min, Tae-Won Song, Kangmo Ahn, Jihyun Kim, Gwang-Cheon Jang, Hyeon-Jong Yang, Bok-Yang Pyun, Ji-Won Kwon, Myung Hyun Sohn, Kyu-Earn Kim, Jinho Yu, Soo-Jong Hong, Jung-Hyun Kwon, Sung-Won Kim, Sooyoung Lee, Woo Kyung Kim, Hyung Young Kim, Hye-Young Kim, Youhoon Jeon A299 Maternal Allergy Is Associated with Acute Bronchiolitis Severity in Infant Chang Hoon Lim, Yeongsang Jeong, Su Jung Kim A300 Evaluation of Inflammatory Mediator Profiles in Sputum of Asthmatics As an Endotype for Refractory Asthma Hun Soo Chang, Jeong-Seok Heo, Da-Jeong Bae, Jong-Uk Lee, Ji-Na Kim, Chang-Gi Min, Hyun Ji Song, Jong-Sook Park, Soo Hyun Kim, Choon-Sik Park A301 Autophagy Is Associated with the Severity of Asthma in an Ovalbumin-Specific Mouse Model of Allergic Asthma Jing-Nan Liu, Youngwoo Choi, Yoo Seob Shin, Hae-Sim Park A302 Interleukin-9 and Interleukin-33 Levels in Children with Asthma Nima Rezaei, Sedigheh Bahrami Mahneh, Arezou Rezaei, Maryam Sadr, Masoud Movahedi A303 Pediatric Anaphylaxis at a University Hospital in Cheonan, Korea, 2013~2014 Jun Seak Gang, Joon Soo Park, Seung Soo Kim, Hyun Ho Bang, Kyeong Bae Park, Hye Sun Kim, Tae Ho Kim, Young Hwangbo, Hyun Jung Lee, Gyeong Hee Yoo, Young Chang Kim A304 Initial Antigen-Specific IgE Levels Predict Clinical Outcome of Rush Oral Immunotherapy for Food Anaphylaxis Sakura Sato, Noriyuki Yanagida, Motohiro Ebisawa A305 ABCC4 gene Polymorphism Is Associated with High Periostin Levels in Asthmatic Patients Sailesh Palikhe, Hae-Sim Park, Seung-Hyun Kim, Ri-Yeon Kim, Eun-Mi Yang A306 The Role of Clinical Phenotype and Allergen Sensitization at 2 Years As Predictors of Atopic Disorders at 5 Years Li Yuan Gabriella Nadine Lee, Marion Aw, Marion Aw, Bee Wah Lee, Bee Wah Lee, Evelyn Xiu Ling Loo, Yiong Huak Chan, Lynette Shek, Lynette Shek, I-Chun Kuo, I-Chun Kuo, Phaik Ling Quah, Phaik Ling Quah, Genevieve Llanora, Gerez Irvin A307 The Effect of Korean Red Ginseng (KRG) on Rhinovirus Infection in Human Nasal Epithelial Cells Joo Hyun Jung, Il Gyu Kang, Seon Tae Kim, Hyoungmin Park A308 The Effect of Korean Red Ginseng on the Symptoms and Allergic Inflammation in Patients with Allergic Rhinitis Seon Tae Kim, Joo Hyun Jung, Il Gyu Kang, Hyoungmin Park, Kwang-Pil Ko A309 Validation of the Newly Developed Multiple Allergen Simultaneous Test in Korea Jungsoo Lee, Howard Chu, Hemin Lee, Jung U Shin, Chang Ook Park, Kwang Hoon Lee, Kwang Hoon Lee, Hong Kyu Kang A310 Assessment of Symptoms Severities of Allergic Rhinitis Patients Sensitive to Multiple Allergens in Skin Prick Test Dong Chang Lee, Geun Jeon Kim, Jae Hyung Hwang, Jin Bu Ha, Su Hee Jeong A311 Diurnal Temperature Range and Emergency Department Visits for Asthma in Korea 6 Cities Ho Kim, Shinha Hwang, Whahee Lee A312 Mannan-Binding Lectin Serum Levels in Atopic Mongolian Adults Enkhbayar Bazarsad, Logii Narantsetseg, Munkhbayarlakh Sonomjamts A313 Prevalence of Doctor Diagnosed Atopic Eczema, during 2003-2014 in KOREA ; Using Big Data of 48.1 Million South Korean Health-Care Records Gwang-Cheon Jang, Hyun-Hee Lee, Chang-Jong Lee, Huynsun Lim A314 Association of Recurrent Wheeze with Lung Function and Airway Inflammation in Preschool Children Ji-Eun Soh, Dae-Jin Song, Ji-Won Kwon, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, So-Yeon Lee, Gwang-Cheon Jang, Woo Kyung Kim, Young-Ho Jung, Soo-Jong Hong, Jung Yeon Shim A315 Mannan-Binding Lectin Serum Levels in Healthy Mongolian Adults Enkhbayar Bazarsad, Logii Narantsetseg, Munkhbayarlakh Sonomjamts A316 Rotanebuliser Prabhakarrao Pv, Ranjitha Nadendla A317 The Level of Serum Interleukin 13 and Interleukin 17A and Its Effect Factors in Children with Asthma Juan Fang, Jing Zhao A318 Is Vitamin D Insufficiency Also Involved in Childhood Asthma in South Korea? Dae-Jin Song, Sungchul Seo, Young Yoo, Yu-Ri Kim, Ji Tae Choung, Jee Hoo Lee A319 Collection of Nasal Secretions for Measurement of Local IgE: A Quest for the Best Method Margot Berings, Natalie De Ruyck, Claus Bachert, Philippe Gevaert, Gabriële Holtappels A320 The Role of Claudin 5 in a Murine Model of Asthma Pureun-Haneul Lee, Byeong-Gon Kim, Choon-Sik Park, George D Leikauf, An-Soo Jang A321 Claudin-4 in a Murine Model of Asthma: Modulation By Acrolein, a Highly Reactive Unsaturated Aldehyde Byeong-Gon Kim, Pureun-Haneul Lee, Choon-Sik Park, An-Soo Jang A322 Efficacy and Safety of Sublingual Immunotherapy in House Dust Mite Sensitized Children with Allergic Rhinitis Yang Park A323 The Association of Vitamine D Deficiency and Skeletal Muscle Dysfunction in Chronic Airway Disease Min-Su Sohn, Hyun Jung Jin, Dong-Won Lee, Jun-Hong Ahn, Jin Hong Chung A324 Bacteria Derived Extracellular Vesicles in Indoor Dust Is Closely Associated with Airway Disease and Lung Cancer: Analysis of Indoor Dust’s Microbiome and IgG Sensitization of Indoor Bacteria Derived Extracellular Vesicles Sae-in Kim, Han-Ki Park, Do-Yeon Kim, Mina Rho, Jun-Pyo Choi, Yoon-Keun Kim A325 Clinical Care Program for Childhood Asthma (CCP-Childhood Asthma); A Multidisciplinary Team Care at Samitivej International Children’s Hospital Wasu Kamchaisatian, Thitikul Hiranras, Surinda Wongpun, Phornthip Chiraphorn, Anupan Tantachun, Wannipa Wongrassamee, Planee Vatanasurkitt, Naratip Somboonkul, Nattipat Juthacharoenwong, Surangkana Techapaitoon, Montri Tuchinda A326 Continuous B Cell Stimulation with CD40 Ligand Induce IgE Isotype Switching Jae Ho Lee, Sejin An A327 Effects of Interleukin-9 on Allergen-Specific Immunotherapy in a Mouse Model of Allergic Rhinitis Ji-Hyeon Shin, Soo Whan Kim, Si Won Kim, Jun Myung Kang, Boo-Young Kim, Byung-Guk Kim A328 Usefulness of Exhaled Nitric Oxide for Evaluating Wheeze and Airway Hyperresponsiveness in Preschool Children Jung-Won Lee, Ji-Won Kwon, Woo Kyung Kim, Hyung Young Kim, Hyo-Bin Kim, Ju-Hee Seo, So-Yeon Lee, Gwang-Cheon Jang, Young-Ho Jung, Soo-Jong Hong, Byoung-Ju Kim, Dae-Jin Song, Jung Yeon Shim A329 Systemic Cyclosporine Treatment in Hand Eczema Patients Kyung Ho Kim A330 Lipid Profiles and Adipokines in Korean Children with Atopic Dermatitis Young Yoo, Won Suck Yoon, Sungchul Seo, In Soon Kang, Jae Won Choi, Hye-Young Lim, Ji Tae Choung A331 Validation of Montelukast and Levocetirizine Combination Tablet Versus Individual Tablets in the Treatment of Moderate to Severe Persistent Allergic Rhinitis Among Adult Filipinos Seen at the Philippine General Hospital-Outpatient Department Michelle Buela A332 Efficacy of Makyokansekito on Treatment of Wheezing Lower Respiratory Tract Infection in Children: A Retrospective Study of 68 Patients Koji Nishimura A333 Serum Eosinophilia and Total IgE Are Associated with the Risk of Allergic Sensitization and Allergic Symptoms in Two Years Follow-up, Respectively Sang Chul Park, Hyo Jin Chung, Chang-Hoon Kim, Ju Wan Kang, Seong-Chul Hong, Keun-Hwa Lee, Jaechun Lee, Hye-Sook Lee, Jeong Hong Kim A334 The Sensitization to Russian Thistle on Mongolian Patients Narantsetseg Logii A335 The Association Between Air Pollution, Allergic Sensitization to Inhalant Allergens and Airway Hyperresponsiveness in Ulaanbaatar, Mongolia Munkhbayarlakh Sonomjamts, Enkhbayar Bazarsad A336 Pre-Coseasonal Treatment with a 5-Grass Pollen Sublingual Tablet in Adults Demonstrated a Reduction on Asthma Symptoms in Réunion Island Bashir Omarjee A337 Peak Expiratory Flow Rate Reference Values for Children Aged 5-14 Years Old in Beijing Urban Area Shuo LI A338 Soybean Storage Proteins As the Main Allergen in a Patient with Food-Dependent Exercise-Induced Anaphylaxis Due to Tofu Miyuki Hayashi, Ruby Pawankar, Shingo Yamanishi, Toru Igarashi, Yasuhiko Itoh A339 A Study of Allergy Skin Prick Test with Weed Pollen Oyuntsatsral Batsaikhan, B. Gantulga, B. Enkhbayar, S. Munkhbayarlakh, L.Narantsetseg A340 The Role of Neurotrophin in a Murine Model of House Dust Mite Induced Allergic Rhinitis Pei-Chi Chen, Jiu-Yao Wang A341 Mimotopes of the Major Shellfish Allergen Tropomyosin Suppress Splenocyte Proliferation and Local Cytokine Expression in a Mouse Model of Shellfish Allergy Nicki Y. H. Leung, Christine Yee Yan Wai, Patrick S.C. Leung, Ka Hou Chu A342 A Questionnaire Survey on Understanding of Atopic Dermatitis Among Korean Patients and Caregivers Eun Jin Doh, Dong Hun Lee, Mira Choi, Hyun-Sun Yoon, Kyu Han Kim, Ji Soo Lim A343 Comparison of the Dosage of Bronchodilators in the Bronchodilator Response Test in Children Ji Hyeon Baek, Man Yong Han, Seung Jin Lee, Youhoon Jeon, Kyung Suk Lee, Young-Ho Jung, Hye Mi Jee, Youn Ho Shin A344 The Expression and Effect of Natural Killer T Lymphocytes in Chidren with Asthma Yi Jiang, Miao Liu A345 Oral Provocation Test in Non-Steroidal Anti-Inflammatory Drug Hypersensitive Patients Referred to Singapore General Hospital Chaw Su Naing, Tze Chin Tan, Yong Yeow Chong A346 Different Phenotypes of Bhr (bronchial hyperresponsiveness) By Natural Course in Children and It’s Characteristics Young-Ho Kim, Eun Lee, Song-I Yang, Hyun-Ju Cho, Hyung Young Kim, Ji-Won Kwon, Young-Ho Jung, Byoung-Ju Kim, Ju-Hee Seo, Ho-Jang Kwon, Hyo-Bin Kim, So-Yeon Lee, Soo-Jong Hong, Soo Hyun Kim A347 Spectrum of Allergens Causing Allergic Rhinitis and Asthma in Urban Bangalore, India − a Study of 120 Patients Jacqueline Elizabeth Joseph, Soumya M. S, Ruby Pawankar, Harshitha Kumar A348 High Prevalence of Wheezing Illness and Risk Factor of Atopic Asthma Progression in Korean Preschool Children Sohyoung Yang, Sung-Il Woo A349 Clinical and Laboratory Screening of Primary Immunodeficiency Diseases: International Effects Nima Rezaei A350 The Effect of Helicobacter Pylori Infection in Atopic Individuals Sukran Kose, Basak Gol Serin, Arzu Didem Yalcin, Süheyla Serin Senger, Mehmet Erden, Ertan Serin A351 Clinical Spectrum and Natural History of Chronic Urticaria in Hong Kong Children Agnes Sze-Yin Leung, Ting Fan Leung A352 Skin Prick Test Reactivity to Common Pollen Aeroallergens in Patients with Allergic Rhinitis − in Urban Bangalore, India Harshitha Kumar, Soumya M.S., Jacqueline Elizabeth Joseph, Ruby Pawankar A353 Seasonal Patterns of Asthma-Related ED Visits and Admissions in Children and Adolescents Who Visited Emergency Rooms of Korea in 2007-2012 Eun Hee Chung A354 Prevalence of Atopic Dermatitis and Its Associated Risk Factors in Elementary School Children: A Cross-Sectional Study in Gyeonggi-Do, South Korea Eunji Kim, Young Yoo, Ji Tae Choung, Sungchul Seo, In Soon Kang, Jue Seong Lee, Ji Hyen Hwang A355 Intralymphatic Immunotherapy for Dermatophagoides Farinae, Dermatophagoides Pteronyssinus, Cat, and/or Dog Allergy in Patients with Allergic Rhinitis: 1 Year Follow-up Sang Min Lee, Joo Hyun Jung, Seung Joon Choi, Eugene Joe, Hyunjung Hwang, Shin Myung Kang, Yu Jin Kim, Sun Young Kyung, Jeong-Woong Park, Sung Hwan Jeong, Sang Pyo Lee A356 Respiratory Syncytial Virus Regulates IL-33 Expression in Bronchoalveolar Cells and Lung Tissue in Vivo Alina Gaisina, Igor Shilovskiy, Aleksandra Nikonova, Oleg Kamyshnikov, Musa Khaitov, Alexander Mitin, Komogorova Viktoriya, Marina Litvina, Nina Sharova A357 The Prevalence of Parent-Perceived Food Hypersensitivity in Pre-School Children Attending a Tertiary Care Hospital in Malaysia Faizah Mohamed Jamli A358 Th2 Dominant Airway Inflammation Induced By House Dust Mite Chitin Is Dependent on TNF-a and NKT Cell Da-Il Yoon, Jun-Pyo Choi, Han-Byul Choi, Yoon-Keun Kim, Hyeon-Il Choi A359 Geographic Variations in the Patterns of Sensitization to Aeroallergens in Korean Adults: A Multi-Center Study Mingyu Kang, Mi Yeoung Kim, Sujeong Kim, Eun-Jung Jo, Seoung-Eun Lee, Woo-Jung Song, Sang Min Lee, Chansun Park, Yoon-Seok Chang, Jaechun Lee, Young-Koo Jee, Inseon S Choi, Kyung-up Min, Sang-Heon Cho A360 Experimental Mouse Model of Asthma Induced By Dust Mite Dermatophagoides Pteronyssinus allergenic Extract Anton Laskin, Oleg Kamyshnikov, Alexander Babakhin, Valentina Berzhets, Musa Khaitov A361 Severe Refractory Pulmonary Complications in Children with Mycoplasma Pneumoniae Pneumonia Sejin An, Jae Ho Lee A362 Usefulness of Interactive e-Learning Education Program for Asthma Guideline Sung-Yoon Kang, Yoon-Seok Chang, Kyung-up Min, Sang-Heon Cho, Sae-Hoon Kim, Yong Eun Kwon, Young-Koo Jee, Tae-Bum Kim, Hee-Bom Moon, Hye-Kyung Park A363 Airway Inflammation Induced By House Dust Mite Derived Vesicles Is Mainly Induced By LPS Derived from Gram Negative Bacteria in Dust Mite. Sang-Yoon Kim, Jun-Pyo Choi, Han-Ki Park, Ji-Hyun Lee, Yoon-Keun Kim A364 Changes in the Recognition of Causal Allergen, Its Avoidance, and Allergen Specific Immunotherapy after Skin Prick Test / Intradermal Test, Nasal Provocation Test, and Intralymphatic Immunotherapy in Patients with Allergic Rhinitis: 1 Year Follow-up Hyunjung Hwang, Eugene Joe, Sang Min Lee, Seung Joon Choi, Joo Hyun Jung, Yong Han Seon, Shin Myung Kang, Yu Jin Kim, Sun Young Kyung, Jeong-Woong Park, Sung Hwan Jeong, Sang Pyo Lee A365 Laboratory Diagnostic of Staphylococcal Sensitization Natalya Khramykhoverchenko A366 Th-17 Regulatory Cytokines Enhance Neutrophil Production of IL-17 during Asthma Saleh Al Muhsen, Asma Sultana, Rabih Halwani, Ahmed Bahammam A367 Diagnostic Value of Serum Total IgE and Prediction of Cut-Off Value to Recommend Mast in Allergic Rhinitis Hyung Chae Yang, Sun Kyung Kim, Kwang Il Nam A368 Diagnostic Value of an Increase in FEV1 and/or FVC >12% and >200 mL from Baseline after Bronchodilators for Diagnosis of Asthma Jeong-Eun Kim, Ju Suk Lee, Ji Hyun Lee, Kyung Woo Kang A369 Combined Use of Fractional Exhaled Nitric Oxide and Bronchodilator Response in Predicting Future Loss of Asthma Control Among Children with Atopic Asthma Je-Kyung Kim, Youn-Soo Hahn, Jae-Yub Jung A370 Antigen-Specific IgA Plays an Important Role in Mucosal Immune Response in Allergic Children : Measurement of Secretory IgA and Antigen-Specific IgA Yosuke Baba, Sususmu Yamazaki, Eisuke Inage, Mari Mori, Yoshikazu Ohtsuka, Masato Kantake, Toshiaki Shimizu, Asuka Honjoh, Tomoaki Yokokura A371 Why Teaching Pediatrics Trainees about Anaphylaxis and Its Acute Management Is Essential: Cross Sectional Survey. Mehdi Adeli, Shaza Ali Mohammed Elhassan, Caroline Beck A372 Prevalence and Clinical Characteristics of Local Allergic Rhinitis in Children Min Sun Na, Heysung Baek, Seung Jin Lee, Ji Hyeon Baek, Jungwon Yoon, Sun Hee Choi, Young-Ho Jung, Youn Ho Shin, Man Yong Han A373 House Dust Mites Sublingual Immunotherapy Can Influence the Long-Term Evolution of Severe Atopic Dermatitis and the Progression to Respiratory Allergy. Enrico Compalati, Maurizio Marogna A374 The Positive Distribution Characteristics of 90 Food Specific IgG in Patients with Allergic Diseases Huimin Huang, Baoqing Sun, Mingyu BAI, Yiting Huo, Peiyan Zheng, Nili Wei, Wenting Luo A375 Evaluation of Serum Levels of Osteopontin As a Potential Biomarker of Immune Activation in Patients with Allergic Diseases Elisa Villa, Anand Andiappan, Rosalba Minisini, Olaf Rötzschke, Elena Boggio, Luca Gigliotti, Nausicaa Clemente, Annalisa Chiocchetti, Umberto Dianzani, Mario Pirisi A376 Prevalence of Allergic Rhinitis in 3-6-Year-Old (preschool) Children in Chiba City (urban area), Japan Fumiya Yamaide, Syuji Yonekura, Naoki Shimojo, Yuzaburo Inoue, Yoshitaka Okamoto A377 Comparative Efficacy of Combination Nebulized Salbutamol and Fluticasone Propionate and Nebulized Salbutamol in Children with Mild Moderate Asthma Attack Retno Asih Setyoningrum, Landia Setiawati, Sri Sumei, Deddy Iskandar A378 Characteristics of Children Hospitalized with Asthma in West Nusa Tenggara General Hospital Mataram Indonesia Indriyani Sang Ayu Kompiyang A379 Identification of Phenotypes in Allergic Bronchopulmonary Aspergillosis Using Cluster Analysis Tsuyoshi Oguma, Jun Tanaka, Katsuyoshi Tomomatsu, Koichiro Asano A380 The Roles of Type 2 Innate Lymphoid Cells (ILC2) in Chronic Rhinosinusitis (CRS) Keisuke Uno, Yoshinori Matsuwaki, Kazuhiro Omura, Eika Hayashi, Norifumi Tatsumi, Hirohito Kita, Nobuyoshi Otori, Hiromi Kojima A381 Respiratory Symptoms, Signs and Spirometry Indexes Comparision in 7-12 Years Old Girls in Esfahan Metropolis and Its Far Suburb Mohammadreza Fatemi Khorasgani A382 Induction of Kruppel-like Transcription Factor (KLF4&5) By Baker’s Yeast Mannan in Human Bronchial Epithelial and Smooth Muscle Cells Dukhee/Betty Lew, Kim/S. Lemessurier, Joseph/a Moore, Jeoung-Eun Park, Ae-Kyung Yi, Chi/Young Song, Kafait/U Malik A383 Korean Profile in Childhood Asthma Severity Classification Dongin Suh, Ja Kyoung Kim, Hyeon-Jong Yang, Bong-Seong Kim, Youn Ho Shin, So-Yeon Lee, Geunhwa Park, Woo Kyung Kim, Hyo-Bin Kim, Heysung Baek, Dae Hyun Lim, Dae Hyun Lim, Jin Tack Kim A384 Prevalence of Food Sensitization, IgE-Mediated and Non-IgE-Mediated Food Allergy Among Pediatric Patients Diagnosed with Autism Spectrum Disorders Aimee Lou Manalo Nano A385 Component-Resolved Diagnostic Study of Dermatophagoides Pteronyssinus Major Allergen Molecules in a Southern China Wenting Luo, Baoqing Sun A386 Risk Factors for Systemic and Local Reactions to Subcutaneous Allergen Immunotherapy Hikmet Tekin Nacaroglu, Semiha Bahceci Erdem, Ozlem Sumer, Sait Karaman, Canan Sule Unsal Karkiner, Suna Asilsoy, Ilker Gunay, Demet Can A387 Literature Review and Current Treatment Options for Cyclical Anaphylaxis Danielle Kiers A388 The Effect of Surfactant Protein D in Acute Lung Injury and Pulmonary Fibrosis Induced By Bleomycin Hsu Han Yin, Jiu-Yao Wang A389 Activation of Endothelial Cells to Release Hsp90, an Activator of the Prekallikrein-High Molecular Weight Kininogen (HK) Complex Allen Kaplan, Kusumam Joseph, Baby G. Tholanikunnel A390 The Effect of Climatic Treatment in 51 Asthmatic Children from Areas Severely Polluted Environment of Northern Moravia, Czech Republic Radim Dudek A391 Comparison of Some Vitamin Groups in Asthmatic Patients Gulden Bilgin, Hatice Surer, Aytun Sadan Kilinc, Dogan Yucel A392 Sensitization in Children with Atopic Dermatitis: A Single Center Study Ji Young Lee, Jihyun Kim, Hea-Kyoung Yang, Minji Kim, Sang-Il Lee, Kangmo Ahn A393 Staphylococcal Enterotoxin IgE Sensitization: A Risk Factor for COPD Overlap in the Elderly Asthma? Sung Do Moon, Byung-Keun Kim, Sang-Heon Cho, Kyung-up Min, Yoon-Seok Chang, Heung Woo Park, Hye-Ryun Kang, Woo-Jung Song, Min-Koo Kang, Ju-Young Kim, Kyonghee Sohn, Ha Kyung Won, Seoung-Eun Lee, Kyung-Mook Kim, Claus Bachert A394 The Effects of Probiotics and PparÎ(3) on the Murine Model of Allergic Asthma Miao-Hsi Hsieh, Jiu-Yao Wang A395 Adult Patients’ Views on the Design of Adrenaline Autoinjectors Helen Smith, Clare Brown, Christina Jones, Mark Davies A396 CCL22 miRNA modulated Th1 responses and induced therapeutic effects on OVA-induced mouse model of asthma Won Suck Yoon A397 Clinical, Histological, and Skin Microbiome Characteristics of Head and Neck Dermatitis in Atopic Dermatitis Hemin Lee, Howard Chu, Jungsoo Lee, Jung U Shin, Chang Ook Park, Kwang Hoon Lee, Seo Hyeong Kim, Ji Yeon Noh, Ji Hye Kim A398 MicroRNA-432 modulates Th1 responses and induced therapeutic effects in atopic like murine model. Won Suck Yoon A399 Case Report of Near-Fatal Asthma Due to Snail Allergy in a House Dust Mite-Allergic Adult Jean-Pierre L’huillier, Jean-Eric Autegarden, Catherine Bertrand, Dominique Tardy A400 Relationship Between Gut Microbiota in the First 3 Months of Life and Infant Immune Function at Age 12 Months Intan Hakimah Ismail, Mimi Tang, Paul Licciardi, Frances Oppedisano, Robert Boyle, Roy Robins-Browne A401 A Pediatric Case of Food-Dependent Exercise-Induced Anaphylaxis Due to Spice Allergy Hisako Yagi, Harumi Koyama, Yutaka Nishida, Takumi Takizawa, Hirokazu Arakawa A402 Correlations Between Objective Severity Score and Each of the Subjective Severity Intensity in Atopic Dermatitis Hong Kyu Kang, Hemin Lee, Jungsoo Lee, Jung U Shin, Kwang Hoon Lee, Kwang Hoon Lee, Howard Chu, Chang Ook Park A403 Barrier Related Gene Mutations in Atopic Dermatitis Na Young Yoon, Hyeyoung Lee, Seong Jun Seo, Eunhee Choi, Hye-Young Wang, Minyoung Jung, Eung Ho Choi, Dong Hye Kim A404 Clinical Utility of Basophil Activation Test (BAT) in the Diagnosis of Drug Induced Anaphylaxis Joo-Hee KimYoung-Sook Jang, Jeong-Hee Choi, Sunghoon Park, Young Il Hwang, Seung Hun Jang, Ki-Suck Jung A405 Feeding Shapes the Colonization of Gut Microbiota and Associated with Total IgE in Infant Mi-Jin KangDongin Suh, Eun Lee, Kil Yong Choi, Young-Ho Jung, Song-I Yang, Bong-Soo Kim, Ha-Jung Kim, Juneyoung Koh, Hyun-Jin Kim, Kangmo Ahn, Youn Ho Shin, Hyun-Ju Cho, Byoung-Ju Kim, Young-Ho Kim, Yean Jung A406 CD8(+)T Cell-Intrinsic Smad4 Suppresses Th2 Responses in the Pathogenesis of Contact Hypersensitivity Mizuko Mamura, Jeong-Hwan Yoon, Susumu Nakae, Inkyu Lee, Isao Matsumoto, Takayuki Sumida, Jin Soo Han, Katsuko Sudo, Ji Hyeon Ju A407 Immune-Modulatory Genomic Properties Differentiate Gut Microbiotas of Infants with and without Eczema Gaik Chin Yap, Wen Tso Liu, Seungdae Oh, Pei Ying Hong, Chiung Hui Huang, Marion Aw, Lynette Shek, Bee Wah Lee A408 The Effect of Medication in OSA Patients with Allergic Rhinitis Young Seok Byun, Sung Wan Kim, Tae Kyung Koh, Joong-Saeng Jo, Kun Hee Lee, Chul Kwon, Sung-Hwa Dong A409 A Case of Generalized Pustular Psoriasis Mimicking Acute Generalized Exanthematous Pustulosis Myung Shin Kim, Chansun Park A410 Anaphylaxis Caused By Gummy Jelly Ingestion: A Case Report Han Seok Cho, Min-Ju Kim, Min Ji Kim, Young Ok Park, Hye Yeong Lee, Hee Seong Kim, Eun Lee, Hyun-Ju Cho, Jinho Yu, Soo-Jong Hong, Keum Hee Hwang A411 Serum Folliculin As a Novel Biomarker for Asthma Jung-Hyun Kim, You Sook Cho, Sae-Hoon Kim, Hyouk-Soo Kwon, Mira Yoo, Hyo-Jung Kim, So-Young Park, Bomi Shin, So Young Park, Bomi Seo, Min-Gu Kim, Hee-Bom Moon, Jin-Ah Park, Tae-Bum Kim, Jaemoon Lee A412 Corticosteroid Nasal Irrigations after Endoscopic Sinus Surgery in the Management of Chronic Rhinosinusitis with Asthma Jin Hyeok Jeong, Tae Wook Kang, Han Seok Yoo, Yong Hee Cho, Seok Hyun Cho, Kyung Rae Kim A413 Capsaicin Injection in Neonatal Period Potentiates Intensity and Duration of Atopic Dermatitis of Rats. Jue Seong Lee, Sun-Ho Kee, Sewon Kim, Young Yoo, Heung Sik Na, Seung Keun Back A414 Comparison Between the Impulse Oscillometry System, Spirometry, Feno, Lung Clearance Index and Asthma Control and Exacerbation Status. Seung Jin Lee, Bo Seon Seo, Ji Hyeon Baek, Kyung Suk Lee, Young-Ho Jung, Hye Mi Jee, Youn Ho Shin, Man Yong Han, Mi-Ae Kim A415 The Association of Exhaled Nitric Oxide and Airway Hyperresponsiveness in Patients with and without Asthma Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A416 Effects of Air Pollution on Allergic Rhinitis in Korea Jisun Park A417 Exhaled Nitric Oxide in Korean Children with Allergic Rhinitis Seung Hyun Moon A418 A Questionnaire of Children with Asthma or Asthma and Allergic Rhinitis Rong Jun Lin, Ren Zheng Guan A419 A Case of Trimebutine-Induced Morbilliform Skin Eruption Gyeong Yul Park, Hyun-Sun Yoon A420 Comparison of Methacholine and Mannitol to Predict Exercise-Induced Bronchoconstriction in Children with Asthma Woo-Hyeok Choi, Heysung Baek A421 Different Inflammatory Mechanisms of Human Metapneumovirus and Respiratory Syncytial Virus Jin-Sung Park, Eunmi Kwon, Zac Callaway, Chang-Keun Kim, Takao Fujisawa A422 Sputum Microbiota in Chinese Adults with Eosinophilic Versus Non-Eosinophilic Asthma Qingling Zhang, Rihuang Qiu, Naijian Li, Zhaowei Yang, Jing Li, Kian Fan Chung, Nanshan Zhong A423 Which Clinical Features Are Useful in Predicting Presence of Staphylococcus Aureus colonization/Infection in Childhood Atopic Dermatitis? Kam Lun E. Hon, Yin Ching K. Tsang, Ting Fan Leung A424 Clinical Significance of Increased VEGF, TGF-Î(2)(1,) and YKL-40, a Chitinase like Protein, in Serum of the Children with Asthma Yoon Young Jang, Hai Lee Chung, Seung Gook Lee, Ji Hyun Na, Jong Hoon Lee A425 Analysis of Follow-up Results of Mannitol Challenge Test in Asthma Patients Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A426 Analysis of 68 Oral Walnut Challenge Tests Mikita Yamamoto, Sakura Sato, Noriyuki Yanagida, Ayako Ogawa, Kanako Ogura, Kyohei Takahashi, Kenichi Nagakura, Shigehito Emura, Tomoyuki Asaumi, Katsuhito Iikura, Motohiro Ebisawa, Yu Okada A427 Effectiveness of Air Filters Intervention in Allergic Rhinitis Jiaying Luo, Xiao Lan, Baoqing Sun, Zhao Chen, Guiyuan Sun, Shimin Li, Jiaqing Hu A428 The Relationship Between Airway Hyperresponsiveness to Mannitol and Atopy in Asthmatic Children Woo-Hyeok Choi, Heysung Baek A429 Anaphylactoid Reactions to N-Acetylcysteine in the Treatment of Aacetaminophen Overdose Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A430 Effect of Prenatal Maternal Distress and GSDMB Polymorphism on the Development of Recurrent Wheezing in Early Childhood: COCOA Study Yean Jung Choi, Si Hyeon Lee, Young-Ho Kim, Mi-Jin Kang, Hyun-Ju Cho, Eun Lee, Song-I Yang, Youn Ho Shin, Kangmo Ahn, Kyung Won Kim, Yoon Hee Kim, So-Yeon Lee, Hyoung Yoon Chang, In Ae Choi, Kyung-Sook Lee, Yee-Jin Shin A431 Vitamin D Level in Allergic Rhinitis: A Systemic Review and Meta-Analysis Yoon Hee Kim, Min Jung Kim, In Suk Sol, Seo Hee Yoon, Young a Park, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Yong Ju Lee A432 Implication of Inspiratory and Expiratory Resistance and Reactance in Children with Asthma In Suk Sol, Kyu-Earn Kim, Yoon Hee Kim, Min Jung Kim, Seo Hee Yoon, Yong Ju Lee, Kyung Won Kim, Young a Park, Myung Hyun Sohn A433 The Association of Asthma Predictive Index with Asthma in Preschool Children with Recurrent Wheeze Sung Joo Park, Ji-Won Kwon, Woo Kyung Kim, Hyung Young Kim, Hyo-Bin Kim, Ju-Hee Seo, So-Yeon Lee, Gwang-Cheon Jang, Young-Ho Jung, Soo-Jong Hong, Byoung-Ju Kim, Dae-Jin Song, Yun Seok Yang, Jung Yeon Shim A434 Clinical Significance of Serum Total IgE Levels in Children with RSV-Associated Lower Respiratory Illness Yoon Young Jang, Hai Lee Chung, Ji Hye Kim, Hyun Seok Lee, Chang Ho Lee A435 Development of a Oak Pollen Emission and Transport Modeling Framework in South Korea Changbum Cho, Yun-Kyu Lim, Kyu Rang Kim, Mijin Kim, Baek-Jo Kim A436 Temperature, Humidity, and Air Pollution Affect Atopic Dermatitis Symptoms in Infants and Young Children Young-Min Kim, Youngshin Han, Jihyun Kim, Hae-Kwan Cheong, Byoung-Hak Jeon, Kangmo Ahn A437 Effects of Compound V on Pulmonary Fibrosis Model Chuang/Yao Ming, Jiu-Yao Wang, Ye/Yi Ling A438 Vitamin D Level and the Correlation with IgE in Children with Allergic Respiratory Diseases in Guangzhou China Huimin Huang, Baoqing Sun, Yun Chen, Peiyan Zheng, Nili Wei, Wenting Luo A439 Two Case Reports of Eosinophilic Gastroenteritis Associated with Allergic Disease Do Hyeong Lee, Gil-Soon Choi, Hee-Kyoo Kim, Han Su Park A440 Genome-Wide Association Study (GWAS) May Identify Common Genetic Variations Both in Immediate and Delayed Drug So-Young Park, Hyo-Jung Kim, Bomi Seo, Jung-Hyun Kim, Min-Gu Kim, Hyouk-Soo Kwon, You Sook Cho, Hee-Bom Moon, Tae-Bum Kim, Yoon Su Lee A441 Development of a Questionnaire for Secular Change of Atopic Dermatitis from Birth to 19-Year-Old. Akio Tanaka, Satoshi Morioke, Yukihiro Ohya, Naoki Shimojo, Akira Akasawa, Michihiro Hide, Hiroko Shizukawa A442 Evaluation of the Adherence Starts with Knowledge-20 (ASK-20) to Inhaled Drug in Patients with Bronchial Asthma Naoto Watanabe A443 The Epidemiology and Clinical Manifestation of Hmpv Infection in Children during Recent 4 Years: 2011-2014 Meeyong Shin, Myeong Sun Jang A444 Neutropenia Induced By Intravenous Immunoglobulin Young-Hee Nam, Yeo Myeong Noh, Dong Sub Jeon, Hee-Joo Nam, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A445 A First Case of Lymphocytic Interstitial Pneumonitis in Healthy Child Ji-in Jung, Ha-Su Kim, Hyun-a Kim, Jin-a Jung A446 Cytokine Production upon House Dust Mite Stimulation of Cord Blood Mononuclear Cells from Caesarean Section-Delivered Singaporean Infants Anne Goh, Rajeshwar Rao, Bindu Nandanan, Ruurd Van Elburg, Chua Mei Chien, Juandy Jo, Johan Garssen, Johan Garssen, Leon Knippels, Elena Sandalova, Wen Chin Chiang A447 Dress Syndrome with Acute Interstitial Nephritis Caused By Quinolone and Nonsteroidal Anti-Inflammatory Drugs Young-Hee Nam, Ji Young Juong, Soo Jin Kim, Eun Young Kim, Su Mi Lee, Young Ki Son, Hee-Joo Nam, Ki-Ho Kim, Soo-Keol Lee A448 IL-23 Roles in the Development of House Dust Mite Allergic Sensitization and Asthma Da-Eun Park, Hye-Ryun Kang, Heung Woo Park, Hyun Seung Lee, Yoon-Seok Chang, Jung-Won Park, Sang-Heon Cho, Kyung-up Min, Woo-Jung Song A449 Exposure Profile of Indoor Risk Factors in Dwellings of Children with Atopic Dermatitis Hyunwook Lim, Sungchul Seo, Ji Tae Choung, Young Yoo, Jun-Sik Park, Byung Kwan Kim A450 Epidemiological Characterization of Blood Eosinophils in the Elderly Population Ha Kyeong Won, Hye-Ryun Kang, Byung-Keun Kim, Sung Do Moon, Ju-Young Kim, So-Hee Lee, Woo-Jung Song, Heung Woo Park, Min-Koo Kang, Sun-Sin Kim, Sang-Heon Cho, Kyung-up Min, Yoon-Seok Chang, Kyoung Hee Sohn, Kyung-Mook Kim, Ki-Woong Kim, Hak Chul Jang A451 Stevens-Johnson Syndrome Caused By Methotrexate in the Treatment of Psoriasis Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A452 Genetic Determinants for Lung Function Growth in Asthmatic Children Ting Fan Leung, Man Fung Tang, Hing Yee Sy, Wa Cheong Chan, Wilson Wai San Tam A453 The Power of Allergen Specific Ig E in the Classification of Rhinitis, Korean National Hanes 2010 Seung Kyu Chung, Sujin Kim, Sang Duk Hong, Hyo Yeol Kim Hyo Yeol Kim, Hun-Jong Dhong, Jong in Jeong A454 Analysis of Allergen Immunotherapy Practice and Patients’ Knowledge and Attitude about Allergen Immunotherapy in a Single Tertiary Hospital in Korea Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A455 Roles of Staphylococcal Enterotoxin B in House Dust Mite-Induced Acute Asthma Models Ji Won Lee, Mingyu Kang, Soon-Hee Kim A456 A Clinical Comparison of Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome in a Single Tertiary Hospital in Korea Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A457 The Beneficial Effect of Lactobacillus Gasseri PM-A0005 and Its Immunoregulatory Protein PMA5P40 on Milk-Induced Allergic Enteritis Yung-I Hou, Jiu-Yao Wang A458 Relationship Between Serum Folate Levels and Risks of Allergic and Respiratory Diseases in Early Childhood: The Mothers and Children’s Environmental Health Study Ja Hyeong Kim, Seol Jae Hee, Eun-Hee Ha, Hyesook Park, Mina Ha, Yun-Chul Hong, Yangho Kim, Namsoo Chang A459 Effects of Vitamin D in Patients with Chronic Rhinosinusitis Yuta Soma, So Watanabe, Ruby Pawankar, Ruby Pawankar, Harumi Suzaki, Harumi Suzaki, Hitome Kobayashi A460 Clinical Features of Systemic Contact Dermatitis from Ingestion of Rhus Young-Hee Nam, Chansun Park, Soo-Keol Lee A461 Sublingual Immunotherapy Efficacy in Patients with Atopic Dermatitis in Korea Jongrok Lee, Jooyoung Roh, Haryeong Ryu A462 Characteristics of Serious Adverse Drug Reactions in a Tertiary University Hospital Cheol-Woo Kim, Jae Hwa Cho, Mi Ra Eom, Ji Young Kang, Hye Gyeung Lee A463 Eyelid Dermatitis: Patch Test Results during a 15-Year Period in Korea and Evaluation of Metal Contents in Eye Shadows Hae Young Choi, Hye Jin Lee, Ju Yun Woo, Ji Yeon Byun, You Won Choi A464 Relationship Between Lipid Levels and Risks of Allergic and Respiratory Diseases in Early Childhood: The Mothers and Children’s Environmental Health Study Ja Hyeong Kim, Eun-Hee Ha, Hyesook Park, Mina Ha, Yun-Chul Hong, Yangho Kim, Namsoo Chang A465 IL-32 in the Induced Sputum of Patients with Asthma Jae-Woo Kwon, Hun Soo Chang, Jeong-Seok Heo, Jong-Uk Lee, Jong-Sook Park, Eusom Kim, Soo Hyun Kim, Choon-Sik Park A466 Clinical Characteristics of Patients with Chromium Allergy in a Single University Hospital in Korea Hae Young Choi, Ji Yeon Byun, Ju Yun Woo, You Won Choi A467 Efficacy and Safety of Oral Acitretin in Chronic Hand Eczema Hyun-Ju Jin, Jin-Hwa Son, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Margaret Song, Hyun-Chang Ko, Moon-Bum Kim, Hoon-Soo Kim, Byung Soo Kim A468 Atypical Antipsychotics and Anticholinergic Agents Mimicking Anaphylaxis Sheryl Van Nunen, Dinh Van Nguyen, Anthony Elias, Susannah Olivia Lauer A469 Introducing Reach (Reliable Estimation of Atopic dermatitis in ChildHood): Novel, Questionnaire-Based Diagnostic Criteria for Childhood Atopic Dermatitis Seung-Chul Lee, Ho-June Lee, Jung Min Bae A470 Comprehensive Assessment to Identify the Causative Factors in Oral Allergy Syndrome Emi Ono A471 Comparison of Interpretation Methods in Allergic Skin Test Sung-Hwa Dong, Tae Kyung Koh, Young Seok Byun, Sung Wan Kim, Joong-Saeng Jo, Chul Kwon, Kun Hee Lee A472 Refraining Aminophylline Use Increases Hospitalization Among Children with Acute Asthma: A 10-Years Retrospective Cohort Study Li-Fan Liu A473 The Prevalence and Risk Factors of Atopic Dermatitis from Nationwide Study for Korean School Students Sunghee Lee A474 Probiotic Recombination Protein Effect on Atopic Dermatitis Wei-Leng Chen, Jiu-Yao Wang A475 Allergic Sensitization Status in Various Inflammatory Skin Diseases Youin Bae, Gyeong-Hun Park A476 Two Cases of Good’s Syndrome: A Rare Acquired Immunodeficiency Associated with Thymoma Suk Yeon Kim A477 IL-23 Has a Role to Play in the Development of Asthma in Short-Term Cigarette Smoke Exposure-Induced House-Dust Mite Allergic Model Hyun Seung Lee, Woo-Jung Song, Mingyu Kang, Han-Ki Park, Da-Eun Park, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Hye-Young Kim, Kyung-up Min, Sang-Heon Cho, Ji-Won Lee, Boram Bae, Jung-Won Park A478 The Relationship Between the Relevance of Allergic Disease and the Value of Non-Specific IgE Yasuhiro Suzuki A479 Two Caces of Prawn Allergy in Adult Patients Ismet Bulut, Zeynep Ferhan Ozseker A480 Early Gut Bifidobacterium Breve and B. Catenulatum Colonisation Differentially Modulate Eczema Risk in Children at High-Risk of Developing Allergic Disease Intan Hakimah Ismail, Robert Boyle, Paul Licciardi, Frances Oppedisano, Roy Robins-Browne, Mimi Tang A481 Effects of Chronic Repeated Exposure of Staphylococcal Enterotoxin B on Allergic Asthma Model in Mice Ji Won Lee, Hyun Seung Lee, Mingyu Kang, Da-Eun Park, Han-Ki Park, Soon-Hee Kim, Woo-Jung Song, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Chang-Han Park, Suk-Il Chang, Sook-Hee Song, Kyung-up Min, Sang-Heon Cho, Boram Bae A482 Skin Prick Test Result and Allergen Immunotherapy in Children with Allergic Rhinitis Grace Shieh A483 Role of Brp-39 in RSV-Induced Airway Inflammation in Mice Min Jung Kim, Jung Yeon Hong, Seo Hee Yoon, Doo Hee Shim, In Suk Sol, Yoon Hee Kim, Mi Na Kim, Kyung Eun Lee, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Jae Myun Lee A484 Long-Term Outcomes of Twenty-Four Adults with Primary Immunodeficiency from a Single Centre in Singapore Hiok Hee Chng A485 Breast Feeding Increases the Risk of Food Sensitization but Does Not Affect Food Allergy in Young Children with Atopic Dermatitis Dong Chan Kim, Song-I Yang, Hae Ran Lee, An Deok Seo, So Yeon Lee A486 IgE Immunoadsorption Knocks Down Anaphylaxis. Alessandro Fiocchi, Maria Cristina Artesani, Paola Francalanci, Lamia Dahdah, Thomas Schreiner A487 Burden and Correlates of Cigarette Smoking and Respiratory Airway Obstruction: An Observation in Urban Adult Population of West Bengal (India) Kaushik Chakraborty A488 Blood Eosinophils Could Predict Sputum Eosinophilia? : A Comparison Between Asthma and Non-Asthmatic Chronic Cough in the Elderly Ha Kyeong Won, Ju-Young Kim, Eun-Jung Jo, Kyoung Hee Sohn, Kyung-Mook Kim, Heung Woo Park, Yoon-Seok Chang, Sang-Heon Cho, Woo-Jung Song, Byung-Keun Kim A489 Complementary and Alternative Medicine for Allergic Rhinitis in Japan Syuji Yonekura, Yoshitaka Okamoto A490 Impact of Cognitive Impairment on Asthma Control Status in Elderly Asthmatics Gyu Young Hur, Young Min Ye, Joo-Hee Kim, Ki-Suck Jung, Junga Kim, Jae Jeong Shim, Hae-Sim Park A491 The Association Between Respiratory Tract Infection and Reactive Oxygen Stress Kazuhiro Sekimoto, Kazuko Sugai, Keiji Tsuchimoto, Hiromi Uehara, Masanori Ikeda A492 The Risk Factors and Lung Function of Current Allergic Rhinitis Due to Dust Mite Sensitization Euncho Chung, Kang Seo Park, Yean Jung Choi, Jeewon Park, Soo-Jong Hong, So Yeon Lee A493 Cloning and Expression of Recombinant Blomia Tropicalis Dust Mite Allergen Blo t 7 Alain Jacquet, Arun Buaklin, Nat Malainual A494 Seasonal Variations of Airborne Pollen in Bangalore, India Roopashree S A495 Pollen Observation and Use of Data Kyu Rang Kim, Mijin Kim, Changbum Cho, Baek-Jo Kim, Jae-Won Oh, Mae Ja Han A496 The Effect of Cord Serum 25-Hydroxyvitamin D (25(OH)D) on the Development of Atopic Dermatitis in First 3 Years of Life : Cocoa Study Hyun-Ju Cho, Youn Ho Shin, Eun Lee, Young-Ho Kim, Darae Lee, Mi-Jin Kang, Song-I Yang, Kangmo Ahn, Kyung Won Kim, Yoon Hee Kim, Hye-Sung Won, Soo Hyun Kim, Suk-Joo Choi, Young Han Kim, Jong Kwan Jun, Eun-Jin Kim, Jeom Gyu Lee, So-Yeon Lee, Soo-Jong Hong, Dongin Suh A497 Contribution of Stem Cell Factor Autocrine/Paracrine Mechanism to Aberrant Proliferation of Mast Cells Yosuke Amagai, Akane Tanaka, Hiroshi Matsuda A498 A Randomized Dbpc Dose-Finding Multicenter Trial of Sublingual Immunotherapy (SLIT) Allergoid Tablets in House Dust Mites (HDM) Allergic Patients Ralph Mösges, Pauline Dieterich, Anatoli Astvatsatourov, Christoph Hüser, Jaswinder Singh, Kija Shah-Hosseini, Silke Allekotte, Enrico Compalati A499 Depression and Allergy in the Elderly: A Community Population Analysis Kyoung Hee Sohn, Woo-Jung Song, Byung-Keun Kim, Ju-Young Kim, Min Suk Yang, So-Hee Lee, Sae-Hoon Kim, Hye-Ryun Kang, Heung Woo Park, Sun-Sin Kim, Kyung-up Min, Sang-Heon Cho, Yoon-Seok Chang A500 The Integrated Analysis of Correlation Between Total IgE and Other Immunological Factors in Allergic Diseases Woo-Sung Chang, Ji-Hye Do, Yeon-Seop Kim, Dankyu Yoon, Hye-Sun Lim, Jeom-Kyu Lee, Eun-Jin Kim A501 Pattern of Allergic Diseases Among Military Servicemen Referred to a Clinical Immunology/Allergy Service in Singapore Bernard Thong, Yew Kuang Cheng, Jinfeng Hou, Khai Pang Leong, Justina Tan, Faith Chia, Grace Chan, Sze-Chin Tan, Teck Choon Tan, Chwee Ying Tang, Hiok Hee Chng A502 A Case of Rifampicin-Induced Hypersensitivity Diagnosed By the Lymphocyte Activation Test with Successful Desensitization Chan-Sun Park, Mi Yeoung Kim, Eun-Young Kim, Jae-Gook Shin, Jae-Hyeog Choi, Saegwang Park, Yeonye Kim A503 Analysis of Individual Case Safety Reports of Drug-Induced Anaphylaxis Based on Korea Adverse Event Reporting System Database Kyung-Hwan Lim, Jae Woo Jung, Mingyu Kang, Ju-Young Kim, Ju-Young Kim, Hyun Jeong Kim, Yeon-Ju Woo, Soo-Youn Jung, Hye-Ryun Kang, Hye-Ryun Kang A504 Impact of Processes Certification on the Liability of Anti-Dust Mites Bed Covers Thierry Porée, Nabile Boukhettala, Emeline Furon A505 Localisation Kinetics of Aluminium after Subcutaneous Injection in a Rat Model Alan David Bullimore, Matthew Heath, Simon Hewings, Murray Skinner A506 Periostin Levels in Exhaled Breath Condensate of Competitive Athletes, Asthmatics and Healthy Subjects - Associations with Outdoor Ambient Conditions Marcin Kurowski, Hubert Krysztofiak, Aleksandra Wardzynska, Marzanna Jarzebska, Janusz Jurczyk, Marek L. Kowalski A507 The Role of PKR Pathway in Acute Exacerbation of Severe Bronchial Asthma So Ri Kim, Yong Chul Lee, Dong Im Kim, Yang Keun Rhee, Heung Bum Lee, Seoung Ju Park, Yeong Hun Choe Choe, Seung Yong Park A508 Diversity of Clinical Manifestations and Treatment Responses for Idiopathic Hypereosinophilic Syndrome Joo-Hee Kim, Sunghoon Park, Young Il Hwang, Seung Hun Jang, Ki-Suck Jung A509 Effect of Dexamethasone in Th17 Cell Mediating Neutrophilic Asthma Nong Guang-Min, Jiang Min A510 Allergen Profile for Asthma/Rhinitis and Eczema Among Patients in North India: An Immunocap Allergen Specific IgE Antibodies Assay Based Study Nalin Nag A511 Clinical Profile of Allergic Rhinitis in Children in Jakarta Wahyuni Indawati A512 Preclinical Study on the Use of Micro Crystalline Tyrosine (MCT) Adjuvants in Allergy Immunotherapy Alan David Bullimore, Matthew Heath, Murray Skinner A513 Genetic Diversity of Filaggrin Mutation and Its Clinical Implication in East Asian Atopic Dermatitis Patients Seong Jun Seo, Won Jong Oh A514 Protein and MPL Adsorption Capacities for MCT in Candidate Therapeutic Formulations for Use in Immunotherapy, Compared Against Existing Adjuvants Alan David Bullimore, Murray Skinner, Matthew Heath, Andrew Bell A515 Interleukin-22 Gene Variation in Inflammatory Bowel Disease Alireza Zarebidoki, Hournaz Hasanzadeh, Salman Sadeghzade, Nima Rezaei A516 Immunomodulatory Effects of Adipose-Derived Stem Cell Secretome in a Mouse Model of Asthma Kyu-Sup Cho A517 Diffuse Alveolar Hemorrhage with Positive Anti-Neutrophil Cytoplasmic Antibody in a Child : A Case Report Sung-Woo Kim, Moo-Young Oh A518 Clinical Analys the Serum TARC Levels As the Condition Index of Atopic Dermatitis in the Early Infancy Munemitsu Koizumi, Kazuyo Kuzume A519 An Analysis of the Filaggrin Gene Polymorphism in Korean Atopic Dermatitis Patients Kui Young Park, Won Jong Oh A520 A New Protocol for Wheat Oral Immunotherapy in Patients with Anaphylaxis Delara Babaie, Mohammad Nabavi, Fariborz Zandieh, Mehrdad Amir Moini, Zahra Chavoshzadeh, Hamideh Seifi, Mitra Sahragard, Mehrnaz Mesdaghi, Mohammad Hassan Bemanian A521 Clinical Characteristics of Filaggrin-Related Atopic Dermatitis Patients in Korea Sun Young Choi, Yeon a No A522 Early Allergy Diagnosis in Children - Self- Administered Questionnaire Vs Medical Verification Andrzej M. Fal, Dorota Kiedik, Agnieszka Muszynska, Iwona Pirogowicz A523 Asthma Impact on Children with Food Induced Anaphylaxis Chikako Motomura, Masatoshi Wakatsuki, Yuko Akamine, Mihoko Iwata, Hiroshi Matsuzaki, Naohiko Taba, Yoko Murakami, Hiroshi Odajima A524 Case Reports of Stevens-Johnson Syndrome and Stevens-Johnson Syndrome-Toxic Epidermal Necrolysis in Systemic Lupus Erythematosus Reni Ghrahani A525 The Effectiveness of Oral Tolerance Induction for Wheat Allergy Using Two Different Intake Levels Yuri Takaoka A526 Association of Plasma Interleukin-25 Levels with Development of Aspirin Induced Airway Spasm in Asthma Jong-Uk Lee, Jeong-Seok Heo, Da-Jeong Bae, Hyun Ji Song, Choon-Sik Park, Jong-Sook Park A527 Transition of Allergic and Nonallergic Rhinitis after 2 Years in Korean Children: Preliminary Study Jae Hoon Cho, Ji Ho Choi A528 Early Onset of Psoriasis Juvenile Idiopathic Arthritis Budi Setiabudiawan, Fiska Febriana, Reni Ghrahani, Gartika Sapartini A529 Clinical Features of Immediate Hypersensitivity to Histamine H2 Antagonists and Their Cross Reactivity Chan-Sun Park, Young-Hee Nam, Mi Yeoung Kim, Gil-Soon Choi A530 Detection of Galacto-Oligosaccharide Specific IgE in Vitro Chiung-Hui Huang, Chiung-Hui Huang, Jian Yi Soh, Lynette Shek, Lynette Shek, Dianne J. Delsing, Bee Wah Lee, Bee Wah Lee, Si Hui Goh, Wen Chin Chiang, Wenyin Loh A531 The Association Between Serum Vitamin D Levels and Allergic Diseases in Elementary Schoolchildren Hea-Kyoung Yang, Ji Young Lee, Minji Kim, Kangmo Ahn, Jihyun Kim, Young-Min Kim, Hye-Young Kim, Yong Mean Park, Woo Kyung KIM, So-Yeon Lee A532 Serum Levels Specific IgE to Toxic Shock Syndrome Toxin Type 1 in Eosinophilic Chronic Rhinosinusitis with Nasal Polyp in Korean Jongin Jeong, Sang Duk Hong, Seung Kyu Chung, Hun-Jong Dhong, Hyo Yeol Kim Hyo Yeol Kim, Sujin KIM A533 Impacts of Rhizosphere Cleaning Effects of Potted Indoor Plants on the Symptoms and Stress of Students with Allergic Rhinitis in Newly Built Schools Yong-Won Lee, Hana Bak, Hye-Rim Son, Si-Eun Lee, Kwang-Jin Kim, Young-Wook Lim, Ho-Hyun Kim A534 A Case of Multiple Food Allergies with Recurrent Anaphylaxis Successively Controlled By Omalizumab Mi-Ae Kim, Man Yong Han, Young-Ho Jung, Hye Mi Jee, Seung Jin Lee, Kyung Suk Lee A535 Bepotastine-Induced Urticaria, Cross-Reactive with Other Antihistamines Jasmina Golez, Jaechun Lee, Eunkyoung Lee A536 Role of SLC26a4 in Ozone - Induced Airway Reactivity and Inflammation Da-Jeong Bae, Chang-Gi Min, Jong-Uk Lee, Jong-Sook Park, Hun Soo Chang, Choon-Sik Park, An-Soo Jang A537 PAR2-Antagonist Suppresses Protease-Induced Allergic Inflammation Mediated By Degradation of Lung Epithelial Tight Junction and Generation of ROS Young-Joon Kim, Bok Kyoung Jung, Seung-Hwa Lee, Mi-Jin Kang, Sekyoo Jeong, Eun Lee, Hyun-Ju Cho, Young-Ho Kim, Song-I Yang, Seo Hee Kim, Soo-Jong Hong A538 Novel Anti-IL-4Ra Nanocarrier Approach for the Efficient Control of Lung Tissue Inflammation during Asthma Rabih Halwani, Saleh Al Muhsen, Asma Sultana, Achraf Al-Faraj, Rosan Kanana, Sibtain Afzal, Roaa Al Kufaidi A539 Clinical Factors for Improved Allergen Reactivities Induced By Subcutaneous Allergen Specific Immunotherapy with House Dust Mites during 1 Year Period Hee-Kyoo Kim, Chul-Ho Oak, Gil-Soon Choi, Ye-Jin Moon, Eun-Kee Park A540 Cytokine Gene Polymorphisms in Iranian Patients with Kidney Acute Rejection Alireza Zarebidoki, Mina Abrari, Ali Akbar Amirzargar A541 Phthalate Exposure and Obesity in Atopic Dermatitis of Korean Children and Adolescents Ju-Hee Seo, Mina Ha, Soo-Jong Hong A542 Which Drives Chronicity of Cough in Adults: Based on the Knhanes 2010-2012 Mingyu Kang, Byung-Ha Cho, Han-Ki Park, Han-Ki Park, Kyung-Mook Kim, Chang-Han Park, Heung Woo Park, Heung Woo Park, Yoon-Seok Chang, Yoon-Seok Chang, Yoon-Seok Chang, Sook-Hee Song, Mi-Kyeong Kim, Mi-Kyeong Kim, Sang-Heon Cho, Suk-Il Chang, Kyung-up Min, Kyung-up Min, Alyn Morice A543 Elevated Airway CD45RO Memory Cells in Wheezing Children with Lower Respiratory Infection Jungi Choi, Yusok Han, Jin-Sung Park, Eunmi Kwon, Chang-Keun Kim A544 Quality of Life in Obese Children with or without Atopic Disease Gartika Sapartini A545 Relation of Human microRNA in Sputum of Asthma with Influenza A Virus Infection-Induced Exacerbation Ji-Na Kim, Seungwoo Shin, Hun Soo Chang, Eun-Young Shim, Ji Ah Jun, Hyeonju Lee, Jong-Sook Park, Choon-Sik Park A546 Aeropolinologic Monitoring and Distribution of Allergoallergens in Western Georgia Revaz Sepiashvili, Darejan Khachapuridze, Sofio Gamkrelidze, Manana Chikhladze A547 Extracorporeal Membrane Oxygenation As Emergency Treatment for Patients with Near-Fatal Status Asthmaticus Seung-Eun Lee, Yun-Seong Kim, Doo-Soo Jeon, Woo-Hyun Cho, Hye-Ju Yeo, Seong-Hoon Yoon, Seung-Hyun Kim A548 Relationship of S100calcium Binding Protein A9 with Neutophilic Inflammation in Murine Asthma Model Taehyeong Lee, Hyun Ji Song, Choon-Sik Park, Ji Ah Jun, Jong-Sook Park A549 Whole-Exome Sequencing of Aatopic Dermatitis in Korean Childhood Dankyu Yoon, Yeon-Seop Kim, Woo-Sung Chang, Mi-Jin Kang, Soo-Jong Hong, Jeom-Kyu Lee, Eun-Jin Kim A550 A Case of Generalized Molluscum Contagiosum in an Adult Patient with Severe Atopic Dermatitis Minkee Park A551 Discovery of Putative Macadamia Nut Allergens By Patient IgE Binding and a Label-Free Shotgun Proteomics Approach Nanju Alice Lee, Johanna Rost, Sridevi Muralidharan, Dianne Campbell, Sam Mehr A552 Anti-FcÎμri Antibody Inhibits Allergic March in Mice By Suppressing Th17 Pathway Via Suppression of FcÎμri-Mediated Mast Cells Activation Seung-Hwa Lee, Seon-Joo Yoon, Ha-Jung Kim, Eun Lee, Song-I Yang, Young-Ho Jung, Ho-Sung Yu, Hee-Suk Kim, Yeon Hee Park, So-Yeon Lee, Jun-Sung Park A553 Clinical Characteristics and the Associated Factors of ATG Hypersensitivity Reaction Ha Kyeong Won, Min-Koo Kang, Sung Do Moon, Byung-Keun Kim, Ju-Young Kim, Sang-Heon Cho, Hye-Ryun Kang, Ji-Su Shim, Soo Jie Chung A554 Reference Value and Utility of Total Serum Immunoglobulin E in Korean Schoolchildren Jaehee Choi, Kangmo Ahn, Kwanghoon Kim, Jihyun Kim, Jiyoung Lee A555 Two-Step Prescreening Skin Testing May be Useful for Reducing Immediate Hypersensitivity Reaction to Nonionic Contrast Media: Results of 7-Year Period in a Secondary Hospital Bo Bae Park, In Young Nho, Chang-Han Park, Jang Min Kim, Suk-Il Chang A556 Prevalence of Allergic Sensitization in Patients with Allergy Rhinitis; Gwangju, Jeonnam State Study Sun Kyung Kim, Hyung Chae Yang, Kwang Il Nam A557 Analysis of IgE Binding Components of Walnut in Korean Children Effect of Cooking Methods on the Allergenicity of Walnut Proteins Jeongmin Lee, Jeongmin Lee, Sooyoung Lee, Kyunguk Jeong, Se-Ah Jeon A558 Assessment of Autonomic Nervous Function in Subjects with Cholinergic Urticaria Associated with Acquired Idiopathic Generalized Anhidrosis Midori Fujiwara, Shoko Shindo, Hiroyuki Murota, Mayuko Tahara, Aya Takahashi, Ichiro Katayama A559 Interleukin 1 Beta in Sputum of Patients with Asthma: Relation with Airway Obstruction and Neutrophilc Inflammation Jae Woo Jung, Hyun Ji Song, Taehyeong Lee, An-Soo Jang, Jong-Sook Park, Hun Soo Chang, Choon-Sik Park, Byoung Whui Choi A560 Interleukin 8 in Sputum of Patients with Asthma: Relation with Neutrophilc Inflammation and Exacerbation Min-Hye Kim, Da-Jeong Bae, Hyun Ji Song, Taehyeong Lee, Ji Ah Jun, Jong-Sook Park, An-Soo Jang, Hun Soo Chang, Young Joo Cho, Choon-Sik Park A561 Prostaglandin E2 and Transforming Growth Factor-Î(2) Play a Critical Role in Suppression of Allergic Airway Inflammation By Adipose-Derived Stem Cells Sue Jean Mun A562 Inhalation of Fine Particles Kill Alveolar Macrophages to Release IL-1alpha That Promote Inducible Bronchus-Associated Lymphoid Tissue (iBALT) Formation Etsushi Kuroda, Koji Ozasa, Ken Ishii A563 Association Between Smoking and Allergic Diseases in the Korean Adult General Population Sunmi Kim, Gyeong-Hun Park A564 Relationship of S100 Calcium Binding Protein A9 with Inflammasome Activation in Murine Asthma Model Hyun Ji Song, Taehyeong Lee, Ji Ah Jun, Hun Soo Chang, Jong-Sook Park, Choon-Sik Park A565 Cluster Analysis of Asthma Phenotypes to Predict Exacerbation in Korean Population Mi-Ae Kim, Seungwoo Shin, Jong-Sook Park, Hun Soo Chang, You Sook Cho, Hae-Sim Park, Choon-Sik Park A566 Effect of AG490 on the Expression of TH17 CELLS and Tregs in the MOUSE MODEL of Neutrophilic Asthma Zhang Min A567 Association Between the Clinical Characteristics and Disease Severity in Hospitalized Bronchiolitis Patients Younger Than Two Years Old Seo Hee Yoon, In Suk Sol, Young a Park, Yoon Hee Kim, Min Jung Kim, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim A568 Comparison Between House Dust Mite and Aspergillosis Sensitization in Patients with High Level of Tige Wu Shiquan A569 The Prevalence of Metal Allergy in the Patients with Orthodontic Appliance Yongwon Lee, Hana Bak A570 Component Resolved Diagnosis and Single Nucleotide Polymorphism Analyses: Towards the Development of Specific Immunotherapy for Allergy Maricar Wisco Ching, John Donnie Ramos A571 Clinical Features of Anaphylaxis Caused By Peanut, Tree Nuts and Seeds in Children and Adolescents: Multi-Center Study with 126 Patients Kyunguk Jeong, Sooyoung Lee, Kangmo Ahn, Myung Hyun Sohn, Kyung Won Kim, So-Yeon Lee, Tae Won Song, Youhoon Jeon, Jihyun Kim, Taek Ki Min, Kyu-Earn Kim, Bok-Yang Pyun, Hyeon-Jong Yang, Hae Ran Lee, Youngmin Ahn, Ji-Won Kwon, Dae Hyun Lim, Jeong Hee Kim, Dongin Suh, Hyung Young Ki A572 A Report of Two Cases of Anaphylaxis Caused By Perilla Seed in Children Kyunguk Jeong, Byeong Sub Park, Sooyoung Lee, Se-Ah Jeon, Kyu Jung Park A573 Prenatal Fine Particulate Matter Affects Wheezing in Children with TLR4 Polymorphism: Cocoa Study Song-I Yang, Eun Lee, Hyun-Ju Cho, Young-Ho Kim, Mi-Jin Kang, Yean Jung Choi, Kil Yong Choi, Youn Ho Shin, Kangmo Ahn, Kyung Won Kim, Byoung-Ju Kim, So-Yeon Lee, Eun-Jin K A574 Intensified B Lymphocyte Depletion (IBLD) without Immunosuppressive Maintenance Treatment As a Rescue Therapy in Refractory Lupus Nephritis (LN): a 4-Year Observation. Roccatello Dario A575 Relationship Between Th17 Cells and Neutrophilic Airway Inflammation in Childhood Neutrophilic Asthma Jing Liao A576 Clinical Applications of Impulse Oscillometry in Asthma Management after Exacerbation in Preschool Children Yong Feng, Yunxiao Shang A577 Contact Allergy to Sodium Sulfite and Its Relationship to Facial Cosmetic Contact Dermatitis Yongwon Lee, Hana Bak A578 Effect of Exposure to Air Pollution on Asthma and Lung Function Development Hyung Young Kim, Byoung-Ju Kim, Ji-Won Kwon, Ju-Hee Seo, Eun Lee, So-Yeon Lee, Song-I Yang, Young-Ho Jung, Hyo-Bin Kim, Ho-Jang Kwon, Hee Ju Park A579 Role and Relational Mechanism of AG490 in Airwayinflammation in the Mouse Model of Neutrophilic Asthma Zhang Min, Nong Guang-Min, Jiang Min A580 Incidence of Adverse Reaction to Radioconstrast Media in a Single Tertiary Hospital Gyu Young Hur, Eun Jung Sim, Sora Yoon, Juwhan Choi, Junga Kim, Jae Keom Sim, Jee Youn Oh A581 Cow’s Milk Oral Food Challenge: Clinical and Laboratory Features in Korean Children Kyunguk Jeong, Byeong Sub Park, Jeong-Min Lee, Sooyoung Lee, Eunjae Cheon, Youngjoo Na, Kyu Jung Park, Eunjoo Lee A582 Validation of the Red Maple Trials Allergen Challenge Theatre for Ragweed Pollen Challenge William Yang, Suzanne Kelly, Rob Perrins, Jimmy Yang A583 Preliminary Evaluation of the Red Maple Trials Allergen Challenge Theatre for Grass Pollen William Yang, Suzanne Kelly, Rob Perrins, Jacob Karsh, Jimmy Yang A584 The Association Between Tobacco and the Risk of Asthma in Urban and Rural Children in San Francisco, Argentina Hector Badellino, Alvaro Teijeiro, Mabel Cuello, Marilyn Urrutia Pereira, Gustavo Egues A585 The Prevalence of Allergic Rhinitis in University Students in Manisa Ayse Aktas A586 Allergen Sensitization in Zimbabwean Children with Atopic Dermatitis Jin-Kyong Chun, Hilda Angela Mujuru, Elopy N Sibanda A587 Vitamin D Insufficiency in Asthmatic Patients Andreea Ioana Popescu, Raluca Greblescu A588 The Prevalence of Hypersensitivity Reactions Against Drugs Among University Students. Suheyla Rahman, Ayse Aktas A589 Sublingual Immunotherapy Among Problematic Patients, Suffering from Allergic Rhinitis. Nataly Tataurshchikova A590 A Novel Biomarker for Wheezing and Atopy in Early Infancy Eishika Dissanayake, Yuzaburo Inoue, Naoki Shimojo, Taiji Nakano A591 Prognostic Factors for Atopic Dermatitis in Spontaneously Born Babies from Low Socioeconomic Background Conny Tanjung A592 Higher IgE Antibody Levels Mediate Anti-Cancer Immunity in Transgenic KN1 Hyper-IgE Mice Erika Jensen-Jarolim, Judit Fazekas, Josef Singer, Anna Lukschal, Reinhard Horvat, Gertrude Achatz-Straussberger, Gernot Achatz A593 Fructooligosaccharides Intake during Pregnancy and Lactation Increases Gut Bifidobacterium and IL-27 in Breast Milk Yuji Fujita, Shuji Ikegami, Yoshitaka Nakamura, Yuzaburo Inoue, Naoki Shimojo, Yoichi Kohno, Shuichi Suzuki, Naoko Ozawa, Takayuki Kubota, Ken Nonaka, Osamu Ohara, Kentaro Masuda A594 Effect of Nintedanib on Asthma in Mouse Model Chin Kook Rhee, Sook Young Lee, Hwa Young Lee, Hea Yon Lee, Ji Young Kang, Sei Won Kim, Soon Seog Kwon, Young Kyoon Kim A595 Delayed Contrast Media Hypersensitivity after Coronary Angiography Gun-Woo Kim, Ju-Young Kim, Sang-Heon Cho, Hye-Ryun Kang, Hyo-Soo Kim, Jung Gyu Han, Jin Lee, Ji Young Lee, Ji Young Go, So Jung Park A596 Gene Expression Profiling in Patients with Chronic Idiopathic Urticaria Reveals Unique Gene Signature Distinct from Healthy Controls Julie Kim-Chang, Cassandra Love, Patricia Lugar A597 Failure to Recognize Lymphopenia in Newborn Leads to Undetectable Primary Immunodeficiency Endah Citraresmi A598 The Concordance Between Lung Function Test and Indonesian Version of Childhood Asthma Control Test (CACT) Nastiti Kaswandani, Cynthia Utami, Mardjanis Said A599 Synergistic Interaction Between Bronchiolitis and PM(10) Is Modified By IL-13 Polymorphism on Asthma Development: Replication from Cheer Study Young-Ho Jung, Song-I Yang, Byoung-Ju Kim, Ji-Won Kwon, Hwan-Cheol Kim, Jong-Han Leem, Ju-Hee Seo, Hyung Young Kim, So-Yeon Lee, Ho-Jang Kwon, Hyo-Bin Kim, Hyun-Ju Cho A600 The Transcription Factor Ehf Is Involved in TGF-b-Induced Suppression of Fceri and c-Kit Expression and Fceri-Mediated Activation in Mast Cells Susumu Yamazaki, Nobuhiro Nakano, Asuka Honjoh, Eisuke Inage, Yosuke Baba, Yoshikazu Ohtsuka, Toshiaki Shimizu A601 The Follow up of the Potential Immunosuppressant Effects of Marijuana (MJA) Ishaq M, Sameera MI Khan, Imran Khan, Sabeen Khan A602 Risk Factors of Allergen Sensitization at 3 Years: Results from the Gusto Study Evelyn Xiu Ling Loo, Anne Goh, Oon Hoe Teoh, Yiong Huak Chan, Seang Mei Saw, Kenneth Kwek, Peter D Gluckman, Keith M Godfrey, Hugo Van Bever, Yap Seng Chong, Bee Wah Lee, Lynette Shek, Alison Joanne Lee A603 IL-6 Blockade As a Steroid-Sparing Treatment for Rhupus Patients Daniela Rossi A604 Examination of Late Pulmonary Toxicity in Children Treated for Malignancies Agnes Nemeth A605 Technical Validation of the Repurposing of a Personal Particle Sampler to Determine House Dust Mite Exposure in the Ambient Air Torsten Sehlinger, Karl-Christian Bergmann, Frank Goergen A606 Zinc Deficiency in Children with Severe Atopic Dermatitis: More Common Than Generally Thought Mohammad S. Ehlayel, Abdul Bari Bener A607 Strong Association Between HLA-B*5801 Allele and Allopurinol – Induced Severe Cutaneous Adverse Reactions in Vietnamese Hieu Chi Chu, Nga Thi Quynh Do, Dinh Van Nguyen, Ha Thi Thu Nguyen, Huong Thi Minh Le, Sheryl Van Nunen, Christopher Vidal, Suran Fernando A608 Successful Rapid Desensitization to Glatiramer Acetate: Report of 2 Cases Fotis Psarros, Ekaterini Syrigou, Ekaterini Politi, Spyridon Chrysoulakis A609 Asthma Exacerbations Seasonal Variation in Two Perennial Phenotypes during Twenty Years (1995-2014): House Dust Mite Monosensitized and Non Atopic Patients Dimitrios Vourdas, Konstantinos Petalas A610 Occupational Allergy to Fungal Spores Among the Farmers of Paddy Fields in West Bengal, India: An Aeromycological and Immunological Approach Mouli SAHA, Kashinath Bhattacharya A611 Study of Efficacy of Sublingual Immunotherapy (SLIT) in Cases of Severe Persistent Allergic Rhinitis Subir Jain A612 Mesenchymal Stem Cells Suppress Lung Inflammation and Airway Remodeling in Chronic Asthma Rat Model Via PI3K/Akt Signaling Pathway Mesenchymal Stem Cells Suppress Lung Inflammation and Airway Remodeling in Chronic Asthma Rat Model Via PI3K/Akt Signaling Xiaolian Song, Haiyan Lin A613 Development of Allergen ELISA Kits for Dust Mites, Pollen, and Pet Dander Kyohei Nishikawa, Takashi Shimada, Hiroshi Yasueda, Tadao Enomoto, Daisuke Aizawa, Takayoshi Kobayashi A614 Yoga As a Lifestyle Modification to Improve the Quality of Life in Smokers with Allergic Rhinitis Chellaa R A615 Study of Incidence of Severe Persistent Allergic Rhinitis in Different Age Groups,Sex Prevalance and Type of Allergen” Aeroallergen or Food Allergen” Responsible for Severe Persistent Allergic Rhinitis in Central India Subir Jain A616 Causative Allergens in Cases of Severe Persistent Allergic Rhinitis in Central India Subir Jain A617 Atopic Dermatitis: A New Data on the Mechanisms of Chronic Pruritus Marina Yudina A618 The Efficacy and Safety of Peanut Oral Immunotherapy in High-Dose with Predicting Factors Ishaq M, Sameera MI Khan, Imran Khan, Sabeen Khan A619 Evaluation of Long-Term Prognosis and Topical Corticosteroid Usage after One Year of Proactive Treatment for Children with Moderate-to-Severe Atopic Dermatitis Mayako Saito A620 Allergy Symptoms in the First Two Months of Life Nurul Iman Nilam Sari A621 Factors Related to the Seasonal Variation of Allergic Rhinitis Jae Young Kim, Jaechul Song, Inah Kim, Kyeong Joon Lee, Soo Jin Park, Soo Yong Roh A622 Allergic Risk Survey in Lao Children at out-Patient Department, Children’s Hospital, Vientiane Capital, Lao PDR Somxay Billamay A623 Correlation Between Food Allergy, Aeroinhalant Allergy, Allergic Rhinitis, Atopic Dermatitis, and Acute Upper Respiratory Tract Infections and Levels of Severity of Asthma in Pediatric Medicine Department Saiful Anwar Hospital Indonesia Muchammad Fahrul Udin A624 Comparative Study of Pine, Oak, and Ginkgo Pollen Counts in Korea during Last Four Years Mae Ja Han, Jae-Won Oh, Kyu Rang Kim, Baek-Jo Kim A625 Effectiveness of Allergy-Test Directed Elimination Diets in Eosinophilic Esophagitis Jorge A Mazza, Jason Kangeun Ko, David JT Huang A626 Comparison of Cut-Off Values and Probability Curves for Egg Specific IgE in Diagnosis of Egg Allergy in Young Children Kanae Furuya, Keigo Kainuma, Takahiro Ito, Mizuho Nagao, Takao Fujisawa, Junya Hirayama, Yu Kuwahara A627 A Case of Persistent Atopic Dermatitis Associated with Parasitic Infection Rosanna Qualizza, Cristoforo Incorvaia, Anna Maraschini A628 Aeroallergenic Profile of Indoor Allergens and Their Clinical Relevance in Allergy and Asthma Patients in Saudi Arabia Syed Mohammed Hasnain, Abdulrahman Al-Frayh A629 Oral Exposure to the Amino Acid Glycine Inhibits the Onset of Allergic Disorders Anita Hartog, Jacqueline Bastiaans, Reinilde Loonstra, Lieke Rutten, Lucien Harthoorn, Jeroen Van Bergenhenegouwen, Johan Garssen, Johan Garssen A630 Cough As a Key Symptom in Asthma, Allergic Rhinitis, COPD and Rhinosinusitis and Its Impact in Korea Kwang-Ha Yoo, Sang-Heon Cho, AG Ghoshal, Abdul Razak Bin Abdul Muttalif, Horng- Chyuan Lin, Sanguansak Thanaviratananich, Shalini Bagga, Rab Faruqi, Santwona Baidya, Colman Taylor, De Yun Wang, Hae-Ryun Ahn, Soon-Kwan Hong, Jong-Woong Kim, Gui-Hyun Nam, Mee-Ja Kim, Jae-Kyoung Park A631 Cysteine Protease Allergen Def f 1 Induces Th2 Cytokines in Mouse Bone Marrow Derived Basophils Via ERK and JNK Dependent Pathways Myung-Hee Yi, Kyoung Yong Jeong, Ju-Yeong Kim, Tai-Soon Yong A632 Novel Multiple Allergy Testing Kit Using Parallel Lines Array (PLA) Technology Bum Joon Kim, Hs Joo, Kj Lim, Jae-Hyun Lee, Jung-Won Park, Kh Yoon, DS Choi A633 Quantitative Rapid Kit for Human Immunoglobulin Hanseung Joo, Bum Joon Kim, Kj Lim, MJ KIM, DS Choi, Kh Yoon A634 Total IgE Measurement By Protia Allergy-Q: Comparison Study with Immunocap Bum Joon Kim, Hanseung Joo, Woo Sang Jung, Kj Lim, DS Choi A635 Prevalence and Risk Factors of Asthma Among Korean Farmers Ji-Hoon Lee, Soon-Chan Kwon, Soo-Jin Lee, Soo Yong Roh, Hogil Kim, Kyeong Joon Lee A636 Dietary Intake and Perceived Immune Status in Young Dutch Women Aurora Van De Loo, Amanda Fernstrand, Johan Garssen, Joris Verster A637 The Effects of Antihistamine Drugs on on-Road Driving Performance Aurora Van De Loo, Johan Garssen, Joris Verster A638 Grass Is Guilty: A Case of Anaphylactic Shock and Asthmatic Status in the Same Time in an Individual Jasmina Golez A639 Cyclic Gamp-AMP(cGAMP) Induces Allergic Inflammation Koji Ozasa, Etsushi Kuroda, Ken Ishii, Ken Ishii A640 Role of Omalizumab in the Setting of Recalcitrate Dermatitis with Extremely Elevated IgE Levels Muhammad Imran, Selina Gierer, John Martinez A641 Follow-up Study on the Natural History of Prawn Allergy Lydia Wong, Bee Wah Lee, Gaik Chin Yap, Genevieve Llanora, Bernard Thong, Lynette Shek A642 Protein-Losing Dermopathy Impairing Growth in Children with Severe Atopic Dermatitis Mohammad S. Ehlayel, Ashraf Soliman A643 Airways Assessment of Aged Nursing Homes Residents Pedro Martins, João Marques, Joana Gomes-Belo, Teresa Palmeiro, Iolanda Caires, Joana Belo, Maria Amália Botelho, Paula Leiria-Pinto, Nuno Neuparth A644 Use of Skin Prick Test, Specific IgE to Shrimp and Rpen a1 to Determine Clinical Reaction to Shrimp in Area with High Prevalence of House Dust Mite Sensitization Narissara Suratannon, Jaichat Mekaroonkamol, Jarungchit Ngamphaiboon, Piyawadee Lertchanaruengrith, Pantipa Chatchatee A645 Identification of Specific IgE-Binding Proteins in Tree of Heaven (Ailanthus altissima) Pollen Gholamali Kardar, Ahmad Majd, Youcef Shahali, Farrokh Ghahremaninejad, Zahra Pourpak, Fateme Mousavi A646 Allergy Immunotherapy Well Tolerated in Children Mahnaz Sadeghi-Shabestari A647 Steinert (DM1) Patients Have IgG1 Deficiency and Should be Screened for Immune Deficiency K. Van Bilsen, O. Manusama, W.a. Dik, M. Van Der Burg, V. H. J. Van Der Velden, V.a.S. H. Dalm, P. M. Van Hagen A648 The Change of Serous Sige and Three Evaluation before and after Sublingual Immunotherapy with Dermatophagoides Farinae for Persistent Allergic Rhinitis Yongping Liu A649 Garlic Extracts Reduce Histamine-Induced Proliferation and Migration of Human Asthmatic Bronchial Smooth Muscle Cells Yi Yeong Jeong A650 A Case of Occupational Contact Dermatitis Caused By N-Acetylcysteine Ji Hye Kim, Moon Gyeong Yoon, Young Min Ye, Yoo Seob Shin, Ga Young Ban, Hae-Sim Park, Hye Min Jung A651 The Association Between Pollen Change and Asthma Attacks Soo Yong Roh, Jaechul Song, Ji-Hoon Lee, Hogil Kim, Jae Young Kim, Kyeong Joon Lee A652 Incidence of Emergency Department Visits and Hospitalizations for Asthma Exacerbations during the Lunar Month in Singapore Lydia Wong, Mohana Rajakulendran, Haripriya Santhanam, Lynette Shek, Tow Keang Lim A653 The Prevalence of Positive Reaction for Skin Prick Test in Korean Farmers and Its Occupational Risk Factors Hogil Kim, Soo-Jin Lee, Ji-Hoon Lee, Soo Yong Roh, Soon-Chan Kwon A654 Drug Allergy in Children: A Three-Years Experience at Dr. Kariadi Hospital Semarang Indonesia Wistiani, Galuh H, Ani Wistiani A655 The Identification of Morphology, Structure and Study of Seasonal Variation of Airborne Fraxinus Excelsior Pollen Grains in the Tehran Gholam Ali Kardar, Maryam Sharifshoushtari, Ahmad Majd, Taher Nejadsattari, Zahra Pourpak, Mostafa Moin A656 Sublingual Immunotherapy in Elderly Rhinitis Patients Sensitized to House Dust Mites Ji Hye Kim, Daehong Seo, Young Min Ye, Hae-Sim Park, Jung-Won Park, Jae-Hyun Lee, Yoo Seob Shin A657 Healthy Ageing Research Center (HARC) As a Platform for Multidisciplinary Approaches to Respiratory Research in the Elderly Marek L. Kowalski, Aleksandra Wardzynska, Marcin Kurowski, Malgorzata / Ewa Pawelczyk, Adam Wysokinski, Iwona Kloszewska, Janina Grzegorczyk, Wojciech Piotrowski, Joanna Makowska A658 Estimation of Cases of Work-Related Asthma Using Capture-Recapture Methods Soon-Chan Kwon, Jaechul Song, Yong-Kyu Kim A659 Primary School Students’ Parents Reported ISAAC Questionnaire in a Low Income Area of Ankara Ilknur Bostanci, Zeynep Sengul Emeksiz, Aysegul Ertugrul, Serap Ozmen, Soner Sahin A660 Usefulness of PC20 Adenosine Monophosphate in Diagnosis and Treatment in Bronchial Asthma Sang-Ha Kim, Myoung Kyu Lee, Won Yeon Lee, Suk Joong Yong, Seok Jeong Lee, Ye-Ryung Jung A661 S100 Calcium Binding Protein A9 in Sputum of Patients with Steroid Naive Asthma: Relation with Airway Obstruction and Nneutrophilc Inflammation Myung Shin Kim, Jong-Sook Park, An-Soo Jang, Choon-Sik Park A662 Risk Factor Asthma in Pediatric Pneumonia Patients Diah Asri Wulandari, Cissy Kartasasmita A663 Prevalence and Risk Factors of Childhood Asthma and Allergic Disease at Exposed Area By Emission of Cement Padang Factory Finny Fitry Yani, Rizanda Machmud, Dhina Lydia Lestari A664 Association Between Serum Level of 25-Hydroxyvitamin D with Atopic Dermatitis Occurrence and Severity in Children Rusdi Rusdi, Yurmalina Yurmalina, Eryati Darwin A665 Thiol-Disulfide Balance in Children with Atopic Dermatitis Ilknur Bostanci, Gulin Karacan, Nazli Ercan, Asuman Colak, Murat Alisik, Gulay Basarir, Ozcan Erel A666 Recurrent Mouth Ulsers Caused By Braces after Developing a Nickel Allergy in Children Ilknur Bostanci, Yasemin Keskin A667 Anaphylactic Reaction to Famotidine with Pheniramine Hypersensitivity Ilkay Koca Kalkan A668 Novel Transcriptomic and Immunoproteotomic Approaches in Identifying Cross-Reactive Allergens Between Crustacean and Molluscs Andreas/Ludwig Lopata, Kyall Zenger, Roni Nugraha, Sandip Kamath A669 Pollen Season and Climate Change in the Continental United States (CONUS) Leonard Bielory, Panos Georgopoulos, Yong Zhang, Wheat Mi, Ting Cai A670 Differences of Change in Der p IgG4 and CD4+CD25+FoxP3+ Treg Cells Between Sublingual and Subcutaneous Immunotherapy with House Dust Mite in Chinese Patients with Allergic Rhinitis MO Xian, Jing Li, Mulin Feng",2016 Apr 19,"['Lee, Heung-Man', 'Park, Il-Ho', 'Shin, Jae-Min', 'Yoon, Hyun-Sun', 'Park, Gyeong Yul', 'Zeher, Margit', 'Matsui, Katsuhiko', 'Tamai, Saki', 'Ikeda, Reiko', 'Suri, Drsushil', 'Suri, Dranu', 'Arani, Marzieh Heidarzadeh', 'Lubis, Azwin', 'Endaryanto, Anang', 'Koga, Shinichiro', 'Suk, Lee Ju', 'Tsuzuki, Yasunobu', 'Kim, Seo Hyeong', 'Shin, Jung U.', 'Noh, Ji Yeon', 'Jin, Shan', 'Jin, Shan', 'Lee, Hemin', 'Lee, Jungsoo', 'Park, Chang Ook', 'Lee, Kwang Hoon', 'Lee, Kwang Hoon', 'Tepetam, Fatma Merve', 'Park, Chun Wook', 'Son, Jee Hee', 'Cho, Soo Ick', 'Cho, Yong Se', 'Byun, Yun Sun', 'Yang, Yoon Seok', 'Chung, Bo Young', 'Kim, Hye One', 'Cho, Hee Jin', 'Katada, Yoshinori', 'Tanaka, Toshio', 'Nakabayashi, Akihiko', 'Nishida, Koji', 'Aoyagi, Kenichi', 'Tsukamoto, Yuki', 'Konma, Kazushi', 'Matsuura, Motoo', 'Park, Jung-Won', 'Harada, Yoshinori', 'Jeong, Kyoung Yong', 'Yura, Akiko', 'Yoshimura, Maiko', 'Kyung, Tae-Suk', 'Kim, Young Hyo', 'Park, Chang-Shin', 'Jang, Tae Young', 'Heo, Min-Jeong', 'Jung, Ah-Yeoun', 'Yang, Seung-Chan', 'Kim, Hye One', 'Cho, Yong Se', 'Byun, Yun Sun', 'Yang, Yoon Seok', 'Chung, Bo Young', 'Son, Jee Hee', 'Park, Chun Wook', 'Cho, Hee Jin', 'Pfaar, Oliver', 'Sager, Angelika', 'Agarwal, Amit', 'Singh, Meenu', 'Chatterjee, Bishnupda', 'Chauhan, Anil', 'Striz, Ilja', 'Cecrdlova, Eva', 'Petrickova, Katerina', 'Kolesar, Libor', 'Sekerkova, Alena', 'Svachova, Veronika', 'Petricek, Miroslav', 'Kwon, Hyuck Hoon', 'Kim, Kyu Han', 'Kumar, Suman', 'Manzon, Lou Ver Leigh Arciaga', 'Andaya, Pilar Agnes Gonzalez', 'Lew, Bark-Lynn', 'Oh, Youngjun', 'Suh, Dongwoo', 'Sim, Woo-Young', 'Jeong, Kyoung Yong', 'Yi, Myung-Hee', 'Son, Mina', 'Lyu, Dongpyo', 'Lee, Jae-Hyun', 'Yong, Tai-Soon', 'Hong, Chein-Soo', 'Park, Jung-Won', 'Jeong, Kyoung Yong', 'Yi, Myung-Hee', 'Son, Mina', 'Lyu, Dongpyo', 'Lee, Jae-Hyun', 'Yong, Tai-Soon', 'Hong, Chein-Soo', 'Park, Jung-Won', 'Siavashi, Mohammadreza', 'Yun, Hey Suk', 'Kang, Ha-Na', 'Oh, Jae-Won', 'Choi, Young Jin', 'Oh, Jae-Won', 'Choi, Young Jin', 'Kang, Ha-Na', 'Sentsova, Tatiana', 'Vorozhko, Ilya', 'Chernyak, Olga', 'Revyakina, Vera', 'Timopheeva, Anna', 'Donnikov, Andrey', 'Sentsova, Tatiana', 'Vorozhko, Ilya', 'Chernyak, Olga', 'Revyakina, Vera', 'Timopheeva, Anna', 'Lee, Ji Hyun', 'Park, Young Min', 'Choi, Sang Soo', 'Han, Kyung Do', 'Jung, Han Mi', 'Youn, Young Hoon', 'Lee, Jun Young', 'Park, Yong Gyu', 'Lee, Seung-Hwan', 'Li, Jing', 'Feng, Mulin', 'Roponen, Marjut', 'Schaub, Bianca', 'Wong, Gary W. K.', 'Yang, Zhaowei', 'Choi, Young Jin', 'Kang, Ha-Na', 'Oh, Jae-Won', 'Sun, Baoqing', 'Zheng, Peiyan', 'Park, Yoon-Sung', 'Son, Sang Wook', 'Kose, Sukran', 'Kiraz, Kemal', 'Yalcin, Arzu Didem', 'Yune, Sehyo', 'Paeng, Jae-Won', 'Oh, Mi-Jung', 'Lee, Byung-Jae', 'Choi, Dong-Chull', 'Lim, Young Hee', 'Ha, Kyoung Won', 'Lee, Jin-Young', 'Yamamoto-Hanada, Kiwako', 'Narita, Masami', 'Futamura, Masaki', 'Ohya, Yukihiro', 'Kim, Jihyun', 'Choi, Jinwha', 'Kim, Kwanghoon', 'Choi, Jaehee', 'Ahn, Kangmo', 'Chang, Sun-Ho/Brian', 'Li, Lisha', 'Adachi, Yu-Ichi', 'Kanatani, Kumiko Tsuji', 'Narabayashi, Shigeyuki', 'Okafuji, Ikuo', 'Tanaka, Yuya', 'Tsuruta, Satoru', 'Takamatsu, Nobue', 'Kim, Soo Whan', 'Kim, Do Hyun', 'Yoon, Jong-Seo', 'Kim, Jin Tack', 'Kim, Hwan Soo', 'Chun, Yoon Hong', 'Kim, Hyun Hee', 'Won, Sul Mui', 'Hon, Kam Lun E.', 'Chow, Chung Mo', 'Leung, Ting Fan', 'Kim, Do Hyun', 'Kim, Soo Whan', 'Esguerra, Gemmalyn', 'Resurreccion, Emily', 'Kionisala, Kristine Elisa', 'Dela Cruz, Jenni Rose', 'Imran, Muhammad', 'Choe, Yun Seon', 'Kim, Kyu Han', 'Choi, Mira', 'Kim, Byung Soo', 'Lee, Hyun-Joo', 'Kim, Jeong-Min', 'Kim, Jeong-Min', 'Kim, Gun-Wook', 'Mun, Je-Ho', 'Mun, Je-Ho', 'Kim, Hoon-Soo', 'Song, Margaret', 'Ko, Hyun-Chang', 'Ko, Hyun-Chang', 'Kim, Moon-Bum', 'Yoon, Sun-Young', 'Kandhare, Amit', 'Yahiro, Noriko', 'Agarwal, Amit', 'Singh, Meenu', 'Kaur, Jasleen', 'Pawankar, Ruby', 'Pant, Pankaj', 'Singh, Sukhmanjeet', 'Kim, Hwan Soo', 'Yoon, Jong-Seo', 'Won, Sul Mui', 'Chun, Yoon Hong', 'Kim, Jin Tack', 'Kim, Hyun Hee', 'Kim, Hwan Soo', 'Won, Sul Mui', 'Chun, Yoon Hong', 'Yoon, Jong-Seo', 'Kim, Hyun Hee', 'Kim, Jin Tack', 'Kampitak, Thatchai', 'Kim, So Min', 'Lee, Hyun Joo', 'Kim, Hei Sung', 'Lee, Jeong Deuk', 'Cho, Sang Hyun', 'Godse, Kiran', 'Soekarno, Juwita', 'Ratnasari, Sarie', 'Datau, E. Alwi', 'Surachmanto, Eko', 'Matheos, JC', 'Leung, Ting Fan', 'Kwok, Jamie Sui-Lam', 'Tung, Christine Kit-Ching', 'Tang, Man Fung', 'Tsui, Stephen Kwok-Wing', 'Wong, Gary WK', 'Hon, Kam Lun Ellis', 'Tam, Wing Hung', 'Sy, Hing Yee', 'Lee, Sohee', 'Shin, Hyun-Woo', 'Lee, Mingyu', 'Kim, Dae Woo', 'Khalmuratova, Roza', 'Kim, Mi Yeoung', 'Jeong, Jaewon', 'Park, Chansun', 'Wai, Christine Yee Yan', 'Leung, Patrick S. C.', 'Leung, Nicki Y. H.', 'Chu, Ka Hou', 'Lee, Hee Seon', 'Lee, Kyung Eun', 'Hong, Jung Yeon', 'Kim, Mi Na', 'Kim, Min Jung', 'Kim, Yoon Hee', 'Sol, In Suk', 'Yoon, Seo Hee', 'Kim, Kyung Won', 'Sohn, Myung Hyun', 'Kim, Kyu-Earn', 'Kim, Ji Hye', 'Park, Hae-Sim', 'Shin, Yoo Seob', 'Ye, Young Min', 'Seo, Daehong', 'Yoon, Moon Gyeong', 'Lee, Young Mok', 'Seo, Daehong', 'Kim, Ji Hye', 'Lee, Young-Mok', 'Ye, Young Min', 'Park, Hae-Sim', 'Ban, Ga Young', 'Cho, Kumsun', 'Kim, Seung-Hyun', 'Kwon, Yong Eun', 'Yoon, Moon Gyeong', 'Kim, Ji Hye', 'Shin, Yoo Seob', 'Ye, Young Min', 'Nahm, Dong-Ho', 'Park, Hae-Sim', 'Andaya, Pilar Agnes Gonzalez', 'Andaya, Pilar Agnes Gonzalez', 'Ban, Ga Young', 'Jung, Chang Gyu', 'Lee, Seung-Ihm', 'Le Pham, Duy', 'Suh, Dong-Hyeon', 'Yang, Eun-Mi', 'Ye, Young Min', 'Shin, Yoo Seob', 'Park, Hae-Sim', 'Wang, Wan Jun', 'Xian, MO', 'Xie, Yan Qing', 'Zheng, Jing Ping', 'Li, Jing', 'Savilahti, Emma Merike', 'Mäkitie, Outi', 'Kukkonen, Anna Kaarina', 'Andersson, Sture', 'Viljakainen, Heli', 'Savilahti, Erkki', 'Kuitunen, Mikael', 'Godse, Kiran', 'Le Pham, Duy', 'Ban, Ga Young', 'Kim, Seung-Hyun', 'Yang, Eun-Mi', 'Park, Hae-Sim', 'Lee, Ji-Ho', 'Chwae, Yong-Joon', 'Chin, Li-Ming', 'Shieh, Chi-Chang', 'Kim, Ji Hye', 'Yoo, Hye-Soo', 'Yoon, Moon Gyeong', 'Ban, Ga Young', 'Ban, Ga Young', 'Shin, Yoo Seob', 'Ye, Young Min', 'Park, Hae-Sim', 'Sung, Myong Soon', 'Choi, Jin Uck', 'Kim, Sung Won', 'Hwang, Yong Jin', 'Park, Arum', 'Lee, Eun', 'Yang, Song-I', 'Cho, Hyun-Ju', 'Yu, Jinho', 'Lee, Dong Hun', 'Kim, Eun Ju', 'Kim, Yeon Kyung', 'Doh, Eun Jin', 'Eun, Hee Chul', 'Chung, Jin Ho', 'Lee, Young Mee', 'Jin, Seon Pil', 'Li, Xingnan', 'Kaminski, Naftali', 'Wenzel, Sally', 'Bleecker, Eugene', 'Meyers, Deborah', 'Huasong, Zeng', 'Mo, Ji-Hun', 'Samivel, Ramachandran', 'Kim, Eun-Hee', 'Kim, Ji-Hye', 'Bae, Jun-Sang', 'Chung, Young-Jun', 'Kim, Dae Woo', 'Lee, Eun', 'Lee, Si Hyeon', 'Kim, Young-Ho', 'Cho, Hyun-Ju', 'Yu, Ho-Sung', 'Kang, Mi-Jin', 'Yang, Song-I', 'Jung, Young-Ho', 'Kim, Hyung Young', 'Seo, Ju-Hee', 'Kim, Byoung-Ju', 'Kim, Hyo-Bin', 'Lee, So-Yeon', 'Kwon, Ho-Jang', 'Hong, Soo-Jong', 'Palikhe, Sailesh', 'Park, Hae-Sim', 'Kim, Seung-Hyun', 'Kim, Ji Hye', 'Yang, Eun-Mi', 'Sibunruang, Suda', 'Klaewsongkram, Jettanong', 'Sentsova, Tatiana', 'Vorozhko, Ilya', 'Timopheeva, Anna', 'Chernyak, Olga', 'Revyakina, Vera', 'Sokolnikov, Andrey', 'Nisihino, Makoto', 'Okada, Yu', 'Yanagida, Noriyuki', 'Ebisawa, Motohiro', 'Sato, Sakura', 'Ogura, Kiyotake', 'Asaumi, Tomoyuki', 'Nagakura, Kenichi', 'Manabe, Tetsuharu', 'Unno, Hirotoshi', 'Rodrigues, Pedro M.', 'Schrama, Denise', 'Mohamed, Gadija', 'Hüsselmann, Lizex', 'Hüsselmann, Lizex', 'Ndimba, Bongani', 'Shim, Jae-Uoong', 'Koh, Young Il', 'Rhee, Joon Haeng', 'Jeong, Ji-Ung', 'Van Nguyen, Dinh', 'Chu, Hieu Chi', 'Tran, Mui Thi', 'Vidal, Christopher', 'Fernando, Suran', 'Van Nunen, Sheryl', 'Van Than, Sy', 'Feng, Mulin', 'Li, Jing', 'Kim, Dong-Kyu', 'Hong, Seung-No', 'Eun, Kyoung Mi', 'Jin, Hong Ryul', 'Kim, Dae Woo', 'Bao, Jun', 'Bao, Yi-Xiao', 'Podder, Sanjoy', 'Kumar, Goutam', 'Dutta, Shampa', 'Ghosh, Amlan', 'Saha, Goutam Kumar', 'Podder, Sanjoy', 'Gupta, Salil Kumar', 'Trinh, Tu/Hoang Kim', 'Shin, Yoo Seob', 'Park, Hae-Sim', 'Liu, Jing-Nan', 'Le Pham, Duy', 'Ko, Hyun-Chang', 'Kim, Byung Soo', 'Kim, Moon-Bum', 'Özbudak, Ömer', 'Üzer, Fatih', 'Al-Ahmad, Mona', 'Alowayesh, Maryam', 'Carroll, Norman', 'Singh, Anand Bahadur', 'Pérez-Llano, Yordanis', 'Lorenzo, María Del Carmen Luzardo', 'González, Wendy Ramírez', 'Cruz, Carlos Calcines', 'Quintana, Rady Laborde', 'Morejón, Alain', 'Bourg, Virgilio', 'Stoker, Marilé Hechavarría', 'Bae, Jun-Sang', 'Samivel, Ramachandran', 'Kim, Eun-Hee', 'Kim, Ji-Hye', 'Mo, Ji-Hun', 'Hanaoka, Keiko', 'Hide, Michihiro', 'Tanaka, Akio', 'Hiragun, Makiko', 'Kawai, Mikio', 'Kim, Kwanghoon', 'Kim, Hye-Young', 'Kim, Jihyun', 'Ahn, Kangmo', 'Han, Youngshin', 'Kim, Gun-Wook', 'Ko, Hyun-Chang', 'Kim, Byung Soo', 'Kim, Moon-Bum', 'Song, Margaret', 'Matsubara, Takeshi', 'Iwamoto, Hiroshi', 'Nakazato, Yuki', 'Namba, Kazuyoshi', 'Takeda, Yasuhiro', 'Lee, Jae Hoon', 'Bae, Woo Yong', 'De Schryver, Els', 'Calus, Lien', 'Gevaert, Philippe', 'Van Zele, Thibaut', 'Bachert, Claus', 'Mori, Akio', 'Kouyama, Satoshi', 'Yamaguchi, Miyako', 'Iijima, Yo', 'Abe-Ohtomo, Akemi', 'Hayashi, Hiroaki', 'Watai, Kentaroh', 'Mitsui, Chihiro', 'Oshikata, Chiyako', 'Sekiya, Kiyoshi', 'Tsuburai, Takahiro', 'Ohtomo, Mamoru', 'Fukutomi, Yuma', 'Taniguchi, Masami', 'Kang, Ju Wan', 'Kim, Jeong Hong', 'Kim, Jeong Hong', 'Lee, Keun-Hwa', 'Lee, Hye-Sook', 'Hong, Seong-Chul', 'Lee, Jaechun', 'Seo, Ji Won', 'Lee, Jae Hoon', 'Bae, Woo Yong', 'Kuznecovs, Ivans Sergejs', 'Kuznecova, Galina', 'Bergmann, Karl-Christian', 'Zuberbier, Torsten', 'Salame, Joseph', 'Sehlinger, Torsten', 'Bölke, Georg', 'Kim, Yoo Suk', 'Chang, Jung Hyun', 'Kim, Jeong Hong', 'Kang, Ju Wan', 'Hong, Seung-No', 'Han, Doo Hee', 'Rhee, Chae-Seo', 'Ko, Young-Joo', 'Kim, Young Hyo', 'Kim, Dae-Young', 'Jang, Tae Young', 'Yokooji, Tomoharu', 'Hirano, Taiki', 'Matsuo, Hiroaki', 'Kuznecova, Galina', 'Kuznecovs, Ivans Sergejs', 'Wani, Roohi Rasool', 'Syed, Shafia Alam', 'Hassan, Ghulam', 'Gul, Ayaz', 'Nissar, Saniya', 'Shah, Zaffar Amin', 'Pereira, Marilyn Urrutia', 'Fernandez, Carmen', 'Sole, Dirceu', 'Neto, Herberto Jose Chong', 'Acosta, Veronica', 'Cepeda, Alfonso Mario', 'Castello, Mirta Alvarez', 'Almendarez, Claudia', 'Saenz, Jose Santos Lozano', 'Sisul, Juan C.', 'Filho, Nelson Rosario', 'Castillo, Antonio', 'Rostan, Marylin Valentin', 'Avila, Jennifer', 'Badellino, Hector', 'Manotas, Maria Carolina', 'Almarales, Raúl Lázaro Castro', 'León, Mayda González', 'Kim, Woo Kyung', 'Yoon, Hae-Sun', 'Kobayashi, Takehito', 'Noguchi, Tooru', 'Soma, Tomoyuki', 'Nakagome, Kazuyuki', 'Nakamoto, Hidetomo', 'Kita, Hirohito', 'Nagata, Makoto', 'Pereira, Marilyn Urrutia', 'Sole, Dirceu', 'Neto, Herberto Jose Chong', 'Cepeda, Alfonso Mario', 'Almarales, Raúl Lázaro Castro', 'Sisul, Juan C.', 'Rostan, Marylin Valentin', 'Badellino, Hector', 'Avalos, Miguel Alejandro Medina', 'Castillo, Antonio', 'Almendarez, Claudia', 'Filho, Nelson Rosario', 'Silot, Caridad Sanchez', 'Avila, Jennifer', 'Rodriguez, Felicia Berroa', 'Saenz, Jose Santos Lozano', 'Castello, Mirta Alvarez', 'Fernandez, Carmen', 'Soh, Wai Tuck', 'Jacquet, Alain', 'Ruxrungtham, Kiat', 'Nony, Emmanuel', 'Le Mignon, Maxime', 'Lee-Wong, Mary', 'McClelland, Suzanne', 'McClelland, Suzanne', 'Silverberg, Nanette B.', 'Song, Christian E.', 'Yang, Zhaowei', 'Zhang, Jiukai', 'Zheng, Wentao', 'Zhong, Nanshan', 'Li, Jing', 'Bae, Jung Ho', 'Cho, Young Joo', 'Kim, Joo Yeon', 'Vourdas, Dimitrios', 'Grigoreas, Christos', 'Petalas, Konstantinos', 'Zhang, Yuan', 'Shin, Seung-Heon', 'Ye, Mi-Kyung', 'Kim, Jeong-Kyu', 'Feng, Yong', 'Shang, Yunxiao', 'Seo, Sungchul', 'Choung, Ji Tae', 'Kim, Dohyeong', 'Yoo, Young', 'Lim, Hyunwook', 'Zhu, Wenjing', 'Liu, Chuanhe', 'Sha, Li', 'Chang, Li', 'Zhao, Min', 'Zhao, Linqing', 'Qian, Yuan', 'Chen, Yuzhi', 'Kim, Min-Hye', 'Cho, Young Joo', 'Rho, Mina', 'Kim, Jung-Won', 'Kang, Yeon-Mi', 'Yum, Kyung-Eun', 'Choi, Hyeon-Il', 'Choi, Jun-Pyo', 'Park, Han-Ki', 'Min, Taek-Ki', 'Pyun, Bok-Yang', 'Kim, Yoon-Keun', 'Wang, Xueyan', 'Kim, Woo Kyung', 'Nam, Yu Ran', 'Nam, Joo Hyun', 'Kim, Jung-Won', 'Kim, Min-Hye', 'Rho, Mina', 'Kang, Yeon-Mi', 'Yum, Kyung-Eun', 'Choi, Hyeon-Il', 'Choi, Jun-Pyo', 'Park, Han-Ki', 'Min, Taek-Ki', 'Cho, Young Joo', 'Pyun, Bok-Yang', 'Kim, Yoon-Keun', 'Narita, Hiroshi', 'Hirose, Junko', 'Kizu, Kumiko', 'Matsunaga, Ayu', 'Li, Jingyun', 'Zhang, Yuan', 'Zhang, Luo', 'Choi, Yean Jung', 'Shin, Hye Lim', 'Yang, Song-I', 'Lee, So-Yeon', 'Kwon, Sung-Ok', 'Jung, Young-Ho', 'Kwon, Ji-Won', 'Kim, Hyung Young', 'Seo, Ju-Hee', 'Kim, Byoung-Ju', 'Kim, Hyo-Bin', 'Oh, Se-Young', 'Kwon, Ho-Jang', 'Lee, Eun', 'Kang, Mi-Jin', 'Hong, Soo-Jong', 'Lee, Yun-Jeong', 'Kim, Joonil', 'Choi, Joon Young', 'Kang, Ji Young', 'Kim, Seok Chan', 'Kim, Sei Won', 'Kim, Seung Joon', 'Kim, Young Kyoon', 'Rhee, Chin Kook', 'Lee, Hea Yon', 'Lee, Hwa Young', 'Lee, Sook Young', 'Koh, Tae Kyung', 'Kim, Sung Wan', 'Lee, Kun Hee', 'Kwon, Chul', 'Jo, Joong-Saeng', 'Dong, Sung-Hwa', 'Byun, Young Seok', 'Song, Charles', 'Kang, Ji Young', 'Lee, Hwa Young', 'Kim, In Kyoung', 'Kim, Sei Won', 'Rhee, Chin Kook', 'Kim, Seung Joon', 'Kim, Seok Chan', 'Lee, Sook Young', 'Kim, Young Kyoon', 'Kwon, Soon Seog', 'Choi, Joon Young', 'Park, Pona', 'Jin, Hong Ryul', 'Kim, Dong-Kyu', 'Kim, Dae Woo', 'Hogenkamp, Astrid', 'Knippels, Leon', 'Van Esch, Betty C.a.m.', 'Van Bilsen, Jolanda', 'Jeurink, Prescilla V.', 'Gros, Marjan', 'Garssen, Johan', 'Smit, Joost J.', 'Pieters, Raymond H. H.', 'Kim, Boo-Young', 'Kim, Soo Whan', 'Lleonart, Ramon', 'Lay, Christophe', 'Benamor, Kaouther', 'Chen, Chua Mei', 'Knol, Jan', 'Chew, Charmaine', 'Chongsrisawat, Voranush', 'Goh, Anne', 'Chiang, Wen Chin', 'Rao, Rajeshwar', 'Chaithongwongwatthana, Surasith', 'Khemapech, Nipon', 'Yhi, Ji Young', 'Kim, Sang-Heon', 'Park, Dong Won', 'Moon, Ji-Yong', 'Kim, Tae Hyung', 'Sohn, Jang Won', 'Shin, Dong Ho', 'Yoon, Ho Joo', 'Cho, Seok Hyun', 'Kim, Sang-Heon', 'Moon, Ji-Yong', 'Lee, Jae-Hyun', 'Ban, Ga Young', 'Kim, Sujeong', 'Kim, Mi-Ae', 'Kim, Joo-Hee', 'Kim, Min-Hye', 'Park, Chan-Sun', 'Kwon, Hyouk-Soo', 'Kwon, Jae-Woo', 'Jung, Jae Woo', 'Kang, Hye-Ryun', 'Park, Jong-Sook', 'Kim, Tae-Bum', 'Park, Heung Woo', 'Cho, You Sook', 'Yoo, Kwang-Ha', 'Oh, Yeon-Mok', 'Lee, Sang-Rok', 'Julge, Kaja', 'Vasar, Maire', 'Vasar, Maire', 'Voor, Tiia', 'Rebane, Tiina', 'Kim, Yu Jin', 'Lee, Sang Min', 'Kang, Shin Myung', 'Kim, Sojeong', 'Kyung, Sun Young', 'Jeong, Sung Hwan', 'Park, Jeong-Woong', 'Hwang, Hyunjung', 'Seon, Yong Han', 'Park, Sanghui', 'Lee, Sang Pyo', 'Iordache, Marius', 'Jeong, Yeongsang', 'Eun, Sohee', 'Choi, Byung Min', 'Choung, Ji Tae', 'Seo, Wonhee', 'Zhang, Liang', 'Pawankar, Ruby', 'Nonaka, Manabu', 'Hayashi, Miyuki', 'Yamanishi, Shingo', 'Suzaki, Harumi', 'Itoh, Yasuhiko', 'Watanabe, So', 'Kobayashi, Hitome', 'Zotter, Zsuzsanna', 'Farkas, Henriette', 'Varga, Lilian', 'Veszeli, Nora', 'Imreh, Eva', 'Kovacs, Gabor', 'Nallbani, Marsel', 'Zheleznov, Semen', 'Urzhumtseva, Galina', 'Petrova, Natalia', 'Sarsaniia, Zhanna', 'Didkovskii, Nikolai', 'Zuberbier, Torsten', 'Gerdabi, Nader Dashti', 'Khodadadi, Ali', 'Abdoli, Zahra', 'Ghafourian, Mehri', 'Assarehzadegan, Mohammad Ali', 'Ghorban, Khodayar', 'Kim, Hyo-Bin', 'Zhou, Hui', 'Kim, Jeong Hee', 'Habre, Rima', 'Bastain, Theresa', 'Gilliland, Frank', 'Bae, Jong-Wook', 'Han, Kyu-Hyung', 'Jee, Young-Koo', 'Choi, Misoo', 'Hong, Seung-Phil', 'Kim, Seung-Hyun', 'Kim, Hee-Kyoo', 'Choi, Gil-Soon', 'Heo, Jeonghoon', 'Kim, Young-Ho', 'Park, Eun-Kee', 'Inoue, Takashi', 'Ogura, Kiyotake', 'Yanagida, Noriyuki', 'Unno, Hirotoshi', 'Nagakura, Kenichi', 'Manabe, Tetsuharu', 'Asaumi, Tomoyuki', 'Sato, Sakura', 'Okada, Yu', 'Ebisawa, Motohiro', 'Kim, Min-Gu', 'Cho, You Sook', 'Kim, Tae-Bum', 'Moon, Hee-Bom', 'Kim, Jung-Hyun', 'Kim, Hyo-Jung', 'Park, So-Young', 'Seo, Bomi', 'Kwon, Hyouk-Soo', 'Lee, Jaemoon', 'Lee, Taehoon', 'Yoo, Hye-Soo', 'Kim, Jieun', 'Kim, Inok', 'Kim, Haejin', 'Chang, Younhee', 'Park, Hae-Sim', 'Lee, Sooyoung', 'Lee, Sooyoung', 'Kuzume, Kazuyo', 'Koizumi, Munemitsu', 'Nishimura, Koji', 'Okamoto, Michiko', 'Kim, Seung-Hyun', 'Ye, Young Min', 'Hur, Gyu Young', 'Park, Hae-Sim', 'Kim, Sang-Heon', 'Jee, Young-Koo', 'Kim, Seung-Hyun', 'Choi, Hyunna', 'Ye, Young Min', 'Park, Hae-Sim', 'Van Khanh, Bui', 'Chu, Hieu Chi', 'Nguyet, Nguyen Nhu', 'Phuong, Nguyen Hoang', 'Roh, Joo Young', 'Kim, Hyun Jeong', 'Kim, Jung Eun', 'Lew, Bark-Lynn', 'Lee, Kyung Ho', 'Hong, Seung-Phil', 'Jang, Yong Hyun', 'Park, Kui Young', 'Seo, Seong Jun', 'Bae, Jung Min', 'Choi, Eung Ho', 'Suhr, Ki Beom', 'Lee, Seung Chul', 'Ko, Hyun-Chang', 'Park, Young Lip', 'Son, Sang Wook', 'Seo, Young Jun', 'Lee, Yang Won', 'Cho, Sang Hyun', 'Park, Chun Wook', 'Lee, Kun Hee', 'Kim, Sung Wan', 'Chu, Chia-Yu', 'Aw, Derrick', 'Ye, Young-Min', 'Bader, Giovanni', 'Dolfi, Fabrizio', 'Oliveira, Nathalie', 'Choi, Jae Chol', 'Jung, Jae Woo', 'Kang, Hye-Ryun', 'Kim, Kijeong', 'Choi, Byoung Whui', 'Shin, Jong Wook', 'Jung, Jae Woo', 'Choi, Jae Chol', 'Park, In Won', 'Choi, Byoung Whui', 'Kim, Jae Yeol', 'Lee, Jin-Young', 'Ha, Kyoung Won', 'Jeung, Yun-Jin', 'Yune, Sehyo', 'Lee, Byung-Jae', 'Choi, Dong-Chull', 'Oh, Mi-Jung', 'Lim, Young Hee', 'Lee, Eui Jun', 'Suh, Dongin', 'Suh, Dongin', 'Woo, Sung-Il', 'Woo, Sung-Il', 'Cho, Hwa Jin', 'Cho, Hwa Jin', 'Chung, Eun Hee', 'Chung, Eun Hee', 'Chung, Soo Youn', 'Shah, Ashok', 'Gera, Kamal', 'Ha, Kyoung Won', 'Oh, Mi-Jung', 'Lim, Young Hee', 'Yune, Sehyo', 'Paeng, Jae-Won', 'Jang, Mi-Jin', 'Lee, Byung-Jae', 'Choi, Dong-Chull', 'Lee, Jin-Young', 'Jang, Mi-Jin', 'Paeng, Jae-Won', 'Jeung, Yun-Jin', 'Lim, Young Hee', 'Oh, Mi-Jung', 'Ha, Kyoung Won', 'Lee, Byung-Jae', 'Choi, Dong-Chull', 'Yune, Sehyo', 'Lee, Jin-Young', 'Ito, Takahiro', 'Lee, Jin-Young', 'Yune, Sehyo', 'Lee, Byung-Jae', 'Choi, Dong-Chull', 'Jang, Mi-Jin', 'Paeng, Jae-Won', 'Kim, Young Eun', 'Kim, Young Nam', 'Lee, Yongseok', 'Kim, Jihye', 'Lee, Hwa Young', 'Lee, Sook Young', 'Kwon, Soon Seog', 'Kim, Young Kyoon', 'Rhee, Chin Kook', 'Kim, Sei Won', 'Lee, Hea Yon', 'Choi, Joon Young', 'Kim, In Kyoung', 'Aranzabal, Maria Ascension', 'Joral, Alejandro', 'Lizarza, Susana', 'Echenagusia, Miguel', 'Lasa, Eva Maria', 'Navarro, Jose Antonio', 'Jo, Eun-Jung', 'Jang, Sun-Mi', 'Song, Seung-Eon', 'Na, Hae-Jung', 'Kim, Chang-Hoon', 'Lee, Woo-Seop', 'Park, Hye-Kyung', 'Miyauchi, Sachiko', 'Uchida, Yoshitaka', 'Soma, Tomoyuki', 'Yamazaki, Susumu', 'Noguchi, Toru', 'Kobayashi, Takehito', 'Nakagome, Kazuyuki', 'Nagata, Makoto', 'Oh, Hea Lin', 'Kim, Do Kyun', 'Suh, Dongin', 'Koh, Young Yull', 'Lee, Jin-Young', 'Lee, Byung-Jae', 'Choi, Dong-Chull', 'Paeng, Jae-Won', 'Jang, Mi-Jin', 'Kim, Jihye', 'Kim, Young Nam', 'Yune, Sehyo', 'Kim, Sang-Hoon', 'Sohn, Jang Won', 'Yoon, Ho Joo', 'Shin, Dong Ho', 'Lee, Jae Hyung', 'Lee, Byoung Hoon', 'Kim, Youn-Seup', 'Park, Jae-Seuk', 'Jee, Young-Koo', 'Kim, Sang-Heon', 'Lee, Jin-Young', 'Paeng, Jae-Won', 'Jang, Mi-Jin', 'Choi, Dong-Chull', 'Lee, Byung-Jae', 'Lee, Yongseok', 'Kim, Young Eun', 'Yune, Sehyo', 'Yoon, Jisun', 'Zhang, Li', 'Cai, Xuxu', 'Feng, Yong', 'Yoon, Jong-Seo', 'Jeong, Kyunguk', 'Yoo, Hye-Soo', 'Lee, Sooyoung', 'Lee, Sooyoung', 'Lee, Hae-Jin', 'Lee, Noo Ri', 'Kim, Bo-Kyung', 'Jung, Minyoung', 'Kim, Dong Hye', 'Moniaga, Catharina S.', 'Kabashima, Kenji', 'Choi, Eung Ho', 'Yanagida, Noriyuki', 'Sato, Sakura', 'Sugizaki, Chizuko', 'Ebisawa, Motohiro', 'Kiehm, Jamie', 'Ponda, Punita', 'Farzan, Sherry', 'Weiss, Jared', 'Elera, Claudia', 'Destio, Catherine', 'Sison, Cristina', 'Lee, Annette', 'Ri, Soo Hyun', 'Lim, Chang Hoon', 'Pulido, Iñaki Izquierdo', 'Taubel, Jorg', 'Ferber, Georg', 'Masdeu, Eva Santamaria', 'Khayatzadeh, Alireza', 'Movahedi, Masoud', 'Ebisawa, Motohiro', 'Gharagozlou, Mohammad', 'Atasoy, Ulus', 'Techasintana, Patsharaporn', 'Gubin, Matt', 'Glascock, Jacqueline', 'Ridenhour, Suzanne', 'Magee, Joseph', 'Filho, Nelson Rosario', 'Neto, Herberto Jose Chong', 'Wandalsen, Gustavo Falbo', 'Dela Bianca, Ana Caroline', 'Aranda, Carolina', 'Sole, Dirceu', 'Mallol, Javier', 'Garcia-Marcos, Luis', 'Garcia-Marcos, Luis', 'Toh, Jennifer', 'Lee, Yoomie', 'Huang, Joyce', 'Jerschow, Elina', 'Shliozberg, Jenny', 'Satitsuksanoa, Pattraporn', 'Suratannon, Narissara', 'Wongpiyabovorn, Jongkonnee', 'Chatchatee, Pantipa', 'Ruxrungtham, Kiat', 'Jacquet, Alain', 'Yang, Min Suk', 'Lee, Jin Yong', 'Kim, Ja Yeun', 'Park, Han-Ki', 'Kim, Ju-Young', 'Song, Woo-Jung', 'Kang, Hye-Ryun', 'Park, Heung Woo', 'Chang, Yoon-Seok', 'Cho, Sang-Heon', 'Min, Kyung-up', 'Park, Chang-Han', 'Chang, Suk-Il', 'Song, Sook-Hee', 'Kim, Si-Heon', 'Choi, Gil-Soon', 'Kim, Su-Chin', 'Kim, Ji Hye', 'Ban, Ga Young', 'Shin, Yoo Seob', 'Park, Hae-Sim', 'Ye, Young Min', 'Hwang, Yoon Ha', 'Sim, Da Woon', 'Park, Kyung Hee', 'Park, Kyung Hee', 'Park, Hye Jung', 'Park, Hye Jung', 'Park, Jung-Won', 'Park, Jung-Won', 'Lee, Jae-Hyun', 'Lee, Jae-Hyun', 'Allen, Katrina', 'Beck, Cara', 'Koplin, Jennifer', 'Matheson, Melanie', 'Tang, Mimi', 'Ponsonby, Anne-Louise', 'Gurrin, Lyle', 'Dharmage, Shyamali', 'Wake, Melissa', 'Mcwilliam, Vicki', 'Liu, Xiaoying', 'Wang, Jing', 'Xiang, Li', 'Wang, Qun', 'Lee, Ji-Eun', 'Kim, Dong-Young', 'Rhee, Chae-Seo', 'Rhee, Chae-Seo', 'Vazquez-Nava, Francisco', 'Cho, Sang-Heon', 'Jeong, Jaewon', 'Perng, Diahn-Warng', 'Price, David', 'Neira, Glenn', 'Lin, Jiangtao', 'Semernik, Olga', 'Kim, Ha-Su', 'Jung, Jin-a', 'Jung, Ji-in', 'Miao, Qing', 'Xiang, Li', 'Cho, Sang-Heon', 'Jeong, Jaewon', 'Perng, Diahn-Warng', 'Lin, Jiangtao', 'Price, David', 'Neira, Glenn', 'Lee, Hyun Young', 'Park, Hae-Sim', 'Ye, Young Min', 'Kim, Su Chin', 'Farrokhi, Shokrollah', 'Gheiby, Mohammadkazem', 'Kim, Sang-Heon', 'Park, Heung Woo', 'Kim, Sang-Hoon', 'Jee, Young-Koo', 'Park, Sunjoo', 'Moon, Keun Ai', 'Kwon, Hyouk-Soo', 'Kim, Tae-Bum', 'Cho, You Sook', 'Moon, Hee-Bom', 'Lee, Kyoung Young', 'Hong, Gyong Hwa', 'Ha, Eun Hee', 'Han, Heejae', 'Park, Hye Jung', 'Park, Yoon Hee', 'Kim, Yoon-Jo', 'Lee, Kangtaek', 'Park, Jung-Won', 'Lee, Jae-Hyun', 'Slavyanskaya, Tatiana', 'Derkach, Vladislava', 'Park, Hye Jung', 'Hong, Chein-Soo', 'Lee, Jae-Hyun', 'Kim, Sungryeol', 'Park, Kyung Hee', 'Lee, Choong-Kun', 'Kang, Beodeul', 'Beom, Seung-Hoon', 'Shin, Sang Joon', 'Jung, Minku', 'Park, Jung-Won', 'Kim, Eun-Hee', 'Kim, Ji-Hye', 'Mo, Ji-Hun', 'Chung, Young-Jun', 'Kim, Mi-Ae', 'Park, Hae-Sim', 'Yoon, Moon Gyeong', 'Lee, Young-Soo', 'Kim, Ji Hye', 'Ban, Ga Young', 'Yoo, Hye-Soo', 'Shin, Yoo Seob', 'Ye, Young Min', 'Nahm, Dong-Ho', 'Miao, Qing', 'Xiang, Li', 'Li, Ying-Ji', 'Shimizu, Takako', 'Inagaki, Hirofumi', 'Hirata, Yukiyo', 'Takizawa, Hajime', 'Azuma, Arata', 'Yamamoto, Masayuki', 'Kawada, Tomoyuki', 'Kim, Min-Gu', 'Hong, Gyong Hwa', 'Lee, Kyoung Young', 'Ha, Eun Hee', 'Moon, Keun Ai', 'Park, Sunjoo', 'Kwon, Hyouk-Soo', 'Kim, Tae-Bum', 'Moon, Hee-Bom', 'Cho, You Sook', 'Kim, Jung-Hyun', 'Kim, Hyo-Jung', 'Park, So-Young', 'Seo, Bomi', 'Kim, Ji-Hye', 'Samivel, Ramachandran', 'Kim, Eun-Hee', 'Chung, Young-Jun', 'Mo, Ji-Hun', 'Soumya, M. S.', 'Inbaraj, G.', 'Chellaa, R.', 'Pawankar, Ruby', 'Choi, Wonsun', 'Park, Hae-Sim', 'Ye, Young Min', 'Kim, Ji Hye', 'Ban, Ga Young', 'Shin, Yoo-Seob', 'Braber, Saskia', 'Verheijden, Kim', 'Kraneveld, Aletta', 'Garssen, Johan', 'Folkerts, Gert', 'Willemsen, Linette', 'Eichhorn, Stephanie', 'Ferreira, Fatima', 'Pablos, Isabel', 'Kastner, Bianca', 'Schweidler, Bettina', 'Wildner, Sabrina', 'Briza, Peter', 'Park, Jung-Won', 'Arora, Naveen', 'Vieths, Stefan', 'Gadermaier, Gabriele', 'Park, Sung-Min', 'Lee, Won-Ku', 'Kim, Jeong-Min', 'Kim, Gun-Wook', 'Mun, Je-Ho', 'Kim, Hoon-Soo', 'Song, Margaret', 'Ko, Hyun-Chang', 'Kim, Moon-Bum', 'Kim, Byung Soo', 'Kim, Young Nam', 'Yune, Sehyo', 'Lee, Jin-Young', 'Kim, Jihye', 'Kim, Young Eun', 'Paeng, Jae-Won', 'Jang, Mi-Jin', 'Choi, Dong-Chull', 'Lee, Byung-Jae', 'Lee, Yongseok', 'Goh, Si Hui', 'Lee, Bee Wah', 'Soh, Jian Yi', 'Kang, Hyungoo', 'Kim, Hyunhee', 'Yum, Hye-Yung', 'Ye, Young Min', 'Park, Hae-Sim', 'Ban, Ga-Young', 'Kim, Ji Hye', 'Shin, Yoo Seob', 'Takizawa, Takumi', 'Tabata, Masahiko', 'Aizawa, Akira', 'Yagi, Hisako', 'Nishida, Yutaka', 'Arakawa, Hirokazu', 'Morikawa, Akihiro', 'Orosoo, Solongo', 'Braber, Saskia', 'Bol-Schoenmakers, Marianne', 'Akbari, Peyman', 'Jeurink, Prescilla V.', 'Jeurink, Prescilla V.', 'De Graaff, Priscilla', 'Smit, Joost J.', 'Van Esch, Betty C. A. M.', 'Garssen, Johan', 'Garssen, Johan', 'Fink-Gremmels, Johanna', 'Pieters, Raymond H. H.', 'Kim, Gun-Woo', 'Jo, Eun-Jung', 'Kim, Sujeong', 'Song, Woo-Jung', 'Chang, Yoon-Seok', 'Faruqi, Shoaib', 'Kim, Ju-Young', 'Kang, Mingyu', 'Kim, Min-Hye', 'Plevkova, Jana', 'Park, Heung Woo', 'Cho, Sang-Heon', 'Morice, Alyn', 'Lee, So-Hee', 'Kim, Sun-Sin', 'Lee, Seoung-Eun', 'Gemicioglu, Bilun', 'Misirligil, Zeynep', 'Cimrin, Arif Hikmet', 'Gunen, Hakan', 'Ozlu, Tevfik', 'Cilli, Aykut', 'Akyildiz, Levent', 'Bayram, Hasan', 'Uzaslan, Esra', 'Abadoglu, Oznur', 'Suerdem, Mecit', 'Kainuma, Keigo', 'Kim, Hyun-a', 'Kim, Ha-Su', 'Bae, Woo Yong', 'Jung, Jin-a', 'Kamenwa, Rose', 'Macharia, William', 'Said, Nusrat', 'Nerurkar, Vidya', 'Patel, Meenal', 'Bhatia, Simi', 'Choi, Inseon S.', 'Kim, Soo-Jeong', 'Won, Joo-Min', 'Park, Myeong-Soo', 'Nagao, Mizuho', 'Park, Dong Won', 'Sohn, Jang Won', 'Yhi, Ji Young', 'Moon, Ji-Yong', 'Kim, Sang-Heon', 'Kim, Tae Hyung', 'Shin, Dong Ho', 'Yoon, Ho Joo', 'Hyo, Yukiyoshi', 'Lee, Jaechun', 'Kim, Su Hee', 'Lee, Eunkyoung', 'Jung, Hahn Jin', 'Lim, Jaehyun', 'Hong, Seung-No', 'Han, Doo Hee', 'Rhee, Chae-Seo', 'Lee, Kun Song', 'Lee, Jaechun', 'Yang, Sun Young', 'Ahn, Mi Young', 'Lee, Jong Hoo', 'Golez, Jasmina', 'Tian, Hui-Qin', 'Cheng, Lei', 'Chen, Xin-Yuan', 'Moon, Ji-Yong', 'Kim, Sang-Heon', 'Kim, Tae Hyung', 'Yhi, Ji Young', 'Yoon, Ho Joo', 'Sohn, Jang Won', 'Shin, Dong Ho', 'Park, Dong Won', 'Cho, Won Im', 'Choi, Jong Sub', 'Suh, Dongin', 'Kang, Gyeong Hoon', 'Moon, Jin Soo', 'Ko, Jae Sung', 'Lee, Kyung Jae', 'Choi, Shin Jie', 'Luo, Wenting', 'Sun, Baoqing', 'Gao, Qi', 'Xiang, Li', 'Shen, Kunling', 'Jang, Yong Hyun', 'Bergmann, Karl-Christian', 'Sehlinger, Torsten', 'Bölke, Georg', 'Berger, Uwe', 'Zuberbier, Torsten', 'Kolodziejczyk, Joanna', 'Wojciechowska, Milena', 'Hnatyszyn-Dzikowska, Anna', 'Chojnacki, Micha', 'Bartuzi, Zbigniew', 'Masaki, Katsunori', 'Fukunaga, Koichi', 'Kamatani, Takashi', 'Ohtsuka, Kengo', 'Tanosaki, Takae', 'Matsusaka, Masako', 'Mochimaru, Takao', 'Kabata, Hiroki', 'Ueda, Soichiro', 'Suzuki, Yusuke', 'Kamei, Katsuhiko', 'Asano, Koichiro', 'Betsuyaku, Tomoko', 'Trafford, Karlee', 'Bulut, Ismet', 'Ozseker, Zeynep Ferhan', 'Horimukai, Kenta', 'Morita, Hideaki', 'Narita, Masami', 'Niizeki, Hironori', 'Matsumoto, Kenji', 'Ohya, Yukihiro', 'Saito, Hirohisa', 'Kabashima, Shigenori', 'Kondo, Mai', 'Inoue, Eisuke', 'Siebers, Robert', 'Wu, Francis F. S.', 'Siebers, Robert', 'Wu, Francis F. S.', 'Ting, Ming-Hui', 'Laio, Hung-En', 'Kuo, Tsung-Huai', 'Lee, Pei-Yuan', 'Maddox, Daniel Eugene', 'Ryu, Gwanghui', 'Kim, Hyo Yeol', 'Dhong, Hun-Jong', 'Hong, Sang Duk', 'Chung, Seung-Kyu', 'Higuchi, Osamu', 'Adachi, Yu-Ichi', 'Itazawa, Toshiko', 'Adachi, Yoko', 'Hamamichi, Miki', 'Nakabayashi, Motokazu', 'Ito, Yasunori', 'Wada, Takuya', 'Murakami, Gyoukei', 'Takao, Miki', 'Yamamoto, Junko', 'Jin, Hyun Jung', 'Yoon, Moon Gyeong', 'Ye, Young Min', 'Shin, Yoo-Seob', 'Kim, Seung-Hyun', 'Park, Hae-Sim', 'Min, Taek-Ki', 'Pyun, Bok-Yang', 'Lee, So-Yeon', 'Kim, Hyun Hee', 'Jang, Gwang-Cheon', 'Yu, Jinho', 'Suh, Dongin', 'Lee, Sooyoung', 'Park, Yong Mean', 'Kim, Jeong Hee', 'Yum, Hye-Yung', 'Kim, Kyung Won', 'Yang, Hyeon-Jong', 'Ahn, Kangmo', 'Kwon, Ji-Won', 'Sohn, Myung Hyun', 'Lee, Hae Ran', 'Kwon, Jung Hyun', 'Kim, Kyu-Earn', 'Hong, Soo-Jong', 'Cho, Su-Mi', 'Nahm, Dong-Ho', 'Kim, Myoung-Eun', 'Lee, Jin Hwa', 'Rhee, Chin Kook', 'Park, Hye Yun', 'Kim, Woo Jin', 'Park, Yong Bum', 'Yoo, Kwang-Ha', 'Kang, Heejeong', 'Yang, Hyeon-Jong', 'Min, Taek-Ki', 'Pyun, Bok-Yang', 'Suk, Lee Ju', 'Kim, Cheol Hong', 'Kwon, Jung Hyun', 'Lee, Sang Hyun', 'Seo, Wonhee', 'Kim, Kang-in', 'Park, Young Cheon', 'Yang, Hyeon-Jong', 'Min, Taek-Ki', 'Pyun, Bok-Yang', 'Kim, Sujeong', 'Jin, Sun', 'Lee, Jong-Myung', 'Jung, Hye-Jin', 'Park, Jung-Wha', 'Kim, Hyo-Jung', 'Kim, Tae-Bum', 'Cho, You Sook', 'Moon, Hee-Bom', 'Kwon, Hyouk-Soo', 'Park, So Young', 'Park, So-Young', 'Kim, Jung-Hyun', 'Seo, Bomi', 'Kim, Min-Gu', 'Kim, Youn Yee', 'Lee, Yena', 'Min, Taek-Ki', 'Yang, Hyeon-Jong', 'Pyun, Bok-Yang', 'Han, Suk Hee', 'Park, Suyeon', 'Lee, Jeongho', 'Hahn, Won-Ho', 'Jeon, Youhoon', 'Kim, Joo-Hee', 'Shin, Tae-Rim', 'Kim, Cheol-Hong', 'Hyun, In-Gyu', 'Choi, Jeong-Hee', 'Jang, Sun-Mi', 'Na, Hae-Jung', 'Song, Seung-Eon', 'Park, Hye-Kyung', 'Jo, Eun-Jung', 'Lee, Dong Hun', 'Lee, Jin-Young', 'Park, Yang', 'Oh, Jae-Won', 'Lee, Mi Hee', 'Hong, Soo-Jong', 'Hong, Soo-Jong', 'Lee, So-Yeon', 'Park, Joon Soo', 'Nahm, Dong-Ho', 'Yum, Hye-Yung', 'Yum, Hye-Yung', 'Choi, Kyu Young', 'Kim, Dong-Young', 'Palapinyo, Sirinoot', 'Klaewsongkram, Jettanong', 'Chen, Xing', 'Jin, Yuting', 'Hou, Xiaoming', 'Liu, Fengqin', 'Guo, Chunyan', 'Wang, Yulin', 'Okafuji, Ikuo', 'Tanaka, Yuya', 'Narabayashi, Shegeyuki', 'Tsuruta, Satoru', 'Jang, Yong Hyun', 'Ahn, Jun-Hong', 'Lee, Dong-Won', 'Chung, Jin Hong', 'Jin, Hyun Jung', 'Sohn, Min-Su', 'Park, Young a', 'Jeong, Kyunguk', 'Kim, Yoon Hee', 'Sol, In Suk', 'Yoon, Seo Hee', 'Kim, Kyung Won', 'Sohn, Myung Hyun', 'Kim, Kyu-Earn', 'Lee, Sooyoung', 'Kim, Ho', 'Kim, Ja Yeun', 'Lee, So-Yeon', 'Min, Taek-Ki', 'Song, Tae-Won', 'Ahn, Kangmo', 'Kim, Jihyun', 'Jang, Gwang-Cheon', 'Yang, Hyeon-Jong', 'Pyun, Bok-Yang', 'Kwon, Ji-Won', 'Sohn, Myung Hyun', 'Kim, Kyu-Earn', 'Yu, Jinho', 'Hong, Soo-Jong', 'Kwon, Jung-Hyun', 'Kim, Sung-Won', 'Lee, Sooyoung', 'Kim, Woo Kyung', 'Kim, Hyung Young', 'Kim, Hye-Young', 'Jeon, Youhoon', 'Lim, Chang Hoon', 'Jeong, Yeongsang', 'Kim, Su Jung', 'Chang, Hun Soo', 'Heo, Jeong-Seok', 'Bae, Da-Jeong', 'Lee, Jong-Uk', 'Kim, Ji-Na', 'Min, Chang-Gi', 'Song, Hyun Ji', 'Park, Jong-Sook', 'Kim, Soo Hyun', 'Park, Choon-Sik', 'Liu, Jing-Nan', 'Choi, Youngwoo', 'Shin, Yoo Seob', 'Park, Hae-Sim', 'Rezaei, Nima', 'Mahneh, Sedigheh Bahrami', 'Rezaei, Arezou', 'Sadr, Maryam', 'Movahedi, Masoud', 'Gang, Jun Seak', 'Park, Joon Soo', 'Kim, Seung Soo', 'Bang, Hyun Ho', 'Park, Kyeong Bae', 'Kim, Hye Sun', 'Kim, Tae Ho', 'Hwangbo, Young', 'Lee, Hyun Jung', 'Yoo, Gyeong Hee', 'Kim, Young Chang', 'Sato, Sakura', 'Yanagida, Noriyuki', 'Ebisawa, Motohiro', 'Palikhe, Sailesh', 'Park, Hae-Sim', 'Kim, Seung-Hyun', 'Kim, Ri-Yeon', 'Yang, Eun-Mi', 'Lee, Li Yuan Gabriella Nadine', 'Aw, Marion', 'Aw, Marion', 'Lee, Bee Wah', 'Lee, Bee Wah', 'Loo, Evelyn Xiu Ling', 'Chan, Yiong Huak', 'Shek, Lynette', 'Shek, Lynette', 'Kuo, I-Chun', 'Kuo, I-Chun', 'Quah, Phaik Ling', 'Quah, Phaik Ling', 'Llanora, Genevieve', 'Irvin, Gerez', 'Jung, Joo Hyun', 'Kang, Il Gyu', 'Kim, Seon Tae', 'Park, Hyoungmin', 'Kim, Seon Tae', 'Jung, Joo Hyun', 'Kang, Il Gyu', 'Park, Hyoungmin', 'Ko, Kwang-Pil', 'Lee, Jungsoo', 'Chu, Howard', 'Lee, Hemin', 'Shin, Jung U.', 'Park, Chang Ook', 'Lee, Kwang Hoon', 'Lee, Kwang Hoon', 'Kang, Hong Kyu', 'Lee, Dong Chang', 'Kim, Geun Jeon', 'Hwang, Jae Hyung', 'Ha, Jin Bu', 'Jeong, Su Hee', 'Kim, Ho', 'Hwang, Shinha', 'Lee, Whahee', 'Bazarsad, Enkhbayar', 'Narantsetseg, Logii', 'Sonomjamts, Munkhbayarlakh', 'Jang, Gwang-Cheon', 'Lee, Hyun-Hee', 'Lee, Chang-Jong', 'Lim, Huynsun', 'Soh, Ji-Eun', 'Song, Dae-Jin', 'Kwon, Ji-Won', 'Kim, Hyung Young', 'Seo, Ju-Hee', 'Kim, Byoung-Ju', 'Kim, Hyo-Bin', 'Lee, So-Yeon', 'Jang, Gwang-Cheon', 'Kim, Woo Kyung', 'Jung, Young-Ho', 'Hong, Soo-Jong', 'Shim, Jung Yeon', 'Bazarsad, Enkhbayar', 'Narantsetseg, Logii', 'Sonomjamts, Munkhbayarlakh', 'Pv, Prabhakarrao', 'Nadendla, Ranjitha', 'Fang, Juan', 'Zhao, Jing', 'Song, Dae-Jin', 'Seo, Sungchul', 'Yoo, Young', 'Kim, Yu-Ri', 'Choung, Ji Tae', 'Lee, Jee Hoo', 'Berings, Margot', 'De Ruyck, Natalie', 'Bachert, Claus', 'Gevaert, Philippe', 'Holtappels, Gabriële', 'Lee, Pureun-Haneul', 'Kim, Byeong-Gon', 'Park, Choon-Sik', 'Leikauf, George D.', 'Jang, An-Soo', 'Kimc, Byeong-Gon', 'Lee, Pureun-Haneul', 'Park, Choon-Sik', 'Jang, An-Soo', 'Park, Yang', 'Sohn, Min-Su', 'Jin, Hyun Jung', 'Lee, Dong-Won', 'Ahn, Jun-Hong', 'Chung, Jin Hong', 'Kim, Sae-in', 'Park, Han-Ki', 'Kim, Do-Yeon', 'Rho, Mina', 'Choi, Jun-Pyo', 'Kim, Yoon-Keun', 'Kamchaisatian, Wasu', 'Hiranras, Thitikul', 'Wongpun, Surinda', 'Chiraphorn, Phornthip', 'Tantachun, Anupan', 'Wongrassamee, Wannipa', 'Vatanasurkitt, Planee', 'Somboonkul, Naratip', 'Juthacharoenwong, Nattipat', 'Techapaitoon, Surangkana', 'Tuchinda, Montri', 'An, Sejin', 'Lee, Jae Ho', 'Shin, Ji-Hyeon', 'Kim, Soo Whan', 'Kim, Si Won', 'Kang, Jun Myung', 'Kim, Boo-Young', 'Kim, Byung-Guk', 'Kwon, Ji-Won', 'Kim, Woo Kyung', 'Kim, Hyung Young', 'Kim, Hyo-Bin', 'Seo, Ju-Hee', 'Lee, So-Yeon', 'Jang, Gwang-Cheon', 'Jung, Young-Ho', 'Hong, Soo-Jong', 'Kim, Byoung-Ju', 'Song, Dae-Jin', 'Shim, Jung Yeon', 'Lee, Jung-Won', 'Kim, Kyung Ho', 'Yoo, Young', 'Yoon, Won Suck', 'Seo, Sungchul', 'Kang, In Soon', 'Choi, Jae Won', 'Lim, Hye-Young', 'Choung, Ji Tae', 'Buela, Michelle', 'Nishimura, Koji', 'Park, Sang Chul', 'Chung, Hyo Jin', 'Kim, Chang-Hoon', 'Kang, Ju Wan', 'Hong, Seong-Chul', 'Lee, Keun-Hwa', 'Lee, Jaechun', 'Lee, Hye-Sook', 'Kim, Jeong Hong', 'Logii, Narantsetseg', 'Nyamdavaa, N.', 'Enkhbayar, B.', 'Oyuntsatsral, B.', 'Munkhbayarlakh, S.', 'Bazarsad, Enkhbayar', 'Sonomjamts, Munkhbayarlakh', 'Omarjee, Bashir', 'Li, Shuo', 'Hayashi, Miyuki', 'Pawankar, Ruby', 'Yamanishi, Shingo', 'Igarashi, Toru', 'Itoh, Yasuhiko', 'Gantulga, B.', 'Enkhbayar, B.', 'Munkhbayarlakh, S.', 'Narantsetseg, L.', 'Batsaikhan, Oyuntsatsral', 'Chen, Pei-Chi', 'Wang, Jiu-Yao', 'Leung, Nicki Y. H.', 'Wai, Christine Yee Yan', 'Leung, Patrick S. C.', 'Chu, Ka Hou', 'Doh, Eun Jin', 'Lee, Dong Hun', 'Choi, Mira', 'Yoon, Hyun-Sun', 'Kim, Kyu Han', 'Lim, Ji Soo', 'Baek, Ji Hyeon', 'Han, Man Yong', 'Lee, Seung Jin', 'Jeon, Youhoon', 'Lee, Kyung Suk', 'Jung, Young-Ho', 'Jee, Hye Mi', 'Shin, Youn Ho', 'Jiang, Yi', 'Liu, Miao', 'Naing, Chaw Su', 'Tan, Tze Chin', 'Chong, Yong Yeow', 'Kim, Young-Ho', 'Lee, Eun', 'Yang, Song-I', 'Cho, Hyun-Ju', 'Kim, Hyung Young', 'Kwon, Ji-Won', 'Jung, Young-Ho', 'Kim, Byoung-Ju', 'Seo, Ju-Hee', 'Kwon, Ho-Jang', 'Kim, Hyo-Bin', 'Lee, So-Yeon', 'Hong, Soo-Jong', 'Kim, Soo Hyun', 'Joseph, Jacqueline Elizabeth', 'Soumya, M. S.', 'Pawankar, Ruby', 'Kumar, Harshitha', 'Yang, Sohyoung', 'Woo, Sung-Il', 'Rezaei, Nima', 'Kose, Sukran', 'Serin, Basak Gol', 'Yalcin, Arzu Didem', 'Senger, Süheyla Serin', 'Erden, Mehmet', 'Serin, Ertan', 'Leung, Ting Fan', 'Leung, Agnes Sze-Yin', 'Kumar, Harshitha', 'Soumya, M. S.', 'Joseph, Jacqueline Elizabeth', 'Pawankar, Ruby', 'Chung, Eun Hee', 'Kim, Eunji', 'Yoo, Young', 'Yoo, Young', 'Choung, Ji Tae', 'Choung, Ji Tae', 'Seo, Sungchul', 'Seo, Sungchul', 'Kang, In Soon', 'Lee, Jue Seong', 'Hwang, Ji Hyen', 'Lee, Sang Min', 'Jung, Joo Hyun', 'Choi, Seung Joon', 'Joe, Eugene', 'Hwang, Hyunjung', 'Kang, Shin Myung', 'Kim, Yu Jin', 'Kyung, Sun Young', 'Park, Jeong-Woong', 'Jeong, Sung Hwan', 'Lee, Sang Pyo', 'Gaisina, Alina', 'Shilovskiy, Igor', 'Nikonova, Aleksandra', 'Kamyshnikov, Oleg', 'Khaitov, Musa', 'Mitin, Alexander', 'Viktoriya, Komogorova', 'Litvina, Marina', 'Sharova, Nina', 'Faiah, M. J.', 'Ismail, Intan H.', 'Miles, E. A.', 'Jamli, Faizah Mohamed', 'Choi, Jun-Pyo', 'Choi, Han-Byul', 'Kim, Yoon-Keun', 'Choi, Hyeon-Il', 'Yoon, Da-Il', 'Kang, Mingyu', 'Kim, Mi Yeoung', 'Kim, Sujeong', 'Jo, Eun-Jung', 'Lee, Seoung-Eun', 'Song, Woo-Jung', 'Lee, Sang Min', 'Park, Chansun', 'Chang, Yoon-Seok', 'Lee, Jaechun', 'Jee, Young-Koo', 'Choi, Inseon S.', 'Min, Kyung-up', 'Cho, Sang-Heon', 'Cho, Sang-Heon', 'Laskin, Anton', 'Kamyshnikov, Oleg', 'Babakhin, Alexander', 'Berzhets, Valentina', 'Khaitov, Musa', 'Lee, Jae Ho', 'An, Sejin', 'Chang, Yoon-Seok', 'Min, Kyung-up', 'Cho, Sang-Heon', 'Kim, Sae-Hoon', 'Kwon, Yong Eun', 'Jee, Young-Koo', 'Kim, Tae-Bum', 'Moon, Hee-Bom', 'Park, Hye-Kyung', 'Kang, Sung-Yoon', 'Choi, Jun-Pyo', 'Park, Han-Ki', 'Lee, Ji-Hyun', 'Kim, Yoon-Keun', 'Kim, Sang-Yoon', 'Hwang, Hyunjung', 'Joe, Eugene', 'Lee, Sang Min', 'Choi, Seung Joon', 'Jung, Joo Hyun', 'Seon, Yong Han', 'Kang, Shin Myung', 'Kim, Yu Jin', 'Kyung, Sun Young', 'Park, Jeong-Woong', 'Jeong, Sung Hwan', 'Lee, Sang Pyo', 'Khramykhoverchenko, Natalya', 'Sultana, Asma', None, 'Halwani, Rabih', 'Bahammam, Ahmed', 'Al Muhsen, Saleh', 'Kim, Sun Kyung', 'Nam, Kwang Il', 'Yang, Hyung Chae', 'Kim, Jeong-Eun', 'Lee, Ju Suk', 'Lee, Ji Hyun', 'Kang, Kyung Woo', 'Kim, Je-Kyung', 'Hahn, Youn-Soo', 'Jung, Jae-Yub', 'Baba, Yosuke', 'Yamazaki, Sususmu', 'Inage, Eisuke', 'Mori, Mari', 'Ohtsuka, Yoshikazu', 'Kantake, Masato', 'Shimizu, Toshiaki', 'Honjoh, Asuka', 'Yokokura, Tomoaki', 'Elhassan, Shaza Ali Mohammed', 'Beck, Caroline', 'Adeli, Mehdi', 'Baek, Heysung', 'Lee, Seung Jin', 'Baek, Ji Hyeon', 'Yoon, Jungwon', 'Choi, Sun Hee', 'Jung, Young-Ho', 'Shin, Youn Ho', 'Han, Man Yong', 'Na, Min Sun', 'Compalati, Enrico', 'Marogna, Maurizio', 'Huang, Huimin', 'Sun, Baoqing', 'Bai, Mingyu', 'Huo, Yiting', 'Zheng, Peiyan', 'Wei, Nili', 'Luo, Wenting', 'Andiappan, Anand', 'Minisini, Rosalba', 'Rötzschke, Olaf', 'Boggio, Elena', 'Gigliotti, Luca', 'Clemente, Nausicaa', 'Chiocchetti, Annalisa', 'Dianzani, Umberto', 'Pirisi, Mario', 'Villa, Elisa', 'Yamaide, Fumiya', 'Yonekura, Syuji', 'Shimojo, Naoki', 'Inoue, Yuzaburo', 'Okamoto, Yoshitaka', 'Setyoningrum, Retno Asih', 'Setiawati, Landia', 'Sumei, Sri', 'Iskandar, Deddy', 'Kompiyang, Indriyani Sang Ayu', 'Oguma, Tsuyoshi', 'Tanaka, Jun', 'Tomomatsu, Katsuyoshi', 'Asano, Koichiro', 'Uno, Keisuke', 'Matsuwaki, Yoshinori', 'Omura, Kazuhiro', 'Hayashi, Eika', 'Tatsumi, Norifumi', 'Kita, Hirohito', 'Otori, Nobuyoshi', 'Kojima, Hiromi', 'Khorasgani, Mohammadreza Fatemi', 'Lew, Dukhee/Betty', 'Lemessurier, Kim/S.', 'Moore, Joseph/a', 'Park, Jeoung-Eun', 'Yi, Ae-Kyung', 'Song, Chi/Young', 'Malik, Kafait/U', 'Kim, Ja Kyoung', 'Yang, Hyeon-Jong', 'Kim, Bong-Seong', 'Shin, Youn Ho', 'Lee, So-Yeon', 'Park, Geunhwa', 'Kim, Woo Kyung', 'Kim, Hyo-Bin', 'Baek, Heysung', 'Lim, Dae Hyun', 'Lim, Dae Hyun', 'Kim, Jin Tack', 'Suh, Dongin', 'Nano, Aimee Lou Manalo', 'Sun, Baoqing', 'Luo, Wenting', 'Nacaroglu, Hikmet Tekin', 'Erdem, Semiha Bahceci', 'Sumer, Ozlem', 'Karaman, Sait', 'Karkiner, Canan Sule Unsal', 'Asilsoy, Suna', 'Gunay, Ilker', 'Can, Demet', 'Kiers, Danielle', 'Wang, Jiu-Yao', 'Yin, Hsu Han', 'Kaplan, Allen', 'Joseph, Kusumam', 'Tholanikunnel, Baby G.', 'Dudek, Radim', 'Bilgin, Gulden', 'Surer, Hatice', 'Kilinc, Aytun Sadan', 'Yucel, Dogan', 'Lee, Ji Young', 'Kim, Jihyun', 'Yang, Hea-Kyoung', 'Kim, Minji', 'Lee, Sang-Il', 'Ahn, Kangmo', 'Moon, Sung Do', 'Kim, Byung-Keun', 'Cho, Sang-Heon', 'Min, Kyung-up', 'Chang, Yoon-Seok', 'Park, Heung Woo', 'Kang, Hye-Ryun', 'Song, Woo-Jung', 'Kang, Min-Koo', 'Kim, Ju-Young', 'Sohn, Kyonghee', 'Won, Ha Kyung', 'Lee, Seoung-Eun', 'Kim, Kyung-Mook', 'Bachert, Claus', 'Hsieh, Miao-Hsi', 'Wang, Jiu-Yao', 'Smith, Helen', 'Brown, Clare', 'Jones, Christina', 'Davies, Mark', 'Yoon, Won Suck', 'Lee, Hemin', 'Chu, Howard', 'Lee, Jungsoo', 'Shin, Jung U.', 'Park, Chang Ook', 'Lee, Kwang Hoon', 'Lee, Kwang Hoon', 'Kim, Seo Hyeong', 'Kim, Seo Hyeong', 'Noh, Ji Yeon', 'Kim, Ji Hye', 'Kim, Ji Hye', 'Yoon, Won Suck', 'L’huillier, Jean-Pierre', 'Autegarden, Jean-Eric', 'Bertrand, Catherine', 'Tardy, Dominique', 'Ismail, Intan Hakimah', 'Tang, Mimi', 'Licciardi, Paul', 'Oppedisano, Frances', 'Boyle, Robert', 'Robins-Browne, Roy', 'Yagi, Hisako', 'Koyama, Harumi', 'Nishida, Yutaka', 'Takizawa, Takumi', 'Arakawa, Hirokazu', 'Kang, Hong Kyu', 'Lee, Hemin', 'Lee, Jungsoo', 'Shin, Jung U.', 'Lee, Kwang Hoon', 'Lee, Kwang Hoon', 'Chu, Howard', 'Park, Chang Ook', 'Yoon, Na Young', 'Lee, Hyeyoung', 'Seo, Seong Jun', 'Choi, Eunhee', 'Wang, Hye-Young', 'Jung, Minyoung', 'Choi, Eung Ho', 'Kim, Dong Hye', 'Kim, Joo-Hee', 'Jang, Young-Sook', 'Choi, Jeong-Hee', 'Park, Sunghoon', 'Hwang, Young Il', 'Jang, Seung Hun', 'Jung, Ki-Suck', 'Kang, Mi-Jin', 'Suh, Dongin', 'Lee, Eun', 'Choi, Kil Yong', 'Jung, Young-Ho', 'Yang, Song-I', 'Kim, Bong-Soo', 'Kim, Ha-Jung', 'Koh, Juneyoung', 'Kim, Hyun-Jin', 'Ahn, Kangmo', 'Shin, Youn Ho', 'Cho, Hyun-Ju', 'Kim, Byoung-Ju', 'Kim, Young-Ho', 'Jung, Yean', 'Mamura, Mizuko', 'Yoon, Jeong-Hwan', 'Nakae, Susumu', 'Lee, Inkyu', 'Matsumoto, Isao', 'Sumida, Takayuki', 'Han, Jin Soo', 'Sudo, Katsuko', 'Ju, Ji Hyeon', 'Yap, Gaik Chin', 'Liu, Wen Tso', 'Oh, Seungdae', 'Hong, Pei Ying', 'Huang, Chiung Hui', 'Aw, Marion', 'Shek, Lynette', 'Lee, Bee Wah', 'Byun, Young Seok', 'Kim, Sung Wan', 'Koh, Tae Kyung', 'Jo, Joong-Saeng', 'Lee, Kun Hee', 'Kwon, Chul', 'Dong, Sung-Hwa', 'Kim, Myung Shin', 'Park, Chansun', 'Cho, Han Seok', 'Kim, Min-Ju', 'Kim, Min Ji', 'Park, Young Ok', 'Lee, Hye Yeong', 'Kim, Hee Seong', 'Lee, Eun', 'Cho, Hyun-Ju', 'Yu, Jinho', 'Hong, Soo-Jong', 'Hwang, Keum Hee', 'Kim, Jung-Hyun', 'Cho, You Sook', 'Kim, Sae-Hoon', 'Kwon, Hyouk-Soo', 'Yoo, Mira', 'Kim, Hyo-Jung', 'Park, So-Young', 'Shin, Bomi', 'Park, So Young', 'Seo, Bomi', 'Kim, Min-Gu', 'Moon, Hee-Bom', 'Park, Jin-Ah', 'Kim, Tae-Bum', 'Lee, Jaemoon', 'Jeong, Jin Hyeok', 'Kang, Tae Wook', 'Yoo, Han Seok', 'Cho, Yong Hee', 'Cho, Seok Hyun', 'Kim, Kyung Rae', 'Lee, Jue Seong', 'Kee, Sun-Ho', 'Kim, Sewon', 'Yoo, Young', 'Na, Heung Sik', 'Back, Seung Keun', 'Lee, Seung Jin', 'Seo, Bo Seon', 'Baek, Ji Hyeon', 'Lee, Kyung Suk', 'Jung, Young-Ho', 'Jee, Hye Mi', 'Shin, Youn Ho', 'Han, Man Yong', 'Kim, Mi-Ae', 'Nam, Young-Hee', 'Jeon, Dong Sub', 'Lee, Soo-Keol', 'Park, Jisun', 'Moon, Seung Hyun', 'Lin, Rong Jun', 'Guan, Ren Zheng', 'Park, Gyeong Yul', 'Yoon, Hyun-Sun', 'Choi, Woo-Hyeok', 'Baek, Heysung', 'Park, Jin-Sung', 'Kwon, Eunmi', 'Callaway, Zac', 'Kim, Chang-Keun', 'Fujisawa, Takao', 'Zhang, Qingling', 'Qiu, Rihuang', 'Li, Naijian', 'Yang, Zhaowei', 'Li, Jing', 'Chung, Kian Fan', 'Zhong, Nanshan', 'Hon, Kam Lun E.', 'Tsang, Yin Ching K.', 'Leung, Ting Fan', 'Jang, Yoon Young', 'Chung, Hai Lee', 'Lee, Seung Gook', 'Na, Ji Hyun', 'Lee, Jong Hoon', 'Nam, Young-Hee', 'Jeon, Dong Sub', 'Lee, Soo-Keol', 'Yamamoto, Mikita', 'Sato, Sakura', 'Yanagida, Noriyuki', 'Ogawa, Ayako', 'Ogura, Kanako', 'Takahashi, Kyohei', 'Nagakura, Kenichi', 'Emura, Shigehito', 'Asaumi, Tomoyuki', 'Iikura, Katsuhito', 'Ebisawa, Motohiro', 'Okada, Yu', 'Luo, Jiaying', 'Lan, Xiao', 'Sun, Baoqing', 'Chen, Zhao', 'Sun, Guiyuan', 'Li, Shimin', 'Hu, Jiaqing', 'Choi, Woo-Hyeok', 'Baek, Heysung', 'Nam, Young-Hee', 'Jeon, Dong Sub', 'Nam, Hee-Joo', 'Noh, Yeo Myeong', 'Kim, Sang Hee Kim', 'Park, Ye Suel', 'Lee, Soo-Keol', 'Choi, Yean Jung', 'Lee, Si Hyeon', 'Kim, Young-Ho', 'Kang, Mi-Jin', 'Cho, Hyun-Ju', 'Lee, Eun', 'Yang, Song-I', 'Shin, Youn Ho', 'Ahn, Kangmo', 'Kim, Kyung Won', 'Kim, Yoon Hee', 'Lee, So-Yeon', 'Chang, Hyoung Yoon', 'Choi, In Ae', 'Lee, Kyung-Sook', 'Shin, Yee-Jin', 'Kim, Yoon Hee', 'Kim, Min Jung', 'Sol, In Suk', 'Yoon, Seo Hee', 'a Park, Young', 'Kim, Kyung Won', 'Sohn, Myung Hyun', 'Kim, Kyu-Earn', 'Lee, Yong Ju', 'Sol, In Suk', 'Kim, Kyu-Earn', 'Kim, Yoon Hee', 'Kim, Min Jung', 'Yoon, Seo Hee', 'Lee, Yong Ju', 'Kim, Kyung Won', 'a Park, Young', 'Sohn, Myung Hyun', 'Park, Sung Joo', 'Kwon, Ji-Won', 'Kim, Woo Kyung', 'Kim, Hyung Young', 'Kim, Hyo-Bin', 'Seo, Ju-Hee', 'Lee, So-Yeon', 'Jang, Gwang-Cheon', 'Jung, Young-Ho', 'Hong, Soo-Jong', 'Kim, Byoung-Ju', 'Song, Dae-Jin', 'Yang, Yun Seok', 'Shim, Jung Yeon', 'Jang, Yoon Young', 'Chung, Hai Lee', 'Kim, Ji Hye', 'Lee, Hyun Seok', 'Lee, Chang Ho', 'Cho, Changbum', 'Lim, Yun-Kyu', 'Kim, Kyu Rang', 'Kim, Mijin', 'Kim, Baek-Jo', 'Kim, Young-Min', 'Han, Youngshin', 'Kim, Jihyun', 'Cheong, Hae-Kwan', 'Jeon, Byoung-Hak', 'Ahn, Kangmo', 'Ming, Chuang/Yao', 'Wang, Jiu-Yao', 'Ling, Ye/Yi', 'Huang, Huimin', 'Sun, Baoqing', 'Chen, Yun', 'Zheng, Peiyan', 'Wei, Nili', 'Luo, Wenting', 'Lee, Do Hyeong', 'Choi, Gil-Soon', 'Kim, Hee-Kyoo', 'Park, Han Su', 'Park, So-Young', 'Kim, Hyo-Jung', 'Seo, Bomi', 'Kim, Jung-Hyun', 'Kim, Min-Gu', 'Kwon, Hyouk-Soo', 'Cho, You Sook', 'Moon, Hee-Bom', 'Kim, Tae-Bum', 'Lee, Yoon Su', 'Shin, Eun-Soon', 'Tanaka, Akio', 'Morioke, Satoshi', 'Ohya, Yukihiro', 'Shimojo, Naoki', 'Akasawa, Akira', 'Hide, Michihiro', 'Shizukawa, Hiroko', 'Watanabe, Naoto', 'Shin, Meeyong', 'Jang, Myeong Sun', 'Nam, Young-Hee', 'Noh, Yeo Myeong', 'Jeon, Dong Sub', 'Nam, Hee-Joo', 'Kim, Sang Hee Kim', 'Park, Ye Suel', 'Lee, Soo-Keol', 'Jung, Ji-in', 'Kim, Ha-Su', 'Kim, Hyun-a', 'Jung, Jin-a', 'Goh, Anne', 'Rao, Rajeshwar', 'Nandanan, Bindu', 'Van Elburg, Ruurd', 'Chien, Chua Mei', 'Jo, Juandy', 'Garssen, Johan', 'Garssen, Johan', 'Knippels, Leon', 'Sandalova, Elena', 'Chiang, Wen Chin', 'Nam, Young-Hee', 'Juong, Ji Young', 'Kim, Soo Jin', 'Kim, Eun Young', 'Lee, Su Mi', 'Son, Young Ki', 'Nam, Hee-Joo', 'Kim, Ki-Ho', 'Lee, Soo-Keol', 'Park, Da-Eun', 'Kang, Hye-Ryun', 'Park, Heung Woo', 'Lee, Hyun Seung', 'Chang, Yoon-Seok', 'Park, Jung-Won', 'Cho, Sang-Heon', 'Min, Kyung-up', 'Song, Woo-Jung', 'Lim, Hyunwook', 'Seo, Sungchul', 'Choung, Ji Tae', 'Yoo, Young', 'Park, Jun-Sik', 'Kim, Byung Kwan', 'Won, Ha Kyeong', 'Kang, Hye-Ryun', 'Kim, Byung-Keun', 'Moon, Sung Do', 'Kim, Ju-Young', 'Lee, So-Hee', 'Song, Woo-Jung', 'Park, Heung Woo', 'Kang, Min-Koo', 'Kim, Sun-Sin', 'Cho, Sang-Heon', 'Min, Kyung-up', 'Chang, Yoon-Seok', 'Sohn, Kyoung Hee', 'Kim, Kyung-Mook', 'Kim, Ki-Woong', 'Jang, Hak Chul', 'Nam, Young-Hee', 'Jeon, Dong Sub', 'Nam, Hee-Joo', 'Noh, Yeo Myeong', 'Kim, Sang Hee Kim', 'Park, Ye Suel', 'Lee, Soo-Keol', 'Leung, Ting Fan', 'Tang, Man Fung', 'Sy, Hing Yee', 'Chan, Wa Cheong', 'Tam, Wilson Wai San', 'Chung, Seung Kyu', 'Kim, Sujin', 'Hong, Sang Duk', 'Kim, Hyo Yeol Kim Hyo Yeol', 'Dhong, Hun-Jong', 'Jeong, Jong in', 'Nam, Young-Hee', 'Jeon, Dong Sub', 'Lee, Soo-Keol', 'Lee, Ji Won', 'Kang, Mingyu', 'Kim, Soon-Hee', 'Bae, Boram', 'Kim, Sujeong', 'Kang, Hye-Ryun', 'Chang, Yoon-Seok', 'Song, Woo-Jung', 'Park, Da-Eun', 'Lee, Hyun Seung', 'Park, Heung Woo', 'Park, Han-Ki', 'Park, Jung-Won', 'Nam, Young-Hee', 'Jeon, Dong Sub', 'Nam, Hee-Joo', 'Noh, Yeo Myeong', 'Kim, Sang Hee Kim', 'Park, Ye Suel', 'Lee, Soo-Keol', 'Hou, Yung-I', 'Wang, Jiu-Yao', 'Kim, Ja Hyeong', 'Hee, Seol Jae', 'Ha, Eun-Hee', 'Park, Hyesook', 'Ha, Mina', 'Hong, Yun-Chul', 'Kim, Yangho', 'Chang, Namsoo', 'Soma, Yuta', 'Watanabe, So', 'Pawankar, Ruby', 'Suzaki, Harumi', 'Kobayashi, Hitome', 'Nam, Young-Hee', 'Park, Chansun', 'Lee, Soo-Keol', 'Lee, Jongrok', 'Roh, Jooyoung', 'Ryu, Haryeong', 'Kim, Cheol-Woo', 'Cho, Jae Hwa', 'Eom, Mi Ra', 'Kang, Ji Young', 'Lee, Hye Gyeung', 'Choi, Hae Young', 'Lee, Hye Jin', 'Woo, Ju Yun', 'Byun, Ji Yeon', 'Choi, You Won', 'Kim, Ja Hyeong', 'Ha, Eun-Hee', 'Park, Hyesook', 'Ha, Mina', 'Hong, Yun-Chul', 'Kim, Yangho', 'Chang, Namsoo', 'Kwon, Jae-Woo', 'Chang, Hun Soo', 'Heo, Jeong-Seok', 'Lee, Jong-Uk', 'Park, Jong-Sook', 'Kim, Eusom', 'Kim, Soo Hyun', 'Park, Choon-Sik', 'Choi, Hae Young', 'Byun, Ji Yeon', 'Woo, Ju Yun', 'Choi, You Won', 'Jin, Hyun-Ju', 'Son, Jin-Hwa', 'Kim, Jeong-Min', 'Kim, Gun-Wook', 'Mun, Je-Ho', 'Song, Margaret', 'Ko, Hyun-Chang', 'Kim, Moon-Bum', 'Kim, Hoon-Soo', 'Kim, Byung Soo', 'Van Nunen, Sheryl', 'Van Nguyen, Dinh', 'Elias, Anthony', 'Lauer, Susannah Olivia', 'Lee, Seung-Chul', 'Lee, Ho-June', 'Bae, Jung Min', 'Ono, Emi', 'Dong, Sung-Hwa', 'Koh, Tae Kyung', 'Byun, Young Seok', 'Kim, Sung Wan', 'Jo, Joong-Saeng', 'Kwon, Chul', 'Lee, Kun Hee', 'Liu, Li-Fan', 'Lee, Sunghee', 'Chen, Wei-Leng', 'Wang, Jiu-Yao', 'Bae, Youin', 'Park, Gyeong-Hun', 'Kim, Suk Yeon', 'Lee, Hyun Seung', 'Song, Woo-Jung', 'Kang, Mingyu', 'Park, Han-Ki', 'Park, Da-Eun', 'Kang, Hye-Ryun', 'Park, Heung Woo', 'Chang, Yoon-Seok', 'Kim, Hye-Young', 'Min, Kyung-up', 'Cho, Sang-Heon', 'Lee, Ji-Won', 'Bae, Boram', 'Park, Jung-Won', 'Suzuki, Yasuhiro', 'Bulut, Ismet', 'Ozseker, Zeynep Ferhan', 'Ismail, Intan Hakimah', 'Boyle, Robert', 'Licciardi, Paul', 'Oppedisano, Frances', 'Robins-Browne, Roy', 'Tang, Mimi', 'Lee, Ji Won', 'Lee, Hyun Seung', 'Kang, Mingyu', 'Park, Da-Eun', 'Park, Han-Ki', 'Kim, Soon-Hee', 'Song, Woo-Jung', 'Kang, Hye-Ryun', 'Park, Heung Woo', 'Chang, Yoon-Seok', 'Park, Chang-Han', 'Chang, Suk-Il', 'Song, Sook-Hee', 'Min, Kyung-up', 'Cho, Sang-Heon', 'Bae, Boram', 'Shieh, Grace', 'Kim, Min Jung', 'Hong, Jung Yeon', 'Yoon, Seo Hee', 'Shim, Doo Hee', 'Sol, In Suk', 'Kim, Yoon Hee', 'Kim, Mi Na', 'Lee, Kyung Eun', 'Kim, Kyung Won', 'Sohn, Myung Hyun', 'Kim, Kyu-Earn', 'Lee, Jae Myun', 'Chng, Hiok Hee', 'Kim, Dong Chan', 'Yang, Song-I', 'Lee, Hae Ran', 'Seo, An Deok', 'Lee, So Yeon', 'Artesani, Maria Cristina', 'Francalanci, Paola', 'Dahdah, Lamia', 'Schreiner, Thomas', 'Fiocchi, Alessandro', 'Chakraborty, Kaushik', 'Won, Ha Kyeong', 'Kim, Ju-Young', 'Jo, Eun-Jung', 'Sohn, Kyoung Hee', 'Kim, Kyung-Mook', 'Park, Heung Woo', 'Chang, Yoon-Seok', 'Cho, Sang-Heon', 'Song, Woo-Jung', 'Kim, Byung-Keun', 'Yonekura, Syuji', 'Okamoto, Yoshitaka', 'Hur, Gyu Young', 'Ye, Young Min', 'Kim, Joo-Hee', 'Jung, Ki-Suck', 'Kim, Junga', 'Shim, Jae Jeong', 'Park, Hae-Sim', 'Sekimoto, Kazuhiro', 'Sugai, Kazuko', 'Tsuchimoto, Keiji', 'Uehara, Hiromi', 'Ikeda, Masanori', 'Chung, Euncho', 'Park, Kang Seo', 'Choi, Yean Jung', 'Park, Jeewon', 'Hong, Soo-Jong', 'Lee, So Yeon', 'Jacquet, Alain', 'Buaklin, Arun', 'Malainual, Nat', 'Roopashree, S.', 'Kim, Kyu Rang', 'Kim, Mijin', 'Cho, Changbum', 'Kim, Baek-Jo', 'Oh, Jae-Won', 'Han, Mae Ja', 'Cho, Hyun-Ju', 'Shin, Youn Ho', 'Lee, Eun', 'Kim, Young-Ho', 'Lee, Darae', 'Kang, Mi-Jin', 'Yang, Song-I', 'Ahn, Kangmo', 'Kim, Kyung Won', 'Kim, Yoon Hee', 'Won, Hye-Sung', 'Kim, Soo Hyun', 'Choi, Suk-Joo', 'Kim, Young Han', 'Jun, Jong Kwan', 'Kim, Eun-Jin', 'Lee, Jeom Gyu', 'Lee, So-Yeon', 'Hong, Soo-Jong', 'Suh, Dongin', 'Amagai, Yosuke', 'Tanaka, Akane', 'Matsuda, Hiroshi', 'Mösges, Ralph', 'Dieterich, Pauline', 'Astvatsatourov, Anatoli', 'Hüser, Christoph', 'Singh, Jaswinder', 'Shah-Hosseini, Kija', 'Allekotte, Silke', 'Compalati, Enrico', 'Sohn, Kyoung Hee', 'Song, Woo-Jung', 'Kim, Byung-Keun', 'Kim, Ju-Young', 'Yang, Min Suk', 'Lee, So-Hee', 'Kim, Sae-Hoon', 'Kang, Hye-Ryun', 'Park, Heung Woo', 'Kim, Sun-Sin', 'Min, Kyung-up', 'Cho, Sang-Heon', 'Chang, Yoon-Seok', 'Chang, Woo-Sung', 'Do, Ji-Hye', 'Kim, Yeon-Seop', 'Yoon, Dankyu', 'Lim, Hye-Sun', 'Lee, Jeom-Kyu', 'Kim, Eun-Jin', 'Thong, Bernard', 'Cheng, Yew Kuang', 'Hou, Jinfeng', 'Leong, Khai Pang', 'Tan, Justina', 'Chia, Faith', 'Chan, Grace', 'Tan, Sze-Chin', 'Tan, Teck Choon', 'Tang, Chwee Ying', 'Chng, Hiok Hee', 'Park, Chan-Sun', 'Kim, Mi Yeoung', 'Kim, Eun-Young', 'Shin, Jae-Gook', 'Choi, Jae-Hyeog', 'Park, Saegwang', 'Kim, Yeonye', 'Lim, Kyung-Hwan', 'Jung, Jae Woo', 'Kang, Mingyu', 'Kim, Ju-Young', 'Kim, Ju-Young', 'Kim, Hyun Jeong', 'Woo, Yeon-Ju', 'Jung, Soo-Youn', 'Kang, Hye-Ryun', 'Kang, Hye-Ryun', 'Porée, Thierry', 'Boukhettala, Nabile', 'Furon, Emeline', 'Bullimore, Alan David', 'Heath, Matthew', 'Hewings, Simon', 'Skinner, Murray', 'Kurowski, Marcin', 'Krysztofiak, Hubert', 'Wardzynska, Aleksandra', 'Jarzebska, Marzanna', 'Jurczyk, Janusz', 'Kowalski, Marek L.', 'Kim, So Ri', 'Lee, Yong Chul', 'Kim, Dong Im', 'Rhee, Yang Keun', 'Lee, Heung Bum', 'Park, Seoung Ju', 'Choe, Yeong Hun Choe', 'Park, Seung Yong', 'Kim, Joo-Hee', 'Park, Sunghoon', 'Hwang, Young Il', 'Jang, Seung Hun', 'Jung, Ki-Suck', 'Min, Jiang', 'Guang-Min, Nong', 'Nag, Nalin', 'Indawati, Wahyuni', 'Bullimore, Alan David', 'Heath, Matthew', 'Skinner, Murray', 'Seo, Seong Jun', 'Oh, Won Jong', 'Bullimore, Alan David', 'Skinner, Murray', 'Heath, Matthew', 'Bell, Andrew', 'Hasanzadeh, Hournaz', 'Sadeghzade, Salman', 'Rezaei, Nima', 'Zarebidoki, Alireza', 'Cho, Kyu-Sup', 'Oh, Moo-Young', 'Kim, Sung-Woo', 'Koizumi, Munemitsu', 'Kuzume, Kazuyo', 'Park, Kui Young', 'Oh, Won Jong', 'Babaie, Delara', 'Nabavi, Mohammad', 'Zandieh, Fariborz', 'Moini, Mehrdad Amir', 'Chavoshzadeh, Zahra', 'Seifi, Hamideh', 'Sahragard, Mitra', 'Mesdaghi, Mehrnaz', 'Bemanian, Mohammad Hassan', 'Choi, Sun Young', 'No, Yeon a', 'Kiedik, Dorota', 'Muszynska, Agnieszka', 'Pirogowicz, Iwona', 'Fal, Andrzej M.', 'Motomura, Chikako', 'Wakatsuki, Masatoshi', 'Akamine, Yuko', 'Iwata, Mihoko', 'Matsuzaki, Hiroshi', 'Taba, Naohiko', 'Murakami, Yoko', 'Odajima, Hiroshi', 'Ghrahani, Reni', 'Takaoka, Yuri', 'Lee, Jong-Uk', 'Heo, Jeong-Seok', 'Bae, Da-Jeong', 'Song, Hyun Ji', 'Park, Choon-Sik', 'Park, Jong-Sook', 'Cho, Jae Hoon', 'Choi, Ji Ho', 'Febriana, Fiska', 'Ghrahani, Reni', 'Sapartini, Gartika', 'Setiabudiawan, Budi', 'Nam, Young-Hee', 'Kim, Mi Yeoung', 'Choi, Gil-Soon', 'Park, Chan-Sun', 'Huang, Chiung-Hui', 'Soh, Jian Yi', 'Shek, Lynette', 'Shek, Lynette', 'Delsing, Dianne J.', 'Lee, Bee Wah', 'Lee, Bee Wah', 'Goh, Si Hui', 'Chiang, Wen Chin', 'Loh, Wenyin', 'Yang, Hea-Kyoung', 'Lee, Ji Young', 'Kim, Minji', 'Ahn, Kangmo', 'Kim, Jihyun', 'Kim, Young-Min', 'Kim, Hye-Young', 'Park, Yong Mean', 'Kim, Woo Kyung', 'Lee, So-Yeon', 'Jeong, Jongin', 'Hong, Sang Duk', 'Chung, Seung Kyu', 'Dhong, Hun-Jong', 'Kim, Hyo Yeol', 'Kim, Sujin', 'Bak, Hana', 'Son, Hye-Rim', 'Lee, Si-Eun', 'Kim, Kwang-Jin', 'Lim, Young-Wook', 'Kim, Ho-Hyun', 'Lee, Yong-Won', 'Han, Man Yong', 'Jung, Young-Ho', 'Jee, Hye Mi', 'Lee, Seung Jin', 'Lee, Kyung Suk', 'Kim, Mi-Ae', 'Lee, Jaechun', 'Lee, Eunkyoung', 'Golez, Jasmina', 'Bae, Da-Jeong', 'Min, Chang-Gi', 'Lee, Jong-Uk', 'Park, Jong-Sook', 'Chang, Hun Soo', 'Park, Choon-Sik', 'Jang, An-Soo', 'Kim, Ha-Jung', 'Kim, Young-Joon', 'Jung, Bok Kyoung', 'Lee, Seung-Hwa', 'Kang, Mi-Jin', 'Jeong, Sekyoo', 'Lee, Eun', 'Cho, Hyun-Ju', 'Kim, Young-Ho', 'Yang, Song-I', 'Kim, Seo Hee', 'Hong, Soo-Jong', 'Halwani, Rabih', 'Al Muhsen, Saleh', 'Sultana, Asma', 'Al-Faraj, Achraf', 'Kanana, Rosan', 'Afzal, Sibtain', 'Al Kufaidi, Roaa', 'Kim, Hee-Kyoo', 'Oak, Chul-Ho', 'Choi, Gil-Soon', 'Moon, Ye-Jin', 'Park, Eun-Kee', 'Abrari, Mina', 'Amirzargar, Ali Akbar', 'Zarebidoki, Alireza', 'Ha, Mina', 'Hong, Soo-Jong', 'Seo, Ju-Hee', 'Kang, Mingyu', 'Cho, Byung-Ha', 'Park, Han-Ki', 'Park, Han-Ki', 'Kim, Kyung-Mook', 'Park, Chang-Han', 'Park, Heung Woo', 'Park, Heung Woo', 'Chang, Yoon-Seok', 'Chang, Yoon-Seok', 'Chang, Yoon-Seok', 'Song, Sook-Hee', 'Kim, Mi-Kyeong', 'Kim, Mi-Kyeong', 'Cho, Sang-Heon', 'Chang, Suk-Il', 'Min, Kyung-up', 'Min, Kyung-up', 'Morice, Alyn', 'Choi, Jungi', 'Han, Yusok', 'Park, Jin-Sung', 'Kwon, Eunmi', 'Kim, Chang-Keun', 'Sapartini, Gartika', 'Kim, Ji-Na', 'Shin, Seungwoo', 'Chang, Hun Soo', 'Shim, Eun-Young', 'Jun, Ji Ah', 'Lee, Hyeonju', 'Park, Jong-Sook', 'Park, Choon-Sik', 'Sepiashvili, Revaz', 'Khachapuridze, Darejan', 'Gamkrelidze, Sofio', 'Chikhladze, Manana', 'Lee, Seung-Eun', 'Kim, Yun-Seong', 'Jeon, Doo-Soo', 'Cho, Woo-Hyun', 'Yeo, Hye-Ju', 'Yoon, Seong-Hoon', 'Kim, Seung-Hyun', 'Lee, Taehyeong', 'Song, Hyun Ji', 'Park, Choon-Sik', 'Jun, Ji Ah', 'Park, Jong-Sook', 'Yoon, Dankyu', 'Kim, Yeon-Seop', 'Chang, Woo-Sung', 'Kang, Mi-Jin', 'Hong, Soo-Jong', 'Lee, Jeom-Kyu', 'Kim, Eun-Jin', 'Park, Minkee', 'Lee, Nanju Alice', 'Rost, Johanna', 'Muralidharan, Sridevi', 'Campbell, Dianne', 'Mehr, Sam', 'Lee, Seung-Hwa', 'Yoon, Seon-Joo', 'Kim, Ha-Jung', 'Lee, Eun', 'Yang, Song-I', 'Jung, Young-Ho', 'Yu, Ho-Sung', 'Kim, Hee-Suk', 'Park, Yeon Hee', 'Lee, So-Yeon', 'Park, Jun-Sung', 'Jun, Hyun Ok', 'Won, Ha Kyeong', 'Kang, Min-Koo', 'Moon, Sung Do', 'Kim, Byung-Keun', 'Kim, Ju-Young', 'Cho, Sang-Heon', 'Kang, Hye-Ryun', 'Shim, Ji-Su', 'Chung, Soo Jie', 'Choi, Jaehee', 'Ahn, Kangmo', 'Kim, Kwanghoon', 'Kim, Jihyun', 'Lee, Jiyoung', 'Park, Bo Bae', 'Nho, In Young', 'Park, Chang-Han', 'Kim, Jang Min', 'Chang, Suk-Il', 'Kim, Sun Kyung', 'Yang, Hyung Chae', 'Nam, Kwang Il', 'Lee, Jeongmin', 'Lee, Sooyoung', 'Jeong, Kyunguk', 'Jeon, Se-Ah', 'Fujiwara, Midori', 'Shindo, Shoko', 'Murota, Hiroyuki', 'Tahara, Mayuko', 'Takahashi, Aya', 'Katayama, Ichiro', 'Jung, Jae Woo', 'Song, Hyun Ji', 'Lee, Taehyeong', 'Jang, An-Soo', 'Park, Jong-Sook', 'Chang, Hun Soo', 'Park, Choon-Sik', 'Choi, Byoung Whui', 'Kim, Min-Hye', 'Bae, Da-Jeong', 'Song, Hyun Ji', 'Lee, Taehyeong', 'Jun, Ji Ah', 'Park, Jong-Sook', 'Jang, An-Soo', 'Chang, Hun Soo', 'Cho, Young Joo', 'Park, Choon-Sik', 'Mun, Sue Jean', 'Kuroda, Etsushi', 'Ozasa, Koji', 'Ishii, Ken', 'Kim, Sunmi', 'Park, Gyeong-Hun', 'Song, Hyun Ji', 'Lee, Taehyeong', 'Jun, Ji Ah', 'Chang, Hun Soo', 'Park, Jong-Sook', 'Park, Choon-Sik', 'Kim, Mi-Ae', 'Shin, Seungwoo', 'Park, Jong-Sook', 'Chang, Hun Soo', 'Cho, You Sook', 'Park, Hae-Sim', 'Park, Choon-Sik', 'Min, Zhang', 'Yoon, Seo Hee', 'Sol, In Suk', 'a Park, Young', 'Kim, Yoon Hee', 'Kim, Min Jung', 'Kim, Kyung Won', 'Sohn, Myung Hyun', 'Kim, Kyu-Earn', 'Shiquan, Wu', 'Lee, Yongwon', 'Bak, Hana', 'Ching, Maricar Wisco', 'Ramos, John Donnie', 'Jeong, Kyunguk', 'Lee, Sooyoung', 'Ahn, Kangmo', 'Sohn, Myung Hyun', 'Kim, Kyung Won', 'Lee, So-Yeon', 'Song, Tae Won', 'Jeon, Youhoon', 'Kim, Jihyun', 'Min, Taek Ki', 'Kim, Kyu-Earn', 'Pyun, Bok-Yang', 'Yang, Hyeon-Jong', 'Lee, Hae Ran', 'Ahn, Youngmin', 'Kwon, Ji-Won', 'Lim, Dae Hyun', 'Kim, Jeong Hee', 'Suh, Dongin', 'Ki, Hyung Young', 'Jeong, Kyunguk', 'Park, Byeong Sub', 'Lee, Sooyoung', 'Jeon, Se-Ah', 'Park, Kyu Jung', 'Yang, Song-I', 'Lee, Eun', 'Cho, Hyun-Ju', 'Kim, Young-Ho', 'Kang, Mi-Jin', 'Choi, Yean Jung', 'Choi, Kil Yong', 'Shin, Youn Ho', 'Ahn, Kangmo', 'Kim, Kyung Won', 'Kim, Byoung-Ju', 'Lee, So-Yeon', 'K, Eun-Jin', 'Dario, Roccatello', 'Liao, Jing', 'Feng, Yong', 'Shang, Yunxiao', 'Lee, Yongwon', 'Bak, Hana', 'Kim, Hyung Young', 'Kim, Byoung-Ju', 'Kwon, Ji-Won', 'Seo, Ju-Hee', 'Lee, Eun', 'Lee, So-Yeon', 'Yang, Song-I', 'Jung, Young-Ho', 'Kim, Hyo-Bin', 'Kwon, Ho-Jang', 'Park, Hee Ju', 'Min, Zhang', 'Guang-Min, Nong', 'Min, Jiang', 'Hur, Gyu Young', 'Sim, Eun Jung', 'Yoon, Sora', 'Choi, Juwhan', 'Kim, Junga', 'Sim, Jae Keom', 'Oh, Jee Youn', 'Jeong, Kyunguk', 'Park, Byeong Sub', 'Lee, Jeong-Min', 'Lee, Sooyoung', 'Cheon, Eunjae', 'Na, Youngjoo', 'Park, Kyu Jung', 'Lee, Eunjoo', 'Yang, William', 'Kelly, Suzanne', 'Perrins, Rob', 'Yang, Jimmy', 'Yang, William', 'Kelly, Suzanne', 'Perrins, Rob', 'Karsh, Jacob', 'Yang, Jimmy', 'Badellino, Hector', 'Teijeiro, Alvaro', 'Cuello, Mabel', 'Pereira, Marilyn Urrutia', 'Egues, Gustavo', 'Aktas, Ayse', 'Chun, Jin-Kyong', 'Mujuru, Hilda Angela', 'Sibanda, Elopy N.', 'Popescu, Andreea Ioana', 'Greblescu, Raluca', 'Rahman, Suheyla', 'Aktas, Ayse', 'Tataurshchikova, Nataly', 'Dissanayake, Eishika', 'Inoue, Yuzaburo', 'Shimojo, Naoki', 'Nakano, Taiji', 'Tanjung, Conny', 'Jensen-Jarolim, Erika', 'Fazekas, Judit', 'Singer, Josef', 'Lukschal, Anna', 'Horvat, Reinhard', 'Achatz-Straussberger, Gertrude', 'Achatz, Gernot', 'Fujita, Yuji', 'Ikegami, Shuji', 'Nakamura, Yoshitaka', 'Inoue, Yuzaburo', 'Shimojo, Naoki', 'Kohno, Yoichi', 'Suzuki, Shuichi', 'Ozawa, Naoko', 'Kubota, Takayuki', 'Nonaka, Ken', 'Ohara, Osamu', 'Masuda, Kentaro', 'Rhee, Chin Kook', 'Lee, Sook Young', 'Lee, Hwa Young', 'Lee, Hea Yon', 'Kang, Ji Young', 'Kim, Sei Won', 'Kwon, Soon Seog', 'Kim, Young Kyoon', 'Kim, Gun-Woo', 'Kim, Ju-Young', 'Cho, Sang-Heon', 'Cho, Sang-Heon', 'Kang, Hye-Ryun', 'Kang, Hye-Ryun', 'Kim, Hyo-Soo', 'Han, Jung Gyu', 'Lee, Jin', 'Lee, Ji Young', 'Go, Ji Young', 'Park, So Jung', 'Kim-Chang, Julie', 'Love, Cassandra', 'Lugar, Patricia', 'Citraresmi, Endah', 'Kaswandani, Nastiti', 'Utami, Cynthia', 'Said, Mardjanis', 'Jung, Young-Ho', 'Yang, Song-I', 'Kim, Byoung-Ju', 'Kwon, Ji-Won', 'Kim, Hwan-Cheol', 'Leem, Jong-Han', 'Seo, Ju-Hee', 'Kim, Hyung Young', 'Lee, So-Yeon', 'Kwon, Ho-Jang', 'Kim, Hyo-Bin', 'Cho, Hyun-Ju', 'Yamazaki, Susumu', 'Nakano, Nobuhiro', 'Honjoh, Asuka', 'Inage, Eisuke', 'Baba, Yosuke', 'Ohtsuka, Yoshikazu', 'Shimizu, Toshiaki', 'M., Ishaq', 'Khan, Sameera M. I.', 'Khan, Imran', 'Khan, Sabeen', 'Loo, Evelyn Xiu Ling', 'Goh, Anne', 'Teoh, Oon Hoe', 'Chan, Yiong Huak', 'Saw, Seang Mei', 'Kwek, Kenneth', 'Gluckman, Peter D', 'Godfrey, Keith M', 'Van Bever, Hugo', 'Chong, Yap Seng', 'Lee, Bee Wah', 'Shek, Lynette', 'Lee, Alison Joanne', 'Rossi, Daniela', 'Nemeth, Agnes', 'Sehlinger, Torsten', 'Bergmann, Karl-Christian', 'Goergen, Frank', 'Ehlayel, Mohammad S.', 'Bener, Abdul Bari', 'Chu, Hieu Chi', 'Do, Nga Thi Quynh', 'Van Nguyen, Dinh', 'Nguyen, Ha Thi Thu', 'Le, Huong Thi Minh', 'Van Nunen, Sheryl', 'Vidal, Christopher', 'Fernando, Suran', 'Psarros, Fotis', 'Syrigou, Ekaterini', 'Politi, Ekaterini', 'Chrysoulakis, Spyridon', 'Vourdas, Dimitrios', 'Petalas, Konstantinos', 'Saha, Mouli', 'Bhattacharya, Kashinath', 'Jain, Subir', 'Song, Xiaolian', 'Lin, Haiyan', 'Nishikawa, Kyohei', 'Shimada, Takashi', 'Yasueda, Hiroshi', 'Enomoto, Tadao', 'Aizawa, Daisuke', 'Kobayashi, Takayoshi', 'R., Chellaa', 'Jain, Subir', 'Jain, Subir', 'Yudina, Marina', 'M., Ishaq', 'Khan, Sameera M. I.', 'Khan, Imran', 'Khan, Sabeen', 'Saito, Mayako', 'Sari, Nurul Iman Nilam', 'Kim, Jae Young', 'Song, Jaechul', 'Kim, Inah', 'Lee, Kyeong Joon', 'Park, Soo Jin', 'Roh, Soo Yong', 'Billamay, Somxay', 'Udin, Muchammad Fahrul', 'Han, Mae Ja', 'Oh, Jae-Won', 'Kim, Kyu Rang', 'Kim, Baek-Jo', 'Mazza, Jorge A.', 'Ko, Jason Kangeun', 'Huang, David J. T.', 'Furuya, Kanae', 'Kainuma, Keigo', 'Ito, Takahiro', 'Nagao, Mizuho', 'Fujisawa, Takao', 'Hirayama, Junya', 'Kuwahara, Yu', 'Qualizza, Rosanna', 'Incorvaia, Cristoforo', 'Maraschini, Anna', 'Hasnain, Syed Mohammed', 'Al-Frayh, Abdulrahman', 'Hartog, Anita', 'Bastiaans, Jacqueline', 'Loonstra, Reinilde', 'Rutten, Lieke', 'Harthoorn, Lucien', 'Van Bergenhenegouwen, Jeroen', 'Garssen, Johan', 'Yoo, Kwang-Ha', 'Cho, Sang-Heon', 'Ghoshal, AG', 'Muttalif, Abdul Razak Bin Abdul', 'Lin, Horng- Chyuan', 'Thanaviratananich, Sanguansak', 'Bagga, Shalini', 'Faruqi, Rab', 'Baidya, Santwona', 'Taylor, Colman', 'Wang, De Yun', 'Ahn, Hae-Ryun', 'Hong, Soon-Kwan', 'Kim, Jong-Woong', 'Nam, Gui-Hyun', 'Kim, Mee-Ja', 'Park, Jae-Kyoung', 'Yi, Myung-Hee', 'Jeong, Kyoung Yong', 'Kim, Ju-Yeong', 'Yong, Tai-Soon', 'Kim, Bum Joon', 'Joo, Hs', 'Lim, Kj', 'Lee, Jae-Hyun', 'Park, Jung-Won', 'Yoon, Kh', 'Choi, DS', 'Joo, Hanseung', 'Kim, Bum Joon', 'Lim, Kj', 'Kim, MJ', 'Choi, DS', 'Yoon, Kh', 'Kim, Bum Joon', 'Joo, Hanseung', 'Jung, Woo Sang', 'Lim, Kj', 'Choi, DS', 'Lee, Ji-Hoon', 'Kwon, Soon-Chan', 'Lee, Soo-Jin', 'Roh, Soo Yong', 'Kim, Hogil', 'Lee, Kyeong Joon', 'Van De Loo, Aurora', 'Fernstrand, Amanda', 'Garssen, Johan', 'Verster, Joris', 'Van De Loo, Aurora', 'Garssen, Johan', 'Verster, Joris', 'Golez, Jasmina', 'Ozasa, Koji', 'Kuroda, Etsushi', 'Ishii, Ken', 'Imran, Muhammad', 'Gierer, Selina', 'Martinez, John', 'Wong, Lydia', 'Lee, Bee Wah', 'Yap, Gaik Chin', 'Llanora, Genevieve', 'Thong, Bernard', 'Shek, Lynette', 'Ehlayel, Mohammad S.', 'Soliman, Ashraf', 'Martins, Pedro', 'Marques, João', 'Gomes-Belo, Joana', 'Palmeiro, Teresa', 'Caires, Iolanda', 'Belo, Joana', 'Botelho, Maria Amália', 'Leiria-Pinto, Paula', 'Neuparth, Nuno', 'Suratannon, Narissara', 'Mekaroonkamol, Jaichat', 'Ngamphaiboon, Jarungchit', 'Lertchanaruengrith, Piyawadee', 'Chatchatee, Pantipa', 'Kardar, Gholamali', 'Majd, Ahmad', 'Shahali, Youcef', 'Ghahremaninejad, Farrokh', 'Pourpak, Zahra', 'Mousavi, Fateme', 'Sadeghi-Shabestari, Mahnaz', 'Van Bilsen, K.', 'Manusama, O.', 'Dik, W.a.', 'Van Der Burg, M.', 'Van Der Velden, V. H. J.', 'Dalm, V.a.S. H.', 'Van Hagen, P. M.', 'Liu, Yongping', 'Jeong, Yi Yeong', 'Kim, Ji Hye', 'Yoon, Moon Gyeong', 'Ye, Young Min', 'Shin, Yoo Seob', 'Ban, Ga Young', 'Park, Hae-Sim', 'Jung, Hye Min', 'Roh, Soo Yong', 'Song, Jaechul', 'Lee, Ji-Hoon', 'Kim, Hogil', 'Kim, Jae Young', 'Lee, Kyeong Joon', 'Wong, Lydia', 'Rajakulendran, Mohana', 'Santhanam, Haripriya', 'Shek, Lynette', 'Lim, Tow Keang', 'Kim, Hogil', 'Lee, Soo-Jin', 'Lee, Ji-Hoon', 'Roh, Soo Yong', 'Kwon, Soon-Chan', 'Wistiani, Ani', 'H, Galuh', 'Kardar, Gholam Ali', 'Sharifshoushtari, Maryam', 'Majd, Ahmad', 'Nejadsattari, Taher', 'Pourpak, Zahra', 'Moin, Mostafa', 'Kim, Ji Hye', 'Seo, Daehong', 'Ye, Young Min', 'Park, Hae-Sim', 'Park, Jung-Won', 'Lee, Jae-Hyun', 'Shin, Yoo Seob', 'Kowalski, Marek L.', 'Wardzynska, Aleksandra', 'Kurowski, Marcin', 'Pawelczyk, Malgorzata/Ewa', 'Wysokinski, Adam', 'Kloszewska, Iwona', 'Grzegorczyk, Janina', 'Piotrowski, Wojciech', 'Makowska, Joanna', 'Kwon, Soon-Chan', 'Song, Jaechul', 'Kim, Yong-Kyu', 'Bostanci, Ilknur', 'Emeksiz, Zeynep Sengul', 'Ertugrul, Aysegul', 'Ozmen, Serap', 'Sahin, Soner', 'Kim, Sang-Ha', 'Lee, Myoung Kyu', 'Lee, Won Yeon', 'Yong, Suk Joong', 'Lee, Seok Jeong', 'Jung, Ye-Ryung', 'Kim, Myung Shin', 'Park, Jong-Sook', 'Jang, An-Soo', 'Park, Choon-Sik', 'Wulandari, Diah Asri', 'Kartasasmita, Cissy', 'Yani, Finny Fitry', 'Machmud, Rizanda', 'Lestari, Dhina Lydia', 'Rusdi, Rusdi', 'Yurmalina, Yurmalina', 'Darwin, Eryati', 'Bostanci, Ilknur', 'Karacan, Gulin', 'Ercan, Nazli', 'Colak, Asuman', 'Alisik, Murat', 'Basarir, Gulay', 'Erel, Ozcan', 'Bostanci, Ilknur', 'Keskin, Yasemin', 'Lopata, Andreas/Ludwig', 'Zenger, Kyall', 'Nugraha, Roni', 'Kamath, Sandip', 'Bielory, Leonard', 'Georgopoulos, Panos', 'Zhang, Yong', 'Mi, Wheat', 'Cai, Ting', 'Xian, MO', 'Li, Jing', 'Feng, Mulin']",World Allergy Organ J,,,True
f39671c6a9f5a19d6db58094f4a8f07f6e036085,PMC,The host immune response in respiratory virus infection: balancing virus clearance and immunopathology,http://dx.doi.org/10.1007/s00281-016-0558-0,PMC4896975,26965109,CC BY,"The respiratory tract is constantly exposed to the external environment, and therefore, must be equipped to respond to and eliminate pathogens. Viral clearance and resolution of infection requires a complex, multi-faceted response initiated by resident respiratory tract cells and innate immune cells and ultimately resolved by adaptive immune cells. Although an effective immune response to eliminate viral pathogens is essential, a prolonged or exaggerated response can damage the respiratory tract. Immune-mediated pulmonary damage is manifested clinically in a variety of ways depending on location and extent of injury. Thus, the antiviral immune response represents a balancing act between the elimination of virus and immune-mediated pulmonary injury. In this review, we highlight major components of the host response to acute viral infection and their role in contributing to mitigating respiratory damage. We also briefly describe common clinical manifestations of respiratory viral infection and morphological correlates. The continuing threat posed by pandemic influenza as well as the emergence of novel respiratory viruses also capable of producing severe acute lung injury such as SARS-CoV, MERS-CoV, and enterovirus D68, highlights the need for an understanding of the immune mechanisms that contribute to virus elimination and immune-mediated injury.",2016 Mar 10,"['Newton, Amy H.', 'Cardani, Amber', 'Braciale, Thomas J.']",Semin Immunopathol,,,True
d78837afeedbb3c9dfa91a675aa03d34ef5a4387,PMC,The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation,http://dx.doi.org/10.1007/s00281-016-0555-3,PMC4896990,26957481,CC BY,"Acute and chronic inflammatory responses in the lung are associated with the accumulation of large quantities of immune and structural cells undergoing apoptosis, which need to be engulfed by phagocytes in a process called ‘efferocytosis’. Apoptotic cell recognition and removal from the lung is mediated predominantly by airway macrophages, though immature dendritic cells and non-professional phagocytes, such as epithelial cells and mesenchymal cells, can also display this function. Efficient clearance of apoptotic cells from the airways is essential for successful resolution of inflammation and the return to lung homeostasis. Disruption of this process leads to secondary necrosis of accumulating apoptotic cells, release of necrotic cell debris and subsequent uncontrolled inflammatory activation of the innate immune system by the released ‘damage associated molecular patterns’ (DAMPS). To control the duration of the immune response and prevent autoimmune reactions, anti-inflammatory signalling cascades are initiated in the phagocyte upon apoptotic cell uptake, mediated by a range of receptors that recognise specific phospholipids or proteins externalised on, or secreted by, the apoptotic cell. However, prolonged activation of apoptotic cell recognition receptors, such as the family of receptor tyrosine kinases Tyro3, Axl and MerTK (TAM), may delay or prevent inflammatory responses to subsequent infections. In this review, we will discuss recent advances in our understanding of the mechanism controlling apoptotic cell recognition and removal from the lung in homeostasis and during inflammation, the contribution of defective efferocytosis to chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease, asthma and cystic fibrosis, and implications of the signals triggered by apoptotic cells in the susceptibility to pulmonary microbial infections.",2016 Mar 8,"['Grabiec, Aleksander M.', 'Hussell, Tracy']",Semin Immunopathol,,,True
1699f74dc5e3e5ee7417778d18f7f5a46fb7c879,PMC,Equine rhinitis B viruses in horse fecal samples from the Middle East,http://dx.doi.org/10.1186/s12985-016-0547-x,PMC4897857,27267372,CC BY,"BACKGROUND: Among all known picornaviruses, only two species, equine rhinitis A virus and equine rhinitis B virus (ERBV) are known to infect horses, causing respiratory infections. No reports have described the detection of ERBV in fecal samples of horses and no complete genome sequences of ERBV3 are available. METHODS: We performed a molecular epidemiology study to detect ERBVs in horses from Dubai and Hong Kong. Complete genome sequencing of the ERBVs as well as viral loads and genome, phylogenetic and evolutionary analysis were performed on the positive samples. RESULTS: ERBV was detected in four (13.8 %) of the 29 fecal samples in horses from Dubai, with viral loads 8.28 × 10(3) to 5.83 × 10(4) copies per ml, but none of the 47 fecal samples in horses from Hong Kong by RT-PCR. Complete genome sequencing and phylogenetic analysis showed that three of the four strains were ERBV3 and one was ERBV2. The major difference between the genomes of ERBV3 and those of ERBV1 and ERBV2 lied in the amino acid sequences of their VP1 proteins. The Ka/Ks ratios of all the coding regions in the ERBV3 genomes were all <0.1, suggesting that ERBV3 were stably evolving in horses. Using the uncorrelated lognormal distributed relaxed clock model on VP1 gene, the date of the most recent common ancestor (MRCA) of ERBV3 was estimated to be 1785 (HPDs, 1176 to 1937) and the MRCA dates of ERBV1 and ERBV2 were estimated to be 1848 (HPDs, 1466 to 1949) respectively. CONCLUSIONS: Both acid stable (ERBV3) and acid labile (ERBV2) ERBVs could be found in fecal samples of horses. Detection of ERBVs in fecal samples would have implications for their transmission and potential role in gastrointestinal diseases as well as fecal sampling as an alternative method of identifying infected horses.",2016 Jun 7,"['Woo, Patrick C. Y.', 'Lau, Susanna K. P.', 'Choi, Garnet K. Y.', 'Huang, Yi', 'Wernery, Renate', 'Joseph, Sunitha', 'Wong, Emily Y. M.', 'Elizabeth, Shyna K.', 'Patteril, Nissy Annie Georgy', 'Li, Tong', 'Wernery, Ulrich', 'Yuen, Kwok-Yung']",Virol J,,,True
9a679e9fdf3590b7f9204c3dc3ff6307c3d4642b,PMC,Global research trends of Middle East respiratory syndrome coronavirus: a bibliometric analysis,http://dx.doi.org/10.1186/s12879-016-1600-5,PMC4897912,27267256,CC BY,"BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is a virus that causes severe viral pneumonia in humans, known to have a high mortality rate and a similarity in clinical symptoms with severe acute respiratory syndrome coronavirus. It was first isolated in Kingdom of Saudi Arabia (KSA) in 2012 and after that, MERS-CoV exhibited outbreaks in several regions of the world. This study aimed to assess the characteristics of publications involving MERS-CoV at global level by using a bibliometric analysis. METHODS: Scopus database was searched on March 4, 2016 for MERS-CoV publications published between 2012 and 2015. It was performed on the same day in order to avoid the possible bias came from update on the database because the metrics are changing over time. All publication types were considered; however publications as errata were excluded. Analysis parameters include year of publication, publication type, patterns of international collaboration, research institutions, journals, impact factor, h-index, language, and times cited. RESULTS: A total of 883 MERS-CoV research publications were published across the world. The MERS-CoV-associated publications were originated from 92 countries/territories, indicating the international spread of MERS-CoV research. The USA was the largest contributor, with 319 articles published over 4 years, followed by KSA (113 articles). The total number of citations for these publications has already achieved 8,015, with an average of 9.01 citations per each publication. The h-index for MERS-CoV-associated publications was 48. The USA also have the highest h-index (32), followed by KSA (26) and UK (22). Netherland produced the greatest proportion of publications with international research collaboration (72.7 %) followed by the UK (71 %) and Germany (69.1 %) out of the total number of publications for each country. CONCLUSIONS: There is a rapid increase in research activities related to MERS-CoV from 2012 to 2015. This study demonstrates that the MERS-CoV related literature has grown to be more extensive and global over the past 4 years. The bulk of publications in the field of MERS-CoV research are published by high-income countries such as the USA. Furthermore, the USA, the UK and KSA may have higher quality of articles according to the value of h-index.",2016 Jun 7,"Zyoud, Sa’ed H.",BMC Infect Dis,,,True
8a58dd3509470bd8a8a25fa473991ca6681066d9,PMC,Development of monoclonal antibodies and serological assays including indirect ELISA and fluorescent microsphere immunoassays for diagnosis of porcine deltacoronavirus,http://dx.doi.org/10.1186/s12917-016-0716-6,PMC4898321,27277214,CC BY,"BACKGROUND: A novel porcine deltacoronavirus (PDCoV), also known as porcine coronavirus HKU15, was reported in China in 2012 and identified in the U.S. in early 2014. Since then, PDCoV has been identified in a number of U.S. states and linked with clinical disease including acute diarrhea and vomiting in the absence of other identifiable pathogens. Since PDCoV was just recently linked with clinical disease, few specific antibody-based reagents were available to assist in diagnosis of PDCoV and limited serological capabilities were available to detect an antibody response to this virus. Therefore, the overall objective of this project was to develop and validate selected diagnostic reagents and assays for PDCoV antigen and antibody detection. RESULTS: The nucleoprotein of PDCoV was expressed as a recombinant protein and purified for use as an antigen to immunize mice for polyclonal, hyperimmune sera and monoclonal antibody (mAb) production. The resulting mAbs were evaluated for use in fluorescent antibody staining methods to detect PDCoV infected cells following virus isolation attempts and for immunohistochemistry staining of intestinal tissues of infected pigs. The same antigen was used to develop serological tests to detect the antibody response to PDCoV in pigs following infection. Serum samples from swine herds with recent documentation of PDCoV infection and samples from expected naïve herds were used for initial assay optimization. The tests were optimized in a checkerboard fashion to reduce signal to noise ratios using samples of known status. Statistical analysis was performed to establish assay cutoff values and assess diagnostic sensitivities and specificities. At least 629 known negative serum samples and 311 known positive samples were evaluated for each assay. The enzyme linked immunosorbent assay (ELISA) showed diagnostic sensitivity (DSe) of 96.1 % and diagnostic specificity (DSp) of 96.2 %. The fluorescent microsphere immunoassay (FMIA) showed a DSe of 95.8 % and DSp of 98.1 %. Both ELISA and FMIA detected seroconversion of challenged pigs between 8–14 days post-infection (DPI). An indirect fluorescent antibody (IFA) test was also developed using cell culture adapted PDCoV for comparative purposes. CONCLUSION: These new, specific reagents and serological assays will allow for improved diagnosis of PDCoV. Since many aspects of PDCoV infection and transmission are still not fully understood, the reagents and assays developed in this project should provide valuable tools to help understand this disease and to aid in the control and surveillance of porcine deltacoronavirus outbreaks.",2016 Jun 8,"['Okda, Faten', 'Lawson, Steven', 'Liu, Xiaodong', 'Singrey, Aaron', 'Clement, Travis', 'Hain, Kyle', 'Nelson, Julie', 'Christopher-Hennings, Jane', 'Nelson, Eric A.']",BMC Vet Res,,,True
b4ced0e08f5b03e84a5addaaf3557b3cdc1ef277,PMC,Nucleotide composition of the Zika virus RNA genome and its codon usage,http://dx.doi.org/10.1186/s12985-016-0551-1,PMC4898363,27278486,CC BY,"BACKGROUND: RNA viruses have genomes with a distinct nucleotide composition and codon usage. We present the global characteristics of the RNA genome of Zika virus (ZIKV), an emerging pathogen within the Flavivirus genus. ZIKV was first isolated in 1947 in Uganda, caused a widespread epidemic in South and Central America and the Caribbean in 2015 and has recently been associated with microcephaly in newborns. METHODS: The nearly 11 kb positive-stranded RNA genome of ZIKV was analyzed for its nucleotide composition, also in the context of the folded RNA molecule. Nucleotide trends were investigated along the genome length by skew analyses and we analyzed the codons used for translation of the ZIKV proteins. RESULTS: ZIKV RNA has a biased nucleotide composition in being purine-rich and pyrimidine-poor. This preference for purines is a general characteristic of the mosquito-borne and tick-borne flaviviruses. The virus-specific nucleotide bias is further enriched in the unpaired, single-stranded regions of the structured ZIKV RNA genome, thus further imposing this ZIKV-specific signature. The codons used for translation of the ZIKV proteins is also unusual, but we show that it is the underlying bias in nucleotide composition of the viral RNA that largely dictates these codon preferences. CONCLUSIONS: The ZIKV RNA genome has a biased nucleotide composition that dictates the codon usage of this flavivirus. We discuss the evolutionary scenarios and molecular mechanisms that may be responsible for these distinctive ZIKV RNA genome features.",2016 Jun 8,"['van Hemert, Formijn', 'Berkhout, Ben']",Virol J,,,True
d90382cb2b05e6761cea35d274213ee4f5c0cd02,PMC,Assessment of pathogenicity and tissue distribution of infectious bronchitis virus strains (Italy 02 genotype) isolated from moroccan broiler chickens,http://dx.doi.org/10.1186/s12917-016-0711-y,PMC4898447,27277076,CC BY,"BACKGROUND: Avian infectious bronchitis (IB) is one of the most important viral diseases of poultry, affecting chickens of all ages and causing major economic losses in poultry flocks. Mass vaccination is conducted in Morocco using a vaccine against Massachusetts, which is the most dominant serotype; however no information about the pathogenesis and tissue distribution of the Moroccan Italy 02 genotype was reported. 40 one-day-old specific pathogen free chickens were divided randomly into four groups. Group1, 2 and 3 were inoculated intra oculo-nasally with 103.5 EID50 of Italy02 viruses, and group 4 was kept as control. Chickens in each group were monitored for 14 days post-infection (pi). RESULTS: Chickens in all infected groups showed severe respiratory signs, which most of them have been reproduced on 2dpi, with varying times of appearance and disappearance. The infected birds appeared lethargic, reluctant to move, with specific respiratory clinical signs and macroscopic lesions. However no nephritis lesions or mortality were recorded in all groups. The specific histological lesions finding in all infected birds, exhibited tracheal lesions with mucosal thickening, hyperplasia of the surface epithelium, mononuclear inflammatory cell infiltrate of lamina propria. Primary and secondary bronchi, epithelial hyperplasia and mononuclear inflammatory cell infiltrate of the lamina propria were also observed. Tracheal lesions developed in all infected birds, confirm the ability of the three tested strains to induce respiratory disease. The results at 14 dpi also revealed that all strains were able to induce serological response. Virus re-isolation from infected organs and amplification of the viral RNA by real-time PCR proved the presence of the virus in lung and trachea of infected chicks. Neither re-isolation nor significant viral RNA detection were detected in the kidney. CONCLUSION: The results demonstrated that the three strains Italy02 genotype emerging in Moroccan poultry farms have a wide distribution for respiratory system, without kidney damage and without causing mortality.",2016 Jun 8,"['Khataby, Khadija', 'Kichou, Faouzi', 'Loutfi, Chafiqa', 'Ennaji, My Mustapha']",BMC Vet Res,,,True
1f4d59790ebb50fad78486e25156bcbb6b1edb40,PMC,Identify-Isolate-Inform: A Tool for Initial Detection and Management of Zika Virus Patients in the Emergency Department,http://dx.doi.org/10.5811/westjem.2016.3.30188,PMC4899052,27330653,CC BY,"First isolated in 1947 from a monkey in the Zika forest in Uganda, and from mosquitoes in the same forest the following year, Zika virus has gained international attention due to concerns for infection in pregnant women potentially causing fetal microcephaly. More than one million people have been infected since the appearance of the virus in Brazil in 2015. Approximately 80% of infected patients are asymptomatic. An association with microcephaly and other birth defects as well as Guillain-Barre Syndrome has led to a World Health Organization declaration of Zika virus as a Public Health Emergency of International Concern in February 2016. Zika virus is a vector-borne disease transmitted primarily by the Aedes aegypti mosquito. Male to female sexual transmission has been reported and there is potential for transmission via blood transfusions. After an incubation period of 2–7 days, symptomatic patients develop rapid onset fever, maculopapular rash, arthralgia, and conjunctivitis, often associated with headache and myalgias. Emergency department (ED) personnel must be prepared to address concerns from patients presenting with symptoms consistent with acute Zika virus infection, especially those who are pregnant or planning travel to Zika-endemic regions, as well as those women planning to become pregnant and their partners. The identify-isolate-inform (3I) tool, originally conceived for initial detection and management of Ebola virus disease patients in the ED, and later adjusted for measles and Middle East Respiratory Syndrome, can be adapted for real-time use for any emerging infectious disease. This paper reports a modification of the 3I tool for initial detection and management of patients under investigation for Zika virus. Following an assessment of epidemiologic risk, including travel to countries with mosquitoes that transmit Zika virus, patients are further investigated if clinically indicated. If after a rapid evaluation, Zika or other arthropod-borne diseases are the only concern, isolation (contact, droplet, airborne) is unnecessary. Zika is a reportable disease and thus appropriate health authorities must be notified. The modified 3I tool will facilitate rapid analysis and triggering of appropriate actions for patients presenting to the ED at risk for Zika.",2016 May 4,"['Koenig, Kristi L.', 'Almadhyan, Abdulmajeed', 'Burns, Michael J.']",West J Emerg Med,,,True
e788ce631ca8a7d0a0d0b48dfd06d343de282972,PMC,The Ebola Virus Disease Outbreak in West Africa: A Wake-up Call to Revitalize Implementation of the International Health Regulations,http://dx.doi.org/10.3389/fpubh.2016.00120,PMC4899437,27376056,CC BY,"The 2014/15 Ebola virus disease (EVD) outbreak in West Africa has highlighted the inherent weaknesses associated with the implementation of the International Health Regulations (IHR). In this perspective article, the lessons learnt from the outbreak are used to review the challenges impeding effective implementation of the IHR and to propose policy and strategic options for enhancing its application. While some progress has been achieved in implementing the IHR in several countries, numerous challenges continue to impede its effectiveness, especially in developing countries, such as those affected by the West Africa EVD outbreak. Political and economic sensitivities associated with reporting public health emergencies of international concern (PHEIC), inadequate resources (human and financial), and lack of technical know-how required for implementation of the IHR are weaknesses that continue to constrain the implementation of the regulations. In view of the complex sociopolitical, cultural, and public health dimensions of PHEICs, frameworks, such as the IHR, which have legal backing, seem to be the most effective and sustainable option for assuring timely detection, notification, and response to such events. Renewed efforts to strengthen national and global institutional frameworks for implementation of the IHR are therefore required. Improvements in transparency, commitment, and accountability of parties to the IHR, mainstreaming of the IHR into national public health governance structures, use of multidisciplinary approaches, and mobilization of the required resources for the implementation of the IHR are imperative.",2016 Jun 9,"Olu, Olushayo Oluseun",Front Public Health,,,True
491f000353cbe2d030d16077ecb01f02d7c6bf3f,PMC,Development of a Rapid Point-of-Use DNA Test for the Screening of Genuity® Roundup Ready 2 Yield® Soybean in Seed Samples,http://dx.doi.org/10.1155/2016/3145921,PMC4899603,27314015,CC BY,"Testing for the presence of genetically modified material in seed samples is of critical importance for all stakeholders in the agricultural industry, including growers, seed manufacturers, and regulatory bodies. While rapid antibody-based testing for the transgenic protein has fulfilled this need in the past, the introduction of new variants of a given transgene demands new diagnostic regimen that allows distinguishing different traits at the nucleic acid level. Although such molecular tests can be performed by PCR in the laboratory, their requirement for expensive equipment and sophisticated operation have prevented its uptake in point-of-use applications. A recently developed isothermal DNA amplification technique, recombinase polymerase amplification (RPA), combines simple sample preparation and amplification work-flow procedures with the use of minimal detection equipment in real time. Here, we report the development of a highly sensitive and specific RPA-based detection system for Genuity Roundup Ready 2 Yield (RR2Y) material in soybean (Glycine max) seed samples and present the results of studies applying the method in both laboratory and field-type settings.",2016 May 26,"['Chandu, Dilip', 'Paul, Sudakshina', 'Parker, Mathew', 'Dudin, Yelena', 'King-Sitzes, Jennifer', 'Perez, Tim', 'Mittanck, Don W.', 'Shah, Manali', 'Glenn, Kevin C.', 'Piepenburg, Olaf']",Biomed Res Int,,,True
2aabf3a6ba52bfdd83a884673fd6e48c67b8727b,PMC,Host genetics determine susceptibility to avian influenza infection and transmission dynamics,http://dx.doi.org/10.1038/srep26787,PMC4899695,27279280,CC BY,"Host-genetic control of influenza virus infection has been the object of little attention. In this study we determined that two inbred lines of chicken differing in their genetic background , Lines 0 and C-B12, were respectively relatively resistant and susceptible to infection with the low pathogenicity influenza virus A/Turkey/England/647/77 as defined by substantial differences in viral shedding trajectories. Resistant birds, although infected, were unable to transmit virus to contact birds, as ultimately only the presence of a sustained cloacal shedding (and not oropharyngeal shedding) was critical for transmission. Restriction of within-bird transmission of virus occurred in the resistant line, with intra-nares or cloacal infection resulting in only local shedding and failing to transmit fully through the gastro-intestinal-pulmonary tract. Resistance to infection was independent of adaptive immune responses, including the expansion of specific IFNγ secreting cells or production of influenza-specific antibody. Genetic resistance to a novel H9N2 virus was less robust, though significant differences between host genotypes were still clearly evident. The existence of host-genetic determination of the outcome of influenza infection offers tools for the further dissection of this regulation and also for understanding the mechanisms of influenza transmission within and between birds.",2016 Jun 9,"['Ruiz-Hernandez, Raul', 'Mwangi, William', 'Peroval, Marylene', 'Sadeyen, Jean-Remy', 'Ascough, Stephanie', 'Balkissoon, Devanand', 'Staines, Karen', 'Boyd, Amy', 'McCauley, John', 'Smith, Adrian', 'Butter, Colin']",Sci Rep,,,True
f5c62862db786a73879e9160076587d107dbe6e8,PMC,Host genetics determine susceptibility to avian influenza infection and transmission dynamics,http://dx.doi.org/10.1038/srep26787,PMC4899695,27279280,CC BY,"Host-genetic control of influenza virus infection has been the object of little attention. In this study we determined that two inbred lines of chicken differing in their genetic background , Lines 0 and C-B12, were respectively relatively resistant and susceptible to infection with the low pathogenicity influenza virus A/Turkey/England/647/77 as defined by substantial differences in viral shedding trajectories. Resistant birds, although infected, were unable to transmit virus to contact birds, as ultimately only the presence of a sustained cloacal shedding (and not oropharyngeal shedding) was critical for transmission. Restriction of within-bird transmission of virus occurred in the resistant line, with intra-nares or cloacal infection resulting in only local shedding and failing to transmit fully through the gastro-intestinal-pulmonary tract. Resistance to infection was independent of adaptive immune responses, including the expansion of specific IFNγ secreting cells or production of influenza-specific antibody. Genetic resistance to a novel H9N2 virus was less robust, though significant differences between host genotypes were still clearly evident. The existence of host-genetic determination of the outcome of influenza infection offers tools for the further dissection of this regulation and also for understanding the mechanisms of influenza transmission within and between birds.",2016 Jun 9,"['Ruiz-Hernandez, Raul', 'Mwangi, William', 'Peroval, Marylene', 'Sadeyen, Jean-Remy', 'Ascough, Stephanie', 'Balkissoon, Devanand', 'Staines, Karen', 'Boyd, Amy', 'McCauley, John', 'Smith, Adrian', 'Butter, Colin']",Sci Rep,,,False
c8ca3a5306db10a7842b853031404ecbc0a363ed,PMC,"Genetic diversity, seasonality and transmission network of human metapneumovirus: identification of a unique sub-lineage of the fusion and attachment genes",http://dx.doi.org/10.1038/srep27730,PMC4899729,27279080,CC BY,"Human metapneumovirus (HMPV) is an important viral respiratory pathogen worldwide. Current knowledge regarding the genetic diversity, seasonality and transmission dynamics of HMPV among adults and children living in tropical climate remains limited. HMPV prevailed at 2.2% (n = 86/3,935) among individuals presented with acute respiratory tract infections in Kuala Lumpur, Malaysia between 2012 and 2014. Seasonal peaks were observed during the northeast monsoon season (November–April) and correlated with higher relative humidity and number of rainy days (P < 0.05). Phylogenetic analysis of the fusion and attachment genes identified the co-circulation of three known HMPV sub-lineages, A2b and B1 (30.2% each, 26/86) and B2 (20.9%, 18/86), with genotype shift from sub-lineage B1 to A2b observed in 2013. Interestingly, a previously unrecognized sub-lineage of A2 was identified in 18.6% (16/86) of the population. Using a custom script for network construction based on the TN93 pairwise genetic distance, we identified up to nine HMPV transmission clusters circulating as multiple sub-epidemics. Although no apparent major outbreak was observed, the increased frequency of transmission clusters (dyads) during seasonal peaks suggests the potential roles of transmission clusters in driving the spread of HMPV. Our findings provide essential information for therapeutic research, prevention strategies, and disease outbreak monitoring of HMPV.",2016 Jun 9,"['Chow, Wei Zhen', 'Chan, Yoke Fun', 'Oong, Xiang Yong', 'Ng, Liang Jie', 'Nor’E, Siti Sarah', 'Ng, Kim Tien', 'Chan, Kok Gan', 'Hanafi, Nik Sherina', 'Pang, Yong Kek', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Sci Rep,,,True
02a336a36902a4f44b72a881267d77fc79fd7da1,PMC,"Genetic diversity, seasonality and transmission network of human metapneumovirus: identification of a unique sub-lineage of the fusion and attachment genes",http://dx.doi.org/10.1038/srep27730,PMC4899729,27279080,CC BY,"Human metapneumovirus (HMPV) is an important viral respiratory pathogen worldwide. Current knowledge regarding the genetic diversity, seasonality and transmission dynamics of HMPV among adults and children living in tropical climate remains limited. HMPV prevailed at 2.2% (n = 86/3,935) among individuals presented with acute respiratory tract infections in Kuala Lumpur, Malaysia between 2012 and 2014. Seasonal peaks were observed during the northeast monsoon season (November–April) and correlated with higher relative humidity and number of rainy days (P < 0.05). Phylogenetic analysis of the fusion and attachment genes identified the co-circulation of three known HMPV sub-lineages, A2b and B1 (30.2% each, 26/86) and B2 (20.9%, 18/86), with genotype shift from sub-lineage B1 to A2b observed in 2013. Interestingly, a previously unrecognized sub-lineage of A2 was identified in 18.6% (16/86) of the population. Using a custom script for network construction based on the TN93 pairwise genetic distance, we identified up to nine HMPV transmission clusters circulating as multiple sub-epidemics. Although no apparent major outbreak was observed, the increased frequency of transmission clusters (dyads) during seasonal peaks suggests the potential roles of transmission clusters in driving the spread of HMPV. Our findings provide essential information for therapeutic research, prevention strategies, and disease outbreak monitoring of HMPV.",2016 Jun 9,"['Chow, Wei Zhen', 'Chan, Yoke Fun', 'Oong, Xiang Yong', 'Ng, Liang Jie', 'Nor’E, Siti Sarah', 'Ng, Kim Tien', 'Chan, Kok Gan', 'Hanafi, Nik Sherina', 'Pang, Yong Kek', 'Kamarulzaman, Adeeba', 'Tee, Kok Keng']",Sci Rep,,,False
c726b09add3a385ad9b4fa87e54130d78194dcd2,PMC,Duck gut viral metagenome analysis captures snapshot of viral diversity,http://dx.doi.org/10.1186/s13099-016-0113-5,PMC4899906,27284287,CC BY,"BACKGROUND: Ducks (Anas platyrhynchos) an economically important waterfowl for meat, eggs and feathers; is also a natural reservoir for influenza A viruses. The emergence of novel viruses is attributed to the status of co-existence of multiple types and subtypes of viruses in the reservoir hosts. For effective prediction of future viral epidemic or pandemic an in-depth understanding of the virome status in the key reservoir species is highly essential. METHODS: To obtain an unbiased measure of viral diversity in the enteric tract of ducks by viral metagenomic approach, we deep sequenced the viral nucleic acid extracted from cloacal swabs collected from the flock of 23 ducks which shared the water bodies with wild migratory birds. RESULT: In total 7,455,180 reads with average length of 146 bases were generated of which 7,354,300 reads were de novo assembled into 24,945 contigs with an average length of 220 bases and the remaining 100,880 reads were singletons. The duck virome were identified by sequence similarity comparisons of contigs and singletons (BLASTx E score, <10(−3)) against viral reference database. Numerous duck virome sequences were homologous to the animal virus of the Papillomaviridae family; and phages of the Caudovirales, Inoviridae, Tectiviridae, Microviridae families and unclassified phages. Further, several duck virome sequences had homologous with the insect viruses of the Poxviridae, Alphatetraviridae, Baculoviridae, Densovirinae, Iflaviridae and Dicistroviridae families; and plant viruses of the Secoviridae, Virgaviridae, Tombusviridae and Partitiviridae families, which reflects the diet and habitation of ducks. CONCLUSION: This study increases our understanding of the viral diversity and expands the knowledge about the spectrum of viruses harboured in the enteric tract of ducks.",2016 Jun 9,"['Fawaz, Mohammed', 'Vijayakumar, Periyasamy', 'Mishra, Anamika', 'Gandhale, Pradeep N.', 'Dutta, Rupam', 'Kamble, Nitin M.', 'Sudhakar, Shashi B.', 'Roychoudhary, Parimal', 'Kumar, Himanshu', 'Kulkarni, Diwakar D.', 'Raut, Ashwin Ashok']",Gut Pathog,,,True
3c51c5a11684d15c9f3d39dc99b0fdf9f7a73847,PMC,Cybercare 2.0: meeting the challenge of the global burden of disease in 2030,http://dx.doi.org/10.1007/s12553-016-0132-8,PMC4901101,27358760,CC BY,"In this paper, we propose to advance and transform today’s healthcare system using a model of networked health care called Cybercare. Cybercare means “health care in cyberspace” — for example, doctors consulting with patients via videoconferencing across a distributed network; or patients receiving care locally — in neighborhoods, “minute clinics,” and homes — using information technologies such as telemedicine, smartphones, and wearable sensors to link to tertiary medical specialists. This model contrasts with traditional health care, in which patients travel (often a great distance) to receive care from providers in a central hospital. The Cybercare model shifts health care provision from hospital to home; from specialist to generalist; and from treatment to prevention. Cybercare employs advanced technology to deliver services efficiently across the distributed network — for example, using telemedicine, wearable sensors and cell phones to link patients to specialists and upload their medical data in near-real time; using information technology (IT) to rapidly detect, track, and contain the spread of a global pandemic; or using cell phones to manage medical care in a disaster situation. Cybercare uses seven “pillars” of technology to provide medical care: genomics; telemedicine; robotics; simulation, including virtual and augmented reality; artificial intelligence (AI), including intelligent agents; the electronic medical record (EMR); and smartphones. All these technologies are evolving and blending. The technologies are integrated functionally because they underlie the Cybercare network, and/or form part of the care for patients using that distributed network. Moving health care provision to a networked, distributed model will save money, improve outcomes, facilitate access, improve security, increase patient and provider satisfaction, and may mitigate the international global burden of disease. In this paper we discuss how Cybercare is being implemented now, and envision its growth by 2030.",2016 May 27,"['Rosen, Joseph M.', 'Kun, Luis', 'Mosher, Robyn E.', 'Grigg, Elliott', 'Merrell, Ronald C.', 'Macedonia, Christian', 'Klaudt-Moreau, Julien', 'Price-Smith, Andrew', 'Geiling, James']",Health Technol (Berl),,,True
3660a0a14f82558378797b8a86fb7d0854bd1ab4,PMC,Porcine epidemic diarrhea virus (PEDV) detection and antibody response in commercial growing pigs,http://dx.doi.org/10.1186/s12917-016-0725-5,PMC4902975,27287624,CC BY,"BACKGROUND: Longitudinal samples from two production sites were used to (1) describe the pattern of PEDV shedding (rRT-PCR) in individual rectal swabs, pen fecal samples, and pen oral fluids (OF); (2) describe the kinetics of PEDV antibody by ELISA (IgA, IgG) testing of pig serum and pen oral fluid samples; and (3) establish cutoffs and performance estimates for PEDV WV ELISAs (IgA, IgG). Site One was PEDV positive; Site Two was PEDV negative. On Site One, pen samples (feces and oral fluids) and pig samples (rectal swabs and sera) were collected both before and after the population was exposed to PEDV. RESULTS: On Site Two, pen oral fluid samples and individual pig serum samples were negative for both PEDV antibody and nucleic acid. On Site One, PEDV was detected by rRT-PCR at 6 days post exposure (DPE) in all sample types. The last rRT-PCR positives were detected in rectal swabs and oral fluids on 69 DPE. IgG and IgA were detected in oral fluids and serum samples by 13 DPE. Analysis of the PEDV serum IgG WV ELISA data showed that a sample-to-positive (S/P) cutoff of ≥ 0.80 provided a diagnostic sensitivity of 0.87 (95 % CI: 0.82, 0.91) and specificity of 0.99 (95 % CI: 0.98, 1.00). Serum IgG results declined slowly over the monitoring period, with 60 % of serum samples positive (S/P ≥ 0.80) at the final sampling on 111 DPE. Analysis of the PEDV oral fluid IgA WV ELISA found that a cutoff of S/P ≥ 0.80 provided a diagnostic sensitivity of 1.00 (95 % CI: 0.92, 1.00) and a diagnostic specificity of 1.00 (95 % CI: 0.99, 1.00). The oral fluid IgA response increased through 96 DPE and began to decline at the last sampling on 111 DPE. CONCLUSIONS: This study showed that oral fluid-based testing could provide an easy and “animal-friendly” approach to sample collection for nucleic acid and/or antibody-based surveillance of PEDV in swine populations.",2016 Jun 10,"['Bjustrom-Kraft, Jordan', 'Woodard, Katie', 'Giménez-Lirola, Luis', 'Rotolo, Marisa', 'Wang, Chong', 'Sun, Yaxuan', 'Lasley, Peter', 'Zhang, Jianqiang', 'Baum, David', 'Gauger, Phillip', 'Main, Rodger', 'Zimmerman, Jeffrey']",BMC Vet Res,,,True
bca9f4ffe445882f2de559b938d83a69e90d2224,PMC,Etiologic Framework for the Study of Neurodegenerative Disorders as Well as Vascular and Metabolic Comorbidities on the Grounds of Shared Epidemiologic and Biologic Features,http://dx.doi.org/10.3389/fnagi.2016.00138,PMC4904010,27378910,CC BY,"Background: During the last two decades, protein aggregation at all organismal levels, from viruses to humans, has emerged from a neglected area of protein science to become a central issue in biology and biomedicine. This article constitutes a risk-based review aimed at supporting an etiologic scenario of selected, sporadic, protein-associated, i.e., conformational, neurodegenerative disorders (NDDs), and their vascular- and metabolic-associated ailments. Methods: A rationale is adopted, to incorporate selected clinical data and results from animal-model research, complementing epidemiologic evidences reported in two prior articles. Findings: Theory is formulated assuming an underlying conformational transmission mechanism, mediated either by horizontal transfer of mammalian genes coding for specific aggregation-prone proteins, or by xeno-templating between bacterial and host proteins. We build a few population-based and experimentally-testable hypotheses focusing on: (1) non-disposable surgical instruments for sporadic Creutzfeldt-Jakob disease (sCJD) and other rapid progressive neurodegenerative dementia (sRPNDd), multiple system atrophy (MSA), and motor neuron disease (MND); and (2) specific bacterial infections such as B. pertussis and E. coli for all forms, but particularly for late-life sporadic conformational, NDDs, type 2 diabetes mellitus (T2DM), and atherosclerosis where natural protein fibrils present in such organisms as a result of adaptation to the human host induce prion-like mechanisms. Conclusion: Implications for cohort alignment and experimental animal research are discussed and research lines proposed.",2016 Jun 13,"['de Pedro-Cuesta, Jesús', 'Martínez-Martín, Pablo', 'Rábano, Alberto', 'Ruiz-Tovar, María', 'Alcalde-Cabero, Enrique', 'Calero, Miguel']",Front Aging Neurosci,,,True
a8fb2e52e4545f4de90bc13e44ae914d9da6a8ab,PMC,Patient Isolation Precautions: Are They Worth It?,http://dx.doi.org/10.1155/2016/5352625,PMC4904523,27445547,CC BY,"Isolation precautions are intended to minimize pathogen transmission and reduce hospital-acquired infections. More recently, the effectiveness of isolation precautions has been questioned because of increasing evidence of risks. These putative downsides are divided into a quantifiable monetary cost (i.e., a literal cost to the system) and clinically important but less easily quantifiable costs (i.e., “costs” to the patient). The authors also briefly review deisolation and alternatives to isolation. The present review is not arguing against appropriate isolation or precautions, simply that the authors consider both risks and benefits and disseminate up-to-date information. Their patient-focused goal is to mitigate risks for those who truly need isolating and to end isolation as soon as it is safe and appropriate to do so.",2016 Apr 12,"['Sprague, Elliott', 'Reynolds, Steven', 'Brindley, Peter']",Can Respir J,,,True
fd4f419edc4e7a9ee255ea3bdc5b458a86ae4ab3,PMC,Bovine coronavirus in naturally and experimentally exposed calves; viral shedding and the potential for transmission,http://dx.doi.org/10.1186/s12985-016-0555-x,PMC4906604,27296861,CC BY,"BACKGROUND: Bovine coronavirus (BCoV) is a widely distributed pathogen, causing disease and economic losses in the cattle industry worldwide. Prevention of virus spread is impeded by a lack of basic knowledge concerning viral shedding and transmission potential in individual animals. The aims of the study were to investigate the duration and quantity of BCoV shedding in feces and nasal secretions related to clinical signs, the presence of virus in blood and tissues and to test the hypothesis that seropositive calves are not infectious to naïve in-contact calves three weeks after BCoV infection. METHODS: A live animal experiment was conducted, with direct contact between animal groups for 24 h as challenge procedure. Four naïve calves were commingled with a group of six naturally infected calves and sequentially euthanized. Two naïve sentinel calves were commingled with the experimentally exposed group three weeks after exposure. Nasal swabs, feces, blood and tissue samples were analyzed for viral RNA by RT-qPCR, and virus isolation was performed on nasal swabs. Serum was analyzed for BCoV antibodies. RESULTS: The calves showed mild general signs, and the most prominent signs were from the respiratory system. The overall clinical score corresponded well with the shedding of viral RNA the first three weeks after challenge. General depression and cough were the signs that correlated best with shedding of BCoV RNA, while peak respiratory rate and peak rectal temperature appeared more than a week later than the peak shedding. Nasal shedding preceded fecal shedding, and the calves had detectable amounts of viral RNA intermittently in feces through day 35 and in nasal secretions through day 28, however virus isolation was unsuccessful from day six and day 18 from the two calves investigated. Viral RNA was not detected in blood, but was found in lymphatic tissue through day 42 after challenge. Although the calves were shedding BCoV RNA 21 days after infection the sentinel animals were not infected. CONCLUSIONS: Prolonged shedding of BCoV RNA can occur, but detection of viral RNA does not necessarily indicate a transmission potential. The study provides valuable information with regard to producing scientifically based biosecurity advices. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0555-x) contains supplementary material, which is available to authorized users.",2016 Jun 13,"['Oma, Veslemøy Sunniva', 'Tråvén, Madeleine', 'Alenius, Stefan', 'Myrmel, Mette', 'Stokstad, Maria']",Virol J,,,True
e784769ed85685121bda82e89183d0b756686281,PMC,The Impact of Farmers’ Strategic Behavior on the Spread of Animal Infectious Diseases,http://dx.doi.org/10.1371/journal.pone.0157450,PMC4907430,27300368,CC BY,"One of the main strategies to control the spread of infectious animal diseases is the implementation of movement restrictions. This paper shows a loss in efficiency of the movement restriction policy (MRP) when behavioral responses of farmers are taken into account. Incorporating the strategic behavior of farmers in an epidemiologic model reveals that the MRP can trigger premature animal sales by farms at high risk of becoming infected that significantly reduce the efficacy of the policy. The results are validated in a parameterized network via Monte Carlo simulations and measures to mitigate the loss of efficiency of the MRP are discussed. Financial aid to farmers can be justified by public health concerns, not only for equity. This paper contributes to developing an interdisciplinary analytical framework regarding the expansion of infectious diseases combining economic and epidemiologic dimensions.",2016 Jun 14,"['Tago, Damian', 'Hammitt, James K.', 'Thomas, Alban', 'Raboisson, Didier']",PLoS One,,,True
52bf83ff771d92f697a4ab0cfe70a99503940050,PMC,Central Role of Ubiquitination in Genome Maintenance: DNA Replication and Damage Repair,http://dx.doi.org/10.5402/2012/146748,PMC4908256,27398234,CC BY,"Faithful transmission of genetic information through generations ensures genomic stability and integrity. However, genetic alterations occur every now and then during the course of genome duplication. In order to repair these genetic defects and lesions, nature has devised several repair pathways which function promptly to prevent the cell from accumulating permanent mutations. These repair mechanisms seem to be significantly impacted by posttranslational modifications of proteins like phosphorylation and ubiquitination. Protein ubiquitination is emerging as a critical regulatory mechanism of DNA damage response. Non-proteolytic, proteasome-independent functions of ubiquitin involving monoubiquitination and polyubiquitination of DNA repair proteins contribute significantly to the signaling of DNA repair pathways. In this paper, we will particularly highlight the work on ubiquitin-mediated signaling in the repair processes involving the Fanconi anemia pathway, translesional synthesis, nucleotide excision repair, and repair of double-strand breaks. We will also discuss the role of ubiquitin ligases in regulating checkpoint mechanisms, the role of deubiquitinating enzymes, and the growing possibilities of therapeutic intervention in this ubiquitin-conjugation system.",2012 Feb 8,"['Ghosh, Soma', 'Saha, Tapas']",ISRN Mol Biol,,,True
b061aea11013896c5d3a9c7c0c4f884397ad38d9,PMC,Animal Models of Cystic Fibrosis Pathology: Phenotypic Parallels and Divergences,http://dx.doi.org/10.1155/2016/5258727,PMC4908263,27340661,CC BY,"Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The resultant characteristic ion transport defect results in decreased mucociliary clearance, bacterial colonisation, and chronic neutrophil-dominated inflammation. Much knowledge surrounding the pathophysiology of the disease has been gained through the generation of animal models, despite inherent limitations in each. The failure of certain mouse models to recapitulate the phenotypic manifestations of human disease has initiated the generation of larger animals in which to study CF, including the pig and the ferret. This review will summarise the basic phenotypes of three animal models and describe the contributions of such animal studies to our current understanding of CF.",2016 Jun 1,"['Lavelle, Gillian M.', 'White, Michelle M.', 'Browne, Niall', 'McElvaney, Noel G.', 'Reeves, Emer P.']",Biomed Res Int,,,True
47d93c4d0e435b2da5ebc11b4404ed209447f5a0,PMC,Angiotensin-converting enzyme 2 prevents lipopolysaccharide-induced rat acute lung injury via suppressing the ERK1/2 and NF-κB signaling pathways,http://dx.doi.org/10.1038/srep27911,PMC4908402,27302421,CC BY,"Acute respiratory distress syndrome (ARDS) caused by severe sepsis remains a major challenge in intensive care medicine. ACE2 has been shown to protect against lung injury. However, the mechanisms of its protective effects on ARDS are largely unknown. Here, we report that ACE2 prevents LPS-induced ARDS by inhibiting MAPKs and NF-κB signaling pathway. Lentiviral packaged Ace2 cDNA or Ace2 shRNA was intratracheally administrated into the lungs of male SD rats. Two weeks after gene transfer, animals received LPS (7.5 mg/Kg) injection alone or in combination with Mas receptor antagonist A779 (10 μg/Kg) or ACE2 inhibitor MLN-4760 (1 mg/Kg) pretreatment. LPS-induced lung injury and inflammatory response were significantly prevented by ACE2 overexpression and deteriorated by Ace2 shRNA. A779 or MLN-4760 pretreatment abolished the protective effects of ACE2. Moreover, overexpression of ACE2 significantly reduced the Ang II/Ang-(1-7) ratio in BALF and up-regulated Mas mRNA expression in lung, which was reversed by A779. Importantly, the blockade of ACE2 on LPS-induced phosphorylation of ERK1/2, p38 and p50/p65 was also abolished by A779. Whereas, only the ERK1/2 inhibitor significantly attenuated lung injury in ACE2 overexpressing rats pretreated with A779. Our observation suggests that AEC2 attenuates LPS-induced ARDS via the Ang-(1-7)/Mas pathway by inhibiting ERK/NF-κB activation.",2016 Jun 15,"['Li, Yingchuan', 'Zeng, Zhen', 'Cao, Yongmei', 'Liu, Yujing', 'Ping, Feng', 'Liang, Mengfan', 'Xue, Ying', 'Xi, Caihua', 'Zhou, Ming', 'Jiang, Wei']",Sci Rep,,,True
0bdae8c38f570965cc9a630a44b7089c2a5da0ed,PMC,Involvement of miR-15a in G0/G1 Phase Cell Cycle Arrest Induced by Porcine Circovirus Type 2 Replication,http://dx.doi.org/10.1038/srep27917,PMC4908419,27302568,CC BY,"Many viruses exploit the host cell division cycle to favour their own growth. Here we demonstrated that porcine circovirus type 2 (PCV2), which is a major causative agent of an emerging and important swine disease complex, PCV2-associated diseases, caused G0/G1 cell cycle arrest through degradation of cyclin D1 and E followed by reduction of retinoblastoma phosphorylation in synchronized PCV2-infected cells dependent upon virus replication. This induction of G0/G1 cell cycle arrest promoted PCV2 replication as evidenced by increased viral protein expression and progeny virus production in the synchronized PCV2-infected cells. To delineate a mechanism of miRNAs in regulating PCV2-induced G0/G1 cell cycle arrest, we determined expression levels of some relevant miRNAs and found that only miR-15a but not miR-16, miR-21, and miR-34a was significantly changed in the PCV2-infected cells. We further demonstrated that upregulation of miR-15a promoted PCV2-induced G0/G1 cell cycle arrest via mediating cyclins D1 and E degradation, in which involves PCV2 growth. These results reveal that G0/G1 cell cycle arrest induced by PCV2 may provide favourable conditions for viral protein expression and progeny production and that miR-15a is implicated in PCV2-induced cell cycle control, thereby contributing to efficient viral replication.",2016 Jun 15,"['Quan, Rong', 'Wei, Li', 'Zhu, Shanshan', 'Wang, Jing', 'Cao, Yongchang', 'Xue, Chunyi', 'Yan, Xu', 'Liu, Jue']",Sci Rep,,,True
06525dbe27937be0f8263a0e8ec743f68d9f1795,PMC,Challenges with using names to link digital biodiversity information,http://dx.doi.org/10.3897/BDJ.4.e8080,PMC4910497,27346955,CC BY,,2016 May 25,"['Patterson, David', 'Mozzherin, Dmitry', 'Shorthouse, David Peter', 'Thessen, Anne']",Biodivers Data J,,,True
7cedb2a5addb854f9c6e833c54e6a352c55a442e,PMC,Fatal canine distemper virus infection of giant pandas in China,http://dx.doi.org/10.1038/srep27518,PMC4910525,27310722,CC BY,"We report an outbreak of canine distemper virus (CDV) infection among endangered giant pandas (Ailuropoda melanoleuca). Five of six CDV infected giant pandas died. The surviving giant panda was previously vaccinated against CDV. Genomic sequencing of CDV isolated from one of the infected pandas (giant panda/SX/2014) suggests it belongs to the Asia-1 cluster. The hemagglutinin protein of the isolated virus and virus sequenced from lung samples originating from deceased giant pandas all possessed the substitutions V26M, T213A, K281R, S300N, P340Q, and Y549H. The presence of the Y549H substitution is notable as it is found at the signaling lymphocytic activation molecule (SLAM) receptor-binding site and has been implicated in the emergence of highly pathogenic CDV and host switching. These findings demonstrate that giant pandas are susceptible to CDV and suggest that surveillance and vaccination among all captive giant pandas are warranted to support conservation efforts for this endangered species.",2016 Jun 16,"['Feng, Na', 'Yu, Yicong', 'Wang, Tiecheng', 'Wilker, Peter', 'Wang, Jianzhong', 'Li, Yuanguo', 'Sun, Zhe', 'Gao, Yuwei', 'Xia, Xianzhu']",Sci Rep,,,True
1385574de3fa0e19e17a0bea94bedebd9c6456e5,PMC,Fatal canine distemper virus infection of giant pandas in China,http://dx.doi.org/10.1038/srep27518,PMC4910525,27310722,CC BY,"We report an outbreak of canine distemper virus (CDV) infection among endangered giant pandas (Ailuropoda melanoleuca). Five of six CDV infected giant pandas died. The surviving giant panda was previously vaccinated against CDV. Genomic sequencing of CDV isolated from one of the infected pandas (giant panda/SX/2014) suggests it belongs to the Asia-1 cluster. The hemagglutinin protein of the isolated virus and virus sequenced from lung samples originating from deceased giant pandas all possessed the substitutions V26M, T213A, K281R, S300N, P340Q, and Y549H. The presence of the Y549H substitution is notable as it is found at the signaling lymphocytic activation molecule (SLAM) receptor-binding site and has been implicated in the emergence of highly pathogenic CDV and host switching. These findings demonstrate that giant pandas are susceptible to CDV and suggest that surveillance and vaccination among all captive giant pandas are warranted to support conservation efforts for this endangered species.",2016 Jun 16,"['Feng, Na', 'Yu, Yicong', 'Wang, Tiecheng', 'Wilker, Peter', 'Wang, Jianzhong', 'Li, Yuanguo', 'Sun, Zhe', 'Gao, Yuwei', 'Xia, Xianzhu']",Sci Rep,,,False
d3c04715d99a379da9cf526b7542f027cf0a04c6,PMC,Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study,http://dx.doi.org/10.1371/journal.pone.0157398,PMC4911076,27309354,CC BY,"OBJECTIVE: Febrile neutropenia is common in children undergoing chemotherapy for the treatment of malignancies. In the majority of cases, the cause of the fever is unknown. Although respiratory viruses are commonly associated with this condition, the etiologic significance of this finding remains unclear and is therefore the subject of this study. STUDY DESIGN: Nasopharyngeal aspirates were collected during 87 episodes of febrile neutropenia in children age 0–18 years, being treated at a children’s oncology unit between January 2013 and June 2014. Real-time polymerase chain reaction was used to determine the presence of 16 respiratory viruses. Follow-up samples were collected from children who tested positive for one or more respiratory viruses. Rhinoviruses were genotyped by VP4/VP2 sequencing. Fisher’s exact test and Mann-Whitney U test were used for group comparisons. RESULTS: At least one respiratory virus was detected in samples from 39 of 87 episodes of febrile neutropenia (45%), with rhinoviruses the most frequently detected. Follow-up samples were collected after a median of 28 days (range, 9–74 days) in 32 of the 39 virus-positive episodes. The respiratory viral infection had resolved in 25 episodes (78%). The same virus was detected at follow-up in one coronavirus and six rhinovirus episodes. Genotyping revealed a different rhinovirus species in two of the six rhinovirus infections. CONCLUSION: The frequency of respiratory viral infections in this group of patients suggests an etiologic role in febrile neutropenia. However, these findings must be confirmed in larger patient cohorts.",2016 Jun 16,"['Söderman, Martina', 'Rhedin, Samuel', 'Tolfvenstam, Thomas', 'Rotzén-Östlund, Maria', 'Albert, Jan', 'Broliden, Kristina', 'Lindblom, Anna']",PLoS One,,,True
a0444a2148ffe99348088aa7c04e21dcea70d602,PMC,Remyelination Is Correlated with Regulatory T Cell Induction Following Human Embryoid Body-Derived Neural Precursor Cell Transplantation in a Viral Model of Multiple Sclerosis,http://dx.doi.org/10.1371/journal.pone.0157620,PMC4911106,27310015,CC BY,"We have recently described sustained clinical recovery associated with dampened neuroinflammation and remyelination following transplantation of neural precursor cells (NPCs) derived from human embryonic stem cells (hESCs) in a viral model of the human demyelinating disease multiple sclerosis. The hNPCs used in that study were derived by a novel direct differentiation method (direct differentiation, DD-NPCs) that resulted in a unique gene expression pattern when compared to hNPCs derived by conventional methods. Since the therapeutic potential of human NPCs may differ greatly depending on the method of derivation and culture, we wanted to determine whether NPCs differentiated using conventional methods would be similarly effective in improving clinical outcome under neuroinflammatory demyelinating conditions. For the current study, we utilized hNPCs differentiated from a human induced pluripotent cell line via an embryoid body intermediate stage (EB-NPCs). Intraspinal transplantation of EB-NPCs into mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) resulted in decreased accumulation of CD4+ T cells in the central nervous system that was concomitant with reduced demyelination at the site of injection. Dampened neuroinflammation and remyelination was correlated with a transient increase in CD4+FOXP3+ regulatory T cells (Tregs) concentrated within the peripheral lymphatics. However, compared to our earlier study, pathological improvements were modest and did not result in significant clinical recovery. We conclude that the genetic signature of NPCs is critical to their effectiveness in this model of viral-induced neurologic disease. These comparisons will be useful for understanding what factors are critical for the sustained clinical improvement.",2016 Jun 16,"['Plaisted, Warren C.', 'Zavala, Angel', 'Hingco, Edna', 'Tran, Ha', 'Coleman, Ronald', 'Lane, Thomas E.', 'Loring, Jeanne F.', 'Walsh, Craig M.']",PLoS One,,,True
4cfaea8e65d7e5f6884cffa4055f7f0b48ca164c,PMC,Induction of Apoptosis by the Nonstructural Protein 4 and 10 of Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1371/journal.pone.0156518,PMC4911139,27310256,CC BY,"Infection by most viruses triggers apoptosis in host cells, and viruses manipulate this cell response to promote viral replication, virus spread, and cell killing. Porcine reproductive and respiratory syndrome virus (PRRSV) has been shown to induce apoptosis both in vitro and in vivo, while the regulatory roles of PRRSV-encoded products in apoptosis are not fully understood. In the present study, we first showed a biphasic apoptosis regulation by a highly pathogenic PRRSV strain JXwn06. It was indicated that PRRSV infection delays apoptosis at early infection but activates apoptosis at late infection in MARC-145 cells. In PRRSV-infected MARC-145 cells, procaspase-8, -9 and -12 were activated at late infection, demonstrating the involvements of death receptor pathway, mitochondrial pathway and endoplasmic reticulum (ER) stress pathway in inducing apoptosis. PRRSV was also shown to induce a similar apoptosis process in pulmonary alveolar macrophages (PAMs) with an early initiation. Next, the PRRSV-encoded apoptosis inducers were screened, indicating that the nonstructural protein (Nsp) 4 and Nsp10 of PRRSV are pro-apoptotic. In the presence of Nsp4, it was confirmed that procaspase-8, -9 and -12 were cleaved, and Nsp4 facilitates the cleavage of procaspase-9 by activating B-cell lymphoma 2 interacting mediator of cell death (Bim), a pro-apoptotic protein. In addition, Nsp4 was shown to induce the degradation of an anti-apoptotic protein, B-cell lymphoma-extra large (Bcl-xL). Nsp10 was shown to activate procaspase-8 and -9 but procaspase-12 and to upregulate the expression of BH3-only pro-apoptotic protein BH3 interacting-domain death agonist (Bid) and its active form, truncated Bid (tBid). Clearly, the participation of both activated caspase-8 and Bid is required for Nsp10-induced apoptosis, indicating a crosstalk between extrinsic- and mitochondria-dependent pathways. Together, our findings suggest that PRRSV infection regulates apoptosis in a two-phase manner and activates all three apoptotic pathways; the Nsp4 and Nsp10 of PRRSV function as apoptosis inducers with different molecular basis.",2016 Jun 16,"['Yuan, Shuaizhen', 'Zhang, Ning', 'Xu, Lei', 'Zhou, Lei', 'Ge, Xinna', 'Guo, Xin', 'Yang, Hanchun']",PLoS One,,,True
f0cbe63a26a901e5873aefd4c01faaa078c89c81,PMC,Induction of Apoptosis by the Nonstructural Protein 4 and 10 of Porcine Reproductive and Respiratory Syndrome Virus,http://dx.doi.org/10.1371/journal.pone.0156518,PMC4911139,27310256,CC BY,"Infection by most viruses triggers apoptosis in host cells, and viruses manipulate this cell response to promote viral replication, virus spread, and cell killing. Porcine reproductive and respiratory syndrome virus (PRRSV) has been shown to induce apoptosis both in vitro and in vivo, while the regulatory roles of PRRSV-encoded products in apoptosis are not fully understood. In the present study, we first showed a biphasic apoptosis regulation by a highly pathogenic PRRSV strain JXwn06. It was indicated that PRRSV infection delays apoptosis at early infection but activates apoptosis at late infection in MARC-145 cells. In PRRSV-infected MARC-145 cells, procaspase-8, -9 and -12 were activated at late infection, demonstrating the involvements of death receptor pathway, mitochondrial pathway and endoplasmic reticulum (ER) stress pathway in inducing apoptosis. PRRSV was also shown to induce a similar apoptosis process in pulmonary alveolar macrophages (PAMs) with an early initiation. Next, the PRRSV-encoded apoptosis inducers were screened, indicating that the nonstructural protein (Nsp) 4 and Nsp10 of PRRSV are pro-apoptotic. In the presence of Nsp4, it was confirmed that procaspase-8, -9 and -12 were cleaved, and Nsp4 facilitates the cleavage of procaspase-9 by activating B-cell lymphoma 2 interacting mediator of cell death (Bim), a pro-apoptotic protein. In addition, Nsp4 was shown to induce the degradation of an anti-apoptotic protein, B-cell lymphoma-extra large (Bcl-xL). Nsp10 was shown to activate procaspase-8 and -9 but procaspase-12 and to upregulate the expression of BH3-only pro-apoptotic protein BH3 interacting-domain death agonist (Bid) and its active form, truncated Bid (tBid). Clearly, the participation of both activated caspase-8 and Bid is required for Nsp10-induced apoptosis, indicating a crosstalk between extrinsic- and mitochondria-dependent pathways. Together, our findings suggest that PRRSV infection regulates apoptosis in a two-phase manner and activates all three apoptotic pathways; the Nsp4 and Nsp10 of PRRSV function as apoptosis inducers with different molecular basis.",2016 Jun 16,"['Yuan, Shuaizhen', 'Zhang, Ning', 'Xu, Lei', 'Zhou, Lei', 'Ge, Xinna', 'Guo, Xin', 'Yang, Hanchun']",PLoS One,,,False
3fa2c03259615e7a062deaac928c626c0a1bfbf7,PMC,Pharmacologic Inhibition of Host Phosphodiesterase-4 Improves Isoniazid-Mediated Clearance of Mycobacterium tuberculosis,http://dx.doi.org/10.3389/fimmu.2016.00238,PMC4911353,27379099,CC BY,"The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment. Previously, we showed that the administration of CC-3052, a phosphodiesterase-4 inhibitor (PDE4i), reduced the host inflammatory response during Mycobacterium tuberculosis (Mtb) infection and improved the antimicrobial efficacy of isoniazid (INH) in both the mouse and rabbit models. In the present study, we evaluated the pharmacokinetics and explored the mechanism underlying the efficacy of a more potent PDE4i, CC-11050, as adjunct to INH treatment in a mouse model of pulmonary Mtb infection. Genome-wide lung transcriptome analysis confirmed the dampening of inflammation and associated network genes that we previously reported with CC-3052. Consistent with the reduction in inflammation, a significant improvement in Mtb control and pathology was observed in the lungs of mice treated with CC-11050 plus INH, compared to INH alone. This important confirmatory study will be used to help design upcoming human clinical trials with CC-11050 as an HDT for TB treatment.",2016 Jun 17,"['Subbian, Selvakumar', 'Koo, Mi-Sun', 'Tsenova, Liana', 'Khetani, Vikram', 'Zeldis, Jerome B.', 'Fallows, Dorothy', 'Kaplan, Gilla']",Front Immunol,,,True
50adcf9bfee16b95201df9fdcc9dcf30c1f8ea6e,PMC,In Vitro and In Vivo Attenuation of Vesicular Stomatitis Virus (VSV) by Phosphoprotein Deletion,http://dx.doi.org/10.1371/journal.pone.0157287,PMC4912100,27315286,CC BY,"Vesicular stomatitis virus (VSV) is highly immunogenic and able to stimulate both innate and adaptive immune responses. However, its ability to induce adverse effects has held back the use of VSV as a potential vaccine vector. In this study we developed VSV-ΔP, a safe yet potent replication-defective recombinant VSV in which the phosphoprotein (P) gene was deleted. VSV-ΔP replicated only in supporting cells expressing P (BHK-P cells) and at levels more than 2 logs lower than VSV. In vivo studies indicated that the moderate replication of VSV-ΔP in vitro was associated with the attenuation of this virus in the mouse model, whereas mice intracranially injected with VSV succumbed to neurotoxicity. Furthermore, we constructed VSV and VSV-ΔP expressing a variety of antigens including hemagglutinin-neuraminidase (HN) from Newcastle disease virus (NDV), hemagglutinin (HA) from either a 2009 H1N1 pandemic influenza virus (pdm/09) or the avian H7N9. VSV and VSV-ΔP incorporated the foreign antigens on their surface resulting in induction of robust neutralizing antibody, serum IgG, and hemagglutination inhibition (HAI) titers against their corresponding viruses. These results indicated that VSV with P gene deletion was attenuated in vitro and in vivo, and possibly expressed the foreign antigen on its surface. Therefore, the P gene-deletion strategy may offer a potentially useful and safer approach for attenuating negative-sense RNA viruses which use phosphoprotein as a cofactor for viral replication.",2016 Jun 17,"['Wongthida, Phonphimon', 'Jengarn, Juggragarn', 'Narkpuk, Jaraspim', 'Koonyosying, Pongpisid', 'Srisutthisamphan, Kanjana', 'Wanitchang, Asawin', 'Leaungwutiwong, Pornsawan', 'Teeravechyan, Samaporn', 'Jongkaewwattana, Anan']",PLoS One,,,True
ec317e9df67d2d7fba6904163bd6f69a79380d73,PMC,Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF),http://dx.doi.org/10.1371/journal.pone.0157034,PMC4912142,27314851,CC BY,"Necrotizing enterocolitis (NEC) is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues. This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues. Epidermal growth factor (EGF), typically found in bodily fluids, such as amniotic fluid, salvia and mother’s breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants. We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF. Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N’ terminal were produced. Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed. Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein. Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform.",2016 Jun 17,"['He, Yonghua', 'Schmidt, Monica A.', 'Erwin, Christopher', 'Guo, Jun', 'Sun, Raphael', 'Pendarvis, Ken', 'Warner, Brad W.', 'Herman, Eliot M.']",PLoS One,,,True
6f66ba164fba7cd9449ae02d511e2ae8c32b53e4,PMC,High detection rate of dog circovirus in diarrheal dogs,http://dx.doi.org/10.1186/s12917-016-0722-8,PMC4912760,27315792,CC BY,"BACKGROUND: Diarrhea is one of the most common clinical symptoms reported in companion animal clinics. Dog circovirus (DogCV) is a new mammalian circovirus that is considered to be a cause of alimentary syndromes such as diarrhea, vomiting and hemorrhagic enteritis. DogCV has previously only been identified in the United States, Italy, Germany (GeneBank accession number: KF887949) and China (GeneBank accession number: KT946839). Therefore, the aims of this study were to determine the prevalence of DogCV in Taiwan and to explore the correlation between diarrhea and DogCV infection. Clinical specimens were collected between 2012 and 2014 from 207 dogs suffering from diarrhea and 160 healthy dogs. RESULTS: In this study, we developed a sensitive and specific SYBR Green-based real-time PCR assays to detected DogCV in naturally infected animals. Of the analyzed fecal samples from diarrheal dogs and health dogs, 58 (28.0 %) and 19 (11.9 %), respectively, were DogCV positive. The difference in DogCV prevalence was highly significant (P = 0.0002755) in diarrheal dogs. CONCLUSIONS: This is the first study to reveal that DogCV is currently circulating in domestic dogs in Taiwan and to demonstrate its high detection rate in dogs with diarrhea. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0722-8) contains supplementary material, which is available to authorized users.",2016 Jun 17,"['Hsu, Han-Siang', 'Lin, Ting-Han', 'Wu, Hung-Yi', 'Lin, Lee-Shuan', 'Chung, Cheng-Shu', 'Chiou, Ming-Tang', 'Lin, Chao-Nan']",BMC Vet Res,,,True
cdc7a84bccdf6a66bb0e2c902a818aa09ffabfc9,PMC,Tanreqing Injection Attenuates Lipopolysaccharide-Induced Airway Inflammation through MAPK/NF-κB Signaling Pathways in Rats Model,http://dx.doi.org/10.1155/2016/5292346,PMC4913016,27366191,CC BY,"Background. Tanreqing injection (TRQ) is a commonly used herbal patent medicine for treating inflammatory airway diseases in view of its outstanding anti-inflammatory properties. In this study, we explored the signaling pathways involved in contributions of TRQ to LPS-induced airway inflammation in rats. Methods/Design. Adult male Sprague Dawley (SD) rats randomly divided into different groups received intratracheal instillation of LPS and/or intraperitoneal injection of TRQ. Bronchoalveolar Lavage Fluid (BALF) and lung samples were collected at 24 h, 48 h, and 96 h after TRQ administration. Protein and mRNA levels of tumor necrosis factor- (TNF-) α, Interleukin- (IL-) 1β, IL-6, and IL-8 in BALF and lung homogenate were observed by ELISA and real-time PCR, respectively. Lung sections were stained for p38 MAPK and NF-κB detection by immunohistochemistry. Phospho-p38 MAPK, phosphor-extracellular signal-regulated kinases ERK1/2, phospho-SAPK/JNK, phospho-NF-κB p65, phospho-IKKα/β, and phospho-IκB-α were measured by western blot analysis. Results. The results showed that TRQ significantly counteracted LPS-stimulated release of TNF-α, IL-1β, IL-6, and IL-8, attenuated cells influx in BALF, mitigated mucus hypersecretion, suppressed phosphorylation of NF-κB p65, IκB-α, ΙKKα/β, ERK1/2, JNK, and p38 MAPK, and inhibited p38 MAPK and NF-κB p65 expression in rat lungs. Conclusions. Results of the current research indicate that TRQ possesses potent exhibitory effects in LPS-induced airway inflammation by, at least partially, suppressing the MAPKs and NF-κB signaling pathways, in a general dose-dependent manner.",2016 Jun 5,"['Liu, Wei', 'Jiang, Hong-li', 'Cai, Lin-li', 'Yan, Min', 'Dong, Shou-jin', 'Mao, Bing']",Evid Based Complement Alternat Med,,,True
ebbe2e390320b9cd9399ba2e7d011df6e953971e,PMC,The epidermal growth factor receptor regulates cofilin activity and promotes transmissible gastroenteritis virus entry into intestinal epithelial cells,http://dx.doi.org/10.18632/oncotarget.7723,PMC4914279,26933809,CC BY,"Transmissible gastroenteritis virus (TGEV), a coronavirus, causes severe diarrhea and high mortality in newborn piglets. The porcine intestinal epithelium is the target of TGEV infection, but the mechanisms that TGEV disrupts the actin cytoskeleton and invades the host epithelium remain largely unknown. We not only found that TGEV infection stimulates F-actin to gather at the cell membrane but the disruption of F-actin inhibits TGEV entry as well. Cofilin is involved in F-actin reorganization and TGEV entry. The TGEV spike protein is capable of binding with EGFR, activating the downstream phosphoinositide-3 kinase (PI3K), then causing the phosphorylation of cofilin and F-actin polymerization via Rac1/Cdc42 GTPases. Inhibition of EGFR and PI3K decreases the entry of TGEV. EGFR is also the upstream activator of mitogen-activated protein kinase (MAPK) signaling pathways that is involved in F-actin reorganization. Additionally, lipid rafts act as signal platforms for the EGFR-associated signaling cascade and correlate with the adhesion of TGEV. In conlusion, these results provide valuable data of the mechanisms which are responsible for the TGEV pathogenesis and may lead to the development of new methods about controlling TGEV.",2016 Feb 25,"['Hu, Weiwei', 'Zhu, Liqi', 'Yang, Xing', 'Lin, Jian', 'Yang, Qian']",Oncotarget,,,True
e5af126d541f65e20bf349843f191730486b0814,PMC,The epidermal growth factor receptor regulates cofilin activity and promotes transmissible gastroenteritis virus entry into intestinal epithelial cells,http://dx.doi.org/10.18632/oncotarget.7723,PMC4914279,26933809,CC BY,"Transmissible gastroenteritis virus (TGEV), a coronavirus, causes severe diarrhea and high mortality in newborn piglets. The porcine intestinal epithelium is the target of TGEV infection, but the mechanisms that TGEV disrupts the actin cytoskeleton and invades the host epithelium remain largely unknown. We not only found that TGEV infection stimulates F-actin to gather at the cell membrane but the disruption of F-actin inhibits TGEV entry as well. Cofilin is involved in F-actin reorganization and TGEV entry. The TGEV spike protein is capable of binding with EGFR, activating the downstream phosphoinositide-3 kinase (PI3K), then causing the phosphorylation of cofilin and F-actin polymerization via Rac1/Cdc42 GTPases. Inhibition of EGFR and PI3K decreases the entry of TGEV. EGFR is also the upstream activator of mitogen-activated protein kinase (MAPK) signaling pathways that is involved in F-actin reorganization. Additionally, lipid rafts act as signal platforms for the EGFR-associated signaling cascade and correlate with the adhesion of TGEV. In conlusion, these results provide valuable data of the mechanisms which are responsible for the TGEV pathogenesis and may lead to the development of new methods about controlling TGEV.",2016 Feb 25,"['Hu, Weiwei', 'Zhu, Liqi', 'Yang, Xing', 'Lin, Jian', 'Yang, Qian']",Oncotarget,,,False
063ac3f62e4657ad610a771fc796bba4f3e404b2,PMC,De Novo Assembly and Comparative Transcriptome Analysis Provide Insight into Lysine Biosynthesis in Toona sinensis Roem,http://dx.doi.org/10.1155/2016/6735209,PMC4914729,27376077,CC BY,"Toona sinensis Roem is a popular leafy vegetable in Chinese cuisine and is also used as a traditional Chinese medicine. In this study, leaf samples were collected from the same plant on two development stages and then used for high-throughput Illumina RNA-sequencing (RNA-Seq). 125,884 transcripts and 54,628 unigenes were obtained through de novo assembly. A total of 25,570 could be annotated with known biological functions, which indicated that the T. sinensis leaves and shoots were undergoing multiple developmental processes especially for active metabolic processes. Analysis of differentially expressed unigenes between the two libraries showed that the lysine biosynthesis was an enriched KEGG pathway, and candidate genes involved in the lysine biosynthesis pathway in T. sinensis leaves and shoots were identified. Our results provide a primary analysis of the gene expression files of T. sinensis leaf and shoot on different development stages and afford a valuable resource for genetic and genomic research on plant lysine biosynthesis.",2016 Jun 7,"['Zhang, Xia', 'Song, Zhenqiao', 'Liu, Tian', 'Guo, Linlin', 'Li, Xingfeng']",Int J Genomics,,,False
8e96ff3220b7201598d2c5099ff9a4d03e529b3b,PMC,De Novo Assembly and Comparative Transcriptome Analysis Provide Insight into Lysine Biosynthesis in Toona sinensis Roem,http://dx.doi.org/10.1155/2016/6735209,PMC4914729,27376077,CC BY,"Toona sinensis Roem is a popular leafy vegetable in Chinese cuisine and is also used as a traditional Chinese medicine. In this study, leaf samples were collected from the same plant on two development stages and then used for high-throughput Illumina RNA-sequencing (RNA-Seq). 125,884 transcripts and 54,628 unigenes were obtained through de novo assembly. A total of 25,570 could be annotated with known biological functions, which indicated that the T. sinensis leaves and shoots were undergoing multiple developmental processes especially for active metabolic processes. Analysis of differentially expressed unigenes between the two libraries showed that the lysine biosynthesis was an enriched KEGG pathway, and candidate genes involved in the lysine biosynthesis pathway in T. sinensis leaves and shoots were identified. Our results provide a primary analysis of the gene expression files of T. sinensis leaf and shoot on different development stages and afford a valuable resource for genetic and genomic research on plant lysine biosynthesis.",2016 Jun 7,"['Zhang, Xia', 'Song, Zhenqiao', 'Liu, Tian', 'Guo, Linlin', 'Li, Xingfeng']",Int J Genomics,,,True
c8d2fa6e178d17b218df59b33cfcb5839af7dc7f,PMC,No involvement of alveolar macrophages in the initiation of carbon nanoparticle induced acute lung inflammation in mice,http://dx.doi.org/10.1186/s12989-016-0144-6,PMC4915176,27328634,CC BY,"BACKGROUND: Carbonaceous nanoparticles (CNP) represent a major constituent of urban particulate air pollution, and inhalation of high CNP levels has been described to trigger a pro-inflammatory response of the lung. While several studies identified specific particle characteristics driving respiratory toxicity of low-solubility and low-toxicity particles such as CNP, the major lung cell type, which initiates and drives that response, remains still uncertain. Since alveolar macrophages (AM) are known to effectively phagocytose inhaled particles and play a crucial role for the initiation of pulmonary inflammation caused by invading microbes, we aimed to determine their role for sterile stimuli such as CNP by profiling the primary alveolar cell compartments of the lung. We exposed C57BL/6 mice to 20 μg CNP by intratracheal instillation and comprehensively investigated the expression of the underlying mediators during a time span of 3 to 72 h in three different lung cell populations: CD45- (negative) structural cells, CD45+ (positive) leukocytes, and by BAL recovered cells. RESULTS: Bronchoalveolar lavage (BAL) analysis revealed an acute inflammatory response characterized by the most prominent culmination of neutrophil granulocytes from 12 to 24 h after instillation, which declined to basal levels by day 7. As early as 3 h after CNP exposure 50 % of the AM revealed particle laden. BAL concentrations and lung gene expression profiles of TNFα, and the neutrophil chemoattractants CXCL1,-2 and-5 preceded the neutrophil recruitment and showed highest levels after 12 h of CNP exposure, pointing to a significant activation of the inflammation-evoking lung cells at this point of time. AM, isolated from lungs 3 to 12 h after CNP instillation, however, did not show a pro-inflammatory signature. On the contrary, gene expression analysis of different lung cell populations isolated 12 h after CNP instillation revealed CD45-, mainly representing alveolar epithelial type II (ATII) cells as major producer of inflammatory CXCL cytokines. Particularly by CD45- cells expressed Cxcl5 proved to be the most abundant chemokine, being 12 h after CNP exposure 24 (±11) fold induced. CONCLUSION: Our data suggests that AM are noninvolved in the initiation of the inflammatory response. ATII cells, which induced highest CXCL levels early on, might in contrast be the driver of acute neutrophilic inflammation upon pulmonary CNP exposure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-016-0144-6) contains supplementary material, which is available to authorized users.",2016 Jun 21,"['Chen, Shanze', 'Yin, Renfu', 'Mutze, Kathrin', 'Yu, Youjia', 'Takenaka, Shinji', 'Königshoff, Melanie', 'Stoeger, Tobias']",Part Fibre Toxicol,,,True
34c60b33c493dfe1545112d9f4b1107576f11dbd,PMC,No involvement of alveolar macrophages in the initiation of carbon nanoparticle induced acute lung inflammation in mice,http://dx.doi.org/10.1186/s12989-016-0144-6,PMC4915176,27328634,CC BY,"BACKGROUND: Carbonaceous nanoparticles (CNP) represent a major constituent of urban particulate air pollution, and inhalation of high CNP levels has been described to trigger a pro-inflammatory response of the lung. While several studies identified specific particle characteristics driving respiratory toxicity of low-solubility and low-toxicity particles such as CNP, the major lung cell type, which initiates and drives that response, remains still uncertain. Since alveolar macrophages (AM) are known to effectively phagocytose inhaled particles and play a crucial role for the initiation of pulmonary inflammation caused by invading microbes, we aimed to determine their role for sterile stimuli such as CNP by profiling the primary alveolar cell compartments of the lung. We exposed C57BL/6 mice to 20 μg CNP by intratracheal instillation and comprehensively investigated the expression of the underlying mediators during a time span of 3 to 72 h in three different lung cell populations: CD45- (negative) structural cells, CD45+ (positive) leukocytes, and by BAL recovered cells. RESULTS: Bronchoalveolar lavage (BAL) analysis revealed an acute inflammatory response characterized by the most prominent culmination of neutrophil granulocytes from 12 to 24 h after instillation, which declined to basal levels by day 7. As early as 3 h after CNP exposure 50 % of the AM revealed particle laden. BAL concentrations and lung gene expression profiles of TNFα, and the neutrophil chemoattractants CXCL1,-2 and-5 preceded the neutrophil recruitment and showed highest levels after 12 h of CNP exposure, pointing to a significant activation of the inflammation-evoking lung cells at this point of time. AM, isolated from lungs 3 to 12 h after CNP instillation, however, did not show a pro-inflammatory signature. On the contrary, gene expression analysis of different lung cell populations isolated 12 h after CNP instillation revealed CD45-, mainly representing alveolar epithelial type II (ATII) cells as major producer of inflammatory CXCL cytokines. Particularly by CD45- cells expressed Cxcl5 proved to be the most abundant chemokine, being 12 h after CNP exposure 24 (±11) fold induced. CONCLUSION: Our data suggests that AM are noninvolved in the initiation of the inflammatory response. ATII cells, which induced highest CXCL levels early on, might in contrast be the driver of acute neutrophilic inflammation upon pulmonary CNP exposure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-016-0144-6) contains supplementary material, which is available to authorized users.",2016 Jun 21,"['Chen, Shanze', 'Yin, Renfu', 'Mutze, Kathrin', 'Yu, Youjia', 'Takenaka, Shinji', 'Königshoff, Melanie', 'Stoeger, Tobias']",Part Fibre Toxicol,,,True
0eff8cb176dc1e97612266b1ed94badfeab4e575,PMC,Type I Interferon Receptor Deficiency in Dendritic Cells Facilitates Systemic Murine Norovirus Persistence Despite Enhanced Adaptive Immunity,http://dx.doi.org/10.1371/journal.ppat.1005684,PMC4915689,27327515,CC BY,"In order for a virus to persist, there must be a balance between viral replication and immune clearance. It is commonly believed that adaptive immunity drives clearance of viral infections and, thus, dysfunction or viral evasion of adaptive immunity is required for a virus to persist. Type I interferons (IFNs) play pleiotropic roles in the antiviral response, including through innate control of viral replication. Murine norovirus (MNoV) replicates in dendritic cells (DCs) and type I IFN signaling in DCs is important for early control of MNoV replication. We show here that the non-persistent MNoV strain CW3 persists systemically when CD11c positive DCs are unable to respond to type I IFN. Persistence in this setting is associated with increased early viral titers, maintenance of DC numbers, increased expression of DC activation markers and an increase in CD8 T cell and antibody responses. Furthermore, CD8 T cell function is maintained during the persistent phase of infection and adaptive immune cells from persistently infected mice are functional when transferred to Rag1 (-/-) recipients. Finally, increased early replication and persistence are also observed in mixed bone marrow chimeras where only half of the CD11c positive DCs are unable to respond to type I IFN. These findings demonstrate that increased early viral replication due to a cell-intrinsic innate immune deficiency is sufficient for persistence and a functional adaptive immune response is not sufficient for viral clearance.",2016 Jun 21,"['Nice, Timothy J.', 'Osborne, Lisa C.', 'Tomov, Vesselin T.', 'Artis, David', 'Wherry, E. John', 'Virgin, Herbert W.']",PLoS Pathog,,,True
1af8d169cf2d572b46f2b94b1e83c66686973297,PMC,A comprehensive in silico analysis of non-synonymous and regulatory SNPs of human MBL2 gene,http://dx.doi.org/10.1186/s40064-016-2543-4,PMC4916122,27390651,CC BY,"Mannose binding lectin (MBL) is a liver derived protein which plays an important role in innate immunity. Mannose binding lectin gene 2 (MBL2) polymorphisms are reported to be associated with various diseases. In spite of being exhaustively studied molecule, no attempt has been made till date to comprehensively and systematically analyze the SNPs of MBL2 gene. The present study was carried out to identify and prioritize the SNPs of MBL2 gene for further genotyping and functional studies. To predict the possible impact of SNPs on MBL structure and function SNP data obtained from dbSNP database were analyzed using various bioinformatics tools. Out of total 661 SNPs, only 37 validated SNPs having minor allele frequency ≥0.10 were considered for the present study. These 37 SNPs includes one in 3′ near gene, nine in 3′ UTR, one non-synonymous SNP (nsSNP), thirteen intronic SNPs and thirteen in 5′ near gene. From these 37 SNPs, 11 non-coding SNPs were identified to be of functional significance and evolutionary conserved. Out of these, 4 SNPs from 3′ UTR were found to play role in miRNA binding, 7 SNPs from 5′ near and intronic region were predicted to involve in transcription factor binding and expression of MBL2 gene. One nsSNP Gly54Asp (rs1800450) was found to be deleterious and damaging by both SIFT and Polyphen-2 servers and thus affecting MBL2 protein stability and expression. Protein structural analysis with this amino acid variant was performed by using I-TASSER, RAMPAGE, Swiss-PdbViewer, Chimera and I-mutant. Information regarding solvent accessibility, molecular dynamics and energy minimization calculations showed that this variant causes clashes with neighboring amino acids residues that must interfere in the normal triple helix formation of trimeric subunit and further with the normal assembly of MBL oligomeric form, hence decrease in stability. Thus, findings of the present study indicated 12 SNPs of MBL2 gene to be functionally important. Exploration of these variants may provide novel remedial markers for various diseases.",2016 Jun 21,"['Kalia, Namarta', 'Sharma, Aarti', 'Kaur, Manpreet', 'Kamboj, Sukhdev Singh', 'Singh, Jatinder']",Springerplus,,,True
db5333b01a10f165ae516d30f9d1fbf96ab4b841,PMC,Biological function of Foot-and-mouth disease virus non-structural proteins and non-coding elements,http://dx.doi.org/10.1186/s12985-016-0561-z,PMC4917953,27334704,CC BY,"Foot-and-mouth disease virus (FMDV) represses host translation machinery, blocks protein secretion, and cleaves cellular proteins associated with signal transduction and the innate immune response to infection. Non-structural proteins (NSPs) and non-coding elements (NCEs) of FMDV play a critical role in these biological processes. The FMDV virion consists of capsid and nucleic acid. The virus genome is a positive single stranded RNA and encodes a single long open reading frame (ORF) flanked by a long structured 5ʹ-untranslated region (5ʹ-UTR) and a short 3ʹ-UTR. The ORF is translated into a polypeptide chain and processed into four structural proteins (VP1, VP2, VP3, and VP4), 10 NSPs (L(pro), 2A, 2B, 2C, 3A, 3B(1–3), 3C(pro), and 3D(pol)), and some cleavage intermediates. In the past decade, an increasing number of studies have begun to focus on the molecular pathogenesis of FMDV NSPs and NCEs. This review collected recent research progress on the biological functions of these NSPs and NCEs on the replication and host cellular regulation of FMDV to understand the molecular mechanism of host–FMDV interactions and provide perspectives for antiviral strategy and development of novel vaccines.",2016 Jun 22,"['Gao, Yuan', 'Sun, Shi-Qi', 'Guo, Hui-Chen']",Virol J,,,True
8d27cf597c7bb3029c304801e4413396e8731d4b,PMC,Spatial expansions and travelling waves of rabies in vampire bats,http://dx.doi.org/10.1098/rspb.2016.0328,PMC4920313,,CC BY,"A major obstacle to anticipating the cross-species transmission of zoonotic diseases and developing novel strategies for their control is the scarcity of data informing how these pathogens circulate within natural reservoir populations. Vampire bats are the primary reservoir of rabies in Latin America, where the disease remains among the most important viral zoonoses affecting humans and livestock. Unpredictable spatiotemporal dynamics of rabies within bat populations have precluded anticipation of outbreaks and undermined widespread bat culling programs. By analysing 1146 vampire bat-transmitted rabies (VBR) outbreaks in livestock across 12 years in Peru, we demonstrate that viral expansions into historically uninfected zones have doubled the recent burden of VBR. Viral expansions are geographically widespread, but severely constrained by high elevation peaks in the Andes mountains. Within Andean valleys, invasions form wavefronts that are advancing towards large, unvaccinated livestock populations that are heavily bitten by bats, which together will fuel high transmission and mortality. Using spatial models, we forecast the pathways of ongoing VBR epizootics across heterogeneous landscapes. These results directly inform vaccination strategies to mitigate impending viral emergence, reveal VBR as an emerging rather than an enzootic disease and create opportunities to test novel interventions to manage viruses in bat reservoirs.",2016 Jun 15,"['Benavides, Julio A.', 'Valderrama, William', 'Streicker, Daniel G.']",Proc Biol Sci,,,True
acf562f91614c114eaeec07bae37b8130968d3df,PMC,Spatial expansions and travelling waves of rabies in vampire bats,http://dx.doi.org/10.1098/rspb.2016.0328,PMC4920313,,CC BY,"A major obstacle to anticipating the cross-species transmission of zoonotic diseases and developing novel strategies for their control is the scarcity of data informing how these pathogens circulate within natural reservoir populations. Vampire bats are the primary reservoir of rabies in Latin America, where the disease remains among the most important viral zoonoses affecting humans and livestock. Unpredictable spatiotemporal dynamics of rabies within bat populations have precluded anticipation of outbreaks and undermined widespread bat culling programs. By analysing 1146 vampire bat-transmitted rabies (VBR) outbreaks in livestock across 12 years in Peru, we demonstrate that viral expansions into historically uninfected zones have doubled the recent burden of VBR. Viral expansions are geographically widespread, but severely constrained by high elevation peaks in the Andes mountains. Within Andean valleys, invasions form wavefronts that are advancing towards large, unvaccinated livestock populations that are heavily bitten by bats, which together will fuel high transmission and mortality. Using spatial models, we forecast the pathways of ongoing VBR epizootics across heterogeneous landscapes. These results directly inform vaccination strategies to mitigate impending viral emergence, reveal VBR as an emerging rather than an enzootic disease and create opportunities to test novel interventions to manage viruses in bat reservoirs.",2016 Jun 15,"['Benavides, Julio A.', 'Valderrama, William', 'Streicker, Daniel G.']",Proc Biol Sci,,,True
42bb18ca1f49d74b80f2bab85b3878cade647b08,PMC,Comparison of Thermal and Non-Thermal Processing of Swine Feed and the Use of Selected Feed Additives on Inactivation of Porcine Epidemic Diarrhea Virus (PEDV),http://dx.doi.org/10.1371/journal.pone.0158128,PMC4920390,27341670,CC BY,"Infection with porcine epidemic diarrhea virus (PEDV) causes diarrhea, vomiting, and high mortality in suckling pigs. Contaminated feed has been suggested as a vehicle of transmission for PEDV. The objective of this study was to compare thermal and electron beam processing, and the inclusion of feed additives on the inactivation of PEDV in feed. Feed samples were spiked with PEDV and then heated to 120–145°C for up to 30 min or irradiated at 0–50 kGy. Another set of feed samples spiked with PEDV and mixed with Ultracid P (Nutriad), Activate DA (Novus International), KEM-GEST (Kemin Agrifood), Acid Booster (Agri-Nutrition), sugar or salt was incubated at room temperature (~25°C) for up to 21 days. At the end of incubation, the virus titers were determined by inoculation of Vero-81 cells and the virus inactivation kinetics were modeled using the Weibull distribution model. The Weibull kinetic parameter delta represented the time or eBeam dose required to reduce virus concentration by 1 log. For thermal processing, delta values ranged from 16.52 min at 120°C to 1.30 min at 145°C. For eBeam processing, a target dose of 50 kGy reduced PEDV concentration by 3 log. All additives tested were effective in reducing the survival of PEDV when compared with the control sample (delta = 17.23 days). Activate DA (0.81) and KEM-GEST (3.28) produced the fastest inactivation. In conclusion, heating swine feed at temperatures over 130°C or eBeam processing of feed with a dose over 50 kGy are effective processing steps to reduce PEDV survival. Additionally, the inclusion of selected additives can decrease PEDV survivability.",2016 Jun 24,"['Trudeau, Michaela P.', 'Verma, Harsha', 'Sampedro, Fernando', 'Urriola, Pedro E.', 'Shurson, Gerald C.', 'McKelvey, Jessica', 'Pillai, Suresh D.', 'Goyal, Sagar M.']",PLoS One,,,True
87154b31b741f39ec7e34f3590f80b9a01105e33,PMC,Association between ambient temperature and lower urinary tract symptoms: a community-based survey,http://dx.doi.org/10.1590/S1677-5538.IBJU.2015.0159,PMC4920570,27286116,CC BY,"PURPOSE: The aim of this study was to evaluate the individual change of International prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) in each patient by temperature conditions. MATERIALS AND METHODS: The severity of lower urinary tract symptoms (LUTS) was explored using the IPSS and OABSS questionnaires that were completed by 2.486 subjects (923 males and 1.563 females) aged 60 years and older. Korea Meteorological Administration data was used to determine daily average temperature and daily temperature difference on the interview dates at each site. RESULTS: The mean IPSS and mean age for males was 13.45±8.24 and 75.03±6.20 years, respectively. The mean OABSS and mean age for females was 4.41±3.10 and 73.74±6.03years, respectively. Daily average temperature and daily temperature difference ranged from-3.4-28.3(o)C and 2.2-16.9(o)C, respectively. Age was a significantly risk factor for IPSS, OABSS, and QoL (P<0.001, <0.001, and 0.005, respectively). After multiple regression analysis, daily average temperatures did not show a statistically significant change in IPSS and OABSS. Only daily temperature differences were associated with male LUTS. CONCLUSIONS: While LUTS could be worsened in low temperatures generally, IPSS and OABSS were not affected by daily average temperature conditions. Daily temperature differences may be more influential than daily average temperatures.",2016 May-Jun,"['Shim, Sung Ryul', 'Kim, Jae Heon', 'Won, Jong Ho', 'Song, Eun Seop', 'Song, Yun Seob']",Int Braz J Urol,,,True
cf6dbaad6eab542c67cde5670d0fa0a2a65248f8,PMC,"Alphacoronavirus in urban Molossidae and Phyllostomidae bats, Brazil",http://dx.doi.org/10.1186/s12985-016-0569-4,PMC4920988,27342195,CC BY,"BACKGROUND: Bats have been implicated as the main reservoir of coronavirus (CoV). Thus the role of these hosts on the evolution and spread of CoVs currently deserve the attention of emerging diseases surveillance programs. On the view of the interest on and importance of CoVs in bats the occurrence and molecular characterization of CoV were conducted in bats from Brazil. FINDINGS: Three hundred five enteric contents of 29 bat species were tested using a panCoV nested RT-PCR. Nine specimens were positive and eight was suitable for RdRp gene sequencing. RdRp gene phylogeny showed that all CoVs strains from this study cluster in Alphacoronavirus genus, with one Molossidae and one Phlyllostomidae-CoV specific groups. Phylogenetic analyses of two S gene sequences showed a large diversity within the Alphacoronavirus genus. CONCLUSIONS: This study indicated a CoV-to-host specificity and draws attention for CoV detection in Cynomops sp, a potential new reservoir. The phylogenetic analyses indicate that diversity of CoV in bats is higher than previously known.",2016 Jun 24,"['Asano, Karen Miyuki', 'Hora, Aline Santana', 'Scheffer, Karin Côrrea', 'Fahl, Willian Oliveira', 'Iamamoto, Keila', 'Mori, Enio', 'Brandão, Paulo Eduardo']",Virol J,,,True
7fcbdac915f32c243a9c8bc7cc086b2ac65416af,PMC,Immunity-Related Protein Expression and Pathological Lung Damage in Mice Poststimulation with Ambient Particulate Matter from Live Bird Markets,http://dx.doi.org/10.3389/fimmu.2016.00252,PMC4921493,27446082,CC BY,"The objective of this study was to obtain insight into the adverse health effects of airborne particulate matter (PM) collected from live bird markets and to determine whether biological material in PM accounts for immune-related inflammatory response. Mice were exposed to a single or repeated dose of PM, after which the expression of toll-like receptors (TLRs), cytokines, and chemokines in the lungs of infected mice were examined by enzyme-linked immunosorbent assay and histopathological analysis. Results after single and repeated PM stimulation with [Formula: see text] indicated that TLR2 and TLR4 played a dominant role in the inflammatory responses of the lung. Further analysis demonstrated that the expression levels of IL-1β, TNF-α, IFN-γ, IL-8, IP-10, and MCP-1 increased significantly, which could eventually contribute to lung injury. Moreover, biological components in PM were critical in mediating immune-related inflammatory responses and should therefore not be overlooked.",2016 Jun 27,"['Meng, Kai', 'Wu, Bo', 'Gao, Jing', 'Cai, Yumei', 'Yao, Meiling', 'Wei, Liangmeng', 'Chai, Tongjie']",Front Immunol,,,True
bf001dd7a7e2e974fa974607ccbcd9a2de960d2a,PMC,SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice,http://dx.doi.org/10.1038/srep28672,PMC4923882,27349522,CC BY,"During the co-evolution of viruses and their hosts, the viruses have evolved numerous strategies to counter and evade host antiviral immune responses in order to establish a successful infection, replicate and persist in the host. Recently, based on our model of immune signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, we suggested specific molecular mechanisms used by different viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) to modulate the host immune response mediated by members of the family of multichain immune recognition receptors (MIRRs). This family includes T cell receptor (TCR) that is critically involved in immune diseases such as autoimmune arthritis. In the present study, we provide compelling experimental in vivo evidence in support of our hypothesis. Using the SCHOOL approach and the SARS-CoV fusion peptide sequence, we rationally designed a novel immunomodulatory peptide that targets TCR. We showed that this peptide ameliorates collagen-induced arthritis in DBA/1J mice and protects against bone and cartilage damage. Incorporation of the peptide into self-assembling lipopeptide nanoparticles that mimic native human high density lipoproteins significantly increases peptide dosage efficacy. Together, our data further confirm that viral immune evasion strategies that target MIRRs can be transferred to therapeutic strategies that require similar functionalities.",2016 Jun 28,"['Shen, Zu T.', 'Sigalov, Alexander B.']",Sci Rep,,,True
455ddc24431c80dc3b027caf22fc7112e30ff89f,PMC,SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice,http://dx.doi.org/10.1038/srep28672,PMC4923882,27349522,CC BY,"During the co-evolution of viruses and their hosts, the viruses have evolved numerous strategies to counter and evade host antiviral immune responses in order to establish a successful infection, replicate and persist in the host. Recently, based on our model of immune signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, we suggested specific molecular mechanisms used by different viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) to modulate the host immune response mediated by members of the family of multichain immune recognition receptors (MIRRs). This family includes T cell receptor (TCR) that is critically involved in immune diseases such as autoimmune arthritis. In the present study, we provide compelling experimental in vivo evidence in support of our hypothesis. Using the SCHOOL approach and the SARS-CoV fusion peptide sequence, we rationally designed a novel immunomodulatory peptide that targets TCR. We showed that this peptide ameliorates collagen-induced arthritis in DBA/1J mice and protects against bone and cartilage damage. Incorporation of the peptide into self-assembling lipopeptide nanoparticles that mimic native human high density lipoproteins significantly increases peptide dosage efficacy. Together, our data further confirm that viral immune evasion strategies that target MIRRs can be transferred to therapeutic strategies that require similar functionalities.",2016 Jun 28,"['Shen, Zu T.', 'Sigalov, Alexander B.']",Sci Rep,,,False
ec9755d0db388d8a9066baffc9fd33bdf24f5bac,PMC,"Individual Monitoring and Occupational Dose Record Management in China: History, Current Status and Perspectives",http://dx.doi.org/10.3390/ijerph13060558,PMC4924015,27271646,CC BY,"This review paper presents an overview of individual monitoring, as well as the national dose register and dose record management of radiation workers in China. Progress has recently been made on the individual monitoring of radiation workers. A critical analysis of current status and problems in individual monitoring is also presented and necessary future research on individual monitoring, such as the monitoring technology in the form of the ring dosimeters and eye lens dosimeters, is suggested.",2016 Jun 3,"['Wang, Hong-Bo', 'Yu, Hai-Tao', 'Sun, Quan-Fu']",Int J Environ Res Public Health,,,True
365ab3e4ca40537484abf16d4d33d88f63635404,PMC,A Bibliometric Analysis of PubMed Literature on Middle East Respiratory Syndrome,http://dx.doi.org/10.3390/ijerph13060583,PMC4924040,27304963,CC BY,"Middle East Respiratory Syndrome (MERS), a pandemic threat to human beings, has aroused huge concern worldwide, but no bibliometric studies have been conducted on MERS research. The aim of this study was to map research productivity on the disease based on the articles indexed in PubMed. The articles related to MERS dated from 2012 to 2015 were retrieved from PubMed. The articles were classified into three categories according to their focus. Publication outputs were assessed and frequently used terms were mapped using the VOS viewer software. A total of 443 articles were included for analysis. They were published in 162 journals, with Journal of Virology being the most productive (44 articles; 9.9%) and by six types of organizations, with universities being the most productive (276 articles; 62.4%).The largest proportion of the articles focused on basic medical sciences and clinical studies (47.2%) and those on prevention and control ranked third (26.2%), with those on other focuses coming in between (26.6%). The articles on prevention and control had the highest mean rank for impact factor (IF) (226.34), followed by those on basic medical sciences and clinical studies (180.23) and those on other focuses (168.03). The mean rank differences were statistically significant (p = 0.000). Besides, “conronavirus”, “case”, “transmission” and “detection” were found to be the most frequently used terms. The findings of this first bibliometric study on MERS suggest that the prevention and control of the disease has become a big concern and related research should be strengthened.",2016 Jun 13,"['Wang, Zhengting', 'Chen, Yongdi', 'Cai, Gaofeng', 'Jiang, Zhenggang', 'Liu, Kui', 'Chen, Bin', 'Jiang, Jianmin', 'Gu, Hua']",Int J Environ Res Public Health,,,True
97472ef04ad420815a0fa19076162835fad47af4,PMC,Acquisition of tumorigenic potential and enhancement of angiogenesis in pulmonary stem/progenitor cells through Oct-4 hyperexpression,http://dx.doi.org/10.18632/oncotarget.7285,PMC4924688,26871601,CC BY,"Cancer stem cells, also known as cancer initiating cells (CICs), are considered to be responsible for tumor growth and chemoresistance. Different hypotheses have been proposed to explain the origin of CICs, including mutations in adult stem/progenitor cells or the acquisition of stem-like characteristics in differentiated cells; however, studies have yielded conflicting identification for CICs and have little information for the origin to generate CICs. Part of the difficulty in identifying CICs may stem from the fact that the CICs studied have been largely derived from cancer cell lines or well-developed tumors. In previous studies, we have reported the enrichment of mouse pulmonary stem/progenitor cells (mPSCs) by using serum-free primary selection culture followed by FACS isolation using the coxsackievirus/adenovirus receptor (CAR) as the positive selection marker. Here, we demonstrated that overexpression of the pluripotent transcription factor Oct-4 is sufficient to induce CAR(+)/mPSCs transformation, which we name CAR(+)/mPSCs(Oct-4_hi). These transformed cells possess cancer initiating and chemoresistance potential, as well as exhibiting remarkable expression of certain proangiogenic factors, including angiopoietins (ANGs) and VEGF, and enhanced angiogenic potential. Moreover, CAR(+)/mPSCs(Oct-4_hi) actively participated in tumor blood vessel formation and triggered a novel angiogenic mechanism, the angiopoietins/Tie2 signaling pathway. These study provide critical evidence supporting the possible origin to generate CICs, and help elucidate the pathways responsible for CICs-mediated blood vessel formation.",2016 Feb 9,"['Gu, Sing-Yi', 'Ho, Choa-Chi', 'Huang, Yung-Kang', 'Chen, Huei-Wen', 'Wang, Yu-Chi', 'Kuo, Chia-Yu', 'Teng, Shu-Chun', 'Fu, Wen-Mei', 'Yang, Pan-Chyr', 'Wu, Cheng-Wen', 'Peng, Fu-Chuo', 'Ling, Thai-Yen']",Oncotarget,,,True
40cc2ba8d307f9dc0d11f4c57f2f22ff8c442057,PMC,Acquisition of tumorigenic potential and enhancement of angiogenesis in pulmonary stem/progenitor cells through Oct-4 hyperexpression,http://dx.doi.org/10.18632/oncotarget.7285,PMC4924688,26871601,CC BY,"Cancer stem cells, also known as cancer initiating cells (CICs), are considered to be responsible for tumor growth and chemoresistance. Different hypotheses have been proposed to explain the origin of CICs, including mutations in adult stem/progenitor cells or the acquisition of stem-like characteristics in differentiated cells; however, studies have yielded conflicting identification for CICs and have little information for the origin to generate CICs. Part of the difficulty in identifying CICs may stem from the fact that the CICs studied have been largely derived from cancer cell lines or well-developed tumors. In previous studies, we have reported the enrichment of mouse pulmonary stem/progenitor cells (mPSCs) by using serum-free primary selection culture followed by FACS isolation using the coxsackievirus/adenovirus receptor (CAR) as the positive selection marker. Here, we demonstrated that overexpression of the pluripotent transcription factor Oct-4 is sufficient to induce CAR(+)/mPSCs transformation, which we name CAR(+)/mPSCs(Oct-4_hi). These transformed cells possess cancer initiating and chemoresistance potential, as well as exhibiting remarkable expression of certain proangiogenic factors, including angiopoietins (ANGs) and VEGF, and enhanced angiogenic potential. Moreover, CAR(+)/mPSCs(Oct-4_hi) actively participated in tumor blood vessel formation and triggered a novel angiogenic mechanism, the angiopoietins/Tie2 signaling pathway. These study provide critical evidence supporting the possible origin to generate CICs, and help elucidate the pathways responsible for CICs-mediated blood vessel formation.",2016 Feb 9,"['Gu, Sing-Yi', 'Ho, Choa-Chi', 'Huang, Yung-Kang', 'Chen, Huei-Wen', 'Wang, Yu-Chi', 'Kuo, Chia-Yu', 'Teng, Shu-Chun', 'Fu, Wen-Mei', 'Yang, Pan-Chyr', 'Wu, Cheng-Wen', 'Peng, Fu-Chuo', 'Ling, Thai-Yen']",Oncotarget,,,False
4ee51bb838b0cdc2e59317a4b837f2997795b665,PMC,Hospitalization Risk Due to Respiratory Illness Associated with Genetic Variation at IFITM3 in Patients with Influenza A(H1N1)pdm09 Infection: A Case-Control Study,http://dx.doi.org/10.1371/journal.pone.0158181,PMC4924831,27351739,CC BY,"BACKGROUND: Recent studies suggest an association between the Interferon Inducible Transmembrane 3 (IFITM3) rs12252 variant and the course of influenza infection. However, it is not clear whether the reported association relates to influenza infection severity. The aim of this study was to estimate the hospitalization risk associated with this variant in Influenza Like Illness (ILI) patients during the H1N1 pandemic influenza. METHODS: A case-control genetic association study was performed, using nasopharyngeal/oropharyngeal swabs collected during the H1N1 pandemic influenza. Laboratory diagnosis of influenza infection was performed by RT-PCR, the IFITM3 rs12252 was genotyped by RFLP and tested for association with hospitalization. Conditional logistic regression was performed to calculate the confounder-adjusted odds ratio of hospitalization associated with IFITM3 rs12252. RESULTS: We selected 312 ILI cases and 624 matched non-hospitalized controls. Within ILI Influenza A(H1N1)pdm09 positive patients, no statistical significant association was found between the variant and the hospitalization risk (Adjusted OR: 0.73 (95%CI: 0.33–1.50)). Regarding ILI Influenza A(H1N1)pdm09 negative patients, CT/CC genotype carriers had a higher risk of being hospitalized than patients with TT genotype (Adjusted OR: 2.54 (95%CI: 1.54–4.19)). CONCLUSIONS: The IFITM3 rs12252 variant was associated with respiratory infection hospitalization but not specifically in patients infected with Influenza A(H1N1)pdm09.",2016 Jun 28,"['Gaio, Vânia', 'Nunes, Baltazar', 'Pechirra, Pedro', 'Conde, Patrícia', 'Guiomar, Raquel', 'Dias, Carlos Matias', 'Barreto, Marta']",PLoS One,,,True
f2f9088055600d4160e36db5cb6ea000916390a3,PMC,A Global Champion for Health—WHO’s Next?,http://dx.doi.org/10.1371/journal.pmed.1002059,PMC4924837,27351843,CC BY,"In this month’s editorial, the PLOS Medicine Editors propose ideal qualities for the World Health Organization's next Director General, for whom the selection process is now underway.",2016 Jun 28,,PLoS Med,,,True
d29ac40afbb28f3dff1d4923aae6c01299399334,PMC,A Tale of Two RNAs during Viral Infection: How Viruses Antagonize mRNAs and Small Non-Coding RNAs in The Host Cell,http://dx.doi.org/10.3390/v8060154,PMC4926174,27271653,CC BY,"Viral infection initiates an array of changes in host gene expression. Many viruses dampen host protein expression and attempt to evade the host anti-viral defense machinery. Host gene expression is suppressed at several stages of host messenger RNA (mRNA) formation including selective degradation of translationally competent messenger RNAs. Besides mRNAs, host cells also express a variety of noncoding RNAs, including small RNAs, that may also be subject to inhibition upon viral infection. In this review we focused on different ways viruses antagonize coding and noncoding RNAs in the host cell to its advantage.",2016 Jun 2,"['Herbert, Kristina M.', 'Nag, Anita']",Viruses,,,True
2ca39f3627583a75a4cd19f770b697714a89b686,PMC,Endoplasmic Reticulum: The Favorite Intracellular Niche for Viral Replication and Assembly,http://dx.doi.org/10.3390/v8060160,PMC4926180,27338443,CC BY,"The endoplasmic reticulum (ER) is the largest intracellular organelle. It forms a complex network of continuous sheets and tubules, extending from the nuclear envelope (NE) to the plasma membrane. This network is frequently perturbed by positive-strand RNA viruses utilizing the ER to create membranous replication factories (RFs), where amplification of their genomes occurs. In addition, many enveloped viruses assemble progeny virions in association with ER membranes, and viruses replicating in the nucleus need to overcome the NE barrier, requiring transient changes of the NE morphology. This review first summarizes some key aspects of ER morphology and then focuses on the exploitation of the ER by viruses for the sake of promoting the different steps of their replication cycles.",2016 Jun 7,"['Romero-Brey, Inés', 'Bartenschlager, Ralf']",Viruses,,,True
441656e0f7eea90edc2e3cb7e72d362b55e97ce3,PMC,Phleboviruses and the Type I Interferon Response,http://dx.doi.org/10.3390/v8060174,PMC4926194,27338447,CC BY,"The genus Phlebovirus of the family Bunyaviridae contains a number of emerging virus species which pose a threat to both human and animal health. Most prominent members include Rift Valley fever virus (RVFV), sandfly fever Naples virus (SFNV), sandfly fever Sicilian virus (SFSV), Toscana virus (TOSV), Punta Toro virus (PTV), and the two new members severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV). The nonstructural protein NSs is well established as the main phleboviral virulence factor in the mammalian host. NSs acts as antagonist of the antiviral type I interferon (IFN) system. Recent progress in the elucidation of the molecular functions of a growing list of NSs proteins highlights the astonishing variety of strategies employed by phleboviruses to evade the IFN system.",2016 Jun 22,"['Wuerth, Jennifer Deborah', 'Weber, Friedemann']",Viruses,,,True
09242b23825a9c7e09660df99494b673e5abea3e,PMC,Membrane protein assembly: two cytoplasmic phosphorylated serine sites of Vpu from HIV-1 affect oligomerization,http://dx.doi.org/10.1038/srep28866,PMC4926278,27353136,CC BY,"Viral protein U (Vpu) encoded by human immunodeficiency virus type 1 (HIV-1) is a short integral membrane protein which is known to self-assemble within the lipid membrane and associate with host factors during the HIV-1 infectivity cycle. In this study, full-length Vpu (M group) from clone NL4-3 was over-expressed in human cells and purified in an oligomeric state. Various single and double mutations were constructed on its phosphorylation sites to mimic different degrees of phosphorylation. Size exclusion chromatography of wild-type Vpu and mutants indicated that the smallest assembly unit of Vpu was a dimer and over time Vpu formed higher oligomers. The rate of oligomerization increased when (i) the degree of phosphorylation at serines 52 and 56 was decreased and (ii) when the ionic strength was increased indicating that the cytoplasmic domain of Vpu affects oligomerization. Coarse-grained molecular dynamic simulations with models of wild-type and mutant Vpu in a hydrated lipid bilayer supported the experimental data in demonstrating that, in addition to a previously known role in downregulation of host factors, the phosphorylation sites of Vpu also modulate oligomerization.",2016 Jun 29,"['Chen, Chin-Pei', 'Lin, Meng-Han', 'Chan, Ya-Ting', 'Chen, Li-Chyong', 'Ma, Che', 'Fischer, Wolfgang B.']",Sci Rep,,,True
b18ff7b65ed56a87c0c0de1ee312b8a0ddb51e4c,PMC,Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice,http://dx.doi.org/10.1038/srep28950,PMC4928056,27358191,CC BY,"Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) has been implicated as a co-chaperone and regulator of androgen and growth hormone receptor (AR, GHR) signalling. We investigated the functional consequences of partial and full Sgta ablation in vivo using Cre-lox Sgta-null mice. Sgta(+/−) breeders generated viable Sgta(−/−) offspring, but at less than Mendelian expectancy. Sgta(−/−) breeders were subfertile with small litters and higher neonatal death (P < 0.02). Body size was significantly and proportionately smaller in male and female Sgta(−/−) (vs WT, Sgta(+/−) P < 0.001) from d19. Serum IGF-1 levels were genotype- and sex-dependent. Food intake, muscle and bone mass and adiposity were unchanged in Sgta(−/−). Vital and sex organs had normal relative weight, morphology and histology, although certain androgen-sensitive measures such as penis and preputial size, and testis descent, were greater in Sgta(−/−). Expression of AR and its targets remained largely unchanged, although AR localisation was genotype- and tissue-dependent. Generally expression of other TPR-containing proteins was unchanged. In conclusion, this thorough investigation of SGTA-null mutation reports a mild phenotype of reduced body size. The model’s full potential likely will be realised by genetic crosses with other models to interrogate the role of SGTA in the many diseases in which it has been implicated.",2016 Jun 30,"['Philp, Lisa K.', 'Day, Tanya K.', 'Butler, Miriam S.', 'Laven-Law, Geraldine', 'Jindal, Shalini', 'Hickey, Theresa E.', 'Scher, Howard I.', 'Butler, Lisa M.', 'Tilley, Wayne D.']",Sci Rep,,,True
9d465783b4ea9f810aa9608632a594d3e80dca03,PMC,Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice,http://dx.doi.org/10.1038/srep28950,PMC4928056,27358191,CC BY,"Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) has been implicated as a co-chaperone and regulator of androgen and growth hormone receptor (AR, GHR) signalling. We investigated the functional consequences of partial and full Sgta ablation in vivo using Cre-lox Sgta-null mice. Sgta(+/−) breeders generated viable Sgta(−/−) offspring, but at less than Mendelian expectancy. Sgta(−/−) breeders were subfertile with small litters and higher neonatal death (P < 0.02). Body size was significantly and proportionately smaller in male and female Sgta(−/−) (vs WT, Sgta(+/−) P < 0.001) from d19. Serum IGF-1 levels were genotype- and sex-dependent. Food intake, muscle and bone mass and adiposity were unchanged in Sgta(−/−). Vital and sex organs had normal relative weight, morphology and histology, although certain androgen-sensitive measures such as penis and preputial size, and testis descent, were greater in Sgta(−/−). Expression of AR and its targets remained largely unchanged, although AR localisation was genotype- and tissue-dependent. Generally expression of other TPR-containing proteins was unchanged. In conclusion, this thorough investigation of SGTA-null mutation reports a mild phenotype of reduced body size. The model’s full potential likely will be realised by genetic crosses with other models to interrogate the role of SGTA in the many diseases in which it has been implicated.",2016 Jun 30,"['Philp, Lisa K.', 'Day, Tanya K.', 'Butler, Miriam S.', 'Laven-Law, Geraldine', 'Jindal, Shalini', 'Hickey, Theresa E.', 'Scher, Howard I.', 'Butler, Lisa M.', 'Tilley, Wayne D.']",Sci Rep,,,False
1dfc1d885254d7df5f71844b7de87fb6c9539662,PMC,Isolation and characterization of porcine epidemic diarrhea virus associated with the 2014 disease outbreak in Mexico: case report,http://dx.doi.org/10.1186/s12917-016-0763-z,PMC4928271,27357720,CC BY,"BACKGROUND: Interest in porcine epidemic diarrhea has grown since the 2013 outbreak in the United States caused major losses, with mortality rates up to 100 % in suckling piglets. In Mexico, an outbreak of porcine epidemic diarrhea, characterized by 100 % mortality in piglets, began in March 2014 in the State of Mexico. METHODS: The aim of this study was to confirm and identify porcine epidemic diarrhea virus (PEDV) in samples from piglets with suggestive clinical signs using virological, histological, and molecular techniques. Necropsy was performed on 13 piglets from two litters with initial and advanced clinical signs. Suggestive lesions of acute infection with PEDV were detected in histological sections of the small and large bowels; specifically, multiple virus particles with visible crown-shaped projections were observed using electron microscopy and negative staining. Viral isolation was performed in Vero cells with trypsin. Infection was monitored by observation of cytopathic effect, and titration was determined by TCID(50)/ml. The presence of the PEDV in cultures and clinical samples was confirmed by RT-PCR amplification and sequencing of a 651-bp segment of the S glycoprotein gene, as well as a 681-bp matrix protein gene. RESULTS: The nucleotide sequence analysis of the Mexican isolates showed marked homology to viruses that circulated in 2013 in Colorado, USA. CONCLUSIONS: In this paper we confirm the isolation and characterization of PEDV from animals with early and advanced clinical signs.",2016 Jun 29,"['Trujillo-Ortega, María Elena', 'Beltrán-Figueroa, Rolando', 'García-Hernández, Montserrat Elemi', 'Juárez-Ramírez, Mireya', 'Sotomayor-González, Alicia', 'Hernández-Villegas, Erika N.', 'Becerra-Hernández, José F.', 'Sarmiento-Silva, Rosa Elena']",BMC Vet Res,,,True
c760ba658ba0d10b96cf738e04f83f22bd15f3a3,PMC,Evidence of Aujeszky’s disease in wild boar in Serbia,http://dx.doi.org/10.1186/s12917-016-0758-9,PMC4928280,27357597,CC BY,"BACKGROUND: Aujeszky’s disease is a viral disease of suids caused by Suid Herpesvirus 1. The disease has worldwide distribution with significant economic impact. In Serbia, there is neither an Aujeszky’s disease eradication nor national vaccination programme of domestic pigs. Since clinical symptoms of Aujeszky’s disease are not specific, it is important to establish a link between clinical signs and presence of ADV active infection in wild boars. The aim of this study was to investigate the possibility of active infection within wild boar showing signs of ADV and also to examine relationship between isolates from domestic pigs and wild boar. Having in mind that virus has not been previously isolated from wild boars in Serbia, we report the first isolation of Suid Herpesvirus 1 from this species in Serbia. RESULTS: Tissue and serum samples from 40 wild boars from eastern Serbia were examined for evidence of Aujeszky’s disease (AD). Suid Herpesvirus 1 (SHV1), the cause of AD was isolated on PK15 cell line from three tissue samples, inducing cytopathic effect (CPE) with syncytia forming, and viral genome was detected by polymerase chain reaction (PCR) in eight samples. Genetic analysis of us4, us9 and ul49.5 partial sequences showed high homology between ADV isolates from wild boars and between isolates from wild boars and domestic animals. Neutralizing antibodies were not detected by virus neutralisation test (VNT) in sera from four out of eight PCR positive wild boars suggesting recent infection in those animals. CONCLUSIONS: This is the first demonstration of Aujeszky’s disease virus (ADV) in the wild boar population in Serbia although seroconversion has been detected previously.",2016 Jun 30,"['Milicevic, V.', 'Radojicic, S.', 'Valcic, M.', 'Ivovic, V.', 'Radosavljevic, V.']",BMC Vet Res,,,True
78ef6e101522626b8c7c7621ec50146ab57cf488,PMC,Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung,http://dx.doi.org/10.3389/fimmu.2016.00258,PMC4928648,27446088,CC BY,"Following pulmonary inflammation, leukocytes that infiltrate the lung often assemble into structures known as inducible Bronchus-Associated Lymphoid Tissue (iBALT). Like conventional lymphoid organs, areas of iBALT have segregated B and T cell areas, specialized stromal cells, high endothelial venules, and lymphatic vessels. After inflammation is resolved, iBALT is maintained for months, independently of inflammation. Once iBALT is formed, it participates in immune responses to pulmonary antigens, including those that are unrelated to the iBALT-initiating antigen, and often alters the clinical course of disease. However, the mechanisms that govern immune responses in iBALT and determine how iBALT impacts local and systemic immunity are poorly understood. Here, we review our current understanding of iBALT formation and discuss how iBALT participates in pulmonary immunity.",2016 Jun 30,"['Hwang, Ji Young', 'Randall, Troy D.', 'Silva-Sanchez, Aaron']",Front Immunol,,,True
9d8252afd663371d83c2e28943f2df1bec3f4780,PMC,Dissecting Virus Infectious Cycles by Cryo-Electron Microscopy,http://dx.doi.org/10.1371/journal.ppat.1005625,PMC4928862,27362353,CC BY,,2016 Jun 30,"['Lee, Kelly K.', 'Gui, Long']",PLoS Pathog,,,True
8ad6fe3d0031f1dffb84dec640ac0bb7c5ba84fb,PMC,Alzheimer’s disease Advax(CpG)- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules,http://dx.doi.org/10.1038/srep28912,PMC4929459,27363809,CC BY,"Although β-amyloid (Aβ) may be the primary driver of Alzheimer’s disease (AD) pathology, accumulation of pathological tau correlates with dementia in AD patients. Thus, the prevention/inhibition of AD may require vaccine/s targeting Aβ and tau simultaneously or sequentially. Since high antibody titers are required for AD vaccine efficacy, we have decided to generate vaccines, targeting Aβ (AV-1959R), Tau (AV-1980R) or Aβ/tau (AV-1953R) B cell epitopes, based on immunogenic MultiTEP platform and evaluate the immunogenicity of these vaccines formulated with Advax(CpG), delta inulin, Alhydrogel(®), Montanide-ISA51, Montanide-ISA720, MPLA-SM pharmaceutical grade adjuvants. Formulation of AV-1959R in Advax(CpG) induced the highest cellular and humoral immune responses in mice. The dual-epitope vaccine, AV-1953R, or the combination of AV-1959R and AV-1980R vaccines formulated with Advax(CpG) induced robust antibody responses against various forms of both, Aβ and tau pathological molecules. While anti-Aβ antibody titers after AV-1953R immunization were similar to that in mice vaccinated with AV-1959R or AV-1959R/AV-1980R combination, anti-tau titers were significantly lower after AV-1953R injection when compared to the AV-1980R or AV-1959R/AV-1980R. In silico 3D-modeling provided insight into the differences in immunogenicity of these vaccine constructs. In sum, AV-1959R and AV-1980R formulated with Advax(CpG) adjuvant were identified as promising immunogenic vaccines for ongoing pre-clinical assessment and future human clinical trials.",2016 Jul 1,"['Davtyan, Hayk', 'Zagorski, Karen', 'Rajapaksha, Harinda', 'Hovakimyan, Armine', 'Davtyan, Arpine', 'Petrushina, Irina', 'Kazarian, Konstantin', 'Cribbs, David H.', 'Petrovsky, Nikolai', 'Agadjanyan, Michael G.', 'Ghochikyan, Anahit']",Sci Rep,,,True
9933e9bd314173e10397a75c88d68c482a122289,PMC,Alzheimer’s disease Advax(CpG)- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules,http://dx.doi.org/10.1038/srep28912,PMC4929459,27363809,CC BY,"Although β-amyloid (Aβ) may be the primary driver of Alzheimer’s disease (AD) pathology, accumulation of pathological tau correlates with dementia in AD patients. Thus, the prevention/inhibition of AD may require vaccine/s targeting Aβ and tau simultaneously or sequentially. Since high antibody titers are required for AD vaccine efficacy, we have decided to generate vaccines, targeting Aβ (AV-1959R), Tau (AV-1980R) or Aβ/tau (AV-1953R) B cell epitopes, based on immunogenic MultiTEP platform and evaluate the immunogenicity of these vaccines formulated with Advax(CpG), delta inulin, Alhydrogel(®), Montanide-ISA51, Montanide-ISA720, MPLA-SM pharmaceutical grade adjuvants. Formulation of AV-1959R in Advax(CpG) induced the highest cellular and humoral immune responses in mice. The dual-epitope vaccine, AV-1953R, or the combination of AV-1959R and AV-1980R vaccines formulated with Advax(CpG) induced robust antibody responses against various forms of both, Aβ and tau pathological molecules. While anti-Aβ antibody titers after AV-1953R immunization were similar to that in mice vaccinated with AV-1959R or AV-1959R/AV-1980R combination, anti-tau titers were significantly lower after AV-1953R injection when compared to the AV-1980R or AV-1959R/AV-1980R. In silico 3D-modeling provided insight into the differences in immunogenicity of these vaccine constructs. In sum, AV-1959R and AV-1980R formulated with Advax(CpG) adjuvant were identified as promising immunogenic vaccines for ongoing pre-clinical assessment and future human clinical trials.",2016 Jul 1,"['Davtyan, Hayk', 'Zagorski, Karen', 'Rajapaksha, Harinda', 'Hovakimyan, Armine', 'Davtyan, Arpine', 'Petrushina, Irina', 'Kazarian, Konstantin', 'Cribbs, David H.', 'Petrovsky, Nikolai', 'Agadjanyan, Michael G.', 'Ghochikyan, Anahit']",Sci Rep,,,False
6907124581ac28f6712e3676396cfc4a3b8a9502,PMC,Accelerating skin wound healing by M-CSF through generating SSEA-1 and -3 stem cells in the injured sites,http://dx.doi.org/10.1038/srep28979,PMC4929493,27363517,CC BY,"Wound healing is a complicated process requiring the collaborative efforts of different cell lineages. Our recent studies have found that one subset of hematopoietic cells can be induced to dedifferentiate into multipotent stem cells by means of a proliferating fibroblast releasable factor, M-CSF. Understanding the importance of stem cells on skin wound healing, here we evaluate the biological significance of M-CSF on skin wound healing. In an in vivo mouse skin excisional wound model, we found that SSEA-positive stem cells were present in wounded but not normal skin. After isolating skin cells from either normal or wounded skin by collagenase digestion, and analyzing the SSEA-1 positive cells by flow cytometry, we found a significant increase in the number of SSEA-1 positive cells in wounded skin. Topical application of M-CSF in skin wounds accelerated healing remarkably, while application of M-CSF-neutralizing antibody slowed wound healing. Furthermore, injection of EGFP-labeled hematopoietic cell-derived stem cells generated from M-CSF treated splenocytes resulted in EGFP-labeled cells being enriched in the skin wound site and further differentiated into functional organ-specific cells. Together, these data demonstrated that M-CSF makes a significant contribution to the healing process by inducing hematopoietic cell dedifferentiation into stem cells.",2016 Jul 1,"['Li, Yunyuan', 'Jalili, Reza Baradar', 'Ghahary, Aziz']",Sci Rep,,,True
2c35971bf39265b7ccb2721d0079e0a4fd019ad1,PMC,Accelerating skin wound healing by M-CSF through generating SSEA-1 and -3 stem cells in the injured sites,http://dx.doi.org/10.1038/srep28979,PMC4929493,27363517,CC BY,"Wound healing is a complicated process requiring the collaborative efforts of different cell lineages. Our recent studies have found that one subset of hematopoietic cells can be induced to dedifferentiate into multipotent stem cells by means of a proliferating fibroblast releasable factor, M-CSF. Understanding the importance of stem cells on skin wound healing, here we evaluate the biological significance of M-CSF on skin wound healing. In an in vivo mouse skin excisional wound model, we found that SSEA-positive stem cells were present in wounded but not normal skin. After isolating skin cells from either normal or wounded skin by collagenase digestion, and analyzing the SSEA-1 positive cells by flow cytometry, we found a significant increase in the number of SSEA-1 positive cells in wounded skin. Topical application of M-CSF in skin wounds accelerated healing remarkably, while application of M-CSF-neutralizing antibody slowed wound healing. Furthermore, injection of EGFP-labeled hematopoietic cell-derived stem cells generated from M-CSF treated splenocytes resulted in EGFP-labeled cells being enriched in the skin wound site and further differentiated into functional organ-specific cells. Together, these data demonstrated that M-CSF makes a significant contribution to the healing process by inducing hematopoietic cell dedifferentiation into stem cells.",2016 Jul 1,"['Li, Yunyuan', 'Jalili, Reza Baradar', 'Ghahary, Aziz']",Sci Rep,,,False
b293192e82a70515cb199bca870a9fe2ca9b081d,PMC,Nasopharyngeal microbiota composition of children is related to the frequency of upper respiratory infection and acute sinusitis,http://dx.doi.org/10.1186/s40168-016-0179-9,PMC4929776,27364497,CC BY,"BACKGROUND: Upper respiratory infections (URI) and their complications are a major healthcare burden for pediatric populations. Although the microbiology of the nasopharynx is an important determinant of the complications of URI, little is known of the nasopharyngeal (NP) microbiota of children, the factors that affect its composition, and its precise relationship with URI. RESULTS: Healthy children (n = 47) aged 49–84 months from a prospective cohort study based in Wisconsin, USA, were examined. Demographic and clinical data and NP swab samples were obtained from participants upon entry to the study. All NP samples were profiled for bacterial microbiota using a phylogenetic microarray, and these data were related to demographic characteristics and upper respiratory health outcomes. The composition of the NP bacterial community of children was significantly related prior to the history of acute sinusitis (R(2) = 0.070, P < 0.009). History of acute sinusitis was associated with significant depletion in relative abundance of taxa including Faecalibacterium prausnitzii and Akkermansia spp. and enrichment of Moraxella nonliquefaciens. Enrichment of M. nonliquefaciens was also a characteristic of baseline NP samples of children who subsequently developed acute sinusitis over the 1-year study period. Time to develop URI was significantly positively correlated with NP diversity, and children who experienced more frequent URIs exhibited significantly diminished NP microbiota diversity (P ≤ 0.05). CONCLUSIONS: These preliminary data suggest that previous history of acute sinusitis influences the composition of the NP microbiota, characterized by a depletion in relative abundance of specific taxa. Diminished diversity was associated with more frequent URIs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-016-0179-9) contains supplementary material, which is available to authorized users.",2016 Jul 1,"['Santee, Clark A.', 'Nagalingam, Nabeetha A.', 'Faruqi, Ali A.', 'DeMuri, Gregory P.', 'Gern, James E.', 'Wald, Ellen R.', 'Lynch, Susan V.']",Microbiome,,,True
0ddcfc9bedfb0a87a7221dd2448bd41d3ba9cc51,PMC,How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?,http://dx.doi.org/10.1371/journal.pone.0158237,PMC4930163,27367230,CC BY,"Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements.",2016 Jul 1,"['Vegvari, Carolin', 'Hadjichrysanthou, Christoforos', 'Cauët, Emilie', 'Lawrence, Emma', 'Cori, Anne', 'de Wolf, Frank', 'Anderson, Roy M.']",PLoS One,,,True
73fcc68f1fe5bf9cae21d939f459968ebed64411,PMC,Hepatitis C Virus Core Protein Promotes miR-122 Destabilization by Inhibiting GLD-2,http://dx.doi.org/10.1371/journal.ppat.1005714,PMC4930175,27366906,CC BY,"The liver-specific microRNA miR-122, which has essential roles in liver development and metabolism, is a key proviral factor for hepatitis C virus (HCV). Despite its crucial role in the liver and HCV life cycle, little is known about the molecular mechanism of miR-122 expression regulation by HCV infection. Here, we show that the HCV core protein downregulates the abundance of miR-122 by promoting its destabilization via the inhibition of GLD-2, a non-canonical cytoplasmic poly(A) polymerase. The decrease in miR-122 expression resulted in the dysregulation of the known functions of miR-122, including its proviral activity for HCV. By high-throughput sequencing of small RNAs from human liver biopsies, we found that the 22-nucleotide (nt) prototype miR-122 is modified at its 3′ end by 3′-terminal non-templated and templated nucleotide additions. Remarkably, the proportion of miR-122 isomers bearing a single nucleotide tail of any ribonucleotide decreased in liver specimens from patients with HCV. We found that these single-nucleotide-tailed miR-122 isomers display increased miRNA activity and stability over the 22-nt prototype miR-122 and that the 3′-terminal extension is catalyzed by the unique terminal nucleotidyl transferase activity of GLD-2, which is capable of adding any single ribonucleotide without preference of adenylate to the miR-122 3′ end. The HCV core protein specifically inhibited GLD-2, and its interaction with GLD-2 in the cytoplasm was found to be responsible for miR-122 downregulation. Collectively, our results provide new insights into the regulatory role of the HCV core protein in controlling viral RNA abundance and miR-122 functions through miR-122 stability modulation.",2016 Jul 1,"['Kim, Geon-Woo', 'Lee, Seung-Hoon', 'Cho, Hee', 'Kim, Minwoo', 'Shin, Eui-Cheol', 'Oh, Jong-Won']",PLoS Pathog,,,True
e0111854ce52152339b685712b1a2843e3f1b839,PMC,Nucleolin interacts with influenza A nucleoprotein and contributes to viral ribonucleoprotein complexes nuclear trafficking and efficient influenza viral replication,http://dx.doi.org/10.1038/srep29006,PMC4931502,27373907,CC BY,"Influenza viruses replicate their single-stranded RNA genomes in the nucleus of infected cells and these replicated genomes (vRNPs) are then exported from the nucleus to the cytoplasm and plasma membrane before budding. To achieve this export, influenza viruses hijack the host cell export machinery. However, the complete mechanisms underlying this hijacking remain not fully understood. We have previously shown that influenza viruses induce a marked alteration of the nucleus during the time-course of infection and notably in the nucleolar compartment. In this study, we discovered that a major nucleolar component, called nucleolin, is required for an efficient export of vRNPs and viral replication. We have notably shown that nucleolin interacts with the viral nucleoprotein (NP) that mainly constitutes vRNPs. Our results suggest that this interaction could allow vRNPs to “catch” the host cell export machinery, a necessary step for viral replication.",2016 Jul 4,"['Terrier, Olivier', 'Carron, Coralie', 'De Chassey, Benoît', 'Dubois, Julia', 'Traversier, Aurélien', 'Julien, Thomas', 'Cartet, Gaëlle', 'Proust, Anaïs', 'Hacot, Sabine', 'Ressnikoff, Denis', 'Lotteau, Vincent', 'Lina, Bruno', 'Diaz, Jean-Jacques', 'Moules, Vincent', 'Rosa-Calatrava, Manuel']",Sci Rep,,,True
47f27a1405f69dd7569f6b5d2f0f73b72fcf4c38,PMC,Nucleolin interacts with influenza A nucleoprotein and contributes to viral ribonucleoprotein complexes nuclear trafficking and efficient influenza viral replication,http://dx.doi.org/10.1038/srep29006,PMC4931502,27373907,CC BY,"Influenza viruses replicate their single-stranded RNA genomes in the nucleus of infected cells and these replicated genomes (vRNPs) are then exported from the nucleus to the cytoplasm and plasma membrane before budding. To achieve this export, influenza viruses hijack the host cell export machinery. However, the complete mechanisms underlying this hijacking remain not fully understood. We have previously shown that influenza viruses induce a marked alteration of the nucleus during the time-course of infection and notably in the nucleolar compartment. In this study, we discovered that a major nucleolar component, called nucleolin, is required for an efficient export of vRNPs and viral replication. We have notably shown that nucleolin interacts with the viral nucleoprotein (NP) that mainly constitutes vRNPs. Our results suggest that this interaction could allow vRNPs to “catch” the host cell export machinery, a necessary step for viral replication.",2016 Jul 4,"['Terrier, Olivier', 'Carron, Coralie', 'De Chassey, Benoît', 'Dubois, Julia', 'Traversier, Aurélien', 'Julien, Thomas', 'Cartet, Gaëlle', 'Proust, Anaïs', 'Hacot, Sabine', 'Ressnikoff, Denis', 'Lotteau, Vincent', 'Lina, Bruno', 'Diaz, Jean-Jacques', 'Moules, Vincent', 'Rosa-Calatrava, Manuel']",Sci Rep,,,False
9033d46664d7ded6d2cd79ddb75c2c36beab4802,PMC,Vimentin in Bacterial Infections,http://dx.doi.org/10.3390/cells5020018,PMC4931667,27096872,CC BY,"Despite well-studied bacterial strategies to target actin to subvert the host cell cytoskeleton, thus promoting bacterial survival, replication, and dissemination, relatively little is known about the bacterial interaction with other components of the host cell cytoskeleton, including intermediate filaments (IFs). IFs have not only roles in maintaining the structural integrity of the cell, but they are also involved in many cellular processes including cell adhesion, immune signaling, and autophagy, processes that are important in the context of bacterial infections. Here, we summarize the knowledge about the role of IFs in bacterial infections, focusing on the type III IF protein vimentin. Recent studies have revealed the involvement of vimentin in host cell defenses, acting as ligand for several pattern recognition receptors of the innate immune system. Two main aspects of bacteria-vimentin interactions are presented in this review: the role of vimentin in pathogen-binding on the cell surface and subsequent bacterial invasion and the interaction of cytosolic vimentin and intracellular pathogens with regards to innate immune signaling. Mechanistic insight is presented involving distinct bacterial virulence factors that target vimentin to subvert its function in order to change the host cell fate in the course of a bacterial infection.",2016 Apr 18,"['Mak, Tim N.', 'Brüggemann, Holger']",Cells,,,True
a21f8d21e09607e555468d0ed155126daaeb37cd,PMC,First isolation of West Nile virus from a dromedary camel,http://dx.doi.org/10.1038/emi.2016.53,PMC4932647,27273223,CC BY,"Although antibodies against West Nile virus (WNV) have been detected in the sera of dromedaries in the Middle East, North Africa and Spain, no WNV has been isolated or amplified from dromedary or Bactrian camels. In this study, WNV was isolated from Vero cells inoculated with both nasal swab and pooled trachea/lung samples from a dromedary calf in Dubai. Complete-genome sequencing and phylogenetic analysis using the near-whole-genome polyprotein revealed that the virus belonged to lineage 1a. There was no clustering of the present WNV with other WNVs isolated in other parts of the Middle East. Within lineage 1a, the dromedary WNV occupied a unique position, although it was most closely related to other WNVs of cluster 2. Comparative analysis revealed that the putative E protein encoded by the genome possessed the original WNV E protein glycosylation motif NYS at E154–156, which contained the N-linked glycosylation site at N-154 associated with increased WNV pathogenicity and neuroinvasiveness. In the putative NS1 protein, the A70S substitution observed in other cluster 2 WNVs and P250, which has been implicated in neuroinvasiveness, were present. In addition, the foo motif in the putative NS2A protein, which has been implicated in neuroinvasiveness, was detected. Notably, the amino-acid residues at 14 positions in the present dromedary WNV genome differed from those in most of the closely related WNV strains in cluster 2 of lineage 1a, with the majority of these differences observed in the putative E and NS5 proteins. The present study is the first to demonstrate the isolation of WNV from dromedaries. This finding expands the possible reservoirs of WNV and sources of WNV infection.",2016 Jun 8,"['Joseph, Sunitha', 'Wernery, Ulrich', 'Teng, Jade LL', 'Wernery, Renate', 'Huang, Yi', 'Patteril, Nissy AG', 'Chan, Kwok-Hung', 'Elizabeth, Shyna K', 'Fan, Rachel YY', 'Lau, Susanna KP', 'Kinne, Jörg', 'Woo, Patrick CY']",Emerg Microbes Infect,,,True
bbf555548912f929c3413cf6ee3314f9783cbb18,PMC,"An outbreak of cutaneous anthrax in Yunnan, China",http://dx.doi.org/10.1038/emi.2016.65,PMC4932653,27329849,CC BY,,2016 Jun 22,"['Huang, Ying', 'Du, Yingrong', 'Wang, Yaling', 'Wang, Ning', 'Bai, Jinsong', 'Chen, Haiyun', 'He, Hua', 'Xu, Jun', 'Wu, Yan', 'Luo, Yun', 'Li, Xiaolong', 'Liang, Guodong']",Emerg Microbes Infect,,,True
ab4c508f4a6ff84276581ce0746b4a5768728d0f,PMC,Occurrence of canine parvovirus in dogs from Henan province of China in 2009–2014,http://dx.doi.org/10.1186/s12917-016-0753-1,PMC4932751,27377264,CC BY,"BACKGROUND: There is no information concerning the genotype of Canine parvovirus (CPV) currently circulating in Henan province, China. Therefore, the aim of the present study was to provide insights into the epidemiology and molecular characterization of CPV circulating in Henan province from 2009 to 2014. RESULTS: Nineteen thousand nine hundred seven dogs from pet hospitals in the cities of Luoyang, Anyang, Jiaozuo, Sanmenxia, Xinxiang, Zhengzhou in Henan province between 2009 and 2014 were investigated. Over the 6-year period, 1169 CPV-positive cases were identified and the morbidity of CPV infection ranged from 4.16 to 8.06 %, although morbidity was not significant (P > 0.05) between 2009 and 2014. Factors associated with morbidity included sampling season, dog age, breed, vaccination status, and sex. CPV co-infection with coccidium (10.00 %), canine distemper virus (4.79 %), hookworm (2.40 %), canine coronavirus (1.11 %), roundworm (1.03 %), tapeworm (0.17 %) and Babesia spp. (0.09 %) were observed. The new CPV-2a variant was more prevalent than the new CPV-2b variant in Henan province. CPV 2c was not observed in this study. CONCLUSIONS: The epidemiology of CPV infection and identification of the circulating genotypes in Henan province, China from 2009 to 2014 determined that the new CPV-2a variant was more prevalent.",2016 Jul 4,"['Zhao, Zhanqin', 'Liu, Huisheng', 'Ding, Ke', 'Peng, Chunping', 'Xue, Qiao', 'Yu, Zuhua', 'Xue, Yun']",BMC Vet Res,,,True
c8de62f6c2fb721f1a0e80c81b70438ec75a9702,PMC,"Clean energy benefits the climate, the economy and our health",http://dx.doi.org/10.2471/BLT.16.030716,PMC4933147,27429487,CC BY,"Jeffrey D Sachs tells Fiona Fleck why investing in renewable energy is good for our health, but why poor countries need more time to make the switch.",2016 Jul 1,,Bull World Health Organ,,,False
039ca723ee32358eb70a084eaee19e1b6adc3033,PMC,"Global epidemiology of avian influenza A(H5N1) virus infection in humans, 1997 – 2015: a systematic review",http://dx.doi.org/10.1016/S1473-3099(16)00153-5,PMC4933299,27211899,CC BY,"Avian influenza viruses A(H5N1) have caused a large number of typically severe human infections since the first human case was reported in 1997. However, there is a lack of comprehensive epidemiological analysis of global human cases of H5N1 from 1997-2015. Moreover, few studies have examined in detail the changing epidemiology of human H5N1 cases in Egypt, especially given the most recent outbreaks since November 2014 which have the highest number of cases ever reported globally over a similar period. Data on individual cases were collated from different sources using a systematic approach to describe the global epidemiology of 907 human H5N1 cases between May 1997 and April 2015. The number of affected countries rose between 2003 and 2008, with expansion from East and Southeast Asia, then to West Asia and Africa. Most cases (67.2%) occurred from December to March, and the overall case fatality risk was 53.5% (483/903) which varied across geographical regions. Although the incidence in Egypt has increased dramatically since November 2014, compared to the cases beforehand there were no significant differences in the fatality risk , history of exposure to poultry, history of human case contact, and time from onset to hospitalization in the recent cases.",2016 Jul 17,"['Lai, Shengjie', 'Qin, Ying', 'Cowling, Benjamin J.', 'Ren, Xiang', 'Wardrop, Nicola A.', 'Gilbert, Marius', 'Tsang, Tim K.', 'Wu, Peng', 'Feng, Luzhao', 'Jiang, Hui', 'Peng, Zhibin', 'Zheng, Jiandong', 'Liao, Qiaohong', 'Li, Sa', 'Horby, Peter W.', 'Farrar, Jeremy J.', 'Gao, George F.', 'Tatem, Andrew J.', 'Yu, Hongjie']",Lancet Infect Dis,,,True
ab70ed497469460f2ec13fcfe51611005fab867a,PMC,Acute systemic DNA damage in youth does not impair immune defense with aging,http://dx.doi.org/10.1111/acel.12478,PMC4933672,27072188,CC BY,"Aging‐related decline in immunity is believed to be the main driver behind decreased vaccine efficacy and reduced resistance to infections in older adults. Unrepaired DNA damage is known to precipitate cellular senescence, which was hypothesized to be the underlying cause of certain age‐related phenotypes. Consistent with this, some hallmarks of immune aging were more prevalent in individuals exposed to whole‐body irradiation (WBI), which leaves no anatomical repository of undamaged hematopoietic cells. To decisively test whether and to what extent WBI in youth will leave a mark on the immune system as it ages, we exposed young male C57BL/6 mice to sublethal WBI (0.5–4 Gy), mimicking human survivor exposure during nuclear catastrophe. We followed lymphocyte homeostasis thorough the lifespan, response to vaccination, and ability to resist lethal viral challenge in the old age. None of the irradiated groups showed significant differences compared with mock‐irradiated (0 Gy) animals for the parameters measured. Even the mice that received the highest dose of sublethal WBI in youth (4 Gy) exhibited equilibrated lymphocyte homeostasis, robust T‐ and B‐cell responses to live attenuated West Nile virus (WNV) vaccine and full survival following vaccination upon lethal WNV challenge. Therefore, a single dose of nonlethal WBI in youth, resulting in widespread DNA damage and repopulation stress in hematopoietic cells, leaves no significant trace of increased immune aging in a lethal vaccine challenge model.",2016 Aug 13,"['Pugh, Jason L.', 'Foster, Sarah A.', 'Sukhina, Alona S.', 'Petravic, Janka', 'Uhrlaub, Jennifer L.', 'Padilla‐Torres, Jose', 'Hayashi, Tomonori', 'Nakachi, Kei', 'Smithey, Megan J.', 'Nikolich‐Žugich, Janko']",Aging Cell,,,True
e7976bbd13a90d95e706215c8d42c629fc7d5b4d,PMC,Acute systemic DNA damage in youth does not impair immune defense with aging,http://dx.doi.org/10.1111/acel.12478,PMC4933672,27072188,CC BY,"Aging‐related decline in immunity is believed to be the main driver behind decreased vaccine efficacy and reduced resistance to infections in older adults. Unrepaired DNA damage is known to precipitate cellular senescence, which was hypothesized to be the underlying cause of certain age‐related phenotypes. Consistent with this, some hallmarks of immune aging were more prevalent in individuals exposed to whole‐body irradiation (WBI), which leaves no anatomical repository of undamaged hematopoietic cells. To decisively test whether and to what extent WBI in youth will leave a mark on the immune system as it ages, we exposed young male C57BL/6 mice to sublethal WBI (0.5–4 Gy), mimicking human survivor exposure during nuclear catastrophe. We followed lymphocyte homeostasis thorough the lifespan, response to vaccination, and ability to resist lethal viral challenge in the old age. None of the irradiated groups showed significant differences compared with mock‐irradiated (0 Gy) animals for the parameters measured. Even the mice that received the highest dose of sublethal WBI in youth (4 Gy) exhibited equilibrated lymphocyte homeostasis, robust T‐ and B‐cell responses to live attenuated West Nile virus (WNV) vaccine and full survival following vaccination upon lethal WNV challenge. Therefore, a single dose of nonlethal WBI in youth, resulting in widespread DNA damage and repopulation stress in hematopoietic cells, leaves no significant trace of increased immune aging in a lethal vaccine challenge model.",2016 Aug 13,"['Pugh, Jason L.', 'Foster, Sarah A.', 'Sukhina, Alona S.', 'Petravic, Janka', 'Uhrlaub, Jennifer L.', 'Padilla‐Torres, Jose', 'Hayashi, Tomonori', 'Nakachi, Kei', 'Smithey, Megan J.', 'Nikolich‐Žugich, Janko']",Aging Cell,,,False
b8a55c284d17093b3d9c033f5c74633f47aaabe3,PMC,"The IRIDICA BAC BSI Assay: Rapid, Sensitive and Culture-Independent Identification of Bacteria and Candida in Blood",http://dx.doi.org/10.1371/journal.pone.0158186,PMC4934770,27384540,CC BY,"Bloodstream infection (BSI) and sepsis are rising in incidence throughout the developed world. The spread of multi-drug resistant organisms presents increasing challenges to treatment. Surviving BSI is dependent on rapid and accurate identification of causal organisms, and timely application of appropriate antibiotics. Current culture-based methods used to detect and identify agents of BSI are often too slow to impact early therapy and may fail to detect relevant organisms in many positive cases. Existing methods for direct molecular detection of microbial DNA in blood are limited in either sensitivity (likely the result of small sample volumes) or in breadth of coverage, often because the PCR primers and probes used target only a few specific pathogens. There is a clear unmet need for a sensitive molecular assay capable of identifying the diverse bacteria and yeast associated with BSI directly from uncultured whole blood samples. We have developed a method of extracting DNA from larger volumes of whole blood (5 ml per sample), amplifying multiple widely conserved bacterial and fungal genes using a mismatch- and background-tolerant PCR chemistry, and identifying hundreds of diverse organisms from the amplified fragments on the basis of species-specific genetic signatures using electrospray ionization mass spectrometry (PCR/ESI-MS). We describe the analytical characteristics of the IRIDICA BAC BSI Assay and compare its pre-clinical performance to current standard-of-care methods in a collection of prospectively collected blood specimens from patients with symptoms of sepsis. The assay generated matching results in 80% of culture-positive cases (86% when common contaminants were excluded from the analysis), and twice the total number of positive detections. The described method is capable of providing organism identifications directly from uncultured blood in less than 8 hours. Disclaimer: The IRIDICA BAC BSI Assay is not available in the United States.",2016 Jul 6,"['Metzgar, David', 'Frinder, Mark W.', 'Rothman, Richard E.', 'Peterson, Stephen', 'Carroll, Karen C.', 'Zhang, Sean X.', 'Avornu, Gideon D.', 'Rounds, Megan A.', 'Carolan, Heather E.', 'Toleno, Donna M.', 'Moore, David', 'Hall, Thomas A.', 'Massire, Christian', 'Richmond, Gregory S.', 'Gutierrez, Jose R.', 'Sampath, Rangarajan', 'Ecker, David J.', 'Blyn, Lawrence B.']",PLoS One,,,True
7146a5eb303bef6ef7c4bc2588a0305fc7b58cd3,PMC,Illuminating the Sites of Enterovirus Replication in Living Cells by Using a Split-GFP-Tagged Viral Protein,http://dx.doi.org/10.1128/mSphere.00104-16,PMC4935779,27390781,CC BY,"Like all other positive-strand RNA viruses, enteroviruses generate new organelles (replication organelles [ROs]) with a unique protein and lipid composition on which they multiply their viral genome. Suitable tools for live-cell imaging of enterovirus ROs are currently unavailable, as recombinant enteroviruses that carry genes that encode RO-anchored viral proteins tagged with fluorescent reporters have not been reported thus far. To overcome this limitation, we used a split green fluorescent protein (split-GFP) system, comprising a large fragment [strands 1 to 10; GFP(S1-10)] and a small fragment [strand 11; GFP(S11)] of only 16 residues. The GFP(S11) (GFP with S11 fragment) fragment was inserted into the 3A protein of the enterovirus coxsackievirus B3 (CVB3), while the large fragment was supplied by transient or stable expression in cells. The introduction of GFP(S11) did not affect the known functions of 3A when expressed in isolation. Using correlative light electron microscopy (CLEM), we showed that GFP fluorescence was detected at ROs, whose morphologies are essentially identical to those previously observed for wild-type CVB3, indicating that GFP(S11)-tagged 3A proteins assemble with GFP(S1-10) to form GFP for illumination of bona fide ROs. It is well established that enterovirus infection leads to Golgi disintegration. Through live-cell imaging of infected cells expressing an mCherry-tagged Golgi marker, we monitored RO development and revealed the dynamics of Golgi disassembly in real time. Having demonstrated the suitability of this virus for imaging ROs, we constructed a CVB3 encoding GFP(S1-10) and GFP(S11)-tagged 3A to bypass the need to express GFP(S1-10) prior to infection. These tools will have multiple applications in future studies on the origin, location, and function of enterovirus ROs. IMPORTANCE Enteroviruses induce the formation of membranous structures (replication organelles [ROs]) with a unique protein and lipid composition specialized for genome replication. Electron microscopy has revealed the morphology of enterovirus ROs, and immunofluorescence studies have been conducted to investigate their origin and formation. Yet, immunofluorescence analysis of fixed cells results in a rather static view of RO formation, and the results may be compromised by immunolabeling artifacts. While live-cell imaging of ROs would be preferred, enteroviruses encoding a membrane-anchored viral protein fused to a large fluorescent reporter have thus far not been described. Here, we tackled this constraint by introducing a small tag from a split-GFP system into an RO-resident enterovirus protein. This new tool bridges a methodological gap by circumventing the need for immunolabeling fixed cells and allows the study of the dynamics and formation of enterovirus ROs in living cells.",2016 Jul 6,"['van der Schaar, H. M.', 'Melia, C. E.', 'van Bruggen, J. A. C.', 'Strating, J. R. P. M.', 'van Geenen, M. E. D.', 'Koster, A. J.', 'Bárcena, M.', 'van Kuppeveld, F. J. M.']",mSphere,,,True
6ff089187feaca34bce964cc052bd1fa0f016d40,PMC,Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury,http://dx.doi.org/10.1155/2016/9476020,PMC4935915,27418745,CC BY,"Spinal cord injury results in a life-disrupting series of deleterious interconnected mechanisms encompassed by the primary and secondary injury. These events are mediated by the upregulation of genes with roles in inflammation, transcription, and signaling proteins. In particular, cytokines and growth factors are signaling proteins that have important roles in the pathophysiology of SCI. The balance between the proinflammatory and anti-inflammatory effects of these molecules plays a critical role in the progression and outcome of the lesion. The excessive inflammatory Th1 and Th17 phenotypes observed after SCI tilt the scale towards a proinflammatory environment, which exacerbates the deleterious mechanisms present after the injury. These mechanisms include the disruption of the spinal cord blood barrier, edema and ion imbalance, in particular intracellular calcium and sodium concentrations, glutamate excitotoxicity, free radicals, and the inflammatory response contributing to the neurodegenerative process which is characterized by demyelination and apoptosis of neuronal tissue.",2016 Jun 23,"['Garcia, Elisa', 'Aguilar-Cevallos, Jorge', 'Silva-Garcia, Raul', 'Ibarra, Antonio']",Mediators Inflamm,,,True
3d9b665ff94e800c03f3051567312a3921a76e81,PMC,Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters,http://dx.doi.org/10.1128/JVI.00304-16,PMC4936146,27099308,CC BY,"Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, dysregulation of components of the immune response is often suggested as a possible cause. Alveolar macrophages are found in the alveoli of the lung and represent the first line of defense to many airborne pathogens. To determine whether alveolar macrophages play a role in HPS pathogenesis, alveolar macrophages were depleted in an adult rodent model of HPS that closely resembles human HPS. Syrian hamsters were treated, intratracheally, with clodronate-encapsulated liposomes or control liposomes and were then challenged with ANDV. Treatment with clodronate-encapsulated liposomes resulted in significant reduction in alveolar macrophages, but depletion did not prevent pathogenesis or prolong disease. Depletion also did not significantly reduce the amount of virus in the lung of ANDV-infected hamsters but altered neutrophil recruitment, MIP-1α and MIP-2 chemokine expression, and vascular endothelial growth factor (VEGF) levels in hamster bronchoalveolar lavage (BAL) fluid early after intranasal challenge. These data demonstrate that alveolar macrophages may play a limited protective role early after exposure to aerosolized ANDV but do not directly contribute to hantavirus disease pathogenesis in the hamster model of HPS. IMPORTANCE Hantaviruses continue to cause disease worldwide for which there are no FDA-licensed vaccines, effective postexposure prophylactics, or therapeutics. Much of this can be attributed to a poor understanding of the mechanism of hantavirus disease pathogenesis. Hantavirus disease has long been considered an immune-mediated disease; however, by directly manipulating the Syrian hamster model, we continue to eliminate individual immune cell types. As the most numerous immune cells present in the respiratory tract, alveolar macrophages are poised to defend against hantavirus infection, but those antiviral responses may also contribute to hantavirus disease. Here, we demonstrate that, like in our prior T and B cell studies, alveolar macrophages neither prevent hantavirus infection nor cause hantavirus disease. While these studies reflect pathogenesis in the hamster model, they should help us rule out specific cell types and prompt us to consider other potential mechanisms of disease in an effort to improve the outcome of human HPS.",2016 Jun 24,"['Hammerbeck, Christopher D.', 'Brocato, Rebecca L.', 'Bell, Todd M.', 'Schellhase, Christopher W.', 'Mraz, Steven R.', 'Queen, Laurie A.', 'Hooper, Jay W.']",J Virol,,,True
6fb5ec70b6d25243856c076c05809c2ed9d49bf1,PMC,A novel role for poly(C) binding proteins in programmed ribosomal frameshifting,http://dx.doi.org/10.1093/nar/gkw480,PMC4937337,27257056,CC BY,"Translational control through programmed ribosomal frameshifting (PRF) is exploited widely by viruses and increasingly documented in cellular genes. Frameshifting is induced by mRNA secondary structures that compromise ribosome fidelity during decoding of a heptanucleotide ‘slippery’ sequence. The nsp2 PRF signal of porcine reproductive and respiratory syndrome virus is distinctive in directing both −2 and −1 PRF and in its requirement for a trans-acting protein factor, the viral replicase subunit nsp1β. Here we show that the the trans-activation of frameshifting is carried out by a protein complex composed of nsp1β and a cellular poly(C) binding protein (PCBP). From the results of in vitro translation and electrophoretic mobility shift assays, we demonstrate that a PCBP/nsp1β complex binds to a C-rich sequence downstream of the slippery sequence and here mimics the activity of a structured mRNA stimulator of PRF. This is the first description of a role for a trans-acting cellular protein in PRF. The discovery broadens the repertoire of activities associated with poly(C) binding proteins and prototypes a new class of virus–host interactions.",2016 Jul 8,"['Napthine, Sawsan', 'Treffers, Emmely E.', 'Bell, Susanne', 'Goodfellow, Ian', 'Fang, Ying', 'Firth, Andrew E.', 'Snijder, Eric J.', 'Brierley, Ian']",Nucleic Acids Res,,,True
dcd1759241f327b5235520cebe1f7432aa936c5d,PMC,A novel role for poly(C) binding proteins in programmed ribosomal frameshifting,http://dx.doi.org/10.1093/nar/gkw480,PMC4937337,27257056,CC BY,"Translational control through programmed ribosomal frameshifting (PRF) is exploited widely by viruses and increasingly documented in cellular genes. Frameshifting is induced by mRNA secondary structures that compromise ribosome fidelity during decoding of a heptanucleotide ‘slippery’ sequence. The nsp2 PRF signal of porcine reproductive and respiratory syndrome virus is distinctive in directing both −2 and −1 PRF and in its requirement for a trans-acting protein factor, the viral replicase subunit nsp1β. Here we show that the the trans-activation of frameshifting is carried out by a protein complex composed of nsp1β and a cellular poly(C) binding protein (PCBP). From the results of in vitro translation and electrophoretic mobility shift assays, we demonstrate that a PCBP/nsp1β complex binds to a C-rich sequence downstream of the slippery sequence and here mimics the activity of a structured mRNA stimulator of PRF. This is the first description of a role for a trans-acting cellular protein in PRF. The discovery broadens the repertoire of activities associated with poly(C) binding proteins and prototypes a new class of virus–host interactions.",2016 Jul 8,"['Napthine, Sawsan', 'Treffers, Emmely E.', 'Bell, Susanne', 'Goodfellow, Ian', 'Fang, Ying', 'Firth, Andrew E.', 'Snijder, Eric J.', 'Brierley, Ian']",Nucleic Acids Res,,,True
2e50303039d019b3f817743da8a21e60f3b99130,PMC,"Two Multiplex Real-Time PCR Assays to Detect and Differentiate Acinetobacter baumannii and Non- baumannii Acinetobacter spp. Carrying bla(NDM), bla(OXA-23-Like), bla(OXA-40-Like), bla(OXA-51-Like), and bla(OXA-58-Like) Genes",http://dx.doi.org/10.1371/journal.pone.0158958,PMC4938629,27391234,CC BY,"Nosocomial infections caused by Acinetobacter spp. resistant to carbapenems are increasingly reported worldwide. Carbapenem-resistant Acinetobacter (CRA) is becoming a serious concern with increasing patient morbidity, mortality, and lengths of hospital stay. Therefore, the rapid detection of CRA is essential for epidemiological surveillance. Polymerase chain reaction (PCR) has been extensively used for the rapid identification of most pathogens. In this study, we have developed two multiplex real-time PCR assays to detect and differentiate A. baumannii and non-A. baumannii Acinetobacter spp, and common carbapenemase genes, including bla(NDM), bla(OXA-23-like), bla(OXA-40-like), bla(OXA-51-like), and bla(OXA-58-like). We demonstrate the potential utility of these assays for the direct detection of bla(NDM)-, bla(OXA-23-like)-, bla(OXA-40-like)-, bla(OXA-51-like)-, and bla(OXA-58-like)-positive CRA in clinical specimens. Primers were specifically designed, and two multiplex real-time PCR assays were developed: multiplex real-time PCR assay1 for the detection of Acinetobacter baumannii 16S–23S rRNA internal transcribed spacer sequence, the Acinetobacter recA gene, and class-B-metalloenzyme-encoding gene bla(NDM); and multiplex real-time PCR assay2 to detect class-D-oxacillinase-encoding genes (bla(OXA-23-like), bla(OXA-40-like), bla(OXA-51-like),and bla(OXA-58-like)). The assays were performed on an ABI Prism 7500 FAST Real-Time PCR System. CRA isolates were used to compare the assays with conventional PCR and sequencing. Known amounts of CRA cells were added to sputum and fecal specimens and used to test the multiplex real-time PCR assays. The results for target and nontarget amplification showed that the multiplex real-time PCR assays were specific, the limit of detection for each target was 10 copies per 20 μL reaction volume, the assays were linear over six log dilutions of the target genes (r(2) > 0.99), and the Ct values of the coefficients of variation for intra- and interassay reproducibility were less than 5%. The multiplex real-time PCR assays showed 100% concordance with conventional PCR when tested against 400 CRA isolates and their sensitivity for the target DNA in sputum and fecal specimens was 10(2) CFU/mL. Therefore, these novel multiplex real-time PCR assays allow the sensitive and specific characterization and differentiation of bla(NDM)-, bla(OXA-23-like)-, bla(OXA-40-like)-, bla(OXA-51-like)-, and bla(OXA-58-like)-positive CRA, making them potential tools for the direct detection of CRA in clinical specimens and the surveillance of nosocomial infections.",2016 Jul 8,"['Yang, Qiu', 'Rui, Yongyu']",PLoS One,,,True
48ac03386c65d4912b6455b123bde25f6e48f68c,PMC,Association of sputum microbiota profiles with severity of community-acquired pneumonia in children,http://dx.doi.org/10.1186/s12879-016-1670-4,PMC4939047,27391033,CC BY,"BACKGROUND: Competitive interactions among bacteria in the respiratory tract microbiota influence which species can colonize and potentially contribute to pathogenesis of community-acquired pneumonia (CAP). However, understanding of the role of respiratory tract microbiota in the clinical course of pediatric CAP is limited. METHODS: We sought to compare microbiota profiles in induced sputum and nasopharyngeal/oropharyngeal (NP/OP) samples from children and to identify microbiota profiles associated with CAP severity. We used 16S ribosomal RNA sequencing and several measures of microbiota profiles, including principal component analysis (PCA), to describe the respiratory microbiota in 383 children, 6 months to <18 years, hospitalized with CAP. We examined associations between induced sputum and NP/OP microbiota profiles and CAP severity (hospital length of stay and intensive care unit admission) using logistic regression. RESULTS: Relative abundance of bacterial taxa differed in induced sputum and NP/OP samples. In children 6 months to < 5 years, the sputum PCA factor with high relative abundance of Actinomyces, Veillonella, Rothia, and Lactobacillales was associated with decreased odds of length of stay ≥ 4 days [adjusted odds ratio (aOR) 0.69; 95 % confidence interval (CI) 0.48–0.99]. The sputum factor with high relative abundance of Haemophilus and Pasteurellaceae was associated with increased odds of intensive care unit admission [aOR 1.52; 95 % CI 1.02–2.26]. In children 5 to < 18 years, the sputum factor with high relative abundance of Porphyromonadaceae, Bacteriodales, Lactobacillales, and Prevotella was associated with increased odds of length of stay ≥ 4 days [aOR 1.52; 95 % CI 1.02–2.26]. Taxa in NP/OP samples were not associated with CAP severity. CONCLUSION: Certain taxa in the respiratory microbiota, which were detected in induced sputum samples, are associated with the clinical course of CAP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1670-4) contains supplementary material, which is available to authorized users.",2016 Jul 8,"['Pettigrew, Melinda M.', 'Gent, Janneane F.', 'Kong, Yong', 'Wade, Martina', 'Gansebom, Shane', 'Bramley, Anna M.', 'Jain, Seema', 'Arnold, Sandra L. R.', 'McCullers, Jonathan A.']",BMC Infect Dis,,,False
91faf9aa02611ff7e20a3c45babd11cdf0611a2b,PMC,Association of sputum microbiota profiles with severity of community-acquired pneumonia in children,http://dx.doi.org/10.1186/s12879-016-1670-4,PMC4939047,27391033,CC BY,"BACKGROUND: Competitive interactions among bacteria in the respiratory tract microbiota influence which species can colonize and potentially contribute to pathogenesis of community-acquired pneumonia (CAP). However, understanding of the role of respiratory tract microbiota in the clinical course of pediatric CAP is limited. METHODS: We sought to compare microbiota profiles in induced sputum and nasopharyngeal/oropharyngeal (NP/OP) samples from children and to identify microbiota profiles associated with CAP severity. We used 16S ribosomal RNA sequencing and several measures of microbiota profiles, including principal component analysis (PCA), to describe the respiratory microbiota in 383 children, 6 months to <18 years, hospitalized with CAP. We examined associations between induced sputum and NP/OP microbiota profiles and CAP severity (hospital length of stay and intensive care unit admission) using logistic regression. RESULTS: Relative abundance of bacterial taxa differed in induced sputum and NP/OP samples. In children 6 months to < 5 years, the sputum PCA factor with high relative abundance of Actinomyces, Veillonella, Rothia, and Lactobacillales was associated with decreased odds of length of stay ≥ 4 days [adjusted odds ratio (aOR) 0.69; 95 % confidence interval (CI) 0.48–0.99]. The sputum factor with high relative abundance of Haemophilus and Pasteurellaceae was associated with increased odds of intensive care unit admission [aOR 1.52; 95 % CI 1.02–2.26]. In children 5 to < 18 years, the sputum factor with high relative abundance of Porphyromonadaceae, Bacteriodales, Lactobacillales, and Prevotella was associated with increased odds of length of stay ≥ 4 days [aOR 1.52; 95 % CI 1.02–2.26]. Taxa in NP/OP samples were not associated with CAP severity. CONCLUSION: Certain taxa in the respiratory microbiota, which were detected in induced sputum samples, are associated with the clinical course of CAP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1670-4) contains supplementary material, which is available to authorized users.",2016 Jul 8,"['Pettigrew, Melinda M.', 'Gent, Janneane F.', 'Kong, Yong', 'Wade, Martina', 'Gansebom, Shane', 'Bramley, Anna M.', 'Jain, Seema', 'Arnold, Sandra L. R.', 'McCullers, Jonathan A.']",BMC Infect Dis,,,False
18d6b41f2b9f5cad93519eb39f422f7f008a4ed3,PMC,Association of sputum microbiota profiles with severity of community-acquired pneumonia in children,http://dx.doi.org/10.1186/s12879-016-1670-4,PMC4939047,27391033,CC BY,"BACKGROUND: Competitive interactions among bacteria in the respiratory tract microbiota influence which species can colonize and potentially contribute to pathogenesis of community-acquired pneumonia (CAP). However, understanding of the role of respiratory tract microbiota in the clinical course of pediatric CAP is limited. METHODS: We sought to compare microbiota profiles in induced sputum and nasopharyngeal/oropharyngeal (NP/OP) samples from children and to identify microbiota profiles associated with CAP severity. We used 16S ribosomal RNA sequencing and several measures of microbiota profiles, including principal component analysis (PCA), to describe the respiratory microbiota in 383 children, 6 months to <18 years, hospitalized with CAP. We examined associations between induced sputum and NP/OP microbiota profiles and CAP severity (hospital length of stay and intensive care unit admission) using logistic regression. RESULTS: Relative abundance of bacterial taxa differed in induced sputum and NP/OP samples. In children 6 months to < 5 years, the sputum PCA factor with high relative abundance of Actinomyces, Veillonella, Rothia, and Lactobacillales was associated with decreased odds of length of stay ≥ 4 days [adjusted odds ratio (aOR) 0.69; 95 % confidence interval (CI) 0.48–0.99]. The sputum factor with high relative abundance of Haemophilus and Pasteurellaceae was associated with increased odds of intensive care unit admission [aOR 1.52; 95 % CI 1.02–2.26]. In children 5 to < 18 years, the sputum factor with high relative abundance of Porphyromonadaceae, Bacteriodales, Lactobacillales, and Prevotella was associated with increased odds of length of stay ≥ 4 days [aOR 1.52; 95 % CI 1.02–2.26]. Taxa in NP/OP samples were not associated with CAP severity. CONCLUSION: Certain taxa in the respiratory microbiota, which were detected in induced sputum samples, are associated with the clinical course of CAP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1670-4) contains supplementary material, which is available to authorized users.",2016 Jul 8,"['Pettigrew, Melinda M.', 'Gent, Janneane F.', 'Kong, Yong', 'Wade, Martina', 'Gansebom, Shane', 'Bramley, Anna M.', 'Jain, Seema', 'Arnold, Sandra L. R.', 'McCullers, Jonathan A.']",BMC Infect Dis,,,True
6908a089fea0a7345e066dfd10462507601d88eb,PMC,"Complete Genome Sequence of Porcine Epidemic Diarrhea Virus from an Outbreak in a Vaccinated Farm in Shandong, China",http://dx.doi.org/10.1128/genomeA.00619-16,PMC4939784,27389267,CC BY,"Porcine epidemic diarrhea virus, a member of the family Coronaviridae, is an economically important pathogen that causes severe enteritis, vomiting, dehydration, and a high mortality rate, especially among suckling piglets. Here, we report the complete genome sequence (28,036 nucleotides [nt]) of a porcine epidemic diarrhea virus (PEDV) strain isolated in a novel outbreak in Shandong, China.",2016 Jul 7,"['Gao, Xiang', 'Li, Dongliang', 'Zhao, Jingyi', 'Xu, Farong', 'Ge, Xinna', 'Guo, Xin', 'Han, Jun', 'Yang, Hanchun', 'Zhou, Lei']",Genome Announc,,,True
714e40f88f6e629f0f63574ec52ea967aeee4065,PMC,Cryo-electron Microscopy Structure of the Native Prototype Foamy Virus Glycoprotein and Virus Architecture,http://dx.doi.org/10.1371/journal.ppat.1005721,PMC4939959,27399201,CC BY,"Foamy viruses (FV) belong to the genus Spumavirus, which forms a distinct lineage in the Retroviridae family. Although the infection in natural hosts and zoonotic transmission to humans is asymptomatic, FVs can replicate well in human cells making it an attractive gene therapy vector candidate. Here we present cryo-electron microscopy and (cryo-)electron tomography ultrastructural data on purified prototype FV (PFV) and PFV infected cells. Mature PFV particles have a distinct morphology with a capsid of constant dimension as well as a less ordered shell of density between the capsid and the membrane likely formed by the Gag N-terminal domain and the cytoplasmic part of the Env leader peptide gp18(LP). The viral membrane contains trimeric Env glycoproteins partly arranged in interlocked hexagonal assemblies. In situ 3D reconstruction by subtomogram averaging of wild type Env and of a Env gp48(TM)- gp80(SU) cleavage site mutant showed a similar spike architecture as well as stabilization of the hexagonal lattice by clear connections between lower densities of neighboring trimers. Cryo-EM was employed to obtain a 9 Å resolution map of the glycoprotein in its pre-fusion state, which revealed extensive trimer interactions by the receptor binding subunit gp80(SU) at the top of the spike and three central helices derived from the fusion protein subunit gp48(TM). The lower part of Env, presumably composed of interlaced parts of gp48(TM), gp80(SU) and gp18(LP) anchors the spike at the membrane. We propose that the gp48(TM) density continues into three central transmembrane helices, which interact with three outer transmembrane helices derived from gp18(LP). Our ultrastructural data and 9 Å resolution glycoprotein structure provide important new insights into the molecular architecture of PFV and its distinct evolutionary relationship with other members of the Retroviridae.",2016 Jul 11,"['Effantin, Grégory', 'Estrozi, Leandro F.', 'Aschman, Nick', 'Renesto, Patricia', 'Stanke, Nicole', 'Lindemann, Dirk', 'Schoehn, Guy', 'Weissenhorn, Winfried']",PLoS Pathog,,,True
84bb5b317c837c22b090bc10357a3542f58402bd,PMC,Genetic characterization of commensal Escherichia coli isolated from laboratory rodents,http://dx.doi.org/10.1186/s40064-016-2745-9,PMC4940358,27462483,CC BY,"BACKGROUND: Escherichia coli, a commensal in the intestines of vertebrates, is capable of colonizing many different hosts and the environment. Commensal E. coli strains are believed to be the precursor of pathogenic strains by means of acquisition of antimicrobial resistant and virulence genes. Laboratory rodents are inherently susceptible to numerous known infectious agents, which could transfer virulence determinants to commensal E. coli. Hence, in this study, the genetic structure of commensal E. coli found in laboratory rodents and their antimicrobial resistance profiles were investigated. RESULTS: E. coli strains belonging to phylogroup A were the predominant strain obtained from the animals used in the study. Four novel sequence types (ST746, ST747, ST748 and ST749) were discovered using the multi locus sequence typing, together with one common ST357 in the gastrointestinal tract, liver and, the trachea and lung. Serotyping demonstrated that these commensal E. coli strains were non-Shiga toxin-producers. Phenotypic and genotypic analyses of extended spectrum beta lactamases were also negative. CONCLUSIONS: These findings implied that the E. coli strains recovered from the laboratory rodents were truly commensal in nature. Further study is required to investigate the possible influence of gender on the susceptibility of hosts to E. coli colonization in laboratory rodents. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-016-2745-9) contains supplementary material, which is available to authorized users.",2016 Jul 11,"['Loong, Shih Keng', 'Mahfodz, Nur Hidayana', 'Che Mat Seri, Nurul Asma Anati', 'Mohamad Wali, Haryanti Azura', 'Abd Gani, Syahar Amir', 'Wong, Pooi-Fong', 'AbuBakar, Sazaly']",Springerplus,,,True
4a8a6f65da6c9eca4117de59c6377a0ff02a0d09,PMC,"Efficacy, Safety, and Pharmacokinetics of a New 10 % Liquid Intravenous Immunoglobulin Containing High Titer Neutralizing Antibody to RSV and Other Respiratory Viruses in Subjects with Primary Immunodeficiency Disease",http://dx.doi.org/10.1007/s10875-016-0308-z,PMC4940435,27324887,CC BY,"PURPOSE: Immune globulins for IgG supplementation have been produced for over 35 years with essentially no differentiating features regarding their specific antibody composition. Furthermore, the compositions of plasma donor pools used for IG manufacturing are not standardized. While all immune globulin products meet the specifications set by the US FDA for antibodies to pathogens like measles and polio, they have variable levels of antibodies to other important viruses and infectious pathogens, particularly respiratory syncytial virus (RSV). METHODS: An IVIG was developed that satisfies the requirements for treating patients with primary immune deficiency disease (PIDD) and also has standardized elevated levels of RSV neutralizing antibodies (RI-002). Plasma donors who have naturally occurring high circulating levels of neutralizing anti-RSV antibody were selected as the source for manufacturing IVIG to treat patients with PIDD to prevent serious bacterial infections. While the introduction of the monoclonal antibody Palivizumab has had a dramatic impact in diminishing the burden of RSV disease in the pediatric population, it does not meet the standards for replacing the deficient immune compartments of patients with PIDD. RESULTS: Fifty-nine patients with PIDD at 9 different sites across the US were enrolled in this study and received regular infusions of RI-002 over the course of 1 year. CONCLUSIONS: There were zero serious bacterial infections, thus meeting the primary endpoint for this trial. The secondary endpoints including days missed from work due to infection, unscheduled visits to the physician, and days of hospitalization due to infection compared favorably to published reports of other IVIG products.",2016 Jun 20,"['Wasserman, Richard L.', 'Lumry, William', 'Harris, James', 'Levy, Robyn', 'Stein, Mark', 'Forbes, Lisa', 'Cunningham-Rundles, Charlotte', 'Melamed, Isaac', 'Kobayashi, Ai Lan', 'Du, Wei', 'Kobayashi, Roger']",J Clin Immunol,,,True
4fcb098e746e236ebc700fc79262c3263550b3d9,PMC,Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches,http://dx.doi.org/10.1038/srep29680,PMC4940736,27403722,CC BY,"The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development.",2016 Jul 12,"['Fu, Xu', 'Wang, Zhihua', 'Li, Lixin', 'Dong, Shishang', 'Li, Zhucui', 'Jiang, Zhenzuo', 'Wang, Yuefei', 'Shui, Wenqing']",Sci Rep,,,True
370500e606926d13ff711d404ee1d7cafa6c3c1c,PMC,Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches,http://dx.doi.org/10.1038/srep29680,PMC4940736,27403722,CC BY,"The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development.",2016 Jul 12,"['Fu, Xu', 'Wang, Zhihua', 'Li, Lixin', 'Dong, Shishang', 'Li, Zhucui', 'Jiang, Zhenzuo', 'Wang, Yuefei', 'Shui, Wenqing']",Sci Rep,,,False
b314e4a20b1f0a2f4a49afb65c17859ad7d50c4d,PMC,CCR5 knockout suppresses experimental autoimmune encephalomyelitis in C57BL/6 mice,http://dx.doi.org/10.18632/oncotarget.8097,PMC4941248,26985768,CC BY,"Multiple sclerosis (MS) is an inflammatory disease in which myelin in the spinal cord is damaged. C-C chemokine receptor type 5 (CCR5) is implicated in immune cell migration and cytokine release in central nervous system (CNS). We investigated whether CCR5 plays a role in MS progression using a murine model, experimental autoimmune encephalomyelitis (EAE), in CCR5 deficient (CCR5(−/−)) mice. CCR5(−/−) and CCR5(+/+) (wild-type) mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG(35-55)) followed by pertussis toxin, after which EAE paralysis was scored for 28 days. We found that clinical scoring and EAE neuropathology were lower in CCR5(−/−) mice than CCR5(+/+) mice. Immune cells (CD3(+), CD4(+), CD8(+), B cell, NK cell and macrophages) infiltration and astrocytes/microglial activation were attenuated in CCR5(−/−) mice. Moreover, levels of IL-1β, TNF-α, IFN-γ and MCP-1 cytokine levels were decreased in CCR5(−/−) mice spinal cord. Myelin basic protein (MBP) and CNPase were increased while NG2 and O4 were decreased in CCR5(−/−) mice, indicating that demyelination was suppressed by CCR5 gene deletion. These findings suggest that CCR5 is likely participating in demyelination in the spinal cord the MS development, and that it could serve as an effective therapeutic target for the treatment of MS.",2016 Mar 15,"['Gu, Sun Mi', 'Park, Mi Hee', 'Yun, Hyung Mun', 'Han, Sang Bae', 'Oh, Ki Wan', 'Son, Dong Ju', 'Yun, Jae Suk', 'Hong, Jin Tae']",Oncotarget,,,True
6f3dddc4c061491fb43651e9bb61039ac7594a78,PMC,CCR5 knockout suppresses experimental autoimmune encephalomyelitis in C57BL/6 mice,http://dx.doi.org/10.18632/oncotarget.8097,PMC4941248,26985768,CC BY,"Multiple sclerosis (MS) is an inflammatory disease in which myelin in the spinal cord is damaged. C-C chemokine receptor type 5 (CCR5) is implicated in immune cell migration and cytokine release in central nervous system (CNS). We investigated whether CCR5 plays a role in MS progression using a murine model, experimental autoimmune encephalomyelitis (EAE), in CCR5 deficient (CCR5(−/−)) mice. CCR5(−/−) and CCR5(+/+) (wild-type) mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG(35-55)) followed by pertussis toxin, after which EAE paralysis was scored for 28 days. We found that clinical scoring and EAE neuropathology were lower in CCR5(−/−) mice than CCR5(+/+) mice. Immune cells (CD3(+), CD4(+), CD8(+), B cell, NK cell and macrophages) infiltration and astrocytes/microglial activation were attenuated in CCR5(−/−) mice. Moreover, levels of IL-1β, TNF-α, IFN-γ and MCP-1 cytokine levels were decreased in CCR5(−/−) mice spinal cord. Myelin basic protein (MBP) and CNPase were increased while NG2 and O4 were decreased in CCR5(−/−) mice, indicating that demyelination was suppressed by CCR5 gene deletion. These findings suggest that CCR5 is likely participating in demyelination in the spinal cord the MS development, and that it could serve as an effective therapeutic target for the treatment of MS.",2016 Mar 15,"['Gu, Sun Mi', 'Park, Mi Hee', 'Yun, Hyung Mun', 'Han, Sang Bae', 'Oh, Ki Wan', 'Son, Dong Ju', 'Yun, Jae Suk', 'Hong, Jin Tae']",Oncotarget,,,False
109a7800d93fdf2a2c64a261aab1182dd5b607af,PMC,The pathogenesis of multifocal osteonecrosis,http://dx.doi.org/10.1038/srep29576,PMC4941719,27404962,CC BY,"Our objective was to study the incidence, etiology, and diagnosis of multifocal osteonecrosis (MFON) and its treatment options to facilitate an earlier diagnosis and to optimize treatment. A radiological investigation was performed in osteonecrosis patients with a high risk of MFON for a more accurate diagnosis between January 2010 and June 2015. For patients with osteonecrosis of both the hip and knee joints or for patients with a history of corticosteroid use or alcohol abuse who had osteonecrosis of one or more joints in the shoulder, ankle, wrist or elbow, magnetic resonance imaging (MRI) was also performed on other joints, regardless of whether these joints were symptomatic. Furthermore, we performed a radiological screening of 102 patients who had a negative diagnosis of MFON but were at a high risk; among them, another 31 MFON cases were successfully identified (30.4%). Thus, the incidence of MFON during the study period increased from 3.1% to 5.2%. Patients diagnosed with osteonecrosis and who are at a high risk of MFON should have their other joints radiologically examined when necessary. This will reduce missed diagnosis of MFON and facilitate an earlier diagnosis and treatment to achieve an optimal outcome.",2016 Jul 11,"['Sun, Wei', 'Shi, Zhencai', 'Gao, Fuqiang', 'Wang, Bailiang', 'Li, Zirong']",Sci Rep,,,True
31c0ee2b6dff1699d251316667c0b56c7b8f09a3,PMC,Host protective ASP-based vaccine against the parasitic nematode Ostertagia ostertagi triggers NK cell activation and mixed IgG1-IgG2 response,http://dx.doi.org/10.1038/srep29496,PMC4941725,27403891,CC BY,"The mucus-dwelling parasite Ostertagia ostertagi is one of the most important gastrointestinal nematodes in cattle. Our group has previously demonstrated the protective capacity of a vaccine against this parasite based on a native activation-associated secreted protein ASP1 (nASP) in combination with the saponin adjuvant QuilA. The aim of the current study was to analyse the effect of both antigen and adjuvant on the cellular and humoral vaccine-induced immune responses by comparing the native ASP to a recombinant version expressed in Pichia pastoris (pASP) and replacing QuilA by Al(OH)(3). Immunization of cattle with the protective nASP+QuilA vaccine was associated with antigen-induced proliferation of natural killer (NK) cells combined with IFN-γ secretion and the induction of a mixed IgG1/IgG2 antibody response. ASP-specific activation and proliferation of NK cells was also observed in mice following the same vaccination regime. Replacing QuilA by Al(OH)(3) or nASP by pASP significantly decreased the capacity of the vaccines to trigger both NK cell activation and antibody responses and failed to induce protection against a challenge infection. Reduction of the structurally anchoring disulphide bonds of the nASP completely abolished its ability to induce NK cell activation and antibody responses, highlighting the importance of protein conformation for the immunostimulatory activity.",2016 Jul 11,"['González-Hernández, Ana', 'Van Coppernolle, Stefanie', 'Borloo, Jimmy', 'Van Meulder, Frederik', 'Paerewijck, Oonagh', 'Peelaers, Iris', 'Leclercq, Georges', 'Claerebout, Edwin', 'Geldhof, Peter']",Sci Rep,,,True
eb8cabb9a02a33566499d48341169eb6aa291b47,PMC,Host protective ASP-based vaccine against the parasitic nematode Ostertagia ostertagi triggers NK cell activation and mixed IgG1-IgG2 response,http://dx.doi.org/10.1038/srep29496,PMC4941725,27403891,CC BY,"The mucus-dwelling parasite Ostertagia ostertagi is one of the most important gastrointestinal nematodes in cattle. Our group has previously demonstrated the protective capacity of a vaccine against this parasite based on a native activation-associated secreted protein ASP1 (nASP) in combination with the saponin adjuvant QuilA. The aim of the current study was to analyse the effect of both antigen and adjuvant on the cellular and humoral vaccine-induced immune responses by comparing the native ASP to a recombinant version expressed in Pichia pastoris (pASP) and replacing QuilA by Al(OH)(3). Immunization of cattle with the protective nASP+QuilA vaccine was associated with antigen-induced proliferation of natural killer (NK) cells combined with IFN-γ secretion and the induction of a mixed IgG1/IgG2 antibody response. ASP-specific activation and proliferation of NK cells was also observed in mice following the same vaccination regime. Replacing QuilA by Al(OH)(3) or nASP by pASP significantly decreased the capacity of the vaccines to trigger both NK cell activation and antibody responses and failed to induce protection against a challenge infection. Reduction of the structurally anchoring disulphide bonds of the nASP completely abolished its ability to induce NK cell activation and antibody responses, highlighting the importance of protein conformation for the immunostimulatory activity.",2016 Jul 11,"['González-Hernández, Ana', 'Van Coppernolle, Stefanie', 'Borloo, Jimmy', 'Van Meulder, Frederik', 'Paerewijck, Oonagh', 'Peelaers, Iris', 'Leclercq, Georges', 'Claerebout, Edwin', 'Geldhof, Peter']",Sci Rep,,,False
2618f1868d3eaf92f7f306467b9c8d91ec7572ba,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,True
7e631e260a55ab4d59f63b26e52751a887b43749,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
9d2d67ed3a51962962399189441bf8e56b1c8f05,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
013e59d78b56b934b608e1ab2af766f6cbf5767c,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
3cf75eb0fab0b107484f83f5d2bde3a7100f9b9e,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
1058752cdbce833369e36bd54533bd5877b298eb,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
17c2c7b70fdaa3c6c0458580631056cf502b1b2b,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
2c8f174dd3e9c36ae7f49f4fcbf25b36b89f3d6e,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
fab4063e3f79d8f35d31cd5a26a93d0cbcd57186,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
6ee96231a86e71b65721eb972d03ef12dcbd5251,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
5e82264bcbfc8321618fa3d4b8d1c5cf165c2e93,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
d28644b207846776f4a9c6829a5167b0371797bd,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
efb13e65adfd16cd39afcea3dde4b0a83a26ad53,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
e881ac8842076e240f5a8612630f099d8e273e05,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
63f2edb69f2f971520167144c280cb6d70f0f884,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
819b587f7250e5bb2470826cfb87ad311aab711e,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
036f6cd2baef44fb73ab5664e3a1211f2b8c2f1c,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
cb7351d6e0190d59cb0bd93ddbdebbe10c6d4958,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
c815c7fc324a6ac8e11e6c7eba2289e7fb368728,PMC,Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens,http://dx.doi.org/10.1371/journal.pcbi.1005013,PMC4942116,27403523,CC BY,"Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.",2016 Jul 12,"['Chasman, Deborah', 'Walters, Kevin B.', 'Lopes, Tiago J. S.', 'Eisfeld, Amie J.', 'Kawaoka, Yoshihiro', 'Roy, Sushmita']",PLoS Comput Biol,,,False
a51659a324f74a7cf16acd3b1180d203cab2b8d4,PMC,Profiling of Host Cell Response to Successive Canine Parvovirus Infection Based on Kinetic Proteomic Change Identification,http://dx.doi.org/10.1038/srep29560,PMC4942776,27406444,CC BY,"Canine parvovirus (CPV) reproduces by co-opting the resources of host cells, inevitably causing cytotoxic effects to the host cells. Feline kidney F81 cells are sensitive to CPV infection and show disparate growing statuses at different time points post-infection. This study analysed the response of F81 cells to CPV infection at successive infection time points by iTRAQ-based quantitative proteomics. Differentially expressed proteins (DEPs) during 60 h of infection and at selected time points post-infection were identified by an analysis of variance test and a two-tailed unpaired t test, respectively. DEPs with similar quantitative changes were clustered by hierarchical clustering and analysed by gene ontology enrichment, revealing that 12 h and 60 h post-infection were the optimal times to analyse the autonomous parvovirus replication and apoptosis processes, respectively. Using the Metacore(TM) database, 29 DEPs were enriched in a network involved in p53 regulation. Besides, a significantly enriched pathway suggests that the CPV-induced cytopathic effect was probably due to the deficiency of functional CFTR caused by CPV infection. This study uncovered the systemic changes in key cellular factors involved in CPV infection and help to understand the molecular mechanisms of the anti-cancer activity of CPV and the cytopathic effects induced by CPV infection.",2016 Jul 13,"['Zhao, Hang', 'Cheng, Yuening', 'Wang, Jianke', 'Lin, Peng', 'Yi, Li', 'Sun, Yaru', 'Ren, Jingqiang', 'Tong, Mingwei', 'Cao, Zhigang', 'Li, Jiawei', 'Deng, Jinliang', 'Cheng, Shipeng']",Sci Rep,,,True
044cd9bf656d1868e96d2213d947fff4561d0f7a,PMC,Profiling of Host Cell Response to Successive Canine Parvovirus Infection Based on Kinetic Proteomic Change Identification,http://dx.doi.org/10.1038/srep29560,PMC4942776,27406444,CC BY,"Canine parvovirus (CPV) reproduces by co-opting the resources of host cells, inevitably causing cytotoxic effects to the host cells. Feline kidney F81 cells are sensitive to CPV infection and show disparate growing statuses at different time points post-infection. This study analysed the response of F81 cells to CPV infection at successive infection time points by iTRAQ-based quantitative proteomics. Differentially expressed proteins (DEPs) during 60 h of infection and at selected time points post-infection were identified by an analysis of variance test and a two-tailed unpaired t test, respectively. DEPs with similar quantitative changes were clustered by hierarchical clustering and analysed by gene ontology enrichment, revealing that 12 h and 60 h post-infection were the optimal times to analyse the autonomous parvovirus replication and apoptosis processes, respectively. Using the Metacore(TM) database, 29 DEPs were enriched in a network involved in p53 regulation. Besides, a significantly enriched pathway suggests that the CPV-induced cytopathic effect was probably due to the deficiency of functional CFTR caused by CPV infection. This study uncovered the systemic changes in key cellular factors involved in CPV infection and help to understand the molecular mechanisms of the anti-cancer activity of CPV and the cytopathic effects induced by CPV infection.",2016 Jul 13,"['Zhao, Hang', 'Cheng, Yuening', 'Wang, Jianke', 'Lin, Peng', 'Yi, Li', 'Sun, Yaru', 'Ren, Jingqiang', 'Tong, Mingwei', 'Cao, Zhigang', 'Li, Jiawei', 'Deng, Jinliang', 'Cheng, Shipeng']",Sci Rep,,,False
a280d2019f9957487f81e4c5cf2d94a2a2f391a6,PMC,Feasibility of a randomized controlled trial to assess treatment of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Saudi Arabia: a survey of physicians,http://dx.doi.org/10.1186/s12871-016-0198-x,PMC4942900,27405596,CC BY,"BACKGROUND: The Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging respiratory pathogen with a high mortality rate and no specific treatments available to date. The purpose of this study was to determine the feasibility of conducting a randomized controlled trial (RCT) of convalescent plasma therapy for MERS-CoV-infected patients by using MERS-CoV-specific convalescent plasma obtained from previously recovered patients. METHODS: A survey was adapted from validated questionnaire originally aimed to measure network capacities and capabilities within the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC). The questionnaire was modified for this study to include 26 items that were divided into three main domains of interest: (1) the ability to care for critically ill MERS-CoV patients; (2) laboratory capacity to diagnose MERS-CoV and blood bank ability to prepare convalescent plasma; and (3), research capacity to conduct randomized controlled trials. The questionnaire was emailed to physicians. RESULTS: Of 582 physicians who were invited to the survey, 327 responded (56.2 %). The professional focus of the majority of respondents was critical care (106/249 (43 %)), pediatrics (59/249, (24 %)) or internal medicine (52/249 (21 %)) but none was blood banking. Nearly all respondents (251/263 (95 %)) reported to have access to ICU facilities within their institutions. Most respondents (219/270 (81 %)) reported that intensivists were the most physician group responsible for treatment decisions about critically ill SARI patients. While 125/165 respondents (76 %) reported that they conduct research in ICUs, and 80/161 (49.7 %) had been involved in the conduct of RCTs, including using a placebo comparison (60/161 (37 %)), only 49/226 (21 %) of respondents regularly participated in research networks. CONCLUSIONS: Our survey indicated that in the Kingdom of Saudi Arabia (KSA), ICUs are the most likely clinical locations for conducting a clinical trial of convalescent plasma therapy for MERS-CoV, and that most ICUs have experience with such research designs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12871-016-0198-x) contains supplementary material, which is available to authorized users.",2016 Jul 12,"['Arabi, Yaseen M.', 'Al-Enezi, Farhan', 'Longuere, Kajsa-Stina', 'Balkhy, Hanan H.', 'Al-Sultan, Mohamed', 'Al-Omari, Awad', 'Al-Hameed, Fahad M.', 'Carson, Gail', 'Shindo, Nahoko', 'Fowler, Robert']",BMC Anesthesiol,,,True
7636da046a6bdf1033f9078671187e65e0e231d9,PMC,Body surface infrared thermometry in patients with central venous cateter-related infections,http://dx.doi.org/10.1590/S1679-45082015AO3397,PMC4943780,26466058,CC BY,"OBJECTIVE: To evaluate if body surface temperature close to the central venous catheter insertion area is different when patients develop catheter-related bloodstream infections. METHODS: Observational cross-sectional study. Using a non-contact infrared thermometer, 3 consecutive measurements of body surface temperature were collected from 39 patients with central venous catheter on the following sites: nearby the catheter insertion area or totally implantable catheter reservoir, the equivalent contralateral region (without catheter), and forehead of the same subject. RESULTS: A total of 323 observations were collected. Respectively, both in male and female patients, disregarding the occurrence of infection, the mean temperature on the catheter area minus that on the contralateral region (mean ± standard deviation: -0.3±0.6°C versus -0.2±0.5ºC; p=0.36), and the mean temperature on the catheter area minus that on the forehead (mean ± standard deviation: -0.2±0.5°C versus -0.1±0.5ºC; p=0.3) resulted in negative values. Moreover, in infected patients, higher values were obtained on the catheter area (95%CI: 36.6-37.5ºC versus 36.3-36.5ºC; p<0.01) and by temperature subtractions: catheter area minus contralateral region (95%CI: -0.17 - +0.33ºC versus -0.33 - -0.20ºC; p=0.02) and catheter area minus forehead (95%CI: -0.02 - +0.55ºC versus -0.22 - -0.10ºC; p<0.01). CONCLUSION: Using a non-contact infrared thermometer, patients with catheter-related bloodstream infections had higher temperature values both around catheter insertion area and in the subtraction of the temperatures on the contralateral and forehead regions from those on the catheter area.",2015 Jul-Sep,"['Silvah, José Henrique', 'de Lima, Cristiane Maria Mártires', 'de Unamuno, Maria do Rosário Del Lama', 'Schetino, Marco Antônio Alves', 'Schetino, Luana Pereira Leite', 'Fassini, Priscila Giácomo', 'Brandão, Camila Fernanda Costa e Cunha Moraes', 'Basile, Anibal', 'da Cunha, Selma Freire Carvalho', 'Marchini, Julio Sergio']",Einstein (Sao Paulo),,,True
7acba31dde3af3dc1bedbde1c8167ad802fbf43e,PMC,"Productive replication of nephropathogenic infectious bronchitis virus in peripheral blood monocytic cells, a strategy for viral dissemination and kidney infection in chickens",http://dx.doi.org/10.1186/s13567-016-0354-9,PMC4944500,27412035,CC BY,"In the present study, the replication kinetics of nephropathogenic (B1648) and respiratory (Massachusetts-M41) IBV strains were compared in vitro in respiratory mucosa explants and blood monocytes (KUL01(+) cells), and in vivo in chickens to understand why some IBV strains have a kidney tropism. B1648 was replicating somewhat better than M41 in the epithelium of the respiratory mucosa explants and used more KUL01(+) cells to penetrate the deeper layers of the respiratory tract. B1648 was productively replicating in KUL01(+) monocytic cells in contrast with M41. In B1648 inoculated animals, 10(2.7–6.8) viral RNA copies/100 mg were detected in tracheal secretions at 2, 4, 6, 8, 10 and 12 days post inoculation (dpi), 10(2.4–4.5) viral RNA copies/mL in plasma at 2, 4, 6, 8, 10 and 12 dpi and 10(1.8–4.4) viral RNA copies/10(6) mononuclear cells in blood at 2, 4, 6 and 8 dpi. In M41 inoculated animals, 10(2.6–7.0) viral RNA copies/100 mg were detected in tracheal secretions at 2, 4, 6, 8 and 10 dpi, but viral RNA was not demonstrated in plasma and mononuclear cells (except in one chicken at 6 dpi). Infectious virus was detected only in plasma and mononuclear cells of the B1648 group. At euthanasia (12 dpi), viral RNA and antigen positive cells were detected in lungs, liver, spleen and kidneys of only the B1648 group and in tracheas of both the B1648 and M41 group. In conclusion, only B1648 can easily disseminate to internal organs via a cell-free and -associated viremia with KUL01(+) cells as important carrier cells.",2016 Jul 13,"['Reddy, Vishwanatha R. A. P.', 'Trus, Ivan', 'Desmarets, Lowiese M. B.', 'Li, Yewei', 'Theuns, Sebastiaan', 'Nauwynck, Hans J.']",Vet Res,,,True
88a48452ce073c9968ca2e2794fc0bccfb5dfc0f,PMC,Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding,http://dx.doi.org/10.1371/journal.pone.0159074,PMC4944999,27415624,CC BY,"Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/Mute Swan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing.",2016 Jul 14,"['Memczak, Henry', 'Lauster, Daniel', 'Kar, Parimal', 'Di Lella, Santiago', 'Volkmer, Rudolf', 'Knecht, Volker', 'Herrmann, Andreas', 'Ehrentreich-Förster, Eva', 'Bier, Frank F.', 'Stöcklein, Walter F. M.']",PLoS One,,,True
07ac15697a17a271224c7477de061f4ca6fc62aa,PMC,Topological Small-World Organization of the Fibroblastic Reticular Cell Network Determines Lymph Node Functionality,http://dx.doi.org/10.1371/journal.pbio.1002515,PMC4945005,27415420,CC BY,"Fibroblastic reticular cells (FRCs) form the cellular scaffold of lymph nodes (LNs) and establish distinct microenvironmental niches to provide key molecules that drive innate and adaptive immune responses and control immune regulatory processes. Here, we have used a graph theory-based systems biology approach to determine topological properties and robustness of the LN FRC network in mice. We found that the FRC network exhibits an imprinted small-world topology that is fully regenerated within 4 wk after complete FRC ablation. Moreover, in silico perturbation analysis and in vivo validation revealed that LNs can tolerate a loss of approximately 50% of their FRCs without substantial impairment of immune cell recruitment, intranodal T cell migration, and dendritic cell-mediated activation of antiviral CD8(+) T cells. Overall, our study reveals the high topological robustness of the FRC network and the critical role of the network integrity for the activation of adaptive immune responses.",2016 Jul 14,"['Novkovic, Mario', 'Onder, Lucas', 'Cupovic, Jovana', 'Abe, Jun', 'Bomze, David', 'Cremasco, Viviana', 'Scandella, Elke', 'Stein, Jens V.', 'Bocharov, Gennady', 'Turley, Shannon J.', 'Ludewig, Burkhard']",PLoS Biol,,,True
ac7d8fb495888876f03df56a1d3a3faa1f05e770,PMC,Inhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc,http://dx.doi.org/10.1371/journal.pntd.0004799,PMC4945073,27414047,CC BY,"Hantaviruses can cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. To enter cells, hantaviruses fuse their envelope membrane with host cell membranes. Previously, we have shown that the Gc envelope glycoprotein is the viral fusion protein sharing characteristics with class II fusion proteins. The ectodomain of class II fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. These fusion proteins can be inhibited through exogenous fusion protein fragments spanning domain III (DIII) and the stem region. Such fragments are thought to interact with the core of the fusion protein trimer during the transition from its pre-fusion to its post-fusion conformation. Based on our previous homology model structure for Gc from Andes hantavirus (ANDV), here we predicted and generated recombinant DIII and stem peptides to test whether these fragments inhibit hantavirus membrane fusion and cell entry. Recombinant ANDV DIII was soluble, presented disulfide bridges and beta-sheet secondary structure, supporting the in silico model. Using DIII and the C-terminal part of the stem region, the infection of cells by ANDV was blocked up to 60% when fusion of ANDV occurred within the endosomal route, and up to 95% when fusion occurred with the plasma membrane. Furthermore, the fragments impaired ANDV glycoprotein-mediated cell-cell fusion, and cross-inhibited the fusion mediated by the glycoproteins from Puumala virus (PUUV). The Gc fragments interfered in ANDV cell entry by preventing membrane hemifusion and pore formation, retaining Gc in a non-resistant homotrimer stage, as described for DIII and stem peptide inhibitors of class II fusion proteins. Collectively, our results demonstrate that hantavirus Gc shares not only structural, but also mechanistic similarity with class II viral fusion proteins, and will hopefully help in developing novel therapeutic strategies against hantaviruses.",2016 Jul 14,"['Barriga, Gonzalo P.', 'Villalón-Letelier, Fernando', 'Márquez, Chantal L.', 'Bignon, Eduardo A.', 'Acuña, Rodrigo', 'Ross, Breyan H.', 'Monasterio, Octavio', 'Mardones, Gonzalo A.', 'Vidal, Simon E.', 'Tischler, Nicole D.']",PLoS Negl Trop Dis,,,True
ff6ee9512267f847d91a0185e794ac98f15fe5d0,PMC,An In Vivo Selection Identifies Listeria monocytogenes Genes Required to Sense the Intracellular Environment and Activate Virulence Factor Expression,http://dx.doi.org/10.1371/journal.ppat.1005741,PMC4945081,27414028,CC BY,"Listeria monocytogenes is an environmental saprophyte and facultative intracellular bacterial pathogen with a well-defined life-cycle that involves escape from a phagosome, rapid cytosolic growth, and ActA-dependent cell-to-cell spread, all of which are dependent on the master transcriptional regulator PrfA. The environmental cues that lead to temporal and spatial control of L. monocytogenes virulence gene expression are poorly understood. In this study, we took advantage of the robust up-regulation of ActA that occurs intracellularly and expressed Cre recombinase from the actA promoter and 5’ untranslated region in a strain in which loxP sites flanked essential genes, so that activation of actA led to bacterial death. Upon screening for transposon mutants that survived intracellularly, six genes were identified as necessary for ActA expression. Strikingly, most of the genes, including gshF, spxA1, yjbH, and ohrA, are predicted to play important roles in bacterial redox regulation. The mutants identified in the genetic selection fell into three broad categories: (1) those that failed to reach the cytosolic compartment; (2) mutants that entered the cytosol, but failed to activate the master virulence regulator PrfA; and (3) mutants that entered the cytosol and activated transcription of actA, but failed to synthesize it. The identification of mutants defective in vacuolar escape suggests that up-regulation of ActA occurs in the host cytosol and not the vacuole. Moreover, these results provide evidence for two non-redundant cytosolic cues; the first results in allosteric activation of PrfA via increased glutathione levels and transcriptional activation of actA while the second results in translational activation of actA and requires yjbH. Although the precise host cues have not yet been identified, we suggest that intracellular redox stress occurs as a consequence of both host and pathogen remodeling their metabolism upon infection.",2016 Jul 14,"['Reniere, Michelle L.', 'Whiteley, Aaron T.', 'Portnoy, Daniel A.']",PLoS Pathog,,,True
8f14ee043acb5f880df53ebdd12d6edc71ddb851,PMC,Community ‐and hospital laboratory‐based surveillance for respiratory viruses,http://dx.doi.org/10.1111/irv.12387,PMC4947942,26987664,CC BY,"Traditional surveillance for respiratory viruses relies on symptom detection and laboratory detection during medically attended encounters for acute respiratory infection/influenza‐like illness (ARI/ILI). Ecological momentary reporting using text messages is a novel method for surveillance. This study compares respiratory viral activity detected through longitudinal community‐based surveillance using text message responses for sample acquisition and testing to respiratory viral activity obtained from hospital laboratory data from the same community. We demonstrate a significant correlation between community‐ and hospital laboratory‐based surveillance for most respiratory viruses, although the relative proportions of viruses detected in the community and hospital differed significantly.",2016 Sep 27,"['Zachariah, Philip', 'Whittier, Susan', 'Reed, Carrie', 'LaRussa, Philip', 'Larson, Elaine L.', 'Vargas, Celibell Y.', 'Saiman, Lisa', 'Stockwell, Melissa S.']",Influenza Other Respir Viruses,,,True
a3ff62cdc7cd33bb6618950b28fe649bf95ef6de,PMC,"Type‐specific clinical characteristics of adenovirus‐associated influenza‐like illness at five US military medical centers, 2009–2014",http://dx.doi.org/10.1111/irv.12392,PMC4947946,27062998,CC BY,"BACKGROUND: Adenovirus is a recognized cause of influenza‐like illness (ILI). The proportion of ILI attributable to adenovirus is not known. Moreover, knowledge gaps remain with respect to the epidemiologic, virologic, and clinical characteristics of adenovirus‐associated ILI among otherwise healthy individuals. METHODS: An observational, longitudinal study of <65‐year‐old patients with febrile ILI at five medical centers was conducted from 2009 to 2014. Nasopharyngeal specimens obtained at enrollment were first tested by single‐reaction PCR for adenovirus, then further evaluated by a multiplex PCR assay for other respiratory viral pathogens. Symptoms over a 28‐day period were collected. RESULTS: We enrolled 1536 individuals, among whom 43 (2·8%) were positive for adenovirus. The median age of cases was 3·4 years (range: 4 months to 41 years). Three were hospitalized. Species and serotype information was available for 33 (76·7%) cases. Species C (n = 21) was the most common, followed by B3 (n = 9) and one each of E4a, D46, and A. Species C infections were more frequent in children (P < 0·01). Half of the cases were positive for at least one other respiratory viral pathogen. Symptoms were generally mild and most commonly included cough (90%), fatigue (79%), rhinorrhea (74%), loss of appetite (71%), and sore throat (64%). Children with non‐C adenovirus infection were more likely to report sore throat (P = 0·05) and hoarseness (P = 0·06) than those with species C infection. CONCLUSIONS: Adenovirus is frequently detected with other respiratory viruses. Persons with non‐C adenovirus infections reported more severe symptoms, suggesting there may be species‐specific differences in virulence and/or host response to infection.",2016 Sep 13,"['Koren, Michael A.', 'Arnold, John C.', 'Fairchok, Mary P.', 'Lalani, Tahaniyat', 'Danaher, Patrick J.', 'Schofield, Christina M.', 'Rajnik, Michael', 'Hansen, Erin A.', 'Mor, Deepika', 'Chen, Wei‐Ju', 'Ridoré, Michelande', 'Burgess, Timothy H.', 'Millar, Eugene V.']",Influenza Other Respir Viruses,,,True
3a8c6a1683a063b6fc3c1bd689ff9c1b83723b4e,PMC,"Viral etiology of severe acute respiratory infections in hospitalized children in Cameroon, 2011–2013",http://dx.doi.org/10.1111/irv.12391,PMC4947949,27012372,CC BY,"BACKGROUND: Severe acute respiratory illness (SARI) is recognized as an important cause of morbidity, mortality, and hospitalization among children in developing countries. Little is known, however, in tropical countries like Cameroon about the cause and seasonality of respiratory infections, especially in hospitalized settings. Objectives: Our study investigates the viral etiology and seasonality of SARI in hospitalized children in Yaounde, Cameroon. METHODS: Prospective clinic surveillance was conducted to identify hospitalized children aged ≤15 years presenting with respiratory symptoms ≤5‐day duration. Demographic and clinical data, and respiratory specimens were collected. Nasopharyngeal samples were tested for 17 respiratory viruses using a multiplex polymerase chain reaction. The viral distribution and demographic data were statistically analyzed. RESULTS: From September 2011 through September 2013, 347 children aged ≤15 years were enrolled. At least one virus was identified in each of 65·4% children, of which 29·5% were coinfections; 27·3% were positive for human adenovirus (hAdV), 13·2% for human respiratory syncytial virus (hRSV), 11·5% for rhinovirus/enterovirus (RV/EV), 10·6% for human bocavirus (hBoV), 9·8% for influenza virus (Inf), 6·6% for human parainfluenza virus (hPIV), 5·7% for human coronavirus (hCoV), and 2·3% for human metapneumovirus (hMPV). While hRSV showed seasonal patterns, hAdV and RV/EV were detected throughout the year and no evident temporal patterns were observed for the remaining viruses. CONCLUSION: Respiratory viruses were associated with a high burden of hospitalizations among children in Cameroon. Nevertheless, additional studies evaluating asymptomatic Cameroonian children will be important in understanding the relationship between viral carriage and disease.",2016 Sep 9,"['Kenmoe, Sebastien', 'Tchendjou, Patrice', 'Vernet, Marie‐Astrid', 'Moyo‐Tetang, Suzie', 'Mossus, Tatiana', 'Njankouo‐Ripa, Mohamadou', 'Kenne, Angeladine', 'Penlap Beng, Véronique', 'Vabret, Astrid', 'Njouom, Richard']",Influenza Other Respir Viruses,,,True
96cd80ad6f658fdc8b0d5e8ce4e1eb1f1daa87f5,PMC,The effect of herd formation among healthcare investors on health sector growth in China,http://dx.doi.org/10.1186/s12939-016-0393-x,PMC4950590,27436298,CC BY,"BACKGROUND: China has become the world‘s second largest healthcare market based on a recent report by the World Health Organization. Eventhough China achieved universal health insurance coverage in 2011, representing the largest expansion of insurance coverage in human history achieved; health inequality remains endemic in China. Lessons from the effect of market crisis on health equity in Europe and other places has reignited interest in exploring the potential healthcare market aberrations that can trigger distributive injustice in healthcare resource allocation among China’s provinces. Recently, many healthcare investors in China have become more concerned about capital preservation, and are responding by abandoning long term investments strategies in healthcare. This investment withdrawal en mass is perceived to be influenced by herding tendencies and can trigger or consolidate endemic health inequality. METHODS: Our study simultaneously employs four testing models (two state spaced models and two return dispersion models) to establish the existence of procyclical (herding) behavior among the stocks and its health equity implications. These are applied to a large set of data to compare and contrast results of herd formation among investors in fourteen healthcare sectors in China. RESULTS: The study reveals that apart from the cross sectional standard deviation (CSSD) model, the remaining two models and our augmented state space model yields significant evidence of herding in all subsectors of the healthcare market. We also find that the herding effect is more prominent during down movements of the market. CONCLUSION: Herding behavior may lead to contemporaneous loss of investor confidence and capital withdrawal and thereby deprive the healthcare sector of the much needed capital for expansion. Thus there may be obvious delay in efforts to bridge the gap in access to healthcare facilities, medical support services, medical supplies, pharmaceuticals, biotechnology, diagnostic substances, medical laboratory and advanced medical equipment across China. Moreover, a potential crash in the healthcare market is possible in the healthcare sector as a result of persistent herding tendencies among investors and that may have more damaging consequences for health inequality in China.",2016 Jul 19,"['Lulin, Zhou', 'Antwi, Henry Asante', 'Wang, Wenxin', 'Yiranbon, Ethel', 'Marfo, Emmanuel Opoku', 'Acheampong, Patrick']",Int J Equity Health,,,True
1b050ba5ac020c50042f89a5f4936404ab2f507f,PMC,Heterogeneity in District-Level Transmission of Ebola Virus Disease during the 2013-2015 Epidemic in West Africa,http://dx.doi.org/10.1371/journal.pntd.0004867,PMC4951043,27434164,CC BY,"The Ebola virus disease (EVD) epidemic in West Africa in 2013–2015 spread heterogeneously across the three hardest-hit countries Guinea, Liberia and Sierra Leone and the estimation of national transmission of EVD provides little information about local dynamics. To investigate district-level transmissibility of EVD, we applied a statistical modelling approach to estimate the basic reproduction number (R(0)) for each affected district and each country using weekly incident case numbers. We estimated growth rates during the early exponential phase of the outbreak using exponential regression of the case counts on the first eight weeks since onset. To take into account the heterogeneity between and within countries, we fitted a mixed effects model and calculated R(0) based on the predicted individual growth rates and the reported serial interval distribution. At district level, R(0) ranged from 0.36 (Dubréka) to 1.72 (Beyla) in Guinea, from 0.53 (Maryland) to 3.37 (Margibi) in Liberia and from 1.14 (Koinadugu) to 2.73 (Western Rural) in Sierra Leone. At national level, we estimated an R(0) of 0.97 (95% CI 0.77–1.18) for Guinea, 1.26 (95% CI 0.98–1.55) for Liberia and 1.66 (95% CI 1.32–2.00) for Sierra Leone. Socio-demographic variables related to urbanisation such as high population density and high wealth index were found positively associated with R(0) suggesting that the consequences of fast urban growth in West Africa may have contributed to the increased spread of EVD.",2016 Jul 19,"['Krauer, Fabienne', 'Gsteiger, Sandro', 'Low, Nicola', 'Hansen, Christian H.', 'Althaus, Christian L.']",PLoS Negl Trop Dis,,,True
6e2133224869e531889ce6d7c7cb0729e4f2c2c6,PMC,Heterogeneity in District-Level Transmission of Ebola Virus Disease during the 2013-2015 Epidemic in West Africa,http://dx.doi.org/10.1371/journal.pntd.0004867,PMC4951043,27434164,CC BY,"The Ebola virus disease (EVD) epidemic in West Africa in 2013–2015 spread heterogeneously across the three hardest-hit countries Guinea, Liberia and Sierra Leone and the estimation of national transmission of EVD provides little information about local dynamics. To investigate district-level transmissibility of EVD, we applied a statistical modelling approach to estimate the basic reproduction number (R(0)) for each affected district and each country using weekly incident case numbers. We estimated growth rates during the early exponential phase of the outbreak using exponential regression of the case counts on the first eight weeks since onset. To take into account the heterogeneity between and within countries, we fitted a mixed effects model and calculated R(0) based on the predicted individual growth rates and the reported serial interval distribution. At district level, R(0) ranged from 0.36 (Dubréka) to 1.72 (Beyla) in Guinea, from 0.53 (Maryland) to 3.37 (Margibi) in Liberia and from 1.14 (Koinadugu) to 2.73 (Western Rural) in Sierra Leone. At national level, we estimated an R(0) of 0.97 (95% CI 0.77–1.18) for Guinea, 1.26 (95% CI 0.98–1.55) for Liberia and 1.66 (95% CI 1.32–2.00) for Sierra Leone. Socio-demographic variables related to urbanisation such as high population density and high wealth index were found positively associated with R(0) suggesting that the consequences of fast urban growth in West Africa may have contributed to the increased spread of EVD.",2016 Jul 19,"['Krauer, Fabienne', 'Gsteiger, Sandro', 'Low, Nicola', 'Hansen, Christian H.', 'Althaus, Christian L.']",PLoS Negl Trop Dis,,,False
e6b79340345095e1d161ff41e5258d1c1d1009e0,PMC,Heterogeneity in District-Level Transmission of Ebola Virus Disease during the 2013-2015 Epidemic in West Africa,http://dx.doi.org/10.1371/journal.pntd.0004867,PMC4951043,27434164,CC BY,"The Ebola virus disease (EVD) epidemic in West Africa in 2013–2015 spread heterogeneously across the three hardest-hit countries Guinea, Liberia and Sierra Leone and the estimation of national transmission of EVD provides little information about local dynamics. To investigate district-level transmissibility of EVD, we applied a statistical modelling approach to estimate the basic reproduction number (R(0)) for each affected district and each country using weekly incident case numbers. We estimated growth rates during the early exponential phase of the outbreak using exponential regression of the case counts on the first eight weeks since onset. To take into account the heterogeneity between and within countries, we fitted a mixed effects model and calculated R(0) based on the predicted individual growth rates and the reported serial interval distribution. At district level, R(0) ranged from 0.36 (Dubréka) to 1.72 (Beyla) in Guinea, from 0.53 (Maryland) to 3.37 (Margibi) in Liberia and from 1.14 (Koinadugu) to 2.73 (Western Rural) in Sierra Leone. At national level, we estimated an R(0) of 0.97 (95% CI 0.77–1.18) for Guinea, 1.26 (95% CI 0.98–1.55) for Liberia and 1.66 (95% CI 1.32–2.00) for Sierra Leone. Socio-demographic variables related to urbanisation such as high population density and high wealth index were found positively associated with R(0) suggesting that the consequences of fast urban growth in West Africa may have contributed to the increased spread of EVD.",2016 Jul 19,"['Krauer, Fabienne', 'Gsteiger, Sandro', 'Low, Nicola', 'Hansen, Christian H.', 'Althaus, Christian L.']",PLoS Negl Trop Dis,,,False
58383a13c8f80823bd6cf3516faf38c1687994a7,PMC,Heterogeneity in District-Level Transmission of Ebola Virus Disease during the 2013-2015 Epidemic in West Africa,http://dx.doi.org/10.1371/journal.pntd.0004867,PMC4951043,27434164,CC BY,"The Ebola virus disease (EVD) epidemic in West Africa in 2013–2015 spread heterogeneously across the three hardest-hit countries Guinea, Liberia and Sierra Leone and the estimation of national transmission of EVD provides little information about local dynamics. To investigate district-level transmissibility of EVD, we applied a statistical modelling approach to estimate the basic reproduction number (R(0)) for each affected district and each country using weekly incident case numbers. We estimated growth rates during the early exponential phase of the outbreak using exponential regression of the case counts on the first eight weeks since onset. To take into account the heterogeneity between and within countries, we fitted a mixed effects model and calculated R(0) based on the predicted individual growth rates and the reported serial interval distribution. At district level, R(0) ranged from 0.36 (Dubréka) to 1.72 (Beyla) in Guinea, from 0.53 (Maryland) to 3.37 (Margibi) in Liberia and from 1.14 (Koinadugu) to 2.73 (Western Rural) in Sierra Leone. At national level, we estimated an R(0) of 0.97 (95% CI 0.77–1.18) for Guinea, 1.26 (95% CI 0.98–1.55) for Liberia and 1.66 (95% CI 1.32–2.00) for Sierra Leone. Socio-demographic variables related to urbanisation such as high population density and high wealth index were found positively associated with R(0) suggesting that the consequences of fast urban growth in West Africa may have contributed to the increased spread of EVD.",2016 Jul 19,"['Krauer, Fabienne', 'Gsteiger, Sandro', 'Low, Nicola', 'Hansen, Christian H.', 'Althaus, Christian L.']",PLoS Negl Trop Dis,,,True
e0f39f2d61d66f276287f181454ae85cdafb7ffa,PMC,Respiratory Virus Detection and Clinical Diagnosis in Children Attending Day Care,http://dx.doi.org/10.1371/journal.pone.0159196,PMC4951077,27433803,CC BY,"BACKGROUND: Respiratory viruses often have been studied in children with respiratory tract infection (RTI), but less knowledge exists about viruses in asymptomatic children. We have studied the occurrence of a broad panel of respiratory viruses in apparently healthy children attending day care, taking into account the influence of possible confounding factors, such as age, clinical signs of respiratory tract infection (RTI), location (day-care section) and season. METHODS: We have studied 161 children in two day-care centers, each with separate sections for younger and older children, during four autumn and winter visits over a two-year period. A total of 355 clinical examinations were performed, and 343 nasopharyngeal samples (NPS) were analyzed by semi-quantitative, real-time, polymerase chain reaction (PCR) tests for 19 respiratory pathogens. RESULT: Forty-three percent of all NPS were PCR-positive for ≥ 1 of 13 virus species, with high species variation during visits. Rhinovirus 26% (88/343 NPS), enterovirus 12% (40/343) and parechovirus 9% (30/343) were detected in every visit, and the rates varied in relation to age, day-care section and season. Ten other viruses were detected in ≤ 3% of the NPS. Generally, viruses occurred together in the NPS. In 24% (79/331) of the clinical examinations with available NPS, the children had clear signs of RTI, while in 41% (135/331) they had mild signs, and in 35% (117/331) the children had no signs of RTI. Moreover, viruses were found in 70% (55/79) of children with clear signs of RTI, in 41% (55/135) with mild signs and in 30% (35/117) without any signs of RTI (p < 0.001). CONCLUSIONS: Positive PCR tests for respiratory viruses, particularly picornaviruses, were frequently detected in apparently healthy children attending day care. Virus detection rates were related to age, presence of clinical signs of RTI, location in day care and season.",2016 Jul 19,"['Moe, Nina', 'Pedersen, Bård', 'Nordbø, Svein Arne', 'Skanke, Lars Høsøien', 'Krokstad, Sidsel', 'Smyrnaios, Anastasios', 'Døllner, Henrik']",PLoS One,,,True
04299cd1ecb45c984de64da12daf3ccc1fe2abe2,PMC,Intestinal microbiota and chronic constipation,http://dx.doi.org/10.1186/s40064-016-2821-1,PMC4951383,27478747,CC BY,"Chronic constipation is a prevalent, burdensome gastrointestinal disorder whose aetiology and pathophysiology remains poorly understood and is most likely multifactorial. Differences in the composition of the intestinal microbiota have been demonstrated when constipated patients and healthy controls have been compared. Growing evidence indicates that alterations of intestinal microbiota may contribute to constipation and constipation-related symptoms. The intestinal microbiota is a collection of microorganisms that live within the gastrointestinal tract, and perform many important health-promoting functions. The intestinal microbiota aids in the breakdown of food products into absorbable nutrients, stimulates the host immune system, prevents growth of pathogenic bacteria and produces a great variety of biologically important compounds. In this review, we will summarize the current evidence supporting roles of the intestinal microbiota in the pathogenesis and management of chronic constipation. The discussion will shed light on the novel mechanisms of intestinal microbiota and gut function interactions, which is invaluable in ultimately developing new therapeutic tools for the treatment of chronic constipation.",2016 Jul 19,"['Zhao, Ying', 'Yu, Yan-Bo']",Springerplus,,,True
a21bd16035d028aae34bab89c3be720ffec176a1,PMC,"Can free open access resources strengthen knowledge-based emerging public health priorities, policies and programs in Africa?",http://dx.doi.org/10.12688/f1000research.8662.1,PMC4955019,27508058,CC BY,"Tackling emerging epidemics and infectious diseases burden in Africa requires increasing unrestricted open access and free use or reuse of regional and global policies reforms as well as timely communication capabilities and strategies. Promoting, scaling up data and information sharing between African researchers and international partners are of vital importance in accelerating open access at no cost. Free Open Access (FOA) health data and information acceptability, uptake tactics and sustainable mechanisms are urgently needed. These are critical in establishing real time and effective knowledge or evidence-based translation, proven and validated approaches, strategies and tools to strengthen and revamp health systems. As such, early and timely access to needed emerging public health information is meant to be instrumental and valuable for policy-makers, implementers, care providers, researchers, health-related institutions and stakeholders including populations when guiding health financing, and planning contextual programs.",2016 May 9,"['Tambo, Ernest', 'Madjou, Ghislaine', 'Khayeka-Wandabwa, Christopher', 'Tekwu, Emmanuel N.', 'Olalubi, Oluwasogo A.', 'Midzi, Nicolas', 'Bengyella, Louis', 'Adedeji, Ahmed A.', 'Ngogang, Jeanne Y.']",F1000Res,,,True
9dc7d12caa315d1608b7e1310aa4ba033d50d8e0,PMC,Airborne biological hazards and urban transport infrastructure: current challenges and future directions,http://dx.doi.org/10.1007/s11356-016-7064-8,PMC4956722,27318484,CC BY,"Exposure to airborne biological hazards in an ever expanding urban transport infrastructure and highly diverse mobile population is of growing concern, in terms of both public health and biosecurity. The existing policies and practices on design, construction and operation of these infrastructures may have severe implications for airborne disease transmission, particularly, in the event of a pandemic or intentional release of biological of agents. This paper reviews existing knowledge on airborne disease transmission in different modes of transport, highlights the factors enhancing the vulnerability of transport infrastructures to airborne disease transmission, discusses the potential protection measures and identifies the research gaps in order to build a bioresilient transport infrastructure. The unification of security and public health research, inclusion of public health security concepts at the design and planning phase, and a holistic system approach involving all the stakeholders over the life cycle of transport infrastructure hold the key to mitigate the challenges posed by biological hazards in the twenty-first century transport infrastructure.",2016 Jun 18,"['Nasir, Zaheer Ahmad', 'Campos, Luiza Cintra', 'Christie, Nicola', 'Colbeck, Ian']",Environ Sci Pollut Res Int,,,True
6a5ec0f5b18ea19bc152ad79a1b72043385a8f3f,PMC,Predicting the international spread of Middle East respiratory syndrome (MERS),http://dx.doi.org/10.1186/s12879-016-1675-z,PMC4957429,27449387,CC BY,"BACKGROUND: The Middle East respiratory syndrome (MERS) associated coronavirus has been imported via travelers into multiple countries around the world. In order to support risk assessment practice, the present study aimed to devise a novel statistical model to quantify the country-level risk of experiencing an importation of MERS case. METHODS: We analyzed the arrival time of each reported MERS importation around the world, i.e., the date on which imported cases entered a specific country, which was modeled as a dependent variable in our analysis. We also used openly accessible data including the airline transportation network to parameterize a hazard-based risk prediction model. The hazard was assumed to follow an inverse function of the effective distance (i.e., the minimum effective length of a path from origin to destination), which was calculated from the airline transportation data, from Saudi Arabia to each country. Both country-specific religion and the incidence data of MERS in Saudi Arabia were used to improve our model prediction. RESULTS: Our estimates of the risk of MERS importation appeared to be right skewed, which facilitated the visual identification of countries at highest risk of MERS importations in the right tail of the distribution. The simplest model that relied solely on the effective distance yielded the best predictive performance (Area under the curve (AUC) = 0.943) with 100 % sensitivity and 79.6 % specificity. Out of the 30 countries estimated to be at highest risk of MERS case importation, 17 countries (56.7 %) have already reported at least one importation of MERS. Although model fit measured by Akaike Information Criterion (AIC) was improved by including country-specific religion (i.e. Muslim majority country), the predictive performance as measured by AUC was not improved after accounting for this covariate. CONCLUSIONS: Our relatively simple statistical model based on the effective distance derived from the airline transportation network data was found to help predicting the risk of importing MERS at the country level. The successful application of the effective distance model to predict MERS importations, particularly when computationally intensive large-scale transmission models may not be immediately applicable could have been benefited from the particularly low transmissibility of the MERS coronavirus.",2016 Jul 22,"['Nah, Kyeongah', 'Otsuki, Shiori', 'Chowell, Gerardo', 'Nishiura, Hiroshi']",BMC Infect Dis,,,True
4a4829a678305f54711666d194597971627c7b48,PMC,Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets,http://dx.doi.org/10.1371/journal.pone.0159625,PMC4957826,27448168,CC BY,"Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina). This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health. To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described. The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells. Virus infection was restricted to the respiratory tract. The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections. To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation. These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium. Virus was isolated only from the respiratory tract. In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication. Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics. Productive infection of ferrets indicates that seal/H10N7 may possess a zoonotic potential. This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals and thus humans.",2016 Jul 22,"['van den Brand, Judith M. A.', 'Wohlsein, Peter', 'Herfst, Sander', 'Bodewes, Rogier', 'Pfankuche, Vanessa M.', 'van de Bildt, Marco W. G.', 'Seehusen, Frauke', 'Puff, Christina', 'Richard, Mathilde', 'Siebert, Ursula', 'Lehnert, Kristina', 'Bestebroer, Theo', 'Lexmond, Pascal', 'Fouchier, Ron A. M.', 'Prenger-Berninghoff, Ellen', 'Herbst, Werner', 'Koopmans, Marion', 'Osterhaus, Albert D. M. E.', 'Kuiken, Thijs', 'Baumgärtner, Wolfgang']",PLoS One,,,True
f17288f985aa9c44a23132028973162a800726f4,PMC,Lectin-Glycan Interaction Network-Based Identification of Host Receptors of Microbial Pathogenic Adhesins,http://dx.doi.org/10.1128/mBio.00584-16,PMC4958244,27406561,CC BY,"The first step in the infection of humans by microbial pathogens is their adherence to host tissue cells, which is frequently based on the binding of carbohydrate-binding proteins (lectin-like adhesins) to human cell receptors that expose glycans. In only a few cases have the human receptors of pathogenic adhesins been described. A novel strategy—based on the construction of a lectin-glycan interaction (LGI) network—to identify the potential human binding receptors for pathogenic adhesins with lectin activity was developed. The new approach is based on linking glycan array screening results of these adhesins to a human glycoprotein database via the construction of an LGI network. This strategy was used to detect human receptors for virulent Escherichia coli (FimH adhesin), and the fungal pathogens Candida albicans (Als1p and Als3p adhesins) and C. glabrata (Epa1, Epa6, and Epa7 adhesins), which cause candidiasis. This LGI network strategy allows the profiling of potential adhesin binding receptors in the host with prioritization, based on experimental binding data, of the most relevant interactions. New potential targets for the selected adhesins were predicted and experimentally confirmed. This methodology was also used to predict lectin interactions with envelope glycoproteins of human-pathogenic viruses. It was shown that this strategy was successful in revealing that the FimH adhesin has anti-HIV activity.",2016 Jul 12,"['Ielasi, Francesco S.', 'Alioscha-Perez, Mitchel', 'Donohue, Dagmara', 'Claes, Sandra', 'Sahli, Hichem', 'Schols, Dominique', 'Willaert, Ronnie G.']",mBio,,,True
d24a70c5203617db24e9777727d824bcad5597c7,PMC,Identification and characterization of the role of c-terminal Src kinase in dengue virus replication,http://dx.doi.org/10.1038/srep30490,PMC4960526,27457684,CC BY,"We screened a siRNA library targeting human tyrosine kinases in Huh-7 cells and identified c-terminal Src kinase (Csk) as one of the kinases involved in dengue virus replication. Knock-down of Csk expression by siRNAs or inhibition of Csk by an inhibitor reduced dengue virus RNA levels but did not affect viral entry. Csk partially colocalized with viral replication compartments. Dengue infection was drastically reduced in cells lacking the three ubiquitous src family kinases, Src, Fyn and Yes. Csk knock-down in these cells failed to block dengue virus replication suggesting that the effect of Csk is via regulation of Src family kinases. Csk was found to be hyper-phosphorylated during dengue infection and inhibition of protein kinase A led to a block in Csk phosphorylation and dengue virus replication. Overexpression studies suggest an important role for the kinase and SH3 domains in this process. Our results identified a novel role for Csk as a host tyrosine kinase involved in dengue virus replication and provide further insights into the role of host factors in dengue replication.",2016 Jul 26,"['Kumar, Rinki', 'Agrawal, Tanvi', 'Khan, Naseem Ahmed', 'Nakayama, Yuji', 'Medigeshi, Guruprasad R.']",Sci Rep,,,True
013efebeacfb3148ec21bb8d83b040dd0437ea3a,PMC,Identification and characterization of the role of c-terminal Src kinase in dengue virus replication,http://dx.doi.org/10.1038/srep30490,PMC4960526,27457684,CC BY,"We screened a siRNA library targeting human tyrosine kinases in Huh-7 cells and identified c-terminal Src kinase (Csk) as one of the kinases involved in dengue virus replication. Knock-down of Csk expression by siRNAs or inhibition of Csk by an inhibitor reduced dengue virus RNA levels but did not affect viral entry. Csk partially colocalized with viral replication compartments. Dengue infection was drastically reduced in cells lacking the three ubiquitous src family kinases, Src, Fyn and Yes. Csk knock-down in these cells failed to block dengue virus replication suggesting that the effect of Csk is via regulation of Src family kinases. Csk was found to be hyper-phosphorylated during dengue infection and inhibition of protein kinase A led to a block in Csk phosphorylation and dengue virus replication. Overexpression studies suggest an important role for the kinase and SH3 domains in this process. Our results identified a novel role for Csk as a host tyrosine kinase involved in dengue virus replication and provide further insights into the role of host factors in dengue replication.",2016 Jul 26,"['Kumar, Rinki', 'Agrawal, Tanvi', 'Khan, Naseem Ahmed', 'Nakayama, Yuji', 'Medigeshi, Guruprasad R.']",Sci Rep,,,False
50aa5eba3f398675c8f3c53a819aca7fb8b4af33,PMC,Assessing worldwide research activity on probiotics in pediatrics using Scopus database: 1994–2014,http://dx.doi.org/10.1186/s40413-016-0116-1,PMC4960683,27504147,CC BY,"BACKGROUND: A wide variety of probiotic products has been introduced into the market in the past decade. Research trends and activity on probiotics help understand how these products were evolved and their potential future role in medicine. The objective of this study was to assess the research activity on probiotics in pediatrics using bibliometric indicators and network visualization. METHODS: Original and review articles on probiotics in pediatrics published worldwide were retrieved from SciVerse, Scopus (1994–2014) and analyzed. VOSviewer was used for network visualization. RESULTS: The total number of documents published on probiotics in pediatrics was 2817. Research activity on probiotics in pediatrics showed approximately 90- fold increase during the study period. Approximately 22 % of published articles originated from USA and has the greatest share, however, Finland ranked first when data were stratified by population or income. The most productive institution in this field was Turku University in Finland with 82 (2.91 %) articles. Half of the prolific authors were also from Finland. Most of the published research activity appeared in Journal of Pediatric Gastroenterology and Nutrition. Most frequently encountered title terms include nutrition, infant formula, necrotizing enetrocolitis, allergy, and diarrhea. The total number of citations for the retreived documents documents was 70991, and the average citation per article was 25.20. CONCLUSIONS: Interest in probiotic research and its potential benefits in pediatric ailments is relatively recent but significantly increasing. Bibliometric analysis can be used as an indicator of the importance and growth of probiotic use in pediatrics.",2016 Jul 25,"['Sweileh, Waleed M.', 'Shraim, Naser Y.', 'Al-Jabi, Samah W.', 'Sawalha, Ansam F.', 'Rahhal, Belal', 'Khayyat, Rasha A.', 'Zyoud, Sa’ed H.']",World Allergy Organ J,,,True
5b15c62ee761d6eefeb7d2ef023f804bfdc41edc,PMC,Optimal Decision Model for Sustainable Hospital Building Renovation—A Case Study of a Vacant School Building Converting into a Community Public Hospital,http://dx.doi.org/10.3390/ijerph13070630,PMC4962171,27347986,CC BY,"Much attention has been paid to hospitals environments since modern pandemics have emerged. The building sector is considered to be the largest world energy consumer, so many global organizations are attempting to create a sustainable environment in building construction by reducing energy consumption. Therefore, maintaining high standards of hygiene while reducing energy consumption has become a major task for hospitals. This study develops a decision model based on genetic algorithms and A* graph search algorithms to evaluate existing hospital environmental conditions and to recommend an optimal scheme of sustainable renovation strategies, considering trade-offs among minimal renovation cost, maximum quality improvement, and low environmental impact. Reusing vacant buildings is a global and sustainable trend. In Taiwan, for example, more and more school space will be unoccupied due to a rapidly declining birth rate. Integrating medical care with local community elder-care efforts becomes important because of the aging population. This research introduces a model that converts a simulated vacant school building into a community public hospital renovation project in order to validate the solutions made by hospital managers and suggested by the system. The result reveals that the system performs well and its solutions are more successful than the actions undertaken by decision-makers. This system can improve traditional hospital building condition assessment while making it more effective and efficient.",2016 Jul 24,"['Juan, Yi-Kai', 'Cheng, Yu-Ching', 'Perng, Yeng-Horng', 'Castro-Lacouture, Daniel']",Int J Environ Res Public Health,,,True
c6e40c6e9f16528e3a7495481311cff9a886d86e,PMC,Sounding the Alarm: Health in the Anthropocene,http://dx.doi.org/10.3390/ijerph13070665,PMC4962206,27376314,CC BY,"There is growing scientific and public recognition that human actions, directly and indirectly, have profoundly changed the Earth system, in a still accelerating process, increasingly called the “Anthropocene”. Planetary transformation, including of the atmosphere, climate, ecosystems and biodiversity, has enormous implications for human health, many of which are deeply disturbing, especially in low-income settings. A few health consequences of the Anthropocene have been partially recognized, including within environmental epidemiology, but their long-term consequences remain poorly understood and greatly under-rated. For example Syria could be a “sentinel” population, giving a glimpse to a much wider dystopian future. Health-Earth is a research network, co-founded in 2014, which seeks, with other groups, to catalyse a powerful curative response by the wider health community. This paper builds on a symposium presented by Health-Earth members at the 2015 conference of the International Society for Environmental Epidemiology. It reviews and synthesizes parts of the large literature relevant to the interaction between the changing Earth system and human health. It concludes that this topic should be prominent within future environmental epidemiology and public health. Created by our species, these challenges may be soluble, but solutions require far more understanding and resources than are currently being made available.",2016 Jul 30,"Butler, Colin D.",Int J Environ Res Public Health,,,True
bf0bd7e3007cf87a4907ecf1bbf819d28e5c3c63,PMC,Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus,http://dx.doi.org/10.1371/journal.pone.0159709,PMC4963090,27463224,CC0,"Respiratory syncytial virus (RSV) is a significant cause of severe respiratory illness worldwide, particularly in infants, young children, and the elderly. Although no licensed vaccine is currently available, an engineered version of the metastable RSV fusion (F) surface glycoprotein—stabilized in the pre-fusion (pre-F) conformation by “DS-Cav1” mutations—elicits high titer RSV-neutralizing responses. Moreover, pre-F-specific antibodies, often against the neutralization-sensitive antigenic site Ø in the membrane-distal head region of trimeric F glycoprotein, comprise a substantial portion of the human response to natural RSV infection. To focus the vaccine-elicited response to antigenic site Ø, we designed a series of RSV F immunogens that comprised the membrane-distal head of the F glycoprotein in its pre-F conformation. These “head-only” immunogens formed monomers, dimers, and trimers. Antigenic analysis revealed that a majority of the 70 engineered head-only immunogens displayed reactivity to site Ø-targeting antibodies, which was similar to that of the parent RSV F DS-Cav1 trimers, often with increased thermostability. We evaluated four of these head-only immunogens in detail, probing their recognition by antibodies, their physical stability, structure, and immunogenicity. When tested in naïve mice, a head-only trimer, half the size of the parent RSV F trimer, induced RSV titers, which were statistically comparable to those induced by DS-Cav1. When used to boost DS-Cav1-primed mice, two head-only RSV F immunogens, a dimer and a trimer, boosted RSV-neutralizing titers to levels that were comparable to those boosted by DS-Cav1, although with higher site Ø-directed responses. Our results provide proof-of-concept for the ability of the smaller head-only RSV F immunogens to focus the vaccine-elicited response to antigenic site Ø. Decent primary immunogenicity, enhanced physical stability, potential ease of manufacture, and potent immunogenicity upon boosting suggest these head-only RSV F immunogens, engineered to retain the pre-fusion conformation, may have advantages as candidate RSV vaccines.",2016 Jul 27,"['Boyington, Jeffrey C.', 'Joyce, M. Gordon', 'Sastry, Mallika', 'Stewart-Jones, Guillaume B. E.', 'Chen, Man', 'Kong, Wing-Pui', 'Ngwuta, Joan O.', 'Thomas, Paul V.', 'Tsybovsky, Yaroslav', 'Yang, Yongping', 'Zhang, Baoshan', 'Chen, Lei', 'Druz, Aliaksandr', 'Georgiev, Ivelin S.', 'Ko, Kiyoon', 'Zhou, Tongqing', 'Mascola, John R.', 'Graham, Barney S.', 'Kwong, Peter D.']",PLoS One,,,True
f8a4ffd24e2b938c844b4affc6d03ffe51f0ff16,PMC,Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus,http://dx.doi.org/10.1371/journal.pone.0159709,PMC4963090,27463224,CC0,"Respiratory syncytial virus (RSV) is a significant cause of severe respiratory illness worldwide, particularly in infants, young children, and the elderly. Although no licensed vaccine is currently available, an engineered version of the metastable RSV fusion (F) surface glycoprotein—stabilized in the pre-fusion (pre-F) conformation by “DS-Cav1” mutations—elicits high titer RSV-neutralizing responses. Moreover, pre-F-specific antibodies, often against the neutralization-sensitive antigenic site Ø in the membrane-distal head region of trimeric F glycoprotein, comprise a substantial portion of the human response to natural RSV infection. To focus the vaccine-elicited response to antigenic site Ø, we designed a series of RSV F immunogens that comprised the membrane-distal head of the F glycoprotein in its pre-F conformation. These “head-only” immunogens formed monomers, dimers, and trimers. Antigenic analysis revealed that a majority of the 70 engineered head-only immunogens displayed reactivity to site Ø-targeting antibodies, which was similar to that of the parent RSV F DS-Cav1 trimers, often with increased thermostability. We evaluated four of these head-only immunogens in detail, probing their recognition by antibodies, their physical stability, structure, and immunogenicity. When tested in naïve mice, a head-only trimer, half the size of the parent RSV F trimer, induced RSV titers, which were statistically comparable to those induced by DS-Cav1. When used to boost DS-Cav1-primed mice, two head-only RSV F immunogens, a dimer and a trimer, boosted RSV-neutralizing titers to levels that were comparable to those boosted by DS-Cav1, although with higher site Ø-directed responses. Our results provide proof-of-concept for the ability of the smaller head-only RSV F immunogens to focus the vaccine-elicited response to antigenic site Ø. Decent primary immunogenicity, enhanced physical stability, potential ease of manufacture, and potent immunogenicity upon boosting suggest these head-only RSV F immunogens, engineered to retain the pre-fusion conformation, may have advantages as candidate RSV vaccines.",2016 Jul 27,"['Boyington, Jeffrey C.', 'Joyce, M. Gordon', 'Sastry, Mallika', 'Stewart-Jones, Guillaume B. E.', 'Chen, Man', 'Kong, Wing-Pui', 'Ngwuta, Joan O.', 'Thomas, Paul V.', 'Tsybovsky, Yaroslav', 'Yang, Yongping', 'Zhang, Baoshan', 'Chen, Lei', 'Druz, Aliaksandr', 'Georgiev, Ivelin S.', 'Ko, Kiyoon', 'Zhou, Tongqing', 'Mascola, John R.', 'Graham, Barney S.', 'Kwong, Peter D.']",PLoS One,,,False
a48482a6bd5e78f140777702151cffe852ea5f1e,PMC,Genome-Wide Analysis of Codon Usage Bias in Epichloë festucae,http://dx.doi.org/10.3390/ijms17071138,PMC4964511,27428961,CC BY,"Analysis of codon usage data has both practical and theoretical applications in understanding the basics of molecular biology. Differences in codon usage patterns among genes reflect variations in local base compositional biases and the intensity of natural selection. Recently, there have been several reports related to codon usage in fungi, but little is known about codon usage bias in Epichloë endophytes. The present study aimed to assess codon usage patterns and biases in 4870 sequences from Epichloë festucae, which may be helpful in revealing the constraint factors such as mutation or selection pressure and improving the bioreactor on the cloning, expression, and characterization of some special genes. The GC content with 56.41% is higher than the AT content (43.59%) in E. festucae. The results of neutrality and effective number of codons plot analyses showed that both mutational bias and natural selection play roles in shaping codon usage in this species. We found that gene length is strongly correlated with codon usage and may contribute to the codon usage patterns observed in genes. Nucleotide composition and gene expression levels also shape codon usage bias in E. festucae. E. festucae exhibits codon usage bias based on the relative synonymous codon usage (RSCU) values of 61 sense codons, with 25 codons showing an RSCU larger than 1. In addition, we identified 27 optimal codons that end in a G or C.",2016 Jul 15,"['Li, Xiuzhang', 'Song, Hui', 'Kuang, Yu', 'Chen, Shuihong', 'Tian, Pei', 'Li, Chunjie', 'Nan, Zhibiao']",Int J Mol Sci,,,True
c1cd72dfc8c71714d7751a0b9820f8f8e0ee3756,PMC,Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses,http://dx.doi.org/10.1074/jbc.M116.736660,PMC4965583,27288409,CC BY,"To determine the effectiveness of immunization strategies used in therapeutic antibody or vaccine development, it is critical to assess the quality of immunization-induced polyclonal antibody responses. Here, we developed a workflow that uses sensitive methods to quantitatively and qualitatively assess immune responses against foreign antigens with regard to antibody binding affinity and epitope diversity. The application of such detailed assessments throughout an immunization campaign can significantly reduce the resources required to generate highly specific antibodies. Our workflow consists of the following two steps: 1) the use of surface plasmon resonance to quantify antigen-specific antibodies and evaluate their apparent binding affinities, and 2) the recovery of serum IgGs using an automated small scale purification system, followed by the determination of their epitope diversity using hydrogen deuterium exchange coupled with mass spectrometry. We showed that these methods were sensitive enough to detect antigen-specific IgGs in the nanogram/μl range and that they provided information for differentiating the antibody responses of the various immunized animals that could not be obtained by conventional methods. We also showed that this workflow can guide the selection of an animal that produces high affinity antibodies with a desired epitope coverage profile, resulting in the generation of potential therapeutic monoclonal antibody clones with desirable functional profiles. We postulate that this workflow will be an important tool in the development of effective vaccines to combat the highly sophisticated evasion mechanisms of pathogens.",2016 Jul 29,"['Yang, Danlin', 'Frego, Lee', 'Lasaro, Marcio', 'Truncali, Kristopher', 'Kroe-Barrett, Rachel', 'Singh, Sanjaya']",J Biol Chem,,,True
a52fd1386e8a463e46bde0e66125bfd826a64f56,PMC,Ebola virus disease and critical illness,http://dx.doi.org/10.1186/s13054-016-1325-2,PMC4965892,27468829,CC BY,"As of 20 May 2016 there have been 28,646 cases and 11,323 deaths resulting from the West African Ebola virus disease (EVD) outbreak reported to the World Health Organization. There continue to be sporadic flare-ups of EVD cases in West Africa. EVD presentation is nonspecific and characterized initially by onset of fatigue, myalgias, arthralgias, headache, and fever; this is followed several days later by anorexia, nausea, vomiting, diarrhea, and abdominal pain. Anorexia and gastrointestinal losses lead to dehydration, electrolyte abnormalities, and metabolic acidosis, and, in some patients, acute kidney injury. Hypoxia and ventilation failure occurs most often with severe illness and may be exacerbated by substantial fluid requirements for intravascular volume repletion and some degree of systemic capillary leak. Although minor bleeding manifestations are common, hypovolemic and septic shock complicated by multisystem organ dysfunction appear the most frequent causes of death. Males and females have been equally affected, with children (0–14 years of age) accounting for 19 %, young adults (15–44 years) 58 %, and older adults (≥45 years) 23 % of reported cases. While the current case fatality proportion in West Africa is approximately 40 %, it has varied substantially over time (highest near the outbreak onset) according to available resources (40–90 % mortality in West Africa compared to under 20 % in Western Europe and the USA), by age (near universal among neonates and high among older adults), and by Ebola viral load at admission. While there is no Ebola virus-specific therapy proven to be effective in clinical trials, mortality has been dramatically lower among EVD patients managed with supportive intensive care in highly resourced settings, allowing for the avoidance of hypovolemia, correction of electrolyte and metabolic abnormalities, and the provision of oxygen, ventilation, vasopressors, and dialysis when indicated. This experience emphasizes that, in addition to evaluating specific medical treatments, improving the global capacity to provide supportive critical care to patients with EVD may be the greatest opportunity to improve patient outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1325-2) contains supplementary material, which is available to authorized users.",2016 Jul 29,"['Leligdowicz, Aleksandra', 'Fischer, William A.', 'Uyeki, Timothy M.', 'Fletcher, Thomas E.', 'Adhikari, Neill K. J.', 'Portella, Gina', 'Lamontagne, Francois', 'Clement, Christophe', 'Jacob, Shevin T.', 'Rubinson, Lewis', 'Vanderschuren, Abel', 'Hajek, Jan', 'Murthy, Srinivas', 'Ferri, Mauricio', 'Crozier, Ian', 'Ibrahima, Elhadj', 'Lamah, Marie-Claire', 'Schieffelin, John S.', 'Brett-Major, David', 'Bausch, Daniel G.', 'Shindo, Nikki', 'Chan, Adrienne K.', 'O’Dempsey, Tim', 'Mishra, Sharmistha', 'Jacobs, Michael', 'Dickson, Stuart', 'Lyon, G. Marshall', 'Fowler, Robert A.']",Crit Care,,,True
6b05be390f36231b7e3a06bc30979536eda0ee6e,PMC,Human Rhinovirus B and C Genomes from Rural Coastal Kenya,http://dx.doi.org/10.1128/genomeA.00751-16,PMC4966474,27469941,CC BY,Primer-independent agnostic deep sequencing was used to generate three human rhinovirus (HRV) B genomes and one HRV C genome from samples collected in a household respiratory survey in rural coastal Kenya. The study provides the first rhinovirus genomes from Kenya and will help improve the sensitivity of local molecular diagnostics.,2016 Jul 28,"['Agoti, Charles N.', 'Kiyuka, Patience K.', 'Kamau, Everlyn', 'Munywoki, Patrick K.', 'Bett, Anne', 'van der Hoek, Lia', 'Kellam, Paul', 'Nokes, D. James', 'Cotten, Matthew']",Genome Announc,,,True
ac793b3e925f08bf9fac41b70e5c9a61d1f37e39,PMC,"The Effects of an Online Mind-Body Training Program on Stress, Coping Strategies, Emotional Intelligence, Resilience and Psychological State",http://dx.doi.org/10.1371/journal.pone.0159841,PMC4968838,27479499,CC BY,"The goal of this study was to evaluate the effects of an online mind-body training (MBT) program on participants’ stress, anger, coping strategies, emotional intelligence, resilience, and positive and negative affect. Forty-two healthy women participated in an online MBT program for approximately 8–10 minutes a day for 8 weeks; a control group of 45 healthy women did not participate in the program. Self-report psychological questionnaires were administered before the beginning of the program and at 4 and 8 weeks following its onset. Data from the MBT group and the control group were compared using repeated measures ANOVA and Student’s t-tests. Significant time x group interaction effects were found with respect to stress, coping strategies, anger, emotional intelligence, negative affect and resilience. These results demonstrate beneficial effects of the online MBT program and significant improvements in the psychological capabilities of participants compared with the control group. The effects of online MBT program were similar with those of the previous offline MBT in psychological aspects, suggesting further studies for neuroscientific evidence related stress and emotion of online MBT effects.",2016 Aug 1,"['Jung, Ye-Ha', 'Ha, Tae Min', 'Oh, Chang Young', 'Lee, UI Soon', 'Jang, Joon Hwan', 'Kim, Jungwon', 'Park, Jae-Oh', 'Kang, Do-Hyung']",PLoS One,,,True
19e45f3e51ee8f9151f7f3e901b2a579366abfd0,PMC,Zika Virus: Where Is the Treatment?,http://dx.doi.org/10.1007/s40506-016-0083-7,PMC4969322,27547128,CC BY,,2016 Jul 8,"['Mumtaz, Noreen', 'van Kampen, Jeroen J. A.', 'Reusken, Chantal B. E. M.', 'Boucher, Charles A. B.', 'Koopmans, Marion P. G.']",Curr Treat Options Infect Dis,,,True
fc151568de57c0456578757131c3b49b86286b3c,PMC,"Inhibition of RNA Helicases of ssRNA(+) Virus Belonging to Flaviviridae, Coronaviridae and Picornaviridae Families",http://dx.doi.org/10.1155/2011/213135,PMC4970650,27516903,CC BY,"Many viral pathogens encode the motor proteins named RNA helicases which display various functions in genome replication. General strategies to design specific and selective drugs targeting helicase for the treatment of viral infections could act via one or more of the following mechanisms: inhibition of the NTPase activity, by interferences with ATP binding and therefore by limiting the energy required for the unwinding and translocation, or by allosteric mechanism and therefore by stabilizing the conformation of the enzyme in low helicase activity state; inhibition of nucleic acids binding to the helicase; inhibition of coupling of ATP hydrolysis to unwinding; inhibition of unwinding by sterically blocking helicase translocation. Recently, by in vitro screening studies, it has been reported that several benzotriazole, imidazole, imidazodiazepine, phenothiazine, quinoline, anthracycline, triphenylmethane, tropolone, pyrrole, acridone, small peptide, and Bananin derivatives are endowed with helicase inhibition of pathogen viruses belonging to Flaviviridae, Coronaviridae, and Picornaviridae families.",2011 Nov 14,"['Briguglio, Irene', 'Piras, Sandra', 'Corona, Paola', 'Carta, Antonio']",Int J Med Chem,,,True
6a0f2ecf39a72ca6067517375a485d98b308e2aa,PMC,Pains and Gains from China's Experiences with Emerging Epidemics: From SARS to H7N9,http://dx.doi.org/10.1155/2016/5717108,PMC4971293,27525272,CC BY,"Over the recent decades, China experienced several emerging virus outbreaks including those caused by the severe acute respiratory syndrome- (SARS-) coronavirus (Cov), H5N1 virus, and H7N9 virus. The SARS tragedy revealed faults in China's infectious disease prevention system, propelling the Chinese government to enact reforms that enabled better combating of the subsequent H1N1 and H7N9 avian flu epidemics. The system is buttressed by three fundamental, mutually reinforcing components: (1) enduring government administration reforms, including legislation establishing a unified public health emergency management system; (2) prioritized funding for biotechnology and biomedicine industrialization, especially in the areas of pathogen identification, drug production, and the development of vaccines and diagnostics; and (3) increasing investment for public health and establishment of a rapid-response infectious diseases prevention and control system. China is now using its hard-gained experience to support the fight against Ebola in Africa and the Middle East Respiratory Syndrome in its own country.",2016 Jul 20,"['Wei, Pengfei', 'Cai, Zelang', 'Hua, Jinwen', 'Yu, Weijia', 'Chen, Jiajie', 'Kang, Kang', 'Qiu, Congling', 'Ye, Lanlan', 'Hu, Jiayun', 'Ji, Kunmei']",Biomed Res Int,,,True
7c53b0536ccc6dd11ad7de4f55c0baa934f38763,PMC,Astrovirus VA1 identified by next-generation sequencing in a nasopharyngeal specimen of a febrile Tanzanian child with acute respiratory disease of unknown etiology,http://dx.doi.org/10.1038/emi.2016.67,PMC4972905,27381218,CC BY,,2016 Jul 6,"['Cordey, Samuel', 'Brito, Francisco', 'Vu, Diem-Lan', 'Turin, Lara', 'Kilowoko, Mary', 'Kyungu, Esther', 'Genton, Blaise', 'Zdobnov, Evgeny M', ""D'Acremont, Valérie"", 'Kaiser, Laurent']",Emerg Microbes Infect,,,True
17334b138ba80214847f144ebc57ce27ff9c23cf,PMC,Pulmonary melanoma and “crazy paving” patterns in chest images: a case report and literature review,http://dx.doi.org/10.1186/s12885-016-2630-5,PMC4973081,27488496,CC BY,"BACKGROUND: In the lung, melanoma is mostly arranged as patterns of multiple nodules, solitary nodules, or miliary invasions. Very rarely, it also displays a “crazy paving” pattern (also described as a “paving stone,” “flagstone,” or “slabstone” pattern), which is rarer still in discrete bilateral nodules. This pattern is considered to be caused by pulmonary alveolar proteinosis, but its association with various diseases is unclear. CASE PRESENTATION: A 60-year-old man was diagnosed with pulmonary melanoma. Computed tomography revealed discrete bilateral nodules surrounded by a “paving” pattern. A literature review found more than 40 types of diseases that have presented with “paving” patterns in the lung—predominantly pulmonary alveolar proteinosis, viral pneumonia, exogenous lipoid pneumonia, bacterial pneumonia, pulmonary alveolar microlithiasis, interstitial pneumonia, ARDS, squalene aspiration pneumonia, radiation pneumonitis, drug-induced pneumonitis, pulmonary leptospirosis, pulmonary hemorrhage, and pulmonary nocardiosis. CONCLUSIONS: We describe the first case of pulmonary melanoma in the form of discrete bilateral nodules accompanied with a computed tomography paving pattern. Although pulmonary paving patterns are rare, more than 40 diseases reportedly display them; clinicians should consider melanoma of the lung in differential diagnoses for patients who show such a pattern.",2016 Aug 3,"['Feng, Yikuan', 'Zhao, Jianping', 'Yang, Qun', 'Xiong, Weining', 'Zhen, Guohua', 'Xu, Yongjian', 'Zhang, Zhenxiang', 'Zhang, Huilan']",BMC Cancer,,,True
913e8bcf134a8415f7aa9d3285e15e1425a60d26,PMC,Tear biomarkers for keratoconus,http://dx.doi.org/10.1186/s40662-016-0051-9,PMC4973115,27493978,CC BY,"Keratoconus is a progressive corneal thinning, ectatic condition, which affects vision. Recent advances in corneal topography measurements has helped advance proper diagnosis of this condition and increased research and clinical interests in the disease etiopathogenesis. Considerable progress has been achieved in understanding the progression of the disease and tear fluid has played a major role in the progress. This review discusses the importance of tear fluid as a source of biomarker for keratoconus and how advances in technology have helped map the complexity of tears and thereby molecular readouts of the disease. Expanding knowledge of the tear proteome, lipidome and metabolome opened up new avenues to study keratoconus and to identify probable prognostic or diagnostic biomarkers for the disease. A multidimensional approach of analyzing tear fluid of patients layering on proteomics, lipidomics and metabolomics is necessary in effectively decoding keratoconus and thereby identifying targets for its treatment.",2016 Aug 4,"['Nishtala, Krishnatej', 'Pahuja, Natasha', 'Shetty, Rohit', 'Nuijts, Rudy M. M. A.', 'Ghosh, Arkasubhra']",Eye Vis (Lond),,,True
46605a285131acb104ba6ed5a7b15a23839bdb49,PMC,Transmission or Within-Host Dynamics Driving Pulses of Zoonotic Viruses in Reservoir–Host Populations,http://dx.doi.org/10.1371/journal.pntd.0004796,PMC4973921,27489944,CC0,"Progress in combatting zoonoses that emerge from wildlife is often constrained by limited knowledge of the biology of pathogens within reservoir hosts. We focus on the host–pathogen dynamics of four emerging viruses associated with bats: Hendra, Nipah, Ebola, and Marburg viruses. Spillover of bat infections to humans and domestic animals often coincides with pulses of viral excretion within bat populations, but the mechanisms driving such pulses are unclear. Three hypotheses dominate current research on these emerging bat infections. First, pulses of viral excretion could reflect seasonal epidemic cycles driven by natural variations in population densities and contact rates among hosts. If lifelong immunity follows recovery, viruses may disappear locally but persist globally through migration; in either case, new outbreaks occur once births replenish the susceptible pool. Second, epidemic cycles could be the result of waning immunity within bats, allowing local circulation of viruses through oscillating herd immunity. Third, pulses could be generated by episodic shedding from persistently infected bats through a combination of physiological and ecological factors. The three scenarios can yield similar patterns in epidemiological surveys, but strategies to predict or manage spillover risk resulting from each scenario will be different. We outline an agenda for research on viruses emerging from bats that would allow for differentiation among the scenarios and inform development of evidence-based interventions to limit threats to human and animal health. These concepts and methods are applicable to a wide range of pathogens that affect humans, domestic animals, and wildlife.",2016 Aug 4,"['Plowright, Raina K.', 'Peel, Alison J.', 'Streicker, Daniel G.', 'Gilbert, Amy T.', 'McCallum, Hamish', 'Wood, James', 'Baker, Michelle L.', 'Restif, Olivier']",PLoS Negl Trop Dis,,,True
d2b714f43fa6302301a1aa7d282de555f71024b2,PMC,Germinal Center B Cell and T Follicular Helper Cell Responses to Viral Vector and Protein-in-Adjuvant Vaccines,http://dx.doi.org/10.4049/jimmunol.1502472,PMC4974488,27412417,CC BY,"There is great interest in the development of Ab-inducing subunit vaccines targeting infections, including HIV, malaria, and Ebola. We previously reported that adenovirus vectored vaccines are potent in priming Ab responses, but uncertainty remains regarding the optimal approach for induction of humoral immune responses. In this study, using OVA as a model Ag, we assessed the magnitude of the primary and anamnestic Ag–specific IgG responses of mice to four clinically relevant vaccine formulations: replication-deficient adenovirus; modified vaccinia Ankara (a poxvirus); protein with alum; and protein in the squalene oil-in-water adjuvant Addavax. We then used flow cytometric assays capable of measuring total and Ag-specific germinal center (GC) B cell and follicular Th cell responses to compare the induction of these responses by the different formulations. We report that adenovirus vectored vaccines induce Ag insert–specific GC B cell and Ab responses of a magnitude comparable to those induced by a potent protein/squalene oil-in-water formulation whereas—despite a robust overall GC response—the insert-specific GC B cell and Ab responses induced by modified vaccinia Ankara were extremely weak. Ag-specific follicular Th cell responses to adenovirus vectored vaccines exceeded those induced by other platforms at day 7 after immunization. We found little evidence that innate immune activation by adenovirus may act as an adjuvant in such a manner that the humoral response to a recombinant protein may be enhanced by coadministering with an adenovirus lacking a transgene of interest. Overall, these studies provide further support for the use of replication-deficient adenoviruses to induce humoral responses.",2016 Aug 15,"['Wang, Chuan', 'Hart, Matthew', 'Chui, Cecilia', 'Ajuogu, Augustine', 'Brian, Iona J.', 'de Cassan, Simone C.', 'Borrow, Persephone', 'Draper, Simon J.', 'Douglas, Alexander D.']",J Immunol,,,True
649b2f2aba88c512775160f197a250e51ac8bc14,PMC,Replication-Competent Influenza A Viruses Expressing Reporter Genes,http://dx.doi.org/10.3390/v8070179,PMC4974514,27347991,CC BY,"Influenza A viruses (IAV) cause annual seasonal human respiratory disease epidemics. In addition, IAV have been implicated in occasional pandemics with inordinate health and economic consequences. Studying IAV, in vitro or in vivo, requires the use of laborious secondary methodologies to identify virus-infected cells. To circumvent this requirement, replication-competent IAV expressing an easily traceable reporter protein can be used. Here we discuss the development and applications of recombinant replication-competent IAV harboring diverse fluorescent or bioluminescent reporter genes in different locations of the viral genome. These viruses have been employed for in vitro and in vivo studies, such as the screening of neutralizing antibodies or antiviral compounds, the identification of host factors involved in viral replication, cell tropism, the development of vaccines, or the assessment of viral infection dynamics. In summary, reporter-expressing, replicating-competent IAV represent a powerful tool for the study of IAV both in vitro and in vivo.",2016 Jun 23,"['Breen, Michael', 'Nogales, Aitor', 'Baker, Steven F.', 'Martínez-Sobrido, Luis']",Viruses,,,True
e3fe1b272c977754c55719ab93e90ecb0b9472d5,PMC,Who Regulates Whom? An Overview of RNA Granules and Viral Infections,http://dx.doi.org/10.3390/v8070180,PMC4974515,27367717,CC BY,"After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis) and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs), which are translationally silent sites of RNA triage and processing bodies (PBs), which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs).",2016 Jun 28,"['Poblete-Durán, Natalia', 'Prades-Pérez, Yara', 'Vera-Otarola, Jorge', 'Soto-Rifo, Ricardo', 'Valiente-Echeverría, Fernando']",Viruses,,,True
a51a3f793ea6a59523eff2c0fe6555b729840084,PMC,Newcastle Disease Virus as a Vaccine Vector for Development of Human and Veterinary Vaccines,http://dx.doi.org/10.3390/v8070183,PMC4974518,27384578,CC BY,"Viral vaccine vectors have shown to be effective in inducing a robust immune response against the vaccine antigen. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising vaccine vector against human and veterinary pathogens. Avirulent NDV strains LaSota and B1 have long track records of safety and efficacy. Therefore, use of these strains as vaccine vectors is highly safe in avian and non-avian species. NDV replicates efficiently in the respiratory track of the host and induces strong local and systemic immune responses against the foreign antigen. As a vaccine vector, NDV can accommodate foreign sequences with a good degree of stability and as a RNA virus, there is limited possibility for recombination with host cell DNA. Using NDV as a vaccine vector in humans offers several advantages over other viral vaccine vectors. NDV is safe in humans due to host range restriction and there is no pre-existing antibody to NDV in the human population. NDV is antigenically distinct from common human pathogens. NDV replicates to high titer in a cell line acceptable for human vaccine development. Therefore, NDV is an attractive vaccine vector for human pathogens for which vaccines are currently not available. NDV is also an attractive vaccine vector for animal pathogens.",2016 Jul 4,"['Kim, Shin-Hee', 'Samal, Siba K.']",Viruses,,,True
5fc3eedb09f3b7624fec7d2b9afedfffbab47a21,PMC,Regulation of Stress Responses and Translational Control by Coronavirus,http://dx.doi.org/10.3390/v8070184,PMC4974519,27384577,CC BY,"Similar to other viruses, coronavirus infection triggers cellular stress responses in infected host cells. The close association of coronavirus replication with the endoplasmic reticulum (ER) results in the ER stress responses, which impose a challenge to the viruses. Viruses, in turn, have come up with various mechanisms to block or subvert these responses. One of the ER stress responses is inhibition of the global protein synthesis to reduce the amount of unfolded proteins inside the ER lumen. Viruses have evolved the capacity to overcome the protein translation shutoff to ensure viral protein production. Here, we review the strategies exploited by coronavirus to modulate cellular stress response pathways. The involvement of coronavirus-induced stress responses and translational control in viral pathogenesis will also be briefly discussed.",2016 Jul 4,"['Fung, To Sing', 'Liao, Ying', 'Liu, Ding Xiang']",Viruses,,,True
467143e07e3d6ec8a0617a5bdee446ab2c63581c,PMC,"The Role of Phlebovirus Glycoproteins in Viral Entry, Assembly and Release",http://dx.doi.org/10.3390/v8070202,PMC4974537,27455305,CC BY,"Bunyaviruses are enveloped viruses with a tripartite RNA genome that can pose a serious threat to animal and human health. Members of the Phlebovirus genus of the family Bunyaviridae are transmitted by mosquitos and ticks to humans and include highly pathogenic agents like Rift Valley fever virus (RVFV) and severe fever with thrombocytopenia syndrome virus (SFTSV) as well as viruses that do not cause disease in humans, like Uukuniemi virus (UUKV). Phleboviruses and other bunyaviruses use their envelope proteins, Gn and Gc, for entry into target cells and for assembly of progeny particles in infected cells. Thus, binding of Gn and Gc to cell surface factors promotes viral attachment and uptake into cells and exposure to endosomal low pH induces Gc-driven fusion of the viral and the vesicle membranes. Moreover, Gn and Gc facilitate virion incorporation of the viral genome via their intracellular domains and Gn and Gc interactions allow the formation of a highly ordered glycoprotein lattice on the virion surface. Studies conducted in the last decade provided important insights into the configuration of phlebovirus Gn and Gc proteins in the viral membrane, the cellular factors used by phleboviruses for entry and the mechanisms employed by phlebovirus Gc proteins for membrane fusion. Here, we will review our knowledge on the glycoprotein biogenesis and the role of Gn and Gc proteins in the phlebovirus replication cycle.",2016 Jul 21,"['Spiegel, Martin', 'Plegge, Teresa', 'Pöhlmann, Stefan']",Viruses,,,True
33bfc254b350a34f254ea0c56d349ddae719048b,PMC,Local Innate Responses to TLR Ligands in the Chicken Trachea,http://dx.doi.org/10.3390/v8070207,PMC4974541,27455308,CC BY,"The chicken upper respiratory tract is the portal of entry for respiratory pathogens, such as avian influenza virus (AIV). The presence of microorganisms is sensed by pathogen recognition receptors (such as Toll-like receptors (TLRs)) of the innate immune defenses. Innate responses are essential for subsequent induction of potent adaptive immune responses, but little information is available about innate antiviral responses of the chicken trachea. We hypothesized that TLR ligands induce innate antiviral responses in the chicken trachea. Tracheal organ cultures (TOC) were used to investigate localized innate responses to TLR ligands. Expression of candidate genes, which play a role in antiviral responses, was quantified. To confirm the antiviral responses of stimulated TOC, chicken macrophages were treated with supernatants from stimulated TOC, prior to infection with AIV. The results demonstrated that TLR ligands induced the expression of pro-inflammatory cytokines, type I interferons and interferon stimulated genes in the chicken trachea. In conclusion, TLR ligands induce functional antiviral responses in the chicken trachea, which may act against some pathogens, such as AIV.",2016 Jul 22,"['Barjesteh, Neda', 'Alkie, Tamiru Negash', 'Hodgins, Douglas C.', 'Nagy, Éva', 'Sharif, Shayan']",Viruses,,,True
9a13ccd6be3536af404c25e748c34eac997c5d16,PMC,Expression of Cystic Fibrosis Transmembrane Conductance Regulator in Ganglia of Human Gastrointestinal Tract,http://dx.doi.org/10.1038/srep30926,PMC4974654,27491544,CC BY,"CF is caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) which is an anion selective transmembrane ion channel that mainly regulates chloride transport, expressed in the epithelia of various organs. Recently, we have demonstrated CFTR expression in the brain, the spinal cord and the sympathetic ganglia. This study aims to investigate the expression and distribution of CFTR in the ganglia of the human gastrointestinal tract. Fresh tissue and formalin-fixed paraffin-embedded normal gastrointestinal tract samples were collected from eleven surgical patients and five autopsy cases. Immunohistochemistry, in situ hybridization, laser-assisted microdissection and nested reverse transcriptase polymerase chain reaction were performed. Expression of CFTR protein and mRNA was detected in neurons of the ganglia of all segments of the human gastrointestinal tract examined, including the stomach, duodenum, jejunum, ileum, cecum, appendix, colon and rectum. The extensive expression of CFTR in the enteric ganglia suggests that CFTR may play a role in the physiology of the innervation of the gastro-intestinal tract. The presence of dysfunctional CFTRs in enteric ganglia could, to a certain extent, explain the gastrointestinal symptoms frequently experienced by CF patients.",2016 Aug 5,"['Xue, Ruiqi', 'Gu, Huan', 'Qiu, Yamei', 'Guo, Yong', 'Korteweg, Christine', 'Huang, Jin', 'Gu, Jiang']",Sci Rep,,,True
1329ea9b040bdc8af7c30f7ba4b5755e352deae8,PMC,Occurrence and sequence analysis of porcine deltacoronaviruses in southern China,http://dx.doi.org/10.1186/s12985-016-0591-6,PMC4974758,27496131,CC BY,"BACKGROUND: Following the initial isolation of porcine deltacoronavirus (PDCoV) from pigs with diarrheal disease in the United States in 2014, the virus has been detected on swine farms in some provinces of China. To date, little is known about the molecular epidemiology of PDCoV in southern China where major swine production is operated. RESULTS: To investigate the prevalence of PDCoV in this region and compare its activity to other enteric disease of swine caused by porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis coronavirus (TGEV), and porcine rotavirus group C (Rota C), 390 fecal samples were collected from swine of various ages from 15 swine farms with reported diarrhea. Fecal samples were tested by reverse transcription-PCR (RT-PCR) that targeted PDCoV, PEDV, TGEV, and Rota C, respectively. PDCoV was detected exclusively from nursing piglets with an overall prevalence of approximate 1.28 % (5/390), not in suckling and fattening piglets. Interestingly, all of PDCoV-positive samples were from 2015 rather than 2012–2014. Despite a low detection rate, PDCoV emerged in each province/region of southern China. In addition, compared to TGEV (1.54 %, 5/390) or Rota C (1.28 %, 6/390), there were highly detection rates of PEDV (22.6 %, 88/390) in those samples. Notably, all five PDCoV-positive piglets were co-infected by PEDV. Furthermore, phylogenetic analysis of spike (S) and nucleocapsid (N) gene sequences of PDCoVs revealed that currently circulating PDCoVs in southern China were more closely related to other Chinese strains of PDCoVs than to those reported in United States, South Korea and Thailand. CONCLUSIONS: This study demonstrated that PDCoV was present in southern China despite the low prevalence, and supported an evolutionary theory of geographical clustering of PDCoVs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0591-6) contains supplementary material, which is available to authorized users.",2016 Aug 5,"['Zhai, Shao-Lun', 'Wei, Wen-Kang', 'Li, Xiao-Peng', 'Wen, Xiao-Hui', 'Zhou, Xia', 'Zhang, He', 'Lv, Dian-Hong', 'Li, Feng', 'Wang, Dan']",Virol J,,,True
db0b1c57b81cdb3facc4177cf7f6a208eab730b9,PMC,Osteopontin Fragments with Intact Thrombin-Sensitive Site Circulate in Cervical Cancer Patients,http://dx.doi.org/10.1371/journal.pone.0160412,PMC4975440,27494141,CC0,"We investigated whether circulating osteopontin (OPN) could be used as a biomarker for cervical cancer. We employed a monoclonal antibody (mAb 659) specific for the unique and intact thrombin-sensitive site in OPN using an inhibition ELISA. We found significantly higher levels of OPN in 33 cervical cancer patients in both the plasma (mean +/- SD, 612 +/- 106 ng/mL) and serum (424 +/- 121 ng/mL) compared to healthy subjects [409 +/- 56 ng/mL, from 31 plasma samples (P < 0.0001), and 314 +/- 98 ng/mL, from 32 serum samples (P = 0.0002), respectively]. Similar results were obtained when the plasma from a bigger group (147 individuals) of cervical cancer patients (560 +/- 211 ng/mL) were compared with the same plasma samples of the healthy individuals (P = 0.0014). More significantly, the OPN level was highest in stage III-IV disease (614 +/- 210 ng/mL, from 52 individuals; P = 0.0001) and least and non-discriminatory in stage I (473 +/- 110 ng/mL, from 40 individuals; P = 0.5318). No such discrimination was found when a mAb of a different specificity (mAb 446) was used in a similar inhibition ELISA to compare the two groups in the first study; a commercial capture ELISA also failed. The possibility that the target epitope recognized by the antibody probe in these assays was absent from the circulating OPN due to protein truncation was supported by gel fractionation of the OPN found in patients’ plasma: 60–64 kDa fragments were found instead of the presumably full-length OPN (68 kDa) seen in healthy people. How these fragments are generated and what possible role they play in cancer biology remain interesting questions.",2016 Aug 5,"['Leung, Danny T. M.', 'Lim, Pak-Leong', 'Cheung, Tak-Hong', 'Wong, Raymond R. Y.', 'Yim, So-Fan', 'Ng, Margaret H. L.', 'Tam, Frankie C. H.', 'Chung, Tony K. H.', 'Wong, Yick-Fu']",PLoS One,,,True
a286c95345592981acce2ffe297605fd083d9fe7,PMC,"Molecular Characterization of the ORF3 and S1 Genes of Porcine Epidemic Diarrhea Virus Non S-INDEL Strains in Seven Regions of China, 2015",http://dx.doi.org/10.1371/journal.pone.0160561,PMC4975444,27494026,CC BY,"In an effort to trace the evolution of porcine epidemic diarrhea virus (PEDV), S1 and ORF3 genes of viruses identified in 41 pig farms from seven regions (North, Northeast, Northwest, Central, East, South West, and South, respectively) of China in 2015 were sequenced and analyzed. Sequence analysis revealed that the 41 ORF3 genes and 29 S1 genes identified in our study exhibited nucleotide homologies of 98.2%–100% and 96.6%–100%, respectively; these two genes exhibited low nucleotide sequence similarities with classical CV777 strain and early Chinese strain LZC. Phylogenetic analysis indicated that the identified PEDV strains belonged to global non S-INDEL strains, and exhibited genetic diversity; S1 gene of the HLJ2015/DP1-1 strain harbored an unique deletion of 12 nucleotides (A(1130)CAACTCCACTG(1141)); while the Chinese PEDV S-INDEL reference strains included two types of the “CV777” S-INDEL as well as the “US” S-INDEL, and all co-circulated with Chinese non S-INDEL strains. Of 29 identified S1 genes, the SS2 epitope (Y(748)SNIGVCK(755)) was highly conserved, while the SS6 epitope (L(764)QDGQVKI(771)) and pAPN receptor-binding region (aa 490–615) exhibited amino substitutions. Nine possible recombination events were identified between the 29 identifed S1 genes and the 3 S1 reference genes from early Chinese PEDV strains. The complete S genes of selected Chinese PEDV field strains (2011–2015) showed 5.18%–6.07% nucleotide divergence, which is far higher than the divergence observed in early Chinese PEDV strains (3.1%) (P<0.05). Our data provide evidence that PEDV non S-INDEL strains with genetic diversities and potential recombination circulate in seven regions of China in 2015; Chinese PEDV S-INDEL strains exhibit genetic diversity and co-circulate with non S-INDEL strains.",2016 Aug 5,"['Wang, Enyu', 'Guo, Donghua', 'Li, Chunqiu', 'Wei, Shan', 'Wang, Zhihui', 'Liu, Qiujin', 'Zhang, Bei', 'Kong, Fanzhi', 'Feng, Li', 'Sun, Dongbo']",PLoS One,,,True
283047560dd3e30f1161338e0f4f2fcc335328f1,PMC,Passive immunization does not provide protection against experimental infection with Mycoplasma haemofelis,http://dx.doi.org/10.1186/s13567-016-0361-x,PMC4975915,27496124,CC BY,"Mycoplasma haemofelis (Mhf) is the most pathogenic feline hemotropic mycoplasma. Cats infected with Mhf that clear bacteremia are protected from Mhf reinfection, but the mechanisms of protective immunity are unresolved. In the present study we investigated whether the passive transfer of antibodies from Mhf-recovered cats to naïve recipient cats provided protection against bacteremia and clinical disease following homologous challenge with Mhf; moreover, we characterized the immune response in the recipient cats. Ten specified pathogen-free (SPF) cats were transfused with pooled plasma from cats that had cleared Mhf bacteremia; five control cats received plasma from naïve SPF cats. After homologous challenge with Mhf, cats were monitored for 100 days using quantitative PCR, hematology, blood biochemistry, Coombs testing, flow cytometry, DnaK ELISA, and red blood cell (RBC) osmotic fragility (OF) measurement. Passively immunized cats were not protected against Mhf infection but, compared to control cats, showed significantly higher RBC OF and B lymphocyte (CD45R/B220(+)) counts and occasionally higher lymphocyte, monocyte and activated CD4(+) T lymphocyte (CD4(+)CD25(+)) counts; they also showed higher bilirubin, total protein and globulin levels compared to those of control cats. At times of peak bacteremia, a decrease in eosinophils and lymphocytes, as well as subsets thereof (B lymphocytes and CD5(+), CD4(+) and CD8(+) T lymphocytes), and an increase in monocytes were particularly significant in the passively immunized cats. In conclusion, passive immunization does not prevent bacteremia and clinical disease following homologous challenge with Mhf, but enhances RBC osmotic fragility and induces a pronounced immune response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0361-x) contains supplementary material, which is available to authorized users.",2016 Aug 5,"['Sugiarto, Sarah', 'Spiri, Andrea M.', 'Riond, Barbara', 'Novacco, Marilisa', 'Oestmann, Angelina', 'de Miranda, Luisa H. Monteiro', 'Meli, Marina L.', 'Boretti, Felicitas S.', 'Hofmann-Lehmann, Regina', 'Willi, Barbara']",Vet Res,,,True
729e5d420ec1a80d31928dc8bb261610a93aa890,PMC,Structure and Function of HLA-A*02-Restricted Hantaan Virus Cytotoxic T-Cell Epitope That Mediates Effective Protective Responses in HLA-A2.1/K(b) Transgenic Mice,http://dx.doi.org/10.3389/fimmu.2016.00298,PMC4976285,27551282,CC BY,"Hantavirus infections cause severe emerging diseases in humans and are associated with high mortality rates; therefore, they have become a global public health concern. Our previous study showed that the CD8(+) T-cell epitope aa129–aa137 (FVVPILLKA, FA9) of the Hantaan virus (HTNV) nucleoprotein (NP), restricted by human leukocyte antigen (HLA)-A*02, induced specific CD8(+) T-cell responses that controlled HTNV infection in humans. However, the in vivo immunogenicity of peptide FA9 and the effect of FA9-specific CD8(+) T-cell immunity remain unclear. Here, based on a detailed structural analysis of the peptide FA9/HLA-A*0201 complex and functional investigations using HLA-A2.1/K(b) transgenic (Tg) mice, we found that the overall structure of the peptide FA9/HLA-A*0201 complex displayed a typical MHC class I fold with Val2 and Ala9 as primary anchor residues and Val3 and Leu7 as secondary anchor residues that allow peptide FA9 to bind tightly with an HLA-A*0201 molecule. Residues in the middle portion of peptide FA9 extruding out of the binding groove may be the sites that allow for recognition by T-cell receptors. Immunization with peptide FA9 in HLA-A2.1/K(b) Tg mice induced FA9-specific cytotoxic T-cell responses characterized by the induction of high expression levels of interferon-γ, tumor necrosis factor-α, granzyme B, and CD107a. In an HTNV challenge trial, significant reductions in the levels of both the antigens and the HTNV RNA loads were observed in the liver, spleen, and kidneys of Tg mice pre-vaccinated with peptide FA9. Thus, our findings highlight the ability of HTNV epitope-specific CD8(+) T-cell immunity to control HTNV and support the possibility that the HTNV-NP FA9 peptide, naturally processed in vivo in an HLA-A*02-restriction manner, may be a good candidate for the development HTNV peptide vaccines.",2016 Aug 8,"['Ma, Ying', 'Cheng, Linfeng', 'Yuan, Bin', 'Zhang, Yusi', 'Zhang, Chunmei', 'Zhang, Yun', 'Tang, Kang', 'Zhuang, Ran', 'Chen, Lihua', 'Yang, Kun', 'Zhang, Fanglin', 'Jin, Boquan']",Front Immunol,,,True
2bf72671f78524129acb86ceef6c598e10c7daa7,PMC,Structure of a Highly Active Cephalopod S-crystallin Mutant: New Molecular Evidence for Evolution from an Active Enzyme into Lens-Refractive Protein,http://dx.doi.org/10.1038/srep31176,PMC4976375,27499004,CC BY,"Crystallins are found widely in animal lenses and have important functions due to their refractive properties. In the coleoid cephalopods, a lens with a graded refractive index provides good vision and is required for survival. Cephalopod S-crystallin is thought to have evolved from glutathione S-transferase (GST) with various homologs differentially expressed in the lens. However, there is no direct structural information that helps to delineate the mechanisms by which S-crystallin could have evolved. Here we report the structural and biochemical characterization of novel S-crystallin-glutathione complex. The 2.35-Å crystal structure of a S-crystallin mutant from Octopus vulgaris reveals an active-site architecture that is different from that of GST. S-crystallin has a preference for glutathione binding, although almost lost its GST enzymatic activity. We’ve also identified four historical mutations that are able to produce a “GST-like” S-crystallin that has regained activity. This protein recapitulates the evolution of S-crystallin from GST. Protein stability studies suggest that S-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with GST-σ, which do not possess this protection. We suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution.",2016 Aug 8,"['Tan, Wei-Hung', 'Cheng, Shu-Chun', 'Liu, Yu-Tung', 'Wu, Cheng-Guo', 'Lin, Min-Han', 'Chen, Chiao-Che', 'Lin, Chao-Hsiung', 'Chou, Chi-Yuan']",Sci Rep,,,True
e9af8ceed4b7a1f1cfbd6adcc0b9bff83b271f5b,PMC,Structure of a Highly Active Cephalopod S-crystallin Mutant: New Molecular Evidence for Evolution from an Active Enzyme into Lens-Refractive Protein,http://dx.doi.org/10.1038/srep31176,PMC4976375,27499004,CC BY,"Crystallins are found widely in animal lenses and have important functions due to their refractive properties. In the coleoid cephalopods, a lens with a graded refractive index provides good vision and is required for survival. Cephalopod S-crystallin is thought to have evolved from glutathione S-transferase (GST) with various homologs differentially expressed in the lens. However, there is no direct structural information that helps to delineate the mechanisms by which S-crystallin could have evolved. Here we report the structural and biochemical characterization of novel S-crystallin-glutathione complex. The 2.35-Å crystal structure of a S-crystallin mutant from Octopus vulgaris reveals an active-site architecture that is different from that of GST. S-crystallin has a preference for glutathione binding, although almost lost its GST enzymatic activity. We’ve also identified four historical mutations that are able to produce a “GST-like” S-crystallin that has regained activity. This protein recapitulates the evolution of S-crystallin from GST. Protein stability studies suggest that S-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with GST-σ, which do not possess this protection. We suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution.",2016 Aug 8,"['Tan, Wei-Hung', 'Cheng, Shu-Chun', 'Liu, Yu-Tung', 'Wu, Cheng-Guo', 'Lin, Min-Han', 'Chen, Chiao-Che', 'Lin, Chao-Hsiung', 'Chou, Chi-Yuan']",Sci Rep,,,False
d9c950cf19a2048596a6e143471fb2d0c009d8f0,PMC,"System effectiveness of detection, brief intervention and refer to treatment for the people with post-traumatic emotional distress by MERS: a case report of community-based proactive intervention in South Korea",http://dx.doi.org/10.1186/s13033-016-0083-5,PMC4976505,27504141,CC BY,"BACKGROUND: Korea has experienced diverse kind of disasters these days. Among them the 2015 middle eastern respiratory syndrome (MERS) outbreak imposed great psychological stress on almost all Korean citizens. Following the MERS outbreak, government is reviewing overall infectious disease management system and prioritizing the establishment of mental health service systems for infectious disease. This study makes suggestions for implementing disaster-related mental health service systems by analyzing the example of Gyeonggi Province, which proactively intervened with residents’ psychological problems caused by the large-scale outbreak of an infectious disease. CASE DESCRIPTION: Mental health service system for MERS victims had the following two parts: a mental health service for people who had been placed in quarantine and a service provided to families of patients who had died or recovered patients. The government of Gyeonggi province, public health centers, regional and local Community Mental Health Centers and the National Center for Crisis Mental Health Management participated in this service system. Among 1221 Gyeonggi people placed in quarantine and who experienced psychological and emotional difficulties, 350 required continuing services; 124 of this group received continuing services. That is, 35 % of people who required psychological intervention received contact from service providers and received the required services. CONCLUSIONS: This study reflects a proactive monitoring system for thousands of people placed under quarantine for the first time in Korea. It is significant that the service utilization rate by a proactive manner, that is the professionals administering it actively approached and contacted people with problems rather than passively providing information was much higher than other general mental health situation in Korea. The core value of public mental health services is adequate public accessibility; it is therefore essential for governments to strengthen their professional competence and establish effective systems. These criteria should also be applied to psychological problems caused by disastrous infectious disease outbreaks.",2016 Aug 8,"['Yoon, Mi-Kyung', 'Kim, Soon-Young', 'Ko, Hye-Sun', 'Lee, Myung-Soo']",Int J Ment Health Syst,,,True
ebf7e1110aa56a3066f9590befe475eb12b3eaa1,PMC,Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity,http://dx.doi.org/10.1371/journal.pone.0160606,PMC4976934,27500954,CC BY,"BACKGROUND: Despite a high burden of respiratory syncytial virus (RSV) infections among children, data on demographic and clinical characteristics of RSV are scarce in low and middle income countries. This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. METHODS: A prospective study among children under two years of age, hospitalized with LRTI was conducted in two referral pediatric hospitals in Ho Chi Minh City, Vietnam, from May 2009 to December 2010. Socio-demographic, clinical data and nasopharyngeal swabs were collected on enrolment and discharge. Multiplex real-time RT-PCR (13 viruses) and quantitative RSV RT-PCR were used to identify viral pathogens, RSV load and subgroups. RESULTS: Among 632 cases, 48% were RSV positive. RSV infections occurred at younger age than three other leading viral infections i.e rhinovirus (RV), metapneumovirus (MPV), parainfluenza virus (PIV-3) and were significantly more frequent in the first 6 months of life. Clinical severity score of RSV infection was significantly higher than PIV-3 but not for RV or MPV. In multivariate analysis, RV infection was significantly associated with severity while RSV infection was not. Among RSV infections, neither viral load nor viral co-infections were significantly associated with severity. Young age and having fever at admission were significantly associated with both RSV and LRTI severity. A shift in RSV subgroup predominance was observed during two consecutive rainy seasons but was not associated with severity. CONCLUSION: We report etiologies, the epidemiological and clinical characteristics of LRTI among hospitalized children under two years of age and risk factors of RSV and LRTI severity.",2016 Aug 8,"['Do, Lien Anh Ha', 'Bryant, Juliet E.', 'Tran, Anh Tuan', 'Nguyen, Bach Hue', 'Tran, Thi Thu Loan', 'Tran, Quynh Huong', 'Vo, Quoc Bao', 'Tran Dac, Nguyen Anh', 'Trinh, Hong Nhien', 'Nguyen, Thi Thanh Hai', 'Le Binh, Bao Tinh', 'Le, Khanh', 'Nguyen, Minh Tien', 'Thai, Quang Tung', 'Vo, Thanh Vu', 'Ngo, Ngoc Quang Minh', 'Dang, Thi Kim Huyen', 'Cao, Ngoc Huong', 'Tran, Thu Van', 'Ho, Lu Viet', 'Farrar, Jeremy', 'de Jong, Menno', 'van Doorn, H. Rogier']",PLoS One,,,True
a65111e0e1a8f26d4789ea6439cae1cfa5b391b8,PMC,A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome,http://dx.doi.org/10.3389/fnhum.2016.00403,PMC4977292,27555815,CC BY,"Owing to the reports of microcephaly as a consistent outcome in the fetuses of pregnant women infected with ZIKV in Brazil, Zika virus (ZIKV)—microcephaly etiomechanistic relationship has recently been implicated. Researchers, however, are still struggling to establish an embryological basis for this interesting causal handcuff. The present study reveals robust evidence in favor of a plausible ZIKV-microcephaly cause-effect liaison. The rationale is based on: (1) sequence homology between ZIKV genome and the response element of an early neural tube developmental marker “retinoic acid” in human DNA and (2) comprehensive similarities between the details of brain defects in ZIKV-microcephaly and retinoic acid embryopathy. Retinoic acid is considered as the earliest factor for regulating anteroposterior axis of neural tube and positioning of structures in developing brain through retinoic acid response elements (RARE) consensus sequence (5′–AGGTCA–3′) in promoter regions of retinoic acid-dependent genes. We screened genomic sequences of already reported virulent ZIKV strains (including those linked to microcephaly) and other viruses available in National Institute of Health genetic sequence database (GenBank) for the RARE consensus repeats and obtained results strongly bolstering our hypothesis that ZIKV strains associated with microcephaly may act through precipitation of dysregulation in retinoic acid-dependent genes by introducing extra stretches of RARE consensus sequence repeats in the genome of developing brain cells. Additional support to our hypothesis comes from our findings that screening of other viruses for RARE consensus sequence repeats is positive only for those known to display neurotropism and cause fetal brain defects (for which maternal-fetal transmission during developing stage may be required). The numbers of RARE sequence repeats appeared to match with the virulence of screened positive viruses. Although, bioinformatic evidence and embryological features are in favor of our hypothesis, additional studies including animal models are warranted to validate our proposition. Such studies are likely to unfold ZIKV-microcephaly association and may help in devising methods to combat it.",2016 Aug 9,"['Kumar, Ashutosh', 'Singh, Himanshu N.', 'Pareek, Vikas', 'Raza, Khursheed', 'Dantham, Subrahamanyam', 'Kumar, Pavan', 'Mochan, Sankat', 'Faiq, Muneeb A.']",Front Hum Neurosci,,,True
a4ee11dba58a0b0c6566a1fac060b4329bcdc8cd,PMC,Study and interest of cellular load in respiratory samples for the optimization of molecular virological diagnosis in clinical practice,http://dx.doi.org/10.1186/s12879-016-1730-9,PMC4977610,27503120,CC BY,"BACKGROUND: Respiratory viral diagnosis of upper respiratory tract infections has largely developed through multiplex molecular techniques. Although the sensitivity of different types of upper respiratory tract samples seems to be correlated to the number of sampled cells, this link remains largely unexplored. METHODS: Our study included 800 upper respiratory tract specimens of which 400 negative and 400 positive for viral detection in multiplex PCR. All samples were selected and matched for age in these 2 groups. For the positive group, samples were selected for the detected viral species. RESULTS: Among the factors influencing the cellularity were the type of sample (p < 0.0001); patient age (p < 0.001); viral positive or negative nature of the sample (p = 0.002); and, for the positive samples, the number of viral targets detected (0.004 < p < 0.049) and viral species. CONCLUSION: The cellular load of upper respiratory samples is multifactorial and occurs for many in the sensitivity of molecular detection. However it was not possible to determine a minimum cellularity threshold allowing molecular viral detection. The differences according to the type of virus remain to be studied on a larger scale.",2016 Aug 9,"['Bonnin, Paul', 'Miszczak, Fabien', 'Kin, Nathalie', 'Resa, Cecile', 'Dina, Julia', 'Gouarin, Stephanie', 'Viron, Florent', 'Morello, Remy', 'Vabret, Astrid']",BMC Infect Dis,,,True
2c7f8c9a78ec06b29ea61f2dd02730d2c3af1cfb,PMC,An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens,http://dx.doi.org/10.1371/journal.ppat.1005804,PMC4978498,27505057,CC0,"The healthy lung maintains a steady state of immune readiness to rapidly respond to injury from invaders. Integrins are important for setting the parameters of this resting state, particularly the epithelial-restricted αVβ6 integrin, which is upregulated during injury. Once expressed, αVβ6 moderates acute lung injury (ALI) through as yet undefined molecular mechanisms. We show that the upregulation of β6 during influenza infection is involved in disease pathogenesis. β6-deficient mice (β6 KO) have increased survival during influenza infection likely due to the limited viral spread into the alveolar spaces leading to reduced ALI. Although the β6 KO have morphologically normal lungs, they harbor constitutively activated lung CD11b(+) alveolar macrophages (AM) and elevated type I IFN signaling activity, which we traced to the loss of β6-activated transforming growth factor-β (TGF-β). Administration of exogenous TGF-β to β6 KO mice leads to reduced numbers of CD11b(+) AMs, decreased type I IFN signaling activity and loss of the protective phenotype during influenza infection. Protection extended to other respiratory pathogens such as Sendai virus and bacterial pneumonia. Our studies demonstrate that the loss of one epithelial protein, αVβ6 integrin, can alter the lung microenvironment during both homeostasis and respiratory infection leading to reduced lung injury and improved survival.",2016 Aug 9,"['Meliopoulos, Victoria A.', 'Van de Velde, Lee-Ann', 'Van de Velde, Nicholas C.', 'Karlsson, Erik A.', 'Neale, Geoff', 'Vogel, Peter', 'Guy, Cliff', 'Sharma, Shalini', 'Duan, Susu', 'Surman, Sherri L.', 'Jones, Bart G.', 'Johnson, Michael D. L.', 'Bosio, Catharine', 'Jolly, Lisa', 'Jenkins, R. Gisli', 'Hurwitz, Julia L.', 'Rosch, Jason W.', 'Sheppard, Dean', 'Thomas, Paul G.', 'Murray, Peter J.', 'Schultz-Cherry, Stacey']",PLoS Pathog,,,True
6865c538b9045fd64c560c10a4f1855300a221a3,PMC,Bat–man disease transmission: zoonotic pathogens from wildlife reservoirs to human populations,http://dx.doi.org/10.1038/cddiscovery.2016.48,PMC4979447,27551536,CC BY,"Bats are natural reservoir hosts and sources of infection of several microorganisms, many of which cause severe human diseases. Because of contact between bats and other animals, including humans, the possibility exists for additional interspecies transmissions and resulting disease outbreaks. The purpose of this article is to supply an overview on the main pathogens isolated from bats that have the potential to cause disease in humans.",2016 Jun 27,"['Allocati, N', 'Petrucci, A G', 'Di Giovanni, P', 'Masulli, M', 'Di Ilio, C', 'De Laurenzi, V']",Cell Death Discov,,,True
77907b0bbf75ae10794ca69d97b9874159db1857,PMC,Visual analytics of geo-social interaction patterns for epidemic control,http://dx.doi.org/10.1186/s12942-016-0059-3,PMC4980799,27510908,CC BY,"BACKGROUND: Human interaction and population mobility determine the spatio-temporal course of the spread of an airborne disease. This research views such spreads as geo-social interaction problems, because population mobility connects different groups of people over geographical locations via which the viruses transmit. Previous research argued that geo-social interaction patterns identified from population movement data can provide great potential in designing effective pandemic mitigation. However, little work has been done to examine the effectiveness of designing control strategies taking into account geo-social interaction patterns. METHODS: To address this gap, this research proposes a new framework for effective disease control; specifically this framework proposes that disease control strategies should start from identifying geo-social interaction patterns, designing effective control measures accordingly, and evaluating the efficacy of different control measures. This framework is used to structure design of a new visual analytic tool that consists of three components: a reorderable matrix for geo-social mixing patterns, agent-based epidemic models, and combined visualization methods. RESULTS: With real world human interaction data in a French primary school as a proof of concept, this research compares the efficacy of vaccination strategies between the spatial–social interaction patterns and the whole areas. The simulation results show that locally targeted vaccination has the potential to keep infection to a small number and prevent spread to other regions. At some small probability, the local control strategies will fail; in these cases other control strategies will be needed. This research further explores the impact of varying spatial–social scales on the success of local vaccination strategies. The results show that a proper spatial–social scale can help achieve the best control efficacy with a limited number of vaccines. CONCLUSIONS: The case study shows how GS-EpiViz does support the design and testing of advanced control scenarios in airborne disease (e.g., influenza). The geo-social patterns identified through exploring human interaction data can help target critical individuals, locations, and clusters of locations for disease control purposes. The varying spatial–social scales can help geographically and socially prioritize limited resources (e.g., vaccines).",2016 Aug 10,"Luo, Wei",Int J Health Geogr,,,True
02c9b77cb2898b1597278dbf32a0c61be93d1983,PMC,Terpene metabolic engineering via nuclear or chloroplast genomes profoundly and globally impacts off‐target pathways through metabolite signalling,http://dx.doi.org/10.1111/pbi.12548,PMC4980996,27507797,CC BY,"The impact of metabolic engineering on nontarget pathways and outcomes of metabolic engineering from different genomes are poorly understood questions. Therefore, squalene biosynthesis genes FARNESYL DIPHOSPHATE SYNTHASE (FPS) and SQUALENE SYNTHASE (SQS) were engineered via the Nicotiana tabacum chloroplast (C), nuclear (N) or both (CN) genomes to promote squalene biosynthesis. SQS levels were ~4300‐fold higher in C and CN lines than in N, but all accumulated ~150‐fold higher squalene due to substrate or storage limitations. Abnormal leaf and flower phenotypes, including lower pollen production and reduced fertility, were observed regardless of the compartment or level of transgene expression. Substantial changes in metabolomes of all lines were observed: levels of 65–120 unrelated metabolites, including the toxic alkaloid nicotine, changed by as much as 32‐fold. Profound effects of transgenesis on nontarget gene expression included changes in the abundance of 19 076 transcripts by up to 2000‐fold in CN; 7784 transcripts by up to 1400‐fold in N; and 5224 transcripts by as much as 2200‐fold in C. Transporter‐related transcripts were induced, and cell cycle‐associated transcripts were disproportionally repressed in all three lines. Transcriptome changes were validated by qRT‐PCR. The mechanism underlying these large changes likely involves metabolite‐mediated anterograde and/or retrograde signalling irrespective of the level of transgene expression or end product, due to imbalance of metabolic pools, offering new insight into both anticipated and unanticipated consequences of metabolic engineering.",2016 Sep 8,"['Pasoreck, Elise K.', 'Su, Jin', 'Silverman, Ian M.', 'Gosai, Sager J.', 'Gregory, Brian D.', 'Yuan, Joshua S.', 'Daniell, Henry']",Plant Biotechnol J,,,True
327803ba593def74cf64634bc148a46935a3dd10,PMC,"Influenza-like illness outbreaks in nursing homes in Corsica, France, 2014–2015: epidemiological and molecular characterization",http://dx.doi.org/10.1186/s40064-016-2957-z,PMC4981007,27563533,CC BY,"BACKGROUND: To study the molecular epidemiology of the influenza outbreaks in nursing homes (NHs) to determine whether multiple influenza strains were involved. METHODS: From September to December 2014, NHs in Corsica were invited to participate in an ongoing daily epidemiological and microbiological surveillance for influenza-like illness (ILI) among residents and health care workers (HCWs). RESULTS: The study involved 12 NHs. Respiratory illness meeting the ILI case definition was observed among 44 residents from whom 22 specimens were collected. Of the 22 residents with a nasopharyngeal sample, 13 (59 %) were positive for at least one of the 11 pathogens analysed. Among these 13 patients, 11 (92 %) presented a confirmed influenza (A/H3N2) and two had another respiratory virus: one human metapneumovirus and one human coronavirus. Of patients with a confirmed influenza A(H3N2), 10 (91 %) were vaccinated against influenza during the 2014–2015 season. Two influenza outbreaks were reported in two NHs, caused by influenza A(H3N2) strains belonging to cluster 3C.3 and 3C.2a. Although antivirals were available, prophylaxis was not used. CONCLUSIONS: Phylogenetic analysis seems to suggest no multiple introduction into the two NHs reporting the two influenza A(H3N2) outbreaks. A number of factors could have contributed to transmitting influenza in NHs including, the absence of administration of antiviral treatment for prophylaxis of all residents/staff regardless of immunization status because of the poor vaccine match during each outbreak, the intensive contacts with incompletely protected residents and HCWs, and the low adherence of NHs to notification of ILI outbreaks to the health authorities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-016-2957-z) contains supplementary material, which is available to authorized users.",2016 Aug 11,"['Masse, S.', 'Minodier, L.', 'Heuze, G.', 'Blanchon, T.', 'Capai, L.', 'Falchi, A.']",Springerplus,,,True
db3824a1c673ce4d1bb41c065065598089c89578,PMC,Common Genetic Polymorphisms within NFκB-Related Genes and the Risk of Developing Invasive Aspergillosis,http://dx.doi.org/10.3389/fmicb.2016.01243,PMC4982195,27570521,CC BY,"Invasive Aspergillosis (IA) is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mold. A growing number of studies suggest a major host genetic component in disease susceptibility. Here, we evaluated whether 14 single-nucleotide polymorphisms within NFκB1, NFκB2, RelA, RelB, Rel, and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non-IA) recruited through a collaborative effort involving the aspBIOmics consortium and four European clinical institutions. No significant overall associations between selected SNPs and the risk of IA were found in this large cohort. Although a hematopoietic stem cell transplantation (HSCT)-stratified analysis revealed that carriers of the IRF4(rs12203592T/T) genotype had a six-fold increased risk of developing the infection when compared with those carrying the C allele (OR(REC) = 6.24, 95%CI 1.25–31.2, P = 0.026), the association of this variant with IA risk did not reach significance at experiment-wide significant threshold. In addition, we found an association of the IRF4(AATC) and IRF4(GGTC) haplotypes (not including the IRF4(rs12203592T) risk allele) with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4(rs12203592) SNP. Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found. These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA.",2016 Aug 12,"['Lupiañez, Carmen B.', 'Villaescusa, María T.', 'Carvalho, Agostinho', 'Springer, Jan', 'Lackner, Michaela', 'Sánchez-Maldonado, José M.', 'Canet, Luz M.', 'Cunha, Cristina', 'Segura-Catena, Juana', 'Alcazar-Fuoli, Laura', 'Solano, Carlos', 'Fianchi, Luana', 'Pagano, Livio', 'Potenza, Leonardo', 'Aguado, José M.', 'Luppi, Mario', 'Cuenca-Estrella, Manuel', 'Lass-Flörl, Cornelia', 'Einsele, Hermann', 'Vázquez, Lourdes', None, 'Ríos-Tamayo, Rafael', 'Loeffler, Jurgen', 'Jurado, Manuel', 'Sainz, Juan']",Front Microbiol,,,True
1ccc635c4d6c62091bbf7df3f8e4f36803ea1a32,PMC,First identification of mammalian orthoreovirus type 3 in diarrheic pigs in Europe,http://dx.doi.org/10.1186/s12985-016-0593-4,PMC4983005,27519739,CC BY,Mammalian Orthoreoviruses 3 (MRV3) have been described in diarrheic pigs from USA and Asia. We firstly detected MRV3 in Europe (Italy) in piglets showing severe diarrhea associated with Porcine Epidemic Diarrhea. The virus was phylogenetically related to European reoviruses of human and bat origin and to US and Chinese pig MRV3.,2016 Aug 12,"['Lelli, Davide', 'Beato, Maria Serena', 'Cavicchio, Lara', 'Lavazza, Antonio', 'Chiapponi, Chiara', 'Leopardi, Stefania', 'Baioni, Laura', 'De Benedictis, Paola', 'Moreno, Ana']",Virol J,,,True
1d32215c90a79509e66eb1f6e3e05b077d08ee1b,PMC,Assembly of Replication-Incompetent African Horse Sickness Virus Particles: Rational Design of Vaccines for All Serotypes,http://dx.doi.org/10.1128/JVI.00548-16,PMC4984648,27279609,CC BY,"African horse sickness virus (AHSV), an orbivirus in the Reoviridae family with nine different serotypes, causes devastating disease in equids. The virion particle is composed of seven proteins organized in three concentric layers, an outer layer made of VP2 and VP5, a middle layer made of VP7, and inner layer made of VP3 that encloses a replicase complex of VP1, VP4, and VP6 and a genome of 10 double-stranded RNA segments. In this study, we sought to develop highly efficacious candidate vaccines against all AHSV serotypes, taking into account not only immunogenic and safety properties but also virus productivity and stability parameters, which are essential criteria for vaccine candidates. To achieve this goal, we first established a highly efficient reverse genetics (RG) system for AHSV serotype 1 (AHSV1) and, subsequently, a VP6-defective AHSV1 strain in combination with in trans complementation of VP6. This was then used to generate defective particles of all nine serotypes, which required the exchange of two to five RNA segments to achieve equivalent titers of particles. All reassortant-defective viruses could be amplified and propagated to high titers in cells complemented with VP6 but were totally incompetent in any other cells. Furthermore, these replication-incompetent AHSV particles were demonstrated to be highly protective against homologous virulent virus challenges in type I interferon receptor (IFNAR)-knockout mice. Thus, these defective viruses have the potential to be used for the development of safe and stable vaccine candidates. The RG system also provides a powerful tool for the study of the role of individual AHSV proteins in virus assembly, morphogenesis, and pathogenesis. IMPORTANCE African horse sickness virus is transmitted by biting midges and causes African horse sickness in equids, with mortality reaching up to 95% in naive horses. Therefore, the development of efficient vaccines is extremely important due to major economic losses in the equine industry. Through the establishment of a highly efficient RG system, replication-deficient viruses of all nine AHSV serotypes were generated. These defective viruses achieved high titers in a cell line complemented with VP6 but failed to propagate in wild-type mammalian or insect cells. Importantly, these candidate vaccine strains showed strong protective efficacy against AHSV infection in an IFNAR(−/−) mouse model.",2016 Jul 27,"['Lulla, Valeria', 'Lulla, Aleksei', 'Wernike, Kerstin', 'Aebischer, Andrea', 'Beer, Martin', 'Roy, Polly']",J Virol,,,True
d26fb6227fcc98e9e8f9fecbedfd47bc4c00e7ba,PMC,Self-Amplifying mRNA Vaccines Expressing Multiple Conserved Influenza Antigens Confer Protection against Homologous and Heterosubtypic Viral Challenge,http://dx.doi.org/10.1371/journal.pone.0161193,PMC4985159,27525409,CC BY,"Current hemagglutinin (HA)-based seasonal influenza vaccines induce vaccine strain-specific neutralizing antibodies that usually fail to provide protection against mismatched circulating viruses. Inclusion in the vaccine of highly conserved internal proteins such as the nucleoprotein (NP) and the matrix protein 1 (M1) was shown previously to increase vaccine efficacy by eliciting cross-reactive T-cells. However, appropriate delivery systems are required for efficient priming of T-cell responses. In this study, we demonstrated that administration of novel self-amplifying mRNA (SAM(®)) vectors expressing influenza NP (SAM(NP)), M1 (SAM(M1)), and NP and M1 (SAM(M1-NP)) delivered with lipid nanoparticles (LNP) induced robust polyfunctional CD4 T helper 1 cells, while NP-containing SAM also induced cytotoxic CD8 T cells. Robust expansions of central memory (T(CM)) and effector memory (T(EM)) CD4 and CD8 T cells were also measured. An enhanced recruitment of NP-specific cytotoxic CD8 T cells was observed in the lungs of SAM(NP)-immunized mice after influenza infection that paralleled with reduced lung viral titers and pathology, and increased survival after homologous and heterosubtypic influenza challenge. Finally, we demonstrated for the first time that the co-administration of RNA (SAM(M1-NP)) and protein (monovalent inactivated influenza vaccine (MIIV)) was feasible, induced simultaneously NP-, M1- and HA-specific T cells and HA-specific neutralizing antibodies, and enhanced MIIV efficacy against a heterologous challenge. In conclusion, systemic administration of SAM vectors expressing conserved internal influenza antigens induced protective immune responses in mice, supporting the SAM(®) platform as another promising strategy for the development of broad-spectrum universal influenza vaccines.",2016 Aug 15,"['Magini, Diletta', 'Giovani, Cinzia', 'Mangiavacchi, Simona', 'Maccari, Silvia', 'Cecchi, Raffaella', 'Ulmer, Jeffrey B.', 'De Gregorio, Ennio', 'Geall, Andrew J.', 'Brazzoli, Michela', 'Bertholet, Sylvie']",PLoS One,,,True
1faad9ed0f7640ab69cac98df7db103f99e66066,PMC,Adaptation in protein fitness landscapes is facilitated by indirect paths,http://dx.doi.org/10.7554/eLife.16965,PMC4985287,27391790,CC BY,"The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two amino acids at each site. In reality, the dimensionality of protein sequence space is higher (20(L)) and there may be higher-order interactions among more than two sites. Here we experimentally characterized the fitness landscape of four sites in protein GB1, containing 20(4) = 160,000 variants. We found that while reciprocal sign epistasis blocked many direct paths of adaptation, such evolutionary traps could be circumvented by indirect paths through genotype space involving gain and subsequent loss of mutations. These indirect paths alleviate the constraint on adaptive protein evolution, suggesting that the heretofore neglected dimensions of sequence space may change our views on how proteins evolve. DOI: http://dx.doi.org/10.7554/eLife.16965.001",,"['Wu, Nicholas C', 'Dai, Lei', 'Olson, C Anders', 'Lloyd-Smith, James O', 'Sun, Ren']",eLife.; 5:e16965,,,True
9b5d40c82f807736a65c47b53824f36e220ef9d0,PMC,"Incidence and Outcomes of Acute Respiratory Distress Syndrome: A Nationwide Registry-Based Study in Taiwan, 1997 to 2011",http://dx.doi.org/10.1097/MD.0000000000001849,PMC4985407,26512593,CC BY,"Most epidemiological studies of acute respiratory distress syndrome (ARDS) have been conducted in western countries, and studies in Asia are limited. The aim of our study was to evaluate the incidence, in-hospital mortality, and 1-year mortality of ARDS in Taiwan. We conducted a nationwide inpatient cohort study based on the Taiwan National Health Insurance Research Database between 1997 and 2011. A total of 40,876 ARDS patients (68% male; mean age 66 years) were identified by International Classification of Diseases, 9th edition coding and further analyzed for clinical characteristics, medical costs, and mortality. The overall crude incidence of ARDS was 15.74 per 100,000 person-years, and increased from 2.53 to 19.26 per 100,000 person-years during the study period. The age-adjusted incidence of ARDS was 15.19 per 100,000 person-years. The overall in-hospital mortality was 57.8%. In-hospital mortality decreased from 59.7% in 1997 to 47.5% in 2011 (P < 0.001). The in-hospital mortality rate was lowest (33.5%) in the youngest patients (age 18–29 years) and highest (68.2%) in the oldest patients (>80 years, P < 0.001). The overall 1-year mortality rate was 72.1%, and decreased from 75.8% to 54.7% during the study period. Patients who died during hospitalization were older (69 ± 17 versus 62 ± 19, P < 0.001) and predominantly male (69.8% versus 65.3%, P < 0.001). In addition, patients who died during hospitalization had significantly higher medical costs (6421 versus 5825 US Dollars, P < 0.001) and shorter lengths of stay (13 versus 19 days, P < 0.001) than patients who survived. We provide the first large-scale epidemiological analysis of ARDS incidence and outcomes in Asia. Although the overall incidence was lower than has been reported in a prospective US study, this may reflect underdiagnosis by International Classification of Diseases, 9th edition code and identification of only patients with more severe ARDS in this analysis. Overall, there has been a decreasing trend in in-hospital and 1-year mortality rates in recent years, likely because of the implementation of lung-protective ventilation.",2015 Oct 30,"['Chen, Wei', 'Chen, Yih-Yuan', 'Tsai, Ching-Fang', 'Chen, Solomon Chih-Cheng', 'Lin, Ming-Shian', 'Ware, Lorraine B.', 'Chen, Chuan-Mu']",Medicine (Baltimore),,,True
8133996ea269ebe90ba8c1715cf462607997d975,PMC,Insights into the transmission of respiratory infectious diseases through empirical human contact networks,http://dx.doi.org/10.1038/srep31484,PMC4985757,27526868,CC BY,"In this study, we present representative human contact networks among Chinese college students. Unlike schools in the US, human contacts within Chinese colleges are extremely clustered, partly due to the highly organized lifestyle of Chinese college students. Simulations of influenza spreading across real contact networks are in good accordance with real influenza records; however, epidemic simulations across idealized scale-free or small-world networks show considerable overestimation of disease prevalence, thus challenging the widely-applied idealized human contact models in epidemiology. Furthermore, the special contact pattern within Chinese colleges results in disease spreading patterns distinct from those of the US schools. Remarkably, class cancelation, though simple, shows a mitigating power equal to quarantine/vaccination applied on ~25% of college students, which quantitatively explains its success in Chinese colleges during the SARS period. Our findings greatly facilitate reliable prediction of epidemic prevalence, and thus should help establishing effective strategies for respiratory infectious diseases control.",2016 Aug 16,"['Huang, Chunlin', 'Liu, Xingwu', 'Sun, Shiwei', 'Li, Shuai Cheng', 'Deng, Minghua', 'He, Guangxue', 'Zhang, Haicang', 'Wang, Chao', 'Zhou, Yang', 'Zhao, Yanlin', 'Bu, Dongbo']",Sci Rep,,,True
25c68946a75609c08c00a639ba839a67316cd034,PMC,Insights into the transmission of respiratory infectious diseases through empirical human contact networks,http://dx.doi.org/10.1038/srep31484,PMC4985757,27526868,CC BY,"In this study, we present representative human contact networks among Chinese college students. Unlike schools in the US, human contacts within Chinese colleges are extremely clustered, partly due to the highly organized lifestyle of Chinese college students. Simulations of influenza spreading across real contact networks are in good accordance with real influenza records; however, epidemic simulations across idealized scale-free or small-world networks show considerable overestimation of disease prevalence, thus challenging the widely-applied idealized human contact models in epidemiology. Furthermore, the special contact pattern within Chinese colleges results in disease spreading patterns distinct from those of the US schools. Remarkably, class cancelation, though simple, shows a mitigating power equal to quarantine/vaccination applied on ~25% of college students, which quantitatively explains its success in Chinese colleges during the SARS period. Our findings greatly facilitate reliable prediction of epidemic prevalence, and thus should help establishing effective strategies for respiratory infectious diseases control.",2016 Aug 16,"['Huang, Chunlin', 'Liu, Xingwu', 'Sun, Shiwei', 'Li, Shuai Cheng', 'Deng, Minghua', 'He, Guangxue', 'Zhang, Haicang', 'Wang, Chao', 'Zhou, Yang', 'Zhao, Yanlin', 'Bu, Dongbo']",Sci Rep,,,True
ab85c4fceac01205bc463599fa6263a6498528c1,PMC,Pertussis in infants: an underestimated disease,http://dx.doi.org/10.1186/s12879-016-1710-0,PMC4986228,27528377,CC BY,"BACKGROUND: The clinical diagnosis of pertussis is not easy in early infancy since clinical manifestations can overlap with several different diseases. Many cases are often misclassified and underdiagnosed. We conducted a retrospective study on infants to assess how often physicians suspected pertussis and the actual frequency of Bordetella pertussis infections. METHODS: We analyzed all infants with age ≤90 days hospitalized from March 2011 until September 2013 for acute respiratory symptoms tested with a Real Time Polymerase Chain Reaction able to detect Bordetella pertussis and with a Real Time Polymerase Chain Reaction for a multipanel respiratory virus. Therefore, we compared patients with pertussis positive aspirate, patients with respiratory virus positive aspirate and patients with negative aspirate to identify symptoms or clinical findings predictive of pertussis. RESULTS: Out of 215 patients analyzed, 53 were positive for pertussis (24.7 %), 119 were positive for respiratory virus (55.3 %) and 43 had a negative aspirate (20 %). Pertussis was suspected in 22 patients at admission and 16 of them were confirmed by laboratory tests, while 37 infants with different admission diagnosis resulted positive for pertussis. The sensitivity of clinical diagnosis was 30.2 % and the specificity 96.3 %. Infants with pertussis had more often paroxysmal cough, absence of fever and a higher absolute lymphocyte count than infants without pertussis. CONCLUSIONS: Pertussis is a serious disease in infants and it is often unrecognized; some features should help pediatricians to suspect pertussis, but clinical suspicion has a low sensitivity. We suggest a systematic use of Real Time Polymerase Chain Reaction to support the clinical suspicion of pertussis in patients with less than 3 months of age hospitalized with acute respiratory symptoms.",2016 Aug 15,"['Vittucci, Anna Chiara', 'Spuri Vennarucci, Valentina', 'Grandin, Annalisa', 'Russo, Cristina', 'Lancella, Laura', 'Tozzi, Albero Eugenio', 'Bartuli, Andrea', 'Villani, Alberto']",BMC Infect Dis,,,True
2fac2663c1643fe03479ddfc4122ec63bf269803,PMC,Linear Quantitative Profiling Method Fast Monitors Alkaloids of Sophora Flavescens That Was Verified by Tri-Marker Analyses,http://dx.doi.org/10.1371/journal.pone.0161146,PMC4987015,27529425,CC BY,"The present study demonstrated the use of the Linear Quantitative Profiling Method (LQPM) to evaluate the quality of Alkaloids of Sophora flavescens (ASF) based on chromatographic fingerprints in an accurate, economical and fast way. Both linear qualitative and quantitative similarities were calculated in order to monitor the consistency of the samples. The results indicate that the linear qualitative similarity (LQLS) is not sufficiently discriminating due to the predominant presence of three alkaloid compounds (matrine, sophoridine and oxymatrine) in the test samples; however, the linear quantitative similarity (LQTS) was shown to be able to obviously identify the samples based on the difference in the quantitative content of all the chemical components. In addition, the fingerprint analysis was also supported by the quantitative analysis of three marker compounds. The LQTS was found to be highly correlated to the contents of the marker compounds, indicating that quantitative analysis of the marker compounds may be substituted with the LQPM based on the chromatographic fingerprints for the purpose of quantifying all chemicals of a complex sample system. Furthermore, once reference fingerprint (RFP) developed from a standard preparation in an immediate detection way and the composition similarities calculated out, LQPM could employ the classical mathematical model to effectively quantify the multiple components of ASF samples without any chemical standard.",2016 Aug 16,"['Hou, Zhifei', 'Sun, Guoxiang', 'Guo, Yong']",PLoS One,,,True
f217296b50c75def2bfed98fec3db692e9339f70,PMC,Make Data Sharing Routine to Prepare for Public Health Emergencies,http://dx.doi.org/10.1371/journal.pmed.1002109,PMC4987038,27529422,CC0,Jean-Paul Chretien and colleagues argue that recent Ebola and Zika virus outbreaks highlight the importance of data sharing in scientific research.,2016 Aug 16,"['Chretien, Jean-Paul', 'Rivers, Caitlin M.', 'Johansson, Michael A.']",PLoS Med,,,True
858f420ea81730f250e270096dc9efef9831c1dd,PMC,Nearly full-length genome sequence of a novel astrovirus isolated from chickens with ‘white chicks’ condition,http://dx.doi.org/10.1007/s00705-016-2940-6,PMC4987400,27339687,CC BY,"Avian astroviruses (aAstVs) are divided into three species, Avastrovirus 1, Avastrovirus 2, and Avastrovirus 3, but there are a few strains are waiting to be assigned to an official taxonomic group. This study presents the molecular characterization of chicken astrovirus (CAstV), PL/G059/2014, which is involved in the induction of “white chicks” condition. The 7382-nucleotide-long genome sequence was determined by next-generation sequencing using an Illumina MiSeq System. Phylogenetic analysis showed that it has the characteristics that are typical of avian astroviruses. However, overall degree of nucleotide sequence identity was 43.6 % to 73.7 % between PL/G059/2014 and other available genome sequences of aAstV strains. The amino acid sequences of the proteins encoded by ORF1a and ORF1b of the studied strain were very similar (86.5-93.8 % identity) to those of CAstVs 4175 and GA2011, but they were only 32.7-35.2 % identical in the case of ORF2, which is used officially for astrovirus species demarcation. These features could suggest that the PL/G059/2014 strain should be assigned to a new species in the genus Avastrovirus. Moreover, the different phylogenetic topology of PL/G059/2014 and its nucleotide sequence similarity in different genomic regions could suggest that a recombination event occurred during its evolution and that it has ancestors in common with duck astroviruses.",2016 Jun 23,"['Sajewicz-Krukowska, Joanna', 'Domanska-Blicharz, Katarzyna']",Arch Virol,,,True
1aeb1b6c5213c80ebd33f69021776928ee1fc315,PMC,"Brief review of the chicken Major Histocompatibility Complex: the genes, their distribution on chromosome 16, and their contributions to disease resistance",http://dx.doi.org/10.3382/ps/pev379,PMC4988538,26740135,CC BY,"Nearly all genes presently mapped to chicken chromosome 16 (GGA 16) have either a demonstrated role in immune responses or are considered to serve in immunity by reason of sequence homology with immune system genes defined in other species. The genes are best described in regional units. Among these, the best known is the polymorphic major histocompatibility complex-B (MHC-B) region containing genes for classical peptide antigen presentation. Nearby MHC-B is a small region containing two CD1 genes, which encode molecules known to bind lipid antigens and which will likely be found in chickens to present lipids to specialized T cells, as occurs with CD1 molecules in other species. Another region is the MHC-Y region, separated from MHC-B by an intervening region of tandem repeats. Like MHC-B, MHC-Y is polymorphic. It contains specialized class I and class II genes and c-type lectin-like genes. Yet another region, separated from MHC-Y by the single nucleolar organizing region (NOR) in the chicken genome, contains olfactory receptor genes and scavenger receptor genes, which are also thought to contribute to immunity. The structure, distribution, linkages and patterns of polymorphism in these regions, suggest GGA 16 evolves as a microchromosome devoted to immune defense. Many GGA 16 genes are polymorphic and polygenic. At the moment most disease associations are at the haplotype level. Roles of individual MHC genes in disease resistance are documented in only a very few instances. Provided suitable experimental stocks persist, the availability of increasingly detailed maps of GGA 16 genes combined with new means for detecting genetic variability will lead to investigations defining the contributions of individual loci and more applications for immunogenetics in breeding healthy poultry.",2016 Feb 17,"['Miller, Marcia M.', 'Taylor, Robert L.']",Poult Sci,,,True
9db78243c51590cfaaef835ded1163dc55d67cc0,PMC,Sustained Viremia and High Viral Load in Respiratory Tract Secretions Are Predictors for Death in Immunocompetent Adults with Adenovirus Pneumonia,http://dx.doi.org/10.1371/journal.pone.0160777,PMC4988761,27532864,CC BY,"The predictors for fatal adenovirus (AdV) pneumonia among immunocompetent adults are unclear. Laboratory-confirmed, hospitalized AdV pneumonia adults were prospectively enrolled in Beijing Chao-Yang hospital from March to June 2013. Clinical data and serial whole blood and respiratory tract secretions from such patients were collected. Quantitative real-time polymerase chain reaction was performed to quantify the viral load. A total of 14 AdV pneumonia cases were consecutively enrolled, and four of them were fatal. Ten cases were caused by AdV-55, three by AdV-7 and one by AdV-3. There were no differences in age, gender or underlying diseases between the patients in the fatal cases and surviving cases. At admission (on day 5–7 after illness onset), the patients in fatal cases presented higher initial viral loads in respiratory tract secretions (8.578 ± 2.115 vs 6.263 ± 1.225 Log(10) copies/ml, p = 0.023). All patients in fatal cases presented with viremia on day 12–14 (100% vs 66.7%, p = 0.017). A higher initial viral load in the respiratory tract and sustained viremia (more than 2 weeks) may be predictors for fatal clinical outcomes.",2016 Aug 17,"['Gu, Li', 'Qu, Jiuxin', 'Sun, Bing', 'Yu, Xiaomin', 'Li, Hui', 'Cao, Bin']",PLoS One,,,True
81d66de97e0d60ca4e91efa3aa95f684b914a865,PMC,Mass Gatherings and Respiratory Disease Outbreaks in the United States – Should We Be Worried? Results from a Systematic Literature Review and Analysis of the National Outbreak Reporting System,http://dx.doi.org/10.1371/journal.pone.0160378,PMC4990208,27536770,CC0,"BACKGROUND: Because mass gatherings create environments conducive for infectious disease transmission, public health officials may recommend postponing or canceling large gatherings during a moderate or severe pandemic. Despite these recommendations, limited empirical information exists on the frequency and characteristics of mass gathering-related respiratory disease outbreaks occurring in the United States. METHODS: We conducted a systematic literature review to identify articles about mass gathering-related respiratory disease outbreaks occurring in the United States from 2005 to 2014. A standard form was used to abstract information from relevant articles identified from six medical, behavioral and social science literature databases. We also analyzed data from the National Outbreaks Reporting System (NORS), maintained by the Centers for Disease Control and Prevention since 2009, to estimate the frequency of mass gathering-related respiratory disease outbreaks reported to the system. RESULTS: We identified 21 published articles describing 72 mass gathering-related respiratory disease outbreaks. Of these 72, 40 (56%) were associated with agriculture fairs and Influenza A H3N2v following probable swine exposure, and 25 (35%) with youth summer camps and pandemic Influenza A H1N1. Outbreaks of measles (n = 1) and mumps (n = 2) were linked to the international importation of disease. Between 2009 and 2013, 1,114 outbreaks were reported to NORS, including 96 respiratory disease outbreaks due to Legionella. None of these legionellosis outbreaks was linked to a mass gathering according to available data. CONCLUSION: Mass gathering-related respiratory disease outbreaks may be uncommon in the United States, but have been reported from fairs (zoonotic transmission) as well as at camps where participants have close social contact in communal housing. International importation can also be a contributing factor. NORS collects information on certain respiratory diseases and could serve as a platform to monitor mass gathering-related respiratory outbreaks in the future.",2016 Aug 18,"['Rainey, Jeanette J.', 'Phelps, Tiffani', 'Shi, Jianrong']",PLoS One,,,True
83f3e687e4f87182b3c1d4749e27a559c8b5ab26,PMC,Mass Gatherings and Respiratory Disease Outbreaks in the United States – Should We Be Worried? Results from a Systematic Literature Review and Analysis of the National Outbreak Reporting System,http://dx.doi.org/10.1371/journal.pone.0160378,PMC4990208,27536770,CC0,"BACKGROUND: Because mass gatherings create environments conducive for infectious disease transmission, public health officials may recommend postponing or canceling large gatherings during a moderate or severe pandemic. Despite these recommendations, limited empirical information exists on the frequency and characteristics of mass gathering-related respiratory disease outbreaks occurring in the United States. METHODS: We conducted a systematic literature review to identify articles about mass gathering-related respiratory disease outbreaks occurring in the United States from 2005 to 2014. A standard form was used to abstract information from relevant articles identified from six medical, behavioral and social science literature databases. We also analyzed data from the National Outbreaks Reporting System (NORS), maintained by the Centers for Disease Control and Prevention since 2009, to estimate the frequency of mass gathering-related respiratory disease outbreaks reported to the system. RESULTS: We identified 21 published articles describing 72 mass gathering-related respiratory disease outbreaks. Of these 72, 40 (56%) were associated with agriculture fairs and Influenza A H3N2v following probable swine exposure, and 25 (35%) with youth summer camps and pandemic Influenza A H1N1. Outbreaks of measles (n = 1) and mumps (n = 2) were linked to the international importation of disease. Between 2009 and 2013, 1,114 outbreaks were reported to NORS, including 96 respiratory disease outbreaks due to Legionella. None of these legionellosis outbreaks was linked to a mass gathering according to available data. CONCLUSION: Mass gathering-related respiratory disease outbreaks may be uncommon in the United States, but have been reported from fairs (zoonotic transmission) as well as at camps where participants have close social contact in communal housing. International importation can also be a contributing factor. NORS collects information on certain respiratory diseases and could serve as a platform to monitor mass gathering-related respiratory outbreaks in the future.",2016 Aug 18,"['Rainey, Jeanette J.', 'Phelps, Tiffani', 'Shi, Jianrong']",PLoS One,,,False
b8797e77d9c91dd2cab19ba2e67cf32b6dd97bf6,PMC,Mass Gatherings and Respiratory Disease Outbreaks in the United States – Should We Be Worried? Results from a Systematic Literature Review and Analysis of the National Outbreak Reporting System,http://dx.doi.org/10.1371/journal.pone.0160378,PMC4990208,27536770,CC0,"BACKGROUND: Because mass gatherings create environments conducive for infectious disease transmission, public health officials may recommend postponing or canceling large gatherings during a moderate or severe pandemic. Despite these recommendations, limited empirical information exists on the frequency and characteristics of mass gathering-related respiratory disease outbreaks occurring in the United States. METHODS: We conducted a systematic literature review to identify articles about mass gathering-related respiratory disease outbreaks occurring in the United States from 2005 to 2014. A standard form was used to abstract information from relevant articles identified from six medical, behavioral and social science literature databases. We also analyzed data from the National Outbreaks Reporting System (NORS), maintained by the Centers for Disease Control and Prevention since 2009, to estimate the frequency of mass gathering-related respiratory disease outbreaks reported to the system. RESULTS: We identified 21 published articles describing 72 mass gathering-related respiratory disease outbreaks. Of these 72, 40 (56%) were associated with agriculture fairs and Influenza A H3N2v following probable swine exposure, and 25 (35%) with youth summer camps and pandemic Influenza A H1N1. Outbreaks of measles (n = 1) and mumps (n = 2) were linked to the international importation of disease. Between 2009 and 2013, 1,114 outbreaks were reported to NORS, including 96 respiratory disease outbreaks due to Legionella. None of these legionellosis outbreaks was linked to a mass gathering according to available data. CONCLUSION: Mass gathering-related respiratory disease outbreaks may be uncommon in the United States, but have been reported from fairs (zoonotic transmission) as well as at camps where participants have close social contact in communal housing. International importation can also be a contributing factor. NORS collects information on certain respiratory diseases and could serve as a platform to monitor mass gathering-related respiratory outbreaks in the future.",2016 Aug 18,"['Rainey, Jeanette J.', 'Phelps, Tiffani', 'Shi, Jianrong']",PLoS One,,,True
371c9fd77329f6bd62e32c702dfbed1bb5ae2401,PMC,Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1038/srep31629,PMC4990914,27538452,CC BY,"Middle East Respiratory Syndrome coronavirus (MERS-CoV) has repeatedly caused outbreaks in the Arabian Peninsula. To date, no approved medical countermeasures (MCM) are available to combat MERS-CoV infections. Several neutralizing human monoclonal antibodies (mAbs), including m336, a germline-like human mAb, have been chosen as promising MCM for MERS-CoV. However, their clinical development has been hindered by the lack of a robust animal model that recapitulate the morbidity and mortality of human infections. We assessed the prophylactic and therapeutic efficacy of m336 by using well-characterized transgenic mice shown to be highly sensitive to MERS-CoV infection and disease. We found that mice treated with m336 prior to or post lethal MERS-CoV challenging were fully protected, compared to control mice which sufferered from profound weight loss and uniform death within days after infection. Taken together, these results support further development of m336 and other human monoclonal antibodies as potential therapeutics for MERS-CoV infection.",2016 Aug 19,"['Agrawal, Anurodh Shankar', 'Ying, Tianlei', 'Tao, Xinrong', 'Garron, Tania', 'Algaissi, Abdullah', 'Wang, Yanping', 'Wang, Lili', 'Peng, Bi-Hung', 'Jiang, Shibo', 'Dimitrov, Dimiter S.', 'Tseng, Chien-Te K.']",Sci Rep,,,True
1b8770691fe974dfb269a16db59750370b9c0c21,PMC,Epidemiology and etiology of influenza-like-illness in households in Vietnam; it’s not all about the kids!,http://dx.doi.org/10.1016/j.jcv.2016.07.014,PMC4994428,27479176,CC BY,"BACKGROUND: Household studies provide opportunities to understand influenza-like-illness (ILI) transmission, but data from (sub)tropical developing countries are scarce. OBJECTIVE: To determine the viral etiology and epidemiology of ILI in households. STUDY DESIGN: ILI was detected by active case finding amongst a cohort of 263 northern Vietnam households between 2008 and 2013. Health workers collected nose and throat swabs for virus detection by multiplex real-time RT-PCR. RESULTS: ILI was detected at least once in 219 (23.7%) of 945 household members. 271 (62.3%) of 435 nose/throat swabs were positive for at least one of the 15 viruses tested. Six viruses predominated amongst positive swabs: Rhinovirus (28%), Influenza virus (17%), Coronavirus (8%), Enterovirus (5%), Respiratory syncytial virus (3%), Metapneumovirus virus (2.5%) and Parainfluenza virus 3 (1.8%). There was no clear seasonality, but 78% of episodes occurred in Winter/Spring for Influenza compared to 32% for Rhinovirus. Participants, on average, suffered 0.49 ILI, and 0.29 virus-positive ILI episodes, with no significant effects of gender, age, or household size. In contrast to US and Australian community studies, the frequency of ILI decreased as the number of household members aged below 5 years increased (p = 0.006). CONCLUSION: The findings indicate the need for tailored ILI control strategies, and for better understanding of how local childcare practices and seasonality may influence transmission and the role of children.",2016 Sep,"['Nguyen, Diep Ngoc Thi', 'Mai, Le Quynh', 'Bryant, Juliet E.', 'Hang, Nguyen Le Khanh', 'Hoa, Le Nguyen Minh', 'Nadjm, Behzad', 'Thai, Pham Quang', 'Duong, Tran Nhu', 'Anh, Dang Duc', 'Horby, Peter', 'van Doorn, H. Rogier', 'Wertheim, Heiman F.L.', 'Fox, Annette']",J Clin Virol,,,False
b285ac5faca47fd0d835d385a193bb169447015f,PMC,TGEV infection up-regulates FcRn expression via activation of NF-κB signaling,http://dx.doi.org/10.1038/srep32154,PMC4995372,27555521,CC BY,"It has been well characterized that the neonatal Fc receptor (FcRn) transports maternal IgG to a fetus or newborn and protects IgG from degradation. We previously reported that FcRn is expressed in a model of normal porcine intestinal epithelial cells (IPEC-J2). Transmissible gastroenteritis is an acute enteric disease of swine that is caused by transmissible gastroenteritis virus (TGEV). How porcine FcRn (pFcRn) expression is regulated by pathogenic infection remains unknown. Our research shows that IPEC-J2 cells infected with TGEV had up-regulated pFcRn expression. In addition, the NF-κB signaling pathway was activated in IPEC-J2 cells by TGEV infection. Furthermore, treatment of TGEV-infected IPEC-J2 cells with the NF-κB-specific inhibitor BAY 11-7082 resulted in down-regulation of pFcRn expression. Transient transfection of pFcRn promoter luciferase report plasmids with overexpression of NF-κB p65 transcription factor enhanced the activation of the luciferase report plasmids. We identified four NF-κB transcription factor binding sites in the promoter region of this gene using luciferase reporter system, chromatin immunoprecipitation, electromobility shift assay, and supershift analysis. Together, the data provide the first evidence that TGEV infection up-regulates pFcRn expression via activation of NF-κB signaling.",2016 Aug 24,"['Guo, Jinyue', 'Li, Fei', 'Qian, Shaoju', 'Bi, Dingren', 'He, Qigai', 'Jin, Hui', 'Luo, Rui', 'Li, Shaowen', 'Meng, Xianrong', 'Li, Zili']",Sci Rep,,,True
73d0e03660b35119807acf6aafc33dc2276f19a2,PMC,TGEV infection up-regulates FcRn expression via activation of NF-κB signaling,http://dx.doi.org/10.1038/srep32154,PMC4995372,27555521,CC BY,"It has been well characterized that the neonatal Fc receptor (FcRn) transports maternal IgG to a fetus or newborn and protects IgG from degradation. We previously reported that FcRn is expressed in a model of normal porcine intestinal epithelial cells (IPEC-J2). Transmissible gastroenteritis is an acute enteric disease of swine that is caused by transmissible gastroenteritis virus (TGEV). How porcine FcRn (pFcRn) expression is regulated by pathogenic infection remains unknown. Our research shows that IPEC-J2 cells infected with TGEV had up-regulated pFcRn expression. In addition, the NF-κB signaling pathway was activated in IPEC-J2 cells by TGEV infection. Furthermore, treatment of TGEV-infected IPEC-J2 cells with the NF-κB-specific inhibitor BAY 11-7082 resulted in down-regulation of pFcRn expression. Transient transfection of pFcRn promoter luciferase report plasmids with overexpression of NF-κB p65 transcription factor enhanced the activation of the luciferase report plasmids. We identified four NF-κB transcription factor binding sites in the promoter region of this gene using luciferase reporter system, chromatin immunoprecipitation, electromobility shift assay, and supershift analysis. Together, the data provide the first evidence that TGEV infection up-regulates pFcRn expression via activation of NF-κB signaling.",2016 Aug 24,"['Guo, Jinyue', 'Li, Fei', 'Qian, Shaoju', 'Bi, Dingren', 'He, Qigai', 'Jin, Hui', 'Luo, Rui', 'Li, Shaowen', 'Meng, Xianrong', 'Li, Zili']",Sci Rep,,,False
7a32e94a4c479957e6c98108ac3eaa344bc07f7d,PMC,The rise and fall of infectious disease in a warmer world,http://dx.doi.org/10.12688/f1000research.8766.1,PMC4995683,27610227,CC BY,"Now-outdated estimates proposed that climate change should have increased the number of people at risk of malaria, yet malaria and several other infectious diseases have declined. Although some diseases have increased as the climate has warmed, evidence for widespread climate-driven disease expansion has not materialized, despite increased research attention. Biological responses to warming depend on the non-linear relationships between physiological performance and temperature, called the thermal response curve. This leads performance to rise and fall with temperature. Under climate change, host species and their associated parasites face extinction if they cannot either thermoregulate or adapt by shifting phenology or geographic range. Climate change might also affect disease transmission through increases or decreases in host susceptibility and infective stage (and vector) production, longevity, and pathology. Many other factors drive disease transmission, especially economics, and some change in time along with temperature, making it hard to distinguish whether temperature drives disease or just correlates with disease drivers. Although it is difficult to predict how climate change will affect infectious disease, an ecological approach can help meet the challenge.",2016 Aug 19,"['Lafferty, Kevin D.', 'Mordecai, Erin A.']",F1000Res,,,True
2e26e0f3a9c4729b7f8aedcd9a95b00257378e20,PMC,A Subset of Protective γ(9)δ(2) T Cells Is Activated by Novel Mycobacterial Glycolipid Components,http://dx.doi.org/10.1128/IAI.01322-15,PMC4995917,27297390,CC BY,"γ(9)δ(2) T cells provide a natural bridge between innate and adaptive immunity, rapidly and potently respond to pathogen infection in mucosal tissues, and are prominently induced by both tuberculosis (TB) infection and bacillus Calmette Guérin (BCG) vaccination. Mycobacterium-expanded γ(9)δ(2) T cells represent only a subset of the phosphoantigen {isopentenyl pyrophosphate [IPP] and (E)-4-hydroxy-3-methyl-but-2-enylpyrophosphate [HMBPP]}-responsive γ(9)δ(2) T cells, expressing an oligoclonal set of T cell receptor (TCR) sequences which more efficiently recognize and inhibit intracellular Mycobacterium tuberculosis infection. Based on this premise, we have been searching for M. tuberculosis antigens specifically capable of inducing a unique subset of mycobacterium-protective γ(9)δ(2) T cells. Our screening strategy includes the identification of M. tuberculosis fractions that expand γ(9)δ(2) T cells with biological functions capable of inhibiting intracellular mycobacterial replication. Chemical treatments of M. tuberculosis whole-cell lysates (MtbWL) ruled out protein, nucleic acid, and nonpolar lipids as the M. tuberculosis antigens inducing protective γ(9)δ(2) T cells. Mild acid hydrolysis, which transforms complex carbohydrate to monomeric residues, abrogated the specific activity of M. tuberculosis whole-cell lysates, suggesting that a polysaccharide was required for biological activity. Extraction of MtbWL with chloroform-methanol-water (10:10:3) resulted in a polar lipid fraction with highly enriched specific activity; this activity was further enriched by silica gel chromatography. A combination of mass spectrometry and nuclear magnetic resonance analysis of bioactive fractions indicated that 6-O-methylglucose-containing lipopolysaccharides (mGLP) are predominant components present in this active fraction. These results have important implications for the development of new immunotherapeutic approaches for prevention and treatment of TB.",2016 Aug 19,"['Xia, Mei', 'Hesser, Danny C.', 'De, Prithwiraj', 'Sakala, Isaac G.', 'Spencer, Charles T.', 'Kirkwood, Jay S.', 'Abate, Getahun', 'Chatterjee, Delphi', 'Dobos, Karen M.', 'Hoft, Daniel F.']",Infect Immun,,,False
f030f518075c344748867210874ab67ffd02259e,PMC,A Subset of Protective γ(9)δ(2) T Cells Is Activated by Novel Mycobacterial Glycolipid Components,http://dx.doi.org/10.1128/IAI.01322-15,PMC4995917,27297390,CC BY,"γ(9)δ(2) T cells provide a natural bridge between innate and adaptive immunity, rapidly and potently respond to pathogen infection in mucosal tissues, and are prominently induced by both tuberculosis (TB) infection and bacillus Calmette Guérin (BCG) vaccination. Mycobacterium-expanded γ(9)δ(2) T cells represent only a subset of the phosphoantigen {isopentenyl pyrophosphate [IPP] and (E)-4-hydroxy-3-methyl-but-2-enylpyrophosphate [HMBPP]}-responsive γ(9)δ(2) T cells, expressing an oligoclonal set of T cell receptor (TCR) sequences which more efficiently recognize and inhibit intracellular Mycobacterium tuberculosis infection. Based on this premise, we have been searching for M. tuberculosis antigens specifically capable of inducing a unique subset of mycobacterium-protective γ(9)δ(2) T cells. Our screening strategy includes the identification of M. tuberculosis fractions that expand γ(9)δ(2) T cells with biological functions capable of inhibiting intracellular mycobacterial replication. Chemical treatments of M. tuberculosis whole-cell lysates (MtbWL) ruled out protein, nucleic acid, and nonpolar lipids as the M. tuberculosis antigens inducing protective γ(9)δ(2) T cells. Mild acid hydrolysis, which transforms complex carbohydrate to monomeric residues, abrogated the specific activity of M. tuberculosis whole-cell lysates, suggesting that a polysaccharide was required for biological activity. Extraction of MtbWL with chloroform-methanol-water (10:10:3) resulted in a polar lipid fraction with highly enriched specific activity; this activity was further enriched by silica gel chromatography. A combination of mass spectrometry and nuclear magnetic resonance analysis of bioactive fractions indicated that 6-O-methylglucose-containing lipopolysaccharides (mGLP) are predominant components present in this active fraction. These results have important implications for the development of new immunotherapeutic approaches for prevention and treatment of TB.",2016 Aug 19,"['Xia, Mei', 'Hesser, Danny C.', 'De, Prithwiraj', 'Sakala, Isaac G.', 'Spencer, Charles T.', 'Kirkwood, Jay S.', 'Abate, Getahun', 'Chatterjee, Delphi', 'Dobos, Karen M.', 'Hoft, Daniel F.']",Infect Immun,,,True
48bd5f768f3464ac253a120d2eddeb89c323f324,PMC,"Integrated Microfluidic Nucleic Acid Isolation, Isothermal Amplification, and Amplicon Quantification",http://dx.doi.org/10.3390/microarrays4040474,PMC4996405,27600235,CC BY,"Microfluidic components and systems for rapid (<60 min), low-cost, convenient, field-deployable sequence-specific nucleic acid-based amplification tests (NAATs) are described. A microfluidic point-of-care (POC) diagnostics test to quantify HIV viral load from blood samples serves as a representative and instructive example to discuss the technical issues and capabilities of “lab on a chip” NAAT devices. A portable, miniaturized POC NAAT with performance comparable to conventional PCR (polymerase-chain reaction)-based tests in clinical laboratories can be realized with a disposable, palm-sized, plastic microfluidic chip in which: (1) nucleic acids (NAs) are extracted from relatively large (~mL) volume sample lysates using an embedded porous silica glass fiber or cellulose binding phase (“membrane”) to capture sample NAs in a flow-through, filtration mode; (2) NAs captured on the membrane are isothermally (~65 °C) amplified; (3) amplicon production is monitored by real-time fluorescence detection, such as with a smartphone CCD camera serving as a low-cost detector; and (4) paraffin-encapsulated, lyophilized reagents for temperature-activated release are pre-stored in the chip. Limits of Detection (LOD) better than 10(3) virons/sample can be achieved. A modified chip with conduits hosting a diffusion-mode amplification process provides a simple visual indicator to readily quantify sample NA template. In addition, a companion microfluidic device for extracting plasma from whole blood without a centrifuge, generating cell-free plasma for chip-based molecular diagnostics, is described. Extensions to a myriad of related applications including, for example, food testing, cancer screening, and insect genotyping are briefly surveyed.",2015 Oct 20,"['Mauk, Michael G.', 'Liu, Changchun', 'Song, Jinzhao', 'Bau, Haim H.']",Microarrays (Basel),,,True
78c82f8e3198d5c95cbbcceabefddbe82e8f2442,PMC,"Prioritization of Zoonotic Diseases in Kenya, 2015",http://dx.doi.org/10.1371/journal.pone.0161576,PMC4996421,27557120,CC0,"INTRODUCTION: Zoonotic diseases have varying public health burden and socio-economic impact across time and geographical settings making their prioritization for prevention and control important at the national level. We conducted systematic prioritization of zoonotic diseases and developed a ranked list of these diseases that would guide allocation of resources to enhance their surveillance, prevention, and control. METHODS: A group of 36 medical, veterinary, and wildlife experts in zoonoses from government, research institutions and universities in Kenya prioritized 36 diseases using a semi-quantitative One Health Zoonotic Disease Prioritization tool developed by Centers for Disease Control and Prevention with slight adaptations. The tool comprises five steps: listing of zoonotic diseases to be prioritized, development of ranking criteria, weighting criteria by pairwise comparison through analytical hierarchical process, scoring each zoonotic disease based on the criteria, and aggregation of scores. RESULTS: In order of importance, the participants identified severity of illness in humans, epidemic/pandemic potential in humans, socio-economic burden, prevalence/incidence and availability of interventions (weighted scores assigned to each criteria were 0.23, 0.22, 0.21, 0.17 and 0.17 respectively), as the criteria to define the relative importance of the diseases. The top five priority diseases in descending order of ranking were anthrax, trypanosomiasis, rabies, brucellosis and Rift Valley fever. CONCLUSION: Although less prominently mentioned, neglected zoonotic diseases ranked highly compared to those with epidemic potential suggesting these endemic diseases cause substantial public health burden. The list of priority zoonotic disease is crucial for the targeted allocation of resources and informing disease prevention and control programs for zoonoses in Kenya.",2016 Aug 24,"['Munyua, Peninah', 'Bitek, Austine', 'Osoro, Eric', 'Pieracci, Emily G.', 'Muema, Josephat', 'Mwatondo, Athman', 'Kungu, Mathew', 'Nanyingi, Mark', 'Gharpure, Radhika', 'Njenga, Kariuki', 'Thumbi, Samuel M.']",PLoS One,,,True
1d6e09ce2559ff9fcb55f3351110880446b477fe,PMC,Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements,http://dx.doi.org/10.1371/journal.pntd.0004921,PMC4996428,27556644,CC BY,"BACKGROUND: There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses) replication. METHODOLOGY/PRINCIPAL FINDINGS: Seventy-nine novel RNA binding proteins for dengue virus (DENV) were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated. CONCLUSIONS/SIGNIFICANCE: The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps cellular proteins for efficient amplification.",2016 Aug 24,"['Viktorovskaya, Olga V.', 'Greco, Todd M.', 'Cristea, Ileana M.', 'Thompson, Sunnie R.']",PLoS Negl Trop Dis,,,True
60f0773c8eeace01dd0364c5c63febbfe9dd3a62,PMC,Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge,http://dx.doi.org/10.1371/journal.pone.0161169,PMC4996460,27556586,CC BY,"Dogs represent the most important domestic reservoir of L. chagasi (syn. L. infantum). A vaccine against canine visceral leishmaniasis (CVL) would be an important tool for decreasing the anxiety related to possible L. chagasi infection and for controlling human visceral leishmaniasis (VL). Because the sand fly salivary proteins are potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in past decades. We investigated the immunogenicity of the “LbSapSal” vaccine (L. braziliensis antigens, saponin as adjuvant, and Lutzomyia longipalpis salivary gland extract) in dogs at baseline (T(0)), during the post-vaccination protocol (T(3rd)) and after early (T(90)) and late (T(885)) times following L. chagasi-challenge. Our major data indicated that immunization with “LbSapSal” is able to induce biomarkers characterized by enhanced amounts of type I (tumor necrosis factor [TNF]-α, interleukin [IL]-12, interferon [IFN]-γ) cytokines and reduction in type II cytokines (IL-4 and TGF-β), even after experimental challenge. The establishment of a prominent pro-inflammatory immune response after “LbSapSal” immunization supported the increased levels of nitric oxide production, favoring a reduction in spleen parasitism (78.9%) and indicating long-lasting protection against L. chagasi infection. In conclusion, these results confirmed the hypothesis that the “LbSapSal” vaccination is a potential tool to control the Leishmania chagasi infection.",2016 Aug 24,"['Resende, Lucilene Aparecida', 'Aguiar-Soares, Rodrigo Dian de Oliveira', 'Gama-Ker, Henrique', 'Roatt, Bruno Mendes', 'de Mendonça, Ludmila Zanandreis', 'Alves, Marina Luiza Rodrigues', 'da Silveira-Lemos, Denise', 'Corrêa-Oliveira, Rodrigo', 'Martins-Filho, Olindo Assis', 'Araújo, Márcio Sobreira Silva', 'Fujiwara, Ricardo Toshio', 'Gontijo, Nelder Figueiredo', 'Reis, Alexandre Barbosa', 'Giunchetti, Rodolfo Cordeiro']",PLoS One,,,True
7aa69b98902425b5daeb3b1f647d067b8abf7157,PMC,"National Library of Medicine Disaster Information Management Research Center: Achieving the vision, 2010–2013",http://dx.doi.org/10.3233/ISU-140731,PMC4996476,27570333,CC BY,"From 2010 to 2013, the National Library of Medicine (NLM) Disaster Information Management Research Center (DIMRC) continued to build its programs and services on the foundation laid in its starting years, 2008–2010. Prior to 2008, NLM had a long history of providing health information, training, and tools in response to disasters. Aware of this legacy, the NLM long range plan (Charting a Course for the 21st Century: NLM’s Long Range Plan 2006–2016) called for creation of a center to show “a strong commitment to disaster remediation and to provide a platform for demonstrating how libraries and librarians can be part of the solution to this national problem”. NLM is continuing efforts to ensure that medical libraries have plans for the continuity of their operations, librarians are trained to understand their roles in preparedness and response, online disaster health information resources are available for many audiences and in multiple formats, and research is conducted on tools to enhance the exchange of critical information during and following disasters. This paper describes the 2010–2013 goals and activities of DIMRC and its future plans.",2014,"['Love, Cynthia B.', 'Arnesen, Stacey J.', 'Phillips, Steven J.', 'Windom, Robert E.']",Inf Serv Use,,,True
7b9a303570b221251e6281e20f70ecaa125c4e78,PMC,Expression of the NS5 (VPg) Protein of Murine Norovirus Induces a G1/S Phase Arrest,http://dx.doi.org/10.1371/journal.pone.0161582,PMC4996510,27556406,CC BY,"Murine norovirus-1 (MNV-1) is known to subvert host cell division inducing an accumulation of cells in the G(0)/G(1) phase, creating conditions where viral replication is favored. This study identified that NS5 (VPg), is capable of inducing cell cycle arrest in the absence of viral replication or other viral proteins in an analogous manner to MNV-1 infection. NS5 expression induced an accumulation of cells in the G(0)/G(1) phase in an asynchronous population by inhibiting progression at the G(1)/S restriction point. Furthermore, NS5 expression resulted in a down-regulation of cyclin A expression in asynchronous cells and inhibited cyclin A expression in cells progressing from G(1) to S phase. The activity of NS5 on the host cell cycle occurs through an uncharacterized function. Amino acid substitutions of NS5(Y26A) and NS5(F123A) that inhibit the ability for NS5 to attach to RNA and recruit host eukaryotic translation initiation factors, respectively, retained the ability to induce an accumulation of cells in the G(0)/G(1) phase as identified for wild-type NS5. To the best of our knowledge, this is the first report of a VPg protein manipulating the host cell cycle.",2016 Aug 24,"['Davies, Colin', 'Ward, Vernon K.']",PLoS One,,,True
417286ac22fc95bdfe96df0dc2a7c1e3eb5befe1,PMC,Evaluation of Low versus High Volume per Minute Displacement CO(2) Methods of Euthanasia in the Induction and Duration of Panic-Associated Behavior and Physiology,http://dx.doi.org/10.3390/ani6080045,PMC4997270,27490573,CC BY,"SIMPLE SUMMARY: Current recommendations for the use of CO(2) as a euthanasia agent for rats require the use of gradual fill methods in order to render the animal insensible prior to their experience of pain. However, there is concern that the use of these gradual fill methods may increase the distress experienced by these animals. We evaluated social and anxiety behavior of rats that had been exposed to concentrations of CO(2) that did not cause a loss of consciousness. We also evaluated the physiologic changes of rats that were euthanized with gradual fill protocols as compared to rapid fill methods. We found that rats exposed to concentrations of CO(2) that did not cause a loss of consciousness did exhibit increased anxiety and decreased social behavior. We also found that the use of a 10% volume per minute displacement rate of CO(2) resulted in physiologic and behavioral changes suggestive of distress. ABSTRACT: Current recommendations for the use of CO(2) as a euthanasia agent for rats require the use of gradual fill protocols (such as 10% to 30% volume displacement per minute) in order to render the animal insensible prior to exposure to levels of CO(2) that are associated with pain. However, exposing rats to CO(2), concentrations as low as 7% CO(2) are reported to cause distress and 10%–20% CO(2) induces panic-associated behavior and physiology, but loss of consciousness does not occur until CO(2) concentrations are at least 40%. This suggests that the use of the currently recommended low flow volume per minute displacement rates create a situation where rats are exposed to concentrations of CO(2) that induce anxiety, panic, and distress for prolonged periods of time. This study first characterized the response of male rats exposed to normoxic 20% CO(2) for a prolonged period of time as compared to room air controls. It demonstrated that rats exposed to this experimental condition displayed clinical signs consistent with significantly increased panic-associated behavior and physiology during CO(2) exposure. When atmospheric air was then again delivered, there was a robust increase in respiration rate that coincided with rats moving to the air intake. The rats exposed to CO(2) also displayed behaviors consistent with increased anxiety in the behavioral testing that followed the exposure. Next, this study assessed the behavioral and physiologic responses of rats that were euthanized with 100% CO(2) infused at 10%, 30%, or 100% volume per minute displacement rates. Analysis of the concentrations of CO(2) and oxygen in the euthanasia chamber and the behavioral responses of the rats suggest that the use of the very low flow volume per minute displacement rate (10%) may prolong the duration of panicogenic ranges of ambient CO(2), while the use of the higher flow volume per minute displacement rate (100%) increases agitation. Therefore, of the volume displacement per minute rates evaluated, this study suggests that 30% minimizes the potential pain and distress experienced by the animal.",2016 Aug 2,"['Hickman, Debra L.', 'Fitz, Stephanie D.', 'Bernabe, Cristian S.', 'Caliman, Izabela F.', 'Haulcomb, Melissa M.', 'Federici, Lauren M.', 'Shekhar, Anantha', 'Johnson, Philip L.']",Animals (Basel),,,True
f8f5d842db3bc80e5c22011583b8e965abfe624c,PMC,Chinese Public Attention to the Outbreak of Ebola in West Africa: Evidence from the Online Big Data Platform,http://dx.doi.org/10.3390/ijerph13080780,PMC4997466,27527196,CC BY,"Objective: The outbreak of the Ebola epidemic in West Africa in 2014 exerted enormous global public reaction via the Internet and social media. This study aimed to investigate and evaluate the public reaction to Ebola in China and identify the primitive correlation between possible influence factors caused by the outbreak of Ebola in West Africa and Chinese public attention via Internet surveillance. Methods: Baidu Index (BDI) and Sina Micro Index (SMI) were collected from their official websites, and the disease-related data were recorded from the websites of the World Health Organization (WHO), U.S. Centers for Disease Control and Prevention (CDC), and U.S. National Ministries of Health. The average BDI of Internet users in different regions were calculated to identify the public reaction to the Ebola outbreak. Spearman’s rank correlation was used to check the relationship of epidemic trends with BDI and SMI. Additionally, spatio-temporal analysis and autocorrelation analysis were performed to detect the clustered areas with the high attention to the topic of “Ebola”. The related news reports were collected from authoritative websites to identify potential patterns. Results: The BDI and the SMI for “Ebola” showed a similar fluctuating trend with a correlation coefficient = 0.9 (p < 0.05). The average BDI in Beijing, Tibet, and Shanghai was higher than other cities. However, the disease-related indicators did not identify potential correlation with both indices above. A hotspot area was detected in Tibet by local autocorrelation analysis. The most likely cluster identified by spatiotemporal cluster analysis was in the northeast regions of China with the relative risk (RR) of 2.26 (p ≤ 0.01) from 30 July to 14 August in 2014. Qualitative analysis indicated that negative news could lead to a continuous increase of the public’s attention until the appearance of a positive news report. Conclusions: Confronted with the risk of cross-border transmission of the infectious disease, online surveillance might be used as an innovative approach to perform public communication and health education through examining the public’s reaction and attitude.",2016 Aug 3,"['Liu, Kui', 'Li, Li', 'Jiang, Tao', 'Chen, Bin', 'Jiang, Zhenggang', 'Wang, Zhengting', 'Chen, Yongdi', 'Jiang, Jianmin', 'Gu, Hua']",Int J Environ Res Public Health,,,True
f243e05a2d51029218e0c313b20fa57c65104a62,PMC,Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications,http://dx.doi.org/10.3390/v8080206,PMC4997570,27490565,CC BY,"The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration (FDA)-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice. As provided, clomiphene is, approximately, a 60:40 mixture of two stereoisomers, enclomiphene and zuclomiphene. The pharmacokinetic properties of the two isomers vary, but both accumulate in the eye and male reproductive tract, tissues in which EBOV can persist. Here we compared the ability of clomiphene and its isomers to inhibit EBOV using viral-like particle (VLP) entry and transcription/replication-competent VLP (trVLP) assays. Clomiphene and its isomers inhibited the entry and infection of VLPs and trVLPs with similar potencies. This was demonstrated with VLPs bearing the glycoproteins from three filoviruses (EBOV Mayinga, EBOV Makona, and Marburg virus) and in two cell lines (293T/17 and Vero E6). Visual problems have been noted in EBOV survivors, and viral RNA has been isolated from semen up to nine months post-infection. Since the clomiphene isomers accumulate in these affected tissues, clomiphene or one of its isomers warrants consideration as an anti-EBOV agent, for example, to potentially help ameliorate symptoms in EBOV survivors.",2016 Aug 2,"['Nelson, Elizabeth A.', 'Barnes, Alyson B.', 'Wiehle, Ronald D.', 'Fontenot, Gregory K.', 'Hoenen, Thomas', 'White, Judith M.']",Viruses,,,True
b4609f3760031ac126473d8438bdebc4df596be0,PMC,"Inoculation of Goats, Sheep, and Horses with MERS-CoV Does Not Result in Productive Viral Shedding",http://dx.doi.org/10.3390/v8080230,PMC4997592,27548203,CC BY,"The Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized in 2012 and can cause severe disease in infected humans. Dromedary camels are the reservoir for the virus, although, other than nasal discharge, these animals do not display any overt clinical disease. Data from in vitro experiments suggest that other livestock such as sheep, goats, and horses might also contribute to viral transmission, although field data has not identified any seropositive animals. In order to understand if these animals could be infected, we challenged young goats and horses and adult sheep with MERS-CoV by intranasal inoculation. Minimal or no virus shedding was detected in all of the animals. During the four weeks following inoculation, neutralizing antibodies were detected in the young goats, but not in sheep or horses.",2016 Aug 19,"['Adney, Danielle R.', 'Brown, Vienna R.', 'Porter, Stephanie M.', 'Bielefeldt-Ohmann, Helle', 'Hartwig, Airn E.', 'Bowen, Richard A.']",Viruses,,,True
7bfb902f2434b4667d48f2fcb5a1d7233acda4c5,PMC,Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells,http://dx.doi.org/10.1038/srep32288,PMC4997611,27558873,CC BY,"Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection.",2016 Aug 25,"['Ruiz Silva, Mariana', 'van der Ende-Metselaar, Heidi', 'Mulder, H. Lie', 'Smit, Jolanda M.', 'Rodenhuis-Zybert, Izabela A.']",Sci Rep,,,True
c10cefdc314bbd0702d8d8ced268caad9ae818fb,PMC,Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells,http://dx.doi.org/10.1038/srep32288,PMC4997611,27558873,CC BY,"Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection.",2016 Aug 25,"['Ruiz Silva, Mariana', 'van der Ende-Metselaar, Heidi', 'Mulder, H. Lie', 'Smit, Jolanda M.', 'Rodenhuis-Zybert, Izabela A.']",Sci Rep,,,False
be9cb78bf2453f68b260e9ed4f75d9ceccb77754,PMC,Lower serum uric acid level predicts mortality in dialysis patients,http://dx.doi.org/10.1097/MD.0000000000003701,PMC4998435,27310949,CC BY,"We evaluated the impact of serum uric acid (SUA) on mortality in patients with chronic dialysis. A total of 4132 adult patients on dialysis were enrolled prospectively between August 2008 and September 2014. Among them, we included 1738 patients who maintained dialysis for at least 3 months and had available SUA in the database. We categorized the time averaged-SUA (TA-SUA) into 5 groups: <5.5, 5.5–6.4, 6.5–7.4, 7.5–8.4, and ≥8.5 mg/dL. Cox regression analysis was used to calculate the hazard ratio (HR) of all-cause mortality according to SUA group. The mean TA-SUA level was slightly higher in men than in women. Patients with lower TA-SUA level tended to have lower body mass index (BMI), phosphorus, serum albumin level, higher proportion of diabetes mellitus (DM), and higher proportion of malnourishment on the subjective global assessment (SGA). During a median follow-up of 43.9 months, 206 patients died. Patients with the highest SUA had a similar risk to the middle 3 TA-SUA groups, but the lowest TA-SUA group had a significantly elevated HR for mortality. The lowest TA-SUA group was significantly associated with increased all-cause mortality (adjusted HR, 1.720; 95% confidence interval, 1.007–2.937; P = 0.047) even after adjusting for demographic, comorbid, nutritional covariables, and medication use that could affect SUA levels. This association was prominent in patients with well nourishment on the SGA, a preserved serum albumin level, a higher BMI, and concomitant DM although these parameters had no significant interaction in the TA-SUA-mortality relationship except DM. In conclusion, a lower TA-SUA level <5.5 mg/dL predicted all-cause mortality in patients with chronic dialysis.",2016 Jun 17,"['Bae, Eunjin', 'Cho, Hyun-Jeong', 'Shin, Nara', 'Kim, Sun Moon', 'Yang, Seung Hee', 'Kim, Dong Ki', 'Kim, Yong-Lim', 'Kang, Shin-Wook', 'Yang, Chul Woo', 'Kim, Nam Ho', 'Kim, Yon Su', 'Lee, Hajeong']",Medicine (Baltimore),,,True
8602709a812146a012e16df450b991f6343d2f46,PMC,Suppression of Virulent Porcine Epidemic Diarrhea Virus Proliferation by the PI3K/Akt/GSK-3α/β Pathway,http://dx.doi.org/10.1371/journal.pone.0161508,PMC4999130,27560518,CC BY,"Porcine epidemic diarrhea virus (PEDV) has recently caused high mortality in suckling piglets with subsequent large economic losses to the swine industry. Many intracellular signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, are activated by viral infection. The PI3K/Akt pathway is an important cellular pathway that has been shown to be required for virus replication. In the present study, we found that the PEDV JS-2013 strain activated Akt in Vero cells at early (5–15 min) and late stages (8–10 h) of infection. Inhibiting PI3K, an upstream activator of Akt, enhanced PEDV replication. Inhibiting GSK-3α/β, one of the downstream effectors of PI3K/Akt pathway and regulated by Akt during PEDV infected Vero cells, also enhanced PEDV replication. Collectively, our data suggest that PI3K/Akt/GSK-3α/β signaling pathway is activated by PEDV and functions in inhibiting PEDV replication.",2016 Aug 25,"['Kong, Ning', 'Wu, Yongguang', 'Meng, Qiong', 'Wang, Zhongze', 'Zuo, Yewen', 'Pan, Xi', 'Tong, Wu', 'Zheng, Hao', 'Li, Guoxin', 'Yang, Shen', 'Yu, Hai', 'Zhou, En-min', 'Shan, Tongling', 'Tong, Guangzhi']",PLoS One,,,True
9ef23d86bba041d9fc573624cdf17e94a30fb8f6,PMC,"Molecular epidemiology and characterization of human coronavirus in Thailand, 2012–2013",http://dx.doi.org/10.1186/s40064-016-3101-9,PMC4999384,27625974,CC BY,"BACKGROUND: Coronavirus causes respiratory infections in humans. To determine the prevalence of human coronavirus (HCoV) infection among patients with influenza-like illness, 5833 clinical samples from nasopharyngeal swabs and aspirates collected between January 2012 and December 2013 were examined. RESULTS: HCoV was found in 46 (0.79 %) samples. There were 19 (0.32 %) HCoV-HKU1, 19 (0.32 %) HCoV-NL63, 5 (0.09 %) HCoV-229E, and 3 (0.05 %) HCoV-OC43. None of the sample tested positive for MERS-CoV. The majority (54 %) of the HCoV-positive patients were between the ages of 0 and 5 years. HCoV was detected throughout the 2-year period and generally peaked from May to October, which coincided with the rainy season. Phylogenetic trees based on the alignment of the spike (S) gene sequences suggest an emergence of a new clade for HCoV-229E. CONCLUSIONS: The data in this study provide an insight into the prevalence of the recent circulating HCoVs in the region.",2016 Aug 26,"['Soonnarong, Rapeepun', 'Thongpan, Ilada', 'Payungporn, Sunchai', 'Vuthitanachot, Chanpim', 'Vuthitanachot, Viboonsuk', 'Vichiwattana, Preeyaporn', 'Vongpunsawad, Sompong', 'Poovorawan, Yong']",Springerplus,,,True
74de948d0adbf472ee959b8521f40fb4a5aa034a,PMC,Moonshot Science—Risks and Benefits,http://dx.doi.org/10.1128/mBio.01381-16,PMC4999558,27578761,CC BY,"Ever since the successful Apollo 11 Moon landing in 1969, a “moonshot” has come to signify a bold effort to achieve a seemingly impossible task. The Obama administration recently called for a moonshot to cure cancer, an initiative that has elicited mixed responses from researchers who welcome additional funding but worry about raising expectations. We suggest that a successful moonshot requires a sufficient understanding of the basic science underlying a problem in question so that efforts can be focused on engineering a solution. Current gaps in our basic knowledge of cancer biology make the cancer moonshot a uniquely challenging endeavor. Nevertheless, history has shown that intensive research efforts have frequently yielded conceptual and technological breakthroughs with unanticipated benefits for society. We expect that this effort will be no different.",2016 Aug 30,"['Casadevall, Arturo', 'Fang, Ferric C.']",mBio,,,True
ec0b7ac5c69486b4c914cf362fc49e176f401516,PMC,CD8 T Cell–Independent Antitumor Response and Its Potential for Treatment of Malignant Gliomas,http://dx.doi.org/10.3390/cancers8080071,PMC4999780,27472363,CC BY,"Malignant brain tumors continue to represent a devastating diagnosis with no real chance for cure. Despite an increasing list of potential salvage therapies, standard-of-care for these patients has not changed in over a decade. Immunotherapy has been seen as an exciting option, with the potential to offer specific and long lasting tumor clearance. The “gold standard” in immunotherapy has been the development of a tumor-specific CD8 T cell response to potentiate tumor clearance and immunological memory. While many advances have been made in the field of immunotherapy, few therapies have seen true success. Many of the same principles used to develop immunotherapy in tumors of the peripheral organs have been applied to brain tumor immunotherapy. The immune-specialized nature of the brain should call into question whether this approach is appropriate. Recent results from our own experiments require a rethinking of current dogma. Perhaps a CD8 T cell response is not sufficient for an organ as immunologically unique as the brain. Examination of previously elucidated principles of the brain’s immune-specialized status and known immunological preferences should generate discussion and experimentation to address the failure of current therapies.",2016 Jul 27,"['Murphy, Katherine A.', 'Griffith, Thomas S.']",Cancers (Basel),,,True
3691c1e9130028008093d3d62e16a43883631cae,PMC,An Old Solution for a New Problem: Antiserum against Emerging Infectious Diseases,http://dx.doi.org/10.3389/fpubh.2016.00178,PMC5000394,27617259,CC BY,,2016 Aug 26,"Morais, Victor",Front Public Health,,,True
caadc408ff1144a53369c7e0f63634ff264be9ee,PMC,Evaluation of a new community-based curriculum in disaster medicine for undergraduates,http://dx.doi.org/10.1186/s12909-016-0746-6,PMC5000399,27562428,CC BY,"BACKGROUND: Nowadays, many medical schools include training in disaster medicine in undergraduate studies. This study evaluated the efficacy of a disaster medicine curriculum recently designed for Saudi Arabian medical students. METHODS: Participants were 15 male and 14 female students in their fourth, fifth or sixth year at Jazan University Medical School, Saudi Arabia. The course was held at the Research Center in Emergency and Disaster Medicine and Computer Sciences Applied to the Medical Practice in Novara, Italy. RESULTS: The overall mean score on a test given before the course was 41.0 % and it increased to 67.7 % on the post-test (Wilcoxon test for paired samples: z = 4.71, p < 0.0001). There were no significant differences between the mean scores of males and females, or between students in their fourth, fifth or sixth year of medical school. CONCLUSIONS: These results show that this curriculum is effective for teaching disaster medicine to undergraduate medical students. Adoption of this course would help to increase the human resources available for dealing with disaster situations.",2016 Aug 26,"['Bajow, Nidaa', 'Djalali, Ahmadreza', 'Ingrassia, Pier Luigi', 'Ragazzoni, Luca', 'Ageely, Hussein', 'Bani, Ibrahim', 'Corte, Francesco Della']",BMC Med Educ,,,True
c8f60c136e1ace8011a2ee3844510d862ff9053a,PMC,Risk of MERS importation and onward transmission: a systematic review and analysis of cases reported to WHO,http://dx.doi.org/10.1186/s12879-016-1787-5,PMC5000488,27562369,CC BY,"BACKGROUND: The continuing circulation of MERS in the Middle East makes the international dissemination of the disease a permanent threat. To inform risk assessment, we investigated the spatiotemporal pattern of MERS global dissemination and looked for factors explaining the heterogeneity observed in transmission events following importation. METHODS: We reviewed imported MERS cases worldwide up to July 2015. We modelled importations in time based on air travel combined with incidence in Middle East. We used the detailed history of MERS case management after importation (time to hospitalization and isolation, number of hospitals visited,…) in logistic regression to identify risk factors for secondary transmission. We assessed changes in time to hospitalization and isolation in relation to collective and public health attention to the epidemic, measured by three indicators (Google Trends, ProMED-mail, Disease Outbreak News). RESULTS: Modelled importation events were found to reproduce both the temporal and geographical structure of those observed – the Pearson correlation coefficient between predicted and observed monthly time series was large (r = 0.78, p < 10(−4)). The risk of secondary transmission following importation increased with the time to case isolation or death (OR = 1.7 p = 0.04) and more precisely with the duration of hospitalization (OR = 1.7, p = 0.02). The average daily number of secondary cases was 0.02 [0.0,0.12] in the community and 0.20 [0.03,9.0] in the hospital. Time from hospitalisation to isolation decreased in periods of high public health attention (2.33 ± 0.34 vs. 6.44 ± 0.97 days during baseline attention). CONCLUSIONS: Countries at risk of importation should focus their resources on strict infection control measures for the management of potential cases in healthcare settings and on prompt MERS cases identification. Individual and collective awareness are key to substantially improve such preparedness. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1787-5) contains supplementary material, which is available to authorized users.",2016 Aug 25,"['Poletto, Chiara', 'Boëlle, Pierre-Yves', 'Colizza, Vittoria']",BMC Infect Dis,,,True
3c20c596797997337c0e8ed472cf7847dc467c65,PMC,Risk of MERS importation and onward transmission: a systematic review and analysis of cases reported to WHO,http://dx.doi.org/10.1186/s12879-016-1787-5,PMC5000488,27562369,CC BY,"BACKGROUND: The continuing circulation of MERS in the Middle East makes the international dissemination of the disease a permanent threat. To inform risk assessment, we investigated the spatiotemporal pattern of MERS global dissemination and looked for factors explaining the heterogeneity observed in transmission events following importation. METHODS: We reviewed imported MERS cases worldwide up to July 2015. We modelled importations in time based on air travel combined with incidence in Middle East. We used the detailed history of MERS case management after importation (time to hospitalization and isolation, number of hospitals visited,…) in logistic regression to identify risk factors for secondary transmission. We assessed changes in time to hospitalization and isolation in relation to collective and public health attention to the epidemic, measured by three indicators (Google Trends, ProMED-mail, Disease Outbreak News). RESULTS: Modelled importation events were found to reproduce both the temporal and geographical structure of those observed – the Pearson correlation coefficient between predicted and observed monthly time series was large (r = 0.78, p < 10(−4)). The risk of secondary transmission following importation increased with the time to case isolation or death (OR = 1.7 p = 0.04) and more precisely with the duration of hospitalization (OR = 1.7, p = 0.02). The average daily number of secondary cases was 0.02 [0.0,0.12] in the community and 0.20 [0.03,9.0] in the hospital. Time from hospitalisation to isolation decreased in periods of high public health attention (2.33 ± 0.34 vs. 6.44 ± 0.97 days during baseline attention). CONCLUSIONS: Countries at risk of importation should focus their resources on strict infection control measures for the management of potential cases in healthcare settings and on prompt MERS cases identification. Individual and collective awareness are key to substantially improve such preparedness. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1787-5) contains supplementary material, which is available to authorized users.",2016 Aug 25,"['Poletto, Chiara', 'Boëlle, Pierre-Yves', 'Colizza, Vittoria']",BMC Infect Dis,,,True
b0691ba288acf449186c899b08788d6b4a2ecdeb,PMC,Biochemical and genetic analysis of the role of the viral polymerase in enterovirus recombination,http://dx.doi.org/10.1093/nar/gkw567,PMC5001610,27317698,CC BY,"Genetic recombination in single-strand, positive-sense RNA viruses is a poorly understand mechanism responsible for generating extensive genetic change and novel phenotypes. By moving a critical cis-acting replication element (CRE) from the polyprotein coding region to the 3′ non-coding region we have further developed a cell-based assay (the 3′CRE-REP assay) to yield recombinants throughout the non-structural coding region of poliovirus from dually transfected cells. We have additionally developed a defined biochemical assay in which the only protein present is the poliovirus RNA dependent RNA polymerase (RdRp), which recapitulates the strand transfer events of the recombination process. We have used both assays to investigate the role of the polymerase fidelity and nucleotide turnover rates in recombination. Our results, of both poliovirus intertypic and intratypic recombination in the CRE-REP assay and using a range of polymerase variants in the biochemical assay, demonstrate that RdRp fidelity is a fundamental determinant of recombination frequency. High fidelity polymerases exhibit reduced recombination and low fidelity polymerases exhibit increased recombination in both assays. These studies provide the basis for the analysis of poliovirus recombination throughout the non-structural region of the virus genome and provide a defined biochemical assay to further dissect this important evolutionary process.",2016 Aug 19,"['Woodman, Andrew', 'Arnold, Jamie\xa0J.', 'Cameron, Craig\xa0E.', 'Evans, David\xa0J.']",Nucleic Acids Res,,,True
5ebbe85f2c617784f1c7880858b0374263c87b57,PMC,Biochemical and genetic analysis of the role of the viral polymerase in enterovirus recombination,http://dx.doi.org/10.1093/nar/gkw567,PMC5001610,27317698,CC BY,"Genetic recombination in single-strand, positive-sense RNA viruses is a poorly understand mechanism responsible for generating extensive genetic change and novel phenotypes. By moving a critical cis-acting replication element (CRE) from the polyprotein coding region to the 3′ non-coding region we have further developed a cell-based assay (the 3′CRE-REP assay) to yield recombinants throughout the non-structural coding region of poliovirus from dually transfected cells. We have additionally developed a defined biochemical assay in which the only protein present is the poliovirus RNA dependent RNA polymerase (RdRp), which recapitulates the strand transfer events of the recombination process. We have used both assays to investigate the role of the polymerase fidelity and nucleotide turnover rates in recombination. Our results, of both poliovirus intertypic and intratypic recombination in the CRE-REP assay and using a range of polymerase variants in the biochemical assay, demonstrate that RdRp fidelity is a fundamental determinant of recombination frequency. High fidelity polymerases exhibit reduced recombination and low fidelity polymerases exhibit increased recombination in both assays. These studies provide the basis for the analysis of poliovirus recombination throughout the non-structural region of the virus genome and provide a defined biochemical assay to further dissect this important evolutionary process.",2016 Aug 19,"['Woodman, Andrew', 'Arnold, Jamie\xa0J.', 'Cameron, Craig\xa0E.', 'Evans, David\xa0J.']",Nucleic Acids Res,,,False
630a94063d188ceeb2302472ac2e1a0da2e31216,PMC,Consecutive Inhibition of ISG15 Expression and ISGylation by Cytomegalovirus Regulators,http://dx.doi.org/10.1371/journal.ppat.1005850,PMC5001722,27564865,CC BY,"Interferon-stimulated gene 15 (ISG15) encodes an ubiquitin-like protein that covalently conjugates protein. Protein modification by ISG15 (ISGylation) is known to inhibit the replication of many viruses. However, studies on the viral targets and viral strategies to regulate ISGylation-mediated antiviral responses are limited. In this study, we show that human cytomegalovirus (HCMV) replication is inhibited by ISGylation, but the virus has evolved multiple countermeasures. HCMV-induced ISG15 expression was mitigated by IE1, a viral inhibitor of interferon signaling, however, ISGylation was still strongly upregulated during virus infection. RNA interference of UBE1L (E1), UbcH8 (E2), Herc5 (E3), and UBP43 (ISG15 protease) revealed that ISGylation inhibits HCMV growth by downregulating viral gene expression and virion release in a manner that is more prominent at low multiplicity of infection. A viral regulator pUL26 was found to interact with ISG15, UBE1L, and Herc5, and be ISGylated. ISGylation of pUL26 regulated its stability and inhibited its activities to suppress NF-κB signaling and complement the growth of UL26-null mutant virus. Moreover, pUL26 reciprocally suppressed virus-induced ISGylation independent of its own ISGylation. Consistently, ISGylation was more pronounced in infections with the UL26-deleted mutant virus, whose growth was more sensitive to IFNβ treatment than that of the wild-type virus. Therefore, pUL26 is a viral ISG15 target that also counteracts ISGylation. Our results demonstrate that ISGylation inhibits HCMV growth at multiple steps and that HCMV has evolved countermeasures to suppress ISG15 transcription and protein ISGylation, highlighting the importance of the interplay between virus and ISGylation in productive viral infection.",2016 Aug 26,"['Kim, Ye Ji', 'Kim, Eui Tae', 'Kim, Young-Eui', 'Lee, Myoung Kyu', 'Kwon, Ki Mun', 'Kim, Keun Il', 'Stamminger, Thomas', 'Ahn, Jin-Hyun']",PLoS Pathog,,,True
421ee1f936a1714743c3cf06be01220009624a03,PMC,Analysis of Spatiotemporal Characteristics of Pandemic SARS Spread in Mainland China,http://dx.doi.org/10.1155/2016/7247983,PMC5002496,27597972,CC BY,"Severe acute respiratory syndrome (SARS) is one of the most severe emerging infectious diseases of the 21st century so far. SARS caused a pandemic that spread throughout mainland China for 7 months, infecting 5318 persons in 194 administrative regions. Using detailed mainland China epidemiological data, we study spatiotemporal aspects of this person-to-person contagious disease and simulate its spatiotemporal transmission dynamics via the Bayesian Maximum Entropy (BME) method. The BME reveals that SARS outbreaks show autocorrelation within certain spatial and temporal distances. We use BME to fit a theoretical covariance model that has a sine hole spatial component and exponential temporal component and obtain the weights of geographical and temporal autocorrelation factors. Using the covariance model, SARS dynamics were estimated and simulated under the most probable conditions. Our study suggests that SARS transmission varies in its epidemiological characteristics and SARS outbreak distributions exhibit palpable clusters on both spatial and temporal scales. In addition, the BME modelling demonstrates that SARS transmission features are affected by spatial heterogeneity, so we analyze potential causes. This may benefit epidemiological control of pandemic infectious diseases.",2016 Aug 15,"['Cao, Chunxiang', 'Chen, Wei', 'Zheng, Sheng', 'Zhao, Jian', 'Wang, Jinfeng', 'Cao, Wuchun']",Biomed Res Int,,,True
ebf25663cfe4314966c86a48ba4ce6a04a435760,PMC,Diminazene Aceturate Improves Cardiac Fibrosis and Diastolic Dysfunction in Rats with Kidney Disease,http://dx.doi.org/10.1371/journal.pone.0161760,PMC5003360,27571511,CC BY,"Angiotensin converting enzyme (ACE) 2 is a negative regulator of the renin angiotensin system (RAS) through its role to degrade angiotensin II. In rats with subtotal nephrectomy (STNx), adverse cardiac remodelling occurs despite elevated cardiac ACE2 activity. We hypothesised that diminazene aceturate (DIZE), which has been described as having an off-target effect to activate ACE2, would have beneficial cardiac effects in STNx rats. STNx led to hypertension, diastolic dysfunction, left ventricular hypertrophy, cardiac fibrosis, and increased cardiac ACE, ACE2, Ang II and Ang 1–7 levels. Cardiac gene expression of ADAM17 was also increased. In STNx, two-weeks of subcutaneous DIZE (15mg/kg/d) had no effect on blood pressure but improved diastolic dysfunction and cardiac fibrosis, reduced ADAM17 mRNA and shifted the cardiac RAS balance to a cardioprotective profile with reduced ACE and Ang II. There was no change in cardiac ACE2 activity or in cardiac Ang 1–7 levels with DIZE. In conclusion, our results suggest that DIZE exerts a protective effect on the heart under the pathological condition of kidney injury. This effect was not due to improved kidney function, a fall in blood pressure or a reduction in LVH but was associated with a reduction in cardiac ACE and cardiac Ang II levels. As in vitro studies showed no direct effect of DIZE on ACE2 or ACE activity, the precise mechanism of action of DIZE remains to be determined.",2016 Aug 29,"['Velkoska, Elena', 'Patel, Sheila K.', 'Griggs, Karen', 'Burrell, Louise M.']",PLoS One,,,True
3e72fd7554ad263eefddd4a0c6ee06afea606a44,PMC,Microarray for Identification of the Chiropteran Host Species of Rabies Virus in Canada,http://dx.doi.org/10.3390/microarrays2020153,PMC5003475,27605186,CC BY,"Species identification through genetic barcoding can augment traditional taxonomic methods, which rely on morphological features of the specimen. Such approaches are especially valuable when specimens are in poor condition or comprise very limited material, a situation that often applies to chiropteran (bat) specimens submitted to the Canadian Food Inspection Agency for rabies diagnosis. Coupled with phenotypic plasticity of many species and inconclusive taxonomic keys, species identification using only morphological traits can be challenging. In this study, a microarray assay with associated PCR of the mitochondrial cytochrome c oxidase subunit I (COI) gene was developed for differentiation of 14 bat species submitted to the Canadian Food Inspection Agency from 1985–2012 for rabies diagnosis. The assay was validated with a reference collection of DNA from 153 field samples, all of which had been barcoded previously. The COI gene from 152 samples which included multiple specimens of each target species were successfully amplified by PCR and accurately identified by the microarray. One sample that was severely decomposed failed to amplify with PCR primers developed in this study, but amplified weakly after switching to alternate primers and was accurately typed by the microarray. Thus, the chiropteran microarray was able to accurately differentiate between the 14 species of Canadian bats targeted. This PCR and microarray assay would allow unequivocal identification to species of most, if not all, bat specimens submitted for rabies diagnosis in Canada.",2013 May 31,"['Lung, Oliver', 'Nadin-Davis, Susan', 'Fisher, Mathew', 'Erickson, Anthony', 'Knowles, M. Kimberly', 'Furukawa-Stoffer, Tara', 'Ambagala, Aruna']",Microarrays (Basel),,,True
9287f4bf129f205faa654f47a2fb9a8af8a9526a,PMC,Subcellular redistribution and sequential recruitment of macromolecular components during SGIV assembly,http://dx.doi.org/10.1007/s13238-016-0292-3,PMC5003786,27430948,CC BY,"Virus infection consists of entry, synthesis of macromolecular components, virus assembly and release. Understanding of the mechanisms underlying each event is necessary for the intervention of virus infection in human healthcare and agriculture. Here we report the visualization of Singapore grouper iridovirus (SGIV) assembly in the medaka haploid embryonic stem (ES) cell line HX1. SGIV is a highly infectious DNA virus that causes a massive loss in marine aquaculture. Ectopic expression of VP88GFP, a fusion between green fluorescent protein and the envelope protein VP088, did not compromise the ES cell properties and susceptibility to SGIV infection. Although VP88GFP disperses evenly in the cytoplasm of non-infected cells, it undergoes aggregation and redistribution in SGIV-infected cells. Real-time visualization revealed multiple key stages of VP88GFP redistribution and the dynamics of viral assembly site (VAS). Specifically, VP88GFP entry into and condensation in the VAS occurred within a 6-h duration, a similar duration was observed also for the release of VP88GFP-containing SGIV out of the cell. Taken together, VP088 is an excellent marker for visualizing the SGIV infection process. Our results provide new insight into macromolecular component recruitment and SGIV assembly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-016-0292-3) contains supplementary material, which is available to authorized users.",2016 Sep 18,"['Yuan, Yongming', 'Hong, Yunhan']",Protein Cell,,,False
43fcca53a2dc667a4f8898dc2880d461bcbfbcff,PMC,Subcellular redistribution and sequential recruitment of macromolecular components during SGIV assembly,http://dx.doi.org/10.1007/s13238-016-0292-3,PMC5003786,27430948,CC BY,"Virus infection consists of entry, synthesis of macromolecular components, virus assembly and release. Understanding of the mechanisms underlying each event is necessary for the intervention of virus infection in human healthcare and agriculture. Here we report the visualization of Singapore grouper iridovirus (SGIV) assembly in the medaka haploid embryonic stem (ES) cell line HX1. SGIV is a highly infectious DNA virus that causes a massive loss in marine aquaculture. Ectopic expression of VP88GFP, a fusion between green fluorescent protein and the envelope protein VP088, did not compromise the ES cell properties and susceptibility to SGIV infection. Although VP88GFP disperses evenly in the cytoplasm of non-infected cells, it undergoes aggregation and redistribution in SGIV-infected cells. Real-time visualization revealed multiple key stages of VP88GFP redistribution and the dynamics of viral assembly site (VAS). Specifically, VP88GFP entry into and condensation in the VAS occurred within a 6-h duration, a similar duration was observed also for the release of VP88GFP-containing SGIV out of the cell. Taken together, VP088 is an excellent marker for visualizing the SGIV infection process. Our results provide new insight into macromolecular component recruitment and SGIV assembly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-016-0292-3) contains supplementary material, which is available to authorized users.",2016 Sep 18,"['Yuan, Yongming', 'Hong, Yunhan']",Protein Cell,,,False
0529ed2074b15413b032e82de1fcce37efde51a2,PMC,Subcellular redistribution and sequential recruitment of macromolecular components during SGIV assembly,http://dx.doi.org/10.1007/s13238-016-0292-3,PMC5003786,27430948,CC BY,"Virus infection consists of entry, synthesis of macromolecular components, virus assembly and release. Understanding of the mechanisms underlying each event is necessary for the intervention of virus infection in human healthcare and agriculture. Here we report the visualization of Singapore grouper iridovirus (SGIV) assembly in the medaka haploid embryonic stem (ES) cell line HX1. SGIV is a highly infectious DNA virus that causes a massive loss in marine aquaculture. Ectopic expression of VP88GFP, a fusion between green fluorescent protein and the envelope protein VP088, did not compromise the ES cell properties and susceptibility to SGIV infection. Although VP88GFP disperses evenly in the cytoplasm of non-infected cells, it undergoes aggregation and redistribution in SGIV-infected cells. Real-time visualization revealed multiple key stages of VP88GFP redistribution and the dynamics of viral assembly site (VAS). Specifically, VP88GFP entry into and condensation in the VAS occurred within a 6-h duration, a similar duration was observed also for the release of VP88GFP-containing SGIV out of the cell. Taken together, VP088 is an excellent marker for visualizing the SGIV infection process. Our results provide new insight into macromolecular component recruitment and SGIV assembly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-016-0292-3) contains supplementary material, which is available to authorized users.",2016 Sep 18,"['Yuan, Yongming', 'Hong, Yunhan']",Protein Cell,,,True
7fa2f5a443163614e02fa7b7d7c89fa535dc7b23,PMC,Tick-borne encephalitis virus induces chemokine RANTES expression via activation of IRF-3 pathway,http://dx.doi.org/10.1186/s12974-016-0665-9,PMC5004318,27576490,CC BY,"BACKGROUND: Tick-borne encephalitis virus (TBEV) is one of the most important flaviviruses that targets the central nervous system (CNS) and causes encephalitides in humans. Although neuroinflammatory mechanisms may contribute to brain tissue destruction, the induction pathways and potential roles of specific chemokines in TBEV-mediated neurological disease are poorly understood. METHODS: BALB/c mice were intracerebrally injected with TBEV, followed by evaluation of chemokine and cytokine profiles using protein array analysis. The virus-infected mice were treated with the CC chemokine antagonist Met-RANTES or anti-RANTES mAb to determine the role of RANTES in affecting TBEV-induced neurological disease. The underlying signaling mechanisms were delineated using RANTES promoter luciferase reporter assay, siRNA-mediated knockdown, and pharmacological inhibitors in human brain-derived cell culture models. RESULTS: In a mouse model, pathological features including marked inflammatory cell infiltrates were observed in brain sections, which correlated with a robust up-regulation of RANTES within the brain but not in peripheral tissues and sera. Antagonizing RANTES within CNS extended the survival of mice and reduced accumulation of infiltrating cells in the brain after TBEV infection. Through in vitro studies, we show that virus infection up-regulated RANTES production at both mRNA and protein levels in human brain-derived cell lines and primary progenitor-derived astrocytes. Furthermore, IRF-3 pathway appeared to be essential for TBEV-induced RANTES production. Site mutation of an IRF-3-binding motif abrogated the RANTES promoter activity in virus-infected brain cells. Moreover, IRF-3 was activated upon TBEV infection as evidenced by phosphorylation of TBK1 and IRF-3, while blockade of IRF-3 activation drastically reduced virus-induced RANTES expression. CONCLUSIONS: Our findings together provide insights into the molecular mechanism underlying RANTES production induced by TBEV, highlighting its potential importance in the process of neuroinflammatory responses to TBEV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-016-0665-9) contains supplementary material, which is available to authorized users.",2016 Aug 30,"['Zhang, Xiaowei', 'Zheng, Zhenhua', 'Liu, Xijuan', 'Shu, Bo', 'Mao, Panyong', 'Bai, Bingke', 'Hu, Qinxue', 'Luo, Minhua', 'Ma, Xiaohe', 'Cui, Zongqiang', 'Wang, Hanzhong']",J Neuroinflammation,,,True
514a5ab6c1549c33d8acf502b929bc0699f5e21c,PMC,"Human Respiratory Coronaviruses Detected In Patients with Influenza-Like Illness in Arkansas, USA",http://dx.doi.org/10.4172/2161-0517.S2-004,PMC5004774,27588218,CC BY,"Acute respiratory viruses often result in significant morbidity and mortality. The potential impact of human respiratory coronavirus (CoV) infections was underestimated until the severe acute respiratory syndrome (SARS-CoV) outbreak in 2003, which showed that new, highly pathogenic coronaviruses could be introduced to humans, highlighting the importance of monitoring the circulating coronaviruses. The use of sensitive molecular methods has contributed to the differential diagnosis of viruses circulating in humans. Our study aim was to investigate the molecular epidemiology of human CoV strains circulating in Arkansas, their genetic variability and their association with reported influenza-like symptoms. We analyzed 200 nasal swab samples, collected by the Arkansas Department of Health in 2010, for influenza diagnosis. All samples were from patients showing acute respiratory symptoms while testing negative for influenza. Samples were pre-screened, using a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) multiprobe for coronavirus, and subjected to confirmatory pancoronavirus and/or strain-specific reverse transcriptase (RT)-PCR followed by sequence analysis. Seventy-nine samples (39.5%) were positive by qRT-PCR and 35 samples (17.5%) were confirmed by conventional RT-PCR. Twenty-three of the confirmed samples (59%) were sequenced. The most frequent strain detected was HCoV-OC43-like followed by NL63-like; only one sample was positive for HCoV-229E and one for HCoV-HKU1. Feline-like CoV strains were detected in three samples, representing possible evidence of interspecies transmission or a new human strain. Seventeen percent of the coronavirus positive samples were also positive for other respiratory viruses, such as Respiratory Syncytial Virus (RSV), Parainfluenza 2 and 3, and Rhinovirus. Thus, HCoV-OC43, NL63, HKU1 and new feline-like strains were circulating in Arkansas in 2010. HCoV was the sole respiratory virus detected in 16% of the patients who showed acute respiratory symptoms with negative diagnoses for influenza virus.",2014 Dec 26,"['Silva, Camila S', 'Mullis, Lisa B', 'Pereira, Olavo', 'Saif, Linda J', 'Vlasova, Anastasia', 'Zhang, Xuming', 'Owens, Randall J', 'Paulson, Dale', 'Taylor, Deborah', 'Haynes, Lia M', 'Azevedo, Marli P']",Virol Mycol,,,True
82bf46aebd99e6e67368b9c789d01e561ed147af,PMC,High-Throughput Sequencing-Based Immune Repertoire Study during Infectious Disease,http://dx.doi.org/10.3389/fimmu.2016.00336,PMC5005336,27630639,CC BY,"The selectivity of the adaptive immune response is based on the enormous diversity of T and B cell antigen-specific receptors. The immune repertoire, the collection of T and B cells with functional diversity in the circulatory system at any given time, is dynamic and reflects the essence of immune selectivity. In this article, we review the recent advances in immune repertoire study of infectious diseases, which were achieved by traditional techniques and high-throughput sequencing (HTS) techniques. HTS techniques enable the determination of complementary regions of lymphocyte receptors with unprecedented efficiency and scale. This progress in methodology enhances the understanding of immunologic changes during pathogen challenge and also provides a basis for further development of novel diagnostic markers, immunotherapies, and vaccines.",2016 Aug 31,"['Hou, Dongni', 'Chen, Cuicui', 'Seely, Eric John', 'Chen, Shujing', 'Song, Yuanlin']",Front Immunol,,,True
4ea1d124972eda4c488d6446f88964f60bed47fc,PMC,Changes in the Transcriptome of Human Astrocytes Accompanying Oxidative Stress-Induced Senescence,http://dx.doi.org/10.3389/fnagi.2016.00208,PMC5005348,27630559,CC BY,"Aging is a major risk factor for many neurodegenerative disorders. A key feature of aging biology that may underlie these diseases is cellular senescence. Senescent cells accumulate in tissues with age, undergo widespread changes in gene expression, and typically demonstrate altered, pro-inflammatory profiles. Astrocyte senescence has been implicated in neurodegenerative disease, and to better understand senescence-associated changes in astrocytes, we investigated changes in their transcriptome using RNA sequencing. Senescence was induced in human fetal astrocytes by transient oxidative stress. Brain-expressed genes, including those involved in neuronal development and differentiation, were downregulated in senescent astrocytes. Remarkably, several genes indicative of astrocytic responses to injury were also downregulated, including glial fibrillary acidic protein and genes involved in the processing and presentation of antigens by major histocompatibility complex class II proteins, while pro-inflammatory genes were upregulated. Overall, our findings suggest that senescence-related changes in the function of astrocytes may impact the pathogenesis of age-related brain disorders.",2016 Aug 31,"['Crowe, Elizabeth P.', 'Tuzer, Ferit', 'Gregory, Brian D.', 'Donahue, Greg', 'Gosai, Sager J.', 'Cohen, Justin', 'Leung, Yuk Y.', 'Yetkin, Emre', 'Nativio, Raffaella', 'Wang, Li-San', 'Sell, Christian', 'Bonini, Nancy M.', 'Berger, Shelley L.', 'Johnson, F. Brad', 'Torres, Claudio']",Front Aging Neurosci,,,True
53db274f4427f9f421959b5d0e6b5dc47c58612a,PMC,Type I IFN Signaling Is Dispensable during Secondary Viral Infection,http://dx.doi.org/10.1371/journal.ppat.1005861,PMC5006979,27580079,CC BY,"Innate immune responses in general, and type I interferons (T1IFNs) in particular, play an important and often essential role during primary viral infections, by directly combatting the virus and by maximizing the primary adaptive immune response. Several studies have suggested that T1IFNs also contribute very substantially to the secondary (recall) response; they are thought (i) to be required to drive the early attrition of memory T cells, (ii) to support the subsequent expansion of surviving virus-specific memory cells, and (iii) to assist in the suppression and clearance of the infectious agent. However, many of these observations were predicated upon models in which T1IFN signaling was interrupted prior to a primary immune response, raising the possibility that the resulting memory cells might be intrinsically abnormal. We have directly addressed this by using an inducible-Cre model system in which the host remains genetically-intact during the primary response to infection, and in which T1IFN signaling can be effectively ablated prior to secondary viral challenge. We report that, in stark contrast to primary infection, T1IFN signaling is not required during the recall response. IFNαβR-deficient memory CD8(+) and CD4(+) memory T cells undergo attrition and expansion with kinetics that are indistinguishable from those of receptor-sufficient cells. Moreover, even in the absence of functional T1IFN signaling, the host’s immune capacity to rapidly suppress, and then to eradicate, a secondary infection remains intact. Thus, this study shows that T1IFN signaling is dispensable during the recall response to a virus infection. Moreover, two broader implications may be drawn. First, a T cell’s requirement for a cytokine is highly dependent on the cell’s maturation / differentiation status. Consequently, second, these data underscore the importance of evaluating a gene’s impact by modulating its expression or function in a temporally-controllable manner.",2016 Aug 31,"['Hosking, Martin P.', 'Flynn, Claudia T.', 'Whitton, J. Lindsay']",PLoS Pathog,,,True
237cdea88e640a5848e7abb82992894618315d63,PMC,The Occupational Risk of Influenza A (H1N1) Infection among Healthcare Personnel during the 2009 Pandemic: A Systematic Review and Meta-Analysis of Observational Studies,http://dx.doi.org/10.1371/journal.pone.0162061,PMC5006982,27579923,CC BY,"INTRODUCTION: The aim of this review was to record systematically and assess the published literature relating to the occupational risk of influenza A (H1N1) infection among healthcare personnel during the 2009 pandemic. METHODS: The literature search was performed in June 2015. An update was carried out in May 2016. It was applied to the electronic databases EMBASE, MEDLINE, PsycINFO, PubMed, CINAHL and Google Scholar. The quality assessment was conducted with a tool using eight criteria. A meta-analysis was carried out to compute pooled effect estimates for influenza A (H1N1) infection. RESULTS: A total of 26 studies were included in the review, 15 studies met the criteria for the meta-analysis. After a sensitivity analysis the pooled analysis showed a significantly increased odds for influenza A (H1N1) infection for healthcare personnel compared to controls/comparisons (OR = 2.08, 95% CI = 1.73 to 2.51). The pooled prevalence rate for healthcare personnel alone was 6.3%. CONCLUSIONS: This review corroborates the assumption that healthcare personnel were particularly at risk of influenza A (H1N1) infection during the 2009 pandemic. Healthcare facilities should intensify their focus on strategies to prevent infections among healthcare personnel, especially during the first period of pandemics.",2016 Aug 31,"['Lietz, Janna', 'Westermann, Claudia', 'Nienhaus, Albert', 'Schablon, Anja']",PLoS One,,,True
e80998b803a0a3a554bf0a0f923f65df16d7a1df,PMC,The Occupational Risk of Influenza A (H1N1) Infection among Healthcare Personnel during the 2009 Pandemic: A Systematic Review and Meta-Analysis of Observational Studies,http://dx.doi.org/10.1371/journal.pone.0162061,PMC5006982,27579923,CC BY,"INTRODUCTION: The aim of this review was to record systematically and assess the published literature relating to the occupational risk of influenza A (H1N1) infection among healthcare personnel during the 2009 pandemic. METHODS: The literature search was performed in June 2015. An update was carried out in May 2016. It was applied to the electronic databases EMBASE, MEDLINE, PsycINFO, PubMed, CINAHL and Google Scholar. The quality assessment was conducted with a tool using eight criteria. A meta-analysis was carried out to compute pooled effect estimates for influenza A (H1N1) infection. RESULTS: A total of 26 studies were included in the review, 15 studies met the criteria for the meta-analysis. After a sensitivity analysis the pooled analysis showed a significantly increased odds for influenza A (H1N1) infection for healthcare personnel compared to controls/comparisons (OR = 2.08, 95% CI = 1.73 to 2.51). The pooled prevalence rate for healthcare personnel alone was 6.3%. CONCLUSIONS: This review corroborates the assumption that healthcare personnel were particularly at risk of influenza A (H1N1) infection during the 2009 pandemic. Healthcare facilities should intensify their focus on strategies to prevent infections among healthcare personnel, especially during the first period of pandemics.",2016 Aug 31,"['Lietz, Janna', 'Westermann, Claudia', 'Nienhaus, Albert', 'Schablon, Anja']",PLoS One,,,False
31cc00c5c0a5298a2e22068195971a9e5f3a4fe4,PMC,The Occupational Risk of Influenza A (H1N1) Infection among Healthcare Personnel during the 2009 Pandemic: A Systematic Review and Meta-Analysis of Observational Studies,http://dx.doi.org/10.1371/journal.pone.0162061,PMC5006982,27579923,CC BY,"INTRODUCTION: The aim of this review was to record systematically and assess the published literature relating to the occupational risk of influenza A (H1N1) infection among healthcare personnel during the 2009 pandemic. METHODS: The literature search was performed in June 2015. An update was carried out in May 2016. It was applied to the electronic databases EMBASE, MEDLINE, PsycINFO, PubMed, CINAHL and Google Scholar. The quality assessment was conducted with a tool using eight criteria. A meta-analysis was carried out to compute pooled effect estimates for influenza A (H1N1) infection. RESULTS: A total of 26 studies were included in the review, 15 studies met the criteria for the meta-analysis. After a sensitivity analysis the pooled analysis showed a significantly increased odds for influenza A (H1N1) infection for healthcare personnel compared to controls/comparisons (OR = 2.08, 95% CI = 1.73 to 2.51). The pooled prevalence rate for healthcare personnel alone was 6.3%. CONCLUSIONS: This review corroborates the assumption that healthcare personnel were particularly at risk of influenza A (H1N1) infection during the 2009 pandemic. Healthcare facilities should intensify their focus on strategies to prevent infections among healthcare personnel, especially during the first period of pandemics.",2016 Aug 31,"['Lietz, Janna', 'Westermann, Claudia', 'Nienhaus, Albert', 'Schablon, Anja']",PLoS One,,,True
94f96f58a3d4328d9e1af3aba7ed1b8660689191,PMC,The Occupational Risk of Influenza A (H1N1) Infection among Healthcare Personnel during the 2009 Pandemic: A Systematic Review and Meta-Analysis of Observational Studies,http://dx.doi.org/10.1371/journal.pone.0162061,PMC5006982,27579923,CC BY,"INTRODUCTION: The aim of this review was to record systematically and assess the published literature relating to the occupational risk of influenza A (H1N1) infection among healthcare personnel during the 2009 pandemic. METHODS: The literature search was performed in June 2015. An update was carried out in May 2016. It was applied to the electronic databases EMBASE, MEDLINE, PsycINFO, PubMed, CINAHL and Google Scholar. The quality assessment was conducted with a tool using eight criteria. A meta-analysis was carried out to compute pooled effect estimates for influenza A (H1N1) infection. RESULTS: A total of 26 studies were included in the review, 15 studies met the criteria for the meta-analysis. After a sensitivity analysis the pooled analysis showed a significantly increased odds for influenza A (H1N1) infection for healthcare personnel compared to controls/comparisons (OR = 2.08, 95% CI = 1.73 to 2.51). The pooled prevalence rate for healthcare personnel alone was 6.3%. CONCLUSIONS: This review corroborates the assumption that healthcare personnel were particularly at risk of influenza A (H1N1) infection during the 2009 pandemic. Healthcare facilities should intensify their focus on strategies to prevent infections among healthcare personnel, especially during the first period of pandemics.",2016 Aug 31,"['Lietz, Janna', 'Westermann, Claudia', 'Nienhaus, Albert', 'Schablon, Anja']",PLoS One,,,False
266e97136335f2ef19dd7d372fe0472afa2af17c,PMC,Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses,http://dx.doi.org/10.1371/journal.ppat.1005817,PMC5007037,27579713,CC BY,"Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine-induced antibodies and therapeutic antibodies will enable a better understanding of their capacity to prevent and/or control HIV-1 infection in vivo.",2016 Aug 31,"['Tay, Matthew Zirui', 'Liu, Pinghuang', 'Williams, LaTonya D.', 'McRaven, Michael D', 'Sawant, Sheetal', 'Gurley, Thaddeus C', 'Xu, Thomas T.', 'Dennison, S. Moses', 'Liao, Hua-Xin', 'Chenine, Agnès-Laurence', 'Alam, S. Munir', 'Moody, M. Anthony', 'Hope, Thomas J.', 'Haynes, Barton F.', 'Tomaras, Georgia D.']",PLoS Pathog,,,True
67139d212b2529bb07805e78304619d373dd35d9,PMC,"Economic burden and its associated factors of hospitalized patients infected with A (H7N9) virus: a retrospective study in Eastern China, 2013–2014",http://dx.doi.org/10.1186/s40249-016-0170-5,PMC5007809,27580946,CC BY,"BACKGROUND: H7N9 continues to cause human infections and remains a pandemic concern. Understanding the economic impacts of this novel disease is important for making decisions on health resource allocation, including infectious disease prevention and control investment. However, there are limited data on such impacts. METHODS: Hospitalized laboratory-confirmed H7N9 patients or their families in Jiangsu Province of China were interviewed. Patients’ direct medical costs of hospitalization were derived from their hospital bills. A generalized linear model was employed to estimate the mean direct medical costs of patients with different characteristics. RESULTS: The mean direct cost of hospitalization for H7N9 was estimated to be ¥ 71 060 (95 % CI, 48 180–104 820), i.e., US$ 10 996 (95 % CI, 7 455–16 220), and was ¥12 060 (US$ 1 861), ¥136 120 (US$ 21 001) and ¥218 610 (US$ 33 728) for those who had mild or severe symptoms or who died, respectively. The principal components of the total fees differed among patients with different disease severity, although medication fees were always the largest contributors. Disease severity, proportion of reimbursement and family member monthly average income were identified as the key factors that contributed to a patient’s direct medical cost of hospitalization. CONCLUSIONS: The direct medical costs of hospitalized patients with H7N9 are significant, and far surpass the annual per capita income of Jiangsu Province, China. The influencing factors identified should be taken into account when developing related health insurance policies and making health resource allocation. TRIAL REGISTRATION: Not applicable. This is a survey study with no health care intervention implemented on human participants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0170-5) contains supplementary material, which is available to authorized users.",2016 Sep 1,"['Huo, Xiang', 'Chen, Li-Ling', 'Hong, Lei', 'Xiang, Lun-Hui', 'Tang, Fen-Yang', 'Chen, Shan-Hui', 'Gao, Qiang', 'Chen, Cong', 'Dai, Qi-gang', 'Sun, Chuan-Wu', 'Xu, Ke', 'Dai, Wen-Jun', 'Qi, Xian', 'Li, Chang-Cheng', 'Yu, Hui-Yan', 'Zhou, Yin', 'Huang, Hao-Di', 'Pan, Xing-Yang', 'Xu, Chang-sha', 'Zhou, Ming-Hao', 'Bao, Chang-Jun']",Infect Dis Poverty,,,False
bb6e40ae1720fa7008aa90c2c35d9d7e75c4611e,PMC,"Economic burden and its associated factors of hospitalized patients infected with A (H7N9) virus: a retrospective study in Eastern China, 2013–2014",http://dx.doi.org/10.1186/s40249-016-0170-5,PMC5007809,27580946,CC BY,"BACKGROUND: H7N9 continues to cause human infections and remains a pandemic concern. Understanding the economic impacts of this novel disease is important for making decisions on health resource allocation, including infectious disease prevention and control investment. However, there are limited data on such impacts. METHODS: Hospitalized laboratory-confirmed H7N9 patients or their families in Jiangsu Province of China were interviewed. Patients’ direct medical costs of hospitalization were derived from their hospital bills. A generalized linear model was employed to estimate the mean direct medical costs of patients with different characteristics. RESULTS: The mean direct cost of hospitalization for H7N9 was estimated to be ¥ 71 060 (95 % CI, 48 180–104 820), i.e., US$ 10 996 (95 % CI, 7 455–16 220), and was ¥12 060 (US$ 1 861), ¥136 120 (US$ 21 001) and ¥218 610 (US$ 33 728) for those who had mild or severe symptoms or who died, respectively. The principal components of the total fees differed among patients with different disease severity, although medication fees were always the largest contributors. Disease severity, proportion of reimbursement and family member monthly average income were identified as the key factors that contributed to a patient’s direct medical cost of hospitalization. CONCLUSIONS: The direct medical costs of hospitalized patients with H7N9 are significant, and far surpass the annual per capita income of Jiangsu Province, China. The influencing factors identified should be taken into account when developing related health insurance policies and making health resource allocation. TRIAL REGISTRATION: Not applicable. This is a survey study with no health care intervention implemented on human participants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0170-5) contains supplementary material, which is available to authorized users.",2016 Sep 1,"['Huo, Xiang', 'Chen, Li-Ling', 'Hong, Lei', 'Xiang, Lun-Hui', 'Tang, Fen-Yang', 'Chen, Shan-Hui', 'Gao, Qiang', 'Chen, Cong', 'Dai, Qi-gang', 'Sun, Chuan-Wu', 'Xu, Ke', 'Dai, Wen-Jun', 'Qi, Xian', 'Li, Chang-Cheng', 'Yu, Hui-Yan', 'Zhou, Yin', 'Huang, Hao-Di', 'Pan, Xing-Yang', 'Xu, Chang-sha', 'Zhou, Ming-Hao', 'Bao, Chang-Jun']",Infect Dis Poverty,,,True
cbc96926929c9fd4fe5e83928688041b3bdde491,PMC,Viral Manipulation of Host Inhibitory Receptor Signaling for Immune Evasion,http://dx.doi.org/10.1371/journal.ppat.1005776,PMC5008827,27584579,CC BY,,2016 Sep 1,"['Ong, Eugenia Z.', 'Chan, Kuan Rong', 'Ooi, Eng Eong']",PLoS Pathog,,,True
0cec675c685c32258b42e915ab84a45851b6dd26,PMC,Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use,http://dx.doi.org/10.1093/nar/gkw530,PMC5009743,27436286,CC BY,"Genetic decoding is not ‘frozen’ as was earlier thought, but dynamic. One facet of this is frameshifting that often results in synthesis of a C-terminal region encoded by a new frame. Ribosomal frameshifting is utilized for the synthesis of additional products, for regulatory purposes and for translational ‘correction’ of problem or ‘savior’ indels. Utilization for synthesis of additional products occurs prominently in the decoding of mobile chromosomal element and viral genomes. One class of regulatory frameshifting of stable chromosomal genes governs cellular polyamine levels from yeasts to humans. In many cases of productively utilized frameshifting, the proportion of ribosomes that frameshift at a shift-prone site is enhanced by specific nascent peptide or mRNA context features. Such mRNA signals, which can be 5′ or 3′ of the shift site or both, can act by pairing with ribosomal RNA or as stem loops or pseudoknots even with one component being 4 kb 3′ from the shift site. Transcriptional realignment at slippage-prone sequences also generates productively utilized products encoded trans-frame with respect to the genomic sequence. This too can be enhanced by nucleic acid structure. Together with dynamic codon redefinition, frameshifting is one of the forms of recoding that enriches gene expression.",2016 Sep 6,"['Atkins, John F.', 'Loughran, Gary', 'Bhatt, Pramod R.', 'Firth, Andrew E.', 'Baranov, Pavel V.']",Nucleic Acids Res,,,True
0cf083b09e13b9c6d8fe008590784d479f67f2f6,PMC,Low genetic diversity among historical and contemporary clinical isolates of felid herpesvirus 1,http://dx.doi.org/10.1186/s12864-016-3050-2,PMC5010698,27589862,CC BY,"BACKGROUND: Felid herpesvirus 1 (FHV-1) causes upper respiratory tract diseases in cats worldwide, including nasal and ocular discharge, conjunctivitis and oral ulceration. The nature and severity of disease can vary between clinical cases. Genetic determinants of virulence are likely to contribute to differences in the in vivo phenotype of FHV-1 isolates, but to date there have been limited studies investigating FHV-1 genetic diversity. This study used next generation sequencing to compare the genomes of contemporary Australian clinical isolates of FHV-1, vaccine isolates and historical clinical isolates, including isolates that predated the introduction of live attenuated vaccines into Australia. Analysis of the genome sequences aimed to assess the level of genetic diversity, identify potential genetic markers that could influence the in vivo phenotype of the isolates and examine the sequences for evidence of recombination. RESULTS: The full genome sequences of 26 isolates of FHV-1 were determined, including two vaccine isolates and 24 clinical isolates that were collected over a period of approximately 40 years. Analysis of the genome sequences revealed a remarkably low level of diversity (0.0–0.01 %) between the isolates. No potential genetic determinants of virulence were identified, but unique single nucleotide polymorphisms (SNPs) in the UL28 and UL44 genes were detected in the vaccine isolates that were not present in the clinical isolates. No evidence of FHV-1 recombination was detected using multiple methods of recombination detection, even though many of the isolates originated from cats housed in a shelter environment where high infective pressures were likely to exist. Evidence of displacement of dominant FHV-1 isolates with other (genetically distinct) FHV-1 isolates over time was observed amongst the isolates obtained from the shelter-housed animals. CONCLUSIONS: The results show that FHV-1 genomes are highly conserved. The lack of recombination detected in the FHV-1 genomes suggests that the risk of attenuated vaccines recombining to generate virulent field viruses is lower than has been suggested for some other herpesviruses. The SNPs detected only in the vaccine isolates offer the potential to develop PCR-based methods of differentiating vaccine and clinical isolates of FHV-1 in order to facilitate future epidemiological studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3050-2) contains supplementary material, which is available to authorized users.",2016 Sep 2,"['Vaz, Paola K.', 'Job, Natalie', 'Horsington, Jacquelyn', 'Ficorilli, Nino', 'Studdert, Michael J.', 'Hartley, Carol A.', 'Gilkerson, James R.', 'Browning, Glenn F.', 'Devlin, Joanne M.']",BMC Genomics,,,True
647652b31779d67fcdecf1848f7492b2ab10a4ee,PMC,High correlation of Middle East respiratory syndrome spread with Google search and Twitter trends in Korea,http://dx.doi.org/10.1038/srep32920,PMC5011762,27595921,CC BY,"The Middle East respiratory syndrome coronavirus (MERS-CoV) was exported to Korea in 2015, resulting in a threat to neighboring nations. We evaluated the possibility of using a digital surveillance system based on web searches and social media data to monitor this MERS outbreak. We collected the number of daily laboratory-confirmed MERS cases and quarantined cases from May 11, 2015 to June 26, 2015 using the Korean government MERS portal. The daily trends observed via Google search and Twitter during the same time period were also ascertained using Google Trends and Topsy. Correlations among the data were then examined using Spearman correlation analysis. We found high correlations (>0.7) between Google search and Twitter results and the number of confirmed MERS cases for the previous three days using only four simple keywords: “MERS”, “[Image: see text]” (“MERS (in Korean)”), “[Image: see text]” (“MERS symptoms (in Korean)”), and “[Image: see text]” (“MERS hospital (in Korean)”). Additionally, we found high correlations between the Google search and Twitter results and the number of quarantined cases using the above keywords. This study demonstrates the possibility of using a digital surveillance system to monitor the outbreak of MERS.",2016 Sep 6,"['Shin, Soo-Yong', 'Seo, Dong-Woo', 'An, Jisun', 'Kwak, Haewoon', 'Kim, Sung-Han', 'Gwack, Jin', 'Jo, Min-Woo']",Sci Rep,,,True
3f01163d7045653eac4e5ba5186c3444a358a594,PMC,High correlation of Middle East respiratory syndrome spread with Google search and Twitter trends in Korea,http://dx.doi.org/10.1038/srep32920,PMC5011762,27595921,CC BY,"The Middle East respiratory syndrome coronavirus (MERS-CoV) was exported to Korea in 2015, resulting in a threat to neighboring nations. We evaluated the possibility of using a digital surveillance system based on web searches and social media data to monitor this MERS outbreak. We collected the number of daily laboratory-confirmed MERS cases and quarantined cases from May 11, 2015 to June 26, 2015 using the Korean government MERS portal. The daily trends observed via Google search and Twitter during the same time period were also ascertained using Google Trends and Topsy. Correlations among the data were then examined using Spearman correlation analysis. We found high correlations (>0.7) between Google search and Twitter results and the number of confirmed MERS cases for the previous three days using only four simple keywords: “MERS”, “[Image: see text]” (“MERS (in Korean)”), “[Image: see text]” (“MERS symptoms (in Korean)”), and “[Image: see text]” (“MERS hospital (in Korean)”). Additionally, we found high correlations between the Google search and Twitter results and the number of quarantined cases using the above keywords. This study demonstrates the possibility of using a digital surveillance system to monitor the outbreak of MERS.",2016 Sep 6,"['Shin, Soo-Yong', 'Seo, Dong-Woo', 'An, Jisun', 'Kwak, Haewoon', 'Kim, Sung-Han', 'Gwack, Jin', 'Jo, Min-Woo']",Sci Rep,,,False
d0f0d83e31f3b077e623fc38a388fed8e8c1db3e,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,False
581f3f4246eb93bf7602fe189214bdcb1596cbfd,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,False
b00cbcd12b11a836fa85bf2c720e36fda7c91a1d,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,False
e436cf6b2d5bd9b2d9146b34f22301b0e4eb3747,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,False
15a1fc721871b0814cd07102842bbb982159a083,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,False
5da2a49bdb5d4cef0e9e918bcbf85d3f97dabd99,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,False
3de7d38c011f33930835b63043d70fb107a26700,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,False
940de307debf3a9042f73ef7cd17fa7a2464d408,PMC,"Viral deep sequencing needs an adaptive approach: IRMA, the iterative refinement meta-assembler",http://dx.doi.org/10.1186/s12864-016-3030-6,PMC5011931,27595578,CC BY,"BACKGROUND: Deep sequencing makes it possible to observe low-frequency viral variants and sub-populations with greater accuracy and sensitivity than ever before. Existing platforms can be used to multiplex a large number of samples; however, analysis of the resulting data is complex and involves separating barcoded samples and various read manipulation processes ending in final assembly. Many assembly tools were designed with larger genomes and higher fidelity polymerases in mind and do not perform well with reads derived from highly variable viral genomes. Reference-based assemblers may leave gaps in viral assemblies while de novo assemblers may struggle to assemble unique genomes. RESULTS: The IRMA (iterative refinement meta-assembler) pipeline solves the problem of viral variation by the iterative optimization of read gathering and assembly. As with all reference-based assembly, reads are included in assembly when they match consensus template sets; however, IRMA provides for on-the-fly reference editing, correction, and optional elongation without the need for additional reference selection. This increases both read depth and breadth. IRMA also focuses on quality control, error correction, indel reporting, variant calling and variant phasing. In fact, IRMA’s ability to detect and phase minor variants is one of its most distinguishing features. We have built modules for influenza and ebolavirus. We demonstrate usage and provide calibration data from mixture experiments. Methods for variant calling, phasing, and error estimation/correction have been redesigned to meet the needs of viral genomic sequencing. CONCLUSION: IRMA provides a robust next-generation sequencing assembly solution that is adapted to the needs and characteristics of viral genomes. The software solves issues related to the genetic diversity of viruses while providing customized variant calling, phasing, and quality control. IRMA is freely available for non-commercial use on Linux and Mac OS X and has been parallelized for high-throughput computing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3030-6) contains supplementary material, which is available to authorized users.",2016 Sep 5,"['Shepard, Samuel S.', 'Meno, Sarah', 'Bahl, Justin', 'Wilson, Malania M.', 'Barnes, John', 'Neuhaus, Elizabeth']",BMC Genomics,,,True
04c221e49d8355ce52360d5e37dc583f6502cc92,PMC,"In vitro antimicrobial activities of animal-used quinoxaline 1,4-di-N-oxides against mycobacteria, mycoplasma and fungi",http://dx.doi.org/10.1186/s12917-016-0812-7,PMC5011961,27600955,CC BY,"BACKGROUND: The quinoxaline 1,4-di-N-oxides (QdNOs) were known as potent antibacterial agents. For the purpose of evaluating the bioactivity of existing animal-used QdNOs drugs against representative pathogenic microorganism, the representative drugs of quinoxalines including cyadox, mequindox, quinocetone and their metabolites were submitted to the in vitro evaluation for antituberculosis, antimycoplasma, antifungal and antiviral activities. RESULTS: In antituberculosis assays, the prototype compounds were active (MIC = 4 ~ 8 μg/mL) against Mycobacterium tuberculosis H37Rv and M. bovis. Combined antimicrobial susceptibility test indicated that cyadox, mequindox and quinocetone combined with rifampicin had additive effect against M. tuberculosis complex with Fractional Inhibitory Concentration Index (FIC) of 0.75. Results of antifungal assays showed that quinocetone was active against Microsporum canis with MIC of 8 μg/mL. Antimycoplasma screening showed a generally good activity of quinocetone against Mycoplasma gallisepticum and Mycoplasma hyopneumoniae, with MIC between 8 and 16 μg/mL. As shown from the combined antimicrobial susceptibility test, cyadox, mequindox and quinocetone combined with tetracycline had additive effect against Mycoplasma gallisepticum with FIC of 0.75. These compounds were also submitted to antiviral assay against infectious bursal disease virus, porcine reproductive and respiratory syndrome virus, porcine parvovirus and classical swine fever virus. The results obtained showed that these QdNOs and their metabolites have no inhibitory activity against these viruses in vitro. CONCLUSIONS: QdNOs exhibit antimicrobial activities against mycobacteria, mycoplasma and fungi. This study gives new insight in further application of QdNOs and offers a way to promote the healthcare of animal husbandry. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0812-7) contains supplementary material, which is available to authorized users.",2016 Sep 6,"['Zhao, Yan', 'Cheng, Guyue', 'Hao, Haihong', 'Pan, Yuanhu', 'Liu, Zhenli', 'Dai, Menghong', 'Yuan, Zonghui']",BMC Vet Res,,,True
693a04c2c05485c6f19c6fc281ebf65dc4fe06dc,PMC,Molecular Biology and Infection of Hepatitis E Virus,http://dx.doi.org/10.3389/fmicb.2016.01419,PMC5013053,27656178,CC BY,"Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus.",2016 Sep 7,"['Nan, Yuchen', 'Zhang, Yan-Jin']",Front Microbiol,,,True
cc4ee2499ad533a2201243233dfbd178aa3b7185,PMC,CEACAM1: Expression and Role in Melanocyte Transformation,http://dx.doi.org/10.1155/2016/9406319,PMC5013198,27642217,CC BY,"Metastases represent the main cause of death in melanoma patients. Despite the current optimized targeted therapy or immune checkpoint inhibitors the treatment of metastatic melanoma is unsatisfactory. Because of the poor prognosis of advanced melanoma there is an urgent need to identify new biomarkers to differentiate melanoma cells from normal melanocytes, to stratify patients according to their risk, and to identify subgroups of patients that require close follow-up or more aggressive therapy. Furthermore, melanoma progression has been associated with the dysregulation of cell adhesion molecules. We have reviewed the literature and have discussed the important role of the expression of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in the development of melanoma. Thus, novel insights into CEACAM1 may lead to promising strategies in melanoma treatment, in monitoring melanoma patients, in assessing the response to immunotherapy, and in completing the standard immunohistochemical panel used in melanoma examination.",2016 Aug 24,"['Turcu, Gabriela', 'Nedelcu, Roxana Ioana', 'Ion, Daniela Adriana', 'Brînzea, Alice', 'Cioplea, Mirela Daniela', 'Jilaveanu, Lucia Beatrice', 'Zurac, Sabina Andrada']",Dis Markers,,,True
8f9e4f6b34a4b30f54abef008fc8c0fde00ff02f,PMC,"Bayesian uncertainty quantification for transmissibility of influenza, norovirus and Ebola using information geometry",http://dx.doi.org/10.1098/rsif.2016.0279,PMC5014059,27558850,CC BY,"Infectious diseases exert a large and in many contexts growing burden on human health, but violate most of the assumptions of classical epidemiological statistics and hence require a mathematically sophisticated approach. Viral shedding data are collected during human studies—either where volunteers are infected with a disease or where existing cases are recruited—in which the levels of live virus produced over time are measured. These have traditionally been difficult to analyse due to strong, complex correlations between parameters. Here, we show how a Bayesian approach to the inverse problem together with modern Markov chain Monte Carlo algorithms based on information geometry can overcome these difficulties and yield insights into the disease dynamics of two of the most prevalent human pathogens—influenza and norovirus—as well as Ebola virus disease.",2016 Aug,"['House, Thomas', 'Ford, Ashley', 'Lan, Shiwei', 'Bilson, Samuel', 'Buckingham-Jeffery, Elizabeth', 'Girolami, Mark']",J R Soc Interface,,,True
1292b5cdd7a8850cf1d0ceb1df706012c469da62,PMC,"Bayesian uncertainty quantification for transmissibility of influenza, norovirus and Ebola using information geometry",http://dx.doi.org/10.1098/rsif.2016.0279,PMC5014059,27558850,CC BY,"Infectious diseases exert a large and in many contexts growing burden on human health, but violate most of the assumptions of classical epidemiological statistics and hence require a mathematically sophisticated approach. Viral shedding data are collected during human studies—either where volunteers are infected with a disease or where existing cases are recruited—in which the levels of live virus produced over time are measured. These have traditionally been difficult to analyse due to strong, complex correlations between parameters. Here, we show how a Bayesian approach to the inverse problem together with modern Markov chain Monte Carlo algorithms based on information geometry can overcome these difficulties and yield insights into the disease dynamics of two of the most prevalent human pathogens—influenza and norovirus—as well as Ebola virus disease.",2016 Aug,"['House, Thomas', 'Ford, Ashley', 'Lan, Shiwei', 'Bilson, Samuel', 'Buckingham-Jeffery, Elizabeth', 'Girolami, Mark']",J R Soc Interface,,,True
6a1fd48435dc54d1682a0bafd6cdf7142b6b5bc4,PMC,Inferring R(0) in emerging epidemics—the effect of common population structure is small,http://dx.doi.org/10.1098/rsif.2016.0288,PMC5014060,27581480,CC BY,"When controlling an emerging outbreak of an infectious disease, it is essential to know the key epidemiological parameters, such as the basic reproduction number R(0) and the control effort required to prevent a large outbreak. These parameters are estimated from the observed incidence of new cases and information about the infectious contact structures of the population in which the disease spreads. However, the relevant infectious contact structures for new, emerging infections are often unknown or hard to obtain. Here, we show that, for many common true underlying heterogeneous contact structures, the simplification to neglect such structures and instead assume that all contacts are made homogeneously in the whole population results in conservative estimates for R(0) and the required control effort. This means that robust control policies can be planned during the early stages of an outbreak, using such conservative estimates of the required control effort.",2016 Aug,"['Trapman, Pieter', 'Ball, Frank', 'Dhersin, Jean-Stéphane', 'Tran, Viet Chi', 'Wallinga, Jacco', 'Britton, Tom']",J R Soc Interface,,,True
0b7de7591cf59d3b9e8f9db423431c0850eb0276,PMC,Inferring R(0) in emerging epidemics—the effect of common population structure is small,http://dx.doi.org/10.1098/rsif.2016.0288,PMC5014060,27581480,CC BY,"When controlling an emerging outbreak of an infectious disease, it is essential to know the key epidemiological parameters, such as the basic reproduction number R(0) and the control effort required to prevent a large outbreak. These parameters are estimated from the observed incidence of new cases and information about the infectious contact structures of the population in which the disease spreads. However, the relevant infectious contact structures for new, emerging infections are often unknown or hard to obtain. Here, we show that, for many common true underlying heterogeneous contact structures, the simplification to neglect such structures and instead assume that all contacts are made homogeneously in the whole population results in conservative estimates for R(0) and the required control effort. This means that robust control policies can be planned during the early stages of an outbreak, using such conservative estimates of the required control effort.",2016 Aug,"['Trapman, Pieter', 'Ball, Frank', 'Dhersin, Jean-Stéphane', 'Tran, Viet Chi', 'Wallinga, Jacco', 'Britton, Tom']",J R Soc Interface,,,True
cdb5b561f1c883eb82375c9c62550de77bc8b51e,PMC,"Editorial: A home for virology, ecology, epidemiology, and evolutionary biology",http://dx.doi.org/10.1093/ve/vev001,PMC5014471,27774275,CC BY,,2015 Mar 26,"['Elena, Santiago F.', 'Pybus, Oliver G.']",Virus Evol,,,True
d9ecb8e78616bebdb37e3b3b689ad60bafd922e3,PMC,Biochemical Characterization of Middle East Respiratory Syndrome Coronavirus Helicase,http://dx.doi.org/10.1128/mSphere.00235-16,PMC5014916,27631026,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) helicase is a superfamily 1 helicase containing seven conserved motifs. We have cloned, expressed, and purified a Strep-fused recombinant MERS-CoV nonstructural protein 13 (M-nsp13) helicase. Characterization of its biochemical properties showed that it unwound DNA and RNA similarly to severe acute respiratory syndrome CoV nsp13 (S-nsp13) helicase. We showed that M-nsp13 unwound in a 5′-to-3′ direction and efficiently unwound the partially duplex RNA substrates with a long loading strand relative to those of the RNA substrates with a short or no loading strand. Moreover, the K(m) of ATP for M-nsp13 is inversely proportional to the length of the 5′ loading strand of the partially duplex RNA substrates. Finally, we also showed that the rate of unwinding (ku) of M-nsp13 is directly proportional to the length of the 5′ loading strand of the partially duplex RNA substrate. These results provide insights that enhance our understanding of the biochemical properties of M-nsp13. IMPORTANCE Coronaviruses are known to cause a wide range of diseases in humans and animals. Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans in the Middle East, Europe, North Africa, and the United States of America. Helicases are motor proteins that catalyze the processive separation of double-stranded nucleic acids into two single-stranded nucleic acids by utilizing the energy derived from ATP hydrolysis. MERS-CoV helicase is one of the most important viral replication enzymes of this coronavirus. Herein, we report the first bacterial expression, enzyme purification, and biochemical characterization of MERS-CoV helicase. The knowledge obtained from this study might be used to identify an inhibitor of MERS-CoV replication, and the helicase might be used as a therapeutic target.",2016 Sep 7,"['Adedeji, Adeyemi O.', 'Lazarus, Hilary']",mSphere,,,True
810473f2145d2412461fb848c151c89a0630ca1d,PMC,Biochemical Characterization of Middle East Respiratory Syndrome Coronavirus Helicase,http://dx.doi.org/10.1128/mSphere.00235-16,PMC5014916,27631026,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) helicase is a superfamily 1 helicase containing seven conserved motifs. We have cloned, expressed, and purified a Strep-fused recombinant MERS-CoV nonstructural protein 13 (M-nsp13) helicase. Characterization of its biochemical properties showed that it unwound DNA and RNA similarly to severe acute respiratory syndrome CoV nsp13 (S-nsp13) helicase. We showed that M-nsp13 unwound in a 5′-to-3′ direction and efficiently unwound the partially duplex RNA substrates with a long loading strand relative to those of the RNA substrates with a short or no loading strand. Moreover, the K(m) of ATP for M-nsp13 is inversely proportional to the length of the 5′ loading strand of the partially duplex RNA substrates. Finally, we also showed that the rate of unwinding (ku) of M-nsp13 is directly proportional to the length of the 5′ loading strand of the partially duplex RNA substrate. These results provide insights that enhance our understanding of the biochemical properties of M-nsp13. IMPORTANCE Coronaviruses are known to cause a wide range of diseases in humans and animals. Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans in the Middle East, Europe, North Africa, and the United States of America. Helicases are motor proteins that catalyze the processive separation of double-stranded nucleic acids into two single-stranded nucleic acids by utilizing the energy derived from ATP hydrolysis. MERS-CoV helicase is one of the most important viral replication enzymes of this coronavirus. Herein, we report the first bacterial expression, enzyme purification, and biochemical characterization of MERS-CoV helicase. The knowledge obtained from this study might be used to identify an inhibitor of MERS-CoV replication, and the helicase might be used as a therapeutic target.",2016 Sep 7,"['Adedeji, Adeyemi O.', 'Lazarus, Hilary']",mSphere,,,False
f37275235174f60a5028e7d86859fecd6550f737,PMC,MicroRNA-155 enhances T cell trafficking and antiviral effector function in a model of coronavirus-induced neurologic disease,http://dx.doi.org/10.1186/s12974-016-0699-z,PMC5015201,27604627,CC BY,"BACKGROUND: MicroRNAs (miRNAs) are noncoding RNAs that modulate cellular gene expression, primarily at the post-transcriptional level. We sought to examine the functional role of miR-155 in a model of viral-induced neuroinflammation. METHODS: Acute encephalomyelitis and immune-mediated demyelination were induced by intracranial injection with the neurotropic JHM strain of mouse hepatitis virus (JHMV) into C57BL/6 miR-155(+/+) wildtype (WT) mice or miR-155(−/−) mice. Morbidity and mortality, viral load and immune cell accumulation in the CNS, and spinal cord demyelination were assessed at defined points post-infection. T cells harvested from infected mice were used to examine cytolytic activity, cytokine activity, and expression of certain chemokine receptors. To determine the impact of miR-155 on trafficking, T cells from infected WT or miR-155(−/−) mice were adoptively transferred into RAG1(−/−) mice, and T cell accumulation into the CNS was assessed using flow cytometry. Statistical significance was determined using the Mantel-Cox log-rank test or Student’s T tests. RESULTS: Compared to WT mice, JHMV-infected miR-155(−/−) mice developed exacerbated disease concomitant with increased morbidity/mortality and an inability to control viral replication within the CNS. In corroboration with increased susceptibility to disease, miR-155(−/−) mice had diminished CD8(+) T cell responses in terms of numbers, cytolytic activity, IFN-γ secretion, and homing to the CNS that corresponded with reduced expression of the chemokine receptor CXCR3. Both IFN-γ secretion and trafficking were impaired in miR-155(−/−), virus-specific CD4(+) T cells; however, expression of the chemokine homing receptors analyzed on CD4(+) cells was not affected. Except for very early during infection, there were not significant differences in macrophage infiltration into the CNS between WT and miR-155(−/−) JHMV-infected mice, and the severity of demyelination was similar at 14 days p.i. between WT and miR-155(−/−) JHMV-infected mice. CONCLUSIONS: These findings support a novel role for miR-155 in host defense in a model of viral-induced encephalomyelitis. Specifically, miR-155 enhances antiviral T cell responses including cytokine secretion, cytolytic activity, and homing to the CNS in response to viral infection. Further, miR-155 can play either a host-protective or host-damaging role during neuroinflammation depending on the disease trigger.",2016 Sep 7,"['Dickey, Laura L.', 'Worne, Colleen L.', 'Glover, Jessica L.', 'Lane, Thomas E.', 'O’Connell, Ryan M.']",J Neuroinflammation,,,True
41dc0a864ad331ec921ed5411bfdd3030859ac6f,PMC,Infectious diseases epidemic threats and mass gatherings: refocusing global attention on the continuing spread of the Middle East Respiratory syndrome coronavirus (MERS-CoV),http://dx.doi.org/10.1186/s12916-016-0686-3,PMC5015245,27604081,CC BY,"Media and World Health Organization (WHO) attention on Zika virus transmission at the 2016 Rio Olympic Games and the 2015 Ebola virus outbreak in West Africa diverted the attention of global public health authorities from other lethal infectious diseases with epidemic potential. Mass gatherings such as the annual Hajj pilgrimage hosted by Kingdom of Saudi Arabia attract huge crowds from all continents, creating high-risk conditions for the rapid global spread of infectious diseases. The highly lethal Middle Eastern respiratory syndrome coronavirus (MERS-CoV) remains in the WHO list of top emerging diseases likely to cause major epidemics. The 2015 MERS-CoV outbreak in South Korea, in which 184 MERS cases including 33 deaths occurred in 2 months, that was imported from the Middle East by a South Korean businessman was a wake-up call for the global community to refocus attention on MERS-CoV and other emerging and re-emerging infectious diseases with epidemic potential. The international donor community and Middle Eastern countries should make available resources for, and make a serious commitment to, taking forward a “One Health” global network for proactive surveillance, rapid detection, and prevention of MERS-CoV and other epidemic infectious diseases threats.",2016 Sep 7,"['Zumla, Alimuddin', 'Alagaili, Abdulaziz N.', 'Cotten, Matthew', 'Azhar, Esam I.']",BMC Med,,,True
1fceaf9f2102c71bf508ebd46c18c9b0cb48e6c3,PMC,"Morbidity, Mortality, and Seasonality of Influenza Hospitalizations in Egypt, November 2007-November 2014",http://dx.doi.org/10.1371/journal.pone.0161301,PMC5015910,27607330,CC0,"BACKGROUND: Influenza typically comprises a substantial portion of acute respiratory infections, a leading cause of mortality worldwide. However, influenza epidemiology data are lacking in Egypt. We describe seven years of Egypt’s influenza hospitalizations from a multi-site influenza surveillance system. METHODS: Syndromic case definitions identified individuals with severe acute respiratory infection (SARI) admitted to eight hospitals in Egypt. Standardized demographic and clinical data were collected. Nasopharyngeal and oropharyngeal swabs were tested for influenza using real-time reverse transcription polymerase chain reaction and typed as influenza A or B, and influenza A specimens subtyped. RESULTS: From November 2007–November 2014, 2,936/17,441 (17%) SARI cases were influenza-positive. Influenza-positive patients were more likely to be older, female, pregnant, and have chronic condition(s) (all p<0.05). Among them, 53 (2%) died, and death was associated with older age, five or more days from symptom onset to hospitalization, chronic condition(s), and influenza A (all p<0.05). An annual seasonal influenza pattern occurred from July–June. Each season, the proportion of the season’s influenza-positive cases peaked during November–May (19–41%). CONCLUSIONS: In Egypt, influenza causes considerable morbidity and mortality and influenza SARI hospitalization patterns mirror those of the Northern Hemisphere. Additional assessment of influenza epidemiology in Egypt may better guide disease control activities and vaccine policy.",2016 Sep 8,"['Kandeel, Amr', 'Dawson, Patrick', 'Labib, Manal', 'Said, Mayar', 'El-Refai, Samir', 'El-Gohari, Amani', 'Talaat, Maha']",PLoS One,,,True
e54d7c030edf8736b345a53ad17f7a7b00a74912,PMC,Negative pressure of the environmental air in the cleaning area of the materials and sterilization center: a systematic review,http://dx.doi.org/10.1590/1518-8345.1140.2781,PMC5016003,27598374,CC BY,"OBJECTIVE: to analyze the scientific evidence on aerosols generated during cleaning activities of health products in the Central Service Department (CSD) and the impact of the negative pressure of the ambient air in the cleaning area to control the dispersion of aerosols to adjacent areas. METHOD: for this literature systematic review the following searches were done: search guidelines, manuals or national and international technical standards given by experts; search in the portal and databases PubMed, Scopus, CINAHL and Web of Science; and a manual search of scientific articles. RESULTS: the five technical documents reviewed recommend that the CSD cleaning area should have a negative differential ambient air pressure, but scientific articles on the impact of this intervention were not found. The four articles included talked about aerosols formed after the use of a ultrasonic cleaner (an increased in the contamination especially during use) and pressurized water jet (formation of smaller aerosols 5μm). In a study, the aerosols formed from contaminated the hot tap water with Legionella pneumophila were evaluated. CONCLUSIONS: there is evidence of aerosol formation during cleanup activities in CSD. Studies on occupational diseases of respiratory origin of workers who work in CSD should be performed.",2016 Sep 1,"['Ciofi-Silva, Caroline Lopes', 'Hansen, Lisbeth Lima', 'Almeida, Alda Graciele Claudio dos Santos', 'Kawagoe, Julia Yaeko', 'Padoveze, Maria Clara', 'Graziano, Kazuko Uchikawa']",Rev Lat Am Enfermagem,,,True
4ed809f5b348f735454271411a4bef01bfad0734,PMC,The Quest for Anti-inflammatory and Anti-infective Biomaterials in Clinical Translation,http://dx.doi.org/10.3389/fbioe.2016.00071,PMC5016531,27668213,CC BY,"Biomaterials are now being used or evaluated clinically as implants to supplement the severe shortage of available human donor organs. To date, however, such implants have mainly been developed as scaffolds to promote the regeneration of failing organs due to old age or congenital malformations. In the real world, however, infection or immunological issues often compromise patients. For example, bacterial and viral infections can result in uncontrolled immunopathological damage and lead to organ failure. Hence, there is a need for biomaterials and implants that not only promote regeneration but also address issues that are specific to compromised patients, such as infection and inflammation. Different strategies are needed to address the regeneration of organs that have been damaged by infection or inflammation for successful clinical translation. Therefore, the real quest is for multifunctional biomaterials with combined properties that can combat infections, modulate inflammation, and promote regeneration at the same time. These strategies will necessitate the inclusion of methodologies for management of the cellular and signaling components elicited within the local microenvironment. In the development of such biomaterials, strategies range from the inclusion of materials that have intrinsic anti-inflammatory properties, such as the synthetic lipid polymer, 2-methacryloyloxyethyl phosphorylcholine (MPC), to silver nanoparticles that have antibacterial properties, to inclusion of nano- and micro-particles in biomaterials composites that deliver active drugs. In this present review, we present examples of both kinds of materials in each group along with their pros and cons. Thus, as a promising next generation strategy to aid or replace tissue/organ transplantation, an integrated smart programmable platform is needed for regenerative medicine applications to create and/or restore normal function at the cell and tissue levels. Therefore, now it is of utmost importance to develop integrative biomaterials based on multifunctional biopolymers and nanosystem for their practical and successful clinical translation.",2016 Sep 9,"['Griffith, May', 'Islam, Mohammad M.', 'Edin, Joel', 'Papapavlou, Georgia', 'Buznyk, Oleksiy', 'Patra, Hirak K.']",Front Bioeng Biotechnol,,,True
c45763bd83a192ce8ead3a628b11dd71b6e9c08a,PMC,"Zika virus: Epidemiology, current phobia and preparedness for upcoming mass gatherings, with examples from World Olympics and Pilgrimage",http://dx.doi.org/10.12669/pjms.324.10038,PMC5017074,27648063,CC BY,"OBJECTIVE: To describe Zika Virus (ZIKV) epidemiology, current phobia, and the required preparedness for its prevention during the upcoming Mass Gathering (MG) events. METHODS: Electronic databases of PubMed, WHO, CDC, Pan American Health Organization (PAHO), Google, and Cochrane library were extensively searched for ZIKV. Articles were reviewed, scrutinized and critically appraised and the most relevant articles were utilized. RESULTS: ZIKV is an emerging Flavivirus which was first isolated from Uganda in 1947. It is transmitted mainly through bite of Aedes mosquitoes. Sexual, perinatal and blood-borne transmissions are implicated. ZIKV is incriminated to cause microcephaly and Guillain-Barré syndrome. The spiky spread of ZIKV and its epidemic potential are especially problematic in countries which host big MGs with endogenous ZIKV circulation. This put millions of international travelers and local inhabitants at risk of acquiring ZIKV, especially in absence of vaccine until now. Brazil Olympic and Paralympics Games, and Muslims Hajj in Saudi Arabia are important upcoming MGs. Regarding Brazil, swiftly epidemic of ZIKV causes phobia and provokes claims and counter-claims about possible postponing or cancellation of such events. RECOMMENDATIONS: Intensifying ZIKV epidemiological surveillance (sentinel, syndromic, environmental, laboratory and electronic), and conduction of educational programs are required. Controlling Aedes vector (chemically & biologically) is essential. Multidisciplinary cooperation is required to win the war against ZIKV.",2016 Jul-Aug,"Ibrahim, Nahla Khamis",Pak J Med Sci,,,True
1af9746ea8f584f3f58da4f59d6dba8185f8be4b,PMC,Building Ventilation as an Effective Disease Intervention Strategy in a Dense Indoor Contact Network in an Ideal City,http://dx.doi.org/10.1371/journal.pone.0162481,PMC5017609,27611368,CC BY,"Emerging diseases may spread rapidly through dense and large urban contact networks, especially they are transmitted by the airborne route, before new vaccines can be made available. Airborne diseases may spread rapidly as people visit different indoor environments and are in frequent contact with others. We constructed a simple indoor contact model for an ideal city with 7 million people and 3 million indoor spaces, and estimated the probability and duration of contact between any two individuals during one day. To do this, we used data from actual censuses, social behavior surveys, building surveys, and ventilation measurements in Hong Kong to define eight population groups and seven indoor location groups. Our indoor contact model was integrated with an existing epidemiological Susceptible, Exposed, Infectious, and Recovered (SEIR) model to estimate disease spread and with the Wells-Riley equation to calculate local infection risks, resulting in an integrated indoor transmission network model. This model was used to estimate the probability of an infected individual infecting others in the city and to study the disease transmission dynamics. We predicted the infection probability of each sub-population under different ventilation systems in each location type in the case of a hypothetical airborne disease outbreak, which is assumed to have the same natural history and infectiousness as smallpox. We compared the effectiveness of controlling ventilation in each location type with other intervention strategies. We conclude that increasing building ventilation rates using methods such as natural ventilation in classrooms, offices, and homes is a relatively effective strategy for airborne diseases in a large city.",2016 Sep 9,"['Gao, Xiaolei', 'Wei, Jianjian', 'Lei, Hao', 'Xu, Pengcheng', 'Cowling, Benjamin J.', 'Li, Yuguo']",PLoS One,,,True
702157bbe24c5eca7ab92f90cd717c3e56aa6ccf,PMC,Building Ventilation as an Effective Disease Intervention Strategy in a Dense Indoor Contact Network in an Ideal City,http://dx.doi.org/10.1371/journal.pone.0162481,PMC5017609,27611368,CC BY,"Emerging diseases may spread rapidly through dense and large urban contact networks, especially they are transmitted by the airborne route, before new vaccines can be made available. Airborne diseases may spread rapidly as people visit different indoor environments and are in frequent contact with others. We constructed a simple indoor contact model for an ideal city with 7 million people and 3 million indoor spaces, and estimated the probability and duration of contact between any two individuals during one day. To do this, we used data from actual censuses, social behavior surveys, building surveys, and ventilation measurements in Hong Kong to define eight population groups and seven indoor location groups. Our indoor contact model was integrated with an existing epidemiological Susceptible, Exposed, Infectious, and Recovered (SEIR) model to estimate disease spread and with the Wells-Riley equation to calculate local infection risks, resulting in an integrated indoor transmission network model. This model was used to estimate the probability of an infected individual infecting others in the city and to study the disease transmission dynamics. We predicted the infection probability of each sub-population under different ventilation systems in each location type in the case of a hypothetical airborne disease outbreak, which is assumed to have the same natural history and infectiousness as smallpox. We compared the effectiveness of controlling ventilation in each location type with other intervention strategies. We conclude that increasing building ventilation rates using methods such as natural ventilation in classrooms, offices, and homes is a relatively effective strategy for airborne diseases in a large city.",2016 Sep 9,"['Gao, Xiaolei', 'Wei, Jianjian', 'Lei, Hao', 'Xu, Pengcheng', 'Cowling, Benjamin J.', 'Li, Yuguo']",PLoS One,,,True
ea007e00fc6123e617913bd68cd8b54c4f0b111a,PMC,Viral Infection of the Central Nervous System Exacerbates Interleukin-10 Receptor Deficiency-Mediated Colitis in SJL Mice,http://dx.doi.org/10.1371/journal.pone.0161883,PMC5017624,27611574,CC BY,"Theiler´s murine encephalomyelitis virus (TMEV)-infection is a widely used animal model for studying demyelinating disorders, including multiple sclerosis (MS). The immunosuppressive cytokine Interleukin (IL)-10 counteracts hyperactive immune responses and critically controls immune homeostasis in infectious and autoimmune disorders. In order to investigate the effect of signaling via Interleukin-10 receptor (IL-10R) in infectious neurological diseases, TMEV-infected SJL mice were treated with IL-10R blocking antibody (Ab) in the acute and chronic phase of the disease. The findings demonstrate that (i) Ab-mediated IL-10 neutralization leads to progressive colitis with a reduction in Foxp3(+) regulatory T cells and increased numbers of CD8(+)CD44(+) memory T cells as well as activated CD4(+)CD69(+) and CD8(+)CD69(+) T cells in uninfected mice. (ii) Concurrent acute TMEV-infection worsened enteric disease-mediated by IL-10R neutralization. Virus-triggered effects were associated with an enhanced activation of CD4(+) T helper cells and CD8(+) cytotoxic T lymphocytes and augmented cytokine expression. By contrast, (iii) IL-10R neutralization during chronic TMEV-infection was not associated with enhanced peripheral immunopathology but an increased CD3(+) T cell influx in the spinal cord. IL-10R neutralization causes a breakdown in peripheral immune tolerance in genetically predisposed mice, which leads to immune-mediated colitis, resembling inflammatory bowel disease. Hyperactive immune state following IL-10R blockade is enhanced by central nervous system-restricted viral infection in a disease phase-dependent manner.",2016 Sep 9,"['Uhde, Ann-Kathrin', 'Herder, Vanessa', 'Akram Khan, Muhammad', 'Ciurkiewicz, Malgorzata', 'Schaudien, Dirk', 'Teich, René', 'Floess, Stefan', 'Baumgärtner, Wolfgang', 'Huehn, Jochen', 'Beineke, Andreas']",PLoS One,,,True
7b7e0cb6554d2f871d6b09daa0b5505472873a20,PMC,Mumps Virus: Modification of the Identify-Isolate-Inform Tool for Frontline Healthcare Providers,http://dx.doi.org/10.5811/westjem.2016.6.30793,PMC5017829,27625709,CC BY,"Mumps is a highly contagious viral infection that became rare in most industrialized countries following the introduction of measles-mumps-rubella (MMR) vaccine in 1967. The disease, however, has been re-emerging with several outbreaks over the past decade. Many clinicians have never seen a case of mumps. To assist frontline healthcare providers with detecting potential cases and initiating critical actions, investigators modified the “Identify-Isolate-Inform” tool for mumps infection. The tool is applicable to regions with rare incidences or local outbreaks, especially seen in college students, as well as globally in areas where vaccination is less common. Mumps begins with a prodrome of low-grade fever, myalgias and malaise/anorexia, followed by development of nonsuppurative parotitis, which is the pathognomonic finding associated with acute mumps infection. Orchitis and meningitis are the two most common serious complications, with hearing loss and infertility occurring rarely. Providers should consider mumps in patients with exposure to a known case or international travel to endemic regions who present with consistent signs and symptoms. If mumps is suspected, healthcare providers must immediately implement standard and droplet precautions and notify the local health department and hospital infection control personnel.",2016 Sep 30,"['Koenig, Kristi L.', 'Shastry, Siri', 'Mzahim, Bandr', 'Almadhyan, Abdulmajeed', 'Burns, Michael J.']",West J Emerg Med,,,True
4aa6c6d082407bee2de3cfdc3a8a11a229904fda,PMC,The multifaceted role of astrocytes in regulating myelination,http://dx.doi.org/10.1016/j.expneurol.2016.03.009,PMC5019113,26988764,CC BY,"Astrocytes are the major glial cell of the central nervous system (CNS), providing both metabolic and physical support to other neural cells. After injury, astrocytes become reactive and express a continuum of phenotypes which may be supportive or inhibitory to CNS repair. This review will focus on the ability of astrocytes to influence myelination in the context of specific secreted factors, cytokines and other neural cell targets within the CNS. In particular, we focus on how astrocytes provide energy and cholesterol to neurons, influence synaptogenesis, affect oligodendrocyte biology and instigate cross-talk between the many cellular components of the CNS.",2016 Sep,"['Kıray, Hülya', 'Lindsay, Susan L.', 'Hosseinzadeh, Sara', 'Barnett, Susan C.']",Exp Neurol,,,False
4d1696e014e57ca335e9fe116840afda273d2ba9,PMC,Etiology and Clinical Characteristics of Single and Multiple Respiratory Virus Infections Diagnosed in Croatian Children in Two Respiratory Seasons,http://dx.doi.org/10.1155/2016/2168780,PMC5021477,27656298,CC BY,"The aim of this study was to determine the causative agent of acute respiratory infection (ARI) in hospitalized children, as well as investigate the characteristics of ARIs with single and multiple virus detection in two respiratory seasons. In 2010 and 2015, nasopharyngeal and pharyngeal swabs from a total of 134 children, admitted to the hospital due to ARI, were tested using multiplex PCR. Viral etiology was established in 81.3% of the patients. Coinfection with two viruses was diagnosed in 27.6% of the patients, and concurrent detection of three or more viruses was diagnosed in 12.8% of the patients. The most commonly diagnosed virus in both seasons combined was respiratory syncytial virus (RSV) (28.6%), followed by parainfluenza viruses (PIVs) types 1–3 (18.4%), rhinovirus (HRV) (14.3%), human metapneumovirus (10.1%), adenovirus (AdV) (7.1%), influenza viruses types A and B (4.8%), and coronaviruses (4.2%). In 2015, additional pathogens were investigated with the following detection rate: enterovirus (13.2%), bocavirus (HBoV) (10.5%), PIV-4 (2.6%), and parechovirus (1.3%). There were no statistical differences between single and multiple virus infection regarding patients age, localization of infection, and severity of disease (P > 0.05). AdV, HRV, HBoV, and PIVs were significantly more often detected in multiple virus infections compared to the other respiratory viruses (P < 0.001).",2016 Aug 30,"['Ljubin-Sternak, Sunčanica', 'Marijan, Tatjana', 'Ivković-Jureković, Irena', 'Čepin-Bogović, Jasna', 'Gagro, Alenka', 'Vraneš, Jasmina']",J Pathog,,,True
12d7a96036ca9e861d3636d55d3841452e455c73,PMC,Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors,http://dx.doi.org/10.1371/journal.pone.0162178,PMC5023107,27627440,CC BY,"We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs). During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant), bacteremia, urinary tract infection (UTI), respiratory virus infection, and varicella zoster virus (VZV) reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant), bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection). Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children.",2016 Sep 14,"['Choi, Young Bae', 'Yi, Eun Sang', 'Kang, Ji-Man', 'Lee, Ji Won', 'Yoo, Keon Hee', 'Kim, Yae-Jean', 'Sung, Ki Woong', 'Koo, Hong Hoe']",PLoS One,,,True
51448d629c1d530b3001bc292c2d819a71ecdf23,PMC,A GeXP-Based Assay for Simultaneous Detection of Multiple Viruses in Hospitalized Children with Community Acquired Pneumonia,http://dx.doi.org/10.1371/journal.pone.0162411,PMC5023126,27627439,CC BY,"The GeXP-based assay has recently been developed for simultaneous detection of multiple pathogens. So far, the application of the GeXP assay to test larger clinical samples has hardly been reported. Community-acquired pneumonia (CAP) is the leading cause of death in children worldwide and a substantial proportion of childhood CAP is caused by viruses. Rapid and accurate diagnosis of virus infection is important for the clinical management of CAP. In this study, we explored the GeXP assay for simultaneous detection of 20 types/subtypes of viruses in hospitalized children with CAP. A total of 1699 nasopharyngeal swabs were prospectively collected and viral nucleic acid was extracted and assayed. Using viral genomic DNA or RNA as template, we showed that at the concentration of 10(4) copies of DNA or RNA of each virus/μl, all 20 target viruses were simultaneously identified by the GeXP assay. Fifteen control microorganisms, in contrast, failed to be amplified by the assay. About 65% of cases tested in this study had viral infection, with patients aged <3 years having a 70% positive rate, significantly higher than that in patients aged > 3 years (40%). The most frequently detected virus was RSV followed by PIV3, HRV, ADV and HBoV. Seasonal distribution analysis revealed that RSV was the most predominant in autumn and winter, while in spring and summer PIV3 and RSV were the most frequently identified with similar positive percentages. One hundred twenty randomly-chosen samples tested by the GeXP assay were re-evaluated by mono-RT-PCR, the results showed 97.5% diagnosis agreement between these 2 methods. Our findings suggest that the GeXP assay could be a valuable diagnostic tool for virus infection in pediatric patients with CAP.",2016 Sep 14,"['Wang, Le', 'Zhao, Mengchuan', 'Shi, Zhongren', 'Feng, Zhishan', 'Guo, Weiwei', 'Yang, Shuo', 'Liu, Lanping', 'Li, Guixia']",PLoS One,,,True
1a29f97fc037ea6456b41d054e5603fbd4f76e94,PMC,Presence of Vaccine-Derived Newcastle Disease Viruses in Wild Birds,http://dx.doi.org/10.1371/journal.pone.0162484,PMC5023329,27626272,CC0,"Our study demonstrates the repeated isolation of vaccine-derived Newcastle disease viruses from different species of wild birds across four continents from 1997 through 2014. The data indicate that at least 17 species from ten avian orders occupying different habitats excrete vaccine-derived Newcastle disease viruses. The most frequently reported isolates were detected among individuals in the order Columbiformes (n = 23), followed in frequency by the order Anseriformes (n = 13). Samples were isolated from both free-ranging (n = 47) and wild birds kept in captivity (n = 7). The number of recovered vaccine-derived viruses corresponded with the most widely utilized vaccines, LaSota (n = 28) and Hitchner B1 (n = 19). Other detected vaccine-derived viruses resembled the PHY-LMV2 and V4 vaccines, with five and two cases, respectively. These results and the ubiquitous and synanthropic nature of wild pigeons highlight their potential role as indicator species for the presence of Newcastle disease virus of low virulence in the environment. The reverse spillover of live agents from domestic animals to wildlife as a result of the expansion of livestock industries employing massive amounts of live virus vaccines represent an underappreciated and poorly studied effect of human activity on wildlife.",2016 Sep 14,"['Ayala, Andrea J.', 'Dimitrov, Kiril M.', 'Becker, Cassidy R.', 'Goraichuk, Iryna V.', 'Arns, Clarice W.', 'Bolotin, Vitaly I.', 'Ferreira, Helena L.', 'Gerilovych, Anton P.', 'Goujgoulova, Gabriela V.', 'Martini, Matheus C.', 'Muzyka, Denys V.', 'Orsi, Maria A.', 'Scagion, Guilherme P.', 'Silva, Renata K.', 'Solodiankin, Olexii S.', 'Stegniy, Boris T.', 'Miller, Patti J.', 'Afonso, Claudio L.']",PLoS One,,,True
acb8ae819eaf658a9e9704220f1e987a0365675e,PMC,Monocytes and B cells support active replication of Chandipura virus,http://dx.doi.org/10.1186/s12879-016-1794-6,PMC5024506,27628855,CC BY,"BACKGROUND: Interaction between immune system and Chandipura virus (CHPV) during different stages of its life cycle remain poorly understood. The exact route of virus entry into the blood and CNS invasion has not been clearly defined. The present study was undertaken to assess the population in PBMC that supports the growth of virus and to detect active virus replication in PBMC as well as its subsets. METHODS: PBMC subsets viz.: CD3(+), CD14(+), CD19(+), CD56(+)cells were separated and infected with CHPV. The infected cells were then assessed for transcription (N gene primer) and replication (NP gene primer) of CHPV by PCR. The supernatant collected from infected cells were titrated in Baby Hamster Kidney (BHK) cells to assess virus release. The cytokine and chemokine expression was quantified by flow cytometry. RESULTS: Amplification of N and NP gene was detected in CD14(+) (monocyte) and CD19(+) (B cell), significant increase in virus titre was also observed in these subsets. It was observed that, although the levels of IL-6 and IL-10 were elevated in CD14(+) cells as compared to CD19(+)cells, the differences were not significant. However the levels of TNFα and IL-8 were significantly elevated in CD14(+) cells than in CD19(+)cells. The levels of chemokine (CXCL9, CCL5, CCL2, CXCL10) were significantly elevated in CHPV infected PBMC as compared to uninfected cells. CCL2 and CXCL9 were significantly increased in CHPV infected CD14(+)cells as compared to CD19(+) cells. CONCLUSION: CD14(+)and CD19(+)cells support active replication of CHPV. High viral load was detected in CD14(+) cells infected with CHPV hence it might be the primary target cells for active replication of CHPV. An elevated levels of cytokines and chemokines observed in CD14(+) cells may help in predicting the pathogenecity of CHPV and possible entry into the central nervous system.",2016 Sep 14,"['Roy, Soumen', 'Pavitrakar, Daya', 'Gunjikar, Rashmi', 'Ayachit, Vijay M.', 'Bondre, Vijay P.', 'Sapkal, Gajanan N.']",BMC Infect Dis,,,True
132d356a5461491379ccfb628fca604ef66b53e2,PMC,Influenza B virus non-structural protein 1 counteracts ISG15 antiviral activity by sequestering ISGylated viral proteins,http://dx.doi.org/10.1038/ncomms12754,PMC5025834,27587337,CC BY,"The ubiquitin-like protein ISG15 and its conjugation to proteins (ISGylation) are strongly induced by type I interferon. Influenza B virus encodes non-structural protein 1 (NS1B) that binds human ISG15 and provides an appropriate model for determining how ISGylation affects virus replication in human cells. Here using a recombinant virus encoding a NS1B protein defective in ISG15 binding, we show that NS1B counteracts ISGylation-mediated antiviral activity by binding and sequestering ISGylated viral proteins, primarily ISGylated viral nucleoprotein (NP), in infected cells. ISGylated NP that is not sequestered by mutant NS1B acts as a dominant-negative inhibitor of oligomerization of the more abundant unconjugated NP. Consequently formation of viral ribonucleoproteins that catalyse viral RNA synthesis is inhibited, causing decreased viral protein synthesis and virus replication. We verify that ISGylated NP is largely responsible for inhibition of viral RNA synthesis by generating recombinant viruses that lack known ISGylation sites in NP.",2016 Sep 2,"['Zhao, Chen', 'Sridharan, Haripriya', 'Chen, Ran', 'Baker, Darren P.', 'Wang, Shanshan', 'Krug, Robert M.']",Nat Commun,,,True
53fa60a93898a5901b87fe8ad651ac5f75611071,PMC,Influenza B virus non-structural protein 1 counteracts ISG15 antiviral activity by sequestering ISGylated viral proteins,http://dx.doi.org/10.1038/ncomms12754,PMC5025834,27587337,CC BY,"The ubiquitin-like protein ISG15 and its conjugation to proteins (ISGylation) are strongly induced by type I interferon. Influenza B virus encodes non-structural protein 1 (NS1B) that binds human ISG15 and provides an appropriate model for determining how ISGylation affects virus replication in human cells. Here using a recombinant virus encoding a NS1B protein defective in ISG15 binding, we show that NS1B counteracts ISGylation-mediated antiviral activity by binding and sequestering ISGylated viral proteins, primarily ISGylated viral nucleoprotein (NP), in infected cells. ISGylated NP that is not sequestered by mutant NS1B acts as a dominant-negative inhibitor of oligomerization of the more abundant unconjugated NP. Consequently formation of viral ribonucleoproteins that catalyse viral RNA synthesis is inhibited, causing decreased viral protein synthesis and virus replication. We verify that ISGylated NP is largely responsible for inhibition of viral RNA synthesis by generating recombinant viruses that lack known ISGylation sites in NP.",2016 Sep 2,"['Zhao, Chen', 'Sridharan, Haripriya', 'Chen, Ran', 'Baker, Darren P.', 'Wang, Shanshan', 'Krug, Robert M.']",Nat Commun,,,True
3256ad6795fb323a3711f3d3d6f7ae85657fc5ff,PMC,Biochemical and structural characterization of the interface mediating interaction between the influenza A virus non-structural protein-1 and a monoclonal antibody,http://dx.doi.org/10.1038/srep33382,PMC5025888,27633136,CC BY,"We have previously shown that a non-structural protein 1 (NS1)-binding monoclonal antibody, termed as 2H6, can significantly reduce influenza A virus (IAV) replication when expressed intracellularly. In this study, we further showed that 2H6 binds stronger to the NS1 of H5N1 than A/Puerto Rico/8/1934(H1N1) because of an amino acid difference at residue 48. A crystal structure of 2H6 fragment antigen-binding (Fab) has also been solved and docked onto the NS1 structure to reveal the contacts between specific residues at the interface of antibody-antigen complex. In one of the models, the predicted molecular contacts between residues in NS1 and 2H6-Fab correlate well with biochemical results. Taken together, residues N48 and T49 in H5N1 NS1 act cooperatively to maintain a strong interaction with mAb 2H6 by forming hydrogen bonds with residues found in the heavy chain of the antibody. Interestingly, the pandemic H1N1-2009 and the majority of seasonal H3N2 circulating in humans since 1968 has N48 in NS1, suggesting that mAb 2H6 could bind to most of the currently circulating seasonal influenza A virus strains. Consistent with the involvement of residue T49, which is well-conserved, in RNA binding, mAb 2H6 was also found to inhibit the interaction between NS1 and double-stranded RNA.",2016 Sep 16,"['Wu, Jianping', 'Mok, Chee-Keng', 'Chow, Vincent Tak Kwong', 'Yuan, Y. Adam', 'Tan, Yee-Joo']",Sci Rep,,,True
4468cfd09ed3ad64822cc4fc843b2bea5684cc46,PMC,Biochemical and structural characterization of the interface mediating interaction between the influenza A virus non-structural protein-1 and a monoclonal antibody,http://dx.doi.org/10.1038/srep33382,PMC5025888,27633136,CC BY,"We have previously shown that a non-structural protein 1 (NS1)-binding monoclonal antibody, termed as 2H6, can significantly reduce influenza A virus (IAV) replication when expressed intracellularly. In this study, we further showed that 2H6 binds stronger to the NS1 of H5N1 than A/Puerto Rico/8/1934(H1N1) because of an amino acid difference at residue 48. A crystal structure of 2H6 fragment antigen-binding (Fab) has also been solved and docked onto the NS1 structure to reveal the contacts between specific residues at the interface of antibody-antigen complex. In one of the models, the predicted molecular contacts between residues in NS1 and 2H6-Fab correlate well with biochemical results. Taken together, residues N48 and T49 in H5N1 NS1 act cooperatively to maintain a strong interaction with mAb 2H6 by forming hydrogen bonds with residues found in the heavy chain of the antibody. Interestingly, the pandemic H1N1-2009 and the majority of seasonal H3N2 circulating in humans since 1968 has N48 in NS1, suggesting that mAb 2H6 could bind to most of the currently circulating seasonal influenza A virus strains. Consistent with the involvement of residue T49, which is well-conserved, in RNA binding, mAb 2H6 was also found to inhibit the interaction between NS1 and double-stranded RNA.",2016 Sep 16,"['Wu, Jianping', 'Mok, Chee-Keng', 'Chow, Vincent Tak Kwong', 'Yuan, Y. Adam', 'Tan, Yee-Joo']",Sci Rep,,,False
d0d47cee33a4e690e05f6277dd513682b7d35bdb,PMC,Immunogenicity of RSV F DNA Vaccine in BALB/c Mice,http://dx.doi.org/10.1155/2016/7971847,PMC5027326,27688769,CC BY,"Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease leading to numerous hospitalizations and deaths among the infant and elderly populations worldwide. There is no vaccine or a less effective drug available against RSV infections. Natural RSV infection stimulates the Th1 immune response and activates the production of neutralizing antibodies, while earlier vaccine trials that used UV-inactivated RSV exacerbated the disease due to the activation of the allergic Th2 response. With a focus on Th1 immunity, we developed a DNA vaccine containing the native RSV fusion (RSV F) protein and studied its immune response in BALB/c mice. High levels of RSV specific antibodies were induced during subsequent immunizations. The serum antibodies were able to neutralize RSV in vitro. The RSV inhibition by sera was also shown by immunofluorescence analyses. Antibody response of the RSV F DNA vaccine showed a strong Th1 response. Also, sera from RSV F immunized and RSV infected mice reduced the RSV infection by 50% and 80%, respectively. Our data evidently showed that the RSV F DNA vaccine activated the Th1 biased immune response and led to the production of neutralizing antibodies, which is the desired immune response required for protection from RSV infections.",2016 Sep 5,"['Eroglu, Erdal', 'Singh, Ankur', 'Bawage, Swapnil', 'Tiwari, Pooja M.', 'Vig, Komal', 'Pillai, Shreekumar R.', 'Dennis, Vida A.', 'Singh, Shree R.']",Adv Virol,,,True
0022796bb2112abd2e6423ba2d57751db06049fb,PMC,Public Health Responses to and Challenges for the Control of Dengue Transmission in High-Income Countries: Four Case Studies,http://dx.doi.org/10.1371/journal.pntd.0004943,PMC5028037,27643596,CC BY,"Dengue has a negative impact in low- and lower middle-income countries, but also affects upper middle- and high-income countries. Despite the efforts at controlling this disease, it is unclear why dengue remains an issue in affluent countries. A better understanding of dengue epidemiology and its burden, and those of chikungunya virus and Zika virus which share vectors with dengue, is required to prevent the emergence of these diseases in high-income countries in the future. The purpose of this review was to assess the relative burden of dengue in four high-income countries and to appraise the similarities and differences in dengue transmission. We searched PubMed, ISI Web of Science, and Google Scholar using specific keywords for articles published up to 05 May 2016. We found that outbreaks rarely occur where only Aedes albopictus is present. The main similarities between countries uncovered by our review are the proximity to dengue-endemic countries, the presence of a competent mosquito vector, a largely nonimmune population, and a lack of citizens’ engagement in control of mosquito breeding. We identified important epidemiological and environmental issues including the increase of local transmission despite control efforts, population growth, difficulty locating larval sites, and increased human mobility from neighboring endemic countries. Budget cuts in health and lack of practical vaccines contribute to an increased risk. To be successful, dengue-control programs for high-income countries must consider the epidemiology of dengue in other countries and use this information to minimize virus importation, improve the control of the cryptic larval habitat, and engage the community in reducing vector breeding. Finally, the presence of a communicable disease center is critical for managing and reducing future disease risks.",2016 Sep 19,"['Viennet, Elvina', 'Ritchie, Scott A.', 'Williams, Craig R.', 'Faddy, Helen M.', 'Harley, David']",PLoS Negl Trop Dis,,,True
8b71af2afcb6a76e746d1a9d77d018d28efd4969,PMC,Transcriptomic Analysis of Persistent Infection with Foot-and-Mouth Disease Virus in Cattle Suggests Impairment of Apoptosis and Cell-Mediated Immunity in the Nasopharynx,http://dx.doi.org/10.1371/journal.pone.0162750,PMC5028045,27643611,CC0,"In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vaccine, 10 non-vaccinated) were challenged with FMDV A(24) Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carriers were further compared to 2 naïve animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and a minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467) had higher expression in carriers. Among these, genes associated with cellular proliferation and the immune response–such as chemokines, cytokines and genes regulating T and B cells–were significantly overrepresented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97), indicating a similar transcriptome profile across these groups. Genes related to prostaglandin E(2) production and the induction of regulatory T cells were overexpressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance. Based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatory T cells.",2016 Sep 19,"['Eschbaumer, Michael', 'Stenfeldt, Carolina', 'Smoliga, George R.', 'Pacheco, Juan M.', 'Rodriguez, Luis L.', 'Li, Robert W.', 'Zhu, James', 'Arzt, Jonathan']",PLoS One,,,True
73068e027281777c2e06dfc12d03b082b46e9536,PMC,Transcriptomic Analysis of Persistent Infection with Foot-and-Mouth Disease Virus in Cattle Suggests Impairment of Apoptosis and Cell-Mediated Immunity in the Nasopharynx,http://dx.doi.org/10.1371/journal.pone.0162750,PMC5028045,27643611,CC0,"In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vaccine, 10 non-vaccinated) were challenged with FMDV A(24) Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carriers were further compared to 2 naïve animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and a minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467) had higher expression in carriers. Among these, genes associated with cellular proliferation and the immune response–such as chemokines, cytokines and genes regulating T and B cells–were significantly overrepresented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97), indicating a similar transcriptome profile across these groups. Genes related to prostaglandin E(2) production and the induction of regulatory T cells were overexpressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance. Based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatory T cells.",2016 Sep 19,"['Eschbaumer, Michael', 'Stenfeldt, Carolina', 'Smoliga, George R.', 'Pacheco, Juan M.', 'Rodriguez, Luis L.', 'Li, Robert W.', 'Zhu, James', 'Arzt, Jonathan']",PLoS One,,,False
933bde921b806a7157fe084a0256ed26d394e8cd,PMC,Transcriptomic Analysis of Persistent Infection with Foot-and-Mouth Disease Virus in Cattle Suggests Impairment of Apoptosis and Cell-Mediated Immunity in the Nasopharynx,http://dx.doi.org/10.1371/journal.pone.0162750,PMC5028045,27643611,CC0,"In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vaccine, 10 non-vaccinated) were challenged with FMDV A(24) Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carriers were further compared to 2 naïve animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and a minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467) had higher expression in carriers. Among these, genes associated with cellular proliferation and the immune response–such as chemokines, cytokines and genes regulating T and B cells–were significantly overrepresented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97), indicating a similar transcriptome profile across these groups. Genes related to prostaglandin E(2) production and the induction of regulatory T cells were overexpressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance. Based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatory T cells.",2016 Sep 19,"['Eschbaumer, Michael', 'Stenfeldt, Carolina', 'Smoliga, George R.', 'Pacheco, Juan M.', 'Rodriguez, Luis L.', 'Li, Robert W.', 'Zhu, James', 'Arzt, Jonathan']",PLoS One,,,False
d096bbd29d25374aa7fea667ac750e5739370dcf,PMC,A systematic view on influenza induced host shutoff,http://dx.doi.org/10.7554/eLife.18311,PMC5028189,27525483,CC BY,"Host shutoff is a common strategy used by viruses to repress cellular mRNA translation and concomitantly allow the efficient translation of viral mRNAs. Here we use RNA-sequencing and ribosome profiling to explore the mechanisms that are being utilized by the Influenza A virus (IAV) to induce host shutoff. We show that viral transcripts are not preferentially translated and instead the decline in cellular protein synthesis is mediated by viral takeover on the mRNA pool. Our measurements also uncover strong variability in the levels of cellular transcripts reduction, revealing that short transcripts are less affected by IAV. Interestingly, these mRNAs that are refractory to IAV infection are enriched in cell maintenance processes such as oxidative phosphorylation. Furthermore, we show that the continuous oxidative phosphorylation activity is important for viral propagation. Our results advance our understanding of IAV-induced shutoff, and suggest a mechanism that facilitates the translation of genes with important housekeeping functions. DOI: http://dx.doi.org/10.7554/eLife.18311.001",,"['Bercovich-Kinori, Adi', 'Tai, Julie', 'Gelbart, Idit Anna', 'Shitrit, Alina', 'Ben-Moshe, Shani', 'Drori, Yaron', 'Itzkovitz, Shalev', 'Mandelboim, Michal', 'Stern-Ginossar, Noam']",eLife.; 5:e18311,,,True
96a1e9e95b2ab796897177f18a1d3e148b83e57e,PMC,The evidence of porcine hemagglutinating encephalomyelitis virus induced nonsuppurative encephalitis as the cause of death in piglets,http://dx.doi.org/10.7717/peerj.2443,PMC5028786,27672502,CC BY,"An acute outbreak of porcine hemagglutinating encephalomyelitis virus (PHEV) infection in piglets, characterized with neurological symptoms, vomiting, diarrhea, and wasting, occurred in China. Coronavirus-like particles were observed in the homogenized tissue suspensions of the brain of dead piglets by electron microscopy, and a wild PHEV strain was isolated, characterized, and designated as PHEV-CC14. Histopathologic examinations of the dead piglets showed characteristics of non-suppurative encephalitis, and some neurons in the cerebral cortex were degenerated and necrotic, and neuronophagia. Similarly, mice inoculated with PHEV-CC14 were found to have central nervous system (CNS) dysfunction, with symptoms of depression, arched waists, standing and vellicating front claws. Furthmore, PHEV-positive labeling of neurons in cortices of dead piglets and infected mice supported the viral infections of the nervous system. Then, the major structural genes of PHEV-CC14 were sequenced and phylogenetically analyzed, and the strain shared 95%–99.2% nt identity with the other PHEV strains available in GenBank. Phylogenetic analysis clearly proved that the wild strain clustered into a subclass with a HEV-JT06 strain. These findings suggested that the virus had a strong tropism for CNS, in this way, inducing nonsuppurative encephalitis as the cause of death in piglets. Simultaneously, the predicted risk of widespread transmission showed a certain variation among the PHEV strains currently circulating around the world. Above all, the information presented in this study can not only provide good reference for the experimental diagnosis of PHEV infection for pig breeding, but also promote its new effective vaccine development.",2016 Sep 15,"['Li, Zi', 'He, Wenqi', 'Lan, Yungang', 'Zhao, Kui', 'Lv, Xiaoling', 'Lu, Huijun', 'Ding, Ning', 'Zhang, Jing', 'Shi, Junchao', 'Shan, Changjian', 'Gao, Feng']",PeerJ,,,True
6d1b4e1200c1da4dff5048bdff36805e28511154,PMC,Cats are not small dogs: is there an immunological explanation for why cats are less affected by arthropod-borne disease than dogs?,http://dx.doi.org/10.1186/s13071-016-1798-5,PMC5028948,27646278,CC BY,"It is widely recognized that cats appear to be less frequently affected by arthropod-borne infectious diseases than dogs and share fewer zoonotic pathogens with man. This impression is supported by the relative lack of scientific publications related to feline vector-borne infections. This review explores the possible reasons for the difference between the two most common small companion animal species, including the hypothesis that cats might have a genetically-determined immunological resistance to arthropod vectors or the microparasites they transmit. A number of simple possibilities might account for the lower prevalence of these diseases in cats, including factors related to the lifestyle and behaviour of the cat, lesser spend on preventative healthcare for cats and reduced opportunities for research funding for these animals. The dog and cat have substantially similar immune system components, but differences in immune function might in part account for the markedly distinct prevalence and clinicopathological appearance of autoimmune, allergic, idiopathic inflammatory, immunodeficiency, neoplastic and infectious diseases in the two species. Cats have greater genetic diversity than dogs with much lower linkage disequilibrium in feline compared with canine breed groups. Immune function is intrinsically related to the nature of the intestinal microbiome and subtle differences between the canine and feline microbial populations might also impact on immune function and disease resistance. The reasons for the apparent lesser susceptibility of cats to arthropod-borne infectious diseases are likely to be complex, but warrant further investigation.",2016 Sep 20,"Day, Michael J.",Parasit Vectors,,,True
9574215db9b33b5a09628c58401bb06f0433e5c8,PMC,Changes in serum proteins after endotoxin administration in healthy and choline-treated calves,http://dx.doi.org/10.1186/s12917-016-0837-y,PMC5028968,27646125,CC BY,"BACKGROUND: This study aimed to investigate the possible serum protein changes after endotoxin administration in healthy and choline-treated calves using proteomics. These results are expected to contribute to the understanding of the pathophysiological mechanisms of endotoxemia and the beneficial effect of choline administration in this clinical situation. METHODS: Healthy-calves (n = 20) were divided into 4 groups: Control, Choline treated (C), Lipopolysaccharide administered (LPS), and LPS + C. Control calves received 0.9 % NaCl injection. Calves in C and LPS + C groups received choline chloride (1 mg/kg/iv). Endotoxin (LPS) was injected (2 μg/kg/iv) to the calves in LPS and LPS + C groups. Serum samples were collected before and after the treatments. Differentially expressed proteins (> 1.5 fold-change relative to controls) were identified by LC-MS/MS. RESULTS: After LPS administration, 14 proteins increased, and 13 proteins decreased within 48 h as compared to controls. In the LPS group, there were significant increases in serum levels of ragulator complex protein (189-fold) and galectin-3-binding protein (10-fold), but transcription factor MafF and corticosteroid binding globulin were down regulated (≥ 5 fold). As compared with the LPS group, in LPS + C group, fibrinogen gamma-B-chain and antithrombin were up-regulated, while hemopexin and histone H4 were down-regulated. Choline treatment attenuated actin alpha cardiac muscle-1 overexpression after LPS. CONCLUSIONS: LPS administration produces changes in serum proteins associated with lipid metabolism, immune and inflammatory response, protein binding/transport, cell adhesion, venous thrombosis, cardiac contractility and blood coagulation. The administration of choline is associated with changes in proteins which can be related with its beneficial effect in this clinical situation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0837-y) contains supplementary material, which is available to authorized users.",2016 Sep 20,"['Yilmaz, Z.', 'Eralp Inan, O.', 'Kocaturk, M.', 'Baykal, A. T.', 'Hacariz, O.', 'Hatipoglu, I.', 'Tvarijonaviciute, A.', 'Cansev, M.', 'Ceron, J.', 'Ulus, I. H.']",BMC Vet Res,,,True
37f723594fc45504f7f8d4fc7ca0190513a639c0,PMC,Expansion and Functional Divergence of AP2 Group Genes in Spermatophytes Determined by Molecular Evolution and Arabidopsis Mutant Analysis,http://dx.doi.org/10.3389/fpls.2016.01383,PMC5029118,27703459,CC BY,"The APETALA2 (AP2) genes represent the AP2 group within a large group of DNA-binding proteins called AP2/EREBP. The AP2 gene is functional and necessary for flower development, stem cell maintenance, and seed development, whereas the other members of AP2 group redundantly affect flowering time. Here we study the phylogeny of AP2 group genes in spermatophytes. Spermatophyte AP2 group genes can be classified into AP2 and TOE types, six clades, and we found that the AP2 group homologs in gymnosperms belong to the AP2 type, whereas TOE types are absent, which indicates the AP2 type gene are more ancient and TOE type was split out of AP2 type and losing the major function. In Brassicaceae, the expansion of AP2 and TOE type lead to the gene number of AP2 group were up to six. Purifying selection appears to have been the primary driving force of spermatophyte AP2 group evolution, although positive selection occurred in the AP2 clade. The transition from exon to intron of AtAP2 in Arabidopsis mutant leads to the loss of gene function and the same situation was found in AtTOE2. Combining this evolutionary analysis and published research, the results suggest that typical AP2 group genes may first appear in gymnosperms and diverged in angiosperms, following expansion of group members and functional differentiation. In angiosperms, AP2 genes (AP2 clade) inherited key functions from ancestors and other genes of AP2 group lost most function but just remained flowering time controlling in gene formation. In this study, the phylogenies of AP2 group genes in spermatophytes was analyzed, which supported the evidence for the research of gene functional evolution of AP2 group.",2016 Sep 20,"['Wang, Pengkai', 'Cheng, Tielong', 'Lu, Mengzhu', 'Liu, Guangxin', 'Li, Meiping', 'Shi, Jisen', 'Lu, Ye', 'Laux, Thomas', 'Chen, Jinhui']",Front Plant Sci,,,True
376ac2d5c7446918fdc12ef89696687b8a2b23d8,PMC,Differential Regulation of Self-reactive CD4(+) T Cells in Cervical Lymph Nodes and Central Nervous System during Viral Encephalomyelitis,http://dx.doi.org/10.3389/fimmu.2016.00370,PMC5030268,27708643,CC BY,"Viral infections have long been implicated as triggers of autoimmune diseases, including multiple sclerosis (MS), a central nervous system (CNS) inflammatory demyelinating disorder. Epitope spreading, molecular mimicry, cryptic antigen, and bystander activation have been implicated as mechanisms responsible for activating self-reactive (SR) immune cells, ultimately leading to organ-specific autoimmune disease. Taking advantage of coronavirus JHM strain of mouse hepatitis virus (JHMV)-induced demyelination, this study demonstrates that the host also mounts counteractive measures to specifically limit expansion of endogenous SR T cells. In this model, immune-mediated demyelination is associated with induction of SR T cells after viral control. However, their decline during persisting infection, despite ongoing demyelination, suggests an active control mechanism. Antigen-specific IL-10-secreting CD4(+) T cells (Tr1) and Foxp3(+) regulatory T cells (Tregs), both known to control autoimmunity and induced following JHMV infection, were assessed for their relative in vivo suppressive function of SR T cells. Ablation of Foxp3(+) Tregs in chronically infected DEREG mice significantly increased SR CD4(+) T cells within cervical lymph nodes (CLN), albeit without affecting their numbers or activation within the CNS compared to controls. In contrast, infected IL-27 receptor deficient (IL-27R(−/−)) mice, characterized by a drastic reduction of Tr1 cells, revealed that SR CD4(+) T cells in CLN remained unchanged but were specifically increased within the CNS. These results suggest that distinct Treg subsets limit SR T cells in the draining lymph nodes and CNS to maximize suppression of SR T-cell-mediated autoimmune pathology. The JHMV model is thus valuable to decipher tissue-specific mechanisms preventing autoimmunity.",2016 Sep 21,"['Savarin, Carine', 'Bergmann, Cornelia C.', 'Hinton, David R.', 'Stohlman, Stephen A.']",Front Immunol,,,True
69d3400351b1b4dbce54ecdec3d4c897dc76b9a8,PMC,Tuberculosis Susceptibility and Vaccine Protection Are Independently Controlled by Host Genotype,http://dx.doi.org/10.1128/mBio.01516-16,PMC5030360,27651361,CC BY,"The outcome of Mycobacterium tuberculosis infection and the immunological response to the bacillus Calmette-Guerin (BCG) vaccine are highly variable in humans. Deciphering the relative importance of host genetics, environment, and vaccine preparation for the efficacy of BCG has proven difficult in natural populations. We developed a model system that captures the breadth of immunological responses observed in outbred individual mice, which can be used to understand the contribution of host genetics to vaccine efficacy. This system employs a panel of highly diverse inbred mouse strains, consisting of the founders and recombinant progeny of the “Collaborative Cross” project. Unlike natural populations, the structure of this panel allows the serial evaluation of genetically identical individuals and the quantification of genotype-specific effects of interventions such as vaccination. When analyzed in the aggregate, our panel resembled natural populations in several important respects: the animals displayed a broad range of susceptibility to M. tuberculosis, differed in their immunological responses to infection, and were not durably protected by BCG vaccination. However, when analyzed at the genotype level, we found that these phenotypic differences were heritable. M. tuberculosis susceptibility varied between lines, from extreme sensitivity to progressive M. tuberculosis clearance. Similarly, only a minority of the genotypes was protected by vaccination. The efficacy of BCG was genetically separable from susceptibility to M. tuberculosis, and the lack of efficacy in the aggregate analysis was driven by nonresponsive lines that mounted a qualitatively distinct response to infection. These observations support an important role for host genetic diversity in determining BCG efficacy and provide a new resource to rationally develop more broadly efficacious vaccines.",2016 Sep 20,"['Smith, Clare M.', 'Proulx, Megan K.', 'Olive, Andrew J.', 'Laddy, Dominick', 'Mishra, Bibhuti B.', 'Moss, Caitlin', 'Gutierrez, Nuria Martinez', 'Bellerose, Michelle M.', 'Barreira-Silva, Palmira', 'Phuah, Jia Yao', 'Baker, Richard E.', 'Behar, Samuel M.', 'Kornfeld, Hardy', 'Evans, Thomas G.', 'Beamer, Gillian', 'Sassetti, Christopher M.']",mBio,,,True
044e273c24dbb1ec49d20e760568a100efffab20,PMC,Tuberculosis Susceptibility and Vaccine Protection Are Independently Controlled by Host Genotype,http://dx.doi.org/10.1128/mBio.01516-16,PMC5030360,27651361,CC BY,"The outcome of Mycobacterium tuberculosis infection and the immunological response to the bacillus Calmette-Guerin (BCG) vaccine are highly variable in humans. Deciphering the relative importance of host genetics, environment, and vaccine preparation for the efficacy of BCG has proven difficult in natural populations. We developed a model system that captures the breadth of immunological responses observed in outbred individual mice, which can be used to understand the contribution of host genetics to vaccine efficacy. This system employs a panel of highly diverse inbred mouse strains, consisting of the founders and recombinant progeny of the “Collaborative Cross” project. Unlike natural populations, the structure of this panel allows the serial evaluation of genetically identical individuals and the quantification of genotype-specific effects of interventions such as vaccination. When analyzed in the aggregate, our panel resembled natural populations in several important respects: the animals displayed a broad range of susceptibility to M. tuberculosis, differed in their immunological responses to infection, and were not durably protected by BCG vaccination. However, when analyzed at the genotype level, we found that these phenotypic differences were heritable. M. tuberculosis susceptibility varied between lines, from extreme sensitivity to progressive M. tuberculosis clearance. Similarly, only a minority of the genotypes was protected by vaccination. The efficacy of BCG was genetically separable from susceptibility to M. tuberculosis, and the lack of efficacy in the aggregate analysis was driven by nonresponsive lines that mounted a qualitatively distinct response to infection. These observations support an important role for host genetic diversity in determining BCG efficacy and provide a new resource to rationally develop more broadly efficacious vaccines.",2016 Sep 20,"['Smith, Clare M.', 'Proulx, Megan K.', 'Olive, Andrew J.', 'Laddy, Dominick', 'Mishra, Bibhuti B.', 'Moss, Caitlin', 'Gutierrez, Nuria Martinez', 'Bellerose, Michelle M.', 'Barreira-Silva, Palmira', 'Phuah, Jia Yao', 'Baker, Richard E.', 'Behar, Samuel M.', 'Kornfeld, Hardy', 'Evans, Thomas G.', 'Beamer, Gillian', 'Sassetti, Christopher M.']",mBio,,,False
a2f961fd82a92373256efd31318904eaa6cf6c64,PMC,Prediction and In Silico Identification of Novel B-Cells and T-Cells Epitopes in the S1-Spike Glycoprotein of M41 and CR88 (793/B) Infectious Bronchitis Virus Serotypes for Application in Peptide Vaccines,http://dx.doi.org/10.1155/2016/5484972,PMC5030393,27667997,CC BY,"Bioinformatic analysis was used to predict antigenic B-cell and T-cell epitopes within the S1 glycoprotein of M41 and CR88 IBV strains. A conserved linear B-cell epitope peptide, YTSNETTDVTS(175–185), was identified in M41 IBV strains while three such epitopes types namely, VSNASPNSGGVD(279–290), HPKCNFRPENI(328–338), and NETNNAGSVSDCTAGT(54–69), were predicted in CR88 IBV strains. Analysis of MHCI binding peptides in M41 IBV strains revealed the presence of 15 antigenic peptides out of which 12 were highly conserved in 96–100% of the total M41 strains analysed. Interestingly three of these peptides, GGPITYKVM(208), WFNSLSVSI(356), and YLADAGLAI(472), relatively had high antigenicity index (>1.0). On the other hand, 11 MHCI binding epitope peptides were identified in CR88 IBV strains. Of these, five peptides were found to be highly conserved with a range between 90% and 97%. However, WFNSLSVSL(358), SYNISAASV(88), and YNISAASVA(89) peptides comparably showed high antigenicity scores (>1.0). Combination of antigenic B-cells and T-cells peptides that are conserved across many strains as approach to evoke humoral and CTL immune response will potentially lead to a broad-based vaccine that could reduce the challenges in using live attenuated vaccine technology in the control of IBV infection in poultry.",2016 Sep 7,"['Bande, Faruku', 'Arshad, Siti Suri', 'Hair Bejo, Mohd', 'Kadkhodaei, Saeid', 'Omar, Abdul Rahman']",Adv Bioinformatics,,,True
f5ff89ebfdd0375d034c112c6c1c7e163fa69a0c,PMC,"Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in Réunion Island, 2011-2012",http://dx.doi.org/10.1371/journal.pone.0163377,PMC5031398,27654509,CC BY,"In Réunion Island, despite an influenza surveillance established since 1996 by the sentinel general practitioner’s network, little is known about the etiology of Influenza like-illness (ILI) that differs from influenza viruses in a tropical area. We set up a retrospective study using nasal swabs collected by sentinel GPs from ILI patients in 2011 and 2012. A total of 250 swabs were randomly selected and analyzed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) including research of 18 viruses and 4 bacteria. We detected respiratory viruses in 169/222 (76.1%) samples, mostly rhinovirus (23.4%), influenza A virus (21.2%), influenza B virus (12.6%), coronavirus (4.9%) and Human metapneumovirus (3.6%). Nine swabs (5.3% of positive swabs) revealed co-infections with two viruses identified, among which six concerned co-infections with influenza viruses. We observed important seasonal differences, with circulation of Human Metapneumoviruses, RSV A and B and coronavirus only during summer; whereas parainfluenza viruses were identified only during winter. In conclusion, this study highlights a substantial circulation of multiple respiratory pathogens in Réunion Island throughout the year. It shows that ILI are not only attributable to influenza and underlines the need for biological surveillance. As the use of multiplex RT-PCR showed its efficacy, it is now used routinely in the surveillance of ILI.",2016 Sep 21,"['Brottet, Elise', 'Jaffar-Bandjee, Marie-Christine', 'Li-Pat-Yuen, Ghislaine', 'Filleul, Laurent']",PLoS One,,,True
b11cf879da2036d92fbdbbca07fd8cb7f0416e5f,PMC,A Rationally Designed TNF-α Epitope-Scaffold Immunogen Induces Sustained Antibody Response and Alleviates Collagen-Induced Arthritis in Mice,http://dx.doi.org/10.1371/journal.pone.0163080,PMC5033357,27658047,CC BY,"The TNF-α biological inhibitors have significantly improved the clinical outcomes of many autoimmune diseases, in particular rheumatoid arthritis. However, the practical uses are limited due to high costs and the risk of anti-drug antibody responses. Attempts to develop anti-TNF-α vaccines have generated encouraging data in animal models, however, data from clinical trials have not met expectations. In present study, we designed a TNF-α epitope-scaffold immunogen DTNF7 using the transmembrane domain of diphtheria toxin, named DTT as a scaffold. Molecular dynamics simulation shows that the grafted TNF-α epitope is entirely surface-exposed and presented in a native-like conformation while the rigid helical structure of DTT is minimally perturbed, thereby rendering the immunogen highly stable. Immunization of mice with alum formulated DTNF7 induced humoral responses against native TNF-α, and the antibody titer was sustained for more than 6 months, which supports a role of the universal CD4 T cell epitopes of DTT in breaking self-immune tolerance. In a mouse model of rheumatoid arthritis, DTNF7-alum vaccination markedly delayed the onset of collagen-induced arthritis, and reduced incidence as well as clinical score. DTT is presumed safe as an epitope carrier because a catalytic inactive mutant of diphtheria toxin, CRM197 has good clinical safety records as an active vaccine component. Taken all together, we show that DTT-based epitope vaccine is a promising strategy for prevention and treatment of autoimmune diseases.",2016 Sep 22,"['Zhang, Li', 'Wang, Jin', 'Xu, Aizhang', 'Zhong, Conghao', 'Lu, Wuguang', 'Deng, Li', 'Li, Rongxiu']",PLoS One,,,True
e96b011c26501fc8432fd96787fe0aba49a08e0b,PMC,Reduced Risk of Importing Ebola Virus Disease because of Travel Restrictions in 2014: A Retrospective Epidemiological Modeling Study,http://dx.doi.org/10.1371/journal.pone.0163418,PMC5033593,27657544,CC BY,"BACKGROUND: An epidemic of Ebola virus disease (EVD) from 2013–16 posed a serious risk of global spread during its early growth phase. A post-epidemic evaluation of the effectiveness of travel restrictions has yet to be conducted. The present study aimed to estimate the effectiveness of travel restrictions in reducing the risk of importation from mid-August to September, 2014, using a simple hazard-based statistical model. METHODOLOGY/PRINCIPAL FINDINGS: The hazard rate was modeled as an inverse function of the effective distance, an excellent predictor of disease spread, which was calculated from the airline transportation network. By analyzing datasets of the date of EVD case importation from the 15(th) of July to the 15(th) of September 2014, and assuming that the network structure changed from the 8(th) of August 2014 because of travel restrictions, parameters that characterized the hazard rate were estimated. The absolute risk reduction and relative risk reductions due to travel restrictions were estimated to be less than 1% and about 20%, respectively, for all models tested. Effectiveness estimates among African countries were greater than those for other countries outside Africa. CONCLUSIONS: The travel restrictions were not effective enough to expect the prevention of global spread of Ebola virus disease. It is more efficient to control the spread of disease locally during an early phase of an epidemic than to attempt to control the epidemic at international borders. Capacity building for local containment and coordinated and expedited international cooperation are essential to reduce the risk of global transmission.",2016 Sep 22,"['Otsuki, Shiori', 'Nishiura, Hiroshi']",PLoS One,,,True
983e9c303f6c0082aa4fad58a82da11a16262a01,PMC,High diversity of picornaviruses in rats from different continents revealed by deep sequencing,http://dx.doi.org/10.1038/emi.2016.90,PMC5034103,27530749,CC BY,"Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.",2016 Aug 17,"['Hansen, Thomas Arn', 'Mollerup, Sarah', 'Nguyen, Nam-phuong', 'White, Nicole E', 'Coghlan, Megan', 'Alquezar-Planas, David E', 'Joshi, Tejal', 'Jensen, Randi Holm', 'Fridholm, Helena', 'Kjartansdóttir, Kristín Rós', 'Mourier, Tobias', 'Warnow, Tandy', 'Belsham, Graham J', 'Bunce, Michael', 'Willerslev, Eske', 'Nielsen, Lars Peter', 'Vinner, Lasse', 'Hansen, Anders Johannes']",Emerg Microbes Infect,,,True
2e4ddad3f80f7e1cdad82f054190c0656b1e22a4,PMC,High diversity of picornaviruses in rats from different continents revealed by deep sequencing,http://dx.doi.org/10.1038/emi.2016.90,PMC5034103,27530749,CC BY,"Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.",2016 Aug 17,"['Hansen, Thomas Arn', 'Mollerup, Sarah', 'Nguyen, Nam-phuong', 'White, Nicole E', 'Coghlan, Megan', 'Alquezar-Planas, David E', 'Joshi, Tejal', 'Jensen, Randi Holm', 'Fridholm, Helena', 'Kjartansdóttir, Kristín Rós', 'Mourier, Tobias', 'Warnow, Tandy', 'Belsham, Graham J', 'Bunce, Michael', 'Willerslev, Eske', 'Nielsen, Lars Peter', 'Vinner, Lasse', 'Hansen, Anders Johannes']",Emerg Microbes Infect,,,False
3231d73e559bb36891c0740d05c33549d4d5ad16,PMC,High diversity of picornaviruses in rats from different continents revealed by deep sequencing,http://dx.doi.org/10.1038/emi.2016.90,PMC5034103,27530749,CC BY,"Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.",2016 Aug 17,"['Hansen, Thomas Arn', 'Mollerup, Sarah', 'Nguyen, Nam-phuong', 'White, Nicole E', 'Coghlan, Megan', 'Alquezar-Planas, David E', 'Joshi, Tejal', 'Jensen, Randi Holm', 'Fridholm, Helena', 'Kjartansdóttir, Kristín Rós', 'Mourier, Tobias', 'Warnow, Tandy', 'Belsham, Graham J', 'Bunce, Michael', 'Willerslev, Eske', 'Nielsen, Lars Peter', 'Vinner, Lasse', 'Hansen, Anders Johannes']",Emerg Microbes Infect,,,False
68fa5fdbeaeb3e7ff1859b3355c4c639a5784259,PMC,High diversity of picornaviruses in rats from different continents revealed by deep sequencing,http://dx.doi.org/10.1038/emi.2016.90,PMC5034103,27530749,CC BY,"Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.",2016 Aug 17,"['Hansen, Thomas Arn', 'Mollerup, Sarah', 'Nguyen, Nam-phuong', 'White, Nicole E', 'Coghlan, Megan', 'Alquezar-Planas, David E', 'Joshi, Tejal', 'Jensen, Randi Holm', 'Fridholm, Helena', 'Kjartansdóttir, Kristín Rós', 'Mourier, Tobias', 'Warnow, Tandy', 'Belsham, Graham J', 'Bunce, Michael', 'Willerslev, Eske', 'Nielsen, Lars Peter', 'Vinner, Lasse', 'Hansen, Anders Johannes']",Emerg Microbes Infect,,,False
ba25ee1675af879a4885ee4e2cf10fe91ef6fa04,PMC,High diversity of picornaviruses in rats from different continents revealed by deep sequencing,http://dx.doi.org/10.1038/emi.2016.90,PMC5034103,27530749,CC BY,"Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.",2016 Aug 17,"['Hansen, Thomas Arn', 'Mollerup, Sarah', 'Nguyen, Nam-phuong', 'White, Nicole E', 'Coghlan, Megan', 'Alquezar-Planas, David E', 'Joshi, Tejal', 'Jensen, Randi Holm', 'Fridholm, Helena', 'Kjartansdóttir, Kristín Rós', 'Mourier, Tobias', 'Warnow, Tandy', 'Belsham, Graham J', 'Bunce, Michael', 'Willerslev, Eske', 'Nielsen, Lars Peter', 'Vinner, Lasse', 'Hansen, Anders Johannes']",Emerg Microbes Infect,,,False
09affbdb095d902261d09f42aea0c24b932e6f84,PMC,High diversity of picornaviruses in rats from different continents revealed by deep sequencing,http://dx.doi.org/10.1038/emi.2016.90,PMC5034103,27530749,CC BY,"Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.",2016 Aug 17,"['Hansen, Thomas Arn', 'Mollerup, Sarah', 'Nguyen, Nam-phuong', 'White, Nicole E', 'Coghlan, Megan', 'Alquezar-Planas, David E', 'Joshi, Tejal', 'Jensen, Randi Holm', 'Fridholm, Helena', 'Kjartansdóttir, Kristín Rós', 'Mourier, Tobias', 'Warnow, Tandy', 'Belsham, Graham J', 'Bunce, Michael', 'Willerslev, Eske', 'Nielsen, Lars Peter', 'Vinner, Lasse', 'Hansen, Anders Johannes']",Emerg Microbes Infect,,,False
f0fd369a572627c9df84aa15af3932f2de39f7fc,PMC,High diversity of picornaviruses in rats from different continents revealed by deep sequencing,http://dx.doi.org/10.1038/emi.2016.90,PMC5034103,27530749,CC BY,"Outbreaks of zoonotic diseases in humans and livestock are not uncommon, and an important component in containment of such emerging viral diseases is rapid and reliable diagnostics. Such methods are often PCR-based and hence require the availability of sequence data from the pathogen. Rattus norvegicus (R. norvegicus) is a known reservoir for important zoonotic pathogens. Transmission may be direct via contact with the animal, for example, through exposure to its faecal matter, or indirectly mediated by arthropod vectors. Here we investigated the viral content in rat faecal matter (n=29) collected from two continents by analyzing 2.2 billion next-generation sequencing reads derived from both DNA and RNA. Among other virus families, we found sequences from members of the Picornaviridae to be abundant in the microbiome of all the samples. Here we describe the diversity of the picornavirus-like contigs including near-full-length genomes closely related to the Boone cardiovirus and Theiler's encephalomyelitis virus. From this study, we conclude that picornaviruses within R. norvegicus are more diverse than previously recognized. The virome of R. norvegicus should be investigated further to assess the full potential for zoonotic virus transmission.",2016 Aug 17,"['Hansen, Thomas Arn', 'Mollerup, Sarah', 'Nguyen, Nam-phuong', 'White, Nicole E', 'Coghlan, Megan', 'Alquezar-Planas, David E', 'Joshi, Tejal', 'Jensen, Randi Holm', 'Fridholm, Helena', 'Kjartansdóttir, Kristín Rós', 'Mourier, Tobias', 'Warnow, Tandy', 'Belsham, Graham J', 'Bunce, Michael', 'Willerslev, Eske', 'Nielsen, Lars Peter', 'Vinner, Lasse', 'Hansen, Anders Johannes']",Emerg Microbes Infect,,,False
fd23dc1e8db2de0724d76fdadf0fd2f675be960e,PMC,Converting monoclonal antibody-based immunotherapies from passive to active: bringing immune complexes into play,http://dx.doi.org/10.1038/emi.2016.97,PMC5034104,27530750,CC BY,"Monoclonal antibodies (mAbs), which currently constitute the main class of biotherapeutics, are now recognized as major medical tools that are increasingly being considered to fight severe viral infections. Indeed, the number of antiviral mAbs developed in recent years has grown exponentially. Although their direct effects on viral blunting have been studied in detail, their potential immunomodulatory actions have been overlooked until recently. The ability of antiviral mAbs to modulate antiviral immune responses in infected organisms has recently been revealed. More specifically, upon recognition of their cognate antigens, mAbs form immune complexes (ICs) that can be recognized by the Fc receptors expressed on different immune cells of infected individuals. This binding may be followed by the modulation of the host immune responses. Harnessing this immunomodulatory property may facilitate improvements in the therapeutic potential of antiviral mAbs. This review focuses on the role of ICs formed with different viral determinants and mAbs in the induction of antiviral immune responses in the context of both passive immunotherapies and vaccination strategies. Potential deleterious effects of ICs on the host immune response are also discussed.",2016 Aug 17,"['Lambour, Jennifer', 'Naranjo-Gomez, Mar', 'Piechaczyk, Marc', 'Pelegrin, Mireia']",Emerg Microbes Infect,,,True
e44632c9b598cac15ccda521e13c65ca9fcf7426,PMC,The Healthy Infant Nasal Transcriptome: A Benchmark Study,http://dx.doi.org/10.1038/srep33994,PMC5034274,27658638,CC BY,"Responses by resident cells are likely to play a key role in determining the severity of respiratory disease. However, sampling of the airways poses a significant challenge, particularly in infants and children. Here, we report a reliable method for obtaining nasal epithelial cell RNA from infants for genome-wide transcriptomic analysis, and describe baseline expression characteristics in an asymptomatic cohort. Nasal epithelial cells were collected by brushing of the inferior turbinates, and gene expression was interrogated by RNA-seq analysis. Reliable recovery of RNA occurred in the absence of adverse events. We observed high expression of epithelial cell markers and similarity to the transcriptome for intrapulmonary airway epithelial cells. We identified genes displaying low and high expression variability, both inherently, and in response to environmental exposures. The greatest gene expression differences in this asymptomatic cohort were associated with the presence of known pathogenic viruses and/or bacteria. Robust bacteria-associated gene expression patterns were significantly associated with the presence of Moraxella. In summary, we have developed a reliable method for interrogating the infant airway transcriptome by sampling the nasal epithelium. Our data demonstrates both the fidelity and feasibility of our methodology, and describes normal gene expression and variation within a healthy infant cohort.",2016 Sep 23,"['Chu, Chin-Yi', 'Qiu, Xing', 'Wang, Lu', 'Bhattacharya, Soumyaroop', 'Lofthus, Gerry', 'Corbett, Anthony', 'Holden-Wiltse, Jeanne', 'Grier, Alex', 'Tesini, Brenda', 'Gill, Steven R.', 'Falsey, Ann R.', 'Caserta, Mary T.', 'Walsh, Edward E.', 'Mariani, Thomas J.']",Sci Rep,,,True
669511bfee375dd73d141c494f53d027c903f734,PMC,The Healthy Infant Nasal Transcriptome: A Benchmark Study,http://dx.doi.org/10.1038/srep33994,PMC5034274,27658638,CC BY,"Responses by resident cells are likely to play a key role in determining the severity of respiratory disease. However, sampling of the airways poses a significant challenge, particularly in infants and children. Here, we report a reliable method for obtaining nasal epithelial cell RNA from infants for genome-wide transcriptomic analysis, and describe baseline expression characteristics in an asymptomatic cohort. Nasal epithelial cells were collected by brushing of the inferior turbinates, and gene expression was interrogated by RNA-seq analysis. Reliable recovery of RNA occurred in the absence of adverse events. We observed high expression of epithelial cell markers and similarity to the transcriptome for intrapulmonary airway epithelial cells. We identified genes displaying low and high expression variability, both inherently, and in response to environmental exposures. The greatest gene expression differences in this asymptomatic cohort were associated with the presence of known pathogenic viruses and/or bacteria. Robust bacteria-associated gene expression patterns were significantly associated with the presence of Moraxella. In summary, we have developed a reliable method for interrogating the infant airway transcriptome by sampling the nasal epithelium. Our data demonstrates both the fidelity and feasibility of our methodology, and describes normal gene expression and variation within a healthy infant cohort.",2016 Sep 23,"['Chu, Chin-Yi', 'Qiu, Xing', 'Wang, Lu', 'Bhattacharya, Soumyaroop', 'Lofthus, Gerry', 'Corbett, Anthony', 'Holden-Wiltse, Jeanne', 'Grier, Alex', 'Tesini, Brenda', 'Gill, Steven R.', 'Falsey, Ann R.', 'Caserta, Mary T.', 'Walsh, Edward E.', 'Mariani, Thomas J.']",Sci Rep,,,True
d75d565a2c7f9bc13b6dbb4fa45eb85e2a1c72cd,PMC,Model-Informed Risk Assessment and Decision Making for an Emerging Infectious Disease in the Asia-Pacific Region,http://dx.doi.org/10.1371/journal.pntd.0005018,PMC5035030,27661978,CC BY,"BACKGROUND: Effective response to emerging infectious disease (EID) threats relies on health care systems that can detect and contain localised outbreaks before they reach a national or international scale. The Asia-Pacific region contains low and middle income countries in which the risk of EID outbreaks is elevated and whose health care systems may require international support to effectively detect and respond to such events. The absence of comprehensive data on populations, health care systems and disease characteristics in this region makes risk assessment and decisions about the provision of such support challenging. METHODOLOGY/PRINCIPAL FINDINGS: We describe a mathematical modelling framework that can inform this process by integrating available data sources, systematically explore the effects of uncertainty, and provide estimates of outbreak risk under a range of intervention scenarios. We illustrate the use of this framework in the context of a potential importation of Ebola Virus Disease into the Asia-Pacific region. Results suggest that, across a wide range of plausible scenarios, preemptive interventions supporting the timely detection of early cases provide substantially greater reductions in the probability of large outbreaks than interventions that support health care system capacity after an outbreak has commenced. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates how, in the presence of substantial uncertainty about health care system infrastructure and other relevant aspects of disease control, mathematical models can be used to assess the constraints that limited resources place upon the ability of local health care systems to detect and respond to EID outbreaks in a timely and effective fashion. Our framework can help evaluate the relative impact of these constraints to identify resourcing priorities for health care system support, in order to inform principled and quantifiable decision making.",2016 Sep 23,"['Moss, Robert', 'Hickson, Roslyn I.', 'McVernon, Jodie', 'McCaw, James M.', 'Hort, Krishna', 'Black, Jim', 'Madden, John R.', 'Tran, Nhi H.', 'McBryde, Emma S.', 'Geard, Nicholas']",PLoS Negl Trop Dis,,,True
f0dbc87d51c4d8a07ff83c5fc53afac5f973a20a,PMC,Model-Informed Risk Assessment and Decision Making for an Emerging Infectious Disease in the Asia-Pacific Region,http://dx.doi.org/10.1371/journal.pntd.0005018,PMC5035030,27661978,CC BY,"BACKGROUND: Effective response to emerging infectious disease (EID) threats relies on health care systems that can detect and contain localised outbreaks before they reach a national or international scale. The Asia-Pacific region contains low and middle income countries in which the risk of EID outbreaks is elevated and whose health care systems may require international support to effectively detect and respond to such events. The absence of comprehensive data on populations, health care systems and disease characteristics in this region makes risk assessment and decisions about the provision of such support challenging. METHODOLOGY/PRINCIPAL FINDINGS: We describe a mathematical modelling framework that can inform this process by integrating available data sources, systematically explore the effects of uncertainty, and provide estimates of outbreak risk under a range of intervention scenarios. We illustrate the use of this framework in the context of a potential importation of Ebola Virus Disease into the Asia-Pacific region. Results suggest that, across a wide range of plausible scenarios, preemptive interventions supporting the timely detection of early cases provide substantially greater reductions in the probability of large outbreaks than interventions that support health care system capacity after an outbreak has commenced. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates how, in the presence of substantial uncertainty about health care system infrastructure and other relevant aspects of disease control, mathematical models can be used to assess the constraints that limited resources place upon the ability of local health care systems to detect and respond to EID outbreaks in a timely and effective fashion. Our framework can help evaluate the relative impact of these constraints to identify resourcing priorities for health care system support, in order to inform principled and quantifiable decision making.",2016 Sep 23,"['Moss, Robert', 'Hickson, Roslyn I.', 'McVernon, Jodie', 'McCaw, James M.', 'Hort, Krishna', 'Black, Jim', 'Madden, John R.', 'Tran, Nhi H.', 'McBryde, Emma S.', 'Geard, Nicholas']",PLoS Negl Trop Dis,,,True
42e321eedba25d380ae44d16cdf0bbdeab83d665,PMC,Divergent Sapovirus Strains and Infection Prevalence in Wild Carnivores in the Serengeti Ecosystem: A Long-Term Study,http://dx.doi.org/10.1371/journal.pone.0163548,PMC5035092,27661997,CC BY,"The genus Sapovirus, in the family Caliciviridae, includes enteric viruses of humans and domestic animals. Information on sapovirus infection of wildlife is limited and is currently lacking for any free-ranging wildlife species in Africa. By screening a large number of predominantly fecal samples (n = 631) obtained from five carnivore species in the Serengeti ecosystem, East Africa, sapovirus RNA was detected in the spotted hyena (Crocuta crocuta, family Hyaenidae), African lion (Panthera leo, family Felidae), and bat-eared fox (Otocyon megalotis, family Canidae), but not in golden or silver-backed jackals (Canis aureus and C. mesomelas, respectively, family Canidae). A phylogenetic analysis based on partial RNA-dependent RNA polymerase (RdRp) gene sequences placed the sapovirus strains from African carnivores in a monophyletic group. Within this monophyletic group, sapovirus strains from spotted hyenas formed one independent sub-group, and those from bat-eared fox and African lion a second sub-group. The percentage nucleotide similarity between sapoviruses from African carnivores and those from other species was low (< 70.4%). Long-term monitoring of sapovirus in a population of individually known spotted hyenas from 2001 to 2012 revealed: i) a relatively high overall infection prevalence (34.8%); ii) the circulation of several genetically diverse variants; iii) large fluctuations in infection prevalence across years, indicative of outbreaks; iv) no significant difference in the likelihood of infection between animals in different age categories. The likelihood of sapovirus infection decreased with increasing hyena group size, suggesting an encounter reduction effect, but was independent of socially mediated ano-genital contact, or the extent of the area over which an individual roamed.",2016 Sep 23,"['Olarte-Castillo, Ximena A.', 'Hofer, Heribert', 'Goller, Katja V.', 'Martella, Vito', 'Moehlman, Patricia D.', 'East, Marion L.']",PLoS One,,,True
8a77d1db3e7b6eb0cecfc42f737e4a437ea5f720,PMC,Divergent Sapovirus Strains and Infection Prevalence in Wild Carnivores in the Serengeti Ecosystem: A Long-Term Study,http://dx.doi.org/10.1371/journal.pone.0163548,PMC5035092,27661997,CC BY,"The genus Sapovirus, in the family Caliciviridae, includes enteric viruses of humans and domestic animals. Information on sapovirus infection of wildlife is limited and is currently lacking for any free-ranging wildlife species in Africa. By screening a large number of predominantly fecal samples (n = 631) obtained from five carnivore species in the Serengeti ecosystem, East Africa, sapovirus RNA was detected in the spotted hyena (Crocuta crocuta, family Hyaenidae), African lion (Panthera leo, family Felidae), and bat-eared fox (Otocyon megalotis, family Canidae), but not in golden or silver-backed jackals (Canis aureus and C. mesomelas, respectively, family Canidae). A phylogenetic analysis based on partial RNA-dependent RNA polymerase (RdRp) gene sequences placed the sapovirus strains from African carnivores in a monophyletic group. Within this monophyletic group, sapovirus strains from spotted hyenas formed one independent sub-group, and those from bat-eared fox and African lion a second sub-group. The percentage nucleotide similarity between sapoviruses from African carnivores and those from other species was low (< 70.4%). Long-term monitoring of sapovirus in a population of individually known spotted hyenas from 2001 to 2012 revealed: i) a relatively high overall infection prevalence (34.8%); ii) the circulation of several genetically diverse variants; iii) large fluctuations in infection prevalence across years, indicative of outbreaks; iv) no significant difference in the likelihood of infection between animals in different age categories. The likelihood of sapovirus infection decreased with increasing hyena group size, suggesting an encounter reduction effect, but was independent of socially mediated ano-genital contact, or the extent of the area over which an individual roamed.",2016 Sep 23,"['Olarte-Castillo, Ximena A.', 'Hofer, Heribert', 'Goller, Katja V.', 'Martella, Vito', 'Moehlman, Patricia D.', 'East, Marion L.']",PLoS One,,,False
8b544e8b7379e0e8f684ecba104f168adea0c9ce,PMC,Divergent Sapovirus Strains and Infection Prevalence in Wild Carnivores in the Serengeti Ecosystem: A Long-Term Study,http://dx.doi.org/10.1371/journal.pone.0163548,PMC5035092,27661997,CC BY,"The genus Sapovirus, in the family Caliciviridae, includes enteric viruses of humans and domestic animals. Information on sapovirus infection of wildlife is limited and is currently lacking for any free-ranging wildlife species in Africa. By screening a large number of predominantly fecal samples (n = 631) obtained from five carnivore species in the Serengeti ecosystem, East Africa, sapovirus RNA was detected in the spotted hyena (Crocuta crocuta, family Hyaenidae), African lion (Panthera leo, family Felidae), and bat-eared fox (Otocyon megalotis, family Canidae), but not in golden or silver-backed jackals (Canis aureus and C. mesomelas, respectively, family Canidae). A phylogenetic analysis based on partial RNA-dependent RNA polymerase (RdRp) gene sequences placed the sapovirus strains from African carnivores in a monophyletic group. Within this monophyletic group, sapovirus strains from spotted hyenas formed one independent sub-group, and those from bat-eared fox and African lion a second sub-group. The percentage nucleotide similarity between sapoviruses from African carnivores and those from other species was low (< 70.4%). Long-term monitoring of sapovirus in a population of individually known spotted hyenas from 2001 to 2012 revealed: i) a relatively high overall infection prevalence (34.8%); ii) the circulation of several genetically diverse variants; iii) large fluctuations in infection prevalence across years, indicative of outbreaks; iv) no significant difference in the likelihood of infection between animals in different age categories. The likelihood of sapovirus infection decreased with increasing hyena group size, suggesting an encounter reduction effect, but was independent of socially mediated ano-genital contact, or the extent of the area over which an individual roamed.",2016 Sep 23,"['Olarte-Castillo, Ximena A.', 'Hofer, Heribert', 'Goller, Katja V.', 'Martella, Vito', 'Moehlman, Patricia D.', 'East, Marion L.']",PLoS One,,,False
c29b35526bc17c92bdcc277b303bd6fc3ab57b0a,PMC,The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus,http://dx.doi.org/10.1186/s12918-016-0336-6,PMC5035469,27663205,CC BY,"BACKGROUND: The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation. RESULTS: We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine tumor necrosis factor alpha (TNFα) promote pathogenesis, presumably through excessive inflammation. CONCLUSIONS: The current study provides validation of network modeling approaches for identifying important players in virus infection pathogenesis, and a step forward in understanding the host response to an important infectious disease. The results presented here suggest the role of Kepi in the host response to SARS-CoV, as well as inflammatory activity driving pathogenesis through TNFα signaling in SARS-CoV infections. Though we have reported the utility of this approach in bacterial and cell culture studies previously, this is the first comprehensive study to confirm that network topology can be used to predict phenotypes in mice with experimental validation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12918-016-0336-6) contains supplementary material, which is available to authorized users.",2016 Sep 23,"['McDermott, Jason E.', 'Mitchell, Hugh D.', 'Gralinski, Lisa E.', 'Eisfeld, Amie J.', 'Josset, Laurence', 'Bankhead, Armand', 'Neumann, Gabriele', 'Tilton, Susan C.', 'Schäfer, Alexandra', 'Li, Chengjun', 'Fan, Shufang', 'McWeeney, Shannon', 'Baric, Ralph S.', 'Katze, Michael G.', 'Waters, Katrina M.']",BMC Syst Biol,,,False
671eba2ccb7c435efe6f91d4065f446a27c8efba,PMC,The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus,http://dx.doi.org/10.1186/s12918-016-0336-6,PMC5035469,27663205,CC BY,"BACKGROUND: The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation. RESULTS: We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine tumor necrosis factor alpha (TNFα) promote pathogenesis, presumably through excessive inflammation. CONCLUSIONS: The current study provides validation of network modeling approaches for identifying important players in virus infection pathogenesis, and a step forward in understanding the host response to an important infectious disease. The results presented here suggest the role of Kepi in the host response to SARS-CoV, as well as inflammatory activity driving pathogenesis through TNFα signaling in SARS-CoV infections. Though we have reported the utility of this approach in bacterial and cell culture studies previously, this is the first comprehensive study to confirm that network topology can be used to predict phenotypes in mice with experimental validation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12918-016-0336-6) contains supplementary material, which is available to authorized users.",2016 Sep 23,"['McDermott, Jason E.', 'Mitchell, Hugh D.', 'Gralinski, Lisa E.', 'Eisfeld, Amie J.', 'Josset, Laurence', 'Bankhead, Armand', 'Neumann, Gabriele', 'Tilton, Susan C.', 'Schäfer, Alexandra', 'Li, Chengjun', 'Fan, Shufang', 'McWeeney, Shannon', 'Baric, Ralph S.', 'Katze, Michael G.', 'Waters, Katrina M.']",BMC Syst Biol,,,False
a137eb51461b4a4ed3980aa5b9cb2f2c1cf0292a,PMC,The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus,http://dx.doi.org/10.1186/s12918-016-0336-6,PMC5035469,27663205,CC BY,"BACKGROUND: The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation. RESULTS: We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine tumor necrosis factor alpha (TNFα) promote pathogenesis, presumably through excessive inflammation. CONCLUSIONS: The current study provides validation of network modeling approaches for identifying important players in virus infection pathogenesis, and a step forward in understanding the host response to an important infectious disease. The results presented here suggest the role of Kepi in the host response to SARS-CoV, as well as inflammatory activity driving pathogenesis through TNFα signaling in SARS-CoV infections. Though we have reported the utility of this approach in bacterial and cell culture studies previously, this is the first comprehensive study to confirm that network topology can be used to predict phenotypes in mice with experimental validation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12918-016-0336-6) contains supplementary material, which is available to authorized users.",2016 Sep 23,"['McDermott, Jason E.', 'Mitchell, Hugh D.', 'Gralinski, Lisa E.', 'Eisfeld, Amie J.', 'Josset, Laurence', 'Bankhead, Armand', 'Neumann, Gabriele', 'Tilton, Susan C.', 'Schäfer, Alexandra', 'Li, Chengjun', 'Fan, Shufang', 'McWeeney, Shannon', 'Baric, Ralph S.', 'Katze, Michael G.', 'Waters, Katrina M.']",BMC Syst Biol,,,True
a3718ef8f5fc2e8b32992c568bc66646a870656c,PMC,Emergence of human caliciviruses among diarrhea cases in southwest China,http://dx.doi.org/10.1186/s12879-016-1831-5,PMC5035476,27663519,CC BY,"BACKGROUND: Acute diarrhea is one of the most serious problems in global public health that causes considerable morbidity and mortality worldwide. Human caliciviruses (HuCV) including norovirus (NoV, genogroup GI and GII) and sapovirus (SaV), is a leading cause of acute sporadic diarrhea in individuals across all age groups. However, few studies had been conducted clarifying the characteristics of HuCV in diarrhea cases across all age groups in China. Our study was aimed at assessing the HuCV-related diarrhea burden and NoV genotypes distribution in southwest China. METHODS: The study was conducted in four hospitals in Kunming city, Yunnan province, from June 2014 to July 2015. Stool specimens were collected from 1,121 diarrhea cases and 319 healthy controls in outpatient departments. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect NoV (GI, GII) and SaV. Sequencing was applied to confirm the three viral infections and phylogenetic analysis was performed to determine their genotypes. A structured questionnaire was used to record the demographic information and clinical symptoms of subjects. RESULTS: HuCV was detected at an 11.0 % infection rate in 1,121 diarrhea cases and at 3.4 % rate in 319 non-diarrhea subjects (p < 0.0001, OR = 3.5, 95 % CI 1.8–6.5). The prevalence of the NoV genogroup GII and genotype GII.4 in diarrhea cases was significantly higher than that found in healthy controls (p < 0.0001, p = 0.018, respectively). NoV GII (n = 118, 10.5 %) was the most common HuCV subtype in diarrhea cases, followed by SaV (n = 3, 0.3 %) and NoV GI (n = 2, 0.2 %). Of 118 NoV GII strains isolated from diarrhea patients. GII.4 (n = 55, 46.6 %) was the predominant strain, followed by GII.3 (n = 28, 23.7 %), GII.12 (n = 25, 21.2 %), GII.17 (n = 8, 6.8 %), and GII.5 (n = 2, 1.7 %). Of the 55 GII.4 strains, the GII.4 Sydney 2012 variant had absolutely predominant prevalence (n = 52, 94.5 %), followed by the NoV GII.4-2006b variant (n = 3, 5.5 %). The GII.4 Orleans 2009 variant was not found in diarrhea cases of the study. CONCLUSIONS: NoV GII was the major genogroup and GII.4 was the most predominant strain detected in diarrhea patients. The GII.17 is an emergent variant in sporadic diarrhea and might become the predominant strain in diarrhea cases in the near future. Rapid, accurate detection kits need to be developed to help us find and treat NoV-associated diarrhea in clinical settings in a timely manner.",2016 Sep 23,"['Zhang, Shun-Xian', 'Li, Li', 'Yin, Jian-Wen', 'Jin, Miao', 'Kong, Xiang-Yu', 'Pang, Li-Li', 'Zhou, Yong-Kang', 'Tian, Li-Guang', 'Chen, Jia-Xu', 'Zhou, Xiao-Nong']",BMC Infect Dis,,,True
b3d7fd02de63c9e801c668f9784a1f31be59cc97,PMC,Identification of a novel canine parvovirus type 2c in Taiwan,http://dx.doi.org/10.1186/s12985-016-0620-5,PMC5035481,27663840,CC BY,"BACKGROUND: Taiwan has been considered free from canine parvovirus type 2c (CPV-2c) based on the last report of canine parvovirus type 2 (CPV-2) surveillance. However, since January 2015, the first report of CPV-2c in a puppy has occurred in Taiwan. There is currently limited information about the CPV-2c variant in Taiwan. In the present study, we characterized the previously unidentified CPV-2c variant and investigated the distribution of CPV-2 variants in Taiwan. METHODS: During January 2014 to April 2016, fecal or rectal swab samples from 99 dogs with suspected CPV-2 infection in Taiwan were collected. Eighty-eight were identified as being either CPV-2a, −2b or -2c variants positive by real-time PCR and sequence analysis. RESULTS: Sequence analysis of the 88 isolates confirmed CPV-2c as the dominant variant (54.6 %), followed by CPV-2b (26.1 %) and CPV-2a (19.3 %). Phylogenetic analysis demonstrated that the recent CPV-2c variants are similar to the Chinese CPV-2c strain but can be considered as novel Asian CPV-2c isolates. CONCLUSION: The present study provides evidence for the existence of a novel CPV-2c variant in Taiwan. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0620-5) contains supplementary material, which is available to authorized users.",2016 Sep 23,"['Chiang, Shu-Yun', 'Wu, Hung-Yi', 'Chiou, Ming-Tang', 'Chang, Min-Chen', 'Lin, Chao-Nan']",Virol J,,,True
a293d2836c440402c8f71b2785b853473d188f5e,PMC,Bibliometric analysis of global scientific research on carbapenem resistance (1986–2015),http://dx.doi.org/10.1186/s12941-016-0169-6,PMC5035509,27663999,CC BY,"BACKGROUND: Antimicrobial resistance is a global public health challenge and carbapenem resistance, in particular, is considered an urgent global health threat. This study was carried out to give a bibliometric overview of literature on carbapenem resistance. In specific, number of publications, top productive countries and institutes, highly cited articles, citation analysis, co-authorships, international collaboration, top active authors, and journals publishing articles on carbapenem resistance were analyzed and discussed. METHODS: Specific keywords pertaining to carbapenem resistance were used in Scopus database. Quantitative and qualitative analysis of retrieved data were presented using appropriate bibliometric indicators and visualization maps. RESULTS: A total of 2617 journal articles were retrieved. The average number of citations per article was of 21.47. The growth of publications showed a dramatic increase from 2008 to 2015. Approximately 9 % of retrieved articles on carbapenem resistance were published in Antimicrobial Agents and Chemotherapy journal. Retrieved articles were published by 102 different countries. The United States of America (USA) contributed most with 437 (16.70 %) articles followed by China with 257 (9.82 %) articles. When productivity was stratified by population size, Greece ranked first followed by France. Greece also ranked first when data were stratified by gross domestic product (GDP). Asian countries have lesser international collaboration compared with other countries in the top ten list. Five of top ten productive institutes were Europeans (France, the UK, Greece, Italy, and Switzerland) and two were Asians (China and South Korea). Other active institutes included an Israeli and a Brazilian institute. Four of the top ten cited articles were published in Antimicrobial Agents and Chemotherapy journal and two were published in The Lancet Infectious Diseases. CONCLUSION: There was a dramatic increase in number of publications on carbapenem resistance in the past few years. These publications were produced from different world regions including Asia, Europe, Middle East, and Latin America. International collaboration needs to be encouraged particularly for researchers in Asia. Molecular biology and epidemiology dominated the theme of the top ten cited articles on carbapenem resistance. This bibliometric study will hopefully help health policy makers in planning future research and allocating funds pertaining to carbapenem resistance.",2016 Sep 23,"['Sweileh, Waleed M.', 'Shraim, Naser Y.', 'Al-Jabi, Samah W.', 'Sawalha, Ansam F.', 'AbuTaha, Adham S.', 'Zyoud, Sa’ed H.']",Ann Clin Microbiol Antimicrob,,,True
bee044e4101c6958db139f19f6dd751990c2ce85,PMC,"Novel highly divergent reassortant bat rotaviruses in Cameroon, without evidence of zoonosis",http://dx.doi.org/10.1038/srep34209,PMC5035928,27666390,CC BY,"Bats are an important reservoir for zoonotic viruses. To date, only three RVA strains have been reported in bats in Kenya and China. In the current study we investigated the genetic diversity of RVAs in fecal samples from 87 straw-colored fruit bats living in close contact with humans in Cameroon using viral metagenomics. Five (near) complete RVA genomes were obtained. A single RVA strain showed a partial relationship with the Kenyan bat RVA strain, whereas the other strains were completely novel. Only the VP7 and VP4 genes showed significant variability, indicating the occurrence of frequent reassortment events. Comparing these bat RVA strains with currently used human RVA screening primers indicated that most of the novel VP7 and VP4 segments would not be detected in routine epidemiological screening studies. Therefore, novel consensus screening primers were developed and used to screen samples from infants with gastroenteritis living in close proximity with the studied bat population. Although RVA infections were identified in 36% of the infants, there was no evidence of zoonosis. This study identified multiple novel bat RVA strains, but further epidemiological studies in humans will have to assess if these viruses have the potential to cause gastroenteritis in humans.",2016 Sep 26,"['Yinda, Claude Kwe', 'Zeller, Mark', 'Conceição-Neto, Nádia', 'Maes, Piet', 'Deboutte, Ward', 'Beller, Leen', 'Heylen, Elisabeth', 'Ghogomu, Stephen Mbigha', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",Sci Rep,,,True
afdacf564888d252a93303eb6f3407b8c3f3355c,PMC,"Novel highly divergent reassortant bat rotaviruses in Cameroon, without evidence of zoonosis",http://dx.doi.org/10.1038/srep34209,PMC5035928,27666390,CC BY,"Bats are an important reservoir for zoonotic viruses. To date, only three RVA strains have been reported in bats in Kenya and China. In the current study we investigated the genetic diversity of RVAs in fecal samples from 87 straw-colored fruit bats living in close contact with humans in Cameroon using viral metagenomics. Five (near) complete RVA genomes were obtained. A single RVA strain showed a partial relationship with the Kenyan bat RVA strain, whereas the other strains were completely novel. Only the VP7 and VP4 genes showed significant variability, indicating the occurrence of frequent reassortment events. Comparing these bat RVA strains with currently used human RVA screening primers indicated that most of the novel VP7 and VP4 segments would not be detected in routine epidemiological screening studies. Therefore, novel consensus screening primers were developed and used to screen samples from infants with gastroenteritis living in close proximity with the studied bat population. Although RVA infections were identified in 36% of the infants, there was no evidence of zoonosis. This study identified multiple novel bat RVA strains, but further epidemiological studies in humans will have to assess if these viruses have the potential to cause gastroenteritis in humans.",2016 Sep 26,"['Yinda, Claude Kwe', 'Zeller, Mark', 'Conceição-Neto, Nádia', 'Maes, Piet', 'Deboutte, Ward', 'Beller, Leen', 'Heylen, Elisabeth', 'Ghogomu, Stephen Mbigha', 'Van Ranst, Marc', 'Matthijnssens, Jelle']",Sci Rep,,,False
9c776ca426a931dbbd3e34cd0b817adb19add3f1,PMC,How Polyomaviruses Exploit the ERAD Machinery to Cause Infection,http://dx.doi.org/10.3390/v8090242,PMC5035956,27589785,CC BY,"To infect cells, polyomavirus (PyV) traffics from the cell surface to the endoplasmic reticulum (ER) where it hijacks elements of the ER-associated degradation (ERAD) machinery to penetrate the ER membrane and reach the cytosol. From the cytosol, the virus transports to the nucleus, enabling transcription and replication of the viral genome that leads to lytic infection or cellular transformation. How PyV exploits the ERAD machinery to cross the ER membrane and access the cytosol, a decisive infection step, remains enigmatic. However, recent studies have slowly unraveled many aspects of this process. These emerging insights should advance our efforts to develop more effective therapies against PyV-induced human diseases.",2016 Aug 29,"['Dupzyk, Allison', 'Tsai, Billy']",Viruses,,,True
8befe1b5905e502b127ae478f3b9de1d6e25e317,PMC,Arms Race between Enveloped Viruses and the Host ERAD Machinery,http://dx.doi.org/10.3390/v8090255,PMC5035969,27657106,CC BY,"Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during the infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed to potentiate or inhibit viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells.",2016 Sep 19,"['Frabutt, Dylan A.', 'Zheng, Yong-Hui']",Viruses,,,True
958d54d13cbc0341fe590ba4eeb59e2a0b4fca51,PMC,TRIM52 inhibits Japanese Encephalitis Virus replication by degrading the viral NS2A,http://dx.doi.org/10.1038/srep33698,PMC5035999,27667714,CC BY,"The members of tripartite-motif containing (TRIM) protein participate in various cellular processes and play an important role in host antiviral function. TRIM proteins exert their antiviral activity either directly by degrading viral proteins through their E3 ligase activity, or indirectly by promoting host innate immunity. This study demonstrated for the first time that TRIM52 is a novel antiviral TRIM protein against Japanese encephalitis virus (JEV) infection. Overexpression of TRIM52 restricted JEV replication in BHK-21 and 293T cells. In addition, JEV nonstructural protein 2A (NS2A) is a protein that interacts with TRIM52. Their interaction degraded NS2A in a proteasome-dependent manner via the E3 ligase activity of TRIM52. Thus, TRIM52 is a novel antiviral TRIM protein, and it exerted antiviral activity against JEV infection by targeting and degrading viral NS2A.",2016 Sep 26,"['Fan, Wenchun', 'Wu, Mengge', 'Qian, Suhong', 'Zhou, Yun', 'Chen, Huanchun', 'Li, Xiangmin', 'Qian, Ping']",Sci Rep,,,True
bba54a43464e4fda9280139894c5467524ef2faf,PMC,Rational improvement of gp41-targeting HIV-1 fusion inhibitors: an innovatively designed Ile-Asp-Leu tail with alternative conformations,http://dx.doi.org/10.1038/srep31983,PMC5036048,27666394,CC BY,"Peptides derived from the C-terminal heptad repeat (CHR) of HIV gp41 have been developed as effective fusion inhibitors against HIV-1, but facing the challenges of enhancing potency and stability. Here, we report a rationally designed novel HIV-1 fusion inhibitor derived from CHR-derived peptide (Trp628~Gln653, named CP), but with an innovative Ile-Asp-Leu tail (IDL) that dramatically increased the inhibitory activity by up to 100 folds. We also determined the crystal structures of artificial fusion peptides N36- and N43-L6-CP-IDL. Although the overall structures of both fusion peptides share the canonical six-helix bundle (6-HB) configuration, their IDL tails adopt two different conformations: a one-turn helix with the N36, and a hook-like structure with the longer N43. Structural comparison showed that the hook-like IDL tail possesses a larger interaction interface with NHR than the helical one. Further molecular dynamics simulations of the two 6-HBs and isolated CP-IDL peptides suggested that hook-like form of IDL tail can be stabilized by its binding to NHR trimer. Therefore, CP-IDL has potential for further development as a new HIV fusion inhibitor, and this strategy could be widely used in developing artificial fusion inhibitors against HIV and other enveloped viruses.",2016 Sep 26,"['Zhu, Yun', 'Su, Shan', 'Qin, Lili', 'Wang, Qian', 'Shi, Lei', 'Ma, Zhenxuan', 'Tang, Jianchao', 'Jiang, Shibo', 'Lu, Lu', 'Ye, Sheng', 'Zhang, Rongguang']",Sci Rep,,,True
8903ed70c0e66c2bad50f57df3c885f7253cc2b8,PMC,Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities,http://dx.doi.org/10.1038/ncomms12777,PMC5036131,27652979,CC BY,"Cyclophilins are peptidyl-prolyl cis/trans isomerases (PPIase) that catalyse the interconversion of the peptide bond at proline residues. Several cyclophilins play a pivotal role in the life cycle of a number of viruses. The existing cyclophilin inhibitors, all derived from cyclosporine A or sanglifehrin A, have disadvantages, including their size, potential for side effects unrelated to cyclophilin inhibition and drug–drug interactions, unclear antiviral spectrum and manufacturing issues. Here we use a fragment-based drug discovery approach using nucleic magnetic resonance, X-ray crystallography and structure-based compound optimization to generate a new family of non-peptidic, small-molecule cyclophilin inhibitors with potent in vitro PPIase inhibitory activity and antiviral activity against hepatitis C virus, human immunodeficiency virus and coronaviruses. This family of compounds has the potential for broad-spectrum, high-barrier-to-resistance treatment of viral infections.",2016 Sep 22,"['Ahmed-Belkacem, Abdelhakim', 'Colliandre, Lionel', 'Ahnou, Nazim', 'Nevers, Quentin', 'Gelin, Muriel', 'Bessin, Yannick', 'Brillet, Rozenn', 'Cala, Olivier', 'Douguet, Dominique', 'Bourguet, William', 'Krimm, Isabelle', 'Pawlotsky, Jean-Michel', 'Guichou, Jean- François']",Nat Commun,,,True
b16129cfc36efc5d85192fbaa31d96799c98f8c5,PMC,Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities,http://dx.doi.org/10.1038/ncomms12777,PMC5036131,27652979,CC BY,"Cyclophilins are peptidyl-prolyl cis/trans isomerases (PPIase) that catalyse the interconversion of the peptide bond at proline residues. Several cyclophilins play a pivotal role in the life cycle of a number of viruses. The existing cyclophilin inhibitors, all derived from cyclosporine A or sanglifehrin A, have disadvantages, including their size, potential for side effects unrelated to cyclophilin inhibition and drug–drug interactions, unclear antiviral spectrum and manufacturing issues. Here we use a fragment-based drug discovery approach using nucleic magnetic resonance, X-ray crystallography and structure-based compound optimization to generate a new family of non-peptidic, small-molecule cyclophilin inhibitors with potent in vitro PPIase inhibitory activity and antiviral activity against hepatitis C virus, human immunodeficiency virus and coronaviruses. This family of compounds has the potential for broad-spectrum, high-barrier-to-resistance treatment of viral infections.",2016 Sep 22,"['Ahmed-Belkacem, Abdelhakim', 'Colliandre, Lionel', 'Ahnou, Nazim', 'Nevers, Quentin', 'Gelin, Muriel', 'Bessin, Yannick', 'Brillet, Rozenn', 'Cala, Olivier', 'Douguet, Dominique', 'Bourguet, William', 'Krimm, Isabelle', 'Pawlotsky, Jean-Michel', 'Guichou, Jean- François']",Nat Commun,,,True
04ed44ad0aed30771e1ba0f38e4aa00101d1b8c3,PMC,A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques,http://dx.doi.org/10.1038/ncomms12838,PMC5036149,27653379,CC BY,"As the predominant aetiological agent of the common cold, human rhinovirus (HRV) is the leading cause of human infectious disease. Early studies showed that a monovalent formalin-inactivated HRV vaccine can be protective, and virus-neutralizing antibodies (nAb) correlated with protection. However, co-circulation of many HRV types discouraged further vaccine efforts. Here, we test the hypothesis that increasing virus input titres in polyvalent inactivated HRV vaccine may result in broad nAb responses. We show that serum nAb against many rhinovirus types can be induced by polyvalent, inactivated HRVs plus alhydrogel (alum) adjuvant. Using formulations up to 25-valent in mice and 50-valent in rhesus macaques, HRV vaccine immunogenicity was related to sufficient quantity of input antigens, and valency was not a major factor for potency or breadth of the response. Thus, we have generated a vaccine capable of inducing nAb responses to numerous and diverse HRV types.",2016 Sep 22,"['Lee, Sujin', 'Nguyen, Minh Trang', 'Currier, Michael G.', 'Jenkins, Joe B.', 'Strobert, Elizabeth A.', 'Kajon, Adriana E.', 'Madan-Lala, Ranjna', 'Bochkov, Yury A.', 'Gern, James E.', 'Roy, Krishnendu', 'Lu, Xiaoyan', 'Erdman, Dean D.', 'Spearman, Paul', 'Moore, Martin L.']",Nat Commun,,,True
fc8c37b262255f1af7df6aa9bbbce30f5d5aa20a,PMC,A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques,http://dx.doi.org/10.1038/ncomms12838,PMC5036149,27653379,CC BY,"As the predominant aetiological agent of the common cold, human rhinovirus (HRV) is the leading cause of human infectious disease. Early studies showed that a monovalent formalin-inactivated HRV vaccine can be protective, and virus-neutralizing antibodies (nAb) correlated with protection. However, co-circulation of many HRV types discouraged further vaccine efforts. Here, we test the hypothesis that increasing virus input titres in polyvalent inactivated HRV vaccine may result in broad nAb responses. We show that serum nAb against many rhinovirus types can be induced by polyvalent, inactivated HRVs plus alhydrogel (alum) adjuvant. Using formulations up to 25-valent in mice and 50-valent in rhesus macaques, HRV vaccine immunogenicity was related to sufficient quantity of input antigens, and valency was not a major factor for potency or breadth of the response. Thus, we have generated a vaccine capable of inducing nAb responses to numerous and diverse HRV types.",2016 Sep 22,"['Lee, Sujin', 'Nguyen, Minh Trang', 'Currier, Michael G.', 'Jenkins, Joe B.', 'Strobert, Elizabeth A.', 'Kajon, Adriana E.', 'Madan-Lala, Ranjna', 'Bochkov, Yury A.', 'Gern, James E.', 'Roy, Krishnendu', 'Lu, Xiaoyan', 'Erdman, Dean D.', 'Spearman, Paul', 'Moore, Martin L.']",Nat Commun,,,True
7acc1a3baf89f2341feebef298a6531b4f930794,PMC,Early diagnosis of dengue disease severity in a resource-limited Asian country,http://dx.doi.org/10.1186/s12879-016-1849-8,PMC5036306,27670906,CC BY,"BACKGROUND: Dengue is endemic throughout Cambodia, a country faced with significant health and economic challenges. We undertook a clinical study at the National Paediatric Hospital in Phnom Penh to evaluate clinical diagnostic parameters for dengue and predictors of disease outcome. METHODS: Between September 2011 and January 2013, all consecutive inpatients aged between 1 and 15 years and presenting with suspected dengue were enrolled. They were clinically assessed using both the 1997 and 2009 WHO dengue classifications. Specimens were collected upon admission and discharge and tested for dengue at Institut Pasteur in Cambodia. RESULTS: A total of 701 patients were screened. Of these, 79 % were dengue-confirmed by laboratory testing, and 21 % tested dengue-negative. A positive tourniquet test, absence of upper respiratory symptoms, leukopenia, thrombocytopenia, and elevated liver transaminases were independent predictors for laboratory-confirmed dengue among the children. The presence of several warning signs on hospital admission was associated with a concurrent laboratory-confirmed diagnosis of severe disease outcome. CONCLUSIONS: The presence of two or more warning signs was associated with a concurrent laboratory-confirmed diagnosis of severe dengue at hospital admission. Thus, a cumulative score combining simple clinical parameters and first-line laboratory findings could be used to accurately predict dengue virus infection in pediatric populations, optimizing triage in settings with limited laboratory resources. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1849-8) contains supplementary material, which is available to authorized users.",2016 Sep 26,"['Cavailler, Philippe', 'Tarantola, Arnaud', 'Leo, Yee Sin', 'Lover, Andrew A.', 'Rachline, Anne', 'Duch, Moniboth', 'Huy, Rekol', 'Quake, Ai Li', 'Kdan, Yuvatha', 'Duong, Veasna', 'Brett, Jeremy L.', 'Buchy, Philippe']",BMC Infect Dis,,,False
b21cd46320a65645b81f4187e79d00da23e72c4a,PMC,Early diagnosis of dengue disease severity in a resource-limited Asian country,http://dx.doi.org/10.1186/s12879-016-1849-8,PMC5036306,27670906,CC BY,"BACKGROUND: Dengue is endemic throughout Cambodia, a country faced with significant health and economic challenges. We undertook a clinical study at the National Paediatric Hospital in Phnom Penh to evaluate clinical diagnostic parameters for dengue and predictors of disease outcome. METHODS: Between September 2011 and January 2013, all consecutive inpatients aged between 1 and 15 years and presenting with suspected dengue were enrolled. They were clinically assessed using both the 1997 and 2009 WHO dengue classifications. Specimens were collected upon admission and discharge and tested for dengue at Institut Pasteur in Cambodia. RESULTS: A total of 701 patients were screened. Of these, 79 % were dengue-confirmed by laboratory testing, and 21 % tested dengue-negative. A positive tourniquet test, absence of upper respiratory symptoms, leukopenia, thrombocytopenia, and elevated liver transaminases were independent predictors for laboratory-confirmed dengue among the children. The presence of several warning signs on hospital admission was associated with a concurrent laboratory-confirmed diagnosis of severe disease outcome. CONCLUSIONS: The presence of two or more warning signs was associated with a concurrent laboratory-confirmed diagnosis of severe dengue at hospital admission. Thus, a cumulative score combining simple clinical parameters and first-line laboratory findings could be used to accurately predict dengue virus infection in pediatric populations, optimizing triage in settings with limited laboratory resources. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1849-8) contains supplementary material, which is available to authorized users.",2016 Sep 26,"['Cavailler, Philippe', 'Tarantola, Arnaud', 'Leo, Yee Sin', 'Lover, Andrew A.', 'Rachline, Anne', 'Duch, Moniboth', 'Huy, Rekol', 'Quake, Ai Li', 'Kdan, Yuvatha', 'Duong, Veasna', 'Brett, Jeremy L.', 'Buchy, Philippe']",BMC Infect Dis,,,False
1bef85a33a74c3d1765752da0e715fc3a46e00d8,PMC,Early diagnosis of dengue disease severity in a resource-limited Asian country,http://dx.doi.org/10.1186/s12879-016-1849-8,PMC5036306,27670906,CC BY,"BACKGROUND: Dengue is endemic throughout Cambodia, a country faced with significant health and economic challenges. We undertook a clinical study at the National Paediatric Hospital in Phnom Penh to evaluate clinical diagnostic parameters for dengue and predictors of disease outcome. METHODS: Between September 2011 and January 2013, all consecutive inpatients aged between 1 and 15 years and presenting with suspected dengue were enrolled. They were clinically assessed using both the 1997 and 2009 WHO dengue classifications. Specimens were collected upon admission and discharge and tested for dengue at Institut Pasteur in Cambodia. RESULTS: A total of 701 patients were screened. Of these, 79 % were dengue-confirmed by laboratory testing, and 21 % tested dengue-negative. A positive tourniquet test, absence of upper respiratory symptoms, leukopenia, thrombocytopenia, and elevated liver transaminases were independent predictors for laboratory-confirmed dengue among the children. The presence of several warning signs on hospital admission was associated with a concurrent laboratory-confirmed diagnosis of severe disease outcome. CONCLUSIONS: The presence of two or more warning signs was associated with a concurrent laboratory-confirmed diagnosis of severe dengue at hospital admission. Thus, a cumulative score combining simple clinical parameters and first-line laboratory findings could be used to accurately predict dengue virus infection in pediatric populations, optimizing triage in settings with limited laboratory resources. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1849-8) contains supplementary material, which is available to authorized users.",2016 Sep 26,"['Cavailler, Philippe', 'Tarantola, Arnaud', 'Leo, Yee Sin', 'Lover, Andrew A.', 'Rachline, Anne', 'Duch, Moniboth', 'Huy, Rekol', 'Quake, Ai Li', 'Kdan, Yuvatha', 'Duong, Veasna', 'Brett, Jeremy L.', 'Buchy, Philippe']",BMC Infect Dis,,,True
3ccac237e5fa57c9d28f59f0b9b8e58188edd29b,PMC,Influenza A Virus Polymerase Recruits the RNA Helicase DDX19 to Promote the Nuclear Export of Viral mRNAs,http://dx.doi.org/10.1038/srep33763,PMC5037575,27653209,CC BY,"Enhancing the knowledge of host factors that are required for efficient influenza A virus (IAV) replication is essential to address questions related to pathogenicity and to identify targets for antiviral drug development. Here we focused on the interplay between IAV and DExD-box RNA helicases (DDX), which play a key role in cellular RNA metabolism by remodeling RNA-RNA or RNA-protein complexes. We performed a targeted RNAi screen on 35 human DDX proteins to identify those involved in IAV life cycle. DDX19 was a major hit. In DDX19-depleted cells the accumulation of viral RNAs and proteins was delayed, and the production of infectious IAV particles was strongly reduced. We show that DDX19 associates with intronless, unspliced and spliced IAV mRNAs and promotes their nuclear export. In addition, we demonstrate an RNA-independent association between DDX19 and the viral polymerase, that is modulated by the ATPase activity of DDX19. Our results provide a model in which DDX19 is recruited to viral mRNAs in the nucleus of infected cells to enhance their nuclear export. Information gained from this virus-host interaction improves the understanding of both the IAV replication cycle and the cellular function of DDX19.",2016 Sep 22,"['Diot, Cédric', 'Fournier, Guillaume', 'Dos Santos, Mélanie', 'Magnus, Julie', 'Komarova, Anastasia', 'van der Werf, Sylvie', 'Munier, Sandie', 'Naffakh, Nadia']",Sci Rep,,,True
695fe9211e014d362cf1d7a04fb81add693c12c5,PMC,Influenza A Virus Polymerase Recruits the RNA Helicase DDX19 to Promote the Nuclear Export of Viral mRNAs,http://dx.doi.org/10.1038/srep33763,PMC5037575,27653209,CC BY,"Enhancing the knowledge of host factors that are required for efficient influenza A virus (IAV) replication is essential to address questions related to pathogenicity and to identify targets for antiviral drug development. Here we focused on the interplay between IAV and DExD-box RNA helicases (DDX), which play a key role in cellular RNA metabolism by remodeling RNA-RNA or RNA-protein complexes. We performed a targeted RNAi screen on 35 human DDX proteins to identify those involved in IAV life cycle. DDX19 was a major hit. In DDX19-depleted cells the accumulation of viral RNAs and proteins was delayed, and the production of infectious IAV particles was strongly reduced. We show that DDX19 associates with intronless, unspliced and spliced IAV mRNAs and promotes their nuclear export. In addition, we demonstrate an RNA-independent association between DDX19 and the viral polymerase, that is modulated by the ATPase activity of DDX19. Our results provide a model in which DDX19 is recruited to viral mRNAs in the nucleus of infected cells to enhance their nuclear export. Information gained from this virus-host interaction improves the understanding of both the IAV replication cycle and the cellular function of DDX19.",2016 Sep 22,"['Diot, Cédric', 'Fournier, Guillaume', 'Dos Santos, Mélanie', 'Magnus, Julie', 'Komarova, Anastasia', 'van der Werf, Sylvie', 'Munier, Sandie', 'Naffakh, Nadia']",Sci Rep,,,False
634d9f6010d3e4f1586f4382b5c5c89e316d58bd,PMC,Success of tumorsphere isolation from WHO grade IV gliomas does not correlate with the weight of fresh tumor specimens: an immunohistochemical characterization of tumorsphere differentiation,http://dx.doi.org/10.1186/s12935-016-0350-1,PMC5037893,27708549,CC BY,"BACKGROUND: A trend of stage-by-stage increase in tumorsphere (TS) formation from glioma samples has been reported. Despite this trend, not all surgical specimens give rise to TSs, even World Health Organization (WHO) grade IV gliomas. Furthermore, it has been reported that differences in overall survival of primary glioblastoma patients depends on the propensity of their tumors to form TSs. However, the weights of fresh specimens vary from one surgical isolate to the next. METHODS: Accordingly, we evaluated the relationship between the weights of surgical specimens in WHO grade IV gliomas with the capacity to isolate TSs. Thirty-five fresh WHO grade IV glioma specimens were separated into two groups, based on whether they were positive or negative for TS isolation, and the relationship between TS isolation and weight of surgical specimens was assessed. RESULTS: We observed no significant difference in the weights of surgical samples in the two groups, and found that the optimal weight of specimens for TSs isolation was 500 mg. CONCLUSION: Thus, contrary to our expectations, the ability to isolate TSs from WHO grade IV glioma specimens was not related to the weight of fresh specimens.",2016 Sep 27,"['Sung, Kyoung Su', 'Shim, Jin-Kyoung', 'Lee, Ji-Hyun', 'Kim, Se Hoon', 'Park, Sohee', 'Roh, Tae-Hoon', 'Moon, Ju Hyung', 'Kim, Eui-Hyun', 'Kim, Sun Ho', 'Lee, Su Jae', 'Huh, Yong Min', 'Kang, Seok-Gu', 'Chang, Jong Hee']",Cancer Cell Int,,,True
3f551bf91d2b52cadac39dbd62e7ae0f51066446,PMC,A Bat-Derived Putative Cross-Family Recombinant Coronavirus with a Reovirus Gene,http://dx.doi.org/10.1371/journal.ppat.1005883,PMC5038965,27676249,CC BY,"The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 has generated enormous interest in the biodiversity, genomics and cross-species transmission potential of coronaviruses, especially those from bats, the second most speciose order of mammals. Herein, we identified a novel coronavirus, provisionally designated Rousettus bat coronavirus GCCDC1 (Ro-BatCoV GCCDC1), in the rectal swab samples of Rousettus leschenaulti bats by using pan-coronavirus RT-PCR and next-generation sequencing. Although the virus is similar to Rousettus bat coronavirus HKU9 (Ro-BatCoV HKU9) in genome characteristics, it is sufficiently distinct to be classified as a new species according to the criteria defined by the International Committee of Taxonomy of Viruses (ICTV). More striking was that Ro-BatCoV GCCDC1 contained a unique gene integrated into the 3’-end of the genome that has no homologs in any known coronavirus, but which sequence and phylogeny analyses indicated most likely originated from the p10 gene of a bat orthoreovirus. Subgenomic mRNA and cellular-level observations demonstrated that the p10 gene is functional and induces the formation of cell syncytia. Therefore, here we report a putative heterologous inter-family recombination event between a single-stranded, positive-sense RNA virus and a double-stranded segmented RNA virus, providing insights into the fundamental mechanisms of viral evolution.",2016 Sep 27,"['Huang, Canping', 'Liu, William J.', 'Xu, Wen', 'Jin, Tao', 'Zhao, Yingze', 'Song, Jingdong', 'Shi, Yi', 'Ji, Wei', 'Jia, Hao', 'Zhou, Yongming', 'Wen, Honghua', 'Zhao, Honglan', 'Liu, Huaxing', 'Li, Hong', 'Wang, Qihui', 'Wu, Ying', 'Wang, Liang', 'Liu, Di', 'Liu, Guang', 'Yu, Hongjie', 'Holmes, Edward C.', 'Lu, Lin', 'Gao, George F.']",PLoS Pathog,,,True
b07bcd8179099f8a5e49b8a7a2530590da99403b,PMC,The Role of Antimicrobial Peptides in Influenza Virus Infection and Their Potential as Antiviral and Immunomodulatory Therapy,http://dx.doi.org/10.3390/ph9030053,PMC5039506,27608030,CC BY,"Influenza A virus (IAV) remains a major threat that can cause severe morbidity and mortality due to rapid genomic variation. Resistance of IAVs to current anti-IAV drugs has been emerging, and antimicrobial peptides (AMPs) have been considered to be potential candidates for novel treatment against IAV infection. AMPs are endogenous proteins playing important roles in host defense through direct antimicrobial and antiviral activities and through immunomodulatory effects. In this review, we will discuss the anti-IAV and immunomodulatory effects of classical AMPs (defensins and cathelicidins), and proteins more recently discovered to have AMP-like activity (histones and Alzheimer’s associated β-amyloid). We will discuss the interactions between AMPs and other host defense proteins. Major emphasis will be placed on novel synthetic AMPs derived from modification of natural proteins, and on potential methods of increasing expression of endogenous AMPs, since these approaches may lead to novel antiviral therapeutics.",2016 Sep 6,"['Hsieh, I-Ni', 'Hartshorn, Kevan L.']",Pharmaceuticals (Basel),,,True
06624de6d8b09e5db9ba01c4cc721583331a40b5,PMC,Coinfection of Chlamydiae and other Bacteria in Reactive Arthritis and Spondyloarthritis: Need for Future Research,http://dx.doi.org/10.3390/microorganisms4030030,PMC5039590,27681924,CC BY,"Reactive (inflammatory) arthritis has been known for many years to follow genital infection with the intracellular bacterial pathogen Chlamydia trachomatis in some individuals. Recent studies from several groups have demonstrated that a related bacterium, the respiratory pathogen Chlamydia pneumoniae, can elicit a similar arthritis. Studies of these organisms, and of a set of gastrointestinal pathogens also associated with engendering inflammatory arthritis, have been relatively extensive. However, reports focusing on coinfections with these and/or other organisms, and the effects of such coinfections on the host immune and other systems, have been rare. In this article, we review the extant data regarding infections by multiple pathogens in the joint as they relate to engendering arthritis, and we suggest a number of research areas that must be given a high priority if we are to understand, and therefore to treat in an effective manner, such arthritides.",2016 Aug 24,"['Zeidler, Henning', 'Hudson, Alan P']",Microorganisms,,,True
95e77fc95e5b3b35c8856061119f2474d61c6089,PMC,The hookworm Ancylostoma ceylanicum intestinal transcriptome provides a platform for selecting drug and vaccine candidates,http://dx.doi.org/10.1186/s13071-016-1795-8,PMC5039805,27677574,CC BY,"BACKGROUND: The intestine of hookworms contains enzymes and proteins involved in the blood-feeding process of the parasite and is therefore a promising source of possible vaccine antigens. One such antigen, the hemoglobin-digesting intestinal aspartic protease known as Na-APR-1 from the human hookworm Necator americanus, is currently a lead candidate antigen in clinical trials, as is Na-GST-1 a heme-detoxifying glutathione S-transferase. METHODS: In order to discover additional hookworm vaccine antigens, messenger RNA was obtained from the intestine of male hookworms, Ancylostoma ceylanicum, maintained in hamsters. RNA-seq was performed using Illumina high-throughput sequencing technology. The genes expressed in the hookworm intestine were compared with those expressed in the whole worm and those genes overexpressed in the parasite intestine transcriptome were further analyzed. RESULTS: Among the lead transcripts identified were genes encoding for proteolytic enzymes including an A. ceylanicum APR-1, but the most common proteases were cysteine-, serine-, and metallo-proteases. Also in abundance were specific transporters of key breakdown metabolites, including amino acids, glucose, lipids, ions and water; detoxifying and heme-binding glutathione S-transferases; a family of cysteine-rich/antigen 5/pathogenesis-related 1 proteins (CAP) previously found in high abundance in parasitic nematodes; C-type lectins; and heat shock proteins. These candidates will be ranked for downstream antigen target selection based on key criteria including abundance, uniqueness in the parasite versus the vertebrate host, as well as solubility and yield of expression. CONCLUSION: The intestinal transcriptome of A. ceylanicum provides useful information for the identification of proteins involved in the blood-feeding process, representing a first step towards a reverse vaccinology approach to a human hookworm vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1795-8) contains supplementary material, which is available to authorized users.",2016 Sep 27,"['Wei, Junfei', 'Damania, Ashish', 'Gao, Xin', 'Liu, Zhuyun', 'Mejia, Rojelio', 'Mitreva, Makedonka', 'Strych, Ulrich', 'Bottazzi, Maria Elena', 'Hotez, Peter J.', 'Zhan, Bin']",Parasit Vectors,,,False
a53cae6e96975f86052ebaee23f1b83f8b90d175,PMC,The hookworm Ancylostoma ceylanicum intestinal transcriptome provides a platform for selecting drug and vaccine candidates,http://dx.doi.org/10.1186/s13071-016-1795-8,PMC5039805,27677574,CC BY,"BACKGROUND: The intestine of hookworms contains enzymes and proteins involved in the blood-feeding process of the parasite and is therefore a promising source of possible vaccine antigens. One such antigen, the hemoglobin-digesting intestinal aspartic protease known as Na-APR-1 from the human hookworm Necator americanus, is currently a lead candidate antigen in clinical trials, as is Na-GST-1 a heme-detoxifying glutathione S-transferase. METHODS: In order to discover additional hookworm vaccine antigens, messenger RNA was obtained from the intestine of male hookworms, Ancylostoma ceylanicum, maintained in hamsters. RNA-seq was performed using Illumina high-throughput sequencing technology. The genes expressed in the hookworm intestine were compared with those expressed in the whole worm and those genes overexpressed in the parasite intestine transcriptome were further analyzed. RESULTS: Among the lead transcripts identified were genes encoding for proteolytic enzymes including an A. ceylanicum APR-1, but the most common proteases were cysteine-, serine-, and metallo-proteases. Also in abundance were specific transporters of key breakdown metabolites, including amino acids, glucose, lipids, ions and water; detoxifying and heme-binding glutathione S-transferases; a family of cysteine-rich/antigen 5/pathogenesis-related 1 proteins (CAP) previously found in high abundance in parasitic nematodes; C-type lectins; and heat shock proteins. These candidates will be ranked for downstream antigen target selection based on key criteria including abundance, uniqueness in the parasite versus the vertebrate host, as well as solubility and yield of expression. CONCLUSION: The intestinal transcriptome of A. ceylanicum provides useful information for the identification of proteins involved in the blood-feeding process, representing a first step towards a reverse vaccinology approach to a human hookworm vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1795-8) contains supplementary material, which is available to authorized users.",2016 Sep 27,"['Wei, Junfei', 'Damania, Ashish', 'Gao, Xin', 'Liu, Zhuyun', 'Mejia, Rojelio', 'Mitreva, Makedonka', 'Strych, Ulrich', 'Bottazzi, Maria Elena', 'Hotez, Peter J.', 'Zhan, Bin']",Parasit Vectors,,,True
ca73d739c9c8c6ddb081d0badcea76f821ae147a,PMC,Rescue of the 1947 Zika Virus Prototype Strain with a Cytomegalovirus Promoter-Driven cDNA Clone,http://dx.doi.org/10.1128/mSphere.00246-16,PMC5040786,27704051,CC BY,"The recent Zika virus (ZIKV) outbreak has been linked to severe pathogenesis. Here, we report the construction of a plasmid carrying a cytomegalovirus (CMV) promoter-expressed prototype 1947 Uganda MR766 ZIKV cDNA that can initiate infection following direct plasmid DNA transfection of mammalian cells. Incorporation of a synthetic intron in the nonstructural protein 1 (NS1) region of the ZIKV polyprotein reduced viral cDNA-associated toxicity in bacteria. High levels of infectious virus were produced following transfection of the plasmid bearing the wild-type MR766 ZIKV genome, but not one with a disruption to the viral nonstructural protein 5 (NS5) polymerase active site. Multicycle growth curve and plaque assay experiments indicated that the MR766 virus resulting from plasmid transfection exhibited growth characteristics that were more similar to its parental isolate than previously published 2010 Cambodia and 2015 Brazil cDNA-rescued ZIKV. This ZIKV infectious clone will be useful for investigating the genetic determinants of ZIKV infection and pathogenesis and should be amenable to construction of diverse infectious clones expressing reporter proteins and representing a range of ZIKV isolates. IMPORTANCE The study of ZIKV, which has become increasingly important with the recent association of this virus with microcephaly and Guillain-Barré syndrome, would benefit from an efficient strategy to genetically manipulate the virus. This work describes a model system to produce infectious virus in cell culture. We created a plasmid carrying the prototype 1947 Uganda MR766 ZIKV genome that both was stable in bacteria and could produce high levels of infectious virus in mammalian cells through direct delivery of this DNA. Furthermore, growth properties of this rescued virus closely resembled those of the viral isolate from which it was derived. This model system will provide a simple and effective means to study how ZIKV genetics impact viral replication and pathogenesis.",2016 Sep 28,"['Schwarz, Megan C.', 'Sourisseau, Marion', 'Espino, Michael M.', 'Gray, Essanna S.', 'Chambers, Matthew T.', 'Tortorella, Domenico', 'Evans, Matthew J.']",mSphere,,,True
35ccd353aa1b7ee2a015dc8012a3bcc19a8f9a20,PMC,Strongyloides Hyperinfection Syndrome Combined with Cytomegalovirus Infection,http://dx.doi.org/10.1155/2016/1786265,PMC5040796,27703835,CC BY,"The mortality in Strongyloides hyperinfection syndrome (SHS) is alarmingly high. This is particularly common in bone marrow, renal, and other solid organ transplant (SOT) patients, where figures may reach up to 50–85%. Immunosuppressives, principally corticosteroids, are the primary triggering factor. In general, the clinical features of Strongyloides stercoralis hyperinfection are nonspecific; therefore, a high index of suspicion is required for early diagnosis and starting appropriate therapy. Although recurrent Gram-negative sepsis and meningitis have been previously reported, the combination of both cytomegalovirus (CMV) and strongyloidiasis had rarely been associated. We here describe a patient who survived SHS with recurrent Escherichia coli (E. coli) urosepsis and CMV infection.",2016 Sep 15,"['Elzein, Fatehi Elnour', 'Alsaeed, Mohammed', 'Ballool, Sulafa', 'Attia, Ashraf']",Case Rep Transplant,,,True
75a8ca179e8e0405a9c150507809c0f5c38aedb5,PMC,Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus,http://dx.doi.org/10.1038/srep34108,PMC5040956,27682426,CC BY,"The lack of a licensed vaccine for respiratory syncytial virus (RSV) can be partly attributed to regulatory hurdles resulting from vaccine enhanced respiratory disease (ERD) subsequent to natural RSV infection that was observed in clinical trials of formalin-inactivated RSV (FI-RSV) in antigen-naïve infants. To develop an effective vaccine that does not enhance RSV illness, it is important to understand how formalin and heat inactivation affected the antigenicity and immunogenicity of FI-RSV compared to native virus. Informed by atomic structures of RSV fusion (F) glycoprotein in prefusion (pre-F) and postfusion (post-F) conformations, we demonstrate that FI-RSV predominately presents post-F on the virion surface, whereas infectious RSV presents both pre-F and post-F conformations. This significant antigenic distinction has not been previously appreciated. Thus, a stabilized pre-F antigen is more representative of live RSV than F in its post-F conformation, as displayed on the surface of FI-RSV. This finding has major implications for discriminating current pre-F-based immunogens from FI-RSV used in historical vaccine trials.",2016 Sep 29,"['Killikelly, April M.', 'Kanekiyo, Masaru', 'Graham, Barney S.']",Sci Rep,,,True
f236858559d164c23558a5183e0c9302c5269e3c,PMC,Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus,http://dx.doi.org/10.1038/srep34108,PMC5040956,27682426,CC BY,"The lack of a licensed vaccine for respiratory syncytial virus (RSV) can be partly attributed to regulatory hurdles resulting from vaccine enhanced respiratory disease (ERD) subsequent to natural RSV infection that was observed in clinical trials of formalin-inactivated RSV (FI-RSV) in antigen-naïve infants. To develop an effective vaccine that does not enhance RSV illness, it is important to understand how formalin and heat inactivation affected the antigenicity and immunogenicity of FI-RSV compared to native virus. Informed by atomic structures of RSV fusion (F) glycoprotein in prefusion (pre-F) and postfusion (post-F) conformations, we demonstrate that FI-RSV predominately presents post-F on the virion surface, whereas infectious RSV presents both pre-F and post-F conformations. This significant antigenic distinction has not been previously appreciated. Thus, a stabilized pre-F antigen is more representative of live RSV than F in its post-F conformation, as displayed on the surface of FI-RSV. This finding has major implications for discriminating current pre-F-based immunogens from FI-RSV used in historical vaccine trials.",2016 Sep 29,"['Killikelly, April M.', 'Kanekiyo, Masaru', 'Graham, Barney S.']",Sci Rep,,,False
206231b403edaaa8ff0fd1a23ca2428dd261507b,PMC,Endophytes: A Treasure House of Bioactive Compounds of Medicinal Importance,http://dx.doi.org/10.3389/fmicb.2016.01538,PMC5041141,27746767,CC BY,"Endophytes are an endosymbiotic group of microorganisms that colonize in plants and microbes that can be readily isolated from any microbial or plant growth medium. They act as reservoirs of novel bioactive secondary metabolites, such as alkaloids, phenolic acids, quinones, steroids, saponins, tannins, and terpenoids that serve as a potential candidate for antimicrobial, anti-insect, anticancer and many more properties. While plant sources are being extensively explored for new chemical entities for therapeutic purposes, endophytic microbes also constitute an important source for drug discovery. This review aims to comprehend the contribution and uses of endophytes as an impending source of drugs against various forms of diseases and other possible medicinal use.",2016 Sep 29,"['Gouda, Sushanto', 'Das, Gitishree', 'Sen, Sandeep K.', 'Shin, Han-Seung', 'Patra, Jayanta Kumar']",Front Microbiol,,,True
2f0c1ffd323fc118bfa8cdd80142b126416423f9,PMC,The Golgi associated ERI3 is a Flavivirus host factor,http://dx.doi.org/10.1038/srep34379,PMC5041148,27682269,CC BY,"Dengue virus (DENV) is a mosquito-borne Flavivirus classified into four serotypes (DENV-1-4) that causes Dengue fever (DF), Dengue hemorrhagic Fever (DHF) or Dengue shock syndrome (DSS). An estimated 390 million people are at risk for infection with DENV and there are no effective vaccines or therapeutics. We utilized RNA chromatography coupled with quantitative mass spectrometry (qMS) to identify host RNA binding proteins (RBPs) that interact with DENV-2 RNA. We identified ERI3 (also PRNPIP and PINT1), a putative 3′–5′ RNA exonuclease, which preferentially associates with DENV-2 genomic RNA via interactions with dumbbell structures in the 3′ UTR. ERI3 is required for accumulation of DENV-2 genomic RNA and production of infectious particles. Furthermore, the mosquito homologue of ERI3 is required for DENV-2 replication in adult Aedes aegypti mosquitos implying that the requirement for ERI3 is conserved in both DENV hosts. In human cells ERI3 localizes to the Golgi in uninfected cells, but relocalizes near sites of DENV-2 replication in infected cells. ERI3 is not required for maintaining DENV-2 RNA stability or translation of the viral polyprotein, but is required for viral RNA synthesis. Our results define a specific role for ERI3 and highlight the importance of Golgi proteins in DENV-2 replication.",2016 Sep 29,"['Ward, Alex Michael', 'Calvert, Meredith E. K.', 'Read, Leah R.', 'Kang, Seokyoung', 'Levitt, Brandt E.', 'Dimopoulos, George', 'Bradrick, Shelton S.', 'Gunaratne, Jayantha', 'Garcia-Blanco, Mariano A.']",Sci Rep,,,True
dc46a9c2a3b3f5f7f3b6650c6fba4369a2793cd2,PMC,The Golgi associated ERI3 is a Flavivirus host factor,http://dx.doi.org/10.1038/srep34379,PMC5041148,27682269,CC BY,"Dengue virus (DENV) is a mosquito-borne Flavivirus classified into four serotypes (DENV-1-4) that causes Dengue fever (DF), Dengue hemorrhagic Fever (DHF) or Dengue shock syndrome (DSS). An estimated 390 million people are at risk for infection with DENV and there are no effective vaccines or therapeutics. We utilized RNA chromatography coupled with quantitative mass spectrometry (qMS) to identify host RNA binding proteins (RBPs) that interact with DENV-2 RNA. We identified ERI3 (also PRNPIP and PINT1), a putative 3′–5′ RNA exonuclease, which preferentially associates with DENV-2 genomic RNA via interactions with dumbbell structures in the 3′ UTR. ERI3 is required for accumulation of DENV-2 genomic RNA and production of infectious particles. Furthermore, the mosquito homologue of ERI3 is required for DENV-2 replication in adult Aedes aegypti mosquitos implying that the requirement for ERI3 is conserved in both DENV hosts. In human cells ERI3 localizes to the Golgi in uninfected cells, but relocalizes near sites of DENV-2 replication in infected cells. ERI3 is not required for maintaining DENV-2 RNA stability or translation of the viral polyprotein, but is required for viral RNA synthesis. Our results define a specific role for ERI3 and highlight the importance of Golgi proteins in DENV-2 replication.",2016 Sep 29,"['Ward, Alex Michael', 'Calvert, Meredith E. K.', 'Read, Leah R.', 'Kang, Seokyoung', 'Levitt, Brandt E.', 'Dimopoulos, George', 'Bradrick, Shelton S.', 'Gunaratne, Jayantha', 'Garcia-Blanco, Mariano A.']",Sci Rep,,,True
35fd455662a4a9c03d3791ee3a390c163a53f242,PMC,Phage display as a promising approach for vaccine development,http://dx.doi.org/10.1186/s12929-016-0285-9,PMC5041315,27680328,CC BY,"Bacteriophages are specific antagonists to bacterial hosts. These viral entities have attracted growing interest as optimal vaccine delivery vehicles. Phages are well-matched for vaccine design due to being highly stable under harsh environmental conditions, simple and inexpensive large scale production, and potent adjuvant capacities. Phage vaccines have efficient immunostimulatory effects and present a high safety profile because these viruses have made a constant relationship with the mammalian body during a long-standing evolutionary period. The birth of phage display technology has been a turning point in the development of phage-based vaccines. Phage display vaccines are made by expressing multiple copies of an antigen on the surface of immunogenic phage particles, thereby eliciting a powerful and effective immune response. Also, the ability to produce combinatorial peptide libraries with a highly diverse pool of randomized ligands has transformed phage display into a straightforward, versatile and high throughput screening methodology for the identification of potential vaccine candidates against different diseases in particular microbial infections. These libraries can be conveniently screened through an affinity selection-based strategy called biopanning against a wide variety of targets for the selection of mimotopes with high antigenicity and immunogenicity. Also, they can be panned against the antiserum of convalescent individuals to recognize novel peptidomimetics of pathogen-related epitopes. Phage display has represented enormous promise for finding new strategies of vaccine discovery and production and current breakthroughs promise a brilliant future for the development of different phage-based vaccine platforms.",2016 Sep 29,"['Aghebati-Maleki, Leili', 'Bakhshinejad, Babak', 'Baradaran, Behzad', 'Motallebnezhad, Morteza', 'Aghebati-Maleki, Ali', 'Nickho, Hamid', 'Yousefi, Mehdi', 'Majidi, Jafar']",J Biomed Sci,,,True
40f52a42602489ad329c93edf69e213267303c1f,PMC,Mandating influenza vaccinations for health care workers: analysing opportunities for policy change using Kingdon’s agenda setting framework,http://dx.doi.org/10.1186/s12913-016-1772-0,PMC5041441,27682853,CC BY,"BACKGROUND: The consequences of annual influenza outbreaks are often underestimated by the general public. Influenza poses a serious public health threat around the world, particularly for the most vulnerable populations. Fortunately, vaccination can mitigate the negative effects of this common infectious disease. Although inoculating frontline health care workers (HCWs) helps minimize disease transmission, some HCWs continue to resist participating in voluntary immunization programs. A potential solution to this problem is government-mandated vaccination for HCWs; however, in practice, there are substantial barriers to the adoption of such policies. The purpose of this paper is to identify the likelihood of adopting a policy for mandatory immunization of HCWs in Ontario based on a historical review of barriers to the agenda setting process. METHODS: Documents from secondary data sources were analysed using Kingdon’s agenda setting framework of three converging streams leading to windows of opportunity for possible policy adoption. RESULTS: The problems, politics, and policies streams of Kingdon’s framework have converged and diverged repeatedly over an extended period (policy windows have opened and closed several times). In each instance, a technically feasible solution was available. However, despite the evidence supporting the value of HCW immunization, alignment of the three agenda setting streams occurred for very short periods of time, during which, opposition lobby groups reacted, making the proposed solution less politically acceptable. CONCLUSIONS: Prior to the adoption of any new policies, issues must reach a government’s decision agenda. Based on Kingdon’s agenda setting framework, this only occurs when there is alignment of the problems, politics, and policies streams. Understanding this process makes it easier to predict the likelihood of a policy being adopted, and ultimately implemented. Such learning may be applied to policy issues in other jurisdictions. In the case of mandatory influenza vaccinations for HCWs in Ontario, it seems highly unlikely that a new policy will be adopted until perception of the problem’s importance is sufficient to overcome the political opposition to implementing a solution and thus, create a window of opportunity that is open long enough to support change.",2016 Sep 29,"['Jackson-Lee, Angela', 'Barr, Neil G.', 'Randall, Glen E.']",BMC Health Serv Res,,,True
50ad279de0a3f825b6280e07afc79439f59ecc3a,PMC,XB130 deficiency enhances lipopolysaccharide-induced septic response and acute lung injury,http://dx.doi.org/10.18632/oncotarget.8326,PMC5041914,27029000,CC BY,"XB130 is a novel oncoprotein that promotes cancer cell survival, proliferation and migration. Its physiological function in vivo is largely unknown. The objective of this study was to determine the role of XB130 in lipopolysaccharide (LPS)-induced septic responses and acute lung injury. LPS was intraperitoneally administrated to Xb130 knockout (KO) and wild type (WT) mice. There was a significant weight loss in KO mice at Day 2 and significantly higher disease scores during the 7 days of observation. The levels of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6 and interleukin-10 in the serum were significantly higher in KO mice at Day 2. In KO mice there were a significantly higher lung injury score, higher wet/dry lung weight ratio, more apoptotic cells and less proliferative cells in the lung. Macrophage infiltration was significantly elevated in the lung of KO mice. There was significantly increased number of p-GSK-3β positive cells in KO mice, which were mainly neutrophils and macrophages. XB130 is expressed in alveolar type I and type II cells in the lung. The expression in these cells was significantly reduced after LPS challenge. XB130 deficiency delayed the recovery from systemic septic responses, and the presence of XB130 in the alveolar epithelial cells may provide protective mechanisms by reducing cell death and promoting cell proliferation, and reducing pulmonary permeability.",2016 Mar 23,"['Toba, Hiroaki', 'Tomankova, Tereza', 'Wang, Yingchun', 'Bai, Xiaohui', 'Cho, Hae-Ra', 'Guan, Zhehong', 'Adeyi, Oyedele A.', 'Tian, Feng', 'Keshavjee, Shaf', 'Liu, Mingyao']",Oncotarget,,,True
fbe53eb3d1e68e9fc27b44c51e31a039c08aeb52,PMC,XB130 deficiency enhances lipopolysaccharide-induced septic response and acute lung injury,http://dx.doi.org/10.18632/oncotarget.8326,PMC5041914,27029000,CC BY,"XB130 is a novel oncoprotein that promotes cancer cell survival, proliferation and migration. Its physiological function in vivo is largely unknown. The objective of this study was to determine the role of XB130 in lipopolysaccharide (LPS)-induced septic responses and acute lung injury. LPS was intraperitoneally administrated to Xb130 knockout (KO) and wild type (WT) mice. There was a significant weight loss in KO mice at Day 2 and significantly higher disease scores during the 7 days of observation. The levels of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6 and interleukin-10 in the serum were significantly higher in KO mice at Day 2. In KO mice there were a significantly higher lung injury score, higher wet/dry lung weight ratio, more apoptotic cells and less proliferative cells in the lung. Macrophage infiltration was significantly elevated in the lung of KO mice. There was significantly increased number of p-GSK-3β positive cells in KO mice, which were mainly neutrophils and macrophages. XB130 is expressed in alveolar type I and type II cells in the lung. The expression in these cells was significantly reduced after LPS challenge. XB130 deficiency delayed the recovery from systemic septic responses, and the presence of XB130 in the alveolar epithelial cells may provide protective mechanisms by reducing cell death and promoting cell proliferation, and reducing pulmonary permeability.",2016 Mar 23,"['Toba, Hiroaki', 'Tomankova, Tereza', 'Wang, Yingchun', 'Bai, Xiaohui', 'Cho, Hae-Ra', 'Guan, Zhehong', 'Adeyi, Oyedele A.', 'Tian, Feng', 'Keshavjee, Shaf', 'Liu, Mingyao']",Oncotarget,,,False
2ebb6c8bf24d0955f26398dcc7653b0f6fb5c9f7,PMC,"Transgenic Mice Expressing MCP-1 by the Urothelium Demonstrate Bladder Hypersensitivity, Pelvic Pain and Voiding Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study",http://dx.doi.org/10.1371/journal.pone.0163829,PMC5042429,27684718,CC BY,"Monocyte chemoattractant protein-1 (MCP-1) is one of the key chemokines that play important roles in diverse inflammatory and chronic pain conditions. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating inflammatory condition of the urinary bladder characterized by the hallmark symptoms of pelvic pain and voiding dysfunction. To facilitate IC/BPS research, we used transgenic technology to develop a novel urothelial MCP-1 secretion mouse model (URO-MCP-1). A transgene consisting of the uroplakin II gene promoter and the mouse MCP-1 coding sequence with a secretory element was constructed and microinjected. URO-MCP-1 mice were found to express MCP-1 mRNA in the bladder epithelium and MCP-1 protein in the urine, and developed bladder inflammation 24 hours after intravesical administration of a single sub-noxious dose of lipopolysaccharide (LPS). The inflamed bladders of URO-MCP-1 mice exhibited elevated mRNAs for interleukin (IL)-1ß, IL-6, substance P precursor, and nerve growth factor as well as increased macrophage infiltration. In parallel with these phenotypic changes, URO-MCP-1 mice manifested significant functional changes at days 1 and 3 after cystitis induction. These functional changes included pelvic pain as measured by von Frey filament stimulation and voiding dysfunction (increased urinary frequency, reduced average volume voided per micturition, and reduced maximum volume voided per micturition) as measured by micturition cages. Micturition changes remained evident at day 7 after cystitis induction, although these changes were not statistically significant. Control wild-type C57BL/6 mice manifested no clear changes in histological, biochemical and behavioral features after similar cystitis induction with LPS. Taken together, our results indicate that URO-MCP-1 mice are hypersensitive to bladder irritants such as LPS and develop pelvic pain and voiding dysfunction upon cystitis induction, providing a novel model for IC/BPS research.",2016 Sep 29,"['Xu, Suming', 'Wang, Xu', 'Wang, Yaoqin', 'Lutgendorf, Susan', 'Bradley, Catherine', 'Schrepf, Andrew', 'Kreder, Karl', ""O'Donnell, Michael"", 'Luo, Yi']",PLoS One,,,True
da215867201d36fa409a1f64aa89dfe75d537784,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,True
7d017d5285477ca084487a5fd8435fd64a59cce6,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,False
543059615137f6168bc68b4e7b5989f368a45a88,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,False
07567f87e6aace24f9146427f637ffba089ae28e,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,False
9a70adddbedf930be6c69a07b7c652240434f7ac,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,False
55c20a9eec895b673ce0751374bc9e725739101a,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,False
ca5f961909d1bf4d26815debd83d11f84b2c52d2,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,False
306ae95aab18fe16957a74a8681ed32130c052f4,PMC,A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus,http://dx.doi.org/10.1371/journal.pntd.0004953,PMC5042537,27685649,CC BY,"BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. CONCLUSIONS/SIGNIFICANCE: The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need.",2016 Sep 29,"['Patel, Pranav', 'Abd El Wahed, Ahmed', 'Faye, Oumar', 'Prüger, Pauline', 'Kaiser, Marco', 'Thaloengsok, Sasikanya', 'Ubol, Sukathida', 'Sakuntabhai, Anavaj', 'Leparc-Goffart, Isabelle', 'Hufert, Frank T.', 'Sall, Amadou A.', 'Weidmann, Manfred', 'Niedrig, Matthias']",PLoS Negl Trop Dis,,,False
5a6330a739f18fd6bc502bd9b59de55e8c081d4e,PMC,"ESICM LIVES 2016: part one: Milan, Italy. 1-5 October 2016",http://dx.doi.org/10.1186/s40635-016-0098-x,PMC5042924,,CC BY,,2016 Sep 29,"['Bos, L.', 'Schouten, L.', 'van Vught, L.', 'Wiewel, M.', 'Ong, D.', 'Cremer, O.', 'Artigas, A.', 'Martin-Loeches, I.', 'Hoogendijk, A.', 'van der Poll, T.', 'Horn, J.', 'Juffermans, N.', 'Schultz, M.', 'de Prost, N.', 'Pham, T.', 'Carteaux, G.', 'Dessap, A. Mekontso', 'Brun-Buisson, C.', 'Fan, E.', 'Bellani, G.', 'Laffey, J.', 'Mercat, A.', 'Brochard, L.', 'Maitre, B.', None, 'Howells, P. A.', 'Thickett, D. R.', 'Knox, C.', 'Park, D. P.', 'Gao, F.', 'Tucker, O.', 'Whitehouse, T.', 'McAuley, D. F.', 'Perkins, G. D.', 'Pham, T.', 'Laffey, J.', 'Bellani, G.', 'Fan, E.', None, 'Pisani, L.', 'Roozeman, J. P.', 'Simonis, F. D.', 'Giangregorio, A.', 'Schouten, L. R.', 'Van der Hoeven, S. M.', 'Horn, J.', 'Neto, A. Serpa', 'Festic, E.', 'Dondorp, A. M.', 'Grasso, S.', 'Bos, L. D.', 'Schultz, M. J.', 'Koster-Brouwer, M.', 'Verboom, D.', 'Scicluna, B.', 'van de Groep, K.', 'Frencken, J.', 'Schultz, M.', 'van der Poll, T.', 'Bonten, M.', 'Cremer, O.', 'Ko, J. I.', 'Kim, K. S.', 'Suh, G. J.', 'Kwon, W. Y.', 'Kim, K.', 'Shin, J. H.', 'Ranzani, O. T.', 'Prina, E.', 'Menendez, R.', 'Ceccato, A.', 'Mendez, R.', 'Cilloniz, C.', 'Gabarrus, A.', 'Ferrer, M.', 'Torres, A.', 'Urbano, A.', 'Zhang, L. A.', 'Swigon, D.', 'Pike, F.', 'Parker, R. S.', 'Clermont, G.', 'Scheer, C.', 'Kuhn, S. O.', 'Modler, A.', 'Vollmer, M.', 'Fuchs, C.', 'Hahnenkamp, K.', 'Rehberg, S.', 'Gründling, M.', 'Taggu, A.', 'Darang, N.', 'Öveges, N.', 'László, I.', 'Tánczos, K.', 'Németh, M.', 'Lebák, G.', 'Tudor, B.', 'Érces, D.', 'Kaszaki, J.', 'Huber, W.', 'Trásy, D.', 'Molnár, Z.', 'Ferrara, G.', 'Edul, V. S. Kanoore', 'Canales, H. S.', 'Martins, E.', 'Canullán, C.', 'Murias, G.', 'Pozo, M. O.', 'Eguillor, J. F. Caminos', 'Buscetti, M. G.', 'Ince, C.', 'Dubin, A.', 'Aya, H. D.', 'Rhodes, A.', 'Fletcher, N.', 'Grounds, R. M.', 'Cecconi, M.', 'Jacquet-Lagrèze, M.', 'Riche, M.', 'Schweizer, R.', 'Portran, P.', 'Fornier, W.', 'Lilot, M.', 'Neidecker, J.', 'Fellahi, J. L.', 'Escoresca-Ortega, A.', 'Gutiérrez-Pizarraya, A.', 'Charris-Castro, L.', 'Corcia-Palomo, Y.', 'Fernandez-Delgado, E.', 'Garnacho-Montero, J.', 'Roger, C.', 'Muller, L.', 'Elotmani, L.', 'Lipman, J.', 'Lefrant, J. Y.', 'Roberts, J. A.', 'Muñoz-Bermúdez, R.', 'Samper, M.', 'Climent, C.', 'Vasco, F.', 'Sara, V.', 'Luque, S.', 'Campillo, N.', 'Cerrato, S. Grau', 'Masclans, J. R.', 'Alvarez-Lerma, F.', 'Brugger, S. Carvalho', 'Jimenez, G. Jimenez', 'Torner, M. Miralbés', 'Cabello, J. Trujillano', 'Garrido, B. Balsera', 'Casals, X. Nuvials', 'Gaite, F. Barcenilla', 'Vidal, M. Vallverdú', 'Martínez, M. Palomar', 'Gusarov, V.', 'Shilkin, D.', 'Dementienko, M.', 'Nesterova, E.', 'Lashenkova, N.', 'Kuzovlev, A.', 'Zamyatin, M.', 'Demoule, A.', 'Carreira, S.', 'Lavault, S.', 'Palancca, O.', 'Morawiec, E.', 'Mayaux, J.', 'Arnulf, I.', 'Similowski, T.', 'Rasmussen, B. S.', 'Maltesen, R. G.', 'Hanifa, M.', 'Pedersen, S.', 'Kristensen, S. R.', 'Wimmer, R.', 'Panigada, M.', 'Bassi, G. Li', 'Ranzani, O. T.', 'Kolobow, T.', 'Zanella, A.', 'Cressoni, M.', 'Berra, L.', 'Parrini, V.', 'Kandil, H.', 'Salati, G.', 'Livigni, S.', 'Amatu, A.', 'Andreotti, A.', 'Tagliaferri, F.', 'Moise, G.', 'Mercurio, G.', 'Costa, A.', 'Vezzani, A.', 'Lindau, S.', 'Babel, J.', 'Cavana, M.', 'Consonni, D.', 'Pesenti, A.', 'Gattinoni, L.', 'Torres, A.', None, 'Mansouri, P.', 'Zand, F.', 'Zahed, L.', 'Dehghanrad, F.', 'Bahrani, M.', 'Ghorbani, M.', 'Cambiaghi, B.', 'Moerer, O.', 'Mauri, T.', 'Kunze-Szikszay, N.', 'Ritter, C.', 'Pesenti, A.', 'Quintel, M.', 'Vilander, L. M.', 'Kaunisto, M. A.', 'Vaara, S. T.', 'Pettilä, V.', None, 'Mulier, J. L. G. Haitsma', 'Rozemeijer, S.', 'Spoelstra-de Man, A. M. E.', 'Elbers, P. E.', 'Tuinman, P. R.', 'de Waard, M. C.', 'Oudemans-van Straaten, H. M.', 'Liberatore, A. M. A.', 'Souza, R. B.', 'Martins, A. M. C. R. P. F.', 'Vieira, J. C. F.', 'Koh, I. H. J.', 'Martínez, M. Galindo', 'Sánchez, R. Jiménez', 'Gascón, L. Martínez', 'Mulero, M. D. Rodríguez', 'Freire, A. Ortín', 'Muñoz, A. Ojados', 'Acebes, S. Rebollo', 'Martínez, Á. Fernández', 'Aliaga, S. Moreno', 'Para, L. Herrera', 'Payá, J. Murcia', 'Mulero, F. Rodríguez', 'Guerci, P.', 'Ince, Y.', 'Heeman, P.', 'Ergin, B.', 'Ince, C.', 'Uz, Z.', 'Massey, M.', 'Ince, Y.', 'Papatella, R.', 'Bulent, E.', 'Guerci, P.', 'Toraman, F.', 'Ince, C.', 'Longbottom, E. R.', 'Torrance, H. D.', 'Owen, H. C.', 'Hinds, C. J.', 'Pearse, R. M.', 'O’Dywer, M. J.', 'Trogrlic, Z.', 'van der Jagt, M.', 'Lingsma, H.', 'Ponssen, H. H.', 'Schoonderbeek, J. F.', 'Schreiner, F.', 'Verbrugge, S. J.', 'Duran, S.', 'van Achterberg, T.', 'Bakker, J.', 'Gommers, D. A. M. P. J.', 'Ista, E.', 'Krajčová, A.', 'Waldauf, P.', 'Duška, F.', 'Shah, A.', 'Roy, N.', 'McKechnie, S.', 'Doree, C.', 'Fisher, S.', 'Stanworth, S. J.', 'Jensen, J. F.', 'Overgaard, D.', 'Bestle, M. H.', 'Christensen, D. F.', 'Egerod, I.', None, 'Pivkina, A.', 'Gusarov, V.', 'Zhivotneva, I.', 'Pasko, N.', 'Zamyatin, M.', 'Jensen, J. F.', 'Egerod, I.', 'Bestle, M. H.', 'Christensen, D. F.', 'Alklit, A.', 'Hansen, R. L.', 'Knudsen, H.', 'Grode, L. B.', 'Overgaard, D.', None, 'Hravnak, M.', 'Chen, L.', 'Dubrawski, A.', 'Clermont, G.', 'Pinsky, M. R.', 'Parry, S. M.', 'Knight, L. D.', 'Connolly, B. C.', 'Baldwin, C. E.', 'Puthucheary, Z. A.', 'Denehy, L.', 'Hart, N.', 'Morris, P. E.', 'Mortimore, J.', 'Granger, C. L.', 'Jensen, H. I.', 'Piers, R.', 'Van den Bulcke, B.', 'Malmgren, J.', 'Metaxa, V.', 'Reyners, A. K.', 'Darmon, M.', 'Rusinova, K.', 'Talmor, D.', 'Meert, A. P.', 'Cancelliere, L.', 'Zubek, L.', 'Maia, P.', 'Michalsen, A.', 'Decruyenaere, J.', 'Kompanje, E.', 'Vanheule, S.', 'Azoulay, E.', 'Vansteelandt, S.', 'Benoit, D.', 'Van den Bulcke, B.', 'Piers, R.', 'Jensen, H. I.', 'Malmgren, J.', 'Metaxa, V.', 'Reyners, A. K.', 'Darmon, M.', 'Rusinova, K.', 'Talmor, D.', 'Meert, A. P.', 'Cancelliere, L.', 'Zubek, L.', 'Maia, P.', 'Michalsen, A.', 'Decruyenaere, J.', 'Kompanje, E.', 'Vanheule, S.', 'Azoulay, E.', 'Vansteelandt, S.', 'Benoit, D.', 'Ryan, C.', 'Dawson, D.', 'Ball, J.', 'Noone, K.', 'Aisling, B.', 'Prudden, S.', 'Ntantana, A.', 'Matamis, D.', 'Savvidou, S.', 'Giannakou, M.', 'Gouva, M.', 'Nakos, G.', 'Koulouras, V.', 'Aron, J.', 'Lumley, G.', 'Milliken, D.', 'Dhadwal, K.', 'McGrath, B. A.', 'Lynch, S. J.', 'Bovento, B.', 'Sharpe, G.', 'Grainger, E.', 'Pieri-Davies, S.', 'Wallace, S.', 'McGrath, B.', 'Lynch, S. J.', 'Bovento, B.', 'Grainger, E.', 'Pieri-Davies, S.', 'Sharpe, G.', 'Wallace, S.', 'Jung, M.', 'Cho, J.', 'Park, H.', 'Suh, G.', 'Kousha, O.', 'Paddle, J.', 'Gripenberg, L. Gamrin', 'Rehal, M. Sundström', 'Wernerman, J.', 'Rooyackers, O.', 'de Grooth, H. J.', 'Choo, W. P.', 'Spoelstra-de Man, A. M.', 'Swart, E. L.', 'Oudemans-van Straaten, H. M.', 'Talan, L.', 'Güven, G.', 'Altıntas, N. D.', 'Padar, M.', 'Uusvel, G.', 'Starkopf, L.', 'Starkopf, J.', 'Blaser, A. Reintam', 'Kalaiselvan, M. S.', 'Arunkumar, A. S.', 'Renuka, M. K.', 'Shivkumar, R. L.', 'Volbeda, M.', 'ten Kate, D.', 'Hoekstra, M.', 'van der Maaten, J. M.', 'Nijsten, M. W.', 'Komaromi, A.', 'Rooyackers, O.', 'Wernerman, J.', 'Norberg, Å.', 'Smedberg, M.', 'Mori, M.', 'Pettersson, L.', 'Norberg, Å.', 'Rooyackers, O.', 'Wernerman, J.', 'Theodorakopoulou, M.', 'Christodoulopoulou, T.', 'Diamantakis, A.', 'Frantzeskaki, F.', 'Kontogiorgi, M.', 'Chrysanthopoulou, E.', 'Lygnos, M.', 'Diakaki, C.', 'Armaganidis, A.', 'Gundogan, K.', 'Dogan, E.', 'Coskun, R.', 'Muhtaroglu, S.', 'Sungur, M.', 'Ziegler, T.', 'Guven, M.', 'Kleyman, A.', 'Khaliq, W.', 'Andreas, D.', 'Singer, M.', 'Meierhans, R.', 'Schuepbach, R.', 'De Brito-Ashurst, I.', 'Zand, F.', 'Sabetian, G.', 'Nikandish, R.', 'Hagar, F.', 'Masjedi, M.', 'Maghsudi, B.', 'Vazin, A.', 'Ghorbani, M.', 'Asadpour, E.', 'Kao, K. C.', 'Chiu, L. C.', 'Hung, C. Y.', 'Chang, C. H.', 'Li, S. H.', 'Hu, H. C.', 'El Maraghi, S.', 'Ali, M.', 'Rageb, D.', 'Helmy, M.', 'Marin-Corral, J.', 'Vilà, C.', 'Masclans, J. R.', 'Vàzquez, A.', 'Martín-Loeches, I.', 'Díaz, E.', 'Yébenes, J. C.', 'Rodriguez, A.', 'Álvarez-Lerma, F.', None, 'Varga, N.', 'Cortina-Gutiérrez, A.', 'Dono, L.', 'Martínez-Martínez, M.', 'Maldonado, C.', 'Papiol, E.', 'Pérez-Carrasco, M.', 'Ferrer, R.', 'Nweze, K.', 'Morton, B.', 'Welters, I.', 'Houard, M.', 'Voisin, B.', 'Ledoux, G.', 'Six, S.', 'Jaillette, E.', 'Nseir, S.', 'Romdhani, S.', 'Bouneb, R.', 'Loghmari, D.', 'Aicha, N. Ben', 'Ayachi, J.', 'Meddeb, K.', 'Chouchène, I.', 'Khedher, A.', 'Boussarsar, M.', 'Chan, K. S.', 'Yu, W. L.', 'Marin-Corral, J.', 'Vilà, C.', 'Masclans, J. R.', 'Nolla, J.', 'Vidaur, L.', 'Bonastre, J.', 'Suberbiola, B.', 'Guerrero, J. E.', 'Rodriguez, A.', None, 'Coll, N. Ramon', 'Jiménez, G. Jiménez', 'Brugger, S. Carvalho', 'Calero, J. Codina', 'Garrido, B. Balsera', 'García, M.', 'Martínez, M. Palomar', 'Vidal, M. Vallverdú', 'de la Torre, M. C.', 'Vendrell, E.', 'Palomera, E.', 'Güell, E.', 'Yébenes, J. C.', 'Serra-Prat, M.', 'Bermejo-Martín, J. F.', 'Almirall, J.', 'Tomas, E.', 'Escoval, A.', 'Froe, F.', 'Pereira, M. H. Vitoria', 'Velez, N.', 'Viegas, E.', 'Filipe, E.', 'Groves, C.', 'Reay, M.', 'Chiu, L. C.', 'Hu, H. C.', 'Hung, C. Y.', 'Chang, C. H.', 'Li, S. H.', 'Kao, K. C.', 'Ballin, A.', 'Facchin, F.', 'Sartori, G.', 'Zarantonello, F.', 'Campello, E.', 'Radu, C. M.', 'Rossi, S.', 'Ori, C.', 'Simioni, P.', 'Umei, N.', 'Shingo, I.', 'Santos, A. C.', 'Candeias, C.', 'Moniz, I.', 'Marçal, R.', 'e Silva, Z. Costa', 'Ribeiro, J. M.', 'Georger, J. F.', 'Ponthus, J. P.', 'Tchir, M.', 'Amilien, V.', 'Ayoub, M.', 'Barsam, E.', 'Martucci, G.', 'Panarello, G.', 'Tuzzolino, F.', 'Capitanio, G.', 'Ferrazza, V.', 'Carollo, T.', 'Giovanni, L.', 'Arcadipane, A.', 'Sánchez, M. López', 'González-Gay, M. A.', 'Díaz, F. J. Llorca', 'López, M. I. Rubio', 'Zogheib, E.', 'Villeret, L.', 'Nader, J.', 'Bernasinski, M.', 'Besserve, P.', 'Caus, T.', 'Dupont, H.', 'Morimont, P.', 'Habran, S.', 'Hubert, R.', 'Desaive, T.', 'Blaffart, F.', 'Janssen, N.', 'Guiot, J.', 'Pironet, A.', 'Dauby, P.', 'Lambermont, B.', 'Zarantonello, F.', 'Ballin, A.', 'Facchin, F.', 'Sartori, G.', 'Campello, E.', 'Pettenuzzo, T.', 'Citton, G.', 'Rossi, S.', 'Simioni, P.', 'Ori, C.', 'Kirakli, C.', 'Ediboglu, O.', 'Ataman, S.', 'Yarici, M.', 'Tuksavul, F.', 'Keating, S.', 'Gibson, A.', 'Gilles, M.', 'Dunn, M.', 'Price, G.', 'Young, N.', 'Remeta, P.', 'Bishop, P.', 'Zamora, M. D. Fernández', 'Muñoz-Bono, J.', 'Curiel-Balsera, E.', 'Aguilar-Alonso, E.', 'Hinojosa, R.', 'Gordillo-Brenes, A.', 'Arboleda-Sánchez, J. A.', None, 'Skorniakov, I.', 'Vikulova, D.', 'Whiteley, C.', 'Shaikh, O.', 'Jones, A.', 'Ostermann, M.', 'Forni, L.', 'Scott, M.', 'Sahatjian, J.', 'Linde-Zwirble, W.', 'Hansell, D.', 'Laoveeravat, P.', 'Srisawat, N.', 'Kongwibulwut, M.', 'Peerapornrattana, S.', 'Suwachittanont, N.', 'Wirotwan, T. O.', 'Chatkaew, P.', 'Saeyub, P.', 'Latthaprecha, K.', 'Tiranathanagul, K.', 'Eiam-ong, S.', 'Kellum, J. A.', 'Berthelsen, R. E.', 'Perner, A.', 'Jensen, A. E. K.', 'Jensen, J. U.', 'Bestle, M. H.', 'Gebhard, D. J.', 'Price, J.', 'Kennedy, C. E.', 'Akcan-Arikan, A.', 'Liberatore, A. M. A.', 'Souza, R. B.', 'Martins, A. M. C. R. P. F.', 'Vieira, J. C. F.', 'Kang, Y. R.', 'Nakamae, M. N.', 'Koh, I. H. J.', 'Hamed, K.', 'Khaled, M. M.', 'Soliman, R. Aly', 'Mokhtar, M. Sherif', 'Seller-Pérez, G.', 'Arias-Verdú, D.', 'Llopar-Valdor, E.', 'De-Diós-Chacón, I.', 'Quesada-García, G.', 'Herrera-Gutierrez, M. E.', 'Hafes, R.', 'Carroll, G.', 'Doherty, P.', 'Wright, C.', 'Vera, I. G. Guerra', 'Ralston, M.', 'Gemmell, M. L.', 'MacKay, A.', 'Black, E.', 'Wright, C.', 'Docking, R. I.', 'Appleton, R.', 'Ralston, M. R.', 'Gemmell, L.', 'Appleton, R.', 'Wright, C.', 'Docking, R. I.', 'Black, E.', 'Mackay, A.', 'Rozemeijer, S.', 'Mulier, J. L. G. Haitsma', 'Röttgering, J. G.', 'Elbers, P. W. G.', 'Spoelstra-de Man, A. M. E.', 'Tuinman, P. R.', 'de Waard, M. C.', 'Oudemans-van Straaten, H. M.', 'Mejeni, N.', 'Nsiala, J.', 'Kilembe, A.', 'Akilimali, P.', 'Thomas, G.', 'Egerod, I.', 'Andersson, A. E.', 'Fagerdahl, A. M.', 'Knudsen, V.', None, 'Meddeb, K.', 'Cheikh, A. Ben', 'Hamdaoui, Y.', 'Ayachi, J.', 'Guiga, A.', 'Fraj, N.', 'Romdhani, S.', 'Sma, N.', 'Bouneb, R.', 'Chouchene, I.', 'Khedher, A.', 'Bouafia, N.', 'Boussarsar, M.', 'Amirian, A.', 'Ziaian, B.', 'Masjedi, M.', 'Fleischmann, C.', 'Thomas-Rueddel, D. O.', 'Schettler, A.', 'Schwarzkopf, D.', 'Stacke, A.', 'Reinhart, K.', 'Filipe, E.', 'Escoval, A.', 'Martins, A.', 'Sousa, P.', 'Velez, N.', 'Viegas, E.', 'Tomas, E.', 'Snell, G.', 'Matsa, R.', 'Paary, T. T. S.', 'Kalaiselvan, M. S.', 'Cavalheiro, A. M.', 'Rocha, L. L.', 'Vallone, C. S.', 'Tonilo, A.', 'Lobato, M. D. S.', 'Malheiro, D. T.', 'Sussumo, G.', 'Lucino, N. M.', 'Zand, F.', 'Rosenthal, V. D.', 'Masjedi, M.', 'Sabetian, G.', 'Maghsudi, B.', 'Ghorbani, M.', 'Dashti, A. Sanaei', 'Yousefipour, A.', 'Goodall, J. R.', 'Williamson, M.', 'Tant, E.', 'Thomas, N.', 'Balci, C.', 'Gonen, C.', 'Haftacı, E.', 'Gurarda, H.', 'Karaca, E.', 'Paldusová, B.', 'Zýková, I.', 'Šímová, D.', 'Houston, S.', 'D’Antona, L.', 'Lloyd, J.', 'Garnelo-Rey, V.', 'Sosic, M.', 'Sotosek-Tokmazic, V.', 'Kuharic, J.', 'Antoncic, I.', 'Dunatov, S.', 'Sustic, A.', 'Chong, C. T.', 'Sim, M.', 'Lyovarin, T.', 'Díaz, F. M. Acosta', 'Galdó, S. Narbona', 'Garach, M. Muñoz', 'Romero, O. Moreno', 'Bailón, A. M. Pérez', 'Pinel, A. Carranza', 'Colmenero, M.', 'Gritsan, A.', 'Gazenkampf, A.', 'Korchagin, E.', 'Dovbish, N.', 'Lee, R. M.', 'Lim, M. P. P.', 'Chong, C. T.', 'Lim, B. C. L.', 'See, J. J.', 'Assis, R.', 'Filipe, F.', 'Lopes, N.', 'Pessoa, L.', 'Pereira, T.', 'Catorze, N.', 'Aydogan, M. S.', 'Aldasoro, C.', 'Marchio, P.', 'Jorda, A.', 'Mauricio, M. D.', 'Guerra-Ojeda, S.', 'Gimeno-Raga, M.', 'Colque-Cano, M.', 'Bertomeu-Artecero, A.', 'Aldasoro, M.', 'Valles, S. L.', 'Tonon, D.', 'Triglia, T.', 'Martin, J. C.', 'Alessi, M. C.', 'Bruder, N.', 'Garrigue, P.', 'Velly, L.', 'Spina, S.', 'Scaravilli, V.', 'Marzorati, C.', 'Colombo, E.', 'Savo, D.', 'Vargiolu, A.', 'Cavenaghi, G.', 'Citerio, G.', 'Andrade, A. H. V.', 'Bulgarelli, P.', 'Araujo, J. A. P.', 'Gonzalez, V.', 'Souza, V. A.', 'Costa, A.', 'Massant, C.', 'Filho, C. A. C. Abreu', 'Morbeck, R. A.', 'Burgo, L. E.', 'van Groenendael, R.', 'van Eijk, L. T.', 'Leijte, G. P.', 'Koeneman, B.', 'Kox, M.', 'Pickkers, P.', 'García-de la Torre, A.', 'de la Torre-Prados, M.', 'Fernández-Porcel, A.', 'Rueda-Molina, C.', 'Nuevo-Ortega, P.', 'Tsvetanova-Spasova, T.', 'Cámara-Sola, E.', 'García-Alcántara, A.', 'Salido-Díaz, L.', 'Liao, X.', 'Feng, T.', 'Zhang, J.', 'Cao, X.', 'Wu, Q.', 'Xie, Z.', 'Li, H.', 'Kang, Y.', 'Winkler, M. S.', 'Nierhaus, A.', 'Mudersbach, E.', 'Bauer, A.', 'Robbe, L.', 'Zahrte, C.', 'Schwedhelm, E.', 'Kluge, S.', 'Zöllner, C.', 'Morton, B.', 'Mitsi, E.', 'Pennington, S. H.', 'Reine, J.', 'Wright, A. D.', 'Parker, R.', 'Welters, I. D.', 'Blakey, J. D.', 'Rajam, G.', 'Ades, E. W.', 'Ferreira, D. M.', 'Wang, D.', 'Kadioglu, A.', 'Gordon, S. B.', 'Koch, R.', 'Kox, M.', 'Rahamat-Langedoen, J.', 'Schloesser, J.', 'de Jonge, M.', 'Pickkers, P.', 'Bringue, J.', 'Guillamat-Prats, R.', 'Torrents, E.', 'Martinez, M. L.', 'Camprubí-Rimblas, M.', 'Artigas, A.', 'Blanch, L.', 'Park, S. Y.', 'Park, Y. B.', 'Song, D. K.', 'Shrestha, S.', 'Park, S. H.', 'Koh, Y.', 'Park, M. J.', 'Hong, C. W.', 'Lesur, O.', 'Coquerel, D.', 'Sainsily, X.', 'Cote, J.', 'Söllradl, T.', 'Murza, A.', 'Dumont, L.', 'Dumaine, R.', 'Grandbois, M.', 'Sarret, P.', 'Marsault, E.', 'Salvail, D.', 'Auger-Messier, M.', 'Chagnon, F.', None, 'Lauretta, M. P.', 'Greco, E.', 'Dyson, A.', 'Singer, M.', 'Preau, S.', 'Ambler, M.', 'Sigurta, A.', 'Saeed, S.', 'Singer, M.', 'Sarıca, L. Topcu', 'Zibandeh, N.', 'Genc, D.', 'Gul, F.', 'Akkoc, T.', 'Kombak, E.', 'Cinel, L.', 'Akkoc, T.', 'Cinel, I.', 'Pollen, S. J.', 'Arulkumaran, N.', 'Singer, M.', 'Torrance, H. D.', 'Longbottom, E. R.', 'Warnes, G.', 'Hinds, C. J.', 'Pennington, D. J.', 'Brohi, K.', 'O’Dwyer, M. J.', 'Kim, H. Y.', 'Na, S.', 'Kim, J.', 'Chang, Y. F.', 'Chao, A.', 'Shih, P. Y.', 'Lee, C. T.', 'Yeh, Y. C.', 'Chen, L. W.', 'Adriaanse, M.', 'Trogrlic, Z.', 'Ista, E.', 'Lingsma, H.', 'Rietdijk, W.', 'Ponssen, H. H.', 'Schoonderbeek, J. F.', 'Schreiner, F.', 'Verbrugge, S. J.', 'Duran, S.', 'Gommers, D. A. M. P. J.', 'van der Jagt, M.', 'Funcke, S.', 'Sauerlaender, S.', 'Saugel, B.', 'Pinnschmidt, H.', 'Reuter, D. A.', 'Nitzschke, R.', 'Perbet, S.', 'Biboulet, C.', 'Lenoire, A.', 'Bourdeaux, D.', 'Pereira, B.', 'Plaud, B.', 'Bazin, J. E.', 'Sautou, V.', 'Mebazaa, A.', 'Constantin, J. M.', 'Legrand, M.', 'Boyko, Y.', 'Jennum, P.', 'Nikolic, M.', 'Oerding, H.', 'Holst, R.', 'Toft, P.', 'Nedergaard, H. K.', 'Haberlandt, T.', 'Jensen, H. I.', 'Toft, P.', 'Park, S.', 'Kim, S.', 'Cho, Y. J.', 'Lim, Y. J.', 'Chan, A.', 'Tang, S.', 'Nunes, S. L.', 'Forsberg, S.', 'Blomqvist, H.', 'Berggren, L.', 'Sörberg, M.', 'Sarapohja, T.', 'Wickerts, C. J.', 'Hofhuis, J. G. M.', 'Rose, L.', 'Blackwood, B.', 'Akerman, E.', 'Mcgaughey, J.', 'Egerod, I.', 'Fossum, M.', 'Foss, H.', 'Georgiou, E.', 'Graff, H. J.', 'Kalafati, M.', 'Sperlinga, R.', 'Schafer, A.', 'Wojnicka, A. G.', 'Spronk, P. E.', 'Zand, F.', 'Khalili, F.', 'Afshari, R.', 'Sabetian, G.', 'Masjedi, M.', 'Maghsudi, B.', 'Khodaei, H. Haddad', 'Javadpour, S.', 'Petramfar, P.', 'Nasimi, S.', 'Vazin, A.', 'Ziaian, B.', 'Tabei, H.', 'Gunther, A.', 'Hansen, J. O.', 'Sackey, P.', 'Storm, H.', 'Bernhardsson, J.', 'Sundin, Ø.', 'Bjärtå, A.', 'Bienert, A.', 'Smuszkiewicz, P.', 'Wiczling, P.', 'Przybylowski, K.', 'Borsuk, A.', 'Trojanowska, I.', 'Matysiak, J.', 'Kokot, Z.', 'Paterska, M.', 'Grzeskowiak, E.', 'Messina, A.', 'Bonicolini, E.', 'Colombo, D.', 'Moro, G.', 'Romagnoli, S.', 'De Gaudio, A. R.', 'Corte, F. Della', 'Romano, S. M.', 'Silversides, J. A.', 'Major, E.', 'Mann, E. E.', 'Ferguson, A. J.', 'Mcauley, D. F.', 'Marshall, J. C.', 'Blackwood, B.', 'Fan, E.', 'Diaz-Rodriguez, J. A.', 'Silva-Medina, R.', 'Gomez-Sandoval, E.', 'Gomez-Gonzalez, N.', 'Soriano-Orozco, R.', 'Gonzalez-Carrillo, P. L.', 'Hernández-Flores, M.', 'Pilarczyk, K.', 'Lubarksi, J.', 'Wendt, D.', 'Dusse, F.', 'Günter, J.', 'Huschens, B.', 'Demircioglu, E.', 'Jakob, H.', 'Palmaccio, A.', 'Dell’Anna, A. M.', 'Grieco, D. L.', 'Torrini, F.', 'Iaquaniello, C.', 'Bongiovanni, F.', 'Antonelli, M.', 'Toscani, L.', 'Antonakaki, D.', 'Bastoni, D.', 'Aya, H. D.', 'Rhodes, A.', 'Cecconi, M.', 'Jozwiak, M.', 'Depret, F.', 'Teboul, J. L.', 'Alphonsine, J.', 'Lai, C.', 'Richard, C.', 'Monnet, X.', 'László, I.', 'Demeter, G.', 'Öveges, N.', 'Tánczos, K.', 'Németh, M.', 'Trásy, D.', 'Kertmegi, I.', 'Érces, D.', 'Tudor, B.', 'Kaszaki, J.', 'Molnár, Z.', 'Hasanin, A.', 'Lotfy, A.', 'El-adawy, A.', 'Nassar, H.', 'Mahmoud, S.', 'Abougabal, A.', 'Mukhtar, A.', 'Quinty, F.', 'Habchi, S.', 'Luzi, A.', 'Antok, E.', 'Hernandez, G.', 'Lara, B.', 'Enberg, L.', 'Ortega, M.', 'Leon, P.', 'Kripper, C.', 'Aguilera, P.', 'Kattan, E.', 'Bakker, J.', 'Huber, W.', 'Lehmann, M.', 'Sakka, S.', 'Bein, B.', 'Schmid, R. M.', 'Preti, J.', 'Creteur, J.', 'Herpain, A.', 'Marc, J.', 'Zogheib, E.', 'Trojette, F.', 'Bar, S.', 'Kontar, L.', 'Titeca, D.', 'Richecoeur, J.', 'Gelee, B.', 'Verrier, N.', 'Mercier, R.', 'Lorne, E.', 'Maizel, J.', 'Dupont, H.', 'Slama, M.', 'Abdelfattah, M. E.', 'Eladawy, A.', 'Elsayed, M. A. Ali', 'Mukhtar, A.', 'Montenegro, A. Pedraza', 'Zepeda, E. Monares', 'Granillo, J. Franco', 'Sánchez, J. S. Aguirre', 'Alejo, G. Camarena', 'Cabrera, A. Rugerio', 'Montoya, A. A. Tanaka', 'Lee, C.', 'Hatib, F.', 'Cannesson, M.', 'Theerawit, P.', 'Morasert, T.', 'Sutherasan, Y.', 'Zani, G.', 'Mescolini, S.', 'Diamanti, M.', 'Righetti, R.', 'Scaramuzza, A.', 'Papetti, M.', 'Terenzoni, M.', 'Gecele, C.', 'Fusari, M.', 'Hakim, K. A.', 'Chaari, A.', 'Ismail, M.', 'Elsaka, A. H.', 'Mahmoud, T. M.', 'Bousselmi, K.', 'Kauts, V.', 'Casey, W. F.', 'Hutchings, S. D.', 'Naumann, D.', 'Wendon, J.', 'Watts, S.', 'Kirkman, E.', 'Jian, Z.', 'Buddi, S.', 'Lee, C.', 'Settels, J.', 'Hatib, F.', 'Pinsky, M. R.', 'Bertini, P.', 'Guarracino, F.', 'Trepte, C.', 'Richter, P.', 'Haas, S. A.', 'Eichhorn, V.', 'Kubitz, J. C.', 'Reuter, D. A.', 'Soliman, M. S.', 'Hamimy, W. I.', 'Fouad, A. Z.', 'Mukhtar, A. M.', 'Charlton, M.', 'Tonks, L.', 'Mclelland, L.', 'Coats, T. J.', 'Thompson, J. P.', 'Sims, M. R.', 'Williams, D.', 'Roushdy, D. Z.', 'Soliman, R. A.', 'Nahas, R. A.', 'Arafa, M. Y.', 'Hung, W. T.', 'Chiang, C. C.', 'Huang, W. C.', 'Lin, K. C.', 'Lin, S. C.', 'Cheng, C. C.', 'Kang, P. L.', 'Wann, S. R.', 'Mar, G. Y.', 'Liu, C. P.', 'Carranza, M. Lopez', 'Fernandez, H. Sancho', 'Roman, J. A. Sanchez', 'Lucena, F.', 'Garcia, A. Campanario', 'Vazquez, A. Loza', 'Serrano, A. Lesmes', None, 'Moreira, L. Sayagues', 'Vidal-Perez, R.', 'Herranz, U. Anido', 'Acuna, J. M. Garcia', 'Gil, C. Pena', 'Allut, J. L. Garcia', 'Sedes, P. Rascado', 'Lopez, C. Martin', 'Paz, E. Saborido', 'Rodriguez, C. Galban', 'Gonzalez-Juanatey, J. R.', 'Vallejo-Baez, A.', 'de la Torre-Prados, M. V.', 'Nuevo-Ortega, P.', 'Fernández-Porcel, A.', 'Cámara-Sola, E.', 'Tsvetanova-Spasova, T.', 'Rueda-Molina, C.', 'Salido-Díaz, L.', 'García-Alcántara, A.', None, 'Aron, J.', 'Marharaj, R.', 'Gervasio, K.', 'Bottiroli, M.', 'Mondino, M.', 'De Caria, D.', 'Calini, A.', 'Montrasio, E.', 'Milazzo, F.', 'Gagliardone, M. P.', 'Vallejo-Báez, A.', 'de la Torre-Prados, M. V.', 'Nuevo-Ortega, P.', 'Fernández-Porcel, A.', 'Cámara-Sola, E.', 'Tsvetanova-Spasova, T.', 'Rueda-Molina, C.', 'Salido-Díaz, L.', 'García-Alcántara, A.', None, 'Moreira, L. Sayagues', 'Vidal-Perez, R.', 'Anido, U.', 'Gil, C. Pena', 'Acuna, J. M. Garcia', 'Sedes, P. Rascado', 'Lopez, C. Martin', 'Paz, E. Saborido', 'Allut, J. L. Garcia', 'Rodriguez, C. Galban', 'Gonzalez-Juanatey, J. R.', 'Hamdaoui, Y.', 'Khedher, A.', 'Cheikh-Bouhlel, M.', 'Ayachi, J.', 'Meddeb, K.', 'Sma, N.', 'Fraj, N.', 'Aicha, N. Ben', 'Romdhani, S.', 'Bouneb, R.', 'Chouchene, I.', 'Boussarsar, M.', 'Dela Cruz, M. P. R. D. L.', 'Bernardo, J. M.', 'Galfo, F.', 'Dyson, A.', 'Singer, M.', 'Marino, A.', 'Dyson, A.', 'Singer, M.', 'Chao, C. C.', 'Hou, P.', 'Huang, W. C.', 'Hung, C. C.', 'Chiang, C. H.', 'Hung, W. T.', 'Lin, K. C.', 'Lin, S. C.', 'Liou, Y. J.', 'Hung, S. M.', 'Lin, Y. S.', 'Cheng, C. C.', 'Kuo, F. Y.', 'Chiou, K. R.', 'Chen, C. J.', 'Yan, L. S.', 'Liu, C. Y.', 'Wang, H. H.', 'Kang, P. L.', 'Chen, H. L.', 'Ho, C. K.', 'Mar, G. Y.', 'Liu, C. P.', 'Grewal, S.', 'Gopal, S.', 'Corbett, C.', 'Wilson, A.', 'Capps, J.', 'Ayoub, W.', 'Lomas, A.', 'Ghani, S.', 'Moore, J.', 'Atkinson, D.', 'Sharman, M.', 'Swinnen, W.', 'Pauwels, J.', 'Mignolet, K.', 'Pannier, E.', 'Koch, A.', 'Sarens, T.', 'Temmerman, W.', 'Elmenshawy, A. M.', 'Fayed, A. M.', 'Elboriuny, M.', 'Hamdy, E.', 'Zakaria, E.', 'Falk, A. C.', 'Petosic, A.', 'Olafsen, K.', 'Wøien, H.', 'Flaatten, H.', 'Sunde, K.', 'Agra, J. J. Cáceres', 'Cabrera, J. L. Santana', 'Santana, J. D. Martín', 'Alzola, L. Melián', 'Pérez, H. Rodríguez', 'Pires, T. Castro', 'Calderón, H.', 'Pereira, A.', 'Castro, S.', 'Granja, C.', 'Norkiene, I.', 'Urbanaviciute, I.', 'Kezyte, G.', 'Ringaitiene, D.', 'Jovaisa, T.', 'Vogel, G.', 'Johansson, U. B.', 'Sandgren, A.', 'Svensen, C.', 'Joelsson-Alm, E.', 'Leite, M. A.', 'Murbach, L. D.', 'Osaku, E. F.', 'Costa, C. R. L. M.', 'Pelenz, M.', 'Neitzke, N. M.', 'Moraes, M. M.', 'Jaskowiak, J. L.', 'Silva, M. M. M.', 'Zaponi, R. S.', 'Abentroth, L. R. L.', 'Ogasawara, S. M.', 'Jorge, A. C.', 'Duarte, P. A. D.', 'Murbach, L. D.', 'Leite, M. A.', 'Osaku, E. F.', 'Barreto, J.', 'Duarte, S. T.', 'Taba, S.', 'Miglioranza, D.', 'Gund, D. P.', 'Lordani, C. F.', 'Costa, C. R. L. M.', 'Ogasawara, S. M.', 'Jorge, A. C.', 'Duarte, P. A. D.', 'Vollmer, H.', 'Gager, M.', 'Waldmann, C.', 'Mazzeo, A. T.', 'Tesio, R.', 'Filippini, C.', 'Vallero, M. E.', 'Giolitti, C.', 'Caccia, S.', 'Medugno, M.', 'Tenaglia, T.', 'Rosato, R.', 'Mastromauro, I.', 'Brazzi, L.', 'Terragni, P. P.', 'Urbino, R.', 'Fanelli, V.', 'Ranieri, V. M.', 'Mascia, L.', 'Ballantyne, J.', 'Paton, L.', 'Mackay, A.', 'Perez-Teran, P.', 'Roca, O.', 'Ruiz-Rodriguez, J. C.', 'Zapatero, A.', 'Serra, J.', 'Masclans, J. R.', 'Bianzina, S.', 'Cornara, P.', 'Rodi, G.', 'Tavazzi, G.', 'Pozzi, M.', 'Iotti, G. A.', 'Mojoli, F.', 'Braschi, A.', 'Vishnu, A.', 'Buche, D.', 'Pande, R.', 'Moolenaar, D. L. J.', 'Bakhshi-Raiez, F.', 'Dongelmans, D. A.', 'de Keizer, N. F.', 'de Lange, D. W.', 'Fernández, I. Fuentes', 'Baño, D. Martínez', 'Moreno, J. L. Buendía', 'Rubio, R. Jara', 'Scott, J.', 'Phelan, D.', 'Morely, D.', 'O’Flynn, J.', 'Stapleton, P.', 'Lynch, M.', 'Marsh, B.', 'Carton, E.', 'O’Loughlin, C.', 'Cheng, K. C.', 'Sung, M. I.', 'Elghonemi, M. O.', 'Saleh, M. H.', 'Meyhoff, T. S.', 'Krag, M.', 'Hjortrup, P. B.', 'Perner, A.', 'Møller, M. H.', 'Öhman, T.', 'Sigmundsson, T.', 'Redondo, E.', 'Hallbäck, M.', 'Suarez-Sipmann, F.', 'Björne, H.', 'Sander, C. Hällsjö', None, 'Cressoni, M.', 'Chiumello, D.', 'Chiurazzi, C.', 'Brioni, M.', 'Algieri, I.', 'Guanziroli, M.', 'Vergani, G.', 'Tonetti, T.', 'Tomic, I.', 'Colombo, A.', 'Crimella, F.', 'Carlesso, E.', 'Colombo, A.', 'Gasparovic, V.', 'Gattinoni, L.', 'El-Sherif, R.', 'Al-Basser, M. Abd', 'Raafat, A.', 'El-Sherif, A.', 'Simonis, F. D.', 'Schouten, L. R. A.', 'Cremer, O. L.', 'Ong, D. S. Y.', 'Amoruso, G.', 'Cinnella, G.', 'Schultz, M. J.', 'Bos, L. D. J.', 'Huber, W.', 'Schmidle, P.', 'Findeisen, M.', 'Hoppmann, P.', 'Jaitner, J.', 'Brettner, F.', 'Schmid, R. M.', 'Lahmer, T.', None, 'Festic, E.', 'Rajagopalan, G.', 'Bansal, V.', 'Frank, R.', 'Hinds, R.', 'Levitt, J.', None, 'Siddiqui, S.', None, 'Gilbert, J. P.', 'Sim, K.', 'Wang, C. H.', 'Hu, H. C.', 'Li, I. J.', 'Tang, W. R.', 'Kao, K. C.', 'Persona, P.', 'De Cassai, A.', 'Franco, M.', 'Facchin, F.', 'Ori, C.', 'Rossi, S.', 'Goffi, A.', 'Li, S. H.', 'Hu, H. C.', 'Chiu, L. C.', 'Hung, C. Y.', 'Chang, C. H.', 'Kao, K. C.', 'Ruiz, B. Llorente', 'Varas, J. Lujan', 'Montero, R. Molina', 'Delgado, C. Pintado', 'Navarrete, O.', 'Mezquita, M. Vazquez', 'Peces, E. Alonso', 'Nakamura, M. A. M.', 'Hajjar, L. A.', 'Galas, F. R. B. G.', 'Ortiz, T. A.', 'Amato, M. B. P.', 'Bitker, L.', 'Costes, N.', 'Le Bars, D.', 'Lavenne, F.', 'Mojgan, D.', 'Richard, J. C.', 'Chiurazzi, C.', 'Cressoni, M.', 'Massari, D.', 'Guanziroli, M.', 'Vergani, G.', 'Gotti, M.', 'Brioni, M.', 'Algieri, I.', 'Cadringher, P.', 'Tonetti, T.', 'Chiumello, D.', 'Gattinoni, L.', 'Zerman, A.', 'Türkoğlu, M.', 'Arık, G.', 'Yıldırım, F.', 'Güllü, Z.', 'Kara, I.', 'Boyacı, N.', 'Aydoğan, B. Basarık', 'Gaygısız, Ü.', 'Gönderen, K.', 'Aygencel, G.', 'Aydoğdu, M.', 'Ülger, Z.', 'Gürsel, G.', 'Riera, J.', 'Toral, C. Maldonado', 'Mazo, C.', 'Martínez, M.', 'Baldirà, J.', 'Lagunes, L.', 'Roman, A.', 'Deu, M.', 'Rello, J.', 'Levine, D. J.', 'Mohus, R. M.', 'Askim, Å.', 'Paulsen, J.', 'Mehl, A.', 'Dewan, A. T.', 'Damås, J. K.', 'Solligård, E.', 'Åsvold, B. O.', None, 'Paulsen, J.', 'Askim, Å.', 'Mohus, R. M.', 'Mehl, A.', 'DeWan, A.', 'Solligård, E.', 'Damås, J. K.', 'Åsvold, B. O.', 'Aktepe, O.', 'Kara, A.', 'Yeter, H.', 'Topeli, A.', 'Norrenberg, M.', 'Devroey, M.', 'Khader, H.', 'Preiser, J. C.', 'Tang, Z.', 'Qiu, C.', 'Tong, L.', 'Cai, C.', 'Theodorakopoulou, M.', 'Diamantakis, A.', 'Kontogiorgi, M.', 'Chrysanthopoulou, E.', 'Christodoulopoulou, T.', 'Frantzeskaki, F.', 'Lygnos, M.', 'Apostolopoulou, O.', 'Armaganidis, A.', 'Moon, J. Y.', 'Park, M. R.', 'Kwon, I. S.', 'Chon, G. R.', 'Ahn, J. Y.', 'Kwon, S. J.', 'Chang, Y. J.', 'Lee, J. Y.', 'Yoon, S. Y.', 'Lee, J. W.', None, 'Kostalas, M.', 'Mckinlay, J.', 'Kooner, G.', 'Dudas, G.', 'Horton, A.', 'Kerr, C.', 'Karanjia, N.', 'Creagh-Brown, B.', 'Altintas, N. D.', 'Izdes, S.', 'Keremoglu, O.', 'Alkan, A.', 'Neselioglu, S.', 'Erel, O.', 'Tardif, N.', 'Gustafsson, T.', 'Rooyackers, O.', 'MacEachern, K. N.', 'Traille, M.', 'Bromberg, I.', 'Lapinsky, S. E.', 'Moore, M. J.', 'Tang, Z.', 'Cai, C.', 'Tong, L.', 'García-Garmendia, J. L.', 'Villarrasa-Clemente, F.', 'Maroto-Monserrat, F.', 'Rufo-Tejeiro, O.', 'Jorge-Amigo, V.', 'Sánchez-Santamaría, M.', 'Colón-Pallarés, C.', 'Barrero-Almodóvar, A.', 'Gallego-Lara, S.', 'Anthon, C. T.', 'Müller, R. B.', 'Haase, N.', 'Møller, K.', 'Hjortrup, P. B.', 'Wetterslev, J.', 'Perner, A.', 'Nakanishi, M.', 'Kuriyama, A.', 'Fukuoka, T.', 'Abd el Halim, M. A.', 'Elsaid hafez, M. H.', 'Moktar, A. M.', 'Eladawy, A.', 'Elazizy, H. M.', 'Hakim, K. Abdel', 'Chaari, A.', 'Elbahr, M.', 'Ismail, M.', 'Mahmoud, T.', 'Kauts, V.', 'Bousselmi, K.', 'Khalil, E.', 'Casey, W.', 'Zaky, S. H.', 'Rizk, A.', 'Elghonemi, M. O.', 'Ahmed, R.', 'Vieira, J. C. F.', 'Souza, R. B.', 'Liberatore, A. M. A.', 'Koh, I. H. J.', 'Ospina-Tascón, G. A.', 'Marin, A. F. Garcia', 'Echeverry, G. J.', 'Bermudez, W. F.', 'Madriñan-Navia, H. J.', 'Valencia, J. D.', 'Quiñonez, E.', 'Marulanda, A.', 'Arango-Dávila, C. A.', 'Bruhn, A.', 'Hernandez, G.', 'De Backer, D.', 'Cortes, D. Orbegozo', 'Su, F.', 'Vincent, J. L.', 'Creteur, J.', 'Tullo, L.', 'Mirabella, L.', 'Di Molfetta, P.', 'Cinnella, G.', 'Dambrosio, M.', 'Lujan, C. Villavicencio', 'irigoyen, J. Leache', 'Cartanya ferré, M.', 'García, R. Carbonell', 'Mukhtar, A.', 'Ahmed, M.', 'El Ayashi, M.', 'Hasanin, A.', 'Ayman, E.', 'Salem, M.', 'Eladawy, A.', 'Fathy, S.', 'Nassar, H.', 'Zaghlol, A.', 'Arzapalo, M. F. Aguilar', 'Valsø, Å.', 'Sunde, K.', 'Rustøen, T.', 'Schou-Bredal, I.', 'Skogstad, L.', 'Tøien, K.', 'Padilla, C.', 'Palmeiro, Y.', 'Egbaria, W.', 'Kigli, R.', 'Maertens, B.', 'Blot, K.', 'Blot, S.', 'Santana-Santos, E.', 'dos Santos, E. R.', 'Ferretti-Rebustini, R. E. D. L.', 'dos Santos, R. D. C. C. D. O.', 'Verardino, R. G. S.', 'Bortolotto, L. A.', 'Doyle, A. M.', 'Naldrett, I.', 'Tillman, J.', 'Price, S.', 'Shrestha, S.', 'Pearson, P.', 'Greaves, J.', 'Goodall, D.', 'Berry, A.', 'Richardson, A.', 'Odundo, G. O.', 'Omengo, P.', 'Obonyo, P.', 'Chanzu, N. M.', 'Kleinpell, R.', 'Sarris, S. J.', 'Nedved, P.', 'Heitschmidt, M.', 'Ben-Ghezala, H.', 'Snouda, S.', 'Djobbi, S.', 'Ben-Ghezala, H.', 'Snouda, S.', 'Rose, L.', 'Adhikari, N. K. J.', 'Leasa, D.', 'Fergusson, D.', 'Mckim, D. A.', 'Weblin, J.', 'Tucker, O.', 'McWilliams, D.', 'Doesburg, F.', 'Cnossen, F.', 'Dieperink, W.', 'Bult, W.', 'Nijsten, M. W. N.', 'Galvez-Blanco, G. A.', 'Zepeda, E. Monares', 'Guzman, C. I. Olvera', 'Sánchez, J. S. Aguirre', 'Granillo, J. Franco', 'Stroud, J. Santos', 'Thomson, R.', 'Llaurado-Serra, M.', 'Lobo-Civico, A.', 'Pi-Guerrero, M.', 'Blanco-Sanchez, I.', 'Piñol-Tena, A.', 'Paños-Espinosa, C.', 'Alabart-Segura, Y.', 'Coloma-Gomez, B.', 'Fernandez-Blanco, A.', 'Braga-Dias, F.', 'Treso-Geira, M.', 'Valeiras-Valero, A.', 'Martinez-Reyes, L.', 'Sandiumenge, A.', 'Jimenez-Herrera, M. F.', None, 'Prada, R.', 'Juárez, P.', 'Argandoña, R.', 'Díaz, J. J.', 'Ramirez, C. Sánchez', 'Saavedra, P.', 'Santana, S. Ruiz', 'Obukhova, O.', 'Kashiya, S.', 'Kurmukov, I. A.', 'Pronina, A. M.', 'Simeone, P.', 'Puybasset, L.', 'Auzias, G.', 'Coulon, O.', 'Lesimple, B.', 'Torkomian, G.', 'Velly, L.', 'Bienert, A.', 'Bartkowska-Sniatkowska, A.', 'Wiczling, P.', 'Szerkus, O.', 'Siluk, D.', 'Bartkowiak-Wieczorek, J.', 'Rosada-Kurasinska, J.', 'Warzybok, J.', 'Borsuk, A.', 'Kaliszan, R.', 'Grzeskowiak, E.', 'Caballero, C. Hernandez', 'Roberts, S.', 'Isgro, G.', 'Hall, D.', 'Guillaume, G.', 'Passouant, O.', 'Dumas, F.', 'Bougouin, W.', 'Champigneulle, B.', 'Arnaout, M.', 'Chelly, J.', 'Chiche, J. D.', 'Varenne, O.', 'Mira, J. P.', 'Marijon, E.', 'Cariou, A.', 'Beerepoot, M.', 'Touw, H. R.', 'Parlevliet, K.', 'Boer, C.', 'Elbers, P. W.', 'Tuinman, P. R.', 'Reina, Á. J. Roldán', 'Palomo, Y. Corcia', 'Bermúdez, R. Martín', 'Villén, L. Martín', 'García, I. Palacios', 'Izurieta, J. R. Naranjo', 'Bernal, J. B. Pérez', 'Jiménez, F. J. Jiménez', None, 'Cota-Delgado, F.', 'de la Torre-Prados, M. V.', 'Fernández-Porcel, A.', 'Nuevo-Ortega, P.', 'Cámara-Sola, E.', 'Tsvetanova-Spasova, T.', 'Rueda-Molina, C.', 'Salido-Díaz, L.', 'García-Alcántara, A.', 'Kaneko, T.', 'Tanaka, H.', 'Kamikawa, M.', 'Karashima, R.', 'Iwashita, S.', 'Irie, H.', 'Kasaoka, S.', 'Arola, O.', 'Laitio, R.', 'Saraste, A.', 'Airaksinen, J.', 'Pietilä, M.', 'Hynninen, M.', 'Wennervirta, J.', 'Bäcklund, M.', 'Ylikoski, E.', 'Silvasti, P.', 'Nukarinen, E.', 'Grönlund, J.', 'Harjola, V. P.', 'Niiranen, J.', 'Korpi, K.', 'Varpula, M.', 'Roine, R. O.', 'Laitio, T.', None, 'Salah, S.', 'Hassen, B. G.', 'Fehmi, A. Mohamed', 'Kim, S.', 'Hsu, Y. C.', 'Barea-Mendoza, J.', 'García-Fuentes, C.', 'Castillo-Jaramillo, M.', 'Dominguez-Aguado, H.', 'Viejo-Moreno, R.', 'Terceros-Almanza, L.', 'Aznárez, S. Bermejo', 'Mudarra-Reche, C.', 'Xu, W.', 'Chico-Fernández, M.', 'Montejo-González, J. C.', 'Crewdson, K.', 'Thomas, M.', 'Merghani, M.', 'Fenner, L.', 'Morgan, P.', 'Lockey, D.', 'van Lieshout, E. J.', 'Oomen, B.', 'Binnekade, J. M.', 'Dongelmans, D. A.', 'de Haan, R. J.', 'Juffermans, N. P.', 'Vroom, M. B.', 'Algarte, R.', 'Martínez, L.', 'Sánchez, B.', 'Romero, I.', 'Martínez, F.', 'Quintana, S.', 'Trenado, J.', 'Sheikh, O.', 'Pogson, D.', 'Clinton, R.', 'Riccio, F.', 'Gemmell, L.', 'MacKay, A.', 'Arthur, A.', 'Young, L.', 'Sinclair, A.', 'Markopoulou, D.', 'Venetsanou, K.', 'Filippou, L.', 'Salla, E.', 'Stratouli, S.', 'Alamanos, I.', 'Guirgis, A. H.', 'Rodriguez, R. Gutiérrez', 'Lorente, M. J. Furones', 'Guarasa, I. Macias', 'Ukere, A.', 'Meisner, S.', 'Greiwe, G.', 'Opitz, B.', 'Benten, D.', 'Nashan, B.', 'Fischer, L.', 'Trepte, C. J. C.', 'Reuter, D. A.', 'Haas, S. A.', 'Behem, C. R.', 'Tavazzi, G.', 'Ana, B.', 'Vazir, A.', 'Gibson, D.', 'Price, S.', 'Masjedi, M.', 'Hadavi, M. R.', 'alam, M. Riahi', 'Sasani, M. R.', 'Parenti, N.', 'Agrusta, F.', 'Palazzi, C.', 'Pifferi, B.', 'Sganzerla, R.', 'Tagliazucchi, F.', 'Luciani, A.', 'Möller, M.', 'Müller-Engelmann, J.', 'Montag, G.', 'Adams, P.', 'Lange, C.', 'Neuzner, J.', 'Gradaus, R.', 'Wodack, K. H.', 'Thürk, F.', 'Waldmann, A. D.', 'Grässler, M. F.', 'Nishimoto, S.', 'Böhm, S. H.', 'Kaniusas, E.', 'Reuter, D. A.', 'Trepte, C. J.', 'Sigmundsson, T.', 'Öhman, T.', 'Redondo, E.', 'Hallbäck, M.', 'Wallin, M.', 'Sipman, F. Suarez', 'Oldner, A.', 'Sander, C. Hällsjö', 'Björne, H.', 'Colinas, L.', 'Hernandez, G.', 'Vicho, R.', 'Serna, M.', 'Cuena, R.', 'Canabal, A.', None, 'Chaari, A.', 'Hakim, K. Abdel', 'Etman, M.', 'El Bahr, M.', 'El Sakka, A.', 'Bousselmi, K.', 'Arali, A.', 'Kauts, V.', 'Casey, W. F.', 'Bond, O.', 'De Santis, P.', 'Iesu, E.', 'Franchi, F.', 'Vincent, J. L.', 'Creteur, J.', 'Scolletta, S.', 'Taccone, F. S.', 'Marutyan, Z.', 'Hamidova, L.', 'Shakotko, A.', 'Movsisyan, V.', 'Uysupova, I.', 'Evdokimov, A.', 'Petrikov, S.', 'Gonen, C.', 'Haftacı, E.', 'Balci, C.', 'Calvo, F. J. Redondo', 'Bejarano, N.', 'Baladron, V.', 'Villazala, R.', 'Redondo, J.', 'Padilla, D.', 'Villarejo, P.', 'Akcan-Arikan, A.', 'Kennedy, C. E.', 'Arzapalo, M. F. Aguilar', 'Gomez-Gonzalez, C.', 'Mas-Font, S.', 'Puppo-Moreno, A.', 'Herrera-Gutierrez, M.', 'Garcia-Garcia, M.', 'Aldunate-Calvo, S.', None, 'Plata-Menchaca, E. P.', 'Pérez-Fernández, X. L.', 'Estruch, M.', 'Betbese-Roig, A.', 'Campos, P. Cárdenas', 'Lora, M. Rojas', 'Gaibor, N. D. Toapanta', 'Medina, R. S. Contreras', 'Sanguino, V. D. Gumucio', 'Casanova, E. J.', 'Riera, J. Sabater', None, 'Kritmetapak, K.', 'Peerapornratana, S.', 'Kittiskulnam, P.', 'Dissayabutra, T.', 'Tiranathanagul, K.', 'Susantithapong, P.', 'Praditpornsilpa, K.', 'Tungsanga, K.', 'Eiam-Ong, S.', 'Srisawat, N.', 'Winkelmann, T.', 'Busch, T.', 'Meixensberger, J.', 'Bercker, S.', 'Cabeza, E. M. Flores', 'Sánchez, M. Sánchez', 'Giménez, N. Cáceres', 'Melón, C. Gutierrez', 'de Lucas, E. Herrero', 'Estañ, P. Millán', 'Bernal, M. Hernández', 'de Lorenzo y Mateos, A. Garcia', 'Ergin, B.', 'Guerci, P.', 'Specht, P. A. C.', 'Ince, Y.', 'Ince, C.', 'Balik, M.', 'Zakharchenko, M.', 'Los, F.', 'Brodska, H.', 'de Tymowski, C.', 'Augustin, P.', 'Desmard, M.', 'Montravers, P.', 'Stapel, S. N.', 'de Boer, R.', 'Oudemans, H. M.', 'Hollinger, A.', 'Schweingruber, T.', 'Jockers, F.', 'Dickenmann, M.', 'Siegemund, M.', None, 'Runciman, N.', 'Ralston, M.', 'Appleton, R.', 'Mauri, T.', 'Alban, L.', 'Turrini, C.', 'Sasso, T.', 'Langer, T.', 'Panigada, M.', 'Taccone, P.', 'Carlesso, E.', 'Marenghi, C.', 'Grasselli, G.', 'Pesenti, A.', 'Wibart, P.', 'Reginault, T.', 'Garcia, M.', 'Barbrel, B.', 'Benard, A.', 'Bader, C.', 'Vargas, F.', 'Bui, H. N.', 'Hilbert, G.', 'Simón, J. M. Serrano', 'Sánchez, P. Carmona', 'Ferrón, F. Ruiz', 'de Acilu, M. García', 'Marin, J.', 'Antonia, V.', 'Ruano, L.', 'Monica, M.', 'Ferrer, R.', 'Masclans, J. R.', 'Roca, O.', 'Hong, G.', 'Kim, D. H.', 'Kim, Y. S.', 'Park, J. S.', 'Jee, Y. K.', 'xiang, Z. Yu', 'Jia-xing, W.', 'dan, W. Xiao', 'long, N. Wen', 'Yu, W.', 'Yan, Z.', 'Cheng, X.', 'Kobayashi, T.', 'Onodera, Y.', 'Akimoto, R.', 'Sugiura, A.', 'Suzuki, H.', 'Iwabuchi, M.', 'Nakane, M.', 'Kawamae, K.', 'Sanchez, P. Carmona', 'Rodriguez, M. D. Bautista', 'Delgado, M. Rodriguez', 'Sánchez, V. Martínez de Pinillos', 'Gómez, A. Mula', 'Simón, J. M. Serrano', 'Beuret, P.', 'Fortes, C.', 'Lauer, M.', 'Reboul, M.', 'Chakarian, J. C.', 'Fabre, X.', 'Philippon-Jouve, B.', 'Devillez, S.', 'Clerc, M.', 'Rittayamai, N.', 'Sklar, M.', 'Dres, M.', 'Rauseo, M.', 'Campbell, C.', 'West, B.', 'Tullis, D. E.', 'Brochard, L.', 'Onodera, Y.', 'Akimoto, R.', 'Suzuki, H.', 'Okada, M.', 'Nakane, M.', 'Kawamae, K.', 'Ahmad, N.', 'Wood, M.', 'Glossop, A.', 'Lucas, J. Higuera', 'Ortiz, A. Blandino', 'Alonso, D. Cabestrero', 'De Pablo Sánchez, R.', 'González, L. Rey', 'Costa, R.', 'Spinazzola, G.', 'Pizza, A.', 'Ferrone, G.', 'Rossi, M.', 'Antonelli, M.', 'Conti, G.', 'Ribeiro, H.', 'Alves, J.', 'Sousa, M.', 'Reis, P.', 'Socolovsky, C. S.', 'Cauley, R. P.', 'Frankel, J. E.', 'Beam, A. L.', 'Olaniran, K. O.', 'Gibbons, F. K.', 'Christopher, K. B.', 'Pennington, J.', 'Zolfaghari, P.', 'King, H. S.', 'Kong, H. H. Y.', 'Shum, H. P.', 'Yan, W. W.', 'Kaymak, C.', 'Okumus, N.', 'Sari, A.', 'Erdogdu, B.', 'Aksun, S.', 'Basar, H.', 'Ozcan, A.', 'Ozcan, N.', 'Oztuna, D.', 'Malmgren, J. A.', 'Lundin, S.', 'Torén, K.', 'Eckerström, M.', 'Wallin, A.', 'Waldenström, A. C.', None, 'Riccio, F. C.', 'Pogson, D.', 'Antonio, A. C. P.', 'Leivas, A. F.', 'Kenji, F.', 'James, E.', 'Morgan, P.', 'Carroll, G.', 'Gemmell, L.', 'MacKay, A.', 'Wright, C.', 'Ballantyne, J.', 'Jonnada, S.', 'Gerrard, C. S.', 'Jones, N.', 'Salciccioli, J. D.', 'Marshall, D. C.', 'Komorowski, M.', 'Hartley, A.', 'Sykes, M. C.', 'Goodson, R.', 'Shalhoub, J.', 'Villanueva, J. R. Fernández', 'Garda, R. Fernández', 'Lago, A. M. López', 'Ruiz, E. Rodríguez', 'Vaquero, R. Hernández', 'Rodríguez, C. Galbán', 'Pérez, E. Varo', 'Hilasque, C.', 'Oliva, I.', 'Sirgo, G.', 'Martin, M. C.', 'Olona, M.', 'Gilavert, M. C.', 'Bodí, M.', 'Ebm, C.', 'Aggarwal, G.', 'Huddart, S.', 'Quiney, N.', 'Cecconi, M.', 'Fernandes, S. M.', 'Silva, J. Santos', 'Gouveia, J.', 'Silva, D.', 'Marques, R.', 'Bento, H.', 'Alvarez, A.', 'Silva, Z. Costa', 'Diaz, D. Díaz', 'Martínez, M. Villanova', 'Herrejon, E. Palencia', 'de la Gandara, A. Martinez', 'Gonzalo, G.', 'Lopez, M. A.', 'de Gopegui Miguelena, P. Ruíz', 'Matilla, C. I. Bernal', 'Chueca, P. Sánchez', 'Longares, M. D. C. Rodríguez', 'Abril, R. Ramos', 'Aguilar, A. L. Ruíz', 'de Murillas, R. Garrido López', 'Fernández, R. Fernández', 'Laborías, P. Morales', 'Castellanos, M. A. Díaz', 'Laborías, M. E. Morales', 'Cho, J.', 'Kim, J.', 'Park, J.', 'Woo, S.', 'West, T.', 'Powell, E.', 'Rimmer, A.', 'Orford, C.', 'Jones, N.', 'Williams, J.', 'Matilla, C. I. Bernal', 'de Gopegui Miguelena, P. Ruiz', 'Chueca, P. Sánchez', 'Abril, R. Ramos', 'Longares, M. D. C. Rodríguez', 'Aguilar, A. L. Ruíz', 'de Murillas, R. Garrido López', 'Bourne, R. S.', 'Shulman, R.', 'Tomlin, M.', 'Mills, G. H.', 'Borthwick, M.', 'Berry, W.', 'Huertas, D. García', 'Manzano, F.', 'Villagrán-Ramírez, F.', 'Ruiz-Perea, A.', 'Rodríguez-Mejías, C.', 'Santiago-Ruiz, F.', 'Colmenero-Ruiz, M.', 'König, C.', 'Matt, B.', 'Kortgen, A.', 'Hartog, C. S.', 'Wong, A.', 'Balan, C.', 'Barker, G.', 'Srisawat, N.', 'Peerapornratana, S.', 'Laoveeravat, P.', 'Tachaboon, S.', 'Eiam-ong, S.', 'Paratz, J.', 'Kayambu, G.', 'Boots, R.', 'Arzapalo, M. F. Aguilar', 'Vlasenko, R.', 'Gromova, E.', 'Loginov, S.', 'Kiselevskiy, M.', 'Dolgikova, Y.', 'Tang, K. B.', 'Chau, C. M.', 'Lam, K. N.', 'Gil, E.', 'Suh, G. Y.', 'Park, C. M.', 'Park, J.', 'Chung, C. R.', 'Lee, C. T.', 'Chao, A.', 'Shih, P. Y.', 'Chang, Y. F.', 'Lai, C. H.', 'Hsu, Y. C.', 'Yeh, Y. C.', 'Cheng, Y. J.', 'Colella, V.', 'Zarrillo, N.', 'D’Amico, M.', 'Forfori, F.', 'Pezza, B.', 'Laddomada, T.', 'Beltramelli, V.', 'Pizzaballa, M. L.', 'Doronzio, A.', 'Balicco, B.', 'Kiers, D.', 'van der Heijden, W.', 'Gerretsen, J.', 'de Mast, Q.', 'el Messaoudi, S.', 'Rongen, G.', 'Gomes, M.', 'Kox, M.', 'Pickkers, P.', 'Riksen, N. P.', 'Kashiwagi, Y.', 'Okada, M.', 'Hayashi, K.', 'Inagaki, Y.', 'Fujita, S.', 'Nakamae, M. N.', 'Kang, Y. R.', 'Souza, R. B.', 'Liberatore, A. M. A.', 'Koh, I. H. J.', 'Blet, A.', 'Sadoune, M.', 'Lemarié, J.', 'Bihry, N.', 'Bern, R.', 'Polidano, E.', 'Merval, R.', 'Launay, J. M.', 'Lévy, B.', 'Samuel, J. L.', 'Mebazaa, A.', 'Hartmann, J.', 'Harm, S.', 'Weber, V.']",Intensive Care Med Exp,,,True
c6b416e31cb51e4ecc6264f20bb37db28e9a4cef,PMC,Human IFIT1 Inhibits mRNA Translation of Rubulaviruses but Not Other Members of the Paramyxoviridae Family,http://dx.doi.org/10.1128/JVI.01056-16,PMC5044818,27512068,CC BY,"We have previously shown that IFIT1 is primarily responsible for the antiviral action of interferon (IFN) alpha/beta against parainfluenza virus type 5 (PIV5), selectively inhibiting the translation of PIV5 mRNAs. Here we report that while PIV2, PIV5, and mumps virus (MuV) are sensitive to IFIT1, nonrubulavirus members of the paramyxoviridae such as PIV3, Sendai virus (SeV), and canine distemper virus (CDV) are resistant. The IFIT1 sensitivity of PIV5 was not rescued by coinfection with an IFIT1-resistant virus (PIV3), demonstrating that PIV3 does not specifically inhibit the antiviral activity of IFIT1 and that the inhibition of PIV5 mRNAs is regulated by cis-acting elements. We developed an in vitro translation system using purified human IFIT1 to further investigate the mechanism of action of IFIT1. While the translations of PIV2, PIV5, and MuV mRNAs were directly inhibited by IFIT1, the translations of PIV3, SeV, and CDV mRNAs were not. Using purified human mRNA-capping enzymes, we show biochemically that efficient inhibition by IFIT1 is dependent upon a 5′ guanosine nucleoside cap (which need not be N7 methylated) and that this sensitivity is partly abrogated by 2′O methylation of the cap 1 ribose. Intriguingly, PIV5 M mRNA, in contrast to NP mRNA, remained sensitive to inhibition by IFIT1 following in vitro 2′O methylation, suggesting that other structural features of mRNAs may influence their sensitivity to IFIT1. Thus, surprisingly, the viral polymerases (which have 2′-O-methyltransferase activity) of rubulaviruses do not protect these viruses from inhibition by IFIT1. Possible biological consequences of this are discussed. IMPORTANCE Paramyxoviruses cause a wide variety of diseases, and yet most of their genes encode structural proteins and proteins involved in their replication cycle. Thus, the amount of genetic information that determines the type of disease that paramyxoviruses cause is relatively small. One factor that will influence disease outcomes is how they interact with innate host cell defenses, including the interferon (IFN) system. Here we show that different paramyxoviruses interact in distinct ways with cells in a preexisting IFN-induced antiviral state. Strikingly, all the rubulaviruses tested were sensitive to the antiviral action of ISG56/IFIT1, while all the other paramyxoviruses tested were resistant. We developed novel in vitro biochemical assays to investigate the mechanism of action of IFIT1, demonstrating that the mRNAs of rubulaviruses can be directly inhibited by IFIT1 and that this is at least partially because their mRNAs are not correctly methylated.",2016 Sep 29,"['Young, D. F.', 'Andrejeva, J.', 'Li, X.', 'Inesta-Vaquera, F.', 'Dong, C.', 'Cowling, V. H.', 'Goodbourn, S.', 'Randall, R. E.']",J Virol,,,True
a374cb0eaeb9e3cf7b9e3d4f08ff21907437c159,PMC,Characterization of Two Monoclonal Antibodies That Recognize Linker Region and Carboxyl Terminal Domain of Coronavirus Nucleocapsid Protein,http://dx.doi.org/10.1371/journal.pone.0163920,PMC5045181,27689694,CC BY,"The transmissible gastroenteritis virus (TGEV) nucleocapsid (N) protein plays important roles in the replication and translation of viral RNA. The present study provides the first description of two monoclonal antibodies (mAbs) (5E8 and 3D7) directed against the TGEV N protein linker region (LKR) and carboxyl terminal domain (CTD). The mAbs 5E8 and 3D7 reacted with native N protein in western blotting and immunofluorescence assay (IFA). Two linear epitopes, (189)SVEQAVLAALKKLG(202) and (246)VTRFYGARSSSA(257), located in the LKR and CTD of TGEV N protein, respectively, were identified after truncating the protein and applying a peptide scanning technique. Using mAb 5E8, we observed that the N protein was expressed in the cytoplasm during TGEV replication and that the protein could be immunoprecipitated from TGEV-infected PK-15 cells. The mAb 5E8 can be applied for different approaches to diagnosis of TGEV infection. In addition, the antibodies represent useful tools for investigating the antigenic properties of the N protein.",2016 Sep 30,"['Zhang, Xin', 'Zhao, Xin', 'Dong, Hui', 'Zhu, Yunnuan', 'Shi, Hongyan', 'Chen, Jianfei', 'Shi, Da', 'Feng, Li']",PLoS One,,,True
7902a01d7b2422e17f964afa1ecf05ec1e3088e7,PMC,"Awareness of droplet and airborne isolation precautions among dental health professionals during the outbreak of corona virus infection in Riyadh city, Saudi Arabia",http://dx.doi.org/10.4317/jced.52811,PMC5045684,27703605,CC BY,"BACKGROUND: This study aimed to determine knowledge, attitude and practice of airborne and droplet isolation precautions among Dental Health Professionals (DHPs) (dental students, interns, practitioners and auxiliaries) during the outbreak of MERS (Middle East Respiratory Syndrome), corona virus infection in Riyadh city, Saudi Arabia. MATERIAL AND METHODS: A cross-sectional survey was conducted among 406 dental health professionals (DHPs) working in selected dental facilities in Riyadh city, Saudi Arabia during the outbreak of MERS (April-June 2013). A structured, close-ended, self-administered questionnaire explored the knowledge, attitude, and practice towards droplet and isolation precautions. Collected data was subjected to descriptive statistics to express demographic information, mean knowledge score, mean attitude score and practice score of DHPs. Inferential statistics (Mann-Whitney U test and Kruskal Wallis tests, p < 0.05) were used to examine differences between study variables. Spearman’s rho correlation was used to identify the association between the knowledge-attitude, knowledge-practice, and attitude-practice. RESULTS: A response rate of rate of 90.22% (406 out of 452) was obtained. The mean scores of knowledge, attitude and practice were 10.61 ± 1.19, 50.54 ± 7.53 and 8.50 ± 2.14 respectively. Spearman’s correlation test revealed a significant linear positive correlation between knowledge and attitude (r-0.501, P- 0.01), knowledge and practice (r-0.185, P-0.01) and attitude and practice (r-0.351, P- 0.01) of DHPs about airborne isolation precautions. CONCLUSIONS: Dental health professionals considered in the present study showed good knowledge, positive attitude and good practice towards droplet and airborne isolation precautions during outbreak of MERS. Key words:Knowledge, attitude, practice, droplet, airborne, precaution, dental professionals.",2016 Oct 1,"['Baseer, Mohammad-Abdul', 'Ansari, Shahzeb-Hasan', 'AlShamrani, Sultan-Saleh', 'Alakras, Abdul-Rahman', 'Mahrous, Raif', 'Alenazi, Abdul-Majeed']",J Clin Exp Dent,,,True
6e6fb58bc0253b1c8326599159f321be8a37736f,PMC,Integrating one health in national health policies of developing countries: India’s lost opportunities,http://dx.doi.org/10.1186/s40249-016-0181-2,PMC5047123,27716352,CC BY,"BACKGROUND: Globally, the threat of infectious diseases, particularly emerging infectious diseases, originating at the human-animal-environment interface, has caught health systems off guard. With forecasts that future pathogen emergence will be centred in hotspots in Asia, Africa, and Latin America, the need to prepare policy frameworks that can combat this threat is urgent. DISCUSSION: Emergence of diseases such as avian influenza and Ebola virus disease, which threatened social disruption, have established the need for intersectoral coordination/collaboration. These events led to the initiation of establishing institutionalised collaborative frameworks in India to adopt a One Health approach to disease prevention and control. However, the gains made in influenza control could not be adapted to other infectious diseases. Intersectoral coordination was briefly carried out, more as a reactive response to threats. The systemic failure to sustain such efforts have therefore, only undermined a coordinated response. The recent draft National Health Policy, 2015, has also failed to establish the need for intersectoral coordination in disease control approaches. Neglecting the need to endorse linkages between human health, animal health and husbandry, agriculture, and environmental sectors, has led to duplicative and weak response systems. The absence of health impact assessment with respect to the development agenda in policies, has cast negative effects on the health and wellbeing of man, animal, and the environment. Lack of attention to building core capacity in these critical sectors has further raised challenges in designing and deploying mitigation strategies. With developing countries like India being home to a major portion of the world’s poorest livestock farmers, the absence of a policy discourse that endorses the One Health approach in development and health policies is a major hurdle in eliminating poverty and poverty-related diseases. CONCLUSIONS: The adoption of One Health approaches in health and related sectoral policies is a critical policy requirement for India and other developing countries. The goal should be to not just establish preparedness plans, but also to encourage a policy environment where assessment and mitigation of downstream impacts of different agenda are incorporated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0181-2) contains supplementary material, which is available to authorized users.",2016 Oct 3,"['Chatterjee, Pranab', 'Kakkar, Manish', 'Chaturvedi, Sanjay']",Infect Dis Poverty,,,True
f6e7d1aaef6479469705a2ae0ea9a5e5a5e18abf,PMC,Immunoregulatory functions of immune complexes in vaccine and therapy,http://dx.doi.org/10.15252/emmm.201606593,PMC5048363,27572622,CC BY,"Clinical and experimental preparations of IgG/soluble antigen complexes, as well as those formed following antibody therapy in vivo, are multifaceted immune regulators. These immune complexes (ICs) have been tested in humans and animal models, mostly in forms of experimental or clinical vaccination, for at least a century. With intensified research on Fcγ receptor‐mediated immune modulation, as well as with immune complex‐directed antigen processing, presentation, and inflammatory responses, there are renewed interests of using ICs in vaccines and immunotherapies. Currently, IC‐based immune therapy has been broadly experimented in HBV and HIV viral infection control and antitumor treatments. However, mechanistic insights of IC‐based treatments are relatively recent subjects of study; strong efforts are needed to establish links to connect laboratory findings with clinical practices. This review covers the history, mechanisms, and in vivo outcomes of this safe and effective therapeutic tool, with a clear aim to bridge laboratory findings with evolving clinical applications.",2016 Oct 29,"['Wen, Yu‐mei', 'Mu, Libing', 'Shi, Yan']",EMBO Mol Med,,,True
de8f4493515bdf7ed934509024d19a66dc57016f,PMC,"Factors associated with clinical outcome in 25 patients with avian influenza A (H7N9) infection in Guangzhou, China",http://dx.doi.org/10.1186/s12879-016-1840-4,PMC5048464,27716101,CC BY,"BACKGROUND: Guangzhou reported its first laboratory-confirmed case of influenza A (H7N9) on January 10, 2014. A total of 25 cases were reported from the first wave of the epidemic until April 8, 2014. The fatality rate was much higher than in previous reports. The objective of the current work was to describe the clinical and epidemiological characteristics of A (H7N9) patients in Guangzhou and explore possible reasons for the high fatality rate. METHODS: Clinical and epidemiological information regarding A (H7N9) cases in Guangzhou was collected through review of medical records and field research. Data regarding clinical and laboratory features, treatment, and outcomes were extracted. RESULTS: Of the 25 patients, 84 % (21/25) had one or more underlying diseases. Fifteen patients (60.0 %) developed moderate to severe acute respiratory distress syndrome (ARDS), and 14 (56 %) died of the ARDS or multiorgan failure. Patients with longer delay between onset of illness and initiation of oseltamivir treatment were more likely to develop ARDS. Elevated C-creative protein, aspartate aminotransferase, creatine kinase, and lymphocytopenia predicted a higher risk of developing ARDS. CONCLUSIONS: The presence of underlying diseases and clinical complications predicted poor clinical outcome. Early oseltamivir treatment was associated with a reduced risk of developing ARDS.",2016 Oct 3,"['Wang, Hui', 'Xiao, XinCai', 'Lu, Jianyun', 'Chen, Zongqiu', 'Li, Kuibiao', 'Liu, Hui', 'Luo, Lei', 'Wang, Ming', 'Yang, ZhiCong']",BMC Infect Dis,,,True
18421f153f74c6b0f8f9efe88c2aad6b70547b99,PMC,Dissecting the Effect of Genetic Variation on the Hepatic Expression of Drug Disposition Genes across the Collaborative Cross Mouse Strains,http://dx.doi.org/10.3389/fgene.2016.00172,PMC5050206,27761138,CC BY,"A central challenge in pharmaceutical research is to investigate genetic variation in response to drugs. The Collaborative Cross (CC) mouse reference population is a promising model for pharmacogenomic studies because of its large amount of genetic variation, genetic reproducibility, and dense recombination sites. While the CC lines are phenotypically diverse, their genetic diversity in drug disposition processes, such as detoxification reactions, is still largely uncharacterized. Here we systematically measured RNA-sequencing expression profiles from livers of 29 CC lines under baseline conditions. We then leveraged a reference collection of metabolic biotransformation pathways to map potential relations between drugs and their underlying expression quantitative trait loci (eQTLs). By applying this approach on proximal eQTLs, including eQTLs acting on the overall expression of genes and on the expression of particular transcript isoforms, we were able to construct the organization of hepatic eQTL-drug connectivity across the CC population. The analysis revealed a substantial impact of genetic variation acting on drug biotransformation, allowed mapping of potential joint genetic effects in the context of individual drugs, and demonstrated crosstalk between drug metabolism and lipid metabolism. Our findings provide a resource for investigating drug disposition in the CC strains, and offer a new paradigm for integrating biotransformation reactions to corresponding variations in DNA sequences.",2016 Oct 5,"['Nachshon, Aharon', 'Abu-Toamih Atamni, Hanifa J.', 'Steuerman, Yael', ""Sheikh-Hamed, Roa'a"", 'Dorman, Alexandra', 'Mott, Richard', 'Dohm, Juliane C.', 'Lehrach, Hans', 'Sultan, Marc', 'Shamir, Ron', 'Sauer, Sascha', 'Himmelbauer, Heinz', 'Iraqi, Fuad A.', 'Gat-Viks, Irit']",Front Genet,,,True
7072f43043b3cbcaffc357902409ece63bc6f828,PMC,Next-Generation High-Throughput Functional Annotation of Microbial Genomes,http://dx.doi.org/10.1128/mBio.01245-16,PMC5050336,27703071,CC BY,"Host infection by microbial pathogens cues global changes in microbial and host cell biology that facilitate microbial replication and disease. The complete maps of thousands of bacterial and viral genomes have recently been defined; however, the rate at which physiological or biochemical functions have been assigned to genes has greatly lagged. The National Institute of Allergy and Infectious Diseases (NIAID) addressed this gap by creating functional genomics centers dedicated to developing high-throughput approaches to assign gene function. These centers require broad-based and collaborative research programs to generate and integrate diverse data to achieve a comprehensive understanding of microbial pathogenesis. High-throughput functional genomics can lead to new therapeutics and better understanding of the next generation of emerging pathogens by rapidly defining new general mechanisms by which organisms cause disease and replicate in host tissues and by facilitating the rate at which functional data reach the scientific community.",2016 Oct 4,"['Baric, Ralph S.', 'Crosson, Sean', 'Damania, Blossom', 'Miller, Samuel I.', 'Rubin, Eric J.']",mBio,,,True
04a0ec4b6cb5eeb0d2cbf2c8ea8829b5c476b1b9,PMC,"Serological patterns of Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae, Pasteurella multocida and Streptococcus suis in pig herds affected by pleuritis",http://dx.doi.org/10.1186/s13028-016-0252-1,PMC5050615,27716292,CC BY,"BACKGROUND: Respiratory illness is traditionally regarded as the disease of the growing pig, and has historically mainly been associated to bacterial infections with focus on Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. These bacteria still are of great importance, but continuously increasing herd sizes have complicated the scenario and the influence of secondary invaders may have been increased. The aim of this study was to evaluate the presence of A. pleuropneumoniae and M. hyopneumoniae, as well as that of the secondary invaders Pasteurella multocida and Streptococcus suis by serology in four pig herds (A–D) using age segregated rearing systems with high incidences of pleuritic lesions at slaughter. RESULTS: Pleuritic lesions registered at slaughter ranged from 20.5 to 33.1 % in the four herds. In herd A, the levels of serum antibodies to A. pleuropneumoniae exceeded A(450) > 1.5, but not to any other microbe searched for. The seroconversion took place early during the fattening period. Similar levels of serum antibodies to A. pleuropneumoniae were also recorded in herd B, with a subsequent increase in levels of antibodies to P. multocida. Pigs seroconverted to both agents during the early phase of the fattening period. In herd C, pigs seroconverted to P. multocida during the early phase of the fattening period and thereafter to A. pleuropneumoniae. In herd D, the levels of antibodies to P. multocida exceeded A(450) > 1.0 in absence (A(450) < 0.5) of antibodies to A. pleuropneumoniae. The levels of serum antibodies to M. hyopneumoniae and to S. suis remained below A(450) < 1.0 in all four herds. Pigs seroconverted to M. hyopneumoniae late during the rearing period (herd B–D), or not at all (herd A). CONCLUSION: Different serological patterns were found in the four herds with high levels of serum antibodies to A. pleuropneumoniae and P. multocida, either alone or in combination with each other. Seroconversion to M. hyopneumoniae late during the rearing period or not at all, confirmed the positive effect of age segregated rearing in preventing or delaying infections with M. hyopneumoniae. The results obtained highlight the necessity of diagnostic investigations to define the true disease pattern in herds with a high incidence of pleuritic lesions.",2016 Oct 4,"['Wallgren, Per', 'Nörregård, Erik', 'Molander, Benedicta', 'Persson, Maria', 'Ehlorsson, Carl-Johan']",Acta Vet Scand,,,True
953d78fb78ffe2bd8db79fac2390d45bd28a4952,PMC,CCR5 ameliorates Japanese encephalitis via dictating the equilibrium of regulatory CD4(+)Foxp3(+) T and IL-17(+)CD4(+) Th17 cells,http://dx.doi.org/10.1186/s12974-016-0656-x,PMC5050958,27439902,CC BY,"BACKGROUND: CCR5 is a CC chemokine receptor involved in the migration of effector leukocytes including macrophages, NK, and T cells into inflamed tissues. Also, the role of CCR5 in CD4(+)Foxp3(+) regulatory T cell (Treg) homing has recently begun to grab attention. Japanese encephalitis (JE) is defined as severe neuroinflammation of the central nervous system (CNS) following infection with mosquito-borne flavivirus JE virus. However, the potential contribution of CCR5 to JE progression via mediating CD4(+)Foxp3(+) Treg homing has not been investigated. METHODS: Infected wild-type (Ccr5(+/+)) and CCR5-deficient (Ccr5(−/−)) mice were examined daily for mortality and clinical signs, and neuroinflammation in the CNS was evaluated by infiltration of inflammatory leukocytes and cytokine expression. In addition, viral burden, NK- and JEV-specific T cell responses were analyzed. Adoptive transfer of CCR5(+)CD4(+)Foxp3(+) Tregs was used to evaluate the role of Tregs in JE progression. RESULTS: CCR5 ablation exacerbated JE without altering viral burden in the extraneural and CNS tissues, as manifested by increased CNS infiltration of Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. Compared to Ccr5(+/+) mice, Ccr5(−/−) mice unexpectedly showed increased responses of IFN-γ(+)NK and CD8(+) T cells in the spleen, but not CD4(+) T cells. More interestingly, CCR5-ablation resulted in a skewed response to IL-17(+)CD4(+) Th17 cells and correspondingly reduced CD4(+)Foxp3(+) Tregs in the spleen and brain, which was closely associated with exacerbated JE. Our results also revealed that adoptive transfer of sorted CCR5(+)CD4(+)Foxp3(+) Tregs into Ccr5(−/−) mice could ameliorate JE progression without apparently altering the viral burden and CNS infiltration of IL-17(+)CD4(+) Th17 cells, myeloid-derived Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. Instead, adoptive transfer of CCR5(+)CD4(+)Foxp3(+) Tregs into Ccr5(−/−) mice resulted in increased expression of anti-inflammatory cytokines (IL-10 and TGF-β) in the spleen and brain, and transferred CCR5(+) Tregs were found to produce IL-10. CONCLUSIONS: CCR5 regulates JE progression via governing timely and appropriate CNS infiltration of CD4(+)Foxp3(+) Tregs, thereby facilitating host survival. Therefore, this critical and extended role of CCR5 in JE raises possible safety concerns regarding the use of CCR5 antagonists in human immunodeficiency virus (HIV)-infected individuals who inhabit regions in which both HIV and flaviviruses, such as JEV and West Nile virus, are endemic.",2016 Jul 20,"['Kim, Jin Hyoung', 'Patil, Ajit Mahadev', 'Choi, Jin Young', 'Kim, Seong Bum', 'Uyangaa, Erdenebelig', 'Hossain, Ferdaus Mohd Altaf', 'Park, Sang-Youel', 'Lee, John Hwa', 'Eo, Seong Kug']",J Neuroinflammation,,,True
691856452de91727b7b9b7644f82b4bc5876f32f,PMC,MERS-CoV at the Animal–Human Interface: Inputs on Exposure Pathways from an Expert-Opinion Elicitation,http://dx.doi.org/10.3389/fvets.2016.00088,PMC5051548,27761437,CC BY,"Nearly 4 years after the first report of the emergence of Middle-East respiratory syndrome Coronavirus (MERS-CoV) and nearly 1800 human cases later, the ecology of MERS-CoV, its epidemiology, and more than risk factors of MERS-CoV transmission between camels are poorly understood. Knowledge about the pathways and mechanisms of transmission from animals to humans is limited; as of yet, transmission risks have not been quantified. Moreover the divergent sanitary situations and exposures to animals among populations in the Arabian Peninsula, where human primary cases appear to dominate, vs. other regions in the Middle East and Africa, with no reported human clinical cases and where the virus has been detected only in dromedaries, represents huge scientific and health challenges. Here, we have used expert-opinion elicitation in order to obtain ideas on relative importance of MERS-CoV risk factors and estimates of transmission risks from various types of contact between humans and dromedaries. Fourteen experts with diverse and extensive experience in MERS-CoV relevant fields were enrolled and completed an online questionnaire that examined pathways based on several scenarios, e.g., camels–camels, camels–human, bats/other species to camels/humans, and the role of diverse biological substances (milk, urine, etc.) and potential fomites. Experts believed that dromedary camels play the largest role in MERS-CoV infection of other dromedaries; however, they also indicated a significant influence of the season (i.e. calving or weaning periods) on transmission risk. All experts thought that MERS-CoV-infected dromedaries and asymptomatic humans play the most important role in infection of humans, with bats and other species presenting a possible, but yet undefined, risk. Direct and indirect contact of humans with dromedary camels were identified as the most risky types of contact, when compared to consumption of various camel products, with estimated “most likely” incidence risks of at least 22 and 13% for direct and indirect contact, respectively. The results of our study are consistent with available, yet very limited, published data regarding the potential pathways of transmission of MERS-CoV at the animal–human interface. These results identify key knowledge gaps and highlight the need for more comprehensive, yet focused research to be conducted to better understand transmission between dromedaries and humans.",2016 Oct 5,"['Funk, Anna L.', 'Goutard, Flavie Luce', 'Miguel, Eve', 'Bourgarel, Mathieu', 'Chevalier, Veronique', 'Faye, Bernard', 'Peiris, J. S. Malik', 'Van Kerkhove, Maria D.', 'Roger, Francois Louis']",Front Vet Sci,,,True
6318351120824de3f612d0dbdd9611f4c94bf071,PMC,Saliva between normal and pathological. Important factors in determining systemic and oral health,,PMC5052503,20112475,CC BY,"There is a tendency in current medical research to explore the importance and symptomatology of saliva. The question to which increasingly more researchers from the medico-legal, systemic and dental fields tried to answer and bring together arguments for a greater emphasis is referring to the role of saliva in the health of the patient. Up until our time, people have looked at the importance of saliva from another perspective: saliva helped in pasting envelopes or stamps, or mostly in reported cases of public speakers faced with the impossibility of having a coherent speech due to sensations of dry mouth. This ‘dry mouth’ condition, named xerostomia in medical terms, has been used since antiquity as a test in detecting lies, knowing since then that the inhibition of emotional salivary glands, the feeling of ‘dry mouth’ is caused by anxiety, thus being a potential incrimination. Although hundreds of publications have insisted on the etiology and complications of the salivary gland hypofunction, only a few health professionals used to harvest saliva tests. As in the case of urine and blood, saliva quality and quantity are affected by a multitude of medical conditions and treatments, as well as the patient's psychological state. A review of the formation, function and dysfunction of salivary glands may convey the significant role played by saliva in health and disease, especially in detection and recognition of salivary gland hypofunction, systemic disease, and the psychological states, and thus prevent complications caused by these conditions.",2009 Jul-Sep,"Iorgulescu, Gabriela",J Med Life,,,False
131e6a035170ed5bd2dba6bec02649e9508a0c55,PMC,PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with reciprocal balance of Th17 and Tregs,http://dx.doi.org/10.1038/srep34617,PMC5052580,27708408,CC BY,"PTEN is a tyrosine phosphatase with significant function in inhibiting STAT3 activation. Recently, inactivation of STAT3 has been demonstrated as a therapeutic candidate for autoimmune arthritis. The expression of PTEN controlled by p53 regulates autoimmune arthritis through modulating the balance between Th17 and Treg. We hypothesized that PTEN regulated by p53 might reduce CIA severity and inflammatory response via inhibiting STAT3 activation. Our results revealed that PTEN could ameliorate experimental autoimmune arthritis by reducing STAT3 activity and Th17 differentiation. Systemic infusion of PTEN overexpression downregulated CIA severity. In addition, PTEN overexpression decreased the activation of T cells and modulated reciprocal differentiation of Th17 and Treg cells. We observed that PTEN expression downregulated by p53 deficiency induced the activation of STAT3. Loss of p53 exacerbated autoimmune arthritis and dysregulated the population of Th17 and Treg. These data suggest that induction of STAT3-modulatory activity of PTEN may be a therapeutic target for rheumatoid arthritis therapy.",2016 Oct 6,"['Lee, Seung Hoon', 'Park, Jin-Sil', 'Byun, Jae-Kyung', 'Jhun, JooYeon', 'Jung, KyungAh', 'Seo, Hyeon-Beom', 'Moon, Young-Mee', 'Kim, Ho-Youn', 'Park, Sung-Hwan', 'Cho, Mi-La']",Sci Rep,,,True
682ccd02287c5c36f05186e68f2cd195fcc20641,PMC,PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with reciprocal balance of Th17 and Tregs,http://dx.doi.org/10.1038/srep34617,PMC5052580,27708408,CC BY,"PTEN is a tyrosine phosphatase with significant function in inhibiting STAT3 activation. Recently, inactivation of STAT3 has been demonstrated as a therapeutic candidate for autoimmune arthritis. The expression of PTEN controlled by p53 regulates autoimmune arthritis through modulating the balance between Th17 and Treg. We hypothesized that PTEN regulated by p53 might reduce CIA severity and inflammatory response via inhibiting STAT3 activation. Our results revealed that PTEN could ameliorate experimental autoimmune arthritis by reducing STAT3 activity and Th17 differentiation. Systemic infusion of PTEN overexpression downregulated CIA severity. In addition, PTEN overexpression decreased the activation of T cells and modulated reciprocal differentiation of Th17 and Treg cells. We observed that PTEN expression downregulated by p53 deficiency induced the activation of STAT3. Loss of p53 exacerbated autoimmune arthritis and dysregulated the population of Th17 and Treg. These data suggest that induction of STAT3-modulatory activity of PTEN may be a therapeutic target for rheumatoid arthritis therapy.",2016 Oct 6,"['Lee, Seung Hoon', 'Park, Jin-Sil', 'Byun, Jae-Kyung', 'Jhun, JooYeon', 'Jung, KyungAh', 'Seo, Hyeon-Beom', 'Moon, Young-Mee', 'Kim, Ho-Youn', 'Park, Sung-Hwan', 'Cho, Mi-La']",Sci Rep,,,False
9c1c6037784f97a987e79a92077dad0d252b7236,PMC,Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments,http://dx.doi.org/10.1038/ncomms12761,PMC5052702,27677239,CC BY,"Small-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities. Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors. A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme. The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections. Using an aldehyde-epoxide as bis-electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry. The structure of one enzyme–inhibitor complex is determined by X-ray crystallography. The presented warhead activation assay provides potent non-peptidic, broad-spectrum inhibitors of enteroviral proteases.",2016 Sep 28,"['Becker, Daniel', 'Kaczmarska, Zuzanna', 'Arkona, Christoph', 'Schulz, Robert', 'Tauber, Carolin', 'Wolber, Gerhard', 'Hilgenfeld, Rolf', 'Coll, Miquel', 'Rademann, Jörg']",Nat Commun,,,True
4146f749b0883891603380e62be449df9a94a1a3,PMC,Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments,http://dx.doi.org/10.1038/ncomms12761,PMC5052702,27677239,CC BY,"Small-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities. Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors. A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme. The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections. Using an aldehyde-epoxide as bis-electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry. The structure of one enzyme–inhibitor complex is determined by X-ray crystallography. The presented warhead activation assay provides potent non-peptidic, broad-spectrum inhibitors of enteroviral proteases.",2016 Sep 28,"['Becker, Daniel', 'Kaczmarska, Zuzanna', 'Arkona, Christoph', 'Schulz, Robert', 'Tauber, Carolin', 'Wolber, Gerhard', 'Hilgenfeld, Rolf', 'Coll, Miquel', 'Rademann, Jörg']",Nat Commun,,,True
5c56a1f3c469648d2e726e5c0d7bca623749a10b,PMC,Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments,http://dx.doi.org/10.1038/ncomms12761,PMC5052702,27677239,CC BY,"Small-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities. Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors. A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme. The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections. Using an aldehyde-epoxide as bis-electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry. The structure of one enzyme–inhibitor complex is determined by X-ray crystallography. The presented warhead activation assay provides potent non-peptidic, broad-spectrum inhibitors of enteroviral proteases.",2016 Sep 28,"['Becker, Daniel', 'Kaczmarska, Zuzanna', 'Arkona, Christoph', 'Schulz, Robert', 'Tauber, Carolin', 'Wolber, Gerhard', 'Hilgenfeld, Rolf', 'Coll, Miquel', 'Rademann, Jörg']",Nat Commun,,,False
d09b4a75ec07b2369281492d99c716bc3e0eba5e,PMC,Preparedness for Zika virus testing in the World Health Organization Western Pacific Region,http://dx.doi.org/10.5365/WPSAR.2016.7.1.007,PMC5052899,27757256,CC BY,"On 1 February 2016, the World Health Organization (WHO) declared that clusters of microcephaly cases and other neurological disorders occurring in Zika virus (ZIKV)-affected areas constituted a public health emergency of international concern. Increased surveillance of the virus, including the requirement for laboratory confirmation of infection, was recommended. The WHO Regional Office for the Western Pacific therefore initiated a rapid survey among national-level public health laboratories in 19 countries and areas to determine regional capacity for ZIKV detection. The survey indicated that 16/19 (84%) countries had capacity for molecular detection of ZIKV while others facilitated testing through referral. These results suggest that robust laboratory capacity is in place to support ZIKV surveillance in the Western Pacific Region.",2016 Mar 31,"['Squires, Raynal C', 'Konings, Frank', None]",Western Pac Surveill Response J,,,True
bedec26c3620f77256b9abfba6f57bc7570297b5,PMC,Perceptions on the risk communication strategy during the 2013 avian influenza A/H7N9 outbreak in humans in China: a focus group study,http://dx.doi.org/10.5365/WPSAR.2016.7.1.005,PMC5053133,27757257,CC BY,"OBJECTIVE: To identify the general public’s perceptions of the overall risk communication strategy carried out by Chinese public health agencies during the first wave of avian influenza A(H7N9) outbreak in humans in 2013. METHODS: Participants were recruited from communities in Beijing, Lanzhou and Hangzhou, China in May and June 2013 by convenience sampling. Demographics and other relevant information were collected using a self-administered questionnaire. Focus group interviews were conducted using a set of nine pre-developed questions and a tested moderator guide. The interviews were audio recorded and were transcribed verbatim. The constant comparative method was used to identify trends and themes. RESULTS: A total of nine focus group interviews, with 94 participants recruited from nine communities, were conducted. Most participants received H7N9 information via television and the Internet. Most the participants appreciated the transparency and timeliness of the information released by the government. They expressed a sense of trust in the recommended public health advice and followed most of them. The participants suggested that the government release more information about clinical treatment outcomes, have more specific health recommendations that are practical to their settings and expand the use of new media channels for risk communication. CONCLUSION: The public perceived the overall risk communication strategy by the Chinese public health agencies as effective, though the moderator had a governmental agency title that might have biased the results. There is a need to expand the use of social media for risk communication in the future.",2016 Jul 11,"['Li, Richun', 'Xie, Ruiqian', 'Yang, Chong', 'Frost, Melinda']",Western Pac Surveill Response J,,,True
acf54b736dacc46a77d7f071f9c0cb9c14b2fc19,PMC,Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence,http://dx.doi.org/10.1371/journal.pntd.0005047,PMC5053439,27711108,CC BY,"Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice, compared with its parental virus MP-12, highlighting the contribution of NSs-mediated general transcription inhibition towards RVFV virulence.",2016 Oct 6,"['Terasaki, Kaori', 'Ramirez, Sydney I.', 'Makino, Shinji']",PLoS Negl Trop Dis,,,True
0ee1c7181e45a196ce3e91a128cc64426fa6de5e,PMC,XRN1 Is a Species-Specific Virus Restriction Factor in Yeasts,http://dx.doi.org/10.1371/journal.ppat.1005890,PMC5053509,27711183,CC BY,"In eukaryotes, the degradation of cellular mRNAs is accomplished by Xrn1 and the cytoplasmic exosome. Because viral RNAs often lack canonical caps or poly-A tails, they can also be vulnerable to degradation by these host exonucleases. Yeast lack sophisticated mechanisms of innate and adaptive immunity, but do use RNA degradation as an antiviral defense mechanism. We find a highly refined, species-specific relationship between Xrn1p and the “L-A” totiviruses of different Saccharomyces yeast species. We show that the gene XRN1 has evolved rapidly under positive natural selection in Saccharomyces yeast, resulting in high levels of Xrn1p protein sequence divergence from one yeast species to the next. We also show that these sequence differences translate to differential interactions with the L-A virus, where Xrn1p from S. cerevisiae is most efficient at controlling the L-A virus that chronically infects S. cerevisiae, and Xrn1p from S. kudriavzevii is most efficient at controlling the L-A-like virus that we have discovered within S. kudriavzevii. All Xrn1p orthologs are equivalent in their interaction with another virus-like parasite, the Ty1 retrotransposon. Thus, Xrn1p appears to co-evolve with totiviruses to maintain its potent antiviral activity and limit viral propagation in Saccharomyces yeasts. We demonstrate that Xrn1p physically interacts with the Gag protein encoded by the L-A virus, suggesting a host-virus interaction that is more complicated than just Xrn1p-mediated nucleolytic digestion of viral RNAs.",2016 Oct 6,"['Rowley, Paul A.', 'Ho, Brandon', 'Bushong, Sarah', 'Johnson, Arlen', 'Sawyer, Sara L.']",PLoS Pathog,,,True
4562513d3f2f9c259d9ce5a0eae9233dbf8b8f87,PMC,Mitophagy in TGEV infection counteracts oxidative stress and apoptosis,http://dx.doi.org/10.18632/oncotarget.8345,PMC5053637,27027356,CC BY,"The intestinal epithelial cells contain a large number of mitochondria for persisting absorption and barrier function. Selective autophagy of mitochondria (mitophagy) plays an important role in the quality control of mitochondria and maintenance of cell homeostasis. Transmissible gastroenteritis virus (TGEV) is a porcine enteropathogenic coronavirus which induces malabsorption and lethal watery diarrhea in suckling piglets. The role of mitophagy in the pathological changes caused by TGEV infection is unclear. Here, we report that TGEV induces mitophagy to suppress oxidative stress and apoptosis induced by viral infection in porcine epithelial cells (IPEC-J2). We observe that TGEV infection induce mitochondrial injury, abnormal morphology, complete mitophagy, and without obvious apoptosis after TGEV infection. Meanwhile, TGEV also induces DJ-1 and some antioxidant genes upregulation to suppress oxidative stress induced by viral infection. Furthermore, silencing DJ-1 inhibit mitophagy and increase apoptosis after TGEV infection. In addition, we demonstrate for the first time that viral nucleocapsid protein (N) is located in mitochondria and mitophagosome during virus infection or be expressed alone. Those results provide a novel perspective for further improvement of prevention and treatment in TGEV infection. These results suggest that TGEV infection induce mitophagy to promote cell survival and possibly viral infection.",2016 Mar 24,"['Zhu, Liqi', 'Mou, Chunxiao', 'Yang, Xing', 'Lin, Jian', 'Yang, Qian']",Oncotarget,,,True
bd81a285e936f3dd23d16b859c50e05716066c66,PMC,Mitophagy in TGEV infection counteracts oxidative stress and apoptosis,http://dx.doi.org/10.18632/oncotarget.8345,PMC5053637,27027356,CC BY,"The intestinal epithelial cells contain a large number of mitochondria for persisting absorption and barrier function. Selective autophagy of mitochondria (mitophagy) plays an important role in the quality control of mitochondria and maintenance of cell homeostasis. Transmissible gastroenteritis virus (TGEV) is a porcine enteropathogenic coronavirus which induces malabsorption and lethal watery diarrhea in suckling piglets. The role of mitophagy in the pathological changes caused by TGEV infection is unclear. Here, we report that TGEV induces mitophagy to suppress oxidative stress and apoptosis induced by viral infection in porcine epithelial cells (IPEC-J2). We observe that TGEV infection induce mitochondrial injury, abnormal morphology, complete mitophagy, and without obvious apoptosis after TGEV infection. Meanwhile, TGEV also induces DJ-1 and some antioxidant genes upregulation to suppress oxidative stress induced by viral infection. Furthermore, silencing DJ-1 inhibit mitophagy and increase apoptosis after TGEV infection. In addition, we demonstrate for the first time that viral nucleocapsid protein (N) is located in mitochondria and mitophagosome during virus infection or be expressed alone. Those results provide a novel perspective for further improvement of prevention and treatment in TGEV infection. These results suggest that TGEV infection induce mitophagy to promote cell survival and possibly viral infection.",2016 Mar 24,"['Zhu, Liqi', 'Mou, Chunxiao', 'Yang, Xing', 'Lin, Jian', 'Yang, Qian']",Oncotarget,,,False
206121388211d800150c316cd04daeaec547032b,PMC,Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells,http://dx.doi.org/10.1038/srep34589,PMC5054393,27713552,CC BY,"The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.",2016 Oct 7,"['Hölzer, Martin', 'Krähling, Verena', 'Amman, Fabian', 'Barth, Emanuel', 'Bernhart, Stephan H.', 'Carmelo, Victor A. O.', 'Collatz, Maximilian', 'Doose, Gero', 'Eggenhofer, Florian', 'Ewald, Jan', 'Fallmann, Jörg', 'Feldhahn, Lasse M.', 'Fricke, Markus', 'Gebauer, Juliane', 'Gruber, Andreas J.', 'Hufsky, Franziska', 'Indrischek, Henrike', 'Kanton, Sabina', 'Linde, Jörg', 'Mostajo, Nelly', 'Ochsenreiter, Roman', 'Riege, Konstantin', 'Rivarola-Duarte, Lorena', 'Sahyoun, Abdullah H.', 'Saunders, Sita J.', 'Seemann, Stefan E.', 'Tanzer, Andrea', 'Vogel, Bertram', 'Wehner, Stefanie', 'Wolfinger, Michael T.', 'Backofen, Rolf', 'Gorodkin, Jan', 'Grosse, Ivo', 'Hofacker, Ivo', 'Hoffmann, Steve', 'Kaleta, Christoph', 'Stadler, Peter F.', 'Becker, Stephan', 'Marz, Manja']",Sci Rep,,,True
d64f2458851579ca8041d557f759eb0f8d515d6c,PMC,Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells,http://dx.doi.org/10.1038/srep34589,PMC5054393,27713552,CC BY,"The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.",2016 Oct 7,"['Hölzer, Martin', 'Krähling, Verena', 'Amman, Fabian', 'Barth, Emanuel', 'Bernhart, Stephan H.', 'Carmelo, Victor A. O.', 'Collatz, Maximilian', 'Doose, Gero', 'Eggenhofer, Florian', 'Ewald, Jan', 'Fallmann, Jörg', 'Feldhahn, Lasse M.', 'Fricke, Markus', 'Gebauer, Juliane', 'Gruber, Andreas J.', 'Hufsky, Franziska', 'Indrischek, Henrike', 'Kanton, Sabina', 'Linde, Jörg', 'Mostajo, Nelly', 'Ochsenreiter, Roman', 'Riege, Konstantin', 'Rivarola-Duarte, Lorena', 'Sahyoun, Abdullah H.', 'Saunders, Sita J.', 'Seemann, Stefan E.', 'Tanzer, Andrea', 'Vogel, Bertram', 'Wehner, Stefanie', 'Wolfinger, Michael T.', 'Backofen, Rolf', 'Gorodkin, Jan', 'Grosse, Ivo', 'Hofacker, Ivo', 'Hoffmann, Steve', 'Kaleta, Christoph', 'Stadler, Peter F.', 'Becker, Stephan', 'Marz, Manja']",Sci Rep,,,True
6ad4ebbfb6b68ed621ad2d67db85fac7ab6dc3cc,PMC,Fundamentals of aerosol therapy in critical care,http://dx.doi.org/10.1186/s13054-016-1448-5,PMC5054555,27716346,CC BY,"Drug dosing in critically ill patients is challenging due to the altered drug pharmacokinetics–pharmacodynamics associated with systemic therapies. For many drug therapies, there is potential to use the respiratory system as an alternative route for drug delivery. Aerosol drug delivery can provide many advantages over conventional therapy. Given that respiratory diseases are the commonest causes of critical illness, use of aerosol therapy to provide high local drug concentrations with minimal systemic side effects makes this route an attractive option. To date, limited evidence has restricted its wider application. The efficacy of aerosol drug therapy depends on drug-related factors (particle size, molecular weight), device factors, patient-related factors (airway anatomy, inhalation patterns) and mechanical ventilation-related factors (humidification, airway). This review identifies the relevant factors which require attention for optimization of aerosol drug delivery that can achieve better drug concentrations at the target sites and potentially improve clinical outcomes.",2016 Oct 7,"['Dhanani, Jayesh', 'Fraser, John F.', 'Chan, Hak-Kim', 'Rello, Jordi', 'Cohen, Jeremy', 'Roberts, Jason A.']",Crit Care,,,True
adbfd5297c83ec9c3bec89f2cf68b2715034c4d4,PMC,Therapeutic potential of the renin angiotensin system in ischaemic stroke,http://dx.doi.org/10.1186/s13231-016-0022-1,PMC5054604,27761230,CC BY,"The renin angiotensin system (RAS) consists of the systemic hormone system, critically involved in regulation and homeostasis of normal physiological functions [i.e. blood pressure (BP), blood volume regulation], and an independent brain RAS, which is involved in the regulation of many functions such as memory, central control of BP and metabolic functions. In general terms, the RAS consists of two opposing axes; the ‘classical axis’ mediated primarily by Angiotensin II (Ang II), and the ‘alternative axis’ mediated mainly by Angiotensin-(1–7) (Ang-(1–7)). An imbalance of these two opposing axes is thought to exist between genders and is thought to contribute to the pathology of cardiovascular conditions such as hypertension, a stroke co-morbidity. Ischaemic stroke pathophysiology has been shown to be influenced by components of the RAS with specific RAS receptor antagonists and agonists improving outcome in experimental models of stroke. Manipulation of the two opposing axes following acute ischaemic stroke may provide an opportunity for protection of the neurovascular unit, particularly in the presence of pre-existing co-morbidities where the balance may be shifted. In the present review we will give an overview of the experimental stroke studies that have investigated pharmacological interventions of the RAS.",2016 Oct 7,"['Arroja, Mariana Moreira Coutinho', 'Reid, Emma', 'McCabe, Christopher']",Exp Transl Stroke Med,,,True
af6dacec0a1ba933a47d7451ef69ea06f7029882,PMC,Ability of device to collect bacteria from cough aerosols generated by adults with cystic fibrosis,http://dx.doi.org/10.12688/f1000research.9251.1,PMC5054809,27781088,CC BY,"Background: Identifying lung pathogens and acute spikes in lung counts remain a challenge in the treatment of patients with cystic fibrosis (CF). Bacteria from the deep lung may be sampled from aerosols produced during coughing. Methods: A new device was used to collect and measure bacteria levels from cough aerosols of patients with CF. Sputum and oral specimens were also collected and measured for comparison. Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus mitis were detected in specimens using Real-Time Polymerase Chain Reaction (RT-PCR) molecular assays. Results: Twenty adult patients with CF and 10 healthy controls participated. CF related bacteria (CFRB) were detected in 13/20 (65%) cough specimens versus 15/15 (100%) sputum specimens. Commensal S. mitis was present in 0/17 (0%, p=0.0002) cough specimens and 13/14 (93%) sputum samples. In normal controls, no bacteria were collected in cough specimens but 4/10 (40%) oral specimens were positive for CFRB. Conclusions: Non-invasive cough aerosol collection may detect lower respiratory pathogens in CF patients, with similar specificity and sensitivity to rates detected by BAL, without contamination by oral CFRB or commensal bacteria.",2016 Aug 5,"['Ku, David N.', 'Ku, Sarah K.', 'Helfman, Beth', 'McCarty, Nael A.', 'Wolff, Bernard J.', 'Winchell, Jonas M.', 'Anderson, Larry J.']",F1000Res,,,True
4f695bec496fb166d09c3377627d86cc587c2f27,PMC,Cathepsin L Helps to Defend Mice from Infection with Influenza A,http://dx.doi.org/10.1371/journal.pone.0164501,PMC5055332,27716790,CC0,"Host-derived proteases can augment or help to clear infections. This dichotomy is exemplified by cathepsin L (CTSL), which helps Hendra virus and SARS coronavirus to invade cells, but is essential for survival in mice with mycoplasma pneumonia. The present study tested the hypothesis that CTSL protects mice from serious consequences of infection by the orthomyxovirus influenza A, which is thought to be activated by host-supplied proteases other than CTSL. Ctsl(-/-) mice infected with influenza A/Puerto Rico/8/34(H1N1) had larger lung viral loads and higher mortality than infected Ctsl(+/+) mice. Lung inflammation in surviving infected mice peaked 14 days after initial infection, accompanied marked focal distal airway bronchiolization and epithelial metaplasia followed by desquamation and fibrotic interstitial remodeling, and persisted for at least 6 weeks. Most deaths occurred during the second week of infection in both groups of mice. In contrast to mycoplasma pneumonia, infiltrating cells were predominantly mononuclear rather than polymorphonuclear. The histopathology of lung inflammation and remodeling in survivors was similar in Ctsl(-/-) and Ctsl(+/+) mice, although Ctsl(+/+) mice cleared immunoreactive virus sooner. Furthermore, Ctsl(-/-) mice had profound deficits in CD4+ lymphocytes before and after infection and weaker production of pathogen-specific IgG. Thus, CTSL appears to support innate as well as adaptive responses, which confer a survival advantage on mice infected with the orthomyxovirus influenza A.",2016 Oct 7,"['Xu, Xiang', 'Greenland, John R.', 'Gotts, Jeffrey E.', 'Matthay, Michael A.', 'Caughey, George H.']",PLoS One,,,True
d8eb14ca18661130fdaf099482d6cd5b46032efe,PMC,"Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9), a biomarker for various pathological conditions, is produced in post-blood collection by fibrinolysis and coagulation factors",http://dx.doi.org/10.1186/s12014-016-9129-6,PMC5055723,27761105,CC BY,"BACKGROUND: Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9) is a new serum biomarker for chronic hepatitis that was discovered by proteomics analysis. Previous studies have shown that FIC5.9 is derived from the C-terminal region of fibrinogen alpha chain and the serum levels of FIC5.9 decrease in chronic hepatitis. It also have been reported that FIC5.9 cannot be detected in the blood stream of the systemic circulation and it is released from fibrinogen during blood clotting in collecting tube. However, the mechanism of FIC5.9 releasing from fibrinogen is unclear. METHODS: We formulated a hypothesis that FIC5.9 is released by enzymes that are activated by post-blood collection and may be coagulation and fibrinolysis factors. In this study, we analyzed the mechanisms of FIC5.9 releasing from fibrinogen in healthy blood. RESULTS: Our analysis showed that thrombin acts as an initiator for FIC5.9 releasing, and that mainly plasmin cleaves N-terminal end of FIC5.9 and neutrophil elastase cleave C-terminal end of FIC5.9. CONCLUSION: FIC5.9 reflects minute changes in coagulation and fibrinolysis factors and may be associated with pathological conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12014-016-9129-6) contains supplementary material, which is available to authorized users.",2016 Oct 7,"['Kikuchi, Wataru', 'Nishimura, Motoi', 'Kuga, Takahisa', 'Tsuchida, Sachio', 'Saito, Tatsuya', 'Satoh, Mamoru', 'Noda, Kenta', 'Kodera, Yoshio', 'Tomonaga, Takeshi', 'Nomura, Fumio']",Clin Proteomics,,,True
58a21f91c8d3c79e8be084088092f29dec2fc4d3,PMC,Genetic dissection of host immune response in pneumonia development and progression,http://dx.doi.org/10.1038/srep35021,PMC5057148,27725770,CC BY,"The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls). Experimental data were included in a series of 11 meta-analyses and eight subset analyses related to pneumonia susceptibility and outcome. TLR2 rs5743708 minor genotype appeared to be associated with CAP/Legionnaires’ disease/pneumococcal disease. In CAP patients, the IL6 rs1800795-C allele was associated with severe sepsis/septic shock/severe systemic inflammatory response, while the IL10 rs1800896-A allele protected against the development of these critical conditions. To contribute to deciphering of the above results, we performed an in silico analysis and a qualitative synthesis of literature data addressing basal and stimulated genotype-specific expression level. This data together with database information on transcription factors’ affinity changes caused by SNPs in putative promoter regions, the results of linkage disequilibrium analysis along with SNPs functional annotations supported assumptions about the complexity underlying the revealed associations.",2016 Oct 11,"['Smelaya, Tamara V.', 'Belopolskaya, Olesya B.', 'Smirnova, Svetlana V.', 'Kuzovlev, Artem N.', 'Moroz, Viktor V.', 'Golubev, Arkadiy M.', 'Pabalan, Noel A.', 'Salnikova, Lyubov E.']",Sci Rep,,,True
8764d0cec1713833f147b13fd476ae8fac42c600,PMC,Genetic dissection of host immune response in pneumonia development and progression,http://dx.doi.org/10.1038/srep35021,PMC5057148,27725770,CC BY,"The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls). Experimental data were included in a series of 11 meta-analyses and eight subset analyses related to pneumonia susceptibility and outcome. TLR2 rs5743708 minor genotype appeared to be associated with CAP/Legionnaires’ disease/pneumococcal disease. In CAP patients, the IL6 rs1800795-C allele was associated with severe sepsis/septic shock/severe systemic inflammatory response, while the IL10 rs1800896-A allele protected against the development of these critical conditions. To contribute to deciphering of the above results, we performed an in silico analysis and a qualitative synthesis of literature data addressing basal and stimulated genotype-specific expression level. This data together with database information on transcription factors’ affinity changes caused by SNPs in putative promoter regions, the results of linkage disequilibrium analysis along with SNPs functional annotations supported assumptions about the complexity underlying the revealed associations.",2016 Oct 11,"['Smelaya, Tamara V.', 'Belopolskaya, Olesya B.', 'Smirnova, Svetlana V.', 'Kuzovlev, Artem N.', 'Moroz, Viktor V.', 'Golubev, Arkadiy M.', 'Pabalan, Noel A.', 'Salnikova, Lyubov E.']",Sci Rep,,,True
27f21ae7789e41a6de01554cdae09cb93ef8524f,PMC,Epidemiological and pathological study of feline morbillivirus infection in domestic cats in Japan,http://dx.doi.org/10.1186/s12917-016-0853-y,PMC5057488,27724851,CC BY,"BACKGROUND: Feline morbillivirus (FmoPV) is a novel paramyxovirus found to infect domestic cats. FmoPV has been isolated in several countries in Asia and Europe and is considered to have genetic diversity. Also, it is suspected to be associated with feline renal diseases including tubulointerstitial nephritis (TIN), which affects domestic cats with a high incidence rate. RESULTS: To clarify the state of FmoPV infection among domestic cats in Japan, an epidemiological survey was conducted. Twenty-one out of 100 cats were found to have serum antibodies (Ab) against FmoPV-N protein by indirect immunofluorescence assay (IF) using FmoPV-N protein-expressing HeLa cells. Twenty-two of the cats were positive for FmoPV RNA in the urine and/or renal tissues. In total, 29 cats were positive for Ab and/or viral RNA. These FmoPV-infected cats were classified into three different phases of infection: RNA+/Ab + (14 cats), RNA+/Ab- (8 cats) and RNA-/Ab + (7 cats). In immunohistochemistry (IHC), 19 out of 29 cats were positive for FmoPV-N protein in kidney tissues; however, the FmoPV-N protein was located in the inflammatory lesions with severe grade in only four out of the 19 cats. Since 15 out of 29 infected cats were positive for viral RNA and Ab, approximately half of the infected cats were persistently infected with FmoPV. CONCLUSIONS: A statistically significant difference was observed between infection of FmoPV and the presence of inflammatory changes in renal lesions, indicating a relationship between FmoPV infection and feline renal diseases. However, we could not obtain histopathological evidence of a relationship between FmoPV infection and TIN.",2016 Oct 11,"['Park, Eun-Sil', 'Suzuki, Michio', 'Kimura, Masanobu', 'Mizutani, Hiroshi', 'Saito, Ryuichi', 'Kubota, Nami', 'Hasuike, Youko', 'Okajima, Jungo', 'Kasai, Hidemi', 'Sato, Yuko', 'Nakajima, Noriko', 'Maruyama, Keiji', 'Imaoka, Koichi', 'Morikawa, Shigeru']",BMC Vet Res,,,True
047a76d5e047a00728847bcdd162cb925486d0ab,PMC,A Computer-Aided Detection System for Digital Chest Radiographs,http://dx.doi.org/10.1155/2016/8208923,PMC5058572,27372536,CC BY,"Computer-aided detection systems aim at the automatic detection of diseases using different medical imaging modalities. In this paper, a novel approach to detecting normality/pathology in digital chest radiographs is proposed. The problem tackled is complicated since it is not focused on particular diseases but anything that differs from what is considered as normality. First, the areas of interest of the chest are found using template matching on the images. Then, a texture descriptor called local binary patterns (LBP) is computed for those areas. After that, LBP histograms are applied in a classifier algorithm, which produces the final normality/pathology decision. Our experimental results show the feasibility of the proposal, with success rates above 87% in the best cases. Moreover, our technique is able to locate the possible areas of pathology in nonnormal radiographs. Strengths and limitations of the proposed approach are described in the Conclusions.",2016 May 31,"['Carrillo-de-Gea, Juan Manuel', 'García-Mateos, Ginés', 'Fernández-Alemán, José Luis', 'Hernández-Hernández, José Luis']",J Healthc Eng,,,True
9cfaf4c8791d75c45d2d5c52a6e2da74363d2565,PMC,"Epidemiology, Co-Infections, and Outcomes of Viral Pneumonia in Adults: An Observational Cohort Study",http://dx.doi.org/10.1097/MD.0000000000002332,PMC5058945,26683973,CC BY,"Advanced technologies using polymerase-chain reaction have allowed for increased recognition of viral respiratory infections including pneumonia. Co-infections have been described for several respiratory viruses, especially with influenza. Outcomes of viral pneumonia, including cases with co-infections, have not been well described. This was observational cohort study conducted to describe hospitalized patients with viral pneumonia including co-infections, clinical outcomes, and predictors of mortality. Patients admitted from March 2013 to November 2014 with a positive respiratory virus panel (RVP) and radiographic findings of pneumonia within 48 h of the index RVP were included. Co-respiratory infection (CRI) was defined as any organism identification from a respiratory specimen within 3 days of the index RVP. Predictors of in-hospital mortality on univariate analysis were evaluated in a multivariate model. Of 284 patients with viral pneumonia, a majority (51.8%) were immunocompromised. A total of 84 patients (29.6%) were found to have a CRI with 48 (57.6%) having a bacterial CRI. Viral CRI with HSV, CMV, or both occurred in 28 patients (33.3%). Fungal (16.7%) and other CRIs (7.1%) were less common. Many patients required mechanical ventilation (54%) and vasopressor support (36%). Overall in-hospital mortality was high (23.2%) and readmissions were common with several patients re-hospitalized within 30 (21.1%) and 90 days (36.7%) of discharge. Predictors of in-hospital mortality on multivariate regression included severity of illness factors, stem-cell transplant, and identification of multiple respiratory viruses. In conclusion, hospital mortality is high among adult patients with viral pneumonia and patients with multiple respiratory viruses identified may be at a higher risk.",2015 Dec 18,"['Crotty, Matthew P.', 'Meyers, Shelby', 'Hampton, Nicholas', 'Bledsoe, Stephanie', 'Ritchie, David J.', 'Buller, Richard S.', 'Storch, Gregory A.', 'Micek, Scott T.', 'Kollef, Marin H.']",Medicine (Baltimore),,,True
e6515195e0fdd7f1fb437a01b8737685d6d92765,PMC,"Phylogenetic analysis of human rhinoviruses collected over four successive years in Sydney, Australia",http://dx.doi.org/10.1111/irv.12404,PMC5059946,27383422,CC BY,"BACKGROUND: Human rhinoviruses (HRV) cause a wide spectrum of disease, ranging from a mild influenza‐like illness (ILI) to severe respiratory infection. Molecular epidemiological data are limited for HRV circulating in the Southern Hemisphere. OBJECTIVES: To identify the species and genotypes of HRV from clinical samples collected in Sydney, Australia, from 2006 to 2009. METHODS: Combined nose and throat swabs or nasopharyngeal aspirates collected from individuals with ILI were tested for HRV using real‐time reverse‐transcriptase polymerase chain reaction (RT‐PCR). Sequencing data of 5′UTR and VP4/VP2 coding regions on RT‐PCR‐positive specimens were analysed. RESULTS: Human rhinoviruses were detected by real‐time PCR in 20.9% (116/555) of samples tested. Phylogenetic analysis of 5′UTR and VP4/VP2 on HRV‐positive samples was concordant in the grouping of HRV A and B species but not HRV C species. Eighty per cent (16/20) of sequences that grouped as HRV C in the VP4/VP2 tree clustered as HRV A, alongside some previously described C strains as subspecies C/A. Discordant branching was seen within HRV A group: two sequences clustering as A in the VP4/VP2 tree branched within the C/A subspecies in the 5′UTR tree, and one sequence showed identity to different HRV A strains in the two genes. The prevalence of HRV C and C/A species was greater in paediatric compared to adult patients (47.9% vs 25.5%, P = .032). CONCLUSION: Human rhinoviruses are a common cause of respiratory infections, and HRV C is present in the Southern Hemisphere. Sequencing of multiple HRV regions may be necessary to determine exact phylogenetic relationships.",2016 Nov 9,"['Ratnamohan, Vigneswary M.', 'Zeng, Frank', 'Donovan, Linda', 'MacIntyre, Chandini R.', 'Kok, Jen', 'Dwyer, Dominic E.']",Influenza Other Respir Viruses,,,True
8688ca00892a6134485b2d9dd30f95e7aad1a3d8,PMC,"Expatriates’ Multiple Fears, from Terrorism to Working Conditions: Development of a Model",http://dx.doi.org/10.3389/fpsyg.2016.01571,PMC5062027,27790173,CC BY,"Companies’ internationalization appears to be fundamental in the current globalized and competitive environment and seems important not only for organizational success, but also for societal development and sustainability. On one hand, global business increases the demand for managers for international assignment. On the other hand, emergent fears, such as terrorism, seem to be developing around the world, enhancing the risk of expatriates’ potential health problems. The purpose of this paper is to examine the relationships between the emergent concept of fear of expatriation with further workplace fears (economic crisis and dangerous working conditions) and with mental health problems. The study uses a quantitative design. Self-reported data were collected from 265 Italian expatriate workers assigned to both Italian and worldwide projects. Structural equation model analyses showed that fear of expatriation mediates the relationship of mental health with fear of economic crisis and with perceived dangerous working conditions. As expected, in addition to fear, worries of expatriation are also related to further fears. Although, the study is based on self-reports and the cross-sectional study design limits the possibility of making causal inferences, the new constructs introduced add to previous research.",2016 Oct 13,"['Giorgi, Gabriele', 'Montani, Francesco', 'Fiz-Perez, Javier', 'Arcangeli, Giulio', 'Mucci, Nicola']",Front Psychol,,,True
65c8138a4905491ab3bcd6aa58320408abecc9e7,PMC,Identification of Novel Rosavirus Species That Infects Diverse Rodent Species and Causes Multisystemic Dissemination in Mouse Model,http://dx.doi.org/10.1371/journal.ppat.1005911,PMC5063349,27737017,CC BY,"While novel picornaviruses are being discovered in rodents, their host range and pathogenicity are largely unknown. We identified two novel picornaviruses, rosavirus B from the street rat, Norway rat, and rosavirus C from five different wild rat species (chestnut spiny rat, greater bandicoot rat, Indochinese forest rat, roof rat and Coxing's white-bellied rat) in China. Analysis of 13 complete genome sequences showed that “Rosavirus B” and “Rosavirus C” represent two potentially novel picornavirus species infecting different rodents. Though being most closely related to rosavirus A, rosavirus B and C possessed distinct protease cleavage sites and variations in Yn-Xm-AUG sequence in 5’UTR and myristylation site in VP4. Anti-rosavirus B VP1 antibodies were detected in Norway rats, whereas anti-rosavirus C VP1 and neutralizing antibodies were detected in Indochinese forest rats and Coxing's white-bellied rats. While the highest prevalence was observed in Coxing's white-bellied rats by RT-PCR, the detection of rosavirus C from different rat species suggests potential interspecies transmission. Rosavirus C isolated from 3T3 cells causes multisystemic diseases in a mouse model, with high viral loads and positive viral antigen expression in organs of infected mice after oral or intracerebral inoculation. Histological examination revealed alveolar fluid exudation, interstitial infiltration, alveolar fluid exudate and wall thickening in lungs, and hepatocyte degeneration and lymphocytic/monocytic inflammatory infiltrates with giant cell formation in liver sections of sacrificed mice. Since rosavirus A2 has been detected in fecal samples of children, further studies should elucidate the pathogenicity and emergence potential of different rosaviruses.",2016 Oct 13,"['Lau, Susanna K. P.', 'Woo, Patrick C. Y.', 'Li, Kenneth S. M.', 'Zhang, Hao-Ji', 'Fan, Rachel Y. Y.', 'Zhang, Anna J. X.', 'Chan, Brandon C. C.', 'Lam, Carol S. F.', 'Yip, Cyril C. Y.', 'Yuen, Ming-Chi', 'Chan, Kwok-Hung', 'Chen, Zhi-Wei', 'Yuen, Kwok-Yung']",PLoS Pathog,,,True
83ee38f0c4d9191d4f6cad59de96a20a50c18417,PMC,Complete Genome Sequence of a Brazil-Type Avian coronavirus Detected in a Chicken,http://dx.doi.org/10.1128/genomeA.01135-16,PMC5064116,27738043,CC BY,"Avian coronavirus is the causative agent of infectious bronchitis in chickens, leading to multisystemic disease that might be controlled if adequate vaccine strains are used. This paper reports the first complete genome sequence of a Brazil type of this virus (27,615 nucleotides [nt]) isolated from the kidneys of a chicken.",2016 Oct 13,"['Brandão, Paulo E.', 'Ayres, Giselle R. R.', 'Torres, Carolina A.', 'Villarreal, Laura Y. B.', 'Hora, Aline S.', 'Taniwaki, Sueli A.']",Genome Announc,,,True
6c4acd1676d614bf6b2e4fdf9d17337e237d440d,PMC,Respiratory Illness and Allergy Related to Work and Home Environment among Commercial Pilots,http://dx.doi.org/10.1371/journal.pone.0164954,PMC5065138,27741314,CC BY,"The aim was to study associations between work and home environment and prevalence and incidence of respiratory health and a history of atopy in a 3-y cohort of commercial pilots. A questionnaire was mailed in 1997 to all pilots in a Scandinavian airline company (N = 622); 577 (93%) participated. The same questionnaire was sent to the participants 3 years later, 436 participated (76%). There were questions on asthma, respiratory symptoms and infections, allergies, the cabin environment, psychosocial environment and the home environment. Associations were analyzed by multiple logistic regression, calculating odds ratios (OR) with 95% confidence intervals (95%CI). The incidence of doctors’ diagnosed asthma and atopy were 2.4 and 16.6 per 1000 person years, respectively. Pilots changing type of flight during follow-up got more airway infections (OR = 11.27; 95% CI 2.39–53.14). Those reporting decreased work control (OR = 1.85; 95% CI 1.03–3.31 for 1 unit change) and those with environmental tobacco smoke (ETS) at home (OR = 3.73; 95% CI 1.09–12.83) had a higher incidence of atopy during follow up. Dampness or mould at home was associated with a higher prevalence of asthma symptoms (OR = 3.55; 95% CI 1.43–8.82) and airway infections (OR = 3.12 95% CI 1.27–7.68). Window pane condensation in winter at home, reported at baseline, was associated with increased incidence of asthma symptoms (OR = 4.14; 95% CI 1.32–12.97) and pilots living in newer buildings at baseline had a higher incidence of airway infections (OR = 5.23; 95% CI 1.43–19.10). In conclusion, lack of work control and ETS at home can be a risk factors for development of allergic symptoms in pilots. Window pane condensation at home can be a risk factor for incidence of asthma symptoms. Dampness and mould at home can be a risk factor for prevalence of asthma symptoms and airway infections and living in newer buildings can be a risk factor for incidence of airway infections.",2016 Oct 14,"['Fu, Xi', 'Lindgren, Torsten', 'Wieslander, Gunilla', 'Janson, Christer', 'Norbäck, Dan']",PLoS One,,,True
e99a0adb1aa26558acfc74fa0c7197a8a591b6ef,PMC,Pathogenicity of a TW-Like Strain of Infectious Bronchitis Virus and Evaluation of the Protection Induced against It by a QX-Like Strain,http://dx.doi.org/10.3389/fmicb.2016.01653,PMC5067408,27803698,CC BY,"Avian infectious bronchitis, a highly contagious disease caused by avian infectious bronchitis virus (IBV), is of considerable economic importance to the poultry industry. New IBV TW-like strains have increasingly emerged in China in recent years; hence, evaluating their pathogenicity and developing a specific vaccine to guard against their potential threat to the poultry industry is important. Here, we examined the pathogenicity of a TW-like IBV strain (GD), and evaluated the protective efficacy of the QX-like strain (JS) against GD in challenge infections in chickens. The results revealed that strain-GD-infected birds experienced severe respiratory signs, renal lesions, and 30–40% mortality. The GD virus had extensive tissue tropism, especially in the trachea, lungs, kidneys, and bursa of Fabricius, and was continuously shed via the respiratory tract and cloaca. The QX-like IBV strain JS is able to completely protect chickens from challenge with the TW-like IBV GD field strain, with no clinical signs or gross lesions, decreased tissue replication rates, lower ciliostasis score, and reduced virus shedding. These findings indicate that IBV GD is highly virulent, and that QX-like JS may serve as an effective vaccine against the threat posed by IBV TW-like viruses.",2016 Oct 18,"['Yan, Shi-hong', 'Chen, Yang', 'Zhao, Jing', 'Xu, Gang', 'Zhao, Ye', 'Zhang, Guo-zhong']",Front Microbiol,,,True
4315ae43f201739bb56193e328dfdbd8a6646b4b,PMC,A Disintegrin and Metalloprotease 17 in the Cardiovascular and Central Nervous Systems,http://dx.doi.org/10.3389/fphys.2016.00469,PMC5067531,27803674,CC BY,"ADAM17 is a metalloprotease and disintegrin that lodges in the plasmatic membrane of several cell types and is able to cleave a wide variety of cell surface proteins. It is somatically expressed in mammalian organisms and its proteolytic action influences several physiological and pathological processes. This review focuses on the structure of ADAM17, its signaling in the cardiovascular system and its participation in certain disorders involving the heart, blood vessels, and neural regulation of autonomic and cardiovascular modulation.",2016 Oct 18,"['Xu, Jiaxi', 'Mukerjee, Snigdha', 'Silva-Alves, Cristiane R. A.', 'Carvalho-Galvão, Alynne', 'Cruz, Josiane C.', 'Balarini, Camille M.', 'Braga, Valdir A.', 'Lazartigues, Eric', 'França-Silva, Maria S.']",Front Physiol,,,True
5e1e254fc92ef00d3a23ebaab664289a8a58c88a,PMC,Viral fusion efficacy of specific H3N2 influenza virus reassortant combinations at single-particle level,http://dx.doi.org/10.1038/srep35537,PMC5067655,27752100,CC BY,"Virus pseudotyping is a useful and safe technique for studying entry of emerging strains of influenza virus. However, few studies have compared different reassortant combinations in pseudoparticle systems, or compared entry kinetics of native viruses and their pseudotyped analogs. Here, vesicular stomatitis virus (VSV)-based pseudovirions displaying distinct influenza virus envelope proteins were tested for fusion activity. We produced VSV pseudotypes containing the prototypical X-31 (H3) HA, either alone or with strain-matched or mismatched N2 NAs. We performed single-particle fusion assays using total internal reflection fluorescence microscopy to compare hemifusion kinetics among these pairings. Results illustrate that matching pseudoparticles behaved very similarly to native virus. Pseudoparticles harboring mismatched HA-NA pairings fuse at significantly slower rates than native virus, and NA-lacking pseudoparticles exhibiting the slowest fusion rates. Relative viral membrane HA density of matching pseudoparticles was higher than in mismatching or NA-lacking pseudoparticles. An equivalent trend of HA expression level on cell membranes of HA/NA co-transfected cells was observed and intracellular trafficking of HA was affected by NA co-expression. Overall, we show that specific influenza HA-NA combinations can profoundly affect the critical role played by HA during entry, which may factor into viral fitness and the emergence of new pandemic influenza viruses.",2016 Oct 18,"['Hsu, Hung-Lun', 'Millet, Jean K.', 'Costello, Deirdre A.', 'Whittaker, Gary R.', 'Daniel, Susan']",Sci Rep,,,True
d106a3d8a3290e403a4b0d22c22698e3d609809d,PMC,Day-to-Day Population Movement and the Management of Dengue Epidemics,http://dx.doi.org/10.1007/s11538-016-0209-6,PMC5069346,27704330,CC BY,"Dengue is a growing public health problem in tropical and subtropical cities. It is transmitted by mosquitoes, and the main strategy for epidemic prevention and control is insecticide fumigation. Effective management is, however, proving elusive. People’s day-to-day movement about the city is believed to be an important factor in the epidemiological dynamics. We use a simple model to examine the fundamental roles of broad demographic and spatial structures in epidemic initiation, growth and control. We show that the key factors are local dilution, characterised by the vector–host ratio, and spatial connectivity, characterised by the extent of habitually variable movement patterns. Epidemic risk in the population is driven by the demographic groups that frequent the areas with the highest vector–host ratio, even if they only spend some of their time there. Synchronisation of epidemic trajectories in different demographic groups is governed by the vector–host ratios to which they are exposed and the strength of connectivity. Strategies for epidemic prevention and management may be made more effective if they take into account the fluctuating landscape of transmission intensity associated with spatial heterogeneity in the vector–host ratio and people’s day-to-day movement patterns. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11538-016-0209-6) contains supplementary material, which is available to authorized users.",2016 Oct 4,"['Falcón-Lezama, Jorge A.', 'Martínez-Vega, Ruth A.', 'Kuri-Morales, Pablo A.', 'Ramos-Castañeda, José', 'Adams, Ben']",Bull Math Biol,,,False
5c5236506e7dfce0f35caf94d9eec62c5b815d0d,PMC,Day-to-Day Population Movement and the Management of Dengue Epidemics,http://dx.doi.org/10.1007/s11538-016-0209-6,PMC5069346,27704330,CC BY,"Dengue is a growing public health problem in tropical and subtropical cities. It is transmitted by mosquitoes, and the main strategy for epidemic prevention and control is insecticide fumigation. Effective management is, however, proving elusive. People’s day-to-day movement about the city is believed to be an important factor in the epidemiological dynamics. We use a simple model to examine the fundamental roles of broad demographic and spatial structures in epidemic initiation, growth and control. We show that the key factors are local dilution, characterised by the vector–host ratio, and spatial connectivity, characterised by the extent of habitually variable movement patterns. Epidemic risk in the population is driven by the demographic groups that frequent the areas with the highest vector–host ratio, even if they only spend some of their time there. Synchronisation of epidemic trajectories in different demographic groups is governed by the vector–host ratios to which they are exposed and the strength of connectivity. Strategies for epidemic prevention and management may be made more effective if they take into account the fluctuating landscape of transmission intensity associated with spatial heterogeneity in the vector–host ratio and people’s day-to-day movement patterns. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11538-016-0209-6) contains supplementary material, which is available to authorized users.",2016 Oct 4,"['Falcón-Lezama, Jorge A.', 'Martínez-Vega, Ruth A.', 'Kuri-Morales, Pablo A.', 'Ramos-Castañeda, José', 'Adams, Ben']",Bull Math Biol,,,True
dfc76bec0889529fc8cfd5075db5b638ee8cefbc,PMC,Gene-expression reversal of lncRNAs and associated mRNAs expression in active vs latent HIV infection,http://dx.doi.org/10.1038/srep34862,PMC5069461,27756902,CC BY,"Interplay between lncRNAs and mRNAs is rapidly emerging as a key epigenetic mechanism in controlling various cell functions. HIV can actively infect and/or can persist latently for years by manipulating host epigenetics; however, its molecular essence remains undiscovered in entirety. Here for the first time, we delineate the influence of HIV on global lncRNAs expression in monocytic cells lines. Our analysis revealed the expression modulation of nearly 1060 such lncRNAs which are associated with differentially expressed mRNAs in active and latent infection. This suggests a greater role of lncRNAs in regulating transcriptional and post-transcriptional gene expression during HIV infection. The differentially expressed mRNAs were involved in several different biological pathways where immunological networks were most enriched. Importantly, we discovered that HIV induces expression reversal of more than 150 lncRNAs between its active and latent infection. Also, hundreds of unique lncRNAs were identified in both infection conditions. The pathology specific “gene-expression reversal” and “on-and-off” switching of lncRNAs and associated mRNAs may lead to establish the relationship between active and HIV infection.",2016 Oct 19,"['Nair, Madhavan', 'Sagar, Vidya', 'Pilakka-Kanthikeel, Sudheesh']",Sci Rep,,,True
7639ac8f8d44510f623a49b4154324b51b0d07fd,PMC,Gene-expression reversal of lncRNAs and associated mRNAs expression in active vs latent HIV infection,http://dx.doi.org/10.1038/srep34862,PMC5069461,27756902,CC BY,"Interplay between lncRNAs and mRNAs is rapidly emerging as a key epigenetic mechanism in controlling various cell functions. HIV can actively infect and/or can persist latently for years by manipulating host epigenetics; however, its molecular essence remains undiscovered in entirety. Here for the first time, we delineate the influence of HIV on global lncRNAs expression in monocytic cells lines. Our analysis revealed the expression modulation of nearly 1060 such lncRNAs which are associated with differentially expressed mRNAs in active and latent infection. This suggests a greater role of lncRNAs in regulating transcriptional and post-transcriptional gene expression during HIV infection. The differentially expressed mRNAs were involved in several different biological pathways where immunological networks were most enriched. Importantly, we discovered that HIV induces expression reversal of more than 150 lncRNAs between its active and latent infection. Also, hundreds of unique lncRNAs were identified in both infection conditions. The pathology specific “gene-expression reversal” and “on-and-off” switching of lncRNAs and associated mRNAs may lead to establish the relationship between active and HIV infection.",2016 Oct 19,"['Nair, Madhavan', 'Sagar, Vidya', 'Pilakka-Kanthikeel, Sudheesh']",Sci Rep,,,False
7694cd45d861b0363acf826f1ccb83b0f5a40e4c,PMC,"MPLEx: a Robust and Universal Protocol for Single-Sample Integrative Proteomic, Metabolomic, and Lipidomic Analyses",http://dx.doi.org/10.1128/mSystems.00043-16,PMC5069757,27822525,CC BY,"Integrative multi-omics analyses can empower more effective investigation and complete understanding of complex biological systems. Despite recent advances in a range of omics analyses, multi-omic measurements of the same sample are still challenging and current methods have not been well evaluated in terms of reproducibility and broad applicability. Here we adapted a solvent-based method, widely applied for extracting lipids and metabolites, to add proteomics to mass spectrometry-based multi-omics measurements. The metabolite, protein, and lipid extraction (MPLEx) protocol proved to be robust and applicable to a diverse set of sample types, including cell cultures, microbial communities, and tissues. To illustrate the utility of this protocol, an integrative multi-omics analysis was performed using a lung epithelial cell line infected with Middle East respiratory syndrome coronavirus, which showed the impact of this virus on the host glycolytic pathway and also suggested a role for lipids during infection. The MPLEx method is a simple, fast, and robust protocol that can be applied for integrative multi-omic measurements from diverse sample types (e.g., environmental, in vitro, and clinical). IMPORTANCE In systems biology studies, the integration of multiple omics measurements (i.e., genomics, transcriptomics, proteomics, metabolomics, and lipidomics) has been shown to provide a more complete and informative view of biological pathways. Thus, the prospect of extracting different types of molecules (e.g., DNAs, RNAs, proteins, and metabolites) and performing multiple omics measurements on single samples is very attractive, but such studies are challenging due to the fact that the extraction conditions differ according to the molecule type. Here, we adapted an organic solvent-based extraction method that demonstrated broad applicability and robustness, which enabled comprehensive proteomics, metabolomics, and lipidomics analyses from the same sample. Author Video: An author video summary of this article is available.",2016 May 10,"['Nakayasu, Ernesto S.', 'Nicora, Carrie D.', 'Sims, Amy C.', 'Burnum-Johnson, Kristin E.', 'Kim, Young-Mo', 'Kyle, Jennifer E.', 'Matzke, Melissa M.', 'Shukla, Anil K.', 'Chu, Rosalie K.', 'Schepmoes, Athena A.', 'Jacobs, Jon M.', 'Baric, Ralph S.', 'Webb-Robertson, Bobbie-Jo', 'Smith, Richard D.', 'Metz, Thomas O.']",mSystems,,,True
ad724f7660b9d84da71a1855f411b5a450aa309e,PMC,A Universal Next-Generation Sequencing Protocol To Generate Noninfectious Barcoded cDNA Libraries from High-Containment RNA Viruses,http://dx.doi.org/10.1128/mSystems.00039-15,PMC5069770,27822536,CC BY,"Several biosafety level 3 and/or 4 (BSL-3/4) pathogens are high-consequence, single-stranded RNA viruses, and their genomes, when introduced into permissive cells, are infectious. Moreover, many of these viruses are select agents (SAs), and their genomes are also considered SAs. For this reason, cDNAs and/or their derivatives must be tested to ensure the absence of infectious virus and/or viral RNA before transfer out of the BSL-3/4 and/or SA laboratory. This tremendously limits the capacity to conduct viral genomic research, particularly the application of next-generation sequencing (NGS). Here, we present a sequence-independent method to rapidly amplify viral genomic RNA while simultaneously abolishing both viral and genomic RNA infectivity across multiple single-stranded positive-sense RNA (ssRNA+) virus families. The process generates barcoded DNA amplicons that range in length from 300 to 1,000 bp, which cannot be used to rescue a virus and are stable to transport at room temperature. Our barcoding approach allows for up to 288 barcoded samples to be pooled into a single library and run across various NGS platforms without potential reconstitution of the viral genome. Our data demonstrate that this approach provides full-length genomic sequence information not only from high-titer virion preparations but it can also recover specific viral sequence from samples with limited starting material in the background of cellular RNA, and it can be used to identify pathogens from unknown samples. In summary, we describe a rapid, universal standard operating procedure that generates high-quality NGS libraries free of infectious virus and infectious viral RNA. IMPORTANCE This report establishes and validates a standard operating procedure (SOP) for select agents (SAs) and other biosafety level 3 and/or 4 (BSL-3/4) RNA viruses to rapidly generate noninfectious, barcoded cDNA amenable for next-generation sequencing (NGS). This eliminates the burden of testing all processed samples derived from high-consequence pathogens prior to transfer from high-containment laboratories to lower-containment facilities for sequencing. Our established protocol can be scaled up for high-throughput sequencing of hundreds of samples simultaneously, which can dramatically reduce the cost and effort required for NGS library construction. NGS data from this SOP can provide complete genome coverage from viral stocks and can also detect virus-specific reads from limited starting material. Our data suggest that the procedure can be implemented and easily validated by institutional biosafety committees across research laboratories.",2016 Jun 7,"['Moser, Lindsey A.', 'Ramirez-Carvajal, Lisbeth', 'Puri, Vinita', 'Pauszek, Steven J.', 'Matthews, Krystal', 'Dilley, Kari A.', 'Mullan, Clancy', 'McGraw, Jennifer', 'Khayat, Michael', 'Beeri, Karen', 'Yee, Anthony', 'Dugan, Vivien', 'Heise, Mark T.', 'Frieman, Matthew B.', 'Rodriguez, Luis L.', 'Bernard, Kristen A.', 'Wentworth, David E.', 'Stockwell, Timothy B.', 'Shabman, Reed S.']",mSystems,,,True
4350c7bc82bb4dba102fe29a6b50ed632b28a920,PMC,What Have We Learned about the Microbiomes of Indoor Environments?,http://dx.doi.org/10.1128/mSystems.00083-16,PMC5069963,27822547,CC BY,"The advent and application of high-throughput molecular techniques for analyzing microbial communities in the indoor environment have led to illuminating findings and are beginning to change the way we think about human health in relation to the built environment. Here I review recent studies on the microbiology of the built environment, organize their findings into 12 major thematic categories, and comment on how these studies have or have not advanced knowledge in each area beyond what we already knew from over 100 years of applying culture-based methods to building samples. I propose that while we have added tremendous complexity to the rich existing knowledge base, the practical implications of this added complexity remain somewhat elusive. It remains to be seen how this new knowledge base will change how we design, build, and operate buildings. Much more research is needed to better understand the complexity with which indoor microbiomes may affect human health in both positive and negative ways.",2016 Jul 26,"Stephens, Brent",mSystems,,,True
92f5ed730f359773e8b3af4bca2d6d6b9cc224c9,PMC,A quasi-experimental study to determine the effects of a multifaceted educational intervention on hand hygiene compliance in a radiography unit,http://dx.doi.org/10.1186/s13756-016-0133-4,PMC5070356,27777757,CC BY,"BACKGROUND: Whilst numerous studies have investigated nurses’ compliance with hand hygiene and use of alcohol-based hand rub (ABHR), limited attention has been paid to these issues in allied health staff. Reports have linked infections to breaches in infection control in the radiography unit (RU). With advances in medical imaging, a higher proportion of patients come into contact with RU staff increasing the need for good hand hygiene compliance. This study aimed to evaluate effectiveness on compliance of an intervention to improve awareness of hand hygiene in the RU of a district hospital. METHODS: A quasi-experimental study design including questionnaires assessing knowledge and attitudes of hand hygiene and direct observation of participants was used to evaluate an educational programme on hand hygiene of the RU of a large district hospital. All healthcare workers (HCW), comprising 76 radiographers, 17 nurses, and nine healthcare assistants (HCA), agreed to participate in the study. Of these, 85 completed the initial and 76 the post-test anonymous questionnaire. The hand hygiene compliance of all 102 HCW was observed over a 3-week period prior to and after the intervention. The 2-month intervention consisted of talks on hand hygiene and benefits of ABHR, provision of visual aids, wall-mounted ABHR dispensers, and personal bottles of ABHR. RESULTS: Before the intervention, overall hand hygiene compliance was low (28.9 %). Post-intervention, compliance with hand hygiene increased to 51.4 %. This improvement was significant for radiographers and HCA. Additionally, knowledge and attitudes improved in particular, understanding that ABHR can largely replace handwashing and there is a need to perform hand hygiene after environmental contact. The increased use of ABHR allowed HCW to feel they had enough time to perform hand hygiene. CONCLUSIONS: The educational intervention led to increased awareness of hand hygiene opportunities and better acceptance of ABHR use. The reduced time needed to perform hand rubbing and improved access to dispensers resulted in fewer missed opportunities. Although radiographers and other allied HCW make frequent contact with patients, these may be mistakenly construed as irrelevant with respect to healthcare associated infections. Stronger emphasis on hand hygiene compliance of these staff may help reduce infection risk.",2016 Oct 19,"['O’Donoghue, Margaret', 'Ng, Suk-Hing', 'Suen, Lorna KP', 'Boost, Maureen']",Antimicrob Resist Infect Control,,,True
c25889c8a5469237f3437394d9c595f9af0c7c4c,PMC,Identification of Aedes aegypti Long Intergenic Non-coding RNAs and Their Association with Wolbachia and Dengue Virus Infection,http://dx.doi.org/10.1371/journal.pntd.0005069,PMC5070814,27760142,CC BY,"Long intergenic non-coding RNAs (lincRNAs) are appearing as an important class of regulatory RNAs with a variety of biological functions. The aim of this study was to identify the lincRNA profile in the dengue vector Aedes aegypti and evaluate their potential role in host-pathogen interaction. The majority of previous RNA-Seq transcriptome studies in Ae. aegypti have focused on the expression pattern of annotated protein coding genes under different biological conditions. Here, we used 35 publically available RNA-Seq datasets with relatively high depth to screen the Ae. aegypti genome for lincRNA discovery. This led to the identification of 3,482 putative lincRNAs. These lincRNA genes displayed a slightly lower GC content and shorter transcript lengths compared to protein-encoding genes. Ae. aegypti lincRNAs also demonstrate low evolutionary sequence conservation even among closely related species such as Culex quinquefasciatus and Anopheles gambiae. We examined their expression in dengue virus serotype 2 (DENV-2) and Wolbachia infected and non-infected adult mosquitoes and Aa20 cells. The results revealed that DENV-2 infection increased the abundance of a number of host lincRNAs, from which some suppress viral replication in mosquito cells. RNAi-mediated silencing of lincRNA_1317 led to enhancement in viral replication, which possibly indicates its potential involvement in the host anti-viral defense. A number of lincRNAs were also differentially expressed in Wolbachia-infected mosquitoes. The results will facilitate future studies to unravel the function of lncRNAs in insects and may prove to be beneficial in developing new ways to control vectors or inhibit replication of viruses in them.",2016 Oct 19,"['Etebari, Kayvan', 'Asad, Sultan', 'Zhang, Guangmei', 'Asgari, Sassan']",PLoS Negl Trop Dis,,,True
ac1e0c34f47a58c5d830bd63399b3400cab8375d,PMC,Characterization of the Role of Hexamer AGUAAA and Poly(A) Tail in Coronavirus Polyadenylation,http://dx.doi.org/10.1371/journal.pone.0165077,PMC5070815,27760233,CC BY,"Similar to eukaryotic mRNA, the positive-strand coronavirus genome of ~30 kilobases is 5’-capped and 3’-polyadenylated. It has been demonstrated that the length of the coronaviral poly(A) tail is not static but regulated during infection; however, little is known regarding the factors involved in coronaviral polyadenylation and its regulation. Here, we show that during infection, the level of coronavirus poly(A) tail lengthening depends on the initial length upon infection and that the minimum length to initiate lengthening may lie between 5 and 9 nucleotides. By mutagenesis analysis, it was found that (i) the hexamer AGUAAA and poly(A) tail are two important elements responsible for synthesis of the coronavirus poly(A) tail and may function in concert to accomplish polyadenylation and (ii) the function of the hexamer AGUAAA in coronaviral polyadenylation is position dependent. Based on these findings, we propose a process for how the coronaviral poly(A) tail is synthesized and undergoes variation. Our results provide the first genetic evidence to gain insight into coronaviral polyadenylation.",2016 Oct 19,"['Peng, Yu-Hui', 'Lin, Ching-Houng', 'Lin, Chao-Nan', 'Lo, Chen-Yu', 'Tsai, Tsung-Lin', 'Wu, Hung-Yi']",PLoS One,,,True
60af5c4467ebb43ff79857a9c515e625d4aa3aa9,PMC,Cryo-electron Microscopy Analysis of Structurally Heterogeneous Macromolecular Complexes,http://dx.doi.org/10.1016/j.csbj.2016.10.002,PMC5072154,27800126,CC BY,"Cryo-electron microscopy (cryo-EM) has for a long time been a technique of choice for determining structure of large and flexible macromolecular complexes that were difficult to study by other experimental techniques such as X-ray crystallography or nuclear magnetic resonance. However, a fast development of instruments and software for cryo-EM in the last decade has allowed that a large range of complexes can be studied by cryo-EM, and that their structures can be obtained at near-atomic resolution, including the structures of small complexes (e.g., membrane proteins) whose size was earlier an obstacle to cryo-EM. Image analysis to identify multiple coexisting structures in the same specimen (multiconformation reconstruction) is now routinely done both to solve structures at near-atomic resolution and to study conformational dynamics. Methods for multiconformation reconstruction and latest examples of their applications are the focus of this review.",2016 Oct 14,"Jonić, Slavica",Comput Struct Biotechnol J,,,False
188a2e1351ceae0aa8347e1a1d7af1e3b7b66a02,PMC,Epidemiology and Clinical Presentations of Respiratory Syncytial Virus Subgroups A and B Detected with Multiplex Real-Time PCR,http://dx.doi.org/10.1371/journal.pone.0165108,PMC5072546,27764220,CC BY,"Respiratory syncytial virus (RSV) is one of the most important pathogenic infections of children and requires in-depth research worldwide, and especially in developing countries. We used a novel multiplex real-time PCR to test 5483 patients (≤ 14 years old) hospitalized with respiratory illness in Guangzhou, China, over a 3-year period. Of these patients, 729 were positive for RSV-A (51.2%, 373/729) or RSV-B (48.8%, 356/729), but none was infected with both viruses. Two seasonal peaks in total RSV were detected at the changes from winter to spring and from summer to autumn. RSV-B was dominant in 2013 and RSV-A in 2015, whereas RSV-A and RSV-B cocirculated in 2014. The clinical presentations of 645 RSV-positive patients were analyzed. Bronchiolitis, dyspnea, coryza, vomiting, poor appetite, and diarrhea occurred more frequently in RSV-A-positive than RSV-B-positive patients, whereas chill, headache, myalgia, debility, and rash etc. were more frequent in RSV-B-positive than RSV-A-positive patients, suggesting specific clinical characteristics for RSV-A and RSV-B. Coinfectons with other pathogens were common and diverse. Bronchiolitis, fever (≥ 38°C), and poor appetite were more frequent in patients with single RSV infections than in coinfected patients, suggesting the key pathogenic activity of RSV. Analysis of the relationships between the comparative viral load and clinical presentations showed significant differences in bronchiolitis, fever (≥ 38°C), and rash etc. among patients with different viral loads. This study provides a novel rapid method for detecting RSV subgroups, and provides new insights into the epidemiology and clinical implications of RSV.",2016 Oct 20,"['Liu, Wenkuan', 'Chen, Dehui', 'Tan, Weiping', 'Xu, Duo', 'Qiu, Shuyan', 'Zeng, Zhiqi', 'Li, Xiao', 'Zhou, Rong']",PLoS One,,,True
cbabbd687725e949c99a0a6f53f033128ea1aaca,PMC,Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses,http://dx.doi.org/10.1371/journal.pntd.0005071,PMC5072622,27764114,CC BY,"Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes. Instead of using whole-virus formulations, we are exploring the potentials for a particulate subunit vaccine, based on DENV E-protein displayed on nanoparticles that have been precisely molded using Particle Replication in Non-wetting Template (PRINT) technology. Here we describe immunization studies with a DENV2-nanoparticle vaccine candidate. The ectodomain of DENV2-E protein was expressed as a secreted recombinant protein (sRecE), purified and adsorbed to poly (lactic-co-glycolic acid) (PLGA) nanoparticles of different sizes and shape. We show that PRINT nanoparticle adsorbed sRecE without any adjuvant induces higher IgG titers and a more potent DENV2-specific neutralizing antibody response compared to the soluble sRecE protein alone. Antigen trafficking indicate that PRINT nanoparticle display of sRecE prolongs the bio-availability of the antigen in the draining lymph nodes by creating an antigen depot. Our results demonstrate that PRINT nanoparticles are a promising platform for delivering subunit vaccines against flaviviruses such as dengue and Zika.",2016 Oct 20,"['Metz, Stefan W.', 'Tian, Shaomin', 'Hoekstra, Gabriel', 'Yi, Xianwen', 'Stone, Michelle', 'Horvath, Katie', 'Miley, Michael J.', 'DeSimone, Joseph', 'Luft, Chris J.', 'de Silva, Aravinda M.']",PLoS Negl Trop Dis,,,True
11ccc8d0c6d5b3297821a0e39535ce9dcb4810ef,PMC,A Meta-Analysis of the Association between Gender and Protective Behaviors in Response to Respiratory Epidemics and Pandemics,http://dx.doi.org/10.1371/journal.pone.0164541,PMC5074573,27768704,CC0,"Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society. The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread. Health-protective behaviors take several forms. Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport). Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions. Understanding the determinants of the public’s behavioral response is crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread. While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response. The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors. Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors. It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship. These results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases. This information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.",2016 Oct 21,"['Moran, Kelly R.', 'Del Valle, Sara Y.']",PLoS One,,,True
70f13cba6028d0822b98cc2d8e5bd221ea8d4e16,PMC,A Meta-Analysis of the Association between Gender and Protective Behaviors in Response to Respiratory Epidemics and Pandemics,http://dx.doi.org/10.1371/journal.pone.0164541,PMC5074573,27768704,CC0,"Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society. The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread. Health-protective behaviors take several forms. Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport). Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions. Understanding the determinants of the public’s behavioral response is crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread. While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response. The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors. Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors. It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship. These results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases. This information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.",2016 Oct 21,"['Moran, Kelly R.', 'Del Valle, Sara Y.']",PLoS One,,,False
1440ccd08199d80d52bb2e0e0431f020954709a5,PMC,A Meta-Analysis of the Association between Gender and Protective Behaviors in Response to Respiratory Epidemics and Pandemics,http://dx.doi.org/10.1371/journal.pone.0164541,PMC5074573,27768704,CC0,"Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society. The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread. Health-protective behaviors take several forms. Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport). Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions. Understanding the determinants of the public’s behavioral response is crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread. While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response. The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors. Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors. It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship. These results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases. This information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.",2016 Oct 21,"['Moran, Kelly R.', 'Del Valle, Sara Y.']",PLoS One,,,False
819d44a58a9c9fcd036cf7bfd4da0eda8f620bb3,PMC,A Meta-Analysis of the Association between Gender and Protective Behaviors in Response to Respiratory Epidemics and Pandemics,http://dx.doi.org/10.1371/journal.pone.0164541,PMC5074573,27768704,CC0,"Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society. The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread. Health-protective behaviors take several forms. Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport). Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions. Understanding the determinants of the public’s behavioral response is crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread. While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response. The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors. Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors. It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship. These results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases. This information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.",2016 Oct 21,"['Moran, Kelly R.', 'Del Valle, Sara Y.']",PLoS One,,,False
64b360d629a697bc95ae4dac99059fe91311a795,PMC,A Meta-Analysis of the Association between Gender and Protective Behaviors in Response to Respiratory Epidemics and Pandemics,http://dx.doi.org/10.1371/journal.pone.0164541,PMC5074573,27768704,CC0,"Respiratory infectious disease epidemics and pandemics are recurring events that levy a high cost on individuals and society. The health-protective behavioral response of the public plays an important role in limiting respiratory infectious disease spread. Health-protective behaviors take several forms. Behaviors can be categorized as pharmaceutical (e.g., vaccination uptake, antiviral use) or non-pharmaceutical (e.g., hand washing, face mask use, avoidance of public transport). Due to the limitations of pharmaceutical interventions during respiratory epidemics and pandemics, public health campaigns aimed at limiting disease spread often emphasize both non-pharmaceutical and pharmaceutical behavioral interventions. Understanding the determinants of the public’s behavioral response is crucial for devising public health campaigns, providing information to parametrize mathematical models, and ultimately limiting disease spread. While other reviews have qualitatively analyzed the body of work on demographic determinants of health-protective behavior, this meta-analysis quantitatively combines the results from 85 publications to determine the global relationship between gender and health-protective behavioral response. The results show that women in the general population are about 50% more likely than men to adopt/practice non-pharmaceutical behaviors. Conversely, men in the general population are marginally (about 12%) more likely than women to adopt/practice pharmaceutical behaviors. It is possible that factors other than pharmaceutical/non-pharmaceutical status not included in this analysis act as moderators of this relationship. These results suggest an inherent difference in how men and women respond to epidemic and pandemic respiratory infectious diseases. This information can be used to target specific groups when developing non-pharmaceutical public health campaigns and to parameterize epidemic models incorporating demographic information.",2016 Oct 21,"['Moran, Kelly R.', 'Del Valle, Sara Y.']",PLoS One,,,False
d51a55b2f7c2277e6435f0ecf13569863cc3adf3,PMC,Mechanisms of viral mutation,http://dx.doi.org/10.1007/s00018-016-2299-6,PMC5075021,27392606,CC BY,"The remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. Rates of spontaneous mutation vary amply among viruses. RNA viruses mutate faster than DNA viruses, single-stranded viruses mutate faster than double-strand virus, and genome size appears to correlate negatively with mutation rate. Viral mutation rates are modulated at different levels, including polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, and access to post-replicative repair. Additionally, massive numbers of mutations can be introduced by some virus-encoded diversity-generating elements, as well as by host-encoded cytidine/adenine deaminases. Our current knowledge of viral mutation rates indicates that viral genetic diversity is determined by multiple virus- and host-dependent processes, and that viral mutation rates can evolve in response to specific selective pressures.",2016 Jul 8,"['Sanjuán, Rafael', 'Domingo-Calap, Pilar']",Cell Mol Life Sci,,,True
5d445fbd8aa18aca2c2f7c947b25ddd62533f96b,PMC,"N-Desmethylclozapine, Fluoxetine, and Salmeterol Inhibit Postentry Stages of the Dengue Virus Life Cycle",http://dx.doi.org/10.1128/AAC.01367-16,PMC5075077,27572397,CC BY,"Around 10,000 people die each year due to severe dengue disease, and two-thirds of the world population lives in a region where dengue disease is endemic. There has been remarkable progress in dengue virus vaccine development; however, there are no licensed antivirals for dengue disease, and none appear to be in clinical trials. We took the approach of repositioning approved drugs for anti-dengue virus activity by screening a library of pharmacologically active compounds. We identified N-desmethylclozapine, fluoxetine hydrochloride, and salmeterol xinafoate as dengue virus inhibitors based on reductions in the numbers of infected cells and viral titers. Dengue virus RNA levels were diminished in inhibitor-treated cells, and this effect was specific to dengue virus, as other flaviviruses, such as Japanese encephalitis virus and West Nile virus, or other RNA viruses, such as respiratory syncytial virus and rotavirus, were not affected by these inhibitors. All three inhibitors specifically inhibited dengue virus replication with 50% inhibitory concentrations (IC(50)s) in the high-nanomolar range. Estimation of negative-strand RNA intermediates and time-of-addition experiments indicated that inhibition was occurring at a postentry stage, most probably at the initiation of viral RNA replication. Finally, we show that inhibition is most likely due to the modulation of the endolysosomal pathway and induction of autophagy.",2016 Oct 21,"['Medigeshi, Guruprasad R.', 'Kumar, Rinki', 'Dhamija, Ekta', 'Agrawal, Tanvi', 'Kar, Meenakshi']",Antimicrob Agents Chemother,,,True
4bf5ba8fe5af1bf36c9f2f3af74541fbda3a2c89,PMC,"N-Desmethylclozapine, Fluoxetine, and Salmeterol Inhibit Postentry Stages of the Dengue Virus Life Cycle",http://dx.doi.org/10.1128/AAC.01367-16,PMC5075077,27572397,CC BY,"Around 10,000 people die each year due to severe dengue disease, and two-thirds of the world population lives in a region where dengue disease is endemic. There has been remarkable progress in dengue virus vaccine development; however, there are no licensed antivirals for dengue disease, and none appear to be in clinical trials. We took the approach of repositioning approved drugs for anti-dengue virus activity by screening a library of pharmacologically active compounds. We identified N-desmethylclozapine, fluoxetine hydrochloride, and salmeterol xinafoate as dengue virus inhibitors based on reductions in the numbers of infected cells and viral titers. Dengue virus RNA levels were diminished in inhibitor-treated cells, and this effect was specific to dengue virus, as other flaviviruses, such as Japanese encephalitis virus and West Nile virus, or other RNA viruses, such as respiratory syncytial virus and rotavirus, were not affected by these inhibitors. All three inhibitors specifically inhibited dengue virus replication with 50% inhibitory concentrations (IC(50)s) in the high-nanomolar range. Estimation of negative-strand RNA intermediates and time-of-addition experiments indicated that inhibition was occurring at a postentry stage, most probably at the initiation of viral RNA replication. Finally, we show that inhibition is most likely due to the modulation of the endolysosomal pathway and induction of autophagy.",2016 Oct 21,"['Medigeshi, Guruprasad R.', 'Kumar, Rinki', 'Dhamija, Ekta', 'Agrawal, Tanvi', 'Kar, Meenakshi']",Antimicrob Agents Chemother,,,True
ab128bd5ddc658efa99c3c318f4ccf64c5eaea3b,PMC,Experimental Piscine orthoreovirus infection mediates protection against pancreas disease in Atlantic salmon (Salmo salar),http://dx.doi.org/10.1186/s13567-016-0389-y,PMC5075195,27769313,CC BY,"Viral diseases are among the main challenges in farming of Atlantic salmon (Salmo salar). The most prevalent viral diseases in Norwegian salmon aquaculture are heart and skeletal muscle inflammation (HSMI) caused by Piscine orthoreovirus (PRV), and pancreas disease (PD) caused by Salmonid alphavirus (SAV). Both PRV and SAV target heart and skeletal muscles, but SAV additionally targets exocrine pancreas. PRV and SAV are often present in the same locations and co-infections occur, but the effect of this crosstalk on disease development has not been investigated. In the present experiment, the effect of a primary PRV infection on subsequent SAV infection was studied. Atlantic salmon were infected with PRV by cohabitation, followed by addition of SAV shedder fish 4 or 10 weeks after the initial PRV infection. Histopathological evaluation, monitoring of viral RNA levels and host gene expression analysis were used to assess disease development. Significant reduction of SAV RNA levels and of PD specific histopathological changes were observed in the co-infected groups compared to fish infected by SAV only. A strong correlation was found between histopathological development and expression of disease related genes in heart. In conclusion, experimentally PRV infected salmon are less susceptible to secondary SAV infection and development of PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0389-y) contains supplementary material, which is available to authorized users.",2016 Oct 21,"['Lund, Morten', 'Røsæg, Magnus Vikan', 'Krasnov, Aleksei', 'Timmerhaus, Gerrit', 'Nyman, Ingvild Berg', 'Aspehaug, Vidar', 'Rimstad, Espen', 'Dahle, Maria Krudtaa']",Vet Res,,,False
97828b05cc598211ed632a6d931a13575c7181a6,PMC,Experimental Piscine orthoreovirus infection mediates protection against pancreas disease in Atlantic salmon (Salmo salar),http://dx.doi.org/10.1186/s13567-016-0389-y,PMC5075195,27769313,CC BY,"Viral diseases are among the main challenges in farming of Atlantic salmon (Salmo salar). The most prevalent viral diseases in Norwegian salmon aquaculture are heart and skeletal muscle inflammation (HSMI) caused by Piscine orthoreovirus (PRV), and pancreas disease (PD) caused by Salmonid alphavirus (SAV). Both PRV and SAV target heart and skeletal muscles, but SAV additionally targets exocrine pancreas. PRV and SAV are often present in the same locations and co-infections occur, but the effect of this crosstalk on disease development has not been investigated. In the present experiment, the effect of a primary PRV infection on subsequent SAV infection was studied. Atlantic salmon were infected with PRV by cohabitation, followed by addition of SAV shedder fish 4 or 10 weeks after the initial PRV infection. Histopathological evaluation, monitoring of viral RNA levels and host gene expression analysis were used to assess disease development. Significant reduction of SAV RNA levels and of PD specific histopathological changes were observed in the co-infected groups compared to fish infected by SAV only. A strong correlation was found between histopathological development and expression of disease related genes in heart. In conclusion, experimentally PRV infected salmon are less susceptible to secondary SAV infection and development of PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0389-y) contains supplementary material, which is available to authorized users.",2016 Oct 21,"['Lund, Morten', 'Røsæg, Magnus Vikan', 'Krasnov, Aleksei', 'Timmerhaus, Gerrit', 'Nyman, Ingvild Berg', 'Aspehaug, Vidar', 'Rimstad, Espen', 'Dahle, Maria Krudtaa']",Vet Res,,,False
5c322466f751d5543c600586f1df5db18a2ca2b9,PMC,Experimental Piscine orthoreovirus infection mediates protection against pancreas disease in Atlantic salmon (Salmo salar),http://dx.doi.org/10.1186/s13567-016-0389-y,PMC5075195,27769313,CC BY,"Viral diseases are among the main challenges in farming of Atlantic salmon (Salmo salar). The most prevalent viral diseases in Norwegian salmon aquaculture are heart and skeletal muscle inflammation (HSMI) caused by Piscine orthoreovirus (PRV), and pancreas disease (PD) caused by Salmonid alphavirus (SAV). Both PRV and SAV target heart and skeletal muscles, but SAV additionally targets exocrine pancreas. PRV and SAV are often present in the same locations and co-infections occur, but the effect of this crosstalk on disease development has not been investigated. In the present experiment, the effect of a primary PRV infection on subsequent SAV infection was studied. Atlantic salmon were infected with PRV by cohabitation, followed by addition of SAV shedder fish 4 or 10 weeks after the initial PRV infection. Histopathological evaluation, monitoring of viral RNA levels and host gene expression analysis were used to assess disease development. Significant reduction of SAV RNA levels and of PD specific histopathological changes were observed in the co-infected groups compared to fish infected by SAV only. A strong correlation was found between histopathological development and expression of disease related genes in heart. In conclusion, experimentally PRV infected salmon are less susceptible to secondary SAV infection and development of PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0389-y) contains supplementary material, which is available to authorized users.",2016 Oct 21,"['Lund, Morten', 'Røsæg, Magnus Vikan', 'Krasnov, Aleksei', 'Timmerhaus, Gerrit', 'Nyman, Ingvild Berg', 'Aspehaug, Vidar', 'Rimstad, Espen', 'Dahle, Maria Krudtaa']",Vet Res,,,False
84befea7ee1f85d2e9367d83bdb4834d56f9682a,PMC,Experimental Piscine orthoreovirus infection mediates protection against pancreas disease in Atlantic salmon (Salmo salar),http://dx.doi.org/10.1186/s13567-016-0389-y,PMC5075195,27769313,CC BY,"Viral diseases are among the main challenges in farming of Atlantic salmon (Salmo salar). The most prevalent viral diseases in Norwegian salmon aquaculture are heart and skeletal muscle inflammation (HSMI) caused by Piscine orthoreovirus (PRV), and pancreas disease (PD) caused by Salmonid alphavirus (SAV). Both PRV and SAV target heart and skeletal muscles, but SAV additionally targets exocrine pancreas. PRV and SAV are often present in the same locations and co-infections occur, but the effect of this crosstalk on disease development has not been investigated. In the present experiment, the effect of a primary PRV infection on subsequent SAV infection was studied. Atlantic salmon were infected with PRV by cohabitation, followed by addition of SAV shedder fish 4 or 10 weeks after the initial PRV infection. Histopathological evaluation, monitoring of viral RNA levels and host gene expression analysis were used to assess disease development. Significant reduction of SAV RNA levels and of PD specific histopathological changes were observed in the co-infected groups compared to fish infected by SAV only. A strong correlation was found between histopathological development and expression of disease related genes in heart. In conclusion, experimentally PRV infected salmon are less susceptible to secondary SAV infection and development of PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0389-y) contains supplementary material, which is available to authorized users.",2016 Oct 21,"['Lund, Morten', 'Røsæg, Magnus Vikan', 'Krasnov, Aleksei', 'Timmerhaus, Gerrit', 'Nyman, Ingvild Berg', 'Aspehaug, Vidar', 'Rimstad, Espen', 'Dahle, Maria Krudtaa']",Vet Res,,,True
f071dcbf396ad4171f3984d42f08291385ea9cf7,PMC,"Rapid Detection Strategies for the Global Threat of Zika Virus: Current State, New Hypotheses, and Limitations",http://dx.doi.org/10.3389/fmicb.2016.01685,PMC5075579,27822207,CC BY,"The current scenario regarding the widespread Zika virus (ZIKV) has resulted in numerous diagnostic studies, specifically in South America and in locations where there is frequent entry of travelers returning from ZIKV-affected areas, including pregnant women with or without clinical symptoms of ZIKV infection. The World Health Organization, WHO, announced that millions of cases of ZIKV are likely to occur in the USA in the near future. This situation has created an alarming public health emergency of international concern requiring the detection of this life-threatening viral candidate due to increased cases of newborn microcephaly associated with ZIKV infection. Hence, this review reports possible methods and strategies for the fast and reliable detection of ZIKV with particular emphasis on current updates, knowledge, and new hypotheses that might be helpful for medical professionals in poor and developing countries that urgently need to address this problem. In particular, we emphasize liposome-based biosensors. Although these biosensors are currently among the less popular tools for human disease detection, they have become useful tools for the screening and detection of pathogenic bacteria, fungi, and viruses because of their versatile advantageous features compared to other sensing devices. This review summarizes the currently available methods employed for the rapid detection of ZIKV and suggests an innovative approach involving the application of a liposome-based hypothesis for the development of new strategies for ZIKV detection and their use as effective biomedicinal tools.",2016 Oct 24,"['Shukla, Shruti', 'Hong, Sung-Yong', 'Chung, Soo Hyun', 'Kim, Myunghee']",Front Microbiol,,,True
891be4e9dc60d9b0c9ff79d35e11576ceeb8a592,PMC,Role of Antioxidants and Natural Products in Inflammation,http://dx.doi.org/10.1155/2016/5276130,PMC5075620,27803762,CC BY,"Inflammation is a comprehensive array of physiological response to a foreign organism, including human pathogens, dust particles, and viruses. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. Recent investigations have clarified that inflammation is a major factor for the progression of various chronic diseases/disorders, including diabetes, cancer, cardiovascular diseases, eye disorders, arthritis, obesity, autoimmune diseases, and inflammatory bowel disease. Free radical productions from different biological and environmental sources are due to an imbalance of natural antioxidants which further leads to various inflammatory associated diseases. In this review article, we have outlined the inflammatory process and its cellular mechanisms involved in the progression of various chronic modern human diseases. In addition, we have discussed the role of free radicals-induced tissue damage, antioxidant defence, and molecular mechanisms in chronic inflammatory diseases/disorders. The systematic knowledge regarding the role of inflammation and its associated adverse effects can provide a clear understanding in the development of innovative therapeutic targets from natural sources that are intended for suppression of various chronic inflammations associated diseases.",2016 Oct 10,"['Arulselvan, Palanisamy', 'Fard, Masoumeh Tangestani', 'Tan, Woan Sean', 'Gothai, Sivapragasam', 'Fakurazi, Sharida', 'Norhaizan, Mohd Esa', 'Kumar, S. Suresh']",Oxid Med Cell Longev,,,True
b3790b85395ee7e6d6abffce6fdee7ebe6090aac,PMC,"Respiratory microbes present in the nasopharynx of children hospitalised with suspected pulmonary tuberculosis in Cape Town, South Africa",http://dx.doi.org/10.1186/s12879-016-1934-z,PMC5075757,27776489,CC BY,"BACKGROUND: Lower respiratory tract infection in children is increasingly thought to be polymicrobial in origin. Children with symptoms suggestive of pulmonary tuberculosis (PTB) may have tuberculosis, other respiratory tract infections or co-infection with Mycobacterium tuberculosis and other pathogens. We aimed to identify the presence of potential respiratory pathogens in nasopharyngeal (NP) samples from children with suspected PTB. METHOD: NP samples collected from consecutive children presenting with suspected PTB at Red Cross Children’s Hospital (Cape Town, South Africa) were tested by multiplex real-time RT-PCR. Mycobacterial liquid culture and Xpert MTB/RIF was performed on 2 induced sputa obtained from each participant. Children were categorised as definite-TB (culture or qPCR [Xpert MTB/RIF] confirmed), unlikely-TB (improvement of symptoms without TB treatment on follow-up) and unconfirmed-TB (all other children). RESULTS: Amongst 214 children with a median age of 36 months (interquartile range, [IQR] 19–66 months), 34 (16 %) had definite-TB, 86 (40 %) had unconfirmed-TB and 94 (44 %) were classified as unlikely-TB. Moraxella catarrhalis (64 %), Streptococcus pneumoniae (42 %), Haemophilus influenzae spp (29 %) and Staphylococcus aureus (22 %) were the most common bacteria detected in NP samples. Other bacteria detected included Mycoplasma pneumoniae (9 %), Bordetella pertussis (7 %) and Chlamydophila pneumoniae (4 %). The most common viruses detected included metapneumovirus (19 %), rhinovirus (15 %), influenza virus C (9 %), adenovirus (7 %), cytomegalovirus (7 %) and coronavirus O43 (5.6 %). Both bacteria and viruses were detected in 73, 55 and 56 % of the definite, unconfirmed and unlikely-TB groups, respectively. There were no significant differences in the distribution of respiratory microbes between children with and without TB. Using quadratic discriminant analysis, human metapneumovirus, C. pneumoniae, coronavirus 043, influenza virus C virus, rhinovirus and cytomegalovirus best discriminated children with definite-TB from the other groups of children. CONCLUSIONS: A broad range of potential respiratory pathogens was detected in children with suspected TB. There was no clear association between TB categorisation and detection of a specific pathogen. Further work is needed to explore potential pathogen interactions and their role in the pathogenesis of PTB. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1934-z) contains supplementary material, which is available to authorized users.",2016 Oct 24,"['Dube, Felix S.', 'Kaba, Mamadou', 'Robberts, F. J. Lourens', 'Tow, Lemese Ah', 'Lubbe, Sugnet', 'Zar, Heather J.', 'Nicol, Mark P.']",BMC Infect Dis,,,False
4e3d9e4efadec3ac6b84928d59d18992b155d3ea,PMC,"Respiratory microbes present in the nasopharynx of children hospitalised with suspected pulmonary tuberculosis in Cape Town, South Africa",http://dx.doi.org/10.1186/s12879-016-1934-z,PMC5075757,27776489,CC BY,"BACKGROUND: Lower respiratory tract infection in children is increasingly thought to be polymicrobial in origin. Children with symptoms suggestive of pulmonary tuberculosis (PTB) may have tuberculosis, other respiratory tract infections or co-infection with Mycobacterium tuberculosis and other pathogens. We aimed to identify the presence of potential respiratory pathogens in nasopharyngeal (NP) samples from children with suspected PTB. METHOD: NP samples collected from consecutive children presenting with suspected PTB at Red Cross Children’s Hospital (Cape Town, South Africa) were tested by multiplex real-time RT-PCR. Mycobacterial liquid culture and Xpert MTB/RIF was performed on 2 induced sputa obtained from each participant. Children were categorised as definite-TB (culture or qPCR [Xpert MTB/RIF] confirmed), unlikely-TB (improvement of symptoms without TB treatment on follow-up) and unconfirmed-TB (all other children). RESULTS: Amongst 214 children with a median age of 36 months (interquartile range, [IQR] 19–66 months), 34 (16 %) had definite-TB, 86 (40 %) had unconfirmed-TB and 94 (44 %) were classified as unlikely-TB. Moraxella catarrhalis (64 %), Streptococcus pneumoniae (42 %), Haemophilus influenzae spp (29 %) and Staphylococcus aureus (22 %) were the most common bacteria detected in NP samples. Other bacteria detected included Mycoplasma pneumoniae (9 %), Bordetella pertussis (7 %) and Chlamydophila pneumoniae (4 %). The most common viruses detected included metapneumovirus (19 %), rhinovirus (15 %), influenza virus C (9 %), adenovirus (7 %), cytomegalovirus (7 %) and coronavirus O43 (5.6 %). Both bacteria and viruses were detected in 73, 55 and 56 % of the definite, unconfirmed and unlikely-TB groups, respectively. There were no significant differences in the distribution of respiratory microbes between children with and without TB. Using quadratic discriminant analysis, human metapneumovirus, C. pneumoniae, coronavirus 043, influenza virus C virus, rhinovirus and cytomegalovirus best discriminated children with definite-TB from the other groups of children. CONCLUSIONS: A broad range of potential respiratory pathogens was detected in children with suspected TB. There was no clear association between TB categorisation and detection of a specific pathogen. Further work is needed to explore potential pathogen interactions and their role in the pathogenesis of PTB. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1934-z) contains supplementary material, which is available to authorized users.",2016 Oct 24,"['Dube, Felix S.', 'Kaba, Mamadou', 'Robberts, F. J. Lourens', 'Tow, Lemese Ah', 'Lubbe, Sugnet', 'Zar, Heather J.', 'Nicol, Mark P.']",BMC Infect Dis,,,True
e26b6173b72a118e2b65869e3ba0cc176a3bb751,PMC,Comparison of incubation period distribution of human infections with MERS-CoV in South Korea and Saudi Arabia,http://dx.doi.org/10.1038/srep35839,PMC5075793,27775012,CC BY,"The incubation period is an important epidemiologic distribution, it is often incorporated in case definitions, used to determine appropriate quarantine periods, and is an input to mathematical modeling studies. Middle East Respiratory Syndrome coronavirus (MERS) is an emerging infectious disease in the Arabian Peninsula. There was a large outbreak of MERS in South Korea in 2015. We examined the incubation period distribution of MERS coronavirus infection for cases in South Korea and in Saudi Arabia. Using parametric and nonparametric methods, we estimated a mean incubation period of 6.9 days (95% credibility interval: 6.3–7.5) for cases in South Korea and 5.0 days (95% credibility interval: 4.0–6.6) among cases in Saudi Arabia. In a log-linear regression model, the mean incubation period was 1.42 times longer (95% credibility interval: 1.18–1.71) among cases in South Korea compared to Saudi Arabia. The variation that we identified in the incubation period distribution between locations could be associated with differences in ascertainment or reporting of exposure dates and illness onset dates, differences in the source or mode of infection, or environmental differences.",2016 Oct 24,"['Virlogeux, Victor', 'Fang, Vicky J.', 'Park, Minah', 'Wu, Joseph T.', 'Cowling, Benjamin J.']",Sci Rep,,,True
0fc01f8a6bb755f52b6407df7cb8c9accd15450e,PMC,Involvement of P2X7 receptor signaling on regulating the differentiation of Th17 cells and type II collagen-induced arthritis in mice,http://dx.doi.org/10.1038/srep35804,PMC5075966,27775097,CC BY,"Interleukin (IL)-17 producing T helper (Th17) cells are major effector cells in the pathogenesis of rheumatoid arthritis (RA). The P2X7 receptor (P2X7R) has emerged as a potential site in the regulation of inflammation in RA but little is known of its functional role on the differentiation of Th17 cells. This study investigates the in vitro and in vivo effects of P2X7R on Th17 cell differentiation during type II collagen (CII) induced experimental arthritis model. In CII-treated dendritic cells (DCs) and DC/CD4(+) T coculture system, pretreatment with pharmacological antagonists of P2X7R (Suramin and A-438079) caused strong inhibition of production of Th17-promoting cytokines (IL-1β, TGF-β1, IL-23p19 and IL-6). Exposure to CII induced the elevation of mRNAs encoding retinoic acid receptor-related orphan receptor α and γt, which were abolished by pretreatment with P2X7R antagonists. Furthermore, blocking P2X7R signaling abolished the CII-mediated increase in IL-17A. Blockade of P2X7R remarkably inhibited hind paw swelling and ameliorated pathological changes in ankle joint of the collagen-induced arthritis mice. Thus, we demonstrated a novel function for P2X7R signaling in regulating CII-induced differentiation of Th17 cells. P2X7R signaling facilitates the development of the sophisticated network of DC-derived cytokines that favors a Th17 phenotype.",2016 Oct 24,"['Fan, Zhi-Dan', 'Zhang, Ya-Yuan', 'Guo, Yi-Hong', 'Huang, Na', 'Ma, Hui-Hui', 'Huang, Hui', 'Yu, Hai-Guo']",Sci Rep,,,True
c7d87ef17e8863714b7ccd091373777918e9131d,PMC,The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study,http://dx.doi.org/10.1186/s13613-016-0203-z,PMC5078123,27778310,CC BY,"BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) has caused several hospital outbreaks, including a major outbreak at King Abdulaziz Medical City, a 940-bed tertiary-care hospital in Riyadh, Saudi Arabia (August–September 2015). To learn from our experience, we described the critical care response to the outbreak. METHODS: This observational study was conducted at the Intensive Care Department which covered 5 ICUs with 60 single-bedded rooms. We described qualitatively and, as applicable, quantitatively the response of intensive care services to the outbreak. The clinical course and outcomes of healthcare workers (HCWs) who had MERS were noted. RESULTS: Sixty-three MERS patients were admitted to 3 MERS-designated ICUs during the outbreak (peak census = 27 patients on August 25, 2015, and the last new case on September 13, 2015). Most patients had multiorgan failure. Eight HCWs had MERS requiring ICU admission (median stay = 28 days): Seven developed acute respiratory distress syndrome, four were treated with prone positioning, four needed continuous renal replacement therapy and one had extracorporeal membrane oxygenation. The hospital mortality of ICU MERS patients was 63.4 % (0 % for the HCWs). In response to the outbreak, the number of negative-pressure rooms was increased from 14 to 38 rooms in 3 MERS-designated ICUs. Patients were managed with a nurse-to-patient ratio of 1:0.8. Infection prevention practices were intensified. As a surrogate, surface disinfectant and hand hygiene gel consumption increased by ~30 % and 17 N95 masks were used per patient/day on average. Family visits were restricted to 2 h/day. Although most ICU staff expressed concerns about acquiring MERS, all reported to work normally. During the outbreak, 27.0 % of nurses and 18.4 % of physicians working in the MERS-designated ICUs reported upper respiratory symptoms, and were tested for MERS-CoV. Only 2/196 (1.0 %) ICU nurses and 1/80 (1.3 %) physician tested positive, had mild disease and recovered fully. The total sick leave duration was 138 days for nurses and 30 days for physicians. CONCLUSIONS: Our hospital outbreak of MERS resulted in 63 patients requiring organ support and prolonged ICU stay with a high mortality rate. The ICU response required careful facility and staff management and proper infection control and prevention practices.",2016 Oct 24,"['Al-Dorzi, Hasan M.', 'Aldawood, Abdulaziz S.', 'Khan, Raymond', 'Baharoon, Salim', 'Alchin, John D.', 'Matroud, Amal A.', 'Al Johany, Sameera M.', 'Balkhy, Hanan H.', 'Arabi, Yaseen M.']",Ann Intensive Care,,,True
01bf19ea2cb2baab425377eaae3286190e9bf975,PMC,Endogenous Retrovirus ev21 Dose Not Recombine with ALV-J and Induces the Expression of ISGs in the Host,http://dx.doi.org/10.3389/fcimb.2016.00140,PMC5078265,27826543,CC BY,"Avian leukosis virus subgroup J (ALV-J) infection can cause tumors and immunosuppression. Endogenous viruses integrate into host genomes and can recombine with exogenous avian leukosis virus (ALV). In this study, we analyzed the interaction of endogenous retrovirus 21 (ev21) with the ALV-J in late-feathering Chinese yellow chicken. Two ALV-J strains M180 and K243 were isolated from late-feathering and fast-feathering Chinese yellow chicken flocks, respectively. The env gene of the two strains showed 94.2–94.8% nucleotide identity with reference ALV-J strains. Compared with the env gene and the LTR of ev21 and M180, the nucleotide identity of LTR was 69.7% and env gene was 58.4%, respectively, especially the amino acid identity of env gene as low as 14.2%. Phylogenetic analysis of the nucleotide sequence of the env gene and the 3′LTR showed that M180 was closely related to ALV-J, and was located in a distinct group with ev21 in the phylogenetic tree. Using co-immunoprecipitation (co-IP), we next demonstrate that the envelope protein of ev21 does not interact with the M180 envelope protein. We further show that the envelope protein of ev21 cannot activate ALV-J LTR promoter activity using luciferase-reporter assays. qPCR and western blot analysis revealed that envelope protein of endogenous ev21 can facilitate the expression of PKR at 6h post ALV-J infection (hpi) and facilitate the expression of ISG12 and CH25H at 24 hpi. However, the expression of the env gene of M180 strain was not significantly at 6 and 24 hpi. We conclude that there is no evidence of recombination between endogenous retrovirus ev21 and ALV-J strain M180 in late-feathering Chinese yellow chicken, and envelope protein of ev21 can affect the expression of host ISGs, but appears not to influence the replication of ALV-J strain M180. This is the first report of interaction among the endogenous retrovirus ev21, ALV-J and the late-feathering chicken.",2016 Oct 25,"['Feng, Min', 'Tan, Yan', 'Dai, Manman', 'Li, Yuanfang', 'Xie, Tingting', 'Li, Hongmei', 'Shi, Meiqing', 'Zhang, Xiquan']",Front Cell Infect Microbiol,,,True
ac8d2e900ee0c6d713d153782a530ddee6d606aa,PMC,Influenza A virus PB1-F2 protein prolongs viral shedding in chickens lengthening the transmission window,http://dx.doi.org/10.1099/jgv.0.000584,PMC5078828,27558742,CC BY,"Avian influenza is a significant economic burden on the poultry industry in geographical regions where it is enzootic. It also poses a public health concern when avian influenza subtypes infect humans, often with high mortality. Understanding viral genetic factors which positively contribute to influenza A virus (IAV) fitness – infectivity, spread and pathogenesis – is of great importance both for human and livestock health. PB1-F2 is a small accessory protein encoded by IAV and in mammalian hosts has been implicated in a wide range of functions that contribute to increased pathogenesis. In the avian host, the protein has been understudied despite high-level full-length conservation in avian IAV isolates, which is in contrast to the truncations of the PB1-F2 length frequently found in mammalian host isolates. Here we report that the presence of a full-length PB1-F2 protein, from a low pathogenicity H9N2 avian influenza virus, prolongs infectious virus shedding from directly inoculated chickens, thereby enhancing transmission of the virus by lengthening the transmission window to contact birds. As well as extending transmission, the presence of a full-length PB1-F2 suppresses pathogenicity evidenced by an increased minimum lethal dose in embryonated chicken eggs and increasing survival in directly infected birds when compared to a virus lacking an ORF for PB1-F2. We propose that there is a positive pressure to maintain a full-length functional PB1-F2 protein upon infection of avian hosts as it contributes to the effective transmission of IAV in the field.",2016 Oct 13,"['James, Joe', 'Howard, Wendy', 'Iqbal, Munir', 'Nair, Venugopal K.', 'Barclay, Wendy S.', 'Shelton, Holly']",J Gen Virol,,,True
6bde48b237b5f69005bfa28740e4cbeb056ecd46,PMC,Influenza A virus PB1-F2 protein prolongs viral shedding in chickens lengthening the transmission window,http://dx.doi.org/10.1099/jgv.0.000584,PMC5078828,27558742,CC BY,"Avian influenza is a significant economic burden on the poultry industry in geographical regions where it is enzootic. It also poses a public health concern when avian influenza subtypes infect humans, often with high mortality. Understanding viral genetic factors which positively contribute to influenza A virus (IAV) fitness – infectivity, spread and pathogenesis – is of great importance both for human and livestock health. PB1-F2 is a small accessory protein encoded by IAV and in mammalian hosts has been implicated in a wide range of functions that contribute to increased pathogenesis. In the avian host, the protein has been understudied despite high-level full-length conservation in avian IAV isolates, which is in contrast to the truncations of the PB1-F2 length frequently found in mammalian host isolates. Here we report that the presence of a full-length PB1-F2 protein, from a low pathogenicity H9N2 avian influenza virus, prolongs infectious virus shedding from directly inoculated chickens, thereby enhancing transmission of the virus by lengthening the transmission window to contact birds. As well as extending transmission, the presence of a full-length PB1-F2 suppresses pathogenicity evidenced by an increased minimum lethal dose in embryonated chicken eggs and increasing survival in directly infected birds when compared to a virus lacking an ORF for PB1-F2. We propose that there is a positive pressure to maintain a full-length functional PB1-F2 protein upon infection of avian hosts as it contributes to the effective transmission of IAV in the field.",2016 Oct 13,"['James, Joe', 'Howard, Wendy', 'Iqbal, Munir', 'Nair, Venugopal K.', 'Barclay, Wendy S.', 'Shelton, Holly']",J Gen Virol,,,False
af5f5cae93582ca713bbc2abaea17d7898b63f72,PMC,Pathogenesis of Korean Sapelovirus A in piglets and chicks,http://dx.doi.org/10.1099/jgv.0.000571,PMC5078829,27487773,CC BY,"Sapelovirus A (SV-A), formerly known as porcine sapelovirus as a member of a new genus Sapelovirus, is known to cause enteritis, pneumonia, polioencephalomyelitis and reproductive disorders in pigs. We have recently identified α2,3-linked sialic acid on GD1a ganglioside as a functional SV-A receptor rich in the cells of pigs and chickens. However, the role of GD1a in viral pathogenesis remains elusive. Here, we demonstrated that a Korean SV-A strain could induce diarrhoea and intestinal pathology in piglets but not in chicks. Moreover, this Korean SV-A strain had mild extra-intestinal tropisms appearing as mild, non-suppurative myelitis, encephalitis and pneumonia in piglets, but not in chicks. By real-time reverse transcription (RT) PCR, higher viral RNA levels were detected in faecal samples than in sera or extra-intestinal organs from virus-inoculated piglets. Immunohistochemistry confirmed that high viral antigens were detected in the epithelial cells of intestines from virus-inoculated piglets but not from chicks. This Korean SV-A strain could bind the cultured cell lines originated from various species, but replication occurred only in cells of porcine origin. These data indicated that this Korean SV-A strain could replicate and induce pathology in piglets but not in chicks, suggesting that additional porcine-specific factors are required for virus entry and replication. In addition, this Korean SV-A strain is enteropathogenic, but could spread to the bloodstream from the gut and disseminate to extra-intestinal organs and tissues. These results will contribute to our understanding of SV-A pathogenesis so that efficient anti-sapelovirus drugs and vaccines could be developed in the future.",2016 Oct 13,"['Kim, Deok-Song', 'Kang, Mun-Il', 'Son, Kyu-Yeol', 'Bak, Geon-Yong', 'Park, Jun-Gyu', 'Hosmillo, Myra', 'Seo, Ja-Young', 'Kim, Ji-Yun', 'Alfajaro, Mia Madel', 'Soliman, Mahmoud', 'Baek, Yeong-Bin', 'Cho, Eun-Hyo', 'Lee, Ju-Hwan', 'Kwon, Joseph', 'Choi, Jong-Soon', 'Goodfellow, Ian', 'Cho, Kyoung-Oh']",J Gen Virol,,,True
96a89e5c0df1a32d5e2864966057fab04d2e3a23,PMC,Fast type I interferon response protects astrocytes from flavivirus infection and virus-induced cytopathic effects,http://dx.doi.org/10.1186/s12974-016-0748-7,PMC5078952,27776548,CC BY,"BACKGROUND: Neurotropic flaviviruses such as tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV), West Nile virus (WNV), and Zika virus (ZIKV) are causative agents of severe brain-related diseases including meningitis, encephalitis, and microcephaly. We have previously shown that local type I interferon response within the central nervous system (CNS) is involved in the protection of mice against tick-borne flavivirus infection. However, the cells responsible for mounting this protective response are not defined. METHODS: Primary astrocytes were isolated from wild-type (WT) and interferon alpha receptor knock out (IFNAR(−/−)) mice and infected with neurotropic flaviviruses. Viral replication and spread, IFN induction and response, and cellular viability were analyzed. Transcriptional levels in primary astrocytes treated with interferon or supernatant from virus-infected cells were analyzed by RNA sequencing and evaluated by different bioinformatics tools. RESULTS: Here, we show that astrocytes control viral replication of different TBEV strains, JEV, WNV, and ZIKV. In contrast to fibroblast, astrocytes mount a rapid interferon response and restrict viral spread. Furthermore, basal expression levels of key interferon-stimulated genes are high in astrocytes compared to mouse embryonic fibroblasts. Bioinformatic analysis of RNA-sequencing data reveals that astrocytes have established a basal antiviral state which contributes to the rapid viral recognition and upregulation of interferons. The most highly upregulated pathways in neighboring cells were linked to type I interferon response and innate immunity. The restriction in viral growth was dependent on interferon signaling, since loss of the interferon receptor, or its blockade in wild-type cells, resulted in high viral replication and virus-induced cytopathic effects. Astrocyte supernatant from TBEV-infected cells can restrict TBEV growth in astrocytes already 6 h post infection, the effect on neurons is highly reinforced, and astrocyte supernatant from 3 h post infection is already protective. CONCLUSIONS: These findings suggest that the combination of an intrinsic constitutive antiviral response and the fast induction of type I IFN production by astrocytes play an important role in self-protection of astrocytes and suppression of flavivirus replication in the CNS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-016-0748-7) contains supplementary material, which is available to authorized users.",2016 Oct 24,"['Lindqvist, Richard', 'Mundt, Filip', 'Gilthorpe, Jonathan D.', 'Wölfel, Silke', 'Gekara, Nelson O.', 'Kröger, Andrea', 'Överby, Anna K.']",J Neuroinflammation,,,True
44cbdded77107e8c97330deef77b1b761a9bb229,PMC,Differential expression of lncRNAs during the HIV replication cycle: an underestimated layer in the HIV-host interplay,http://dx.doi.org/10.1038/srep36111,PMC5080576,27782208,CC BY,"Studying the effects of HIV infection on the host transcriptome has typically focused on protein-coding genes. However, recent advances in the field of RNA sequencing revealed that long non-coding RNAs (lncRNAs) add an extensive additional layer to the cell’s molecular network. Here, we performed transcriptome profiling throughout a primary HIV infection in vitro to investigate lncRNA expression at the different HIV replication cycle processes (reverse transcription, integration and particle production). Subsequently, guilt-by-association, transcription factor and co-expression analysis were performed to infer biological roles for the lncRNAs identified in the HIV-host interplay. Many lncRNAs were suggested to play a role in mechanisms relying on proteasomal and ubiquitination pathways, apoptosis, DNA damage responses and cell cycle regulation. Through transcription factor binding analysis, we found that lncRNAs display a distinct transcriptional regulation profile as compared to protein coding mRNAs, suggesting that mRNAs and lncRNAs are independently modulated. In addition, we identified five differentially expressed lncRNA-mRNA pairs with mRNA involvement in HIV pathogenesis with possible cis regulatory lncRNAs that control nearby mRNA expression and function. Altogether, the present study demonstrates that lncRNAs add a new dimension to the HIV-host interplay and should be further investigated as they may represent targets for controlling HIV replication.",2016 Oct 26,"['Trypsteen, Wim', 'Mohammadi, Pejman', 'Van Hecke, Clarissa', 'Mestdagh, Pieter', 'Lefever, Steve', 'Saeys, Yvan', 'De Bleser, Pieter', 'Vandesompele, Jo', 'Ciuffi, Angela', 'Vandekerckhove, Linos', 'De Spiegelaere, Ward']",Sci Rep,,,True
9f13bcae6ae451b9a0c4d2f22c6557fcfbc2c3f7,PMC,Differential expression of lncRNAs during the HIV replication cycle: an underestimated layer in the HIV-host interplay,http://dx.doi.org/10.1038/srep36111,PMC5080576,27782208,CC BY,"Studying the effects of HIV infection on the host transcriptome has typically focused on protein-coding genes. However, recent advances in the field of RNA sequencing revealed that long non-coding RNAs (lncRNAs) add an extensive additional layer to the cell’s molecular network. Here, we performed transcriptome profiling throughout a primary HIV infection in vitro to investigate lncRNA expression at the different HIV replication cycle processes (reverse transcription, integration and particle production). Subsequently, guilt-by-association, transcription factor and co-expression analysis were performed to infer biological roles for the lncRNAs identified in the HIV-host interplay. Many lncRNAs were suggested to play a role in mechanisms relying on proteasomal and ubiquitination pathways, apoptosis, DNA damage responses and cell cycle regulation. Through transcription factor binding analysis, we found that lncRNAs display a distinct transcriptional regulation profile as compared to protein coding mRNAs, suggesting that mRNAs and lncRNAs are independently modulated. In addition, we identified five differentially expressed lncRNA-mRNA pairs with mRNA involvement in HIV pathogenesis with possible cis regulatory lncRNAs that control nearby mRNA expression and function. Altogether, the present study demonstrates that lncRNAs add a new dimension to the HIV-host interplay and should be further investigated as they may represent targets for controlling HIV replication.",2016 Oct 26,"['Trypsteen, Wim', 'Mohammadi, Pejman', 'Van Hecke, Clarissa', 'Mestdagh, Pieter', 'Lefever, Steve', 'Saeys, Yvan', 'De Bleser, Pieter', 'Vandesompele, Jo', 'Ciuffi, Angela', 'Vandekerckhove, Linos', 'De Spiegelaere, Ward']",Sci Rep,,,True
d259c80b55cb69486ef75e66d13fe60688a1e028,PMC,Middle East Respiratory Coronavirus Accessory Protein 4a Inhibits PKR-Mediated Antiviral Stress Responses,http://dx.doi.org/10.1371/journal.ppat.1005982,PMC5081173,27783669,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infections that can be life-threatening. To establish an infection and spread, MERS-CoV, like most other viruses, must navigate through an intricate network of antiviral host responses. Besides the well-known type I interferon (IFN-α/β) response, the protein kinase R (PKR)-mediated stress response is being recognized as an important innate response pathway. Upon detecting viral dsRNA, PKR phosphorylates eIF2α, leading to the inhibition of cellular and viral translation and the formation of stress granules (SGs), which are increasingly recognized as platforms for antiviral signaling pathways. It is unknown whether cellular infection by MERS-CoV activates the stress response pathway or whether the virus has evolved strategies to suppress this infection-limiting pathway. Here, we show that cellular infection with MERS-CoV does not lead to the formation of SGs. By transiently expressing the MERS-CoV accessory proteins individually, we identified a role of protein 4a (p4a) in preventing activation of the stress response pathway. Expression of MERS-CoV p4a impeded dsRNA-mediated PKR activation, thereby rescuing translation inhibition and preventing SG formation. In contrast, p4a failed to suppress stress response pathway activation that is independent of PKR and dsRNA. MERS-CoV p4a is a dsRNA binding protein. Mutation of the dsRNA binding motif in p4a disrupted its PKR antagonistic activity. By inserting p4a in a picornavirus lacking its natural PKR antagonist, we showed that p4a exerts PKR antagonistic activity also under infection conditions. However, a recombinant MERS-CoV deficient in p4a expression still suppressed SG formation, indicating the expression of at least one other stress response antagonist. This virus also suppressed the dsRNA-independent stress response pathway. Thus, MERS-CoV interferes with antiviral stress responses using at least two different mechanisms, with p4a suppressing the PKR-dependent stress response pathway, probably by sequestering dsRNA. MERS-CoV p4a represents the first coronavirus stress response antagonist described.",2016 Oct 26,"['Rabouw, Huib H.', 'Langereis, Martijn A.', 'Knaap, Robert C. M.', 'Dalebout, Tim J.', 'Canton, Javier', 'Sola, Isabel', 'Enjuanes, Luis', 'Bredenbeek, Peter J.', 'Kikkert, Marjolein', 'de Groot, Raoul J.', 'van Kuppeveld, Frank J. M.']",PLoS Pathog,,,True
ec99df59b1b63a5da4b31c203e8e1eab566fba68,PMC,Mechanism of Fibronectin Binding to Human Trabecular Meshwork Exosomes and Its Modulation by Dexamethasone,http://dx.doi.org/10.1371/journal.pone.0165326,PMC5081181,27783649,CC BY,"Exosomes are emerging as important mediators of cell-matrix interactions by means of specific adhesion proteins. Changes in the tissue-specific exosomal protein expression may underlie pathological conditions whereby extracellular matrix turnover and homeostasis is disrupted. Ocular hypertension due to extracellular matrix accumulation in the trabecular meshwork is a hallmark of glucocorticoid-induced glaucoma. In the trabecular meshwork, exosomal fibronectin mediates cell matrix interactions at cellular structures called “invadosomes”. Trabecular meshwork cells use invadosomes to turn over their surrounding matrix and maintain passageways for flow of aqueous humor. In this study, we observed that human trabecular meshwork explants treated with dexamethasone released exosomes with significantly reduced amounts of fibronectin bound per exosome. Further, we found that exosome-fibronectin binding is heparan sulfate-dependent, consistent with our observation that trabecular meshwork exosomes are enriched in the heparin/heparan sulfate binding annexins A2 and A6. In this way, dexamethasone-treated explants released exosomes with a significant reduction in annexin A2 and A6 per exosome. Interestingly, we did not detect exosomal matrix metalloproteinases, but we identified abundant dipeptidyl peptidase 4, a serine protease whose activity was reduced on exosomes isolated from dexamethasone-treated explants. Together, our findings demonstrate mechanistically how corticosteroid-induced alterations in exosomal adhesion cargo and properties can account for the pathological matrix accumulation seen in many glaucoma patients.",2016 Oct 26,"['Dismuke, W. Michael', 'Klingeborn, Mikael', 'Stamer, W. Daniel']",PLoS One,,,True
45510604115249ca0df4da68553498f079b7911f,PMC,Building Viral Replication Organelles: Close Encounters of the Membrane Types,http://dx.doi.org/10.1371/journal.ppat.1005912,PMC5082816,27788266,CC BY,,2016 Oct 27,"['Nagy, Peter D.', 'Strating, Jeroen R. P. M.', 'van Kuppeveld, Frank J. M.']",PLoS Pathog,,,True
eddeda2da89b486d01f0afaf67af974b9f214306,PMC,A Generic Quantitative Risk Assessment Framework for the Entry of Bat-Borne Zoonotic Viruses into the European Union,http://dx.doi.org/10.1371/journal.pone.0165383,PMC5082878,27788234,CC BY,"Bat-borne viruses have been linked to a number of zoonotic diseases; in 2014 there have been human cases of Nipah virus (NiV) in Bangladesh and Ebola virus in West and Central Africa. Here we describe a model designed to provide initial quantitative predictions of the risk of entry of such viruses to European Union (EU) Member States (MSs) through four routes: human travel, legal trade (e.g. fruit and animal products), live animal movements and illegal importation of bushmeat. The model utilises available datasets to assess the movement via these routes between individual countries of the world and EU MSs. These data are combined with virus specific data to assess the relative risk of entry between EU MSs. As a case study, the model was parameterised for NiV. Scenario analyses showed that the selection of exporting countries with NiV and potentially contaminated trade products were essential to the accuracy of all model outputs. Uncertainty analyses of other model parameters identified that the model expected number of years to an introduction event within the EU was highly susceptible to the prevalence of NiV in bats. The relative rankings of the MSs and routes, however, were more robust. The UK, the Netherlands and Germany were consistently the most likely points of entry and the ranking of most MSs varied by no more than three places (maximum variation five places). Legal trade was consistently the most likely route of entry, only falling below human travel when the estimate of the prevalence of NiV in bats was particularly low. Any model-based calculation is dependent on the data available to feed into the model and there are distinct gaps in our knowledge, particularly in regard to various pathogen/virus as well as host/bat characteristics. However, the strengths of this model lie in the provision of relative comparisons of risk among routes and MSs. The potential for expansion of the model to include other routes and viruses and the possibility of rapid parameterisation demonstrates its potential for use in an outbreak situation.",2016 Oct 27,"['Simons, Robin R. L.', 'Horigan, Verity', 'Gale, Paul', 'Kosmider, Rowena D.', 'Breed, Andrew C.', 'Snary, Emma L.']",PLoS One,,,True
a382a62bbd387279327333abd96be2aa76445ace,PMC,Microorganisms Causing Community-Acquired Acute Bronchitis: The Role of Bacterial Infection,http://dx.doi.org/10.1371/journal.pone.0165553,PMC5082923,27788254,CC BY,"BACKGROUND: Although acute bronchitis is quite common, there is relatively limited information regarding the microorganisms that are involved in this illness. METHODS: We performed a prospective study of acute bronchitis at 31 hospitals and clinics in Korea from July 2011 to June 2012. Sputum specimens were collected for polymerase chain reaction (PCR) and culture of microorganisms. RESULTS: Of the 811 enrolled patients, 291 had acceptable sputum specimens that were included for analysis of the etiologic distribution. With multiplex PCR testing, viruses were identified in 36.1% (105/291), most commonly rhinovirus (25.8%) and coronavirus (3.8%). Typical bacteria were isolated in 126/291 (43.3%) patients. Among these patients Haemophilus influenzae (n = 39) and Streptococcus pneumoniae (n = 30) were isolated most commonly; atypical bacteria were identified in 44 (15.1%) patients. Bacteria-only, virus-only, and mixed infections (bacteria plus virus) accounted for 36.7% (98/291), 17.2% (50/291), and 18.9% (55/291) of infections, respectively. In particular, 52.4% of patients with viral infection had a concurrent bacterial infection, and rhinovirus was the most common virus in mixed infections (40/55). Additionally, infections with typical bacteria were more common in patients with chronic lung disease (p = 0.029), and typical bacterial infections showed a trend towards a higher prevalence with older age (p = 0.001). CONCLUSIONS: Bacteria were associated with almost half of community-acquired acute bronchitis cases. Additional studies are required to further illuminate the role of bacteria and to identify patient groups most likely to benefit from antibiotic treatment.",2016 Oct 27,"['Park, Ji Young', 'Park, Sunghoon', 'Lee, Sun Hwa', 'Lee, Myung Goo', 'Park, Yong Bum', 'Oh, Kil Chan', 'Lee, Jae-Myung', 'Kim, Do Il', 'Seo, Ki-Hyun', 'Shin, Kyeong-Cheol', 'Yoo, Kwang Ha', 'Ko, Yongchun', 'Jang, Seung Hun', 'Jung, Ki-Suck', 'Hwang, Yong Il']",PLoS One,,,True
0892e16c218542d3a099d7b10aec24cab4bfce55,PMC,Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model,http://dx.doi.org/10.18632/oncotarget.9114,PMC5085160,27145284,CC BY,"Advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. The local antibody delivery led to marked immune checkpoint blockade. Tumor growth diminished 5 times and tumor weight reduced 50–80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo. These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen.",2016 Apr 29,"['Suarez, Eloah Rabello', 'Chang, De-Kuan', 'Sun, Jiusong', 'Sui, Jianhua', 'Freeman, Gordon J.', 'Signoretti, Sabina', 'Zhu, Quan', 'Marasco, Wayne A.']",Oncotarget,,,True
74eccf041d34a1cebad39e386cba617d1bd996ea,PMC,Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model,http://dx.doi.org/10.18632/oncotarget.9114,PMC5085160,27145284,CC BY,"Advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. The local antibody delivery led to marked immune checkpoint blockade. Tumor growth diminished 5 times and tumor weight reduced 50–80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo. These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen.",2016 Apr 29,"['Suarez, Eloah Rabello', 'Chang, De-Kuan', 'Sun, Jiusong', 'Sui, Jianhua', 'Freeman, Gordon J.', 'Signoretti, Sabina', 'Zhu, Quan', 'Marasco, Wayne A.']",Oncotarget,,,False
0660d9281c1607ca1ca9cb62dfa00b56f49ddee1,PMC,The Last Ten Years of Advancements in Plant-Derived Recombinant Vaccines against Hepatitis B,http://dx.doi.org/10.3390/ijms17101715,PMC5085746,27754367,CC BY,"Disease prevention through vaccination is considered to be the greatest contribution to public health over the past century. Every year more than 100 million children are vaccinated with the standard World Health Organization (WHO)-recommended vaccines including hepatitis B (HepB). HepB is the most serious type of liver infection caused by the hepatitis B virus (HBV), however, it can be prevented by currently available recombinant vaccine, which has an excellent record of safety and effectiveness. To date, recombinant vaccines are produced in many systems of bacteria, yeast, insect, and mammalian and plant cells. Among these platforms, the use of plant cells has received considerable attention in terms of intrinsic safety, scalability, and appropriate modification of target proteins. Research groups worldwide have attempted to develop more efficacious plant-derived vaccines for over 30 diseases, most frequently HepB and influenza. More inspiring, approximately 12 plant-made antigens have already been tested in clinical trials, with successful outcomes. In this study, the latest information from the last 10 years on plant-derived antigens, especially hepatitis B surface antigen, approaches are reviewed and breakthroughs regarding the weak points are also discussed.",2016 Oct 13,"['Joung, Young Hee', 'Park, Se Hee', 'Moon, Ki-Beom', 'Jeon, Jae-Heung', 'Cho, Hye-Sun', 'Kim, Hyun-Soon']",Int J Mol Sci,,,True
1db51d8c217cae965ebad4dabf0651a2ecd62e53,PMC,Viral Metagenomics on Blood-Feeding Arthropods as a Tool for Human Disease Surveillance,http://dx.doi.org/10.3390/ijms17101743,PMC5085771,27775568,CC BY,"Surveillance and monitoring of viral pathogens circulating in humans and wildlife, together with the identification of emerging infectious diseases (EIDs), are critical for the prediction of future disease outbreaks and epidemics at an early stage. It is advisable to sample a broad range of vertebrates and invertebrates at different temporospatial levels on a regular basis to detect possible candidate viruses at their natural source. However, virus surveillance systems can be expensive, costly in terms of finances and resources and inadequate for sampling sufficient numbers of different host species over space and time. Recent publications have presented the concept of a new virus surveillance system, coining the terms “flying biological syringes”, “xenosurveillance” and “vector-enabled metagenomics”. According to these novel and promising surveillance approaches, viral metagenomics on engorged mosquitoes might reflect the viral diversity of numerous mammals, birds and humans, combined in the mosquitoes’ blood meal during feeding on the host. In this review article, we summarize the literature on vector-enabled metagenomics (VEM) techniques and its application in disease surveillance in humans. Furthermore, we highlight the combination of VEM and “invertebrate-derived DNA” (iDNA) analysis to identify the host DNA within the mosquito midgut.",2016 Oct 19,"['Brinkmann, Annika', 'Nitsche, Andreas', 'Kohl, Claudia']",Int J Mol Sci,,,True
fba08f3ce8a1335d06623126e44863cf1e73a509,PMC,Mutagenic Effects of Ribavirin on Hepatitis E Virus—Viral Extinction versus Selection of Fitness-Enhancing Mutations,http://dx.doi.org/10.3390/v8100283,PMC5086615,27754363,CC BY,"Hepatitis E virus (HEV), an important agent of viral hepatitis worldwide, can cause severe courses of infection in pregnant women and immunosuppressed patients. To date, HEV infections can only be treated with ribavirin (RBV). Major drawbacks of this therapy are that RBV is not approved for administration to pregnant women and that the virus can acquire mutations, which render the intra-host population less sensitive or even resistant to RBV. One of the proposed modes of action of RBV is a direct mutagenic effect on viral genomes, inducing mismatches and subsequent nucleotide substitutions. These transition events can drive the already error-prone viral replication beyond an error threshold, causing viral population extinction. In contrast, the expanded heterogeneous viral population can facilitate selection of mutant viruses with enhanced replication fitness. Emergence of these mutant viruses can lead to therapeutic failure. Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis.",2016 Oct 13,"['Todt, Daniel', 'Walter, Stephanie', 'Brown, Richard J. P.', 'Steinmann, Eike']",Viruses,,,True
39683dd78bcf6b301cbed610b6e3213a5ce33380,PMC,Griffithsin: An Antiviral Lectin with Outstanding Therapeutic Potential,http://dx.doi.org/10.3390/v8100296,PMC5086628,27783038,CC BY,"Griffithsin (GRFT), an algae-derived lectin, is one of the most potent viral entry inhibitors discovered to date. It is currently being developed as a microbicide with broad-spectrum activity against several enveloped viruses. GRFT can inhibit human immunodeficiency virus (HIV) infection at picomolar concentrations, surpassing the ability of most anti-HIV agents. The potential to inhibit other viruses as well as parasites has also been demonstrated. Griffithsin’s antiviral activity stems from its ability to bind terminal mannoses present in high-mannose oligosaccharides and crosslink these glycans on the surface of the viral envelope glycoproteins. Here, we review structural and biochemical studies that established mode of action and facilitated construction of GRFT analogs, mechanisms that may lead to resistance, and in vitro and pre-clinical results that support the therapeutic potential of this lectin.",2016 Oct 24,"['Lusvarghi, Sabrina', 'Bewley, Carole A.']",Viruses,,,True
9db44eda8b352d1e7e5f73d7b5587659aa256151,PMC,The Influenza Virus Protein PB1-F2 Increases Viral Pathogenesis through Neutrophil Recruitment and NK Cells Inhibition,http://dx.doi.org/10.1371/journal.pone.0165361,PMC5087861,27798704,CC BY,"The influenza A virus (IAV) PB1-F2 protein is a virulence factor contributing to the pathogenesis observed during IAV infections in mammals. In this study, using a mouse model, we compared the host response associated with PB1-F2 with an early transcriptomic signature that was previously associated with neutrophils and consecutively fatal IAV infections. This allowed us to show that PB1-F2 is partly involved in neutrophil-related mechanisms leading to death. Using neutropenic mice, we confirmed that the harmful effect of PB1-F2 is due to an excessive inflammation mediated by an increased neutrophil mobilization. We identified the downstream effects of this PB1-F2-exacerbated neutrophil recruitment. PB1-F2 had no impact on the lymphocyte recruitment in the airways at day 8 pi. However, functional genomics analysis and flow cytometry in broncho-alveolar lavages at 4 days pi revealed that PB1-F2 induced a NK cells deficiency. Thus, our results identify PB1-F2 as an important immune disruptive factor during the IAV infection.",2016 Oct 31,"['Vidy, Aurore', 'Maisonnasse, Pauline', 'Da Costa, Bruno', 'Delmas, Bernard', 'Chevalier, Christophe', 'Le Goffic, Ronan']",PLoS One,,,True
028949943b9f67a541a4d59504d87b9ddbe7713b,PMC,The Influenza Virus Protein PB1-F2 Increases Viral Pathogenesis through Neutrophil Recruitment and NK Cells Inhibition,http://dx.doi.org/10.1371/journal.pone.0165361,PMC5087861,27798704,CC BY,"The influenza A virus (IAV) PB1-F2 protein is a virulence factor contributing to the pathogenesis observed during IAV infections in mammals. In this study, using a mouse model, we compared the host response associated with PB1-F2 with an early transcriptomic signature that was previously associated with neutrophils and consecutively fatal IAV infections. This allowed us to show that PB1-F2 is partly involved in neutrophil-related mechanisms leading to death. Using neutropenic mice, we confirmed that the harmful effect of PB1-F2 is due to an excessive inflammation mediated by an increased neutrophil mobilization. We identified the downstream effects of this PB1-F2-exacerbated neutrophil recruitment. PB1-F2 had no impact on the lymphocyte recruitment in the airways at day 8 pi. However, functional genomics analysis and flow cytometry in broncho-alveolar lavages at 4 days pi revealed that PB1-F2 induced a NK cells deficiency. Thus, our results identify PB1-F2 as an important immune disruptive factor during the IAV infection.",2016 Oct 31,"['Vidy, Aurore', 'Maisonnasse, Pauline', 'Da Costa, Bruno', 'Delmas, Bernard', 'Chevalier, Christophe', 'Le Goffic, Ronan']",PLoS One,,,False
8745be1dc78adeffdc2f243e3597390ddd07b456,PMC,A retrospective study detects a novel variant of porcine epidemic diarrhea virus in England in archived material from the year 2000,http://dx.doi.org/10.7717/peerj.2564,PMC5088618,27812401,CC BY,"Outbreaks of porcine epidemic diarrhea (PED) were first recorded in England in the 1970s and continued to be confirmed until 2002. Retrospective analysis of archived material from one of the last confirmed cases in England in the year 2000 demonstrates the previous existence of a very diverse PED virus strain. Following the outbreaks of PED in North America in 2013, there has been renewed interest in phylogenetic analysis of sequences from PEDV strains worldwide. There is a gap in the available sequence data between the mid 1980s and the mid 2000s. This work is an example of how this gap can be at least partially filled by the examination of archived material.",2016 Oct 27,"['Steinbach, Falko', 'Dastjerdi, Akbar', 'Peake, Julie', 'La Rocca, S. Anna', 'Tobin, Frank P.', 'Frossard, Jean-Pierre', 'Williamson, Susanna']",PeerJ,,,True
711a2350fec569de818a1bd51ab4a3a8b793918c,PMC,"Key Ethical Issues Discussed at CDC-Sponsored International, Regional Meetings to Explore Cultural Perspectives and Contexts on Pandemic Influenza Preparedness and Response",http://dx.doi.org/10.15171/ijhpm.2016.55,PMC5088725,27801360,CC BY,"Background: Recognizing the importance of having a broad exploration of how cultural perspectives may shape thinking about ethical considerations, the Centers for Disease Control and Prevention (CDC) funded four regional meetings in Africa, Asia, Latin America, and the Eastern Mediterranean to explore these perspectives relevant to pandemic influenza preparedness and response. The meetings were attended by 168 health professionals, scientists, academics, ethicists, religious leaders, and other community members representing 40 countries in these regions. Methods: We reviewed the meeting reports, notes and stories and mapped outcomes to the key ethical challenges for pandemic influenza response described in the World Health Organization’s (WHO’s) guidance, Ethical Considerations in Developing a Public Health Response to Pandemic Influenza: transparency and public engagement, allocation of resources, social distancing, obligations to and of healthcare workers, and international collaboration. Results: The important role of transparency and public engagement were widely accepted among participants. However, there was general agreement that no ""one size fits all"" approach to allocating resources can address the variety of economic, cultural and other contextual factors that must be taken into account. The importance of social distancing as a tool to limit disease transmission was also recognized, but the difficulties associated with this measure were acknowledged. There was agreement that healthcare workers often have competing obligations and that government has a responsibility to assist healthcare workers in doing their job by providing appropriate training and equipment. Finally, there was agreement about the importance of international collaboration for combating global health threats. Conclusion: Although some cultural differences in the values that frame pandemic preparedness and response efforts were observed, participants generally agreed on the key ethical principles discussed in the WHO’s guidance. Most significantly the input gathered from these regional meetings pointed to the important role that procedural ethics can play in bringing people and countries together to respond to the shared health threat posed by a pandemic influenza despite the existence of cultural differences.",2016 May 17,"['Lor, Aun', 'Thomas, James C.', 'Barrett, Drue H.', 'Ortmann, Leonard W.', 'Herrera Guibert, Dionisio J.']",Int J Health Policy Manag,,,True
a3f9d6933e737f7f0a7bd27a54a9bb4882eca041,PMC,Clinical and Epidemiologic Characteristics of Hospitalized Patients with Laboratory-Confirmed Respiratory Syncytial Virus Infection in Eastern China between 2009 and 2013: A Retrospective Study,http://dx.doi.org/10.1371/journal.pone.0165437,PMC5089734,27802292,CC BY,"Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality worldwide in children aged <5 years and older adults with acute lower respiratory infections (ALRIs). However, few studies regarding the epidemiology of hospitalizations for RSV infection have been performed previously in China. Here, we aimed to describe the clinical and epidemiologic characteristics of hospitalized patients with laboratory-confirmed RSV infection in eastern China. Active surveillance for hospitalized ALRI patients using a broad case definition based on symptoms was performed from 2009–2013 in 12 sentinel hospitals in eastern China. Clinical and epidemiologic data pertaining to hospitalized patients of all ages with laboratory-confirmed RSV infection by PCR assay were collected and analyzed in this study. From 2009 to 2013, 1046 hospitalized patients with laboratory-confirmed RSV infection were enrolled in this study, and 14.7% of patients had subtype A, 24.2% of patients had subtype B, 23.8% of patients with subtype not performed, and 37.3% of patients had RSV coinfections with other viruses. RSV and influenza coinfections (33.3%) were the most common coinfections noted in this study. Moreover, young children aged <5 years (89.1%, 932/1046), particularly young infants aged <1 year (43.3%, 453/1046), represented the highest proportion of patients with RSV infections. In contrast, older adults aged ≥60 years (1.1%, 12/1046) represented the lowest proportion of patients with RSV infections among enrolled patients. The peak RSV infection period occurred mainly during autumn and winter, and 57% and 66% of patients exhibited symptoms such as fever (body temperature ≥38°C) and cough separately. Additionally, only a small number of patients were treated with broad-spectrum antiviral drugs, and most of patients were treated with antimicrobial drugs that were not appropriate for RSV infection. RSV is a leading viral pathogen and a common cause of viral infection in young children aged <5 years with ALRIs in eastern China. Effective vaccines and antiviral agents targeting RSV are needed to mitigate its large public health impact.",2016 Nov 1,"['Cui, Dawei', 'Feng, Luzhao', 'Chen, Yu', 'Lai, Shengjie', 'Zhang, Zike', 'Yu, Fei', 'Zheng, Shufa', 'Li, Zhongjie', 'Yu, Hongjie']",PLoS One,,,True
9586f483c1144f2e1b3105d587b826f467d02832,PMC,Autographa californica Multiple Nucleopolyhedrovirus Ac34 Protein Retains Cellular Actin-Related Protein 2/3 Complex in the Nucleus by Subversion of CRM1-Dependent Nuclear Export,http://dx.doi.org/10.1371/journal.ppat.1005994,PMC5089780,27802336,CC BY,"Actin, nucleation-promoting factors (NPFs), and the actin-related protein 2/3 complex (Arp2/3) are key elements of the cellular actin polymerization machinery. With nuclear actin polymerization implicated in ever-expanding biological processes and the discovery of the nuclear import mechanisms of actin and NPFs, determining Arp2/3 nucleo-cytoplasmic shuttling mechanism is important for understanding the function of nuclear actin. A unique feature of alphabaculovirus infection of insect cells is the robust nuclear accumulation of Arp2/3, which induces actin polymerization in the nucleus to assist in virus replication. We found that Ac34, a viral late gene product encoded by the alphabaculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV), is involved in Arp2/3 nuclear accumulation during virus infection. Further assays revealed that the subcellular distribution of Arp2/3 under steady-state conditions is controlled by chromosomal maintenance 1 (CRM1)-dependent nuclear export. Upon AcMNPV infection, Ac34 inhibits CRM1 pathway and leads to Arp2/3 retention in the nucleus.",2016 Nov 1,"['Mu, Jingfang', 'Zhang, Yongli', 'Hu, Yangyang', 'Hu, Xue', 'Zhou, Yuan', 'Zhao, He', 'Pei, Rongjuan', 'Wu, Chunchen', 'Chen, Jizheng', 'Zhao, Han', 'Yang, Kai', 'van Oers, Monique M.', 'Chen, Xinwen', 'Wang, Yun']",PLoS Pathog,,,True
126b264339dd9d8ee65cc747822e16c83af57e12,PMC,Sustaining Interferon Induction by a High-Passage Atypical Porcine Reproductive and Respiratory Syndrome Virus Strain,http://dx.doi.org/10.1038/srep36312,PMC5090871,27805024,CC BY,"Porcine reproductive and respiratory syndrome virus (PRRSV) strain A2MC2 induces type I interferons in cultured cells. The objective of this study was to attenuate this strain by serial passaging in MARC-145 cells and assess its virulence and immunogenicity in pigs. The A2MC2 serially passaged 90 times (A2MC2-P90) retains the feature of interferon induction. The A2MC2-P90 replicates faster with a higher virus yield than wild type A2MC2 virus. Infection of primary pulmonary alveolar macrophages (PAMs) also induces interferons. Sequence analysis showed that the A2MC2-P90 has genomic nucleic acid identity of 99.8% to the wild type but has a deletion of 543 nucleotides in nsp2. The deletion occurred in passage 60. The A2MC2-P90 genome has a total of 35 nucleotide variations from the wild type, leading to 26 amino acid differences. Inoculation of three-week-old piglets showed that A2MC2-P90 is avirulent and elicits immune response. Compared with Ingelvac PRRS(®) MLV strain, A2MC2-P90 elicits higher virus neutralizing antibodies. The attenuated IFN-inducing A2MC2-P90 should be useful for development of an improved PRRSV vaccine.",2016 Nov 2,"['Ma, Zexu', 'Yu, Ying', 'Xiao, Yueqiang', 'Opriessnig, Tanja', 'Wang, Rong', 'Yang, Liping', 'Nan, Yuchen', 'Samal, Siba K.', 'Halbur, Patrick G.', 'Zhang, Yan-Jin']",Sci Rep,,,True
67ad221f50d67a02b89b0ea67da2a74d6d463d16,PMC,Directional and reoccurring sequence change in zoonotic RNA virus genomes visualized by time-series word count,http://dx.doi.org/10.1038/srep36197,PMC5093548,27808119,CC BY,"Ebolavirus, MERS coronavirus and influenza virus are zoonotic RNA viruses, which mutate very rapidly. Viral growth depends on many host factors, but human cells may not provide the ideal growth conditions for viruses invading from nonhuman hosts. The present time-series analyses of short and long oligonucleotide compositions in these genomes showed directional changes in their composition after invasion from a nonhuman host, which are thought to recur after future invasions. In the recent West Africa Ebola outbreak, directional time-series changes in a wide range of oligonucleotides were observed in common for three geographic areas, and the directional changes were observed also for the recent MERS coronavirus epidemics starting in the Middle East. In addition, common directional changes in human influenza A viruses were observed for three subtypes, whose epidemics started independently. Long oligonucleotides that showed an evident directional change observed in common for the three subtypes corresponded to some of influenza A siRNAs, whose activities have been experimentally proven. Predicting directional and reoccurring changes in oligonucleotide composition should become important for designing diagnostic RT-PCR primers and therapeutic oligonucleotides with long effectiveness.",2016 Nov 3,"['Wada, Yoshiko', 'Wada, Kennosuke', 'Iwasaki, Yuki', 'Kanaya, Shigehiko', 'Ikemura, Toshimichi']",Sci Rep,,,True
e07f0ed517b0561a441652c8f5deaad4e80aafc5,PMC,Directional and reoccurring sequence change in zoonotic RNA virus genomes visualized by time-series word count,http://dx.doi.org/10.1038/srep36197,PMC5093548,27808119,CC BY,"Ebolavirus, MERS coronavirus and influenza virus are zoonotic RNA viruses, which mutate very rapidly. Viral growth depends on many host factors, but human cells may not provide the ideal growth conditions for viruses invading from nonhuman hosts. The present time-series analyses of short and long oligonucleotide compositions in these genomes showed directional changes in their composition after invasion from a nonhuman host, which are thought to recur after future invasions. In the recent West Africa Ebola outbreak, directional time-series changes in a wide range of oligonucleotides were observed in common for three geographic areas, and the directional changes were observed also for the recent MERS coronavirus epidemics starting in the Middle East. In addition, common directional changes in human influenza A viruses were observed for three subtypes, whose epidemics started independently. Long oligonucleotides that showed an evident directional change observed in common for the three subtypes corresponded to some of influenza A siRNAs, whose activities have been experimentally proven. Predicting directional and reoccurring changes in oligonucleotide composition should become important for designing diagnostic RT-PCR primers and therapeutic oligonucleotides with long effectiveness.",2016 Nov 3,"['Wada, Yoshiko', 'Wada, Kennosuke', 'Iwasaki, Yuki', 'Kanaya, Shigehiko', 'Ikemura, Toshimichi']",Sci Rep,,,False
033e16498132db048e7fbf0a64d99694bd302a7b,PMC,"Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone",http://dx.doi.org/10.1186/s40249-016-0195-9,PMC5094140,27806732,CC BY,"BACKGROUND: Clinical and laboratory data were collected and analysed from patients with Ebola virus disease (EVD) in Jui Government Hospital in Freetown, Sierra Leone, where patients with EVD were received and/or treated from October 1, 2014 to March 21, 2015 during the West Africa EVD outbreak. METHODS: The study admitted 285 patients with confirmed EVD and followed them up till the endpoint (recovery or death). EVD was confirmed by quantitative RT-PCR assays detecting blood Ebola virus (EBOV). RESULTS: Among the 285 lab-confirmed EVD cases in Jui Government Hospital, 146 recovered and 139 died, with an overall survival rate of 51.23 %. Patients under the age of 6 years had a lower survival rate (37.50 %). Most non-survivors (79.86 %) died within 7 days after admission and the mean hospitalization time for non-survivors was 5.56 ± 6.11 days. More than half survivors (63.69 %) turned blood EBOV negative within 3 weeks after admission and the mean hospitalization time for survivors was 20.38 ± 7.58 days. High blood viral load (≥10(6) copies/ml) was found to be predictive of the non-survival outcome as indicated by the Receiver Operating Characteristic (ROC) curve analysis. The probability of patients’ survival was less than 15 % when blood viral load was greater than 10(6) copies/ml. Multivariate analyses showed that blood viral load (P = 0.005), confusion (P = 0.010), abdominal pain (P = 0.003), conjunctivitis (P = 0.035), and vomiting (P = 0.004) were factors independently associated with the outcomes of EVD patients. CONCLUSIONS: Most death occurred within 1 week after admission, and patients at the age of 6 or younger had a lower survival rate. Most surviving patients turned blood EBOV negative within 1–4 weeks after admission. Factors such as high blood viral load, confusion, abdominal pain, vomiting and conjunctivitis were associated with poor prognosis for EVD patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0195-9) contains supplementary material, which is available to authorized users.",2016 Nov 3,"['Ji, Ying-Jie', 'Duan, Xue-Zhang', 'Gao, Xu-Dong', 'Li, Lei', 'Li, Chen', 'Ji, Dong', 'Li, Wen-Gang', 'Wang, Li-Fu', 'Meng, Yu-Hua', 'Yang, Xiao', 'Ling, Bin-Fang', 'Song, Xue-Ai', 'Gu, Mei-Lei', 'Jiang, Tao', 'Koroma, She-Ku M.', 'Bangalie, James', 'Duan, Hui-Juan']",Infect Dis Poverty,,,False
4fd6ce6a0e0f551a80d019b4c9b6c25279605d91,PMC,"Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone",http://dx.doi.org/10.1186/s40249-016-0195-9,PMC5094140,27806732,CC BY,"BACKGROUND: Clinical and laboratory data were collected and analysed from patients with Ebola virus disease (EVD) in Jui Government Hospital in Freetown, Sierra Leone, where patients with EVD were received and/or treated from October 1, 2014 to March 21, 2015 during the West Africa EVD outbreak. METHODS: The study admitted 285 patients with confirmed EVD and followed them up till the endpoint (recovery or death). EVD was confirmed by quantitative RT-PCR assays detecting blood Ebola virus (EBOV). RESULTS: Among the 285 lab-confirmed EVD cases in Jui Government Hospital, 146 recovered and 139 died, with an overall survival rate of 51.23 %. Patients under the age of 6 years had a lower survival rate (37.50 %). Most non-survivors (79.86 %) died within 7 days after admission and the mean hospitalization time for non-survivors was 5.56 ± 6.11 days. More than half survivors (63.69 %) turned blood EBOV negative within 3 weeks after admission and the mean hospitalization time for survivors was 20.38 ± 7.58 days. High blood viral load (≥10(6) copies/ml) was found to be predictive of the non-survival outcome as indicated by the Receiver Operating Characteristic (ROC) curve analysis. The probability of patients’ survival was less than 15 % when blood viral load was greater than 10(6) copies/ml. Multivariate analyses showed that blood viral load (P = 0.005), confusion (P = 0.010), abdominal pain (P = 0.003), conjunctivitis (P = 0.035), and vomiting (P = 0.004) were factors independently associated with the outcomes of EVD patients. CONCLUSIONS: Most death occurred within 1 week after admission, and patients at the age of 6 or younger had a lower survival rate. Most surviving patients turned blood EBOV negative within 1–4 weeks after admission. Factors such as high blood viral load, confusion, abdominal pain, vomiting and conjunctivitis were associated with poor prognosis for EVD patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0195-9) contains supplementary material, which is available to authorized users.",2016 Nov 3,"['Ji, Ying-Jie', 'Duan, Xue-Zhang', 'Gao, Xu-Dong', 'Li, Lei', 'Li, Chen', 'Ji, Dong', 'Li, Wen-Gang', 'Wang, Li-Fu', 'Meng, Yu-Hua', 'Yang, Xiao', 'Ling, Bin-Fang', 'Song, Xue-Ai', 'Gu, Mei-Lei', 'Jiang, Tao', 'Koroma, She-Ku M.', 'Bangalie, James', 'Duan, Hui-Juan']",Infect Dis Poverty,,,True
202f004261b2489f0e28acebc96cba9ebb576860,PMC,Recombinase polymerase amplification assay for rapid detection of lumpy skin disease virus,http://dx.doi.org/10.1186/s12917-016-0875-5,PMC5094145,27806722,CC BY,"BACKGROUND: Lumpy skin disease virus (LSDV) is a Capripoxvirus infecting cattle and Buffalos. Lumpy skin disease (LSD) leads to significant economic losses due to hide damage, reduction of milk production, mastitis, infertility and mortalities (10 %). Early detection of the virus is crucial to start appropriate outbreak control measures. Veterinarians rely on the presence of the characteristic clinical signs of LSD. Laboratory diagnostics including virus isolation, sequencing and real-time polymerase chain reaction (PCR) are performed at well-equipped laboratories. In this study, a portable, simple, and rapid recombinase polymerase amplification (RPA) assay for the detection of LSDV-genome for the use on farms was developed. RESULTS: The LSDV RPA assay was performed at 42 °C and detected down to 179 DNA copies/reaction in a maximum of 15 min. Unspecific amplification was observed with neither LSDV-negative samples (n = 12) nor nucleic acid preparations from orf virus, bovine papular stomatitis virus, cowpoxvirus, Peste des petits ruminants and Blue tongue virus (serotypes 1, 6 and 8). The clinical sensitivity of the LSDV RPA assay matched 100 % (n = 22) to real-time PCR results. In addition, the LSDV RPA assay detected sheep and goat poxviruses. CONCLUSION: The LSDV RPA assay is a rapid and sensitive test that could be implemented in field or at quarantine stations for the identification of LSDV infected case. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0875-5) contains supplementary material, which is available to authorized users.",2016 Nov 2,"['Shalaby, Mohamed A.', 'El-Deeb, Ayman', 'El-Tholoth, Mohamed', 'Hoffmann, Donata', 'Czerny, Claus-Peter', 'Hufert, Frank T.', 'Weidmann, Manfred', 'Abd El Wahed, Ahmed']",BMC Vet Res,,,True
befd47f9dd7e050dcd46f483ca8e7bd902f4707f,PMC,A Comparative Study of Clinical Presentation and Risk Factors for Adverse Outcome in Patients Hospitalised with Acute Respiratory Disease Due to MERS Coronavirus or Other Causes,http://dx.doi.org/10.1371/journal.pone.0165978,PMC5094725,27812197,CC BY,"Middle East Respiratory syndrome (MERS) first emerged in Saudi Arabia in 2012 and remains a global health concern. The objective of this study was to compare the clinical features and risk factors for adverse outcome in patients with RT-PCR confirmed MERS and in those with acute respiratory disease who were MERS-CoV negative, presenting to the King Fahad Medical City (KFMC) in Riyadh between October 2012 and May 2014. The demographics, clinical and laboratory characteristics and clinical outcomes of patients with RT-PCR confirmed MERS-CoV infection was compared with those testing negative MERS-CoV PCR. Health care workers (HCW) with MERS were compared with MERS patients who were not health care workers. One hundred and fifty nine patients were eligible for inclusion. Forty eight tested positive for MERS CoV, 44 (92%) being hospital acquired infections and 23 were HCW. There were 111 MERS-CoV negative patients with acute respiratory illnesses included in this study as “negative controls”. Patient with confirmed MERS-CoV infection were not clinically distinguishable from those with negative MERS-CoV RT-PCR results although diarrhoea was commoner in MERS patients. A high level of suspicion in initiating laboratory tests for MERS-CoV is therefore indicated. Variables associated with adverse outcome were older age and diabetes as a co-morbid illness. Interestingly, co-morbid illnesses other than diabetes were not significantly associated with poor outcome. Health care workers with MERS had a markedly better clinical outcome compared to non HCW MERS patients.",2016 Nov 3,"['Garbati, Musa A.', 'Fagbo, Shamsudeen F.', 'Fang, Vicky J.', 'Skakni, Leila', 'Joseph, Mercy', 'Wani, Tariq A.', 'Cowling, Benjamin J.', 'Peiris, Malik', 'Hakawi, Ahmed']",PLoS One,,,True
605669a3876e7ff3961f0cca4c58a7059144d0ba,PMC,Waiting time to infectious disease emergence,http://dx.doi.org/10.1098/rsif.2016.0540,PMC5095216,27798277,CC BY,"Emerging diseases must make a transition from stuttering chains of transmission to sustained chains of transmission, but this critical transition need not coincide with the system becoming supercritical. That is, the introduction of infection to a supercritical system results in a significant fraction of the population becoming infected only with a certain probability. Understanding the waiting time to the first major outbreak of an emerging disease is then more complicated than determining when the system becomes supercritical. We treat emergence as a dynamic bifurcation, and use the concept of bifurcation delay to understand the time to emergence after a system becomes supercritical. Specifically, we consider an SIR model with a time-varying transmission term and random infections originating from outside the population. We derive an analytic density function for the delay times and find it to be, in general, in agreement with stochastic simulations. We find the key parameters to be the rate of introduction of infection and the rate of change of the basic reproductive ratio. These findings aid our understanding of real emergence events, and can be incorporated into early-warning systems aimed at forecasting disease risk.",2016 Oct,"['Dibble, Christopher J.', ""O'Dea, Eamon B."", 'Park, Andrew W.', 'Drake, John M.']",J R Soc Interface,,,True
5f96f9d0f4775e4803ec0d9c0b3c181a40ea27ce,PMC,Waiting time to infectious disease emergence,http://dx.doi.org/10.1098/rsif.2016.0540,PMC5095216,27798277,CC BY,"Emerging diseases must make a transition from stuttering chains of transmission to sustained chains of transmission, but this critical transition need not coincide with the system becoming supercritical. That is, the introduction of infection to a supercritical system results in a significant fraction of the population becoming infected only with a certain probability. Understanding the waiting time to the first major outbreak of an emerging disease is then more complicated than determining when the system becomes supercritical. We treat emergence as a dynamic bifurcation, and use the concept of bifurcation delay to understand the time to emergence after a system becomes supercritical. Specifically, we consider an SIR model with a time-varying transmission term and random infections originating from outside the population. We derive an analytic density function for the delay times and find it to be, in general, in agreement with stochastic simulations. We find the key parameters to be the rate of introduction of infection and the rate of change of the basic reproductive ratio. These findings aid our understanding of real emergence events, and can be incorporated into early-warning systems aimed at forecasting disease risk.",2016 Oct,"['Dibble, Christopher J.', ""O'Dea, Eamon B."", 'Park, Andrew W.', 'Drake, John M.']",J R Soc Interface,,,True
1621345a6fa32695580f1455de8a7f6284a0f9e9,PMC,Association of Mannose-binding Lectin Polymorphisms with Tuberculosis Susceptibility among Chinese,http://dx.doi.org/10.1038/srep36488,PMC5095599,27812036,CC BY,"Tuberculosis (TB) is caused by infection of Mycobacterium tuberculosis. Host genetic variability is an important determinant of the risk of developing TB in humans. Although the association between MBL2 polymorphisms and TB has been studied in various populations, the results are controversial. In this study four functional single-nucleotide polymorphisms (SNPs, H/L, X/Y, P/Q and A/B) across the MBL2 gene were genotyped by direct DNA sequencing of PCR products in a case-control population of Chinese Han origin, consisting of 1,020 patients with pulmonary TB and 1,020 controls. We found that individuals carrying variant allele at A/B (namely BB or AB genotypes) was associated with increased susceptibility to TB (odds ratios [OR] = 1.57, 95% confidence interval [CI] 1.30–1.91, P = 1.3 × 10(−6)). Additionally, LYPB haplotype showed a significant association with increased risk of TB (OR = 1.54, 95% CI 1.27–1.87, P = 4.2 × 10(−6); global haplotype association P = 3.5 × 10(−5)). Furthermore, individuals bearing low- or medium- MBL expression haplotype pairs had an increased risk of TB (OR = 1.56, 95% CI 1.29–1.90, P = 1.4 × 10(−6)). Thus, the reduced expression of functional MBL secondary to having MBL2 variants may partially mediate the increased susceptibility to TB risk.",2016 Nov 4,"['Liu, Cheng', 'He, Tao', 'Rong, Yanxiao', 'Du, Fengjiao', 'Ma, Dongxing', 'Wei, Yujie', 'Mei, Zhiqin', 'Wang, Yuling', 'Wang, Haibin', 'Zhu, Yuehua', 'Zhang, Zongde', 'Zheng, Li', 'Wu, Xueqiong', 'Liu, Huiliang', 'Ding, Wenjun']",Sci Rep,,,True
e1cb86642107f15ec6d854bebf9c8341d1416ef4,PMC,Strand-Exchange Nucleic Acid Circuitry with Enhanced Thermo-and Structure- Buffering Abilities Turns Gene Diagnostics Ultra-Reliable and Environmental Compatible,http://dx.doi.org/10.1038/srep36605,PMC5095676,27812041,CC BY,"Catalytic hairpin assembly (CHA) is one of the most promising nucleic acid amplification circuits based on toehold-mediated strand exchange reactions. But its performance is usually ruined by fluctuated environmental temperatures or unexpected self-structures existing in most real-world targets. Here we present an amide-assistant mechanism that successfully reduces the prevalence of these problems for CHA and maximizes its thermo- and structure- buffering abilities. Such an organic amide-promoted CHA (shortened as OHT-CHA) can unprecedentedly amplify through 4 °C to 60 °C without rebuilding sequences or concerning target complexity. We are then for the first time able to employ it as a direct and universal signal booster for loop mediated isothermal reaction (LAMP). LAMP is one of the most promising point-of-care (POC) gene amplifiers, but has been hard to detect precisely due to structured products and haunted off-target amplicons. OHT-CHA guarantees a significant and reliable signal for LAMP reaction amplified from as little as 10(−19) M virus gene. And one single set of OHT-CHA is qualified to any detection requirement, either in real-time at LAMP running temperature (~60 °C), or at end-point on a POC photon counter only holding environmental temperatures fluctuating between 4 °C to 42 °C.",2016 Nov 4,"['Zhu, Zhentong', 'Tang, Yidan', 'Jiang, Yu Sherry', 'Bhadra, Sanchita', 'Du, Yan', 'Ellington, Andrew D.', 'Li, Bingling']",Sci Rep,,,True
8a0b13901e64c9c2b9c0449cdcd7411ae0f1eac4,PMC,Anvillea garcinii extract inhibits the oxidative burst of primary human neutrophils,http://dx.doi.org/10.1186/s12906-016-1411-7,PMC5095960,27809835,CC BY,"BACKGROUND: Anvillea garcinii Coss. & Durieu (Anv) plant is used as a traditional North African medicine against several diseases associated with inflammation. At inflammatory sites, reactive oxygen species (ROS) produced in excess by activated phagocyte NADPH oxidase (NOX2) can accentuate inflammatory responses. Thus, we investigated if Anv-water soluble polysaccharides could modulate primary human neutrophil oxidative burst in vitro. METHODS: Human neutrophils were isolated from fresh whole blood and O(2) (.-) generation was measured by cytochrome c reduction assays. Western blots were used to analyse the translocation of PKC, p47(phox) (a key component of NOX2 activity) to neutrophil plasma membrane. Also, myeloperoxidase (MPO) release in the extracellular medium was studied by western blots. Flow cytometric analysis was used to detect CD11b membrane expression. RESULTS: Water soluble polysaccharides from Anv dose-dependently inhibited N-formyl-methionyl-leucyl-phenylalanine (fMLF)- and phorbol myristate acetate (PMA)-induced O(2) (.-) generation by human neutrophils. Moreover, Anv-polysaccharides strongly inhibited PMA-induced PKCβ and p47(phox) translocation to membranes and p47(phox) phosphorylation on Ser328, a main PKC target. In contrast, polysaccharides extract from Zygophyllum gaetulum plant, which is also used as a traditional North African medicine against inflammatory diseases, was ineffective on this PKCβ-p47phox pathway. Further, Anv inhibited important neutrophil degranulation markers corresponding to myeloperoxidase (MPO) release and CD11b membrane expression. CONCLUSION: The process of down-regulating NADPH oxidase by polysaccharides extracts from Anv provides new insights into the mechanism of Anv’s anti-inflammatory actions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12906-016-1411-7) contains supplementary material, which is available to authorized users.",2016 Nov 3,"['Boukemara, Hanane', 'Hurtado-Nedelec, Margarita', 'Marzaioli, Viviana', 'Bendjeddou, Dalila', 'El Benna, Jamel', 'Marie, Jean-Claude']",BMC Complement Altern Med,,,True
6c26acf9ba8059cbd9caa58acb1a64538cfb7df9,PMC,Two Genetically Similar H9N2 Influenza A Viruses Show Different Pathogenicity in Mice,http://dx.doi.org/10.3389/fmicb.2016.01737,PMC5096341,27867373,CC BY,"H9N2 Avian influenza virus has repeatedly infected humans and other mammals, which highlights the need to determine the pathogenicity and the corresponding mechanism of this virus for mammals. In this study, we found two H9N2 viruses with similar genetic background but with different pathogenicity in mice. The A/duck/Nanjing/06/2003 (NJ06) virus was highly pathogenic for mice, with a 50% mouse lethal dose (MLD(50)) of 10(2.83) 50% egg infectious dose (EID(50)), whereas the A/duck/Nanjing/01/1999 (NJ01) virus was low pathogenic for mice, with a MLD(50) of >10(6.81) EID(50). Further studies showed that the NJ06 virus grew faster and reached significantly higher titers than NJ01 in vivo and in vitro. Moreover, the NJ06 virus induced more severe lung lesions, and higher levels of inflammatory cellular infiltration and cytokine response in lungs than NJ01 did. However, only 12 different amino acid residues (HA-K157E, NA-A9T, NA-R435K, PB2-T149P, PB2-K627E, PB1-R187K, PA-L548M, PA-M550L, NP-G127E, NP-P277H, NP-D340N, NS1-D171N) were found between the two viruses, and all these residues except for NA-R435K were located in the known functional regions involved in interaction of viral proteins or between the virus and host factors. Summary, our results suggest that multiple amino acid differences may be responsible for the higher pathogenicity of the NJ06 virus for mice, resulting in lethal infection, enhanced viral replication, severe lung lesions, and excessive inflammatory cellular infiltration and cytokine response in lungs. These observations will be helpful for better understanding the pathogenic potential and the corresponding molecular basis of H9N2 viruses that might pose threats to human health in the future.",2016 Nov 4,"['Liu, Qingtao', 'Liu, Yuzhuo', 'Yang, Jing', 'Huang, Xinmei', 'Han, Kaikai', 'Zhao, Dongmin', 'Bi, Keran', 'Li, Yin']",Front Microbiol,,,True
9c6df064dc7aedea41eca964a69131e37f330f6b,PMC,"Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus)",http://dx.doi.org/10.1371/journal.pone.0166336,PMC5096705,27814404,CC BY,"In recent years, there has been a significant increase in detection of Enterovirus D-68 (EV-D68) among patients with severe respiratory infections worldwide. EV-D68 is now recognized as a re-emerging pathogen; however, due to lack of a permissive animal model for EV-D68, a comprehensive understanding of the pathogenesis and immune response against EV-D68 has been hampered. Recently, it was shown that EV-D68 has a strong affinity for α2,6-linked sialic acids (SAs) and we have shown previously that α2,6-linked SAs are abundantly present in the respiratory tract of cotton rats (Sigmodon hispidus). Thus, we hypothesized that cotton rats could be a potential model for EV-D68 infection. Here, we evaluated the ability of two recently isolated EV-D68 strains (VANBT/1 and MO/14/49), along with the historical prototype Fermon strain (ATCC), to infect cotton rats. We found that cotton rats are permissive to EV-D68 infection without virus adaptation. The different strains of EV-D68 showed variable infection profiles and the ability to produce neutralizing antibody (NA) upon intranasal infection or intramuscular immunization. Infection with the VANBT/1 resulted in significant induction of pulmonary cytokine gene expression and lung pathology. Intramuscular immunization with live VANBT/1 or MO/14/49 induced strong homologous antibody responses, but a moderate heterologous NA response. We showed that passive prophylactic administration of serum with high content of NA against VANBT/1 resulted in an efficient antiviral therapy. VANBT/1-immunized animals showed complete protection from VANBT/1 challenge, but induced strong pulmonary Th1 and Th2 cytokine responses and enhanced lung pathology, indicating the generation of exacerbated immune response by immunization. In conclusion, our data illustrate that the cotton rat is a powerful animal model that provides an experimental platform to investigate pathogenesis, immune response, anti-viral therapies and vaccines against EV-D68 infection.",2016 Nov 4,"['Patel, Mira C.', 'Wang, Wei', 'Pletneva, Lioubov M.', 'Rajagopala, Seesandra V.', 'Tan, Yi', 'Hartert, Tina V.', 'Boukhvalova, Marina S.', 'Vogel, Stefanie N.', 'Das, Suman R.', 'Blanco, Jorge C. G.']",PLoS One,,,True
430e499fc7f67e711312d57680f20c15a235cb20,PMC,Deep Sequencing Analysis Reveals the Mycoviral Diversity of the Virome of an Avirulent Isolate of Rhizoctonia solani AG-2-2 IV,http://dx.doi.org/10.1371/journal.pone.0165965,PMC5096721,27814394,CC BY,"Rhizoctonia solani represents an important plant pathogenic Basidiomycota species complex and the host of many different mycoviruses, as indicated by frequent detection of dsRNA elements in natural populations of the fungus. To date, eight different mycoviruses have been characterized in Rhizoctonia and some of them have been reported to modulate its virulence. DsRNA extracts of the avirulent R. solani isolate DC17 (AG2-2-IV) displayed a diverse pattern, indicating multiple infections with mycoviruses. Deep sequencing analysis of the dsRNA extract, converted to cDNA, revealed that this isolate harbors at least 17 different mycovirus species. Based on the alignment of the conserved RNA-dependent RNA-polymerase (RdRp) domain, this viral community included putative members of the families Narnaviridae, Endornaviridae, Partitiviridae and Megabirnaviridae as well as of the order Tymovirales. Furthermore, viruses, which could not be assigned to any existing family or order, but showed similarities to so far unassigned species like Sclerotinia sclerotiorum RNA virus L, Rhizoctonia solani dsRNA virus 1, Aspergillus foetidus slow virus 2 or Rhizoctonia fumigata virus 1, were identified. This is the first report of a fungal isolate infected by 17 different viral species and a valuable study case to explore the diversity of mycoviruses infecting R. solani.",2016 Nov 4,"['Bartholomäus, Anika', 'Wibberg, Daniel', 'Winkler, Anika', 'Pühler, Alfred', 'Schlüter, Andreas', 'Varrelmann, Mark']",PLoS One,,,True
bf6534fa1d3e5b2c6c5be7382633d56c6b92dea5,PMC,Viral respiratory infections in a nursing home: a six-month prospective study,http://dx.doi.org/10.1186/s12879-016-1962-8,PMC5097393,27814689,CC BY,"BACKGROUND: The knowledge on viral respiratory infections in nursing home (NH) residents and their caregivers is limited. The purpose of the present study was to assess and compare the incidence of acute respiratory infections (ARI) in nursing home (NH) residents and staff, to identify viruses involved in ARI and to correlate viral etiology with clinical manifestations of ARI. METHODS: The prospective surveillance study was accomplished in a medium-sized NH in Slovenia (central Europe). Ninety NH residents and 42 NH staff were included. Nasopharyngeal swabs were collected from all participants at enrollment (December 5th, 2011) and at the end of the study (May 31st, 2012), and from each participant that developed ARI within this timeframe. Molecular detection of 15 respiratory viruses in nasopharyngeal swab samples was performed. RESULTS: The weekly incidence rate of ARI in NH residents and NH staff correlated; however, it was higher in staff members than in residents (5.9 versus 3.8/1,000 person-days, P = 0.03), and was 2.5 (95 % CI: 1.36–4.72) times greater in residents without dementia than in residents with dementia. Staff members typically presented with upper respiratory tract involvement, whereas in residents lower respiratory tract infections predominated. Respiratory viruses were detected in 55/100 ARI episodes. In residents, influenza A virus, respiratory syncytial virus, and human metapneumovirus were detected most commonly, whereas in NH staff rhinovirus and influenza A virus prevailed. 38/100 ARI episodes (30/56 in residents, 8/44 in staff) belonged to one of three outbreaks (caused by human metapneumovirus, influenza A virus and respiratory syncytial virus, respectively). NH residents had higher chances for virus positivity within outbreak than HN staff (OR = 7.4, 95 % CI: 1.73–31.48, P < 0.01). CONCLUSIONS: ARI are common among NH residents and staff, and viruses were detected in a majority of the episodes of ARI. Many ARI episodes among NH residents were outbreak cases and could be considered preventable. TRIAL REGISTRATION: The study was registered on the 1(th) of December 2011 at ClinicalTrials (NCT01486160).",2016 Nov 4,"['Uršič, Tina', 'Miksić, Nina Gorišek', 'Lusa, Lara', 'Strle, Franc', 'Petrovec, Miroslav']",BMC Infect Dis,,,True
5a4a0f630530c7225fd23178fbdfedd2dccf535c,PMC,Antibacterial Effects of Glycyrrhetinic Acid and Its Derivatives on Staphylococcus aureus,http://dx.doi.org/10.1371/journal.pone.0165831,PMC5098735,27820854,CC BY,"Staphylococcus aureus is a major pathogen in humans and causes serious problems due to antibiotic resistance. We investigated the antimicrobial effect of glycyrrhetinic acid (GRA) and its derivatives against 50 clinical S. aureus strains, including 18 methicillin-resistant strains. The minimum inhibitory concentrations (MICs) of GRA, dipotassium glycyrrhizate, disodium succinoyl glycyrrhetinate (GR-SU), stearyl glycyrrhetinate and glycyrrhetinyl stearate were evaluated against various S. aureus strains. Additionally, we investigated the bactericidal effects of GRA and GR-SU against two specific S. aureus strains. DNA microarray analysis was also performed to clarify the mechanism underlying the antibacterial activity of GR-SU. We detected the antimicrobial activities of five agents against S. aureus strains. GRA and GR-SU showed strong antibacterial activities compared to the other three agents tested. At a higher concentration (above 2x MIC), GRA and GR-SU showed bactericidal activity, whereas at a concentration of 1x MIC, they showed a bacteriostatic effect. Additionally, GRA and GR-SU exhibited a synergistic effect with gentamicin. The expression of a large number of genes (including transporters) and metabolic factors (carbohydrates and amino acids) was altered by the addition of GR-SU, suggesting that the inhibition of these metabolic processes may influence the degree of the requirement for carbohydrates or amino acids. In fact, the requirement for carbohydrates or amino acids was increased in the presence of either GRA or GR-SU. GRA and GR-SU exhibited strong antibacterial activity against several S. aureus strains, including MRSA. This activity may be partly due to the inhibition of several pathways involved in carbohydrate and amino acid metabolism.",2016 Nov 7,"['Oyama, Kentaro', 'Kawada-Matsuo, Miki', 'Oogai, Yuichi', 'Hayashi, Tetsuya', 'Nakamura, Norifumi', 'Komatsuzawa, Hitoshi']",PLoS One,,,True
a106bdc3abdca61cda30b7f968c388e320e547e3,PMC,A data-driven model for influenza transmission incorporating media effects,http://dx.doi.org/10.1098/rsos.160481,PMC5098988,27853563,CC BY,"Numerous studies have attempted to model the effect of mass media on the transmission of diseases such as influenza; however, quantitative data on media engagement has until recently been difficult to obtain. With the recent explosion of ‘big data’ coming from online social media and the like, large volumes of data on a population’s engagement with mass media during an epidemic are becoming available to researchers. In this study, we combine an online dataset comprising millions of shared messages relating to influenza with traditional surveillance data on flu activity to suggest a functional form for the relationship between the two. Using this data, we present a simple deterministic model for influenza dynamics incorporating media effects, and show that such a model helps explain the dynamics of historical influenza outbreaks. Furthermore, through model selection we show that the proposed media function fits historical data better than other media functions proposed in earlier studies.",2016 Oct 26,"['Mitchell, Lewis', 'Ross, Joshua V.']",R Soc Open Sci,,,True
553190ac565fa3e5a93c4e52fb9d19157515ca06,PMC,A data-driven model for influenza transmission incorporating media effects,http://dx.doi.org/10.1098/rsos.160481,PMC5098988,27853563,CC BY,"Numerous studies have attempted to model the effect of mass media on the transmission of diseases such as influenza; however, quantitative data on media engagement has until recently been difficult to obtain. With the recent explosion of ‘big data’ coming from online social media and the like, large volumes of data on a population’s engagement with mass media during an epidemic are becoming available to researchers. In this study, we combine an online dataset comprising millions of shared messages relating to influenza with traditional surveillance data on flu activity to suggest a functional form for the relationship between the two. Using this data, we present a simple deterministic model for influenza dynamics incorporating media effects, and show that such a model helps explain the dynamics of historical influenza outbreaks. Furthermore, through model selection we show that the proposed media function fits historical data better than other media functions proposed in earlier studies.",2016 Oct 26,"['Mitchell, Lewis', 'Ross, Joshua V.']",R Soc Open Sci,,,False
20af160641510a4c79b9a23b06ea83d27ebba059,PMC,The nucleolar protein GLTSCR2 is required for efficient viral replication,http://dx.doi.org/10.1038/srep36226,PMC5099953,27824081,CC BY,"Glioma tumor suppressor candidate region gene 2 protein (GLTSCR2) is a nucleolar protein. In the investigation of the role of GLTSCR2 that played in the cellular innate immune response to viral infection, we found GLTSCR2 supported viral replication of rhabdovirus, paramyxovirus, and coronavirus in cells. Viral infection induced translocation of GLTSCR2 from nucleus to cytoplasm that enabled GLTSCR2 to attenuate type I interferon IFN-β and support viral replication. Cytoplasmic GLTSCR2 was able to interact with retinoic acid-inducible gene I (RIG-I) and the ubiquitin-specific protease 15 (USP15), and the triple interaction induced USP15 activity to remove K63-linked ubiquitination of RIG-I, leading to attenuation of RIG-I and IFN-β. Blocking cytoplasmic translocation of GLTSCR2, by deletion of its nuclear export sequence (NES), abrogated its ability to attenuate IFN-β and support viral replication. GLTSCR2-mediated attenuation of RIG-I and IFN-β led to alleviation of host cell innate immune response to viral infection. Our findings suggested that GLTSCR2 contributed to efficient viral replication, and GLTSCR2 should be considered as a potential target for therapeutic control of viral infection.",2016 Nov 8,"['Wang, Peng', 'Meng, Wen', 'Han, Shi-Chong', 'Li, Cui-Cui', 'Wang, Xiao-Jun', 'Wang, Xiao-Jia']",Sci Rep,,,True
73c97b301049429f21da128565e117ee1d368046,PMC,Brain on FIRES: Super Refractory Seizure in a 7 yr Old Boy,,PMC5100042,27843471,CC BY,"We present a 7 yr old boy afflicted with super-refractory seizure that responded poorly to antiepileptic drugs and sustained a long course of hospitalization and complications of high doses of medications as well as longstanding stay in hospital. The differential diagnoses were, fever-induced refractory epileptic encephalopathy (FIRES), and infectious and autoimmune encephalitis. However, work-ups had not revealed any evidence of any specific diagnosis, so we assumed that he was afflicted by viral infectious encephalitis as he had, fever, vomiting, and prodromal symptoms of infectious (most probably viral) disease prior to onset of the seizure attacks.",2016 Autumn,"['Tavasoli, Alireza', 'GHARIB, Behdad', 'ALIZADEH, Houman', 'FARSHADMOGHADDAM, Hossein', 'MEMARIAN, Sara', 'ASHRAFI, Mahmoodreza', 'SHARIFZADE, Meisam']",Iran J Child Neurol,,,True
36767ebe8e566a75a7fe9561206af5e722006b46,PMC,"Inosine pranobex is safe and effective for the treatment of subjects with confirmed acute respiratory viral infections: analysis and subgroup analysis from a Phase 4, randomised, placebo-controlled, double-blind study",http://dx.doi.org/10.1186/s12879-016-1965-5,PMC5100179,27821093,CC BY,"BACKGROUND: Inosine pranobex (Isoprinosine®) is an immunomodulatory drug approved in several countries for the treatment of viral infections. This study compared the efficacy and safety of inosine pranobex versus placebo in subjects with clinically diagnosed influenza-like illness, including subjects with laboratory-confirmed acute respiratory viral infections. Subgroup analyses evaluated the efficacy of inosine pranobex compared to placebo in otherwise healthy (without related ongoing disease) subjects that were less than 50 years of age and healthy subjects that were at least 50 years of age. The effect of body mass index (BMI) was evaluated in subjects less than 50 years of age. METHODS: A total of 463 subjects were randomly assigned to receive inosine pranobex (n = 231) or placebo (n = 232) in this Phase 4, randomised, double-blind, multicentre study. The primary efficacy endpoint was time to resolution of all influenza-like symptoms present at baseline to none. Safety was evaluated through analysis of adverse events, vital signs, and physical examinations. RESULTS: The difference in time to resolution of all influenza-like symptoms between treatment groups was not statistically significant but showed a faster improvement in subjects in the inosine pranobex group versus those in the placebo group - Hazard Ratio = 1.175; (95 % CI: 0.806–1.714). P-value = 0.324. In the subgroup analysis for subjects less than 50 years of age, statistically significant differences in time to resolution of influenza-like symptoms that favoured the inosine pranobex group over the placebo group were observed in those without related ongoing disease and those who were non-obese (BMI <30 kg/m(2)). The differences between the inosine pranobex and placebo groups in subjects at least 50 years of age without related ongoing disease and in subjects less than 50 years of age who were obese (BMI ≥30 kg/m(2)) were not statistically significant. Inosine pranobex was generally well tolerated, and no deaths were reported. CONCLUSIONS: The study results indicate the safety of inosine pranobex for the treatment of subjects with confirmed acute respiratory viral infections and confirm the efficacy of inosine pranobex versus placebo in healthy non-obese subjects less than 50 years of age with clinically diagnosed influenza-like illnesses. TRIAL REGISTRATION: EWO-ISO-2014/1, EudraCT 2014-001863-11; Date of registration: 29 APR 2014; Detail information web link: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001863-11/results ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1965-5) contains supplementary material, which is available to authorized users.",2016 Nov 7,"['Beran, Jiří', 'Šalapová, Eva', 'Špajdel, Marian', None]",BMC Infect Dis,,,True
10978f83e192204ea4f2347d49886969558a8b99,PMC,Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization,http://dx.doi.org/10.7554/eLife.17636,PMC5101012,27692070,CC BY,"Viral replicase recruitment and long-range RNA interactions are essential for RNA virus replication, yet the mechanism of their interplay remains elusive. Flaviviruses include numerous important human pathogens, e.g., dengue virus (DENV) and Zika virus (ZIKV). Here, we revealed a highly conserved, conformation-tunable cis-acting element named 5′-UAR-flanking stem (UFS) in the flavivirus genomic 5′ terminus. We demonstrated that the UFS was critical for efficient NS5 recruitment and viral RNA synthesis in different flaviviruses. Interestingly, stabilization of the DENV UFS impaired both genome cyclization and vRNA replication. Moreover, the UFS unwound in response to genome cyclization, leading to the decreased affinity of NS5 for the viral 5′ end. Thus, we propose that the UFS is switched by genome cyclization to regulate dynamic RdRp binding for vRNA replication. This study demonstrates that the UFS enables communication between flavivirus genome cyclization and RdRp recruitment, highlighting the presence of switch-like mechanisms among RNA viruses. DOI: http://dx.doi.org/10.7554/eLife.17636.001",,"['Liu, Zhong-Yu', 'Li, Xiao-Feng', 'Jiang, Tao', 'Deng, Yong-Qiang', 'Ye, Qing', 'Zhao, Hui', 'Yu, Jiu-Yang', 'Qin, Cheng-Feng']",eLife.; 5:e17636,,,True
4f2e6240097fc7f8699ec07c84d37bbc8a15310c,PMC,Acyclic nucleoside phosphonates containing the amide bond,http://dx.doi.org/10.1007/s00706-016-1848-x,PMC5101293,27881885,CC BY,"ABSTRACT: To study the influence of a linker rigidity and donor–acceptor properties, the P–CH(2)–O–CHR– fragment in acyclic nucleoside phosphonates (e.g., acyclovir, tenofovir) was replaced by the P–CH(2)–HN–C(O)– residue. The respective phosphonates were synthesized in good yields by coupling the straight chain of ω-aminophosphonates and nucleobase-derived acetic acids with EDC. Based on the (1)H and (13)C NMR data, the unrestricted rotation within the methylene and 1,2-ethylidene linkers in phosphonates from series a and b was confirmed. For phosphonates containing 1,3-propylidene (series c) fragments, antiperiplanar disposition of the bulky O,O-diethylphosphonate and substituted amidomethyl groups was established. The synthesized ANPs P–X–HNC(O)–CH(2)B (X = CH(2), CH(2)CH(2), CH(2)CH(2)CH(2), CH(2)OCH(2)CH(2)) appeared inactive in antiviral assays against a wide variety of DNA and RNA viruses at concentrations up to 100 μM while marginal antiproliferative activity (L1210 cells, IC(50) = 89 ± 16 μM and HeLa cells, IC(50) = 194 ± 19 μM) was noticed for the analog derived from (5-fluorouracyl-1-yl)acetic acid and O,O-diethyl (2-aminoethoxy)methylphosphonate. GRAPHICAL ABSTRACT: [Image: see text]",2016 Oct 26,"['Głowacka, Iwona E.', 'Piotrowska, Dorota G.', 'Andrei, Graciela', 'Schols, Dominique', 'Snoeck, Robert', 'Wróblewski, Andrzej E.']",Monatsh Chem,,,True
281ed09feadb379021bb0d63faa25b484ca482f1,PMC,Predictors of recovery from post-traumatic stress disorder after the dongting lake flood in China: a 13–14 year follow-up study,http://dx.doi.org/10.1186/s12888-016-1097-x,PMC5101704,27825328,CC BY,"BACKGROUND: Floods are some of the most common and destructive natural disasters in the world, potentially leading to both physical injuries and psychological disorders, including post-traumatic stress disorder (PTSD). PTSD can damage functional capacity and interfere with social functioning. However, little is known about recovery from PTSD after floods. This study used 2013–2014 follow-up data on survivors of the 1998 Dongting Lake flood who were diagnosed with PTSD in 2000 to measure the prevalence rate of PTSD at follow-up and identify predictors of recovery from the PTSD diagnosis in 2000. METHODS: Participants included survivors who had been diagnosed as having PTSD in 2000 after the 1998 Dongting Lake flood. PTSD at follow-up was reassessed using the PTSD Checklist-Civilian version. Information on demographics, trauma-related stressors, post-trauma stressors, social support, and coping style were collected through face-to-face interviews. The association between the independent variables and PTSD at follow-up was analyzed using logistic regression analyses. RESULTS: A total of 201 participants with a PTSD diagnosis in 2000 were included in this study. A total of 19.4 % of the flood survivors with PTSD in 2000 continued to suffer from PTSD in 2013–2014. In the multivariable logistic regression model, individuals who had lost relatives (OR = 12.37, 95 % CI = 2.46–62.16), suffered from bodily injury (OR = 5.01, 95 % CI = 1.92–13.08), had a low level of social support (OR = 5.47, 95 % CI = 1.07–27.80), or had a negative coping style (OR = 4.92, 95 % CI = 1.89–12.81) were less likely to recover from PTSD. CONCLUSIONS: The prevalence rate of PTSD at follow-up indicates that natural disasters such as floods may have a negative influence on survivors’ mental health for an extended period of time. Individuals who have lost relatives, suffered from bodily injury, had a low level of social support, or had a negative coping style were less likely to recover from PTSD. Therefore, effective psychological intervention measures are necessary for facilitating the recovery process from PTSD, especially for individuals with adverse prognostic factors.",2016 Nov 8,"['Dai, Wenjie', 'Wang, Jieru', 'Kaminga, Atipatsa C.', 'Chen, Long', 'Tan, Hongzhuan', 'Lai, Zhiwei', 'Deng, Jing', 'Liu, Aizhong']",BMC Psychiatry,,,True
00ccc4ef2b6c6f238836b7feb5123bd6a822cc08,PMC,Involvement of the different lung compartments in the pathogenesis of pH1N1 influenza virus infection in ferrets,http://dx.doi.org/10.1186/s13567-016-0395-0,PMC5101722,27825367,CC BY,"Severe cases after pH1N1 infection are consequence of interstitial pneumonia triggered by alveolar viral replication and an exacerbated host immune response, characterized by the up-regulation of pro-inflammatory cytokines and the influx of inflammatory leukocytes to the lungs. Different lung cell populations have been suggested as culprits in the unregulated innate immune responses observed in these cases. This study aims to clarify this question by studying the different induction of innate immune molecules by the distinct lung anatomic compartments (vascular, alveolar and bronchiolar) of ferrets intratracheally infected with a human pH1N1 viral isolate, by means of laser microdissection techniques. The obtained results were then analysed in relation to viral quantification in the different anatomic areas and the histopathological lesions observed. More severe lung lesions were observed at 24 h post infection (hpi) correlating with viral antigen detection in bronchiolar and alveolar epithelial cells. However, high levels of viral RNA were detected in all anatomic compartments throughout infection. Bronchiolar areas were the first source of IFN-α and most pro-inflammatory cytokines, through the activation of RIG-I. In contrast, vascular areas contributed with the highest induction of CCL2 and other pro-inflammatory cytokines, through the activation of TLR3. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0395-0) contains supplementary material, which is available to authorized users.",2016 Nov 8,"['Vidaña, Beatriz', 'Martínez, Jorge', 'Martorell, Jaime', 'Montoya, María', 'Córdoba, Lorena', 'Pérez, Mónica', 'Majó, Natàlia']",Vet Res,,,True
aee43bea8ff949773e7d22ebbfd6304c20c2a76d,PMC,Discovery and Partial Genomic Characterisation of a Novel Nidovirus Associated with Respiratory Disease in Wild Shingleback Lizards (Tiliqua rugosa),http://dx.doi.org/10.1371/journal.pone.0165209,PMC5102451,27828982,CC BY,"A respiratory disease syndrome has been observed in large numbers of wild shingleback lizards (Tiliqua rugosa) admitted to wildlife care facilities in the Perth metropolitan region of Western Australia. Mortality rates are reportedly high without supportive treatment and care. Here we used next generation sequencing techniques to screen affected and unaffected individuals admitted to Kanyana Wildlife Rehabilitation Centre in Perth between April and December 2015, with the resultant discovery of a novel nidovirus significantly associated with cases of respiratory disease according to a case definition based on clinical signs. Interestingly this virus was also found in 12% of apparently healthy individuals, which may reflect testing during the incubation period or a carrier status, or it may be that this agent is not causative in the disease process. This is the first report of a nidovirus in lizards globally. In addition to detection of this virus, characterisation of a 23,832 nt segment of the viral genome revealed the presence of characteristic nidoviral genomic elements providing phylogenetic support for the inclusion of this virus in a novel genus alongside Ball Python nidovirus, within the Torovirinae sub-family of the Coronaviridae. This study highlights the importance of next generation sequencing technologies to detect and describe emerging infectious diseases in wildlife species, as well as the importance of rehabilitation centres to enhance early detection mechanisms through passive and targeted health surveillance. Further development of diagnostic tools from these findings will aid in detection and control of this agent across Australia, and potentially in wild lizard populations globally.",2016 Nov 9,"['O’Dea, Mark A.', 'Jackson, Bethany', 'Jackson, Carol', 'Xavier, Pally', 'Warren, Kristin']",PLoS One,,,True
b0cedaf41c2c857fcc792117c6bb3df1a87bc544,PMC,Interferon-Stimulated Gene 15 Conjugation Stimulates Hepatitis B Virus Production Independent of Type I Interferon Signaling Pathway In Vitro,http://dx.doi.org/10.1155/2016/7417648,PMC5102744,27867263,CC BY,"Hepatitis B virus (HBV) is an important account of infectious hepatitis and interferon (IFN) remains one of the best treatment options. Activation of type I IFN signaling pathway leads to expressions of IFN-stimulated genes (ISGs) which play important roles in antiviral and immunomodulatory responses to HBV or hepatitis C virus (HCV) infection. Our previous studies indicated that ISG15 and its conjugation (ISGylation) were exploited by HCV to benefit its replication and persistent infection. This study was designed to assess the role of ISG15 and ISGylation in HBV infection in vitro. The levels of ISG15 and ISGylation were upregulated by ISG15 plasmid transfection into HepG2.2.15 cells. Decreased ISGylation was achieved by siRNA targeting UBE1L, the only E1 activating enzyme for ISGylation. Overexpression of ISG15 and subsequent ISGylation significantly increased the levels of HBV DNA in the culture supernatants although the intracellular viral replication remained unaffected. Silencing UBE1L, with decreased ISGylation achieved, abrogated this ISGylation-mediated promoting effect. Our data indicated that overexpression of ISG15 stimulated HBV production in an ISGylation-dependent manner. Identification of ISG15-conjugated proteins (either HBV viral or host proteins) may reveal promising candidates for further antiviral drug development.",2016 Oct 27,"['Li, Yujia', 'Li, Shilin', 'Duan, Xiaoqiong', 'Chen, Yanzhao', 'Jiao, Baihai', 'Ye, Haiyan', 'Yao, Min', 'Chen, Limin']",Mediators Inflamm,,,False
05e9af5c04c17b89fd8d65d62a381eb22e8316ed,PMC,Interferon-Stimulated Gene 15 Conjugation Stimulates Hepatitis B Virus Production Independent of Type I Interferon Signaling Pathway In Vitro,http://dx.doi.org/10.1155/2016/7417648,PMC5102744,27867263,CC BY,"Hepatitis B virus (HBV) is an important account of infectious hepatitis and interferon (IFN) remains one of the best treatment options. Activation of type I IFN signaling pathway leads to expressions of IFN-stimulated genes (ISGs) which play important roles in antiviral and immunomodulatory responses to HBV or hepatitis C virus (HCV) infection. Our previous studies indicated that ISG15 and its conjugation (ISGylation) were exploited by HCV to benefit its replication and persistent infection. This study was designed to assess the role of ISG15 and ISGylation in HBV infection in vitro. The levels of ISG15 and ISGylation were upregulated by ISG15 plasmid transfection into HepG2.2.15 cells. Decreased ISGylation was achieved by siRNA targeting UBE1L, the only E1 activating enzyme for ISGylation. Overexpression of ISG15 and subsequent ISGylation significantly increased the levels of HBV DNA in the culture supernatants although the intracellular viral replication remained unaffected. Silencing UBE1L, with decreased ISGylation achieved, abrogated this ISGylation-mediated promoting effect. Our data indicated that overexpression of ISG15 stimulated HBV production in an ISGylation-dependent manner. Identification of ISG15-conjugated proteins (either HBV viral or host proteins) may reveal promising candidates for further antiviral drug development.",2016 Oct 27,"['Li, Yujia', 'Li, Shilin', 'Duan, Xiaoqiong', 'Chen, Yanzhao', 'Jiao, Baihai', 'Ye, Haiyan', 'Yao, Min', 'Chen, Limin']",Mediators Inflamm,,,True
adc882dda7e73073791ae83afee7affd0d3e3793,PMC,Cytokine cascade and networks among MSM HIV seroconverters: implications for early immunotherapy,http://dx.doi.org/10.1038/srep36234,PMC5103227,27830756,CC BY,"The timing, intensity and duration of the cytokine cascade and reorganized interrelations in cytokine networks are not fully understood during acute HIV-1 infection (AHI). Using sequential plasma samples collected over three years post-infection in a cohort of MSM HIV-1 seroconvertors, we determined the early kinetics of cytokine levels during FiebigI-IV stages using Luminex-based multiplex assays. Cytokines were quantified and relationships between cytokines were assessed by Spearman correlation. Compared with HIV-negative MSM, HIV-infected individuals had significantly increased multiple plasma cytokines, including GM-CSF, IFN-α2, IL-12p70, IP-10 and VEGF, during both acute and chronic stages of infection. Furthermore, rapid disease progressors (RDPs) had earlier and more robust cytokine storms, compared with slow disease progressors (SDPs) (49.6 days vs. 74.9 days, respectively; 6.7-fold vs. 3.7-fold change of cytokines, respectively), suggesting the faster and stronger cytokine storm during AHI could promote disease progression. On the other hand, HIV-1 infection induced more interlocked cytokines network, establishing new strong correlations and imposing a higher rigidity. There were, respectively, 146 (44.9%) statistically significant correlations of cytokines in RDPs and 241 (74.2%) in SDPs (p < 0.001). This study suggests that immunomodulatory interventions aimed at controlling cytokine storm in AHI may be beneficial to slow eventual disease progression.",2016 Nov 10,"['Huang, Xiaojie', 'Liu, Xinchao', 'Meyers, Kathrine', 'Liu, Lihong', 'Su, Bin', 'Wang, Pengfei', 'Li, Zhen', 'Li, Lan', 'Zhang, Tong', 'Li, Ning', 'Chen, Hui', 'Li, Haiying', 'Wu, Hao']",Sci Rep,,,True
37aa23b999728b605b38892e8cedff6100c85a82,PMC,Cytokine cascade and networks among MSM HIV seroconverters: implications for early immunotherapy,http://dx.doi.org/10.1038/srep36234,PMC5103227,27830756,CC BY,"The timing, intensity and duration of the cytokine cascade and reorganized interrelations in cytokine networks are not fully understood during acute HIV-1 infection (AHI). Using sequential plasma samples collected over three years post-infection in a cohort of MSM HIV-1 seroconvertors, we determined the early kinetics of cytokine levels during FiebigI-IV stages using Luminex-based multiplex assays. Cytokines were quantified and relationships between cytokines were assessed by Spearman correlation. Compared with HIV-negative MSM, HIV-infected individuals had significantly increased multiple plasma cytokines, including GM-CSF, IFN-α2, IL-12p70, IP-10 and VEGF, during both acute and chronic stages of infection. Furthermore, rapid disease progressors (RDPs) had earlier and more robust cytokine storms, compared with slow disease progressors (SDPs) (49.6 days vs. 74.9 days, respectively; 6.7-fold vs. 3.7-fold change of cytokines, respectively), suggesting the faster and stronger cytokine storm during AHI could promote disease progression. On the other hand, HIV-1 infection induced more interlocked cytokines network, establishing new strong correlations and imposing a higher rigidity. There were, respectively, 146 (44.9%) statistically significant correlations of cytokines in RDPs and 241 (74.2%) in SDPs (p < 0.001). This study suggests that immunomodulatory interventions aimed at controlling cytokine storm in AHI may be beneficial to slow eventual disease progression.",2016 Nov 10,"['Huang, Xiaojie', 'Liu, Xinchao', 'Meyers, Kathrine', 'Liu, Lihong', 'Su, Bin', 'Wang, Pengfei', 'Li, Zhen', 'Li, Lan', 'Zhang, Tong', 'Li, Ning', 'Chen, Hui', 'Li, Haiying', 'Wu, Hao']",Sci Rep,,,False
250c1f24a22bcb81973ea532f8236838987e0872,PMC,"The 12th Edition of the Scientific Days of the National Institute for Infectious Diseases “Prof. Dr. Matei Bals” and the 12th National Infectious Diseases Conference: Bucharest, Romania. 23–25 November 2016",http://dx.doi.org/10.1186/s12879-016-1877-4,PMC5103241,,CC BY,"A1 The outcome of patients with recurrent versus non-recurrent pneumococcal meningitis in a tertiary health-care hospital in Bucharest Cristian-Mihail Niculae, Eliza Manea, Raluca Jipa, Simona Merisor, Ruxandra Moroti, Serban Benea, Adriana Hristea A2 Influence of bacteriophages on sessile Gram-positive and Gram-negative bacteria Alina Cristina Neguț, Oana Săndulescu, Anca Streinu-Cercel, Dana Mărculescu, Magdalena Lorena Andrei, Veronica Ilie, Marcela Popa, Coralia Bleotu, Carmen Chifiriuc, Mircea Ioan Popa, Adrian Streinu-Cercel A3 The utility of inflammatory biomarkers in the prognostic evaluation of septic patients – past, present and future Alina Orfanu, Cristina Popescu, Anca Leuștean, Remulus Catană, Anca Negru, Alexandra Badea, Radu Orfanu, Cătălin Tilișcan, Victoria Aramă, Ştefan Sorin Aramă A4 Etiologic and clinical features of bacterial meningitis in infants Constanța-Angelica Vișan, Anca-Cristina Drăgănescu, Anuța Bilașco, Camelia Kouris, Mădălina Merișescu, Magdalena Vasile, Diana-Maria Slavu, Sabina Vintilă, Endis Osman, Alina Oprea, Sabina Sandu, Monica Luminos A5 The diagnostic and prognostic role of neutrophil to lymphocyte count ratio in sepsis Alina Orfanu, Victoria Aramă, Ştefan Sorin Aramă, Anca Leuştean, Remulus Catană, Anca Negru, Gabriel Adrian Popescu, Cristina Popescu A6 Whooping cough in a HIV positive patient Ramona Georgiana Stanculete, Ana Vaduva Enoiu, Adelina Raluca Marinescu, Voichita Lazureanu A7 Cronobacter sakazakii sepsis in varicella patient Adelina-Raluca Marinescu, Alexandru Crișan, Voichița Lăzureanu, Virgil Musta, Narcisa Nicolescu, Ruxandra Laza A8 Anaerobes an underdiagnosed cause of prosthesis joint infection Anca-Ruxandra Negru, Daniela-Ioana Munteanu, Raluca Mihăilescu, Remulus Catană, Olga Dorobăț, Alexandru Rafila, Emilia Căpraru, Marius Niculescu, Rodica Marinescu, Olivera Lupescu, Vlad Predescu, Adrian Streinu-Cercel, Victoria Aramă, Daniela Tălăpan A9 Streptococcus pneumoniae meningitis presenting with normal CSF – case presentation Ramona Ștefania Popescu, Luminița Bradu, Dragoș Florea, Adrian Streinu-Cercel A10 Extrapulmonary manifestations of infection with Mycoplasma pneumoniae – study on 24 cases Daniela Anicuta Leca, Elena Bunea, Andra Teodor, Egidia Miftode A11 The molecular diagnosis of severe bacterial sepsis in pediatric population Mădălina Merișescu, Gheorghiță Jugulete, Adrian Streinu-Cercel, Dragoș Florea, Monica Luminos A12 Acute Staphylococcus aureus endocarditis with multiple septic complications in a patient with diabetes mellitus – case presentation Ramona Ștefania Popescu, Anamaria Dobrotă, Adina Ilie, Liliana Lucia Preoțescu A13 Is Streptococcus suis meningitis an under-diagnosed zoonosis? Adriana Hristea, Raluca Jipa, Nicoleta Irimescu, Irina Panait, Eliza Manea, Simona Merisor, Cristian Niculae, Daniela Tălăpan A14 Klebsiella pneumoniae isolated from blood. Antimicrobial resistance – past and present Liana Cătălina Gavriliu, Otilia Elisabeta Benea, Șerban Benea, Alexandru Rafila, Olga Dorobăț, Mona Popoiu A15 Antibiotics resistance in Staphylococcus aureus isolated from blood cultures Livia Dragonu, Augustin Cupşa, Iulian Diaconescu, Irina Niculescu, Lucian Giubelan, Florentina Dumitrescu, Andreea Cristina Stoian, Camelia Guţă, Simona Puiu A16 Predominance of CTX-M enzymes in extended-spectrum β-lactamase-producing Enterobacteriaceae in two hospitals of Quebec City Bunescu Irina, Marilyse Vallée, Ann Huletsky, Dominique K. Boudreau, Ève Bérubé, Richard Giroux, Jean Longtin, Yves Longtin, Michel G. Bergeron A17 Postoperative meningoencephalitis with Acinetobacter baumannii XDR – a therapeutic challenge - Case report Cleo Nicoleta Roșculeț, Dalila-Ana Toma, Catrinel Ciuca, Daniela Tălăpan, Cătălin Apostolescu, Andrei Rogoz, Andrei Stangaciu, Viorica Mitescu, Tudor Vladoiu, Doina Iovănescu A18 Septic arthritis with Burkholderia cepacia Michaela Oana, Simona Costin A19 A novel approach for managing hard-to-treat infections Alina Cristina Neguț, Oana Săndulescu, Anca Streinu-Cercel, Maria Magdalena Moțoi, Mircea Ioan Popa, Adrian Streinu-Cercel A20 Nineteen months surveillance for multidrug resistant organisms (MDRO) by detecting asymptomatic colonization Daniela Tălăpan, Olga Mihaela Dorobăț, Mona Popoiu, Alexandru Mihai, Doina Iovănescu, Cleo Roşculeț, Cătălin Apostolescu, Gabriel-Adrian Popescu, Adrian Abagiu, Ruxandra Moroti-Constantinescu, Adriana Hristea, Victoria Aramă, Otilia Benea, Mădălina Simoiu, Rodica Bacruban, Adrian Streinu-Cercel, Alexandru Rafila A21 Antimicrobial resistance of Gram-positive cocci isolated from clinical specimens in the National Institute of Infectious Diseases “Prof Dr. Matei Balș” between 2009–2015 Olga Mihaela Dorobăț, Daniela Tălăpan, Alexandru Mihai, Ioana Bădicuț, Mona Popoiu, Alina Borcan, Alexandru Rafila A22 The high percentage of carbapenem-resistant Gram-negative bacilli in Romania: an analysis and some proposals Gabriel Adrian Popescu A23 Etiological, clinical and therapeutic considerations on 78 cases of healthcare associated meningitis or ventriculitis admitted in the “Sf. Parascheva” infectious diseases clinical hospital, Iași, from 2011 to 2015 Mihnea Hurmuzache, Georgiana Enache, Alexandra Ciocan, Mircea Bararu, Madalina Popazu A24 Nosocomial infection dynamics in an Intensive Care Department – an overview (epidemiological and clinical monitoring, advanced therapeutic intervention). Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz Cătălin Gabriel Apostolescu, Viorica Mitescu(,) Tudor Vladoiu, Dalila Toma, Catrinel Ciuca A25 Safety and efficacy of interferon free treatment in patients with HCV chronic hepatitis- experience of a single Internal Medicine center Laura Iliescu, Georgiana Minzala, Letitia Toma, Mihaela Baciu, Alina Tanase, Carmen Orban A26 Viusid in treatment of chronic viral hepatitis B and C Victor Pantea, Gheorghe Placinta, Valentin Cebotarescu, Lilia Cojuhari, Paulina Jimbei A27 The management of hyperbilirubinemia in HCV cirrhotic patients who underwent therapy with direct acting antivirals Cristina Popescu, Anca Leuștean, Cristina Dragomirescu, Alina Orfanu, Cristina Murariu, Laurențiu Stratan, Alexandra Badea, Cătălin Tilișcan, Daniela Munteanu, Raluca Năstase, Violeta Molagic, Mihaela Rădulescu, Remulus Catana, Victoria Aramă A28 The efficacy of ombitasvir-paritaprevir/ritonavir, dasabuvir and ribavirin in patients with genotype 1 HCV compensated cirrhosis Cristina Popescu, Laurențiu Stratan, Remulus Catana, Anca Leuștean, Cristina Dragomirescu, Alexandra Badea, Cristina Murariu, Raluca Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Mihaela Rădulescu, Alina Orfanu, Ioan Diaconu, Anca Negru, Iulia Bodosca, Violeta Niță, Victoria Aramă A29 The efficacy of direct acting antivirals regimen without ribavirin in HCV genotype 1b infected patients with compensated cirrhosis Anca Leuștean, Victoria Aramă, Alina Orfanu, Remulus Catana, Laurențiu Stratan, Cristina Dragomirescu, Cristina Murariu, Alexandra Badea, Cătălin Tilișcan, Daniela Munteanu, Violeta Molagic, Raluca Năstase, Mihaela Rădulescu, Cristina Popescu A30 Liver decompensation during ombitasvir-paritaprevir/ritonavir-dasabuvir and ribavirin regimen in HCV infected patients with Child-Pugh A cirrhosis Cristina Popescu, Cristina Dragomirescu, Anca Leuștean, Cristina Murariu, Laurențiu Stratan, Alexandra Badea, Remulus Catană, Alina Orfanu, Raluca Mihaela Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Victoria Aramă A31 The safety of direct acting antivirals in HCV compensated cirrhotic patients - an interim analysis Victoria Aramă, Remulus Catană, Cristina Dragomirescu, Cristina Murariu, Anca Leuștean, Laurențiu Stratan, Alexandra Badea, Alina Orfanu, Anca Negru, Raluca Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Mihaela Rădulescu, Ioan Diaconu, Violeta Niță, Iulia Bodoșca, Cristina Popescu A32 The access of patients with HCV compensated cirrhosis to the National Program of therapy with direct acting antivirals Cristina Popescu, Alexandra Badea, Anca Leuștean, Alina Orfanu, Anca Negru, Laurențiu Stratan, Cristina Dragomirescu, Remulus Catană, Cristina Murariu, Violeta Molagic, Raluca Năstase, Cătălin Tilișcan, Daniela Munteanu, Mihaela Rădulescu, Ioan Diaconu, Violeta Niță, Iulia Bodoșca, Victoria Aramă A33 Severe reactivation of chronic hepatitis B after discontinuation of nucleos(t)ide analogues – a case series Cristina Popescu, Alina Orfanu, Anca Leuștean, Alexandra Badea, Laurențiu Stratan, Remulus Catană, Cătălin Tilișcan, Victoria Aramă A34 The dynamic of hematological disorders during direct acting antivirals therapy for HCV compensated cirrhosis Cristina Popescu, Cristina Murariu, Cristina Dragomirescu, Anca Leuștean, Laurențiu Stratan, Alina Orfanu, Alexandra Badea, Remulus Catană, Anca Negru, Cătălin Tilișcan, Daniela Munteanu, Mihaela Rădulescu, Violeta Molagic, Raluca Mihaela Năstase, Ioan Alexandru Diaconu, Iulia Bodoșca, Violeta Niță, Victoria Aramă A35 Behaviors, attitudes and risk factors for viral hepatitis in international medical students vs. the general population in Romania Yagmur Erturk, Oana Săndulescu, Alina Cristina Neguț, Claudiu Mihai Șchiopu, Adrian Streinu-Cercel, Anca Streinu-Cercel A36 Characteristics of hepatitis C virus reactivation due to immunosuppressive therapy in Romanian HCV infected patients with hematological malignancies Violeta Molagic, Cătălin Tilișcan, Cristina Popescu, Raluca Mihăilescu, Daniela Munteanu, Raluca Năstase, Anca Negru, Angelica Tenita, Victoria Aramă, Ștefan Sorin Aramă A37 The dynamic IFN-gamma serum levels during successful peginterferon-a 2a/ribavirin therapy in HCV chronic infection Simona Alexandra Iacob, Diana Gabriela Iacob, Monica Luminos A38 Overlapping risk factors for transmission of HBV, HCV and HIV in the general population in Romania Anca Streinu-Cercel, Oana Săndulescu, Mioara Predescu, Alexandra Mărdărescu, Cătălin Tilișcan, Mihai Săndulescu, Claudiu Mihai Șchiopu, Adrian Streinu-Cercel A39 Acute hepatitis - an uncommon neurological complication Cleo Nicoleta Roșculeț, Catrinel Olimpia Ciuca, Dalila Ana Toma, Cătălin Gabriel Apostolescu, Andrei Rogoz, Cristina Elena Mitu, Andrei Stangaciu, Viorica Daniela Mitescu, Tudor Gheorghe Vladoiu, Doina Viorica Iovănescu A40 Regression of liver fibrosis following sustained virological response in patients with chronic HCV infection and cirrhosis Oana Săndulescu, Anca Streinu-Cercel, Monica Andreea Stoica, Liliana Lucia Preoțescu, Daniela Manolache, Gabriela Jana Ceapraga, Maria Magdalena Moțoi, Luminița Bradu, Adina Ilie, Gabriela Mircea, Ionel Durbală, Adrian Streinu-Cercel A41 Preliminary results of treatment with sofosbuvir and daclatasvir of patients with chronic hepatitis C Irina Russu, Tiberiu Holban, Tatiana Pantilimonov, Galina Chiriacov, Arcadie Macvovei, Elena Scorohodico, Oleg Dmitriev A42 HIV-syphilis coinfection Diana Alexandra Costache, Anca Benea, Eliza Manea, Cristian Niculae, Raluca Jipa, Adriana Hristea, Elisabeta Benea, Ruxandra Moroti, Șerban Benea A43 Thrombophilia – additional risk factor for the evolution of pregnancy in HIV-positive patients Mihai Mitran, Carmen Georgescu, Loredana Mitran, Simona Vladareanu A44 The incidence of oropharyngeal candidiasis in hospitalized HIV infected pediatric Romanian cohort between 1 January - 31 December 2015 Andreea Ioana Magirescu, Viorica Andreev, Cristina Nicolau, Alexandra Largu, Carmen Dorobat, Carmen Manciuc A45 TB incidence in HIV infected patients during the year of 2015 Viorica Andreev, Andreea Ioana Magirescu, Ina Isac, Cristina Nicolau, Alexandra Largu, Carmen Dorobat, Carmen Manciuc A46 Retrospective analysis of HIV/AIDS deaths recorded in the Clinical Infectious Diseases Hospital, Constanța in the period 01 January 2014–30 June 2016. Epidemiological considerations. Iulia Gabriela Șerban, Ghiulendan Resul, Consuela Marcaș A47 Acute liver failure with favorable evolution in an HIV-HBV coinfected patient Iosif Marincu, Patricia Poptelecan, Bogdan Trincă, Sorina Mitrescu, Anca Tudor, Daliborca Vlad, Livius Tirnea A48 Lifestyle impact on HIV management Nurcan Baydaroglu, Alina Cristina Neguț, Oana Săndulescu, Daniela Manolache, Gabriela Ceapraga, Monica Andreea Stoica, Anca Streinu-Cercel, Adrian Streinu-Cercel 49. HIV positive mothers newborns - clinical experience from January 2012 to June 2016 Carmen Manciuc, Mariana Pagute, Cristina Nicolau, Carmen Dorobăț, Alexandra Largu A50 Rediscovering HIV-associated progressive multifocal leukoencephalopathy and HIV encephalopathy: clinical suspicion and subsequent brain autopsies Ioan-Alexandru Diaconu, Laurențiu Stratan, Daniela Ion, Luciana Nichita, Cristina Popescu, Raluca Năstase, Daniela Munteanu, Violeta Molagic, Cătălin Tilișcan, Mihaela Rădulescu, Alexandra Diaconu, Anca Negru, Alina Orfanu, Cristina Dragomirescu, Remulus Catană, Anca Leuștean, Irina Duport-Dodot, Cristina Murariu, Iulia Bodoșca, Violeta Niță, Alexandra Badea, Victoria Aramă A51 Antenatal surveillance of pregnant women with risk behavior and its impact on mother-to-child HIV transmission in Romania Mariana Mărdărescu, Cristina Petre, Marieta Iancu, Rodica Ungurianu, Alina Cibea, Ruxandra Drăghicenoiu, Ana Maria Tudor, Delia Vlad, Sorin Petrea, Carina Matei, Dan Oțelea, Carmen Crăciun, Cristian Anghelina, Alexandra Mărdărescu A52 Noninvasive assessments (APRI, Fib-4, transient elastography) of fibrosis in patients with HIV and HIV/HBV infection Elena Dumea, Adrian Streinu-Cercel, Sorin Rugină, Lucian Cristian Petcu, Stela Halichidis, Simona Claudia Cambrea A53 Undetectable HIV viral load – the main goal in the management of HIV-infected patients Carmen Chiriac, Nina-Ioana Bodnar, Iringo-Erzsebet Zaharia-Kezdi, Cristina Gîrbovan, Andrea Incze, Anca Meda Georgescu A54 LPS serum levels and correlation with immunological, virological and clinical outcome in HIV infected patients Simona Alexandra Iacob, Diana Gabriela Iacob, Eugenia Panaitescu, Monica Luminos, Manole Cojocaru A55 LL37 human cathelicidin serum levels are positively correlated with IFN gamma and alanine aminotransferase level in HCV infection Simona Alexandra Iacob, Diana Gabriela Iacob, Monica Luminos A56 Early diagnosis of pulmonary tuberculosis in a non-compliant HIV/AIDS late presenter patient Vochita Laurențiu, Vochita Andreia, Opreanu Radu, Trinca Bogdan, Rosca Ovidiu, Marincu Iosif A57 Evolution of antiretroviral regimens in naϊve patients in 2016 Ramona Zamfir, Alina Angelescu, Alena Andreea Popa, Raluca Jipa, Ruxandra Moroti, Adriana Hristea, Liana Gavriliu, Șerban Benea, Elisabeta Benea A58 The unfavorable risk factors for HIV infected persons with positive blood cultures hospitalized at the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” in 2015 Alena-Andreea Popa, Georgeta Ducu, Daniela Camburu, Alina Cozma, Manuela Podani, Roxana Dumitriu, Liana Gavriliu, Șerban Benea, Elisabeta Benea A59 Epidemiological aspects of HIV infection in Oltenia region Andreea Cristina Stoian, Florentina Dumitrescu, Augustin Cupșa, Lucian Giubelan, Irina Niculescu, Loredana Ionescu, Livia Dragonu A60 HIV risk behaviors and prevalence among patients in methadone maintenance therapy (MMT) from Arena center, Bucharest Adrian Octavian Abagiu, Loredana Nicoleta Stoica, Catrinel Blaga, Archontis Koulosousas, Roxana Ștefănescu, Alice Atomoaie, Florentina Paraschiv, Florin Matache Duna A61 Therapeutic options in a case of severe psoriasis associated with both HIV infection and hepatitis C virus previously treated with fumaric acid esters Rodica Olteanu, Roxana Ion, Alexandra Zota, Isra Ennour Jaballah, Lara Mahfoud, Georgeta Preda, Magda Constantin A62 Prevalence of autoantibodies against gangliosides in asymptomatic HIV-infected patients Ilinca Nicolae, Corina Daniela Ene, Mădălina Irina Mitran, Vasile Benea, Mircea Tampa, Simona Roxana Georgescu A63 Subclinical inflammation in HIV-infected patients undergoing antiretroviral therapy – a cross sectional study Iulia Cristina Bodoșca, Cristina Murariu, Cătălin Tilișcan, Victoria Aramă, Cristina Popescu, Daniela Munteanu, Mihaela Rădulescu, Violeta Molagic, Raluca Năstase, Alina Orfanu, Anca Leuștean, Remulus Catană, Anca Negru, Adrian Streinu-Cercel, Sorin Aramă A64 Severe Guillain-Barré syndrome occurring after chickenpox with favorable evolution Iuliana CAramăngiu, Ovidiu Rosca, Monica Cialma, Radu Opreanu, Laurențiu Vochita, Iosif Marincu A65 Echovirus 30 infection with pulmonary and cardiac complications – case report Vlad Murărescu, Marilena Palaghiță, Alina Cristina Neguț, Cornel Camburu, Adrian Streinu-Cercel A66 Herpetic encephalitis with favorable evolution in an adult immunocompetent patient Irina Duşan, Patricia Poptelecan, Bogdan Trincă, Sorina Mitrescu, Livius Tirnea, Iosif Marincu A67 Clinical-evolutional aspects in present-day measles Narcisa Nicolescu, Alexandru Crișan, Voichița Lăzureanu, Ruxandra Laza, Virgil Musta, Adelina-Raluca Marinescu, Andreea Bîrlad A68 Pneumococcal superinfection in children with influenza Victor Daniel Miron, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Daniela Pițigoi, Oana Săndulescu, Monica Luminița Luminos A69 Varicella complicated with transverse myelitis - case presentation Monica Luminos, Endis Osman, Magdalena Vasile, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Camelia Kouris, Sabina Șchiopu, Mădălina Merișescu A70 Clinical forms of enterovirus infections during the summer season of 2016 Monica Luminos, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Camelia Kouris, Endis Osman, Sabina Vintilă, Magda Vasile, Mădălina Merișescu A71 Face off – HIV and lymphoma – case series presentation Liana Cătălina Gavriliu, Otilia Elisabeta Benea, Alina Angelescu, Ramona Zamfir, Daniela Camburu, Georgeta Ducu, Alina Cozma, Roxana Dumitriu, Manuela Podani, Șerban Benea, Mihaela Ionică A72 Coxsackie infection complicated by pancytopenia – pediatric case report Gheorghiță Jugulete, Adina Stăncescu, Cristina Elena Popescu, Luminița Marin, Diana Zaharia, Cristina Dumitrescu, Lucia Tudor, Sabina Vintilă A73 Viral respiratory infections in children in the season 2015–2016 Constanța-Angelica Vișan, Anca Cristina Drăgănescu, Anuța Bilașco, Magda Vasile, Mădălina Merișescu, Camelia Kouris, Cristina Negulescu, Endis Osman, Diana-Maria Slavu, Sabina Vintilă, Daniela Pițigoi, Monica Luminos A75 The severity of A H1N1 Influenza infection in the 2015–2016 season Cleo Roșculeț, Catrinel Olimpia Ciuca, Dalila Toma, Cătălin Apostolescu, Andrei Rogoz, Andrei Stangaciu, Viorica Mitescu, Doina Iovănescu, Cornel Camburu, Bogdana Manu A76 Acute respiratory distress syndrome in a child with measles Ana Vaduva-Enoiu, Ramona Georgiana Stanculete, Adelina Raluca Marinescu, Voichita Elena Lazureanu A77 Management challenges of right-sided infectious endocarditis in an HIV positive patient – case presentation Elena-Violeta Niță, Sînziana Dumitru, Daniela-Ioana Munteanu, Anca Ruxandra Negru, Remulus Catană, Ioan Diaconu, Bogdana Manu, Ligia Ionescu, Liliana Ion, Cătălin Tilișcan, Victoria Aramă A78 Bacterial infection in critical patients with severe A H1N1 influenza virus infection (epidemiology, development, therapeutic decisions) Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz, Cătălin Apostolescu, Viorica Mitescu, Tudor Vladoiu, Dalila Toma, Catrinel Ciuca A79 Epidemiological aspects of severe acute respiratory infection cases (SARI) in the season 2015–2016, in the Clinical Hospital of Infectious Diseases – Constanța, Romania Iulia Gabriela Șerban, Marioara Neacșu A80Overexpression of IL-6 trans signaling pathway in viral infections Simona Roxana Georgescu, Vasile Benea, Corina Daniela Ene, Mircea Tampa, Cristina Iulia Mitran, Ilinca Nicolae A81 Acute viral hepatitis B with persistent HBsAg – description and evolution George Ciprian Pribac, Mirandolina Prisca, Fulvia Ursoiu, Carmen Neamtu, Bogdan Totolici, Coralia Cotoraci, Aurel Ardelean A82 Prevalence of cervical pathogens in a population of pregnant female patients monitored in a tertiary care hospital in Bucharest, Romania Simona Elena Albu, Mara Carsote, Beatrice Miclăuș, Diana Mihai, Oana Săndulescu, Cristina Vasiliu A83 Prevalence of group B Streptococcus during pregnancy in a cohort of patients monitored in a tertiary care hospital in Bucharest, Romania Cristina Vasiliu, Mara Carsote, Corina Gorgoi, Beatrice Miclăuș, Diana Mihai, Oana Săndulescu, Simona Elena Albu A84 Infectious hematoma in the gastrocnemius muscle – case presentation Amelia Blescun, Gelu Breaza A85 Reflections towards the underexplored HTLV Romanian viral circulation - adult T‐cell leukemia/lymphomas, a case series Sabina Vintila, Felicia Mihai, Meilin Omer, Cornel Dragan, Daniela Pitigoi A86 A febrile confusion syndrome with acute onset – case presentation Mirela Ciucu, Marius-Dan Ionescu, Cristina Roskanovic, Valentina Barbu, Iulian Diaconescu, Florentina Dumitrescu, Irina Niculescu A87 Retrobulbar optic neuritis in a HIV-positive patient - case report Mihaela Ionică, Ramona-Alexandra Zamfir, Alina Cozma, Otilia Elisabeta Benea A88 A rare presentation of Q fever – case presentation Alexandra-Sînziana Dumitru, Daniela-Ioana Munteanu, Violeta Niță, Cristina Popescu, Iulia Bodosca, Angelica Tenita, Viorica Ispas, Victoria Aramă A89 Tinea incognita – case presentation Vasile Benea, Simona Roxana Georgescu, Mircea Tampa, Diana Oana Leahu, Cristina Maria Safta, Mihaela Anca Benea A90 Incidence and risk factors associated with TORCH infections during pregnancy Oana Săndulescu, Octavian Munteanu, Roxana Bohâlțea, Livia Trașcă, Monica Cîrstoiu A91 Acute respiratory failure in critical patients with sepsis Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz, Cătălin Gabriel Apostolescu, Viorica Daniela Mitescu, Tudor Gheorghe Vladoiu, Dalila Toma, Catrinel Ciuca A92 Cochleo-vestibular deficit secondary to Granulicatella elegans meningitis Mădălina Georgescu A93 Influenza 2015/2016 – clinical, epidemiological and virological characteristics of cases admitted in three infectious diseases hospitals Daniela Pițigoi, Alina Elena Ivanciuc, Mihaela Lazar, Teodora Ionescu, Carmen Maria Cherciu, Cristina Țecu, Maria Elena Mihai, Maria Nițescu, Rodica Bacruban, Delia Azamfire, Aura Dumitrescu, Elena Ianosik, Daniela Leca, Elena Duca, Andra Teodor, Codrina Bejan, Emanoil Ceaușu, Simin-Aysel Florescu, Corneliu Popescu, Grațiela Târdei, Codrina Juganariu, Emilia Lupulescu A94 Severe complications of varicella requiring hospitalization in previously healthy children in Brașov county Ligia Rodina, Maria Elena Cocuz A95 Clinical forms of Clostridium difficile colitis in children Gheorghiță Jugulete, Adina Stăncescu, Cristina Elena Popescu, Luminița Marin, Diana Zaharia, Cristina Dumitrescu, Endis Osman A96 Community-acquired pneumonia – demographic, clinical and etiological aspects Irina Niculescu, Augustin Cupșa, Iulian Diaconescu, Florentina Dumitrescu, Livia Dragonu, Andreea Stoian, Lucian Giubelan, Cristina Roskanovic A97 Acute myocarditis in an adult patient with chickenpox - Case report Ramona-Alexandra Zamfir, Mihaela Ionica, Otilia-Elisabeta Benea A98 Caustic oropharyngeal wound with acute group F streptococcal superinfection mimicking diphtheria – case report and differential diagnosis Maria-Cristina Sîrbu, AnaMaria Dobrotă, Alina Cristina Neguț, Roxana Duda, Rodica Bacruban, Daniela Pițigoi, Cristiana Cerasella Dragomirescu, Daniela Tălăpan, Olga Dorobăț, Adrian Streinu-Cercel, Anca Streinu-Cercel A99 Clostridium difficile infection in HIV-positive patients admitted in the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” in 2015 Mihaela Ionica, Ramona-Alexandra Zamfir, Alina Cozma, Otilia Elisabeta Benea A100 Title: Epidemiology of Candida oral infections (stomatitis) in Romania Sergiu Fendrihan, Ecaterina Scortan, Mircea Ioan Popa A101 Anthrax case series in south-eastern Romania Corneliu P Popescu, Șerban N Benea, Andra E Petcu, Adriana Hristea, Adrian Abagiu, Iuliana A Podea, Raluca E Jipa, Georgeta Ducu, Raluca M Hrișcă, Dragoș Florea, Manuela Nica, Eliza Manea, Simona Merișor, Cristian M Nicolae, Simin A Florescu, Irina M Dumitru, Emanoil Ceaușu, Sorin Rugină, Ruxandra V Moroti A102 Knowledge, risk perception and attitudes of healthcare workers at the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” regarding Ebola Daniela Pițigoi, Teodora Ionescu, Oana Săndulescu, Maria Nițescu, Bogdan Nițescu, Iulia Monica Mustaţă, Sorina Claudia Boldeanu, Florentina Furtunescu, Adrian Streinu-Cercel A103 A case of abdominopelvic actinomycosis with successful short-term antibiotic treatment Diana Gabriela Iacob, Simona Alexandra Iacob, Mihaela Gheorghe A104 A case of pneumonia caused by Raoultella planticola Iulian Diaconescu, Irina Niculescu, Floretina Dumitrescu, Lucian Giubelan A105 Vitamin D deficiency and sepsis in childhood Adriana Slavcovici, Raluca Tripon, Roxana Iubu, Cristian Marcu, Mihaela Sabou, Monica Muntean A106 The clinical and epidemiological aspects and prophylaxis of Lyme disease among patients who presented with tick bites to the Clinical Infectious Disease Hospital “Toma Ciorbă” Ion Chiriac, Tiberiu Holban, Liviu Tazlavanu A107 Drug-resistant tuberculosis in HIV infected patients Raluca Jipa, Eliza Manea, Roxana Cernat, Kezdi Iringo, Andrei Vâță, Manuela Arbune, Teodora Moisil, Adriana Hristea A108 Kidney injury molecule-1 and urinary tract infections Corina-Daniela Ene, Ilinca Nicolae, Roxana Simona Georgescu A109 The impact of microbiological agents on serum gangliosides in patients with benign prostate hyperplasia Corina-Daniela Ene, Cosmin-Victor Ene, Roxana Simona Georgescu, Marilena Ciortea , Lucreția Dulgheru, Ilinca Nicolae A110 Toxocariasis - the experience of the Iași Infectious Diseases Hospital between 2013–2015 Mihaela Cătălina Luca, Ioana-Alina Harja-Alexa, Roxana Nemescu, Mădălina Popazu, Andrei Ștefan Luca A111 Species of anaerobic Gram-positive cocci involved in odontogenic abscesses Gabriela Bancescu, Bogdan Dabu, Adrian Bancescu A112 Clostridium difficile infection recurrences Eliza Manea, Raluca Jipa, Adriana Hristea A113 Differential diagnosis of staphylococcal and tuberculous osteodiscitis – case report Adina Elena Ilie, Săftica-Mariana Pohrib, Alina Cristina Neguț, Maria-Sabina Tache, Maria Magdalena Moțoi, Oana Săndulescu, Ion Aurel Iliescu, Adrian Streinu-Cercel A114 Severe clinical forms of respiratory syncytial virus infections Cristina Tecu, Maria-Elena Mihai, Mihaela Lazăr, Carmen Cherciu, Alina Ivanciuc, Daniela Pițigoi, Emilia Lupulescu A115 Acinetobacter baumannii postoperative sepsis associated with Clostridium difficile enterocolitis in an immune suppressed elderly patient Mirela Paliu, Manuela Curescu, Bianca Cerbu, Iosif Marincu A116 Risk factors and their impact on psychopathology and quality of life among people living with HIV/AIDS in Romania Fulvia Ursoiu, Mirandolina Prișcă, George Ciprian Pribac A117 Antivirals susceptibility of influenza viruses circulating in Romania Maria Elena Mihai, Carmen Maria Cherciu, Alina Elena Ivanciuc, Cristina Tecu, Emilia Lupulescu A118 Retrospective study of hospitalized cases of sepsis at the Hospital Clinic of Infectious Diseases “Toma Ciorbă” Irina Bunescu, Tiberiu Holban, Ana Pasnin, Stela Semeniuc, Raisa Popovici, Galina Chiriacov",2016 Nov 1,"['Niculae, Cristian-Mihail', 'Manea, Eliza', 'Jipa, Raluca', 'Merisor, Simona', 'Moroti, Ruxandra', 'Benea, Serban', 'Hristea, Adriana', 'Neguț, Alina Cristina', 'Săndulescu, Oana', 'Streinu-Cercel, Anca', 'Mărculescu, Dana', 'Andrei, Magdalena Lorena', 'Ilie, Veronica', 'Popa, Marcela', 'Bleotu, Coralia', 'Chifiriuc, Carmen', 'Popa, Mircea Ioan', 'Streinu-Cercel, Adrian', 'Orfanu, Alina', 'Popescu, Cristina', 'Leuștean, Anca', 'Catană, Remulus', 'Negru, Anca', 'Badea, Alexandra', 'Orfanu, Radu', 'Tilișcan, Cătălin', 'Aramă, Victoria', 'Aramă, Ştefan Sorin', 'Vișan, Constanța-Angelica', 'Drăgănescu, Anca-Cristina', 'Bilașco, Anuța', 'Kouris, Camelia', 'Merișescu, Mădălina', 'Vasile, Magdalena', 'Slavu, Diana-Maria', 'Vintilă, Sabina', 'Osman, Endis', 'Oprea, Alina', 'Sandu, Sabina', 'Luminos, Monica', 'Orfanu, Alina', 'Aramă, Victoria', 'Aramă, Ştefan Sorin', 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'Dragomirescu, Cristina', 'Leuștean, Anca', 'Murariu, Cristina', 'Stratan, Laurențiu', 'Badea, Alexandra', 'Catană, Remulus', 'Orfanu, Alina', 'Năstase, Raluca Mihaela', 'Molagic, Violeta', 'Munteanu, Daniela', 'Tilișcan, Cătălin', 'Aramă, Victoria', 'Aramă, Victoria', 'Catană, Remulus', 'Dragomirescu, Cristina', 'Murariu, Cristina', 'Leuștean, Anca', 'Stratan, Laurențiu', 'Badea, Alexandra', 'Orfanu, Alina', 'Negru, Anca', 'Năstase, Raluca', 'Molagic, Violeta', 'Munteanu, Daniela', 'Tilișcan, Cătălin', 'Rădulescu, Mihaela', 'Diaconu, Ioan', 'Niță, Violeta', 'Bodoșca, Iulia', 'Popescu, Cristina', 'Popescu, Cristina', 'Badea, Alexandra', 'Leuștean, Anca', 'Orfanu, Alina', 'Negru, Anca', 'Stratan, Laurențiu', 'Dragomirescu, Cristina', 'Catană, Remulus', 'Murariu, Cristina', 'Molagic, Violeta', 'Năstase, Raluca', 'Tilișcan, Cătălin', 'Munteanu, Daniela', 'Rădulescu, Mihaela', 'Diaconu, Ioan', 'Niță, Violeta', 'Bodoșca, Iulia', 'Aramă, Victoria', 'Popescu, Cristina', 'Orfanu, Alina', 'Leuștean, Anca', 'Badea, Alexandra', 'Stratan, Laurențiu', 'Catană, Remulus', 'Tilișcan, Cătălin', 'Aramă, Victoria', 'Popescu, Cristina', 'Murariu, Cristina', 'Dragomirescu, Cristina', 'Leuștean, Anca', 'Stratan, Laurențiu', 'Orfanu, Alina', 'Badea, Alexandra', 'Catană, Remulus', 'Negru, Anca', 'Tilișcan, Cătălin', 'Munteanu, Daniela', 'Rădulescu, Mihaela', 'Molagic, Violeta', 'Năstase, Raluca Mihaela', 'Diaconu, Ioan Alexandru', 'Bodoșca, Iulia', 'Niță, Violeta', 'Aramă, Victoria', 'Erturk, Yagmur', 'Săndulescu, Oana', 'Neguț, Alina Cristina', 'Șchiopu, Claudiu Mihai', 'Streinu-Cercel, Adrian', 'Streinu-Cercel, Anca', 'Molagic, Violeta', 'Tilișcan, Cătălin', 'Popescu, Cristina', 'Mihăilescu, Raluca', 'Munteanu, Daniela', 'Năstase, Raluca', 'Negru, Anca', 'Tenita, Angelica', 'Aramă, Victoria', 'Aramă, Ștefan Sorin', 'Iacob, Simona Alexandra', 'Iacob, Diana Gabriela', 'Luminos, Monica', 'Streinu-Cercel, Anca', 'Săndulescu, Oana', 'Predescu, Mioara', 'Mărdărescu, Alexandra', 'Tilișcan, Cătălin', 'Săndulescu, Mihai', 'Șchiopu, Claudiu Mihai', 'Streinu-Cercel, Adrian', 'Roșculeț, Cleo Nicoleta', 'Ciuca, Catrinel Olimpia', 'Toma, Dalila Ana', 'Apostolescu, Cătălin Gabriel', 'Rogoz, Andrei', 'Mitu, Cristina Elena', 'Stangaciu, Andrei', 'Mitescu, Viorica Daniela', 'Vladoiu, Tudor Gheorghe', 'Iovănescu, Doina Viorica', 'Săndulescu, Oana', 'Streinu-Cercel, Anca', 'Stoica, Monica Andreea', 'Preoțescu, Liliana Lucia', 'Manolache, Daniela', 'Ceapraga, Gabriela Jana', 'Moțoi, Maria Magdalena', 'Bradu, Luminița', 'Ilie, Adina', 'Mircea, Gabriela', 'Durbală, Ionel', 'Streinu-Cercel, Adrian', 'Russu, Irina', 'Holban, Tiberiu', 'Pantilimonov, Tatiana', 'Chiriacov, Galina', 'Macvovei, Arcadie', 'Scorohodico, Elena', 'Dmitriev, Oleg', 'Costache, Diana Alexandra', 'Benea, Anca', 'Manea, Eliza', 'Niculae, Cristian', 'Jipa, Raluca', 'Hristea, Adriana', 'Benea, Elisabeta', 'Moroti, Ruxandra', 'Benea, Șerban', 'Mitran, Mihai', 'Georgescu, Carmen', 'Mitran, Loredana', 'Vladareanu, Simona', 'Magirescu, Andreea Ioana', 'Andreev, Viorica', 'Nicolau, Cristina', 'Largu, Alexandra', 'Dorobat, Carmen', 'Manciuc, Carmen', 'Andreev, Viorica', 'Magirescu, Andreea Ioana', 'Isac, Ina', 'Nicolau, Cristina', 'Largu, Alexandra', 'Dorobat, Carmen', 'Manciuc, Carmen', 'Șerban, Iulia Gabriela', 'Resul, Ghiulendan', 'Marcaș, Consuela', 'Marincu, Iosif', 'Poptelecan, Patricia', 'Trincă, Bogdan', 'Mitrescu, Sorina', 'Tudor, Anca', 'Vlad, Daliborca', 'Tirnea, Livius', 'Baydaroglu, Nurcan', 'Neguț, Alina Cristina', 'Săndulescu, Oana', 'Manolache, Daniela', 'Ceapraga, Gabriela', 'Stoica, Monica Andreea', 'Streinu-Cercel, Anca', 'Streinu-Cercel, Adrian', 'Manciuc, Carmen', 'Pagute, Mariana', 'Nicolau, Cristina', 'Dorobăț, Carmen', 'Largu, Alexandra', 'Diaconu, Ioan-Alexandru', 'Stratan, Laurențiu', 'Ion, Daniela', 'Nichita, Luciana', 'Popescu, Cristina', 'Năstase, Raluca', 'Munteanu, Daniela', 'Molagic, Violeta', 'Tilișcan, Cătălin', 'Rădulescu, Mihaela', 'Diaconu, Alexandra', 'Negru, Anca', 'Orfanu, Alina', 'Dragomirescu, Cristina', 'Catană, Remulus', 'Leuștean, Anca', 'Duport-Dodot, Irina', 'Murariu, Cristina', 'Bodoșca, Iulia', 'Niță, Violeta', 'Badea, Alexandra', 'Aramă, Victoria', 'Mărdărescu, Mariana', 'Petre, Cristina', 'Iancu, Marieta', 'Ungurianu, Rodica', 'Cibea, Alina', 'Drăghicenoiu, Ruxandra', 'Tudor, Ana Maria', 'Vlad, Delia', 'Petrea, Sorin', 'Matei, Carina', 'Oțelea, Dan', 'Crăciun, Carmen', 'Anghelina, Cristian', 'Mărdărescu, Alexandra', 'Dumea, Elena', 'Streinu-Cercel, Adrian', 'Rugină, Sorin', 'Petcu, Lucian Cristian', 'Halichidis, Stela', 'Cambrea, Simona Claudia', 'Chiriac, Carmen', 'Bodnar, Nina-Ioana', 'Zaharia-Kezdi, Iringo-Erzsebet', 'Gîrbovan, Cristina', 'Incze, Andrea', 'Georgescu, Anca Meda', 'Iacob, Simona Alexandra', 'Iacob, Diana Gabriela', 'Panaitescu, Eugenia', 'Luminos, Monica', 'Cojocaru, Manole', 'Iacob, Simona Alexandra', 'Iacob, Diana Gabriela', 'Luminos, Monica', 'Laurențiu, Vochita', 'Andreia, Vochita', 'Radu, Opreanu', 'Bogdan, Trinca', 'Ovidiu, Rosca', 'Iosif, Marincu', 'Zamfir, Ramona', 'Angelescu, Alina', 'Popa, Alena Andreea', 'Jipa, Raluca', 'Moroti, Ruxandra', 'Hristea, Adriana', 'Gavriliu, Liana', 'Benea, Șerban', 'Benea, Elisabeta', 'Popa, Alena-Andreea', 'Ducu, Georgeta', 'Camburu, Daniela', 'Cozma, Alina', 'Podani, Manuela', 'Dumitriu, Roxana', 'Gavriliu, Liana', 'Benea, Șerban', 'Benea, Elisabeta', 'Stoian, Andreea Cristina', 'Dumitrescu, Florentina', 'Cupșa, Augustin', 'Giubelan, Lucian', 'Niculescu, Irina', 'Ionescu, Loredana', 'Dragonu, Livia', 'Abagiu, Adrian Octavian', 'Stoica, Loredana Nicoleta', 'Blaga, Catrinel', 'Koulosousas, Archontis', 'Ștefănescu, Roxana', 'Atomoaie, Alice', 'Paraschiv, Florentina', 'Duna, Florin Matache', 'Olteanu, Rodica', 'Ion, Roxana', 'Zota, Alexandra', 'Jaballah, Isra Ennour', 'Mahfoud, Lara', 'Preda, Georgeta', 'Constantin, Magda', 'Nicolae, Ilinca', 'Ene, Corina Daniela', 'Mitran, Mădălina Irina', 'Benea, Vasile', 'Tampa, Mircea', 'Georgescu, Simona Roxana', 'Bodoșca, Iulia Cristina', 'Murariu, Cristina', 'Tilișcan, Cătălin', 'Aramă, Victoria', 'Popescu, Cristina', 'Munteanu, Daniela', 'Rădulescu, Mihaela', 'Molagic, Violeta', 'Năstase, Raluca', 'Orfanu, Alina', 'Leuștean, Anca', 'Catană, Remulus', 'Negru, Anca', 'Streinu-Cercel, Adrian', 'Aramă, Sorin', 'Caramăngiu, Iuliana', 'Rosca, Ovidiu', 'Cialma, Monica', 'Opreanu, Radu', 'Vochita, Laurențiu', 'Marincu, Iosif', 'Murărescu, Vlad', 'Palaghiță, Marilena', 'Neguț, Alina Cristina', 'Camburu, Cornel', 'Streinu-Cercel, Adrian', 'Duşan, Irina', 'Poptelecan, Patricia', 'Trincă, Bogdan', 'Mitrescu, Sorina', 'Tirnea, Livius', 'Marincu, Iosif', 'Nicolescu, Narcisa', 'Crișan, Alexandru', 'Lăzureanu, Voichița', 'Laza, Ruxandra', 'Musta, Virgil', 'Marinescu, Adelina-Raluca', 'Bîrlad, Andreea', 'Miron, Victor Daniel', 'Drăgănescu, Anca Cristina', 'Vișan, Constanța-Angelica', 'Bilașco, Anuța', 'Pițigoi, Daniela', 'Săndulescu, Oana', 'Luminos, Monica Luminița', 'Luminos, Monica', 'Osman, Endis', 'Vasile, Magdalena', 'Drăgănescu, Anca Cristina', 'Vișan, Constanța-Angelica', 'Bilașco, Anuța', 'Kouris, Camelia', 'Șchiopu, Sabina', 'Merișescu, Mădălina', 'Luminos, Monica', 'Drăgănescu, Anca Cristina', 'Vișan, Constanța-Angelica', 'Bilașco, Anuța', 'Kouris, Camelia', 'Osman, Endis', 'Vintilă, Sabina', 'Vasile, Magda', 'Merișescu, Mădălina', 'Gavriliu, Liana Cătălina', 'Benea, Otilia Elisabeta', 'Angelescu, Alina', 'Zamfir, Ramona', 'Camburu, Daniela', 'Ducu, Georgeta', 'Cozma, Alina', 'Dumitriu, Roxana', 'Podani, Manuela', 'Benea, Șerban', 'Ionică, Mihaela', 'Jugulete, Gheorghiță', 'Stăncescu, Adina', 'Popescu, Cristina Elena', 'Marin, Luminița', 'Zaharia, Diana', 'Dumitrescu, Cristina', 'Tudor, Lucia', 'Vintilă, Sabina', 'Vișan, Constanța-Angelica', 'Drăgănescu, Anca Cristina', 'Bilașco, Anuța', 'Vasile, Magda', 'Merișescu, Mădălina', 'Kouris, Camelia', 'Negulescu, Cristina', 'Osman, Endis', 'Slavu, Diana-Maria', 'Vintilă, Sabina', 'Pițigoi, Daniela', 'Luminos, Monica', 'Caliman-Sturdza, Olga Adriana', 'Roșculeț, Cleo', 'Ciuca, Catrinel Olimpia', 'Toma, Dalila', 'Apostolescu, Cătălin', 'Rogoz, Andrei', 'Stangaciu, Andrei', 'Mitescu, Viorica', 'Iovănescu, Doina', 'Camburu, Cornel', 'Manu, Bogdana', 'Vaduva-Enoiu, Ana', 'Stanculete, Ramona Georgiana', 'Marinescu, Adelina Raluca', 'Lazureanu, Voichita Elena', 'Niță, Elena-Violeta', 'Dumitru, Sînziana', 'Munteanu, Daniela-Ioana', 'Negru, Anca Ruxandra', 'Catană, Remulus', 'Diaconu, Ioan', 'Manu, Bogdana', 'Ionescu, Ligia', 'Ion, Liliana', 'Tilișcan, Cătălin', 'Aramă, Victoria', 'Iovănescu, Doina Viorica', 'Roșculeț, Cleo Nicoleta', 'Rogoz, Andrei', 'Apostolescu, Cătălin', 'Mitescu, Viorica', 'Vladoiu, Tudor', 'Toma, Dalila', 'Ciuca, Catrinel', 'Șerban, Iulia Gabriela', 'Neacșu, Marioara', 'Georgescu, Simona Roxana', 'Benea, Vasile', 'Ene, Corina Daniela', 'Tampa, Mircea', 'Mitran, Cristina Iulia', 'Nicolae, Ilinca', 'Pribac, George Ciprian', 'Prisca, Mirandolina', 'Ursoiu, Fulvia', 'Neamtu, Carmen', 'Totolici, Bogdan', 'Cotoraci, Coralia', 'Ardelean, Aurel', 'Albu, Simona Elena', 'Carsote, Mara', 'Miclăuș, Beatrice', 'Mihai, Diana', 'Săndulescu, Oana', 'Vasiliu, Cristina', 'Vasiliu, Cristina', 'Carsote, Mara', 'Gorgoi, Corina', 'Miclăuș, Beatrice', 'Mihai, Diana', 'Săndulescu, Oana', 'Albu, Simona Elena', 'Blescun, Amelia', 'Breaza, Gelu', 'Vintila, Sabina', 'Mihai, Felicia', 'Omer, Meilin', 'Dragan, Cornel', 'Pitigoi, Daniela', 'Ciucu, Mirela', 'Ionescu, Marius-Dan', 'Roskanovic, Cristina', 'Barbu, Valentina', 'Diaconescu, Iulian', 'Dumitrescu, Florentina', 'Niculescu, Irina', 'Ionică, Mihaela', 'Zamfir, Ramona-Alexandra', 'Cozma, Alina', 'Benea, Otilia Elisabeta', 'Dumitru, Alexandra-Sînziana', 'Munteanu, Daniela-Ioana', 'Niță, Violeta', 'Popescu, Cristina', 'Bodosca, Iulia', 'Tenita, Angelica', 'Ispas, Viorica', 'Aramă, Victoria', 'Benea, Vasile', 'Georgescu, Simona Roxana', 'Tampa, Mircea', 'Leahu, Diana Oana', 'Safta, Cristina Maria', 'Benea, Mihaela Anca', 'Săndulescu, Oana', 'Munteanu, Octavian', 'Bohâlțea, Roxana', 'Trașcă, Livia', 'Cîrstoiu, Monica', 'Iovănescu, Doina Viorica', 'Roșculeț, Cleo Nicoleta', 'Rogoz, Andrei', 'Apostolescu, Cătălin Gabriel', 'Mitescu, Viorica Daniela', 'Vladoiu, Tudor Gheorghe', 'Toma, Dalila', 'Ciuca, Catrinel', 'Georgescu, Mădălina', 'Pițigoi, Daniela', 'Ivanciuc, Alina Elena', 'Lazar, Mihaela', 'Ionescu, Teodora', 'Cherciu, Carmen Maria', 'Țecu, Cristina', 'Mihai, Maria Elena', 'Nițescu, Maria', 'Bacruban, Rodica', 'Azamfire, Delia', 'Dumitrescu, Aura', 'Ianosik, Elena', 'Leca, Daniela', 'Duca, Elena', 'Teodor, Andra', 'Bejan, Codrina', 'Ceaușu, Emanoil', 'Florescu, Simin-Aysel', 'Popescu, Corneliu', 'Târdei, Grațiela', 'Juganariu, Codrina', 'Lupulescu, Emilia', 'Rodina, Ligia', 'Cocuz, Maria Elena', 'Jugulete, Gheorghiță', 'Stăncescu, Adina', 'Popescu, Cristina Elena', 'Marin, Luminița', 'Zaharia, Diana', 'Dumitrescu, Cristina', 'Osman, Endis', 'Niculescu, Irina', 'Cupșa, Augustin', 'Diaconescu, Iulian', 'Dumitrescu, Florentina', 'Dragonu, Livia', 'Stoian, Andreea', 'Giubelan, Lucian', 'Roskanovic, Cristina', 'Zamfir, Ramona-Alexandra', 'Ionica, Mihaela', 'Benea, Otilia-Elisabeta', 'Sîrbu, Maria-Cristina', 'Dobrotă, AnaMaria', 'Neguț, Alina Cristina', 'Duda, Roxana', 'Bacruban, Rodica', 'Pițigoi, Daniela', 'Dragomirescu, Cristiana Cerasella', 'Tălăpan, Daniela', 'Dorobăț, Olga', 'Streinu-Cercel, Adrian', 'Streinu-Cercel, Anca', 'Ionica, Mihaela', 'Zamfir, Ramona-Alexandra', 'Cozma, Alina', 'Benea, Otilia Elisabeta', 'Fendrihan, Sergiu', 'Scortan, Ecaterina', 'Popa, Mircea Ioan', 'Popescu, Corneliu P.', 'Benea, Șerban N.', 'Petcu, Andra E.', 'Hristea, Adriana', 'Abagiu, Adrian', 'Podea, Iuliana A.', 'Jipa, Raluca E.', 'Ducu, Georgeta', 'Hrișcă, Raluca M.', 'Florea, Dragoș', 'Nica, Manuela', 'Manea, Eliza', 'Merișor, Simona', 'Nicolae, Cristian M.', 'Florescu, Simin A.', 'Dumitru, Irina M.', 'Ceaușu, Emanoil', 'Rugină, Sorin', 'Moroti, Ruxandra V.', 'Pițigoi, Daniela', 'Ionescu, Teodora', 'Săndulescu, Oana', 'Nițescu, Maria', 'Nițescu, Bogdan', 'Mustaţă, Iulia Monica', 'Boldeanu, Sorina Claudia', 'Furtunescu, Florentina', 'Streinu-Cercel, Adrian', 'Iacob, Diana Gabriela', 'Iacob, Simona Alexandra', 'Gheorghe, Mihaela', 'Slavcovici, Adriana', 'Tripon, Raluca', 'Iubu, Roxana', 'Marcu, Cristian', 'Sabou, Mihaela', 'Muntean, Monica', 'Chiriac, Ion', 'Holban, Tiberiu', 'Tazlavanu, Liviu', 'Jipa, Raluca', 'Manea, Eliza', 'Cernat, Roxana', 'Iringo, Kezdi', 'Vâță, Andrei', 'Arbune, Manuela', 'Moisil, Teodora', 'Hristea, Adriana', 'Ene, Corina-Daniela', 'Nicolae, Ilinca', 'Georgescu, Roxana Simona', 'Ene, Corina-Daniela', 'Ene, Cosmin-Victor', 'Georgescu, Roxana Simona', 'Ciortea, Marilena', 'Dulgheru, Lucreția', 'Nicolae, Ilinca', 'Luca, Mihaela Cătălina', 'Harja-Alexa, Ioana-Alina', 'Nemescu, Roxana', 'Popazu, Mădălina', 'Luca, Andrei Ștefan', 'Bancescu, Gabriela', 'Dabu, Bogdan', 'Bancescu, Adrian', 'Manea, Eliza', 'Jipa, Raluca', 'Hristea, Adriana', 'Ilie, Adina Elena', 'Pohrib, Săftica-Mariana', 'Neguț, Alina Cristina', 'Tache, Maria-Sabina', 'Moțoi, Maria Magdalena', 'Săndulescu, Oana', 'Iliescu, Ion Aurel', 'Streinu-Cercel, Adrian', 'Tecu, Cristina', 'Mihai, Maria-Elena', 'Lazăr, Mihaela', 'Cherciu, Carmen', 'Ivanciuc, Alina', 'Pițigoi, Daniela', 'Lupulescu, Emilia', 'Paliu, Mirela', 'Curescu, Manuela', 'Cerbu, Bianca', 'Marincu, Iosif', 'Mihai, Maria Elena', 'Cherciu, Carmen Maria', 'Ivanciuc, Alina Elena', 'Tecu, Cristina', 'Lupulescu, Emilia', 'Bunescu, Irina', 'Holban, Tiberiu', 'Pasnin, Ana', 'Semeniuc, Stela', 'Popovici, Raisa', 'Chiriacov, Galina']",BMC Infect Dis,,,True
a09daa4101801d9b65bcc053116505b0022e0640,PMC,Planning horizon affects prophylactic decision-making and epidemic dynamics,http://dx.doi.org/10.7717/peerj.2678,PMC5103819,27843714,CC BY,"The spread of infectious diseases can be impacted by human behavior, and behavioral decisions often depend implicitly on a planning horizon—the time in the future over which options are weighed. We investigate the effects of planning horizons on epidemic dynamics. We developed an epidemiological agent-based model (along with an ODE analog) to explore the decision-making of self-interested individuals on adopting prophylactic behavior. The decision-making process incorporates prophylaxis efficacy and disease prevalence with the individuals’ payoffs and planning horizon. Our results show that for short and long planning horizons individuals do not consider engaging in prophylactic behavior. In contrast, individuals adopt prophylactic behavior when considering intermediate planning horizons. Such adoption, however, is not always monotonically associated with the prevalence of the disease, depending on the perceived protection efficacy and the disease parameters. Adoption of prophylactic behavior reduces the epidemic peak size while prolonging the epidemic and potentially generates secondary waves of infection. These effects can be made stronger by increasing the behavioral decision frequency or distorting an individual’s perceived risk of infection.",2016 Nov 8,"['Nardin, Luis G.', 'Miller, Craig R.', 'Ridenhour, Benjamin J.', 'Krone, Stephen M.', 'Joyce, Paul', 'Baumgaertner, Bert O.']",PeerJ,,,False
352fc70d79c0668a5a7583538fe0167c1fd785d1,PMC,Bats and Academics: How Do Scientists Perceive Their Object of Study?,http://dx.doi.org/10.1371/journal.pone.0165969,PMC5104368,27832185,CC BY,"Bats are associated with conflicting perceptions among humans, ranging from affection to disgust. If these attitudes can be associated with various factors among the general public (e.g. social norms, lack of knowledge), it is also important to understand the attitude of scientists who study bats. Such reflexive information on the researchers community itself could indeed help designing adequate mixed communication tools aimed at protecting bats and their ecosystems, as well as humans living in their vicinity that could be exposed to their pathogens. Thus, we conducted an online survey targeting researchers who spend a part of their research activity studying bats. Our aim was to determine (1) how they perceive their object of study, (2) how they perceive the representation of bats in the media and by the general population, (3) how they protect themselves against pathogen infections during their research practices, and (4) their perceptions of the causes underlying the decline in bat populations worldwide. From the 587 completed responses (response rate of 28%) having a worldwide distribution, the heterogeneity of the scientists’ perception of their own object of study was highlighted. In the majority of cases, this depended on the type of research they conducted (i.e. laboratory versus field studies) as well as their research speciality. Our study revealed a high level of personal protection equipment being utilised against pathogens during scientific practices, although the role bats play as reservoirs for a number of emerging pathogens remains poorly known. Our results also disclosed the unanimity among specialists in attributing a direct role for humans in the global decline of bat populations, mainly via environmental change, deforestation, and agriculture intensification. Overall, the present study suggests the need for better communication regarding bats and their biology, their role within the scientific community, as well as in the general public population. As a consequence, increased knowledge regarding scientists’ perceptions of bats should improve the role scientists play in influencing the perception of bats by the general public.",2016 Nov 10,"['Boëte, Christophe', 'Morand, Serge']",PLoS One,,,True
add093424f4f1c1da746abb3227193fb2fefbefa,PMC,Viral Evasion Strategies in Type I IFN Signaling – A Summary of Recent Developments,http://dx.doi.org/10.3389/fimmu.2016.00498,PMC5104748,27891131,CC BY,"The immune system protects the organism against infections and the damage associated with them. The first line of defense against pathogens is the innate immune response. In the case of a viral infection, it induces the interferon (IFN) signaling cascade and eventually the expression of type I IFN, which then causes an antiviral state in the cells. However, many viruses have developed strategies to counteract this mechanism and prevent the production of IFN. In order to modulate or inhibit the IFN signaling cascade in their favor, viruses have found ways to interfere at every single step of the cascade, for example, by inducing protein degradation or cleavage, or by mediate protein polyubiquitination. In this article, we will review examples of viruses that modulate the IFN response and describe the mechanisms they use.",2016 Nov 11,"['Schulz, Katharina S.', 'Mossman, Karen L.']",Front Immunol,,,True
1146cc4ce6094ad35cc188166285b8c519986b6d,PMC,Complete Genome Sequences of Porcine Epidemic Diarrhea Virus Strains JSLS-1/2015 and JS-2/2015 Isolated from China,http://dx.doi.org/10.1128/genomeA.01200-16,PMC5105090,27834697,CC BY,"Two porcine epidemic diarrhea virus (PEDV) strains, JSLS-1/2015 and JS-2/2015, were isolated from piglets with watery diarrhea in South China. Two genomic sequences were highly homologous to the attenuated DR13 strain. Furthermore, JSLS-1/2015 contains a 24-amino-acid deletion in open reading frame 1b, which was first reported in PEDV isolates.",2016 Nov 10,"['Tao, Jie', 'Li, Benqiang', 'Zhang, Chunling', 'Liu, Huili']",Genome Announc,,,True
c36f5134f23a74677ed9d3a39f2eb8b4b19ad6e5,PMC,Complete Genome Sequence of Human Coronavirus OC43 Isolated from Mexico,http://dx.doi.org/10.1128/genomeA.01256-16,PMC5105101,27834708,CC BY,"We report the complete genome sequence of the first Mexican human coronavirus (HCoV) OC43, obtained by new-generation sequencing and a metagenomic approach, isolated from a child hospitalized with pneumonia. The genome is closely related to the other OC43 genome sequences available, ranging from 99.8% to 98.2% nucleotide sequence identity.",2016 Nov 10,"['Taboada, B. T.', 'Isa, P.', 'Espinoza, M. A.', 'Aponte, F. E.', 'Arias-Ortiz, M. A.', 'Monge-Martínez, J.', 'Rodríguez-Vázquez, R.', 'Díaz-Hernández, F.', 'Zárate-Vidal, F.', 'Wong-Chew, R. M.', 'Firo-Reyes, V.', 'del Río-Almendárez, C. N.', 'Gaitán-Meza, J.', 'Villaseñor-Sierra, A.', 'Martínez-Aguilar, G.', 'García-Borjas, M.', 'Noyola, D. E.', 'Pérez-Gónzalez, L. F.', 'López, S.', 'Santos-Preciado, J. I.', 'Arias, C. F.']",Genome Announc,,,True
2e313159ccde7f6fbd8d036a04beb2ce3a2809e4,PMC,Detection of a novel circovirus PCV3 in pigs with cardiac and multi-systemic inflammation,http://dx.doi.org/10.1186/s12985-016-0642-z,PMC5105309,27835942,CC BY,"BACKGROUND: Porcine circovirus 2 causes different clinical syndromes resulting in a significant economic loss in the pork industry. Three pigs with unexplained cardiac and multi-organ inflammation that tested negative for PCV2 and other known porcine pathogens were further analyzed. METHODS: Histology was used to identify microscopic lesions in multiple tissues. Metagenomics was used to detect viral sequences in tissue homogenates. In situ hybridization was used to detect viral RNA expression in cardiac tissue. RESULTS: In all three cases we characterized the genome of a new circovirus we called PCV3 with a replicase and capsid proteins showing 55 and 35 % identities to the genetically-closest proteins from a bat-feces associated circovirus and were even more distant to those of porcine circovirus 1 and 2. Common microscopic lesions included non-suppurative myocarditis and/or cardiac arteriolitis. Viral mRNA was detected intralesionally in cardiac cells. Deep sequencing in tissues also revealed the presence of porcine astrovirus 4 in all three animals as well as rotavirus A, porcine cytomegalovirus and porcine hemagglutinating encephalomyelitis virus in individual cases. CONCLUSION: The pathogenicity and molecular epidemiology of this new circovirus, alone or in the context of co-infections, warrants further investigations.",2016 Nov 11,"['Phan, Tung Gia', 'Giannitti, Federico', 'Rossow, Stephanie', 'Marthaler, Douglas', 'Knutson, Todd', 'Li, Linlin', 'Deng, Xutao', 'Resende, Talita', 'Vannucci, Fabio', 'Delwart, Eric']",Virol J,,,True
79b67a52cb7757c9fae9636913c30b5ee39e68af,PMC,"Chikungunya virus infectivity, RNA replication and non-structural polyprotein processing depend on the nsP2 protease’s active site cysteine residue",http://dx.doi.org/10.1038/srep37124,PMC5109220,27845418,CC BY,"Chikungunya virus (CHIKV), genus Alphavirus, family Togaviridae, has a positive-stand RNA genome approximately 12 kb in length. In infected cells, the genome is translated into non-structural polyprotein P1234, an inactive precursor of the viral replicase, which is activated by cleavages carried out by the non-structural protease, nsP2. We have characterized CHIKV nsP2 using both cell-free and cell-based assays. First, we show that Cys478 residue in the active site of CHIKV nsP2 is indispensable for P1234 processing. Second, the substrate requirements of CHIKV nsP2 are quite similar to those of nsP2 of related Semliki Forest virus (SFV). Third, substitution of Ser482 residue, recently reported to contribute to the protease activity of nsP2, with Ala has almost no negative effect on the protease activity of CHIKV nsP2. Fourth, Cys478 to Ala as well as Trp479 to Ala mutations in nsP2 completely abolished RNA replication in CHIKV and SFV trans-replication systems. In contrast, trans-replicases with Ser482 to Ala mutation were similar to wild type counterparts. Fifth, Cys478 to Ala as well as Trp479 to Ala mutations in nsP2 abolished the rescue of infectious virus from CHIKV RNA transcripts while Ser482 to Ala mutation had no effect. Thus, CHIKV nsP2 is a cysteine protease.",2016 Nov 15,"['Rausalu, Kai', 'Utt, Age', 'Quirin, Tania', 'Varghese, Finny S.', 'Žusinaite, Eva', 'Das, Pratyush Kumar', 'Ahola, Tero', 'Merits, Andres']",Sci Rep,,,True
2f0190b3d09170b52a39967ada3c55f972543d3e,PMC,"Chikungunya virus infectivity, RNA replication and non-structural polyprotein processing depend on the nsP2 protease’s active site cysteine residue",http://dx.doi.org/10.1038/srep37124,PMC5109220,27845418,CC BY,"Chikungunya virus (CHIKV), genus Alphavirus, family Togaviridae, has a positive-stand RNA genome approximately 12 kb in length. In infected cells, the genome is translated into non-structural polyprotein P1234, an inactive precursor of the viral replicase, which is activated by cleavages carried out by the non-structural protease, nsP2. We have characterized CHIKV nsP2 using both cell-free and cell-based assays. First, we show that Cys478 residue in the active site of CHIKV nsP2 is indispensable for P1234 processing. Second, the substrate requirements of CHIKV nsP2 are quite similar to those of nsP2 of related Semliki Forest virus (SFV). Third, substitution of Ser482 residue, recently reported to contribute to the protease activity of nsP2, with Ala has almost no negative effect on the protease activity of CHIKV nsP2. Fourth, Cys478 to Ala as well as Trp479 to Ala mutations in nsP2 completely abolished RNA replication in CHIKV and SFV trans-replication systems. In contrast, trans-replicases with Ser482 to Ala mutation were similar to wild type counterparts. Fifth, Cys478 to Ala as well as Trp479 to Ala mutations in nsP2 abolished the rescue of infectious virus from CHIKV RNA transcripts while Ser482 to Ala mutation had no effect. Thus, CHIKV nsP2 is a cysteine protease.",2016 Nov 15,"['Rausalu, Kai', 'Utt, Age', 'Quirin, Tania', 'Varghese, Finny S.', 'Žusinaite, Eva', 'Das, Pratyush Kumar', 'Ahola, Tero', 'Merits, Andres']",Sci Rep,,,False
fe90da34ca7b4f7fd6711bd870cb2163b8fd4ef4,PMC,Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano,http://dx.doi.org/10.1038/srep36948,PMC5109407,27845426,CC BY,"Bats are crucial for proper functioning of an ecosystem. They provide various important services to ecosystem and environment. While, bats are well-known carrier of pathogenic viruses, their possible role as a potential carrier of pathogenic bacteria is under-explored. Here, using culture-based approach, employing multiple bacteriological media, over thousand bacteria were cultivated and identified from Rousettus leschenaultii (a frugivorous bat species), the majority of which were from the family Enterobacteriaceae and putative pathogens. Next, pathogenic potential of most frequently cultivated component of microbiome i.e. Escherichia coli was assessed to identify its known pathotypes which revealed the presence of virulent factors in many cultivated E. coli isolates. Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Interestingly, a higher diversity of bacterial communities was observed in decaying guano representative. The search against human pathogenic bacteria database at 97% identity, a small proportion of sequences were found associated to well-known human pathogens. The present study thus indicates that this bat species may carry potential bacterial pathogens and advice to study the effect of these pathogens on bats itself and the probable mode of transmission to humans and other animals.",2016 Nov 15,"['Banskar, Sunil', 'Bhute, Shrikant S.', 'Suryavanshi, Mangesh V.', 'Punekar, Sachin', 'Shouche, Yogesh S.']",Sci Rep,,,True
85b681d7b41efe21e90c9fa10f67508ef7aea537,PMC,Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano,http://dx.doi.org/10.1038/srep36948,PMC5109407,27845426,CC BY,"Bats are crucial for proper functioning of an ecosystem. They provide various important services to ecosystem and environment. While, bats are well-known carrier of pathogenic viruses, their possible role as a potential carrier of pathogenic bacteria is under-explored. Here, using culture-based approach, employing multiple bacteriological media, over thousand bacteria were cultivated and identified from Rousettus leschenaultii (a frugivorous bat species), the majority of which were from the family Enterobacteriaceae and putative pathogens. Next, pathogenic potential of most frequently cultivated component of microbiome i.e. Escherichia coli was assessed to identify its known pathotypes which revealed the presence of virulent factors in many cultivated E. coli isolates. Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Interestingly, a higher diversity of bacterial communities was observed in decaying guano representative. The search against human pathogenic bacteria database at 97% identity, a small proportion of sequences were found associated to well-known human pathogens. The present study thus indicates that this bat species may carry potential bacterial pathogens and advice to study the effect of these pathogens on bats itself and the probable mode of transmission to humans and other animals.",2016 Nov 15,"['Banskar, Sunil', 'Bhute, Shrikant S.', 'Suryavanshi, Mangesh V.', 'Punekar, Sachin', 'Shouche, Yogesh S.']",Sci Rep,,,False
41acbf6dfc7569490c731f87cf3e629fc0c65b42,PMC,Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano,http://dx.doi.org/10.1038/srep36948,PMC5109407,27845426,CC BY,"Bats are crucial for proper functioning of an ecosystem. They provide various important services to ecosystem and environment. While, bats are well-known carrier of pathogenic viruses, their possible role as a potential carrier of pathogenic bacteria is under-explored. Here, using culture-based approach, employing multiple bacteriological media, over thousand bacteria were cultivated and identified from Rousettus leschenaultii (a frugivorous bat species), the majority of which were from the family Enterobacteriaceae and putative pathogens. Next, pathogenic potential of most frequently cultivated component of microbiome i.e. Escherichia coli was assessed to identify its known pathotypes which revealed the presence of virulent factors in many cultivated E. coli isolates. Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Interestingly, a higher diversity of bacterial communities was observed in decaying guano representative. The search against human pathogenic bacteria database at 97% identity, a small proportion of sequences were found associated to well-known human pathogens. The present study thus indicates that this bat species may carry potential bacterial pathogens and advice to study the effect of these pathogens on bats itself and the probable mode of transmission to humans and other animals.",2016 Nov 15,"['Banskar, Sunil', 'Bhute, Shrikant S.', 'Suryavanshi, Mangesh V.', 'Punekar, Sachin', 'Shouche, Yogesh S.']",Sci Rep,,,False
475d515546fd58bf9e9d43e9fa938817f797824a,PMC,Recalibrating disease parameters for increasing realism in modeling epidemics in closed settings,http://dx.doi.org/10.1186/s12879-016-2003-3,PMC5109722,27842507,CC BY,"BACKGROUND: The homogeneous mixing assumption is widely adopted in epidemic modelling for its parsimony and represents the building block of more complex approaches, including very detailed agent-based models. The latter assume homogeneous mixing within schools, workplaces and households, mostly for the lack of detailed information on human contact behaviour within these settings. The recent data availability on high-resolution face-to-face interactions makes it now possible to assess the goodness of this simplified scheme in reproducing relevant aspects of the infection dynamics. METHODS: We consider empirical contact networks gathered in different contexts, as well as synthetic data obtained through realistic models of contacts in structured populations. We perform stochastic spreading simulations on these contact networks and in populations of the same size under a homogeneous mixing hypothesis. We adjust the epidemiological parameters of the latter in order to fit the prevalence curve of the contact epidemic model. We quantify the agreement by comparing epidemic peak times, peak values, and epidemic sizes. RESULTS: Good approximations of the peak times and peak values are obtained with the homogeneous mixing approach, with a median relative difference smaller than 20 % in all cases investigated. Accuracy in reproducing the peak time depends on the setting under study, while for the peak value it is independent of the setting. Recalibration is found to be linear in the epidemic parameters used in the contact data simulations, showing changes across empirical settings but robustness across groups and population sizes. CONCLUSIONS: An adequate rescaling of the epidemiological parameters can yield a good agreement between the epidemic curves obtained with a real contact network and a homogeneous mixing approach in a population of the same size. The use of such recalibrated homogeneous mixing approximations would enhance the accuracy and realism of agent-based simulations and limit the intrinsic biases of the homogeneous mixing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-2003-3) contains supplementary material, which is available to authorized users.",2016 Nov 14,"['Bioglio, Livio', 'Génois, Mathieu', 'Vestergaard, Christian L.', 'Poletto, Chiara', 'Barrat, Alain', 'Colizza, Vittoria']",BMC Infect Dis,,,False
82e33ea1413ab8560304175a8281348a156c2e47,PMC,Recalibrating disease parameters for increasing realism in modeling epidemics in closed settings,http://dx.doi.org/10.1186/s12879-016-2003-3,PMC5109722,27842507,CC BY,"BACKGROUND: The homogeneous mixing assumption is widely adopted in epidemic modelling for its parsimony and represents the building block of more complex approaches, including very detailed agent-based models. The latter assume homogeneous mixing within schools, workplaces and households, mostly for the lack of detailed information on human contact behaviour within these settings. The recent data availability on high-resolution face-to-face interactions makes it now possible to assess the goodness of this simplified scheme in reproducing relevant aspects of the infection dynamics. METHODS: We consider empirical contact networks gathered in different contexts, as well as synthetic data obtained through realistic models of contacts in structured populations. We perform stochastic spreading simulations on these contact networks and in populations of the same size under a homogeneous mixing hypothesis. We adjust the epidemiological parameters of the latter in order to fit the prevalence curve of the contact epidemic model. We quantify the agreement by comparing epidemic peak times, peak values, and epidemic sizes. RESULTS: Good approximations of the peak times and peak values are obtained with the homogeneous mixing approach, with a median relative difference smaller than 20 % in all cases investigated. Accuracy in reproducing the peak time depends on the setting under study, while for the peak value it is independent of the setting. Recalibration is found to be linear in the epidemic parameters used in the contact data simulations, showing changes across empirical settings but robustness across groups and population sizes. CONCLUSIONS: An adequate rescaling of the epidemiological parameters can yield a good agreement between the epidemic curves obtained with a real contact network and a homogeneous mixing approach in a population of the same size. The use of such recalibrated homogeneous mixing approximations would enhance the accuracy and realism of agent-based simulations and limit the intrinsic biases of the homogeneous mixing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-2003-3) contains supplementary material, which is available to authorized users.",2016 Nov 14,"['Bioglio, Livio', 'Génois, Mathieu', 'Vestergaard, Christian L.', 'Poletto, Chiara', 'Barrat, Alain', 'Colizza, Vittoria']",BMC Infect Dis,,,True
642e03f3b71051b01c77af78f51bb4ef5d00ad08,PMC,Fatal Community-acquired Pneumonia in Children Caused by Re-emergent Human Adenovirus 7d Associated with Higher Severity of Illness and Fatality Rate,http://dx.doi.org/10.1038/srep37216,PMC5110970,27848998,CC BY,"Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), such as community-acquired pneumonia. HAdV-7d, a re-emergent genomic variant, has been recently reported in Asia and the United States after a several-decade absence. However, whether HAdV-7d is associated with higher severity than other types is currently unclear. In this study, the clinical and epidemiological investigation showed that fever, cough, and sore throat were the three most common respiratory symptoms of HAdV infections. HAdV-7 caused longer duration of fever, higher morbidity of tachypnea/dyspnea, pleural effusion, diarrhea, hepatosplenomegaly, consciousness alteration, as well as higher rates of pneumonia, mechanical ventilation and higher fatality rate (28.6%) than other types, particularly HAdV-3 and HAdV-2. The genomes of seven HAdV-7d isolates from mild, severe, and fatal cases were sequenced and highly similar with each other. Surprisingly, two isolates (2011, 2012) had 100% identical genomes with an earlier strain from a fatal ARD outbreak in China (2009), which elucidates the virus origin and confirms the unexpected HAdV genomic conservation and stability. Phylogenetic analysis indicated that L1 52/55-kDa DNA packaging protein may be associated with the higher severity of illness and fatality rate of HAdV-7. Clinicians need to be aware of HAdVs in children with ARD.",2016 Nov 16,"['Yu, Zhiwu', 'Zeng, Zhiwei', 'Zhang, Jing', 'Pan, Yuxian', 'Chen, Manjun', 'Guo, Yonghui', 'Yu, Nan', 'Chodosh, James', 'Fu, Ning', 'Che, Xiaoyan', 'Zhang, Qiwei']",Sci Rep,,,True
a34b4ae8ac728d948a40b4c6f0d825b319d88ad7,PMC,Coevolution of paired receptors in Xenopus carcinoembryonic antigen-related cell adhesion molecule families suggests appropriation as pathogen receptors,http://dx.doi.org/10.1186/s12864-016-3279-9,PMC5112662,27852220,CC BY,"BACKGROUND: In mammals, CEACAM1 and closely related members represent paired receptors with similar extracellular ligand-binding regions and cytoplasmic domains with opposing functions. Human CEACAM1 and CEACAM3 which have inhibitory ITIM/ITSM and activating ITAM-like motifs, respectively, in their cytoplasmic regions are such paired receptors. Various bacterial pathogens bind to CEACAM1 on epithelial and immune cells facilitating both entry into the host and down-regulation of the immune response whereas interaction with granulocyte-specific CEACAM3 leads to their uptake and destruction. It is unclear whether paired CEACAM receptors also exist in other vertebrate clades. RESULTS: We identified more than 80 ceacam genes in Xenopus tropicalis and X. laevis. They consist of two subgroups containing one or two putative paired receptor pairs each. Analysis of genomic sequences of paired receptors provide evidence that their highly similar ligand binding domains were adjusted by recent gene conversion events. In contrast, selection for diversification is observed among inhibitory receptor orthologs of the two frogs which split some 60 million years ago. The allotetraploid X. laevis arose later by hybridization of two closely related species. Interestingly, despite the conservation of the genomic landscape surrounding the homeologous ceacam loci only one locus resembles the one found in X. tropicalis. From the second X. laevis locus more than 80 % of the ceacam genes were lost including 5 of the 6 paired receptor genes. This suggests that once the gene for one of the paired receptors is lost the remaining gene cluster degrades rapidly probably due to lack of selection pressure exerted by pathogens. CONCLUSIONS: The presence of paired receptors and selection for diversification suggests that also in amphibians CEACAM1-related inhibitory proteins are or were used as pathogen receptors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3279-9) contains supplementary material, which is available to authorized users.",2016 Nov 16,"['Zimmermann, Wolfgang', 'Kammerer, Robert']",BMC Genomics,,,True
281520c659ef5b7b5561307d5a91a00526e994f3,PMC,Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia,http://dx.doi.org/10.1186/s13054-016-1517-9,PMC5112669,27852281,CC BY,"BACKGROUND: Multiplex polymerase chain reaction (mPCR) enables recovery of viruses from airways of patients with community-acquired pneumonia (CAP), although their clinical impact remains uncertain. METHODS: Among consecutive adult patients who had undergone a mPCR within 72 hours following their admission to one intensive care unit (ICU), we retrospectively included those with a final diagnosis of CAP. Four etiology groups were clustered: bacterial, viral, mixed (viral-bacterial) and no etiology. A composite criterion of complicated course (hospital death or mechanical ventilation > 7 days) was used. A subgroup analysis compared patients with bacterial and viral-bacterial CAP matched on the bacterial pathogens. RESULTS: Among 174 patients (132 men [76 %], age 63 [53–75] years, SAPSII 38 [27;55], median PSI score 106 [78;130]), bacterial, viral, mixed and no etiology groups gathered 46 (26 %), 53 (31 %), 45 (26 %) and 30 (17 %) patients, respectively. Virus-infected patients displayed a high creatine kinase serum level, a low platelet count, and a trend toward more frequent alveolar-interstitial infiltrates. A complicated course was more frequent in the mixed group (31/45, 69 %), as compared to bacterial (18/46, 39 %), viral (15/53, 28 %) and no etiology (12/30, 40 %) groups (p < 0.01). In multivariate analysis, the mixed (viral-bacterial) infection was independently associated with complicated course (reference: bacterial pneumonia; OR, 3.58; CI 95 %, 1.16–11; p = 0.03). The subgroup analysis of bacteria-matched patients confirmed these findings. CONCLUSIONS: Viral-bacterial coinfection during severe CAP in adults is associated with an impaired presentation and a complicated course. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1517-9) contains supplementary material, which is available to authorized users.",2016 Oct 25,"['Voiriot, Guillaume', 'Visseaux, Benoit', 'Cohen, Johana', 'Nguyen, Liem Binh Luong', 'Neuville, Mathilde', 'Morbieu, Caroline', 'Burdet, Charles', 'Radjou, Aguila', 'Lescure, François-Xavier', 'Smonig, Roland', 'Armand-Lefèvre, Laurence', 'Mourvillier, Bruno', 'Yazdanpanah, Yazdan', 'Soubirou, Jean-Francois', 'Ruckly, Stephane', 'Houhou-Fidouh, Nadhira', 'Timsit, Jean-François']",Crit Care,,,True
3024739cfc1f411186c0844a254501c14301c935,PMC,Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study,http://dx.doi.org/10.1371/journal.pmed.1002170,PMC5112802,27846234,CC0,"BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.",2016 Nov 15,"[None, 'Agua-Agum, Junerlyn', 'Ariyarajah, Archchun', 'Aylward, Bruce', 'Bawo, Luke', 'Bilivogui, Pepe', 'Blake, Isobel M.', 'Brennan, Richard J.', 'Cawthorne, Amy', 'Cleary, Eilish', 'Clement, Peter', 'Conteh, Roland', 'Cori, Anne', 'Dafae, Foday', 'Dahl, Benjamin', 'Dangou, Jean-Marie', 'Diallo, Boubacar', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Dye, Christopher', 'Eckmanns, Tim', 'Fallah, Mosoka', 'Ferguson, Neil M.', 'Fiebig, Lena', 'Fraser, Christophe', 'Garske, Tini', 'Gonzalez, Lice', 'Hamblion, Esther', 'Hamid, Nuha', 'Hersey, Sara', 'Hinsley, Wes', 'Jambei, Amara', 'Jombart, Thibaut', 'Kargbo, David', 'Keita, Sakoba', 'Kinzer, Michael', 'George, Fred Kuti', 'Godefroy, Beatrice', 'Gutierrez, Giovanna', 'Kannangarage, Niluka', 'Mills, Harriet L.', 'Moller, Thomas', 'Meijers, Sascha', 'Mohamed, Yasmine', 'Morgan, Oliver', 'Nedjati-Gilani, Gemma', 'Newton, Emily', 'Nouvellet, Pierre', 'Nyenswah, Tolbert', 'Perea, William', 'Perkins, Devin', 'Riley, Steven', 'Rodier, Guenael', 'Rondy, Marc', 'Sagrado, Maria', 'Savulescu, Camelia', 'Schafer, Ilana J.', 'Schumacher, Dirk', 'Seyler, Thomas', 'Shah, Anita', 'Van Kerkhove, Maria D.', 'Wesseh, C. Samford', 'Yoti, Zabulon']",PLoS Med,,,True
57b5214f988d2e84b41bccd3c704111dc73a8858,PMC,Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study,http://dx.doi.org/10.1371/journal.pmed.1002170,PMC5112802,27846234,CC0,"BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.",2016 Nov 15,"[None, 'Agua-Agum, Junerlyn', 'Ariyarajah, Archchun', 'Aylward, Bruce', 'Bawo, Luke', 'Bilivogui, Pepe', 'Blake, Isobel M.', 'Brennan, Richard J.', 'Cawthorne, Amy', 'Cleary, Eilish', 'Clement, Peter', 'Conteh, Roland', 'Cori, Anne', 'Dafae, Foday', 'Dahl, Benjamin', 'Dangou, Jean-Marie', 'Diallo, Boubacar', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Dye, Christopher', 'Eckmanns, Tim', 'Fallah, Mosoka', 'Ferguson, Neil M.', 'Fiebig, Lena', 'Fraser, Christophe', 'Garske, Tini', 'Gonzalez, Lice', 'Hamblion, Esther', 'Hamid, Nuha', 'Hersey, Sara', 'Hinsley, Wes', 'Jambei, Amara', 'Jombart, Thibaut', 'Kargbo, David', 'Keita, Sakoba', 'Kinzer, Michael', 'George, Fred Kuti', 'Godefroy, Beatrice', 'Gutierrez, Giovanna', 'Kannangarage, Niluka', 'Mills, Harriet L.', 'Moller, Thomas', 'Meijers, Sascha', 'Mohamed, Yasmine', 'Morgan, Oliver', 'Nedjati-Gilani, Gemma', 'Newton, Emily', 'Nouvellet, Pierre', 'Nyenswah, Tolbert', 'Perea, William', 'Perkins, Devin', 'Riley, Steven', 'Rodier, Guenael', 'Rondy, Marc', 'Sagrado, Maria', 'Savulescu, Camelia', 'Schafer, Ilana J.', 'Schumacher, Dirk', 'Seyler, Thomas', 'Shah, Anita', 'Van Kerkhove, Maria D.', 'Wesseh, C. Samford', 'Yoti, Zabulon']",PLoS Med,,,False
2e45df7e383ca3c79b76fa9f2acc316102386d65,PMC,Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study,http://dx.doi.org/10.1371/journal.pmed.1002170,PMC5112802,27846234,CC0,"BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.",2016 Nov 15,"[None, 'Agua-Agum, Junerlyn', 'Ariyarajah, Archchun', 'Aylward, Bruce', 'Bawo, Luke', 'Bilivogui, Pepe', 'Blake, Isobel M.', 'Brennan, Richard J.', 'Cawthorne, Amy', 'Cleary, Eilish', 'Clement, Peter', 'Conteh, Roland', 'Cori, Anne', 'Dafae, Foday', 'Dahl, Benjamin', 'Dangou, Jean-Marie', 'Diallo, Boubacar', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Dye, Christopher', 'Eckmanns, Tim', 'Fallah, Mosoka', 'Ferguson, Neil M.', 'Fiebig, Lena', 'Fraser, Christophe', 'Garske, Tini', 'Gonzalez, Lice', 'Hamblion, Esther', 'Hamid, Nuha', 'Hersey, Sara', 'Hinsley, Wes', 'Jambei, Amara', 'Jombart, Thibaut', 'Kargbo, David', 'Keita, Sakoba', 'Kinzer, Michael', 'George, Fred Kuti', 'Godefroy, Beatrice', 'Gutierrez, Giovanna', 'Kannangarage, Niluka', 'Mills, Harriet L.', 'Moller, Thomas', 'Meijers, Sascha', 'Mohamed, Yasmine', 'Morgan, Oliver', 'Nedjati-Gilani, Gemma', 'Newton, Emily', 'Nouvellet, Pierre', 'Nyenswah, Tolbert', 'Perea, William', 'Perkins, Devin', 'Riley, Steven', 'Rodier, Guenael', 'Rondy, Marc', 'Sagrado, Maria', 'Savulescu, Camelia', 'Schafer, Ilana J.', 'Schumacher, Dirk', 'Seyler, Thomas', 'Shah, Anita', 'Van Kerkhove, Maria D.', 'Wesseh, C. Samford', 'Yoti, Zabulon']",PLoS Med,,,False
3fb2c3751fc92b903123c2813868f2b7925c95be,PMC,Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study,http://dx.doi.org/10.1371/journal.pmed.1002170,PMC5112802,27846234,CC0,"BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.",2016 Nov 15,"[None, 'Agua-Agum, Junerlyn', 'Ariyarajah, Archchun', 'Aylward, Bruce', 'Bawo, Luke', 'Bilivogui, Pepe', 'Blake, Isobel M.', 'Brennan, Richard J.', 'Cawthorne, Amy', 'Cleary, Eilish', 'Clement, Peter', 'Conteh, Roland', 'Cori, Anne', 'Dafae, Foday', 'Dahl, Benjamin', 'Dangou, Jean-Marie', 'Diallo, Boubacar', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Dye, Christopher', 'Eckmanns, Tim', 'Fallah, Mosoka', 'Ferguson, Neil M.', 'Fiebig, Lena', 'Fraser, Christophe', 'Garske, Tini', 'Gonzalez, Lice', 'Hamblion, Esther', 'Hamid, Nuha', 'Hersey, Sara', 'Hinsley, Wes', 'Jambei, Amara', 'Jombart, Thibaut', 'Kargbo, David', 'Keita, Sakoba', 'Kinzer, Michael', 'George, Fred Kuti', 'Godefroy, Beatrice', 'Gutierrez, Giovanna', 'Kannangarage, Niluka', 'Mills, Harriet L.', 'Moller, Thomas', 'Meijers, Sascha', 'Mohamed, Yasmine', 'Morgan, Oliver', 'Nedjati-Gilani, Gemma', 'Newton, Emily', 'Nouvellet, Pierre', 'Nyenswah, Tolbert', 'Perea, William', 'Perkins, Devin', 'Riley, Steven', 'Rodier, Guenael', 'Rondy, Marc', 'Sagrado, Maria', 'Savulescu, Camelia', 'Schafer, Ilana J.', 'Schumacher, Dirk', 'Seyler, Thomas', 'Shah, Anita', 'Van Kerkhove, Maria D.', 'Wesseh, C. Samford', 'Yoti, Zabulon']",PLoS Med,,,False
bae235ec2b6c2fde46fd7c376d5d35933ef4f695,PMC,Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study,http://dx.doi.org/10.1371/journal.pmed.1002170,PMC5112802,27846234,CC0,"BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.",2016 Nov 15,"[None, 'Agua-Agum, Junerlyn', 'Ariyarajah, Archchun', 'Aylward, Bruce', 'Bawo, Luke', 'Bilivogui, Pepe', 'Blake, Isobel M.', 'Brennan, Richard J.', 'Cawthorne, Amy', 'Cleary, Eilish', 'Clement, Peter', 'Conteh, Roland', 'Cori, Anne', 'Dafae, Foday', 'Dahl, Benjamin', 'Dangou, Jean-Marie', 'Diallo, Boubacar', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Dye, Christopher', 'Eckmanns, Tim', 'Fallah, Mosoka', 'Ferguson, Neil M.', 'Fiebig, Lena', 'Fraser, Christophe', 'Garske, Tini', 'Gonzalez, Lice', 'Hamblion, Esther', 'Hamid, Nuha', 'Hersey, Sara', 'Hinsley, Wes', 'Jambei, Amara', 'Jombart, Thibaut', 'Kargbo, David', 'Keita, Sakoba', 'Kinzer, Michael', 'George, Fred Kuti', 'Godefroy, Beatrice', 'Gutierrez, Giovanna', 'Kannangarage, Niluka', 'Mills, Harriet L.', 'Moller, Thomas', 'Meijers, Sascha', 'Mohamed, Yasmine', 'Morgan, Oliver', 'Nedjati-Gilani, Gemma', 'Newton, Emily', 'Nouvellet, Pierre', 'Nyenswah, Tolbert', 'Perea, William', 'Perkins, Devin', 'Riley, Steven', 'Rodier, Guenael', 'Rondy, Marc', 'Sagrado, Maria', 'Savulescu, Camelia', 'Schafer, Ilana J.', 'Schumacher, Dirk', 'Seyler, Thomas', 'Shah, Anita', 'Van Kerkhove, Maria D.', 'Wesseh, C. Samford', 'Yoti, Zabulon']",PLoS Med,,,False
c59a2273688935323baa77faa5363abd22009134,PMC,Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study,http://dx.doi.org/10.1371/journal.pmed.1002170,PMC5112802,27846234,CC0,"BACKGROUND: The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. METHODS AND FINDINGS: Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). CONCLUSIONS: Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.",2016 Nov 15,"[None, 'Agua-Agum, Junerlyn', 'Ariyarajah, Archchun', 'Aylward, Bruce', 'Bawo, Luke', 'Bilivogui, Pepe', 'Blake, Isobel M.', 'Brennan, Richard J.', 'Cawthorne, Amy', 'Cleary, Eilish', 'Clement, Peter', 'Conteh, Roland', 'Cori, Anne', 'Dafae, Foday', 'Dahl, Benjamin', 'Dangou, Jean-Marie', 'Diallo, Boubacar', 'Donnelly, Christl A.', 'Dorigatti, Ilaria', 'Dye, Christopher', 'Eckmanns, Tim', 'Fallah, Mosoka', 'Ferguson, Neil M.', 'Fiebig, Lena', 'Fraser, Christophe', 'Garske, Tini', 'Gonzalez, Lice', 'Hamblion, Esther', 'Hamid, Nuha', 'Hersey, Sara', 'Hinsley, Wes', 'Jambei, Amara', 'Jombart, Thibaut', 'Kargbo, David', 'Keita, Sakoba', 'Kinzer, Michael', 'George, Fred Kuti', 'Godefroy, Beatrice', 'Gutierrez, Giovanna', 'Kannangarage, Niluka', 'Mills, Harriet L.', 'Moller, Thomas', 'Meijers, Sascha', 'Mohamed, Yasmine', 'Morgan, Oliver', 'Nedjati-Gilani, Gemma', 'Newton, Emily', 'Nouvellet, Pierre', 'Nyenswah, Tolbert', 'Perea, William', 'Perkins, Devin', 'Riley, Steven', 'Rodier, Guenael', 'Rondy, Marc', 'Sagrado, Maria', 'Savulescu, Camelia', 'Schafer, Ilana J.', 'Schumacher, Dirk', 'Seyler, Thomas', 'Shah, Anita', 'Van Kerkhove, Maria D.', 'Wesseh, C. Samford', 'Yoti, Zabulon']",PLoS Med,,,False
15a5a243bb623a17ee4f0c18c4e3bea8c065ed11,PMC,Transmissible Gastroenteritis Virus Infection Enhances SGLT1 and GLUT2 Expression to Increase Glucose Uptake,http://dx.doi.org/10.1371/journal.pone.0165585,PMC5112927,27851758,CC BY,"Transmissible gastroenteritis virus (TGEV) is a coronavirus that causes villus atrophy, followed by crypt hyperplasia, reduces the activities of intestinal digestive enzymes, and disrupts the absorption of intestinal nutrients. In vivo, TGEV primarily targets and infects intestinal epithelial cells, which play an important role in glucose absorption via the apical and basolateral transporters Na(+)-dependent glucose transporter 1 (SGLT1) and facilitative glucose transporter 2 (GLUT2), respectively. In this study, we therefore sought to evaluate the effects of TGEV infection on glucose uptake and SGLT1 and GLUT2 expression. Our data demonstrate that infection with TGEV resulted in increased glucose uptake and augmented expression of EGFR, SGLT1 and GLUT2. Moreover, inhibition studies showed that EGFR modulated glucose uptake in control and TGEV infected cells. Finally, high glucose absorption was subsequently found to promote TGEV replication.",2016 Nov 16,"['Dai, Lei', 'Hu, Wei Wei', 'Xia, Lu', 'Xia, Mi', 'Yang, Qian']",PLoS One,,,True
e55459a4991dbc5ed150ee9174b48401b24517fc,PMC,"Epidemiologic investigation of a family cluster of imported ZIKV cases in Guangdong, China: probable human-to-human transmission",http://dx.doi.org/10.1038/emi.2016.100,PMC5113051,27599469,CC BY,"Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that can potentially threaten South China. A Chinese family of four returning from Venezuela to China was found to be positive for ZIKV when the youngest son's fever was first detected at an airport immigration inspection. They were isolated temporarily in a local hospital in Enping city, Guangdong province, where their clinical data were recorded and urine and saliva were collected to isolate ZIKV and to obtain viral sequences. All of them except the mother presented mild symptoms of rash and fever. Envelope gene sequences from the father, daughter and son were completely identical. Phylogenetic analysis demonstrated that this strain is similar to several imported strains reported in recent months, which are all clustered into a group isolated from 2015 ZIKA outbreaks in Brazil. Together with the climatic features in Venezuela, New York and Guangdong in February, it can be concluded that our subjects are imported cases from Venezuela. With the same viral sequence being shared between family members, neither direct human-to-human nor vector transmission can be ruled out in this study, but the former seems more likely. Although our subjects had mild illness, epidemiologists and public health officials should be aware of the risk of further expansion of ZIKV transmission by local competent vectors.",2016 Sep 7,"['Yin, Yingxian', 'Xu, Yi', 'Su, Ling', 'Zhu, Xun', 'Chen, Minxia', 'Zhu, Weijin', 'Xia, Huimin', 'Huang, Xi', 'Gong, Sitang']",Emerg Microbes Infect,,,True
cc65afbab3c952058f9261b012cdc4407a9d264c,PMC,Evidence that Processing of the Severe Fever with Thrombocytopenia Syndrome Virus Gn/Gc Polyprotein Is Critical for Viral Infectivity and Requires an Internal Gc Signal Peptide,http://dx.doi.org/10.1371/journal.pone.0166013,PMC5113920,27855227,CC BY,"The severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging, highly pathogenic bunyavirus against which neither antivirals nor vaccines are available. The SFTSV glycoproteins, Gn and Gc, facilitate viral entry into host cells. Gn and Gc are generated from a precursor protein, Gn/Gc, but it is currently unknown how the precursor is converted into the single proteins and whether this process is required for viral infectivity. Employing a rhabdoviral pseudotyping system, we demonstrate that a predicted signal sequence at the N-terminus of Gc is required for Gn/Gc processing and viral infectivity while potential proprotein convertase cleavage sites in Gc are dispensable. Moreover, we show that expression of Gn or Gc alone is not sufficient for host cell entry while particles bearing both proteins are infectious, and we provide evidence that Gn facilitates Golgi transport and virion incorporation of Gc. Collectively, these results suggest that signal peptidase liberates mature Gc from the Gn/Gc precursor and that this process is essential for viral infectivity and thus constitutes a potential target for antiviral intervention.",2016 Nov 17,"['Plegge, Teresa', 'Hofmann-Winkler, Heike', 'Spiegel, Martin', 'Pöhlmann, Stefan']",PLoS One,,,True
4d5640c129096fd8a4da9d32030420def86285e5,PMC,Zika (PRVABC59) Infection Is Associated with T cell Infiltration and Neurodegeneration in CNS of Immunocompetent Neonatal C57Bl/6 Mice,http://dx.doi.org/10.1371/journal.ppat.1006004,PMC5113993,27855206,CC0,"The recent spread of Zika virus (ZIKV) and its association with increased rates of Guillain Barre and other neurological disorders as well as congenital defects that include microcephaly has created an urgent need to develop animal models to examine the pathogenesis of the disease and explore the efficacy of potential therapeutics and vaccines. Recently developed infection models for ZIKV utilize mice defective in interferon responses. In this study we establish and characterize a new model of peripheral ZIKV infection using immunocompetent neonatal C57BL/6 mice and compare its clinical progression, virus distribution, immune response, and neuropathology with that of C57BL/6-IFNAR KO mice. We show that while ZIKV infected IFNAR KO mice develop bilateral hind limb paralysis and die 5–6 days post-infection (dpi), immunocompetent B6 WT mice develop signs of neurological disease including unsteady gait, kinetic tremors, severe ataxia and seizures by 13 dpi that subside gradually over 2 weeks. Immunohistochemistry show viral antigen predominantly in cerebellum at the peak of the disease in both models. However, whereas IFNAR KO mice showed infiltration by neutrophils and macrophages and higher expression of IL-1, IL-6 and Cox2, B6 WT mice show a cellular infiltration in the CNS composed predominantly of T cells, particularly CD8+ T cells, and increased mRNA expression levels of IFNg, GzmB and Prf1 at peak of disease. Lastly, the CNS of B6 WT mice shows evidence of neurodegeneration predominantly in the cerebellum that are less prominent in mice lacking the IFN response possibly due to the difference in cellular infiltrates and rapid progression of the disease in that model. The development of the B6 WT model of ZIKV infection will provide insight into the immunopathology of the virus and facilitate assessments of possible therapeutics and vaccines.",2016 Nov 17,"['Manangeeswaran, Mohanraj', 'Ireland, Derek D. C.', 'Verthelyi, Daniela']",PLoS Pathog,,,True
5327ced6851fc0a01061c44f38d7e6c1244dd455,PMC,Zika (PRVABC59) Infection Is Associated with T cell Infiltration and Neurodegeneration in CNS of Immunocompetent Neonatal C57Bl/6 Mice,http://dx.doi.org/10.1371/journal.ppat.1006004,PMC5113993,27855206,CC0,"The recent spread of Zika virus (ZIKV) and its association with increased rates of Guillain Barre and other neurological disorders as well as congenital defects that include microcephaly has created an urgent need to develop animal models to examine the pathogenesis of the disease and explore the efficacy of potential therapeutics and vaccines. Recently developed infection models for ZIKV utilize mice defective in interferon responses. In this study we establish and characterize a new model of peripheral ZIKV infection using immunocompetent neonatal C57BL/6 mice and compare its clinical progression, virus distribution, immune response, and neuropathology with that of C57BL/6-IFNAR KO mice. We show that while ZIKV infected IFNAR KO mice develop bilateral hind limb paralysis and die 5–6 days post-infection (dpi), immunocompetent B6 WT mice develop signs of neurological disease including unsteady gait, kinetic tremors, severe ataxia and seizures by 13 dpi that subside gradually over 2 weeks. Immunohistochemistry show viral antigen predominantly in cerebellum at the peak of the disease in both models. However, whereas IFNAR KO mice showed infiltration by neutrophils and macrophages and higher expression of IL-1, IL-6 and Cox2, B6 WT mice show a cellular infiltration in the CNS composed predominantly of T cells, particularly CD8+ T cells, and increased mRNA expression levels of IFNg, GzmB and Prf1 at peak of disease. Lastly, the CNS of B6 WT mice shows evidence of neurodegeneration predominantly in the cerebellum that are less prominent in mice lacking the IFN response possibly due to the difference in cellular infiltrates and rapid progression of the disease in that model. The development of the B6 WT model of ZIKV infection will provide insight into the immunopathology of the virus and facilitate assessments of possible therapeutics and vaccines.",2016 Nov 17,"['Manangeeswaran, Mohanraj', 'Ireland, Derek D. C.', 'Verthelyi, Daniela']",PLoS Pathog,,,False
e8f7192873a7eab54d8f845f5bf5fc450cbe2e37,PMC,Respiratory viral infections and host responses; insights from genomics,http://dx.doi.org/10.1186/s12931-016-0474-9,PMC5117516,27871304,CC BY,"Respiratory viral infections are a leading cause of disease and mortality. The severity of these illnesses can vary markedly from mild or asymptomatic upper airway infections to severe wheezing, bronchiolitis or pneumonia. In this article, we review the viral sensing pathways and organizing principles that govern the innate immune response to infection. Then, we reconstruct the molecular networks that differentiate symptomatic from asymptomatic respiratory viral infections, and identify the underlying molecular drivers of these networks. Finally, we discuss unique aspects of the biology and pathogenesis of infections with respiratory syncytial virus, rhinovirus and influenza, drawing on insights from genomics.",2016 Nov 21,"['Troy, Niamh M.', 'Bosco, Anthony']",Respir Res,,,True
8be925093133c499cb2c93e36d9bf0fdb24c2eda,PMC,"Ebola, Zika and the International Health Regulations – implications for Port Health Preparedness",http://dx.doi.org/10.1186/s12992-016-0173-9,PMC5117607,27871327,CC BY,"BACKGROUND: The outbreak of Ebola Virus Disease in West Africa in 2014-2015 was unprecedented in terms of its scale and consequence. This, together with the emergence of Zika virus as a Public Health Emergency of International Concern in 2016, has again highlighted the potential for disease to spread across international borders and provided an impetus for countries to review their Port Health preparedness. This report reviews the legislative framework and actions taken under this framework in advancing and improving Port Health preparedness in Ireland, in response to the declaration of the Public Health Emergency of International Concern for Ebola Virus Disease in August 2014. FINDINGS: Infectious disease Shipping and Aircraft Regulations were brought into force in Ireland in 2008 and 2009, respectively. Preparatory actions taken under these and the International Health Regulations necessitated significant levels of cross disciplinary working with other organisations, both within and beyond traditional healthcare settings. Information packs on Ebola Virus Disease were prepared and distributed to airports, airlines, port authorities and shipping agents, and practical exercises were held at relevant sites. Agreements were put in place for contact tracing of passenger and crew on affected conveyances and protocols were established for the management of Medical Declarations of Health from ships coming from West Africa. CONCLUSIONS: The outbreak of Ebola Virus Disease in West Africa resulted in significant strengthening of Ireland’s Port Health preparedness, while also highlighting the extent to which preparedness requires ongoing and sustained commitment from all stakeholders, both nationally and internationally, in ensuring that countries are ready when the next threat presents at their borders.",2016 Nov 21,"['Glynn, R. W.', 'Boland, M.', None]",Global Health,,,True
c6e2851ef1f6e35c2954eeaa913f2da2502842d9,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,True
e8fee5ad6649972750c54158e4fff759beb12d3b,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
46bbc1a9a5cb04f9e2156e26842f1aa6d1ead14a,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
9871ce7a904960426816c71415696441aff8bcc3,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
0d40a575b734448ffdb8b7e20db9075295c4dbf2,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
4be99efe3b1b8c8a1ea1fad11a541ad437798ee7,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
a98cc3c7c41072d33b8382a8b6fb2cac6243e598,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
0d1b4776233a32404ee6fcba5cac809e15e3732f,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
ea6b9bf12c54a99f7304353af992637e589a0eef,PMC,Evolution of codon usage in Zika virus genomes is host and vector specific,http://dx.doi.org/10.1038/emi.2016.106,PMC5117728,27729643,CC BY,"The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.",2016 Oct 12,"['Butt, Azeem Mehmood', 'Nasrullah, Izza', 'Qamar, Raheel', 'Tong, Yigang']",Emerg Microbes Infect,,,False
b7de4f4a99e8da86891ed28bca52afcbcbdabfa1,PMC,Increased frequency of porcine epidemic diarrhea virus shedding and lesions in suckling pigs compared to nursery pigs and protective immunity in nursery pigs after homologous re-challenge,http://dx.doi.org/10.1186/s13567-016-0402-5,PMC5118895,27871312,CC BY,"Porcine epidemic diarrhea virus (PEDV) causes enteric disease in pigs and spreads rapidly after entering naïve pig populations. The objectives were to (1) compare the disease course following inoculation with PEDV isolate US/Colorado/2013 in naïve 10 day and 8 week-old pigs, and (2) contrast the naïve response to homologous challenge in 8 week-old pigs. Pigs were randomly assigned into group 1 (n = 40, no PEDV exposure), group 2 (n = 43, PEDV inoculation at 10 days of age) and group 3 (n = 48, PEDV inoculation at 8 weeks of age). Thirty-three group 2 pigs received a homologous challenge at 8 weeks of age. Following primary or secondary inoculation, 3–10 pigs were euthanized at days post-inoculation (dpi) 1, 2, 3, 7 or 14. Clinical signs were more pronounced in 10 day-old pigs compared to 8 week-old pigs at dpi 2 and 3, a higher number of 10 day-old pigs shed PEDV RNA in feces compared to 8 week-old pigs. Typical severe atrophic enteritis of PEDV infection was observed at dpi 3 in both age groups, and at dpi 4 and 14 fecal shedding patterns were also similar. While both age groups had seroconverted to PEDV by dpi 14, IgG levels were higher in 8 week-old pigs. PEDV IgA antibodies were detected in feces of approximately 50% of the pigs at dpi 44. In homologous challenged pigs, no clinical signs or lesions were found, and PEDV fecal shedding was restricted to less than 10% of the pigs indicating the existence of homologous protection 44 days after initial PEDV exposure.",2016 Nov 21,"['Gerber, Priscilla F.', 'Xiao, Chao-Ting', 'Lager, Kelly', 'Crawford, Kimberly', 'Kulshreshtha, Vikas', 'Cao, Dianjun', 'Meng, Xiang-Jin', 'Opriessnig, Tanja']",Vet Res,,,True
f421ab87adfb959664409ada2f3849ec1a977320,PMC,"Enterovirus D68 in Hospitalized Children: Sequence Variation, Viral Loads and Clinical Outcomes",http://dx.doi.org/10.1371/journal.pone.0167111,PMC5119825,27875593,CC BY,"BACKGROUND: An outbreak of enterovirus D68 (EV-D68) caused severe respiratory illness in 2014. The disease spectrum of EV-D68 infections in children with underlying medical conditions other than asthma, the role of EV-D68 loads on clinical illness, and the variation of EV-D68 strains within the same institution over time have not been described. We sought to define the association between EV-D68 loads and sequence variation, and the clinical characteristic in hospitalized children at our institution from 2011 to 2014. METHODS: May through November 2014, and August to September 2011 to 2013, a convenience sample of nasopharyngeal specimens from children with rhinovirus (RV)/EV respiratory infections were tested for EV-D68 by RT-PCR. Clinical data were compared between children with RV/EV-non-EV-D68 and EV-D68 infections, and among children with EV-D68 infections categorized as healthy, asthmatics, and chronic medical conditions. EV-D68 loads were analyzed in relation to disease severity parameters and sequence variability characterized over time. RESULTS: In 2014, 44% (192/438) of samples tested positive for EV-D68 vs. 10% (13/130) in 2011–13 (p<0.0001). PICU admissions (p<0.0001) and non-invasive ventilation (p<0.0001) were more common in children with EV-D68 vs. RV/EV-non-EV-D68 infections. Asthmatic EV-D68+ children, required supplemental oxygen administration (p = 0.03) and PICU admissions (p <0.001) more frequently than healthy children or those with chronic medical conditions; however oxygen duration (p<0.0001), and both PICU and total hospital stay (p<0.01) were greater in children with underlying medical conditions, irrespective of viral burden. By phylogenetic analysis, the 2014 EV-D68 strains clustered into a new sublineage within clade B. CONCLUSIONS: This is one of the largest pediatric cohorts described from the EV-D68 outbreak. Irrespective of viral loads, EV-D68 was associated with high morbidity in children with asthma and co-morbidities. While EV-D68 circulated before 2014, the outbreak isolates clustered differently than those from prior years.",2016 Nov 22,"['Moyer, Katherine', 'Wang, Huanyu', 'Salamon, Douglas', 'Leber, Amy', 'Mejias, Asuncion']",PLoS One,,,True
c933e09cb9262b2edc2394b1a7d86357da840493,PMC,High Diversity of Genogroup I Picobirnaviruses in Mammals,http://dx.doi.org/10.3389/fmicb.2016.01886,PMC5120130,27933049,CC BY,"In a molecular epidemiology study using 791 fecal samples collected from different terrestrial and marine mammals in Hong Kong, genogroup I picobirnaviruses (PBVs) were positive by RT-PCR targeting the partial RdRp gene in specimens from five cattle, six monkeys, 17 horses, nine pigs, one rabbit, one dog, and 12 California sea lions, with 11, 9, 23, 17, 1, 1, and 15 sequence types in the positive specimens from the corresponding animals, respectively. Phylogenetic analysis showed that the PBV sequences from each kind of animal were widely distributed in the whole tree with high diversity, sharing 47.4–89.0% nucleotide identities with other genogroup I PBV strains based on the partial RdRp gene. Nine complete segment 1 (viral loads 1.7 × 10(4) to 5.9 × 10(6)/ml) and 15 segment 2 (viral loads 4.1 × 10(3) to 1.3 × 10(6)/ml) of otarine PBVs from fecal samples serially collected from California sea lions were sequenced. In the two phylogenetic trees constructed using ORF2 and ORF3 of segment 1, the nine segment 1 sequences were clustered into four distinct clades (C1–C4). In the tree constructed using RdRp gene of segment 2, the 15 segment 2 sequences were clustered into nine distinct clades (R1–R9). In four sea lions, PBVs were detected in two different years, with the same segment 1 clade (C3) present in two consecutive years from one sea lion and different clades present in different years from three sea lions. A high diversity of PBVs was observed in a variety of terrestrial and marine mammals. Multiple sequence types with significant differences, representing multiple strains of PBV, were present in the majority of PBV-positive samples from different kinds of animals.",2016 Nov 23,"['Woo, Patrick C. Y.', 'Teng, Jade L. L.', 'Bai, Ru', 'Wong, Annette Y. P.', 'Martelli, Paolo', 'Hui, Suk-Wai', 'Tsang, Alan K. L.', 'Lau, Candy C. Y.', 'Ahmed, Syed S.', 'Yip, Cyril C. Y.', 'Choi, Garnet K. Y.', 'Li, Kenneth S. M.', 'Lam, Carol S. F.', 'Lau, Susanna K. P.', 'Yuen, Kwok-Yung']",Front Microbiol,,,True
94ccf97f5df377bf432fa3a831e38f11985965bd,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,True
e435b69dbcf8f58770a536cd0f429238fa3368f6,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
3b831e1792c447aed55f2eee0c1d0c75b2372dbb,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
2fa60d44d0d8c4737fd1e18d9b046f584bea2549,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
4c8110bfcde6d110c4a455f7bb8ea1a7801e8434,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
db36b989b9a9b5e309143650fca156e2613c034d,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
b9e757940f9d429f2684ee74b0e965f888ed973e,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
0f3ed61e7fb715fd7fdbc2e3a302b6b879e9b2af,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
b0089c74fa2043dfa4ffe2823b080792ca14ad76,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
ba70c25d879ca4243b2e05433c4e77efe3e4e263,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
8f0f34b6fdee81589f6e57a784dc4bafb0a9a6a1,PMC,Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants,http://dx.doi.org/10.1128/mSphere.00312-16,PMC5120172,27904883,CC BY,"Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.",2016 Nov 23,"['Korten, Insa', 'Mika, Moana', 'Klenja, Shkipe', 'Kieninger, Elisabeth', 'Mack, Ines', 'Barbani, Maria Teresa', 'Gorgievski, Meri', 'Frey, Urs', 'Hilty, Markus', 'Latzin, Philipp']",mSphere,,,False
d7803599fa57f39b06d7fd5bc8986420ae13fc2c,PMC,"Identification of an infectious bronchitis coronavirus strain exhibiting a classical genotype but altered antigenicity, pathogenicity, and innate immunity profile",http://dx.doi.org/10.1038/srep37725,PMC5120290,27876864,CC BY,"Avian coronavirus infectious bronchitis virus (IBV) poses economic threat to the poultry industry worldwide. Pathogenic IBV 3575/08 was isolated from broilers vaccinated with the attenuated viral vaccine derived from a Taiwan strain 2575/98. In this study, extensive investigations were conducted on the genome sequences, antigenicity, pathogenicity, and host immune responses of several IBV strains in specific-pathogen-free chickens. Sequence analyses revealed that 3575/08 and 2575/98 shared high homology in their structural genes, but not in non-structural accessory proteins such as 3a, 3b and 5b. Despite a high degree of homology in their spike protein genes, cross neutralization test showed low cross protection between 3575/08 and 2575/98, suggesting distinct antigenicity for the two strains. Animal challenge experiments exhibited strong respiratory and renal pathogenicity for 3575/08. In addition, early and prolonged viral shedding and rapid viral dissemination were observed. Immune gene expression profiling by PCR array showed chickens infected with 3575/08 had delayed expression of a subset of early innate immune genes, whereas chickens infected with the wild-type or attenuated-type 2575/08 revealed quick gene induction and efficient virus control. In summary, this study reveals a new IBV strain, which harbors a known local genotype but displays remarkably altered antigenicity, pathogenicity and host defenses.",2016 Nov 23,"['Lin, Shu-Yi', 'Li, Yao-Tsun', 'Chen, You-Ting', 'Chen, Ting-Chih', 'Hu, Che-Ming J.', 'Chen, Hui-Wen']",Sci Rep,,,True
8aa377ebe7d8486e4d0e38f6542eb40c0ab31847,PMC,"Identification of an infectious bronchitis coronavirus strain exhibiting a classical genotype but altered antigenicity, pathogenicity, and innate immunity profile",http://dx.doi.org/10.1038/srep37725,PMC5120290,27876864,CC BY,"Avian coronavirus infectious bronchitis virus (IBV) poses economic threat to the poultry industry worldwide. Pathogenic IBV 3575/08 was isolated from broilers vaccinated with the attenuated viral vaccine derived from a Taiwan strain 2575/98. In this study, extensive investigations were conducted on the genome sequences, antigenicity, pathogenicity, and host immune responses of several IBV strains in specific-pathogen-free chickens. Sequence analyses revealed that 3575/08 and 2575/98 shared high homology in their structural genes, but not in non-structural accessory proteins such as 3a, 3b and 5b. Despite a high degree of homology in their spike protein genes, cross neutralization test showed low cross protection between 3575/08 and 2575/98, suggesting distinct antigenicity for the two strains. Animal challenge experiments exhibited strong respiratory and renal pathogenicity for 3575/08. In addition, early and prolonged viral shedding and rapid viral dissemination were observed. Immune gene expression profiling by PCR array showed chickens infected with 3575/08 had delayed expression of a subset of early innate immune genes, whereas chickens infected with the wild-type or attenuated-type 2575/08 revealed quick gene induction and efficient virus control. In summary, this study reveals a new IBV strain, which harbors a known local genotype but displays remarkably altered antigenicity, pathogenicity and host defenses.",2016 Nov 23,"['Lin, Shu-Yi', 'Li, Yao-Tsun', 'Chen, You-Ting', 'Chen, Ting-Chih', 'Hu, Che-Ming J.', 'Chen, Hui-Wen']",Sci Rep,,,False
f4a82ad66962355ffb09e4d1b57fde3e94f0ec53,PMC,Regulation and Maintenance of an Adoptive T-Cell Dependent Memory B Cell Pool,http://dx.doi.org/10.1371/journal.pone.0167003,PMC5120830,27880797,CC BY,"We investigated the ability of monoclonal B cells to restore primary and secondary T-cell dependent antibody responses in adoptive immune-deficient hosts. Priming induced B cell activation and expansion, AID expression, antibody production and the generation of IgM(+)IgG(-) and IgM(-)IgG(+) antigen-experienced B-cell subsets that persisted in the lymphopenic environment by cell division. Upon secondary transfer and recall the IgM(-)IgG(+) cells responded by the production of antigen-specific IgG while the IgM(+) memory cells secreted mainly IgM and little IgG, but generated new B cells expressing germinal center markers. The recall responses were more efficient if the antigenic boost was delayed suggesting that a period of adaptation is necessary before the transferred cells are able to respond. Overall these findings indicate that reconstitution of a functional and complete memory pool requires transfer of all different antigen-experienced B cell subsets. We also found that the size of the memory B cell pool did not rely on the number of the responding naïve B cells, suggesting autonomous homeostatic controls for naïve and memory B cells. By reconstituting a stable memory B cell pool in immune-deficient hosts using a monoclonal high-affinity B cell population we demonstrate the potential value of B cell adoptive immunotherapy.",2016 Nov 23,"['Anson, Marie', 'Amado, Inês', 'Mailhé, Marie-Pierre', 'Donnadieu, Emmanuel', 'Garcia, Sylvie', 'Huetz, François', 'Freitas, Antonio A.']",PLoS One,,,True
0792384d074cef963c808eacf3c63e3654776a2a,PMC,Viral Infection in the Development and Progression of Pediatric Acute Respiratory Distress Syndrome,http://dx.doi.org/10.3389/fped.2016.00128,PMC5121220,27933286,CC BY,"Viral infections are an important cause of pediatric acute respiratory distress syndrome (ARDS). Numerous viruses, including respiratory syncytial virus (RSV) and influenza A (H1N1) virus, have been implicated in the progression of pneumonia to ARDS; yet the incidence of progression is unknown. Despite acute and chronic morbidity associated with respiratory viral infections, particularly in “at risk” populations, treatment options are limited. Thus, with few exceptions, care is symptomatic. In addition, mortality rates for viral-related ARDS have yet to be determined. This review outlines what is known about ARDS secondary to viral infections including the epidemiology, the pathophysiology, and diagnosis. In addition, emerging treatment options to prevent infection, and to decrease disease burden will be outlined. We focused on RSV and influenza A (H1N1) viral-induced ARDS, as these are the most common viruses leading to pediatric ARDS, and have specific prophylactic and definitive treatment options.",2016 Nov 24,"['Nye, Steven', 'Whitley, Richard J.', 'Kong, Michele']",Front Pediatr,,,True
985f2253ef842c0bd15013ac3314061d880d12a4,PMC,Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines,http://dx.doi.org/10.1038/ncomms13473,PMC5121417,27874853,CC BY,"Viral subunit vaccines often contain immunodominant non-neutralizing epitopes that divert host immune responses. These epitopes should be eliminated in vaccine design, but there is no reliable method for evaluating an epitope's capacity to elicit neutralizing immune responses. Here we introduce a new concept ‘neutralizing immunogenicity index' (NII) to evaluate an epitope's neutralizing immunogenicity. To determine the NII, we mask the epitope with a glycan probe and then assess the epitope's contribution to the vaccine's overall neutralizing immunogenicity. As proof-of-concept, we measure the NII for different epitopes on an immunogen comprised of the receptor-binding domain from MERS coronavirus (MERS-CoV). Further, we design a variant form of this vaccine by masking an epitope that has a negative NII score. This engineered vaccine demonstrates significantly enhanced efficacy in protecting transgenic mice from lethal MERS-CoV challenge. Our study may guide the rational design of highly effective subunit vaccines to combat MERS-CoV and other life-threatening viruses.",2016 Nov 22,"['Du, Lanying', 'Tai, Wanbo', 'Yang, Yang', 'Zhao, Guangyu', 'Zhu, Qing', 'Sun, Shihui', 'Liu, Chang', 'Tao, Xinrong', 'Tseng, Chien-Te K.', 'Perlman, Stanley', 'Jiang, Shibo', 'Zhou, Yusen', 'Li, Fang']",Nat Commun,,,True
d98fdaef5cdea0bb192c21a1a234df3d506290d6,PMC,Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines,http://dx.doi.org/10.1038/ncomms13473,PMC5121417,27874853,CC BY,"Viral subunit vaccines often contain immunodominant non-neutralizing epitopes that divert host immune responses. These epitopes should be eliminated in vaccine design, but there is no reliable method for evaluating an epitope's capacity to elicit neutralizing immune responses. Here we introduce a new concept ‘neutralizing immunogenicity index' (NII) to evaluate an epitope's neutralizing immunogenicity. To determine the NII, we mask the epitope with a glycan probe and then assess the epitope's contribution to the vaccine's overall neutralizing immunogenicity. As proof-of-concept, we measure the NII for different epitopes on an immunogen comprised of the receptor-binding domain from MERS coronavirus (MERS-CoV). Further, we design a variant form of this vaccine by masking an epitope that has a negative NII score. This engineered vaccine demonstrates significantly enhanced efficacy in protecting transgenic mice from lethal MERS-CoV challenge. Our study may guide the rational design of highly effective subunit vaccines to combat MERS-CoV and other life-threatening viruses.",2016 Nov 22,"['Du, Lanying', 'Tai, Wanbo', 'Yang, Yang', 'Zhao, Guangyu', 'Zhu, Qing', 'Sun, Shihui', 'Liu, Chang', 'Tao, Xinrong', 'Tseng, Chien-Te K.', 'Perlman, Stanley', 'Jiang, Shibo', 'Zhou, Yusen', 'Li, Fang']",Nat Commun,,,False
bca82a8723c167333ef1d73d5bf0fd900f30b695,PMC,Phenotypic and functional characterization of the major lymphocyte populations in the fruit-eating bat Pteropus alecto,http://dx.doi.org/10.1038/srep37796,PMC5121612,27883085,CC BY,"The unique ability of bats to act as reservoir for viruses that are highly pathogenic to humans suggests unique properties and functional characteristics of their immune system. However, the lack of bat specific reagents, in particular antibodies, has limited our knowledge of bat’s immunity. Using cross-reactive antibodies, we report the phenotypic and functional characterization of T cell subsets, B and NK cells in the fruit-eating bat Pteropus alecto. Our findings indicate the predominance of CD8(+) T cells in the spleen from wild-caught bats that may reflect either the presence of viruses in this organ or predominance of this cell subset at steady state. Instead majority of T cells in circulation, lymph nodes and bone marrow (BM) were CD4(+) subsets. Interestingly, 40% of spleen T cells expressed constitutively IL-17, IL-22 and TGF-β mRNA, which may indicate a strong bias towards the Th17 and regulatory T cell subsets. Furthermore, the unexpected high number of T cells in bats BM could suggest an important role in T cell development. Finally, mitogenic stimulation induced proliferation and production of effector molecules by bats immune cells. This work contributes to a better understanding of bat’s immunity, opening up new perspectives of therapeutic interventions for humans.",2016 Nov 24,"['Martínez Gómez, Julia María', 'Periasamy, Pravin', 'Dutertre, Charles-Antoine', 'Irving, Aaron Trent', 'Ng, Justin Han Jia', 'Crameri, Gary', 'Baker, Michelle L.', 'Ginhoux, Florent', 'Wang, Lin-Fa', 'Alonso, Sylvie']",Sci Rep,,,True
65aad42469b115f496dac7fe5b1a74ee5bbbf93e,PMC,Mint3/Apba3 depletion ameliorates severe murine influenza pneumonia and macrophage cytokine production in response to the influenza virus,http://dx.doi.org/10.1038/srep37815,PMC5121658,27883071,CC BY,"Influenza virus (IFV) infection is a common cause of severe pneumonia. Studies have suggested that excessive activation of the host immune system including macrophages is responsible for the severe pathologies mediated by IFV infection. Here, we focused on the X11 protein family member Mint3/Apba3, known to promote ATP production via glycolysis by activating hypoxia inducible factor-1 (HIF-1) in macrophages, and examined its roles in lung pathogenesis and anti-viral defence upon IFV infection. Mint3-deficient mice exhibited improved influenza pneumonia with reduced inflammatory cytokines/chemokine levels and neutrophil infiltration in the IFV-infected lungs without alteration in viral burden, type-I interferon production, or acquired immunity. In macrophages, Mint3 depletion attenuated NF-κB signalling and the resultant cytokine/chemokine production in response to IFV infection by increasing IκBα and activating the cellular energy sensor AMPK, respectively. Thus, Mint3 might represent one of the likely therapeutic targets for the treatment of severe influenza pneumonia without affecting host anti-viral defence through suppressing macrophage cytokine/chemokine production.",2016 Nov 24,"['Uematsu, Takayuki', 'Fujita, Tomoko', 'Nakaoka, Hiroki J.', 'Hara, Toshiro', 'Kobayashi, Noritada', 'Murakami, Yoshinori', 'Seiki, Motoharu', 'Sakamoto, Takeharu']",Sci Rep,,,True
1c55462ba94ea026e0aef29ad6dbed4520990158,PMC,Mint3/Apba3 depletion ameliorates severe murine influenza pneumonia and macrophage cytokine production in response to the influenza virus,http://dx.doi.org/10.1038/srep37815,PMC5121658,27883071,CC BY,"Influenza virus (IFV) infection is a common cause of severe pneumonia. Studies have suggested that excessive activation of the host immune system including macrophages is responsible for the severe pathologies mediated by IFV infection. Here, we focused on the X11 protein family member Mint3/Apba3, known to promote ATP production via glycolysis by activating hypoxia inducible factor-1 (HIF-1) in macrophages, and examined its roles in lung pathogenesis and anti-viral defence upon IFV infection. Mint3-deficient mice exhibited improved influenza pneumonia with reduced inflammatory cytokines/chemokine levels and neutrophil infiltration in the IFV-infected lungs without alteration in viral burden, type-I interferon production, or acquired immunity. In macrophages, Mint3 depletion attenuated NF-κB signalling and the resultant cytokine/chemokine production in response to IFV infection by increasing IκBα and activating the cellular energy sensor AMPK, respectively. Thus, Mint3 might represent one of the likely therapeutic targets for the treatment of severe influenza pneumonia without affecting host anti-viral defence through suppressing macrophage cytokine/chemokine production.",2016 Nov 24,"['Uematsu, Takayuki', 'Fujita, Tomoko', 'Nakaoka, Hiroki J.', 'Hara, Toshiro', 'Kobayashi, Noritada', 'Murakami, Yoshinori', 'Seiki, Motoharu', 'Sakamoto, Takeharu']",Sci Rep,,,False
784b8019936ae21771682f1184ff3fe10cc40b6f,PMC,The Ebola Outbreak: Catalyzing a “Shift” in Global Health Governance?,http://dx.doi.org/10.1186/s12879-016-2016-y,PMC5121963,27881085,CC BY,"BACKGROUND: As the 2014 Ebola virus disease outbreak (EVD) transitions to its post-endemic phase, its impact on the future of global public health, particularly the World Health Organization (WHO), is the subject of continued debate. Criticism of WHO’s performance grew louder in the outbreak’s wake, placing this international health UN-specialized agency in the difficult position of navigating a complex series of reform recommendations put forth by different stakeholders. Decisions on WHO governance reform and the broader role of the United Nations could very well shape the future landscape of 21st century global health and how the international community responds to health emergencies. DISCUSSION: In order to better understand the implications of the EVD outbreak on global health and infectious disease governance, this debate article critically examines a series of reports issued by four high-level commissions/panels convened to specifically assess WHO’s performance post-Ebola. Collectively, these recommendations add increasing complexity to the urgent need for WHO reform, a process that the agency must carry out in order to maintain its legitimacy. Proposals that garnered strong support included the formation of an independent WHO Centre for Emergency Preparedness and Response, the urgent need to increase WHO infectious disease funding and capacity, and establishing better operational and policy coordination between WHO, UN agencies, and other global health partners. The recommendations also raise more fundamental questions about restructuring the global health architecture, and whether the UN should play a more active role in global health governance. SUMMARY: Despite the need for a fully modernized WHO, reform proposals recently announced by WHO fail to achieve the “evolution” in global health governance needed in order to ensure that global society is adequately protected against the multifaceted and increasingly complex nature of modern public health emergencies. Instead, the lasting legacy of the EVD outbreak may be its foreshadowing of a governance “shift” in formal sharing of the complex responsibilities of global health, health security, outbreak response, and managing health emergencies to other international structures, most notably the United Nations. Only time will tell if the legacy of EVD will include a WHO that has the full support of the international community and is capable of leading human society in this brave new era of the globalization of infectious diseases.",2016 Nov 24,"Mackey, Tim K.",BMC Infect Dis,,,True
b6d7e94615aea8a7a591d68cea8c6710ce86df13,PMC,Anti-tumor effects of Abnormal Savda Munziq on the transplanted cervical cancer (U27) mouse model,http://dx.doi.org/10.1186/s12906-016-1458-5,PMC5122163,27881109,CC BY,"BACKGROUND: Abnormal Savda Munziq (ASMq), a traditional uyghur medicine, has shown anti-tumour properties in vitro. it was showed that total flavonoids of ASMq could inhibit the proliferation and enhance the antioxidant ability of human cervix cancer HeLa cell. This study attempts to confirm these effects on the transplanted cervical cancer (U27) mouse model in vivo. METHODS: Forty eight Kunming mice were randomly divided in to six groups: normal control group (Control group), U27 tumor model group (Model group), cyclophosphamide administration group (CTX group),low-dose ASMq group (ASMq.L group), medium-dose ASMq group (ASMq.M group), and high-dose ASMq group (ASMq.H group). The five groups except normal control group transplanted with cervical cancer (U27) cells. We observed mice tumor inhibition rate and conducted the histopathological analysisUsing the western blot assay, the expression of TGF-β1 and TNF-α protein in transplanted cervical cancer U27 tumor tissue were detected. RESULTS: The tumor inhibition rates of CTX group, ASMq.L group, ASMq.M group, and ASMq.H group were 72.21, 31.27, 60.53 and 51.94% respectively, has obvious antitumor effect. ASMq significantly promote the spleen tlymphocyte proliferation of transplanted cervical cancer U27 mice. Invasive growth and diffusion rate in tumor tissue were accelerate in the transplanted cervical cancer U27 model group. Tumor tissue necrosis of tumor cells are smaller in the medium, high dosage group. Compared with the U27 model group, the expression levels of TGF-β1 protein and TNF-α protein expression exhibited statistically significant decreased in the mice tumor tissues in the CTX administration group and the ASMq administration group. CONCLUSIONS: ASMq has some antitumor effects on U27 model mice in vivo, The effects are achieved not only by improving the immune function of U27 model mice, but also by inhibiting the expression levels of TGF-β1 protein while promoting the expression levels of TNF-α protein.",2016 Nov 24,"['Omarniyaz, Zuhragul', 'Yu, Yang', 'Yang, Tao', 'Shan, Lianlian', 'Miao, Weiwei', 'Reyimu, Renaguli', 'Upur, Halmurat', 'Aikemu, Ainiwaer']",BMC Complement Altern Med,,,True
7d00b513342aa0cdedd01900540fabffe9f54207,PMC,Disinfection of aircraft: Appropriate disinfectants and standard operating procedures for highly infectious diseases,http://dx.doi.org/10.1007/s00103-016-2460-2,PMC5122611,27785522,CC BY,"For infectious diseases caused by highly pathogenic agents (e. g., Ebola/Lassa fever virus, SARS-/MERS-CoV, pandemic influenza virus) which have the potential to spread over several continents within only a few days, international Health Protection Authorities have taken appropriate measures to limit the consequences of a possible spread. A crucial point in this context is the disinfection of an aircraft that had a passenger on board who is suspected of being infected with one of the mentioned diseases. Although, basic advice on hygiene and sanitation on board an aircraft is given by the World Health Organization, these guidelines lack details on available and effective substances as well as standardized operating procedures (SOP). The purpose of this paper is to give guidance on the choice of substances that were tested by a laboratory of Lufthansa Technik and found compatible with aircraft components, as well as to describe procedures which ensure a safe and efficient disinfection of civil aircrafts. This guidance and the additional SOPs are made public and are available as mentioned in this paper.",2016 Oct 26,"['Klaus, Joachim', 'Gnirs, Peter', 'Hölterhoff, Sabine', 'Wirtz, Angela', 'Jeglitza, Matthias', 'Gaber, Walter', 'Gottschalk, Rene']",Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz,,,True
1a485210a47a7eb2d39964a350d68ae52368c1df,PMC,Isolation and characterization of adenoviruses infecting endangered golden snub-nosed monkeys (Rhinopithecus roxellana),http://dx.doi.org/10.1186/s12985-016-0648-6,PMC5123214,27884154,CC BY,"BACKGROUND: Adenoviruses are important pathogens with the potential for interspecies transmission between humans and non-human primates. Although many adenoviruses have been identified in monkeys, the knowledge of these viruses from the Colobinae members is quite limited. FINDINGS: We conducted a surveillance of viral infection in endangered golden snub-nosed monkeys (Rhinopithecus roxellana) in the subfamily Colobinae in China, and found that 5.1% of sampled individuals were positive for adenovirus. One of the adenoviruses (SAdV-WIV19) was successfully isolated and its full-length genome was sequenced. The full-length genome of WIV19 is 33,562 bp in size, has a G + C content of 56.2%, and encodes 35 putative genes. Sequence analysis revealed that this virus represents a novel species in the genus Mastadenovirus. Diverse cell lines, including those of human origin, were susceptible to WIV19. CONCLUSION: We report the first time the isolation and full-length genomic characterization of an adenovirus from the subfamily Colobinae. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0648-6) contains supplementary material, which is available to authorized users.",2016 Nov 25,"['Tan, Bing', 'Wu, Li-Jun', 'Yang, Xing-Lou', 'Li, Bei', 'Zhang, Wei', 'Lei, Yong-Song', 'Li, Yong', 'Yang, Guo-Xiang', 'Chen, Jing', 'Chen, Guang', 'Wang, Han-Zhong', 'Shi, Zheng-Li']",Virol J,,,True
f81a5f06d5cbc6998bddce29a3eb508d8ceb83f7,PMC,Angiotensin-converting enzyme 2 is reduced in Alzheimer’s disease in association with increasing amyloid-β and tau pathology,http://dx.doi.org/10.1186/s13195-016-0217-7,PMC5123239,27884212,CC BY,"BACKGROUND: Hyperactivity of the classical axis of the renin-angiotensin system (RAS), mediated by angiotensin II (Ang II) activation of the angiotensin II type 1 receptor (AT1R), is implicated in the pathogenesis of Alzheimer’s disease (AD). Angiotensin-converting enzyme-2 (ACE-2) degrades Ang II to angiotensin 1–7 (Ang (1-7)) and counter-regulates the classical axis of RAS. We have investigated the expression and distribution of ACE-2 in post-mortem human brain tissue in relation to AD pathology and classical RAS axis activity. METHODS: We measured ACE-2 activity by fluorogenic peptide substrate assay in mid-frontal cortex (Brodmann area 9) in a cohort of AD (n = 90) and age-matched non-demented controls (n = 59) for which we have previous data on ACE-1 activity, amyloid β (Aβ) level and tau pathology, as well as known ACE1 (rs1799752) indel polymorphism, apolipoprotein E (APOE) genotype, and cerebral amyloid angiopathy severity scores. RESULTS: ACE-2 activity was significantly reduced in AD compared with age-matched controls (P < 0.0001) and correlated inversely with levels of Aβ (r = −0.267, P < 0.001) and phosphorylated tau (p-tau) pathology (r = −0.327, P < 0.01). ACE-2 was reduced in individuals possessing an APOE ε4 allele (P < 0.05) and was associated with ACE1 indel polymorphism (P < 0.05), with lower ACE-2 activity in individuals homozygous for the ACE1 insertion AD risk allele. ACE-2 activity correlated inversely with ACE-1 activity (r = −0.453, P < 0.0001), and the ratio of ACE-1 to ACE-2 was significantly elevated in AD (P < 0.0001). Finally, we show that the ratio of Ang II to Ang (1–7) (a proxy measure of ACE-2 activity indicating conversion of Ang II to Ang (1–7)) is reduced in AD. CONCLUSIONS: Together, our findings indicate that ACE-2 activity is reduced in AD and is an important regulator of the central classical ACE-1/Ang II/AT1R axis of RAS, and also that dysregulation of this pathway likely plays a significant role in the pathogenesis of AD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-016-0217-7) contains supplementary material, which is available to authorized users.",2016 Nov 25,"['Kehoe, Patrick Gavin', 'Wong, Steffenny', 'AL Mulhim, Noura', 'Palmer, Laura Elyse', 'Miners, J. Scott']",Alzheimers Res Ther,,,True
3c082fd7a87e4e55f001e749fa9ce2a3481b0f5f,PMC,A bibliometric analysis of literature on malaria vector resistance: (1996 – 2015),http://dx.doi.org/10.1186/s12992-016-0214-4,PMC5123357,27884199,CC BY,"BACKGROUND: Emergence of insecticide resistance in malaria vectors is a real threat to future goals of elimination and control of malaria. Therefore, the objective of this study was to assess research trend on insecticide resistance of Anopheles mosquito. In specific, number of publications, countries, institutions, and authors’ research profile, citation analysis, international collaborations, and impact of journals publishing documents on insecticide resistance will be presented. It was conducted via Scopus search engine which was used to retrieve relevant data. Keywords used were based on literature available on this topic. The duration of study was set from 1996–2015. RESULTS: A total of 616 documents, mainly as original research articles (n = 569; 92.37%) were retrieved. The average number of citations per article was 26.36. Poisson log-linear regression analysis indicated that there was a 6.00% increase in the number of publications for each extra article on pyrethroid resistance. A total of 82 different countries and 1922 authors participated in publishing retrieved articles. The United Kingdom (UK) ranked first in number of publications followed by the United States of America (USA) and France. The top ten productive countries included seven African countries. The UK had collaborations mostly with Benin (relative link strength = 46). A total of 1817 institution/ organizations participated in the publication of retrieved articles. The most active institution/ organization was Liverpool School of Tropical Medicine. Retrieved articles were published in 134 different scientific peer reviewed journals. The journal that published most on this topic was Malaria Journal (n = 101; 16.4%). Four of the top active authors were from South Africa and two were from the UK. Three of the top ten cited articles were published in Insect Molecular Biology journal. Six articles were about pyrethroid resistance and at least two were about DDT resistance. CONCLUSION: Publications on insecticide resistance in malaria vector has gained momentum in the past decade. International collaborations enhanced the knowledge about the situation of vector resistance in countries with endemic malaria. Molecular biology of insecticide resistance is the key issue in understanding and overcoming this emerging problems.",2016 Nov 25,"['Sweileh, Waleed M.', 'Sawalha, Ansam F.', 'Al-Jabi, Samah W.', 'Zyoud, Sa’ed H.', 'Shraim, Naser Y.', 'Abu-Taha, Adham S.']",Global Health,,,True
1ef187d95b5c98c9ef187f3b5cf23e276bf1b018,PMC,Detection and phylogenetic analysis of porcine epidemic diarrhea virus in central China based on the ORF3 gene and the S1 gene,http://dx.doi.org/10.1186/s12985-016-0646-8,PMC5123408,27887624,CC BY,"BACKGROUND: Porcine epidemic diarrhea (PED) has increased in severity in China since 2010. To investigate further the infectivity, genetic diversity and molecular epidemiology of its causative agent, the porcine epidemic diarrhea virus (PEDV), we assessed 129 clinical samples, which were the intestinal tissue of piglets with severe diarrhea, from 17 cities in central China. Both the spike (S) glycoprotein (S1, 1–789 amino acids (aa)) and the full-length ORF3 gene of 21 representative field strains from 21 farms in 11 cities were sequenced and analysed. METHODS: PEDV was detected by reverse transcription-polymerase chain reaction (RT-PCR), and S1 and ORF3 sequences were processed by the Clustal W method via DNAMAN 8 software, and phylogenetic trees were constructed by the neighbor-joining method using MEGA 6 software. RESULTS: The prevalence of PEDV was 92.25% and was detected in 119 of 129 samples, with 94.03% (63 of 67) of pig farms harbouring the disease. According to the phylogenetic analysis of the S1 genes, our isolates all fell into group G2 (variants) and showed a close relationship to isolates from Chinese (HN1303, CH/ZMDZY/11 and AJ1102), Korean (AD01), American (MN, IA1, IA2 and 13–019349) sources, and these isolates differed genetically from other Chinese (LZC, CH/HNZZ/2011 and SD-M) and Korean (SM98) strains as well Japanese (83-P5 and MK) strains. In addition, our isolates differed from attenuated vaccine strains, CV777 (used in China) and DR13 (used in Korea). According to our derived amino acid sequence analysis, we detected one novel variant PEDV, viz: CH/HNLY, with 4-aa insertion/deletion (RSSS/T) at position 375 and 1-aa (D) deletion at position 430 compared to the CV777 attenuated strain. These mutations were located on the receptor binding domain. Our ORF3 gene analyses showed that the prevalent PEDV isolates were variants, and the isolated strains differed genetically from the vaccine strains. CONCLUSIONS: These findings illustrated the existence of genetic diversity among geographically distinct PEDV strains, and our study has provided an impetus to conduct further research on the PEDV receptor binding protein and on the new and efficacious vaccines design. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0646-8) contains supplementary material, which is available to authorized users.",2016 Nov 25,"['Su, Yunfang', 'Liu, Yunchao', 'Chen, Yumei', 'Zhao, Baolei', 'Ji, Pengchao', 'Xing, Guangxu', 'Jiang, Dawei', 'Liu, Chang', 'Song, Yapeng', 'Wang, Guoqiang', 'Li, Dongliang', 'Deng, Ruiguang', 'Zhang, Gaiping']",Virol J,,,True
c7d52191db94d11ad1d56bb48ecc64656b44a613,PMC,"In the eye of the beholder: to make global health estimates useful, make them more socially robust",http://dx.doi.org/10.3402/gha.v9.32298,PMC5124117,28532303,CC BY,"A plethora of new development goals and funding institutions have greatly increased the demand for internationally comparable health estimates in recent years, and have brought important new players into the field of health estimate production. These changes have rekindled debates about the validity and legitimacy of global health estimates. This paper draws on country case studies and personal experience to support our opinion that the production and use of estimates are deeply embedded in specific social, economic, political and ideational contexts, which differ at different levels of the global health architecture. Broadly, most global health estimates tend to be made far from the local contexts in which the data upon which they are based are collected, and where the results of estimation processes must ultimately be used if they are to make a difference to the health of individuals. Internationally standardised indicators are necessary, but they are no substitute for data that meet local needs, and that fit with local ideas of what is credible and useful. In other words, data that are both technically and socially robust for those who make key decisions about health. We suggest that greater engagement of local actors (and local data) in the formulation, communication and interpretation of health estimates would increase the likelihood that these data will be used by those most able to translate them into health gains for the longer term. Besides strengthening national information systems, this requires ongoing interaction, building trust and establishing a communicative infrastructure. Local capacities to use knowledge to improve health must be supported.",2017 May 22,"['Pisani, Elizabeth', 'Kok, Maarten']",Glob Health Action,,,True
dd94afcee3d0c4dbc80b40435ff4fb65487af3b6,PMC,The performance of interferon-gamma release assay in nontuberculous mycobacterial diseases: a retrospective study in China,http://dx.doi.org/10.1186/s12890-016-0320-3,PMC5124224,27887611,CC BY,"BACKGROUND: The interferon-gamma release assay (IGRA) is more specific than the tuberculin skin test to discriminate between tuberculosis (TB) and nontuberculous mycobacterial (NTM) diseases. Here we performed a retrospective study to evaluate the performance of the T-SPOT.TB in patients with NTM diseases. METHODS: Between March, 2013 and Nov, 2015, a total of 58 patients with NTM diseases had a T-SPOT.TB performed were enrolled, 30 patients had definite NTM diseases, 28 had probable diseases. Their clinicopathological characteristics were reviewed and analyzed. Cultures for mycobacteria were performed. The indirect proportion method with Löwenstein–Jensen (L-J) medium was used for first-line drug susceptibility test. T-SPOT.TB assay was performed according to the manufacturer’s instructions. Data were expressed as mean ± standard deviation (continuous variables) and as numbers and percentages (categorical variables). The χ (2) test was used for comparisons between proportions. RESULTS: The average age was 51.8 ± 16.1 years (range 10 to 77 years), 58.6% (34/58) were male. 16.4% (9/55) were TB-PCR positive. 34 (58.6%) isolates were Mycobacterium intracellulare, ten (17.2%) were Mycobacterium chelonae and seven (12.1%) were Mycobacterium fortuitum. Fifty-two (89.7%) patients were NTM lung disease, five (8.6%) were pleural disease, and one (1.7%) lymphadenitis. The total positivity of T-SPOT.TB was 53.4% (31/58) among the whole group (probable and definite). For probable cases, the T-SPOT.TB assay was positive in 53.5% (15/28); for definite cases, 16 (53.3%) of 30 definite cases were positive. There was no statistical difference in the positivity rate between them (P < 0.01). CONCLUSIONS: In the study, we showed that a significant portion of NTM diseases were T-SPOT.TB positive in China. Although T-SPOT.TB is useful diagnostic method for differentiating TB from NTM diseases, in China, the IGRA assay show limited value in the discrimination. In addition, further research is needed to investigate the association between TB infection and treatment for NTM patients.",2016 Nov 25,"['Wang, Mao-Shui', 'Wang, Jun-Li', 'Wang, Xin-Feng']",BMC Pulm Med,,,True
48aba0f18c129840aeb900f176b1f40de0b598a4,PMC,Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune potential against H5N1 influenza virus,http://dx.doi.org/10.1038/srep37915,PMC5124960,27892498,CC BY,"H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.",2016 Nov 28,"['Yasui, Fumihiko', 'Itoh, Yasushi', 'Ikejiri, Ai', 'Kitabatake, Masahiro', 'Sakaguchi, Nobuo', 'Munekata, Keisuke', 'Shichinohe, Shintaro', 'Hayashi, Yukiko', 'Ishigaki, Hirohito', 'Nakayama, Misako', 'Sakoda, Yoshihiro', 'Kida, Hiroshi', 'Ogasawara, Kazumasa', 'Kohara, Michinori']",Sci Rep,,,True
6288976f9f6047712e54ceada28a66fdeed771ab,PMC,Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune potential against H5N1 influenza virus,http://dx.doi.org/10.1038/srep37915,PMC5124960,27892498,CC BY,"H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.",2016 Nov 28,"['Yasui, Fumihiko', 'Itoh, Yasushi', 'Ikejiri, Ai', 'Kitabatake, Masahiro', 'Sakaguchi, Nobuo', 'Munekata, Keisuke', 'Shichinohe, Shintaro', 'Hayashi, Yukiko', 'Ishigaki, Hirohito', 'Nakayama, Misako', 'Sakoda, Yoshihiro', 'Kida, Hiroshi', 'Ogasawara, Kazumasa', 'Kohara, Michinori']",Sci Rep,,,False
ddfd6e95ebc735146d0f0d6ea7faacaf99d9613c,PMC,SARS-CoV fusion peptides induce membrane surface ordering and curvature,http://dx.doi.org/10.1038/srep37131,PMC5125003,27892522,CC BY,"Viral membrane fusion is an orchestrated process triggered by membrane-anchored viral fusion glycoproteins. The S2 subunit of the spike glycoprotein from severe acute respiratory syndrome (SARS) coronavirus (CoV) contains internal domains called fusion peptides (FP) that play essential roles in virus entry. Although membrane fusion has been broadly studied, there are still major gaps in the molecular details of lipid rearrangements in the bilayer during fusion peptide-membrane interactions. Here we employed differential scanning calorimetry (DSC) and electron spin resonance (ESR) to gather information on the membrane fusion mechanism promoted by two putative SARS FPs. DSC data showed the peptides strongly perturb the structural integrity of anionic vesicles and support the hypothesis that the peptides generate opposing curvature stresses on phosphatidylethanolamine membranes. ESR showed that both FPs increase lipid packing and head group ordering as well as reduce the intramembrane water content for anionic membranes. Therefore, bending moment in the bilayer could be generated, promoting negative curvature. The significance of the ordering effect, membrane dehydration, changes in the curvature properties and the possible role of negatively charged phospholipids in helping to overcome the high kinetic barrier involved in the different stages of the SARS-CoV-mediated membrane fusion are discussed.",2016 Nov 28,"['Basso, Luis G. M.', 'Vicente, Eduardo F.', 'Crusca Jr., Edson', 'Cilli, Eduardo M.', 'Costa-Filho, Antonio J.']",Sci Rep,,,True
c182fa44ed42d3f4bce316dc78bec2ea3b6d31ba,PMC,Analysis of Synonymous Codon Usage Bias of Zika Virus and Its Adaption to the Hosts,http://dx.doi.org/10.1371/journal.pone.0166260,PMC5125587,27893824,CC BY,"Zika virus (ZIKV) is a mosquito-borne virus (arbovirus) in the family Flaviviridae, and the symptoms caused by ZIKV infection in humans include rash, fever, arthralgia, myalgia, asthenia and conjunctivitis. Codon usage bias analysis can reveal much about the molecular evolution and host adaption of ZIKV. To gain insight into the evolutionary characteristics of ZIKV, we performed a comprehensive analysis on the codon usage pattern in 46 ZIKV strains by calculating the effective number of codons (ENc), codon adaptation index (CAI), relative synonymous codon usage (RSCU), and other indicators. The results indicate that the codon usage bias of ZIKV is relatively low. Several lines of evidence support the hypothesis that translational selection plays a role in shaping the codon usage pattern of ZIKV. The results from a correspondence analysis (CA) indicate that other factors, such as base composition, aromaticity, and hydrophobicity may also be involved in shaping the codon usage pattern of ZIKV. Additionally, the results from a comparative analysis of RSCU between ZIKV and its hosts suggest that ZIKV tends to evolve codon usage patterns that are comparable to those of its hosts. Moreover, selection pressure from Homo sapiens on the ZIKV RSCU patterns was found to be dominant compared with that from Aedes aegypti and Aedes albopictus. Taken together, both natural translational selection and mutation pressure are important for shaping the codon usage pattern of ZIKV. Our findings contribute to understanding the evolution of ZIKV and its adaption to its hosts.",2016 Nov 28,"['Wang, Hongju', 'Liu, Siqing', 'Zhang, Bo', 'Wei, Wenqiang']",PLoS One,,,True
1fddc1d4d4d31015df5e948d0119947b8bd681d1,PMC,Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection,http://dx.doi.org/10.1371/journal.pone.0167221,PMC5125695,27893810,CC BY,"Influenza A virus (IAV) causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection.",2016 Nov 28,"['Perwitasari, Olivia', 'Johnson, Scott', 'Yan, Xiuzhen', 'Register, Emery', 'Crabtree, Jackelyn', 'Gabbard, Jon', 'Howerth, Elizabeth', 'Shacham, Sharon', 'Carlson, Robert', 'Tamir, Sharon', 'Tripp, Ralph A.']",PLoS One,,,True
fbf232152712b5e379797c6b0008bb7926001bb7,PMC,Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells,http://dx.doi.org/10.1038/srep38115,PMC5126690,27897259,CC BY,"SM934 is an artemisinin analogue with immunosuppressive properties and potent therapeutic activity against lupus-like diseases in autoimmune mice. In this report, the therapeutic efficacy and underlying mechanisms of SM934 on rheumatoid arthritis (RA) was investigated using collagen-induced arthritis (CIA) in DBA/1J mice. We demonstrated that SM934 treatment alleviate the severity of arthritis in CIA mice with established manifestations. The therapeutic benefits were associated with ameliorated joint swelling and reduced extent of bone erosion and destruction. Further, administration of SM934 diminished the development of T follicular helper (Tfh) cells and Th17 cells and suppressed the production of pathogenic antibodies, without altering the proportion of germinal center B cells. Ex vivo, SM934 treatment inhibited the bovine type II collagen (CII) induced proliferation and inflammatory cytokines secretion of CII -reactive T cells. In vitro, SM934 impeded the polarization of naïve CD4(+) T cells into Tfh cells and the expression of its transcript factor Bcl-6. Moreover, SM934 decreased the IL-21-producing CD4(+) T cells and dampened the IL-21 downstream signaling through STAT3. These finding offered the convincing evidence that artemisinin derivative might attenuate RA by simultaneously interfering with the generation of Tfh cells and Th17 cells as well as the subsequent antibody-mediated immune responses.",2016 Nov 29,"['Lin, Ze-Min', 'Yang, Xiao-Qian', 'Zhu, Feng-Hua', 'He, Shi-Jun', 'Tang, Wei', 'Zuo, Jian-Ping']",Sci Rep,,,True
b706357b278bc457986d817617d68ea75f10dda7,PMC,Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells,http://dx.doi.org/10.1038/srep38115,PMC5126690,27897259,CC BY,"SM934 is an artemisinin analogue with immunosuppressive properties and potent therapeutic activity against lupus-like diseases in autoimmune mice. In this report, the therapeutic efficacy and underlying mechanisms of SM934 on rheumatoid arthritis (RA) was investigated using collagen-induced arthritis (CIA) in DBA/1J mice. We demonstrated that SM934 treatment alleviate the severity of arthritis in CIA mice with established manifestations. The therapeutic benefits were associated with ameliorated joint swelling and reduced extent of bone erosion and destruction. Further, administration of SM934 diminished the development of T follicular helper (Tfh) cells and Th17 cells and suppressed the production of pathogenic antibodies, without altering the proportion of germinal center B cells. Ex vivo, SM934 treatment inhibited the bovine type II collagen (CII) induced proliferation and inflammatory cytokines secretion of CII -reactive T cells. In vitro, SM934 impeded the polarization of naïve CD4(+) T cells into Tfh cells and the expression of its transcript factor Bcl-6. Moreover, SM934 decreased the IL-21-producing CD4(+) T cells and dampened the IL-21 downstream signaling through STAT3. These finding offered the convincing evidence that artemisinin derivative might attenuate RA by simultaneously interfering with the generation of Tfh cells and Th17 cells as well as the subsequent antibody-mediated immune responses.",2016 Nov 29,"['Lin, Ze-Min', 'Yang, Xiao-Qian', 'Zhu, Feng-Hua', 'He, Shi-Jun', 'Tang, Wei', 'Zuo, Jian-Ping']",Sci Rep,,,False
9cda807f855a7d3786031858813d285ab5a81474,PMC,Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells,http://dx.doi.org/10.1038/srep38115,PMC5126690,27897259,CC BY,"SM934 is an artemisinin analogue with immunosuppressive properties and potent therapeutic activity against lupus-like diseases in autoimmune mice. In this report, the therapeutic efficacy and underlying mechanisms of SM934 on rheumatoid arthritis (RA) was investigated using collagen-induced arthritis (CIA) in DBA/1J mice. We demonstrated that SM934 treatment alleviate the severity of arthritis in CIA mice with established manifestations. The therapeutic benefits were associated with ameliorated joint swelling and reduced extent of bone erosion and destruction. Further, administration of SM934 diminished the development of T follicular helper (Tfh) cells and Th17 cells and suppressed the production of pathogenic antibodies, without altering the proportion of germinal center B cells. Ex vivo, SM934 treatment inhibited the bovine type II collagen (CII) induced proliferation and inflammatory cytokines secretion of CII -reactive T cells. In vitro, SM934 impeded the polarization of naïve CD4(+) T cells into Tfh cells and the expression of its transcript factor Bcl-6. Moreover, SM934 decreased the IL-21-producing CD4(+) T cells and dampened the IL-21 downstream signaling through STAT3. These finding offered the convincing evidence that artemisinin derivative might attenuate RA by simultaneously interfering with the generation of Tfh cells and Th17 cells as well as the subsequent antibody-mediated immune responses.",2016 Nov 29,"['Lin, Ze-Min', 'Yang, Xiao-Qian', 'Zhu, Feng-Hua', 'He, Shi-Jun', 'Tang, Wei', 'Zuo, Jian-Ping']",Sci Rep,,,False
38b50147abf86a5818c6bb5e09b1f07edf51352b,PMC,Antiviral Screening of Multiple Compounds against Ebola Virus,http://dx.doi.org/10.3390/v8110277,PMC5127007,27801778,CC BY,"In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine). A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna). The three most promising compounds (17-DMAG; BGB324; and NCK-8) were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.",2016 Oct 27,"['Dowall, Stuart D.', 'Bewley, Kevin', 'Watson, Robert J.', 'Vasan, Seshadri S.', 'Ghosh, Chandradhish', 'Konai, Mohini M.', 'Gausdal, Gro', 'Lorens, James B.', 'Long, Jason', 'Barclay, Wendy', 'Garcia-Dorival, Isabel', 'Hiscox, Julian', 'Bosworth, Andrew', 'Taylor, Irene', 'Easterbrook, Linda', 'Pitman, James', 'Summers, Sian', 'Chan-Pensley, Jenny', 'Funnell, Simon', 'Vipond, Julia', 'Charlton, Sue', 'Haldar, Jayanta', 'Hewson, Roger', 'Carroll, Miles W.']",Viruses,,,True
4abc50cfc81265083d4cb2aed0a493bb704d0b5b,PMC,Rabies Control and Treatment: From Prophylaxis to Strategies with Curative Potential,http://dx.doi.org/10.3390/v8110279,PMC5127009,27801824,CC BY,"Rabies is an acute, fatal, neurological disease that affects almost all kinds of mammals. Vaccination (using an inactivated rabies vaccine), combined with administration of rabies immune globulin, is the only approved, effective method for post-exposure prophylaxis against rabies in humans. In the search for novel rabies control and treatment strategies, live-attenuated viruses have recently emerged as a practical and promising approach for immunizing and controlling rabies. Unlike the conventional, inactivated rabies vaccine, live-attenuated viruses are genetically modified viruses that are able to replicate in an inoculated recipient without causing adverse effects, while still eliciting robust and effective immune responses against rabies virus infection. A number of viruses with an intrinsic capacity that could be used as putative candidates for live-attenuated rabies vaccine have been intensively evaluated for therapeutic purposes. Additional novel strategies, such as a monoclonal antibody-based approach, nucleic acid-based vaccines, or small interfering RNAs (siRNAs) interfering with virus replication, could further add to the arena of strategies to combat rabies. In this review, we highlight current advances in rabies therapy and discuss the role that they might have in the future of rabies treatment. Given the pronounced and complex impact of rabies on a patient, a combination of these novel modalities has the potential to achieve maximal anti-rabies efficacy, or may even have promising curative effects in the future. However, several hurdles regarding clinical safety considerations and public awareness should be overcome before these approaches can ultimately become clinically relevant therapies.",2016 Oct 28,"['Zhu, Shimao', 'Guo, Caiping']",Viruses,,,True
bf2609459ed9b514ad4b6ee4b0eb3656c0d6542d,PMC,The Importance of Physiologically Relevant Cell Lines for Studying Virus–Host Interactions,http://dx.doi.org/10.3390/v8110297,PMC5127011,27809273,CC BY,"Viruses interact intimately with the host cell at nearly every stage of replication, and the cell model that is chosen to study virus infection is critically important. Although primary cells reflect the phenotype of healthy cells in vivo better than cell lines, their limited lifespan makes experimental manipulation challenging. However, many tumor-derived and artificially immortalized cell lines have defects in induction of interferon-stimulated genes and other antiviral defenses. These defects can affect virus replication, especially when cells are infected at lower, more physiologically relevant, multiplicities of infection. Understanding the selective pressures and mechanisms underlying the loss of innate signaling pathways is helpful to choose immortalized cell lines without impaired antiviral defense. We describe the trials and tribulations we encountered while searching for an immortalized cell line with intact innate signaling, and how directed immortalization of primary cells avoids many of the pitfalls of spontaneous immortalization.",2016 Nov 1,"['Hare, David', 'Collins, Susan', 'Cuddington, Breanne', 'Mossman, Karen']",Viruses,,,True
ae918e83ef815351c2c0e47a337ec78954f5cec0,PMC,The European Classical Swine Fever Virus Database: Blueprint for a Pathogen-Specific Sequence Database with Integrated Sequence Analysis Tools,http://dx.doi.org/10.3390/v8110302,PMC5127016,27827988,CC BY,"Molecular epidemiology has become an indispensable tool in the diagnosis of diseases and in tracing the infection routes of pathogens. Due to advances in conventional sequencing and the development of high throughput technologies, the field of sequence determination is in the process of being revolutionized. Platforms for sharing sequence information and providing standardized tools for phylogenetic analyses are becoming increasingly important. The database (DB) of the European Union (EU) and World Organisation for Animal Health (OIE) Reference Laboratory for classical swine fever offers one of the world’s largest semi-public virus-specific sequence collections combined with a module for phylogenetic analysis. The classical swine fever (CSF) DB (CSF-DB) became a valuable tool for supporting diagnosis and epidemiological investigations of this highly contagious disease in pigs with high socio-economic impacts worldwide. The DB has been re-designed and now allows for the storage and analysis of traditionally used, well established genomic regions and of larger genomic regions including complete viral genomes. We present an application example for the analysis of highly similar viral sequences obtained in an endemic disease situation and introduce the new geographic “CSF Maps” tool. The concept of this standardized and easy-to-use DB with an integrated genetic typing module is suited to serve as a blueprint for similar platforms for other human or animal viruses.",2016 Nov 7,"['Postel, Alexander', 'Schmeiser, Stefanie', 'Zimmermann, Bernd', 'Becher, Paul']",Viruses,,,True
d2d8597279c4e4503fbe1c11365fd154230add81,PMC,Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions,http://dx.doi.org/10.3390/v8110304,PMC5127018,27834891,CC BY,"The key to better understanding complex virus-host interactions is the utilization of robust three-dimensional (3D) human cell cultures that effectively recapitulate native tissue architecture and model the microenvironment. A lack of physiologically-relevant animal models for many viruses has limited the elucidation of factors that influence viral pathogenesis and of complex host immune mechanisms. Conventional monolayer cell cultures may support viral infection, but are unable to form the tissue structures and complex microenvironments that mimic host physiology and, therefore, limiting their translational utility. The rotating wall vessel (RWV) bioreactor was designed by the National Aeronautics and Space Administration (NASA) to model microgravity and was later found to more accurately reproduce features of human tissue in vivo. Cells grown in RWV bioreactors develop in a low fluid-shear environment, which enables cells to form complex 3D tissue-like aggregates. A wide variety of human tissues (from neuronal to vaginal tissue) have been grown in RWV bioreactors and have been shown to support productive viral infection and physiological meaningful host responses. The in vivo-like characteristics and cellular features of the human 3D RWV-derived aggregates make them ideal model systems to effectively recapitulate pathophysiology and host responses necessary to conduct rigorous basic science, preclinical and translational studies.",2016 Nov 9,"['Gardner, Jameson K.', 'Herbst-Kralovetz, Melissa M.']",Viruses,,,True
450c84277f6e9475368ad36719ef5d7b6595b514,PMC,Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses,http://dx.doi.org/10.3390/v8110311,PMC5127025,27869695,CC BY,"Griffithsin (GRFT), a lectin from Griffithsia species, inhibits human immunodeficiency virus-1 (HIV-1) replication at sub-nanomolar concentrations, with limited cellular toxicity. However, in vivo safety of GRFT is not fully understood, especially following parenteral administration. We first assessed GRFT’s effects in vitro, on mouse peripheral blood mononuclear cell (mPBMC) viability, mitogenicity, and activation using flow-cytometry, as well as cytokine secretion through enzyme-linked immunosorbent assay (ELISA). Toxicological properties of GRFT were determined after a single subcutaneous administration of 50 mg/kg or 14 daily doses of 10 mg/kg in BALB/c mice. In the context of microbicide development, toxicity of GRFT at 2 mg/kg was determined after subcutaneous, intravaginal, and intraperitoneal administrations, respectively. Interestingly, GRFT caused no significant cell death, mitogenicity, activation, or cytokine release in mPBMCs, validating the usefulness of a mouse model. An excellent safety profile for GRFT was obtained in vivo: no overt changes were observed in animal fitness, blood chemistry or CBC parameters. Following GRFT treatment, reversible splenomegaly was observed with activation of certain spleen B and T cells. However, spleen tissues were not pathologically altered by GRFT (either with a single high dose or chronic doses). Finally, no detectable toxicity was found after mucosal or systemic treatment with 2 mg/kg GRFT, which should be further developed as a microbicide for HIV prevention.",2016 Nov 17,"['Kouokam, Joseph Calvin', 'Lasnik, Amanda B.', 'Palmer, Kenneth E.']",Viruses,,,True
cc162db1b7050ca10b6b99bf2857185777acb67b,PMC,Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses,http://dx.doi.org/10.3390/v8110311,PMC5127025,27869695,CC BY,"Griffithsin (GRFT), a lectin from Griffithsia species, inhibits human immunodeficiency virus-1 (HIV-1) replication at sub-nanomolar concentrations, with limited cellular toxicity. However, in vivo safety of GRFT is not fully understood, especially following parenteral administration. We first assessed GRFT’s effects in vitro, on mouse peripheral blood mononuclear cell (mPBMC) viability, mitogenicity, and activation using flow-cytometry, as well as cytokine secretion through enzyme-linked immunosorbent assay (ELISA). Toxicological properties of GRFT were determined after a single subcutaneous administration of 50 mg/kg or 14 daily doses of 10 mg/kg in BALB/c mice. In the context of microbicide development, toxicity of GRFT at 2 mg/kg was determined after subcutaneous, intravaginal, and intraperitoneal administrations, respectively. Interestingly, GRFT caused no significant cell death, mitogenicity, activation, or cytokine release in mPBMCs, validating the usefulness of a mouse model. An excellent safety profile for GRFT was obtained in vivo: no overt changes were observed in animal fitness, blood chemistry or CBC parameters. Following GRFT treatment, reversible splenomegaly was observed with activation of certain spleen B and T cells. However, spleen tissues were not pathologically altered by GRFT (either with a single high dose or chronic doses). Finally, no detectable toxicity was found after mucosal or systemic treatment with 2 mg/kg GRFT, which should be further developed as a microbicide for HIV prevention.",2016 Nov 17,"['Kouokam, Joseph Calvin', 'Lasnik, Amanda B.', 'Palmer, Kenneth E.']",Viruses,,,False
dbd7344969972f79b75ee7553487633e645d9a3b,PMC,Towards Equity in Health: Researchers Take Stock,http://dx.doi.org/10.1371/journal.pmed.1002186,PMC5127492,27898673,CC0,"For the 2016 end-of-the-year editorial, the PLOS Medicine editors asked 7 global health leaders to discuss developments relevant to the equitable provision of medical care to all populations. The result is a collection of expert views on ethical trial design, research during outbreaks, high-burden infectious diseases, diversity in research and protection of migrants.",2016 Nov 29,"[None, 'Rid, Annette', 'Johansson, Michael A.', 'Leung, Gabriel', 'Valantine, Hannah', 'Burchard, Esteban G.', 'Oh, Sam S.', 'Zimmerman, Cathy']",PLoS Med,,,True
89444dffc7f46f0f52709e43550ddb363a720340,PMC,Analysis of chikungunya virus proteins reveals that non-structural proteins nsP2 and nsP3 exhibit RNA interference (RNAi) suppressor activity,http://dx.doi.org/10.1038/srep38065,PMC5128919,27901124,CC BY,"RNAi pathway is an antiviral defence mechanism employed by insects that result in degradation of viral RNA thereby curbing infection. Several viruses including flaviviruses encode viral suppressors of RNAi (VSRs) to counteract the antiviral RNAi pathway. Till date, no VSR has been reported in alphaviruses. The present study was undertaken to evaluate chikungunya virus (CHIKV) proteins for RNAi suppressor activity. We systematically analyzed all nine CHIKV proteins for RNAi suppressor activity using Sf21 RNAi sensor cell line based assay. Two non-structural proteins, namely, nsP2 and nsP3 were found to exhibit RNAi suppressor activity. We further validated the findings in natural hosts, namely in Aedes and in mammalian cell lines and further through EMSA and Agrobacterium infiltration in GFP silenced transgenic tobacco plants. Domains responsible for maximum RNAi suppressor activity were also identified within these proteins. RNA binding motifs in these domains were identified and their participation in RNAi suppression evaluated using site directed mutagenesis. Sequence alignment of these motifs across all species of known alphaviruses revealed conservation of these motifs emphasizing on a similar role of action in other species of alphaviruses as well. Further validation of RNAi suppressor activity of these proteins awaits establishment of specific virus infection models.",2016 Nov 30,"['Mathur, Kalika', 'Anand, Abhishek', 'Dubey, Sunil Kumar', 'Sanan-Mishra, Neeti', 'Bhatnagar, Raj K.', 'Sunil, Sujatha']",Sci Rep,,,True
64bdff3b452cc5f83921b0e3811d4be1cf1af3cf,PMC,Analysis of chikungunya virus proteins reveals that non-structural proteins nsP2 and nsP3 exhibit RNA interference (RNAi) suppressor activity,http://dx.doi.org/10.1038/srep38065,PMC5128919,27901124,CC BY,"RNAi pathway is an antiviral defence mechanism employed by insects that result in degradation of viral RNA thereby curbing infection. Several viruses including flaviviruses encode viral suppressors of RNAi (VSRs) to counteract the antiviral RNAi pathway. Till date, no VSR has been reported in alphaviruses. The present study was undertaken to evaluate chikungunya virus (CHIKV) proteins for RNAi suppressor activity. We systematically analyzed all nine CHIKV proteins for RNAi suppressor activity using Sf21 RNAi sensor cell line based assay. Two non-structural proteins, namely, nsP2 and nsP3 were found to exhibit RNAi suppressor activity. We further validated the findings in natural hosts, namely in Aedes and in mammalian cell lines and further through EMSA and Agrobacterium infiltration in GFP silenced transgenic tobacco plants. Domains responsible for maximum RNAi suppressor activity were also identified within these proteins. RNA binding motifs in these domains were identified and their participation in RNAi suppression evaluated using site directed mutagenesis. Sequence alignment of these motifs across all species of known alphaviruses revealed conservation of these motifs emphasizing on a similar role of action in other species of alphaviruses as well. Further validation of RNAi suppressor activity of these proteins awaits establishment of specific virus infection models.",2016 Nov 30,"['Mathur, Kalika', 'Anand, Abhishek', 'Dubey, Sunil Kumar', 'Sanan-Mishra, Neeti', 'Bhatnagar, Raj K.', 'Sunil, Sujatha']",Sci Rep,,,False
59e5392ae9728ae529623e00c6d2e411a931fffc,PMC,Having a usual source of care and its associated factors in Korean adults: a cross-sectional study of the 2012 Korea Health Panel Survey,http://dx.doi.org/10.1186/s12875-016-0555-3,PMC5129206,27899071,CC BY,"BACKGROUND: Usual source of care (USC) is one of the hallmarks of primary care. We aimed to examine the status of having a USC and its patient-related sociodemographic factors among Korean adults. METHODS: Data were obtained from the 2012 Korea Health Panel survey. Panel participants were selected for the study who were aged 18 years or older and who replied to questionnaire items on having a USC (n = 11,935). RESULTS: Of the participants, 21.5% had a usual place and 13.9% had a usual physician. Reasons for not having a USC were seldom being ill (66.1%), the preference to visit multiple medical institutions (27.9%), and others. The private community clinic was the most common type of usual place (57.0%). In patient-reported attributes of care provided by a usual physician, the percentages of positive responses for comprehensiveness and coordination were 67.2% and 34.5%, respectively. By institution type, primary care clinics showed the lowest percentage (32.8%) of positive responses for coordination. Adjusted odds ratios of having a usual physician were 3.77 (95% confidence interval, CI: 3.75–3.79) for those aged 65 years or older (vs. aged 18–34 years), 1.31 (CI: 1.30–1.31) for females (vs. males), 0.72 (CI: 0.72–0.73) for unmarried people (vs. married), 1.16 (CI: 1.16–1.16) for college graduates or higher (vs. elementary school graduate or less), 0.64 for the fifth quintile (vs. the first quintile) by household income, 1.53 (CI: 1.52–1.54) for Medical Aid (vs. employee health insurance) for type of health insurance, and 4.09 (CI: 4.08–4.10) for presence (vs. absence) of a chronic diseases. CONCLUSIONS: The proportion of Korean adults who have a USC is extremely low, the most influential factor of having a USC is having a chronic disease or not, and Korean patients experience much poorer health care coordination than do patients in other industrialized countries. The findings of this study will give insight to researchers and policy makers regarding the potential facilitators of and barriers to promoting having a USC in the general Korean public.",2016 Nov 29,"['An, Ah Reum', 'Kim, Kyoungwoo', 'Lee, Jae-Ho', 'Sung, Nak-Jin', 'Lee, Sang-il', 'Hyun, Min Kyung']",BMC Fam Pract,,,True
7729f9d0b2d49fd43519f42d2637a55b03e1c778,PMC,Multiple molecular detection of respiratory viruses and associated signs of airway inflammation in racehorses,http://dx.doi.org/10.1186/s12985-016-0657-5,PMC5129218,27899161,CC BY,"BACKGROUND: The potential involvement of viruses in inflammatory airway disease (IAD) was previously investigated through either serology or PCR from nasopharyngeal swabs (NS). The aims of this study were to determine the prevalence and incidence of viral genome detection by qPCR in the equine airways, and their association with respiratory clinical signs. METHODS: Both NS and tracheal washes (TW) were collected monthly on 52 Standardbred racehorses at training, over 27 consecutive months (581 samples). Equid herpesviruses (EHV)-1, −4, −2 and −5, equine rhinitis virus-A and -B (ERBV), equine adenovirus-1 and −2, equine coronavirus and equine influenza virus were systematically investigated in both NS and TW. Nasal discharge, coughing, tracheal mucus score and TW neutrophil proportions were simultaneously recorded. RESULTS: Genome for 7/10 viruses were detected at least once throughout the study; up to 4 different viruses being also concomitantly detected. Monthly incidence in TW was respectively 27.9% (EHV-5), 24.8% (EHV-2), 7.1% (ERBV), 3.8% (EHV-4), 1.9% (EAdV1) and 0.2% (EHV-1; ERAV). Neither agreement nor correlation between NS and TW was found for respectively genome detection and viral loads. Detection of viral genome in NS was not associated with any clinical sign. Coughing was significantly associated with TW detection of EHV-2 DNA (OR 3.1; P = 0.01) and ERBV RNA (OR 5.3; P < 0.001). Detection of EHV-2 DNA in TW was also significantly associated with excess tracheal mucus (OR 2.1; P = 0.02). CONCLUSIONS: Detection and quantification of EHV-2 and ERBV by qPCR in TW, but not in NS, should be considered when investigating horses with IAD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0657-5) contains supplementary material, which is available to authorized users.",2016 Nov 29,"['Doubli-Bounoua, Nadia', 'Richard, Eric A.', 'Léon, Albertine', 'Pitel, Pierre-Hugues', 'Pronost, Stéphane', 'Fortier, Guillaume']",Virol J,,,True
9c8a35cb4e5844ead3ef3214b059ba238cd70362,PMC,Bibliometric analysis of publications on Campylobacter: (2000–2015),http://dx.doi.org/10.1186/s41043-016-0076-7,PMC5129233,27899145,CC BY,"BACKGROUND: Campylobacter species are widespread zoonotic pathogens. Campylobacter jejuni causes a form of gastroenteritis called campylobacteriosis. Campylobacter drug resistance is considered a serious threat. In order to better understand national and international research output on Campylobacter, we conducted this bibliometric overview of publications on Campylobacter. This study can be used to assess extent of interaction and response of researchers, food regulators, and health policy makers to global burden of campylobacateriosis. METHODS: Scopus database was used to retrieve publications with the following keywords (Campylobacter/campylobacteriosis, C. jejuni, C. coli). The study period was set from 2000 to 2015. All types of journal documents, excluding errata, were considered. Bibliometric indicators such as annual growth of publications, country contribution, international collaboration, and citation analysis were presented. The quality of retrieved data was indirectly assessed by Hirsch index and impact factor of journals. RESULTS: A total of 5522 documents were retrieved with median (Q1–Q3) citations of 9 (2–23) and h-index of 113. Annual number of publications showed a fluctuating increase. The core leading journals were Applied and Environmental Microbiology journal and Journal of Food Protection with 246 (4.46%) publications for each. The USA (1309; 23.6%) was the most productive country while Danmarks Tekniske Universitet (150; 2.7%) was the most productive institution. Half of the top ten productive countries were European. France had the lowest percentage (33.5%) of articles with international collaboration while Netherlands (57.7%) had the highest percentage of articles with international collaboration. Approximately half (50.1%) of retrieved articles were published in journals under the subject area of “immunology/microbiology”. Main themes in highly cited articles were molecular biology/genetics and public health burden of campylobacteriosis. There were 728 (13.1%) articles on campylobacter-related drug resistance, and the top cited articles focused mainly on increasing resistance to quinolones and fluoroquinolones. CONCLUSIONS: There was a clear increase in number of publications on Campylobacter. Rational use of antimicrobials in humans, poultry, and animals is highly recommended. International collaboration is highly required particularly in implementing new diagnostic screening technologies to minimize global health burden of Campylobacter and ensure food safety.",2016 Nov 29,"['Sweileh, Waleed M.', 'Al-Jabi, Samah W.', 'Sawalha, Ansam F.', 'AbuTaha, Adham S.', 'Zyoud, Sa’ed H.']",J Health Popul Nutr,,,True
aa96296a83b9395223f9a9b1b116f50ae8bcdb11,PMC,Relationship between hospital ward design and healthcare-associated infection rates: a systematic review and meta-analysis,http://dx.doi.org/10.1186/s13756-016-0152-1,PMC5129243,27957323,CC BY,"BACKGROUND: The influence of the hospital’s infrastructure on healthcare-associated colonization and infection rates has thus far infrequently been examined. In this review we examine whether healthcare facility design is a contributing factor to multifaceted infection control strategies. METHODS: We searched PubMed/MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) from 1990 to December 31(st), 2015, with language restriction to English, Spanish, German and French. RESULTS: We identified three studies investigating accessibility of the location of the antiseptic hand rub dispenser. Each of them showed a significant improvement of hand hygiene compliance or agent consumption with the implementation of accessible dispensers near the patient bed. Nine eligible studies evaluated the impact of single-patient rooms on the acquisition of healthcare-associated colonization and infections in comparison to multi-bedrooms or an open ward design. Six of these studies showed a significant benefit of single-patient bedrooms in reducing the healthcare-associated colonization and infection rate, whereas three studies found that single-patient rooms are neither a protective nor risk factor. In meta-analyses, the overall risk ratio for acquisition of healthcare-associated colonization and infection was 0.55 (95% CI: 0.41 to 0.74), for healthcare-associated colonization 0.52 (95% CI: 0.32 to 0.85) and for bacteremia 0.64 (95% CI: 0.53 to 0.76), all in favor of patient care in single-patient bedrooms. CONCLUSION: Implementation of single-patient rooms and easily accessible hand rub dispensers located near the patient’s bed are beneficial for infection control and are useful parts of a multifaceted strategy for reducing healthcare-associated colonization and infections.",2016 Nov 29,"['Stiller, Andrea', 'Salm, Florian', 'Bischoff, Peter', 'Gastmeier, Petra']",Antimicrob Resist Infect Control,,,True
ca5c35779ac657261ff729dd0f8509e1b14a6acd,PMC,Clinical determinants of the severity of Middle East respiratory syndrome (MERS): a systematic review and meta-analysis,http://dx.doi.org/10.1186/s12889-016-3881-4,PMC5129628,27899100,CC BY,"BACKGROUND: While the risk of severe complications of Middle East respiratory syndrome (MERS) and its determinants have been explored in previous studies, a systematic analysis of published articles with different designs and populations has yet to be conducted. The present study aimed to systematically review the risk of death associated with MERS as well as risk factors for associated complications. METHODS: PubMed and Web of Science databases were searched for clinical and epidemiological studies on confirmed cases of MERS. Eligible articles reported clinical outcomes, especially severe complications or death associated with MERS. Risks of admission to intensive care unit (ICU), mechanical ventilation and death were estimated. Subsequently, potential associations between MERS-associated death and age, sex, underlying medical conditions and study design were explored. RESULTS: A total of 25 eligible articles were identified. The case fatality risk ranged from 14.5 to 100%, with the pooled estimate at 39.1%. The risks of ICU admission and mechanical ventilation ranged from 44.4 to 100% and from 25.0 to 100%, with pooled estimates at 78.2 and 73.0%, respectively. These risks showed a substantial heterogeneity among the identified studies, and appeared to be the highest in case studies focusing on ICU cases. We identified older age, male sex and underlying medical conditions, including diabetes mellitus, renal disease, respiratory disease, heart disease and hypertension, as clinical predictors of death associated with MERS. In ICU case studies, the expected odds ratios (OR) of death among patients with underlying heart disease or renal disease to patients without such comorbidities were 0.6 (95% Confidence Interval (CI): 0.1, 4.3) and 0.6 (95% CI: 0.0, 2.1), respectively, while the ORs were 3.8 (95% CI: 3.4, 4.2) and 2.4 (95% CI: 2.0, 2.9), respectively, in studies with other types of designs. CONCLUSIONS: The heterogeneity for the risk of death and severe manifestations was substantially high among the studies, and varying study designs was one of the underlying reasons for this heterogeneity. A statistical estimation of the risk of MERS death and identification of risk factors must be conducted, particularly considering the study design and potential biases associated with case detection and diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-3881-4) contains supplementary material, which is available to authorized users.",2016 Nov 29,"['Matsuyama, Ryota', 'Nishiura, Hiroshi', 'Kutsuna, Satoshi', 'Hayakawa, Kayoko', 'Ohmagari, Norio']",BMC Public Health,,,True
cefbe0e7441f96ec3d0a08e9d7f291dbcf44f4e3,PMC,Interferon α Induces the Apoptosis of Cervical Cancer HeLa Cells by Activating both the Intrinsic Mitochondrial Pathway and Endoplasmic Reticulum Stress-Induced Pathway,http://dx.doi.org/10.3390/ijms17111832,PMC5133833,27827850,CC BY,"The interferon α (IFN-α) has been often used as a sensitizing agent for the treatment of various malignancies such as hepatocellular carcinoma, malignant melanoma, and renal cell cancer by promoting the apoptosis of thesetumor cell types. However, the effect of IFN-α on cervical cancer remains unknown. In this study, HeLa cells were used as a testing model for the treatment of IFN-α on cervical cancer. The results indicate that IFN-α markedly inhibits the proliferation and induces the apoptosis of HeLa cells. The activation of caspase 3, the up-regulation of both Bim and cleaved poly (ADP-ribose) polymerase (PARP) 1, the down-regulation of Bcl-xL, as well as the release of cytochrome c from mitochondria were significantly induced upon IFN-α treatment, indicating that the intrinsic apoptotic pathway could be activated by IFN-α treatment. In addition, caspase 4—which is involved in the endoplasmic reticulum (ER) stress-induced apoptosis—was activated in response to IFN-α treatment. Knocking down caspase 4 by small interfering RNA (siRNA) markedly reduced the IFN-α-mediated cell apoptosis. However, no significant changes in the expressions of caspases 8 and 10 were observed upon IFN-α treatment, indicating that the apoptosis caused by IFN-α might be independent of the extrinsic apoptotic pathway. These findings suggest that IFN-α may possess anti-cervical cancer capacity by activating cell apoptosis via the intrinsic mitochondrial pathway and caspase-4-related ER stress-induced pathway.",2016 Nov 2,"['Shi, Wei-Ye', 'Cao, Cheng', 'Liu, Li']",Int J Mol Sci,,,True
9b5f7347b52c46ad29b1991560e6251bfdfd8df2,PMC,A Melting Curve-Based Multiplex RT-qPCR Assay for Simultaneous Detection of Four Human Coronaviruses,http://dx.doi.org/10.3390/ijms17111880,PMC5133880,27886052,CC BY,"Human coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1 are common respiratory viruses associated with acute respiratory infection. They have a global distribution. Rapid and accurate diagnosis of HCoV infection is important for the management and treatment of hospitalized patients with HCoV infection. Here, we developed a melting curve-based multiplex RT-qPCR assay for simultaneous detection of the four HCoVs. In the assay, SYTO 9 was used to replace SYBR Green I as the fluorescent dye, and GC-modified primers were designed to improve the melting temperature (Tm) of the specific amplicon. The four HCoVs were clearly distinguished by characteristic melting peaks in melting curve analysis. The detection sensitivity of the assay was 3 × 10(2) copies for HCoV-OC43, and 3 × 10(1) copies for HCoV-NL63, HCoV-229E and HCoV-HKU1 per 30 μL reaction. Clinical evaluation and sequencing confirmation demonstrated that the assay was specific and reliable. The assay represents a sensitive and reliable method for diagnosis of HCoV infection in clinical samples.",2016 Nov 23,"['Wan, Zhenzhou', 'Zhang, Ya’nan', 'He, Zhixiang', 'Liu, Jia', 'Lan, Ke', 'Hu, Yihong', 'Zhang, Chiyu']",Int J Mol Sci,,,True
25e089b28ebc09fee5ea9ce51d0c12043fa3834c,PMC,A Melting Curve-Based Multiplex RT-qPCR Assay for Simultaneous Detection of Four Human Coronaviruses,http://dx.doi.org/10.3390/ijms17111880,PMC5133880,27886052,CC BY,"Human coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1 are common respiratory viruses associated with acute respiratory infection. They have a global distribution. Rapid and accurate diagnosis of HCoV infection is important for the management and treatment of hospitalized patients with HCoV infection. Here, we developed a melting curve-based multiplex RT-qPCR assay for simultaneous detection of the four HCoVs. In the assay, SYTO 9 was used to replace SYBR Green I as the fluorescent dye, and GC-modified primers were designed to improve the melting temperature (Tm) of the specific amplicon. The four HCoVs were clearly distinguished by characteristic melting peaks in melting curve analysis. The detection sensitivity of the assay was 3 × 10(2) copies for HCoV-OC43, and 3 × 10(1) copies for HCoV-NL63, HCoV-229E and HCoV-HKU1 per 30 μL reaction. Clinical evaluation and sequencing confirmation demonstrated that the assay was specific and reliable. The assay represents a sensitive and reliable method for diagnosis of HCoV infection in clinical samples.",2016 Nov 23,"['Wan, Zhenzhou', 'Zhang, Ya’nan', 'He, Zhixiang', 'Liu, Jia', 'Lan, Ke', 'Hu, Yihong', 'Zhang, Chiyu']",Int J Mol Sci,,,False
4e687843401f339f6b5e8ae35626d0d0ef0b3e7e,PMC,Financing strategies to improve essential public health equalization and its effects in China,http://dx.doi.org/10.1186/s12939-016-0482-x,PMC5134004,27905941,CC BY,"BACKGROUND: In 2009, China launched a health reform to promote the equalization of national essential public health services package (NEPHSP). The present study aimed to describe the financing strategies and mechanisms to improve access to public health for all, identify the strengths and weaknesses of the different approaches, and showed evidence on equity improvement among different regions. METHODS: We reviewed the relevant literatures and identified 208 articles after screening and quality assessment and conducted six key informants’ interviews. Secondary data on national and local government health expenditures, NEPHSP coverage and health indicators in 2003–2014 were collected, descriptive and equity analyses were used. RESULTS: Before 2009, the government subsidy to primary care institutions (PCIs) were mainly used for basic construction and a small part of personnel expenses. Since 2009, the new funds for NEPHSP have significantly expanded service coverage and population coverage. These funds have been allocated by central, provincial, municipal and county governments at different proportions in China’s tax distribution system. Due to the fiscal transfer payment, the Central Government allocated more subsides to less-developed western regions and all the funds were managed in a specific account. Several types of payment methods have been adopted including capitation, pay for performance (P4P), pay for service items, global budget and public health voucher, to address issues from both the supply and demand sides. The equalization of NEPHSP did well through the establishment of health records, systematic care of children and maternal women, etc. Our data showed that the gap between the eastern, central and western regions narrowed. However the coverage for migrants was still low and performance was needed improving in effectiveness of managing patients with chronic diseases. CONCLUSIONS: The delivery of essential public health services was highly influenced by public fiscal policy, and the implementation of health reform since 2009 has led the public health development towards the right direction. However China still needs to increase the fiscal investments to expand service coverage as well as promote the quality of public health services and equality among regions. Independent scientific monitoring and evaluation are also needed.",2016 Dec 1,"['Yang, Li', 'Sun, Li', 'Wen, Liankui', 'Zhang, Huyang', 'Li, Chenyang', 'Hanson, Kara', 'Fang, Hai']",Int J Equity Health,,,True
8c6ca63f974a55bcab6f773fc9cda85c938b93eb,PMC,Sickle-cell disease in febrile children living in a rural village of Madagascar and association with malaria and respiratory infections,http://dx.doi.org/10.1186/s12878-016-0069-1,PMC5134128,27980789,CC BY,"BACKGROUND: In Madagascar, the last study on sickle cell disease (SCD) was done in the early 1980s. The country is known as endemic for malaria and respiratory infections. The main objective of this study was to estimate the prevalence of SCD; the secondary objective was to evaluate its association with malaria and respiratory infections. METHODS: This is a cross-sectional study which was carried out in a rural village in the south east coast of Madagascar between May 2011 and November 2013. Participants were children aged between 2–59 months presenting with fever measured by axillary temperature ≥37.5 °C at inclusion. Genotyping of haemoglobin S was done by PCR and malaria was diagnosed by Rapid Diagnostic Test. Research for viral and atypical bacterial respiratory pathogens was performed on nasopharyngeal swabs. Uni-and multivariate polytomous logistic regression was done to assess associations between microbiological results and SCD status, with HbAA phenotype as reference. RESULTS: A total of 807 children were analysed. Prevalence of SCD among febrile children was 2.4% (95% CI, 1.5–3.7%) and that of SCT was 23.8% (95% CI, 20.9–26.9%). There was no difference in the prevalence of malaria infection according to haemoglobin status (p = 0.3). Rhinovirus (22.5%), adenovirus (14.1%), and bocavirus (11.6%) were the most common respiratory pathogens detected. After univariate analysis, patients with SCD were more frequently infected by parechovirus (p = 0.01), while patients with SCT were more prone to RSV A or B infection (p = 0.01). After multivariate analysis, HbAS phenotype was associated with higher risk of RSV A and B infection compared to HbAA (adjusted OR = 1.9; 95% CI: 1.2–3.1, p = 0.009), while HbSS phenotype was associated with higher risk of parechovirus infection (adjusted OR = 6.0; 95% CI: 1.1–31.3, p = 0.03) compared to HbAA, independently of age, gender, period per quarter, and the other viruses. CONCLUSION: The prevalence of SCD among under-five children presenting with fever was high in the study population. No association was found between SCT and malaria but few viruses, especially parechovirus, seem to play an important role in the occurrence of pneumoniae among SCD patients.",2016 Dec 1,"['Maeder, Muriel N.', 'Rabezanahary, Henintsoa M.', 'Zafindraibe, Norosoa J.', 'Randriatiana, Martin Raoelina', 'Rasamoelina, Tahinamandranto', 'Rakotoarivo, Andry T.', 'Vanhems, Philippe', 'Hoffmann, Jonathan', 'Bénet, Thomas', 'Rakoto Andrianarivelo, Mala', 'Rakoto-Alson, Olivat A.']",BMC Hematol,,,True
41f31582cb50c99b10a376f465107d82bacf135c,PMC,The impact of epidemics on labor market: identifying victims of the Middle East Respiratory Syndrome in the Korean labor market,http://dx.doi.org/10.1186/s12939-016-0483-9,PMC5134239,27905938,CC BY,"BACKGROUND: The vulnerability approach suggests that disasters such as epidemics have different effects according not only to physical vulnerability but also to economic class (status). This paper examines the effect of the Middle East Respiratory Syndrome epidemic on the labor market to investigate whether vulnerable groups become more vulnerable due to an interaction between the socio-economic structure and physical risk. METHODS: This paper examines the effect of the Middle East Respiratory Syndrome epidemic on the labor market by considering unemployment status, job status, working hours, reason for unemployment and underemployment status. In particular, the study investigates whether the U-shaped curve becomes a J-shaped curve due to the interaction between medical vulnerability and labor market vulnerability after an outbreak, assuming that the relative vulnerability in the labor market by age shows a U curve with peaks for the young group and middle aged and old aged groups using the Economically Active Population Survey. We use the difference in difference approach and also conduct a falsification check and robustness check. RESULTS: The results suggest that older workers faced a higher possibility of unemployment after the Middle East Respiratory Syndrome outbreak. In particular, they experienced higher involuntary unemployment and underemployment status as well as decreased working hours. It was confirmed that the relative vulnerability of the labor market for older workers was higher than for the other age groups after the epidemic outbreak due to the double whammy of vulnerability in the medical and labor market. The vulnerability in the young group partially increased compared to the 30s and 40s age groups due to their relative vulnerability in the labor market despite being healthy. We find that assuming the relative vulnerability in the existing labor market shows a U shape with age increase, the U-shaped curve became J-shaped after the outbreak. CONCLUSIONS: Disasters like epidemics can occur unexpectedly and affect certain groups more than other. Therefore, medical protection should be enhanced for groups vulnerable to disease and economic measures are also required for the protection of their livelihoods in the labor market to prevent unemployment stemming from inequality.",2016 Dec 1,"['Lee, Ayoung', 'Cho, Joonmo']",Int J Equity Health,,,True
7f6d6d5cf7a484c164c955ff15a32758e1ab3943,PMC,An Investigation of the Outcomes of PGY Students’ Cognition of and Persistent Behavior in Learning through the Intervention of the Flipped Classroom in Taiwan,http://dx.doi.org/10.1371/journal.pone.0167598,PMC5135136,27911937,CC BY,"The Postgraduate Year (PGY) Program allows doctors-in-training to learn about the diagnosis, treatment and nursing of various common, general diseases. These items form the core curriculum and are mostly learned through caring for patients and clinical teaching. Doctors-in-training are evaluated for their knowledge through written tests or assignments, based on which the effectiveness of their training is also assessed; however, this generally produces a negative learning attitude among them. So we introduced the flipped classroom into PGY training program to change PGY students’ learning behavior. Although the flipped classroom is highly valued and has been practiced by teachers in schools of various levels, very few attempts have been made until now to report the learning outcomes achieved through the flipped classroom by means of rigorous research methods. Therefore we tried to employed Ajzen and Fishbein’s (1980) theory of reasoned action and Bandura’s self-efficacy to predict and explain the participants’ behavioral intention when participating in the core curriculum learning of the flipped classroom and to assess the change in students’ learning behavior and learning effectiveness. From August 2013 to July 2014, 39 PGY students from the General Surgery of the Tri-Service General Hospital were selected as the participants of this study. The control group included 43 students of the previous year, that is, the year before the intervention of the flipped classroom. A comparative analysis was performed. The questionnaire’s related matrices indicated highest correlation between self-efficacy and behavioral intention (r = 0.491, P < 0.01), followed by attitude (r = 0.365, P < 0.01) and subjective norms (r = 0.360, P < 0.01.) All three showed positive correlations with behavioral intention; among attitude, subjective norms, and self-efficacy, the pairwise correlations also reached significance level. The flipped classroom can indeed change PGY students’ the learning behavior from “passive learning” to “active learning.”",2016 Dec 2,"['Hsu, Sheng-Der', 'Chen, Cheng-Jueng', 'Chang, Wei-Kuo', 'Hu, Yih-Jin']",PLoS One,,,True
6cc00d24747f80a0e94f4dbdebcd9cc84b7e086f,PMC,An observational study of febrile seizures: the importance of viral infection and immunization,http://dx.doi.org/10.1186/s12887-016-0740-5,PMC5135752,27914475,CC BY,"BACKGROUND: Febrile seizures are common in young children. Annual peaks in incidence mirror increased respiratory virus activity during winter. Limited virological data are available using modern diagnostic techniques for children with febrile seizures. We aimed to determine the frequency of detection of specific viral pathogens in children with febrile seizures, to describe risk factors including recent vaccination and clinical features associated with specific etiologies. METHODS: An observational study was performed. Children aged 6 months to 5 years presenting to the Emergency Department of a tertiary children’s hospital in Western Australia with febrile seizures were enrolled between March 2012 and October 2013. Demographic, clinical data and vaccination history were collected, and virological testing was performed on per-nasal and per-rectal samples. RESULTS: One hundred fifty one patients (72 female; median age 1.7y; range 6 m-4y9m) were enrolled. Virological testing was completed for 143/151 (95%). At least one virus was detected in 102/143 patients (71%). The most commonly identified were rhinoviruses (31/143, 22%), adenovirus (30/151, 21%), enteroviruses, (28/143, 20%), influenza (19/143, 13%) and HHV6 (17/143, 12%). More than one virus was found in 48/143 (34%). No significant clinical differences were observed when children with a pathogen identified were compared with those with no pathogen detected. Febrile seizures occurred within 14 days of vaccine administration in 16/151 (11%). CONCLUSION: At least one virus was detected in over two thirds of cases tested (commonly picornaviruses, adenovirus and influenza). Viral co-infections were frequently identified. Febrile seizures occurred infrequently following immunization.",2016 Dec 3,"['Francis, Joshua R.', 'Richmond, Peter', 'Robins, Christine', 'Lindsay, Katie', 'Levy, Avram', 'Effler, Paul V.', 'Borland, Meredith', 'Blyth, Christopher C.']",BMC Pediatr,,,True
48c1c1a52958c6fd6f18ff10121c1336b9eb1395,PMC,China’s health assistance to Africa: opportunism or altruism?,http://dx.doi.org/10.1186/s12992-016-0217-1,PMC5135833,27912773,CC BY,"China has made substantial health commitments to Africa in the past several decades. However, while much has been written regarding China-Africa aid overall, relatively little attention has been given to China’s health aid. To better understand these investments, we provide an overview of the current framework and characteristics of China’s health aid to Africa. China’s health assistance has been perceived by some as opportunistic, largely as a demonstration of China’s engagement in “soft power” and an attempt to enhance its access to natural resources and political favors by African countries. Others have attributed altruistic intent, aiming to support the advancement of the health of populations in the African continent with a “no strings attached” approach. Our overview demonstrated that despite the magnitude of China’s health assistance, many questions remain regarding the scope of this aid, its effectiveness and the governance mechanisms that guide the conceptualization and implementation of such efforts. We also identified the need for a systematic and rigorous evaluation of the various elements of China’s health assistance to African countries in order to gain a deeper understanding of how priorities and allocations for health aid are determined, how such aid fits within the specific African country’s health strategies and to assess the effectiveness of such aid. Insights garnered through such an assessment could help determine future priorities for investment as well as inform efforts to optimize the value of China's aid for the populations of the recipient countries.",2016 Dec 3,"['Lin, Shuang', 'Gao, Liangmin', 'Reyes, Melissa', 'Cheng, Feng', 'Kaufman, Joan', 'El-Sadr, Wafaa M.']",Global Health,,,True
e28eedb8b780c3b08fa6a3d7d4c617f9587adc9a,PMC,Viral vector-based influenza vaccines,http://dx.doi.org/10.1080/21645515.2016.1210729,PMC5137548,27455345,CC BY,"Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors.",2016 Jul 25,"['de Vries, Rory D.', 'Rimmelzwaan, Guus F.']",Hum Vaccin Immunother,,,True
ef3d6cabc804e5eb587b34249b539c1b5efa4cc4,PMC,Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study,http://dx.doi.org/10.1038/srep38532,PMC5138590,27922126,CC BY,"Mixed viral and bacterial infections are widely described in community-acquired pneumonia; however, the clinical implications of co-infection on the associated immunopathology remain poorly studied. In this study, microRNA, mRNA and cytokine/chemokine secretion profiling were investigated for human monocyte-derived macrophages infected in-vitro with Influenza virus A/H1N1 and/or Streptococcus pneumoniae. We observed that the in-vitro co-infection synergistically increased interferon-γ-induced protein-10 (CXCL10, IP-10) expression compared to the singly-infected cells conditions. We demonstrated that endogenous miRNA-200a-3p, whose expression was synergistically induced following co-infection, indirectly regulates CXCL10 expression by targeting suppressor of cytokine signaling-6 (SOCS-6), a well-known regulator of the JAK-STAT signaling pathway. Additionally, in a subsequent clinical pilot study, immunomodulators levels were evaluated in samples from 74 children (≤5 years-old) hospitalized with viral and/or bacterial community-acquired pneumonia. Clinically, among the 74 cases of pneumonia, patients with identified mixed-detection had significantly higher (3.6-fold) serum IP-10 levels than those with a single detection (P = 0.03), and were significantly associated with severe pneumonia (P < 0.01). This study demonstrates that viral and bacterial co-infection modulates the JAK-STAT signaling pathway and leads to exacerbated IP-10 expression, which could play a major role in the pathogenesis of pneumonia.",2016 Dec 6,"['Hoffmann, Jonathan', 'Machado, Daniela', 'Terrier, Olivier', 'Pouzol, Stephane', 'Messaoudi, Mélina', 'Basualdo, Wilma', 'Espínola, Emilio E', 'Guillen, Rosa M.', 'Rosa-Calatrava, Manuel', 'Picot, Valentina', 'Bénet, Thomas', 'Endtz, Hubert', 'Russomando, Graciela', 'Paranhos-Baccalà, Gláucia']",Sci Rep,,,True
f18711ed6bde09aa40add3f7995993450056ec1d,PMC,Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study,http://dx.doi.org/10.1038/srep38532,PMC5138590,27922126,CC BY,"Mixed viral and bacterial infections are widely described in community-acquired pneumonia; however, the clinical implications of co-infection on the associated immunopathology remain poorly studied. In this study, microRNA, mRNA and cytokine/chemokine secretion profiling were investigated for human monocyte-derived macrophages infected in-vitro with Influenza virus A/H1N1 and/or Streptococcus pneumoniae. We observed that the in-vitro co-infection synergistically increased interferon-γ-induced protein-10 (CXCL10, IP-10) expression compared to the singly-infected cells conditions. We demonstrated that endogenous miRNA-200a-3p, whose expression was synergistically induced following co-infection, indirectly regulates CXCL10 expression by targeting suppressor of cytokine signaling-6 (SOCS-6), a well-known regulator of the JAK-STAT signaling pathway. Additionally, in a subsequent clinical pilot study, immunomodulators levels were evaluated in samples from 74 children (≤5 years-old) hospitalized with viral and/or bacterial community-acquired pneumonia. Clinically, among the 74 cases of pneumonia, patients with identified mixed-detection had significantly higher (3.6-fold) serum IP-10 levels than those with a single detection (P = 0.03), and were significantly associated with severe pneumonia (P < 0.01). This study demonstrates that viral and bacterial co-infection modulates the JAK-STAT signaling pathway and leads to exacerbated IP-10 expression, which could play a major role in the pathogenesis of pneumonia.",2016 Dec 6,"['Hoffmann, Jonathan', 'Machado, Daniela', 'Terrier, Olivier', 'Pouzol, Stephane', 'Messaoudi, Mélina', 'Basualdo, Wilma', 'Espínola, Emilio E', 'Guillen, Rosa M.', 'Rosa-Calatrava, Manuel', 'Picot, Valentina', 'Bénet, Thomas', 'Endtz, Hubert', 'Russomando, Graciela', 'Paranhos-Baccalà, Gláucia']",Sci Rep,,,False
6ebbce608cb316b579ed926190d068a6fa90534a,PMC,‘The Microbiome and the Pathophysiology of Asthma’,http://dx.doi.org/10.1186/s12931-016-0479-4,PMC5139145,27919249,CC BY,"Asthma is a chronic respiratory disease whose prevalence is increasing in the western world. Recently research has begun to focus on the role the microbiome plays in asthma pathogenesis in the hope of further understanding this respiratory disorder. Considered sterile until recently, the lungs have revealed themselves to contain a unique microbiota. A shift towards molecular methods for the quantification and sequencing of microbial DNA has revealed that the airways harbour a unique microbiota with apparent, reproducible differences present between healthy and diseased lungs. There is a hope that in classifying the microbial load of the asthmatic airway an insight may be afforded as to the possible role pulmonary microbes may have in propagating an asthmatic airway response. This could potentially pave the way for new therapeutic strategies for the treatment of chronic lung conditions such as asthma.",2016 Dec 5,"['Sullivan, Ashley', 'Hunt, Eoin', 'MacSharry, John', 'Murphy, Desmond M.']",Respir Res,,,True
d3cbb775040a7d1eac36c6615653b2d94f6c6c13,PMC,Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections,http://dx.doi.org/10.1038/emi.2016.69,PMC5141262,27436362,CC BY,"Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.",2016 Jul 20,"['Horm, Srey Viseth', 'Tarantola, Arnaud', 'Rith, Sareth', 'Ly, Sowath', 'Gambaretti, Juliette', 'Duong, Veasna', 'Y, Phalla', 'Sorn, San', 'Holl, Davun', 'Allal, Lotfi', 'Kalpravidh, Wantanee', 'Dussart, Philippe', 'Horwood, Paul F', 'Buchy, Philippe']",Emerg Microbes Infect,,,True
4ebf0b2d466494a1445783fc4c415a0ef8ecbd36,PMC,Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections,http://dx.doi.org/10.1038/emi.2016.69,PMC5141262,27436362,CC BY,"Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.",2016 Jul 20,"['Horm, Srey Viseth', 'Tarantola, Arnaud', 'Rith, Sareth', 'Ly, Sowath', 'Gambaretti, Juliette', 'Duong, Veasna', 'Y, Phalla', 'Sorn, San', 'Holl, Davun', 'Allal, Lotfi', 'Kalpravidh, Wantanee', 'Dussart, Philippe', 'Horwood, Paul F', 'Buchy, Philippe']",Emerg Microbes Infect,,,False
46934907d830de62eb5b4331a75b3332a9c0088c,PMC,Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections,http://dx.doi.org/10.1038/emi.2016.69,PMC5141262,27436362,CC BY,"Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.",2016 Jul 20,"['Horm, Srey Viseth', 'Tarantola, Arnaud', 'Rith, Sareth', 'Ly, Sowath', 'Gambaretti, Juliette', 'Duong, Veasna', 'Y, Phalla', 'Sorn, San', 'Holl, Davun', 'Allal, Lotfi', 'Kalpravidh, Wantanee', 'Dussart, Philippe', 'Horwood, Paul F', 'Buchy, Philippe']",Emerg Microbes Infect,,,False
49fd6f93367918d60b747f28a90e2ae4a85ff52a,PMC,Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections,http://dx.doi.org/10.1038/emi.2016.69,PMC5141262,27436362,CC BY,"Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.",2016 Jul 20,"['Horm, Srey Viseth', 'Tarantola, Arnaud', 'Rith, Sareth', 'Ly, Sowath', 'Gambaretti, Juliette', 'Duong, Veasna', 'Y, Phalla', 'Sorn, San', 'Holl, Davun', 'Allal, Lotfi', 'Kalpravidh, Wantanee', 'Dussart, Philippe', 'Horwood, Paul F', 'Buchy, Philippe']",Emerg Microbes Infect,,,False
e2c481329825d40d30efd7656bfbd28a3105707b,PMC,Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections,http://dx.doi.org/10.1038/emi.2016.69,PMC5141262,27436362,CC BY,"Surveillance for avian influenza viruses (AIVs) in poultry and environmental samples was conducted in four live-bird markets in Cambodia from January through November 2013. Through real-time RT-PCR testing, AIVs were detected in 45% of 1048 samples collected throughout the year. Detection rates ranged from 32% and 18% in duck and chicken swabs, respectively, to 75% in carcass wash water samples. Influenza A/H5N1 virus was detected in 79% of samples positive for influenza A virus and 35% of all samples collected. Sequence analysis of full-length haemagglutinin (HA) and neuraminidase (NA) genes from A/H5N1 viruses, and full-genome analysis of six representative isolates, revealed that the clade 1.1.2 reassortant virus associated with Cambodian human cases during 2013 was the only A/H5N1 virus detected during the year. However, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of HA and NA genes revealed co-circulation of at least nine low pathogenic AIVs from HA1, HA2, HA3, HA4, HA6, HA7, HA9, HA10 and HA11 subtypes. Four repeated serological surveys were conducted throughout the year in a cohort of 125 poultry workers. Serological testing found an overall prevalence of 4.5% and 1.8% for antibodies to A/H5N1 and A/H9N2, respectively. Seroconversion rates of 3.7 and 0.9 cases per 1000 person-months participation were detected for A/H5N1 and A/H9N2, respectively. Peak AIV circulation was associated with the Lunar New Year festival. Knowledge of periods of increased circulation of avian influenza in markets should inform intervention measures such as market cleaning and closures to reduce risk of human infections and emergence of novel AIVs.",2016 Jul 20,"['Horm, Srey Viseth', 'Tarantola, Arnaud', 'Rith, Sareth', 'Ly, Sowath', 'Gambaretti, Juliette', 'Duong, Veasna', 'Y, Phalla', 'Sorn, San', 'Holl, Davun', 'Allal, Lotfi', 'Kalpravidh, Wantanee', 'Dussart, Philippe', 'Horwood, Paul F', 'Buchy, Philippe']",Emerg Microbes Infect,,,False
9cfada440e426dd4dabdb499d47ab2e7f9bad08c,PMC,Antiviral Innate Immune Response Interferes with the Formation of Replication-Associated Membrane Structures Induced by a Positive-Strand RNA Virus,http://dx.doi.org/10.1128/mBio.01991-16,PMC5142621,27923923,CC BY,"Infection with nidoviruses like corona- and arteriviruses induces a reticulovesicular network of interconnected endoplasmic reticulum (ER)-derived double-membrane vesicles (DMVs) and other membrane structures. This network is thought to accommodate the viral replication machinery and protect it from innate immune detection. We hypothesized that the innate immune response has tools to counteract the formation of these virus-induced replication organelles in order to inhibit virus replication. Here we have investigated the effect of type I interferon (IFN) treatment on the formation of arterivirus-induced membrane structures. Our approach involved ectopic expression of arterivirus nonstructural proteins nsp2 and nsp3, which induce DMV formation in the absence of other viral triggers of the interferon response, such as replicating viral RNA. Thus, this setup can be used to identify immune effectors that specifically target the (formation of) virus-induced membrane structures. Using large-scale electron microscopy mosaic maps, we found that IFN-β treatment significantly reduced the formation of the membrane structures. Strikingly, we also observed abundant stretches of double-membrane sheets (a proposed intermediate of DMV formation) in IFN-β-treated samples, suggesting the disruption of DMV biogenesis. Three interferon-stimulated gene products, two of which have been reported to target the hepatitis C virus replication structures, were tested for their possible involvement, but none of them affected membrane structure formation. Our study reveals the existence of a previously unknown innate immune mechanism that antagonizes the viral hijacking of host membranes. It also provides a solid basis for further research into the poorly understood interactions between the innate immune system and virus-induced replication structures.",2016 Dec 6,"['Oudshoorn, Diede', 'van der Hoeven, Barbara', 'Limpens, Ronald W. A. L.', 'Beugeling, Corrine', 'Snijder, Eric J.', 'Bárcena, Montserrat', 'Kikkert, Marjolein']",mBio,,,True
62af9e71368a90bd8fce0347e90527e3e4da3800,PMC,Type 1 Interferons and NK Cells Limit Murine Cytomegalovirus Escape from the Lymph Node Subcapsular Sinus,http://dx.doi.org/10.1371/journal.ppat.1006069,PMC5142805,27926941,CC0,"Cytomegaloviruses (CMVs) establish chronic, systemic infections. Peripheral infection spreads via lymph nodes, which are also a focus of host defence. Thus, this is a point at which systemic infection spread might be restricted. Subcapsular sinus macrophages (SSM) captured murine CMV (MCMV) from the afferent lymph and poorly supported its replication. Blocking the type I interferon (IFN-I) receptor (IFNAR) increased MCMV infection of SSM and of the fibroblastic reticular cells (FRC) lining the subcapsular sinus, and accelerated viral spread to the spleen. Little splenic virus derived from SSM, arguing that they mainly induce an anti-viral state in the otherwise susceptible FRC. NK cells also limited infection, killing infected FRC and causing tissue damage. They acted independently of IFN-I, as IFNAR blockade increased NK cell recruitment, and NK cell depletion increased infection in IFNAR-blocked mice. Thus SSM restricted MCMV infection primarily though IFN-I, with NK cells providing a second line of defence. The capacity of innate immunity to restrict MCMV escape from the subcapsular sinus suggested that enhancing its recruitment might improve infection control.",2016 Dec 7,"['Farrell, Helen E.', 'Bruce, Kimberley', 'Lawler, Clara', 'Cardin, Rhonda D.', 'Davis-Poynter, Nicholas J.', 'Stevenson, Philip G.']",PLoS Pathog,,,True
790261c395cc8a2413ec034f450e67e36f5e8b0f,PMC,Camels and Climate Resilience: Adaptation in Northern Kenya,http://dx.doi.org/10.1007/s10745-016-9858-1,PMC5143358,28018023,CC BY,"In the drylands of Africa, pastoralists have been facing new challenges, including those related to environmental shocks and stresses. In northern Kenya, under conditions of reduced rainfall and more frequent droughts, one response has been for pastoralists to focus increasingly on camel herding. Camels have started to be kept at higher altitudes and by people who rarely kept camels before. The development has been understood as a climate change adaptation strategy and as a means to improve climate resilience. Since 2003, development organizations have started to further the trend by distributing camels in the region. Up to now, little has been known about the nature of, reasons for, or ramifications of the increased reliance on camels. The paper addresses these questions and concludes that camels improve resilience in this dryland region, but only under certain climate change scenarios, and only for some groups.",2016 Nov 12,"['Watson, Elizabeth E.', 'Kochore, Hassan H.', 'Dabasso, Bulle Hallo']",Hum Ecol Interdiscip J,,,True
df61f934c991b4b4b08e1ec28804812ec0629ea1,PMC,TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK–STAT signaling pathway,http://dx.doi.org/10.1038/cddis.2016.146,PMC5143376,27253403,CC BY,"We have previously observed the downregulation of TMEM2 in the liver tissue of patients with chronic hepatitis B virus (HBV) infection and in HepG2.2.15 cells with HBV genomic DNA. In the present study, we investigated the role and mechanism of TMEM2 in HepG2 and HepG2.2.15 during HBV infection HepG2 and HepG2.2.15. HepG2 shTMEM2 cells with stable TMEM2 knockdown and HepG2 TMEM2 and HepG2.2.15 TMEM2 cells with stable TMEM2 overexpression were established using lentivirus vectors. We observed reduced expression of TMEM2 in HBV-infected liver tissues and HepG2.2.15 cells. HBsAg, HBcAg, HBV DNA, and HBV cccDNA levels were significantly increased in HepG2 shTMEM2 cells but decreased in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells compared with naive HepG2 cells. On the basis of the western blotting results, the JAK–STAT signaling pathway was inhibited in HepG2 shTMEM2 cells but activated in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells. In addition, reduced and increased expression of the antiviral proteins MxA and OAS1 was observed in TMEM2-silenced cells (HepG2 shTMEM2 cells) and TMEM2-overexpressing cells (HepG2 TMEM2 and HepG2.2.15 TMEM2 cells), respectively. The expression of Interferon regulatory factor 9 (IRF9) was not affected by TMEM2. However, we found that overexpression and knockdown of TMEM2, respectively, promoted and inhibited importation of IRF9 into nuclei. The luciferase reporter assay showed that IRF9 nuclear translocation affected interferon-stimulated response element activities. In addition, the inhibitory effects of TMEM2 on HBV infection in HepG2 shTMEM2 cells was significantly enhanced by pre-treatment with interferon but significantly inhibited in HepG2.2.15 TMEM2 cells by pre-treatment with JAK1 inhibitor. TMEM2 inhibits HBV infection in HepG2 and HepG2.2.15 by activating the JAK–STAT signaling pathway.",2016 Jun 2,"['Zhu, X', 'Xie, C', 'Li, Y-m', 'Huang, Z-l', 'Zhao, Q-y', 'Hu, Z-x', 'Wang, P-p', 'Gu, Y-r', 'Gao, Z-l', 'Peng, L']",Cell Death Dis,,,True
3a5bfccbd47694771018f0ee03b0eeedfeeb2ef9,PMC,Spatiotemporal Analysis of the 2014 Ebola Epidemic in West Africa,http://dx.doi.org/10.1371/journal.pcbi.1005210,PMC5145133,27930675,CC BY,"In 2014–2016, Guinea, Sierra Leone and Liberia in West Africa experienced the largest and longest Ebola epidemic since the discovery of the virus in 1976. During the epidemic, incidence data were collected and published at increasing resolution. To monitor the epidemic as it spread within and between districts, we develop an analysis method that exploits the full spatiotemporal resolution of the data by combining a local model for time-varying effective reproduction numbers with a gravity-type model for spatial dispersion of the infection. We test this method in simulations and apply it to the weekly incidences of confirmed and probable cases per district up to June 2015, as reported by the World Health Organization. Our results indicate that, of the newly infected cases, only a small percentage, between 4% and 10%, migrates to another district, and a minority of these migrants, between 0% and 23%, leave their country. The epidemics in the three countries are found to be similar in estimated effective reproduction numbers, and in the probability of importing infection into a district. The countries might have played different roles in cross-border transmissions, although a sensitivity analysis suggests that this could also be related to underreporting. The spatiotemporal analysis method can exploit available longitudinal incidence data at different geographical locations to monitor local epidemics, determine the extent of spatial spread, reveal the contribution of local and imported cases, and identify sources of introductions in uninfected areas. With good quality data on incidence, this data-driven method can help to effectively control emerging infections.",2016 Dec 8,"['Backer, Jantien A.', 'Wallinga, Jacco']",PLoS Comput Biol,,,True
126fe65d101309b6cfa1b133e0036082572b49d8,PMC,Spatiotemporal Analysis of the 2014 Ebola Epidemic in West Africa,http://dx.doi.org/10.1371/journal.pcbi.1005210,PMC5145133,27930675,CC BY,"In 2014–2016, Guinea, Sierra Leone and Liberia in West Africa experienced the largest and longest Ebola epidemic since the discovery of the virus in 1976. During the epidemic, incidence data were collected and published at increasing resolution. To monitor the epidemic as it spread within and between districts, we develop an analysis method that exploits the full spatiotemporal resolution of the data by combining a local model for time-varying effective reproduction numbers with a gravity-type model for spatial dispersion of the infection. We test this method in simulations and apply it to the weekly incidences of confirmed and probable cases per district up to June 2015, as reported by the World Health Organization. Our results indicate that, of the newly infected cases, only a small percentage, between 4% and 10%, migrates to another district, and a minority of these migrants, between 0% and 23%, leave their country. The epidemics in the three countries are found to be similar in estimated effective reproduction numbers, and in the probability of importing infection into a district. The countries might have played different roles in cross-border transmissions, although a sensitivity analysis suggests that this could also be related to underreporting. The spatiotemporal analysis method can exploit available longitudinal incidence data at different geographical locations to monitor local epidemics, determine the extent of spatial spread, reveal the contribution of local and imported cases, and identify sources of introductions in uninfected areas. With good quality data on incidence, this data-driven method can help to effectively control emerging infections.",2016 Dec 8,"['Backer, Jantien A.', 'Wallinga, Jacco']",PLoS Comput Biol,,,False
d955f71fe354a87e671999a6a0a17b88376bcf8c,PMC,Allelic Variation in CXCL16 Determines CD3(+) T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion,http://dx.doi.org/10.1371/journal.pgen.1006467,PMC5145142,27930647,CC BY,"Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10–70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s) of CD3(+) T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3(+) T lymphocyte susceptible phenotype are at less risk of becoming long-term virus carriers. A genome wide association study (GWAS) using the Illumina Equine SNP50 chip revealed that the ability of EAV to infect CD3(+) T lymphocytes and establish long-term carrier status in stallions correlated with a region within equine chromosome 11. Here we identified the gene and mutations responsible for these phenotypes. Specifically, the work implicated three allelic variants of the equine orthologue of CXCL16 (EqCXCL16) that differ by four non-synonymous nucleotide substitutions (XM_00154756; c.715 A → T, c.801 G → C, c.804 T → A/G, c.810 G → A) within exon 1. This resulted in four amino acid changes with EqCXCL16S (XP_001504806.1) having Phe, His, Ile and Lys as compared to EqCXL16R having Tyr, Asp, Phe, and Glu at 40, 49, 50, and 52, respectively. Two alleles (EqCXCL16Sa, EqCXCL16Sb) encoded identical protein products that correlated strongly with long-term EAV persistence in stallions (P<0.000001) and are required for in vitro CD3(+) T lymphocyte susceptibility to EAV infection. The third (EqCXCL16R) was associated with in vitro CD3(+) T lymphocyte resistance to EAV infection and a significantly lower probability for establishment of the long-term carrier state (viral persistence) in the male reproductive tract. EqCXCL16Sa and EqCXCL16Sb exert a dominant mode of inheritance. Most importantly, the protein isoform EqCXCL16S but not EqCXCL16R can function as an EAV cellular receptor. Although both molecules have equal chemoattractant potential, EqCXCL16S has significantly higher scavenger receptor and adhesion properties compared to EqCXCL16R.",2016 Dec 8,"['Sarkar, Sanjay', 'Bailey, Ernest', 'Go, Yun Young', 'Cook, R. Frank', 'Kalbfleisch, Ted', 'Eberth, John', 'Chelvarajan, R. Lakshman', 'Shuck, Kathleen M.', 'Artiushin, Sergey', 'Timoney, Peter J.', 'Balasuriya, Udeni B. R.']",PLoS Genet,,,True
dcf9e10df84c4439f2fb380b472de9ef2a6e55b8,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,True
4d61140dd3e58146f186edd06dba73088ec9cafa,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,False
4bb766c79e1d3c5605e0007a1a077813f6a67a8c,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,False
8e8e7ae819676089e49cb3eed7ae90e7d21ca68e,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,False
2f0b14bfd68f76cc8dd457afc675bbff500b8cd2,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,False
39d6d2420dada4c072e5f7122c40a3305f6c93f6,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,False
3deebe55bc1ee1b20e045ec3474c46faed3b38ee,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,False
b1e1e1ca56fc522da3ae2ffbfa4ade922af4e2fe,PMC,Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids,http://dx.doi.org/10.1371/journal.pone.0167651,PMC5145171,27930687,CC BY,"Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na(+)/K(+)-ATPase and Ca(2+)-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.",2016 Dec 8,"['Das, Jayanta Kumar', 'Das, Provas', 'Ray, Korak Kumar', 'Choudhury, Pabitra Pal', 'Jana, Siddhartha Sankar']",PLoS One,,,False
e319e1968d1de70b511e1b51fa5a69b3c75e41d4,PMC,Both Cerebral and Hematopoietic Deficiencies in CCR2 Result in Uncontrolled Herpes Simplex Virus Infection of the Central Nervous System in Mice,http://dx.doi.org/10.1371/journal.pone.0168034,PMC5145225,27930721,CC BY,"CCR2 is a chemokine receptor expressed on the surface of blood leukocytes, particularly «Ly6C(hi)» inflammatory monocytes and microglia. Signaling through this receptor is thought to influence the immune activity of microglia as well as monocytes egress from the bone marrow (BM) and their trafficking into the central nervous system (CNS) in several neurological diseases. During experimental herpes simplex virus 1 (HSV-1) encephalitis (HSE), CCR2 deficiency has been reported to exacerbate the outcome of the disease. However, the precise contribution of CCR2 expressed in cells of the CNS or peripheral monocytes in the protection against HSE remains unclear. To dissect the differential role of CCR2 during HSE, chimeric mice with receptor deficiency in the brain or blood cells were generated by transplanting wild-type (WT) C57BL/6 or CCR2(-/-) BM-derived cells in CCR2(-/-) (WT→CCR2(-/-)) and WT (CCR2(-/-)→WT) mice, respectively. Our results indicate that following intranasal infection with 1.2x10(6) plaque forming units of HSV-1, CCR2 deficiency in hematopoietic cells and, to a lesser extent, in CNS exacerbates the outcome of HSE. Mortality rates of CCR2(-/-) (71.4%) and CCR2(-/-)→WT (57.1%) mice were significantly higher than that of WT (15.3%; P<0.01 and P<0.05, respectively) but the difference did not reach statistical significance for WT→CCR2(-/-) animals (42.8%; P = 0.16). Both peripheral and CNS deficiencies in CCR2 resulted in increased infectious viral titers and wider dissemination of HSV antigens in the brain as well as an overproduction of inflammatory cytokines and chemokines including IL-1β, IL-6, CCL2, CCL3 and CCL5. Furthermore, CCR2 deficiency in the hematopoietic system altered monocytes egress from the BM and their recruitment to the CNS, which may contribute to the failure in HSV-1 containment. Collectively, these data suggest that CCR2 expressed on cells of CNS and especially on peripheral monocytes is important for the control of HSV-1 replication and inflammatory environment during experimental HSE.",2016 Dec 8,"['Menasria, Rafik', 'Canivet, Coraline', 'Piret, Jocelyne', 'Gosselin, Jean', 'Boivin, Guy']",PLoS One,,,True
9a60f844dc6dd4f0c5ddfc02fb970a04702eb388,PMC,Both Cerebral and Hematopoietic Deficiencies in CCR2 Result in Uncontrolled Herpes Simplex Virus Infection of the Central Nervous System in Mice,http://dx.doi.org/10.1371/journal.pone.0168034,PMC5145225,27930721,CC BY,"CCR2 is a chemokine receptor expressed on the surface of blood leukocytes, particularly «Ly6C(hi)» inflammatory monocytes and microglia. Signaling through this receptor is thought to influence the immune activity of microglia as well as monocytes egress from the bone marrow (BM) and their trafficking into the central nervous system (CNS) in several neurological diseases. During experimental herpes simplex virus 1 (HSV-1) encephalitis (HSE), CCR2 deficiency has been reported to exacerbate the outcome of the disease. However, the precise contribution of CCR2 expressed in cells of the CNS or peripheral monocytes in the protection against HSE remains unclear. To dissect the differential role of CCR2 during HSE, chimeric mice with receptor deficiency in the brain or blood cells were generated by transplanting wild-type (WT) C57BL/6 or CCR2(-/-) BM-derived cells in CCR2(-/-) (WT→CCR2(-/-)) and WT (CCR2(-/-)→WT) mice, respectively. Our results indicate that following intranasal infection with 1.2x10(6) plaque forming units of HSV-1, CCR2 deficiency in hematopoietic cells and, to a lesser extent, in CNS exacerbates the outcome of HSE. Mortality rates of CCR2(-/-) (71.4%) and CCR2(-/-)→WT (57.1%) mice were significantly higher than that of WT (15.3%; P<0.01 and P<0.05, respectively) but the difference did not reach statistical significance for WT→CCR2(-/-) animals (42.8%; P = 0.16). Both peripheral and CNS deficiencies in CCR2 resulted in increased infectious viral titers and wider dissemination of HSV antigens in the brain as well as an overproduction of inflammatory cytokines and chemokines including IL-1β, IL-6, CCL2, CCL3 and CCL5. Furthermore, CCR2 deficiency in the hematopoietic system altered monocytes egress from the BM and their recruitment to the CNS, which may contribute to the failure in HSV-1 containment. Collectively, these data suggest that CCR2 expressed on cells of CNS and especially on peripheral monocytes is important for the control of HSV-1 replication and inflammatory environment during experimental HSE.",2016 Dec 8,"['Menasria, Rafik', 'Canivet, Coraline', 'Piret, Jocelyne', 'Gosselin, Jean', 'Boivin, Guy']",PLoS One,,,False
efcd7d171bb51acf2ef0a631901900497957a3be,PMC,Relationship between hepcidin and oxidant/antioxidant status in calves with suspected neonatal septicemia,http://dx.doi.org/10.14202/vetworld.2016.1238-1241,PMC5146304,27956775,CC BY,"AIM: This study has been conducted for the purpose of determining serum hepcidin, total antioxidant status (TAS), total oxidant status (TOS), and Fe levels in calves with suspected neonatal septicemia before and after treatment and the clinical significance of hepcidin in calves with suspected neonatal septicemia. MATERIALS AND METHODS: The study material consisted of 15 calves of different ages and sexes brought to the Training, Research and Application Center at the Kafkas University Faculty of Veterinary Medicine with suspected neonatal septicemia. 8.5 mL of blood was drawn from the jugular vein of each animal into coagulant tubes before and after treatment for one-off biochemical analyses and centrifuged. After this, the serum was separated. Hepcidin, TAS, TOS, and Fe levels in the serum were measured. RESULTS: While pre-treatment hepcidin levels were 58.42±3.46 ng/mL, post-treatment levels were 46.87±2.98 ng/mL (p<0.05). Pre-treatment Fe levels were 60.13±7.27 µg/dl, while post-treatment levels were 83.1±8.09 µg/dl (p<0.05). The changes in the TAS and TOS levels were also found to be statistically significant. CONCLUSION: In light of the fact that hepcidin plays a role function in the regulation of Fe as well as the fact that Fe is a significant nutritional source for many microorganisms, it was concluded that hepcidin may play a significant role in nutritional immunity and the pathogenesis of diseases.",2016 Nov 14,"['Erkilic, E. E.', 'Erdogan, H. M.', 'Ogun, M.', 'Kirmizigul, A. H.', 'Gokce, E.', 'Kuru, M.', 'Kukurt, A.']",Vet World,,,True
b3fc1f4cd16b65fb6454b7c2705a95aee4419c46,PMC,Seroprevalence of Rotavirus infection in pig population of Arunachal Pradesh,http://dx.doi.org/10.14202/vetworld.2016.1300-1304,PMC5146314,27956785,CC BY,"AIM: This study was conducted to find out the seroprevalence of Rotavirus(RV) infection among the pig population of Arunachal Pradesh. MATERIALS AND METHODS: Serums samples were collected from piglets of age ranging from 1 week to 6 months and the sows associated with the piglets that were reared under organized and unorganized system of management in six different districts of Arunachal Pradesh. The prevalence of RV specific antibodies was detected using a polyclonal antibody-based indirect enzyme-linked immunosorbent assay (i-ELISA). RESULTS: The study revealed that out of 394 serum samples, 255 (64.72%) samples were found to be positive for RV-specific antibody in i-ELISA. Considering the samples from different districts, Papumpare district of Arunachal Pradesh showed highest numbers of seropositive animals (68.75%) followed by upper Subansiri (64.91%) while West Siang district showed lowest positivity rate (61.22%). CONCLUSION: As considerable seropositivity was recorded among pig population of Arunachal Pradesh in this study, there is urgent need to establish high-impact and cost-effective public health intervention tools, key among them being the introduction of strict hygiene practice and RV vaccination program, to greatly reduce the number of deaths due to diarrheal diseases. To the authors’ knowledge, this is the first report on the prevalence of RV infection from pigs of Arunachal Pradesh.",2016 Nov 27,"['Garam, G. B.', 'Bora, D. P.', 'Borah, B.', 'Bora, M.', 'Das, S. K.']",Vet World,,,True
c8c7265b3435763dfb209e8895c83e3cf8717a0f,PMC,Web-based infectious disease surveillance systems and public health perspectives: a systematic review,http://dx.doi.org/10.1186/s12889-016-3893-0,PMC5146908,27931204,CC BY,"BACKGROUND: Emerging and re-emerging infectious diseases are a significant public health concern, and early detection and immediate response is crucial for disease control. These challenges have led to the need for new approaches and technologies to reinforce the capacity of traditional surveillance systems for detecting emerging infectious diseases. In the last few years, the availability of novel web-based data sources has contributed substantially to infectious disease surveillance. This study explores the burgeoning field of web-based infectious disease surveillance systems by examining their current status, importance, and potential challenges. METHODS: A systematic review framework was applied to the search, screening, and analysis of web-based infectious disease surveillance systems. We searched PubMed, Web of Science, and Embase databases to extensively review the English literature published between 2000 and 2015. Eleven surveillance systems were chosen for evaluation according to their high frequency of application. Relevant terms, including newly coined terms, development and classification of the surveillance systems, and various characteristics associated with the systems were studied. RESULTS: Based on a detailed and informative review of the 11 web-based infectious disease surveillance systems, it was evident that these systems exhibited clear strengths, as compared to traditional surveillance systems, but with some limitations yet to be overcome. The major strengths of the newly emerging surveillance systems are that they are intuitive, adaptable, low-cost, and operated in real-time, all of which are necessary features of an effective public health tool. The most apparent potential challenges of the web-based systems are those of inaccurate interpretation and prediction of health status, and privacy issues, based on an individual’s internet activity. CONCLUSION: Despite being in a nascent stage with further modification needed, web-based surveillance systems have evolved to complement traditional national surveillance systems. This review highlights ways in which the strengths of existing systems can be maintained and weaknesses alleviated to implement optimal web surveillance systems. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-3893-0) contains supplementary material, which is available to authorized users.",2016 Dec 8,"['Choi, Jihye', 'Cho, Youngtae', 'Shim, Eunyoung', 'Woo, Hyekyung']",BMC Public Health,,,True
d7a83aa4ab9b3fb17d6fbb6d7fb5e71f3939135f,PMC,Unlocking bat immunology: establishment of Pteropus alecto bone marrow-derived dendritic cells and macrophages,http://dx.doi.org/10.1038/srep38597,PMC5146944,27934903,CC BY,"Bats carry and shed many emerging infectious disease agents including Ebola virus and SARS-like Coronaviruses, yet they rarely display clinical symptoms of infection. Bat epithelial or fibroblast cell lines were previously established to study the bat immune response against viral infection. However, the lack of professional immune cells such as dendritic cells (DC) and macrophages has greatly limited the significance of current investigations. Using Pteropus alecto (P. alecto) GM-CSF plus IL4, FLT3L and CSF-1, we successfully generated bat bone marrow-derived DC and macrophages. Cells with the phenotype, morphology and functional features of monocyte-derived DC, bona fide DC or macrophages were obtained in GM-CSF/IL4, FLT3L or CSF-1 cultures, respectively. The successful generation of the first bat bone marrow-derived immune cells paves the way to unlocking the immune mechanisms that confer host resilience to pathogens in bats.",2016 Dec 9,"['Zhou, Peng', 'Chionh, Yok Teng', 'Irac, Sergio Erdal', 'Ahn, Matae', 'Jia Ng, Justin Han', 'Fossum, Even', 'Bogen, Bjarne', 'Ginhoux, Florent', 'Irving, Aaron T', 'Dutertre, Charles-Antoine', 'Wang, Lin-Fa']",Sci Rep,,,True
4c437d37580c52301f130919d2d0f410efb2a1f9,PMC,Unlocking bat immunology: establishment of Pteropus alecto bone marrow-derived dendritic cells and macrophages,http://dx.doi.org/10.1038/srep38597,PMC5146944,27934903,CC BY,"Bats carry and shed many emerging infectious disease agents including Ebola virus and SARS-like Coronaviruses, yet they rarely display clinical symptoms of infection. Bat epithelial or fibroblast cell lines were previously established to study the bat immune response against viral infection. However, the lack of professional immune cells such as dendritic cells (DC) and macrophages has greatly limited the significance of current investigations. Using Pteropus alecto (P. alecto) GM-CSF plus IL4, FLT3L and CSF-1, we successfully generated bat bone marrow-derived DC and macrophages. Cells with the phenotype, morphology and functional features of monocyte-derived DC, bona fide DC or macrophages were obtained in GM-CSF/IL4, FLT3L or CSF-1 cultures, respectively. The successful generation of the first bat bone marrow-derived immune cells paves the way to unlocking the immune mechanisms that confer host resilience to pathogens in bats.",2016 Dec 9,"['Zhou, Peng', 'Chionh, Yok Teng', 'Irac, Sergio Erdal', 'Ahn, Matae', 'Jia Ng, Justin Han', 'Fossum, Even', 'Bogen, Bjarne', 'Ginhoux, Florent', 'Irving, Aaron T', 'Dutertre, Charles-Antoine', 'Wang, Lin-Fa']",Sci Rep,,,False
a3c3313dedf5e05ca7bc7388ff9471ff7032ef54,PMC,Ultrasensitive Detection of Porcine Epidemic Diarrhea Virus from Fecal Samples Using Functionalized Nanoparticles,http://dx.doi.org/10.1371/journal.pone.0167325,PMC5147876,27936019,CC BY,"Porcine epidemic diarrhea virus (PEDV) is the main causative agent of porcine diarrhea, which has resulted in devastating damage to swine industry and become a perplexed global problem. PEDV infection causes lesions and clinical symptoms, and infected pigs often succumb to severe dehydration. If there is not a timely and effective method to control its infection, PEDV will spread rapidly across the whole swine farm. Therefore, preclinical identification of PEDV is of great significance for preventing the outbreak and spread of this disease. In this study, a functionalized nanoparticles-based PCR method (UNDP-PCR) specific for PEDV was developed through systematic optimization of functionalized magnetic beads and gold nanoparticles which were further used to specifically enrich viral RNA from the lysate of PEDV stool samples, forming a MMPs-RNA-AuNPs complex. Then, oligonucleotides specific for PEDV coated on AuNPs were eluted from the complex and were further amplified and characterized by PCR. The detection limitation of the established UNDP-PCR method for PEDV was 25 copies in per gram PEDV stool samples, which is 400-fold more sensitive than conventional RT-PCR for stool samples. The UNDP-PCR for PEDV exhibited reliable reproducibility and high specificity, no cross-reaction was observed with other porcine viruses. In 153 preclinical fecal samples, the positive detection rate of UNDP-PCR specific for PEDV (30.72%) was much higher than that of conventional RT-PCR (5.88%) and SYBR Green real-time RT-PCR. In a word, this study provided a RNA extraction and transcription free, rapid and economical method for preclinical PEDV infection, which showed higher sensitivity, specificity and reproducibility, and exhibited application potency for evaluating viral loads of preclinical samples.",2016 Dec 9,"['Xing, Na', 'Guan, Xiaoxiao', 'An, Bin', 'Cui, Beibei', 'Wang, Zengguo', 'Wang, Xiaoya', 'Zhang, Xiujuan', 'Du, Qian', 'Zhao, Xiaomin', 'Huang, Yong', 'Tong, Dewen']",PLoS One,,,True
fc221d8af0a962a17778721217b1f9f914f353b4,PMC,Characterization of anti-MERS-CoV antibodies against various recombinant structural antigens of MERS-CoV in an imported case in China,http://dx.doi.org/10.1038/emi.2016.114,PMC5148018,27826140,CC BY,"The first imported case of Middle East respiratory syndrome (MERS) in China recently occurred, allowing for the characterization of antibody titers in a series of the patient's sera using the following methods based on recombinant viral structural antigens: inactivated MERS coronavirus (MERS-CoV) enzyme-linked immunosorbent assay (ELISA), recombinant MERS-CoV spike (S, or fragments of S) ELISA, nucleoprotein (NP) ELISA and MERS S pseudovirus particle-based neutralization test (ppNT). A longitudinal profile of the infection showed that seroconversion detected by ELISAs based on the recombinant extracellular domain, S, S1 and receptor-binding domain (RBD) antigens occurred as early as neutralizing antibodies were detected by the ppNT and earlier than antibodies were detected by the inactivated MERS-CoV and N-terminal domain (NTD) ELISAs. Antibodies detected by the NP ELISA occurred last. Strong correlations were found between the S1, RBD and NP ELISAs and the inactivated MERS-CoV ELISA. The S and RBD ELISAs were highly correlated with the commercial S1 ELISA. The S ELISA strongly correlated with the ppNT, although the MERS-CoV, S1, NTD and RBD ELISAs were also significantly correlated with the ppNT (P<0.001).",2016 Nov 9,"['Wang, Wenling', 'Wang, Huijuan', 'Deng, Yao', 'Song, Tie', 'Lan, Jiaming', 'Wu, Guizhen', 'Ke, Changwen', 'Tan, Wenjie']",Emerg Microbes Infect,,,True
b8cdd8c40d99073c91a2146a4ea2a2da5c04d808,PMC,Characterization of anti-MERS-CoV antibodies against various recombinant structural antigens of MERS-CoV in an imported case in China,http://dx.doi.org/10.1038/emi.2016.114,PMC5148018,27826140,CC BY,"The first imported case of Middle East respiratory syndrome (MERS) in China recently occurred, allowing for the characterization of antibody titers in a series of the patient's sera using the following methods based on recombinant viral structural antigens: inactivated MERS coronavirus (MERS-CoV) enzyme-linked immunosorbent assay (ELISA), recombinant MERS-CoV spike (S, or fragments of S) ELISA, nucleoprotein (NP) ELISA and MERS S pseudovirus particle-based neutralization test (ppNT). A longitudinal profile of the infection showed that seroconversion detected by ELISAs based on the recombinant extracellular domain, S, S1 and receptor-binding domain (RBD) antigens occurred as early as neutralizing antibodies were detected by the ppNT and earlier than antibodies were detected by the inactivated MERS-CoV and N-terminal domain (NTD) ELISAs. Antibodies detected by the NP ELISA occurred last. Strong correlations were found between the S1, RBD and NP ELISAs and the inactivated MERS-CoV ELISA. The S and RBD ELISAs were highly correlated with the commercial S1 ELISA. The S ELISA strongly correlated with the ppNT, although the MERS-CoV, S1, NTD and RBD ELISAs were also significantly correlated with the ppNT (P<0.001).",2016 Nov 9,"['Wang, Wenling', 'Wang, Huijuan', 'Deng, Yao', 'Song, Tie', 'Lan, Jiaming', 'Wu, Guizhen', 'Ke, Changwen', 'Tan, Wenjie']",Emerg Microbes Infect,,,False
fd63c849581a31e107d1f6af269c3cb152b565b5,PMC,Characterization of anti-MERS-CoV antibodies against various recombinant structural antigens of MERS-CoV in an imported case in China,http://dx.doi.org/10.1038/emi.2016.114,PMC5148018,27826140,CC BY,"The first imported case of Middle East respiratory syndrome (MERS) in China recently occurred, allowing for the characterization of antibody titers in a series of the patient's sera using the following methods based on recombinant viral structural antigens: inactivated MERS coronavirus (MERS-CoV) enzyme-linked immunosorbent assay (ELISA), recombinant MERS-CoV spike (S, or fragments of S) ELISA, nucleoprotein (NP) ELISA and MERS S pseudovirus particle-based neutralization test (ppNT). A longitudinal profile of the infection showed that seroconversion detected by ELISAs based on the recombinant extracellular domain, S, S1 and receptor-binding domain (RBD) antigens occurred as early as neutralizing antibodies were detected by the ppNT and earlier than antibodies were detected by the inactivated MERS-CoV and N-terminal domain (NTD) ELISAs. Antibodies detected by the NP ELISA occurred last. Strong correlations were found between the S1, RBD and NP ELISAs and the inactivated MERS-CoV ELISA. The S and RBD ELISAs were highly correlated with the commercial S1 ELISA. The S ELISA strongly correlated with the ppNT, although the MERS-CoV, S1, NTD and RBD ELISAs were also significantly correlated with the ppNT (P<0.001).",2016 Nov 9,"['Wang, Wenling', 'Wang, Huijuan', 'Deng, Yao', 'Song, Tie', 'Lan, Jiaming', 'Wu, Guizhen', 'Ke, Changwen', 'Tan, Wenjie']",Emerg Microbes Infect,,,False
979b57435d23b8a685e05afe29b41c6f7aa73336,PMC,Characterization of anti-MERS-CoV antibodies against various recombinant structural antigens of MERS-CoV in an imported case in China,http://dx.doi.org/10.1038/emi.2016.114,PMC5148018,27826140,CC BY,"The first imported case of Middle East respiratory syndrome (MERS) in China recently occurred, allowing for the characterization of antibody titers in a series of the patient's sera using the following methods based on recombinant viral structural antigens: inactivated MERS coronavirus (MERS-CoV) enzyme-linked immunosorbent assay (ELISA), recombinant MERS-CoV spike (S, or fragments of S) ELISA, nucleoprotein (NP) ELISA and MERS S pseudovirus particle-based neutralization test (ppNT). A longitudinal profile of the infection showed that seroconversion detected by ELISAs based on the recombinant extracellular domain, S, S1 and receptor-binding domain (RBD) antigens occurred as early as neutralizing antibodies were detected by the ppNT and earlier than antibodies were detected by the inactivated MERS-CoV and N-terminal domain (NTD) ELISAs. Antibodies detected by the NP ELISA occurred last. Strong correlations were found between the S1, RBD and NP ELISAs and the inactivated MERS-CoV ELISA. The S and RBD ELISAs were highly correlated with the commercial S1 ELISA. The S ELISA strongly correlated with the ppNT, although the MERS-CoV, S1, NTD and RBD ELISAs were also significantly correlated with the ppNT (P<0.001).",2016 Nov 9,"['Wang, Wenling', 'Wang, Huijuan', 'Deng, Yao', 'Song, Tie', 'Lan, Jiaming', 'Wu, Guizhen', 'Ke, Changwen', 'Tan, Wenjie']",Emerg Microbes Infect,,,False
3db2c3d613104b23711a28ea5f8f6a414d303376,PMC,Viral Agents Causing Acute Respiratory Infections in Children under Five: A Study from Eastern India,http://dx.doi.org/10.1155/2016/7235482,PMC5149672,28018433,CC BY,"Background. Acute respiratory infections (ARIs) are important cause of mortality and morbidity in children under five in developing country. Methods. This observational study was conducted over two-year period in a tertiary care teaching hospital of Eastern India. Nasal and throat swabs were collected, transported to the laboratory at 2–8°C in viral transport media, and then processed for detection of viruses using mono/multiplex real-time polymerase chain reaction. Results. A total of 300 children aged 2–60 months with ARIs were included. The most common age group affected with LRI was 2–12 mo and with URI was >12–60 mo. Viruses were detected in 248 cases. In URI, 77 were positive for single virus and 19 were positive for more than one virus; in LRI, 113 were positive for single virus and 12 were positive for more than one virus. The most common viruses isolated from URI cases were rhinovirus and adenovirus. The most common viruses isolated from LRI cases were respiratory syncytial virus and influenza virus. Most cases occurred in the months of January, December, and August. Conclusion. Viruses constitute a significant cause of ARI in children under five. RSV, ADV, RV, and IFV were the most prevalent viruses isolated.",2016 Nov 27,"['Mishra, Pravakar', 'Nayak, Lipika', 'Das, Rashmi Ranjan', 'Dwibedi, Bhagirathi', 'Singh, Amitabh']",Int J Pediatr,,,True
c9b4c7691175724573497c35ff6ac960a3208104,PMC,Glucose-6-phosphate dehydrogenase deficiency (G6PD) as a risk factor of male neonatal sepsis,,PMC5152609,27974910,CC BY,"Introduction.Neonatal sepsis is a disease process, which represents the systemic response of bacteria entering the bloodstream during the first 28 days of life. The prevalence of sepsis is higher in male infants than in females, but the exact cause is unknown. Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway, which leads to the production of NADPH. NADPH is required for the respiratory burst reaction in white blood cells (WBCs) to destroy microorganisms. The purpose of this study was to evaluate the prevalence of G6PD deficiency in neonates with sepsis. Materials and methods.This study was performed on 76 neonates with sepsis and 1214 normal neonates from February 2012 to November 2014 in the west of Iran. The G6PD deficiency status was determined by fluorescent spot test. WBCs number and neutrophils percentages were measured and compared in patients with and without G6PD deficiency. Results.The prevalence of the G6PD deficiency in neonates with sepsis was significantly higher compared to the control group (p=0.03). WBCs number and neutrophils percentages in G6PD deficient patients compared with patients without G6PD deficiency were decreased, but were not statistically significant (p=0.77 and p=0.86 respectively). Conclusions.G6PD deficiency is a risk factor of neonatal sepsis and also a justification for more male involvement in this disease. Therefore, newborn screening for this disorder is recommended.",2016 Jan-Mar,"['Rostami-Far, Z', 'Ghadiri, K', 'Rostami-Far, M', 'Shaveisi-Zadeh, F', 'Amiri, A', 'Rahimian Zarif, B']",J Med Life,,,True
f787f681d002077ccf52bcea98f4e708d71fd41d,PMC,The Effect of Contact Investigations and Public Health Interventions in the Control and Prevention of Measles Transmission: A Simulation Study,http://dx.doi.org/10.1371/journal.pone.0167160,PMC5152814,27941976,CC BY,"BACKGROUND: Measles cases continue to occur despite its elimination status in the United States. To control transmission, public health officials confirm the measles diagnosis, identify close contacts of infectious cases, deliver public health interventions (i.e., post-exposure prophylaxis) among those who are eligible, and follow-up with the close contacts to determine overall health outcomes. A stochastic network simulation of measles contact tracing was conducted using existing agent-based modeling software and a synthetic population with high levels of immunity in order to estimate the impact of different interventions in controlling measles transmission. METHODS AND FINDINGS: The synthetic population was created to simulate California`s population in terms of population demographics, household, workplace, school, and neighborhood characteristics using California Department of Finance 2010 census data. Parameters for the model were obtained from a review of the literature, California measles case surveillance data, and expert opinion. Eight different scenarios defined by the use of three different public health interventions were evaluated: (a) post-exposure measles, mumps, and rubella (MMR) vaccine, (b) post-exposure immune globulin (IG), and (c) voluntary isolation and home quarantine in the presence or absence of public health response delays. Voluntary isolation and home quarantine coupled with one or two other interventions had the greatest reduction in the number of secondary cases infected by the index case and the probability of escape situations (i.e., the outbreak continues after 90 days). CONCLUSIONS: Interrupting contact patterns via voluntary isolation and home quarantine are particularly important in reducing the number of secondary cases infected by the index case and the probability of uncontrolled outbreaks.",2016 Dec 12,"['Enanoria, Wayne T. A.', 'Liu, Fengchen', 'Zipprich, Jennifer', 'Harriman, Kathleen', 'Ackley, Sarah', 'Blumberg, Seth', 'Worden, Lee', 'Porco, Travis C.']",PLoS One,,,True
814ecf9043112382eaae1310c6359ddc70557bba,PMC,Assessment of Ebola virus disease preparedness in the WHO South-East Asia Region,http://dx.doi.org/10.2471/BLT.16.174441,PMC5153931,27994284,CC BY,"OBJECTIVE: To conduct assessments of Ebola virus disease preparedness in countries of the World Health Organization (WHO) South-East Asia Region. METHODS: Nine of 11 countries in the region agreed to be assessed. During February to November 2015 a joint team from WHO and ministries of health conducted 4–5 day missions to Bangladesh, Bhutan, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand and Timor-Leste. We collected information through guided discussions with senior technical leaders and visits to hospitals, laboratories and airports. We assessed each country’s Ebola virus disease preparedness on 41 tasks under nine key components adapted from the WHO Ebola preparedness checklist of January 2015. FINDINGS: Political commitment to Ebola preparedness was high in all countries. Planning was most advanced for components that had been previously planned or tested for influenza pandemics: multilevel and multisectoral coordination; multidisciplinary rapid response teams; public communication and social mobilization; drills in international airports; and training on personal protective equipment. Major vulnerabilities included inadequate risk assessment and risk communication; gaps in data management and analysis for event surveillance; and limited capacity in molecular diagnostic techniques. Many countries had limited planning for a surge of Ebola cases. Other tasks needing improvement included: advice to inbound travellers; adequate isolation rooms; appropriate infection control practices; triage systems in hospitals; laboratory diagnostic capacity; contact tracing; and danger pay to staff to ensure continuity of care. CONCLUSION: Joint assessment and feedback about the functionality of Ebola virus preparedness systems help countries strengthen their core capacities to meet the International Health Regulations.",2016 Dec 1,"['Vong, Sirenda', 'Samuel, Reuben', 'Gould, Philip', 'El Sakka, Hammam', 'Rana, Bardan J', 'Pinyowiwat, Vason', 'Bezbaruah, Supriya', 'Ofrin, Roderico']",Bull World Health Organ,,,True
4ba9bd26567dc15bc9a0abf88342604d62e336ab,PMC,Assay optimization for molecular detection of Zika virus,http://dx.doi.org/10.2471/BLT.16.175950,PMC5153932,27994281,CC BY,"OBJECTIVE: To examine the diagnostic performance of real-time reverse transcription (RT)-polymerase chain reaction (PCR) assays for Zika virus detection. METHODS: We compared seven published real-time RT–PCR assays and two new assays that we have developed. To determine the analytical sensitivity of each assay, we constructed a synthetic universal control ribonucleic acid (uncRNA) containing all of the assays’ target regions on one RNA strand and spiked human blood or urine with known quantities of African or Asian Zika virus strains. Viral loads in 33 samples from Zika virus-infected patients were determined by using one of the new assays. FINDINGS: Oligonucleotides of the published real-time RT–PCR assays, showed up to 10 potential mismatches with the Asian lineage causing the current outbreak, compared with 0 to 4 mismatches for the new assays. The 95% lower detection limit of the seven most sensitive assays ranged from 2.1 to 12.1 uncRNA copies/reaction. Two assays had lower sensitivities of 17.0 and 1373.3 uncRNA copies/reaction and showed a similar sensitivity when using spiked samples. The mean viral loads in samples from Zika virus-infected patients were 5 × 10(4) RNA copies/mL of blood and 2 × 10(4) RNA copies/mL of urine. CONCLUSION: We provide reagents and updated protocols for Zika virus detection suitable for the current outbreak strains. Some published assays might be unsuitable for Zika virus detection, due to the limited sensitivity and potential incompatibility with some strains. Viral concentrations in the clinical samples were close to the technical detection limit, suggesting that the use of insensitive assays will cause false-negative results.",2016 Dec 1,"['Corman, Victor M', 'Rasche, Andrea', 'Baronti, Cecile', 'Aldabbagh, Souhaib', 'Cadar, Daniel', 'Reusken, Chantal BEM', 'Pas, Suzan D', 'Goorhuis, Abraham', 'Schinkel, Janke', 'Molenkamp, Richard', 'Kümmerer, Beate M', 'Bleicker, Tobias', 'Brünink, Sebastian', 'Eschbach-Bludau, Monika', 'Eis-Hübinger, Anna M', 'Koopmans, Marion P', 'Schmidt-Chanasit, Jonas', 'Grobusch, Martin P', 'de Lamballerie, Xavier', 'Drosten, Christian', 'Drexler, Jan Felix']",Bull World Health Organ,,,True
8029841b3e6b0267188b9c527b0e02dc472b9fdc,PMC,Single Fluorescence Channel-based Multiplex Detection of Avian Influenza Virus by Quantitative PCR with Intercalating Dye,http://dx.doi.org/10.1038/srep11479,PMC5155576,26088868,CC BY,"Since its invention in 1985 the polymerase chain reaction (PCR) has become a well-established method for amplification and detection of segments of double-stranded DNA. Incorporation of fluorogenic probe or DNA intercalating dyes (such as SYBR Green) into the PCR mixture allowed real-time reaction monitoring and extraction of quantitative information (qPCR). Probes with different excitation spectra enable multiplex qPCR of several DNA segments using multi-channel optical detection systems. Here we show multiplex qPCR using an economical EvaGreen-based system with single optical channel detection. Previously reported non quantitative multiplex real-time PCR techniques based on intercalating dyes were conducted once the PCR is completed by performing melting curve analysis (MCA). The technique presented in this paper is both qualitative and quantitative as it provides information about the presence of multiple DNA strands as well as the number of starting copies in the tested sample. Besides important internal control, multiplex qPCR also allows detecting concentrations of more than one DNA strand within the same sample. Detection of the avian influenza virus H7N9 by PCR is a well established method. Multiplex qPCR greatly enhances its specificity as it is capable of distinguishing both haemagglutinin (HA) and neuraminidase (NA) genes as well as their ratio.",2015 Jun 19,"['Ahberg, Christian D.', 'Manz, Andreas', 'Neuzil, Pavel']",Sci Rep,,,True
a274eabdee76dfe956dc3fdcaa5a105e8fd465bd,PMC,The ecology and adaptive evolution of influenza A interspecies transmission,http://dx.doi.org/10.1111/irv.12412,PMC5155642,27426214,CC BY,"Since 2013, there have been several alarming influenza‐related events; the spread of highly pathogenic avian influenza H5 viruses into North America, the detection of H10N8 and H5N6 zoonotic infections, the ongoing H7N9 infections in China and the continued zoonosis of H5N1 viruses in parts of Asia and the Middle East. The risk of a new influenza pandemic increases with the repeated interspecies transmission events that facilitate reassortment between animal influenza strains; thus, it is of utmost importance to understand the factors involved that promote or become a barrier to cross‐species transmission of Influenza A viruses (IAVs). Here, we provide an overview of the ecology and evolutionary adaptations of IAVs, with a focus on a review of the molecular factors that enable interspecies transmission of the various virus gene segments.",2017 Jan 8,"['Joseph, Udayan', 'Su, Yvonne C. F.', 'Vijaykrishna, Dhanasekaran', 'Smith, Gavin J. D.']",Influenza Other Respir Viruses,,,True
0c2489ea506fea5ac57b464c2a99f893cc867ff3,PMC,Epidemiology and clinical characteristics of respiratory syncytial virus infections among children and adults in Mexico,http://dx.doi.org/10.1111/irv.12414,PMC5155644,27439650,CC BY,"BACKGROUND: Respiratory syncytial virus (RSV) is a leading etiological agent of acute respiratory tract infections and hospitalizations in children. However, little information is available regarding RSV infections in Latin American countries, particularly among adult patients. OBJECTIVE: To describe the epidemiology of RSV infection and to analyze the factors associated with severe infections in children and adults in Mexico. METHODS: Patients ≥1 month old, who presented with an influenza‐like illness (ILI) to six hospitals in Mexico, were eligible for participation in the study. Multiplex reverse‐transcriptase polymerase chain reaction identified viral pathogens in nasal swabs from 5629 episodes of ILI. Patients in whom RSV was detected were included in this report. RESULTS: Respiratory syncytial virus was detected in 399 children and 171 adults. RSV A was detected in 413 cases and RSV B in 163, including six patients who had coinfection with both subtypes; 414 (72.6%) patients required hospital admission, including 96 (16.8%) patients that required admission to the intensive care unit. Coinfection with one or more respiratory pathogens other than RSV was detected in 159 cases. Young age (in children) and older age (in adults) as well as the presence of some underlying conditions were associated with more severe disease. CONCLUSIONS: This study confirms that RSV is an important respiratory pathogen in children in Mexico. In addition, a substantial number of cases in adults were also detected highlighting the relevance of this virus in all ages. It is important to identify subjects at high risk of complications who may benefit from current or future preventive interventions.",2017 Jan 18,"['Gamiño‐Arroyo, Ana E.', 'Moreno‐Espinosa, Sarbelio', 'Llamosas‐Gallardo, Beatriz', 'Ortiz‐Hernández, Ana A.', 'Guerrero, M. Lourdes', 'Galindo‐Fraga, Arturo', 'Galán‐Herrera, Juan F.', 'Prado‐Galbarro, Francisco J.', 'Beigel, John H.', 'Ruiz‐Palacios, Guillermo M.', 'Noyola, Daniel E.', None]",Influenza Other Respir Viruses,,,True
2b84b189357f940efd105bcfe6e45ea14bdcc95c,PMC,CONSISE statement on the reporting of Seroepidemiologic Studies for influenza (ROSES‐I statement): an extension of the STROBE statement,http://dx.doi.org/10.1111/irv.12411,PMC5155648,27417916,CC BY,"BACKGROUND: Population‐based serologic studies are a vital tool for understanding the epidemiology of influenza and other respiratory viruses, including the early assessment of the transmissibility and severity of the 2009 influenza pandemic, and Middle East respiratory syndrome coronavirus. However, interpretation of the results of serologic studies has been hampered by the diversity of approaches and the lack of standardized methods and reporting. OBJECTIVE: The objective of the CONSISE ROSES ‐I statement was to improve the quality and transparency of reporting of influenza seroepidemiologic studies and facilitate the assessment of the validity and generalizability of published results. METHODS: The ROSES‐I statement was developed as an expert consensus of the CONSISE epidemiology and laboratory working groups. The recommendations are presented in the familiar format of a reporting guideline. Because seroepidemiologic studies are a specific type of observational epidemiology study, the ROSES‐I statement is built upon the STROBE guidelines. As such, the ROSES‐I statement should be seen as an extension of the STROBE guidelines. RESULTS: The ROSES ‐I statement presents 42 items that can be used as a checklist of the information that should be included in the results of published seroepidemiologic studies, and which can also serve as a guide to the items that need to be considered during study design and implementation. CONCLUSIONS: We hope that the ROSES‐I statement will contribute to improving the quality of reporting of seroepidemiologic studies.",2017 Jan 9,"['Horby, Peter W.', 'Laurie, Karen L.', 'Cowling, Benjamin J.', 'Engelhardt, Othmar G.', 'Sturm‐Ramirez, Katharine', 'Sanchez, Jose L.', 'Katz, Jacqueline M.', 'Uyeki, Timothy M.', 'Wood, John', 'Van Kerkhove, Maria D.', None]",Influenza Other Respir Viruses,,,True
7bc3103f71aaffbda7cdeb61603f12ded3194ab5,PMC,Cross‐sectional survey and surveillance for influenza viruses and MERS‐CoV among Egyptian pilgrims returning from Hajj during 2012‐2015,http://dx.doi.org/10.1111/irv.12429,PMC5155725,27603034,CC BY,"BACKGROUND: Approximately 80 000 Egyptians participate in Hajj pilgrimage annually. The purpose of this study was to estimate influenza virus and MERS‐CoV prevalence among Egyptian pilgrims returning from Hajj. STUDY: A cross‐sectional survey among 3 364 returning Egyptian pilgrims from 2012 to 2015 was conducted. Nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected from all participants. Sputum specimens were collected from participants with respiratory symptoms and productive cough at the time of their interview. Specimens were tested for influenza viruses, and a convenience sample of NP/OP specimens was tested for MERS‐CoV. Thirty percent of participants met the case definition for influenza‐like illness (ILI), 14% tested positive for influenza viruses, and none tested positive for MERS‐CoV. Self‐reported influenza vaccination was 20%. CONCLUSIONS: High prevalence of reported ILI during pilgrimage and confirmed influenza virus on return from pilgrimage suggest a continued need for influenza prevention strategies for Egyptian Hajj pilgrims. An evaluation of the Ministry of Health and Population's current risk communication campaigns to increase influenza vaccine use among pilgrims may help identify strategies to improve vaccine coverage.",2017 Jan 11,"['Refaey, Samir', 'Amin, Marwa Mohamed', 'Roguski, Katherine', 'Azziz‐Baumgartner, Eduardo', 'Uyeki, Timothy M.', 'Labib, Manal', 'Kandeel, Amr']",Influenza Other Respir Viruses,,,True
788295abb7003fc90fdadb54283b664724c83b33,PMC,The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.01721-16,PMC5156301,27965448,CC BY,"ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.",2016 Dec 13,"['Fehr, Anthony R.', 'Channappanavar, Rudragouda', 'Jankevicius, Gytis', 'Fett, Craig', 'Zhao, Jincun', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Ahel, Ivan', 'Perlman, Stanley']",mBio,,,True
49e8d990cb97517904b72c77aa457ee4564e6779,PMC,The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.01721-16,PMC5156301,27965448,CC BY,"ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.",2016 Dec 13,"['Fehr, Anthony R.', 'Channappanavar, Rudragouda', 'Jankevicius, Gytis', 'Fett, Craig', 'Zhao, Jincun', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Ahel, Ivan', 'Perlman, Stanley']",mBio,,,False
76ac304a8bf37f61466085482cee345aae6dd1f4,PMC,The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.01721-16,PMC5156301,27965448,CC BY,"ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.",2016 Dec 13,"['Fehr, Anthony R.', 'Channappanavar, Rudragouda', 'Jankevicius, Gytis', 'Fett, Craig', 'Zhao, Jincun', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Ahel, Ivan', 'Perlman, Stanley']",mBio,,,False
24ffda519bebb75d54ef12eea8759ca4be138262,PMC,The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.01721-16,PMC5156301,27965448,CC BY,"ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.",2016 Dec 13,"['Fehr, Anthony R.', 'Channappanavar, Rudragouda', 'Jankevicius, Gytis', 'Fett, Craig', 'Zhao, Jincun', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Ahel, Ivan', 'Perlman, Stanley']",mBio,,,False
a15edc2d862771e530d404425b5910b328857db9,PMC,The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.01721-16,PMC5156301,27965448,CC BY,"ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.",2016 Dec 13,"['Fehr, Anthony R.', 'Channappanavar, Rudragouda', 'Jankevicius, Gytis', 'Fett, Craig', 'Zhao, Jincun', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Ahel, Ivan', 'Perlman, Stanley']",mBio,,,False
6ac1bb3e9bac1d430c9d492be6664a9443e52cea,PMC,The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.01721-16,PMC5156301,27965448,CC BY,"ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.",2016 Dec 13,"['Fehr, Anthony R.', 'Channappanavar, Rudragouda', 'Jankevicius, Gytis', 'Fett, Craig', 'Zhao, Jincun', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Ahel, Ivan', 'Perlman, Stanley']",mBio,,,False
494420ff931d8a803437b8830be805b57db29969,PMC,The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection,http://dx.doi.org/10.1128/mBio.01721-16,PMC5156301,27965448,CC BY,"ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.",2016 Dec 13,"['Fehr, Anthony R.', 'Channappanavar, Rudragouda', 'Jankevicius, Gytis', 'Fett, Craig', 'Zhao, Jincun', 'Athmer, Jeremiah', 'Meyerholz, David K.', 'Ahel, Ivan', 'Perlman, Stanley']",mBio,,,False
5a073b51c60bf4d599c2e5bfe236bd11abf07daa,PMC,Foot-and-mouth disease virus replicates independently of phosphatidylinositol 4-phosphate and type III phosphatidylinositol 4-kinases,http://dx.doi.org/10.1099/jgv.0.000485,PMC5156328,27093462,CC BY,"Picornaviruses form replication complexes in association with membranes in structures called replication organelles. Common themes to emerge from studies of picornavirus replication are the need for cholesterol and phosphatidylinositol 4-phosphate (PI4P). In infected cells, type III phosphatidylinositol 4-kinases (PI4KIIIs) generate elevated levels of PI4P, which is then exchanged for cholesterol at replication organelles. For the enteroviruses, replication organelles form at Golgi membranes in a process that utilizes PI4KIIIβ. Other picornaviruses, for example the cardioviruses, are believed to initiate replication at the endoplasmic reticulum and subvert PI4KIIIα to generate PI4P. Here we investigated the role of PI4KIII in foot-and-mouth disease virus (FMDV) replication. Our results showed that, in contrast to the enteroviruses and the cardioviruses, FMDV replication does not require PI4KIII (PI4KIIIα and PI4KIIIβ), and PI4P levels do not increase in FMDV-infected cells and PI4P is not seen at replication organelles. These results point to a unique requirement towards lipids at the FMDV replication membranes.",2016 Aug,"['Berryman, Stephen', 'Moffat, Katy', 'Harak, Christian', 'Lohmann, Volker', 'Jackson, Terry']",J Gen Virol,,,True
9978c4e80ad9c6c31863571080b871eb4c412168,PMC,Foot-and-mouth disease virus replicates independently of phosphatidylinositol 4-phosphate and type III phosphatidylinositol 4-kinases,http://dx.doi.org/10.1099/jgv.0.000485,PMC5156328,27093462,CC BY,"Picornaviruses form replication complexes in association with membranes in structures called replication organelles. Common themes to emerge from studies of picornavirus replication are the need for cholesterol and phosphatidylinositol 4-phosphate (PI4P). In infected cells, type III phosphatidylinositol 4-kinases (PI4KIIIs) generate elevated levels of PI4P, which is then exchanged for cholesterol at replication organelles. For the enteroviruses, replication organelles form at Golgi membranes in a process that utilizes PI4KIIIβ. Other picornaviruses, for example the cardioviruses, are believed to initiate replication at the endoplasmic reticulum and subvert PI4KIIIα to generate PI4P. Here we investigated the role of PI4KIII in foot-and-mouth disease virus (FMDV) replication. Our results showed that, in contrast to the enteroviruses and the cardioviruses, FMDV replication does not require PI4KIII (PI4KIIIα and PI4KIIIβ), and PI4P levels do not increase in FMDV-infected cells and PI4P is not seen at replication organelles. These results point to a unique requirement towards lipids at the FMDV replication membranes.",2016 Aug,"['Berryman, Stephen', 'Moffat, Katy', 'Harak, Christian', 'Lohmann, Volker', 'Jackson, Terry']",J Gen Virol,,,False
7f2079d6e5244be0e38c55fe08a1c1672ab645fb,PMC,Viral factors in influenza pandemic risk assessment,http://dx.doi.org/10.7554/eLife.18491,PMC5156527,27834632,CC0,"The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans. To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human. Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus. The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures. We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk. DOI: http://dx.doi.org/10.7554/eLife.18491.001",,"['Lipsitch, Marc', 'Barclay, Wendy', 'Raman, Rahul', 'Russell, Charles J', 'Belser, Jessica A', 'Cobey, Sarah', 'Kasson, Peter M', 'Lloyd-Smith, James O', 'Maurer-Stroh, Sebastian', 'Riley, Steven', 'Beauchemin, Catherine AA', 'Bedford, Trevor', 'Friedrich, Thomas C', 'Handel, Andreas', 'Herfst, Sander', 'Murcia, Pablo R', 'Roche, Benjamin', 'Wilke, Claus O', 'Russell, Colin A']",eLife.; 5:e18491,,,True
3455e9fd57dea013498de20c236c15b7bf19b424,PMC,A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses,http://dx.doi.org/10.1128/mSphere.00275-16,PMC5156671,27981236,CC BY,"The H1 subtype of influenza A viruses (IAVs) has been circulating in swine since the 1918 human influenza pandemic. Over time, and aided by further introductions from nonswine hosts, swine H1 viruses have diversified into three genetic lineages. Due to limited global data, these H1 lineages were named based on colloquial context, leading to a proliferation of inconsistent regional naming conventions. In this study, we propose rigorous phylogenetic criteria to establish a globally consistent nomenclature of swine H1 virus hemagglutinin (HA) evolution. These criteria applied to a data set of 7,070 H1 HA sequences led to 28 distinct clades as the basis for the nomenclature. We developed and implemented a web-accessible annotation tool that can assign these biologically informative categories to new sequence data. The annotation tool assigned the combined data set of 7,070 H1 sequences to the correct clade more than 99% of the time. Our analyses indicated that 87% of the swine H1 viruses from 2010 to the present had HAs that belonged to 7 contemporary cocirculating clades. Our nomenclature and web-accessible classification tool provide an accurate method for researchers, diagnosticians, and health officials to assign clade designations to HA sequences. The tool can be updated readily to track evolving nomenclature as new clades emerge, ensuring continued relevance. A common global nomenclature facilitates comparisons of IAVs infecting humans and pigs, within and between regions, and can provide insight into the diversity of swine H1 influenza virus and its impact on vaccine strain selection, diagnostic reagents, and test performance, thereby simplifying communication of such data. IMPORTANCE A fundamental goal in the biological sciences is the definition of groups of organisms based on evolutionary history and the naming of those groups. For influenza A viruses (IAVs) in swine, understanding the hemagglutinin (HA) genetic lineage of a circulating strain aids in vaccine antigen selection and allows for inferences about vaccine efficacy. Previous reporting of H1 virus HA in swine relied on colloquial names, frequently with incriminating and stigmatizing geographic toponyms, making comparisons between studies challenging. To overcome this, we developed an adaptable nomenclature using measurable criteria for historical and contemporary evolutionary patterns of H1 global swine IAVs. We also developed a web-accessible tool that classifies viruses according to this nomenclature. This classification system will aid agricultural production and pandemic preparedness through the identification of important changes in swine IAVs and provides terminology enabling discussion of swine IAVs in a common context among animal and human health initiatives.",2016 Dec 14,"['Anderson, Tavis K.', 'Macken, Catherine A.', 'Lewis, Nicola S.', 'Scheuermann, Richard H.', 'Van Reeth, Kristien', 'Brown, Ian H.', 'Swenson, Sabrina L.', 'Simon, Gaëlle', 'Saito, Takehiko', 'Berhane, Yohannes', 'Ciacci-Zanella, Janice', 'Pereda, Ariel', 'Davis, C. Todd', 'Donis, Ruben O.', 'Webby, Richard J.', 'Vincent, Amy L.']",mSphere,,,True
36752c93b63eeae6c380c8fa56aa2080b695830c,PMC,Porcine Epidemic Diarrhea Virus Shedding and Antibody Response in Swine Farms: A Longitudinal Study,http://dx.doi.org/10.3389/fmicb.2016.02009,PMC5156881,28018330,CC BY,"The porcine epidemic diarrhea virus (PEDV) causes an acute and highly contagious enteric disease characterized by severe enteritis, vomiting, watery diarrhea, and a high mortality rate in seronegative neonatal piglets. In the last few years, PED had a large economic impact on the swine industries in Asia and the US, and in 2014, the PEDV also re-emerged in Europe. Two main PEDV variants circulate worldwide but only the S INDEL variant, considered a mild strain, is spreading in Europe. To gain insights into the pathogenicity of this variant, its viral load and temporal shedding pattern were evaluated in piglets from infected farms. Quantitative real-time PCR (qPCR) targeting the spike gene, was validated according to the minimum information for quantitative real-time PCR experiments guidelines. The qPCR was applied to longitudinal studies conducted in four swine farms naturally infected with the PEDV S INDEL variant. Clinical data, fecal swabs, and blood samples were collected from 103 piglets at 15–30-day intervals for 2–5 months. On all four farms, diarrhea was observed in sows during gestation and in farrowing units, and the mortality rates of piglets were 18, 25, 30, and 35%. Different clinical pictures (0-50% of diarrhea positivity), viral titer levels (mean 5.3-7.2 log(10) genome copies/mL), and antibody conditions (30-80% of positivity) were registered among sows on the four farms. The percentage of qPCR positive piglets varied greatly from the beginning (63–100%) to the end (0%) of the infection course. Clinical signs were present in 96% of the qPCR positive animals. Viral loads ranged from 8.5 log(10) to 4 log(10) genome copies/mL in suckling pigs at 3–6 days of age and were not statistically different among farms, despite the different patterns observed in sows. After 2–3 weeks, only a few piglets still showed detectable viral levels and clinical signs, and they developed antibody responses. Moreover, co-infections with other pathogens and biosecurity procedures limiting the circulation of the virus could have influenced the severity of PED infection. QPCR and clinical data were useful in understanding the dynamics of PEDV infections and, therefore, in implementing appropriate control measures.",2016 Dec 15,"['Bertasio, Cristina', 'Giacomini, Enrico', 'Lazzaro, Massimiliano', 'Perulli, Simona', 'Papetti, Alice', 'Lavazza, Antonio', 'Lelli, Davide', 'Alborali, Giovanni', 'Boniotti, Maria B.']",Front Microbiol,,,False
2f19514c3e82b60132c6170ba732029ade5827a2,PMC,Porcine Epidemic Diarrhea Virus Shedding and Antibody Response in Swine Farms: A Longitudinal Study,http://dx.doi.org/10.3389/fmicb.2016.02009,PMC5156881,28018330,CC BY,"The porcine epidemic diarrhea virus (PEDV) causes an acute and highly contagious enteric disease characterized by severe enteritis, vomiting, watery diarrhea, and a high mortality rate in seronegative neonatal piglets. In the last few years, PED had a large economic impact on the swine industries in Asia and the US, and in 2014, the PEDV also re-emerged in Europe. Two main PEDV variants circulate worldwide but only the S INDEL variant, considered a mild strain, is spreading in Europe. To gain insights into the pathogenicity of this variant, its viral load and temporal shedding pattern were evaluated in piglets from infected farms. Quantitative real-time PCR (qPCR) targeting the spike gene, was validated according to the minimum information for quantitative real-time PCR experiments guidelines. The qPCR was applied to longitudinal studies conducted in four swine farms naturally infected with the PEDV S INDEL variant. Clinical data, fecal swabs, and blood samples were collected from 103 piglets at 15–30-day intervals for 2–5 months. On all four farms, diarrhea was observed in sows during gestation and in farrowing units, and the mortality rates of piglets were 18, 25, 30, and 35%. Different clinical pictures (0-50% of diarrhea positivity), viral titer levels (mean 5.3-7.2 log(10) genome copies/mL), and antibody conditions (30-80% of positivity) were registered among sows on the four farms. The percentage of qPCR positive piglets varied greatly from the beginning (63–100%) to the end (0%) of the infection course. Clinical signs were present in 96% of the qPCR positive animals. Viral loads ranged from 8.5 log(10) to 4 log(10) genome copies/mL in suckling pigs at 3–6 days of age and were not statistically different among farms, despite the different patterns observed in sows. After 2–3 weeks, only a few piglets still showed detectable viral levels and clinical signs, and they developed antibody responses. Moreover, co-infections with other pathogens and biosecurity procedures limiting the circulation of the virus could have influenced the severity of PED infection. QPCR and clinical data were useful in understanding the dynamics of PEDV infections and, therefore, in implementing appropriate control measures.",2016 Dec 15,"['Bertasio, Cristina', 'Giacomini, Enrico', 'Lazzaro, Massimiliano', 'Perulli, Simona', 'Papetti, Alice', 'Lavazza, Antonio', 'Lelli, Davide', 'Alborali, Giovanni', 'Boniotti, Maria B.']",Front Microbiol,,,False
68c82e3e364e4f32d14a480538ccc8d0b5d5802c,PMC,Porcine Epidemic Diarrhea Virus Shedding and Antibody Response in Swine Farms: A Longitudinal Study,http://dx.doi.org/10.3389/fmicb.2016.02009,PMC5156881,28018330,CC BY,"The porcine epidemic diarrhea virus (PEDV) causes an acute and highly contagious enteric disease characterized by severe enteritis, vomiting, watery diarrhea, and a high mortality rate in seronegative neonatal piglets. In the last few years, PED had a large economic impact on the swine industries in Asia and the US, and in 2014, the PEDV also re-emerged in Europe. Two main PEDV variants circulate worldwide but only the S INDEL variant, considered a mild strain, is spreading in Europe. To gain insights into the pathogenicity of this variant, its viral load and temporal shedding pattern were evaluated in piglets from infected farms. Quantitative real-time PCR (qPCR) targeting the spike gene, was validated according to the minimum information for quantitative real-time PCR experiments guidelines. The qPCR was applied to longitudinal studies conducted in four swine farms naturally infected with the PEDV S INDEL variant. Clinical data, fecal swabs, and blood samples were collected from 103 piglets at 15–30-day intervals for 2–5 months. On all four farms, diarrhea was observed in sows during gestation and in farrowing units, and the mortality rates of piglets were 18, 25, 30, and 35%. Different clinical pictures (0-50% of diarrhea positivity), viral titer levels (mean 5.3-7.2 log(10) genome copies/mL), and antibody conditions (30-80% of positivity) were registered among sows on the four farms. The percentage of qPCR positive piglets varied greatly from the beginning (63–100%) to the end (0%) of the infection course. Clinical signs were present in 96% of the qPCR positive animals. Viral loads ranged from 8.5 log(10) to 4 log(10) genome copies/mL in suckling pigs at 3–6 days of age and were not statistically different among farms, despite the different patterns observed in sows. After 2–3 weeks, only a few piglets still showed detectable viral levels and clinical signs, and they developed antibody responses. Moreover, co-infections with other pathogens and biosecurity procedures limiting the circulation of the virus could have influenced the severity of PED infection. QPCR and clinical data were useful in understanding the dynamics of PEDV infections and, therefore, in implementing appropriate control measures.",2016 Dec 15,"['Bertasio, Cristina', 'Giacomini, Enrico', 'Lazzaro, Massimiliano', 'Perulli, Simona', 'Papetti, Alice', 'Lavazza, Antonio', 'Lelli, Davide', 'Alborali, Giovanni', 'Boniotti, Maria B.']",Front Microbiol,,,True
92af993d895fbe5ec7c8ba631624b1a66171a7c8,PMC,Screening and Identification of APOC1 as a Novel Potential Biomarker for Differentiate of Mycoplasma pneumoniae in Children,http://dx.doi.org/10.3389/fmicb.2016.01961,PMC5156883,28018301,CC BY,"Background: Although Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia (CAP) in children, the currently used diagnostic methods are not optimal. Proteomics is increasingly being used to study the biomarkers of infectious diseases. Methods: Label-free quantitative proteomics and liquid chromatography-mass/mass spectrometry were used to analyze the fold change of protein expression in plasma of children with MP pneumonia (MPP), infectious disease control (IDC), and healthy control (HC) groups. Selected proteins that can distinguish MPP from HC and IDC were further validated by enzyme-linked immunosorbent assay (ELISA). Results: After multivariate analyses, 27 potential plasma biomarkers were identified to be expressed differently among child MPP, HC, and IDC groups. Among these proteins, SERPINA3, APOC1, ANXA6, KNTC1, and CFLAR were selected for ELISA verification. SERPINA3, APOC1, and CFLAR levels were significantly different among the three groups and the ratios were consistent with the trends of proteomics results. A comparison of MPP patients and HC showed APOC1 had the largest area under the curve (AUC) of 0.853, with 77.6% sensitivity and 81.1% specificity. When APOC1 levels were compared between MPP and IDC patients, it also showed a relatively high AUC of 0.882, with 77.6% sensitivity and 85.3% specificity. Conclusion: APOC1 is a potential biomarker for the rapid and noninvasive diagnosis of MPP in children. The present finding may offer new insights into the pathogenesis and biomarker selection of MPP in children.",2016 Dec 15,"['Li, Jieqiong', 'Sun, Lin', 'Xu, Fang', 'Qi, Hui', 'Shen, Chen', 'Jiao, Weiwei', 'Xiao, Jing', 'Li, Qinjing', 'Xu, Baoping', 'Shen, Adong']",Front Microbiol,,,True
2c332ca9f08d552ef49e6945655e9059e82ba13d,PMC,Expression Cloning and Production of Human Heavy-Chain-Only Antibodies from Murine Transgenic Plasma Cells,http://dx.doi.org/10.3389/fimmu.2016.00619,PMC5165034,28066429,CC BY,"Several technologies have been developed to isolate human antibodies against different target antigens as a source of potential therapeutics, including hybridoma technology, phage and yeast display systems. For conventional antibodies, this involves either random pairing of VH and variable light (VL) domains in combinatorial display libraries or isolation of cognate pairs of VH and VL domains from human B cells or from transgenic mice carrying human immunoglobulin loci followed by single-cell sorting, single-cell RT-PCR, and bulk cloning of isolated natural VH–VL pairs. Heavy-chain-only antibodies (HCAbs) that naturally occur in camelids require only heavy immunoglobulin chain cloning. Here, we present an automatable novel, high-throughput technology for rapid direct cloning and production of fully human HCAbs from sorted population of transgenic mouse plasma cells carrying a human HCAb locus. Utility of the technique is demonstrated by isolation of diverse sets of sequence unique, soluble, high-affinity influenza A strain X-31 hemagglutinin-specific HCAbs.",2016 Dec 19,"['Drabek, Dubravka', 'Janssens, Rick', 'de Boer, Ernie', 'Rademaker, Rik', 'Kloess, Johannes', 'Skehel, John', 'Grosveld, Frank']",Front Immunol,,,True
5dc1559b4274012d8152b7c5f4ca0d637e8b62fa,PMC,Modernising epidemic science: enabling patient-centred research during epidemics,http://dx.doi.org/10.1186/s12916-016-0760-x,PMC5165716,27989237,CC BY,"BACKGROUND: Emerging and epidemic infectious disease outbreaks are a significant public health problem and global health security threat. As an outbreak begins, epidemiological investigations and traditional public health responses are generally mounted very quickly. However, patient-centred research is usually not prioritised when planning and enacting the response. Instead, the clinical research response occurs subsequent to and separate from the public health response, and is inadequate for evidence-based decision-making at the bedside or in the offices of public health policymakers. DISCUSSION: The deficiencies of the clinical research response to severe acute respiratory syndrome, pandemic influenza, Middle East respiratory syndrome coronavirus and Ebola virus demonstrate that current research models do not adequately inform and improve the quality of clinical care or public health response. Three suggestions for improvements are made. First, integrate the data and sample collection needs for clinical and public health decision-making within a unified framework, combined with a risk-based, rather than a discipline-based, approach to ethical review and consent. Second, develop clinical study methods and tools that are specifically designed to meet the epidemiological and contextual challenges of emerging and epidemic infectious diseases. Third, invest in investigator-led clinical research networks that are primed and incentivised to respond to outbreak infections, and which can call on the support and resources of a central centre of excellence. CONCLUSIONS: It is crucial that the field of epidemic science matures to place patients at the heart of the response. This can only be achieved when patient-centred research is integrated in the outbreak response from day one and practical steps are taken to reduce the barriers to the generation of reliable and useful evidence.",2016 Dec 19,"['Rojek, Amanda M.', 'Horby, Peter W.']",BMC Med,,,True
31ce4647dd3ce32716212b10cfa8b05724dc32fd,PMC,The Identification and Characterization of Two Novel Epitopes on the Nucleocapsid Protein of the Porcine Epidemic Diarrhea Virus,http://dx.doi.org/10.1038/srep39010,PMC5171872,27991537,CC BY,"Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe diarrhea and death, particularly in neonatal piglets. The nucleocapsid protein (N protein) of PEDV presents strong immunogenicity and contributes to the cross-reactivity between PEDV and TGEV. However, the characterization of epitopes on the PEDV N protein remains largely unknown. Here, two monoclonal antibodies (MAbs) specific to the N protein of a PEDV strain, FJzz1/2011, were generated and screened against a partially overlapping library of 24 GST-fusion N protein-truncated constructs. We confirmed that residues 18–133 (designated NEP-D4) and residues 252–262 (designated NEP-D6) were the epitopes targeted by MAbs PN-D4 and PN-D6, respectively. Sequence analysis revealed that these two epitopes were highly conserved among PEDV strains but were significantly different from other members of the Coronavirinae subfamily. Western blot analysis showed that they could be specifically recognized by PEDV antisera but could not be recognized by TGEV hyperimmune antisera. Indirect immunofluorescence (IFA) assays confirmed no cross-reaction between these two MAbs and TGEV. In addition, the freeze-thaw cycle and protease treatment results indicated that NEP-D4 was intrinsically disordered. All these results suggest that these two novel epitopes and their cognate MAbs could serve as the basis for the development of precise diagnostic assays for PEDV.",2016 Dec 19,"['Wang, Kang', 'Xie, Chun', 'Zhang, Jianan', 'Zhang, Wenchao', 'Yang, Deqiang', 'Yu, Lingxue', 'Jiang, Yifeng', 'Yang, Shen', 'Gao, Fei', 'Yang, Zhibiao', 'Zhou, Yanjun', 'Tong, Guangzhi']",Sci Rep,,,True
a3f75f7f759c60426c7a47b9cd2470a70ef244c0,PMC,Nonstructural Protein 11 of Porcine Reproductive and Respiratory Syndrome Virus Suppresses Both MAVS and RIG-I Expression as One of the Mechanisms to Antagonize Type I Interferon Production,http://dx.doi.org/10.1371/journal.pone.0168314,PMC5172586,27997564,CC BY,"Type I interferons (IFN-α/β) play a key role in antiviral defense, and porcine reproductive and respiratory syndrome virus (PRRSV) is known to down-regulate the IFN response in virus-infected cells and pigs. In this study, we showed that the overexpression of nsp11 of PRRSV induced a strong suppression of IFN production. Nsp11 suppressed both IRF3 and NF-κB activities when stimulated with a dsRNA analogue and TNF-α, respectively. This suppression was RLR dependent, since the transcripts and proteins of MAVS and RIG-I, two critical factors in RLR-mediated pathway, were both found to be reduced in the presence of overexpressed nsp11. Since nsp11 is an endoribonuclease (EndoU), the structure function relationship was examined using a series of nsp11 EndoU mutant plasmids. The mutants that impaired the EndoU activity failed to suppress IFN and led to the normal expression of MAVS. Seven single amino acid substitutions (4 in subdomain A and 3 in subdomain B) plus one insertion (frame-shift in nsp11) were then introduced into PRRSV infectious cDNA clones to generate nsp11 mutant viruses. Unfortunately, all EndoU knock-out nsp11 mutant viruses appeared replication-defective and no progenies were produced. Three mutations in EndoU subdomain A expressed the N and nsp2/3 proteins but their infectivity diminished after 2 passages. Taken together, our data show that PRRSV nsp11 endoribonuclease activity is critical for both viral replication and IFN antagonism. More importantly, the endoribonuclease activity of nsp11 demonstrates the substrate specificity towards MAVS and RIG-I (transcripts and proteins) over p65 and IRF3 in the context of gene transfection and overexpression. This is likely a mechanism of nsp11 suppression of type I IFN production.",2016 Dec 20,"['Sun, Yan', 'Ke, Hanzhong', 'Han, Mingyuan', 'Chen, Ning', 'Fang, Weihuan', 'Yoo, Dongwan']",PLoS One,,,True
26bdc177821e0161d138236656dafefe2f9f6900,PMC,Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection,http://dx.doi.org/10.1186/1471-2121-5-32,PMC517494,15333144,CC BY,"BACKGROUND: Viruses are obligate intracellular parasites and rely upon the host cell for different steps in their life cycles. The characterization of cellular genes required for virus infection and/or cell killing will be essential for understanding viral life cycles, and may provide cellular targets for new antiviral therapies. RESULTS: A gene entrapment approach was used to identify candidate cellular genes that affect reovirus infection or virus induced cell lysis. Four of the 111 genes disrupted in clones selected for resistance to infection by reovirus type 1 involved the insulin growth factor-2 (IGF-II) pathway, including: the mannose-6-phosphate/IGF2 receptor (Igf2r), a protease associated with insulin growth factor binding protein 5 (Prss11), and the CTCF transcriptional regulator (Ctcf). The disruption of Ctcf, which encodes a repressor of Igf2, was associated with enhanced Igf2 gene expression. Plasmids expressing either the IGF-II pro-hormone or IGF-II without the carboxy terminal extension (E)-peptide sequence independently conferred high levels of cellular resistance to reovirus infection. Forced IGF-II expression results in a block in virus disassembly. In addition, Ctcf disruption and forced Igf2 expression both enabled cells to proliferate in soft agar, a phenotype associated with malignant growth in vivo. CONCLUSION: These results indicate that IGF-II, and by inference other components of the IGF-II signalling pathway, can confer resistance to lytic reovirus infection. This report represents the first use of gene entrapment to identify host factors affecting virus infection. Concomitant transformation observed in some virus resistant cells illustrates a potential mechanism of carcinogenesis associated with chronic virus infection.",2004 Aug 27,"['Sheng, Jinsong', 'Organ, Edward L', 'Hao, Chuanming', 'Wells, K Sam', 'Ruley, H Earl', 'Rubin, Donald H']",BMC Cell Biol,,,True
626e2623bbb406b7fc1bd5b1da3ff4eb30e3888c,PMC,Mechanical unfolding kinetics of the SRV-1 gag-pro mRNA pseudoknot: possible implications for −1 ribosomal frameshifting stimulation,http://dx.doi.org/10.1038/srep39549,PMC5175198,28000744,CC BY,"Minus-one ribosomal frameshifting is a translational recoding mechanism widely utilized by many RNA viruses to generate accurate ratios of structural and catalytic proteins. An RNA pseudoknot structure located in the overlapping region of the gag and pro genes of Simian Retrovirus type 1 (SRV-1) stimulates frameshifting. However, the experimental characterization of SRV-1 pseudoknot (un)folding dynamics and the effect of the base triple formation is lacking. Here, we report the results of our single-molecule nanomanipulation using optical tweezers and theoretical simulation by steered molecular dynamics. Our results directly reveal that the energetic coupling between loop 2 and stem 1 via minor-groove base triple formation enhances the mechanical stability. The terminal base pair in stem 1 (directly in contact with a translating ribosome at the slippery site) also affects the mechanical stability of the pseudoknot. The −1 frameshifting efficiency is positively correlated with the cooperative one-step unfolding force and inversely correlated with the one-step mechanical unfolding rate at zero force. A significantly improved correlation was observed between −1 frameshifting efficiency and unfolding rate at forces of 15–35 pN, consistent with the fact that the ribosome is a force-generating molecular motor with helicase activity. No correlation was observed between thermal stability and −1 frameshifting efficiency.",2016 Dec 21,"['Zhong, Zhensheng', 'Yang, Lixia', 'Zhang, Haiping', 'Shi, Jiahao', 'Vandana, J. Jeya', 'Lam, Do Thuy Uyen Ha', 'Olsthoorn, René C. L.', 'Lu, Lanyuan', 'Chen, Gang']",Sci Rep,,,True
cd97d6b4e0495ffd6543a25ac01e843b8efa6b6c,PMC,Mechanical unfolding kinetics of the SRV-1 gag-pro mRNA pseudoknot: possible implications for −1 ribosomal frameshifting stimulation,http://dx.doi.org/10.1038/srep39549,PMC5175198,28000744,CC BY,"Minus-one ribosomal frameshifting is a translational recoding mechanism widely utilized by many RNA viruses to generate accurate ratios of structural and catalytic proteins. An RNA pseudoknot structure located in the overlapping region of the gag and pro genes of Simian Retrovirus type 1 (SRV-1) stimulates frameshifting. However, the experimental characterization of SRV-1 pseudoknot (un)folding dynamics and the effect of the base triple formation is lacking. Here, we report the results of our single-molecule nanomanipulation using optical tweezers and theoretical simulation by steered molecular dynamics. Our results directly reveal that the energetic coupling between loop 2 and stem 1 via minor-groove base triple formation enhances the mechanical stability. The terminal base pair in stem 1 (directly in contact with a translating ribosome at the slippery site) also affects the mechanical stability of the pseudoknot. The −1 frameshifting efficiency is positively correlated with the cooperative one-step unfolding force and inversely correlated with the one-step mechanical unfolding rate at zero force. A significantly improved correlation was observed between −1 frameshifting efficiency and unfolding rate at forces of 15–35 pN, consistent with the fact that the ribosome is a force-generating molecular motor with helicase activity. No correlation was observed between thermal stability and −1 frameshifting efficiency.",2016 Dec 21,"['Zhong, Zhensheng', 'Yang, Lixia', 'Zhang, Haiping', 'Shi, Jiahao', 'Vandana, J. Jeya', 'Lam, Do Thuy Uyen Ha', 'Olsthoorn, René C. L.', 'Lu, Lanyuan', 'Chen, Gang']",Sci Rep,,,True
def1cf77e1ef84f4373a342e23145be05ec5e226,PMC,Mutational dynamics of the SARS coronavirus in cell culture and human populations isolated in 2003,http://dx.doi.org/10.1186/1471-2334-4-32,PMC517714,15347429,CC BY,"BACKGROUND: The SARS coronavirus is the etiologic agent for the epidemic of the Severe Acute Respiratory Syndrome. The recent emergence of this new pathogen, the careful tracing of its transmission patterns, and the ability to propagate in culture allows the exploration of the mutational dynamics of the SARS-CoV in human populations. METHODS: We sequenced complete SARS-CoV genomes taken from primary human tissues (SIN3408, SIN3725V, SIN3765V), cultured isolates (SIN848, SIN846, SIN842, SIN845, SIN847, SIN849, SIN850, SIN852, SIN3408L), and five consecutive Vero cell passages (SIN2774_P1, SIN2774_P2, SIN2774_P3, SIN2774_P4, SIN2774_P5) arising from SIN2774 isolate. These represented individual patient samples, serial in vitro passages in cell culture, and paired human and cell culture isolates. Employing a refined mutation filtering scheme and constant mutation rate model, the mutation rates were estimated and the possible date of emergence was calculated. Phylogenetic analysis was used to uncover molecular relationships between the isolates. RESULTS: Close examination of whole genome sequence of 54 SARS-CoV isolates identified before 14(th )October 2003, including 22 from patients in Singapore, revealed the mutations engendered during human-to-Vero and Vero-to-human transmission as well as in multiple Vero cell passages in order to refine our analysis of human-to-human transmission. Though co-infection by different quasipecies in individual tissue samples is observed, the in vitro mutation rate of the SARS-CoV in Vero cell passage is negligible. The in vivo mutation rate, however, is consistent with estimates of other RNA viruses at approximately 5.7 × 10(-6 )nucleotide substitutions per site per day (0.17 mutations per genome per day), or two mutations per human passage (adjusted R-square = 0.4014). Using the immediate Hotel M contact isolates as roots, we observed that the SARS epidemic has generated four major genetic groups that are geographically associated: two Singapore isolates, one Taiwan isolate, and one North China isolate which appears most closely related to the putative SARS-CoV isolated from a palm civet. Non-synonymous mutations are centered in non-essential ORFs especially in structural and antigenic genes such as the S and M proteins, but these mutations did not distinguish the geographical groupings. However, no non-synonymous mutations were found in the 3CLpro and the polymerase genes. CONCLUSIONS: Our results show that the SARS-CoV is well adapted to growth in culture and did not appear to undergo specific selection in human populations. We further assessed that the putative origin of the SARS epidemic was in late October 2002 which is consistent with a recent estimate using cases from China. The greater sequence divergence in the structural and antigenic proteins and consistent deletions in the 3' – most portion of the viral genome suggest that certain selection pressures are interacting with the functional nature of these validated and putative ORFs.",2004 Sep 6,"['Vega, Vinsensius B', 'Ruan, Yijun', 'Liu, Jianjun', 'Lee, Wah Heng', 'Wei, Chia Lin', 'Se-Thoe, Su Yun', 'Tang, Kin Fai', 'Zhang, Tao', 'Kolatkar, Prasanna R', 'Ooi, Eng Eong', 'Ling, Ai Ee', 'Stanton, Lawrence W', 'Long, Philip M', 'Liu, Edison T']",BMC Infect Dis,,,True
cd1d0cb4b82d5479e2aa72ec3d3cde6aae4a4eaf,PMC,Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay,http://dx.doi.org/10.1128/mSphere.00334-16,PMC5177731,28028546,CC BY,"Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.",2016 Dec 21,"['Rigatti, Lora H.', 'Toptan, Tuna', 'Newsome, Joseph T.', 'Moore, Patrick S.', 'Chang, Yuan']",mSphere,,,True
c1463986f2df7695fca3d8e5ef31faea5751b062,PMC,Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay,http://dx.doi.org/10.1128/mSphere.00334-16,PMC5177731,28028546,CC BY,"Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.",2016 Dec 21,"['Rigatti, Lora H.', 'Toptan, Tuna', 'Newsome, Joseph T.', 'Moore, Patrick S.', 'Chang, Yuan']",mSphere,,,False
02fe25fbb0d56b029e8430d15c6477cc8a60cfbf,PMC,Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay,http://dx.doi.org/10.1128/mSphere.00334-16,PMC5177731,28028546,CC BY,"Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.",2016 Dec 21,"['Rigatti, Lora H.', 'Toptan, Tuna', 'Newsome, Joseph T.', 'Moore, Patrick S.', 'Chang, Yuan']",mSphere,,,False
f12c46cf0ce9bbb550db15686c35cbaf93675f9b,PMC,Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay,http://dx.doi.org/10.1128/mSphere.00334-16,PMC5177731,28028546,CC BY,"Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.",2016 Dec 21,"['Rigatti, Lora H.', 'Toptan, Tuna', 'Newsome, Joseph T.', 'Moore, Patrick S.', 'Chang, Yuan']",mSphere,,,False
41de90ca9d6f6a18e6f89d479e3fd8160997a14d,PMC,Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay,http://dx.doi.org/10.1128/mSphere.00334-16,PMC5177731,28028546,CC BY,"Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.",2016 Dec 21,"['Rigatti, Lora H.', 'Toptan, Tuna', 'Newsome, Joseph T.', 'Moore, Patrick S.', 'Chang, Yuan']",mSphere,,,False
107ccec688fb89790d2e34288f7eeba5ef7711aa,PMC,Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay,http://dx.doi.org/10.1128/mSphere.00334-16,PMC5177731,28028546,CC BY,"Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.",2016 Dec 21,"['Rigatti, Lora H.', 'Toptan, Tuna', 'Newsome, Joseph T.', 'Moore, Patrick S.', 'Chang, Yuan']",mSphere,,,False
6d5428a39bf922573570819e724cd7db07fb79f9,PMC,Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay,http://dx.doi.org/10.1128/mSphere.00334-16,PMC5177731,28028546,CC BY,"Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.",2016 Dec 21,"['Rigatti, Lora H.', 'Toptan, Tuna', 'Newsome, Joseph T.', 'Moore, Patrick S.', 'Chang, Yuan']",mSphere,,,False
c52372f0295a7cd5d07b677dee5360d634d6a394,PMC,The interdependent complexity of disaster and Middle East Respiratory Syndrome,http://dx.doi.org/10.4178/epih.e2016053,PMC5177800,27899024,CC BY,,2016 Nov 28,"Lee, Wonjae",Epidemiol Health,,,False
cf88f594fcb494d7147df36623227c897c385645,PMC,The interdependent complexity of disaster and Middle East Respiratory Syndrome,http://dx.doi.org/10.4178/epih.e2016053,PMC5177800,27899024,CC BY,,2016 Nov 28,"Lee, Wonjae",Epidemiol Health,,,False
abfbd54f647f1110848e0d711303e92b55f15ab2,PMC,Psychological trauma of Middle East Respiratory Syndrome victims and bereaved families,http://dx.doi.org/10.4178/epih.e2016054,PMC5177804,27919121,CC BY,,2016 Dec 2,"Sim, Minyoung",Epidemiol Health,,,False
f906ff51f4ba98a52133c1cfea59ee9420e3b0fc,PMC,Psychological trauma of Middle East Respiratory Syndrome victims and bereaved families,http://dx.doi.org/10.4178/epih.e2016054,PMC5177804,27919121,CC BY,,2016 Dec 2,"Sim, Minyoung",Epidemiol Health,,,False
344057fa7bef9619bf39e1d681ab054048949e75,PMC,Mental health status of people isolated due to Middle East Respiratory Syndrome,http://dx.doi.org/10.4178/epih.e2016048,PMC5177805,28196409,CC BY,"OBJECTIVES: Isolation due to the management of infectious diseases is thought to affect mental health, but the effects are still unknown. We examined the prevalence of anxiety symptoms and anger in persons isolated during the Middle East Respiratory Syndrome (MERS) epidemic both at isolation period and at four to six months after release from isolation. We also determined risk factors associated with these symptoms at four to six months. METHODS: Of 14,992 individuals isolated for 2-week due to having contact with MERS patients in 2015, when MERS was introduced to Korea, 1,692 individuals were included in this study. Anxiety symptoms were evaluated with the Generalized Anxiety Disorder 7-item scale and anger was assessed with the State-Trait Anger Expression Inventory at four to six months after release from isolation for MERS. RESULTS: Of 1,692 who came in contact with MERS patients, 1,656 were not diagnosed with MERS. Among 1,656, anxiety symptoms showed 7.6% (95% confidence interval [CI], 6.3 to 8.9%) and feelings of anger were present in 16.6% (95% CI, 14.8 to 18.4%) during the isolation period. At four to six months after release from isolation, anxiety symptoms were observed in 3.0% (95%CI, 2.2 to 3.9%). Feelings of anger were present in 6.4% (95% CI, 5.2 to 7.6%). Risk factors for experiencing anxiety symptoms and anger at four to six months after release included symptoms related to MERS during isolation, inadequate supplies (food, clothes, accommodation), social networking activities (email, text, Internet), history of psychiatric illnesses, and financial loss. CONCLUSIONS: Mental health problems at four to six month after release from isolation might be prevented by providing mental health support to individuals with vulnerable mental health, and providing accurate information as well as appropriate supplies, including food, clothes, and accommodation.",2016 Nov 5,"['Jeong, Hyunsuk', 'Yim, Hyeon Woo', 'Song, Yeong-Jun', 'Ki, Moran', 'Min, Jung-Ah', 'Cho, Juhee', 'Chae, Jeong-Ho']",Epidemiol Health,,,True
be0098a38881944590f4d51d6e29bf4e616267e9,PMC,Mental health status of people isolated due to Middle East Respiratory Syndrome,http://dx.doi.org/10.4178/epih.e2016048,PMC5177805,28196409,CC BY,"OBJECTIVES: Isolation due to the management of infectious diseases is thought to affect mental health, but the effects are still unknown. We examined the prevalence of anxiety symptoms and anger in persons isolated during the Middle East Respiratory Syndrome (MERS) epidemic both at isolation period and at four to six months after release from isolation. We also determined risk factors associated with these symptoms at four to six months. METHODS: Of 14,992 individuals isolated for 2-week due to having contact with MERS patients in 2015, when MERS was introduced to Korea, 1,692 individuals were included in this study. Anxiety symptoms were evaluated with the Generalized Anxiety Disorder 7-item scale and anger was assessed with the State-Trait Anger Expression Inventory at four to six months after release from isolation for MERS. RESULTS: Of 1,692 who came in contact with MERS patients, 1,656 were not diagnosed with MERS. Among 1,656, anxiety symptoms showed 7.6% (95% confidence interval [CI], 6.3 to 8.9%) and feelings of anger were present in 16.6% (95% CI, 14.8 to 18.4%) during the isolation period. At four to six months after release from isolation, anxiety symptoms were observed in 3.0% (95%CI, 2.2 to 3.9%). Feelings of anger were present in 6.4% (95% CI, 5.2 to 7.6%). Risk factors for experiencing anxiety symptoms and anger at four to six months after release included symptoms related to MERS during isolation, inadequate supplies (food, clothes, accommodation), social networking activities (email, text, Internet), history of psychiatric illnesses, and financial loss. CONCLUSIONS: Mental health problems at four to six month after release from isolation might be prevented by providing mental health support to individuals with vulnerable mental health, and providing accurate information as well as appropriate supplies, including food, clothes, and accommodation.",2016 Nov 5,"['Jeong, Hyunsuk', 'Yim, Hyeon Woo', 'Song, Yeong-Jun', 'Ki, Moran', 'Min, Jung-Ah', 'Cho, Juhee', 'Chae, Jeong-Ho']",Epidemiol Health,,,True
d49cee8c7a1dcbaf01f8b3126ba8bc7b9ead7a5a,PMC,Effective risk governance requires risk communication experts,http://dx.doi.org/10.4178/epih.e2016055,PMC5177806,27919122,CC BY,,2016 Dec 2,"Paek, Hye-Jin",Epidemiol Health,,,True
6f207ad75048739d35ad460224c267150c18ad54,PMC,Effective risk governance requires risk communication experts,http://dx.doi.org/10.4178/epih.e2016055,PMC5177806,27919122,CC BY,,2016 Dec 2,"Paek, Hye-Jin",Epidemiol Health,,,False
77ced9eec3817dd81f3b38b19086ba07b271208f,PMC,Cross-protective efficacy of dendritic cells targeting conserved influenza virus antigen expressed by Lactobacillus plantarum,http://dx.doi.org/10.1038/srep39665,PMC5177883,28004787,CC BY,"Avian influenza virus (AIV) can infect birds and mammals, including humans, and are thus a serious threat to public health. Vaccination is vital for controlling AIV circulation. In this study, we generated a recombinant lactobacillus expressing the NP-M1-DCpep of H9N2 avian influenza virus and evaluated the activation effect of NC8-pSIP409-NP-M1-DCpep on dendritic cells (DCs) in a mouse model. The specific mucosal antibody responses and B and T cell responses in lymphoid tissues were also characterized. Importantly, we confirmed that specific CD8 T cells presented in vitro and antigen-specific cytotoxicity (activated the expression of CD107a) and in vivo antigen-specific cytotoxicity after vaccination. The adoptive transfer of NC8-pSIP409-NP-M1-DCpep-primed CD8(+) T cells into NOD-SCID mice resulted in effective protection against mouse-adapted AIV infection. In addition, we observed protection in immunized mice challenged with mouse-adapted H9N2 AIV and H1N1 influenza virus, as evidenced by reductions in the lung virus titers, improvements in lung pathology, and weight loss and complete survival. Our data are promising for the generation of effective, non-traditional influenza vaccines against AIVs.",2016 Dec 22,"['Yang, Wen-Tao', 'Shi, Shao-Hua', 'Yang, Gui-Lian', 'Jiang, Yan-Long', 'Zhao, Liang', 'Li, Yu', 'Wang, Chun-Feng']",Sci Rep,,,True
4fcf6dedbf15427b8516654a5a24fbce54fb4b2a,PMC,Cross-protective efficacy of dendritic cells targeting conserved influenza virus antigen expressed by Lactobacillus plantarum,http://dx.doi.org/10.1038/srep39665,PMC5177883,28004787,CC BY,"Avian influenza virus (AIV) can infect birds and mammals, including humans, and are thus a serious threat to public health. Vaccination is vital for controlling AIV circulation. In this study, we generated a recombinant lactobacillus expressing the NP-M1-DCpep of H9N2 avian influenza virus and evaluated the activation effect of NC8-pSIP409-NP-M1-DCpep on dendritic cells (DCs) in a mouse model. The specific mucosal antibody responses and B and T cell responses in lymphoid tissues were also characterized. Importantly, we confirmed that specific CD8 T cells presented in vitro and antigen-specific cytotoxicity (activated the expression of CD107a) and in vivo antigen-specific cytotoxicity after vaccination. The adoptive transfer of NC8-pSIP409-NP-M1-DCpep-primed CD8(+) T cells into NOD-SCID mice resulted in effective protection against mouse-adapted AIV infection. In addition, we observed protection in immunized mice challenged with mouse-adapted H9N2 AIV and H1N1 influenza virus, as evidenced by reductions in the lung virus titers, improvements in lung pathology, and weight loss and complete survival. Our data are promising for the generation of effective, non-traditional influenza vaccines against AIVs.",2016 Dec 22,"['Yang, Wen-Tao', 'Shi, Shao-Hua', 'Yang, Gui-Lian', 'Jiang, Yan-Long', 'Zhao, Liang', 'Li, Yu', 'Wang, Chun-Feng']",Sci Rep,,,True
03a158fb5fcbfccd841b4a9638e840a0302b9459,PMC,The DE and FG loops of the HPV major capsid protein contribute to the epitopes of vaccine-induced cross-neutralising antibodies,http://dx.doi.org/10.1038/srep39730,PMC5177933,28004837,CC BY,"The human papillomavirus (HPV) vaccines consist of major capsid protein (L1) virus-like particles (VLP) and are highly efficacious against the development of cervical cancer precursors attributable to oncogenic genotypes, HPV16 and HPV18. A degree of vaccine-induced cross-protection has also been demonstrated against genetically-related genotypes in the Alpha-7 (HPV18-like) and Alpha-9 (HPV16-like) species groups which is coincident with the detection of L1 cross-neutralising antibodies. In this study the L1 domains recognised by inter-genotype cross-neutralising antibodies were delineated. L1 crystallographic homology models predicted a degree of structural diversity between the L1 loops of HPV16 and the non-vaccine Alpha-9 genotypes. These structural predictions informed the design of chimeric pseudovirions with inter-genotype loop swaps which demonstrated that the L1 domains recognised by inter-genotype cross-neutralising antibodies comprise residues within the DE loop and the late region of the FG loop. These data contribute to our understanding of the L1 domains recognised by vaccine-induced cross-neutralising antibodies. Such specificities may play a critical role in vaccine-induced cross-protection.",2016 Dec 22,"['Bissett, Sara L.', 'Godi, Anna', 'Beddows, Simon']",Sci Rep,,,True
02843e9be924677d6541e0221a26501ce2111aaa,PMC,The differentiated airway epithelium infected by influenza viruses maintains the barrier function despite a dramatic loss of ciliated cells,http://dx.doi.org/10.1038/srep39668,PMC5177954,28004801,CC BY,"Virus-host interactions in the respiratory epithelium during long term influenza virus infection are not well characterized. Therefore, we developed an air-liquid interface culture system for differentiated porcine respiratory epithelial cells to study the effect of virus-induced cellular damage. In our well-differentiated cells, α2,6-linked sialic acid is predominantly expressed on the apical surface and the basal cells mainly express α2,3-linked sialic acid. During the whole infection period, release of infectious virus was maintained at a high titre for more than seven days. The infected epithelial cells were subject to apoptosis resulting in the loss of ciliated cells together with a thinner thickness. Nevertheless, the airway epithelium maintained trans-epithelial electrical resistance and retained its barrier function. The loss of ciliated cells was compensated by the cells which contained the KRT5 basal cell marker but were not yet differentiated into ciliated cells. These specialized cells showed an increase of α2,3-linked sialic acid on the apical surface. In sum, our results help to explain the localized infection of the airway epithelium by influenza viruses. The impairment of mucociliary clearance in the epithelial cells provides an explanation why prior viral infection renders the host more susceptible to secondary co-infection by another pathogen.",2016 Dec 22,"['Wu, Nai-Huei', 'Yang, Wei', 'Beineke, Andreas', 'Dijkman, Ronald', 'Matrosovich, Mikhail', 'Baumgärtner, Wolfgang', 'Thiel, Volker', 'Valentin-Weigand, Peter', 'Meng, Fandan', 'Herrler, Georg']",Sci Rep,,,True
31cfa31a4d8a26ca083257be0e6dce51562d8c6d,PMC,Respiratory Antiviral Immunity and Immunobiotics: Beneficial Effects on Inflammation-Coagulation Interaction during Influenza Virus Infection,http://dx.doi.org/10.3389/fimmu.2016.00633,PMC5179578,28066442,CC BY,"Influenza virus (IFV) is a major respiratory pathogen of global importance, and the cause of a high degree of morbidity and mortality, especially in high-risk populations such as infants, elderly, and immunocompromised hosts. Given its high capacity to change antigenically, acquired immunity is often not effective to limit IFV infection and therefore vaccination must be constantly redesigned to achieve effective protection. Improvement of respiratory and systemic innate immune mechanisms has been proposed to reduce the incidence and severity of IFV disease. In the last decade, several research works have demonstrated that microbes with the capacity to modulate the mucosal immune system (immunobiotics) are a potential alternative to beneficially modulate the outcome of IFV infection. This review provides an update of the current status on the modulation of respiratory immunity by orally and nasally administered immunobiotics, and their beneficial impact on IFV clearance and inflammatory-mediated lung tissue damage. In particular, we describe the research of our group that investigated the influence of immunobiotics on inflammation–coagulation interactions during IFV infection. Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract.",2016 Dec 23,"['Zelaya, Hortensia', 'Alvarez, Susana', 'Kitazawa, Haruki', 'Villena, Julio']",Front Immunol,,,True
37d6ce7eabf4b6177b9462771494c7c2fc36e5ee,PMC,Integrated biological–behavioural surveillance in pandemic-threat warning systems,http://dx.doi.org/10.2471/BLT.16.175984,PMC5180348,28053365,CC BY,"Economically and politically disruptive disease outbreaks are a hallmark of the 21st century. Although pandemics are driven by human behaviours, current surveillance systems for identifying pandemic threats are largely reliant on the monitoring of disease outcomes in clinical settings. Standardized integrated biological–behavioural surveillance could, and should, be used in community settings to complement such clinical monitoring. The usefulness of such an approach has already been demonstrated in studies on human immunodeficiency virus, where integrated surveillance contributed to a biologically based and quantifiable understanding of the behavioural risk factors associated with the transmission dynamics of the virus. When designed according to Strengthening the Reporting of Observational Studies in Epidemiology criteria, integrated surveillance requires that both behavioural risk factors – i.e. exposure variables – and disease-indicator outcome variables be measured in behavioural surveys. In the field of pandemic threats, biological outcome data could address the weaknesses of self-reported data collected in behavioural surveys. Data from serosurveys of viruses with pandemic potential, collected under non-outbreak conditions, indicate that serosurveillance could be used to predict future outbreaks. When conducted together, behavioural surveys and serosurveys could warn of future pandemics, potentially before the disease appears in clinical settings. Traditional disease-outcome surveillance must be frequent and ongoing to remain useful but behavioural surveillance remains informative even if conducted much less often, since behaviour change occurs slowly over time. Only through knowledge of specific behavioural risk factors can interventions and policies that can prevent the next pandemic be developed.",2017 Jan 1,"['Miller, Maureen', 'Hagan, Emily']",Bull World Health Organ,,,True
90b065409490de2813ab71b65ca8b401ec55b356,PMC,Avian H11 influenza virus isolated from domestic poultry in a Colombian live animal market,http://dx.doi.org/10.1038/emi.2016.121,PMC5180366,27924808,CC BY,"Live animal markets (LAMs) are an essential source of food and trade in Latin American countries; however, they can also serve as ‘hotbeds' for the emergence and potential spillover of avian influenza viruses (AIV). Despite extensive knowledge of AIV in Asian LAMs, little is known about the prevalence South American LAMs. To fill this gap in knowledge, active surveillance was carried out at the major LAM in Medellin, Colombia between February and September 2015. During this period, overall prevalence in the market was 2.67% and a North American origin H11N2 AIV most similar to a virus isolated from Chilean shorebirds asymptomatically spread through multiple bird species in the market resulting in 17.0% positivity at peak of infection. Phenotypically, the H11 viruses displayed no known molecular markers associated with increased virulence in birds or mammals, had α2,3-sialic acid binding preference, and caused minimal replication in vitro and little morbidity in vivo. However, the Colombian H11N2 virus replicated and transmitted effectively in chickens explaining the spread throughout the market. Genetic similarity to H11 viruses isolated from North and South American shorebirds suggest that the LAM occurrence may have resulted from a wild bird to domestic poultry spillover event. The ability to spread in domestic poultry as well as potential for human infection by H11 viruses highlight the need for enhanced AIV surveillance in South America in both avian species and humans.",2016 Dec 7,"['Jiménez-Bluhm, Pedro', 'Karlsson, Erik A', 'Ciuoderis, Karl A', 'Cortez, Valerie', 'Marvin, Shauna A', 'Hamilton-West, Christopher', 'Schultz-Cherry, Stacey', 'Osorio, Jorge E']",Emerg Microbes Infect,,,True
18176d1030fff6410b83e0df1591b3617fc739cb,PMC,A camel-derived MERS-CoV with a variant spike protein cleavage site and distinct fusion activation properties,http://dx.doi.org/10.1038/emi.2016.125,PMC5180369,27999426,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) continues to circulate in both humans and camels, and the origin and evolution of the virus remain unclear. Here we characterize the spike protein of a camel-derived MERS-CoV (NRCE-HKU205) identified in 2013, early in the MERS outbreak. NRCE-HKU205 spike protein has a variant cleavage motif with regard to the S2′ fusion activation site—notably, a novel substitution of isoleucine for the otherwise invariant serine at the critical P1′ cleavage site position. The substitutions resulted in a loss of furin-mediated cleavage, as shown by fluorogenic peptide cleavage and western blot assays. Cell–cell fusion and pseudotyped virus infectivity assays demonstrated that the S2′ substitutions decreased spike-mediated fusion and viral entry. However, cathepsin and trypsin-like protease activation were retained, albeit with much reduced efficiency compared with the prototypical EMC/2012 human strain. We show that NRCE-HKU205 has more limited fusion activation properties possibly resulting in more restricted viral tropism and may represent an intermediate in the complex pattern of MERS-CoV ecology and evolution.",2016 Dec 21,"['Millet, Jean Kaoru', 'Goldstein, Monty E', 'Labitt, Rachael N', 'Hsu, Hung-Lun', 'Daniel, Susan', 'Whittaker, Gary R']",Emerg Microbes Infect,,,True
3fcc0c9ff97448fd834d65f22598be89ee20c4a0,PMC,A camel-derived MERS-CoV with a variant spike protein cleavage site and distinct fusion activation properties,http://dx.doi.org/10.1038/emi.2016.125,PMC5180369,27999426,CC BY,"Middle East respiratory syndrome coronavirus (MERS-CoV) continues to circulate in both humans and camels, and the origin and evolution of the virus remain unclear. Here we characterize the spike protein of a camel-derived MERS-CoV (NRCE-HKU205) identified in 2013, early in the MERS outbreak. NRCE-HKU205 spike protein has a variant cleavage motif with regard to the S2′ fusion activation site—notably, a novel substitution of isoleucine for the otherwise invariant serine at the critical P1′ cleavage site position. The substitutions resulted in a loss of furin-mediated cleavage, as shown by fluorogenic peptide cleavage and western blot assays. Cell–cell fusion and pseudotyped virus infectivity assays demonstrated that the S2′ substitutions decreased spike-mediated fusion and viral entry. However, cathepsin and trypsin-like protease activation were retained, albeit with much reduced efficiency compared with the prototypical EMC/2012 human strain. We show that NRCE-HKU205 has more limited fusion activation properties possibly resulting in more restricted viral tropism and may represent an intermediate in the complex pattern of MERS-CoV ecology and evolution.",2016 Dec 21,"['Millet, Jean Kaoru', 'Goldstein, Monty E', 'Labitt, Rachael N', 'Hsu, Hung-Lun', 'Daniel, Susan', 'Whittaker, Gary R']",Emerg Microbes Infect,,,False
f8de6043ca1a372d6ea60880034cfb6abbc4b147,PMC,Polyphyletic origin of MERS coronaviruses and isolation of a novel clade A strain from dromedary camels in the United Arab Emirates,http://dx.doi.org/10.1038/emi.2016.129,PMC5180373,27999424,CC BY,"Little is known regarding the molecular epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) circulating in dromedaries outside Saudi Arabia. To address this knowledge gap, we sequenced 10 complete genomes of MERS-CoVs isolated from 2 live and 8 dead dromedaries from different regions in the United Arab Emirates (UAE). Phylogenetic analysis revealed one novel clade A strain, the first detected in the UAE, and nine clade B strains. Strain D998/15 had a distinct phylogenetic position within clade A, being more closely related to the dromedary isolate NRCE-HKU205 from Egypt than to the human isolates EMC/2012 and Jordan-N3/2012. A comparison of predicted protein sequences also demonstrated the existence of two clade A lineages with unique amino acid substitutions, A1 (EMC/2012 and Jordan-N3/2012) and A2 (D998/15 and NRCE-HKU205), circulating in humans and camels, respectively. The nine clade B isolates belong to three distinct lineages: B1, B3 and B5. Two B3 strains, D1271/15 and D1189.1/15, showed evidence of recombination between lineages B4 and B5 in ORF1ab. Molecular clock analysis dated the time of the most recent common ancestor (tMRCA) of clade A to March 2011 and that of clade B to November 2011. Our data support a polyphyletic origin of MERS-CoV in dromedaries and the co-circulation of diverse MERS-CoVs including recombinant strains in the UAE.",2016 Dec 21,"['Lau, Susanna K P', 'Wernery, Renate', 'Wong, Emily Y M', 'Joseph, Sunitha', 'Tsang, Alan K L', 'Patteril, Nissy Annie Georgy', 'Elizabeth, Shyna K', 'Chan, Kwok-Hung', 'Muhammed, Rubeena', 'Kinne, Jöerg', 'Yuen, Kwok-Yung', 'Wernery, Ulrich', 'Woo, Patrick C Y']",Emerg Microbes Infect,,,True
cd3eeb911617dd22ee6f0d1843e19ba1d255e133,PMC,Loop-Mediated Isothermal Amplification (LAMP): Emergence As an Alternative Technology for Herbal Medicine Identification,http://dx.doi.org/10.3389/fpls.2016.01956,PMC5183589,28082999,CC BY,"Correct identification of medicinal plant ingredients is essential for their safe use and for the regulation of herbal drug supply chain. Loop-mediated isothermal amplification (LAMP) is a recently developed approach to identify herbal medicine species. This novel molecular biology technique enables timely and accurate testing, especially in settings where infrastructures to support polymerase chain reaction facilities are lacking. Studies that used this method have altered our view on the extent and complexity of herbal medicine identification. In this review, we give an introduction into LAMP analysis, covers the basic principles and important aspects in the development of LAMP analysis method. Then we presented a critical review of the application of LAMP-based methods in detecting and identifying raw medicinal plant materials and their processed products. We also provide a practical standard operating procedure (SOP) for the utilization of the LAMP protocol in herbal authentication, and consider the prospects of LAMP technology in the future developments of herbal medicine identification and the challenges associated with its application.",2016 Dec 26,"['Li, Jing-jian', 'Xiong, Chao', 'Liu, Yue', 'Liang, Jun-song', 'Zhou, Xing-wen']",Front Plant Sci,,,True
45d2d838cb3d5ae2dabd7bb7c82329b398d1c65f,PMC,A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection,http://dx.doi.org/10.1186/1471-2334-4-34,PMC518965,15357874,CC BY,"BACKGROUND: The molecular basis of severe acute respiratory syndrome (SARS) coronavirus (CoV) induced pathology is still largely unclear. Many SARS patients suffer respiratory distress brought on by interstitial infiltration and frequently show peripheral blood lymphopenia and occasional leucopenia. One possible cause of this could be interstitial inflammation, following a localized host response. In this study, we therefore examine the immune response of SARS-CoV in human peripheral blood mononuclear cells (PBMCs) over the first 24 hours. METHODS: PBMCs from normal healthy donors were inoculated in vitro with SARS-CoV and the viral replication kinetics was studied by real-time quantitative assays. SARS-CoV specific gene expression changes were examined by high-density oligonucleotide array analysis. RESULTS: We observed that SARS-CoV was capable of infecting and replicating in PBMCs and the kinetics of viral replication was variable among the donors. SARS-CoV antibody binding assays indicated that SARS specific antibodies inhibited SARS-CoV viral replication. Array data showed monocyte-macrophage cell activation, coagulation pathway upregulation and cytokine production together with lung trafficking chemokines such as IL8 and IL17, possibly activated through the TLR9 signaling pathway; that mimicked clinical features of the disease. CONCLUSIONS: The identification of human blood mononuclear cells as a direct target of SARS-CoV in the model system described here provides a new insight into disease pathology and a tool for investigating the host response and mechanisms of pathogenesis.",2004 Sep 9,"['Ng, Lisa FP', 'Hibberd, Martin L', 'Ooi, Eng-Eong', 'Tang, Kin-Fai', 'Neo, Soek-Ying', 'Tan, Jenny', 'Krishna Murthy, Karuturi R', 'Vega, Vinsensius B', 'Chia, Jer-Ming', 'Liu, Edison T', 'Ren, Ee-Chee']",BMC Infect Dis,,,True
1b57217c350c53ef4e96049f9f35bf07b8089976,PMC,A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection,http://dx.doi.org/10.1186/1471-2334-4-34,PMC518965,15357874,CC BY,"BACKGROUND: The molecular basis of severe acute respiratory syndrome (SARS) coronavirus (CoV) induced pathology is still largely unclear. Many SARS patients suffer respiratory distress brought on by interstitial infiltration and frequently show peripheral blood lymphopenia and occasional leucopenia. One possible cause of this could be interstitial inflammation, following a localized host response. In this study, we therefore examine the immune response of SARS-CoV in human peripheral blood mononuclear cells (PBMCs) over the first 24 hours. METHODS: PBMCs from normal healthy donors were inoculated in vitro with SARS-CoV and the viral replication kinetics was studied by real-time quantitative assays. SARS-CoV specific gene expression changes were examined by high-density oligonucleotide array analysis. RESULTS: We observed that SARS-CoV was capable of infecting and replicating in PBMCs and the kinetics of viral replication was variable among the donors. SARS-CoV antibody binding assays indicated that SARS specific antibodies inhibited SARS-CoV viral replication. Array data showed monocyte-macrophage cell activation, coagulation pathway upregulation and cytokine production together with lung trafficking chemokines such as IL8 and IL17, possibly activated through the TLR9 signaling pathway; that mimicked clinical features of the disease. CONCLUSIONS: The identification of human blood mononuclear cells as a direct target of SARS-CoV in the model system described here provides a new insight into disease pathology and a tool for investigating the host response and mechanisms of pathogenesis.",2004 Sep 9,"['Ng, Lisa FP', 'Hibberd, Martin L', 'Ooi, Eng-Eong', 'Tang, Kin-Fai', 'Neo, Soek-Ying', 'Tan, Jenny', 'Krishna Murthy, Karuturi R', 'Vega, Vinsensius B', 'Chia, Jer-Ming', 'Liu, Edison T', 'Ren, Ee-Chee']",BMC Infect Dis,,,False
5bb2fe58be63844d5b13a6b0cacd3ec2c80d3cb3,PMC,Replicon RNA Viral Vectors as Vaccines,http://dx.doi.org/10.3390/vaccines4040039,PMC5192359,27827980,CC BY,"Single-stranded RNA viruses of both positive and negative polarity have been used as vectors for vaccine development. In this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. Administration of replicon RNA vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. Immunization of mice, chicken, pigs and primates with virus-like particles, naked RNA or layered DNA/RNA plasmids has provided protection against challenges with lethal doses of infectious agents and administered tumor cells. Both prophylactic and therapeutic efficacy has been achieved in cancer immunotherapy. Moreover, recombinant particles and replicon RNAs have been encapsulated by liposomes to improve delivery and targeting. Replicon RNA vectors have also been subjected to clinical trials. Overall, immunization with self-replicating RNA viruses provides high transient expression levels of antigens resulting in generation of neutralizing antibody responses and protection against lethal challenges under safe conditions.",2016 Nov 7,"Lundstrom, Kenneth",Vaccines (Basel),,,True
fc524fbd93be3db421c75c589e2299524a75fa26,PMC,"Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models",http://dx.doi.org/10.3390/v8120322,PMC5192383,27916837,CC BY,"Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres. We demonstrate that chloroquine reduces the number of ZIKV-infected cells in vitro, and inhibits virus production and cell death promoted by ZIKV infection without cytotoxic effects. In addition, chloroquine treatment partially reveres morphological changes induced by ZIKV infection in mouse neurospheres.",2016 Nov 29,"['Delvecchio, Rodrigo', 'Higa, Luiza M.', 'Pezzuto, Paula', 'Valadão, Ana Luiza', 'Garcez, Patrícia P.', 'Monteiro, Fábio L.', 'Loiola, Erick C.', 'Dias, André A.', 'Silva, Fábio J. M.', 'Aliota, Matthew T.', 'Caine, Elizabeth A.', 'Osorio, Jorge E.', 'Bellio, Maria', 'O’Connor, David H.', 'Rehen, Stevens', 'de Aguiar, Renato Santana', 'Savarino, Andrea', 'Campanati, Loraine', 'Tanuri, Amilcar']",Viruses,,,True
044b6504465e3d1b00fcc328c6731bcd034b1691,PMC,Comparative Proteome Analysis of Porcine Jejunum Tissues in Response to a Virulent Strain of Porcine Epidemic Diarrhea Virus and Its Attenuated Strain,http://dx.doi.org/10.3390/v8120323,PMC5192384,27916855,CC BY,"Porcine epidemic diarrhea virus (PEDV), a predominant cause of acute enteric infection, leads to severe dehydrating diarrhea and mortality in piglets all over the world. A virulent PEDV YN13 strain, isolated in our laboratory, was attenuated to yield an attenuated PEDV strain YN144. To better understand the pathogenesis mechanism and the virus-host interaction during infection with both PEDV YN13 and YN144 strains, a comparative proteomic analysis was carried out to investigate the proteomic changes produced in the primary target organ, using isobaric tags for relative and absolute quantitation (iTRAQ) labeling, followed by liquid chromatography tandem-mass spectrometry (LC-MS/MS). A total of 269 and 301 differently expressed proteins (DEPs) were identified in the jejunum tissues of the piglets inoculated with YN13 and YN144, respectively. Bioinformatics analysis revealed that these proteins were involved in stress responses, signal transduction, and the immune system. All of these involved interferon-stimulated genes (ISGs) which were up-regulated in jejunums by both of the PEDV-infected groups. Based on the comparative analysis, we proposed that different changes induced by YN13 and YN144 in heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), eukaryotic initiation factor 4G1 (eIF4G1), and some members in the heat shock protein (HSP) family, may be responsible for differences in their pathogenicity.",2016 Nov 29,"['Li, Zhonghua', 'Chen, Fangzhou', 'Ye, Shiyi', 'Guo, Xiaozhen', 'Muhanmmad Memon, Atta', 'Wu, Meizhou', 'He, Qigai']",Viruses,,,True
2ace5853970e68deefd9800fdd135a266237884a,PMC,Characterization of an Immunodominant Epitope in the Endodomain of the Coronavirus Membrane Protein,http://dx.doi.org/10.3390/v8120327,PMC5192388,27973413,CC BY,"The coronavirus membrane (M) protein acts as a dominant immunogen and is a major player in virus assembly. In this study, we prepared two monoclonal antibodies (mAbs; 1C3 and 4C7) directed against the transmissible gastroenteritis virus (TGEV) M protein. The 1C3 and 4C7 mAbs both reacted with the native TGEV M protein in western blotting and immunofluorescence (IFA) assays. Two linear epitopes, 243YSTEART249 (1C3) and 243YSTEARTDNLSEQEKLLHMV262 (4C7), were identified in the endodomain of the TGEV M protein. The 1C3 mAb can be used for the detection of the TGEV M protein in different assays. An IFA method for the detection of TGEV M protein was optimized using mAb 1C3. Furthermore, the ability of the epitope identified in this study to stimulate antibody production was also evaluated. An immunodominant epitope in the TGEV membrane protein endodomain was identified. The results of this study have implications for further research on TGEV replication.",2016 Dec 10,"['Dong, Hui', 'Zhang, Xin', 'Shi, Hongyan', 'Chen, Jianfei', 'Shi, Da', 'Zhu, Yunnuan', 'Feng, Li']",Viruses,,,True
2a246ea75b64133cf7210fa8971a6d43917da132,PMC,Pharmacokinetics of the Antiviral Lectin Griffithsin Administered by Different Routes Indicates Multiple Potential Uses,http://dx.doi.org/10.3390/v8120331,PMC5192392,27999325,CC BY,"Griffithsin (GRFT) is a red alga-derived lectin with demonstrated broad spectrum antiviral activity against enveloped viruses, including severe acute respiratory syndrome–Coronavirus (SARS-CoV), Japanese encephalitis virus (JEV), hepatitis C virus (HCV), and herpes simplex virus-2 (HSV-2). However, its pharmacokinetic profile remains largely undefined. Here, Sprague Dawley rats were administered a single dose of GRFT at 10 or 20 mg/kg by intravenous, oral, and subcutaneous routes, respectively, and serum GRFT levels were measured at select time points. In addition, the potential for systemic accumulation after oral dosing was assessed in rats after 10 daily treatments with GRFT (20 or 40 mg/kg). We found that parenterally-administered GRFT in rats displayed a complex elimination profile, which varied according to administration routes. However, GRFT was not orally bioavailable, even after chronic treatment. Nonetheless, active GRFT capable of neutralizing HIV-Env pseudoviruses was detected in rat fecal extracts after chronic oral dosing. These findings support further evaluation of GRFT for pre-exposure prophylaxis against emerging epidemics for which specific therapeutics are not available, including systemic and enteric infections caused by susceptible enveloped viruses. In addition, GRFT should be considered for antiviral therapy and the prevention of rectal transmission of HIV-1 and other susceptible viruses.",2016 Dec 17,"['Barton, Christopher', 'Kouokam, J. Calvin', 'Hurst, Harrell', 'Palmer, Kenneth E.']",Viruses,,,True
9be5f21d6d5bc49f664d559e63c68f6410a39ae4,PMC,Equine Immunoglobulin and Equine Neutralizing F(ab′)(2) Protect Mice from West Nile Virus Infection,http://dx.doi.org/10.3390/v8120332,PMC5192393,27999340,CC BY,"West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab′)(2) fragments from horses immunized with the WNV virus-like particles (VLP) expressing the WNV M and E proteins. Immune equine F(ab′)(2) fragments and immune horse sera efficiently neutralized WNV infection in tissue culture. The passive transfer of equine immune antibodies significantly accelerated the virus clearance in the spleens and brains of WNV infected mice, and reduced mortality. Thus, equine immunoglobulin or equine neutralizing F(ab′)(2) passive immunotherapy is a potential strategy for the prophylactic or therapeutic treatment of patients infected with WNV.",2016 Dec 18,"['Cui, Jiannan', 'Zhao, Yongkun', 'Wang, Hualei', 'Qiu, Boning', 'Cao, Zengguo', 'Li, Qian', 'Zhang, Yanbo', 'Yan, Feihu', 'Jin, Hongli', 'Wang, Tiecheng', 'Sun, Weiyang', 'Feng, Na', 'Gao, Yuwei', 'Sun, Jing', 'Wang, Yanqun', 'Perlman, Stanley', 'Zhao, Jincun', 'Yang, Songtao', 'Xia, Xianzhu']",Viruses,,,True
4564fff695ff930d022c77efecde703856943b7f,PMC,Transspecies Transmission of Gammaretroviruses and the Origin of the Gibbon Ape Leukaemia Virus (GaLV) and the Koala Retrovirus (KoRV),http://dx.doi.org/10.3390/v8120336,PMC5192397,27999419,CC BY,"Transspecies transmission of retroviruses is a frequent event, and the human immunodeficiency virus-1 (HIV-1) is a well-known example. The gibbon ape leukaemia virus (GaLV) and koala retrovirus (KoRV), two gammaretroviruses, are also the result of a transspecies transmission, however from a still unknown host. Related retroviruses have been found in Southeast Asian mice although the sequence similarity was limited. Viruses with a higher sequence homology were isolated from Melomys burtoni, the Australian and Indonesian grassland melomys. However, only the habitats of the koalas and the grassland melomys in Australia are overlapping, indicating that the melomys virus may not be the precursor of the GaLV. Viruses closely related to GaLV/KoRV were also detected in bats. Therefore, given the fact that the habitats of the gibbons in Thailand and the koalas in Australia are far away, and that bats are able to fly over long distances, the hypothesis that retroviruses of bats are the origin of GaLV and KoRV deserves consideration. Analysis of previous transspecies transmissions of retroviruses may help to evaluate the potential of transmission of related retroviruses in the future, e.g., that of porcine endogenous retroviruses (PERVs) during xenotransplantation using pig cells, tissues or organs.",2016 Dec 20,"Denner, Joachim",Viruses,,,True
24c739b85e7c9082d00e9680cf7a99070c427d55,PMC,Resistance of Aerosolized Bacterial Viruses to Four Germicidal Products,http://dx.doi.org/10.1371/journal.pone.0168815,PMC5193356,28030577,CC BY,"Viral diseases can spread through a variety of routes including aerosols. Yet, limited data are available on the efficacy of aerosolized chemicals to reduce viral loads in the air. Bacteriophages (phages) are often used as surrogates for hazardous viruses in aerosol studies because they are inexpensive, easy to handle, and safe for laboratory workers. Moreover, several of these bacterial viruses display physical characteristics similar to pathogenic human and animal viruses, like morphological size, type of nucleic acids, capsid morphology, and the presence of an envelope. In this study, the efficacy of four chemicals was evaluated on four airborne phages at two different relative humidity levels. Non-tailed bacteriophages MS2 (single-stranded RNA), ϕ6 (double-stranded RNA, enveloped), PR772 (double-stranded DNA), and ϕX174 (single-stranded DNA) were first aerosolized in a 55L rotative environmental chamber at 19°C with 25% and 50% relative humidity. Then, hydrogen peroxide, Eugenol (phenylpropene used in commercial perfumes and flavorings), Mist(®) (automobile disinfectant containing Triethylene glycol), and Pledge(®) (multisurface disinfectant containing Isopropanol, n-Alkyl Dimethyl Benzyl Amonium Chlorides, and n-Alkyl Dimethyl Ethylbenzyl Ammonium Chloride) were nebulized with the phages using a separate nebulizer. Aerosols were maintained in suspension during 10 minutes, 1 hour, and 2 hours. Viral aerosols were sampled using an SKC BioSampler and samples were analyzed using qPCR and plaque assays. The resistance levels of the four phages varied depending on the relative humidity (RH) and germicidal products tested. Phage MS2 was the most stable airborne virus under the environmental conditions tested while phage PR772 was the least stable. Pledge(®) and Eugenol reduced the infectivity of all airborne phages tested. At 25% RH, Pledge(®) and Eugenol were more effective at reducing infectivity of RNA phages ϕ6 and MS2. At 50% RH, Pledge(®) was the most effective agent against phage MS2. These findings illustrate that various airborne viruses should be tested to demonstrate the effectiveness of germicidal treatments. This research also provides a set of parameters for testing germicidal products in large-scale settings to reduce the risk of virus transmission.",2016 Dec 28,"['Turgeon, Nathalie', 'Michel, Kevin', 'Ha, Thi-Lan', 'Robine, Enric', 'Moineau, Sylvain', 'Duchaine, Caroline']",PLoS One,,,True
48106886ec5b19e6cc62abf552ff3529f1d8aca3,PMC,The presence of fever in adults with influenza and other viral respiratory infections,http://dx.doi.org/10.1017/S0950268816002181,PMC5197931,27691995,CC BY,"We compared the rates of fever in adult subjects with laboratory-confirmed influenza and other respiratory viruses and examined the factors that predict fever in adults. Symptom data on 158 healthcare workers (HCWs) with a laboratory-confirmed respiratory virus infection were collected using standardized data collection forms from three separate studies. Overall, the rate of fever in confirmed viral respiratory infections in adult HCWs was 23·4% (37/158). Rates varied by virus: human rhinovirus (25·3%, 19/75), influenza A virus (30%, 3/10), coronavirus (28·6%, 2/7), human metapneumovirus (28·6%, 2/7), respiratory syncytial virus (14·3%, 4/28) and parainfluenza virus (8·3%, 1/12). Smoking [relative risk (RR) 4·65, 95% confidence interval (CI) 1·33–16·25] and co-infection with two or more viruses (RR 4·19, 95% CI 1·21–14·52) were significant predictors of fever. Fever is less common in adults with confirmed viral respiratory infections, including influenza, than described in children. More than 75% of adults with a viral respiratory infection do not have fever, which is an important finding for clinical triage of adult patients with respiratory infections. The accepted definition of ‘influenza-like illness’ includes fever and may be insensitive for surveillance when high case-finding is required. A more sensitive case definition could be used to identify adult cases, particularly in event of an emerging viral infection.",2017 Jan 3,"['CHUGHTAI, A. A.', 'WANG, Q.', 'DUNG, T. C.', 'MACINTYRE, C. R.']",Epidemiol Infect,,,True
430213ca4c52874f7082c2a1d1c3117187e41dae,PMC,Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses,http://dx.doi.org/10.3390/ph9040078,PMC5198053,27999271,CC BY,"Appropriate diagnosis is the key factor for treatment of viral diseases. Time is the most important factor in rapidly developing and epidemiologically dangerous diseases, such as influenza, Ebola and SARS. Chronic viral diseases such as HIV-1 or HCV are asymptomatic or oligosymptomatic and the therapeutic success mainly depends on early detection of the infective agent. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against virus proteins. From a diagnostics point of view, aptamers are being designed as a bio-recognition element in diagnostic systems to detect viral proteins either in the blood (serum or plasma) or into infected cells. Another potential use of aptamers is for therapeutics of viral infections, interfering in the interaction between the virus and the host using aptamers targeting host-cell matrix receptors, or attacking the virus intracellularly, targeting proteins implicated in the viral replication cycle. In this paper, we review how aptamers working against viral proteins are discovered, with a focus on recent advances that improve the aptamers’ properties as a real tool for viral infection detection and treatment.",2016 Dec 16,"['González, Víctor M.', 'Martín, M. Elena', 'Fernández, Gerónimo', 'García-Sacristán, Ana']",Pharmaceuticals (Basel),,,True
25707e09aa87bb548138776e263ab037f4e6cda0,PMC,Heme Oxygenase-1-Expressing Dendritic Cells Promote Foxp3(+) Regulatory T Cell Differentiation and Induce Less Severe Airway Inflammation in Murine Models,http://dx.doi.org/10.1371/journal.pone.0168919,PMC5199094,28033400,CC BY,"Dendritic cells (DCs) are critical for instructing immune responses toward inflammatory or anti-inflammatory status. Heme oxygenase-1 (HO-1) is known for its cytoprotective effect against oxidative stress and inflammation, suggesting its immune regulatory role in allergic lung inflammation. HO-1 has been implicated in affecting DC maturation; however, its role in DC-mediated T-cell differentiation is unclear. In this study, we demonstrated that HO-1-expressing bone marrow-derived dendritic cells (BM-DCs) displayed tolerogenic phenotypes, including their resistance to lipopolysaccharide (LPS)-induced maturation, high level expression of IL-10, and low T-cell stimulatory activity. In addition, HO-1-expressing DCs were able to induce antigen-specific Foxp3(+) regulatory T cells (Treg) differentiation in vitro and in vivo. Also, HO-1-expressing DCs modulated the severity of lung inflammatory responses in two murine models of airway inflammation. This study provided evidence supporting the role of HO-1-expressing DCs in tolerance induction and as a potential therapeutic target for allergic asthma as well as other inflammatory diseases.",2016 Dec 29,"['Wong, Tzu-Hsuan', 'Chen, Hung-An', 'Gau, Rung-Jiun', 'Yen, Jeng-Hsien', 'Suen, Jau-Ling']",PLoS One,,,True
0f52f6ec3e15cc1cc45803c3cb81618d5ee82b7a,PMC,"Coherence of Influenza Surveillance Data across Different Sources and Age Groups, Beijing, China, 2008-2015",http://dx.doi.org/10.1371/journal.pone.0169199,PMC5201231,28036373,CC BY,"Influenza is active during the winter and spring in the city of Beijing, which has a typical temperate climate with four clear distinct seasons. The clinical and laboratory surveillance data for influenza have been used to construct critical indicators for influenza activities in the community, and previous studies have reported varying degrees of association between laboratory-confirmed influenza specimens and outpatient consultation rates of influenza-like illness in subtropical cities. However, few studies have reported on this issue for cities in temperate regions, especially in developing countries. Furthermore, the mechanism behind age-specific seasonal epidemics remains unresolved, although it has been widely discussed. We utilized a wavelet analysis method to monitor the coherence of weekly percentage of laboratory-confirmed influenza specimens with the weekly outpatient consultation rates of influenza-like illness in Beijing, China. We first examined the seasonal pattern of laboratory-confirmed cases of influenza A (subtyped into seasonal A(H1N1) and A(H3N2) and pandemic virus A(H1N1) pdm09) and influenza B separately within the period from 2008–2015; then, we detected the coherence of clinical and laboratory surveillance data in this district, specially examining weekly time series of age-specific epidemics of influenza-like illnesses in the whole study period for three age categories (age 0–5, 5–15 and 25–60). We found that influenza A and B were both active in winter but were not always seasonally synchronous in Beijing. Synchronization between age ranges was found in most epidemic peaks from 2008–2015. Our findings suggested that peaks of influenza-like illness in individuals aged 0–5 and 5–15 years consistently appeared ahead of those of adults, implying the possibility that schoolchildren may lead epidemic fluctuations.",2016 Dec 30,"['Wu, Zhenyu', 'Sun, Xiaoyu', 'Chu, Yanhui', 'Sun, Jingyi', 'Qin, Guoyou', 'Yang, Lin', 'Qin, Jingning', 'Xiao, Zheng', 'Ren, Jian', 'Qin, Di', 'Wang, Xiling', 'Zheng, Xueying']",PLoS One,,,True
eb6e2916b4a94b8c8a3e7d58f70158dc04191503,PMC,"Knowledge, Attitudes and Behaviours of Healthcare Workers in the Kingdom of Saudi Arabia to MERS Coronavirus and Other Emerging Infectious Diseases",http://dx.doi.org/10.3390/ijerph13121214,PMC5201355,27929452,CC BY,"Background: The Kingdom of Saudi Arabia has experienced a prolonged outbreak of Middle East Respiratory Syndrome (MERS) coronavirus since 2012. Healthcare workers (HCWs) form a significant risk group for infection. Objectives: The aim of this survey was to assess the knowledge, attitudes, infection control practices and educational needs of HCWs in the Kingdom of Saudi Arabia to MERS coronavirus and other emerging infectious diseases. Methods: 1500 of HCWs from Saudi Ministry of Health were invited to fill a questionnaire developed to cover the survey objectives from 9 September 2015 to 8 November 2015. The response rate was about 81%. Descriptive statistics was used to summarise the responses. Results: 1216 HCWs were included in this survey. A total of 56.5% were nurses and 22% were physicians. The most common sources of MERS-coronavirus (MERS-CoV) information were the Ministry of Health (MOH) memo (74.3%). Only (47.6%) of the physicians, (30.4%) of the nurses and (29.9%) of the other HCWs were aware that asymptomatic MERS-CoV was described. Around half of respondents who having been investigated for MERS-CoV reported that their work performance decreased while they have suspicion of having MERS-CoV and almost two thirds reported having psychological problems during this period. Almost two thirds of the HCWs (61.2%) reported anxiety about contracting MERS-CoV from patients. Conclusions: The knowledge about emerging infectious diseases was poor and there is need for further education and training programs particularly in the use of personal protective equipment, isolation and infection control measures. The self-reported infection control practices were sub-optimal and seem to be overestimated.",2016 Dec 6,"['Alsahafi, Abdullah J.', 'Cheng, Allen C.']",Int J Environ Res Public Health,,,True
7c8f40872fb6e8d5289fec4b0573cc22e15fa180,PMC,Military-civilian cooperative emergency response to infectious disease prevention and control in China,http://dx.doi.org/10.1186/s40779-016-0109-y,PMC5203723,28050261,CC BY,"In recent years, the incidence of severe infectious diseases has increased, and the number of emerging infectious diseases continues to increase. The Chinese government and military forces have paid a great deal of attention to infectious disease prevention and control, and using military-civilian cooperation, they have successfully prevented numerous severe epidemic situations, such as severe acute respiratory syndrome (SARS), influenza A (H1N1), avian influenza H5N1 and H7N9, and Ebola hemorrhagic fever, while actively maintained public health, economic development, and national construction. This paper focuses on the mechanisms of the military-cooperative emergency response to infectious diseases--the joint working mechanism, the information-sharing mechanism, the research collaboration mechanism, and the joint disposal mechanism--and presents a sorted summary of the practices and experiences of cooperative emergency responses to infectious diseases. In the future, the Chinese military and the civilian sector will further strengthen the cooperative joint command system and emergency rescue force and will reinforce their collaborative information-sharing platform and technical equipment system to further improve military-civilian collaborative emergency infectious diseases disposal, advance the level of infectious disease prevention and control, and maintain public health.",2016 Dec 30,"['Ma, Hui', 'Dong, Ji-Ping', 'Zhou, Na', 'Pu, Wei']",Mil Med Res,,,True
f7ddd78bba691e9200cece8a05b3486fab895885,PMC,Role of Eukaryotic Initiation Factors during Cellular Stress and Cancer Progression,http://dx.doi.org/10.1155/2016/8235121,PMC5204094,28083147,CC BY,"Protein synthesis can be segmented into distinct phases comprising mRNA translation initiation, elongation, and termination. Translation initiation is a highly regulated and rate-limiting step of protein synthesis that requires more than 12 eukaryotic initiation factors (eIFs). Extensive evidence shows that the transcriptome and corresponding proteome do not invariably correlate with each other in a variety of contexts. In particular, translation of mRNAs specific to angiogenesis, tumor development, and apoptosis is altered during physiological and pathophysiological stress conditions. In cancer cells, the expression and functions of eIFs are hampered, resulting in the inhibition of global translation and enhancement of translation of subsets of mRNAs by alternative mechanisms. A precise understanding of mechanisms involving eukaryotic initiation factors leading to differential protein expression can help us to design better strategies to diagnose and treat cancer. The high spatial and temporal resolution of translation control can have an immediate effect on the microenvironment of the cell in comparison with changes in transcription. The dysregulation of mRNA translation mechanisms is increasingly being exploited as a target to treat cancer. In this review, we will focus on this context by describing both canonical and noncanonical roles of eIFs, which alter mRNA translation.",2016 Dec 19,"['Sharma, Divya Khandige', 'Bressler, Kamiko', 'Patel, Harshil', 'Balasingam, Nirujah', 'Thakor, Nehal']",J Nucleic Acids,,,True
37bc284af4f2f731792f44339253abc79c6d2782,PMC,Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity,http://dx.doi.org/10.3389/fimmu.2016.00662,PMC5206486,28096803,CC BY,"Innate immunity is the first line of defense against invading pathogens. Rapid and efficient detection of pathogen-associated molecular patterns via pattern-recognition receptors is essential for the host to mount defensive and protective responses. Retinoic acid-inducible gene-I (RIG-I) is critical in triggering antiviral and inflammatory responses for the control of viral replication in response to cytoplasmic virus-specific RNA structures. Upon viral RNA recognition, RIG-I recruits the mitochondrial adaptor protein mitochondrial antiviral signaling protein, which leads to a signaling cascade that coordinates the induction of type I interferons (IFNs), as well as a large variety of antiviral interferon-stimulated genes. The RIG-I activation is tightly regulated via various posttranslational modifications for the prevention of aberrant innate immune signaling. By contrast, viruses have evolved mechanisms of evasion, such as sequestrating viral structures from RIG-I detections and targeting receptor or signaling molecules for degradation. These virus–host interactions have broadened our understanding of viral pathogenesis and provided insights into the function of the RIG-I pathway. In this review, we summarize the recent advances regarding RIG-I pathogen recognition and signaling transduction, cell-intrinsic control of RIG-I activation, and the viral antagonism of RIG-I signaling.",2017 Jan 3,"['Liu, Yiliu', 'Olagnier, David', 'Lin, Rongtuan']",Front Immunol,,,True
4328e18bdf9b52875c87f3f5ddb1911636a192d2,PMC,"Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome",http://dx.doi.org/10.3389/fimmu.2016.00535,PMC5206578,28096800,CC BY,"Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Previous studies have identified interferon-induced transmembrane proteins (IFITMs) as an interferon-stimulated gene family. However, the role of IFITMs in HTNV infection is unclear. In this study, we observed that IFITM3 single nucleotide polymorphisms (SNP) rs12252 C allele and CC genotype associated with the disease severity and HTNV load in the plasma of HFRS patients. In vitro experiments showed that the truncated protein produced by the rs12252 C allele exhibited an impaired anti-HTNV activity. We also proved that IFITM3 was able to inhibit HTNV infection in both HUVEC and A549 cells by overexpression and RNAi assays, likely via a mechanism of inhibiting virus entry demonstrated by binding and entry assay. Localization of IFITM3 in late endosomes was also observed. In addition, we demonstrated that the transcription of IFITM3 is negatively regulated by an lncRNA negative regulator of interferon response (NRIR). Taken together, we conclude that IFITM3, negatively regulated by NRIR, inhibits HTNV infection, and its SNP rs12252 correlates with the plasma HTNV load and the disease severity of patients with HFRS.",2017 Jan 3,"['Xu-yang, Zheng', 'Pei-yu, Bian', 'Chuan-tao, Ye', 'Wei, Ye', 'Hong-wei, Ma', 'Kang, Tang', 'Chun-mei, Zhang', 'Ying-feng, Lei', 'Xin, Wei', 'Ping-zhong, Wang', 'Chang-xing, Huang', 'Xue-fan, Bai', 'Ying, Zhang', 'Zhan-sheng, Jia']",Front Immunol,,,True
76260c67421abbf69da3c4b0c75204190188a2cc,PMC,"Nucleocapsid Interacts with NPM1 and Protects it from Proteolytic Cleavage, Enhancing Cell Survival, and is Involved in PEDV Growth",http://dx.doi.org/10.1038/srep39700,PMC5206633,28045037,CC BY,"Porcine epidemic diarrhea virus (PEDV) replicates in the cytoplasm of infected cells, but its nucleocapsid (N) protein localizes specifically to the nucleolus. The mechanism of nuclear translocation, and whether N protein associates with particular nucleolar components, is unknown. In this study, we confirm that a nucleolar phosphoprotein nucleophosmin (NPM1) interacts and co-localizes with the N protein in the nucleolus. In vitro binding studies indicated that aa 148–294 of N and aa 118–188 of NPM1 were required for binding. Interestingly, N protein importation into the nucleolus is independent of the ability of NPM1 to shuttle between the nucleus and the cytoplasm. Furthermore, overexpression of NPM1 promoted PEDV growth, while knockdown of NPM1 suppressed PEDV growth. In addition, binding of N protein to NPM1 protects it from proteolytic degradation by caspase-3, leading to increased cell survival. Taken together, our studies demonstrate a specific interaction of the N protein with the host cell protein NPM1 in the nucleolus. The results suggest potential linkages among viral strategies for the regulation of cell survival activities, possibly through an interaction of N protein with NPM1 which prevents its proteolytic cleavage and enhances cell survival, thus ultimately promoting the replication of PEDV.",2017 Jan 3,"['Shi, Da', 'Shi, Hongyan', 'Sun, Dongbo', 'Chen, Jianfei', 'Zhang, Xin', 'Wang, Xiaobo', 'Zhang, Jialin', 'Ji, Zhaoyang', 'Liu, Jianbo', 'Cao, Liyan', 'Zhu, Xiangdong', 'Yuan, Jing', 'Dong, Hui', 'Wang, Xin', 'Chang, Tiecheng', 'Liu, Ye', 'Feng, Li']",Sci Rep,,,True
77e4762b5cc01adc2c17ddfe8e4de0a8036f4821,PMC,"Nucleocapsid Interacts with NPM1 and Protects it from Proteolytic Cleavage, Enhancing Cell Survival, and is Involved in PEDV Growth",http://dx.doi.org/10.1038/srep39700,PMC5206633,28045037,CC BY,"Porcine epidemic diarrhea virus (PEDV) replicates in the cytoplasm of infected cells, but its nucleocapsid (N) protein localizes specifically to the nucleolus. The mechanism of nuclear translocation, and whether N protein associates with particular nucleolar components, is unknown. In this study, we confirm that a nucleolar phosphoprotein nucleophosmin (NPM1) interacts and co-localizes with the N protein in the nucleolus. In vitro binding studies indicated that aa 148–294 of N and aa 118–188 of NPM1 were required for binding. Interestingly, N protein importation into the nucleolus is independent of the ability of NPM1 to shuttle between the nucleus and the cytoplasm. Furthermore, overexpression of NPM1 promoted PEDV growth, while knockdown of NPM1 suppressed PEDV growth. In addition, binding of N protein to NPM1 protects it from proteolytic degradation by caspase-3, leading to increased cell survival. Taken together, our studies demonstrate a specific interaction of the N protein with the host cell protein NPM1 in the nucleolus. The results suggest potential linkages among viral strategies for the regulation of cell survival activities, possibly through an interaction of N protein with NPM1 which prevents its proteolytic cleavage and enhances cell survival, thus ultimately promoting the replication of PEDV.",2017 Jan 3,"['Shi, Da', 'Shi, Hongyan', 'Sun, Dongbo', 'Chen, Jianfei', 'Zhang, Xin', 'Wang, Xiaobo', 'Zhang, Jialin', 'Ji, Zhaoyang', 'Liu, Jianbo', 'Cao, Liyan', 'Zhu, Xiangdong', 'Yuan, Jing', 'Dong, Hui', 'Wang, Xin', 'Chang, Tiecheng', 'Liu, Ye', 'Feng, Li']",Sci Rep,,,False
367af6bb9a8bbda02206506a819656bb6f14ce4c,PMC,Logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model,http://dx.doi.org/10.1186/1471-2458-4-34,PMC520756,15298713,CC BY,"BACKGROUND: Previous smallpox ring vaccination models based on contact tracing over a network suggest that ring vaccination would be effective, but have not explicitly included response logistics and limited numbers of vaccinators. METHODS: We developed a continuous-time stochastic simulation of smallpox transmission, including network structure, post-exposure vaccination, vaccination of contacts of contacts, limited response capacity, heterogeneity in symptoms and infectiousness, vaccination prior to the discontinuation of routine vaccination, more rapid diagnosis due to public awareness, surveillance of asymptomatic contacts, and isolation of cases. RESULTS: We found that even in cases of very rapidly spreading smallpox, ring vaccination (when coupled with surveillance) is sufficient in most cases to eliminate smallpox quickly, assuming that 95% of household contacts are traced, 80% of workplace or social contacts are traced, and no casual contacts are traced, and that in most cases the ability to trace 1–5 individuals per day per index case is sufficient. If smallpox is assumed to be transmitted very quickly to contacts, it may at times escape containment by ring vaccination, but could be controlled in these circumstances by mass vaccination. CONCLUSIONS: Small introductions of smallpox are likely to be easily contained by ring vaccination, provided contact tracing is feasible. Uncertainties in the nature of bioterrorist smallpox (infectiousness, vaccine efficacy) support continued planning for ring vaccination as well as mass vaccination. If initiated, ring vaccination should be conducted without delays in vaccination, should include contacts of contacts (whenever there is sufficient capacity) and should be accompanied by increased public awareness and surveillance.",2004 Aug 6,"['Porco, Travis C', 'Holbrook, Karen A', 'Fernyak, Susan E', 'Portnoy, Diane L', 'Reiter, Randy', 'Aragón, Tomás J']",BMC Public Health,,,True
638e94413019416e1f60f942e1870ac8e9cc4a3a,PMC,Logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model,http://dx.doi.org/10.1186/1471-2458-4-34,PMC520756,15298713,CC BY,"BACKGROUND: Previous smallpox ring vaccination models based on contact tracing over a network suggest that ring vaccination would be effective, but have not explicitly included response logistics and limited numbers of vaccinators. METHODS: We developed a continuous-time stochastic simulation of smallpox transmission, including network structure, post-exposure vaccination, vaccination of contacts of contacts, limited response capacity, heterogeneity in symptoms and infectiousness, vaccination prior to the discontinuation of routine vaccination, more rapid diagnosis due to public awareness, surveillance of asymptomatic contacts, and isolation of cases. RESULTS: We found that even in cases of very rapidly spreading smallpox, ring vaccination (when coupled with surveillance) is sufficient in most cases to eliminate smallpox quickly, assuming that 95% of household contacts are traced, 80% of workplace or social contacts are traced, and no casual contacts are traced, and that in most cases the ability to trace 1–5 individuals per day per index case is sufficient. If smallpox is assumed to be transmitted very quickly to contacts, it may at times escape containment by ring vaccination, but could be controlled in these circumstances by mass vaccination. CONCLUSIONS: Small introductions of smallpox are likely to be easily contained by ring vaccination, provided contact tracing is feasible. Uncertainties in the nature of bioterrorist smallpox (infectiousness, vaccine efficacy) support continued planning for ring vaccination as well as mass vaccination. If initiated, ring vaccination should be conducted without delays in vaccination, should include contacts of contacts (whenever there is sufficient capacity) and should be accompanied by increased public awareness and surveillance.",2004 Aug 6,"['Porco, Travis C', 'Holbrook, Karen A', 'Fernyak, Susan E', 'Portnoy, Diane L', 'Reiter, Randy', 'Aragón, Tomás J']",BMC Public Health,,,False
55d7f70ed1547d9c2708ffb08ae515d54de510fb,PMC,Logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model,http://dx.doi.org/10.1186/1471-2458-4-34,PMC520756,15298713,CC BY,"BACKGROUND: Previous smallpox ring vaccination models based on contact tracing over a network suggest that ring vaccination would be effective, but have not explicitly included response logistics and limited numbers of vaccinators. METHODS: We developed a continuous-time stochastic simulation of smallpox transmission, including network structure, post-exposure vaccination, vaccination of contacts of contacts, limited response capacity, heterogeneity in symptoms and infectiousness, vaccination prior to the discontinuation of routine vaccination, more rapid diagnosis due to public awareness, surveillance of asymptomatic contacts, and isolation of cases. RESULTS: We found that even in cases of very rapidly spreading smallpox, ring vaccination (when coupled with surveillance) is sufficient in most cases to eliminate smallpox quickly, assuming that 95% of household contacts are traced, 80% of workplace or social contacts are traced, and no casual contacts are traced, and that in most cases the ability to trace 1–5 individuals per day per index case is sufficient. If smallpox is assumed to be transmitted very quickly to contacts, it may at times escape containment by ring vaccination, but could be controlled in these circumstances by mass vaccination. CONCLUSIONS: Small introductions of smallpox are likely to be easily contained by ring vaccination, provided contact tracing is feasible. Uncertainties in the nature of bioterrorist smallpox (infectiousness, vaccine efficacy) support continued planning for ring vaccination as well as mass vaccination. If initiated, ring vaccination should be conducted without delays in vaccination, should include contacts of contacts (whenever there is sufficient capacity) and should be accompanied by increased public awareness and surveillance.",2004 Aug 6,"['Porco, Travis C', 'Holbrook, Karen A', 'Fernyak, Susan E', 'Portnoy, Diane L', 'Reiter, Randy', 'Aragón, Tomás J']",BMC Public Health,,,False
be050658bf3b654ae5d9cbe62f6198e5c4932a95,PMC,"Recombinase Polymerase Amplification Assay—A Simple, Fast and Cost-Effective Alternative to Real Time PCR for Specific Detection of Feline Herpesvirus-1",http://dx.doi.org/10.1371/journal.pone.0166903,PMC5207716,28045956,CC BY,"Feline herpesvirus 1 (FHV-1), an enveloped dsDNA virus, is one of the major pathogens of feline upper respiratory tract disease (URTD) and ocular disease. Currently, polymerase chain reaction (PCR) remains the gold standard diagnostic tool for FHV-1 infection but is relatively expensive, requires well-equipped laboratories and is not suitable for field tests. Recombinase polymerase amplification (RPA), an isothermal gene amplification technology, has been explored for the molecular diagnosis of infectious diseases. In this study, an exo-RPA assay for FHV-1 detection was developed and validated. Primers targeting specifically the thymidine kinase (TK) gene of FHV-1 were designed. The RPA reaction was performed successfully at 39°C and the results were obtained within 20 min. Using different copy numbers of recombinant plasmid DNA that contains the TK gene as template, we showed the detection limit of exo-RPA was 10(2) copies DNA/reaction, the same as that of real time PCR. The exo-RPA assay did not cross-detect feline panleukopenia virus, feline calicivirus, bovine herpesvirus-1, pseudorabies virus or chlamydia psittaci, a panel of pathogens important in feline URTD or other viruses in Alphaherpesvirinae, demonstrating high specificity. The assay was validated by testing 120 nasal and ocular conjunctival swabs of cats, and the results were compared with those obtained with real-time PCR. Both assays provided the same testing results in the clinical samples. Compared with real time PCR, the exo-RPA assay uses less-complex equipment that is portable and the reaction is completed much faster. Additionally, commercial RPA reagents in vacuum-sealed pouches can tolerate temperatures up to room temperature for days without loss of activity, suitable for shipment and storage for field tests. Taken together, the exo-RPA assay is a simple, fast and cost-effective alternative to real time PCR, suitable for use in less advanced laboratories and for field detection of FHV-1 infection.",2017 Jan 3,"['Wang, Jianchang', 'Liu, Libing', 'Wang, Jinfeng', 'Sun, Xiaoxia', 'Yuan, Wanzhe']",PLoS One,,,True
7314f2ac32ead26d507b36cd305ffd76736f1007,PMC,Deep sequencing reveals persistence of cell-associated mumps vaccine virus in chronic encephalitis,http://dx.doi.org/10.1007/s00401-016-1629-y,PMC5209397,27770235,CC BY,"Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality. Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuV(JL5)) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID). This is the first confirmed report of MuV(JL5) associated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines. The diagnosis was only possible by deep sequencing of the brain biopsy. Sequence comparison of the vaccine batch to the MuV(JL5) isolated from brain identified biased hypermutation, particularly in the matrix gene, similar to those found in measles from cases of SSPE. The findings provide unique insights into the pathogenesis of paramyxovirus brain infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-016-1629-y) contains supplementary material, which is available to authorized users.",2017 Oct 21,"['Morfopoulou, Sofia', 'Mee, Edward T.', 'Connaughton, Sarah M.', 'Brown, Julianne R.', 'Gilmour, Kimberly', 'Chong, WK ‘Kling’', 'Duprex, W. Paul', 'Ferguson, Deborah', 'Hubank, Mike', 'Hutchinson, Ciaran', 'Kaliakatsos, Marios', 'McQuaid, Stephen', 'Paine, Simon', 'Plagnol, Vincent', 'Ruis, Christopher', 'Virasami, Alex', 'Zhan, Hong', 'Jacques, Thomas S.', 'Schepelmann, Silke', 'Qasim, Waseem', 'Breuer, Judith']",Acta Neuropathol,,,True
72aaf5f39ed048ee9ebda9af6fba6d6d12082e68,PMC,Versatility of Approximating Single-Particle Electron Microscopy Density Maps Using Pseudoatoms and Approximation-Accuracy Control,http://dx.doi.org/10.1155/2016/7060348,PMC5209604,28097146,CC BY,"Three-dimensional Gaussian functions have been shown useful in representing electron microscopy (EM) density maps for studying macromolecular structure and dynamics. Methods that require setting a desired number of Gaussian functions or a maximum number of iterations may result in suboptimal representations of the structure. An alternative is to set a desired error of approximation of the given EM map and then optimize the number of Gaussian functions to achieve this approximation error. In this article, we review different applications of such an approach that uses spherical Gaussian functions of fixed standard deviation, referred to as pseudoatoms. Some of these applications use EM-map normal mode analysis (NMA) with elastic network model (ENM) (applications such as predicting conformational changes of macromolecular complexes or exploring actual conformational changes by normal-mode-based analysis of experimental data) while some other do not use NMA (denoising of EM density maps). In applications based on NMA and ENM, the advantage of using pseudoatoms in EM-map coarse-grain models is that the ENM springs are easily assigned among neighboring grains thanks to their spherical shape and uniformed size. EM-map denoising based on the map coarse-graining was so far only shown using pseudoatoms as grains.",2016 Dec 21,"['Jonić, Slavica', 'Sorzano, Carlos Oscar S.']",Biomed Res Int,,,True
c936ef4688d255c47855066ca55d95f4dfc227e0,PMC,Universal and reusable virus deactivation system for respiratory protection,http://dx.doi.org/10.1038/srep39956,PMC5209731,28051158,CC BY,"Aerosolized pathogens are a leading cause of respiratory infection and transmission. Currently used protective measures pose potential risk of primary/secondary infection and transmission. Here, we report the development of a universal, reusable virus deactivation system by functionalization of the main fibrous filtration unit of surgical mask with sodium chloride salt. The salt coating on the fiber surface dissolves upon exposure to virus aerosols and recrystallizes during drying, destroying the pathogens. When tested with tightly sealed sides, salt-coated filters showed remarkably higher filtration efficiency than conventional mask filtration layer, and 100% survival rate was observed in mice infected with virus penetrated through salt-coated filters. Viruses captured on salt-coated filters exhibited rapid infectivity loss compared to gradual decrease on bare filters. Salt-coated filters proved highly effective in deactivating influenza viruses regardless of subtypes and following storage in harsh environmental conditions. Our results can be applied in obtaining a broad-spectrum, airborne pathogen prevention device in preparation for epidemic and pandemic of respiratory diseases.",2017 Jan 4,"['Quan, Fu-Shi', 'Rubino, Ilaria', 'Lee, Su-Hwa', 'Koch, Brendan', 'Choi, Hyo-Jick']",Sci Rep,,,True
a606413c3dd48c1755b453abeaa1c62702aba67e,PMC,Universal and reusable virus deactivation system for respiratory protection,http://dx.doi.org/10.1038/srep39956,PMC5209731,28051158,CC BY,"Aerosolized pathogens are a leading cause of respiratory infection and transmission. Currently used protective measures pose potential risk of primary/secondary infection and transmission. Here, we report the development of a universal, reusable virus deactivation system by functionalization of the main fibrous filtration unit of surgical mask with sodium chloride salt. The salt coating on the fiber surface dissolves upon exposure to virus aerosols and recrystallizes during drying, destroying the pathogens. When tested with tightly sealed sides, salt-coated filters showed remarkably higher filtration efficiency than conventional mask filtration layer, and 100% survival rate was observed in mice infected with virus penetrated through salt-coated filters. Viruses captured on salt-coated filters exhibited rapid infectivity loss compared to gradual decrease on bare filters. Salt-coated filters proved highly effective in deactivating influenza viruses regardless of subtypes and following storage in harsh environmental conditions. Our results can be applied in obtaining a broad-spectrum, airborne pathogen prevention device in preparation for epidemic and pandemic of respiratory diseases.",2017 Jan 4,"['Quan, Fu-Shi', 'Rubino, Ilaria', 'Lee, Su-Hwa', 'Koch, Brendan', 'Choi, Hyo-Jick']",Sci Rep,,,False
e594dcc4d1864621d24cc6ffbc70a88a5ae1207d,PMC,An assessment of the level of concern among hospital-based health-care workers regarding MERS outbreaks in Saudi Arabia,http://dx.doi.org/10.1186/s12879-016-2096-8,PMC5210292,28049440,CC BY,"BACKGROUND: Middle East Respiratory Syndrome (MERS) is caused by MERS coronavirus (MERS-CoV). More than 80% of reported cases have occurred in Saudi Arabia, with a mortality exceeding 50%. Health-care workers (HCWs) are at risk of acquiring and transmitting this virus, so the concerns of HCWs in Saudi Arabia regarding MERS were evaluated. METHODS: An anonymous, self-administered, previously validated questionnaire was given to 1031 HCWs at three tertiary hospitals in Saudi Arabia from October to December, 2014. Concerns regarding the disease, its severity and governmental efforts to contain it, as well as disease outcomes were assessed using 31 concern statements in five distinct domains. A total concern score was calculated for each HCW. Multiple regression analyses were used to identify predictors of high concern scores. RESULTS: The average age of participants was 37.1 ± 9.0 years, 65.8% were married and 59.1% were nurses. The majority of respondents (70.4%) felt at risk of contracting a MERS-CoV infection at work, 69.1% felt threatened if a colleague contracted MERS-CoV, 60.9% felt obliged to care for patients infected with MERS-CoV and 87.8% did not feel safe at work using standard precautions. In addition, 87.7% believed that the government should isolate patients with MERS in specialized hospitals, 73.7% agreed with travel restriction to and from areas affected by MERS and 65.3% agreed with avoiding inviting expatriates from such areas. After adjustment for covariates, high concern scores were significantly associated with being a Saudi national (p < 0.001), a non-physician (p < 0.001) and working in the central region (p < 0.001). CONCLUSIONS: The majority of respondents reported concern regarding MERS-CoV infection from exposure at work. The overall level of concern may be influenced by previous experience of MERS outbreaks and related cultural issues. The concerns of HCWs may affect their overall effectiveness in an outbreak and should be addressed by incorporating management strategies in outbreak planning.",2017 Jan 3,"['Abolfotouh, Mostafa A.', 'AlQarni, Ali A.', 'Al-Ghamdi, Suliman M.', 'Salam, Mahmoud', 'Al-Assiri, Mohammed H.', 'Balkhy, Hanan H.']",BMC Infect Dis,,,True
d58edd47f5a609373fc4fbfd0b3cb4dfcec173c3,PMC,BreathDx – molecular analysis of exhaled breath as a diagnostic test for ventilator–associated pneumonia: protocol for a European multicentre observational study,http://dx.doi.org/10.1186/s12890-016-0353-7,PMC5210294,28049457,CC BY,"BACKGROUND: The diagnosis of ventilator-associated pneumonia (VAP) remains time-consuming and costly, the clinical tools lack specificity and a bedside test to exclude infection in suspected patients is unavailable. Breath contains hundreds to thousands of volatile organic compounds (VOCs) that result from host and microbial metabolism as well as the environment. The present study aims to use breath VOC analysis to develop a model that can discriminate between patients who have positive cultures and who have negative cultures with a high sensitivity. METHODS/DESIGN: The Molecular Analysis of Exhaled Breath as Diagnostic Test for Ventilator-Associated Pneumonia (BreathDx) study is a multicentre observational study. Breath and bronchial lavage samples will be collected from 100 and 53 intubated and ventilated patients suspected of VAP. Breath will be analysed using Thermal Desorption – Gas Chromatography – Mass Spectrometry (TD-GC-MS). The primary endpoint is the accuracy of cross-validated prediction for positive respiratory cultures in patients that are suspected of VAP, with a sensitivity of at least 99% (high negative predictive value). DISCUSSION: To our knowledge, BreathDx is the first study powered to investigate whether molecular analysis of breath can be used to classify suspected VAP patients with and without positive microbiological cultures with 99% sensitivity. TRIAL REGISTRATION: UKCRN ID number 19086, registered May 2015; as well as registration at www.trialregister.nl under the acronym ‘BreathDx’ with trial ID number NTR 6114 (retrospectively registered on 28 October 2016).",2017 Jan 3,"['van Oort, Pouline M. P.', 'Nijsen, Tamara', 'Weda, Hans', 'Knobel, Hugo', 'Dark, Paul', 'Felton, Timothy', 'Rattray, Nicholas J. W.', 'Lawal, Oluwasola', 'Ahmed, Waqar', 'Portsmouth, Craig', 'Sterk, Peter J.', 'Schultz, Marcus J.', 'Zakharkina, Tetyana', 'Artigas, Antonio', 'Povoa, Pedro', 'Martin-Loeches, Ignacio', 'Fowler, Stephen J.', 'Bos, Lieuwe D. J.', None]",BMC Pulm Med,,,True
9a512204e9b43d11f12458baaa3db5cb71e5ae16,PMC,"De novo transcriptome assembly and characterization of nine tissues of Lonicera japonica to identify potential candidate genes involved in chlorogenic acid, luteolosides, and secoiridoid biosynthesis pathways",http://dx.doi.org/10.1007/s11418-016-1041-x,PMC5214891,27629269,CC BY,"Lonicera japonica is one of the most important medicinal plants with applications in traditional Chinese and Japanese medicine for thousands of years. Extensive studies on the constituents of L. japonica extracts have revealed an accumulation of pharmaceutically active metabolite classes, such as chlorogenic acid, luteolin and other flavonoids, and secoiridoids, which impart characteristic medicinal properties. Despite being a rich source of pharmaceutically active metabolites, little is known about the biosynthetic enzymes involved, and their expression profile across different tissues of L. japonica. In this study, we performed de novo transcriptome assembly for L. japonica, representing transcripts from nine different tissues. A total of 22 Gbps clean RNA-seq reads from nine tissues of L. japonica were used, resulting in 243,185 unigenes, with 99,938 unigenes annotated based on a homology search using blastx against the NCBI-nr protein database. Unsupervised principal component analysis and correlation studies using transcript expression data from all nine tissues of L. japonica showed relationships between tissues, explaining their association at different developmental stages. Homologs for all genes associated with chlorogenic acid, luteolin, and secoiridoid biosynthesis pathways were identified in the L. japonica transcriptome assembly. Expression of unigenes associated with chlorogenic acid was enriched in stems and leaf-2, unigenes from luteolin were enriched in stems and flowers, while unigenes from secoiridoid metabolic pathways were enriched in leaf-1 and shoot apex. Our results showed that different tissues of L. japonica are enriched with sets of unigenes associated with specific pharmaceutically important metabolic pathways and, therefore, possess unique medicinal properties. The present study will serve as a resource for future attempts for functional characterization of enzyme coding genes within key metabolic processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11418-016-1041-x) contains supplementary material, which is available to authorized users.",2017 Sep 14,"['Rai, Amit', 'Kamochi, Hidetaka', 'Suzuki, Hideyuki', 'Nakamura, Michimi', 'Takahashi, Hiroki', 'Hatada, Tomoki', 'Saito, Kazuki', 'Yamazaki, Mami']",J Nat Med,,,True
229bb9dc175fcc4d90e46d9ad90b67ab3e49a536,PMC,Virion Background and Efficiency of Virion Incorporation Determine Susceptibility of Simian Immunodeficiency Virus Env-Driven Viral Entry to Inhibition by IFITM Proteins,http://dx.doi.org/10.1128/JVI.01488-16,PMC5215347,27807233,CC BY,"Interferon-induced transmembrane proteins (IFITMs) can inhibit the cellular entry of several enveloped viruses, including simian immunodeficiency virus (SIV). The blockade of SIV by IFITMs is isolate specific, raising the question of which parameters impact sensitivity to IFITM. We show that the virion context in which SIV-Env is presented and the efficiency of virion incorporation determine Env susceptibility to inhibition by IFITMs. Thus, determinants other than the nature of the envelope protein can impact the IFITM sensitivity of viral entry. IMPORTANCE The host cell-encoded IFITM proteins can block viral entry and are an important component of the innate defenses against viral infection. However, the determinants controlling whether a virus is susceptible to blockade by IFITM proteins are incompletely understood. Our study shows that the amount of envelope proteins incorporated into virions as well as the nature of the virion particle itself can impact the sensitivity of viral entry to IFITMs. These results show for the first time that determinants other than the viral envelope protein can impact sensitivity to IFITM and have implications for the interpretation of previously published data on inhibition of viruses by IFITM proteins. Moreover, our findings might help to define the mechanism underlying the antiviral activity of IFITM proteins.",2017 Jan 3,"['Wrensch, Florian', 'Hoffmann, Markus', 'Gärtner, Sabine', 'Nehlmeier, Inga', 'Winkler, Michael', 'Pöhlmann, Stefan']",J Virol,,,True
99cbce9d58b005643a2402b10d8ec96ec8aea7c9,PMC,Improvement and Evaluation of Loop-Mediated Isothermal Amplification for Rapid Detection of Toxoplasma gondii Infection in Human Blood Samples,http://dx.doi.org/10.1371/journal.pone.0169125,PMC5215908,28056092,CC BY,"Loop-mediated isothermal amplification (LAMP), an attractive DNA amplification method, was developed as a valuable tool for the rapid detection of Toxoplasma gondii. In this study, species-specific LAMP primers were designed by targeting the AF146527 sequence, which was a conserved sequence of 200- to 300-fold repetitive 529 bp fragment of T.gondii. LAMP reaction system was optimized so that it could detect the minimal DNA sample such as a single tachyzoite or 10 copies of recombinant plasmid. No cross-reactivity was found when using DNA from other parasites as templates. Subsequently, a total of 200 human blood samples were directly investigated by two diagnostic methods, LAMP and conventional PCR. Fourteen of 200 (7%) samples were positive for Toxoplasma by LAMP (the primers developed in this study), whereas only 5 of 200 (2.5%) were proved positive by conventional PCR. The procedure of the LAMP assay was very simple, as the reaction would be carried out in a single tube under isothermal conditions at 64°C and the result would be read out with 1 h (as early as 35 min with loop primers). Thus, this method has the advantages of rapid amplification, simple operation, and easy detection and would be useful for rapid and reliable clinical diagnosis of acute toxoplasmosis, especially in developing countries.",2017 Jan 5,"['Sun, Xi-meng', 'Ji, Yong-sheng', 'Liu, Xian-yong', 'Xiang, Mei', 'He, Guang', 'Xie, Li', 'Suo, Jing-xia', 'Suo, Xun']",PLoS One,,,True
b9774fe2b5e6e752ff1e59bd6b2e46d7815b4a49,PMC,Outbreak of Middle East respiratory syndrome coronavirus in Saudi Arabia: a retrospective study,http://dx.doi.org/10.1186/s12879-016-2137-3,PMC5217314,28056850,CC BY,"BACKGROUND: The Middle East respiratory syndrome (MERS) is proposed to be a zoonotic disease. Dromedary camels have been implicated due to reports that some confirmed cases were exposed to camels. Risk factors for MERS coronavirus (MERS-CoV) infections in humans are incompletely understood. This study aimed to describe the demographic characteristics, mortality rate, clinical manifestations and comorbidities with confirmed cases of MERS-CoV. METHODS: Retrospective chart review were performed to identify all laboratory-confirmed cases of MERS-CoV in Saudi Arabia who reported to the Ministry of Health (MOH) of Saudi Arabia and WHO between April 23, 2014 and August 31, 2015. Patients’ charts were also reviewed for demographic information, mortality, comorbidities, clinical presentations, health care facility and presented with descriptive and comparative statistics using non parametric binomial test and Chi-square test. RESULTS: Confirmed cases of male patients (61.1%) exceeded those of female patients (38.9%). Infections among Saudi patients (62.6%) exceeded those among non-Saudi patients (37.4%; P = 0.001). The majority of the patients were aged 21–40 years (37.4%) or 41–60 years (35.8%); 43 (22.6%) were aged >61 years, and (8) 4.2% were aged 0–20 years. There was a difference in mortality between confirmed MERS-CoV cases (63.7% alive versus 36.3% dead cases, respectively). Furthermore, fever with cough and shortness of breath (SOB) (n = 39; 20.5%), fever with cough (n = 29; 15.3%), fever (n = 18; 9.5%), and fever with SOB (n = 13; 6.8%), were the most common clinical manifestations associated with confirmed MERS-CoV cases. CONCLUSION: MERS-CoV is considered an epidemic in Saudi Arabia. The results of the present study showed that the frequency of cases is higher among men than women, in Saudi patients than non-Saudi, and those between 21 to 60 years are most affected. Further studies are required to improve the surveillance associated with MERS-CoV to get definite and clear answers and better understanding of the MERS-CoV outbreak as well the source, and route of infection transmission in Saudi Arabia.",2017 Jan 5,"['Aleanizy, Fadilah Sfouq', 'Mohmed, Nahla', 'Alqahtani, Fulwah Y.', 'El Hadi Mohamed, Rania Ali']",BMC Infect Dis,,,True
914b5fc6d3984b981a1e36e545cc2a74e3fbd58a,PMC,Antiviral activity of animal venom peptides and related compounds,http://dx.doi.org/10.1186/s40409-016-0089-0,PMC5217322,28074089,CC BY,"Viruses exhibit rapid mutational capacity to trick and infect host cells, sometimes assisted through virus-coded peptides that counteract host cellular immune defense. Although a large number of compounds have been identified as inhibiting various viral infections and disease progression, it is urgent to achieve the discovery of more effective agents. Furthermore, proportionally to the great variety of diseases caused by viruses, very few viral vaccines are available, and not all are efficient. Thus, new antiviral substances obtained from natural products have been prospected, including those derived from venomous animals. Venoms are complex mixtures of hundreds of molecules, mostly peptides, that present a large array of biological activities and evolved to putatively target the biochemical machinery of different pathogens or host cellular structures. In addition, non-venomous compounds, such as some body fluids of invertebrate organisms, exhibit antiviral activity. This review provides a panorama of peptides described from animal venoms that present antiviral activity, thereby reinforcing them as important tools for the development of new therapeutic drugs.",2017 Jan 6,"['da Mata, Élida Cleyse Gomes', 'Mourão, Caroline Barbosa Farias', 'Rangel, Marisa', 'Schwartz, Elisabeth Ferroni']",J Venom Anim Toxins Incl Trop Dis,,,True
5a616c081f34c8ead17742a91a121ae167d77e17,PMC,A Review of Functional Motifs Utilized by Viruses,http://dx.doi.org/10.3390/proteomes4010003,PMC5217368,28248213,CC BY,"Short linear motifs (SLiM) are short peptides that facilitate protein function and protein-protein interactions. Viruses utilize these motifs to enter into the host, interact with cellular proteins, or egress from host cells. Studying functional motifs may help to predict protein characteristics, interactions, or the putative cellular role of a protein. In virology, it may reveal aspects of the virus tropism and help find antiviral therapeutics. This review highlights the recent understanding of functional motifs utilized by viruses. Special attention was paid to the function of proteins harboring these motifs, and viruses encoding these proteins. The review highlights motifs involved in (i) immune response and post-translational modifications (e.g., ubiquitylation, SUMOylation or ISGylation); (ii) virus-host cell interactions, including virus attachment, entry, fusion, egress and nuclear trafficking; (iii) virulence and antiviral activities; (iv) virion structure; and (v) low-complexity regions (LCRs) or motifs enriched with residues (Xaa-rich motifs).",2016 Jan 21,"Sobhy, Haitham",Proteomes,,,True
82009d2b6ae6ffc4372b1d4ecc9cfa7037cb8aa0,PMC,A Review of Functional Motifs Utilized by Viruses,http://dx.doi.org/10.3390/proteomes4010003,PMC5217368,28248213,CC BY,"Short linear motifs (SLiM) are short peptides that facilitate protein function and protein-protein interactions. Viruses utilize these motifs to enter into the host, interact with cellular proteins, or egress from host cells. Studying functional motifs may help to predict protein characteristics, interactions, or the putative cellular role of a protein. In virology, it may reveal aspects of the virus tropism and help find antiviral therapeutics. This review highlights the recent understanding of functional motifs utilized by viruses. Special attention was paid to the function of proteins harboring these motifs, and viruses encoding these proteins. The review highlights motifs involved in (i) immune response and post-translational modifications (e.g., ubiquitylation, SUMOylation or ISGylation); (ii) virus-host cell interactions, including virus attachment, entry, fusion, egress and nuclear trafficking; (iii) virulence and antiviral activities; (iv) virion structure; and (v) low-complexity regions (LCRs) or motifs enriched with residues (Xaa-rich motifs).",2016 Jan 21,"Sobhy, Haitham",Proteomes,,,False
7e4905089dd52ffd586f780d272e2cd951457196,PMC,Understanding the early dynamics of the 2014 porcine epidemic diarrhea virus (PEDV) outbreak in Ontario using the incidence decay and exponential adjustment (IDEA) model,http://dx.doi.org/10.1186/s12917-016-0922-2,PMC5217418,28056953,CC BY,"BACKGROUND: The United States swine industry was first confronted with porcine epidemic diarrhea virus (PEDV) in 2013. In young pigs, the virus is highly pathogenic and the associated morbidity and mortality has a significant negative impact on the swine industry. We have applied the IDEA model to better understand the 2014 PEDV outbreak in Ontario, Canada. Using our simple, 2-parameter IDEA model, we have evaluated the early epidemic dynamics of PEDV on Ontario swine farms. RESULTS: We estimated the best-fit R(0) and control parameter (d) for the between farm transmission component of the outbreak by fitting the model to publically available cumulative incidence data. We used maximum likelihood to compare model fit estimates for different combinations of the R(0) and d parameters. Using our initial findings from the iterative fitting procedure, we projected the time course of the epidemic using only a subset of the early epidemic data. The IDEA model projections showed excellent agreement with the observed data based on a 7-day generation time estimate. The best-fit estimate for R(0) was 1.87 (95% CI: 1.52 – 2.34) and for the control parameter (d) was 0.059 (95% CI: 0.022 – 0.117). Using data from the first three generations of the outbreak, our iterative fitting procedure suggests that R(0) and d had stabilized sufficiently to project the time course of the outbreak with reasonable accuracy. CONCLUSIONS: The emergence and spread of PEDV represents an important agricultural emergency. The virus presents a significant ongoing threat to the Canadian swine industry. Developing an understanding of the important epidemiological characteristics and disease transmission dynamics of a novel pathogen such as PEDV is critical for helping to guide the implementation of effective, efficient, and economically feasible disease control and prevention strategies that are able to help decrease the impact of an outbreak.",2017 Jan 5,"['Greer, Amy L.', 'Spence, Kelsey', 'Gardner, Emma']",BMC Vet Res,,,True
4e45854eace4e5bb9255ad31f7425545f931f3fe,PMC,Pseudorabies virus infection (Aujeszky’s disease) in an Iberian lynx (Lynx pardinus) in Spain: a case report,http://dx.doi.org/10.1186/s12917-016-0938-7,PMC5217549,28056966,CC BY,"BACKGROUND: The only natural hosts of Pseudorabies virus (PRV) are members of the family Suidae (Sus scrofa scrofa). In species other than suids infection is normally fatal. In these mammals, including carnivores, PRV typically causes serious neurologic disease. The endangered Iberian lynx (Lynx pardinus) is a wild feline endemic to south-western Europe (Iberian Peninsula). The Iberian lynx was found to be the world’s most endangered felid species in 2002. In wild felines, PRV infection has only been previously reported once in a Florida panther in 1994. No seropositive lynxes have ever been found, nor has PRV been detected in dead Iberian lynxes to date. CASE PRESENTATION: We describe the first reported case of pseudorabies in an Iberian lynx (Lynx pardinus). Pseudorabies was diagnosed in a young wild Iberian lynx from Extremadura (SW Spain) by histopathological examination, immunohistochemistry, polymerase chain reaction (PCR) and sequence analysis. Gross lesions included alopecia of the ventral neck, bloody gastro-intestinal contents and congestion of the brain. Histopathological analysis showed a moderate nonsuppurative meningoencephalitis with diffuse areas of demyelination, necrotizing gastritis and enteritis of the small intestine. Pseudorabies virus (PRV) antigen was found in neuronal and non-neuronal cells of the brain, tonsils, and gastric glandular epithelial cells by immunohistochemical analysis. The presence of the virus in the brain was confirmed by nested PCR. The sequence analysis of the 146 bp fragment (from the viral glycoprotein B gene) showed that the amplified sequence matched (with 100% identity) the PRV genome. Furthermore, specific DNA from glycoprotein D and E encoding-genes was detected by conventional and real-time PCR, respectively, confirming the latter that this infection was produced by a wild-type PRV strain. CONCLUSIONS: This study supports the suspicion that PRV could infect the Iberian lynx. The detection of PRV in a dead Iberian lynx suggests that the virus may have a negative impact on the survival of endangered lynxes in the wild. However, because this is the first verified instance of lynx mortality resulting from pseudorabies, its true impact on the population is unknown. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0938-7) contains supplementary material, which is available to authorized users.",2017 Jan 5,"['Masot, A. Javier', 'Gil, María', 'Risco, David', 'Jiménez, Olga M.', 'Núñez, José I.', 'Redondo, Eloy']",BMC Vet Res,,,True
6aea4f0b8aaacfac3d0d3b49bd7558481da9b03f,PMC,One-Pot Reverse Transcriptional Loop-Mediated Isothermal Amplification (RT-LAMP) for Detecting MERS-CoV,http://dx.doi.org/10.3389/fmicb.2016.02166,PMC5220095,28119682,CC BY,"Due to the limitation of rapid development of specific antiviral drug or vaccine for novel emerging viruses, an accurate and rapid diagnosis is a key to manage the virus spread. We developed an efficient and rapid method with high specificity for the Middle East Respiratory Syndrome coronavirus (MERS-CoV), based on one-pot reverse transcription loop-mediated isothermal amplification (one-pot RT-LAMP). A set of six LAMP primers [F3, B3, FIP, BIP, LF (Loop-F), and LB (Loop-B)] were designed using the sequence of nucleocapsid (N) gene with optimized RT-LAMP enzyme conditions: 100 U M-MLV RTase and 4 U Bst polymerase, implying that the reaction was able to detect four infectious viral genome copies of MERS-CoV within a 60 min reaction time period. Significantly, EvaGreen dye has better signal read-out properties in one-pot RT-LAMP reaction and is more compatible with DNA polymerase than SYBR green I. Isothermally amplified specific N genes were further evaluated using field-deployable microchamber devices, leading to the specific identification of as few as 0.4 infectious viral genome copies, with no cross-reaction to the other acute respiratory disease viruses, including influenza type A (H1N1 and H3N2), type B, human coronavirus 229E, and human metapneumovirus. This sensitive, specific and feasible method provides a large-scale technical support in emergencies, and is also applied as a sample-to-detection module in Point of Care Testing devices.",2017 Jan 9,"['Lee, Se Hee', 'Baek, Yun Hee', 'Kim, Yang-Hoon', 'Choi, Young-Ki', 'Song, Min-Suk', 'Ahn, Ji-Young']",Front Microbiol,,,True
f7f482ba4aaa3ef0d620d9aad8c9635f88806d8e,PMC,The autophagy elongation complex (ATG5-12/16L1) positively regulates HCV replication and is required for wild-type membranous web formation,http://dx.doi.org/10.1038/srep40351,PMC5220323,28067309,CC BY,"Hepatitis C virus (HCV) infection induces intracellular membrane rearrangements, thus forming a membranous web (MW) in which HCV replication and assembly occur. The HCV-induced MW is primarily composed of double membrane vesicles (DMVs) transfused by multi-membrane vesicles. The autophagy machinery has been proposed to participate in the formation of such vesicles. However, no clear evidence has been found linking autophagy to the formation of these DMVs. In this study, we evaluated the role of the autophagy elongation complex (ATG5-12/16L1) in HCV replication and MW formation. Using a dominant negative form of ATG12 and an siRNA approach, we demonstrated that the ATG5-12 conjugate, but not LC3-II formation, is crucial for efficient viral replication. Furthermore, purification of HCV MW revealed the presence of ATG5-12 and ATG16L1 along with HCV nonstructural proteins. Interestingly, LC3 was not recruited along with the elongation complex to the site of viral replication. Finally, inhibition of the elongation complex, but not LC3, greatly impaired the formation of the wild-type MW phenotype. To our knowledge, this study provides the first evidence of the involvement of autophagy proteins in the formation of wild-type MWs.",2017 Jan 9,"['Fahmy, Ahmed M.', 'Labonté, Patrick']",Sci Rep,,,True
f130e5346baa10d030f853af0b490818527a2508,PMC,The autophagy elongation complex (ATG5-12/16L1) positively regulates HCV replication and is required for wild-type membranous web formation,http://dx.doi.org/10.1038/srep40351,PMC5220323,28067309,CC BY,"Hepatitis C virus (HCV) infection induces intracellular membrane rearrangements, thus forming a membranous web (MW) in which HCV replication and assembly occur. The HCV-induced MW is primarily composed of double membrane vesicles (DMVs) transfused by multi-membrane vesicles. The autophagy machinery has been proposed to participate in the formation of such vesicles. However, no clear evidence has been found linking autophagy to the formation of these DMVs. In this study, we evaluated the role of the autophagy elongation complex (ATG5-12/16L1) in HCV replication and MW formation. Using a dominant negative form of ATG12 and an siRNA approach, we demonstrated that the ATG5-12 conjugate, but not LC3-II formation, is crucial for efficient viral replication. Furthermore, purification of HCV MW revealed the presence of ATG5-12 and ATG16L1 along with HCV nonstructural proteins. Interestingly, LC3 was not recruited along with the elongation complex to the site of viral replication. Finally, inhibition of the elongation complex, but not LC3, greatly impaired the formation of the wild-type MW phenotype. To our knowledge, this study provides the first evidence of the involvement of autophagy proteins in the formation of wild-type MWs.",2017 Jan 9,"['Fahmy, Ahmed M.', 'Labonté, Patrick']",Sci Rep,,,False
80514d274dfaa180080c8eb0bb261c0af5c95c49,PMC,Development of a Recombinase Polymerase Amplification Assay for Detection of Epidemic Human Noroviruses,http://dx.doi.org/10.1038/srep40244,PMC5220337,28067278,CC BY,"Human norovirus is a leading cause of viral gastroenteritis worldwide. Rapid detection could facilitate control, however widespread point-of-care testing is infrequently done due to the lack of robust and portable methods. Recombinase polymerase amplification (RPA) is a novel isothermal method which rapidly amplifies and detects nucleic acids using a simple device in near real-time. An RT-RPA assay targeting a recent epidemic human norovirus strain (GII.4 New Orleans) was developed and evaluated in this study. The assay successfully detected purified norovirus RNA from multiple patient outbreak isolates and had a limit of detection of 3.40 ± 0.20 log(10) genomic copies (LGC), which is comparable to most other reported isothermal norovirus amplification methods. The assay also detected norovirus in directly boiled stool, and displayed better resistance to inhibitors than a commonly used RT-qPCR assay. The assay was specific, as it did not amplify genomes from 9 non-related enteric viruses and bacteria. The assay detected norovirus in some samples in as little as 6 min, and the entire detection process can be performed in less than 30 min. The reported RT-RPA method shows promise for sensitive point-of-care detection of epidemic human norovirus, and is the fastest human norovirus amplification method to date.",2017 Jan 9,"['Moore, Matthew D.', 'Jaykus, Lee-Ann']",Sci Rep,,,True
50df576e673f129424832b55011ea30334063e47,PMC,Development of a Recombinase Polymerase Amplification Assay for Detection of Epidemic Human Noroviruses,http://dx.doi.org/10.1038/srep40244,PMC5220337,28067278,CC BY,"Human norovirus is a leading cause of viral gastroenteritis worldwide. Rapid detection could facilitate control, however widespread point-of-care testing is infrequently done due to the lack of robust and portable methods. Recombinase polymerase amplification (RPA) is a novel isothermal method which rapidly amplifies and detects nucleic acids using a simple device in near real-time. An RT-RPA assay targeting a recent epidemic human norovirus strain (GII.4 New Orleans) was developed and evaluated in this study. The assay successfully detected purified norovirus RNA from multiple patient outbreak isolates and had a limit of detection of 3.40 ± 0.20 log(10) genomic copies (LGC), which is comparable to most other reported isothermal norovirus amplification methods. The assay also detected norovirus in directly boiled stool, and displayed better resistance to inhibitors than a commonly used RT-qPCR assay. The assay was specific, as it did not amplify genomes from 9 non-related enteric viruses and bacteria. The assay detected norovirus in some samples in as little as 6 min, and the entire detection process can be performed in less than 30 min. The reported RT-RPA method shows promise for sensitive point-of-care detection of epidemic human norovirus, and is the fastest human norovirus amplification method to date.",2017 Jan 9,"['Moore, Matthew D.', 'Jaykus, Lee-Ann']",Sci Rep,,,False
3eb1bcee33c1121bd5307cf9a0c91f2510f4f79f,PMC,Comparative interactomics for virus–human protein–protein interactions: DNA viruses versus RNA viruses,http://dx.doi.org/10.1002/2211-5463.12167,PMC5221455,28097092,CC BY,"Viruses are obligatory intracellular pathogens and completely depend on their hosts for survival and reproduction. The strategies adopted by viruses to exploit host cell processes and to evade host immune systems during infections may differ largely with the type of the viral genetic material. An improved understanding of these viral infection mechanisms is only possible through a better understanding of the pathogen–host interactions (PHIs) that enable viruses to enter into the host cells and manipulate the cellular mechanisms to their own advantage. Experimentally‐verified protein–protein interaction (PPI) data of pathogen–host systems only became available at large scale within the last decade. In this study, we comparatively analyzed the current PHI networks belonging to DNA and RNA viruses and their human host, to get insights into the infection strategies used by these viral groups. We investigated the functional properties of human proteins in the PHI networks, to observe and compare the attack strategies of DNA and RNA viruses. We observed that DNA viruses are able to attack both human cellular and metabolic processes simultaneously during infections. On the other hand, RNA viruses preferentially interact with human proteins functioning in specific cellular processes as well as in intracellular transport and localization within the cell. Observing virus‐targeted human proteins, we propose heterogeneous nuclear ribonucleoproteins and transporter proteins as potential antiviral therapeutic targets. The observed common and specific infection mechanisms in terms of viral strategies to attack human proteins may provide crucial information for further design of broad and specific next‐generation antiviral therapeutics.",2017 Jan 4,"['Durmuş, Saliha', 'Ülgen, Kutlu Ö.']",FEBS Open Bio,,,True
6f0c490d80ef3e7032010a057baa96d4d45ababc,PMC,Behavioural change models for infectious disease transmission: a systematic review (2010–2015),http://dx.doi.org/10.1098/rsif.2016.0820,PMC5221530,28003528,CC BY,"We review behavioural change models (BCMs) for infectious disease transmission in humans. Following the Cochrane collaboration guidelines and the PRISMA statement, our systematic search and selection yielded 178 papers covering the period 2010–2015. We observe an increasing trend in published BCMs, frequently coupled to (re)emergence events, and propose a categorization by distinguishing how information translates into preventive actions. Behaviour is usually captured by introducing information as a dynamic parameter (76/178) or by introducing an economic objective function, either with (26/178) or without (37/178) imitation. Approaches using information thresholds (29/178) and exogenous behaviour formation (16/178) are also popular. We further classify according to disease, prevention measure, transmission model (with 81/178 population, 6/178 metapopulation and 91/178 individual-level models) and the way prevention impacts transmission. We highlight the minority (15%) of studies that use any real-life data for parametrization or validation and note that BCMs increasingly use social media data and generally incorporate multiple sources of information (16/178), multiple types of information (17/178) or both (9/178). We conclude that individual-level models are increasingly used and useful to model behaviour changes. Despite recent advancements, we remain concerned that most models are purely theoretical and lack representative data and a validation process.",2016 Dec,"['Verelst, Frederik', 'Willem, Lander', 'Beutels, Philippe']",J R Soc Interface,,,True
b8a1d1bdea4cc683b11719ab5e20e2b85f7cb08e,PMC,Enteric Pathogens and Coinfections in Foals with and without Diarrhea,http://dx.doi.org/10.1155/2016/1512690,PMC5223019,28116290,CC BY,"Diarrhea is a major clinical problem affecting foals up to 3 months of age. The aim of this study was to identify enteric microorganisms involved in monoinfections and coinfections and the associated virulence factors in healthy and diarrheic foals. Diarrheic (D) (n = 56) and nondiarrheic (ND) foals (n = 60) up to three months of age were studied. Fecal samples were analyzed for identification of infectious agents (microbiological culturing, molecular techniques, and microscopic analyses). Escherichia coli fimH (30% versus 25%), Salmonella spp. (25% versus 7%), Strongyloides westeri (25% versus 25%), Clostridium perfringens type A (21% versus 10%), E. coli ag43 (20% versus 35%), Strongylus (11% versus 18%), and vapA-positive Rhodococcus equi (5% versus 2%) were the most frequent enteric pathogens detected in D and ND foals, respectively. The frequency of toxin A-positive C. perfringens was significantly increased in the D (p = 0.033) compared with the ND animals. R. equi strains harboring virulent plasmids were also identified (VapA 85-kb type I and VapA 87-kb type I) in D and ND foals. Coinfections were observed in 46% of the D and 33% of the ND foals. Our results demonstrate the great diversity of enteric pathogens, virulence factors, and coinfections involved in enteric infections of foals.",2016 Dec 27,"['Olivo, Giovane', 'Lucas, Thays Mizuki', 'Borges, Alexandre Secorun', 'Silva, Rodrigo Otávio Silveira', 'Lobato, Francisco Carlos Faria', 'Siqueira, Amanda Keller', 'da Silva Leite, Domingos', 'Brandão, Paulo Eduardo', 'Gregori, Fábio', 'de Oliveira-Filho, José Paes', 'Takai, Shinji', 'Ribeiro, Márcio Garcia']",Biomed Res Int,,,True
e0359b1b4c6d229299cb7b9f149bc9b943a2077f,PMC,Sporadic cases of adult measles: a research article,http://dx.doi.org/10.1186/s13104-017-2374-6,PMC5223409,28069071,CC BY,"BACKGROUND: Measles caused by a paramyxovirus, characterized by fever, malaise, cough, coryza conjunctivitis, a maculopapular rash is known to result in pneumonia, encephalitis and death. Fatal cases of measles in Sri Lanka are rare after implementation of the National Immunization Programme in 1984. Thereafter 0.1% case fatality rate was observed during October 1999–June 2000 which is a very low figure compared to other regional countries. Immunization guidelines were further revised in 2001, 2011 and in 2012 when additional immunization was recommended to age group 4–21 years; who are likely to have inadequate immunization, in order to achieve elimination of Measles by 2020. However, in 2013–2014, 4690 cases were reported and the majority were children less than 1 year of age. The occurrence in adults is hard to retrieve in published epidemiological reports, however had been 38% (out of 1008 patients) in the 3rd quarter of 2013. During this outbreak 73/101 (72%) reported from the North Central Province of Sri Lanka had been more than 12 years of age with 50% being more than 29 years. 14 Sri lankan adult patients [median age 32 years (range 25–48)] who presented sporadically from June 2014 to March 2016, with confirmed measles infection were enrolled retrospectively after informed consent. Details with regards to their clinical presentation, immunization and other relevant areas were collected using an interviewer administered questionnaire or using patient management records. RESULTS: The patients presented with high fever, headache, severe body aches, sore throat, dry cough, intense tearing, red eyes and posterior cervical lymphadenopathy over 3–5 days duration. Later they developed discrete maculopapular rash helping the diagnosis. They had a variable degree of leucopenia, lymphocytosis, thrombocytopenia and derangements in the liver functions mimicking any other acute febrile illnesses such as dengue, chikungunya, leptospirosis or Zika virus infection. CONCLUSION: At least a 3–5 day delay in the diagnosis was observed (even after the appearance of the rash in some patients), due to non-awareness of its occurrence, unfamiliarity of measles in adults, non-specific nature of the illness and non-availability of rapid diagnostics, risking transmission to the immune-compromised or non-immune staff or patients. Identification of the source of infection in these sporadic adult cases and their virologic surveillance and molecular epidemiology will be important to interrupt the transmission and to achieve the targeted elimination of measles from Sri Lanka by 2020.",2017 Jan 10,"['Premaratna, Ranjan', 'Luke, Nathasha', 'Perera, Harsha', 'Gunathilake, Mahesh', 'Amarasena, Pubudu', 'Chandrasena, T. G. A. Nilmini']",BMC Res Notes,,,True
7cd8d3fec1f3a8251b75a50aad856e1b5526de83,PMC,Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations,http://dx.doi.org/10.1186/s13756-016-0149-9,PMC5223492,28078082,CC BY,"Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13756-016-0149-9) contains supplementary material, which is available to authorized users.",2017 Jan 10,"['Storr, Julie', 'Twyman, Anthony', 'Zingg, Walter', 'Damani, Nizam', 'Kilpatrick, Claire', 'Reilly, Jacqui', 'Price, Lesley', 'Egger, Matthias', 'Grayson, M. Lindsay', 'Kelley, Edward', 'Allegranzi, Benedetta', None]",Antimicrob Resist Infect Control,,,True
c14ce2c27ca770924c1ca4a4fef0fa5b532f73c1,PMC,Cluster randomised controlled trial to examine medical mask use as source control for people with respiratory illness,http://dx.doi.org/10.1136/bmjopen-2016-012330,PMC5223715,28039289,CC BY,"RATIONALE: Medical masks are commonly used by sick individuals with influenza-like illness (ILI) to prevent spread of infections to others, but clinical efficacy data are absent. OBJECTIVE: Determine whether medical mask use by sick individuals with ILI protects well contacts from related respiratory infections. SETTING: 6 major hospitals in 2 districts of Beijing, China. DESIGN: Cluster randomised controlled trial. PARTICIPANTS: 245 index cases with ILI. INTERVENTION: Index cases with ILI were randomly allocated to medical mask (n=123) and control arms (n=122). Since 43 index cases in the control arm also used a mask during the study period, an as-treated post hoc analysis was performed by comparing outcomes among household members of index cases who used a mask (mask group) with household members of index cases who did not use a mask (no-mask group). MAIN OUTCOME MEASURE: Primary outcomes measured in household members were clinical respiratory illness, ILI and laboratory-confirmed viral respiratory infection. RESULTS: In an intention-to-treat analysis, rates of clinical respiratory illness (relative risk (RR) 0.61, 95% CI 0.18 to 2.13), ILI (RR 0.32, 95% CI 0.03 to 3.13) and laboratory-confirmed viral infections (RR 0.97, 95% CI 0.06 to 15.54) were consistently lower in the mask arm compared with control, although not statistically significant. A post hoc comparison between the mask versus no-mask groups showed a protective effect against clinical respiratory illness, but not against ILI and laboratory-confirmed viral respiratory infections. CONCLUSIONS: The study indicates a potential benefit of medical masks for source control, but is limited by small sample size and low secondary attack rates. Larger trials are needed to confirm efficacy of medical masks as source control. TRIAL REGISTRATION NUMBER: ACTRN12613000852752; Results.",2016 Dec 30,"['MacIntyre, Chandini Raina', 'Zhang, Yi', 'Chughtai, Abrar Ahmad', 'Seale, Holly', 'Zhang, Daitao', 'Chu, Yanhui', 'Zhang, Haiyan', 'Rahman, Bayzidur', 'Wang, Quanyi']",BMJ Open,,,True
6fa9d1fe1938a48f36f837cec479925de3a69b64,PMC,IL-1β is a key cytokine that induces trypsin upregulation in the influenza virus–cytokine–trypsin cycle,http://dx.doi.org/10.1007/s00705-016-3093-3,PMC5225228,27714503,CC BY,"Severe influenza is characterized by a cytokine storm, and the influenza virus–cytokine–trypsin cycle is one of the important mechanisms of viral multiplication and multiple organ failure. The aim of this study was to define the key cytokine(s) responsible for trypsin upregulation. Mice were infected with influenza virus strain A/Puerto Rico/8/34 (H1N1) or treated individually or with a combination of interleukin-1β, interleukin-6, and tumor necrosis factor α. The levels of these cytokines and trypsin in the lungs were monitored. The neutralizing effects of anti-IL-1β antibodies on cytokine and trypsin expression in human A549 cells and lung inflammation in the infected mice were examined. Infection induced interleukin-1β, interleukin-6, tumor necrosis factor α, and ectopic trypsin in mouse lungs in a dose- and time-dependent manner. Intraperitoneal administration of interleukin-1β combined with other cytokines tended to upregulate trypsin and cytokine expression in the lungs, but the combination without interleukin-1β did not induce trypsin. In contrast, incubation of A549 cells with interleukin-1β alone induced both cytokines and trypsin, and anti-interleukin-1β antibody treatment abrogated these effects. Administration of the antibody in the infected mice reduced lung inflammation area. These findings suggest that IL-1β plays a key role in trypsin upregulation and has a pathological role in multiple organ failure.",2017 Oct 6,"['Indalao, I. L.', 'Sawabuchi, T.', 'Takahashi, E.', 'Kido, H.']",Arch Virol,,,True
64536ef4a2d1df35305df73397d745ae55be8d47,PMC,Single- and multiple viral respiratory infections in children: disease and management cannot be related to a specific pathogen,http://dx.doi.org/10.1186/s12879-016-2118-6,PMC5225597,28077074,CC BY,"BACKGROUND: The number of viral pathogens associated with pediatric acute respiratory tract infection (ARI) has grown since the introduction of reverse transcription real-time polymerase chain reaction (RT-PCR) assays. Multiple viruses are detected during a single ARI episode in approximately a quarter of all cases. The clinical relevance of these multiple detections is unclear, as is the role of the individual virus. We therefore investigated the correlation between clinical data and RT-PCR results in children with single- and multiple viral ARI. METHODS: Data from children with ARI were prospectively collected during two winter seasons. RT-PCR testing for 15 viruses was performed in 560 ARI episodes. In the patients with a single-viral etiology, clinical data, laboratory findings, patient management- and outcome data were compared between the different viruses. With this information, we compared data from children of whom RT-PCR data were negative, with children with single- and multiple viral positive results. RESULTS: The viral detection rate was 457/560 (81.6%) of which 331/560 (59.1%) were single infections and 126/560 (22.5%) were multiple infections. In single viral infections, some statistically significant differences in demographics, clinical findings, disease severity and outcome were found between children with different viral etiologies. However, no clinically recognizable pattern was established to be virus-specific. In a multivariate analysis, the only variables that were correlated with longer hospital stay were the use of oxygen and nebulizer therapy, irrespective of the viral pathogen. Children with RT-PCR positive test results had a significant higher disease severity, fever, length of hospital stay, days of extra oxygen supply, and days of antibiotic treatment than children with a negative RT-PCR test result. For children with single- versus children with multiple positive RT-PCR test results, these differences were not significant. CONCLUSIONS: Disease (severity), management and outcome in pediatric ARI are not associated with a specific virus. Single- and multiple viral ARI do not significantly differ with regard to clinical outcome and patient management. For general pediatrics, RT-PCR assays should be restricted to pathogens for which therapy is available or otherwise may have clinical consequences. Further research with an extended panel of RT-PCR assays and a larger number of inclusions is necessary to further validate our findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-2118-6) contains supplementary material, which is available to authorized users.",2017 Jan 11,"['Wishaupt, Jérôme O.', 'van der Ploeg, Tjeerd', 'de Groot, Ronald', 'Versteegh, Florens G. A.', 'Hartwig, Nico G.']",BMC Infect Dis,,,True
b360dd33baf9170084ca4b452e13e92d3bbdefee,PMC,When Viruses Don’t Go Viral: The Importance of Host Phylogeographic Structure in the Spatial Spread of Arenaviruses,http://dx.doi.org/10.1371/journal.ppat.1006073,PMC5226678,28076397,CC BY,"Many emerging infections are RNA virus spillovers from animal reservoirs. Reservoir identification is necessary for predicting the geographic extent of infection risk, but rarely are taxonomic levels below the animal species considered as reservoir, and only key circumstances in nature and methodology allow intrinsic virus-host associations to be distinguished from simple geographic (co-)isolation. We sampled and genetically characterized in detail a contact zone of two subtaxa of the rodent Mastomys natalensis in Tanzania. We find two distinct arenaviruses, Gairo and Morogoro virus, each spatially confined to a single M. natalensis subtaxon, only co-occurring at the contact zone’s centre. Inter-subtaxon hybridization at this centre and a continuum of quality habitat for M. natalensis show that both viruses have the ecological opportunity to spread into the other substaxon’s range, but do not, strongly suggesting host-intrinsic barriers. Such barriers could explain why human cases of another M. natalensis-borne arenavirus, Lassa virus, are limited to West Africa.",2017 Jan 11,"['Gryseels, Sophie', 'Baird, Stuart J. E.', 'Borremans, Benny', 'Makundi, Rhodes', 'Leirs, Herwig', 'Goüy de Bellocq, Joëlle']",PLoS Pathog,,,True
28f3721175c93e3f6ca2eea98d30ac3ea45a5f68,PMC,When Viruses Don’t Go Viral: The Importance of Host Phylogeographic Structure in the Spatial Spread of Arenaviruses,http://dx.doi.org/10.1371/journal.ppat.1006073,PMC5226678,28076397,CC BY,"Many emerging infections are RNA virus spillovers from animal reservoirs. Reservoir identification is necessary for predicting the geographic extent of infection risk, but rarely are taxonomic levels below the animal species considered as reservoir, and only key circumstances in nature and methodology allow intrinsic virus-host associations to be distinguished from simple geographic (co-)isolation. We sampled and genetically characterized in detail a contact zone of two subtaxa of the rodent Mastomys natalensis in Tanzania. We find two distinct arenaviruses, Gairo and Morogoro virus, each spatially confined to a single M. natalensis subtaxon, only co-occurring at the contact zone’s centre. Inter-subtaxon hybridization at this centre and a continuum of quality habitat for M. natalensis show that both viruses have the ecological opportunity to spread into the other substaxon’s range, but do not, strongly suggesting host-intrinsic barriers. Such barriers could explain why human cases of another M. natalensis-borne arenavirus, Lassa virus, are limited to West Africa.",2017 Jan 11,"['Gryseels, Sophie', 'Baird, Stuart J. E.', 'Borremans, Benny', 'Makundi, Rhodes', 'Leirs, Herwig', 'Goüy de Bellocq, Joëlle']",PLoS Pathog,,,False
409834df62ccb98e2497be0afcb86af5b5f815a4,PMC,When Viruses Don’t Go Viral: The Importance of Host Phylogeographic Structure in the Spatial Spread of Arenaviruses,http://dx.doi.org/10.1371/journal.ppat.1006073,PMC5226678,28076397,CC BY,"Many emerging infections are RNA virus spillovers from animal reservoirs. Reservoir identification is necessary for predicting the geographic extent of infection risk, but rarely are taxonomic levels below the animal species considered as reservoir, and only key circumstances in nature and methodology allow intrinsic virus-host associations to be distinguished from simple geographic (co-)isolation. We sampled and genetically characterized in detail a contact zone of two subtaxa of the rodent Mastomys natalensis in Tanzania. We find two distinct arenaviruses, Gairo and Morogoro virus, each spatially confined to a single M. natalensis subtaxon, only co-occurring at the contact zone’s centre. Inter-subtaxon hybridization at this centre and a continuum of quality habitat for M. natalensis show that both viruses have the ecological opportunity to spread into the other substaxon’s range, but do not, strongly s